Miracle-dz/UniFAR-FTUs huggingface dataset:
Photo-damage, photo-protection and age-related macular degeneration

Age-related macular degeneration (AMD) is a degenerative retinal disease that causes blindness in people 60–65 years and older, with the highest prevalence appearing in people 90 years-old or more. Epidemiological estimates indicate that the number of cases is increasing, and will almost double in the next 20 years. Preventive measures require precise etiological knowledge. This is quite difficult, since AMD is a multifactorial condition with intricate relationships between causes and risk factors. In this review, we describe the impact of light on the structure and physiology of the retina and the pigment epithelium, taking into account the continuous exposure to natural and artificial light sources along the life of an individual. A large body of experimental evidence demonstrates the toxic effects of some lighting conditions on the retina and the pigment epithelium, and consensus exists about the importance of photo-oxidation phenomena in the causality chain between light and retinal damage. Here, we analyzed the transmission of light to the retina, and compared the aging human macula in healthy and diseased retinas, as shown by histology and non-invasive imaging systems. Finally, we have compared the putative retinal photo-sensitive molecular structures that might be involved in the genesis of AMD. The relationship between these compounds and retinal damage supports the hypothesis of light as an important initiating cause of AMD.
Failure of treatment with first-line lopinavir boosted with ritonavir can be explained by novel resistance pathways with protease mutation 76V.

BACKGROUND Virological failure of first-line antiretroviral therapy based on lopinavir boosted with ritonavir (lopinavir/r) has rarely been associated with resistance in protease. We identified a new genotypic resistance pathway in 3 patients who experienced failure of first-line lopinavir/r treatment. METHODS Viral protease and the C-term part of Gag were sequenced. The observed mutations were introduced in a reference strain to investigate impact on protease inhibitor susceptibility and replication capacity. RESULTS A detailed longitudinal analysis demonstrated the selection of the M46I+L76V protease mutations in all 3 patients. The L76V conferred a solitary 3.5-fold increase in one-half the maximal inhibitory concentration to lopinavir but severely hampered viral replication. Addition of M46I, which did not confer any lopinavir resistance on its own, had a dual effect. It partly compensated for the loss in replication capacity and increased the one-half maximal inhibitory concentration to above the lower clinical cutoff (11-fold). Analysis of a large clinical database (>180,000 human immunodeficiency virus [HIV] sequences) demonstrated a significant association (Spearman rho, 0.93) between the increased presence of L76V in clinical samples (0.5% in 2000 to 3.4% in 2006) and lopinavir prescription over time. CONCLUSIONS The HIV protease substitution L76V, in combination with M46I, confers clinically relevant levels of lopinavir resistance and represents a novel resistance pathway to first-line lopinavir/r therapy.
Vasomotor reactivity in dementia of alzheimer type

The objective of this study was to examine the cerebral blood flow and the vasomotor function of CO2‐responsive intracerebral vessels in Alzheimer's disease. Patients met DSM‐III‐R criteria for dementia of Alzheimer type and had neither symptoms nor signs of cardiovascular or cerebrovascular disease. Blood flow velocities in both middle cerebral arteries (MCA) were recorded using transcranial Doppler sonography during hypercapnia, normocapnia and hypocapnia. Several psychometric tests were performed. Patients' age, disease duration and severity of dementia did not correlate with vasomotor reactivity. Exploratory analysis revealed that mean flow velocities under hypercapnia correlated with severity of dementia and with patient's age. This suggests that the disease process does not influence the autoregulative function of small resistance vessels as assessed by CO2 challenge. However, the excess reduction of the highest flow velocities measured during maximal CO2 stimulation indicates that the number of small capillaries are diminished, or alternatively that the diameters of these capillaries are reduced in Alzheimer's disease.
Antibody levels and protection after hepatitis B vaccine: results of a 22-year follow-up study and response to a booster dose.

BACKGROUND The duration of protection in children and adults (including health care workers) resulting from the hepatitis B vaccine primary series is unknown. METHODS To determine the protection afforded by hepatitis B vaccine, Alaska Native persons who had received plasma-derived hepatitis B vaccine when they were >6 months of age were tested for antibody to hepatitis B surface antigen (anti-HBs) 22 years later. Those with levels <10 mIU/mL received 1 dose of recombinant hepatitis B vaccine and were evaluated on the basis of anti-HBs measurements at 10-14 days, 30-60 days, and 1 year. RESULTS Of 493 participants, 60% (298) had an anti-HBs level >or=10 mIU/mL. A booster dose was administered to 164 persons, and 77% responded with an anti-HBs level >or=10 mIU/mL at 10-14 days, reaching 81% by 60 days. Response to a booster dose was positively correlated with younger age, peak anti-HBs response after primary vaccination, and the presence of detectable anti-HBs before boosting. Considering persons with an anti-HBs level >or=10 mIU/mL at 22 years and those who responded to the booster dose, protection was demonstrated in 87% of the participants. No new acute or chronic hepatitis B virus infections were identified. CONCLUSIONS The protection afforded by primary immunization with plasma-derived hepatitis B vaccine during childhood and adulthood lasts at least 22 years. Booster doses are not needed.
Changes in Kidney Function and in the Rate of Tubular Dysfunction After Tenofovir Withdrawal or Continuation in HIV-Infected Patients

