Liver autotransplantation and atrial reconstruction on a patient with multiorgan alveolar echinococcosis: a case report.

BACKGROUND: Alveolar echinococcosis (AE) primarily affects the liver and potentially spreads to other organs. Managing recurrent AE poses significant challenges, especially when it involves critical structures and multiple major organs. CASE PRESENTATION: We present a case of a 59-year-old female with recurrent AE affecting the liver, heart, and lungs following two previous hepatectomies, the hepatic lesions persisted, adhering to major veins, and imaging revealed additional diaphragmatic, cardiac, and pulmonary involvement. The ex vivo liver resection and autotransplantation (ELRA), first in human combined with right atrium (RA) reconstruction were performed utilizing cardiopulmonary bypass, and repairs of the pericardium and diaphragm. This approach aimed to offer a potentially curative solution for lesions previously considered inoperable without requiring a donor organ or immunosuppressants. The patient encountered multiple serious complications, including atrial fibrillation, deteriorated liver function, severe pulmonary infection, respiratory failure, and acute kidney injury (AKI). These complications necessitated intensive intraoperative and postoperative care, emphasizing the need for a comprehensive management strategy in such complicated high-risk surgeries. CONCLUSIONS: The multidisciplinary collaboration in this case proved effective and yielded significant therapeutic outcomes for a rare case of advanced hepatic, cardiac, and pulmonary AE. The combined approach of ELRA and RA reconstruction under extracorporeal circulation demonstrated distinct advantages of ELRA in treating complex HAE. Meanwhile, assessing diaphragm function during the perioperative period, especially in patients at high risk of developing pulmonary complications and undergoing diaphragmectomy is vital to promote optimal postoperative recovery. For multi-resistant infection, it is imperative to take all possible measures to mitigate the risk of AKI if vancomycin administration is deemed necessary.

Withaferin A alleviates inflammation in animal models of arthritis by inhibiting the NF-κB pathway and cytokine release.

Withaferin A, a steroid lactone from Withania somnifera, exhibits anti-inflammatory, immunomodulatory, and antioxidant properties. This study investigated the effects of withaferin A on collagen-induced arthritis (CIA) rats, focusing on NF-κB p65 regulation and cytokine release. Withaferin A (50 mg/kg b.wt., orally) or methotrexate (0.25 mg/kg b.wt., i.p., as a reference drug) was given to CIA rats daily for 20 days postarthritis induction. Joints were removed from nonarthritic and arthritic rats to assess the levels of NO, MPO, interleukin (IL)-1ß, IL-6, IL-10, TNF-α, COX-2, and NF-κB via ELISA. Furthermore, the mRNA expression of IL-1ß, IL-10, TNF-α, COX-2, iNOS, and NF-κB was also assessed through qPCR. Treatment with withaferin A significantly inhibited the levels of inflammatory cytokines and the transcription factor NF-κB; suppressed the expression of IL-1ß, IL-10, TNF-α, COX-2, iNOS, and NF-κB in the joint tissue of CIA rats; and reduced cartilage and bone destruction, as shown by H&E staining. To confirm the results obtained from biochemical and molecular studies and to determine the molecular target of withaferin A, we performed a molecular simulation of the potential targets of withaferin A, which identified the NF-κB pathway as its target. These results suggested that withaferin A effectively attenuated rheumatoid arthritis progression by inhibiting the activation of the NF-κB pathway and the downstream secretion of inflammatory cytokines.

Outcomes of Surgical Repair of Tetralogy of Fallot: A Comparison Between the Adult and Pediatric Population.

