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Dermatology Practical & Conceptual Jan 2024Diffuse Melanosis Cutis (DMC) is a rare and late complication of metastatic malignant melanoma (MM) characterized by progressive pigmentation of skin and sometimes... (Review)
Review
INTRODUCTION
Diffuse Melanosis Cutis (DMC) is a rare and late complication of metastatic malignant melanoma (MM) characterized by progressive pigmentation of skin and sometimes mucous membranes. The distinctive feature is the widespread and progressive deposition of melanin precursors in the dermis.
OBJECTIVES
The purpose of this review is to define the clinical and demographic features of DMC and to promote a deeper insight into the clinical manifestation, histological findings, and pathophysiology behind DMC.
METHODS
We have conducted a systematic review of the literature on published DMC in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. We also reported a case of DMC secondary to low-risk melanoma.
RESULTS
Overall, including our case report, we reported 53 articles described 62 DMC patients. Breslow level of primary melanoma was reported having a mean value of 3.3 mm. The mean survival rate from onset of DMC resulted being 4.36 months.
CONCLUSIONS
Among the most widely accepted etiopathogenetic hypotheses are deposition of melanic precursors in the dermis following tumor lysis, melanocyte proliferation induced by neoplastic growth factors, and the presence of diffuse dermal micro-metastases of MM. However, unanimous consensus on the proposed etiopathogenetic models of DMC is still lacking.
PubMed: 38364426
DOI: 10.5826/dpc.1401a8 -
Neuroscience and Biobehavioral Reviews Apr 2024Neuroscience has contributed to uncover the mechanisms underpinning substance use disorders (SUD). The next frontier is to leverage these mechanisms as active targets to... (Review)
Review
Neuroscience has contributed to uncover the mechanisms underpinning substance use disorders (SUD). The next frontier is to leverage these mechanisms as active targets to create more effective interventions for SUD treatment and prevention. Recent large-scale cohort studies from early childhood are generating multiple levels of neuroscience-based information with the potential to inform the development and refinement of future preventive strategies. However, there are still no available well-recognized frameworks to guide the integration of these multi-level datasets into prevention interventions. The Research Domain Criteria (RDoC) provides a neuroscience-based multi-system framework that is well suited to facilitate translation of neurobiological mechanisms into behavioral domains amenable to preventative interventions. We propose a novel RDoC-based framework for prevention science and adapted the framework for the existing preventive interventions. From a systematic review of randomized controlled trials using a person-centered drug/alcohol preventive approach for adolescents, we identified 22 unique preventive interventions. By teasing apart these 22 interventions into the RDoC domains, we proposed distinct neurocognitive trajectories which have been recognized as precursors or risk factors for SUDs, to be targeted, engaged and modified for effective addiction prevention.
Topics: Child, Preschool; Adolescent; Humans; Substance-Related Disorders; Neurosciences; Behavior, Addictive; Neurobiology
PubMed: 38360332
DOI: 10.1016/j.neubiorev.2024.105578 -
Neurobiology of Disease Mar 2024Transgenic models of familial Alzheimer's disease (AD) serve as valuable tools for probing the molecular mechanisms associated with amyloid-beta (Aβ)-induced pathology.... (Meta-Analysis)
Meta-Analysis Review
Transgenic models of familial Alzheimer's disease (AD) serve as valuable tools for probing the molecular mechanisms associated with amyloid-beta (Aβ)-induced pathology. In this meta-analysis, we sought to evaluate levels of phosphorylated tau (p-tau) and explore potential age-related variations in tau hyperphosphorylation, within mouse models of AD. The PubMed and Scopus databases were searched for studies measuring soluble p-tau in 5xFAD, APP/PSEN1, J20 and APP23 mice. Data were extracted and analyzed using standardized procedures. For the 5xFAD model, the search yielded 36 studies eligible for meta-analysis. Levels of p-tau were higher in 5xFAD mice relative to control, a difference that was evident in both the carboxy-terminal (CT) and proline-rich (PR) domains of tau. Age negatively moderated the relationship between genotype and CT phosphorylated tau in studies using hybrid mice, female mice, and preparations from the neocortex. For the APP/PSEN1 model, the search yielded 27 studies. Analysis showed tau hyperphosphorylation in transgenic vs. control animals, evident in both the CT and PR regions of tau. Age positively moderated the relationship between genotype and PR domain phosphorylated tau in the neocortex of APP/PSEN1 mice. A meta-analysis was not performed for the J20 and APP23 models, due to the limited number of studies measuring p-tau levels in these mice (<10 studies). Although tau is hyperphosphorylated in both 5xFAD and APP/PSEN1 mice, the effects of ageing on p-tau are contingent upon the model being examined. These observations emphasize the importance of tailoring model selection to the appropriate disease stage when considering the relationship between Aβ and tau, and suggest that there are optimal intervention points for the administration of both anti-amyloid and anti-tau therapies.