Introduction:Longitudinal data on the changes in kidney function and tubular abnormalities in case of tenofovir disoproxil fumarate (TDF) withdrawal or continuation are scarce. Methods:Prospective study of 228 patients receiving TDF, with 3 sequential determinations of serum creatinine, estimated glomerular filtration rate (eGFR), phosphatemia, and different urinary parameters (protein, albumin, phosphaturia, uricosuria, and glycosuria). Changes were analyzed in patients who interrupted TDF as compared to those who continued the same regimen. Proximal renal tubular dysfunction (PRTD) was defined as ≥2 tubular abnormalities. Results:After a median follow-up of 59.5 months, 78 patients (34%) had PRTD, mainly proteinuria (40%) and phosphaturia (61%), and time on TDF explains the severity of tubular alterations and eGFR slopes. In 35 switching patients, there was a rapid and significant eGFR improvement (median +4.1 ml/min per 1.73 m2; P = 0.02), leading to a 39%–83% reduction in the prevalence of tubular abnormalities and of PRTD in less than 1 year (66%–39%). In comparison, 193 patients continuing the same regimen for 21.2 months had a small but significant and progressive eGFR decrease (−2.9 mL·min−1·1.73 m−2; P < 0.01), and a progressive rise in the prevalence of phosphaturia, uricosuria, and glycosuria (+9%–56%). In linear mixed-effect model, subsequent eGFR impairment was associated with proteinuria and time on TDF, and eGFR improvement with TDF discontinuation. Conclusions:Our data support the role of use and time on TDF in eGFR decline and tubular dysfunction. In contrast, TDF withdrawal is followed by a rapid and significant, although partial, recovery of eGFR and tubular abnormalities.
Hospital Costs in Patients with Nosocomial Methicillin-Resistant or Methicillin-Susceptible Staphylococcus aureus Bloodstream Infection

To the editor. —Given our interest in health economics in the field of infectious disease research, we read with interest the article by Dr Ben-David and colleagues published in the May 2009 issue of the journal. 1-5 The authors examined the attributable impact of methicillin resistance among patients with nosocomial methicillin-resistant Staphylococcus aureus bloodstream infection on hospital mortality, length of stay, and costs, compared with patients with nosocomial methicillin-susceptible S. aureus bloodstream infection. Their initial results suggested increased resource use in terms of hospital costs and length of stay associated with methicillin resistance; however, after they had accounted for potential confounders by means of a propensity score analysis, their final results did not reveal increased resource use. 3 Although we agree with the conclusion of Dr Ben-David and colleagues, we have some suggestions regarding the additional study that they propose. In their propensity score, which was assessed for each individual case patient, the authors did not include prior use of antibiotic agents (appropriateness of therapy, number of antibiotics administered, and duration of antibiotic use) and whether the patients were cared for in a long-term care facility prior to hospital admission—both variables that are associated with acquisition of antibiotic resistance. 6-8 As such, important bias may remain, because the propensity score adjusted for in their analysis may not satisfactorily correct for existing differences between patients with nosocomial bloodstream infection caused by methicillin-resistant S. aureus and patients with nosocomial bloodstream infection caused by methicillin-susceptible S. aureus. 9 In an aim to increase the generalizability of a propensity score to other settings or institutions, however, it is important to keep such a “probability model” as simple as possible, which means retaining only the most clinically relevant variables in the final analysis. In this regard, we do not completely comprehend why some characteristics that seem not to have any relationship to methicillin resistance were included (eg, presence of cirrhosis or diabetes mellitus [P p ]; see their Table 4), while other characteristics were excluded . 7 (eg, residence in a long-term care facility), even though they were statistically and clinically relevant. We would like to kindly invite Dr Ben-David and colleagues to clarify the decision process by which potential confounders were included or excluded from the final model on which the propensity score was based.
The Well‐Temperatured Biologist

Temperature provides a powerful theme for exploring environmental adaptation at all levels of biological organization, from molecular kinetics to organismal fitness to global biogeography. First, the thermodynamic properties that underlie biochemical kinetics and protein stability determine the overall thermal sensitivity of rate processes. Consequently, a single quantitative framework can assess variation in thermal sensitivity of ectotherms in terms of single amino acid substitutions, quantitative genetics, and interspecific differences. Thermodynamic considerations predict that higher optimal temperatures will result in greater maximal fitness at the optimum, a pattern seen both in interspecific comparisons and in within‐population genotypic variation. Second, the temperature‐size rule (increased developmental temperature causes decreased adult body size) is a common pattern of phenotypic plasticity in ectotherms. Mechanistic models can correctly predict the rule in some taxa, but lab and field studies show that rapid evolution can weaken or even break the rule. Third, phenotypic and evolutionary models for thermal sensitivity can be combined to explore potential fitness consequences of climate warming for terrestrial ectotherms. Recent analyses suggest that climate change will have greater negative fitness consequences for tropical than for temperate ectotherms, because many tropical species have relatively narrow thermal breadths and smaller thermal safety margins.
The foundation degree: an education framework for rehabilitation assistants?

