Anatomical Diversity in Femur bones: Understanding the Morphological Variability for Surgical and Prosthetic Applications / Diversidad Anatómica en Huesos Fémur: Comprensión de la Variabilidad Morfológica para Aplicaciones Quirúrgicas y Protésicas

SUMMARY: The femur, the body's longest bone, plays a critical role in orthopaedics and radiology. Understanding its anatomy, particularly the neck-shaft angle (NSA), is vital for diagnosing bone issues and designing hip implants. While some Asian populations' femur measurements have been studied, there is a research gap concerning Sri Lankans. This study aimed to fill this gap by examining the proximal femur's anatomy in the Sri Lankan population. We analysed 45 adult human femurs (26 right, 19 left) of unknown sex, ethically sourced from the University of Sri Jayewardenepura. Femurs with fractures or pathologies were excluded. Precise measurements were recorded using digital vernier callipers, with millimetre accuracy. Parameters included mean femoral length, vertical and transverse femoral head diameters, neck axis and neck length. Each measurement was taken three times to minimize subjectivity. Right femurs had a mean length of 42.8 mm (SD±2.64), while left femurs measured 43.53 mm (SD±3.27). Mean NSA was 125.78º (SD±4.45) for left femurs and 127.59º (SD±2.06) for right. Mean femoral head diameters were 4.09mm (SD±0.30) (right) and 4.12mm (SD±0.31) (left). Mean anterior neck lengths of the right and left were 2.61 (SD±0.54) and 2.71(SD±0.50) respectively. Comparing our findings with other Asian populations highlighted significant variations in femur measurements. These discrepancies emphasize the need for population-specific data for orthopaedic interventions and raise questions about the suitability of imported prosthetics. Differences in femur length, neck length, and NSA between sides suggest potential challenges in using implants designed for one side on the other. This study underscores the necessity of population-specific data in orthopaedics, as femur measurements differ even among Asian populations. Further research and statistical analysis are essential for tailoring orthopaedic solutions to individual populations. The findings also suggest a potential need for locally manufactured prosthetics to better suit the Sri Lankan population.

El fémur, el hueso más largo del cuerpo, desempeña un papel fundamental en ortopedia y radiología. Comprender su anatomía, en particular el ángulo cuello-diáfisis (NSA), es vital para diagnosticar problemas óseos y diseñar implantes de cadera. Si bien se han estudiado las medidas del fémur de algunas poblaciones asiáticas, existe un vacío en la investigación sobre los habitantes de Sri Lanka. Este estudio tuvo como objetivo examinar la anatomía del fémur proximal en la población de Sri Lanka. Analizamos 45 fémures humanos adultos (26 derechos, 19 izquierdos) de sexo desconocido, obtenidos éticamente de la Universidad de Sri Jayewardenepura. Se excluyeron fémures con fracturas o patologías. Se registraron mediciones precisas utilizando calibradores vernier digitales, con precisión milimétrica. Los parámetros incluyeron la longitud femoral media, los diámetros vertical y transversal de la cabeza femoral, el eje del cuello y la longitud del cuello. Cada medición se tomó tres veces para minimizar la subjetividad. Los fémures derechos tuvieron una longitud media de 42,8 mm (DE ± 2,64), mientras que los fémures izquierdos midieron 43,53 mm (DE ± 3,27). La NSA media fue de 125,78º (DE±4,45) para el fémur izquierdo y de 127,59º (DE±2,06) para el derecho. Los diámetros medios de la cabeza femoral fueron 4,09 mm (DE ± 0,30) (derecha) y 4,12 mm (DE ± 0,31) (izquierda). Las longitudes medias del cuello anterior de la derecha y la izquierda fueron 2,61 (DE ± 0,54) y 2,71 (DE ± 0,50) respectivamente. La comparación de nuestros hallazgos con otras poblaciones asiáticas destacó variaciones significativas en las medidas del fémur. Estas discrepancias enfatizan la necesidad de datos específicos de la población para las intervenciones ortopédicas y plantean dudas sobre la idoneidad de las prótesis importadas. Las diferencias en la longitud del fémur, la longitud del cuello y la NSA entre lados sugieren posibles desafíos al utilizar implantes diseñados para un lado en el otro. Este estudio subraya la necesidad de datos específicos de la población en ortopedia, ya que las mediciones del fémur difieren incluso entre las poblaciones asiáticas. Es esencial realizar más investigaciones y análisis estadísticos para adaptar las soluciones ortopédicas a poblaciones individuales. Los hallazgos también sugieren una posible necesidad de prótesis fabricadas localmente para adaptarse mejor a la población de Sri Lanka.

