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1.
J Korean Med Sci ; 39(24): e189, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38915281

ABSTRACT

BACKGROUND: Antimicrobial resistance (AMR) is an important global public health concern in adults and children. Laryngotracheobronchitis (croup) is a common acute respiratory infection (ARI) among children, most often caused by a virus, and should not be treated with antibiotics. Reducing the usage of unnecessary antibiotics in ARI using an antimicrobial stewardship program (ASP) is an effective measure against AMR in children. This study investigates the antibiotic prescription pattern in pediatric patients with laryngotracheobronchitis in Korea. Our results will be useful to improve the ASP. METHODS: The data were obtained from the government agency Health Insurance Review and Assessment Service. We analyzed outpatient prescriptions issued to children ≤ 5 years of age with a first-listed diagnosis code for laryngotracheobronchitis, i.e., International Classification of Disease, 10th Revision, code J050 (croup), J040 (laryngitis), or J041 (tracheitis), during 2017-2020. For each prescription, demographic information and information about medical facilities visited (type of hospital, specialty of physician, location of hospital) were extracted. The overall antibiotic prescription rate was subsequently estimated, and multivariable analysis was conducted to determine the associated factors of antibiotic prescription. Prescribed antibiotics were described and classified into extended-spectrum penicillins, cephalosporin, and macrolides. RESULTS: Of 2,358,194 prescriptions reviewed, 829,172 (35.2%) contained antibiotics. In the multivariable analysis, management in a hospital was the strongest factor associated with antibiotic prescription (adjusted odds ratio [aOR], 22.33; 95% confidence interval [CI], 20.87-23.89; P < 0.001), followed by management in a clinic (aOR, 12.66; 95% CI, 11.83-13.54; P < 0.001) and management in a general hospital (aOR, 8.96; 95% CI, 8.37-9.59; P < 0.001). Antibiotic prescription was also significantly associated with patients who were ≤ 2 years of age, managed by a pediatric specialist, and treated at a hospital located in a non-metropolitan region. Overall, extended-spectrum penicillins were the most frequently prescribed (18.6%) antibiotics, followed by cephalosporins (9.4%) and macrolides (8.5%). CONCLUSION: The results of our study suggest that ASPs need to focus on physicians in hospitals, clinics, general hospitals, and pediatric specialties. Providing education programs to these groups to increase awareness of AMR and appropriate antibiotics use could be effective ASP policy and may help to reduce unnecessary prescriptions of antibiotics for laryngotracheobronchitis among pediatric patients and therefore potentially AMR in children in Korea.


Subject(s)
Anti-Bacterial Agents , Antimicrobial Stewardship , Tracheitis , Humans , Anti-Bacterial Agents/therapeutic use , Republic of Korea , Child, Preschool , Infant , Male , Female , Tracheitis/drug therapy , Laryngitis/drug therapy , Practice Patterns, Physicians'/statistics & numerical data , Bronchitis/drug therapy , Infant, Newborn , Drug Prescriptions/statistics & numerical data , Croup/drug therapy
2.
Turk Neurosurg ; 34(4): 701-707, 2024.
Article in English | MEDLINE | ID: mdl-38874252

ABSTRACT

AIM: To share our clinical insights into octogenarian patients with unruptured intracranial aneurysms (UIAs) and evaluate the treatment strategies for this demographic. MATERIAL AND METHODS: A retrospective analysis was conducted on data from 134 patients with a follow-up exceeding 6 months, all enrolled in this study. We assessed the incidence rates (IRs) of aneurysm growth and rupture, along with potential predictors of aneurysm growth. RESULTS: Among the 134 patients, 99 (73.9%) underwent conservative management, 25 (18.7%) received coiling, and 10 (7.5%) underwent clipping. The mean age of the cohort was 81.8 years. The middle cerebral artery was the most common location for aneurysms. The mean aneurysm size was 4.9 mm, with sizes significantly larger in the treatment groups (coiling and clipping) compared to the observation group (4.4 mm in the observation group; 5.9 and 7.4 mm in the coiling and clipping groups, respectively). The proportion of aneurysms with a daughter sac was higher in the treatment groups compared to the observation group (6.1% vs. 44% [coiling] and 50% [clipping]). The IR of aneurysm growth was 5.9 per 100 person-years, and that of aneurysm rupture was 0.8 per 100 person-years. No factors were statistically significant for aneurysm growth. CONCLUSION: Age alone, especially in individuals over 80 years old, may not be a contraindication for UIA treatment. We recommend considering treatment in octogenarians with high-risk aneurysm features, such as a large aneurysm and the presence of a daughter sac, as the complication rates are low.


