Nasopharyngeal lymphatic plexus is a hub for cerebrospinal fluid drainage.

Cerebrospinal fluid (CSF) in the subarachnoid space around the brain has long been known to drain through the lymphatics to cervical lymph nodes1-17, but the connections and regulation have been challenging to identify. Here, using fluorescent CSF tracers in Prox1-GFP lymphatic reporter mice18, we found that the nasopharyngeal lymphatic plexus is a major hub for CSF outflow to deep cervical lymph nodes. This plexus had unusual valves and short lymphangions but no smooth-muscle coverage, whereas downstream deep cervical lymphatics had typical semilunar valves, long lymphangions and smooth muscle coverage that transported CSF to the deep cervical lymph nodes. α-Adrenergic and nitric oxide signalling in the smooth muscle cells regulated CSF drainage through the transport properties of deep cervical lymphatics. During ageing, the nasopharyngeal lymphatic plexus atrophied, but deep cervical lymphatics were not similarly altered, and CSF outflow could still be increased by adrenergic or nitric oxide signalling. Single-cell analysis of gene expression in lymphatic endothelial cells of the nasopharyngeal plexus of aged mice revealed increased type I interferon signalling and other inflammatory cytokines. The importance of evidence for the nasopharyngeal lymphatic plexus functioning as a CSF outflow hub is highlighted by its regression during ageing. Yet, the ageing-resistant pharmacological activation of deep cervical lymphatic transport towards lymph nodes can still increase CSF outflow, offering an approach for augmenting CSF clearance in age-related neurological conditions in which greater efflux would be beneficial.

The safety and immunogenicity of a bivalent conjugate vaccine against Salmonella enterica Typhi and Paratyphi A in healthy Indian adults: a phase 1, randomised, active-controlled, double-blind trial.

BACKGROUND: Enteric fever caused by Salmonella enterica Typhi and Salmonella Paratyphi A is an important public health problem, especially in low-income and middle-income countries with limited access to safe water and sanitation. We present results from, to our knowledge, the first ever human study of a bivalent paratyphoid A-typhoid conjugate vaccine (Sii-PTCV). METHODS: In this double-blind phase 1 study, 60 healthy Indian adults were randomly assigned (1:1) to receive a single intramuscular dose of either Sii-PTCV or typhoid conjugate vaccine (Typbar-TCV). Safety was assessed by observing solicited adverse events for 1 week, unsolicited events for 1 month, and serious adverse events (SAEs) over 6 months. Immunogenicity at 1 month and 6 months was assessed by measuring anti-capsular polysaccharide antigen Vi (anti-Vi) IgG and IgA against Salmonella Typhi and anti-lipopolysaccharide (LPS) IgG against Salmonella Paratyphi A by ELISA, and functional antibodies using serum bactericidal assay (SBA) against Salmonella Paratyphi A. This study is registered with Clinical Trial Registry-India (CTRI/2022/06/043608) and is completed. FINDINGS: 60 participants were enrolled. Of these 60 participants, 57 (95%) participants were male and three (5%) participants were female. Solicited adverse events were observed in 27 (90%) of 30 participants who received Sii-PTCV and 26 (87%) of 30 participants who received Typbar-TCV. The most common local solicited event was pain in 27 (90%) participants who received Sii-PTCV and in 23 (77%) participants who received Typbar-TCV. The most common solicited systemic event was myalgia in five (17%) participants who received Sii-PTCV, whereas four (13%) participants who received Typbar-TCV had myalgia and four (13%) had headache. No vaccine-related unsolicited adverse events or SAEs were reported. The seroconversion rates on day 29 were 96·7% (95% CI 82·8-99·9) with Sii-PTCV and 100·0% (88·4-100·0) with Typbar-TCV for anti-Vi IgG; 93·3% (77·9-99·2) with Sii-PTCV and 100·0% (88·4-100·0) with Typbar-TCV for anti-Vi IgA; 100·0% (88·4-100·0) with Sii-PTCV and 3·3% (0·1-17·2) with Typbar-TCV for anti-LPS (paratyphoid); and 93·3% (77·9-99·2) with Sii-PTCV and 0% (0·0-11·6) with Typbar-TCV for SBA titres (paratyphoid). Paratyphoid anti-LPS immune responses were sustained at day 181. INTERPRETATION: Sii-PTCV was safe and immunogenic for both typhoid and paratyphoid antigens indicating its potential for providing comprehensive protection against enteric fever. FUNDING: Serum Institute of India.

