BACKGROUND:The rostral ventromedial medulla (RVM) is a brainstem structure that integrates descending modulatory signaling and contains neurons highly responsive to opioid receptor activation. Despite the well-established effects of opioids in the RVM, the neurochemical adaptations following sustained morphine exposure remain poorly understood. In particular, the contribution of G-protein-coupled inwardly rectifying potassium type 2 (GIRK2) channels, key mediators of opioid receptor-dependent antinociception has not been fully characterized. We hypothesized that GIRK2 channels are essential for morphine-induced metabolic alterations in the RVM. METHODS:In vivo proton nuclear magnetic resonance spectroscopy (1H NMR) was used to examine metabolite responses to prolonged morphine exposure. Metabolite profiles were compared between wild-type and GIRK2 heterozygous mutant (GIRK2+/-) mice before and after four days of subcutaneous implantation with placebo or morphine pellets. RESULTS:In wild-type mice, morphine exposure significantly increased levels of phosphocreatine, total creatine, glutamine, glutathione, taurine, and glycerophosphocholine plus phosphocholine (GPC + PCh), while decreasing N-acetylaspartate (NAA). These changes suggest enhanced energy storage, activation of antioxidant pathways, increased membrane turnover, and alterations in neuronal integrity and excitatory neurotransmission. In contrast, GIRK2+/- mice exhibited attenuated or opposite responses to morphine, characterized by elevated glutamate and reductions in glutamine, GPC + PCh, and total creatine, with no change in NAA. These differential responses indicate that GIRK2 channels influence neurochemical adaptations to morphine in the RVM. CONCLUSION:These findings identify the GIRK2 channel as an important modulator of morphine-induced metabolic changes in the RVM. The observed neurochemical alterations likely reflect adaptive responses to sustained opioid exposure.

Life history theory seeks to understand how organisms distribute energy between physiological functions across the life course. A central assumption is that energy allocation involves 'trade-offs' between competing functions relating to defence, maintenance, reproduction, and growth. Constraints on human energy expenditure may produce trade-offs during energetic stress, affecting functions critical for homeostasis, survival, and reproduction. While there is some evidence for binary trade-offs between two functions in humans, no studies have tested physiological resource prioritisation across multiple functions under energetic constraint. This study empirically assessed multiple human life history trade-offs and the proximate biological mechanisms underpinning them. We recruited 147 ultra-endurance athletes (107 male, 40 female) participating in four environmentally diverse multiday ultramarathons and one multiweek ocean rowing event. The severe energetic demands of these competitions provide a valuable opportunity to provoke and observe detectable trade-offs. We found evidence of trade-offs across multiple functions. Specifically, investment in defence (as indexed by immune biomarkers) was broadly prioritised relative to investment in storage, reproduction and maintenance. Our results enhance current understanding of the role of phenotypic plasticity in human adaptability and have implications for athlete health and performance as well as the emerging discipline of evolutionary public health.

Pulmonary hypertension (PH) is a progressive disease in which the pulmonary arteries thicken and narrow, raising pulmonary vascular resistance (PVR) and eventually straining the right ventricle. Known gene mutations explain only a minority of cases and often do not account for why the disease starts, worsens, or varies so widely between patients. Growing evidence suggests that epigenetic changes, chemical marks on DNA and its packaging that alter how genes are used without changing the DNA sequence, help explain this gap. These changes, including DNA methylation, histone modification, and non-coding RNAs, can be triggered by common exposures and disease states, and they can produce lasting shifts in vascular, immune, and metabolic pathways. This narrative review synthesizes current data showing how intrinsic stresses (mitochondrial dysfunction, oxidative stress, and cancer-like metabolic reprogramming) interact with extrinsic and often modifiable factors. Obesity, cigarette smoke, asbestos exposure, chronic hypoxia, and systemic inflammation drive PH through epigenetic reprogramming. We highlight major molecular hubs implicated across studies, including bone morphogenetic factor receptor 2 (BMPR2), NOTCH3, endothelin-1 (ET-1), transforming growth factor‑β (TGF-β), interleukin‑6 (IL-6), and CCL5, and we summarize emerging therapeutic approaches aimed at epigenetic regulators and microRNA networks. This narrative review was not conducted under Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and does not constitute a formal systematic review. The information in this review provides a practical framework for clinicians and researchers to improve risk assessments, to employ biomarkers, and to develop therapies that go beyond vasodilation to address upstream drivers of pulmonary arterial remodeling. This framework may also serve as a model for other difficult-to-treat diseases in which incomplete genetic explanations and limited attention to environmental exposures have slowed progress in prevention, early detection, and personalized treatment.

