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Type 2 diabetes mellitus (T2DM) is a chronic progressive disorder and is associated with significant morbidity and mortality. The concept of T2DM remission and the reversal of diabetic parameters to normal levels has been gaining momentum over the past years. T2DM remission is increasingly being recognized by various global guidelines. Multiple models have been developed and validated for quantifying the extent of remission achieved. Based on favorable clinical evidence, T2DM remission can be considered as the therapeutic goal in diabetes management and, in select cases, as an alternative to expensive treatment options, which can be burdensome as T2DM progresses. This narrative review discusses the available strategies, such as lifestyle interventions, physical activity, bariatric surgery, medical nutrition therapy, and non-insulin glucose-lowering medications, for achieving T2DM remission. Although the concept of T2DM remission has emerged as a real-world option, effective implementation in routine clinical practice may not be feasible until long-term studies prove the efficacy of different approaches in this regard.

Otosclerosis, a hereditary disorder characterized by disordered resorption and deposition of bone, results in progressive hearing loss. Osteogenesis imperfecta (OI) is a genetic disorder characterized by recurrent fractures, blue sclera, and varying degrees of hearing impairment; and is a known risk factor for otosclerosis. After adolescence, the risk of fracture decreases, reducing the need for follow-up in OI. However, otosclerosis is a progressive disorder. In this report, we discuss two cases of familial otosclerosis with different clinical features. We hypothesize that the difference in hearing level correlates with the difference in computed tomography findings. The mother, whose case was considered severe, was prescribed hearing aids, while the daughter, who had normal hearing level, was regularly followed up.

Dementia is a diverse category of chronic and progressive disorder, which is commonly associated with a loss of memory, difficulty in judgment, impaired language, cognitive impairment, and various other symptoms that affect a person’s daily routine life and social life. Dementia affects about 50 million people around the globe. Dementia exists in varied forms and is associated with various neurodegenerative disorders. Alzheimer's disease is the most common form, which accords for about 60% of thecases. Abnormal agglomeration of proteins in the brain has been linked to the pathogenesis of dementia. Autophagy is a necessary protein clearance mechanism, which is dependent on lysosomes. It is a basic physiological process that performs the crucial function of maintaining protein homeostasis within the cells. The autophagic dysfunction in dementia further complicates the disease by hampering the degradation and removing abnormal pathogenic proteins. In order to understand autophagic dysfunction, it is essential to know the genetics of autophagy as well as the mutations This understanding at the genetic level helps definethe relationship between dementia and autophagic dysfunction for developing the potential remedies for the treatment of dementia.

Gaucher disease (GD) is the most common lysosomal storage disorder, resulting from a deficiency in the activity of a lysosomal enzyme glucocerebrosidase, which is involved in the catabolism of sphingolipids. The phenomenal progress in understanding the pathogenesis and development of specific therapy of this disease over the past 60 years dramatically changed the clinical phenotype of GD, turning a severe progressive disorder into an asymptomatic metabolic defect. The evolution of the understanding of GD associated with fundamental discoveries in the field of cell biology, biochemistry and genetics may be of interest to a wide audience as a model of the effective work of the scientific community in the treatment of rare metabolic pathology.Болезнь Гоше (БГ) наиболее распространенное и хорошо изученное заболевание из группы лизосомных болезней накопления, возникающее вследствие наследственного дефицита активности лизосомного фермента кислой -глюкозидазы (глюкоцереброзидазы), участвующего в катаболизме сфинголипидов. Без преувеличения феноменальные успехи в изучении патогенеза и разработке специфической терапии данного заболевания во 2-й половине XX начале XXI в. кардинально изменили клинический фенотип БГ, превратив тяжелое прогрессирующее заболевание в бессимптомный метаболический дефект. Эволюция представлений о БГ, тесно связанная с фундаментальными открытиями в области клеточной биологии, биохимии и генетики, может представлять интерес не только для узкой группы специалистов, занимающихся диагностикой и лечением БГ, но и для более широкой аудитории как модель эффективной работы научного сообщества в лечении редкой метаболической патологии.

Background: Peyronie’s disease (PD) is a progressive disorder of the connective tissue of the tunica albuginea of the penis that produces an abnormal curvature, painful erections and different degrees of erectile dysfunction (ED). The aim of this study is to evaluate our initial experience in the surgical treatment of PD using an autologous graft of testicular vaginal tunica. Materials and methods: A retrospective study of 23 patients was carried out between 2015 and 2019. The successful surgical stretching rate was defined as a functional 20 degrees of curvature or less. Postoperative sexual function and complications rate were evaluated as secondary objectives. We used the abbreviated IIEF-5 questionnaire and evaluated the sexual function before and after the surgical procedure. Wilcoxon signed-rank test for paired samples (U test) was used, considering a value of pResults: Only one patient presented a recurrence of the penile curvature, resulting in a 95.6% success rate of functional stretching. We observed a 1.6 and 0.9 difference between pre- and postoperative total score and satisfaction ( p = 0.002 and p = 0.003 respectively) Conclusion: In this series, the use of testicular vaginal tunic was found to be safe and effective with a significant change in the quality of sexual life, especially reflected in the overall satisfaction after the procedure and a low rate of complications. Level of evidence: Not applicable for this multicentre audit.

