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Proton therapy is of great interest to pediatric cancer patients because of its optimal depth dose distribution. In view of healthy tissue damage and the increased risk of secondary cancers, we investigated DNA damage induction and repair of radiosensitive hematopoietic stem and progenitor cells (HSPCs) exposed to therapeutic proton and photon irradiation due to their role in radiation-induced leukemia. Human CD34 + HSPCs were exposed to 6 MV X-rays, mid- and distal spread-out Bragg peak (SOBP) protons at doses ranging from 0.5 to 2 Gy. Persistent chromosomal damage was assessed with the micronucleus assay, while DNA damage induction and repair were analyzed with the γ-H2AX foci assay. No differences were found in induction and disappearance of γ-H2AX foci between 6 MV X-rays, mid- and distal SOBP protons at 1 Gy. A significantly higher number of micronuclei was found for distal SOBP protons compared to 6 MV X-rays and mid- SOBP protons at 0.5 and 1 Gy, while no significant differences in micronuclei were found at 2 Gy. In HSPCs, mid-SOBP protons are as damaging as conventional X-rays. Distal SOBP protons showed a higher number of micronuclei in HSPCs depending on the radiation dose, indicating possible changes of the in vivo biological response., (© 2023. Springer Nature Limited.)

Objective: To update the state of the art regarding the acquisition of spinal high-velocity low-amplitude psychomotor skills competency among chiropractors and chiropractic students., Methods: Available electronic articles from 5 databases, published between June 2015 and August 2020, were obtained. Eligible studies underwent methodological quality assessments using the Joanna Briggs Institute Critical Appraisal Checklists and Cochrane Collaboration's Risk of Bias Tools., Results: Fourteen critically appraised studies were identified, including 10 cohort studies and 4 randomized controlled trials. There was no literature excluded due to high risk of bias. The type of augmented devices included a mannequin on a force platform, a computer-connected device, a human analogue mannequin, and a 3-dimensional electrogoniometer with an instrumented spatial linkage., Conclusion: The use of augmented feedback devices such as human analogue mannequins with force-sensing table technology and computer-connected devices is potentially beneficial in the chiropractic curricula and may facilitate student learning and improvement of spinal manipulation. More studies are required to determine whether psychomotor skill aids translate directly into raised competency levels in novice clinicians., (© 2023 Association of Chiropractic Colleges.)

The radiosensitivity of haematopoietic stem and progenitor cells (HSPCs) to neutron radiation remains largely underexplored, notwithstanding their potential role as target cells for radiation-induced leukemogenesis. New insights are required for radiation protection purposes, particularly for aviation, space missions, nuclear accidents and even particle therapy. In this study, HSPCs (CD34 + CD38 + cells) were isolated from umbilical cord blood and irradiated with 60 Co γ-rays (photons) and high energy p(66)/Be(40) neutrons. At 2 h post-irradiation, a significantly higher number of 1.28 ± 0.12 γ-H2AX foci/cell was observed after 0.5 Gy neutrons compared to 0.84 ± 0.14 foci/cell for photons, but this decreased to similar levels for both radiation qualities after 18 h. However, a significant difference in late apoptosis was observed with Annexin-V + /PI + assay between photon and neutron irradiation at 18 h, 43.17 ± 6.10% versus 55.55 ± 4.87%, respectively. A significant increase in MN frequency was observed after both 0.5 and 1 Gy neutron irradiation compared to photons illustrating higher levels of neutron-induced cytogenetic damage, while there was no difference in the nuclear division index between both radiation qualities. The results point towards a higher induction of DNA damage after neutron irradiation in HSPCs followed by error-prone DNA repair, which contributes to genomic instability and a higher risk of leukemogenesis., (© 2021. The Author(s).)

Background: Tuberculosis remains a global health challenge, with early diagnosis key to its reduction. Face-mask sampling detects exhaled Mycobacterium tuberculosis. We aimed to investigate bacillary output from patients with pulmonary tuberculosis and to assess the potential of face-mask sampling as a diagnostic method in active case-finding., Methods: We did a 24-h longitudinal study in patients from three hospitals in Pretoria, South Africa, with microbiologically confirmed pulmonary tuberculosis. Patients underwent 1 h of face-mask sampling eight times over a 24-h period, with contemporaneous sputum sampling. M tuberculosis was detected by quantitative PCR. We also did an active case-finding pilot study in inhabitants of an informal settlement near Pretoria. We enrolled individuals with symptoms of tuberculosis on the WHO screening questionnaire. Participants provided sputum and face-mask samples that were tested with the molecular assay Xpert MTB/RIF Ultra. Sputum-negative and face-mask-positive individuals were followed up prospectively for 20 weeks by bronchoscopy, PET-CT, and further sputum analysis to validate the diagnosis., Findings: Between Sept 22, 2015, and Dec 3, 2015, 78 patients with pulmonary tuberculosis were screened for the longitudinal study, of whom 24 completed the study (20 had HIV co-infection). M tuberculosis was detected in 166 (86%) of 192 face-mask samples and 38 (21%) of 184 assessable sputum samples obtained over a 24-h period. Exhaled M tuberculosis output showed no diurnal pattern and did not associate with cough frequency, sputum bacillary content, or chest radiographic disease severity. On May 16, 2018, 45 individuals were screened for the prospective active case-finding pilot study, of whom 20 had tuberculosis symptoms and were willing to take part. Eight participants were diagnosed prospectively with pulmonary tuberculosis, of whom six were exclusively face-mask positive at screening. Four of these participants (three of whom were HIV-positive) had normal findings on chest radiography but had treatment-responsive early tuberculosis-compatible lesions on PET-CT scans, with Xpert-positive sputum samples after 6 weeks., Interpretation: Face-mask sampling offers a highly efficient and non-invasive method for detecting exhaled M tuberculosis, informing the presence of active infection both with greater consistency and at an earlier disease stage than with sputum samples. The approach shows potential for diagnosis and screening, particularly in difficult-to-reach communities., Funding: Wellcome Trust, CARA (Council for At-Risk Academics), University of Leicester, the UK Medical Research Council, and the National Institute for Health Research. VIDEO ABSTRACT., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The lack of information on how biological systems respond to low-dose and low dose-rate exposures makes it difficult to accurately assess the carcinogenic risks. This is of critical importance to space radiation, which remains a serious concern for long-term manned space exploration. In this study, the γ-H2AX foci assay was used to follow DNA double-strand break (DSB) induction and repair following exposure to neutron irradiation, which is produced as secondary radiation in the space environment. Human lymphocytes were exposed to high dose-rate (HDR: 0.400 Gy/min) and low dose-rate (LDR: 0.015 Gy/min) p (66)/Be(40) neutrons. DNA DSB induction was investigated 30 min post exposure to neutron doses ranging from 0.125 to 2 Gy. Repair kinetics was studied at different time points after a 1 Gy neutron dose. Our results indicated that γ-H2AX foci formation was 40% higher at HDR exposure compared to LDR exposure. The maximum γ-H2AX foci levels decreased gradually to 1.65 ± 0.64 foci/cell (LDR) and 1.29 ± 0.45 (HDR) at 24 h postirradiation, remaining significantly higher than background levels. This illustrates a significant effect of dose rate on neutron-induced DNA damage. While no significant difference was observed in residual DNA damage after 24 h, the DSB repair half-life of LDR exposure was slower than that of HDR exposure. The results give a first indication that the dose rate should be taken into account for cancer risk estimations related to neutrons.

