Miracle-dz/UniFAR-FTUs huggingface dataset:
Animal models of age-related macular degeneration and their translatability into the clinic

Age-related macular degeneration (AMD) is a leading cause of blindness in people over the age of 55. Despite its common nature, the etiology of the disease involves both genetic and environmental factors, the interaction of which is not fully understood. Animal models, including the mouse, rat, rabbit, pig and non-human primate, have been developed to study various aspects of the disease and to evaluate novel therapies; however, no single model has been developed to emulate all aspects of the disease. This review will discuss the various existing models of AMD, their strengths and limitations and examples of their use in current AMD research.
Phase 2 study of BACOPP (bleomycin, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) in older patients with Hodgkin lymphoma: a report from the German Hodgkin Study Group (GHSG).

For older patients with early unfavorable or advanced stage Hodgkin lymphoma (HL) the prognosis is much worse than for younger HL patients. We thus developed a new regimen, BACOPP (bleomycin, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone), to improve both tolerability and efficacy of treatment for older HL patients. Between 2004 and 2005, 65 patients with early unfavorable or advanced stage HL aged between 60 and 75 years were enrolled in this phase 2 trial. Treatment consisted of 6 to 8 cycles of BACOPP. Residual tumor masses were irradiated. Primary endpoints were feasibility as determined by adherence to protocol and overall response rate. Secondary endpoints included toxicity, freedom from treatment failure, and progression free and overall survival. For the final analysis 60 patients (92%) were eligible; 75% of treatment courses were administered according to protocol. World Health Organization grade 3/4 toxicities occurred in 52 patients. Fifty-one patients (85%) achieved complete remission, 2 (3%) partial remission, and 4 (7%) developed progressive disease. With a median observation time of 33 months, 18 patients died (30%), including 7 treatment-associated deaths. Three patients died before response assessment. Thus, the BACOPP regimen is active in older HL patients but is compromised by a high rate of toxic deaths. This trial was registered at www.clinicaltrials. gov as #NCT00284271.
V. Meta-Analysis of the Efficacy of Hormone Replacement Therapy in Treating and Preventing Osteoporosis in Postmenopausal Women

Objective: To review the effect of hormone replacement therapy (HRT) on bone density and fractures in postmenopausal women. Data Source: We searched MEDLINE and EMBASE from 1966 to 1999, the Cochrane Controlled Register, citations of relevant articles, and proceedings of international meetings for eligible randomized controlled trials. We contacted osteoporosis investigators to identify additional studies, and primary authors for unpublished data. Study Selection: We included 57 studies that randomized postmenopausal women to HRT or a control (placebo or calcium/vitamin D) and were of at least 1 yr in duration. Seven of these studies reported fractures. Data Abstraction: For each study, three independent reviewers assessed the methodological quality and abstracted the data. Data Synthesis: HRT showed a trend toward reduced incidence of vertebral fractures [relative risk (RR) 0.66, 95% confidence interval (CI) 0.41-1.07; 5 trials] and nonvertebral fractures (RR 0.87, 95% CI 0.71-1.08; 6 trials). HRT had a consistent effect on bone mineral density (BMD) at all sites. The difference between HRT and control in the percent change in bone density at 2 yr was 6.76 (5.83, 7.89; 21 trials) at the lumbar spine and 4.53 (3.68, 5.36; 14 trials) and 4.12 (3.45, 4.80; 9 trials) at the forearm and femoral neck, respectively. Conclusions: HRT has a consistent, favorable and large effect on bone density at all sites. The data show a nonsignificant trend toward a reduced incidence in vertebral and nonvertebral fractures.
Diagnosis and Treatment of Lesions of the Upper Airway: Part I: The Neonate

The upper airway of the newborn infant demonstrates much more fragility in its predisposition to develop obstruction in comparison to older children and adults. Multiple reasons account for this, including specific anatomic differences, increased flaccidity of the cartilagenous framework, incomplete neurologic development, and increased susceptibility to respiratory pathogens. When dealing with patients in the neonatal intensive care unit (NICU) setting, other significant factors contribute to upper airway pathologic conditions, including premature gestational age, endotracheal intubation, mechanical ventilation, and associated congenital anomalies. In the neonatal age group, congenital etiologies for airway obstruction are more common than in older children in whom acquired causes account for a higher proportion of the airway pathologic states. The management of infants with upper airway disease requires a team approach with close communication between the pediatric otolaryngologist, neonatologist, anesthesiologist, and radiologist. With a well-planned, systemic approach to the diagnosis and management of these patients, the majority of these cases should attain a successful outcome.
Endothelin receptors in augmented vasoconstrictor responses to endothelin‐1 in chronic intermittent hypoxia

