A Rare Case of Mosaic 3pter and 5pter Deletion-Duplication with Autism Spectrum Disorder and Dyskinesia.

Introduction: There is evidence that neurodevelopmental disorders are associated with chromosomal abnormalities. Current genetic testing can clinch an exact diagnosis in 20-25% of such cases. Case Description. A 3 years and 11 months old boy with global developmental delay had repetitive behaviors and hyperkinetic movements. He was stunted and underweight. He had ataxia, limb dyskinesia, triangular face, microcephaly, upward slanting palpebral fissure, hypertelorism, retrognathia, posteriorly rotated ears, long philtrum, thin lips, broad nasal tip, polydactyly, tappering fingers, and decreased tone in the upper and lower limbs with normal deep tendon reflexes. Magnetic resonance imaging of the brain, ultrasound of the abdomen, and ophthalmological evaluation were normal. Brain evoked response auditory revealed bilateral moderate hearing loss. He fulfilled the Diagnostic Statistical Manual 5 criteria for autism. In the Vineland Social Maturity Scale, his score indicated a severe delay in social functioning. His genetic evaluation included karyotyping, fluorescence in situ hybridization (FISH), and chromosomal microarray analysis (CMA). The karyotype report from high-resolution lymphocyte cultures was mos 46, XY, der(3)t(3; 5)(p26; p15.3)[50]/46, XY,der(5) t(3;5) (p26;p15.3)[50].ish. His karyotype report showed a very rare and abnormal mosaic pattern with two cell lines (50% each). Cell-line#1: 3pter deletion with 5pter duplication (3pter-/5pter+) and cell-line#2: 3pter duplication with 5pter deletion (3pter+/5pter-) derived from a de novo reciprocal translocation t(3; 5)(p26; p15.3) which was confirmed by FISH. The chromosomal microarray analysis report was normal. The two cell lines (50% each) seem to have balanced out at the whole genome level. Occupational, sensory integration, and behavior modification therapy were initiated for his autistic features, and anticholinergic trihexiphenidyl was prescribed for hyperkinetic movements. Conclusion: This case highlights a rare genetic finding and the need for timely genetic testing in a child with dysmorphism and autism with movement disorder to enable appropriate management and genetic counselling.

Morphology-Tuned Electrochemical Immunosensing of a Breast Cancer Biomarker Using Hierarchical Palladium Nanostructured Interfaces.

Metallic nanostructures are considered attractive candidates for designing novel biosensors due to their enormously significant surface area, accelerated kinetics, and improved affinity. Controllable morphological tuning of metallic nanostructures on sensing interfaces is crucial for attaining clinically relevant sensitivity and exquisite selectivity in a complex biological environment. Therefore, a facile, convenient, and robust one-step electroreduction method was employed to develop different morphological variants of palladium (Pd) nanostructures supported onto oxidized carbon nanotubes to facilitate label-free electrochemical immunosensing of HER2. The morphological and structural attributes of the synthesized Pd nanostructures were thoroughly investigated using scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and atomic force microscopy techniques. In-depth electrochemical investigations revealed an intimate correlation between the nanostructured sensor and electrochemical response, suggesting the suitability of hierarchical palladium nanostructures supported onto carbon nanotubes [Pd(-0.1 V)/CNT] for sensitive detection of HER2. The high surface area of hierarchical Pd nanostructures enabled an ultrasensitive electrochemical response toward HER2 (detection limit: 1 ng/mL) with a wide detection range of 10 to 100 ng/mL. The ease of surface modification, sensitivity, and reliable electrochemical response in human plasma samples suggested the enormous potential of Pd nanostructuring for chip-level point-of-care screening of HER2-positive breast cancer patients.

Prenatal Diagnosis by Chromosome Microarray Analysis, An Indian Experience.

BACKGROUND: Karyotyping has been the gold standard for prenatal chromosome analysis. The resolution should be higher by chromosome microarray analysis (CMA). The challenge lies in recognizing benign and pathogenic or clinically significant copy number variations (pCNV) and variations of unknown significance (VOUS). The aim was to evaluate the diagnostic yield and clinical utility of CMA, to stratify the CMA results in various prenatal referral groups and to accumulate Indian data of pCNVs and VOUS for further interpretation to assist defined genetic counseling. METHODS: Karyotyping and CMA were performed on consecutive referrals of 370 prenatal samples of amniotic fluid (n = 274) and chorionic villi (n = 96) from Indian pregnant women with high maternal age (n = 23), biochemical screen positive (n = 61), previous child abnormal (n = 59), abnormal fetal ultrasound (n = 205) and heterozygous parents (n = 22). RESULTS AND CONCLUSION: The overall diagnostic yield of abnormal results was 5.40% by karyotyping and 9.18% by CMA. The highest percentage of pCNVs were found in the group with abnormal fetal ultrasound (5.40%) as compared to other groups, such as women with high maternal age (0.81%), biochemical screen positive (0.54%), previous abnormal offspring (0.81%) or heterozygous parents group (1.62%). Therefore, all women with abnormal fetal ultrasound must undergo CMA test for genotype-phenotype correlation. CMA detects known and rare deletion/duplication syndromes and characterizes marker chromosomes. Accumulation of CNV data will form an Indian Repository and also help to resolve the uncertainty of VOUS. Pretest and posttest genetic counseling is essential to convey benefits and limitations of CMA and help the patients to take informed decisions.