5-year vaccine protection following a single dose of Vi-tetanus toxoid conjugate vaccine in Bangladeshi children (TyVOID): a cluster randomised trial.

BACKGROUND: WHO currently recommends a single dose of typhoid conjugate vaccine (TCV) in high-burden countries based on 2-year vaccine efficacy data from large randomised controlled trials. Given the decay of immunogenicity, the protection beyond 2 years is unknown. We therefore extended the follow-up of the TyVAC trial in Bangladesh to assess waning of vaccine protection to 5 years after vaccination. METHODS: We conducted a cluster randomised controlled trial (TyVAC; ISRCTN11643110) in Dhaka, Bangladesh, between 2018 and 2021. Children aged 9 months to 15 years were invited to receive a single dose of TCV or Japanese encephalitis vaccine between April 15, 2018, and November 16, 2019, based on the randomisation of their clusters of residence. Children who received the Japanese encephalitis vaccine were invited to receive TCV at the final visit between Jan 6, and Aug 31, 2021, according to the protocol. This follow-on study extended the follow-up of the original trial until Aug 14, 2023. The primary endpoint of this study was to compare the incidence of blood culture-confirmed typhoid between children who received TCV in 2018-19 (the previous-TCV group) and those who received the vaccine in 2021 (the recent-TCV group), to evaluate the relative decline in vaccine protection. We also did a nested study using the test-negative design comparing the recent-TCV and previous-TCV groups with unvaccinated individuals, as well as an immunogenicity study in a subset of 1500 children. FINDINGS: Compared with the recent-TCV group, the previous-TCV group had an increased risk of typhoid fever between 2021-23, with an adjusted incidence rate ratio of 3·10 (95% CI 1·53 to 6·29; p<0·0001), indicating a decline in the protection of a single-dose of TCV 3-5 years after vaccination. The extrapolated vaccine effectiveness in years 3-5 was 50% (95% CI -13 to 78), and was validated using the test-negative design analysis, with a vaccine effectiveness of 84% (74 to 90) in the recent-TCV group and 55% (36 to 68) in the previous-TCV group, compared with unvaccinated individuals. Anti-Vi-IgG responses declined over the study period. The highest rate of decay was seen in children vaccinated at younger than 2 years in the original trial. The inverse correlation between age and the decay of antibodies was also seen in the subgroup analysis of vaccine effectiveness, where the youngest age group (<7 years at fever visits) exhibited the fastest waning, with vaccine effectiveness dropping to 24% (95% CI -29 to 55) at 3-5 years after vaccination. INTERPRETATION: A decline in the protection conferred by a single-dose TCV was observed 3-5 years after vaccination, with the greatest decline in protection and immune responses observed in children vaccinated at younger ages. A booster dose of TCV around school entry age might be needed for children vaccinated while younger than 2 years to sustain protection against typhoid fever during the school years when the risk is the highest. FUNDING: The Bill & Melinda Gates Foundation.

Human papillomavirus detection rates in Bowen disease: correlation with pelvic and digital region involvement and specific p53 immunostaining patterns.