Introduction Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Early detection and timely treatment have provided successful repair of the anomaly in the developed world. However, in the developing world, there is still a burden of uncorrected TOF patients reaching adulthood. The goal of this study is to determine whether there is any difference in postoperative complications between adult and pediatric populations following surgical correction for TOF. Methods This study involved all those patients who received primary or secondary surgical repair for TOF in our facility between January 2017 and December 2020. The patients were split according to their age into the pediatric group if they were under 18 years and the adult group if they were 18 years or older. Patients with absent pulmonary valve or pulmonary atresia were not included in this study. Patients with large major aortopulmonary collateral arteries (MAPCA) were also excluded from this study. All patients underwent total correction through a median sternotomy approach. The ventricular septal defect was closed with a Bard knitted fiber patch. The right ventricular outflow tract (RVOT) was augmented by excising muscle bands or fibrous bands in the RVOT. If the annulus was smaller than the 3.5 z score, then a transannular patch was done using an autologous pericardium. The main pulmonary artery was augmented in every surgery using an autologous pericardial patch. All patients were shifted to the ICU on the ventilator and were extubated after fulfillment of the extubation criteria. Postoperative complications measured included re-opening, re-intubation, prolonged ventilation (>24 hours), and mortality within the index hospital admission. The clinical data of all patients were prospectively collected and analyzed using the chi-square test and t-test. A p-value of less than or equal to 0.05 was considered significant. Results The total number of patients was 134. This included 83 males (60.1%). A total of 114 patients who were aged below 18 years were included in the pediatric group, and 20 patients aged equal to or more than 18 years were included in the adult group. The mean average perfusion time in minutes in the adult group was 125.8 and in the pediatric group, it was 98.79. Similarly, the mean average of the cross-clamp time was also longer in the adult group at 89.55 minutes versus 69.63 minutes in the pediatric group. Overall, in the adult group, three (15%) patients had postoperative complications, while in the pediatric group, a total of 14 (11.9%) patients had postoperative complications (p = 0.001). However, there was no significant difference in the number of re-openings (8.5% vs. 10%; p = 0.8). The total mortality observed was 16 (11.59%). This included 14 (11.9%) in the pediatric group and two (10%) in the adult group. There was no significant difference between the two groups (p = 0.8). Conclusions Surgical repair of TOF can be performed in both adult and pediatric populations with acceptable outcomes. The mortality rate was found to be slightly greater in the pediatric population compared to the adults. However, it can be seen that the number of postoperative complications is greater in adults. Further research is needed to optimize outcomes for both pediatric and adult patients with TOF.

The LDL receptor is regulated by membrane cholesterol as revealed by fluorescence fluctuation analysis.

Membrane cholesterol-rich domains have been shown to be important for regulating a range of membrane protein activities. Low-density lipoprotein receptor (LDLR)-mediated internalization of cholesterol-rich LDL particles is tightly regulated by feedback mechanisms involving intracellular sterol sensors. Since LDLR plays a role in maintaining cellular cholesterol homeostasis, we explore the role that membrane domains may have in regulating LDLR activity. We expressed a fluorescent LDLR-mEGFP construct in HEK293T cells and imaged the unligated receptor or bound to an LDL/DiI fluorescent ligand using total internal reflection fluorescence microscopy. We studied the receptor's spatiotemporal dynamics using fluorescence fluctuation analysis methods. Image cross correlation spectroscopy reveals a lower LDL-to-LDLR binding fraction when membrane cholesterol concentrations are augmented using cholesterol esterase, and a higher binding fraction when the cells are treated with methyl-ß-cyclodextrin) to lower membrane cholesterol. This suggests that LDLR's ability to metabolize LDL particles is negatively correlated to membrane cholesterol concentrations. We then tested if a change in activity is accompanied by a change in membrane localization. Image mean-square displacement analysis reveals that unligated LDLR-mEGFP and ligated LDLR-mEGFP/LDL-DiI constructs are transiently confined on the cell membrane, and the size of their confinement domains increases with augmented cholesterol concentrations. Receptor diffusion within the domains and their domain-escape probabilities decrease upon treatment with methyl-ß-cyclodextrin, consistent with a change in receptor populations to more confined domains, likely clathrin-coated pits. We propose a feedback model to account for regulation of LDLR within the cell membrane: when membrane cholesterol concentrations are high, LDLR is sequestered in cholesterol-rich domains. These LDLR populations are attenuated in their efficacy to bind and internalize LDL. However, when membrane cholesterol levels drop, LDL has a higher binding affinity to its receptor and the LDLR transits to nascent clathrin-coated domains, where it diffuses at a slower rate while awaiting internalization.

