Time is of the essence: the molecular mechanisms of primary microcephaly

Primary microcephaly is a brain growth disorder characterized by a severe reduction of brain size and thinning of the cerebral cortex. Many primary microcephaly mutations occur in genes that encode centrosome proteins, highlighting an important role for centrosomes in cortical development. Centrosomes are microtubule organizing centers that participate in several processes, including controlling polarity, catalyzing spindle assembly in mitosis, and building primary cilia. Understanding which of these processes are altered and how these disruptions contribute to microcephaly pathogenesis is a central unresolved question. In this review, we revisit the different models that have been proposed to explain how centrosome dysfunction impairs cortical development. We review the evidence supporting a unified model in which centrosome defects reduce cell proliferation in the developing cortex by prolonging mitosis and activating a mitotic surveillance pathway. Finally, we also extend our discussion to centrosome-independent microcephaly mutations, such as those involved in DNA replication and repair.

The Role of Nasyiatul Aisyiyah and Fatayat NU Cadres in Preventing Stunting Cases in Indonesia

Stunting is a growth disorder caused by a lack of nutritional intake in toddlers. The factors that cause stunting in developing countries are not giving exclusive breastfeeding, socio-economic constraints, lack of mother's knowledge, and infectious diseases to poor environmental sanitation. The role of Nasyiatul Aisyiyah dan Fatayat NU cadres is needed to eliminate the stunting case in Indonesia. This article is aimed to elaborate on the role of Nasyiatul Aisyiyah and Fatayat NU to decrease stunting cases in Indonesia. This article uses a literature study research method by analyzing the role of Nasyiatul Aisyiyah dan Fatayat NU in Indonesia. In this article, it is stated that Nasyiatul Aisyiyah cadres actively prevent stunting by having the Nutrition House program which is one of the community-based models as an effort to develop food sovereignty and security. Meanwhile, Fatayat NU increases the involvement of community leaders in advocacy, communication, information, and education on family planning, also known as the Proud Kencana program. Thus, the role of Nasyiatul Aisyiyah and Fatayat NU cadres has made a positive contribution in preventing stunting cases in Indonesia.

Pentingnya Pemberian Asi Eksklusif Untuk Mencegah Stunting Pada Anak

Stunting is a linear growth disorder that is not appropriate for age. One of the factors causing stunting is not giving exclusive breastfeeding to infants (Sholihah, 2019) . Stunting prevalence A total of 151,398 children in South Sulawesi suffer from stunting or failure to thrive in 2020. They are spread over five districts with the highest stunting rates. Of the 24 regencies/cities in South Sulawesi, there are four regions with the highest stunting rates, namely in Bone Regency 43 percent, Enrekang 39 percent, Jeneponto 36 percent, Takalar 34 percent, and Bantaeng 33 percent (Head of the South Sulawesi Provincial Government Health Service). In the last year, there has been a reduction in the stunting rate of around 7000 cases. Meanwhile, last year, South Sulawesi was still in the top 10 with the highest stunting rate nationally. The goal is that participants are expected to be able to know about the importance of exclusive breastfeeding to prevent stunting in children. The method of community service is the planning, implementation, monitoring and evaluation stages. The target of the implementation of this service is 9 pregnant women. This implementation is assisted by various parties including the Head of Midwifery at the Paccing Health Center, Posyandu midwives and students to carry out community service. The results of community service found that pregnant women will apply it when the baby is born, starting from babies aged 0 to 6 months. The conclusion is that the community service carried out was successful in increasing exclusive breastfeeding to prevent stunting in children at the UPT Puskesmas Paccing Kab. Bone.

