Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of oxidative abnormalities in the pathophysiology of Alzheimer's disease.

Several lines of evidence suggest that abnormalities in oxidative metabolism and specifically in mitochondria may play an important role in Alzheimer's disease. Abnormalities of oxidative metabolism exist in this disorder. They have been demonstrated in brain studied in vivo, ex vivo (biopsies), at autopsy, and in non-neural tissues including cultured cells. The abnormalities include a profound deficit in the activity of the ketoglutarate dehydrogenase complex (KGDHC), which is likely to lead to impaired metabolism of glutamate and might contribute to selective neuronal cell death by excitotoxic mechanisms as well as by direct effects on energy metabolism through its role in the tricarboxylic acid cycle. Abnormalities in oxidative metabolism may be related to the pathophysiology of Alzheimer's disease by plausible mechanisms for which there is evidence at least in model systems. Hypoxia is known to induce neuropsychological impairments analogous to those which occur in dementing syndromes. Brain, and specifically neurons, are likely to be particularly vulnerable to impairments of oxidative metabolism because of their demonstrated tight dependence on continuous oxidation of glucose to maintain their structure and function. Neuroanatomic studies as well as recent data from CT, PET, and SPECT scanning agree with formulations that suggest the brain areas of greatest vulnerability in Alzheimer's disease include those particularly sensitive to oxidative impairments. Although the mechanisms of accumulation of the classical neuropathological hallmarks of Alzheimer's disease (paired helical filaments, amyloid plaques) are not known, experimental data suggest that metabolic stresses may contribute to the accumulation of these materials. These data include the accumulation of immunoreactivity of anti-paired helical filament antibodies in cells exposed to a mitochondrial poison, the uncoupler CCCP. Impairments of oxidative metabolism are known to impair the metabolism of neurotransmitters involved in Alzheimer's disease; the synthesis of acetylcholine, which is characteristically involved, is exquisitely sensitive to oxidative abnormalities. Experimental evidence suggests that abnormalities of cellular calcium homeostasis, which have been demonstrated in Alzheimer cells, may mediate key deleterious effects of the abnormalities in oxidative metabolism in this disorder. Experimental studies in animals indicate that age potentiates the effects of inherent oxidative abnormalities on the brain, as does cerebrovascular disease. These observations might help to explain the increasing clinical expression of the gene for Alzheimer's disease with age. They are also in accord with difficulties in separating the role of vascular from that of inherent degenerative factors in dementia of later onset. Treatment with L-carnitine, a manipulation designed to mitigate consequences of a mitochondrial abnormality, normalized several non-mitochondrial abnormalities in cultured Alzheimer cells. (ABSTRACT TRUNCATED AT 400 WORDS)
Safety and efficacy of the MitraClip® system for severe mitral regurgitation

The MitraClip® system is a newer percutaneous device that has shown promising results but data on its safety and efficacy in low‐ and high‐surgical risk populations continues to evolve. We performed a systematic review of the published studies reporting the safety and efficacy of MitraClip® implantation for treatment of moderate to severe and severe mitral regurgitation (MR).
Do age‐associated DNA methylation changes increase the risk of malignant transformation?

Aging of the organism is associated with highly reproducible DNA methylation (DNAm) changes, which facilitate estimation of donor age. Cancer is also associated with DNAm changes, which may contribute to disease development. Here, we speculate that age‐associated DNAm changes may increase the risk of tumor initiation. Notably, when using epigenetic signatures for age‐estimations tumor cells are often predicted to be much older than the chronological age of the patient. We demonstrate that aberrant hypermethylation within the gene DNA methyltransferase 3A (DNMT3A) – which may contribute to initiation of acute myeloid leukemia (AML) – is particularly observed in AML samples that reveal significantly more age‐associated DNAm changes. The functional relevance of age‐associated DNAm changes remains to be elucidated, but they occur genome wide, in a highly reproducible manner, and most likely influence chromatin organization – and hence may favor acquisition of aberrant DNAm patterns contributing to cancer in the elderly.
Localization by kainic acid lesions of neurones transmitting the carotid chemoreceptor stimulus for respiration in rat.

