Rapid and Chronic Ethanol Tolerance Are Composed of Distinct Memory-Like States in Drosophila.

Ethanol tolerance is the first type of behavioral plasticity and neural plasticity that is induced by ethanol intake, and yet its molecular and circuit bases remain largely unexplored. Here, we characterize the following three distinct forms of ethanol tolerance in male Drosophila: rapid, chronic, and repeated. Rapid tolerance is composed of two short-lived memory-like states, one that is labile and one that is consolidated. Chronic tolerance, induced by continuous exposure, lasts for 2 d, induces ethanol preference, and hinders the development of rapid tolerance through the activity of histone deacetylases (HDACs). Unlike rapid tolerance, chronic tolerance is independent of the immediate early gene Hr38/Nr4a Chronic tolerance is suppressed by the sirtuin HDAC Sirt1, whereas rapid tolerance is enhanced by Sirt1 Moreover, rapid and chronic tolerance map to anatomically distinct regions of the mushroom body learning and memory centers. Chronic tolerance, like long-term memory, is dependent on new protein synthesis and it induces the kayak/c-fos immediate early gene, but it depends on CREB signaling outside the mushroom bodies, and it does not require the Radish GTPase. Thus, chronic ethanol exposure creates an ethanol-specific memory-like state that is molecularly and anatomically different from other forms of ethanol tolerance.SIGNIFICANCE STATEMENT The pattern and concentration of initial ethanol exposure causes operationally distinct types of ethanol tolerance to form. We identify separate molecular and neural circuit mechanisms for two forms of ethanol tolerance, rapid and chronic. We also discover that chronic tolerance forms an ethanol-specific long-term memory-like state that localizes to learning and memory circuits, but it is different from appetitive and aversive long-term memories. By contrast, rapid tolerance is composed of labile and consolidated short-term memory-like states. The multiple forms of ethanol memory-like states are genetically tractable for understanding how initial forms of ethanol-induced neural plasticity form a substrate for the longer-term brain changes associated with alcohol use disorder.

Sir2/Sirt1 Links Acute Inebriation to Presynaptic Changes and the Development of Alcohol Tolerance, Preference, and Reward.

UNLABELLED: Acute ethanol inebriation causes neuroadaptive changes in behavior that favor increased intake. Ethanol-induced alterations in gene expression, through epigenetic and other means, are likely to change cellular and neural circuit function. Ethanol markedly changes histone acetylation, and the sirtuin Sir2/SIRT1 that deacetylates histones and transcription factors is essential for the rewarding effects of long-term drug use. The molecular transformations leading from short-term to long-term ethanol responses mostly remain to be discovered. We find that Sir2 in the mushroom bodies of the fruit fly Drosophila promotes short-term ethanol-induced behavioral plasticity by allowing changes in the expression of presynaptic molecules. Acute inebriation strongly reduces Sir2 levels and increases histone H3 acetylation in the brain. Flies lacking Sir2 globally, in the adult nervous system, or specifically in the mushroom body α/ß-lobes show reduced ethanol sensitivity and tolerance. Sir2-dependent ethanol reward is also localized to the mushroom bodies, and Sir2 mutants prefer ethanol even without a priming ethanol pre-exposure. Transcriptomic analysis reveals that specific presynaptic molecules, including the synaptic vesicle pool regulator Synapsin, depend on Sir2 to be regulated by ethanol. Synapsin is required for ethanol sensitivity and tolerance. We propose that the regulation of Sir2/SIRT1 by acute inebriation forms part of a transcriptional program in mushroom body neurons to alter presynaptic properties and neural responses to favor the development of ethanol tolerance, preference, and reward. SIGNIFICANCE STATEMENT: We identify a mechanism by which acute ethanol inebriation leads to changes in nervous system function that may be an important basis for increasing ethanol intake and addiction liability. The findings are significant because they identify ethanol-driven transcriptional events that target presynaptic properties and direct behavioral plasticity. They also demonstrate that multiple forms of ethanol behavioral plasticity that are relevant to alcoholism are initiated by a shared mechanism. Finally, they link these events to the Drosophila brain region that associates context with innate approach and avoidance responses to code for reward and other higher-order behavior, similar in aspects to the role of the vertebrate mesolimbic system.

