The plant circadian clock allows organisms to anticipate the predictable changes in the environment by adjusting their developmental and physiological traits. In the last few years, it was determined ...that responses known to be regulated by the oscillator are also able to modulate clock performance. These feedback loops and their multilayer communications create a complex web, and confer on the clock network a role that exceeds the measurement of time. In this article, we discuss the current knowledge of the wiring of the clock, including the interplay with metabolism, hormone, and stress pathways in the model species Arabidopsis thaliana We outline the importance of this system in crop agricultural traits, highlighting the identification of natural alleles that alter the pace of the timekeeper. We report evidence supporting the understanding of the circadian clock as a master regulator of plant life, and we hypothesize on its relevant role in the adaptability to the environment and the impact on the fitness of most organisms.
Circadian clocks allow organisms to anticipate daily changes in the environment to enhance overall fitness. Transcription factors (TFs) play a prominent role in the molecular mechanism but are ...incompletely described possibly due to functional redundancy, gene family proliferation, and/or lack of context-specific assays. To overcome these, we performed a high-throughput yeast one-hybrid screen using the LUX ARRYHTHMO (LUX) gene promoter as bait against an Arabidopsis TF library. LUX is a unique gene because its mutation causes severe clock defects and transcript maintains high-amplitude cycling in the cold. We report the well-characterized cold-inducible C-repeat (CRT)/drought-responsive element (DRE) binding factor CBF1/DREB1b is a transcriptional regulator of LUX. We show that CBF1 binds the CRT in the LUX promoter, and both genes overlap in temporal and spatial expression. CBF1 overexpression causes upregulation of LUX and also alters other clock gene transcripts. LUX promoter regions including the CRT and Evening Element (EE) are sufficient for high-amplitude transcriptional cycling in the cold, and cold-acclimated lux seedlings are sensitive to freezing stress. Our data show cold signaling is integrated into the clock by CBF-mediated regulation of LUX expression, thereby defining a new transcriptional mechanism for temperature input to the circadian clock.
•The LUX clock gene promoter is bound by the cold-induced CBF1 transcription factor•CBF1 overexpression upregulates LUX and alters other clock gene transcripts•The CRT and EE motifs are sufficient to confer evening-phased expression in the cold•lux mutants are sensitive to freezing after cold acclimation
Chow et al. describe how the Arabidopsis circadian clock senses cold. Using genomics, genetics, and biochemistry, they show the cold-inducible transcription factor CBF1 directly regulates the clock gene LUX, which is required for cold-acclimated freezing tolerance. This highlights the importance of transcription for cold perception by the clock.
Light signaling pathways and the circadian clock interact to help organisms synchronize physiological and developmental processes with periodic environmental cycles. The plant photoreceptors ...responsible for clock resetting have been characterized, but signaling components that link the photoreceptors to the clock remain to be identified. Here we describe a family of night light–inducible and clock-regulated genes (LNK) that play a key role linking light regulation of gene expression to the control of daily and seasonal rhythms in Arabidopsis thaliana . A genomewide transcriptome analysis revealed that most light-induced genes respond more strongly to light during the subjective day, which is consistent with the diurnal nature of most physiological processes in plants. However, a handful of genes, including the homologous genes LNK1 and LNK2, are more strongly induced by light in the middle of the night, when the clock is most responsive to this signal. Further analysis revealed that the morning phased LNK1 and LNK2 genes control circadian rhythms, photomorphogenic responses, and photoperiodic dependent flowering, most likely by regulating a subset of clock and flowering time genes in the afternoon. LNK1 and LNK2 themselves are directly repressed by members of the TIMING OF CAB1 EXPRESSION / PSEUDO RESPONSE REGULATOR family of core-clock genes in the afternoon and early night. Thus, LNK1 and LNK2 integrate early light signals with temporal information provided by core oscillator components to control the expression of afternoon genes, allowing plants to keep track of seasonal changes in day length.
Loss to follow-up after traumatic injury occurs at rates of up to 47%. However, the most recent data are over a decade old, and recent changes in traumatic injury patterns necessitate an updated ...assessment of risk factors for loss to follow-up after trauma.
We conducted a retrospective chart review of trauma admissions from January 1, 2018 to December 31, 2021. Categorical variables were compared using χ2 analyses, and continuous variables were analyzed using Mann–Whitney Wilcoxon tests. Multivariable logistic regression was used to adjust for relevant factors identified on unadjusted analysis.
Among 3,034 patients, overall loss to follow-up was 36.9%. Non-White patients, patients who underwent operations or non-surgical procedures, and patients discharged to rehabilitation facilities were more likely to have follow-up appointments within 30 days. Patients with substance use disorder and, among White patients, those with public insurance had higher loss to follow-up rates. Having a follow-up appointment scheduled with a primary care provider was the single most significant factor associated with attending a follow-up appointment.
