Implications of Microorganisms in Alzheimer's Disease.

Alzheimer's disease (AD) is a deadly brain degenerative disorder that leads to brain shrinkage and dementia. AD is manifested with hyperphosphorylated tau protein levels and amyloid beta (Aß) peptide buildup in the hippocampus and cortex regions of the brain. The nervous tissue of AD patients also contains fungal proteins and DNA which are linked to bacterial infections, suggesting that polymicrobial infections also occur in the brains of those with AD. Both immunohistochemistry and next-generation sequencing (NGS) techniques were employed to assess fungal and bacterial infections in the brain tissue of AD patients and non-AD controls, with the most prevalent fungus genera detected in AD patients being Alternaria, Botrytis, Candida, and Malassezia. Interestingly, Fusarium was the most common genus detected in the control group. Both AD patients and controls were also detectable for Proteobacteria, followed by Firmicutes, Actinobacteria, and Bacteroides for bacterial infection. At the family level, Burkholderiaceae and Staphylococcaceae exhibited higher levels in the brains of those with AD than the brains of the control group. Accordingly, there is thought to be a viscous cycle of uncontrolled neuroinflammation and neurodegeneration in the brain, caused by agents such as the herpes simplex virus type 1 (HSV1), Chlamydophilapneumonia, and Spirochetes, and the presence of apolipoprotein E4 (APOE4), which is associated with an increased proinflammatory response in the immune system. Systemic proinflammatory cytokines are produced by microorganisms such as Cytomegalovirus, Helicobacter pylori, and those related to periodontal infections. These can then cross the blood-brain barrier (BBB) and lead to the onset of dementia. Here, we reviewed the relationship between the etiology of AD and microorganisms (such as bacterial pathogens, Herpesviridae viruses, and periodontal pathogens) according to the evidence available to understand the pathogenesis of AD. These findings might guide a targeted anti-inflammatory therapeutic approach to AD.

Combined aortic and mitral valvular surgery with the Intuity rapid deployment prosthesis in the aortic position: Operative tips and tricks.

The Edwards Intuity valve is a rapid deployment prosthesis designed for the aortic position. There is a paucity of literature on the use of the Intuity valve in combined aortic and mitral double valvular surgery. We present a case that highlights our novel surgical technique for implanting the Intuity valve in the aortic position following insertion of a conventional sutured bioprosthetic valve in the mitral position.

Novel use of the Perceval sutureless bioprosthesis for pulmonary valve replacement in high-risk endocarditis patients: A case series.

We present the first known cases of successful implantation of the Perceval sutureless bioprosthetic valve in the pulmonary position in two high-risk endocarditis patients.

Long-term durability of a Perceval aortic valve implanted inside a calcified homograft root in a patient with Klippel-Trenaunay-Weber syndrome.

BACKGROUND AND AIMS: Perceval valves are sutureless surgical bioprostheses designed for the aortic position. We report on the use of a Perceval sutureless valve for redo aortic valve replacement inside a heavily calcified homograft root in a patient with Klippel-Trenaunay-Weber syndrome. MATERIALS AND METHODS: Anonymized patient case data was extracted from hospital electronic records. RESULTS: A now 62-year-old woman with Klippel-Trenaunay-Weber syndrome underwent homograft aortic root replacement for congenital aortic valve dysplasia when she was 39 years old. She re-presented in 2012 with severe symptomatic aortic regurgitation through the homograft root. Computed tomography scanning revealed a heavily calcified homograft root. In order to avoid a high-risk redo root replacement or a challenging sutured aortic valve replacement, she underwent Perceval sutureless aortic valve implantation. As of 9.5 years following Perceval implantation, the bioprosthetic valve function remains excellent, with no transvalvular regurgitation seen. DISCUSSION AND CONCLUSION: This case reveals the value of Perceval valve implantation in redo surgery inside a hostile calcified homograft aortic root. Furthermore, we highlight the long-term durability of the Perceval sutureless bioprosthesis.

Multivessel coronary artery vasospasm masquerading as surgical coronary atherosclerotic disease.

