Functional resilience and overall survival in adults treated for advanced non-small-cell lung cancer.

PURPOSE: As more treatments emerge for advanced, stage IV non-small-cell lung cancer (NSCLC), oncologists have difficulty predicting functional resiliency versus functional decline throughout cancer treatment. Our study evaluates functional resilience among patients with advanced NSCLC. METHODS: Functional status was evaluated through 12 months of follow-up based on disability score using the modified EQ-5D-5L (mEQ-5D-5L) survey. Participants were classified into 4 groups: functional maintenance, decline, resilient, or variable. Characteristics of 207 participants with newly diagnosed NSCLC included demographics, comorbidities, baseline Eastern Cooperative Oncology Group (ECOG) performance status (PS), mEQ-5D-5L scores, psychological symptoms, and lung cancer-specific symptoms. Treatment toxicity and grade were recorded. Resilience was defined as improvement from baseline disability scores. A 1-point increase in functional status score represents a 0.5 standard deviation change on the mEQ-5D-5L. Differences between the 4 groups were determined through Fisher's exact test or ANOVA. Kaplan-Meier curves describe overall survival (baseline through 18 months) stratified by baseline mEQ-5D-5L scores. RESULTS: Among participants, 42.0 % maintained functional status, 37.7 % experienced functional decline, 10.6 % were resilient, and 9.7 % had variable functional status. Participants with the best baseline function (score of 0) had the longest overall survival and participants with the worst baseline function (score of 5 + ) had the shortest overall survival. Among the healthiest patients, early score increases indicated shorter overall survival. Baseline ECOG PS was not associated with overall survival (p = 0.47). CONCLUSION: Baseline functional status may help better predict functional resiliency and overall survival than ECOG PS among patients receiving treatment for advanced NSCLC.

Resiliency among older adults receiving lung cancer treatment (ROAR-LCT): A novel supportive care intervention for older adults with advanced lung cancer.

INTRODUCTION: Novel supportive care interventions designed for an aging population with lung cancer are urgently needed. We aimed to determine the feasibility of a novel supportive care physical therapy (PT) plus progressive muscle relaxation (PMR) intervention delivered to older adults with advanced lung cancer in the United States (US). MATERIALS AND METHODS: This clinical trial, Resiliency Among Older Adults Receiving Lung Cancer Treatment (ROAR-LCT: NCT04229381), recruited adults aged ≥60 years with unresectable stage III/IV non-small cell (NSCLC) or small cell lung cancer (SCLC) receiving cancer treatment at The James Thoracic Oncology Center (planned enrollment, N = 20). There were no exclusion criteria pertaining to performance status, laboratory values, prior cancer diagnoses, comorbidities, or brain metastases. Participants were evaluated by PT and psychology and given an exercise pedaler, resistance bands, a relaxation voice recording, and instructions at study initiation. Participants were evaluated in-person by PTs and psychologists at the start and end of the 12-session intervention, with the intervening sessions conducted via virtual health. Participants completed self-reported measures of functional status, symptoms, and mood longitudinally with the following instruments: EQ-5D-5L, Patient Health Questionnaire-9, and General Anxiety Disorder-7. PT assessments included the Short Physical Performance Battery (SPPB) and the two-minute walk test. Feasibility was defined as at least 60% of participants completing at least 70% of all intervention sessions. Optional gut microbiome samples and activity monitoring data (ActiGraph®) were also collected. RESULTS: The ROAR-LCT study concluded after consenting 22 patients. Among the 22 consented, 18 (81.8%) started the intervention; 11 participants (61.1%) completed at least 70% of all study sessions. All participants with SCLC completed the intervention. Reasons for withdrawal included progression of disease or hospitalization. The majority (88.9%) of patients who started were able to complete at least one virtual health session. Participants' functional status, SPPB, depression, and anxiety scores were stable from pre- to post-intervention. Participants who withdrew had worse baseline scores across domains. Seven microbiome and six ActiGraph® samples were collected. DISCUSSION: This is one of the first PT + PMR supportive care interventions using virtual health among older adults with advanced lung cancer to achieve feasibility in the US.

Crystal Structure Landscape of Diarylethene-Based Crystalline Solids: A Comprehensive CSD Analysis.

