Congenital Malformations Research Articles

Characteristics and maternal-fetal outcomes of pregnant women with critical congenital heart disease from a single center in China

Objective: To summarize the characteristics of pregnant women with critical congenital heart disease, and to explore continuous, integrated, multidisciplinary management for this segment of population. Methods: The clinical records of pregnant women with severe congenital heart disease with a history of intensive care who were treated in Guangdong Provincial People's Hospital from January 1, 2008 to December 31, 2020 were retrospectively analyzed. Results: (1) A total of 132 cases were included, including 128 pregnant women [gestational age (28.0±8.8) weeks] and 4 puerpera cases (6-32 days postpartum), 63.6% (84/132) from economic underdeveloped rural areas, and 78.0% (103/132) by the municipal hospital, irregular prenatal examination accounted for 59.1% (78/132). The main type of congenital heart disease was shunt lesion (55.3%, 73/132). 90.9% (120/132) with mWHO risk classification stage Ⅳ were assigned to it. The main cardiovascular complication was pulmonary hypertension (64.4%, 85/132). 46.2% (61/132) of the patients had been diagnosed with congenital heart disease before pregnancy, and 70.5% (93/132) of the patients had not received any treatment before pregnancy. (2) All patients received obstetric-led, multidisciplinary care. The rescue success rate was 96.2% (127/132), and no serious obstetric complications occurred. The mortality within 24 hours after discharge was 3.8% (5/132). 16.7% (22/132) underwent cardiac surgery during pregnancy, of which 77.3% (17/22) continued their pregnancy beyond 34 weeks. Totally, the delivery week was (30.5±8.6) weeks, and the main mode was cesarean section (71.2%, 94/132). The average weight of 99 live births (including 1 twin pregnancy) was (2 167±698) g. Preterm birth, fetal growth restriction, and congenital malformations were the main fetal comorbidities. Conclusions: Pregnant women with severe congenital heart disease mainly come from areas with underdeveloped economic and medical levels. Later disease intervention, pregnancy retention despite of clear pregnancy contraindications are the distinctive features, which leaded to a significant increase of incidence of maternal and fetal complications, and an increase of the consumption of medical resources. Multidisciplinary active treatment and cardiac surgery during pregnancy could relatively improve maternal and fetal pregnancy outcomes.

Clinical and epidemiological characteristics of disabling neurological diseases (literature review)

Disabling neurological diseases are accompanied by disturbances in motor activity, sensitivity, cognitive impairment and chronic pain, often reduce the quality of life in its last years and months, cause death, and therefore they are proposed to be considered as palliative diseases. To determine the list of these diseases, we made a selection from the analytical report of the Global Burden of Disease Study for 1990–2010, published in the Lancet journal in 2012. Of 289 disabling diseases, based on the criteria of direct or frequent comorbid damage to the nervous system, the presence of chronic pain, cognitive decline and limitation of motor activity, which are the causes of a significant decrease in the quality of life and work capacity, we chose the following diseases and pathological conditions: malignant neoplasms, AIDS, severe injuries, strokes, demyelinating diseases, epilepsy, depression and suicide, musculoskeletal disorders (neck, lower back pain, arthritis), tension headache, migraine, loss of vision and hearing, dementia of adults, severe and profound mental retardation of children, children’s cerebral palsy, congenital malformations. We studied the trend of increasing or decreasing the burden of selected diseases depending on the number of years lived with disability and analyzed the interpretation of these trends according to literary sources. Special attention in the review was paid to disabling neurological diseases, which are unjustifiably not considered in the health care systems of most countries as palliative: epilepsy, multiple sclerosis and dementia. The clinical and epidemiological characteristics of these diseases were also studied by the bibliosemantic method. The search for literature sources for the review was conducted in PubMed and Google Scholar. It is concluded that the treatment of patients with disabling neurological diseases as palliative patients, with appropriate organizational solutions in national health care systems, will help to improve the quality of life and reduce suffering of both patients and their family members.

