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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 -
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 -
Scientific Reports May 2024Androgen deprivation therapy (ADT) is the core treatment for advanced prostate cancer (PCa), with a proven survival benefit. ADT lowers circulating testosterone levels...
Androgen deprivation therapy (ADT) is the core treatment for advanced prostate cancer (PCa), with a proven survival benefit. ADT lowers circulating testosterone levels throughout the body, but with it comes a variety of reported side effects including fatigue, muscle wastage, weight gain, hot flushes and importantly cognitive impairment, depression, and mood swings. Testosterone has a key role in brain masculinization, but its direct effects are relatively poorly understood, due both to the brain's extreme complexity and the fact that some of testosterone activities are driven via local conversion to oestrogen, especially during embryonic development. The exact roles, function, and location of the androgen receptor (AR) in the adult male brain are still being discovered, and therefore the cognitive side effects of ADT may be unrecognized or under-reported. The age of onset of several neurological diseases overlap with PCa, therefore, there is a need to separate ADT side effects from such co-morbidities. Here we analysed the activity and expression level of the AR in the adult mouse brain, using an ARE-Luc reporter mouse and immunohistochemical staining for AR in all the key brain regions via coronal slices. We further analysed our data by comparing to the Allen Mouse Brain Atlas. AR-driven luciferase activity and distinct nuclear staining for AR were seen in several key brain areas including the thalamus, hypothalamus, olfactory bulb, cerebral cortex, Purkinje cells of the cerebellum and the hindbrain. We describe and discuss the potential role of AR in these areas, to inform and enable extrapolation to potential side effects of ADT in humans.
Topics: Receptors, Androgen; Animals; Mice; Brain; Male
PubMed: 38750183
DOI: 10.1038/s41598-024-61733-9 -
Frontiers in Neuroscience 2024Parkinson's disease (PD) is characterized by three main motor symptoms: bradykinesia, rigidity and tremor. PD is also associated with diverse non-motor symptoms that may...
Parkinson's disease (PD) is characterized by three main motor symptoms: bradykinesia, rigidity and tremor. PD is also associated with diverse non-motor symptoms that may develop in parallel or precede motor dysfunctions, ranging from autonomic system dysfunctions and impaired sensory perception to cognitive deficits and depression. Here, we examine the role of the progressive loss of dopaminergic transmission in behaviors related to the non-motor symptoms of PD in a mouse model of the disease (the TIF-IA strain). We found that in the period from 5 to 12 weeks after the induction of a gradual loss of dopaminergic neurons, mild motor symptoms became detectable, including changes in the distance between paws while standing as well as the swing speed and step sequence. Male mutant mice showed no apparent changes in olfactory acuity, no anhedonia-like behaviors, and normal learning in an instrumental task; however, a pronounced increase in the number of operant responses performed was noted. Similarly, female mice with progressive dopaminergic neuron degeneration showed normal learning in the probabilistic reversal learning task and no loss of sweet-taste preference, but again, a robustly higher number of choices were performed in the task. In both males and females, the higher number of instrumental responses did not affect the accuracy or the fraction of rewarded responses. Taken together, these data reveal discrete, dopamine-dependent non-motor symptoms that emerge in the early stages of dopaminergic neuron degeneration.
PubMed: 38745938
DOI: 10.3389/fnins.2024.1375265 -
Skin Research and Technology : Official... May 2024Many studies have indicated that negative emotions and personality traits are related to psoriasis, though few have provided causal evidence.
BACKGROUND
Many studies have indicated that negative emotions and personality traits are related to psoriasis, though few have provided causal evidence.
METHODS
Our analysis utilized 15 genome-wide association study datasets to identify instrumental variables associated with negative emotions, personality traits and psoriasis vulgaris. Two-sample Mendelian randomization was conducted to identify the causal associations of negative emotions and personality traits with psoriasis vulgaris. To mitigate bias from multiple tests, we adjusted p-values using the Benjamini-Hochberg method.
RESULTS
Our study revealed causal links between negative emotions and psoriasis vulgaris, including depressed affect, worry too long, feeling hurt, guilty feelings, mood swings, unenthusiasm, miserableness, fed-up feelings. However, there was no significant evidence of a causal relationship between feeling lonely and psoriasis vulgaris. Additionally, personality traits including neuroticism and openness to experience were found to have causal effects on psoriasis vulgaris. However, no significant evidence supported a causal relationship between agreeableness, conscientiousness, and extraversion with psoriasis vulgaris.
