Unveiling the Biocontrol Potential of Rhizoplane Bacillus Species against Sugarcane Fusarium Wilt through Biochemical and Molecular Analysis.

BACKGROUND: Biocontrol is regarded as a viable alternate technique for managing sugarcane wilt disease caused by Fusarium sacchari. Many fungal antagonists against F. sacchari, have been reported, but the potential of bacterial antagonists was explored to a limited extent, so the present study evaluated the antagonistic potential of rhizoplane Bacillus species and their mode of action. RESULTS: A total of twenty Bacillus isolates from the rhizoplane of commercially grown sugarcane varieties were isolated. The potential isolate SRB2 had shown inhibition of 52.30, 33.33, & 44.44% and SRB20 of 35.00, 33.15, & 36.85% in direct, indirect, and remote confrontation respectively against F. sacchari. The effective strains were identified as Bacillus inaquosorum strain SRB2 and B. vallismortis strain SRB20, by PCR amplification of 16S-23S intergenic region. The biochemical studies on various direct and indirect biocontrol mechanisms revealed the production of IAA, Protease, Cellulase, Siderophores, and P solubilization. The molecular analysis revealed the presence of antimicrobial peptides biosynthetic genes like fenD (Fengycin), bmyB (Bacyllomicin) ituC (Iturin) and spaS (Subtilin) which provided a competitive edge to these isolates compared to other Bacillus strains. Under greenhouse experiments, the sett bacterization with SRB2, significantly (P < 0.001) reduced the seedling mortality by > 70% followed by SRB20 in F. sacchari inoculated pots. CONCLUSION: The study revealed that the isolates B. inaquosorum SRB2 and B. vallismortis SRB20 can be used as potential bioagents against sugarcane Fusarium wilt.

Out-of-Hospital Cardiac Arrest during the COVID-19 Pandemic: A Systematic Review.

Objective: Out-of-hospital cardiac arrest (OHCA) is a prominent cause of death worldwide. As indicated by the high proportion of COVID-19 suspicion or diagnosis among patients who had OHCA, this issue could have resulted in multiple fatalities from coronavirus disease 2019 (COVID-19) occurring at home and being counted as OHCA. Methods: We used the MeSH term "heart arrest" as well as non-MeSH terms "out-of-hospital cardiac arrest, sudden cardiac death, OHCA, cardiac arrest, coronavirus pandemic, COVID-19, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)." We conducted a literature search using these search keywords in the Science Direct and PubMed databases and Google Scholar until 25 April 2022. Results: A systematic review of observational studies revealed OHCA and mortality rates increased considerably during the COVID-19 pandemic compared to the same period of the previous year. A temporary two-fold rise in OHCA incidence was detected along with a drop in survival. During the pandemic, the community's response to OHCA changed, with fewer bystander cardiopulmonary resuscitations (CPRs), longer emergency medical service (EMS) response times, and worse OHCA survival rates. Conclusions: This study's limitations include a lack of a centralised data-gathering method and OHCA registry system. If the chain of survival is maintained and effective emergency ambulance services with a qualified emergency medical team are given, the outcome for OHCA survivors can be improved even more.

Observation of Zero-Field Transverse Resistance in AlO_{x}/SrTiO_{3} Interface Devices.

Domain walls in AlO_{x}/SrTiO_{3} (AlO_{x}/STO) interface devices at low temperatures give a rise to a new signature in the electrical transport of two-dimensional carrier gases formed at the surfaces or interfaces of STO-based heterostructures: a finite transverse resistance observed in Hall bars in zero external magnetic field. This transverse resistance depends on the local domain wall configuration and hence changes with temperature, gate voltage, thermal cycling, and position along the sample and can even change sign as a function of these parameters. The transverse resistance is observed below ≃70 K but grows and changes significantly below ≃40 K, the temperature at which the domain walls become increasingly polar. Surprisingly, the transverse resistance is much larger in (111) oriented heterostructures in comparison to (001) oriented heterostructures. Measurements of the capacitance between the conducting interface and an electrode applied to the substrate, which reflect the dielectric constant of the STO, indicate that this difference may be related to the greater variation of the temperature-dependent dielectric constant with electric field when the electric field is applied in the [111] direction. The finite transverse resistance can be explained inhomogeneous current flow due to the preferential transport of current along domain walls that are askew to the nominal direction of the injected current.

