Long-Term Outcomes of Hallux Amputations at Various Anatomic Levels.

Hallux amputations have long been performed for the definitive treatment of hallux osteomyelitis resulting from ulcerations. These amputations have been performed at various levels of the hallux. The aim of this study is to assess the long-term outcomes in patients with hallux amputations performed at these various levels and to determine whether there is an ideal anatomic level that would limit post-operative complications and need for revisional surgery. An Institutional Review Board (IRB)-approved retrospective chart review of 148 feet with hallux amputations performed at various levels from July 1, 2013 to July 16, 2020 at an academic medical center was conducted. A 2-year minimum follow up was required for inclusion in the study. Incidence of re-ulceration, need for further amputation, healing of index procedure, and revascularization status were evaluated. Statistical analysis utilizing chi square analysis was performed to calculate p-values where <.05 was statistically significant. In this retrospective study with a minimum of 2-year follow-up, there was a tendency for amputations performed at the level of the head of the proximal phalanx (21%) to have a lower rate of reulceration (24%) followed by amputations performed at the level of the metatarsophalangeal joint and interphalangeal joints (36%). However, neither proved to be statistically significant.

A rare case of Philadelphia-positive (P210BCR-ABL1) T-cell acute lymphoblastic leukemia/lymphoma associated with minimal residual disease persistence after intensive chemotherapeutic approaches.

T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is a rare and aggressive leukemia. Philadelphia chromosome-positive cytogenetic abnormality is most common in CML. It is difficult to differentiate between de novo Ph+ T-ALL/LBL and T-cell lymphoblastic crises of CML. We present a case of adult Ph+ T-ALL/LBL with a likely history of antecedent CML. Initially thought to be a case of chronic-phase CML, a diagnostic quandary led to the pursuit of a lymph node biopsy that established the diagnosis of Ph+ T-LBL or T lymphoblastic blast crisis of CML, a clinical presentation extremely rare and only the second of its kind from our review of the literature. The patient was treated with an intensive chemotherapy regimen for over a year due to persistent minimal residual disease (MRD) positivity indicating aggressive disease.

Identification and quantification of chain-pairing variants or mispaired species of asymmetric monovalent bispecific IgG1 monoclonal antibody format using reverse-phase polyphenyl chromatography coupled electrospray ionization mass spectrometry.

Developing a knob-into-hole asymmetric bispecific IgG1 monoclonal antibody (mAb) poses manufacturing challenges due to the expression of chain pairing variants, also called mispaired species, in the desired product. The incorrect pairing of light and heavy chains could result in heterogeneous mispaired species of homodimers, heterodimers, light chain swapping, and low molecular weight species (LMWS). Standard chromatography, capillary electrophoretic, or spectroscopic methods poorly resolve these from the main variants. Here, we report a highly sensitive reverse-phase polyphenyl ultra-high-performance liquid chromatography (RP-UHPLC) method to accurately measure mispaired species of Duet mAb format, an asymmetric IgG1 bispecific mAb, for both process development and quality control analytical tests. Coupled with electrospray ionization mass spectrometry (ESI-MS), it enabled direct online characterization of mispaired species. This single direct assay detected diverse mispaired IgG-like species and LMWS. The method resolved eight disulfide bonds dissociated LMWS and three mispaired LMWS. It also resolved three different types of IgG-like mispaired species, including two homodimers and one heterodimer. The characterization and quantification simultaneously enabled the cell line selection that produces a lesser heterogeneity and lower levels of mispaired species with the desired correctly paired product. The biological activity assessment of samples with increased levels of these species quantified by the method exhibited a linear decline in potency with increasing levels of mispaired species in the desired product. We also demonstrated the utility of the technique for testing in-process intermediate materials to determine and assess downstream purification process capability in removing diverse mispaired IgG-like species and LMWS to a certain level during the downstream purification process. Our investigation demonstrates that adopting this method was vital in developing asymmetric bispecific mAb from the initial stage of cell line development to manufacturing process development. Therefore, this tool could be used in the control strategy to monitor and control mispaired species during manufacturing, thus improving the quality control of the final product.

Efficacy of CD19 directed therapies in patients with relapsed or refractory large b-cell lymphoma relapsing after CD19 directed chimeric antigen receptor T-cell therapy.

