LC-MS/MS quantification of olanzapine in hair after alkaline digestion.

Olanzapine (OLZ), a second-generation antipsychotic drug, is effective in the treatment of acute psychosis, schizophrenia, agitation, bipolar mania, and other psychiatric problems. Antipsychotics are prescribed drugs, which lead the drug abuser to illegal methods of access. This behavior also demonstrates the association of OLZ with criminal involvement, commonly observed at forensic crime scenes. The acute toxicity and even death resulting from OLZ exposure have been highlighted in numerous studies. Therefore, developing analytical techniques to detect OLZ is essential for forensic toxicology. This study aimed to develop a specific and reliable LC-MS/MS method for OLZ detection and quantification in hair samples. The method was validated in terms of selectivity, linearity, limit of detection (LOD), limit of quantification (LOQ), trueness, precision, and uncertainty. The range of linearity was between 0.1-100 ng/mg, with LOD and LOQ values established at 0.036 ng/mg and 0.1 ng/mg, respectively. All validation results are within acceptable parameters. The validated method has been applied to authentic hair samples. The variation of OLZ concentrations in 12 hair segments (2 from Case 1 and 10 from Case 2) from two drug-positive patients, ranging from 0.131 to 0.460 ng/mg, is presented in this study. Although several studies have been conducted to determine OLZ in hair samples using segmental analysis via hair solubilization, this study is the first to determine OLZ in hair samples after "digestion" with comparative parameters prior to chromatographic analysis.

Pre-enrichment-free detection of hepatocellular carcinoma-specific ctDNA via PDMS and MEMS-based microfluidic sensor.

The growing interest in microfluidic biosensors has led to improvements in the analytical performance of various sensing mechanisms. Although various sensors can be integrated with microfluidics, electrochemical ones have been most commonly employed due to their ease of miniaturization, integration ability, and low cost, making them an established point-of-care diagnostic method. This concept can be easily adapted to the detection of biomarkers specific to certain cancer types. Pathological profiling of hepatocellular carcinoma (HCC) is heterogeneous and rather complex, and biopsy samples contain limited information regarding the tumor and do not reflect its heterogeneity. Circulating tumor DNAs (ctDNAs), which can contain information regarding cancer characteristics, have been studied tremendously since liquid biopsy emerged as a new diagnostic method. Recent improvements in the accuracy and sensitivity of ctDNA determination also paved the way for genotyping of somatic genomic alterations. In this study, three-electrode (Au-Pt-Ag) glass chips were fabricated and combined with polydimethylsiloxane (PDMS) microchannels to establish an electrochemical microfluidic sensor for detecting c.747G > T hotspot mutations in the TP53 gene of ctDNAs from HCC. The preparation and analysis times of the constructed sensor were as short as 2 h in total, and a relatively high flow rate of 30 µl/min was used during immobilization and hybridization steps. To the best of our knowledge, this is the first time a PDMS-based microfluidic electrochemical sensor has been developed to target HCC ctDNAs. The system exhibited a limit of detection (LOD) of 24.1 fM within the tested range of 2-200 fM. The sensor demonstrated high specificity in tests conducted with fully noncomplementary and one-base mismatched target sequences. The developed platform is promising for detecting HCC-specific ctDNA at very low concentrations without requiring pre-enrichment steps.

Evaluation of the Relationship Between Oral Health and Body Mass Index.

OBJECTIVE: The objectives of this study is to evaluate oral health comparatively in four different groups separated according to body mass index (BMI). MATERIALS AND METHODS: A total of 352 patients who applied for different dental reasons were divided into groups according to BMI and examined radiologically. The incidence of oral health parameters (dental caries, alveolar bone loss, tooth loss, and periapical lesion) was evaluated. RESULTS: While there was a significant difference between the groups in terms of caries, alveolar bone loss, and tooth loss (P < .05), there was no difference in the incidence of periapical lesions (P > .05). CONCLUSION: Obese individuals have a higher prevalence of alveolar bone loss, caries, and tooth loss. These results show that an above-normal BMI is an important factor that can negatively affect oral health.

An analytical approach to determining pethidine: An investigation of 18 patients' urine.