In the last 40 years only one new antitubercular drug has been approved, whilst resistance to current drugs, including rifampicin, is spreading. Here, we used the model organism Mycobacterium smegmatis to study mechanisms of phenotypic mycobacterial resistance, employing quantitative mass spectrometry-based proteomics to investigate the temporal effects of sub-lethal concentrations of rifampicin on the mycobacterial proteome at time-points corresponding to early response, onset of bacteriostasis and early recovery. Across 18 samples, a total of 3,218 proteins were identified from 31,846 distinct peptides averaging 16,250 identified peptides per sample. We found evidence that two component signal transduction systems (e.g. MprA/MprB) play a major role during initial mycobacterial adaptive responses to sub-lethal rifampicin and that, after dampening an initial SOS response, the bacteria supress the DevR (DosR) regulon and also upregulate their transcriptional and translational machineries. Furthermore, we found a co-ordinated dysregulation in haeme and mycobactin synthesis. Finally, gradual upregulation of the M. smegmatis-specific rifampin ADP-ribosyl transferase was observed which, together with upregulation of transcriptional and translational machinery, likely explains recovery of normal growth. Overall, our data indicates that in mycobacteria, sub-lethal rifampicin triggers a concerted phenotypic response that contrasts significantly with that observed at higher antimicrobial doses.

The Mycobacterium tuberculosis bacillus has a number of unique features that make it a particularly effective human pathogen. Although genomic analysis has added to our current understanding of the molecular basis by which M. tuberculosis damages its host, proteomics may be better suited to describe the dynamic interactions between mycobacterial and host systems that underpin this disease. The M. tuberculosis proteome has been investigated using proteomics for over a decade, with increasingly sophisticated mass spectrometry technology and sensitive methods for comparative proteomic profiling. Deeper coverage of the M. tuberculosis proteome has led to the identification of hundreds of putative virulence determinants, as well as an unsurpassed coverage of post-translational modifications. Proteomics is therefore uniquely poised to contribute to our understanding of this pathogen, which may ultimately lead to better management of the disease.

Introduction: Tuberculosis (TB) is the leading cause of death worldwide from a single infectious agent. Bacillus Calmette-Guérin (BCG), the only licensed vaccine, provides limited protection. Controlled human infection models (CHIMs) are useful in accelerating vaccine development for pathogens with no correlates of protection; however, the need for prolonged treatment makes Mycobacterium tuberculosis an unethical challenge agent. Aerosolised BCG provides a potential safe surrogate of infection. A CHIM in BCG-vaccinated as well as BCG-naïve individuals would allow identification of novel BCG-booster vaccine candidates and facilitate CHIM studies in populations with high TB endemicity. The purpose of this study was to evaluate the safety and utility of an aerosol BCG CHIM in historically BCG-vaccinated volunteers. Methods: There were 12 healthy, historically BCG-vaccinated UK adults sequentially enrolled into dose-escalating groups. The first three received 1 × 104 CFU aerosol BCG Danish 1331 via a nebuliser. After safety review, subsequent groups received doses of 1 × 105 CFU, 1 × 106 CFU, or 1 × 107 CFU. Safety was monitored through self-reported adverse events (AEs), laboratory tests, and lung function testing. Immunology blood samples were taken pre-infection and at multiple timepoints post-infection. A bronchoalveolar lavage (BAL) taken 14 days post-infection was analysed for presence of live BCG. Results: No serious AEs occurred during the study. Solicited systemic and respiratory AEs were frequent in all groups, but generally short-lived and mild in severity. There was a trend for more reported AEs in the highest-dose group. No live BCG was detected in BAL from any volunteers. Aerosol BCG induced potent systemic cellular immune responses in the highest-dose group 7 days post-infection. Discussion: Aerosol BCG infection up to a dose of 1 × 107 CFU was well-tolerated in historically BCG-vaccinated healthy, UK adults. No live BCG was detected in the BAL fluid 14 days post-infection despite potent systemic responses, suggesting early clearance. Further work is needed to expand the number of volunteers receiving BCG via the aerosol route to refine and establish utility of this aerosol BCG CHIM. Clinical trial registration: https://clinicaltrials.gov/ , identifier NCT04777721. [ABSTRACT FROM AUTHOR]

