Atrioventricular canal defect and genetic syndromes: the unifying role of sonic hedgehog

The atrioventricular canal defect (AVCD) is a congenital heart defect (CHD) frequently associated with extracardiac anomalies (75%). Previous observations from a personal series of patients with AVCD and "polydactyly syndromes" showed that the distinct morphology and combination of AVCD features in some of these syndromes is reminiscent of the cardiac phenotype found in heterotaxy, a malformation complex previously associated with functional cilia abnormalities and aberrant Hedgehog (Hh) signaling. Hh signaling coordinates multiple aspects of left-right lateralization and cardiovascular growth. Being active at the venous pole the secondary heart field (SHF) is essential for normal development of dorsal mesenchymal protrusion and AVCD formation and septation. Experimental data show that perturbations of different components of the Hh pathway can lead to developmental errors presenting with partially overlapping manifestations and AVCD as a common denominator. We review the potential role of Hh signaling in the pathogenesis of AVCD in different genetic disorders. AVCD can be viewed as part of a "developmental field," according to the concept that malformations can be due to defects in signal transduction cascades or pathways, as morphogenetic units which may be altered by Mendelian mutations, aneuploidies, and environmental causes

Milking Characteristics of Istrian and Littoral Dinaric Donkey Breeds

Istrian and Littoral Dinaric donkey are autochthonous breeds which habitat primarily in the Mediterranean part of Croatia. During the second half of the 20th century they have lost primary function as working animals, which led to breeds suppression. Nowadays these two breeds are in the status of endangered ones. One of the possibilities for their economic re-affirmation is launching the program for production and processing donkey’s milk. The aim of the study was to determine the possibility of milk production of Istrian and Littoral Dinaric jennies in terms of quantity and chemical composition. Istrian jennies produce 745.4 mL/milking while Littoral Dinaric produce 317.8 mL/milking. Milk form Littoral Dinaric jennies contained a significantly higher proportion of milk fat and proteins. There were no significant differences in the content of lactose, dry matter, number of somatic cells and microorganisms in milk between these two breeds. Considering the potential for milk production and milk quality, we believe that both breeds are suitable for integration in the programs for milk production, thus enabling for both population to be economically sustainable. It is necessary to develop production technology and markets, with special emphasis considering quality of donkey milk and safety of consumers

First evidence of maternally inherited mosaicism in TGFBR1 and subtle primary myocardial changes in Loeys-Dietz syndrome: a case report

Background: Loeys-Dietz syndrome (LDS) is a rare multisystemic disorder characterized by vascular and skeletal abnormalities, with considerable intra- and interfamilial variability. Case presentation: We report the case of an 8-year-old male with clinical features of two distinct genetic disorders, namely LDS, manifesting in the first months by progressive aortic root dilatation, arterial tortuosity, bifid uvula, and inguinal hernias and oculocutaneous albinism (OCA) manifesting by white hair and skin that does not tan, nystagmus, reduced iris pigment with iris translucency, and reduced retinal pigment). We identified previously reported, homozygous mutations of TYR, c.1A > G (p.Met1Val) and heterozygous, missense mutation of TGFBR1, c.1460G > A (p.Arg487Gln). Family history revealed that his mother underwent multiple surgical repairs for recurrent hemorrhage originating from the buccal artery. Molecular studies confirmed a maternally inherited low grade TGFBR1 mutation somatic mosaicism (18% in peripheral blood leukocytes, 18% in buccal cells and 10% in hair root cells). Maternal cardiac investigations revealed peculiar cardiovascular features: mild tortuosity at the aortic arch, dilatation of the proximal abdominal aorta, multiple deep left ventricular myocardial crypts, and dysplastic mitral valve. TGFBR2 germline mosaicism has been described in three fathers of children carrying TGFBR2 mutations but, to the best of our knowledge, no case of maternally inherited TGFBR1 mutation mosaicism has been reported so far. Conclusions: This case report suggests that individuals with somatic mosaicism might be at risk for mild and unusual forms of LDS but germline mosaicism can lead to full blown picture of the disease in offspring

Identification of adverse childhood experiences strongly predicting suicidal behaviour among emerging adults in Montenegro and Romania: A new way to targeted cost-effective prevention

Introduction. Aiming at generating evidence for cost-effective public health (PH) interventions for suicidal behaviour (SB) prevention in South Eastern Europe, the objective was to identify adverse childhood experiences (ACEs) most strongly predicting SB in emerging adults. Methods. Survey data of 3283 students aged 18-29 from Montenegro and Romania were analysed by logistic regression. Based on estimation of risk-for-SB, the profiles with the highest values were identified. Results. The SB odds were the highest in respondents, experienced a suicide attempt in the household (OR: 13.81; p < 0.001), and whose primary family was not complete, in particular in those with the foster family background (OR: 18.30; p = 0.001). Conclusions. Magnitude of impact on emerging adults' mental health vulnerability tends to vary considerably with individual ACEs. This should be considered carefully when developing cost-effective response to SB burden through PH interventions in particular at the times of financial crises and in scarce resources settings

Impact of adverse childhood experiences on alcohol use in emerging adults in Montenegro and Romania