Pethidine (PET) is an opioid pain-relief medicine with high addiction potential, especially among health professionals. Pethidine is commonly prescribed in Turkey as a pain-relieving medication for operative purposes. Due to its accessibility, low cost, user-friendliness, and effectiveness, PET is often misused by both healthcare professionals and patients. For this reason, analytical determination methods for PET abuse are essential in terms of forensic toxicology. In this study, a fast, reliable, and accurate gas chromatography-mass spectrometry method was developed for the first time in Turkey for the simultaneous detection of PET and its main urinary metabolite norpethidine (NPET). The method was validated in terms of selectivity, linearity, the limit of detection (LOD), the limit of quantification (LOQ), trueness, and precision according to the Scientific Working Group for Forensic Toxicology guidelines. The linear range was between 0.125-25.00 µg/mL for PET and 1.00-20.00 µg/mL for NPET. The LOD values for PET and NPET were 0.05 µg/mL and 0.49 µg/mL, while the LOQ values were 0.125 µg/mL and 1.00 µg/mL, respectively. Extraction efficiencies were calculated as 113% for PET and 104% for NPET. The intra-assay and inter-assay precision results were within acceptable limits. In the presented study, the validated method was applied to the urine of 18 patients collected at the 1st and 3rd hours after receiving PET. All samples in the study were collected under patients' consent and in line with ethical guidelines.

The diagnostic value of n-terminal probrain natriuretic peptides to differentiate neonatal pneumoniae and transient tachypnea of the newborn.

BACKGROUND: The primary objective of the study was to determine the diagnostic value of serum N-terminal probrain natriuretic peptide (NT-proBNP) levels to differentiate neonatal pneumonia (NP) and transient tachypnea of the newborn (TTN). The secondary objective was to investigate the prognostic role of NT-proBNP levels in neonates with severe respiratory distress (RD). METHODS: A prospective, observational, single-blinded study involving 58 late preterm and term newborns who were diagnosed with TTN or NP was conducted between June 2020 and June 2021 at a level-3 neonatal intensive care unit in Kirikkale University Faculty of Medicine. TTN and NP groups were compared for serum NT-proBNP levels measured at the 1st and 24th hours of life. Optimal cut-off NT-proBNP value was determined by Youden index to predict the diagnosis of NP. Lung ultrasound was used to support the diagnosis of TTN and NP. In addition, lung ultrasound score (LUS) was used to determine severe RD. RESULTS: The median of NT-proBNP level was significantly higher at the 24th hour of life in the NP group than in the TTN group, respectively 7263.5 pg/mL (1643-35,000) and 3308 pg/mL (69-19,746), p = 0.004. At a cut-off value of 5515.5 pg/mL, NT-proBNP had a sensitivity of 75% and specificity of 73.8% to predict NP [AUC= 0.749 (95% CI: 0.602-0.895; p = 0.004)]. The study population was divided into two groups as high score group (n: 23, LUS ≥ 7) and low score group (n: 35, LUS < 7) according to the LUS at the 6th hour of life. NT-proBNP values at 24th hour of life were 6320 pg/mL (69-35,000) in high score group and 3500 pg/mL (570-15,948) in low score group, p = 0.044. Duration of oxygen support (p = 0.006), noninvasive ventilation (p = 0.008) and NICU stay (p = 0.004) were higher in high-score group. DISCUSSION: NT-proBNP values at 24th hour of life can be used as a relatively early predictor in the differentiation between NP and TTN in late preterm and term neonates. In addition, elevated NT-proBNP values are related to the higher LUS which reflects the severity of RD regardless of diagnosis.

Evaluation of the thickness and internal structure of the masseter muscle with ultrasonography in female bruxism patients.

OBJECTIVES: The aim of this study was to evaluate the differences in the thickness and internal structure of the masseter muscle in individuals with and without bruxism by ultrasonography. MATERIALS AND METHODS: A total of 60 female patients with and without bruxism whose ages were ranging between 20 and 35 were included in the study. The masseter muscle thickness was measured during rest and maximum bite position. Ultrasonographic internal structure of the masseter muscle is classified according to the visibility of echogenic bands. In addition, the echogenic internal structure of the masseter muscle was evaluated with quantitative muscle ultrasound. RESULTS: The masseter muscle thickness was significantly higher in both positions in patients with bruxism (p < 0.05). There was no significant difference between two groups in the evaluation of echogenicity (p > 0.05). CONCLUSIONS: Ultrasonography is a useful and important diagnostic method for evaluating masseter muscle without using radiation.

Microfluidic-based blood immunoassays.

