Intellectual Decline Research Articles

Identification of biallelic intronic EPM2A mutations in a Lafora disease kindred.

Lafora disease (LD) is a severe autosomal recessive disease, which usually presents as seizure and myoclonus, followed by behavioral changes, dysarthria, intellectual decline, and finally progressed to dementia and a vegetative state. The main cause of LD is the loss-of-function mutations in EPM2A and NHLRC1 that encode laforin and malin, respectively. Targeted genetic testing is the gold standard to confirm the diagnosis of LD. To describe the pathogenic role of biallelic EPM2A intronic mutations carried by patients in a family diagnosed as LD. Here, we present clinical findings in a patient presenting with epileptic seizures and Lafora bodies in muscle biopsy. Long-read DNA and RNA sequencing were performed to identify the causative mutation. Western blot and qPCR confirmed the pathogenic role of biallelic EPM2A intronic mutations. Genetic testing identified two intronic mutations in EPM2A which caused aberrant mRNA splicing. c.301+1 G > A in EPM2A caused aberrant splicing at donor site and resulted in intron retention in transcript NM_005670.4, while c.476+14860 C > A caused aberrant splicing in transcript NM_001368129.2 and NM_001368132.1. Our findings expand the spectrum of variants in LD disease, additionally providing evidence linking non-coding regulatory regions mutations to LD disease.

All roads lead to (New) Rome: Byzantine astronomy and geography in a rapidly changing world

During the first few centuries CE, the centre of the known world gradually shifted from Alexandria to Constantinople. Combined with a societal shift from pagan beliefs to Christian doctrines, Antiquity gave way to the Byzantine era. While Western Europe entered an extended period of intellectual decline, Constantinople developed into a rich cultural crossroads between East and West. Yet, Byzantine scholarship in astronomy and geography continued to rely heavily on their ancient Greek heritage, and particularly on Ptolemy’s Geography. Unfortunately, Ptolemy’s choices for his geographic coordinate system resulted in inherent and significant distortions of and inaccuracies in maps centred on the Byzantine Empire. This comprehensive review of Byzantine geographic achievements—supported by a review of astronomical developments pertaining to position determination on Earth—aims to demonstrate why and how, when Constantinople fell to the Turks in 1453 and the Ottoman Empire commenced, Byzantine astronomers had become the central axis in an extensive network of Christians, Muslims and Jews. Their influence remained significant well into the Ottoman era, particularly in the context of geographical applications.

From Legislator to Experts: The Decline of Intellectuals in Ravelstein

Anti-intellectualism is rooted in American historical tradition and has gradually become the most prominent social trend in American society. The rise of anti-intellectualism is also the process of changing the role of intellectuals. With the popularity of anti-intellectualism, authority possessed by intellectuals gradually weakened, not only authority over knowledge but also authority in power mechanism, which ultimately led to intellectuals constantly seeking role transformation. From the aspect of anti-intellectualism and role transformation of intellectuals, extreme egalitarianism inherent in anti-intellectualism and populist politics has expelled intellectuals from being legislators. After being legislators, intellectuals transformed into interpreters, but the interpreter was impacted by division among intellectuals and conflict between intellectuals and the public caused by anti-intellectualism. As anti-intellectualism intensified, intellectuals’ chosen role as experts was unable to cope with the overall anti-intellectual atmosphere of society. Based on Saul Bellow’s Ravelstein as a model, this paper will discuss how anti-intellectualism has affected the transformation of the role of intellectuals regarding social phenomena as well as the characters depicted in the novel.