BACKGROUND: The relationship between human papillomavirus (HPV) and Bowen disease (BD) is not fully understood. OBJECTIVES: To investigate the differences in HPV detection rates in BD samples across various body regions and analyse the expression patterns of p53, p16 and Ki-67 in relation to HPV presence. METHODS: Tissue samples from patients diagnosed with BD, confirmed through histopathology, were retrospectively collected. Next-generation sequencing was used for HPV DNA detection. Immunohistochemistry (IHC) for p16, p53 and Ki-67 was performed. RESULTS: Out of 109 patients with BD, 21 (19.3%) were HPV-positive. All identified types were α-HPVs, with HPV-16 being the most common. The HPV detection rate was significantly higher in the pelvic (9/13, 69%, P < 0.001) and digital (5/10, 50%, P = 0.02) areas compared with those in the other regions. HPV presence was significantly correlated with p53 negativity (P = 0.002), the p53 'non-overexpression' IHC pattern (P < 0.001) and p16-p53 immunostain pattern discordance (P < 0.001). Conversely, there was no notable association between HPV presence and p16 positivity, the p16 IHC pattern or Ki-67 expression. CONCLUSIONS: Our findings suggest the oncogenic role of sexually transmitted and genito-digitally transmitted α-HPVs in the pathogenesis of BD in pelvic and digital regions.

Characterization of Codeine Treatment Responders Among Patients with Refractory or Unexplained Chronic Cough: A Prospective Real-World Cohort Study.

PURPOSE: Codeine is a narcotic antitussive often considered for managing patients with refractory or unexplained chronic cough. This study aimed to evaluate the proportion and characteristics of patients who responded to codeine treatment in real-world practice. METHODS: Data from the Korean Chronic Cough Registry, a multicenter prospective cohort study, were analyzed. Physicians assessed the response to codeine based on the timing and degree of improvement after treatment initiation. Follow-up assessments included the Leicester Cough Questionnaire and cough severity visual analog scale at six months. In a subset of subjects, objective cough frequency was evaluated following the initiation of codeine treatment. RESULTS: Of 305 patients, 124 (40.7%) responded to treatments based on anatomic diagnostic protocols, while 181 (59.3%) remained unexplained or refractory to etiological treatments. Fifty-one subjects (16.7%) were classified as codeine treatment responders (those showing a rapid and clear response), 57 (18.7%) as partial responders, and 62 (20.3%) as non-responders. Codeine responders showed rapid improvement in objective cough frequency and severity scores within a week of the treatment. At 6 months, responders showed significantly improved scores in cough scores, compared to non-responders. Several baseline parameters were associated with a more favorable treatment response, including older age, non-productive cough, and the absence of heartburn. CONCLUSIONS: Approximately 60% of chronic cough patients in specialist clinics may require antitussive drugs. While codeine benefits some, only a limited proportion (about 20%) of patients may experience rapid and significant improvement. This underscores the urgent need for new antitussive drugs to address these unmet clinical needs.

Ultrasonographic analysis of facial skin thickness in relation to age, site, sex, and body mass index.

BACKGROUND: Numerous nonsurgical but invasive cosmetic procedures are performed blindly in the dermis or subcutaneous fat layer of the facial skin. OBJECTIVES: To measure the numerical skin thickness of the facial areas where dermatological procedures are performed by applying ultrasound techniques, and to make it possible to estimate the skin thickness by investigating the influence of several individual constitutional factors such as age, sex, and body mass index (BMI), so that these variables can be applied to estimate skin thickness. MATERIALS AND METHODS: Skin thickness was measured at eight different facial points using an ultrasound machine (Affiniti 50; Philips Inc.). Demographic data were gathered using questionnaires. Manual BMI was calculated from the weight and height of each participant, and individual BMI measurements were performed using a body composition analyzer. RESULTS: In terms of whole skin thickness, the thickest point was the mouth corner, and the thinnest point was the lateral forehead. The thickest point in the epidermis was the chin, and the thinnest point was the nasolabial fold. The thickest point in the dermis was the corner of the mouth, and the thinnest was the lateral forehead. Full skin thickness and dermal thickness were mostly lower in females. Skin thickness was not significantly correlated with BMI. CONCLUSION: The skin thickness at different points on the face was variable, and realistic data about skin thickness can be obtained by in vivo ultrasonographic analysis of the skin.

