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Aims: While the prevalence of transthyretin-derived amyloid cardiomyopathy (ATTR-CM) is on the rise, detailed understanding of its morphological and functional characteristics within the left ventricle (LV) across heart failure (HF) remains limited. Methods and results: Utilizing two-dimensional (2D) speckle-tracking echocardiography, we assessed longitudinal strain (LS) in 63 histology-confirmed ATTR-CM patients. Additionally, cardiac magnetic resonance (CMR) images measured native T1 and extracellular volume (ECV), compared with LS across 18 LV segments. Patients were categorized into three groups based on HF status: Group 1 (no HF symptoms), Group 2 (HF with preserved LV ejection fraction), and Group 3 (HF with reduced LV ejection fraction). LS analysis unveiled susceptibility to deformation in the basal inferoseptal segment, persisting even in asymptomatic cases. CMR demonstrated increasing native T1 deviation, particularly evident in segments distant from the inferoseptal region. Contrastingly, maximal ECV was consistently observed in the basal and mid-ventricular inferior-septum, even in asymptomatic individuals. Segmental LS decline correlated with ECV expansion but not with native T1 values. Conclusion: Our findings suggest that the inferoseptal segment is highly susceptible to amyloid infiltration, and 2D speckle-tracking echocardiography and CMR may serve as a valuable tool for its early detection.

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PURPOSE: We previously developed evaluation methods using micro-segmental analysis (MSA) to examine the effects of external environments on drug content in hair and nails. In this study, the effects of the natural environmental factors (water, temperature, humidity, light, and soil) on drug contents in nails were examined and compared with our previous experimental data on hair. METHODS: Four hay-fever medicines were used as model drugs (fexofenadine, epinastine, cetirizine, and desloratadine) to evaluate drug stability in the nails. Reference nails containing the four medicines were collected from patients with hay fever who ingested the medicines daily for four months. The nails were exposed to various natural environments for up to four months. RESULTS: The effects of temperature, humidity, and light on drug contents in the nails were comparatively small. Soil significantly decomposed the nail surfaces and decreased the drug content of the nails (up to 17 %). Water also decreased the drug content (up to 12 %), although no apparent changes in nail surfaces were observed. CONCLUSIONS: In comparison with hair data obtained under the same environmental conditions, light affected drugs in the hair rather than in nails, whereas water and soil greatly affected drugs in the nails rather than in hair. Although the disposition of drugs incorporated in the tissues differed between nails and hair, the analytes were detected in nails and hair strands left in severe natural environments. MSA could be useful for estimating drug-use histories and personal profiles using the nails and hair of a corpse.

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The traditional description of cardiac development involves progression from a cardiac crescent to a linear heart tube, which in the phase of transformation into a mature heart forms a cardiac loop and is divided with the septa into individual cavities. Cardiac morphogenesis involves numerous types of cells originating outside the initial cardiac crescent, including neural crest cells, cells of the second heart field origin, and epicardial progenitor cells. The development of the fetal heart and circulatory system is subject to regulatation by both genetic and environmental processes. The etiology for cases with congenital heart defects (CHDs) is largely unknown, but several genetic anomalies, some maternal illnesses, and prenatal exposures to specific therapeutic and non-therapeutic drugs are generally accepted as risk factors. New techniques for studying heart development have revealed many aspects of cardiac morphogenesis that are important in the development of CHDs, in particular transposition of the great arteries.

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Nails can be used as an alternative to hair for examining past drug use. However, daily hand-and-nail care can eliminate the internal drugs. Therefore, we developed an evaluation method to examine the effects of the external environment on drug stability in nails using micro-segmental analysis. First, reference nails containing drugs were prepared by collecting fingernails from participants who had consumed hay-fever medicines continuously for 4 months. Next, the entire free edge of a reference nail was cut into halves at the centerline; one side was stored as an untreated block, and the other was treated with various hand/nail care products. Both nail blocks were washed and segmented at 0.5-mm intervals in the width direction. Each segment in the extraction solution was crushed with stainless-steel beads, sonicated, and soaked in the solution for 24 h. The analytes in extracts were quantified by LC-MS/MS, and the drug concentrations between the treated and untreated blocks were compared. The drug concentrations decreased slightly in nails treated with manicure and gel-nail products. The analytes in nails tended to be lower in water-rich products such as hand soap and hand cream than in oil-rich products such as nailcare oil and acetone-free remover. The developed method using micro-segmental analysis enabled the evaluation of the effects of various hand/nail care products on drug stability in a limited number of nails. This would also be useful for examining the effects of severe environments on drugs in nails collected from cases of unnatural death.

