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Newborn screening (NBS) has been one of the big innovations in public health. It has grown over the decades, especially with the introduction of tandem mass spectrometry. However, it is likely to expand significantly in the coming decades with the introduction of genomic testing. Traditionally, in NBS, there has been a pattern of repeat testing for confirmation and follow-up diagnostic testing. This follow-up is critical as NBS is a screening program. This pathway is appropriate for low-cost tests, but if public health authorities are going to invest in high-cost screening such as whole-genome sequencing, they are likely to baulk at repeating these expensive tests in a diagnostic setting. Our study investigates whether screening-grade data from NBS can be transitioned into diagnostic-grade data using a panel of single-nucleotide variants (SNVs) on a diagnostic specimen. These SNVs could be used to link the diagnostic specimen with all of the provenance requirements associated with routine pathology and the NBS genomic data. This strategy has large cost benefits and opens up the rapid use of NBS genomic data should a child present in an acute care setting and a genetic diagnosis is suspected. This approach will greatly speed up the confirmation of positive NBS results and reduce family anxiety due to delayed diagnostic testing. [ABSTRACT FROM AUTHOR]

This study, framed by the GRPI (Goal, Role, Process, and Interaction) teamwork model, explores team dynamics among nursing students in performing group assignments, utilizing a qualitative research design. Twenty-three nursing students from Year 1 to Year 4 at a nursing school in Macau were invited. Semi-structured personal interviews were carried out. In addition, three teachers who were involved in instructing and assessing group assignments of nursing students were also interviewed. Data were analyzed using inductive and deductive approaches. The study found that although the barriers to accomplishing effective teamwork were embedded into the four dimensions of the DRPI model, they were interplayed. Communication was fundamental for teamwork, thus leading to a modified DRPI model. Teammates did not equally share the workload. Despite interpersonal conflicts among teammates, nursing students managed to stay in superficial harmony with their peers. They became more familiar with teamwork while advancing into their senior years but with decreased group communications. This study highlights various factors preventing students from transferring individualism to team players. Teaming is not an equal learning opportunity for teammates. Culturally upheld value of harmony prevails in the interpersonal relationships of the team members, which may compromise the teamwork spirit cultivation expectations from the teachers. [ABSTRACT FROM AUTHOR]

Gene mutations that preferentially affect the CNS have been implicated in a number of neurological disorders. This leads to the possibility that a disease-causing mutation present only in CNS tissues could be missed if it were tested in a blood DNA sample only. The commonest mutation in amyotrophic lateral sclerosis (ALS) is an expansion of the hexanucleotide repeats of C9orf72. To find out if CNS-specific mutations of this gene could cause some cases of ALS we looked for differences in the size of C9orf72 repeats between DNA from the CNS and from white blood cells (WBCs) of 38 sporadic ALS patients, using a repeat-primed PCR screening test. We also looked for differences in C9orf72 repeats in WBC DNA from 6 ALS-discordant and 1 ALS-concordant monozygotic twins. Abnormally expanded C9orf72 repeats were found in 13% of the ALS CNS samples, as well as in their paired WBC DNA. The 87% of ALS CNS samples with normal-sized C9orf72 repeats had the same number of repeats in paired WBC samples. All ALS-discordant twins had the same normal numbers of WBC C9orf72 repeats. Although previous work suggests some tissue mosaicism in C9orf72 repeat size is probably present, this study indicates that this is not likely to be of sufficient magnitude to result in a normal C9orf72 repeat length in blood but an abnormally expanded repeat length in the CNS. This suggests that a blood DNA test alone will usually be sufficient to make a diagnosis of C9orf72 repeat-related ALS. [ABSTRACT FROM AUTHOR]

