Efficacy of aprepitant for refractory pruritus in patients with epidermolysis bullosa and atopic dermatitis: A retrospective study.

INTRODUCTION: At a single-center pediatric hospital, the neurokinin-1 receptor antagonist aprepitant was used to treat refractory pruritus in epidermolysis bullosa (EB) and atopic dermatitis (AD). METHODS: Thirty-seven patients were included (24 EB patients, 13 AD patients), ages 10 months to 37 years. RESULTS: 58% (14/24) of patients with EB and 85% (11/13) of patients with AD reported aprepitant was effective in decreasing their pruritus, with age-related differences in efficacy observed in EB patients, and access to the medication by insurance denial or availability of the drug as a barrier to use. CONCLUSIONS: Aprepitant shows promise in controlling refractory pruritus in pediatric EB and AD patients and deserves further study.

Integrated Proteomics Analysis of Baseline Protein Expression in Pig Tissues.

The availability of an increasingly large amount of public proteomics data sets presents an opportunity for performing combined analyses to generate comprehensive organism-wide protein expression maps across different organisms and biological conditions. Sus scrofa, a domestic pig, is a model organism relevant for food production and for human biomedical research. Here, we reanalyzed 14 public proteomics data sets from the PRIDE database coming from pig tissues to assess baseline (without any biological perturbation) protein abundance in 14 organs, encompassing a total of 20 healthy tissues from 128 samples. The analysis involved the quantification of protein abundance in 599 mass spectrometry runs. We compared protein expression patterns among different pig organs and examined the distribution of proteins across these organs. Then, we studied how protein abundances were compared across different data sets and studied the tissue specificity of the detected proteins. Of particular interest, we conducted a comparative analysis of protein expression between pig and human tissues, revealing a high degree of correlation in protein expression among orthologs, particularly in brain, kidney, heart, and liver samples. We have integrated the protein expression results into the Expression Atlas resource for easy access and visualization of the protein expression data individually or alongside gene expression data.

Attenuation of DNA base oxidation in post-surgery colorectal stage III patients at subsequent follow-ups.

DNA damage caused by oxidative reactions plays a crucial role in the pathogenesis of colorectal cancer (CRC). In a previous cross-sectional study, CRC patients diagnosed with regional disease (stage III) exhibited a higher level of DNA base oxidation in peripheral blood mononuclear cells (PBMCs) 2-9 months post-surgery compared to those with localized disease (stage I-II). To further explore this observation over time, the present study aimed to investigate DNA base oxidation in CRC patients with localized versus regional disease 6 and 12 months after the initial measurements. The present study included patients enrolled in the randomized controlled trial Norwegian Dietary Guidelines and Colorectal Cancer Survival (CRC-NORDIET). The standard comet assay, modified with the lesion-specific enzyme formamidopyrimidine DNA glycosylase (Fpg), was applied to measure DNA base oxidation in PBMCs at the 6- and 12-month follow-ups. Of the 255 patients assessed at baseline, 156 were included at the 6-month follow-up, with 89 of these patients included in the 12-month follow-up. In contrast to our observation at baseline, there were no significant differences in the levels of DNA base oxidation between patients diagnosed with localized disease and those with regional involvement at the 6- and 12-month follow-up visits (P = 0.81 and P = 0.09, respectively). Patients with stage III disease exhibited a significant decrease in the levels of DNA base oxidation from baseline to 6 months (P < 0.01) and baseline to 12 months (P = 0.03), but no significant difference from 6 to 12 months (P = 0.80). In conclusion, the initially elevated levels of DNA base oxidation in PBMCs, observed 2-9 months post-surgery in patients diagnosed with regional disease (stage III), subsequently decreased to levels comparable to patients with localized disease (stage I-II) at the 6- and 12-month follow-ups.

Stable Lateral Compression Pelvic Ring Injury Requiring Operative Treatment due to Bladder Impingement: A Case Report.

CASE: A 25-year-old man sustained a stable lateral compression Type I (LC I) pelvic ring injury upon missing the landing of a downhill ski jump. He presented with painful voiding from a displaced bony fragment, partially impaling the bladder wall. With operative fixation of the fracture and urologic co-management, the patient had excellent outcomes at 1-year follow-up. CONCLUSION: We describe a rare urologic injury in the setting of an LC I pelvic ring injury. In the setting of an otherwise stable pelvic ring injury, careful review of imaging, detailed clinical history, and physical examination remain critical to optimizing patient outcomes.

Biomechanical analysis of a trans-discal, multi-level stabilization screw (MLSS) at the upper instrumented vertebra (UIV) of long posterior thoracolumbar instrumentations.

