Search for Antideuterons of Cosmic Origin Using the BESS-Polar II Magnetic-Rigidity Spectrometer.

We searched for antideuterons (d[over ¯]'s) in the 4.7×10^{9} cosmic-ray events observed during the BESS-Polar II flight at solar minimum in 2007-2008 but found no candidates. The resulting 95% C.L. upper limit on the d[over ¯] flux is 6.7×10^{-5} (m^{2} s sr GeV/n)^{-1} in an energy range from 0.163 to 1.100 GeV/n. The result has improved by more than a factor of 14 from the upper limit of BESS97, which had a potential comparable to that of BESS-Polar II in the search for cosmic-origin d[over ¯]'s and was conducted during the former solar minimum. The upper limit of d[over ¯] flux from BESS-Polar II is the first result achieving the sensitivity to constrain the latest theoretical predictions.

Outcome and etiology of fetal pleural effusion, fetal ascites and hydrops fetalis after fetal intervention: retrospective observational cohort from a single institution.

OBJECTIVES: Non-immune hydrops fetalis (NIHF) is the pathological accumulation of fluids in fetal compartments, without maternal isoimmunization. Fetal interventions (e.g. shunting, fetal paracentesis, fetal thoracocentesis, fetal pleurodesis) are used to alleviate fluid accumulations, but the outcome is uncertain because the underlying causes of NIHF vary. We aimed to explore the etiology and long-term outcome of NIHF after fetal intervention. METHODS: This was a retrospective review of fetuses with NIHF, defined by the presence of fetal ascites, pleural or pericardial effusion, skin edema or cystic hygroma, or a combination of these features, who underwent intervention at our institution during the period 2012-2021. Clinical surveillance, genetic analysis and viral infection screening were used to define the etiology. Chart reviews and telephone interviews were conducted to assess the long-term outcomes. RESULTS: In total, 55 fetuses were enrolled and 46 cases had final follow-up data after delivery. Etiology was identified in 33 cases, including four for which the underlying causes were not identified initially using small-gene-panel tests but which were later diagnosed with monogenic disorders by whole-exome sequencing (WES). Twenty-three cases with follow-up survived, having a follow-up period of 2-11 years at the time of writing, of which 17 were healthy. All 11 cases initially presenting as congenital chylothorax survived with favorable outcome. CONCLUSIONS: The etiologies of NIHF are heterogeneous, and the long-term (spanning 2-11 years) outcome of fetal intervention varies, according to the underlying etiology, with cases caused by congenital chylothorax having the best prognosis. Genome-wide tests, such as WES, may be helpful in determining the underlying condition in cases caused by a genetic disorder, and this may affect fetal therapy approaches in the future. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

A candidate super-Earth planet orbiting near the snow line of Barnard's star.

Barnard's star is a red dwarf, and has the largest proper motion (apparent motion across the sky) of all known stars. At a distance of 1.8 parsecs1, it is the closest single star to the Sun; only the three stars in the α Centauri system are closer. Barnard's star is also among the least magnetically active red dwarfs known2,3 and has an estimated age older than the Solar System. Its properties make it a prime target for planetary searches; various techniques with different sensitivity limits have been used previously, including radial-velocity imaging4-6, astrometry7,8 and direct imaging9, but all ultimately led to negative or null results. Here we combine numerous measurements from high-precision radial-velocity instruments, revealing the presence of a low-amplitude periodic signal with a period of 233 days. Independent photometric and spectroscopic monitoring, as well as an analysis of instrumental systematic effects, suggest that this signal is best explained as arising from a planetary companion. The candidate planet around Barnard's star is a cold super-Earth, with a minimum mass of 3.2 times that of Earth, orbiting near its snow line (the minimum distance from the star at which volatile compounds could condense). The combination of all radial-velocity datasets spanning 20 years of measurements additionally reveals a long-term modulation that could arise from a stellar magnetic-activity cycle or from a more distant planetary object. Because of its proximity to the Sun, the candidate planet has a maximum angular separation of 220 milliarcseconds from Barnard's star, making it an excellent target for direct imaging and astrometric observations in the future.

Search for Boosted Dark Matter in COSINE-100.

