Implementation of a Novel Prehospital Clinical Decision Tool and ECG Transmission for STEMI Significantly Reduces Door-to-Balloon Time and Sex-Based Disparities.

Background: An important method employed to reduce door to balloon time (DTBT) for ST segment elevation Myocardial Infarctions (STEMIs) is a prehospital MI alert. The purpose of this retrospective study was to examine the effects of an educational intervention using a novel decision support method of STEMI notification and prehospital electrocardiogram (ECG) transmission on DTBT.Methods: An ongoing database (4/4/2000 - present) is maintained to track STEMI alerts. In 2007, an MI alert program began; emergency medicine physicians could activate a "prehospital MI alert". In October 2015, modems were purchased for Emergency Medical Services personnel to transmit ECGs. There was concurrent implementation of a decision support tool for identifying STEMI. Sex was assigned as indicated in the medical record. Data were analyzed in two groups: Pre-2016 (PRE) and 2016-2022 (POST).Results: In total, 3,153 patients (1,301 PRE; 1,852 POST) were assessed; the average age was 65.2 years, 32.6% female, 87.7% white with significant differences in age and race between the two cohorts. Of the total 3,153 MI alerts, 239 were false activations, leaving 2,914 for analysis. 2,115 (72.6%) had cardiac catheterization while 16 (6.7%) of the 239 had a cardiac catheterization. There was an overall decrease in DTBT of 27.5% PRE to POST of prehospital ECG transmission (p <0.001); PRE median time was 74.5 minutes vs. 55 minutes POST. There was no significant difference between rates of cardiac catheterization PRE and POST for all patients. After accounting for age, race, and mode of arrival, DTBT was 12.2% longer in women, as compared to men (p < 0.001) PRE vs. POST. DTBT among women was significantly shorter when comparing PRE to POST periods (median 77 minutes vs. 60 minutes; p = 0.0001). There was no significant sex difference in the proportion of those with cardiac catheterization between the two cohorts (62.5% vs. 63.5%; p = 0.73).Conclusion: Introduction of a decision support tool with prehospital ECG transmission with prehospital ECG transmission decreased overall DTBT by 20 minutes (27.5%). Women in the study had a 17-minute decrease in DTBT (22%), but their DTBT remained 12.2% longer than men for reasons that remain unclear.

Impact of Preoperative Serum Albumin Level on the Outcome of Colorectal Cancer Surgery.

Background Gastrointestinal malignancy surgeries are known to have a risk of postoperative complications. Preoperative nutritional status has been suggested as a potential predictor of postoperative outcomes, with low serum albumin levels utilized as a marker of malnutrition and increased risk of postoperative complications. This paper investigated the association between preoperative serum albumin levels and postoperative outcomes in patients undergoing colorectal cancer surgery. Methods This retrospective data-maintained study was based on all patients aged 18 years and above who underwent colorectal cancer surgery at King Abdulaziz Medical City, Riyadh, Saudi Arabia between 2015 and 2022. Results A total of 400 patients were included in the study. With an average age of 64.43 years. Males represented 254 (63%) of the patients, while females accounted for 146 (37%). Thirty percent of patients had hypoalbuminemia (i.e., albumin level below 35 g/L) before surgery. Among the sample, 112 (28%) experienced complications after surgery. The mean albumin level for patients who experienced postoperative complications was 30.46 g/L while patients without complications had a normal albumin level. As for the length of hospital stay, it was eight days for patients with a normal albumin level and 23 days for hypoalbuminemia patients. Conclusion In conclusion, preoperative hypoalbuminemia is associated with poor patient outcomes and can be utilized as a prognostic marker for patients in need of colorectal cancer surgery.

Structural insights into novel therapeutic deep eutectic systems with capric acid using 1D, 2D NMR and DSC techniques with superior gut permeability.