Pulmonary arterial hypertension (PAH) is a rare, progressive disorder associated with a poor prognosis if not treated appropriately. Fortunately, new treatment options have significantly improved survival rates and prognosis. Despite these advances, many patients do not receive the diagnosis until years into their disease or are inappropriately diagnosed. Early referral to specialized treatment centers that allows for early diagnosis and initiation of treatment significantly improves patient outcomes including survival as well as reduction in hospital admissions, which are a main driver of economic burden of disease. It is important that evidence-based guidelines are followed and treatment is individualized based on patient-specific factors. Pharmacologic therapies carry a very high cost for PAH; however, extensive utilization of management strategies may hinder access to medication and may lead to disease progression. Cost containment strategies may help to facilitate care coordination for earlier diagnosis and initiation of treatment, adherence to PAH medications, and patient education to ensure they are using medications appropriately to optimize therapy. Managed care pharmacists can play a crucial role in the multidisciplinary team in terms of medication safety, adherence, patient education, and follow-up to improve patient engagement that leads to improved outcomes.

Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease. This progressive disorder is mostly known by its signature symptoms of bradykinesia and rest tremor. The progression of PD is divided into five stages by the Hoehn and Yahr (H&Y) rating scale. The diagnosis of PD and its progress is of utmost importance in providing an effective treatment plan and to manage the disease and maintain quality of life. The goal of this study is to introduce several new higher-order features and use them with a combination of existing lower and higher-order statistical features of EEG signals to diagnose the stages of PD. In this paper, we use the total of 30 higher-order and six lower-order (first and second-order) statistical features extracted from EEG signals of 20 PD patients, along with 20 age-matched healthy control subjects, recorded during rest state, to perform the classification. We use a range of classification methods, and although other methods may have higher overall accuracy, we see that due to our unbalanced dataset, RUS Boosted trees ensemble has the highest sensitivity for this application (highest performance for the late PD class). It is also shown that the accuracy of the classification is improved significantly by using the newly developed features.

Background: Primary synovial chondromatosis (PSC) is a progressive disorder of unknown etiology resulting in formation of multiple loose bodies. If left untreated, it may lead to degenerative changes or malignant transformation to chondrosarcoma. Methods: Seventeen patients who underwent combined posterior and anterior ankle arthroscopy within the same operative session and had histologically confirmed PSC were included in this retrospective study. American Orthopaedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot score was used to evaluate ankle function preoperatively and at a final follow-up. A 3-question survey was used to evaluate patient’s satisfaction at the final follow-up. Results: In 14 patients, loose bodies were found in both compartments of the ankle, in 2 only in the anterior compartment, and in 1 only in the posterior compartment. All patients had evident signs of synovial inflammation in both compartments. The AOFAS Ankle-Hindfoot score increased from the preoperative median score of 65 (range, 29-90) to 95 (range, 65-100) at the final follow-up. Fourteen patients reported they were extremely satisfied with the outcome, 1 was moderately satisfied, and 2 were dissatisfied. No cases of recurrence of synovitis or loose body formation were noted, nor any signs of malignant transformation during the follow-up period. Conclusion: We believe the risk of recurrence of PSC, which is in close relation to malignant transformation, can be minimized by performing a complete synovectomy of the ankle. Our experience and review of literature makes us believe that ankle PSC should be regarded as a whole joint disorder. Performing a combined posterior and anterior arthroscopic procedure within the same operative session should always be considered in patients with ankle PSC. Level of Evidence: Level IV, retrospective case series.

Parkinson being an progressive disorder has drew many challenges in physical therapy management, and having wide variety of signs and symptoms it has always proven as challenging to the therapists, however in last five years there was extremely good progress in management of Parkinson disease. But due to its heterogeneity signs from individual to individual, hardly literature has been proven useful for practice. In multidisciplinary team approach exercise therapy has drastically proven to support and maintain quality of life in daily activities. This review provides the importance of exercise therapy in Parkinson in multi disciplinary approach. Keywords: Excercise therapy, Parkinson, Multidisciplinary.

Tumoral calcinosis is a benign, progressive disorder characterized by massive periarticular deposition of calcium salts into subcutaneous and deeper tissue layers. While a majority of cases present secondary to underlying metabolic disorders, it can rarely present as a primary, idiopathic phenomenon. We present an atypical case of a pediatric patient with a large, ulcerated pedal soft tissue mass found to be consistent with primary tumoral calcinosis. This was confirmed by histopathologic analysis and comprehensive metabolic workup. The patient underwent surgical excision of the mass, with complete resolution of symptoms and no recurrence after a 1-year follow-up period.

Alzheimer's disease is one amongst the progressive disorder that cruelly affects the brain cells. It causes the death of nerve cells and tissue loss in brain. It usually tends to start slowly and aggravates overtime. The symptoms of Alzheimer's disease vary from person to person depending on the severity of the unhealthiness. It exhibits behavioral symptoms such as communication impairments, memory loss, taking a longer time to complete usual activities, and change in attitude and behavior. If the problem worsens over time, then it cannot be cured. Hence it should be identified at the earlier stage itself and treat the patient to lead a normal life on their own. Deep learning algorithms exhibit marvelous performance over conventional machine learning algorithms in identifying the complex patterns in the large volumes of high-dimensional medical imaging data. Hence, recently significant attention has been paid to apply deep learning for medical diagnosis. In this research, Deep Convolution Neural Network (DCNN) and VGG-16 inspired CNN (VCNN) models have been built to classify the different stages of Alzheimer's Disease from the Magnetic Resonance Imaging(MRI) images. Experiments are carried out on an ADNI dataset and the results obtained show that the proposed models achieved excellent accuracy.