Maternal and fetal factors for determining the cesarean section type (scheduled/emergency) in bitches

One hundred and forty bitches and their offspring (689 puppies) were involved in this study. The influence of different maternal features such as age, breed (brachycephalic/non-brachycephalic), previous births (primiparous/multiparous), health status (complete/incomplete) and litter size over the type of cesarean sections (scheduled/emergency), the neonatal survival, and the incidence of congenital malformations were also examined. Scheduled cesareans were predominant (104/140), of which 90 % were brachycephalic breeds and females were mostly between 2 and 4 years old (54.8 %), multiparous (88.4 %) and with a correct health status (67.3 %). Emergency cesarean sections mainly involved non-brachycephalic breeds (80 %) and were carried out mostly in females under 4 years of age (72.2 %), primiparous (77.7 %), with incomplete health status and a large litter size (47.2 %). Perinatal mortality was notably higher in emergency C-sections (3.25 % and 13.3 %, scheduled and emergency C-sections, respectively); the highest incidence of neonatal mortality was recorded in young females (<2, 2–4 years old), primiparous and with incomplete health status. Congenital anomalies were observed in 4.50 % (31/689) of the puppies, with anasarca (38.71 %) and cleft palate (29.03 %) being the most frequently observed malformations. A higher incidence of congenital malformations was detected in puppies from dams with incomplete sanitary health and from inbreeding cross. Overall, the study provides valuable insights into the complex interplay between maternal characteristics and cesarean outcomes. Appropriate genetic selection, good sanitary health conditions, and the age of the reproducers, are pivotal factors in planning for gestation and improving the survival of neonates.

Prenatal olanzapine exposure and congenital talipes equinovarus (clubfoot): a case report and review of emerging evidence

Recently, concerns have emerged about the potential teratogenic effects of olanzapine, particularly its association with congenital malformations such as congenital talipes equinovarus (clubfoot). Evidence from a large Finnish study, which reported a 2.5-fold increase in musculoskeletal anomalies, as well as various case reports, suggests a significant link between in-utero exposure to olanzapine and these anomalies. This case report aims to add to the growing body of evidence by detailing a new instance of clubfoot following prenatal olanzapine exposure. A 25-year-old woman suffering from bipolar I disorder with psychotic features was treated with olanzapine during pregnancy, resulting in the birth of a male infant with clubfoot but no other malformations. This case underscores the importance of careful risk assessment and monitoring for pregnant women undergoing psychiatric treatment with olanzapine. Potential mechanisms, such as disrupted fetal musculoskeletal development due to olanzapine’s pharmacological effects, warrant further investigation. Comparative analysis with other cases highlights consistent patterns, emphasizing the need for further research to elucidate the mechanisms and risk factors involved.

Medical Genetics in Brazil in the 21st Century: A Thriving Specialty and Its Incorporation in Public Health Policies.

Brazil is a continent-size country with 203 million inhabitants, classified as a developing upper-middle-income country, although inequities remain significant. Most of the population is assisted by the public Unified Health System (SUS), along with a thriving private health sector. Congenital malformations are the second leading cause of infant mortality and chronic/genetic disorders and a significant burden in hospital admissions. The past two decades have been crucial for formalizing medical genetics as a recognized medical specialty in the SUS, as well as for implementing a new health policy by the Ministry of Health for comprehensive care for rare diseases. These public health policies had the broad support of the Brazilian Society of Medical Genetics and Genomics and patient organizations. Most comprehensive genetic services are concentrated in large urban centers in the South and Southeast regions of Brazil; with this new policy, new services throughout the country are progressively being integrated. The number of medical geneticists increased by 103% in a decade. Details on the policy and an overview of the availability of services, testing, human resources, newborn screening, research projects, patient organizations, and relevant issues regarding medical genetics in this vast and diverse country are presented.

