Treatment Of Congenital Defects Research Articles

Application of convolutional neural networks for the classification of metaphase chromosomes

To train a deep convolutional neural networks (CNN) using a labeled data set to classify the metaphase chromosomes and test its accuracy for chromosomal identification. Three thousand and three hundred individuals undergoing surveillance for chromosomal disorders at the Laboratory for Comprehensive Prevention and Treatment of Birth Defects, Ningbo Maternal and Child Health Care Hospital from January 2013 to July 2019 were enrolled. A total of 3 300×46 chromosome images were included, of which 70% were used as the training set and 30% were used as the test set for the deep CNN. The accuracy of chromosome counting and "cutting + recognition + arrangement + automatic analysis" of the model were respectively evaluated. Another 80 images were collected to record the time and accuracy of chromosome classification by geneticists and the model, respectively, so as to assess the practical value of the model. The CNN model was used to count the chromosomes with an accuracy of 61.81%, and the "cutting + recognition + arrangement + automatic analysis" accuracy of the model was 96.16%. Compared with manual operation, the classification time of the CNN model has been greatly reduced, and its karyotyping accuracy was only 3.58% lower than that of geneticists. The CNN model has a high performance for chromosome classification and can significantly reduce the work load involved with the segmentation and classification and improve the efficiency of chromosomal karyotyping, thereby has a broad application prospect.

The global challenges of surgical congenital anomalies: Evidence, models, and lessons

The treatment of congenital anomalies (structural birth defects) is common to all the surgical sub-specialties dealing with children. Globally more than 90 % of all babies born with a congenital anomaly are born in middle-and-low-income countries where there is often limited access to needed surgical care. Challenges include lacks of early identification, registry and surveillance systems, missing referral pathways, shortage of trained surgical expertise and insufficient surgical infrastructure. Poverty, transportation logistics, financial constraints and social stigma are also serious barriers for families. There is, however, growing recognition of the priority to expand services, encouraged by the World Health Organization and other global players, and examples of successful models of care. Registry programs are growing, especially in Latin America. The Ponseti method of clubfoot care has been revolutionary on a global scale. The role of not-for-profit non-governmental-organizations has been instrumental in fundraising, training and logistical support as exemplified in the care of oro-facial clefts. Specialized “niche” hospitals are providing needed sub-specialist expertise. The way forward includes the need for effective partnerships, innovative methods to distribute care out from referral hospitals into the districts and the development of national plans embedded in national health policy.

Compression-distraction devices in the treatment of congenital disorders in children. Case series

Relevance. In many cases, Pierre Robin sequence and congenital micrognathia lead to respiratory failure, obstructive sleep apnea, and aspiration of food due to swallowing problems. Compression-distraction osteogenesis method allowed for the effective achievement of a stable clinical result with the minimum losses for the child's body.Purpose. The study aimed to conduct a retrospective analysis of various types of compression-distraction devices based on the Department of Maxillofacial Surgery of the Republican Children's Clinical Hospital.Material and Methods. Since 2010, 36 children aged three months to 13 years have been operated, 20 boys and 16 girls. Four children were operated using an multi-vector external compression-distraction device. Two children with Pierre Robin sequence had surgery with a Conmet intraoral compression-distraction device, 27 children – with a KLS Martin bone-borne compression-distraction device, of which 15 had Pierre Robin sequence, and 12 had congenital lower micrognathia. Seven children had tracheostomy, which had been placed due to permanent sleep apnea.Results. Three (8.33%) children were operated using external compression-distraction devices. From three months to one year. A patient with Pierre Robin sequence, tracheostomy, and cannula. A tracheostomy was installed at the age of 15 days due to persistent apnea. At three months of age, bilateral osteotomy of the mandible with the installation of an external compression-distraction device was performed. Compression was for three days; then, they began distraction of one mm/day for 15 days. Five months later, the child began to breathe freely through the natural respiratory tract; under mask anesthesia, the compression-distraction device was removed. Four children (11.11%) aged 8 to 12 months were operated using multi-vector external compression-distraction device. A patient aged one year with Pierre Robin sequence, tracheostomy, and cannula. The external compression-distraction device was installed at the age of eight months. The distraction period was 12 days. The consolidation period was three months. The treatment result was independent breathing through the natural respiratory tract. The tracheostomy cannula was removed. Twenty-nine children 2 (5.56%) were operated using intraoral bone-borne compressiondistraction devices. A child aged 14 months, diagnosed with Pierre Robin sequence, complained of periodic sleep apnea with signs of acrocyanosis. Moderate to severe obstructive sleep apnea was detected. A bilateral osteotomy of the mandible was performed, and a bone-borne compression-distraction device was installed. Compression was for three days, then the distraction of 0.5 mm twice a day – for 14 days. Distraction was performed at 14 mm. After five months, the bone-borne CDD was removed, and polysomnography was repeated. The apnea-hypopnea index (AHI) was <5. Respiratory function was fully restored.Conclusion. Thus, 24 children showed successful results with the use of compression-distraction device (an orthognathic occlusion was formed, glossoptosis was eliminated, natural breathing and feeding were restored); 11 children did not have a satisfactory result (due to distraction interruption, it was not possible to achieve a physiological bite, there was postoperative wound suppuration with wound dehiscence). There was one negative result due to trauma: the child fell on his chin at home during the consolidation period, and the compression-distraction device broke, which resulted in disocclusion.