From confusion to clarity: a case report of hypertensive and autoimmune encephalopathy in an elderly woman.

Introduction and importance: Hypertensive encephalopathy is a critical condition characterized by acute hypertension-induced cerebral dysfunction, while autoimmune encephalitis involves immune-mediated neuronal damage. Distinguishing between these entities is crucial due to overlapping clinical features and distinct management approaches. Case presentation: The authors present a case of a 70-year-old woman with poorly controlled hypertension who initially presented with confusion and severe headache. Despite treatment for a hypertensive emergency, including intravenous labetalol, her neurological status deteriorated. She developed seizures and fever, prompting further investigations. Initial imaging and cerebrospinal fluid (CSF) analysis suggested hypertensive encephalopathy, but negative microbiological findings and persistent symptoms necessitated consideration of autoimmune causes. Clinical discussion: Clinical evaluation, EEG findings, and autoimmune panels were pivotal in diagnosing autoimmune encephalitis, supported by positive anti-NMDA receptor antibodies. Prompt initiation of high-dose intravenous immunoglobulin (IVIG) led to clinical improvement, underscoring the role of targeted immunotherapy. Conclusion: This case highlights the diagnostic complexities and therapeutic challenges of hypertensive and autoimmune encephalopathy overlap in elderly patients. Early recognition and tailored immunotherapy were instrumental in achieving favorable outcomes, advocating for a multidisciplinary approach to managing such complex neurological conditions.

Addressing complexities in ß-thalassemia care: a case series from a resource-limited setting.

Introduction and importance: ß-thalassemia is a hereditary blood disorder with a global prevalence, presenting diagnostic and management challenges, particularly in regions with high consanguinity rates. Diagnostic methods include clinical assessments, genetic testing, and hemoglobin electrophoresis. Treatment typically involves transfusions and chelation therapy, with gene therapy showing promise. This case series emphasizes the need for tailored care strategies and global health initiatives to improve outcomes for ß-thalassemia patients worldwide. Methods: This case series involves five patients from rural Nepal presenting various ß-thalassemia manifestations. The cases highlight the challenges in diagnosis and management in resource-limited settings. Data were collected through clinical assessments, laboratory investigations, and follow-ups. Each patient's medical history, presentation, and treatment regimen were documented. Outcomes: The cases underscore the importance of regular follow-ups, community engagement, and personalized treatment strategies tailored to genetic profiles. Key findings include the necessity for consistent transfusion schedules, iron overload monitoring, and managing complications associated with ß-thalassemia. Enhanced education and healthcare collaboration were noted as critical for optimizing care and outcomes in resource-limited settings. Conclusions: Managing ß-thalassemia in resource-limited settings demands timely intervention, regular monitoring, and community involvement. Enhanced healthcare collaboration, access to advanced diagnostic tools, and tailored treatment strategies are paramount in addressing the unique challenges of ß-thalassemia. These measures are essential for ensuring an improved quality of life for affected individuals in such regions.

Etiology and epidemiology of acute exacerbations of chronic obstructive pulmonary disease in Eastern Nepal: a narrative review.

This narrative review aims to examine the etiology and epidemiology of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in Eastern Nepal. A systematic search was conducted to identify relevant studies published in English, focusing on combinations of keywords such as "acute exacerbation of chronic obstructive pulmonary disease," "AECOPD," "Nepal," "etiology," "epidemiology," "environmental exposure," "comorbidities," and "socioeconomic factors." Synthesizing findings from recent studies, it highlights the multifactorial nature of AECOPD, including the roles of respiratory infections, environmental exposures, and comorbidities. Key findings indicate that respiratory infections (both viral and bacterial) and non-infectious factors such as air pollution and biomass fuel combustion significantly contribute to AECOPD. Socio-economic factors, particularly among women using traditional biomass fuels and engaged in smoking, also play a critical role. The review emphasizes the need for targeted interventions and preventive strategies to manage AECOPD effectively in this region. Conclusions suggest that understanding local patterns of AECOPD etiology is crucial for developing region-specific interventions to reduce exposure to risk factors and manage comorbidities, thereby improving clinical outcomes and reducing healthcare utilization.