Ocimum sanctum L water extract: In-situ green synthesis of zinc oxide nanoparticles for treatment of rheumatoid arthritis: Preclinical study.

BACKGROUND AND OBJECTIVE: Rheumatoid arthritis is a chronic progressive autoimmune disorder, characterised by destruction of cartilage and under line bones. Though exact etiology of rheumatoid arthritis (RA) remains unknown. It is believed that alteration in control of cellular or molecular responses is involved in the chronic inflammation. Earlier in RA patients it was observed the circulating RA specific biomarkers and immunoglobulin deposits in the synovial joints. Zinc Oxide Nanoparticles (ZnO NPs) is used as an anti-inflammatory and anticancer agent, however there is nil/very less scientific data shows the anti-arthritic activity of green synthesis ZnO nanoparticles (Ocimum sanctum water extract in-situ synthesis of ZnO NPs having active compound Caffeic acid and Rosmerinic acid). Hence, the present activity was planned to assess the anti-arthritic activity of ZnO NPs in CIA rats. METHODS: Arthritis in rats were induced by subcutaneous injection of collagen type II (CII) (200 µl) at the base of tail on day 0 followed by booster dose on day 14. ZnO NPs were given (2 mg/kg b.wt./day) orally for 20 days. At the end of the study serum, joint homogenate was used to assess the level of biomarkers (RF, a-CCP, a-CII and CRP) and inflammatory mediators. In addition, m-RNA expression of various genes such as Nuclear factor-kB (NF-kB), inflammatory mediators like tumour necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) etc. were assayed in joint tissue. Finally all these biochemical and molecular results were confirmed by microscopic study of joint tissue. RESULTS: ZnO NPs, treated rats showed decrease in inflammation and clinical severity. This was related with decrease in the level of biomarkers (like RF, a-CCP and CRP), inflammatory mediators (TNF-α, COX-2) and activity of transcription factor NF-kB. All these findings were positively correlated with microscopic analysis of joint tissue that showed reduced inflammation and bone erosion in treated group. CONCLUSION: This study validates the anti-arthritic activity of ZnO NPs as it mitigates the arthritis related symptoms in CIA rats.

Breastfeeding practices in nursing mothers during COVID-19 pandemic: Dual center study in Karachi, Pakistan.

Objective: To identify the breastfeeding practices in nursing mothers during the COVID-19 pandemic. Methods: This descriptive cross-sectional study was conducted in the Pediatrics and Gynecology & Obstetrics departments at two of the tertiary care hospitals in Pakistan from September 2020 to February 2021. Recently delivered mothers and mothers of children till two years of age on breastfeeding/formula feed were consecutively enrolled. Result: Of 484 participants, breastfeeding was practiced by 180 (37.2%) participants, formula-fed by 85 (17.6%), and mix feed by 219 (45.2%) participants. Out of 185 mothers who had to breastfeed previous babies, 80.2% of mothers still opted to breastfeed their newborns despite the COVID-19 pandemic. Breastfeeding practices exhibited higher incidence in illiterate mothers (aOR 0.229 95% CI 0.05-0.95, p- 0.042), housewives (aOR 0.35 95% CI 0.13-0.95 p-0.040) and shorter length of stay (aOR 0.290 95% CI 0.15-0.57, p- 0.001) while formula /mixed feeding was found higher in mothers with exposure to formula feeding in previous babies (aOR 17.842, 95% CI 8.33-38.19, p- 0.001) and mothers with pain after delivery (aOR 4.526, 95% CI 2.11-9.71, p-<0.001). Conclusion: Mothers who had to breastfeed their babies in a previous pregnancy, who were less educated, and housewives with a shorter stay in hospital have shown a stronger association with breastfeeding whereas mothers who had previous exposure to formula milk and pain after delivery have shown association to formula feed or mixed feed.

