This paper presents the Adaptive Calibration Model (ACM), an evolutionary-developmental theory of individual differences in the functioning of the stress response system. The stress response system ...has three main biological functions: (1) to coordinate the organism's allostatic response to physical and psychosocial challenges; (2) to encode and filter information about the organism's social and physical environment, mediating the organism's openness to environmental inputs; and (3) to regulate the organism's physiology and behavior in a broad range of fitness-relevant areas including defensive behaviors, competitive risk-taking, learning, attachment, affiliation and reproductive functioning. The information encoded by the system during development feeds back on the long-term calibration of the system itself, resulting in adaptive patterns of responsivity and individual differences in behavior. Drawing on evolutionary life history theory, we build a model of the development of stress responsivity across life stages, describe four prototypical responsivity patterns, and discuss the emergence and meaning of sex differences. The ACM extends the theory of biological sensitivity to context (BSC) and provides an integrative framework for future research in the field.
Background. Enterotoxigenic Bacteroides fragilis (ETBF) produces the Bacteroides fragilis toxin, which has been associated with acute diarrheal disease, inflammatory bowel disease, and colorectal ...cancer (CRC). ETBF induces colon carcinogenesis in experimental models. Previous human studies have demonstrated frequent asymptomatic fecal colonization with ETBF, but no study has investigated mucosal colonization that is expected to impact colon carcinogenesis. Methods. We compared the presence of the bft gene in mucosal samples from colorectal neoplasia patients (cases, n = 49) to a control group undergoing outpatient colonoscopy for CRC screening or diagnostic workup (controls, n = 49). Single bacterial colonies isolated anaerobically from mucosal colon tissue were tested for the bft gene with touch-down polymerase chain reaction. Results. The mucosa of cases was significantly more often bft-positive on left (85.7%) and right (91.7%) tumor and/or paired normal tissues compared with left and right control biopsies (53.1%; P = .033 and 55.5%; P = .04, respectively). Detection of bft was concordant in most paired mucosal samples from individual cases or controls (75% cases; 67% controls). There was a trend toward increased bft positivity in mucosa from late- vs early-stage CRC patients (100% vs 72.7%, respectively; P = .093). In contrast to ETBF diarrheal disease where bft-1 detection dominates, bft-2 was the most frequent toxin isotype identified in both cases and controls, whereas multiple bft isotypes were detected more frequently in cases (P ≤ .02). Conclusions. The bft gene is associated with colorectal neoplasia, especially in late-stage CRC. Our results suggest that mucosal bft exposure is common and may be a risk factor for developing CRC.
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•Crack-free pure molybdenum is fabricated via electron beam melting AM.•Fiber texture switching is observed across various energy density settings.•The weld pool shape likely drives ...the fiber selection mechanism.•Columnar grains consist of fine subgrains believed to be due to process stresses.
Additive manufacturing (AM) technologies offer novel opportunities for processing difficult to cast refractory materials. Electron beam melting (EBM) AM is particularly attractive as the rapidly moving electron beam can be utilized to heat the powder bed which mitigates against some process induced cracking mechanisms. A great deal of prior work has been done to investigate laser based processing of molybdenum but little EBM focused work currently exists. In this work we investigate EBM processed molybdenum and observe sharp 001,111, and mixed 001 &111 crystallographic fibers in the build direction. The apparent preference between these build direction fibers is dependent on the imposed energy density and this is likely explained by the weld pool shape. Detailed microscopy reveals that the observed columnar grains consist of much finer equiaxed low angle boundary subgrains suggesting large process induced stresses leading to appreciable plastic deformation. The implications resulting from this work are that molybdenum may be processed crack-free via EBM AM and that fiber-switching may be controlled, and exploited, towards fabricating components with optimized performance.
Engineered cardiac tissues that can be directly produced from human induced pluripotent stem cells (hiPSCs) in scalable, suspension culture systems are needed to meet the demands of cardiac ...regenerative medicine. Here, we demonstrate successful production of functional cardiac tissue microspheres through direct differentiation of hydrogel encapsulated hiPSCs. To form the microspheres, hiPSCs were suspended within the photocrosslinkable biomaterial, PEG-fibrinogen (25 million cells/mL), and encapsulated at a rate of 420,000 cells/minute using a custom microfluidic system. Even at this high cell density and rapid production rate, high intra-batch and batch-to-batch reproducibility was achieved. Following microsphere formation, hiPSCs maintained high cell viability and continued to grow within and beyond the original PEG-fibrinogen matrix. These initially soft microspheres (<250 Pa) supported efficient cardiac differentiation; spontaneous contractions initiated by differentiation day 8, and the microspheres contained >75% cardiomyocytes (CMs). CMs responded appropriately to pharmacological stimuli and exhibited 1:1 capture up to 6.0 Hz when electrically paced. Over time, cells formed cell-cell junctions and aligned myofibril fibers; engineered cardiac microspheres were maintained in culture over 3 years. The capability to rapidly generate uniform cardiac microsphere tissues is critical for advancing downstream applications including biomanufacturing, multi-well plate drug screening, and injection-based regenerative therapies.
