Cells resident to precision templated 40-µm pore scaffolds generate small extracellular vesicles that affect CD4+ T cell phenotypes through regulatory TLR4 signaling.

Precision porous templated scaffolds (PTS) are a hydrogel construct of uniformly sized interconnected spherical pores that induce a pro-healing response (reducing the foreign body reaction, FBR) exclusively when the pores are 30-40µm in diameter. Our previous work demonstrated the necessity of Tregs in the maintenance of PTS pore size specific differences in CD4+ T cell phenotype. Work here characterizes the role of Tregs in the responses to implanted 40µm and 100µm PTS using WT and FoxP3+ cell (Treg) depleted mice. Proteomic analyses indicate that integrin signaling, monocytes/macrophages, cytoskeletal remodeling, inflammatory cues, and vesicule endocytosis may participate in Treg activation and the CD4+ T cell equilibrium modulated by PTS resident cell-derived small extracellular vesicles (sEVs). The role of MyD88-dependent and MyD88-independent TLR4 activation in PTS cell-derived sEV-to-T cell signaling is quantified by treating WT, TLR4ko, and MyD88ko splenic T cells with PTS cell-derived sEVs. STAT3 and mTOR are identified as mechanisms for further study for pore-size dependent PTS cell-derived sEV-to-T cell signaling. STATEMENT OF SIGNIFICANCE: Unique cell populations colonizing only within 40µm pore size PTS generate sEVs that resolve inflammation by modifying CD4+ T cell phenotypes through TLR4 signaling.

Biomechanical comparison of metal wire and FiberWire as tension band techniques: an ex vivo study.

BACKGROUND: The pin and tension band wire (PTBW) technique is used to convert the tensile force at the olecranon fracture site. Although metal wire can be used for the tension band technique, it has side effects such as skin irritation or infection. Other fixation materials like a high-strength polyester and polyethylene suture that do not cause skin irritation and pain, provide similar mechanical strength. AIMS: The aim of this study was to compare olecranon fragment stability by applying tension bands using metal wire and FiberWire of identical tensile strength. METHODS: This study was designed as ex vivo biomechanical test on canine cadaveric elbows. We biomechanically analyzed the following two fixation methods in cadaveric elbows with olecranon osteotomies: (1) Kirschner (K) wire with 0.76 mm metal wire tension band, (2) K-wires with No. 2 FiberWire tension band. A tensile testing machine was used to measure displacement. RESULTS: It was measured that the mean maximum load (MML) value and mean yield load (MYL) were higher using No. 2 FiberWire as a tension band than 0.76 mm metal wire. CONCLUSION: Biomechanical strength of No. 2 FiberWire was significantly different from 0.76 mm metal wire in a canine model of olecranon osteotomy. So, FiberWire is applicable instead of metal wire that has a similar strength.

Computer Assisted Planning for Curved Laser Interstitial Thermal Therapy.

Laser interstitial thermal therapy (LiTT) isa minimally invasive alternative to conventional open surgery for drug-resistant focal mesial temporal lobe epilepsy (MTLE). Recent studies suggest that higher seizure freedom rates are correlated with maximal ablation of the mesialhippocampal head, whilst sparing of the parahippocampal gyrus (PHG) may reduce neuropsychological sequelae. Current commercially available laser catheters are inserted following manually planned straight-line trajectories, which cannot conform to curved brain structures, such as the hippocampus, without causing collateral damage or requiring multiple insertions. OBJECTIVES: The clinical feasibility and potential of curved LiTT trajectories through steerable needles has yet to be investigated. This is the focus of our work. METHODS: We propose a GPU-accelerated computer-assisted planning (CAP) algorithm for steerable needle insertions that generates optimized curved 3D trajectories with maximal ablation of the amygdalohippocampal complex and minimal collateral damage to nearby structures, while accounting for a variable ablation diameter ( 5-15 mm). RESULTS: Simulated trajectories and ablations were performed on 5 patients with mesial temporal sclerosis (MTS), which were identified from a prospectively managed database. The algorithm generated obstacle-free paths with significantly greater target area ablation coverage and lower PHG ablation variance compared to straight line trajectories. CONCLUSIONS: The presented CAP algorithm returns increased ablation of the amygdalohippocampal complex, with lower patient risk scores compared to straight-line trajectories. SIGNIFICANCE: This is the first clinical application of preoperative planning for steerable needle based LiTT. This study suggests that steerableneedles have the potential to improve LiTT procedure efficacy whilst improving the safety and should thus be investigated further.

