Miracle-dz/UniFAR-FTUs huggingface dataset:
Modeling of Antigenomic Therapy of Mitochondrial Diseases by Mitochondrially Addressed RNA Targeting a Pathogenic Point Mutation in Mitochondrial DNA*

Background: Point mutations in mitochondrial genome cause severe clinical disorders. Results: We designed recombinant RNA molecules imported into mitochondria of human cells, which are able to decrease the proportion of mitochondrial DNA molecules bearing a pathogenic point mutation. Conclusion: Imported recombinant RNAs can function as anti-replicative agents in human mitochondria. Significance: This is a new approach for therapy of mitochondrial diseases. Defects in mitochondrial genome can cause a wide range of clinical disorders, mainly neuromuscular diseases. Presently, no efficient therapeutic treatment has been developed against this class of pathologies. Because most of deleterious mitochondrial mutations are heteroplasmic, meaning that wild type and mutated forms of mitochondrial DNA (mtDNA) coexist in the same cell, the shift in proportion between mutant and wild type molecules could restore mitochondrial functions. Recently, we developed mitochondrial RNA vectors that can be used to address anti-replicative oligoribonucleotides into human mitochondria and thus impact heteroplasmy level in cells bearing a large deletion in mtDNA. Here, we show that this strategy can be also applied to point mutations in mtDNA. We demonstrate that specifically designed RNA molecules containing structural determinants for mitochondrial import and 20-nucleotide sequence corresponding to the mutated region of mtDNA, are able to anneal selectively to the mutated mitochondrial genomes. After being imported into mitochondria of living human cells in culture, these RNA induced a decrease of the proportion of mtDNA molecules bearing a pathogenic point mutation in the mtDNA ND5 gene.
The Curriculum: Theory and Practice

This successful text provides an overview of the major areas of curriculum theory. It offers teachers, student teachers and others the kind of understanding they need as a basis for the planning and execution of their work. Such an awareness has become even more important since The Curriculum was first published, because of the increased understanding which has been acquired in the intervening years, and the accelerating shift towards more centralised control of the curriculum, resulting in the 1988 Education Act and the establishment of The National Curriculum in the United Kingdom. The revisions which the author has made to this third edition reflect and take account of major changes in the educational climate.
Separate Cyclic AMP Sensors for Neuritogenesis, Growth Arrest, and Survival of Neuroendocrine Cells*

Background: Three cAMP sensors (PKA, Epac1/2, and NCS/Rapgef2) coexist in neuroendocrine cells. Their roles in differentiation require elucidation. Results: Epac2, PKA, and NCS/Rapgef2 independently gate signaling for growth arrest, cell survival, and neuritogenesis after GPCR-Gs engagement in PC12 cells. Conclusion: Parallel, insulated pathways effect cAMP-dependent neuroendocrine cell differentiation. Significance: Assays for parcellated cAMP signaling in neuroendocrine cells have a broad application for CNS drug discovery. Dividing neuroendocrine cells differentiate into a neuronal-like phenotype in response to ligands activating G protein-coupled receptors, leading to the elevation of the second messenger cAMP. Growth factors that act at receptor tyrosine kinases, such as nerve growth factor, also cause differentiation. We report here that two aspects of cAMP-induced differentiation, neurite extension and growth arrest, are dissociable at the level of the sensors conveying the cAMP signal in PC12 and NS-1 cells. Following cAMP elevation, neuritogenic cyclic AMP sensor/Rapgef2 is activated for signaling to ERK to mediate neuritogenesis, whereas Epac2 is activated for signaling to the MAP kinase p38 to mediate growth arrest. Neither action of cAMP requires transactivation of TrkA, the receptor for NGF. In fact, the differentiating effects of NGF do not require activation of any of the cAMP sensors protein kinase A, Epac, or neuritogenic cyclic AMP sensor/Rapgef2 but, rather, depend on ERK and p38 activation via completely independent signaling pathways. Hence, cAMP- and NGF-dependent signaling for differentiation are also completely insulated from each other. Cyclic AMP and NGF also protect NS-1 cells from serum withdrawal-induced cell death, again by two wholly separate signaling mechanisms, PKA-dependent for cAMP and PKA-independent for NGF.
WebDASC: a web-based dietary assessment software for 8-11-year-old Danish children.

