Testicular Germ Cell Tumors in Children and Adolescents Treated With Bleomycin, Etoposide, and Cisplatin (BEP) Protocol: A Survival Analysis.

BACKGROUND: Germ cell tumors (GCTs) represent a diverse group of rare neoplasms that vary in location, histology, and clinical presentation. This study focuses on the clinical outcomes and survival rates of children and adolescents treated with the bleomycin, etoposide, and cisplatin (BEP) protocol. METHODS: This observational study evaluated children under 18 years diagnosed with testicular germ cell tumors and treated with the BEP protocol from January 2008 to December 2018. We employed descriptive analysis and used the Kaplan-Meier method to calculate event-free survival (EFS) and overall survival rates. RESULTS: The study included 32 patients with an average age of 9.8 years (SD ± 6.7). The primary reason for consultation was a testicular mass. The classification of patients was E-I for 14 patients (44%) and E-III and E-IV for nine patients (28%). Endodermal sinus tumors and mixed germ cell tumors were the most commonly identified histological types. With a median follow-up of 7.8 years (95% confidence interval {CI}: 5.9-9.6), the event-free survival was 63.7%. The overall survival at a median follow-up of 9.1 years (95% CI: 7.5-10.7) was 76.1%. CONCLUSION: The BEP chemotherapy regimen offers promising results for treating testicular germ cell tumors in children and adolescents, characterized by its low toxicity and minimal late side effects. However, patients older than 11 years displayed more adverse histological indicators, advanced disease stages, and higher relapse and mortality rates.

Vitaminas B neurotrópicas y neuropatía periférica: estado del arte y acuerdo de expertos / Neurotropic B vitamins and peripheral neuropathy: State of the art and agreement of experts

Propósito: La neuropatía periférica tiene un espectro clínico inespecífico y multifactorial, con frecuente subdiagnóstico y terapéutica de eficacia variable. Existe una heterogénea prescripción de vitaminas B, las cuales pueden desempeñar un rol importante en el manejo de diferentes neuropatías; sin embargo, en Colombia no existen guías clínicas al respecto. El propósito de este trabajo es orientar en el reconocimiento temprano de las neuropatías periféricas y generar recomendaciones sobre el uso adecuado de vitaminas B neurotrópicas. Descripción de la metodología: Acuerdo de expertos sobre la neuropatía periférica y el rol terapéutico de las vitaminas B con énfasis en la epidemiología en Colombia, diagnóstico y tratamiento. Contenidos: En Colombia, la prevalencia de neuropatía periférica se estima cercana al 10 %, sin embargo, no hay datos recientes. Dentro de las etiologías más frecuentes se encuentran la neuropatía diabética, infecciosa, inflamatoria, carenciales, toxica y farmacológica. Se recomiendan las siguientes herramientas de tamizaje en población de riesgo: DN4, MNSI, test de monofilamento, test de vibración y valoración de reflejos. Las vitaminas B1, B6 y B12 son seguras, accesibles y pueden ser eficaces en neuropatía periférica, incluso cuando el déficit no ha sido demostrado, pero con requerimientos particulares en su administración conjunta. Conclusiones: Las neuropatías periféricas son un reto diagnóstico y terapéutico que requiere la identificación oportuna para el tratamiento de la etiología subyacente y el control de síntomas. El uso de vitaminas B neurotrópicas es efectivo y seguro en neuropatía periférica carencial, y también parece ser eficaz en el manejo de neuropatías periféricas de diferentes etiologías.

Purpose: Peripheral neuropathy has a nonspecific and multifactorial clinical spectrum, with frequent underdiagnosis and therapeutics of variable efficacy. There is a high but heterogeneous prescription of B vitamins, which can play an important role in the management of different neuropathies; however, in Colombia there are no clinical guidelines in this regard. The purpose of this article is to guide the early recognition of peripheral neuropathy and generate recommendations on the proper use of neurotropic B vitamins. Description of the methodology: Expert agreement on peripheral neuropathy and the therapeutic role of B vitamins with emphasis on epidemiology in Colombia, diagnosis and treatment. Contents: In Colombia, there are no recent data to estimate the prevalence of peripheral neuropathy; the main etiologies are: diabetes mellitus, nutritional deficiencies, herpes zoster and neuropathies due to chemotherapy. Given risk factors in the anamnesis, the use of DN4, MNSI, monofilament test, vibration test and assessment of reflexes is recommended. Vitamins B1, B6, and B12 are safe and can be effective in peripheral neuropathy, even when the deficit has not been demonstrated, but with special requirements in their joint administration. Conclusions: peripheral neuropathies are a diagnostic and therapeutic challenge, and require timely identification, for the treatment of the underlying etiology and symptom control. The use of neurotropic B vitamins is effective and safe in deficient peripheral neuropathy, and also appears to be effective in the management of peripheral neuropathies of different etiologies.

