Relationships Among Occupation/Activity Patterns, Health and Stress Perceptions, and Life Orientation in Well Adults

Background: This study examined the relationships among activity choices, perceived health, stress, and life orientation (optimism-pessimism) in a general population of 675 healthy adults ranging in age from 18-91 years. The objective was to examine assumptions that occupational scientists and practitioners hold regarding the relationships among health factors and engagement in activities/occupations. Method: The study used four self-report measures, including a customized activity card sort that asked participants about both healthy and unhealthy activity patterns. Responses were then compared with the participants’ perceptions of overall health, stress levels, and degrees of optimism and pessimism (life orientation). Results: Major findings confirmed that being engaged in more activities overall is aligned with more optimally perceived health, positive life orientation, and lower stress. However, participation in unhealthy activities negatively affected overall health, stress perception, and life orientation. The study also confirmed that women tend to have higher perceived stress than men and that caring for others is associated with more positive health ratings. Conclusion: The amount and type of activity participation appears to matter for even healthy individuals in terms of overall health, stress perception, and life orientation. This study confirms the importance of participating in a wide repertoire of activities and underscores the need for practitioners to ask clients about engagement in unhealthy activities as well as healthy ones

ARC Newsletter Volume 1, Issue 2

https://digitalcommons.lasalle.edu/arc_newsletter/1001/thumbnail.jp

Interplay between ESR1/PIK3CA codon variants, oncogenic pathway alterations and clinical phenotype in patients with metastatic breast cancer (MBC): Comprehensive circulating tumor DNA (ctDNA) analysis

BACKGROUND: although being central for the biology and druggability of hormone-receptor positive, HER2 negative metastatic breast cancer (MBC), ESR1 and PIK3CA mutations are simplistically dichotomized as mutated or wild type in current clinical practice. METHODS: The study analyzed a multi-institutional cohort comprising 703 patients with luminal-like MBC characterized for circulating tumor DNA through next generation sequencing (NGS). Pathway classification was defined based on previous work (i.e., RTK, RAS, RAF, MEK, NRF2, ER, WNT, MYC, P53, cell cycle, notch, PI3K). Single nucleotide variations (SNVs) were annotated for their oncogenicity through OncoKB. Only pathogenic variants were included in the models. Associations among clinical characteristics, pathway classification, and ESR1/PIK3CA codon variants were explored. RESULTS: The results showed a differential pattern of associations for ESR1 and PIK3CA codon variants in terms of co-occurring pathway alterations patterns of metastatic dissemination, and prognosis. ESR1 537 was associated with SNVs in the ER and RAF pathways, CNVs in the MYC pathway and bone metastases, while ESR1 538 with SNVs in the cell cycle pathway and liver metastases. PIK3CA 1047 and 542 were associated with CNVs in the PI3K pathway and with bone metastases. CONCLUSIONS: The study demonstrated how ESR1 and PIK3CA codon variants, together with alterations in specific oncogenic pathways, can differentially impact the biology and clinical phenotype of luminal-like MBC. As novel endocrine therapy agents such as selective estrogen receptor degraders (SERDS) and PI3K inhibitors are being developed, these results highlight the pivotal role of ctDNA NGS to describe tumor evolution and optimize clinical decision making

Biochemical analysis of TssK, a core component of the bacterial Type VI secretion system, reveals distinct oligomeric states of TssK and identifies a TssK–TssFG subcomplex

Gram-negative bacteria use the Type VI secretion system (T6SS) to inject toxic proteins into rival bacteria or eukaryotic cells. However, the mechanism of the T6SS is incompletely understood. In the present study, we investigated a conserved component of the T6SS, TssK, using the antibacterial T6SS of Serratia marcescens as a model system. TssK was confirmed to be essential for effector secretion by the T6SS. The native protein, although not an integral membrane protein, appeared to localize to the inner membrane, consistent with its presence within a membrane-anchored assembly. Recombinant TssK purified from S. marcescens was found to exist in several stable oligomeric forms, namely trimer, hexamer and higher-order species. Native-level purification of TssK identified TssF and TssG as interacting proteins. TssF and TssG, conserved T6SS components of unknown function, were required for T6SS activity, but not for correct localization of TssK. A complex containing TssK, TssF and TssG was subsequently purified in vitro, confirming that these three proteins form a new subcomplex within the T6SS. Our findings provide new insight into the T6SS assembly, allowing us to propose a model whereby TssK recruits TssFG into the membrane-associated T6SS complex and different oligomeric states of TssK may contribute to the dynamic mechanism of the system

