Therapist-Driven Telephone Call Outreach to Improve Depression Remission in a Federally Qualified Health Center.

The authors examined the feasibility and impact of a therapist-driven outreach program on depression outcomes in a primary care clinic. Patients with a diagnosis of depression but missing a 1-year follow-up Patient Health Questionnaire-9 (PHQ-9) screening were rescreened via telephone. Eligible patients (N=241) were contacted, and implementation rates and outcomes, along with feasibility, were assessed. Of the patients contacted, 47% indicated a depression response (reduction in PHQ-9 score of ≥50%), and 33% met remission criteria (PHQ-9 score <5). PHQ-9 scores decreased by approximately 7 points (p<0.001). This project may have helped to improve depression symptoms and remission rates for patients of the clinic and to facilitate patient reengagement with treatment.

Root canal re-treatment with gutta percha - which techniques influence success?

OBJECTIVE: A systematic review and meta-analysis of the literature was carried out assessing the success rate of root canal retreatment using gutta percha. DATA SOURCES: Four of the largest databases were used to identify existing literature with no date or language restrictions. PubMed, Cochrane, ScienceDirect, Scopus and other additional sources were searched. Grey literature was also reviewed. STUDY SELECTION: Two authors, with Master's degrees in endodontics and with extensive university teaching experience, were selected to screen the databases to identify suitable studies. In case the authors were not able to agree during the study selection process, a third investigator was consulted. Specific inclusion and exclusion criteria were outlined and adhered to in the study selection. Two randomised controlled trials, seven single arm prospective studies and one single arm ambispective study published before the 10th of December 2022 were included. These studies evaluated the success of root canal re-treatment, obturated with gutta percha with at least a 1-year follow-up. Nine of the studies were published between 1998 and 2022. Seven studies were conducted in Europe, one in North America and one in Asia. DATA EXTRACTION AND SYNTHESIS: Standard Cochrane methods to assess interval validity were used. Risk of bias in individual studies was assessed using The Newcastle-Ottawa quality assessment scale (NOS) for single-arm studies, and the Cochrane risk of bias tool (RoB2) was used for randomised controlled trials. Outcome measures were standardised as either success or failure of root canal retreatment. Success was classified into 2 different criteria: Strict criteria = absence of clinical signs and symptoms and radiographically normal periodontal ligament space; and Loose criteria = absence of clinical signs and symptoms and absence or reduction of apical radiolucency in the control radiograph. Statistical analysis was undertaken using R software and the Freeman-Turkey transformation was performed. Results were visualised using forest plots. Heterogeneity between studies was measured using the Cochrane Q test and I2 values. RESULTS: Whilst following strict criteria, the success rate of non-surgical root canal retreatment obturated with gutta percha was 71% for 1-3 years follow-up (95% CI, 0.66-0.77) and 77% for 4-5 years follow-up (95% CI, 0.67-0.86). Heterogeneity was moderate (I2 = 61.4) and low (I2 = 0.0), respectively. Factors reducing the success rate of root canal re-retreatment under the strict criteria were older patients, mandibular teeth, molar teeth, the presence of a peri-apical radiolucency, teeth with a previous radiolucency, large peri-apical radiolucency's, higher initial periapical index scores and multiple visit-retreatments. Following the loose criteria, the success rate of non-surgical root canal re-treatment obturated with gutta percha was 87% for 1-3 years follow-up (95% CI, 0.79-0.93) with significant heterogeneity across the studies (I2 = 88.5%). Factors influencing the success rate under the loose criteria were large periapical lesions >5 mm and higher initial periapical index (PAI) scores. CONCLUSIONS: Non-surgical root canal retreatment results in favourable outcomes. However, there are several factors which can result in a lower success rate: the presence and size of a periapical radiolucency, a higher initial PAI score, multiple-visit retreatments, and the size and position of the tooth.

Long-Term Survival Rates and Treatment Trends of Burkitt Lymphoma in Patients with HIV-A National Cancer Database (NCDB) Study.