Subject(s)
Aneurysm, Ruptured , Intracranial Aneurysm , Humans , Intracranial Aneurysm/therapy , Intracranial Aneurysm/surgery , Female , Male , Retrospective Studies , Aged, 80 and over , Aneurysm, Ruptured/surgery , Treatment Outcome , Neurosurgical Procedures/methods , Embolization, Therapeutic/methods , Endovascular Procedures/methods
3.
RSC Adv ; 14(25): 18064-18072, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38841393

ABSTRACT

Thermoset epoxy resins are widely used in research and commercial applications. Zeolite imidazole framework-8 (ZIF-8), graphitic carbon nitride (GCN, g-C3N4), and S-doped graphitic carbon nitride (SCN, S-g-C3N4) composites were synthesized as accelerators and their effects on the physical properties of epoxies were examined. An ultrasound-assisted method was used to prepare ZIF-8/GCN and ZIF-8/SCN nanocomposites while g-C3N4 and S-g-C3N4 were prepared from the calcination of melamine and thiourea, respectively. The surface morphology, and particle size were characterized by scanning electron microscopy, and X-ray diffraction. The properties of synthesized nanocomposites were measured using Fourier-transform infrared spectroscopy. After the accelerator was added to the epoxy composites, their activation energies were calculated using differential scanning calorimetry. The tensile strength and flexural strength were measured using a universal testing machine and impact strength was measured by using an Izod impact strength tester. The impact strength of ZIF-8/SCN nanocomposites was enhanced by 45.2%. The storage stability of the epoxy compositions with different catalysts was evaluated by measuring the variation of viscosity with time at a constant temperature.

4.
Neurosurg Rev ; 47(1): 259, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38844722

ABSTRACT

raumatic brain injury (TBI) is a significant global health concern, particularly affecting young individuals, and is a leading cause of mortality and morbidity worldwide. Despite improvements in treatment infrastructure, many TBI patients choose discharge against medical advice (DAMA), often declining necessary surgical interventions. We aimed to investigate the factors that can be associated with DAMA in TBI patients that were recommended to have surgical treatment. This study was conducted at single tertiary university center (2008-2018), by retrospectively reviewing 1510 TBI patients whom visited the emergency room. We analyzed 219 TBI surgical candidates, including 50 declining surgery (refused group) and the others whom agreed and underwent decompressive surgery. Retrospective analysis covered demographic characteristics, medical history, insurance types, laboratory results, CT scan findings, and GCS scores. Statistical analyses identified factors influencing DAMA. Among surgical candidates, 169 underwent surgery, while 50 declined. Age (60.8 ± 17.5 vs. 70.5 ± 13.8 years; p < 0.001), use of anticoagulating medication (p = 0.015), and initial GCS scores (9.0 ± 4.3 vs. 5.3 ± 3.2; p < 0.001) appeared to be associated with refusal of decompressive surgery. Based on our analysis, factors influencing DAMA for decompressive surgery included age, anticoagulant use, and initial GCS scores. Contrary to general expectations and some previous studies, our analysis revealed that the patients' medical conditions had a larger impact than socioeconomic status under the Korean insurance system, which fully covers treatment for TBI. This finding provides new insights into the factors affecting DAMA and could be valuable for future administrative plans involving national insurance.


Subject(s)
Brain Injuries, Traumatic , Patient Discharge , Humans , Brain Injuries, Traumatic/surgery , Male , Female , Middle Aged , Aged , Adult , Retrospective Studies , Aged, 80 and over , Decompressive Craniectomy , Treatment Refusal , Decompression, Surgical , Glasgow Coma Scale
5.
J Neurophysiol ; 131(6): 1240-1249, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38691013