Outcomes are poor for patients with relapsed and/or refractory (R/R) large B-cell lymphoma (LBCL) post chimeric antigen receptor T-cell (CAR-T) therapy. Two CD19-directed therapies, tafasitamab- cxix plus lenalidomide (tafa-len) and loncastuximab tesirine (loncaT) are approved in R/R LBCL. The efficacy of these CD19 directed therapies in patients who relapse after CD19 directed CAR-T (CD19-CART) therapy is not well understood. We conducted a multi-center study of patients with R/R LBCL that received either tafa-len or loncaT at any timepoint for R/R disease after CD19-CART therapy. Fifty-three patients were included in this study with the median follow up of 56 (9.1-199) weeks from CAR-T infusion. Median number of systemic therapies pre-CAR-T therapy was 3 (range: 1-6); axicabtagene ciloleucel was the most utilized CAR-T product (n = 32,60%). Median time from CAR-T therapy to tafa-len or loncaT was 7.3 (1.2-38.2) months with median number of lines of therapy between CAR-T therapy and these regimens of 1 (0-5). Combined overall response rate and complete response rates were 27% and 10%, respectively. Median duration of response was 13.3 (2.1-56.7) weeks. In this real-world study, the use of currently approved CD19-directed therapies to treat R/R LBCL after CD19-CAR-T therapy showed limited clinical activity and duration of responses.

Primary cardiac large B cell lymphoma.

A female patient in her mid-60s presented with progressive shortness of breath, pleuritic chest pain and bilateral leg swelling for 1 week. Initial diagnostic workup revealed pericardial effusion, and a localised pericardial tubular mass on CT chest. Pericardial fluid analysis showed elevated white cells, with predominance of medium-large sized atypical lymphoid cells. Atypical lymphocytes stained positive for CD79a, CD10, PAX-5, BCL-2 and BCL6. Fluorescence in situ hybridisation testing demonstrated MYC and BCL6 rearrangements without BCL2 gene rearrangement. The overall morphological, immunohistochemical and cytogenetic findings supported a diagnosis of high-grade B cell lymphoma with MYC and BCL6 rearrangements. After extensive staging workup, localised disease involving the pericardium with a diagnosis of primary cardiac large B cell lymphoma was established. She was treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab chemotherapy. Rituximab was discontinued owing to largely absent CD20 expression. Interim positron emission tomography-CT after three cycles revealed a complete response, and the patient completed six cycles of therapy.

Expression of ER, PR, and HER-2 Neu and correlation with tumor markers in gall bladder carcinoma.

Background: Females having a large proportion of gallbladder carcinoma (GBC) and a higher incidence of gallstones pointed toward the role of sex hormones in GBC development. In this study, we evaluated the expression of Estrogen receptor (ER), Progesterone receptor (PR), and Her2/neu and their correlation with tumor markers and clinicopathological parameters in the GBC. Methods: A total of 50 patients of GBC and 42 patients in control group undergoing surgery for other conditions were taken. The patient's biopsy sample's paraffin block was tested for ER, PR, and Her2/neu expression by immunohistochemistry. Results: ER and PR had no significant expression in GBC and control group, but Her2/neu had 16% expression in GBC, significantly associated with the degree of differentiation with 62.5% (n-5) being well-differentiated; 75% of Her2/neu positive were in stages III and IV. Her2/neu did not correlate with tumor markers despite expression. Conclusions: Her2/neu amplification is a small step in validating that option so it could be included in the treatment and prognostication of GBC.

A population level analysis of second hematological malignancies in chronic lymphocytic leukemia/small lymphocytic lymphoma survivors in the era of targeted therapies.

With improvement in survival after chronic lymphocytic leukemia (CLL) diagnosis, the real-world burden of second hematological malignancies (SHM) has not been comprehensively assessed in recent era. We analyzed risk, incidence, and outcomes of SHM in CLL patients between 2000 and 2019 using SEER database. CLL patients had greater risk for hematological malignancies than general population [SIR, standardized incidence ratio (95% CI):2.58 (2.46-2.70); p < 0.05]. The risk for subsequent lymphoma increased by 1.75 folds in 2015-2019 compared to 2000-2004. The duration, after CLL diagnosis, of maximum risk for SHM decreased as 60-119 months for time-period 2000-2004, 6-11 months for 2005-2009 to 2-5 months for 2010-2014 and 2015-2019. Incidence of SHM was 2.5% in CLL survivors (1736/70,346) with lymphoid SHM being more common than myeloid SHM, and DLBCL being the most common pathology (n = 610, 35% of all SHM). Male sex, age ≤65 years at CLL diagnosis, and chemotherapy treatment were associated with higher risk for SHM. The median gap between CLL and SHM diagnoses was 46 months. The median survival for de-novo-AML, t-MN, CML, and aggressive NHL was 63, 86, 95, and 96 months respectively. Although SHM remains rare, there is increased risk in recent era, likely due to improved survival in CLL patients, necessitating active surveillance strategies.

