Short structural variants as informative genetic markers for ALS disease risk and progression

There is considerable variability in disease progression for patients with amyotrophic lateral sclerosis (ALS) including the age of disease onset, site of disease onset, and survival time. There is growing evidence that short structural variations (SSVs) residing in frequently overlooked genomic regions can contribute to complex disease mechanisms and can explain, in part, the phenotypic variability in ALS patients. Here, we discuss SSVs recently characterized by our laboratory and how these discoveries integrate into the current literature on ALS, particularly in the context of application to future clinical trials. These markers may help to identify and differentiate patients for clinical trials that have a similar ALS disease mechanism(s), thereby reducing the impact of participant heterogeneity. As evidence accumulates for the genetic markers discovered in SQSTM1, SCAF4, and STMN2, we hope to improve the outcomes of future ALS clinical trials.

Marine Organisms as Alkaloid Biosynthesizers of Potential Anti-Alzheimer Agents

The incidence of neurodegenerative diseases, such as Alzheimer’s disease (AD), increases continuously demanding the urgent development of anti-Alzheimer’s agents. Marine organisms (MO) have to create their own defenses due to the adverse environment where they live and so synthesize several classes of compounds, such as akaloids, to defend themselves. Therefore, the identification of marine natural products with neuroprotective effects is a necessity. Being that AD is not only a genetic but also an environmental complex disease, a treatment for AD remains to discover. As the major clinical indications (CI) of AD are extracellular plaques formed by β-amyloid (Aβ) protein, intracellular neurofibrillary tangles (NFTs) formed by hyper phosphorylated τ-protein, uncommon inflammatory response and neuron apoptosis and death caused by oxidative stress, alkaloids that may decrease CI, might be used against AD. Most of the alkalolids with those properties are derivatives of the amino acid tryptophan mainly with a planar indole scaffold. Certainly, alkaloids targeting more than one CI, multitarget-directed ligands (MTDL), have the potential to become a lead in AD treatment. Alkaloids to have a maximum of activity against CI, should be planar and contain halogens and amine quaternization.

Hybrid coronary revascularization in multivessel coronary artery disease: a systematic review

Aim: Hybrid coronary revascularization (HCR) for multivessel coronary artery disease (CAD) integrates coronary artery bypass grafting (CABG) and percutaneous intervention in a planned revascularization strategy. This systematic review summarizes the state of this art of this technique. Methods: Major databases searched until October 2021. Results: The available literature on HCR includes three randomized trials, ten meta-analysis and 27 retrospective studies. The greatest benefits are observed in patients with low-to-intermediate risk and less complex coronary anatomy; highly complex disease and the presence of risk factors favored conventional CABG in terms of adverse events and survival. Conclusion: HCR is an interesting approach for multivessel CAD but should not be considered a ‘one-size-fits-all’ procedure. Further studies will specify the subset of patients likely to benefit most from this hybrid approach.

L’infermiere e la percezione del Moral Distress nella cura del fine vita nel paziente dializzato

The phenomenon of Moral Distress in nursing practice is described as a situation of suffering that arises when the nurse recognizes the ethically appropriate action to be taken and yet institutional impediments make it impossible for him to follow the right course of action. Dialysis patients often have a complex disease trajectory that sometimes involves professional and emotional challenges for staff, especially at the end of life. The objective of this review is to identify which strategies are useful for preserving emotional integrity and awareness in operational settings, for the benefit of both operators and patients.