A Case Report of Aberrant Origin of the Right Coronary Artery from thePulmonary Artery in an Adult Male: The Role of Multi-modality Imaging

Background: The normal anatomy of the coronary arteries consists of the right coronary artery and the left main coronary artery, which originate from the right and left sinuses of Valsalva in the aortic root separately. In general, congenital anomalies of the coronary artery are uncommon in adults. The ectopic origin of a coronary artery from the pulmonary trunk is part of a group of infrequent coronary artery anomalies. The Anomalous origin of the Right Coronary Artery from the Pulmonary Artery (ARCAPA) is thought to be an extremely rare congenital coronary artery anomaly. Most of our knowledge and experience about this congenital coronary malformation is derived from published case reports and series. Case Presentation: We have, herein, reported the case of a 68-year-old male who was discovered to have ARCAPA after he presented to our center with chest pain. The patient underwent multiple invasive and non-invasive diagnostic imaging modalities, including an echocardiogram, a coronary angiogram, a multislice-gated coronary computed tomographic angiogram, and stress perfusion cardiovascular magnetic resonance imaging. The clinical decision was to continue with conservative non-surgical management along with close follow-up. Conclusion: The ARCAPA anomaly is considered to be one of the rare congenital coronary artery variances that can be discovered in late adulthood as a patient may remain asymptomatic for many decades.

Global burden and management of women with epilepsy in pregnancy: A modeling study

Most pregnant women with epilepsy do not receive proper medical care, which creates a special burden worldwide. We aimed to qualify this special global burden and assess the impact of different clinical management strategies to reduce it. The data used in this study were extracted from articles published between 2005 and 2022. We calculated the economic costs associated with major burdens experienced by pregnant women with epilepsy. We developed a microsimulation model to estimate the different effects of various interventions and their combinations as integrated strategies for pregnant women with epilepsy and related burden reduction. We also compared the regional differences in disease burden and interventions. The total economic burden for pregnant women with epilepsy is estimated to reach $1.8 billion globally annually, which is more than three times the burden for epilepsy alone. Folic acid supplementation is projected to be the most effective intervention, with a 9.1% reduction in major congenital malformations, a 14.9% reduction in autism spectrum disorder, and a 10.8% reduction in offspring-related economic burden globally annually. Integrated strategies are associated with a reduced economic burden of up to $37.7 million annually globally. Folic acid supplementation is the most effective intervention in high- and upper-middle-income countries, whereas changes in antiseizure medication prescriptions are more effective in lower-middle- and low-income countries. This study highlights the huge burden for pregnant women with epilepsy and actions that must be taken to improve their quality of life. This work was supported by the Sichuan Science and Technology Program (2023YFS0047).

Periodontal plastic surgery and regenerative periodontal surgery in a forty-seven-year-old patient with cleft lip and palate

Cleft lip and palate represent one of the most prevalent congenital malformations in humans, with an estimated prevalence of 0.45 per 1,000 individuals. During childhood and adolescence, affected patients undergo lengthy and complicated interdisciplinary treatment including treatment from specialists in pediatric medicine, oral and maxillofacial surgery, orthodontics, and otorhinolaryngology. The patient exhibited scarred adhesions with localized mucogingival deformities of the premaxilla (region 12 − 11), bilateral cleft lip and palate, and a complex underlying one-wall intrabony osseous defect on tooth 11, in addition to hard- and soft-tissue deficiencies at the dental implant in region 12. Following the administration of localized anti-infective periodontal therapy, regenerative periodontal surgery, regenerative surgical therapy of periimplantitis, and periodontal plastic surgery were performed. This resulted in a long-term, stable improvement in the clinical situation. Regenerative periodontal therapy and periodontal plastic surgery in patients with palato-alveolar cleft present a significant challenge due to the poor condition of the mucosa and gingiva adjacent to the defect and the insufficient bone dimensions. For this reason, it seems beneficial to include the periodontist in the interdisciplinary treatment team of a patient with cleft lip and palate from the outset. It is recommended that the patient be provided with dental prophylaxis measures and receive individualized oral hygiene instructions in addition to the main maxillofacial and orthodontic treatment. This approach would facilitate the identification of mucogingival issues at an early stage and the implementation of appropriate treatment.

