Exercise does not cause post-exertional malaise in Veterans with Gulf War Illness: A randomized, controlled, dose-response, crossover study.

Chronic multisymptom illnesses (CMI) such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, Long-COVID, and Gulf War Illness (GWI) are associated with an elevated risk of post-exertional malaise (PEM), an acute exacerbation of symptoms and other related outcomes following exercise. These individuals may benefit from personalized exercise prescriptions which prioritize risk minimization, necessitating a better understanding of dose-response effects of exercise intensity on PEM. METHODS: Veterans with GWI (n = 40) completed a randomized controlled crossover experiment comparing 20 min of seated rest to light-, moderate-, and vigorous-intensity cycling conditions over four separate study visits. Symptoms, pain sensitivity, cognitive performance, inflammatory markers (C-reactive protein and plasma cytokines) were measured before and within 1 h after exercise and seated rest. Physical activity behavior was measured ≥ 7 days following each study visit via actigraphy. Linear mixed effects regression models tested the central hypothesis that higher intensity exercise would elicit greater exacerbation of negative outcomes, as indicated by a significant condition-by-time interaction for symptom, pain sensitivity, cognitive performance, and inflammatory marker models and a significant main effect of condition for physical activity models. RESULTS: Significant condition-by-time interactions were not observed for primary or secondary measures of symptoms, pain sensitivity, cognitive performance, and a majority of inflammatory markers. Similarly, a significant effect of condition was not observed for primary or secondary measures of physical activity. CONCLUSIONS: Undesirable effects such as symptom exacerbation were observed for some participants, but the group-level risk of PEM following light-, moderate-, or vigorous-intensity exercise was no greater than seated rest. These findings challenge several prior views about PEM and lend support to a broader body of literature showing that the benefits of exercise outweigh the risks.

Exercise as Medicine for People with a Substance Use Disorder: An ACSM Call to Action Statement.

ABSTRACT: Over 20 million Americans are living with a substance use disorder (SUD) and nearly 100,000 die annually from drug overdoses, with a majority involving an opioid. Many people with SUD have co-occurring chronic pain and/or a mental health disorder. Exercise is a frontline treatment for chronic pain and is an effective strategy for reducing depression and anxiety and improving overall mental health. Several studies have shown that exercise improves SUD-related outcomes including abstinence; however, there is limited large-scale randomized clinical trial evidence to inform integration of exercise into practice. In this Call to Action, we aim to raise awareness of the specific issues that should be addressed to advance exercise as medicine in people with SUD including the challenges of co-occurring chronic pain, mental illness, and cardiopulmonary health conditions. In addition, specialized training for exercise professionals and other support staff should be provided on these issues, as well as on the multiple dimensions of stigma that can impair engagement in treatment and overall recovery in people with SUD.

Pain, but not Physical Activity, is Associated with Gray Matter Volume Differences in Gulf War Veterans with Chronic Pain.

Chronic musculoskeletal pain (CMP) is a significant burden for Persian Gulf War Veterans (GWV), yet the causes are poorly understood. Brain structure abnormalities are observed in GWV, however relationships with modifiable lifestyle factors such as physical activity (PA) are unknown. We evaluated gray matter volumes and associations with symptoms, PA, and sedentary time in GWV with and without CMP. Ninety-eight GWV (10 females) with CMP and 56 GWV (7 females) controls completed T1 weighted magnetic resonance imaging, pain and fatigue symptom questionnaires, and PA measurement via actigraphy. Regional gray matter volumes were analyzed using voxel-based morphometry and were compared across groups using analysis of covariance. Separate multiple linear regression models were used to test associations between PA intensities, sedentary time, symptoms, and gray matter volumes. Family-wise cluster error rates were used to control for multiple comparisons (α=0.05). GWV with CMP reported greater pain and fatigue symptoms, worse mood, and engaged in less moderate-to-vigorous PA and more sedentary time than healthy GWV (all p<0.05). GWV with CMP had smaller gray matter volumes in the bilateral insula and larger volumes in the frontal pole (p<0.05adjusted). Gray matter volumes in the left insula were associated with pain symptoms (rpartial=0.26, -0.29; p<0.05adjusted). No significant associations were observed for either PA or sedentary time (p>0.05adjusted). GWV with CMP had smaller gray matter volumes within a critical brain region of the descending pain processing network and larger volumes within brain regions associated with pain sensation and affective processing which may reflect pain chronification.Significance Statement:The pathophysiology of chronic pain in Gulf War Veterans is understudied and not well understood. In a large sample of Gulf War Veterans, we report Veterans with chronic musculoskeletal pain have smaller gray matter volumes in brain regions associated with pain regulation and larger volumes in regions associated with pain sensitivity compared to otherwise healthy Gulf War Veterans. Gray matter volumes in regions of pain regulation were significantly associated with pain symptoms and encompassed the observed group brain volume differences. These results are suggestive of deficient pain modulation that may contribute to pain chronification.

