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Background: Phenylketonuria is an autosomal recessive disorder characterized by accumulation of phenylalanine in blood and body fluids that is caused by defective Phe hydroxylase activity. Aim of the present study is to assess lifestyle for children with phenylketonuria. Design: A descriptive design was used in this study. Setting: conducted at genetic counseling clinic in basic health care unit at El Fayoum affiliated to Ministry of Health (MOH). Sample: A purposive sample included all children with Phenylketonuria composed of 79 children accompanied by their mothers. Tools: structural interviewing questionnaire to assess demographic characteristics, and medical history, and lifestyle assessment Questionnaire for children with PKU to identify current strengths of child’s health, and risk factors. Results: (74.7%) of families were discovered the disease by Ministry of Health screening programs. (92.4%) of children were made regular follow up. (78.5%) of children had follow up visits once monthly. 89.9% of children were not Taking breast feeding 62% of mothers had inadequate knowledge about the relation between breast feeding and the disease process. Conclusion: There is a statistically significant correlation between compliance with the prescribed diet and growth problems. There is no statistically significant correlation between compliance with the prescribed diet and sleep problems. Recommendations: The current study recommended Periodic assessment of Children affected commitment to prescribed diet. Increase mother knowledge about the importance of prescribed diet for children with Phenylketonuria

Introduction: End stage renal disease (ESRD) has accompanying oral pathologies that emerge from the disease process or from the impact of hemodialysis or both. Inevitably, untreated oral lesions may aggravate clinical presentation and prognosis of renal disease. The aim of our study was to investigate the clinical patterns of white lesions in the oral cavity in the patients having end-stage renal disease, and to study the factors associated with the appearance of these lesions. Methods: A cross-sectional, descriptive and observational study was designed to determine prevalence of oral white lesions among patients with ESRD attending the nephrology hemodialysis department for more than six months at Qalyub Hospital in Qalyub, Al Qalyubia Governorate, Egypt. A total of 114 adult participants of both genders from 30 up to 60 years were included in the study. A salivary pH and salivary flow rate were estimated. Results: Oral white lesions were found among 33 patients out of 114 with a prevalence of 28.9 % in the studied sample of ESRD patients. The most common oral white lesions were oral candidiasis (11.4%), Lichen planus or lichenoid reaction lesions (10.5%) and oral keratotic lesions (6.1%), while the least oral white lesions were Leukoplakia (2.6%) and uremic stomatitis (2.6%). Conclusion: An association between the prevalence of oral candidiasis and the following (salivary pH, salivary flow rate) was found. Also an association between uremic stomatitis and the higher blood urea and higher serum creatinine level was found in our studied sample of the patients with ESRD.

Continued rise in incidence and prevalence of diabetes globally warrants an effective strategy for its prevention and control. Prevention of diabetes seems more logical to attempt seeing its health care burden, long dormancy, systemic affliction and poor general awareness. Pre-diabetes is the intermediate state of erratic glucose metabolism without overt features of diabetes. This state seems to be a crossroad having a possibility to either convert into clinical diabetes, remain dormant or return to normal glucose control depending upon the efforts made. Unfortunately, due to the paucity of apparent clinical symptoms, this state embedded with reversal possibility, remains unexplored. Ayurveda account of prameha purvarupa (subclinical features of diabetes) may be proposed as the foundation upon which clinic-based pre-diabetes identification and subsequent prevention may be explored. Knowing the symptoms for their reliable proximity with upcoming diabetes may turn to be sensible sensitizers prompting the people to abort the disease process in an effective and timely manner. Considering diabetes from its purvarupa to complications as disease continuum and exploring the opportunities to intervene in order to prevent, or manage the disease on the basis of shada kriyaa kaala therefore, has a huge translational potential warrants an urgent exploration.

Huntington disease (HD) is a single-gene autosomal dominant inherited neurodegenerative disease caused by a polyglutamine expansion of the protein huntingtin (HTT). Huntingtin-associated protein 1 (HAP1) is the first protein identified as an interacting partner of huntingtin, which is directly associated with HD. HAP1 is mainly expressed in the nervous system and is also found in the endocrine system and digestive system, and then involves in the occurrence of the related endocrine diseases, digestive system diseases, and cancer. Understanding the function of HAP1 could help elucidate the pathogenesis that HTT plays in the disease process. Therefore, this article attempts to summarize the latest research progress of the role of HAP1 and its application for diseases in recent years, aiming to clarify the functions of HAP1 and its interacting proteins, and provide new research ideas and new therapeutic targets for the treatment of cancer and related diseases.

Objectives Our discussant’s thoughtful consideration of the patient’s case allows for review of three maxims of medicine: Occam’s razor (the simplest diagnosis is the most likely to be correct), Hickam’s dictum (multiple disease entities are more likely than one), and Crabtree’s bludgeon (the tendency to make data fit to an explanation we hold dear). Case presentation A 66-year-old woman with a history of hypertension presented to our hospital one day after arrival to the United States from Guinea with chronic daily vomiting, unintentional weight loss and progressive shoulder pain. Her labs are notable for renal failure, nephrotic range proteinuria and normocytic anemia while her shoulder X-ray shows osseous resorption in the lateral right clavicle. Multiple myeloma became the team’s working diagnosis; however, a subsequent shoulder biopsy was consistent with follicular thyroid carcinoma. Imaging suggested the patient’s renal failure was more likely a result of a chronic, unrelated process. Conclusions It is tempting to bludgeon diagnostic possibilities into Occam’s razor. Presumption that a patient’s signs and symptoms are connected by one disease process often puts us at a cognitive advantage. However, atypical presentations, multiple disease processes, and unique populations often lend themselves more to Hickam’s dictum than to Occam’s razor. Diagnostic aids include performing a metacognitive checklist, engaging analytic thinking, and acknowledging the imperfections of these axioms.

