Intrapatient variation in PD-L1 expression and tumor mutational burden and the impact on outcomes to immune checkpoint inhibitor therapy in patients with non-small cell lung cancer.

BACKGROUND: PD-L1 tumor proportion score (TPS) and tumor mutational burden (TMB) are key predictive biomarkers for immune checkpoint inhibitors (ICI) efficacy in non-small cell lung cancer (NSCLC). Data on their variation across multiple samples are limited. METHODS: Patients with NSCLC and multiple PD-L1 TPS and/or TMB assessments were included. Clinicopathologic and genomic data were analyzed according to PD-L1 and TMB variation. RESULTS: In total, 402 PD-L1 sample pairs and 413 TMB sample pairs were included. Concordance between pairs was moderate for PD-L1 (ρ=0.53, P<0.0001) and high for TMB (ρ=0.80, P<0.0001). Shorter time between biopsies correlated with higher concordance in PD-L1, but not in TMB. Major increases (ΔTPS≥+50%) and decreases (ΔTPS≤-50%) in PD-L1 were observed in 9.7% and 8.0% of cases, respectively. PD-L1, but not TMB, decreased with intervening ICI (P=0.02). Acquired copy number loss of CD274, PDCD1LG2, and JAK2 were associated with major decrease in PD-L1 (q<0.05). Among patients with multiple PD-L1 assessments before ICI, cases where all samples had a PD-L1 ≥1%, compared to cases with at least one sample with PD-L1 <1% and another with PD-L1 ≥1%, achieved improved objective response rate and progression-free survival (PFS). Among patients with at least one PD-L1 <1% and one ≥1% before ICI, cases where the most proximal sample was PD-L1 ≥1% had longer median PFS compared to cases where the most proximal PD-L1 was <1%. Among patients with multiple TMB assessments before ICI, patients with a TMB ≥10 mut/Mb based on the most recent assessment, as compared to those with a TMB <10 mut/Mb, achieved improved PFS and OS to ICI; instead, no differences were observed when patients were categorized using the oldest TMB assessment. CONCLUSION: Despite intrapatient concordance in PD-L1 and TMB, variation in these biomarkers can influence ICI outcomes, warranting consideration for reassessment prior to ICI initiation when feasible.

Faecal contamination in China: Trends, sources, and driving mechanisms.

Faecal contamination of surface waters is a global public health and economic burden. Here, we constructed a 30-year dataset to analyse the spatiotemporal trends and driving mechanisms of faecal coliforms (FCs) in China. We found that previous national policies to reduce water pollution have significantly improved the quality of surface water and, correspondingly, faecal contamination. However, the downward trend in FC levels has been more gradual than that for physico-chemical pollutants, and this trend may be exaggerated. Our results show that the driving mechanisms of faecal pollution were seasonal and complex. During the dry season, forests and grasslands were the source landscapes that exacerbated faecal pollution; during the wet season, urbanisation dominated, highlighting China's poorly designed drainage systems. Our projections revealed that faecal contamination will continue to worsen from 2022 to 2035, highlighting the need for pollution control. In the future, faecal indicators should be included in routine monitoring, evaluation, and assessment at the national level. Moreover, coordinated design of forest, grassland, and wetland landscapes is recommended for faecal pollution control at the regional level, whereas stormwater-related source control needs to be further strengthened at the urban level.

Two Palatal Roots in Maxillary First Molar, a Rare Entity: Report of Two Cases.

An in-depth understanding of the anatomical variations of maxillary molars is essential for endodontic success. Unlike the maxillary second molars, the presence of a second palatal root is uncommon in the first maxillary molar. This case report describes two cases of non-surgical management of maxillary molars with extra palatal roots. Careful clinical examination, knowledge of the internal anatomy, and the use of advanced radiographic modalities like cone beam computed tomography (CBCT) can reveal the presence of variations in the internal and external anatomy of any tooth. Therefore, for nonsurgical as well as surgical management clinicians should always watch out for any deviations in a tooth and utilize all the available tools to diagnose and manage them successfully.

