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Colorectal cancer (CRC) is a major health problem worldwide and is usually detected in advanced stages, although it is highly treatable with early detection. The aim of this study was to examine the serum levels of various cytokines involved in the pathogenesis of CRC. The study included 29 patients and 30 healthy volunteers. Blood samples were collected twice from the patient group, before and after surgery, and these samples were evaluated for interleukin (IL) 4, 10, 23r, 37, 38, 40 and interferon (IFN) gamma levels. The results showed that IL-4 and IL-38 levels were significantly lower in the preoperative serum samples of the patient group compared to the control group (p < 0.001 and p = 0.01, respectively), while IL-4, IL-10, IL-38 and IL-40 levels increased significantly in the postoperative period (p = 0.004, p = 0.02, p = 0.03 and p = 0.004, respectively). These findings may contribute to the development of immunotherapy agents in the treatment of CRC. However, comprehensive studies on larger patient groups are needed to fully understand the role of cytokines in CRC pathogenesis. [ABSTRACT FROM AUTHOR]

Carnosine is an endogenous dipeptide that buffers intracellular pH and quenches toxic products of lipid peroxidation. Used as a dietary supplement, it also supports exercise endurance. However, the accumulation and distribution of carnosine after supplementation has not been rigorously evaluated. To do this, we randomized a cohort to receive daily supplements of either placebo or carnosine (2 g/day). Blood and urine samples were collected twice over the subsequent 12 week supplementation period and we measured levels of red blood cell (RBC) carnosine, urinary carnosine, and urinary carnosine-propanol and carnosine-propanal conjugates by LC/MS–MS. We found that, when compared with placebo, supplementation with carnosine for 6 or 12 weeks led to an approximate twofold increase in RBC carnosine, while levels of urinary carnosine increased nearly sevenfold. Although there were no changes in the urinary levels of carnosine propanol, carnosine propanal increased nearly twofold. RBC carnosine levels were positively associated with urinary carnosine and carnosine propanal levels. No adverse reactions were reported by those in the carnosine or placebo arms, nor did carnosine supplementation have any effect on kidney, liver, and cardiac function or blood electrolytes. In conclusion, irrespective of age, sex, or BMI, oral carnosine supplementation in humans leads to its increase in RBC and urine, as well as an increase in urinary carnosine-propanal. RBC carnosine may be a readily accessible pool to estimate carnosine levels. Clinical trial registration: This study is registered with ClinicalTrials.gov (Nucleophilic Defense Against PM Toxicity (NEAT Trial)—Full Text View—ClinicalTrials.gov), under the registration: NCT03314987. [ABSTRACT FROM AUTHOR]

This study aimed to determine the sequence type (ST) of Bartonella henselae infecting small Indian mongooses from Saint Kitts via multi-locus sequence typing (MLST). This investigation used stored EDTA blood (n = 22) samples from mongooses previously identified as positive for B. henselae. Chocolate agar plates were enriched with Bartonella alpha-Proteobacteria growth medium (BAPGM) to culture and isolate Bartonella from the blood samples. To perform MLST, DNA was extracted and purified from isolates followed by amplification by conventional PCR (300–500 bp) for eight genes (16S rDNA, batR, gltA, groEL, ftsZ, nlpD, ribC, and rpoB). Bartonella henselae STs were deposited in the PubMLST repository. Out of 22 B. henselae-positive blood samples, isolates were obtained from 12 mongooses (54.5%; 12/22). Each mongoose was infected with one ST. The studied mongoose population was infected with sequence types ST2, ST3, ST8, and a novel ST represented by ST38. Bartonella henselae ST2, ST3 and ST8 infecting mongooses are known to circulate in humans and cats, with ST2 and ST8 associated with Cat Scratch Disease (bartonellosis) in humans. The results presented herein denote the circulation of B. henselae STs with zoonotic potential in mongooses with risk of B. henselae transmission to humans. [ABSTRACT FROM AUTHOR]

Purpose: To determine if 7d of New Zealand blackcurrant (NZBC) extract alters the heat shock, inflammatory and apoptotic response during prolonged exertional-heat stress. Methods: Ten men (Age: 29 ± 2 years, Stature: 1.82 ± 0.02 m, Mass: 80.3 ± 2.7 kg, V̇O2max: 56 ± 2 mL·kg−1·min−1) ingested two capsules of CurraNZ™ (NZBC extract: 210 mg anthocyanins·day−1) or PLACEBO for 7d prior to 1 h treadmill run (65% V̇O2max) in hot ambient conditions (34 °C/40% RH). Blood samples were collected before (Pre), immediately after (Post), 1 h after (1-Post), and 4 h after (4-Post) exercise. Heat shock proteins (HSP90, HSP70, HSP32) were measured in plasma. HSP and protein markers of inflammatory capacity (TLR4, NF-κB) and apoptosis (BAX/BCL-2, Caspase 9) were measured in peripheral blood mononuclear cells (PBMC). Results: eHSP32 was elevated at baseline in NZBC(+ 31%; p < 0.001). In PLACEBO HSP32 content in PBMC was elevated at 4-Post(+ 98%; p = 0.002), whereas in NZBC it fell at Post(− 45%; p = 0.030) and 1-Post(− 48%; p = 0.026). eHSP70 was increased at Post in PLACEBO(+ 55.6%, p = 0.001) and NZBC (+ 50.7%, p = 0.010). eHSP90 was increased at Post(+ 77.9%, p < 0.001) and 1-Post(+ 73.2%, p < 0.001) in PLACEBO, with similar increases being shown in NZBC (+ 49.0%, p = 0.006 and + 66.2%, p = 0.001; respectively). TLR4 and NF-κB were both elevated in NZBC at PRE(+ 54%, p = 0.003 and + 57%, p = 0.004; respectively). Main effects of study condition were also shown for BAX/BCL-2(p = 0.025) and Caspase 9 (p = 0.043); both were higher in NZBC. Conclusion: 7d of NZBC extract supplementation increased eHSP32 and PBMC HSP32 content. It also increased inflammatory and apoptotic markers in PBMC, suggesting that NZBC supports the putative inflammatory response that accompanies exertional-heat stress. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor 21 (FGF21), known for its metabolic effects, is a potential target for treating diabetes. This study aimed to assess the FGF21 levels and insulin resistance index after resistance and endurance training in the male diabetic rat's heart tissue. Twenty-four streptozotocin-induced diabetic rats have been divided into four groups randomly: endurance training (6), resistance training (6), sham (6), and healthy (6). The endurance training group trained on the treadmill 5 sessions/week for 4 weeks, while the resistance training group trained 6 sessions/week on the ladder. Before and following the first and last training sessions, blood samples had been collected to measure FBS, FBI, and HOMA. Following the final training session, heart tissue was lysed, and we determined the level of FGF21 by ELISA technique. Within- and between-group differences were measured in FBS, FBI, and HOMA-IR through analyzing data using pairwise samples T tests and repeated-measure ANOVA test respectively and the differences in FGF21 levels between groups through a one-way ANOVA test through SPSS software. The resistance training group had more FGF21 protein than the other groups. The endurance and resistance training groups did not differ significantly (P = 0.249). However, there was a significant difference from the sham group (P = 0.008). In addition, fasting blood sugar level and insulin resistance index reduced significantly in both groups of endurance training (P = 0.001, P = 0.005) and resistance training (P = 0.004, P = 0.01), and there were no significant differences between groups (P > 0.05). Both endurance and resistance training reduce fasting blood sugar and insulin resistance index. Furthermore, resistance training increases the amount of FGF21 in the heart tissue. However, there are no differences with endurance training. [ABSTRACT FROM AUTHOR]

A long-range surface plasmon biosensor (LRSPR) using the 2S2G/Teflon/Au MXene/Sensing medium (SM) is proposed for improve the imaging sensitivity. Here, the MXene layer is used to improve imaging sensitivity and protect against unwanted oxidation of Au layer. MXene having formula is Ti3C2Tx layered materials with hydrophilic nature, better stability, good conductivity and large surface area. The proposed LRSPR uses the high adsorption efficiency and high resolution. Numerically investigate the imaging sensitivity compared to the conventional surface plasmon sensor (cSPR) as well as systematic layer of proposed LRSPR sensor. The maximum imaging sensitivity of 10,465/RIU at 1.35 based RI of plasma sensing medium is achieved. The maximum electric field normalized at the interface between the Teflon-Au layer in the proposed sensor and the Au/MXene layer in the cSPR sensor. For the proposed LRSPR sensor, the penetration depth (PD) of the field into the sensing medium of 611.7 nm and 806.13 nm is obtained at Au-SM and MXene-SM interface for the sensing medium of 1.337 and 1.350. In addition, the figure of merit (FoM) as 193/RIU and 275.6/RIU is exhibited for the same sensing medium. [ABSTRACT FROM AUTHOR]