Effect of Previous Caudal Block to Predict Successful Outcome after Adhesiolysis using a Steerable Catheter in Lumbar Failed Back Surgery Syndrome: A Retrospective Study.

Adhesiolysis is minimally invasive and commonly used for pain associated with adhesion after lumbar spine surgery. Caudal epidural block may be used for radiating pain due to failed back surgery syndrome. We evaluated the predictive value of response to caudal block performed prior to adhesiolysis in failed back surgery syndrome. Between January 1, 2013 and June 30, 2020, 150 patients with failed back surgery syndrome were treated with adhesiolysis using a steerable catheter at the pain clinic of a tertiary hospital after failed conservative treatment (including caudal block). Patient demographics, pain duration, and lumbar magnetic resonance imaging findings were examined. Response to previous caudal block was determined as a binary result (yes or no). Patients were followed up 3 months after adhesiolysis. Successful outcome was defined as a ≥2-point reduction in the numeric rating scale scores for radicular pain 3 months after adhesiolysis, evident in 81/150 (46%) patients. Multivariable logistic regression analysis revealed that caudal block response was an independent predictor of successful adhesiolysis (odds ratio = 4.403; p = 0.015). Response to prior caudal block is a positive predictor of successful adhesiolysis.

Development of Viral-Vectored Vaccines and Virus Replicon Particle-Based Neutralisation Assay against Mayaro Virus.

Mayaro virus (MAYV) is an emerging alphavirus causing acute febrile illness associated with chronic polyarthralgia. Although MAYV is currently restricted to tropical regions in South America around the Amazon basin, it has the potential to spread globally by Aedes species mosquitoes. In addition, there are currently no specific therapeutics or licenced vaccines against MAYV infection. We have previously shown that an adenovirus based Mayaro vaccine (ChAdOx1 May) was able to provide full protection against MAYV challenge in vaccinated A129 mice and induced high neutralising antibody titres. In this study, we have constructed a replication deficient simian adenovirus (ChAdOx2) and a Modified Ankara Virus (MVA) based vaccine expressing the MAYV structural cassette (sMAYV) similar to ChAdOx1 May, and characterised recombinant MAYV E2 glycoprotein expressed in a mammalian system for immune monitoring. We demonstrate that ChAdOx2 May was able to induce high antibody titres similar to ChAdOx1 May, and MVA May was shown to be an effective boosting strategy following prime vaccination with ChAdOx1 or ChAdOx2 May. In order to measure MAYV neutralising ability, we have developed a virus replicon particle-based neutralisation assay which effectively detected neutralising antibodies against MAYV. In summary, our study indicates the potential for further clinical development of the viral vectored MAYV vaccines against MAYV infections.

The tumor necrosis factor family molecules LIGHT and lymphotoxins in sinus mucosa of patients with chronic rhinosinusitis with or without nasal polyps.

BACKGROUND: Little is known about the role of lymphotoxins (LTs) family in the sinonasal mucosa of patients with chronic rhinosinusitis (CRS). This study aims at investigating the expression of LIGHT, LTα, LTß, and their receptors, LTßR and HVEM in normal and inflammatory sinus mucosa, and the effect of LIGHT and LTalpha1beta2 on chemokine secretion in epithelial cells, epithelial permeability, and leukocyte migration. MATERIAL AND METHODS: The expression of LTs family in sinonasal mucosa was evaluated with real-time PCR, immunohistochemistry, and western blot. In LTßR, HVEM siRNA, or control siRNA-transfected epithelial cells treated with LIGHT or LTalpha1beta2, the expression of chemokines, the epithelial permeability, and the expression of junctional complex proteins were evaluated using real-time PCR, ELISA, western blot, confocal microscopy, and FITC-dextran. In cultured endothelial cells treated with LIGHT or LTalpha1beta2, the expression of ICAM-1 and VCAM-1, and leukocyte migration were elucidated. RESULTS: LTs family was expressed in normal mucosa and their levels were increased in inflammatory mucosa of CRS patients. Recombinant LIGHT and LTalpha1beta2 induced chemokine secretion, increased epithelial permeability, and promoted leukocyte migration. However, the activity of LIGHT and LTalpha1beta2 was attenuated in cells transfected with LTßR and HVEM siRNA. CONCLUSIONS: LIGHT and LTs may participate in the ongoing process of chronic inflammation, inducing chemokine secretion, leukocyte migration, and dysregulated epithelial barrier through LTßR and HVEM in sinonasal mucosa.