The rate of telomere loss is related to maximum lifespan in birds Tricola, Gianna M.; Simons, Mirre J. P.; Atema, Els ...
Philosophical transactions of the Royal Society of London. Series B. Biological sciences,
03/2018, Volume:
373, Issue:
1741
Journal Article
Peer reviewed
Open access
Telomeres are highly conserved regions of DNA that protect the ends of linear chromosomes. The loss of telomeres can signal an irreversible change to a cell's state, including cellular senescence. ...Senescent cells no longer divide and can damage nearby healthy cells, thus potentially placing them at the crossroads of cancer and ageing. While the epidemiology, cellular and molecular biology of telomeres are well studied, a newer field exploring telomere biology in the context of ecology and evolution is just emerging. With work to date focusing on how telomere shortening relates to individual mortality, less is known about how telomeres relate to ageing rates across species. Here, we investigated telomere length in cross-sectional samples from 19 bird species to determine how rates of telomere loss relate to interspecific variation in maximum lifespan. We found that bird species with longer lifespans lose fewer telomeric repeats each year compared with species with shorter lifespans. In addition, phylogenetic analysis revealed that the rate of telomere loss is evolutionarily conserved within bird families. This suggests that the physiological causes of telomere shortening, or the ability to maintain telomeres, are features that may be responsible for, or co-evolved with, different lifespans observed across species.
This article is part of the theme issue ‘Understanding diversity in telomere dynamics'.
ABSTRACT PURPOSE Lower continuity of care has been associated with higher rates of adverse outcomes for persons with multiple chronic medical conditions. It is unclear, however, whether this ...relationship also exists within integrated systems that offer high levels of informational continuity through shared electronic health records. METHODS We conducted a retrospective cohort study of 12,200 seniors with 3 or more chronic conditions within an integrated delivery system. Continuity of care was calculated using the Continuity of Care Index, which reflects visit concentration with individual clinicians. Using Cox proportional hazards regression permitting continuity to vary monthly until the outcome or censoring event, we separately assessed inpatient admissions and emergency department visits as a function of primary care continuity and specialty care continuity. RESULTS After adjusting for covariates (demographics; baseline, primary, and specialty care visits; baseline outcomes; and morbidity burden), greater primary care continuity and greater specialty care continuity were each associated with a lower risk of inpatient admission (respective hazard ratios (95% CIs) = 0.97 (0.96, 0.99) and 0.95 (0.93, 0.98)) and a lower risk of emergency department visits (respective hazard ratios = 0.97 (0.96, 0.98) and 0.98 (0.96, 1.00)). For the subgroup with 3 or more primary care and 3 or more specialty care visits, specialty care continuity (but not primary care continuity) was independently associated with a decreased risk of inpatient admissions (hazard ratio = 0.94 (0.92, 0.97)), and primary care continuity (but not specialty care continuity) was associated with a decreased risk of emergency department visits (hazard ratio = 0.98 (0.96, 1.00)). CONCLUSIONS In an integrated delivery system with high informational continuity, greater continuity of care is independently associated with lower hospital utilization for seniors with multiple chronic medical conditions. Different subgroups of patients will benefit from continuity with primary and specialty care clinicians depending on their care needs.
Guided by evolutionary-developmental theories of biological sensitivity to context and reproductive development, the current research examined the interactive effects of early family environments and ...psychobiologic reactivity to stress on the subsequent timing and tempo of puberty. As predicted by the theory, among children displaying heightened biological sensitivity to context (i.e., higher stress reactivity), higher quality parent-child relationships forecast slower initial pubertal tempo and later pubertal timing, whereas lower quality parent-child relationships forecast the opposite pattern. No such effects emerged among less context-sensitive children. Whereas sympathetic nervous system reactivity moderated the effects of parent-child relationships on both breast/genital and pubic hair development, adrenocortical activation only moderated the effect on pubic hair development. The current results build on previous research documenting what family contexts predict variation in pubertal timing by demonstrating for whom those contexts matter. In addition, the authors advance a new methodological approach for assessing pubertal tempo using piecewise growth curve analysis.
