Innovative Approach for Depression Treatment: Two Ways of Modifying the Gut-Microbiome to Treat Major Depressive Disorder

Depression is a debilitating disorder that affects people worldwide. However, at least one third of patients do not respond to existing therapies, and novel treatment methods are necessary. A promising new approach for treating depression targets the microbiota-gut-brain axis, which is linked to physiological, behavioral, and cognitive functions affected in major depressive disorder. Probiotics and fecal microbiota transplantation are two possible ways to modify the microbiota-gut-brain axis. The first study in this thesis (Doll et al., 2022) presents two patients with diagnosed depression treated with fecal microbiota transplantation as an add-on therapy. Depressive symptoms decreased for both patients four weeks after the transplantation, with the effects lasting up to eight weeks in one patient. Gastrointestinal symptoms were reflected in microbiota changes and improved in one patient. In the second study (Schaub et al., 2022), we examined the effect of a probiotic supplementation on depressive symptoms, the gut microbiota, and the brain in a randomized controlled trial. Depressive symptoms decreased over time in both groups, but the decrease was stronger in the probiotic group. Probiotics increased the abundance of the genus Lactobacillus, which was associated with decreased depressive symptoms in the probiotics group. Finally, putamen activation in response to neutral faces was significantly decreased after the probiotic intervention. In the third study (Schneider et al., submitted), we investigated the effect of the probiotic supplementation on cognitive functions, brain-derived neurotrophic factor, and the brain. We found a significantly improved immediate recall for the probiotics group immediately after intervention and a trend for a time-group-interaction considering all timepoints. We also found a time-group-interaction in hippocampus activation during working memory processing, revealing a remediated hippocampus function in the probiotic group. However, we did not find significant changes of brain-derived neurotrophic factor. The results of the three studies highlight the role of the microbiota-gut-brain axis in depression and emphasize the potential of adjuvant microbiota-related treatment approaches as accessible, pragmatic, and non-stigmatizing therapies for depression. Nonetheless, the safety issues of fecal microbiota transplantation and the modest sample size of our studies imply that large-scale studies are needed to better understand the underlying mechanisms of depression and the microbiota-gut-brain axis and to replicate and validate our results

Ultrathin, Oil-Compatible, Lubricious Polymer Coatings: A Comparison of Grafting-To and Grafting-From Strategies

A grafting-to approach is described as a means of fabricating ultrathin, oil-compatible, friction-reducing coatings. The tribological properties of grafted-to coatings of poly(dodecyl methacrylate) (P12MA), prepared by means of a photoactivated perfluorophenylazide adhesion promoter, were compared with those of grafted-from coatings of the same polymer of comparable molecular weight, prepared via surface-initiated, atom-transfer radical polymerisation. It was shown that in a sub-hydrodynamic regime (i.e. boundary/brush lubrication), both coating types can be equivalently effective, exhibiting very low friction coefficients (0.02) against a bare silica countersurface with no detectable wear over the duration of the test (around 1,000 cycles, and maximal Hertzian contact pressure ca 170MPa as calculated for a bare-bare configuration), providing that sufficiently viscous base lubricants are employe

AUTO-ORGANIZAÇÃO E OS IDOSOS: A INTERLOCUÇÃO NECESSÁRIA ATRAVÉS DE UM FÓRUM

O presente artigo apresenta como o recurso fórum pôde propiciar um processo de aprendizagem a luz da teoria da auto-organização. Para tanto, foi utilizado na coleta de dados o AVA ROODA em um curso para idosos desenvolvido na UFRGS.Por meio da análise de 21 postagens realizadas por 16 idosos ao longo do curso constatou-se que o processo de escrita de narrativas levou à reflexão, mudança de comportamento e adoção de atitudes que contemplam a qualidade de vida, ou em outraspalavras, ao processo de envelhecimento ativo

Randomised controlled trial of physiotherapy compared with advice for low back pain

Objective To measure the effectiveness of routine physiotherapy compared with an assessment session and advice from a physiotherapist for patients with low back pain.Design Pragmatic, multicentre, randomised controlled trial.Setting Seven British NHS physiotherapy departments.Participants 286 patients with low back pain of more than six weeks' duration.Intervention Routine physiotherapy or advice on remaining active from a physiotherapist. Both groups received an advice book.Main outcome measures Primary outcome was scores on the Oswestry disability index at 12 months. Secondary outcomes were scores on the Oswestry disability index (two and six months), scores on the Roland and Morris disability questionnaire and SF-36 (2, 6 and 12 months), and patient perceived benefit from treatment (2, 6, and 12 months).Results 200 of 286 patients (70%) provided follow up information at 12 months. Patients in the therapy group reported enhanced perceptions of benefit, but there was no evidence of a long term effect of physiotherapy in either disease specific or generic outcome measures (mean difference in change in Oswestry disability index scores at 12 months −1.0%, 95% confidence interval −3.7% to 1.6%). The most common treatments were low velocity spinal joint mobilisation techniques (72%, 104 of 144 patients) and lumbar spine mobility and abdominal strengthening exercises (94%, 136 patients).Conclusions Routine physiotherapy seemed to be no more effective than one session of assessment and advice from a physiotherapist

The comorbidity profiles and medication issues of patients with multiple system atrophy:a systematic cross-sectional analysis