Background: Spinal manipulative therapy (SMT) is a guideline-recommended care for musculoskeletal pain taught in various undergraduate programs. Visual feedback through force-sensing tables can improve modulation of SMT force–time characteristics and, potentially, students' confidence, both factors important for clinical competence and patient outcomes. However, it is unclear if a link exists between students' confidence and ability in SMT force–time modulation. We aim to investigate this relationship and whether it was moderated by experience. Methods: This cross-sectional study recruited first- to third-year Canadian Memorial Chiropractic College students. Participants provided information about their confidence in performing SMT using different impulse forces of 200N, 400N, and 800N with a pre-established pre-load and a time-to-peak force < 150ms. SMT impulse forces of 200N, 400N, and 800N were targeted on a Human Analogue Mannequin positioned prone on a force-sensing table. We described the confidence levels and SMT force–time characteristics and assessed their association using linear mixed models. We re-ran the models interacting with SMT experience. The order of the three SMT impulse forces was randomly performed. Participants and outcome assessors were blinded to force–time characteristics recordings. Results: One-hundred-and-forty-nine participants provided usable data. Participants were confident in delivering 200N and 400N impulse forces. However, confidence decreased for 800N forces. Accordingly, participants performed impulse forces close to the 200N and 400N but had difficulty accurately modulating to 800N forces. A positive association was found between confidence and the ability to modulate their force–time characteristics, especially keeping the same pre-load force, keeping the time to peak force < 150ms, and providing the 800N impulse force. This association was not moderated by experience. Conclusions: Students were more confident in their abilities to perform lower SMT forces but lacked confidence in their abilities to perform higher (800N) forces. This aligned with their skills, as many struggled to apply 800N force. However, students who had higher confidence levels generally performed better overall. There was substantial variability in SMT force–time characteristics, which may have implications for adverse events and patient satisfaction. Some of this variability could be attributed to students' confidence. Thus, further investigations are necessary in undergraduate settings to implement and optimize these findings. Registration: https://osf.io/6f7d5 [ABSTRACT FROM AUTHOR]

In 2014, the World Health Organisation (WHO) published target product profiles (TPP) for development of novel tuberculosis (TB) diagnostics. One of the key highlights is the need for point-of-care non-sputum-based tests capable of detecting all forms of TB through identification of characteristic biomarkers or biosignatures. Compared to the limitations associated with sputum-based TB tests, non-sputum samples are easy to collect, non-invasive, with potential to improve TB diagnosis among children and among people living with HIV/AIDS (PLHIV). This review gives an overview of the existing evidence on TB diagnostic studies of non-sputum-based samples collected non-invasively from or through the oral–gastrointestinal tract (GI) and nasal pharynx regions of humans and the biomarkers detected. We further summarized evidence of these biomarkers and sample types from research done in paediatric and PLHIV. The review identified; saliva, cough aerosols, oral swabs, oral wash, dental plaque, tongue swabs, face mask sampling, exhaled breath, and stool, as the non-sputum samples investigated. These biomarkers can be categorized into Deoxyribose Nucleic Acid (DNA), Ribonucleic Acid (RNA), inflammatory, antigen–antibody, volatile and non-volatile compounds, microbiome and microbiota. The biomarkers identified were derived both from the host and pathogen. Similar biomarkers were identified in the general population, children and among PLHIV. These biomarkers have been detected by either already approved simple point of care or sophisticated devices. Differences in methodology and sample types investigated, small sample size of children and PLHIV populations, bias due to confounding factors, were some of the identified challenges in these studies. There is need to conduct larger and standardized multi centre studies to evaluate non-sputum-based biomarker-based tests in children and PLHIV. [ABSTRACT FROM AUTHOR]

Rapid and accurate point-of-care (POC) tuberculosis (TB) diagnostics are crucial to bridge the TB diagnostic gap. Leveraging recent advancements in COVID-19 diagnostics, we explored adapting commercially available POC SARS-CoV-2 tests for TB diagnosis in line with the World Health Organization (WHO) target product profiles (TPPs). A scoping review was conducted following PRISMA-ScR guidelines to systematically map POC antigen and molecular SARS-CoV-2 diagnostic tests potentially meeting the TPPs for TB diagnostic tests for peripheral settings. Data were gathered from PubMed/MEDLINE, bioRxiv, medRxiv, publicly accessible in vitro diagnostic test databases, and developer websites up to 23 November 2022. Data on developer attributes, operational characteristics, pricing, clinical performance, and regulatory status were charted using standardized data extraction forms and evaluated with a standardized scorecard. A narrative synthesis of the data is presented. Our search yielded 2003 reports, with 408 meeting eligibility criteria. Among these, we identified 66 commercialized devices: 22 near-POC antigen tests, 1 POC molecular test, 31 near-POC molecular tests, and 12 low-complexity molecular tests potentially adaptable for TB. The highest-scoring SARS-CoV-2 diagnostic tests were the near-POC antigen platform LumiraDx (Roche, Basel, Switzerland), the POC molecular test Lucira Check-It (Pfizer, New York, NY, USA), the near-POC molecular test Visby (Visby, San Jose, CA, USA), and the low-complexity molecular platform Idylla (Biocartis, Lausanne, Switzerland). We highlight a diverse landscape of commercially available diagnostic tests suitable for potential adaptation to peripheral TB testing. This work aims to bolster global TB initiatives by fostering stakeholder collaboration, leveraging SARS-CoV-2 diagnostic technologies for TB, and uncovering new commercial avenues to tackle longstanding challenges in TB diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: Hadrons, i.e. particles that are heavier than electrons, are playing an increasingly important role in radiation oncology. Due to the high investment costs for the necessary infrastructure, this option is only available in specialized centers. Methods: This article describes some of the physical properties that make hadrons attractive for external beam radiation therapy (EBRT), but also some of the challenges that need to be considered. Results: The importance of linear energy transfer for biological effects is discussed. Conclusions: In addition to the use of charged particles, the importance of neutrons for radiotherapy is also highlighted, in particular the properties of boron neutron capture therapy (BNCT), which open up completely new possibilities for the further development of EBRT. [ABSTRACT FROM AUTHOR]

In the United States, the Federal Aviation Administration has officially classified flight crews (FC) consisting of commercial pilots, cabin crew, or flight attendants as "radiation workers" since 1994 due to the potential for cosmic ionizing radiation (CIR) exposure at cruising altitudes originating from solar activity and galactic sources. Several epidemiological studies have documented elevated incidence and mortality for several cancers in FC, but it has not yet been possible to establish whether this is attributable to CIR. CIR and its constituents are known to cause a myriad of DNA lesions, which can lead to carcinogenesis unless DNA repair mechanisms remove them. But critical knowledge gaps exist with regard to the dosimetry of CIR, the role of other genotoxic exposures among FC, and whether possible biological mechanisms underlying higher cancer rates observed in FC exist. This review summarizes our understanding of the role of DNA damage and repair responses relevant to exposure to CIR in FC. We aimed to stimulate new research directions and provide information that will be useful for guiding regulatory, public health, and medical decision-making to protect and mitigate the risks for those who travel by air. [ABSTRACT FROM AUTHOR]