ABSTRACT

Although many patients with mild traumatic brain injury (mTBI) suffer from postconcussional syndrome (PCS) including abnormal emotional responses, most conventional imaging studies fail to detect any causative brain lesion. We hypothesized that event-related electroencephalography (EEG) recordings with time-frequency analysis would show a distinguishable pattern in patients with mTBI with PCS compared with normal healthy controls. EEG signals were collected from a total of 18 subjects: eight patients with mTBI with PCS and 10 healthy control subjects. The signals were recorded while the subjects were presented with affective visual stimuli, including neutral, pleasant, and unpleasant emotional cues. Event-related spectral perturbation analysis was performed to calculate frontal midline theta activity and posterior midline gamma activity, followed by statistical analysis to identify whether patients with mTBI with PCS have distinct patterns of theta or gamma oscillations in response to affective stimuli. Compared with the healthy control group, patients with mTBI with PCS did not show a significant increase in the power of frontal theta activity in response to the pleasant stimuli, indicating less susceptibility toward pleasant cues. Moreover, the patient group showed attenuated gamma oscillatory activity, with no clear alteration in gamma oscillations in response to either pleasant or unpleasant cues. This study demonstrates that patients with mTBI with PCS exhibited altered patterns of oscillatory activities in the theta and gamma bands in response to affective visual stimuli compared with the normal control group. The current finding implicates that these distinguishable patterns of brain oscillation may represent the mechanism behind various psychiatric symptoms in patients with mTBI.NEW & NOTEWORTHY Patients with mild traumatic brain injury (mTBI) with postconcussional syndrome (PCS) exhibited altered patterns of changes in oscillatory activities in the theta and gamma bands in response to visual affective stimuli. Distinguishable patterns of brain oscillation may represent the mechanism behind various psychiatric symptoms in patients with mTBI.


Subject(s)
Gamma Rhythm , Post-Concussion Syndrome , Theta Rhythm , Humans , Gamma Rhythm/physiology , Male , Adult , Female , Theta Rhythm/physiology , Post-Concussion Syndrome/physiopathology , Middle Aged , Photic Stimulation , Emotions/physiology , Young Adult , Visual Perception/physiology , Electroencephalography
6.
Biomed Pharmacother ; 176: 116781, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38805966

ABSTRACT

Influenza A virus causes numerous deaths and infections worldwide annually. Therefore, we have considered nanobodies as a potential treatment for patients with severe cases of influenza. We developed a nanobody that was expected to have protective efficacy against the A/California/04/2009 (CA/04; pandemic 2009 flu strain) and evaluated its therapeutic efficacy against CA/04 in mice experiments. This nanobody was derived from the immunization of the alpaca, and the inactivated CA/04 virus was used as an immunogen. We successfully generated a nanobody library through bio-panning, phage ELISA, and Bio-layer interferometry. Moreover, we confirmed that administering nanobodies after lethal doses of CA/04 reduced viral replication in the lungs and influenza-induced clinical signs in mice. These research findings will help to develop nanobodies as viral therapeutics for CA/04 and other infectious viruses.


Subject(s)
Influenza A Virus, H1N1 Subtype , Orthomyxoviridae Infections , Single-Domain Antibodies , Animals , Single-Domain Antibodies/immunology , Influenza A Virus, H1N1 Subtype/immunology , Mice , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/drug therapy , Orthomyxoviridae Infections/virology , Female , Mice, Inbred BALB C , Camelids, New World/immunology , Lung/immunology , Lung/virology , Lung/drug effects , Lung/pathology , Antibodies, Viral/immunology , Virus Replication/drug effects
7.
Ann Surg Treat Res ; 106(5): 263-273, 2024 May.
Article in English | MEDLINE | ID: mdl-38725802

ABSTRACT

Purpose: The cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is involved in the progression of various cancers, but its biological roles in breast cancer (BRCA) remain unclear. Therefore, we performed a systematic multiomic analysis to expound on the prognostic value and underlying mechanism of CTLA4 in BRCA. Methods: We assessed the effect of CTLA4 expression on BRCA using a variety of bioinformatics platforms, including Oncomine, GEPIA, UALCAN, PrognoScan database, Kaplan-Meier plotter, and R2: Kaplan-Meier scanner. Results: CTLA4 was highly expressed in BRCA tumor tissue compared to normal tissue (P < 0.01). The CTLA4 messenger RNA levels in BRCA based on BRCA subtypes of Luminal, human epidermal growth factor receptor 2, and triple-negative BRCA were considerably higher than in normal tissues (P < 0.001). However, the overexpression of CTLA4 was associated with a better prognosis in BRCA (P < 0.001) and was correlated with clinicopathological characteristics including age, T stage, estrogen receptors, progesterone receptors, and prediction analysis of microarray 50 (P < 0.01). The infiltration of multiple immune cells was associated with increased CTLA4 expression in BRCA (P < 0.001). CTLA4 was highly enriched in antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. Conclusion: This study provides suggestive evidence of the prognostic role of CTLA4 in BRCA, which may be a therapeutic target for BRCA. Furthermore, CTLA4 may influence BRCA prognosis through antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. These findings help us understand how CTLA4 plays a role in BRCA and set the stage for more research.

