Digital Biomarkers for Alzheimer’s Disease

There is a growing interest in developing new biomarkers using digital devices. The primary purpose of digital biomarkers is to obtain features based on multi-dimensional data such as multiple data sources from various digital devices and time-series data reflecting temporal changes. Therefore, digital biomarkers can be used to measure the behavioral patterns of individuals in their daily lives in contrast to traditional biomarkers that reflect specific time points in clinical or laboratory settings. However, there are still several limitations including validation and interpretation. This article reviews the potential of digital biomarkers, explores previous studies on digital phenotypes related to Alzheimer’s disease, and discusses the future challenges of implementing digital biomarkers in the medical field.

Core indicators related to the elimination of hepatitis B and C virus infection in South Korea: A nationwide study

Background/Aims@#To eliminate hepatitis B virus (HBV) and hepatitis C virus (HCV) according to the World Health Organization (WHO) criteria in 2021, this study investigated the national core indicators representing the current status of viral hepatitis B and C in South Korea. @*Methods@#We analyzed the incidence, linkage-to-care, treatment, and mortality rates of HBV and HCV infection using the integrated nationwide big data of South Korea. @*Results@#According to data from 2018–2020, the incidence of acute HBV infection in South Korea was 0.71 cases per 100,000 population; tthe linkage-to-care rate was only 39.4%. Among those who need hepatitis B treatment, the treatment rate was 67.3%, which was less than 80% reported in the WHO program index. The annual liver-related mortality due to HBV was 18.85 cases per 100,000 population, exceeding the WHO target of four; the most frequent cause of death was liver cancer (54.1%). The annual incidence of newly diagnosed HCV infection was 11.9 cases per 100,000 population, which was higher than the WHO impact target of five. Among HCV-infected patients, the linkage-to-care rate was 65.5% while the treatment rate was 56.8%, which were below the targets of 90% and 80%, respectively. The liver-related annual mortality rate due to HCV infection was 2.02 cases per 100,000 population. @*Conclusions@#Many of the current indicators identified in the Korean population did not satisfy the WHO criteria for validation of viral hepatitis elimination. Hence, a comprehensive national strategy should be urgently developed with continuous monitoring of the targets in South Korea.

Cost-Effectiveness of All-Oral Regimens for the Treatment of Multidrug-Resistant Tuberculosis in Korea: Comparison With Conventional Injectable-Containing Regimens

Background@#Regimens for the treatment of multidrug-resistant tuberculosis (MDR-TB) have been changed from injectable-containing regimens to all-oral regimens. The economic effectiveness of new all-oral regimens compared with conventional injectable-containing regimens was scarcely evaluated. This study was conducted to compare the cost-effectiveness between all-oral longer-course regimens (the oral regimen group) and conventional injectablecontaining regimens (the control group) to treat newly diagnosed MDR-TB patients. @*Methods@#A health economic analysis over lifetime horizon (20 years) from the perspective of the healthcare system in Korea was conducted. We developed a combined simulation model of a decision tree model (initial two years) and two Markov models (remaining 18 years, sixmonth cycle length) to calculate the incremental cost-effectiveness ratio (ICER) between the two groups. The transition probabilities and cost in each cycle were assumed based on the published data and the analysis of health big data that combined country-level claims data and TB registry in 2013–2018. @*Results@#The oral regimen group was assumed to spend 20,778 USD more and lived 1.093 years or 1.056 quality-adjusted life year (QALY) longer than the control group. The ICER of the base case was calculated to be 19,007 USD/life year gained and 19,674 USD/QALY. The results of sensitivity analyses showed that base case results were very robust and stable, and the oral regimen was cost-effective with a 100% probability for a willingness to pay more than 21,250 USD/QALY. @*Conclusion@#This study confirmed that the new all-oral longer regimens for the treatment of MDR-TB were cost-effective in replacing conventional injectable-containing regimens.

Bilateral Thalamic Infarction Related to Artery of Percheron with Microembolic Signal

The artery of Percheron (AOP) is an uncommon variant of the posterior cerebral artery that supplies blood to the paramedian thalamus and rostral midbrain. AOP is often difficult to recognize with intracranial magnetic resonance angiography due to its small size. Although a number of case reports of AOP occlusion have been published, cause of the occlusion is mostly unclear. We experienced a case of AOP occlusion which resulted in bilateral thalamic infarction. It was most likely caused by a microembolism through right-left shunt.