Role of Calcium Modulation in the Pathophysiology and Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a chronic neurodegenerative disease and the most frequent cause of progressive dementia in senior adults. It is characterized by memory loss and cognitive impairment secondary to cholinergic dysfunction and N-methyl-D-aspartate (NMDA)-mediated neurotoxicity. Intracellular neurofibrillary tangles, extracellular plaques composed of amyloid-ß (Aß), and selective neurodegeneration are the anatomopathological hallmarks of this disease. The dysregulation of calcium may be present in all the stages of AD, and it is associated with other pathophysiological mechanisms, such as mitochondrial failure, oxidative stress, and chronic neuroinflammation. Although the cytosolic calcium alterations in AD are not completely elucidated, some calcium-permeable channels, transporters, pumps, and receptors have been shown to be involved at the neuronal and glial levels. In particular, the relationship between glutamatergic NMDA receptor (NMDAR) activity and amyloidosis has been widely documented. Other pathophysiological mechanisms involved in calcium dyshomeostasis include the activation of L-type voltage-dependent calcium channels, transient receptor potential channels, and ryanodine receptors, among many others. This review aims to update the calcium-dysregulation mechanisms in AD and discuss targets and molecules with therapeutic potential based on their modulation.

BOARD-FTD-PACC: a graphical user interface for the synaptic and cross-frequency analysis derived from neural signals.

In order to understand the link between brain functional states and behavioral/cognitive processes, the information carried in neural oscillations can be retrieved using different analytic techniques. Processing these different bio-signals is a complex, time-consuming, and often non-automatized process that requires customization, due to the type of signal acquired, acquisition method implemented, and the objectives of each individual research group. To this end, a new graphical user interface (GUI), named BOARD-FTD-PACC, was developed and designed to facilitate the visualization, quantification, and analysis of neurophysiological recordings. BOARD-FTD-PACC provides different and customizable tools that facilitate the task of analyzing post-synaptic activity and complex neural oscillatory data, mainly cross-frequency analysis. It is a flexible and user-friendly software that can be used by a wide range of users to extract valuable information from neurophysiological signals such as phase-amplitude coupling and relative power spectral density, among others. BOARD-FTD-PACC allows researchers to select, in the same open-source GUI, different approaches and techniques that will help promote a better understanding of synaptic and oscillatory activity in specific brain structures with or without stimulation.

Perceptions of Treatment Burden Among Caregivers of Elders With Diabetes and Co-morbid Alzheimer's Disease and Related Dementias: A Qualitative Study.

Many older adults with diabetes (DM) have co-occurring Alzheimer's Disease (AD) and AD-Related Dementias (ADRD). Complex treatment plans may impose treatment burden for caregivers responsible for day-to-day self-management. The purpose of this qualitative study was to describe caregiver perceptions of treatment burden for people with DM-AD/ADRD. Caregivers (n = 33) of patients with DM-AD/ADRD participated in semi-structured interviews about their caregiver role and perceptions of treatment burden of DM-AD/ADRD management. Qualitative data were analyzed using content analysis (ATLAS.ti). Caregivers reported high levels of burden related to complex treatment/self-management for patients with DM-AD/ADRD that varied day-to-day with the patient's cognitive status. Four themes were: (1) trajectory of treatment burden; (2) navigating multiple healthcare providers/systems of care; (3) caregiver role conflict; and (4) emotional burden. Interventions to reduce caregiver treatment burden should include activating supportive services, education, and care coordination especially, if patient treatment increases in complexity over time.