Muḥammad Hilāl Effendi: An Arab Intellectual and Bureaucrat in the Late Ottoman Period

Muḥammad Hilāl Effendi (1840–?) was an important Ottoman bureaucrat and intellectual. However, despite his prominence, comparatively little is known about his life and works. Muḥammad Hilāl was a graduate from al-Azhar University, which enabled him to serve as a judge in both in Sharia and the then-newly established Tanzimat courts in various provinces of the Ottoman Empire. During his professional tenure, he authored three memoranda addressed to Sultan Abdülhamid II, as well as several religious treatises in Arabic. Significantly, Muḥammad Hilāl does not appear in standard Arabic biographical compilations of his era. Instead, he is mentioned only as the father of Sāṭi‘ al-Ḥuṣrī, who was one of the most prominent theorists of Arab nationalism. However, Hilāl’s memoranda are discussed in the Turkish secondary literature and there, inexplicably, the fact that he was the father of Sāṭi‘ al-Ḥuṣrī has gone largely unnoticed. One, therefore, could claim that Muḥammad Hilāl became a victim of the nationalist fragmentation of post-Ottoman historiography. This paper proposes to serve as a starting point for a re-evaluation of Muḥammad Hilāl Effendi's identity, career, and writings. In doing so, it sheds light on the intellectual climate of the Ottoman Empire in the second half of the 19th century, challenging commonly held notions of intellectual stagnation and decline in this period.

Analysis of 9 patients with adolescence-onset methylenetetrahydrofolate reductase deficiency

Objective: To explore the diagnosis and treatment of adolescence-onset methylenetetrahydrofolate reductase (MTHFR) deficiency. Methods: This was a retrospective case study. Nine patients with adolescence-onset MTHFR deficiency were diagnosed at Peking University First Hospital from January 2016 to December 2022, and followed up for more than 1 year. Their general information, clinical manifestations, laboratory tests, cranial images, MTHFR gene variants, diagnosis, treatment, and outcome were analyzed retrospectively. Results: The 9 patients came from 8 families. They had symptoms at age of 8.0 years to 17.0 years and diagnosed at 9.0 years to 17.5 years. Eight were male and 1 was female. Two patients were brothers, the elder brother developed abnormal gait at 17.0 years; and the younger brother was then diagnosed at 15.0 years of age and treated at the asymptomatic stage, who was 18.0 years old with normal condition during this study. The main manifestations of the 8 symptomatic patients included progressive dyskinesia and spastic paralysis of the lower limbs, with or without intellectual decline, cognitive impairment and behavioral abnormalities. Totally, 15 variants of MTHFR gene were identified in the 9 patients, including 8 novel variants. Five patients had brain image abnormalities. Increased plasma total homocysteine level (65-221 μmol/L) was found in all patients, and decreased to 20-70 μmol/L after treatment with betaine and calcium folinate. Besides, the 8 symptomatic patients had their behavior and cognitive problems significantly improved, with a legacy of lower limb motor disorders. Conclusions: Late-onset MTHFR deficiency can occur in adolescence. The diagnosis is usually delayed because of non-specific clinical symptoms. The test of blood total homocysteine could be used as a selective screening test. Eight novel varients of MTHFR gene were identified. Timely treatment can improve clinical condition significantly, and pre-symptomatic treatment may prevent brain damage.

Fungsi Intelektual Lanjut Usia di Panti Werdha

Background of Study:The elderly period is described as a period of decline, where many changes occur, including a decrease in physical, psychosocial cognitive and intellectual functions. Impact on the decline in daily social activities in the elderly. The purpose of this study was to determine the intellectual function of the elderly at Griya Asih Lawang Werdha Home, Malang Regency. Methods: This research design is descriptive. The population used was 30 people with total sampling. The variable in this study is the intellectual function of the elderly measured using the SPMSQ questionnaire. Data analysis using percentages then presented in the form of frequency distribution tables. This research was conducted on February 27, 2023 to March 3, 2023 at Panti Wedha Griya Asih Lawang Malang Regency. Results: The results showed that most of the respondents as many as 21 people (70%) experienced damage to intellectual function. Conclusion: most respondents had decreased intellectual function, added age, education and social life affect intellectual function decline. It is recommended that ways to maintain and control the decline in intellectual function by implementing healthy living behaviors and conducting brain stimulation Keywords: Elderly, Intellectual Function, Nursing Home

Multitarget Protective Effects of JUB on Aβ-Induced Neurotoxicity and the Mechanism Predication Using Network Pharmacology Analysis.

