Incidence of Interstitial Lung Abnormalities: The MESA Lung Study.

The incidence of newly developed interstitial lung abnormalities (ILA) and fibrotic ILA have not been previously reported.Trained thoracic radiologists evaluated 13 944 cardiac CT scans for the presence of ILA in 6197 Multi-Ethnic Study of Atherosclerosis longitudinal cohort study participants >45 years of age from 2000 to 2012. 5% of the scans were re-read by the same or a different observer in a blinded fashion. After exclusion of participants with ILA at baseline, incidence rates and incidence rate ratios for ILA and fibrotic ILA were calculated.The intra-reader agreement of ILA was 92.0% (Gwet AC1=0.912, ICC=0.982) and the inter-reader agreement of ILA was 83.5% (Gwet AC1=0.814; ICC=0.969). Incidence of ILA and fibrotic ILA was estimated to be 13.1 cases/1000 person-years and 3.5/1000 person-years, respectively. In multivariable analyses, age (HR 1.06 (1.05, 1.08), p <0.001; HR 1.08 (1.06, 1.11), p <0.001), high attenuation area (HAA) at baseline (HR 1.05 (1.03, 1.07), p <0.001; HR 1.06 (1.02, 1.10), p=0.002), and the MUC5B promoter SNP (HR 1.73 (1.17, 2.56) p=0.01; HR 4.96 (2.68, 9.15), p <0.001) were associated with incident ILA and fibrotic ILA, respectively. Ever smoking (HR 2.31 (1.34, 3.96), p= 0.002) and an IPF polygenic risk score (HR 2.09 (1.61-2.71), p<0.001) were associated only with incident fibrotic ILA.Incident ILA and fibrotic ILA were estimated by review of cardiac imaging studies. These findings may lead to wider application of a screening tool for atherosclerosis to identify preclinical lung disease.

Effect of digestion on stability of palivizumab IgG1 in the infant gastrointestinal tract.

BACKGROUND: Potentially, orally administered antibodies specific to enteric pathogens could be administered to infants to prevent diarrheal infections, particularly in developing countries where diarrhea is a major problem. However, to prevent infection, such antibodies would need to resist degradation within the gastrointestinal tract. METHODS: Palivizumab, a recombinant antibody specific to respiratory syncytial virus (RSV), was used in this study as a model for examining the digestion of neutralizing antibodies to enteric pathogens in infants. The survival of this recombinant IgG1 across digestion in 11 infants was assayed via an anti-idiotype ELISA and RSV F protein-specific ELISA. Concentrations were controlled for any dilution or concentration that occurred in the digestive system using mass spectrometry-based quantification of co-administered, orally supplemented, indigestible polyethylene glycol (PEG-28). RESULTS: Binding activity of Palivizumab IgG1 decreased (26-99%) across each phase of in vivo digestion as measured by both anti-idiotype and RSV F protein-specific ELISAs. CONCLUSION: Antibodies generated for passive protection of the infant gastrointestinal tract from pathogens will need to be more resistant to digestion than the model antibody fed to infants in this study, or provided in higher doses to be most effective. IMPACT: Binding activity of palivizumab IgG1 decreased (26-99%) across each phase of in vivo infant digestion as measured by both anti-idiotype and RSV F protein-specific ELISAs. Palivizumab was likely degraded by proteases and changes in pH introduced in the gut. Antibodies generated for passive protection of the infant gastrointestinal tract from pathogens will need to be more resistant to digestion than the model antibody fed to infants in this study, or provided in higher doses to be most effective. The monoclonal antibody IgG1 tested was not stable across the infant gastrointestinal tract. The observation of palivizumab reduction was unlikely due to dilution in the gastrointestinal tract. The results of this work hint that provision of antibody could be effective in preventing enteric pathogen infection in infants. Orally delivered recombinant antibodies will need to either be dosed at high levels to compensate for digestive losses or be engineered to better resist digestion. Provision of enteric pathogen-specific recombinant antibodies to at-risk infants could provide a new and previously unexplored pathway to reducing the infection in infants. The strategy of enteric recombinant antibodies deserves more investigation throughout medicine as a novel means for treatment of enteric disease targets.

Design of a 3D printed smartphone microscopic system with enhanced imaging ability for biomedical applications.

