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Life (Basel, Switzerland) Jun 2024Menopausal women experience changes in ovarian activity and fluctuating hormone levels. The aim of this study was to detect ongoing sleep and nutritional problems in...
Menopausal women experience changes in ovarian activity and fluctuating hormone levels. The aim of this study was to detect ongoing sleep and nutritional problems in postmenopausal women. This study was conducted with 62 postmenopausal women who had been diagnosed with major depressive disorder, were aged 42-64, were not dieting for at least 1 month, and had been using antidepressants for at least 6 months. The Pittsburgh Sleep Quality Index and Depression Anxiety Stress Scale-42 were used. Anthropometric measurements were taken and body composition analysis was performed. The prevalence of obesity and overweight were 12.9% and 71%, respectively. Hot flashes, night sweats, and mood swing were more common in those who had been through menopause for <5 years. Also, the PSQI, Depression, and Stress scores of those women were higher. Women who had been menopausal for ≥5 years had a higher BMI, waist/hip ratio, and fat mass and better sleep quality and lower daytime dysfunction according to the PSQI. Energy and fat intake were higher, while protein, vitamin C, and calcium intakes were lower in women who had been menopausal for ≥5 years. It is crucial for healthcare professionals to review approaches for early and late menopausal periods and to individualize treatment options, especially in patients whose symptoms persist.
PubMed: 38929757
DOI: 10.3390/life14060775 -
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 -
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 -
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 -
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 -
BMJ Open Sport & Exercise Medicine 2024People with Parkinson's disease (PD) face disruptions in arm swing (AS) motion during walking, including a reduction in amplitude and an increase in asymmetry. Both...
People with Parkinson's disease (PD) face disruptions in arm swing (AS) motion during walking, including a reduction in amplitude and an increase in asymmetry. Both conditions are detrimental to gait performance. Nordic walking (NW) is a walking modality that uses poles and can positively affect the parameters of AS. This study aims to compare an NW with a free walking (FW) protocol and investigate its effects on AS asymmetry, AS amplitude and gait parameters in people with PD. Twenty-eight people with PD, stages 1-3 on the Hoehn and Yahr Scale, will be randomly assigned to the NW training group (n=14) or the FW training group (n=14). The primary outcomes are amplitude asymmetry of AS (%) and AS amplitude (deg). We will also analyse temporospatial measurements during walking, functional mobility and quality of life. Blinded researchers will conduct evaluations at baseline (T0), postintervention (T1) and at 1 month follow-up (T2). Participants will complete 24 supervised NW or FW training sessions for 12 weeks. This is the first study to address the effects of NW on the asymmetry of AS, AS amplitude and its influence on gait parameters. We hypothesise that an NW programme in PD will reduce the asymmetry and increase the AS amplitude during gait to a greater extent than FW. The results of this study may provide new evidence to understand the effects of NW on gait in people with PD. The study was registered in ClinicalTrial.gov (NCT06342271).
PubMed: 38808265
DOI: 10.1136/bmjsem-2024-002029 -
PloS One 2024Women living in high-quality healthcare systems are more likely to use oral contraceptives at some point in their lives. Research findings have sparked controversial...
BACKGROUND
Women living in high-quality healthcare systems are more likely to use oral contraceptives at some point in their lives. Research findings have sparked controversial discussions about contraception in the scientific community and the media, potentially leading to higher rates of method discontinuation. Understanding the underlying motives for method discontinuation is crucial for reproductive health equity and future programming interventions. To address this question, this study aims to explore women's experiences of oral contraceptive use and discontinuation on YouTube.
METHODS
A concurrent explanatory mixed-methods design was used to conduct content analysis of German YouTube videos. The information from 175 videos of 158 individuals was extracted through quantitative descriptive content analysis. Twenty-one individuals were included in the qualitative content analysis.
FINDINGS
The body was a recurring theme in the pill biographies. Women described, for example, bodily sensations as reasons for taking and stopping the pill. They also described positive and negative side effects while taking the pill and after stopping. The most common side effects of taking the pill mentioned by YouTubers were mood swings (76/158), weight gain (45/158), headaches (33/158), and depressed mood (45/158). The symptoms after discontinuation reported most were facial skin impurities (108/158), decreased mood swings (47/158), hair loss (42/158), and weight loss (36/158). Overall, women overwhelmingly rated their discontinuation experience as positive (87/91).
CONCLUSIONS
The study identified key symptoms of oral contraceptive initiation and discontinuation by portraying the experiences of female YouTubers, adding valuable insights to the understanding of method initiation and discontinuation. Further research is needed to explore women's personal experiences with method discontinuation beyond the YouTube platform.
Topics: Humans; Female; Contraceptives, Oral; Adult; Social Media; Young Adult; Video Recording; Adolescent; Contraception Behavior; Middle Aged
PubMed: 38787833
DOI: 10.1371/journal.pone.0302316 -
Cureus Apr 2024Background Postpartum depression (PPD) is a significant public health concern globally characterized by a spectrum of mood disturbances ranging from mild mood swings to...
Background Postpartum depression (PPD) is a significant public health concern globally characterized by a spectrum of mood disturbances ranging from mild mood swings to severe depressive episodes initiating within four weeks post childbirth and potentially persisting up to 12 months. Besides affecting the mother, it also affects the mental health and development of the babies born to affected mothers. Despite its considerable burden and potential adverse effects on both maternal and child well-being, PPD often goes undetected and untreated. Materials and methods A cross-sectional study was conducted from January 2024 to March 2024 at a tertiary care center in Gorakhpur to assess PPD in 280 postpartum women. The Edinburgh Postnatal Depression Scale (EPDS) score ≥ 10 was used to confirm depression. Data collection involved a pretested, structured questionnaire. Data were analyzed using SPSS version 22 (IBM Corp., Armonk, NY). A p-value < 0.05 was considered statistically significant. Results The prevalence of PPD was 12.14%. Age and education were significant sociodemographic risk factors (p < 0.05). In psychosocial factors, adverse life events (p < 0.001), wishing for a male child but giving birth to a female (p = 0.01), domestic violence (p = 0.005), relationship issues, an alcoholic spouse (p = 0.01), and poor in-law relations (p < 0.001) were found to be linked to PPD. Obstetric factors such as complicated antenatal history, physical illness, cesarean section, complicated intranatal history, and postpartum complications were also found to be important factors. Conclusion PPD affects many women, emphasizing the need for effective measures. Initiatives like the appointment of healthcare counselors and PPD screening programs in healthcare settings are essential to detect and support affected mothers.
PubMed: 38770470
DOI: 10.7759/cureus.58653