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Introduction:Diencephalic-mesencephalic junction dysplasia syndrome is a rare neurogenetic disorder reported to be caused by variants in several genes. Phenotypic presentation is characterized by clinical findings including developmental delay, hypotonia, spasticity, and dyskinetic movements in combination with distinctive imaging features on brain magnetic resonance imaging (MRI). Methods:Whole exome sequencing was conducted to unveil the molecular etiology of patients presenting with neurological manifestations from two unrelated families. Results:To the best of our knowledge, here we report the third family affected with diencephalic-mesencephalic junction dysplasia caused by a novel variant in GSX2and two siblings with a PCDH12variant exhibiting a less severe phenotype. The siblings with a PCDH12variant were positioned at the milder end of the phenotypic spectrum. Although both exhibited a clinical phenotype resembling cerebral palsy, one showed partial fusion of the hypothalamus and mesencephalon, whereas MRI was unremarkable in the other. Biallelic GSX2variants have been implicated in basal ganglia agenesis, and similarly, our patients had basal ganglia hypoplasia along with hypothalamic-mesencephalic fusion. Conclusion:Identifying variants associated with the syndrome in different genes will contribute to genotype-phenotype correlation.

Nurses are often the first to observe maltreatment and identify potential symptoms of this disorder. Proper vigilance, assessment, and mitigation strategies are essential to prioritize the well-being of dependents.Nurses are often the first to observe maltreatment and identify potential symptoms of this disorder. Proper vigilance, assessment, and mitigation strategies are essential to prioritize the safety of dependents.

Nurses are often the first to observe maltreatment and identify potential symptoms of this disorder. Proper vigilance, assessment, and mitigation strategies are essential to prioritize the well-being of dependents. Nurses are often the first to observe maltreatment and identify potential symptoms of this disorder. Proper vigilance, assessment, and mitigation strategies are essential to prioritize the safety of dependents. [ABSTRACT FROM AUTHOR]

Introduction:Kniest dysplasia is a rare skeletal disorder, characterized by mild dysmorphic features, cleft palate, short stature, short limbs, prominent joints, restricted joint mobility, hearing impairment, and ocular manifestations such as high-degree myopia, retinal detachment, and cataract. Typical radiological findings include platyspondyly, coronal clefts, and dumbbell-shaped long tubular bones. Case Presentation:Herein, we report on an 8-month-old boy who was referred to the pediatric genetic department due to narrow thorax and short extremities. He had mild dysmorphic features, cleft palate, narrow thorax, short extremities, and short stature. On radiographies, platyspondyly, hemivertebra, and dumbbell-shaped long tubular bones were detected. Clinical and radiological findings were consistent with Kniest dysplasia. Clinical exome sequencing was performed and revealed a heterozygous, pathogenic c.905C>T (p.Ala302Val) variant in the COL2A1gene, confirming the initial clinical diagnosis. Discussion:Kniest dysplasia is a very rare skeletal dysplasia, and an accurate clinical diagnosis is important to provide the best possible follow-up.

Introduction:Focal dermal hypoplasia (FDH) is a genodermatosis also known as Goltz-Gorlin syndrome caused by pathogenic variants in the PORCNgene and inherited in an X-linked dominant manner. Given the course of X-linked dominant inheritance, affected males can only survive in the state of mosaicism for a PORCNpathogenic variant or in the presence of XXY karyotype. FDH is a multisystemic disorder in which cutaneous, ocular, and skeletal systems are primarily affected. Patients also may display intellectual disability and central nervous system abnormalities, yet most may have normal mental development. Case Presentation:We report on a currently 11-year-old female patient with a novel missense heterozygous PORCNvariant who exhibited classical ectodermal, skeletal, and ocular findings in addition to mild intellectual disability, left-side diaphragm eventration, and puberty precox, a finding yet unreported in the literature. Conclusion:With this report, we aimed to expand the mutational spectrum and give insight into the importance of neurologic and skeletal system evaluation among other clinical features of FDH. Although gastrointestinal and genitourinary problems can occur during the course of the disease, to our knowledge, left-side diaphragm eventration and puberty precox are new features that have not been reported previously.