Topics: Mice; Female; Animals; Alzheimer Disease; Phosphorylation; Amyloid beta-Protein Precursor; Mice, Transgenic; tau Proteins; Amyloid beta-Peptides; Disease Models, Animal
PubMed: 38307366
DOI: 10.1016/j.nbd.2024.106427 -
Frontiers in Pharmacology 2023Berberine is an isoquinoline alkaloid extracted from Berberis vulgaris, which possesses a variety of pharmacological activities. Alzheimer's disease (AD) is a complex...
Berberine is an isoquinoline alkaloid extracted from Berberis vulgaris, which possesses a variety of pharmacological activities. Alzheimer's disease (AD) is a complex disease with multiple pathologic factors, with cognitive decline being the main manifestation of AD. The neuroprotective effects of berberine in animal models of Alzheimer's disease (AD) have been widely reported, exhibiting protective effects against risk factors associated with AD. In this study, we summarize and evaluate the effects of berberine on cognitive function and β-amyloid precursor protein in animal models of AD. Eligible studies were retrieved from PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Library databases up to 1 June 2023. Risk of bias was assessed by the Systematic Review Center for Laboratory Animal Experiments (SYRCLE). Statistical analyses were performed using STATA 14.0 and Review Manger 5.4 software to calculate weighted standardized mean difference (SMD) and 95% confidence intervals (CI), Morris water maze (MWM) test and β-amyloid precursor protein as outcome measures. Heterogeneity was tested using the I test. Sensitivity analysis and publication bias were also assessed. 19 studies involving 360 animals met the inclusion criteria, and the results of the meta-analysis showed that berberine decreased escape latency (SMD = -2.19, 95% CI: (-2.50, -1.88), < 0.00001), increased the number of platform crossings (SMD = 4.27, 95% CI (3.38, 5.17), < 0.00001), time in the target quadrant (SMD = 5.92, 95% CI (4.43, 7.41), < 0.00001) and APP expression (SMD = 0.73, 95% CI: (0.25, 1.21), = 0.003). Berberine can regulate APP expression and improve cognitive function in animal models of AD, and the mechanism may be related to the involvement of berberine in APP processing and influence the expression of its related factors. PROSPERO, CRD42023437445.
PubMed: 38293672
DOI: 10.3389/fphar.2023.1301102 -
Frontiers in Pharmacology 2023Recently, multiple preclinical studies have reported the beneficial effect of berberine in the treatment of Alzheimer's disease (AD). Nevertheless, the neuroprotective...
