Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Elevated Epidermal Growth Factor (EGF) as Candidate Biomarker of Mood Disorders—Longitudinal Study in Adolescent and Young Adult Patients

Bipolar disorder (BD) is a chronic mental disorder that affects more than 1% of the population worldwide. Over 65% of patients experience early onset of the disease. Most cases of juvenile bipolar disorder begin with a depressed mood episode, and up to 50% of youth initially diagnosed with major depression go onto developing a BD. Our study aimed to find biomarkers of diagnosis conversion in young patients with mood disorders. We performed a two-year follow-up study on 79 adolescent patients diagnosed with MDD or BD, with a detailed clinical assessment at five visits. We monitored diagnosis change from MDD to BD. The control group consisted of 31 healthy youths. According to the neurodevelopmental and neuroimmunological hypotheses of mood disorders, we analyzed serum levels of brain-derived neurotrophic factor (BDNF), proBDNF, epidermal growth factor (EGF), migration inhibitory factor (MIF), stem cell factor (SCF), and correlations with clinical factors. We detected a significant disease-dependent increase in EGF level in MDD and BP patients at baseline exacerbation of depressive or hypomanic/manic episodes as well as in euthymic state compared to healthy controls. No potential biological predictors of disease conversion were found. Replication studies on a larger cohort of patients are needed

Parliamentary Committees and Their Role in Modern Society

Samkvæmt umboðskenningum framselja umbjóðendur valdi sínu til fulltrúa sem eiga að vinna og taka ákvarðanir með hagsmuni umbjóðenda að leiðarljósi. Þetta samband milli umbjóðenda og fulltrúa býður upp á umboðsvanda þar sem fulltrúi gætir frekar eigin hagsmuna eða hagsmuna ákveðinna hópa frekar en umbjóðandans. Í þingnefndakerfinu er umboðsvandi alltaf til staðar þar sem vinnan sem fer fram í nefndum er á bak við luktar dyr, það er því hlutverk þingsins að hafa eftirlit með nefndum og takast á við umboðsvandann. Íslenska þingnefndakerfið er frábrugðið þeim kerfum sem tíðkast á hinum Norðurlöndunum og þegar valdheimildir íslenskra nefnda eru bornar saman við valdheimildir nefnda á hinum Norðurlöndunum kemur áhugaverður munur í ljós. Það er einnig áhugavert að skoða hvernig valdsvið nefnda hefur stækkað í kjölfar efnahagshrunsins árið 2008 og breytinguna á andrúmsloftinu á Alþingi. Á árunum fyrir hrunið var meðaltal nefndafrumvarpa 7,88 á ári en árið 2016 fór meðaltalið upp í 18 frumvörp á ári. Þegar íslenska nefndakerfið er skoðað og skipting nefnda á árum 1959-2015 kemur meðal annars í ljós að þingmenn frá landsbyggðar-kjördæmum hafa mun sterkari stöðu í þingnefndum. Þrjár mjög áhrifamiklar þingnefndir, fjárlaganefnd, landbúnaðar- og sjávarútvegsnefnd og samgöngunefnd, voru skoðaðar og skipting landsbyggðarþingmanna og þingmanna sem komu úr kjördæmunum á höfuðborgarsvæðinu. Í ljósi þessara upplýsinga er tekið dæmi um eitt af umdeildustu málefnunum í íslensku samfélagi, kvótakerfið, og hvernig vald þingnefnda getur tryggt að breytingar verða ekki gerðar á núverandi kerfi. Helsta niðurstaða þessarar ritgerðar er að núverandi kjördæmakerfi tryggir mun sterkari stöðu landsbyggðarinnar á Alþingi og í þingnefndum. Kerfið tryggir þannig að ákveðinn hópur í samfélaginu hefur aukin völd til að viðhalda þeim valdastrúktúr sem ríkir á milli landsbyggðarkjördæma og kjördæma á höfuðborgarsvæðinu. Önnur niðurstaða var sú að völd þingnefnda hafa aukist í kjölfar hrunsins en eftirlit með þeim hefur ekki aukist samhliða því. Því hefur þingið fært enn meiri völd í hendur þingnefnda, sem eins og niðurstöður þessarar ritgerðar benda til hallar að ákveðnum hópum samfélagsins og ýtir því enn meira undir umboðsvanda þingsins

Experts on their local environment: Comparison of the implementation of citizen dialogue projects in Akureyri and in Kópavogur.