CONCLUSION
Our findings suggest that experiencing negative emotions including depressed affect, worrying excessively, feeling hurt, guilty feelings, mood swings, lack of enthusiasm, miserableness and fed-up feelings may pose risks for psoriasis vulgaris. Additionally, neuroticism is associated with a risk of psoriasis vulgaris. Conversely, the openness trait may serve a protective role against psoriasis vulgaris.
Topics: Humans; Psoriasis; Mendelian Randomization Analysis; Personality; Genome-Wide Association Study; Emotions; Polymorphism, Single Nucleotide
PubMed: 38743386
DOI: 10.1111/srt.13702 -
Clinical and Translational Allergy May 2024Asthma is the most common chronic disease among children and poses a significant threat to their health. This study aims to assess the relationship between various...
BACKGROUND
Asthma is the most common chronic disease among children and poses a significant threat to their health. This study aims to assess the relationship between various plasma proteins and childhood asthma, thereby identifying potential therapeutic targets.
METHODS
Based on publicly available genome-wide association study summary statistics, we employed a two-sample Mendelian randomization (MR) approach to elucidate the causal relationship between plasma proteins and asthma. Mediation analysis was then conducted to evaluate the indirect influence of plasma proteins on childhood asthma mediated through risk factors. Comprehensive analysis was also conducted to explore the association between plasma proteins and various phenotypes using the UK Biobank dataset.
RESULTS
MR analysis uncovered a causal relationship between 10 plasma proteins and childhood asthma. Elevated levels of seven proteins (TLR4, UBP25, CBR1, Rac GTPase-activating protein 1 [RGAP1], IL-21, MICB, and PDE4D) and decreased levels of three proteins (GSTO1, LIRB4 and PIGF) were associated with an increased risk of childhood asthma. Our findings further validated the connections between reported risk factors (body mass index, mood swings, hay fever or allergic rhinitis, and eczema or dermatitis) and childhood asthma. Mediation analysis revealed the influence of proteins on childhood asthma outcomes through risk factors. Furthermore, the MR analysis identified 73 plasma proteins that exhibited causal associations with at least one risk factor for childhood asthma. Among them, RGAP1 mediates a significant proportion (25.10%) of the risk of childhood asthma through eczema or dermatitis. Finally, a phenotype-wide association study based on these 10 proteins and 1403 diseases provided novel associations between these biomarkers and multiple phenotypes.
CONCLUSION
Our study comprehensively investigated the causal relationship between plasma proteins and childhood asthma, providing novel insights into potential therapeutic targets.
PubMed: 38730525
DOI: 10.1002/clt2.12357 -
PloS One 2024Previous cross-sectional studies have identified multiple potential risk factors for functional dyspepsia (FD). However, the causal associations between these factors...
BACKGROUND
Previous cross-sectional studies have identified multiple potential risk factors for functional dyspepsia (FD). However, the causal associations between these factors and FD remain elusive. Here we aimed to fully examine the causal relationships between these factors and FD utilizing a two-sample MR framework.
METHODS
A total of 53 potential FD-related modifiable factors, including those associated with hormones, metabolism, disease, medication, sociology, psychology, lifestyle and others were obtained through a comprehensive literature review. Independent genetic variants closely linked to these factors were screened as instrumental variables from genome-wide association studies (GWASs). A total of 8875 FD cases and 320387 controls were available for the analysis. The inverse variance weighted (IVW) method was employed as the primary analytical approach to assess the relationship between genetic variants of risk factors and the FD risk. Sensitivity analyses were performed to evaluate the consistency of the findings using the weighted median model, MR-Egger and MR-PRESSO methods.
RESULTS
Genetically predicted depression (OR 1.515, 95% confidence interval (CI) 1.231 to 1.865, p = 0.000088), gastroesophageal reflux disease (OR 1.320, 95%CI 1.153 to 1.511, p = 0.000057) and years of education (OR 0.926, 95%CI 0.894 to 0.958, p = 0.00001) were associated with risk for FD in univariate MR analyses. Multiple medications, alcohol consumption, poultry intake, bipolar disorder, mood swings, type 1 diabetes, elevated systolic blood pressure and lower overall health rating showed to be suggestive risk factors for FD (all p<0.05 while ≥0.00167). The positive causal relationship between depression, years of education and FD was still significant in multivariate MR analyses.
CONCLUSIONS
Our comprehensive MR study demonstrated that depression and lower educational attainment were causal factors for FD at the genetic level.
Topics: Humans; Dyspepsia; Risk Factors; Mendelian Randomization Analysis; Genome-Wide Association Study; Depression; Gastroesophageal Reflux; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease
PubMed: 38718064
DOI: 10.1371/journal.pone.0302809