The effectiveness of an osteopathic manual technique compared with a breathing exercise on vagal tone as indicated by heart rate variability, a crossover study.

INTRODUCTION: Parasympathetic nervous system (PSNS) function can be inferred by heart rate variability (HRV) providing indications about an individual's health. Manual therapy may influence PSNS function, however the research outcomes in this regard are equivocal. This study explored the PSNS effect of a measured breathing technique with suboccipital balanced ligamentous tension, an osteopathic manipulative therapy technique. METHODS: Healthy adult participants in this crossover study (n = 18) were randomly allocated into two groups with differing order of interventions. A 1:1 breathing rate of 6 breaths per minute maintained for 5 min was compared to the osteopathic intervention. HRV was measured for 5 min before and after each intervention and analysed using the root mean square of successive differences (RMSSD) between normal heartbeats and high frequency normalised units (HFnu). RESULTS: The RMSSD data demonstrated no significant difference between groups or within groups (p > 0.05) over time. HFnu results showed a significant between-group difference over the four time points (p = 0.004) with a medium effect size (ηp2 = 0.240), and no significant within-group difference (p > 0.05). DISCUSSION: The osteopathic intervention raised HRV to a small extent, however measured breathing lowered HRV. In the group that received the osteopathic technique first, HFnu values continued to rise post-osteopathic treatment possibly indicating an increasing parasympathetic effect over time. Recommendations for future studies include changing the breathing ratio to ensure parasympathetic response, take into account potential delayed effects of interventions, consider outcome measures less variable than HRV, and longer follow up times. CONCLUSION: This study suggests parasympathetic stimulation may occur with the application of suboccipital balanced ligamentous tension and sympathetic stimulation from measured breathing.

Methodological approach to sleep state misperception in insomnia disorder: Comparison between multiple nights of actigraphy recordings and a single night of polysomnography recording.

STUDY OBJECTIVE: To provide a comprehensive assessment of sleep state misperception in insomnia disorder (INS) and good sleepers (GS) by comparing recordings performed for one night in-lab (PSG and night review) and during several nights at-home (actigraphy and sleep diaries). METHODS: Fifty-seven INS and 29 GS wore an actigraphy device and filled a sleep diary for two weeks at-home. They subsequently completed a PSG recording and filled a night review in-lab. Sleep perception index (subjective/objective × 100) of sleep onset latency (SOL), sleep duration (TST) and wake duration (TST) were computed and compared between methods and groups. RESULTS: GS displayed a tendency to overestimate TST and WASO but correctly perceived SOL. The degree of misperception was similar across methods within the GS group. In contrast, INS underestimated their TST and overestimated their SOL both in-lab and at-home, yet the severity of misperception of SOL was larger at-home than in-lab. Finally, INS overestimated WASO only in-lab while correctly perceiving it at-home. While only the degree of TST misperception was stable across methods in INS, misperception of SOL and WASO were dependent on the method used. CONCLUSIONS: We found that GS and INS exhibit opposite patterns and severity of sleep misperception. While the degree of misperception in GS was similar across methods, only sleep duration misperception was reliably detected by both in-lab and at-home methods in INS. Our results highlight that, when assessing sleep misperception in insomnia disorder, the environment and method of data collection should be carefully considered.

The sonographic protocol for the emergent evaluation of aortic dissections (SPEED protocol): A multicenter, prospective, observational study.

OBJECTIVES: An aortic dissection (AoD) is a potentially life-threatening emergency with mortality rates exceeding 50%. While computed tomography angiography remains the diagnostic standard, patients may be too unstable to leave the emergency department. Investigators developed a point-of-care ultrasound (POCUS) protocol combining transthoracic echocardiography (TTE) and the abdominal aorta. The study objective was to determine the test characteristics of this protocol. METHODS: This was an institutional review board-approved, multicenter, prospective, observational, cohort study of a convenience sample of adult patients. Patients suspected of having an AoD received a TTE and abdominal aorta POCUS. Three sonographic signs suggested AoD: a pericardial effusion, an intimal flap, or an aortic outflow track diameter measuring more than 35 mm. Investigators present continuous and categorical data as medians with interquartile ranges or proportions with 95% confidence intervals (CIs) and utilized standard 2 × 2 tables on MedCalc (Version 19.1.6) to calculate test characteristics with 95% CI. RESULTS: Investigators performed 1314 POCUS examinations, diagnosing 21 Stanford type A and 23 Stanford type B AoD. Forty-one of the 44 cases had at least one of the aforementioned sonographic findings. The protocol has a sensitivity of 93.2% (95% CI 81.3-98.6), specificity of 90.9 (95% CI 89.2-92.5), positive and negative predictive values of 26.3% (95% CI 19.6-33.9) and 99.7% (95% CI 99.2-100), respectively, and an accuracy of 91% (95% CI 89.3-92.5). CONCLUSIONS: The SPEED protocol has an overall sensitivity of 93.2% for AoD.

