KDM3A knockdown regulates COMP, LOX, COL8A1 and ACOT1 genes in myocardial fibrosis.

Cardiovascular disease (CVD) is one of the main causes of death in Saudi Arabia. Cardiac remodeling plays a critical role in the pathophysiology of heart failure. Major focus of our study was to identify crucial genes involved in the pathological remodeling of the heart caused by pressure overload. We utilized various in-silico tools to analyze and interpret microarray data obtained from the Gene Expression Omnibus (GEO) database (GSE120739), including GEO2R analysis, Metascape analysis, WebGestalt analysis, and IPA (Ingenuity pathway analysis). Our findings indicate that certain genes, including Cartilage Oligomeric Matrix Protein (COMP), collagen type VIII alpha 1 chain (COL8A1) and Lysyl Oxidase (LOX) under the influence caused by knockdown of KDM3A, were down regulated by the extracellular matrix pathway. Moreover, genes, such as Acyl-CoA Thioesterase 1 (ACOT1) were up regulated by the fatty acid metabolism pathway. Overexpression of lysine-specific demethylase 3A (KDM3A) leads to the up regulation of fibrosis-related genes COMP, COL8A1, and LOX and the down regulation of ACOT1, result in enhanced fibrosis and heart failure. Our results suggest that COMP, COL8A1, LOX, and ACOT1 warrant further investigation in the development of cardiac fibrosis and as potential biomarkers for causing heart failure.

Clinical versus fixed warfarin dosing and the impact on quality of anticoagulation (The ClinFix trial).

Different dosing strategies exist to initiate warfarin, most commonly fixed warfarin dosing (FWD), clinical warfarin dosing (CWD), and genetic-guided warfarin dosing (GWD). Landmark trials have shown GWD to be superior when compared to FWD in the EU-PACT trial or CWD in the GIFT trial. COAG trial did not show differences between GWD and CWD. We aim to compare the anticoagulation quality outcomes of CWD and FWD. This is a prospective cohort study with a retrospective comparator. Recruited subjects in the CWD (prospective) arm were initiated on warfarin according to the clinical dosing component of the algorithm published in www.warfarindosing.org. The primary efficacy outcome was the percentage time in the therapeutic range (PTTR) from day 3 to 6 till day 28 to 35. The study enrolled 122 and 123 patients in the CWD and FWD, respectively. The PTTR did not differ statistically between CWD and FWD (62.2 ± 26.2% vs. 58 ± 25.4%, p = 0.2). There was also no difference between both arms in the percentage of visits with extreme subtherapeutic international normalized ratio (INR) (<1.5; 15 ± 18.3% vs. 16.8 ± 19.1%, p = 0.44) or extreme supratherapeutic INR (>4; 7.7 ± 14.7% vs. 7.5 ± 12.4%, p = 0.92). We conclude that CWD did not improve the anticoagulation quality parameters compared to the FWD method.

Diabetic retinopathy screening through artificial intelligence algorithms: A systematic review.