Formation of the Mandibular Condylar Cartilage in Human Specimens Between 10 and 15 Weeks of Gestation

Background: The study examines some morphological and histological factors that may contribute to condylar cartilage (CC) formation. The specimens used were consecutive sections obtained from 20 human fetuses ranging in age from 10 to 15 weeks. The vascular canals (VC) emerge in the CC and initiate the process of intramembranous ossification. The mandibular condylar cartilage is crucial for the growth and function of the mandible, and it also contributes to the development of the Temporomandibular joint. Understanding the development of mandibular condylar cartilage throughout the early stages of gestation is essential for detecting congenital craniofacial deformities. Objectives: Examine the stages of MCC development in human samples from fetuses at 10-15 weeks of gestation. Study Design: A descriptive Cross-sectional Study. Place and Duration of Study: Department of Anatomy and Obstetric Nowshera Medical College from 15th Nov 2020 to 1st Jun 2021. The changes in the shape and size of the bones and the processes of bone formation should also be determined. Methods: The current study is descriptive, cross-sectional, and involves post-mortem human fetal specimens aged 10-15 weeks. The specimens were obtained from the Department of Obstetrics of QHAMC after miscarriages and intrauterine deaths. The absence of external and congenital malformations was verified. Light microscopic and histological assessment was done with the aid of H&amp;E-stained sections. Results : Twenty fetal specimens were used in the study, with an average gestation period of 12. 5 weeks (±1. 5 weeks). Histological analysis revealed gradual chondrocyte maturation and the beginning of the ossification process. At ten weeks, MCC was comprised of undifferentiated mesenchymal cells. At twelve weeks, it is possible to observe the differentiation of chondrocytes and early ossification. At 15 weeks, the ossification stages of the CRL were at a superior level with the hypertrophic chondrocytes and mineralized cartilage. The p-values for differences in developmental stages between the gestational ages were less than 0. Hence, the differences were statistically significant. Conclusion: The MCC in human specimens at 10–15 weeks' gestation undergoes considerable morphological transformation and commences the ossification process. Knowledge of these stages is essential in identifying and intervening in congenital craniofacial disorders. The authors recommend that future studies focus on investigating molecular processes that may contribute to the development of MCC. Keywords: Mandibular condylar cartilage, Development, Gestation, Ossification

Monosymmetros Cephalothoracopagus Tetrabrachius and Tetrapus Piglets with Syndromic Evolution.

Conjoined twins are rare congenital malformations that have been reported in mammals. Two different cases are presented in this study. Case No. 1 features monocephalic, thoracopagus-conjoined twin piglets with anencephaly and palatoschisis of the Pietrain breed, and case No. 2 features monocephalic, thoracopagus conjoined twin piglets with palatoschisis and bifid root tongue of a mixed breed. These cases were examined using post-mortem and computed tomography (CT) examinations. In both cases, the conjoined symmetrical twins had a single head, one neck, and fused thoracic cavities, while the abdominal cavities were separated. Similarly, in both cases, they had four forelimbs and four hindlimbs and duplicated foramen magnum. During CT examination, in case No. 1, severe abnormalities were observed in the skull and vertebral column. In the left twin, occult dysraphism was seen from the C2 vertebra until the end of the vertebral column, and in the right twin, from the C3 vertebra until the end of the state vertebral level. In case No. 2, the oral cavity contained a tongue with a bifid root connected with one hyoid bone, and the soft palate presented a small cleft. During CT examination, the parietal bone and the occipital bones were partially duplicated. This case also presented occult dysraphism, but only in the cervical vertebrae, C1-C6 for the left twin and C1-C5 for the right twin. In both cases, abnormalities of the internal organs were revealed during necropsy. Conjoined twins with multiple congenital anomalies presented here enhance our understanding of the various clinical forms of conjoined cases in veterinary medicine.

Prevalence and classification of congenital thoracic vertebral body abnormalities in neurologically normal brachycephalic 'screw-tail' dog breeds in referral practice in Australia.

