ABSTRACT
Background@#The treatment outcomes of patients with multidrug/rifampin-resistant (MDR/RR) tuberculosis (TB) are important indicators that reflect the current status of TB management and identify the key challenges encountered by TB control programs in a country. @*Methods@#We retrospectively evaluated the treatment outcomes as well as predictors of unfavorable outcomes in patients with MDR/RR-TB notified from 2011 to 2017, using an integrated TB database. @*Results@#A total of 7,226 patients with MDR/RR-TB were included. The treatment success rate had significantly increased from 63.9% in 2011 to 75.1% in 2017 (P < 0.001). Among unfavorable outcomes, the proportion of patients who failed, were lost to follow up, and were not evaluated had gradually decreased (P< 0.001). In contrast, TB-related death rate was not significantly changed (P= 0.513), while the non-TB related death rate had increased from 3.2% in 2011 to 11.1% in 2017 (P < 0.001). Older age, male sex, immigrants, low household income, previous history of TB treatment, and comorbidities were independent predictors of unfavorable outcomes. Of the 5,308 patients who were successfully treated, recurrence occurred in 241 patients (4.5%) at a median 18.4 months (interquartile range, 9.2–32.4) after completion treatment. @*Conclusion@#The treatment outcomes of patients with MDR/RR-TB has gradually improved but increasing deaths during treatment is an emerging challenge for MDR-TB control in Korea. Targeted and comprehensive care is needed for vulnerable patients such as the elderly, patients with comorbidities, and those with low household incomes.
ABSTRACT
The aim of this study was to develop evidence-based recommendations for determining the surgical extent in patients with locally invasive differentiated thyroid cancer (DTC). Locally invasive DTC with gross extrathyroidal extension invading surrounding anatomical structures may lead to several functional deficits and poor oncological outcomes. At present, the optimal extent of surgery in locally invasive DTC remains a matter of debate, and there are no adequate guidelines. On October 8, 2021, four experts searched the PubMed, Embase, and Cochrane Library databases; the identified papers were reviewed by 39 experts in thyroid and head and neck surgery. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence, and to develop and report recommendations. The strength of a recommendation reflects the confidence of a guideline panel that the desirable effects of an intervention outweigh any undesirable effects, across all patients for whom the recommendation is applicable. After completing the draft guidelines, Delphi questionnaires were completed by members of the Korean Society of Head and Neck Surgery. Twenty-seven evidence-based recommendations were made for several factors, including the preoperative workup; surgical extent of thyroidectomy; surgery for cancer invading the strap muscles, recurrent laryngeal nerve, laryngeal framework, trachea, or esophagus; and surgery for patients with central and lateral cervical lymph node involvement. Evidence-based guidelines were devised to help clinicians make safer and more efficient clinical decisions for the optimal surgical treatment of patients with locally invasive DTC.
ABSTRACT
Major depressive disorder is a leading cause of disability in more than 280 million people worldwide. Monoamine-based antidepressants are currently used to treat depression, but delays in treatment effects and lack of responses are major reasons for the need to develop faster and more efficient antidepressants. Studies show that ketamine (KET), a PCP analog, produces antidepressant effects within a few hours of administration that lasts up to a week. However, the use of KET has raised concerns about side effects, as well as the risk of abuse. 4 -F-PCP analog is a novel PCP analog that is also an NMDA receptor antagonist, structurally similar to KET, and might potentially elicit similar antidepressant effects, however, there has been no study on this subject yet. Herein, we investigate whether 4-F-PCP displays antidepressant effects and explored their potential therapeutic mechanisms. 4-F-PCP at 3 and 10 mg/kg doses showed antidepressant-like effects and repeated treatments maintained its effects. Furthermore, treatment with 4-F-PCP rescued the decreased expression of proteins most likely involved in depression and synaptic plasticity. Changes in the excitatory amino acid transporters (EAAT2, EAAT3, EAAT4) were also seen following drug treatment. Lastly, we assessed the possible side effects of 4-F-PCP after long-term treatment (up to 21 days). Results show that 4-F-PCP at 3 mg/kg dose did not alter the cognitive function of mice. Overall, current findings provide significant i