We search for energetic electron recoil signals induced by boosted dark matter (BDM) from the galactic center using the COSINE-100 array of NaI(Tl) crystal detectors at the Yangyang Underground Laboratory. The signal would be an excess of events with energies above 4 MeV over the well-understood background. Because no excess of events are observed in a 97.7 kg·yr exposure, we set limits on BDM interactions under a variety of hypotheses. Notably, we explored the dark photon parameter space, leading to competitive limits compared to direct dark photon search experiments, particularly for dark photon masses below 4 MeV and considering the invisible decay mode. Furthermore, by comparing our results with a previous BDM search conducted by the Super-Kamionkande experiment, we found that the COSINE-100 detector has advantages in searching for low-mass dark matter. This analysis demonstrates the potential of the COSINE-100 detector to search for MeV electron recoil signals produced by the dark sector particle interactions.

Isolation of Streptomycin-Resistant Erwinia pyrifoliae in Korea.

As a black shoot blight disease-causing agent, Erwinia pyrifoliae was first reported in 1995 in Korea. A total of 101 isolates of E. pyrifoliae were isolated from samples showing bacterial symptoms collected from apple and pear orchards between 2020 and 2021. These isolates were screened for streptomycin resistance, with one from an orchard in Gwangju showing resistance at 100 µg/ml streptomycin. This streptomycin-resistant E. pyrifoliae (EpSmR) isolate was identified via polymerase chain reaction amplification of the strA/strB gene and an internal region of the ribosomal rpsL gene containing codon 43. EpSmR has a point mutation that altered this codon from lysine (AAA) to threonine (ACA). The strA and strB genes were not identified in EpSmR. EpSmR showed a high resistance to streptomycin (>50,000 µg/ml). This is the first study reporting EpSmR, which emerged due to a mutation in codon 43 of the rpsL gene.

First Report of Pseudomonas cichorii Causing Bacterial vein necrosis on Perilla plants [Perilla frutescens (L.) Britton.] in South Korea.

Perilla (Perilla frutescens L.) is the second most important upland crop and the third largest edible oil crop in Korea (Shin and Kim 1994). During a disease survey in Busan, Korea in September 2021, symptoms of vein necrosis were observed in perilla plants, with incidences of approximately 30% and 50% in two fields. Symptoms of spots on the perilla appeared as leaf dryness and spots with water-soaked blotches largely concentrated on the mid-veins of leaves. The lesions were initiated with water-soaked spots on the leaf or stem and gradually turned black or brown. Necrosis was also observed in the stems. A bacterium was isolated on Luria-Bertani (LB) agar from diseased leaf tissues that were surface-disinfected with 70% ethyl alcohol for 3-5 min and then washed with sterile water three times. Three pieces of sterilized leaf tissue (size: 0.5 × 0.5 cm) were mixed with 500 µL sterile water for 30 min, and then the suspension was serially diluted and spread on LB agar. Subsequently, isolates were cultivated on LB agar and King's Medium B agar (KMB) (Schaad et al. 2001), and they were predominantly cream-colored and circular bacterial colonies with undulated margins. The bacterial colonies on KMB displayed fluorescence under 365 nm UV light. The isolates were analyzed with the GEN III MicroPlate (Biolog, Hayward, CA, USA), and all isolates were identified as Pseudomonas cichorii, a devastating plant bacterium that damages a wide range of host plants worldwide, including in South Korea (Hikichi et al. 2013; Ramkumar et al. 2015). To identify the species of the bacterial pathogen, genomic DNA of four isolates (BS4922, BS4167, BS4345, and BS4560) was extracted, and the 16S rRNA gene and hrcRST gene were amplified with universal primers, 27F/1492R and Hcr1/Hcr2, and sequencing was then done (Patel et al. 2019). In the BLAST analysis, the 16S rRNA sequences (GenBank OM060656, OM275434, OM275435, OM275436) showed a 100% and 99% similarity to P. cichorii strains MAFF 302698 (AB724286) and P. cichorii strain Pc-Gd-4 (KU923373), respectively. Further, hrcRST gene sequences (GenBank OM143596, OM268864, OM268865, and OM268866) showed high similarity (>99%) with P. cichorii strain P16-51 (MG518230). A pathogenicity test of the four isolates was performed on 3 - 4 weeks old perilla plants by creating wounds with a needle on the lower leaves and stems, and then the plants were inoculated by spraying inoculum (108 CFU/ml). The plants that served as the negative control were wounded and sprayed with unsterilized water. The inoculated perilla plants were placed in a greenhouse at 28 ± 2oC , 80-85% relative humidity, and a natural photoperiod. The inoculation site began to show symptoms of water-soaked brown lesions. Disease symptoms such as leaf dryness, water-soaked blotches on the mid-vein of leaves, and necrosis on plant stems were observed in the inoculated plants 7-10 days after inoculation, whereas the plants of the negative control group did not show any symptoms. The bacteria were re-isolated from the diseased tissues of the plants, and DNA sequence analysis identified them as P. cichorii. Additionally, all isolates induced hypersensitivity reactions in tobacco and tomato leaves within 24 h after inoculation. To our knowledge, this is the first report of P. cichorii infecting perilla in South Korea. The findings in this study will provide the basic information for the development of diagnostic tools and management measures against P. cichorii in perilla.