In the soundscape approach, environmental sounds are not considered noise, but as a source and as a component of the spatial planning and design process. It is necessary to evaluate the soundscape in urban spaces in a multifaceted and holistic manner, together with many factors such as physical, social, cultural, psychological, architectural, and so on. In this study, it is aimed to develop an estimation model that will allow the stages that take a long time to progress faster and more systematically in the multifaceted evaluation of the sound environment pleasantness levels of the users in urban spaces with the soundscape approach. For the model's quantitative data, sound quality metrics (loudness, sharpness, roughness) obtained from binaural sound recordings were used. The fuzzy logic estimation model is constructed by using Simple Membership Functions and the Fuzzy Rules Generation Technique (SMRGT) method, considering the characteristics of users and the survey area. In the model, it was possible to convey user experiences, and a simple approach that could be expressed numerically and understood was obtained with the fiction created with verbal concepts. Flexibility is allowed to diversify quantitative and qualitative metrics. The model has been tested with the case study performed with the users. As a result of the study, a close relationship was determined between the model outputs and the subjective data of the users. The efficiency ratios of other variables (age, gender, reasons for coming to the region, frequency of visit, duration of stay) belonging to users not included in the model were also determined. In this study, it has been revealed that the level of pleasantness of the sound environment in urban spaces should be evaluated not only in terms of quantitative data but also on the characteristics of the spaces and users. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) remains a major infectious disease partly due to the lack of an effective vaccine. Therefore, developing new and more effective TB vaccines is crucial for controlling TB. Mycobacterium tuberculosis (M. tuberculosis) usually parasitizes in macrophages; therefore, cell-mediated immunity plays an important role. The maintenance of memory T cells following M. tuberculosis infection or vaccination is a hallmark of immune protection. This review analyzes the development of memory T cells during M. tuberculosis infection and vaccine immunization, especially on immune memory induced by BCG and subunit vaccines. Furthermore, the factors affecting the development of memory T cells are discussed in detail. The understanding of the development of memory T cells should contribute to designing more effective TB vaccines and optimizing vaccination strategies. [ABSTRACT FROM AUTHOR]

A fundamental challenge for personalized medicine is to capture enough of the complexity of an individual patient to determine an optimal way to keep them healthy or restore their health. This will require personalized computational models of sufficient resolution and with enough mechanistic information to provide actionable information to the clinician. Such personalized models are increasingly referred to as medical digital twins. Digital twin technology for health applications is still in its infancy, and extensive research and development is required. This article focuses on several projects in different stages of development that can lead to specific--and practical-medical digital twins or digital twin modeling platforms. It emerged from a two-day forum on problems related to medical digital twins, particularly those involving an immune system component. Open access video recordings of the forum discussions are available. [ABSTRACT FROM AUTHOR]

DNA damage is induced by both endogenous and exogenous factors. Repair of DNA double-strand break (DSB), a serious damage that threatens genome stability, decreases with senescence. However, the molecular mechanisms underlying the decline in DNA repair capacity during senescence remain unclear. We performed immunofluorescence staining for phosphorylated histone H2AX (γ-H2AX) in normal human fetal lung fibroblasts and human skin fibroblasts of different ages after chronic irradiation (total dose, 1 Gy; dose rate, 1 Gy/day) to investigate the effect of cellular senescence and organismal aging on DSB repair. Accumulation of DSBs was observed with cellular senescence and organismal aging, probably caused by delayed DSB repair. Importantly, the formation of γ-H2AX foci, an early event in DSB repair, is delayed with cellular senescence and organismal aging. These results suggest that the delay in γ-H2AX focus formation might delay the overall DSB repair. Interestingly, immediate γ-H2AX foci formation was suppressed in cells with senescence-associated heterochromatin foci (SAHF). To investigate the relationship between the γ-H2AX focus formation and SAHF, we used LiCl to relax the SAHFs, followed by irradiation. We demonstrated that LiCl rescued the delayed γ-H2AX foci formation associated with cellular senescence. This indicates that SAHF interferes with γ-H2AX focus formation and inhibits DSB repair in radiation-induced DSB. Our results suggest that therapeutic targeting of SAHFs have potential to resolve DSB repair dysfunction associated with cellular senescence. [ABSTRACT FROM AUTHOR]

Congenital hearing loss is the most common birth defect, estimated to affect 2–3 in every 1000 births, with ~50–60% of those related to genetic causes. Technological advances enabled the identification of hundreds of genes related to hearing loss (HL), with important implications for patients, their families, and the community. Despite these advances, in Latin America, the population with hearing loss remains underdiagnosed, with most studies focusing on a single locus encompassing the GJB2/GJB6 genes. Here we discuss how current and emerging genetic knowledge has the potential to alter the approach to diagnosis and management of hearing loss, which is the current situation in Latin America, and the barriers that still need to be overcome. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a primary malignancy of the central nervous system and is classified as a grade IV astrocytoma by the World Health Organization (WHO). Although GBM rarely metastasizes, its prognosis remains poor. Moreover, the standard treatment for GBM, temozolomide (TMZ), is associated with chemoresistance, which is a major factor behind GBM-related deaths. Investigating drugs with repurposing potential in the context of GBM is worthwhile to bypass lengthy bench-to-bedside research. The field of omics has garnered significant interest in scientific research because of its potential to delineate the intricate regulatory network underlying tumor development. In particular, proteomic and metabolomic analyses are powerful approaches for the investigation of metabolic enzymes and intermediate metabolites since they represent the functional end of the cancer phenotype. We chose two of the most widely prescribed anticancer drugs, cisplatin and paclitaxel. To our knowledge, the current literature lacks studies examining their effects on metabolic and proteomic alterations in GBM. We employed the mass spectrometry technological platform 'UHPLC-Q-TOF-MS/MS' to examine the changes in the proteome and metabolome profiles of the U87 cell line with defined concentrations of cisplatin and/or paclitaxel via an untargeted approach. A total of 1,419 distinct proteins and 90 metabolites were generated, and subsequent analysis was performed. We observed that upon treatment with cisplatin (9.5 μM), U87 cells exhibited apparent efforts to cope with this exogenous stressor, understanding the effect of paclitaxel (5.3 μM) on altering the transport machinery of the cell, and how the combination of cisplatin and/or paclitaxel suggests potential interactions with promising benefits in GBM therapeutics. Our research provides a detailed map of alterations in response to cisplatin and paclitaxel treatment, provides crucial insights into the molecular basis of their action, and paves the way for further research to identify molecular targets for this elusive malignancy. [ABSTRACT FROM AUTHOR]