Aiming at generating evidence for formulating targeted and cost-effective public health interventions for the effective control of alcohol use (AU) in emerging adults in South Eastern Europe. The study's objective was to assess if alcohol users experience adverse childhood experiences (ACE) more often than non-users, and to identify which ACE victims are the most vulnerable to AU. The data was collected in 2010-2012 in two cross-sectional studies conducted in university settings in Montenegro and Romania (overall response rate 89.1%). In the present study, 3,283 students were included. The international ACE Study Questionnaires were used as a base for study instruments for collecting information on ACEs, health behaviours, and socio-economic factors. The association between AU and individual ACEs, adjusted to background factors, was assessed by using logistic regression. From the child maltreatment group, three ACEs were included in the final model as statistically significantly associated with AU, all of them from physical neglect/abuse types: frequently being hit so hard to have marks or being injured (OR=1.68; p=0.012), frequently being spanked (OR=1.38; p=0.012), and frequently having no person to take to the doctor if necessary (OR=0.58; p=0.031). From the household dysfunction group, two ACEs were included in the final model: exposure to mental health problems in the household (OR=2.85; p<0.001), and living with a problematic drinker/alcoholic (OR=1.51; p=0.019). The effect of exposure to ACEs on AU persists into emerging adulthood. This should be considered when developing cost-effective response to AU burden through targeted interventions, in particular in settings with scarce resources

Synthesis of Fluorine-18 Functionalized Nanoparticles for use as in vivo Molecular Imaging Agents

Nanoparticles containing fluorine-18 were prepared from block copolymers made by ring opening metathesis polymerization (ROMP). Using the fast initiating ruthenium metathesis catalyst (H_2IMes)(pyr)_2(Cl)_2Ru=CHPh, low polydispersity amphiphilic block copolymers were prepared from a cinnamoyl-containing hydrophobic norbornene monomer and a mesyl-terminated PEG-containing hydrophilic norbornene monomer. Self-assembly into micelles and subsequent cross-linking of the micelle cores by light-activated dimerization of the cinnamoyl groups yielded stable nanoparticles. Incorporation of fluorine-18 was achieved by nucleophilic displacement of the mesylates by the radioactive fluoride ion with 31% incorporation of radioactivity. The resulting positron-emitting nanoparticles are to be used as in vivo molecular imaging agents for use in tumor imaging

Challenges in QCD matter physics --The scientific programme of the Compressed Baryonic Matter experiment at FAIR

Substantial experimental and theoretical efforts worldwide are devoted to explore the phase diagram of strongly interacting matter. At LHC and top RHIC energies, QCD matter is studied at very high temperatures and nearly vanishing net-baryon densities. There is evidence that a Quark-Gluon-Plasma (QGP) was created at experiments at RHIC and LHC. The transition from the QGP back to the hadron gas is found to be a smooth cross over. For larger net-baryon densities and lower temperatures, it is expected that the QCD phase diagram exhibits a rich structure, such as a first-order phase transition between hadronic and partonic matter which terminates in a critical point, or exotic phases like quarkyonic matter. The discovery of these landmarks would be a breakthrough in our understanding of the strong interaction and is therefore in the focus of various high-energy heavy-ion research programs. The Compressed Baryonic Matter (CBM) experiment at FAIR will play a unique role in the exploration of the QCD phase diagram in the region of high net-baryon densities, because it is designed to run at unprecedented interaction rates. High-rate operation is the key prerequisite for high-precision measurements of multi-differential observables and of rare diagnostic probes which are sensitive to the dense phase of the nuclear fireball. The goal of the CBM experiment at SIS100 (sNN= 2.7--4.9 GeV) is to discover fundamental properties of QCD matter: the phase structure at large baryon-chemical potentials (μB&gt; 500 MeV), effects of chiral symmetry, and the equation of state at high density as it is expected to occur in the core of neutron stars. In this article, we review the motivation for and the physics programme of CBM, including activities before the start of data taking in 2024, in the context of the worldwide efforts to explore high-density QCD matter

Prenatal attachment: using measurement invariance to test the validity of comparisons across eight culturally diverse countries

Studies in high-income countries (HICs) have shown that variability in maternal-fetal attachment (MFA) predict important maternal health and child outcomes. However, the validity of MFA ratings in low- and middle-income countries (LMICs) remains unknown. Addressing this gap, we assessed measurement invariance to test the conceptual equivalence of the Prenatal Attachment Inventory (PAI: Muller, 1993) across eight LMICs. Our aim was to determine whether the PAI yields similar information from pregnant women across different cultural contexts. We administered the 18-item PAI to 1181 mothers in the third trimester (Mean age = 28.27 years old, SD = 5.81 years, range = 18–48 years) expecting their first infant (n = 359) or a later-born infant (n = 820) as part of a prospective birth cohort study involving eight middle-income countries: Ghana, Jamaica, Pakistan, Philippines, Romania, South Africa, Sri Lanka and Vietnam. We used Multiple Group Confirmatory Factor Analyses to assess across-site measurement invariance. A single latent factor with partial measurement invariance was found across all sites except Pakistan. Group comparisons showed that mean levels of MFA were lowest for expectant mothers in Vietnam and highest for expectant mothers in Sri Lanka. MFA was higher in first-time mothers than in mothers expecting a later-born child. The PAI yields similar information about MFA across culturally distinct middle-income countries. These findings strengthen confidence in the use of the tool across different settings; future studies should explore the use of the PAI as a screen for maternal behaviour that place children at risk