Pancreatic ductal adenocarcinoma (PDAC) represents a challenging pathology with very poor outcomes and is increasing in incidence within the general population. The majority of patients are diagnosed incidentally with insidious symptoms and hence present late in the disease process. This significantly affects patient outcomes: the only cure is surgical resection but only up to 20% of patients present with resectable disease at the time of clinical presentation. The use of "omic" technology is expanding rapidly in the field of personalised medicine - using genomic, proteomic and metabolomic approaches allows researchers and clinicians to delve deep into the core molecular processes of this difficult disease. This review gives an overview of the current findings in PDAC using these "omic" approaches and summarises useful markers in aiding clinicians treating PDAC. Future strategies incorporating these findings and potential application of these methods are presented in this review article.

Introduction Identifying the course of Alzheimer's disease (AD) for individual patients is important for numerous clinical applications. Ideally, prognostic models should provide information about a range of clinical features across the entire disease process. Previously, we published a new comprehensive longitudinal model of AD progression with inputs/outputs covering 11 interconnected clinical measurement domains. Methods Here, we (1) validate the model on an independent cohort; and (2) demonstrate the model's utility in clinical applications by projecting changes in 6 of the 11 domains. Results Survival and prevalence curves for two representative outcomes-mortality and dependency-generated by the model accurately reproduced the observed curves both overall and for patients subdivided according to risk levels using an independent Cox model. Discussion The new model, validated here, effectively reproduces the observed course of AD from an initial visit assessment, allowing users to project coordinated developments for individual patients of multiple disease features.

This overview of progress made in preventing post-traumatic osteoarthritis (PTOA) was delivered in a workshop at the Orthopaedics Research Society Annual Conference in 2019. As joint trauma is a major risk factor for OA, defining the molecular changes within the joint at the time of injury may enable the targeting of biological processes to prevent later disease. Animal models have been used to test therapeutic targets to prevent PTOA. A review of drug treatments for PTOA in rodents and rabbits between 2016 and 2018 revealed 11 systemic interventions, 5 repeated intra-articular or topical interventions, and 5 short-term intra-articular interventions, which reduced total Osteoarthritis Research Society International scores by 30%-50%, 20%-70%, and 0%-40%, respectively. Standardized study design, reporting of effect size, and quality metrics, alongside a "whole joint" approach to assessing efficacy, would improve the translation of promising new drugs. A roadblock to translating preclinical discoveries has been the lack of guidelines on the design and conduct of human trials to prevent PTOA. An international workshop addressing this in 2016 considered inclusion criteria and study design, and advocated the use of experimental medicine studies to triage candidate treatments and the development of early biological and imaging biomarkers. Human trials for the prevention of PTOA have tested anakinra after anterior cruciate ligament rupture and dexamethasone after radiocarpal injury. PTOA offers a unique opportunity for defining early mechanisms of OA to target therapeutically. Progress in trial design and high-quality preclinical research, and allegiance with patients, regulatory bodies, and the pharmaceutical industry, will advance this field.

The enteric nervous system plays a critical role in the regulation of gastrointestinal tract functions and is often referred to as the 'second brain' because it shares many features with the central nervous system. These similarities include among others a large panel of neurotransmitters, a large population of glial cells and a susceptibility to neurodegeneration. This close homology between the central and enteric nervous systems suggests that a disease process affecting the central nervous system could also involve its enteric counterpart. This was already documented in Parkinson's disease, the most common synucleinopathy, in which alpha-synuclein deposits are reported in the enteric nervous system in the vast majority of patients. Tau is another key protein involved in neurodegenerative disorders of the brain. Whether changes in tau also occur in the enteric nervous system during gut or brain disorders has just begun to be explored. The scope of the present article is therefore to review existing studies on the expression and phosphorylation pattern of tau in the enteric nervous system under physiological and pathological conditions and to discuss the possible occurrence of 'enteric tauopathies'.

Osteoarthritis (OA) is a progressive disease and OA pain intensity is related to ongoing pathophysiological changes. However, OA pain is complex and multimodal; its characteristics, including severity, localization and the stimuli that elicit it, can change as the disease progresses and differ greatly among patients. Understanding mechanisms underlying specific pain characteristics may help guide clinicians in choosing appropriate treatments, targeting treatments to those patients most likely to benefit. Associations have been demonstrated between biomarkers and some characteristics of OA pain, and to processes linked to the shift in pain characteristics over the course of OA. This article examines how understanding OA pain characteristics and their relation to the disease process could inform treatment choice when applying well-established treatment guidelines.