The Role of Social Support for Mother's Interest in Preventing Stunting

Stunting is a condition where the child's height is too low. Indonesia is ranked fifth in the world of stunting. Stunting is the result of a complex interaction of family, environment, socioeconomic, and culture including behavior related to interest in preventing stunting. Social Support is an interpersonal transaction that is shown by providing assistance to others. This study was conducted to determine the effect of social support role for mother interest in preventing stunting using primary data through focus group discussion and Depth Interview on pregnant mothers and mothers who have children ≤2 years.Used the concept of The Pland Behavior Theory as the basic theory of this study. The study was conducted in June 2017-July 2017 in several urban villages in Palembang. From seven informants conducted by Depth Interview, various proportion of social support received by informants.Overall social support plays a role in determining the interest of mothers to preventing stunting, All mothers are very interested in preventing stunting.The greatest influence in determining the mother's interest to prevent stunting is Behavioral Control aspect in terms of Perceived Power that is the sense and the emotional bond that the child is the most important part of a mother and the sense of not wanting the child to have a stunting growth disorder.

Diagnostic utility of next-generation sequencing-based panel testing in 543 patients with suspected skeletal dysplasia

Background Skeletal dysplasia is typically diagnosed using a combination of radiographic imaging, clinical examinations, and molecular testing. Identifying a molecular diagnosis for an individual with a skeletal dysplasia can lead to improved clinical care, guide future medical management and treatment, and inform assessment of risk for familial recurrence. The molecular diagnostic utility of multi-gene panel testing using next-generation sequencing (NGS) has not yet been characterized for an unselected population of individuals with suspected skeletal dysplasia. In this study, we retrospectively reviewed patient reports to assess the diagnostic yield, reported variant characteristics, impact of copy number variation, and performance in prenatal diagnostics of panel tests for variants in genes associated with skeletal dysplasia and growth disorders. Results Clinical reports of consecutive patients with a clinical indication of suspected skeletal dysplasia who underwent panel testing were examined. The 543 patients included in the study submitted samples for diagnostic genetic testing with an indication of suspected skeletal dysplasia or growth disorder and received one of three nested panel tests. A molecular diagnosis was established in 42.0% of patients (n = 228/543). Diagnostic variants were identified in 71 genes, nearly half of which (n = 35, 49.3%) contributed uniquely to a molecular diagnosis for a single patient in this cohort. Diagnostic yield was significantly higher among fetal samples (58.0%, n = 51/88) than postnatal samples (38.9%, n = 177/455; z = 3.32, p < 0.0009). Diagnostic variants in fetal cases were identified across 18 genes. Thirteen diagnostic CNVs were reported, representing 5.7% of diagnostic findings and ranging in size from 241-bp to whole chromosome aneuploidy. Additionally, 11.4% (36/315) of non-diagnostic patient reports had suspicious variants of unknown significance (VUS), in which additional family studies that provide segregation data and/or functional characterization may result in reclassification to likely pathogenic. Conclusions These findings demonstrate the utility of panel testing for individuals with a suspected skeletal dysplasia or growth disorder, with a particularly high diagnostic yield seen in prenatal cases. Pursuing comprehensive panel testing with high-resolution CNV analysis can provide a diagnostic benefit, given the considerable phenotype overlap amongst skeletal dysplasia conditions.

THE IMPACT OF MALNUTRITION ON GROSS MOTORIC GROWTH OF THE CHILDREN WHOSE AGE BETWEEN 3 MONTHS AND 2 YEARS OLD

Background: Malnutrition was one of the health problems that ware a challenge for developing countries. This problem had an impact on all aspects including economic, social, and health status of the nation. From these impacts, other health problems can occur, namely child development disorders, including impaired gross motor development and fine motor. The purposeof this research is to determine the malnutrition against motor development Method: This study was a case control study. The amount of the sample was 106 children, their age were around 3 months till 2 years old in Pakis Surabaya Health Centre. Simple random sampling was the technic which researcher used to take the case sample and purposive sampling was for the control ones. The independent variable was children’s malnutrition and the dependent variable were gross and fine motoric growth of the children. Data collecting was done by observing the children with KPSP questioner. Researcher used Chi-square to analyze the data. Result: Malnutrition didn’t affect children’s gross motoric growth (p= 0.34) and fine motoric growth (0.26). Conclusion: In Pakis primary health center there were 33% children with malnutrition, 28.3% children with gross motoric growth disorder and 35.8% children with fine motoric growth disorder. There wasn’t any association between children’s malnutrition with gross and fine motoric growth of the children.