Asymmetric Total Synthesis of Oxazolomycins B and C.

Efforts towards the first total synthesis of (-)-oxazolomycin B and (+)-oxazolomycin C from the intermediate of our previous synthesis of (+)-neoxazolomycin are reported. The syntheses were achieved in a longest linear sequence of 25 steps from the amino acid serine in 3.6 and 2.7 % overall yields, respectively. The efficiency of our approach is derived from silyl triflate-mediated reductive oxazolidine ring-opening and Fürstner's Ru-catalyzed hydrosilylation and protodesilylation reactions. The obtained spectra and optical rotations were in good agreement with those of natural products, thus confirming the structures.

Toll-like receptor mediated inflammation requires FASN-dependent MYD88 palmitoylation.

Toll-like receptor (TLR)/myeloid differentiation primary response protein (MYD88) signaling aggravates sepsis by impairing neutrophil migration to infection sites. However, the role of intracellular fatty acids in TLR/MYD88 signaling is unclear. Here, inhibition of fatty acid synthase by C75 improved neutrophil chemotaxis and increased the survival of mice with sepsis in cecal ligation puncture and lipopolysaccharide-induced septic shock models. C75 specifically blocked TLR/MYD88 signaling in neutrophils. Treatment with GSK2194069 that targets a different domain of fatty acid synthase, did not block TLR signaling or MYD88 palmitoylation. De novo fatty acid synthesis and CD36-mediated exogenous fatty acid incorporation contributed to MYD88 palmitoylation. The binding of IRAK4 to the MYD88 intermediate domain and downstream signal activation required MYD88 palmitoylation at cysteine 113. MYD88 was palmitoylated by ZDHHC6, and ZDHHC6 knockdown decreased MYD88 palmitoylation and TLR/MYD88 activation upon lipopolysaccharide stimulus. Thus, intracellular saturated fatty acid-dependent palmitoylation of MYD88 by ZDHHC6 is a therapeutic target of sepsis.

Transglutaminase 2 mediates lung inflammation and remodeling by transforming growth factor beta 1 via alveolar macrophage modulation.

Transforming growth factor beta 1 (TGF-ß1) induces pulmonary fibrosis by enhancing epithelial apoptosis and affects the enzymatic activity of transglutaminase 2 (TG2). The aim of this study was to determine the role of TG2 in TGF-ß1-induced lung remodeling and alveolar macrophage modulation. We characterized the in vivo effects of TGF-ß1 and TG2 on lung inflammation, fibrosis, and macrophage activity using transgenic C57BL/6 mice with wild and null TG2 loci. The effect of TG2 inhibition on in vitro TGF-ß1-stimulated alveolar macrophages was assessed through mRNA analysis. TG2 was remarkably upregulated in the lungs of TGF-ß1 transgenic (TGF-ß1 Tg) mice, especially in alveolar macrophages and epithelial cells. In the absence of TG2, TGF-ß1-induced inflammation was suppressed, decreasing the number of macrophages in the bronchoalveolar lavage fluid. In addition, the alveolar destruction and peribronchial fibrosis induced by TGF-ß1 overexpression were significantly reduced, which correlated with decreases in the expression of fibroblast growth factor and matrix metallopeptidase 12, respectively. However, TG2 deficiency did not compromise the phagocytic activity of alveolar macrophages in TGF-ß1 Tg mice. At the same time, TG2 contributed to the regulation of TGF-ß1-induced macrophage activation. Inhibition of TG2 did not affect the TGF-ß1-induced expression of CD86, an M1 marker, in macrophages, but it did reverse the TGF-ß1-induced expression of CD206. This result suggests that TG2 mediates TGF-ß1-induced M2-like polarization but does not contribute to TGF-ß1-induced M1 polarization. In conclusion, TG2 regulates macrophage modulation and plays an important role in TGF-ß1-induced lung inflammation, destruction, and fibrosis.

