Complex Group Of Disorders Research Articles

Unmasking the Face of a Rare Disease – Progressive Nodular Histiocytosis

Abstract Non-Langerhans cell histiocytoses (NLCHs) are a complex group of disorders which can be difficult to diagnose due to their confounding clinical and microscopic features. Progressive nodular histiocytosis (PNH) is a rare subtype of NLCH characterized by benign, xanthogranulomatous lesions on the skin and mucous membranes. Clinical features of PNH involve the gradual emergence of multiple yellow-brown papules and nodules, with histological examination demonstrating the presence of foamy tissue macrophages, spindle-shaped cells within a fibrocollagenous matrix, and Touton cells. We present a rare case of a 55-year-old female patient with progressively increasing facial nodules, where clinical, histopathological, and immunohistochemical findings clinched the diagnosis of PNH.

Screening of eating disorders and its related factors among Syrian undergraduates: a cross-sectional study

BackgroundEating disorders (EDs) are a complex group of disorders that affect mental and physical health and pose a challenge for medical professionals to diagnose. This study aims to screen for eating disorders among Syrian university undergraduates.Methods and materialsA cross-sectional study was conducted among Syrian university students using a self-administered questionnaire. The questionnaire consisted of three sections: socio-demographic characteristics, dietary habits and barriers to healthy eating, and the Sick, Control, One, Fat, Food (SCOFF) score. The chi-square test was used to evaluate the factors related to eating disorders.ResultsOf 728 students, 45.3% were males and 54.7% females. The majority of participants studied medicine 32.3%, followed by pharmacy 25.7% and dentistry 17.6%. Overweight and obese participants represented 21.4% and 6.8% respectively. Merely 36% of students reported adopting a healthy diet, a greater percentage of females 58.8% reported having snacks compared to males 48.5% (P = 0.006), a higher percentage of females 38.8% reported consuming fast food compared to males 26.6% (P < 0.001). Most of the students' eating habits worsened during exams 55.7%, females 60.6% markedly reported worse eating habits during exams compared to males 50% (P = 0.017).Lack of time 72.7%, not accessible 38.3%, and unenjoyable 31.6% were frequent barriers to healthy food. About 20.3% of students screened positive for probable eating disorders. Factors that elevate the likelihood of acquiring an ED encompass being female, having a lower or higher BMI, eating worse during exams, and psychological behaviors.ConclusionsProbable EDs were prevalent among Syrian undergraduates. The addressed socio-demographic and psychological factors were significantly affecting students’ eating behaviors. These findings can be used to provide targeted lifestyle modification advice via health promotion programs for these specific groups.

Neurogenomics contribution to neurodegenerative Diseases

Introduction: Neurodegenerative diseases are a group of complex disorders that progressively impair the structure and function of the nervous system, resulting in debilitating symptoms and reduced quality of life for affected individuals. Over the past few decades, advances in the field of genomics have revolutionized our understanding of the underlying molecular mechanisms driving these disorders. Neurogenomics, the intersection of neuroscience and genomics, has emerged as a crucial discipline in unraveling the genetic and molecular underpinnings of neurodegenerative diseases. Neurogenomics focuses on deciphering the genetic variations that contribute to the susceptibility and progression of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and Huntington's disease. Advances in DNA sequencing technologies have enabled researchers to identify specific genetic mutations and variations that are associated with increased disease risk. By studying the genetic mutations involved in neurodegenerative diseases, neurogenomics has provided valuable insights into the underlying disease mechanisms. These insights have led to a deeper understanding of protein aggregation, mitochondrial dysfunction, inflammation, and other cellular processes implicated in disease progression. By harnessing the power of neurogenomics through further studies, researchers and clinicians are moving closer to the goal of effectively preventing, diagnosing, and treating neurodegenerative diseases, thus offering hope to millions of individuals affected by these challenging conditions. Conclusion: Neurogenomics has emerged as a pivotal field in unraveling the complex interplay between genetics and neurobiology in neurodegenerative diseases. By dissecting the genetic architecture, elucidating molecular mechanisms, and paving the way for targeted therapies, neurogenomics offers new avenues for understanding, diagnosing, and ultimately treating these disorders.