1. An attempt has been made to test the hypothesis that in the nucleus of the tractus solitarius (NTS) in the rat, the most caudal region of synaptic terminals of the carotid sinus nerve, just caudal to the obex, represents mainly the site of synapse of chemoreceptor fibres from the carotid body. 2. Under halothane anaesthesia, the neurotoxin kainic acid was used to lesion this region and a second region, immediately rostral to obex, where terminals are thought to arise mainly from baroreceptor fibres of the carotid sinus nerve. 3. Measurements based on the distribution of fluorescent dye co‐injected with the kainic acid showed that the two groups of 100 nl microinjections were centered 0.82 mm apart and that the injectate spread through mean distances of 0.57 mm (caudal microinjections) and 0.52 mm (rostral microinjections). Nissl staining was used to determine cellular degeneration. The caudal lesions mostly involved ventrolateral and commissural subnuclei of NTS and the rostral lesions involved lateral and dorsolateral subnuclei. 4. Ventilatory sensitivity to hypoxia was tested under light halothane anaesthesia, 1 day after lesioning. To enhance the responses, the contralateral carotid sinus nerve was sectioned prior to experiments. Caudal lesions reduced the ventilatory response to inspired oxygen (20.9‐9.6% O2) by a mean of 67% and rostral lesions by 18% of the effect produced by carotid sinus nerve section on that side. Subsequent section of the carotid sinus nerve on the side of the NTS lesion confirmed that caudal lesions produced effects comparable to those of carotid body denervation; rostral lesions did not. 5. These results strongly support the hypothesis that chemoreceptor and baroreceptor afferent fibres in the carotid sinus nerve synapse at substantially separable sites in the nucleus of the tractus solitarius. The identification of the site in NTS caudal to the obex as the principal site of carotid chemoreceptor synapses places them close to but not upon respiratory premotor neurones of the same nucleus.
Optimizing Chemotherapy for Patients with Advanced Non-small Cell Lung Cancer

Platinum-based therapy remains the standard of care for the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). When combined with a third-generation agent, platinum-based doublets improve survival compared with the third-generation agent given alone. Controversy remains, however, regarding the relative risks and benefits of the third-generation agents. Four large phase III trials have addressed this question, with only one trial finding a survival benefit in one of the treatment arms. TAX 326 compared docetaxel-based therapy with vinorelbine/cisplatin, and found that survival, response, and quality of life outcomes all favoured the docetaxel/cisplatin regimen. Consistent benefits have been reported with this regimen in other studies. The non-platinum-based docetaxel/gemcitabine combination is an alternative for patients who are not suitable candidates for platinum-based therapy. Other results have shown that single-agent docetaxel is an appropriate option for elderly patients and those with poor performance status. Overall, the wealth of data with docetaxel in advanced NSCLC suggests that it plays an important role in first-line treatment and, as a single agent, can be considered a reasonable approach in elderly and frail patients.
Cumulative prenatal exposure to adversity reveals associations with a broad range of neurodevelopmental outcomes that are moderated by a novel, biologically informed polygenetic score based on the serotonin transporter solute carrier family C6, member 4 (SLC6A4) gene expression

Abstract While many studies focus on the association between early life adversity and the later risk for psychopathology, few simultaneously explore diverse forms of environmental adversity. Moreover, those studies that examined the cumulative impact of early life adversity focus uniquely on postnatal influences. The objective of this study was to focus on the fetal period of development to construct and validate a cumulative prenatal adversity score in relation to a wide range of neurodevelopmental outcomes. We also examined the interaction of this adversity score with a biologically informed genetic score based on the serotonin transporter gene. Prenatal adversities were computed in two community birth cohorts using information on health during pregnancy, birth weight, gestational age, income, domestic violence/sexual abuse, marital strain, as well as maternal smoking, anxiety, and depression. A genetic score based on genes coexpressed with the serotonin transporter in the amygdala, hippocampus, and prefrontal cortex during prenatal life was constructed with an emphasis on functionally relevant single nucleotide polymorphisms, that is, expression quantitative trait loci. Prenatal adversities predicted a wide range of developmental and behavioral alterations in children as young as 2 years of age in both cohorts. There were interactions between the genetic score and adversities for several domains of the Child Behavior Checklist (CBCL), with pervasive developmental problems remaining significant adjustment for multiple comparisons. Scores combining different prenatal adverse exposures predict childhood behavior and interact with the genetic background to influence the risk for psychopathology.
Dental Health and Mortality in People With End-Stage Kidney Disease Treated With Hemodialysis: A Multinational Cohort Study.

