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Quality of Life Research : An... Jun 2024This study aimed to produce a patient-centered understanding of mental health symptoms of people with the post-COVID-19 syndrome (PCS).
OBJECTIVES
This study aimed to produce a patient-centered understanding of mental health symptoms of people with the post-COVID-19 syndrome (PCS).
METHODS
A cross-sectional analysis of 414 participants in a longitudinal study was carried out involving people who self-identified as having symptoms of PCS. People were asked to name their most frequent and most bothersome mental health symptoms affected by PCS using the structure of the Patient Generated Index (PGI). The text threads from the PGI were grouped into topics using BERTopic analysis.
RESULTS
20 topics were identified from 818 text threads referring to PCS mental health symptoms. 35% of threads were identified as relating to anxiety, discussed in terms of five topics: generalized/social anxiety, fear/worry, post-traumatic stress, panic, and nervous. 29% of threads were identified as relating to low mood, represented by five topics: depression, discouragement, emotional distress, sadness, and loneliness. A cognitive domain (22% of threads) was covered by four topics referring to concentration, memory, brain fog, and mental fatigue. Topics related to frustration, anger, irritability. and mood swings (7%) were considered as one domain and there were separate topics related to motivation, insomnia, and isolation.
CONCLUSIONS
This novel method of digital transformation of unstructured text data uncovered different ways in which people think about classical mental health domains. This information could be used to evaluate whether existing measures cover the content identified by people with PCS, to initiate a clinical conversation, or to justify the development of a new measure of the mental health impact of PCS.
PubMed: 38916660
DOI: 10.1007/s11136-024-03719-8 -
ELife Jun 2024Allosteric cooperativity between ATP and substrates is a prominent characteristic of the cAMP-dependent catalytic subunit of protein kinase A (PKA-C). This long-range...
Allosteric cooperativity between ATP and substrates is a prominent characteristic of the cAMP-dependent catalytic subunit of protein kinase A (PKA-C). This long-range synergistic action is involved in substrate recognition and fidelity, and it may also regulate PKA's association with regulatory subunits and other binding partners. To date, a complete understanding of this intramolecular mechanism is still lacking. Here, we integrated NMR(Nuclear Magnetic Resonance)-restrained molecular dynamics simulations and a Markov State Model to characterize the free energy landscape and conformational transitions of PKA-C. We found that the apoenzyme populates a broad free energy basin featuring a conformational ensemble of the active state of PKA-C (ground state) and other basins with lower populations (excited states). The first excited state corresponds to a previously characterized inactive state of PKA-C with the αC helix swinging outward. The second excited state displays a disrupted hydrophobic packing around the regulatory (R) spine, with a flipped configuration of the F100 and F102 residues at the αC-β4 loop. We validated the second excited state by analyzing the F100A mutant of PKA-C, assessing its structural response to ATP and substrate binding. While PKA-C preserves its catalytic efficiency with Kemptide, this mutation rearranges the αC-β4 loop conformation, interrupting the coupling of the two lobes and abolishing the allosteric binding cooperativity. The highly conserved αC-β4 loop emerges as a pivotal element to control the synergistic binding of nucleotide and substrate, explaining how mutations or insertions near or within this motif affect the function and drug sensitivity in homologous kinases.
Topics: Molecular Dynamics Simulation; Allosteric Regulation; Adenosine Triphosphate; Catalytic Domain; Cyclic AMP-Dependent Protein Kinases; Protein Conformation; Protein Binding; Nucleotides; Substrate Specificity; Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
PubMed: 38913408
DOI: 10.7554/eLife.91506 -
The European Journal of Contraception &... Jun 2024To describe the effects of estetrol (E4) 15 mgdrospirenone (DRSP) 3 mg on physical and emotional premenstrual and menstrual symptoms.
PURPOSE
To describe the effects of estetrol (E4) 15 mgdrospirenone (DRSP) 3 mg on physical and emotional premenstrual and menstrual symptoms.
MATERIALS AND METHODS
We used Menstrual Distress Questionnaire (MDQ) data from a phase-3 trial (NCT02817828) in Europe and Russia with participants (18 - 50 years) using E4/DRSP for up to 13 cycles. We assessed mean changes in MDQ--scores from baseline to end of treatment in premenstrual (4 days before most recent flow) and menstrual (most recent flow) scores for 4 MDQ domains in starters and switchers (use of hormonal contraception in prior 3 months) and performed a shift analysis on individual symptoms within each domain.