Clinical management guidelines for Friedreich ataxia: best practice in rare diseases.

BACKGROUND: Individuals with Friedreich ataxia (FRDA) can find it difficult to access specialized clinical care. To facilitate best practice in delivering healthcare for FRDA, clinical management guidelines (CMGs) were developed in 2014. However, the lack of high-certainty evidence and the inadequacy of accepted metrics to measure health status continues to present challenges in FRDA and other rare diseases. To overcome these challenges, the Grading of Recommendations Assessment and Evaluation (GRADE) framework for rare diseases developed by the RARE-Bestpractices Working Group was adopted to update the clinical guidelines for FRDA. This approach incorporates additional strategies to the GRADE framework to support the strength of recommendations, such as review of literature in similar conditions, the systematic collection of expert opinion and patient perceptions, and use of natural history data. METHODS: A panel representing international clinical experts, stakeholders and consumer groups provided oversight to guideline development within the GRADE framework. Invited expert authors generated the Patient, Intervention, Comparison, Outcome (PICO) questions to guide the literature search (2014 to June 2020). Evidence profiles in tandem with feedback from individuals living with FRDA, natural history registry data and expert clinical observations contributed to the final recommendations. Authors also developed best practice statements for clinical care points that were considered self-evident or were not amenable to the GRADE process. RESULTS: Seventy clinical experts contributed to fifteen topic-specific chapters with clinical recommendations and/or best practice statements. New topics since 2014 include emergency medicine, digital and assistive technologies and a stand-alone section on mental health. Evidence was evaluated according to GRADE criteria and 130 new recommendations and 95 best practice statements were generated. DISCUSSION AND CONCLUSION: Evidence-based CMGs are required to ensure the best clinical care for people with FRDA. Adopting the GRADE rare-disease framework enabled the development of higher quality CMGs for FRDA and allows individual topics to be updated as new evidence emerges. While the primary goal of these guidelines is better outcomes for people living with FRDA, the process of developing the guidelines may also help inform the development of clinical guidelines in other rare diseases.

The effect of choline alphoscerate on non spatial memory and neuronal differentiation in a rat model of dual stress.

Choline alphoscerate (α-GPC) is a choline-based compound and acetylcholine precursor commonly found in the brain; it has been known to be effective in treating neuronal injury and increasing the levels of acetylcholine (Ach) and brain-derived neurotrophic factor (BDNF) which in turn enhances memory and cognitive function. This study was designed to establish rat models of dual stress using noise and restraint in order to investigate the effect of α-GPC on cognitive function and neuronal differentiation after dual stress. The rats were randomly divided into four groups as follows: a control group (CG), a control with α-GPC group (CDG), a noise-restraint stress group (NRSG), and a noise-restraint stress with α-GPC group (NRSDG). Experimental groups were exposed to a 110 dB sound pressure level (SPL) white band noise and restraint at the same time for 3 h/day for 7 days. Alpha-GPC (400 mg/kg) was administered orally after stress exposure for 7 days. NRSG showed decreased memory function, increased stress hormone, hearing loss, and neuronal damage of the brain. In the hippocampus of NRSG, significantly increased expression of IL-1ß and decreased expression of both choline acetyltransferase (ChAT) and BDNF were observed. On the contrary, NRSDG showed better memory function compared to NRSG, which indicates the neuroprotective effect of α-GPC. In addition, NRSDG showed decreased immune response and increased ChAT and BDNF expression as well as neuroblast expression in the hippocampus, which suggests that α-GPC enhances BDNF expression and protects the activity of immature cells in the hippocampus. To the best of our knowledge, this is the first study to show the protective effect of α-GPC on cognitive dysfunction by promotion of neuronal differentiation in an animal model of stress.

A cost-effectiveness study of universal screening for hepatitis C virus infection in South Korea: A societal perspective