BACKGROUND The present study describes the development and formative evaluation of the Web-based Dietary Assessment Software for Children (WebDASC). WebDASC is part of the OPUS project ('Optimal well-being, development and health for Danish children through a healthy New Nordic Diet') and was intended to measure dietary change resulting from a school-based intervention. METHODS WebDASC was developed as a self-administered tool that could be used by 8-11-year-old children with or without parent's aid. The development of WebDASC followed a prototyping approach: focus groups, informal interviews, literature review, and usability tests preceded its release. Special consideration was given to age-appropriate design issues. RESULTS In WebDASC an animated armadillo guides respondents through six daily eating occasions and helps them report foods and beverages previously consumed. A database of 1300 food items is available either through category browse or free text search, aided by a spell check application. A type-in format is available for foods not otherwise found through category browse or text search. Amount consumed is estimated by selecting the closest portion size among four different digital images. WebDASC includes internal checks for frequently forgotten foods, and the following features to create motivation: a food-meter displaying cumulative weight of foods reported, a most popular food ranking, and a computer game with a high score list. CONCLUSIONS WebDASC was developed as an intuitive, cost-effective, and engaging method to collect detailed dietary data from 8- to 11-year-old children. Preliminary testing demonstrated that it was well accepted among children.
Cost of outpatient endoscopic sinus surgery from the perspective of the Canadian government: a time‐driven activity‐based costing approach

The time‐driven activity‐based costing (TD‐ABC) method is a novel approach to quantify the costs of a complex system. The aim of this study was to apply the TD‐ABC technique to define the overall cost of a routine outpatient endoscopic sinus surgery (ESS) from the perspective of the Canadian government payer.
Probiotic manipulation of the chronic rhinosinusitis microbiome

Staphylococcus aureus (SA) is a key pathogenic component of the chronic rhinosinusitis (CRS) microbiome and is associated with increased disease severity and poor postoperative outcomes. Probiotic treatments potentially offer a novel approach to the management of pathogenic bacteria in these recalcitrant patients through supporting a healthy community of commensal species. This study aims to investigate the probiotic properties of Staphylococcus epidermidis (SE) against SA in a mouse model of sinusitis.
ADHD symptom presentation and trajectory in adults with borderline and mild intellectual disability.

BACKGROUND This study examined symptoms and lifetime course of Attention Deficit Hyperactivity Disorder (ADHD) in adults with borderline and mild Intellectual Disability (ID). METHOD A total of 48 adults with ID and ADHD were compared with 221 adults with ADHD without ID using the informant Barkley scale for childhood and adulthood symptoms. RESULTS The ADHD/ID group presented with greater severity of (adult and childhood) symptoms compared with the non-ID group. For the ADHD/non-ID group, most symptoms improved significantly from childhood to adulthood, whereas only two symptoms changed significantly for the ID group. Principal component analysis revealed scattered loading of different items into five components for the ADHD/ID group that were not consistent with the classic clusters of inattentive, hyperactive and impulsive symptoms. A negative correlation was found between severity of symptoms and IQ. CONCLUSIONS ADHD in adults with ID may have a more severe presentation and an uneven and less favourable pattern of improvement across the lifespan in comparison with adults without ID.
Placement, relocation and end of life issues in aging adults with and without Down's syndrome: a retrospective study.

BACKGROUND Aging adults with Down's syndrome (DS) experience more relocations and other life events than adults with intellectual disabilities aged 50 and older without DS. Age-related functional decline and the higher incidence of dementia were implicated as the contributing factors that led to relocation and nursing home placement. METHOD A retrospective study of adults with intellectual disabilities who were born prior to the year 1946 was conducted to analyse the number of relocations experienced over a 5- and 10-year period. The cohort consisted of 140 individuals (61 with DS between ages 50-71 years, and 79 without DS between ages 57-89 years) who had been referred to a diagnostic and research clinic. RESULTS Analyses revealed the number of relocations over a 5- and 10-year period were significantly greater in the DS group. Placement in a nursing home for end of life care was significantly higher in the DS group whereas the majority (90%) in the non-DS group remained in a group home setting. Mortality was significantly earlier in the DS group with the mean age at death to be 61.4 years compared with 73.2 years in the non-DS group. CONCLUSIONS The present results suggest that aging adults with DS encounter more relocations, and are more likely to have their final placement for end of life care in a nursing home. In contrast, the adults without DS were subjected to less relocation and remained in the same group home setting.
Working memory and executive function profiles of individuals with borderline intellectual functioning.