To evaluate the prevalence, type, site and breed predisposition of thoracic congenital vertebral malformations (CVM) in neurologically normal brachycephalic 'screw-tail' dog breeds. Retrospective case series. Neurologically normal French Bulldogs (n = 63), British Bulldogs (n = 42), Boston Terriers (n = 4) and Pugs (n = 86) presenting for brachycephalic obstructive airway syndrome treatment. Either a plain computer tomography scan of the thorax or lateral and dorso-ventral digital radiographs of the thoracic vertebral column of each dog were assessed for any vertebral malformations and classed according to the Modified McMaster vertebral abnormality classification scheme proposed by Guiterrez et al. RESULTS: The prevalence of dogs with one or more abnormal vertebrae was 96.82% in French Bulldogs, 90.47% in British Bulldogs, and 76.74% in Pugs. Pugs had significantly lower instances of CVMs than French Bulldogs. The four Boston Terriers all had vertebral malformations, but the results were not considered to be statistically significant due to their small sample size. In French Bulldogs and British Bulldogs, ventral hypoplasia (Type 3) occurred at greater rates than all other types, followed by ventral and median hypoplasia (Types 7) and symmetrical hypoplasia (Type 8). In Pugs, symmetrical hypoplasia (Type 8) was the most common and then ventral hypoplasia (Type 3). The most affected vertebrae were T6-T9 in Pugs and T5-T10 in French Bulldogs and British Bulldogs. The majority of neurologically normal brachycephalic 'screw-tail' dogs assessed in this paper possessed one or more congenital thoracic vertebral malformations. Dogs with vertebral malformations were found to be more likely to have more than one affected vertebra. Sex had no effect on the prevalence of CVM. A substantial number of neurologically normal brachycephalic 'screw-tail' dogs suffer from congenital vertebral malformations. Thus, the need for selective breeding programmes to eliminate this hereditary condition is crucial.

Maternal Exposure to Ozone and the Risk of Birth Defects: A Time-Stratified Case-Crossover Study in Southwestern China.

A few studies have explored the relationship between air pollution exposure and the risk of birth defects; however, the ozone-related (O3) effects on preconception and first-trimester exposures are still unknown. In this time-stratified case-crossover study, conditional logistic regressions were applied to explore the associations between O3 exposure and the risk of birth defects in Chongqing, China, and stratified analyses were constructed to evaluate the modifiable factors. A total of 6601 cases of birth defects were diagnosed, of which 56.16% were male. O3 exposure was associated with an increased risk of birth defects, and the most significant estimates were observed in the first month before pregnancy: a 10 ug/m3 increase of O3 was related to an elevation of 4.2% [95% confidence interval (CI), 3.4-5.1%]. The associations between O3 exposure and congenital malformations and deformations of the musculoskeletal system were statistically significant during almost all exposure periods. Pregnant women with lower education and income, and from rural areas, were more susceptible to O3 exposure, with the strongest odds ratios (ORs) of 1.066 (95%CI, 1.046-1.087), 1.086 (95%CI, 1.034-1.140), and 1.053 (95%CI, 1.034-1.072), respectively. Our findings highlight the health risks of air pollution exposure and raise awareness of pregnant women's vulnerability and the susceptibility window period.

Endoscopic Surgery for Congenital or Acquired Cataract Associated with Persistent Fetal Vasculature: A Case Series.

Persistent fetal vasculature (PFV) is a congenital malformation caused by a failure in regression of the primary vitreous and hyaloid vessels. An abnormal PFV occurs in the anterior and posterior segments of the eye. Surgery for PFV carries the risk of retinal detachment. We report four cases of cataracts associated with PFV, in which our novel surgical technique with an intraocular endoscope was safely performed. Lensectomy and vitrectomy were performed in cases 1, 3, and 4, while lensectomy, vitrectomy, and intraocular lens implantation using an endoscope were performed in case 2. In all cases, after lens removal, a slit at the posterior lens capsule was created to avoid the retrolental fibrovascular membrane using underwater electric coagulation. Moreover, the endoscope was inserted, by which the intraocular region was observed to determine the treatment method for the fibrovascular membrane and vitreous stalk. No additional surgeries were required for complications before or after any of the surgeries. Using an endoscope during cataract surgery associated with PFV, observing the vitreous stalk at high magnification and ensuring safe treatment were possible. Endoscopic surgery could be considered an effective method for treating PFV-associated cataracts.

Multifaceted Roles of Nerve Growth Factor: A Comprehensive Review with a Special Insight into Pediatric Perspectives.