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Segmental analyses of hair may be useful for measuring biomarkers over several seasons to years from a single sample. To attribute hair segments to specific time periods, a known chronological marker, or a hair growth rate, is needed. We examined guard hair growth rates of captive muskoxen (Ovibos moschatus) in Fairbanks, Alaska, USA. We sought to determine if a general growth rate could be applied across muskox populations, thus facilitating the use of segmental analyses for various biomarkers. We used archived samples from 16 muskoxen that had guard hairs sampled at six, 14, and 30 wk after shaving. We measured the lengths of 10 guard hairs per sample, calculated weekly and annual growth rates, and then fitted linear mixed-effects models to assess the effect of different covariates on hair growth rate. The period in which hair had been grown had a significant effect (P<0.05) on growth rate. Extrapolated annual hair growth rates were 277±40 mm/yr (weeks 0-6), 248±47 mm/yr (weeks 7-14), and 165±36 mm/yr (weeks 15-30), with an overall average rate of 210±14 mm/yr. These rates were significantly faster than those of free-ranging Greenland muskoxen-78 mm/yr as measured by stable isotope analyses-and varied intra-annually. This suggests that a universal growth rate cannot be generalized across muskox populations and time.

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Body composition and phase angle (PhA) have been used to predict mortality in multiple diseases. However, little has been studied regarding segmental measurements, which could potentially help assess subtle changes in specific tissue segments. This study aimed to identify the total PhA cut-off point associated with mortality risk and changes in body composition within a week of hospitalisation in non-critical hospitalised patients with COVID-19. A cohort study was conducted where patients underwent to a complete nutritional assessment upon admission and after seven days, and followed up until hospital discharge or death. A receiver operating characteristic curve was constructed to determine the PhA cut-off point, and the Kaplan­Meier estimator was used to determine survival analysis. Segmental and complete body compositions on admission and after 7 d were compared. We included 110 patients (60 men) with a mean age of 50·5 ± 15·0 years and a median BMI of 28·5 (IQR, 25·6­33·5) kg/m2. The median length of hospital stay was 6 (IQR, 4­9) d, and the mortality rate was 13·6 %. The PhA cut-off point obtained was 4°, with significant differences in the survival rate (P < 0·001) and mortality (HR = 5·81, 95 % CI: 1·80, 18·67, P = 0·003). Segmental and whole-body compositions were negatively affected within one week of hospitalisation, with changes in the approach by the graphical method in both sexes. Nutritional status deteriorates within a week of hospitalisation. PhA < 4° is strongly associated with increased mortality in non-critical hospitalised patients with COVID-19.

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Introduction: Hair testing is well established for the assessment of past drug exposure; however, more research is needed to understand drug incorporation mechanisms and drug entry pathways into hair. Method: In this study, a micro-segmental LC-MS/MS method was used to analyze a 0.4 mm segment of hair after a single oral administration of zolpidem. Five single hairs were plucked at 1 day, 3 days, 7 days, and 28 days after administration from the vertex posterior of three subjects, and 5 single hairs were also plucked from the parietal, left temporal, and right temporal regions of the head at 28 days. Results and discussion: Proximal S1 (0-0.4 mm) in hair plucked at 1 day had the highest level of zolpidem at 1.5-2.4 pg/mm; much lower concentrations (< 1 pg/mm) were detected at proximal S2-S8 (0.4-3.2 mm). The drug concentration decreased gradually in S1 for 7 days after drug intake and disappeared by 28 days, suggesting that the drug from the bloodstream initially combined with the hair follicle and then gradually moved to the hair tip as the hair grew. The zolpidem concentration-hair segment profiles exhibited a large peak (root side) and a small peak (tip side) for the four sampling times in all three subjects, indicating that drug incorporation in the hair bulb occurred mainly from the blood but probably also entered the hair through sweat and sebum. Zolpidem was also detected in all hairs from the vertex posterior in all three subjects but was not detected in 1 hair from the parietal region and 2 hairs from the left temporal region. The consistency in drug detection, drug concentration level, and peak position was better in hair from the vertex posterior than from the other three regions, indicating that the vertex posterior is a suitable sampling region for estimating drug intake.

