Microbial-based therapy of cancer: a new twist to age old practice

The use of bacteria in the regression of tumors has long been known. Various approaches for using bacteria in cancer therapy include the use of bacteria as sensitizing agents for chemotherapy, as delivery agents for cancer drugs and as agents for gene therapy. The tumor regression stimulated by infecting microorganisms has been attributed to activation of the immune system of the host. However, recent studies indicate that when tumor-harboring mice with defective immune systems are infected with certain microorganisms, the regression of the tumor is still observed, suggesting that there are other host factors contributing to the microbial associated regression of tumors. Since the use of live or attenuated bacteria for tumor regression has associated toxic effects, studies are in progress to identify a pure microbial metabolite or any component of the microbial cell that might have anti-cancer activity. It has now been demonstrated that a redox protein from Pseudomonas aeruginosa, a cupredoxin, can enter into human cancer cells and trigger the apoptotic cell death. In vivo, this cupredoxin can lead to the regression of tumor growth in immunodeficient mice harboring xenografted melanomas and breast cancer tumors without inducing significant toxic effects, suggesting that it has potential anti-cancer activity. This bacterial protein interacts with p53 and modulates mammalian cellular activity. Hence, it could potentially be used as an anti-cancer agent for solid tumors and has translational value in tumor-targeted or in combinational-biochemotherapy strategies for cancer treatments. Here, we focus on diverse approaches to cancer biotherapy, including bacteriolytic and bacterially-derived anti-cancer agents with an emphasis on their mechanism of action and therapeutic potential

Pattern and trends of respiratory diseases in an outpatient setting: a five-year review in a tertiary hospital in South-South, Nigeria

Background: Limited information exists on the epidemiology of respiratory diseases in South-South Nigeria, especially regarding changing risk factors. This study aimed to assess the frequency and pattern of respiratory diseases in an adult outpatient clinic in a teaching hospital in South-South Nigeria. Methods: Medical records of newly referred patients with respiratory diseases who received care at the chest clinic of Irrua Specialist Teaching Hospital from January 2018 to December 2022 were retrospectively reviewed. Results: The study included 655 patients (mean age: 54.7±18.7 years). The majority of cases occurred in the 41-60 age group, and 55.4% were female. Non-communicable respiratory diseases accounted for 60.9% of cases, while communicable respiratory diseases accounted for 39.1%. The most common respiratory diseases observed were bronchial asthma (22.6%), tuberculosis (21.1%), chronic obstructive pulmonary disease (19.2%), pneumonia (11.1%), interstitial lung diseases (6.7%), and lung cancer (4.1%). Less common respiratory diseases included pulmonary aspergilloma (1.5%), pleural-related diseases (0.8%), hypersensitivity pneumonitis (0.8%), and obstructive sleep apnoea syndrome (0.6%). The study's annual trend showed a gradual increase in the number of respiratory cases, reaching a low point in 2020. Significant differences were found in the age and gender distribution of the top six respiratory diseases (p <0.001). Conclusions: This study provides valuable insights into the demographic and disease patterns of respiratory diseases in an outpatient setting, informing targeted prevention and treatment measures for these conditions

The changing culture of silviculture

Changing climates are altering the structural and functional components of forest ecosystems at an unprecedented rate. Simultaneously, we are seeing a diversification of public expectations on the broader sustainable use of forest resources beyond timber production. As a result, the science and art of silviculture needs to adapt to these changing realities. In this piece, we argue that silviculturists are gradually shifting from the application of empirically derived silvicultural scenarios to new sets of approaches, methods and practices, a process that calls for broadening our conception of silviculture as a scientific discipline. We propose a holistic view of silviculture revolving around three key themes: observe, anticipate and adapt. In observe, we present how recent advances in remote sensing now enable silviculturists to observe forest structural, compositional and functional attributes in near-real-time, which in turn facilitates the deployment of efficient, targeted silvicultural measures in practice that are adapted to rapidly changing constraints. In anticipate, we highlight the importance of developing state-of-the-art models designed to take into account the effects of changing environmental conditions on forest growth and dynamics. In adapt, we discuss the need to provide spatially explicit guidance for the implementation of adaptive silvicultural actions that are efficient, cost-effective and socially acceptable. We conclude by presenting key steps towards the development of new tools and practical knowledge that will ensure meeting societal demands in rapidly changing environmental conditions. We classify these actions into three main categories: reexamining existing silvicultural trials to identify key stand attributes associated with the resistance and resilience of forests to multiple stressors, developing technological workflows and infrastructures to allow for continuous forest inventory updating frameworks, and implementing bold, innovative silvicultural trials in consultation with the relevant communities where a range of adaptive silvicultural strategies are tested. In this holistic perspective, silviculture can be defined as the science of observing forest condition and anticipating its development to apply tending and regeneration treatments adapted to a multiplicity of desired outcomes in rapidly changing realities

Regulatory Cross-Talk Links Vibrio cholerae Chromosome II Replication and Segregation

There is little knowledge of factors and mechanisms for coordinating bacterial chromosome replication and segregation. Previous studies have revealed that genes (and their products) that surround the origin of replication (oriCII) of Vibrio cholerae chromosome II (chrII) are critical for controlling the replication and segregation of this chromosome. rctB, which flanks one side of oriCII, encodes a protein that initiates chrII replication; rctA, which flanks the other side of oriCII, inhibits rctB activity. The chrII parAB2 operon, which is essential for chrII partitioning, is located immediately downstream of rctA. Here, we explored how rctA exerts negative control over chrII replication. Our observations suggest that RctB has at least two DNA binding domains—one for binding to oriCII and initiating replication and the other for binding to rctA and thereby inhibiting RctB's ability to initiate replication. Notably, the inhibitory effect of rctA could be alleviated by binding of ParB2 to a centromere-like parS site within rctA. Furthermore, by binding to rctA, ParB2 and RctB inversely regulate expression of the parAB2 genes. Together, our findings suggest that fluctuations in binding of the partitioning protein ParB2 and the chrII initiator RctB to rctA underlie a regulatory network controlling both oriCII firing and the production of the essential chrII partitioning proteins. Thus, by binding both RctB and ParB2, rctA serves as a nexus for regulatory cross-talk coordinating chrII replication and segregation