Compositional engineering of perovskite materials for high-performance solar cells.

Of the many materials and methodologies aimed at producing low-cost, efficient photovoltaic cells, inorganic-organic lead halide perovskite materials appear particularly promising for next-generation solar devices owing to their high power conversion efficiency. The highest efficiencies reported for perovskite solar cells so far have been obtained mainly with methylammonium lead halide materials. Here we combine the promising-owing to its comparatively narrow bandgap-but relatively unstable formamidinium lead iodide (FAPbI3) with methylammonium lead bromide (MAPbBr3) as the light-harvesting unit in a bilayer solar-cell architecture. We investigated phase stability, morphology of the perovskite layer, hysteresis in current-voltage characteristics, and overall performance as a function of chemical composition. Our results show that incorporation of MAPbBr3 into FAPbI3 stabilizes the perovskite phase of FAPbI3 and improves the power conversion efficiency of the solar cell to more than 18 per cent under a standard illumination of 100 milliwatts per square centimetre. These findings further emphasize the versatility and performance potential of inorganic-organic lead halide perovskite materials for photovoltaic applications.

Effects of lowest-dose vs. highest-dose pitavastatin on coronary neointimal hyperplasia at 12-month follow-up in type 2 diabetic patients with non-ST elevation acute coronary syndrome: an optical coherence tomography analysis.

Current ACC/AHA guidelines recommend high-dose statin therapy after coronary stenting, especially in diabetic patients; however, pitavastatin 4 mg or pitavastatin 1 mg are frequently used after coronary stenting in Asia, even in patients with acute coronary syndrome. We compared the effects of highest-dose and lowest-dose pitavastatin therapy on coronary neointimal hyperplasia at 12-month follow-up in diabetic patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) using optical coherence tomography. A total of 72 diabetic patients with NSTE-ACS were randomized to lowest-dose pitavastatin [1 mg (n = 36)] or highest-dose pitavastatin [4 mg (n = 36)] after everolimus-eluting stent implantation. The primary endpoint was to compare the normalized neointimal volume at 12-month follow-up. Normalized neointimal volume was significantly lower in the pitavastatin 4 mg group (4.00 ± 2.80 vs. 8.24 ± 2.83 mm3/mm, p < 0.01) at 12-month follow-up. There was also significant difference in neointimal area between the pitavastatin 4 mg group and pitavastatin 1 mg group (0.41 ± 0.28 vs. 0.74 ± 0.23 mm2, p < 0.01). Improvement of brachial artery flow-mediated dilation (baFMD) was significantly higher in the pitavastatin 4 mg group than in pitavastatin 1 mg group (0.15 ± 0.15 vs. - 0.03 ± 0.19 mm, p < 0.001). In addition, the improvement of adiponectin levels was significantly greater in the pitavastatin 4 mg group than in the pitavastatin 1 mg group (2.97 ± 3.98 vs. 0.59 ± 2.80 µg/mL, p < 0.05). Pitavastatin 4 mg significantly improved inflammatory cytokines and lipid profiles compared to pitavastatin 1 mg during the 12-month follow-up, contributing to the reduction of neointimal hyperplasia and to the improvement of baFMD in diabetic patients with NSTE-ACS requiring coronary stenting. Thus, the administration of pitavastatin 4 mg can be safely and effectively used in high-risk patients requiring coronary stenting. Trial registration NCT02545231 (Clinical Trial registration information: https://clinicaltrials.gov/ct2/show/NCT02545231 ).

Increased epicardial adipose tissue thickness is a predictor of new-onset diabetes mellitus in patients with coronary artery disease treated with high-intensity statins.