BACKGROUND The aim of the present study was to investigate the following issues: (1) Do students with borderline intellectual functioning have a pervasive pattern of impaired working memory skills across both verbal and visuo-spatial domains? (2) Is there evidence for impairment in executive function skills, and which tasks indicate greater deficits? and (3) Which executive function tasks can effectively identify students with low IQ from typically developing peers? METHOD Students with borderline intellectual functioning (low-IQ; IQ standard scores were between 70 and 85) were age-matched with typically developing students (IQ standard scores >95). They were administered a range of working memory and executive function measures. RESULTS The results show that students with low IQ have pervasive working memory and executive function deficits. Specifically, visuo-spatial working memory and the Sorting task were the best single predictors that reliably classified students with low IQ. CONCLUSIONS Implications for education are discussed in the context of appropriate diagnosis and support in the classroom.
'We've been through it all together': supports for parents with children with rare trisomy conditions.

BACKGROUND Parenting a child with a developmental disability can be a positive experience. A salient part of this outcome is support at the time of diagnosis and in an ongoing manner from immediate and extended family members. Studies are sparse on this topic for parents with a child with a rare trisomy condition. METHOD The present study examined the support needs of parents with a child or adult with a rare trisomy condition (n = 20). Participants were recruited from the Tracking Rare Incidence Syndromes (TRIS) project. The TRIS Family, Friends and Finances Protocol was the data collection instrument. The protocol included primarily open-ended items. Qualitative analyses were conducted to identify themes from the protocol and follow-up phone contacts. RESULTS Support from immediate and extended family members varied from very positive to participants-describing very negative interactions with specific individuals. Many in the sample reported affirming experiences with spouses and difficulties with grandparents and other extended family members. CONCLUSIONS Results both confirmed the literature and reflected the unique circumstances of the participants. It is critical to raise awareness of the similar and disparate support needs of this unique population, as the affected children are living longer and their families require continuing support to meet their and their children's needs.
Depression and anxiety in chronic rhinosinusitis

Both depression and anxiety have been suspected to impact quality of life adversely in patients with chronic rhinosinusitis (CRS). The objective of this work was to assess for the presence of anxiety and/or depression in the setting of CRS and to assess their impact on disease‐related quality of life by analyzing the correlation between the Rhinosinusitis Disability Index (RSDI) and the Hospital Anxiety and Depression score (HADS), as well as the Lund‐Kennedy nasal endoscopic scores.
Attention-deficit/hyperactivity disorder among children with and without intellectual disability: an examination across time.

BACKGROUND Children with intellectual and developmental disabilities are at heightened risk for mental disorders, and disruptive behaviour disorders appear to be the most prevalent. The current study is a longitudinal examination of attention-deficit/hyperactivity disorder (ADHD) among children with and without intellectual disability (ID) across ages 5 to 8. METHOD We assessed 228 5-year-old children, 87 with ID and 141 with typical development (TD), for clinical diagnoses using a structured interview. These interviews were conducted with mothers annually from child age 5 to 8. RESULTS Attention-deficit/hyperactivity disorder was over 3 times as prevalent in the ID group as in the TD group across ages 5, 6, 7 and 8. The diagnosis of ADHD tended to emerge earlier and was more stable in the ID group; however, the total number and relative frequency of ADHD symptoms endorsed appeared to be similar within the two groups across time. With respect to the developmental course, the trajectories of ADHD inattentive and hyperactive/impulsive symptoms over time were similar in the two groups. DISCUSSION Children with ID appear to be at heightened risk for ADHD and they may experience a longer and more persistent course of the disorder. These findings highlight the need for making interventions available for early treatment of this condition in children with ID.
Determinan Penyakit Stroke

