Homozygous Null TBX4 Mutations Lead to Posterior Amelia with Pelvic and Pulmonary Hypoplasia.

The development of hindlimbs in tetrapod species relies specifically on the transcription factor TBX4. In humans, heterozygous loss-of-function TBX4 mutations cause dominant small patella syndrome (SPS) due to haploinsufficiency. Here, we characterize a striking clinical entity in four fetuses with complete posterior amelia with pelvis and pulmonary hypoplasia (PAPPA). Through exome sequencing, we find that PAPPA syndrome is caused by homozygous TBX4 inactivating mutations during embryogenesis in humans. In two consanguineous couples, we uncover distinct germline TBX4 coding mutations, p.Tyr113∗ and p.Tyr127Asn, that segregated with SPS in heterozygous parents and with posterior amelia with pelvis and pulmonary hypoplasia syndrome (PAPPAS) in one available homozygous fetus. A complete absence of TBX4 transcripts in this proband with biallelic p.Tyr113∗ stop-gain mutations revealed nonsense-mediated decay of the endogenous mRNA. CRISPR/Cas9-mediated TBX4 deletion in Xenopus embryos confirmed its restricted role during leg development. We conclude that SPS and PAPPAS are allelic diseases of TBX4 deficiency and that TBX4 is an essential transcription factor for organogenesis of the lungs, pelvis, and hindlimbs in humans.

Anesthetic management in an infant with tetra-amelia syndrome with congenital maxillomandibular fusion: A case report.

A 10-month-old girl who had tetra-amelia syndrome and congenital maxillomandibular fusion (syngnathia) was scheduled for the surgical fusion separation. Anesthetic management for this case was considerably challenging. Standard monitoring was still applied to the patient's extremities. IV access was suspected to be difficult but firmly needed before intubation to provide resuscitation during an emergency. Connecting anesthetic circuit with nasopharyngeal airway was the preferred technique due to its benefits such as maintaining spontaneous ventilation, providing inhaled anesthetic, as well as monitoring oxygenation and ventilation. Importantly, the cornerstones for handling such complicated cases are multidisciplinary approach and teamwork.

Presence of congenital anomalies in three dog litters.

This report describes multiple congenital malformations found in three dog litters delivered by emergency caesarean section. In all of the litters, some puppies were born alive but were euthanized because of the seriousness of their malformations and low probability of survival. In two litters, gastroschisis was associated with amelia of the right anterior limb. Other malformations such as anencephaly were also found in three puppies among the different litters. This report describes the morphological findings of the affected puppies, discusses the most appropriate terminologies for each case and highlights the importance of an epidemiological survey to identify potential factors associated with the cases.

Isolated Bilateral Upper Limb Amelia - A Rare Case Report.

Introduction: Congenital upper limb amelia is one of the extremely rare conditions. It is defined as a complete absence of upper limbs. It may present as isolated or with other associated anomalies. Case Report: We present a case of a 2-year-old male child with congenital complete absence of bilateral upper limb. This male child was born after four female children. With the advancement in modern-era prenatal diagnostic facilities and a better understanding of fetal-maternal drug pharmacology, such cases are rare entity. Conclusion: Amelia is a very rare and challenging situation for clinicians. Regular prenatal checkup and knowledge of maternal and fetal drug interactions during pregnancy are key factors for prevention.

Limb-body wall complex: Literature review and case report.

INTRODUCTION: Body wall anomalies comprise a wide range of malformations. Limb-Body wall complex (LBWC) represents the most severe presentation of this group, with life threatening malformations in practically all the cases, including craniofacial, body wall defects, and limb anomalies. There is no consensus about its etiology and folding and gastrulation defects have been involved. Also, impaired angiogenesis has been proposed as a causative process. CASE REPORT: We present the case of a masculine stillborn, product of the first pregnancy in a 15-year-old, apparently healthy mother. He was delivered at 31 weeks of gestation due to an early rupture of membranes. He presented with multiple malformations including a wide body wall defect with multiple organ herniation and meromelia of the lower right limb. DISCUSSION AND CONCLUSIONS: LBWC represents a severe and invariably fatal pathology. There are no described risk factors, nevertheless, this case presented in a teenage mother, a well-described risk factor for other body wall anomalies. Its diagnosis allows us to discriminate between other pathologies that require prenatal or postnatal specialized treatment.