BACKGROUND Dental disease is more extensive in adults with chronic kidney disease, but whether dental health and behaviors are associated with survival in the setting of hemodialysis is unknown. STUDY DESIGN Prospective multinational cohort. SETTING & PARTICIPANTS 4,205 adults treated with long-term hemodialysis, 2010 to 2012 (Oral Diseases in Hemodialysis [ORAL-D] Study). PREDICTORS Dental health as assessed by a standardized dental examination using World Health Organization guidelines and personal oral care, including edentulousness; decayed, missing, and filled teeth index; teeth brushing and flossing; and dental health consultation. OUTCOMES All-cause and cardiovascular mortality at 12 months after dental assessment. MEASUREMENTS Multivariable-adjusted Cox proportional hazards regression models fitted with shared frailty to account for clustering of mortality risk within countries. RESULTS During a mean follow-up of 22.1 months, 942 deaths occurred, including 477 cardiovascular deaths. Edentulousness (adjusted HR, 1.29; 95% CI, 1.10-1.51) and decayed, missing, or filled teeth score ≥ 14 (adjusted HR, 1.70; 95% CI, 1.33-2.17) were associated with early all-cause mortality, while dental flossing, using mouthwash, brushing teeth daily, spending at least 2 minutes on oral hygiene daily, changing a toothbrush at least every 3 months, and visiting a dentist within the past 6 months (adjusted HRs of 0.52 [95% CI, 0.32-0.85], 0.79 [95% CI, 0.64-0.97], 0.76 [95% CI, 0.58-0.99], 0.84 [95% CI, 0.71-0.99], 0.79 [95% CI, 0.65-0.95], and 0.79 [95% CI, 0.65-0.96], respectively) were associated with better survival. Results for cardiovascular mortality were similar. LIMITATIONS Convenience sample of clinics. CONCLUSIONS In adults treated with hemodialysis, poorer dental health was associated with early death, whereas preventive dental health practices were associated with longer survival.
Tuning the properties of the bacterial membrane with aminoacylated phosphatidylglycerol

The bacterial envelope is a semi‐permeable barrier that protects the cell from the hostilities of the environment. To survive the ever‐changing conditions of their surroundings, bacteria need to rapidly adjust the biochemical properties of their cellular envelope. Amino acid (aa) addition to phosphatidylglycerol (PG) of the membrane is one of the mechanisms used by bacteria to lower the net negative charge of their cellular envelope, thereby decreasing its affinity for several antibacterial agents such as the cationic antimicrobial peptides (CAMPs) produced by the innate immune response during host infection. This process requires the activity of an integral membrane protein, called aa‐PG synthase (aaPGS), to transfer the aa of aminoacyl‐tRNA (aa‐tRNA) onto the PG of the membrane. aaPGSs constitute a new family of virulence factors that are found in a wide range of microorganisms. aa‐PGs not only provide resistance to CAMPs but also to other classes of antibacterial agents and to environmental stresses such as those encountered during extreme osmotic or acidic conditions. This review will describe the known biochemical properties of aa‐PGSs, their specificity for aa‐tRNAs and phospholipids, and the growing repertoire of aa used as substrates by these enzymes. Their prevalence in bacteria and the phenotypes and modulations of membrane properties associated with these molecules will be addressed, as well as their regulation as a component of the envelope stress response system in certain bacteria. © 2009 IUBMB IUBMB Life, 61(10): 940–953, 2009
Transmission line pulse (TLP) testing of radio frequency (RF) micro-machined micro-electromechanical systems (MEMS) switches

Radio frequency micro-electromechanical (RF-MEM) switches, both ohmic and capacitive, are important for future RF wired and wireless communication systems. In this paper, transmission line pulse testing and ESD characterization is shown for the first time. A new TLP methodology, an extension to classical TLP plot analysis, is presented and it is demonstrated as this new technique is necessary to correctly investigate the TLP response of RF-MEMS switches.
Significantly lower levels of hypoxanthine and creatinine in the CSF of patients with schizophrenia