The present work focuses on the detection of dengue virus using a proposed copper (Cu) and black phosphorus (BP)–based SPR sensor. This proposed sensor is capable of detecting normal and infected blood samples containing plasma, platelets and hemoglobin. We studied the performance parameter at optimized Cu layer thickness of the proposed sensor by calculating that the maximum sensitivity is 150.55°/RIU, 226.73°/RIU and 295.58°/RIU at Rmin values with 57 nm, 57 nm and 51 nm thickness of Cu layer for the detection of plasma, platelet and hemoglobin in the blood sample of dengue malaria. The properties of BP combined with the unique plasmonic properties of SPR sensors can result in enhanced interactions between surface plasmons and incident light. These results are intended for improved sensitivity and remarkable figure of merit (FoM). We also calculated the electric field and penetration depth (PD) for the same sample. In this study, the normal and infected blood samples are successfully examined for the performance parameters for the plasma, platelets and hemoglobin. [ABSTRACT FROM AUTHOR]

Background and Objectives: Clearances and the area under the plasma concentration–time curve extrapolated to infinity (AUC0–∞) of intravenous (IV) and oral midazolam and alfentanil are probes for hepatic and first-pass cytochrome P450 3A (CYP3A) activity, drug interactions, and phenotyping. Single-time plasma concentrations are also used as a proxy for clearance and AUC0–∞. Pupil diameter change is a noninvasive surrogate for plasma alfentanil. An ideal probe should have minimal intrasubject (interday) variability. Despite their widespread use, the intrasubject variability of CYP3A probes is not well characterized. This investigation determined the intrasubject (interday) variability of midazolam and alfentanil metrics of hepatic and first-pass CYP3A. Methods: Twelve volunteers were studied in a four-period protocol, with each period identical and separated by approximately 2 weeks. In each period, participants received 1 mg IV midazolam then 15 μg/kg IV alfentanil 1 h later. The next day, they received 3 mg oral midazolam then 60 μg/kg oral alfentanil. Plasma drug concentrations were determined by liquid chromatography-mass spectrometry (LCMS). Dark-adapted pupil diameters were measured coincident with blood sampling. Plasma concentrations and pupil effects (miosis) were analyzed using noncompartmental methods. The results were the coefficient of variation (%CV, mean ± SD) across four sessions in 12 participants. Results: For IV midazolam: AUC0–∞, clearance, and 5 h concentration, the %CVs were 12 ± 3, 12 ± 3, and 18 ± 8. For IV alfentanil AUC0–∞, clearance, 2 h concentration, and area under the effect curve from time zero to infinity (AUEC0–∞), the %CVs were 16 ± 5, 15 ± 4, 22 ± 7, and 50 ± 28. For oral midazolam AUC0–∞, clearance, and 5 h concentration, %CVs were 19 ± 5, 18 ± 4, and 28 ± 11. For oral alfentanil: AUC0–∞, clearance, 4 h concentration, and AUEC0–∞, %CVs were 20 ± 4, 21 ± 4, 42 ± 26, and 37 ± 14. Conclusions: Midazolam and alfentanil had comparable intrasubject variabilities of clearance and AUC0–∞. Single-time point metrics had greater intrasubject variability than AUC0–∞ and clearance. Miosis was a surrogate for alfentanil concentrations and provided real-time results, but intrasubject variability was greater than that of clearances and AUC0–∞. [ABSTRACT FROM AUTHOR]

Metabolomics plays a crucial role in understanding metabolic processes within biological systems. Using specific pulse sequences, NMR-based metabolomics detects small and macromolecular metabolites that are altered in blood samples. Here we proposed a method called spectral editing neural network, which can effectively edit and separate the spectral signals of small and macromolecules in 1H NMR spectra of serum and plasma based on the linewidth of the peaks. We applied the model to process the 1H NMR spectra of plasma and serum. The extracted small and macromolecular spectra were then compared with experimentally obtained relaxation-edited and diffusion-edited spectra. Correlation analysis demonstrated the quantitative capability of the model in the extracted small molecule signals from 1H NMR spectra. The principal component analysis showed that the spectra extracted by the model and those obtained by NMR spectral editing methods reveal similar group information, demonstrating the effectiveness of the model in signal extraction. 1H NMR-based metabolomics can detect small and macromolecular metabolites simultaneously from complex biological samples, however, signaling overlap remains a challenge for accurate molecular identification and quantification. Here, the authors develop a spectral editing neural network to effectively edit and separate the spectral signals of small and macromolecules in the 1H NMR spectra of serum and plasma based on the linewidth of the peaks. [ABSTRACT FROM AUTHOR]

Purpose: Functional PET (fPET) is a novel technique for studying dynamic changes in brain metabolism and neurotransmitter signaling. Accurate quantification of fPET relies on measuring the arterial input function (AIF), traditionally achieved through invasive arterial blood sampling. While non-invasive image-derived input functions (IDIF) offer an alternative, they suffer from limited spatial resolution and field of view. To overcome these issues, we developed and validated a scan protocol for brain fPET utilizing cardiac IDIF, aiming to mitigate known IDIF limitations. Methods: Twenty healthy individuals underwent fPET/MR scans using [18F]FDG or 6-[18F]FDOPA, utilizing bed motion shuttling to capture cardiac IDIF and brain task-induced changes. Arterial and venous blood sampling was used to validate IDIFs. Participants performed a monetary incentive delay task. IDIFs from various blood pools and composites estimated from a linear fit over all IDIF blood pools (3VOI) and further supplemented with venous blood samples (3VOIVB) were compared to the AIF. Quantitative task-specific images from both tracers were compared to assess the performance of each input function to the gold standard. Results: For both radiotracer cohorts, moderate to high agreement (r: 0.60–0.89) between IDIFs and AIF for both radiotracer cohorts was observed, with further improvement (r: 0.87–0.93) for composite IDIFs (3VOI and 3VOIVB). Both methods showed equivalent quantitative values and high agreement (r: 0.975–0.998) with AIF-derived measurements. Conclusion: Our proposed protocol enables accurate non-invasive estimation of the input function with full quantification of task-specific changes, addressing the limitations of IDIF for brain imaging by sampling larger blood pools over the thorax. These advancements increase applicability to any PET scanner and clinical research setting by reducing experimental complexity and increasing patient comfort. [ABSTRACT FROM AUTHOR]

This study was performed to analyze fingertip capillary blood sampling in pediatric patients using microcapillary blood collection tubes and microhematocrit tubes and to compare the blood cell analysis results obtained via these two blood collection methods. Finger capillary blood was collected from 110 outpatients using microcapillary blood collection tubes and microhematocrit tubes and complete blood count analysis was performed with a Sysmex XS-900i hematology analyzer and manual microscopy for blood cell morphology. Paired data was evaluated for agreement and bias using the microhematocrit samples as the reference group and the samples from the microcapillary blood collection tubes as the observation group. The two blood collection methods demonstrated good agreement for measuring red blood cell (RBC) parameters (i.e., RBC, Hb, Hct, MCV, MCH and MCHC), wherein the relative bias was > allowable total error (TEa) in 0.91%, 1.82%, 11.82%, 1.82%, 0.91% and 8.18% of the parameter measures, respectively. According to industry requirements, the proportion of samples meeting the acceptable bias level should be > 80%. Additionally, the estimated biases at each medical decision level were within clinically acceptable levels for RBC, Hb, Hct, and MCV. However, the proportion of WBC and PLT counts with relative bias > TEa was 25.45% and 35.45%, respectively. Furthermore, the relative bias of the WBC count at the medical decision level of 0.5 × 109/L and that of the PLT counts at the medical decision levels of 10 × 109/L and 50 × 109/L were clinically significant. Bland–Altman analysis further showed a mean bias of 0.66 × 109/L (95% LoA, − 0.79 to 2.11) for the WBC count and 39 × 109/L (95% LoA, − 46 to 124) for the PLT count from the blood samples collected in the microcapillary blood collection tubes compared with the counts of those collected in the microhematocrit tubes. Neutrophil, monocyte, lymphocyte, eosinophil, and PLT counts increased significantly in the microcapillary blood collection tubes compared with those in the microhematocrit tubes, along with an elevated number of instrument false alarms (P < 0.05). The two capillary blood collection devices exhibit performance differences. Therefore, clinicians should pay attention to the variation in results caused by different blood collection methods. [ABSTRACT FROM AUTHOR]