Viðfangsefni þessarar rannsóknar er tilraunaverkefni um íbúasamráð sem Samband íslenskra sveitarfélaga setti á laggirnar. Rannsóknin tekur fyrir innleiðingaferli verkefnisins í tveimur þátttökusveitarfélögum, Akureyri og Kópavogi, en samtals tóku fjögur sveitarfélög þátt í verkefninu. Markmið rannsóknarinnar var að greina innleiðingarferlið og lýsa því, rannsaka hvaða þættir höfðu áhrif á það og skoða hvaða lærdóm megi draga af þessu verkefni og yfirfæra á önnur sveitarfélög. Rannsókn þessi flokkast sem tilviksrannsókn og notast var við eigindlega rannsóknaraðferð. Tekin voru fimm viðtöl, þrjú við starfsmenn sem voru í stýrihópum verkefna þátttökusveitarfélaganna og tvö við ráðgjafa Alta sem veittu þátttökusveitarfélögunum ráðgjöf og aðstoð á meðan á ferlinu stóð. Gagnaöflun fór einnig fram á vinnustofum verkefnisins en höfundur sat þær vinnustofur. Bæði sveitarfélögin sem rannsóknin tók fyrir náðu að klára samráðsviðburði en eru enn þá að vinna í því að veita endurgjöf til þátttakenda. Þrátt fyrir að verkefnið sé í raun og veru búið þá hyggjast bæði sveitarfélög veita þessa endurgjöf á næstunni. Á heildina litið gekk innleiðing verkefnisins vel hjá báðum sveitarfélögum þó þau hafi mætt ólíkum áskorunum og hindrunum. Fleiri hindranir komu upp hjá Akureyri og er helsta skýring þess að einn af starfsmönnum vinnuhópsins í Kópavogi hafði mikla reynslu og sérþekkingu á sviði íbúasamráðs og náði því að fyrirbyggja helstu hindranir fyrir fram. Rannsóknin leiddi í ljós að staðbundnir þættir höfðu áhrif á verkefnið, stærri sveitarfélög höfðu ákveðið forskot sem birtist fyrst og fremst í þeim björgum sem settar voru í verkefnið. Forskot stærri sveitarfélaga kemur einnig fram í sérþekkingu starfsmanna sveitarfélaga en í stærri sveitarfélögum er líklegra að starfsmenn hafi sérþekkingu á ólíkum sviðum sem geta hjálpað við undirbúning og framkvæmd verkefna. Rannsóknin leiddi einnig í ljós að sveitarfélög skortir þekkingu og fræðslu á sviði íbúasamráðs, þær leiðbeiningar sem sveitarfélögin hafa aðgang að veitti þeim góða innsýn inn í íbúasamráð en til að gera íbúasamráð að hluta af ákvörðunartökum á sveitarstjórnarstiginu er þörf á meira fræðsluefni og stuðningi.The objective of this research is a citizen dialogue project that the Icelandic Association of Local Authorities put together. Four municipalities took part in the project; however, the research focuses on the implementation process of two of the participating municipalities, Akureyri and Kópavogur. The aim of the research was to analyse and describe the implementation process, investigate which factors affected it and what lessons can be learned from this project. Also, what other Icelandic municipalities can learn from this project. The research is classified as a case study and a qualitative research method was applied. Five interviews were conducted, three with employees of the participating municipalities and two with advisors from Alta, who provided assistance to participating municipalities during the project. Data collection also took place at the project’s workshops that the author attended. Both participating municipalities involved in the research had completed consultation events but are still working on providing participants feedback. Although the project is officially completed both municipalities intend to provide participants feedback soon. Overall the implementation process of the citizen dialogue project was a success although both municipalities faced different challenges and obstacles. Overall Akureyri encountered more obstacles than Kópavogur. One of the employees that took part in this project in Kópavogur had extensive experience and expertise in citizen participation and managed to prevent the major obstacles in advance. The research found that local factors, such as the size of municipalities and the experience of the employees, had an impact on the implementation process of the project therefore larger municipalities had certain advantage. Larger municipalities are more likely to have employees with expertise in diverse areas that can assist in the preparation and execution of this type of project. The study also revealed that municipalities lack knowledge and experience in citizen participation and citizen dialogue. Instructions that the municipalities have access to, provide them a good insight into citizen participation, however in order to make citizen participation part of the decision-making process at the municipal level, more educational material and support is needed