BACKGROUND: Statins are widely used for lipid lowering in patients with coronary artery disease (CAD), but increasing evidence indicates an association between statin use and new-onset of diabetes mellitus (NODM). Epicardial adipose tissue (EAT) refers to the visceral fat surrounding the heart, which is associated with metabolic diseases. We sought to determine the association between EAT thickness and NODM in CAD patients treated with high-intensity statins. METHODS: We conducted a retrospective medical record review of CAD patients treated with high-intensity statins for at least 6 months after percutaneous coronary intervention performed between January 2009 and June 2013 at Seoul National University Bundang Hospital. EAT thickness was measured by echocardiography using standardized methods. RESULTS: A total of 321 patients were enrolled, who received high-intensity statins for a mean of 952 days; atorvastatin 40 mg in 204 patients (63.6%), atorvastatin 80 mg in 57 patients (17.8%), and rosuvastatin 20 mg in 60 patients (18.7%). During the follow-up period of 3.9 ± 1.7 years, NODM occurred in 40 patients (12.5%). On Cox proportional-hazard regression analysis, EAT thickness at systole [for each 1 mm: hazard ratio (HR) 1.580; 95% confidence interval (CI) 1.346-1.854; P < 0.001] and prediabetes at baseline (HR 4.321; 95% CI 1.998-9.349; P < 0.001) were the only independent predictors of NODM. Using binary cutoff values derived from the receiver operating characteristic curve analysis, EAT thickness at systole larger than 5.0 mm had an HR of 3.402 (95% CI 1.751-6.611, P < 0.001), sensitivity of 52.5%, and specificity of 80.8% for predicting NODM. Also, patients with EAT thickness ≥ 5 mm and prediabetes at baseline had a 12.0-times higher risk of developing NODM compared to the risk noted in patients with EAT thickness < 5 mm and normal glucose tolerance at baseline. CONCLUSION: Epicardial adipose tissue thickness at systole is a consistent independent predictor of NODM in patients with CAD treated with high-intensity statins. Such predictors may help physicians plan adequate surveillance for early detection of NODM.

Optimization of Zika virus envelope protein production for ELISA and correlation of antibody titers with virus neutralization in Mexican patients from an arbovirus endemic region.

BACKGROUND: Zika virus (ZIKV) has become a global threat with immediate need for accurate diagnostics, efficacious vaccines and therapeutics. Several ZIKV envelope (Env)-based vaccines have been developed recently. However, many commercially available ZIKV Env are based on the African lineage and produced in insect cells. Here, we sought to produce Asian-lineage ZIKV Env in mammalian cells for research and clinical applications. METHODS: We designed various gene expression constructs to optimize the production of ZIKV using prM-Env and full or C-terminal truncations of Env; with or without a rat CD4 fusion partner to allow large-scale production of soluble protein in mammalian HEK293 cells. Protein expression was verified by mass spectrometry and western-blot with a pan-flavivirus antibody, a ZIKV Env monoclonal antibody and with immune sera from adenoviral (ChAdOx1) ZIKV Env-vaccinated mice. The resulting Env-CD4 was used as a coating reagent for immunoassay (ELISA) using both mouse and human seropositive sera. RESULTS: Replacement of the C-terminus transmembrane Env domain by a rat CD4 and addition of prM supported optimal expression and secretion of Env. Binding between the antigens and the antibodies was similar to binding when using commercially available ZIKV Env reagents. Furthermore, antibodies from ZIKV patients bound ZIKV Env-CD4 in ELISA assays, whereas sera from healthy blood donors yielded minimal OD background. The serological outcomes of this assay correlated also with ZIKV neutralisation capacity in vitro. CONCLUSIONS: Results obtained from this study indicate the potential of the Asian-lineage Zika Env-CD4 and Env proteins in ELISA assays to monitor humoral immune responses in upcoming clinical trials as well as a sero-diagnostic tool in ZIKV infection.

Age-related prevalence of chronic rhinosinusitis and nasal polyps and their relationships with asthma onset.