Diabetic retinopathy (DR) poses a significant challenge in diabetes management, with its progression often asymptomatic until advanced stages. This underscores the urgent need for cost-effective and reliable screening methods. Consequently, the integration of artificial intelligence (AI) tools presents a promising avenue to address this need effectively. We provide an overview of the current state of the art results and techniques in DR screening using AI, while also identifying gaps in research for future exploration. By synthesizing existing database and pinpointing areas requiring further investigation, this paper seeks to guide the direction of future research in the field of automatic diabetic retinopathy screening. There has been a continuous rise in the number of articles detailing deep learning (DL) methods designed for the automatic screening of diabetic retinopathy especially by the year 2021. Researchers utilized various databases, with a primary focus on the IDRiD dataset. This dataset consists of color fundus images captured at an ophthalmological clinic situated in India. It comprises 516 images that depict various stages of DR and diabetic macular edema. Each of the chosen papers concentrates on various DR signs. Nevertheless, a significant portion primarily focused on detecting exudates, which remains insufficient to assess the overall presence of this disease. Various AI methods have been employed to identify DR signs. Among the chosen papers, 4.7 % utilized detection methods, 46.5 % employed classification techniques, 41.9 % relied on segmentation, and 7 % opted for a combination of classification and segmentation. Metrics calculated from 80 % of the articles employing preprocessing techniques demonstrated the significant benefits of this approach in enhancing results quality. In addition, multiple DL techniques, starting by classification, detection then segmentation. Researchers used mostly YOLO for detection, ViT for classification, and U-Net for segmentation. Another perspective on the evolving landscape of AI models for diabetic retinopathy screening lies in the increasing adoption of Convolutional Neural Networks for classification tasks and U-Net architectures for segmentation purposes; however, there is a growing realization within the research community that these techniques, while powerful individually, can be even more effective when integrated. This integration holds promise for not only diagnosing DR, but also accurately classifying its different stages, thereby enabling more tailored treatment strategies. Despite this potential, the development of AI models for DR screening is fraught with challenges. Chief among these is the difficulty in obtaining the high-quality, labeled data necessary for training models to perform effectively. This scarcity of data poses significant barriers to achieving robust performance and can hinder progress in developing accurate screening systems. Moreover, managing the complexity of these models, particularly deep neural networks, presents its own set of challenges. Additionally, interpreting the outputs of these models and ensuring their reliability in real-world clinical settings remain ongoing concerns. Furthermore, the iterative process of training and adapting these models to specific datasets can be time-consuming and resource-intensive. These challenges underscore the multifaceted nature of developing effective AI models for DR screening. Addressing these obstacles requires concerted efforts from researchers, clinicians, and technologists to develop new approaches and overcome existing limitations. By doing so, a full potential of AI may transform DR screening and improve patient outcomes.

Clinical impact of multidrug-resistant bacterial infections in patients with cirrhosis.

Aim: Recently, the emergency of multidrug-resistant organisms (MDRO) has complicated the management of bacterial infections (BI) in cirrhosis. We aimed to assess their clinical impact on patients with decompensated cirrhosis. Methods: A retrospective study included consecutive cirrhotic patients hospitalized for acute decompensation (AD) between January 2010 and December 2019. Results: A total of 518 AD admissions in 219 patients were included, with 260 BI episodes (50.2%). MDRO prevalence was 38.2% of the total isolates. Recent antibiotic use (OR = 4.91), nosocomial infection (OR = 2.95), and healthcare-associated infection (OR = 3.45) were their main risk factors. MDROs were associated with empiric treatment failure (OR = 23.42), a higher prevalence of sepsis (OR = 4.93), ACLF (OR = 3.42) and mortality. Conclusion: The clinical impact of MDROs was pejorative, with an increased risk of empiric treatment failure, organ failure and death.

In recent years, an increasing spread of multidrug-resistant bacteria had been observed worldwide. The emergence of these strains could represent a major problem in fragile patients such as cirrhotic patients. Over 10 years, our study analyzed the bacteriological profile of cirrhotic patient infections. The multidrug-resistant bacteria prevalence was 38.2%. Exposure to healthcare facilities and recent antibiotic use, were their main risk factors. These strains had a negative impact with an increased risk of treatment failure and death.

New Study Alert! Significant prevalence and negative clinical impact of multidrug-resistant organism (MDRO) infections in patients with cirrhosis. Main risk factors: recent antibiotic use and exposure to healthcare facilities. #cirrhosis #bacterialinfection #antibiotherapy #resistance.

MedKnee: A New Deep Learning-Based Software for Automated Prediction of Radiographic Knee Osteoarthritis.