Astrocytes as a Therapeutic Target in Alzheimer's Disease-Comprehensive Review and Recent Developments.

Alzheimer's disease (AD) is a frequent and disabling neurodegenerative disorder, in which astrocytes participate in several pathophysiological processes including neuroinflammation, excitotoxicity, oxidative stress and lipid metabolism (along with a critical role in apolipoprotein E function). Current evidence shows that astrocytes have both neuroprotective and neurotoxic effects depending on the disease stage and microenvironmental factors. Furthermore, astrocytes appear to be affected by the presence of amyloid-beta (Aß), with alterations in calcium levels, gliotransmission and proinflammatory activity via RAGE-NF-κB pathway. In addition, astrocytes play an important role in the metabolism of tau and clearance of Aß through the glymphatic system. In this review, we will discuss novel pharmacological and non-pharmacological treatments focused on astrocytes as therapeutic targets for AD. These interventions include effects on anti-inflammatory/antioxidant systems, glutamate activity, lipid metabolism, neurovascular coupling and glymphatic system, calcium dysregulation, and in the release of peptides which affects glial and neuronal function. According to the AD stage, these therapies may be of benefit in either preventing or delaying the progression of the disease.

Factors associated with hospital admission and severe outcomes for older patients with COVID-19.

BACKGROUND: Morbidity and death due to coronavirus disease 2019 (COVID-19) experienced by older adults in nursing homes have been well described, but COVID-19's impact on community-living older adults is less studied. Similarly, the previous ambulatory care experience of such patients has rarely been considered in studies of COVID-19 risks and outcomes. METHODS: To investigate the relationship of advanced age (65+), on risk factors associated with COVID-19 outcomes in community-living elders, we identified an electronic health records cohort of older patients aged 65+ with laboratory-confirmed COVID-19 with and without an ambulatory care visit in the past 24 months (n = 47,219) in the New York City (NYC) academic medical institutions and the NYC public hospital system from January 2020 to February 2021. The main outcomes are COVID-19 hospitalization; severe outcomes/Intensive care unit (ICU), intubation, dialysis, stroke, in-hospital death), and in-hospital death. The exposures include demographic characteristics, and those with ambulatory records, comorbidities, frailty, and laboratory results. RESULTS: The 31,770 patients with an ambulatory history had a median age of 74 years; were 47.4% male, 24.3% non-Hispanic white, 23.3% non-Hispanic black, and 18.4% Hispanic. With increasing age, the odds ratios and attributable fractions of sex, race-ethnicity, comorbidities, and biomarkers decreased except for dementia and frailty (Hospital Frailty Risk Score). Patients without ambulatory care histories, compared to those with, had significantly higher adjusted rates of COVID-19 hospitalization and severe outcomes, with strongest effect in the oldest group. CONCLUSIONS: In this cohort of community-dwelling older adults, we provided evidence of age-specific risk factors for COVID-19 hospitalization and severe outcomes. Future research should explore the impact of frailty and dementia in severe COVID-19 outcomes in community-living older adults, and the role of engagement in ambulatory care in mitigating severe disease.

Geriatric Conditions Among Middle-aged and Older Adults on Methadone Maintenance Treatment: A Pilot Study.

OBJECTIVES: The number of older adults on methadone maintenance treatment (MMT) for opioid use disorder is increasing, but little is known about the characteristics and healthcare needs of this aging treatment population. This population may experience accelerated aging due to comorbidities and health behaviors. The aim of this study was to compare the prevalence of geriatric conditions among adults age ≥50 on MMT to a nationally representative sample of community-dwelling older adults. METHODS: We performed a geriatric assessment on 47 adults age ≥50 currently on MMT enrolled in 2 opioid treatment programs, in New York City and in East Providence, Rhode Island. We collected data on self-reported geriatric conditions, healthcare utilization, chronic medical conditions, physical function, and substance use. The results were compared to 470 age, sex, and race/ethnicity-matched adults in the national Health and Retirement Study. RESULTS: The mean age of the study sample was 58.8 years and 23.4% were female. The most common chronic diseases were hypertension (59.6%) and arthritis (55.3%) with 66% reporting ≥2 diseases. For geriatric conditions, adults on MMT had a significantly higher prevalence of mobility, hearing, and visual impairments as well as falls, urinary incontinence, chronic pain, and insomnia than the Health and Retirement Study sample. CONCLUSIONS: Older adults on MMT in 2 large opioid treatment programs have a high prevalence of geriatric conditions. An interdisciplinary, geriatric-based approach to care that focuses on function and addresses geriatric conditions is needed to improve the health of this growing population.