Abstract:N‑acetylcysteine (NAC), a thiol‑containing acetylated derivative of L‑cysteine, has emerged as a multifunctional therapeutic agent beyond its classic role as a mucolytic and as an antidote for acetaminophen toxicity. As a glutathione precursor and direct free‑radical scavenger, NAC exhibits dual antioxidant and anti‑inflammatory effects, modulating key pathways such as Nrf2 and NF‑κB and influencing cellular redox homeostasis. This comprehensive review synthesizes preclinical and clinical evidence for NAC's effects across multiple organ systems. In the respiratory system, NAC improves mucus clearance, reduces exacerbations in COPD, and shows variable benefits in idiopathic pulmonary fibrosis, with emerging precision‑medicine approaches exploring genotype‑guided therapy. In cardiovascular settings, NAC demonstrates endothelial‑protective properties, enhanced nitric oxide bioavailability, and potential to reduce perioperative oxidative injury, though large‑scale trials report mixed impacts on mortality and arrhythmia rates. Renal studies reveal protective effects against contrast‑induced nephropathy and perioperative acute kidney injury by attenuating oxidative and inflammatory markers. Within the central nervous system, NAC has shown neuroprotective properties in vitro and in vivo, including reduced oxidative stress, modulated glutamate transport, and partial mitigation of neurodegenerative processes, although clinical results remain inconsistent. Its safety profile is generally favorable, with mild gastrointestinal effects being the most common adverse events. Collectively, these findings highlight NAC as a promising adjunctive therapy with broad biological plausibility. However, variability in dosing, bioavailability, and patient selection underscores the need for further mechanistic research and well‑designed randomized trials to establish its long‑term clinical utility.

Introduction:Artificial intelligence (AI) is revolutionizing neurosurgery by enhancing diagnostic precision, surgical planning, and postoperative management. However, its integration raises ethical concerns related to bias, privacy, accountability, and the potential dehumanization of healthcare. This review focuses on navigating these challenges while maximizing AI's potential in improving patient care. Methodology:A narrative review was conducted by identifying studies from PubMed, Cochrane Library, and Google Scholar databases. The search utilized the following keywords: "artificial intelligence," "neurosurgery," "machine learning," "data privacy," "robotic surgery," "ethics," and "bias." The review primarily focused on issues of dataset bias, data privacy, and the need for transparency and accountability in clinical decision-making. Results and critical insights:AI significantly improves diagnostic accuracy and the management of neurological conditions; however, it also poses risks, such as exacerbating healthcare disparities and compromising patient data security. Recommended strategies include the development of ethical frameworks, inclusion of diverse datasets, and fostering surgeon-AI collaboration to ensure equitable outcomes. Conclusion:AI holds immense promise in enhancing neurosurgical diagnostics, surgical planning, and postoperative care. Nonetheless, its responsible integration demands robust ethical and regulatory frameworks that prioritize patient safety, transparency, and equity. Interdisciplinary collaboration and continuous real-world validation remain essential to address ongoing clinical and ethical challenges as AI technologies evolve.

Introduction:Artificial intelligence (AI) is revolutionizing cardiology by enhancing diagnostic precision, prognostic accuracy, and treatment planning. Its integration raises ethical concerns like bias, privacy, accountability, and the risk of dehumanizing healthcare. This review focuses on navigating these challenges while maximizing AI's potential in patient care. Methodology and aims:A narrative review was conducted to explore the ethical challenges associated with AI in cardiology. Key areas of focus included bias in training datasets, data privacy, the "black-box" nature of AI systems, and the need for transparency and accountability in clinical decision-making. Results and critical insights:AI improves accuracy in diagnosing and managing cardiovascular conditions but presents risks such as exacerbating healthcare disparities and challenges in patient data security. Strategies include creating ethical frameworks, integrating diverse datasets, and emphasizing the importance of clinician-AI collaboration to ensure equitable outcomes. Conclusion and limitations:AI offers transformative opportunities for cardiology, yet its success hinges on addressing ethical, technical, and regulatory challenges. Robust frameworks promoting fairness, transparency, and privacy are crucial. Limitations include a lack of real-world validation and the need for ongoing oversight to adapt to evolving clinical demands.

