Development of a multi-objective reservoir operation model for water quality-quantity management.

This study aims to develop a multi-objective quantitative-qualitative reservoir operation model (MOQQROM) by a simulation-optimization approach. However, the main challenge of these models is their computational complexity. The simulation-optimization method used in this study consists of CE-QUAL-W2 as a hydrodynamic and water quality simulation model and a multi-objective firefly algorithm-k nearest neighbor (MOFA-KNN) as an optimization algorithm which is an efficient algorithm to overcome the computational burden in simulation-optimization approaches by decreasing simulation model calls. MOFA-KNN was expanded for this study, and its performance was evaluated in the MOQQROM. Three objectives were considered in this study, including (1) the sum of the squared mass of total dissolved solids (TDS), (2) the sum of the squared temperature difference between reservoir inflow and outflow as water quality objectives, and (3) the vulnerability index as a water quantity objective. Aidoghmoush reservoir was employed as a case study, and the model was investigated under three scenarios, including the normal, wet, and dry years. Results showed the expanded MOFA-KNN reduced the number of original simulation model calls compared to the total number of simulations in MOQQROM by more than 99%, indicating its efficacy in significantly reducing execution time. The three most desired operating policies for meeting each objective were selected for investigation. Results showed that the operation policy with the best value for the second objective could be chosen as a compromise policy to balance the two conflicting goals of improving quality and supplying the demand in normal and wet scenarios. In terms of contamination mass, this policy was, on average, 16% worse than the first policy and 40% better than the third policy in the normal scenario. In the wet scenario, it was, on average, 55% worse than the first policy and 16% better than the third policy. The outflow temperature of this policy was, on average, only 8.35% different from the inflow temperature in the normal scenario and 0.93% different in the wet scenario. The performance of the developed model is satisfactory.

Investigation on structure and photoluminescence properties of Ho3+ doped Ca3(VO4)2 phosphors for luminescent devices.

This study focuses on the synthesis and characterization of Ho3+ doped Ca3(VO4)2 phosphor for potential application in solid-state lighting technology. A citrate-based sol-gel process is optimized to achieve sheet-like morphologies in the phosphor material. The investigation reveals UV absorption at 371 nm, indicating a band gap of 3.28 eV. Emission transitions at (506, 541, and 651) nm are observed when excited at 451 nm, with an optimal Ho3+ concentration of 0.05 mol resulting in robust green emission at 541 nm. The concentration quenching in Ca3(VO4)2:xHo3+ phosphors is discussed in detail with Blesse's and Dexter's models. The concentration quenching effect found in the studied samples is due to the dipole-dipole interactions. Judd-Ofelt intensity parameters were calculated from the excitation bands, and for Ω 2, Ω 4, and Ω 6 are (0.16, 0.17, and 0.36) × 10-20 cm2, respectively. The emission properties for the (5S2 + 5F4) → 5I8 and 5F5 → 5I8 transitions are also estimated with J-O parameters. The higher magnitude of branching ratios (83%) and emission cross-sections (1.6 × 10-21 cm2) suggest that the Ca3(VO4)2:0.05Ho3+ phosphor materials may be suitable for efficient green-emitting device applications. The CIE coordinates confirm the potential of Ho3+-doped phosphors for green emissions, making them suitable for solid-state lighting and display technology.

Proteomic analysis of plasma at the preterminal stage of rhesus nonhuman primates exposed to a lethal total-body dose of gamma-radiation.

The identification and validation of radiation biomarkers is critical for assessing the radiation dose received in exposed individuals and for developing radiation medical countermeasures that can be used to treat acute radiation syndrome (ARS). Additionally, a fundamental understanding of the effects of radiation injury could further aid in the identification and development of therapeutic targets for mitigating radiation damage. In this study, blood samples were collected from fourteen male nonhuman primates (NHPs) that were exposed to 7.2 Gy ionizing radiation at various time points (seven days prior to irradiation; 1, 13, and 25 days post-irradiation; and immediately prior to the euthanasia of moribund (preterminal) animals). Plasma was isolated from these samples and was analyzed using a liquid chromatography tandem mass spectrometry approach in an effort to determine the effects of radiation on plasma proteomic profiles. The primary objective was to determine if the radiation-induced expression of specific proteins could serve as an early predictor for health decline leading to a preterminal phenotype. Our results suggest that radiation induced a complex temporal response in which some features exhibit upregulation while others trend downward. These statistically significantly altered features varied from pre-irradiation levels by as much as tenfold. Specifically, we found the expression of integrin alpha and thrombospondin correlated in peripheral blood with the preterminal stage. The differential expression of these proteins implicates dysregulation of biological processes such as hemostasis, inflammation, and immune response that could be leveraged for mitigating radiation-induced adverse effects.