ABSTRACT
Objective@#Side effects from the coronavirus disease-2019 (COVID-19) vaccine, such as pain, headache, nausea, and fatigue, have caused vaccine hesitancy. Research on the effects of psychological factors on COVID-19 vaccine side effects is insufficient. This study aims to investigate the effect of psychological factors on COVID-19 vaccination side effects. @*Methods@#We recruited a total of 226 individuals registered for the COVID-19 vaccine in Seoul, South Korea, for this study. Participants completed a pre-vaccination questionnaire, including the 5C antecedents of vaccination, and a survey of psychological factors (Patient Health Questionnaire–9 [PHQ-9], Generalized Anxiety Disorder–7, Somatic symptom amplification scale [SSAS], and Illness Attitude Scale [IAS]). After vaccination, participants completed an online questionnaire regarding vaccine side effects at 20 minutes, three days, and seven days after vaccination. We added a discrete set of hierarchical variables with vaccine side effects as the dependent variable to the hierarchical regression analysis: demographics for Model 1, 5C antecedents of vaccination for Model 2, and psychological factors for Model 3. @*Results@#Our results indicated that the risk factors for side effects 20 minutes after vaccination were young age, high PHQ, and SSAS scores. Risk factors for side effects three days after vaccination were young age, high constraints, and calculation, and the risk factor for side effects at seven days was a high IAS score. @*Conclusion@#Our study confirmed that there is a significant relationship between psychological factors and COVID-19 vaccine side effects in chronological order. Psychosocial factors should be examined when assessing side-effect reactions to the COVID-19 vaccine.
ABSTRACT
Sleep deprivation or insomnia is one of the most common but neglected health conditions, with serious long-term consequences. In addition, insomnia is linked to poor work performance, impaired memory, and lack of concentration. Improving sleep quality is a crucial aspect of health care. Hypnotic agents, such as benzodiazepines, antidepressants, and antihistamines, are often used to enhance sleep quality; however, these medications often result in tolerance and dependence, resulting in withdrawal syndrome upon discontinuation. In recent years, studies have focused on natural and herbal therapies as alternative sleep aids to overcome the adverse effects of available sleep medications. Plant extracts contain phytochemicals that exert anxiolytic and sedative properties. This includes Passiflora incarnata (FSD-PI) and Lactuca sativa L. (FSD-LS) which can induce sleep. Herein, we assessed the effects of natural products, FSD-PI and FSD-LS, as well as their synergistic effects on pentobarbital sleep-induced ICR mice. We observed that natural extracts did not cause any behavioral changes capable of negative effects in mice. Furthermore, sleep duration was prolonged in pentobarbital-treated mice administered with FSD-LS (100 mg/kg). Our data suggest that FSD-LS may be a safe and effective sleep promoter.
ABSTRACT
Objectives@#The purpose is to investigate personality characteristics according to reports of suicide risk among students in the 2nd step evaluation of the Student Emotional Behavior Test conducted in one district of Daegu in 2022. @*Methods@#A total of 99 students’ school level, gender, and rate of suicide risk reporting were investigated, and sub-factors of Personality Assessment Inventory-Adolescent (PAI-A) were compared according to suicide risk reporting. We also analyzed the factors that have the most significant influence on suicide risk reporting among PAI-A. @*Results@#There was no gender difference in suicide risk reporting, but there was a significant difference at the school level. Among the PAI-A clinical scales, significant differences between groups were found in somatic complaints (SOM), anxiety (ANX), anxiety-related disorder (ADR), depression (DEP), paranoia (PAR), borderline features (BOR), suicide ideation (SUI), nonsupport (NON) and treatment rejection (RXR). Suicide risk reporting was higher in high school students than middle school, and students with high scores of NON on the PAI-A. @*Conclusions@#Reports of suicide risk show differences in internalization factors of personality traits. This means that adolescents are more likely to report suicide risk as they frequently experience inherent negative emotions such as depression and anxiety or as their interpersonal relationships become strained. In addition, it can be said that identifying social networks and forming support resources are important factors in preventing self-harming or suicidal ideation that occur during early adolescence.