Understanding the dynamics of capital structure, corporate governance, and corporate social responsibility in high- and low-leveraged US and Chinese firms.

Corporate social responsibility turned into a global sensation from the inception of the twenty-first century in the corporate world and grabbed immense engrossment from all stakeholders in their decision-making process. Capital structure and corporate governance practices are the well-mellowed facets of corporate finance literature. In this study, the moderating role of corporate social responsibility (CSR) between corporate governance and leverage of the US and Chinese listed firms has been established, with a further extension of analyzing the moderating role of CSR between corporate governance and leverage in high vs low leveraged firms and high CSR vs low CSR firms as the novelty of this study and has never been examined in both economies and globally. The data of 1989 Chinese-listed firms from 28 sectors of the economy and 6640 US-listed firms from 27 sectors of the economy has been taken from 2001 to 2019 and analyzed through fixed effect regression and system generalized method of moment (GMM). Results of the study reveal that CSR and corporate governance are negatively associated with the leverage of both Chinese and US firms. Moreover, the moderating role of CSR has established between corporate governance and leverage negative relationship. The moderating role of CSR in the relationship of leverage and corporate governance is established only in low-leveraged firms whereas it is insignificant in high-leveraged firms. System GMM confirms the signs and significance of the regression results; that is why regression results are robust and reliable, and there is no endogeneity problem in our model. The study also gives an insight for future research on high- and low-leveraged firms and firms with more CSR score than less CSR score with other dimensions such as firm performance and firm value variables.

Divulging the Intricacies of Crosstalk Between NF-kB and Nrf-2/Keap1 Pathway in the Treatment of Arthritis by Dimethyl Fumarate.

The aim of this study was to examine the hypothesis that use of dimethyl fumarate (DMF) may mitigate arthritic symptoms in collagen-induced arthritis (CIA) rats through activation of NF-E2-related factor 2(Nrf-2) and suppression of NF-kB pathway. Arthritis in rats was induced by subcutaneous injection of collagen type II (200 µl) at the base of the tail. After induction arthritic rats were treated with DMF (25 mg/kg b.wt.) for 20 days from the day 25th to 45th. At the end of the study, serum and joint homogenate was used to assess the oxidative stress and cytokines level. In addition, mRNA expression of various genes such as NF-kB, Keap-1 (Kelch-like ECH-associated protein 1) and Nrf-2 was assayed through qRT-PCR in joint tissue. Finally, all these biochemical and molecular results were confirmed by histological and in silico study. Our results showed that decrease in the clinical severity, inflammation, and cell necrosis in DMF-treated rats. This was related with decrease in NF-kB activity and increase in activity of Nrf-2. Treatment with DMF increases the levels of endogenous antioxidant biomarkers glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) and decreases inflammation. These biochemical and molecular results were further confirmed by performing in silico study that shows DMF strongly inhibits the activation of NF-kB, and conversely at the same time increases the activity of Nrf-2 that means a significantly lower amount of inflammatory mediators and oxidants was produced. Decrease in inflammation leads to preserving the joint architecture and alleviation from clinical symptoms of arthritis. Collectively, these results indicate that Nrf-2 activation protects against arthritic symptoms.

Assessment of the influence of metal ions released from the fixed orthodontic appliances on the static friction and surface topography of stainless steel and I archwires: An in-vitro study.

BACKGROUND: Static friction force between the orthodontic brackets and wire impacts the sliding mechanics that affect teeth movements and treatment duration. This sliding media is jam-packed with released metal ions from the fixed appliances. This study aimed to assess the static frictional force and surface topography of stainless steel (SS) and I archwires in dry conditions and in media fully with metal ions that were released from fixed appliances. METHODS: In this research study, a set of 60 as-received straight archwires specimens (5 cm wire) were employed and categorized into two groups based on the material type [30 super elastics new I archwires gauge (0.018 × 0.014 inch) and 30 SS archwires 0.018 × 0.022" as a control]. The archwires' static friction force was measured while sliding a loaded Roth SS brackets (0.018") on the archwire using a universal tensile testing machine in dry and metal ions released media, while the surface topography was assessed using a noncontact AFM machine. RESULTS: The static friction of I archwire was significantly lower than the SS wire in dry condition. Metal ions media released from fixed appliances significantly reduced the Static friction compared to dry and wet conditions with deionized water for both wires. An Atomic Force Microscope machine surface roughness reports revealed that the highest mean of all three roughness parameters was found in the SS group, followed by I archwires in descending order. Additionally, metal ions media significantly reduce all roughness parameters.

