Clinical Practice of High-Flow Nasal Cannula Therapy in ARDS Patients: A Cross-Sectional Survey of Respiratory Therapists.

Background: High-flow nasal cannula (HFNC) is an essential non-invasive oxygen therapy in acute respiratory distress syndrome (ARDS) patients. Despite its wide use, research assessing the knowledge, practice, and barriers to using HFNC among respiratory therapists (RT) is lacking. Methods: A cross-sectional questionnaire was conducted among RTs in Saudi Arabia between December 19, 2022, and July 15, 2023. Data were analyzed as means and standard deviation or frequency and percentages. A Chi-square test was used to compare the differences between groups. Results: A total of 1001 RTs completed the online survey. Two-thirds of the respondents 659 (65.8%) had received training in using HFNC and 785 (78.4%) had used HFNC in clinical settings. The top conditions for HFNC indication were COVID-19 (78%), post-extubation (65%), and do-not-intubate patients (64%). Participants strongly agreed that helping maintain conversation and eating abilities (32.95%) and improving shortness of breath (34.1%) were advantages of HFNC. Surprisingly, 568 (57%) of RT staff did not follow a protocol for HFNC with ARDS patients. When starting HFNC, 40.2% of the participants started with FiO2 of 61% to 80%. Additionally, high percentages of RT staff started with a flow rate between 30 L/minute and 40 L/minute (40.6%) and a temperature of 37°C (57.7%). When weaning ARDS patients, 482 (48.1%) recommended first reducing gas flow by 5-10 L/minute every two to four hours. Moreover, 549 (54.8%) believed that ARDS patients could be disconnected from HFNC if they achieved a flow rate of <20 L/minute and FiO2 of <35%. Lack of knowledge was the most common challenge concerning HFNC implementation. Conclusion: The findings revealed nuanced applications marked by significant endorsement in certain clinical scenarios and a lack of protocol adherence, underscoring the need for uniform, evidence-based guidelines and enhanced training for RTs. Addressing these challenges is pivotal to optimizing the benefits of HFNC across varied clinical contexts.

Integrated management of groundwater quantity, physicochemical properties, and microbial quality in West Nile delta using a new MATLAB code and geographic information system mapping.

Groundwater is an excellent alternative to freshwater for drinking, irrigation, and developing arid regions. Agricultural, commercial, industrial, residential, and municipal activities may affect groundwater quantity and quality. Therefore, we aimed to use advanced methods/techniques to monitor the piezometric levels and collect groundwater samples to test their physicochemical and biological characteristics. Our results using software programs showed two main types of groundwater: the most prevalent was the Na-Cl type, which accounts for 94% of the groundwater samples, whereas the Mg-Cl type was found in 6% of samples only. In general, the hydraulic gradient values, ranging from medium to low, could be attributed to the slow movement of groundwater. Salinity distribution in groundwater maps varied between 238 and 1350 mg L-1. Although lower salinity values were observed in northwestern wells, higher values were recorded in southern ones. The collected seventeen water samples exhibited brackish characteristics and were subjected to microbial growth monitoring. Sample WD12 had the lowest total bacterial count (TBC) of 4.8 ± 0.9 colony forming unit (CFU mg L-1), while WD14 had the highest TBC (7.5 ± 0.5 CFU mg L-1). None of the tested water samples, however, contained pathogenic microorganisms. In conclusion, the current simulation models for groundwater drawdown of the Quaternary aquifer system predict a considerable drawdown of water levels over the next 10, 20, and 30 years with the continuous development of the region.

Ameliorative impacts of propolis against testicular toxicity promoted by doxorubicin.