Optimizing feature selection with gradient boosting machines in PLS regression for predicting moisture and protein in multi-country corn kernels via NIR spectroscopy.

Differences in moisture and protein content impact both nutritional value and processing efficiency of corn kernels. Near-infrared (NIR) spectroscopy can be used to estimate kernel composition, but models trained on a few environments may underestimate error rates and bias. We assembled corn samples from diverse international environments and used NIR with chemometrics and partial least squares regression (PLSR) to determine moisture and protein. The potential of five feature selection methods to improve prediction accuracy was assessed by extracting sensitive wavelengths. Gradient boosting machines (GBMs), particularly CatBoost and LightGBM, were found to effectively select crucial wavelengths for moisture (1409, 1900, 1908, 1932, 1953, 2174 nm) and protein (887, 1212, 1705, 1891, 2097, 2456 nm). SHAP plots highlighted significant wavelength contributions to model prediction. These results illustrate GBMs' effectiveness in feature engineering for agricultural and food sector applications, including developing multi-country global calibration models for moisture and protein in corn kernels.

Skeletal muscle mitochondrial dysfunction mediated by Pseudomonas aeruginosa quorum-sensing transcription factor MvfR: reversing effects with anti-MvfR and mitochondrial-targeted compounds.

Sepsis and chronic infections with Pseudomonas aeruginosa, a leading "ESKAPE" bacterial pathogen, are associated with increased morbidity and mortality and skeletal muscle atrophy. The actions of this pathogen on skeletal muscle remain poorly understood. In skeletal muscle, mitochondria serve as a crucial energy source, which may be perturbed by infection. Here, using the well-established backburn and infection model of murine P. aeruginosa infection, we deciphered the systemic impact of the quorum-sensing transcription factor MvfR (multiple virulence factor regulator) by interrogating, 5 days post-infection, its effect on mitochondrial-related functions in the gastrocnemius skeletal muscle and the outcome of the pharmacological inhibition of MvfR function and that of the mitochondrial-targeted peptide, Szeto-Schiller 31 (SS-31). Our findings show that the MvfR perturbs adenosine triphosphate generation, oxidative phosphorylation, and antioxidant response, elevates the production of reactive oxygen species, and promotes oxidative damage of mitochondrial DNA in the gastrocnemius muscle of infected mice. These impairments in mitochondrial-related functions were corroborated by the alteration of key mitochondrial proteins involved in electron transport, mitochondrial biogenesis, dynamics and quality control, and mitochondrial uncoupling. Pharmacological inhibition of MvfR using the potent anti-MvfR lead, D88, we developed, or the mitochondrial-targeted peptide SS-31 rescued the MvfR-mediated alterations observed in mice infected with the wild-type strain PA14. Our study provides insights into the actions of MvfR in orchestrating mitochondrial dysfunction in the skeletal murine muscle, and it presents novel therapeutic approaches for optimizing clinical outcomes in affected patients. IMPORTANCE: Skeletal muscle, pivotal for many functions in the human body, including breathing and protecting internal organs, contains abundant mitochondria essential for maintaining cellular homeostasis during infection. The effect of Pseudomonas aeruginosa (PA) infections on skeletal muscle remains poorly understood. Our study delves into the role of a central quorum-sensing transcription factor, multiple virulence factor regulator (MvfR), that controls the expression of multiple acute and chronic virulence functions that contribute to the pathogenicity of PA. The significance of our study lies in the role of MvfR in the metabolic perturbances linked to mitochondrial functions in skeletal muscle and the effectiveness of the novel MvfR inhibitor and the mitochondrial-targeted peptide SS-31 in alleviating the mitochondrial disturbances caused by PA in skeletal muscle. Inhibiting MvfR or interfering with its effects can be a potential therapeutic strategy to curb PA virulence.

Effect of Home-Based Pulmonary Rehabilitation on Pulmonary Fibrosis.

