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Surgical site infections (SSI) can represent a major complication of pancreaticoduodenectomy (PD). We summarize the outcomes of process improvement efforts to reduce the SSI rates in PD that includes replacing Cefazolin with Ceftriaxone-Metronidazole as antibiotic prophylaxis. Additional efforts included current assessment of biliary microbiome and potential prophylactic failures based on bile cultures and suspected antibiotic allergies.A single-center review of PD patients from January-2012 to March-2021. Study groups were divided into Pre and Post May-2015 (Group 1 and 2, respectively) when Ceftriaxone-Metronidazole prophylaxis and routine intraoperative cultures were standardized. Univariate and multivariable analyses were conducted to assess groups' differences and association with SSI.Six hundred ninety patients identified [267(38.7%) and 423(61.3%) in Group 1 and Group2, respectively]. After antibiotic change, SSI rates decreased from 28.1% to 16.5% (incisional: 17.6%-7.5%, organ-space or abscess: 17.2%-13.0%), Group 1 and Group 2, respectively, P0.001. Ceftriaxone-Metronidazole was used in 75.9% of patients Group 2. When adjusting for other covariates, an SSI-decrease was associated only with Ceftriaxone-Metronidazole (OR 0.34, P0.001).Ongoing process improvement has resulted in decreased SSIs with Ceftriaxone-Metronidazole prophylaxis. The benefit of Ceftriaxone-Metronidazole is independent of the biliary microbiome. Improving prophylaxis for those with suspected penicillin allergy is warranted.

Valvular endothelial cells line the outer layer of heart valves and can withstand shear forces caused by blood flow. In contrast to vascular endothelial cells, there is limited amount of research over valvular endothelial cells. For this reason, the exact physiologic behavior of valvular endothelial cells is unclear. Prior studies have concluded that valvular endothelial cells align perpendicularly to the direction of blood flow, while vascular endothelial cells align parallel to blood flow. Other studies have suggested that different ranges of shear stress uniquely impact the behavior of valvular endothelial cells. The goal of this study was to characterize the response of valvular endothelial cell under different types, magnitudes, and durations of shear stress. In this work, the results demonstrated that with increased shear rate and duration of exposure, valvular endothelial cells no longer possessed the traditional cuboidal morphology. Instead through the change in cell circularity and aspect ratio, valvular endothelial cells aligned in an organized manner. In addition, different forms of shear exposure caused the area and circularity of valvular endothelial cells to decrease while inducing mesenchymal transformation validated through αSMA and TGFβ1 expression. This is the first investigation showing that valvular endothelial cells alignment is not as straightforward as once thought (perpendicular to flow). Different types and magnitudes of shear induce different local behaviors. This is also the first demonstration of valvular endothelial cells undergoing EndMT without chemical inducers on a soft surface in vitro. Findings from this study provide insights to understanding the pathophysiology of valvular endothelial cells which can potentially propel future artificial engineered heart valves.

Acute respiratory distress syndrome (ARDS) is a life-threatening form of acute lung injury (ALI) associated with hypoxemic lung damage and inflammation. Matrix metalloproteinase protein-3 (MMP3 or Stromelysin-1) is known to promote vascular injury in ALI/ARDS. Cisatracurium, a nicotinic neuromuscular blocker, is used in ARDS patients to decrease mechanical ventilator dyssynchrony, increase oxygenation, and improve mortality. However, the magnitude and the underlying mechanisms of these potential benefits of cisatracurium remains unclear. We investigated the effect of cisatracurium on lipopolysaccharide-induced MMP3 expression in human microvascular endothelial cells. In our results, cisatracurium treatment significantly decreased LPS-induced MMP3 expression and increased expression of cell junction proteins such as vascular endothelial cadherin (VE-cadherin) and claudin-5.

The severe acute respiratory syndrome coronavirus 2 that causes coronavirus disease 2019 (COVID‐19) binds to the angiotensin‐converting enzyme 2 (ACE2) to gain cellular entry. Akt inhibitor triciribine (TCBN) has demonstrated promising results in promoting recovery from advanced‐stage acute lung injury in preclinical studies. In the current study, we tested the direct effect of TCBN on ACE2 expression in human bronchial (H441) and lung alveolar (A549) epithelial cells. Treatment with TCBN resulted in the downregulation of both messenger RNA and protein levels of ACE2 in A549 cells. Since HMGB1 plays a vital role in the inflammatory response in COVID‐19, and because hyperglycemia has been linked to increased COVID‐19 infections, we determined if HMGB1 and hyperglycemia have any effect on ACE2 expression in lung epithelial cells and whether TCBN has any effect on reversing HMGB1‐ and hyperglycemia‐induced ACE2 expression. We observed increased ACE2 expression with both HMGB1 and hyperglycemia treatment in A549 as well as H441 cells, which were blunted by TCBN treatment. Our findings from this study, combined with our previous reports on the potential benefits of TCBN in the treatment of acute lung injury, generate reasonable optimism on the potential utility of TCBN in the therapeutic management of patients with COVID‐19., Inflammatory stimuli by HMGB1 and hyperglycemia elevated angiotensin‐converting enzyme 2 (ACE2) expression in human bronchial and alveolar epithelial cells, which was blunted by treatment with triciribine, a tricyclic adenosine analog, and an Akt pathway inhibitor. The effect of triciribine on ACE2 expression appeared to be independent of Akt activity modulation. Our study suggests the potential utility of triciribine in the therapeutic management of patients with coronavirus disease 2019.

Endothelial-to-mesenchymal transition (EndMT) and fibroblast-to-myofibroblast (FibroMF) differentiation are frequently reported in organ fibrosis. Stromelysin1, a matrix metalloprotease-3 (MMP3) has been indicated in vascular pathologies and organ injuries that often lead to fibrosis. In the current study, we investigated the role of stromelysin1 in EndMT and FibroMF differentiation, which is currently unknown. In our results, whereas TGFβ2 treatment of endothelial cells (ECs) induced EndMT associated with increased expression of stromelysin1 and mesenchymal markers such as α-smooth muscle actin (αSMA), N-cadherin, and activin linked kinase-5 (ALK5), inhibition of stromelysin1 blunted TGFβ2-induced EndMT. In contrast, treatment of NIH-3T3 fibroblasts with TGFβ1 promoted FibroMF differentiation accompanied by increased expression of αSMA, N-cadherin, and ALK5. Intriguingly, stromelysin1 inhibition in TGFβ1-stimulated myofibroblasts further exacerbated fibroproliferation with increased FibroMF marker expression. Gene Expression Omnibus (GEO) data analysis indicated increased stromelysin1 expression associated with EndMT and decreased stromelysin1 expression in human pulmonary fibrosis fibroblasts. In conclusion, our study has identified that EndMT and FibroMF differentiation are reciprocally regulated by stromelysin1.