Background and Aim: Doxorubicin (DOX) is often used as a chemotherapeutic agent, although it may damage testicular functions. This study was designed to investigate the protective effects of propolis on testicular histological changes, semen parameters, and testosterone concentrations as a means of protecting against testicular damage caused by DOX chemotherapy. Materials and Methods: Forty-eight male Wistar rats were divided into four groups with 12 animals per group. The first group served as the control. Rats in the second group were administered 4 mg/kg DOX. The third group was administered 4 mg/kg of DOX and 30 mg/kg b.w. propolis. The fourth group was orally dosed daily with 30 mg/kg b.w. propolis. Results: DOX treatment resulted in a significantly decreased weight gain (WG) rate compared with the control, whereas DOX + propolis resulted in improved WG and returned to the normal range. Testosterone levels were comparable among the experimental groups, with a significant increase in the propolis-treated group. In addition, DOX-treated groups exhibited a remarkable depletion in sperm counts, motility, and viability compared to the other groups. Conclusion: Most of the histological and hormonal changes resulting from the toxicity of DOX returned to almost normal after treatment of rats with the aqueous extract of propolis, indicating that propolis ameliorated the effects of DOX poisoning on testicular function in male rats.

Strategies for Inducing and Validating Zinc Deficiency and Zinc Repletion.

Given the growing interest in the role of zinc in the onset and progression of diseases, there is a crucial demand for reliable methods to modulate zinc homeostasis. Using a dietary approach, we provide validated strategies to alter whole-body zinc in mice, applicable across species. For confirmation of zinc status, animal growth rates as well as plasma and urine zinc levels were evaluated. The accessible and cost-effective methodology outlined will increase scientific rigor, ensuring reproducibility in studies exploring the impact of zinc deficiency and repletion on the onset and progression of diseases.

Durlobactam, a Diazabicyclooctane ß-Lactamase Inhibitor, Inhibits BlaC and Peptidoglycan Transpeptidases of Mycobacterium tuberculosis.

Peptidoglycan synthesis is an underutilized drug target in Mycobacterium tuberculosis (Mtb). Diazabicyclooctanes (DBOs) are a class of broad-spectrum ß-lactamase inhibitors that also inhibit certain peptidoglycan transpeptidases that are important in mycobacterial cell wall synthesis. We evaluated the DBO durlobactam as an inhibitor of BlaC, the Mtb ß-lactamase, and multiple Mtb peptidoglycan transpeptidases (PonA1, LdtMt1, LdtMt2, LdtMt3, and LdtMt5). Timed electrospray ionization mass spectrometry (ESI-MS) captured acyl-enzyme complexes with BlaC and all transpeptidases except LdtMt5. Inhibition kinetics demonstrated durlobactam was a potent and efficient DBO inhibitor of BlaC (KI app 9.2 ± 0.9 µM, k2/K 5600 ± 560 M-1 s-1) and similar to clavulanate (KI app 3.3 ± 0.6 µM, k2/K 8400 ± 840 M-1 s-1); however, durlobactam had a lower turnover number (tn = kcat/kinact) than clavulanate (1 and 8, respectively). KI app values with durlobactam and clavulanate were similar for peptidoglycan transpeptidases, but ESI-MS captured durlobactam complexes at more time points. Molecular docking and simulation demonstrated several productive interactions of durlobactam in the active sites of BlaC, PonA1, and LdtMt2. Antibiotic susceptibility testing was conducted on 11 Mtb isolates with amoxicillin, ceftriaxone, meropenem, imipenem, clavulanate, and durlobactam. Durlobactam had a minimum inhibitory concentration (MIC) range of 0.5-16 µg/mL, similar to the ranges for meropenem (1-32 µg/mL) and imipenem (0.5-64 µg/mL). In ß-lactam + durlobactam combinations (1:1 mass/volume), MICs were lowered 4- to 64-fold for all isolates except one with meropenem-durlobactam. This work supports further exploration of novel ß-lactamase inhibitors that target BlaC and Mtb peptidoglycan transpeptidases.

Temperature-resilient and sustainable Mn-MOF oxidase-like nanozyme (UoZ-4) for total antioxidant capacity sensing in some citrus fruits: Breaking the temperature barrier.