Inclusion body myositis is a rare sporadic inflammatory-degenerative myopathy of the elderly. Despite being the commonest type of acquired myopathy after the age of 50, misdiagnosis is extremely common. The most frequent hurdle in identifying new cases is the wrong diagnosis of polymyositis or motor neuron disease. Novel insights into pathogenic mechanisms have heralded the quest for newer therapeutics as well as drug repurposing in this otherwise progressive disorder.

Peripheral artery disease of the lower limbs is a chronically progressive disorder characterised by the presence of occlusive lesions in the medium and large arteries that result in symptoms secondary to insufficient blood flow to the lower extremities. It is both a manifestation of systemic atherosclerosis and a marker of increased cardiovascular morbidity and mortality. Because of its highly heterogenous clinical picture, a detailed history and physical assessment, a high degree of suspicion for peripheral artery disease and the use of the ankle–brachial pressure index is essential to identify patients with peripheral artery disease. This will allow early administration of basic pharmacotherapy and lifestyle changes to reduce cardiovascular events, minimise claudication symptoms and enable optimal revascularisation to prevent loss of limb function.

Cardiac amyloidosis is a progressive disorder and is sometimes difficult to diagnose even when suspected in the appropriate clinical setting. We present an interesting case of rapidly progressive light-chain cardiac amyloidosis and highlights the importance of close monitoring even when the initial biopsy and imaging findings are not pathognomonic for amyloidosis. (Level of Difficulty: Beginner.), Graphical abstract, Cardiac amyloidosis is a progressive disorder and is sometimes difficult to diagnose even when suspected in the appropriate clinical setting. This…

Introduction: Dementia is a progressive disorder associated with age, which is characterized by deterioration of individuals’ cognitive functions such as the ability to perform routine tasks. With the increase of human life expectancy, the prevalence of dementia patients will reach 152 million in 2050. Unfortunately, there is no treatment available to cure dementia or alter the course of its progression. However, there is an area of support for patients and caregivers to assist daily living. Technological devices and applications are increasingly advancing, exploiting sensory data for dementia patients and homecare using smartphones to permit monitoring of their activities. Aim: This paper uses the labeled dataset besides comparing the 3-classification algorithm to evaluate whether or not the algorithms deployed can classify the activities with high accuracy. Results: A public data is used to classify human activities into one of the six activities, BigML platform is used to build machine learning models. Results show that machine learning algorithms can achieve high accuracy. The activity recognition algorithms are highly accurate using ridged regression and deep neural networks, with almost all activities being recognized correctly over 98% of the time. Conclusion: An application of smartphones can be utilized for human activities monitoring by proposing a high level for dementia patients and homecare monitoring services. Using this service, the patients only need to carry the smartphone, and their caregivers simply need to use the application that monitors their patients’ activities.

Background: Lymphedema is a progressive disorder characterized by impairment of lymph flow from tissues to the blood circulation due to damage of lymphatics. Treatment can be surgical or nonsurgical. A great number of operative procedures described in the literature demonstrate no single method exists that could be regarded as a standard. Nonsurgical therapy consists of a set of four physiotherapeutic measures, if properly performed; it treats the cause of lymphedema in a manner free of side effects, this set is called complex physical therapy (CPT). Criteria and facilities of CPT are not available in Iraq now. Materials and Methods and Results: Below is a short clinical experience of seven cases (nine diseased lower limbs) presented at our clinic for management of lymphedema who were all managed successfully during the decongestive period using adjustable Velcro wraps (AVW). Conclusions: In the absence of ideal CPT facilities, AVW can be used as a single therapeutic modality for treatment of lymphedema.

Introduction Bipolar disorder (BD) has been reconceptualised as a progressive disorder that develops from mild to severe presentations. An empirical staging model – the Empirically Developed Clinical Staging Model for BD (EmDe-5) – was developed in a previous study. This study aims to further validate that model using a larger and more representative Spanish sample. Material and methods 183 BD outpatients were recruited at 11 sites in Spain. Assessment included clinical characteristics of the BD (number of hospitalisations, number of suicide attempts, comorbid personality disorders), physical health (BMI, metabolic syndrome, number of physical illnesses), cognition (SCIP), functioning (permanently disabled due to BD, FAST), and quality of life (SF-36). The CGI-S, VAS-S, and psychopharmacological treatment pattern were used as external validators. Results Ten patients (51.5%) were classified as stage 1, 33 (18%) as stage 2, 93 (50 8%) as stage 3, 37 (20 2%) as stage 4, and 10 (5 5%) as stage 5. All profilers, other than number of suicide attempts (p = 0.311) and comorbid personality disorder (p = 0.061), exhibited worse scores from stage 1 to 5. As expected, VAS-S and CGI-S scores were worse in the later stages. Regarding treatment, early stages (1–2) were associated with the use of one to three drugs while late stages (4–5) were associated with four or more drugs (p = 0.002). Conclusions We confirm the EmDe-5 staging model's construct validity. The ease of obtaining the profilers, together with the operational criteria provided to quantify them, will facilitate the use of the EmDe-5 staging model in daily clinical practice.

This scientific commentary refers to ‘Progression and regression of nerve fibre pathology and dysfunction early in diabetes over 5 years’ by Ziegler et al. (doi:10.1093/brain/awab330).