BACKGROUND AND AIM: We report a case of a 39-year-old lady presenting with worsening angina. MATERIALS AND METHODS: This is a case report study. Clinical case data was retrieved from hospital paper and electronic records. RESULTS: Invasive coronary angiography revealed disease in the left main stem, proximal left anterior descending (LAD) artery and circumflex artery. The patient proceeded to on-pump coronary artery bypass grafting. Intraoperatively, there were multiple unsuccessful attempts to wean off cardiopulmonary bypass. An on-table angiogram-which initially triggered asystole requiring internal cardiac massage and institution of venoarterial extracorporeal membrane oxygenation (ECMO)- showed no native coronary artery disease. Instead, this angiogram revealed severe vasospasm with narrowing in the grafts and distal LAD. The patient received calcium channel blockers and bilateral thoracic sympathectomies to suppress any further coronary vasospasm. She was subsequently successfully weaned off ECMO. DISCUSSION AND CONCLUSION: This case reveals the life-threatening nature and diagnostic dilemma posed by severe multivessel coronary vasospasm. We also highlight the novel role of thoracic sympathectomy for definitive management of refractory vasospastic angina.

Ruptured giant left anterior descending coronary artery pseudoaneurysm.

We report a rare case of a ruptured giant left anterior descending coronary artery pseudoaneurysm that necessitated salvage operative repair. This case affirms the life-threatening nature of this clinically significant pathology, as well as the need for emergent repair before pseudoaneurysm rupture to maximize the likelihood of patient survival.

Complex redo surgery to treat a large thymoma invading the right atrium.

BACKGROUND AND AIM: Anterior mediastinal masses which invade the great vessels and heart are rare. We report a case of a 76-year-old male presenting with a large invasive anterior mediastinal mass following recent cardiac surgery (coronary artery bypass grafting and aortic valve replacement via sternotomy). MATERIALS AND METHODS: This is a case report study with clinical patient information retrieved from hospital electronic records. RESULTS: Computed tomography scanning revealed a large heterogeneous 6.5 × 7.2 × 7.0 cm right anterior mediastinal mass. The mass directly propagated via the left innominate vein into the superior vena cava (SVC) and proximal right atrium. The patient underwent redo sternotomy with the aid of cardiopulmonary bypass and hypothermic circulatory arrest to remove the mass. The mass was sitting in the right pleural cavity and was adherent to the right lung and pericardium. Tumor material was removed from the right atrium, SVC and left innominate vein. The mass was excised en bloc along with a portion of the upper lobe of the right lung. DISCUSSION AND CONCLUSION: Histology of the mass revealed the diagnosis of invasive type A thymoma with transvenous and transcardiac invasion. We advocate for surgeons to be aggressive in their operative resection of such tumours to ensure the best prognostic outlook for the patient.

Characteristics and Outcomes of Patients With Severe Aortic Stenosis Discussed by the Multidisciplinary "Heart Team" According to Treatment Allocation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an alternative and effective contemporary intervention to surgical aortic valve replacement (SAVR) for patients with severe aortic valve disease at increased surgical risk. Guidelines recommend a multidisciplinary "Heart Team" (MHT) review of patients considered for a TAVI procedure, but this has been little studied. We reviewed the characteristics, treatments and outcomes of such patients reviewed by the MHT at our centre. METHODS: Data on consecutive patients with severe aortic valve stenosis discussed by the Auckland City Hospital MHT from June 2011 to August 2016 were obtained from clinical records. Patient characteristics, treatment and outcomes were analysed using standard statistical methods. RESULTS: Over the 5-year period 243 patients (mean age 80.2 ± 8.0 years, 60% male) were presented at the MHT meeting. TAVI was recommended for 200, SAVR for 26 and medical therapy for 17 patients, with no significant difference in mean age (80.2 ± 8.3, 80.4 ± 6.1, 80.4 ± 7.3 years, respectively) or EuroSCORE II (6.5 ± 4.7%, 5.3 ± 3.6%, 6.7 ± 4.3%, respectively). Over time, there was an increase in the number of patients discussed and treated, with no change in their mean age, but the mean EuroSCORE II significantly decreased (TAVI p = 0.026, SAVR p = 0.004). Survival after TAVI and SAVR was similar to that of the age-matched general population, but superior to medical therapy p = 0.002 (93% (n = 162), 84% (n = 21) and 73% (n = 18) at one year and 85% (n = 149), 84% (n = 21) and 54% (n = 13) at 2 years, respectively). CONCLUSIONS: An increasing number of patients were discussed at the MHT meeting with the majority undergoing TAVI, with a similar age and EuroSCORE II to those allocated SAVR or medical therapy. Survival following TAVI and SAVR was superior to medical therapy and similar to the age-matched general population. These findings suggest that the MHT process is robust, consistent and appropriately allocating a limited treatment resource.