Application of Biostimulant in Seeds and Soil on Three Chickpea Varieties: Impacts on Germination, Vegetative Development, and Bacterial Facilitation of Nitrogen and Phosphorus.

Chickpeas (Cicer arietinum L.) are a valuable legume crop due to their nutritional value. To maintain chickpea productivity and avoid the adverse effects of climate change on soil and plant processes, it is crucial to address demand. Achieving this necessitates implementing sustainable agricultural practices incorporating the use of biostimulants, adaptable crops for arid conditions, as well as pest and disease-resistant crops that are sustainable over time. Three varieties of chickpeas were analysed to determine the effect of two different biostimulant application methods on both germination and vegetative growth. Possible effects due to location were also examined by conducting tests at two different sites. Significant variations in biostimulant response were evident only during the germination period, but not during the vegetative development stage, where the observed statistical differences were influenced more by the location or variety of chickpeas employed. Furthermore, this study examined the effect of biostimulants on nutrient cycling within the soil-plant microbiota system. Nitrogen-fixing bacteria (NFB) are present in the soil of chickpea crops at an order of magnitude of 107 CFU/g DS. Additionally, an average concentration of 106 CFU/g DS of phosphorus-mobilising bacteria was observed. Applying biostimulants (BioE) to seeds resulted in a successful germination percentage (GP) for both Amelia (AM) and IMIDRA 10 (IM) varieties.

Case report: vertebral body tethering for idiopathic scoliosis in a patient with bilateral phocomelia.

PURPOSE: The purpose of this study is to present a case report of a patient with bilateral upper extremity phocomelia with progressive scoliosis, who underwent vertebral body tethering (VBT). METHODS: This is a case report on the use of VBT in a patient with scoliosis and bilateral congenital phocomelia, with 5 year follow-up. RESULTS: A male patient with bilateral phocomelia had early onset scoliosis that progressed to 45° at age 10. Surgical options were discussed, including traditional VBT, posterior spinal fusion, growing rods, magnetically controlled growing rods, and vertical expandible prosthetic titanium ribs. These options would limit the flexibility of the spine. Given these pitfalls, VBT was chosen, as it would address the scoliosis while maintaining trunk flexibility. Preoperatively, he had 45° right main thoracic curve, bending to 22°; he was Risser 0 with open triradiate cartilage. He underwent T6-T11 thoracoscopic VBT, with postoperative correction to 37°. Postoperatively, the patient was able to continue to use his lower extremities for writing, feeding, and personal grooming. He had no postoperative complications. At 3 years, his curve was 21°, and at 5 years was 19°. CONCLUSION: This case describes a novel technique for treating scoliosis in patients with bilateral phocomelia. Other forms of scoliosis surgical treatment limit motion of the spine. Due to this, we present VBT as an option for this unique set of patients for correcting scoliosis, while also preserving trunk flexibility for its role in feeding and self-care.

Helping to shine light on the Dark Ages: Applying the bioarchaeology of care approach to remains from the early Anglo-Saxon cemetery at Worthy Park.

OBJECTIVE: To test the hypothesis that a bioarchaeological focus on health-related care provision can contribute to the currently limited understanding of social practice in Early Anglo-Saxon England (mid5th-early7th centuries AD). MATERIALS: Published descriptions of pathology in 69 adult remains from the Early Anglo-Saxon cemetery of Worthy Park, southern England. METHODS: Three case studies (one examining likely need for care at an individual level and two at a population level) were undertaken using the bioarchaeology of care approach. RESULTS: Analyses indicate likely care provision ('direct support' and/or 'accommodation of difference') to Worthy Park individuals experiencing temporary or permanent disability. Interpretation suggests community interdependence, cooperation, flexibility and tolerance of difference, as well as cultural and socioeconomic mechanisms for managing physical and social challenges of ageing. CONCLUSIONS: This study provides proof of concept that bioarchaeology of care analysis can offer new insights into social practice in this period. SIGNIFICANCE: This study demonstrates that a bioarchaeological focus on caregiving behaviours in an Early Anglo-Saxon community extends modern thinking about social relations in post-Roman Britain, offering a model for future investigations into social practice in this, and potentially other, periods. More generally, it illustrates the richness of results achievable when combining bioarchaeological and historical research. LIMITATIONS: Reliance on secondary sources limited detail (and potentially accuracy) of interpretation possible. SUGGESTIONS FOR FURTHER RESEARCH: This study's approach should be further tested and refined, either through application to different Anglo-Saxon (or other historic) populations or in a more thorough analysis of the Worthy Park sample itself.