Penyakit stroke merupakan penyebab kematian dan kecacatan kronik yang paling tinggi pada kelompok umur diatas usia 45 tahun terbanyak di Indonesia. Tujuan penelitian ini untuk mengidentifikasi determinan utama yang berhubungan dengan penyakit stroke pada masyarakat di kelurahan Kebon Kalapa Bogor. Analisis lanjut terhadap 1.912 responden subset baseline data penelitian “Studi Kohort Faktor Risiko Penyakit Tidak Menular” Data dikumpulkan dengan metode wawancara pada penduduk tetap di kelurahan Kebon Kalapa, Kecamatan Bogor Tengah, Bogor tahun 2012. Diagnosis stroke berdasarkan anamnesis dan pemeriksaan dokter spesialis syaraf. Variabel independen meliputi karakteristik sosiodemografi, status kesehatan dan perilaku berisiko. Data dianalisis dengan uji regresi logistik ganda. Penyakit stroke ditemukan pada 49 (2,6%) orang. Determinan utama stroke meliputi hipertensi (OR = 4,20; IK 95% = 2,20 – 8,03), penyakit jantung koroner (OR = 2,74; IK 95% = 1,51 – 4,99), diabetes melitus (OR = 2,89; IK 95% = 1,47 – 5,64), dan status ekonomi miskin (OR = 1,83 ; IK 95% = 1,03 – 3,33). Pencegahan penyakit stroke dilakukan dengan peningkatan edukasi (kampanye/penyuluhan) melalui pengendalian faktor risiko utama yaitu hipertensi dan pencegahan terjadinya penyakit degeneratif lain yaitu penyakit jantung koroner dan diabetes melitus. Stroke disease is the leading cause of death and chronic disabi lity in most over the age of 45 years in Indonesia. The aim of study was to identify the major determinants of stroke disease in Kebon Kalapa community in Bogor. A deep analyze was conducted in 1.912 respondents based on the subset of baseline data “Risk Factors Cohort Study of Non Communicable Diseases. ” Data was collected by interviews on Kebon Kalapa community, Bogor in 2012. Stroke diagnosis was determined by anamnesis and neu-rological examination with specialist. Independent variables were sociodemographic characteristics, health status and risk behavior. Data analysis was performed by multiple logistic regression test. This study revealed that stroke disease was found in 49 people (2.6%). The main determinant of stroke included hypertension (OR = 4.20; 95% CI = 2.20 – 8.03), coronary heart disease (OR = 2.74; 95% CI = 1.51 – 4.99), diabetes mellitus (OR = 2.89; 95% CI = 1.47 – 5.64), and low economic status (OR = 1.83; 95% CI = 1.03 – 3.33). Prevention of stroke should be done by increasing education (campaign) through the control of major risk factors of hypertension and prevention of other degenerative diseases are coronary heart disease and diabetes mellitus.
Functional Identification of Conserved Residues Involved in Lactobacillus rhamnosus Strain GG Sortase Specificity and Pilus Biogenesis*

Background: Lactobacillus rhamnosus GG produces pili assembled and anchored by two distinct sortases, SrtC and SrtA, respectively. Results: Residue substitution within the triple glycine (TG) motif of pilin proteins impacts sortase-mediated polymerization. Conclusion: The TG motif determines sortase specificity during pilus biogenesis in GG. Significance: These results help explain the signaling involved in the assembly and anchoring of sortase-dependent pili. In Gram-positive bacteria, sortase-dependent pili mediate the adhesion of bacteria to host epithelial cells and play a pivotal role in colonization, host signaling, and biofilm formation. Lactobacillus rhamnosus strain GG, a well known probiotic bacterium, also displays on its cell surface mucus-binding pilus structures, along with other LPXTG surface proteins, which are processed by sortases upon specific recognition of a highly conserved LPXTG motif. Bioinformatic analysis of all predicted LPXTG proteins encoded by the L. rhamnosus GG genome revealed a remarkable conservation of glycine residues juxtaposed to the canonical LPXTG motif. Here, we investigated and defined the role of this so-called triple glycine (TG) motif in determining sortase specificity during the pilus assembly and anchoring. Mutagenesis of the TG motif resulted in a lack or an alteration of the L. rhamnosus GG pilus structures, indicating that the TG motif is critical in pilus assembly and that they govern the pilin-specific and housekeeping sortase specificity. This allowed us to propose a regulatory model of the L. rhamnosus GG pilus biogenesis. Remarkably, the TG motif was identified in multiple pilus gene clusters of other Gram-positive bacteria, suggesting that similar signaling mechanisms occur in other, mainly pathogenic, species.
A prevalência da perda auditiva em uma população de idosos da cidade do Rio de Janeiro: um estudo seccional