ABSTRACT
The mentalis muscle is a paired muscle originating from the alveolar bone of the mandible. This muscle is the main target muscle for botulinum neurotoxin (BoNT) injection therapy, which aims to treat cobblestone chin caused by mentalis hyperactivity. However, a lack of knowledge on the anatomy of the mentalis muscle and the properties of BoNT can lead to side effects, such as mouth closure insufficiency and smile asymmetry due to ptosis of the lower lip after BoNT injection procedures. Therefore, we have reviewed the anatomical properties associated with BoNT injection into the mentalis muscle.An up-to-date understanding of the localization of the BoNT injection point according to mandibular anatomy leads to better injection localization into the mentalis muscle. Optimal injection sites have been provided for the mentalis muscle and a proper injection technique has been described. We have suggested optimal injection sites based on the external anatomical landmarks of the mandible. The aim of these guidelines is to maximize the effects of BoNT therapy by minimizing the deleterious effects, which can be very useful in clinical settings.
ABSTRACT
The depressor anguli oris (DAO) muscle is a thin, superficial muscle located below the corner of the mouth. It is the target for botulinum neurotoxin (BoNT) injection therapy, aimed at treating drooping mouth corners. Hyperactivity of the DAO muscle can lead to a sad, tired, or angry appearance in some patients. However, it is difficult to inject BoNT into the DAO muscle because its medial border overlaps with the depressor labii inferioris and its lateral border is adjacent to the risorius, zygomaticus major, and platysma muscles. Moreover, a lack of knowledge of the anatomy of the DAO muscle and the properties of BoNT can lead to side effects, such as asymmetrical smiles. Anatomical-based injection sites were provided for the DAO muscle, and the proper injection technique was reviewed. We proposed optimal injection sites based on the external anatomical landmarks of the face. The aim of these guidelines is to standardize the procedure and maximize the effects of BoNT injections while minimizing adverse events, all by reducing the dose unit and injection points.
ABSTRACT
Purpose@#The strategy of latent tuberculosis infection (LTBI) treatment in household tuberculosis (TB) contacts has been expanding in South Korea. However, there is little evidence of the cost-effectiveness of LTBI treatment in patients over 35 years of age. This study aimed to evaluate the cost-effectiveness of LTBI treatment among household TB contacts in different age groups in South Korea. @*Materials and Methods@#An age-structured model of TB was developed based on the reports from the Korea Disease Control and Prevention Agency and the National Health Insurance Service. Quality-adjusted life-years (QALY) and the averted number of TBrelated deaths were estimated along with discounted costs for a measure of incremental cost-effectiveness ratios. @*Results@#The number of cumulative active TB cases would decrease by 1564 and 7450 under the scenario of LTBI treatment for those aged <35 years and <70 years, respectively, relative to the no-treatment scenario. The treatment strategies for patients aged 0 to <35 years, <55 years, <65 years, and <70 years would add 397, 1482, 3782, and 8491 QALYs at a cost of $660, $5930, $4560, and $2530, respectively, per QALY. For the averted TB-related deaths, LTBI treatment targeting those aged 0 to <35 years, <55 years, <65 years, and <70 years would avert 7, 89, 155, and 186 deaths at a cost of $35900, $99200, $111100, and $115700 per deaths, respectively, in 20 years. @*Conclusion@#The age-specific expansion policy of LTBI treatment not only for those under 35 years of age but also for those under 65 years of age among household contacts was cost-effective in terms of QALYs and averted TB deaths.