Levels of hypoxanthine, xanthine, uric acid (UA), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and creatinine were measured in the cerebrospinal fluid (CSF) of 49 patients with schizophrenia and 21 healthy controls. Twenty-six of the patients were first admissions who had never received antipsychotic treatment. We found significantly lower levels of hypoxanthine in the CSF of the patients (p=0.02) – the mean±SD was 3.09±0.57 μmol/l for controls and 2.72±0.69 μmol/l for patients with schizophrenia. Female schizophrenics had significantly lower levels of creatinine in their CSF than controls (p=0.01) –the mean±SD was 3.04±0.56 μmol/l for female controls and 2.67±0.74 μmol/l for females with schizophrenia. There were also numerous positive correlations between the substances in the CSF. But these positive correlations between metabolites in the CSF need to be interpreted with caution as it could be caused by a similar grade of dilution. The finding of lowered levels of hypoxanthine in schizophrenia is interesting in the light of the purine hypothesis of schizophrenia – which proposes that schizophrenia, at least in part, may be caused by an imbalance in adenosine signaling. But also because of the recent interest the xanthine-oxidase inhibitor, and hypoxanthine isomer, allopurinol has gained as an adjuvant treatment in schizophrenia.
Connexins and E‐cadherin are differentially expressed during trophoblast invasion and placenta differentiation in the rat

We have characterized the spatial and temporal expression pattern of six different connexin genes and E‐cadherin during trophectoderm development in the rat. During the initial phase of trophoblast invasion at 6 days postcoitum (dpc), the trophoblast expressed E‐cadherin but no connexin expression could be observed. With progressing invasion of the polar trophoblast into the maternal decidua, from 7 dpc onwards E‐cadherin expression in the ectoplacental cone cells was lost and was now restricted to the extraembryonic ectoderm. In the ectoplacental cone and extraembryonic ectoderm instead connexin31 mRNA and protein could be found. This pattern was maintained up to day 10 postcoitum. The start of labyrinthine trophoblast differentiation from day 11 postcoitum onwards was characterized by persisting expression of E‐cadherin in the extraembryonic ectoderm and its derivative, the chorionic plate. In addition to E‐cadherin, from 10 dpc onwards, connexin26 started to be expressed in the chorionic plate, and both molecules remained coexpressed in the labyrinthine trophoblast of the mature placenta. During this differentiation process connexin31 remained expressed mainly in the proliferating spongiotrophoblast. From day 14 postcoitum onwards, the expression of connexin31 in the spongiotrophoblastic cells decreased, and in parallel they started to express connexin43. The trophoblastic giant cells, first characterized by connexin31, lost all of the investigated connexins during midgestation on day 12 postcoitum but started to express connexin43 from day 18 postcoitum onwards. Our studies suggest that loss of E‐cadherin and induction of connexin31 expression is correlated with the proliferative and invasive stages of the ectoplacental cone, whereas appearance of connexin26, E‐cadherin and connexin43 reflects the switch to the differentiated phenotypes of the mature placenta. © 1996 Wiley‐Liss, Inc.
Situation ethics.

The situation ethics that we provide for you will be ultimate to give preference. This reading book is your chosen book to accompany you when in your free time, in your lonely. This kind of book can help you to heal the lonely and get or add the inspirations to be more inoperative. Yeah, book as the widow of the world can be very inspiring manners. As here, this book is also created by an inspiring author that can make influences of you to do more.
The role of dietary protein in hepatic lipogenesis in the young rat

1. The effect of varying dietary levels of casein (40–140 g/kg) on hepatic lipogenesis and the levels of hepatic fatty acid synthetase (FAS), glucose-6-phosphate dehydrogenase (EC 1.1.1.49; G6PD), malic enzyme (EC 1.1.1.40; ME), citrate cleavage enzyme (EC 4.1.3.8;CCE), acetyl CoA carboxylase (EC 6.4.1.2; AcCx), glucokinase (EC 2.7.1.2; GK), and pyruvate dehydrogenase (PDH) was examined in young, growing rats. 2. The activities of AcCx, FAS, G6PD and in vivo fatty acid synthesis were generally found to increase with increased dietary protein. 3. The levels of GK and PDH were not related to dietary protein. 4. ME decreased with increasing dietary protein. 5. The results demonstrate a dissociation between hepatic fatty acid synthesis and ME and suggest that when rats consume low-protein diets the NADPH needed for fatty acid synthesis is generated primarily by ME but that as the level of dietary protein is increased the contribution of ME is reduced while that of the phosphogluconate pathway becomes more important.
Sporothrix schenckii Lipid Inhibits Macrophage Phagocytosis: Involvement of Nitric Oxide and Tumour Necrosis Factor‐α