Gastrointestinal treatment-related adverse events of combined immune checkpoint inhibitors: a meta-analysis.

Introduction: Combined immune checkpoint inhibitors can cause gastrointestinal adverse events. Methods: We performed a meta-analysis of pooled colonic, hepatic and pancreatic treatment-related adverse events of combined ICI. Results: 53 trials reporting treatment-related adverse events in 6581 patients. All grade diarrhea was the most common adverse event seen in 25.4% patients, followed by all grade hepatitis in nearly 13% patients and pancreatitis in nearly 7.5% patients. Conclusion: Our study provides pooled data of treatment-related adverse events from different combination immune checkpoint inhibitors use in solid tumors and demonstrates a high incidence of all grades and ≥3 grade gastrointestinal adverse events. Further studies are required to characterize these adverse events and assess their overall impact on treatment course and outcomes.

The article talks about a type of medicine called immune checkpoint inhibitors that are used to treat cancer. These medicines can sometimes cause problems in the stomach and liver when used in combination with other cancer treatments, which can lead to hospitalization or, rarely, death. We performed a study on 6581 people who took these medicines in combination with another treatment and determined exactly how often these side effects happened. We also looked at which combinations of medicines were safer. This information can help doctors identify the side effects early and treat them. It can also help scientists design more studies to learn more about these side effects and how to prevent them.

Checkpoint inhibitor-based salvage regimens prior to autologous stem cell transplant improve event-free survival in relapsed/refractory classic Hodgkin lymphoma.

Clinical trials of novel salvage therapies have encouraging outcomes for relapsed/refractory transplant-eligible classic Hodgkin lymphoma (R/R cHL) but comparison with conventional chemotherapy is lacking. Herein, we report the final analysis of a multicenter retrospective cohort of R/R cHL assessing outcomes by type of salvage therapy before autologous stem cell transplant (ASCT). R/R cHL patients who underwent ASCT at 14 institutions across the United States were included. Outcomes were compared among patients receiving conventional chemotherapy, brentuximab vedotin (BV) + chemotherapy, BV alone, and a checkpoint inhibitor (CPI)-based regimens before ASCT. Study endpoints included event-free survival (EFS), progression-free survival (PFS), and overall survival (OS). All endpoints are defined from relapse. Of 936 patients, 728 received conventional chemotherapy, 73 received BV + chemotherapy, 70 received BV alone, and 65 received CPI-based regimens prior to ASCT. When adjusted for time to relapse, pre-ASCT response and use of BV maintenance, patients receiving CPI-based regimens had superior 2-year EFS compared to conventional chemotherapy, BV + chemotherapy, and BV alone (79.7, 49.6, 62.3, and 36.9%, respectively, p < .0001). Among 649 patients transplanted after 1 line of salvage therapy, CPI-based regimens were associated with superior 2-year PFS compared to conventional chemotherapy (98% vs. 68.8%, hazard ratio: 0.1, 95% confidence interval: 0.03-0.5, p < .0001). OS did not differ by pre-ASCT salvage regimen. In this large multicenter retrospective study, CPI-based regimens improved EFS and PFS compared to other salvage regimens independent of pre-ASCT response. These data support earlier sequencing of CPI-based regimens in R/R cHL in the pre-ASCT setting.

Review of Mesenteric Ischemia in COVID-19 Patients.

