The International Protection of Women in Armed Conflicts

The protection of women during armed conflicts has from time to time been a matter of concern to the international community in various forms and degrees. The laws of war have regulated the protection of women long before the Geneva Conventions and additional protocols system. The aim of this paper is to highlight the protection that women should be given in armed conflict, also taking into account their special needs

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

Development and pilot implementation of a novel protocol to assess capacity and readiness of health systems to adopt HPV detection-based cervical cancer screening in Europe

BACKGROUND: Cervical cancer remains a significant public health concern in Europe. Effective introduction and scaling up of human papillomavirus (HPV) detection-based cervical cancer screening (CCS) requires a systematic assessment of health systems capacity. However, there is no validated capacity assessment methodology for CCS programmes, especially in European contexts. Addressing this gap, our study introduces an innovative and adaptable protocol for evaluating the capacity of CCS programmes across varying European health system settings. METHODS: Our research team developed a three-step capacity assessment framework, incorporating a health policy review checklist, a facility visit survey, and key informants' interview guide followed by a strengths, weaknesses, opportunities and threats (SWOT) analysis. Piloting this comprehensive approach, we explored the CCS capacity in three countries: Estonia, Portugal and Romania. These countries were selected due to their contrasting healthcare structures and resources, providing a diverse overview of the European context. RESULTS: Conducted over a period of 9 months, the capacity assessment covered multiple resources, 27 screening centres, 16 colposcopy and treatment centres and 15 key informant interviews. Our analysis highlighted both shared and country-specific challenges. A key common issue was ensuring high compliance to follow-up and management of screen-positive women. We identified considerable heterogeneity in resources and organization across the three countries, underscoring the need for tailored, rather than one-size-fits-all, solutions. CONCLUSIONS: Our study's novelty lies in the successful development of this capacity assessment methodology implementable within a relatively short time frame, proving its feasibility for use in various contexts and countries. The resulting set of materials, adaptable to different cancer types, is a ready-to-use toolkit to improve cancer screening processes and outcomes. This research marks a significant stride towards comprehensive capacity assessment for CCS programmes in Europe. Future directions include deploying these tools in other countries and cancer types, thereby contributing to the global fight against cancer. © 2024. The Author(s).CBIG-SCREEN has received funding from the EU Horizon 2020 Research and Innovation Programme under grant agreement no. 964049. Official starting date: 1 March 2021

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

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

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

Clinical Profile of Cardiac Involvement in Danon Disease: A Multicenter European Registry

Background: The X-linked Danon disease manifests by severe cardiomyopathy, myopathy, and neuropsychiatric problems. We designed this registry to generate a comprehensive picture of clinical presentations and outcome of patients with Danon disease in cardiomyopathy centers throughout Europe. Methods: Clinical and genetic data were collected in 16 cardiology centers from 8 European countries. Results: The cohort comprised 30 male and 27 female patients. The age at diagnosis was birth to 42 years in men and 2 to 65 in women. Cardiac involvement was observed in 96%. Extracardiac manifestations were prominent in men but not in women. Left ventricular (LV) hypertrophy was reported in 73% of male and 74% of female patients. LV systolic dysfunction was reported in 40% of men (who had LV ejection fraction, 34±11%) and 59% of women (LV ejection fraction, 28±13%). The risk of arrhythmia and heart failure was comparable among sexes. The age of first heart failure hospitalization was lower in men (18±6 versus 28±17 years; P<0.003). Heart failure was the leading cause of death (10 of 17; 59%), and LV systolic dysfunction predicted an adverse outcome. Eight men and 8 women (28%) underwent heart transplantation or received an LV assist device. Our cohort suggests better prognosis of female compared with male heart transplant recipients. Conclusions: Danon disease presents earlier in men than in women and runs a malignant course in both sexes, due to cardiac complications. Cardiomyopathy features, heart failure and arrhythmia, are similar among the sexes. Clinical diagnosis and management is extremely challenging in women due to phenotypic diversity and the absence of extracardiac manifestations

Atypical cardiac defects in patients with RASopathies: Updated data on CARNET study

Background: RASopathies are a set of relatively common autosomal dominant clinically and genetically heterogeneous disorders. Cardiac outcomes in terms of mortality and morbidity for common heart defects (such as pulmonary valve stenosis and hypertrophic cardiomyopathy) have been reported. Nevertheless, also Atypical Cardiac Defects (ACDs) are described. The aim of the present study was to report both prevalence and cardiac outcome of ACDs in patients with RASopathies. Methods: A retrospective, multicentric observational study (CArdiac Rasopathy NETwork—CARNET study) was carried out. Clinical, surgical, and genetic data of the patients who were followed until December 2019 were collected. Results: Forty‐five patients out of 440 followed in CARNET centers had ACDs. Noonan Syndrome (NS), NS Multiple Lentigines (NSML) and CardioFacioCutaneous Syndrome (CFCS) were present in 36, 5 and 4 patients, respectively. Median age at last follow‐up was 20.1 years (range 6.9–47 years). Different ACDs were reported, including mitral and aortic valve dysfunction, ascending and descending aortic arch anomalies, coronary arteries dilation, enlargement of left atrial appendage and isolated pulmonary branches diseases. Five patients (11%) underwent cardiac surgery and one of them underwent a second intervention for mitral valve replacement and severe pericardial effusion. No patients died in our cohort until December 2019. Conclusions: Patients with RASopathies present a distinct CHD spectrum. Present data suggest that also ACDs must be carefully investigated for their possible impact on the clinical outcome. A careful longitudinal follow up until the individuals reach an adult age is recommended

Genome-Wide Expression Analysis of a Spinal Muscular Atrophy Model: Towards Discovery of New Drug Targets

Spinal Muscular Atrophy is a recessive genetic disease and affects lower motor neurones and muscle tissue. A single gene is disrupted in SMA: SMN1 activity is abolished but a second copy of the gene (SMN2) provides limited activity. While the SMN protein has been shown to function in the assembly of RNA-protein complexes, it is unclear how the overall reduction in SMN activity specifically results in the neuromuscular phenotypes. Similar to humans, reduced smn activity in the fly causes earliest phenotypes in neuromuscular tissues. To uncover the effects of reduced SMN activity, we have studied gene expression in control and diseased fly tissues using whole genome micro-arrays. A number of gene expression changes are recovered and independently validated. Identified genes show trends in their predicted function: several are consistent with the function of SMN, in addition some uncover novel pathways. This and subsequent genetic analysis in the fly indicates some of the identified genes could be taken for further studies as potential drug targets for SMA and other neuromuscular disorders