Amyloid-β (Aβ) is one of the core factors in the pathogenesis of Alzheimer's disease (AD), and the accumulation of its aggregates in the brain can form age-related plaques, leading to brain cell damage and intellectual decline, which may be the common intersection of all causes of neurotoxicity. Jujuboside B (JUB) has many characteristics such as hypnosis, sedation, antianxiety, and antioxidant stress. However, it is still unclear whether JuB can alleviate the neurotoxicity caused by Aβ. Our study demonstrates that JUB improves learning and memory deficits in the nematode model. At the same time, JUB increases the antioxidant activity, prevents excessive accumulation of lipid synthesis, and resists endogenous lipofuscin deposition, thereby inhibiting the toxic effect of Aβ. In vitro, JUB can improve Aβ1-42-induced neuronal apoptosis level through the Bax/Bcl-2/caspase-3 signaling pathway and restore mitochondrial function in SH-SY5Y cells. The network pharmacology has been used to predict the potential neuroprotective mechanism of JUB. In summary, JUB exhibits neuroprotective properties employing both a neural cell and a nematode, which provides a basis for screening candidate ingredients for preventing AD.

P142: Dementia diagnosis: the potential onset of suicidal risk

Objective:Being diagnosed with dementia can be a hectic and critical period. While severe dementia may act as a shield when it comes to suicidal risk, mild and early dementia stages may still preserve cognitive functions to elaborate a suicidal plan. Having insight may lead to feelings of despair and sadness that patients find unbearable to deal with. The aim of this article is to review the current literature regarding suicidal risk after a dementia diagnosis.Methods:Review of the most recent literature regarding the risk of suicide among patients with a recent dementia diagnosis. The research was carried out through the PubMed and UptoDate databases, using the terms “dementia”, “diagnosis” and “suicidal risk”.Results:Previous research showed inconclusive findings, with some authors suggesting a higher risk of an early suicide attempt in patients recently diagnosed with dementia, and others suggesting otherwise. Nowadays, the literature mainly reports that older adults with recent dementia diagnoses are at increased risk of endeavoring suicide. There is an important requirement to offer appropriate support to patients and their families, at the time, or as soon as possible, when a dementia diagnosis is made, to diminish the risk of suicide attempts in these patients.Conclusion:Patients with recent diagnosis of dementia, or diagnosed at an earlier age, seem to have higher suicidal risk. The period immediately after diagnosis is when individuals need greater support, so these results demand for better assistance for those experiencing such intellectual decline.

Implementasi Kebijakan Penanggulangan Stunting di Puskesmas Pangkalan Balai Kabupaten Banyuasin

The problem of stunting in Indonesia is a serious threat that requires proper handling. Toddlers who are stunted have a risk of intellectual decline, productivity and an increased risk of degenerative diseases in the future. One of the policies made by the Palembang City Government related to tackling stunting incidents, namely through Banyuasin Regent Regulation Number 49 of 2018 concerning accelerating stunting prevention, controlling and reducing integrated stunting. The purpose of this study was to analyze government policies related to stunting prevention in the city of Palembang. The results of the study are that the implementation of the stunting reduction policy has been carried out properly in accordance with Banyuasin Regent Regulation Number 49 of 2018 and the Rembuk Stunting Program by the Banyuasin District Health Office in collaboration with all Banyuasin District Health Centers in order to Accelerate Stunting Reduction in Banyuasin District, the clarity of the stunting prevention policy at the Pangkalan Balai Health Center has been socialized to health workers, the staff in supporting the stunting prevention program at the Pangkalan Balai Health Center is sufficient, the facilities available to run the stunting prevention program at the Pangkalan Balai Health Center is appropriate and appropriate, coordination for the formation of Pangkalan Balai Health Center commitments through cross-sectors, SOPs for the implementation of the stunting policy are available. The results of this study are expected to be an illustration for the puskesmas to be able to further improve stunting services.