Current nanozyme applications rely heavily on peroxidase-like nanozymes and are limited to a specific temperature range, despite notable advancements in nanozyme development. In this work, we designed novel Mn-based metal organic frameworks (UoZ-4), with excellent oxidase mimic activity towards common substrates. UoZ-4 showed excellent oxidase-like activity (with Km 0.072 mM) in a wide range of temperature, from 10 °C to 100 °C with almost no activity loss, making it a very strong candidate for psychrophilic and thermophilic applications. Ascorbic acid, cysteine, and glutathione could quench the appearance of the blue color of oxTMB, led us to design a visual-based sensing platform for detection of total antioxidant capacity (TAC) in cold, mild and hot conditions. The visual mode successfully assessed TAC in citrus fruits with satisfactory recovery and precisions. Cold/hot adapted and magnetic property will broaden the horizon of nanozyme applications and breaks the notion of the temperature limitation of enzymes.

Suillus: an emerging model for the study of ectomycorrhizal ecology and evolution.

Research on mycorrhizal symbiosis has been slowed by a lack of established study systems. To address this challenge, we have been developing Suillus, a widespread ecologically and economically relevant fungal genus primarily associated with the plant family Pinaceae, into a model system for studying ectomycorrhizal (ECM) associations. Over the last decade, we have compiled extensive genomic resources, culture libraries, a phenotype database, and protocols for manipulating Suillus fungi with and without their tree partners. Our efforts have already resulted in a large number of publicly available genomes, transcriptomes, and respective annotations, as well as advances in our understanding of mycorrhizal partner specificity and host communication, fungal and plant nutrition, environmental adaptation, soil nutrient cycling, interspecific competition, and biological invasions. Here, we highlight the most significant recent findings enabled by Suillus, present a suite of protocols for working with the genus, and discuss how Suillus is emerging as an important model to elucidate the ecology and evolution of ECM interactions.

Graphene oxide-based nanocomposites for outstanding eco-friendly antifungal potential against tomato phytopathogens.

To obtain the collaborative antifungal potential of nanocomposites conjugated with graphene oxide (GO), a combination of GO with chitosan (CS/GO) and GO with chitosan (CS) and polyaniline (PANI/CS/GO) was carried out. The synthesized GO-nanocomposites were recognized by several techniques. Vanillin (Van.) and cinnamaldehyde (Cinn.) were loaded on the prepared nanocomposites as antioxidants through a batch adsorption process. In vitro release study of Van. and Cinn. from the nanocomposites was accomplished at pH 7 and 25°C. The antimicrobial activity of GO, CS/GO, and PANI/CS/GO was studied against tomato Fusarium oxysporum (FOL) and Pythium debaryanum (PYD) pathogens. The loaded ternary composite PANI/CS/GO exhibited the best percent of reduction against the two pathogens in vitro studies. The Greenhouse experiment revealed that seedlings' treatment by CS/GO/Van. and PANI/CS/GO/Van significantly lowered both disease index and disease incidence. The loaded CS/GO and PANI/CS/GO nanocomposites had a positive effect on lengthening shoots. Additionally, when CS/GO/Cinn., CS/GO/Van. and PANI/CS/GO/Van. were used, tomato seedlings' photosynthetic pigments dramatically increased as compared to infected control. The results show that these bio-nanocomposites can be an efficient, sustainable, nontoxic, eco-friendly, and residue-free approach for fighting fungal pathogens and improving plant growth.

Key lifestyles and health outcomes across 16 prevalent chronic diseases: A network analysis of an international observational study.