Pain-Related Post-Exertional Malaise in Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia: A Systematic Review and Three-Level Meta-Analysis.

OBJECTIVE: Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are two debilitating, moderately comorbid illnesses in which chronic musculoskeletal pain symptoms are prevalent. These individuals can experience post-exertional malaise (PEM), a phenomenon in which symptom severity is worsened for 24 hours or longer after physical stress, but the pain-related component of PEM is not well characterized. DESIGN: Systematic review and meta-analysis. METHODS: Case-control studies involving adults with ME/CFS or FM and measuring pain symptoms before and after exposure to a standardized aerobic exercise test were included. Hedges' d effect sizes were aggregated with random-effects models, and potential moderators were explored with meta-regression analysis. Results were adjusted for nesting effects with three-level modeling. RESULTS: Forty-five effects were extracted from 15 studies involving 306 patients and 292 healthy controls. After adjusting for nesting effects, we observed a small to moderate effect indicating higher post-exercise pain in patients than in controls (Hedges' d = 0.42; 95% confidence interval [CI]: 0.16-0.67). The mean effect was significantly moderated by pain measurement time point (b = -0.19, z = -2.57, P = 0.01), such that studies measuring pain 8-72 hours after exercise showed larger effects (d = 0.71, 95% CI = 0.28-1.14) than did those measuring pain 0-2 hours after exercise (d = 0.32, 95% CI = 0.10-0.53). CONCLUSIONS: People with ME/CFS and FM experience small to moderate increases in pain severity after exercise, which confirms pain as a component of PEM and emphasizes its debilitating impact in ME/CFS and FM. Future directions include determining mechanisms of pain-related PEM and developing exercise prescriptions that minimize symptom exacerbation in these illnesses.

Transcranial Color-Coded Doppler Cerebral Hemodynamics Following Aerobic Exercise Training: Outcomes From a Pilot Randomized Clinical Trial.

Introduction: An active lifestyle with regular exercise is thought to decrease or delay the onset of Alzheimer dementia through increasing blood flow to the brain. We examined the mean flow velocity (MFV) and pulsatility index (PI) in the middle cerebral arteries of individuals randomized into two groups-a Usual Physical Activity (UPA) group and an Enhanced Physical Activity (EPA) exercise intervention group-to determine if exercise training is related to changes in cerebral blood flow. Methods: We examined 23 participants, randomized into a UPA group (n=12) and an EPA group (n=11), with transcranial color-coded Doppler (TCCD) and cardiorespiratory fitness (VO2peak, mL/kg/min) testing at baseline and following a 26-week intervention. TCCD was used to measure MFV and PI. Participants in the EPA group completed supervised aerobic exercise training for 26 weeks. Kendall's tau b correlation was used to examine relationships between variables. The Wilcoxon Rank Sum tests were used to examine changes between the UPA and EPA groups. Results: There was no significant change in MFV or PI in the UPA group or the EPA group (p-values >0.05) between baseline and 26 weeks; the change between the UPA and EPA groups was also not significant (p=0.603). There was no evidence of an association between change in VO2peak and change in MFV or PI (all p-values >0.05). Participants in the EPA group significantly increased their VO2peak compared to the UPA group (p=0.027). Conclusion: This study did not demonstrate evidence of a significant change in the MFV in the middle cerebral arteries or evidence of a significant change in the PI between UPA and EPA groups. Future studies should be performed in larger cohorts and should consider use of personalized exercise programs to maximize understanding of how cerebrovascular hemodynamics change in structure and function with exercise for adults at risk for Alzheimer dementia.