DNA Adenine Methylation Is Required to Replicate Both Vibrio cholerae Chromosomes Once per Cell Cycle

DNA adenine methylation is widely used to control many DNA transactions, including replication. In Escherichia coli, methylation serves to silence newly synthesized (hemimethylated) sister origins. SeqA, a protein that binds to hemimethylated DNA, mediates the silencing, and this is necessary to restrict replication to once per cell cycle. The methylation, however, is not essential for replication initiation per se but appeared so when the origins (oriI and oriII) of the two Vibrio cholerae chromosomes were used to drive plasmid replication in E. coli. Here we show that, as in the case of E. coli, methylation is not essential for oriI when it drives chromosomal replication and is needed for once-per-cell-cycle replication in a SeqA-dependent fashion. We found that oriII also needs SeqA for once-per-cell-cycle replication and, additionally, full methylation for efficient initiator binding. The requirement for initiator binding might suffice to make methylation an essential function in V. cholerae. The structure of oriII suggests that it originated from a plasmid, but unlike plasmids, oriII makes use of methylation for once-per-cell-cycle replication, the norm for chromosomal but not plasmid replication

A next generation, pilot-scale continuous sterilization system for fermentation media

A new continuous sterilization system was designed, constructed, started up, and qualified for media sterilization for secondary metabolite cultivations, bioconversions, and enzyme production. An existing Honeywell Total Distributed Control 3000-based control system was extended using redundant High performance Process Manager controllers for 98 I/O (input/output) points. This new equipment was retrofitted into an industrial research fermentation pilot plant, designed and constructed in the early 1980s. Design strategies of this new continuous sterilizer system and the expanded control system are described and compared with the literature (including dairy and bio-waste inactivation applications) and the weaknesses of the prior installation for expected effectiveness. In addition, the reasoning behind selection of some of these improved features has been incorporated. Examples of enhancements adopted include sanitary heat exchanger (HEX) design, incorporation of a “flash” cooling HEX, on-line calculation of F(o) and R(o), and use of field I/O modules located near the vessel to permit low-cost addition of new instrumentation. Sterilizer performance also was characterized over the expected range of operating conditions. Differences between design and observed temperature, pressure, and other profiles were quantified and investigated

Longitudinal Changes of Fixation Location and Stability Within 12 Months in Stargardt Disease: ProgStar Report No. 12

Purpose: To investigate the natural history of Stargardt disease (STGD1) using fixation location and fixation stability. // Design: Multicenter, international, prospective cohort study. // Methods: Fixation testing was performed using the Nidek MP-1 microperimeter as part of the prospective, multicenter, natural history study on the Progression of Stargardt disease (ProgStar). A total of 238 patients with ABCA4-related STGD1 were enrolled at baseline (bilateral enrollment in 86.6%) and underwent repeat testing at months 6 and 12. // Results: Outcome measures included the distance of the preferred retinal locus from the fovea (PRL) and the bivariate contour ellipse area (BCEA). After 12 months of follow-up, the change in the eccentricity of the PRL from the anatomic fovea was −0.0014 degrees (95% confidence interval [CI], −0.27 degrees, 0.27 degrees; P = .99). The deterioration in the stability of fixation as expressed by a larger BCEA encompassing 1 standard deviation of all fixation points was 1.21 degrees squared (deg2) (95% CI, −1.23 deg2, 3.65 deg2; P = .33). Eyes with increases and decreases in PRL eccentricity and/or BCEA values were observed. // Conclusions: Our observations point to the complexity of fixation parameters. The association of increasingly eccentric and unstable fixation with longer disease duration that is typically found in cross-sectional studies may be countered within individual patients by poorly understood processes like neuronal adaptation. Nevertheless, fixation parameters may serve as useful secondary outcome parameters in selected cases and for counseling patients to explain changes to their visual functionality

Statistics of VHE γ -rays in temporal association with radio giant pulses from the Crab pulsar

Aims. The aim of this study is to search for evidence of a common emission engine between radio giant pulses (GPs) and very-high-energy (VHE, E  >   100 GeV) γ-rays from the Crab pulsar. Methods. We performed 16 h of simultaneous observations of the Crab pulsar at 1.4 GHz with the Effelsberg radio telescope and the Westerbork Synthesis Radio Telescope (WSRT), and at energies above 60 GeV we used the Major Atmospheric Gamma-ray Imaging Cherenkov (MAGIC) telescopes. We searched for a statistical correlation between the radio and VHE γ-ray emission with search windows of different lengths and different time lags to the arrival times of a radio GP. A dedicated search for an enhancement in the number of VHE γ-rays correlated with the occurrence of radio GPs was carried out separately for the P1 and P2 phase ranges, respectively. Results. In the radio data sample, 99444 radio GPs were detected. We find no significant correlation between the GPs and VHE photons in any of the search windows. Depending on phase cuts and the chosen search windows, we find upper limits at a 95% confidence level on an increase in VHE γ-ray events correlated with radio GPs between 7% and 61% of the average Crab pulsar VHE flux for the P1 and P2 phase ranges, respectively. This puts upper limits on the flux increase during a radio GP between 12% and 2900% of the pulsed VHE flux, depending on the search window duration and phase cuts. This is the most stringent upper limit on a correlation between γ-ray emission and radio GPs reported so far

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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