Objective: The Coronavirus Disease-2019 (COVID-19) pandemic continues to be a concern, especially to people with chronic diseases across the entire world During this pandemic, we undertook an investigation to assess how the disease state and medical treatments of inflammatory bowel disease (IBD) are affecting the IBD patients, their risky perceptions, as well as the frequency and course of COVID-19 Methods: During the pandemic, the information on the course of the disease, medical treatment status of the patients with IBD, and the course of the disease in IBD patients who had COVID-19 were collected via telephonic interview Results: A total of 102 IBD patients, including 62 with ulcerative colitis and 40 with Crohn's disease were included in the study Of these, 52 9% of the patients believed that having IBD was a risk for COVID-19 During the pandemic, 18 6% of the patients did not take their medication regularly for various reasons Of all, 64 28% of the patients with active disease could not go to the hospital to avoid the risk of acquiring COVID-19 and 4 90% acquired COVID-19 Conclusion: During the pandemic, both the regular consumption of medicines and the reservations regarding admission to hospitals affect the course of IBD Therefore, the development of strategic action plans to support and manage changes experienced during the course of this disease is expected to facilitate the management of the disease process in a healthier way for both the physicians and the patients [ABSTRACT FROM AUTHOR] Copyright of European Archives of Medical Research is the property of Galenos Yayinevi Tic LTD STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all Abstracts )

With increasing subspecialised experience in radical cytoreductive surgery and intra-abdominal chemotherapy for peritoneal malignancy, outcomes have improved significantly in selected patients. The surgery and the treatment regimens are radical and therefore correct patient selection is critical. The radiologist plays a central role in this process by estimating, as precisely as possible, the pre-treatment disease burden. Because of the nature of the disease process, accurate staging is not an easy task. Tumour deposits may be very small and in locations where they are very difficult to detect. It must be acknowledged that no form of modern day imaging has the capability of detecting the smallest peritoneal nodules, which may only be visible to direct inspection or histopathological evaluation. Nonetheless, it behoves the radiologist to be as exact and precise as possible in the reporting of this disease process. This is both to select patients who are likely to benefit from radical treatment, and just as importantly, to identify patients who are unlikely to achieve adequate cytoreductive outcomes. In this review, we outline the patterns of spread of disease and the anatomic basis for this, as well as the essential aspects of reporting abdominal studies in this patient group. We provide an evidence-based update on the relative strengths and limitations of our available multimodality imaging techniques namely CT, MRI and positron emission tomography/CT.

Growing evidence has suggested an association between sleep duration and Alzheimer's disease (AD), but it is unclear if sleep duration is a manifestation of the AD disease process. We studied whether genetic liability for AD predicts sleep duration using a genetic risk score (GRS) for AD (AD-GRS), in 406,536 UK Biobank participants with European ancestry and without dementia at enrollment. Higher AD-GRS score was associated with shorter sleep (b = -0.014, 95% confidence interval [CI] = -0.022 to -0.006), especially in those aged 55+. Using AD-GRS as an instrumental variable for AD diagnosis, incipient AD reduced sleep duration by 1.87 hours (95% CI = 0.96, 2.78). Short sleep duration might be an early marker of AD. ANN NEUROL 2021;89:177-181.

Objectives To present historical and contemporary hypotheses on the pathogenesis of benign prostatic hyperplasia (BPH), and the potential implications for current medical therapies. Methods The literature on BPH was reviewed. BPH is a prevalent disease with significant health and economic impacts on patients and health organisations across the world, whilst the cause/initiation of the disease process has still not been fully determined. Results In BPH, pathways involving androgens, oestrogens, insulin, inflammation, proliferative reawakening, stem cells and telomerase have been hypothesised in the pathogenesis of the disease. A number of pathways first described >40 years ago have been first rebuked and then have come back into favour. A system of an inflammatory process within the prostate, which leads to growth factor production, stem cell activation, and cellular proliferation encompassing a number of pathways, is currently in vogue. This review also highlights the physiology of the prostate cell subpopulations and how this may account for the delay/failure in treatment response for certain medical therapies. Conclusion BPH is an important disease, and as the pathogenesis is not fully understood it impacts the effectiveness of medical therapies. This impacts patients, with further research potentially highlighting novel therapeutic avenues.

The COVID-19 pandemic has been a global crisis at an unprecedented level. More than 4.75 million cases and 157,000 deaths have been reported in the U.S. as of August 3, 2020. The whole disease process, from symptoms and diagnosis to medications and treatment, has been a challenge, as COVID-19 is a novel disease that the world has never before encountered. In this article, the authors discuss the disease symptoms, pathophysiology and treatments based on their experience treating COVID-19 positive patients in the intensive care units of a major Louisiana academic medical center.

Peptide receptor radionuclide therapy (PRRT), over the years, has evolved as an important modality in the therapeutic armamentarium of advanced, metastatic or inoperable, progressive Neuroendocrine Neoplasms (NENs). This review deliberates on the basic understanding and applied clinical aspects of PRRT in NENs, with special reference to (1) tumor biology and receptor characteristics, (2) molecular PET-CT imaging (in particular the invaluable role of dual-tracer PET with [68Ga]-DOTA-TATE/NOC and [18F]-FDG for exploring tumor biology in continuum and individualizing treatment decision making) and NEN theranostics, (3) relevant radiochemistry of different therapeutic radionuclides (both beta emitting 177Lu-DOTATATE and 90Y-DOTATATE and alpha emitting 225Ac-DOTATATE), and (4) related dosimetric considerations. Successful clinical management of the NENs would require multifactorial considerations, and all the aforementioned points pertaining to the disease process and available logistics are key considerations for state-of-the-art clinical practice and delivering personalized care in this group of patients. Emphasis has been placed on relatively intriguing areas such as (1) NET grade 3 of WHO 2017 classification (ie, Ki-67>20% but well-differentiation features), (2) "Neoadjuvant PRRT," (3) combining chemotherapy and PRRT, (4) 'Sandwich Chemo-PRRT', (5) duo-PRRT and tandem PRRT, (6) resistant functioning disease with nuances in clinical management and how one can advocate PRRT rationally in such clinical settings and individualize the management in a patient specific manner. Relevant clinical management issues related to some difficult case scenarios, which the Nuclear Medicine attending physician should be aware of to run an efficient clinical PRRT services, are described.