BACKGROUND: Multiple system atrophy (MSA) is a complex and fatal neurodegenerative movement disorder. Understanding the comorbidities and drug therapy is crucial for MSA patients' safety and management.OBJECTIVES: To investigate the pattern of comorbidities and aspects of drug therapy in MSA patients.METHODS: Cross-sectional data of MSA patients according to Gilman et al. (2008) diagnostic criteria and control patients without neurodegenerative diseases (non-ND) were collected from German, multicenter cohorts. The prevalence of comorbidities according to WHO ICD-10 classification and drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were identified using AiDKlinik®.RESULTS: The analysis included 254 MSA and 363 age- and sex-matched non-ND control patients. MSA patients exhibited a significantly higher burden of comorbidities, in particular diseases of the genitourinary system. Also, more medications were prescribed MSA patients, resulting in a higher prevalence of polypharmacy. Importantly, the risk of potential drug-drug interactions, including severe interactions and contraindicated combinations, was elevated in MSA patients. When comparing MSA-P and MSA-C subtypes, MSA-P patients suffered more frequently from diseases of the genitourinary system and diseases of the musculoskeletal system and connective tissue.CONCLUSIONS: MSA patients face a substantial burden of comorbidities, notably in the genitourinary system. This, coupled with increased polypharmacy and potential drug interactions, highlights the complexity of managing MSA patients. Clinicians should carefully consider these factors when devising treatment strategies for MSA patients.</p

Leisure Time Physical Activity of Moderate to Vigorous Intensity and Mortality: A Large Pooled Cohort Analysis

Background: Leisure time physical activity reduces the risk of premature mortality, but the years of life expectancy gained at different levels remains unclear. Our objective was to determine the years of life gained after age 40 associated with various levels of physical activity, both overall and according to body mass index (BMI) groups, in a large pooled analysis. Methods and Findings: We examined the association of leisure time physical activity with mortality during follow-up in pooled data from six prospective cohort studies in the National Cancer Institute Cohort Consortium, comprising 654,827 individuals, 21–90 y of age. Physical activity was categorized by metabolic equivalent hours per week (MET-h/wk). Life expectancies and years of life gained/lost were calculated using direct adjusted survival curves (for participants 40+ years of age), with 95% confidence intervals (CIs) derived by bootstrap. The study includes a median 10 y of follow-up and 82,465 deaths. A physical activity level of 0.1–3.74 MET-h/wk, equivalent to brisk walking for up to 75 min/wk, was associated with a gain of 1.8 (95% CI: 1.6–2.0) y in life expectancy relative to no leisure time activity (0 MET-h/wk). Higher levels of physical activity were associated with greater gains in life expectancy, with a gain of 4.5 (95% CI: 4.3–4.7) y at the highest level (22.5+ MET-h/wk, equivalent to brisk walking for 450+ min/wk). Substantial gains were also observed in each BMI group. In joint analyses, being active (7.5+ MET-h/wk) and normal weight (BMI 18.5–24.9) was associated with a gain of 7.2 (95% CI: 6.5–7.9) y of life compared to being inactive (0 MET-h/wk) and obese (BMI 35.0+). A limitation was that physical activity and BMI were ascertained by self report. Conclusions: More leisure time physical activity was associated with longer life expectancy across a range of activity levels and BMI groups

The comorbidity and co-medication profile of patients with progressive supranuclear palsy

BackgroundProgressive supranuclear palsy (PSP) is usually diagnosed in elderly. Currently, little is known about comorbidities and the co-medication in these patients.ObjectivesTo explore the pattern of comorbidities and co-medication in PSP patients according to the known different phenotypes and in comparison with patients without neurodegenerative disease.MethodsCross-sectional data of PSP and patients without neurodegenerative diseases (non-ND) were collected from three German multicenter observational studies (DescribePSP, ProPSP and DANCER). The prevalence of comorbidities according to WHO ICD-10 classification and the prevalence of drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were evaluated using AiDKlinik (R).ResultsIn total, 335 PSP and 275 non-ND patients were included in this analysis. The prevalence of diseases of the circulatory and the nervous system was higher in PSP at first level of ICD-10. Dorsopathies, diabetes mellitus, other nutritional deficiencies and polyneuropathies were more frequent in PSP at second level of ICD-10. In particular, the summed prevalence of cardiovascular and cerebrovascular diseases was higher in PSP patients. More drugs were administered in the PSP group leading to a greater percentage of patients with polypharmacy. Accordingly, the prevalence of potential drug-drug interactions was higher in PSP patients, especially severe and moderate interactions.ConclusionsPSP patients possess a characteristic profile of comorbidities, particularly diabetes and cardiovascular diseases. The eminent burden of comorbidities and resulting polypharmacy should be carefully considered when treating PSP patients

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Effects of Voice Pitch on Social Perceptions Vary With Relational Mobility and Homicide Rate

Fundamental frequency ( fo) is the most perceptually salient vocal acoustic parameter, yet little is known about how its perceptual influence varies across societies. We examined how fo affects key social perceptions and how socioecological variables modulate these effects in 2,647 adult listeners sampled from 44 locations across 22 nations. Low male fo increased men’s perceptions of formidability and prestige, especially in societies with higher homicide rates and greater relational mobility in which male intrasexual competition may be more intense and rapid identification of high-status competitors may be exigent. High female fo increased women’s perceptions of flirtatiousness where relational mobility was lower and threats to mating relationships may be greater. These results indicate that the influence of fo on social perceptions depends on socioecological variables, including those related to competition for status and mates