8.
J Wildl Dis ; 60(3): 779-782, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38688514

ABSTRACT

A free-living female Korean water deer (Hydropotes inermis argyropus) was found with swelling in the left femur. Radiographic and histopathologic examination confirmed distal femoral osteosarcoma with metastases to the inguinal lymph node and the lungs; there are no previous reports of osteosarcoma in water deer.


Subject(s)
Deer , Osteosarcoma , Animals , Osteosarcoma/veterinary , Osteosarcoma/pathology , Female , Bone Neoplasms/veterinary , Bone Neoplasms/pathology , Lung Neoplasms/veterinary , Lung Neoplasms/secondary , Lung Neoplasms/pathology , Femur/pathology , Femoral Neoplasms/veterinary , Femoral Neoplasms/pathology , Lymphatic Metastasis
9.
Article in English | MEDLINE | ID: mdl-38593432

ABSTRACT

Printing structurally colored patterns is of great importance for providing customized graphics for various purposes. Although a direct writing technique has been developed, the use of colloidal dispersions as photonic inks requires delicate printing conditions and restricts the mechanical and optical properties of printed patterns. In this work, we produce elastic photonic microbeads through scalable bulk emulsification and formulate photonic inks containing microbeads for direct writing. To produce the microbeads, a photocurable colloidal dispersion is emulsified into a highly concentrated sucrose solution via vortexing, which results in spherical emulsion droplets with a relatively narrow size distribution. The microbeads are produced by photopolymerization and are then suspended in urethane acrylate resin at volume fractions of 0.35-0.45. The photonic inks retain high color saturation of the microbeads and offer enhanced printability and dimensional control on various target substrates including fabrics, papers, and even skins. Importantly, the printed graphics show high mechanical stability as the elastic microbeads are embedded in the polyurethane matrix. Moreover, the colors show a wide viewing angle and low-angle dependency due to the optical isotropy of individual microbeads and light refraction at the air-matrix interface. We postulate that this versatile direct writing technique is potentially useful for structural color coating and printing on the surfaces of arbitrary 3D objects.