BACKGROUND: Chronic rhinosinusitis (CRS) is a major disease condition with high morbidity and can influence lower airway disease status in adults. However, its associations with adult asthma onset and activity have not been examined in detail in a general adult population. OBJECTIVE: To investigate relationships between CRS with nasal polyps (CRSwNP) and asthma characteristics. METHODS: A cross-sectional data set of 17,506 adult participants (≥18 years old) in the Korean National Health and Nutrition Examination Survey from 2010 through 2012 was analyzed. CRS was defined using structured questionnaires according to the international guideline, and presence of nasal polyps was objectively assessed using nasal endoscopy. Presence of asthma and its onset and current activity were assessed using structured questionnaires. RESULTS: CRS was significantly related to asthma, but the relationships were distinct by CRS and asthma status. CRSwNP was significantly associated with adult-onset asthma (onset after 18 years of age) or late-onset asthma (onset after 40 years of age), whereas CRS without nasal polyps was related to childhood-onset asthma (onset before 18 years) or early-onset asthma (onset before 40 years) in adults. The 2 CRS subgroups showed significant associations with current asthma but not with past asthma. However, the comorbid asthma rate was lower than 10% among subjects with CRS. CONCLUSION: This study found distinct age-related patterns of CRSwNP and asthma and demonstrated their significant associations in a general population. However, the low prevalence of asthma in CRSwNP is in sharp contrast to findings in Western populations, which warrants further investigation for ethnic or regional differences in relationships between CRSwNP and asthma.

Open-wedge high tibial osteotomy versus unicompartmental knee arthroplasty: no difference in progression of patellofemoral joint arthritis.

PURPOSE: The purpose of this retrospective comparative study was to evaluate and compare, radiographically and clinically, progression of osteoarthritis (OA) in the patellofemoral (PF) compartment after open-wedge high tibial osteotomy (OWHTO), and unicompartmental knee arthroplasty (UKA) over a minimum follow-up of 5 years. METHODS: In this study, 42 knees in an OWHTO group were compared with 59 knees in a UKA group in terms of radiographic parameters, such as the grading system for OA progression in the PF compartment, and clinical parameters, such as the PF pain and function scores over a minimum follow-up of 5 years. RESULTS: There was no significant difference of OA progression in the PF compartment between the two groups on knee radiography. Compared with the preoperative grades, the UKA group showed significant progression of OA in the medial PF compartment at the final follow-up, whereas the medial PF compartment showed significant stepwise progression by only one grade when compared to the OWHTO group. The PF pain and function scores showed no statistical differences between the two groups at the final follow-up, regardless of OA progression. CONCLUSIONS: There was no significant difference between OWHTO and UKA in terms of progression of OA in the PF compartment or deterioration of PF function score over a minimum follow-up of 5 years. However, the medial PF compartment of the UKA group was minimal, and worsened or progressed by only one grade. LEVEL OF EVIDENCE: III.

An estimation framework for building information modeling (BIM)-based demolition waste by type.

Most existing studies on demolition waste (DW) quantification do not have an official standard to estimate the amount and type of DW. Therefore, there are limitations in the existing literature for estimating DW with a consistent classification system. Building information modeling (BIM) is a technology that can generate and manage all the information required during the life cycle of a building, from design to demolition. Nevertheless, there has been a lack of research regarding its application to the demolition stage of a building. For an effective waste management plan, the estimation of the type and volume of DW should begin from the building design stage. However, the lack of tools hinders an early estimation. This study proposes a BIM-based framework that estimates DW in the early design stages, to achieve an effective and streamlined planning, processing, and management. Specifically, the input of construction materials in the Korean construction classification system and those in the BIM library were matched. Based on this matching integration, the estimates of DW by type were calculated by applying the weight/unit volume factors and the rates of DW volume change. To verify the framework, its operation was demonstrated by means of an actual BIM modeling and by comparing its results with those available in the literature. This study is expected to contribute not only to the estimation of DW at the building level, but also to the automated estimation of DW at the district level.