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PURPOSE: Micro-segmental analysis (MSA), which enables the measurement of detailed drug distributions in hair by segmenting a single hair strand at 0.4 mm intervals, is indispensable for estimating the day of drug ingestion. However, haircare with dryers and various products can influence drug concentrations in hair. Therefore, the applicability of MSA to hair that was treated with heat or various haircare products was evaluated. METHODS: Reference hair strands containing drugs consistently along the hair shafts were collected from patients who ingested four hay-fever medicines (fexofenadine, epinastine, cetirizine, and loratadine) daily for 4 months. The hair strands were divided into eight 4 mm regions from the proximal end, and each region was placed on an electric hot plate at 100-200 °C or soaked in haircare products, such as shampoo and bleaching agent. The hair regions were subjected to MSA. Moreover, after a patient was administered midazolam at a single dose and the hair was bleached, the day of midazolam administration was estimated using MSA. RESULTS: Repetitive heating for 1 min and daily haircare products, such as shampoo, hardly affected the drugs in hair, whereas bleaching products containing H2O2 decreased the amounts of hay-fever medicines in the hair up to 58%. However, the amount of midazolam did not decrease in bleached hair and the day of midazolam administration was successfully estimated. CONCLUSIONS: The analytes used in this study were minimally affected by ordinary haircare and could be detected even in bleached hair. Therefore, MSA can be applicable regardless of haircare history.

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PURPOSE: Since the 1980s, the detection sensitivity of mass spectrometers has increased by improving the analysis of drugs in hair. Accordingly, the number of hair strands required for the analysis has decreased. The length of the hair segment used in the analysis has also shortened. In 2016, micro-segmental hair analysis (MSA), which cuts a single hair strand at a 0.4-mm interval corresponding to a hair growth length of approximately one day, was developed. The advantage of MSA is that the analytical results provide powerful evidence of drug use in the investigation of drug-related crimes and detailed information about the mechanism of drug uptake into hair. This review article focuses on the MSA technique and its applications in forensic toxicology. METHODS: Multiple databases, such as SciFinder, PubMed, and Google, were utilized to collect relevant reports referring to MSA and drug analysis in hair. The experiences of our research group on the MSA were also included in this review. RESULTS: The analytical results provide a detailed drug distribution profile in a hair strand, which is useful for examining the mechanism of drug uptake into hair in detail. Additionally, the analytical method has been used for various scenarios in forensic toxicology, such as the estimation of days of drug consumption and death. CONCLUSIONS: The detailed procedures are summarized so that beginners can use the analytical method in their laboratories. Moreover, some application examples are presented, and the limitations of the current analytical method and future perspectives are described.

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[This corrects the article DOI: 10.3389/fnut.2022.873623.].

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Transthoracic echocardiography is an essential tool in the diagnosis, assessment, and management of paediatric and adult populations with suspected or confirmed congenital heart disease. Congenital echocardiography is highly operator-dependent, requiring advanced technical acquisition and interpretative skill levels. This document is designed to complement previous congenital echocardiography literature by providing detailed practical echocardiography imaging guidance on sequential segmental analysis, and is intended for implementation predominantly, but not exclusively, within adult congenital heart disease settings. It encompasses the recommended dataset to be performed and is structured in the preferred order for a complete anatomical and functional sequential segmental congenital echocardiogram. It is recommended that this level of study be performed at least once on all patients being assessed by a specialist congenital cardiology service. This document will be supplemented by a series of practical pathology specific congenital echocardiography guidelines. Collectively, these will provide structure and standardisation to image acquisition and reporting, to ensure that all important information is collected and interpreted appropriately.