10.
bioRxiv ; 2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38559035

ABSTRACT

Background: Mitochondrial (Mito) dysfunction in IBD reduces mucosal O2 consumption and increases O2 delivery to the microbiome. Increased enteric O2 promotes blooms of facultative anaerobes (eg. Proteobacteria ) and restricts obligate anaerobes (eg. Firmicutes ). Dysbiotic metabolites negatively affect host metabolism and immunity. Our novel compound (AuPhos) upregulates intestinal epithelial cell (IEC) mito function, attenuates colitis and corrects dysbiosis in humanized Il10-/- mice. We posit that AuPhos corrects IBD-associated dysbiotic metabolism. Methods: Primary effect of AuPhos on mucosal Mito respiration and healing process was studied in ex vivo treated human colonic biopsies and piroxicam-accelerated (Px) Il10-/- mice. Secondary effect on microbiome was tested in DSS-colitis WT B6 and germ-free 129.SvEv WT or Il10-/- mice reconstituted with human IBD stool (Hu- Il10-/- ). Mice were treated orally with AuPhos (10- or 25- mg/kg; q3d) or vehicle, stool samples collected for fecal lipocalin-2 (f-LCN2) assay and microbiome analyses using 16S rRNA sequencing. AuPhos effect on microbial metabolites was determined using untargeted global metabolomics. AuPhos-induced hypoxia in IECs was assessed by Hypoxyprobe-1 staining in sections from pimonidazole HCl-infused DSS-mice. Effect of AuPhos on enteric oxygenation was assessed by E. coli Nissle 1917 WT (aerobic respiration-proficient) and cytochrome oxidase (cydA) mutant (aerobic respiration-deficient). Results: Metagenomic (16S) analysis revealed AuPhos reduced relative abundances of Proteobacteria and increased blooms of Firmicutes in uninflamed B6 WT, DSS-colitis, Hu-WT and Hu- Il10-/- mice. AuPhos also increased hypoxyprobe-1 staining in surface IECs suggesting enhanced O2 utilization. AuPhos-induced anaerobiosis was confirmed by a significant increase in cydA mutant compared to WT (O2-utlizing) E.coli . Ex vivo treatment of human biopsies with AuPhos showed significant increase in Mito mass, and complexes I and IV. Further, gene expression analysis of AuPhos-treated biopsies showed increase in stem cell markers (Lgr4, Lgr5, Lrig1), with concomitant decreases in pro-inflammatory markers (IL1ß,MCP1, RankL). Histological investigation of AuPhos-fed Px- Il10-/- mice showed significantly decreased colitis score in AuPhos-treated Px- Il10-/- mice, with decrease in mRNA of pro-inflammatory cytokines and increase in Mito complexes ( ND5 , ATP6 ). AuPhos significantly altered microbial metabolites associated with SCFA synthesis, FAO, TCA cycle, tryptophan and polyamine biosynthesis pathways. AuPhos increased pyruvate, 4-hydroxybutyrate, 2-hydroxyglutarate and succinate, suggesting an upregulation of pyruvate and glutarate pathways of butyrate production. AuPhos reduced IBD-associated primary bile acids (BA) with concomitant increase in secondary BA (SBA). AuPhos treatment significantly decreased acylcarnitines and increased L-carnitine reflective of enhanced FAO. AuPhos increases TCA cycle intermediates and creatine, energy reservoir substrates indicating enhanced OxPHOS. Besides, AuPhos also upregulates tryptophan metabolism, decreases Kynurenine and its derivatives, and increases polyamine biosynthesis pathway (Putresceine and Spermine). Conclusion: These findings indicate that AuPhos-enhanced IEC mitochondrial function reduces enteric O2 delivery, which corrects disease-associated metabolomics by restoring short-chain fatty acids, SBA, AA and IEC energy metabolism.

11.
Parasitol Res ; 123(4): 192, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38652173

ABSTRACT

The pathogenic free-living amoebae, Naegleria fowleri and Acanthamoeba polyphaga, are found in freshwater, soil, and unchlorinated or minimally chlorinated swimming pools. N. fowleri and A. polyphaga are becoming problematic as water leisure activities and drinking water are sources of infection. Chlorine dioxide (ClO2) gas is a potent disinfectant that is relatively harmless to humans at the concentration used for disinfection. In this study, we examined the amoebicidal effects of ClO2 gas on N. fowleri and A. polyphaga. These amoebae were exposed to ClO2 gas from a ready-to-use product (0.36 ppmv/h) for 12, 24, 36, and 48 h. Microscopic examination showed that the viability of N. fowleri and A. polyphaga was effectively inhibited by treatment with ClO2 gas in a time-dependent manner. The growth of N. fowleri and A. polyphaga exposed to ClO2 gas for 36 h was completely inhibited. In both cases, the mRNA levels of their respective actin genes were significantly reduced following treatment with ClO2 gas. ClO2 gas has an amoebicidal effect on N. fowleri and A. polyphaga. Therefore, ClO2 gas has been proposed as an effective agent for the prevention and control of pathogenic free-living amoeba contamination.


Subject(s)
Acanthamoeba , Chlorine Compounds , Disinfectants , Naegleria fowleri , Oxides , Chlorine Compounds/pharmacology , Naegleria fowleri/drug effects , Acanthamoeba/drug effects , Oxides/pharmacology , Disinfectants/pharmacology , Time Factors , Survival Analysis , Amebicides/pharmacology
12.
Can Vet J ; 65(4): 371-374, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38562972

ABSTRACT

An 8-year-old neutered male shih tzu dog underwent laparotomy for cystolithectomy. Ten days later, multiple various-sized cystic nodules were observed on the suture line and surrounding abdominal skin, although the surgical incision had healed well. Microscopically, various-sized cysts lined with thin walls of stratified squamous epithelium in the dermis were dilated and filled with keratin. Adnexal differentiation from the wall was not seen. Thus, the abdominal lesions were diagnosed as comedones and epidermal cysts. Herein, we describe the case of a dog with comedones and epidermal cysts on the abdominal skin after a laparotomy. Key clinical message: Multiple various-sized cystic lesions of the follicles are described. The implantation of epidermal fragments into the dermis by surgery may induce epidermal cysts and comedones in the skin of hyperadrenocorticism-affected dogs.