Portable, low-cost smartphone platform microscopic systems have emerged as a potential tool for imaging of various micron and submicron scale particles in recent years (Ozcan; Pirnstill and Coté; Breslauer et al.; Zhu et al.). In most of the reported works, it involves either the use of sophisticated optical set-ups along with a high-end computational tool for postprocessing of the captured images, or it requires a high-end configured smartphone to obtain enhanced imaging of the sample. Present work reports the working of a low-cost, field-portable 520× optical microscope using a smartphone. The proposed smartphone microscopic system has been designed by attaching a 3D printed compact optical set-up to the rear camera of a regular smartphone. By using cloud-based services, an image processing algorithm has been developed which can be accessed anytime through a mobile broadband network. Using this facility, the quality of the captured images can be further enhanced, thus obviating the need for dedicated computational tools for postprocessing of the images. With the designed microscopic system, an optical resolution ∼2 µm has been obtained. Upon postprocessing, the resolution of the captured images can be improved further. It is envisioned that with properly designed optical set-up in 3D printer and by developing an image processing application in the cloud, it is possible to obtain a low-cost, user-friendly, field-portable optical microscope on a regular smartphone that performs at par with that of a laboratory-grade microscope. LAY DESCRIPTION: With the ever-improving features both in hardware and software part, smartphone becomes ubiquitous in the modern civilised society with approximately 8.1 billion cell phone users across the world, and ∼40% of them can be considered as smartphones. This technology is undoubtedly the leading technology of the 21st century. Very recently, various researchers across the globe have utilised different sensing components embedded in the smartphone to convert it into a field-portable low-cost and user-friendly tool which can be used for different sensing and imaging purposes. By using simple optical components such as lens, pinhole, diffuser etc. and the camera of the smartphone, various groups have converted the phone into a microscopic imaging system. Again, by removing the camera lenses of the phone, holography images of microscopic particles by directly casting its shadows on the CMOS sensor on the phone has been demonstrated. The holographic images have subsequently been processed using the dedicated computational tool, and the original photos of the samples can be obtained. All the reported smartphone-based microscopic systems either suffer from relatively low field-of-view (FOV), resolution or it needs a high computational platform. Present work, demonstrate an alternative approach by which a reasonably good resolution (<2 µm) along with high optical magnification (520×) and a large FOV (150 µm) has been obtained on a regular smartphone. For postprocessing of the captured images an image processing algorithm has been developed in the cloud and the same can be accessed by the smartphone application, obviating the need of dedicated computational tool and a high-end configured smartphone for the proposed microscope. For the development of the proposed microscopic system, a simple optical set-up has been fabricated in a 3D printer. The set-up houses all the required optical components and the sample specimen with the 3D-printed XY stage, and it can be attached easily to the rear camera of the smartphone. Using the proposed microscopic system, enhanced imaging of USAF target and red blood cells have been successfully demonstrated. With the readily available optical components and a regular smartphone, the net cost involvement is significantly low (less than $250, including the smartphone). We envisioned that the designed system could be utilised for point-of-care diagnosis in resource-poor settings where access to the laboratory facilities is very limited.

Characterization and in silico proteomic analysis of C2 and C3 proteins of squash leaf curl China virus associated with pumpkin leaf curl disease in Assam, India.

The pumpkin leaf curl disease is an emerging disease of pumpkin in Assam, India. Symptomatic pumpkin leaf samples from different locations were immunologically tested using Begomovirus specific antibody. PCR with the ELISA-positive samples, using Geminivirus universal primers amplified 1.4 kb virus-specific fragments. Sequence of these amplicons showed around 95% identity with squash leaf curl China virus-[Pumpkin: Varanasi] (SLCCV-Pumpkin: Varanasi EU573715). To investigate the possible functions of the viral proteins present in the fragment, the full-length C2 and C3 genes were conceptually translated and were subjected to in silico proteomic analyses. The phylogenetic analysis of both the proteins divulged the relationship of our isolate with related viruses and isolates. Multiple sequence alignment (MSA) of the proteins revealed the presence of the known viral conserved motifs, viz., zinc-finger (ZNF) motif [36CXCX(7)CX(6)H53], the arginine-rich nuclear localization signal (NLS) motif (28RRRR31) as well as the minimal activation domain in C2 protein. In the C3 protein, the 91LKYLD95 and the replication enhancer motif (30YFK32) were found to be conserved. Finally, 3-D models of the two proteins were predicted via ab initio approach and subsequently, the models were validated. To our knowledge, this study is a pioneering attempt to construct the ab initio 3-D models of two begomoviral proteins taking a SLCCV isolate as a model. Keywords: begomovirus; ELISA; ZNF motif; NLS motif; ab initio modelling.

