Diagnostic Accuracy of Various Radiological Measurements in the Evaluation and Differentiation of Flatfoot: A Cross-Sectional Study.

Arch angle is used to indicate flatfoot, but in some cases, it is not easily defined. The presence of flatfoot deformity remains difficult to diagnose due to a lack of reliable radiographic assessment tools. Although various assessment methods for flatfoot have been proposed, there is insufficient evidence to prove the diagnostic accuracy of the various tools. The main purpose of the study was to determine the best radiographic measures for flatfoot concerning the arch angle. Fifty-two feet radiographs from thirty-two healthy young females were obtained. Five angles and one index were measured using weight-bearing lateral radiographs; including arch angle, calcaneal pitch (CP), talar-first metatarsal angle (TFM), lateral talar angle (LTA), talar inclination angle (TIA) and navicular index (NI). Receiver-operating characteristics were generated to evaluate the flatfoot diagnostic accuracy for all radiographic indicators and Matthews correlation coefficient was calculated to determine the cutoff value for each measure. The strongest correlation was between arch angle and CP angle [r = -0.91, p ≤ 0.0001, 95% confidence interval (CI) (from -0.94 to -0.84)]. Also, significant correlations were found between arch angle and NI [r = 0.62, p ≤ 0.0001, 95% CI (0.42 to 0.76)], and TFM [r = 0.50, p ≤ 0.0001, 95% CI (from 0.266 to 0.68)]. Furthermore, CP (cutoff, 12.40) had the highest accuracy level with value of 100% sensitivity and specificity followed by NI, having 82% sensitivity and 89% specificity for the cutoff value of 9.90. In conclusion, CP angle is inversely correlated with arch angle and considered a significant indicator of flatfoot. Also, the NI is easy to define radiographically and could be used to differentiate flat from normal arched foot among young adults.

Epithelial PD-L1 expression at tumor front predicts overall survival in a cohort of oral squamous cell carcinomas from Sudan.

BACKGROUND: We recently described the tumor immune microenvironment (TIME) in oral squamous cell carcinomas (OSCC) from Sudan by assessing the core of the lesions. However, the invasive tumor front (ITF) is the most active part of OSCC lesions; thus, TIME should also be characterized at the ITF in this patient cohort. OBJECTIVES: We aimed to evaluate patterns of immune cell infiltration at the ITF in a cohort of OSCC patients from Sudan previously investigated at the tumor center and their association with clinicopathological parameters. METHODS: This study was performed on a prospective cohort of 22 OSCC patients attending Khartoum Dental Teaching Hospital with a median follow-up of 48 months. Inflammatory infiltrate densities of CD4-, CD8-, FoxP3-, CD20-, CD66b-, M1 (CD80/CD68)-, M2 (CD163/CD68)-, and PD-L1-positive cells were assessed at the ITF by immunohistochemistry, followed by digital quantitative analysis at the stromal and epithelial compartments separately. Histopathological parameters such as the worst pattern of invasion, differentiation, and tumor budding (TB) were also assessed. Correlations between clinicopathological parameters and survival analysis were investigated using SPSS. RESULTS: All inflammatory cell subsets investigated were found to be higher in the stromal compartment as compared to the epithelial one, except for the PD-L1+ subset. Stromal infiltration with the CD8+ cell subset was associated with low TB. Kaplan-Meier analyses identified higher epithelial and stromal CD4+ cell subsets. The presence of PD-L1 was found to be associated with unfavorable overall survival. Further, Cox's regression analysis using an age- and tumor-stage-adjusted model identified epithelial PD-L1 expression at the ITF as the only independent prognosticator. CONCLUSIONS: Epithelial PD-L1 expression at the ITF was found to be an independent prognostic biomarker for OSCC in a cohort of Sudanese patients.

Characterization of immune cell infiltrate in tumor stroma and epithelial compartments in oral squamous cell carcinomas of Sudanese patients.