A major feature of foundation degrees, which were introduced as a new development in February 2000, is the high proportion of work-based learning and the concept of ‘earn and learn’. Concurrent with this development was the increasing acknowledgement of the need to provide more flexible education for the NHS workforce. A key feature of the development of foundation degrees was employer involvement in the design and delivery of the programmes, which provided an ideal opportunity to develop a health-care programme that met service needs. Bradford University was successful in obtaining funding to develop a foundation degree in health and social care as part of the pilot phase. One particular pathway of this programme was aimed at meeting the needs of rehabilitation assistants. This article describes how the course meets the demands of the modernization agenda and outlines the challenges faced and future developments. Developments are focussed on short course provision for rehabilitation assistants and a cert.
Division of Comparative Physiology and Biochemistry , Society for Integrative and Comparative Biology Plasticity of Oxidative Metabolism in Variable Climates : Molecular Mechanisms

Converting food to chemical energy (ATP) that is usable by cells is a principal requirement to sustain life. The rate of ATP production has to be sufficient for housekeeping functions, such as protein synthesis and maintaining membrane potentials, as well as for growth and locomotion. Energy metabolism is temperature sensitive, and animals respond to environmental variability at different temporal levels, from within-individual to evolutionary timescales. Here we review principal molecular mechanisms that underlie control of oxidative ATP production in response to climate variability. Nuclear transcription factors and coactivators control expression of mitochondrial proteins and abundance of mitochondria. Fatty acid and phospholipid concentrations of membranes influence the activity of membrane-bound proteins as well as the passive leak of protons across the mitochondrial membrane. Passive proton leak as well as protein-mediated proton leak across the inner mitochondrial membrane determine the efficacy of ATP production but are also instrumental in endothermic heat production and as a defense against reactive oxygen species. Both transcriptional mechanisms and membrane composition interact with environmental temperature and diet, and this interaction between diet and temperature in determining mitochondrial function links the two major environmental variables that are affected by changing climates. The limits to metabolic plasticity could be set by the production of reactive oxygen species leading to cellular damage, limits to substrate availability in mitochondria, and a disproportionally large increase in proton leak over ATP production.
Effect of the neuraminidase mutation H274Y conferring resistance to oseltamivir on the replicative capacity and virulence of old and recent human influenza A(H1N1) viruses.

BACKGROUND The viral fitness of neuraminidase inhibitor (NAI)-resistant influenza viruses is believed to be impaired. Unexpectedly, an oseltamivir-resistant A(H1N1) variant containing the H274Y neuraminidase (NA) mutation recently disseminated worldwide, suggesting that the replication and virulence properties of this mutant virus were not compromised. METHODS In vitro replicative capacities were determined for old (A/WSN/33, A/Mississipi/3/01, A/New Caledonia/20/99, and A/Solomon Islands/03/06) and recent (A/Brisbane/59/2007-like) influenza A(H1N1) viruses either harboring or not harboring the H274Y NA mutation. Ferrets were infected with the A/Brisbane/59/2007-like wild-type (WT) isolate and its H274Y NA variant. RESULTS Old A(H1N1) WT viruses grew at higher titers than did the A/Brisbane/59/2007-like viruses in vitro. The H274Y mutation was associated with reduced viral plaque areas in cells infected with A/WSN/33 and A/Mississippi/3/01, whereas the 2 A/Brisbane/59/2007-like isolates showed similar plaque sizes. In ferrets, the pyrexic response induced by the A/Brisbane/59/2007-like H274Y mutant was significantly higher than that induced by the WT isolate. Nasal wash viral titers were significantly greater for the mutant isolate on day 2 after inoculation, whereas the 2 viruses showed similar titers between days 3 and 7 after inoculation. CONCLUSIONS The viral fitness of the recent A/Brisbane/59/2007-like H274Y variant is not impaired, consistent with its global dissemination. These results reinforce the need for new antiviral strategies.
Social Network Clustering and the Spread of HIV/AIDS Among Persons Who Inject Drugs in 2 Cities in the Philippines