Recently, multiple preclinical studies have reported the beneficial effect of berberine in the treatment of Alzheimer's disease (AD). Nevertheless, the neuroprotective effects and possible mechanisms of berberine against AD are not universally recognized. This study aimed to conduct a systematic review and meta-analysis by integrating relevant animal studies to assess the neuroprotective effects and potential mechanisms of berberine on AD. We systematically searched PubMed, Embase, Scopus and Web of Science databases that reported the effects of berberine on AD models up to 1 February 2023. The escape latency, times of crossing platform, time spent in the target quadrant and pro-oligomerized amyloid beta 42 (Aβ) were included as primary outcomes. The secondary outcomes were the Tau-ps 204, Tau-ps 404, β-site of APP cleaving enzyme (BACE1), amyloid precursor protein (APP), acetylcholine esterase (AChE), tumor necrosis factor ⍺ (TNF-α), interleukin 1β (IL-1β), IL-6, nitric oxide (NO), glial fibrillary acidic protein (GFAP), malonaldehyde (MDA), glutathione S-transferase (GST), glutathione (GSH), glutathione peroxidase (GPx), Beclin-1 and neuronal apoptosis cells. This meta-analysis was conducted using RevMan 5.4 and STATA 15.1. The SYRCLE's risk of bias tool was used to assess the methodological quality. Twenty-two studies and 453 animals were included in the analysis. The overall results showed that berberine significantly shortened the escape latency ( < 0.00001), increased times of crossing platform ( < 0.00001) and time spent in the target quadrant ( < 0.00001), decreased Aβ deposition ( < 0.00001), Tau-ps 202 ( < 0.00001) and Tau-ps 404 ( = 0.002), and improved BACE1, APP, AChE, Beclin-1, neuronal apoptosis cells, oxidative stress and inflammation levels. Berberine may be a promising drug for the treatment of AD based on preclinical evidence (especially when the dose was 5-260 mg/kg). The potential mechanisms for these protective effects may be closely related to anti-neuroinflammation, anti-oxidative stress, modulation of autophagy, inhibition of neuronal apoptosis and protection of cholinergic system. However, these results may be limited by the quality of existing research. Larger and methodologically more rigorous preclinical research are needed to provide more convincing evidence.
PubMed: 38259291
DOI: 10.3389/fphar.2023.1287750 -
Biomedicines Jan 2024Acute myeloid leukemia (AML) is a diverse group of leukemias characterized by the uncontrolled proliferation of clonal neoplastic hematopoietic precursor cells with... (Review)
Review
Acute myeloid leukemia (AML) is a diverse group of leukemias characterized by the uncontrolled proliferation of clonal neoplastic hematopoietic precursor cells with chromosomal rearrangements and multiple gene mutations and the impairment of normal hematopoiesis. Current efforts to improve AML outcomes have focused on developing targeted therapies that may allow for improved antileukemic effects while reducing toxicity significantly. Gemtuzumab ozogamicin (GO) is one of the most thoroughly studied molecularly targeted therapies in adults. GO is a monoclonal antibody against CD33 IgG4 linked to the cytotoxic drug calicheamicin DMH. The use of GO as a chemotherapeutic agent is not generalized for all patients who suffer from AML, particularly for those whose health prevents them from using intensive conventional chemotherapy, in which case it can be used on its own, and those who have suffered a first relapse, where its combination with other chemotherapeutic agents is possible. This systematic review aimed to comprehensively evaluate GO, focusing on its molecular structure, mode of action, pharmacokinetics, recommended dosage, resistance mechanisms, and associated toxicities to provide valuable information on the potential benefits and risks associated with its clinical use. A systematic review of eight scientific articles from 2018 to 2023 was conducted using PRISMA analysis. The results showed that GO treatment activates proapoptotic pathways and induces double-strand breaks, initiating DNA repair mechanisms. Cells defective in DNA repair pathways are susceptible to GO cytotoxicity. GO has recommended doses for newly diagnosed CD33+ AML in combination or as a single agent. Depending on the treatment regimen and patient status, GO doses vary for induction, consolidation, and continuation cycles. Multidrug resistance (MDR) involving P-glycoprotein (P-gp) is associated with GO resistance. The overexpression of P-gp reduces GO cytotoxicity; inhibitors of P-gp can restore sensitivity. Mitochondrial pathway activation and survival signaling pathways are linked to GO resistance. Other resistance mechanisms include altered pharmacokinetics, reduced binding ability, and anti-apoptotic mechanisms. GO has limited extramedullary toxicity compared to other AML treatments and may cause hepatic veno-occlusive disease (HVOD). The incidence of hepatic HVOD after GO therapy is higher in patients with high tumor burden. Hematological side effects and hepatotoxicity are prominent, with thrombocytopenia and neutropenia observed. In conclusion, GO's reintroduction in 2017 followed a thorough FDA review considering its altered dose, dosing schedule, and target population. The drug's mechanism involves CD33 targeting and calicheamicin-induced DNA damage, leading to apoptosis and resistance mechanisms, including MDR and survival signaling, which impact treatment outcomes. Despite limited extramedullary toxicity, GO is associated with hematological side effects and hepatotoxicity.