Nuclear factor-kappa ß as a therapeutic target for Alzheimer's disease.

Alzheimer's disease (AD) is a typical progressive, chronic neurodegenerative disorder with worldwide prevalence. Its clinical manifestation involves the presence of extracellular plaques and intracellular neurofibrillary tangles (NFTs). NFTs occur in brain tissues as a result of both Aß agglomeration and Tau phosphorylation. Although there is no known cure for AD, research into possible cures and treatment options continues using cell-cultures and model animals/organisms. The nuclear factor-kappa ß (NF-κß) plays an active role in the progression of AD. Impairment to this signaling module triggers undesirable phenotypic changes such as neuroinflammation, activation of microglia, oxidative stress related complications, and apoptotic cell death. These imbalances further lead to homeostatic abnormalities in the brain or in initial stages of AD essentially pushing normal neurons toward the degeneration process. Interestingly, the role of NF-κß signaling associated receptor-interacting protein kinase is currently observed in apoptotic and necrotic cell death, and has been reported in brains. Conversely, the NF-κß signaling pathway has also been reported to be involved in normal brain functioning. This pathway plays a crucial role in maintaining synaptic plasticity and balancing between learning and memory. Since any impairment in the pathways associated with NF-κß signaling causes altered neuronal dynamics, neurotherapeutics using compounds including, antioxidants, bioflavonoids, and non-steroidal anti-inflammatory drugs against such abnormalities offer possibilities to rectify aberrant excitatory neuronal activity in AD. In this review, we have provided an extensive overview of the crucial role of NF-κß signaling in normal brain homeostasis. We have also thoroughly outlined several established pathomechanisms associated with NF-κß pathways in AD, along with their respective therapeutic approaches.

Severe cardiomyopathy caused by a critically stenosed anomalous left coronary artery ostium originating in the left ventricle.

We report a case of a 44-year-old patient presenting with new-onset severe decompensated congestive heart failure, which was refractory to aggressive inpatient medical treatment. Left ventricular ejection fraction was 16%. Radiological investigations revealed the presence of an anomalous subannular origin of the left coronary artery, with an associated 95% ostial stenosis. The artery was supplied by collaterals from the right coronary system. This included a proximal collateral from the right marginal artery, which had its own separate ostium in the right aortic sinus. A diagnosis of ischemic dilated cardiomyopathy was made. The patient successfully underwent urgent coronary artery bypass grafting with a view to improve his left ventricular function and congestive heart failure symptoms.

Transcatheter Aortic Valve Implantation In Patients With a Large Aortic Annulus.

BACKGROUND: As the indications for transcatheter aortic valve implantation (TAVI) have expanded, so to have the demands on interventionists to allow as many patients to access this technology as possible. METHODS: We retrospectively reviewed our TAVI database for patients who had received a 29mm SAPIEN 3 valve despite having an annular area greater than the manufacturer-recommended upper limit of 683mm2, as determined by multi-detector computed tomography (MDCT). Procedural and inpatient outcome data were collected. RESULTS: The study population was 5 of 121 patients receiving a SAPIEN 3 valve since it became available in March 2015. Their annular area ranged from 691 to 800mm2. Valve deployment was successful in all patients. The deployment balloon volume was nominal, except for an additional 1ml in one patient. No patient had a new indication for permanent pacing, and no significant valvular or paravalvular regurgitation (PVR) was identified on post-procedure transthoracic echocardiography. All patients survived to hospital discharge. CONCLUSIONS: In this select group of patients we have demonstrated that it is safe and feasible to use the 29mm SAPIEN 3 in patients with annular dimensions greater than those recommended, with minimal balloon overfilling.