The new coronavirus (COVID-19) infection, first detected in Wuhan, China in 2019 has become a pandemic that has spread to nearly every country in the world. Through October 11, 2021, more than 23 billion confirmed cases and 4.8 million fatalities were reported globally. The bulk of individuals afflicted in India during the first wave were elderly persons. The second wave, however, resulted in more severe diseases and mortality in even younger age groups due to mutations in the wild virus. Symptoms may range from being asymptomatic to fatal acute respiratory distress syndrome (ARDS). In addition to respiratory symptoms, patients may present with gastrointestinal symptoms such as stomach pain, vomiting, loose stools, or mesenteric vein thrombosis. The frequency of patients presenting with thromboembolic symptoms has recently increased. According to certain studies, the prevalence of venous thromboembolism among hospitalized patients ranges from 9 to 25%. It was also shown that the incidence is significantly greater among critically sick patients, with a prevalence of 21-31%. Although the exact origin of thromboembolism is unknown, it is considered to be produced by several altered pathways that manifest as pulmonary embolism, myocardial infarction, stroke, limb gangrene, and acute mesenteric ischemia. Acute mesenteric ischemia (AMI) is becoming an increasingly prevalent cause of acute surgical abdomen in both intensive care unit (ICU) and emergency room (ER) patients. Mesenteric ischemia should be evaluated in situations with unexplained stomach discomfort. In suspected situations, appropriate imaging techniques and early intervention, either non-surgical or surgical, are necessary to avert mortality. The purpose of this article is to look at the data on acute mesenteric ischemia in people infected with COVID-19.

Venetoclax and Hypomethylating Agent Combination in Myeloid Malignancies: Mechanisms of Synergy and Challenges of Resistance.

There has been a widespread adoption of hypomethylating agents (HMA: 5-Azacytidine (5-Aza)/decitabine) and venetoclax (Ven) for the treatment of acute myeloid leukemia (AML); however, the mechanisms behind the combination's synergy are poorly understood. Monotherapy often encounters resistance, leading to suboptimal outcomes; however, the combination of HMA and Ven has demonstrated substantial improvements in treatment responses. This study elucidates multiple synergistic pathways contributing to this enhanced therapeutic effect. Key mechanisms include HMA-mediated downregulation of anti-apoptotic proteins, notably MCL-1, and the priming of cells for Ven through the induction of genes encoding pro-apoptotic proteins such as Noxa. Moreover, Ven induces sensitization to HMA, induces overcoming resistance by inhibiting the DHODH enzyme, and disrupts antioxidant pathways (Nrf2) induced by HMA. The combination further disrupts oxidative phosphorylation in leukemia stem cells, amplifying the therapeutic impact. Remarkably, clinical studies have revealed a favorable response, particularly in patients harboring specific mutations, such as IDH1/2, NPM1, CEBPA, or ASXL1. This prompts future studies to explore the nuanced underpinnings of these synergistic mechanisms in AML patients with these molecular signatures.

Bio-Synthesis of Aspergillus terreus Mediated Gold Nanoparticle: Antimicrobial, Antioxidant, Antifungal and In Vitro Cytotoxicity Studies.

Gold nanoparticles (GNP) were bio-fabricated utilizing the methanolic extract of the endophytic isolate Aspergillus terreus. The biosynthesised gold nanoparticles (GNP023) were characterised using UV-visible spectroscopy (UV-Vis); transmission electron microscopy (TEM), Fourier-transform nfrared spectroscopy (FTIR) and X-ray diffraction (XRD) studies. The bio-fabricated GNP023 displayed a sharp SPR peak at 536 nm, were spherically shaped, and had an average size between 10-16 nm. The EDX profile confirmed the presence of gold (Au), and XRD analysis confirmed the crystalline nature of GNP023. The antimicrobial activity of GNP023 was investigated against several food-borne and phytopathogens, using in vitro antibacterial and antifungal assays. The maximum zone of inhibition was observed for S. aureus and V. cholera at 400 µg /mL, whereas inhibition in radial mycelial growth was observed against Fusarium oxysporum and Rhizoctonia solani at 52.5% and 65.46%, respectively, when challenged with GNP023 (200 µg/mL). Moreover, the gold nanoparticles displayed significant antioxidant activity against the ABTS radical, with an IC50 of 38.61 µg/mL, and were non-toxic when tested against human kidney embryonic 293 (HEK293) cells. Thus, the current work supports the application of myco-synthesised gold nanoparticles as a versatile antimicrobial candidate against food-borne pathogens.

Wearable microfluidic-based e-skin sweat sensors.

