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The Role of Clusterin Transporter in the Pathogenesis of Alzheimer’s Disease at the Blood-Brain Barrier Interface: A Systematic Review.

Alzheimer's disease (AD) is considered a chronic and debilitating neurological illness that is increasingly impacting older-age populations. Some proteins, including clusterin ( or ) transporter, can be linked to AD, causing oxidative stress. Therefore, its activity can affect various functions involving complement system inactivation, lipid transport, chaperone activity, neuronal transmission, and cellular survival pathways. This transporter is known to bind to the amyloid beta (Aβ) peptide, which is the major pathogenic factor of AD. On the other hand, this transporter is also active at the blood-brain barrier (BBB), a barrier that prevents harmful substances from entering and exiting the brain. Therefore, in this review, we discuss and emphasize the role of the transporter and -linked molecular mechanisms at the BBB interface in the pathogenesis of AD.

Effectiveness of Non-Pharmacological Methods, Such as Breastfeeding, to Mitigate Pain in NICU Infants.

Neonates do experience pain and its management is necessary in order to prevent long-term, as well as, short-term effects. The most common source of pain in the neonatal intensive care unit (NICU) is caused by medically invasive procedures. NICU patients have to endure trauma, medical adhesive related skin injuries, heel lance, venipuncture and intramuscular injection as well as nasogastric catheterization besides surgery. A cornerstone in pain assessment is the use of scales such as COMFORT, PIPP-R, NIPS and N-PASS. This narrative review provides an up to date account of neonate pain management used in NICUs worldwide focusing on non-pharmacological methods. Non-steroidal anti-inflammatory drugs have well established adverse side effects and opioids are addictive thus pharmacological methods should be avoided if possible at least for mild pain management. Non-pharmacological interventions, particularly breastfeeding and non-nutritive sucking as primary strategies for pain management in neonates are useful strategies to consider. The best non-pharmacological methods are breastfeeding followed by non-nutritive sucking coupled with sucrose sucking. Regrettably most parents used only physical methods and should be trained and involved for best results. Further research in NICU is essential as the developmental knowledge changes and neonate physiology is further uncovered together with its connection to pain.

The Feasibility and Acceptability of Resilience Coaching for Adolescent Chronic Musculoskeletal Pain: A Single-Arm Pilot Trial.

Promoting Resilience in Stress Management (PRISM) is a well-established resilience coaching program for youth with chronic illness. It is a one-on-one intervention targeting skills in stress management, goal-setting, cognitive reframing, and meaning-making. We aimed to (i) assess the feasibility and acceptability of PRISM and (ii) explore PRISM's impact on clinical outcomes among youth with chronic musculoskeletal pain (CMP). This was a single-arm pilot trial of PRISM for youth with CMP aged 12-17 years. Patients completed patient-reported outcome measures (PROs) pre- and post- intervention; patients and caregivers provided qualitative feedback. Twenty-seven patients were enrolled (63% enrollment rate); 82% percent were female. The patients' median age was 16 years (IQR: 13-16). The intervention completion rate was 81% ( = 22). The mean satisfaction for PRISM overall was 4.3 (SD 0.9), while the mean acceptability of the intervention measure (AIM) was 4.4 (SD 0.89). Participants reported improved resilience (2.2 [SD 5.1]), functional disability (-3.5 [IQR: -6.0, 1.0]), and psychological distress (-1.0 [-5.0, 2.0]) from baseline to immediately post-treatment; pain intensity, pain catastrophizing, and global health were similar at both time points. Feedback was positive and suggested that a group component may be helpful. PRISM is feasible and acceptable among youth with CMP. Exploratory analyses suggest improvements in clinically relevant outcomes, warranting further investigation.

Update on Non-Pharmacological Interventions for Treatment of Post-Traumatic Headache.

Post-traumatic headache (PTH) is the most common sequelae of traumatic brain injury (TBI). Its phenotypic variability, absence of formal evidence-based guidelines for treatment and underdiagnosis have made its management a challenge for clinicians. As a result, treatment of PTH has been mostly empiric. Although analgesics are the most popular drug of choice for PTH, they can present with several adverse effects and fail to address other psychosocial comorbidities associated with TBI. Non-pharmacological interventions thereby offer an intriguing alternative that can provide patients with PTH sustainable and effective care. This review article aims to: (1) provide an update on and describe different non-pharmacological interventions present in the recent literature; (2) provide clinical guidance to providers struggling with the management of patients with PTH; (3) emphasize the need for more high-quality trials examining the effectiveness of non-pharmacological treatments in patients with PTH. This review discusses 21 unique non-pharmacological treatments used for the management of PTH. Current knowledge of non-pharmacological interventions for the treatment of PTH is based on smaller scale studies, highlighting the need for larger randomized controlled trials to help establish formal evidence-based guidelines.