Optical design and performance of the biological small-angle X-ray scattering beamline at the Taiwan Photon Source.

The optical design and performance of the recently opened 13A biological small-angle X-ray scattering (SAXS) beamline at the 3.0 GeV Taiwan Photon Source of the National Synchrotron Radiation Research Center are reported. The beamline is designed for studies of biological structures and kinetics in a wide range of length and time scales, from angstrom to micrometre and from microsecond to minutes. A 4 m IU24 undulator of the beamline provides high-flux X-rays in the energy range 4.0-23.0 keV. MoB4C double-multilayer and Si(111) double-crystal monochromators (DMM/DCM) are combined on the same rotating platform for a smooth rotation transition from a high-flux beam of ∼4 × 1014 photons s-1 to a high-energy-resolution beam of ΔE/E ≃ 1.5 × 10-4; both modes share a constant beam exit. With a set of Kirkpatrick-Baez (KB) mirrors, the X-ray beam is focused to the farthest SAXS detector position, 52 m from the source. A downstream four-bounce crystal collimator, comprising two sets of Si(311) double crystals arranged in a dispersive configuration, optionally collimate the DCM (vertically diffracted) beam in the horizontal direction for ultra-SAXS with a minimum scattering vector q down to 0.0004 Å-1, which allows resolving ordered d-spacing up to 1 µm. A microbeam, of 10-50 µm beam size, is tailored by a combined set of high-heat-load slits followed by micrometre-precision slits situated at the front-end 15.5 m position. The second set of KB mirrors then focus the beam to the 40 m sample position, with a demagnification ratio of ∼1.5. A detecting system comprising two in-vacuum X-ray pixel detectors is installed to perform synchronized small- and wide-angle X-ray scattering data collections. The observed beamline performance proves the feasibility of having compound features of high flux, microbeam and ultra-SAXS in one beamline.

A longitudinal histologic evaluation of vitamin D receptor expression in the skeletal muscles of patients with a distal radius fracture.

We investigated the effect of vitamin D supplementation on the expression of muscle vitamin D receptor (VDR) and cross-sectional area (CSA) in patients with a distal radius fracture (DRF). Significant increases in VDR expression and CSA were observed, especially in vitamin D-deficient patients. PURPOSE: Vitamin D supplementation is known to enhance muscle mass and function, but whether the VDR is essential in this process remains unknown. We evaluated the change in VDR expression and CSA in the forearm muscles following vitamin D supplementation in patients with a DRF. METHODS: We prospectively recruited 18 women with a median age of 63.5 years who have a DRF. We obtained two biopsies of the forearm muscle, first at the time of fracture repair and then during hardware removal. We supplemented 1000 IU of vitamin D per day during a median interval of 8 months. We examined the changes in VDR expression and CSA by immunohistochemistry. RESULTS: The median serum 25-hydroxyvitamin D [25(OH)D] increased from 14.3 to 32.1 ng/mL (P = 0.001). The median VDR expression increased from 0.72 to 0.78 (P = 0.002), and the median CSA increased from 1290.0 to 1685.8 µm2 (P = 0.022). Significant increases in VDR expression and CSA were observed in vitamin D-deficient patients [25(OH)D] < 20 ng/mL, but not in vitamin D-non-deficient patients. The changes in VDR expression and CSA were in the same direction in 13 patients, but in the opposite direction in 5 patients. CONCLUSION: Vitamin D supplementation may increase muscle VDR expression and CSA in patients with a DRF, especially in vitamin D-deficient patients. The increase in CSA without an increase in VDR expression in some patients indicates that the effect of vitamin D supplementation on muscle mass could be mediated by indirect effect of serum vitamin D restoration and by VDR.