Comédons et kystes épidermiques sur la peau abdominale d'un chien survenant après une laparotomie. Un chien shih tzu mâle castré de 8 ans a subi une laparotomie pour cystolithectomie. Dix jours plus tard, de multiples nodules kystiques de différentes tailles ont été observés sur la ligne de suture et sur la peau abdominale environnante, bien que l'incision chirurgicale ait bien cicatrisé. Au microscope, des kystes de différentes tailles bordés de fines parois d'épithélium pavimenteux stratifié dans le derme étaient dilatés et remplis de kératine. Aucune différenciation annexielle par rapport à la paroi n'a été observée. Ainsi, les lésions abdominales ont été diagnostiquées comme des comédons et des kystes épidermiques. Nous décrivons ici le cas d'un chien présentant des comédons et des kystes épidermiques sur la peau abdominale après une laparotomie.Message clinique clé:De multiples lésions kystiques des follicules, de différentes tailles, sont décrites. L'implantation chirurgicale de fragments d'épiderme dans le derme peut provoquer des kystes épidermiques et des comédons dans la peau des chiens atteints d'hypercorticisme.(Traduit par Dr Serge Messier).


Subject(s)
Dog Diseases , Epidermal Cyst , Dogs , Male , Animals , Epidermal Cyst/surgery , Epidermal Cyst/veterinary , Epidermal Cyst/pathology , Laparotomy/veterinary , Dog Diseases/surgery , Dog Diseases/pathology
14.
J Korean Med Sci ; 39(7): e64, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38412611

ABSTRACT

BACKGROUND: The treatment of pediatric patients with latent tuberculosis infection (LTBI) is a crucial TB control strategy. LTBI is not a reportable communicable disease, and data regarding LTBI treatment in pediatric patients in Korea are scarce. This study aimed to investigate the prescription patterns and treatment completion rates among pediatric patients with LTBI in Korea by analyzing National Health reimbursement claims data. METHODS: We retrospectively analyzed outpatient prescription records for pediatric patients aged 18 or younger with LTBI-related diagnostic codes from 2016 to 2020. We compared the frequency of prescriptions for the standard treatment regimen (9 months of isoniazid [9H]) and an alternative treatment regimen (3 months of isoniazid plus rifampicin [3HR]). We also assessed the treatment incompletion rates by age group, treatment regimen, treatment duration, the level of medical facility, physician's specialty, and hospital location. We performed multivariable analysis to identify factors influencing treatment incompletion. RESULTS: Among the 11,362 patients who received LTBI treatment, 6,463 (56.9%) were prescribed the 9H regimen, while 4,899 (43.1%) received the 3HR regimen. Patients in the 3HR group were generally older than those in the 9H group. The proportion of 3HR regimen prescriptions significantly greater in the later period (2018-2020), in primary hospitals, under the management of non-pediatric specialists, and in metropolitan regions. The overall treatment incompletion rate was 39.7% (9H group: 46.9%, 3HR group: 30.3%). In the multivariable analysis, 9H regimen prescription was the strongest factor associated with treatment incompletion (adjusted odds ratio, 2.42; 95% confidence interval, 2.20-2.66; P < 0.001). Additionally, management in a primary hospital, a hospital's location in a non-metropolitan region, and management by a non-pediatric specialist were also significant risk factors for treatment incompletion. CONCLUSION: Our study results suggest that promoting the use of 3HR regimen prescriptions could be an effective strategy to enhance treatment completion. Physicians in primary hospitals, hospitals located in non-metropolitan regions, and physicians without a pediatric specialty require increased attention when administering LTBI treatment to pediatric patients to ensure treatment completion.


Subject(s)
Isoniazid , Latent Tuberculosis , Humans , Child , Isoniazid/therapeutic use , Antitubercular Agents/therapeutic use , Retrospective Studies , Latent Tuberculosis/drug therapy , Latent Tuberculosis/diagnosis , Rifampin/therapeutic use , Outpatients , Republic of Korea
15.
Nat Neurosci ; 27(1): 90-101, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38177337