BACKGROUND: Pulmonary fibrosis is a chronic, progressive lung condition that involves lung tissue scarring and thickening. The effects of home-based pulmonary rehabilitation (PR) in post-covid pulmonary fibrosis (PCPF) and other forms of fibrosis together have not been evaluated. This study aims to evaluate the effectiveness of home-based pulmonary rehabilitation on pulmonary function, functional capacity, and health-related quality of life in people with pulmonary fibrosis (post-COVID pulmonary fibrosis, pulmonary fibrosis secondary to pulmonary tuberculosis (TB), pulmonary fibrosis secondary to interstitial lung disease (ILD), pulmonary fibrosis secondary to bronchiectasis). METHODS: A single-group pretest-posttest experimental study was performed after recruiting 98 pulmonary fibrosis subjects from K.M.C hospitals. After being screened for the inclusion and exclusion criteria, 45 subjects were analyzed, and 6 subjects were lost to follow-up.  A home-based pulmonary rehabilitation program was carried out for 8 weeks (warm-up, stretching exercises, aerobic exercise, strength training for upper limb and lower limb, breathing exercises mainly involved; others: energy saving techniques, controlled coughing techniques, dyspnea relieving positions). The program was supervised via weekly phone calls. Pulmonary function (Pulmonary function test), exercise capacity (6-minute walk test), dyspnea (modified Borg scale), and health-related quality of life (SF-36) were evaluated before and after the intervention. During the enrollment and after the 6-minute walk test, saturation of peripheral oxygen (SPO2) level was also evaluated pre-intervention and after the 8-weeks program. RESULTS: Pulmonary function [FVC(L) t = -12.52, p<0.05; FEV1(L) t = -2.56, p<0.05; FEV1/FVC t = 7.98, p<0.05 and DLCO (ml/min/mmHg) t = -5.13, p<0.05], 6MWD [MD 88.66; p<0.05] and HRQOL measured by SF-36 scores (p<0.05) were improved significantly. Both the baseline SPO2 level before the 6MWT [MD 1.07, p<0.05] and the SPO2 level after the 6MWT [MD 1.16, p<0.05] showed a significant improvement. The rating of perceived exertion(dyspnea) [MD 1.30, p<0.05] was reduced significantly after the 8-week program. CONCLUSION: Our study shows that home-based pulmonary rehabilitation is an effective option for improving lung function and physical functional capacity by reducing dyspnea perception and improving the saturation of peripheral oxygen (SPO2) level, and enhancing the quality of life in people with pulmonary fibrosis.

Pathology of acute sub-lethal or near-lethal irradiation of nonhuman primates prophylaxed with the nutraceutical, gamma tocotrienol.

Exposure to high, marginally lethal doses or higher of ionizing radiation, either intentional or accidental, results in injury to various organs. Currently, there is only a limited number of safe and effective radiation countermeasures approved by US Food and Drug Administration for such injuries. These approved agents are effective for only the hematopoietic component of the acute radiation syndrome and must be administered only after the exposure event: currently, there is no FDA-approved agent that can be used prophylactically. The nutraceutical, gamma-tocotrienol (GT3) has been found to be a promising radioprotector of such exposure-related injuries, especially those of a hematopoietic nature, when tested in either rodents or nonhuman primates. We investigated the nature of injuries and the possible protective effects of GT3 within select organ systems/tissues caused by both non-lethal level (4.0 Gy), as well as potentially lethal level (5.8 Gy) of ionizing radiation, delivered as total-body or partial-body exposure. Results indicated that the most severe, dose-dependent injuries occurred within those organ systems with strong self-renewing capacities (e.g., the lymphohematopoietic and gastrointestinal systems), while in other tissues (e.g., liver, kidney, lung) endowed with less self-renewal, the pathologies noted tended to be less pronounced and less dependent on the level of exposure dose or on the applied exposure regimen. The prophylactic use of the test nutraceutical, GT3, appeared to limit the extent of irradiation-associated pathology within blood forming tissues and, to some extent, within the small intestine of the gastrointestinal tract. No distinct, global pattern of bodily protection was noted with the agent's use, although a hint of a possible radioprotective benefit was suggested not only by a lessening of apparent injury within select organ systems, but also by way of noting the lack of early onset of moribundity within select GT3-treated animals.

Human Monkeypox Virus and Host Immunity: New Challenges in Diagnostics and Treatment Strategies.