In computer-aided medical diagnosis, deep learning techniques have shown that it is possible to offer performance similar to that of experienced medical specialists in the diagnosis of knee osteoarthritis. In this study, a new deep learning (DL) software, called "MedKnee" is developed to assist physicians in the diagnosis process of knee osteoarthritis according to the Kellgren and Lawrence (KL) score. To accomplish this task, 5000 knee X-ray images obtained from the Osteoarthritis Initiative public dataset (OAI) were divided into train, valid, and test datasets in a ratio of 7:1:2 with a balanced distribution across each KL grade. The pre-trained Xception model is used for transfer learning and then deployed in a Graphical User Interface (GUI) developed with Tkinter and Python. The suggested software was validated on an external public database, Medical Expert, and compared with a rheumatologist's diagnosis on a local database, with the involvement of a radiologist for arbitration. The MedKnee achieved an accuracy of 95.36% when tested on Medical Expert-I and 94.94% on Medical Expert-II. In the local dataset, the developed tool and the rheumatologist agreed on 23 images out of 30 images (74%). The MedKnee's satisfactory performance makes it an effective assistant for doctors in the assessment of knee osteoarthritis.

Design and synthesis of new quinazolinone derivatives: investigation of antimicrobial and biofilm inhibition effects.

New quinazolin-4-ones 9-32 were synthesized in an attempt to overcome the life-threatening antibiotic resistance phenomenon. The antimicrobial screening revealed that compounds 9, 15, 16, 18, 19, 20 and 29 are the most broad spectrum antimicrobial agents in this study with safe profile on human cell lines. Additionally, compounds 19 and 20 inhibited biofilm formation in Pseudomonas aeruginosa, which is regulated by quorum sensing system, at sub-minimum inhibitory concentrations (sub-MICs) with IC50 values 3.55 and 6.86 µM, respectively. By assessing other pseudomonal virulence factors suppression, it was found that compound 20 decreased cell surface hydrophobicity compromising bacterial cells adhesion, while both compounds 19 and 20 curtailed the exopolysaccharide production which constitutes the major component of the matrix binding biofilm components together. Also, at sub-MICs Pseudomonas cells twitching motility was impeded by compounds 19 and 20, a trait which augments the cells pathogenicity and invasion potential. Molecular docking study was performed to further evaluate the binding mode of candidates 19 and 20 as inhibitors of P. aeruginosa quorum sensing transcriptional regulator PqsR. The achieved results demonstrate that both compounds bear promising potential for discovering new anti-biofilm and quorum quenching agents against Pseudomonas aeruginosa without triggering resistance mechanisms as the normal bacterial life cycle is not disturbed.

Prevalence and Distribution of Macular Fluid with Central Retinal Artery Occlusion and Anterior Ischemic Optic Neuropathy.

Purpose: To examine the prevalence and distribution of fluid within a cohort of eyes with acute central retinal artery occlusion (CRAO) and non-arteritic anterior ischemic optic neuropathy (AION) using optical coherence tomography (OCT). Methods: A retrospective analysis of patient records and OCT imaging. Patients presenting with acute CRAO or AION who had available macular OCT imaging and no co-morbidities known to cause macular fluid were included in the analysis. Baseline characteristics, visual acuity (VA), and fluid presence and distribution among the retinal layers were recorded. Results: In the 16 eyes with acute CRAO, fluid was noted in 5 eyes (31%), which was mainly subretinal (3 eyes) or intraretinal located within the outer retinal layers (3 eyes). Only one eye had inner retinal cysts. Of the 11 eyes with acute AION, fluid was present in 8 eyes (73%). Subretinal fluid was noted in 4 eyes and extended to the foveal area in 3 of them, and outer retinal versus inner retinal cysts were noted in 6 versus 3 eyes, respectively. None of the eyes showed hard exudate deposition. In the small subset of eyes with CRAO and macular fluid that were followed-up, VA improved, while in eyes with AION, VA remained stable. Conclusion: Macular fluid on OCT is not an uncommon feature of acute CRAO and AION and is mainly distributed within the outer retinal layers or subretinal space. Fluid is an understudied feature of retinal and optic nerve head infarction and may have a role in predicting neuronal damage extent and visual outcome.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants Compared with Warfarin in Patients with Low Bodyweight who have Atrial Fibrillation: A Systematic Review and Meta-analysis.