ABSTRACT
Background@#Effective treatment of fluoroquinolone-resistant multidrug-resistant tuberculosis (FQr-MDR-TB) is difficult because of the limited number of available core anti-TB drugs and high rates of resistance to anti-TB drugs other than FQs. However, few studies have examined anti-TB drugs that are effective in treating patients with FQr-MDR-TB in a real-world setting. @*Methods@#The impact of anti-TB drug use on treatment outcomes in patients with pulmonary FQr-MDR-TB was retrospectively evaluated using a nationwide integrated TB database (Korean Tuberculosis and Post-Tuberculosis). Data from 2011 to 2017 were included. @*Results@#The study population consisted of 1,082 patients with FQr-MDR-TB. The overall treatment outcomes were as follows: treatment success (69.7%), death (13.7%), lost to follow-up or not evaluated (12.8%), and treatment failure (3.9%). On a propensity-score-matched multivariate logistic regression analysis, the use of bedaquiline (BDQ), linezolid (LZD), levofloxacin (LFX), cycloserine (CS), ethambutol (EMB), pyrazinamide, kanamycin (KM), prothionamide (PTO), and para-aminosalicylic acid against susceptible strains increased the treatment success rate (vs. unfavorable outcomes). The use of LFX, CS, EMB, and PTO against susceptible strains decreased the mortality (vs. treatment success). @*Conclusion@#A therapeutic regimen guided by drug-susceptibility testing can improve the treatment of patients with pulmonary FQr-MDR-TB. In addition to core anti-TB drugs, such as BDQ and LZD, treatment of susceptible strains with later-generation FQs and KM may be beneficial for FQr-MDR-TB patients with limited treatment options.
ABSTRACT
Inherited bone marrow failure syndrome (IBMFS) is a group of clinically heterogeneous disorders characterized by significant hematological cytopenias of one or more hematopoietic cell lineages and is associated with an increased risk of cancer. The genetic etiology of IBMFS includes germline mutations impacting several key biological processes, such as DNA repair, telomere biology, and ribosome biogenesis, which may cause four major syndromes: Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome. Although the clinical features of some patients may be typical of a particular IBMFS, overlapping and atypical clinical manifestations and variable penetrance pose diagnostic challenges. Here, we review the clinical and genetic features of the major forms of IBMFS and discuss their molecular genetic diagnosis. Next-generation sequencing-based gene panel testing or whole exome sequencing will help elucidate the genetic causes and underlying mechanisms of this genetically heterogeneous group of diseases.
ABSTRACT
Previous reports have demonstrated that genetic mechanisms greatly mediate responses to drugs of abuse, including methamphetamine (METH). The circadian gene Period 2 (Per2 ) has been previously associated with differential responses towards METH in mice. While the behavioral consequences of eliminating Per2 have been illustrated previously, Per2 overexpression has not yet been comprehensively described; although, Per2 -overexpressing (Per2 OE) mice previously showed reduced sensitivity towards METH-induced addiction-like behaviors. To further elucidate this distinct behavior of Per2 OE mice to METH, we identified possible candidate biomarkers by determining striatal differentially expressed genes (DEGs) in both drug-naïve and METH-treated Per2 OE mice relative to wild-type (WT), through RNA sequencing. Of the several DEGs in drug naïve Per2 OE mice, we identified six genes that were altered after repeated METH treatment in WT mice, but not in Per2 OE mice. These results, validated by quantitative real-time polymerase chain reaction, could suggest that the identified DEGs might underlie the previously reported weaker METH-induced responses of Per2 OE mice compared to WT. Gene network analysis also revealed that Asic3, Hba-a1, and Rnf17 are possibly associated with Per2 through physical interactions and predicted correlations, and might potentially participate in addiction. Inhibiting the functional protein of Asic3 prior to METH administration resulted in the partial reduction of METH-induced conditioned place preference in WT mice, supporting a possible involvement of Asic3 in METH-induced reward.Although encouraging further investigations, our findings suggest that these DEGs, including Asic3, may play significant roles in the lower sensitivity of Per2 OE mice to METH.
ABSTRACT
no abstract available.
ABSTRACT
Purpose@#Neuroinflammation is considered an important pathway associated with several diseases that result in cognitive decline. 18F-THK5351 positron emission tomography (PET) signals might indicate the presence of neuroinflammation, as well as Alzheimer’s disease-type tau aggregates. β-amyloid (Aβ)-negative (Aβ–) amnestic mild cognitive impairment (aMCI) may be associated with non-Alzheimer’s disease pathophysiology. Accordingly, we investigated associations between 18F-THK5351 PET positivity and cognitive decline among Aβ– aMCI patients. @*Materials and Methods@#The present study included 25 amyloid PET negative aMCI patients who underwent a minimum of two follow-up neuropsychological evaluations, including clinical dementia rating-sum of boxes (CDR-SOB). The patients were classified into two groups: 18F-THK5351-positive and -negative groups. The present study used a linear mixed effects model to estimate the effects of 18F-THK5351 PET positivity on cognitive prognosis among Aβ– aMCI patients. @*Results@#Among the 25 Aβ– aMCI patients, 10 (40.0%) were 18F-THK5351 positive. The patients in the 18F-THK5351-positive group were older than those in the 18F-THK5351-negative group (77.4±2.2 years vs. 70.0±5.5 years; p<0.001). There was no difference between the two groups with regard to the proportion of apolipoprotein E ε4 carriers. Interestingly, however, the CDR-SOB scores of the 18F-THK5351-positive group deteriorated at a faster rate than those of the 18F-THK5351-negative group (B=0.003, p=0.033). @*Conclusion@#The results of the present study suggest that increased 18F-THK5351 uptake might be a useful predictor of poor prognosis among Aβ– aMCI patients, which might be associated with increased neuroinflammation (ClinicalTrials.gov NCT02656498).