The multi-gene claudin (CLDN) family of tight junction proteins have isoform-specific roles in blood–tissue barrier regulation. CLDN17, a putative anion pore-forming CLDN based on its structural characterization, is assumed to regulate anion balance across the blood-tissue barriers. However, our knowledge about CLDN17 in physiology and pathology is limited. The current study investigated how Cldn17 deficiency in mice affects blood electrolytes and kidney structure. Cldn17−/− mice revealed no breeding abnormalities, but the newborn pups exhibited delayed growth. Adult Cldn17−/− mice displayed electrolyte imbalance, oxidative stress, and injury to the kidneys. Ingenuity pathway analysis followed by RNA-sequencing revealed hyperactivation of signaling pathways and downregulation of SOD1 expression in kidneys associated with inflammation and reactive oxygen species generation, demonstrating the importance of Cldn17 in the maintenance of electrolytes and reactive oxygen species across the blood-tissue barrier.

The adaptive immune response could play a major role in the resolution of lung injury. Although regulatory T cells (Tregs) have been implicated in promoting the resolution of lung injury, therapeutic strategies to enhance Treg quantity and activity at the site of injury need further exploration. In the current study, Akt inhibition using triciribine (TCBN), given 48 h after lipopolysaccharide (LPS) administration, increased Tregs-promoted resolution of acute lung injury (ALI). TCBN treatment enhanced the resolution of LPS-induced ALI on day 7 by reducing pulmonary edema and neutrophil activity associated with an increased number of CD4+/FoxP3+/CD103+ and CTLA4+ effector Tregs, specifically in the injured lungs and not in the spleen. Treatment of EL-4 T-lymphocytes with two Akt inhibitors (TCBN and MK-2206) for 72 h resulted in increased FoxP3 expression in vitro. On the other end, Treg-specific PTEN knockout (PTENTreg KO) mice that have a higher Akt activity in its Tregs exhibited a significant impairment in ALI resolution, increased edema, and neutrophil activity associated with a reduced number of CD4+/FoxP3+/CD103+ and CTLA4+ effector Tregs as compared with the control group. In conclusion, our study identifies a potential target for the treatment of late-stage ALI by promoting resolution through effector Treg-mediated suppression of inflammation.

Cell junctions maintain the blood-tissue barriers to preserve vascular and tissue integrity. Viral infections reportedly modulate cell–cell junctions to facilitate their invasion. However, information on the effect of COVID-19 infection on the gene expression of cell junction and cytoskeletal proteins is limited. Using the Gene Expression Omnibus and Reactome databases, we analyzed the data on human lung A549, NHBE, and Calu-3 cells for the expression changes in cell junction and cytoskeletal proteins by SARS-CoV-2 (CoV-2) infection. The analysis revealed changes in 3,660 genes in A549, 100 genes in NHBE, and 592 genes in Calu-3 cells with CoV-2 infection. Interestingly, EGOT (9.8-, 3- and 8.3-fold; p

Several studies have unraveled the negative role of Akt1 in advanced cancers, including metastatic prostate cancer (mPCa). Hence, understanding the consequences of targeting Akt1 in the mPCa and identifying its downstream novel targets is essential. We studied how Akt1 deletion in PC3 and DU145 cells activates the Nodal pathway and promotes PCa epithelial-to-mesenchymal transition (EMT) and metastasis. Here we show that Akt1 loss increases Nodal expression in PCa cells accompanied by activation of FoxO1/3a, and EMT markers Snail and N-cadherin as well as loss of epithelial marker E-cadherin. Treatment of PCa cells with FoxO inhibitor AS1842856 abrogated the Nodal expression in Akt1 deleted PCa cells. Akt1 deficient PCa cells exhibited enhanced cell migration and invasion in vitro and lung metastasis in vivo, which were attenuated by treatment with Nodal pathway inhibitor SB505124. Interestingly, Nodal mRNA analysis from two genomic studies in cBioportal showed a positive correlation between Nodal expression and Gleason score indicating the positive role of Nodal in human mPCa. Collectively, our data demonstrate Akt1-FoxO-Nodal pathway as an important mediator of PCa metastasis and present Nodal as a potential target to treat mPCa patients.

Both aortic and mitral valves calcify in pathological conditions; however, the prevalence of aortic valve calcification is high whereas mitral valve leaflet calcification is somewhat rare. Patterns of valvular calcification may differ due to valvular architecture, but little is known to that effect. In this study, we investigated the intrinsic osteogenic differentiation potential of aortic versus mitral valve interstitial cells provided minimal differentiation conditions. For the assessment of calcification at the cellular level, we used classic inducers of osteogenesis in stem cells: β-glycerophosphate (β-Gly), dexamethasone (Dex), and ascorbate (Asc). In addition to proteomic analyses, osteogenic markers and calcium precipitates were evaluated across treatments of aortic and mitral valve cells. The combination of β-Gly, Asc, and Dex induced aortic valve interstitial cells to synthesize extracellular matrix, overexpress osteoblastic markers, and deposit calcium. However, no strong evidence showed the calcification of mitral valve interstitial cells. Mitral cells mainly responded to Asc and Dex by cell activation. These findings provide a deeper understanding of the physiological properties of aortic and mitral valves and tendencies for calcific changes within each valve type, contributing to the development of future therapeutics for heart valve diseases.