Brachial arterial temperature as an indicator of core temperature: proof of concept and potential applications.

There is potential for heat loss and hypothermia during anesthesia and also for hyperthermia if heat conservation and active warming measures are not accurately titrated. Accurate temperature monitoring is particularly important in procedures in which the patient is actively cooled and then rewarmed such as during cardiopulmonary bypass surgery (CPB). We simultaneously measured core, nasopharyngeal, and brachial artery temperatures to investigate the last named as a potential peripheral temperature monitoring site. Ten patients undergoing hypothermic CPB were instrumented for simultaneous monitoring of temperatures in the pulmonary artery (PA), aortic arterial inflow (AI), nasopharynx (NP), and brachial artery (BA). Core temperature was defined as PA temperature before and after CPB and the AI temperature during CPB. Mean deviations of BA and NP temperatures from core temperature were calculated for three steady-state periods (before, during, and after CPB). Mean deviation of BA and NP temperatures from AI temperature was also calculated during active rewarming. A total of 1862 measurements were obtained and logged from eight patients. Mean BA and NP deviations from core temperature across the steady-state periods (before, during, and after CBP) were, respectively: .23 +/- .25, -.26 +/- .3, and -.09 +/- .05 degrees C (BA), and .11 +/- .19, -.1 +/- .47, and -.04 +/- .3 degrees C (NP). During steady-state periods, there was no evidence of a difference between the mean BA and NP deviation. During active rewarming, the mean difference between the BA and AI temperatures was .14 +/- .36 degrees C. During this period, NP temperature lagged behind AI and BA temperatures by up to 41 minutes and was up to 5.3 degres C lower than BA (mean difference between BA and NP temperatures was 1.22 +/- .58 degrees C). The BA temperature is an adequate surrogate for core temperature. It also accurately tracks the changing AI temperature during rewarming and is therefore potentially useful in detecting a hyperthermic perfusate, which might cause cerebral hyperthermia.

Novel DLSNNC and SBS based framework for improving QoS in healthcare-IoT applications.

Health care system is intended to enhance one's health and as a result, one's quality of life. In order to fulfil its social commitment, health care must focus on producing social profit to sustain itself. Also, due to ever increasing demand of healthcare sector, there is drastic rise in the amount of patient data that is produced and needs to be stored for long duration for clinical reference. The risk of patient data being lost due to a data centre failure can be minimized by including a fog layer into the cloud computing architecture. Furthermore, the burden of such data produced is stored on the cloud. In order to increase service quality, we introduce fog computing based on deep learning sigmoid-based neural network clustering (DLSNNC) and score-based scheduling (SBS). Fog computing begins by collecting and storing healthcare data on the cloud layer, using data collected through sensors. Deep learning sigmoid based neural network clustering and score based Scheduling approaches are used to determine entropy for each fog node in the fog layer. Sensors collect data and send it to the fog layer, while the cloud computing tier is responsible for monitoring the healthcare system. The exploratory findings show promising results in terms of end-to-end latency and network utilization. Also, the proposed system outperforms the existing techniques in terms of average delay.

Epigenetic factors in breast cancer therapy.

Epigenetic modifications are inherited differences in cellular phenotypes, such as cell gene expression alterations, that occur during somatic cell divisions (also, in rare circumstances, in germ line transmission), but no alterations to the DNA sequence are involved. Histone alterations, polycomb/trithorax associated proteins, short non-coding or short RNAs, long non-coding RNAs (lncRNAs), & DNA methylation are just a few biological processes involved in epigenetic events. These various modifications are intricately linked. The transcriptional potential of genes is closely conditioned by epigenetic control, which is crucial in normal growth and development. Epigenetic mechanisms transmit genomic adaptation to an environment, resulting in a specific phenotype. The purpose of this systematic review is to glance at the roles of Estrogen signalling, polycomb/trithorax associated proteins, DNA methylation in breast cancer progression, as well as epigenetic mechanisms in breast cancer therapy, with an emphasis on functionality, regulatory factors, therapeutic value, and future challenges.