RATIONALE:Adaptive deep brain stimulation (aDBS) represents a notable advancement in treating Parkinson's disease (PD), as it offers enhanced therapeutic outcomes and personalized management by adjusting stimulation parameters in real-time according to individual neural signals. This approach minimizes adverse effects commonly associated with standard continuous deep brain stimulation (cDBS). This case report describes the progress of a 62-year-old man with severe PD who demonstrated notable enhancement in motor symptoms and quality of life throughout a 3-month trial period using aDBS. PATIENT CONCERNS:A 62-year-old man who has been suffering from Parkinson's disease. DIAGNOSES:The patient had been diagnosed with PD for 10 years. The patient's motor symptoms, including dyskinesia during the on-state and akinesia during the off-state, progressively worsened over time. INTERVENTIONS:The patient underwent bilateral subthalamic nuclei DBS surgery with cDBS. Following progressive worsening of motor symptoms, he was transitioned to aDBS. OUTCOMES:The aDBS system adaptively modified stimulation parameters by utilizing real-time neural feedback from beta band activity detected in the subthalamic nucleus, resulting in decreased dyskinesia and reduced reliance on medication. The customized strategy led to a significant improvement in motor symptoms, a reduction in dyskinesia, and an overall enhancement in quality of life during the 3-month trial period. LESSONS:Existing evidence highlights the ability of aDBS to improve motor control and reduce problems associated with DBS, such as speech and gait abnormalities. Research findings have demonstrated significant improvements in motor scores and a reduction in stimulation time, highlighting the effectiveness of aDBS and its ability to prolong the lifespan of devices.

Respiratory depression is the leading cause of death in opioid overdose and is closely associated with the development of tolerance following repeated morphine use. However, the neurochemical adaptations in brainstem regions that regulate breathing, particularly under chronic opioid exposure, remain poorly understood. G-protein-gated inwardly rectifying potassium (GIRK) channels, especially the GIRK2 subunit, are expressed in rhythm-generating neurons of the pre-Bötzinger complex and have been implicated in opioid-induced respiratory depression. Nonetheless, their specific role in morphine-induced neurochemical changes is not yet fully defined. In this study, in vivo proton magnetic resonance spectroscopy (1H MRS) was used in mice to assess morphine-induced metabolite changes in ventral brainstem regions encompassing the pre-Bötzinger complex. Wild-type mice were compared with GIRK2 heterozygous (GIRK2+/-) mutants. Baseline levels of several metabolites including glutamate (Glu), myo-inositol (Ins), N-acetylaspartate plus N-acetylaspartylglutamate (NAA + NAAG), and glutamate plus glutamine (Glu + Gln) differed significantly between GIRK2+/- and wild-type mice. Despite these baseline differences, many of morphine's effects on metabolite levels were similar in the wild-type and GIRK2+/- mice. Morphine increased phosphocreatine (PCr) in both genotypes, while total creatine (Cr + PCr) decreased only in the wild-type mice. Glutamine levels increased significantly in both groups. Notably, NAA decreased in wild-type but increased in GIRK2+/- mice, whereas NAA + NAAG decreased in both. These findings demonstrate that chronic morphine exposure induces substantial neurochemical changes in brainstem respiratory centers. Although the GIRK2+/ - mutation altered some of the metabolite responses, it does not fully block morphine's effects, highlighting the complexity of opioid-induced adaptations in the respiratory control networks.

