Biodegradable and 3D printable lysine functionalized polycaprolactone scaffolds for tissue engineering applications.

Tissue engineering (TE) has sparked interest in creating scaffolds with customizable properties and functional bioactive sites. However, due to limitations in medical practices and manufacturing technologies, it is challenging to replicate complex porous frameworks with appropriate architectures and bioactivity in vitro. To address these challenges, herein, we present a green approach that involves the amino acid (l-lysine) initiated polymerization of ɛ-caprolactone (CL) to produce modified polycaprolactone (PCL) with favorable active sites for TE applications. Further, to better understand the effect of morphology and porosity on cell attachment and proliferation, scaffolds of different geometries with uniform and interconnected pores are designed and fabricated, and their properties are evaluated in comparison with commercial PCL. The scaffold morphology and complex internal micro-architecture are imaged by micro-computed tomography (micro-CT), revealing pore size in the range of ~300-900 µm and porosity ranging from 30 to 70 %, while based on the geometry of scaffolds the compressive strength varied from 143 ± 19 to 214 ± 10 MPa. Additionally, the degradation profiles of fabricated scaffolds are found to be influenced by both the chemical nature and product design, where Lys-PCL-based scaffolds with better porosity and lower crystallinity degraded faster than commercial PCL scaffolds. According to in vitro studies, Lys-PCL scaffolds have produced an environment that is better for cell adhesion and proliferation. Moreover, the scaffold design affects the way cells interact; Lys-PCL with zigzag geometry has demonstrated superior in vitro vitality (>90 %) and proliferation in comparison to other designs. This study emphasizes the importance of enhancing bioactivity while meeting morphology and porosity requirements in the design of scaffolds for tissue engineering applications.

Do Antimonite and Silicon Share the Same Root Uptake Pathway by Lsi1 in Sorghum bicolor L. Moench?

A study was conducted to further develop our understanding of antimony (Sb) uptake in plants. Unlike other metal(loid)s, such as silicon (Si), the mechanisms of Sb uptake are not well understood. However, SbIII is thought to enter the cell via aquaglyceroporins. We investigated if the channel protein Lsi1, which aids in Si uptake, also plays a role in Sb uptake. Seedlings of WT sorghum, with normal silicon accumulation, and its mutant (sblsi1), with low silicon accumulation, were grown in Hoagland solution for 22 days in the growth chamber under controlled conditions. Control, Sb (10 mg Sb L-1), Si (1mM) and Sb + Si (10 mg Sb L-1 + 1 mM Si) were the treatments. After 22 days, root and shoot biomass, the concentration of elements in root and shoot tissues, lipid peroxidation and ascorbate levels, and relative expression of Lsi1 were determined. When mutant plants were exposed to Sb, they showed almost no toxicity symptoms compared to WT plants, indicating that Sb was not toxic to mutant plants. On the other hand, WT plants had decreased root and shoot biomass, increased MDA content and increased Sb uptake compared to mutant plants. In the presence of Sb, we also found that SbLsi1 was downregulated in the roots of WT plants. The results of this experiment support the role of Lsi1 in Sb uptake in sorghum plants.

Silicon alleviates antimony phytotoxicity in giant reed (Arundo donax L.).