Phthalimides Represent a Promising Scaffold for Multi‐Targeted Anticancer Agents

AbstractFrom the last two decades, phthalimide analogues received prime interest from scientists due to its potent inhibitory action on different cancer‐causing receptors. A variety of anticancer drugs are coming into the market but challenges of drug resistance, toxicities, and failure in therapy still remain. Cancer is a group of complex disorders it involves multiple receptors. So there is a need of targeting multiple receptors to get desired potent anticancer drugs with minimum harmful effects. Phthalimide scaffolds fit into these criteria as it is extensively reported for the inhibition of different cancer receptors such as VEGFR, HDAC, EGFR, TNF‐α, etc. The multi‐targeted mechanism of phthalimide derivatives plays a major role in anticancer therapy. Due to this advantage, there is the hope of developing some novel effective multi‐targeted anticancer agents. Consider structural features and pharmacological advancement of phthalimide analogues may fulfill the current need of cancer patients. In this review, we covered history, chemistry, SAR, anticancer mechanisms, and the current status of phthalimide derivatives reported till 2022. The article specifically focused on different cancer‐causing receptors inhibited by phthalimide derivatives and their mechanism of action in brief. Finally, we provided the future scope and role of phthalimide derivatives in multi‐targeted anticancer drug discovery.

Updates on the Diagnosis and Treatment of Peripheral Autonomic Neuropathies.

Autonomic neuropathies are a complex group of disorders and result in diverse clinical manifestations that affect the cardiovascular, gastrointestinal, urogenital, and sudomotor systems. We focus this review on the diagnosis and treatment of peripheral autonomic neuropathies. We summarize the diagnostic tools and current treatment options that will help the clinician care for individuals with peripheral autonomic neuropathies. Autonomic neuropathies occur often in conjunction with somatic neuropathies but they can also occur in isolation. The autonomic reflex screen is a validated tool to assess sympathetic postganglionic sudomotor, cardiovascular sympathetic noradrenergic, and cardiac parasympathetic (i.e., cardiovagal) function. Initial laboratory evaluation for autonomic neuropathies includes fasting glucose or oral glucose tolerance test, thyroid function tests, kidney function tests, vitamin-B12, serum, and urine protein electrophoresis with immunofixation. Other laboratory tests should be guided by the clinical context. Reduced intraepidermal nerve density on skin biopsy is a finding, not a diagnosis. Skin biopsy can be helpful in selected individuals for the diagnosis of disorders affecting small nerve fibers; however, we strongly discourage the use of skin biopsy without clinical-physiological correlation. Ambulatory blood pressure monitoring may lead to early identification of patients with cardiovascular autonomic neuropathy in the primary care setting. Disease-modifying therapies should be used when available in combination with nonpharmacological management and symptomatic pharmacologic therapies. Autonomic function testing can guide the therapeutic decisions and document improvement with treatment. A systematic approach guided by the autonomic history and standardized autonomic function testing may help clinicians when identifying and/or counseling patients with autonomic neuropathies. Treatment should be individualized and disease-modifying therapies should be used when available.

Whole Genome Sequencing, Focused Assays and Functional Studies Increasing Understanding in Cryptic Inherited Retinal Dystrophies.

The inherited retinal dystrophies (IRDs) are a clinically and genetically complex group of disorders primarily affecting the rod and cone photoreceptors or other retinal neuronal layers, with emerging therapies heralding the need for accurate molecular diagnosis. Targeted capture and panel-based strategies examining the partial or full exome deliver molecular diagnoses in many IRD families tested. However, approximately one in three families remain unsolved and unable to obtain personalised recurrence risk or access to new clinical trials or therapy. In this study, we investigated whole genome sequencing (WGS), focused assays and functional studies to assist with unsolved IRD cases and facilitate integration of these approaches to a broad molecular diagnostic clinical service. The WGS approach identified variants not covered or underinvestigated by targeted capture panel-based clinical testing strategies in six families. This included structural variants, with notable benefit of the WGS approach in repetitive regions demonstrated by a family with a hybrid gene and hemizygous missense variant involving the opsin genes, OPN1LW and OPN1MW. There was also benefit in investigation of the repetitive GC-rich ORF15 region of RPGR. Further molecular investigations were facilitated by focused assays in these regions. Deep intronic variants were identified in IQCB1 and ABCA4, with functional RNA based studies of the IQCB1 variant revealing activation of a cryptic splice acceptor site. While targeted capture panel-based methods are successful in achieving an efficient molecular diagnosis in a proportion of cases, this study highlights the additional benefit and clinical value that may be derived from WGS, focused assays and functional genomics in the highly heterogeneous IRDs.

