Psychotherapy Disruption Before and After the Transition to Virtual Mental Health Care Induced by the COVID-19 Pandemic.

OBJECTIVE: This study aimed to examine population-level disruption in psychotherapy before and after the rapid shift to virtual mental health care induced by the onset of the COVID-19 pandemic in the United States. METHODS: This retrospective study used electronic health record and insurance claims data from three U.S. health systems. The sample included 110,089 patients with mental health conditions who were members of the health systems' affiliated health plans and attended at least two psychotherapy visits from June 14, 2019, through December 15, 2020. Data were subdivided into two 9-month periods (before vs. after COVID-19 onset, defined in this study as March 14, 2020). Psychotherapy visits were measured via health records and categorized as in person or virtual. Disruption was defined as a gap of >45 days between visits. RESULTS: Visits in the preonset period were almost exclusively in person (97%), whereas over half of visits in the postonset period were virtual (52%). Approximately 35% of psychotherapy visits were followed by a disruption in the preonset period, compared with 18% in the postonset period. Disruption continued to be less common (adjusted OR=0.45) during the postonset period after adjustment for visit, mental health, and sociodemographic factors. The magnitude of the difference in disruption between periods was homogeneous across sociodemographic characteristics but heterogeneous across psychiatric diagnoses. CONCLUSIONS: This study found fewer population-level disruptions in psychotherapy receipt after rapid transition to virtual mental health care following COVID-19 onset. These data support the continued availability of virtual psychotherapy.

Factors Associated With Interest in Engaging in Psychological Interventions for Pain Management.

OBJECTIVE: Engagement in evidence-based psychological interventions for pain management is low. Identifying characteristics associated with interest in interventions can inform approaches to increase uptake and engagement. The purpose of this study was to examine factors associated with interest in psychological interventions among persons with chronic noncancer pain receiving prescription opioids. METHODS: Participants with chronic noncancer pain and a new 30 to 90 day opioid prescription were recruited from 2 health systems. Participants (N=845) completed measures regarding pain, opioid use, psychiatric symptoms, emotional support, and interest in psychological interventions for pain management. RESULTS: There were 245 (29.0%) participants who reported a high interest in psychological interventions for pain management. In bivariate analyses, variables associated with interest included younger age, female sex, greater pain severity, greater pain interference, greater number of pain sites, lower emotional support, depression, anxiety, and post-traumatic stress disorder ( P <0.05). In a multivariate model, greater pain severity (odds ratio [OR]=1.17; CI: 1.04-1.32), depression (OR=2.10; CI: 1.39-3.16), post-traumatic stress disorder (OR=1.85; CI: 1.19-2.95), and lower emotional support (OR=0.69; CI: 0.5-0.97) remained statistically significant. DISCUSSION: The rate of interest in psychological interventions for pain management was low, which may indicate that patients initiating opioid treatment of chronic noncancer pain have low interest in psychological interventions. Greater pain severity and psychiatric distress were related to interest, and patients with these characteristics may especially benefit from psychological interventions. Providers may want to refer to psychological interventions before or when opioids are initiated. Additional work is needed to determine whether this would reduce long-term opioid use.

Making RNA: Using T7 RNA polymerase to produce high yields of RNA from DNA templates.

RNA is playing an ever-growing role in molecular biology and biomedicine due to the many ways it influences gene expression and its increasing use in modern therapeutics. Hence, production of RNA molecules in large quantity and high purity has become essential for advancing basic scientific research and for developing next-generation therapeutics. T7 RNA polymerase (RNAP) is a DNA-dependent RNA polymerase of bacteriophage origin and it is the most widely-utilized tool enzyme for producing RNA. Here we describe a set of robust methods for in vitro transcribing RNA molecules from DNA templates using T7 RNAP, along with a set of subsequent RNA purification schemes. In the first part of this chapter, we provide the general method for T7 RNAP-based in vitro transcription and technical notes for troubleshooting failed or inefficient transcription. We also provide modified protocols for preparing specialized RNA transcripts. In the second part, we provide two purification methods using either gel-based denaturing purification or size exclusion column-based non-denaturing purification for isolating high-purity RNA products from transcription reaction mixtures and preparing them for downstream applications. This chapter is designed to provide researchers with versatile ways to efficiently generate RNA molecules of interest and a troubleshooting guide should they encounter problems while working with in vitro transcription using T7 RNAP.