Electronic skins (e-skins) are soft (deformable and stretchable) state-of-the-art wearable devices that emulate the attributes of human skin and act as a Human-Machine Interface (HMI). Recent advances in e-skin for real-time detection of medical signals such as pulse, temperature, electromyogram (EMG), electroencephalogram (EEG), electrooculogram (EOG), electrocardiogram (ECG), and other bioelectric signals laid down an intelligent foundation for early prediction and diagnosis of diseases with a motive of reducing the risk of the ailment reaching to the end stage. In particular, sweat testing has been employed in diverse applications ranging from medical diagnosis of diabetes, cystic fibrosis, tuberculosis, blood pressure, and autonomic neuropathy to evaluating fluid and electrolyte balance in athletes. Typically, sweat testing techniques are done by trained experts and require off-body measurements, which prevent individuals from de-coding health issues quickly and independently. With the onset of soft electronics, wearable sweat sensors overcome this disadvantage via in situ sweat measurements with real-time feedback, timely diagnosis, creating the potential for preventive care and treatment. Over the past few decades, wearable microfluidic-based e-skin sweat sensors have paved a new way, promising sensing interfaces that are highly compatible with arranging medical and electronic applications. The present review highlights the recent research carried out in the microfluidic-based wearable sweat sensors with a critical focus on real-time sensing of lactate, chloride, and glucose concentration; sweat rate, simultaneously with pH, and total sweat loss for preventive care, timely diagnosis, and point-of-care health and fitness monitoring.

Characterization of an Endophytic Strain Talaromyces assiutensis, CPEF04 With Evaluation of Production Medium for Extracellular Red Pigments Having Antimicrobial and Anticancer Properties.

Considering the worldwide demand for colorants of natural origin, the utilization of ascomycete fungi as a prolific pigment producer unfolds a novel way to obtain these pigments for various applications, including food, cosmetic, and medical use. The presence of very few natural red pigment alternatives in the market also attracts research and industry priorities to unearth novel and sustainable red pigment producers. The present work is an attempt to identify a novel source of red color obtained from endophytic fungi isolated from terrestrial and marine habitats. Based upon the fungal capacity for pigment production, seven isolates of endophytic fungi were recognized as prospective pigment producers. Out of all, fungal isolate CPE04 was selected based upon its capacity to produce profuse extracellular red pigment. The isolate was identified as Talaromyces assiutensis, employing morphological features and phylogenetic characterization by internal transcribed spacer (ITS) sequences. To understand the chemical behavior of pigment molecules, an investigation of the chemical profile of fungal culture filtrate dried powder (CFDP) was performed using ultra-high-performance liquid chromatography-diode array detector-mass spectrometry (UPLC-DAD-MS). In total, eight compounds having pigment and pharmaceutical application were tentatively identified using UPLC-DAD-MS. Considering the commercial aspect of the stated work, an effort was also made for standardizing the upscaling of the pigment molecule. Investigations were performed for optimum medium and culturing conditions for maximum pigment production. CFDP was found to have a significant antibacterial activity against the bacterial pathogens Staphylococcus aureus (MTCC737), Vibrio cholerae (N16961), and methicillin-resistant S. aureus (MRSA) (ATCC BAA811). The CFDP showed a minimum inhibitory concentration at 64, 128, and 256 µg/ml against S. aureus, MRSA, and V. cholerae. A concentration-dependent (50-400 µg/ml) anticancer effect on HeLa cancer line was also observed, having a half-maximal inhibitory concentration (IC50) at 300 µg/ml. The antioxidant potential of CFDP has also been proven with the help of an antioxidant assay against 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical (IC50, 32.01 µg/ml); DNA nicking assay and reactive oxygen species were generated in HeLa cancer line cells. The CFDP was also found to have no cytotoxicity toward HEK 293 T cell line using alamar blue (resazurin), a cell metabolic activity reagent.

Assessment of Oral Health-Care Needs for Patients under Palliative Care.

BACKGROUND: Patients under palliative care and their caregivers often ignore the dental treatment and oral hygiene needs as a result of which they face many day to day problems, which include difficulty in chewing, halitosis, and dry mouth eventually deteriorating the quality of life. OBJECTIVE: The aim of this study is to understand the oral needs and oral health-related concerns of the patients under palliative care. METHODOLOGY: A total of eight patients agreed to enroll in the study. A detailed interview with oral examination, including Sillness and Loe Plaque Index and Decayed Missing and Filled Teeth (dmft) Index, was recorded. Patients were also given the treatment needed if willing for the same. RESULTS: In our study, we observed that the mean dmft scores of dentulous patients were 7.96 ± 3.35, and mean plaque score was 1.75 ± 2.12, which was significantly higher and further highlights the need for dental treatment. CONCLUSION: The patients under palliative care have many oral problems such as dry mouth, difficulty in eating, halitosis which needs to be addressed; hence, dental health plays an important role in improving the quality of life of these patients.