Rapid industrialization and unplanned urbanization have significantly increased environmental pollution. These human behaviors have resulted in massive waste discharges into the environment. As a result, organic and inorganic contaminants, including heavy metals, have accumulated in surface and groundwater. Heavy metals are highly carcinogenic and deadly. Heavy metal removal from drinking water has always been difficult. Conventional water treatment procedures could be more efficient, wasteful of energy, and generate massive amounts of harmful waste. In this initiative, researchers created a bio-based adsorption technology for removing heavy metal ions from polluted water. Nano celluloses (NCs) as biosorbents have sparked considerable attention due to their unique properties, such as the presence of several -OH groups on their surface, allowing the insertion of chemical moieties, a substantial specific surface area, strong mechanical properties, recyclability, and biodegradability. This review paper goes into great detail regarding the ways of producing Nano cellulose and its essential qualities. Many factors influence the use of NCbased adsorbents in water treatment systems, including synthesis pathways, functionalization of the surface, specific surface area, regeneration capacity, and reusability. Recent advances in bio-sorbent synthesis have prompted using bio-derived NC-based adsorbents in water treatment methods. This study also demonstrates that utilizing the potential for agricultural wastes, specifically sugarcane bagasse (SCB), as a precursor for Nano celluloses represents a sustainable approach, namely the conversion of low-value waste into a specific high-value product and its use in wastewater treatment. [ABSTRACT FROM AUTHOR]

Apart from being preventable and treatable, tuberculosis is the deadliest bacterial disease afflicting humankind owing to its ability to evade host defence responses, many of which are controlled by epigenetic mechanisms. Here, we report the temporal dynamics of the proteome of macrophage-like host cells after infecting them for 6, 18, 30, and 42 h with two laboratory strains (H37Ra and H37Rv) and two clinical strains (BND433 and JAL2287) of Mycobacterium tuberculosis (MTB). Using SWATH-MS, the proteins characterized at the onset of infection broadly represented oxidative stress and cell cytoskeleton processes. Intermediary and later stages of infection are accompanied by a reshaping of the combination of proteins implicated in histone stability, gene expression, and protein trafficking. This study provides strain-specific and time-specific variations in the proteome of the host, which might further the development of host-directed therapeutics and diagnostic tools against the pathogen. Also, our findings accentuate the importance of proteomic tools in delineating the complex recalibration of the host defence enabled as an effect of MTB infection. To the best of our knowledge, this is the first comprehensive proteomic account of the host response to avirulent and virulent strains of MTB at different time periods of the life span of macrophage-like cells. The mass spectrometry proteomics data have been deposited in the ProteomeXchange Consortium via the PRIDE repository with the dataset identifier PXD022352. [ABSTRACT FROM AUTHOR]

Nose masks are widely worn for protection against respiratory pathogens, including SARS-CoV-2. They have been reported as possible substrates for viral sampling and testing for COVID-19 but, evaluations have so far been purposive; involving individuals known to have the infection and using improved materials on the nose masks to trap the virus. We investigated the feasibility of using the regular 3-ply surgical masks and, voluntary coughing as a mode of particle expulsion for detecting SARS-CoV-2 infections in a cross-sectional study at Ghana's first COVID-19 testing reference laboratory, the Noguchi Memorial Institute for Medical Research, University of Ghana. Paired samples of naso-oropharyngeal swabs and nose masks already worn by 103 consenting adult participants (retro masks) were collected. Participants were also required to produce three strong coughs into a newly supplied sterile surgical nose mask. Pre-wetted swabs in Viral Transport Media (VTM) were used in swabbing the inner lining of each nose mask. The swabs used were then stored in VTM to maintain the integrity of the samples. PCR results of SARS-CoV-2 detection from the nose masks were compared to those from naso-oropharyngeal swabs ('gold-standard'). Out of the 103 participants tested with all three methods, 66 individuals sampled with naso-oropharyngeal swabs were detected as positive, and the retro and new masks matched 9 and 4, respectively. Only 3 individuals were positive across all three sampling methods accessed. The retro nose masks performed better in matching the gold-standard results than the new mask + coughing method, with 90% vs 80% sensitivity, positive predictive value of 13.6% vs 6%, and a weak but significant linear relationship (adj. R2 = 0.1; P = 0.0004). Importantly, we also show that the nose masks would work for sampling whether individuals are symptomatic or asymptomatic since gold-standard PCR cycling threshold (Ct) values for positive individuals did not differ between the two groups (P< 0.05). We recommend including features such as talking during participant engagement, use of a spontaneous cough inducer and increased coughing bouts > 3, to improve the performance of sterile nose masks for SARS-CoV-2 detection. [ABSTRACT FROM AUTHOR]

Abstract: Boron neutron capture therapy (BNCT) is an ideal binary targeted radiotherapy for treating refractory tumors. An accelerator-based BNCT (AB-BNCT) neutron source has attracted more and more attention due to its advantages such as higher neutron yield in the keV energy region, less gamma radiation, and higher safety. In addition to 10 B, neutrons also react with other elements in the treatment room during BNCT to produce many activation products. Due to the long half-life of some activation products, there will be residual radiation after the end of treatment and the shutdown of the accelerator, which has adverse effects on radiation workers. Therefore, the ambient dose equivalent rate in the treatment room needs to be evaluated. The AB-BNCT neutron source model proposed by Li is studied in this paper. Based on the Monte Carlo method, the Geant4 platform was used to simulate the dose induced by radionuclides near the Beam Shaping Assembly (BSA) of the source. It is concluded that the concrete wall contributed the most to the radiation dose. The dose rate of 2.45 μSv h -1 after 13 min of shutdown meets the dose rate limit of 2.5 μSv h -1 , at which point it is safe for workers to enter the treatment room area., (Copyright © 2024 Health Physics Society.)