Prevalence of Stroke Cases in Warangal, Telangana Region, India: A Hospital-Based Case Study.

Stroke is becoming a main cause of early death and disability in developing countries like India, and it is mostly enhanced by increased predominance of major risk factors. A detailed knowledge about the nature and magnitude of the stroke cases in this particular area is not only important for acute treatment but also it helps to prevent hospital admissions due to reoccurring stroke. The present study was conducted in the Department of Stroke at MGM Hospital, Warangal, India, to study the patterns of stroke admissions. All the collected data were compiled and analyzed using appropriate statistical tools. The mean age of study population was found to be 58.9 ± 18. Only 2.7% of stroke incidents occurred in people aged ≤40 years old, 4.9% of cases concerned people between 41 and 50 years old, 18.2% of the incidents happened when the subjects were between 51 and 60 years old, and in 74.2% of the cases, the individuals were ≥60 years old. The frequencies of ischemic (IS), subarachnoid hemorrhage (SAH), and intracerebral hemorrhage (ICH) in Warangal region were 57.9%, 7.3%, and 29.2%, respectively. A statistically significant association was found for both smoking (χ2 = 419.1 and p < 0.001) and alcohol (χ2 = 68.7 and p < 0.001) as risk factors in stroke. From this study, it was apparent that in Telangana region, there is a need to provide structured clinical management in treating emergency stroke cases and implement stroke care services with organized multidisciplinary teams.

Discovery and Structure-Activity Relationship Study of (Z)-5-Methylenethiazolidin-4-one Derivatives as Potent and Selective Pan-phosphatidylinositol 5-Phosphate 4-Kinase Inhibitors.

Due to their role in many important signaling pathways, phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are attractive targets for the development of experimental therapeutics for cancer, metabolic, and immunological disorders. Recent efforts to develop small molecule inhibitors for these lipid kinases resulted in compounds with low- to sub-micromolar potencies. Here, we report the identification of CVM-05-002 using a high-throughput screen of PI5P4Kα against our in-house kinase inhibitor library. CVM-05-002 is a potent and selective inhibitor of PI5P4Ks, and a 1.7 Å X-ray structure reveals its binding interactions in the ATP-binding pocket. Further investigation of the structure-activity relationship led to the development of compound 13, replacing the rhodanine-like moiety present in CVM-05-002 with an indole, a potent pan-PI5P4K inhibitor with excellent kinome-wide selectivity. Finally, we employed isothermal cellular thermal shift assays (CETSAs) to demonstrate the effective cellular target engagement of PI5P4Kα and -ß by the inhibitors in HEK 293T cells.

Structural Tuning of Anion-Templated Motifs with External Stimuli through Crystal-to-Crystal Transformation.

Protonation of trans-1,2-bis(4-pyridyl)ethylene (4,4'-bpe) with dilute sulfuric acid (33 %) afforded a protonated adduct [{4,4'-bpe⋅2 H+ }2 {HSO4 }-2 {SO4 }-2 {H2 O}2 ] (1). The neighboring olefinic bond in 1 is in a suitable range (3.931-4.064 Å) to undergo a photochemical [2+2] cycloaddition reaction. Upon irradiation with UV light (365 nm), 1 undergoes a molecular sliding involving the 4,4'-bpe⋅2 H+ units, affording 2, stabilized through OSO4 ⋅⋅⋅π interactions. Heating 1 to 50° C leads to a 3D hydrogen-bonded organic framework (HOF) (3). This process occurs through thermal dissociation of the bisulfate anion. Diffusion of iodine through the crystal lattice of 1 and 3 enables the reduction of sulfate to bisulfate, affording a 1D hydrogen-bonded chain (4). Solid-state 13 C CPMAS NMR, IR, DSC, and powder XRD studies further support stimuli-responsive structural tuning through crystal-to-crystal transformation. All these conversions occur with significant translational and rotational movements along with a series of bond-breaking and bond-forming processes.