BACKGROUND: Burkitt lymphoma (BL) accounts for 10-35% of AIDS-defining lymphoma in people with HIV (PWH). Previous research consisting of smaller cohorts has shown decreased survival for HIV-associated BL. This study aims to compare overall mortality in BL patients with and without HIV, while investigating impact of treatment modalities in HIV-associated BL. METHODS: Using the 2004-2019 NCDB, we identified 4312 patients with stage 3 or 4 BL who had a known HIV status and received either chemotherapy alone or chemotherapy and immunotherapy. Time to death was evaluated using Kaplan-Meier survival estimates. Risk of death was evaluated using an extended multivariable Cox model adjusted for multiple factors and with a Heaviside function for HIV status by time period (0-3 month vs. 3-60 month). RESULTS: Of the 4312 patients included, 1514 (35%) had HIV. For months 0-3 from time of diagnosis, HIV status was not associated with a statistically significant increase in risk of death (HR = 1.04, 95% CI: 0.86, 1.26, p = 0.6648). From month 3to 60, positive HIV status was associated with a 55% increase in risk of death compared to those without HIV (95% CI: 1.38, 1.75, p < 0.0001). Further, this difference in hazard rates (0-3 vs. 3-60) was statistically significant (HR = 1.49, 95% CI: 1.22-1.82, p < 0.001). CONCLUSIONS: There is an increased mortality rate from months 3 to 60 in BL patients with HIV compared to patients without HIV. Additionally, risk of death in the first 3 months is significantly decreased by 45% in patients with HIV treated with combination chemotherapy and immunotherapy compared to patients without HIV receiving combination chemotherapy and immunotherapy, providing valuable clinical insight into treatment decision making in the care of HIV-associated BL.

Anesthetic Management for Cesarean Delivery in a Patient With a Difficult Airway and Risks for Postpartum Hemorrhage: A Case Report.

Neuraxial anesthesia is the preferred anesthesia technique for cesarean delivery, however, conversion to general anesthesia may be required for a variety of clinical scenarios, including massive post-partum hemorrhage. Obstetric patients are known to have otherwise more difficult airways and emergent situations can increase the likelihood of failed intubation with potentially disastrous consequences. We describe a novel anesthesia technique for cesarean delivery using neuraxial anesthesia as the primary anesthetic technique and electively securing the airway for a patient with multiple risk factors for post-partum hemorrhage and features concerning difficult intubation.

The Transcriptomic Signature of Cyclical Parthenogenesis.

Cyclical parthenogenesis, where females can engage in sexual or asexual reproduction depending on environmental conditions, represents a novel reproductive phenotype that emerged during eukaryotic evolution. The fact that environmental conditions can trigger cyclical parthenogens to engage in distinct reproductive modes strongly suggests that gene expression plays a key role in the origin of cyclical parthenogenesis. However, the genetic basis underlying cyclical parthenogenesis remains understudied. In this study, we characterize the female transcriptomic signature of sexual versus asexual reproduction in the cyclically parthenogenetic microcrustacean Daphnia pulex and Daphnia pulicaria. Our analyses of differentially expressed genes (DEGs), pathway enrichment, and gene ontology (GO) term enrichment clearly show that compared with sexual reproduction, the asexual reproductive stage is characterized by both the underregulation of meiosis and cell cycle genes and the upregulation of metabolic genes. The consensus set of DEGs that this study identifies within the meiotic, cell cycle, and metabolic pathways serves as candidate genes for future studies investigating how the two reproductive cycles in cyclical parthenogenesis are mediated at a molecular level. Furthermore, our analyses identify some cases of divergent expression among gene family members (e.g., doublesex and NOTCH2) associated with asexual or sexual reproductive stage, suggesting potential functional divergence among gene family members.

Serotonin transporter (5-HTT) gene network moderates the impact of prenatal maternal adversity on orbitofrontal cortical thickness in middle childhood.

