Contrasting gut bacteriomes unveiled between wild Antheraea assamensis Helfer (Lepidoptera: Saturniidae) and domesticated Bombyx mori L. (Lepidoptera: Bombycidae) silkworms.

BACKGROUND: Insect gut microbiomes play a fundamental role in various aspects of insect physiology, including digestion, nutrient metabolism, detoxification, immunity, growth and development. The wild Muga silkworm, Antheraea assamensis Helfer holds significant economic importance, as it produces golden silk. METHODS AND RESULTS: In the current investigation, we deciphered its intricate gut bacteriome through high-throughput 16S rRNA amplicon sequencing. Further, to understand bacterial community dynamics among silkworms raised under outdoor environmental conditions, we compared its gut bacteriomes with those of the domesticated mulberry silkworm, Bombyx mori L. Most abundant bacterial phyla identified in the gut of A. assamensis were Proteobacteria (78.1%), Bacteroidetes (8.0%) and Firmicutes (6.6%), whereas the most-abundant phyla in B. mori were Firmicutes (49-86%) and Actinobacteria (10-36%). Further, Gammaproteobacteria (57.1%), Alphaproteobacteria (10.47%) and Betaproteobacteria (8.28%) were the dominant bacterial classes found in the gut of A. assamensis. The predominant bacterial families in A. assamensis gut were Enterobacteriaceae (27.7%), Comamonadaceae (9.13%), Pseudomonadaceae (9.08%) Flavobacteriaceae (7.59%) Moraxellaceae (7.38%) Alteromonadaceae (6.8%) and Enterococcaceae (4.46%). In B. mori, the most-abundant bacterial families were Peptostreptococcaceae, Enterococcaceae, Lactobacillaceae and Bifidobacteriaceae, though all showed great variability among the samples. The core gut bacteriome of A. assamensis consisted of Pseudomonas, Acinetobacter, Variovorax, Myroides, Alteromonas, Enterobacter, Enterococcus, Sphingomonas, Brevundimonas, Oleispira, Comamonas, Oleibacter Vagococcus, Aminobacter, Marinobacter, Cupriavidus, Aeromonas, and Bacillus. Comparative gut bacteriome analysis revealed a more complex gut bacterial diversity in wild A. assamensis silkworms than in domesticated B. mori silkworms, which contained a relatively simple gut bacteriome as estimated by OTU richness. Predictive functional profiling of the gut bacteriome suggested that gut bacteria in A. assamensis were associated with a wide range of physiological, nutritional, and metabolic functions, including biodegradation of xenobiotics, lipid, amino acid, carbohydrate metabolism, and biosynthesis of secondary metabolites and amino acids. CONCLUSIONS: These results showed great differences in the composition and diversity of gut bacteria between the two silkworm species. Both insect species harbored core bacterial taxa commonly found in insects, but the relative abundance and composition of these taxa varied markedly.

Comparison of Echocardiography and Multi-Planar Gated Acquisition Scans for Predicting Cancer-Treatment-Related Cardiovascular Dysfunction.