Fatal aconite poisoning in a rural Nepali traditional healer: clinical challenges and management strategies.

Introduction and importance: Aconite, also known as Aconitum spp., is a group of highly toxic flowering plants used historically in traditional medicine despite their potent neurotoxic and cardiotoxic effects. In rural Nepal, where traditional healing practices are prevalent, accidental ingestion of Aconite remains a significant public health concern due to its resemblance to medicinal herbs. Case presentation: The authors present a case of severe Aconite poisoning in a 45-year-old male traditional healer from rural Nepal. Following ingestion of a homemade herbal tea containing Aconitum species, the patient developed rapid-onset symptoms, including paresthesia around the mouth, severe abdominal pain, and progressive weakness. Upon admission, he exhibited signs of cardiovascular compromise and metabolic acidosis. Despite aggressive management, including gastric lavage, fluid resuscitation, and symptomatic treatment, the patient succumbed to cardiovascular collapse within 12 h of admission. Clinical discussion: Aconite poisoning manifests with early neurological symptoms and progresses to severe gastrointestinal and cardiovascular complications. Its toxicity is attributed to aconitine, which disrupts cellular function by binding to voltage-gated sodium channels. Management focuses on supportive care and symptomatic treatment, given the absence of a specific antidote and challenges in rural healthcare settings. Conclusion: This case underscores the critical need for awareness among healthcare providers and the public regarding the dangers of Aconite. Improved education, healthcare infrastructure, and early intervention are essential in mitigating the morbidity and mortality associated with Aconite poisoning in resource-limited settings.

Radiological diagnosis and emergency endovascular management, and follow-up of a unruptured right subclavian artery aneurysm in an elderly patient: A case report.

Right subclavian artery aneurysms are rare vascular anomalies that can present significant diagnostic and management challenges, especially in elderly patients. We present a case of a 72-year-old female who presented with sudden onset chest pain and was diagnosed with an unruptured right subclavian artery aneurysm with partial thrombus formation. Advanced imaging, including chest X-ray and contrast-enhanced CT scan, confirmed the diagnosis and guided a successful endovascular repair, stabilizing the patient. Follow-up care included regular clinical assessments and imaging studies to monitor the aneurysm's status and detect potential complications. This case underscores the critical role of early radiological diagnosis and prompt intervention in managing subclavian artery aneurysms, highlighting the effectiveness of endovascular techniques in such cases.

Managing neurofibromatosis type I and vision impairment in a resource-limited setting: a case study and multidisciplinary approach.

Background: Neurofibromatosis type I (NF1) is a genetic disorder characterized by the development of multiple benign tumors along nerves in the skin, brain, and other parts of the body. It is associated with a range of clinical manifestations, including skin lesions, neurofibromas, and ocular abnormalities, which can significantly impact a patient's quality of life. Management of NF1 is particularly challenging in resource-limited settings due to limited access to diagnostic and therapeutic resources. Clinical presentation: A 62-year-old woman with a known history of NF1 presented with progressive visual impairment. Her condition began in childhood with multiple hyperpigmented skin macules, which developed into numerous cutaneous tumors over time. Examination revealed numerous neurofibromas, café-au-lait spots, and axillary freckling. Significant visual impairment was caused by large fibromas on her eyelids. Histological analysis confirmed benign nerve tissue tumors. Clinical discussion: The management strategy in this resource-limited setting focused on regular monitoring, patient education, symptomatic treatment, and multidisciplinary care. Despite the limitations, the patient's condition was managed effectively through these adapted strategies. The importance of genetic testing for confirmation and further management was noted but not performed due to resource constraints. Conclusion: This case highlights the complexities of managing NF1 in resource-limited settings, emphasizing the need for adaptable management approaches. Multidisciplinary care and patient education were crucial in improving the patient's quality of life. This case underscores the importance of early diagnosis and intervention to prevent complications like visual impairment.