INTRODUCTION: oral anticoagulant (DOAC) agents are becoming the anticoagulation strategy of choice for most clinical risks for which they are indicated. However, residual uncertainty remains regarding their use in preventing stroke in patients with low bodyweight [< 60 kg or body mass index (BMI) < 18 kg/m2]. We have carried out pooled systematic analyses of published studies to determine the efficacy and safety of these agents compared with warfarin in stroke prevention in patients with low bodyweight. METHODS: We carried out a comprehensive search of electronic databases from inception to June 2023 for eligible studies reporting on the efficacy and safety of direct oral anticoagulants versus warfarin in patients with atrial fibrillation who had low bodyweight. These include PubMed, EMBASE, the Cochrane Database of Systematic Reviews, the Science Citation Index, and the Database of Abstracts of Reviews of Effectiveness. Using the random effects model, derived pooled odd ratios (with their corresponding confidence intervals) of mortality outcomes in patient cohorts exposed to direct oral anticoagulants versus warfarin in patients with atrial fibrillation who had low bodyweight. RESULTS: Nine studies (n = 159,514 patients) were included in our meta-analysis. DOAC analogs were associated with lower stroke recurrence compared with warfarin [odds ratio (OR) 0.66, 95% confidence interval (CI) 0.49-0.9]; however, there was no significant difference in the composite outcome (OR 0.81, 95% CI 0.59-1.09) and mortality (OR 0.82, 95% CI 0.48-1.41). Additionally, DOAC analogs showed a significant reduction in major bleeding events by 30% compared with warfarin (OR 0.70, 95% CI 0.62-0.80). CONCLUSION: In this pooled meta-analytical synthesis of studies comprising both real-world and randomized controlled data, the use of DOAC analogs in patients with atrial fibrillation and low bodyweight (< 60 kg or BMI < 18 kg/m2) was associated with a significant reduction in risks of stroke and major bleeding compared with patient cohorts stabilized on warfarin-based therapy. There was uncertainty regarding the composite outcome and mortality point estimate between these two anticoagulation strategies. This finding helps to resolve the uncertainty associated with the use of DOACs in this cohort. Additionally, it suggests the need for confirmatory non-inferiority randomized controlled trials evaluating DOACs versus warfarin in this cohort of patients.

Application of a Revised Tissue Saving Protocol for Combined Topography-Guided Photorefractive Keratectomy and Cross-Linking in a Cohort Having Pellucid Marginal Degeneration.

Purpose: To evaluate the efficiency, safety, and stability of a revised tissue-saving treatment protocol in a cohort having pellucid marginal degeneration (PMD). Methods: A retrospective cohort study was conducted on patients with PMD and no previous treatments. A revised protocol of topo-guided photorefractive keratectomy to be followed by customized phototherapeutic keratectomy and then corneal crosslinking was evaluated by comparing the pre and postoperative outcomes regarding visual (subjective refraction) and topographic (using data from Sirius CSO topography software) outcomes. Results: There were both statistically significant and clinically relevant improvements in the postoperative parameters, where each of the unaided and corrected visual acuity, spherical equivalent, refractive cylinder, K readings, topographic cylinder, inferior minus superior difference at the 2- and 4- mm diameters, coma aberration, and higher order aberrations were significantly better postoperatively (all p values were less than 0.01, except for maximum k readings where the p-value was 0.017). The safety and efficacy indices for the surgical procedure were remarkably high (1.53 ± 0.70 and 0.90 ± 0.32, respectively). Conclusion: Our proposed tissue-saving protocol (which showed satisfactory results in keratoconus cases according to a previously published article by our research team) has proven its successful outcomes (both topographically and visually) in cases of PMD, which is a rare ectatic entity with guarded prognosis using the available conventional ectasia treatment modalities.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants in Low Body Weight Patients with Atrial Fibrillation: A Systematic Review and Meta-analysis.