Salivary Interleukin Levels in Oral Squamous Cell Carcinoma and Oral Epithelial Dysplasia: Findings from a Sri Lankan Study.

The incidence of oral squamous cell carcinoma (OSCC), and its precursor, oral epithelial dysplasia (OED), is on the rise, especially in South Asia. OSCC is the leading cancer in males in Sri Lanka, with >80% diagnosed at advanced clinical stages. Early detection is paramount to improve patient outcome, and saliva testing is a promising non-invasive tool. The aim of this study was to assess salivary interleukins (lL1ß, IL6, and IL8) in OSCC, OED and disease-free controls in a Sri Lankan study cohort. A case-control study with OSCC (n = 37), OED (n = 30) patients and disease-free controls (n = 30) was conducted. Salivary lL1ß, IL6, and IL8 were quantified using enzyme-linked immuno-sorbent assay. Comparisons between different diagnostic groups and potential correlations to risk factors were assessed. Salivary levels for the three tested interleukins increased from disease-free controls through OED, and were highest in OSCC samples. Furthermore, the levels of IL1ß, IL6, and IL8 increased progressively with OED grade. The discrimination between patients (OSCC and OED) and controls, as assessed by AUC of receiver operating characteristic curves, was 0.9 for IL8 (p = 0.0001) and 0.8 for IL6 (p = 0.0001), while IL1ß differentiated OSCC from controls (AUC 0.7, p = 0.006). No significant associations were found between salivary interleukin levels and smoking, alcohol, and betel quid risk factors. Our findings suggest that salivary IL1ß, IL6, and IL8 are associated with disease severity of OED, and are potential biomarkers for predicting disease progression in OED, and the screening of OSCC.

The Risk of Oral Cancer among Different Categories of Exposure to Tobacco Smoking in Sri Lanka

Background: The global incidence of oral squamous cell carcinoma (OSCC) is on the rise with no improvement seen in survival rates. Tobacco consumption varies depending on geographic location, ethnicity and culture. The present case-controlled study aimed to determine the relative risk of OSCC for different tobacco consumption patterns in a selected Sri Lankan population. Methods: One hundred and five patients with histopathologically confirmed OSCC attending the National Cancer Institute (Apeksha Hospital) of Sri Lanka and 210 age and gender-matched controls from the community responded to an interviewer-administered questionnaire regarding their smoking and betel-quid chewing (with/ without smokeless tobacco) habits were included in the study. The odds ratios (OR) and 95% confidence intervals (CI) were calculated. p<0.05 was considered as statistically significant. Results: The overall risk of OSCC increased 2.93-fold for smokers. Those smoking two packets of cigarettes or more per day (OR=5.56; 95% CI-2.822- 10.984; p=0.000) had more than double the risk of OSCC than those smoking 1-2 packets per day. Smoking for more than 20 years had a 3.4-fold risk of OSCC. Consumption of betel quid containing tobacco (smokeless tobacco) had a 4.26-fold higher risk for OSCC (OR=4.26; 95% CI-2.21-8.21; p=0.000), and the risk increased when all four ingredients (betel leaf, slaked lime, areca nut, and tobacco) were consumed together (OR=4.26; 95% CI-2.34-7.74; p=0.000). The combined effect from concurrent smoking and betel chewing emerged as the highest risk for OSCC (OR=15.34) which significantly exceeded the risks evident for the two habits practised in isolation from each other. Conclusions: Use of smokeless tobacco, consumption of all four ingredients together, duration of smoking, the number of cigarettes smoked per day and combined consumption of betel quid and smoking are significant risk factors in the development of OSCC among Sri Lankans.

Distinct microbiome profiles and biofilms in Leishmania donovani-driven cutaneous leishmaniasis wounds.

The endemic strain of Leishmania donovani in Sri Lanka causes cutaneous leishmaniasis (CL) rather than more common visceral form. We have visualized biofilms and profiled the microbiome of lesions and unaffected skin in thirty-nine CL patients. Twenty-four lesions (61.5%) were biofilm-positive according to fluorescence in situ hybridization. Biopsies of biofilm-positive lesions were dominated by Pseudomonas, class Bacilli and Enterobacteriaceae and distinguished by significantly lower community evenness. Higher relative abundance of a class Bacilli OTU was detected in wound swabs versus contralateral skin. Wound swabs and biopsies had significantly distinct microbiome profiles and lower diversity compared to unaffected skin. Greater abundances of potentially pathogenic organisms were observed in wet ulcers, lesions with high parasite loads and large wounds. In summary, more than half of L. donovani associated CL wounds harboured biofilms and the wounds exhibited a distinct, less diverse, microbiome than unaffected skin.