Challenges in diagnosing and managing hyper-IgE syndrome in a resource-limited setting: a case report.

Introduction and importance: Hyper-IgE syndrome (HIES), also known as Job syndrome, is a rare immunodeficiency disorder characterized by elevated immunoglobulin E levels and recurrent infections. Diagnosing and managing HIES in resource-limited settings is challenging due to the lack of advanced diagnostic tools. This report highlights the necessity of clinical evaluation and basic laboratory investigations for diagnosing HIES. Case presentation: A 3-year-old male presented with fever, cough, and widespread pustular lesions. He had a history of recurrent respiratory infections and otitis media. Physical examination revealed characteristic facial features, skin findings, and laboratory investigations showed elevated immunoglobulin E levels (>3000 IU/ml) and leukocytosis. A clinical diagnosis of HIES was made, and the patient responded well to antibiotics, antihistamines, and topical steroids. Clinical discussion: HIES is caused by genetic mutations affecting immune function, primarily involving STAT3 and DOCK8 genes. Diagnosis in resource-limited settings relies on clinical features and basic investigations. Challenges include the unavailability of genetic testing. Management includes antibiotics and symptomatic relief adapted to available resources. Conclusion: Diagnosing and managing HIES in resource-limited settings requires adaptation of clinical approaches to available resources. This case underscores the importance of clinical vigilance and basic diagnostic tools in diagnosing rare immunodeficiencies.

Morphometric study of normal acetabulum on computed tomography scan in adults at a tertiary care center.

Background: The introduction provides an in-depth understanding of the acetabulum's anatomical structure and its significance in hip joint biomechanics. It highlights the variability in acetabular morphology among normal individuals, emphasizing the importance of establishing normal ranges for accurate diagnosis of acetabular deformities. The section also underscores the role of geographical, racial, and anatomical factors in influencing acetabular parameters, crucial for orthopedic interventions and surgical outcomes like total hip arthroplasty. Furthermore, it discusses the limitations of traditional imaging methods and the necessity of advanced techniques like computed tomography (CT) scans for precise evaluation and preoperative planning in hip surgeries. Materials and methods: The study adopted a cross-sectional design at a tertiary care center, enrolling 94 participants using purposive sampling for CT evaluation of acetabular morphology. Morphometric parameters including center edge angle of Wiberg, acetabular angle of Sharp, acetabular version, acetabular depth, and joint space width were measured using CT scans, while BMI categorization and statistical analyses were conducted to explore gender-based and side-based differences and correlations with BMI and age. Results: The study included 94 patients with ages ranging from 20 to 82 years (mean age: 49±15 years), predominantly in the 41-50 years age group. Female participants slightly outnumbered males. The mean BMI was 23.5±3.2 kg/m2, with variations across different age and BMI categories. Most morphometric parameters showed no significant differences between sexes or sides but did correlate with age and BMI, notably the center edge angle positively correlating with BMI in males. Conclusions: The study found correlations between morphometric parameters of the acetabulum and both age and BMI. Specifically, the center edge angle demonstrated a positive correlation with BMI in males and a weak positive correlation with age. Acetabular angle showed a negative correlation with BMI, highlighting potential implications for understanding hip joint health and conditions related to BMI changes.

Lung carcinoma with adrenal metastasis and inferior vena cava thrombosis in an elderly patient with decompensated chronic liver disease: a case report.

Introduction: Managing patients with complex comorbidities poses significant diagnostic and therapeutic challenges. This case report details a 65-year-old male with a history of decompensated chronic liver disease (CLD) and portal hypertension, who presented with symptoms suggestive of liver disease exacerbation. He was later diagnosed with primary lung malignancy and extensive thrombosis, including the inferior vena cava (IVC) and heart chambers, a rare finding. Case presentation: A 65-year-old man with a history of smoking, alcohol consumption, and chronic liver disease presented with severe pain in the upper right quadrant, dyspnea, weakness, loss of appetite, and unintentional weight loss. Medical assessments revealed decompensated CLD with elevated bilirubin levels, low albumin, and an elevated INR. Imaging showed lung cancer with metastasis to the adrenal gland and a large IVC thrombus extending to the heart chambers. The patient decided to pursue palliative care. Discussion: When dealing with primary lung cancer and adrenal metastasis, it's important to thoroughly assess atypical presentations for IVC thrombus. Even with advances in imaging and treatments, managing IVC thrombus related to cancer is still difficult and requires a team approach. This case highlights underdiagnosis in areas with limited resources, emphasizing the need for timely advanced diagnostics such as CT and MR imaging. Conclusion: This case highlights the complexities of diagnosing and managing patients with multiple conditions. It emphasizes the need for patient-centered care and the importance of ongoing research to develop effective diagnostic and treatment strategies for conditions like IVC thrombus in the context of malignancy.