Ellagic acid protects type II collagen induced arthritis in rat via diminution of IKB phosphorylation and suppression IKB-NF-kB complex activation: in vivo and in silico study.

OBJECTIVE: The present study was designed to explore the potential anti-inflammatory and anti-arthritic effects of ellagic acid (EA) in collagen-induced arthritis (CIA). METHODS: CIA rats were treated with MTX (0.25 mg/kg body wt.) and EA (50 mg/kg b.wt.) for a period of 20 days. The effects of treatment in the rats were assessed biochemically by analyzing inflammatory mediators (NF-kB, iNOS, TNF-α, IL-1ß, IL-6 and IL-10) and oxidative stress related parameters (MPO, NO, LPO, catalase, SOD, GSH). In addition, we also assessed the expression of some inflammatory mediators TNF-α, CD8 + though immunohistochemistry in the joint tissue. RESULTS: In the present study, we found expression and synthesis of transcription factor NF-kB was prominent in CIA rats. In addition, main pro-inflammatory cytokines such as TNF-α, IL-1ß, IL-6, and the anti-inflammatory IL-10, was also stand out. Further, reactive oxygen/nitrogen species was also elevated in CIA rats. Treatment with EA ameliorates all the above mentioned inflammatory and oxidative stress related parameters to near normal. Further, we also confirmed the expression of TNF-α, CD8+ T cells through immunohistochemistry was mitigates in joint tissue of EA treated rats. We find EA significantly inhibited the developmental phase of arthritis. CONCLUSION: These results suggest that EA act as potent anti-arthritic and anti-inflammatory agent that could be used as a tool for the development of new drug for the treatment of arthritis.

Isolation of a Novel Endophytic Bacillus Strain Capable of Transforming Pentachlorophenol and Structure Determination of Pentachlorophenol Phosphate Using Single-Crystal X-ray Diffraction.

A novel approach for the remediation of upland soils contaminated with pentachlorophenol (C6HCl5O; PCP) (1), a fungicide, wood perservative, and herbicide, through the exploitation of plant-endophytic bacteria may overcome the existing issues in bioaugmentaion and phytoremidiation. In this study, we isolated the endophytic Bacillus sp. strain PCP15 and determined its metabolite of PCP (1). This strain degraded 8.03 µmol L-1 PCP (1) within 24 h and generated the novel metabolite PCP phosphate (3). The PCP15 strain showed nearly complete growth inhibition of 20 µmol L-1 PCP (1). In contrast, PCP15 showed resistance to PCP phosphate (3), indicating that the phosphorylation of PCP, which has never previously been reported in organisms, contributed to the detoxification of PCP (1) in bacterial cells. Our results show the potential for practical application of this strain in hybrid remediation of PCP (1)-contaminated soils and reveal a novel PCP (1) detoxification mechanism in organisms.

Inducing Microscale Structural Order in Phage Nanofilament Hydrogels with Globular Proteins.