Background/Aims@#This study aimed to evaluate the cost-effectiveness of hepatitis C virus (HCV) screening compared to no screening in the Korean population from societal and healthcare system perspectives. @*Methods@#A published decision-tree plus Markov model was used to compare the expected costs and quality-adjusted life years (QALY) between one-time universal HCV screening and no screening in the population aged 40–65 years using the National Health Examination (NHE) program. Input parameters were obtained from analyses of the National Health Insurance claims data, Korean HCV cohort data, or from the literature review. The population aged 40–65 years was simulated in a model spanning a lifetime from both the healthcare system and societal perspectives, which included the cost of productivity loss due to HCV-related deaths. The incremental cost-effectiveness ratio (ICER) between universal screening and no screening was estimated. @*Results@#The HCV screening strategy had an ICER of $2,666/QALY and $431/QALY from the healthcare system and societal perspectives, respectively. Both ICERs were far less than the willingness-to-pay threshold of $25,000/QALY, showing that universal screening was highly cost-effective compared to no screening. In various sensitivity analyses, the most influential parameters on cost-effectiveness were the antibodies to HCV (anti-HCV) prevalence, screening costs, and treatment acceptance; however, all ICERs were consistently less than the threshold. If the anti-HCV prevalence was over 0.18%, screening could be cost-effective. @*Conclusions@#One-time universal HCV screening in the Korean population aged 40–65 years using NHE program would be highly cost-effective from both healthcare system and societal perspectives.

Analysis of Medical Use and Treatment Costs of Hepatocellular Carcinoma Patients Using National Patient Sample Data

Background@#With increasing economic evaluation studies on the treatment of or screening tools for liver diseases that cause hepatocellular carcinoma (HCC), interest in the analysis of the medical utilization and costs of HCC treatment is increasing. Therefore, we aimed to estimate the medical utilization and costs of HCC patients, and calculate the cost of main procedures for HCC treatment, including liver transplant (LT), hepatic resection (HR), radiofrequency ablation (RFA), and transarterial chemoembolization (TACE). @*Methods@#We analyzed claim data from January to December 2018 from the Health Insurance and Review and Assessment Service–National Patient Sample (HIRA-NPS-2018) dataset, including data of patients diagnosed with HCC (Korean Standard Classification of Diseases code C22.0) who had at least one inpatient claim for HCC. @*Results@#A total of 715 HCC patients were identified. In 2018, the yearly average medical cost per HCC patient was ₩18,460K (thousand), of which ₩14,870K was attributed to HCC. Among the total medical costs of HCC patients, the inpatient cost accounted for the largest portion of both the total medical and HCC-related costs. The major procedures of HCC treatment occurred most frequently in the order of TACE, RFA, HR, and LT. The average medical cost per treatment episode was the highest for LT (₩87,280K), followed by HR (₩10,026K), TACE (₩4,047K), and RFA (₩2,927K). @*Conclusion@#By identifying the medical costs of HCC patients and the costs of the main procedures of HCC treatment, our results provide basic information that could be utilized for cost estimation in liver disease-related economic evaluation studies.

Analysis of Medical Use and Treatment Costs of Hepatocellular Carcinoma Patients Using National Patient Sample Data

Background@#With increasing economic evaluation studies on the treatment of or screening tools for liver diseases that cause hepatocellular carcinoma (HCC), interest in the analysis of the medical utilization and costs of HCC treatment is increasing. Therefore, we aimed to estimate the medical utilization and costs of HCC patients, and calculate the cost of main procedures for HCC treatment, including liver transplant (LT), hepatic resection (HR), radiofrequency ablation (RFA), and transarterial chemoembolization (TACE). @*Methods@#We analyzed claim data from January to December 2018 from the Health Insurance and Review and Assessment Service–National Patient Sample (HIRA-NPS-2018) dataset, including data of patients diagnosed with HCC (Korean Standard Classification of Diseases code C22.0) who had at least one inpatient claim for HCC. @*Results@#A total of 715 HCC patients were identified. In 2018, the yearly average medical cost per HCC patient was ₩18,460K (thousand), of which ₩14,870K was attributed to HCC. Among the total medical costs of HCC patients, the inpatient cost accounted for the largest portion of both the total medical and HCC-related costs. The major procedures of HCC treatment occurred most frequently in the order of TACE, RFA, HR, and LT. The average medical cost per treatment episode was the highest for LT (₩87,280K), followed by HR (₩10,026K), TACE (₩4,047K), and RFA (₩2,927K). @*Conclusion@#By identifying the medical costs of HCC patients and the costs of the main procedures of HCC treatment, our results provide basic information that could be utilized for cost estimation in liver disease-related economic evaluation studies.

