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Asthma remains one of the most important challenges to pediatric public health in the US. A large majority of children with persistent and chronic asthma demonstrate aeroallergen sensitization, which remains a pivotal risk factor associated with the development of persistent, progressive asthma throughout life. In individuals with a tendency toward Type 2 inflammation, sensitization and exposure to high concentrations of offending allergens is associated with increased risk for development of, and impairment from, asthma. The cascade of biological responses to allergens is primarily mediated through IgE antibodies and their production is further stimulated by IgE responses to antigen exposure. In addition, circulating IgE impairs innate anti-viral immune responses. The latter effect could magnify the effects of another early life exposure associated with increased risk of the development of asthma - viral infections. Omalizumab binds to circulating IgE and thus ablates antigen signaling through IgE-related mechanisms. Further, it has been shown restore IFN-α response to rhinovirus and to reduce asthma exacerbations during the viral season. We therefore hypothesized that early blockade of IgE and IgE mediated responses with omalizumab would prevent the development and reduce the severity of asthma in those at high risk for developing asthma. Herein, we describe a double-blind, placebo-controlled trial of omalizumab in 2-3 year old children at high risk for development of asthma to prevent the development and reduce the severity of asthma. We describe the rationale, methods, and lessons learned in implementing this potentially transformative trial aimed at prevention of asthma., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Effects of environmental microbial exposures on human health have long been of interest. Microbes were historically assumed to be harmful, but data have suggested that microbial exposures can modulate the immune system. We focus on the effects of indoor environmental microbial exposure on chronic lung diseases. We found contradictory data in bacterial studies using endotoxin as a surrogate for bacterial exposure. Contradictory data also exist in studies of fungal exposure. Many factors may modulate the effect of environmental microbial exposures on lung health, including coexposures. Future studies need to clarify which method of assessing environmental microbial exposures is most relevant., Competing Interests: Disclosure ▪, (Copyright © 2020 Elsevier Inc. All rights reserved.)

Hyoid bone fractures due to blunt trauma are rare accounting for only 0.002% of all head and neck fractures with most documented fractures being due to strangulation, hanging, motorcycle helmet straps, sports injuries and rarely as a complication of intubation. However, they are even rarer in the paediatric age group. We present a hyoid bone fracture in a two-year-old child as a result of a fall down three steps. Hyoid bone fractures though generally heal well with conservative treatment must be diagnosed early to avoid air way obstruction leading to morbidity and mortality., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Much research has demonstrated the beneficial effects of mindfulness-based stress reduction (MBSR) on psychological and physical health, but it is not known whether MBSR may impact cellular aging in healthy populations. Further, little research has evaluated MBSR against an active control condition, which precludes strong conclusions regarding the unique effects of mindfulness on psychological functioning. The present study examined the effects of MBSR versus music therapy-based stress reduction (MTSR) on trait mindfulness, self-compassion, and several psychological health outcomes, as well as leukocyte telomere length (LTL). One hundred and fifty eight Singaporean Chinese adults were recruited and randomly assigned to an eight-week MBSR or MTSR course. Participants provided blood samples and completed a battery of self-report measures pre- and post-intervention. Analyses showed that participants in the MBSR condition demonstrated significantly greater improvements in depressive symptoms, trait mindfulness, and self-compassion compared to the control condition. Treatment condition did not predict changes in LTL, anxiety, stress, or happiness, though there was a trend for duration of home mindfulness practice to predict increases in LTL. Overall, the study demonstrated MBSR's unique effects in reducing depressive symptoms. Improvements in trait mindfulness and self-compassion correspond with theorized mechanisms of change underlying mindfulness training. The lack of intervention effect with regards to LTL suggests that a more intensive intervention may be required for mindfulness to exert noticeable impact on aging at the cellular level, or that the effect may only emerge over a longer term., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Sparse data address the effects of nitrogen dioxide (NO 2 ) exposure in inner-city schools on obese students with asthma., Objective: We sought to evaluate relationships between classroom NO 2 exposure and asthma symptoms and morbidity by body mass index (BMI) category., Methods: The School Inner-City Asthma Study enrolled students aged 4 to 13 years with asthma from 37 inner-city schools. Students had baseline determination of BMI percentile. Asthma symptoms, morbidity, pulmonary inflammation, and lung function were monitored throughout the subsequent academic year. Classroom NO 2 data, linked to enrolled students, were collected twice per year. We determined the relationship between classroom NO 2 levels and asthma outcomes by BMI stratification., Results: A total of 271 predominantly black (35%) or Hispanic students (35%) were included in analyses. Fifty percent were normal weight (5-84th BMI percentile), 15% overweight (≥85-94th BMI percentile), and 35% obese (≥95th BMI percentile). For each 10-parts per billion increase in NO 2 , obese students had a significant increase in the odds of having an asthma symptom day (odds ratio [OR], 1.86; 95% CI, 1.15-3.02) and in days caregiver changed plans (OR, 4.24; 95% CI, 2.33-7.70), which was significantly different than normal weight students who exhibited no relationship between NO 2 exposure and symptom days (OR, 0.90; 95% CI, 0.57-1.42; pairwise interaction P = .03) and change in caregiver plans (OR, 1.37; 95% CI, 0.67-2.82; pairwise interaction P = .02). Relationships between NO 2 levels and lung function and fractional exhaled nitric oxide did not differ by BMI category. If we applied a conservative Holm-Bonferroni correction for 16 comparisons (obese vs normal weight and overweight vs normal weight for 8 outcomes), these findings would not meet statistical significance (all P > .003)., Conclusions: Obese BMI status appears to increase susceptibility to classroom NO 2 exposure effects on asthma symptoms in inner-city children. Environmental interventions targeting indoor school NO 2 levels may improve asthma health for obese children. Although our findings would not remain statistically significant after adjustment for multiple comparisons, the large effect sizes warrant future study of the interaction of obesity and pollution in pediatric asthma., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Congenital hemidysplasia with ichthyosiform erythroderma and limb defects also known as CHILD syndrome is an X-linked dominant, male lethal genodermatosis with a prevalence of 1 in 100,000 live births. Mutations in NSDHL gene located at Xq28 potentially impair the function of NAD(P) H steroid dehydrogenase-like protein and is responsible for its pathogenesis., Case Presentation: The proband was a 9-month-old twin (T2) girl with a healthy twin sister (T1) of Sri Lankan origin born to non-consanguineous parents. She presented with right sided continuous icthyosiform erythroderma and ipsilateral limb defects and congenital hemidysplasia since birth. Notably the child had ipsilateral hand hypoplasia and syndactyly. There were other visceral abnormalities. We performed whole exome sequencing and found a novel heterozygous variant (NSDHL, c.713C > A, p.Thr238Asn)., Conclusion: We report a novel missense variant in the NSDHL gene that resides in a highly-conserved region. This variant affects the NAD(P) H steroid dehydrogenase-like protein function via reduction in the number of active sites resulting in the CHILD syndrome phenotype and syndactyly.

Point mutations are a common form of genetic variation and have been identified as important disease biomarkers. Conventional methods for analyzing point mutations, e.g., polymerase chain reaction (PCR), are based on differences in thermal stability of the DNA duplex, which require extensive optimization of the reaction condition and nontrivial design of sequence-selective primers. This motivated the design of molecular translators to convert molecular inputs into generic output sequences, which allows for the target recognition and signal generation regions to be designed independently. In this work, we propose a translator design based on the concept of split proximity circuit (SPC) to achieve both high sequence selectivity and assay robustness using a universal reaction condition, i.e., room temperature and constant ionic concentration. We discussed the design aspects of the SPC recognition regions and demonstrated its plug-and-play capability to discriminate different point mutations for both DNA (seven G6PD mutations) and RNA (let-7 microRNA family members) targets while retaining the same signal generation region. Despite its simple design and nonstringent assay condition requirements, the SPC retained good analytical performance to detect subnanomolar target concentration within a reasonable time of an hour.