The monkeypox virus (MPXV), responsible for human disease, has historically been limited to the African countries, with only a few isolated instances reported elsewhere in the world. Nevertheless, in recent years, there have been occurrences of monkeypox in regions where the disease is typically absent, which has garnered global interest. Within a period of less than four months, the incidence of MPXV infections has surged to over 48,000 cases, resulting in a total of 13 deaths. This chapter has addressed the genetics of the pox virus, specifically the human monkeypox virus, and its interaction with the immune systems of host organisms. The present chapter is skillfully constructed, encompassing diagnostic methodologies that span from traditional to developing molecular techniques. Furthermore, the chapter provides a succinct analysis of the therapeutic methods employed, potential future developments, and the various emerging difficulties encountered in illness management.

Silicon regulates phosphate deficiency through involvement of auxin and nitric oxide in barley roots.

MAIN CONCLUSION: Silicon application mitigates phosphate deficiency in barley through an interplay with auxin and nitric oxide, enhancing growth, photosynthesis, and redox balance, highlighting the potential of silicon as a fertilizer for overcoming nutritional stresses. Silicon (Si) is reported to attenuate nutritional stresses in plants, but studies on the effect of Si application to plants grown under phosphate (Pi) deficiency are still very scarce, especially in barley. Therefore, the present work was undertaken to investigate the potential role of Si in mitigating the adverse impacts of Pi deficiency in barley Hordeum vulgare L. (var. BH902). Further, the involvement of two key regulatory signaling molecules--auxin and nitric oxide (NO)--in Si-induced tolerance against Pi deficiency in barley was tested. Morphological attributes, photosynthetic parameters, oxidative stress markers (O2·-, H2O2, and MDA), antioxidant system (enzymatic--APX, CAT, SOD, GR, DHAR, MDHAR as well as non-enzymatic--AsA and GSH), NO content, and proline metabolism were the key traits that were assessed under different treatments. The P deficiency distinctly declined growth of barley seedlings, which was due to enhancement in oxidative stress leading to inhibition of photosynthesis. These results were also in parallel with an enhancement in antioxidant activity, particularly SOD and CAT, and endogenous proline level and its biosynthetic enzyme (P5CS). The addition of Si exhibited beneficial effects on barley plants grown in Pi-deficient medium as reflected in increased growth, photosynthetic activity, and redox balance through the regulation of antioxidant machinery particularly ascorbate-glutathione cycle. We noticed that auxin and NO were also found to be independently participating in Si-mediated improvement of growth and other parameters in barley roots under Pi deficiency. Data of gene expression analysis for PHOSPHATE TRANSPORTER1 (HvPHT1) indicate that Si helps in increasing Pi uptake as per the need of Pi-deficient barley seedlings, and also auxin and NO both appear to help Si in accomplishing this task probably by inducing lateral root formation. These results are suggestive of possible application of Si as a fertilizer to correct the negative effects of nutritional stresses in plants. Further research at genetic level to understand Si-induced mechanisms for mitigating Pi deficiency can be helpful in the development of new varieties with improved tolerance against Pi deficiency, especially for cultivation in areas with Pi-deficient soils.

Knowledge, Attitude, and Practice of Physiotherapists about Cardiac Rehabilitation Program Adherence among Patients Discharged from the Hospital after Cardiac Surgery in India.

Background: In most settings, patients receive phase 1 cardiac rehabilitation in CTVS ICU at the hospital, but there are several barriers to follow-up after patients are discharged from the hospital. Physiotherapists play an important role in the enrolment and continuation of cardiac rehabilitation. Thus, we aim to study the knowledge, attitude, and practice of physiotherapists about CR program adherence among patients discharged from the hospital after cardiac surgery. Objectives: (i) To study the knowledge of physiotherapists about the importance of cardiac rehabilitation after discharge; (ii) to know the attitude of physiotherapists towards cardiac surgery patients after discharge; and (iii) to know what approach various centres are applying for patients after discharge to ensure adherence to cardiac rehabilitation. Methods: A questionnaire was developed with reference to the objectives of the study, which was answered by a total of 127 physiotherapists. Results: The overall response rate was 42.3%; nearly 35.4% of the participants indicated that they knew a lot about CR, while 5.5% said they knew very little. Regarding the program's content, 36.2% of participants reported having a medium degree of awareness of the diverse CR components, while 8.6% reported having very little knowledge of them. Only about one-third, 35.7% stated that CR in India is effective and 95% believed that CR will have an added value for the country. Approximately 80% of respondents thought that it would be challenging for a physiotherapist to recommend patients to a CR in the nation. Nearly 35% of respondents believed that they, "themselves as physios," needed to commence CR, and slightly less than 70% thought that doctors were required to choose and refer the patients when asked who should take the initiative to start this kind of programme in the country. A little over 40% of respondents said that insurance firms are also involved in starting a CR programme. Conclusion: Physiotherapists have good knowledge of cardiac rehabilitation. However, their attitude and practice towards adherence to exercise protocols are confounded by various clinician- and patient-level factors.

