Petahertz-scale spectral broadening and few-cycle compression of Yb:KGW laser pulses in a pressurized, gas-filled hollow-core fiber.

We demonstrate efficient generation of coherent super-octave pulses via a single-stage spectral broadening of a Yb:KGW laser in a single, pressurized, Ne-filled, hollow-core fiber capillary. Emerging pulses spectrally spanning over more than 1 PHz (250-1600 nm) at a dynamic range of ∼60 dB, and an excellent beam quality open the door to combining Yb:KGW lasers with modern light-field synthesis techniques. Compression of a fraction of the generated supercontinuum to intense (8 fs, ∼2.4 cycle, ∼650 µJ) pulses allows convenient use of these novel laser sources in strong-field physics and attosecond science.

Short-term neonatal and long-term infant outcome of late-preterm twins: nationwide population-based study.

OBJECTIVES: To evaluate the short- and long-term outcome of late-preterm compared with term birth in twin pregnancy. METHODS: This retrospective observational cohort study included all women who had a twin delivery between 1 January 2007 and 31 December 2010 recorded in the claims database of the Korea National Health Insurance, with at least one follow-up recorded in the database of the National Health Screening Program for Infants and Children. Outcomes were analyzed at the pregnancy level, with adverse outcome being defined as an adverse outcome in one or both twins, identified by a diagnosis according to the International Classification of Diseases 10th Revision. The primary short-term outcome was composite morbidity, which included any of the following: transient tachypnea, respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage and bronchopulmonary dysplasia. Long-term adverse outcome included any neurological or neurodevelopmental outcome, defined by prespecified neurological and developmental diagnoses; these were assessed by following up all neonates until the end of 2018, by which time they were 8-11 years of age. Outcomes were compared between twins delivered late preterm (34 + 0 to 36 + 6 weeks) and those delivered at term (≥ 37 weeks). RESULTS: Among 17 189 women who delivered twins at ≥ 34 weeks of gestation during the study period, 5032 (29.27%) women delivered in the late-preterm period. On multivariate analysis, compared with the twins delivered at term, the late-preterm twins had an increased risk for the primary short-term outcome of composite morbidity (adjusted odds ratio (aOR), 2.09; 95% CI, 1.90-2.30), including transient tachypnea (aOR, 1.85; 95% CI, 1.64-2.09), respiratory distress syndrome (aOR, 2.31; 95% CI, 2.04-2.62), necrotizing enterocolitis (aOR, 2.10; 95% CI, 1.20-3.69) and intraventricular hemorrhage (aOR, 2.13; 95% CI, 1.46-3.11). For the long-term outcome, the late-preterm twins also had an increased risk for any neurological or neurodevelopmental outcome (adjusted hazard ratio, 1.14; 95% CI, 1.07-1.21). CONCLUSIONS: Twins delivered in the late-preterm period have an increased risk for short- and long-term morbidity compared with twins delivered at term. These results should be considered when determining the timing of delivery in uncomplicated twin pregnancy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Incidence of subsequent osteoporotic fractures after distal radius fractures and mortality of the subsequent distal radius fractures: a retrospective analysis of claims data of the Korea National Health Insurance Service.

A better understanding of the features of subsequent fractures after distal radius fracture (DRF) is important for the prevention of further osteoporotic fractures. This study found that the cumulative incidence of subsequent osteoporotic fractures in South Korea increased over time and that the mortality rates of subsequent DRFs were lower than those of first-time DRFs. INTRODUCTION: We examined the incidence of osteoporotic fractures following distal radius fractures (DRFs) and the mortality rate after subsequent DRFs using claims data from the Korea National Health Insurance (KNHI) Service. METHODS: We identified records for 41,417 patients with first-time DRFs in 2012. The occurrence of osteoporotic fractures of the spine, hip, wrist, and humerus at least 6 months after the index DRF was tracked through 2016. All fractures were identified by specific diagnosis and procedure codes. One-year mortality rates and standardized mortality ratios (SMRs) for initial and subsequent DRFs were calculated for all patients. RESULTS: The 4-year cumulative incidence of all subsequent osteoporotic fractures was 14.74% (6105/41,417; 9.47% in men, 15.9% in women). The number of associated subsequent fractures was 2850 for the spine (46.68%), 2271 for the wrist (37.2%), 708 for the hip (11.6%), and 276 for the humerus (4.52%). The cumulative mortality rate 1 year after the first-time and subsequent DRF was 1.47% and 0.71%, respectively, and the overall SMR was 1.48 (95% CI: 1.37-1.61) and 0.71 (95% CI: 0.42-1.21), respectively. CONCLUSION: The cumulative incidence of osteoporotic fractures following DRFs increased over the study period and was higher among women. The cumulative mortality rates and SMRs of subsequent DRFs were lower than those of first-time DRFs at the 1-year follow-up. Given the increasing incidence rate of DRFs, the incidence of subsequent osteoporotic fractures may also increase.