Utility of Water Siphon Maneuver for Eliciting Gastroesophageal Reflux During Barium Esophagography: Correlation With Histologic Findings.

OBJECTIVE: The objective of this study is to evaluate whether the water siphon maneuver improves detection of gastroesophageal (GE) reflux during barium esophagography compared with observation for spontaneous reflux only. Histopathologic analysis is the reference standard. MATERIALS AND METHODS: This retrospective study assessed 87 outpatients who underwent both barium esophagography and upper endoscopy-guided biopsy within a 30-day interval. The water siphon maneuver was routinely performed when spontaneous GE reflux was not observed during the fluoroscopic study. Radiology reports were reviewed for mentions of the presence of reflux and the circumstances in which it was observed (as a spontaneous occurrence or as a result of the water siphon maneuver). Pathology reports from subsequent endoscopic biopsies were reviewed to identify histologic changes of reflux disease. The sensitivity, specificity, and accuracy of esophagography, observation for spontaneous reflux, and the water siphon maneuver were calculated and then compared using a McNemar test. RESULTS: Of the 87 patients, 57 (65.5%) had GE reflux diagnosed on the basis of histologic changes noted on endoscopy, and 30 (34.5%) did not. A total of 57 patients (65.5%) showed reflux during esophagography, 41 (71.9%) of whom had reflux diagnosed by the water siphon maneuver, and 16 (28.1%) had reflux diagnosed on the basis of observation of spontaneous reflux. Forty-four patients had reflux diagnosed on the basis of both a barium study and histologic findings; 13 patients had reflux noted on esophagography but had negative histologic findings. The overall sensitivity, specificity, and accuracy of esophagography for reflux were 77.2%, 56.7%, and 70.1%, respectively. Spontaneous reflux alone had a sensitivity, specificity, and accuracy of 21.1%, 86.7%, and 43.7%, respectively. The water siphon maneuver showed a sensitivity of 71.1%, a specificity of 65.4%, and accuracy of 69.0%. The differences in the sensitivity, specificity, and accuracy of the water siphon maneuver versus observation of spontaneous reflux were statistically significant (p ≤ 0.004). CONCLUSION: A properly performed and interpreted water siphon maneuver significantly increases the sensitivity and accuracy for GE reflux during esophagography, compared with observation for spontaneous reflux alone. The water siphon maneuver is a simple addition to barium esophagography that improves sensitivity and accuracy for the diagnosis of GE reflux compared with observation alone.

Catastrophizing Interferes with Cognitive Modulation of Pain in Women with Fibromyalgia.

Background: Pain modulation is a critical function of the nociceptive system that includes the ability to engage descending pain control systems to maintain a functional balance between facilitation and inhibition of incoming sensory stimuli. Dysfunctional pain modulation is associated with increased risk for chronic pain and is characteristic of fibromyalgia (FM). Catastrophizing is also common in FM. However, its influence on pain modulation is poorly understood. Objective: To determine the role of catastrophizing on central nervous system processing during pain modulation in FM via examining brain responses and pain sensitivity during an attention-distraction paradigm. Methods: Twenty FM patients and 18 healthy controls (CO) underwent functional magnetic resonance imaging while receiving pain stimuli, administered alone and during distracting cognitive tasks. Pain ratings were assessed after each stimulus. Catastrophizing was assessed with the Pain Catastrophizing Scale (PCS). Results: The ability to modulate pain during distraction varied among FM patients and was associated with catastrophizing. This was demonstrated by significant positive relationships between PCS scores and pain ratings (P < 0.05) and brain responses in the dorsolateral prefrontal cortex (P < 0.01). Relationships between catastrophizing and pain modulation did not differ between FM and CO (P > 0.05). Conclusions: FM patients with higher levels of catastrophizing were less able to distract themselves from pain, indicative of catastrophizing-related impairments in pain modulation. These results suggest that the tendency to catastrophize interacts with attention-resource allocation and may represent a mechanism of chronic pain exacerbation and/or maintenance. Reducing catastrophizing may improve FM symptoms via improving central nervous system regulation of pain.