Nerve growth factor (NGF) is a neurotrophic peptide largely revealed for its ability to regulate the growth and survival of peripheral sensory, sympathetic, and central cholinergic neurons. The pro-survival and regenerative properties of neurotrophic factors propose a therapeutic potential in a wide range of brain diseases, and NGF, in particular, has appeared as an encouraging potential treatment. In this review, a summary of clinical studies regarding NGF and its therapeutic effects published to date, with a specific interest in the pediatric context, will be attempted. NGF has been studied in neurological disorders such as hypoxic-ischemic encephalopathy, traumatic brain injury, neurobehavioral and neurodevelopmental diseases, congenital malformations, cerebral infections, and in oncological and ocular diseases. The potential of NGF to support neuronal survival, repair, and plasticity in these contexts is highlighted. Emerging therapeutic strategies for NGF delivery, including intranasal administration as well as advanced nanotechnology-based methods, are discussed. These techniques aim to enhance NGF bioavailability and target specificity, optimizing therapeutic outcomes while minimizing systemic side effects. By synthesizing current research, this review underscores the promise and challenges of NGF-based therapies in pediatric neurology, advocating for continued innovation in delivery methods to fully harness NGF's therapeutic potential.

A new magnetic resonance imaging-based PUMCH classification system for congenital cervical malformations: devising a standardised diagnosis pathway

ObjectivesTo develop an innovative magnetic resonance imaging (MRI)-based PUMCH (Peking Union Medical College Hospital) classification system aimed at standardising the diagnosis of congenital cervical malformations (CCMs) by identifying their distinctive MRI features.MethodsSeventy-nine consecutive patients with CCM underwent pre-treatment pelvic MRI; three experienced gynaecological radiologists retrospectively analysed these images. Qualitative assessments included Rock et al’s classification; PUMCH classification; haematometra; cervical signal features; ovarian endometriosis; haematosalpinx; and uterine, vaginal, urinary, and musculoskeletal malformations. Quantitative assessments involved the uterine volume, sagittal cervical length, and maximum ovarian cross-sectional area. The surgical treatment types were also recorded. Statistical methods were used to incorporate differences in clinical features and surgical methods into our classification.ResultsMorphologically, CCMs were categorised into three types: type I (53%) was characterised by the presence of a cervix with visible cervical canals; type II (23%) featured an existing cervix with concealed cervical canals; and type III (24%) indicated cervical aplasia, which involves a blind end in the lower part of the uterine corpus. Haematometra was significantly more prevalent in patients with type I CCM than in those with type II (p < 0.001). There were three cervical signal patterns: no signal (27%), no evident layer differentiation (21%), and multi-layer differentiation with haematocele (52%). Most patients (94%) had complete vaginal atresia. Type I CCM patients had a higher likelihood of regaining normal uterovaginal anatomy compared to types II and III.ConclusionsOur proposed PUMCH classification system has a high potential for enhancing the efficiency of clinical diagnosis among patients with CCM.Critical relevance statementThe proposed new PUMCH classification promised to elevate the conventional diagnostic trajectory for congenital cervical malformations, offering a valuable framework to refine the selection and planning of surgical interventions, thereby enhancing overall clinical efficacy.Key PointsEffective classification of congenital cervical malformations is desirable to optimise the diagnostic process.We presented a PUMCH classification of congenital cervical malformations using pelvic MRI.The new classification significantly aids clinical triage for congenital cervical malformations.Graphical

Periconceptional maternal supplement intake and human embryonic growth, development, and birth outcomes: the Rotterdam Periconception Cohort.