Guillain-Barré syndrome with bilateral facial diplegia secondary to severe acute respiratory syndrome coronavirus-2 infection: a case report.

BACKGROUND: The new coronavirus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) owing to its similarity to the previous severe acute respiratory syndrome (SARS), is characterized by causing, in most patients, nonspecific symptoms similar to those of the common flu. It has been reported that many coronavirus disease 2019 (COVID-19) patients presented neurological symptoms that involve the central and peripheral nervous systems. In addition, there have been several reports of patients who presented Guillain-Barré syndrome related to  COVID-19 , with sensory and motor compromise in the extremities. CASE PRESENTATION: In this report, we describe a rare case of Guillain-Barré syndrome in a 50-year-old Hispanic male with bilateral facial palsy as the only neurological manifestation, following SARS-CoV-2 infection. A complete neurophysiological study showed severe axonal neuropathy of the right and left facial nerves. CONCLUSION: Regardless of severity, clinicians must to be aware of any neurological manifestation generated by COVID-19 and start performing more neurophysiological tests to determine if the infection induces an axonal, myelin, or mixed involvement of the peripheral nervous system.

G-Protein-Gated Inwardly Rectifying Potassium (Kir3/GIRK) Channels Govern Synaptic Plasticity That Supports Hippocampal-Dependent Cognitive Functions in Male Mice.

The G-protein-gated inwardly rectifying potassium (Kir3/GIRK) channel is the effector of many G-protein-coupled receptors (GPCRs). Its dysfunction has been linked to the pathophysiology of Down syndrome, Alzheimer's and Parkinson's diseases, psychiatric disorders, epilepsy, drug addiction, or alcoholism. In the hippocampus, GIRK channels decrease excitability of the cells and contribute to resting membrane potential and inhibitory neurotransmission. Here, to elucidate the role of GIRK channels activity in the maintenance of hippocampal-dependent cognitive functions, their involvement in controlling neuronal excitability at different levels of complexity was examined in C57BL/6 male mice. For that purpose, GIRK activity in the dorsal hippocampus CA3-CA1 synapse was pharmacologically modulated by two drugs: ML297, a GIRK channel opener, and Tertiapin-Q (TQ), a GIRK channel blocker. Ex vivo, using dorsal hippocampal slices, we studied the effect of pharmacological GIRK modulation on synaptic plasticity processes induced in CA1 by Schaffer collateral stimulation. In vivo, we performed acute intracerebroventricular (i.c.v.) injections of the two GIRK modulators to study their contribution to electrophysiological properties and synaptic plasticity of dorsal hippocampal CA3-CA1 synapse, and to learning and memory capabilities during hippocampal-dependent tasks. We found that pharmacological disruption of GIRK channel activity by i.c.v. injections, causing either function gain or function loss, induced learning and memory deficits by a mechanism involving neural excitability impairments and alterations in the induction and maintenance of long-term synaptic plasticity processes. These results support the contention that an accurate control of GIRK activity must take place in the hippocampus to sustain cognitive functions.SIGNIFICANCE STATEMENT Cognitive processes of learning and memory that rely on hippocampal synaptic plasticity processes are critically ruled by a finely tuned neural excitability. G-protein-gated inwardly rectifying K+ (GIRK) channels play a key role in maintaining resting membrane potential, cell excitability and inhibitory neurotransmission. Here, we demonstrate that modulation of GIRK channels activity, causing either function gain or function loss, transforms high-frequency stimulation (HFS)-induced long-term potentiation (LTP) into long-term depression (LTD), inducing deficits in hippocampal-dependent learning and memory. Together, our data show a crucial GIRK-activity-mediated mechanism that governs synaptic plasticity direction and modulates subsequent hippocampal-dependent cognitive functions.

Acute Effects of Two Different Species of Amyloid-ß on Oscillatory Activity and Synaptic Plasticity in the Commissural CA3-CA1 Circuit of the Hippocampus.