Background Cognitive load theory postulates that effective learning depends on balancing a learner's cognitive capacity with cognitive load. Medical students are required to answer complex multiple-choice questions (MCQs) that involve complex vignettes and distractors, in 90 s per question. This demands the ability to rapidly process information, filter out irrelevant data, and suppress incorrect yet tempting answer choices. The Stroop color-conflict test represents a cognitive interference task that may simulate time-limited conditions for answering MCQs. This exploratory study tested whether selected quantitative electroencephalographic (qEEG) indices could behave as biomarkers that remain stable across sequential Stroop loads. Methods Thirteen healthy adults (11 retained after outlier removal) completed a midline (Fz, Cz, Pz) qEEG protocol comprising (i) 5 minutes of resting baseline, (ii) 5 minutes after a congruent low-load (LL) Stroop test and (iii) 5 minutes after an incongruent high-load (HL) Stroop test. Voltage amplitude (µV) and mode frequency (Hz) were extracted for theta (4-7 Hz), alpha (8-12 Hz), low-beta (12-20 Hz) and high-beta (20-30 Hz) bandwidths. Derived ratios, θ/β, α/β, θ/α and high-β/low-β, plus a frontal-posterior theta ratio (Fz/Pz), were analyzed with paired t-tests and repeated-measures ANOVA. Outliers were removed using a strict |z| > 2 threshold applied to every site-specific metric. Results Significant Baseline → LL load sensitivity was found for alpha-dominant (mode) frequency. The dominant frequencies, voltage amplitudes and voltage amplitude ratios for the other bandwidths (θ, low-β, high-β) were nonsignificant and therefore not load sensitive. None of the markers exhibited significant changes from LL → HL. Alpha voltage amplitudes were found to be higher at Pz than at Cz and Fz, exhibiting posterior dominant site sensitivity. High-β/low-β and θ/β ratios were found to be higher at Fz and Cz than at Pz, exhibiting frontal dominant site sensitivity. Conclusion These findings suggest significant Stroop testing-related qEEG changes in medical students trained to answer complex MCQs under time constraints. Alpha dominant frequency was found to be load sensitive but site insensitive. Load insensitivity of alpha voltage amplitude, θ/β ratio and high-β/low-β ratio at the Cz, Fz and Pz midline recording sites suggests site specificity of these variables. These findings appear to support the hypothesis that the site-specific topographic markers alpha voltage amplitude, θ/β and high-β/low-β ratio may be useful for characterizing responses to Stroop testing. However, the load sensitivity of alpha dominant frequency measured at the Cz, Fz and Pz midline recording sites may be useful for workload tracking to identify and remediate information-processing problems. These preliminary findings should be interpreted cautiously pending larger studies of cognitive loading in other populations of learners trained to take high-stakes, time-limited examinations.

[This corrects the article DOI: 10.7759/cureus.84059.].

Background: Lung cancer, a significant global health challenge, notably the non-small-cell lung cancer (NSCLC) subtype, is a topic of utmost importance. The continuous advancements in NSCLC treatment, especially in the context of anaplastic lymphoma kinase (ALK)-positive NSCLC, are of great interest. A thorough review of alectinib’s comparative efficacy and safety with other treatment modalities is a crucial step, and the role of clinicians and surgeons is integral in optimizing patient care. This review can also inform neoadjuvant therapies and enhance surgical education, facilitating more informed decision-making processes between surgeons and patients. Methods: This comprehensive systematic review results from rigorous screening. Following a rigorous screening process of the PubMed, PubMed Central, and Medline databases by quality assessment and application of inclusion/exclusion criteria filters, 9 relevant articles were identified that directly addressed the research question and provided a holistic understanding of it. The analysis included a total of 1403 patients from 9 different studies. Alectinib was given to 836 patients, while 567 patients received other chemotherapeutic drugs. The primary objective of this study was to evaluate and compare the efficacy of alectinib with other treatment modalities. Results: The analysis revealed that alectinib is promising for ALK-positive NSCLC cases, with significantly better efficacy and a positive impact on limiting central nervous system metastases. Alectinib’s favorable safety profile, with medically manageable adverse events, provides reassurance about its safety compared with other treatment modalities. Conclusions: Alectinib has emerged as a viable, significantly superior treatment option for patients with ALK-positive NSCLC. The superior efficacy and manageable safety profile are significant; it remains a novel therapy with much potential, such as neoadjuvant therapy, which will make significant strides in patient care of ALK-positive NSCLC. Therefore, it is crucial for healthcare professionals, including surgeons, to be well-versed in alectinib and its potential. This knowledge will empower them and instill confidence in their ability to provide the best care for their patients.

