Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanisms of hypoglycaemia related sudden cardiac death in type 2 diabetes mellitus

1 Declaration . 11 Publications Resulting from this Work. 12 Acknowledgements . 15 List of Tables . 17 List of Figures . 19 List of Abbreviations . 23 Chapter 1 Introduction. 26 1.1 Pathogenesis of Type 2 Diabetes . 28 1.2 Pathophysiology of Sudden Cardiac Death . 32 1.2. 1 Atherogenesis . 34 1.2. 2 Vulnerable Plaques . 34 1.2. 3 Thrombosis and Coronary Occlusion . 35 1.2. 4 Cardiac Electrical Instability and Arrhythmogenesis. 36 1.3 Type 2 Diabetes and Cardiovascular Disease: Role of Glycaemia and Other Risk Factors . 38 1.3. 1 Risk Factors for Cardiovascular Disease in Type 2 Diabetes . 39 1.3. 2 Mechanisms of Diabetic Cardiovascular Disease . 43 1.3. 3 The Contribution of Glycaemia to CVD in Type 2 Diabetes . 49 1.4 Intensive Glycaemic Control and Cardiovascular Mortality in Type 2 diabetes . 50 1.5 Can Hypoglycaemia be a Potential Mechanism for Increased Cardiovascular Death Observed with Intensive Glycaemic Control in Type 2 Diabetes Patients . 56 1.5. 1 Strength of Association . 58 1.5. 2 Consistency with Other Studies . 59 1.5. 3 Dose Response. 60
Patterns and determinants of leisure participation of youth and adults with developmental disabilities.

BACKGROUND People with developmental disabilities are at high risk for a limited participation in leisure activities. The aim of this study was to investigate the participation in, preference for and interest in leisure activities of young and adults with developmental disabilities, and to examine the factors associated with leisure activity. METHODS A cross-sectional design was used with a convenience sample of 237 people aged 17 to 65, living in the community. Leisure participation was assessed with the Spanish version of Leisure Assessment Inventory. Percentages were calculated by types of activity, and repeated measures anovas were used to analyse the differences between types of activities, and mixed anovas to analyse the factors that explain differences in leisure activity participation, preference and interest. RESULTS Leisure social activities and recreation activities at home were mostly solitary and passive in nature and were identified as those being most commonly engaged in. Respondents expressed preference for more social and physical activity, and they were interested in trying out a large number of physical activities. Age and type of schooling determine participation in leisure activity. The results underscore the differences in leisure activity participation, preference and interest depending on the severity of the disability. CONCLUSIONS The findings reveal interesting patterns of participation in leisure activities from the viewpoint of youngsters and adults with developmental disabilities. Leisure participation among people with developmental disabilities is likely to be more affected by environmental factors than by personal factors.
EVALUATION OF POTENTIAL HEALTH BENEFITS OF TWO NOVEL SPECIAL FOODS IN LIVER CIRRHOTIC PATIENTS