MAIN CONCLUSION: Silicon enhances photosynthetic efficiency, biomass, and lignification of root structures possibly limiting antimony translocation and mitigating phytotoxicity in giant reed plants. Antimony (Sb) is a non-essential metalloid causing toxic effects in plants. Silicon has been reported to impart tolerance against biotic and abiotic stress in plants. Fast-growing plant, giant reed (Arundo donax L.) is a promising energy crop, can be a suitable plant for phytoremediation. However, information regarding the tolerance capacity with respect to Sb toxicity and potential of Si to mitigate the Sb phytotoxicity in giant reed are very scarce. Rhizomes of giant reed were grown for ten weeks in hydroponics exposed to Sb, Si, and their combination wherein treatment without Sb/Si served as control. Effect of these treatments on rate of net photosynthesis and photosynthetic pigments, phytoextraction ability of Sb, Si and Sb uptake, plant biomass, and lignification and suberization of roots along with localization of Sb and Si were analysed. We found that Si considerably improved the growth and biomass of giant reed under Sb toxicity. Antimony reduced the photosynthesis and decreased the content of photosynthetic pigments, which was completely alleviated by Si. Silicon amendment to Sb treated plants enhanced root lignification. Silicon enhanced lignification of root structures probably restricted the Sb translocation. However, co-localization of Sb with Si has not been observed neither at the shoot nor at the root levels. Similarly, Sb was also not detected in leaf phytoliths. These findings suggest that Si treatment promotes overall plant growth by improving photosynthetic parameters and decreasing Sb translocation from root to shoot in giant reed by improving root lignification.

Genome Characterization, Comparison and Phylogenetic Analysis of Complete Mitochondrial Genome of Evolvulus alsinoides Reveals Highly Rearranged Gene Order in Solanales.

Mitogenome sequencing provides an understanding of the evolutionary mechanism of mitogenome formation, mechanisms driving plant gene order, genome structure, and migration sequences. Data on the mitochondrial genome for family Convolvulaceae members is lacking. E. alsinoides, also known as shankhpushpi, is an important medicinal plant under the family Convolvulaceae, widely used in the Ayurvedic system of medicine. We identified the mitogenome of E. alsinoides using the Illumina mate-pair sequencing platform, and annotated using bioinformatics approaches in the present study. The mitogenome of E. alsinoides was 344184 bp in length and comprised 46 unique coding genes, including 31 protein-coding genes (PCGs), 12 tRNA genes, and 3 rRNA genes. The secondary structure of tRNAs shows that all the tRNAs can be folded into canonical clover-leaf secondary structures, except three trnW, trnG, and trnC. Measurement of the skewness of the nucleotide composition showed that the AT and GC skew is positive, indicating higher A's and G's in the mitogenome of E. alsinoides. The Ka/Ks ratios of 11 protein-coding genes (atp1, ccmC, cob, cox1, rps19, rps12, nad3, nad9, atp9, rpl5, nad4L) were <1, indicating that these genes were under purifying selection. Synteny and gene order analysis were performed to identify homologous genes among the related species. Synteny blocks representing nine genes (nad9, nad2, ccmFc, nad1, nad4, nad5, matR, cox1, nad7) were observed in all the species of Solanales. Gene order comparison showed that a high level of gene rearrangement has occurred among all the species of Solanales. The mitogenome data obtained in the present study could be used as the Convolvulaceae family representative for future studies, as there is no complex taxonomic history associated with this plant.

Comparison of the single and combined effects of arsenic and antimony on growth and physiology of giant reed (Arundo donax L.).

Fast-growing plant, giant reed (Arundo donax L.) has been gaining a lot of popularity in the phytoremediation of metal-polluted soils. However, information regarding the physiological background of tolerance and accumulation capacity of A. donax with respect to antimony (Sb), arsenic (As), and their co-contamination are very limited. Rooted stem cuttings were grown for 5 months in hydroponics exposed to Sb (10 mg L-1), As (10 mg L-1), and their combined toxicity (Sb 5 mg L-1 + As 5 mg L-1) wherein treatment without As/Sb served as control. Effect of these treatments on key photosynthetic parameters (rate of net photosynthesis, effective quantum yield of photosystem II, chlorophyll fluorescence, and photosynthetic pigments), phytoextraction ability of metalloids, nutrient uptake, root growth, and lignification were analyzed. Arsenic-containing treatments severely affected root morphology of A. donax compared to Sb/control and plants exposed to As showed intensive lignification already in young apical part of the root in the present study. Shoot concentration was found to be 11.35±0.75 Sb mg kg-1 and 8.97±0.52 As mg kg-1 compared to root concentration of 1028.3±19.1 Sb mg kg-1 and 705.3±69.9 As mg kg-1 in the treatments of Sb and As. Even though Sb and As were translocated to the shoots in relatively small amount, both metalloids significantly decreased the shoot and root growth of A. donax and negatively affected the photosynthetic parameters. Moreover, co-contamination of Sb and As proved to be severely toxic to growth and physiology of A. donax even though the magnitudes of the metalloids used were lower than those of Sb/As alone treatments. In conclusion, Sb and As caused a marked reduction in growth and physiological characteristics of A. donax, opposing its use in phytoremediation of highly contaminated soils. Tolerance capacity of plants to simultaneous presence of As and Sb in the environment is crucial for the successful implementation of phytoremediation since the co-contamination by As and Sb might reduce the efficiency of phytoremediation when using this fast-growing and high biomass-producing plant species.