PURPOSE: To evaluate proximal junctional biomechanics of a MLSS relative to traditional pedicle screw fixation at the proximal extent of T10-pelvis posterior instrumentation constructs (T10-p PSF). METHODS: A previously validated three-dimensional osseoligamentous spinopelvic finite element (FE) model was used to compare proximal junctional range-of-motion (ROM), vertebral body stresses, and discal biomechanics between two groups: (1) T10-p with a T10-11 MLSS ("T10-11 MLSS") and (2) T10-p with a traditional T10 pedicle screw ("Traditional T10-PS"). RESULTS: The T10-11 MLSS had a 5% decrease in T9 cortical bone stress compared to Traditional T10-PS. Conversely, the T10 and T11 bone stresses increased by 46% and 98%, respectively, with T10-11 MLSS compared to Traditional T10-PS. Annular stresses and intradiscal pressures (IDP) were similar at T9-T10 between constructs. At the T10-11 disc, T10-11 MLSS decreased annular stresses by 29% and IDP by 48% compared to Traditional T10-PS. Adjacent ROM (T8-9 & T9-10) were similar between T10-11 MLSS and Traditional T10-PS. T10-11 MLSS had 39% greater ROM at T10-11 and 23% less ROM at T11-12 compared to Traditional T10-PS. CONCLUSIONS: In this FE analysis, a T10-11 MLSS at the proximal extent of T10-pelvis posterior instrumentation resulted in increased T10 and T11 cortical bone stresses, decreased discal annular stress and IDP and increased ROM at T10-11, and no change in ROM at the adjacent level. Given the complex and multifactorial nature of proximal junctional kyphosis, these results require additional biomechanical and clinical evaluations to determine the clinical utility of MLSS on the proximal junctions of thoracolumbar posterior instrumented fusions.

Mechanism of Knee Injuries in the National Basketball Association: A Video-Based Analysis.

Background: To characterize the mechanism of knee injuries among NBA players during the 2010-2020 seasons using video-based analysis. Methods: An injury database of NBA players was queried for knee injuries from the 2006-07 to 2020-21 seasons and cross-referenced with NBA injury reports. Youtube.com was searched to identify available injury footage. The mechanism of knee injury during play was analyzed by three independent reviewers. Non-mechanistic data related to the injury was gathered from news reports and official NBA websites. Results: A total of 2,868 knee injuries occurred in NBA players from 2010 to 2020 seasons; 121 had high quality videos for analysis. The most common mechanism of injury was knee flexion in valgus with internal rotation (27.3%, p < 0.001), which was associated with injury to the ACL (55.2%, p=0.0001). Injuries occurred most often with control of the ball (62.8%, p=0.0064), while on offense (73.6%, p=0.0001), and without contact (71.1%, p=0.0001). A 28.1% incidence of re-injury was observed in the first 3-year period, and 43.8% of knee injuries required surgery. The average number of games missed due to injury requiring surgery was 55.1 games compared to 8.5 games in those treated nonoperatively (p < 0.0001). Conclusion: Understanding mechanisms of knee injury may guide preventative strategies and injury management programs in NBA players. Video-based analysis reveals the situational characteristics and mechanisms of knee injuries, but further studies are needed to develop injury prevention programs, efficacy of prevention strategies, and rehabilitation to minimize games missed from these injuries.

Effect of a personalized intensive dietary intervention on base excision repair (BER) in colorectal cancer patients: Results from a randomized controlled trial.

DNA repair is essential to maintain genomic integrity and may affect colorectal cancer (CRC) patients' risk of secondary cancers, treatment efficiency, and susceptibility to various comorbidities. Bioactive compounds identified in plant foods have the potential to modulate DNA repair mechanisms, but there is limited evidence of how dietary factors may affect DNA repair activity in CRC patients in remission after surgery. The aim of this study was to investigate the effect of a 6-month personalized intensive dietary intervention on DNA repair activity in post-surgery CRC patients (stage I-III). The present study included patients from the randomized controlled trial CRC-NORDIET, enrolled 2-9 months after surgery. The intervention group received an intensive dietary intervention emphasizing a prudent diet with specific plant-based foods suggested to dampen inflammation and oxidative stress, while the control group received only standard care advice. The comet-based in vitro repair assay was applied to assess DNA repair activity, specifically base excision repair (BER), in peripheral blood mononuclear cells (PBMCs). Statistical analyses were conducted using gamma generalized linear mixed models (Gamma GLMM). A total of 138 CRC patients were included, 72 from the intervention group and 66 from the control group. The BER activity in the intervention group did not change significantly compared to the control group. Our findings revealed a substantial range in both inter- and intra-individual levels of BER. In conclusion, the results do not support an effect of dietary intervention on BER activity in post-surgery CRC patients during a 6-month intervention period.