Graphene oxide (GO) has the ability to absorb certain compounds, and it can be modified with functional groups for different purposes; for instance, iron oxide (IO) nanoparticles can be used to concentrate analyte by a magnet. Recently, many kinds of GO have been developed, such as single-layer GO (SLGO), two-to-four layers of GO (i.e., few-layer GO, FLGO 2-4 ), and four-to-eight layers of GO (i.e., multi-layer GO, MLGO 4-8 ). However, the abilities of these layered GO coated with IO nanoparticles have not been investigated. In this study, we conducted a novel analysis of glimepiride by using layered GO-coated magnetic clusters of IO nanoparticles that were synthesized through a simple and facile emulsion-solvent evaporation method. The methodology is based on (i) enrichment of glimepiride using the layered GO-coated magnetic clusters of IO nanoparticles (IO@SLGO, IO@FLGO 2-4 , and IO@MLGO 4-8 ), and (ii) rapid determination using magnetic cluster-based surface-assisted laser desorption/ionization time-of-flight mass spectrometry (SALDI-TOFMS). We found that IO@MLGO 4-8 , the magnetic cluster with the greatest number of GO layers, had the best limit of detection (28.6 pmol/μL for glimepiride). The number of GO layers played a significant role in increasing the sensitivity of the SALDI-MS, indicating that the size of GO in the magnetic clusters contributed to the desorption/ionization efficiency. To the best of our knowledge, this is the first study to enrich glimepiride using magnetic clusters of different GO types and to show that the glimepiride in HLB purified urine adsorbed by magnetic clusters can be analyzed by SALDI-TOFMS.

An amendment to this paper has been published and can be accessed via the original article.

Background: Antibiotic use for livestock is presumed to be a contributor to the acquisition of antimicrobial resistance (AMR) genes in humans, yet studies do not capture AMR data before and after livestock introduction., Methods: We performed a feasibility study by recruiting a subset of women in a delayed-start randomized controlled trial of small-scale chicken farming to examine the prevalence of clinically-relevant AMR genes. Stool samples were obtained at baseline and one year post-randomization from five intervention women who received chickens at the start of the study, six control women who did not receive chickens until the end of the study, and from chickens provided to the control group at the end of the study. Stool was screened for 87 clinically significant AMR genes using a commercially available qPCR array (Qiagen)., Results: Chickens harbored 23 AMR genes from classes found in humans as well as additional vancomycin and β-lactamase resistance genes. AMR patterns between intervention and control women appeared more similar at baseline than one year post randomization (PERMANOVA R2 = 0.081, p = 0.61 at baseline, R2 = 0.186, p = 0.09 at 12 months) Women in the control group who had direct contact with the chickens sampled in the study had greater similarities in AMR gene patterns to chickens than those in the intervention group who did not have direct contact with chickens sampled (p = 0.01). However, at one year there was a trend towards increased similarity in AMR patterns between humans in both groups and the chickens sampled (p = 0.06)., Conclusions: Studies designed to evaluate human AMR genes in the setting of animal exposure should account for high baseline AMR rates. Concomitant collection of animal, human, and environmental samples over time is recommended to determine the directionality and source of AMR genes., Trial Registration: ClinicalTrials.gov Identifier NCT02619227., Competing Interests: The authors have declared that no competing interests exist.

Both the host microbiome and the microbiome of the built environment can have profound impacts on human health. While prior studies have suggested that the variability introduced by DNA extraction method is less than typical biologic variation, most studies have focused on 16S rRNA amplicon sequencing or on high biomass fecal samples. Shotgun metagenomic sequencing provides advantages over amplicon sequencing for surveying the microbiome, but is a challenge to perform in lower microbial biomass samples with high human DNA content such as sputum or vacuumed dust. Here we systematically evaluate the impact of four different extraction methods (phenol:choloroform, and three high-throughput kit-based approaches, the Promega Maxwell gDNA, Qiagen MagAttract PowerSoil DNA, and ZymoBIOMICS 96 MagBead). We report the variation in microbial community structure and predicted microbial function assessed by shotgun metagenomics sequencing in human stool, sputum, and vacuumed dust obtained from ongoing cohort studies or clinical trials. The same beadbeating protocol was used for all samples to focus our evaluation on the impact of kit chemistries on sequencing results. DNA yield was overall highest in the phenol:choloroform and Promega approaches. Only the phenol:choloroform approach showed evidence of contamination in negative controls. Bias was evaluated using mock community controls, and was noted across all extraction methods, although Promega exhibited the least amount of bias. The extraction method did not impact the proportion of human reads, although stool had the lowest proportion of human reads (0.1%) as compared to dust (44.1%) and sputum (80%). We calculated Bray-Curtis dissimilarity and Aitchison distances to evaluate the impact of extraction method on microbial community structure by sample type. Extraction method had the lowest impact in stool (extraction method responsible for 3.0-3.9% of the variability), the most impact in vacuumed dust (12-16% of the variability) and intermediate values for sputum (9.2-12% variability). Similar differences were noted when evaluating microbial community function. Our results will inform investigators planning microbiome studies using diverse sample types in large clinical studies. A consistent DNA extraction approach across all sample types is recommended, particularly with lower microbial biomass samples that are more heavily influenced by extraction method., (Copyright © 2020 Sui, Weil, Nuwagira, Qadri, Ryan, Mezzari, Phipatanakul and Lai.)

Introduction: Methanol is a widely available chemical with a range of uses including as solvent, as a fuel, in chemical synthesis and anti-freeze preparations. Most of the cases are accidental exposures to drinking beverages contaminated with methanol., Materials and Methods: In mid-September 2018, there was a single outbreak of methanol poisoning in Malaysia especially involving the state of Federal Territory Kuala Lumpur and Selangor. There were 33 reported deaths suspected due to methanol poisoning in this current outbreak where 11 of them were brought in to the Institute of Forensic Medicine (NIFM), Kuala Lumpur. The last outbreak was in the year 2013 with 29 deaths reported out of 44 cases., Results: There were 3 cases (27.2%) died in hospital and the remaining 8 cases (72.8%) were found dead at home and were later brought in dead to the hospital. A full autopsy was carried out for each case. Autopsy findings, as well as lab results pertaining to cases that survived and directly brought in dead, were of a different spectrum., Conclusion: Methanol related deaths are almost always as a result of greed. The running truism is 'methanol poisoning is a result of deliberate addition/adulteration with industrial methanol'. Prevention of the illegal production of methanol and methylated spirits should be established to curb this matter in the future.