RESULTS
Of 1,553 treated participants, 1,398(90.0%), including 531(38%) starters, completed both MDQs. Starters reported improvements for premenstrual Pain (-1.4), Water Retention (-3.3) and Negative Affect (-2.5); and for menstrual Pain (-3.5), Water Retention (-3.4), and Negative Affect (-2.7) (all < 0.01). For switchers, no changes were significant except an increase in premenstrual (+1.0, = 0.02) and menstrual (+1.5, = 0.003) Water Retention. We observed a change in symptom intensity in >40% of participants for Cramps, Backache and Fatigue (domain Pain), Painful or Tender Breast and Swelling (domain Water Retention) and Mood Swings and Irritability (domain Negative Affect).
CONCLUSION
E4/DRSP starters experienced significant improvements in the domains Pain, Water Retention and Negative Affect particularly benefiting those with more severe baseline symptoms. Switchers showed minimal changes.
PubMed: 38904165
DOI: 10.1080/13625187.2024.2359117 -
Child and Adolescent Psychiatry and... Jun 2024Children with affective dysregulation (AD) show an excessive reactivity to emotionally positive or negative stimuli, typically manifesting in chronic irritability,...
BACKGROUND
Children with affective dysregulation (AD) show an excessive reactivity to emotionally positive or negative stimuli, typically manifesting in chronic irritability, severe temper tantrums, and sudden mood swings. AD shows a large overlap with externalizing and internalizing disorders. Given its transdiagnostic nature, AD cannot be reliably and validly captured only by diagnostic categories such as disruptive mood dysregulation disorder (DMDD). Therefore, this study aimed to evaluate two semi-structured clinical interviews-one for parents and one for children.
METHODS
Both interviews were developed based on existing measures that capture particular aspects of AD. We analyzed internal consistencies and interrater agreement to evaluate their reliability. Furthermore, we analyzed factor loadings in an exploratory factor analysis, differences in interview scores between children with and without co-occurring internalizing and externalizing disorders, and associations with other measures of AD and of AD-related constructs. The evaluation was performed in a screened community sample of children aged 8-12 years (n = 445). Interrater reliability was additionally analyzed in an outpatient sample of children aged 8-12 years (n = 27).
RESULTS
Overall, internal consistency was acceptable to good. In both samples, we found moderate to excellent interrater reliability on a dimensional level. Interrater agreement for the dichotomous diagnosis DMDD was substantial to perfect. In the exploratory factor analysis, almost all factor loadings were acceptable. Children with a diagnosis of disruptive disorder, attention-deficit/hyperactivity disorder, or any disorder (disruptive disorder, attention-deficit/hyperactivity disorder, and depressive disorder) showed higher scores on the DADYS interviews than children without these disorders. The correlation analyses revealed the strongest associations with other measures of AD and measures of AD-specific functional impairment. Moreover, we found moderate to very large associations with internalizing and externalizing symptoms and moderate to large associations with emotion regulation strategies and health-related quality of life.
CONCLUSIONS
The analyses of internal consistency and interrater agreement support the reliability of both clinical interviews. Furthermore, exploratory factor analysis, discriminant analyses, and correlation analyses support the interviews' factorial, discriminant, concurrent, convergent, and divergent validity. The interviews might thus contribute to the reliable and valid identification of children with AD and the assessment of treatment responses.
TRIAL REGISTRATION
ADOPT Online: German Clinical Trials Register (DRKS) DRKS00014963. Registered 27 June 2018.
PubMed: 38902809
DOI: 10.1186/s13034-024-00762-8 -
Animals : An Open Access Journal From... May 2024Osteoarthritis is a common degenerative disease in dogs, often manifested as pain, joint swelling, and lameness. Despite the lack of scientific evidence for its...
Osteoarthritis is a common degenerative disease in dogs, often manifested as pain, joint swelling, and lameness. Despite the lack of scientific evidence for its treatment efficacy, transcutaneous electrical nerve stimulation (TENS) is used in dogs as a pain-relieving treatment. This randomised single-blinded cross-over study investigated the effect of TENS on gait parameters in fifteen dogs with osteoarthritis. Stance time, swing time, stride time, stride length, peak vertical force (%BW), vertical impulse (%BW*sec), and symmetry indices were obtained using a pressure-sensitive mat. TENS treatment of 80 Hz and 100 µs with an individually selected amplitude was conducted for 45 min once daily for a treatment period of seven or ten days. No significant differences were seen between TENS and placebo for any of the gait parameters. Hence, in this study, TENS did not affect gait parameters, compared to placebo. Further studies are needed to confirm the observations.