In utero, the developing brain is highly susceptible to the environment. For example, adverse maternal experiences during the prenatal period are associated with outcomes such as altered neurodevelopment and emotion dysregulation. Yet, the underlying biological mechanisms remain unclear. Here, we investigate whether the function of a network of genes co-expressed with the serotonin transporter in the amygdala moderates the impact of prenatal maternal adversity on the structure of the orbitofrontal cortex (OFC) in middle childhood and/or the degree of temperamental inhibition exhibited in toddlerhood. T1-weighted structural MRI scans were acquired from children aged 6-12 years. A cumulative maternal adversity score was used to conceptualize prenatal adversity and a co-expression based polygenic risk score (ePRS) was generated. Behavioural inhibition at 18 months was assessed using the Early Childhood Behaviour Questionnaire (ECBQ). Our results indicate that in the presence of a low functioning serotonin transporter gene network in the amygdala, higher levels of prenatal adversity are associated with greater right OFC thickness at 6-12 years old. The interaction also predicts temperamental inhibition at 18 months. Ultimately, we identified important biological processes and structural modifications that may underlie the link between early adversity and future deviations in cognitive, behavioural, and emotional development.

Examining resting-state network connectivity in children exposed to perinatal maternal adversity using anatomically weighted functional connectivity (awFC) analyses; A preliminary report.

Introduction: Environmental perturbations during critical periods can have pervasive, organizational effects on neurodevelopment. To date, the literature examining the long-term impact of early life adversity has largely investigated structural and functional imaging data outcomes independently. However, emerging research points to a relationship between functional connectivity and the brain's underlying structural architecture. For instance, functional connectivity can be mediated by the presence of direct or indirect anatomical pathways. Such evidence warrants the use of structural and functional imaging in tandem to study network maturation. Accordingly, this study examines the impact of poor maternal mental health and socioeconomic context during the perinatal period on network connectivity in middle childhood using an anatomically weighted functional connectivity (awFC) approach. awFC is a statistical model that identifies neural networks by incorporating information from both structural and functional imaging data. Methods: Resting-state fMRI and DTI scans were acquired from children aged 7-9 years old. Results: Our results indicate that maternal adversity during the perinatal period can affect offspring's resting-state network connectivity during middle childhood. Specifically, in comparison to controls, children of mothers who had poor perinatal maternal mental health and/or low socioeconomic status exhibited greater awFC in the ventral attention network. Discussion: These group differences were discussed in terms of the role this network plays in attention processing and maturational changes that may accompany the consolidation of a more adult-like functional cortical organization. Furthermore, our results suggest that there is value in using an awFC approach as it may be more sensitive in highlighting connectivity differences in developmental networks associated with higher-order cognitive and emotional processing, as compared to stand-alone FC or SC analyses.

Mycophenolate Mofetil for Systemic Lupus Erythematosus: Our 20-Year Experience.

OBJECTIVES: Mycophenolate mofetil (MMF) has been long used in the treatment of systemic lupus erythematosus (SLE). Further studies are warranted to investigate its long-term use in maintenance treatment of lupus nephritis (LN). The purpose of this study was to describe our practice experience using MMF with regard to its indications, safety, tolerability, and treatment efficacy. We sought to identify rates of renal remission, flare and progression to end-stage renal disease (ESRD). METHODS: In this retrospective chart review, we identified all patients treated with MMF between 1999 and 2019. Descriptive statistics were used to identify occurrence of remission, occurrence of flares, progression to ESRD, and occurrence of adverse effects. RESULTS: One hundred and one patients were treated with MMF for a mean duration of 69 months. The most common indication was LN (90%). Among patients with LN, 60% achieved complete remission and 16% achieved partial remission at one-year follow-up. Ten patients flared while on maintenance therapy and seven patients flared after treatment was discontinued. Of the 40 patients who were treated for at least five years, one patient developed a flare. Of the 13 patients who were treated for at least 10 years, none developed a flare. One patient on maintenance therapy progressed to ESRD. The most common adverse effects were leukopenia (9%), nausea (7%) and diarrhea (6%). CONCLUSION: Maintenance treatment with MMF constitutes an effective long-term treatment for lupus nephritis. Our practice demonstrates its tolerability over many years with few adverse effects, prevention of renal flares, and a low progression rate to ESRD.

The Mediator complex subunit MED25 interacts with HDA9 and PIF4 to regulate thermomorphogenesis.