In a clinical trial, people with the same disease can show different responses after treatment with the same drug and exactly under the same conditions. Some of them may improve, some may not show any response, and occasionally side effects may be observed. In other words, people with the same disease process under the same therapeutic conditions may have different responses. Today, some diseases are resistant to conventional (standard) treatment procedures. Why do people with the same disease show different responses to the treatment with the same drug? This is primarily due to differences in molecular pathways (especially genetic variations) associated with the disease. On the other hand, designing and delivery of a new drug is a time-consuming and costly process, so any mistake in any stage of this process can have irreparable consequences for pharmaceutical companies and consumer patients. Therefore, we can achieve more accurate and reliable treatments by acquiring precise insight into different aspects of precision medicine including genomics and transcriptomics. The aim of this paper is to address the role of genomics and transcriptomics in precision medicine.

Back ground- Inflammation has a decisive role in pathological classification of diseases in modern medicine and well-known phenomenon of infectious diseases and Non communicable disorders (NCD) also. Ayurveda emphasised the doshic involvement in pathophysiology of diseases process and the phenomenon of Sopha is undetermined in diagnosis and treatment. Objective- A literature survey from Ayurveda classical texts was undertaken to understand the role of Sopha in disease process. Methods- The enumerations of Sopha in Bruhatrayee, Madhav nidana & Bhela Samhita are critically studied to find out its etiology, types, pathogenesis and line of treatment. Enumeration- Sopha is very fundamental to understand the disease process in Ayurveda. The normal snigdha-sheet- agneya character of Srotas get disturbed by the Vidahi & Abhisandhya dravyas, as a result there is a disturbed in the transport mechanism of the affected Srotas. Sopha can be a symptom of any disease and/or an independent disease and may be a complication of other diseases. Sopha can be classified as Antah Sopha & Bahir Sopha. Discussion- The concept of sopha was discussed in terms of pathology and treatment of modern science. Conclusion- Sopha is linked with wide spectrum of Infectious as well as Non communicable disorders (NCD). This study also found out a range of therapies for Sopha driven diseases. It can be recommended to include this concept of Sopha in Ayurveda undergraduate and post graduate curriculum.

Recognition of the importance of nonmotor dysfunction as a component of Parkinson’s disease has exploded over the past three decades. Autonomic dysfunction is a frequent and particularly important nonmotor feature because of the broad clinical spectrum it covers. Cardiovascular, gastrointestinal, urinary, sexual, and thermoregulatory abnormalities all can appear in the setting of Parkinson’s disease. Cardiovascular dysfunction is characterized most prominently by orthostatic hypotension. Gastrointestinal dysfunction can involve virtually all levels of the gastrointestinal tract. Urinary dysfunction can entail either too frequent voiding or difficulty voiding. Sexual dysfunction is frequent and frustrating for both patient and partner. Alterations in sweating and body temperature are not widely recognized but often are present. Autonomic dysfunction can significantly and deleteriously impact quality of life for individuals with Parkinson’s disease. Because effective treatment for many aspects of autonomic dysfunction is available, it is vitally important that assessment of autonomic dysfunction be a regular component of the neurologic history and exam and that appropriate treatment be initiated and maintained. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-020-00897-4) contains supplementary material, which is available to authorized users.

Patients with Alzheimer's disease (AD) present with both extracellular amyloid-β (Aβ) plaques and intracellular tau-containing neurofibrillary tangles in the brain. For many years, the prevailing view of AD pathogenesis has been that changes in Aβ precipitate the disease process and initiate a deleterious cascade involving tau pathology and neurodegeneration. Beyond this 'triggering' function, it has been typically presumed that Aβ and tau act independently and in the absence of specific interaction. However, accumulating evidence now suggests otherwise and contends that both pathologies have synergistic effects. This could not only help explain negative results from anti-Aβ clinical trials but also suggest that trials directed solely at tau may need to be reconsidered. Here, drawing from extensive human and disease model data, we highlight the latest evidence base pertaining to the complex Aβ-tau interaction and underscore its crucial importance to elucidating disease pathogenesis and the design of next-generation AD therapeutic trials.

Laminitis is a devastating disease with diverse etiologies and few, if any, effective treatments. Gene expression and hypothesis-generating genomic studies have provided a fresh look at the key molecular players at crucial timepoints in diverse experimental and naturally affected tissues. We summarize findings to date, and propose a unifying model of the laminitis disease process that includes several pathogenesis concepts shared with other diseases of epidermal and epithelial tissues. The value of these new pathways as potential therapeutic targets is exciting but will require careful future work to validate new methods and launch systematic clinical trials.