Lutembacher syndrome presenting as heart failure in an old female from rural Nepal: a case report.

Introduction and significance: Lutembacher syndrome (LS), combining atrial septal defect (ASD) and mitral stenosis (MS), is rare, particularly in rural areas. This case presents a 55-year-old Nepalese woman with LS symptoms; however, financial constraints hindered surgical treatment, highlighting LS challenges and the need for early intervention in resource-limited settings. Case presentation: A 55-year-old woman from rural Nepal presented with 30-day leg swelling and shortness of breath. Apart from autosomal dominant polycystic kidney disease (ADPKD) and smoking, she had no significant comorbidities. Clinical examination revealed severe mitral stenosis and an ASD, but financial limitations prevented surgery. Clinical discussion: LS is rarer in regions with low rheumatic heart disease (RHD) prevalence like Nepal. This case, despite rarity, delayed presentation, and financial barriers, emphasizes early intervention's importance. While rheumatic fever wasn't confirmed, clinical and echocardiographic findings suggest rheumatic mitral stenosis. The patient's surgery reluctance due to finances highlights resource limitations' impact. Conclusion: This Nepalese LS case highlights its complexity and management challenges, especially in resource-limited settings. It stresses early intervention's importance and the impact of financial constraints on patient care. The study urges improved healthcare access and alternative funding in high RHD-prevalence regions.

Awareness of personal safety among frontline healthcare workers working in COVID ward of BPKIHS during COVID-19 pandemic: a cross-sectional study authors.

Background: Frontline healthcare workers are at higher risk for COVID-19 infection and due to lack of availability of adequate personal protective equipment (PPE), lack of knowledge and good practices results in more deaths each year due to occupational accidents and diseases. Objective: The aim of the study was to assess the awareness of personal safety, the association between the level of awareness with selected socio-demographic variables and to identify the correlation between knowledge and practice of personal safety. Materials and methods: A descriptive cross-sectional study design was conducted among 106 Frontline Healthcare workers who have worked in the COVID ward. The study was conducted between 7 August 2022 and June 2023. A convenient sampling technique was used for sample selection. A validated self-administered questionnaire was used to assess the awareness of personal safety. Descriptive statistics (mean, SD frequency and percentage) and inferential statistics (χ2 and Spearman's correlation rank) were used for the data analysis. Results: Among the respondents, there were 38 doctors and 68 nurses. The majority of the respondents had a moderate level of knowledge (79.2%) and practice (52.8%) with a mean score of 13.52±2.10 and 14.51± 2.35, respectively. Doctors have slightly higher levels of knowledge (14.01±1.62) and practice (14.57±2.07) as compared to Nurses (13.19±2.27, 14.48±2.5), respectively. Knowledge was found to be associated with the education level and age of the respondents, and practice has a significant association with training/demonstration with a P value of less than 0.05. Knowledge and practice were found to have a partial positive correlation (r value of 0.27). Conclusion: This study concluded that those having higher levels of education had good levels of knowledge and those who have attended formal or informal training or demonstrations regarding personal safety had good practices regarding personal safety.

Unmasking Sturge-Weber syndrome in adulthood: a case with extrafacial port-wine stain and delayed neurological symptoms.

