Diet therapy and metabolic control among Chilean adults with a neonatal diagnosis of Phenylketonuria

Abstract Phenylketonuria (PKU) is an autosomal recessive defect affecting the metabolic pathway of phenylalanine (Phe), causing hyperphenylalaninemia and neurotoxicity. Diagnosis must occur in the neonatal period and treatment should begin as early as possible. Evidence implies that treatment adherence declines as age advances. The aim was to describe the diet of a subgroup of Chilean adults with PKU currently in follow-up. Fifty-three subjects (49% women) followed up between January 2021 to April 2023 were considered. The concentration of Phe (PheC) in dried blood spots measured by fluorometry and 24-hour dietary recalls were analyzed. The median PheC of the sample was 438µmol/L (interquartile range(IQR):351-585µmol/L). A protein intake of 1.35±0.3 gr/Kg/d was observed of which 87% came from the protein substitute without Phe. Participants had a median Phe intake of 459mg/d (IQR:327-976) and 13.1g/d of fiber intake. Most participants, 51% and 92% reported consuming fruits and vegetables, respectively, and 32% consumed Low-Protein foods. Regarding micronutrients, all participants exceeded 90% adequacy according to recommendations. For vitamin-D and vitamin-B12, 100% is provided by the protein substitute. According to our results, it is mandatory to establish transition programs toward adulthood, to constantly maintain good metabolic control, and to adapt diet therapy to their new lifestyle.

Optimization of mRNA extraction from human nasal mucosa biopsies for gene expression profile analysis by qRT-PCR.

Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) is the gold-standard method for analyzing modifications in gene expression in cells and tissues. However, large quantities of high-quality RNA samples are needed for analyzing the expression of multiple genes from one human tissue sample. Here, we provide an optimized protocol for extracting large amounts of RNA from human nasal mucosal biopsies. The quality and quantity of samples were sufficient for qRT-PCR analyses of the expressions of various genes, in duplicate. In contrast to other protocols, we optimized RNA isolation to increase the amount from nasal biopsy samples for analyses of multiple genes. In most previous publications, expressions of only one or a few genes, including housekeeping genes, were analyzed because the amount of biological material was small. We were able to improve our protocol with respect to the yield and quality of RNA. This is likely to produce better results from molecular analyses of very small biopsy samples of human nasal mucosa.

Future therapeutic strategies for olfactory disorders: electrical stimulation, stem cell therapy, and transplantation of olfactory epithelium-an overview.

Olfactory disorders may be temporary or permanent and can have various causes. Currently, many COVID-19 patients report a reduced or complete loss of olfactory function. A wide range of treatment options have been investigated in the past, such as olfactory training, acupuncture, medical therapy, transcranial magnetic stimulation, or surgical excision of olfactory epithelium, e.g., in severe qualitative smell disorders. The development of a bioelectric nose, e.g., in connection with direct electrical stimulation or transplantation of olfactory epithelium or stem cells, represent treatment options of the future. The basis of these developments and the state of knowledge is discussed in the following work.

Handley's Thread Lymphangioplasty Vs. BioBridgetm Collagen Matrix for Lymphedema Therapy - Old Wine in New Bottles?

Lymphangioplasty is a technique of reconstructive lymphatic surgery where subcutaneous lymphatic neocollectors are created, using surgical threads, nanofibrillar collagen threads, plastic tubes or autologous tissue flaps. The history and success rates of these techniques are outlined and a classification for lymphangioplasty techniques is proposed. The use of absorbable surgical threads is suggested for modern attempts of thread lymphangioplasties. The results of such a thread lymphangioplasty should be compared with that of implanted nanofibrillar collagen threads or plastic tubes in order to evaluate whether the technique itself or the material used is responsible for the therapeutic success.

The Fate of Implanted BioBridgetm Collagen Matrix - Findings in Histology, Scanning, and Transmission Electron Microscopy.

The technique of lymphangioplasty or capillary thread drainage was historically performed with subcutaneously implanted surgical threads. It has recently been revived by introducing a thread-like aligned nanofibrillar collagen matrix (BioBridgetm). These collagen threads consitute subcutaneous neocollectors along which guided lymphangiogenesis is said to occur secondarily. We present for the first time a tissue examination of a 10-month implanted BioBridgetm sample with surrounding tissue from a human subject by histology, scanning and transmission electron microscopy.