Background: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration or loss of lower motor neurons. The survival of motor neuron (SMN) 1 gene, which produces the SMN protein, has been identified as a responsible gene for the disease. SMN is ubiquitously expressed in any tissue and may play an important role on the metabolism in the human body. However, no appropriate biomarkers reflecting the alteration in the metabolism in SMA have been identified., Methods: Low-molecular-weight metabolites were extracted from plasma of 20 human infants (9 SMA type 1 patients and 11 controls) and 9 infant mice (5 SMA-model mice, 4 control mice), and derivatized with N-methyl-N-trimethylsilyltrifluoroacetamide. Finally, the derivatized products were applied to Gas Chromatography/Mass Spectrometry apparatus. To confirm the metabolite abnormality in SMA type 1 patients, we performed SMN-silencing experiment using a hepatocyte-derived cell line (HepG2)., Results: We performed a comprehensive metabolomics analysis of plasma from the patients with SMA type 1 and controls, and found that phosphoethanolamine (PEA) was significantly higher in the patients than in the controls. HepG2 experiment also showed that SMN-silencing increased PEA levels. However, comprehensive metabolomics analysis of plasma from SMA-model mice and control mice showed different profile compared to human plasma; there was no increase of PEA even in the SMA-model mice plasma., Conclusion: Our data suggested that PEA was one of the possible biomarkers of human SMA reflecting metabolic abnormalities due to the SMN protein deficiency.

CKD-associated pruritus is one of the common symptoms in patients undergoing dialysis, thus contributing to the diminished and compromised quality of life. This study aimed to explore the association between the CKD-associated pruritus on quality of life of patients undergoing hemodialysis in Malaysia. A cross-sectional multicenter study, carried out from February to September 2017 at tertiary care settings in Kuala Lumpur, Malaysia. Patients aged 18 years and above, undergoing hemodialysis, understanding Malay language and willing to participate were included. The CKD-associated pruritus was assessed by using Malay 5D-itch scale and Malay FANLTC questionaiare. To determine the factors associated with pruritus and quality of life, multivariate logistic regression analysis was used having P value < 0.05 as statistically significant. Among n = 334 recruited patients with a response rate of 100%, 59.6% were males and total of 61.3% were having CKD-associated pruritus. The results showed a statistically significant weak negative correlation between CKD-associated pruritus and quality of life. Multivariate linear regression revealed none of these factors were found to be associated with pruritus; however, CKD-associated prurtius was found to be associated with quality of life score. CKD-associated pruritus is have a negative impact on the patient's quality of life including physical, social, mental/emotional, and functional well-being. Despite the high prevalence and negative impact of CKD-associated pruritus on quality of life, it is disregarded by most health care professionals. It is thus pertinent to monitor the potential risk factors and consider providing timely treatment implications for CKD-associated pruritus in hemodialysis patients, in order to improve their quality of life., (© 2019 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Pholiota nameko , a type of edible and medicinal fungus, is currently grown extensively for food and traditional medicine in China and Japan. It possesses various biological activities, such as anti-inflammatory, anti-hyperlipidemia and antitumor activities. However, P. nameko has rarely been discussed in the field of dermatology; identifying its biological activities could be beneficial in development of a new natural ingredient used in wound care. To evaluate its in vitro wound healing activities, the present study assessed the antioxidant and anti-collagenase activities of P. nameko polysaccharides (PNPs) prepared through fractional precipitation (40%, 60% and 80% ( v / v )); the assessments were conducted using reducing power, hydroxyl radical scavenging activity, dichloro-dihydro-fluorescein diacetate and collagenase activity assays. The ability of PNPs to facilitate L929 fibroblast cell proliferation and migration was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch assays. The findings indicated that, among all fractions, PNP-80 showed the best antioxidant and anti-collagenase activity, as measured by their reducing power (IC 50 of PNP-80 was 2.43 ± 0.17 mg/mL), the hydroxyl radical scavenging (IC 50 of PNP-80 was 2.74 ± 0.11 mg/mL) and collagenase activity assay, and significantly reduced cellular ROS content, compared with that of H 2 O 2 -induced L929 cells. Moreover, PNP-80 significantly promoted L929 fibroblast proliferation and migration, compared with the control group. Overall, we suggested that PNP-80 could be a promising candidate for further evaluation of its potential application on wound healing., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Background: Despite emerging evidences on the feasibility and efficacy of single-incision laparoscopic appendectomy (SILA) for managing simple appendicitis, advancing its use for treating complicated appendicitis remains unwarranted. This study aimed to evaluate the surgical outcome of SILA compared with that of standard multiport laparoscopic appendectomy (MPLA) in the management of complicated appendicitis., Methods: Between July 2013 and September 2017, 40 patients who underwent SILA and 150 patients who underwent MPLA for the treatment of complicated appendicitis, defined as AAST grades II-V, were recruited for this study. The demographic characteristics, intraoperative and recovery parameters were retrospectively recorded. No routine drainage was placed in the SILA group., Results: SILA was smoothly performed without requiring conversion to MPLA. No significant difference was observed between the 2 groups in demography and preoperative severity. The operation duration was approximately 8 min shorter in the SILA group than in the MPLA group, without a statistical difference (60.03 ± 21.01 vs. 68.04 ± 32.03 min, p = 0.222). The recovery parameters, including soft diet intake and postoperative hospitalization, were more favorable in the SILA group (p < 0.001). Despite the absence of routine drainage in the SILA group, only 1 patient developed an intra-abdominal hematoma necessitating further computed tomography-guided drainage., Conclusion: SILA is safe and feasible for the management of complicated appendicitis. SILA had non-inferior results to MPLA in terms of time to resume oral intake and postoperative hospital stay. Furthermore, this study posted a question on the concept of routine postoperative drainage in complicated appendicitis., (Copyright © 2019. Published by Elsevier Taiwan LLC.)

Background: Traffic proximity has been associated with adverse respiratory health outcomes. Less is known about the combined impact of residential and school exposures on pediatric asthma., Objective: We sought to use spatial analysis methodology to analyze residential and school proximity to major roadways and pediatric asthma morbidity., Methods: The School Inner-City Asthma Study (n = 350) recruited school-aged children with asthma. Each participant's school and home addresses were geocoded, and distances from major roadways were measured to calculate a composite measure accounting for both home and school traffic exposure. Generalized estimating equation models were clustered by subject and adjusted for age, race/ethnicity, sex, income, environmental tobacco smoke, controller medication, upper respiratory tract infections, and seasonality., Results: The majority of participants (62%) attended schools within 100 m from major roadways, and 40% also resided within 100 m of major roadways. In multivariate analyses major roadway proximity was independently associated with increased asthma symptom days. At greater than the threshold of 100 m, children had 29% less odds of a symptom day over the past 2 weeks for each 100-m increase in distance from a major roadway (odds ratio, 0.71; 95% CI, 0.58-0.87; P < .01). Children farther from a major roadway also had significantly less reported health care use (odds ratio, 0.63; 95% CI, 0.47-0.85; P < .01) and were significantly less likely to have poor asthma control (odds ratio, 0.80; 95% CI, 0.69-0.94; P < .01). There was not a meaningful association between distance to a major roadway and lung function outcomes., Conclusions: Proximity to a major roadway, a composite measure of home and school exposure but primarily driven by home exposure, was associated with greater asthma morbidity. More studies are needed to evaluate the independent effect of school distance to a roadway on asthma morbidity., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

BACKGROUND Risk factors for venous thromboembolism can include a combination of genetic, anatomic, and physiologic factors, some of which are modifiable. Patients presenting to the hospital with venous thromboembolism may have multiple risk factors that require testing beyond the initial admission labs and hypercoagulability screening panel. CASE REPORT We describe a right-handed patient who lifts weights for exercise, who presented with pulmonary infarcts and clot in the right superior vena cava/subclavian vein. These were due to a combination of 1) an acquired hypercoagulability from minimal change disease and 2) dynamic anatomic narrowing of the subclavian vein, which is known as Paget-Schroetter syndrome. Despite normal serum levels of antithrombin, protein C and S, his serum albumin was low, which prompted workup for proteinuria. Testing revealed nephrotic range proteinuria as well as dynamic occlusion of the right subclavian vein on magnetic resonance venography only when the patient lifted and externally rotated his arms. CONCLUSIONS This case report highlights the need for a thorough history and physical examination, as well as additional testing in some patients beyond the initial admission laboratory tests and screening panel for hypercoagulability. Tests could include diagnostic imaging testing with provoking maneuvers, which can help elucidate dynamic physiology. Such testing, when appropriate, can help to inform the treatment plan and prevent recurrent thromboses.