Fetal Amelia With Hypoplastic Tibia and Terminal Fibular Hemimelia: A Case Report With Review of the Literature.

Congenital limb deformities, with a birth frequency of 0.55 per 1,000, are extremely rare prenatal defects that can present with either partial or complete lack of a limb or a specific portion of a limb. Amelia is a sporadic anomaly that is defined by the complete absence of a limb's skeletal elements, whereas hypomelia is defined by the incomplete development of a limb's skeletal elements. We present the case of a neonate with gross facial deformities in the form of the absence of both external ears and a saddle-shaped nose. The absence of the right lower limb bud was seen. The left lower limb was underdeveloped, noted only up to the thigh region with the hypoplastic distal part of the leg and absent foot. Genitals and the anus were absent. To the best of our knowledge, this case is exceptional in that congenital limb abnormalities are present at birth along with accompanying genital underdevelopment.

A combined case of amelia and phocomelia in a neonate, at JFK Maternity Center, Liberia.

We report a case of spontaneous rare birth deformity. A case of Amelia and Phocomelia in a neonate. Amelia is a rare congenital disorder, even more so, is the combined amelia and phocomelia in a neonate. True Phocomelia was defined as the total absence of the intermediate segments of the limb. With the hand or foot (normal, almost normal, or malformed), directly attached to the trunk. The common aetiological association with phocomelia is from the use of thalidomide and genetic inheritance, as an autosomal recessive trait, involving chromosome 8. Isolated amelia is not generally considered to be of genetic origin. We present a neonate delivered by a 28-years multipara in Liberia, in West Africa Sub-Region, with amelia involving the two upper limbs, right lower limb and a Phocomelia involving the left lower limb (absence of tibia and fibula and feet with three toes). Africa is the only continent not included in the International Clearinghouse for Birth Defects Surveillance and Research. It is hoped that case reports of congenital limb deformities from Africa, will contribute to the formation of a database for birth defects shortly. Funding: None declared.

Motor Imagery Training of Reaching-to-Grasp Movement Supplemented by a Virtual Environment in an Individual With Congenital Bilateral Transverse Upper-Limb Deficiency.

This study explored the effect of kinesthetic motor imagery training on reaching-to-grasp movement supplemented by a virtual environment in a patient with congenital bilateral transverse upper-limb deficiency. Based on a theoretical assumption, it is possible to conduct such training in this patient. The aim of this study was to evaluate whether cortical activity related to motor imagery of reaching and motor imagery of grasping of the right upper limb was changed by computer-aided imagery training (CAIT) in a patient who was born without upper limbs compared to a healthy control subject, as characterized by multi-channel electroencephalography (EEG) signals recorded before and 4, 8, and 12 weeks after CAIT. The main task during CAIT was to kinesthetically imagine the execution of reaching-to-grasp movements without any muscle activation, supplemented by computer visualization of movements provided by a special headset. Our experiment showed that CAIT can be conducted in the patient with higher vividness of imagery for reaching than grasping tasks. Our results confirm that CAIT can change brain activation patterns in areas related to motor planning and the execution of reaching and grasping movements, and that the effect was more pronounced in the patient than in the healthy control subject. The results show that CAIT has a different effect on the cortical activity related to the motor imagery of a reaching task than on the cortical activity related to the motor imagery of a grasping task. The change observed in the activation patterns could indicate CAIT-induced neuroplasticity, which could potentially be useful in rehabilitation or brain-computer interface purposes for such patients, especially before and after transplantation. This study was part of a registered experiment (ID: NCT04048083).

First Trimester Diagnosis of Body Stalk Anomaly Confirmed Postnatally.