Novel Independent Trans- and Cis-Genetic Variants Associated with CYP2D6 Expression and Activity in Human Livers.

Cytochrome P450 2D6 (CYP2D6) is a critical hepatic drug-metabolizing enzyme in humans, responsible for metabolizing approximately 20%-25% of commonly used medications such as codeine, desipramine, fluvoxamine, paroxetine, and tamoxifen. The CYP2D6 gene is highly polymorphic, resulting in substantial interindividual variability in its catalytic function and the pharmacokinetics and therapeutic outcomes of its substrate drugs. Although many functional CYP2D6 variants have been discovered and validated, a significant portion of the variability in the expression and activity of CYP2D6 remains unexplained. In this study, we performed a genome-wide association study (GWAS) to identify novel variants associated with CYP2D6 protein expression in individual human livers, followed by a conditional analysis to control for the effect of functional CYP2D6 star alleles. We also examined their impact on hepatic CYP2D6 activity. Genotyping on a genome-wide scale was achieved using the Illumina Multi-Ethnic Genotyping Array (MEGA). A data-independent acquisition (DIA)-based proteomics method was used to quantify CYP2D6 protein concentrations. CYP2D6 activity was determined by measuring the dextromethorphan O-demethylation in individual human liver s9 fractions. The GWAS identified 44 single nuclear polymorphisms (SNPs) that are significantly associated with CYP2D6 protein expressions with a P value threshold of 5.0 × 10-7 After the conditional analysis, five SNPs, including the cis-variants rs1807493 and rs1062753 and the trans-variants rs4073010, rs729559, and rs80274432, emerged as independent variants significantly correlated with hepatic CYP2D6 protein expressions. Notably, four of these SNPs, except for rs80274432, also exhibited a significant association with CYP2D6 activities in human livers, suggesting their potential as novel and independent cis- and trans-variants regulating CYP2D6. SIGNIFICANT STATEMENT: Using individual human livers, we identified four novel cis- and trans-pQTLs/aQTLs (protein quantitative trait loci/activity quantitative trait loci) of Cytochrome P450 2D6 (CYP2D6) that are independent from known functional CYP2D6 star alleles. This study connects the CYP2D6 gene expression and activity, enhancing our understanding of the genetic variants associated with CYP2D6 protein expression and activity, potentially advancing our insight into the interindividual variability in CYP2D6 substrate medication response.

Temminck pangolins relax the precision of body temperature regulation when resources are scarce in a semi-arid environment.

Climate change is impacting mammals both directly (for example, through increased heat) and indirectly (for example, through altered food resources). Understanding the physiological and behavioural responses of mammals in already hot and dry environments to fluctuations in the climate and food availability allows for a better understanding of how they will cope with a rapidly changing climate. We measured the body temperature of seven Temminck's pangolins (Smutsia temminckii) in the semi-arid Kalahari for periods of between 4 months and 2 years. Pangolins regulated body temperature within a narrow range (34-36°C) over the 24-h cycle when food (and hence water, obtained from their prey) was abundant. When food resources were scarce, body temperature was regulated less precisely, 24-h minimum body temperatures were lower and the pangolins became more diurnally active, particularly during winter when prey was least available. The shift toward diurnal activity exposed pangolins to higher environmental heat loads, resulting in higher 24-h maximum body temperatures. Biologging of body temperature to detect heterothermy, or estimating food abundance (using pitfall trapping to monitor ant and termite availability), therefore provide tools to assess the welfare of this elusive but threatened mammal. Although the physiological and behavioural responses of pangolins buffered them against food scarcity during our study, whether this flexibility will be sufficient to allow them to cope with further reductions in food availability likely with climate change is unknown.