Molecular insights into the development of hepatic metastases in colorectal cancer: a metastasis prediction study.

OBJECTIVE: Colorectal cancer is presently the third most commonly diagnosed cancer in the United States. In this study, we identified molecular differences between hepatic and non-hepatic metastases in colorectal cancer and evaluated their prognostic significance. MATERIALS AND METHODS: We downloaded primary data from the NCBI Gene Expression Omnibus (GSE6988, GSE62321, GSE50760, and GSE28722). To identify the molecular differences, we used the Significance Analysis of Microarray method. We selected nine prognostic genes (SYTL2, PTPLAD1, CDS1, RNF138, PIGR, WDR78, MYO7B, TSPAN3, and ATP5F1) with hepatic metastasis prediction score in colorectal cancer (hereafter referred to as LASSO Score). We confirmed the prognostic significance of the LASSO Score by using Kaplan-Meier survival analysis, multivariate analysis, the time-dependent area under the curve (AUC) of Uno's C-index, and the AUC of the receiver operating characteristic curve at 1-5 years. RESULTS: Survival analysis revealed that a high LASSO Score is associated with a poor prognosis in colorectal cancer patients with hepatic metastases (p = 0). Analysis of C-indices and AUC values from the receiver operating characteristic curve further supported this prediction by the LASSO Score. Multivariate analysis confirmed the prognostic significance of the LASSO Score (p = 1.13e-06). CONCLUSIONS: This study reveals the biological mechanisms underlying hepatic metastases in colorectal cancer and will help in developing targeted therapies for colorectal cancer.

Reducing AB plasma utilisation through the AB plasma appropriateness index.

OBJECTIVES: We hypothesised that there was inappropriate group AB plasma used in our hospital, identifiable by a novel key quality indicator (KQI) and mitigable through massive transfusion protocol (MTP) modification. BACKGROUND: Group AB plasma is a scarce resource strained by increasing usage worldwide when used as universal donor plasma in non-group AB patients. To reduce inappropriate use and to promote benchmarking to the best practice, we developed the AB plasma appropriateness index (ABAI). ABAI is the ratio of AB plasma transfused to group AB or unknown blood group patients to all AB plasma utilised, where values closer to 1 are better. METHODS: Data collected included AB plasma disposition by blood group, indications for transfusion, total blood utilisation, patient clinical characteristics and outcomes. ABAI during a 12-month period was retrospectively assessed, which led to implementation of pre-thawed group A plasma instead of group AB plasma for trauma patients starting in July 2017. RESULTS: The ABAI retrospectively showed inappropriate use in non-group AB patients in our hospital, the majority used to avoid expiry after thaw. When comparing 1-year pre- and post-implementation periods, ABAI improved from 0·464 to 0·900 (P < 0·0001). After exclusion of therapeutic plasma exchange, ABAI still improved (0·486-0·720, P < 0·0001). No differences in the length of stay or mortality associated in 32 patients receiving group A plasma for emergency release were observed. CONCLUSION: The ABAI is a novel KQI to indicate inappropriate AB plasma usage for quality improvement. This led to thawed A plasma use for MTPs, reducing inappropriate AB plasma usage.

Ultrafast x-ray absorption near edge spectroscopy of Fe3O4 using a laboratory based femtosecond x-ray source.

Ultrafast time-resolved x-ray absorption near edge spectroscopy (XANES) experiment was performed on a magnetite (Fe3O4) film using a femtosecond laser plasma x-ray source delivering Bremsstrahlung radiation. Ultrafast temporal evolution of the XANES of Fe3O4 following an excitation by an infra-red (IR) laser pulse was observed in a pump-probe scheme. The Fe K x-ray absorption edge shifts towards low energy upon IR excitation as much as 12 eV, which is mainly attributed to the charge transfer between the Fe ions. The shift in the absorption edge occurred within about 150 fs, typical time of non-thermal electronic redistribution. The charge transfer also causes an ultrafast increase in the IR transmission in the similar time scale.

Novel GP64 envelope variants for improved delivery to human airway epithelial cells.