First report of Avian metapneumovirus type B in Iraqi broiler flocks with swollen head syndrome

Background and Aim: Swollen head syndrome (SHS) is a complex disease caused by various agents, including bacterial and viral pathogens, as well as environmental factors. Avian metapneumovirus (aMPV) is one of the most important causes of respiratory diseases and SHS in poultry and one of the most widespread viruses worldwide; however, it has not been recorded in Iraq. This study aimed at the molecular identification and subtyping of aMPV in poultry, with the objectives of investigating the prevalence of aMPV in infected broiler flocks with SHS and molecular typing using primers specific to the study of the prevalence of subtypes A, B, and C of aMPV. Materials and Methods: This study was performed on 67 broiler farms that reported typical SHS from September 2018 to August 2019. Swabs were collected from the trachea, infraorbital sinuses, and lung, then uploaded on FTA cards and subjected to an RNA extraction protocol. Results: aMPV was detected in 16 (23.8%) samples. Molecular typing using primers specific to the attachment glycoprotein (G) gene showed that all positive samples belonged to subtype B, as assessed using the real-time polymerase chain reaction technique. Conclusion: aMPV may be the main etiological factor causing SHS in poultry. Moreover, this was the first report of the prevalence of subtype B aMPV strains in broiler farms in Iraq.

Quality Control of Mitochondria in Parkinson's Disease (PD) Using ATP And Bradford Assays

Parkinson's disease is a heterogeneous, multifactorial and often complex disease characterized by motor impairment due to the presence of Lewy bodies and prominent degeneration of dopaminergic neurons in the substantia nigra. Although the specific pathogenesis involving PD remains under investigation, mitochondrial dysfunction has been widely accepted as one of the major pathogenic pathways underlying the development of PD. Based on the hypothesis that depiction of HtrA2 (serine protease gene, mitochondrial precursor) might contribute to an increase in mitochondrial stress and transcriptional upregulation of the nuclear stress-response CHOP gene. The present study aimed to analyze through laboratory-based research the role of HtrA2 and CHOP in the transmission of stress signaling and the consequent activation of mitochondrial quality control in Parkinson's disease using ATP and Bradford assays.

Melatonin drugs inhibit SARS-CoV-2 entry into the brain and virus-induced damage of cerebral small vessels

COVID-19 is a complex disease with short- and long-term respiratory, inflammatory and neurological symptoms that are triggered by the infection with SARS-CoV-2. Invasion of the brain by SARS-CoV-2 has been observed in humans and is postulated to be involved in post COVID condition. Brain infection is particularly pronounced in the K18-hACE2 mouse model of COVID-19. Here, we show that treatment of K18-hACE2 mice with melatonin and two melatonin-derived marketed drugs, agomelatine and ramelteon, prevent SARS-CoV-2 entry in the brain thereby reducing virus-induced damage of small cerebral vessels, immune cell infiltration and brain inflammation. Brain entry of SARS-CoV-2 through endothelial cells is prevented by melatonin through allosteric binding to human angiotensin-converting enzyme 2 (ACE2), which interferes with the cell entry receptor function of ACE2 for SARS-CoV-2. Our findings open new perspectives for the repurposing of melatonergic drugs in the prevention of brain infection by SARS-CoV-2 and COVID-19-related long-term neurological symptoms.

At a Glance: An Update on Neuroimaging and Retinal Imaging in Alzheimer’s Disease and Related Research

Neuroimaging serves a variety of purposes in Alzheimer’s disease (AD) and related dementias (ADRD) research - from measuring microscale neural activity at the subcellular level, to broad topological patterns seen across macroscale-brain networks, and everything in between. In vivo imaging provides insight into the brain’s structure, function, and molecular architecture across numerous scales of resolution; allowing examination of the morphological, functional, and pathological changes that occurs in patients across different AD stages (1). AD is a complex and potentially heterogenous disease, with no proven cure and no single risk factor to isolate and measure, whilst known risk factors do not fully account for the risk of developing this disease (2). Since the 1990’s, technological advancements in neuroimaging have allowed us to visualise the wide organisational structure of the brain (3) and later developments led to capturing information of brain ‘functionality’, as well as the visualisation and measurement of the aggregation and accumulation of AD-related pathology. Thus, in vivo brain imaging has and will continue to be an instrumental tool in clinical research, mainly in the pre-clinical disease stages, aimed at elucidating the biological complex processes and interactions underpinning the onset and progression of cognitive decline and dementia. The growing societal burden of AD/ADRD means that there has never been a greater need, nor a better time, to use such powerful and sensitive tools to aid our understanding of this undoubtedly complex disease. It is by consolidating and reflecting on these imaging advancements and developing long-term strategies across different disciplines, that we can move closer to our goal of dementia prevention. This short commentary will outline recent developments in neuroimaging in the field of AD and dementia by first describing the historical context of AD classification and the introduction of AD imaging biomarkers, followed by some examples of significant recent developments in neuroimaging methods and technologies.