Purpose: Functional positron emission tomography (fPET) with [18F]FDG allows quantification of stimulation-induced changes in glucose metabolism independent of neurovascular coupling. However, the gold standard for quantification requires invasive arterial blood sampling, limiting its widespread use. Here, we introduce a novel fPET method without the need for an input function. Methods: We validated the approach using two datasets (DS). For DS1, 52 volunteers (23.2 ± 3.3 years, 24 females) performed Tetris® during a [18F]FDG fPET scan (bolus + constant infusion). For DS2, 18 participants (24.2 ± 4.3 years, 8 females) performed an eyes-open/finger tapping task (constant infusion). Task-specific changes in metabolism were assessed with the general linear model (GLM) and cerebral metabolic rate of glucose (CMRGlu) was quantified with the Patlak plot as reference. We then estimated simplified outcome parameters, including GLM beta values and percent signal change (%SC), and compared them, region and whole-brain-wise. Results: We observed higher agreement with the reference for DS1 than DS2. Both DS resulted in strong correlations between regional task-specific beta estimates and CMRGlu (r = 0.763...0.912). %SC of beta values exhibited strong agreement with %SC of CMRGlu (r = 0.909...0.999). Average activation maps showed a high spatial similarity between CMRGlu and beta estimates (Dice = 0.870...0.979) as well as %SC (Dice = 0.932...0.997), respectively. Conclusion: The non-invasive method reliably estimates task-specific changes in glucose metabolism without blood sampling. This streamlines fPET, albeit with the trade-off of being unable to quantify baseline metabolism. The simplification enhances its applicability in research and clinical settings. [ABSTRACT FROM AUTHOR]

Purpose: Despite the importance of self-monitoring blood glucose (SMBG) for management of diabetes mellitus (DM), frequent blood sampling is discouraged by bleeding risk due to dual-antiplatelet agent therapy (DAPT) or thrombocytopenia. Methods: We compared the bleeding time (BT) of sampling by using a laser-lancing-device (LMT-1000) and a conventional lancet in patients with DM and thrombocytopenia or patients undergoing DAPT. BT was measured using the Duke method, and pain and satisfaction scores were assessed using numeric rating scale (NRS) and visual analog scale (VAS). The consistency in the values of glucose and glycated-hemoglobin (HbA1c) sampled using the LMT-1000 or lancet were compared. Results: The BT of sampling with the LMT-1000 was shorter than that with the lancet in patients with thrombocytopenia (60s vs. 85s, P = 0.024). The NRS was lower and the VAS was higher in laser-applied-sampling than lancet-applied sampling in the DAPT-user group (NRS: 1 vs. 2, P = 0.010; VAS: 7 vs. 6, P = 0.003), whereas the group with thrombocytopenia only showed improvement in the VAS score (8 vs. 7, P = 0.049). Glucose and HbA1c sampled by the LMT-1000 and lancet were significantly correlated in both the DAPT-user and the thrombocytopenia groups. Conclusion: The LMT-1000 can promote SMBG by shortening BT in subject with thrombocytopenia and by increasing satisfaction score, as well as by showing reliable glucose and HbA1c value. [ABSTRACT FROM AUTHOR]

An optical biosensor designed using a Nanocomposite/Defect/Nanocomposite multilayer 1D photonic crystal is proposed for malaria diagnosis. The defect layer represents blood samples corresponding to various stages of malaria. Employing the Transmission Matrix Method (TMM), we analyse the impact of two kind of nanocomposite (NC) layers: silver-doped TiO2 and silver-doped SiO2. Comparative analyses involving varying thickness and fill factor of NC layers indicate increased sensitivity with higher fill factors and thickness, albeit with a decrease in transmission. Further, we explore the influence of incident angle (TM & TE mode) on sensing performance, revealing enhanced sensitivity at higher angles. The maximum sensitivity peaks are reported to be 1074 nm/RIU and 1064 nm/RIU for the mentioned NC layer cases. This biosensor promises enhanced sensitivity and potential for advanced malaria diagnostics. [ABSTRACT FROM AUTHOR]

Objective: To compare the diagnostic efficacy of multiplex polymerase chain reaction (PCR), Mycobacterium leprae-specific repetitive element (RLEP) PCR and loop-mediated isothermal amplification (LAMP) PCR in the diagnosis of pediatric leprosy as an alternative to slit-skin smear (SSS) examination. Methods: A cross-sectional study was performed on 26 children aged 0–18 years with characteristic skin lesions of leprosy. SSS examination for acid fast bacilli (AFB) was performed for all children. Additionally, urine, stool and blood samples were tested by three PCR techniques - multiplex, RLEP and LAMP. The results of these tests were compared with each other and with results of SSS examination for acid fast bacilli (AFB) using appropriate statistical tests. Results: Out of 26 patients studied, SSS examination was positive for AFB in 7 cases (26.9%). In blood samples, the positivity of multiplex PCR, RLEP PCR and LAMP PCR was 84.6%, 80.8%, and 80.8%, respectively. Multiplex PCR in blood samples was positive in 100% (n = 7) of SSS positive cases and 84.2% (16 out of 19) of the SSS negative cases (P < 0.001). The positivity of all PCR methods in urine and stool samples was significantly lesser than in blood. Conclusion: Multiplex PCR in blood sample is a superior diagnostic tool for pediatric leprosy compared to RLEP PCR and LAMP PCR as well as SSS examination. [ABSTRACT FROM AUTHOR]

One significant constraint in the advancement of biosensors is the signal-to-noise ratio, which is adversely affected by the presence of interfering factors such as blood in the sample matrix. In the present investigation, a specific aptamer binding was chosen for its affinity, while exhibiting no binding affinity towards non-target bacterial cells. This selective binding property was leveraged to facilitate the production of magnetic microparticles decorated with aptamers. A novel assay was developed to effectively isolate S. pneumoniae from PBS or directly from blood samples using an aptamer with an affinity constant of 72.8 nM. The capture experiments demonstrated efficiencies up to 87% and 66% are achievable for isolating spiked S. pneumoniae in 1 mL PBS and blood samples, respectively. [ABSTRACT FROM AUTHOR]

A ternary hierarchical hybrid Ni@CoxSy/poly(3,4-ethylenedioxythiophene)-reduced graphene oxide (Ni@CoxSy/PEDOT-rGO) is rationally designed and in situ facilely synthesized as electrocatalyst to construct a binder-free sensing platform for non-enzymatic glucose monitoring through traditional electrodeposition procedure. The as-prepared Ni@CoxSy/PEDOT-rGO presents unique hierarchical structure and multiple valence states as well as strong and robust adhesion between Ni@CoxSy/PEDOT-rGO and GCE. Profiting from the aforementioned merits, the sensing platform constructed under optimal conditions achieved a wide detection range (0.2 μM ~ 2.0 mM) with high sensitivity (1546.32 μA cm–2 mM–1), a rapid response time (5 s), an ultralow detection limit (0.094 μM), superior anti-interference performance, excellent reproducibility and considerable stability. Furthermore, the sensor demonstrates an acceptable accuracy and appreciable recoveries ranging from 90.0 to 102.0% with less than 3.98% RSD in human blood serum samples, indicating the prospect of the sensor for the real samples analysis. It will provide a strategy to rationally design and fabricate ternary hierarchical hybrid as nanozyme for glucose assay. [ABSTRACT FROM AUTHOR]

The human mannose-binding lectin (MBL) gene encodes a polymorphic protein that plays a crucial role in the innate immune response. Human MBL deficiency is associated with immunodeficiencies, and its variants have been linked to autoimmune and infectious diseases. Despite this significance, gene studies concerning MBL sequencing are uncommon in Malaysia. Therefore, we aimed to preliminary described the human MBL sequencing dataset based on the Kelantan population. Blood samples were collected from 30 unrelated individuals and underwent DNA extraction, genotyping, and sequencing. The sequencing data generated 886 bp, which were deposited in GenBank (ON619541-ON619546). Allelic variants were identified and translated into six MBL haplotypes: HYPA, HYPB, LYPB, LXPB, HXPA, and LXPA. An evolutionary tree was constructed using the haplotype sequences. These findings contribute to the expansion of MBL information within the country, providing a valuable baseline for future research exploring the association between the gene and targeted diseases. [ABSTRACT FROM AUTHOR]

