A perspective on the role of uncertainty in sustainability science and engineering.

The Trans-Atlantic Research and Development Interchange on Sustainability Workshop (TARDIS) is a meeting on scientific topics related to sustainability. The 2019 workshop theme was "On the Role of Uncertainty in Managing the Earth for Global Sustainability." This paper presents the perspectives on this topic derived from talks and discussions at the 2019 TARDIS workshop. There are four kinds of uncertainties encountered in sustainability ranging from clear enough futures to true surprises. The current state-of-the-art in assessing and mitigating these uncertainties is discussed.

Pre-discharge postoperative radiographs after primary total knee replacement : tradition or science?

Consistent evidence exists on the inutility of immediate postoperative radiographs after a total knee replacement (TKR). We hypothesized that eliminating the pre-discharge film would not have any effect on the postoperative patient outcomes. Retrospective analysis of prospectively collected data was performed on 220 knees. Patients undergoing a simple primary TKR operated by 2 surgeons (Surgeon A and B) from January 2013 to July 2015 were divided into 2 groups (Groups 1 and 2 having 112 and 108 knees respectively). While Surgeon A routinely asked for the second postoperative day pre-discharge radiograph, Surgeon B directly performed weight bearing radiographs 6 weeks postoperatively. Greater knee pain was seen in Group 1 (p = 0.01). No changes in rehabilitation protocols based on pre-discharge radiographs, complications, medico-legal issues or revision surgery could be identified in any patient. The quality of the pre-discharge radiographs was adequate in 65 of the 112 knees (58%). A cost reduction of approximately $220 per patient was observed with the exclusion of the pre-discharge film. Eliminating routine inpatient pre-discharge radio-graphs after simple primary TKR does not alter the rehabilitation protocol, identify any of the standard complication or have any medico-legal implications. On the contrary, these films seem to increase postoperative pain and costs.

Spatially resolved ultrafast magnetic dynamics initiated at a complex oxide heterointerface.

Static strain in complex oxide heterostructures has been extensively used to engineer electronic and magnetic properties at equilibrium. In the same spirit, deformations of the crystal lattice with light may be used to achieve functional control across heterointerfaces dynamically. Here, by exciting large-amplitude infrared-active vibrations in a LaAlO3 substrate we induce magnetic order melting in a NdNiO3 film across a heterointerface. Femtosecond resonant soft X-ray diffraction is used to determine the spatiotemporal evolution of the magnetic disordering. We observe a magnetic melt front that propagates from the substrate interface into the film, at a speed that suggests electronically driven motion. Light control and ultrafast phase front propagation at heterointerfaces may lead to new opportunities in optomagnetism, for example by driving domain wall motion to transport information across suitably designed devices.

Optical excitation of Josephson plasma solitons in a cuprate superconductor.

Josephson plasma waves are linear electromagnetic modes that propagate along the planes of cuprate superconductors, sustained by interlayer tunnelling supercurrents. For strong electromagnetic fields, as the supercurrents approach the critical value, the electrodynamics become highly nonlinear. Josephson plasma solitons (JPSs) are breather excitations predicted in this regime, bound vortex-antivortex pairs that propagate coherently without dispersion. We experimentally demonstrate the excitation of a JPS in La1.84Sr0.16CuO4, using intense narrowband radiation from an infrared free-electron laser tuned to the 2-THz Josephson plasma resonance. The JPS becomes observable as it causes a transparency window in the opaque spectral region immediately below the plasma resonance. Optical control of magnetic-flux-carrying solitons may lead to new applications in terahertz-frequency plasmonics, in information storage and transport and in the manipulation of high-Tc superconductivity.

Melting of charge stripes in vibrationally driven La(1.875)Ba(0.125)CuO4: assessing the respective roles of electronic and lattice order in frustrated superconductors.