Background: Polymerase chain reaction (PCR) analysis using DNA from dried blood spot (DBS) samples on filter paper is a critical technique for spinal muscular atrophy (SMA) newborn screening. However, DNA extraction from DBS is time-consuming, and elimination of PCR inhibitors from DBS is almost impossible., Methods: Exon 7 of the two homologous SMA-related genes, survival motor neuron (SMN) 1 and SMN2, of five SMA patients and five controls were amplified by PCR with a punched-out circle of the DBS paper. Two types of DNA preparation methods were tested; DNA-extraction (extracted DNA was added in a PCR tube) and non-DNA-extraction (a punched-out DBS circle was placed in a PCR tube). As for the DNA polymerases, two different enzymes were compared; TaKaRa Ex Taq™ and KOD FX Neo™. To test the diagnostic quality of PCR products, RFLP (Restriction fragment length polymorphism) analysis with DraI digestion was performed, differentiating SMN1 and SMN2., Results: In PCR using extracted DNA, sufficient amplification was achieved with TaKaRa Ex Taq™ and KOD FX Neo™, and there was no significant difference in amplification efficiency between them. In direct PCR with a punched-out DBS circle, sufficient amplification was achieved when KOD FX Neo™ polymerase was used, while there was no amplification with TaKaRa Ex Taq™. RFLP analysis of the direct PCR products with KOD FX Neo™ clearly separated SMN1 and SMN2 sequences and proved the presence of both of SMN1 and SMN2 in controls, and only SMN2 in SMA patients, suggesting that the direct PCR products with KOD FX Neo™ were of sufficient diagnostic quality for SMA testing., Conclusion: Direct PCR with DNA polymerases like KOD FX NeoTM has potential to be widely used in SMA newborn screening in the near future as it obviates the DNA extraction process from DBS and can precisely amplify the target sequences in spite of the presence of PCR inhibitors.

Objective: Duchenne/Becker muscular dystrophy (DMD/BMD) is the most common genetic neuromuscular disease in children, resulting from a defect in the DMD gene located on Xp21.2. The new emerging treatment using exon skipping strategy is tailored to specific mutations, thus molecular diagnostics are particularly important. This study aimed to detect the DMD gene deletion in Indonesian DMD/BMD patients and analyze the potential amenability by exon skipping therapy., Results: Thirty-four male patients were enrolled in this study, 23 of them (67.6%) underwent muscle biopsy and showed the absence or partially expressed dystrophin protein in immunohistochemistry staining. All patients had very high serum CK levels (10.529 ± 9.97 IU/L). Multiplex PCR revealed the DMD gene deletions in 15 (44.1%) cases. Seventy-eight percent of deletions were clustered in the hot-spot region of exon 43 to 52. Furthermore, seven (20.5%) patients were potentially amenable to exon skipping treatment. Therefore, multiplex PCR is one feasible method to detect DMD gene deletion in Indonesian DMD/BMD patients that can further determine the potential amenability of exon skipping therapy. In addition, this study is the first report of DMD gene deletion analysis in Indonesia.

Cancer has become a major cause of human death in many countries. Generally, chemotherapy is the main treatment for cancer, but it may kill both cancerous cells as well as normal cells that cause serious side effects in the patient due to lack of specific targeting for cancerous cells. In order to achieve better efficiency in the cancer treatment, the development of targeted drug delivery platform has been a goal for a long time. Herein, we constructed folic acid decorated azide functionalized biocompatible mesoporous silica nanoparticles (MSNPs) to target tumor cells through folate receptor (FR), a widely expressed receptor in cancer cells. In colon and ovarian cancer cells, high endogenous H 2 S levels are found. They can be used as a trigger for the azide reduction, which leads to the cleavage of ester linkage and results in DOX release from MSNP nanocarriers. Additionally, confocal cell images of HCT-116, HT-29, A2780, SKOV3, and HeLa cells treated with nanoparticles revealed an effective internalization of MSNPs in these cells. Interestingly, DOX-loaded MSNP-N 3 -FA-treated HT-29 cells showed a significant decrease in the cell viability, whereas, there was no substantial change in HeLa cells. We also demonstrated that DOX-loaded MSNP-N 3 -FA has superior in vivo chemotherapy efficacy compared to free DOX. These observations indicated that the designed nanocarriers on MSNP-N 3 -FA specifically respond in the presence of H 2 S. MSNP-N 3 -FA is the first potential nanocarrier for endogenous H 2 S-based efficient DOX release for colon and ovarian cancers.

Selection and prioritization of phenotype-centric variants remains a challenging part of variant analysis and interpretation in clinical exome sequencing. Phenotype-driven shortlisting of patient-specific gene lists can avoid missed diagnosis. Here, we analyzed the relevance of using primary Human Phenotype Ontology identifiers (HPO IDs) in prioritizing Mendelian disease genes across 30 in-house, 10 previously reported, and 10 recently published cases using three popular web-based gene prioritization tools (OMIMExplorer, VarElect & Phenolyzer). We assessed partial HPO-based gene prioritization using randomly chosen and top 10%, 30%, and 50% HPO IDs based on information content and found high variance within rank ratios across the former vs the latter. This signified that randomly selected less-specific HPO IDs for a given disease phenotype performed poorly by ranking probe gene farther away from the top rank. In contrast, the use of top 10%, 30%, and 50% HPO IDs individually could rank the probe gene among the top 1% in the ranked list of genes that was equivalent to the results when the full list of HPO IDs were used. Hence, we conclude that use of just the top 10% of HPO IDs chosen based on information content is sufficient for ranking the probe gene at top position. Our findings provide practical guidance for utilizing structured phenotype semantics and web-based gene-ranking tools to aid in identifying known as well unknown candidate gene associations in Mendelian disorders.

Background: Most of the global burden of pollution-related morbidity and mortality is believed to occur in resource-limited settings, where HIV serostatus and sex may influence the relationship between air pollution exposure and respiratory morbidity. The lack of air quality monitoring networks in these settings limits progress in measuring global disparities in pollution-related health. Personal carbon monoxide monitoring may identify sub-populations at heightened risk for air pollution-associated respiratory morbidity in regions of the world where the financial cost of air quality monitoring networks is prohibitive., Methods: From September 2015 through May 2017, we measured 48-h ambulatory carbon monoxide (CO) exposure in a longitudinal cohort of HIV-infected and uninfected adults in rural southwestern Uganda. We fit generalized mixed effects models to identify correlates of CO exposure exceeding international air quality thresholds, quantify the relationship between CO exposure and respiratory symptoms, and explore potential effect modification by sex and HIV serostatus., Results: Two hundred and sixty study participants completed 419 sampling periods. Personal CO exposure exceeded international thresholds for 50 (19%) participants. In covariate-adjusted models, living in a home where charcoal was the main cooking fuel was associated with CO exposure exceeding international thresholds (adjusted odds ratio [AOR] 11.3, 95% confidence interval [95%CI] 4.7-27.4). In sex-stratified models, higher CO exposure was associated with increased odds of respiratory symptoms among women (AOR 3.3, 95%CI 1.1-10.0) but not men (AOR 1.3, 95%CI 0.4-4.4). In HIV-stratified models, higher CO exposure was associated with increased odds of respiratory symptoms among HIV-infected (AOR 2.5, 95%CI 1.01-6.0) but not HIV-uninfected (AOR 1.4, 95%CI 0.1-14.4) participants., Conclusions: In a cohort in rural Uganda, personal CO exposure frequently exceeded international thresholds, correlated with biomass exposure, and was associated with respiratory symptoms among women and people living with HIV. Our results provide support for the use of ambulatory CO monitoring as a low-cost, feasible method to identify subgroups with heightened vulnerability to pollution-related respiratory morbidity in resource-limited settings and identify subgroups that may have increased susceptibility to pollution-associated respiratory morbidity.

