Baldwinbanke1387

To assess the presence of clinically actionable results and other genetic findings in an otherwise healthy population of adults seen in a medical practice setting and offered "predictive" genomic testing.

In 2014, a predictive genomics clinic for generally healthy adults was launched through the Mayo Clinic Executive Health Program. Self-identified interested patients met with a genomic nurse and genetic counselor for pretest advice and education. Two genome sequencing platforms and one gene panel-based health screen were offered. Posttest genetic counseling was available for patients who elected testing. From March 1, 2014, through June 1, 2019, 1281 patients were seen and 301 (23.5%) chose testing. Uptake rates increased to 36.3% [70 of 193]) in 2019 from 11.8% [2 of 17] in 2014. Clinically actionable results and genetic findings were analyzed using descriptive statistics.

Clinically actionable results were detected in 11.6% of patients (35 of 301), and of those, 51.7% (15 of 29) with a cancer or cardc services could be beneficial in medical practice, although additional studies are needed.Mechanical stress during cell migration may be a previously unappreciated source of genome instability, but the extent to which this happens in any animal in vivo remains unknown. We consider an in vivo system where the adult stem cells of planarian flatworms are required to migrate to a distal wound site. We observe a relationship between adult stem cell migration and ongoing DNA damage and repair during tissue regeneration. Migrating planarian stem cells undergo changes in nuclear shape and exhibit increased levels of DNA damage. Increased DNA damage levels reduce once stem cells reach the wound site. Stem cells in which DNA damage is induced prior to wounding take longer to initiate migration and migrating stem cell populations are more sensitive to further DNA damage than stationary stem cells. RNAi-mediated knockdown of DNA repair pathway components blocks normal stem cell migration, confirming that active DNA repair pathways are required to allow successful migration to a distal wound site. Together these findings provide evidence that levels of migration-coupled-DNA-damage are significant in adult stem cells and that ongoing migration requires DNA repair mechanisms. Our findings reveal that migration of normal stem cells in vivo represents an unappreciated source of damage, which could be a significant source of mutations in animals during development or during long-term tissue homeostasis.The FOXM1 transcription factor is an oncoprotein and a top biomarker of poor prognosis in human cancer. Overexpression and activation of FOXM1 is frequent in high-grade serous carcinoma (HGSC), the most common and lethal form of human ovarian cancer, and is linked to copy number gains at chromosome 12p13.33. We show that FOXM1 is co-amplified and co-expressed with RHNO1, a gene involved in the ATR-Chk1 signaling pathway that functions in the DNA replication stress response. Selleckchem Epigenetic inhibitor We demonstrate that FOXM1 and RHNO1 are head-to-head (i.e., bidirectional) genes (BDG) regulated by a bidirectional promoter (BDP) (named F/R-BDP). FOXM1 and RHNO1 each promote oncogenic phenotypes in HGSC cells, including clonogenic growth, DNA homologous recombination repair, and poly-ADP ribosylase inhibitor resistance. FOXM1 and RHNO1 are one of the first examples of oncogenic BDG, and therapeutic targeting of FOXM1/RHNO1 BDG is a potential therapeutic approach for ovarian and other cancers.A new method for applying solid stress to aggregates of cells is shedding light on the impact of mechanical forces on cancer cells.Many enveloped viruses induce multinucleated cells (syncytia), reflective of membrane fusion events caused by the same machinery that underlies viral entry. link2 These syncytia are thought to facilitate replication and evasion of the host immune response. Here, we report that co-culture of human cells expressing the receptor ACE2 with cells expressing SARS-CoV-2 spike, results in synapse-like intercellular contacts that initiate cell-cell fusion, producing syncytia resembling those we identify in lungs of COVID-19 patients. To assess the mechanism of spike/ACE2-driven membrane fusion, we developed a microscopy-based, cell-cell fusion assay to screen ~6000 drugs and >30 spike variants. Together with quantitative cell biology approaches, the screen reveals an essential role for biophysical aspects of the membrane, particularly cholesterol-rich regions, in spike-mediated fusion, which extends to replication-competent SARS-CoV-2 isolates. Our findings potentially provide a molecular basis for positive outcomes reported in COVID-19 patients taking statins and suggest new strategies for therapeutics targeting the membrane of SARS-CoV-2 and other fusogenic viruses.Disruption of the circadian clock machinery in cancer cells is implicated in tumor malignancy. Studies on cancer therapy reveal the presence of heterogeneous cells, including breast cancer stem-like cells (BCSCs), in breast tumors. BCSCs are often characterized by high aldehyde dehydrogenase (ALDH) activity, associated with the malignancy of cancers. In this study, we demonstrated the negative regulation of ALDH activity by the major circadian component CLOCK in murine breast cancer 4T1 cells. The expression of CLOCK was repressed in high-ALDH-activity 4T1, and enhancement of CLOCK expression abrogated their stemness properties, such as tumorigenicity and invasive potential. Furthermore, reduced expression of CLOCK in high-ALDH-activity 4T1 was post-transcriptionally regulated by microRNA miR-182. Knockout of miR-182 restored the expression of CLOCK, resulted in preventing tumor growth. Our findings suggest that increased expression of CLOCK in BCSCs by targeting post-transcriptional regulation overcame stemness-related malignancy and may be a novel strategy for breast cancer treatments.