Circadian variations influence anxiety-related behaviour, olfaction, and hedonic response in male Sprague-Dawley rats.

INTRODUCTION: Despite the acknowledged impact of circadian rhythms on various aspects of life, behavioural tests with laboratory animals often overlook alignment with their natural activity patterns. This study aims to evaluate the influence of circadian variations on the results, validity, and reliability of different behavioural tests in rats. METHODS: Three behavioural tests, the Light-Dark Box Test (LDB), assessing anxiety-related behaviour and locomotor activity; the Buried Pellet Test (BPT), revealing olfactory abilities and motivation issues; and the Sucrose Preference Test (SPT), studying the anhedonic response, were employed to encompass multiple daytime-dependent behavioural aspects in male Sprague-Dawley rats. RESULTS: Our findings underscore distinct circadian effects on locomotor activity, exploratory behaviour, olfactory acuity, motivation, and hedonic response. Notably, anxious behaviour remained unaffected by daytime conditions. Furthermore, decreased data variance was found to be correlated with conducting behavioural tests during the subjects' active phase. DISCUSSION: This study demonstrates extensive circadian influences on nearly all parameters investigated, coupled with a significant reduction in data variability during the active phase. Emphasising the importance of aligning experimental timing with rats' natural activity patterns, our results suggest that conducting tests during the active phase of the animals not only refines test sensitivity , reduces stress, and provides more representative data, but also contributes to ethical animal research (3 R) and improves test relevance. This, in turn, enhances the reliability and validity of experimental outcomes in behavioural research and promotes animal welfare.

Congenital three generation wide familial non-syndromic polydactyly.

Polydactyly is typically observed as isolated and sporadic occurrences, although familial cases do exist, albeit with lower frequency, manifesting in various inheritance patterns. In around 30% of polydactyly cases, there exists a familial history, suggesting the probable involvement of a single gene. Given its potential for hereditary transmission, thorough investigation of the patients' parents, first-degree relatives, grandparents, and even great-grandparents for similar disorders becomes imperative. In our clinic, we conducted an analysis focusing on patients presenting with foot polydactyly, along with occurrences of polydactyly among their first- and second-degree relatives spanning two to three generations of family history. The study encompassed three patients and their respective families, including a pair of siblings. We speculate that the inheritance type in our cases was autosomal dominant. Among our patients, one presented with central polydactyly, while the remaining patients and all familial cases displayed postaxial polydactyly. In terms of morphologic classification, one patient had a Y-shaped metatarsal, another had a T-shaped metatarsal, and the third patient exhibited a duplicated ray-shaped anomaly. In our review of the literature, we haven't come across a case spanning three generations like the ones we encountered. Additionally, the presence of a transverse accessory extensor tendon between both extensor tendons in cases with T- and Y-shaped metatarsals intrigued us from an anatomical perspective. Our goal is to present these rare cases of congenital familial polydactyly spanning three generations, highlighting the anatomical variations observed and aiming to contribute to the existing body of literature on the subject.

A Comparative Analysis of the Efficacy of Local Anesthetics and Systemic Anesthetics in the Red-Headed Versus Non-Red-Headed Patient Population: A Comprehensive Review.

Researchers have found that individuals with red hair often require higher doses of anesthetic medications to achieve the same level of pain relief or sedation compared to people with other hair colors. This review investigates the effects of local and systemic anesthetics in individuals with red hair compared to the general population. Focusing on both local and systemic anesthesia, this research aims to elucidate any distinctive responses or complications among the red-haired demographic. Utilizing a systematic review approach, we analyzed a wide array of previous research papers published over the last two decades to gather relevant data. Our findings suggest that people with red hair may exhibit variations in their response to both local and systemic anesthesia compared to non-red-haired individuals, indicating the necessity for tailored anesthetic approaches in clinical settings. Previous studies have found that individuals with red hair, as well as those with the corresponding melanocortin-1 receptor (MC1R) mutations, exhibit a greater resistance to the effects of systemic and local anesthetics. This review provides valuable insights that could help healthcare professionals optimize anesthetic management and improve patient outcomes, particularly for those with red hair.