Thermomorphogenesis is, among other traits, characterized by enhanced hypocotyl elongation due to the induction of auxin biosynthesis genes like YUCCA8 by transcription factors, most notably PHYTOCHROME INTERACTING FACTOR 4 (PIF4). Efficient binding of PIF4 to the YUCCA8 locus under warmth depends on HISTONE DEACETYLASE 9 (HDA9) activity, which mediates histone H2A.Z depletion at the YUCCA8 locus. However, HDA9 lacks intrinsic DNA-binding capacity, and how HDA9 is recruited to YUCCA8, and possibly other PIF4-target sites, is currently not well understood. The Mediator complex functions as a bridge between transcription factors bound to specific promoter sequences and the basal transcription machinery containing RNA polymerase II. Mutants of Mediator component Mediator25 (MED25) exhibit reduced hypocotyl elongation and reduced expression of YUCCA8 at 27°C. In line with a proposed role for MED25 in thermomorphogenesis in Arabidopsis (Arabidopsis thaliana), we demonstrated an enhanced association of MED25 to the YUCCA8 locus under warmth and interaction of MED25 with both PIF4 and HDA9. Genetic analysis confirmed that MED25 and HDA9 operate in the same pathway. Intriguingly, we also showed that MED25 destabilizes HDA9 protein. Based on our findings, we propose that MED25 recruits HDA9 to the YUCCA8 locus by binding to both PIF4 and HDA9.

Mitochondrial network configuration influences sarcomere and myosin filament structure in striated muscles.

Sustained muscle contraction occurs through interactions between actin and myosin filaments within sarcomeres and requires a constant supply of adenosine triphosphate (ATP) from nearby mitochondria. However, it remains unclear how different physical configurations between sarcomeres and mitochondria alter the energetic support for contractile function. Here, we show that sarcomere cross-sectional area (CSA) varies along its length in a cell type-dependent manner where the reduction in Z-disk CSA relative to the sarcomere center is closely coordinated with mitochondrial network configuration in flies, mice, and humans. Further, we find myosin filaments near the sarcomere periphery are curved relative to interior filaments with greater curvature for filaments near mitochondria compared to sarcoplasmic reticulum. Finally, we demonstrate variable myosin filament lattice spacing between filament ends and filament centers in a cell type-dependent manner. These data suggest both sarcomere structure and myofilament interactions are influenced by the location and orientation of mitochondria within muscle cells.

Fluorescence-estimated oil concentration (Foil) in the Deepwater Horizon subsea oil plume.

Tracking the subsea oil plume during the 2010 Deepwater Horizon Oil Spill (DWH) was conducted using in situ fluorescence via vertical profilers (n = 1157) and discrete sample chemical analyses (n = 7665). During monitoring efforts, discrete samples provided a coarse picture of the oil plume footprint, but the majority of the samples were below standard analytical detection limits for petroleum hydrocarbons. In situ fluorescence data improved the spatial and temporal resolution of the subsea oil plume characterization. Here we synthesized millions of continuous fluorescence data points from hundreds of contemporaneously discrete samples collected to demonstrate how fluorescence could serve as a proxy for Benzene-Toluene-Ethylbenzene-Xylene (BTEX) concentration. Data mined from Gulf Science Data repository were well correlated, and geographically and temporally aligned to provide direct comparisons. Described here are the methods used to calibrate the fluorescence data and to spatially approximate the three-dimensional geographic extent of the oil plume.

A tRNA-Acetylating Toxin and Detoxifying Enzyme in Mycobacterium tuberculosis.