A case of cerebrotendinous xanthomatosis with massive xanthomas but without a considerable increase in serum cholestanol levels

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder caused by mutations in the sterol 27-hydroxylase gene (CYP27A1). Due to the deficiency of 27-hydroxylase, the synthesis of bile acids from cholesterol is impaired and excessive cholestanol accumulates in various tissues, such as the central nervous system, tendons, and lenses. Patients with CTX typically manifest intellectual decline, pyramidal tract symptoms, cerebellar symptoms, tendon xanthomas, juvenile cataracts, neonatal jaundice, chronic diarrhea, osteoporosis, and premature cardiovascular disease. Here, we report the atypical case of a 35-year-old female with CTX having massive xanthomas but without a considerable increase in serum cholestanol levels (3.9 µg/mL). In the differential diagnosis of xanthoma, CTX should not be ruled out even if the serum levels of cholestanol are not high, and genetic testing is necessary to make the appropriate diagnosis.

Network pharmacology and mechanism studies of the protective effect of ginseng against Alzheimer's disease based on Aβ pathogenesis.

Alzheimer's disease (AD) is a critical neurodegenerative disease that manifests as progressive intellectual decline and is pathologically characterized by a progressive loss of neurons in the brain. Despite extensive research on this topic, the pathogenesis of AD is not fully understood, while the beta-amyloid (Aβ) hypothesis remains the dominant one and only a few symptomatic drugs are approved for the treatment of AD. Ginseng has been widely reported as an effective herbal medicine for the treatment of neurodegenerative diseases such as dementia. Therefore, we explored the protective effects of ginseng in AD by a network pharmacological approach based on the pathogenesis of Aβ. 21 major ginsenosides were screened based on ultraperformance liquid chromatography-mass spectrometry/mass spectrometry (HPLC-MS/MS) data. Among them, MAPK8, MAPK9, BACE1, FLT1, CDK2 and CCR5 were the core targets. By molecular docking and validation with the in vitro cell model APPswe-SH-SY5Y, we found that ginsenosides Rg3 and Ro have good neuroprotective effects and can reduce the expression of Aβ1-42 in APPswe-SH-SY5Y. Finally, through RT-qPCR experiment, we found that ginsenoside Rg3 targeted MAPK8, FLT1, and CCR5, while ginsenoside Ro targeted MAPK8, MAPK9, FLT1, and CCR5 for its potential anti-AD efficacy.

OTHR-06. NARRATIVE MEDICINE AND THE PRACTICE OF PEDIATRIC NEURO-ONCOLOGY: GRAPPLING WITH THE UNTHINKABLE

Abstract As pediatric neuro-oncology team members work with patients, they engage in life and death struggles on behalf of children. Among patients who survive, many are left with intellectual decline, psychological difficulties, inability to take on daily life skills, and an overall decrease in health-related quality of life (Castellino et al., 2014). Absorbing the weight of these stories of illness and complex survival leads to risk of burnout and moral distress. This research sought to understand how pediatric neuro-oncology team members at a U.S. hospital interact with, interpret, and make meaning of the illnesses, complex recoveries, and deaths of patients as a result of participating in a series of narrative medicine workshops. In the workshops, team members encountered fictional stories of loss and longing for restoration as they engaged in close reading and discussion of a text. Writing about the text after participating in discussion helped members connect more deeply to their own formative stories. Further, it enlarged their capacity to connect to the stories of fellow team members and the narratives of patients and their families. Those who practice narrative medicine seek “to recognize, absorb, interpret, and be moved to action by the stories of others” (Charon et al., 2017, p. 1). Its methods harness creativity and insight to equip those in healthcare not only to diagnose and treat their patients but to bear witness to what patients undergo (Charon et al., 2017). If team members train themselves to see the beauty, pain, complexity, and ambiguity in a work of art, they may in turn see their patients and one another as works of art. The act of engaging in narrative medicine practice as a healthcare team in and of itself alleviates distress and fosters collaborative relationships among team members as they grapple with unthinkable loss in their work.