BACKGROUND: Tumor immune infiltrate has been explored in oral squamous cell carcinoma (OSCC), but studies on simultaneous characterization of multiple immune cell subtypes separately in stromal and intraepithelial tumor compartments are limited. OBJECTIVES: We aimed to investigate the immune cell infiltrate in OSCC by using immunohistochemistry (IHC) for a panel of inflammatory cells in stromal and epithelial tumor compartments for a better characterization of the tumors. METHODS: Thirty-six OSCC lesions and nine normal oral mucosa (NOM) samples from patients attending Khartoum Dental Teaching Hospital, Sudan were investigated for presence of tumor infiltrating lymphocytes, tumor-associated macrophages, tumor-associated neutrophils, and PD-L1 positive cells in the inflammatory infiltrate by single and double IHC. Digital quantitative analysis (Aperio Technologies Inc.) was performed separately for stromal and epithelial compartments. RESULTS: OSCC cases displayed a higher inflammatory infiltrate in the associated stroma, but not in the epithelial compartment when compared to NOM. The immunosuppressive type of inflammatory infiltrate, that is, T regulatory cells (FoxP3+ cells) was identified to be significantly higher in the epithelial compartment of tumors with advanced clinical state. An immunoscore developed by combining intraepithelial FoxP3+ and CD4+ cells was found significantly higher in lesions from elderly patients, localized at toombak dipping-related sites, poorly differentiated OSCCs, or with loco-regional lymph node spreading. CONCLUSIONS: Despite heavy immune cell infiltration in tumor-associated stroma, the majority of OSCCs in this cohort displayed a low intraepithelial immune infiltration. An immunoscore based on combined CD4 and FoxP3 intraepithelial expression may serve as an indicator of advanced tumor progression and should be further investigated for its use as potential prognostic biomarker in OSCC.

Analysis of Salivary Mycobiome in a Cohort of Oral Squamous Cell Carcinoma Patients From Sudan Identifies Higher Salivary Carriage of Malassezia as an Independent and Favorable Predictor of Overall Survival.

Background: Microbial dysbiosis and microbiome-induced inflammation have emerged as important factors in oral squamous cell carcinoma (OSCC) tumorigenesis during the last two decades. However, the "rare biosphere" of the oral microbiome, including fungi, has been sparsely investigated. This study aimed to characterize the salivary mycobiome in a prospective Sudanese cohort of OSCC patients and to explore patterns of diversities associated with overall survival (OS). Materials and Methods: Unstimulated saliva samples (n = 72) were collected from patients diagnosed with OSCC (n = 59) and from non-OSCC control volunteers (n = 13). DNA was extracted using a combined enzymatic-mechanical extraction protocol. The salivary mycobiome was assessed using a next-generation sequencing (NGS)-based methodology by amplifying the ITS2 region. The impact of the abundance of different fungal genera on the survival of OSCC patients was analyzed using Kaplan-Meier and Cox regression survival analyses (SPPS). Results: Sixteen genera were identified exclusively in the saliva of OSCC patients. Candida, Malassezia, Saccharomyces, Aspergillus, and Cyberlindnera were the most relatively abundant fungal genera in both groups and showed higher abundance in OSCC patients. Kaplan-Meier survival analysis showed higher salivary carriage of the Candida genus significantly associated with poor OS of OSCC patients (Breslow test: p = 0.043). In contrast, the higher salivary carriage of Malassezia showed a significant association with favorable OS in OSCC patients (Breslow test: p = 0.039). The Cox proportional hazards multiple regression model was applied to adjust the salivary carriage of both Candida and Malassezia according to age (p = 0.029) and identified the genus Malassezia as an independent predictor of OS (hazard ratio = 0.383, 95% CI = 0.16-0.93, p = 0.03). Conclusion: The fungal compositional patterns in saliva from OSCC patients were different from those of individuals without OSCC. The fungal genus Malassezia was identified as a putative prognostic biomarker and therapeutic target for OSCC.