Biallelic variants in KCTD19 associated with male factor infertility and oligoasthenoteratozoospermia.

Can whole-exome sequencing (WES) reveal new genetic factors responsible for male infertility characterized by oligozoospermia? We identified biallelic missense variants in the Potassium Channel Tetramerization Domain Containing 19 gene (KCTD19) and confirmed it to be a novel pathogenic gene for male infertility. KCTD19 is a key transcriptional regulator that plays an indispensable role in male fertility by regulating meiotic progression. Kctd19 gene-disrupted male mice exhibit infertility due to meiotic arrest. We recruited a cohort of 536 individuals with idiopathic oligozoospermia from 2014 to 2022 and focused on five infertile males from three unrelated families. Semen analysis data and ICSI outcomes were collected. WES and homozygosity mapping were performed to identify potential pathogenic variants. The pathogenicity of the identified variants was investigated in silico and in vitro. Male patients diagnosed with primary infertility were recruited from the Reproductive and Genetic Hospital of CITIC-Xiangya. Genomic DNA extracted from affected individuals was used for WES and Sanger sequencing. Sperm phenotype, sperm nuclear maturity, chromosome aneuploidy, and sperm ultrastructure were assessed using hematoxylin and eosin staining and toluidine blue staining, FISH and transmission electron microscopy. The functional effects of the identified variants in HEK293T cells were investigated via western blotting and immunofluorescence. We identified three homozygous missense variants (NM_001100915, c.G628A:p.E210K, c.C893T:p.P298L, and c.G2309A:p.G770D) in KCTD19 in five infertile males from three unrelated families. Abnormal morphology of the sperm heads with immature nuclei and/or nuclear aneuploidy were frequently observed in individuals with biallelic KCTD19 variants, and ICSI was unable to rescue these deficiencies. These variants reduced the abundance of KCTD19 due to increased ubiquitination and impaired its nuclear colocalization with its functional partner, zinc finger protein 541 (ZFP541), in HEK293T cells. The exact pathogenic mechanism remains unclear, and warrants further studies using knock-in mice that mimic the missense mutations found in individuals with biallelic KCTD19 variants. Our study is the first to report a likely causal relationship between KCTD19 deficiency and male infertility, confirming the critical role of KCTD19 in human reproduction. Additionally, this study provided evidence for the poor ICSI clinical outcomes in individuals with biallelic KCTD19 variants, which may guide clinical treatment strategies. This work was supported by the National Key Research and Developmental Program of China (2022YFC2702604 to Y.-Q.T.), the National Natural Science Foundation of China (81971447 and 82171608 to Y.-Q.T., 82101961 to C.T.), a key grant from the Prevention and Treatment of Birth Defects from Hunan Province (2019SK1012 to Y.-Q.T.), a Hunan Provincial Grant for Innovative Province Construction (2019SK4012), and the China Postdoctoral Science Foundation (2022M721124 to W.W.). The authors declare no conflicts of interest. N/A.