Gallstone Ileus: A Case Report in a 74-Year-Old Male.

Gallstone ileus is a rare complication of complicated gallbladder disease. Typically the result of a cholecystocholeduodenal fistula, a gallstone enters the small bowel and impacts in the ileum causing an obstruction. In this case study, a 74-year-old male presented to the emergency department with nausea, vomiting, and constipation for 2 weeks. CT revealed pneumobilia and a 3.1 cm calcified mass in the terminal ileum. The patient was successfully treated with a robotic-assisted enterotomy alone without complications.

An α7 nAChR approach for the baseline-dependent modulation of deviance detection in schizophrenia: A pilot study assessing the combined effect of CDP-choline and galantamine.

BACKGROUND: Cognitive operations including pre-attentive sensory processing are markedly impaired in patients with schizophrenia (SCZ) but evidence significant interindividual heterogeneity, which moderates treatment response with nicotinic acetylcholine receptor (nAChR) agonists. Previous studies in healthy volunteers have shown baseline-dependency effects of the α7 nAChR agonist cytidine 5'-diphosphocholine (CDP-choline) administered alone and in combination with a nicotinic allosteric modulator (galantamine) on auditory deviance detection measured with the mismatch negativity (MMN) event-related potential (ERP). AIM: The objective of this pilot study was to assess the acute effect of this combined α7 nAChR-targeted treatment (CDP-choline/galantamine) on speech MMN in patients with SCZ (N = 24) stratified by baseline MMN responses into low, medium, and high baseline auditory deviance detection subgroups. METHODS: Patients with a stable diagnosis of SCZ attended two randomized, double-blind, placebo-controlled and counter-balanced testing sessions where they received a placebo or a CDP-choline (500 mg) and galantamine (16 mg) treatment. MMN ERPs were recorded during the presentation of a fast multi-feature speech MMN paradigm including five speech deviants. Clinical measures were acquired before and after treatment administration. RESULTS: While no main treatment effect was observed, CDP-choline/galantamine significantly increased MMN amplitudes to frequency, duration, and vowel speech deviants in low group individuals. Individuals with higher positive and negative symptom scale negative, general, and total scores expressed the greatest MMN amplitude improvement following CDP-choline/galantamine. CONCLUSIONS: These baseline-dependent nicotinic effects on early auditory information processing warrant different dosage and repeated administration assessments in patients with low baseline deviance detection levels.

Sleep strengthens resting-state functional communication between brain areas involved in the consolidation of problem-solving skills.

Sleep consolidates procedural memory for motor skills, and this process is associated with strengthened functional connectivity in hippocampal-striatal-cortical areas. It is unknown whether similar processes occur for procedural memory that requires cognitive strategies needed for problem-solving. It is also unclear whether a full night of sleep is indeed necessary for consolidation to occur, compared with a daytime nap. We examined how resting-state functional connectivity within the hippocampal-striatal-cortical network differs after offline consolidation intervals of sleep, nap, or wake. Resting-state fMRI data were acquired immediately before and after training on a procedural problem-solving task that requires the acquisition of a novel cognitive strategy and immediately prior to the retest period (i.e., following the consolidation interval). ROI to ROI and seed to whole-brain functional connectivity analyses both specifically and consistently demonstrated strengthened hippocampal-prefrontal functional connectivity following a period of sleep versus wake. These results were associated with task-related gains in behavioral performance. Changes in functional communication were also observed between groups using the striatum as a seed. Here, we demonstrate that at the behavioral level, procedural strategies benefit from both a nap and a night of sleep. However, a full night of sleep is associated with enhanced functional communication between regions that support problem-solving skills.

Inpatient COVID-19 vaccination rollout: Improving access to vaccination.

BACKGROUND: We were aware of high numbers of inpatients unvaccinated against COVID-19 at Guy's and St Thomas' NHS Foundation Trust (GSTT). Due to this, an inpatient vaccination protocol was set up in July 2021, with initially limited uptake. METHODS: From October 2021, a multidisciplinary team worked to improve the protocol for inpatient vaccination, with the development of a system that gave ownership to clinical teams. RESULTS: In 4 months (July 2021 to November 2021), 20 inpatients had been vaccinated at GSTT. Following our intervention, rates of uptake increased, and 34 patients were vaccinated in less than 2 months (November 2021 to January 2022). Forty-five patients who had been referred were discharged without vaccination; attempts were made to invite them to receive a vaccine. CONCLUSION: An improved pathway and referral process increased the number of inpatient vaccinations delivered. Further work is required in order to ensure that more patients who have been referred are vaccinated.