Heart valves reside in a dynamic mechanical environment experiencing a multitude of forces. These forces have been shown to play a key role in valvular pathophysiology. However, knowledge of proteins involved in valvular mechanobiology is limited to only a few proteins of interest, namely, α-smooth muscle actin, transforming growth factor β, etc. Valvular endothelium mediates valvular homeostasis and controls valvular interstitial cell phenotype transformation. But, how endothelium mediates valvular response to dynamic forces is also unknown. In this study, proteomic analysis of mitral valve anterior leaflets under 10% cyclic radial strain was performed. Endothelium from these samples was removed to test how endothelium mediates mitral valve response to stretch. Results show that stretch downregulated cytoskeletal proteins and proteins involved in energy metabolism such as glycolysis and oxireductase activity. Endothelium removal resulted in downregulation of extracellular matrix and cell-matrix adhesion proteins. Removal of endothelium also resulted in upregulation of translation-related and chaperone proteins. Overall, this high throughput study provides insights into new protein groups that may be involved in mitral valve response to mechanical stretch and loss of endothelium. Impact statement This work is important to the field of heart valve pathophysiology as it provides new insights into molecular markers of mechanically induced valvular degeneration as well as the protective role of the valvular endothelium. These discoveries reported here advance our current knowledge of the valvular endothelium and how its removal essentially takes valve leaflets into an environmental shock. In addition, it shows that static conditions represent a mild pathological state for valve leaflets, while 10% cyclic stretch provides valvular cell quiescence. These findings impact the field by informing disease stages and by providing potential new drug targets to reverse or slow down valvular change before it affects cardiac function.

Despite the availability of effective antifungal therapy, cryptococcal meningoencephalitis (CM) remains associated with elevated mortality. The spectrum of symptoms associated with the central nervous system (CNS) cryptococcosis is directly caused by the high fungal burden in the subarachnoid space and the peri-endothelial space of the CNS vasculature, which results in intracranial hypertension (ICH). Management of intracranial pressure (ICP) through aggressive drainage of cerebrospinal fluid by lumbar puncture is associated with increased survival. Unfortunately, these procedures are invasive and require specialized skills and supplies that are not readily available in resource-limited settings that carry the highest burden of CM. The institution of pharmacologic therapies to reduce the production or increase the resorption of cerebrospinal fluid would likely improve clinical outcomes associated with ICH in patients with CM. Here, we discuss the potential role of multiple pharmacologic drug classes such as diuretics, corticosteroids, and antiepileptic agents used to decrease ICP in various neurological conditions as potential future therapies for CM.

Epidermal growth factor receptor tyrosine kinase (EGFR-TK) is one of the key regulators that exhibit pivotal role in proliferation of cancer cell. Quinazolinones are studiedly widely as effective EGFR-TK inhibitor because of their higher affinity to bind with adenosine triphosphate (ATP) binding site of receptor tyrosine kinases. However, their toxicity due to non-specific binding to tyrosine kinase in non-cancerous normally dividing cells of the body limits its applicability as a cancer therapeutics. In the present investigation a series of thirty-four novel synthesized thiazolo- [2, 3-b] quinazolinones were studied in silico as EGFR-TK inhibitors. All the thirty-four compounds were screened against EGFR-TK domain using multiple software’s (AutoDock Vina, Argus Lab, YASARA, and MOE). The interactions of the ligands with amino acid residues, namely, Lys721, Met769 and Asp831 of the active site were through the functional groups on aryl substituents at position 3 and 5 of the thiazolo- [2, 3-b] quinazolinone scaffold. The methyl substituents at position 8 of the ligands had prominent hydrophobic interactions in the active site cavity of EGFR-TK domain. The compounds 5ab, 5aq, and 5bq were predicted to be non-toxic and drug-like by in silico ADMET investigations. These compounds were considered for further investigation due to their non-toxicity and higher docking score ranking in different docking methods. The molecular dynamics (MD) simulation for 100 ns of docked complexes revealed the stability of these compounds. The binding free energy determined using Molecular Mechanics Generalized Born Model and Solvent Accessibility (MM-GBSA) method indicate that thiazolo- [2, 3-b] quinazolinone has high inhibitory efficacy similar to the standard drug, erlotinib (5ab - 22.45, 5aq -22.23, 5bq -20.76, and erlotinib -24.11 kcal/mol). In silico studies and MD simulations indicated that compounds (5ab, 5aq and 5bq) could be potential EGFR-TK inhibitors and require further validation as cancer therapeutics using carcinoma cell lines.

Epithelial and endothelial cell-cell contacts are established and maintained by several intercellular junctional complexes. These structurally and biochemically differentiated regions on the plasma membrane primarily include tight junctions (TJs), and anchoring junctions. While the adherens junctions (AJs) provide essential adhesive and mechanical properties, TJs hold the cells together and form a near leak-proof intercellular seal by the fusion of adjacent cell membranes. AJs and TJs play essential roles in vascular permeability. Considering their involvement in several key cellular functions such as barrier formation, proliferation, migration, survival, and differentiation, further research is warranted on the composition and signaling pathways regulating cell-cell junctions to develop novel therapeutics for diseases such as organ injuries. The current review article presents our current state of knowledge on various cell-cell junctions, their molecular composition, and mechanisms regulating their expression and function in endothelial and epithelial cells.

In the ongoing coronavirus diseases-2019 (COVID-19) crisis that caused immense suffering and deaths, the choice of therapy for the prevention and life-saving conditions must be based on sound scientific evidence. Uncertainty and apprehension are exacerbated in people using angiotensin-converting enzyme (ACE) inhibitors to control their comorbidities such as hypertension and diabetes. These drugs are reported to result in unfavorable outcome as they tend to increase the levels of ACE2 which mediates the entry of SARS-CoV-2. Amiloride, a prototypic inhibitor of epithelial sodium channels (ENaC) can be an ideal candidate for COVID-19 patients, given its ACE reducing and cytosolic pH increasing effects. Moreover, its potassium-sparing and anti-epileptic activities make it a promising alternative or a combinatorial agent.

Whereas physiological vascular permeability (VP) mediates selective transport of plasma, electrolytes, proteins, and cells across an intact endothelial barrier, pathological VP results in the loss of endothelial barrier integrity. Whereas physiological VP is a feature of regular host defense and tissue repair, compromised barrier function may lead to aberrant vascular leakage, concurrent tissue edema, and inflammation eventually causing life-threatening conditions such as acute lung injury or acute respiratory distress syndrome, cancer, kidney injury, etc. Measurement of VP helps to identify, design, and optimize anti-leak therapies. Further, it can define the effect of a stimulus or a gene modulation in endothelial-barrier regulation. The degree of VP can be of importance to determine the stage of cancer and disease prognosis. This chapter discusses Miles assay, which is a well-established, relatively simple, and a reliable in vivo technique to assess VP as a surrogate measurement. Although a reliable technique, Miles assay is time-consuming, and the technique does not consider the compounding factors that may increase VP independently of endothelial-barrier regulation, such as blood pressure or blood flow. As an alternative, we describe fluorescein isothiocyanate-dextran lung permeability assay, a method that can also be adapted to measure VP and edema in other organs such as the brain and kidney.