The Comet Assay as a Tool in Human Biomonitoring Studies of Environmental and Occupational Exposure to Chemicals-A Systematic Scoping Review.

Biomonitoring of human populations exposed to chemical substances that can act as potential mutagens or carcinogens, may enable the detection of damage and early disease prevention. In recent years, the comet assay has become an important tool for assessing DNA damage, both in environmental and occupational exposure contexts. To evidence the role of the comet assay in human biomonitoring, we have analysed original research studies of environmental or occupational exposure that used the comet assay in their assessments, following the PRISMA-ScR method (preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews). Groups of chemicals were designated according to a broad classification, and the results obtained from over 300 original studies (n = 123 on air pollutants, n = 14 on anaesthetics, n = 18 on antineoplastic drugs, n = 57 on heavy metals, n = 59 on pesticides, and n = 49 on solvents) showed overall higher values of DNA strand breaks in the exposed subjects in comparison with the unexposed. In summary, our systematic scoping review strengthens the relevance of the use of the comet assay in assessing DNA damage in human biomonitoring studies.

Deep learning model shows promise for detecting and grading sesamoiditis in horse radiographs.

OBJECTIVE: The objective of this study was to develop a robust machine-learning approach for efficient detection and grading of sesamoiditis in horses using radiographs, specifically in data-limited conditions. SAMPLE: A dataset of 255 dorsolateral-palmaromedial oblique (DLPMO) and dorsomedial-palmarolateral oblique (DMPLO) equine radiographs were retrospectively acquired from Hagyard Equine Medical Institute. These images were anonymized and classified into 3 categories of sesamoiditis severity (normal, mild, and moderate). METHODS: This study was conducted from February 1, 2023, to August 31, 2023. Two RetinaNet models were used in a cascaded manner, with a self-attention module incorporated into the second RetinaNet's classification subnetwork. The first RetinaNet localized the sesamoid bone in the radiographs, while the second RetinaNet graded the severity of sesamoiditis based on the localized region. Model performance was evaluated using the confusion matrix and average precision (AP). RESULTS: The proposed model demonstrated a promising classification performance with 92.7% accuracy, surpassing the base RetinaNet model. It achieved a mean average precision (mAP) of 81.8%, indicating superior object detection ability. Notably, performance metrics for each severity category showed significant improvement. CLINICAL RELEVANCE: The proposed deep learning-based method can accurately localize the position of sesamoid bones and grade the severity of sesamoiditis on equine radiographs, providing corresponding confidence scores. This approach has the potential to be deployed in a clinical environment, improving the diagnostic interpretation of metacarpophalangeal (fetlock) joint radiographs in horses. Furthermore, by expanding the training dataset, the model may learn to assist in the diagnosis of pathologies in other skeletal regions of the horse.

Change in cyclone disaster vulnerability and response in coastal Bangladesh.

The number of deaths owing to tropical cyclones in Bangladesh has significantly reduced. Category 4 Cyclone Gorky in 1991 and Sidr in 2007 caused 147,000 and 4,500 deaths respectively, whereas Category 1 Cyclone Mora in 2017 resulted in six. Face-to-face interviews with 362 residents, participant observation, and focus-group discussions answer a research question about how change in coastal areas has contributed to this outcome. The study considered institutional approaches of disaster risk management through legal frameworks, administrative arrangements, cyclone preparedness activities, cyclone detection and early warning dissemination, construction of shelter centres, strengthening of various types of coastal embankments, paved roads, and pre-cyclone evacuation. The findings indicate significant improvement in house structures and design, income levels and diversification, education, awareness, individual capacity, poverty reduction, and lowering dependency on agriculture-based earning. Furthermore, the availability of mobile telephones, radio, television, and social media platforms enhanced social connectivity and greater gender equality and empowerment helped to facilitate disaster preparedness, evacuation, and response.

Abdominal lymphocele following multi-level anterior lumbar interbody fusion (ALIF) managed with a laparoscopic peritoneal window: case report and review of the literature.