We report femtosecond resonant soft x-ray diffraction measurements of the dynamics of the charge order and of the crystal lattice in nonsuperconducting, stripe-ordered La1.875Ba0.125CuO4. Excitation of the in-plane Cu-O stretching phonon with a midinfrared pulse has been previously shown to induce a transient superconducting state in the closely related compound La1.675Eu0.2Sr0.125CuO4. In La1.875Ba0.125CuO4, we find that the charge stripe order melts promptly on a subpicosecond time scale. Surprisingly, the low temperature tetragonal (LTT) distortion is only weakly reduced, reacting on significantly longer time scales that do not correlate with light-induced superconductivity. This experiment suggests that charge modulations alone, and not the LTT distortion, prevent superconductivity in equilibrium.

Anti-ESBL activity of silver nanoparticles biosynthesized using soil Streptomyces species.

Emergence of antibiotic resistance by bacteria has become a serious threat for public health worldwide. In this study, Streptomyces isolated from fertile soil sample was tested for biosynthesis of silver nanoparticles (AgNps) using cell-free supernatant and synthesized AgNps were screened for anti-ESBL (extended spectrum b-lactamase) activity against multi-drug resistant (MDR) ESBL-producing strain Klebsiella pneumoniae (ATCC 700603) and other medically important pathogens. Synthesis of AgNps was confirmed by change in pale yellow color to dark brown color and characteristic absorption spectra at 420 nm. The XRD spectrum displayed typical peaks of crystalline silver and EDAX analysis showed a major signal for silver. FTIR spectra revealed prominent peaks at 3,294 cm-1 (NH stretching due to amide group), 2,952 cm-1 (aldehydic C­H stretching) 1,658 cm-1 indicating the presence of carbonyl group. AgNps were spherical in shape with size ranging from 20 to 70 nm. The synthesized AgNps showed significant antimicrobial activity against standard ESBL pathogen K. pneumoniae (22 mm), 21 mm against clinical ESBL isolate E. coli and 16 mm against clinical ESBL isolates K. pneumoniae and Citrobacter species, respectively. The results of this study suggest that AgNps synthesized by Streptomyces sp. VITSJK10 can be used as a potential alternative to control MDR ESBL pathogens. The present study aimed for green synthesis of AgNps using Streptomyces species and to explore its anti-ESBL activity.

Mutations in the gene-encoding SERCA1, the fast-twitch skeletal muscle sarcoplasmic reticulum Ca2+ ATPase, are associated with Brody disease.

Brody disease is a rare inherited disorder of skeletal muscle function. Symptoms include exercise-induced impairment of skeletal muscle relaxation, stiffness and cramps. Ca2+ uptake and Ca2+ ATPase activities are reduced in the sarcoplasmic reticulum, leading to the prediction that Brody disease results from defects in the ATP2A1 gene on chromosome 16p12.1-12.2, encoding SERCA1, the fast-twitch skeletal muscle sarcoplasmic reticulum Ca2+ ATPase. A recent search, however, did not reveal any mutations in the ATP2A1 gene in three Brody patients. We have now associated Brody disease with the autosomal recessive inheritance of three ATP2A1 mutations in two families, suggesting that the disease is genetically heterogeneous. One mutation occurs at the splice donor site of intron 3, while the other two mutations lead to premature stop codons, truncating SERCA1, deleting essential functional domains and raising the intriguing question: how have these Brody patients partially compensated for the functional knockout of a gene product believed to be essential for fast-twitch skeletal muscle relaxation?

A mutation in the human ryanodine receptor gene associated with central core disease.

Central core disease (CCD) is a morphologically distinct, autosomal dominant myopathy with variable clinical features. A close association with malignant hyperthermia (MH) has been identified. Since MH and CCD genes have been linked to the skeletal muscle ryanodine receptor (RYR1) gene, cDNA sequence analysis was used to search for a causal RYR1 mutation in a CCD individual. The only amino acid substitution found was an Arg2434His mutation, resulting from the substitution of A for G7301. This mutation was linked to CCD with a lod score of 4.8 at a recombinant fraction of 0.0 in 16 informative meioses in a 130 member family, suggesting a causal relationship to CCD.