Fibroblast-to-myofibroblast (FibroMF) differentiation is crucial for embryogenesis and organ fibrosis. Although transforming growth factor-β (TGFβ) is the primary mediator of FibroMF differentiation, the type-I receptor (TGFβRI) responsible for this has not yet been confirmed. In the current study, we investigated the ALK1 and ALK5 expressions in TGFβ1-stimulated NIH 3T3 fibroblasts to compare with the data from the Gene Expression Omnibus (GEO) repository. In our results, whereas TGFβ1 treatment promoted FibroMF differentiation accompanied by increased ALK5 expression and reduced ALK1 expression, TGFβ1-induced FibroMF differentiation and increased α-smooth muscle actin (αSMA) and ALK5 expression were inhibited by co-treatment with ALK5 inhibitor SB431542. GEO database analysis indicated increased ALK5 expression and reduced ALK1 expression in fibrotic compared to normal mouse or human tissues correlating with organ fibrosis progression. Finally, the inhibitors of Akt, mTOR, and β-catenin suppressed TGFβ1-induced ALK5 expression, indicating that the Akt pathway promotes FibroMF differentiation via ALK5 expression and fibrosis.

The endothelium is a thin layer of squamous cells that acts as a semipermeable barrier regulating vascular permeability to let molecules pass through it thereby maintaining tissue fluid homeostasis. Physiological increase in endothelial or vascular permeability is transient, transpired by post-tissue injury during the initial phases of healing, whereas pathological permeability is persistent commonly witnessed in conditions such as atherosclerosis, chronic inflammation, tumor growth, and diabetic retinopathy. The in vivo or in situ use of animal models in the assessment of permeability not only raises inevitable ethical concerns but also confers difficulty to apply to high-throughput screening. Therefore, there is an ever-increasing dependency on in vitro studies to assess drug permeability, and various research programs have suffered to develop appropriate in vitro assays for measurement and prediction. In vitro models that both mimic in vivo microvascular endothelium and can be utilized to record changes in endothelial permeability are vital in delineating the mechanisms involved in the prevention and treatment of disorders related to vascular permeability. The Transwell

Background Medication errors may account up to one-third of all medical errors in hospitals, thereby leading to adverse outcomes such as higher mortality rate and longer hospital stay. Objectives The primary objective of the study was to determine whether patient safety can be improved by clinical pharmacy services. The study also aimed to reveal whether medication errors can be prevented by any means. Methods A prospective, observational study was conducted in a multispecialty hospital in India. Prescription audit was performed for patients followed by necessary intervention by the concerned physician. Chi-squared test, paired t-test and ANOVA were performed to test statistical significance. Results A total of 699 errors were encountered by 501 of 1149 patients enrolled. Prescription errors accounted for the majority (87.1%) of errors followed by administration (7.4%), transcription (4.3%) and dispensing (1.2%) errors. Average error per patient showed a significant gradual decline from baseline (2.08) to the final follow-up (1.06). ICU patients encountered a higher rate (52.8%) of errors than general ward group (42.8%), while geriatric population witnessed a low error rate (18.8%) compared to adults (72%). Conclusions The study was not only successful in highlighting the impact of medication error assessment on patient safety, but it also demonstrated that medication errors can be lowered with the help of clinical pharmacy services. Findings from the study conclude that medication errors can be prevented if healthcare professionals are educated appropriately to avoid recurrence of past mistakes.

Whereas physiological vascular permeability (VP) mediates selective transport of plasma, electrolytes, proteins, and cells across an intact endothelial barrier, pathological VP results in the loss of endothelial barrier integrity. Whereas physiological VP is a feature of regular host defense and tissue repair, compromised barrier function may lead to aberrant vascular leakage, concurrent tissue edema, and inflammation eventually causing life-threatening conditions such as acute lung injury or acute respiratory distress syndrome, cancer, kidney injury, etc. Measurement of VP helps to identify, design, and optimize anti-leak therapies. Further, it can define the effect of a stimulus or a gene modulation in endothelial-barrier regulation. The degree of VP can be of importance to determine the stage of cancer and disease prognosis. This chapter discusses Miles assay, which is a well-established, relatively simple, and a reliable in vivo technique to assess VP as a surrogate measurement. Although a reliable technique, Miles assay is time-consuming, and the technique does not consider the compounding factors that may increase VP independently of endothelial-barrier regulation, such as blood pressure or blood flow. As an alternative, we describe fluorescein isothiocyanate-dextran lung permeability assay, a method that can also be adapted to measure VP and edema in other organs such as the brain and kidney.

The endothelium is a thin layer of squamous cells that acts as a semipermeable barrier regulating vascular permeability to let molecules pass through it thereby maintaining tissue fluid homeostasis. Physiological increase in endothelial or vascular permeability is transient, transpired by post-tissue injury during the initial phases of healing, whereas pathological permeability is persistent commonly witnessed in conditions such as atherosclerosis, chronic inflammation, tumor growth, and diabetic retinopathy. The in vivo or in situ use of animal models in the assessment of permeability not only raises inevitable ethical concerns but also confers difficulty to apply to high-throughput screening. Therefore, there is an ever-increasing dependency on in vitro studies to assess drug permeability, and various research programs have suffered to develop appropriate in vitro assays for measurement and prediction. In vitro models that both mimic in vivo microvascular endothelium and can be utilized to record changes in endothelial permeability are vital in delineating the mechanisms involved in the prevention and treatment of disorders related to vascular permeability. The Transwell® and the electric cell-substrate impedance sensing (ECIS) assays are extensively used to assess the trans-endothelial permeability of solutes such as albumin, dextrans, and sucrose across endothelial monolayers and based on electrical resistance, etc. These models have several advantages such as the ease to perform and avoid the complexities of using a live animal.

Valvular interstitial cells (VICs) constitute the major cell population in heart valves. Quiescent fibroblastic VICs are seen in adult healthy valves. They become activated myofibroblastic VICs during development, in diseased valves and in vitro . 2D substrate stiffness within a 5–15 kPa range along with high passage numbers promote VIC activation in vitro . In this study, we characterize VIC quiescence and activation across a 1–21 kPa range of substrate stiffness and passages. We define a cell morphology characterization system for VICs as they transform. We hypothesize that VICs show distinct morphological characteristics in different activation states and the morphology distribution varies with substrate stiffness and passage number. Four VIC morphologies - tailed, spindle, rhomboid and triangle - account for the majority of VIC in this study. Using α-smooth muscle actin (α-SMA), non-muscle myosin heavy chain B (SMemb) and transforming growth factor β (TGF-β) as activation markers for validation, we developed a system where we categorize morphology distribution of VIC cultures, to be potentially used as a non-destructive detection method of activation state. We also show that this system can be used to force stiffness-induced deactivation. The reversibility in VIC activation has important implications in in vitro research and tissue engineering.