Background: Whereas meditation training has been purported to support slower cellular aging, little work has explored the association among different facets of dispositional mindfulness, self-compassion, and cellular aging. The present study aimed to examine the relationship between leukocyte telomere length (LTL), an index of cellular aging, dispositional mindfulness, and self-compassion in a sample of Singaporean Chinese adults., Methods: One hundred and fifty-eight Chinese adults (mean age = 27.24 years; 63.3% female) were recruited from the community and completed self-report measures assessing dispositional mindfulness, self-compassion, and psychological symptoms, as well as provided blood samples for analyses of LTL. Multiple regression analyses were conducted to examine the role of trait mindfulness and self-compassion in predicting LTL, taking into consideration potential covariates such as chronological age and psychological symptoms., Results: Results showed that nonreactivity, one of the five facets of dispositional mindfulness, was significantly associated with LTL, after controlling for chronological age. There was also a trend for dispositional mindfulness, self-compassion, and their selected facets (i.e., nonjudging, common humanity, and de-identification) to each be associated with longer LTL., Conclusions: Overall, the findings provide preliminary support for the association among aspects of dispositional mindfulness, self-compassion, and aging. In particular, individuals high on nonreactivity experience slower aging at the cellular level, likely through engaging in more adaptive coping mechanisms.

Background: Spinal Muscular Atrophy (SMA) is a common autosomal recessive neuromuscular disease characterized by defects of lower motor neurons. More than 95% of SMA patients show homozygous deletion for the survival motor neuron 1 (SMN1) gene. For the screening of SMN1 deletion using dried blood spot (DBS), we developed a new combined system with real-time "modified competitive oligonucleotide priming"-polymerase chain reaction (mCOP-PCR) and PCR restriction fragment length polymorphism (PCR-RFLP). Although our real-time mCOP-PCR method is secured enough to be gene-specific, its amplification efficiency is not as good because the reverse primers carry a nucleotide mismatched with the sequence of the pre-amplified product. The mismatch has consequently been generated in the process of introducing a restriction enzyme site in the pre-amplified products for PCR-RFLP., Method: DBS samples of the subjects were stored at room temperature for a period of less than one year. Each subject had already been genotyped by the first PCR-RFLP using fresh blood DNA. SMN1/SMN2 exon 7 was collectively amplified using conventional PCR (targeted pre-amplification). Pre-amplified products were used as template in the real-time mCOP-PCR, and, on the other hand, were digested with DraI enzyme (PCR-RFLP). To improve the amplification efficiency of mCOP-PCR, one nucleotide change was introduced in the original reverse primers (SMN1-COP and SMN2-COP) to eliminate the mismatched nucleotide., Results: The real-time mCOP-PCR with a new primer (SMN1-COP-DRA or SMN2-COP-DRA) more rapidly and specifically amplified SMN1 and SMN2, and clearly demonstrated SMN1 deletion in an SMA patient. With the new primers, the amplification efficiencies of real-time mCOP-PCR were improved and the Cq values of SMN1 (+) and SMN2 (+) samples were significantly lowered., Conclusion: In the advanced version of our screening system for homozygous SMN1 deletion using DBS, the real-time mCOP-PCR with newly-designed reverse primers demonstrated the presence or absence of SMN1 and SMN2 within a shorter time, and the results were easily tested by PCR-RFLP. This rapid and accurate screening system will be useful for detection of newborn infants with SMA.

Background: Spinal Muscular Atrophy (SMA) is a common autosomal recessive neuromuscular disorder characterized by degeneration or loss of lower motor neurons. More than 95% of SMA patients show homozygous deletion for the survival motor neuron 1 (SMN1) gene. For the screening of SMN1 deletion, it is necessary to differentiate SMN1 from its highly homologous gene, SMN2. We developed a modified competitive oligonucleotide priming-PCR (mCOP-PCR) method using dried blood spot (DBS)-DNA, in which SMN1 and SMN2-specific PCR products are detected with gel-electrophoresis. Next, we added a targeted pre-amplification step prior to the mCOP-PCR step, to avoid unexpected, non-specific amplification. The pre-amplification step enabled us to combine mCOP-PCR and real-time PCR. In this study, we combined real-time mCOP-PCR and PCR-restriction fragment length polymorphism (PCR-RFLP) to develop a new screening system for detection of SMN1 deletion., Methods: DBS samples of the subjects were stored at room temperature for a period of less than one year. Each subject had already been genotyped by the first PCR-RFLP using fresh blood DNA. SMN1/SMN2 exon 7 was collectively amplified using conventional PCR (targeted pre-amplification), the products of which were then used as a template in the real-time PCR with mCOP-primer sets. To confirm the results, the pre-amplified products were subject to the second PCR-RFLP., Results: The real-time mCOP-PCR separately amplified SMN1 and SMN2 exon7, and clearly demonstrated SMN1 deletion in an SMA patient. The results of the real-time mCOP-PCR using DBS-DNA were completely consistent with those of the first and second PCR-RFLP analysis., Conclusion: In our new system for detection of SMN1 deletion, real-time mCOP-PCR rapidly proved the presence or absence of SMN1 and SMN2, and the results were easily tested by PCR-RFLP. This solid genotyping system will be useful for SMA screening.

Background: Spinal Muscular Atrophy (SMA) is a common autosomal recessive disorder caused by SMN1 gene deletion. SMA has been considered an incurable disease. However, a newly-developed antisense oligonucleotide drug, nusinersen, brings about a good outcome to SMA patients in the clinical trials. Now, a screening for SMA is required for early diagnosis and early treatment so as to give a better clinical outcome to the patients. We have invented a new technology, mCOP-PCR, for SMA screening using dried blood spot (DBS) on the filter paper. One of the problems encountered in SMA screening is poor quality and quantity of DNA extracted from DBS., Methods: DNA was extracted from DBS of six individuals. Fresh blood DNA of each individual had already been genotyped using PCR/RFLP. The fragments including the sequence of SMN1/SMN2 exon 7 were pre-amplified with conventional PCR. To determine which pre-amplified product is a better template for the real-time mCOP-PCR, we did pre-amplification with a single PCR or pre-amplification with a nested PCR., Results: The real-time mCOP-PCR using pre-amplified products with a single PCR brought about ambiguous results in some SMN1-carrying individuals. However, the results of real-time mCOP-PCR following pre-amplification with a nested PCR were completely matched with those of PCR-RFLP., Conclusion: In our study on the real-time mCOP-PCR screening system for SMA, a nested PCR secured the DNA template quality and quantity, leading to unambiguous results of SMA screening.