Social determinants of health, such as insurance status and substance use disorder, are associated with loss of follow-up after trauma. Primary care appointments are associated with the highest attendance rates, supporting that all patients should be offered primary care appointments after traumatic injury.
The Aux/IAA proteins are auxin-sensitive repressors that mediate diverse physiological and developmental processes in plants 1, 2. There are 29 Aux/IAA genes in Arabidopsis that exhibit unique but ...partially overlapping patterns of expression 3. Although some studies have suggested that individual Aux/IAA genes have specialized function, genetic analyses of the family have been limited by the scarcity of loss-of-function phenotypes 4. Furthermore, with a few exceptions, our knowledge of the factors that regulate Aux/IAA expression is limited 1, 5. We hypothesize that transcriptional control of Aux/IAA genes plays a central role in the establishment of the auxin-signaling pathways that regulate organogenesis, growth, and environmental response. Here, we describe a screen for transcription factors (TFs) that regulate the Aux/IAA genes. We identify TFs from 38 families, including 26 members of the DREB/CBF family. Several DREB/CBF TFs directly promote transcription of the IAA5 and IAA19 genes in response to abiotic stress. Recessive mutations in these IAA genes result in decreased tolerance to stress conditions, demonstrating a role for auxin in abiotic stress. Our results demonstrate that stress pathways interact with the auxin gene regulatory network (GRN) through transcription of the Aux/IAA genes. We propose that the Aux/IAA genes function as hubs that integrate genetic and environmental information to achieve the appropriate developmental or physiological outcome.
•The Aux/IAA genes of Arabidopsis are regulated by diverse TFs•The Aux/IAAs function as hubs that integrate signals from diverse pathways•The CBF1 and DREB2A TFs directly regulate two Aux/IAA genes, IAA5 and IAA19•IAA5, IAA6, and IAA19 are required for stress tolerance
The Aux/IAA repressors are key regulators of auxin response in plants, but the factors that regulate their synthesis are largely unknown. Shani et al. identify transcription factors that regulate these genes. The DREB proteins directly regulate expression of IAA5 and IAA19. Furthermore, the authors show that these Aux/IAAs are required for stress tolerance.
IMPORTANCE: Social determinants of health have been shown to be key drivers of disparities in access to surgical care and surgical outcomes. Though the concept of social responsibility has received ...growing attention in the medical field, little has been published contextualizing social responsibility in surgery. In this narrative review, we define social responsibility as it relates to surgery, explore the duty of surgeons to society, and provide examples of social factors associated with adverse surgical outcomes and how they can be mitigated. OBSERVATIONS: The concept of social responsibility in surgery has deep roots in medical codes of ethics and evolved alongside changing views on human rights and the role of social factors in disease. The ethical duty of surgeons to society is based on the ethical principles of benevolence and justice and is grounded within the framework of the social contract. Surgeons have a responsibility to understand how factors such as patient demographics, the social environment, clinician awareness, and the health care system are associated with inequitable patient outcomes. Through education, we can empower surgeons to advocate for their patients, address the causes and consequences of surgical disparities, and incorporate social responsibility into their daily practice. CONCLUSIONS AND RELEVANCE: One of the greatest challenges in the field of surgery is ensuring that surgical care is provided in an equitable and sustainable way. Surgeons have a duty to understand the factors that lead to health care disparities and use their knowledge, skills, and privileged position to address these issues at the individual and societal level.