Microfluidics enables the integration of whole protocols performed in a laboratory, including sample loading, reaction, extraction, and measurement steps on a single system, which offers significant advantages thanks to small-scale operation combined with precise fluid control. These include providing efficient transportation mechanisms and immobilization, reduced sample and reagent volumes, fast analysis and response times, lower power requirements, lower cost and disposability, improved portability and sensitivity, and greater integration and automation capability. Immunoassay is a specific bioanalytical method based on the interaction of antigens and antibodies, which is utilized to detect bacteria, viruses, proteins, and small molecules in several areas such as biopharmaceutical analysis, environmental analysis, food safety, and clinical diagnostics. Because of the advantages of both techniques, the combination of immunoassays and microfluidic technology is considered one of the most potential biosensor systems for blood samples. This review presents the current progress and important developments in microfluidic-based blood immunoassays. After providing several basic information about blood analysis, immunoassays, and microfluidics, the review points out in-depth information about microfluidic platforms, detection techniques, and commercial microfluidic blood immunoassay platforms. In conclusion, some thoughts and future perspectives are provided.

Visible Light Induced Degradation of Poly(methyl methacrylate-co-methyl α-chloro acrylate) Copolymer at Ambient Temperature.

Poly(methyl methacrylate) (PMMA) is a well-known and widely used commodity plastic. High production amount of PMMA causes excessive waste creation that highlights the necessity of recycling. Conventional recycling methods require elevated temperatures to induce degradation or depolymerization. In this work, visible light induced photodegradation system by using dimanganese decacarbonyl (Mn2 (CO)10 ) with high halogen affinity is reported. Halide functional photodegradable polymers are prepared by copolymerization of methyl methacrylate and methyl α-chloroacrylate by conventional reversible addition-fragmentation chain-transfer polymerization. Synthesized copolymers are efficiently degraded to low molecular weight oligomers under visible light irradiation in the presence of Mn2 (CO)10 . Characteristics of precursors, degraded polymers, and kinetics of depolymerization are investigated by gel permeation chromatography (GPC), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourrier transform infrared (FTIR), and proton nuclear magnetic resonance (1 H-NMR) spectroscopies. The reported approach is expected to trigger further development of more environmentally friendly recycling techniques in the near future as we  are moving toward a greener and more sustainable world.

Probable bruxism effects on masseter muscle thickness in children: ultrasonographic evaluation.

OBJECTIVE: To compare the masseter muscle thickness (MMT) of patients with probable sleep/awake bruxism and controls without bruxism in mixed dentition as measured with ultrasonography (USG), and to calculate the correlation of MMT with body mass index (BMI). STUDY DESIGN: The diagnosis of probable bruxism was established based on the parents' reports of the children's behavior, habits, and discomfort, and the presence of clinical signs and symptoms such as attrition-type wear on the teeth and the presence of discomfort, fatigue, and/or pain in the jaw muscles on palpation during clinical examination. The bruxist study group and the control group each included 28 children. MMT was measured separately in relaxed and contracted positions in both groups using USG. The height and weight of the patients were recorded in order to calculate BMI. Statistical analysis was performed with significance established at P < .05. RESULTS: MMT was found to be significantly larger in the study patients than in controls on the right and left sides in the relaxed and contracted positions (P < .001). No statistically significant correlation was found between MMT and BMI (P ≥ .134). CONCLUSIONS: MMT as measured with USG can be a beneficial approach in diagnosing bruxism in children. The lack of correlation between MMT and BMI indicates that BMI would not be helpful in diagnosing bruxism.

Clinical features and management of animal bites in an emergency department: a single-center experience.

OBJECTIVES: This study aimed to evaluate the clinical features, management, and outcomes of patients with animal bites presented to the pediatric emergency department of a tertiary center. METHODS: Patients with ICD-10 code W54 (contact with dog) and W55 (contact with other mammals) between March 1st, 2017, and July 1st, 2021, were included in the study. Demographic characteristics of the patients, type of contacted animal, wound characteristics (muscle involvement, soft tissue defect, vascular injury, type of nerve injury, and Lackmann's classification), wound care measurements, tetanus prophylaxis, administration of rabies immunoglobulin and antibiotics, location of the injury, existing fractures, suturing, splinting, surgical consultations and hospitalization status were recorded. RESULTS: Four hundred and nineteen incidents of animal bites (240 males and 179 females) occurred over a four-year period. 51% was due to a dog bite; 47% was by a cat. The median age was nine years (IQR: 5-14 years). Most bites (91.6%) involved only a single anatomical site. The extremities were the commonly involved part (right upper limb [35.3%], left upper limb [21.2%], right lower limb [12.6%], left lower limb [16%]). Head-neck and face injury ratio was 17.6%. Torso (5.7%) and genitalia (5.2%) were uncommonly involved. A consultation was requested from at least one surgical department for 8% of the patients. 97.1% of patients received a rabies vaccine. Most attacks were trivial and did not require hospitalization. CONCLUSION: Animal bites often cause minor injuries. However, multiple dog attacks can be seen related to a high number of stray animals in our country. Therefore, these patients may present with major traumas. Surgical intervention and hospitalization may be required. Emergency physicians play an essential role in acute management and rabies prophylaxis in these patients.