Diarylethenes (DAEs) are an exciting class of stimulus-responsive organic molecules that exhibit electrocyclization reactions upon exposure to light, heat, or other stimuli. The rational design of DAE-based crystalline materials is, however, complicated by the presence of DAE atropisomers, only one of which is photoactive. Data mining of the CSD produced 1349 unique molecular DAE structures that were subsequently analyzed according to selected chemical and geometric attributes. Additional analyses were performed on 1078 dithienylethene (DTE) structures-the largest subgroup within the ensemble. The crystal structure landscape, based upon D-D parameterization and analysis, revealed a vast array of molecular geometries, many of which may not correspond to energetic minima. The analyses link various chemical and geometric parameters to isomers observed in the lattice and their reactivity; however, potential biases intrinsic to this ensemble of structures complicate the determination of causal relationships. We believe that this retrospective comprehensive analysis of DAE structures represents an important step for understanding more broadly the crystal landscape of this class of materials.

Fertility Perspectives and Concerns in Adolescents With PCOS Compared to Controls.

PURPOSE: Polycystic ovary syndrome (PCOS) is prevalent in young females and is known to affect fertility. Minimal research has examined fertility perspectives in adolescents with PCOS, despite adult research revealing relationships between infertility and psychosocial well-being and quality of life. We examined fertility perspectives/concerns in adolescents with PCOS and an age- and body mass index (BMI)-matched control group and explored associations with quality of life. METHODS: This was a cross-sectional study of female adolescents (13-21 years of age) with PCOS (n = 50) and age- and BMI-matched controls (n = 50), recruited at a large Midwestern pediatric center. Surveys assessed sociodemographics, hirsutism, fertility perspectives and quality of life. Descriptive statistics and Welch's 2-sample t-tests were used to examine fertility perspectives and quality of life. RESULTS: Of the 103 approached, 100 participants were enrolled (97% recruitment rate), with 50 participants in each group. Parenthood goals did not significantly differ between groups; >70% expressed desire to have biological children. However, PCOS participants reported significantly higher concerns about future fertility (p < .01) without differences in fertility knowledge or support (p = .53). Most PCOS participants stated they would feel angry if their provider withheld this information and reported wanting more information. Quality of life did not differ between groups. DISCUSSION: Our study suggests that irrespective of PCOS status, most adolescents aspire to parenthood. Notably, many with PCOS lack awareness of infertility risks but express heightened concerns. In contrast to adult studies, fertility concerns among adolescents with PCOS were not associated with decreased quality of life, suggesting that earlier fertility counseling may improve outcomes.

The FITNESS study: longitudinal geriatric assessment, treatment toxicity, and biospecimen collection to assess functional disability among older adults with lung cancer.

Introduction: Older adults with chronic disease prioritize functional independence. We aimed to describe the feasibility of capturing functional disability and treatment toxicity among older adults with lung cancer using a longitudinal comprehensive geriatric assessment (CGA) and molecular biomarkers of aging. Methods: This prospective study included adults ≥60 years with any newly diagnosed non-small-cell lung cancer. Participants were recruited from central Ohio (2018-2020). Study assessments included the Cancer and Aging Research Group CGA (CARG-CGA), short physical performance battery (SPPB), and the blessed orientation-memory concentration (BOMC) test at baseline, 3, 6, and 12 months. Activities of daily living (ADLs) and instrumental ADLs (IADLs), quality of life (QoL, PROMIS 10), and treatment toxicity were captured monthly. Stool and blood were collected to characterize the gut microbiome and age-related blood biomarkers. Results: This study enrolled 50 participants with an average age of 71.7 years. Ninety-two percent of participants were Caucasian, 58% were male, and all were non-Hispanic. Most had advanced stage (stage III/IV: 90%; stage I/II: 10%), with adenocarcinoma the predominant histologic subtype (68% vs. 24% squamous). First-line treatments included chemotherapy (44%), immune checkpoint inhibitors (ICIs, 22%), chemotherapy and ICIs (30%), or tyrosine kinase inhibitors (4%). The median baseline CARG toxicity score was 8 (range 2-12). Among patients with treatment-related toxicity (n = 49), 39 (79.6%) cases were mild (grade 1-2), and 10 (20.4%) were moderate to severe (≥ grade 3). Treatment toxicity was greater among those with a CARG score ≥8 (28.0% vs. 13.6%). Higher IADL independence, QoL, and SPPB scores at baseline were positively associated with Candidatus Gastranaerophilales bacterium, Lactobacillus rogosae, and Enterobacteria phage P4. Romboutsia ilealis, Streptococcus, and Lachnoclostridium sp An138 and T cell lag3 and cd8a were associated with worse IADLs, QoL, and SPPB scores at baseline. Discussion: A longitudinal CGA and biomarker collection is feasible among older adults undergoing lung cancer treatment. Gut microbe and T cell gene expression changes correlated with subjective and objective functional status assessments. Future research will test causality in these associations to improve outcomes through novel supportive care interventions to prevent functional disability.