BACKGROUND: Current guidelines recommend using sequential cardiac imaging to monitor for cancer treatment-related cardiac dysfunction (CTRCD) in patients undergoing potentially cardiotoxic chemotherapy. Multiple different imaging cardiac modalities are available and there are few prospective head-to-head comparative studies to help guide treatment. OBJECTIVES: To perform an exploratory prospective cohort study of "real-world" CTRCD comparing multigated acquisition nuclear ventriculography (MUGA) at the referring cancer specialist's discretion with a novel echocardiographic strategy at an Australian tertiary hospital. METHOD: Patients were recruited from haematology and oncology outpatient clinics if they were scheduled for treatment with anthracyclines and/or trastuzumab. Patients underwent simultaneous MUGA-based cardiac imaging (conventional strategy) at a frequency according to evidenced-based guidelines in addition to researcher-conducted echocardiographic imaging. The echocardiographic imaging was performed in all patients at time points recommended by international society guidelines. Outcomes included adherence to guideline recommendations, concordance between MUGA and echocardiographic left ventricular ejection fraction (LVEF) measurements, and detection of cardiac dysfunction (defined as >5% LVEF decrement from baseline by three-dimensional [3D]-LVEF). A secondary end point was accuracy of global longitudinal strain in predicting cardiac dysfunction. RESULTS: In total, 35 patients were recruited, including 15 with breast cancer, 19 with haematological malignancy, and one with gastric cancer. MUGA and echocardiographic LVEF measurements correlated poorly with limits of agreement of 30% between 3D-LVEF and MUGA-LVEF and 37% for 3D-LVEF and MUGA-LVEF. Only one case (2.9%) of CTRCD was diagnosed by MUGA, compared with 12 (34.2%) cases by echocardiography. Four (4) patients had >10% decrement in 3D-LVEF that was not detected by MUGA. Global longitudinal strain at 2 months displayed significant ability to predict CTRCD (area under the curve, 0.75, 95% confidence interval, 0.55-0.94). CONCLUSIONS: The MUGA correlates poorly with echocardiographic assessment with substantial discrepancy between MUGA and echocardiography in CTRCD diagnosis. Echocardiographic and MUGA imaging strategies should not be considered equivalent for imaging cancer patients, and a single imaging modality should ideally be used per patient to prevent misdiagnosis by inter-modality variation These findings should be considered hypothesis-generating and require confirmation with larger studies.

Homology modeling and molecular docking study of biogenic Muga silk nanoparticles as putative drug-binding system.

The recent emergence of natural biopolymers as drug delivery vehicles is attributed to their biodegradability and less systemic toxicity. Muga silk nanoparticles were prepared using microwave radiolysis method and were characterized by Fourier transform infrared spectroscopy, circular dichroism, X-ray diffraction and transmission electron microscopy. To find the applicability in the drug delivery system of these nanoparticle and to know the binding site(s), a computational study was carried out. The structure of the Muga protein is predicted using homology modeling, which is further used for molecular docking. The in silico molecular docking between the Muga silk nanoparticles and three United States Food and Drug Administration-approved model drugs of doxorubicin, remdesivir and dexamethasone was performed. The binding capabilities and binding energy of the Muga silk proteins with these drugs are determined. The basic idea of the active site and the residues involved in the binding of the drugs/ligands is also studied. Doxorubicin showed the highest binding affinity of -8.7 kcal/mol and that of the remdesivir and dexamethasone are found to be -7.2 and -7.9 kcal/mol, respectively. Such high binding affinity(ies) would help for slow drug release kinetics and the other two drugs can be loaded when the requirement is for sustained drug release. The data were also validated using the UV-vis. spectroscopy.

Spectroscopic analysis of Muga silk nanoparticles synthesized by microwave method.

Muga silk nanoparticles (MSNP) were synthesized using a microwave-assisted radiolysis method. The effect of microwave on the Muga protein secondary structures was analyzed. The evolution of the secondary structure from random coils to the ß-sheets was determined by using FTIR, circular dichroism and X-ray diffraction techniques. The results showed that Muga silk fibroin protein contained the primary structure in silk-I state. When the protein was irradiated with microwave, nanoparticle synthesis was possible having silk-II state imparting crystallinity. The silk nanoparticles were characterized by a particle size analyzer and found to be of ~240 nm in size. The optical properties of these nanoparticles were studied by UV-vis. spectroscopy and photoluminescence. For studying thermal properties, differential scanning calorimetry was performed that revealed early glass transition, which could be attributed to the presence of water and proteins. It also revealed that nanoparticles are thermally stable. Such studies are important for understanding more about the MSNP and would be beneficial for their further wide applications.

Nuclear Imaging for the Assessment of Cardiotoxicity from Chemotherapeutic Agents in Oncologic Disease.