The Net Clinical Benefit of Rivaroxaban Compared to Low-Molecular-Weight Heparin in the Treatment of Cancer-Associated Thrombosis: Systematic Review and Meta-Analysis.

Cancer-associated thrombosis (CAT) carries significant morbidity and mortality. Low-molecular-weight heparin (LMWH) remains the standard of care, with recent systematic studies suggesting the efficacy and safety of rivaroxaban in the treatment of CAT. Uncertainty, however, remains regarding rivaroxaban efficacy and safety in real-world settings. We performed a systematic review and meta-analysis of studies comparing rivaroxaban to LMWH. We searched PubMed, MEDLINE, and EMBASE. The primary outcome was the net clinical benefit (NCB), while rates of major bleeding (MB), venous thromboembolism (VTE), clinically relevant nonmajor bleeding (CRNMB), and all-cause mortality events were secondary outcomes. Seventeen studies were included in the final analysis. Rivaroxaban had a better NCB (relative risk [RR] = 0.82; 95% CI = 0.75-0.89, Q = 10.51, I 2 = 0%), less VTE events (RR = 0.73, 95% CI = 0.65-0.82, Q = 6.76, I 2 = 0%), and lower all-cause mortality (RR = 0.72, 95% CI = 0.57-0.91, Q = 32.8, I 2 = 79%) compared to LMWH. Additionally, comparable MB events (RR = 1.07, 95% CI = 0.85-1.33, Q = 16.9, I 2 = 11%). However, CRNMB events were higher in the rivaroxaban group (RR = 2.02, 95% CI = 1.46-2.80, Q = 9.9, I 2 = 19%). Additional analyses demonstrated consistency of results. Our review encompassing data from randomized and real-world data suggested rivaroxaban superiority compared to LMWH in terms of a better NCB, fewer VTE events, lower all-cause mortality, and comparable MB risk while carrying a higher risk of CRNMB. These findings support the use of rivaroxaban in the treatment of CAT. Additionally, it warrants a sizable randomized controlled study testing the superiority of rivaroxaban versus LMWH formulation and ascertaining bleeding outcomes according to cancer type and site.

Morphological and Molecular Characterization of Orchid Fruit Development.

Efficient seed dispersal in flowering plants is enabled by the development of fruits, which can be either dehiscent or indehiscent. Dehiscent fruits open at maturity to shatter the seeds, while indehiscent fruits do not open and the seeds are dispersed in various ways. The diversity in fruit morphology and seed shattering mechanisms is enormous within the flowering plants. How these different fruit types develop and which molecular networks are driving fruit diversification is still largely unknown, despite progress in eudicot model species. The orchid family, known for its astonishing floral diversity, displays a huge variation in fruit dehiscence types, which have been poorly investigated. We undertook a combined approach to understand fruit morphology and dehiscence in different orchid species to get more insight into the molecular network that underlies orchid fruit development. We describe fruit development in detail for the epiphytic orchid species Erycina pusilla and compare it to two terrestrial orchid species: Cynorkis fastigiata and Epipactis helleborine. Our anatomical analysis provides further evidence for the split carpel model, which explains the presence of three fertile and three sterile valves in most orchid species. Interesting differences were observed in the lignification patterns of the dehiscence zones. While C. fastigiata and E. helleborine develop a lignified layer at the valve boundaries, E. pusilla fruits did not lignify at these boundaries, but formed a cuticle-like layer instead. We characterized orthologs of fruit-associated MADS-domain transcription factors and of the Arabidopsis dehiscence-related genes INDEHISCENT (IND)/HECATE 3 (HEC3), REPLUMLESS (RPL) and SPATULA (SPT)/ALCATRAZ (ALC) in E. pusilla, and found that the key players of the eudicot fruit regulatory network appear well-conserved in monocots. Protein-protein interaction studies revealed that MADS-domain complexes comprised of FRUITFULL (FUL), SEPALLATA (SEP) and AGAMOUS (AG) /SHATTERPROOF (SHP) orthologs can also be formed in E. pusilla, and that the expression of HEC3, RPL, and SPT can be associated with dehiscence zone development similar to Arabidopsis. Our expression analysis also indicates differences, however, which may underlie fruit divergence.