The effectiveness of graphic prediction of the shape of the dental arches of the milk bite in the treatment of congenital anomalies

Currently, experts have noted the need to search for new research methods based on the selection of the most stable anatomical landmarks for the graphic construction of dental arches of the milk bite and the assessment of their effectiveness in clinical practice. A retrospective biometric study of 27 pairs of plaster models of mammary bite jaws with their optimal functional occlusive relationships was carried out to develop diagnostic methods. Orthodontic treatment of 15 children with congenital pathology of the maxillofacial region was carried out by fixed arc equipment. Based on the analysis of biometrics, methods for the graphic construction of dental arches were developed. The first method was based on the laws of circle geometry (the prototype of the A.M. Schwarz method) and the calculation of the radius of the circle along its length (L = 2R). To the sum of the crowns of 10 milk teeth, the value of the diastem component (in our case, 9 mm) was added and the length of the semicircle was obtained, which was enough to divide by the number and get the magnitude of the radius of the circle. The effectiveness of treatment of children with unilateral cleft lip and alveolar process is shown. Analysis of dental arch biometric data showed that on the side of the cleft, the distance from the conditional sagittal to the milk canine was (11.52 0.93) mm before treatment, and after treatment, the studied parameter was (16.39 0.64) mm (p ˂ 0.05). On the cotrlateral side, the difference in the change in the position of the canine was not significant and in the dynamics of treatment changed from (14.93 0.79) mm to (16.27 0.84) mm (p ˃ 0.05). The diagonals of the dental arches (central-molar) on both sides after treatment were (35.52 1.13) mm. Thus, taking into account the data obtained, it was concluded that the graphic reproduction of the dental arch of the milk bite in the treatment of children with anomalies of the dental arches was made.

Year-end academic review of 2021: Advances in the field of birth defect prevention and control in China as of 2021

Year-end academic review of 2021: Advances in the field of birth defect prevention and control in China as of 2021

Prevalence of fetal and neonatal mortality due to congenital anomalies in the state of Maranhão, Brazil, from 2001–2016

Introduction: The infant mortality rate (IMR) is an important health indicator directly associated with living conditions, prenatal care coverage, social development conditions, and parental education, among others. Worldwide, the infant mortality rate was 29/1000 live births in 2017. Therefore, this study aimed to evaluate the fetal and infant mortality rates due to congenital anomalies (CA) in Maranhao from 2001 to 2016. Methods: Data were obtained from the SINASC, and SIM databases. We used simple linear regression, Poisson distribution, and ANOVA (Bonferroni’s post hoc test). We analyzed the public data (2001–2016) of 1934858 births and determined the fetal, neonatal, perinatal, and post-neonatal mortality rates associated with CA by mesoregions. Results: The IMR in Maranhao was 17.01/1000 live births (95%CI, 13.30-20.72) and CA was the cause of death in 13.3% of these deaths. Mortality due to CA (per 1000 live births) was 0.76 (95%CI, 0.74–0.85) for fetal mortality rate and 2.27 (95%CI, 1.45-3.10) for infant mortality rate. Geographic and temporal variations were observed with a slight increase in recent years for deaths attributable to CA, and in the northern part of Maranhao. Conclusions: Mortality rates due to CA in Maranhao increased over the period 2001–2016 possibly as a result of improved maternal-infant health conditions eliminating other causes of death. Therefore, efforts to improve early diagnosis and better treatment of congenital anomalies should be considered to reduce its impact on child mortality.

Free Vascularized Fibular Graft

Background: Free Vascularized Fibular Grafts (FVFGs) are currently a mainstay for extreme case reconstruction mainly due to their anatomical characteristics, reliability, and versatility in managing all bone defects cases. Method: This paper is a review article of the journal found by the author suitable for our reference in search engines with the keywords "Free Vascularized Fibular Graft" "surgery" "postoperative" and "complications". Results: FVFG can be used as management of bone defects such as post-trauma, infection or tumor, treatment of congenital abnormalities, avascular necrosis (AVN), arthrodesis, and pediatric pathology. Position Placement, Intercalary Resection, Bone Tumor Resection, Fibula Flap Retrieval, Allograft Preparation, Reconstruction at Recipient Site, and Intra-articular Resection need to be considered in the surgical procedure. Postoperative Monitoring in the ICU is necessary to evaluate Vital signs, flap viability, axle well as complications in patients. Conclusion: FVFG is a choice of bone defect reconstruction techniques with good results to be considered by orthopedic surgeons. Keywords: Free Vascularized Fibular Grafts, FVFG, Surgery post-operative, complication.