PURPOSE OF REVIEW: In this review, we summarize the major known cardiac toxicities of common chemotherapeutic agents and the role of nuclear cardiac imaging for the surveillance and assessment of cancer therapeutics-related cardiac dysfunction in routine clinical practice. RECENT FINDINGS: Cardiotoxicity from chemotherapy causes a significant mortality and limits potentially life-saving treatment in cancer patients. Close monitoring of cardiac function during chemotherapy is an accepted method for reducing these adverse effects especially in patients with cancer therapeutics-related cardiac dysfunction. Nuclear imaging is a sensitive, specific, and highly reproducible modality for assessment of cardiac function. Nuclear imaging techniques including equilibrium radio nucleotide angiography, myocardial perfusion imaging, and novel experimental molecular imaging are the various objective tools available in addition to conventional echocardiography and cardiac magnetic resonance imaging in the surveillance, assessment, and follow-up of cancer therapeutics-related cardiac dysfunction.

Accuracy of left ventricular ejection fraction by contemporary multiple gated acquisition scanning in patients with cancer: comparison with cardiovascular magnetic resonance.

BACKGROUND: Multiple gated acquisition scanning (MUGA) is a common imaging modality for baseline and serial assessment of left ventricular ejection fraction (LVEF) for cardiotoxicity risk assessment prior to, surveillance during, and surveillance after administration of potentially cardiotoxic cancer treatment. The objective of this study was to compare the accuracy of left ventricular ejection fractions (LVEF) obtained by contemporary clinical multiple gated acquisition scans (MUGA) with reference LVEFs from cardiovascular magnetic resonance (CMR) in consecutive patients with cancer. METHODS: In a cross-sectional study, we compared MUGA clinical and CMR reference LVEFs in 75 patients with cancer who had both studies within 30 days. Misclassification was assessed using the two most common thresholds of LVEF used in cardiotoxicity clinical studies and practice: 50 and 55%. RESULTS: Compared to CMR reference LVEFs, MUGA clinical LVEFs were only lower by a mean of 1.5% (48.5% vs. 50.0%, p = 0.17). However, the limits of agreement between MUGA clinical and CMR reference LVEFs were wide at -19.4 to 16.5%. At LVEF thresholds of 50 and 55%, there was misclassification of 35 and 20% of cancer patients, respectively. CONCLUSIONS: MUGA clinical LVEFs are only modestly accurate when compared with CMR reference LVEFs. These data have significant implications on clinical research and patient care of a population with, or at risk for, cardiotoxicity.

Characterization and pathogenicity assessment of gut-associated microbes of muga silkworm Antheraea assamensis Helfer (Lepidoptera: Saturniidae).

Antheraea assamensis Helfer (muga silkworm) is an economically important endemic insect species of North Eastern Region of India. The silkworm is often susceptible to infection by pathogenic bacteria, leads to a disease commonly known as flacherie which causes 40% loss per annum to the silk industry. In this study, we have reported isolation, characterization and pathogenicity assessment of gut-associated bacteria of healthy and diseased muga silkworms. Thirty five bacterial isolates were screened from the gut of healthy and diseased silkworms by morphological observation and biochemical tests. 11 and 5 strains from healthy and diseased silkworm respectively were identified by 16S rRNA gene sequencing and analyzed. Pseudomonas aeruginosa (DRK1), Ornithinibacillus bavariensis (DRK2), Achromobacter xylosoxidans (KH3) and Staphylococcus aureus (FLG1) strains were commonly found in healthy as well as diseased larvae whereas, Bacillus thuringiensis (MK1) was found only in diseased larvae. Survivability analysis was performed with the identified strains by injection and oral administration (10(4)CFU/ml). The immune response of the silkworm against the pathogen was also studied by phenoloxidase and lysozyme enzyme activity assay, total and differential hemocyte count and phagocytic activity of hemocytes. It was observed that S. aureus, P. aeruginosa and B. thuringiensis significantly reduced the survivability of silkworm (p<0.001) hence found highly pathogenic. The lethal concentrations (LC50) values of the pathogenic strains were calculated at different time intervals (24, 48, 72 and 96h) within the range from 1.38×10(2) to 3.63×10(7)CFU/ml. The pathogenic groups demonstrated inhibition of phenoloxidase activity and decreased in total hemocyte count after 48h of infection. However, the lysozyme activity increased significantly in the pathogenic groups compared to the control (p<0.05). Granulocytes and plasmatocytes showed phagocytosis whereas; other types of cells did not show any phagocytic activity. Increasing granulocytes and plasmatocytes counts corroborates the results of phagocytic activity. The present study might be helpful in understanding the disease prognosis and colonization of bacteria causing the disease in muga silkworm.