[Future therapeutic strategies for olfactory disorders: electrical stimulation, stem cell therapy, and transplantation of olfactory epithelium-an overview]. / Zukunftsweisende Therapieansätze bei Riechstörungen: elektrische Stimulation, Stammzelltherapie und Transplantation von Riechepithel ­ eine Übersicht.

Olfactory disorders may be temporary or permanent and can have various causes. Currently, many COVID-19 patients report a reduced or complete loss of olfactory function. A wide range of treatment options have been investigated in the past, such as olfactory training, acupuncture, medical therapy, transcranial magnetic stimulation, or surgical excision of olfactory epithelium, e.g., in severe qualitative smell disorders. The development of a bioelectric nose, e.g., in connection with direct electrical stimulation or transplantation of olfactory epithelium or stem cells, represent treatment options of the future. The basis of these developments and the state of knowledge is discussed in the following work.

The shifting picture of HIV treatment, comorbidity and substance use among US MSM living with HIV.

OBJECTIVES: People living with HIV (PLWH) have increased risk of chronic disease and poor mental health. We aimed to explore HIV disease indicators, comorbidity, and risk behavior of recent antiretroviral therapy (ART) initiators to inform current needs of PLWH. METHODS: Men who have sex with men (MSM) in the Multicenter AIDS Cohort Study (MACS) who initiated ART between 2010 and 2018 (recent initiators) were compared with age-, race- and geographic location-matched men who initiated ART during 2000-2009 (early initiators). Measures of HIV disease, behavior, comorbidity and mental health were collected prospectively every 6 months using standardized forms. RESULTS: Recent initiators had higher current CD4 (median CD4 451 vs. 307 cells/µL, P < 0.0001) and nadir CD4 (451 vs. 300 cells/µL, P < 0.0001) than earlier initiators. The proportion achieving viral suppression within a year of starting ART was significantly higher in recent compared with earlier initiators (92% vs. 74%, P < 0.0001). Median [interquartile range (IQR)] time from HIV diagnosis to ART initiation was 5.4 (1.7-23.1) months in recent initiators. Comorbidity prevalence was high in recent initiators, including obesity (24%), hypertension (25%) and kidney disease (15%). Substance use continues to be common, including cigarette use (40%), daily alcohol use (88%) and marijuana use (46%). CONCLUSIONS: Improvements in getting individuals onto ART at an early stage have led to substantially higher CD4 cell counts at initiation. However, the high burden of comorbidity, substance use and poor mental health affecting MSM living with HIV in the US underscore ongoing challenges and our need to adapt and coordinate care.

Intracranial metastasis from a malignant peripheral nerve sheath tumor in a patient with neurofibromatosis type 1: A case study and literature review.

INTRODUCTION: Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are a rare type of soft tissue sarcoma. While these tumors often metastasize, intracranial metastases of MPNSTs have only been rarely noted. METHODS: Using Pubmed, Google Scholar, and Science Direct we conducted a systematic review of the literature to identify all reported cases of MPNSTs with metastases to the brain since the inception of these databases through January 2020. Data were extracted and data analysis was completed using python statistical packages. RESULTS: Only 26 cases (including present study) of MPNSTs resulting in intracranial metastases have been reported in the literature. Eight of these 26 cases occurred in patients who were previously diagnosed with Neurofibromatosis Type 1 (NF1). Additionally, one patient had been previously diagnosed with Neurofibromatosis Type 2 (NF2). The average reported time from diagnosis of a MPNST to the time of diagnosis with intracranial metastasis was 36 months, with a median time of 14 months. The average reported survival time for patients after being diagnosed with intracranial metastasis was 5.9 months. The cases that utilized a combination of therapeutic intervention including surgical resection, radiotherapy and chemotherapy saw the greatest improvement of survival times. CONCLUSION: MPNSTs with brain metastases are extremely rare and have a poor prognosis with a 6 months median survival after metastasis. While combination therapy is indicated, further studies on treatment are needed to determine survival benefits. Early and effective initial diagnosis of MPNST before brain metastases occurs is likely to give the best chance of increased overall survival.