Two therapeutic diets have been formulated (A & B) and prepared in bakery form for patients with liver cirrhosis. The formulation was based on the presence of protein of high Fisher ratio and fat rich in medium chain triglycerides. Both formulas contained edible sources of antioxidants. Honey was added as a sweetener. Proximate analysis of Formula B and its contents of amino acids and fatty acids were carried out. Formula A was analysed in previous research for the same above mentioned composition. The two formulas were sensory evaluated by liver cirrhotic patients. Potential benefits of both formulas in addition of nutritional advice were evaluated in liver cirrhotic patients. Biochemical parameters reflecting liver function (plasma AST, ALT, ALP, total bilirubin, direct bilirubin and ammonia), oxidative stress (plasma NO and MDA) and nutritional status (plasma total protein, albumin, globulin and A/G ratio) were studied before and after two months of dietary intervention. The nutritional status of patients was evaluated through anthropometric measurements, food intake and selected biochemical parameters. Proximate analysis results showed that formula B contain 17.6% protein and 7.5% fat. Amino acids analysis of the same formula showed that its Fisher ratio was 2.49. GC analysis of fatty acids revealed that medium chain fatty acids constitute 38.6% of total fatty acids. The results of sensory evaluation showed that overall score of formula A was significantly higher than that of formula B. Nutritional status determined through triceps skin fold at the start of the clinical study showed 38% of cases were normal, 8% were severely malnourished and 54% over normal. Analysis of mean dietary intake of patients in the beginning of the study revealed that all liver cirrhotic patients were hypo-caloric. All estimated nutrients were lower than RDA except for protein. Mean dietary intake of patient after two months of the study revealed that all patients increased their caloric intake however they were still hypo-caloric. Comparing biochemical parameters of patients before and after dietary intervention of either formulas and nutritional advice revealed that all parameters reflecting liver dysfunction were non significantly improved. However AST activity significantly decreased on supplementation of diet A. A significant increase in plasma albumin and total protein was noticed in patients after both dietary interventions which may reflect some improvements in liver synthetic function and nutritional status. Ammonia was only significantly decreased in patients given formula A. Nitric oxide and MDA were significantly reduced in both dietary interventions with different degrees. In conclusion, both dietary interventions in addition of dietary advice in the present study have beneficial effects towards liver cirrhotic patients concerning reduction of oxidative stress and inflammation. Formula A was superior in reducing plasma AST activity and ammonia level.
Death by mental retardation? The influence of ambiguity on death certificate coding error for adults with intellectual disability.

BACKGROUND Although the coding of mental retardation as underlying cause of death has been recognised by previous researchers as erroneous, factors influencing this inaccuracy have not been sufficiently analysed. This study explores the effects of diagnostic ambiguity on risk of mental retardation being coded as underlying cause of death on US death certificates from 2004. METHODS Utilising all US death certificates from 2004 that included a cause of death code for mental retardation, logistic regression analysis provided estimates of the likelihood of having mental retardation erroneously coded as the underlying cause of death. Estimators used to measure ambiguity included the number of multiple causes of death, the place of death, and ICD-10 diagnostic Chapter codes. RESULTS A total of 2278 US death certificates from 2004 included a cause of death code for mental retardation. Of these death certificates, 20% erroneously coded mental retardation as the underlying cause of death. Reflecting the negative impact of diagnostic ambiguity on death certificate coding accuracy, mental retardation was more likely to be coded as underlying cause of death for decedents who: (1) had a death certificate that provided less information on co-morbid disease processes; (2) died in an outpatient or emergency room setting; or (3) had either abnormal symptomatology or death by injury, accident or other external cause. CONCLUSIONS Findings from this study, as well as prior research, demonstrate that attempts to understand mortality trends for this population must attend to frequent underlying cause of death coding errors which threaten accuracy of cause of death data. Furthermore, inquiry is warranted into the impetus behind US death certificate coding policy that continues to allow the erroneous coding of 'death by mental retardation'.
The Nuclear Pore Complex Function of Sec13 Protein Is Required for Cell Survival during Retinal Development*

Background: Sec13 is a core component in both the protein trafficking complex and the nuclear pore complex (NPC). Results: The role of Sec13 in retina development has been investigated. Conclusion: The NPC function of Sec13 is essential for retina development. Significance: This is the first genetic evidence to differentiate the contributions of the two functions of Sec13 during organogenesis. Sec13 is a dual function protein, being a core component of both the COPII coat, which mediates protein trafficking from the endoplasmic reticulum to the Golgi apparatus, and the nuclear pore complex (NPC), which facilitates nucleo-cytoplasmic traffic. Here, we present a genetic model to differentiate the roles of these two functions of Sec13 in vivo. We report that sec13sq198 mutant embryos develop small eyes that exhibit disrupted retinal lamination and that the mutant retina contains an excessive number of apoptotic cells. Surprisingly, we found that loss of COPII function by oligonucleotide-mediated gene knockdown of sec31a and sec31b or brefeldin A treatment did not disrupt retinal lamination, although it did result in digestive organ defects similar to those seen in sec13sq198, suggesting that the digestive organ defects observed in sec13sq198 are due to loss of COPII function, whereas the retinal lamination defects are due to loss of the NPC function. We showed that the retinal cells of sec13sq198 failed to form proper nuclear pores, leading to a nuclear accumulation of total mRNA and abnormal activation of the p53-dependent apoptosis pathway, causing the retinal defect in sec13sq198. Furthermore, we found that a mutant lacking Nup107, a key NPC-specific component, phenocopied the retinal lamination phenotype as observed in sec13sq198. Our results demonstrate a requirement for the nuclear pore function of Sec13 in development of the retina and provide the first genetic evidence to differentiate the contributions of the NPC and the COPII functions of Sec13 during organogenesis.
Platelet-derived Growth Factor β-Receptor, Transforming Growth Factor β Type I Receptor, and CD44 Protein Modulate Each Other's Signaling and Stability*