Biological hydrogels play important physiological roles in the body. These hydrogels often contain ordered subdomains that provide mechanical toughness and other tissue-specific functionality. Filamentous bacteriophages are nanofilaments with a high aspect ratio that can self-assemble into liquid crystalline domains that could be designed to mimic ordered biological hydrogels and can thus find applications in biomedical engineering. We have previously reported hydrogels of pure cross-linked liquid crystalline filamentous phage formed at very high concentrations exhibiting a tightly packed microstructure and high stiffness. In this work, we report a method for inducing self-assembly of filamentous phage into liquid crystalline hydrogels at concentrations that are several orders of magnitude below that of lyotropic liquid crystal formation, thus creating structural order but a less densely packed microstructure. Hybrid hydrogels of M13 phage and bovine serum albumin (0.25 w/v%) were formed and shown to adsorb up to 16× their weight in water. Neither component gelled on its own at the low concentrations used, suggesting synergistic action between the two components in the formation of the hydrogel. The hybrid hydrogels exhibited repetitive self-healing under physiological conditions and at room temperature, autofluorescence in three channels, and antibacterial activity toward Escherichia coli host cells. Furthermore, the hybrid hydrogels exhibited a more than 2× higher ability to pack water compared to BSA-only hydrogels and 2× lower compression modulus compared to tightly packed M13-only hydrogels, suggesting that our method could be used to create hydrogels with tunable mechanical properties and pore structure through the addition of globular proteins, while maintaining bioactivity and microscale structural order.

AN OVERVIEW OF AUTOIMMUNITY IN IMPLANTATION FAILURE: A LITERATURE REVIEW.

OBJECTIVE: The aim: This review was aimed to understand the role of different types of autoantibodies like antiphospholipid, antithyroid, antisperm, antinuclear, anti-ovarian autoantibodiesand heat shock protein HSP 60 in the process of implantation in the normal way of conceiving and IVF and also to estimate that how the presence of these autoantibodies affect the normal pregnancy outcome. PATIENTS AND METHODS: Materials and methods: This review process performed in the obstetrics and gynaecology postgraduate department, Bogomolets national medical university, Kyiv, Ukraine. It was a review of already published papers not to need the ethical board committee's approval. By following the literature review guidelines, this paper was written and searched for relevant studies regarding autoantibodies and implantation, published in medical literature till 2020 were included in this review process. The search is done for studies published till 2020 in the English language from the Medline database, including Google Scholar, PubMed, Web of Science and Cochrane library database. CONCLUSION: Conclusions: Our recent work found that the involvement of APA, ANA and/or ATA in recipients of oocyte donations did not affect their pregnancy outcomes. Some researchers did not give any clear conclusion about these risks, and some stated that the use of some immunodepressant agents could be useful to reduce the harmful effects of these autoantibodies associated with implantation failure. Each autoantibody has a different mechanism of action to create the pathological state, some have direct effect, and some indirectly impact implantation. In future, further high-quality studies need to be performed for better understanding.

A PROSPECTIVE STUDY TO ANALYZE THE SPECIFICITY OF CHLAMYDIAL HEAT SHOCK PROTEIN (CHSP60) ANTIBODIES TO DIAGNOSE TUBAL INFERTILITY.

OBJECTIVE: The aim: To investigate the utility of testing for chlamydial heat shock protein 60 (CHSP60) antibodies in the diagnosis of tubal infertility. PATIENTS AND METHODS: Materials and methods: All the collected samples were assayed for IgM and IgG antibodies to chlamydia trachomatis and chlamydial heat shock protein 60 (CHSP60) by using immunofluorescence and enzyme-linked immunosorbent assay (ELISA) techniques, respectively. RESULTS: Results: There were no substantial differences between antibodies to C. trachomatis in females with tubal infertility (67%) and non-tubal infertility (48%). However, women with tubal infertility (45%) have more anti-CHSP60 antibodies than non-tubal infertility (9%). Antibody screening for C. trachomatis has only (63%) sensitivity and (54%) specificity for detecting tubal infertility. On the other hand, the CHSP60 antibody testing has (44%) sensitivity and 92% specificity for diagnosing tubal infertility. A positive microimmunofluorescence (MIF) titer was observed in 12 of 18 (67%) females with the tubal problem, 31 of 64 (48%) with non-tubal infertility (P=0.3, OR=2.2, 95% CI=0.71 to 8.01). The CHSP60 antibodies were found in 8 of 18 (45%) females with tubal problem & 6 of 64 (9%) women with non-tubal infertility, power factor alpha α P=0.004, OR=9.3, 95% CI=2.1 to 43.2, power= 1.002 for n= 0.05). Incorporating CHSP60 and C. trachomatis antibodies testing gives an excellent positive probability proportion of 10 to diagnose C. trachomatis associated tubal infertility. CONCLUSION: Conclusions: CHSP60 antibody testing is a more specific evaluation than antibody testing for C. trachomatis for predicting chlamydia-associated tubal infertility. Using these tests at the first infertility examination may help the immediate diagnosis for non-interceptive tubal infertility.