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Objective: To examine the changes in body composition, water compartment, and bioimpedance in mild cognitive impairment (MCI) individuals. Methods: We obtained seven whole-body composition variables and seven pairs of segmental body composition, water compartment, and impedance variables for the upper and lower extremities from the segmental multi-frequency bioelectrical impedance analysis (BIA) of 939 elderly participants, including 673 cognitively normal (CN) people and 266 individuals with MCI. Participants' characteristics, anthropometric information, and the selected BIA variables were described and statistically compared between the CN participants and those with MCI. The correlations between the selected BIA variables and neuropsychological tests such as the Korean version of the Mini-Mental State Examination and Seoul Neuropsychological Screening Battery - Second Edition were also examined before and after controlling for age and sex. Univariate and multivariate logistic regression analyses with estimated odds ratios (ORs) were conducted to investigate the associations between these BIA variables and MCI prevalence for different sexes. Results: Participants with MCI were slightly older, more depressive, and had significantly poorer cognitive abilities when compared with the CN individuals. The partial correlations between the selected BIA variables and neuropsychological tests upon controlling for age and sex were not greatly significant. However, after accounting for age, sex, and the significant comorbidities, segmental lean mass, water volume, resistance, and reactance in the lower extremities were positively associated with MCI, with ORs [95% confidence interval (CI)] of 1.33 (1.02-1.71), 1.33 (1.03-1.72), 0.76 (0.62-0.92), and 0.79 (0.67-0.93), respectively; with presumably a shift of water from the intracellular area to extracellular space. After stratifying by sex, resistance and reactance in lower extremities remained significant only in the women group. Conclusion: An increase in segmental water along with segmental lean mass and a decrease in body cell strength due to an abnormal cellular water distribution demonstrated by reductions in resistance and reactance are associated with MCI prevalence, which are more pronounced in the lower extremities and in women. These characteristic changes in BIA variables may be considered as an early sign of cognitive impairment in the elderly population.

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A high-throughput method using microwave-assisted extraction, chemical derivatization and liquid chromatography-electrospray tandem mass spectrometry (LC-ESI-MS/MS) was developed for the simultaneous analysis of illicit drugs and their metabolites, including amphetamine (AMP), methamphetamine (MA), methylenedioxy- amphetamine (MDA), methylenedioxy-methamphetamine (MDMA), morphine (MOR), 6-acetylmorphine (6-AM), ketamine (K), and norketamine (NK) in a micro-segment of a single hair (0.4 mm). In order to elevate the throughput and sensitivities of selected compounds, 3 min microwave-assisted extraction and 10 min derivatization with dansyl chloride (DC) were employed. After derivatization, all compounds except ketamine and norketamine were derivatized and enhanced the sensitivities significantly. Derivatives showed intense fragment ions and low background noise on DC-MOR, DC-6-AM, and four DC-amphetamine-type stimulants. The total sample preparation and analysis time was 50 min. The calibration range was from LOQ to 5000 pg/mg, the coefficient of determination was better than 0.997. Intra-assay precision and accuracy were generally less than 15%. Limits of detection ranged from 15 to 50 pg/mg, limits of quantitation ranged between 45 and 125 pg/mg. The matrix effect was better than 90%. The method was successfully applied to the analysis of actual hair samples collected from multi-drug abusers. This advanced method showed practicality in hair analysis and was suitable for the extremely insufficient sample.

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INTRODUCTION: In adolescent idiopathic scoliosis (AIS) patients, mechanical consequences of posterior spinal fusion within the spine remain unclear. Through dynamic assessment, gait analysis could help elucidating this particular point. The aim of this study was to describe early changes within the spine following fusion with hybrid instrumentation in adolescents with idiopathic scoliosis, using gait analysis MATERIALS AND METHODS: We conducted a single-centre prospective study including AIS patients scheduled for posterior spinal fusion (PSF) using hybrid instrumentation with sublaminar bands. Patients underwent radiographic and gait analyses preoperatively and during early postoperative period. Among gait parameters, motion of cervicothoracic, thoracolumbar and lumbosacral junctions was measured in the three planes. RESULTS: We included 55 patients (mean age 15 years, 84% girls). Fusion was performed on 12 levels and mean follow-up was 8 months. There was a moderately strong correlation between thoracolumbar sagittal motion and lumbosacral junction pre- and postoperatively (R = - 0.6413 and R = - 0.7040, respectively, all p < 0.001), meaning that the more thoracolumbar junction was in extension, the more lumbosacral extension movements decreased. There was a trend to significance between postoperative SVA change and thoracolumbar sagittal motion change (R = - 0.2550, p = 0.059). DISCUSSION: This is the first series reporting dynamic changes within the spine following PSF using hybrid instrumentation in AIS patients. PSF led to symmetrization of gait pattern. In the sagittal plane, we found that thoracolumbar extension within the fused area led to decreased extension at cervicothoracic and lumbosacral junctions. Even though consequences of such phenomenon are unclear, attention must be paid not to give a too posterior alignment when performing PSF for AIS patients.