Intra-femoral tunnel graft lengths less than 20 mm do not predispose to early graft failure, inferior outcomes or poor function. A prospective clinico-radiological comparative study.

PURPOSE: Increasing demands on skills with mounting pressures from expectations from arthroscopic anterior cruciate ligament (ACL) reconstructions requires precise knowledge of technical details by surgeons. One such element is the minimum length of graft in femoral tunnel to allow for adequate tendon-to-bone healing and early return to activities and sports. This has, however, remained an unanswered question. PURPOSE: To study and compare clinico-radiological outcomes of ACL reconstructions in patients with < 20 mm of intra-femoral tunnel graft length with those measuring ≥ 20 mm. METHODS: All eligible patients undergoing arthroscopic ACL reconstruction were sequentially divided into two groups based on the intra-femoral tunnel graft lengths (A: < 20 mm, n = 27; and B: ≥ 20 mm, n = 25). Exclusions were made for those > 45 years of age, with chondral and/or multi-ligamentous injuries and with systemic pathologies. All patients were postoperatively evaluated in clinics by physical examination and functional scoring (Lysholm and modified Cincinnati scores) at 3, 6 and 12-month intervals. Graft vascularity was assessed by signal-to-noise quotient ratio (SNQR) using magnetic resonance imaging (MRI) at 3 and 12 months. RESULTS: No significant differences were noted in mean Lysholm and modified Cincinnati scores between the two groups at the end of 1 year. There were also no significant differences in graft maturation over time and SNQR at 3 and 12 months in the region of interest (ROI). CONCLUSIONS: Intra-femoral tunnel graft length of less than 20 mm does not compromise early clinical and functional outcomes of ACL reconstructions.

Evidence linking the association of periodontal viruses and pentraxins in periodontitis patients with coronary artery disease.

BACKGROUND: Although there is ample evidence in the literature supporting a significant positive association between key periodontal pathogens and established inflammatory markers of periodontitis and coronary artery disease (CAD), their exact role remain unclear. Especially, the role of viruses in the etiology and specific biomarkers have not been validated. Thus, the current study aims to evaluate the role of periodontal viruses such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus (HSV), as well as the inflammatory marker pentraxin-3 (PTX3), and to analyze their association with CAD. METHODS: The study included 240 patients divided into four groups of 60 patients each: nonperiodontitis + noncardiac (NP+NC) group, periodontitis + noncardiac patients (P+NC) group, nonperiodontitis + cardiac patients (NP+C) group, and periodontitis + cardiac (P+C) group. The cardiac surgery group (C-S) was a subgroup of NP+C and P+C. It consisted of 60 patients from the abovementioned two cardiac groups in whom coronary artery bypass graft (CABG) was indicated. Demographic variables, cardiac parameters, and periodontal parameters were recorded. The viruses (EBV, CMV, and HSV) and the inflammatory marker PTX3 were evaluated in the subgingival plaque samples of all the four groups and atheromatous plaque samples of the C-S using reverse transcriptase-polymerase chain reaction (RT-PCR) and quantitative polymerase chain reaction (qPCR), respectively, and were compared between the groups. The results were obtained and statistically analyzed. RESULTS: The demographic variables did not differ significantly between the groups, except for age. Systolic blood pressure, diastolic blood pressure, low-density lipoprotein, and random blood sugar were significantly higher in NP+C and P+C, whereas high-density lipoprotein was significantly lower (p ≤ 0.05) in the same. Plaque index (PI), probing pocket depth (PPD), and clinical attachment level (CAL) were significantly higher (p ≤ 0.05) in P+NC and P+C. PTX were significantly elevated in P+C among the four groups. On evaluating the subgingival plaque samples, EBV and CMV were significantly higher in the two periodontitis groups P+NC and P+C (p = 0.000). HSV was significantly higher in the two cardiac groups (NP+C and P+C) (p ≤ 0.05). Cardiac EBV and CMV were significantly elevated in the P+C group with a p value of 0.004 and 0.033, respectively. Cardiac HSV was found in the NP+C group with statistical insignificance (p = 0.410) between the groups. On correlation, oral PTX were significantly associated with bleeding index (BI), PPD, and CAL (p = 0.000). Similarly, cardiac PTX showed significant association with PI, BI, PPD, and CAL (p = 0.000). Oral and cardiac PTX also showed significant correlation with each other. Multiple logistic regression analysis revealed a significant association between CAL and oral EBV (p ≤ 0.05). Similarly, cardiac EBV showed a significant association with CAL and oral EBV (p ≤ 0.05). Multiple logistic regression analysis also revealed that both cardiac and oral PTX showed a significant association only with oral EBV, CMV, and HSV. CONCLUSION: The results of the current study suggest that the clinical severity of periodontitis (CAL), etiology of periodontitis (EBV and CMV), and inflammatory marker of periodontitis (PTX3) were found to be significantly elevated in CAD. These findings suggests that periodontal diseases may be a risk factor that could influence the progression of CAD.