Higher tumor mutational burden is associated with inferior outcomes among pediatric patients with neuroblastoma.

INTRODUCTION: Neuroblastoma is a pediatric malignancy with heterogeneous clinical outcomes. Our aim was to identify prognostic genetic markers for patients with neuroblastoma, who were treated with the Taiwan Pediatric Oncology Group (TPOG) neuroblastoma N2002 protocol, to improve risk stratification and inform treatment. METHODS: Our analysis was based on 53 primary neuroblastoma specimens, diagnosed pre-chemotherapy, and 11 paired tumor relapse specimens. Deep sequencing of 113 target genes was performed using a custom panel. Multiplex ligation-dependent probe amplification was performed to identify clinical outcomes related to copy-number variations. RESULTS: We identified 128 variations associated with survival, with the number of variations being higher in the relapse than that in the diagnostic specimen (p = .03). The risk of event and mortality was higher among patients with a tumor mutational burden ≥10 than that in patients with a lower burden (p < .0001). Multivariate analysis identified tumor mutational burden, MYCN amplification, and chromosome 3p deletion as significant prognostic factors, independent of age at diagnosis, sex, and tumor stage. The 5-year event-free survival and overall survival rate was lower among patients with high tumor burden than in patients with low tumor burden. Furthermore, there was no survival of patients with an ALK F1147L variation at 5 years after diagnosis. CONCLUSIONS: Genome sequencing to determine the tumor mutational burden and ALK variations can improve the risk classification of neuroblastoma and inform treatment.

The Efficacy of Local Autologous Platelet-Rich Plasma Prepared by Single and Double Spin Methods in the Treatment of Chronic Ulcer.

BACKGROUND: Chronic nonhealing ulcers present significant challenges in diabetic, dermatological, and surgical patients. Platelet-rich plasma (PRP), enriched with bioactive factors, offers promise for wound healing enhancement. This study evaluates PRP's efficacy, prepared via single and double spin methods in nonhealing chronic ulcers. METHODS:  Twenty-two patients aged 18-65 years participated and 100 mL of blood was drawn into citrate phosphate dextrose adenine (CPDA) bags with all aseptic precautions. PRP was prepared by single and double spin methods. Patient serum and 10% calcium gluconate were added to fibrin gel. PRP was injected around the ulcer and then dressed. Dressings were changed on the fifth, 15th, and 20th days with PRP. Evaluation occurred on day 30 using surface area and volume assessments by both methods. RESULTS: The single spin PRP group and double spin PRP group had 11 patients each with hemoglobin range of 10.79±1.88 to 12.63±2.22 g/dL. Initial lesions (16.27 cm²) significantly reduced to 14.76 cm² after double spin PRP sessions (p=0.005) and Initial lesions (9.87 cm²) significantly reduced to 7.65 cm² after single spin PRP sessions (p=0.005). Platelet count differences between whole blood and PRP were significant (p<0.05). CONCLUSIONS: The single spin PRP method exhibited considerable improvements in healing parameters, showcasing its potential for chronic ulcer management.

eDNA-based survey of the marine vertebrate biodiversity off the west coast of Guadeloupe (French West Indies).

Background: In the marine environment, knowledge of biodiversity remains incomplete for many taxa, requiring assessments to understand and monitor biodiversity loss. Environmental DNA (eDNA) metabarcoding is a powerful tool for monitoring marine biodiversity, as it enables several taxa to be characterised simultaneously in a single sample. However, the data generated by environmental DNA metabarcoding are often not easily reusable. Implementing FAIR principles and standards for eDNA-derived data can facilitate data-sharing within the scientific community. New information: This study focuses on the detection of marine vertebrate biodiversity using eDNA metabarcoding on the leeward coast of Guadeloupe, a known hotspot for marine biodiversity in the French West Indies. Occurrences and DNA-derived data are shared here using DarwinCore standards combined with MIMARKS standards.