Thyroid surgery during coronavirus-19 pandemic phases I, II and III: lessons learned in China, South Korea, Iran and Italy.

OBJECTIVE: We compared demographic and clinic-pathological variables related to the number of surgeries for thyroid conditions or for cancer, morbidity, and fine needle aspiration (FNA) practices among Covid19 pandemic phases I, II, III and the same seasonal periods in 2019. METHODS: The prospective database of the Division of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Changchun, China was used for this study. Covid19 emergency levels were stratified according to the World Health Organization: phase I (January 25-February 25, 2020), phase II (February 26-March 19), phase III (March 20-April 20). RESULTS: There were fewer outpatient FNAs and surgeries in 2020 than in 2019. There were no thyroid surgeries during phase I. There were also fewer surgeries for cancer with a significant reduction of advanced stage cancer treatments, mainly stage T1b N1a in phase II and T3bN1b in phase III. Operative times and postoperative stays were significantly shorter during the pandemic compared to our institutional baseline. In phase III, vocal cord paralysis (VCP) increased to 4.3% of our baseline numbers (P = 0.001). There were no cases of Covid19-related complications during the perioperative period. No patients required re-admission to the hospital. CONCLUSION: The Covid19 outbreak reduced thyroid surgery patient volumes. The decrease of Covid19 emergency plans contributed to unexpected outcomes (reduction of early stage cancer treatment, decreased operative times and hospital stays, increased VCP rate).

Extended approach or usage of nasoseptal flap is a risk factor for olfactory dysfunction after endoscopic anterior skullbase surgery: results from 928 patients in a single tertiary center.

BACKGROUND: The aim of this study was to compare olfactory function change in patients who underwent endoscopic skull-base surgery. METHODOLOGY: A total of 928 patients were included in this retrospective study. Olfactory function was measured using the non- validated Likert scale (0â€"100), the Cross-Cultural Smell Identification Test (CC-SIT) and the butanol threshold test (BTT). Patients were divided into two groups: an endoscopic trans-sellar approach group (ETA, n = 768) and an extended endoscopic endonasal approach group (EEEA, n = 160). The ETA group was sub-divided into Nasoseptal flap (NSF) and no NSF groups. RESULTS: Non-validated olfactory function significantly worsened in the EEEA and ETA-NSF groups compared with that in the ETA- no NSF group for at least 6 months post-operatively. Validated olfactory impairment (BTT and CC-SIT) was also significantly worse in the EEEA and NSF groups compared with that in the ETA-no NSF group 3 months post-operatively. Additionally, the degrees of non-validated and validated olfactory deterioration were not significantly different between the EEEA and ETA-NSF groups. We also found that CC-SIT score changes were significantly impaired in tuberculum sellae meningioma patients than in craniopharyn- gioma patients. CONCLUSIONS: We conclude that NSF was the key factor that led to olfactory impairment after endoscopic skull-base surgery.

Symptom and digital chest X-ray TB screening in South African prisons: yield and cost-effectiveness.