ABSTRACT

Panic disorder is characterized by uncontrollable fear accompanied by somatic symptoms that distinguish it from other anxiety disorders. Neural mechanisms underlying these unique symptoms are not completely understood. Here, we report that the pituitary adenylate cyclase-activating polypeptide (PACAP)-expressing neurons in the lateral parabrachial nucleus projecting to the dorsal raphe are crucial for panic-like behavioral and physiological alterations. These neurons are activated by panicogenic stimuli but inhibited in conditioned fear and anxiogenic conditions. Activating these neurons elicits strong defensive behaviors and rapid cardiorespiratory increase without creating aversive memory, whereas inhibiting them attenuates panic-associated symptoms. Chemogenetic or pharmacological inhibition of downstream PACAP receptor-expressing dorsal raphe neurons abolishes panic-like symptoms. The pontomesencephalic PACAPergic pathway is therefore a likely mediator of panicogenesis, and may be a promising therapeutic target for treating panic disorder.


Subject(s)
Anxiety , Medically Unexplained Symptoms , Mice , Animals , Pituitary Adenylate Cyclase-Activating Polypeptide/metabolism , Fear , Behavior, Animal/physiology
16.
Dev Cell ; 59(2): 211-227.e5, 2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38141609

ABSTRACT

Fetal bone development occurs through the conversion of avascular cartilage to vascularized bone at the growth plate. This requires coordinated mobilization of osteoblast precursors with blood vessels. In adult bone, vessel-adjacent osteoblast precursors are maintained by mechanical stimuli; however, the mechanisms by which these cells mobilize and respond to mechanical cues during embryonic development are unknown. Here, we show that the mechanoresponsive transcriptional regulators Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) spatially couple osteoblast precursor mobilization to angiogenesis, regulate vascular morphogenesis to control cartilage remodeling, and mediate mechanoregulation of embryonic murine osteogenesis. Mechanistically, YAP and TAZ regulate a subset of osteoblast-lineage cells, identified by single-cell RNA sequencing as vessel-associated osteoblast precursors, which regulate transcriptional programs that direct blood vessel invasion through collagen-integrin interactions and Cxcl12. Functionally, in 3D human cell co-culture, CXCL12 treatment rescues angiogenesis impaired by stromal cell YAP/TAZ depletion. Together, these data establish functions of the vessel-associated osteoblast precursors in bone development.


Subject(s)
Adaptor Proteins, Signal Transducing , Trans-Activators , Animals , Humans , Mice , Adaptor Proteins, Signal Transducing/metabolism , Angiogenesis , Bone Development , Morphogenesis , Osteoblasts/metabolism , Trans-Activators/metabolism , Transcription Factors/metabolism , YAP-Signaling Proteins
17.
Biomed Pharmacother ; 170: 116010, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38128183

ABSTRACT

Triple-negative breast cancer (TNBC) is associated with metabolic heterogeneity and poor prognosis with limited treatment options. New treatment paradigms for TNBC remains an unmet need. Thus, therapeutics that target metabolism are particularly attractive approaches. We previously designed organometallic Au(III) compounds capable of modulating mitochondrial respiration by ligand tuning with high anticancer potency in vitro and in vivo. Here, we show that an efficacious Au(III) dithiocarbamate (AuDTC) compound induce mitochondrial dysfunction and oxidative damage in cancer cells. Efficacy of AuDTC in TNBC mouse models harboring mitochondrial oxidative phosphorylation (OXPHOS) dependence and metabolic heterogeneity establishes its therapeutic potential following systemic delivery. This provides evidence that AuDTC is an effective modulator of mitochondrial respiration worthy of clinical development in the context of TNBC. ONE SENTENCE SUMMARY: Metabolic-targeting of triple-negative breast cancer by gold anticancer agent may provide efficacious therapy.


Subject(s)
Antineoplastic Agents , Triple Negative Breast Neoplasms , Humans , Animals , Mice , Oxidative Phosphorylation , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/metabolism , Gold/pharmacology , Gold/therapeutic use , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cell Line, Tumor
18.
Neurosurg Rev ; 46(1): 314, 2023 Nov 28.
Article in English | MEDLINE | ID: mdl-38012480