Acute retinal necrosis is a rare yet devastating disease, with significant ocular morbidity. Over the past several decades, initial treatment regimens have shifted from intravenous antivirals requiring hospital admission to the routine use of oral antivirals with intravitreal antivirals for immediate local control. Given the rarity of this disease process and a lack of large-scale research trials, debate continues over recommended practice guidelines. In this paper, we review current diagnostic criteria and recommend a treatment algorithm based on available evidence.

There has long been a recognised association between non-alcoholic fatty liver disease (NAFLD) and the composite aspects of the metabolic syndrome. Part of this association highlighted the supposed co-existence of elevated uric acid levels in those with NAFLD. There is interest in exploitation of this as a putative diagnostic and prognostic biomarker in NAFLD. Given the increased economic and health burden associated with the NAFLD epidemic, improved methods of population-based, minimally-invasive methods and biomarkers are clearly highly sought and necessary. In this opinion review we review the proposed role of uric acid in the pathogenesis of NAFLD and its potential utilisation in the diagnosis and monitoring of the disease process.

Diabetes disrupts organs throughout the body including the brain. Evidence suggests diabetes is a risk factor for Alzheimer's disease (AD) and neurodegeneration. In this review, we focus on understanding how diabetes contributes to the progression of neurodegeneration by influencing several aspects of the disease process. We emphasize the potential roles of brain insulin resistance, as well as cholesterol and lipid disruption, as factors which worsen AD.

Chronic recurrent multifocal osteomyelitis (CRMO) is a pediatric autoinflammatory disorder that is characterized by multiple sterile inflammatory bone lesions with a relapsing and remitting course. CRMO belongs to the autoinflammatory family of rheumatologic disorders based on absence of significant titers of autoantibodies and autoreactive T-lymphocytes. In absence of pathognomonic clinical, radiographic or pathological features, diagnosis can be challenging. CRMO shares imaging features with other diseases. It is important for radiologists to be able to differentiate other diseases from CRMO because prognosis varies from completely benign to frankly malignant. In this article we first present the clinical and imaging features of CRMO to help readers gain an understanding of the disease process, then discuss our imaging approach to CRMO and review other disease processes that sometimes share similar imaging findings to CRMO and review differentiating features to help avoid misdiagnoses.

Outcome measurement is the definitive way to prove or disprove the usefulness of a procedure and its impact on a disease process. Cleft lip and palate is a disease with many facets and involvement of many subspecialties in its treatment. It is therefore necessary to have a comprehensive approach towards outcome measures for satisfactory treatment endpoint. Patient opinion even in case of children is very important and should actually form a very important component of overall outcome measures. Authors' experience in the Indian subcontinent shows that many children have been very happy with results that may be found wanting by some. In some cases that proved a boon for the child to grow in the world facing adversities. Authors' have proposed a simplified standard of points for outcome measures for uniformity of results.

The pandemic status of COVID-19 was recorded by the World Health Organization (WHO) on March 11, 2020 Since then, more than 10 million cases have been confirmed worldwide, with more than 500,000 reported deaths Throughout this period, efforts by the global scientific community have focused on understanding the disease process and searching on preventive (e g vaccines) or therapeutic (e g drugs) alternatives of treatment for COVID-19 The present review portrays the historical aspects associated with the discovery of SARS-CoV-2, the etiological agent of COVID-19, describes the pathophysiological aspects of the disease, the viral replication process and discusses the main molecular targets subject to therapeutic intervention, aiming the design, discovery and development of new drugs to treat COVID-19

The evolution of pluripotent stem cell-derived retinal organoids (ROs) has brought remarkable opportunities for developmental studies while also presenting new therapeutic avenues for retinal diseases. With a clear understanding of how well these models mimic native retinas, such preclinical models may be crucial tools that are widely used for the more efficient translation of studies into novel treatment strategies for retinal diseases. Genetic modifications or patient-derived ROs can allow these models to simulate the physical microenvironments of the actual disease process. However, we are currently at the beginning of the three-dimensional (3D) RO era, and a general quantitative technology for analyzing ROs derived from numerous differentiation protocols is still missing. Continued efforts to improve the efficiency and stability of differentiation, as well as understanding the disparity between the artificial retina and the native retina and advancing the current treatment strategies, will be essential in ensuring that these scientific advances can benefit patients with retinal disease. Herein, we briefly discuss RO differentiation protocols, the current applications of RO as a disease model and the treatments for retinal diseases by using RO modeling, to have a clear view of the role of current ROs in retinal development and diseases.

Osteoarthritis (OA) is a debilitating disease generally of old age manifested as degeneration of articular cartilage. With no definitive treatment available, ongoing research aims at early detection and use specific noninvasive imaging markers to monitor therapeutic efficacy of disease modifying osteoarthritic drug (DMOAD) to reverse or/and arrest the disease process. Articular cartilage degradation and loss, as well as bone remodelling, are typical biomarkers of OA. As a result, an ideal imaging technique for early detection of OA is required, which must be sensitive to both soft tissue and bone health. PET/MRI is emerging as an imaging tool which can be used to study the underlying pathogenesis of OA as it enables us to assess molecular activity with PET markers while also linking them to qualitative and quantitative MRI indices of OA. In this regard recent work was exploring the role of 18F–Na Fluoride which is a marker of bone remodelling together with MRI in early detection of OA on simultaneous PET/MRI. In this article we intend to present different patterns of OA (mild to severe stages of OA) that we had observed on 18F-Sodium Fluoride (18F–NaF) PET/MRI.