Introduction:Gorlin syndrome is a rare, autosomal dominant multi-systemic disorder with a predisposition to the development of cancers such as medulloblastoma and nevoid basal cell carcinoma. Heterozygous pathogenic variants in PTCH1are responsible for 90% of Gorlin syndrome cases. Pathogenic variants in PTCH1cause overstimulation of the sonic hedgehog signaling pathway, which plays a role in the development of embryonic structures and tumorigenesis. Clinical major and minor diagnostic criteria for Gorlin syndrome have been determined. Odontogenic keratocyst (OKC) is the most common reason for medical admission in Gorlin syndrome. In this article, it is aimed to draw attention to the fact that patients with Gorlin syndrome are not very rare in our country and the variability in phenotypic and dysmorphic findings may be a clue for the diagnosis. Methods:Exome sequencing was performed on the Illumina NextSeq550 System platform by using the Ion Ampliseq exome RDY kit for Illumina. Sanger sequencing was performed accordingly for the other affected individuals in both families. Results:In this study, the clinical and molecular findings of 9 Gorlin syndrome patients from three unrelated families are presented. Macrocephaly, calcification of falx cerebri, palmar-plantar pits, rib anomalies, and OKC were detected in decreasing order in more than half of the patients. A novel heterozygous frameshift PTCH1variant in family 1, a nonsense previously reported PTCH1variant in family 2, and a novel heterozygous splice-site PTCH1variant in family 3 were detected. Conclusion:Gorlin syndrome should be kept in mind in patients presenting with macrocephaly, palmoplantar pits, and OKC history. Careful examination of all family members is essential in the timely diagnosis of other affected individuals with minor phenotypic findings.

Introduction:Primrose syndrome (PS; MIM #259050) is a rare autosomal dominant genetic condition characterized by macrocephaly with or without tall stature, hypotonia, moderate to severe intellectual disability (ID) with delay in expressive speech development, behavioral abnormalities, and a recognizable facial phenotype including deep set eyes, ptosis, narrow and frequently downslanting palpebral fissures, and depressed nasal bridge. PS is caused by a heterozygous pathogenic variant in ZBTB20(MIM #606025) on chromosome 3q13. Among other characteristic findings are ocular abnormalities, hearing loss, calcification of the external ear cartilage, nonspecific brain magnetic resonance imaging findings, and cryptorchidism. Adults may exhibit joint contractures, distal muscle wasting, sparse body hair, cataract, and disturbed glucose metabolism as well. The majority of affected individuals have typically been adults until recently since the phenotype becomes more recognizable in time. Case Presentation:In this study, we report on a 14-month-old girl who presented with neurodevelopmental findings, facial features, and hearing loss. The glucose metabolism was normal, and muscle atrophy, joint contractures, and external ear cartilage calcification were yet hitherto not evident. A novel de novo missense variant in ZBTB20was identified with the aid of exome sequencing. Conclusion:PS is a rare clinical entity with various recognizable features, yet the phenotype may be indistinguishable from other neurodevelopmental disorders. Exome sequencing is a useful diagnostic tool especially in patients with no specific diagnosis despite detailed examinations and imaging studies.

Magnetic properties of materials ranging from conventional ferromagnetic metals to strongly correlated materials such as cuprates originate from Coulomb exchange interactions. The existence of alternate mechanisms for magnetism that could naturally facilitate electrical control has been discussed theoretically1–7, but an experimental demonstration8in an extended system has been missing. Here we investigate MoSe2/WS2van der Waals heterostructures in the vicinity of Mott insulator states of electrons forming a frustrated triangular lattice and observe direct evidence of magnetic correlations originating from a kinetic mechanism. By directly measuring electronic magnetization through the strength of the polarization-selective attractive polaron resonance9,10, we find that when the Mott state is electron-doped, the system exhibits ferromagnetic correlations in agreement with the Nagaoka mechanism.