Association of pentraxin in periodontitis patients with coronary artery disease.

Objectives: Pentraxin 3 (PTX3) is a biomarker, associated with the pathogenesis of Periodontitis and coronary artery disease (CAD) individually, but their role in patients with both diseases remains unclear. The current study aims to evaluate the association of PTX in patients with concomitant periodontitis and CAD. Materials and Methods: In a case-control study, 240 participants were selected and divided into four groups. Nonperiodontitis + noncardiac = 60 patients, periodontitis + noncardiac (P + NC) = 60 patients, nonperiodontitis + cardiac (NP + C) = 60 patients, periodontitis + cardiac (P + C) = 60 patients. Demographic variables, cardiac and periodontal parameters were recorded. PTX was evaluated in the subgingival plaque and atheromatous plaque samples using real-time quantitative polymerase chain reaction and compared between the groups. The results were statistically analyzed. Results: Among the demographic variables, age showed a significant difference between the groups. Systolic and diastolic blood pressure, low-density lipoprotein, and random blood sugar were significantly higher in NP + C and P + C groups (P ≤ 0.05). The plaque index, probing pocket depth, and clinical attachment loss were significantly higher in P + NC and P + C groups (P ≤ 0.05). PTX was significantly elevated in P + C group (P = 0.000). Pearson's correlation revealed a significant correlation between the periodontal parameters and PTX in both the cardiac and oral samples. Conclusion: PTX3 levels were elevated in CAD patients with periodontitis suggesting the influence of periodontal inflammation in the progression of CAD. PTX3 may serve as a diagnostic and prognostic tool for both periodontitis and CAD. This study could provide an understanding and awareness about the potential role of PTX3 in both periodontitis and CAD.

Insights of Extracellular Vesicles of Mesenchymal Stem Cells: a Prospective Cell-Free Regenerative Medicine for Neurodegenerative Disorders.

Mesenchymal stem cells (MSCs) are multipotent, adult stem cells which are found in numerous tissues like the umbilical cord, Wharton's jelly, bone marrow, and adipose tissue. They possess the capacity of self-renewal by dividing and differentiating into various cellular lineages. Their characteristic therapeutic potential exploited so far has made them a desirable candidate in regenerative medicine. Neurodegenerative diseases (NDs) like Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and ischemic stroke have been treated with MSCs and MSC-derived products. Over the past few decades, we have witnessed significant contributions in discovering the etiology of various NDs and their possible therapeutic solutions. One of the MSC-based therapeutics is extracellular vesicles (EVs), which contain multiple biologically active molecules like nucleic acids and proteins. The contents of EVs are ferried between cells for intercellular communication which then leads to regulation of the homeostasis of recipient cells. EVs serve as a considerable means of cell-free therapies like for tissue repair or regeneration as EVs can maintain therapeutically effective cargo of parent cells and are free of various ethical issues in cell-based therapies. Due to paucity of standard protocols in extraction procedures of EVs and their pharmacological properties and mechanisms, the development of new EV dependent therapies is challenging. With this review, an attempt has been made to annotate these mechanisms, which can help advance the novel therapeutic approaches towards the treat and define a more narrowed down approach for each ND to devise effective MSC-based therapies to cure and avert these diseases.