Dimanganese decacarbonyl catalyzed visible light induced ambient temperature depolymerization of poly(methyl methacrylate).

Recent years have witnessed an enormous development in photoinduced systems, opening up possibilities for advancements in industry and academia in terms of green chemistry providing environmentally friendly conditions and spatiotemporal control over the reaction medium. A vast number of research have been conducted on photoinduced systems focusing on the development of new polymerization methods, although scarcely investigated, depolymerization of the synthesized polymers by photochemical means is also possible. Herein, we provide a comprehensive study of visible light induced dimanganese decacarbonyl (Mn2(CO)10) assisted depolymerization system for poly(methyl methacrylate) with chlorine chain end prepared by Atom Transfer Radical Polymerization. Contrary to the conventional procedures demanding high temperatures, the approach offers ambient temperature for the photodepolymerization process. This novel light-controlled concept is easily adaptable to macroscales and expected to promote further research in the fields matching with the environmental concerns.

Issues related to post-COVID-19 syndrome.

The pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 2019-2022 leads to a multisystem illness that results in damage to numerous organ systems. In this review, our goal was to assess current research on long-term respiratory, cardiac, neurological, digestive, rheumatological, urogenital, and dermatological system complications of coronavirus disease 2019 (COVID-19). Bibliographic searches were conducted in December 2021 using PubMed and Google Scholar, retrospectively, covering all COVID-19 literature to determine the consequences of the disease. This review may help to determine the prospects for new studies and predict the upcoming aspects requiring assessment in post-COVID-19 syndrome.

Reconsidering the Relationship Between Hand Preference and Cerebral Vascular Dominance: A Computed Tomography (CT) Angiography Study.

Background: To date, it has been suggested that there may be many genetic, environmental, and vascular factors that affect hand preference. In previous studies evaluating the relationship between cerebral dominance and hand preference, carotid and vertebral artery (VA) Doppler ultrasonography (USG) was generally preferred; and these studies only measured VA diameters. Unlike other studies, we aimed to reevaluate the relationship between hand preference and cerebral vascular dominance by measuring VA and internal carotid artery (ICA) diameters. In addition, we used carotid and VA computed tomography (CT) angiography instead of Doppler USG. Methods and Material: A total of 345 participants were included in the study. The results of carotid and VA CT angiography taken during hospitalization were retrospectively evaluated by two radiologists, and the Edinburgh Hand Preference Questionnaire was applied to these patients. Results: In right-handed patients, the diameter of the left VA was significantly larger than the diameter of the right VA (p = 0.005). In left-handed patients, the diameter of the left ICA was larger than the diameter of the right ICA, but the difference was not statistically significant (p = 0.055). There was no significant difference between the diameter of the right and left ICA in right-handed patients (p = 0.771). Conclusions: In our study, we found a correlation between the dominant hemisphere VA diameter and hand preference. Using CT angiography, we were able to eliminate many challenges of ultrasonography that make radiological evaluation difficult, such as differences of opinion between radiologists, and technical and anatomical reasons.

Label-free enrichment of MCF7 breast cancer cells from leukocytes using continuous flow dielectrophoresis.