Therapeutic deep eutectic solvents (THEDSs) are the best exemplification of green alternative formulations of active pharmaceutical ingredients (APIs) that offer superlative properties of APIs. Previously, THEDESs of risperidone, fentanyl and levofloxacin with capric acid (CA) were developed by our group. These APIs share cyclic tertiary amine nuclei. Herein, DESs of two drugs bearing cyclic tertiary amine nucleus, namely, droperidol and aripiprazole, in the presence of CA, were investigated as model drugs. Comprehensive analyses were conducted using liquid-state 1D and 2D NMR and differential scanning calorimetry (DSC) to elucidate the regiochemistry and thermodynamic mechanisms bringing about those THEDESs. Everted gut sac technique was used to study the flux of the developed THEDESs. 1D and 2D NMR techniques analyses revealed the importance of cyclic tertiary amine nuclei in forming interactions with CA. This was confirmed by the downfield shift of the protons proximal to the tertiary amine groups compared to the individual drugs. Diffusion NMR analysis (DOSY) showed a significant reduction in the diffusion coefficient of CA in the mixed system compared with CA in isolation. Thermal analysis of the two drugs revealed that the drugs have a low tendency to recrystallise upon melting but rather vitrify from a melt to form an amorphous solid. Interestingly, the superior absorption and flux of the THEDES formulation of droperidol was demonstrated using the ERIS. Collectively, this work provides a green method to attain liquid formulations of APIs with enhanced pharmacokinetic features.

Early Experience with a Novel Treatment for Menière's Disease: A Long Acting Dexamethasone Formulation for Precise Delivery to the Round Window Membrane.

OBJECTIVE: To investigate the safety and feasibility of precise delivery of a long-acting gel formulation containing 6% dexamethasone (SPT-2101) to the round window membrane for the treatment of Menière's disease. STUDY DESIGN: Prospective, unblinded, cohort study. SETTING: Tertiary care neurotology clinic. PATIENTS: Adults 18 to 85 years with a diagnosis of unilateral definite Menière's disease per Barany society criteria. INTERVENTIONS: A single injection of a long-acting gel formulation under direct visualization into the round window niche. MAIN OUTCOME MEASURES: Procedure success rate, adverse events, and vertigo control. Vertigo control was measured with definitive vertigo days (DVDs), defined as any day with a vertigo attack lasting 20 minutes or longer. RESULTS: Ten subjects with unilateral Menière's disease were enrolled. Precise placement of SPT-2101 at the round window was achieved in all subjects with in-office microendoscopy. Adverse events included one tympanic membrane perforation, which healed spontaneously after the study, and two instances of otitis media, which resolved with antibiotics. The average number of DVDs was 7.6 during the baseline month, decreasing to 3.3 by month 1, 3.7 by month 2, and 1.9 by month 3. Seventy percent of subjects had zero DVDs during the third month after treatment. CONCLUSIONS: SPT-2101 delivery to the round window is safe and feasible, and controlled trials are warranted to formally assess efficacy.

Biological invasions are a population-level rather than a species-level phenomenon.

Biological invasions pose a rapidly expanding threat to the persistence, functioning and service provisioning of ecosystems globally, and to socio-economic interests. The stages of successful invasions are driven by the same mechanism that underlies adaptive changes across species in general-via natural selection on intraspecific variation in traits that influence survival and reproductive performance (i.e., fitness). Surprisingly, however, the rapid progress in the field of invasion science has resulted in a predominance of species-level approaches (such as deny lists), often irrespective of natural selection theory, local adaptation and other population-level processes that govern successful invasions. To address these issues, we analyse non-native species dynamics at the population level by employing a database of European freshwater macroinvertebrate time series, to investigate spreading speed, abundance dynamics and impact assessments among populations. Our findings reveal substantial variability in spreading speed and abundance trends within and between macroinvertebrate species across biogeographic regions, indicating that levels of invasiveness and impact differ markedly. Discrepancies and inconsistencies among species-level risk screenings and real population-level data were also identified, highlighting the inherent challenges in accurately assessing population-level effects through species-level assessments. In recognition of the importance of population-level assessments, we urge a shift in invasive species management frameworks, which should account for the dynamics of different populations and their environmental context. Adopting an adaptive, region-specific and population-focused approach is imperative, considering the diverse ecological contexts and varying degrees of susceptibility. Such an approach could improve and refine risk assessments while promoting mechanistic understandings of risks and impacts, thereby enabling the development of more effective conservation and management strategies.

A novel biosensing strategy for identification of three important bacteria causing meningitis.