Photoinduced melting of antiferromagnetic order in La(0.5)Sr(1.5)MnO4 measured using ultrafast resonant soft x-ray diffraction.

We used ultrafast resonant soft x-ray diffraction to probe the picosecond dynamics of spin and orbital order in La(0.5)Sr(1.5)MnO(4) after photoexcitation with a femtosecond pulse of 1.5 eV radiation. Complete melting of antiferromagnetic spin order is evidenced by the disappearance of a (1/4,1/4,1/2) diffraction peak. On the other hand, the (1/4,1/4,0) diffraction peak, reflecting orbital order, is only partially reduced. We interpret the results as evidence of destabilization in the short-range exchange pattern with no significant relaxation of the long-range Jahn-Teller distortions. Cluster calculations are used to analyze different possible magnetically ordered states in the long-lived metastable phase. Nonthermal coupling between light and magnetism emerges as a primary aspect of photoinduced phase transitions in manganites.

Atrial fibrillation: epidemiology, prognosis and therapy.

Atrial fibrillation is the most common cardiac tachyarrhythmia encountered in clinical practice affecting 1% of the population. It is characterized by uncoordinated atrial activation that can lead to embolic complications and reduction in cardiac output resulting in significant morbidity, mortality and a reduction in quality of life. The three major goals in the management of atrial fibrillation are rate control, prevention of thromboembolism and correction of rhythm disturbance. This article will review up-to-date thinking about strategies for achieving each of these fundamental goals of AF care, with an emphasis on new drugs such as dabigatran and dronedarone and emerging non-pharmacologic therapies such as catheter ablation and left atrial appendage exclusion. After many years with relatively few new treatments, the past few years have seen a number of exciting developments which will hopefully improve clinician's ability to improve the outcomes of patients with this chronic and troublesome condition.

Caspase cascade regulated mitochondria mediated apoptosis in monocrotophos exposed PC12 cells.

Monocrotophos (MCP) is a commonly used organophosphorus (OP) pesticide. We studied apoptotic changes in PC12 cells exposed to MCP. A significant induction in reactive oxygen species (ROS), lipid peroxide (LPO), and the ratio of glutathione disulfide (GSSG)/reduced glutathione (GSH) was observed in cells exposed to selected doses of MCP. Following the exposure of PC12 cells to MCP, the levels of protein and mRNA expressions of Caspase-3, Caspase-9, Bax, p53, P(21), Puma, and cytochrome-c were significantly upregulated, whereas the levels of Bcl(2), Bcl(w), and Mcl1 were downregulated. TUNEL assay, DNA laddering, and micronuclei induction show that long-term exposure of PC12 cells to MCP at higher concentration (10(-5) M) decreases the number of apoptotic events due to an increase in the number of necrotic cells. MCP-induced translocation of Bax and cytochrome-c proteins between the cytoplasm and mitochondria confirmed the role of p53 and Puma in mitochondrial membrane permeability. Mitochondria mediated apoptosis induction was confirmed by the increased activity of caspase cascade. We believe that this is the first report showing MCP-induced apoptosis in PC12 cells, which is mitochondria mediated and regulated through the caspase cascade. Our data demonstrates that MCP induced the apoptotic cell death in neuronal cells and identifies the possible cellular and molecular mechanisms of organophosphate pesticide-induced apoptosis in neuronal cells.

Association of dopamine DA-D2 receptor in rotenone-induced cytotoxicity in PC12 cells.