Calcifying epithelial odontogenic tumors (Pindborg tumor) of maxilla in pediatric patients.

The calcifying epithelial odontogenic tumor (CEOT) was first described by Pindborg as a distinct entity in 1955. Odontogenic tumors are derived from epithelial, ectomesenchymal, and/or mesenchymal elements that are or have been a part of the tooth-forming apparatus. Of all the odontogenic tumors, CEOT accounts for 1% of the cases. There is no sex predilection, with a 2:1 predilection for the mandible, mostly in the premolar/molar region. The CEOT typically presents clinically as an intraosseous, expansile, and painless mass that exhibits slow growth. It is often locally invasive. Most often, it is associated with an impacted tooth, is asymptomatic, and requires biopsy for diagnosis. Although most of these cases are primarily intraosseous, an extraosseous tumor is also known to occur, first observed by Pindborg in 1966. The lesions were surgically enucleated, and histopathological examination confirmed CEOT. The purpose of this article is to describe one additional case of both variants of CEOT.

A rare case report of large B cell lymphoma in adult presentation as intussusception.

Adult intussusception represents 5% of all intussusceptions. Primary gastro-intestinal lymphoma comprises 1%-4% of all gastro- intestinal malignancies 90% of them are B-cell non-Hodgkin's lymphoma (NHL). Most common NHL is diffuse large B-cell lymphoma accounts for 30-40%. Most common lymphoma causing intussusception is diffuse large B-cell lymphoma (DLBCL). We herein report a rare case of ileo-colic intussusception due to DLBCL in a 50- years-old male. Computed tomography showed ileo-colic intussusception with possibility of neoplastic etiology as a lead point. Hemicolectomy with ileo-colic anastomosis was done laparoscopically with post-operative chemotherapy. Subsequently, whole body positron emission tomography-computed tomography verified complete resolution of the malignancy. This study aims to present a rare case of ileo-colic intussusception due to non- Hodgkin's B-cell lymphoma in a patient with unusual clinical course and highlight the importance of not only the timely surgical intervention but also the significance of strict adherence to follow up and chemotherapy will completely eradicate the malignancy.

Rhinovirus-induces progression of lung disease in a mouse model of COPD via IL-33/ST2 signaling axis.

Rhinovirus (RV), which is associated with acute exacerbations, also causes persistent lung inflammation in patients with chronic obstructive pulmonary disease (COPD), but the underlying mechanisms are not well-known. Recently, we demonstrated that RV causes persistent lung inflammation with accumulation of a subset of macrophages (CD11b+/CD11c+), and CD8+ T cells, and progression of emphysema. In the present study, we examined the mechanisms underlying the RV-induced persistent inflammation and progression of emphysema in mice with COPD phenotype. Our results demonstrate that at 14 days post-RV infection, in addition to sustained increase in CCL3, CXCL-10 and IFN-γ expression as previously observed, levels of interleukin-33 (IL-33), a ligand for ST2 receptor, and matrix metalloproteinase (MMP)12 are also elevated in mice with COPD phenotype, but not in normal mice. Further, MMP12 was primarily expressed in CD11b+/CD11c+ macrophages. Neutralization of ST2, reduced the expression of CXCL-10 and IFN-γ and attenuated accumulation of CD11b+/CD11c+ macrophages, neutrophils and CD8+ T cells in COPD mice. Neutralization of IFN-γ, or ST2 attenuated MMP12 expression and prevented progression of emphysema in these mice. Taken together, our results indicate that RV may stimulate expression of CXCL-10 and IFN-γ via activation of ST2/IL-33 signaling axis, which in turn promote accumulation of CD11b+/CD11c+ macrophages and CD8+ T cells. Furthermore, RV-induced IFN-γ stimulates MMP12 expression particularly in CD11b+/CD11c+ macrophages, which may degrade alveolar walls thus leading to progression of emphysema in these mice. In conclusion, our data suggest an important role for ST2/IL-33 signaling axis in RV-induced pathological changes in COPD mice.

Enhancing the effectiveness of zinc, cadmium, and lead phytoextraction in polluted soils by using amendments and microorganisms.