The ALFF Alterations of Spontaneous Pelvic Pain in the Patients of Chronic Prostatitis/Chronic Pelvic Pain Syndrome Evaluated by fMRI.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a challenging entity with complicated symptoms for treatment in the male crowd. Accumulating evidence revealed the dysfunction in the central system should be a critical factor for the pathogenesis and development in the CP/CPPS. Therefore, we recruited 20 patients of CP/CPPS and 20 healthy male volunteers, aged 20 to 50 years. Through resting-state functional magnetic resonance imaging (fMRI), we analyzed the mean amplitude of low-frequency fluctuations (mALFF) and the mean fractional amplitude of low-frequency fluctuations (mfALFF) to reflect the spontaneous abnormal activated regions in the brains of CP/CPPS patients. Compared to the healthy controls, the group with CP/CPPS had significantly increased mALFF values in the thalamus and augmented fALFF values in the inferior parietal lobule and cingulate gyrus. Significant positive correlations were observed in the extracted mALFF values in the midbrain periaqueductal gray matter (PAG) and the pain intensity ( = 0.2712, = 0.0019), mALFF values in the thalamus and the scores of Hospital Anxiety and Depression Scale (HADS) anxiety subscale ( = 0.08477, = 0.0461), and mfALFF values in the superior frontal gyrus (SFG) and the scores of the HADS anxiety subscale ( = 0.07102, = 0.0282). Therefore, we delineated the clinical alterations in patients of CP/CPPS that might be attributed to the functional abnormality of the thalamus, inferior parietal lobule, and cingulate gyrus. Among these regions, the PAG, thalamus, and SFG may further play an important role in the pathogenesis, with their regulating effect on pain or emotion.

“My Hand Is Different”: Altered Body Perception in Stroke Survivors with Chronic Pain.

Chronic pain and body perception disturbance are common following stroke. It is possible that an interaction exists between pain and body perception disturbance, and that a change in one may influence the other. We therefore investigated the presence of body perception disturbance in individuals with stroke, aiming to determine if a perceived change in hand size contralateral to the stroke lesion is more common in those with chronic pain than in those without.

Underlying Music Mechanisms Influencing the Neurology of Pain: An Integrative Model.

Pain is often debilitating, and is associated with many pathologies, as either a cause or consequence. Pharmacological interventions, such as opioids, to manage pain may lead to potential problems, such as addiction. When pain is controlled and managed, it can prevent negative associated outcomes affiliated with disease. Music is a low-cost option that shows promise in the management of painful circumstances. Music therapy has provided potent options for pain relief across a variety of ages and populations. As a nonpharmacological alternative or complement lacking side effects, music interventions are growing in clinical application and research protocols. This article considers the neurological implications of varying kinds of pain to provide working considerations that preempt the use of music and music-therapy applications in treating pain.

Reversible Splenial Lesion Syndrome (RESLES) after Nitrous Oxide Abuse: A Case Report.

Reversible splenial-lesion syndrome (RESLES) is a relatively rare and underrecognized clinical-imaging syndrome involving the splenium of the corpus callosum (SCC). RESLES can be caused by various etiologies.

Prolonged Suppression of Neuropathic Hypersensitivity upon Neurostimulation of the Posterior Insula in Mice.

Neurostimulation-based therapeutic approaches are emerging as alternatives to pharmacological drugs, but need further development to optimize efficacy and reduce variability. Despite its key relevance to pain, the insular cortex has not been explored in cortical neurostimulation approaches. Here, we developed an approach to perform repetitive transcranial direct current stimulation of the posterior insula (PI tDCS) and studied its impact on sensory and aversive components of neuropathic pain and pain-related anxiety and the underlying neural circuitry in mice using behavioral methods, pharmacological interventions and the expression of the activity-induced gene product, Fos. We observed that repetitive PI tDCS strongly attenuates the development of neuropathic mechanical allodynia and also reverses chronically established mechanical and cold allodynia for several weeks post-treatment by employing descending opioidergic antinociceptive pathways. Pain-related anxiety, but not pain-related aversion, were inhibited by PI tDCS. These effects were associated with a long-term suppression in the activity of key areas involved in pain modulation, such as the cingulate, prefrontal and motor cortices. These data uncover the significant potential of targeting the insular cortex with the objective of pain relief and open the way for more detailed mechanistic analyses that will contribute to improving cortical neurostimulation therapies for use in the clinical management of pain.

Febrile Seizures Cause Depression and Anxiogenic Behaviors in Rats.

Febrile seizure (FS) is a common type of seizure occurring in human during infancy and childhood. Although an epileptic seizure is associated with psychiatric disorders and comorbid diseases such as depression, anxiety, autism spectrum disorders, sleep disorders, attention deficits, cognitive impairment, and migraine, the causal relationship between FS and psychiatric disorders is poorly understood. The objective of the current study was to investigate the relationship of FS occurrence in childhood with the pathogenesis of anxiety disorder and depression using an FS rat model. We induced febrile seizures in infantile rats (11 days postnatal) using a mercury vapor lamp. At 3 weeks and 12 weeks after FS induction, we examined behaviors and recorded local field potentials (LFPs) to assess anxiety and depression disorder. Interestingly, after FS induction in infantile rats, anxiogenic behaviors and depression-like phenotypes were found in both adult and juvenile FS rats. The analysis of LFPs revealed that 4-7 Hz hippocampal theta rhythm, a neural oscillatory marker for anxiety disorder, was significantly increased in FS rats compared with their wild-type littermates. Taken together, our findings suggest that FS occurrence in infants is causally related to increased levels of anxiety-related behaviors and depression-like symptoms in juvenile and adult rodents.

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