A rare cause of recalcitrant coccydynia: benign dermoid cyst masquerading as coccygeal pain.

PURPOSE: Coccydynia is a common entity in orthopedic practice, and various etiologies have been described for it. However, benign dermoid cyst causing coccydynia has not yet been reported. METHODS: A 20-year-old male presented with typical symptoms of coccydynia recalcitrant to conservative treatment for 2 years. Since pain interfered with his daily activities, magnetic resonance imaging was performed which showed a circumscribed precoccygeal cystic lesion. RESULTS: The patient underwent coccygectomy along with cyst excision. Histological examination revealed features of benign dermoid cyst. After surgery, the patient had excellent relief of his symptoms. CONCLUSION: The case report identifies that the treating surgeon should be aware of benign dermoid cyst as one of the treatable but rare causes of intractable coccydynia, and MRI should be performed in patients with persistent coccygeal pain.

Effect of three different remineralizing agents on enamel caries formation--an in vitro study.

BACKGROUND: Caries process is not a static one, but is dynamic with interspersed periods of demineralization and remineralization of enamel, intimately related and occurs episodically based upon the presence of cariogenic bacteria in dental plaque and the availability of refined carbohydrates for fermentation to organic acids. OBJECTIVES: Early enamel caries could be reversed with avoidance of frank cavitation. The main objective of this study is to check wether enamel demineralization can be prevented by using the remineralizing agents. METHOD: Forty freshly extracted human central incisors were selected and stored in saline at normal temperature. A window of 3 X 3mm enamel was created and all the specimens were then randomly divided into 4 groups of 10 each. Group I--teeth received no treatment, Group II--teeth treated with Acidulated Phosphate Flouride gel, Group III--teeth treated with Tooth Mousse Plus, Group IV--teeth treated with Remin+. Samples in all the groups were kept in artificial saliva for 24 hours and subjected to modified Ten Cate's solution at an acidic pH of 3.5 for 10 days. The samples were sectioned and subjected to SEM evaluation. RESULT: Scanning Electron Microscope(SEM) images showed decrease in pore volume of the enamel in all the treatment groups compared to the control group indicating increase in resistance to demineralization in acidic pH. CONCLUSION: The three groups of remineralizing agents, Acidulated Phosphate Fluoride gel, Tooth Mousse Plus and Remin + showed significant increase in fluoride content and negligible increase in calcium content indicating there is remineraliztion.

Chemical interrogation of the malaria kinome.

Malaria, an infectious disease caused by eukaryotic parasites of the genus Plasmodium, afflicts hundreds of millions of people every year. Both the parasite and its host utilize protein kinases to regulate essential cellular processes. Bioinformatic analyses of parasite genomes predict at least 65 protein kinases, but their biological functions and therapeutic potential are largely unknown. We profiled 1358 small-molecule kinase inhibitors to evaluate the role of both the human and the malaria kinomes in Plasmodium infection of liver cells, the parasites' obligatory but transient developmental stage that precedes the symptomatic blood stage. The screen identified several small molecules that inhibit parasite load in liver cells, some with nanomolar efficacy, and each compound was subsequently assessed for activity against blood-stage malaria. Most of the screening hits inhibited both liver- and blood-stage malaria parasites, which have dissimilar gene expression profiles and infect different host cells. Evaluation of existing kinase activity profiling data for the library members suggests that several kinases are essential to malaria parasites, including cyclin-dependent kinases (CDKs), glycogen synthase kinases, and phosphoinositide-3-kinases. CDK inhibitors were found to bind to Plasmodium protein kinase 5, but it is likely that these compounds target multiple parasite kinases. The dual-stage inhibition of the identified kinase inhibitors makes them useful chemical probes and promising starting points for antimalarial development.

PIM kinases are essential for chronic lymphocytic leukemia cell survival (PIM2/3) and CXCR4-mediated microenvironmental interactions (PIM1).