Shangri-La and the Imperial Imagination in James Hilton’s Lost Horizon

ABSTRACT Since the publication of James Hilton’s Lost Horizon (1933), Shangri-La has become a household term, applied to any peaceful idyll or retreat from the modern world. In the academic community, there is a growing consensus that Shangri-La is a purely unreal, imaginary place in the novel of a utopian genre. Nevertheless, how Shangri-La emerged and exists remains a mystery. Therefore, this essay explores how Hilton’s Shangri-La came into being in two forms: an imagined paradise in the East with exotic chinoiserie, and the cultural Other to the West, which is governed by imperialism in the western imagination in the wake of global expansion and colonization. The literary strategies employed by James Hilton in Lost Horizon make Shangri-La an incarnation that epitomizes the imperial ambitions following the demise of the British Empire, with its concomitant economic, intellectual and cultural decline.

Intelligence … moving beyond the lowest common denominator.

Despite a century of use in assessing children for predicting academic success, IQ theory and assessments largely overlook the intellectual repertoires of adolescents and adults that are not common, including declarative, procedural, and tacit knowledge. Such knowledge and skill repertoires are essential elements of adult intellectual life and livelihood. A proposal for considering a wider range of knowledge and skills in the definition and assessment of intelligence is offered, along with ideas for moving forward in both research and applications. When intelligence is considered beyond the lowest common denominator, it is clear that there are many important questions have yet to be answered about adolescent and adult intellectual development, maintenance, and decline, occupational performance, relations between intelligence and nonability traits, and the role of engagement in day-to-day intellectual functioning. The proposed focus is to reconsider what it means to be an intelligent adult beyond the IQ measures and to recognize that adults, on average, are far more "intelligent" than they have been considered to be by traditional IQ assessments developed over the last century. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

THE EFFECTIVENESS OF AUTISM CHARACTER STIMULATION ROOM AT AUTISM SERVICE CENTRE BATAM THROUGH BEHAVIORAL ARCHITECTURE

Autism or commonly referred to as autism spectrum disorder often occurs in children at an early age. Not only that, the symptoms of autism result in the failure of the brain's nervous system and sensory bodies as well as the intellectual decline in individuals who experience it. Sensory malfunctions in the body eventually form 2 characters with different responses to stimuli in a certain environment, namely, hyposensitivity and hypersensitivity. 1 in 500 children in Indonesia is known to have this disorder, so it becomes an issue that is not only developing in the country but has an effect on the world. With a significant increase in the number of autism cases, the need for space will increase. Architects as a profession involved in design play an important role in creating a conducive space for children with autism. However, the space must be adjusted based on the characteristics of autism, so that it can function well for them. This research was conducted by evaluating spaces that have different levels of stimulation in the Batam City Autism Service Center, then developing them. This study also uses a behavioral architectural approach by reviewing the characteristics of people with autism, so that the room can provide comfort for them. The research method used is a qualitative-descriptive form and analyzes the room based on existing criteria. The results of the research are a multifunctional low-stimulus room and a high-stimulus room that can adapt based on variations in activity.

Western Enlightenment and its Impact on Weakening Belief


 
 
 
 Western enlightenment is one of the most important terms of a Western character that has been introduced to Islamic societies in one way or another, or as a result of Muslims being influenced by Western civilization. It is a reason for weakening the belief of the members of the Muslim community and by all media means and advanced scientific technique as well.
 The purpose behind this is to challenge and question the Islamic constants and to seek to distract Muslims from building their future and drowning them in the problems of identity and thought, and that the goal of all of this is to destroy the true Islamic religion from the hands of its members, What is published today is of ideological suspicions, sectarian strife and ideas of atheism.
 Contemporary Jahiliyyah has claimed at the beginning of the Renaissance that it could turn its back on religion and then continue to practice life in a normal manner without any deficiency or imbalance, claiming that when it gets rid of religion, it would remedy what was in its life of deficiency and imbalance! And slough off that religion that disturbs the peace of life, disrupts its impulse, spreads ignorance, blocks thought, and blocks light from humanity.
 By experience it has been proven that there is no real source of values and principles other than religion. They said that it is the mind and they said that it is the nature, and they said the human soul, and they said science, and they said philosophy.
 