Diagnostic Utility of Next-Generation Sequencing-Based Panel Testing in 543 Patients with Suspected Skeletal Dysplasia

Background: Skeletal dysplasia is typically diagnosed using a combination of radiographic imaging, clinical examinations, and molecular testing. Identifying a molecular diagnosis for an individual with a skeletal dysplasia can lead to improved clinical care, guide future medical management and treatment, and inform assessment of risk for familial recurrence. The molecular diagnostic utility of multi-gene panel testing using next-generation sequencing (NGS) has not yet been characterized for an unselected population of individuals with suspected skeletal dysplasia. In this study, we retrospectively reviewed patient reports to assess the diagnostic yield, reported variant characteristics, impact of copy number variation, and performance in prenatal diagnostics of panel tests for variants in genes associated with skeletal dysplasia and growth disorders. Results: Clinical reports of consecutive patients with a clinical indication of suspected skeletal dysplasia who underwent panel testing were examined. The 543 patients included in the study submitted samples for diagnostic genetic testing with an indication of suspected skeletal dysplasia or growth disorder and received one of three nested panel tests. A molecular diagnosis was established in 42.0% of patients (n=228/543). Diagnostic variants were identified in 71 genes, nearly half of which (n=35, 49.3%) contributed uniquely to a molecular diagnosis for a single patient in this cohort. Diagnostic yield was significantly higher among fetal samples (58.0%, n=51/88) than postnatal samples (38.9%, n=177/455; z=3.32, p<0.0009). Diagnostic variants in fetal cases were identified across 18 genes. Thirteen diagnostic CNVs were reported, representing 5.7% of diagnostic findings and ranging in size from 241-bp to whole chromosome aneuploidy. Additionally, 11.4% (36/315) of non-diagnostic patient reports had suspicious variants of unknown significance (VUS), in which additional family studies that provide segregation data and/or functional characterization may result in reclassification to likely pathogenic. Conclusions: These findings demonstrate the utility of panel testing for individuals with a suspected skeletal dysplasia or growth disorder, with a particularly high diagnostic yield seen in prenatal cases. Pursuing comprehensive panel testing with high-resolution CNV analysis can provide a diagnostic benefit, given the considerable phenotype overlap amongst skeletal dysplasia conditions.

Automated Bone Age Assessment with Image Registration Using Hand X-ray Images

One of the methods for identifying growth disorder is by assessing the skeletal bone age. A child with a healthy growth rate will have approximately the same chronological and bone ages. It is important to detect any growth disorder as early as possible, so that mitigation treatment can be administered with less negative consequences. Recently, the most popular approach in assessing the discrepancy between bone and chronological ages is through the subjective protocol of Tanner–Whitehouse that assesses selected regions in the hand X-ray images. This approach relies heavily on the medical personnel experience, which produces a high intra-observer bias. Therefore, an automated bone age prediction system with image registration using hand X-ray images is proposed in order to complement the inexperienced doctors by providing the second opinion. The system relies on an optimized regression network using a novel residual separable convolution model. The regressor network requires an input image to be 299 × 299 pixels, which will be mapped to the predicted bone age through three modules of the Xception network. Moreover, the images will be pre-processed or registered first to a standardized and normalized pose using separable convolutional neural networks. Three steps image registration are performed by segmenting the hand regions, which will be rotated using angle calculated from four keypoints of interest, before positional alignment is applied to ensure the region of interest is located in the middle. The hand segmentation is based on DeepLab V3 plus architecture, while keypoints regressor for angle alignment is based on MobileNet V1 architecture, where both of them use separable convolution as the core operators. To avoid the pitfall of underfitting, synthetic data are generated while using various rotation angles, zooming factors, and shearing images in order to augment the training dataset. The experimental results show that the proposed method returns the lowest mean absolute error and mean squared error of 8.200 months and 121.902 months2, respectively. Hence, an error of less than one year is acceptable in predicting the bone age, which can serve as a good supplement tool for providing the second expert opinion. This work does not consider gender information, which is crucial in making a better prediction, as the male and female bone structures are naturally different.