Overexpression of the CXCR4 receptor is a hallmark of chronic lymphocytic leukemia (CLL) and is important for CLL cell survival, migration, and interaction with their protective microenvironment. In acute myelogenous leukemia (AML), PIM1 was shown to regulate the surface expression of the CXCR4 receptor. Here, we show that PIM (proviral integration site for Moloney murine leukemia virus) kinases 1-3 are overexpressed and that the CXCR4 receptor is hyperphosphorylated on Ser339 in CLL compared with normal lymphocytes. Furthermore, CXCR4 phosphorylation correlates with PIM1 protein expression and PIM1 transcript levels in CLL. PIM kinase inhibition with three different PIM kinase inhibitors induced apoptosis in CLL cells independent of the presence of protective stromal cells. In addition, PIM inhibition caused dephosphorylation of the CXCR4 receptor on Ser339, resulting in enhanced ligand-dependent CXCR4 internalization and reduced re-externalization after withdrawal of CXCL12. Furthermore, PIM inhibition in CLL cells blocked CXCR4 functions, such as migration toward CXCL12- or CXCL12-induced extracellular signal-regulated kinase (ERK) phosphorylation. In concordance, pretreatment of CLL cells with PIM kinase inhibitors strongly reduced homing of CLL cells toward the bone marrow and the spleen of Rag2(-/-)γc(-/-) mice in vivo. Interestingly, the knockdown of PIM kinases in CLL cells demonstrated diverging functions, with PIM1 regulating CXCR4 surface expression and PIM2 and PIM3 as important for the survival of CLL cells. Our results show that PIM kinase inhibitors are an effective therapeutic option for CLL, not only by impairing PIM2/3-mediated CLL cell survival, but also by blocking the PIM1/CXCR4-mediated interaction of CLL cells with their protective microenvironment.

A hybrid analog-digital phase-locked loop for frequency mode non-contact scanning probe microscopy.

Non-contact scanning probe microscopy (SPM) has developed into a powerful technique to image many different properties of samples. The conventional method involves monitoring the amplitude, phase, or frequency of a cantilever oscillating at or near its resonant frequency as it is scanned across the surface of a sample. For high Q factor cantilevers, monitoring the resonant frequency is the preferred method in order to obtain reasonable scan times. This can be done by using a phase-locked-loop (PLL). PLLs can be obtained as commercial integrated circuits, but these do not have the frequency resolution required for SPM. To increase the resolution, all-digital PLLs requiring sophisticated digital signal processors or field programmable gate arrays have also been implemented. We describe here a hybrid analog/digital PLL where most of the components are implemented using discrete analog integrated circuits, but the frequency resolution is provided by a direct digital synthesis chip controlled by a simple peripheral interface controller (PIC) microcontroller. The PLL has excellent frequency resolution and noise, and can be controlled and read by a computer via a universal serial bus connection.

RTSPM: real-time Linux control software for scanning probe microscopy.

Real time computer control is an essential feature of scanning probe microscopes, which have become important tools for the characterization and investigation of nanometer scale samples. Most commercial (and some open-source) scanning probe data acquisition software uses digital signal processors to handle the real time data processing and control, which adds to the expense and complexity of the control software. We describe here scan control software that uses a single computer and a data acquisition card to acquire scan data. The computer runs an open-source real time Linux kernel, which permits fast acquisition and control while maintaining a responsive graphical user interface. Images from a simulated tuning-fork based microscope as well as a standard topographical sample are also presented, showing some of the capabilities of the software.

Use of warfarin therapy among residents who developed venous thromboembolism in the nursing home.