Advanced Air Mobility (AAM) is an emerging transportation system that will enable the safe and efficient low altitude operations and applications of unmanned aircraft (e.g., passenger transportation and cargo delivery) in the national airspace. This system is currently under active research and development by NASA in collaboration with FAA, other federal partner agencies, industry, and academia to develop its infrastructure, information architecture, software functions, concepts of operation, operations management tools and other functional components. Existing studies have, however, not thoroughly analyzed the net positive impact of AAM on society and environment to justify investments in its infrastructure and implementation. In this work, we fill this gap by evaluating the non-monetary social impact of AAM in the state of Ohio for passengers, patients, farmers, logistics companies and their customers and bridge inspection entities, as well as its environmental impact, by conducting a thorough data-driven quantitative cost–benefit analysis of AAM from the perspective of the state government. To this end, the most relevant and significant benefit and cost factors are identified, monetized, and estimated. Existing ground transportation for the movement of passengers and goods within and across urban areas is considered as the base case. The findings demonstrate that AAM’s benefits are large and varied, far outweighing its costs. Insights on these benefits can help gain community acceptance of AAM, which is critical for successful implementation of AAM. The findings support decision-making for policymakers and provide justification for investments in AAM infrastructure by the government and private sector.

Visual dysfunction resulting from optic neuritis (ON) is one of the most common clinical manifestations of multiple sclerosis (MS), characterized by loss of retinal ganglion cells, thinning of the nerve fiber layer, and inflammation to the optic nerve. Current treatments available for ON or MS are only partially effective, specifically target the inflammatory phase, and have limited effects on long-term disability. Fingolimod (FTY) is an FDA-approved immunomodulatory agent for MS therapy. The objective of the current study was to evaluate the neuroprotective properties of FTY in the cellular model of ON-associated neuronal damage. R28 retinal neuronal cell damage was induced through treatment with tumor necrosis factor-α (TNFα). In our cell viability analysis, FTY treatment showed significantly reduced TNFα-induced neuronal death. Treatment with FTY attenuated the TNFα-induced changes in cell survival and cell stress signaling molecules. Furthermore, immunofluorescence studies performed using various markers indicated that FTY treatment protects the R28 cells against the TNFα-induced neurodegenerative changes by suppressing reactive oxygen species generation and promoting the expression of neuronal markers. In conclusion, our study suggests neuroprotective effects of FTY in an in vitro model of optic neuritis.

The uncontrolled growth and spread of abnormal cells because of activating protooncogenes and/or inactivating tumor suppressor genes are the hallmarks of cancer. The PI3K/Akt signaling is one of the most frequently activated pathways in cancer cells responsible for the regulation of cell survival and proliferation in stress and hypoxic conditions during oncogenesis. Non-coding RNAs are a large family of RNAs that are not involved in protein-coding, and microRNAs (miRNAs) are a sub-set of non-coding RNAs with a single strand of 18–25 nucleotides. miRNAs are extensively involved in the post-transcriptional regulation of gene expression and play an extensive role in the regulatory mechanisms including cell differentiation, proliferation, apoptosis, and tumorigenesis. The impact of cancer on mRNA stability and translation efficiency is extensive and therefore, cancerous tissues exhibit drastic alterations in the expression of miRNAs. miRNAs can be modulated by utilizing techniques such as miRNA mimics, miRNA antagonists, or CRISPR/Cas9. In addition to their capacity as potential targets in cancer therapy, they can be used as reliable biomarkers to diagnose the disease at the earliest stage. Recent evidence indicates that microRNA-mediated gene regulation intersects with the Akt pathway, forming an Akt-microRNA regulatory network. miRNAs and Akt in this network operate together to exert their cellular tasks. In the current review, we discuss the Akt-associated miRNAs in several cancers, their molecular regulation, and how this newly emerging knowledge may contribute greatly to revolutionize cancer therapy.

Despite valvular heart diseases constituting a significant medical problem, the acquisition of information describing their pathophysiology remains difficult. Due to valvular size, role and location within the body, there is a need for in vitro systems that can recapitulate disease onset and progression. This study combines the development of an in vitro model and its application in the mechanical stimulation of valvular cell transformation. Specifically, porcine aortic valvular interstitial cells (PAVIC) were cultured on polydimethylsiloxane microfluidic devices with or without exposure to shear stresses. Mechanobiological responses of valvular interstitial cells were evaluated at shear stresses ranging from 0 to 4.26 dyn/cm2. When flow rates were higher than 0.78 dyn/cm2, cells elongated and aligned with the flow direction. In addition, we found that shear stress enhanced the formation of focal adhesions and up-regulated PAVIC transformation, assessed by increased expression of α-smooth muscle actin and transforming growth factor β. This study reveals a link between the action of shear forces, cell phenotype transformation and focal adhesion formation. This constitutes the first step towards the development of co-cultures (interstitial-endothelial cells) on organ-on-a-chip devices, which will enable studies of the signaling pathways regulating force-induced valvular degeneration in microtissues and potential discovery of valvular degeneration therapies.

Degenerative valvular diseases have been linked to the action of abnormal forces on valve tissues during each cardiac cycle. It is now accepted that the degenerative behavior of valvular cells can be induced mechanically in vitro. This approach of in vitro modeling of valvular cells in culture constitutes a powerful tool to study, characterize, and develop predictors of heart valve degeneration in vivo. Using such in vitro systems, we expect to determine the exact signaling mechanisms that trigger and mediate propagation of degenerative signals. In this study, we aim to uncover the role of mechanosensing proteins on valvular cell membranes. These can be cell receptors and triggers of downstream pathways that are activated upon the action of cyclical tensile strains in pathophysiological conditions. In order to identify mechanosensors of tensile stresses on valvular interstitial cells, we employed biaxial cyclic strain of valvular cells in culture and quantitatively evaluated the expression of cell membrane proteins using a targeted protein array and interactome analyses. This approach yielded a high-throughput screening of all cell surface proteins involved in sensing mechanical stimuli. In this study, we were able to identify the cell membrane proteins which are activated during physiological cyclic tensile stresses of valvular cells. The proteins identified in this study were clustered into four interactomes, which included CC chemokine ligands, thrombospondin (adhesive glycoproteins), growth factors, and interleukins. The expression levels of these proteins generally indicated that cells tend to increase adhesive efforts to counteract the action of mechanical forces. This is the first study of this kind used to comprehensively identify the mechanosensitive proteins in valvular cells.