Greater fear of reinjury is related to stiffened jump-landing biomechanics and muscle activation in women after ACL reconstruction.

PURPOSE: Fear of reinjury is an important factor in determining who returns to sport following anterior cruciate ligament reconstruction (ACLR). Evidence from other musculoskeletal injuries indicates fear of reinjury may be related to stiffened movement patterns observed in individuals following ACLR. The relationship between fear of reinjury and performance on dynamic tasks, however, has not been investigated. Therefore, the purpose of this study was to investigate the relationship between fear of reinjury and jump-landing biomechanics. METHODS: Thirty-six females (height = 168.7 ± 6.5 cm, body mass = 67.2 ± 10.0 kg, age = 18.9 ± 1.5 years) with a history of ACLR (time from surgery = 26.1 ± 13.3 months) participated in the study. Each participant performed five trials of a standard jump-landing task. 3D motion capture and surface electromyography was used to record peak kinematics and lower extremity muscle activation on the injured limb during the jump landings. Spearman's rank correlations established the relationship between TSK-11 scores and each biomechanical variable of interest. RESULTS: There was a significant, negative relationship between fear of reinjury (TSK-11: 19.9 ± 4.5) and knee (p = 0.006), hip (p = 0.003), and trunk flexion (p = 0.013). There was also a significant, positive relationship between hip adduction (p = 0.007), and gluteus maximus preparatory activation (p = 0.001). CONCLUSIONS: The results of this study indicate that higher fear of reinjury is associated with stiffened movement patterns that are associated with increased risk of a second ACL injury. Similar movement patterns have been observed in patients with low back pain. Clinicians should evaluate psychological and emotional consequences of injury in addition to the physical consequences as they appear to be related. LEVEL OF EVIDENCE: III.

Recognition of the Component Odors in Mixtures.

Natural olfactory stimuli are volatile-chemical mixtures in which relative perceptual saliencies determine which odor-components are identified. Odor identification also depends on rapid selective adaptation, as shown for 4 odor stimuli in an earlier experimental simulation of natural conditions. Adapt-test pairs of mixtures of water-soluble, distinct odor stimuli with chemical features in common were studied. Identification decreased for adapted components but increased for unadapted mixture-suppressed components, showing compound identities were retained, not degraded to individual molecular features. Four additional odor stimuli, 1 with 2 perceptible odor notes, and an added "water-adapted" control tested whether this finding would generalize to other 4-compound sets. Selective adaptation of mixtures of the compounds (odors): 3 mM benzaldehyde (cherry), 5 mM maltol (caramel), 1 mM guaiacol (smoke), and 4 mM methyl anthranilate (grape-smoke) again reciprocally unmasked odors of mixture-suppressed components in 2-, 3-, and 4-component mixtures with 2 exceptions. The cherry note of "benzaldehyde" (itself) and the shared note of "methyl anthranilate and guaiacol" (together) were more readily identified. The pervasive mixture-component dominance and dynamic perceptual salience may be mediated through peripheral adaptation and central mutual inhibition of neural responses. Originating in individual olfactory receptor variants, it limits odor identification and provides analytic properties for momentary recognition of a few remaining mixture-components.