BACKGROUND: Correctional inmates are at a high risk of tuberculosis (TB). The optimal approach to screening this population is unclear.METHODS: We retrospectively reviewed records from TB screening in 64 correctional facilities in South Africa between January 2015 and July 2016. Inmates received symptom screening (any of cough, fever, weight loss, or night sweats) combined with digital chest X-ray (CXR), when available. CXRs were assessed as 'abnormal' or with no abnormalities. Inmates with either a symptom or an 'abnormal' CXR were asked to provide a single spot sputum for Xpert® MTB/RIF testing. We estimated the incremental cost-effectiveness ratio (ICER) per additional TB case detected using CXR screening among asymptomatic inmates.RESULTS: Of 61 580 inmates, CXR screening was available for 41 852. Of these, 19 711 (47.1%) had TB symptoms. Among 22 141 inmates without symptoms, 1939/19 783 (9.8%) had an abnormal CXR, and 8 (1.2%) were Xpert-positive among those with Xpert tests done. Of 14 942 who received symptom screening only and had symptoms, 84% (12 616) had an Xpert result, and 105 (0.8%) were positive. The ICER for CXR screening was US$22 278.CONCLUSION: Having CXR in addition to symptom screening increased yield but added considerable cost. A major limitation of screening was the low specificity of the symptom screen.

STIM1 knock-down decreases the affinity of obinutuzumab for CD20 by altering CD20 localization to Triton-soluble membrane.

Obinutuzumab is thought to exert its effects through its high antibody-dependent cellular cytotoxicity (ADCC) via glyco-engineering of the Fc region. In addition, obinutuzumab causes direct binding-induced cell death (DCD) only by specifically binding to its target CD20, a Ca2+ channel. However, the specific features of CD20 related to obinutuzumab binding-induction of cell death are not clearly understood. In this study, we evaluated the relationship between the Ca2+ channel features of CD20 as a store-operated Ca2+ channel (SOC) and obinutuzumab binding-induced cell death. Ca2+ channel function and biochemical analysis revealed that CD20 is an Orai1- and stromal interaction molecule (STIM1)-dependent Ca2+ pore. However, binding of obinutuzumab on CD20 did not have any effect on Ca2+ influx activity of CD20; the direct cell death rate mediated by obinutuzumab binding was almost equivalent with or without the extracellular Ca2+ condition. Given the apparent interaction between STIM1 and CD20, we observed Triton-X solubilized obinutuzumab-bound CD20 accompanied by STIM1. Subsequently, obinutuzumab binding and cell death were decreased by STIM1 knock-down in Ramos B cells. Thus, STIM1 directly contributes to cell death by increasing the affinity of cells for obinutuzumab by transferring CD20 to the Triton-soluble membrane region.

Relationship between smoking and spontaneously healed pulmonary TB on chest radiography in a South Korean population.

SETTING: The Korea National Health and Nutrition Examination Survey is a national, population-based, cross-sectional surveillance programme.OBJECTIVE: 1) To investigate the prevalence of spontaneously healed pulmonary tuberculosis (SHPTB) on chest radiographs (CXRs) in South Korea, as well as its demographic and clinical associations, and 2) to determine the relationship between SHPTB and smoking.DESIGN: People with normal findings on CXRs (n = 24 190) and those with SHPTB (n = 1863) were compared in univariate, bivariate and multivariate analyses with respect to smoking and demographic and clinical factors.RESULTS: The prevalence of SHPTB was 7.2%. The proportion of patients with SHPTB tended to be higher in males, people of older age, ever smokers, as well as people with low body mass index and low education level. In bivariate analysis, after adjustments for age and sex, SHPTB was found more often among ex-smokers (P = 0.005) and current smokers (P = 0.024) than in non-smokers. Multivariate analyses revealed increased relative odds for SHPTB with increased age (P < 0.001), male sex (P < 0.001) and ex-smoker status (P = 0.016). Passive smoking was also significantly associated with SHPTB (P = 0.022).CONCLUSION: In addition to increasing the risk of active TB and negatively affecting the outcome of TB treatment, smoking is also associated with SHPTB, as detected on CXRs.

Inhibitory effects of herbal decoction Ojeoksan on proliferation and migration in vascular smooth muscle cells.