Long-Read Structural and Epigenetic Profiling of a Kidney Tumor-Matched Sample with Nanopore Sequencing and Optical Genome Mapping.

Carcinogenesis often involves significant alterations in the cancer genome architecture, marked by large structural and copy number variations (SVs and CNVs) that are difficult to capture with short-read sequencing. Traditionally, cytogenetic techniques are applied to detect such aberrations, but they are limited in resolution and do not cover features smaller than several hundred kilobases. Optical genome mapping and nanopore sequencing are attractive technologies that bridge this resolution gap and offer enhanced performance for cytogenetic applications. These methods profile native, individual DNA molecules, thus capturing epigenetic information. We applied both techniques to characterize a clear cell renal cell carcinoma (ccRCC) tumor's structural and copy number landscape, highlighting the relative strengths of each method in the context of variant size and average read length. Additionally, we assessed their utility for methylome and hydroxymethylome profiling, emphasizing differences in epigenetic analysis applicability.

Comparison of the diagnostic significance of cerebrospinal fluid metagenomic next-generation sequencing copy number variation analysis and cytology in leptomeningeal malignancy.

BACKGROUND: Diagnosis and monitoring of leptomeningeal malignancy remain challenging, and are usually based on neurological, radiological, cerebrospinal fluid (CSF) and pathological findings. This study aimed to investigate the diagnostic performance of CSF metagenomic next-generation sequencing (mNGS) and chromosome copy number variations (CNVs) analysis in the detection of leptomeningeal malignancy. METHODS: Of the 51 patients included in the study, 34 patients were diagnosed with leptomeningeal malignancies, and 17 patients were diagnosed with central nervous system (CNS) inflammatory diseases. The Sayk's spontaneous cell sedimentation technique was employed for CSF cytology. And a well-designed approach utilizing the CSF mNGS-CNVs technique was explored for early diagnosis of leptomeningeal malignancy. RESULTS: In the tumor group, 28 patients were positive for CSF cytology, and 24 patients were positive for CSF mNGS-CNVs. Sensitivity and specificity of CSF cytology were 82.35% (95% CI: 66.83-92.61%) and 94.12% (95% CI: 69.24-99.69%). In comparison, sensitivity and specificity of CSF mNGS-CNV were 70.59% (95% CI: 52.33-84.29%) and 100% (95% CI: 77.08-100%). There was no significant difference in diagnostic consistency between CSF cytology and mNGS-CNVs (p = 0.18, kappa = 0.650). CONCLUSIONS: CSF mNGS-CNVs tend to have higher specificity compared with traditional cytology and can be used as a complementary diagnostic method for patients with leptomeningeal malignancies.

The quadratus femoris muscle anatomy: Do we know everything?

INTRODUCTION: The purpose of this study was to characterize the morphological variations in the quadratus femoris muscle (QF) and to create an anatomical classification that could be used in the planning of surgical procedures in this area, radiological imaging, and rehabilitation. MATERIALS AND METHODS: Ninety-two lower limbs from 46 cadavers, fixed in 10 % formalin solution, were examined. RESULTS: The QF muscle was present in all specimens. According to morphology, the QF muscle was classified into three types. The most common type was Type I, characterized by one muscular belly (78.3 %), while the second most common type was Type II, characterized by two bellies, was observed in 17.4 % of cases. The rarest type was Type III. It was characterized by three bellies and was found in 4.3 % of the cases. CONCLUSIONS: The current classification system on quadratus femoris morphological variability is novel. Morphological variants may contribute to clinical issues, such as the ischiofemoral impingement syndrome, that could arise from type I quadratus femoris. Hence, the current study may be applicated to planning surgical procedures, imaging, and rehabilitation.