Multiple developmental craniovertebral junction anomalies associated with fusion of the third and fourth cervical vertebrae: A case report and review of the literature

Craniovertebral junction (CVJ) is formed by the occipital condyles of the skull, atlas (C1), and axis (C2). CVJ anomalies are a complex group of disorders with a variable course and complicated line of management. A cross-sectional imaging is indispensable for the evaluation of CVJ as it may unmask pathologies unsuspected by clinical evaluation and conventional radiography. We present a case report in which we describe multiple developmental CVJ anomalies in a 25-year-old male patient. These include fusion defects of anterior and posterior arches of C1, os odontoideum, atlantoaxial subluxation (with compression of the cervical cord at the cervicomedullary junction), and fusion of C3 and C4 vertebral bodies as well as posterior elements.

Mitochondrial Myopathy, Encephalopathy, Lactic acidosis and Stroke-Like Episodes Syndrome Presenting With Anton-Babinski Syndrome and Concurrent Occipital Lobe Seizures

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a complex group of disorders with multisystem involvement that have a wide range of biochemical and genetic defects. The earliest symptoms of MELAS typically include easy fatigability, muscle weakness, encephalopathy with stroke-like episodes, recurrent headaches and seizures. The pathogenesis of stroke-like episodes manifesting as focal deficits like acute cortical blindness is not fully understood. We present an eight-year-old, right-handed boy with MELAS confirmed by the presence of pathogenic missense variant mutation (mt.3243A>G) presenting with acute intermittent reversible episodes of cortical blindness and Anton-Babinski Syndrome secondary to concurrent occipital lobe seizures captured during video electroencephalography (V-EEG) monitoring, in addition to the neuro-imaging which was not consistent with acute ischemic stroke.This case highlights the importance of the V-EEG monitoring besides clinical testing and radiographic correlation during acute cortical blindness episodes in MELAS as occipital lobe seizures could be a part of the symptomatology.

Cerebral Palsy and Epilepsy in Children: Clinical Perspectives on a Common Comorbidity.

Cerebral palsy (CP) is a frequent cause of childhood disability often associated with a complex group of disorders, including epilepsy, which is reported to impact approximately 40% of affected individuals. This retrospective study involved a group of children affected by CP, some of whom also had comorbid epilepsy. The aim of this study was to report our experience of analyzing, in particular, (a) some of the clinical aspects of the different type of CP, and (b) the relationship between the clinical data of children affected by CP plus epilepsy and each type of CP. Methods: This retrospective single-center study was performed with 93 children admitted to the Pediatric Department of the University of Catania, Italy, affected by CP and distinguished according to the type of motor clinical presentation, with 46 showing epileptic seizures, compared to a control group of 136 children affected by epilepsy without other neurologic disorders. Results: Among the 93 CP children, 25 (27%) had spastic quadriplegia (plus one patient with dystonic quadriplegia), 39 (42%) had spastic hemiplegia, 11 (12%) had spastic diplegia (plus two with ataxia and one with dyskinetic CP), and 14 (15%) did not have a well-defined type of CP. The frequency of epilepsy was higher in affected CP children who showed major motor dysfunction (GMFCS IV–V types). As regards the 46 children with CP plus epilepsy, compared to the group of the control, the age of epilepsy onset was found to be statistically significant: 21 ± 35.1 months vs. 67 ± 39.7. Conclusions: Epilepsy represents one of the most frequent comorbidities of cerebral palsy. In children with CP, particular attention should be paid to the early identification and treatment of comorbid epilepsy.