The proliferation of vascular smooth muscle cells plays a crucial role in pathogenesis of cardiovascular disease. The principal objective of this study was to determine the effects of Ojeoksan (OJS) on human aortic smooth muscle cell (HASMC) proliferation induced by tumor necrosis factor α (TNF-aα). Thymidine incorporation after TNF-α treatment was increased and this effect was inhibited significantly by OJS treatment. HASMC proliferation and migration by kinetic live cell imaging were also reduced by treatment with OJS. TNF-α induced the expression of cyclins/cyclin-dependent kinases (CDKs) and reduced the expression of p21waf1/cip1/p27kip1. However, OJS also attenuated the expression of TNF-α-induced cell-cycle regulatory proteins. The results of Western blot analysis demonstrated that the TNF-α treated HASMC secreted gelatinases, probably including MMP-2/-9, which may be involved in the invasion and migration of HASMC. Additionally, OJS suppressed the mRNA expression levels of matrix metalloproteinase-2/-9 (MMP-2/-9) in a dose-dependent manner. OJS inhibited the production of TNF-α-induced hydrogen peroxide (H2O2) and the formation of DCF-sensitive intracellular reactive oxygen species (ROS). Further, OJS suppressed the nuclear translocation and phosphorylation of inhibitor of kappa B-α (IκB-α) of nuclear factor κB (NF-κB) under TNF-α conditions. Our results demonstrate that OJS exerts inhibitory effects on TNF-α-induced HASMC proliferation and migration, suggesting the involvement of the inhibition of both MMP-2 and MMP-9 expressions, and the downregulation of ROS/NF-κB signaling. Thus, herbal decoction OJS may be a possible therapeutic approach to the inhibition of cardiovascular disease including atherosclerosis.

Home-based intervention to test and start (HITS) protocol: a cluster-randomized controlled trial to reduce HIV-related mortality in men and HIV incidence in women through increased coverage of HIV treatment.

BACKGROUND: To realize the full benefits of treatment as prevention in many hyperendemic African contexts, there is an urgent need to increase uptake of HIV testing and HIV treatment among men to reduce the rate of HIV transmission to (particularly young) women. This trial aims to evaluate the effect of two interventions - micro-incentives and a tablet-based male-targeted HIV decision support application - on increasing home-based HIV testing and linkage to HIV care among men with the ultimate aim of reducing HIV-related mortality in men and HIV incidence in young women. METHODS/DESIGN: This is a cluster randomized trial of 45 communities (clusters) in a rural area in the uMkhanyakude district of KwaZulu Natal, South Africa (2018-2021). The study is built upon the Africa Health Research Institute (AHRI)'s HIV testing platform, which offers annual home-based rapid HIV testing to individuals aged 15 years and above. In a 2 × 2 factorial design, individuals aged ≥15 years living in the 45 clusters are randomly assigned to one of four arms: i) a financial micro-incentive (food voucher) (n = 8); ii) male-targeted HIV specific decision support (EPIC-HIV) (n = 8); iii) both the micro incentives and male-targeted decision support (n = 8); and iv) standard of care (n = 21). The EPIC-HIV application is developed and delivered via a tablet to encourage HIV testing and linkage to care among men. A mixed method approach is adopted to supplement the randomized control trial and meet the study aims. DISCUSSION: The findings of this trial will provide evidence on the feasibility and causal impact of two interventions - micro-incentives and a male-targeted HIV specific decision support - on uptake of home-based HIV testing, linkage to care, as well as population health outcomes including population viral load, HIV related mortality in men, and HIV incidence in young women (15-30 years of age). TRIAL REGISTRATION: This trial was registered on 28 November 2018 on, identifier https://clinicaltrials.gov/ .

Classifying pain in transoral endoscopic thyroidectomy.

