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Coronary artery anomalies, myocardial bridging associated with fistula to pulmonary artery trunk. Case reports
No full textBetween coronary artery anomalies, myocardial bridging means an epicardial coronary artery, mostly left anterior descending artery (LAD), running through an intramyocardial “tunnel” (usually in the middle segment), leading during systolic contraction, flow reduction, through the vessel. When this anomaly is associated with a coronary fistula, which “steals” more from the bloodstream, the symptoms are more pronounced, and the management complex is surgical in particular. Despite the presence from birth remains asymptomatic and it becomes clinically manifest later in the third to fourth decade of life, with a diverse palette of symptoms; angina, arrhythmias, and acute myocardial infarction up to sudden death. Diagnosis and particular management, medical, interventional, and surgical should avoid major cardiac complications and sudden death. We present two adult patients, with coronary artery bridging, one case associated with coronary artery fistula, LAD to pulmonary artery trunk, very symptomatic with surgical management, and the second only myocardial bridging controlled with medication and supervision
Design and optimization of mRNAs encoding an Anti-TIGIT antibody with therapeutic potential for cancer in TIGIT-humanized BALB/c Mice
No full textmRNA drugs are synthesized using cell-free systems without complex and stringent manufacturing processes, which makes their preparation simple, efficient, and economical. Over the past few years, mRNAs encoding antibodies have been one of the research frontiers of antibody drug development. In cancer immunotherapy, mRNAs encoding immune checkpoint antibodies may be advantageous regarding antibody persistence and durability of the anti-tumor immune response of patients. In our previous study, a candidate antibody—AET2010—targeting the novel immune checkpoint TIGIT was reported. Its anti-tumor activity was also investigated using adoptive transfer of NK-92MI cells in a xenograft mouse model, but the limitations of the model did not facilitate precise evaluation. In the present study, we further investigated the therapeutic potential of AET2010 for cancer in TIGIT-humanized BALB/c mice. Next, we explored the design, synthesis, and optimization of mRNAs encoding AET2010 and ultimately obtained a candidate mRNA (mRNA-BU) with favorable in vitro and in vivo expression levels of active AET2010. Particularly, lipid-nanoparticle-encapsulated mRNA-BU delivered to mice produced AET2010 with significantly higher peak concentration and expression duration than an equivalent dose of original AET2010. This study provides a sound basis for developing novel drugs targeting TIGIT
Expanding human-based predictive models capabilities using organs-on-chip: A standardized framework to transfer and co-culture human iPSCs into microfluidic devices
No full textThere is an urgent need for predictive preclinical models to enhance the success rate of clinical trial outcomes. One of the main reasons for drug attrition is the lack of translational models, methods using human cells are particularly in the spotlight of regulatory bodies as they offer an alternative to in vivo studies and have the potential to improve the translational of preclinical trials. Organs-on-Chips (OoCs) are sensible candidates to reduce the cost and the ethical burden of animal models while accelerating and de-risking drug development. The innovation of such systems is based on both the increased relevance of the cells used and the ability to build precise, yet physiologically relevant, complex architectures. The use of microfluidic technologies with human induced pluripotent stem cells (hiPSCs) opens new routes to create relevant in vitro approaches as they will soon be able to reproduce clinical characteristics of donors or specific populations. The adoption of OoC models by pharmaceutical industries, and in fine by regulatory agencies, still requires: (i) establishing standardized, reproducible, robust, and replicable cell culture protocols with specific validation and characterization criteria, (ii) evidence that the technology predicts human responses, thus allowing to contribute efficiently and reliably to clinical trials success of novel therapeutics, and (iii) evidence that the models refine and reduce animal testing without compromising with the quality and the pertinence of the data generated
Anterolateral ligament: A case report
No full textThe Anterolateral Ligament (ALL) [1,2] is a ligamentous structure of the knee whose definition as a ligament has been disputed in the past, however in the last decade more and more anatomical studies have concluded that its definition as a separate ligament is the most accurate. In this case report we present our findings from the dissection of a formalinized cadaver which we find are consistent with the anatomical characteristics of the anterolateral ligament and with that we aim to further its morphological definition
Adjusted Hardy-Rogers-Type Result Generalization
No full textThe adjusted Hardy-Rogers result generalization for the fixed point is demonstrated in this study, validating our results utilizing an application
Models for Long-Term Care Policy: What the U.S. Can Learn from Other Countries
No full textThe need to provide Long-Term Care (LTC) for growing elderly populations is a public policy issue in all industrialized countries. Unlike other OECD countries, the U.S. lacks a foundation for universal LTC benefits. Much can be learned by examining other industrialized countries. LTC systems. In this paper, we will examine how other countries' provide LTC services for their glowing elderly populations, finance the costs of LTC services, determine eligibility for services, and encourage and support informal caregivers
An Innovative Therapy by Changing the Gut Microbiome for the Dual Post-Operative Complications of the Recurrent Methicillin-Resistant Staphylococcus aureus (MRSA) Infections in the Residual Type II First Branchial Cyst and Facial Nerve Palsy
