The Relationship between Urinary Incontinence, Osteoarthritis, and Musculoskeletal System Disorders.

Background/Objectives: Urinary incontinence diminishes quality of life, and its severity can be worsened by mobility impairments. This study explored the link between urinary incontinence, osteoarthritis, and back musculoskeletal system disorders, considering pain, mobility issues, and daily activity difficulties. Methods: This cross-sectional study included respondents aged ≥ 15 years from the 2008 Turkish Health Studies Survey (n = 13,976). We assessed self-reported urinary incontinence, daily activity, mobility impairment, pain, osteoarthritis, and musculoskeletal disorders to explore their association with urinary incontinence. Gender-specific logistic regression models included chronic conditions related to urinary incontinence. Results: The prevalence of urinary incontinence was higher in the participants with osteoarthritis and back musculoskeletal system problems. Among the patients with osteoarthritis, the prevalence was 25.84% in the mobility-impaired group and 10.03% in the non-impaired group. Similarly, 33.02% of those with activities of daily living (ADL) difficulties and 12.93% of those without difficulties had incontinence. The frequency of urinary incontinence increased with pain severity. According to the multivariable logistic regression analyses, the adjusted odds ratio (95% confidence interval) of urinary incontinence for osteoarthritis was 1.58 (95% CI 1.23-2.02, p < 0.01) for females and 2.38 (95% CI 1.62-3.49, p < 0.01) for males. Conclusions: Urinary incontinence was more common in females, increased with age, and was found to be associated with osteoarthritis and back musculoskeletal system disorders. Among the patients with osteoarthritis and back musculoskeletal system disorders, those with mobility impairment and daily activity difficulties had a higher prevalence of urinary incontinence. The patients with more severe pain had a higher frequency of urinary incontinence.

Social isolation initiated post-weaning augments ischemic brain injury by promoting pro-inflammatory responses.

Social isolation is associated with poor stroke outcome, but the underlying molecular mechanisms were largely unknown. In male Balb/C mice exposed to transient middle cerebral artery occlusion (MCAo), we examined the effects of social isolation initiated post-weaning on ischemic injury, cytokine/chemokine responses and cell signaling using a broad panel of techniques that involved immunocytochemistry, cytokine/chemokine array and Western blots. Social isolation initiated post-weaning elevated infarct size, brain edema and neuronal injury in the ischemic brain tissue 3 days after MCAo, and increased microglia/ macrophage and leukocyte accumulation. In line with the increased immune cell recruitment, levels of several proinflammatory cytokines (e.g., IL-1α, IL-1ß, IL-13, IL-17, TNF-α, IFN-γ), chemokines (e.g., CCL3, CCL4, CCL12, CXCL2, CXCL9, CXCL12) and adhesion molecules (i.e., ICAM-1) were increased in the ischemic brain tissue of socially isolated compared with paired housing mice, whereas levels of selected cytokines (IL-5, IL-6, IL-16) and colony-stimulating factors (G-CSF, GM-CSF) were reduced. The activity of the transcription factor nuclear factor-ĸB (NF-ĸB), which promotes cell injury via pro-inflammatory responses, was increased by social isolation, whereas that of nuclear factor erythroid related factor-2 (Nrf-2), which mediates anti-oxidative responses under oxidative stress conditions, was reduced. Our study shows that social isolation profoundly alters post-ischemic cell signaling in a way promoting pro-inflammatory responses. Our results highlight the importance of social support in preventing deleterious health effects of social isolation.

When Bladder and Brain Collide: Is There a Gender Difference in the Relationship between Urinary Incontinence, Chronic Depression, and Anxiety?

In longitudinal and cross-sectional studies, depression and anxiety have been associated with urinary incontinence (UI) in women. However, this association has not been studied in men. Utilizing data from the 2008 Turkish Health Studies Survey conducted by the Turkish Statistical Institute, we analyzed 13,830 participants aged 15 years and above. We investigated the association of UI with psychological discomfort in both sexes using multivariable logistic regression. High psychological discomfort significantly correlated with UI in males (OR 2.30, 95% CI 1.43-3.71) and females (OR 2.78, 95% CI 1.80-4.29). Anxiety increased UI likelihood in females (OR 2.36, 95% CI 1.61-3.46) and males (OR 2.37, 95% CI 1.10-5.13). Depression related significantly to UI in females (OR 2.54, 95% CI 1.81-3.58) but not males (OR 1.63, 95% CI 0.71-3.76). Antidepressant and anxiolytic use was not significantly related to UI in either gender. Anxiety and psychological discomfort contribute to UI in both genders. While depression significantly correlates with UI in females, it does not show the same magnitude and significance in males. Antidepressant and anxiolytic use did not significantly influence the association. These findings underscore the psychological distress-UI link, advocating a holistic approach for managing UI in individuals with mental health conditions.

The Unconventional Growth Factors Cerebral Dopamine Neurotrophic Factor and Mesencephalic Astrocyte-Derived Neurotrophic Factor Promote Post-ischemic Neurological Recovery, Perilesional Brain Remodeling, and Lesion-Remote Axonal Plasticity.