PURPOSES: Knowledge of visual analog scale (VAS) pain assessment for transoral endoscopic thyroidectomy vestibular approach (TOETVA) is limited. The purpose of this analysis was to classify the postoperative discomfort scores in patients undergoing TOETVA compared to open thyroidectomy. METHODS: Observational clinical study of patients who underwent thyroidectomy by VAS pain assessment from September 2016 to March 2017. Patients were stratified into two groups: patients eligible for TOETVA (Group TOETVA) and non-candidates for endoscopic intervention (open thyroidectomy approach-OTA). VAS was recorded in the recovery room, at 24 h, + 2, + 5, + 15, + 30, + 90 days, and 6 months after surgery. Pain assessment was stratified in VAS-lower lip, VAS-chin, VAS-jaw, VAS-anterior neck, VAS-cervical/back, VAS-swallowing, VAS-brushing, VAS-speaking, and VAS-shaving. Secondary outcome assessed were analgesic rescue dose, morbidity, operative notes, hospital stay, and histopathology. RESULTS: 41 TOETVA and 45 OTA constituted the analysis. There were differences between the TOETVA and OTA for age, gland volume, mean nodule diameter, coexistence thyroiditis, bilateral procedures, and use of drain. Operative time was longer in TOETVA. Results indicated that TOETVA was associated with reduced neck, cervical back, and swallowing VAS scores in the 24 h after surgery. Conversely, jaw and brushing teeth resulted in higher VAS score in TOETVA group. OTA patients never experienced lower lip or chin pain. The use of rescue analgesics did not differ between the two groups. CONCLUSIONS: VAS was used to measure treatment outcome in TOETVA. VAS scores achieved overall a minimal clinical importance difference from the two procedures. There appears to be both a short- and long-term different range of interpretations of pain between TOETVA and OTA.

Inflammatory cytokines and mononuclear cells in sudden sensorineural hearing loss.

OBJECTIVE: This study evaluated tumour necrosis factor-α, interleukins 10 and 12, and interferon-γ levels, peripheral blood mononuclear cells, and clusters of differentiation 17c and 86 expression in unilateral sudden sensorineural hearing loss. METHODS: Twenty-four patients with unilateral sudden sensorineural hearing loss, and 24 individuals with normal hearing and no history of sudden sensorineural hearing loss (who were attending the clinic for other problems), were enrolled. Peripheral blood mononuclear cells, and clusters of differentiation 11c and 86 were isolated and analysed. Plasma and supernatant levels of tumour necrosis factor-α, interferon-γ, and interleukins 10 and 12 were measured. RESULTS: There were no significant differences with respect to age and gender. Monocyte population, mean tumour necrosis factor-α level and cluster of differentiation 86 expression were significantly increased in the study group compared to the control group. However, interferon-γ and interleukin 12 levels were significantly decreased. The difference in mean interleukin 10 level was not significant. CONCLUSION: Increases in tumour necrosis factor-α level and monocyte population might play critical roles in sudden sensorineural hearing loss. This warrants detailed investigation and further studies on the role of dendritic cells in sudden sensorineural hearing loss.

Impact of antimicrobial treatment duration on outcome of Staphylococcus aureus bacteraemia: a cohort study.

OBJECTIVES: To assess the outcome of Staphylococcus aureus bacteraemia (SAB) according to factors associated with necessity for longer treatment in conjunction with the duration of treatment. METHODS: We prospectively collected the data of patients with SAB consecutively during 12 to 39 months from 11 hospitals. If multiple episodes of SAB occurred in one patient, only the first episode was enrolled. Factors associated with necessity for longer treatment were defined as follows: persistent bacteraemia, metastatic infection, prosthesis and endocarditis. If any of the factors were present, then the case was defined as longer antibiotic treatment warranted (LW) group; those without any factors were defined as shorter antibiotic treatment sufficient (SS) group. Poor outcome was defined as a composite of 90-day mortality or 30-day recurrence. Duration of antibiotic administration was classified as <14 or ≥14 days in the SS group and <28 or ≥28 days in the LW group. RESULTS: Among 2098 cases, the outcome was analysed in 1866 cases, of which 591 showed poor outcome. The SS group accounted for 964 cases and the LW group for 852. On multivariate analysis, age over 65 years, pneumonia, higher Sequential Organ Failure Assessment (SOFA) score and chronic liver diseases were risk factors for poor outcome. Administration of antibiotics less than the recommendation was associated with poor outcome, but this significance was observed only in the LW group (adjusted odds ratio = 1.68; 95% confidence interval, 1.00-2.83; p 0.05). CONCLUSIONS: Inappropriately short antibiotic treatment was associated with poor outcome in the LW group. Vigilant evaluation for risk factors to determine the duration of treatment may improve the outcome among patients with SAB.