Background: Food drug interactions contribute a major reason for drug interactions but they are neglected due to less knowledge and awareness on it. Objective: To assess the awareness about food drug interactions among various individuals from diverse backgrounds. Methodology: This is the prospective questionnaire study comprising of 12 questions, each question have both right and wrong options, where as the last question is opinion based. The questionnaire was formatted in a simple and easy manner for the understanding of individuals from non-medical field. These forms were circulated online and the responses were collected. Results: Thirty nine out of forty five responses from doctors were valid in which 65.55% were correct, 23.46% were wrong and 9.66% were unaware, similarly out of thirty three, twenty four responses from nurses were valid in which 44.07% were correct, 49.72% were wrong and 5.65% were unaware. From a total of 102 responses from clinical pharmacologists 81 were valid in which 72.27% were correct, 24.75% were wrong and 0.99% was unaware. Discussion: Geriatric population is highly susceptible to food drug interactions due to polypharmacy and altered levels in absorption, distribution, metabolism and elimination. The study was successful in assessing the knowledge about food drug interactions in individuals from diverse backgrounds. Conclusion: The clinical pharmacologists had more awareness on food drug interaction than doctors and nurses. The study findings support the need for nurses and doctors to update their practice through additional training and integration of knowledge and expertise about food drug interactions to improve the therapeutic efficacy, drug compliance and safety of patients.

Decades of research have elucidated the critical role of Akt isoforms in cancer as pro-tumorigenic and metastatic regulators through their specific effects on the cancer cells, tumor endothelial cells and the stromal cells. The pro-cancerous role of Akt isoforms through enhanced cell proliferation and suppression of apoptosis in cancer cells and the cells in the tumor microenvironment is considered a dogma. Intriguingly, studies also indicate that the Akt pathway is essential to protect the endothelial-barrier and prevent aberrant vascular permeability, which is also integral to tumor perfusion and metastasis. To complicate this further, a flurry of recent reports strongly indicates the metastasis suppressive role of Akt, Akt1 in particular in various cancer types. These reports emanated from different laboratories have elegantly demonstrated the paradoxical effect of Akt1 on cancer cell epithelial-to-mesenchymal transition, invasion, tumor endothelial-barrier disruption, and cancer metastasis. Here, we emphasize on the specific role of Akt1 in mediating tumor cell-vasculature reciprocity during the advanced stages of cancers and discuss how Akt1 differentially regulates cancer metastasis through mechanisms distinct from its pro-tumorigenic effects. Since Akt is integral for insulin signaling, endothelial function, and metabolic regulation, we also attempt to shed some light on the specific effects of diabetes in modulating Akt pathway in the promotion of tumor growth and metastasis.

The aim of this paper is to consider the relation between Lie-isoclinism and isomorphism of two pairs of Leibniz algebras. We show that, unlike the absolute case for finite dimensional Lie algebras, these concepts are not identical, even if the pairs of Leibniz algebras are Lie-stem. Moreover, throughout the paper we provide some conditions under which Lie-isoclinism and isomorphism of Lie-stem Leibniz algebras are equal. In order to get this equality, the concept of factor set is studied as well., 20 page

valvular interstitial cells (qVICs) resembling fibroblasts. In diseased valves, a myofibroblastic phenotype, activated VICs (aVICs), is highly proliferative, synthesize extracellular matrix and repair/remodel the valve. Adult valves also have an understudied small population of progenitor cells (pVIC), which can differentiate into other VIC phenotypes. A better understanding is needed for the role of pVIC in valvular pathophysiology. We hypothesize that pVICs mediate deactivation of VICs, to control or prevent pathological development. Methods: In this study, we isolated two subpopulations of pVICs, Mesenchymal Stem Cells (MSC) and Hematopoietic Stem Cells (HSC), and evaluated their role in myofibroblastic deactivation of VICs. Porcine pVIC subpopulations were magnetically isolated with CD90 and CD34 respectively serving as markers of MSC and HSC. MSC and HSC subpopulations were validated using secondary MSC and HSC markers CD105 and CD117 respectively. Three culture types were designed. Results: A pVIC-supplemented culture was created by increasing pVIC concentration in VIC population by 50% (positive response) Native culture maintained pVIC concentration identical to native valves postharvest (physiologic response). Negative culture had pVICs removed (negative response). Supplemented culture with MSC subpopulation did not have any effect on VIC activation. Supplemented culture with HSC subpopulation induced deactivation in VICs. Conclusion: To our knowledge, this is one of the first observations of pVIC subpopulations mediating myofibroblastic deactivation in VICs and further studies are needed for a more detailed understanding of pVIC function in valvular biology.

The aim of the present study was to investigate the phytochemistry and bioactive nature of Tridax procumbens. The ethanol, benzene and petroleum ether extracts of dried roots of this plant were investigated for phytochemistry and antibacterial analysis. The antibacterial activity was evaluated against different bacterial strains viz. Escherichia coli, Staphylococcus aureus, Salmonella typhii, Klebsiella pneumoniae and Shigella flaxineri by detecting zone of inhibition. The zone of inhibition was compared with standard discs of Gentamicin. From these extracts, two of them (ethanolic and pet-ether extracts) revealed significant results as compared to benzene extract. The qualitative analysis revealed the presence of flavonoids, pholabatannins, resins, tannins, phenols, lipids and fats and carbohydrates.

Microorganisms adhere to uroepitelium and trigger adaptive immune response with synthesis of chemokine’s and cytokines. Chemokine and chemokine receptors lead to recruitment of inflammatory cells results in inflammatory response: healing or scaring. FcR initiates effector functions: degranulation, cytokine, superoxide production, and arrangement of antibody synthesis, antibody dependent cellular cytotoxicity, and phagocytosis. Aim was to determine FcγR polymorphism role in urinary tract infection (UTI). 131 UTI and 151 healthy subjects without any urinary tract abnormality were participated. Polymorphisms were determined by amplification refractory mutation system PCR. FcγRIIa R/R genotype and FcγRIIa R allele are found significantly higher in study group than control. FcγRIIIa genotype distribution and allele frequency is not significantly different between UTI and control group. FcγRIIIb-NA2/NA2 genotype and NA2 allele are found statistically higher when compared to control FcgRIIa-131-R allele is found to be related; lower UTI (p=0.015), gram negative bacterial infection risk (p=0.012) FcgRIIIb-NA2 allele is found to be related; upper UTI (p=0.001) gram negative bacterial infection (p=0.001), renal scar development risk (p=0.001). FcγRIIa-R131R and FcγRIIIb-NA2/NA2 gene polymorphisms may increase risk and susceptibility to UTI in children.