Does Elevated Mean-Arterial Pressure Lead to Better Outcomes in Degenerative Cervical Myelopathy?- A Prospective, Pilot Randomized Control Trial.

STUDY DESIGN: Randomized Control Trial. OBJECTIVE: DCM refers to compression of spinal cord either due to static/dynamic causes or commonly, a result of combination of both. Number of variables exist, which determine prognosis post-surgery. Role of intra-operative blood pressure has not been analyzed in depth in current literature. Elevating MAP post SCI is widely practiced and forms a recommendation of AANS/CNS Joint Committee Guidelines. This led us to investigate role played by elevated MAP during surgery for DCM, in order to optimize outcomes. METHODS: This prospective randomized comparative pilot study was conducted at a tertiary care spine centre. 84 patients were randomly divided in two groups. Group 1 had intra-operative MAP in normal range. Group 2, had intra-operative BP 20 mmHg higher than preoperative average MAP with a variation of + 5 mmHg. Outcomes were recorded at 3 months, 6 months and 1 year by mJOA, VAS and ASIA scale. RESULTS: Neurological improvement was documented in 19/30 (63.3%) patients of hypertensive group compared to 16/30 (53.3%) patients of normotensive group. Improvements in mJOA scores were better for hypertensive group during the 1-year follow-up. Improvement in VAS scores were comparable between two groups, but at 1-year follow-up the VAS score of hypertensive groups was significantly lower. CONCLUSION: MAP should be individualized according to preoperative average blood pressure assessment of patient. Keeping intraoperative MAP at higher level (preoperative MAP + 20 mmHg) during surgery for DCM can result in better outcomes.

A comparative survey between cascade correlation neural network (CCNN) and feedforward neural network (FFNN) machine learning models for forecasting suspended sediment concentration.

Suspended sediment concentration prediction is critical for the design of reservoirs, dams, rivers ecosystems, various operations of aquatic resource structure, environmental safety, and water management. In this study, two different machine models, namely the cascade correlation neural network (CCNN) and feedforward neural network (FFNN) were applied to predict daily-suspended sediment concentration (SSC) at Simga and Jondhara stations in Sheonath basin, India. Daily-suspended sediment concentration and discharge data from 2010 to 2015 were collected and used to develop the model to predict suspended sediment concentration. The developed models were evaluated using statistical indices like Nash and Sutcliffe efficiency coefficient (NES), root mean square error (RMSE), Willmott's index of agreement (WI), and Legates-McCabe's index (LM), supplemented by a scatter plot, density plots, histograms and Taylor diagram for graphical representation. The developed model was evaluated and compared with CCNN and FFNN. Nine input combinations were explored using different lag-times for discharge (Qt-n) and suspended sediment concentration (St-n) as input variables, with the current suspended sediment concentration as the desired output, to develop CCNN and FFNN models. The CCNN4 model with 4 lagged inputs (St-1, St-2, St-3, St-4) outperformed the other developed models with the lowest RMSE = 95.02 mg/l and the highest NES = 0.0.662, WI = 0.890 and LM = 0.668 for the Jondhara Station while the same CCNN4 model secure as the best with the lowest RMSE = 53.71 mg/l and the highest NES = 0.785, WI = 0.936 and LM = 0.788 for the Simga Station. The result shows the CCNN model was better than the FFNN model for predicting daily-suspended sediment at both stations in the Sheonath basin, India. Overall, CCNN showed better forecasting potential for suspended sediment concentration compared to FFNN at both stations, demonstrating their applicability for hydrological forecasting with complex relationships.

Mycoplasma pneumoniae Outbreak in 2023: Post-pandemic Resurgence of an Atypical Bacterial Pathogen.