Comparing two machine learning approaches in predicting lupus hospitalization using longitudinal data.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by flares ranging from mild to life-threatening. Severe flares and complications can require hospitalizations, which account for most of the direct costs of SLE care. This study investigates two machine learning approaches in predicting SLE hospitalizations using longitudinal data from 925 patients enrolled in a multicenter electronic health record (EHR)-based lupus cohort. Our first Differential approach accounts for the time dependencies in sequential data by introducing additional lagged variables between consecutive time steps. We next evaluate the performance of LSTM, a state-of-the-art deep learning model designed for time series. Our experimental results demonstrate that both methods can effectively predict lupus hospitalizations, but each has its strengths and limitations. Specifically, the Differential approach can be integrated into any non-temporal machine learning algorithms and is preferred for tasks with short observation periods. On the contrary, the LSTM model is desirable for studies utilizing long observation intervals attributing to its capability in capturing long-term dependencies embedded in the longitudinal data. Furthermore, the Differential approach has more options in handling class imbalance in the underlying data and delivers stable performance across different prognostic horizons. LSTM, on the other hand, demands more class-balanced training data and outperforms the Differential approach when there are sufficient positive samples facilitating model training. Capitalizing on our experimental results, we further study the optimal length of patient monitoring periods for different prediction horizons.

The costs of replacing coal plant jobs with local instead of distant wind and solar jobs across the United States.

To further a just energy transition, jobs lost at retiring coal plants could be replaced by jobs at wind and solar plants. No research quantifies the feasibility and costs of such an undertaking across the United States. Complicating such an undertaking are workers' place-based preferences that could prevent them from moving long distances, e.g. to high renewable resource regions. We formulate a bottom-up optimization model to quantify the technical feasibility and costs of replacing coal plant jobs with local versus distant jobs in the renewables sector. For the contiguous United States, we find replacing coal generation and employment with local wind and solar investments is feasible. Siting renewables local to instead of distant from retiring coal plants increases replacement costs by 5%-33% across sub-national regions and by $83 billion, or 24%, across the United States. These costs are modest relative to overall energy transition costs.

Operative Rib Fixation at a Rural Trauma Center.

INTRODUCTION: Operative rib fixation is becoming more common in the management of rib fractures, with studies showing benefits of surgery in decreasing time on mechanical ventilation, ICU and total hospital length of stay, and mortality. This paper will review the data from our institution to determine if these benefits were seen in our trauma population. METHODS: A retrospective review of the institution's trauma database was conducted, including operative patients (n = 36), control patients (nonoperative patients from October 2018 to October 2019, n = 207), and selected control patients based on similar injury severity score range as operative patients (n = 181). Data reviewed included time on mechanical ventilation, ICU and total hospital length of stay, and disposition at discharge, including mortalities. Operative complications were also reviewed. RESULTS: The operative group had a higher ISS compared to both controls, longer average time on mechanical ventilation, longer average ICU and total hospital length of stay, and a higher percentage of patients discharged to inpatient facilities. However, the operative group had lower mortality compared to the control groups. The operative group had 3 surgical site infections requiring readmission and hardware removal. DISCUSSION: Unlike other studies, our operative patients did not see improvements in time on mechanical ventilation, ICU and total hospital length of stay, or disposition at discharge, but did see a mortality benefit. Confounding factors include higher average ISS in the operative group, and over-sedation in the ICU. Data collection is ongoing, and refinements are being made to perioperative and ICU management to minimize these confounding variables.