INTRODUCTION: Direct oral anticoagulant (DOAC) agents are established as the anticoagulation strategy of choice for a variety of clinical risks. Despite this, uncertainty still exists with regard to their efficacy and safety for the prevention of stroke and systemic embolism in some patient populations; most notably those with low body weight (LBW) (<60 kg or body mass index [BMI] <18 kg/m2). Currently, there is a paucity of trial and non-trial data to support a prescriptive recommendation for their use in these patient cohorts. We have carried out a pooled systematic review of the most up to date published data of patients stabilized on various DOAC analogs with the view to ascertaining the exact matrices of their efficacy and safety in these cohorts of patients. METHODS: We initially carried out a comprehensive search of databases from inception to June 2023 for eligible studies exploring the efficacy and safety of various analogs of direct oral anticoagulants in patients with atrial fibrillation who had low body weight. Databases accessed include PubMed, EMBASE, the Science Citation Index, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effectiveness. We carried out a weighted comparison of derived pooled odd ratios (with their corresponding confidence intervals) of mortality outcomes between various DOACs using the random effects model. RESULTS: Thirteen studies (n = 165,205 patients) were included in our meta-analysis. DOAC analogs were associated with increased stroke-related events, composite outcome, and mortality in low body weight patients compared to non-low body weight patients (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.17-1.92), (OR 1.55, 95% CI 1.29-1.86), (OR 2.92, 95% CI 1.87-4.58), respectively. There was no significant difference in the safety outcome (major bleeding events) between the DOAC analogs (OR 1.19, 95% CI 0.93-1.52). DISCUSSION: In this meta-analytical review comprising both real-world and randomized controlled studies, the use of DOAC analogs in low body weight patients (body weight of <60 kg or BMI<18 kg/m2) with atrial fibrillation was associated with increased risks of stroke-related events, composite outcomes, and mortality compared to non-low body weight cohorts patients. At the same time, there was no significant difference in terms of major bleeding events. This finding has provided the first resolution of pervading uncertainty surrounding the use of DOAC analogs in these patient cohorts and suggests the need for follow-up confirmatory systematic studies in this group of patients.

An original preoperative orthopaedic management of a complex spinal deformity in a 16-year-old patient with spondyloepiphyseal dysplasia congenita.

PURPOSE: Spinal deformities in patients with Spondyloepiphyseal Dysplasia congenita are particularly challenging to treat. Addressing these deformities requires a holistic surgical strategy. The aim of this case report is to highlight an original preoperative protocol combining atlantoaxial instability stabilization by halo jacket with progressive correction of a thoracic kyphoscoliosis using continuous elongation by tension plaster cast as described by Stagnara. METHOD: A 16-year-old patient with spondyloepiphyseal dysplasia congenita presenting a severe thoracic kyphoscoliosis associated with atlantoaxial instability causing cervical myelopathy was managed through a preoperative protocol combining a halo jacket with a Stagnara elongation cast allowing progressive correction of the kyphoscoliosis while stabilizing the cervical instability. RESULTS: The preoperative protocol allowed a safer and a more effective surgical spine fusion, reducing neurological risks, improving the final correction, and offering better postoperative recovery. Clinical and radiological solid fusion was observed at 3-year-follow-up with significant improvement of the patient's quality of life. CONCLUSION: This case report highlights the effectiveness of the preoperative preparation combining a halo jacket with a Stagnara elongation cast to safely stabilize the cervical spine while correcting the thoracic kyphoscoliosis. This strategy can serve as a valuable tool for spine teams when addressing complex spinal deformities particularly in this patient with SEDc. LEVEL OF EVIDENCE: Level IV.

Seroconversion and safety of Covid-19 vaccines in pa-tients with chronic liver disease and liver transplant: A systematic review.