Aluminum toxicity in plants and its possible mitigation in acid soils by biochar: A review.

Toxicity of aluminum (Al) is a serious problem for agricultural plants, especially due to excessive soil acidification caused by continuous intensive agriculture and modified environmental conditions related with global climate change. Decreased root elongation and shoot growth, reduced biomass production, nutrient imbalance and altered physiological and metabolic processes are responsible for lower yield and crop quality and therefore, decreased variability and productivity of the land. Recently, biochar is gaining popularity for ameliorating metal toxicity in soils. However, there is a lack of comprehensive information regarding the effects of biochar and its functioning. Multiple mechanisms are involved in ameliorating Al toxicity in which inherent properties of biochar influencing Al adsorption, absorption, complexation, cation exchange and electrostatic interaction are considered to play major roles. Modification of biochar to enhance these mechanisms might hold the key for long term solution. Present review indicates gaps for further research. Long term field studies are needed to understand the effects of biochar on Al toxicity.

Relapsed Refractory Hodgkin Lymphoma and Brentuximab Vedotin-Bendamustine Combination Therapy as a Bridge to Transplantation: Real-World Evidence From a Middle-Income Setting and Literature Review.

INTRODUCTION: Despite high cure rates with standard treatment, 30% patients with Hodgkin lymphoma develop relapsed or refractory (R/R) disease. Salvage therapy followed by autologous hematopoietic cell transplantation (HCT) is considered standard of care. Brentuximab Vedotin (Bv) in combination with Bendamustine (B) has been tested in the salvage setting with promising results. MATERIALS AND METHODOLOGY: We conducted a single centre retrospective chart review of patients who received BBv salvage therapy to determine its activity and safety in patients with R/R classical Hodgkin lymphoma (HL). Between May 2011- December 2019, 179 patients were diagnosed with R/R HL. RESULTS: Thirty patients received BBv [median age: 30 (15-59) years, females (n=15)]. Primary refractory disease in 19 patients (63%), and 26 patients (87%) had advanced stage at treatment. Most patients received BBv after 2 prior lines of therapy [n=16 (53%)]. The median number of cycles of BBv were 3 (1-6). The number of BBv cycles delivered as outpatient was 63%. The most common Grade III/IV hematological adverse event was neutropenia [n=21, (70%)], while grade III/IV non-hematological toxicities included infections in 4 (13%), neuropathy in 4(13%), skin rash in 2 (7%), GI toxicities in 3 (10%) and liver dysfunction in 2 (7%) patients. The ORR and CR rates were 79% and 62%, respectively. Seventeen patients (57%) underwent an autologous HCT and 8 (26%) underwent an Allogeneic HCT (all haploidentical). The median follow up time from BBv administration was 12 months. Six patients died: 2 = disease progression, and 4 = non-relapse causes (Infection and sepsis = 2, GVHD=2). In addition to this, one patient progressed soon after HCT and another patient relapsed 22 months post HCT. Three year Overall survival (OS) and Event free survival (EFS) probability post-BBv treatment was 75% and 58%, respectively. OS and EFS analysis based on response (viz., CMR) to BBv demonstrated that patients in CMR had better survival probability [93% (p=0.0022) 3yr-OS and 72% (p=0.038) 3yr-EFS probability]. CONCLUSIONS: BBv is an active and well-tolerated salvage treatment for patients with R/R HL, even in refractory and advanced settings. In middle-income settings, cost constraints and access determine patient uptake of this regimen.