IMPORTANCE: Some studies based on proportions of patients with perforated appendicitis (PA) among all patients with acute appendicitis (AA) have found an association between socioeconomic status ...(SES) and risk of perforation. A potential limitation is their use of proportions, which assumes that incidence of AA is evenly distributed across populations at risk. This assumption may be invalid, and SES may have a more complex association with both AA and PA. OBJECTIVE: To generate population-based incidences of AA and PA and to examine geographic patterns of incidence alongside geographic patterns of SES. DESIGN, SETTING, AND PARTICIPANTS: Retrospective study of data from Washington’s Comprehensive Hospital Abstract Reporting System and the 2010 US census. Geographic methods were used to identify patterns of age- and sex-standardized incidence in Washington State between 2008 and 2012. The study included all patients discharged with International Classification of Diseases, Ninth Revision codes for AA or PA. Data were analyzed between November 2016 and December 2018. EXPOSURES: Location of primary residence. MAIN OUTCOMES AND MEASURES: Age- and sex-standardized incidence for AA and PA was generated for each census tract (CT). Global spatial autocorrelation was examined using Moran index (0.0 = completely random incidence; 1.0 = fully dependent on location). Clusters of low-incidence CTs (cold spots) and high-incidence CTs (hot spots) were identified for AA. Census-based SES data were aggregated for hot spots and cold spots and then compared. RESULTS: Statewide, over the 5-year study period, there were 35 730 patients with AA (including 9780 cases of PA), of whom 16 574 were women (46.4%). Median age of the cohort was 29 years (IQR, 16-48 years). Statewide incidence of AA and PA was 106 and 29 per 100 000 person-years (PY), respectively. Crude incidence was higher within the male population and peaked at age 10 to 19 years. Age- and sex-standardized incidence of AA demonstrated significant positive spatial autocorrelation (Moran index, 0.30; P < .001), but autocorrelation for PA was only half as strong (0.16; P < .001). Median incidence of AA was 118.1 per 100 000 PY among hot spots vs 86.2 per 100 000 PY among cold spots (P < .001). Socioeconomic status was higher in cold spots vs hot spots: mean proportion of college-educated adults was 56% vs 26% (P < .001), and mean per capita income was $44 691 vs $30 027 (P < .001). CONCLUSIONS AND RELEVANCE: Age- and sex-standardized incidence of appendicitis is not randomly distributed across geographic subunits, and geographic clustering of AA is twice as strong as PA. Socioeconomic advantages, such as higher income and secondary education, are strongly associated with lower incidence of AA. These findings challenge conventional views that AA occurs randomly and has no predisposing characteristics beyond age/sex. Socioeconomic status, and likely other geographically circumscribed factors, are associated with incidence of AA.
Firearm injury remains a major cause of morbidity and mortality in the United States. Because of prior lack of comprehensive data sources, there is a paucity of literature on nonfatal firearm injury. ...Associations have previously been shown between state-level firearm laws and firearm fatalities, but few studies have examined the effects of these laws on nonfatal firearm hospitalization rates. Our objective was to examine the relationship between state firearm laws and firearm injury-related hospitalization rates across all 50 states over a 17-year period.
In this panel study design, we used fixed effects multivariate regression models to analyze the relationship between 12 laws and firearm state-level injury-related hospitalization rates from 2000 to 2016 using the RAND Corporation Inpatient Hospitalizations for Firearm Injury Database. We used difference-in-differences to determine the impact of law passage in a given state compared with those states without the law, controlling for state-level covariates. The main outcome measure was the change in annual firearm injury-related inpatient hospitalization rates after passage or repeal of a state-level firearm law.
Examining each law individually, passage of violent misdemeanor, permitting, firearm removal from domestic violence offenders, and 10-round limit laws were associated with significant firearm injury-related hospitalization rate reductions. Examining multiple laws in the same model, passage of violent misdemeanor laws was associated with a 19.9% (confidence interval, 11.6%-27.4%) reduction, and removal of firearms from domestic violence offenders was associated with a 17.0% (confidence interval, 9.9%-23.6%) reduction in hospitalization rates.
State laws related to preventing violent offenders from possessing firearms are associated with firearm injury-related hospitalization rate reductions. Given significant physical, mental, and social burdens of nonfatal firearm injury, determining the efficacy of firearm-related policy is critical to violence and injury prevention efforts.
Prognostic and Epidemiologic; Level IV.
The purpose of this study was to assess the practice and perceptions of shared decision-making (SDM) by both faculty and residents at Boston Medical Center and explore barriers and facilitators to ...implementing SDM at our institution.
We created and distributed an online survey assessing provider demographic and training characteristics, experiences with the informed consent process, practices in SDM, and perceptions about SDM. We used descriptive statistics to summarize provider characteristics and survey responses and univariate analysis to determine associations between them.
Fifteen surgeons and 19 surgical residents completed the survey (49% response rate). Most respondents were aware of and had a positive attitude toward SDM (91% and 76%, respectively); 35% reported having SDM training. Providers had varying levels of engagement with different SDM practices, and there were inconsistent associations between provider characteristics and the use of SDM. Often providers thought the patient’s health literacy, foreign primary language, clinical condition, and socioeconomic factors were barriers to the SDM process.
Although most general surgery faculty and residents at our institution had a positive view of SDM, they engaged in SDM behaviors inconsistently, with no clear association between clinician characteristics and specific behaviors. We identified several barriers to SDM consistent with those identified by providers in other specialties. This highlights the need for further research to study live general surgery provider-patient interactions, as well as structured SDM education to train general surgery providers to reliably engage their patients in effective SDM.
•We found no consistent association between provider traits and SDM practices.•Providers with SDM knowledge or training were not more likely to practice SDM.•Lower academic rank had the most associations with perceived barriers to SDM.•The most commonly identified barrier to SDM was the patient’s foreign primary language.
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