For remediating polluted soils, phytoextraction of metals received considerable attention in recent years, although slow removal of metals remained a major constraint in this approach. We, therefore, studied the effect of selected organic and inorganic amendments on the solubility of zinc (Zn), cadmium (Cd), and lead (Pb) in polluted soil and enhancing the efficacy of phytoextraction of these metals by Indian mustard (Brassica juncea cv. Pusa Vijay). For this purpose, a greenhouse experiment was conducted using a metal-polluted soil to evaluate the effect of amendments, viz. green manure (T2), EDTA (T3), sulfur (S)+S oxidizing bacteria (Thiobacillus spp.) (T4), metal-solubilizing bacteria (Pseudomonas spp.) (T5), and green manure + metal-solubilizing bacteria (T6), on solubility and bioavailability of Zn, Cd, and Pb. Distribution of metals in different soil fractions revealed that Cd content in water soluble + exchangeable fraction increased to the extent of 34.1, 523, 133, 123, and 75.8% in T2, T3, T4, T5, and T6 treatments, respectively, over control (T1). Cadmium concentrations in soil solution as extracted by Rhizon sampler were recorded as 3.78, 88.1, 11.2, 6.29, and 4.27 µg L-1in T2, T3, T4, T5, and T6, respectively, whereas soil solution concentration of Cd in T1 was 0.99 µg L-1. Activities of Cd (pCd2+) in Baker soil extract were 12.2, 10.9, 6.72, 7.74, 7.67, and 7.05 for T1, T2, T3, T4, T5, and T6, respectively. Cadmium contents in shoot were recorded as 2.74, 3.12, 4.03, 4.55, 4.68, and 4.63 mg kg-1 in T1, T2, T3, T4, T5, and T6 treatments, respectively. Similar trend in Zn and Pb content with different magnitude was also observed across the different amendments. Cadmium uptake by shoot of mustard was enhanced to the extent of 125, 62.5, 175, 175, and 212% grown on T2-, T3-, T4-, T5-, and T6-treated soil, respectively, over T1. By and large, free ion activity of metals as measured by Baker soil test proved to be the most effective index for predicting Zn, Cd, and Pb content in shoot of mustard, followed by EDTA and DTPA. Among the metal fractions, only water soluble + exchangeable metal contributed positively towards plant uptake, which explained the variation in shoot Zn, Cd, and Pb content to the extent of 74, 81, and 87%, respectively, along with other soil metal fractions. Risk to human health for intake of metals through the consumption of leafy vegetable (mustard) grown on polluted soil in terms of hazard quotient (HQ) ranged from 0.64 to 1.10 for Cd and 0.11 to 0.34 for Pb, thus rendering mustard unfit for the human consumption. Novelty of the study mainly consisted of the use of natural means and microorganisms for enhancing solubility of metals in soil with the ultimate aim of hastening the phytoremediation.

NOTCH3 contributes to rhinovirus-induced goblet cell hyperplasia in COPD airway epithelial cells.

RATIONALE: Goblet cell hyperplasia (GCH) is one of the cardinal features of chronic obstructive pulmonary disease (COPD) and contributes to airways obstruction. Rhinovirus (RV), which causes acute exacerbations in patients with COPD, also causes prolonged airways obstruction. Previously, we showed that RV enhances mucin gene expression and increases goblet cell number in a COPD mouse model. This study examines whether RV causes sustained GCH in relevant models of COPD. METHODS: Mucociliary-differentiated COPD and normal airway epithelial cell cultures and mice with normal or COPD phenotype were infected with RV or sham and examined for GCH by immunofluorescence and/or mucin gene expression. In some experiments, RV-infected COPD cells and mice with COPD phenotype were treated with γ-secretase inhibitor or interleukin-13 neutralising antibody and assessed for GCH. To determine the contribution of NOTCH1/3 in RV-induced GCH, COPD cells transduced with NOTCH1/3 shRNA were used. RESULTS: RV-infected COPD, but not normal cell cultures, showed sustained GCH and increased mucin genes expression. Microarray analysis indicated increased expression of NOTCH1, NOTCH3 and HEY1 only in RV-infected COPD cells. Blocking NOTCH3, but not NOTCH1, attenuated RV-induced GCH in vitro. Inhibition of NOTCH signalling by γ-secretase inhibitor, but not neutralising antibody to IL-13, abrogated RV-induced GCH and mucin gene expression. CONCLUSIONS: RV induces sustained GCH via NOTCH3 particularly in COPD cells or mice with COPD phenotype. This may be one of the mechanisms that may contribute to RV-induced prolonged airways obstruction in COPD.