Seasonal variations of organophosphate esters (OPEs) in atmospheric deposition, and their contribution to soil loading.

Organophosphate esters (OPEs) are ubiquitous in surface soil, and atmospheric deposition is considered to be the major pollution source. However, the research on the environmental transport behaviors of OPEs between atmospheric deposition and soil is very limited. In this study, we investigated the contamination levels and seasonal variations of OPEs in atmospheric deposition samples (n = 33) collected from an area of South China every month between February 2021 and January 2022, and evaluated the contribution of OPEs in atmospheric deposition to soil. The concentrations of ∑21target-OPEs ranged from 3670 to 18,600 ng/g dry weight (dw), with a mean of 8200 ng/g dw (median: 7600 ng/g dw). ∑21target-OPEs concentrations in all atmospheric deposition samples exhibited significant seasonal differences (p < 0.05) with higher concentrations observed in winter and lower concentrations in summer. Tris(2,4-di-tert-butylphenyl) phosphate (TDTBPP) was the most dominant target OPE in atmospheric deposition (4870 ng/g dw), and its seasonal variation trend was consistent with ∑21OPEs (p < 0.05). Simultaneously, in order to further explore the effect of atmospheric deposition on the levels of OPEs in soil of the study region, input fluxes and accumulation increments were estimated. Ten OPEs (including seven target OPEs and three suspect OPEs) exhibited high input flux means and accumulation increments, indicating that these compounds are prone to accumulate in soil via atmospheric deposition. It is noteworthy that the non-target phosphonate analyte bis(2,4-di-tert-butylphenyl) dibutyl ethane-1,2-diylbis(phosphonate) (BDTBPDEDBP) was detected at highest median concentration (8960 ng/g dw) in atmospheric deposition. Correspondingly, the average input flux and accumulation increment of BDTBPDEDBP were higher than those of all target and suspect OPEs. Collectively, this study quantifies the environmental transport behavior of OPEs between atmospheric deposition and soil, and provides new evidences for the fact that atmospheric deposition is the important pollution source of OPEs in soil.

Assessing the frequency and variability of accessory zygomatic sutures in dry skulls: clinical insights and potential implications.

PURPOSE: This study aimed to determine the presence and incidence of accessory sutures and bipartite zygomatic bone types, and their effects on population affinity and clinical significance. METHODS: We examined 120 dry skulls and 50 zygomatic bones to evaluate the presence, frequency, and location of accessory zygomatic sutures as well as subtypes of bipartite zygomatic bones. Morphometric analysis included measuring the total width and length of the zygomatic bone with accessory sutures (ASs), the total length of the AS, and the shortest distance between the AS and various anatomical landmarks. RESULTS: Bipartite zygomatic bone was observed in 14 of 120 dry skulls (11.6%) and 1 of 50 zygomatic bones (2%), indicating an overall incidence of 16 occurrences (8.82%). The ASs were predominantly located posterolaterally in 11 cases (six males, five females), anteromedially in two cases (one male, one female), superiorly in one case (male), and superolaterally in one case (male). Significant differences were noted in the distribution of the ASs (p < 0.001). Notably, a vertical inferior bipartite zygomatic type, which has not been reported in the literature, was identified. Correlations were observed between the various anatomical landmarks. Among females, the length of AS was significantly different (p = 0.038). Significant differences were also noted in the shortest distance between the AS and the zygomaticofacial foramen (ZFF) based on the body side (p = 0.034). CONCLUSIONS: Our study suggests that the bipartite zygomatic bone is not a common occurrence, indicating its significance as a morphological variation present in certain individuals. The type VII bipartite zygomatic bone exhibited the highest incidence rate, suggesting potential ethnic-specific differences in the prevalence of certain subtypes. The consistent pattern of suture distribution, along with the asymmetry and variability in suture patterns, emphasizes its potential clinical relevance.

Germline Co-deletion of CDKN2A and CDKN2B Genes in Pleomorphic Xanthoastrocytoma: Case Report.