BACKGROUND AND AIMS: As part of the COVID-19 control strategy, a growing number of vaccine portfolios evolved and got fast-tracked through regulatory agencies, with a limited examination of their efficacy and safety in vulnerable populations, such as patients with chronic conditions and immunocompromised states. Patients with chronic liver disease (CLD), and cohorts post liver transplant (LT) in particular, were underrepresented in the determinant trials of vaccine development, hence the paucity of data on their efficacy and safety in published literature. This systematic review aims to examine the available evidence and ascertain the effectiveness and safety of Covid-19 vaccination in patients with CLD and those with LT. METHODS: A systematic review of PubMed (Medline), Google Scholar, Cochrane Library, and ScienceDirect from inception until 1st March 2022 was conducted. We included observational studies and assessed vaccine efficacy regarding seroconversion or immunological rate, whereas serious or significant adverse effects have been considered safety outcomes when reported. RESULTS: Studies comprised 45275 patients, performed in 11 different countries. Seroconversion or immunological rate after Covid-19 vaccination was mostly the primary endpoint, whereas other endpoints like covid-19 related adverse effects were also reported. Twenty-four of the final analyzed studies are prospective cohort studies, while four are retrospective cohort studies. Twenty-one studies included patients who underwent LT and received the Covid vaccine; nine included patients who had CLD due to various etiologies. The median age range of all included patients varied from 43-69 years. All patients with LT who received at least two doses of Covid vaccine had a seroconversion rate of around 60%. Patients with CLD had a seroconversion rate of about 92% post two doses of Covid vaccination. The average seroconversion rate in post-transplant recipients was around 45% after two doses of the significant Covid vaccines: Pfizer, AstraZeneca, Moderna, and Jansen. Only two studies have reported a higher seroconversion rate of 75% and 73% after the third dose of Covid vaccine. No significant adverse effects were reported in all studies; the most commonly reported negative effect was local injection site pain. CONCLUSION: The present systematic review, comprising real-world observational data studies, concludes that Covid-19 vaccination was associated with 92% and 60% seroconversion rates in patients with CLD and LT, respectively. No significant side effects were reported in all studies. This finding helps to resolve the uncertainty associated with Covid-19 vaccination in this cohort of patients.

Synthetic non-toxic anti-biofilm agents as a strategy in combating bacterial resistance.

The tremendous increase in the bacterial resistance to the available antibiotics is a serious problem for the treatment of various infections. Biofilm formation in bacteria significantly contributes to the bacterial survival in host cells, and is considered as an crucial factor, responsible for bacterial resistance. The response of the bacterial cells in the biofilm to antibiotics is completely different from that of the free floating planktonic cells of the same strain. The anti-biofilm agents that could inhibit the biofilm production without affecting the bacterial growth, apply less selective pressure over the bacterial strains than the traditional antibiotics; thus the development of bacterial resistance would be of low incidence. Many attempts have been performed to discover novel agents capable of interfering with the bacterial biofilm life cycle, and several compounds have shown promising activities in suppressing the biofilm production or in dispersing mature existing biofilms. This review describes the different chemical classes that have anti-biofilm effects against different Gram-positive and Gram-negative bacteria without affecting the bacterial growth.

Phytochemical and metabolic profiling of the different Podocarpus species in Egypt: Potential antimicrobial and antiproliferative activities.

Podocarpus is the most dominant genus of Podocarpaceae, with higher taxonomical proximity to the Taxaceae, having numerous pharmaceutical applications, however, scarce studies dealing with the physiological and metabolic criteria of Podocarpus in Egypt were reported. Thus, the objective of this work was to assess the physiological and metabolical patterns of the different species of Podocarpus; P. gracilior, P. elongates, P. macrophyllus and P. neriifolius. The highest terpenoids contents were reported in P. neriifolius, followed by P. elongatus, and P. macrophyllus. P. gracilior had the highest antioxidants amount, followed by P. macrophyllus, P. neriifolius and P. elongatus. From the GC/MS metabolic profiling, caryophyllene, ß-cadinene, ß-cuvebene, vitispirane, ß-cadinene and amorphene were the most dominant metabolites in P. gracilior. ß-Caryophyllene was the common in P. gracilior, P. elongatus, P. macrophyllus and P. neriifolius with an obvious fluctuation. The plant methanolic extracts have an obvious activity against the multidrug resistant bacteria; E. coli, P. aeruginosa, S. pyogenes and S. aureus, and fungi; A. fumigatus, A. flavus, A. niger and C. albicans in a concentration-dependent manner. The highest Taxol yield was assessed in the extracts of P. elongatus (16.4 µg/gdw), followed by P. macrophyllus, and P. neriifolius. The chemical identity of Taxol derived from P. elongatus was resolved by LC/MS, with molecular mass 854.6 m/z, and similar structural fragmentation pattern of the authentic one. The highest antitumor activity of P. elongatus extracted Taxol was assessed towards HCT-116 (30.2 µg/ml), HepG-2 (53.7 µg/ml) and MCF-7 (71.8 µg/ml). The ITS sequence of P. elongatus "as potent Taxol producer" was deposited on Genbank with accession #ON540734.1, that is the first record of Podocarpus species on Genbank.