Neural consequences of post-exertion malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Post exertion malaise is one of the most debilitating aspects of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, yet the neurobiological consequences are largely unexplored. The objective of the study was to determine the neural consequences of acute exercise using functional brain imaging. Fifteen female Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients and 15 healthy female controls completed 30min of submaximal exercise (70% of peak heart rate) on a cycle ergometer. Symptom assessments (e.g. fatigue, pain, mood) and brain imaging data were collected one week prior to and 24h following exercise. Functional brain images were obtained during performance of: 1) a fatiguing cognitive task - the Paced Auditory Serial Addition Task, 2) a non-fatiguing cognitive task - simple number recognition, and 3) a non-fatiguing motor task - finger tapping. Symptom and exercise data were analyzed using independent samples t-tests. Cognitive performance data were analyzed using mixed-model analysis of variance with repeated measures. Brain responses to fatiguing and non-fatiguing tasks were analyzed using linear mixed effects with cluster-wise (101-voxels) alpha of 0.05. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients reported large symptom changes compared to controls (effect size ≥0.8, p<0.05). Patients and controls had similar physiological responses to exercise (p>0.05). However, patients exercised at significantly lower Watts and reported greater exertion and leg muscle pain (p<0.05). For cognitive performance, a significant Group by Time interaction (p<0.05), demonstrated pre- to post-exercise improvements for controls and worsening for patients. Brain responses to finger tapping did not differ between groups at either time point. During number recognition, controls exhibited greater brain activity (p<0.05) in the posterior cingulate cortex, but only for the pre-exercise scan. For the Paced Serial Auditory Addition Task, there was a significant Group by Time interaction (p<0.05) with patients exhibiting increased brain activity from pre- to post-exercise compared to controls bilaterally for inferior and superior parietal and cingulate cortices. Changes in brain activity were significantly related to symptoms for patients (p<0.05). Acute exercise exacerbated symptoms, impaired cognitive performance and affected brain function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients. These converging results, linking symptom exacerbation with brain function, provide objective evidence of the detrimental neurophysiological effects of post-exertion malaise.

Psychosocial Influences on Exercise-Induced Hypoalgesia.

Objective: The purpose of this study was to examine psychosocial influences on exercise-induced hypoalgesia (EIH). Design: Randomized controlled trial. Setting: Clinical research unit in a hospital. Subjects: Fifty-eight healthy men and women (mean age = 21 ± 3 years) participated in this study. Methods: Participants were first asked to complete a series of baseline demographic and psychological questionnaires including the Pain Catastrophizing Scale, the Fear of Pain Questionnaire, and the Family Environment Scale. Following this, they were familiarized with both temporal summation of heat pain and pressure pain testing protocols. During their next session, participants completed the Profile of Mood States, rated the intensity of heat pulses, and indicated their pressure pain thresholds and ratings before and after three minutes of submaximal, isometric exercise. Situational catastrophizing was assessed at the end of the experimental session. Results: Results indicated that experimental pain sensitivity was significantly reduced after exercise ( P < 0.05). Men and women did not differ on any of the measured psychosocial variables ( P > 0.05). Positive family environments predicted attenuated pain sensitivity and greater EIH, whereas negative and chronic pain-present family environments predicted worse pain and EIH outcomes. Situational catastrophizing and negative mood state also predicted worse pain and EIH outcomes and were additionally associated with increased ratings of perceived exertion and muscle pain during exercise. Conclusions: This study provides preliminary evidence that psychosocial variables, such as the family environment and mood states, can affect both pain sensitivity and the ability to modulate pain through exercise-induced hypoalgesia.

The role of oxidative stress in premalignant lesions.

PURPOSE OF INVESTIGATION: The authors aimed to evaluate serum total oxidant status (TOS), total antioxidant status (TAS), and oxida- tive stress index (OSI) in women with abnormal cervical cytology, to determine the association between serum oxidant and antioxidant status of these women, and the progression of abnormal cervical cytology. MATERIALS AND METHODS: A total of 75 women enrolled in the study: 20 women with a determination of atypical squamous cells of undetermined significance (ASCUS), 20 women with low squamous intraepithelial lesions (LSIL), 15 women with high squamous intraepithelial lesions (HSIL) and 20 healthy controls. Serum TOS and TAS were determined and OSI was calculated as the indicator of degree of oxidative stress. RESULTS: Serum TOS levels and OSI were highest in the HSIL group and there was a trend toward increasing serum TOS levels and OSI from ASCUS to HSIL group. CONCLUSION: The authors demonstrated that increased oxidative stress with altered antioxidant level is associated with abnormal cervical cytology. Serum oxidant and antioxidant status may provide guidance as a simple and cost-effective method for follow-up, treatment, and recommendation in all stages of lesions.