MODERN APPROACHES FOR THE DIAGNOSTICS AND TREATMENT OF NEWBORNS WITH ANORECTAL ATRESIAS (LITERARY DATA AND OWN EXPERIENCE)

Summary. The article is devoted to the problem of anorectal atresias in newborns, which are widespread and ranked first among the causes of disability in children. Based on the results of literature and our own experience, modern approaches to the diagnosis and treatment of congenital anomalies in newborns are presented. The 37 article presents epidemiology, modern views on diagnostics and treatment of main pathology and its complications in newborns. The necessity of improvement and wide introduction of prenatal diagnostics of anorectal atresias as an effective non-invasive method of early diagnostics of pathology is substantiated. The necessity of introduction of a complex of preventive measures at dirth defects, support of modern medical strategies and application of technically advanced methods of correction of a defect are emphasized. Generalization of own experience and modern approaches to the diagnosis, treatment and prevention of birth defects in newborns will be of great theoretical and practical importance for pediatric surgeries who are engaged in the issues of early detection of congenital malformations and their treatment, and to facilitate the coordination of specialists' efforts in improving the effectiveness of prenatal diagnosis of congenital anomalies and reducing lethality

Proposed Federal Bill to Mandate Insurance Coverage for Children With Congenital Anomalies.

The Ensuring Lasting Smiles Act was reintroduced in United States Congress in March 2019. If enacted, the bill will substantially limit private insurers' ability to deny coverage for the medically necessary treatment of congenital anomalies, including cleft palate and craniofacial anomalies. Coverage denials are currently a barrier to care for these individuals, especially for patients residing in states lacking coverage mandates. The purpose of this article is to describe the issues underlying the proposed federal legislation and provide a policy discussion to better inform cleft and craniofacial providers about pending legislation relevant to their practice.

3D Laparoscopy in Neonates and Infants.

This study focuses on the successful application of three-dimensional (3D) laparoscopic surgeries in the treatment of congenital anomalies and acquired diseases in the young pediatric population. The purpose of this scientific work consists in highlighting the spectrum, indications, applicability, and effectiveness of 3D endosurgery in children. Our experience is based on 110 endosurgical procedures performed in neonates and infants in the 3D format between January 2014 and May 2015. Depending on the type of operations, all patients were divided into the following groups: (1) inguinal herniorrhaphy (IH)-63 patients; (2) Nissen fundoplication (NF)-22 patients; (3) pyeloureteral anastomosis (PUA)-15 patients; (4) nephrectomy (NE)-5 patients; and (5) ovarian cystectomy (OC)-5 patients. The patients of the first three groups were compared with babies who underwent standard laparoscopic surgery, performed in the two-dimensional (2D) format during the same time period. The groups were organized according to patient demographics, operative report, and postoperative parameters. The patients were similar in terms of demographics and other preoperative parameters. There were significant differences in mean operative time between 3D and 2D procedures in the groups of patients with hydronephrosis and gastroesophageal reflux, which used manipulation with internal sutures (NF-37.95 minutes versus 48.42 minutes, P = .014; PUA-61.31 minutes versus 78.75 minutes, P = .019), but not in group after IH (15.88 minutes versus 15.57 minutes, P = .681). Postoperative parameters such as length of hospital stay and the number of complications were equivalent between groups. In this study, we demonstrated the success of 3D laparoscopy in small babies with inguinal hernia, gastroesophageal reflux, hydronephrosis, ovarian cyst, and multicystic kidney. Laparoscopy in 3D format lessens the duration of complex procedures, which utilize the use of the suture technique into the abdominal cavity. The perception of depth and the presence of tactile feedback make 3D laparoscopic surgery more acceptable when compared to traditional laparoscopy.

What if the Environment is a Person? Lineages of Epigenetic Science in a Toxic China

Through an ethnographic portrayal of the research on and treatment of congenital disorders in China, in this article I suggest that epigenetic research has the potential not only to exaggerate maternal blame but also to deindividualize ideas of maternal and parental responsibility. When a pregnant woman and the generations that produced her are understood through epigenetic studies as the environmental contexts of another person, responsibility has the potential to be reimagined as existing in relations and configurations that move beyond individualized understandings of personhood. Moreover, I argue that epigenetic models of development and inheritance at work in toxicological studies in China, and in the postgenomic embrace of complexity more generally, strongly resonate with existing social scientific models of Chinese life. Toxicologists conducting epigenetic research in China today reconfigure preexisting models of transgenerational, biosocial relationality to reassert a sense of social, environmental, and intergenerational connectivity in a moment of increasing individualization and chemical toxicity.