25 Hydroxy Vitamin D Level, Bone Health, Vitamin D and Calcium Intake in Chilean Patients with Phenylketonuria and Hyperphenylalaninemias

Abstract It has been shown that there is a decrease in the concentrations of 25 hydroxyvitamin D (25-OHD) and bone mineral density (BMD) in patients with phenylketonuria (PKU) in their follow-up. Our objective was to determine concentrations of 25-OHD in subjects with PKU and hyperphenylalaninemia (HPA). Transversal analytical study considered three groups: G1-PKU with neonatal diagnosis and formula intake without Phe; G2-HPA, without specific treatment and G3-C control group. Sixteen patients per group (aged 6-23) were included. Levels of 25-OHD, lumbar spine (L2-L4), femur and total BMD, intact parathormone (PTH) and vitamin D (VitD) and calcium intake were calculated. The Kruskal-Wallis statistical test was applied (p-value<0,05). Significant differences were detected in concentrations of 25-OHD between G1-PKU and G2-HPA (38.9 ng/mL; 28 ng/mL, respectively) (NV: >30 ng/mL). G1-PKU had a higher intake of VitD, with differences among groups. There were no significant differences among groups in relation to BMD and intact PTH. In conclusion, G1-PKU under treatment and with good adherence, does not present VitD deficiency and no BMD alterations are observed. In contrast, G2-HPA had a lower intake of VitD and decreased 25-OHD concentrations which could affect the bone architecture in the long term. Further studies on the G2-HPA are suggested.

Quantitative Determination of Branched-Chain Amino Acids in Dried Blood Spot Samples by LC-MSMS and its Application in Diagnosis and Follow-Up of Chilean Patients with Maple Syrup Urine Disease

Abstract Elevation of branched-chain amino acids (BCAAs) in biological fluids indicates a deficiency in the branched-chain ketoacid dehydrogenase complex, which causes maple syrup urine disease (MSUD). Detection of increased levels of alloisoleucine confirms the diagnosis, while routine monitoring of leucine concentration is crucial for preventing metabolic decompensation and neurological dysfunction. In the metabolic center at Universidad de Chile, we have confirmed and monitored more than fifty MSUD patients in the last 20 years. Most diagnoses were made by clinical and sibling diagnosis, as MSUD is not included in the Chilean national newborn screening program. Shortening diagnosis time has a fundamental impact on the outcome of patients, therefore we focused on implementing detection of BCAAs in dried blood spot by liquid chromatography mass spectrometry (LC-MSMS) for disease confirmation as well as for biochemical monitoring. Retrospective analysis of samples from 9 diagnosed MSUD patients were performed; BCAAs values were determined via MSMS and LC-MSMS conducted in parallel. Leucine and alloisoleucine levels were positively correlated with patient's diagnosis age. Alloisoleucine was significatively elevated as early as 24 hr after birth. A predictable variation in BCAAs levels after nutritional intervention among diagnosed MSUD patients was found.

Update on Dietary Compliance, Nutritional Status, and Neuropsychological Functioning in the Chilean Phenylketonuria cohort

Abstract Since 1992, Chile has had a Newborn Screening Program for Phenylketonuria (PKU), which currently has an incidence of 1:18,916 newborns. The objective of the current study was to describe the 2020 follow up of the Chilean PKU cohort. The variables analyzed were: nutritional status, dietary compliance and neuropsychological functioning. We conducted a descriptive cross-sectional statistical analysis. The 271 subjects with PKU had an average age of diagnosis of 17±8 days and a phenylalanine (Phe) level of 1122±546 umol/L. Approximately 80% of protein requirement came from a protein substitute. For those <18 years of age, 80% had good dietary compliance with Phe level between 120-360 umol/L and those >18 years had a median of 522 umol/L (95%CI 468 - 636). Forty-four percent of the active PKU cohort had overweight/obesity. Eighty-five percent of the cohort >4 years of age had a normal intelligence quotient (IQ) (score 80-120). We observed a negative correlation (p <0.001; 95% CI: - 0.5, -0.2) between IQ score and Phe level. The Chilean protocol and protein substitute subsidy for life, together with the follow-up and continuous education carried out by the clinical team has encouraged compliance.

Validation of a pseudo-3D phantom for radiobiological treatment plan verifications.

Performing realistic and reliable in vitro biological dose verification with good resolution for a complex treatment plan remains a challenge in particle beam therapy. Here, a new 3D bio-phantom consisting of 96-well plates containing cells embedded into Matrigel matrix was investigated as an alternative tool for biological dose verification. Feasibility tests include cell growth in the Matrigel as well as film dosimetric experiments that rule out the appearance of field inhomogeneities due to the presence of the well plate irregular structure. The response of CHO-K1 cells in Matrigel to radiation was studied by obtaining survival curves following x-ray and monoenergetic 12C ion irradiation, which showed increased radioresistance of 3D cell cultures in Matrigel as compared to a monolayer. Finally, as a proof of concept, a 12C treatment plan was optimized using in-house treatment planning system TRiP98 for uniform cell survival in a rectangular volume and employed to irradiate the 3D phantom. Cell survival distribution in the Matrigel-based phantom was analyzed and compared to cell survival in a reference setup using cell monolayers. Results of both methods were in good agreement and followed the TRiP98 calculation. Therefore, we conclude that this 3D bio-phantom can be a suitable, accurate alternative tool for verifying the biological effect calculated by treatment planning systems, which could be applied to test novel treatment planning approaches involving multiple fields, multiple ion modalities, complex geometries, or unconventional optimization strategies.