An estimated 1.4 million persons in the United States identify as transgender or nonbinary, signifying that their gender identity does not correspond with their assigned sex at birth. Individuals ...assigned female at birth may seek gender-affirming hormone therapy with testosterone. No studies have directly examined ovulatory function in transmasculine individuals using injectable testosterone.
Our primary objective was to determine the effect of testosterone on ovulatory suppression in transmasculine individuals. Secondary objectives were to determine predictors of ovulation in transmasculine individuals on testosterone, and to assess the effect of testosterone on antimüllerian hormone.
This prospective observational study recruited participants from a community clinic that provides gender-affirming hormone therapy. Enrolled individuals were assigned female at birth and were currently using or seeking to initiate masculinizing therapy with injectable testosterone esters (transmasculine individuals). Over a 12-week study period, participants collected daily urine samples for pregnanediol-3-glucoronide testing and completed daily electronic bleeding diaries. We assessed monthly serum mid-dosing interval testosterone, estradiol and sex hormone binding globulin, and antimüllerian hormone values at baseline and study end. Ovulation was defined as pregnanediol-3-glucoronide greater than 5 μg/mL for 3 consecutive days. The primary outcome was the proportion of participants who ovulated during the study period. We examined predictors of ovulation such as age, length of time on testosterone, serum testosterone levels, body mass index, and bleeding pattern.
From July to November 2018, we enrolled 32 individuals; 20 completed the study (14 continuing testosterone users, 6 new users). Median age was 23 years (range 18−37 years). Bleeding or spotting during the study period was noted by 41% of participants (13/32). Among continuing users, median testosterone therapy duration was 11 months (range 1−60 months). A single ovulation was observed out of a total of 61 combined months of testosterone use; however, several transient rises in pregnanediol-3-glucoronide followed by bleeding episodes were suggestive of 7 dysfunctional ovulatory cycles among 7 individuals. There was no difference in antimüllerian hormone from baseline to 12 weeks between participants initiating testosterone and continuing users of testosterone. We did not have the power to examine our intended predictors given the low numbers of ovulatory events, but found that longer time on testosterone and presence of vaginal bleeding over 12 weeks were associated with transient rises in pregnanediol-3-glucoronide.
This study suggests that testosterone rapidly induces hypothalamic−pituitary−gonadal suppression, resulting in anovulation in a proportion of new users. Importantly, these data also suggest that some long-term testosterone users break through the hormonal suppression and experience an ovulatory event, thereby raising concerns pertaining to the need for contraception in transmasculine individuals engaged in sexual intercourse with sperm-producing partners. Given the small number of overall participants, this work is hypothesis generating. Larger studies are needed to confirm and to clarify these findings.
The U.S. Preventive Services Task Force (USPSTF) issues “Insufficient Evidence” (I) statements when scientific evidence is inadequate for making recommendations about clinical preventive services. ...Insufficient Evidence statements may be changed to definitive recommendations if new research closes evidence gaps. This study examines the characteristics of evidence that informed changes from I statements to definitive recommendations, including NIH's role as a funder.
A total of 11 USPSTF Insufficient Evidence statements that were changed between 2010 and 2019 were assessed. Study designs, bibliometric influence, and funding sources for scientific articles cited in USPSTF evidence reviews were characterized for each I statement. Data were analyzed in 2019–2020.
Most I statements (82%) changed to a B grade; an average of 8.4 years elapsed between issuing the I statement and releasing the definitive recommendation. An average of 63 (range=19−253) articles were included in each USPSTF evidence review. NIH support was cited in 28.8% of articles, on average. The proportion of NIH-funded articles reporting RCT designs was similar to that of non–NIH-funded articles (64.5% vs 59.5%). A higher proportion of NIH-funded articles were rated good quality for study design (39.0%) than the proportion of non–NIH-funded articles (24.4%). Bibliometric influence measured by relative citation ratios was higher for NIH-funded (mean=14.78) than for non–NIH-funded (mean=5.07) articles.
Study designs and funding supports varied widely across topics, but overall, NIH was the largest single funder of evidence informing 11 changed USPSTF I statements. Enhanced efforts by NIH and other stakeholders to address I statement evidence gaps are needed.
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