Outcomes of eosinophilic esophagitis in patients managed in a multidisciplinary clinic

Background: Eosinophilic esophagitis is a complex disease with an increasing prevalence. Multidisciplinary teams are often needed to manage this difficult-to-treat condition. Objective: To observe the clinical and histologic outcomes of patients with eosinophilic esophagitis after management in a multidisciplinary clinic. Methods: An observational, retrospective chart review was conducted to include all patients referred to the Walter Reed National Military Medical Center multidisciplinary eosinophilic esophagitis clinic between August 2012 and February 2021. Only patients who had at least one esophagogastroduodenoscopy before referral, one or more visits and endoscopy after multidisciplinary management, and documented clinical symptoms were included. Statistical analysis was performed by using McNemar and Wilcoxon tests. Results: A total of 103 patients were included in the study, with a mean age at diagnosis of 17.9 years. Management in the multidisciplinary clinic was associated with a reduction in solid-food dysphagia by 70.9%, poor growth by 70.8%, and emesis or regurgitation by 87.5%. We observed that 48.5% and 62.1% had histologic remission (<15 eosinophils/hpf) on the initial and any post-multidisciplinary endoscopy, respectively. Only seven patients (5.8%) with two or more visits and endoscopies did not achieve histologic remission. More than two-thirds of the patients (68.9%) required combination therapy to achieve remission. Conclusion: Although an observational study, these findings may suggest that the management of patients with eosinophilic esophagitis in a multidisciplinary clinic may improve the likelihood of clinical and histologic remission. Targeted management with a multidisciplinary approach may reduce overall morbidity and slow disease progression; however, more research is needed.

Serum Ferritin Concentration in Corona Virus Disease 19

Introduction: Coronavirus disease 19 (COVID-19) is a complex disease responsible for the development of exacerbated inflammatory response (cytokine storm) that ultimately leads to multiorgan failure and death. Serum ferritin has been recently identified as one of the inflammatory markers responsible for the pro-inflammatory effects. Small amount of ferritin is present in plasma (15-150 ng/mL) which might increase with the severity of COVID-19. Therefore, measurement of ferritin is essential in identifying disease severity and predict disease prognosis. Objective: This study aims to assess the ferritin level in COVID-19 patients. Methods: A cross-sectional study was carried out on 259 COVID-19 patients visiting KIST Medical College and Teaching Hospital (KISTMCTH), Lalitpur, Nepal from November 2020 to April 2021. Serum ferritin was estimated in the automated Siemens ADVIA Centaur CP Chemiluminescence Immunoassay system. All the patients visiting KISTMCTH referred by clinician for ferritin assessment were included in this study. Data collected using the proforma tool was tabulated in SPSS 21 and statistical analysis was done by inferential statistical test. Results: Out of total 259 COVID-19 patients, 58.7% were male and the majority of patients (82.6%) were below 70 years of age. The mean age for all participants was 52.11±16.59 years. Hyperferritinemia was seen in 218 (84.16%) COVID -19 patients. The mean value of serum ferritin was 767.1±789.86 (IQR: 12.8-4590) ng/mL and was significantly higher in males (p<0.001). Comparing the mean values of ferritin between the patients below and above 70 years, no statistical difference was observed (p=0.872). Conclusions: In our study, serum ferritin levels were greatly increased in patients with COVID-19 infection. Keywords: Coronavirus disease 19; cytokine storm; inflammatory marker; serum ferritin.