PURPOSE: Lymphocele formation following anterior lumbar interbody fusion (ALIF) is not common, but it can pose diagnostic and treatment challenges. The purpose of this case is to report for the first time the treatment of a postoperative lymphocele following a multi-level ALIF using a peritoneal window made through a minimally invasive laparoscopic approach. METHODS: Case report. RESULTS: A 74-year-old male with a history of prostatectomy and pelvic radiation underwent a staged L3-S1 ALIF (left paramedian approach) and T10-pelvis posterior instrumented with L1-5 decompression/posterior column osteotomies for degenerative scoliosis and neurogenic claudication. Three weeks after surgery, swelling of the left abdomen and entire left leg was reported. Computed tomography of the abdomen/pelvis demonstrated a large (19.2 × 12.0 × 15.4 cm) retroperitoneal fluid collection with compression of the left ureter and left common iliac vein. Fluid analysis (80% lymphocytes) was consistent with a lymphocele. Percutaneous drainage for 4 days was ineffective at clearing the lymphocele. For more definitive management, the patient underwent an uncomplicated laparoscopic creation of a peritoneal window to allow passive drainage of lymphatic fluid into the abdomen. Three years after surgery, he had no back or leg pain, had achieved spinal union, and had no abdominal swelling or left leg swelling. Advanced imaging also confirmed resolution of the lymphocele. CONCLUSIONS: In this case report, creation of a peritoneal window minimally invasively via a laparoscope allowing passive drainage of lymphatic fluid into the abdomen was safe and effective for management of an abdominal lymphocele following a multi-level ALIF.

DNA base oxidation in relation to TNM stages and chemotherapy treatment in colorectal cancer patients 2-9 months post-surgery.

Accumulation of DNA damage is a critical feature of genomic instability, which is a hallmark of various cancers. The enzyme-modified comet assay is a recognized method to detect specific DNA lesions at the level of individual cells. In this cross-sectional investigation, we explore possible links between clinicopathological and treatment related factors, nutritional status, physical activity and function, and DNA damage in a cohort of colorectal cancer (CRC) patients with non-metastatic disease. Levels of DNA damage in peripheral mononuclear blood cells (PBMCs) assessed 2-9 months post-surgery, were compared across tumour stage (localized (stage I-II) vs. regional (stage III) disease), localization (colon vs. rectosigmoid/rectum cancer), and adjuvant chemotherapy usage, with the last dosage administrated 2-191 days prior to sampling. Associations between DNA damage and indicators of nutritional status, physical activity and function were also explored. In PBMCs, DNA base oxidation was higher in patients diagnosed with regional compared with localized tumours (P = 0.03), but no difference was seen for DNA strand breaks (P > 0.05). Number of days since last chemotherapy dosage was negatively associated with DNA base oxidation (P < 0.01), and patients recently receiving chemotherapy (<15 days before blood collection) had higher levels of DNA base oxidation than those not receiving chemotherapy (P = 0.03). In the chemotherapy group, higher fat mass (in kg and %) as well as lower physical activity were associated with greater DNA base oxidation (P < 0.05). In conclusion, DNA base oxidation measured with the enzyme-modified comet assay varies according to tumour and lifestyle related factors in CRC patients treated for non-metastatic disease.

Unraveling the Genetic Threads of History: mtDNA HVS-I Analysis Reveals the Ancient Past of the Aburra Valley.

This article presents a comprehensive genetic study focused on pre-Hispanic individuals who inhabited the Aburrá Valley in Antioquia, Colombia, between the tenth and seventeenth centuries AD. Employing a genetic approach, the study analyzed maternal lineages using DNA samples obtained from skeletal remains. The results illuminate a remarkable degree of biological diversity within these populations and provide insights into their genetic connections with other ancient and indigenous groups across the American continent. The findings strongly support the widely accepted hypothesis that the migration of the first American settlers occurred through Beringia, a land bridge connecting Siberia to North America during the last Ice Age. Subsequently, these early settlers journeyed southward, crossing the North American ice cap. Of particular note, the study unveils the presence of ancestral lineages from Asian populations, which played a pivotal role in populating the Americas. The implications of these results extend beyond delineating migratory routes and settlement patterns of ancient populations. They also enrich our understanding of the genetic diversity inherent in indigenous populations of the region. By revealing the genetic heritage of pre-Hispanic individuals from the Aburrá Valley, this study offers valuable insights into the history of human migration and settlement in the Americas. Furthermore, it enhances our comprehension of the intricate genetic tapestry that characterizes indigenous communities in the area.

High Mitochondrial Haplotype Diversity Found in Three Pre-Hispanic Groups from Colombia.

The analysis of mitochondrial DNA (mtDNA) hypervariable region (HVR) sequence data from ancient human remains provides valuable insights into the genetic structure and population dynamics of ancient populations. mtDNA is particularly useful in studying ancient populations, because it is maternally inherited and has a higher mutation rate compared to nuclear DNA. To determine the genetic structure of three Colombian pre-Hispanic populations and compare them with current populations, we determined the haplotypes from human bone remains by sequencing several mitochondrial DNA segments. A wide variety of mitochondrial polymorphisms were obtained from 33 samples. Our results support a high population heterogeneity among pre-Hispanic populations in Colombia.