Hybrid Poly(hydroxy urethane)s: Folded-Sheet Morphology and Thermoreversible Adhesion.

Hybrid poly(hydroxy urethane)s (PHUs) are synthesized by copolymerizing aromatic/alicyclic cyclic carbonates with a polyether amine via addition polymerization. They result into polymers with an average molecular weight of 10 kDa and exhibit solubility in common organic solvents. The hybrid PHUs display T g up to 18 °C. PHUs are enriched with multiple H-bonded interactions and they are assessed using temperature-dependent 1H NMR and Fourier-transform infrared studies. PHUs possess folded-sheet morphology with nanogap between folds and nanowidth between chains. The secondary interactions bestow thermoreversible property to PHUs, and they display good adhesion to both polar (Al-Al) and nonpolar (HDPE-HDPE) substrates. Hybrid PHUs show improved optical transparency compared to homo PHUs. The PHUs are thermally stable up to 250 °C.

In Situ Synthesis of Silver Nanospheres, Nanocubes, and Nanowires over Boron-Doped Graphene Sheets for Surface-Enhanced Raman Scattering Application and Enzyme-Free Detection of Hydrogen Peroxide.

An effective in situ synthesis strategy is demonstrated for the preparation of silver nanostructures (nanospheres (NSs), nanocubes (NCs), and nanowires (NWs)) on the surface of boron-doped graphene (BG). Further, these functional nanomaterials are employed for the surface-enhanced Raman scattering (SERS) and non-enzymatic electrochemical detection of H2O2. The results confirm the superior performance of BG-Ag nanostructures as SERS platform. Among various geometries of silver nanoparticles studied in this work, we find that the AgNCs over BG (BG-AgNC) present outstanding SERS performance for detecting 4-mercaptobenzoic acid, with a limit of detection of 1.0 × 10-13 M. Furthermore, BG-AgNC exhibits excellent capability to detect melamine as low as 1.0 × 10-9 M. Electrochemical results confirm that the BG-AgNW-based platform exhibits a superior biosensing performance toward H2O2 detection. The enhanced performance is due to the presence of graphene, which improves the conductivity and provides more active sites. The synthesis of doped graphene with metallic nanoparticles described in this work is expected to be a key strategy for the development of an efficient SERS and electrochemical sensor that offers simplicity, cost-effectiveness, long-term stability, and better reproducibility.

Cardiorespiratory Fitness (Peak Oxygen Uptake): Safe and Effective Measure for Cardiovascular Screening Before Kidney Transplant.

BACKGROUND: Significant heterogeneity exists in practice patterns and algorithms used for cardiac screening before kidney transplant. Cardiorespiratory fitness, as measured by peak oxygen uptake (VO2peak), is an established validated predictor of future cardiovascular morbidity and mortality in both healthy and diseased populations. The literature supports its use among asymptomatic patients in abrogating the need for further cardiac testing. METHODS AND RESULTS: We outlined a pre-renal transplant screening algorithm to incorporate VO2peak testing among a population of asymptomatic high-risk patients (with diabetes mellitus and/or >50 years of age). Only those with VO2peak <17 mL/kg per minute (equivalent to <5 metabolic equivalents) underwent further noninvasive cardiac screening tests. We conducted a retrospective study of the a priori dichotomization of the VO2peak <17 versus ≥17 mL/kg per minute to determine negative and positive predictive value of future cardiac events and all-cause mortality. We report a high (>90%) negative predictive value, indicating that VO2peak ≥17 mL/kg per minute is effective to rule out future cardiac events and all-cause mortality. However, lower VO2peak had low positive predictive value and should not be used as a reliable metric to predict future cardiac events and/or mortality. In addition, a simple mathematical calculation documented a cost savings of ≈$272 600 in the cardiac screening among our study cohort of 637 patients undergoing evaluation for kidney and/or pancreas transplant. CONCLUSIONS: We conclude that incorporating an objective measure of cardiorespiratory fitness with VO2peak is safe and allows for a cost savings in the cardiovascular screening protocol among higher-risk phenotype (with diabetes mellitus and >50 years of age) being evaluated for kidney transplant.