Fabrication of flexible thin polyurethane membrane for tissue engineering applications.

Thin and flexible polymeric membranes play a critical role in tissue engineering applications for example organs-on-a-chip. These flexible membranes can enable mechanical stretch of the engineered tissue to mimic organ-specific biophysical features, such as breathing. In this work, we report the fabrication of thin (<20 µm), stretchable, and biocompatible polyurethane (PU) membranes. The membranes were fabricated using spin coating technique on silicon substrates and were mounted on a frame for ease of device integration and handling. The membranes were characterized for their optical and elastic properties and compatibility with cell/tissue culture. It was possible to apply up to 10 kilopascal (kPa) pressure to perform cyclic stretch on 4 mm-diameter membranes for a period of 2 weeks at 0.2 hertz (Hz) frequency without mechanical failure. Adenocarcinomic human alveolar basal epithelial (A549) cells were cultured on the apical side of the PU membrane. The morphology and viability of the cells were comparable to those of cells cultured on standard tissue culture plates. Our experiments suggest that the stretchable PU membrane will be broadly useful for various tissue engineering applications in vitro.

Lung Cancer Risk Associated With New Solid Nodules in the National Lung Screening Trial.

OBJECTIVE: As low-dose CT (LDCT) lung cancer screening moves into routine clinical practice, evaluation of nodules identified as new becomes critical. We examine the frequency and clinical outcomes of new lung nodules reported at the two postbaseline annual screening examinations (hereafter referred to as postbaseline time 1 [T1] and time 2 [T2]), compared with those detected at baseline in the National Lung Screening Trial. MATERIALS AND METHODS: Radiologists classified nodules detected at T1 and T2 as new or preexisting on the basis of comparison with findings from prior LDCT screening examinations. Subjects were tracked for lung cancer incidence and mortality. We examined the incidence of new nodules and their associated lung cancer risk by nodule size (i.e., mean diameter). RESULTS: A total of 25,002 subjects underwent the baseline LDCT screening examination and either a T1 or T2 LDCT screen. At both T1 and T2, 2.6% of subjects had new solid nodules. Of the new solid nodules, 53.0% were < 6 mm, 29.5% were 6 to < 10 mm, and 17.1% were ≥ 10 mm. Lung cancer risk (defined as diagnosis within 2 years of baseline) increased from 1.1% for nodules < 4 mm to 24.0% for those ≥ 20 mm. Compared with solid nodules detected at baseline, the cancer risk was higher for new solid nodules that were 4 to < 6 mm (p < 0.001) and 6 to < 8 mm (p < 0.001) but lower for new nodules ≥ 20 mm (p = 0.03). Cancers associated with new nodules had significantly poorer survival than did those associated with baseline nodules and were significantly less likely to be adenocarcinoma. CONCLUSION: The incidence of new nodules was 2-3% annually, with the cancer risk increasing by nodule size. New nodules may convey differential lung cancer risks by size, compared with baseline nodules.

Purification and development of ELISAs for two forms of vitellogenin in Indian walking catfish, Clarias batrachus (L.).