Background: Peptide receptor radionuclide therapy with 177Lu-DOTATATE is a recognized option for treating neuroendocrine tumors and has few toxicities, except for the kidneys and bone marrow. The bone marrow dose is generally derived from a SPECT/CT image-based method with four timepoints or from a blood-based method with up to 9 timepoints, but there is still no reference method. This retrospective single-center study on the same cohort of patients compared the calculated bone marrow dose administered with both methods using mono, bi- or tri-exponential models. For the image-based method, the dose was estimated using Planetdose© software. Pearson correlation coefficients were calculated. We also studied the impact of late timepoints for both methods. Results: The bone marrow dose was calculated for 131 treatments with the blood-based method and for 17 with the image-based method. In the former, the median absorbed dose was 15.3, 20.5 and 28.3 mGy/GBq with the mono-, bi- and tri-exponential model, respectively. With the image-based method, the median absorbed dose was 63.9, 41.9 and 60.8 with the mono-, bi- and tri-exponential model, respectively. Blood samples after 24h post-injection did not evidence any change in the absorbed bone marrow dose with the bi-exponential model. On the contrary, the 6-day post-injection timepoint was more informative with the image-based model. Conclusion: This study confirms that the estimated bone marrow dose is significantly lower with the blood-based method than with the image-based method. The blood-based method with a bi-exponential model proved particularly useful, without the need for blood samples after 24h post-injection. Nevertheless, this blood-based method is based on an assumption that needs to be more validated. The important difference between the two methods does not allow to determine the optimal one to estimate the true absorbed dose and further studies are necessary to compare with biological effects. [ABSTRACT FROM AUTHOR]

The pharmacokinetic properties of dihydroquercetin (DHQ) were studied after single and repeated (for 3 days) administration to rats in the form of a starch suspension at a dose of 25 mg/kg. Blood samples were collected using a permanent catheter in the jugular vein in 2, 5, 10, 20, and 30 min and in 1, 2, 4, and 6 h after administration. Before the repeated administration (5 min), blood sample was collected to assess the concentration of DHQ at the zero time point. Quantitative analysis was carried out by HPLC-tandem mass spectrometry. DHQ was very quickly absorbed by the gastrointestinal tract and quickly eliminated from the body. Repeated administration of DHQ did not lead to its accumulation in the body but had an effect on the enzymatic system with a subsequent increase in DHQ exposure (accumulation factor >1 by AUC after repeated administration). [ABSTRACT FROM AUTHOR]

This survey sought to molecularly detect Coxiella burnetii in Argasidae and Ixodidae ticks attached to small ruminants in the region of West Azerbaijan (Northwest of Iran) and blood samples collected from the same animals. 451 tick samples and 927 blood samples were obtained from sheep (n = 536) and goats (n = 391) and tested by nested PCR for detection of C. burnetii insertion sequence IS1111 or icd gene sequence. The collected ticks were morphologically classified as Rhipicephalus sanguineus, Rhipicephalus turanicus, Hyalomma asiaticum, Hyalomma anatolicum, or Argas reflexus. 14% of ticks (65 in total 43 for IS1111 and 22 for icd gene) tested positive for C. burnetii, none of which were from the Argas genus. Among the 927 blood samples, 218 (23.5%) tested positive for C. burnetii. The positive result from analysis targeting the genes IS1111 and icd were 131 and 87 respectively. As Q fever is a tickborne zoonosis and endemic to Iran, such information is critical for creating effective, coordinated, and strategic tick and pathogen control programs to prevent disease outbreak in domestic animals and humans. [ABSTRACT FROM AUTHOR]

Uric acid (UA) is an important biomarker, as a high concentration in blood can lead to gout and further renal syndrome. Although several point-of-care testing (POCT) devices have been reported to detect UA, there are some limitations such as the requirement for uricase and the complicated pretreatment of serum/plasma samples, which restricts their use at home or in undeveloped areas. In this work, we developed an approach by applying Zn2+ to precipitate proteins and cells in whole blood to avoid interference with the chromogenic reaction. We used carboxymethylcellulose (CMC) to immobilize tetramethylbenzidine (TMB) on a nitrocellulose membrane for colorimetric detection. Using the oxidization properties of H2O2, which turns TMB into oxidized tetramethylbenzidine (TMBox) in the presence of catalyst gold nanoparticles (AuNPs), we successfully constructed an enzyme-free paper-based POCT device using the reduction reaction of UA and TMBox for simple, speedy, and cheap colorimetric detection of UA, achieving a detection time of 8 min, a linear range of 0–150 μg/mL, and an LOD of 25.79 μg/mL. The UA concentration in whole blood samples was further measured and correlated well with the clinical value (R2 = 0.8212). Thus, the proposed assay has the potential for POCT diagnosis, monitoring, and prognosis of diseases related to UA. By applying Zn2+ reagent to precipitate proteins and cells in whole blood and the reduction reaction of UA, an enzyme-free paper-based POCT assay was established. [ABSTRACT FROM AUTHOR]

Background: We designed and synthesized a novel bisphosphonate radiopharmaceutical (68 Ga- or 177Lu-labeled DOTA-ibandronate [68 Ga/177Lu-DOTA-IBA]) for the targeted diagnosis and treatment of bone metastases. The biodistribution and internal dosimetry of a single therapeutic dose of 177Lu-DOTA-IBA were evaluated using a series of single-photon emission computerized tomography (SPECT) images and blood samples. Five patients with multiple bone metastases were included in this prospective study. After receiving 1110 MBq 177Lu-DOTA-IBA, patients underwent whole-body planar, SPECT/CT imaging and venous blood sampling over 7 days. Dosimetric evaluation was performed for the main organs and tumor lesions. Safety was assessed using blood biomarkers. Results: 177Lu-DOTA-IBA showed fast uptake, high retention in bone lesions, and rapid clearance from the bloodstream in all patients. In this cohort, the average absorbed doses (ADs) in the bone tumor lesions, kidneys, liver, spleen, red marrow, bladder-wall, and osteogenic cells were 5.740, 0.114, 0.095, 0.121, 0.095, and 0.333 Gy/GBq, respectively. Although no patient reached the predetermined dose thresholds, the red marrow will be the dose-limiting organ. There were no adverse reactions recorded after the administration of 1110 MBq 177Lu-DOTA-IBA. Conclusion: Dosimetric results show that the ADs for critical organs and total body are within the safety limit and with high bone retention. It is a promising radiopharmaceutical alternative for the targeted treatment of bone metastases, controlling its progression, and improving the survival and quality of life of patients with advanced bone metastasis. [ABSTRACT FROM AUTHOR]

Background: Accurate image-derived input function (IDIF) from highly sensitive large axial field of view (LAFOV) PET/CT scanners could avoid the need of invasive blood sampling for kinetic modelling. The aim is to validate the use of IDIF for two kinds of tracers, 3 different IDIF locations and 9 different reconstruction settings. Methods: Eight [18F]FDG and 10 [18F]DPA-714 scans were acquired respectively during 70 and 60 min on the Vision Quadra PET/CT system. PET images were reconstructed using various reconstruction settings. IDIFs were taken from ascending aorta (AA), descending aorta (DA), and left ventricular cavity (LV). The calibration factor (CF) extracted from the comparison between the IDIFs and the manual blood samples as reference was used for IDIFs accuracy and precision assessment. To illustrate the effect of various calibrated-IDIFs on Patlak linearization for [18F]FDG and Logan linearization for [18F]DPA-714, the same target time-activity curves were applied for each calibrated-IDIF. Results: For [18F]FDG, the accuracy and precision of the IDIFs were high (mean CF ≥ 0.82, SD ≤ 0.06). Compared to the striatum influx (Ki) extracted using calibrated AA IDIF with the updated European Association of Nuclear Medicine Research Ltd. standard reconstruction (EARL2), Ki mean differences were < 2% using the other calibrated IDIFs. For [18F]DPA714, high accuracy of the IDIFs was observed (mean CF ≥ 0.86) except using absolute scatter correction, DA and LV (respectively mean CF = 0.68, 0.47 and 0.44). However, the precision of the AA IDIFs was low (SD ≥ 0.10). Compared to the distribution volume (VT) in a frontal region obtained using calibrated continuous arterial sampler input function as reference, VT mean differences were small using calibrated AA IDIFs (for example VT mean difference = -5.3% using EARL2), but higher using calibrated DA and LV IDIFs (respectively + 12.5% and + 19.1%). Conclusions: For [18F]FDG, IDIF do not need calibration against manual blood samples. For [18F]DPA-714, AA IDIF can replace continuous arterial sampling for simplified kinetic quantification but only with calibration against arterial blood samples. The accuracy and precision of IDIF from LAFOV PET/CT system depend on tracer, reconstruction settings and IDIF VOI locations, warranting careful optimization. [ABSTRACT FROM AUTHOR]