Peripheral S100B Protein Levels in Five Major Psychiatric Disorders: A Systematic Review

Five major psychiatric disorders: schizophrenia, major depressive disorder, bipolar disorder, autistic spectrum disorder, and attention-deficit/hyperactivity disorder, show a shared genetic background and probably share common pathobiological mechanisms. S100B is a calcium-binding protein widely studied in psychiatric disorders as a potential biomarker. Our systematic review aimed to compare studies on peripheral S100B levels in five major psychiatric disorders with shared genetic backgrounds to reveal whether S100B alterations are disease-specific. EMBASE, Web of Science, and PubMed databases were searched for relevant studies published until the end of July 2023. This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols (PRISMA) guidelines. Overall, 1215 publications were identified, of which 111 full-text articles were included in the systematic review. Study designs are very heterogeneous, performed mostly on small groups of participants at different stages of the disease (first-episode or chronic, drug-free or medicated, in the exacerbation of symptoms or in remission), and various clinical variables are analyzed. Published results are inconsistent; most reported elevated S100B levels across disorders included in the review. Alterations in S100B peripheral levels do not seem to be disease-specific

ProBDNF as an Indicator of Improvement among Women with Depressive Episodes

Depression is a chronic psychiatric disorder with a heavy socioeconomic burden. Studies on biomarkers are needed to comprehend the pathophysiology of depression and to improve treatment outcomes. Research points to the importance of imbalance between mature brain-derived neurotrophic factor (BDNF) and its precursor, pro–brain–derived neurotrophic factor (proBDNF), in the pathophysiology of mood disorders and the potential neurodegenerative role of calcium-binding protein B (S100B). Our objective was to compare BDNF, proBDNF, and S100B serum levels before and after the treatment of acute depressive episodes and to assess their correlation with the severity of symptoms and history of stress. We also aimed to investigate the differences in BDNF, proBDNF, and S100B levels between depression in the course of bipolar disorder (BD) and major depressive disorder (MDD). We recruited 31 female patients diagnosed with BD or MDD who were hospitalized due to current depressive episodes. The patients had their serum BDNF, proBDNF, and S100B levels evaluated using the ELISA method upon admission and after the symptoms improved, at discharge. We found that proBDNF levels decreased significantly with the treatment (p = 0.0478), while BDNF and S100B levels were not altered significantly. No differences in biochemical parameters between MDD and BD subjects were observed. Consequently, we concluded that a decrease in serum proBDNF levels could be considered a biomarker of recovery from depressive episodes

High-Density Lipoprotein Correlates with Cognitive Functioning in Schizophrenic Women

(1) Background: Schizophrenia is a chronic and progressive neuropsychiatric illness. Apart from positive and negative symptoms, 98% of the population diagnosed with schizophrenia have impaired cognitive functioning, which significantly influences the quality of life. The correlation between lipids and cognitive functioning has been well established. Our study aimed to investigate correlations between cognitive functions, the severity of schizophrenia symptoms, and lipid profiles. (2) Methods: Fifty-two women diagnosed with schizophrenia participated in this study. Cognitive functioning was measured using the Wisconsin Card Sorting Test (WCST). The Positive and Negative Symptom Scale (PANSS) was used. The serum lipid profile, including low-density lipoproteins (LDLs), high-density lipoproteins (HDLs), and triglycerides was measured. (3) Results: Better cognitive functions were associated with normal HDL levels, while low HDL levels correlated with worse WSCT scores. Only the PANSS negative subscale showed a correlation with HDL levels. Correlations with chronicity of schizophrenia and the patient’s age with poorer cognitive functions, but not with symptom severity, were detected. Early/late age at onset did not influence WSCT scores. (4) Conclusions: Our results suggest high HDL levels might be a protective factor against cognitive impairment. The influences of age and illness duration also play a vital role in cognitive performance