Hearing loss in the elderly is one of the most frequent chronic diseases. AIM: to estimate the prevalence of hearing loss in a representative sample of elderly people (aged 65 or over) in the city of Rio de Janeiro. MATERIAL AND METHOD: a prospective, cross-sectional population-based study with 238 elderly people aged 65 years or more (198 women and 40 men). RESULTS: the prevalence of hearing loss was 39.4% (better ear) and 61.6% (worse ear) in the female group, 60% (better ear) and 77.5% (worse ear) in the male group, and 42.9% and 64.3% in the study population. Mild hearing loss was the most prevalent level of hearing loss. CONCLUSION: the prevalence of hearing loss in the study population was significant and in accordance with others relevant international epidemiological studies. Longitudinal studies are needed to better understand age-related hearing loss.
From vulnerable plaque to atherothrombosis

Plaque rupture precipitates approximately 75% of all fatal coronary thrombi. Therefore, the plaque prone to rupture is the primary focus of this review. The lipid‐rich core and fibrous cap are pivotal in the understanding of plaque rupture. Plaque rupture is a localized process within the plaque caused by degradation of a tiny fibrous cap rather than by diffuse inflammation of the plaque. Atherosclerosis is a multifocal disease, but plaques prone to rupture seem to be oligofocal at most.
Renin‐angiotensin system revisited

New components and functions of the renin‐angiotensin system (RAS) are still being unravelled. The classical RAS as it looked in the middle 1970s consisted of circulating renin, acting on angiotensinogen to produce angiotensin I, which in turn was converted into angiotensin II (Ang II) by angiotensin‐converting enzyme (ACE). Ang II, still considered the main effector of RAS was believed to act only as a circulating hormone via angiotensin receptors, AT1 and AT2. Since then, an expanded view of RAS has gradually emerged. Local tissue RAS systems have been identified in most organs. Recently, evidence for an intracellular RAS has been reported. The new expanded view of RAS therefore covers both endocrine, paracrine and intracrine functions. Other peptides of RAS have been shown to have biological actions; angiotensin 2–8 heptapeptide (Ang III) has actions similar to those of Ang II. Further, the angiotensin 3–8 hexapeptide (Ang IV) exerts its actions via insulin‐regulated amino peptidase receptors. Finally, angiotensin 1–7 (Ang 1–7) acts via mas receptors. The discovery of another ACE2 was an important complement to this picture. The recent discovery of renin receptors has made our view of RAS unexpectedly complex and multilayered. The importance of RAS in cardiovascular disease has been demonstrated by the clinical benefits of ACE inhibitors and AT1 receptor blockers. Great expectations are now generated by the introduction of renin inhibitors. Indeed, RAS regulates much more and diverse physiological functions than previously believed.
Seroprevalence of hepatitis B in two period birth cohorts of Bolivian children: effect of universal vaccination.

BACKGROUND Since 2000 universal routine immunization against the hepatitis B virus (HBV) was implemented in Bolivia. This study aimed to assess the seroprevalence of markers against HBV in two different birth cohorts (pre-universal vaccine cohort and post-universal vaccine cohort) from Cochabamba, Bolivia. METHODS We performed a school-based seroepidemiological survey (n = 424) of HBV in 2010 in the Cochabamba region. An ELISA test was used to measure antibodies to the hepatitis B surface antigen (anti-HBs IgG) and to the hepatitis B core antigen (anti-HBc IgG). RESULTS The prevalence of anti-HBs IgG in the pre-universal vaccine cohort was 5.8% (95% CI: 3.3-8.3%); it was higher in boys (9.1%), and those living in suburbs (9.7%). The anti-HBs IgG prevalence among post-universal vaccine cohort was 37.9% (95% CI: 28.5-48.1%), and was higher in children who spoke Quechua at home (51.0%), those living in suburbs (53.9%), and those born in 2005 (72.7%). Neither cohort showed differences relating to parental education. The prevalence of anti-HBc IgG was 1.1% among post-universal vaccine cohort and 1.2% among pre-universal vaccine cohort (p > 0.05). CONCLUSIONS This study identified a persistent low seroprevalence of hepatitis B infection in spite of a decade of universal immunization, and low long-term humoral immunity against HBV infection in vaccinated children in Cochabamba.