The investigations were aimed to study the possible association of dopamine DA-D(2) receptor in rotenone-induced cytotoxicity in PC12 cells, one among the most studied cell line in neurotoxicity studies. PC12 cells were subjected to receive an exposure of rotenone (10(-6) to 10(-4) M) for 24 and 48 hours. Cytotoxicity studies were carried out using standard end points including, (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT), lactate dehydrogenase (LDH) release and neutral red uptake (NRU). Cells were found to be vulnerable to rotenone in dose-dependent manner. In general, 10(-4) and 10(-5) M concentrations were found to be cytotoxic, whereas 10(-6) M and lower concentrations used have shown nonsignificant effect on cell viability. Further, studies were extended to study the rotenone-induced alterations in cellular glutathione (GSH) level and dopamine DA-D(2) receptor expression. Significant (p < 0.001) chronological depletion in GSH levels were recorded following rotenone exposure. Expression of dopamine DA-D(2) receptor was also found to be effected significantly (p < 0.001) at 24 hours of rotenone exposure (10(-4) and 10(-5)). However, no further depletion in the expression of dopamine DA-D(2) receptor could be recorded with extended exposure period, that is, 48 hours. Rotenone at 10(-6) M and lower concentrations was found to be ineffective in PC12 cells. Data suggest the vulnerability of PC12 cells against experimental exposure of rotenone, which possibly routed through dopamine DA-D(2) receptor and oxidative stress machinery.

Association of severity of COPD with IgE and interleukin-1 beta.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a pulmonary inflammatory disease characterised by airflow limitation. The role of various inflammatory mediators such as interleukin-1beta (IL-beta) and Immunoglobulin E (IgE) have been implicated in COPD. In present study we aimed to establish if there is an association between the serum levels of IL-1beta and IgE and the severity of airway obstruction. MATERIALS AND METHODS: The study group comprised of 30 non atopic smokers, suffering from COPD and 30 non smoker, healthy controls. Serum levels of IgE and IL-1beta were assayed by ELISA in all subjects along with their pulmonary function tests. RESULTS: Serum IgE and IL-1beta levels were significantly raised in COPD patients as compared to healthy controls. IL-1beta was negatively correlated with FEV1 (r = -0.624, p = 0.003) and IgE showed a negative correlation with FVC (r = -0.477, p = 0.034). CONCLUSION: Our study suggests that in COPD IL-1beta and IgE serum levels correlate with clinical aspects of disease severity. We suggest that the production of IgE and IL-1beta in the airways of patients with COPD may be related to smoking which affects airway obstruction.

PRP versus steroids in a deadlock for efficacy: long-term stability versus short-term intensity-results from a randomised trial.

PURPOSE: A popular choice for lateral epicondylitis (LE), corticosteroid injections have been associated with prominent side effects, which has led to the conception of modalities like platelet-rich plasma (PRP). This randomised trial aimed to evaluate and compare the 6-week, 3-month and 1-year outcomes with PRP and corticosteroid injections in LE. We hypothesised that PRP would prove more effective in relieving pain and improving function. METHODS: At the sports medicine unit of our tertiary care teaching centre, 80 patients with LE were randomised into either receiving PRP (group A) or corticosteroids (group B) injections. Pre-injection visual analogue scale (VAS), disabilities of the arm, shoulder and hand (DASH) score, Mayo elbow performance score (MEPS) and grip strength score (GSS) were recorded. Common extensor origins were identified and infiltrated with 3 ml of either PRP or corticosteroid (triamcinolone in 2% xylocaine) using a peppering technique. Follow-up scores and extent of pain relief were recorded and compared. RESULTS: At 6 weeks, there were greater improvements in group B versus A in mean VAS (13.8 vs. 44.5; p < 0.001), DASH (64.2 vs. 53.3; p < 0.001), MEPS (88.0 vs. 74.5; p = 0.004) and GSS (89.3 vs. 73.4; p = 0.039). These scores showed a reversed pattern at 3 months when group A outcomes superseded group B (VAS p = 0.002; DASH p < 0.001; MEPS p = 0.002; GSS p = 0.045). At 1-year follow-up, group A continued to enjoy better pain relief and function (VAS p = 0.024; DASH p < 0.001; MEPS p = 0.009; GSS p = 0.028). CONCLUSIONS: Albeit corticosteroid injections show good short-term results at 6 weeks, patients receiving PRP injections fare better at 3 and 12 months.