Body stalk anomaly, with a prevalence of 0.12 in 10,000 births, occurs when abdominal organs develop outside the abdominal cavity while remaining attached to the placenta in the fetus. This article relates to a rare case of body stalk anomaly detected in the first trimester of pregnancy. The images presented are characteristic to the anomaly. A postnatal evaluation confirmed the findings and helped in comprehensive counseling of the patient.

Functional outcomes in bilateral upper limb Amelia patient with scoliosis post vertical expandable prosthetic titanium rib (VEPTR) application: A case report.

INTRODUCTION: Congenital upper limb Amelia is one of the extremely rare conditions in the world. Defined as complete absence of a limb which may present as isolated defect or as a part of syndrome with associated anomalies. PRESENTATION OF THE CASE: We report a case of a medically free 6-year-old boy with bilateral upper limb Amelia associated with right thoracolumbar idiopathic Scoliosis. DISCUSSION: Treatment for early onset scoliosis includes either posterior spinal fusion and instrumentation, or Vertical Expandable Prosthetic Titanium Rib (VEPTR). The choice of care for our patient was decided to be VEPTR alone as definitive management. Up to our knowledge, there are very scanty articles published regarding treatment for such cases. CONCLUSION: Patient underwent vertical expandable prosthetic titanium rib (VEPTR) application for his large 45-degree curve as a definitive treatment and still have his preoperative physical functions, in terms of using lower limbs in daily living activities.

Limb body wall complex: Its delineation and relationship with amniotic bands using clustering methods.

BACKGROUND: Despite the numerous reports on the limb body wall complex (LBWC), this association has never been adequately defined. Amniotic bands (AB) are frequently present but their role remains unclear. Since most reports were based on clinical and often subjective diagnoses, the aim of this work was to define LBWC and the role of AB, minimizing subjectivity. METHODS: Data were obtained from the ECLAMC maternity hospitals network database. A total of 450 live and stillborn infants, born during 1967-2013, with AB or the LBWC were selected. A hierarchical cluster analysis was used to classify cases into homogeneous groups (sharing similar associated defects); robustness of the classification was confirmed with a discriminant analysis. The frequency of associated defects was compared among groups; those whose frequency differed significantly were included in a logistic regression to establish their association within each group. RESULTS: The cluster analysis identified two groups: a body wall defect (BWD) predominating in one, AB in the other. These groups were further divided into: BWD (cases with only BWD), AB (with only AB), BWD + AB, and NONE (with neither). Association with caudal defects and lower limb amelia was observed for BWD, with cephalic defects and upper limb amputations for BWD + AB. CONCLUSIONS: The results, obtained with the least possible subjectivity, indicated that BWD and BWD + AB are different conditions. Since BWD specifically associates with amelia, we propose that this defect and not any limb deficiency should be considered as inclusion criterium and that it should be included in the BWD acronym as LBWC.

Identification of a putative man-made object from an underwater crash site using CAD model superimposition.

In order to identify an object in video, a comparison with an exemplar object is typically needed. In this paper, we discuss the methodology used to identify an object detected in underwater video that was recorded during an investigation into Amelia Earhart's purported crash site. A computer aided design (CAD) model of the suspected aircraft component was created based on measurements made from orthogonally rectified images of a reference aircraft, and validated against historical photographs of the subject aircraft prior to the crash. The CAD model was then superimposed on the underwater video, and specific features on the object were geometrically compared between the CAD model and the video. This geometrical comparison was used to assess the goodness of fit between the purported object and the object identified in the underwater video.

Representation of Multiple Body Parts in the Missing-Hand Territory of Congenital One-Handers.

Individuals born without one hand (congenital one-handers) provide a unique model for understanding the relationship between focal reorganization in the sensorimotor cortex and everyday behavior. We previously reported that the missing hand's territory of one-handers becomes utilized by its cortical neighbor (residual arm representation), depending on residual arm usage in daily life to substitute for the missing hand's function [1, 2]. However, the repertoire of compensatory behaviors may involve utilization of other body parts that do not cortically neighbor the hand territory. Accordingly, the pattern of brain reorganization may be more extensive [3]. Here we studied unconstrained compensatory strategies under ecological conditions in one-handers, as well as changes in activation, connectivity, and neurochemical profile in their missing hand's cortical territory. We found that compensatory behaviors in one-handers involved multiple body parts (residual arm, lips, and feet). This diversified compensatory profile was associated with large-scale cortical reorganization, regardless of cortical proximity to the hand territory. Representations of those body parts used to substitute hand function all mapped onto the cortical territory of the missing hand, as evidenced by task-based and resting-state fMRI. The missing-hand territory also exhibited reduced GABA levels, suggesting a reduction in connectional selectivity to enable the expression of diverse cortical inputs. Because the same body parts used for compensatory purposes are those showing increased representation in the missing hand's territory, we suggest that the typical hand territory may not necessarily represent the hand per se, but rather any other body part that shares the functionality of the missing hand [4].