Articulating a satisfactory definition of a disease is surprisingly difficult. Despite the alarming individual, societal and economic burden of chronic obstructive pulmonary disease (COPD), diagnosis is still largely based on a physiologically dominated disease conception, with spirometrically determined airflow limitation as a cardinal feature of the disease. The diagnostic inaccuracy and insensitivity of this physiological disease definition is reviewed considering scientific developments of imaging of the respiratory system in particular. Disease must be approached as a fluid concept in response to new scientific and medical discoveries, but labelling as well as mislabelling someone as diseased, will have enormous individual, social and financial implications. Nosology of COPD urgently needs to dynamically integrate more sensitive diagnostic procedures to detect the breadth of abnormalities early in the disease process. Integration of broader information for the identification of abnormalities in the respiratory system is a cornerstone for research models of underlying pathomechanisms to create a breakthrough in research.

PURPOSE OF REVIEW: Chronic rhinosinusitis (CRS) is a highly prevalent disease with large social and financial burdens. The pathophysiology is multifactorial. Environmental pollutants have been suggested to play a role in the inflammatory component of the disease process. RECENT FINDINGS: Recent work has focused on exposure to various pollutants, primarily particulate matter (PM). Exposure to environmental pollutants leads to upregulation of inflammatory markers and ciliary dysfunction at the cellular level. Mouse models suggest a role for epithelial barrier dysfunction contributing to inflammatory changes after pollutant exposure. Clinical studies support the role of pollutants contributing to disease severity in certain populations, but the role in CRS incidence or prevalence is less clear. Research is limited by the retrospective nature of most studies. SUMMARY: This review focuses on recent advancements in our understanding of the impact of environmental pollutants in CRS, limitations of the available data, and potential opportunities for future studies.

Vulval Crohn's disease is a rare manifestation of Crohn's disease. Although it is usually caused by a fistulating process, it may be a result of a metastatic disease process as well, the exact mechanisms of which are not well understood yet. Vulval Crohn's disease may occur before the onset of bowel symptoms and may continue to be active while bowel symptoms are quiescent. Coupled with the fact that most vulval Crohn's lesions are similar to other disease processes, it can prove to be a diagnostic challenge. Due to its rarity, no guidelines for treatment exist; however, most reports agree that when symptoms are not controlled with antibiotics and topical steroids, immunosuppressive medications such as oral steroids and biological agents are the way forward. Although surgery may be an option, data suggest that its use is scarce. We report the case of a 47-year-old Caucasian woman with bilateral metastatic vulval Crohn's disease from a district hospital in the United Kingdom who responded well to ustekinumab. This is one of the first few cases reporting good clinical outcomes with the agent.

Sickle cell disease (SCD) is a group of inherited blood disorders affecting the hemoglobin, shortening the lifespan of erythrocytes, and causing them to take on a distinctive sickled shape that can lead to vaso-occlusion. Current treatment aims to reduce morbidity and mortality through hydroxyurea, erythrocyte transfusion, and hematopoietic stem cell transplantation. This article reviews the disease process, typical presentations, complications, and acute and chronic treatment options.

Research advancements to improve the accuracy of diagnosing Alzheimer's disease (AD) have altered clinicians and researchers’ understanding of the disease process. The discovery of amyloid and tau biomarkers as measures of disease pathology supports early identification of disease risk that precedes symptom onset. As a result, AD is now understood to be an underlying pathology that causes a spectrum of clinical syndromes, beginning with preclinical AD. Future clinical implementation of biomarkers will raise novel employment and professional licensure discrimination risks based on AD biomarker status. This article evaluates the potential consequences of biomarker status for commercial pilots within Federal Aviation Administration pilot licensing procedures. The article argues for a careful implementation of AD biomarker status in licensing procedures to emphasize public safety, integrate accurate scientific knowledge, and limit unjustified and adverse consequences for individual pilots.

The number of obese patients worldwide has more than doubled over the last 30 years. Changes in the locomotorium caused by obesity include degenerative and inflammatory lesions, and most often it is osteoarthrosis. Osteoarthrosis affects all aspects of life through pain and mobility limitations, therefore the problem of treating such patients remains relevant. Methods. Analysis of literature sources regarding the influence of obesity on osteoarthrosis development based on changes in the level of clinical and instrumental and diagnostic aspects. Results. Ostearthrosis is not just a disease of aging joints; it is rather caused by a process of metabolic disorders, during which various lipid, metabolic and humoral inflammatory mediators contribute to the initiation and progression of the disease process. Patients with obesity and osteoarthrosis, who are losing weight, may experience a reduction in the symptoms of osteoarthrosis. The authors note that weight loss in such patients is associated with a decrease in inflammatory factors such as C-reactive protein (CRP), tumor necrosis factor (TNF), and interleukin-6 (IL-6), which have been associated with physical function disorder.

Exacerbations are major events in the disease process in patients with chronic obstructive pulmonary disease (COPD). They have a negative effect on the quality of life and the progression of the disease. Frequent exacerbations are associated with increased mortality. In addition to the optimal therapy, the prevention of further exacerbations and the attention to concomitant diseases are prognostically crucial for the patients. In this review article, current recommendations for the diagnosis, therapy and follow-up care of COPD exacerbations are summarized.