Introduction:Mowat-Wilson syndrome (MWS) is an autosomal-dominant complex developmental disorder characterized by distinctive facial appearance, intellectual disability, epilepsy, and various clinically heterogeneous abnormalities reminiscent of neurocristopathies. MWS is caused by haploinsufficiency of ZEB2due to heterozygous point mutations and copy number variations. Case Presentation:We report on two unrelated affected individuals with novel ZEB2indel mutations, molecularly confirming the diagnosis of MWS. Quantitative real-time polymerase chain reaction (PCR) for the comparison of total transcript levels and allele-specific quantitative real-time PCR were also performed and demonstrated that the truncating mutations did not lead to nonsense-mediated decay as expected. Conclusion:ZEB2encodes a multifunctional pleiotropic protein. Novel mutations in ZEB2should be reported in order that genotype-phenotype correlations might be established in this clinically heterogeneous syndrome. Further cDNA and protein studies may help elucidate the underlying pathogenetic mechanisms of MWS since nonsense-mediated RNA decay was found to be absent in only a few studies including this study.

This manuscript discusses intimate partner violence as it occurs among adults and adolescents. With ongoing support and encouragement, a victim can often find support and strength to leave and live a normal, safe life.This manuscript discusses intimate partner violence as it occurs among adults and adolescents. With support and encouragement, a victim can find the strength to leave and live a safer life.

This manuscript discusses intimate partner violence as it occurs among adults and adolescents. With ongoing support and encouragement, a victim can often find support and strength to leave and live a normal, safe life. This manuscript discusses intimate partner violence as it occurs among adults and adolescents. With support and encouragement, a victim can find the strength to leave and live a safer life. [ABSTRACT FROM AUTHOR]

Introduction:3M syndrome is an autosomal recessive disorder characterized by characteristic facial features, severe pre- and postnatal growth restriction (<–4 SDS), and normal mental development. 3M syndrome is genetically heterogeneous. Up to date, causative mutations have been demonstrated in 3 genes, cullin-7 (CUL7), obscurin-like 1 (OBSL1), and coiled coil domain containing protein 8 (CCDC8). Case presentation:Here, we report a patient who was referred to our clinic due to short stature and developmental delay. Physical examination revealed prenatal onset short stature, low birth weight, and normal head circumference. She displayed several dysmorphic facial features in addition to developmental delay and bilateral sensorineural hearing loss. The physical findings were suggestive of 3M syndrome. Genetic assessment revealed a novel homozygous frameshift c.418_419delAC (p.Thr140Cysfs*11) variant in the CUL7gene and a previously reported pathogenic nonsense homozygous c.942C>A (p.Cys314Ter) variant in the ILDR1gene. The parents were heterozygous for the same variant. Discussion:3M syndrome should be considered in the differential diagnosis of patients with short stature and typical facial features even if in the presence of other inconsistent features such as developmental delay. In addition, it is important to take into account the co-occurrence of rare autosomal recessive genetic disorders especially in countries with a high consanguineous marriage rate.

BackgroundMonitoring disease progression in childhood interstitial lung diseases (chILD) is essential. No information for the minimal important difference (MID), which is defined as the smallest change in a parameter that is perceived as important prompting a clinician to change the treatment, is available. We calculated MIDs for vital signs (respiratory rate, peripheral oxygen saturation in room air, Fan severity score) and health-related quality of life (HrQoL) scores.MethodsThis study used data from the Kids Lung Register, which is a web-based management platform that collects data of rare paediatric lung disorders with a focus on chILD. Data of vital signs and HrQoL scores (Health Status Questionnaire, chILD-specific questionnaire and PedsQL V.4.0) were collected. MIDs were calculated according to distribution-based (one-third SD) and anchor-based methods (using forced expiratory volume in 1 s and forced vital capacity) as anchors.ResultsBaseline data of 774 children were used to calculate the following MIDs: respiratory rate 1.3 (z-score), O2saturation in room air 3.0%, Fan severity score 0.2–0.4, Health Status Questionnaire 0.4–0.8, chILD-specific questionnaire 4.4%–8.2%, physical health summary score 7.8%–8.9%, psychosocial health summary score 3.4%–6.9% and total score 5.1%–7.4%. Results of the responsiveness analysis generally agreed with the MIDs calculated.ConclusionsFor the first time, we provide estimates of MIDs for vital signs and HrQoL scores in a large cohort of chILD using different methods.