Bacterial meningitis is an acute infection which requires rapid diagnosis and treatment due to the high mortality and serious consequences of the disease. The purpose of this study was to design a homemade multiplex PCR and a novel fluorescence biosensor on chip (FBC) to detect three important agents of meningitis including Streptococcus pneumoniae (S. pneumoniae), Neisseria meningitidis (N. meningitidis), and Haemophilus influenzae (H. influenzae). The homemade multiplex PCR can diagnose three bacterial species simultaneously. Fabrication of FBC was carried out based on the deposition of lead nanoparticles on a quartz slide using the thermal evaporation method. Then, the SH-Cap Probe/Target ssDNA /FAM-Rep probe was loaded on lead film. The evaluation of the fluorescence reaction when the probes bind to the target ssDNA was assessed by a Cytation 5 Cell Imaging Multimode Reader Bio-Tek. The limit of detections (LOD) in homemade PCR and FBC to identify S. pneumoniae were 119 × 102 CFU/mL (0.27 ng/µL) and 380 CFU/mL (9 pg/µL), respectively. The LODs of homemade PCR and FBC for detection of N. meningitidis were 4.49 CFU/mL (1.1 pg/µL) and 13 × 103 CFU/mL (30 pg/µL), respectively. Our results confirmed the LODs of homemade PCR and FBC in detection of H. influenzae were 15.1 CFU/mL (30 fg/µL) and 41 × 102 CFU/mL (90 pg/ µL), respectively. Both techniques had appropriate sensitivity and specificity in detection of S. pneumoniae, N. meningitidis and H. influenzae.

Immunotherapy of Hematological Malignancies of Human B-Cell Origin with CD19 CAR T Lymphocytes.

Acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL) are hematological malignancies with high incidence rates that respond relatively well to conventional therapies. However, a major issue is the clinical emergence of patients with relapsed or refractory (r/r) NHL or ALL. In such circumstances, opportunities for complete remission significantly decline and mortality rates increase. The recent FDA approval of multiple cell-based therapies, Kymriah (tisagenlecleucel), Yescarta (axicabtagene ciloleucel), Tecartus (Brexucabtagene autoleucel KTE-X19), and Breyanzi (Lisocabtagene Maraleucel), has provided hope for those with r/r NHL and ALL. These new cell-based immunotherapies use genetically engineered chimeric antigen receptor (CAR) T-cells, whose success can be attributed to CAR's high specificity in recognizing B-cell-specific CD19 surface markers present on various B-cell malignancies and the subsequent initiation of anti-tumor activity. The efficacy of these treatments has led to promising results in many clinical trials, but relapses and adverse reactions such as cytokine release syndrome (CRS) and neurotoxicity (NT) remain pervasive, leaving areas for improvement in current and subsequent trials. In this review, we highlight the current information on traditional treatments of NHL and ALL, the design and manufacturing of various generations of CAR T-cells, the FDA approval of Kymriah, Yescarta Tecartus, and Breyanzi, and a summary of prominent clinical trials and the notable disadvantages of treatments. We further discuss approaches to potentially enhance CAR T-cell therapy for these malignancies, such as the inclusion of a suicide gene and use of FDA-approved drugs.

Neurosurgical neuromodulation therapy for psychiatric disorders.

Psychiatric disorders are among the leading contributors to global disease burden and disability. A significant portion of patients with psychiatric disorders remain treatment-refractory to best available therapy. With insights from the neurocircuitry of psychiatric disorders and extensive experience of neuromodulation with deep brain stimulation (DBS) in movement disorders, DBS is increasingly being considered to modulate the neural network in psychiatric disorders. Currently, obsessive-compulsive disorder (OCD) is the only U.S. FDA (United States Food and Drug Administration) approved DBS indication for psychiatric disorders. Medically refractory depression, addiction, and other psychiatric disorders are being explored for DBS neuromodulation. Studies evaluating DBS for psychiatric disorders are promising but lack larger, controlled studies. This paper presents a brief review and the current state of DBS and other neurosurgical neuromodulation therapies for OCD and other psychiatric disorders. We also present a brief review of MR-guided Focused Ultrasound (MRgFUS), a novel form of neurosurgical neuromodulation, which can target deep subcortical structures similar to DBS, but in a noninvasive fashion. Early experiences of neurosurgical neuromodulation therapies, including MRgFUS neuromodulation are encouraging in psychiatric disorders; however, they remain investigational. Currently, DBS and VNS are the only FDA approved neurosurgical neuromodulation options in properly selected cases of OCD and depression, respectively.