Circulating tumor cells (CTCs) present in the bloodstream are strongly linked to the invasive behavior of cancer; therefore, their detection holds great significance for monitoring disease progression. Currently available CTC isolation tools are often based on tumor-specific antigen or cell size approaches. However, these techniques are limited due to the lack of a unique and universal marker for CTCs, and the overlapping size between CTCs and regular blood cells. Dielectrophoresis (DEP), governed by the intrinsic dielectric properties of the particles, is a promising marker-free, accurate, fast, and low-cost technique that enables the isolation of CTCs from blood cells. This study presents a continuous flow, antibody-free DEP-based microfluidic device to concentrate MCF7 breast cancer cells, a well-established CTC model, in the presence of leukocytes extracted from human blood samples. The enrichment strategy was determined according to the DEP responses of the corresponding cells, obtained in our previously reported DEP spectrum study. It was based on the positive-DEP integrated with hydrodynamic focusing under continuous flow. In the proposed device, the parylene microchannel with two inlets and outlets was built on top of rectangular and equally spaced isolated planar electrodes rotated certain degree relative to the main flow (13°). The recovery of MCF7 cells mixed with leukocytes was 74%-98% at a frequency of 1 MHz and a magnitude of 10-12 Vpp . Overall, the results revealed that the presented system successfully concentrates MCF7 cancer cells from leukocytes, ultimately verifying our DEP spectrum study, in which the enrichment frequency and separation strategy of the microfluidic system were determined.

RNA sequencing of blood in coronary artery disease: involvement of regulatory T cell imbalance.

BACKGROUND: Cardiovascular disease had a global prevalence of 523 million cases and 18.6 million deaths in 2019. The current standard for diagnosing coronary artery disease (CAD) is coronary angiography. Surprisingly, despite well-established clinical indications, up to 40% of the one million invasive cardiac catheterizations return a result of 'no blockage'. The present studies employed RNA sequencing of whole blood to identify an RNA signature in patients with angiographically confirmed CAD. METHODS: Whole blood RNA was depleted of ribosomal RNA (rRNA) and analyzed by single-molecule sequencing of RNA (RNAseq) to identify transcripts associated with CAD (TRACs) in a discovery group of 96 patients presenting for elective coronary catheterization. The resulting transcript counts were compared between groups to identify differentially expressed genes (DEGs). RESULTS: Surprisingly, 98% of DEGs/TRACs were down-regulated ~ 1.7-fold in patients with mild to severe CAD (> 20% stenosis). The TRACs were independent of comorbid risk factors for CAD, such as sex, hypertension, and smoking. Bioinformatic analysis identified an enrichment in transcripts such as FoxP1, ICOSLG, IKZF4/Eos, SMYD3, TRIM28, and TCF3/E2A that are likely markers of regulatory T cells (Treg), consistent with known reductions in Tregs in CAD. A validation cohort of 80 patients confirmed the overall pattern (92% down-regulation) and supported many of the Treg-related changes. TRACs were enriched for transcripts associated with stress granules, which sequester RNAs, and ciliary and synaptic transcripts, possibly consistent with changes in the immune synapse of developing T cells. CONCLUSIONS: These studies identify a novel mRNA signature of a Treg-like defect in CAD patients and provides a blueprint for a diagnostic test for CAD. The pattern of changes is consistent with stress-related changes in the maturation of T and Treg cells, possibly due to changes in the immune synapse.

A Case Report of a Prenatally Missed Mowat-Wilson Syndrome With Isolated Corpus Callosum Agenesis.

Mowat-Wilson syndrome (MWS) is an autosomal dominant genetic disorder caused by ZEB2 gene mutations, manifesting with unique facial characteristics, moderate to severe intellectual problems, and congenital malformations as Hirschsprung disease, genital and ophthalmological anomalies, and congenital cardiac anomalies. Herein, a case of 1-year-old boy with isolated agenesis of corpus callosum (IACC) in the prenatal period is presented. He was admitted postnatally with Hirschsprung disease (HSCR), hypertelorism, uplifted earlobes, deeply set eyes, frontal bossing, oval-shaped nasal tip, ''M'' shaped upper lip, opened mouth and prominent chin, and developmental delay. Hence, MWS was primarily considered and confirmed by the ZEB2 gene mutation analysis. His karyotype was normal. He had a history of having a prenatally terminated brother with similar features. Antenatally detected IACC should prompt a detailed investigation including karyotype and microarray; even if they are normal then whole exome sequencing (WES) should be done.

Sequencing Therapies for Metastatic Renal Cell Carcinoma.

In an era of several therapeutic options available, optimal treatment sequencing is crucial to providing patients the most effective therapy and promoting quality of life. In clear cell renal cell carcinoma, a combination approach with an immunotherapy backbone, such as nivolumab/ipilimumab or axitinib/pembrolizumab, has a key role in the first-line setting. Safety and activity data support the transition to single-agent targeted therapies in the second-line setting. Nivolumab monotherapy possesses clinical and mechanistic rationale as a second-line therapeutic option for patients treated with targeted therapies in the first-line setting. Gene expression models are being generated from large prospective clinical trial data sets.