Background: Central and bridge nodes can drive significant overall improvements within their respective networks. We aimed to identify them in 16 prevalent chronic diseases during the coronavirus disease 2019 (COVID-19) pandemic to guide effective intervention strategies and appropriate resource allocation for most significant holistic lifestyle and health improvements. Methods: We surveyed 16 512 adults from July 2020 to August 2021 in 30 territories. Participants self-reported their medical histories and the perceived impact of COVID-19 on 18 lifestyle factors and 13 health outcomes. For each disease subgroup, we generated lifestyle, health outcome, and bridge networks. Variables with the highest centrality indices in each were identified central or bridge. We validated these networks using nonparametric and case-dropping subset bootstrapping and confirmed central and bridge variables' significantly higher indices through a centrality difference test. Findings: Among the 48 networks, 44 were validated (all correlation-stability coefficients >0.25). Six central lifestyle factors were identified: less consumption of snacks (for the chronic disease: anxiety), less sugary drinks (cancer, gastric ulcer, hypertension, insomnia, and pre-diabetes), less smoking tobacco (chronic obstructive pulmonary disease), frequency of exercise (depression and fatty liver disease), duration of exercise (irritable bowel syndrome), and overall amount of exercise (autoimmune disease, diabetes, eczema, heart attack, and high cholesterol). Two central health outcomes emerged: less emotional distress (chronic obstructive pulmonary disease, eczema, fatty liver disease, gastric ulcer, heart attack, high cholesterol, hypertension, insomnia, and pre-diabetes) and quality of life (anxiety, autoimmune disease, cancer, depression, diabetes, and irritable bowel syndrome). Four bridge lifestyles were identified: consumption of fruits and vegetables (diabetes, high cholesterol, hypertension, and insomnia), less duration of sitting (eczema, fatty liver disease, and heart attack), frequency of exercise (autoimmune disease, depression, and heart attack), and overall amount of exercise (anxiety, gastric ulcer, and insomnia). The centrality difference test showed the central and bridge variables had significantly higher centrality indices than others in their networks (P < 0.05). Conclusion: To effectively manage chronic diseases during the COVID-19 pandemic, enhanced interventions and optimised resource allocation toward central lifestyle factors, health outcomes, and bridge lifestyles are paramount. The key variables shared across chronic diseases emphasise the importance of coordinated intervention strategies.

Prevalence and Correlates of Depression Among Pregnant Women at King Abdulaziz Medical City: A Tertiary Hospital in Riyadh, Saudi Arabia.

BACKGROUND: Women have a higher likelihood of experiencing depression during pregnancy due to the significant physiological and mental changes that occur during this critical period. The frequency of antenatal depression varies globally according to socioeconomic, healthcare, and cultural influences. The objective of this study is to investigate the prevalence of depression among pregnant women in Riyadh, Saudi Arabia. MATERIALS AND METHODS: Women who were pregnant and who had undergone screening for depression were included in this cohort study that was conducted at King Abdulaziz Medical City (KAMC). Using a non-probability convenience sample technique, data was obtained from the hospital record system. Statistical significance was determined using Fisher's exact test and student's t-test, which analyzed demographic, clinical, demographic, and obstetric information. Significance was determined by a P-value that was lower than 0.05. RESULTS: Among 367 people surveyed, the prevalence of depression was 2.5%. This is much lower than rates seen both globally and in Saudi Arabia. The majority were married and non-smokers with a high post-delivery BMI. A significant association was observed between depression and previous psychiatric diagnoses, while no significant relationships were found with gestational age, complications, chronic illnesses, or referral sources. CONCLUSION: The research shows that the rate of perinatal depression among women in Riyadh is much lower than the average, highlighting the critical role of cultural factors and the need for validated, culturally sensitive screening tools. Recommendations for future research include longitudinal studies and the development of culturally tailored interventions to enhance the detection and management of depression during pregnancy, integrating mental health care into routine antenatal services.

Multisite Pain and Intensity were Associated with History Fall among Older Adults: A Cross-Sectional Study.