Case report: Exome sequencing revealed disease-causing variants in a patient with spondylospinal thoracic dysostosis.

Background: Spondylocostal dysostosis is a rare genetic disorder caused by mutations in DLL3, MESP2, LFNG, HES7, TBX6, and RIPPLY2. A particular form of this disorder characterized by the association of spondylocostal dysostosis with multiple pterygia has been reported and called spondylospinal thoracic dysostosis. Both disorders affect the spine and ribs, leading to abnormal development of the spine. Spondylospinal thoracic dysostosis is a rare syndrome characterized by the association of multiple vertebral segmentation defects, thoracic cage deformity, and multiple pterygia. This syndrome can be considered a different form of the described spondylocostal dysostosis. However, no genetic testing has been conducted for this rare disorder so far. Methods: We report here the case of an 18-month-old female patient presenting the clinical and radiological features of spondylospinal thoracic dysostosis. To determine the underlying genetic etiology, whole exome sequencing (WES) and Sanger sequencing were performed. Results: Using WES, we identified a variant in the TPM2 gene c. 628C>T, already reported in the non-lethal form of multiple pterygium syndrome. In addition, following the analysis of WES data, using bioinformatic tools, for oligogenic diseases, we identified candidate modifier genes, CAP2 and ADCY6, that could impact the clinical manifestations. Conclusion: We showed a potential association between TPM2 and the uncommon spondylocostal dysostosis phenotype that would require further validation on larger cohort.

Reconstruction of isolated hypoplasia of the patella by a modified Galeazzi procedure: a case report.

BACKGROUND: Isolated Patellar Aplasia Hypoplasia is a very rare autosomal dominant disorder. Its treatment depends on the clinical manifestations that can vary widely. The lack of active extension, which can be responsible for frequent falls due to a knee instability, is the most frequent and disabling manifestation. We report an original technique that is a modification of the Galeazzi technique for recurrent dislocation of the patella to gain active extension in case of PTLAH. CASE REPORT: A 7-year-old Caucasian boy with isolated Patellar Aplasia Hypoplasia and an extension lag of the right knee has been treated by a modified Galeazzi technique. The tendons of the semi-tendinous and gracilis muscles have been harvested and their distal insertion was kept intact. Both tendons were fixed over the top of the patella to restore knee active extension. After 6 years of follow up the patient is symptom free with a strong active extension of the operated knee. CONCLUSION: Reconstruction of isolated hypoplasia of the patella by a modified Galeazzi procedure is a safe and reliable technique for skeletally immature patients offering satisfying long-term outcomes.

Toxoplasma gondii Suppresses Th2-Induced by Trichinella spiralis Infection and Downregulates Serine Protease Genes Expression: A Critical Role in Vaccine Development.