Background: The hyaluronan receptor CD44 interacts with the PDGF β-receptor and the TGFβ type I receptor. Results: CD44, PDGF β-receptor and TGFβ type I receptor affect each other's signaling, stability and function. Conclusion: Cross-talk between PDGF β-receptor and TGFβ type I receptor occurs in human dermal fibroblasts. Significance: This study reveals novel modulatory mechanisms of PDGF and TGFβ signaling. Growth factors, such as platelet-derived growth factor BB (PDGF-BB) and transforming growth factor β (TGFβ), are key regulators of cellular functions, including proliferation, migration, and differentiation. Growth factor signaling is modulated by context-dependent cross-talk between different signaling pathways. We demonstrate in this study that PDGF-BB induces phosphorylation of Smad2, a downstream mediator of the canonical TGFβ pathway, in primary dermal fibroblasts. The PDGF-BB-mediated Smad2 phosphorylation was dependent on the kinase activities of both TGFβ type I receptor (TβRI) and PDGF β-receptor (PDGFRβ), and it was prevented by inhibitory antibodies against TGFβ. Inhibition of the activity of the TβRI kinase greatly reduced the PDGF-BB-dependent migration in dermal fibroblasts. Moreover, we demonstrate that the receptors for PDGF-BB and TGFβ interact physically in primary dermal fibroblasts and that stimulation with PDGF-BB induces internalization not only of PDGFRβ but also of TβRI. In addition, silencing of PDGFRβ by siRNA decreased the stability of TβRI and delayed TGFβ-induced signaling. We further show that the hyaluronan receptor CD44 interacts with both PDGFRβ and TβRI. Depletion of CD44 by siRNA increased signaling via PDGFRβ and TβRI by stabilizing the receptor proteins. Our data suggest that cross-talk between PDGFRβ and TβRI occurs in dermal fibroblasts and that CD44 negatively modulates signaling via these receptors.
Prevalence and predictors of hypoxaemia in respiratory and non-respiratory primary diagnoses among emergently ill children at a tertiary hospital in south western Nigeria.

BACKGROUND Hypoxaemia is a potentially harmful complication of both acute lower respiratory tract infections (ALRI) and non-ALRI in children but its contribution to burden and outcomes of hospital admissions in Africa is unclear. We investigated prevalence and predictors of hypoxaemia in ALRI and non-ALRI according to age and primary diagnoses in emergently ill children in south western Nigeria. METHODS In 1726 emergently ill children admitted to a tertiary hospital in Ibadan, south western Nigeria, oxygen saturation was measured shortly after admission. Hypoxaemia was defined as oxygen saturation <90%. Clinical features and the primary admission diagnoses were recorded. Prevalence of hypoxaemia according to age and diagnoses was calculated. Symptoms and signs associated with hypoxaemia were compared between children with ALRI and those with non-ALRI. RESULTS Hypoxaemia was detected in 28.6% (494/1726) of admissions. Prevalence of hypoxaemia varied in different conditions: it was 49.2% (154/313) in ALRI, 41.1% (188/454) in neonates, 27.2% (6/22) in post-neonatal tetanus, 23.3% (14/60) in sickle cell anaemia, 22.6% (38/168) in septicaemia and 14.4% (76/527) of malaria cases. Nasal flaring (OR 3.86; 95% CI 1.70 to 8.74) and chest retraction (OR 4.77; 95% CI 1.91 to 11.92) predicted hypoxaemia in ALRI but not in non-ALRI. CONCLUSIONS Hypoxaemia is common among Nigerian children admitted to an emergency unit and is associated with a poor outcome irrespective of primary admission diagnosis. Provision of equipment to measure oxygen saturation and facilities for effective oxygen delivery might substantially reduce mortality.
Adjustment Disorders (Stress Related or Psychiatric Disorder)