Performance of Orthopaedic Shoulder and Elbow Surgeons on a Biostatistical Knowledge Examination.

Background: The objective of this study is to evaluate the biostatistical interpretation abilities of fellowship trained orthopaedic surgeons. Methods: A cross-sectional survey was administered to orthopaedic surgeon members of the American Shoulder and Elbow Surgeons (ASES), assessing orthopaedic surgeon attitudes towards biostatistics, confidence in understanding biostatistics, and ability to interpret biostatistical measures on a multiple-choice test. Results: A 4.5% response rate was achieved with 55 complete survey responses. The mean percent correct was 55.2%. Higher knowledge test scores were associated with younger age and fewer years since board exam completion (p ≤ 0.001). Greater average number of publications per year correlated with superior statistical interpretation (p=0.009). Respondents with higher self-reported confidence were more likely to accurately interpret results (p ≤ 0.017). Of the respondents, 93% reported frequently using statistics to form medical opinions, 98% answered that statistical competency is important in the practice of orthopaedic surgery, and 80% were eager to continue learning biostatistics. Conclusions: It is concerning that fellowship-trained shoulder and elbow surgeons, many of whom frequently publish or are reviewing scientific literature for publication, are scoring 55.2% correctly on average on this biostatistical knowledge examination. Surgeons that are further from formal statistical knowledge training are more likely to have lower biostatistical knowledge test scores. Respondents who published at the highest rate were associated with higher scores. Continuing medical education in biostatistics may be beneficial for maintaining statistical knowledge utilised in the current literature.

IGHV allele similarity clustering improves genotype inference from adaptive immune receptor repertoire sequencing data.

In adaptive immune receptor repertoire analysis, determining the germline variable (V) allele associated with each T- and B-cell receptor sequence is a crucial step. This process is highly impacted by allele annotations. Aligning sequences, assigning them to specific germline alleles, and inferring individual genotypes are challenging when the repertoire is highly mutated, or sequence reads do not cover the whole V region. Here, we propose an alternative naming scheme for the V alleles, as well as a novel method to infer individual genotypes. We demonstrate the strengths of the two by comparing their outcomes to other genotype inference methods. We validate the genotype approach with independent genomic long-read data. The naming scheme is compatible with current annotation tools and pipelines. Analysis results can be converted from the proposed naming scheme to the nomenclature determined by the International Union of Immunological Societies (IUIS). Both the naming scheme and the genotype procedure are implemented in a freely available R package (PIgLET https://bitbucket.org/yaarilab/piglet). To allow researchers to further explore the approach on real data and to adapt it for their uses, we also created an interactive website (https://yaarilab.github.io/IGHV_reference_book).

DNA strand break levels in cryopreserved mononuclear blood cell lines measured by the alkaline comet assay: results from the hCOMET ring trial.

The comet assay is widely used in biomonitoring studies for the analysis of DNA damage in leukocytes and peripheral blood mononuclear cells. Rather than processing blood samples directly, it can be desirable to cryopreserve whole blood or isolated cells for later analysis by the comet assay. However, this creates concern about artificial accumulation of DNA damage during cryopreservation. In this study, 10 laboratories used standardized cryopreservation and thawing procedures of monocytic (THP-1) or lymphocytic (TK6) cells. Samples were cryopreserved in small aliquots in 50% foetal bovine serum, 40% cell culture medium, and 10% dimethyl sulphoxide. Subsequently, cryopreserved samples were analysed by the standard comet assay on three occasions over a 3-year period. Levels of DNA strand breaks in THP-1 cells were increased (four laboratories), unaltered (four laboratories), or decreased (two laboratories) by long-term storage. Pooled analysis indicates only a modest positive association between storage time and levels of DNA strand breaks in THP-1 cells (0.37% Tail DNA per year, 95% confidence interval: -0.05, 0.78). In contrast, DNA strand break levels were not increased by cryopreservation in TK6 cells. There was inter-laboratory variation in levels of DNA strand breaks in THP-1 cells (SD = 3.7% Tail DNA) and TK6 reference sample cells (SD = 9.4% Tail DNA), whereas the intra-laboratory residual variation was substantially smaller (i.e. SD = 0.4%-2.2% Tail DNA in laboratories with the smallest and largest variation). In conclusion, the study shows that accumulation of DNA strand breaks in cryopreserved mononuclear blood cell lines is not a matter of concern.