Objective Oculoauriculovertebral spectrum (OAVS) is a genetically and clinically heterogeneous disorder that occurs due to a developmental field defect of the first and second pharyngeal arches. Even though recent whole exome sequencing studies (WES) have led to identification of several genes associated with this spectrum in a subset of individuals, complete pathogenesis of OAVS remains unsolved. In this study, molecular genetic etiology of OAVS was systematically investigated.Design/Setting/Patients A cohort of 23 Turkish patients with OAVS, referred to Hacettepe University Hospital, Department of Pediatric Genetics from 2008 to 2018, was included in this study. Minimal diagnostic criteria for OAVS were considered as unilateral microtia or hemifacial microsomia with preauricular skin tag. The cohort was clinically reevaluated for craniofacial and extracranial findings. Molecular etiology was investigated using candidate gene sequencing following copy number variant (CNV) analysis. WES was also performed for 2 of the selected patients.Results Patients in the study cohort presented similar demographic and phenotypic characteristics to previously described patients in the literature except for a higher frequency of bilaterality, cardiac findings, and intellectual disability/developmental delay. CNV analysis revealed a possible genetic etiology for 3 patients (13%). Additional WES in 1 of the 2 patients uncovered a novel heterozygous nonsense variant in Elongation factor Tu GTP-binding domain-containing 2 (EFTUD2) causing mandibulofacial dysostosis with microcephaly (MFDM), which clinically overlaps with OAVS.Conclusion Detailed clinical evaluation for any patient with OAVS is recommended due to a high rate of accompanying systemic findings. We further expand the existing genetic heterogeneity of OAVS by identifying several CNVs and a phenotypically overlapping disorder, MFDM.

Diminished ovarian reserve (DOR) presents a complex challenge in the field of infertility, with factors like age and genetics traditionally under scrutiny. However, the potential influence of adverse childhood experiences on ovarian reserve remains a relatively unexplored area. This research aims to contribute novel insights to the understanding of diminished ovarian reserve etiology, shedding light on previously unexplored risk factors and their potential implications.

Purpose: Hedonic behavior is a well-known phenomenon for tourism activities by the nature of tourism itself. However, there is a possible conflict between the structure of halal tourism and hedonic behavior. This paper aims to investigate the hedonic perception levels of halal-sensitive tourists (HSTs) while questioning their travel motivations. Design/methodology/approach: According to the aim of this study, quantitative approach has been adopted via data gathering within World Halal Summit. A total of 1,123 surveys were gathered face to face from participants. Factor analysis applied to confirm validity of the data set while also running Cronbach alpha test through all dimensions. Also, frequency and mean analyses were applied in addition to t-test for comparing tests. Findings: Results briefly show that HSTs have an average level of perception of hedonism. They also travel once or twice a year for religious, social or environmental reasons which supports the finding about their hedonism perception. Research limitations/implications: The research is also important in the applied field, especially in terms of decision-makers and supply determinants in destination management. Because if it is determined that the HSTs exhibit a utilitarian consumption, it has a guiding feature for the decision-makers to prefer halal tourism in terms of environmental management in the destination. In terms of the economic sustainability of the research destination or businesses, it also serves as a guide for the supply determinants in their investment activities. Originality/value: This research is considerably important in terms of putting the HST typology on a conceptual basis in the theoretical field. In the research, it is tested whether the HSTs are hedonic consumers; in other words, whether they comply with the Islamic religious prohibitions. The tendency of HSTs to comply with the prohibitions reveals that they are utilitarian consumers, while halal tourism is a responsible tourism that cares about sustainability.