High endemicity of Johne’s disease (JD) in herds adversely affects heavy milk yielding breeds by reducing the per animal productivity and ‘productive life-span’. This review evaluates different vaccines used for its control and summarizes the benefits of ‘global vaccine’ in the four major domestic livestock species, namely goat, sheep, buffalo and cattle. Vaccines developed by using ‘native strains’ revealed both 'therapeutic' and preventive effects in domestic livestock. The 'therapeutic' role of vaccine in animals suffering from clinical JD turned out to be valuable in some cases by reversing the disease process and animals returning back to health and production. Good herd management, improved hygiene, ‘test and cull’ methodology, proper disposal of animal excreta and monitoring of MAP bio-load were also regarded as crucial in the 'therapeutic' management of JD. Vaccine approaches have been widely adopted in JD control programs and may be considered as a valuable adjunct in order to utilize huge populations of otherwise un-productive livestock. It has been shown that vaccination was the preeminent strategy to control JD, because it yielded approximately 3–4 times better benefit-to-cost ratios than other strategies. Internationally, 146 vaccine trials/studies have been conducted in different countries for the control of JD and have shown remarkable reduction in its national prevalence. It is concluded that for JD, there cannot be global vaccines or diagnostic kits as solutions have to come from locally prevalent strains of MAP. Despite some limitations, vaccines might still be an effective strategy to reduce or eradicate JD.

We hypothesize that Parkinson’s disease (PD) pathogenesis can be divided into three temporal phases. During the first phase, “triggers”, such as viral infections or environmental toxins, spark the disease process in the brain and/or peripheral tissues. Triggers alone, however, may be insufficient, requiring “facilitators” like peripheral inflammation for PD pathology to develop. Once the disease manifests, “aggravators” spur further neurodegeneration and exacerbate symptoms. Aggravators are proposed to include impaired autophagy and cell-to-cell propagation of α-synuclein pathology. We believe clinical trials need to consider these three phases and target potential therapies at the appropriate stage of the disease process in order to be effective.

The surgical treatment of Parkinson's disease has made significant progress over the past 70 years; however, its scope of effectiveness remains limited to motor symptoms like bradykinesia, rigidity, tremor and medication-induced dyskinesias. The field of surgery initially developed from lesioning procedures and then transitioned largely to deep brain stimulation due to its properties of adaptability and reversibility. Interestingly, there has been a renewed interest in lesioning procedures secondary to the introduction of focused ultrasound, a non-invasive technology. Despite the various current therapies' effectiveness, there is a significant need for developing treatments to modify the disease process itself. To date, gene therapy, immunotherapy, and cell transplantation trials have had both promising and disappointing results. Newer techniques being developed (optogenetics, magnetogenetics, and sonogenetics) are exciting possibilities for the future. Here, we examine and speculate on novel potential surgical treatments for Parkinson's disease.

A better understanding of the pathophysiology and etiology of dry eye disease leads to more efficient management and treatment of the disease process. However, there is substantial variation among both clinicians and countries in terms of dry eye treatment modalities. The latest 2017 International Dry Eye Workshop II report aimed to reduce these differences and emphasized the use of a stepped care algorithm. The algorithm includes treatment forms ranging from artificial tear drops, the primary conventional treatment method, to the latest surgical applications. The aims of the algorithm are to restore homeostasis in the ocular surface, break the vicious cycle of inflammation, and ensure long-term ocular surface comfort.

This article describes the 6-year journey to diagnosis of twin girls with varying presentations of the same rare disease. Batten disease is a neurodegenerative disease caused by an autosomal recessive genetic mutation. In patients with juvenile Batten disease, the most common initial symptom is vision loss, and initial testing early in the disease process typically fails to find any indication of this fatal disease.

Immunoglobulin subclass 4 related disease (IgG4-RD) is an increasingly recognised autoimmune disease with the potential of affecting various organs. It has a predilection for certain anatomical hotspots and the pancreatobiliary tract is the the most common area involved. Due to the relative novelty of IgG4-RD, the understanding of the disease process continues to involve. Recent European guidelines on IgG4-RD have been published by a working group collaboration between the United European Gastroenterology and Swedish Society of Gastroenterology. In our commentary, we aim to extract the key practical points with an emphasis on diagnosis and management of IgG4-RD with specific focus on the pancreatobiliary tract.

Dental caries is an irreversible microbial disease of the calcified tissues of the teeth. It is a bacterial driven,generally chronic, site-specific, the multifunctional dynamic disease process that results when the PH dropresults in net mineral loss over time. It is one of the most prevalent diseases affecting mankind. Cariogenicbacteria enter the dental biofilm early in life and subsequently invade the host tissue during favourableenvironment condition, to cause the disease. Many studies and researches show that this disease processcan be interrupted. This article will give a clear idea of the method by which the host defence system can bearoused to combat dental caries caused by the crucial antigen related to Streptococcus mutans. Analyzingthe fact that more effective public dental health care measures are needed to combat this dental caries, thisarticle critically evaluates the recent signs of progress in the development of mucosal adjuvants, deliverysystems for the dental vaccine, and also limitations of caries immunization.

Highlights • Pneumomediastinum is a relatively uncommon consequence of COVID-19 • Pneumomediastinum with COVID-19 can be seen without positive pressure ventilation • Conservative management is still the treatment of choice, COVID-19 is a relatively new and rapidly emerging disease. Given current knowledge of the disease process, it is of the utmost importance to gain further insight into its different clinical manifestations. In this report we describe three cases involving Hispanic males with COVID-19 all of whom developed pneumomediastinum during their hospital course. We want to emphasize the importance of this adverse event despite their non-smoking history and the exclusion of positive pressure ventilation. Frequent chest radiographs help with early recognition of this disease process. Early detection of pneumomediastinum is important as this could lead to worse morbidity if left unrecognized despite its usually benign nature.