Air pollution tolerance index of Persea bombycina: Primary food plant of endemic muga silkworm (Antheraeaassamensis).

Air pollution poses a significant threat to human health, ecosystems, and the livelihood of tribal communities. This study focuses on understanding the impact of air pollution on the primary food plant som (Persea bombycina Kost.) of the endemic Muga silkworm (Antheraea assamensis) and its implications for muga silk production. The study was conducted at two sites in northeastern India, one free from atmospheric pollutants (FAP) and the other affected by pollution from an oil refinery (PAS). Various atmospheric pollutants, including particulate matter, hydrocarbons, and heavy metals, were found to be higher at the PAS site. The study investigated biochemical parameters like ascorbic acid, relative water content, total chlorophyll, and extractable pH in the leaves of P. bombycina to determine its air pollution tolerance index (APTI). Results showed that the ascorbic acid content in the leaves increased significantly at the PAS site (p < 0.05), indicating the plant's adaptation to air pollution stress. Similarly, the APTI values were higher during summer compared to winter, suggesting better tolerance during the former season. Positive correlations were found between APTI and ascorbic acid content (p < 0.05), emphasizing the role of ascorbic acid as an antioxidant in mitigating the effects of air pollution. The study highlights the importance of understanding the tolerance levels of P. bombycina to develop protective measures for sustaining Muga silk production in the face of rapid industrialization and increasing pollution. This research can aid policymakers in balancing economic growth with environmental conservation and protecting traditional practices of tribal communities.

Imaging modality for left ventricular ejection fraction estimation and effect of implantable cardioverter-defibrillator on mortality in patients with heart failure.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) improve outcomes in patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≤35%. Less is known about whether outcomes varied between the 2 noninvasive imaging modalities used to estimate LVEF-2-dimensional echocardiography (2DE) and multigated acquisition radionuclide ventriculography (MUGA)-which use different principles (geometric vs count-based, respectively). OBJECTIVE: The purpose of this study was to examine whether the effect of ICD on mortality in patients with HF and LVEF ≤35% varied on the basis of LVEF measured by 2DE or MUGA. METHODS: Of the 2521 patients with HF with LVEF ≤35% in the Sudden Cardiac Death in Heart Failure Trial, 1676 (66%) were randomized to either placebo or ICD, of whom 1386 (83%) had LVEF measured by 2DE (n = 971) or MUGA (n = 415). Hazard ratios (HRs) and 97.5% confidence intervals (CIs) for mortality associated with ICD were estimated overall, checking for interaction, and within the 2 imaging subgroups. RESULTS: Of the 1386 patients in the present analysis, all-cause mortality occurred in 23.1% (160 of 692) and 29.7% (206 of 694) of patients randomized to ICD or placebo, respectively (HR 0.77; 97.5% CI 0.61-0.97), which is consistent with that in 1676 patients in the original report. HRs (97.5% CIs) for all-cause mortality in the 2DE and MUGA subgroups were 0.79 (0.60-1.04) and 0.72 (0.46-1.11), respectively (P = .693 for interaction). Similar associations were observed for cardiac and arrhythmic mortalities. CONCLUSION: We found no evidence that in patients with HF and LVEF ≤35%, the effect of ICD on mortality varied by the noninvasive imaging method used to measure LVEF.

Left ventricular ejection fraction by multigated acquisition scan using planar sodium iodide and cadmium-zinc-telluride cameras: a comparison with two-dimensional echocardiography.

