Background and Aims
Limited information exists regarding individual subgroups of recovery from opioid use disorder (OUD) following treatment and how these subgroups may relate to recovery ...trajectories. We used multi‐dimensional criteria to identify OUD recovery subgroups and longitudinal transitions across subgroups.
Design, Setting and Participants
In a national longitudinal observational study in the United States, individuals who previously participated in a clinical trial for subcutaneous buprenorphine injections for treatment of OUD were enrolled and followed for an average of 4.2 years after participation in the clinical trial.
Measurements
We identified recovery subgroups based on psychosocial outcomes including depression, opioid withdrawal and pain. We compared opioid use, treatment utilization and quality of life among these subgroups.
Findings
Three dimensions of the recovery process were identified: depression, opioid withdrawal and pain. Using these three dimensions, participants were classified into four recovery subgroups: high‐functioning (minimal depression, mild withdrawal and no/mild pain), pain/physical health (minimal depression, mild withdrawal and moderate pain), depression (moderate depression, mild withdrawal and mild/moderate pain) and low‐functioning (moderate/severe withdrawal, moderate depression and moderate/severe pain). Significant differences among subgroups were observed for DSM‐5 criteria (P < 0.001) and remission status (P < 0.001), as well as with opioid use (P < 0.001), treatment utilization (P < 0.001) and quality of life domains (physical health, psychological, environment and social relationships; Ps < 0.001, Cohen’s fs ≥ 0.62). Recovery subgroup assignments were dynamic, with individuals transitioning across subgroups during the observational period. Moreover, the initial recovery subgroup assignment was minimally predictive of long‐term outcomes.
Conclusions
There appear to be four distinct subgroups among individuals in recovery from OUD. Recovery subgroup assignments are dynamic and predictive of contemporaneous, but not long‐term, substance use, substance use treatment utilization or quality of life outcomes.
Early or late pubertal onset affects up to 5% of adolescents and is associated with adverse health and psychosocial outcomes. Self‐limited delayed puberty (DP) segregates predominantly in an ...autosomal dominant pattern, but the underlying genetic background is unknown. Using exome and candidate gene sequencing, we have identified rare mutations in IGSF10 in 6 unrelated families, which resulted in intracellular retention with failure in the secretion of mutant proteins. IGSF10 mRNA was strongly expressed in embryonic nasal mesenchyme, during gonadotropin‐releasing hormone (GnRH) neuronal migration to the hypothalamus. IGSF10 knockdown caused a reduced migration of immature GnRH neurons in vitro, and perturbed migration and extension of GnRH neurons in a gnrh3:EGFP zebrafish model. Additionally, loss‐of‐function mutations in IGSF10 were identified in hypothalamic amenorrhea patients. Our evidence strongly suggests that mutations in IGSF10 cause DP in humans, and points to a common genetic basis for conditions of functional hypogonadotropic hypogonadism (HH). While dysregulation of GnRH neuronal migration is known to cause permanent HH, this is the first time that this has been demonstrated as a causal mechanism in DP.
Synopsis
Self‐limited delayed puberty (DP) has strong familial inheritance, but the underlying genetic determinants are unknown. IGSF10 deficiency is found to affect embryonic GnRH neuronal migration and results in DP in humans.
Pathogenic mutations in IGSF10 are found in patients with self‐limited delayed puberty.
IGSF10 is a gene of previously unclear function with no known human mutations.
IGSF10 is expressed within the nasal mesenchyme during fetal development, in a pattern similar to known chemokines that direct migrational GnRH neurons to the hypothalamus.
Knockdown of IGSF10 led to a reduced migration of GnRH neurons in vitro and in a transgenic zebrafish model.
IGSF10 loss‐of‐function mutations were also identified in patients with hypothalamic amenorrhea, suggesting an overlapping genetic and mechanistic basis between different types of functional hypogonadotropic hypogonadism, including DP and hypothalamic amenorrhea.