The role of cell‐wall compounds in the immune response to sporotrichosis is unknown. The effect of cell‐wall compounds and exoantigen obtained from Sporothrix schenckii in macrophage/fungus interaction was analysed with respect to nitric oxide (NO) and tumour necrosis factor‐α (TNF‐α). The lipid compound of the cell wall plays an important role in the pathogenesis of this mycosis and was found to inhibit the phagocytic process and to induce high liberation of NO and TNF‐α in macrophage cultures in the present study. This is a very interesting result because it is the first report about one compound of the fungus S. schenckii that presents this activity.
Wave digital filters: Theory and practice

Wave digital filters (WDFs) are modeled after classical filters, preferably in lattice or ladder configurations or generalizations thereof. They have very good properties concerning coefficient accuracy requirements, dynamic range, and especially all aspects of stability under finite-arithmetic conditions. A detailed review of WDF theory is given. For this several goals are set: to offer an introduction for those not familiar with the subject, to stress practical aspects in order to serve as a guide for those wanting to design or apply WDFs, and to give insight into the broad range of aspects of WDF theory and its many relationships with other areas, especially in the signal-processing field. Correspondingly, mathematical analyses are included only if necessary for gaining essential insight, while for all details of more special nature reference is made to existing literature.
A Case Study Investigating a Behavioural Intervention to Reduce Caffeine Consumption

This case study investigated a behavioural intervention to reduce caffeine consumption in a 50-year-old female with a 35-year history of consuming >350 mg caffeine per day. The participant completed a behaviour diary for 10-weeks, recording amount of caffeine consumed, type of caffeinated drink, time, location, who she was with and the activity in which she was engaged. She also completed a 10-point performance scale, and recorded tiredness and headaches. Baseline data was recorded for one week, and then Functional Behavioural Analysis of the diary data was used to design an intervention. A graduated intervention was implemented: Stage 1 (1-week), caffeine<=160 mg/day; Stage 2 (1-week), caffeine<=80 mg/day; Stage 3 (7-weeks), caffeine<=35 mg/day. Caffeine was reduced to planned levels during the intervention period. Perceived performance ratings were significantly improved during the three stages of the intervention relative to baseline (p<0.05). Frequency of daily tiredness increased during Stage 2 and decreased overall during Stage 3 relative to baseline. Headaches were at least as frequent during the intervention as they were during baseline. Findings suggest that the intervention was successful over this 2-month period. Further monitoring is recommended in order to ascertain whether headaches and tiredness (possibly symptoms of caffeine withdrawal) persist.
Exploring lesbian, gay and bisexual patients’ accounts of their experiences of cancer care in the UK

Despite greater recognition of rights and responsibilities around the care of cancer patients who identify as lesbian, gay or bisexual (LGB) within healthcare systems in the United Kingdom, recent quantitative evidence suggests that they experience poorer care than heterosexual counterparts and qualitative findings are limited. Therefore, in the present study, we present an analysis of the accounts of fifteen British LGB cancer patients (diagnosed with different forms of the disease) of the care received. Data were collected through in-depth individual interviews and analysed using thematic analysis. Three of the emerging themes are discussed. These include an examination of what we conceptualise as the 'awkward choreography around disclosure' opportunities and dilemmas for LGB patients, we describe 'making sense of sub-optimal care' which included instances of overt discrimination but was more frequently manifested through micro-aggressions and heteronormative systems and practices, and explore accounts of 'alienation from usual psychosocial cancer support'. We employ Meyer's Minority Stress Theory (2003) as a lens to interrogate the data and explore the ways in which actual or anticipated prejudice affected their experiences of treatment and support. We close with recommendations to enhance LGB-affirmative cancer care including enhanced training of healthcare professionals and explicit articulation of institutional commitment to LGB equality.