Terpenoid-rich Elettaria cardamomum extract prevents Alzheimer-like alterations induced in diabetic rats via inhibition of GSK3ß activity, oxidative stress and pro-inflammatory cytokines.

PURPOSE: Recent studies suggested that the non-familiar form of Alzheimer's disease (AD) could be consequence of metabolic syndrome and neuroinflammation. Elettaria cardamomum extract (EC) has exhibited antidiabetic, antioxidant and anti-inflammatory properties. This research was conducted to evaluate the effects of EC on AD-like alterations in rats induced by high fructose and high fat diet coupled with a single small dose of STZ (25 mg/kg) (T2DM rats). METHODS: Phytochemical analysis was carried out. Behavioral tests, immunohistochemical examination, biochemical analysis and gene expression determination were performed in treated and controls rats. RESULTS: The majority of EC compounds were terpenoids. EC extract administration for 8 weeks attenuated AD-like alterations. It reversed a T2DM-induced decline in cognitive functions in passive avoidance task and Morris water maze test. It significantly lowered the elevated hippocampal level of AChE activity and caspase-3 activity, an indicator of degeneration in T2DM rats Also, it reduced the accumulation of Aß and p-tau in the brain of T2DM rats. Furthermore, it elevated the suppressed glutamate receptor expression (AMPA GluR1 subunit and NMDA receptor subunits NR1, NR2A, NR2B). EC treatment reduced hippocampal lipid peroxidation marker malondialdehyde (MDA) and augmented antioxidant defensive system, including superoxide dismutase (SOD) and reduced glutathione (GSH). Meanwhile, it lowered hippocampal TNFα, IL ß1but not IL6 and reduced GSK-3ß in brainT2D rats. CONCLUSION: EC treatment could ameliorate AD-like alterations in T2DM rats through activation of blunted insulin signal transduction in the brain, attenuation of associated oxidative stress and neuroinflammation.

The low-affinity nerve growth factor receptor p75NTR identifies a transient stem cell-like state in oral squamous cell carcinoma cells.

BACKGROUND: Although several markers have been used for enrichment of cells with stem cell-like properties in oral squamous cell carcinoma (OSCC), isolation of a pure subpopulation is still a challenging task. Normal oral and esophageal keratinocyte stem cells have been previously isolated using the low-affinity nerve growth factor receptor p75NTR. OBJECTIVE: To investigate the potential of p75NTR as a marker for identification and isolation of oral cancer cells with stem cell-like properties. METHODS: Subpopulations of cells with high or low expression of p75NTR were sorted from OSCC-derived cells and compared for sphere/colony formation, in vivo tumor formation ability, expression of stem cell-related molecules, cell cycle distribution and drug resistance. RESULTS: p75NTR(High) cells exhibited statistically significant higher stem cell properties than p75NTR(Low) cells in all assays performed. Nevertheless, p75NTR(Low) subpopulation did also exhibit some stem cell features, but to a lesser extent. Propagation of p75NTR(Low) cells for several passages in culture showed that the expression of p75NTR could rise spontaneously. This finding was also supported by the similar expression of p75NTR by the xenografts generated by both subpopulations in NOD\SCID IL2Rg(null) mice. CONCLUSION: p75NTR can be used for isolating a subpopulation enriched for cells with stem cell-like properties in OSCC. De novo generation of p75NTR(High) cells from p75NTR(Low) cells suggests either that there is another subpopulation with stem cell features within the p75NTR(Low) cells, or that the p75NTR(Low) cells can dedifferentiate due to a contextually regulated equilibrium between stem cell-like cells and transit-amplifying neoplastic progenitors.