Management of Cervically Fractured Central Incisors: A Multidisciplinary Approach.

INTRODUCTION: Fracture of tooth structure at or below the gingival margin compromises rehabilitation and hampers esthetics and function. MANAGEMENT: Management of such cases by a post-core and crown restoration, or periodontal surgery or orthodontic extrusion alone may not always suffice in attaining a good result. CASE REPORT: A multi-disciplinary approach which includes all of the above mentioned procedures helps in long term success. CONCLUSION: Careful case evaluation, treatment planning and meticulous attention to detail are the keys to the best treatment outcome.

Proton Pump Inhibitor Use and Risk of Hip Fracture in Kidney Transplant Recipients.

BACKGROUND: Posttransplantation bone disease is a significant problem, with few well-evidenced therapeutic options. Proton pump inhibitors (PPIs) are associated with hip fracture in the general population and are widely prescribed for kidney transplant recipients. STUDY DESIGN: A case-control study. SETTING & PARTICIPANTS: From the US Renal Data System, we identified from diagnoses and procedures 231 kidney transplant recipients with a first hip fracture. Cases were matched at the hip fracture index date with 15,575 controls on age, sex, race, and transplantation year. PREDICTOR: PPI use. OUTCOMES: First hip fracture. RESULTS: In the year prior to the index date, a PPI was prescribed to 65.4% of cases and 57.4% of controls. Additionally, in 34.6% of cases and 28.9% of controls, a PPI was prescribed for >80% of the year preceding the index date (higher PPI users). Unadjusted ORs of hip fracture associated with any and higher PPI use were 1.55 (95% CI, 1.18-2.05) and 1.65 (95% CI, 1.2-2.27), respectively. When adjusted for baseline demographic, clinical, and pharmacologic covariables, any and higher PPI use remained associated with hip fracture, with ORs of 1.39 (95% CI, 1.04-1.84) and 1.41 (95% CI, 1.02-1.95), respectively. LIMITATIONS: Potential residual confounding through either incorrectly ascertained or unavailable confounders; cohort limited to Medicare beneficiaries receiving low-income subsidy. CONCLUSIONS: In summary, PPI use was associated with hip fracture risk in the US kidney transplant population.

Low-grade papillary adenocarcinoma of nasopharynx with expression of thyroid transcription factor-1: Case report and review of literature.

Low-grade papillary adenocarcinomas with expression of thyroid transcription factor-1 (TTF-1) are rare tumors of the nasopharynx, with only a few cases reported in the literature. These tumors have an excellent prognosis following complete surgical excision. We report a 13-year-old boy with this rare tumor in the nasopharynx. The patient underwent complete surgical excision of the tumor and was on follow-up without evidence of recurrence.

Mucoepidermoid carcinoma of parotid gland as a subsequent neoplasm in children treated for acute lymphoblastic leukemia.

We report two cases of mucoepidermoid carcinoma occurring as a second neoplasm following treatment for acute lymphoblastic leukemia. Both patients underwent parotidectomy as the primary treatment. One of them received irradiation in addition to surgery. We discuss the risk of developing MEC as a second malignancy, prognosis, and treatment options.

Comparative cytomorphometric analysis of oral mucosal cells in normal, tobacco users, oral leukoplakia and oral squamous cell carcinoma.