Recent evidence indicates that soluble amyloid-ß (Aß) species induce imbalances in excitatory and inhibitory transmission, resulting in neural network functional impairment and cognitive deficits during early stages of Alzheimer's disease (AD). To evaluate the in vivo effects of two soluble Aß species (Aß 25-35 and Aß 1-40) on commissural CA3-to-CA1 (cCA3-to-CA1) synaptic transmission and plasticity, and CA1 oscillatory activity, we used acute intrahippocampal microinjections in adult anaesthetized male Wistar rats. Soluble Aß microinjection increased cCA3-to-CA1 synaptic variability without significant changes in synaptic efficiency. High-frequency CA3 stimulation was rendered inefficient by soluble Aß intrahippocampal injection to induce long-term potentiation and to enhance synaptic variability in CA1, contrasting with what was observed in vehicle-injected subjects. Although soluble Aß microinjection significantly increased the relative power of γ-band and ripple oscillations and significantly shifted the average vector of θ-to-γ phase-amplitude coupling (PAC) in CA1, it prevented θ-to-γ PAC shift induced by high-frequency CA3 stimulation, opposite to what was observed in vehicle-injected animals. These results provide further evidence that soluble Aß species induce synaptic dysfunction causing abnormal synaptic variability, impaired long-term plasticity, and deviant oscillatory activity, leading to network activity derailment in the hippocampus.

Update on Safety Profiles of Vitamins B1, B6, and B12: A Narrative Review.

The neurotropic B vitamins B1 (thiamine), B6 (pyridoxine), and B12 (cobalamin) are essential for proper functioning of the nervous system. Deficiencies may induce neurological disorders like peripheral neuropathy (PN) and mainly occur in vulnerable populations (eg, elderly, diabetics, alcoholics). As epidemiologic cohort studies raised safety concerns about vitamin B6/B12 intake being potentially associated with increased risks of hip fracture (HF) and lung cancer (LC), we explored these aspects and performed comprehensive literature searches. However, we suggest not to neglect actual high-risk factors (eg, smoking in LC, higher age in HF) by focusing on individual nutrients, but to examine the complex interaction of numerous factors involved in disease development. Because it warrants continued consideration, we also provide an update on neurotoxicity associated with vitamin B6. We consider that neurological side effects due to vitamin B6 intake are rare and only occur with high daily doses and/or longer treatment duration. The benefit-risk ratio of high-dose treatment with neurotropic B vitamins in indications like PN is therefore considered advantageous, particularly if dosing recommendations are followed and serum levels monitored.

Co-occurring mental illness, drug use, and medical multimorbidity among lesbian, gay, and bisexual middle-aged and older adults in the United States: a nationally representative study.

BACKGROUND: Older lesbian, gay, and bisexual (LGB) adults are an underserved and understudied population that experience specific health disparities. The intersection of aging and chronic medical disease with a higher risk for substance use and mental illness may place older LGB adults at risk for co-occurring conditions and resulting comorbidity. Understanding multimorbidity among older LGB adults may help inform interventions to reduce disparities in health outcomes. METHODS: Data come from the 2015 to 2017 National Surveys on Drug Use and Health (n = 25,880). We first determined whether sexual orientation was associated with reporting: past-year drug use, mental illness, and/or 2 or more chronic medical diseases. We then determined whether sexual orientation was associated with reporting co-occurrence of these conditions. This was done using multivariable logistic regression. Analyses were stratified by gender. RESULTS: Compared to heterosexual men, gay men were at increased odds for reporting 2 or more chronic medical diseases (adjusted odds ratio [aOR] = 2.18, 95% confidence interval [CI] = 1.48, 3.21), and gay (aOR = 1.79, 95% CI = 1.09, 2.93) and bisexual men (aOR = 3.53, 95% CI = 2.03, 6.14) were at increased odds for reporting mental illness. Gay men (aOR = 2.95, 95CI = 1.60, 5.49) and bisexual men (aOR = 2.84, 95% CI = 1.58, 5.08) were at increased odds of reporting co-occurring conditions. Compared to heterosexual women, bisexual women were at increased odds for past-year drug use (aOR = 4.20, 95% CI = 2.55, 6.93), reporting mental illness (aOR = 1.94, 95% CI = 1.03, 3.67), and reporting co-occurring conditions (aOR = 3.25, 95% = 1.60, 6.62). CONCLUSIONS: Middle-aged and older LGB adults in the United States are at high risk for experiencing co-occurring drug use, mental illness, and/or medical multimorbidity. Interventions for older sexual minority populations are needed to reduce disparities.