Objectives: This study was undertaken to compare the correlation and agreement between Modified Simpson's method two-dimensional-echocardio-graphy (2D-echo) and rest multigated acquisition scan (MUGA) using both planar sodium iodide (pNaI) and cadmium-zinc-telluride (CZT) cameras to measure left ventricular ejection fraction (LVEF). Methods: One hundred and nine breast cancer patients monitored for cardiotoxicity underwent 2D-echo, followed by pNaI and CZT MUGA scans on the same day. LVEF for CZT camera was processed using both automatic and manual processing methods, thus yielding four methods for the LVEF analysis. Results: Significant correlation (p<0.01) was seen among all four methods, with varied correlation strengths. Moderate correlation was seen between 2D-echo and both pNaI (r=0.56) and CZT cameras (automatic r=0.54, manual r=0.56). Strong correlation was registered between pNaI and CZT camera (automatic r=0.72, manual r=0.71). Bland-Altman limits of agreement among the three scans were wide and suboptimal. The widest limits were -21.1 to +16.2 (37%) between 2D-echo and CZT auto-processing. Conclusion: Any one of the modalities can be used to measure LVEF, however, their results should not be used interchangeably. The same method of measurement is advised for serial scans.

Groundwater Potential Zone Mapping Using Analytical Hierarchy Process and GIS in Muga Watershed, Abay Basin, Ethiopia.

Groundwater is an important resource that contributes significantly to the total annual water supply. The purpose of the present study is to assess and delineate the groundwater recharge zone using geospatial technology through an analytical hierarchal process (AHP) method in to the Muga watershed, Abay Basin. Remote sensing satellite images and the corresponding data are used for the preparation of thematic layers, viz., geology, rainfall, slope, soil, curvature, topography wetness index, elevation, drainage density, land use land cover, and lineament density of the study watershed. All thematic layers are integrated with a multicriteria evaluation technique. Weighted overlay index analysis is carried out to give rank for each parameter. The weight is assigned for each thematic layer depending on the AHP technique. The reliability of the output is checked by the calculated consistency index and consistency ratio which is reasonably acceptable (0.044 < 0.1). Verification is done by considering the groundwater well locations in the validation datasets. The receiver operating characteristic curve and area under curve (=82.9%) are used to explore the prediction accuracy.

Multiple genome analytics framework: The case of all SARS-CoV-2 complete variants.

Pattern detection and string matching are fundamental problems in computer science and the accelerated expansion of bioinformatics and computational biology have made them a core topic for both disciplines. The requirement for computational tools for genomic analyses, such as sequence alignment, is very important, although, in most cases the resources and computational power required are enormous. The presented Multiple Genome Analytics Framework combines data structures and algorithms, specifically built for text mining and (repeated) pattern detection, that can help to efficiently address several computational biology and bioinformatics problems, concurrently, with minimal resources. A single execution of advanced algorithms, with space and time complexity O(nlogn), is enough to acquire knowledge on all repeated patterns that exist in multiple genome sequences and this information can be used as input by meta-algorithms for further meta-analyses. For the proof of concept and technology of the proposed Framework scalability, agility and efficiency, a publicly available dataset of more than 300,000 SARS-CoV-2 genome sequences from the National Center for Biotechnology Information has been used for the detection of all repeated patterns. These results have been used by newly introduced algorithms to provide answers to questions such as common patterns among all variants, sequence alignment, palindromes and tandem repeats detection, different organism genome comparisons, polymerase chain reaction primers detection, etc.

Deconstructing Ecosystem Service Conflicts through the Prisms of Political Ecology and Game Theory in a North-Western Mediterranean River Basin.