Is periconceptional multiple-micronutrient supplement (MMS) use including folic acid (FA) compared to FA use only associated with increased embryonic growth, development, and birth weight in a high-risk population? Women with MMS intake show no significant differences in first-trimester morphological embryo development, but increased first-trimester embryonic growth trajectories and fewer neonates born small for gestational age (SGA), less than the 3rd percentile (<p3), compared to women using only FA. Periconceptional maternal FA intake in the general population is associated with increased embryonic and fetal growth, and reduced risks of neural tube defects, other congenital malformations, low birth weight, and neonates born SGA. A prospective tertiary hospital-based cohort study (the Rotterdam Periconceptional Cohort) was conducted from January 2010 to December 2020. We included 1076 women from the Rotterdam Periconceptional Cohort, before 10 weeks of pregnancy with follow-up until delivery. Embryonic growth was assessed by measurement of crown-rump length (CRL) and embryonic volume (EV), and embryonic morphology was described by Carnegie stages using longitudinal three-dimensional ultrasound scans and virtual reality techniques. Birth outcomes were extracted from medical records. General characteristics and supplement use were extracted from research questionnaires. This study showed increased embryonic growth trajectories (adjusted models, CRL: β = 0.052, 95% CI 0.012-0.090, EV: β = 0.022, 95% CI 0.002-0.042) in women using MMS compared to those using only FA. Moreover, a 45% reduced risk of a neonate-born SGA (<p3) was shown in women using MMS compared to FA users (adjusted OR = 0.546, 95% CI 0.308, 0.969). Embryonic morphological development (Carnegie stages) and the occurrence of miscarriages did not differ between women using MMS or solely FA. Following the heterogeneity of the composition and dose of MMS preparations, it is unclear which specific micronutrient, combination, or dose explains the increased embryonic growth trajectory and reduction in risk for SGA. This also hampers the possibility of differentiating between the effects of FA alone or as a component of MMS. Our findings emphasize the importance of periconceptional maternal MMS use as a potential preventative intervention against reduced embryonic growth and neonates born SGA. Therefore, we recommend the periconceptional use of MMS in women at risk of inadequate micronutrient intake. However, awareness of potentially harmful side effects of high doses and combinations of micronutrients is essential, therefore the optimal composition and dose need to be investigated, and careful surveillance is recommended. This research was funded by the Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands, and the ZonMw grant Open Competition 2018 (09120011910046). The authors declare that they have no conflict of interest. NTR4356.

Integrative analysis of bulk and single-cell RNA sequencing reveals the gene expression profile and the critical signaling pathways of type II CPAM

BackgroudType II congenital pulmonary airway malformation (CPAM) is a rare pulmonary microcystic developmental malformation. Surgical excision is the primary treatment for CPAM, although maternal steroids and betamethasone have proven effective in reducing microcystic CPAM. Disturbed intercellular communication may contribute to the development of CPAM. This study aims to investigate the expression profile and analyze intercellular communication networks to identify genes potentially associated with type II CPAM pathogenesis and therapeutic targets.MethodsRNA sequencing (RNA-seq) was performed on samples extracted from both the cystic area and the adjacent normal tissue post-surgery in CPAM patients. Iterative weighted gene correlation network analysis (iWGCNA) was used to identify genes specifically expressed in type II CPAM. Single-cell RNA-seq (scRNA-seq) was integrated to unveil the heterogeneity in cell populations and analyze the communication and interaction within epithelial cell sub-populations.ResultsA total of 2,618 differentially expressed genes were identified, primarily enriched in cilium-related biological process and inflammatory response process. Key genes such as EDN1, GPR17, FPR2, and CHRM1, involved in the G protein-coupled receptor (GPCR) signaling pathway and playing roles in cell differentiation, apoptosis, calcium homeostasis, and the immune response, were highlighted based on the protein-protein interaction network. Type II CPAM-associated modules, including ciliary function-related genes, were identified using iWGCNA. By integrating scRNA-seq data, AGR3 (related to calcium homeostasis) and SLC11A1 (immune related) were identified as the only two differently expressed genes in epithelial cells of CPAM. Cell communication analysis revealed that alveolar type 1 (AT1) and alveolar type 2 (AT2) cells were the predominant communication cells for outgoing and incoming signals in epithelial cells. The ligands and receptors between epithelial cell subtypes included COLLAGEN genes enriched in PI3K-AKT singaling and involved in epithelial to mesenchymal transition.ConclusionsIn summary, by integrating bulk RNA-seq data of type II CPAM with scRNA-seq data, the gene expression profile and critical signaling pathways such as GPCR signaling and PI3K-AKT signaling pathways were revealed. Abnormally expressed genes in these pathways may disrupt epithelial-mesenchymal transition and contribute to the development of CPAM. Given the effectiveness of prenatal treatments of microcystic CPAM using maternal steroids and maternal betamethasone administration, targeting the genes and signaling pathways involved in the development of CPAM presents a promising therapeutic strategy.

The downregulation of genes encoding muscle proteins have a potential role in the development of scrotal hernia in pigs.