Lentiviral vectors pseudotyped with the baculovirus envelope protein GP64 transduce primary cultures of human airway epithelia (HAE) at their apical surface. Our goal in this study was to harness a directed evolution approach to develop a novel envelope glycoprotein with increased transduction properties for HAE. Using error-prone PCR, a library of GP64 mutants was generated and used to prepare a diverse pool of lentiviral virions pseudotyped with GP64 variants. The library was serially passaged on HAE and three GP64 mutations were recovered. Single-, double- and the triple-combination mutant envelope glycoproteins were compared with wild-type GP64 for their ability to transduce HAE. Our results suggest that lentiviral vectors pseudotyped with evolved GP64 transduced HAE with greater efficiency than wild-type GP64. This effect was not observed in primary cultures of porcine airway epithelial cells, suggesting that the directed evolution protocol was species specific. In summary, our studies indicate that serial passage of a GP64 mutant library yielded specific variants with improved HAE cell tropism, yielding tools with the potential to improve the success of gene therapy for airway diseases.

Outcomes of sympathectomy and vascular bypass for digital ischaemia in connective tissue disorders.

All patients (36 hands) with connective tissue disorders who underwent periarterial sympathectomy of the hand alone or in conjunction with vascular bypass at our institution between 1995-2013 were reviewed. The durable resolution of ulcers was significantly higher in patients treated by periarterial sympathectomy and bypass than in patients treated by periarterial sympathectomy alone. Although there were more digital amputations in patients treated by periarterial sympathectomy alone, the difference was not statistically significant. Vascular bypass in conjunction with sympathectomy may be better than sympathectomy alone in patients with digital ischaemia related to connective tissue disorders. LEVEL OF EVIDENCE: IV.

Lower urinary cotinine level is associated with a trend toward more myopic refractive errors in Korean adolescents.

PurposeTo investigate the association between urinary cotinine levels as an objective biological marker for exposure to nicotine and refractive status.Patients and methodsThis cross-sectional study analyzed data from the Korea National Health and Nutrition Examination Survey between 2008 and 2011. A total of 1139 Korean adolescents aged 12-18 years were enrolled. Urinary cotinine concentrations and other potential risk factors for myopia were examined. Correlation analyses and multivariate regression analysis were performed to investigate the association between urinary cotinine level and refractive error.ResultsSpherical equivalent correlated significantly with urinary cotinine concentration (r=0.104, P=0.011). Lower urinary cotinine level was associated with a trend toward more myopic refractive errors (P for trend=0.003). After adjusting for age, sex, area of residence, physical activity, serum 25-hydroxyvitamin D level, parental income level, and receipt of basic livelihood security, subjects with a low urinary cotinine level had a significantly increased risk of myopia <-0.5 D (odds ratio (OR) 1.95, 95% confidence interval (CI) 1.18-3.21), <-3.0 D (OR 2.03, 95% CI 1.29-3.2), and <-6.0 D (OR 2.2, 95% CI, 1.15-4.23) when compared with subjects with a high urinary cotinine level. As urinary cotinine level decreased, the risks of myopia <-0.5 D, <-3.0 D, and <-6.0 D increased significantly (P for trend <0.05).ConclusionA trend toward less myopic refractive error was observed among Korean adolescents with higher urinary cotinine levels. This result provides the epidemiologic evidence implying nicotine as a potential modulator related with refractive development. Further studies with full consideration for myopia-associated risk factors are required to yield clear answers on the direct effect of smoking to the refractive status.

Spontaneous and indicated preterm delivery risk is increased among overweight and obese women without prepregnancy chronic disease.

OBJECTIVE: To investigate the independent impact of prepregnancy obesity on preterm delivery among women without chronic diseases by gestational age, preterm category and parity. DESIGN: A retrospective cohort study. SETTING: Data from the Consortium on Safe Labor (CSL) in the USA (2002-08). POPULATION: Singleton deliveries at ≥23 weeks of gestation in the CSL (43 200 nulliparas and 63 129 multiparas) with a prepregnancy body mass index (BMI) ≥18.5 kg/m2 and without chronic diseases. METHODS: Association of prepregnancy BMI and the risk of preterm delivery was examined using Poisson regression with normal weight as reference. MAIN OUTCOME MEASURES: Preterm deliveries were categorised by gestational age (extremely, very, moderate to late) and category (spontaneous, indicated, no recorded indication). RESULTS: Relative risk of spontaneous preterm delivery was increased for extremely preterm among obese nulliparas (1.26, 95% CI: 0.94-1.70 for overweight; 1.88, 95% CI: 1.30-2.71 for obese class I; 1.99, 95% CI: 1.32-3.01 for obese class II/III) and decreased for moderate to late preterm delivery among overweight and obese multiparas (0.90, 95% CI: 0.83-0.97 for overweight; 0.87, 95% CI: 0.78-0.97 for obese class I; 0.79, 95% CI: 0.69-0.90 for obese class II/III). Indicated preterm delivery risk was increased with prepregnancy BMI in a dose-response manner for extremely preterm and moderate to late preterm among nulliparas, as it was for moderate to late preterm delivery among multiparas. CONCLUSIONS: Prepregnancy BMI was associated with increased risk of preterm delivery even in the absence of chronic diseases, but the association was heterogeneous by preterm categories, gestational age and parity. TWEETABLE ABSTRACT: Obese nulliparas without chronic disease had higher risk for spontaneous delivery <28 weeks of gestation.