Non-target Impact of Dinotefuran and Azoxystrobin on Soil Bacterial Community and Nitrification.

Pesticides to protect crops from pests are subject to rigorous risk assessment before registration in Japan. However, further information needs to be collected regarding the assessment of impacts on the natural environment. In particular, nitrifying bacteria play a role in converting ammonium salts to nitrates in soil. However, there is limited research covering the effects of insecticides on nitrification, despite several fungicides and herbicides have an inhibitory effect on nitrifying bacteria. Therefore, we investigated the effect of pesticides on the nitrification when applied to soil. The application of both pesticides promoted ammonia oxidation, and suppressed nitrite oxidation in a high-concentration treatment of dinotefuran. In addition, it was clarified that the diversity and species richness of soil bacteria was significantly reduced when the pesticides were applied to the soil, and that the specific soil bacteria (Metyhlotenera spp.) dominated the application of the pesticides.

Zinc Oxide Nanoparticle Induces Apoptosis in Human Epidermoid Carcinoma Cells Through Reactive Oxygen Species and DNA Degradation.

Zinc oxide nanoparticles (ZnO-NPs) are used immensely in technology and medicine, but very less is known about toxicity mechanism to human epidermal cells. The objective of this study was to evaluate possible anticancer properties of ZnO-NPs on human epidermoid carcinoma cells using MTT assay, measurement of reactive oxygen species, DNA fragmentation, and nuclear condensation. ZnO-NPs were synthesized by sol-gel method using zinc acetate dihydrate, ethylene glycol, and 2-propyl alcohol. Numerous characterization techniques such as UV-visible spectroscopy, X-ray powder diffraction, transmission electron microscopy, and dynamic light scattering spectroscopy were used to confirm synthesis, purity, optical, and surface characteristics, size, shape, and distribution of ZnO-NPs. Our finding showed that ZnO-NPs considerably decreased cell viability of human epidermoid carcinoma A431 cells with a parallel increase in nuclear condensation and DNA fragmentation in a dose dependent manner. Moreover, real time PCR expression study showed that treatment of human epidermoid carcinoma cells with ZnO-NPs trigger increased expression of tumor suppressor gene p53, bax, and caspase-3 while downregulate antiapoptotic gene bcl-2. Thus ZnO-NPs induce apoptosis in A431 cells through DNA degradation and generation of reactive oxygen species via p53, bax/bcl-2, and caspase pathways.

Metabolite profiling reveals a complex response of plants to application of plant growth-promoting endophytic bacteria.

Endophytic bacteria have been explored for their role in plant growth promotion, however, not much has been explored in cucumber. The metabolomic response of plants to application of such microbes also remains largely unknown. Thus, we investigated the application of endophytic bacteria to cucumber to infer their role in plant growth promotion and document metabolome response. The lowest healthy leaf-stalks were sampled from four differently sourced cucumber plants, and endophytic bacteria were isolated after surface disinfection. Initial plant growth-promoting (PGP) screening was performed to identify PGP strains out of numerous isolates, and five strains (Strains 4=Curtobacterium spp., 72=Brevibacillus spp., 167=Paenibacillus spp., 193=Bacillus spp., and 227=Microbacterium spp.) were selected based on their contribution to root growth compared with the control. The selected strains were further evaluated in pot experiments, axenic PGP trait assays, and metabolomic analysis. Results revealed that the selected isolates possessed different qualitative characteristics among indole acetic acid, siderophore production, phosphate solubilization, and 1-aminocyclopropane-1-carboxylate (ACC)-deaminase and nifH genes, and all isolates significantly enhanced plant growth in both pot experiments compared with the uninoculated control and fertilizer control. Metabolomic profiling revealed that both strains affected the plant metabolomes compared with the uninoculated control. Around 50 % of the metabolites explored had higher concentrations in either or both bacteria-applied plants compared with the uninoculated control. Differences were observed in both strains' regulation of metabolites, although both enhanced root growth near equally. Overall, endophytic bacteria significantly enhanced plant growth and tended to produce or induce release of certain metabolites within the plant endosphere.