Antimicrobial stewardship knowledge, attitudes, and practices (KAP) among nurses.

We performed a knowledge, attitudes, and practice (KAP) survey of bedside nurses to evaluate perceptions of antimicrobial use and aid in the design of nursing-based antimicrobial stewardship interventions. The survey highlighted discrepancies in knowledge and practice as well as opportunities to improve communication with nursing colleagues.

Bridging the Gap: The Vital Role of Nursing in Caring for Military Members and Veterans and Their Families.

In 2011, a national call from The White House set in motion an initiative for action called Joining Forces to serve America's military families. This initiative, led by then-First Lady Michelle Obama and Dr. Jill Biden, was intended to unite public and private sectors to ensure active military service members, veterans, and their families had the educational, employment, and wellness resources they needed to succeed. Although the nursing profession started to respond to this call to action, it was never embraced as a priority. With nearly three million active-duty personnel, nearly one million reservists, more than 18 million veterans, and millions more families of our military and veteran community, it is time for the largest health care workforce to lead the care and wellness of our military and veteran community. [J Contin Educ Nurs. 2024;55(5):217-219.].

The effects of citrus flavonoids supplementation on endothelial function: A systematic review and dose-response meta-analysis of randomized clinical trials.

The present systematic review and dose-response meta-analysis was conducted to synthesize existing data from randomized clinical trials (RCTs) concerning the impact of citrus flavonoids supplementation (CFS) on endothelial function. Relevant RCTs were identified through comprehensive searches of the PubMed, ISI Web of Science, and Scopus databases up to May 30, 2023. Weighted mean differences and their corresponding 95% confidence intervals (CI) were pooled utilizing a random-effects model. A total of eight eligible RCTs, comprising 596 participants, were included in the analysis. The pooled data demonstrated a statistically significant augmentation in flow-mediated vasodilation (FMD) (2.75%; 95% CI: 1.29, 4.20; I2 = 87.3%; p < 0.001) associated with CFS compared to the placebo group. Furthermore, the linear dose-response analysis indicated that each increment of 200 mg/d in CFS led to an increase of 1.09% in FMD (95% CI: 0.70, 1.48; I2 = 94.5%; p < 0.001). The findings from the nonlinear dose-response analysis also revealed a linear relationship between CFS and FMD (Pnon-linearity = 0.903, Pdose-response <0.001). Our findings suggest that CFS enhances endothelial function. However, more extensive RTCs encompassing longer intervention durations and different populations are warranted to establish more precise conclusions.

Integrating a Fundus Camera with High-Frequency Ultrasound for Precise Ocular Lesion Assessment.

Ultrasound A-scan is an important tool for quantitative assessment of ocular lesions. However, its usability is limited by the difficulty of accurately localizing the ultrasound probe to a lesion of interest. In this study, a transparent LiNbO3 single crystal ultrasound transducer was fabricated, and integrated with a widefield fundus camera to guide the ultrasound local position. The electrical impedance, phase spectrum, pulse-echo performance, and optical transmission spectrum of the ultrasound transducer were validated. The novel fundus camera-guided ultrasound probe was tested for in vivo measurement of rat eyes. Anterior and posterior segments of the rat eye could be unambiguously differentiated with the fundus photography-guided ultrasound measurement. A model eye was also used to verify the imaging performance of the prototype device in the human eye. The prototype shows the potential of being used in the clinic to accurately measure the thickness and echogenicity of ocular lesions in vivo.

Cell Type-Specific Extracellular Vesicles and Their Impact on Health and Disease.