The nasal cellular epigenome may serve as biomarker of airway disease and environmental response. Here we collect nasal swabs from the anterior nares of 547 children (mean-age 12.9 y), and measure DNA methylation (DNAm) with the Infinium MethylationEPIC BeadChip. We perform nasal Epigenome-Wide Association analyses (EWAS) of current asthma, allergen sensitization, allergic rhinitis, fractional exhaled nitric oxide (FeNO) and lung function. We find multiple differentially methylated CpGs (FDR < 0.05) and Regions (DMRs; ≥ 5-CpGs and FDR < 0.05) for asthma (285-CpGs), FeNO (8,372-CpGs; 191-DMRs), total IgE (3-CpGs; 3-DMRs), environment IgE (17-CpGs; 4-DMRs), allergic asthma (1,235-CpGs; 7-DMRs) and bronchodilator response (130-CpGs). Discovered DMRs annotated to genes implicated in allergic asthma, Th2 activation and eosinophilia (EPX, IL4, IL13) and genes previously associated with asthma and IgE in EWAS of blood (ACOT7, SLC25A25). Asthma, IgE and FeNO were associated with nasal epigenetic age acceleration. The nasal epigenome is a sensitive biomarker of asthma, allergy and airway inflammation.

This study explored Pholiota nameko (P. nameko) polysaccharide fractions, PNP-40, PNP-60, and PNP-80, purified by gradient concentrations of ethanol (40%, 60%, and 80% (v/v)). The physicochemical properties, functional group composition, moisture-preserving, and antioxidant ability were determined. The results indicate that the polysaccharide contents of PNP-40, PNP-60, and PNP-80 are 45.12%, 78.04%, and 72.22%, respectively, while the β-glucan, protein, and uronic acid contents are 20.20%, 12.20%, and 10.15%, respectively; 11.24%, 14.53%, and 26.94%; and 5.99%, 7.73%, and 3.78%. Furthermore, PNP-60 has better moisture absorption, while PNP-80 has better antioxidant ability and H 2 O 2 -injury resistance activity. Monosaccharide composition analysis shows that P. nameko belongs to heteropolysaccharides, which consists of galactose, glucose, and mannose with different types and ratios, and the molecular weight are distributed at 4.40-333.49kDa. It was found that different polysaccharide fractions have the potential to be a moisturizer and an antioxidant, and their active ingredients could be used in the development of cosmetic ingredients., (Copyright © 2019. Published by Elsevier B.V.)

This Special Issue on Clinical Genetics in Asia highlights a collection of articles showing the growth, development, and current status of clinical genetics in Asia. In this Introduction, the Guest Editors share on the themes of this issue to provide useful insights into the rapid growth of genomics and clinical genetics in this region. The contents of this Issue cover a range of topics from the history and development of clinical genetics in Asia to studies on disorders with clinical significance or phenotype differences in the Asian populations to the status of precision medicine. The goal is to provide a glimpse of how significantly the field of genetics in Asia has developed in recent years with the aspiration that this can serve as a catalyst to increase international collaboration and cooperation in combating genetic diseases. We hope that this issue shows Asia's readiness and willingness to be a part of more international conversations about genetics in future., (© 2019 Wiley Periodicals, Inc.)

Putting together the reports in this issue that come from a representation of the different countries in Asia presents an opportunity to share the unique story of the Asia Pacific Society of Human Genetics (APSHG), which has provided the authors of many of these articles. This paper, authored by the Past Presidents of the Society, shares glimpses of how medical genetics activities were first organized in the Asia Pacific region and provides interesting corollaries on how under-developed and developing countries in this part of the world had developed a unique network for exchange and sharing of expertise and resources. Although APSHG was formally registered as a Society in Singapore in 2006, the Society has its origins as far back as in the 1990s with members from different countries meeting informally, exchanging ideas, and collaborating. This treatise documents the story of the experiences of the Society and hopes it will provide inspiration on how members of a genetics community can foster and build a thriving environment to promote this field., (© 2019 Wiley Periodicals, Inc.)

Background: Home fungus exposures may be associated with development or worsening of asthma. Little is known about the effects of school/classroom fungus exposures on asthma morbidity in students., Objective: To evaluate the association of school-based fungus exposures on asthma symptoms in both fungus-sensitized and nonsensitized students with asthma., Methods: In this prospective study, 280 children with asthma from 37 inner-city schools were phenotypically characterized at baseline and followed-up for 1 year. Fungal spores were collected by using a Burkard air sampler twice during the school year. Clinical outcomes were evaluated throughout the school year and linked to classroom-specific airborne spore sampling. The primary outcome was days with asthma symptoms per 2-week period., Results: Fungal spores were present in all classroom samples. The geometric mean of the total fungi was 316.9 spores/m 3 and ranged from 15.0 to 59,345.7 spores/m 3 . There was variability in total fungus quantity between schools and classrooms within the same school. Mitospores were the most commonly detected fungal grouping. Investigation of the individual mitospores revealed that exposure to Alternaria was significantly associated with asthma symptom days in students sensitized to Alternaria (OR = 3.61, CI = 1.34-9.76, P = .01), but not in children not sensitized to Alternaria (OR = 1.04, CI = 0.72-1.49, P = .85). Students sensitized to Alternaria and exposed to high levels (≥75th percentile exposure) had 3.2 more symptom days per 2-week period as compared with students sensitized but exposed to lower levels., Conclusion: Children with asthma who are sensitized to Alternaria and exposed to this fungus in their classroom may have significantly more days with asthma symptoms than those who were sensitized and not exposed., Clinical Trial Registration: Clinicaltrials.govNCT01756391., (Copyright © 2019 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Duchenne and Becker muscular dystrophies (DMD/BMD) are X-linked recessive disorders caused by mutations in the DMD gene. Emerging therapies targeting patients with specific mutations are now becoming a reality for many of these patients. Precise molecular diagnosis is essential to facilitate the identification of possible new treatments for patients in the local context. In this study, we screened 145 dystrophinopathic patients in Singapore and assessed their molecular status for eligibility to current emerging genetic therapies. Overall, 140 (96.5%) of all patients harbored pathogenic DMD mutations comprising 95 exonic deletions (65.5%), 14 exonic duplications (9.7%), and 31 pathogenic small mutations (21.4%). Nonsense and frameshift mutations constitute 83.9% of all the small mutations. We found 71% (103/145) of all Singaporean dystrophinopathy patients to be theoretically amenable for exon skipping, either through skipping of single (53.1%) or multiple exons (17.9%). This approach is applicable to 81.1% (77/95) of patients carrying deletions and 83.9% (26/31) of those with small mutations. Eteplirsen induced skipping of exon 51 is applicable to 12.4% of local patients. Nonsense read-through therapy was found to be applicable in another 12.4% of all patients. Mutation screening is crucial for providing insights into the underlying genetic signature of the disease in the local population and contributes toward existing information on DMD mutations in Asia and globally. This will guide future targeted drug development and clinical trial planning for this disease., (© 2019 Wiley Periodicals, Inc.)

The status of training in clinical genetics and genetic counseling in Asia is at diverse stages of development and maturity. Most of the training programs are in academic training centers where exposure to patients in the clinics or in the hospital is a major component. This setting provides trainees with knowledge and skills to be competent geneticists and genetic counselors in a variety of patient care interactions. Majority of the training programs combine clinical and research training which provide trainees a broad and integrated approach in the diagnosis and management of patients while providing opportunities for research discoveries that can be translated to better patient care. The background on how the training programs in clinical genetics and genetic counseling in Asia evolved to their current status are described. Each of these countries can learn from each other through sharing of best practices and resources., (© 2019 Wiley Periodicals, Inc.)