Apparent False Lateralization of Seizure Onset by Scalp EEG in Temporal Lobe Epilepsy Associated with Cerebral Cavernous Malformation: A Case Report and Overview.

False lateralization of ictal onset by scalp electroencephalogram (EEG) is an infrequent entity that has been reported in patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (HS). In these cases, a tendency for rapid seizures that spread through the frontal-limbic system and hippocampal commissural pathways to the contralateral hemisphere has been proposed. Cerebral cavernous malformations (CCMs), which constitute a collection of abnormally configured small blood vessels with irregular structures, is a well-defined epilepsy-associated pathology. Their primary association with seizures might be explained either as a result of physiological changes affecting the cerebral cortex immediately surrounding the CCM (an epileptogenic mechanism that is relevant for both, temporal and extratemporal lesions) or as a result of promoting epileptogenicity in remote but anatomo-functionally connected brain regions, a mechanism that is particularly relevant for temporal lobe lesions. To date, there have been only two publications on falsely lateralizing ictal onsets by EEG in temporal cavernoma, but not in other regions. Here, we report a rare case of apparent false lateralization of ictal onset by scalp EEG in a patient with a left medial frontal gyrus cavernoma (supplementary motor area), and discuss some relevant pathophysiological mechanisms of false lateralization.

Pathophysiological Mechanisms of Cognitive Impairment and Neurodegeneration by Toxoplasma gondii Infection.

Toxoplasma gondii is an obligate intracellular parasite considered one of the most successful pathogens in the world, owing to its ability to produce long-lasting infections and to persist in the central nervous system (CNS) in most warm-blooded animals, including humans. This parasite has a preference to invade neurons and affect the functioning of glial cells. This could lead to neurological and behavioral changes associated with cognitive impairment. Although several studies in humans and animal models have reported controversial results about the relationship between toxoplasmosis and the onset of dementia as a causal factor, two recent meta-analyses have shown a relative association with Alzheimer's disease (AD). AD is characterized by amyloid-ß (Aß) peptide accumulation, neurofibrillary tangles, and neuroinflammation. Different authors have found that toxoplasmosis may affect Aß production in brain areas linked with memory functioning, and can induce a central immune response and neurotransmitter imbalance, which in turn, affect the nervous system microenvironment. In contrast, other studies have revealed a reduction of Aß plaques and hyperphosphorylated tau protein formation in animal models, which might cause some protective effects. The aim of this article is to summarize and review the newest data in regard to different pathophysiological mechanisms of cerebral toxoplasmosis and their relationship with the development of AD and cognitive impairment. All these associations should be investigated further through clinical and experimental studies.

Effect of Combined Diclofenac and B Vitamins (Thiamine, Pyridoxine, and Cyanocobalamin) for Low Back Pain Management: Systematic Review and Meta-analysis.

BACKGROUND: Cumulative evidence suggests an analgesic effect of thiamine, pyridoxine, and cyanocobalamin (TPC) in monotherapy, and also when combined with nonsteroidal anti-inflammatory drugs (NSAIDs), particularly diclofenac, in a synergistic manner. The aim of this review was to determine the effects of diclofenac combined with TPC compared with diclofenac monotherapy for low back pain (LBP) management. METHODS: We searched for randomized clinical trials on the MEDLINE, EMBASE, LILACS, and Cochrane databases of records of clinical trials, among other sources. We evaluated the risk of bias regarding randomization, allocation concealment, blinding, incomplete outcome data, selective reporting, and other biases. A random-effects meta-analysis to examine patients with acute LBP (N = 1,108 adults) was performed, along with a subsequent sensitivity analysis. RESULTS: Five studies in patients with LBP were included in the qualitative synthesis. Four of these studies in acute LBP were included in the first meta-analysis. A sensitivity test based on risk of bias (three moderate- to high-quality studies) found that the combination therapy of diclofenac plus TPC was associated with a significant reduction in the duration of treatment (around 50%) compared with diclofenac monotherapy (odds ratio = 2.23, 95% confidence interval = 1.59 to 3.13, P < 0.00001). We found no differences in the safety profile and patient satisfaction. CONCLUSIONS: This meta-analysis demonstrated that combination therapy of diclofenac with TPC might have an analgesic superiority compared with diclofenac monotherapy in acute LBP. However, there is not enough evidence to recommend this therapy in other types of pain due to the scarcity of high-quality studies.