Cancer is a disease in wh ich cells grow abnormally in a group, uncontrollably deviating from the normal rules of cell division. It is regarded as the leading cause of death in economically developed countries and the second leading cause in developing countries. Cancer rates in In dia are lower than those seen in western countries, owing to the diverse populations and diets. The rate of colorectal, prostate and lung cancer in India are one of the lowest. Prevention of diseases through healthy diet and eating habits has been recogniz ed in various mythological books. Turmeric or curcumin which is a common ingredient in the Indian curries has shown anti - oxi dant and anti - inflammatory action, which helps it to act as a chemo - pr otective agent . The role of curcumin includes inhibition at mu ltiple levels of several cell signaling pathways. The use of turmeric in Indian dishes could be a reason for low cancer rates; hence turmeric can be included in diet to prevent the development of tumor.

Since most of the body&rsquo, s extracellular matrix (ECM) is composed of collagen and elastin, we believe the choice of these materials is key for the future and promise of tissue engineering. Once it is known how elastin content of ECM guides cellular behavior (in 2D or 3D), one will be able to harness the power of collagen-elastin microenvironments to design and engineer stimuli-responsive tissues. Moreover, the implementation of such matrices to promote endothelial-mesenchymal transition of primary endothelial cells constitutes a powerful tool to engineer 3D tissues. Here, we design a 3D collagen-elastin scaffold to mimic the native ECM of heart valves, by providing the strength of collagen layers, as well as elasticity. Valve interstitial cells (VICs) were encapsulated in the collagen-elastin hydrogels and valve endothelial cells (VECs) cultured onto the surface to create an in vitro 3D VEC-VIC co-culture. Over a seven-day period, VICs had stable expression levels of integrin &beta, 1 and F-actin and continuously proliferated, while cell morphology changed to more elongated. VECs maintained endothelial phenotype up to day five, as indicated by low expression of F-actin and integrin &beta, 1, while transformed VECs accounted for less than 7% of the total VECs in culture. On day seven, over 20% VECs were transformed to mesenchymal phenotype, indicated by increased actin filaments and higher expression of integrin &beta, 1. These findings demonstrate that our 3D collagen-elastin scaffolds provided a novel tool to study cell-cell or cell-matrix interactions in vitro, promoting advances in the current knowledge of valvular endothelial cell mesenchymal transition.

Clinical trials are a series of studies that help evaluate the safety and efficacy of a newly discovered drug. Although government funds around 80% of basic research to discover new drugs, it does not sponsor clinical trials at a competent level. Most of the trials are financially supported by pharmaceutical companies which arecertainly a worthwhile contribution to drug discovery, but it also influences the outcome of a clinical trial by ensuring acceptable government policies. Studies revealed that industries often practice selective reporting where unfavorable results are concealed, and positive outcomes are over-published, thereby misleading policies and future research. These downsides can be countered by utilizing funds that are totally devoid of industrial interference. It was reported that medical practitioners widely accept results from government-funded research studies and degrade the integrity of industry-funded clinical trials. Government-funded clinical trials virtually result in flawless conclusions which are extensively accepted and employed in conducting future research. Unlike industry-funded research work, government-funded trials emphasize on the need of the hour and deliver a quality result which is witnessed by the emergence of 93 Nobel Prize winners through the National Institutes of Health funded research work. A survey study revealed that 68% of respondents endorsed for doubling government funds for drug development. Utilizing standard methodologies from health economics such as cost-effective analysis and health technology assessment and public–private collaborations can be a solution for several developing and underdeveloped countries which cannot afford to sponsor drug research on its own.

The goal of this research was to use recent advances in the global positioning system (GPS) and computer technology to apply just the right amount of fumigant where it is most needed (i.e., tree-planting-site-specific application) to decrease the incidence of replant disease, and achieve the environmental and economical benefits of reducing the application of these toxic chemicals. In the first year of this study, we retrofitted a chemical applicator with a high-performance GPS receiver (accuracy in the range of 10 to 20 cm), an embedded controller to tend GPS data and control a solenoid valve to implement tree-planting-site-specific fumigant application. Although the system worked well, the results of accuracy tests indicated that the RMS error in position location was 33.5 cm, which was greater than desired. To improve the position location accuracy, a new system was developed during the second year of this study. In this system, the embedded controller which was slow to perform all the necessary computations in real-time was replaced with a higher speed controller. Moreover, a pulse width control module (PWM) and solenoid actuated nozzles were also included to provide precise application rate on demand. Extensive testing indicated that the new system had a RMS error of less than 15 cm. The system was field tested in three almond orchards in California during Fall of 2007. The system performed well in all three locations.�

The oriental eye fly Siphunculina funicola, a small member (1.5-1.6 mm) of the family Chloropidae, is extremely annoying to humans and domestic animals, feeding on mucous membranes, secretions, and other moist surfaces of their hosts. In central Thailand heavy populations were detected during 2006-2007 in some rural, agricultural, and periurban areas of the region. They were noted to exhibit strong synanthropy and aggregation behavior, congregating on thin (1-5 mm diam) substrates hanging in or near human habitations and animal shelters and other structures open on one or more sides. We initiated studies on the repelling and control of this eye fly at their aggregation sites, the most vulnerable targets near or in human habitations. Four formulations of repellents consisting of Everside, 3 fatty acids (with 8, 9, and 10 carbons), permethrin, and the acids C8910 plus permethrin in Everside were diluted 1:3 in tap water and sprayed on to the aggregation sites. Prior to treatment all sites including controls were disturbed to dislodge eye flies, and then the blank sites were sprayed with the aqueous suspension of the repellents. Additionally, we evaluated 3 commercially available household insecticidal aerosol formulations by treating eye flies and their resting sites (without dislodging the flies) with puffs of the aerosols. Two treatments with permethrin alone and permethrin plus acids in Nakhorn Ratchasima Province caused a complete absence of flies from the sites up to 23 h. After treatment with the repellents, the repelled flies and others were found to congregate on untreated favorable sites close to the treated ones. The repellents tested against eye flies in Chonburi Province at 2 locations caused almost complete absence of this insect on aggregation sites up to 120 h. Three household insecticide aerosols applied to aggregation sites with resting and hovering eye flies produced high to complete mortality and reduction of eye flies for 48 h or possibly longer in the treated sites. This is the first time that procedures for the evaluation of repellents and insecticides against eye flies have been tested and developed. The use of commonly available insecticide aerosol products could provide a good source of materials for the elimination of eye flies from their domestic and peridomestic aggregation sites.