Methyl 2-hy-droxy-4-iodo-benzoate.

The structure of the title compound, C8H7IO3, at 90 K has monoclinic (P21/c) symmetry. The extended structure is layered and displays inter-molecular and intra-molecular hydrogen bonding arising from the same OH group.

Implementation and Outcomes of an Academic Peer Coaching Program for Pediatric Residents.

Introduction Academic coaching fosters self-directed learning and is growing in popularity within residency programs. Implementation is often limited by available faculty time and funding. Peer coaching is an emerging alternative but is not well studied. This study aims to demonstrate the acceptability, feasibility, and efficacy of a resident peer coaching program. Methodology In the 2021-2022 academic year, within a large pediatric residency program, we selected and trained senior residents as coaches and interns who opted in as coachees. Coaching dyads began meeting in the fall and worked toward individualized goals throughout the year; control interns participated in routine didactics. Outcomes included Accreditation Council for Graduate Medical Education (ACGME) milestone scores and a self-assessment survey (SAS). Results We enrolled 15/42 (36%) interns as coachees, with the remaining 27 (64%) as controls. Narrative feedback from coaches and coachees was overall positive, and time commitment was feasible for program staff (10-12 hours/month), coaches (three to four hours/month), and coachees (one to two hours/month) with minimal financial needs. Post-intervention, more coachees than controls scored ≥4.0 on ACGME milestones systems-based practice 3 (SBP3; 3/15, 20%, vs. 2/27, 7%), SBP4 (4/15, 27%, vs. 5/27, 19%), and practice-based learning and improvement 1 (4/15, 27%, vs. 3/27, 11%). SAS response rate was 8/15 (53%) for coachees and 5/27 (19%) for controls. More coachees than controls reported baseline difficulty with time management often (3/8, 38%, vs. 1/5, 20%); only coachees improved post-intervention, with 0/8 (0%) having difficulty often versus 2/5 (40%) of controls. Conclusions Resident peer coaching is acceptable and feasible to implement. Coachees reported more improvement in time management than controls, and ACGME milestone scores suggest improved use of evidence-based medicine and interprofessional care coordination among coachees.

Examining Barriers to Early Hearing Diagnosis.

PURPOSE: Many factors create barriers for early hearing detection and intervention (EHDI), especially those related to unfavorable social determinants of health (SDOH). The primary aim of this study was to evaluate diagnostic timing of infants at risk for congenital hearing loss in consideration of known barriers. Understanding the specific barriers to early diagnosis can inform interventions to improve timeliness of diagnosis and subsequent habilitation. METHOD: A retrospective chart review was completed for infants referred for diagnostic audiologic testing at a tertiary urban-setting Children's Hospital from 2018 to 2021. After exclusion criteria were applied, 1,488 infants were included in the analysis. Various factors were recorded from electronic medical records including those specific to SDOH. Time to diagnosis was derived and compared across five factors of interest that have previously been shown to impact diagnostic timeline, including (a) insurance type, (b) race/ethnicity, (c) presence of middle ear dysfunction at first auditory brainstem response (ABR), (d) proximity to diagnostic center, and (e) diagnostic timing before and during/after the COVID-19 pandemic. RESULTS: Across the study time period, 77% of infants referred for diagnostic testing had confirmed diagnosis by the EHDI benchmark of 3 months. Analysis of time to diagnosis across factors of interest revealed no clinically significant differences for insurance type, race/ethnicity, proximity to diagnostic center, or timing in reference to the COVID-19 pandemic. Presence of middle ear dysfunction on first ABR was found to significantly protract final diagnostic timing. CONCLUSIONS: Although some known barriers for EHDI can be universal, other factors may have a differential impact on an infant's timeline to diagnosis based on their specific location, which can interact differently with additional known barriers. Understanding local challenges will serve to better guide programs in implementing facilitators that will address their specific needs for improved outcomes.