B Vitamins in the nervous system: Current knowledge of the biochemical modes of action and synergies of thiamine, pyridoxine, and cobalamin.

BACKGROUND: Neurotropic B vitamins play crucial roles as coenzymes and beyond in the nervous system. Particularly vitamin B1 (thiamine), B6 (pyridoxine), and B12 (cobalamin) contribute essentially to the maintenance of a healthy nervous system. Their importance is highlighted by many neurological diseases related to deficiencies in one or more of these vitamins, but they can improve certain neurological conditions even without a (proven) deficiency. AIM: This review focuses on the most important biochemical mechanisms, how they are linked with neurological functions and what deficits arise from malfunctioning of these pathways. DISCUSSION: We discussed the main role of B Vitamins on several functions in the peripheral and central nervous system (PNS and CNS) including cellular energetic processes, antioxidative and neuroprotective effects, and both myelin and neurotransmitter synthesis. We also provide an overview of possible biochemical synergies between thiamine, pyridoxine, and cobalamin and discuss by which major roles each of them may contribute to the synergy and how these functions are inter-related and complement each other. CONCLUSION: Taking into account the current knowledge on the neurotropic vitamins B1, B6, and B12, we conclude that a biochemical synergy becomes apparent in many different pathways in the nervous system, particularly in the PNS as exemplified by their combined use in the treatment of peripheral neuropathy.

The opioid system in stress-induced memory disorders: From basic mechanisms to clinical implications in post-traumatic stress disorder and Alzheimer's disease.

Cognitive and emotional impairment are a serious consequence of stress exposure and are core features of neurological and psychiatric conditions that involve memory disorders. Indeed, acute and chronic stress are high-risk factors for the onset of post-traumatic stress disorder (PTSD) and Alzheimer's disease (AD), two devastating brain disorders associated with memory dysfunction. Besides the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis, stress response also involves the activation of the opioid system in brain regions associated with stress regulation and memory processing. In this context, it is possible that stress-induced memory disorders may be attributed to alterations in the interaction between the neuroendocrine stress system and the opioid system. In this review, we: (1) describe the effects of acute and chronic stress on memory, and the modulatory role of the opioid system, (2) discuss the contribution of the opioid system to the pathophysiology of PTSD and AD, and (3) present evidence of current and potential therapies that target the opioid receptors to treat PTSD- and AD-associated symptoms.

Visual Features in Alzheimer's Disease: From Basic Mechanisms to Clinical Overview.

Alzheimer's disease (AD) is the leading cause of dementia worldwide. It compromises patients' daily activities owing to progressive cognitive deterioration, which has elevated direct and indirect costs. Although AD has several risk factors, aging is considered the most important. Unfortunately, clinical diagnosis is usually performed at an advanced disease stage when dementia is established, making implementation of successful therapeutic interventions difficult. Current biomarkers tend to be expensive, insufficient, or invasive, raising the need for novel, improved tools aimed at early disease detection. AD is characterized by brain atrophy due to neuronal and synaptic loss, extracellular amyloid plaques composed of amyloid-beta peptide (Aß), and neurofibrillary tangles of hyperphosphorylated tau protein. The visual system and central nervous system share many functional components. Thus, it is plausible that damage induced by Aß, tau, and neuroinflammation may be observed in visual components such as the retina, even at an early disease stage. This underscores the importance of implementing ophthalmological examinations, less invasive and expensive than other biomarkers, as useful measures to assess disease progression and severity in individuals with or at risk of AD. Here, we review functional and morphological changes of the retina and visual pathway in AD from pathophysiological and clinical perspectives.