INTRODUCTION:It is well known that opiate addiction is a neurobiological disease associated with dysregulation of multiple neurotransmitters and neurochemicals. Previous ex-vivo 1H nuclear magnetic resonance (NMR) studies have yielded mixed findings concerning opiate-induced neurometabolic changes at key reward-addiction sites. Whether such changes reflect the conditions in a live animal remains unknown. The present study was therefore designed to fill this knowledge gap by determining the effects of morphine-induced neurometabolic changes under in-vivo conditions. METHODS:In-vivo 1H NMR spectroscopy (SA Instruments, Stony Brook, NY) was used to measure neurochemical changes in nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) of mice, subjected to twice-daily injections of morphine (10 mg kg-1 s.c.) for five days. RESULTS:Morphine induced significant changes in the concentrations of a number of metabolites in both mPFC and NAc. The glutamine component of the glutamine-glutamate-GABA excitatory-inhibitory cycle, increased in both mPFC and NAc. Significant increase in glutamate was also observed at mPFC, but not in NAc. The phosphocreatine, marker for energy metabolism, and the N-acetylaspartate marker for neuronal viability and energy metabolism decreased significantly in both mPFC and NAc. Glycerophosphocholine + phosphocholine, markers for cell membrane integrity, increased significantly in both NAc and mPFC after morphine. The antioxidant neurometabolites taurine and glutathione increased significantly in NAc; however, taurine decreased, and glutathione was unchanged in mPFC after morphine. Inositol, a marker for neuroinflammation, increased significantly in NAc. CONCLUSION:The present study is the first in-vivo 1H NMR spectroscopy in mice to demonstrate morphine-induced dysregulation of multiple metabolites and neurochemicals within the reward-addiction neurocircuitry.

INTRODUCTION:This pilot study was designed to test the hypothesis that quantitative electroencephalographic (qEEG) measurements reflect physiological adaptations for brain energy reallocation. The study focused on a team of three well-matched male rowers participating in a 30-day, 2,650-mile continuous transatlantic rowing competition, examining the effects of extreme, prolonged stress on brain function and metabolic adaptations. METHODS:Measurements at the start and finish lines included body weight, height, waist circumference, body fat, and a panel of hormones and biochemical markers. Post-race qEEG parameters were recorded under eyes-open (EO) and eyes-closed (EC) conditions. qEEG data were compared to a reference population (ages 6-90 years) and to an age-matched 27-year-old male medical student serving as a control subject. qEEG analysis evaluated voltage amplitudes, wave distribution patterns, theta-to-beta ratios (TBR), and coherence levels. Hormonal changes and oxidative stress markers were also assessed before and after race. RESULTS:Two rowers exhibited post-race dominance of high-frequency beta activity, while one displayed co-dominance of delta and beta waves. Compared to the control subject (TBR = 1.25), the rowers' low TBRs (< 0.2) indicated high vigilance and low relaxation during EC conditions. Cortisol levels increased in all rowers and were associated with beta coherence >1 SD above the reference mean. Testosterone decreased in two rowers but increased in one; the smallest cortisol increase corresponded with the largest testosterone decrement. Decreases in oxidative stress markers correlated with a shift from right- to left-sided alpha asymmetry, consistent with redistribution of alpha wave energy to the nondominant hemisphere. This pattern was also observed in the control subject. Increased testosterone in one rower was linked to a decrease in the percentage of sites exhibiting normal theta frequencies, indicating a potential role for testosterone in brain energy reallocation. CONCLUSION:The findings suggest that qEEG measurements reflect physiological adaptations in response to extreme stress, supporting the hypothesis that metabolic energy is reallocated to optimize vigilance and performance. The observed correlations between hormonal changes, oxidative stress markers, and qEEG parameters provide preliminary evidence of mechanisms for brain energy reallocation. These insights highlight the potential for qEEG to identify biomarkers of stress adaptation and lay the groundwork for larger studies to further elucidate these mechanisms.