Two forms of vitellogenin (Vg: Vg1 and Vg2) were purified from the plasma of estradiol-17ß (E2)-treated Indian walking catfish, Clarias batrachus, by gel filtration and adsorption chromatography. Native Vg1 and Vg2 had apparent molecular masses of 375 and 450 kDa, respectively, and both Vgs resolved into two similar major bands (95 and 67 kDa) in SDS-PAGE under reducing condition. Polyclonal antisera raised against each form of Vg were absorbed with a combination of hypophysectomized male catfish serum proteins and alternate Vg to ensure specificity. Immunological analyses verified the presence of Vg1 and Vg2 in the plasma of female catfish. Homologous ELISAs were developed for Vg1 and Vg2 using their respective harvested antisera, which exhibited the detection limit of 100 ng ml-1 for Vg1 and 40 ng ml-1 for Vg2, and low level of cross-reactivity (not parallel to the standard) was found with alternate Vg in each assay. Treatment of male catfish with E2 induced both Vgs showing a proportionate ratio of Vg1 to Vg2 at 5.6:1. Plasma concentrations of both Vgs measured by ELISAs at different reproductive phases of field collected female catfish increased in accordance with the ovarian development, keeping the proportionate ratio of Vg1 to Vg2 at about 2:1 in fish undergoing vitellogenesis during prespawning period and 1:20 during spawning period, suggesting that Vg1 may be the major Vg to contribute in yolk formation, whereas Vg2, besides its role in yolk formation, may facilitate other physiological functions. The present study, thus, demonstrates the occurrence of two unequally synthesized Vgs in the catfish.

Rheumatoid arthritis-associated autoantibodies and subclinical interstitial lung disease: the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Adults with interstitial lung disease (ILD) often have serologic evidence of autoimmunity of uncertain significance without overt autoimmune disease. We examined associations of rheumatoid arthritis (RA)-associated antibodies with subclinical ILD in community-dwelling adults. METHODS: We measured serum rheumatoid factor (RF) and anticyclic citrullinated peptide antibody (anti-CCP) and high attenuation areas (HAAs; CT attenuation values between -600 and -250 Hounsfield units) on cardiac CT in 6736 community-dwelling US adults enrolled in the Multi-Ethnic Study of Atherosclerosis. We measured interstitial lung abnormalities (ILAs) in 2907 full-lung CTs at 9.5-year median follow-up. We used generalised linear and additive models to examine associations between autoantibodies and both HAA and ILA, and tested for effect modification by smoking. RESULTS: In adjusted models, HAA increased by 0.49% (95% CI 0.11% to 0.86%) per doubling of RF IgM and by 0.95% (95% CI 0.50% to 1.40%) per RF IgA doubling. ILA prevalence increased by 11% (95% CI 3% to 20%) per RF IgA doubling. Smoking modified the associations of both RF IgM and anti-CCP with both HAA and ILA (interaction p values varied from 0.01 to 0.09). Among ever smokers, HAA increased by 0.81% (95% CI 0.33% to 1.30%) and ILA prevalence increased by 14% (95% CI 5% to 24%,) per RF IgM doubling; and HAA increased by 1.31% (95% CI 0.45% to 2.18%) and ILA prevalence increased by 13% (95% CI 2% to 24%) per anti-CCP doubling. Among never smokers, no meaningful associations were detected. CONCLUSIONS: RA-related autoimmunity is associated with both quantitative and qualitative subclinical ILD phenotypes on CT, particularly among ever smokers.

High attenuation areas on chest computed tomography in community-dwelling adults: the MESA study.

Evidence suggests that lung injury, inflammation and extracellular matrix remodelling precede lung fibrosis in interstitial lung disease (ILD). We examined whether a quantitative measure of increased lung attenuation on computed tomography (CT) detects lung injury, inflammation and extracellular matrix remodelling in community-dwelling adults sampled without regard to respiratory symptoms or smoking.We measured high attenuation areas (HAA; percentage of lung voxels between -600 and -250 Hounsfield Units) on cardiac CT scans of adults enrolled in the Multi-Ethnic Study of Atherosclerosis.HAA was associated with higher serum matrix metalloproteinase-7 (mean adjusted difference 6.3% per HAA doubling, 95% CI 1.3-11.5), higher interleukin-6 (mean adjusted difference 8.8%, 95% CI 4.8-13.0), lower forced vital capacity (FVC) (mean adjusted difference -82 mL, 95% CI -119--44), lower 6-min walk distance (mean adjusted difference -40 m, 95% CI -1--80), higher odds of interstitial lung abnormalities at 9.5 years (adjusted OR 1.95, 95% CI 1.43-2.65), and higher all cause-mortality rate over 12.2 years (HR 1.58, 95% CI 1.39-1.79).High attenuation areas are associated with biomarkers of inflammation and extracellular matrix remodelling, reduced lung function, interstitial lung abnormalities, and a higher risk of death among community-dwelling adults.

Distribution of arbuscular mycorrhizal fungi associated with different land use systems of Arunachal Pradesh of Eastern Himalayan region.