 
 
 
 By departing from religion and common sense, they reached anxiety, madness, loss, confusion, mental illness, nervousness, suicide, alcohol, drugs, crime, decadence and metamorphosis that distort the nature... and moral, intellectual and spiritual decline in all fields of political, economic and social life at the level of individuals, groups and peoples. Given the importance of the matter, it was one of the reasons and reasons for research and the current study. Therefore, this research came tagged: (The Western Enlightenment and its Effect on Weakening the Creed). This study was divided into an introduction and a conclusion, and two sections.

The Phenomenon of Nonbelief and Methods to Confront It

Abstract Atheism is not a new problem, rather its existence starts from the beginnings of humanity, and it covers each and every thought related to denying the existence of the Creator of this universe, Glory be to Him, whether it was with the forerunners of secularism or with those who came after them from the Communists and Marxists. And dealing with it superficially, the Western terms falling under secularism, modernity and freedom are terms that serve external parties whose goal is to strike religious beliefs. The prevention of suspicions by rooting the sense of faith in the Muslim community through absolute faith in Allah Almighty is the best protection from the danger of atheism and the suspicions that are raised against the religion. The duty of the official authorities in Islamic countries is to make special channels well prepared to repel suspicions and what is raised by the enemies of the religion, to be an explanation for the people for fear of falling into these suspicions. The Holy Qur’an and the Prophet’s Sunnah are the fortified shield for every believer Muslim if he reflects on the Qur’an and the purified Sunnah. The relationship of religion with science is a strong one; it is not like what is ranged by the enemies of religion. Rather, the Holy Qur’an urges learning, reflection and induction. Calling to Allah or going to an intellectual, doctrinal and moral decline, Allah forbid.

Islamic instruments and their effectiveness in satisfying the needs of Iraqi society - selected applications -

Banks provide their customers with a variety of services, either to finance their projects, or to satisfy their needs. Islamic banks are distinguished from commercial banks in their choice of financial services and transactions that satisfy those needs, and provide capital for projects in accordance with Islamic law. Among these transactions are: (Islamic instruments) that can be applied in Iraqi society to meet the need for transportation, housing and academic study.going to an intellectual, doctrinal and moral decline, Allah forbid.

Afterword: Reassessing Arabic in South Asia

In his learned and stimulating article that helps frame the contributions to this roundtable while also outlining directions for future work in this area, Nile Green notes the striking fact that it has been nearly a hundred years since the last substantial English survey of the field was attempted. That was M. G. Zubaid Ahmad's “Contribution of India to Arabic Literature,” completed as a PhD dissertation under the supervision of the noted Orientalist Sir Thomas Arnold (d. 1930) at the School of Oriental Studies (as it was then known), University of London, in 1929. It was subsequently published with a preface by another distinguished Orientalist, Sir Hamilton Gibb (d. 1971), and retains some scholarly interest to this day.1 That interest lies not only in the descriptions of the many Arabic-language works it lists—going well beyond Carl Brockelmann's classic Geschichte der arabischen Litteratur in this respect—but also, in hindsight, in the assumptions that guide Ahmad's work. Ahmad believed there was little in the Arabic literature surveyed that showed any originality, partly because there was not much remaining to be said in fields like Qur'anic exegesis, the reported teachings of the Prophet Muhammad (hadith), or law by the time Indian scholars began engaging seriously with these subjects. It was also partly to do with an intellectual decline well underway by the time relevant areas of inquiry had reached India. The intellectual landscape remained unrelieved whether one looked at religious or secular literature, or even at writings in Persian for that matter: “… in spite of the abundance of Persian literature produced in India, nothing original is found in these contributions.”2

The Causes of Stagnation in Islamic Civilization, in the Context of the Intellectual Decline in Muslim Societies

The Causes of Stagnation in Islamic Civilization, in the Context of the Intellectual Decline in Muslim Societies