BACKGROUND/AIM: Gliomas are highly heterogeneous malignancies originating from diverse cell types within the brain. Although their precise etiology is frequently unknown, risk factors, such as chemical exposure, radiation, and specific uncommon genetic disorders have been identified. Diagnosis typically entails imaging tests, such as magnetic resonance imaging and computed tomography, complemented by a biopsy for confirmation, which may be further validated through genetic testing. CASE REPORT: Next-generation sequencing technology revealed germline co-deletion deletion of cyclin-dependent kinase inhibitor 2 A and B genes (CDKN2A and CDKN2B) in a patient diagnosed with pleomorphic xanthoastrocytoma based on the tumor's molecular characteristics. Following this result, we performed focused genetic analysis with use of multiplex ligation-dependent probe amplification technology for the mother that revealed the same co-deletion. Moreover, due to the father's neuroendocrine pancreatic cancer, application of the NGS technology detected a pathogenic variant in the BRCA1-interacting helicase 1 (BRIP1) gene. Comprehensive multi-gene testing conducted within the familial context, marked by a varied spectrum of cancer type, revealed a constellation of genetic predispositions. CONCLUSION: This case study underscores the critical importance of molecular testing for tumor characterization and highlights the pivotal role of genetic testing in facilitating early intervention and screening for at-risk family members. Furthermore, the identification of germline co-deletions in cancer lays the foundation for the development of targeted therapeutic strategies aimed at restoring normal cellular regulation and improving patient management.

Water quality assessment in a large plateau lake in China from 2014 to 2021 with machine learning models: Implications for future water quality management.

Amid the global surge of eutrophication in lakes, investigating and analyzing water quality and trends of lakes becomes imperative for formulating effective lake management policies. Water quality index (WQI) is one of the most used tools to assess water quality by integrating data from multiple water quality parameters. In this study, we analyzed the spatio-temporal variations of 11 water quality parameters in one of the largest plateau lakes, Erhai Lake, based on surveys from January 2014 to December 2021. Leveraging machine learning models, we gauged the relative importance of different water quality parameters to the WQI and further utilized stepwise multiple linear regression to derive an optimal minimal water quality index (WQImin) that required the minimal number of water quality parameters without compromising the performance. Our results indicated that the water quality of Erhai Lake typically showed a trend towards improvement, as indicated by the positive Mann-Kendall test for WQI performance (Z = 2.89, p < 0.01). Among the five machine learning models, XGBoost emerged as the best performer (coefficient of determination R2 = 0.822, mean squared error = 3.430, and mean absolute error = 1.460). Among the 11 water quality parameters, only four (i.e., dissolved oxygen, ammonia nitrogen, total phosphorus, and total nitrogen) were needed for the optimal WQImin. The establishment of the WQImin helps reduce cost in future water quality monitoring in Erhai Lake, which may also serve as a valuable framework for efficient water quality monitoring in similar waters. In addition, the elucidation of spatio-temporal patterns and trends of Erhai Lake's water quality serves as a compass for authorities, offering insights to bolster lake management strategies in the future.

Seasonal dynamics of antibiotic resistance genes and mobile genetic elements in a subtropical coastal ecosystem: Implications for environmental health risks.