Evaluation of the Diversity, Equity, and Inclusion Curriculum of a Pediatrics Residency Program.

OBJECTIVES: Diversity, equity, and inclusion (DEI) training is essential to graduate medical education, but it lacks standardization. Although the impact of providers' biases and cultural competency on patient outcomes is well documented, the value of and satisfaction with DEI curricula in Pediatrics residency training programs is not well studied. This study aimed to complete a cross-sectional evaluation of the current DEI curriculum at a large Pediatrics-focused academic institution and identify areas of perceived deficiency among Pediatrics trainees. METHODS: Residents and residency program directors completed surveys in 2020. Respondents evaluated the DEI curriculum of the program and the competency of residents to complete patient care related to specific DEI-oriented actions. Our analysis used descriptive statistics. RESULTS: In total, 48 of 137 resident trainees (35%) and 7 of 9 program leaders (78%) completed the survey. Respondents were most dissatisfied with current education related to implicit bias, refugee/immigrant health, and lesbian, gay, bisexual, transgender, queer, intersex, asexual, and other health topics. Respondents reported low resident competency in DEI-focused patient care tasks and did not view residents as competent to address the healthcare needs of patients and families experiencing racism. CONCLUSIONS: Pediatrics residents and program directors consider DEI topics important and express a need for more robust DEI curricula.

Chlorfenapyr Crystal Polymorphism and Insecticidal Activity.

Four crystalline polymorphs of the proinsecticide chlorfenapyr [4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-trifluoromethyl-1H-pyrrole-3-carbonitrile] have been identified and characterized by polarized light optical microscopy, differential scanning calorimetry, Raman spectroscopy, X-ray diffraction, and electron diffraction. Three of the four structures were considered polytypic. Chlorfenapyr polymorphs show similar lethality against fruit flies (Drosophila melanogaster) and mosquitoes (Anopheles quadrimaculatus) with the least stable polymorph showing slightly higher lethality. Similar activities may be expected to be consistent with structural similarities. Knockdown kinetics, however, depend on an internal metabolic activating step, which further complicates polymorph-dependent bioavailability.

Incidence of postpartum depression in low-income cannabis users with and without a history of depression.

While past research has linked cannabis use in pregnancy with a history of depression, sparse literature exists on cannabis use during pregnancy and postpartum depression (PPD). In this study, we aimed to better understand the association between PPD and cannabis use during pregnancy in those with and without a history of depression. This was a retrospective cohort study of patients who received prenatal care at a single institution between January 2017 and December 2019. Patient demographics, obstetric history, depression history, substance use history, and Edinburgh Postnatal Depression Scale (EPDS) scores were extracted from patients' medical records. Modified Poisson Regression with robust standard errors was used to estimate the relative risk (RR) of screening positive for PPD, adjusting for age at delivery, race/ethnicity, insurance type, marital status, and smoking history. Among the 799 subjects meeting inclusion criteria, 15.9% used cannabis during pregnancy. There was an increased risk of screening positive for PPD among prenatal cannabis users compared to non-users (aRR = 1.60, 95% CI: (1.05, 2.45)). Among individuals with a history of depression, the adjusted relative risk of screening positive for symptoms of PPD at the postpartum visit was 1.62 times greater in cannabis users compared to non-users (95% CI: (1.02, 2.58)). Prenatal cannabis use is associated with screening positive for PPD, particularly in those individuals with a history of depression. These results should discourage women with depression from self-medicating with cannabis in pregnancy and provide additional support to the existing recommendations to abstain from prenatal cannabis use.

Fluid-attenuated inversion-recovery sequence with fat suppression as an alternative to contrast-enhanced MRI in pediatric synovitis.