This study presents a biosensor working at a frequency of 3.5 GHz, which is designed as a square ring metamaterial resonator. This study aimed to evaluate the impact of blood amount on the metamaterial-based resonator sensor's sensitivity. The structure was constructed using Rogers-RT5880 material, with an overall area of 85.71 mm × 85.71 mm2. The simulation of the design involved modelling the blood samples using Debye 1st-order equations. The empirical results observed a noticeable shift towards a lower frequency range in the response and changes in the magnitude, corresponding to an increase in the blood sample's glucose concentration and thickness. Following this, the experiment was designed to corroborate the simulated results. The sensor achieved the highest sensitivity of 0.23 dB per 100 mg/dl change in glucose level when the thickness of blood was 0.1 mm. It was concluded from the results that the increase in the volume of blood increases the sensor's sensitivity. However, a trade-off mark is necessary in which an optimum sensitivity is achieved with blood volume as minimum as possible so that a noninvasive biosensor can be designed. [ABSTRACT FROM AUTHOR]

Breeding seabirds must balance the energetic demands of feeding themselves and their offspring while coping with the constraints imposed by central-place foraging. As such, foraging strategies and parental care patterns are usually linked. Here, the foraging behavior of the Red-billed Tropicbird (Phaethon aethereus; n = 161) of Peña Blanca Islet, Mexico (19° 06ʹ 11ʺ N, 104° 29ʹ 12ʺ W) during the incubation and chick-rearing (≤ 4 weeks of age) stages was characterized with the aid of GPS loggers. Blood samples from adults and chicks were collected to determine δ15N and δ13C, and parental presence at the nest, meal size, and parent-chick feeding events were recorded. During incubation, parents made long trips offshore to areas far from the colony; however, immediately after their chicks hatched, the parents switched to a bimodal foraging strategy by undertaking both short and long foraging trips. The δ15N values indicated that trophic differences were present between parents and their offspring, with chicks being fed prey enriched in 15N. Parental presence at the nest was greater during early chick-rearing, which was associated with a higher provisioning rate. Parents adopted a strategy in which the parent on nest duty only made short foraging trips to provide for its offspring without leaving it unattended for long periods, while its mate undertook long trips to feed itself. After the early chick-rearing period, the parents gradually reduced the time spent at the nest and increased the time spent foraging, compensating with larger meal sizes for their offspring. [ABSTRACT FROM AUTHOR]

Introduction: Proactive drug facilitated crime (DFC) is the administration of psychoactive substances (PAS) for criminal purposes without the victim's knowledge or by force. In Paris, France, patients who report suspected proactive DFC to the police are examined at the Department of Forensic Medicine (DFM) of the Hôtel-Dieu Hospital. Preventively blood and urine samples are collected but not systematically analyzed by the judicial authority. We aimed to assess the proportion of probable proactive DFC in patients examined at the Hôtel-Dieu DFM following a police report for suspected proactive DFC. Method: Blood and urine samples were collected from 100 patients. Toxicological analyses were performed by the toxicology laboratory of the Lariboisière Hospital. The results were correlated with the clinical data collected at the initial and follow-up consultations. Results: At least one PAS was detected in 86% of the cases (voluntary or involuntary intake). After correlation with clinical data, 32% of the cases were classified as probable proactive DFC. In these cases, 49% of the substances identified were illicit substances (amphetamines, MDMA, etc.); 16% were benzodiazepines and related substances; 16% were antihistamines and sedatives; 14% were opioids; and 5% were antidepressants and anti-epileptics. In 90% of the cases, patients reported a voluntary ethanol consumption in the hours prior to the suspected proactive DFC. Conclusion: Toxicological analyses revealed a high proportion of both probable proactive DFC and probable opportunistic DFC. Our results indicate the need to perform systematical toxicological analysis in cases of suspected DFC. [ABSTRACT FROM AUTHOR]

In this study, a novel adsorbent was prepared by modification of graphite with deep eutectic solvent based on camphor–thymol (by the mole ratio of 1:1) and was utilized as a separation phase for pipette tip micro-solid phase extraction of mitoxantrone from seawater, drug, urine and blood samples. After extraction, mitoxantrone content of samples was determined by spectrophotometry at 260 nm wavelength. Various variables which could affect the extraction, including pH, amount of extracting phase, volumes of sample and eluent, type of eluent, and number of the extraction/ejection cycles of solution and eluent, were evaluated and optimized by both one-variable-at-a-time and response surface methodology methods. Observations indicated that the highest extraction achieved when 200 mg of the adsorbent was employed for 100 µL of sample solution with 7 extraction cycles at pH 7.0. Analyte was desorbed from the adsorbent by 200 µL of methanol (as eluent) after 3 ejection cycles. The linear dynamic range of the technique was between 1 and 1000 µg L−1, and the limit of detection and quantification were 0.2 µg L−1 and 0.7 µg L−1, respectively. Finally, the proposed extraction was successfully employed for the determination of mitoxantrone in various real samples with complicated matrices. [ABSTRACT FROM AUTHOR]

Granzyme B, mostly expressed by cytotoxic T lymphocytes in the fight against cancer and infection, is known to induce cell death based on its active enzymatic activity as a serine protease. Recent studies showed cytotoxicity of a non-enzymatic granzyme B-like peptide (also referred to as granzyme B-associated peptide or GP1 in this report) in tumor cells and presence of binding targets for GP1R (i.e., GP1 conjugated with rhodamine fluorochrome) in tumor cells, bacteria, and circulating platelets/neutrophils of healthy hosts. But there were no data on "sick" hosts to help substantiate any potential GP1 based medical applications. Thus, we adopted similar GP1R binding protocols to further study binding of GP1 in different biological samples (including different blood samples of hosts in sickness and in health, cancer cell lines, and trigeminal ganglia culture of infected hosts treated with and without GP1) and determine if any binding patterns might have any associations with different health conditions. The overall preliminary results appear to show certain GP1R + binding patterns in certain blood components (especially neutrophils) have potential correlations with certain health conditions of hosts at sampling times, indicating potential GP1R applications for diagnostic purposes. Findings of different GP1R binding patterns in different cancer cell lines, whole blood samples and trigeminal ganglia culture of experimental mice infected with HSV-1 virus (might cause neuropathy) within a week post-infection, and blood samples of GP1-treated mouse survivors on day 21 post-infection provided preliminary evidence of potential GP1-led tumor cell-specific cell death and treatment efficacy for greater survival. [ABSTRACT FROM AUTHOR]

Personalised drug dosing through therapeutic drug monitoring (TDM) is important to maximise efficacy and to minimise toxicity. Hurdles preventing broad implementation of TDM in routine care include the need of sophisticated equipment and highly trained staff, high costs and lack of timely results. Salivary TDM is a non-invasive, patient-friendly alternative to blood sampling, which has the potential to overcome barriers with traditional TDM. A mobile UV spectrophotometer may provide a simple solution for analysing drug concentrations in saliva samples. Salivary TDM utilising point-of-care tests can support personalised dosing in various settings including low-resource as well as remote settings. In this opinion paper, we describe how hurdles of implementing traditional TDM may be mitigated by salivary TDM with new strategies for patient-friendly point-of-care testing. [ABSTRACT FROM AUTHOR]

Circulating endothelial cells (CEC) are arising as biomarkers for vascular diseases. However, whether they can be utilized as markers of endothelial cell (EC) senescence in vivo remains unknown. Here, we present a protocol to isolate circulating endothelial cells for a characterization of their senescent signature. Further, we characterize different models of EC senescence induction in vitro and show similar patterns of senescence being upregulated in CECs of aged patients as compared to young volunteers. Replication-(ageing), etoposide-(DNA damage) and angiotensin II-(ROS) induced senescence models showed the expected cell morphology and proliferation-reduction effects. Expression of senescence-associated secretory phenotype markers was specifically upregulated in replication-induced EC senescence. All models showed reduced telomere lengths and induction of the INK4a/ARF locus. Additional p14ARF-p21 pathway activation was observed in replication- and etoposide-induced EC senescence. Next, we established a combined magnetic activated- and fluorescence activated cell sorting (MACS-FACS) based protocol for CEC isolation. Interestingly, CECs isolated from aged volunteers showed similar senescence marker patterns as replication- and etoposide-induced senescence models. Here, we provide first proof of senescence in human blood derived circulating endothelial cells. These results hint towards an exciting future of using CECs as mirror cells for in vivo endothelial cell senescence, of particular interest in the context of endothelial dysfunction and cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background: PET scans using zirconium-89 labelled monoclonal antibodies (89Zr-mAbs), known as 89Zr-immuno-PET, are made to measure uptake in tumour and organ tissue. Uptake is related to the supply of 89Zr-mAbs in the blood. Measuring activity concentrations in blood, however, requires invasive blood sampling. This study aims to identify the best delineation strategy to obtain the image-derived blood concentration (IDBC) from 89Zr-immuno-PET scans. Methods: PET imaging and blood sampling of two 89Zr-mAbs were included, 89Zr-cetuximab and 89Zr-durvalumab. For seven patients receiving 89Zr-cetuximab, PET scans on 1–2 h, 2 and 6 days post-injection (p.i.) were analysed. Five patients received three injections of 89Zr-durvalumab. The scanning protocol for the first two injections consisted of PET scanning on 2, 5 and 7 days p.i. and for the third injection only on 7 days p.i. Blood samples were drawn with every PET scan and the sample-derived blood concentration (SDBC) was used as gold standard for the IDBC. According to an in-house developed standard operating procedure, the aortic arch, ascending aorta, descending aorta and left ventricle were delineated. Bland–Altman analyses were performed to assess the bias (mean difference) and variability (1.96 times the standard deviation of the differences) between IDBC and SDBC. Results: Overall, the activity concentration obtained from the IDBC was lower than from the SDBC. When comparing IDBC with SDBC, variability was smallest for the ascending aorta (20.3% and 17.0% for 89Zr-cetuximab and 89Zr-durvalumab, respectively). Variability for the other regions ranged between 17.9 and 30.8%. Bias for the ascending aorta was − 10.9% and − 11.4% for 89Zr-cetuximab and 89Zr-durvalumab, respectively. Conclusions: Image-derived blood concentrations should be obtained from delineating the ascending aorta in 89Zr-immuno-PET scans, as this results in the lowest variability with respect to sample-derived blood concentrations. [ABSTRACT FROM AUTHOR]

