Genetic backgrounds and clinical characteristics of congenital neutropenias in Israel.

BACKGROUND: Congenital neutropenias are characterized by severe infections and a high risk of myeloid transformation; the causative genes vary across ethnicities. The Israeli population is characterized by an ethnically diverse population with a high rate of consanguinity. OBJECTIVE: To evaluate the clinical and genetic spectrum of congenital neutropenias in Israel. METHODS: We included individuals with congenital neutropenias listed in the Israeli Inherited Bone Marrow Failure Registry. Sanger sequencing was performed for ELANE or G6PC3, and patients with wild-type ELANE/G6PC3 were referred for next-generation sequencing. RESULTS: Sixty-five patients with neutropenia were included. Of 51 patients with severe congenital neutropenia, 34 were genetically diagnosed, most commonly with variants in ELANE (15 patients). Nine patients had biallelic variants in G6PC3, all of consanguineous Muslim Arab origin. Other genes involved were SRP54, JAGN1, TAZ, and SLC37A4. Seven patients had cyclic neutropenia, all with pathogenic variants in ELANE, and seven had Shwachman-Diamond syndrome caused by biallelic SBDS variants. Eight patients (12%) developed myeloid transformation, including six patients with an unknown underlying genetic cause. Nineteen (29%) patients underwent hematopoietic stem cell transplantation, mostly due to insufficient response to treatment with granulocyte-colony stimulating factor or due to myeloid transformation. CONCLUSIONS: The genetic spectrum of congenital neutropenias in Israel is characterized by a high prevalence of G6PC3 variants and an absence of HAX1 mutations. Similar to other registries, for 26% of the patients, a molecular diagnosis was not achieved. However, myeloid transformation was common in this group, emphasizing the need for close follow-up.

Discomfort in Discussing Sexual Issues: Developing a New Scale for Staff at Long-Term Care Facilities for Older Adults.

Interviews reveal that many health professionals working with older adults are uncomfortable discussing sexual issues with those under their care. Nevertheless, to date, discomfort in discussing sexual issues with older adults has not been empirically investigated. To facilitate exploration of this subject, the current study evaluated the psychometric properties of a new measure: The Discomfort in Discussing Sexual Issues (DDSI) with Older Adults scale. The study was conducted via online survey among 127 long-term care staff (e.g., nurses, physicians, physical therapists, social workers, speech therapists, occupational therapists) serving older adults. A confirmatory factor analysis confirmed the DDSI scale's structure as a single, four-item construct. More conservative attitudes regarding sexuality in later life were associated with higher DDSI scores. In addition, DDSI scale scores were negatively correlated with knowledge about sexuality in later life and educational level. Findings indicate that the DDSI has good psychometric properties, as reflected by its high reliability and adequate validity, making it a useful assessment tool for future research. [Journal of Gerontological Nursing, 48(9), 27-37.].

The Role of Affect as a Mediator between Coping Resources and Heart Rate Variability among Older Adults.

BACKGROUND: Heart rate variability (HRV) has been suggested as an indicator of capacity to adapt effectively to physiological or environmental challenges and of physical and psychological health in old age. AIMS: The study assessed levels of high-frequency HRV (HF-HRV) among older adults in relation to positive and negative affect and the mediating role of positive and negative affect in the association between coping resources (perceived social support and sense of mastery) and HF-HRV. METHOD: Participants were 187 men and women in three assisted-living residences who were independent in activities of daily living (93.4% participation rate). The participants completed sense of mastery, multidimensional scale of perceived social support, and positive and negative affect questionnaires. HF-HRV was derived from electrocardiography data measured by a Holter monitoring device for 15 minutes. RESULTS: The empirical model showed good fit indices indicating that higher HF-HRV was associated with lower negative affect, and negative affect mediated the association between perceived social support and HF-HRV. In addition, perceived social support and sense of mastery were associated with higher positive affect and lower negative affect. CONCLUSIONS: Although this was a cross-sectional study, it suggests that HF-HRV may be a link between affect and health in old age. It also suggests the importance of identification and intervention with older adults and their support systems to reduce negative affect.

Comparison of Covid-19 antibody status after vaccination between residents in long-term geriatric care and residents assisted-living facilities.

OBJECTIVE: To compare 2 CoV-SARS-2 ('anti-s') antibody levels after vaccination between residents in long-term geriatric care (LTGC) and residents in assisted-living facilities who had received two doses of the BNT162b2 vaccine. SARS-CoV-2 serology was tested with Quant II IgG CoV-SARS-2. Blood samples were collected 3-4 months after administration of the second vaccine dose. RESULTS: Anti-s ≥ 50 AU/ml was found in 85.4% of 90 residents in LTGC (median 498 AU/ml) and 94.9% of 214 residents in assisted living (median 728 AU/ml). p = .006. Factors associated with anti-s < 300 AU/ml were multi-morbidity, diabetes mellitus and cancer.

Quantitative proteomics of rat livers shows that unrestricted feeding is stressful for proteostasis with implications on life span.

Studies in young mammals on the molecular effects of food restriction leading to prolong adult life are scares. Here, we used high-throughput quantitative proteomic analysis of whole rat livers to address the molecular basis for growth arrest and the apparent life-prolonging phenotype of the food restriction regimen. Over 1800 common proteins were significantly quantified in livers of ad libitum, restriction- and re-fed rats, which summed up into 92% of the total protein mass of the cells. Compared to restriction, ad libitum cells contained significantly less mitochondrial catabolic enzymes and more cytosolic and ER HSP90 and HSP70 chaperones, which are hallmarks of heat- and chemically-stressed tissues. Following re-feeding, levels of HSPs nearly reached ad libitum levels. The quantitative and qualitative protein values indicated that the restriction regimen was a least stressful condition that used minimal amounts of HSP-chaperones to maintain optimal protein homeostasis and sustain optimal life span. In contrast, the elevated levels of HSP-chaperones in ad libitum tissues were characteristic of a chronic stress, which in the long term could lead to early aging and shorter life span.

Growth attenuation is associated with histone deacetylase 10-induced autophagy in the liver.

Our previous data suggested that the histone deacetylase (HDAC) SIRT1 is involved in mediating the effect of nutrition on growth. The aim of the present research was to study the mechanism by which additional HDACs may be involved in nutrition-induced linear growth. The in vivo studies were performed in young male Sprague-Dawley rats that were either fed ad libitum (AL) or subjected to 10days of 40% food restriction (RES) and then refed (CU). For in vitro studies, Huh7 hepatoma cells were used. Food restriction led to significant reduction in liver weight, concomitant with increased autophagy (i.e., a decrease in the level of P62 and an increase in the expression level of Ambra1 and Atg16L2 genes in the RES group). At the same time, we found that the level of HDAC10 was significantly increased. Overexpression of HDAC10 in Huh7 hepatoma cells led to reduced cell viability and increased autophagy as shown by increased conversion of LC3-I to LC3-II. An increase in the level of HDAC10 was also obtained when mTOR was inhibited by Rapamycin. siRNA directed against HDAC10 abolished the effect of Rapamycin on cell viability and Ambra1 and Atg16L2 increased expression. These results suggest that increased levels of HDAC10 may mediate the effect of malnutrition on growth attenuation and autophagy. Deciphering the role of epigenetic regulation in the nutrition-growth connection may pave the way for the development of new forms of treatment for children with growth disorders.