Mindfulness Meditation and Cognitive Behavioral Therapy Intervention Reduces Pain Severity and Sensitivity in Opioid-Treated Chronic Low Back Pain: Pilot Findings from a Randomized Controlled Trial.

OBJECTIVE: To assess benefits of mindfulness meditation and cognitive behavioral therapy (CBT)-based intervention for opioid-treated chronic low back pain (CLBP). DESIGN: 26-week parallel-arm pilot randomized controlled trial (Intervention and Usual Care versus Usual Care alone). SETTING: Outpatient. SUBJECTS: Adults with CLBP, prescribed ≥30 mg/day of morphine-equivalent dose (MED) for at least 3 months. METHODS: The intervention comprised eight weekly group sessions (meditation and CLBP-specific CBT components) and 30 minutes/day, 6 days/week of at-home practice. Outcome measures were collected at baseline, 8, and 26 weeks: primary-pain severity (Brief Pain Inventory) and function/disability (Oswestry Disability Index); secondary-pain acceptance, opioid dose, pain sensitivity to thermal stimuli, and serum pain-sensitive biomarkers (Interferon-γ; Tumor Necrosis Factor-α; Interleukins 1ß and 6; C-reactive Protein). RESULTS: Thirty-five (21 experimental, 14 control) participants were enrolled and completed the study. They were 51.8 ± 9.7 years old, 80% female, with severe CLBP-related disability (66.7 ± 11.4), moderate pain severity (5.8 ± 1.4), and taking 148.3 ± 129.2 mg/day of MED. Results of the intention-to-treat analysis showed that, compared with controls, the meditation-CBT group reduced pain severity ratings during the study (P = 0.045), with between-group difference in score change reaching 1 point at 26 weeks (95% Confidence Interval: 0.2,1.9; Cohen's d = 0.86), and decreased pain sensitivity to thermal stimuli (P < 0.05), without adverse events. Exploratory analyses suggested a relationship between the extent of meditation practice and the magnitude of intervention benefits. CONCLUSIONS: Meditation-CBT intervention reduced pain severity and sensitivity to experimental thermal pain stimuli in patients with opioid-treated CLBP.

The early pregnancy volume measurements in predicting pregnancy outcome.

OBJECTIVE: The authors' aim was to develop a logistic regression model based on the ultrasonographic parameters on maternities which are showing a healthy improvement process during the first trimester of pregnancy. MATERIAL AND METHODS: Using 2D transvaginal ultrasound imaging, the crown rump length (CRL), yolk sac (YS), and gestational sac (GS) diameters were recorded in 225 women with gestational age < 11 weeks. Simplified V = 0.523 x length x height x width formula was used for the volume calculations. The results which ended in abortion were not included in the study. RESULTS: Linear regression analyses between yolk sac volume (YSV), YSV = 0.026 + 0.0018 x CRL (r²: 0.15; p < 0.001), gestational sac volume (GSV), GSV= -9.6 + 1.7 x CRL (r²: 0.52; p < 0.001), and embryo volume (EV), EV = -1.64 + 0.18 x CRL (r²: 0.4; p < 0.001), and CRL was made and a linear relationship was detected. The volume measurements showed a meaningful correlation with the week of pregnancy. The space in the GS (GS volume-embryo volume) increased as the age of pregnancy became older (r² = 0.46; p < 0.001). DISCUSSION: The first volume value was made in the first trimester by transvaginal ultrasonography, which showed a correlation with the age of pregnancy.

QT interval changes in term pregnant women living at moderately high altitude.