The syndromic nature of infections caused by pneumonia-causing pathogens including Mycoplasma pneumoniae necessitates detection via multiplex PCR for accurate and timely diagnosis to control the infection spread. In this study, we demonstrate an increase in the detection of M. pneumoniae in the outpatient population, during 2023, as compared to the previous two years (2021-2022). In this aggregated survey, respiratory samples collected within the continental United States were tested for the presence of M. pneumoniae and other respiratory bacterial and viral pathogens using a multiplex PCR assay. Patient data was analyzed on the basis of age, gender and geographical location. The positive detection of M. pneumoniae in 2021 and 2022 was 0.004% and 0.006%, respectively. The positivity rate of M. pneumoniae in 2023 increased to 0.21%. The highest proportion of M. pneumoniae cases were detected from Georgia with the outbreak generally concentrated in large urban settings. Median age of the patients testing positive for M. pneumoniae was 10 (interquartile range [IQR] 8-18) years with an almost equal distribution between male and female patients. Other respiratory, viral and bacterial, pathogens detected in samples positive for M. pneumoniae were similar in proportion to the M. pneumonia-negative population. A survey of the ICD-10 codes submitted in conjunction with the samples suggests that the current outbreak is mostly associated with upper respiratory tract infections. The present study is the first detailed report in the United States that shows an unprecedented increase in the detection of M. pneumoniae in the outpatient population during 2023. Our analysis suggests that this outbreak was not associated with any other bacterial or viral respiratory pathogen. The outbreak of this atypical pathogen was concentrated in the pediatric population in large urban areas. The 2023 outbreak could be a return of the cyclical M. pneumoniae outbreaks witnessed prior to the COVID-19 pandemic. Our study highlights the importance of performing continuous surveillance of respiratory pathogens, especially in the altered epidemiological landscape of the post-COVID world.

Skeletal Muscle Mitochondrial Dysfunction Mediated by Pseudomonas aeruginosa Quorum Sensing Transcription Factor MvfR: Reversing Effects with Anti-MvfR and Mitochondrial-Targeted Compounds.

Sepsis and chronic infections with Pseudomonas aeruginosa, a leading "ESKAPE" bacterial pathogen, are associated with increased morbidity and mortality and skeletal muscle atrophy. The actions of this pathogen on skeletal muscle remain poorly understood. In skeletal muscle, mitochondria serve as a crucial energy source, which may be perturbed by infection. Here, using the well-established backburn and infection model of murine P. aeruginosa infection, we deciphered the systemic impact of the quorum sensing (QS) transcription factor MvfR by interrogating five days post-infection its effect on mitochondrial-related functions in the gastrocnemius skeletal muscle and the outcome of the pharmacological inhibition of MvfR function and that of the mitochondrial-targeted peptide, Szeto-Schiller 31 (SS-31). Our findings show that the MvfR perturbs ATP generation, oxidative phosphorylation (OXPHOS), and antioxidant response, elevates the production of reactive oxygen species, and promotes oxidative damage of mitochondrial DNA in the gastrocnemius muscle of infected mice. These impairments in mitochondrial-related functions were corroborated by the alteration of key mitochondrial proteins involved in electron transport, mitochondrial biogenesis, dynamics and quality control, and mitochondrial uncoupling. Pharmacological inhibition of MvfR using the potent anti-MvfR lead, D88, we developed, or the mitochondrial-targeted peptide SS-31 rescued the MvfR- mediated alterations observed in mice infected with the wild-type strain PA14. Our study provides insights into the actions of MvfR in orchestrating mitochondrial dysfunction in the skeletal murine muscle, and it presents novel therapeutic approaches for optimizing clinical outcomes in affected patients.

Pharmacokinetic and Metabolomic Studies with a Promising Radiation Countermeasure, BBT-059 (PEGylated interleukin-11), in Rhesus Nonhuman Primates.