Circulating tumour DNA characterisation of invasive lobular carcinoma in patients with metastatic breast cancer

BACKGROUND: Limited data exist to characterise molecular differences in circulating tumour DNA (ctDNA) for patients with invasive lobular carcinoma (ILC). We analysed metastatic breast cancer patients with ctDNA testing to assess genomic differences among patients with ILC, invasive ductal carcinoma (IDC), and mixed histology. METHODS: We retrospectively analysed 980 clinically annotated patients (121 ILC, 792 IDC, and 67 mixed histology) from three academic centers with ctDNA evaluation by Guardant360™. Single nucleotide variations (SNVs), copy number variations (CNVs), and oncogenic pathways were compared across histologies. FINDINGS: ILC was significantly associated with HR+ HER2 negative and HER2 low. SNVs were higher in patients with ILC compared to IDC or mixed histology (Mann Whitney U test, P \u3c 0.05). In multivariable analysis, HR+ HER2 negative ILC was significantly associated with mutations in CDH1 (odds ratio (OR) 9.4, [95% CI 3.3-27.2]), ERBB2 (OR 3.6, [95% confidence interval (CI) 1.6-8.2]), and PTEN (OR 2.5, [95% CI 1.05-5.8]) genes. CDH1 mutations were not present in the mixed histology cohort. Mutations in the PI3K pathway genes (OR 1.76 95% CI [1.18-2.64]) were more common in patients with ILC. In an independent cohort of nearly 7000 metastatic breast cancer patients, CDH1 was significantly co-mutated with targetable alterations (PIK3CA, ERBB2) and mutations associated with endocrine resistance (ARID1A, NF1, RB1, ESR1, FGFR2) (Benjamini-Hochberg Procedure, all q \u3c 0.05). INTERPRETATION: Evaluation of ctDNA revealed differences in pathogenic alterations and oncogenic pathways across breast cancer histologies with implications for histologic classification and precision medicine treatment. FUNDING: Lynn Sage Cancer Research Foundation, OncoSET Precision Medicine Program, and UL1TR001422

I-LEEP Newsletter Volume 2, Issue 3

https://digitalcommons.lasalle.edu/ileep_newsletter/1006/thumbnail.jp

Kinetic power of quasars and statistical excess of MOJAVE superluminal motions

The MOJAVE survey contains 101 quasars with a total of 354 observed radio components that are different from the radio cores, among which 95% move with apparent projected superluminal velocities with respect to the core, and 45% have projected velocities larger than 10c (with a maximum velocity 60c). Doppler boosting effects are analyzed to determine the statistics of the superluminal motions. We integrate over all possible values of the Lorentz factor the values of the kinetic energy corresponding to each component. The calculation of the mass in the ejection is carried out by assuming the minimum energy state. This kinetic energy is multiplied by the frequency at which the portions of the jet fluid identified as "blobs" are produced. Hence, we estimate the average total power released by the quasars in the form of kinetic energy in the long term on pc-scales. RESULTS. A selection effect in which both the core and the blobs of the quasar are affected by huge Doppler-boosting enhancement increases the probability of finding a jet ejected within 10 degrees of the line of sight >~40 times above what one would expect for a random distribution of ejection, which explains the ratios of the very high projected velocities given above. The average total kinetic power of each MOJAVE quasar should be very high to obtain this distribution: ~7E47 erg/s. This amount is much higher than previous estimates of kinetic power on kpc-scales based on the analysis of cavities in X-ray gas or radio lobes in samples of objects of much lower radio luminosity but similar black hole masses. The kinetic power is a significant portion of the Eddington luminosity, on the order of the bolometric luminosity, and proportional on average to square root of the radio luminosity, although this correlation might be induced by Malmquist-like bias.Comment: Published in A&A; v2: minor changes to fit the published versio