The congenital bone marrow failure syndrome Diamond-Blackfan anemia (DBA) is typically associated with variants in ribosomal protein (RP) genes impairing erythroid cell development. Here we report multiple individuals with biallelic HEATR3 variants exhibiting bone marrow failure, short stature, facial and acromelic dysmorphic features, and intellectual disability. These variants destabilize a protein whose yeast homolog is known to synchronize the nuclear import of RPs uL5 (RPL11) and uL18 (RPL5), which are both critical for producing ribosomal subunits and for stabilizing the p53 tumor suppressor when ribosome biogenesis is compromised. Expression of HEATR3 variants or repression of HEATR3 expression in primary cells, cell lines of various origins, and yeast models impairs growth, differentiation, pre–ribosomal RNA processing, and ribosomal subunit formation reminiscent of DBA models of large subunit RP gene variants. Consistent with a role of HEATR3 in RP import, HEATR3-depleted cells or patient-derived fibroblasts display reduced nuclear accumulation of uL18. Hematopoietic progenitor cells expressing HEATR3 variants or small-hairpin RNAs knocking down HEATR3 synthesis reveal abnormal acceleration of erythrocyte maturation coupled to severe proliferation defects that are independent of p53 activation. Our study uncovers a new pathophysiological mechanism leading to DBA driven by biallelic HEATR3 variants and the destabilization of a nuclear import protein important for ribosome biogenesis.

Nurses can use this tool for change in a variety of situations to help patients learn to live healthier lives.Nurses can use this tool for change in a variety of situations to help patients learn to live healthier lives.

Nurses can use this tool for change in a variety of situations to help patients learn to live healthier lives. [ABSTRACT FROM AUTHOR]

IntroductionAcute exacerbations (AEs) increase morbidity and mortality of patients with chronic pulmonary diseases. Little is known about the characteristics and impact of AEs on children's interstitial lung disease (chILD).MethodsThe Kids Lung Register collected data on AEs, the clinical course and quality of life (patient-reported outcomes - PRO) of rare paediatric lung diseases. Characteristics of AEs were obtained.ResultsData of 2822 AEs and 2887 register visits of 719 patients with chILD were recorded. AEs were characterised by increased levels of dyspnoea (74.1%), increased respiratory rate (58.6%) and increased oxygen demand (57.4%). Mostly, infections (94.4%) were suspected causing an AE. AEs between two register visits revealed a decline in predicted FEV1 (median −1.6%, IQR −8.0 to 3.9; p=0.001), predicted FVC (median −1.8%, IQR −7.5 to 3.9; p=0.004), chILD-specific questionnaire (median −1.3%, IQR −3.6 to 4.5; p=0.034) and the physical health summary score (median −3.1%, IQR −15.6 to 4.3; p=0.005) compared with no AEs in between visits. During the median observational period of 2.5 years (IQR 1.2–4.6), 81 patients died. For 49 of these patients (60.5%), mortality was associated with an AE.ConclusionThis is the first comprehensive study analysing the characteristics and impact on the clinical course of AEs in chILD. AEs have a significant and deleterious effect on the clinical course and health-related quality of life in chILD.

BackgroundNo data on healthcare utilisation and associated costs for the many rare entities of children’s interstitial lung diseases (chILD) exist. This paper portrays healthcare utilisation structures among individuals with chILD, provides a pan-European estimate of a 3-month interval per-capita costs and delineates crucial cost drivers.MethodsBased on longitudinal healthcare resource utilisation pattern of 445 children included in the Kids Lung Register diagnosed with chILD across 10 European countries, we delineated direct medical and non-medical costs of care per 3-month interval. Country-specific utilisation patterns were assessed with a children-tailored modification of the validated FIMA questionnaire and valued by German unit costs. Costs of care and their drivers were subsequently identified via gamma-distributed generalised linear regression models.ResultsDuring the 3 months prior to inclusion into the registry (baseline), the rate of hospital admissions and inpatient days was high. Unadjusted direct medical per capita costs (€19 818) exceeded indirect (€1 907) and direct non-medical costs (€1 125) by far. Country-specific total costs ranged from €8 713 in Italy to €28 788 in Poland. Highest expenses were caused by the disease categories ‘diffuse parenchymal lung disease (DPLD)-diffuse developmental disorders’ (€45 536) and ‘DPLD-unclear in the non-neonate’ (€47 011). During a follow-up time of up to 5 years, direct medical costs dropped, whereas indirect costs and non-medical costs remained stable.ConclusionsThis is the first prospective, longitudinal study analysing healthcare resource utilisation and costs for chILD across different European countries. Our results indicate that chILD is associated with high utilisation of healthcare services, placing a substantial economic burden on health systems.