Power relationships, access and control, (in)equity, and (in)justice are key modulators of conflicts arising from ecosystem services between multiple stakeholders. A greater knowledge of stakeholder value systems and behaviors is crucial for understanding socioecological dynamics. We propose an analytical framework that combines political ecology and game theory to analyze water ecosystem services. This integrated framework was used to reinterpret concepts such as common goods, (a)symmetric flows, and (un)fair trade-offs in the context of ecosystem services. The purpose was to gain a better understanding of behaviors and (a)symmetries in power relationships between multiple stakeholders. We studied the case of a north-western Mediterranean river basin using data obtained from stakeholder interviews and newspaper articles. Our findings uncovered different types of stakeholder relationships, ranging from mutual support and cooperation to conflict. The proposed analytical framework shows how social mechanisms can affect ecosystem services flows, potentially facilitating or hindering the development of more equitable management models for natural resources. Supplementary Information: The online version contains supplementary material available at 10.1007/s10745-022-00325-5.

Secondary structural analysis of non-mulberry silk fibroin nanoparticles synthesized by using microwave and acetone method.

The 3D structure analysis for Muga silk protein was predicted through homology modeling and Ramachandran plot with the determination of quality index for Stereo/packing and 3D quality index. Silk Nanoparticles were synthesized using conventional desolvation and microwave-assisted radiolysis method from Muga silk fibroin. The secondary structure evolution due to two different synthesis methods was investigated using FTIR and Circular Dichroism (CD) spectroscopy. The microwave synthesized nanoparticles showed enhanced ß-sheet content than desolvation synthesized nanoparticles. The conformational changes of Muga silk fibroin protein to nanoparticle followed an ordered transition from random coil to α-helix then from α-helix to ß-turn and from ß-turn to ß-sheets where α-helix and ß-turn are the intermediate forms before getting stabilized to the metastable ß-sheets structure. The thermodynamics involved in secondary structure evolution was studied from CD analysis and activation energy involved in the formation of the secondary structure was determined. Communicated by Ramaswamy H. Sarma.

Impact of curative parathyroidectomy on left ventricular functions assessed with 2D ECHO and MUGA study.

Objectives: Primary hyperparathyroidism (PHPT) is associated with increased cardiovascular morbidity and mortality with inconsistent results on the reversibility of cardiovascular changes after parathyroidectomy (PTx). The present study was undertaken to evaluate both structural and functional cardiac changes and their reversal after PTx in patients with PHPT. Material and Methods: Thirty patients of symptomatic PHPT without cardiovascular risk factors were evaluated prospectively by means of 2D echocar- diography (ECHO) and Multigated Acquisition (MUGA) study before surgery and six months after curative parahyroidectomy. Results: Nine of 30 patients had hypertension which improved in two after PTx (p 0.20). Two patients had left ventricle hypertrophy on 2D ECHO pre- operatively which improved after PTx (p <0.001). Left ventricular ejection fraction (LVEF) did not show significant change before and after PTx on 2D ECHO. Nine out of 30 patients had hypertension which improved in two after PTx (p 0.20). Two patients with left ventricle hypertrophy on 2D ECHO preoperatively improved after PTx (p <0.001). Left ventricular ejection fraction (EF) did not depict significant change before and after PTx on 2D ECHO. Whereas, four out of six patients with preoperative EF <50% representing systolic dysfunction on MUGA study showed improvement after PTx. On 2D ECHO, eight patients depicted diastolic dysfunction which improved in six patients after curative surgery (p= 0.07). However, on MUGA study, 13 pa- tients presented with tTPF >180 ms indicating diastolic dysfunction, of which ten showed improvement after PTx (p= 0.007). Conclusion: The present study analyzed preoperative and postoperative cardiac function using both 2D ECHO and MUGA study. MUGA study provided a more objective assessment of the cardiac function by determining left ventricular ejection fraction and diastolic dysfunction.

Assessment of left ventricular function by CMR versus MUGA scans in breast cancer patients receiving trastuzumab: a prospective observational study.