ABSTRACT

The purpose of this study was to systematically review studies in the literature to assess the superiority between microsurgery and radiosurgery regarding the efficacy in improving petroclival meningioma (PCM)-related trigeminal neuralgia (TN). PubMed, Embase, Web of Science, and Cochrane clinical trial databases were systematically searched from the inception until December 08, 2022. The overall proportion of patients with improved TN after treatment in all six included studies was 56% (95% confidence interval [CI], 35-76.9%). Higgins I2 statistics showed significant heterogeneity (I2 = 90%). Subgroup analysis showed that the proportion of improved TN was higher in the microsurgery group than that in the radiosurgery group (89%; 95% CI, 81-96.5% vs. 37%, 95% CI, 22-52.7%, respectively, p < 0.01). Subgroup analysis (for studies that documented the number of posttreatment Barrow Neurological Institute scores 1 and 2) revealed that the proportion of pain-free without medication after treatment was higher in the microsurgery group than that in the radiosurgery group (90.7%; 95% CI, 81-99.7% vs. 34.5%, 95% CI, 21.3-47.7.7%, respectively, p < 0.01). Based on the results of this meta-analysis, we concluded that microsurgery is superior to radiosurgery in controlling PCM-related TN.


Subject(s)
Meningeal Neoplasms , Meningioma , Radiosurgery , Skull Base Neoplasms , Trigeminal Neuralgia , Humans , Trigeminal Neuralgia/surgery , Meningioma/radiotherapy , Meningioma/surgery , Treatment Outcome , Radiosurgery/methods , Microsurgery , Skull Base Neoplasms/surgery , Meningeal Neoplasms/radiotherapy , Meningeal Neoplasms/surgery , Retrospective Studies
19.
Healthcare (Basel) ; 11(21)2023 Oct 27.
Article in English | MEDLINE | ID: mdl-37957984

ABSTRACT

Toxocara spp. is a zoonotic soil-transmitted parasite that infects canids and felids, which causes toxocariasis in humans, migrating to organ systems, including the lungs, the ocular system, and the central nervous system. Since Toxocara spp. is usually transmitted through soil, children tend to be more susceptible to infection. In order to monitor contamination with Toxocara spp. in children's play facilities in the Republic of Korea, we investigated 11,429 samples of soil from daycare centers, kindergartens, elementary schools, and parks across the country from January 2016 to December 2021. Since the Environmental Health Act in the Republic of Korea was enacted in March 2008, there have been sporadic reports of contamination by Toxocara spp. in children's activity zones. In this study, soil from children's play facilities in regions across the Republic of Korea was monitored according to the Korean standardized procedure to use it as basic data for preventive management and public health promotion. The national average positive rate was 0.16% (18/11,429), and Seoul showed a higher rate of 0.63% (2/318) than any other regions while Incheon, Daegu, Ulsan, Kangwon-do, Jeollabuk-do, and Jeollanam-do were negative (p < 0.05). The positive rates were as follows: 0.37% (4/1089) in daycare centers, 0.13% (3/2365) in kindergartens, 0.2% (7/4193) in elementary schools, 0.09% (1/1143) in apartments, and 0.14% (3/2198) in parks. In addition, it was confirmed that 0.2% (1/498) of elementary schools and 1.17% (2/171) of parks were re-contaminated among play facilities managed with the establishment of a regular inspection cycle. Consequently, there is an essential need for continuous monitoring of Toxocara spp. contamination and regular education for preschool and school children in order to prevent soil-borne parasite infections.

20.
Light Sci Appl ; 12(1): 265, 2023 Nov 07.
Article in English | MEDLINE | ID: mdl-37932249

ABSTRACT

Sepsis is a dysregulated immune response to infection that leads to organ dysfunction and is associated with a high incidence and mortality rate. The lack of reliable biomarkers for diagnosing and prognosis of sepsis is a major challenge in its management. We aimed to investigate the potential of three-dimensional label-free CD8 + T cell morphology as a biomarker for sepsis. This study included three-time points in the sepsis recovery cohort (N = 8) and healthy controls (N = 20). Morphological features and spatial distribution within cells were compared among the patients' statuses. We developed a deep learning model to predict the diagnosis and prognosis of sepsis using the internal cell morphology. Correlation between the morphological features and clinical indices were analysed. Cell morphological features and spatial distribution differed significantly between patients with sepsis and healthy controls and between the survival and non-survival groups. The model for predicting the diagnosis and prognosis of sepsis showed an area under the receiver operating characteristic curve of nearly 100% with only a few cells, and a strong correlation between the morphological features and clinical indices was observed. Our study highlights the potential of three-dimensional label-free CD8 + T cell morphology as a promising biomarker for sepsis. This approach is rapid, requires a minimum amount of blood samples, and has the potential to provide valuable information for the early diagnosis and prognosis of sepsis.

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