Introduction: There is no clear correlation between abnormal umbilical cord blood gas studies (UCGS) and adverse neonatal outcome in low-risk deliveries. We investigated the need for its routine use in low-risk deliveries. Methods: We retrospectively compared maternal, neonatal, and obstetrical characteristics among low-risk deliveries (2014–2022) between "normal" and "abnormal" pH groups: A:normal pH ≥ 7.15; abnormal pH < 7.15; B: normal pH ≥ 7.15 and base excess (BE) > − 12 mmol/L; abnormal pH < 7.15 and BE ≤ We retrospectively compared 12 mmol/L; C: normal pH ≥ 7.1; abnormal pH < 7.1; D: normal pH > 7.1 and BE > − 12 mmol/L; abnormal pH < 7.1 and BE ≤ − 12 mmol/L. Results: Of 14,338 deliveries, the rates of UCGS were: A—0.3% (n = 43); B—0.07% (n = 10); C—0.11% (n = 17); D—0.03% (n = 4). The primary outcome, composite adverse neonatal outcome (CANO) occurred in 178 neonates with normal UCGS (1.2%) and in only one case with UCGS (2.6%). The sensitivity and specificity of UCGS as a predictor of CANO were high (99.7–99.9%) and low (0.56–0.59%), respectively. Conclusion: UCGS were an uncommon finding in low-risk deliveries and its association with CANO was not clinically relevant. Consequently, its routine use should be considered. [ABSTRACT FROM AUTHOR]

Catestatin (CST) is a pleiotropic peptide with cardioprotective and metabolic effects. CST is involved in the pathogenesis of both arterial hypertension (AH) and type 2 diabetes mellitus (T2DM), which are the risk factors of cardiovascular diseases. In this study, we aimed to investigate the plasma CST levels in hypertensive patients, especially with T2DM, as well as compare those with healthy volunteers, and explore the relationship between CST levels and clinical, anthropometric and laboratory parameters. 106 Hypertensive patients, 55 of which had comorbidity T2DM, and 30 healthy volunteers were enrolled in the study. All subjects underwent clinical examination, including vital signs and anthropometric data assessment, medical history interview, and blood sample collection. Plasma CST levels were measured by an enzyme-linked immunosorbent assay (ELISA), using a commercial diagnostic kit. The plasma CST levels were significantly lower in hypertensive patients (N = 106) compared with healthy subjects (N = 30) (5.02 ± 1.09 vs. 6.64 ± 0.72; p < 0.001). Furthermore, hypertensive patients with T2DM (N = 55) have significantly reduced CST levels in comparison with those without T2DM (N = 51) (4.47 ± 1.16 vs. 5.61 ± 0.61; p < 0.001). CST significantly correlated with anthropometric characteristics, in particular, weight (r = − 0.344; p < 0.001), BMI (r = − 0.42; p < 0.001), neck (r = − 0.358; p < 0.001), waist (r = − 0.487; p < 0.001), hip (r = − 0.312; p < 0.001), wrist circumferences (r = − 0.264; p = 0.002), and waist-to-hip ratio (r = − 0.395; p < 0.001). Due to its antihypertensive effect, CST has significant associations with systolic BP (r = − 0.475; p < 0.001) and duration of AH (r = − 0.26; p = 0.007). CST also has an inverse relationship with insulin (r = − 0.382; p < 0.001), glucose (r = − 0.45; p < 0.001), index HOMA-IR (r = − 0.481; p < 0.001) and HbA1c (r = − 0.525; p < 0.001), that indicate its involvement in T2DM development. Besides, CST has significant correlations with uric acid levels (r = − 0.412; p < 0.001) as well as lipid parameters, especially HDL-C (r = 0.480; p < 0.001), VLDL-C (r = − 0.238; p = 0.005), TG (r = − 0.4; p < 0.001), non-HDL-C/HDL-C (r = − 0.499; p < 0.001). Multiple linear regression analysis indicated BMI (β = − 0.22; p = 0.007), AH duration (β = − 0.25; p = 0.008), HbA1c (β = − 0.43; p = 0.019) and HDL-C levels (β = 0.27; p = 0.001) as independent predictors of CST levels. The hypertensive patients have significantly decreased CST levels that are even more reduced in the presence of comorbid T2DM. The established correlations with anthropometric and laboratory parameters indicate not only antihypertensive but also metabolic effects of CST. Our results suggest the probable role of CST in the pathophysiology of cardiometabolic diseases and the development of cardiovascular complications. [ABSTRACT FROM AUTHOR]

The OXA-48-producing hypervirulent Klebsiella pneumoniae (hvKP) strains were rarely reported. In this study, we characterized three carbapenem-resistant hvKP strains (KP2185, NCRE61, and KP2683-1) isolated from renal abscess, scrotal abscess, and blood samples in a Taiwan hospital. The three strains belonged to two different clones: ST23 K1 (KP2683-1) and ST11 KL64 (KP2185 and NCRE61). KP2683-1 exhibited the highest virulence in an in vivo model. Whole-genome sequencing analysis showed that KP2185 and NCRE61 acquired IncFIB type plasmids containing a set of virulence genes (iroBCDN, iucABCD, rmpA, rmpA2, and iutA), while KP2683-1 acquired an IncL type plasmid harboring blaOXA-48. [ABSTRACT FROM AUTHOR]

Dispersive solid phase extraction/back–extraction of Ibuprofen using multi-walled carbon nanotubes as sorbent was studied. The effects of some factors on Ibuprofen extraction were investigated. pH of IP solution and temperature were more effective on IP adsorption than other investigated parameters. The obtained preconcentration factor was 11.43. A linear range of 10.31 – 206.28 mg/L (R2 = 0.997) was obtained for the HPLC method. The detection limit and relative standard deviation were 4.93 mg/l and 2.27%, respectively. Extraction and HPLC/UV determination of Ibuprofen in the human blood serum samples was carried out efficiently using the suggested procedure. The obtained results showed satisfactory selectivity and efficiency for the extraction of Ibuprofen molecules from the matrix of the Human blood serum samples. The suggested method is simple, efficient, fast, without usage of organic solvents, and low cost for separation, extraction, and determination of Ibuprofen molecules. [ABSTRACT FROM AUTHOR]

Recent studies have suggested benefits for time-dependent dialysate bicarbonate concentrations (Dbic) during hemodialysis (HD). In this clinical trial, we compared for the first time in the same HD patients the effects of time-dependent changes with constant Dbic on acid–base and uremic solute kinetics. Blood acid–base and uremic solute concentration were measured in twenty chronic HD patients during 4-h treatments with A) constant Dbic of 35 mmol/L; B) Dbic of 35 mmol/L then 30 mmol/L; and C) Dbic of 30 mmol/L then 35 mmol/L (change of Dbic after two hours during Treatments B and C). Arterial blood samples were obtained predialysis, every hour during HD and one hour after HD, during second and third treatments of the week with each Dbic concentration profile. Blood bicarbonate concentration (blood [HCO3]) during Treatment C was lower only during the first three HD hours than in Treatment A. Overall blood [HCO3] was reduced during Treatment B in comparison to Treatment A at each time points. We conclude that a single change Dbic in the middle of HD can alter the rate of change in blood [HCO3] and pH during HD; time-dependent Dbic had no influence on uremic solute kinetics. [ABSTRACT FROM AUTHOR]