Radiological hazard associated with amang processing industry in Peninsular Malaysia and its environmental impacts.

Continuous depletion in tin productions has led to a newly emerging industry that is a tin by-product (amang) processing industry to harness mega tons of tin by-products produced in the past. Amang composed of profitable multi-heavy minerals and rare-earth elements. With poorly established safety and health practices in operating plant, amang poses extremely high radioactivity problem associated with high occupational ionizing radiation exposures to workers and continuously impacting the local environment with radioactive contamination from industrial effluent and solid waste into lithosphere and water bodies. The radioactivity level of 238U and 232Th series in the mineral varies from few hundreds up to ~200,000 and ~400,000 Bq kg-1 respectively and are potential to yield more than ~ 30,000 nGy h-1 of gamma (γ) radiation exposure to plant workers. The study found out that for 8 h of work time, a worker is estimated to receive an average effective dose of 0.1 mSv per day from external γ radiation source with a maximum up to 2 mSv per day for extreme exposure situation. Interferences of different exposure routes for examples inhalation of equivalent equilibrium concentration (ECC) of 222Rn and 220Rn progenies and airborne long-lived α particles from the dusty working environment could pose a higher total effective dose as much as 5 mSv per day and 115 mSv per year. The value is 5 times higher than the annual dose limit for designated radiation worker (20 mSv) in Peninsular Malaysia. The study found that 41% of the total received an effective dose received by a worker is contributed by 222Rn, 32% of airborne particulates and dust, 23% from external γ exposure and 4% from 220Rn. Based on radioecological risk assessment, the study found out that the aquatic environment is the highly exposed group to ionizing radiation from industrial effluent discharge and sand residues. With the impotent establishment of radiation protection in the industry, plus the country newly introduced long-term plan to revive tin mining as well as its accessory amang mineral, it is necessary for the government to harmonize current regulation to improve the worker safety and health as well as sustaining local environment.

Early Bactericidal Activity Trial of Nitazoxanide for Pulmonary Tuberculosis.

This study was conducted in treatment-naive adults with drug-susceptible pulmonary tuberculosis in Port-au-Prince, Haiti, to assess the safety, bactericidal activity, and pharmacokinetics of nitazoxanide (NTZ). This was a prospective phase II clinical trial in 30 adults with pulmonary tuberculosis. Twenty participants received 1 g of NTZ orally twice daily for 14 days. A control group of 10 participants received standard therapy over 14 days. The primary outcome was the change in time to culture positivity (TTP) in an automated liquid culture system. The most common adverse events seen in the NTZ group were gastrointestinal complaints and headache. The mean change in TTP in sputum over 14 days in the NTZ group was 3.2 h ± 22.6 h and was not statistically significant (P = 0.56). The mean change in TTP in the standard therapy group was significantly increased, at 134 h ± 45.2 h (P < 0.0001). The mean NTZ MIC for Mycobacterium tuberculosis isolates was 12.3 µg/ml; the mean NTZ maximum concentration (Cmax) in plasma was 10.2 µg/ml. Negligible NTZ levels were measured in sputum. At the doses used, NTZ did not show bactericidal activity against M. tuberculosis Plasma concentrations of NTZ were below the MIC, and its negligible accumulation in pulmonary sites may explain the lack of bactericidal activity. (This study has been registered at ClinicalTrials.gov under identifier NCT02684240.).

A phase II, multicenter, two cohort study of 160 mg osimertinib in EGFR T790M-positive non-small-cell lung cancer patients with brain metastases or leptomeningeal disease who progressed on prior EGFR TKI therapy.