Exploration of machine learning methods to predict systemic lupus erythematosus hospitalizations.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a heterogeneous disease characterized by disease flares which can require hospitalization. Our objective was to apply machine learning methods to predict hospitalizations for SLE from electronic health record (EHR) data. METHODS: We identified patients with SLE in a longitudinal EHR-based cohort with ≥2 outpatient rheumatology visits between 2012 and 2019. We applied multiple machine learning methods to predict hospitalizations with a primary diagnosis code for SLE, including decision tree, random forest, naive Bayes, logistic regression, and an ensemble method. Candidate predictors were derived from structured EHR features, including demographics, laboratory tests, medications, ICD-9/10 codes for SLE manifestations, and healthcare utilization. We used two approaches to assess these variables over longitudinal follow-up, including the incorporation of lagged features to capture changes over time of clinical data. The performance of each model was evaluated by overall accuracy, the F statistic, and the area under the receiver operator curve (AUC). RESULTS: We identified 1996 patients with SLE. 4.6% were hospitalized for SLE in their most recent year of follow-up. Random forest models had highest performance in predicting SLE hospitalizations, with AUC 0.751 and AUC 0.772 for two approaches (averaging and progressive), respectively. The leading predictors of SLE hospitalizations included dsDNA positivity, C3 level, blood cell counts, and inflammatory markers as well as age and albumin. CONCLUSION: We have demonstrated that machine learning methods can predict SLE hospitalizations. We identified key predictors of these events including known markers of SLE disease activity; further validation in external cohorts is warranted.

Effects of cognitive behavioral therapy for insomnia on subjective and objective measures of sleep and cognition.

STUDY OBJECTIVES: To assess the effects of Cognitive Behavioral Therapy for insomnia (CBTi) on subjective and objective measures of sleep, sleep-state misperception and cognitive performance. METHODS: We performed a randomized-controlled trial with a treatment group and a wait-list control group to assess changes in insomnia symptoms after CBTi (8 weekly group sessions/3 months) in 62 participants with chronic insomnia. To this end, we conducted a multimodal investigation of sleep and cognition including subjective measures of sleep difficulties (Insomnia Severity Index [ISI]; sleep diaries) and cognitive functioning (Sahlgrenska Academy Self-reported Cognitive Impairment Questionnaire), objective assessments of sleep (polysomnography recording), cognition (attention and working memory tasks), and sleep-state misperception measures, collected at baseline and at 3-months post-randomization. We also assessed ISI one year after CBTi. Our main analysis investigated changes in sleep and cognition after 3 months (treatment versus wait-list). RESULTS: While insomnia severity decreased and self-reported sleep satisfaction improved after CBTi, we did not find any significant change in objective and subjective sleep measures (e.g., latency, duration). Degree of discrepancy between subjective and objective sleep (i.e., sleep misperception) in sleep latency and sleep duration decreased after CBTi suggesting a better perception of sleep after CBTi. In contrast, both objective and subjective cognitive functioning did not improve after CBTi. CONCLUSIONS: We showed that group-CBTi has a beneficial effect on variables pertaining to the subjective perception of sleep, which is a central feature of insomnia. However, we observed no effect of CBTi on measures of cognitive functioning.

Competing Risk Analysis of Time to Communal Residence for Elder Orphans.

Elder Orphans, socially/physically isolated older adults without caregiving support, are of interest in an aging population. Lack of caregivers for Elder Orphans may influence relocation to residential care facilities, including skilled nursing or assisted living facilities, compared to aging in place. Using the National Health and Aging Trends Study (NHATS), Competing Risk Survival Analyses were performed to determine if Elder Orphans or those At Risk for becoming elder orphans had increased risk for residential care relocation over nine NHATS waves (2011-2019). Elder Orphans had significantly higher risk for moving to residential care facilities in unadjusted (SHR = 1.780; p = 0.001) and adjusted (SHR = 1.571; p = 0.043) models. Those At Risk for becoming an elder orphan had significantly decreased risk for residential care residence in unadjusted (SHR = 0.517; p < 0.001) and adjusted (SHR = 0.726; p = 0.037) models. As aging in place becomes prioritized in the US healthcare system, understanding caregiving needs of older adults is vital to their health outcomes.

Postoperative Fluid Collections in Total Joint Arthroplasty: A Narrative Review.

A post-operative fluid collection (POFC) represents a common finding in both primary and revision total joint arthroplasty (TJA). Fortunately, most resolve on their own, but in instances where they become symptomatic, prompt identification and management are paramount, especially when they occur adjacent to a joint arthroplasty because of the increased the risk of developing a periprosthetic joint infection. A strong clinical suspicion with appropriate clinical exam is required along with select imaging modalities to arrive at a diagnosis. Meticulous surgical technique is crucial to prevent POFC, but new emerging treatments continue to evolve. This article presents an updated overview of incidence, pathophysiology, diagnosis, and management of POFC in the setting of TJA. We review the role of select imaging modalities as well as summarize current literature regarding new treatments such as sclerotherapy agents, acellular dermal matrices, and negative pressure wound therapy. Future studies are necessary to explore the interplay of inflammatory mediators in POFC formation and to define their role in fluid collection resolution.