This study aims at emphasizing the role of MRS in management of post therapeutic response of different stages of the disease of multiple sclerosisBackground : Multiple Sclerosis is a chronic inflammatory, and degenerative autoimmune disorder of the CNS that is characterized by unpredictable clinical relapses and remissions and by progression of disability over time. MRS has the ability to characterize the chemical pathology of brain, as well as regions of the brain that are not associated with structural abnormalities on conventional MRI. So it can help to define the natural history of the disease process and it can help in monitoring metabolic responses to therapy Patients and Methods : A study, included 40 patients who presented with clinically diagnosed multiple sclerosis followed by conventional MRI and referred for further assessment by MR spectroscopy study .Results : The age of included patients ranged from 18 to 45 years with a mean age of 34.67±8.23 years. 60% of the patients were females and 40% of them were males, the sensitivity, specificity and positive predictive value of H-MRS in the diagnosis of MS were 94.4%, 76.2%, 71.5% respectively compared to 87.3%, 69.2%, and 65.8% in case of c-MRI.Conclusion Adding MR spectroscopy to conventional MRI increases the specificity and accuracy of MRI study in diagnosis and follow up of therapeutic response of Multiple sclerosis

Alzheimer's disease (AD) is an age-dependent, incurable mental illness that is associated with the accumulation of aggregates of amyloid-beta (Aβ) and hyperphosphorylated tau fragments (p-tau). Detailed studies on postmortem AD brains, cell lines, and mouse models of AD have shown that numerous cellular alterations, including mitochondrial deficits, synaptic disruption and glial/astrocytic activation, are involved in the disease process. Mitophagy is a cellular process by which damaged/weakened mitochondria are selectively eliminated from the cell. In AD, impairments in mitophagy trigger the gradual accumulation of defective mitochondria. This review will focus on the recent progress in understanding the molecular mechanisms and pathological role of mitophagy and its implications for AD pathogenesis. We will also discuss the novel concept of the regulation of mitophagy as a therapeutic avenue for the prevention and treatment of AD.

While current armamentarium of medications play a substantial role in Crohn’s disease (CD) remission and maintenance, a still significant number of patients will require operative intervention when their disease is refractory to medical treatment, progress while on medications, develop complications or become end stage fistulizing and/or stricturing disease. CD is mainly an intestinal disease. However, recent interest in the bowel mesentery in general, and especially in the extra-intestinal mesenteric manifestations that is tightly coupled with intestinal pathological features drew the attention to a potential role of the mesentery in CD. It has been proposed that the bowel mesentery has its own substantive anatomic entity, as well as physiologic distinctiveness that it is no longer regarded as bystander tissue in human body. Being highly involved and active in local and systemic inflammatory response increased its recognition of centrality in homeostasis in disease process.

As with any other disease, the severity of glaucoma varies and the disease progression happens at a variable pace. Understanding the importance of the severity of a finding in terms its significance for the particular person under consideration should be clear, but is often not considered. This chapter stresses the importance of assessing this issue of severity, and, additionally, shares a method of how that can be done. This method not only applies to every type of glaucoma, but also for any disease process.

Abdominal aortic aneurysms (AAAs) occur predominately in men. Accordingly, much of the literature describing this major disease process comes from studies and observation of male patients. However, while women are less likely to develop AAA, those women who do are known to have comparatively worse outcomes than their male counterparts. While such differences have prompted consideration of different management strategies between the sexes, no such formal recommendations have yet been proposed in society guidelines. This chapter reviews existing literature on the population of women with AAA and explores key differences in epidemiological trends, risk factors, pathogenesis, disease progression, screening initiatives, and clinical presentation between men and women regarding AAA disease.

Background and purpose The study aimed to obtain optometric findings of amyotrophic lateral sclerosis (ALS) patients in different stages of the disease, and to determine the relation between ocular data and ALS-related features; that is, functional and cognitive impairment and staging. Methods The optometric protocol included tests of the ocular motility [broad-H test and Northeastern State University College of Optometry (NSUCO) test], near point of convergence (NPC), error refraction, best-corrected visual acuity, and binocular visual alignment, and an ocular symptoms questionnaire. The functional measures included the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-r) and Milano-Torino staging (MiToS), and cognitive impairment was assessed using the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Demographic and clinical features were also collected, including whether the patients used an eye-tracking communication device (ETCD). Results Two-hundred consecutive ALS patients (median age of 64 years, 118 males and 82 females) in different stages of disease were recruited. Nearly 70% of patients reported at least one ocular symptom, and the use of an ETCD was found to be significantly related to the presence of most symptoms. Moreover, the severely symptomatic group was characterized by significantly lower ALSFRS-r total and subscale scores, and higher MiToS. Abnormal NPC values were significantly related to lower ALSFRS-r total and bulbar-subscale scores. Patients with acceptable NSUCO test values exhibited significantly higher ECAS scores. Conclusions The presence of ocular alteration in patients in different stages of ALS supports the idea that this is a multisystem disorder and emphasizes the importance of optometric evaluations in multidisciplinary assessments to address ocular impairment early in the disease process.