BACKGROUND: Up to 40% of patients with non-small-cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutations treated with EGFR tyrosine kinase inhibitors (TKIs) present with disease progression in the central nervous system (CNS), either as brain metastases (BM) or leptomeningeal metastases (LM). Osimertinib (80 mg), a third-generation, irreversible, oral EGFR TKI, has shown efficacy in active CNS metastases. However, efficacy of osimertinib 160 mg in BM or LM is unclear. PATIENTS AND METHODS: This prospective, single-arm, two cohort study evaluated the efficacy of osimertinib 160 mg in T790M-positive BM or LM NSCLC patients who progressed on prior EGFR TKI (NCT03257124) treatment. The primary end points were objective response rate (ORR) (H1 = 30%) for the BM cohort and overall survival (OS) (H1 = 5 months) for the LM cohort. RESULTS: The median follow-up duration was 10.1 months and 9.6 months for the BM and LM cohorts, respectively. In the BM cohort, intracranial ORR and disease control rate were 55.0% and 77.5%, respectively. The median progression-free survival (PFS) was 7.6 months [95% confidence interval (CI) 5.0-16.6]; the median OS was 16.9 months [95% CI 7.9-not reached (NR)]. In the LM cohort, intracranial disease control rate was 92.5% and complete response rate was 12.5%. The median OS was 13.3 months (95% CI 9.1-NR); the median PFS was 8.0 months (95% CI 7.2-NR). Subgroup analyses based on previous exposure to T790M-targeting agents, including osimertinib 80 mg or other third-generation EGFR TKIs, showed no difference in PFS in both the BM (n = 18, P = 0.39) and LM (n = 17, P = 0.85) cohorts. Previous radiotherapy favored PFS in the BM cohort (hazard ratio 0.42, P = 0.04). The most common adverse events were decreased appetite, diarrhea, and skin rash; however, most were grade 1-2. CONCLUSION: Thus, osimertinib 160 mg demonstrated promising ORR and survival benefit with a tolerable safety profile in EGFR T790M-positive NSCLC patients with CNS metastasis who progressed on prior EGFR TKIs.

Fibronectin fragment inhibits xylosyltransferase-1 expression by regulating Sp1/Sp3- dependent transcription in articular chondrocytes.

OBJECTIVE: We investigated the effects of 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f) on xylosyltransferase-1 (XT-1), an essential anabolic enzyme that catalyzes the initial and rate-determining step in glycosaminoglycan chain synthesis, in human primary chondrocytes. METHODS: Proteoglycan and XT-1 expression in cartilage tissue was analyzed using safranin O staining and immunohistochemistry. The effects of 29-kDa FN-f on XT-1 expression and its relevant signaling pathway were analyzed by quantitative real-time-PCR, immunoblotting, chromatin immunoprecipitation, and immunoprecipitation assays. The receptors for 29-kDa FN-f were investigated using small interference RNA and blocking antibodies. RESULTS: The expression of XT-1 was significantly lower in human osteoarthritis cartilage than in normal cartilage. Intra-articular injection of 29-kDa FN-f reduced proteoglycan levels and XT-1 expression in murine cartilage. In addition, in 29-kDa FN-f-treated cells, XT-1 expression was significantly suppressed at both the mRNA and protein levels, modulated by the transcription factors specificity protein 1 (Sp1), Sp3, and activator protein 1 (AP-1). The 29-kDa FN-f suppressed the binding of Sp1 to the promoter region of XT-1 and enhanced the binding of Sp3 and AP-1. Inhibition of mitogen-activated protein kinase and nuclear factor kappa B signaling pathways restored the 29-kDa FN-f-inhibited XT-1 expression, along with the altered expression of Sp1 and Sp3. Blockading toll-like receptor 2 (TLR-2) and integrin α5ß1 via siRNA and blocking antibodies revealed that the effects of 29-kDa FN-f on XT-1 expression were mediated through the TLR-2 and integrin α5ß1 signaling pathways. CONCLUSION: These results demonstrate that 29-kDa FN-f negatively affects cartilage anabolism by regulating glycosaminoglycan formation through XT-1.

Search for a Dark Matter-Induced Annual Modulation Signal in NaI(Tl) with the COSINE-100 Experiment.