PubMed: 38255313
DOI: 10.3390/biomedicines12010208 -
Scientific Reports Jan 2024Cardiac magnetic resonance (CMR) is the gold standard for the diagnostic classification and risk stratification in most patients with cardiac disorders. The aim of the... (Meta-Analysis)
Meta-Analysis
Cardiac magnetic resonance (CMR) is the gold standard for the diagnostic classification and risk stratification in most patients with cardiac disorders. The aim of the present study was to investigate the ability of Strain-encoded MR (SENC) for the prediction of major adverse cardiovascular events (MACE). A systematic review and meta-analysis was performed according to the PRISMA Guidelines, including patients with or without cardiovascular disease and asymptomatic individuals. Myocardial strain by HARP were used as pulse sequences in 1.5 T scanners. Published literature in MEDLINE (PubMed) and Cochrane's databases were explored before February 2023 for studies assessing the clinical utility of myocardial strain by Harmonic Phase Magnetic Resonance Imaging (HARP), Strain-encoded MR (SENC) or fast-SENC. In total, 8 clinical trials (4 studies conducted in asymptomatic individuals and 4 in patients with suspected or known cardiac disease) were included in this systematic review, while 3 studies were used for our meta-analysis, based on individual patient level data. Kaplan-Meier analysis and Cox proportional hazard models were used, testing the ability of myocardial strain by HARP and SENC/fast-SENC for the prediction of MACE. Strain enabled risk stratification in asymptomatic individuals, predicting MACE and the development of incident heart failure. Of 1332 patients who underwent clinically indicated CMR, including SENC or fast-SENC acquisitions, 19 patients died, 28 experienced non-fatal infarctions, 52 underwent coronary revascularization and 86 were hospitalized due to heart failure during median 22.4 (17.2-28.5) months of follow-up. SENC/fast-SENC, predicted both all-cause mortality and MACE with high accuracy (HR = 3.0, 95% CI = 1.2-7.6, p = 0.02 and HR = 4.1, 95% CI = 3.0-5.5, respectively, p < 0.001). Using hierarchical Cox-proportional hazard regression models, SENC/fast-SENC exhibited incremental value to clinical data and conventional CMR parameters. Reduced myocardial strain predicts of all-cause mortality and cardiac outcomes in symptomatic patients with a wide range of ischemic or non-ischemic cardiac diseases, whereas in asymptomatic individuals, reduced strain was a precursor of incident heart failure.
Topics: Humans; Magnetic Resonance Imaging, Cine; Heart; Magnetic Resonance Imaging; Heart Diseases; Heart Failure; Magnetic Resonance Spectroscopy; Predictive Value of Tests; Prognosis
PubMed: 38212323
DOI: 10.1038/s41598-023-50835-5 -
Intensive & Critical Care Nursing Apr 2024To critically summarise the qualitative literature to understand patients' experiences of delusional memories during their Intensive Care Unit stay. (Review)
Review
OBJECTIVE
To critically summarise the qualitative literature to understand patients' experiences of delusional memories during their Intensive Care Unit stay.
RESEARCH METHODOLOGY
A systematic review of qualitative studies with meta-synthesis and meta-summary. We searched MEDLINE (via PubMed), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and Web of Science to July 2022. All studies that provided qualitative insights into the subjective experience of adult patients with delusional memories in the Intensive Care Unit were selected. The Critical Assessment Skills Programme checklist was used for the quality assessment.
RESULTS
Fourteen studies were included. The 33 codes that emerged from the inductive thematic analysis were grouped into three themes: 'The sense of danger and the terrifying aspect of death' (feeling in danger, surrounded by death, persecuted by people around, and feeling unsafe), 'The presence of someone or something nearby' (perceiving the loved ones, feeling overwhelmed by scary creatures, and being neglected by those around me), and 'The reality behind the world perceived by the senses' (travelling the world, stimulating the senses, feeling peaceful, and living in a fantasy world). The most frequent code in the studies was 'Be with a family member', with an intensity of 35.7%.
CONCLUSION
The patient's experience described as delusional is considered a real event by the person experiencing it. Further research is needed to investigate the extent to which these experiences lead to poorer early and late outcomes for patients, and to test strategies to prevent this.