Coil Embolization in Patients with Recurrent Cerebral Aneurysms Who Previously Underwent Surgical Clipping.

BACKGROUND AND PURPOSE: Surgical revision of recurrent cerebral aneurysms is technically difficult. Therefore, coil embolization has been used as an alternative in these cases. The aim of this study was to evaluate the clinical and angiographic outcomes of coil embolization in patients with recurrent cerebral aneurysms after microsurgical clipping. MATERIALS AND METHODS: Between May 1999 and February 2016, nineteen patients with 19 recurrent aneurysms who previously underwent surgical clipping were treated by coil embolization. RESULTS: Nine patients presented with subarachnoid hemorrhage (47.4%). The interval between surgical clipping and coil embolization was 143.5 ± 66.1 months (range, 43-276 months). Single- or double-catheter coil embolization was performed in 16 patients. A balloon (n = 1) and stents (n = 2) were used to assist the coil embolization in 3 patients. Immediate radiologic findings after coil embolization showed complete occlusion in 10 patients, a residual neck in 8 patients, and a residual sac in 1 patient. Procedure-related permanent morbidity occurred in 1 patient. The mean clinical follow-up was 58.3 ± 38.8 months. Poor clinical outcomes (modified Rankin Scale score = ≥3) at the end of the clinical follow-up were reported in 5 patients (26.3%). Angiographic follow-up was available for 12 patients (63.2%). Major recurrence was detected in 5 patients (41.7%), and a tendency for aneurysm regrowth rather than coil compaction was noted in all cases. CONCLUSIONS: In our series, coil embolization for recurrent aneurysms after surgical clipping was feasible but had a high recurrence rate and tended to result in aneurysm regrowth rather than coil compaction.

Weaning of Veno-venous Bypass in Liver Transplantation: A Single Center Experience.

BACKGROUND: Veno-venous bypass (VVB) has been used in liver transplantation (LT) to minimize hemodynamic instability during caval anastomosis of anhepatic phase. With the introduction of the piggyback (PB) technique, which is a caval-sparing technique, the use of VVB progressively decreased over the world. The aim of this study was to introduce our experience using VVB with the focus on its weaning process. METHODS: A total of 300 consecutive LT cases from May 1996 to November 2003 were examined. Except for pediatric LT, 242 LT cases were investigated to evaluate the trends in VVB use, surgical technique, the amount of transfusion requirements, and durations of operation and anhepatic phase. RESULTS: For the early 100 LT cases, VVB was used in 97.5% of recipients, especially in all the recipients of deceased donor LT (DDLT). Then, the frequency of VVB use was decreased, and VVB was not used after the 268th recipient. In DDLT, the PB technique was first introduced in the 58th recipient and became a routine procedure of the DDLT since the 191th recipient. Living donor LT was increased, and the amount of transfusion requirement, duration of operation, and duration of anhepatic phase was reduced over time. CONCLUSIONS: The increasing experience and sophisticated surgical and anesthetic techniques were important factors responsible for the weaning of VVB. The advancement of the PB technique used in living donor LT might be a main factor of its weaning.

Efficacy of Ultralow-Dose Valganciclovir Chemoprophylaxis for Cytomegalovirus Infection in ABO-Incompatible Kidney Transplantation Recipients.