High energy electron scattering of liquid water (H2O) at near-ambient temperature and pressure was performed in a transmission electron microscope (TEM) to determine the radial distribution of water, which provides information on intra- and intermolecular spatial correlations. A recently developed environmental liquid cell enables formation of a stable water layer, the thickness of which is readily controlled by pressure and flow rate adjustments of a humid air stream passing between two silicon nitride (Si3N4) membranes. The analysis of the scattering data is adapted from the x-ray methodology to account for multiple scattering in the H2O:Si3N4 sandwich layer. For the H2O layer, we obtain oxygen–oxygen (O–O) and oxygen–hydrogen (O–H) peaks at 2.84 Å and 1.83 Å, respectively, in good agreement with values in the literature. This demonstrates the potential of our approach toward future studies of water-based physics and chemistry in TEMs or electron probes of structural dynamics. [ABSTRACT FROM AUTHOR]

Background: Pulmonary tuberculosis (PTB) diagnosis relies on sputum examination, a challenge in sputum-scarce patients. Alternative non-invasive sampling methods such as face mask sampling (FMS) have been proposed. Objective: To evaluate the value of FMS for PTB diagnosis by assessing its agreement with sputum samples processed by GeneXpert MTB/RIF (Ultra)(Xpert) testing, and describe FMS sensitivity and specificity. Methods: This was a prospective study conducted at the Carrière TB clinic in Guinea. Presumptive TB patients willing to participate were asked to wear a surgical mask containing a polyvinyl alcohol (PVA) strip for thirty minutes. Subsequently, two spot sputum samples were collected, of which one was processed by microscopy on site and the other by Xpert in Guinea's National Reference Laboratory of Mycobacteriology (LNRM). The first 30 FMS were processed at the Supranational Reference Laboratory in Antwerp, Belgium, and the following 118 FMS in the LNRM. Results: One hundred fifty patients participated, of whom 148 had valid results for both mask and sputum. Sputum smear microscopy was positive for 47 (31.8%) patients while sputum-Xpert detected MTB in 54 (36.5%) patients. Among the 54 patients testing sputum-Xpert positive, 26 (48.1%) yielded a positive FMS-Xpert result, while four sputum-Xpert negative patients tested positive for FMS and 90 patients were Xpert-negative for both sputum and mask samples, suggesting a moderate level of agreement (k-value of 0.47). The overall mask sensitivity was 48.1%, with 95.7% specificity. Conclusion: In our setting, Xpert testing on FMS did not yield a high level of agreement to sputum sample. [ABSTRACT FROM AUTHOR]

Background: Knowledge on predicting pulmonary tuberculosis (PTB) contagiosity in the hospital admission setting is limited. The objective was to assess clinical and radiological criteria to predict PTB contagiosity. Methods: Retrospective analysis of 7 clinical, 4 chest X-ray (CXR) and 5 computed tomography (CT) signs in 299 PTB patients admitted to an urban tertiary hospital from 2008 to 2016. If the acid fact bacilli stain was positive (AFB+) on admission, the case was considered high contagiosity. Results: Best predictors for high PTB contagiosity (AFB+) were haemoptysis (OR 4.33), cough (3.00), weight loss (2.96), cavitation in CT (2.75), cavitation in CXR (2.55), tree-in-bud-sign in CT (2.12), German residency of the patient (1.89), and abnormal auscultation findings (1.83). A previous TB infection reduced the risk of contagiosity statistically (0.40). Radiographic infiltrates, miliary picture, and pleural effusion were not helpful in predicting high or low contagiosity. 34% of all patients were clinically asymptomatic (20% of the highly contagious group, 50% of the low contagious group). Conclusion: Haemoptysis, cough and weight loss as well as cavitation and tree-in-bud sign in CXR/CT can be helpful to predict PTB contagiosity and to improve PTB management. [ABSTRACT FROM AUTHOR]

Forensic social workers are vulnerable to secondary traumatic stress due to their direct exposure to trauma narratives from sexually abused children. They face the unique challenge of distinguishing between their roles as expert witnesses and therapists. However, research on the risk factors for secondary traumatic stress in forensic social workers is frequently disregarded both internationally and in South Africa. The purpose of this study was to look at the effect of internal and external risk factors on secondary traumatic stress symptoms among forensic social workers. An all-inclusive voluntary sample method was used to include all trained forensic social workers with a master's degree in forensic practice who graduated from a recognised South African university between 2006 and 2019. The study used a quantitative cross-sectional descriptive design and data was collected using Google Forms, which was distributed via email. IBM SPSS version 27 was used to analyse the data. Internal factors such as race and relationship status as well as external factors such as clinical supervision, social support, and exposure to traumatic experiences were found to have varied effects on secondary traumatic stress symptoms in the study. [ABSTRACT FROM AUTHOR]

In recent years, wearable devices have been increasingly used to monitor people's health. This has helped healthcare professionals provide timely interventions to support their patients. In this study, we investigated how wearables help people manage stress. We conducted a scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) standard to address this question. We searched studies in Scopus, IEEE Explore, and Pubmed databases. We included studies reporting user evaluations of wearable-based strategies, reporting their impact on health or usability outcomes. A total of 6259 studies were identified, of which 40 met the inclusion criteria. Based on our findings, we identified that 21 studies report using commercial wearable devices; the most common are smartwatches and smart bands. Thirty-one studies report significant stress reduction using different interventions and interaction modalities. Finally, we identified that the interventions are designed with the following aims: (1) to self-regulate during stress episodes, (2) to support self-regulation therapies for long-term goals, and (3) to provide stress awareness for prevention, consisting of people's ability to recall, recognize and understand their stress. [ABSTRACT FROM AUTHOR]