BBT-059, a long-acting PEGylated interleukin-11 (IL-11) analog that is believed to have hematopoietic promoting and anti-apoptotic properties, is being developed as a potential radiation medical countermeasure (MCM) for hematopoietic acute radiation syndrome (H-ARS). This agent has been shown to improve survival in lethally irradiated mice. To further evaluate the drug's toxicity and safety profile, 12 naïve nonhuman primates (NHPs, rhesus macaques) were administered one of three doses of BBT-059 subcutaneously and were monitored for the next 21 days. Blood samples were collected throughout the study to assess the pharmacokinetics (PK) and pharmacodynamics (PD) of the drug as well as its effects on complete blood counts, cytokines, vital signs, and to conduct metabolomic studies. No adverse effects were detected in any treatment group during the study. Short-term changes in metabolomic profiles were present in all groups treated with BBT-059 beginning immediately after drug administration and reverting to near normal levels by the end of the study period. Several pathways and metabolites, particularly those related to inflammation and steroid hormone biosynthesis, were activated by BBT-059 administration. Taken together, these observations suggest that BBT-059 has a good safety profile for further development as a radiation MCM for regulatory approval for human use.

Discriminatory performance of the pulpal inflammatory biomarkers; Interleukin-8 and TNF-α in patients with symptoms indicative of reversible and irreversible pulpitis: A diagnostic accuracy study.

AIM: The success of vital pulp treatment (VPT) procedures is dependent on an accurate diagnosis of the pulpal inflammatory condition. Compared with current subjective pulpal diagnostic tests, inflammatory molecular biomarkers involved in the pathogenesis of pulpitis represent potential objective indicators of the degree of pulpal inflammation. Therefore, the aim of this study was to quantify level of inflammatory biomarkers - Interleukin 8 (IL-8) and TNF-α in patients diagnosed with reversible pulpitis (RP), irreversible pulpitis (IR) and normal pulp (NP) and investigate their diagnostic accuracy in differentiating between healthy and inflamed conditions. METHODOLOGY: This prospective, cross-sectional study enrolled 72 patients aged 14-53 years with extremely deep carious lesions after establishing a clinical diagnosis of RP (n = 42), symptomatic IR (n = 22) and NP (n = 8). 50 µL of pulpal blood sample was collected from all the patients using a micropipette after pulpal exposure. The level of IL-8 and TNF-α was assessed in pg/mL using enzyme-linked immunosorbent assays. Mann-Whitney U test was applied to establish the association between IL-8/TNF-α level and degree of pulp inflammation. Receiver operating curve (ROC) analysis was carried out to calculate area under the curve (AUC) for RP versus IR. Cut-off values were established using Youden's index. RESULTS: IL-8 and TNF-α levels differed significantly between RP and IR groups (p ≤ .001). The median value of IL-8 in RP and IP groups was 259.8 pg/mL [187.5-310.0] and 1357.8 pg/mL [1036.7-2177.6] respectively. The AUC-ROC curve for RP versus IR was 0.997 with 95.5% sensitivity and 99.76% specificity. The median value of TNF-α in RP and IR groups was 75.4 pg/mL [62.7-95.8] and 157.6 pg/mL [94.1-347.3]. The AUC-ROC curve for TNF-α was 0.812 with a sensitivity and specificity of 59.1% and 92.1%, respectively. IL-8 and TNF-α levels were below detection levels for all NP samples. CONCLUSION: This study showed that pulpal blood could provide an excellent medium for establishing pulpal diagnosis under extremely deep carious lesions. The selected cytokines, IL-8 and TNF-α, demonstrated excellent discriminatory performance for reversible and irreversible pulpitis. Future studies should correlate the IL-8/TNF-α levels with VPT treatment outcomes.

Buprenorphine affects the initiation and severity of interleukin-induced acute pancreatitis in mice.

Acute pancreatitis (AP) is a common disease with no targeted therapy and has varied outcomes ranging from spontaneous resolution to being lethal. Although typically painful, AP can also be painless. Various agents, including opioids, are used for pain control in AP; the risks and benefits of which are often debated. As experimental AP in mice is used to study the efficacy of potential therapies, we studied the effect of a commonly used opioid, buprenorphine, on the initiation and progression of AP. For this, we administered extended-release buprenorphine subcutaneously before inducing the previously established severe AP model that uses interleukins 12 and 18 (IL12,18) in genetically obese (ob/ob) mice and compared this to mice with AP but without the drug. Mice were monitored over 3 days, and parameters of AP induction and progression were compared. Buprenorphine significantly reduced serum amylase, lipase, pancreatic necrosis, and AP-associated fat necrosis, which is ubiquitous in obese mice and humans. Buprenorphine delayed the AP-associated reduction of carotid artery pulse distention and the development of hypothermia, hastened renal injury, and muted the early increase in respiratory rate versus IL12,18 alone. The site of buprenorphine injection appeared erythematous, inflamed, and microscopically showed thinning, loss of epidermal layers that had increased apoptosis. In summary, subcutaneous extended-release buprenorphine interfered with the induction of AP by reducing serum amylase, lipase, pancreatic and fat necrosis, the worsening of AP by delaying hypotension, hypothermia, while hastening renal injury, respiratory depression, and causing cutaneous injury at the site of injection.NEW & NOTEWORTHY Extended-release buprenorphine interferes with the initiation and progression of acute pancreatitis at multiple levels.