OBJECTIVE: This study aimed to compare the QT interval changes in women with term pregnancy living at moderately high altitude (1890 m in Erzurum, Turkey) with those of women living at sea level (31 m in Istanbul, Turkey). MATERIALS AND METHODS: One-hundred ten women (n = 55, for each group) with full-term and single child pregnancies. Two different locations in that state were selected: Istanbul, Turkey, which is at 31 m above sea level (Group 1) and Erzurum, Turkey, at 1890 m above sea level (Group 2). Physicians from the two locations participated in the study. We estimated QTc, QTc Max, QTc Min, QT, and QTcd intervals. RESULTS: Moderately high altitude group had significantly longer QT parameters (QTc, QTc Max, QTc Min, QT, and QTcd intervals) compared with sea level group (P < 0.01, for all). CONCLUSIONS: According to our results, QT interval changes occur in term pregnant women living moderately high altitude. These changes may be associated with pregnancy-related cardiovascular complications in moderately high altitude.

Can we predict postpartum depression in pregnant women?

OBJECTIVE: The authors aimed to determine risk factors for postpartum depression (PPD) in this prospective study. MATERIALS AND METHODS: The study included 285 pregnant women. The first assessment was conducted during pregnancy and a second time at 24 weeks after delivery. The participants were asked to fill out a series of questionnaires, which included psychosocial variables and socio- demographic characteristics, the Beck Depression Inventory (BDI), and Edinburgh Postnatal Depression Scale (EPDS). After delivery, 276 mothers participated again in the study and filled out a similar series of questionnaires. RESULTS: A significant difference was not found between the socio-demographic and obstetric factors of mothers. A significant relation was found between the BDI score, which is used in antepartum depression evaluation, and EPDS score, which is used on postpartum depression evaluation (rho: 0.433 to 0.645, p < 0.0001). In cases in which BDI score was more than 6 were selected, phenomena in which could develop PPD had 90.3% sensitivity and 45.3% specificity. CONCLUSIONS: The authors found that there was a correlation between EPDS score and BDI. The rate of PPD was found to be significantly higher in women, who had a depression history. Patients who have a potential risk of PPD should be evaluated during the postpartum period in terms of depression.

Protein interaction profiling of the p97 adaptor UBXD1 points to a role for the complex in modulating ERGIC-53 trafficking.

UBXD1 is a member of the poorly understood subfamily of p97 adaptors that do not harbor a ubiquitin association domain or bind ubiquitin-modified proteins. Of clinical importance, p97 mutants found in familial neurodegenerative conditions Inclusion Body Myopathy Paget's disease of the bone and/or Frontotemporal Dementia and Amyotrophic Lateral Sclerosis are defective at interacting with UBXD1, indicating that functions regulated by a p97-UBXD1 complex are altered in these diseases. We have performed liquid chromatography-mass spectrometric analysis of UBXD1-interacting proteins to identify pathways in which UBXD1 functions. UBXD1 displays prominent association with ERGIC-53, a hexameric type I integral membrane protein that functions in protein trafficking. The UBXD1-ERGIC-53 interaction requires the N-terminal 10 residues of UBXD1 and the C-terminal cytoplasmic 12 amino acid tail of ERGIC-53. Use of p97 and E1 enzyme inhibitors indicate that complex formation between UBXD1 and ERGIC-53 requires the ATPase activity of p97, but not ubiquitin modification. We also performed SILAC-based quantitative proteomic profiling to identify ERGIC-53 interacting proteins. This analysis identified known (e.g. COPI subunits) and novel (Rab3GAP1/2 complex involved in the fusion of vesicles at the cell membrane) interactions that are also mediated through the C terminus of the protein. Immunoprecipitation and Western blotting analysis confirmed the proteomic interaction data and it also revealed that an UBXD1-Rab3GAP association requires the ERGIC-53 binding domain of UBXD1. Localization studies indicate that UBXD1 modules the sub-cellular trafficking of ERGIC-53, including promoting movement to the cell membrane. We propose that p97-UBXD1 modulates the trafficking of ERGIC-53-containing vesicles by controlling the interaction of transport factors with the cytoplasmic tail of ERGIC-53.

Physical Activity and Fatigue Symptoms: Neurotypical Adults and People with Chronic Multisymptom Illnesses.