We present new constraints on the dark matter-induced annual modulation signal using 1.7 years of COSINE-100 data with a total exposure of 97.7 kg yr. The COSINE-100 experiment, consisting of 106 kg of NaI(Tl) target material, is designed to carry out a model-independent test of DAMA/LIBRA's claim of WIMP discovery by searching for the same annual modulation signal using the same NaI(Tl) target. The crystal data show a 2.7 cpd/kg/keV background rate on average in the 2-6 keV energy region of interest. Using a χ-squared minimization method we observe best fit values for modulation amplitude and phase of 0.0092±0.0067 cpd/kg/keV and 127.2±45.9 d, respectively.

First Direct Search for Inelastic Boosted Dark Matter with COSINE-100.

A search for inelastic boosted dark matter (IBDM) using the COSINE-100 detector with 59.5 days of data is presented. This relativistic dark matter is theorized to interact with the target material through inelastic scattering with electrons, creating a heavier state that subsequently produces standard model particles, such as an electron-positron pair. In this study, we search for this electron-positron pair in coincidence with the initially scattered electron as a signature for an IBDM interaction. No excess over the predicted background event rate is observed. Therefore, we present limits on IBDM interactions under various hypotheses, one of which allows us to explore an area of the dark photon parameter space that has not yet been covered by other experiments. This is the first experimental search for IBDM using a terrestrial detector.

White matter hyperintensities and recurrent stroke risk in patients with stroke with small-vessel disease.

BACKGROUND AND PURPOSE: White matter hyperintensities (WMH) are a predictor of stroke among elderly individuals. This study aimed to evaluate the association between WMH severity and the risk of recurrent vascular events among Asian patients with ischaemic stroke with small-vessel disease (SVD) including micro/macrobleeds and lacunes. METHODS: Data from participants (n = 1454) in the PICASSO (PreventIon of CArdiovascular Events in iSchemic Stroke Patients with High Risk of Cerebral HemOrrhage) trial were reviewed. The severity of WMH in baseline brain magnetic resonance imaging scans was assessed using the Fazekas scale. The association between WMH severity and stroke (ischaemic or hemorrhagic) and major vascular events (MVEs) (a composite of stroke/myocardial infarction/vascular death) was assessed. RESULTS: Study patients had a significant burden of SVD: Fazekas score 0 (n = 2), 1 (n = 426), 2 (n = 650) and 3 (n = 376) [median Fazekas score 2 (mean follow-up, 1.9 ± 1.3 years)]. The stroke incidence rate per 100 personyears was 2.6 in the Fazekas 0-1 group, 3.6 in the Fazekas 2 group and 7.0 in the Fazekas 3 group, and the rates for MVEs were 3.3, 4.3 and 7.6, respectively. Compared with the Fazekas 0-1 group, the Fazekas 3 group was associated with a higher risk of stroke [adjusted hazard ratio (HR), 2.15; 95% confidence interval (CI), 1.19-3.88; P = 0.011], ischaemic stroke (adjusted HR, 2.11; 95% CI, 1.07-4.15; P = 0.031), hemorrhagic stroke (adjusted HR, 3.72; 95% CI, 1.09-12.70; P = 0.036) and MVEs (adjusted HR, 2.09; 95% CI, 1.20-3.66; P = 0.010). CONCLUSION: Advanced WMH in Asian patients with ischaemic stroke with SVD burden was associated with an increased risk of recurrent vascular events. It may exert an effect as a prognostic indicator in high risk of recurrent vascular events.

Impact of ledipasvir/sofosbuvir on the work productivity of genotype 1 chronic hepatitis C patients in Asia.