Redox regulation by priming agents towards a sustainable agriculture.

Plant are sessile organisms that are often subjected to a multitude of environmental stresses, with the occurrence of these events being further intensified by global climate change. Crop species therefore require specific adaptations to tolerate climatic variability for sustainable food production. Plant stress results in excess accumulation of reactive oxygen species (ROS) leading to oxidative stress, and loss of cellular redox balance in the plant cells. Moreover, enhancement of cellular oxidation as well as oxidative signals have recently been recognized as crucial players in plant growth regulation under stress conditions. Multiple roles of redox regulation in crop production have been well documented, and major emphasis has focused on key redox-regulated proteins and non-protein molecules, such as NAD(P)H, thioredoxins, glutathione, glutaredoxins, peroxiredoxins, ascorbate, and reduced ferredoxin. These have been widely implicated in the regulation of (epi)genetic factors modulating growth and vigor of crop plants, particularly within an agricultural context. In this regard, priming with the employment of chemical and biological agents has emerged as a fascinating approach to improve plant tolerance against various abiotic and biotic stressors. Priming in plants is a physiological process, where prior exposure to specific stressors induces a state of heightened alertness, enabling a more rapid and effective defense response upon subsequent encounters with similar challenges. Priming is reported to play an important role in the regulation of cellular redox homeostasis, maximizing crop productivity under stress conditions and thus achieving yield security. By taking this into consideration, the present review is an up-to-date critical evaluation of promising plant priming technologies and their role in the regulation of redox components towards enhanced plant adaptations to extreme unfavorable environmental conditions. The challenges and opportunities of plant priming are addressed, with the aim to encourage future research in this field towards effective application in crop stress management including horticultural species.

Neutrophil-driven and interleukin-36γ-associated ocular surface inflammation in chronic Stevens-Johnson syndrome.

PURPOSE: This study aims to elucidate the tear proteome and understand the underlying molecular mechanisms involved in the ocular complications following Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). METHODS: Mass spectrometry (MS) was performed to quantify the tear fluid proteins from chronic SJS/TEN patients (n = 22 eyes) and age- and gender-matched controls (n = 22 eyes). The candidate proteins were validated using ELISA (n = 80 eyes) in tear samples and immunohistochemistry (IHC; n = 12) in eyelid margin specimens. These proteins were compared for significant differences based on age, gender, disease duration, and ocular severity. RESULTS: A total of 1692 tear fluid proteins were identified, of which 470 were significantly differentially regulated in chronic SJS/TEN. The top 10 significantly upregulated proteins were neutrophil secretions including neutrophil elastase (p < .0001), defensin (p < .0001), and matrix metalloproteinase 8 (p < .0001). The presence of neutrophils was confirmed by the upregulation of IL-8 (p < .001) in tears, a key cytokine known for recruiting neutrophils. Additionally, positive expression of myeloperoxidase was observed in the keratinized eyelid margins of SJS/TEN to validate the presence of neutrophils. Among 41 unique proteins identified by MS, IL-36γ (p < .01) was expressed in three SJS/TEN patients and was confirmed in SJS/TEN tears and eyelid margins by ELISA and IHC, respectively. IL-36γ was specifically expressed in the superficial layers of eyelid margin keratinized conjunctiva. The majority of the significantly downregulated proteins were lacrimal gland secretions such as lacritin (p < .0001) and opiorphin (p < .002). Neutrophil elastase (p < .02) was significantly elevated in patients with severe eyelid margin keratinization. CONCLUSION: Our observations indicate a clear correlation between eyelid margin keratinization and the expression of IL-36γ, potentially mediated by neutrophils recruited via IL-8. Future experimental studies are needed to test the role of therapies targeting IL-8 and/or IL-36γ in reducing eyelid margin keratinization and its associated ocular complications in SJS/TEN.