Nationwide Treatment Outcomes of Patients With Multidrug/RifampinResistant Tuberculosis in Korea, 2011–2017: A Retrospective Cohort Study (Korean TB-POST)

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.

Guideline for the Surgical Management of Locally Invasive Differentiated Thyroid Cancer From the Korean Society of Head and Neck Surgery

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.

4-F-PCP, a Novel PCP Analog Ameliorates the Depressive-Like Behavior of Chronic Social Defeat Stress Mice via NMDA Receptor Antagonism

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

Effects of Aging and Gender on the Anorectal Function of Healthy Subjects Assessed with Conventional Anorectal Manometry / 대한소화기학회지

Background/Aims@#Anorectal functions are influenced by gender and age. This study sought to define the normal anorectal pressure values measured with conventional anorectal manometry (ARM) and to evaluate the effects of age and gender on anorectal function in asymptomatic subjects. @*Methods@#Conventional ARM was used to measure the anorectal pressures of 164 asymptomatic healthy subjects, including 86 males and 76 females. @*Results@#The resting anal pressures of males and females aged >60 years were significantly lower than those ≤60 years (males, 44.09±14.22 vs. 57.45±17.69, p<0.001; females, 44.09±14.22 vs. 57.45±17.69, p<0.001). The anal high-pressure zone was significantly lower in older males than in younger males (2.42±0.93 vs. 2.82±0.739, p=0.048). In both age groups (<60 and ≥60 years), the anal squeezing pressures of males were significantly higher than those of females (<60 years old, 168.40±75.94 vs. 119.15±57.53, p=0.001; ≥60 years, 149.61±64.68 vs. 101.3±54.92, p=0.006). @*Conclusions@#The normal anorectal pressure values measured with ARM in males and females were different. Older males and females had lower anal resting pressures than those of the younger subjects, but squeezing pressure was not affected by age.

Clinical Practice Guideline for Dementia (Diagnosis and Evaluation):2021 Revised Edition

no abstract available.

Adipose-derived stem cells decolonize skin Staphylococcus aureus by enhancing phagocytic activity of peripheral blood mononuclear cells in the atopic rats

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.

Standardized Extract (HemoHIM) Ameliorated High Intensity Exercise Induced Fatigue in Mice

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.

Unusual Peritoneal Metastasis of Late Recurrent Uterine Cervical Cancer: A Case Report and Literature Review

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.

A Multinational, Multicenter, Randomized, Double-Blind, Active Comparator, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Donepezil Transdermal Patch in Patients With Alzheimer’s Disease

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.

Behavioral Deficits in Adolescent Mice after Sub-Chronic Administration of NMDA during Early Stage of Postnatal Development

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.

18F-THK5351 PET Positivity and Longitudinal Changes in Cognitive Function in β-Amyloid-Negative Amnestic Mild Cognitive Impairment

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).

A 24-Month Effects of Methylphenidate Use on Growth in Children and Adolescents With Attention Deficit Hyperactivity Disorder

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.

Genetics and genomics of bone marrow failure syndrome

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.

Differentially Expressed Genes in Period 2-Overexpressing Mice Striatum May Underlie Their Lower Sensitivity to Methamphetamine Addiction-Like Behavior

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.

Localizing the nerve to the mylohyoid using the mylohyoid triangle / 대한해부학회지

The nerve to the mylohyoid muscle has been well studied but there are no specific anatomical landmarks for identifying it. Therefore, we aimed to identify anatomical landmarks for localizing the nerve to the mylohyoid muscle in the submandibular region. Sixteen sides from eight embalmed Caucasian cadaveric heads were used in this study. The mean age at the time of death of the specimens was 80.3 years. The anterior and posterior bellies of the digastric muscle, submental artery, and mylohyoid muscle were dissected to verify their relationships with the nerve to the mylohyoid muscle. The nerve to the mylohyoid muscle was found medial to the submental artery, lateral to the anterior belly of the digastric muscle, and anterior to the posterior border of the mylohyoid muscle on all sides. Herein, we identified what we term the mylohyoid triangle. This anatomical region can help localize the nerve to the mylohyoid muscle.

Body donation trends in Yonsei University: a statistical analysis of donor records / 대한해부학회지

Body donation trends in Korea have changed significantly over the last 3 decades. Establishing a body donation system will promote donations to universities for academic purposes. Yonsei University College of Medicine started its own body donation system in 1992, including documenting donors’ records. However, there has been no reported attempt to analyze the trend of these records, which could provide noteworthy information that can be interpreted for medical advances. This study performed a statistical analysis of the donors’ records between 1992 and 2019 to analyze the sociological and anthropological changes. Donor personal information such as sex, age, religion, and place and cause of death were extracted from the Yonsei University College of Medicine database. Our statistical analysis revealed significant correlations between donors’ records and the changes in the number of geriatric hospitals, religious beliefs, number of donations, and donor age.