Successful pregnancy outcome in a multiparous lady with medical myriad-mixed connective tissue disorder, tuberculosis, chronic hypertension and recurrent pregnancy loss

Autoimmune diseases/mixed connective tissue disorders are chronic and complex group of disorders with multi-systemic involvement. Untreated cases have significant morbidity and poor quality of life. There is a T helper cell paradigm from T helper1 to T helper 2 in pregnancy and autoimmune diseases may flare or improve in pregnancy depending on the type of autoimmune disease and pre-conception disease activity. There is enough evidence to support that individuals affected with autoimmune diseases are susceptible to tuberculosis (TB) infection and conversely auto-antibodies like antinuclear antibody, and rheumatoid factor are detected in sera of patients with active tuberculosis. If this association applies in pregnancy and if immunosuppressive state of pregnancy would further augment this association is not reported. We report a rare case of a 40 year old multigravida with mixed connective tissue disorder (MCTD) with features of systemic lupus erythematosus, deforming rheumatoid arthritis with gangrenous changes and auto-amputation of toes. She had reactivation of TB in the index pregnancy. She was also a chronic hypertensive, hypothyroid and had recurrent pregnancy losses. Index pregnancy was following invitro fertilisation (IVF) conception with donor oocyte and was managed by a multidisciplinary team in obstetric high dependency unit and delivered a healthy baby; both mother and baby were discharged in stable condition. We report this case as there are no reports of MCTD with active TB in pregnancy and to review if pregnancy affects the course of MCTD, TB or association between these two, and management options in such high risk cases.

Artificial intelligence and deep learning in glaucoma: Current state and future prospects.

Over the past few years, there has been an unprecedented and tremendous excitement for artificial intelligence (AI) research in the field of Ophthalmology; this has naturally been translated to glaucoma-a progressive optic neuropathy characterized by retinal ganglion cell axon loss and associated visual field defects. In this review, we aim to discuss how AI may have a unique opportunity to tackle the many challenges faced in the glaucoma clinic. This is because glaucoma remains poorly understood with difficulties in providing early diagnosis and prognosis accurately and in a timely fashion. In the short term, AI could also become a game changer by paving the way for the first cost-effective glaucoma screening campaigns. While there are undeniable technical and clinical challenges ahead, and more so than for other ophthalmic disorders whereby AI is already booming, we strongly believe that glaucoma specialists should embrace AI as a companion to their practice. Finally, this review will also remind ourselves that glaucoma is a complex group of disorders with a multitude of physiological manifestations that cannot yet be observed clinically. AI in glaucoma is here to stay, but it will not be the only tool to solve glaucoma.

Myopathic Blepharoptoses: A New Classification System.

Myopathic blepharoptoses (ptoses) is a complex group of disorders. To date, no formal categorization scheme has been developed based on associated ocular and systemic findings, genetic fingerprint, treatment, and prognosis for each ptosis in this group. We report a new classification scheme for myopathic ptoses. Literature review and classification development. A new classification scheme of myopathic ptoses includes isolated static myopathic ptosis (congenital ptosis), static myopathic ptosis associated with aberrant innervation and those associated with periocular abnormalities, and progressive myopathic ptoses that affect the levator muscle and other muscle groups in childhood and adulthood. Making the distinction of myopathic ptosis type early will maximize patient outcomes by optimizing surgical and systemic management and facilitating the recruitment of subspecialists to care for patients with these challenging conditions.The authors present a comprehensive and effective myopathic ptosis classification scheme to optimize surgical management and facilitate subspecialty care.

Analysis and Design of Rehabilitation Device in Sensory Integration Therapy for Autism Children

A group of complex disorders in terms of brain development is known as Autism Spectrum Disorder (ASD). The rehabilitation device playing vital roles in this institute which provide crucial assistance in the process of helping the autism people. Nowadays, the development of the technologies has led to the integration of the rehabilitation device with technology to sophisticating the function of the device. In this study, the integration of the electrical and the electronic technologies will be implemented for the purpose of attracting the learning desire of the autism children. The performance of autism children in the aspect of ‘attention’ will be identified and discussed. Overall data that had been collected showed an improvement in the performance of both of the autism children. Hence, autism children showed that they had improved their performance by paying attention on the task that had been given and less doing unnecessary things that can keep their attention away.