BACKGROUND: Cytomegalovirus (CMV) infection can increase morbidity and mortality in kidney transplant (KT) patients. Chemoprophylaxis with valganciclovir (VGCV) is recommended for ABO-incompatible (ABOi) KT patients as it significantly reduces CMV disease and infection. The recommended dose of VGCV for prevention of CMV in a KT recipient is 900 mg once daily, and the treatment duration is 6 months. However, because it is expensive, sufficient amounts might not be administered. METHODS: We investigated whether ultralow-dose VGCV (450 mg every other day) and short dosing period (3 months) was sufficient to prevent CMV infection after ABOi KT. We retrospectively evaluated 74 adult CMV-seropositive donor/CMV-seropositive recipient (D+/R+) ABOi KT recipients from June 2009 to July 2016 who received ultralow-dose VGCV prophylaxis for 3 months. The primary outcome was occurrence of CMV infection. Secondary outcomes were leukopenia and thrombocytopenia. RESULT: All patients received intravenous rituximab 200 mg once and plasmapheresis for reduction of anti-A/B antibodies and interleukin-2 antibodies before undergoing ABOi KT. Mean prophylaxis and follow-up durations were 3 and 52 months, respectively. One patient died of bacterial pneumonia. Four patients lost graft function and were undergoing hemodialysis; 3 cases were caused by antibody-mediated rejection, and 1 was due to mechanical complication after surgery. Fortunately, CMV infection did not occur in any patient. CONCLUSION: Ultralow-dose VGCV is an effective prophylaxis for D+/R+ ABOi KT recipients. Especially, ultralow-dose VGCV CMV infection prevention protocol in Asian populations reduced the side effects and cost.

Src-type tyrosine kinase p56lck is critical for thymic stromal lymphopoietin-induced allergic rhinitis.

BACKGROUND: Thymic stromal lymphopoietin (TSLP) is a regulator of mast cell-mediated allergic inflammatory reactions, but the manner in which TSLP contributes to allergic rhinitis (AR) remains unclear. OBJECTIVE: Here, we sought to determine that TSLP plays a crucial role in AR by interacting with Src-type tyrosine kinase p56lck and STAT6 and promoting mast cells degranulation. METHODS: The effects of TSLP on mast cell degranulation and AR were analysed in human mast cell line (HMC-1 cells), ovalbumin (OVA)-induced AR animal model, and human subjects. Small interfering RNA experiments were performed in HMC-1 cells and OVA-induced AR model. Immune responses were analysed by enzyme-linked immunosorbent assay, Western blotting, immunoprecipitation, and histological studies. RESULTS: Thymic stromal lymphopoietin levels and mast cell-derived p56lck activation were elevated in human subjects with AR, and in AR mice, exogenous TSLP accelerated TH2-allergic inflammatory reactions by up-regulating p56lck and STAT6. On the other hand, depletion of TSLP, p56lck, and STAT6 ameliorated clinical symptoms in AR mice. The selective inhibitor of p56lck, damnacanthal, inhibits AR reactions. CONCLUSION: Collectively, these observations suggest a role for TSLP/p56lck/STAT6 in AR and offer insight into potential therapeutic strategies.

Cost-effectiveness of contact screening strategies for tuberculosis among high-school adolescents in South Korea.

BACKGROUND: Effective latent tuberculous infection (LTBI) control among adolescents is a critical component of tuberculosis (TB) elimination in Korea. OBJECTIVE: To compare the cost-effectiveness of the following contact screening strategies for LTBI among high-school adolescents after TB outbreaks: QuantiFERON®-TB Gold In-Tube (QFT-GIT), the tuberculin skin test (TST), or TST/QFT-GIT (two-step strategy). METHOD: The costs of post-TB outbreak screening strategies were calculated using a mixed (top-down and bottom-up) cost analysis method and expressed in 2015 US dollars. Cost-effectiveness was evaluated using a decision analysis model from the health system perspective, comparing cumulative health care costs and the total number of TB cases averted. RESULTS: In a hypothetical cohort of 1000 students, screening using the TST-alone strategy averted 1.6 TB cases at a total cost of US$52 566. The QFT-GIT-alone strategy helped avert 2.0 TB cases, but was associated with a much higher total cost (US$108 435), resulting in an incremental cost-effectiveness ratio of US$140 933/TB case averted. The two-step TST/QFT-GIT strategy was worse than the TST-alone strategy, averting 1.3 TB cases at US$75 267. CONCLUSION: The TST-alone strategy was the most cost-effective; the QFT-GIT-alone strategy averted the greatest number of TB cases but incurred the highest cost in contact investigation for school TB outbreaks.