Background: Toxoplasma gondii coinfection can modify host immune responses and the severity and spread of other parasites. We investigated how T. gondii and Trichinella spiralis infections counter-regulate each other's immune responses. Methods: The parasite burden, the expression of T. gondii rhoptry kinase ROP18 and T. spiralis putative serine protease (TsSP), the IgG1 and IgG2a responses, besides histopathological and immunohistochemical staining with iNOS and arginase were used to evaluate the dynamics of coinfection. Results: Through their effects on host immune responsiveness, coinfection with T. gondii modified the virulence of T. spiralis infection. Coinfected animals with high and low doses of T. gondii demonstrated significant reductions in the T. spiralis burden of 75.2% and 68.2%, respectively. TsSP expression was downregulated in both groups by 96.2% and 86.7%, whereasROP18 expression was downregulated by only 6% and10.6%, respectively. In coinfected mice, elevated levels of T. gondii-specific IgG2a antibodies were detected. Th1 induced by T. gondii inhibits the Th2 response to T. spiralis in coinfected animals with high iNOS expression andlow-arginine1 expression. Conclusion: T. gondii infection induces a shift toward a Th1-type immune response while suppressing a helminth-specific Th2 immune response, paving the way for developing novel vaccines and more efficient control strategies.

Comparing biological and physical cost functions in VMAT planning for pediatric nasopharyngeal cancer.

BACKGROUND: Volumetric Modulated Arc Therapy (VMAT) is an option for the delivery of Radiotherapy treatment technique for pediatric nasopharyngeal cancer, VMAT is the most common treatment technique for pediatric nasopharyngeal cancer. The use of a combination of both biological and physical parameters in VMAT planning optimization may produce better target coverage and sparing of critical organs. This work was to compare Biological Cost Functions (BCFs) and Physical Cost Functions (PCFs) in the VMAT of pediatric nasopharyngeal cancer patients. METHOD: VMAT plans for 20 nasopharyngeal pediatric cancer patients were created using Monaco 5.11® treatment planning system (TPS). Three VMAT plans were retrospectively generated for each patient using BCFs, PCFs and mixed plan with a total dose of 61.2 Gy in 34 fractions to planning target volume (PTV). All plans were adjusted to deliver 95% of the prescribed dose to 95% of the PTV. The calculated plans were qualitatively and quantitatively evaluated using the dose-volume histogram (DVH). RESULTS: The coverage of the target and the maximum dose for the three plans were nearly the same, and better sparing was achieved in the serial organs (spinal cord and brain stem) with PCFs. On the contrary, more dose spring was observed using the BCFs in the organs at risk (OARs) that were not involved in the dose optimization, such as the optic nerve maximum dose, with a significant p-value (0.035 and 0.0001) respectively. Using the PCFs, both parotids received a lower mean dose, but not for the oral cavity, which had a lower mean dose using BCFs (p=<0.0001). The same values of tumor control probability (TCP) were found for both cost functions in PTVs and normal tissue complications probability (NTCP) (99%). The values reported were as follows: spinal cord = 0.5%, brain stem = 19.1%, and brain = 90.7% for BCFs, compared to spinal cord = 0.3%, brain stem = 14.9%, and brain = 90.7% for PCFs. The delivery time was found to be less in BCFs (p=0.005). CONCLUSION: The BCFs are superior to the PCFs in conformity index and time of radiation delivery. However, PCFs were better at dose sparing for the serial organs and achieving a sharper falloff dose around the involved volumes. A patient-specific clinical compromise is recommended to gain the best plan that meets the clinical goals.

Effects of surfactant head group modification on vertically oriented mesoporous silica produced by the electrochemically assisted surfactant assembly method.

Production of mesoporous silica films with vertically oriented pores has been a challenge since interest in such systems developed in the 1990s. Vertical orientation can be achieved by the electrochemically assisted surfactant assembly (EASA) method using cationic surfactants such as cetyltrimethylammonium bromide (C16TAB). The synthesis of porous silicas using a series of surfactants with increasing head sizes is described, from octadecyltrimethylammonium bromide (C18TAB) to octadecyltriethylammonium bromide (C18TEAB). These increase pore size, but the degree of hexagonal order in the vertically aligned pores reduces as the number of ethyl groups increases. Pore accessibility is also reduced with the larger head groups.