Little is known about the comparison of multiple-gated acquisition (MUGA) scanning with cardiovascular magnetic resonance (CMR) for serial monitoring of HER2+ breast cancer patients receiving trastuzumab. The association of cardiac biomarkers with CMR left ventricular (LV) function and volume is also not well studied. Our objectives were to compare CMR and MUGA for left ventricular ejection fraction (LVEF) assessment, and to examine the association between changes in brain natriuretic peptide (NT-BNP) and troponin-I and changes in CMR LV function and volume. This prospective longitudinal two-centre cohort study recruited HER2+ breast cancer patients between January 2010 and December 2013. MUGA, CMR, NT-BNP and troponin-I were performed at baseline, 6, 12, and 18 months after trastuzumab initiation. In total, 41 patients (age 51.7 ± 10.8 years) were enrolled. LVEF comparison between MUGA and CMR demonstrated weak agreement (Lin's correlation coefficient r = 0.46, baseline; r = 0.29, 6 months; r = 0.42, 12 months; r = 0.39, 18 months; all p < 0.05). Bland-Altman plots demonstrated wide LVEF agreement limits (pooled agreement limits 3.0 ± 6.2). Both modalities demonstrated significant LVEF decline at 6 and 12 months from baseline, concomitant with increased LV volumes on CMR. Changes in NT-BNP correlated with changes in LV diastolic volume at 12 and 18 months (p < 0.05), and LV systolic volume at 18 months (p < 0.05). Changes in troponin-I did not correlate with changes in LV function or volume at any timepoint. In conclusion, CMR and MUGA LVEF are not interchangeable, warranting selection and utility of one modality for serial monitoring. CMR is useful due to less radiation exposure and accuracy of LV volume measurements. Changes in NT-BNP correlated with changes in LV volumes.

Silk Fibroin Scaffold-Based 3D Co-Culture Model for Modulation of Chondrogenesis without Hypertrophy via Reciprocal Cross-talk and Paracrine Signaling.

In this study, the effect of cellular cross-talk on modulation of chondrogenesis and hypertrophy while minimizing the usage of articular chondrocytes (ACs) has been investigated. Herein, co-culture of ACs with adipose-derived human mesenchymal stem cells (ADhMSCs) was employed for cross-talk within silk fibroin (SF)-based three-dimensional (3D) scaffolds. The co-culture model was developed by co-culturing four different ratios of ADhMSCs to ACs: 1:0, 3:1, 1:1, and 0:1 on porous 3D SF scaffolds for 21 days. The co-culture groups were cultured in defined media without adding any exogenous growth factors except the monoculture group, ADhMSC-only controls. The co-cultured constructs indicated significantly higher cellular viability and proliferation than the control monoculture groups. The supernatants of co-culture groups indicated significantly higher levels of TGF-ß1 and IL-10, which confirmed the production of the morphogens/signaling molecules by chondrocytes for induction of ADhMSCs differentiation toward the chondrogenic phenotype. Biochemical assays indicated enhanced accumulation of sulfated glycosaminoglycans, collagen, and high DNA content along with high cellularity in co-culture groups than chondrocyte-only controls. Co-culture groups revealed synergistic interactions between cells as indicated by the interaction index value ranging from 2-3. Furthermore, upregulation of putative chondrogenic markers-aggrecan, sox-9, and collagen II, and significantly reduced expression of hypertrophic genes-collagen type X and MMP-13 was revealed in co-culture constructs. Histological and immunohistochemical staining also demonstrated even distribution and deposition of ECM in co-cultured constructs. Taken together, this work presents the potential of the developed 3D co-culture model toward modulation of chondrogenesis and hypertrophy via 3D microenvironment induced by physicochemical and biological properties of SF scaffolds, synergistic interactions between cells, and paracrine signaling in the co-culture system.

Utility of Left Ventricular Ejection Fraction Measurements Before the Administration of Doxorubicin-Based Chemotherapy in Patients With Diffuse Large B-Cell Lymphoma.