STUDY OF CASES OF ARM IN RURAL POPULATION

introduction&#x0D; Anorectal malformations (ARMs) comprise a spectrum of birth defects in newborn male and female children which include rectum, anal canal, genitalia and urinary tract. ARMs incidence ranging 1:2000-5000 live birth.1,2The spectrum of ARM varies from mild anterior displacement of anus to complex anomalies such as cloacal exstrophy.[4] The main goal of management is correct diagnosis and surgery so as to achieve good anatomic and functional outcome so that a child can lead his or her life as normal as possible.&#x0D; MATERIAL AND METHODS&#x0D; All children of pediatric age group from 0 to 15 years admitted in surgical wards and/or pediatric wad of Index Medical College, Hospital and Research Centre, Indore with diagnosis of Anorectal Malformations who will undergo all stage of treatment and follow-up. This was prospective and observational study.&#x0D; DISCUSSION&#x0D; The management of infants with ARM continues to be a challenge to pediatric surgeons, worldwide. For better results, precise anatomical reconstruction and careful preservation of Structure is required. ARM being a complex group of disorders, is not easy to diagnose at primary healthcare level. The social awareness about the disease is low and it also varies with Sex of child, place of living and education of parents.&#x0D; CONCLUSION Anorectal malformation is a surgically treatable entity. Early restorative surgery leads to good outcome. Time being the essence, awareness about the condition, hospital delivery and detailed neonatal examination is advisable. In developing countries like India, where illiteracy and poverty are prevalent and where there is neglect of female child, early diagnosis and referral to specialty centres for surgery is always commendable in terms of social acceptance and a sound psyche.

Metabolomics Analysis of Skeletal Muscles from FKRP-Deficient Mice Indicates Improvement After Gene Replacement Therapy

Muscular dystrophy-dystroglycanopathies comprise a heterogeneous and complex group of disorders caused by loss-of-function mutations in a multitude of genes that disrupt the glycobiology of α-dystroglycan, thereby affecting its ability to function as a receptor for extracellular matrix proteins. Of the various genes involved, FKRP codes for a protein that plays a critical role in the maturation of a novel glycan found only on α-dystroglycan. Yet despite knowing the genetic cause of FKRP-related dystroglycanopathies, the molecular pathogenesis of disease and metabolic response to therapeutic intervention has not been fully elucidated. To address these challenges, we utilized mass spectrometry-based metabolomics to generate comprehensive metabolite profiles of skeletal muscle across diseased, treated, and normal states. Notably, FKRP-deficient mice elicit diverse metabolic abnormalities in biomarkers of extracellular matrix remodeling and/or aging, pentoses/pentitols, glycolytic intermediates, and lipid metabolism. More importantly, the restoration of FKRP protein activity following AAV-mediated gene therapy induced a substantial correction of these metabolic impairments. While interconnections of the affected molecular mechanisms remain unclear, our datasets support the notion that global metabolic profiling can be valuable for determining the involvement of previously unsuspected regulatory or pathological pathways as well as identifying potential targets for drug discovery and diagnostics.

Towards a therapy for mitochondrial disease: an update.

Preclinical work aimed at developing new therapies for mitochondrial diseases has recently given new hopes and opened unexpected perspectives for the patients affected by these pathologies. In contrast, only minor progresses have been achieved so far in the translation into the clinics. Many challenges are still ahead, including the need for a better characterization of the pharmacological effects of the different approaches and the design of appropriate clinical trials with robust outcome measures for this extremely heterogeneous, rare, and complex group of disorders. In this review, we will discuss the most important achievements and the major challenges in this very dynamic research field.

Revisiting transthyretin related cardiac amyloidosis: Case report and review of literature.