Toxin-antitoxin (TA) systems allow bacteria to adapt to changing environments without altering gene expression. Despite being overrepresented in Mycobacterium tuberculosis, their physiological roles remain elusive. We describe a TA system in M. tuberculosis which we named TacAT due to its homology to previously discovered systems in Salmonella. The toxin, TacT, blocks growth by acetylating glycyl-tRNAs and inhibiting translation. Its effects are reversed by the enzyme peptidyl tRNA hydrolase (Pth), which also cleaves peptidyl tRNAs that are prematurely released from stalled ribosomes. Pth is essential in most bacteria and thereby has been proposed as a promising drug target for complex pathogens like M. tuberculosis. Transposon sequencing data suggest that the tacAT operon is nonessential for M. tuberculosis growth in vitro, and premature stop mutations in this TA system present in some clinical isolates suggest that it is also dispensable in vivo. We assessed whether TacT modulates pth essentiality in M. tuberculosis because drugs targeting Pth might prompt resistance if TacAT is disrupted. We show that pth essentiality is unaffected by the absence of tacAT. These results highlight a fundamental aspect of mycobacterial biology and indicate that Pth's essential role hinges on its peptidyl-tRNA hydrolase activity. Our work underscores Pth's potential as a viable target for new antibiotics. IMPORTANCE The global rise in antibiotic-resistant tuberculosis has prompted an urgent search for new drugs. Toxin-antitoxin (TA) systems allow bacteria to adapt rapidly to environmental changes, and Mycobacterium tuberculosis encodes more TA systems than any known pathogen. We have characterized a new TA system in M. tuberculosis: the toxin, TacT, acetylates charged tRNA to block protein synthesis. TacT's effects are reversed by the essential bacterial enzyme peptidyl tRNA hydrolase (Pth), which is currently being explored as an antibiotic target. Pth also cleaves peptidyl tRNAs that are prematurely released from stalled ribosomes. We assessed whether TacT modulates pth essentiality in M. tuberculosis because drugs targeting Pth might prompt resistance if TacT is disrupted. We show that pth essentiality is unaffected by the absence of this TA system, indicating that Pth's essential role hinges on its peptidyl-tRNA hydrolase activity. Our work underscores Pth's potential as a viable target for new antibiotics.

GNAT toxins evolve toward narrow tRNA target specificities.

Type II toxin-antitoxin (TA) systems are two-gene modules widely distributed among prokaryotes. GNAT toxins associated with the DUF1778 antitoxins represent a large family of type II TAs. GNAT toxins inhibit cell growth by disrupting translation via acetylation of aminoacyl-tRNAs. In this work, we explored the evolutionary trajectory of GNAT toxins. Using LC/MS detection of acetylated aminoacyl-tRNAs combined with ribosome profiling, we systematically investigated the in vivo substrate specificity of an array of diverse GNAT toxins. Our functional data show that the majority of GNAT toxins are specific to Gly-tRNA isoacceptors. However, the phylogenetic analysis shows that the ancestor of GNAT toxins was likely a relaxed specificity enzyme capable of acetylating multiple elongator tRNAs. Together, our data provide a remarkable snapshot of the evolution of substrate specificity.

Parthenogenesis doubles the rate of amino acid substitution in whiptail mitochondria.

Sexual reproduction is ubiquitous in the natural world, suggesting that sex must have extensive benefits to overcome the cost of males compared to asexual reproduction. One hypothesized advantage of sex with strong theoretical support is that sex plays a role in removing deleterious mutations from the genome. Theory predicts that transitions to asexuality should lead to the suppression of recombination and segregation and, in turn, weakened natural selection, allowing for the accumulation of slightly deleterious mutations. We tested this prediction by estimating the dN/dS ratios in asexual vertebrate lineages in the genus Aspidoscelis using whole mitochondrial genomes from seven asexual and five sexual species. We found higher dN/dS ratios in asexual Aspidoscelis species, indicating that asexual whiptails accumulate nonsynonymous substitutions due to weaker purifying selection. Additionally, we estimated nucleotide diversity and found that asexuals harbor significantly less diversity. Thus, despite their recent origins, slightly deleterious mutations accumulated rapidly enough in asexual lineages to be detected. We provide empirical evidence to corroborate the connection between asexuality and increased amino acid substitutions in asexual vertebrate lineages.

Warming increased bark beetle-induced tree mortality by 30% during an extreme drought in California.