BackgroundAcute injury following brain trauma may evolve into a chronic and progressive disorder. Chronic consequences of TBI have been understudied, in part, due to the lack of robust behavioral changes that are delayed in onset as well as chronic and progressive. Assessment of the chronic consequences of TBI also must distinguish behavioral changes that arises due to age vs those that develop and evolve over time due to injury.MethodsC57BL/6 mice receive single closed head injury (CHI) and are analyzed at 7DPI, 14DPI or 180DPI on neurological severity score, open field, rotarod, beam walk, and simple-complex wheel.ResultsIn the center of open field, injured mice have a turn bias at 180 days post-injury (DPI) not present at 7DPI. On rotarod, injured mice have shorter latencies at 7DPI, but not at 180DPI due to a large age effect in sham-injured mice. On beam walk at 180DPI, both sham and injured groups more slowly traverse a 2cm and 1cm beam than at 7DPI. Foot-faults show no significant effects of age or injury. On simple wheel injury affects speed at 14DPI with no effect on distance travelled. The lack of injury-dependent effects on beam walk or simple-complex wheel despite visible impairment was the impetus to assess limb position using Deeplabcut™ markerless tracking. Custom Python scripts were then developed to compute beam walk absition or foot fault severity (integral of limb displacement over time), and step frequency and quadrupedal limb coordination in simple-complex wheel. On the 2cm beam, age increased absition in all limbs of uninjured mice and both forelimbs of injured mice. On the 1cm beam both forelimbs and the left hindlimb of injured mice at 180DPI have larger absition than uninjured mice at 180DPI or injured mice at 7DPI. On a simple wheel injury affected speed only at 14 DPI with no effect on distance travelled. In contrast, injured mice at 180DPI developed a compensatory running strategy by increasing step frequency variability. This allowed injured mice at 180 DPI to reach sham-level quadrupedal limb coordination and improve running speed as compared to 14 DPI assessment. On complex wheel, injured mice at 180DPI do not express this compensatory running strategy resulting in impaired quadrupedal limb coordination. These data suggest chronic and progressive motor deficits of injured mice at 180DPI.ConclusionsA single impact produces chronic and progressive motor deficits. Quantitative motor analysis using DeepLabCut™ tracking reveals deficits not seen using standard outcomes.

Alzheimer's disease (AD) as common late-life dementia is pathologically associated with the irreversible and progressive disorder, misfolding, deposition, and accumulation of the brain proteins. Especially, the formation of fibrous amyloid plaques by aggregation of amyloid-β peptides is the pathological cause of this neurologic disorder disease. Besides, tau protein isoforms destabilize the microtubule filaments through post-translational modifications and induce nerve cells' death. Amyloid-β peptides and tau proteins are considered as the critical symptom and reliable molecular biomarkers for the early diagnosis of AD. AD is characterized by impaired thinking proficiencies, cognitive decline, memory loss, and behavioral disability. Since there is no efficacious therapy for AD at present, the development of precise sensing tools for the early diagnosis of this disease is essential and crucial. Aptamer-based biosensors (aptasensors) have acquired utmost importance in the field of AD healthcare, due to excellent sensitivity and specificity, ease-of-use, cost-effectiveness, portability, and rapid assay time. Here, we highlight the recent developments and novel perspectives in the field of aptasensor design to quantitatively monitor the AD biomarkers. Finally, some results are represented to achieve a promising viewpoint for introducing the novel aptasensor test kits in the future.

Background Alzheimer's disease (AD) is a chronic, progressive disorder that causes declines in cognitive and physical functions. This condition places severe burdens on families and caregivers. Delaying progressive declines in cognitive function and reducing their burden are thus important. Relationships between early treatment response and subsequent outcomes of schizophrenia and major depressive disorder have been reported. We thus aimed to investigate the relationships between treatment response to antidementia drugs in AD after 6 months (M) and subsequent outcomes. Methods Eligible individuals comprised 194 patients diagnosed with presumed AD. Of these, 110 patients who received antidementia drugs for the first time and were assessed using the Mini-Mental State Examination (MMSE) at 6 M, 12 M, and 24 M were categorized as responders (n = 84) or nonresponders (n = 26). Responders were defined as showing a change in MMSE after 6 M the same as or lower than that in the natural course according to previously reported data. Results No significant differences in baseline characteristics (age, sex, education, or comorbidities) were seen between groups. Mean MMSE score at baseline was significantly lower in responders (18.0) than in nonresponders (20.7; P = 0.008). Mean change from baseline MMSE was significantly smaller in responders than in nonresponders at both 12 M (-0.46 vs -2.5; P = 0.04) and 24 M (-0.78 vs -4.4; P = 0.001). Conclusions Treatment response with antidementia drugs after 6 M predicted better outcomes at 12 M and 24 M. Treatment response should be assessed every 6 M, and treatment should be reconsidered accordingly.

Introduction: Osteoporosis is a worldwide public health problem that affects both male and females. It is a silent progressive disorder that affects the skeletal system and leads to diminished bone density and fracture. Therefore, awareness, attitude, and practices of people about osteoporosis contribute significantly to primary prevention and early detection of disease. Objective: the present study conducted to assess the knowledge of the female medical students at King Faisal University about osteoporosis in Saudi Arabia. Study design: A cross-sectional study conducted at the medical college of King Faisal University at Al-Ahsa region, Saudi Arabia. The study included all female medical students at King Faisal University, through an online self-administered questionnaire using the Osteoporosis Knowledge Assessment Tool (OKAT) questionnaire. Results: The total number of participants was 176 female medical students, with 58.7% response rate. The age of participants ranged between 17 and 27 years, with a mean and standard deviation of 21.46±1.54 years. The participant's knowledge score about osteoporosis was as follow: 65.1% had satisfactory knowledge, 32.2% had poor knowledge, and only 2.3% of the participant had good knowledge. Conclusion: Most of the participants had a satisfactory knowledge score on osteoporosis. However, there was a significant gap in knowledge regarding the risk factors such as high salt intake. The good knowledge score was significantly low in the present study compared to worldwide. Therefore, an educational effort is needed to improve knowledge and the quality and reliability of information about osteoporosis targeted undergraduates and young females in Saudi Arabia.

Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disorder with a poor prognosis. Recently, balloon pulmonary angioplasty (BPA) has been reported to be an effective treatment for inoperable patients with CTEPH. However, this catheter-based treatment has potentially life-threatening vascular complications. To improve the efficacy and safety of BPA, we assessed the morphological evaluation of organised thrombus and the vascular injury by BPA procedure. Methods In this study, we assessed the morphology of organised thrombi and the vascular injury observed by angioscopy during BPA in 28 lesions from nine CTEPH patients. Results Angioscopy visualised various forms of organised thrombi such as ‘Mesh’, ‘Slit’, ‘Flap’ and ‘Mass’ and allowed for a detailed evaluation of organised thrombus that was difficult to do by conventional contrast angiography. In addition, after balloon dilation for BPA, angioscopy revealed a haemorrhage due to a vessel wall injury caused by wiring and/or ballooning. Conclusions Assessment of organised thrombus and vascular injury by angioscopy might contribute to improving the treatment of the patients with CTEPH.

A movement disorder emergency is an acute or sub-acutely evolving neurological illness predominated by a primary movement disorder. Although Parkinson's disease (PD) is a chronic, progressive disorder, patients may present with a variety of acute symptoms. Timely diagnosis and management is crucial to reduce mortality and morbidity. The underlying causes of an emergency in PD may be attributable to either disease related emergencies which occur as a direct consequence of the disease pathophysiology or secondary to anti-parkinsonian medications, such as Parkinsonism-hyperpyrexia syndrome, acute psychosis, etc. Indirect disease related emergencies, are those which not directly associated with the disease but occur secondary to deficits produced by the disease, e.g. falls and pneumonia. Emergencies in patients with PD may also be related to deep brain stimulation or systemic illnesses which are unrelated to PD. Complications may also occur during the surgical management of patients with PD owing to the effects of the disease on cardiovascular and respiratory functions or interactions of PD medication with anesthetic agents. Additionally, although motor complications are expected to form a majority of ER admissions in PD, several studies have reported indirect or non-PD related complications as the predominant primary reason for emergency admissions. The present article aims to review emergencies encountered in patients with PD with focus on the identification and management of these emergencies.

A distrofia muscular de Duchenne (DMD) é uma doença hereditária progressiva, de herança recessiva ligada ao cromossomo X. As manifestações clínicas se iniciam na infância com enfraquecimento muscular progressivo. Objetivo: Foi caracterizar o perfil clínico e funcional apresentado pelos pacientes com DMD, que se encontravam em acompanhamento na Associação Brasileira de Distrofia Muscular (ABDIM). Método: Foram coletados os dados de 58 pacientes com o diagnóstico de DMD. Resultados: Os resultados obtidos caracterizaram os pacientes com DMD da ABDIM, proporcionando dados como: idade da população, complicações clínicas mais freqüentes e nível de independência em relação á funcionalidade, caracterizando a diversidade do perfil clínico e funcional desses pacientes. Conclusão: Concluiu-se que o perfil clínico e funcional dos pacientes da ABDIM apresentou-se heterogêneo, mostrando que a progressão da doença varia de sujeito para sujeito dentro da população estudada, mesmo levando em consideração a faixa etária.

Objectives: Age-related macular degeneration (AMD) is a progressive disorder among people aged ≥50 years. Some dietary factors associated with the susceptibility to AMD include dietary glyc...

Valvular heart disease is a progressive disorder, which often requires surgery, principally when it is severe and/or the patient is symptomatic. Over the last 60 years the incidence of rheumatic heart disease has declined, but the number of valve surgeries performed did not follow such decrease in rheumatic incidence. In fact, important changes in patient characteristics and in the distribution of the type of valvular lesions are emerged. This valvular disease variation also increases operative risk and the length of hospital stay (LOS). Nowadays, multiple factors are associate to LOS, which indicates the sum of pre-operative and post-operative-LOS. In this study, Multiple linear regression (MLR) was used to discover a model that was able to predict LOS knowing characteristic of patients, and the factors that most affect LOS were evaluated.

Parkinson's Disease (PD)is one of the most common non-curable neurological disorders up till now. It is also a progressive neurodegenerative disease. It is a progressive disorder that affects movement and progresses slowly, beginning with a minor tremor in just one hand. In the early stages of Parkinson's disease, the face may have little or no movement, and the arms may not swing while walking. As the disease progresses, voice may become soft or slurred, and symptoms may worsen.

Pulmonary arterial hypertension (PAH) featured a debilitating progressive disorder. Here, we intend to determine diagnosis‐valuable biomarkers for PAH and decode the fundamental mechanisms of the biological function of these markers. Two mRNA microarray profiles (GSE70456 and GSE117261) and two microRNA microarray profiles (GSE55427 and GSE67597) were mined from the Gene Expression Omnibus platform. Then, we identified the differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs), respectively. Besides, we investigated online miRNA prediction tools to screen the target gene of DEMs. In this study, 185 DEGs and three common DEMs were screened as well as 1266 target genes of the three DEMs were identified. Next, 16 overlapping dysregulated genes from 185 DEGs and 1266 target gene were obtained. Meanwhile, we constructed the miRNA gene regulatory network and determined miRNA‐508‐3p‐NR4A3 pair for deeper exploring. Experiment methods verified the functional expression of miR‐508‐3p in PAH and its signalling cascade. We observed that ectopic miR‐508‐3p expression promotes proliferation and migration of pulmonary artery smooth muscle cell (PASMC). Bioinformatic, dual‐luciferase assay showed NR4A3 represents directly targeted gene of miR‐508‐3p. Mechanistically, we demonstrated that down‐regulation of miR‐508‐3p advances PASMC proliferation and migration via inducing NR4A3 to activate MAPK/ERK kinase signalling pathway. Altogether, our research provides a promising diagnosis of predictor and therapeutic avenues for patients in PAH.