No full textA very unusual, interesting, and challenging case of a 24-year-old female who was born with three openings in the neck. The patient had chronic abdominal gaseous distention, recurrent abdominal pain, and constipation since early infancy. The patient presented in emergency with acute painful red, hot, and tender swelling in the left upper cervical area. Laboratory studies showed high inflammatory markers and a provisional diagnosis of abscess with a sinus was made. The patient underwent an emergency incision and drainage. Sinus recurred and a sinogram showed it to be a residual cyst in the left submandibular salivary gland. The total cyst excision was attempted with resultant recurrence and grade IV facial nerve palsy. Post-operatively recurrent infections caused by Methicillin-resistant Staphylococcus aureus (MRSA) required several courses of oral and intravenous broad-spectrum antibiotics with several hospital admissions with no resolution in sight. Subsequent ultrasound and magnetic resonance imaging showed a residual infected cyst, cutaneous sinus, and a fistula opening in the left ear canal. A diagnosis of branchial cyst type II of the first brachial cleft remnant with a fistula was established with bilateral branchial fistulas of the second branchial remnants and the associated colorectal hypoganglionosis based on radiological studies. The patient refused any further operative interventions. Therefore, the option of conservative treatment of hypoganglionosis with holobiotics consisting of prebiotics, probiotics and postbiotics, laxatives, dietary changes, lifestyle modifications, and dietary supplements started. All antibiotics were stopped. These therapies resulted in the resolution of residual first branchial remnants and recurrent MRSA infections with the improvement in the facial nerve palsy from grade V to grade III-IV together with an excellent cosmetic and functional result. The patient is doing well at follow-ups being infection-free for 18 months and repeat contrast-enhanced computed tomogram (CECT) has shown complete resolution of the residual cyst, sinus, and fistula with fibrosis
Osseous Choristoma with in a Dermolipoma: 17 Years Old Girl Case Report
No full textBone choristoma within a dermolipoma is a rare epibulbar tumor with a low prevalence. It is a benign tumor that does not usually cause discomfort or functional problems to patients who suffer from it. Its treatment is surgical and with an aesthetic purpose.We report the case of a 17-year-old patient with a bone choristoma, a tooth, within a dermolipoma.Epibulbar bone choristoma is a rare benign tumor that causes little discomfort to patients who suffer from it and is asymptomatic in most cases. Computed tomography (CT) is essential in its diagnosis and its treatment is surgical, but always due to aesthetic reasons
To Examine the Effects of Risk Factors Associated with Kidney Stones in Determining the Disease by Considering their Combinations
No full textAim: Kidney stone disease, which can affect people of all ages and whose incidence increases day by day, is becoming a public health problem due to treatment costs. This study aims to determine how factors related to kidney stones affect the diagnosis of the disease when taken together, rather than determining their relationship with the disease one by one.Materials and methods: An open-access dataset containing kidney stone status and associated factors was used in the study. Mann Whitney U test and independent sample t-test were used in data analysis. Logistic regression was performed with the backward variable selection method to determine the factors associated with kidney stones. ROC analysis was used to determine the power of the variables that were significant as a result of logistic regression analysis, individually and together, in discriminating kidney stones.Results: According to the results of logistic regression analysis, gravity, cond, and urea calc variables were found to be associated with kidney stones. With ROC analysis, it can be said that urea, calc, and gravity variables with AUC values above 0.60 can distinguish kidney stones. When the combinations of these variables are examined, the AUC values of the binary combinations are between 0.734 and 0.759, while the AUC value obtained for the triple combination is 0.831.Conclusion: According to the results obtained from the article, it can be said that while the factors associated with the disease and used in the diagnosis have little effect on the diagnosis of the disease alone based on the AUC values obtained from the ROC analysis, it can be said that considering them together increases the accuracy in diagnosis. Therefore, considering the factors thought to be associated with the disease together may be more appropriate in diagnosis and may give more accurate results
‘Life-Changing Bubbles’ – How carbonated water can relieve swallowing problems for many dysphagia sufferers worldwide
No full textToday, there are said to be some 590 million people of all ages around the world, who are suffering from a range of swallowing problems – probably about 4 million in the UK. Either living at home or as residents in some 20,000 Care Homes, with perhaps another 25,000 as patients in hospitals every day.Professor David Smithard, of the Lewisham and Greenwich NHS Trust, has been leading a national campaign for some years to raise general awareness of Dysphagia and to improve the treatment of patients with varying conditions. He and his team at the Queen Elizabeth Hospital have now completed a detailed Review of the use of carbonated water (CW) in the treatment of Dysphagia, which has just been published and can be accessed here: https://www.mdpi.com/2308-3417/8/1/6The Review concludes that further evidence-based research is essential before CW can be adopted as standard in clinical practice – but that although the amount of evidence is small, there is a suggestion that swallows are safer and that secretion management improves, and consequently until further studies are undertaken, Carbonated Water should be limited to individual patient use.My experience as a Dysphagia sufferer is that the use of CW has resulted in life-changing benefits, and this paper is devoted to describing how CW worked for me, and what the practical requirements are, so that many others may be able to benefit as I have done. The paper has three sections: My Personal Experience, Practical Considerations, and Conclusions