Quantifying the responses of forest disturbances to climate warming is critical to our understanding of carbon cycles and energy balances of the Earth system. The impact of warming on bark beetle outbreaks is complex as multiple drivers of these events may respond differently to warming. Using a novel model of bark beetle biology and host tree interactions, we assessed how contemporary warming affected western pine beetle (Dendroctonus brevicomis) populations and mortality of its host, ponderosa pine (Pinus ponderosa), during an extreme drought in the Sierra Nevada, California, United States. When compared with the field data, our model captured the western pine beetle flight timing and rates of ponderosa pine mortality observed during the drought. In assessing the influence of temperature on western pine beetles, we found that contemporary warming increased the development rate of the western pine beetle and decreased the overwinter mortality rate of western pine beetle larvae leading to increased population growth during periods of lowered tree defense. We attribute a 29.9% (95% CI: 29.4%-30.2%) increase in ponderosa pine mortality during drought directly to increases in western pine beetle voltinism (i.e., associated with increased development rates of western pine beetle) and, to a much lesser extent, reductions in overwintering mortality. These findings, along with other studies, suggest each degree (°C) increase in temperature may have increased the number of ponderosa pine killed by upwards of 35%-40% °C-1 if the effects of compromised tree defenses (15%-20%) and increased western pine beetle populations (20%) are additive. Due to the warming ability to considerably increase mortality through the mechanism of bark beetle populations, models need to consider climate's influence on both host tree stress and the bark beetle population dynamics when determining future levels of tree mortality.

Biliary-Caval Fistula following Y90 Radioembolization.

The safety of radioembolization with yttrium-90 ( 90 Y) is well documented and major complications are rare. Previous studies have demonstrated that biliary complications following 90 Y, including bile duct injury and hepatic abscess formation, occur at an increased rate in patients who have had prior biliary surgery and interventions. This article reviews a case of a patient who developed recurrent cholangitis and sepsis as well as a biliary-caval fistula following radioembolization. Additionally, we review current data regarding biliary complications following radioembolization in patients with prior biliary intervention.

Auxiliary interfaces support the evolution of specific toxin-antitoxin pairing.

Toxin-antitoxin (TA) systems are a large family of genes implicated in the regulation of bacterial growth and its arrest in response to attacks. These systems encode nonsecreted toxins and antitoxins that specifically pair, even when present in several paralogous copies per genome. Salmonella enterica serovar Typhimurium contains three paralogous TacAT systems that block bacterial translation. We determined the crystal structures of the three TacAT complexes to understand the structural basis of specific TA neutralization and the evolution of such specific pairing. In the present study, we show that alteration of a discrete structural add-on element on the toxin drives specific recognition by their cognate antitoxin underpinning insulation of the three pairs. Similar to other TA families, the region supporting TA-specific pairing is key to neutralization. Our work reveals that additional TA interfaces beside the main neutralization interface increase the safe space for evolution of pairing specificity.

Significance of Perfluoroalkyl Substances (PFAS) in Food Packaging.

Food safety authorities and the food industry are focused on uses of perfluoroalkyl substances (PFAS) in various food-contact packaging applications. Not widely known until recently, certain PFAS occur in paper-based packaging materials typically at parts-per-billion to parts-per-million concentrations. These substances are nonintentionally added substances (NIAS) and are attributed to residues from recycled fiber and paperboard used in the manufacture of new food packaging products. Low concentration PFAS detection has generated debate in the food industry and among scientific and governmental organizations about understanding their significance in food-contact products because certain PFAS are intentionally added to some food packaging materials. Distinguishing between both sources of PFAS in food packaging is essential for regulatory compliance purposes. In this paper, we describe ongoing research using contact angle measurement analysis to determine limits of performance (LOP) for perfluorocarboxylic acids (PFCAs) (C4, C6, C8, and C10) on the surface of recycled paper packaging materials. We find that the LOP concentrations for PFCAs ranged from 37 ppm (C10) to higher than 1238 ppm (C4). Because there is no economic justification for the presence of PFAS that do not provide functional performance, these LOP concentrations can reliably be considered as NIAS thresholds. This analytical method and the resulting test data are able to differentiate the source of PFAS in food packaging. Future research will broaden the test method to include measurements of fluorotelomer, sulfonamide, and fluoropolymer substances to develop a more comprehensive understanding of PFAS performance and NIAS concentration thresholds. Integr Environ Assess Manag 2021;17:7-12. © 2020 SETAC.