Diagnostic salivary biomarkers in oral cancer and oral potentially malignant disorders and their relationships to risk factors - A systematic review.

INTRODUCTION: Oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) are a significant health burden globally. Smoking, alcohol, and betel quid are the main risk factors. Lack of screening methods has been highlighted as a significant challenge in management. Salivary biomarkers are proposed as noninvasive diagnostic tools. The aim of this systematic review was to study salivary biomarkers reported in OSCC and OPMD. Specific objectives were to select a salivary biomarker panel suitable for early detection of OSCC and OPMD and to assess relationships between salivary biomarkers and risk factors. METHODS: Electronic literature search was conducted in academic databases (Scopus, Medline, Embase and Web of Science) without any restrictions. Following calibration, two blinded reviewers screened the studies and extracted data. A risk of bias assessment was conducted using Newcastle Ottawa scale. 295 studies were included with descriptive data analysis. EXPERT OPINION: A salivary biomarker panel including Interleukin (IL) 1ß, IL6, and IL8 was selected for OSCC and OPMD. Reported relationships between salivary biomarkers and risk factors are discussed and research gaps are highlighted. Future research should be directed to assess potential salivary biomarkers and their relationships to risk factors in order to understand the biomarker's role in disease initiation.

Diagnosing human cutaneous leishmaniasis using fluorescence in situ hybridization.

Cutaneous leishmaniasis (CL) is endemic in Sri Lanka. Giemsa-stained slit-skin-smears (SSS-Giemsa) and histology are routinely used in diagnosis with a sensitivity of 40-70%. PCR currently has limited accessibility. Therefore, we assessed the sensitivity and specificity of a previously described fluorescence in situ hybridization assay, on skin smears and biopsy samples to overcome the limitations encountered with routine diagnostic methods.Samples from a total of 123 suspected CL patients were collected and subjected to SSS-Giemsa, fluorescence in situ hybridization (FISH) on slit skin smears (SSS-FISH), formalin-fixed-paraffin-embedded-tissues stained with Hematoxylin & Eosin staining (FFPE-H&E) and FISH on formalin-fixed-paraffin-embedded-tissues (FFPE-FISH). Negative controls of 61 patient samples were collected from a CL non-endemic area and subjected to the same procedures. The gold standard PCR was used as a comparator. For FISH, two previously described cyanine 3 tagged Leihsmania genus-specific probes were used.Compared to PCR, SSS-Giemsa, SSS-FISH, FFPE-H&E, and FFPE-FISH had sensitivities of 76.5%, 79.1%, 50.4% and 80.9%, respectively. Routine diagnostic tests (SSS-Giemsa and FFPE-H&E) had a specificity of 100%. SSS-FISH and FFPE-FISH had specificities of 96.7% and 93.4%, respectively. FFPE-FISH had a statistically significant higher diagnostic performance than FFPE-H&E (p < 0.001). The relative performance of SSS-Giemsa, SSS-FISH and FFPE-FISH was similar (p > 0.05 for all comparisons).We conclude that FFPE-FISH is a more accurate diagnostic tool than FFPE-H&E. SSS-FISH did not have an additional advantage over SSS-Giemsa in diagnosis. However, SSS-FISH could be recommended as a minimally invasive method in studies assessing wound healing where immunological probes are used.

Transcriptomic abnormalities in peripheral blood in bipolar disorder, and discrimination of the major psychoses.

We performed a transcriptome-wide meta-analysis and gene co-expression network analysis to identify genes and gene networks dysregulated in the peripheral blood of bipolar disorder (BD) cases relative to unaffected comparison subjects, and determined the specificity of the transcriptomic signatures of BD and schizophrenia (SZ). Nineteen genes and 4 gene modules were significantly differentially expressed in BD cases. Thirteen gene modules were shown to be differentially expressed in a combined case-group of BD and SZ subjects called "major psychosis", including genes biologically linked to apoptosis, reactive oxygen, chromatin remodeling, and immune signaling. No modules were differentially expressed between BD and SZ cases. Machine-learning classifiers trained to separate diagnostic classes based solely on gene expression profiles could distinguish BD cases from unaffected comparison subjects with an area under the curve (AUC) of 0.724, as well as BD cases from SZ cases with AUC = 0.677 in withheld test samples. We introduced a novel and straightforward method called "polytranscript risk scoring" that could distinguish BD cases from unaffected subjects (AUC = 0.672) and SZ cases (AUC = 0.607) significantly better than expected by chance. Taken together, our results highlighted gene expression alterations common to BD and SZ that involve biological processes of inflammation, oxidative stress, apoptosis, and chromatin regulation, and highlight disorder-specific changes in gene expression that discriminate the major psychoses.