Increased risk of attention-deficit/hyperactivity disorder associated with exposure to organophosphate pesticide in Taiwanese children.

Attention-deficit/hyperactivity disorder (ADHD) is male predominated, and the etiology of this disorder remains unclear. Past studies have assessed the association of low-level organophosphate pesticide exposure with childhood ADHD cross-sectionally and prospectively. However, the results have been inconsistent. A first case-control study was performed to investigate the relationship between organophosphate pesticide exposure and ADHD with adjusted covariates. We recruited 97 doctor-diagnosed ADHD cases and 110 non-ADHD controls who were 4-15 years of age. Exposure was assessed using urinary levels of dialkylphosphate metabolites, which are biomarkers of OP pesticide exposure. Blood lead levels and polymorphisms of two commonly verified dopaminergic-related genes (the D4 dopamine receptor gene DRD4 and the dopamine transporter gene DAT1) were also analyzed. The sociodemographics and lifestyles of the children and of the mothers during pregnancy were collected using a questionnaire. The blood lead levels of both groups were similar (1.57 ± 0.73 vs. 1.73 ± 0.77 µg/dL, p = 0.15). Significant urinary concentration differences in one of the six dialkylphosphate metabolites, dimethylphosphate (DMP), were found between ADHD and control subjects (322.92 ± 315.68 vs. 224.37 ± 156.58 nmol/g cr., p < 0.01). A dose-response relationship was found between urinary concentrations of DMP and ADHD in both crude and adjusted analyses (p for trend<0.05). Children with higher urinary DMP concentrations may have a twofold to threefold increased risk of being diagnosed with ADHD. We report a dose-response relationship between child DMP levels and ADHD. Organophosphate pesticide exposure may have deleterious effects on children's neurodevelopment, particularly the development of ADHD.

The effects of prophylactic bolus phenylephrine on hypotension during low-dose spinal anesthesia for cesarean section.

BACKGROUND: Continuously infused phenylephrine is frequently used to reduce the incidence of hypotension in women undergoing cesarean section under spinal anesthesia, but less is known about the prophylactic bolus method. We evaluated three prophylactic bolus doses of phenylephrine during low-dose spinal anesthesia for cesarean section. METHODS: One-hundred-and-eighty-four patients were randomized to receive 0.9% saline 2mL (Control Group) or phenylephrine 1.0µg/kg (PHE1 Group), 1.5µg/kg (PHE1.5 Group), or 2.0µg/kg (PHE2 Group) immediately after induction of combined spinal-epidural anesthesia. Maternal blood pressure and heart rate were recorded at 1-min intervals until delivery. Hypotension, defined as systolic blood pressure <80% of baseline, was treated with rescue doses of phenylephrine 100µg at 1-min intervals until hypotension resolved. The incidence of nausea, vomiting, bradycardia, and hypertension, as well as Apgar scores and umbilical blood gases, were recorded. RESULTS: The incidence of hypotension was 71.7% (33/46) in the Control Group, 68.9% (31/45) in the PHE1 Group, 37.0% (17/46) in the PHE1.5 Group and 45.7% (21/46) in the PHE2 Group (P=0.001). The total rescue dose of phenylephrine was greater in the Control Group than those in the PHE1.5 Group (P<0.05) and PHE2 Group (P<0.05). The incidence of hypertension increased as the dose of prophylactic phenylephrine increased (P<0.001) and was highest in the PHE2 group (37%). Other variables did not differ among the four groups. CONCLUSIONS: Under the conditions of this study, prophylactic bolus injection of phenylephrine 1.5µg/kg was a suitable alternative method for reducing the incidence of hypotension during low-dose spinal anesthesia for cesarean section.