AzTEC 1.1 mm Observations of the MBM12 Molecular Cloud

We present 1.1 mm observations of the dust continuum emission from the MBM12 high-latitude molecular cloud observed with the Astronomical Thermal Emission Camera (AzTEC) mounted on the James Clerk Maxwell Telescope on Mauna Kea, Hawaii. We surveyed a 6.34 deg$^2$ centered on MBM12, making this the largest area that has ever been surveyed in this region with submillimeter and millimeter telescopes. Eight secure individual sources were detected with a signal-to-noise ratio of over 4.4. These eight AzTEC sources can be considered to be real astronomical objects compared to the other candidates based on calculations of the false detection rate. The distribution of the detected 1.1 mm sources or compact 1.1 mm peaks is spatially anti-correlated with that of the 100 micronm emission and the $^{12}$CO emission. We detected the 1.1 mm dust continuum emitting sources associated with two classical T Tauri stars, LkHalpha262 and LkHalpha264. Observations of spectral energy distributions (SEDs) indicate that LkHalpha262 is likely to be Class II (pre-main-sequence star), but there are also indications that it could be a late Class I (protostar). A flared disk and a bipolar cavity in the models of Class I sources lead to more complicated SEDs. From the present AzTEC observations of the MBM12 region, it appears that other sources detected with AzTEC are likely to be extragalactic and located behind MBM12. Some of these have radio counterparts and their star formation rates are derived from a fit of the SEDs to the photometric evolution of galaxies in which the effects of a dusty interstellar medium have been included.Comment: 8 pages, 6 figures, The Astrophysical Journal, in pres

Prediagnostic Plasma Vitamin D Metabolites and Mortality among Patients with Prostate Cancer

Laboratory evidence suggests that vitamin D might influence prostate cancer prognosis.We examined the associations between prediagnostic plasma levels of 25(OH)vitamin D [25(OH)D] and 1,25(OH)(2) vitamin D [1,25(OH)(2)D] and mortality among 1822 participants of the Health Professionals Follow-up Study and Physicians' Health Study who were diagnosed with prostate cancer. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of total mortality (n = 595) and lethal prostate cancer (death from prostate cancer or development of bone metastases; n = 202). In models adjusted for age at diagnosis, BMI, physical activity, and smoking, we observed a HR of 1.22 (95% CI: 0.97, 1.54) for total mortality, comparing men in the lowest to the highest quartile of 25(OH)D. There was no association between 1,25(OH)(2)D and total mortality. Men with the lowest 25(OH)D quartile were more likely to die of their cancer (HR: 1.59; 95% CI: 1.06, 2.39) compared to those in the highest quartile (P(trend) = 0.006). This association was largely explained by the association between low 25(OH)D levels and advanced cancer stage and higher Gleason score, suggesting that these variables may mediate the influence of 25(OH)D on prognosis. The association also tended to be stronger among patients with samples collected within five years of cancer diagnosis. 1,25(OH)(2)D levels were not associated with lethal prostate cancer.Although potential bias of less advanced disease due to more screening activity among men with high 25(OH)D levels cannot be ruled out, higher prediagnostic plasma 25(OH)D might be associated with improved prostate cancer prognosis

Trapped lipopolysaccharide and LptD intermediates reveal lipopolysaccharide translocation steps across the Escherichia coli outer membrane

Lipopolysaccharide (LPS) is a main component of the outer membrane of Gram-negative bacteria, which is essential for the vitality of most Gram-negative bacteria and plays a critical role for drug resistance. LptD/E complex forms a N-terminal LPS transport slide, a hydrophobic intramembrane hole and the hydrophilic channel of the barrel, for LPS transport, lipid A insertion and core oligosaccharide and O-antigen polysaccharide translocation, respectively. However, there is no direct evidence to confirm that LptD/E transports LPS from the periplasm to the external leaflet of the outer membrane. By replacing LptD residues with an unnatural amino acid p-benzoyl-L-phenyalanine (pBPA) and UV-photo-cross-linking in E.coli, the translocon and LPS intermediates were obtained at the N-terminal domain, the intramembrane hole, the lumenal gate, the lumen of LptD channel, and the extracellular loop 1 and 4, providing the first direct evidence and “snapshots” to reveal LPS translocation steps across the outer membrane