ABSTRACT
Objective@#The primary objective of this study was to investigate the effect of methylphenidate (MPH) on height, weight, and body mass index (BMI) in drug-naive children and adolescents with attention deficit hyperactivity disorder (ADHD) over 24 months. The secondary objective was to investigate whether the age of MPH initiation and sex act as risk factors for growth retardation. @*Methods@#A total of 82 patients with ADHD were included. Weight, height, and BMI were measured at baseline and every 6 months up to 24 months. Weight, height, and BMI data were converted to z-scores and analyzed using two-way repeated-measures ANOVA and multiple linear regression. @*Results@#The z-score of height, weight and BMI decreased from the baseline values. The z-scores of height were at baseline 0.002; 6 months -0.100; 12 months -0.159; 18 months -0.159; 24 months -0.186. The z-scores of weight were at baseline 0.104; 6 months -0.155; 12 months -0.256; 18 months -0.278; 24 months -0.301. Here were no age and sex differences of height, weight, and BMI. @*Conclusion@#The use of MPH was associated with attenuation of weight and height gain rates in children and adolescents with ADHD.
ABSTRACT
Staphylococcus aureus (S. aureus ) is known to induce apoptosis of host immune cells and impair phagocytic clearance, thereby being pivotal in the pathogenesis of atopic dermatitis (AD). Adipose-derived stem cells (ASCs) exert therapeutic effects against inflammatory and immune diseases. In the present study, we investigated whether systemic administration of ASCs restores the phagocytic activity of peripheral blood mononuclear cells (PBMCs) and decolonizes cutaneous S.aureus under AD conditions. AD was induced by injecting capsaicin into neonatal rat pups. ASCs were extracted from the subcutaneous adipose tissues of naïve rats and administered to AD rats once a week for a month. Systemic administration of ASCs ameliorated AD-like symptoms, such as dermatitis scores, serum IgE, IFN-γ+/IL-4+ cell ratio, and skin colonization by S. aureus in AD rats. Increased FasL mRNA and annexin V+/7-AAD+ cells in the PBMCs obtained from AD rats were drastically reversed when co-cultured with ASCs. In contrast, both PBMCs and CD163+ cells bearing fluorescent zymosan particles significantly increased in AD rats treated with ASCs. Additionally, the administration of ASCs led to an increase in the mRNA levels of antimicrobial peptides, such as cathelicidin and β-defensin, in the skin of AD rats. Our results demonstrate that systemic administration of ASCs led to decolonization of S. aureus by attenuating apoptosis of immune cells in addition to restoring phagocytic activity. This contributes to the improvement of skin conditions in AD rats. Therefore, administration of ASCs may be helpful in the treatment of patients with intractable AD.
ABSTRACT
HemoHIM was used as a Korean traditional medicine for anti-inflammatory and antioxidant effects. However, there is no study on the effect of HemoHIM on fatigue. We examined the potential use of HemoHIM to determine whether it can induce anti-fatigue effects. Mice were administered with HemoHIM and VEH for 14 days. On the last day of treatment, mice were subjected to behavioral tests. Subsequently, their plasma and muscle were collected after the treadmill test to measure lactate, lactate dehydrogenase (LDH), ammonia, corticosterone, glycogen, and creatine kinase (CK). We found that HemoHIM moderately increased the running time (s) in the treadmill and mobility duration in the cold swimming tests. In addition, the VEH group showed a significant increase in lactate, LDH, and corticosterone levels in the plasma compared to the group that did not perform the test. However, this was moderately reduced in HemoHIM treatment. Moreover, the HemoHIMtreated group showed significant differences in LDH and glycogen levels, and showed significantly different CK levels in the muscle. HemoHIM is considered to be effective in improving fatigue, given the duration of cold swimming or running time on a treadmill. Also, HemoHIM treatment resulted in reduced concentrations of blood and muscle parameter analysis.