BACKGROUND: Treatment of venous thromboembolism (VTE) in long-term care (LTC) settings has received little empirical study. OBJECTIVE: Among residents with VTE in nursing homes, this analysis evaluated frequency of anticoagulant use, the proportion of residents newly started on warfarin who persisted on therapy (≥3 months), and the association of key resident characteristics, including bleeding risk, with warfarin use and persistence. METHODS: Using the AnalytiCare LTC database (US), eligible residents had deep vein thrombosis or pulmonary embolism coded in the Minimum Data Set (MDS) 2.0 during the uptake period April 1, 2007 through December 31, 2008 (earliest VTE was index date) and had 1 or more MDS assessment(s) over the 90-day preindex period, each negative for VTE. Logistic regression evaluated the association of resident characteristics with warfarin use. Cox regression evaluated persistence with warfarin therapy. RESULTS: The median age of residents with VTE included in the analysis (N = 489) was 80 years; 73% received anticoagulant therapy and 66% were prescribed warfarin ±45 days of the index date. Multivariate logistic regression identified several factors significantly associated with warfarin use: location in South Central region (odds ratio [OR] = 1.94, P = 0.019) and the Western region (OR = 2.53, P = 0.005) [both vs reference South Atlantic]; body mass index categories normal (OR = 2.73, P = 0.045), overweight (OR = 4.21, P = 0.005), and obese (OR = 3.82, P = 0.010) (both vs reference underweight); Alzheimer's/dementia (OR = 0.52, P = 0.024); cancer (OR = 0.39, P = 0.008); and moderate-dependent versus independent physical functioning (OR = 2.59, P = 0.003). Of residents newly started on warfarin therapy with no history of cancer (n = 149), 28% discontinued warfarin within 90 days of initiation. Peripheral vascular disease (PVD) (OR = 4.07, P < 0.001), Alzheimer's disease/dementia (OR = 2.55, P = 0.046), and antipsychotic use (OR = 4.60, P < 0.001) were all significantly associated with discontinuation. CONCLUSIONS: Patients in specific geographic regions who were underweight, had Alzheimer's disease/dementia or cancer, or had independent physical functioning were less likely to receive warfarin. Nonpersistence of warfarin therapy was strongly related to antipsychotic use, presence of dementia, or PVD.

Evidence for charge-vortex duality at the LaAlO3/SrTiO3 interface.

The concept of duality has proved extremely powerful in extending our understanding in many areas of physics. Charge-vortex duality has been proposed as a model to understand the superconductor to insulator transition in disordered thin films and Josephson junction arrays. In this model, on the superconducting side, one has delocalized Cooper pairs but localized vortices; while on the insulating side, one has localized Cooper pairs but mobile vortices. Here we show a new experimental manifestation of this duality in the electron gas that forms at the interface between LaAlO(3) and SrTiO(3). The effect is due to the motion of vortices generated by the magnetization dynamics of the ferromagnet that also forms at the same interface, which results in an increase in resistance on the superconducting side of the transition, but an increase in conductance on the insulating side.

High-throughput kinase profiling: a more efficient approach toward the discovery of new kinase inhibitors.

Selective protein kinase inhibitors have only been developed against a small number of kinase targets. Here we demonstrate that "high-throughput kinase profiling" is an efficient method for the discovery of lead compounds for established as well as unexplored kinase targets. We screened a library of 118 compounds constituting two distinct scaffolds (furan-thiazolidinediones and pyrimido-diazepines) against a panel of 353 kinases. A distinct kinase selectivity profile was observed for each scaffold. Selective inhibitors were identified with submicromolar cellular activity against PIM1, ERK5, ACK1, MPS1, PLK1-3, and Aurora A,B kinases. In addition, we identified potent inhibitors for so far unexplored kinases such as DRAK1, HIPK2, and DCAMKL1 that await further evaluation. This inhibitor-centric approach permits comprehensive assessment of a scaffold of interest and represents an efficient and general strategy for identifying new selective kinase inhibitors.

Coexistence of superconductivity and ferromagnetism in two dimensions.

Ferromagnetism is usually considered to be incompatible with conventional superconductivity, as it destroys the singlet correlations responsible for the pairing interaction. Superconductivity and ferromagnetism are known to coexist in only a few bulk rare-earth materials. Here we report evidence for their coexistence in a two-dimensional system: the interface between two bulk insulators, LaAlO(3) (LAO) and SrTiO(3) (STO), a system that has been studied intensively recently. Magnetoresistance, Hall, and electric-field dependence measurements suggest that there are two distinct bands of charge carriers that contribute to the interface conductivity. The sensitivity of properties of the interface to an electric field makes this a fascinating system for the study of the interplay between superconductivity and magnetism.

Microenvironmental influence on pre-clinical activity of polo-like kinase inhibition in multiple myeloma: implications for clinical translation.