Introduction: The Philippines has seen rapid increases in HIV prevalence among people who inject drugs. We study 2 neighboring cities where a linked HIV epidemic differed in timing of onset and levels of prevalence. In Cebu, prevalence rose rapidly from below 1% to 54% between 2009 and 2011 and remained high through 2013. In nearby Mandaue, HIV remained below 4% through 2011 then rose rapidly to 38% by 2013. Objectives: We hypothesize that infection prevalence differences in these cities may owe to aspects of social network structure, specifically levels of network clustering. Building on previous research, we hypothesize that higher levels of network clustering are associated with greater epidemic potential. Methods: Data were collected with respondent-driven sampling among men who inject drugs in Cebu and Mandaue in 2013. We first examine sample composition using estimators for population means. We then apply new estimators of network clustering in respondent-driven sampling data to examine associations with HIV prevalence. Results: Samples in both cities were comparable in composition by age, education, and injection locations. Dyadic needle-sharing levels were also similar between the 2 cities, but network clustering in the needle-sharing network differed dramatically. We found higher clustering in Cebu than Mandaue, consistent with expectations that higher clustering is associated with faster epidemic spread. Conclusions: This article is the first to apply estimators of network clustering to empirical respondent-driven samples, and it offers suggestive evidence that researchers should pay greater attention to network structure's role in HIV transmission dynamics.
Objectively-measured physical activity of children in the Gateshead Millennium Study

Level of habitual physical activity might be an important determinant of fatness in UK children. The Gateshead Millennium study is a birth cohort of 1029 children in north-east England born between June 1999 and May 2000. Between October 2006 and December 2007 the children were involved in a follow-up study looking at various measures of physical activity, growth and nutrition. Physical activity was measured objectively in the cohort using Actigraph GT1M accelerometers (Actigraph LLC, Pensacola, FL, USA) worn on an elastic belt around their waist. The children were asked to wear the accelerometer during waking hours for 7 d, excluding water-based activities. Parents were asked to record in a simple diary the times when the belt was worn. Information from the accelerometer was analysed to ascertain time spent in moderate-vigorous physical activity (MVPA) using published cut-offs. Of 606 accelerometers given out, eighteen were lost, twenty-five were not worn, thirty-one were returned without diaries, one child was ill throughout and ten suffered a software malfunction, leaving 521. Of the 521, nine were worn for <3 d and excluded from the analysis leaving 512 (84%; 260 boys and 252 girls). The accelerometers were worn for an average of 10.8 h/d and for 6 d. The median time spent daily in MVPA was 26 (interquartile range (IQR) 18–37) min and children spent an average of 3.9 (IQR 2.6–5.8) % of their time in MVPA. Boys took part in more MVPA (28 (IQR 19–41) min/d) than girls (25 (IQR 16–35) min/d; P = 0.004) and consequently spent a greater percentage of their time in MVPA (4.2 v. 3.8; P= 0.007). Only twenty-six of 260 boys (10%) and eight of 252 girls (3%) averaged >60 min/d spent in MVPA (Figure). There was a distinct effect (P<0.001) of season on the amount of daily MVPA, with spring and summer recording more than autumn and winter (30 min v. 21 min). The most activity was recorded in June (32 min/d), closely followed by July (31 min/d), and the least in January (19 min/d). It was found that the majority (93%) of children in the study do not currently meet the health recommendation of 60 min spent in MVPA daily, even during the summer holidays (August), and this factor is likely to increase their risk of excessive fatness. Developing strategies to increase physical activity in children of this age-group should be a public health priority.
Formulation and in vitro & in vivo evaluation of a new osteoprotegerin-chitosan gel for bone tissue regeneration

The osteoprotegerin (OPG) system plays a critical role in bone remodelling by regulating osteoclast formation and activity. The study aimed to determine the physicochemical properties and biocompatibility of a newly formulated OPG-chitosan gel. The OPG-chitosan gel was formulated using human OPG protein and water-soluble chitosan. The physicochemical properties were determined using Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1002/jbm.a. 35919 This article is protected by copyright. All rights reserved. 2 Gel morphology was determined using scanning electron microscopy (SEM) and then it was subjected to a protein release assay and biodegradability test. An in vitro cytotoxicity test on normal human periodontal ligament (NHPL) fibroblasts and normal human (NH) osteoblasts was carried out using the alamarBlue assay. In vivo evaluation in a rabbit model involved creating critical-sized defects in calvarial bone, filling with the OPG-chitosan gel and sacrificing at 12 weeks. In vitro results demonstrated that the 25 kDa OPG-chitosan gel had the highest rate of protein release and achieved 90% degradation in 28 days. At 12 weeks, the defects filled with 25 kDa OPG-chitosan gel showed significant (p < 0.05) new bone formation and the highest expression of osteocalcin and osteopontin compared to controls. Thus, the 25 kDa OPG-chitosan gel could be a promising new biomaterial for tissue engineering.