PubMed: 38891673
DOI: 10.3390/ani14111626 -
BMC Women's Health Jun 2024Observational data indicates a connection between emotional discomfort, such as anxiety and depression, and uterine fibroids (UFs). However, additional investigation is...
BACKGROUND
Observational data indicates a connection between emotional discomfort, such as anxiety and depression, and uterine fibroids (UFs). However, additional investigation is required to establish the causal relationship between them. Hence, we assessed the reciprocal causality between four psychological disorders and UFs utilizing two-sample Mendelian randomization (MR).
METHODS
To evaluate the causal relationship between four types of psychological distress (depressive symptoms, severe depression, anxiety or panic attacks, mood swings) and UFs, bidirectional two-sample MR was employed, utilizing single nucleotide polymorphisms (SNPs) associated with these conditions. Both univariate MR (UVMR) and multivariate MR (MVMR) primarily applied inverse variance weighted (IVW) as the method for estimating potential causal effects. Complementary approaches such as MR Egger, weighted median, simple mode, and weighted mode were utilized to validate the findings. To assess the robustness of our MR results, we conducted sensitivity analyses using Cochran's Q-test and the MR Egger intercept test.
RESULTS
The results of our UVMR analysis suggest that genetic predispositions to depressive symptoms (Odds Ratio [OR] = 1.563, 95% Confidence Interval [CI] = 1.209-2.021, P = 0.001) and major depressive disorder (MDD) (OR = 1.176, 95% CI = 1.044-1.324, P = 0.007) are associated with an increased risk of UFs. Moreover, the IVW model showed a nominally significant positive correlation between mood swings (OR: 1.578; 95% CI: 1.062-2.345; P = 0.024) and UFs risk. However, our analysis did not establish a causal relationship between UFs and the four types of psychological distress. Even after adjusting for confounders like body mass index (BMI), smoking, alcohol consumption, and number of live births in the MVMR, the causal link between MDD and UFs remained significant (OR = 1.217, 95% CI = 1.039-1.425, P = 0.015).
CONCLUSIONS
Our study presents evidence supporting the causal relationship between genetic susceptibility to MDD and the incidence of UFs. These findings highlight the significance of addressing psychological health issues, particularly depression, in both the prevention and treatment of UFs.
Topics: Humans; Mendelian Randomization Analysis; Female; Leiomyoma; Polymorphism, Single Nucleotide; Depression; Psychological Distress; Genetic Predisposition to Disease; Anxiety; Uterine Neoplasms; Causality; Panic Disorder
PubMed: 38890689
DOI: 10.1186/s12905-024-03196-8 -
Journal of Sports Sciences May 2024Research assessing the effects of mouthpieces on an individual's aerobic, anaerobic, or muscular performance have attributed cited improvements to the participant's...
Research assessing the effects of mouthpieces on an individual's aerobic, anaerobic, or muscular performance have attributed cited improvements to the participant's ability to jaw clench. Jaw clenching research finds positive outcomes with the task of jaw clenching with targeted muscle groups in a controlled laboratory setting. Thus, the study's goal was to determine if the addition of a mouthpiece would positively affect performance outcomes in a field-based whole-body muscle movement. Fourteen participants (8=F and 6=M) NCAA softball and baseball athletes completed 5 maximal bat swings with and without a mouthpiece in 4 conditions: no jaw clenching (NC), mouthpiece and jaw clenching (MP+C), mouthpiece only (MP), and jaw clenching only (C). Significant differences occurred in conditions, with the highest velocity noted in the combined condition of MP+C (71.9 mph) as compared to NC (67.9 mph), MP (68.6 mph), and C (70.9 mph). A repeated measures ANOVA demonstrated significant differences with bat swing velocity (F = 13.19, df 3, < 0.0001). Pairwise comparisons revealed significant differences in MP+C with MP ( = 0.007); MP+C with NC ( = 0.001), and C with NC ( = 0.009). The results of this study provide evidence of jaw clenching's positive effects on the dynamic, whole-body explosive activity of a bat swing.
Topics: Humans; Male; Baseball; Young Adult; Female; Athletic Performance; Jaw; Mouth Protectors; Biomechanical Phenomena; Movement; Chiroptera; Adult; Sports Equipment
PubMed: 38873943
DOI: 10.1080/02640414.2024.2363714 -
Optics Express Jun 2024The Line Height Absorption (LHA) method uses absorption of light to estimate chlorophyll-a. While most users consider regional variability and apply corrections, the...