Polo-like kinases (PLKs) play an important role in cell cycle progression, checkpoint control and mitosis. The high mitotic index and chromosomal instability of advanced cancers suggest that PLK inhibitors may be an attractive therapeutic option for presently incurable advanced neoplasias with systemic involvement, such as multiple myeloma (MM). We studied the PLK 1, 2, 3 inhibitor BI 2536 and observed potent (IC50<40 nM) and rapid (commitment to cell death <24 hrs) in vitro activity against MM cells in isolation, as well as in vivo activity against a traditional subcutaneous xenograft mouse model. Tumor cells in MM patients, however, don't exist in isolation, but reside in and interact with the bone microenvironment. Therefore conventional in vitro and in vivo preclinical assays don't take into account how interactions between MM cells and the bone microenvironment can potentially confer drug resistance. To probe this question, we performed tumor cell compartment-specific bioluminescence imaging assays to compare the preclinical anti-MM activity of BI 2536 in vitro in the presence vs. absence of stromal cells or osteoclasts. We observed that the presence of these bone marrow non-malignant cells led to decreased anti-MM activity of BI 2536. We further validated these results in an orthotopic in vivo mouse model of diffuse MM bone lesions where tumor cells interact with non-malignant cells of the bone microenvironment. We again observed that BI 2536 had decreased activity in this in vivo model of tumor-bone microenvironment interactions highlighting that, despite BI 2536's promising activity in conventional assays, its lack of activity in microenvironmental models raises concerns for its clinical development for MM. More broadly, preclinical drug testing in the absence of relevant tumor microenvironment interactions may overestimate potential clinical activity, thus explaining at least in part the gap between preclinical vs. clinical efficacy in MM and other cancers.

Post cementation sensitivity evaluation of glass Ionomer, zinc phosphate and resin modified glass Ionomer luting cements under class II inlays: An in vivo comparative study.

OBJECTIVE: This study aims to compare the patient-perceived post-cementation sensitivity of class II metal restorations preoperatively, immediately after cementation, one week after cementation and one month after cementation with (1) Glass Ionomer luting cement (2) Zinc Phosphate cement and (3) Resin-modified Glass Ionomer luting cement. MATERIALS AND METHODS: A total of 60 patients, irrespective of sex, in the age group of 15-50 years were selected and the teeth were randomly divided into three groups of 20 each. Twenty inlay cast restorations were cemented with three different luting cements. The criteria adapted to measure tooth sensitivity in the present study were objective examination for sensitivity. (1) Cold water test (2) Compressed air test and (3) Biting pressure test. RESULTS: The patients with restorations cemented with Resin-modified Glass ionomer demonstrated the least postoperative sensitivity when compared with Glass Ionomer and zinc phosphate cement at all different intervals of time evaluated by different tests. CONCLUSION: The patients with restorations cemented with resin-modified Glass ionomer demonstrated the least postoperative sensitivity.

Maxillary molar with two palatal roots: Two case reports.

An awareness and understanding of the presence of an additional root and unusual root canal morphology is essential as it determines the successful outcome of endodontic treatment. Aberrations in root canal anatomy are commonly occurring phenomena. A thorough knowledge of basic root canal anatomy and its variation is necessary for successful completion of endodontic treatment. This report points to the importance of looking for additional roots and canals because knowledge of their existence would enable clinician to treat a case successfully that otherwise might end in failure.

Phase-incoherent superconducting pairs in the normal state of Ba(Fe(1-x)Co(x))2As2.

The normal state properties of the recently discovered ferropnictide superconductors might hold the key to understanding their exotic superconductivity. Using point-contact spectroscopy we show that Andreev reflection between an epitaxial thin film of Ba(Fe(0.92)Co(0.08))2As2 and a silver tip can be seen in the normal state of the film up to temperature T∼1.3T(c), where T(c) is the critical temperature of the superconductor. Andreev reflection far above T(c) can be understood only when superconducting pairs arising from strong fluctuation of the phase of the complex superconducting order parameter exist in the normal state. Our results provide spectroscopic evidence of phase-incoherent superconducting pairs in the normal state of the ferropnictide superconductors.