BACKGROUND: Non-contrast magnetic resonance imaging (MRI) fluid-attenuated inversion-recovery sequence (FLAIR) with fat suppression (FS) has not been validated in children. OBJECTIVE: Compare FLAIR to T1-weighted post contrast (T1CE) in the detection of knee synovitis. METHODS AND MATERIALS: Institutional review board (IRB) waived consent. Children who underwent T1CE and FLAIR sequences of the knee on a 3-T magnet from April 2021 to December 2021 were included. Two pediatric radiologists assessed axial FLAIR and T1CE images for synovitis and synovial thickness. Reliability and agreement were assessed. Sensitivities, specificities, and accuracy were calculated for FLAIR using T1CE as reference standard. RESULTS: In total, 42 knees (39 patients) were assessed (median age 12.9 years (2.3-17.8 years); 62% male, 38% female). Readers judged 20/42 (48%) knees to have synovitis. Sensitivity of FLAIR for reader 1 was 79% (19/24; 95% CI 0.58, 0.93) and 84% (16/19; 95% CI 0.60, 0.97) for reader 2. Specificity of FLAIR for reader 1 was 94% (17/18; 95% CI 0.73, 1) and 83% (19/23; 95% CI 0.61, 0.95) for reader 2. Accuracy for readers 1 and 2 was 86% (36/42; 95% CI 0.71, 0.95) and 83% (35/42; 95% CI 0.69, 0.93), respectively. Inter-reader reliability was good (0.75-0.90) for synovial measurements for FLAIR (ICC = 0.80; 95% CI 0.71, 0.86) and moderate for T1 CE (ICC = 0.62 (95% CI 0.48, 0.73)). CONCLUSION: FLAIR FS depicts synovium in the pediatric knee with similar reliability to T1 CE and may be an acceptable alternative to contrast in the initial diagnosis of synovitis.

The Effect of a Psychologically Informed Video Series to Treat Adolescents With Patellofemoral Pain: A Randomized Controlled Trial.

OBJECTIVE: To test whether a series of brief, psychologically informed educational videos added to physical therapy improved function among adolescents with patellofemoral pain. The secondary aims were to assess pain and psychological beliefs. DESIGN: A double-blinded randomized controlled trial. METHODS: Sixty-eight adolescents with patellofemoral pain were randomly assigned to view brief, psychologically informed videos (n = 34) or control videos (n = 34) in addition to usual care physical therapy. The psychologically informed videos targeted fear-avoidance beliefs, kinesiophobia, and pain catastrophizing. The control videos conveyed basic anatomy, biomedical factors, and lower extremity mechanics. Outcomes were assessed at baseline, 3 weeks, 6 weeks (primary end point), and 3 months. The primary outcome was change in the Anterior Knee Pain Scale. Secondary outcomes were changes in Numeric Pain-Rating Scale and psychological beliefs (Modified Fear-Avoidance Beliefs Questionnaire-Physical Activity, Tampa Kinesiophobia Scale-11, and Pain Catastrophizing Scale-Child). RESULTS: Adolescents in the psychologically informed group experienced significantly greater improvements in function (Anterior Knee Pain Scale mean difference = 8 points; 95% CI: 2.2, 13.2; P = .01) and pain (Numeric Pain-Rating Scale mean difference = 1.2 points; 95% CI: 0.1, 2.4; P = .04) at 6 weeks compared to the control group. The psychologically informed group had significantly greater reductions in psychological beliefs over time than the control group (P≤.001; partial η2 = 0.32). CONCLUSION: Incorporating psychologically informed education into physical therapy care improved function, pain, and psychological beliefs to a greater extent than the control group. J Orthop Sports Phys Ther 2023;53(10):1-9. Epub: 14 September 2023. doi:10.2519/jospt.2023.12041.

Development of a scalar-based geometric parameterization approach for the crystal structure landscape of dithienylethene-based crystalline solids.

Dithienylethenes (DTEs) are a promising class of organic photoswitches that can be used to create crystalline solids with properties controlled by light. However, the ability of DTEs to adopt multiple conformations, only one of which is photoactive, complicates the rational design of these materials. Herein, the synthesis and structural characterization of 19 crystalline solids containing a single DTE molecule are described. A novel D-D analysis of the molecular geometries obtained from rotational potential energy surface calculations and the ensemble of experimental structures were used to construct a crystal landscape for DTE. Of the 19 crystal structures, 17 contained photoinactive DTE rotamers and only 2 were photoactive. These results highlight the challenges associated with the design of these materials. Overall, the D-D analysis described herein provides rapid, effective and intuitive means of linking the molecular structure to photoactivity that could be applied more broadly to afford a general strategy for producing photoactive diarylethene-based crystalline solids.

Photocrystallography of [Ru(bpy)2(dmso)2]2+ reveals an O-bonded metastable state.