ABSTRACT
Uterine cervical cancer is one of the most common malignancies of the female genital tract.Most recurrent cases of uterine cervical cancer are diagnosed within two years after primary treatment, and late recurrence after a disease-free interval of more than five years is rare. In addition, peritoneal metastases usually present as multifocal discrete nodules in the peritoneal cavity with nodular or diffuse peritoneal thickening. Herein, we report an extremely rare case of late recurrent cervical cancer peritoneal metastasis with an unusual manifestation of a large, solitary necrotic mass in the right subphrenic space on contrast-enhanced CT.
ABSTRACT
Background@#and Purpose Oral administration of cholinesterase inhibitors is often associated with adverse gastrointestinal effects, and so developing an alternative administration route, such as transdermal, is urgently needed. The primary objective of this study was to determine the efficacy and safety of the IPI-301 donepezil transdermal patch compared with donepezil tablets (control) in mild-to-moderate probable Alzheimer’s disease (AD). @*Methods@#This prospective, randomized, double-blind, double-dummy, two-arm parallel, multicenter trial included 399 patients, among whom 303 completed the trial. For randomization, the patients were stratified based on previous treatment and donepezil dose; patients in each stratum were randomized to the test and control groups at a 1:1 ratio. @*Results@#The difference between the control group and the IPI-301 group, quantified as the Hodges–Lehmann estimate of location shift, was 0.00 (95% confidence interval: -1.00 to 1.33), with an upper limit of less than 2.02. The change in Alzheimer’s Disease Cooperative Study– Activities of Daily Living (ADCS-ADL) score differed significantly between the IPI-301 and control groups (p=0.02). However, the changes in the full-itemized ADCS-ADL scores at week 24 did not differ significantly between the two groups. There were no differences between the two groups regarding the scores for the Clinician Interview-Based Impression of Change (f0.9097), Mini-Mental State Examination (p=0.7018), Neuropsychiatric Inventory (p=0.7656), or Clinical Dementia Rating (p=0.9990). Adverse events, vital signs, and laboratory test results were comparable between the two groups. @*Conclusions@#IPI-301 was safe and efficacious in improving cognitive function in patients with mild-to-moderate AD.
ABSTRACT
Neurodevelopmental disorders are complex conditions that pose difficulty in the modulation of proper motor, sensory and cognitive function due to dysregulated neuronal development. Previous studies have reported that an imbalance in the excitation/ inhibition (E/I) in the brain regulated by glutamatergic and/or GABAergic neurotransmission can cause neurodevelopmental and neuropsychiatric behavioral deficits such as autism spectrum disorder (ASD). NMDA acts as an agonist at the NMDA receptor and imitates the action of the glutamate on that receptor. NMDA however, unlike glutamate, only binds to and regulates the NMDA receptor subtypes and not the other glutamate receptors. This study seeks to determine whether NMDA administration in mice i.e., over-activation of the NMDA system would result in long-lasting behavioral deficits in the adolescent mice. Both gender mice were treated with NMDA or saline at early postnatal developmental period with significant synaptogenesis and synaptic maturation. On postnatal day 28, various behavioral experiments were conducted to assess and identify behavioral characteristics. NMDAtreated mice show social deficits, and repetitive behavior in both gender mice at adolescent periods. However, only the male mice but not female mice showed increased locomotor activity. This study implies that neonatal exposure to NMDA may illicit behavioral features similar to ASD. This study also confirms the validity of the E/I imbalance theory of ASD and that NMDA injection can be used as a pharmacologic model for ASD. Future studies may explore the mechanism behind the gender difference in locomotor activity as well as the human relevance and therapeutic significance of the present findings.