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BACKGROUND: The analysis of biomechanical parameters derived from the body center of mass (BCoM) 3D motion allows for the characterization of gait impairments in people with lower-limb amputation, assisting in their rehabilitation. In this context, magneto-inertial measurement units are promising as they allow to measure the motion of body segments, and therefore potentially of the BCoM, directly in the field. Finding a compromise between the accuracy of computed parameters and the number of required sensors is paramount to transfer this technology in clinical routine. RESEARCH QUESTION: Is there a reduced subset of instrumented segments (BSN) allowing a reliable and accurate estimation of the 3D BCoM acceleration transfemoral amputees? METHODS: The contribution of each body segment to the BCoM acceleration was quantified in terms of weight and similarity in ten people with transfemoral amputation. First, body segments and BCoM accelerations were obtained using an optoelectronic system and a full-body inertial model. Based on these findings, different scenarios were explored where the use of one sensor at pelvis/trunk level and of different networks of segment-mounted sensors for the BCoM acceleration estimation was simulated and assessed against force plate-based reference acceleration. RESULTS: Trunk, pelvis and lower-limb segments are the main contributors to the BCoM acceleration in transfemoral amputees. The trunk and shanks BSN allows for an accurate estimation of the sagittal BCoM acceleration (Normalized RMSE ≤ 13.1 %, Pearson's correlations r ≥ 0.86), while five segments are necessary when the 3D BCoM acceleration is targeted (Normalized RMSE ≤ 13.2 %, Pearson's correlations r ≥ 0.91). SIGNIFICANCE: A network of three-to-five segments (trunk and lower limbs) allows for an accurate estimation of 2D and 3D BCoM accelerations. The use of a single pelvis- or trunk-mounted sensor does not seem advisable. Future studies should be performed to confirm these results where inertial sensor measured accelerations are considered.

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To prove drug-related crimes, it is important to estimate the date on which a specific drug was ingested. Previously, we developed a method, "micro-segmental hair analysis," to estimate the day of ingestion of a single-dose drug by segmenting a hair strand into 0.4-mm segments, which correspond to daily hair growth. In this study, the method was improved to estimate the days of continuous drug ingestion. The subjects ingested four hay-fever medicines (fexofenadine, epinastine, cetirizine, and loratadine) continuously (1-18 days) and chlorpheniramine as a single dose at intervals of several weeks as an internal temporal marker (ITM). The hair strands of the subjects were collected and subjected to a micro-segmental analysis. The distribution curves of each hay-fever medicine in a hair strand had broad peaks reflecting the number of days of drug ingestion. The positions on the curves corresponding to the first and final ingestion days of hay-fever medicines were identified using the ITM. The positions were near the hair segments on both ends of full width at half maximum (W2 ) of the broad peak. When the first and final days of continuous ingestion were estimated using W2 , independent of peak shape, the absolute average error from the actual ingestion days was approximately 2 days. Overall, we established a method to estimate the days of both single-dose and continuous drug ingestions. Furthermore, the method would be useful to investigate drug ingestion history in various scenes such as drug-related crimes and therapeutic drug monitoring.