Adjustment disorder is a stress-related, short-term, nonpsychotic disturbance associated with impairment in some element of general functioning of patients because their emotional or behavioral response to an identifiable stressful event or change in the person’s life [1]. The disorder usually begins within 3 months of the stressful event and should subside when the stressor resolves or the person has adapted to the change, usually within 6 months [1]. Adjustment disorders constitute a diagnostic category that lies between health and pathology. Adjustment disorders are located on a continuum between normal stress reactions and specific psychiatric disorders. A number of studies have reported rates around 12% across a variety of populations. In clinical patient populations, rates as high as 23% have been recorded [2-8]. Depressed mood was the most common subtype assigned (11.6%), followed by anxious mood, mixed anxiety and depressed mood, and disturbance of conduct [9-15]. According to DSM-5, a principal diagnosis of adjustment disorder is made in approximately 5-20% of individuals undergoing outpatient mental health treatment. In the setting of a hospital psychiatric consultation service, adjustment disorder is often the most common diagnosis, with frequencies as high as 50% [1]. Most studies report no significant differences in prevalence among age groups [5,16-19]. Approximately half of the patients with adjustment disorder suffered from depressed/irritable mood (59%), sleep disturbances (48%), and poor performance in school (48%).
Two Experimental Strategies to Restore Muscle Mass in Adult Rats Following Spinal Cord Injury

Spinal cord injury decreases muscle mass and is associated with myofiber type trans formations in skeletal muscles. The present study evaluated the potential of motor- assisted cycling exercise or transplantation of fetal spinal cord tissue into the lesion cavity to inhibit or minimize these changes in skeletal muscles of 27 adult female Sprague-Dawley rats. Soleus (SO) and tibialis anterior (TA) muscles were studied 30 to 32 days after injury/intervention in the following groups: uninjured control ani mals (Con); spinal cord injured only (Tx); Tx with a 4-week exercise program con sisting of five weekly 60-minute sessions of cycling exercise initiated 5 days after in jury (TxEx); and Tx with fetal spinal cord tissue transplanted into the lesion cavity at the time of injury (TxTp). SO and TA muscle to body weight ratios were reduced significantly in the Tx group (24-30% decrease vs Con, p < 0.05) but were maintained with regular cycling exercise (6-8% decrease vs Con, no significant difference). The transplant had a beneficial effect on TA muscle mass (16% decrease vs Con, no sig nificant difference) but was not effective in limiting the effects of Tx on SO muscle mass. Immunohistochemistry and Northern analysis of TA and SO muscles revealed a Tx-induced reduction in myofiber cross sectional area (22% and 33% vs Con re spectively, p < 0.05) as well as a conversion in myosin heavy chain (MyHC) expres sion toward faster MyHC isoforms. Moreover, one month after injury, there was an increase in myofibers expressing more than one MyHC. mRNA encoding MyoD, a muscle-specific transcription factor, was increased in SO muscles suggesting that it may be involved in the long-term adaptations following spinal cord transection. Although cycling exercise was effective in preventing the decrease in myofiber area in both TA and SO, it did not inhibit the transformations of myofiber type. TA myofiber area was maintained in transplant recipients, however, this treatment was without conse quence on the size of SO myofibers. These results suggest that some of the normally observed spinal cord injury-induced skeletal muscle adaptations are minimized after one month of cycling exercise or fetal spinal cord tissue transplants. Key Words: Myosin heavy chain—Exercise—MyoD—Fetal tissue transplantation—Fiber types.
A five-year field assessment of rapid diagnostic tests for meningococcal meningitis in Niger by using the combination of conventional and real-time PCR assays as a gold standard.