Near-infrared (NIR)-based nanomaterials that provide efficient tumor ablation for cancer therapy have been reported. However, the issues of biocompatibility of metals or ions in inorganic nanoparticles systems such as copper and gold nanoparticles are still a matter of concern. In this study, we developed a facile and ligand-assisted co-precipitation method to synthesize biocompatible iron oxide (IO) nanocrystals with NIR absorption that provided T2-weighted magnetic resonance (MR) images and photothermal ablation characteristics suitable for cancer theranostics. Our results showed that 150-nm particles can be synthesized and optimized by using different amounts of ligand. NIR-IO nanocrystals of this size showed high photothermal conversion efficiency (21.2%) and T2-weighted MR contrast (transverse relaxivity value approximately 141 S-1 mM-1). The NIR-IO nanocrystals showed no cytotoxicity in HT-29 colorectal cancer cells without irradiation, whereas the viability of cells that received NIR-IO nanocrystals decreased significantly after 808-nm laser irradiation. The mechanism of cell death may involve alterations in protein secondary structure and membrane permeability. For in vivo studies, 4-fold enhanced tumor accumulation was significantly observed of NIR-IO nanocrystals with a magnetic field (MF) application, resulting in a 3-fold higher T2-weighted MR signal than that produced by a commercial T2-weighted MR contrast agent (Resovist®) and excellent photothermal efficacy (approximately 53 °C) for cancer treatment. The innovative NIR-IO nanocrystals showed excellent biocompatibility and have great potential as a theranostic agent against cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

In a rapidly greying world, the notion that some individuals maintain successful aging trajectories, viz. high physical, cognitive, emotional, and social functioning in older age, is increasingly germane. Biomarkers of such successful aging are increasingly sought. Leukocyte telomere length (LTL), an emerging yardstick of cellular aging that is influenced by but distinct from chronological age, may also be associated to successful aging. Furthermore, given that socio-economic status (SES) influences successful aging trajectories, socioeconomic status may also moderate the association between chronological age and LTL. The goals of this study are to examine 1) whether successful aging is associated with LTL; 2) whether successful aging accounts for age-related LTL and 3) whether SES moderates the effect of age on LTL. Singaporean Chinese (n = 353) aged 65-80 completed a multidimensional assessment of successful aging and provided blood samples for LTL analysis. Results show that LTL negatively correlates with chronological age and positively correlates with successful aging. Successful aging mediates the association between chronological age and LTL. Moderated mediation analyses show that lower SES is associated with stronger negative associations of chronological age with successful aging and LTL. Moreover, the cognitive functioning dimension of successful aging is uniquely associated with LTL and its association with chronological age is moderated by SES. This study provides evidence that among older Singaporean Chinese with lower SES, declines in successful aging and in cognitive functioning are linked to age-related LTL shortening and hence to accelerated aging at the cellular level., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Cancer has become one of the major diseases of human health around the world. Conventional antitumor drugs cannot specifically target cancers and result in serious side effects. To achieve better therapy, innovative functional drug delivery platforms that will aid specific targeting for cancer cells need to be developed. In this study, transferrin (Tf), which can target cancer cells, is covalently anchored onto the surface of MSNPs via disulfide linkage, which is used for glutathione-triggered intracellular drug release in tumor cells. The successful functionalization of redox-responsive MSNPs is confirmed by using BET/BJH, TEM, TGA, NMR, and FT-IR (BET, Brunauer-Emmett-Teller; BJH, Barrett-Joyner-Halenda). In addition, polyethylene glycol (PEG) is further grafted onto the surface of MSNPs to improve the biocompatibility and stability under physiological conditions for longer blood circulation. Our in vitro studies demonstrate that DOX-loaded MSNP-SS-Tf@PEG can selectively be internalized into cancer cells via Tf/Tf receptor interactions, and then, DOX is released in HT-29 and MCF-7 cells triggered by high GSH concentration in tumor cells. Remarkably, in vivo studies demonstrate that DOX-loaded MSNP-SS-Tf@PEG can significantly inhibit tumor growth with minimized side effects through cell apoptosis determined by TUNEL assay, whereas MSNP-SS-Tf@PEG revealed no significant inhibition. In conclusion, DOX-MSNP-SS-Tf@PEG with active targeting moieties and a redox-responsive strategy has been demonstrated as a great effective drug carrier for tumor therapy in vitro and in vivo .

Background: In the application of scientific human skeletal variation in medico-legal matters, virtual anthropology is the current technique performed to examine skeleton and its body parts. Hence, this study was conducted to assess the accuracy and reliability of virtual femur measurement through intra and inter-observer error analysis, and comparison was made between the virtual and conventional methods., Methods: A total of 15 femora were examined with four parameters i.e. maximum length of femur (FeMl), diameter of femoral head (FeHd), transverse diameter of midshaft (FeMd) and condylar breadth (FeCb). Osteometric board and vernier calipers were employed for the conventional method, while CT reconstructed images and Osirix MD software was utilised for the virtual method., Results: Results exhibited that there were no significant differences in the measurements by conventional and virtual methods. There were also no significant differences in the measurements by the intra or inter-observer error analyses. The intraclass correlation coefficients (ICC) were more than 0.95 by both intra and inter-observer error analyses. Technical error of measurement had displayed values within the acceptable ranges (rTEM <0.08 for intra-observer, <2.25 for inter-observer), and coefficient of reliability (R) indicated small measurement errors (R > 0.95 for intra-observer, R > 0.92 for inter-observer). By parameters, FeMl showed the highest R value (0.99) with the least error in different methods and observers (rTEM = 0.02-0.41%). Bland and Altman plots revealed points scattered close to zero indicating perfect agreement by both virtual and conventional methods. The mean differences for FeMl, FeHd, FeMd and FeCb measurements were 0.01 cm, -0.01 cm, 0.02 cm and 0.01 cm, respectively., Conclusion: This brought to suggest that bone measurement by virtual method was highly accurate and reliable as in the conventional method. It is recommended for implementation in the future anthropological studies especially in countries with limited skeletal collection., (Copyright © 2019 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

Purpose of Review: Recent evidence suggests that environmental exposures change the adult human microbiome. Here, we review recent evidence on the impact of the work microbiome and work-related chemical, metal and particulate exposures on the human microbiome., Recent Findings: Prior literature on occupational microbial exposures has focused mainly on the respiratory effects of endotoxin, but a recent study suggests that not all endotoxin is the same; endotoxin from some species is proinflammatory, whereas endotoxin from other species is anti-inflammatory. Work with animals can change the adult human microbiome, likely through colonization. Early studies in military personnel and animal models of gulf war illness show that military exposures change the gut microbiome and increase gut permeability. Heavy metal and particulate matter exposure, which are often elevated in occupational settings, also change the gut microbiome., Summary: An emerging body of literature shows that work-related exposures can change the human microbiome. The health effects of these changes are currently not well studied. If work exposures lead to disease through alterations in the human microbiome, exposure cessation without addressing changes to the human microbiome may be ineffective for disease prevention and treatment.

Combinatory modulation of the physical and biochemical characteristics of nanocarrier delivery systems is an emergent topic in the field of nanomedicine. Here, we studied the combined effects of incorporation of active targeting moieties into nanocarriers and their morphology affecting the enhanced permeation and retention effect for nanomedicine cancer therapy. Self-assembled lipid discoidal and vesicular nanoparticles with low-polydispersity sub-50 nm size range and identical chemical compositions were synthesized, characterized, and correlated with in vitro cancer cellular internalization, in vivo tumor accumulation and cancer treatments. The fact that folate-associated bicelle yields the best outcome is indicative of the preference for discoidal carriers over spherical carriers and the improved targeting efficacy due to the targeting ligand/receptor binding. The approach is successfully adopted to design the nanocarriers for photodynamic therapy, which yields a consistent trend in in vitro and in vivo efficacy: folate nanodiscs > folate vesicles > nonfolate nanodiscs > nonfolate vesicles. Folate discs not only have shown a higher tumor uptake and photothermal therapeutic efficiency, but also minimize skin photosensitivity side effects. The advantages of nanodiscoidal bicelles as nanocarriers, including well-defined size, robust formation, easy encapsulation of hydrophobic molecules (therapeutics and/or diagnostics), easy incorporation of targeting molecules, and low toxicity, enable the scalable manufacturing of a generalized in vivo multimodal delivery platform.