Surgical treatment of congenital anomalies of the aortic arch : Long-term results

Congenital anomalies of the aortic arch gather a wide spectrum of malformations concerning the aortic arch or some of its branches and the pulmonary artery. These malformations are rare (1 in 1000 live births) and sometimes responsible of complete (vascular ring) or partial (vascular sling) encirclement of the oesophagus, trachea or bronchi. In cases of symptomatic airways obstruction or oesophagus compression the surgical treatment is mandatory and curative. In this paper we describe the experience of Children's Hospital of Toulouse on the surgical treatment of congenital anomalies of aortic arch.

Congenital anomalies in Primorsky region.

Congenital anomalies in Primorsky region.

Birth Defect: An Over view

Birth defects are a leading cause of infant death, accounting for more than 1 of every 5 infant deaths. Every year more than 8.14 million children are born with a serious birth defect, due to genetic or environmental causes. In the low and middle income countries the burden of birth defects is much higher than in highincome countries. Birth defects may be due to chromosomal, single-gene or multifactorial causes. Environmental factors are responsible for 5–10% of total birth defects, and include nutritional deficiencies, infectious diseases, maternal medical conditions, teratogenic medications, alcohol, recreational drugs, and teratogenic pollutants. Birth defects can be diagnosed during pregnancy or after the baby is born, depending on the specific type of birth defect. Of course, many birth defects cannot be prevented; this is especially true of defects that have a genetic component. However, ultrasonography and maternal serum screening can be used to detect serious foetal anomalies, including neural tube defects and chromosomal disorders. Early detection and treatment of birth defects can help prevent stillbirth or physical and intellectual disabilities.J. Paediatr. Surg. Bangladesh 4(2): 58-66, 2013 (July)

Single-incision pediatric endosurgery in newborns and infants.

This study focuses on the successful application of single-incision pediatric endosurgery in the treatment of congenital anomalies and acquired diseases in neonates and infants. The purpose of this scientific review consists in highlighting the spectrum, indications, applicability, and effectiveness of single-port endosurgery in children during the first 3 postnatal months.

Addressing the public health challenge of birth defects in India

Birth defects consisted of a group of diverse clinical conditions categorized on the basis of a congenital presentation and a partly or wholly genetic etiology. Although individually rare, birth defects affect 2-3% of all births in India. As India has the largest global annual births, in absolute numbers, India may harbor the largest number of affected children worldwide. There is a need of strategic research and interventions to bring down the rate of birth defects and associated economic burden and also a need to actively screen and identifythem at early stage so necessary intervention (medical or surgical) could be initiated so as to reduce lifelong disability as a result of such defects. The recent child health screening and early intervention service initiative by the Government of India, the Rashtriya Bal Swasthya Karyakram under the National Health Mission is the first attempt in the direction toward providing services for some of the more prevalent birth defects and has the potential to alleviate suffering of affected children especially from rural areas. The data collected from this program could help policy makers to allocate sufficient funds aimed at treatment of birth defects and also develop behavior change communication strategies for prevention of the same.

Associated Risk Factors and Prevalence of Congenital Malformations in Ardabil, Iran