Diagnosing Cutaneous leishmaniasis using Fluorescence in Situ Hybridization: the Sri Lankan Perspective.

Cutaneous leishmaniasis (CL) caused by Leishmania donovani MON-37 is becoming a major public health problem in Sri Lanka, with 100 new cases per month being reported in endemic regions. Diagnosis of CL is challenging for several reasons. Due to relative specificity and rapidity we propose Fluorescence in Situ Hybridization as a diagnostic tool for CL. The objective was to evaluate the potential of Fluorescence in Situ Hybridization as a diagnostic method for Cutaneous leishmaniasis in Sri Lanka. Literature on current laboratory tests used to diagnose Cutaneous leishmaniasis in Sri Lanka and globally was reviewed. Sri Lankan data were reviewed systematically following the PRISMA guidelines. A narrative of the results is presented. There is currently no gold standard diagnostic method for Cutaneous leishmaniasis. Fluorescence in Situ Hybridization has been previously applied to detect dermal pathologies including those involving infectious agents, and its use to detect the Leishmania parasite in human cutaneous lesions reported in small number of studies, generally with limited numbers of subjects. Advantages of FISH has been specificity, cost and ease-of-use compared to the alternatives. Based on the available literature and our current work, FISH has potential for diagnosing CL and should now be evaluated in larger cohorts in endemic regions. FISH for CL diagnosis could find application in countries such as Sri Lanka, where laboratory facilities may be limited in rural areas where the disease burden is highest.

Transcriptome-wide mega-analyses reveal joint dysregulation of immunologic genes and transcription regulators in brain and blood in schizophrenia.

The application of microarray technology in schizophrenia research was heralded as paradigm-shifting, as it allowed for high-throughput assessment of cell and tissue function. This technology was widely adopted, initially in studies of postmortem brain tissue, and later in studies of peripheral blood. The collective body of schizophrenia microarray literature contains apparent inconsistencies between studies, with failures to replicate top hits, in part due to small sample sizes, cohort-specific effects, differences in array types, and other confounders. In an attempt to summarize existing studies of schizophrenia cases and non-related comparison subjects, we performed two mega-analyses of a combined set of microarray data from postmortem prefrontal cortices (n=315) and from ex-vivo blood tissues (n=578). We adjusted regression models per gene to remove non-significant covariates, providing best-estimates of transcripts dysregulated in schizophrenia. We also examined dysregulation of functionally related gene sets and gene co-expression modules, and assessed enrichment of cell types and genetic risk factors. The identities of the most significantly dysregulated genes were largely distinct for each tissue, but the findings indicated common emergent biological functions (e.g. immunity) and regulatory factors (e.g., predicted targets of transcription factors and miRNA species across tissues). Our network-based analyses converged upon similar patterns of heightened innate immune gene expression in both brain and blood in schizophrenia. We also constructed generalizable machine-learning classifiers using the blood-based microarray data. Our study provides an informative atlas for future pathophysiologic and biomarker studies of schizophrenia.

Gene expression profiling in treatment-naive schizophrenia patients identifies abnormalities in biological pathways involving AKT1 that are corrected by antipsychotic medication.

Distinct gene expression profiles can be detected in peripheral blood mononuclear cells (PBMCs) in patients with schizophrenia; however, little is known about the effects of antipsychotic medication. This study compared gene expression profiles in PMBCs from treatment-naive patients with schizophrenia before and after antipsychotic drug treatment. PBMCs were obtained from 10 treatment-naive schizophrenia patients before and 6 wk after initiating antipsychotic drug treatment and compared to PMBCs collected from 11 healthy community volunteers. Genome-wide expression profiling was conducted using Illumina HumanHT-12 expression bead arrays and analysed using significance analysis of microarrays. This analysis identified 624 genes with altered expression (208 up-regulated, 416 down-regulated) prior to antipsychotic treatment (p < 0.05) including schizophrenia-associated genes AKT1, DISC1 and DGCR6. After 6-8 wk treatment of patients with risperidone or risperidone in combination with haloperidol, only 106 genes were altered, suggesting that the treatment corrected the expression of a large proportion of genes back to control levels. However, 67 genes continued to show the same directional change in expression after treatment. Ingenuity® pathway analysis and gene set enrichment analysis implicated dysregulation of biological functions and pathways related to inflammation and immunity in patients with schizophrenia. A number of the top canonical pathways dysregulated in treatment-naive patients signal through AKT1 that was up-regulated. After treatment, AKT1 returned to control levels and less dysregulation of these canonical pathways was observed. This study supports immune dysfunction and pathways involving AKT1 in the aetiopathophysiology of schizophrenia and their response to antipsychotic medication.