Self‐limited delayed puberty (DP) has strong familial inheritance, but the underlying genetic determinants are unknown. IGSF10 deficiency is found to affect embryonic GnRH neuronal migration and results in DP in humans.
Parastomal hernias are common and many are never repaired. Emergency parastomal hernia repair (PHR) is a feared complication following ostomy creation, yet the incidence and long-term outcomes of ...emergency PHR are unknown.
We performed a retrospective analysis of 100% Medicare claims data (2007-2015) to evaluate complications, readmissions, reoperations, hospitalizations, and mortality after emergency PHR. We used logistic regression and Cox proportional hazard models to determine the association of surgical approach, including repair with ostomy reversal, resiting, mesh, minimally invasive approach, or a myofascial flap. Analysis took place between June 2022 and February 2023.
A total of 6658 patients underwent emergency PHR (mean standard deviation age, 75.9 9.8 y; 4031 female individuals 60.5%). Overall, 3433 (51.2%) patients underwent primary PHR, 1626 (24.4%) underwent PHR with ostomy resiting, and 1599 (24.0%) underwent PHR with ostomy reversal. In the 30 d after surgery, 4151 (62.3%) patients had complications and 55 (0.83%) underwent reoperation. Compared to local repair, the 30-d odds of complications were lower for patients who underwent ostomy resiting (odds ratio 0.82 95% confidence interval 0.72-0.93). Five y after surgery, the cumulative incidence of reoperation was 12.0% and was lowest for patients who underwent PHR with ostomy reversal (hazard ratio 0.15 95% confidence interval 0.11-0.21) when compared to local repair.
Emergency PHR is associated with significant morbidity. However, technique selection may influence outcomes. Understanding the prognosis of emergency PHR may improve decision-making and patient counseling for patients living with this common disease.
Reducing exposure to obesogens is a strategy for preventing obesity.
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•There is an expanding global obesity pandemic.•Ubiquitous environmental chemicals called obesogens play a vital ...role in the obesity pandemic.•Exposure to obesogens occurs throughout the life course from before conception until death.•Development is the most sensitive time for obesogens to impact future weight gain across the lifespan and generations.•Obesogens can act via epigenetic mechanisms.•There is a need to expand understanding of the obesogen paradigm to clinicians and consumers.
Obesity is a multifactorial disease with both genetic and environmental components. The prevailing view is that obesity results from an imbalance between energy intake and expenditure caused by overeating and insufficient exercise. We describe another environmental element that can alter the balance between energy intake and energy expenditure: obesogens. Obesogens are a subset of environmental chemicals that act as endocrine disruptors affecting metabolic endpoints. The obesogen hypothesis posits that exposure to endocrine disruptors and other chemicals can alter the development and function of the adipose tissue, liver, pancreas, gastrointestinal tract, and brain, thus changing the set point for control of metabolism. Obesogens can determine how much food is needed to maintain homeostasis and thereby increase the susceptibility to obesity. The most sensitive time for obesogen action is in utero and early childhood, in part via epigenetic programming that can be transmitted to future generations. This review explores the evidence supporting the obesogen hypothesis and highlights knowledge gaps that have prevented widespread acceptance as a contributor to the obesity pandemic. Critically, the obesogen hypothesis changes the narrative from curing obesity to preventing obesity.
Global Mapping of the Yeast Genetic Interaction Network Amy Hin Yan Tong; Lesage, Guillaume; Bader, Gary D. ...
Science (American Association for the Advancement of Science),
02/2004, Letnik:
303, Številka:
5659
Journal Article
Recenzirano
A genetic interaction network containing ~1000 genes and ~4000 interactions was mapped by crossing mutations in 132 different query genes into a set of ~4700 viable gene yeast deletion mutants and ...scoring the double mutant progeny for fitness defects. Network connectivity was predictive of function because interactions often occurred among functionally related genes, and similar patterns of interactions tended to identify components of the same pathway. The genetic network exhibited dense local neighborhoods; therefore, the position of a gene on a partially mapped network is predictive of other genetic interactions. Because digenic interactions are common in yeast, similar networks may underlie the complex genetics associated with inherited phenotypes in other organisms.