The mechanism of hepatoprotective compounds is usually related to its antioxidant or anti-inflammatory effects. Black garlic is produced from garlic by heat treatment and its anti-inflammatory activity has been previously reported. Therefore, the aim of this study was to investigate the hepatoprotective effect of five different extracts of black garlic against carbon tetrachloride (CCl₄)-induced acute hepatic injury (AHI). In this study, mice in the control, CCl₄, silymarin, and black garlic groups were orally administered distilled water, silymarin, and different fraction extracts of black garlic, respectively, after CCl₄ was injected intraperitoneally to induce AHI. The results revealed that the n -butanol layer extract (BA) and water layer extract (WS) demonstrated a hepatoprotective effect by reducing the levels of alanine aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and hepatic malondialdehyde (MDA). Furthermore, the BA and WS fractions of black garlic extract increased the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rd), tumor necrosis factor alpha (TNF-α), and the interleukin-1 (IL-1β) level in liver. It was concluded that black garlic exhibited significant protective effects on CCl₄-induced acute hepatic injury., Competing Interests: The authors declare no conflict of interest.

Oxytocin (OT) plays a salient role in contributing to the high levels of human sociality that characterize our species. Across the lifespan this nonapeptide promotes prosocial behaviors and modulates stress responses. Curiously, the OXT-Neurophysin I gene has been little studied despite the fact this is the structural gene for the OT nonapeptide. In a large group of Han Chinese undergraduate students (n = 1593) we examined associations of two single nucleotide polymorphisms of the OXT- Neurophysin I gene with personality traits. Results indicated that the OXT-Neurophysin I rs2770378 was related to extraversion, agreeableness, and neuroticism. AA homozygous individuals reported more prosocial personality traits, compared to participants carrying the G allele. These results indicate that variants of the OXT-Neurophysin-I gene resonate with phenotypes that foster positive social interactions, which may in turn facilitate the social regulation of stress responses., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The controlled size and surface treatment of magnetic nanoparticles (NPs) make one-stage combination feasible for enhanced magnetic resonance imaging (MRI) contrast and effective hyperthermia. However, superparamagnetic behavior, essential for avoiding the aggregation of magnetic NPs, substantially limits their performance. Here, a superparamagnetic core-shell structure is developed, which promotes the formation of vortex-like intraparticle magnetization structures in the remanent state, leading to reduced dipolar interactions between two neighboring NPs, while during an MRI scan, the presence of a DC magnetic field induces the formation of NP chains, introducing increased local inhomogeneous dipole fields that enhance relaxivity. The core-shell NPs also reveal an augmented anisotropy, due to exchange coupling to the high anisotropy core, which enhances the specific absorption rate. This in vivo tumor study reveals that the tumor cells can be clearly diagnosed during an MRI scan and the tumor size is substantially reduced through hyperthermia therapy by using the same FePt@iron oxide nanoparticles, realizing the concept of theranostics., (© 2018 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Wound infection extends the duration of wound healing and also causes systemic infections such as sepsis, and, in severe cases, may lead to death. Early prevention of wound infection and its appropriate treatment are important. A photoreactive modified gelatin (GE-BTHE) was synthesized by gelatin and a conjugate formed from the 3,3',4,4'-benzophenone tetracarboxylic dianhydride (BTDA) and the 2-hydroxyethyl methacrylate (HEMA). Herein, we investigated the photocurable polymer solution (GE-BTHE mixture) containing GE-BTHE, poly(ethylene glycol) diacrylate (PEGDA), chitosan, and methylene blue (MB), with antimicrobial functions and photodynamic antimicrobial chemotherapy for wound dressing. This photocurable polymer solution was found to have fast film-forming property attributed to the photochemical reaction between GE-BTHE and PEGDA, as well as the antibacterial activity in vitro attributed to the ingredients of chitosan and MB. Our in vivo results also demonstrated that untreated wounds after 3 days had the same scab level as the GE-BTHE mixture-treated wounds after 20 s of irradiation, which indicates that the irradiated GE-BTHE mixture can be quickly transferred into artificial scabs to protect wounds from an infection that can serve as a convenient excisional wound dressing with antibacterial efficacy. Therefore, it has the potential to treat nonhealing wounds, deep burns, diabetic ulcers and a variety of mucosal wounds.

Background: The SMN genes, SMN1 and SMN2, are highly homologous genes which are related to the development or clinical severity of spinal muscular atrophy. Some alternative splicing patterns of the SMN genes have been well documented. In 2007, an SMN1 transcript with a full sequence of intron 3 was reported as the first intron-retained SMN transcript., Methods: Intron-retained SMN transcripts in various cells and tissues were studied using reverse transcription (RT)-PCR. HeLa cells were used for subcellular localization of the transcripts and protein expression analysis with Western blotting., Results: Two intron-retained SMN transcripts were detected, which contain full sequences of intron 2b or intron 3. These transcripts were produced from SMN1 and SMN2, and ubiquitously expressed in human cells and tissues. Western blotting analysis showed no proteins derived from the intron-retained transcripts. Fractionation analysis showed that these intron-retained transcripts were localized mainly in the nucleus. Contrary to our expectation, the intron-retained transcript levels decreased during the treatment of cycloheximide, an inhibitor of nonsense-mediated decay (NMD), suggesting that they were not targets of NMD., Conclusion: Intron 2b-retained SMN transcript and intron3-retained SMN transcript were ubiquitously expressed in human cells and tissues. The intron-retained transcripts were mainly localized in the nucleus and decreased through non-NMD pathway., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Cadaver body bags are the conventional method to contain a human body or human remains, which includes the use for storage and transportation of the deceased at any crime scene or disaster scene. During disasters, most often than not, the first responders including the police will be equipped with cadaver body bags to do scene processing of human remains and collection of personal belongings at the disaster site. However, in an unanticipated large scale disasters involving hundreds and thousands of fatalities, cadaver body bags supplies may be scarce. The authors have therefore innovated the cling film plastic wrap as an alternative for the cadaver body bag used at the disaster site. The plastic wrap was tested on six different experimental subjects, i.e. both adult and child mannequins; body parts of the mannequin figure (arm and hand); a human adult subject and an unknown dead body. The strengths of the cling film plastic wrap are discussed in comparison with the cadaver body bag in the aspects of costing, weight, duration of the wrap, water and body fluid resistant properties, visibility and other advantages. An average savings of more than 5000% are noted for both adult body wrap and child body wrap compared to the cadaver body wrap. This simply means that the authors can either wrap 25 adult dead bodies or 80 children dead bodies with the cost of 1 cadaver body bag. The cling film plastic wrap has proven to have significant innovation impact for dead body management particularly by the first responders in large scale disasters. With proper handling of dead bodies, first responders can manage the dead with dignity and respect in an overwhelmed situation to facilitate the humanitarian victim identification process later., (Copyright © 2018 Elsevier B.V. All rights reserved.)