Introduction: Congenital anomalies are the most common cause of disability in developed and developing countries. Costs of hospitalization and treatment of congenital anomalies pose a significant burden to families and societies. The objective of the present study was to determine the associated risk factors and prevalence of congenital malformations in Ardabil, Iran. Methods: This cross-sectional study was conducted during November 2010 and July 2011 in three maternity hospitals, located in Ardabil, Iran. All live newborns were examined during the first 24 hours of life. Out of 6,868 live births during the study period, 57 neonates with congenital malformations were selected as the case group and 180 normal neonates were included as the control group. Data were collected using a researcher-made questionnaire and prenatal and delivery records. Data were entered to SPSS version 11, and statistical analysis was performed, using Chi-square along with univariate and multivariate logistic regressions. Results: The prevalence of congenital malformations was 8.2 per 1,000 live births. Musculoskeletal system malformation was the most common congenital abnormality (35.1%), followed by central nervous system disorders (22.8%), digestive system disorders (17.5%), urogenital system diseases (15.8%), and chromosomal anomalies (8.8%). Also, polyhydramnion (P=0.001, OR=14.4, CI:3.07-68.0), oligohydramnios (P=0.009, OR=13.09, CI:1.9-89.0), preeclampsia (P=0.000, OR=11.37, CI:2.99-43.14), unwanted pregnancy (P=0.000, OR=4.9, CI:2.0-13.0)), urinary tract infection in weeks 6-10 of pregnancy (P=0.045, OR=2.88, CI:1.0-18.11), and consanguinity (P=0.038, OR=2.23, CI:1.0-4.78) were determined as risk factors for congenital malformations. Conclusion:Early diagnostic survey of pregnant women with polyhydramnios, oligohydramnios, preeclampsia, unwanted pregnancy, urinary tract infection in weeks 6-10 of pregnancy, and consanguinity may be an appropriate solution toward the prevention of congenital anomalies.

Rhinoplasty

Congenital deficiencies of the alar cartilages are rare and often visible at birth but can occasionally present later. The authors review the anatomical development and discuss the incidence and treatment of congenital defects within the alar cartilages seen in rhinoplasty cases. The charts of 869 consecutive patients who underwent open rhinoplasty were retrospectively reviewed, and 8 cases of congenital defects of the alar cartilage within the middle crura were identified. Intraoperative photographs were taken of the alar deformities, and each patient underwent surgical correction. To simplify analysis, a classification of the defects was developed. A division was a cleft in the continuity of the alar cartilage with the 2 ends separate. A gap was a true absence of cartilage ranging from 1 to 4 mm, which can be accurately assessed in unilateral cases. A segmental loss was a defect greater than 4 mm. The 8 cases of deformity could be classified as 4 divisions, 3 gaps, and 1 segmental loss. None of the patients had a history of prior nasal trauma or nasal surgery. Six patients were women and 2 patients were men. In all cases, adequate projection and stability were achieved with a columellar strut. Asymmetry was minimized through concealer or tip grafts. There were no complications. Surgeons performing rhinoplasty surgery will encounter and should be prepared to deal with unexpected congenital defects of the alar cartilage. These defects within the middle crura will require stabilization with a columellar strut and, often, coverage with a concealer tip graft. We speculate that the cause of these defects is a disruption of the hedgehog signals that may arrest the condensation or block the differentiation of the underlying neural crest cells.

Potential therapeutic Strategies and Its Application in Correcting Birth Defects, Craniosynostosis, Neurological Disorders and Other Diseases

Background: Gene Therapy (GT) aims to fix a disease linked with genetic abnormality. Gene Therapy (GT) is currently receiving an attention from scientists, clinicians and the general public in an attempt to correct genetic defects. It including with congenital abnormalities, craniosynostosis (syndromic and nonsyndromic), craniofacial deformity, and neurodevelopmental disorders. However, its application is beset with complications partly because of lack of advanced knowledge, research and partly because of vested interest by the society. Objective: This study is an attempt to highlight some of the major benefits of gene therapy which leads to define the role played by medical informatics in facilitating rational use of gene therapy. Materials and methods: An attempt was made to review major studies in the international literature to synthesize the potential risks, benefits of gene therapy. We also reviewed the tools and techniques in this field of medical informatics. W hich can be employed for spreading awareness about gene therapy among common people? We developed a conceptual model of matching the key concepts with the current protocols used in the field of medical informatics. Results: GT offers a new hope for the treatment of birth defects, neurodegenerative disorders like Huntingtons disease. Its application in Parkinsons disease has moved a step closer to acceptance in the wake of its successful double blind clinical trial. The educational media, fall under four categories, viz., audio media, the visual media, the audio-visual and the virtual-media in vitro and vivo. The simulation and animation capabilities of the media are quite helpful in the conceptualization of gene therapy. The audio-visual media are useful for counseling in matter of genetic disorders the public. Conclusion: Our study suggests that an integrated and holistic approach of medical informatics. It can be highly beneficial for the advanced application of gene therapy in the years to come. G T has become debatable and often controversial because of tendency to use for manipulating the desirable attributes. Moreover, its rational use is likely to benefit the mankind.