BACKGROUND Meningococcocal meningitis represents an important cause of mortality and morbidity in sub-Saharan countries. Confirmatory bacteriological or molecular diagnosis is essential for patient management/treatment and meningitis surveillance, but many laboratory tests are expensive and rarely available for low-income countries. A rapid diagnostic test (RDT) represents a valuable alternative to improve case management and surveillance. METHODS A dipstick RDT developed in early 2000s that detects Neisseria meningitidis serogroups A, C, W and Y but for which a new conjugated antibody (L4-8) for the detection of serogroup A replaced the original K15-2 was assessed in the field by trained staff from health centres and district hospitals in Niger. The results were compared to those obtained in the reference laboratory and the sensitivity and specificity of RDTs were determined using conventional and real-time PCR assays as a gold standard. RESULTS RDT results from field staff and the reference laboratory obtained for 2095 cerebrospinal fluid (CSF) specimens presented a strong concordance of 94% with Cohen's κ coefficient of 0.88. The observed concordance between RDTs operated by staff from the reference laboratory vs combination of conventional and real-time PCR assays was 89% with Cohen's κ coefficient of 0.76 indicating very good agreement. The theoretical overall sensitivity for RDT was 91.5% and the specificity 84.6%. CONCLUSIONS RDT has proven to be relatively sensitive and specific for the detection of meningococcal serogroups A/C/Y/W. We confirmed that these RDTs can be reliably operated by trained but non-specialised staff in basic health facilities.
Immersive virtual reality as a teaching tool for neuroanatomy

Three‐dimensional (3D) computer modeling and interactive virtual reality (VR) simulation are validated teaching techniques used throughout medical disciplines. Little objective data exists supporting its use in teaching clinical anatomy. Learner motivation is thought to limit the rate of utilization of such novel technologies. The purpose of this study is to evaluate the effectiveness, satisfaction, and motivation associated with immersive VR simulation in teaching medical students neuroanatomy.
Kinetics, Structure, and Mechanism of 8-Oxo-7,8-dihydro-2′-deoxyguanosine Bypass by Human DNA Polymerase η*♦

Background: 8-OxoG is a major oxidative lesion in DNA and is associated with cancer. Results: Kinetic and mass spectrometric studies demonstrate that human polymerase η bypasses 8-oxoG in a largely error-free manner. Conclusion: Arginine 61 from the finger domain plays a key role in error-free bypass at the insertion stage. Significance: In addition to photo-adducts and cisplatinated DNA, polymerase η might also be involved in accurate bypass of 8-oxoG in vivo. DNA damage incurred by a multitude of endogenous and exogenous factors constitutes an inevitable challenge for the replication machinery. Cells rely on various mechanisms to either remove lesions or bypass them in a more or less error-prone fashion. The latter pathway involves the Y-family polymerases that catalyze trans-lesion synthesis across sites of damaged DNA. 7,8-Dihydro-8-oxo-2′-deoxyguanosine (8-oxoG) is a major lesion that is a consequence of oxidative stress and is associated with cancer, aging, hepatitis, and infertility. We have used steady-state and transient-state kinetics in conjunction with mass spectrometry to analyze in vitro bypass of 8-oxoG by human DNA polymerase η (hpol η). Unlike the high fidelity polymerases that show preferential insertion of A opposite 8-oxoG, hpol η is capable of bypassing 8-oxoG in a mostly error-free fashion, thus preventing GC→AT transversion mutations. Crystal structures of ternary hpol η-DNA complexes and incoming dCTP, dATP, or dGTP opposite 8-oxoG reveal that an arginine from the finger domain assumes a key role in avoiding formation of the nascent 8-oxoG:A pair. That hpol η discriminates against dATP exclusively at the insertion stage is confirmed by structures of ternary complexes that allow visualization of the extension step. These structures with G:dCTP following either 8-oxoG:C or 8-oxoG:A pairs exhibit virtually identical active site conformations. Our combined data provide a detailed understanding of hpol η bypass of the most common oxidative DNA lesion.