Group 1 pulmonary hypertension (or pulmonary arterial hypertension) is a rare, highly complex, and progressive disorder that is incurable and ultimately can lead to premature death. PAH causes significant physical, social, work, and emotional burdens among affected patients and their caregivers. Early diagnosis and initiation of treatment is required for best outcomes; however, the clinical presentation of PAH is nonspecific and frequently overlaps with several other conditions, often leading to a delay in diagnosis or misdiagnosis. In the past decades, increased understanding of the pathobiology of PAH has led to changes in its definition. Additionally, contemporary PAH registries have shown greater survival rates among patients with PAH and have allowed for the development of risk calculator tools that are now used to drive therapeutic goals. To date, multiple PAH-specific therapies have been developed, and all currently target one of 3 pathways that contribute to the endothelial dysfunction pathogenesis of PAH (prostacyclin, endothelin, and nitric oxide pathways). Because PAH is classified into 7 subgroups, it is essential that individuals are grouped appropriately for the efficacy of treatment and avoidance of harm. As health-related quality of life for PAH is multifactorial, it is important that patients are involved in the clinical decision-making process and have access to multidisciplinary care. The purpose of this review is to update healthcare professionals on the management of PAH with the most current information on epidemiology, pathophysiology, clinical presentation, and diagnostic considerations.

Background: Alzheimer’s disease (AD) is known to cause an enormous impairment to the quality of life and impact in the health system; meanwhile, studies show that in the coming years, the number of affected individuals will continue to grow. It is also believed that amnestic mild cognitive impairment (MCI) could represent an early symptomatic form of AD, which precedes dementia. Methods: The present study aimed to evaluate the intracranial pressure (ICP) through a noninvasive method in patients with AD and MCI, seeking for differences when compared to healthy elderlies. This is a cross-sectional, correlational, and observational study of a quantitative character, carried out in a Brazilian city, with patients from the ANEC of the UFSCar. Results: It was found a statistically significant difference between the ICP morphology when analyzing the results in patients with AD and MCI, compared to healthy volunteers. It is known that dementias means a progressive disorder that leads to the loss of independency and function of the patient, although, it is believed that it can be found early ICP alterations in these patients. Nevertheless, considering this is an unprecedent study, it was not possible to compare results with previous studies and literatures. However, the study has a limitation related to the sample size; an expansion of it could possibility lead to different findings. Conclusion: The findings through the ICP measurement could indicate an early diagnosis, which would lead to an early treatment and an improvement in the quality of life of patients with AD. Thus, further investigation and widening studies are encouraged.

Brain is the prime and complex organ of the nervous system in all osseous and boneless organisms. Generally, it is positioned close to the sensory organs in the head. Brain is made up of trillions of networks called synapses that are used to connect and communicate with more than 100 billion cells in the human body. When the brain cells are required to be degenerated, and about to die, then Alzheimer's disease might come into the existence. Alzheimer’s disease (AD) is a progressive disorder that will destroy the brain nerves. This order will profoundly lead to a continuous memory loss, which will adversely affect the mental health and daily routines. Also, Alzheimer’s disease remains as one of the main causes for dementia. So, early and accurate detection and diagnosis of Alzheimer's disease remain as the most significant research area. Normally, doctors will identify and observe the AD from the visualization of the brain magnetic resonance imaging (BMRI) with naked eye. To resolve these challenges, authors have proposed and designed a graphical user interface-based AD screening system that select, detect, and predict Alzheimer’s disease classes by using deep convolutional neural networks (DCNN). For this purpose, brain magnetic resonance imaging (BMRI) has been performed. These MRI images are categorized into four classes: mild demented, moderate demented, very mild demented, and non-demented Alzheimer’s disease. In this paper, deep convolutional neural networks (DCNN) offer a saner solution in numerous disease controls for neurological disorder with a high precision on validation accuracy. GUI-based screening system will identify the healthy or non-demented class accurately so that anyone can easily diagnose the accurate type of Alzheimer's disease.

Amyotrophic lateral sclerosis (ALS) is a progressive disorder which impairs gait and elevates the risk for falls. Current methods of assessing gait in these patients are infrequent and subjective. The goal of this study was to evaluate wearable-based methods for assessing gait to facilitating better monitoring of ambulatory health and ultimately lessen fall risk. Thirty ambulatory patients seen in ALS clinic were guided by a physical therapist on a short walk, during which inertial sensors recorded their movement. Two methods, utilising sensors at the waist or foot, were used independently to estimate gait parameters. Decreased stride length, increased stride duration and decreased walking speed were associated with lower functional walking scores, and the presence of a cane or walker. Overall, there was no group-wide mean walking speed differences between methods, though the waist method overestimated stride length and walking speed in those with more significant gait dysfunction compared to the foot method. Reconstruction of movement using the foot-based sensor resulted in route segments that were 94 ± 1% standard error of the mean (SEM) the length of a centre-to-centre hallway reference vector, with an angular error of 0.66 ± 0.28° SEM.