We report the first instance of observing the phototriggered isomerization of dmso ligands on a bis sulfoxide complex, [Ru(bpy)2(dmso)2], in the crystalline solid state. The solid-state UV-vis spectrum of the crystal demonstrates an increase in optical density around 550 nm after irradiation, which is consistent with the solution isomerization results. Digital images of the crystal before and after irradiation display a notable color change (pale orange to red) and cleavage occurs along planes, (1̄01) and (100), during irradiation. Single crystal X-ray diffraction data also confirms that isomerization is occurring throughout the lattice and a structure that contains a mix of the S,S and O,O/S,O isomer was attained from a crystal irradiated ex situ. In situ irradiation XRD studies reveal that the percentage of the O-bonded isomer increases as a function of 405 nm exposure time.

Improving Access to Early Palliative Care Delivery for Patients With an Advanced Thoracic Malignancy Through an Embedded Oncopalliative Clinic Model.

PURPOSE: Early integration of palliative care (PC) with standard oncology care is driving the development of innovative PC delivery models. METHODS: This was a single-institution retrospective study of outpatient PC before and after the opening of an embedded thoracic oncology-palliative clinic at The Ohio State University. Patients included in the preintervention (October 2017-July 2018) and postintervention (October 2018-July 2019) cohorts had a diagnosis of any non-small-cell lung cancer (stages I-IV) or small-cell lung cancer (limited or extensive stage) and were newly established in the thoracic medical oncology clinic during the study time periods. All patients in the preintervention cohort had access to outpatient PC through a freestanding clinic, while the postintervention cohort had access to both freestanding and embedded clinics. Using time-to-event analyses, we evaluated differences in time intervals from first medical oncology visit to PC referral and first PC visit between cohorts. RESULTS: The majority of patients in both cohorts had metastatic disease at diagnosis. In the postintervention cohort, 20.9% of patients were referred to outpatient PC compared with 9.2% in the preintervention cohort (P < .01). PC referrals for patients outside of Franklin and adjacent counties increased from 4.0% to 14.2% after opening the embedded clinic (P < .01). Completion percentages of PC referrals increased from 57.6% to 76.0% in the preintervention versus postintervention cohorts (P = .048). Median time from palliative referral order to first PC visit decreased from 29 to 20 days (P = .047). Similarly, median time from the first oncology visit to PC referral completion decreased from 103 to 41 days (P = .08). CONCLUSION: Implementation of an embedded PC model was associated with increased access to early PC among patients with thoracic malignancies.

Maternal mood and anxiety effects on the fetal nonstress test.

BACKGROUND: Previous studies have suggested that acute mood states may influence levels of fetal activity. Because the fetal nonstress test relies on markers of fetal activity to suggest fetal wellbeing, its interpretation may be affected by maternal mood. OBJECTIVE: This study sought to determine if there are differences in nonstress test characteristics between pregnant individuals with and without symptoms of mood disorder. STUDY DESIGN: In this prospective cohort study, we recruited pregnant individuals undergoing nonstress test in the third trimester and compared the results of the nonstress test between pregnant individuals with scores above and below the cutoff values on validated screening questionnaires for depression and anxiety symptoms, the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder 7-item scale (GAD-7). Demographic information was collected from each participant at the time of recruitment, and medical information was extracted from the electronic medical record. RESULTS: A total of 68 pregnant individuals were enrolled, 10 (15%) of which screened positive for perinatal mood disorders. There was no significant difference in means of time to reactivity (15.6 [4.8] minutes vs 15.0 [8.0] minutes, P=.77), number of accelerations (0.16/min [0.08] vs 0.16/min [0.10], P>.95), number of fetal movements (17.0 [14.7] vs 19.7 [20.4], P=.62), heart rate baseline (138.0 [7.5] bpm vs 139.2 [9.0] bpm, P=.67) or variability (8.5 [2.5] bpm vs 9.1 (4.3) bpm, P=.51) between pregnant individuals who screen positive for mood disorders and those who did not. CONCLUSION: Fetal heart rate patterns are similar in pregnant individuals with and without symptoms of mood disorder. The results provide reassurance that acute symptoms of anxiety and depression do not have significant effects on the fetal nonstress test.

Enhancing the Stability of Nicotine via Crystallization Using Enantiopure Tartaric Acid Salt Formers.