GSTP1 is a hub gene for gene-air pollution interactions on childhood asthma.

There is growing evidence that multiple genes and air pollutants are associated with asthma. By identifying the effect of air pollution on the general population, the effects of air pollution on childhood asthma can be better understood. We conducted the Taiwan Children Health Study (TCHS) to investigate the influence of gene-air pollution interactions on childhood asthma. Complete monitoring data for the ambient air pollutants were collected from Taiwan Environmental Protection Agency air monitoring stations. Our results show a significant two-way gene-air pollution interaction between glutathione S-transferase P (GSTP1) and PM10 on the risk of childhood asthma. Interactions between GSTP1 and different types of air pollutants have a higher information gain than other gene-air pollutant combinations. Our study suggests that interaction between GSTP1 and PM10 is the most influential gene-air pollution interaction model on childhood asthma. The different types of air pollution combined with the GSTP1 gene may alter the susceptibility to childhood asthma. It implies that GSTP1 is an important hub gene in the anti-oxidative pathway that buffers the harmful effects of air pollution.

Engineering a serum-resistant and thermostable vesicular stomatitis virus G glycoprotein for pseudotyping retroviral and lentiviral vectors.

Vesicular stomatitis virus G glycoprotein (VSV-G) is the most widely used envelope protein for retroviral and lentiviral vector pseudotyping; however, serum inactivation of VSV-G pseudotyped vectors is a significant challenge for in vivo gene delivery. To address this problem, we conducted directed evolution of VSV-G to increase its resistance to human serum neutralization. After six selection cycles, numerous common mutations were present. On the basis of their location within VSV-G, we analyzed whether substitutions in several surface exposed residues could endow viral vectors with higher resistance to serum. S162T, T230N and T368A mutations enhanced serum resistance, and additionally K66T, T368A and E380K substitutions increased the thermostability of VSV-G pseudotyped retroviral vectors, an advantageous byproduct of the selection strategy. Analysis of a number of combined mutants revealed that VSV-G harboring T230N+T368A or K66T+S162T+T230N+T368A mutations exhibited both higher in vitro resistance to human serum and higher thermostability, as well as enhanced resistance to rabbit and mouse serum. Finally, lentiviral vectors pseudotyped with these variants were more resistant to human serum in a murine model. These serum-resistant and thermostable VSV-G variants may aid the application of retroviral and lentiviral vectors to gene therapy.

Pancreatic adenocarcinoma upregulated factor, a novel endothelial activator, promotes angiogenesis and vascular permeability.

Pancreatic adenocarcinoma upregulated factor (PAUF) was recently reported to be a metastasis factor for pancreatic cancer cells. Here, we demonstrate a novel role for PAUF as a potent endothelial activator, promoting both angiogenesis and vascular permeability. Overexpression of PAUF in a mouse pancreatic cancer model resulted in increased tumor vascularity. Recombinant PAUF (rPAUF) enhanced proliferation, migration and capillary-like tube formation of human endothelial cells (ECs), consistently with increased neovascularization in vivo. rPAUF also increased endothelial permeability through the disruption of vascular endothelial-cadherin-facilitated cell-cell junctions in vitro and induced vascular leakage in mouse skin. These effects were attenuated upon treatment with an antibody against PAUF. Moreover, PAUF evoked a time- and dose-dependent activation of extracellular signal-regulated kinase (ERK)1/2, AKT and endothelial NO synthase (eNOS) in ECs, which are closely linked to rPAUF-induced angiogenesis. Finally, rPAUF upregulated the expression of C-X-C chemokine receptor 4 (CXCR4) in ECs and potentiated the in vitro and in vivo EC angiogenic responses to stromal cell-derived factor-1 (SDF-1), a ligand for CXCR4. Taken together, these data demonstrate that PAUF has a novel function in promoting angiogenesis and vascular permeability. Our findings suggest new possibilities for PAUF's role in the pathogenesis of angiogenesis-dependent diseases.

Fungal peri-prosthetic joint infection after primary total knee replacement.