Alzheimer’s disease (AD) is the most common form of dementia with a growing incidence rate primarily among the elderly. It is a neurodegenerative, progressive disorder leading to significant cognitive loss. Despite numerous pieces of research, no cure for halting the disease has been discovered yet. Phytoestrogens are nonestradiol compounds classified as one of the endocrine-disrupting chemicals (EDCs), meaning that they can potentially disrupt hormonal balance and result in developmental and reproductive abnormalities. Importantly, phytoestrogens are structurally, chemically, and functionally akin to estrogens, which undoubtedly has the potential to be detrimental to the organism. What is intriguing, although classified as EDCs, phytoestrogens seem to have a beneficial influence on Alzheimer’s disease symptoms and neuropathologies. They have been observed to act as antioxidants, improve visual-spatial memory, lower amyloid-beta production, and increase the growth, survival, and plasticity of brain cells. This review article is aimed at contributing to the collective understanding of the role of phytoestrogens in the prevention and treatment of Alzheimer’s disease. Importantly, it underlines the fact that despite being EDCs, phytoestrogens and their use can be beneficial in the prevention of Alzheimer’s disease.

Huntington Disease (HD) is a progressive disorder which often manifests in motor impairment. Motor severity (captured via motor score) is a key component in assessing overall HD severity. However, motor score evaluation involves in-clinic visits with a trained medical professional, which are expensive and not always accessible. Speech analysis provides an attractive avenue for tracking HD severity because speech is easy to collect remotely and provides insight into motor changes. HD speech is typically characterized as having irregular articulation. With this in mind, acoustic features that can capture vocal tract movement and articulatory coordination are particularly promising for characterizing motor symptom progression in HD. In this paper, we present an experiment that uses Vocal Tract Coordination (VTC) features extracted from read speech to estimate a motor score. When using an elastic-net regression model, we find that VTC features significantly outperform other acoustic features across varied-length audio segments, which highlights the effectiveness of these features for both short- and long-form reading tasks. Lastly, we analyze the F-value scores of VTC features to visualize which channels are most related to motor score. This work enables future research efforts to consider VTC features for acoustic analyses which target HD motor symptomatology tracking.

Alzheimer's is a progressive disorder caused by the degeneration of brain cells. It may lead to dementia. Initially, the symptoms will be mild but become more precarious over time. Alzheimer's disease process actually commences unknowingly before 20 years or more, even before the symptoms arise. The symptoms will be notable only after a few years of brain changes such as memory loss, and are realized by the affected person with language problems and difficulty in remembering small things and carrying out daily activities. According to statistics, about 13.8 million people have Alzheimer's disease. There are a few diagnosis techniques for the disease recognized at the later stage but prediction of the disease at the earlier stage is still a challenging task. The disease can even lead to severe problems like dehydration, malnutrition, and death. The objective of this chapter is to give a detailed survey of the various methods and techniques using electroencephalogram signals and psychological parameters of the patients for predicting the disease. An analysis is done on various machine learning techniques and patients are examined with performance metrics such as prediction accuracy and execution time.

Pain is most common symptom associated with progressive disorder, chronic kidney disease (CKD), and is usually undertreated during the early stages of CKD. So, present review was conducted to evaluate the challenges for the management of pain in CKD patients and addresses the scope for considering Diclofenac as suitable alternative for pain management in CKD patient. The database PubMed and Google Scholar were searched from 1970 to Dec 2020 for literature published in English and all studies, review articles that examined the use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in pain management in CKD patients were included. Literatures revealed that there is a considerable challenge in appropriate management of pain in CKD patients include understanding the altered pharmacokinetics and pharmacodynamics of analgesics in CKD patients and the risk of acute interstitial nephritis. The shorter duration of analgesics is acceptable and considered to pose a low risk of acute interstitial nephritis in patients. Considering that Diclofenac has a shorter half-life and high efficacy, it may be well tolerated in patients with CKD. The acceptance of Diclofenac is partly attributed to being a potent COX-2 inhibitor with the lowest IC50 and its rapid onset of action at lowest effective dose. In conclusion, diclofenac may be well tolerated in patients of renal impairment when used at lowest effective dose for shortest dose duration. Diclofenac is worthy of consideration in mild to moderate cases of CKD. For effective pain management, it is vital to evaluate the tolerability and efficacy of the available analgesics critically.

ABSTRACT : Amavata is composed of two words namely- Ama and Vata. The Ama is the product of incomplete digestion which circulates throughout the body and induces heaviness, loss of taste and appetite, body ache, joint swelling and stiffness, constipation etc like symptoms. The Amavata is described under Vata-Kaphaja vikaras since the period of Madhavkara (16th century). It is a chronic inflammatory systemic disorder affecting mainly the synovial joints in the body. It resembles with Rheumatoid Arthritis in the modern pathology. The Amavata is known to be a crippling, chronic and progressive disorder making it difficult to cure. The symptomatic relief is attained by modern medicine but the root cause and pathology of the disease remains untreated. In Ayurveda, the basic treatment principles of Deepana, Langhana, Swedana, Virechana, Basti, Tikta-Katu dravyas are applied for effective management of the root cause of Amavata. A 38 year old female patient with complaints of Shoola, Shotha and Sthamba of the knee, wrist, ankle and metacarpophalangeal joints of both hands was reported in our hospital OPD an year ago. According to the Lakshanas and the blood investigations, the diagnosis was made as Amavata and treatment was planned. Oral medication with Sinhanad Guggul, Vatavidhwans Ras, Arogyavardhini vati, Dashamularistha and Shunti-Eranda kwath along with Valuka sweda was advised. The assessement was made on the basis of subjective and objective parameters. The results did show a significant improvement in the symptoms of the patient and she was able to perform her routine work without any difficulty.