Subclinical cardiovascular disease in HIV controller and long-term nonprogressor populations.

OBJECTIVES: Elite controllers (ECs), viraemic controllers (VCs), and long-term nonprogressors (LTNPs) control HIV viral replication or maintain CD4 T-cell counts without antiretroviral therapy, but may have increased cardiovascular disease (CVD) risk compared to HIV-uninfected persons. We evaluated subclinical carotid and coronary atherosclerosis and inflammatory biomarker levels among HIV controllers, LTNPs and noncontrollers and HIV-uninfected individuals in the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV Study (WIHS). METHODS: We measured carotid plaque presence and common carotid artery intima-media thickness (IMT) in 1729 women and 1308 men, and the presence of coronary artery calcium and plaque in a subgroup of men. Associations between HIV control category and carotid and coronary plaque prevalences were assessed by multivariable regression analyses adjusting for demographics and CVD risk factors. Serum inflammatory biomarker concentrations [soluble CD163 (sCD163), soluble CD14 (sCD14), galectin-3 (Gal-3), galectin-3 binding protein (Gal-3BP) and interleukin (IL)-6] were measured and associations with HIV control category assessed. RESULTS: We included 135 HIV controllers (30 ECs) and 135 LTNPs in the study. Carotid plaque prevalence and carotid IMT were similar in HIV controllers, LTNPs and HIV-uninfected individuals. HIV controllers and LTNPs had lower prevalences of carotid plaque compared to viraemic HIV-infected individuals. The prevalence of coronary atherosclerosis was similar in HIV controllers/LTNPs compared to HIV-uninfected and viraemic HIV-infected men. Controllers and LTNPs had higher concentrations of sCD163 and sCD14 compared to HIV-uninfected persons. CONCLUSIONS: Subclinical CVD was similar in HIV controllers, LTNPs and HIV-uninfected individuals despite elevated levels of some inflammatory biomarkers. Future studies of HIV controllers and LTNPs are needed to characterize the risk of CVD among HIV-infected persons.

Transcriptomic population markers for human population discrimination.

BACKGROUND: Numerous studies have demonstrated significant differences in the expression level across continental human populations. Most of published results were performed on B-cell lines materials examined under specific laboratory conditions, without further validation in a primary biological material. The goal of our study was to identify mRNA markers characterized by a significant and stable difference in the gene expression profile in Caucasian and Chinese populations, both in the commercially available B-lymphocyte cell lines and in the primary samples of the peripheral blood. RESULTS: The preliminary selection of population-differentiating transcripts was based on Illumina expression microarray analysis of the representative group of ethnically-specified B-lymphocyte cell lines. Twenty genes with the inter-population difference in the mean expression characterized by the at least 1.5-fold change and FDR <  0.05 were identified. Subsequently, a two-step validation procedure was carried out. In the first step, a subset of selected population- differentiating transcripts was tested in the independent set of B-lymphocyte cell lines, using TLDA cards. Based on TLDA analysis, three transcripts representing Fch > 2 were chosen for validation. The differentiating status was confirmed for all of them: UTS2, UGT2B17 and SLC7A7. The mean expression of UTS2 was higher in CHB (25.8-fold change compared to CEU), while the expression of UGT2B17 and SLC7A7 was higher in CEU (3.2- and 2.2-fold change, respectively). In the next validation step, two transcripts were verified in the primary biological material. As an ultimate result of our study, two mRNA markers (UTS2 and UGT2B17) exhibiting population differences in the expression level in both B-cell line and in the blood were identified. Further statistical analysis confirmed the discriminatory potential of these two markers. CONCLUSIONS: An inter-population differences on the level of gene expression were identified in both B-cell lines and peripheral blood samples. These findings may have a practical application in the field of forensic science. In particular, these transcripts, targeted by specific probes, may be used as population-specific targets in the efforts aiming to separate mixture of blood from individuals of different populations. Notwithstanding, these results have to be confirmed on extended population group.