Biomedical data useful for data mining are often distributed across multiple databases. These databases may be aggregated using several techniques to create single data sets that may be mined using standard approaches; however, separate databases may, in their design or data representation, capture information that is analytically useful and that is lost on integration. Recent techniques for mining multiple databases simultaneously but separately may preserve and leverage the unique perspectives within each database. This article presents an example, "dual mining," in which concurrent analysis of a target database with a related knowledge base can improve the identification of association patterns in the target most likely to be of interest for further analysis.

To evaluate program and health care costs of a lifestyle intervention in a high-risk obese population.Twelve-month randomized controlled trial comparing lifestyle case management to usual care.Health plan members (n=147) with obesity (body mass index/=27) and type 2 diabetes.Lifestyle case management entailed individual and group education, support, and referrals by registered dietitians. Those in the usual-care group received educational material.Medical and pharmaceutical health care costs reimbursed by the participant's primary insurance company.Total costs were modeled using the four-equation model using previous year cost as a predictor.Net cost of the intervention was $328 per person per year. After incorporating program costs, mean health plan costs were $3,586 (95% confidence interval [CI]: -$8,036, -$25, P0.05) lower in case management compared to usual care. The difference was driven by group differences in medical (-$3,316, 95% CI: -$7,829 to -$320, P0.05) but not pharmaceutical costs (-$239, 95% CI: -$870 to $280, not statistically significant), with fewer inpatient admissions and costs among case management compared with usual care (admission prevalence: 2.8% vs 22.5% respectively, P0.001).Addition of a modest-cost, registered dietitian-led lifestyle case-management intervention to usual medical care did not increase health care costs and suggested modest cost savings among obese patients with type 2 diabetes. Larger trials are needed to determine whether these results can be replicated in a broader population. The findings can be judiciously applied to support that the addition of a registered dietitian-led lifestyle case-management program to medical care does not increase health care costs.

Context Despite multiple attempts to document and quantify the danger of venous thromboembolism (VTE) following prolonged travel, there is still uncertainty about the magnitude of risk and what can be done to lower it. Objectives To review the methodologic strength of the literature, estimate the risk of travel-related VTE, evaluate the efficacy of preventive treatments, and develop evidence-based recommendations for practice. Data Sources Studies identified from MEDLINE from 1966 through December 2005, supplemented by a review of the Cochrane Central Registry of Controlled Trials, the Database of Abstracts of Reviews of Effects, and relevant bibliographies. Study Selection We included all clinical studies that either reported primary data concerning travel as a risk factor for VTE or tested preventive measures for travel-related VTE. Data Extraction and Analysis Two reviewers reviewed each study independently to assess inclusion criteria, classify research design, and rate methodologic features. The effect of methodologic differences, VTE risk, and travel duration on VTE rate was evaluated using a logistic regression model. Data Synthesis Twenty-four published reports, totaling 25 studies, met inclusion criteria (6 case-control studies, 10 cohort studies, and 9 randomized controlled trials). Method of screening for VTE [screening ultrasound compared to usual clinical care, odds ratio (OR) 390], outcome measure [all VTE compared to pulmonary embolism (PE) only, OR 21], duration of travel (

PubMed ID: 27313313, Background and objectives: Vitamin D deficiency is endemic in children with CKD.We sought to investigate the association of genetic disposition, environmental factors, vitamin D supplementation, and renal function on vitamin D status in children with CKD. Design, setting, participants, & measurements Serum: 25-hydroxy-vitamin D, 1,25-dihydroxy-vitamin D, and 24,25-dihydroxy-vitamin D concentrations were measured cross-sectionally in 500 children from 12 European countries with CKD stages 3-5. All patients were participants of the Cardiovascular Comorbidity in Children with Chronic Kidney Disease Study, had CKD stage 3-5, and were age 6-18 years old. Patients were genotyped for single-nucleotide polymorphisms in the genes encoding 25-hydroxylase, vitamin D binding protein, 7-dehydrocholesterol reductase, and 24-hydroxylase. Associations of genetic status, season, local solar radiation, oral vitamin D supplementation, and disease-associated factors with vitamin D status were assessed. Results: Two thirds of patientswere vitamin D deficient (25-hydroxy-vitamin D

The magnitude of oviposition as well as the size, shape and the number of eggs per of egg rafts egg raft were determined after gravid Culex quinquefasciatus Say oviposited on water treated with water dispersible granules (WDG) of Bacillus thuringiensis ssp. israelensis (Bti) and on untreated water. The mean number of eggs/raft was lower in the treated than in the untreated water. Bti concentrations from 0.5 to 2.0mg/L affected the shape of egg rafts and number of eggs in each raft. As the concentration of Bti increased from 0.5 to 2.0 mg/L the shape of egg rafts became more irregular with fewer eggs in each raft. Exposure to Bti at 2- and 26-h reduced the hatching rates, and fewer eggs hatched at 26-h of exposure to Bti. As the concentration of Bti WDG increased from 0.5 to 2.0 mg/L, the hatching rate decreased. Eggs exposed for 2-h to 2.0mg/ L Bti had a hatch of 30% after 24 h, the rate increasing to 57% after 72 h. In contrast, in 26-h exposed eggs to 2.0 mg/L Bti, the hatching rate after 24 h was only 12% and this rate increased to 39% after 72 h. In larvae from eggs exposed for 2 h, the survival rate was 40% at 2.0 mg/L Bti and 87% in untreated controls. In contrast, the survival rates of larvae from 26-h exposed eggs was 91% in controls while it was 30% at 2.0 mg/L Bti. As the concentration of Bti increased from 0.5 to 2.0 mg/ 1 the survival rates of larvae decreased. The combined effects of reductions of egg rafts, low number of eggs per egg raft, and reduced hatching and survival rates could have significant cumulative effects on the yield of adult mosquitoes, and this could result in a greater control potential of this microbial agent.