Little is known about perceived health status and behavioral risk factors among prostate cancer survivors. The objective of this study was to describe racial and ethnic differences in self-reported health status, chronic conditions, and selected behavioral risk factors among prostate cancer survivors in the US.

We used data from the 2015 National Health Interview Survey to calculate the prevalence of various levels of health status, chronic conditions, behavioral risk factors, and sociodemographic characteristics among prostate cancer survivors aged 50 years or older. We stratified results by race and ethnicity.

Of the 317 prostate cancer survivors in our sample, 33.1% reported no physical activity, 64.2% reported being current drinkers, 26.1% characterized their drinking as moderate/heavy, 42.3% reported being former smokers, and 8.7% were current smokers. Nearly one-third (29.1%) of survivors were obese (body mass index ≥30), and 15.1% had 3 to 6 chronic conditions. A greater percentage of White (29.7ve health behaviors among prostate cancer survivors and use targeted interventions to address disparities.SARS-CoV-2 variants of concern (VOC) should not escape molecular surveillance. link3 We investigated if SARS-CoV-2 rapid antigen tests (RATs) could detect B.1.1.7 and B.1.351 VOCs in certain laboratory conditions. Infectious cell culture supernatants containing B.1.1.7, B.1.351 or non-VOC SARS-CoV-2 were respectively diluted both in DMEM and saliva. Dilutions were analysed with Roche, Siemens, Abbott, nal von minden and RapiGEN RATs. While further studies with appropriate real-life clinical samples are warranted, all RATs detected B.1.1.7 and B.1.351, generally comparable to non-VOC strain.We compared 19,207 cases of SARS-CoV-2 variant B.1.1.7/S gene target failure (SGTF), 436 B.1.351 and 352 P.1 to non-variant cases reported by seven European countries. COVID-19 cases with these variants had significantly higher adjusted odds ratios for hospitalisation (B.1.1.7/SGTF 1.7, 95% confidence interval (CI) 1.0-2.9; B.1.351 3.6, 95% CI 2.1-6.2; P.1 2.6, 95% CI 1.4-4.8) and B.1.1.7/SGTF and P.1 cases also for intensive care admission (B.1.1.7/SGTF 2.3, 95% CI 1.4-3.5; P.1 2.2, 95% CI 1.7-2.8).

Social determinants of health have the potential to influence mental health and addictions-related emergency department (ED) visits and the likelihood of admission to hospital. We aimed to determine how social determinants of health, individually and in combination, relate to the likelihood of hospital admission at the time of postpartum psychiatric ED visits.

Among 10 702 postpartum individuals (female based on health card) presenting to the ED for a psychiatric reason in Ontario, Canada (2008-2017), we evaluated the relation between six social determinants of health (age, neighbourhood quintile [Q, Q1 = lowest, Q5 = highest], rurality, immigrant category, Chinese or South Asian ethnicity and neighbourhood ethnic diversity) and the likelihood of hospital admission from the ED. Poisson regression models generated relative risks (RR, 95% CI) of admission for each social determinant, crude and adjusted for clinical severity (diagnosis and acuity) and other potential confounders. Generalised estimating equation from the ED depended primarily on the clinical severity of presentation, not on individual or intersecting social determinants of health. Being of Chinese ethnicity did increase the likelihood of admission independent of clinical severity and other measured factors; the reasons for this warrant further exploration.

For the most part, whether a postpartum ED visit resulted in admission from the ED depended primarily on the clinical severity of presentation, not on individual or intersecting social determinants of health. Being of Chinese ethnicity did increase the likelihood of admission independent of clinical severity and other measured factors; the reasons for this warrant further exploration.Institutionalization is a current problem, related to several indicators of psychological maladjustment. In the same way, there are several studies that point to the role of shame and self-criticism in the development of psychopathology. Therefore, our study explored, in institutionalized adolescents, whether early memories of warmth and safeness (EMWS) were associated to depression through external shame and self-criticism. The sample included 171 institutionalized adolescents (60.2% girls; Mage = 15.56; SD = 1.49). Depression, EMWS, external shame and self-criticism were assessed. The EMWS didn't show a direct effect on depression, exerting its effect indirectly through external shame and self-criticism. The relationship between EMWS and self-criticism was fully mediated by external shame, and the relationship between external shame and depression was fully mediated by self-criticism. In conclusion, the way the individual sees and relates to the self seems to impact on psychological adjustment and in the development of psychopathology. The fact that external shame and self-criticism fully mediated the relationship between EMWS and depression emphasizes the relevance of preventive and therapeutic approaches that aim to promote a healthier way of relating to the self.

The study examined the diagnosis experience of midlife family caregivers of a patient with a blood cancer, exploring similarities and differences between parent caregivers and adult-child caregivers.

Participants were between 30 and 65 years old and were family caregivers of a living patient with acute myeloid leukemia, acute lymphoblastic leukemia, or lymphoma. We conducted semi-structured interviews with parent caregivers (n = 20) and adult-child caregivers (n = 19) and a thematic analysis of the interview data.

Both types of caregivers report the patient experiencing (1) mis- and missed diagnosis (facing delayed diagnosis or treatment and having symptoms dismissed or overlooked) and (2) emotional distress (being in shock and survival mode, struggling with uncertainty, and confronting mortality). Adult-child caregivers also experienced relational shifts in assuming control of their parent's care, sometimes despite geographic distance, and struggled to distribute the care burden among family members.

Differences between the caregivers' experiences emerged based on the relational role and the patient's place in the lifespan.