Based on criminal court cases found in archives and newspapers, this article traces how the diagnosis of hysteria functioned in trials and Dutch forensic psychiatric practice c. 1885–1960. Informed by Science and Technology Studies and praxiography, hysteria is studied as a 'fire object'. It can make multiple relations with gender, which can be absent or present. This approach asks whether and how gender is important regarding hysteria. Gender only 'stuck' to hysteria in certain situations. In rape cases, hysteria took the form of lying and was connected to women. Although a woman's hysteria could be used as a reason to exonerate the male perpetrator's crime of murder, a man's hysteria never served to exculpate a female perpetrator of a crime. Signs on the body appeared to be very significant but did not suffice for a clear diagnosis. Inconsistencies during the psychiatric examination of the body therefore needed to be coordinated by pointing to other bodily symptoms, personal life stories, academic literature or logical reasoning. To analyse the ways hysteria functioned as a versatile fire object in the courtroom and pre‐trial investigation alerts us to hysteria's shapeshifting potential that might explain the power of the hysteria label in twentieth‐century medicine and culture. [ABSTRACT FROM AUTHOR]

Controlled Human Infection Models (CHIMs) involve deliberately exposing healthy human volunteers to a known pathogen, to allow the detailed study of disease processes and evaluate methods of treatment and prevention, including next generation vaccines. CHIMs are in development for both tuberculosis (TB) and Covid-19, but challenges remain in their ongoing optimisation and refinement. It would be unethical to deliberately infect humans with virulent Mycobacteria tuberculosis (M.tb), however surrogate models involving other mycobacteria, M.tb Purified Protein Derivative or genetically modified forms of M. tb either exist or are under development. These utilise varying routes of administration, including via aerosol, per bronchoscope or intradermal injection, each with their own advantages and disadvantages. Intranasal CHIMs with SARS-CoV-2 were developed against the backdrop of the evolving Covid-19 pandemic and are currently being utilised to both assess viral kinetics, interrogate the local and systemic immunological responses post exposure, and identify immune correlates of protection. In future it is hoped they can be used to assess new treatments and vaccines. The changing face of the pandemic, including the emergence of new virus variants and increasing levels of vaccination and natural immunity within populations, has provided a unique and complex environment within which to develop a SARS-CoV-2 CHIM. This article will discuss current progress and potential future developments in CHIMs for these two globally significant pathogens. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis is the causative agent of tuberculosis. M. tuberculosis can survive in a dormant state within the granuloma, avoiding the host-mounting immune attack. M. tuberculosis bacilli in this state show increased tolerance to antibiotics and stress conditions, and thus the transition of M. tuberculosis to the nonreplicating dormant state acts as an obstacle to tuberculosis treatment. M. tuberculosis in the granuloma encounters hostile environments such as hypoxia, nitric oxide, reactive oxygen species, low pH, and nutrient deprivation, etc., which are expected to inhibit respiration of M. tuberculosis. To adapt to and survive in respiration-inhibitory conditions, it is required for M. tuberculosis to reprogram its metabolism and physiology. In order to get clues to the mechanism underlying the entry of M. tuberculosis to the dormant state, it is important to understand the mycobacterial regulatory systems that are involved in the regulation of gene expression in response to respiration inhibition. In this review, we briefly summarize the information regarding the regulatory systems implicated in upregulation of gene expression in mycobacteria exposed to respiration-inhibitory conditions. The regulatory systems covered in this review encompass the DosSR (DevSR) two-component system, SigF partner switching system, MprBA-SigE-SigB signaling pathway, cAMP receptor protein, and stringent response. [ABSTRACT FROM AUTHOR]

A mask serves as a simple external barrier that protects humans from infectious particles from poor air conditions in the surrounding environment. As an important personal protective equipment (PPE) to protect our respiratory system, masks are able not only to filter pathogens and dust particles but also to sense, reflect or even respond to environmental conditions. This smartness is of particular interest among academia and industries due to its potential in disease detection, health monitoring and caring aspects. In this review, we provide an overlook of the current air filtration strategies used in masks, from structural designs to integrated functional modules that empower the mask's ability to sense and transfer physiological or environmental information to become smart. Specifically, we discussed recent developments in masks designed to detect macroscopic physiological signals from the wearer and mask-based disease diagnoses, such as COVID-19. Further, we propose the concept of next-generation smart masks and the requirements from material selection and function design perspectives that enable masks to interact and play crucial roles in health-caring wearables. [ABSTRACT FROM AUTHOR]

Salinity is a decisive abiotic factor that modulates the physiology of aquatic organisms. Salinity itself is modulated by various factors—most notably by anthropogenic factors. In coastal regions, increasing salinity is observed mostly due to the elevated rate of evaporation under high temperatures, especially under global warming. In addition, many other anthropogenic factors, climatic factors, chemicals, etc., also contribute to the changes in salinity in coastal water. Some of these include rainfall, regional warming, precipitation, moisture, thermohaline circulation, gaseous pollutants, dissolved chemicals, wind flow, and biocrusts. Salinity has been found to regulate the osmotic balance and, thus, can directly or indirectly influence the biomarkers of oxidative stress (OS) in aquatic organisms. Imbalances in OS potentially affect the growth, production, and reproduction of organisms; therefore, they are being studied in organisms of economic or aquacultural importance. Salinity-modulated OS and redox regulation as a function of phylum are covered in this review. The literature from 1960 to 2021 indicates that the altered OS physiology under changing salinity or in combination with other (anthropogenic) factors is species-specific, even within a particular phylum. Thus, knowing the response mechanisms of such organisms to salinity may be useful for the management of specific aquatic animals or their habitats. [ABSTRACT FROM AUTHOR]