Background: Sturge-Weber syndrome (SWS) is a rare neurocutaneous disorder characterized by a facial port-wine birthmark, leptomeningeal angiomatosis, and glaucoma. This case report highlights the challenges of diagnosing SWS when presenting with atypical features. Here, the authors present a 55-year-old man with an extrafacial port-wine stain and delayed-onset seizures, deviating from the classic triad. Case presentation: A 55-year-old man presented with a recent seizure and a characteristic port-wine birthmark extending beyond the typical facial region. Neurological examination revealed no weakness, speech difficulties, or coordination problems. Ophthalmological examination didn't reveal glaucoma. Limited resources restricted access to advanced imaging like MRI scans. However, based on the constellation of clinical findings, including the facial birthmark with angiomatosis and the new-onset seizure, the patient received a diagnosis of SWS. Treatment with Levetiracetam was initiated to prevent future seizures, and patient education on managing diabetes and hypertension was provided. Clinical discussion: This case underscores the importance of considering SWS in diagnosing adult-onset seizures, especially with a characteristic facial birthmark. The delayed presentation and isolated seizure suggest potentially less severe brain involvement. Resource limitations necessitated a clinical diagnosis and treatment with readily available medications. Conclusion: This case highlights the challenges of diagnosing atypical SWS presentations. Early diagnosis is crucial for prompt management and improved patient outcomes. Future research should focus on developing robust diagnostic tools and exploring novel treatment options for atypical SWS presentations.

Foix-Chavany-Marie syndrome due to unilateral opercular infarction-A case report.

Key Clinical Message: Unilateral opercular lesions can result in Foix-Chavany-Marie syndrome, which is marked by acute anarthria, automatic-voluntary movement dissociation-most notably the absence of voluntary facial and tongue movements-and a generally better prognosis. Better patient outcomes are mostly dependent on early detection, management, and rehabilitation. Abstract: Opercular syndrome is a rare neurological disorder caused by bilateral or unilateral lesions of the operculum that result in symptoms related to speech and swallowing difficulties with dissociation of automatic-voluntary movements in affected muscles. 78-year-old female presented with acute onset dysarthria, left sided facial deviation and difficulties in chewing, speaking, and swallowing. CT head revealed ischemic changes in left frontal operculum and was diagnosed with the unilateral opercular syndrome. The case was managed according to ischemic stroke protocol. The patient was discharged after 7 days of hospital stay, with MRS 2, NIHSS 9 and secondary stroke preventive measures. At 4 months follow-up, her MRS was 1, with mild dysarthria, that could be understood, and her swallowing improved to some amount of drooling while feeding. Early recognition, treatment, and rehabilitation play important role in prompt improvement of symptoms.

Tobacco use and its associated factors among students of medical college at tertiary care center of Eastern Nepal.

BACKGROUND: Despite declining smoking prevalence globally, South Asia faces a rising burden. In Nepal, existing tobacco control laws haven't curbed use, with 28.9% of young adults engaging in tobacco use. This study investigates tobacco use and associated factors among medical, dental, and nursing students at a Nepalese tertiary care center. OBJECTIVE: We aimed to assess tobacco use prevalence and identify factors associated with it among future healthcare professionals, considering their distinct roles in tobacco control. Medical students can contribute through clinical counseling and public health advocacy, dental students through oral health education, and nursing students through patient education and community outreach. METHODS: A cross-sectional study involving 427 medical, dental, and nursing students was conducted. Data was collected using online questionnaires distributed via email and social media. Descriptive statistics and Chi-square tests were used for analysis. RESULTS: The study found that 45% of participants were aged 22-25, with females comprising the majority (53.2%). Nearly half (49.2%) belonged to the medical faculty, and 24.4% were in their first year. Furthermore, among those who smoke, 53% reported smoking less than 5 cigarettes daily. The analysis revealed significant associations between smoking with age (p = 0.01), year of study (p = 0.001), parental smoking history (p = 0.001), and having friends who smoke (p = 0.001). CONCLUSION: Our findings highlight the moderate prevalence of cigarette smoking among medical students, with family and friends emerging as major influences. Stress relief was a common reason, particularly among young females and first-year students. These results emphasize the urgent need for comprehensive tobacco control programs within medical institutions to equip future healthcare professionals to effectively address smoking issues.