Crystallization of nicotine, an oil prone to degradation at room temperature, has been demonstrated to be an effective means of creating nicotine-based materials with tunable thermal properties and improved resistance to photo-induced degradation. Herein, we show that both isomers of enantiomerically pure tartaric acid are highly effective salt formers when combined with nicotine. Both salts exhibit enhanced photostability, and with a melting point of 143.1 °C, the salt prepared using d-(-)-tartaric acid possesses one of the highest melting points for a crystalline nicotine solid reported to date.

Association between skeletal muscle mitochondrial dysfunction and insulin resistance in patients with rheumatoid arthritis: a case-control study.

BACKGROUND: Insulin resistance affects a substantial proportion of patients with rheumatoid arthritis (RA). Skeletal muscle mitochondrial dysfunction results in the accumulation of lipid intermediates that interfere with insulin signaling. We therefore sought to determine if lower oxidative phosphorylation and muscle mitochondrial content are associated with insulin resistance in patients with RA. METHODS: This was a cross-sectional prospective study of RA patients. Matsuda index from the glucose tolerance test was used to estimate insulin sensitivity. Mitochondrial content was measured by citrate synthase (CS) activity in snap-frozen muscle samples. Mitochondrial function was measured by using high-resolution respirometry of permeabilized muscle fibers and electron transport chain complex IV enzyme kinetics in isolated mitochondrial subpopulations. RESULTS: RA participants demonstrated lower insulin sensitivity as measured by the Matsuda index compared to controls [median 3.95 IQR (2.33, 5.64) vs. 7.17 (5.83, 7.75), p = 0.02]. There was lower muscle mitochondrial content among RA vs. controls [median 60 mU/mg IQR (45, 80) vs. 79 mU/mg (65, 97), p = 0.03]. Notably, OxPhos normalized to mitochondrial content was higher among RA vs. controls [mean difference (95% CI) = 0.14 (0.02, 0.26), p = 0.03], indicating a possible compensatory mechanism for lower mitochondrial content or lipid overload. Among RA participants, the activity of muscle CS activity was not correlated with the Matsuda index (ρ = - 0.05, p = 0.84), but it was positively correlated with self-reported (IPAQ) total MET-minutes/week (ρ = 0.44, p = 0.03) and Actigraph-measured time on physical activity (MET rate) (ρ = 0.47, p = 0.03). CONCLUSIONS: Mitochondrial content and function were not associated with insulin sensitivity among participants with RA. However, our study demonstrates a significant association between muscle mitochondrial content and physical activity level, highlighting the potential for future exercise interventions that enhance mitochondrial efficiency in RA patients.

The Diagnostic Conundrum of Glomerular Crescents With IgA Deposits.

Introduction: Glomerulonephritis (GN) with crescents and IgA deposits in kidney biopsy poses a frequent diagnostic and therapeutic dilemma because of multiple possibilities. Methods: Native kidney biopsies showing glomerular IgA deposition and crescents (excluding lupus nephritis) were identified from our biopsy archives between 2010 and 2021. Detailed clinicopathologic features were assessed. One-year clinical follow-up on a subset of cases was obtained. Results: A total of 285 cases were identified, and these clustered into IgA nephropathy (IgAN, n = 108), Staphylococcus or other infection-associated GN/infection-related GN (SAGN/IRGN, n = 43), and antineutrophil cytoplasmic antibody-associated GN (ANCA-GN, n = 26) based on a constellation of clinicopathologic features, but 101 cases (group X) could not be definitively differentiated. The reasons have been elucidated, most important being atypical combination of clinicopathologic features and lack of definitive evidence of active infection. Follow-up (on 72/101 cases) revealed that clinicians' working diagnosis was IgAN in 43%, SAGN/IRGN in 22%, ANCA-GN in 28%, and others in 7% of the cases, but treatment approach varied from supportive or antibiotics to immunosuppression in each subgroup. Comparing these cases as "received immunosuppression" versus "non-immunosuppression," only 2 features differed, namely C3-dominant staining, and possibility of recent infection (both higher in the no-immunosuppression group) (P < 0.05). Renal loss was higher in the non-immunosuppression subgroup, but not statistically significant (P = 0.11). Conclusion: Diagnostic overlap may remain unresolved in a substantial number of kidney biopsies with glomerular crescents and IgA deposits. A case-by-case approach, appropriate antibiotics if infection is ongoing, and consideration for cautious immunosuppressive treatment for progressive renal dysfunction may be needed for best chance of renal recovery.