IMPLICATIONS FOR CLINICAL PRACTICE
A deeper understanding of the phenomenon may help healthcare professionals to recognise precursors, symptoms and consequences of delusional memories and intervene with appropriate help. One strategy would be to further humanise care and focus on family involvement and communication with patients to overcome the factual events that can potentially alter patients' quality of life.
Topics: Adult; Humans; Quality of Life; Intensive Care Units; Patients; Emotions; Family; Qualitative Research
PubMed: 38176133
DOI: 10.1016/j.iccn.2023.103617 -
Cureus Nov 2023Diabetes mellitus (DM) is a chronic metabolic disorder characterized by elevated blood glucose levels, severity continues to rise worldwide. This systematic review seeks... (Review)
Review
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by elevated blood glucose levels, severity continues to rise worldwide. This systematic review seeks to examine the prevalence of diabetes and its associated comorbid conditions, aiming to provide insights into the multifaceted impact of diabetes on a broader scale. DM exhibits a positive correlation with advancing age, and it's strongly influenced by genetic predisposition. In recent years, there has been a discernible global increase in the prevalence of type 1 diabetes (T1D), as evidenced by extensive epidemiological studies. Individuals with DM frequently have a positive familial history, and the presence of DM in both parents or solely the mother significantly amplifies genetic susceptibility. Moreover, non-genetic factors, such as acute psychological stressors, obesity, pregnancy, and smoking play a pivotal role in the development of DM. Notably, urinary tract infections (UTIs) are a common comorbidity in patients with type 2 diabetes (T2D) and all patients with T1D. T2D is prevalent, particularly among females, and its incidence rises with age. UTIs are prevalent among individuals with diabetes, particularly females, with Escherichia coli (E. coli) isolates being the primary etiological agents responsible for UTI inflammation. Insulin resistance is a common feature in both prediabetes and prehypertension, serving as a precursor to these conditions. The increasing incidence of T2D in regions with high tuberculosis (TB) prevalence emphasizes the significance of understanding DM as a substantial TB risk factor. DM is associated with a threefold elevation in TB risk and a twofold increase in unfavorable outcomes during TB treatment. Notably, the global prevalence of DM has led to a larger population of TB patients with comorbid DM than TB patients coinfected with HIV. Diabetes and sepsis contribute significantly to worldwide morbidity and mortality, with diabetic individuals experiencing more post-sepsis complications and increased mortality. The coexistence of hypertension and T2D is a common comorbidity, with hypertension incidence being twice as high among individuals with diabetes compared to those without, often linked to insulin resistance and a heightened risk of diabetes onset.
PubMed: 38146555
DOI: 10.7759/cureus.49374 -
Cureus Oct 2023Barrett's esophagus (BE) remains a significant precursor to esophageal adenocarcinoma, requiring accurate and efficient diagnosis and management. The increasing... (Review)
Review
Barrett's esophagus (BE) remains a significant precursor to esophageal adenocarcinoma, requiring accurate and efficient diagnosis and management. The increasing application of machine learning (ML) technologies presents a transformative opportunity for diagnosing and treating BE. This systematic review evaluates the effectiveness and accuracy of machine learning technologies in BE diagnosis and management by conducting a comprehensive search across PubMed, Scopus, and Web of Science databases up to the year 2023. The studies were organized into five categories: computer-aided systems, natural language processing and text-based systems, deep learning on histology and biopsy images, real-time and video analysis, and miscellaneous studies. Results indicate high sensitivity and specificity across machine learning applications. Specifically, computer-aided systems showed sensitivities ranging from 84% to 100% and specificities from 64% to 90.7%. Natural language processing and text-based systems achieved an accuracy as high as 98.7%. Deep learning techniques applied to histology and biopsy images displayed sensitivities up to greater than 90% and a specificity of 100%. Furthermore, real-time and video analysis technologies demonstrated high performance with assessment speeds of up to 48 frames per second (fps) and a mean average precision of 75.3%. Overall, the reviewed literature underscores the growing capability and efficiency of machine learning technologies in diagnosing and managing Barrett's esophagus, often outperforming traditional diagnostic methods. These findings highlight the promising future role of machine learning in enhancing clinical practice and improving patient care for Barrett's esophagus.
PubMed: 38021699
DOI: 10.7759/cureus.47755