Recent advances in biosensing approaches for point-of-care breast cancer diagnostics: challenges and future prospects.

Timely and accurate diagnosis of breast cancer is essential for efficient treatment and the best possible survival rates. Biosensors have emerged as a smart diagnostic platform for the detection of biomarkers specific to the onset, recurrence, and therapeutic drug monitoring of breast cancer. There have been exciting recent developments, including significant improvements in the validation, sensitivity, specificity, and integration of sample processing steps to develop point-of-care (POC) integrated micro-total analysis systems for clinical settings. The present review highlights various biosensing modalities (electrical, optical, piezoelectric, mass, and acoustic sensing). It provides deep insights into their design principles, signal amplification strategies, and comparative performance analysis. Finally, this review emphasizes the status of existing integrated micro-total analysis systems (µ-TAS) for personalized breast cancer therapeutics and associated challenges and outlines the approach required to realize their successful translation into clinical settings.

Recent advances in nanomaterial-based electrochemical detection of antibiotics: Challenges and future perspectives.

The continuous need for food resources by humans and animals has led to extensive use of antibiotics as essential medicines. However, we are now facing serious environmental contamination of antibiotics and the associated health concerns because of their uncontrolled disposal. In an effort to resolve this problem, nanostructured electrochemical platforms comprising of diverse materials (e.g., carbonaceous nanoparticles, metal nanoparticles, magnetic nanoparticles, metal-organic frameworks, and quantum dots) have been proposed to detect antibiotic residues. Despite the significant progress achieved in such research fields, further efforts are still required to develop advanced electrochemical sensors with the aid of multi-functional nanomaterials and to ensure efficient portability for such sensors with enhaced communicability. Therefore, the present review summarizes an in-depth evaluation of the nanostructured electrochemical sensing system for antibiotics residues in diverse matrices (e.g., human fluids, environmental media, and food/beverages samples). The present review begins with a brief introduction to antibiotics followed by a survey on the existing electroanalytical techniques to highlight the significance of nanomaterial-based electrochemical sensing techniques for antibiotics in diverse matrices. Finally, the review provides an outlook on the future concepts of this research field to help upgrade the sensing techniques for antibiotics.

Extending the Phenotype and Identification of a Novel Candidate Gene for Immunodeficiency in 5q11 Microdeletion Syndrome.

Array CGH has led to the delineation of innumerable microdeletion syndromes. We present a patient with a 7-Mb deletion at 5q11.2 with previously unreported features, such as immunodeficiency, asymmetry of hands and feet, joint laxity, and agenesis of corpus callosum. The clinical features of this patient are compared with 13 patients reported previously. A common critical region (CCR) of 1.4 Mb (54-55.4 Mb) is defined in all cases including the present one. Of the 14 genes present in CCR, IL6ST is proposed to be the candidate gene for immunodeficiency observed in some of these patients. IL6ST encodes gp130, a signal transduction protein for various interleukins and cytokines. It is involved in the generation of both T and B lymphocytes as well as the production of acute-phase reactants. Microdeletion 5q11.2 should be considered as a recognisable syndrome based on the common phenotype and the novel features described.

Helping to build and rebuild secure lives and futures: financial transfers from parents to adult children and grandchildren.

This paper explores intergenerational financial transfers from parents to adult children and grandchildren within a life course perspective. Research on intergenerational financial transfers has been sparse, and little is known about the financial support older Canadians provide to family members or about the meaning of that assistance. Survey data from a convenience sample of older Canadians was analysed to determine the types of financial assistance older persons provide, what motivates them to provide this assistance, and what meanings such transfers have for the older persons themselves. Findings suggest that it is often events and transitions in the lives of adult children that shape the financial assistance that is needed and given within these families. Older parents demonstrate a strong desire to help their children and grandchildren through important or difficult transitions to "build or rebuild secure lives and futures". Parents' assistance is also influenced by their own family history of assistance and their desire to pass on an early inheritance during their lifetime.

A critical analysis of the broker and strengths models of case management: identifying a potential framework for community case managers.

In Canada, case management has been applied to a variety of health care settings including the community care system, where case managers have become an integral component in the delivery of government-funded, in-home services. Specifically in Ontario, home care is accessed through 43 Community Care Access Centres (CCACs), and the model currently driving case management practices most closely resembles the Broker model. Not only does this create moral distress among the case managers, but it also hinders their ability to meet the health care needs of the community as current cost containment strategies can lead to suffering and emotional distress for a significant portion of the people who are cut from care. This article will identify a potential framework for case managers in CCACs. The Strengths model offers a framework that is consistent with the goals of Ontario case managers and is committed to client autonomy, empowerment, and client-driven care. Given the multitude of health care challenges facing CCAC case managers today, the Strengths model of practice has the potential to contain and maintain costs without compromising the psychological wellbeing and health care needs of the community.