To contribute new information to the pyrethroid pesticide α-cypermethrin toxicity profile, we evaluated its effects after oral administration to Wistar rats at daily doses of 2.186, 0.015, 0.157, and 0.786 mg/kg bw for 28 days. Evaluations were performed using markers of oxidative stress, cholinesterase (ChE) activities, and levels of primary DNA damage in plasma/whole blood and liver, kidney, and brain tissue. Consecutive exposure to α-cypermethrin affected the kidney, liver, and brain weight of rats. A significant increase in concentration of the thiobarbituric acid reactive species was observed in the brain, accompanied by a significant increase in glutathione peroxidase (GPx) activity. An increase in GPx activity was also observed in the liver of all α-cypermethrin-treated groups, while GPx activity in the blood was significantly lower than in controls. A decrease in ChE activities was observed in the kidney and liver. Treatment with α-cypermethrin induced DNA damage in the studied cell types at almost all of the applied doses, indicating the highest susceptibility in the brain. The present study showed that, even at very low doses, exposure to α-cypermethrin exerts genotoxic effects and sets in motion the antioxidative mechanisms of cell defense, indicating the potential hazards posed by this insecticide. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is one of the deadliest infectious diseases in the world; therefore, controlling TB epidemics is one of the main priorities of global public health. According to the priorities of the World Health Organization, developing and designing new vaccines are needed more than ever to control the spread of this disease. Meanwhile, efforts to produce new drugs against the infection can be effective for the treatment of the disease. Today, the only approved vaccine for TB prevention is Bacille Calmette -Guerin (widely known as BCG) which cannot provide immunity in adults. As a result, researchers have done many investigations in clinical development and pre - clinical trials to prepare new vaccines and to examine new candidates to replace or enhance BCG vaccine. This review investigates the history of BCG vaccine, its limitations as well as recent advances to improve its immunogenicity while reducing its side effects. Moreover, other TB vaccines along with new TB vaccine candidates in clinical trials are presented in this article. [ABSTRACT FROM AUTHOR]

Tuberculosis has affected humankind for thousands of years, but a deeper understanding of its cause and transmission only arose after Robert Koch discovered Mycobacterium tuberculosis in 1882. Valuable insight has been gained since, but the accumulation of knowledge has been frustratingly slow and incomplete for a pathogen that remains the number one infectious disease killer on the planet. Contrast that to the rapid progress that has been made in our understanding SARS-CoV-2 (the cause of COVID-19) aerobiology and transmission. In this Review, we discuss important historical and contemporary insights into M. tuberculosis transmission. Historical insights describing the principles of aerosol transmission, as well as relevant pathogen, host and environment factors are described. Furthermore, novel insights into asymptomatic and subclinical tuberculosis, and the potential role this may play in population-level transmission is discussed. Progress towards understanding the full spectrum of M. tuberculosis transmission in high-burden settings has been hampered by sub-optimal diagnostic tools, limited basic science exploration and inadequate study designs. We propose that, as a tuberculosis field, we must learn from and capitalize on the novel insights and methods that have been developed to investigate SARS-CoV-2 transmission to limit ongoing tuberculosis transmission, which sustains the global pandemic. [ABSTRACT FROM AUTHOR]

New tuberculosis (TB) diagnostics are at a crossroads: their development, evaluation, and implementation is severely damaged by resource diversion due to COVID-19. Yet several technologies, especially those with potential for non-invasive non-sputum-based testing, hold promise for efficiently triaging and rapidly confirming TB near point-of-care. Such tests are, however, progressing through the pipeline slowly and will take years to reach patients and health workers. Compellingly, such tests will create new opportunities for difficult-to-diagnose populations, including primary care attendees (all-comers in high burden settings irrespective of reason for presentation) and community members (with early stage disease or risk factors like HIV), many of whom cannot easily produce sputum. Critically, all upcoming technologies have limitations that implementers and health workers need to be cognizant of to ensure optimal deployment without undermining confidence in a technology that still offers improvements over the status quo. In this state-of-the-art review, we critically appraise such technologies for active pulmonary TB diagnosis. We highlight strengths, limitations, outstanding research questions, and how current and future tests could be used in the presence of these limitations and uncertainties. Among triage tests, CRP (for which commercial near point-of-care devices exist) and computer-aided detection software with digital chest X-ray hold promise, together with late-stage blood-based assays that detect host and/or microbial biomarkers; however, aside from a handful of prototypes, the latter category has a shortage of promising late-stage alternatives. Furthermore, positive results from new triage tests may have utility in people without TB; however, their utility for informing diagnostic pathways for other diseases is under-researched (most sick people tested for TB do not have TB). For confirmatory tests, few true point-of-care options will be available soon; however, combining novel approaches like tongue swabs with established tests like Ultra have short-term promise but first require optimizations to specimen collection and processing procedures. Concerningly, no technologies yet have compelling evidence of meeting the World Health Organization optimal target product profile performance criteria, especially for important operational criteria crucial for field deployment. This is alarming as the target product profile criteria are themselves almost a decade old and require urgent revision, especially to cater for technologies made prominent by the COVID-19 diagnostic response (e.g., at-home testing and connectivity solutions). Throughout the review, we underscore the importance of how target populations and settings affect test performance and how the criteria by which these tests should be judged vary by use case, including in active case finding. Lastly, we advocate for health workers and researchers to themselves be vocal proponents of the uptake of both new tests and those – already available tests that remain suboptimally utilized. [ABSTRACT FROM AUTHOR]

Concentrations of major ions in coal mine discharge waters and unconventional hydrocarbon produced waters derived from coal bed methane (CBM) production, are potentially harmful to freshwater ecosystems. Bicarbonate is a major constituent of produced waters from CBM and coal mining. However, little is known about the relative toxicity of differing ionic proportions, especially bicarbonate, found in these CBM waters. As all freshwater invertebrates tested are more acutely sensitive to sodium bicarbonate (NaHCO3) than sodium chloride (NaCl) or synthetic sea water, we tested the hypotheses that toxicity of CBM waters are driven by bicarbonate concentration, and waters containing a higher proportion of bicarbonate are more toxic to freshwater invertebrates than those with less bicarbonate. We compared the acute (96 h) lethal toxicity to six freshwater invertebrate species of NaHCO3 and two synthetic CBM waters, with ionic proportions representative of water from CBM wells across New South Wales (NSW) and Queensland (Qld), in Australia. The ranking of LC50 values expressed as total salinity was consistent with the hypotheses. However, when toxicity was expressed as bicarbonate concentration, the hypothesis that the toxicity of coal bed waters would be explained by bicarbonate concentration was not well supported, and other ionic components were either ameliorating or exacerbating the NaHCO3 toxicity. Our findings showed NaHCO3 was more toxic than NaCl and that the NaHCO3 proportion of synthetic CBM waters drives toxicity, however other ions are altering the toxicity of bicarbonate. [ABSTRACT FROM AUTHOR]