Testicular descent is a physiological process regulated by many factors. Eventually, disturbances in the embryological/fetal development path facilitate the occurrence of scrotal hernia, a congenital malformation characterized by the presence of intestinal portions within the scrotal sac due to the abnormal expansion of the inguinal ring. In pigs, some genes have been related to this anomaly, but the genetic mechanisms involved remain unclear. This study aimed to investigate the expression profile of a set of genes potentially involved with the manifestation of scrotal hernia in the inguinal ring tissue. Tissue samples from the inguinal ring/canal of normal and scrotal hernia-affected male pigs with approximately 30 days of age were used. Relative expression analysis was performed using qPCR to confirm the expression profile of 17 candidate genes previously identified in an RNA-Seq study. Among them, the Myosin heavy chain 1 (MYH1), Desmin (DES), and Troponin 1 (TNNI1) genes were differentially expressed between groups and had reduced levels of expression in the affected animals. These genes encode proteins involved in the formation of muscle tissue, which seems to be important for increasing the resistance of the inguinal ring to the abdominal pressure, which is essential to avoid the occurrence of scrotal hernia. The downregulation of muscular candidate genes in the inguinal tissue clarifies the genetic mechanisms involved with this anomaly in its primary site, providing useful information for developing strategies to control this malformation in pigs and other mammals.

Immunotherapy in the Context of Aortic Valve Diseases.

Aortic valve disease (AVD) affects millions of people around the world, with no pharmacological intervention available. Widely considered a multi-faceted disease comprising both regurgitative pathogenesis, in which retrograde blood flows back through to the left ventricle, and aortic valve stenosis, which is characterized by the thickening, fibrosis, and subsequent mineralization of the aortic valve leaflets, limiting the anterograde flow through the valve, surgical intervention is still the main treatment, which incurs considerable risk to the patient. Though originally thought of as a passive degeneration of the valve or a congenital malformation that has occurred before birth, the paradigm of AVD is shifting, and research into the inflammatory drivers of valve disease as a potential mechanism to modulate the pathobiology of this life-limiting pathology is taking center stage. Following limited success in mainstay therapeutics such as statins and mineralisation inhibitors, immunomodulatory strategies are being developed. Immune cell therapy has begun to be adopted in the cancer field, in which T cells (chimeric antigen receptor (CAR) T cells) are isolated from the patient, programmed to attack the cancer, and then re-administered to the patient. Within cardiac research, a novel T cell-based therapeutic approach has been developed to target lipid nanoparticles responsible for increasing cardiac fibrosis in a failing heart. With clonally expanded T-cell populations recently identified within the diseased valve, their unique epitope presentation may serve to identify novel targets for the treatment of valve disease. Taken together, targeted T-cell therapy may hold promise as a therapeutic platform to target a multitude of diseases with an autoimmune aspect, and this review aims to frame this in the context of cardiovascular disease, delineating what is currently known in the field, both clinically and translationally.

The Rare Condition of a Double Cervix: Results from the High-Risk Human Papillomavirus-Based Cervical Cancer Screening Program in the Lazio Region.

Precancerous and cancerous lesions of the uterine cervix are known to be associated with Human Papillomavirus (HPV) infection. The screening of high-risk (HR)-HPV infection in the female population has led to the discovery of several cases of a double cervix, a congenital malformation that is very rare. The purpose of this study was to evaluate HR-HPV infections in women with a double cervix within the National Cervical Cancer Screening program of the Lazio region (Italy). From June 2021 to March 2024, a total of 142,437 samples were analyzed by Seegene's Anyplex TM II HR-HPV method, which identifies 14 HR-HPV genotypes. For each woman identified with a double cervix, two separate samples were taken from both cervices and analyzed separately. Twenty-seven women with a double cervix were identified (0.019%): 23 women were tested as negative for both cervices, while the remaining four (namely A, B, C, and D) resulted positive. By genotyping, the following results were obtained: (A) Both samples showed genotype 31; (B) one cervix was negative while the other showed genotype 58; (C) one cervix was positive for HPV 18 and 31 while for 18, 31, and 33 in the other; and (D) one cervix showed genotype 66 while the other carried the 66 and 68 genotypes. Double cervix is a very rare condition where the presence of HR-HPV genotypes is not homogeneous. As already described, our study confirms that different genotypes can be detected in double cervix malformation, suggesting the need to perform HPV screening on brushing samples from both cervices.