Quantum dots: The cutting-edge nanotheranostics in brain cancer management.

Quantum dots (QDs) are semiconductor nanocrystals possessing unique optoelectrical properties in that they can emit light energy of specific tunable wavelengths when excited by photons. They are gaining attention nowadays owing to their all-around ability to allow high-quality bio-imaging along with targeted drug delivery. The most lethal central nervous system (CNS) disorders are brain cancers or malignant brain tumors. CNS is guarded by the blood-brain barrier which poses a selective blockade toward drug delivery into the brain. QDs have displayed strong potential to deliver therapeutic agents into the brain successfully. Their bio-imaging capability due to photoluminescence and specific targeting ability through the attachment of ligand biomolecules make them preferable clinical tools for coming times. Biocompatible QDs are emerging as nanotheranostic tools to identify/diagnose and selectively kill cancer cells. The current review focuses on QDs and associated nanoformulations as potential futuristic clinical aids in the continuous battle against brain cancer.

Therapeutic Potential of Green Synthesized Metallic Nanoparticles Against Staphylococcus aureus.

BACKGROUND: The recent treatment challenges posed by the widespread emergence of pathogenic multidrug-resistant (MDR) bacterial strains cause huge health problems worldwide. Infections caused by MDR organisms are associated with longer periods of hospitalization, increased mortality, and inflated healthcare costs. Staphylococcus aureus is one of these MDR organisms identified as an urgent threat to human health by the World Health Organization. Infections caused by S. aureus may range from simple cutaneous infestations to life-threatening bacteremia. S. aureus infections easily escalate in severely ill, hospitalized, and or immunocompromised patients with an incapacitated immune system. Also, in HIV-positive patients, S. aureus ranks amongst one of the most common comorbidities where it can further worsen a patient's health condition. At present, anti-staphylococcal therapy is typically reliant on chemotherapeutics that are gaining resistance and pose unfavorable side-effects. Thus, newer drugs are required that can bridge these shortcomings and aid effective control against S. aureus. OBJECTIVE: In this review, we summarize drug resistance exhibited by S. aureus, lacunae in current anti-staphylococcal therapy and nanoparticles as an alternative therapeutic modality. The focus lies on various green synthesized nanoparticles, their mode of action, and their application as potent antibacterial compounds against S. aureus. CONCLUSION: The use of nanoparticles as anti-bacterial drugs has gained momentum in the recent past, and green synthesized nanoparticles, which involve microorganisms and plants or their byproducts for the synthesis of nanoparticles, offer a potent, as well as environment friendly solution in warfare against MDR bacteria.

miRNAs in SARS-CoV 2: A Spoke in the Wheel of Pathogenesis.

INTRODUCTION: The rapid emergence of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-- CoV-2) has resulted in an increased mortality rate across the globe. However, the underlying mechanism of SARS-CoV-2 altering human immune response is still elusive. The existing literature on miRNA mediated pathogenesis of RNA virus viz. Dengue virus, West Nile virus, etc. raises a suspicion that miRNA encoded by SARS-CoV-2 might facilitate virus replication and regulate the host's gene expression at the post-transcriptional level. METHODS: We investigated this possibility via computational prediction of putative miRNAs encoded by the SARS-CoV-2 genome using a novel systematic pipeline that predicts putative mature-miRNA and their targeted genes transcripts. To trace down if viral-miRNAs targeted the genes critical to the immune pathway, we assessed whether mature miRNA transcripts exhibit effective hybridization with the 3'UTR region of human gene transcripts. Conversely, we also tried to study human miRNA-mediated viral gene regulation to get insight into the miRNA mediated offense and defense mechanism of virus and its host organisms in toto. RESULTS: Our analysis led us to shortlist six putative miRNAs that target, majorly, genes related to cell proliferation/ differentiation/signaling, and senescence. Nonetheless, they also target immune-related genes that directly/ indirectly orchestrate immune pathways like TNF (Tumor Necrosis Factor) signaling and Chemokine signaling pathways putatively serving as the nucleus to cytokine storms. CONCLUSION: Besides, these six miRNAs were found to be conserved so far across 80 complete genomes of SARS-CoV-2 (NCBI Virus, last assessed 12 April 2020) including Indian strains that are also targeted by 7 human miRNAs and can, therefore, be exploited to develop MicroRNA-Attenuated Vaccines.