For neurotypical adults, a single bout of low-to-moderate intensity physical activity usually transiently improves feelings of energy. Similar bouts of exercise have the opposite effect of increased feelings of fatigue when performed by samples with chronic multisymptom illnesses (CMIs) such as Long-COVID, Gulf War Illness (GWI), or Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). The short-term adoption of regular moderate intensity physical activity (typical experiments are 1 to 6 months) among neurotypical adults results in small-to-moderate improvements in self-reported feelings of fatigue, energy, and vitality. Small improvements in these feelings, or no change at all, occur for CMIs, but limited data precludes strong conclusions. The mechanisms of exercise effects on fatigue, whether acute or chronic, are poorly understood but likely involve multiple neural circuits and associated transmitters. For CMIs, the mechanisms of acute worsening of fatigue with exercise may be driven by the yet unknown pathophysiological mechanisms of the disease (perhaps involving brain, immune and autonomic system dysfunction, and their interactions). Likewise, fatigue improvements may depend on whether chronic physical activity is a disease-modifying treatment.

Exercise Training for Chronic Pain: Available Evidence, Current Recommendations, and Potential Mechanisms.

Chronic pain conditions pose a significant global burden of disability, with epidemiological data indicating a rising incidence. Exercise training is commonly recommended as a standalone or complementary approach for managing various chronic pain conditions like low back pain, osteoarthritis, rheumatoid arthritis, fibromyalgia syndrome, and neuropathic pain. Regardless of the specific condition or underlying cause (e.g., autoimmune disease, chronic inflammation), exercise training consistently leads to moderate to large reductions in pain. Moreover, exercise yields numerous benefits beyond pain alleviation, including small-to-moderate improvements in disability, quality of life, and physical function. Despite its efficacy, there is a lack of comprehensive research delineating the optimal intensity, duration, and type of exercise for maximal benefits; however, evidence suggests that sustained engagement in regular exercise or physical activity is necessary to achieve and maintain reductions in both clinical pain intensity ratings and the level that pain interferes with activities of daily living. Additionally, the precise mechanisms through which exercise mitigates pain remain poorly understood and likely vary based on the pathophysiological mechanisms underlying each condition.

Examination of Conditioned Pain Modulation in Myofascial TMD With Consideration of Temporal Summation.

Research on myofascial temporomandibular disorder (mTMD) has often focused on potential dysfunction in endogenous pain modulation. However, studies on the specific inhibitory and facilitatory components of endogenous pain modulation using conditioned pain modulation (CPM) and temporal summation of second pain (TSSP) have shown mixed results. This study aimed to 1) examine whether women with mTMD demonstrated efficient CPM compared to controls; 2) explore the association between independent measures of CPM and TSSP in women with mTMD relative to controls; and 3) determine whether resulting modulatory profiles differentially predicted pain intensity among cases. All participants were recruited from dental clinics. Cases were women who met the research diagnostic criteria for mTMD. Controls did not have facial pain on exam and were selected to be sociodemographically similar to cases. CPM and TSSP were assessed via independent psychophysical protocols. CPM was examined in linear mixed models predicting pain thresholds adjusted for age and stratified by TSSP. Mean CPM was estimated at a 2.2 (SD = 2.8) degree increase in pain thresholds (P ≤ .001), similar in cases and controls (P = .67). CPM was less efficient in cases with enhanced TSSP (P = .031), but not in controls. Although the double-pronociceptive profile of both low CPM and high TSSP trended higher among cases than controls, it did not predict higher levels of pain intensity among cases. This study does not support deficient inhibitory endogenous pain modulation in mTMD, but results suggest that inhibitory and facilitatory pain modulation should be examined concomitantly in the study of endogenous pain modulation. PERSPECTIVE: This manuscript presents a novel examination of inhibitory modulation by the level of facilitatory modulation in mTMD. The findings and approach may prove useful for mechanistic researchers studying endogenous pain modulation and clinical researchers seeking to jointly examine conditioned pain modulation and temporal summation in future research on chronic pain.