We retrospectively reviewed 30 two-stage revision procedures in 28 patients performed for fungal peri-prosthetic joint infection (PJI) after a primary total knee replacement. Patients were followed for at least two years or until the infection recurred. The mean follow-up for patients who remained free of infection was 4.3 years (2.3 to 6.1). Overall, 17 patients were assessed as American Society of Anesthesiologists grade 3 or 4. The surgical protocol included removal of the infected implant, vigorous debridement and insertion of an articulating cement spacer. This was followed by at least six weeks of antimicrobial treatment and delayed reimplantation in all patients. The mean interval between removal of the prosthesis and reimplantation was 9.5 weeks (6 to 24). After reimplantation, patients took antifungal agents orally for a maximum of six months. Two knees became reinfected at one and two months post-operatively, respectively: one of these subsequently required arthrodesis because of uncontrolled infection. Fungal PJIs can be treated successfully by removal of all infected material, appropriate antimicrobial treatment and delayed reimplantation.

Prognostic factors for recurrence after bilateral rectus recession procedure in patients with intermittent exotropia.

PURPOSE: The purpose of this study is to evaluate prognostic factors, specifically age, at the time of surgery, for recurrence after bilateral lateral rectus recession (BLR) in patients with intermittent exotropia. METHODS: Medical records of 511 subjects who underwent BLR procedures between the ages of 3 and 10 years with more than 12 months of follow-up were retrospectively reviewed. Patients' surgical outcomes with a deviation of less than 10 prism diopters (PD) exotropia and less than 5 PD esotropia were defined as a success. Outcomes with more than 11 PD exotropia were designated as recurrences, and those with esotropia of more than 5 PD after 3 months of surgery were noted as overcorrection. Prognostic factors for recurrence were analyzed by multivariate logistic regression test. RESULTS: Of the 511 subjects, 371 had successful surgical outcomes and 129 had recurrences, whereas 11 were found to be overcorrected. Age at surgery and immediate postoperative alignment proved to be significant factors influencing a favorable outcome by multivariate logistic regression analysis (P<0.05). However, gender, photophobia, age at onset, spherical equivalent (SE) refractive error, astigmatism, SE anisometropia, and preoperative deviation size were not significantly predictive of success (P>0.05). CONCLUSION: In BLR procedures, increasing patient age at surgery was associated with lower recurrence rates.

The P2-Na(2/3)Co(2/3)Mn(1/3)O2 phase: structure, physical properties and electrochemical behavior as positive electrode in sodium battery.

Manganese substituted sodium cobaltate, Na(2/3)Co(2/3)Mn(1/3)O(2), with a layered hexagonal structure (P2-type) was obtained by a co-precipitation method followed by a heat treatment at 950 °C. Powder X-ray diffraction analysis revealed that the phase is pure in the absence of long-range ordering of Co and Mn ions in the slab or Na(+) and vacancy in the interslab space. The oxidation states of the transition metal ions were studied by magnetic susceptibility measurements, electron paramagnetic resonance (ESR) and (23)Na magic angle spinning nuclear magnetic resonance (MAS NMR) spectroscopy. The charge compensation is achieved by the stabilization of low-spin Co(3+) and Mn(4+) ions. The capability of Na(2/3)Co(2/3)Mn(1/3)O(2) to intercalate and deintercalate Na(+) reversibly was tested in electrochemical sodium cells. It appears that the P2 structure is maintained during cycling, the cell parameter evolution versus the sodium amount is given. From the features of the cycling curve the formation of an ordered phase for the Na(0.5)Co(2/3)Mn(1/3)O(2) composition is expected.

Molds, parental atopy and pediatric incident asthma.

UNLABELLED: To assess the independent and joint effects of parental atopy and exposure to molds on the development of asthma in childhood, the authors conducted a cohort-based, incident case-control study in 2008. The case group consisted of 188 children with new asthma, and the control group (n=376) was matched one to two for age and sex. The outcome of interest was the development of asthma during the study period. The studied determinants were parental atopy and three indicators of exposure including histories of water damage, presence of visible molds, and perceived mold odor in the home at baseline in 2002. In conditional logistic regression adjusting for confounding, parental atopy [adjusted odds ratio (aOR) 3.29, 95% CI 2.19-4.94] and the presence of mold odor (aOR 2.09, 95% CI 1.30-3.37) and visible mold (aOR 1.76, 95% CI 1.18-2.62) were independent determinants of incident asthma, and apparent interaction in additive scale was observed. Our finding suggests that the interaction between parental atopy and molds may play a role in the development of asthma in children. PRACTICAL IMPLICATIONS: Our study strengthens the evidence for the roles of indoor dampness problem and parental atopy as determinants of asthma in children. Furthermore, the interaction between parental atopy and exposure to molds suggests a role for the development of childhood asthma, i.e., the children whose parents had atopic disease and molds exposure are more susceptible to develop asthma.