Considerable efforts are currently made to develop strategies that boost endogenous recovery once a stroke has occurred. Owing to their restorative properties, neurotrophic factors are attractive candidates that capitalize on endogenous response mechanisms. Non-conventional growth factors cerebral dopamine neurotrophic factor (CDNF) and mesencephalic astrocyte-derived neurotrophic factor (MANF) promote neuronal survival and reduce neurological deficits in the acute phase of ischemic stroke in mice. Their effects on endogenous repair and recovery mechanisms in the stroke recovery phase were so far unknown. By intracerebroventricular delivery of CDNF or MANF starting 3 days post-stroke (1 µg/day for 28 days via miniosmotic pumps), we show that delayed CDNF and MANF administration promoted functional neurological recovery assessed by a battery of behavioral tests, increased long-term neuronal survival, reduced delayed brain atrophy, glial scar formation, and, in case of CDNF but not MANF, increased endogenous neurogenesis in the perilesional brain tissue. Besides, CDNF and MANF administration increased long-distance outgrowth of terminal axons emanating from the contralesional pyramidal tract, which crossed the midline to innervate ipsilesional facial nucleus. This plasticity promoting effect was accompanied by downregulation of the axonal growth inhibitor versican and the guidance molecules ephrin B1 and B2 in the previously ischemic hemisphere at 14 dpi, which represents a sensitive time-point for axonal growth. CDNF and MANF reduced the expression of the proinflammatory cytokines IL1ß and TNFα in both hemispheres. The effects of non-conventional growth factors in the ischemic brain should further be examined since they might help to identify targets for restorative stroke therapy.

A Novel Theanine Complex, Mg-L-Theanine Improves Sleep Quality via Regulating Brain Electrochemical Activity.

L-Theanine is commonly used to improve sleep quality through inhibitory neurotransmitters. On the other hand, Mg2+, a natural NMDA antagonist and GABA agonist, has a critical role in sleep regulation. Using the caffeine-induced brain electrical activity model, here we investigated the potency of L-theanine and two novel Mg-L-theanine compounds with different magnesium concentrations on electrocorticography (ECoG) patterns, GABAergic and serotonergic receptor expressions, dopamine, serotonin, and melatonin levels. Furthermore, we evaluated the sleep latency and duration in the pentobarbital induced sleep model. We herein showed that L-theanine, particularly its various complexes with magnesium increases the expression of GABAergic, serotonergic, and glutamatergic receptors, which were associated with decreased ECoG frequency, increased amplitude, and enhanced delta wave powers. Besides increased dopamine, serotonin, and melatonin; decreased MDA and increased antioxidant enzyme levels were also observed particularly with Mg-complexes. Protein expression analyses also showed that Mg-L-theanine complexes decrease inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) levels significantly. In accordance with these results, Mg complexes improved the sleep latency and duration even after caffeine administration. As a result, our data indicate that Mg-L-theanine compounds potentiate the effect of L-theanine on sleep by boosting slow-brain waves, regulating brain electrical activity, and increasing neurotransmitter and GABA receptor levels.

Phosphorylation of PI3K/Akt at Thr308, but not phosphorylation of MAPK kinase, mediates lithium-induced neuroprotection against cerebral ischemia in mice.

Lithium, in addition to its effect on acute and long-term bipolar disorder, is involved in neuroprotection after ischemic stroke. Yet, its mechanism of action is still poorly understood, which was only limited to its modulatory effect on GSK pathway. Therefore, we initially analyzed the dose-dependent effects of lithium on neurological deficits, infarct volume, brain edema and blood-brain barrier integrity, along with neuronal injury and survival in mice subjected to focal cerebral ischemia. Thereafter, we investigated the involvement of the PI3K/Akt and MEK signal transduction pathways and their components. Our observations revealed that 2 mmol/kg lithium significantly improved post-ischemic brain tissue survival. Although, 2 mmol/kg lithium had no negative effect on brain microcirculation, 5 and 20 mmol/kg lithium reduced brain perfusion. Furthermore, supratherapeutic dose of lithium in 20 mmol/kg lead to animal death. In addition, improvement of brain perfusion with L-arginine, did not change the effect of 5 mmol/kg lithium on brain injury. Additionally, post-stroke blood-brain barrier leakage, hemodynamic impairment and apoptosis have been reversed by lithium treatment. Interestingly, lithium-induced neuroprotection was associated with increased phosphorylation of Akt at Thr308 and suppressed GSK-3ß phosphorylation at Ser9 residue. Lithium upregulated Erk-2 and downregulated JNK-2 phosphorylation. To distinguish whether neuroprotective effects of lithium are modulated by PI3K/Akt or MEK, we sequentially blocked these pathways and demonstrated that the neuroprotective activity of lithium persisted during MEK/ERK inhibition, whereas PI3K/Akt inhibition abolished neuroprotection. Collectively, we demonstrated lithium exerts its post-stroke neuroprotective activity via the PI3K/Akt pathway, specifically via Akt phosphorylation at Thr308, but not via MEK/ERK.