Chronic intermittent hypoxia (CIH) contributes to the development of cardiovascular diseases in patients with obstructive sleep apnoea. Many studies have shown an association between increased circulating endothelin (ET)‐1 levels and CIH. The aim of the present study was to determine the role of ET receptors in altered aortic function in an animal model of CIH. Rats were subjected to CIH (Fio2 9% for 1 min, repeated every 2 min for 8 h/day, 7 days/week) for 3 weeks. After 3 weeks, the rats were killed and their aortas retrieved for use in in vitro experiments (isometric force measurement), histological analysis, immunohistochemistry and western blotting. Aortas from rats subjected to CIH exhibited marked endothelial dysfunction and increased responsiveness to ET‐1. Furthermore, CIH induced increased ET‐1 and ETA receptor expression, whereas ETB receptor expression was decreased. Aortic contractile responses to ET‐1 were inhibited by the ETA and ETB receptor antagonists BQ‐123 and BQ‐788, respectively. Acetylcholine‐induced relaxation responses were significantly attenuated in aortas from rats subjected to CIH, whereas CIH had no significant effect on aortic responses to sodium nitroprusside. The results of the present study suggest that increased expression of ETA receptors, which mediate a potent vasoconstrictor response, plays an important role in the pathogenesis of CIH. In addition, decreased endothelial ETB receptor expression, which is associated with the functional decline of endothelium‐dependent vasodilation, also contributes to the pathogenesis of CIH. It appears that the ETB receptor‐induced buffering of ET‐1 responsiveness is mediated via a nitric oxide‐dependent mechanism.
Recent progress in gastric arrhythmia: Pathophysiology, clinical significance and future horizons

Gastric arrhythmia continues to be of uncertain diagnostic and therapeutic significance. However, recent progress has been substantial, with technical advances, theoretical insights and experimental discoveries offering new translational opportunities. The discoveries that interstitial cells of Cajal (ICC) generate slow waves and that ICC defects are associated with dysmotility have reinvigorated gastric arrhythmia research. Increasing evidence now suggests that ICC depletion and damage, network disruption and channelopathies may lead to aberrant slow wave initiation and conduction. Histological and high‐resolution (HR) electrical mapping studies have now redefined the human ‘gastric conduction system’, providing an improved baseline for arrhythmia research. The application of HR mapping to arrhythmia has also generated important new insights into the spatiotemporal dynamics of arrhythmia onset and maintenance, resulting in the emergence of new provisional classification schemes. Meanwhile, the strong associations between gastric functional disorders and electrogastrography (EGG) abnormalities (e.g. in gastroparesis, unexplained nausea and vomiting and functional dyspepsia) continue to motivate deeper inquiries into the nature and causes of gastrointestinal arrhythmias. In future, technical progress in EGG methods, new HR mapping devices and software, wireless slow wave acquisition systems and improved gastric pacing devices may achieve validated applications in clinical practice. Neurohormonal factors in arrhythmogenesis also continue to be elucidated and a deepening understanding of these mechanisms may open opportunities for drug design for treating arrhythmias. However, for all translational goals, it remains to be seen whether arrhythmia can be corrected in a way that meaningfully improves organ function and symptoms in patients.
Targeting transgene to the heart and liver with AAV9 by different promoters

