Phenotypic Characterization of Intellectual Disability Caused by MBOAT7 Mutation in Two Consanguineous Pakistani Families

A homozygous in-frame deletion (c. 758_778del; p. Glu253_Ala259del) in membrane-bound O-acyltransferase family member 7 (MBOAT7), also known as lysophosphatidylinositol acyltransferase (LPIAT1), was previously reported to be the genetic cause of intellectual disability (ID) in consanguineous families from Pakistan. Here, we identified two additional Pakistani consanguineous families with severe ID individuals sharing the same homozygous variant. Thus, we provide further evidence to support this MBOAT7 mutation as a potential founder variant. To understand the genotype-phenotype relationships of the in-frame deletion in the MBOAT7 gene, we located the variant in the fifth transmembrane domain of the protein and determined that it causes steric hindrance to the formation of an α-helix and hydrogen bond, possibly influencing its effectiveness as a functional transmembrane protein. Moreover, extensive neuropsychological observations, clinical interviews and genetic analysis were performed on 6 patients from the 2 families. We characterized the phenotype of the patients and noted the serious outcome of severe paraplegia. Thus, optimal management for symptom alleviation and appropriate screening in these patients are crucial.

Heterogeneity of MSI-H gastric cancer identifies a subtype with worse survival

BackgroundMicrosatellite instability-high (MSI-H) tumour patients generally have a better prognosis than microsatellite-stable (MSS) ones due to the large number of non-synonymous mutations. However, an increasing number of studies have revealed that less than half of MSI-H patients gain survival benefits or symptom alleviation from immune checkpoint-blockade treatment. Thus, an in-depth inspection of heterogeneous MSI-H tumours is urgently required.MethodsHere, we used non-negative matrix factorisation (non-NMF)-based consensus clustering to define stomach adenocarcinoma (STAD) MSI-H subtypes in samples from The Cancer Genome Atlas and an Asian cohort, GSE62254.ResultsMSI-H STAD samples are basically clustered into two subgroups (MSI-H1 and MSI-H2). Further examination of the immune landscape showed that immune suppression factors were enriched in the MSI-H1 subgroup, which may be associated with the poor prognosis in this subgroup.ConclusionsOur results illustrate the genetic heterogeneity within MSI-H STADs, with important implications for cancer patient risk stratification, prognosis and treatment.

The Experience of Symptom Cluster and Symptom Alleviation Self-Care in Patients with Head and Neck Cancer: A Qualitative Study

Patients with head and neck cancer usually experience physical and psychological changes and adjustments related to the disease and management of therapy. The patients will experience symptom cluster and will use effective symptom alleviation self-care to relieve the symptoms. The proper identification of symptom cluster and the effectiveness of using symptom alleviation self-care will be the basis for the success of disease management. This study aimed to investigate the symptom cluster and symptom alleviation self-care in patients with head and neck cancer, and which has an impact on the quality of life. This research was a pilot study using a qualitative design and involved five patients at the public hospital in Semarang, Indonesia. The qualitative design has been chosen to explore the varied of symptom experienced by the patients about the nature, number, location, duration and intensity of experiences, which may different experiences of symptom cluster and symptom alleviation self-care for each patient with Head and Neck Cancer. Data were collected through semi-structured interviews and analyzed used the qualitative content analysis process. Three themes were identified in this study, including: the patients’ experience of symptom cluster, the patients’ experience of symptom alleviation self-care, and the impaired quality of life domain. The results of this study showed that the patients’ experience sickness and gastrointestinal symptom cluster during illness and undergoing therapy, as well as variations in the symptom alleviation self-care, including: diet/ nutrition/ lifestyle changes, mind/ body/ spiritual control, biological treatment, herbal treatment, and prescribed medicine. The symptom cluster and symptom alleviation self-care has an impact on the patients’ outcome that is the quality of life. This study showed that the experience of symptom cluster and symptom alleviation self-care varied and highly individualized, which has an impact on the quality of life. The importance of proper identification about symptom cluster and the effectiveness of using symptom alleviation self-care by the nurses will be the basis for the success of disease management to improve the patients’ quality of life. Therefore, optimizing the nurses’ role is needed as the basis for the development of symptom management nursing programs.

Protein Chimera-based Ca2+ Rewiring as a Treatment Modality for Neurodegeneration

Calcium is a versatile signaling molecule; a key regulator of an array of diverse cellular processes ranging from transcription to motility to apoptosis. It plays a critical role in neuronal signal transmission and energy metabolism through specialized mechanisms. Dysregulation of the Ca2+ signaling pathways has been linked to major psychiatric diseases. Here, we focus on molecular psychiatry, exploring the role of calcium signaling in neurological disease development and aggravation, specifically in Alzheimer’s and Huntington’s diseases. Understanding the molecular underpinnings helps us first to identify common mechanistic patterns, and second to develop targeted therapeutics for symptom alleviation. Specifically, we propose potential protein-level hallmarks of dysregulation that can be targeted using calcium-based chimeras (synthetic fusions of unrelated modular proteins) for localized pharmacotherapy.

Goals of care and treatment in terminal delirium: A qualitative study of the views and experiences of healthcare professionals caring for patients with cancer

ObjectiveThis study explores the views of healthcare professionals regarding care and treatment goals in irreversible terminal delirium and their effect on patients and caregivers.MethodWe conducted a qualitative interview study of healthcare professionals (palliative care physician, oncologist, psycho-oncologist, and clinical psychologist) engaged in the treatment of terminally ill cancer patients. We assessed the views of healthcare workers regarding treatment goals in terminal delirium and their effect on patients and their families.ResultOf the 21 eligible healthcare professionals, 20 agreed to participate in this study. Three of the professionals had experience with treating terminal delirium as family caregivers. We identified five important aspects of treatment goals in terminal delirium based on the views of healthcare professionals: (1) adequate management of symptoms/distress, (2) ability to communicate, (3) continuity of self, (4) provision of care and support to families, and (5) considering a balance (between symptom alleviation and maintaining communication; between symptom alleviation and family preparations for the death of patients; balance between specific treatment goals for delirium and general treatment goals).Significance of resultsAccording to the views of healthcare workers questioned in this study, goals of care and treatment in terminal delirium are multidimensional and extend beyond simply controlling patient symptoms.