Arbuscular mycorrhizal fungi are the main component of soil microbial population in most agroecosystems. They forms a close association with more than 80% of the plant species making immobilized mineral nutrients available to the plants in order to sustain normal growth and reproduction. In this study the diversity of mycorrhizal fungi has been examined in seven land use ecosystems of Arunachal Pradesh in Eastern Himalayan region. A total of 24 species of AM fungi belonging to 4 genera viz., Glomus, Scutellospora, Aculospora and Gigaspora were isolated from the soil samples collected from different land use systems. Glomus was the dominant genera and Glomus occulatum was the most abundant species in all the seven land use systems. Total spore number was highly variable among all the land use systems. Species richness was recorded highest in natural forest that maintains a faster nutrient cycle with the highest diversity index. The Jhum fallow land and tea garden has the least number of AM fungal species due to high disturbance of fire and application of fungicides and inorganic fertilizer. Further the plant species composition, particularly the ground vegetation coverage and disturbance level affects the distribution of the AM fungal species. In our study it has been shown that AMF diversity is significantly affected by the land use practices practiced by the people. Hence, the AM fungi isolated from different land use system may be useful in improving the agriculture practices particularly the plantation crops in the region.

Musculoskeletal disorder (MSD) among agricultural workers.

Farming is a large and main industry in Bangladesh. Large numbers of people are directly involved in farming and have very unique exposure compare to other sectors. Musculoskeletal problems among farmer population are not infrequent. This study was carried out among 200 farmers in one selected district. The study revealed that musculoskeletal problems were common among the farmers working in a traditional way. All the respondents were male. The age of all respondents lie between 20-60 years. Among them 22.5% farmers were illiterate, about 45.5% below Class V. About half (42%) of the respondents had reported pain in different parts of the body at least one or more times during working in land. And about two third (65.5%) of the farmers had history of joint pain and stiffness in last 12 month. Most of the farmers who suffered from musculoskeletal symptoms were 41-60 years. Specially who worked more then 20 years (82.6%) and average 6 hours per day (66.7%). The occurrence of musculoskeletal problems in various part of the body included Knee pain - 48.1%, Back pain (back ache) - 22.9%, Waist pain (low back ache) - 13.3%, Neck pain - 18.3% and shoulder pain - 10.7%. Length of work in year and daily average working hours were found significant association with musculoskeletal pain. It was found that musculoskeletal pain were more common among the farmers when they worked in squatting position (52%) and specially during weeding of plants (31%). Among them only 22% also engaged in other business. Most of the farmers complained dull aching pain (40.6%), only 2.3% noticed severe acute pain, but about 86% farmers' temporary stop their work for pain and 80% get relief after discontinue of work. About 75% respondents visited doctors for their pain which was statistically significant (p=0.001). It was found that the rates of musculoskeletal complaints are more among those individuals who worked relatively bad ergonomic condition, such as body position probably play an important role.

Digestive Profiles of Human Milk, Recombinant Human and Bovine Lactoferrin: Comparing the Retained Intact Protein and Peptide Release.

Lactoferrin (LF) is a major component of human milk. LF supplementation (currently bovine) supports the immune system and helps maintain iron homeostasis in adults. No recombinant human lactoferrin (rhLF) is available for commercial food use. To determine the extent to which rhLF (Effera™) produced by Komagataella phaffii digests similarly to hmLF, a validated in vitro digestion protocol was carried out. Bovine LF (bLF) was used as an additional control, as it is approved for use in various food categories. This study compared the extent of intact protein retention and the profile of peptides released in hmLF, bLF and rhLF (each with low and high iron saturation) across simulated adult gastric and intestinal digestion using gel electrophoresis, ELISA and LC-MS. Intact LF retention across digestion was similar across LF types, but the highest iron-saturated hmLF had greater retention in the simulated gastric fluid than all other sample types. Peptides identified in digested hmLF samples strongly correlated with digested rhLF samples (0.86 < r < 0.92 in the gastric phase and 0.63 < r < 0.70 in the intestinal phase), whereas digested bLF samples were significantly different. These findings support the potential for rhLF as a food ingredient for human consumption.

National lung screening trial: variability in nodule detection rates in chest CT studies.