Chronic, untreated hepatitis C virus (HCV) infection is associated with a poor clinical prognosis and a detrimental impact on patients' lives, including on work productivity. To estimate the value of productivity losses due to genotype 1 (GT1) HCV infection in Hong Kong, Singapore, South Korea and Taiwan and to estimate the potential productivity gains associated with treating patients with ledipasvir/sofosbuvir (LDV/SOF) therapy, an economic model was developed with a time horizon of 1 year. Hepatitis C virus patients entered the model at 12 weeks post-treatment, having achieved or not achieved sustained virological response (SVR). Absenteeism and presenteeism rates were taken from a pooled analysis of data from the ION 1-3 studies. These rates were converted into hours of lost productivity, multiplied by the average wage and applied to the total employed, adult GT1 population in each country. Results were compared assuming no treatment, and assuming all patients were treated with LDV/SOF. Total productivity losses due to untreated HCV were: $11.3 million, $17.1 m, $146.0 m and $349.1 m in Hong Kong, Singapore, South Korea and Taiwan. LDV/SOF treatment resulted in economic gains of $4.5 m, $6.8 m, $58.7 m and $138 m, respectively. These gains were due to reduced presenteeism. The results were sensitive to changes in the prevalence of HCV and the average wage. In conclusion, productivity losses due to untreated HCV infection represent a substantial economic burden. By instituting universal HCV treatment with LDV/SOF (or other therapies with high SVR rates), productivity gains can be achieved.

Systemic mastocytosis identified in two women developing fragility fractures during lactation.

Two women presenting with fragility fractures during lactation had bone mineral density (BMD) reduced more greatly than usually associated with lactation. The first woman was 29 years old with a BMD T-score of - 3.2 SD at the spine and- 2.0 SD at the femoral neck. The second woman was 35 years old with a BMD T-score of - 4.5 SD at the spine and - 2.8 SD at the femoral neck. Both women had increased cortical porosity and reduced trabecular density. Investigation identified an elevated serum tryptase, and marrow biopsy confirmed the diagnosis of mastocytosis. Lactation causes bone loss, but the occurrence of fractures in the setting of severe deficits in BMD and microstructural deterioration signals the need to consider additional causes of bone loss.

Locally delivered ethyl-2,5-dihydroxybenzoate using 3D printed bone implant for promotion of bone regeneration in a osteoporotic animal model.

Osteoporosis is a disease characterized by low bone mass, most commonly caused by an increase in bone resorption that is not matched by sufficient bone formation. The most common complications of postmenopausal osteoporosis are bone-related defects and fractures. Fracture healing is a multifactorial bone regeneration process, influenced by both biological and mechanical factors related to age, osteoporosis and stability of the osteosynthesis. During the treatment of bone defects in osteoporotic conditions, imbalanced bone remodeling is the leading cause for implant failure. To overcome these problems, ethyl-2,5-dihydroxybenzoate (E-2,5-DHB), a drug that promotes bone formation and inhibits bone resorption, was used. E-2,5-DHB-incorporating titanium (Ti) implants using poly(lactic-co-glycolic acid) (PLGA) coating for local delivery of E-2,5-DHB were developed and the effects on bone healing of femoral defects were evaluated in an osteoporotic model. The release of E-2,5-DHB resulted in decreased bone resorption and increased bone formation around the implant. Thus, it was confirmed that, in the osteoporotic model, bone healing was increased and implant fixation was enhanced. These results suggested that E-2,5-DHB-coated Ti implants have great potential as an ultimate local drug delivery system for bone tissue scaffolds.

Factors affecting quality of life in patients with vitiligo: a nationwide study.

BACKGROUND: Little is known about factors affecting the quality of life (QoL) of patients with vitiligo, and previous studies have shown conflicting results. OBJECTIVES: To explore the QoL of patients with vitiligo and to identify factors affecting QoL. METHODS: A nationwide questionnaire-based study was conducted with 1123 patients with vitiligo recruited from 21 hospitals in Korea from July 2015 to June 2016. Data were collected using a structured questionnaire for demographic information and the Skindex-29 instrument. Mild or severely impaired QoL in patients with vitiligo was assessed according to each domain (symptoms, functioning and emotions) of Skindex-29. Multivariate logistic regression analyses were performed to determine the factors associated with QoL. RESULTS: Of the enrolled participants, 609 were male and 514 female, with a mean age of 49·8 years (range 20-84). The median duration of disease was 3·0 years (range 0-60). Using multivariate logistic regression modelling, the involvement of visible body parts and a larger affected body surface area were consistently associated with QoL impairment in all three domains of Skindex-29. Additionally, the QoL of patients aged 20-59 years, who potentially had a more active social life than older patients, was associated with functional impairment. Furthermore, a higher educational background was associated with emotional impairment. CONCLUSIONS: A multitude of factors significantly influence the QoL of patients with vitiligo. A better appreciation of these factors would help the management of these patients.