The prevalence of neurodegenerative diseases is increasing globally, with an imperativeneed to identify and expand the availability of pharmaceutical treatment strategies. Alzheimer's diseaseis the most common neurodegenerative disease for which there is no cure and limited treatments.Rodent models are primarily used in Alzheimer's disease research to investigate causes, pathology,molecular mechanisms, and pharmaceutical therapies. However, there is a lack of a comprehensiveunderstanding of Alzheimer's disease causes, pathogenesis, and optimal treatments duein part to some limitations of using rodents, including higher economic cost, which can influencesample size and ultimately statistical power. It is necessary to expand our animal model toolbox toprovide alternative strategies in Alzheimer's disease research. The zebrafish application in neurodegenerativedisease research and neuropharmacology is greatly expanding due to several vitalstrengths spanning lower economic costs, the smaller size of the organism, a sequenced characterizedgenome, and well described anatomical structures. These characteristics are coupled to the conservedmolecular function and disease pathways in humans. The existence of orthologs for genes associatedwith Alzheimer's disease in zebrafish is also confirmed. While wild-type zebrafish appearto lack some of the neuropathological features of Alzheimer's disease, the advent of genetic editingtechnologies has expanded the evaluation of the amyloid and neurofibrillary tangle hypotheses usingthe zebrafish and exploration of pharmaceutical molecular targets. An overview of how genetic editingtechnologies are being used on the zebrafish to create models to investigate the causes, pathology,molecular mechanisms, and pharmaceutical targets of Alzheimer's disease is detailed.

Turner syndrome (TS) is one of the most common malformation syndromes in females. A total number of 107 TS patients, diagnosed between 2000 and 2018, were evaluated for their phenotypic features, and cardiac and renal findings. The mean age of patients at admission was 10.08 ± 4.9 years (range, newborn to 18 years). Four different karyotype groups were encountered, and the most common findings in all groups were short stature, followed by cubitus valgus. Echocardiographic findings of 85 patients were available among which 63 (n= 63/85, 74.1%) were found to be normal. The most common cardiac anomaly was left ventricular outflow tract/aortic arch pathology detected in 9 patients (n= 9/22, 40.9%). Renal malformations were detected in 15 patients (n= 15/84, 17.9%) by renal ultrasonography, and horseshoe kidney was the most common renal malformation, followed by left multicystic dysplastic kidney. There was no significant difference in the frequency of renal malformation and cardiac anomalies among the 4different karyotype groups (χ2 exact test, p> 0.05). Compared with the literature, the frequency of renal anomalies was detected at a lower rate. Karyotype analysis should be carried out in all female patients with short stature, even if there are no associated phenotypic findings suggestive of TS. Since cardiac anomalies are frequently seen in TS patients and they represent a common cause of mortality, echocardiography should be carried out as soon as the definite diagnosis is established. Renal anomalies may be less frequent than cardiac anomalies; however, evaluation of TS patients with renal ultrasonography should be done at the time of diagnosis. Although renal ultrasonography can be used as the initial renal screening in TS patients, it may underestimate the frequency of renal malformation; hence, further management may be required.