PURPOSE: To characterize the variability in radiologists' interpretations of computed tomography (CT) studies in the National Lung Screening Trial (NLST) (including assessment of false-positive rates [FPRs] and sensitivity), to examine factors that contribute to variability, and to evaluate trade-offs between FPRs and sensitivity among different groups of radiologists. MATERIALS AND METHODS: The HIPAA-compliant NLST was approved by the institutional review board at each screening center; all participants provided informed consent. NLST radiologists reported overall screening results, nodule-specific findings, and recommendations for diagnostic follow-up. A noncalcified nodule of 4 mm or larger constituted a positive screening result. The FPR was defined as the rate of positive screening examinations in participants without a cancer diagnosis within 1 year. Descriptive analyses and mixed-effects models were utilized. The average odds ratio (OR) for a false-positive result across all pairs of radiologists was used as a measure of variability. RESULTS: One hundred twelve radiologists at 32 screening centers each interpreted 100 or more NLST CT studies, interpreting 72 160 of 75 126 total NLST CT studies in aggregate. The mean FPR for radiologists was 28.7% ± 13.7 (standard deviation), with a range of 3.8%-69.0%. The model yielded an average OR of 2.49 across all pairs of radiologists and an OR of 1.83 for pairs within the same screening center. Mean FPRs were similar for academic versus nonacademic centers (27.9% and 26.7%, respectively) and for centers inside (25.0%) versus outside (28.7%) the U.S. "histoplasmosis belt." Aggregate sensitivity was 96.5% for radiologists with FPRs higher than the median (27.1%), compared with 91.9% for those with FPRs lower than the median (P = .02). CONCLUSION: There was substantial variability in radiologists' FPRs. Higher FPRs were associated with modestly higher sensitivity.

Cervical mediastinoscopy: re-evaluation of an old technique in era of new imaging technology.

CONTEXT: With the advent of modern anatomical and functional imaging technologies, application of cervical mediastinoscopy has decreased in diagnosis and staging of mediastinal diseases. AIM: To evaluate the usefulness of cervical mediastinoscopy in assessing the mediastinal disease when imaging modalities are non-diagnostic. SETTINGS AND DESIGN: Retrospective analysis of records of a tertiary care hospital. PATIENTS AND METHODS: Thirty-nine patients with mediastinal pathology of varied aetiologies underwent cervical mediastinoscopy. Pre- and post-operative diagnosis was compared. RESULTS: In 34 out of 39 cases (87.5%), cervical mediastinoscopy provided a confirmatory final diagnosis. One case had a major complication in the form of recurrent laryngeal nerve palsy. CONCLUSION: Cervical mediastinoscopy is useful, minimally invasive modality in a scenario where anatomical and functional imaging tools are non-diagnostic.

Status of blood pressure among individuals consuming saline water.

Climate change is taking its toll in the form of saline water intrusion into the mainland of Bangladesh, which is one of the lowest-altitude countries in the world. The study was carried out with the objective to assess the blood pressure status associated with salinity in saline prone selected areas of Bagherhat and Tangail districts from March 2008 - June 2008 of rural Bangladesh. Two hundred and ninety subjects were selected purposively from both the districts. About 70% of the respondents were males and below forty years of age. More than two thirds of the respondents were illiterate; belong to 4-5 member family, with monthly family income of less than Tk. 4000 per month. Only one third of the respondents were smokers. More than two thirds of the respondents from salinity area had salinity level of 2-3%. Among them majority were drinking saline water for 6-10 years and 26% were drinking for more than ten years. About 20% of the non saline respondents' systolic blood pressure was 110-120 mm of Hg and 26% of saline area had systolic blood pressure >135-140 mm of Hg. Mean systolic BP among salinity area was more than that for non salinity area. About 19% of the non saline respondents' diastolic blood pressure was ≤ 85 mm of Hg. About one third had ≥ 90 mm of Hg, among them 31% were from saline area. Mean diastolic BP among salinity area was more than non salinity area. There was no history of heart disease, and less than 1% was diabetic among them. About two thirds had mean arterial pressure <70 mm of Hg, among them majority were from non saline area. About one third had >70 mm of Hg, among them majority were from saline area. The study concluded that systolic and diastolic blood pressures of saline group were significantly higher than that of the non saline group.