Impact of non-hepatic hyperammonemia on mortality in intensive care unit patients: a retrospective cohort study

Background/Aims@#The effect of hyperammonemia on the mortality in patients with liver cirrhosis is well documented. However, little is known about the impact of hyperammonemia on mortality among intensive care unit patients without hepatic disease. We aimed to investigate factors associated with non-hepatic hyperammonemia among intensive care unit patients and to evaluate the factors related to the 7- and 90-day mortality. @*Methods@#Between February 2016 and February 2020, 948 patients without hepatic disease who had 972 episodes of admission to the intensive care unit were retrospectively enrolled and classified as hyperammonemia grades 0 (≤ 80 µg/dL; 585 [60.2%]), 1 (≤ 160 µg/dL; 291 [29.9%]), 2 (≤ 240 µg/dL; 55 [5.7%]), and 3 (> 240 µg/dL; 41 [4.2%]). Factors associated with hyperammonemia and the 7- and 90-day mortality were evaluated by multivariate logistic regression analysis and Cox regression analysis, respectively. Kaplan-Meier survival curves for the 7- and 90-day mortality were constructed. @*Results@#The independent risk factors for hyperammonemia were male sex (odds ratio, 1.517), age (0.984/year), acute brain failure (2.467), acute kidney injury (1.437), prothrombin time-international normalized ratio (2.272/unit), and albumin (0.694/g/dL). The 90-day mortality rate in the entire cohort was 24.3% and gradually increased with increasing hyperammonemia grade at admission (17.9%, 28.2%, 43.6%, and 61.0% in patients with grades 0, 1, 2, and 3, respectively). Additionally, non-hepatic hyperammonemia was an independent predictor of the 90- day mortality in intensive care unit patients. @*Conclusions@#Non-hepatic hyperammonemia is common (39.8%) and associated with the 90-day mortality among intensive care unit patients.

Factors Associated With Dementia Knowledge and Dementia Worry in the South Korean Elderly Population

Objective@#South Korea is one of the countries with a very fast aging rate, and the prevalence of dementia is rapidly increasing. However, there are relatively few studies pertaining to sociodemographic and physical health-related factors associated with dementia knowledge and dementia worry. @*Methods@#This was a cross-sectional survey of a community in Seocho-gu, Seoul, Republic of Korea. Overall, 1,869 adults aged 60 years participated. Participants completed an online interview or face-to-face interview. Survey data comprised self-report questions including dementia knowledge, dementia worry, demographic, psychological, exercise, and cognitive activities. We conducted logistic regression analysis. @*Results@#There was a significant positive association between dementia worry and knowledge. Family history of dementia, education, income, sleep problems, depressed mood and loss of volition, chronic diseases, and presence of a past job were associated with dementia knowledge or worry. Reading, art, or social cognitive activities had a significant positive association with dementia knowledge, and writing or musical cognitive activities had a negative association with dementia worry. @*Conclusion@#We found that people with more dementia knowledge and less dementia worry engaged more in cognitive activities that could prevent dementia. Public education should be planned to improve dementia knowledge and reduce dementia worry.

Anatomic Description of the Infraorbital Soft Tissues by Three-dimensional Scanning System

Purpose@#For minimally invasive procedures, three-dimensional (3D) anatomical knowledge of the structures of the face is essential. This study aimed to describe the thickness of the skin and subcutaneous tissue and depths of the facial muscles located in the infraorbital region using a 3D scanner to provide critical clinical anatomical guidelines for improving minimally invasive cosmetic procedures. @*Materials and Methods@#The 3D scanning images of 38 Korean cadavers (22 males and 16 females; age range: 51~94 years at the time of death) were analyzed. Eight facial landmarks (P1~P8) were marked on the cadaveric faces. The images were scanned in three steps–undissected face, hemiface after skinning, and revealing the facial muscles. Student’s t-test was used to identify significant differences.Result: The skin and subcutaneous tissue tended to become thicker from the upper to lower and medial to lateral aspects, and the muscles followed the same pattern as that of the most superficial located muscle and the deepest located muscles. No significant sex-related differences were found in the skin at any landmark. However, the muscles tended to be deeper in the female participants. @*Conclusion@#The study data can serve as a basis for creating or enhancing clinical anatomy-based guidelines or improving procedures in the infraorbital region.

The Effects of College Students’ Dual Use of Electronic Cigarette and Conventional Cigarette on Depression

Purpose@#This study was conducted to find out the association between dual-use of the electronic cigarette (EC) and conventional cigarette (CC) and depression among undergraduate students. Methods: The participants of this study were 225 undergraduate students who were attending two universities located in Ulsan metropolitan city. Descriptive statistics and multiple regression were conducted to analyze the data. @*Results@#Nicotine dependence and depression were significantly higher in the dual-use group than in the single-use group. Dual-use of the EC and CC was significantly associated with depression among undergraduate students. In addition, quality of sleep was significantly associated with depression among undergraduate students. @*Conclusion@#In order to prevent depression among undergraduate students, it is necessary to improve the awareness of the danger of dual use of the EC and CC.