Extracellular vesicles (EVs), a diverse group of cell-derived exocytosed particles, are pivotal in mediating intercellular communication due to their ability to selectively transfer biomolecules to specific cell types. EVs, composed of proteins, nucleic acids, and lipids, are taken up by cells to affect a variety of signaling cascades. Research in the field has primarily focused on stem cell-derived EVs, with a particular focus on mesenchymal stem cells, for their potential therapeutic benefits. Recently, tissue-specific EVs or cell type-specific extracellular vesicles (CTS-EVs), have garnered attention for their unique biogenesis and molecular composition because they enable highly targeted cell-specific communication. Various studies have outlined the roles that CTS-EVs play in the signaling for physiological function and the maintenance of homeostasis, including immune modulation, tissue regeneration, and organ development. These properties are also exploited for disease propagation, such as in cancer, neurological disorders, infectious diseases, autoimmune conditions, and more. The insights gained from analyzing CTS-EVs in different biological roles not only enhance our understanding of intercellular signaling and disease pathogenesis but also open new avenues for innovative diagnostic biomarkers and therapeutic targets for a wide spectrum of medical conditions. This review comprehensively outlines the current understanding of CTS-EV origins, function within normal physiology, and implications in diseased states.

Chlorine-Induced Toxicity on Murine Cornea: Exploring the Potential Therapeutic Role of Antioxidants.

Chlorine (Cl2) exposure poses a significant risk to ocular health, with the cornea being particularly susceptible to its corrosive effects. Antioxidants, known for their ability to neutralize reactive oxygen species (ROS) and alleviate oxidative stress, were explored as potential therapeutic agents to counteract chlorine-induced damage. In vitro experiments using human corneal epithelial cells showed decreased cell viability by chlorine-induced ROS production, which was reversed by antioxidant incubation. The mitochondrial membrane potential decreased due to both low and high doses of Cl2 exposure; however, it was recovered through antioxidants. The wound scratch assay showed that antioxidants mitigated impaired wound healing after Cl2 exposure. In vivo and ex vivo, after Cl2 exposure, increased corneal fluorescein staining indicates damaged corneal epithelial and stromal layers of mice cornea. Likewise, Cl2 exposure in human ex vivo corneas led to corneal injury characterized by epithelial fluorescein staining and epithelial erosion. However, antioxidants protected Cl2-induced damage. These results highlight the effects of Cl2 on corneal cells using in vitro, ex vivo, and in vivo models while also underscoring the potential of antioxidants, such as vitamin A, vitamin C, resveratrol, and melatonin, as protective agents against acute chlorine toxicity-induced corneal injury. Further investigation is needed to confirm the antioxidants' capacity to alleviate oxidative stress and enhance the corneal healing process.

Insights into hippocampal perfusion using high-resolution, multi-modal 7T MRI.

We present a comprehensive study on the non-invasive measurement of hippocampal perfusion. Using high-resolution 7 tesla arterial spin labeling (ASL) data, we generated robust perfusion maps and observed significant variations in perfusion among hippocampal subfields, with CA1 exhibiting the lowest perfusion levels. Notably, these perfusion differences were robust and already detectable with 50 perfusion-weighted images per subject, acquired in 5 min. To understand the underlying factors, we examined the influence of image quality metrics, various tissue microstructure and morphometric properties, macrovasculature, and cytoarchitecture. We observed higher perfusion in regions located closer to arteries, demonstrating the influence of vascular proximity on hippocampal perfusion. Moreover, ex vivo cytoarchitectonic features based on neuronal density differences appeared to correlate stronger with hippocampal perfusion than morphometric measures like gray matter thickness. These findings emphasize the interplay between microvasculature, macrovasculature, and metabolic demand in shaping hippocampal perfusion. Our study expands the current understanding of hippocampal physiology and its relevance to neurological disorders. By providing in vivo evidence of perfusion differences between hippocampal subfields, our findings have implications for diagnosis and potential therapeutic interventions. In conclusion, our study provides a valuable resource for extensively characterizing hippocampal perfusion.

Single neurons in the thalamus and subthalamic nucleus process cardiac and respiratory signals in humans.