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PURPOSE: To perform a segmental analysis of tibial torsion in patients, with normal and increased external tibial torsion, suffering from chronic patellofemoral instability (PFI) and to investigate a possible correlation between tibial torsion and the position of the tibial tuberosity. METHODS: Patients with chronic PFI who underwent torsional analysis of the lower limb using a standardized hip-knee-ankle MRI between 2016 and 2018 were included. For segmental analysis of tibial torsion, three axial levels were defined which divided the tibia into two segments: a distal, infratuberositary segment and a proximal, supratuberositary segment. Torsion was measured for the entire tibia (total tibial torsion, TTT), the proximal segment (proximal tibial torsion, PTT), and the distal segment (distal tibial torsion, DTT). Based on TTT, patients were assigned to one of two groups: Normal TTT (< 35°) or increased external TTT (> 35°). Position of the tibial tuberosity was assessed on conventional MRI scans by measuring the tibial tuberosity-trochlea groove (TT-TG) and the tibial tuberosity-posterior cruciate ligament (TT-PCL) distances. RESULTS: Ninety-one patients (24 ± 6 years; 78% female) were included. Mean external TTT was 29.6° ± 9.1° and 24 patients (26%) had increased external TTT. Compared to patients with normal TTT, patients with increased external TTT demonstrated significantly higher values for DTT (38° ± 8° vs. 52° ± 9°; p < 0.001), whereas no difference was found for PTT ( - 13° ± 6° vs. - 12° ± 6°; n.s.). Furthermore, a significant correlation was found between TTT and DTT (p < 0.001), whereas no correlation was found between TTT and PTT (n.s). With regard to TT-TG and TT-PCL distances, no significant differences were observed between the two groups (TT-TG: 15 ± 6 vs. 14 ± 4 mm, n.s.; TT-PCL: 22 ± 4 vs. 21 ± 5 mm, n.s.) and no correlation was found with TTT, DTT, or PTT (n.s.). CONCLUSION: In patients with chronic PFI, increased external TTT of greater than 35° is an infratuberositary deformity and does not correlate with a lateralized position of the tibial tuberosity. LEVEL OF EVIDENCE: Level III.

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Hair analysis is capable of determining both an individual's long-term drug history and a single exposure to a drug, which can be particularly important for corroborating incidents of drug-facilitated crimes. As a source of forensic evidence that may be used in a court of law, it must be credible, impartial and reliable, yet the pathways of drug and metabolite entry into hair are still uncertain. Many variables may influence drug analysis results, most of which are outside of the control of an analyst. An individual's pharmacokinetic and metabolic responses, hair growth rates, drug incorporation routes, axial migration, ethnicity, age and gender, for example, all display interpersonal variability. At present there is little standardization of the analytical processes involved with hair analysis. Both false positives and negative results for drugs are frequently encountered, regardless of whether a person has consumed a drug or not. In this regard, we have categorized these variables and proposed a three-stage analytical approach to facilitate forensic toxicologists, hair analysis experts, judiciaries and service users in the analytical and interpretation process.

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Congenital heart disease is a rare but important finding in adults who experience sudden death. Examination of the congenitally malformed heart has historically been considered esoteric and best left to those with expertise. The Cardiac Risk in the Young cardiovascular pathology laboratory based at St George's University of London has now received over 6,000 cases. Of these, 21 congenitally malformed hearts were retained for research and educational purposes. Hearts were assessed using sequential segmental analysis, and causes of death were adjudicated based on thorough macroscopic examination and histology. Congenital malformations that were encountered included atrial septal defects, ventricular septal defects, tetralogy of Fallot, and transposition of the great arteries in both its regular and congenitally corrected variants. Findings also included hearts with mirror-imaged and isomeric atrial appendages. Direct causes of death included myocardial fibrosis, pulmonary hypertension, and hemorrhage. A small but notable proportion did not reveal a substrate for arrhythmia, raising the question of whether the terminal event was due to the congenital heart disease itself, or an underlying channelopathy. Here, we demonstrate the value of simple sequential segmental analysis in describing and categorizing the cases, with the concept of the "morphological method" serving to identify the distinguishing features of the cardiac components. Clin. Anat. 33:394-404, 2020. © 2019 Wiley Periodicals, Inc.

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Congenital heart defects (CHD) represent the most frequent type of the heart disease in childhood, with incidence up to 1 % of all live-born children. Despite the improving echocardiographic diagnostics, part of CHD remains undiagnosed and can manifest in the later age or may be the cause of the early abortion. On the other hand, some foetuses with prenatally diagnosed severe CHD may be recommended to interruption. Therefore, each pathologist can encounter a malformed heart at the autopsy. Despite the current quality of the echocardiography, the macroscopic assessment of the heart by the pathologist is still considered the best method for evaluation of the structural heart disease. Knowledge of the basic pathologic anatomy thus remains an important prerequisite for adequately performed paediatric autopsy.

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