Functional differences in cerebral activation between slow wave-coupled and uncoupled sleep spindles.

Spindles are often temporally coupled to slow waves (SW). These SW-spindle complexes have been implicated in memory consolidation that involves transfer of information from the hippocampus to the neocortex. However, spindles and SW, which are characteristic of NREM sleep, can occur as part of this complex, or in isolation. It is not clear whether dissociable parts of the brain are recruited when coupled to SW vs. when spindles or SW occur in isolation. Here, we tested differences in cerebral activation time-locked to uncoupled spindles, uncoupled SW and coupled SW-spindle complexes using simultaneous EEG-fMRI. Consistent with the "active system model," we hypothesized that brain activations time-locked to coupled SW-spindles would preferentially occur in brain areas known to be critical for sleep-dependent memory consolidation. Our results show that coupled spindles and uncoupled spindles recruit distinct parts of the brain. Specifically, we found that hippocampal activation during sleep is not uniquely related to spindles. Rather, this process is primarily driven by SWs and SW-spindle coupling. In addition, we show that SW-spindle coupling is critical in the activation of the putamen. Importantly, SW-spindle coupling specifically recruited frontal areas in comparison to uncoupled spindles, which may be critical for the hippocampal-neocortical dialogue that preferentially occurs during sleep.

Teaching undergraduate physical chemistry lab with kinetic analysis of COVID-19 in the United States.

A physical chemistry lab for undergraduate students described in this report is about applying kinetic models to analyze the spread of COVID-19 in the United States and obtain the reproduction numbers. The susceptible-infectious-recovery (SIR) model and the SIR-vaccinated (SIRV) model are explained to the students and are used to analyze the COVID-19 spread data from U.S. Centers for Disease Control and Prevention (CDC). The basic reproduction number R 0 and the real-time reproduction number R t of COVID-19 are extracted by fitting the data with the models, which explains the spreading kinetics and provides a prediction of the spreading trend in a given state. The procedure outlined here shows the differences between the SIR model and the SIRV model. The SIRV model considers the effect of vaccination which helps explain the later stages of the ongoing pandemic. The predictive power of the models is also shown giving the students some certainty in the predictions they made for the following months.

Elevated C-Reactive Protein in Alzheimer's Disease Without Depression in Older Adults: Findings From the Health and Retirement Study.

We examined the association between differential diagnoses of major stroke and probable Alzheimer's disease (AD) and mixed AD on C-reactive protein (CRP) in older adults with and without depression. Secondary data analyses examined associations between blood-based measures of probable peripheral inflammation using CRP collected from dried blood spots in the Health and Retirement Study, a nationally representative sample of individuals aged 50 and older. A validated pattern-recognition algorithm was utilized to identify cognitive decline indicative of probable AD, mixed AD, and major stroke. Negative binomial regressions were utilized to model concentrations of serologic CRP. On average, participants (N = 4 601) were 70 years old, female, and non-Hispanic White. Mixed AD participants had a 0.26 mg/dL increase in CRP compared to unimpaired participants, controlling for demographics, health behaviors, and comorbidities. Those with mixed AD had 2.14 times increased odds of having high CRP (odds ratio = 2.14 [1.19-3.85]). In analyses stratified by depression, adults with mixed AD and without depression had an additional 0.37 mg/dL increase in CRP (SE = 0.06; p < .001) compared to unimpaired adults. Those with AD without depression had a 0.20 mg/dL increase in CRP (SE = 0.07; p < .01). Age was not associated with increased CRP in nondepressed older adults. Depressed adults with major stroke had a -0.26 mg/dL decrease in CRP (SE = 0.11; p = .02), controlling for hypertension, alcoholic drinks/beverages per week, and smoking status. Concentration modeling revealed that participants with major stroke, probable AD, and probable mixed AD without depression had significantly higher CRP concentrations when compared to unimpaired older adults.