Racial and ethnic discrimination persist in science, technology, engineering and mathematics fields, including ecology, evolution and conservation biology (EECB) and related disciplines. ...Marginalization and oppression as a result of institutional and structural racism continue to create barriers to inclusion for Black people, Indigenous people and people of colour (BIPOC), and remnants of historic racist policies and pseudoscientific theories continue to plague these fields. Many academic EECB departments seek concrete ways to improve the climate and implement anti-racist policies in their teaching, training and research activities. We present a toolkit of evidence-based interventions for academic EECB departments to foster anti-racism in three areas: in the classroom; within research laboratories; and department wide. To spark restorative discussion and action in these areas, we summarize EECB's racist and ethnocentric histories, as well as current systemic problems that marginalize non-white groups. Finally, we present ways that EECB departments can collectively address shortcomings in equity and inclusion by implementing anti-racism, and provide a positive model for other departments and disciplines.
Background
One approach to evaluate decision-making is using the concept of decision regret, which measures patient remorse after a healthcare decision. This is particularly important for elective, ...preference-sensitive conditions with multiple treatment options, such as ventral and inguinal hernia repair. In this study, we assessed decision regret among patients who pursued surgical management of ventral and inguinal hernias.
Methods
We retrospectively reviewed a statewide registry of adult patients who underwent elective ventral and inguinal hernia repair between January 2017 and March 2020 and completed a validated survey measuring decision regret. 30-day outcomes included complications, emergency department (ED) utilization, readmission, and reoperation. Multivariable logistic regression examined the association of regret with age, sex, race, insurance status, ASA, tobacco use, diabetes, admission status, surgical approach (open vs. laparoscopic vs. robotic), year, and outcomes.
Results
8315 patients underwent surgery during the study period with a mean age of 60.5 (14.7) years and 1812 (22%) female patients. Among 2159 patients who underwent ventral hernia repair, 248 (11%) reported regret to undergo surgery, 64 (3%) experienced a complication, 160 (7%) visited an ED, 86 (4%) were readmitted, and 29 (1%) underwent reoperation. Outcomes associated with regret after ventral hernia repair included complications (OR 2.33, 95% CI 1.26–4.29) and readmission (OR 2.67, 95% CI 1.51–4.71). Among 6,156 patients who underwent inguinal hernia repair, 533 (9%) reported regret to undergo surgery, 41 (1%) experienced a complication, 304 (5%) visited an ED, 72 (1%) were readmitted, and 63 (1%) underwent reoperation. Outcomes associated with regret after inguinal hernia repair included ED visits (OR 2.03, 95% CI 1.44–2.87) and readmission (OR 4.23, 95% CI 2.35–7.61).
Conclusion
Roughly 1 in 10 patients undergoing hernia repair report regret with their decision to undergo surgery. Developing a better understanding of the factors associated with decision regret after hernia repair may better inform both patients and surgeon decision-making.
Bacterial vaginosis (BV) is a highly prevalent condition that is associated with adverse health outcomes. It has been proposed that BV's role as a pathogenic condition is mediated via ...bacteria-induced inflammation. However, the complex interplay between vaginal microbes and host immune factors has yet to be clearly elucidated. Here, we develop molBV, a 16 S rRNA gene amplicon-based classification pipeline that generates a molecular score and diagnoses BV with the same accuracy as the current gold standard method (i.e., Nugent score). Using 3 confirmatory cohorts we show that molBV is independent of the 16 S rRNA region and generalizable across populations. We use the score in a cohort without clinical BV states, but with measures of HPV infection history and immune markers, to reveal that BV-associated increases in the IL-1β/IP-10 cytokine ratio directly predicts clearance of incident high-risk HPV infection (HR = 1.86, 95% CI: 1.19-2.9). Furthermore, we identify an alternate inflammatory BV signature characterized by elevated TNF-α/MIP-1β ratio that is prospectively associated with progression of incident infections to CIN2 + (OR = 2.81, 95% CI: 1.62-5.42). Thus, BV is a heterogeneous condition that activates different arms of the immune response, which in turn are independent risk factors for HR-HPV clearance and progression. Clinical Trial registration number: The CVT trial has been registered under: NCT00128661.