In this paper, we present a human-based computation approach for the analysis of peripheral blood smear (PBS) images images in patients with Sickle Cell Disease (SCD). We used the Mechanical Turk microtask market to crowdsource the labeling of PBS images. We then use the expert-tagged erythrocytesIDB dataset to assess the accuracy and reliability of our proposal. Our results showed that when a robust consensus is achieved among the Mechanical Turk workers, probability of error is very low, based on comparison with expert analysis. This suggests that our proposed approach can be used to annotate datasets of PBS images, which can then be used to train automated methods for the diagnosis of SCD. In future work, we plan to explore the potential integration of our findings with outcomes obtained through automated methodologies. This could lead to the development of more accurate and reliable methods for the diagnosis of SCD. [ABSTRACT FROM AUTHOR]

Eutylone is a cathinone-derived synthetic amphetamine scheduled by the World Health Organization and European Monitoring Centre for Drugs and Drug Addiction since 2022 due to its growing consumption. We report here an eutylone intoxication involving a 38-year-old man and a 29-year-old woman in a chemsex context. A bag containing a white crystalline powder labelled as a research product was found in their vehicle. Nuclear magnetic resonance and liquid chromatography-high-resolution mass spectrometry (LC-HRMS) analyses identified the powder as eutylone and confirmed purity superior to 99%. LC-HRMS data analysis using molecular networking allowed to propose new eutylone metabolites in blood samples in a graphical manner. We described 16 phase I (e.g. hydroxylated or demethylated) and phase II metabolites (glucuroconjugates and sulfoconjugates). The same metabolites were found both in male and female blood samples. Toxicological analyses measured eutylone concentration in blood samples at 1374 ng/mL and 1536 ng/mL for the man and the woman, respectively. A keto-reduced metabolite (m/z 238.144) was synthesized to permit its quantification at 67 ng/mL and 54 ng/mL in male and female blood samples, respectively. Overall, the identification of these metabolites will increase the knowledge of potential drug consumption markers and allow to implement mass spectrometry databases to better monitor future drug abuse or consumption. [ABSTRACT FROM AUTHOR]

A new aptamer-based method has been developed for interferon-γ (IFN-γ) detection by utilizing interface reactivity-modulated fluorescent metal–organic frameworks (MOFs). Specifically, the binding of IFN-γ to its aptamer decreases the interface reactivity between the biotin-labeled aptamer and the streptavidin-functionalized magnetic beads by generating significant steric effects. As a result, several biotin-labeled aptamers escape from the enrichment of magnetic beads and remain in the supernatant, which subsequently undergo the terminal deoxynucleotidyl transferase-catalyzed polymerization elongation. Along with the elongation, pyrophosphate is continuously produced as the by-product, triggering the decomposition of fluorescent MOFs to generate a remarkable fluorescent response with the excitation/emission wavelength of 610 nm/685 nm. Experimental results show that the method enables the detection of IFN-γ in the range 0.06 fM to 6 pM with a detection limit of 0.057 fM. The method also displays high specificity and repeatability with an average relative standard deviation of 2.04%. Moreover, the method demonstrates satisfactory recoveries from 96.3 to 105.5% in serum samples and excellent utility in clinical blood samples. Therefore, this work may provide a valuable tool for IFN-γ detection and is expected to be of high potential in tuberculosis diagnosis in the future. [ABSTRACT FROM AUTHOR]

We evaluated modifications in the hemostatic balance of different concentrations of apixaban (APIX) in 25 healthy donors and 53 patients treated with aspirin (ASA, n = 21), ASA and clopidogrel (ASA + CLOPI, n = 11), or ASA and ticagrelor (ASA + TICA, n = 21). Blood samples from participants were spiked ex vivo with apixaban 0 (APIX0), 40 (APIX40), and 160 ng/mL (APIX160). We assessed the effects of APIX on (1) clot formation, by ROTEM thromboelastometry; (2) thrombin generation primed by platelets; and (3) platelet and fibrin interactions with a thrombogenic surface, in a microfluidic model with circulating blood. APIX caused dose-related prolongations of clotting time with minimal impact on other ROTEM parameters. Thrombin generation was significantly inhibited by APIX160, with ASA + TICA actions showing the strongest inhibition (p < 0.01 vs APIX0). Microfluidic studies showed that APIX160 was more potent at suppressing platelet and fibrin interactions (p < 0.001 vs. APIX0). APIX40 demonstrated a consistent antithrombotic action but with a favorable protective effect on the structural quality of fibrin. APIX potentiated the antithrombotic effects of current antiplatelet regimens. APIX at 40 ng/mL, enhanced the antithrombotic action of single or dual antiplatelet regimens but was more conservative for hemostasis than the 160 ng/mL concentration. [ABSTRACT FROM AUTHOR]

Inflammation plays an important role in Cardiovascular disease (CVD) pathogenesis as the main cause of mortality in hemodialysis (HD) patients. Despite the relevance of nutrition and dietary intakes for inflammation status, the role of dietary protein sources remains unclear. The aim of this study was to evaluate the association between the different types of dietary protein and pentraxin 3 (PTX3) levels in HD patients. In this multi-center cross-sectional study, 227 adult patients undergoing HD for a minimum 90 days were recruited. A validated 168-item food frequency questionnaire was used to assess dietary intakes. Also, 5 ml blood samples were collected from each patient to measure the concentration of serum PTX3. Overall, 227 patients, including 63 women and 164 men, with a mean age of 58 years, participated in this study. There was a greater intake of animal protein per kilogram dry weight among patients with higher levels of PTX3 (0.46 vs. 0.54 g/kg; P = 0.035). In contrast, consumption of total protein and plant protein per kilogram dry weight was not different across PTX3 levels. Moreover, the chance of increased PTX3 concentration was directly associated with a one-unit increase in animal protein intake per kilogram dry weight, after adjusting for confounders. We did not observe any association between one-unit increases in plant protein intake per kilogram dry weight and chance of increased PTX3. In conclusion, animal protein intake was directly associated with circulating PTX3. [ABSTRACT FROM AUTHOR]

The present study was focused on the current state of Dirofilaria species distribution in the territory of the Slovak Danubian Lowland, a region previously identified endemic for Dirofilaria repens. For the research, blood samples of 330 dogs tested positive for dirofilariosis using concentration tests or "rapid heartworm tests" were sent by private veterinary practitioners for further DNA analyses and species determination. The results revealed an unquestionable change in the pattern of Dirofilaria species distribution with Dirofilaria immitis, diagnosed as the agent of mono- and co-infections with D. repens, responsible for 60.00% of all cases. The results showed that in the course of the last 5 years, D. immitis has spread significantly in Slovakia and has become the dominant causal agent of dirofilariosis in the former endemic areas of D. repens distribution, which increases infection risk for both dogs and humans. [ABSTRACT FROM AUTHOR]

Coxiella burnetii can cause the zoonotic disease of Q fever, which has been observed in various species. Hyalomma aegyptium is a hard tick that undergoes its life cycle through three hosts. The spread of pathogens by Hyalomma aegyptium between different hosts can have significant epidemiological implications. The objective of this study was to detect the presence of C. burnetii in blood samples from turtles and H. aegyptium ticks attached to them in the northwest of Iran (Oshnavieh). A total of 500 engorged mature ticks and 100 blood samples were collected from 100 tortoises. Nested-PCR, using specific primers targeting the IS1111 and icd genes, was employed to diagnose C. burnetii. Out of the 100 tick pool samples, 10 were found to be infected with C. burnetii based on the IS1111 gene (10%; 95% CI, 5.5–17.4). The infection rate of C. burnetii in tick samples, as determined by the icd gene, was 6% (95% CI, 2.8–12.5). Furthermore, the infection rate of turtle blood with C. burnetii based on the IS1111 gene was 5% (95% CI, 2.2–11.2). The infection rate of the blood, as determined by the icd gene, was 3% (95% CI, 1–8.5). In conclusion, infected tortoises and H. aegyptium ticks carrying C. burnetii may play a role in transmitting this pathogenic agent to both humans and other animals. Therefore, it is essential to implement appropriate public health measures to reduce the circulation of the pathogen between various hosts. [ABSTRACT FROM AUTHOR]