Fostering mesenchymal stem cell therapy to halt cytokine storm in COVID-19.

The coronavirus disease 2019 (COVID-19) has been threatening the globe since the end of November 2019. The disease revealed cracks in the health care system as health care providers across the world were left without guidelines on definitive usage of pharmaceutical agents or vaccines. The World Health Organization (WHO) declared COVID-19 as a pandemic on the 11th of March 2020. Individuals with underlying systemic disorders have reported complications, such as cytokine storms, when infected with the virus. As the number of positive cases and the death toll across the globe continue to rise, various researchers have turned to cell based therapy using stem cells to combat COVID-19. The field of stem cells and regenerative medicine has provided a paradigm shift in treating a disease with minimally invasive techniques that provides maximal clinical and functional outcome for patients. With the available evidence of immunomodulatory and immune-privilege actions, mesenchymal stem cells (MSCs) can repair, regenerate and remodulate the native homeostasis of pulmonary parenchyma with improved pulmonary compliance. This article revolves around the usage of novel MSCs therapy for combating COVID-19.

Advances in pulmonary drug delivery targeting microbial biofilms in respiratory diseases.

The increasing burden of respiratory diseases caused by microbial infections poses an immense threat to global health. This review focuses on the various types of biofilms that affect the respiratory system and cause pulmonary infections, specifically bacterial biofilms. The article also sheds light on the current strategies employed for the treatment of such pulmonary infection-causing biofilms. The potential of nanocarriers as an effective treatment modality for pulmonary infections is discussed, along with the challenges faced during treatment and the measures that may be implemented to overcome these. Understanding the primary approaches of treatment against biofilm infection and applications of drug-delivery systems that employ nanoparticle-based approaches in the disruption of biofilms are of utmost interest which may guide scientists to explore the vistas of biofilm research while determining suitable treatment modalities for pulmonary respiratory infections.

Acute ischaemic ventricular septal defect--a formidable surgical challenge.

BACKGROUND: To evaluate our surgical results for Acute Ischaemic Ventricular Septal Defect and suggest practice guidelines. METHODS: Retrospective review of data from patient records between 1992 and 2006 for presentation, surgical approaches, morbidity and mortality, statistically analysed to derive guidelines for management. RESULTS: We had 36 patients with a mean age of 70.44(+/-6.34) years. Fourteen patients had inferior defects. Twenty-eight patients were in shock (22 on pre-operative IABP). Severe LV and RV dysfunction were present in 18 and 20 patients respectively. At surgery, 17 had infarct resection with patching while 18 had repair with infarct exclusion. Concomitant CABG was performed in 15. One patient was re-operated on for mitral valve replacement and one for recurrent VSD. Recurrent VSD was common (11 patients). Two of these patients underwent percutaneous device closure of whom one died. Prolonged ICU and hospital stay was normal. Early mortality was 52.78% (inferior defects-85.71% and anterior defects-31.82%). Inferior VSD (OR 7.7) and pre-operative shock (OR 6.7), predicted mortality. The subgroup of inferior VSD with shock had mortality equating that with medical management published in literature. CONCLUSIONS: Acute Ischaemic VSD is a grim surgical disease marked by residual shunts and high mortality. Patients with inferior defects with shock should be offered surgery only under exceptional circumstances.