Characterizing the capacity of marine organisms to adapt to climate change related drivers (e.g., pCO2 and temperature), and the possible rate of this adaptation, is required to assess their ...resilience (or lack thereof) to these drivers. Several studies have hypothesized that epigenetic markers such as DNA methylation, histone modifications and noncoding RNAs, act as drivers of adaptation in marine organisms, especially corals. However, this hypothesis has not been tested in zooplankton, a keystone organism in marine food webs. The objective of this study is to test the hypothesis that acute ocean acidification (OA) exposure alters DNA methylation in two zooplanktonic species—copepods (Acartia clausii) and cladocerans (Evadne nordmanii). We exposed these two species to near‐future OA conditions (400 and 900 ppm pCO2) for 24 h and assessed transcriptional and DNA methylation patterns using RNA sequencing and Reduced Representation Bisulfite Sequencing (RRBS). OA exposure caused differential expression of genes associated with energy metabolism, cytoskeletal and extracellular matrix functions, hypoxia and one‐carbon metabolism. Similarly, OA exposure also caused altered DNA methylation patterns in both species but the effect of these changes on gene expression and physiological effects remains to be determined. The results from this study form the basis for studies investigating the potential role of epigenetic mechanisms in OA induced phenotypic plasticity and/or adaptive responses in zooplanktonic organisms.
Characterizing the capacity of marine organisms to adapt to climate‐change‐related drivers (e.g. pCO2 and temperature), and the possible rate of this adaptation, is required to assess their resilience (or lack thereof) to these drivers. In an effort to understand these, we conducted a study investigating the potential epigenetic changes in response to Ocean acidification in two planktonic species of ecological importance (Copepod, Acartia clausi and Cladoceran, Evadne nordmanni). Our results suggest that these organisms can employ epigenetic mechanisms in coping with acute changes in pCO2 levels. Future research will characterize long‐term adaptive responses to climatic factors such as pCO2 and temperature.
Changes to the supermarket supply chain in recent decades have “squeezed out” local and small farmers in exchange for more consolidated and global suppliers. As a result, these small-scale farmers ...have turned to more direct-to-consumer markets, which capture a higher price point but also bear higher marketing costs. Previous research indicates potential saturation and lack of profitability in this market type. Researchers have explored strategies for “scaling up” local farmers into intermediary supply chains, such as grocery retail, and have tested the profitability of hybrid marketing strategies with positive results. However, there are very few studies that utilize production costs to test market feasibility, and even fewer that include retailer willingness-to-pay estimates. To assess strategies from the perspectives of both producers and buyers, this study uses salad mix in Southeast Michigan as a pilot case. Farmer-generated production costs incurred for strategies and production types were estimated in focus groups, and retailer willingness-to-pay estimates were obtained in interviews. The analysis suggests that a combination of more efficient harvest technology and central processing would have the greatest impact on increasing profitability, but the dramatic effect that central processing has on output price makes it the most feasible strategy for small-scale farmers. In addition, the minimal costs of organic certification for small farmers are likely to be justified by the price premium that grocery retailers are willing to pay. Hydroponic production may be challenging to break even at a smaller scale but could potentially meet retailers’ price preferences at larger scales. Pairing production cost estimates with buyer willingness-to-pay estimates may generate more comprehensive assessments of the relative profitability of potential scaling-up strategies. This method could be applied to other crops, regions, and produce buyers by cooperative extension, nonprofit, or local government personnel working with small farmers on their market development plans.
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