Systematic detection of tertiary structural modules in large RNAs and RNP interfaces by Tb-seq.

Compact RNA structural motifs control many aspects of gene expression, but we lack methods for finding these structures in the vast expanse of multi-kilobase RNAs. To adopt specific 3-D shapes, many RNA modules must compress their RNA backbones together, bringing negatively charged phosphates into close proximity. This is often accomplished by recruiting multivalent cations (usually Mg2+), which stabilize these sites and neutralize regions of local negative charge. Coordinated lanthanide ions, such as terbium (III) (Tb3+), can also be recruited to these sites, where they induce efficient RNA cleavage, thereby revealing compact RNA 3-D modules. Until now, Tb3+ cleavage sites were monitored via low-throughput biochemical methods only applicable to small RNAs. Here we present Tb-seq, a high-throughput sequencing method for detecting compact tertiary structures in large RNAs. Tb-seq detects sharp backbone turns found in RNA tertiary structures and RNP interfaces, providing a way to scan transcriptomes for stable structural modules and potential riboregulatory motifs.

Sarecycline inhibits protein translation in Cutibacterium acnes 70S ribosome using a two-site mechanism.

Acne vulgaris is a chronic disfiguring skin disease affecting ∼1 billion people worldwide, often having persistent negative effects on physical and mental health. The Gram-positive anaerobe, Cutibacterium acnes is implicated in acne pathogenesis and is, therefore, a main target for antibiotic-based acne therapy. We determined a 2.8-Šresolution structure of the 70S ribosome of Cutibacterium acnes by cryogenic electron microscopy and discovered that sarecycline, a narrow-spectrum antibiotic against Cutibacterium acnes, may inhibit two active sites of this bacterium's ribosome in contrast to the one site detected previously on the model ribosome of Thermus thermophilus. Apart from the canonical binding site at the mRNA decoding center, the second binding site for sarecycline exists at the nascent peptide exit tunnel, reminiscent of the macrolides class of antibiotics. The structure also revealed Cutibacterium acnes-specific features of the ribosomal RNA and proteins. Unlike the ribosome of the Gram-negative bacterium Escherichia coli, Cutibacterium acnes ribosome has two additional proteins, bS22 and bL37, which are also present in the ribosomes of Mycobacterium smegmatis and Mycobacterium tuberculosis. We show that bS22 and bL37 have antimicrobial properties and may be involved in maintaining the healthy homeostasis of the human skin microbiome.

Direct tracking of reverse-transcriptase speed and template sensitivity: implications for sequencing and analysis of long RNA molecules.

Although reverse-transcriptase (RT) enzymes are critical reagents for research and biotechnology, their mechanical properties are not well understood. In particular, we know little about their relative speed and response to structural obstacles in the template. Commercial retroviral RTs stop at many positions along mixed sequence templates, resulting in truncated cDNA products that complicate downstream analysis. By contrast, group II intron-encoded RTs appear to copy long RNAs with high processivity and minimal stops. However, their speed, consistency and pausing behavior have not been explored. Here, we analyze RT velocity as the enzyme moves through heterogeneous sequences and structures that are embedded within a long noncoding RNA transcript. We observe that heterogeneities in the template are highly disruptive to primer extension by retroviral RTs. However, sequence composition and template structure have negligible effects on behavior of group II intron RTs, such as MarathonRT (MRT). Indeed, MRT copies long RNAs in a single pass, and displays synchronized primer extension at a constant speed of 25 nt/sec. In addition, it passes through stable RNA structural motifs without perturbation of velocity. Taken together, the results demonstrate that consistent, robust translocative behavior is a hallmark of group II intron-encoded RTs, some of which operate at high velocity.

Exploring gender, psychiatric symptoms, and eating behaviors as predictors of attrition to bariatric surgery.