Effect of saccharin on inflammation in 3T3-L1 adipocytes and the related mechanism

BACKGROUND/OBJECTIVES: Excessive intake of simple sugars induces obesity and increases the risk of inflammation. Thus, interest in alternative sweeteners as a sugar substitute is increasing. The purpose of this study was to determine the effect of saccharin on inflammation in 3T3-L1 adipocytes.MATERIALS/METHODS: 3T3-L1 preadipocytes were differentiated into adipocytes. The adipocytes were treated with saccharin (0, 50, 100, and 200 µg/mL) for 24 h. Inflammation was induced by exposure of treated adipocytes to lipopolysaccharide (LPS) for 18 h and cell proliferation was measured. The concentration of nitric oxide (NO) was measured by using Griess reagent. Protein expressions of nuclear factor kappa B (NF-κB) and inhibitor κB (IκB) were determined by western blot analysis. The mRNA expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin 1β (IL-1β), interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α) were determined by real-time PCR.RESULTS: Compared with the control group, the amount of NO and the mRNA expression of iNOS in the LPS-treated group were increased by about 17.6% and 46.9%, respectively, (P < 0.05), and those parameter levels were significantly decreased by saccharin treatment (P < 0.05). Protein expression of NF-κB was decreased and that of IκB was increased by saccharin treatment (P < 0.05). Saccharin decreased the mRNA expression of COX-2 and the inflammation cytokines (IL-1β, IL-6, MCP-1, and TNF-α) (P < 0.05).CONCLUSIONS: The results of this study suggest that saccharin can inhibit LPS-induced inflammatory responses in 3T3-L1 adipocytes via the NF-κB pathway.

Analysis of Medical Use and Costs of Liver Transplant Patients Using National Patients Sample Data

BACKGROUND: Patients experience significant differences in aspects of mortality, quality of life, and costs between during the year of receiving liver transplant (LT) and the subsequent years (post-LT). This study aimed to estimate the medical utilization and cost of LT for patients compared to post-LT patients by using a recent National Patient Sample (NPS) data provided by the Korean Health Insurance Review and Assessment Service (HIRA). METHODS: This study used a subset of the 2015 HIRA-NPS. Patient claims data that included Z944 (Korean Standard Classification of Diseases code for LT status) were selected. Within the selected data, LT patients were identified based on whether the national health insurance number code of Q80 (procedure code for LT surgery) was included, and they were compared to post-LT patients. RESULTS: In the analysis, 330 patients were included. The average cost per patient was 90,066±36,959 thousand KRW and 10,557±9,668 thousand KRW for LT and post-LT patients, respectively. Especially, LT patients' costs for injection/procedure, surgery/treatment, and examination were higher than other costs, being 35,983±18,115 thousand KRW, 28,246±9,408 thousand KRW, and 12,131±6,604 thousand KRW, respectively. For inpatients, the average number of hospitalized days was 63.5±66.0 days for LT patients and 22.3±35.1 days for post-LT patients. CONCLUSION: Compared to post-LT patients, LT patients had higher costs, especially for injection/procedure, surgery/treatment, and examination. Additionally, the LT group had longer hospitalization duration and higher costs for their hospital admission, whereas they did not show a significant difference in number of visits and medical costs for outpatient-care.

Computer-Aided Diagnosis of Thyroid Nodules via Ultrasonography: Initial Clinical Experience

OBJECTIVE: To prospectively evaluate the diagnostic performance of computer-aided diagnosis (CAD) for detection of thyroid cancers via ultrasonography (US). MATERIALS AND METHODS: This study included 50 consecutive patients with 117 thyroid nodules on US during the period between June 2016 and July 2016. A radiologist performed US examinations using real-time CAD integrated into a US scanner. We compared the diagnostic performance of radiologist, the CAD system, and the CAD-assisted radiologist for the detection of thyroid cancers. RESULTS: The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the CAD system were 80.0, 88.1, 83.3, 85.5, and 84.6%, respectively, and were not significantly different from those of the radiologist (p > 0.05). The CAD-assisted radiologist showed improved diagnostic sensitivity compared with the radiologist alone (92.0% vs. 84.0%, p = 0.037), while the specificity and PPV were reduced (85.1% vs. 95.5%, p = 0.005 and 82.1% vs. 93.3%, p = 0.008). The radiologist assisted by the CAD system exhibited better diagnostic sensitivity and NPV than the CAD system alone (92.0% vs. 80.0%, p = 0.009 and 93.4% vs. 88.9%, p = 0.013), while the specificities and PPVs were not significantly different (88.1% vs. 85.1%, p = 0.151 and 83.3% vs. 82.1%, p = 0.613, respectively). CONCLUSION: The CAD system may be an adjunct to radiological intervention in the diagnosis of thyroid cancer.