Purpose: This study examined the independent associations among multisite pain, pain intensity, and the risk of falls, including a history of falls in the previous 12 months and frequent falls (≥ two falls vs one or two falls) among community-dwelling older adults. Methods: A cross-sectional design from Wave 2 of the National Social Life, Health, and Aging Project was used. Data on pain intensity and location (45 sites) over the past 4 weeks were collected. Multisite pain was categorized into four groups: none, one, two, and three or more sites. The main outcomes of falls were a history of falls and frequent falls. The covariates included age, sex, race, body mass index, education, medications, and comorbidities. Results: Among 3,196 participants in Wave 2, 2,697 were included because of missing key variables related to pain and fall history. The prevalence of falls and frequent falls were 30.3% (n = 817) and 12.6% (n = 339), respectively. Multisite pain at ≥ three sites (odds ratio (OR) 2.04, confidence interval (CI) [1.62, 2.57]; p < 0.001) and two sites (OR 1.72, 95% CI [1.30, 2.27]; p < 0.001) was significantly associated with an increased risk of falls. An increase in pain intensity was significantly associated with an increased risk of fall (OR 1.28, 95% CI [1.15, 1.44], p < 0.001), independent of multisite pain. Multisite pain at ≥3 sites (OR 2.19, 95% CI [1.56, 3.07], p < 0.001) and 2 sites (OR 1.54, 95% CI [1.01, 2.34], p = 0.045) was associated with an increased risk of frequent falls. An increase in pain intensity was associated with risk of frequent falls (OR 1.64, 95% CI [1.40, 1.91], p < 0.001), independent of multisite pain. Conclusion: Multisite pain and pain intensity were associated with a history of falls and frequent falls among older adults, emphasizing the need for routine pain evaluation to develop fall prevention strategies in this population.

Methanol intoxication in the central region of Saudi Arabia: Five case studies.

Outbreaks of methanol poisoning have been described in the medical literature worldwide. However, the few outbreaks that have occurred in Saudi Arabia remain undocumented. This is especially noteworthy in light of the fact that Saudi Arabia is among the countries that explicitly prohibit the usage of alcoholic beverages and recreational drugs. Herein, we describe five cases of methanol poisoning in Saudi Arabia. The first three comprise patients admitted to the emergency room (ER) with signs of methanol toxicity, such as heart palpitations, vomiting, and blurred vision; otherwise, those patients were considered medically free. The remaining two cases were examined postmortem. A headspace gas chromatography-flame ionization detector was used to test blood, vitreous humor, and urine samples for methanol. Specific lethal concentrations of methanol were defined based on published case studies as 23-740 mg/dL in blood and 12-396 mg/dL in vitreous humor. In postmortem cases of our present study, samples exhibited lethal concentrations: 118 and 257 mg/dL in blood, 116.3 and 283 mg/dL in vitreous humor. In ER cases, methanol concentrations in urine samples were lower, at 7.5, 9.1, and 20.9 mg/dL; however, toxic symptoms were still observed. These case studies indicate that it is necessary to raise community awareness about the risk of methanol poisoning in order to minimize future poisoning epidemics.

Exploring the Economic Aspects of Hospitals: A Comprehensive Examination of Relevant Factors.

Financial limitations in the hospital industry have the potential to exacerbate healthcare disparities, impede investments in cutting-edge medical treatments, as well as impair patient outcomes. The interdependent connection between a hospital economy and the general well-being of the community highlights the necessity of careful financial oversight and inventive healthcare policies. Effective collaboration among policymakers, healthcare administrators, and stakeholders is imperative in the development of sustainable economic models that give equal weight to fiscal prudence and optimal patient outcomes. This article aims to underscore the pivotal importance of strategic fund allocation guided by hospital administrators, accentuating several key initiatives capable of revolutionizing healthcare delivery and elevating the institution's stature within the medical community. The other important aspects discussed here are fund allocation in hospitals, the boom of online consultations, and emphasis on the use of sustainable and cost-effective modalities of energy.

Temperature, pressure, and duration impacts on the optimal stiffening of carbonates aged in diammonium phosphate solution.