Acromesomelic dysplasia type Maroteaux (AMDM, OMIM #602875) is an autosomal recessive disorder characterized by severe short stature, shortened middle and distal segments of the limbs, redundant skin of fingers, radial head subluxation or dislocation, large great toes and cranium, and normal intelligence. Only the skeletal system appears to be consistently affected. AMDM is caused by biallelic loss-of-function variants in the natriuretic peptide receptor B (NPRBor NPR2, OMIM #108961) which is involved in endochondral ossification and longitudinal growth of limbs and vertebrae. In this study, we investigated 26 AMDM patients from 22 unrelated families and revealed their genetic etiology in 20 families, via Sanger sequencing or exome sequencing. A total of 22 distinct variants in NPR2(14 missense, 5 nonsense, 2 intronic, and 1 one-amino acid deletion) were detected, among which 15 were novel. They were in homozygous states in 19 patients and in compound heterozygous states in four patients. Parents with heterozygous NPR2variants were significantly shorter than the control. Extra-skeletal abnormalities, including global developmental delay/intellectual disability, nephrolithiasis, renal cyst, and oligodontia were noted in the patient cohort. The high parental consanguinity rate might have contributed to these findings, probably associated with other gene variants. This study represents the largest cohort of AMDM from Turkey and regional countries and further expands the molecular and clinical spectrum of AMDM.

Dysosteosclerosis (DOS) is a rare sclerosing bone dysplasia characterized by osteosclerosis and platyspondyly. DOS is genetically heterogeneous and causally associated with mutations in three genes, SLC29A3, CSF1R,and TNFRSF11A. TNFRSF11Ahas been known as the causal gene for osteopetrosis, autosomal recessive 7, and is recently reported to cause DOS in three cases, which show a complex genotype-phenotype relationship. The phenotypic spectrum of TNFRSF11A-associated sclerosing bone dysplasia remains unclear and needs to be characterized further in more cases with molecular genetic diagnosis. Here, we report another TNFRSF11A-associated DOS case with a homozygous missense mutation (p.R129C). The mutation effect is different from the previous three cases, in which truncated or elongated RANK proteins were generated in isoform specific manner, thus enriching our understanding of the genotype-phenotype association in TNFRSF11A-associated sclerosing bone dysplasia. Besides DOS, our case presented with intracranial extramedullary hematopoiesis, which is an extremely rare condition and has not been identified in any other sclerosing bone dysplasias with molecular genetic diagnosis. Our findings provide the fourth case of TNFRSF11A-associated DOS and further expand its phenotypic spectrum.

Growth failure and inadequate weight gain are common problems in childhood interstitial lung diseases (chILD) and these children usually need high calories. It is important to manage both pulmonary functions and nutrition as part of their overall treatment plan and early interventions will help children to improve their quality of life and slow the progression of chronic lung disease. Nutritional evaluation on routine clinical follow-up is important, although there are not any specific guidelines for chILD. Nutritional education, high balanced energy, protein, and fat diet will assist to improve weight gain and maintenance of adequate nutrition status in children with ILD.

The RASopathies are a group of clinically and genetically heterogeneous developmental disorders caused by dysregulation of the RAS/MAPK signalling pathway. Variants in several components and regulators of this pathway have been identified as the pathogenetic cause. In 2015, missense variants in A2ML1were reported in three unrelated families with clinical diagnosis of Noonan syndrome (NS) and a zebrafish model was presented showing heart and craniofacial defects similar to those caused by a NS-associated Shp2 variant. However, a causal role of A2ML1variants in NS has not been confirmed since. Herein, we report on 15 individuals who underwent screening of RASopathy-associated genes and were found to carry rare variants in A2ML1, including variants previously proposed to be causative for NS. In cases where parental DNA was available, the respective A2ML1variant was found to be inherited from an unaffected parent. Seven index patients carrying an A2ML1variant presented with an alternate disease-causing genetic aberration. These findings underscore that current evidence is insufficient to support a causal relation between variants in A2ML1and NS, questioning the inclusion of A2ML1screening in diagnostic RASopathy testing.

Females take place in advertisements for different reasons and using them as sexual appeal content is one of them. Like all other industries, advertisers use females in advertisements and this causes the objectification of female which brings some negative consequences such as stereotypes against women and approve of violence against them in the tourism industry. It also marginalises women out of society by creating a perception as they belong to men and men's pleasure by serving them. There are numerous researches about this topic. However this research aims to explore the existence of objectification of females in tourism related advertisements by investigating hotels' picture galleries which are setup to promote hotels to their potential customers. Since nudity and sexuality are subjective terms, contents from literature and two different image sets are used to strengthen the discussion of this paper. Findings present how females become objects of sexual appeal in 5-star hotels' images.