Bloodstream infection (BSI) caused by bacteria is highly pathogenic and lethal, and easily develops whole-body inflammatory state. Immediate identification of disease-causing bacteria can improve patient prognosis. Traditional testing methods are not only time-consuming, but such tests are limited to laboratories. Recombinase polymerase amplification combined with lateral flow dipstick (RPA-LFD) holds great promise for rapid nucleic acid detection, but the uncapping operation after amplification easily contaminates laboratories. Therefore, the establishment of a more effective integrated isothermal amplification system has become an urgent problem to be solved. In this study, we designed and fabricated a hermetically sealed integrated isothermal amplification system. Combining with this system, a set of RPA-LFD assays for detecting S. aureus, K. peneumoniae, P. aeruginosa, and H. influenza in BSI were established and evaluated. The whole process could be completed in less than 15 min and the results can be visualized by the naked eye. The developed RPA-LFD assays displayed a good sensitivity, and no cross-reactivity was observed in seven similar bacterial genera. The results obtained with 60 clinical samples indicated that the developed RPA-LFD assays had high specifcity and sensitivity for identifying S. aureus, K. peneumoniae, P. aeruginosa, and H. influenza in BSI. In conclusion, our results showed that the developed RPA-LFD assay is an alternative to existing PCR-based methods for detection of S. aureus, K. peneumoniae, P. aeruginosa, and H. influenza in BSI in primary hospitals. [ABSTRACT FROM AUTHOR]

Background: Venous blood gas sampling has replaced arterial sampling in many critically ill patients, though interpretation of venous pCO2 still remains a challenge. Lemoël et al., Farkas and Zeserson et al. have proposed models to estimate arterial pCO2 based on venous pCO2. Our objective was to externally validate these models with a new dataset. This was a prospective cross-sectional study of consecutive adult patients with a clinical indication for blood gas analysis in an academic emergency department in Sweden. Agreement of pairs was reported as mean difference with limits of agreement (LoA). Vital signs and lead times were recorded. Results: Two hundred and fifty blood gas pairs were collected consecutively between October 2021 and April 2022, 243 valid pairs were used in the final analysis [mean age 72.8 years (SD 17.8), 47% females]. Respiratory distress was the most common clinical indication (84% of all cases). The model of Farkas showed the best metrics with a mean difference between estimated and arterial pCO2 of − 0.11 mmHg (95% LoA − 6.86, + 6.63). For Lemoël the difference was 2.57 mmHg (95% LoA − 5.65, + 10.8), Zeserson 2.55 mmHg (95% LoA − 7.43, + 12.53). All three models showed a decrease in precision in patients with ongoing supplemental oxygen therapy. Conclusion: Arterial pCO2 may be accurately estimated in most patients based on venous blood gas samples. Additional consideration is required in patients with hypo- or hypercapnia or oxygen therapy. Thus, conversion of venous pCO2 may be considered as an alternative to arterial blood gas sampling with the model of Farkas being the most accurate. [ABSTRACT FROM AUTHOR]

Background: The need for arterial blood data in quantitative PET research limits the wider usability of this imaging method in clinical research settings. Image-derived input function (IDIF) approaches have been proposed as a cost-effective and non-invasive alternative to gold-standard arterial sampling. However, this approach comes with its own limitations—partial volume effects and radiometabolite correction among the most important—and varying rates of success, and the use of IDIF for brain PET has been particularly troublesome. Main body: This paper summarizes the limitations of IDIF methods for quantitative PET imaging and discusses some of the advances that may make IDIF extraction more reliable. The introduction of automated pipelines (both commercial and open-source) for clinical PET scanners is discussed as a way to improve the reliability of IDIF approaches and their utility for quantitative purposes. Survey data gathered from the PET community are then presented to understand whether the field's opinion of the usefulness and validity of IDIF is improving. Finally, as the introduction of next-generation PET scanners with long axial fields of view, ultra-high sensitivity, and improved spatial and temporal resolution, has also brought IDIF methods back into the spotlight, a discussion of the possibilities offered by these state-of-the-art scanners—inclusion of large vessels, less partial volume in small vessels, better description of the full IDIF kinetics, whole-body modeling of radiometabolite production—is included, providing a pathway for future use of IDIF. Conclusion: Improvements in PET scanner technology and software for automated IDIF extraction may allow to solve some of the major limitations associated with IDIF, such as partial volume effects and poor temporal sampling, with the exciting potential for accurate estimation of single kinetic rates. Nevertheless, until individualized radiometabolite correction can be performed effectively, IDIF approaches remain confined at best to a few tracers. [ABSTRACT FROM AUTHOR]

Buffered and effervescent alendronate (ALN-EFF) increases gastric pH and is reported to decrease the risk of gastrointestinal side effects compared to conventional formulations of alendronate (ALN). The clinical effectiveness of ALN-EFF, however, has not been investigated. This study aims to investigate if ALN-EFF is non-inferior to ALN in suppressing bone turnover markers (BTM). We conducted a 16-week prospective, randomized, open-label study comprising 64 postmenopausal women with BMD T-score < −1 naïve to osteoporosis treatment. Participants were randomized 1:1 to ALN or ALN-EFF. We collected blood samples at 0, 4, 8, and 16 weeks. Non-inferiority margin was determined as 12% (80% of efficacy retained), and an SD of 15% on change in CTx. CTx decreased by 58.2% ± 24.1% in the ALN group and by 46.9% ± 23.3% (CI − 38.42:− 55.35) in the ALN-EFF group (p = 0.08). The non-inferiority limit was 46.6%. With ALN-EFF the CI crosses the non-inferiority limit thus the test for non-inferiority was indeterminate. PINP decreased by 45.7 ± 22.6% in the ALN group and by 35.1 ± 20.7% in the ALN-EFF group (p = 0.07). Changes over time in the BTMs were not significantly different between the groups, p > 0.10 for both CTx and PINP. There was no difference in frequency of AEs or compliance between the two groups, but rate of discontinuation was lower with ALN-EFF. In conclusion, suppression of BTMs was not significantly different between the groups but formal non-inferiority could not be established. [ABSTRACT FROM AUTHOR]

Background: Heel prick is a commonly performed painful intervention in neonates. Though different devices are available, there is a need to compare the procedural pain response elicited by them. Objectives: To compare the neonatal pain response to three different heel prick devices; automatic lancet, manual lancet, and 26-gauge (G) hypodermic needle. Design: Parallel-group three-arm randomized controlled trial. Participants: Clinically stable neonates of gestational age >28 weeks and birth weight >800 g undergoing heel prick for estimation of random blood sugar. Methods: One hundred and eighty neonates were randomized to automatic lancet (n=59), manual lancet (n=59), or needle (n=62) groups between March, 2021 and August, 2022. The primary outcome was the premature infant pain profile-revised (PIPP-R) score. Secondary outcomes were post-intervention cerebral regional oxygen saturation (CrSO2), changes in CrSO2 (ΔCrSO2), the time for CrSO2 normalization using near-infrared spectroscopy, duration of audible cry, and the number of squeezes and pricks needed. Intention-to-treat analysis was done. Results: Median (IQR) of PIPP-R scores were comparable in the automatic lancet [6 (4, 7.5)], manual lancet [5.5 (3.5, 8)], and needle [6 (3–9.6)] groups; P=0.59. No difference was observed in post-intervention CrSO2, ΔCrSO2 and the number of pricks. However, the time required for CrSO2 normalization and the number of squeezes were significantly higher with the needle. Conclusions: All three devices induced similar pain responses to heel prick in neonates; though, the number of squeezes needed was higher with the needle. [ABSTRACT FROM AUTHOR]

Background: Acute phase reactants (APR) are markers of inflammation that could be applied for the assessment of community-acquired pneumonia (CAP) severity in association with various pneumonia severity scores. So, the aim of the study was to assess levels of APR such as total leucocytic count (TLC), platelets, neutrophils, neutrophils-to-lymphocyte ratio (NLR), CRP, D-dimer, ferritin, and ESR in patients with CAP and to correlate between their values and disease severity. Methodology: The study included 51 patients diagnosed as non-COVID-19 (CAP). Patients were classified into two groups group A (pneumonia only) and group B (pneumonia complicated with empyema/complicated para-pneumonic effusion). All patients underwent clinical evaluation, CURB65, radiological assessment, and blood sampling to measure APR. Results: The mean age of patients was 47 ± 17 years. The main symptoms were productive cough (90.2%) and Fever (92.2%).TLC, platelets, neutrophils, CRP, D-dimer, ferritin, and ESR were elevated than normal values. Significant positive correlations were found between the duration of fever and CRP, D-dimer, and ferritin with p values = 0.024, 0.012, and 0.034 respectively. Significant positive correlations were found between CURB65 and both CRP and ferritin with p values = 0.007 and 0.020. A significant increase in platelet count and ESR values was found in group B than in group A. Conclusion: APR are important markers that can be used in the assessment of CAP in collaboration with clinical evaluation and severity scores. CRP, D-dimer, and ferritin were positively correlated with CURB65, while ESR and platelets could be considered predictors of the development of complications. Trial registration: Retrospectively registered, registration number NCT05926089, date of registration is 06/29/2023. [ABSTRACT FROM AUTHOR]