Diammonium phosphate (DAP) has been proven effective in improving the stiffness of weak or acid-damaged carbonates, thereby preserving hydraulic fracture conductivity. The reaction between DAP and calcite in chalk formations primarily produces hydroxyapatite (HAP), which is stiffer than calcite. However, the optimal reaction outcomes vary greatly with factors such as DAP concentration and reaction conditions. This study investigated the DAP-calcite reaction duration, pressure, and temperature effects on the stiffness magnitude of soft Austin chalk. Also, the catalyst effect and depth of HAP formation were examined. The study involved the assessment of stiffness non-destructively (impulse hammering), mineralogy (XRD, SEM), and elemental composition (XRF). The study tested 15 different DAP-chalk reaction variations, where the pressure, temperature, aging time and catalyst addition were modified in each case. The samples' elastic stiffness distributions were then collected and compared to the pre-reaction ones. The results showed that the elastic stiffness increased in all treated samples, with an 181% maximum increase achieved after 72 h at 6.9 MPa and 75 °C. However, the pressure effect was minor compared to the temperature. The SEM images revealed different HAP morphology corresponding to different treatment conditions. Although the treated samples showed an increased intensity of phosphorus throughout the entire sample, the near-surface zone (4-6 mm) was the most affected, as inferred from the XRF elemental analysis. The study's findings can help optimize hydraulic fracturing operations in weak carbonate reservoirs, improving production rates and overall well performance.

Enhancing the Antiproliferative Activity of Perillyl Alcohol against Glioblastoma Cell Lines through Synergistic Formulation with Natural Oils.

BACKGROUND: Due to its volatility, photostability, and gastrointestinal toxicity, Perillyl Alcohol (POH), a monoterpenoid component of various plant species, is a chemotherapeutic drug with insufficient efficacy. Many naturally occurring bioactive compounds have well-known antiproliferative properties, including sefsol, jojoba, tea tree, and moringa oils. OBJECTIVE: This study sought to develop an oil-based Self Nanoemulsifying Drug Delivery System (SNEDDS) using tween 80 as the surfactant and Dimethyl Sulfoxide (DMSO) or Polyethylene Glycol (PEG) 400 as the cosurfactant; the oils were used in a range of 10-20% to boost POH's anticancer efficacy. METHODS: The formulations' size, charge, and impact on the viability of glioma cell lines, ANGM-CSS and A172, were evaluated. RESULTS: The developed SNEDDS formulations ranged from 3 nm to 362 nm in size, with electronegative surface charges between 5.05 and 17.0 mV and polydispersity indices between 0.3 and 1.0. CONCLUSION: The findings indicated that the antiproliferative effect of POH-loaded Nanoemulsion (NE) could be used as a possible anticancer therapy for glioblastoma in vitro, particularly when paired with the tested natural oils. Before asserting that this delivery technique is appropriate for glioblastoma therapy, additional in vitro and in vivo investigations are required.

Factors associated with applicant performance on the Saudi Pharmacist Licensure Examination (SPLE).

Background: Limited data are available on factors that are associated with passing rates for the Saudi Pharmacist Licensure Examination (SPLE). The aim of this study is to investigate student characteristics and academic performance characteristics that may predict their success on SPLE. Methods: This was a single-institution retrospective cohort study, which included pharmacy graduates from 2019 to 2021. Demographic, academic, and SPLE data were collected for each graduate. Binary logistic regression was used to explore the association between potential predictors and first-time SPLE pass status. A stepwise regression was then performed to develop multiple logistic models. Results: A total of 494 graduates were included in the study. Females, PharmD graduates, and on-time graduation had higher odds of passing SPLE (P = 0.0065, P = 0.0003, and P < 0.0001, respectively). For each 0.5 increase in GPA, the odds of passing SPLE increase by 3.5 times (OR 3.53; 95 % CI, 2.83-4.42; P < 0.0001). Of the tests taken prior to university admission, the overall high school score, general aptitude test (GAT) score, and qualifying score were significantly associated with higher SPLE first-time pass rates. When multiple logistic regression analysis was performed, GPA and GAT scores were the only significant predictors for higher SPLE first-time pass rates (P < 0.0001 and P = 0.0002, respectively). Conclusion: The current research has shown that there is an association between higher SPLE first-time pass rates and several factors, most importantly the GPA and GAT score. Further research is needed, as it has the potential to inform the decision when reviewing pharmacy admission criteria.