The effectiveness of a nationwide interactive ECG teaching workshop for UK medical students.

PURPOSE: Interpreting a twelve­lead electrocardiogram (ECG) is a basic, albeit essential skill for most healthcare professionals to attain. Despite its importance, evidence suggests that the competency of healthcare professionals to interpret ECGs can be improved. We evaluated the effectiveness of a national interactive workshop designed to improve ECG interpretation in the UK medical student cohort. METHODS: UK medical students who attended a national workshop were asked to complete a pre- and post- workshop test which comprised of 20 ECGs which showed a variety of pathologies relating to conduction disturbances, tachycardia and acute coronary syndromes. The workshop was interactive and consisted of 6 h of ECG tutorials, divided into hourly sessions which covered all key topics such as 'basic electrophysiology' and 'electro-conduction problems'. Pre- and post-workshop test scores were compared by difference in means using the paired two-tailed t-test. RESULTS: A total of 145 participants completed the pre-test and of those 44 completed both the pre and post-test. The mean pre-test and post-test scores were 9.7/20 questions (48.9%) and 11.2/20 questions (56.2%) respectively, with a mean improvement of 1.5/20 (7.3%) from pre- to post-test (+7.3%, 95% CI: +1.8 to +12.8%, p = 0.01). CONCLUSION: A national ECG workshop which emphasizes activity-based learning may be effective in improving the competency of medical students to interpret ECGs. Further exploration with multi-center controlled studies involving a diverse cohort of students and analyses to determine their cost-effectiveness is warranted.

Randomized Trial of Standard Adjuvant Chemotherapy Regimens Versus Capecitabine in Older Women With Early Breast Cancer: 10-Year Update of the CALGB 49907 Trial.

PURPOSE: Older women with breast cancer remain under-represented in clinical trials. The Cancer and Leukemia Group B 49907 trial focused on women age 65 years and older. We previously reported the primary analysis after a median follow-up of 2.4 years. Standard adjuvant chemotherapy showed significant improvements in recurrence-free survival (RFS) and overall survival compared with capecitabine. We now update results at a median follow-up of 11.4 years. PATIENTS AND METHODS: Patients age 65 years or older with early breast cancer were randomly assigned to either standard adjuvant chemotherapy (physician's choice of either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide and doxorubicin) or capecitabine. An adaptive Bayesian design was used to determine sample size and test noninferiority of capecitabine. The primary end point was RFS. RESULTS: The design stopped accrual with 633 patients at its first sample size assessment. RFS remains significantly longer for patients treated with standard chemotherapy. At 10 years, in patients treated with standard chemotherapy versus capecitabine, the RFS rates were 56% and 50%, respectively (hazard ratio [HR], 0.80; P = .03); breast cancer-specific survival rates were 88% and 82%, respectively (HR, 0.62; P = .03); and overall survival rates were 62% and 56%, respectively (HR, 0.84; P = .16). With longer follow-up, standard chemotherapy remains superior to capecitabine among hormone receptor-negative patients (HR, 0.66; P = .02), but not among hormone receptor-positive patients (HR, 0.89; P = .43). Overall, 43.9% of patients have died (13.1% from breast cancer, 16.4% from causes other than breast cancer, and 14.1% from unknown causes). Second nonbreast cancers occurred in 14.1% of patients. CONCLUSION: With longer follow-up, RFS remains superior for standard adjuvant chemotherapy versus capecitabine, especially in patients with hormone receptor-negative disease. Competing risks in this older population dilute overall survival benefits.