The Line Height Absorption (LHA) method uses absorption of light to estimate chlorophyll-a. While most users consider regional variability and apply corrections, the effect of temporal variability is typically not explored. The Northern Gulf of Alaska (NGA) was selected for this study because there was no published regional value and its large swings in temporal productivity would make it a good candidate to evaluate the effect of temporal variability on the relationship. The mean NGA value of 0.0114 obtained here should be treated with caution, as variation in the slope of the relationship (a*), and thus chlorophyll-a estimates, in the NGA region varied by ∼25% between spring (a* = 0.0109) and summer (a* = 0.0137). Results suggest that this change is driven by a shift in pigment packaging and cell size associated with changes in mixed layer depth and stratification. Consideration of how temporal variability may affect the accuracy of the LHA method in other regions is thus recommended.
PubMed: 38859430
DOI: 10.1364/OE.521758 -
Human Movement Science Jun 2024Parkinson's disease (PD) causes gait abnormalities that may be associated with an arm swing reduction. Medication and freezing of gait (FoG) may influence gait...
INTRODUCTION
Parkinson's disease (PD) causes gait abnormalities that may be associated with an arm swing reduction. Medication and freezing of gait (FoG) may influence gait characteristics. However, these comparisons do not consider differences in gait speed and clinical characteristics in individuals with PD.
OBJECTIVE
This study aims to analyze the effect of FoG and medication on the biomechanics of the trunk and upper limbs during gait in PD, controlling for gait speed and clinical differences between groups.
METHODS
Twenty-two people with a clinical diagnosis of idiopathic PD in ON and OFF medication (11 FoG), and 35 healthy participants (control) were selected from two open data sets. All participants walked on the floor on a 10-m-long walkway. The joint and linear kinematic variables of gait were compared: (1) Freezers and nonfreezers in the ON condition and control; (2) Freezers and nonfreezers in the OFF condition and control; (3) Group (freezers and nonfreezers) and medication.
RESULTS
The disease affects the upper limbs more strongly but not the trunk. The medication does not significantly influence the joint characteristics but rather the linear wrist displacement. The FoG does not affect trunk movement and partially influences the upper limbs. The interaction between medications and FoG suggests that the medication causes more substantial improvement in freezers than in nonfreezers.
CONCLUSION
The study shows differences in the biomechanics of the upper limbs of people with PD, FoG, and the absence of medication. The future rehabilitation protocol should consider this aspect.
PubMed: 38850765
DOI: 10.1016/j.humov.2024.103242 -
Therapeutic Advances in... 2024This case report examines the possible correlation between the clozapine/norclozapine ratio and the occurrence of constipation and paralytic ileus. We present the case...
This case report examines the possible correlation between the clozapine/norclozapine ratio and the occurrence of constipation and paralytic ileus. We present the case of a 42-year-old patient diagnosed with schizoaffective disorder undergoing clozapine therapy. Despite intensive treatment with clozapine, haloperidol, valproic acid and biweekly electroconvulsive therapy sessions for over a year, florid psychotic symptoms and fluctuating mood swings persisted. Therefore, valproic acid was replaced by carbamazepine, a potent inducer of several CYP450-enzymes. To maintain clozapine plasma levels, fluvoxamine, a CYP1A2-inhibitor, was introduced at a dose of 25 mg before this switch. After addition of carbamazepine, there was a significant decline in clozapine levels, necessitating an increase in fluvoxamine dosage to 50 mg. Five weeks later the patient was admitted to a general hospital with a diagnosis of paralytic ileus. Treatment with enemas proved effective. Drug concentration analysis revealed a 2.5-fold increase in norclozapine levels in the weeks preceding hospital admission, resulting in an inverted clozapine/norclozapine ratio. Treatment with clozapine, carbamazepine and fluvoxamine was continued as the patient demonstrated clinical improvement on carbamazepine. Concurrently, an intensive laxative regimen was initiated. Two weeks later, the patient was readmitted to the general hospital due to suspected paralytic ileus and faecal vomiting, once again displaying an inverted clozapine/norclozapine ratio. We discuss potential mechanisms contributing to the occurrence of the paralytic ileus in this patient, including the antagonism of muscarinic M3 receptors by both clozapine and norclozapine, as well as the agonism of delta-opioid receptors by norclozapine. This case highlights the potential significance of both the clozapine/norclozapine ratio and absolute norclozapine levels as risk factors for constipation and paralytic ileus in patients on clozapine therapy.
PubMed: 38827014
DOI: 10.1177/20451253241255487