Alzheimer’s disease (AD) is an age-related neurodegenerative and progressive disorder representing the most common form of dementia in older adults [...]

Glaucoma is the global leading cause of irreversible blindness. It is a chronic progressive disorder and, therefore, often requires long-term management with drugs on patients' discretion. However, there is a shortage of antiglaucoma drugs in the current market due to their low bioavailability. This is because there are multiple biological barriers of the human eyes, thereby leading to increased demands for frequent dosage regimen per day of these drugs, which could result in concomitant side effects and eventually reduced patient compliance. Recently, nanomedicines have become optimized alternatives to conventional ophthalmic formulations due to advantages of improved barrier permeability, sustained drug release, tissue targeting, and lowered systemic absorption of instilled medications. These merits provide the active ingredients in these nanomedicines an effective manner to reach the ideal concentrations at sites of damaged nerves, offering a promising platform for neuroprotective treatment of these conditions. In this study, nanomedicines and nanomedicine-based novel strategies for pharmacotherapy of glaucoma were reviewed, including liposomes, niosomes, nanoparticles, and dendrimers. This article intends to offer a comprehensive review of frontier progresses as well as hotspots and issues that appeared in the field of nanomedicines, which may enable a practical flourish in the future. STATEMENT OF SIGNIFICANCE: Recent novel pharmaceutical strategies toward glaucoma, a chronic blinding ocular disease that currently requires frequent daily dosage regimen, based on nanomedicines and nanomaterials have been comprehensively reviewed in this manuscript. The collection of field hotspots and issues in the late years should offer a quick grasp of the general concept and up-to-date threads upon the refinement of existing treatment patterns for glaucoma. Meanwhile, the Conclusion and Future Perspective section given at the end of the text brings out the possible shortages and opinions in terms of ideal research direction, which hopefully could facilitate a future practical flourish in the area.

Chronic obstructive pulmonary disease (COPD) is a common progressive disorder of the respiratory system which is currently the third leading cause of death worldwide. Exhaled breath analysis is a non-invasive method to study lung diseases, and electronic noses have been extensively used in breath research. Studies with electronic noses have proved that the pattern of exhaled volatile organic compounds is different in COPD. More recent investigations have reported that electronic noses could potentially distinguish different endotypes (i.e., neutrophilic vs. eosinophilic) and are able to detect microorganisms in the airways responsible for exacerbations. This article will review the published literature on electronic noses and COPD and help in identifying methodological, physiological, and disease-related factors which could affect the results.

PURPOSE OF REVIEW This article reviews the clinical features, diagnostic approach, and treatments available for amyotrophic lateral sclerosis (ALS) and other motor neuron diseases. The article also provides an update on the genetics and pathophysiology of ALS. RECENT FINDINGS ALS remains a clinical diagnosis without a unique biomarker. The areas of greatest progress include a large expansion in the number of genes associated with familial and sporadic ALS. The discovery of these genes, along with other work, has provided a deeper understanding of the mechanisms of motor neuron failure in ALS. Areas of particular interest include the role of transactive response DNA-binding protein 43 and other RNA-processing proteins in the development of disease. SUMMARY ALS remains a relentlessly progressive disorder with an elusive core pathophysiology. The current mainstay of treatment remains symptom management and palliation, particularly in the setting of a multidisciplinary clinic. The future holds potential for targeted therapies based on an ever-evolving understanding of the pathophysiology of both familial and sporadic ALS.

Parkinson’s disease is a neurodegenerative progressive disorder end with independency for many years at late life, leading to great burden on patient and family life. The available treatment is symptomatic focused on improving life quality of the patient and it’s in need for good communication with the physician. So far there is no easy and practical way for follow up, thus we’ve designed the Parkinson’s disease follow up self-assessment scale aiming to detect ON and OFF time, it’s include PD manifestations, medications and medications adverse effects filled out by the patient family at home in order to mailing it to the physician, and intend to testing it by comparing the performance of patient family with expert staff in using the scale at hospital for 24 hours. Then enquiring about difficulty of using the same scale at home. A 44 PD patient were completed the study. All items accuracy filling out was 93.4% in compare to expert staff. Its mean degree of difficulty was 4/10 and among patients families only 29.54% consider it difficult to use. The ON and OFF time was detected precisely in 92.2% by follow up physician. The proposed scale is precise in detection ON an OFF time and not difficult to use.

The deep learning is strong on not only images (as explained in the previous Chap. 4) but also on sound-type data. It is possible to show that in a serious disease called as Parkinson’s disease (PD). PD is a degenerative disease of the central nervous system. As coming after the Alzheimer’s disease, PD is known among critical common neurodegenerative diseases. The number of people with PD worldwide is quite high and is rapidly increasing, especially in countries (developing) in the context of Asia. The Olmsted County (Mayo Clinic) has reported the life-time risk of Parkinson’s disease at 2% for men. That value is 1.3 for women. It has been confirmed in many sources that the incidence of males is higher. It is stated that the number of PD patients will be doubled by 2030. Early diagnosis of PD disease can also reduce symptoms. Significant symptoms of PD are tremor, stiffness, slow motion, motor symptom asymmetry and impaired posture. In addition, phonation and speech disorders are common in the PD patients. As a result, PD is a chronic and progressive disorder of movements, and symptoms become worse over time. It is reported that almost 1 million people living in the US are an age with Parkinson’s disease.