Effect of Doctor and Device Manager on Adherence with Positive Airway Pressure Therapy in Obstructive Sleep Apnea Patients

BACKGROUND AND OBJECTIVES: Although many studies have assessed factors related to adherence of PAP therapy, there were no studies about factors related to doctors or device managers. The purpose of this study was to investigate the relationship between PAP therapy adherence and doctor or device manager. SUBJECTS AND METHODS: Between February 2013 and June 2015, 163 patients newly diagnosed with moderate to severe OSA in one of five hospitals were enrolled in this study. All patients received 4 weeks of PAP treatment with intervention consisting of mechanical support and motivation by doctor and device manager. Data from the PAP device were obtained following a minimum of an initial 30 days, with adherence defined as >4 h/night on 70% of nights. RESULTS: After 30 days, total adherence rate to PAP therapy was 35.6% (n=58). The adherence rate of device manager ① was 26.3% (31/118), and that of device manager ② was 60% (27/45), and there was statistically significant difference between the two device managers. Furthermore, there were statistically significant differences in the adherence to PAP therapy ranging from 85.6% to 0.0% according to doctor. CONCLUSION: Our study demonstrates that the device manager and doctor may be important factors for good adherence to PAP therapy in patients with OSA.

The Significance of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Markers for Prognosis in Idiopathic Sudden Sensorineural Hearing Loss / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The cause of idiopathic sudden sensorineural hearing loss (ISSNHL) is still unclear, but recently, chronic inflammation and thrombosis have received attention. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are some of the markers that show the state of inflammation and ischemia, which are measured routinely in the complete blood cell count (CBC) test. The aim of this study were to investigate the relevance of NLR and PLR with ISSNHL. SUBJECTS AND METHOD: Enrolled in our retrospective analysis were 103 patients diagnosed with ISSNHL. Blood samples were taken from the patients and hearing assessments were performed. NLR and PLR were calculated using the CBC results. Then the patients were divided into 4 groups using Sigel's criteria according to their response to the treatment, which were again classified two groups, the “recovered” and “unrecovered” group. RESULTS: NLR, PLR, and neutrophil values of the unrecovered group were significantly higher than the recovered group (p=0.002, p=0.009, and p=0.038, respectively). On the other hand, lymphocyte values were significantly higher in the recovered group (p=0.007). After adjustment in a multivariate logistic regression analysis, NLR was associated with the recovery of ISSNHL (Odds ratio=1.290, p=0.042). In addition, NLR and PLR values were also significantly different between the groups classified by the Sigel's criteria (p=0.009 and p=0.029, respectively). CONCLUSION: PLR values may be useful in predicting hearing recovery after treatment in patients with ISSNH. It is also expected to be a potential marker for predicting the prognosis and determining further treatment options.

Cancer Prevalence among Physicians in Korea: A Single Center Study / 가정의학회지

BACKGROUND: There is little research regarding whether working as a physician affects cancer risk. Moreover, there is no research on cancer prevalence among physicians in Korea. This study utilized the Korea National Cancer Incidence Database to determine whether the prevalence of cancer among physicians differs from the prevalence of cancer within the general population. METHODS: We analyzed the medical records of a representative sample of 382 doctors who underwent a health examination between 2010 and 2013 at a health examination center in a Ewha Womans University Medical Center.Cancer incidence was measured as cases that were eventually diagnosed as cancer according to a biopsy. RESULTS: We collected medical records from 382 physicians (mean age, 51.9±8.1 years) and calculated the standardized prevalence ratios compared to the general population. Thirty physicians (9 male and 21 female) were identified as having cancer. Physicians had a significantly higher prevalence of cancer compared to the general population.Cancer prevalence in male physicians was found to be 2.47 times higher than the prevalence expected within the general population (P=0.006). Among female physicians, cancer prevalence was 3.94 times higher than that in the general population (P<0.001). CONCLUSION: This study revealed that physicians had a higher prevalence of cancer compared to the general population in Korea, which suggests that there may be a problem present in the health care of physicians. Changes to the working environment of physicians will be needed to reduce the high prevalence of cancer among physicians.