OBJECTIVE: To determine the utility of routine measurements of left ventricular ejection fraction (LVEF) before the administration of doxorubicin-based chemotherapy (DOX) in patients with diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: We investigated the frequency of LVEF measurements before the initiation of therapy in 291 patients with DLBCL at our institution from January 1, 2001, through December 31, 2013, and reviewed whether LVEF varied in patients with an underlying risk of cardiac disease (CD), the relationship between LVEF and subsequent DLBCL treatment, and congestive heart failure (CHF) occurrence in DOX-treated patients. RESULTS: Left ventricular ejection fraction was measured in 258 patients before the administration of chemotherapy and was not associated with underlying CHF risk (P=.94). Left ventricular ejection fraction was normal in 243 patients (94%) and low in 15 patients. Doxorubicin-based chemotherapy was administered to 206 patients with normal LVEF (85%) vs 8 patients with low LVEF (53%) (P=.006). However, when previous CD was factored out, LVEF did not influence subsequent treatment decisions (P=.51). Congestive heart failure occurred in 18 patients, and the risk was similar in patients treated with and without DOX. For all patients who had LVEF measured, CHF incidence did not differ between patients who received DOX and those who did not (P>.99). Moreover, there was no difference in CHF incidence after receiving DOX between those who had normal and low LVEF results (P=.45). CONCLUSION: The decision to administer DOX was influenced by LVEF status only when previous CD was factored out. Furthermore, CHF incidence posttreatment did not differ between patients who did and did not receive DOX. These preliminary findings challenge the practice of performing cardiac screening before DOX for patients with DLBCL.

Dextrose modified flexible tasar and muga fibroin films for wound healing applications.

This paper is focused on preparation and characterization of regenerated muga and tasar fibroin flexible films from cocoon using ionic liquid. These flexible muga and tasar fibroin films were prepared by incorporating dextrose (5 to 15% w/w) as plasticizer. The mechanical, thermal, physical, morphological and biological properties of dextrose plasticized muga and tasar fibroin films were characterized. These plasticized films showed higher elongation at break as well as water holding capacity as compared to the un-plasticized films. The surface roughness and water absorbance capacity of the dextrose plasticized films were higher than un-plasticized films, which results in improved adherence and proliferation of L929 fibroblast cells. Gentamicin loaded plasticized muga and tasar fibroin films showed slightly higher rate of release as compared to un-plasticized films. The biodegradability of dextrose plasticized films was significantly higher as compared to their respective counterpart. The regeneration of flexible muga and tasar silk fibroin films pave the way to expand potential use of non-mulberry in the field of biomedical such as wound dressing.

Clinical outcomes meta-analysis: measuring subendocardial perfusion and efficacy of transmyocardial laser revascularization with nuclear imaging.

INTRODUCTION: Randomized and nonrandomized clinical trials have tried to assess whether or not TMR patients experience an increase in myocardial perfusion. However there have been inconsistencies reported in the literature due to the use of different nuclear imaging modalities to test this metric. The primary purpose of this meta-analysis was to determine whether SPECT, MUGA and PET scans demonstrate changes in myocardial perfusion between lased and non-lased subjects and whether laser type affects myocardial perfusion. The secondary purpose was to examine the overall effect of laser therapy on clinical outcomes including survival, hospital re-admission and angina reduction. METHODS: Sixteen studies were included in the primary endpoint analysis after excluding all other non-imaging TMR papers. Standardized mean difference was used as the effect size for all quantitative outcomes and log odds ratio was used as the effect size for all binary outcomes. RESULTS: Statistically significant improvements in myocardial perfusion were observed between control and treatment groups in myocardial perfusion at 6-month follow up using PET imaging with a porcine model. However non-significant differences were observed in patients at 3 and 12 months using SPECT, PET or MUGA scans. Both CO2 and Ho:YAG laser systems demonstrated an increase in myocardial perfusion however this effect was not statistically significant. In addition both laser types displayed statistically significant decreases in patient angina at 3, 6 and 12 months but non-significant increases in survival rates and decreases in hospital re-admissions. CONCLUSION: In order to properly assess myocardial perfusion in TMR subjects, subendocardial perfusion needs to be analyzed via nuclear imaging. PET scans can provide this level of sensitivity and should be utilized in future studies to monitor and detect perfusion changes in lased and non-lased subjects.