Untargeted metabolomics identifies a plasma sphingolipid-related signature associated with lifestyle intervention in prepubertal children with obesity.

OBJECTIVE: Childhood obesity is a strong risk factor for adult obesity and metabolic diseases, including type 2 diabetes and cardiovascular disease. Early lifestyle intervention in children with obesity reduces future disease risk. The objective of this study is to identify metabolic signatures associated with lifestyle intervention in prepubertal children with obesity. METHODS: Thirty-five prepubertal children (7-10 years) with obesity (body mass index (BMI)>2 standard deviations) were enrolled in the study and participated in a 6-month-long lifestyle intervention program. Physiological and biochemical data and blood samples were collected both at baseline and after the intervention. A liquid chromatography-mass spectrometry (LC-MS)-based metabolomics approach was applied to obtain a comprehensive profiling of plasma samples, identifying 2581 distinct metabolite. Principal component analysis (PCA) was performed to consolidate all features into 8 principal components. Associations between metabolites and physiological and biochemical variables were investigated. RESULTS: The intervention program significantly decreased mean (95% CI) BMI standard deviation score from 3.56 (3.29-3.84) to 3.11 (2.88-3.34) (P<0.001). PCA identified one component (PC1) significantly altered by the intervention (Bonferroni adjusted P=0.008). A sphingolipid metabolism-related signature was identified as the major contributor to PC1. Sphingolipid metabolites were decreased by the intervention, and included multiple sphingomyelin, ceramide, glycosylsphingosine and sulfatide species. Changes in several sphingolipid metabolites were associated with intervention-induced improvements in HbA1c levels. CONCLUSIONS: Decreased circulating sphingolipid-related metabolites were associated with lifestyle intervention in prepubertal children with obesity, and correlated to improvements in HbA1c.

[Efficacy and safety analysis of off-label treatment with biologics in autoinflammatory diseases : Experiences from a German registry (GRAID2)]. / Wirksamkeits- und Sicherheitsanalyse von Off-label-Biologikatherapien bei Patienten mit autoinflammatorischen Erkrankungen : Erfahrungen aus einem Deutschen Register (GRAID2).

OBJECTIVE: To evaluate the safety and efficacy of therapy with biologics in patients with autoinflammatory diseases (AIF) or macrophage activating syndrome (MAS) in a real-life setting in Germany. METHODS: The German Register of Autoimmune Diseases 2 (GRAID2) is a retrospective, non-interventional, multicenter registry collecting data from all patients with inflammatory rheumatic diseases refractory to conventional therapy and treated with initial off-label biologics between August 2006 and December 2013. Patients with MAS could be included without prior treatment with a biologic agent. RESULTS: Data from 26 patients with AIF and 5 with MAS were collected. Of the AIF patients 13 (50%) were diagnosed with adult onset Still's disease (AOSD), 6 (23%) with familial Mediterranean fever (FMF), 4 (15.4%) with tumor necrosis factor-associated periodic syndrome (TRAPS), 1 (3.8%) patient with cryopyrin-associated periodic syndrome (CAPS) and 2 (8%) with undifferentiated fever syndromes. The 5 MAS patients suffered from rheumatoid arthritis (RA) with chronic myeloid leukemia, systemic lupus erythematosus and in 2 cases AOSD. In 1 patient a chronic neurological disease was documented without further differentiaton. All patients with TRAPS were primarily treated with etanercept and all CAPS patients with canakinumab. The AOSD and FMF patients were treated with anakinra as the first line off-label biologic in 6 out of 13 and 5 out of 6 cases, respectively. The MAS patients responded very well or well to therapy in 40% and 60% had a moderate response. There were no non-responders. Within the group of AIF patients the physicians documented a very effective or effective treatment in 38.5%, a moderate response in 30.8% and no response in 30.7%. The tolerance was very good in 5 out of 5 of the MAS and in 92% of the AIF patients. CONCLUSION: The data of this retrospective register provide indications for an effective and safe treatment with off-label biologic medication in patients with AIF and MAS in daily practice.

[Off-label biological therapies in patients with large vessel vasculitis and/or polymyalgia rheumatica : Safety and efficacy analysis of a nationwide German registry (GRAID2)]. / Off-label-Biologikatherapie bei Patienten mit Großgefäßvaskulitiden und/oder Polymyalgia rheumatica : Wirksamkeits- und Sicherheitsanalyse eines nationalen Registers (GRAID2).