Visceral signals are constantly processed by our central nervous system, enable homeostatic regulation, and influence perception, emotion, and cognition. While visceral processes at the cortical level have been extensively studied using non-invasive imaging techniques, very few studies have investigated how this information is processed at the single neuron level, both in humans and animals. Subcortical regions, relaying signals from peripheral interoceptors to cortical structures, are particularly understudied and how visceral information is processed in thalamic and subthalamic structures remains largely unknown. Here, we took advantage of intraoperative microelectrode recordings in patients undergoing surgery for deep brain stimulation (DBS) to investigate the activity of single neurons related to cardiac and respiratory functions in three subcortical regions: ventral intermedius nucleus (Vim) and ventral caudalis nucleus (Vc) of the thalamus, and subthalamic nucleus (STN). We report that the activity of a large portion of the recorded neurons (about 70%) was modulated by either the heartbeat, the cardiac inter-beat interval, or the respiration. These cardiac and respiratory response patterns varied largely across neurons both in terms of timing and their kind of modulation. A substantial proportion of these visceral neurons (30%) was responsive to more than one of the tested signals, underlining specialization and integration of cardiac and respiratory signals in STN and thalamic neurons. By extensively describing single unit activity related to cardiorespiratory function in thalamic and subthalamic neurons, our results highlight the major role of these subcortical regions in the processing of visceral signals.

Patient Engagement With and Perspectives on a Mobile Health Home Spirometry Intervention: Mixed Methods Study.

BACKGROUND: Patient engagement attrition in mobile health (mHealth) remote patient monitoring (RPM) programs decreases program benefits. Systemic disparities lead to inequities in RPM adoption and use. There is an urgent need to understand patients' experiences with RPM in the real world, especially for patients who have stopped using the programs, as addressing issues faced by patients can increase the value of mHealth for patients and subsequently decrease attrition. OBJECTIVE: This study sought to understand patient engagement and experiences in an RPM mHealth intervention in lung transplant recipients. METHODS: Between May 4, 2020, and November 1, 2022, a total of 601 lung transplant recipients were enrolled in an mHealth RPM intervention to monitor lung function. The predictors of patient engagement were evaluated using multivariable logistic and linear regression. Semistructured interviews were conducted with 6 of 39 patients who had engaged in the first month but stopped using the program, and common themes were identified. RESULTS: Patients who underwent transplant more than 1 year before enrollment in the program had 84% lower odds of engaging (odds ratio [OR] 0.16, 95% CI 0.07-0.35), 82% lower odds of submitting pulmonary function measurements (OR 0.18, 95% CI 0.09-0.33), and 78% lower odds of completing symptom checklists (OR 0.22, 95% CI 0.10-0.43). Patients whose primary language was not English had 78% lower odds of engaging compared to English speakers (OR 0.22, 95% CI 0.07-0.67). Interviews revealed 4 prominent themes: challenges with devices, communication breakdowns, a desire for more personal interactions and specific feedback with the care team about their results, understanding the purpose of the chat, and understanding how their data are used. CONCLUSIONS: Care delivery and patient experiences with RPM in lung transplant mHealth can be improved and made more equitable by tailoring outreach and enhancements toward non-English speakers and patients with a longer time between transplant and enrollment. Attention to designing programs to provide personalization through supplementary provider contact, education, and information transparency may decrease attrition rates.

Characterization of persistent organic contaminants in the atmosphere of Gadani's ship breaking yards and its surrounding: Implications for sustainable ship recycling practices.

Gadani is internationally renowned for its extensive ship-breaking operations, positioning it as one of the globe's primary ship-breaking hubs. A comprehensive study was conducted to evaluate the presence of organic contaminants in the air within Gadani, encompassing the areas surrounding ship-breaking facilities, proximate residential settlements, and adjacent roadways. Passive air samplers were employed to collect a total of 30 air samples. The analytical results unveiled a notably elevated concentration of specific organic compounds, with a pronounced prevalence of polycyclic aromatic hydrocarbons (PAHs), short-chain chlorinated paraffins (SCCPs), and polychlorinated biphenyls (PCBs) at the ship-breaking yard. Notably, dichlorodiphenyltrichloroethanes (DDTs) and DDE were detected at substantially lower levels. In particular, sites in close proximity to ship-breaking activities exhibited elevated concentrations of PCBs (Σ7PCB 0.065429 to 7.345714 ng/sample), PAHs (Σ8PAH 2.44 to 134.23 ng/sample), and SCCPs (0.18 to 25.6 ng/sample). Conversely, DDTs and DDE demonstrated higher concentrations near residential settlements. The evaluation of Molecular Diagnostic Ratios for PAHs revealed anthracene/anthracene + phenanthrene ratios of 0.88, 0.69, and 0.5 for ship-breaking areas, roadside locations, and community surroundings, respectively. Furthermore, the benz[a]anthracene/benz-[a]anthracene + chrysene molecular ratios were measured at 0.77 (ship-breaking sites), 0.82 (roadside), and 0.83 (community), respectively. The molecular ratio of fluoranthene/fluoranthene + pyrene at ship-breaking sites was 0.23, while roadside and community ratios were 0.36 and 0.89, respectively. These findings underscore the significant contribution of ship-recycling activities to the atmospheric release of SCCPs, PCBs, and PAHs, emphasizing the global imperative for responsible ship recycling practices.