Objectives: To report novel biallelic PI4KA variants in a family presenting with pure hereditary spastic paraparesis., Methods: Two affected sisters presented with unsolved hereditary spastic paraparesis and underwent clinical and imaging assessments. This was followed by short-read next-generation sequencing., Results: Analysis of next-generation sequencing data uncovered compound heterozygous variants in PI4KA (NM_058004.4: c.[3883C>A];[5785A>C]; p.[(His1295Asn);(Thr1929Pro)]. Using ACMG guidelines, both variants were classified as likely pathogenic., Discussion: Here, next-generation sequencing revealed 2 novel compound heterozygous variants in the phosphatidylinositol 4-kinase alpha gene ( PI4KA ) in 2 sisters presenting with progressive pure hereditary spastic paraparesis. Pathogenic variants in PI4KA have previously been associated with a spectrum of disorders including autosomal recessive perisylvian polymicrogyria, with cerebellar hypoplasia, arthrogryposis, and pure spastic paraplegia. The cases presented in this study expand the phenotypic spectrum associated with PI4KA variants and contribute new likely pathogenic variants for testing in patients with otherwise unsolved hereditary spastic paraparesis., Competing Interests: J.M. Parmar is supported by the Australian Government Research Training Program. G. Ravenscroft is supported by an Australian NHMRC EL2 Fellowship (APP2007769). All other authors report no disclosures relevant to the manuscript. Go to Neurology.org/NG for full disclosures., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Health literacy has been identified as one vital determinant of public health and healthy behaviors, but very few studies regarding infectious disease prevention have been found. This descriptive cross-sectional study aimed to validate the pathway of infectious disease-specific health literacy (IDSHL), COVID-19 (coronavirus disease 2019) preventive behaviors, and their determinants. A sample of 1459 casino workers in Macao was eligible for analysis. The concept model was verified with a comparative fit index of 0.937 and goodness-of-fit index of 0.971. Government responses was a significant determinant of situational factors (helpfulness of health information, resource accessibility, and organizational training adequacy), while situational factors showed a direct effect on COVID-19 preventive behaviors. Education and organization training adequacy was the strongest influencing factor of IDSHL, which should be a key target of intervention programs for COVID-19.

Diagnostic applications of DNA sequencing technologies present a powerful tool for the clinical management of patients. Applications range from better diagnostic classification to identification of therapeutic options, prediction of drug response and toxicity, and carrier testing. Although the advent of massively parallel sequencing technologies has increased the complexity of clinical interpretation of sequence variants by an order of magnitude, the annotation and interpretation of the clinical effects of identified genomic variants remain a challenge regardless of the sequencing technologies used to identify them. Here, we survey methodologies which assist in the diagnostic classification of DNA variants and propose a practical decision analytic protocol to assist in the classification of sequencing variants in a clinical setting. The methods include database queries, software tools for protein consequence, evolutionary conservation and pathogenicity prediction, familial segregation, case-control studies, and literature review. These methods are deliberately pragmatic as diagnostic constraints of clinically useful turnaround times generally preclude obtaining evidence from in vivo or in vitro functional experiments for variant assessment. Clinical considerations require that variant classification is stringent and rigorous, as misinterpretation may lead to inappropriate clinical consequences; thus, multiple parameters and lines of evidence are considered to determine potential biological significance.

The TGF-beta family members are generated as latent pre-pro-polypeptides. The active mature peptides are cleaved from the latent forms by cellular proteases. TGF-beta 1, for instance, is predominantly processed by a substilisin-like proprotein convertase, furin. TGF-beta 2 has a consensus cleavage site for furin and therefore has been presumed to be cleaved by furin. However, TGF-beta 2 is often secreted as the latent form, which appears to be inconsistent with its postulated sensitivity to furin. We report here that both the regular (short) form of TGF-beta2 and its spliced variant with an additional exon (long form) are insensitive to furin. NIH 3T3 and CHO cells were transfected with expression vectors containing the short or long form of TGF-beta 2 or a chimeric TGF-beta consisting of the TGF-beta1 LAP region, the TGF-beta 2 cleavage site and the TGF-beta 2 mature peptide. The constructs included a c-myc epitope tag in the N-terminal region of the mature peptide. The TGF-betas produced by the transfected cells were analyzed with Western blots and immunocytochemistry. The intracellular proteins harvested from these cells were incubated with furin. Furin only inefficiently cleaved both the long and short forms of TGF-beta 2, but efficiently processed the chimeric TGF-beta. This indicates that the insensitivity of both forms of TGF-beta 2 to furin is a consequence of the tertiary structure of their LAP regions rather than their cleavage site. This differential processing of TGF-beta1 and -beta 2 may be part of the mechanism that generates isoform-specific functions of the TGF-betas.