OBJECTIVE: To evaluate the safety and clinical outcome of biological therapies in patients with large vessel vasculitis (LVV) or polymyalgia rheumatica (PMR) refractory to standard of care therapy in a real-life setting in Germany. METHODS: GRAID 2 (German Registry in Autoimmune Diseases 2) is a retrospective, noninterventional, multicenter registry collecting data from all patients with inflammatory rheumatic diseases refractory to conventional therapy treated with an initial off-label biological between August 2006 and December 2013. The retrospective documentation comprised case history, diagnosis, course of disease including safety and overall efficacy. RESULTS: Data from 14 patients were collected, 11 with LVV (78.6%) and 3 with isolated PMR (21.4%). Ten patients were treated with tocilizumab (71.4%), while 3 patients received infliximab infusions (21.4%) and 1 patient was treated with rituximab (7.1%). All clinical as well as laboratory efficacy parameters improved substantially. After the first application, tolerability of biologicals was assessed as "very good"/"good" by the physicians in 92.3% of the patients. Altogether, 8 adverse events (AEs) occurred in 4 patients including 3 infections (1 urogenital infection, 2 diverticulitis) representing a rate of 23.6 infections per 100 patient-years. One of these infections (diverticulitis under infliximab treatment) was rated as serious AE, requiring ICU treatment representing a rate of serious AEs of 7.9 per 100 patient-years. No deaths occurred during the observation period. CONCLUSION: With known limitations of a retrospective database, the results of this survey confirm data of smaller case series and proof-of-concept studies and suggest a substantial response to biological therapies in patients with otherwise refractory LVV or PMR with no new safety signals.

Pupillary autonomic dysfunction in patients with ANCA-associated vasculitis.

OBJECTIVE: To assess autonomic function by infrared dynamic pupillometry in patients with ANCA-vasculitis (AAV) in correlation to autonomic symptoms, disease specific clinical parameters and cardiovascular reflex tests. METHODS: Patients with AAV and healthy controls underwent pupillometry at rest and after sympathetic stimulation (cold pressor test). Three parasympathetic parameters (amplitude, relative amplitude, maximum constriction velocity) and one sympathetic parameter (late dilatation velocity) were assessed. Results were correlated with clinical parameters, symptoms of autonomic dysfunction (COMPASS31 questionnaire), heart rate variability during deep breathing test and blood pressure response to pain. RESULTS: 23 patients and 18 age-matched controls were enrolled. Patients had a smaller amplitude (1.44 vs. 1.70 mm; p = 0.009) and a slower constriction velocity (4.15 vs. 4.71 mm/s; p = 0.028) at baseline and after sympathetic stimulation (1.47 vs. 1.81 mm, p = 0.001; 4.38 vs. 5.19 mm/s, p = 0.006, respectively). Relative amplitude was significantly smaller in patients after sympathetic stimulation (28.6 vs. 32.5%; p = 0.043), but not at baseline. There was no difference in sympathetic pupillary response between the groups. In patients, parasympathetic pupil response was correlated negatively with age and positively with parasympathetic cardiac response. After adjusting for age, no significant correlation was observed with clinical parameters. However, there was a trend towards a negative correlation with disease duration, vasculitis damage index and CRP. CONCLUSION: Patients with AAV exhibit parasympathetic pupillary autonomic dysfunction. Although correlations were weak and not significant, pupillary autonomic dysfunction is rather linked to chronic damage than to active inflammation or symptoms of autonomic dysfunction.

Long-term satellite tracking reveals variable seasonal migration strategies of basking sharks in the north-east Atlantic.

Animal migration is ubiquitous in nature with individuals within a population often exhibiting varying movement strategies. The basking shark (Cetorhinus maximus) is the world's second largest fish species, however, a comprehensive understanding of their long-term wider-ranging movements in the north-east Atlantic is currently lacking. Seventy satellite tags were deployed on basking sharks over four years (2012-2015) off the west coast of Scotland and the Isle of Man. Data from 28 satellite tags with attachment durations of over 165 days reveal post-summer ranging behaviours. Tagged sharks moved a median minimum straight-line distance of 3,633 km; achieving median displacement of 1,057 km from tagging locations. Tagged individuals exhibited one of three migration behaviours: remaining in waters of UK, Ireland and the Faroe Islands; migrating south to the Bay of Biscay or moving further south to waters off the Iberian Peninsula, and North Africa. Sharks used both continental shelf areas and oceanic habitats, primarily in the upper 50-200 m of the water column, spanning nine geo-political zones and the High Seas, demonstrating the need for multi-national cooperation in the management of this species across its range.