Integrating microbial abundance time series with fermentation dynamics of the rumen microbiome via mathematical modelling.

The rumen represents a dynamic microbial ecosystem where fermentation metabolites and microbial concentrations change over time in response to dietary changes. The integration of microbial genomic knowledge and dynamic modelling can enhance our system-level understanding of rumen ecosystem's function. However, such an integration between dynamic models and rumen microbiota data is lacking. The objective of this work was to integrate rumen microbiota time series determined by 16S rRNA gene amplicon sequencing into a dynamic modelling framework to link microbial data to the dynamics of the volatile fatty acids (VFA) production during fermentation. For that, we used the theory of state observers to develop a model that estimates the dynamics of VFA from the data of microbial functional proxies associated with the specific production of each VFA. We determined the microbial proxies using CowPi to infer the functional potential of the rumen microbiota and extrapolate their functional modules from KEGG (Kyoto Encyclopedia of Genes and Genomes). The approach was challenged using data from an in vitro RUSITEC experiment and from an in vivo experiment with four cows. The model performance was evaluated by the coefficient of variation of the root mean square error (CRMSE). For the in vitro case study, the mean CVRMSE were 9.8% for acetate, 14% for butyrate and 14.5% for propionate. For the in vivo case study, the mean CVRMSE were 16.4% for acetate, 15.8% for butyrate and 19.8% for propionate. The mean CVRMSE for the VFA molar fractions were 3.1% for acetate, 3.8% for butyrate and 8.9% for propionate. Ours results show the promising application of state observers integrated with microbiota time series data for predicting rumen microbial metabolism.

Imaging as an early biomarker to predict sensitivity to everolimus for progressive NF2-related vestibular schwannoma.

PURPOSE: NF2-related schwannomatosis (NF2) is characterized by bilateral vestibular schwannomas (VS) often causing hearing and neurologic deficits, with currently no FDA-approved drug treatment. Pre-clinical studies highlighted the potential of mTORC1 inhibition in delaying schwannoma progression. We conducted a prospective open-label, phase II study of everolimus for progressive VS in NF2 patients and investigated imaging as a potential biomarker predicting effects on growth trajectory. METHODS: The trial enrolled 12 NF2 patients with progressive VS. Participants received oral everolimus daily for 52 weeks. Brain imaging was obtained quarterly. As primary endpoint, radiographic response (RR) was defined as ≥ 20% decrease in target VS volume. Secondary endpoints included other tumors RR, hearing outcomes, drug safety and quality of life (QOL). RESULTS: Eight participants completed the trial and four discontinued the drug early due to significant volumetric VS progression. After 52 weeks of treatment, the median annual VS growth rate decreased from 77.2% at baseline to 29.4%. There was no VS RR and 3 of 8 (37.5%) participants had stable disease. Decreased or unchanged VS volume after 3 months of treatment was predictive of stabilization at 12 months. Seven of eight participants had stable hearing during treatment except one with a decline in word recognition score. Ten of twelve participants reported only minimal changes to their QOL scores. CONCLUSIONS: Volumetric imaging at 3 months can serve as an early biomarker to predict long-term sensitivity to everolimus treatment. Everolimus may represent a safe treatment option to decrease the growth of NF2-related VS in patients who have stable hearing and neurological condition. TRN: NCT01345136 (April 29, 2011).