Cold agglutinins are autoantibodies that can cause agglutination or clumping of red blood cells (RBCs) at temperatures below normal body temperature. This case report discusses a 37-year-old male patient who suffered from multiple injuries due to a motorcycle accident. The patient’s laboratory tests revealed a high level of cold agglutinins, which resulted in abnormal RBC parameters. The study aims to investigate the impact of cold agglutinins on RBC parameters in a trauma patient. The findings of this case report highlight the importance of recognizing cold agglutinins in trauma patients to avoid misinterpretation of laboratory results.

Previous studies have shown that right-sided frontal alpha asymmetry (fAA) is an electroencephalography (EEG) marker for negatively valenced emotions and a marker for negative self-perceptions of a person's psychosocial interactions. Alpha activity is affected by the changes in visual stimulation associated with eye-opening and eye-closing; theta activity is not so affected. Therefore, this analysis investigates the relationship between an individual's theta asymmetry and self-perceptions of their psychosocial interactions. We used quantitative electroencephalographic (qEEG) data from eight right-handed male medical students aged between 19 and 38 years, recorded under eyes-open (EO) and eyes-closed (EC) conditions. Significant correlations were found between self-reported measures of psychosocial interactions via the Interactive Self-Report Inventory (ISI). The main finding was that greater left-sided frontal temporal asymmetry (fTA) under both EO and EC conditions was associated with lower "regulated" ISI scores and lower "dependent" ISI scores. Greater left-sided temporal theta asymmetry (tTA), under EC conditions, was associated with higher "anxious" ISI scores. Greater left-sided prefrontal theta symmetry (pfTA), under EO conditions, was associated with lower "relaxed" ISI scores. These findings suggest that theta asymmetries in the frontal, prefrontal, and temporal cortices may be indicative of negative emotional states. The results of this study underscore the potential of pfTA, fTA, and tTA to be used as biomarkers for cognitive-emotional balance. The implications for mental health interventions, particularly personalized therapeutic approaches, are significant.

Wearable technology, including devices like Apple and Samsung watches, Fitbits, and smart rings, has become widely popular. However, while these consumer electronics are readily available, they do not yet meet the accuracy and safety standards required for medical devices by the U.S. Food and Drug Administration (FDA). The COVID-19 pandemic has spurred demand for wearable medical devices, particularly those that can support telemedicine and telehealth. Among these, wearable electronic stethoscopes hold significant promise for early detection and prevention of cardiovascular diseases, which remain the leading cause of death globally. This review highlights the potential of wearable electronic stethoscopes to transform cardiovascular health management by enabling early diagnosis and self-monitoring. Additionally, it examines the current challenges and technological advancements needed to overcome them, underscoring the vital role that wearable electronic stethoscopes could play in improving global health outcomes.

Systemic hypertension (HTN) is the hallmark of cardiovascular disease and the forerunner of heart failure. These associations have been established over decades of research on essential HTN. Advancements in the treatment of patients diagnosed with HTN, consisting of alpha- or beta-adrenergic receptor blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, thiazide, or aldosterone receptor blockers known as anti-mineralocorticoids, in the presence or absence of low sodium salt diets, often fail to control blood pressure adequately to prevent morbidity and mortality. Low sodium diets have had limited success in controlling HTN because low sodium intake is associated with renin-angiotensin-aldosterone system upregulation. Therefore, upregulating aldosterone secretion, sodium, and water retention which, in turn, moves the blood pressure back toward the range of HTN dictated by the baroreceptor reset value, as a compensatory mechanism, especially in resistant HTN. These impediments to blood pressure control in HTN may have been effectively circumvented by the advent of a new class of drugs known as aldosterone synthase inhibitors, represented by baxdrostat. The mechanism of action of baxdrostat as an aldosterone synthase inhibitor demonstrates the inextricable linkage between sodium and blood pressure regulation. Theoretically, combining a low sodium diet with the activity of this aldosterone synthesis inhibitor should alleviate the adverse effect of renin-angiotensin-aldosterone system upregulation. Aldosterone synthesis inhibition should also decrease the oxidative stress and endothelial dysfunction associated with HTN, causing more endothelial nitric oxide synthesis, release, and vasorelaxation. To the best of our knowledge, this is the first systematic review to summarize evidence-based articles relevant to the use of a novel drug (aldosterone synthase inhibitor) in the treatment of HTN and cardiovascular disease. Making the current database of relevant information on baxdrostat and other aldosterone synthase inhibitors readily available will, no doubt, aid physicians and other medical practitioners in their decision-making about employing aldosterone synthase inhibitors in the treatment of patients.