BACKGROUND: Squamous cell carcinoma (SCC) is the third most common cause of oral morbidity in India despite the numerous advances made in the treatment protocol. AIM: To compare the cytomorphometric changes of oral mucosal cells in normal subjects (Group I) with that of tobacco users without any lesion (Group II), tobacco users with oral leukoplakia (Group III), and tobacco users with oral SCC (Group IV) through a semi-automated image analysis system. MATERIALS AND METHODS: Oral mucosal cells collected from study subjects (n = 100) stained using rapid Papanicolaou stain. Photomicrograph of 50 nonoverlapping cells captured at 50× magnification with a digital image capture system. Cytomorphometric analysis of cells in the captured images was performed with Image-Pro image analysis software. Image analysis was performed to obtain cell diameter (CD), cytoplasmic area (CyA), nuclear diameter (ND), nuclear area (NA), and nuclear-to-cytoplasmic ratio. These values were statistically compared among the groups using one-way analysis of variance (ANOVA) and Mann-Whitney U test. RESULTS: The ND, NA, and nuclear-to-cytoplasmic ratio values were found to be increased in the samples collected from leukoplakia and oral SCC. The CD and CyA decreased compared to the normal mucosa in oral SCC samples. CONCLUSION: The cytomorphometric changes observed in samples from oral SCC and oral leukoplakia were consistent with the current diagnostic features. Hence, the semi-automated cytomorphometric analysis of oral mucosal cells can be used as an objective adjunct diagnostic tool in the diagnosis of these lesions.

Comparison of outcomes from smoking and nonsmoking donors: thirteen-year experience.

BACKGROUND: Lung transplantation remains the best treatment option for a variety of end-stage lung diseases. Pressure on the limited donor pool has led to the use of extended criteria donors. One aspect of this has been the liberalization of the use of smoking donors (SmD). METHODS: This study is a retrospective review of lung transplants performed between April 1995 and August 2008 at a single institute. We examined the impact of donor smoking on short-term and long-term survival in relationship to recipient and donor demographics such as ischemic time, cytomegalovirus status, rates of rejection and infection, ventilation, and intensive care stay. Endpoints were survival, infection, and rejection. RESULTS: During this 13-year period, 454 lung transplants were performed. Smoking history was available on 424 (93.4%) of these (SmD, n = 184; NSmD, n = 240). Seventy-one patients died within 3 months of transplant leaving 353 alive at 3 months posttransplant. Fatalities within the first 3 months were significantly higher in the SmD group (21% vs 13%, odds ratio 1.9, hazard ratio 3.3, p = 0.04). No significant difference in rejection and infection rates between recipients of lungs from SmD and NSmD at 3 months and at 1 year posttransplantation (p = 0.51 and 0.09) was found. Although recipients of lungs from SmD had higher odds of ventilation for more than 10 hours, the odds were only increased by 20%, which was not statistically significant. Recipients from SmD had significantly longer stays in the intensive care (odds ratio 1.9, p = 0.002). There was little evidence for an effect of SmD on the development of bronchiolitis obliterans. CONCLUSIONS: In this large cohort of patients, donor smoking history has an effect on early survival but no effect on long-term survival. The cause of this early mortality is independent of infection and rejection. However, these data suggest that overall outcomes from the use of donor lungs from smokers are acceptable, particularly in the current era with limited donor organs.

Growth of Escherichia coli in iron-enriched medium increases HPI catalase activity.

Escherichia coli has two catalases, HPI and HPII. HPI is induced during logarithmic growth in response to low concentrations of hydrogen peroxide. This induction is OxyR-dependent. On the other hand, HPII is not peroxide-inducible but is induced in entry to the stationary phase. We demonstrate here that E. coli displayed higher HPI catalase activity when compared to the cultures that were grown in a normal medium, if grown in a medium supplemented with iron-citrate. Iron supplementation had no effect on HPII catalase. This increase of HPI activity was OxyR-independent and not observed in a Deltafur mutant. The physiological significance of the increase of HPI activity is unclear, but it appears that the katG gene that codes for HPI catalase is among the genes that are regulated by Fur.