BACKGROUND: Only a small proportion of eligible individuals undergo bariatric surgery. The purpose was to examine attrition to surgery and whether psychiatric symptoms and eating behaviors differentially predicted attrition among men and women. METHOD: Data was collected from a retrospective chart review of 313 patients who underwent a pre-surgical psychosocial evaluation. RESULTS: The overall attrition rate was 33.5%; 42.6% of men and 31.7% of women experienced attrition. In the multivariate analysis of the entire sample, White patients (OR = 2.33, CI: 1.33, 4.08) and those without a history of binge eating (OR = 2.71, CI: 1.23, 5.97) were more likely to undergo surgery. In a multivariate analysis of women only, race and binge eating independently predicted attrition; however, no factors significantly predicted attrition among men. CONCLUSIONS: Factors identified at the pre-surgical psychosocial evaluation can identify patients at risk for attrition, and these factors may differ for men and women.

Practice patterns of bupropion co-prescription with antipsychotic medications.

Objective: Bupropion is one of the few medications with an FDA indication for smoking cessation. This is of particular significance due to the high co-morbidity of tobacco use disorder in patients with schizophrenia spectrum and other psychotic disorders. We sought to determine whether historical suggestions of bupropion's pro-dopaminergic activity lead prescribers to withhold bupropion in populations receiving antipsychotic medications. Methods: The prevalence in clinical practice of the combination of bupropion and 10 antipsychotic formulations was determined by a computer review of the Genoa Healthcare database for all prescribers at 10 participating community mental health centers. Actual prevalence was compared with expected prevalence using the test of proportions. A Bonferroni correction for multiple comparisons was included. Results: Clozapine, p = 0.0004, and the microsphere formulation of risperidone, p = 0.0045, were prescribed with bupropion significantly less often that chance. None of the other eight antipsychotic formulations were prescribed significantly differently than chance. Conclusions: The co-prescription of bupropion and antipsychotic medication may be affected by historical misconceptions regarding bupropion's purportedly pro-dopamine properties. Viable options for the treatment of tobacco use disorder should not be discounted prematurely in patients with schizophrenia spectrum and other psychotic disorders. We suggest further study on the safety and efficacy of the combination of bupropion and antipsychotic medication is needed.

Disordered eating and eating disorders among women seeking fertility treatment: A systematic review.

The purpose of this systematic review is to evaluate the prevalence of disordered eating and eating disorders among women seeking fertility treatment.Observational studies were searched in Ovid MEDLINE, Web of Science, Embase, and PsycInfo. Studies published prior to September 2020 when the search was conducted were considered. Inclusion criteria included (1) original and empirical research, (2) published in a peer-reviewed journal, and (3) reported on disordered eating among women seeking fertility treatment in the sample or reported on prevalence of eating disorders among women seeking fertility treatment in the sample. Independent screening of abstracts was conducted by two authors (LH and AH). Ten studies met the inclusion criteria. Sample size, study location, measures, and results for each study in this review were reported.Among women pursuing fertility treatment, rates of current eating disorders ranged from 0.5 to 16.7%, while past eating disorder prevalence rates ranged from 1.4 to 27.5%. Current anorexia nervosa or bulimia nervosa was reported by up to 2% and 10.3% of women, respectively, while history of anorexia nervosa or bulimia nervosa was reported by up to 8.5% and 3.3% of women, respectively. Binge eating disorder or other eating disorders were reported by up to 18.5% and 9.1% of women, respectively. Disordered eating pathology was endorsed by 1.6 to 48% of women seeking fertility treatment. Endorsement of pathological eating attitudes was generally higher among women seeking fertility treatment with current or past eating disorders as compared to community samples, with the exception of dietary restraint. Rates of current and past eating disorders are higher among women seeking fertility treatment than in the general population. Providers treating women with infertility should be cognizant of these prevalence rates and consider screening for eating pathology in their patients as this may contribute to their likelihood of successful conception and/or subsequent pregnancy outcomes.

The Mucosally-Adherent Rectal Microbiota Contains Features Unique to Alcohol-Related Cirrhosis.