Now recognized as more than just the result of overeating or the consumption of poor-quality foods, obesity is understood to be a multifactorial disease, strongly correlated with a variety of environment-gene interactions. In addressing the complex public health issue of obesity, medical practitioners, along with their allied healthcare counterparts, face the challenge of reducing its prevalence by utilizing and sharing with patients the current, yet incomplete, scientific knowledge concerning the disease. While continued research is required to strengthen direct cause-effect relationships, substantial evidence links post-translational modifications such as DNA methylation and histone modifications of several candidate “obesity” genes to the predilection for obesity. Additional evidence supports the influence of maternal diet during the gestational period, individual diet, and other lifestyle and genetic factors in obesity. The purpose of this review is to synthesize the current information concerning epigenetic modifications that appear to support, or result from, the development of obesity. Such mechanisms may serve as therapeutic targets for developing novel prevention and/or treatment strategies for obesity or as epigenetic biomarkers for monitoring recovery.

Guillain-Barre syndrome (GBS), an immune-mediated disease of the peripheral nervous system, is mainly characterized by rapidly progressive ascending weakness of the limbs with reduced or absent deep tendon reflexes. The exact cause of GBS is unknown, but it often occurs after a gastrointestinal or respiratory infection. The present study represents a case of GBS in which multiple antecedent antigenic stimuli may have contributed to the development of GBS. The patient, a 28-year-old immunocompetent man with no significant medical history, presented to the emergency department (ED) with acute ascending flaccid paralysis that persisted for a few days. His initial symptoms included tingling in his legs, which started at his shin and calf and developed into numbness, which extended to his upper limbs and arms. A CT scan of the lumbar and cervical spine indicated minor L4 -L5 and L5-S1 disc herniation as well as slight bulging in C5-C6 and C7. The patient was discharged but returned to the ED for urgent treatment the next day after he weakened rapidly, losing the ability to walk or maintain balance. Based on his clinical presentation of ascending weakness and generalized hyporeflexia, he was diagnosed with GBS. Abnormal liver function and positive blood tests for anti-cytomegalovirus (anti-CMV) and anti-Epstein-Barr virus (anti-EBV) IgG and IgM antibodies diagnosed hepatitis, CMV, and EBV, respectively. The patient was treated with intravenous immunoglobulin therapy (IVIG; 27 g/day) and antiviral medicine (ganciclovir; 340 mg IV/day) for five days. His nonexistent deep tendon reflexes began to improve two to three days following treatment. He was able to ambulate longer distances with a walker, and his upper extremities regained full strength. This case highlights the importance of a multiple-treatment approach to the treatment of GBS, wherein multiple antigenic triggering factors may be involved.

Orthostatic hypotension (OH) is one of the most common autonomic dysfunctions, with high prevalence in populations of elderly, hypertensive, diabetic, or Parkinson's patients. Evidence is emerging that OH co-occurs with postprandial hypotension (PPH); a greater prevalence of PPH than of OH is reported for Parkinson's disease patients. OH is diagnosed by measuring the blood pressure changes associated with postural changes and often produces alterations in consciousness or other such bothersome symptoms as fainting. PPH is diagnosed by measuring the blood pressure changes associated with ingesting high carbohydrate test meals. Because of the time lag between food ingestion and absorption, PPH is often not reported as symptomatic and, therefore, not diagnosed as PPH. OH and PPH are independent predictors for all causes of mortality. Relative underdiagnosis may qualify PPH as a "silent killer" disease. This review is aimed at providing updates on the epidemiology, pathophysiology, and clinical aspects associated with the diagnosis and treatment of PPH. Highlighting the current gaps in knowledge and research about PPH is expected to make medical practitioners more cognizant of the dangers of underdiagnosis and motivate future research to identify individuals and populations at high risk for PPH and its sequelae.