A novel ratiometric design of microfluidic paper-based analytical device for the simultaneous detection of Cu2+ and Fe3+ in drinking water using a fluorescent MOF@tetracycline nanocomposite.

The regular and on-site monitoring of ions in drinking water is essential for safeguarding public health, ensuring high water quality, and preserving the ecological balance of aquatic ecosystems. Thus, developing a portable analytical device for the rapid, cost-effective, and visual on-site detection of multiple environmental pollutants is notably significant. In the present work, a novel ratiometric microfluidic paper-based analytical device (µPAD) was designed and developed for the simultaneous detection of Fe3+ and Cu2+ ions in water samples taking advantages from built-in masking zone. The µPAD was functionalized with a greenish-yellow fluorescent Zn-based metal-organic framework@tetracycline (FMOF-5@TC) nanocomposite, and the ratiometric design was based on the change in emission color from greenish yellow (FMOF-5@TC) to blue (FMOF-5). The µPAD consisted of one sample zone linked to two detection zones via two channels: the first channel was for the detection of both ions, while the second was intended for detecting only Cu2+ ions and comprised a built-in masking zone to remove Fe3+ ions prior to reaching the detection zone. The corresponding color changes were recorded with the aid of a smartphone and RGB calculations. The linear ranges were 0.1-80 µM for Cu2+ and 0.2-160 µM for Fe3+, with limits of detection of 0.027 and 0.019 µM, respectively. The simple µPAD design enabled the simultaneous detection of Cu2+ and Fe3+ ions in drinking water samples with excellent accuracy and precision, with spike recoveries of 81.28-96.36% and 83.01-102.33% for Cu2+ and Fe3+, respectively.

Strategies for Inducing and Validating Zinc Deficiency and Zinc Repletion.

Given the growing interest in the role of zinc in the onset and progression of diseases, there is a crucial demand for reliable methods to modulate zinc homeostasis. Using a dietary approach, we provide validated strategies to alter whole-body zinc in mice, applicable across species. For confirmation of zinc status, animal growth rates as well as plasma and urine zinc levels were evaluated. The accessible and cost-effective methodology outlined will increase scientific rigor, ensuring reproducibility in studies exploring the impact of zinc deficiency and repletion on the onset and progression of diseases.

Comprehensive metabolomics analysis reveals novel biomarkers and pathways in falsely suspected glutaric aciduria Type-1 newborns.

BACKGROUND: Glutaric aciduria type-1 (GA-1) is a rare metabolic disorder due to glutaryl coenzyme A dehydrogenase deficiency, causing elevated levels of glutaryl-CoA and its derivatives. GA-1 exhibits symptoms like macrocephaly, developmental delays, and movement disorders. Timely diagnosis through genetic testing and newborn screening is crucial. However, in some cases, transiently elevated level of glutarylcarnitine (C5DC) challenges accurate diagnosis, highlighting the need for alternative diagnostic methods, like mass spectrometry-based untargeted metabolomics, to identify additional biomarkers for distinguishing falsely suspected GA-1 from healthy newborns. METHODOLOGY: DBS samples from falsely suspected GA-1 newborns (n = 47) and matched control were collected through the NBS program. Untargeted metabolomics using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) was performed to enable biomarker and pathway investigations for significantly altered metabolites. RESULTS: 582 and 546 were up- and down-regulated metabolites in transient GA-1. 155 endogenous metabolites displayed significant variations compared to the control group. Furthermore, our data identified novel altered metabolic biomarkers, such as N-palmitoylcysteine, heptacarboxyporphyrin, 3-hydroxylinoleoylcarnitine, and monoacylglyceride (MG) (0:0/20:1/0:0), along with perturbed metabolic pathways like sphingolipid and thiamine metabolism associated with the transient elevated C5DC levels in DBS samples. CONCLUSIONS: A distinct metabolic pattern linked to the transient C5DC elevation in newborns was reported to enhance the prediction of the falsely positive cases, which could help avoiding unnecessary medical treatments and minimizing the financial burdens in the health sector.