Most studies examining correlations between the gut microbiota and disease states focus on fecal samples due to ease of collection, yet there are distinct differences when compared to samples collected from the colonic mucosa. Although fecal microbiota has been reported to be altered in cirrhosis, correlation with mucosal microbiota characterized via rectal swab has not been previously described in this patient population. We conducted a cross-sectional analysis using 39 stool and 39 rectal swabs from adult patients with cirrhosis of different etiologies and performed shotgun metagenomic sequencing. Bacterial growth studies were performed with Escherichia coli. Two asaccharolytic bacterial taxa, Finegoldia magna and Porphyromonas asaccharolytica, were increased in rectal swabs relative to stool (FDR < 0.01). Genomic analysis of the microbiome revealed 58 genes and 16 pathways that differed between stool and rectal swabs (FDR < 0.05), where rectal swabs were enriched for pathways associated with protein synthesis and cellular proliferation but decreased in carbohydrate metabolism. Although no features in the fecal microbiome differentiated cirrhosis etiologies, the mucosal microbiome revealed decreased abundances of E. coli and Enterobacteriaceae in alcohol-related cirrhosis relative to non-alcohol related cirrhosis (FDR < 0.05). In vitro bacterial culture studies showed that physiological concentrations of ethanol and its oxidative metabolites inhibited E. coli growth in a pH- and concentration-dependent manner. Characterization of the mucosally associated gut microbiome via rectal swab revealed findings consistent with amino acid/nitrogen abundance versus carbohydrate limitation in the mucosal microenvironment as well as unique features of alcohol-related cirrhosis possibly consistent with the influence of host-derived metabolites on the composition of mucosally adherent microbiota.

Management of Laryngotracheal Stenosis in Obesity. Is This Another Co-morbidity that Can Be Improved with Weight Loss Following Bariatric Surgery?

PURPOSE: Bariatric surgery improves several obesity-related comorbidities. Laryngotracheal stenosis is a rare condition that is usually managed with repeated endoscopic airway interventions and reconstructive airway surgery. The outcome of these definitive operations is worse in individuals with obesity. There are no studies investigating the effect of weight loss following bariatric surgery in the management of laryngotracheal stenosis. MATERIALS AND METHODS: In an observational study, consecutive patients with a BMI over 35 kg/m2 and laryngotracheal stenosis were prospectively recruited to a bariatric and airway stenosis database in two tertiary care centres. Patients were treated with laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy and control subjects were managed conservatively. RESULTS: A total of eleven patients with an initial body mass index of 43 kg/m2 (37-45) were enrolled to this study. Six patients underwent bariatric surgery and five subjects were treated conservatively. After 12 months, the total weight loss of patients undergoing bariatric surgery was 19.4% (14-24%) whilst 2.3% (1-3%) in the control group. The annual number of endoscopic airway interventions following bariatric surgery reduced (p = 0.002). Higher weight loss in patients led to less frequent interventions compared to control subjects (p = 0.004). Patients undergoing laryngotracheal reconstruction following bariatric surgery needed less endoscopic intervention, an annual average of 1.9 interventions before vs 0.5 intervention after. Conservatively managed control subjects required more frequent endoscopic intervention, 1.8 before vs 3.4 after airway reconstruction. CONCLUSION: Bariatric surgery reduced the number of endoscopic airway interventions and enabled patients to undergo successful definitive airway reconstructive surgery.

Global Microbiota-Dependent Histone Acetylation Patterns Are Irreversible and Independent of Short Chain Fatty Acids.

BACKGROUND AND AIMS: Although germ-free mice are an indispensable tool in studying the gut microbiome and its effects on host physiology, they are phenotypically different than their conventional counterparts. While antibiotic-mediated microbiota depletion in conventional mice leads to physiologic alterations that often mimic the germ-free state, the degree to which the effects of microbial colonization on the host are reversible is unclear. The gut microbiota produce abundant short chain fatty acids (SCFAs), and previous studies have demonstrated a link between microbial-derived SCFAs and global hepatic histone acetylation in germ-free mice. APPROACH AND RESULTS: We demonstrate that global hepatic histone acetylation states measured by mass spectrometry remained largely unchanged despite loss of luminal and portal vein SCFAs after antibiotic-mediated microbiota depletion. In contrast to stable hepatic histone acetylation states, we see robust hepatic transcriptomic alterations after microbiota depletion. Additionally, neither dietary supplementation with supraphysiologic levels of SCFA nor the induction of hepatocyte proliferation in the absence of microbiota-derived SCFAs led to alterations in global hepatic histone acetylation. CONCLUSIONS: These results suggest that microbiota-dependent landscaping of the hepatic epigenome through global histone acetylation is static in nature, while the hepatic transcriptome is responsive to alterations in the gut microbiota.