Analysis of Medical Use and Costs Related to the Management of Liver Cirrhosis Using National Patients Sample Data

BACKGROUND: Liver cirrhosis causes substantial socio-economic burden and is one of the major severe liver diseases in Korea. Nonetheless, there is only a few studies that analyzes disease burden of liver cirrhosis in Korea. Such study must be carried out due to its increasing need from the invention of new drugs for chronic hepatitis and demand for cost-effectiveness analyses. METHODS: Patient sample data with ensured representativeness was analyzed retrospectively to compare the medical costs and uses for patients with compensated cirrhosis and decompensated cirrhosis. Patient claims data that include K74 and K703 from the year of 2014 were selected. Within the selected data, decompensated cirrhosis patient was identified if complications such as ascites (R18), encephalopathy (B190), hepatic failure (K72), peritonitis (K65), or esophageal varices (I85) were included, and they were compared to compensated cirrhosis patients. RESULTS: 6,565 patients were included in the analysis. The average cost per patient was 6,471,020 (SD 8,848,899) KRW and 2,173,203 (4,220,942) KRW for decompensated cirrhosis and compensated cirrhosis, respectively. For inpatients, the average hospitalized days was 38.0 (56.4) days and 27.2 (57.2) days for decompensated cirrhosis and compensated cirrhosis, respectively. For outpatients, the average number of visits was 8.7 (9.1) days and 5.3 (7.5) days for compensated cirrhosis and decompensated cirrhosis, respectively. CONCLUSION: Compared to compensated cirrhosis patients, decompensated cirrhosis patients had higher costs, especially for hospitalization, injection, examination, and drugs administrated within medical institutions.

Comparative Effectiveness of Biologic DMARDs in Rheumatoid Arthritis Patients with Inadequate Response to conventional DMARDs: Using a Bayesian Network Meta-analysis

BACKGROUND: Biologic disease-modifying antirheumatic drugs (bDMARDs) extend the treatment choices for rheumatoid arthritis patients with insufficient response or intolerance to conventional DMARDs (cDMARDs). These agents have considerable efficacy compared with conventional DMARDs, but only a few head-to-head comparisons among these agents have been performed. The objective of this systematic review and network meta-analysis (NMA) was to compare the relative efficacy of Certolizumab with conventional DMARD to licensed bDMARD with cDMARD therapy for patients who failed to prior cDMARD treatment under the condition of the reimbursement coverage criteria in Korea. METHODS: A systematic review was conducted using MEDLINE and Cochrane library. Key endpoints were the American College of Rheumatology (ACR) responses of 20/50/70 at six months. Bayesian outcomes were calculated as median of treatment effect, probability of the best, Odds Ratio (OR) and probability that OR was greater than one. RESULTS: Compared with other bDMARDs, Certolizumab were associated with higher or comparable ACR response rates; in ACR20, the OR (probability of OR>1) was 2.08 (92.6%) for Adalimumab, 1.86 (85.7%) for Etanercept, 1.89 (79.5%) for Golimumab, 2.36 (92.1%) for Infliximab, 1.79 (87.0%) for Abatacept, 1.74 (80.8%) for Rituximab and 1.82 (86.8%) for Tocilizaumab. In ACR50 and ACR70, the ORs did not present significant differences. CONCLUSION: Certolizaumab with cDMARD was more effective or comparable than other bDMARDs in patients who failed prior cDMARD treatment.

Stress and Sleep Disorder

The purpose of this study was to review potential, physiological, hormonal and neuronal mechanisms that may mediate the sleep changes. This paper investigates the literatures regarding the activity of the hypothalamic-pituitary-adrenal (HPA) axis, one of the main neuroendocrine stress systems during sleep in order to identify relations between stress and sleep disorder and the treatment of stress-induced insomnia. Sleep and wakefulness are regulated by the aminergic, cholinergic brainstem and hypothalamic systems. Activation of the HPA and/or the sympathetic nervous systems results in wakefulness and these hormones including corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), cortisol or corticosterone, noradrenaline, and adrenaline, are associated with attention and arousal. Stress-related insomnia leads to a vicious circle by activating the HPA system. An awareness of the close interaction between sleep and stress systems is emerging and the hypothalamus is now recognized as a key center for sleep regulation, with hypothalamic neurontransmitter systems providing the framework for therapeutic advances. An updated understanding of these systems may allow researchers to elucidate neural mechanisms of sleep disorder and to develop effective intervention for sleep disorder.

A Giant Sialolith in a Wharton's Duct: Report of Two Cases

SERIAL OSTEORADIONECROSIS ON BOTH SIDES OF MANDIBLE: A CASE REPORT