Antibiotic resistance poses a considerable global public health concern, leading to heightened rates of illness and mortality. However, the impact of seasonal variations and environmental factors on the health risks associated with antibiotic resistance genes (ARGs) and their assembly mechanisms is not fully understood. Based on metagenomic sequencing, this study investigated the antibiotic resistome, mobile genetic elements (MGEs), and microbiomes in a subtropical coastal ecosystem of the Beibu Gulf, China, over autumn and winter, and explored the factors influencing seasonal changes in ARG and MGE abundance and diversity. Results indicated that ARG abundance and diversity were higher in winter than in autumn, with beta-lactam and multidrug resistance genes being the most diverse and abundant, respectively. Similarly, MGE abundance and diversity increased in winter and were strongly correlated with ARGs. In contrast, more pronounced associations between microbial communities, especially archaea, and the antibiotic resistome were observed in autumn than in winter. The co-occurrence network identified multiple interactions between MGEs and various multidrug efflux pumps in winter, suggesting a potential for ARG dissemination. Multivariate correlation analyses and path modeling indicated that environmental factors driving microbial community changes predominantly influenced antibiotic resistome assembly in autumn, while the relative importance of MGEs increased significantly in winter. These findings suggest an elevated health risk associated with antimicrobial resistance in the Beibu Gulf during winter, attributed to the dissemination of ARGs by horizontal gene transfer. The observed seasonal variations highlight the dynamic nature of antibiotic resistance dissemination in coastal ecosystems, emphasizing the need for comprehensive surveillance and management measures to address the growing threat of antimicrobial resistance in vulnerable environments.

Copy number variations in autistic children.

Autism spectrum disorder (ASD) manifests as a neurodevelopmental condition marked by challenges in social communication, interaction and the performing of repetitive behaviors. The prevalence of autism increases markedly on an annual basis; however, the etiology remains incompletely understood. Cytogenetically visible chromosomal abnormalities, including copy number variations (CNVs), have been shown to contribute to the pathogenesis of ASD. More than 1% of ASD conditions can be explained based on a known genetic locus, whereas CNVs account for 5-10% of cases. However, there are no studies on the Saudi Arabian population for the detection of CNVs linked to ASD, to the best of our knowledge. Therefore, the aim of the present study was to explore the prevalence of CNVs in autistic Saudi Arabian children. Genomic DNA was extracted from the peripheral blood of 14 autistic children along with four healthy control children and then array-based comparative genomic hybridization (aCGH) was used to detect CNVs. Bioinformatics analysis of the aCGH results showed the presence of recurrent and non-recurrent deletion/duplication CNVs in several regions of the genome of autistic children. The most frequent CNVs were 1q21.2, 3p26.3, 4q13.2, 6p25.3, 6q24.2, 7p21.1, 7q34, 7q11.1, 8p23.2, 13q32.3, 14q11.1-q11.2 and 15q11.1-q11.2. In the present study, CNVs in autistic Saudi Arabian children were identified to improve the understanding of the etiology of autism and facilitate its diagnosis. Additionally, the present study identified certain possible pathogenic genes in the CNV region associated with several developmental and neurogenetic diseases.

Sciatic Nerve and Its Anatomical Variations: In-Depth Understanding Acquired During Dissection Classes.

Knowledge of anatomical variability is extremely important in order to better understand the etiology of pain, if present, or to avoid iatrogenic consequences. Sometimes the anatomical "anomalies" have the same anamnesis but different causes. For example, sciatic neuralgia may be caused by a herniated disc or it may have a different origin. The sciatic nerve (SN), also known as the ischial nerve, is the widest in the human body. This huge peripheral nerve originates from the roots of the lumbosacral plexus (L4-S3) and passes through the great sciatic foramen, under the piriformis muscle (PM). However, there is much variability in the pattern of SNs about the muscle, which has been known since the first half of the 20th century. In the present study, we describe six different case reports of anatomical variations of the SN and its interplay with the PM. The observations were made during dissection classes at the ICLO Teaching and Research Centre (Verona, Italy), on both male and female cadavers aged between 58 and 84 years. The SN was reported as a single and divided nerve into the tibial nerve (TN) and the common peroneal nerve (CPN), passing alone above, below, or between the PM. However, the two parts of the SN may also interact with the PM in different ways, adding to the anatomical variability. A thorough knowledge of the anatomical variations in any part of the human body is extremely important. The various techniques used, from imaging to autopsy or surgery, are also useful in the SN pathway. Thus, the anatomical features and the understanding of each variation are useful for a correct approach that can lead to an effective and correct treatment with a favorable outcome.