Varicella pneumonia in an immunocompetent child: A case report.

Varicella-zoster virus (VZV) is a type of herpes virus that causes varicella (primary infection) and herpes zoster/shingles (due to reactivation of latent infection). Usually a benign and a self-limited illness, the illness sometimes can result in severe complications in both immunocompetent and immunocompromised persons. Varicella Pneumonia as a complication of herpes zoster is a rare event, with reports primarily concerning immunocompromised individuals. Here we report a 14-year-old female who developed a secondary bacterial infection of the skin lesions and varicella pneumonia associated with VZV infection. The patient presented with multiple painful vesicles that later turned into pustular lesions over the right cheek with erosions and hemorrhagic crusting. Swelling involving the right half of both upper and lower lips was present. She developed a fever, cough, and shortness of breath after two days of the presence of vesico-pustular lesions. A diagnosis of Pneumonia was made based on symptoms of fever and cough and findings on chest x-ray. This case highlights, though rare, varicella pneumonia has a high rate of respiratory failure, but early diagnosis with prompt administration of antiviral medications can improve outcomes.

Perineurial Barrier Glia Physically Respond to Alcohol in an Akap200-Dependent Manner to Promote Tolerance.

Ethanol is the most common drug of abuse. It exerts its behavioral effects by acting on widespread neural circuits; however, its impact on glial cells is less understood. We show that Drosophila perineurial glia are critical for ethanol tolerance, a simple form of behavioral plasticity. The perineurial glia form the continuous outer cellular layer of the blood-brain barrier and are the interface between the brain and the circulation. Ethanol tolerance development requires the A kinase anchoring protein Akap200 specifically in perineurial glia. Akap200 tightly coordinates protein kinase A, actin, and calcium signaling at the membrane to control tolerance. Furthermore, ethanol causes a structural remodeling of the actin cytoskeleton and perineurial membrane topology in an Akap200-dependent manner, without disrupting classical barrier functions. Our findings reveal an active molecular signaling process in the cells at the blood-brain interface that permits a form of behavioral plasticity induced by ethanol.

Suppression of the reticuloendothelial system using λ-carrageenan to prolong the circulation of gold nanoparticles.

AIM: Gold nanoparticles are employed for imaging and treatment of surgically inaccessible tumors owing to their inherent optical absorption and ability to extravasate through intravenous distribution. These nanoparticles are cleared from the blood by the reticuloendothelial system (RES) as expected given their size. MATERIALS & METHODS: This study demonstrates the effects of RES blockade through the intravenous administration of λ-carrageenan, resulting in a decrease in the median clearance rate from 18.9 (95% CrI: 15.9-22.6) to 11.2 (95% CrI: 8.8-13.9) µl/min and an increase in nanoparticle circulation half-life t(½)( = 264 ± 73 vs 160 ± 22 min; p < 0.01). RESULTS: This 59.3% decrease in clearance is greater than the 15% previously reported for liposomes [ 1 ]. CONCLUSION: The primary benefit of nontoxic RES blockade is to increase the circulation time, where traditional particle modification is ineffective or impractical.

Feasibility of Energy Dispersive X-Ray Fluorescence Determination of Gold in Soft Tissue for Clinical Applications.

The feasibility of using EDXRF for a rapid quantitative analysis of gold in tumor tissue has been investigated. The protocol described here demonstrates that sample biopsies can be analyzed in as little as 8 hours, with minimal sample preparation. Samples were prepared by drying a 35 µL aliquot of tissue dissolved in KOH in a standard EDXRF cup on a Prolene® support, producing a thin sample. Calibration curves of XRF peak intensity (CPS/mA) to the gold concentration (0-50 PPM) were prepared for liver, tumor, and a mix of tissue types. A linear regression demonstrated an R2 correlation of 0.93. Analysis of experimental samples showed that gold accumulation in tumors (5.8-41.3 PPM) was in agreement with previous studies, where samples were processed using INAA or ICP-MS. This report provides guidance for elemental analysis of gold in tissue in a shorter time span, showing potential for its use in a clinical setting.