O declínio da luta pelo direito à saúde e a necessária repolitização da Reforma Sanitária Brasileira na escrita de Amélia Cohn / The decline in the fight for the right to health and the necessary repoliticization of the Brazilian Health Reform in Amélia Cohn's writing

Resumo A garantia do direito à saúde no Brasil tem sido bastante discutida nos últimos anos, entretanto, esse é um debate antigo, ao qual este artigo busca resgatar. O objetivo deste estudo é apresentar as contribuições da socióloga Amélia Cohn referentes à Reforma Sanitária Brasileira (RSB), para discutir a atualidade de suas questões e refletir sobre a relação entre saúde e democracia. As teses de Cohn sobre a RSB são discutidas com base nos textos de sua autoria, publicados entre 1989 e 2013. A partir da ideia de "declínio do campo da RSB", buscou-se sistematizar o conjunto das suas críticas nos diferentes períodos históricos. Enfatiza-se que, já em 1992, a autora afirmou o esgotamento da RSB. No contexto de implantação do SUS na década de 1990, apontou a necessidade de elaboração de um novo projeto de saúde para o país. Na década seguinte, Cohn reconheceu a perda do protagonismo na saúde devido à despolitização do campo da RSB no processo de implantação do SUS, o que fragilizou a distinção entre as novas formas de acumulação de capital - a incorporação da racionalidade de mercado na produção e a oferta de serviços e a garantia do direito à saúde.

Abstract The guarantee of the right to health in Brazil has been widely discussed in recent years; however, this is an old debate, to which this article seeks to contribute. This study aims to show the contributions of the sociologist Amélia Cohn regarding the Brazilian Sanitary Reform (BSR), to discuss how current are her questions and reflect on the relationship between health and democracy. Cohn`s theses on BSR are discussed based on her texts, published between 1989 and 2013. Based on the idea of "decline on the field of BSR," we sought to systematize the set of her critical thinking in the different historical periods. Note that, already in 1992, the author affirmed the exhaustion of the BSR. In the context of the implementation of Brazilian National Health System (SUS) in the 1990s, the author pointed out the need to develop a new health project for the country. In the following decade, Cohn's recognized the loss of protagonism in the health field due to the depoliticization of the BSR in the implantation process of SUS, which weakened the distinction between the new forms of capital accumulation - the incorporation of market rationality in the production and supply of services - and the guarantee of the right to health.

Multiple imputation for time series data with Amelia package.

Time series data are common in medical researches. Many laboratory variables or study endpoints could be measured repeatedly over time. Multiple imputation (MI) without considering time trend of a variable may cause it to be unreliable. The article illustrates how to perform MI by using Amelia package in a clinical scenario. Amelia package is powerful in that it allows for MI for time series data. External information on the variable of interest can also be incorporated by using prior or bound argument. Such information may be based on previous published observations, academic consensus, and personal experience. Diagnostics of imputation model can be performed by examining the distributions of imputed and observed values, or by using over-imputation technique.

Omphalocele major with absent lower limb.

A newborn delivered by Caesarian section presented with an absent anterior abdominal wall and visible bowel loops and liver. The defect was covered by a thin membrane. The patient had associated absent left lower limb and right foot fusion defect. The patient was haemodynamically stable; general condition was average. No genito-urinary abnormality was detected. The anal opening was present normally, and the patient passed meconium immediately after birth. A diagnosis of omphalocele major with amelia was made. The patient was initially managed by topical application of povidone-iodine for eschar formation and epithelisation of the sac. The patient was discharged after 1 week with advice for regular follow-up.