Amyloidosis is a complex group of disorders that can involve many organs and cause their dysfunction. Cardiac involvement indicates worse prognosis and influences treatment strategies. Cardiac amyloidosis is an under-diagnosed entity and high index of clinical suspicion and careful interpretation of basic diagnostic tools such as electrocardiogram and echocardiography is needed for early detection. Congestive heart failure due to restrictive pattern and/or conduction system abnormality, in absence of coronary artery disease should raise suspicion. We present a case of transthyretin related cardiac amyloidosis and discuss the key clinical and diagnostic findings along with review of existing literature regarding its management and outcomes.

Pediatric forms of vasculitis

Primary vasculitides that affect children are a challenging and complex group of disorders that may involve any system of the body and lead to significant morbidity and mortality. In recent years, there have been significant advances in the field of childhood vasculitides, including the development of classification criteria and outcome assessment. Although some forms of vasculitis occur in both children and adults, considerable differences exist between childhood and adult vasculitides; we review childhood vasculitides, thus highlighting their differences with the adult forms of the disease. We will also discuss monogenic forms of vasculitis, such as deficiency of adenosine deaminase type 2 (DADA2) and haploinsufficiency of A20 (HA20).

Sevoflurane anaesthesia for nasal surgery in a patient with multiple chemical sensitivity

Multiple chemical sensitivity syndrome is a group of complex disorders that include psychiatric disorders, chronic fatigue and/or respiratory problems. This syndrome could be triggered by specific allergens and toxins that cause neurophysiological sensitization and appearance of clinical symptomatology. Anaesthesia for these patients always poses a challenge for anaesthetist, because they need to find and use drugs that do not trigger or aggravate symptoms of disease. Therefore, sevoflurane in these circumstances might be the ideal anaesthetic. Performing general anaesthesia with sevoflurane as sole anaesthetic agent, together with a series of environmental measures formed basis for successful anaesthesia and surgery in our patient with a multiple chemical sensitivity syndrome.

Eosinophilic Enteritis: A Delayed Diagnosis

Eosinophilic Gastrointestinal Disorders (EGID) are a rare and complex group of disorders that are characterized by eosinophilic infiltration of the gastrointestinal tract. Eosinophilic esophagitis (EoE) is limited to the esophagus while eosinophilic gastroenteritis (EGE) can involve any portion of the GI tract. Patients often present with a wide range of signs and symptoms including abdominal pain, nausea, vomiting, dysphagia, diarrhea, and even more serious manifestations such as intestinal obstruction or perforation as any length or layer of the GI tract can be involved such as mucosal, muscular, or serosal1,4,10. As a part of the work-up, patients frequently undergo CT scans and multiple endoscopies before the diagnosis is finally made as was true in our case of a 59 year-old male patient presenting with 2 months of nausea, abdominal pain and weight loss. He underwent EGDs, colonoscopies, a video capsule study and balloon enteroscopy before the diagnosis was confirmed histologically. Endoscopic findings can be variable and often include mucosal erythema, edema, strictures, polypoid lesions and ulcerations8. Radiographic findings are also unpredictable and may include mural thickening, nodularity, luminal narrowing, and perienteric inflammation suggestive of an acute inflammatory condition2,3,8. The diagnosis is confirmed on histopathological examination of biopsies that must show >15-50 eosinophils/high power field based on the location in the GI tract. In our patient, erythema, scalloping, whitish exudate, and patches of villous blunting with a flat pink appearance were noted in the duodenum to proximal ileum endoscopically with >50 eosinophils/hfu confirming the diagnosis of eosinophilic enteritis. This class of diseases is often found in patients with a history of allergic disorders including asthma, eczema, seasonal allergies and food allergies suggestive of hypersensitivity in the etiology of the disease although our patient had no such known history4. Elimination diets and steroids are the mainstay of therapy and often lead to complete resolution of symptoms as well as endoscopic and radiographic findings in up to 90% of patients as was seen in our patient, although some patients have a chronic remitting course8.Figure: Endoscopy showing erythematous gastric nodules in the antrum of the stomach.Figure: Endoscopy showing erythema, scalloping, and villous blunting throughout portions of gastrointestinal tract.