Adeno‐associated virus (AAV) has become one of the most promising gene transfer tools for gene therapy. This work aims to evaluate tropism, gene transfer efficiency and safety of AAV9 vectors produced with recombinant baculovirus (rBac)‐based system. AAV9‐CMV‐GFP and AAV9‐CBA‐GFP were produced using a rBac system, 1 × 1011 particles of each vectors were administered intravenously (i.v.) into mice and animals were killed at 1, 2, 3, 4, 5 and 8 weeks after administration. The GFP expression in different organs was analyzed by fluorescence imaging and Western blot. Viral genomic quantities were measured using qPCR. In vitro transduction efficiency of AAV9 vectors in primary cardiomyocytes and hepatocytes was determined by flow cytometry. Toxicity of AAV9 vectors was evaluated by determining certain cardiac and liver injury biomarkers and renal function test in vivo and TUNEL analysis in vitro. The data showed that AAV9 viral particles packaged by the rBac system were fully functional in vivo and in vitro. The CMV promoter predominantly induced higher cardiac GFP transgene expression and DNA copy numbers while the CBA promoter resulted in robust GFP expression and high vector DNA copy numbers in mouse liver, both in a time‐dependent increased manner. Such distinct preferential effects were also observed in the heart and liver as early as 3 and 5 days after co‐infection. Both the AAV9‐CMV and AAV9‐CBA viral packages did not induce heart, liver and renal damage and cell apoptosis. These results indicated that AAV9‐CMV can efficiently and safely direct cardiac gene transfer, whereas AAV9‐CBA is preferential for liver gene delivery.
Rates of depression in elderly volunteers with isolated systolic hypertension

In a multicentre pilot study of the treatment of 551 elderly patients with isolated systolic hypertension (SHEP), the effects on behavioural dimensions were also investigated. The presence and severity of depression, dementia and disability was measured by the SHORT‐CARE at baseline, annual follow up and, in a random half of subjects at bimonthly intervals. Remarkably low rates and levels of depression were noted in comparison with community norms; neither demographic characteristics, rates of dementia nor medication effects explained this finding. However, controlling for disability largely resolved the discrepancy in depression rates between SHEP and the community norms.
ARTIFICIAL TEAR SOLUTIONS AND PROTECTION OF THE CORNEAL EPITHELIUM FROM DESICCATION

Desiccation of the ocular surface in dry environments is one of the factors contributing to discomfort in dry eye patients. An in vivo desiccation model was used to test efficacy of artificial tear products for prevention of ocular surface damage during extended desiccating exposure. One drop of an artificial tear or a lens rewetting solution was placed on the eye of an anesthetized rabbit and the eye was held open with a speculum for 2 hr. Desiccated eyes were held open for 2 hr without application of a tear solution. Eyes were stained with 1% methylene blue in BSS. Naïve control eyes were stained with methylene blue without prior desiccation. The percentage of corneal area stained was scored and a 8-mm button of central cornea was extracted in acetone:saturated sodium sulfate (7:3). Absorbance of extracts was measured at 660 nm. Extract analysis showed that four of the five tear products tested offered complete protection from desiccation (not different from naïve control), while one solution, which was hypotonic, offered partial protection (uptake different from desiccated and naïve corneas). The lens rewetting solution, which contains EDTA, did not protect the cornea from desiccation. This in vivo model is useful in evaluating artificial tear solutions for their ability to protect the corneal epithelium from damage during prolonged desiccating exposure. This method can be used to test toxicity of tear solution components, for preclinical evaluation of new tear formulas and may be useful for prediction of product efficacy in clinical use.
The dynamic evolution of Drosophila innubila Nudivirus

Viruses coevolve with their hosts to overcome host resistance and gain the upper hand in the evolutionary arms race. Drosophila innubila nudivirus (DiNV) is a double stranded DNA virus, closely related to Oryctes rhinoceros nudivirus (OrNV) and Kallithea virus. DiNV is the first DNA virus found to naturally infect Drosophila and therefore has the potential to be developed as a model for DNA virus immune defense and host/virus coevolution within its well-studied host system. Here we sequence and annotate the genome of DiNV and identify signatures of adaptation, revealing clues for genes involved in host-parasite coevolution. The genome is 155555bp long and contains 107 coding open reading frames (ORFs) and a wealth of AT-rich simple sequence repeats. While synteny is highly conserved between DiNV and Kallithea virus, it drops off rapidly as sequences become more divergent, consistent with rampant rearrangements across nudiviruses. Overall, we show that evolution of DiNV is likely due to adaptation of few genes coupled with high gene turnover. Highlights We sequence the genome of DiNV. Few genes are rapidly evolving between nudiviruses. We find high gene turnover between DiNV and its closest relatives. Helicase and ODV-E56 show consistent signatures of adaptation. Abbreviations DiNV Drosophila innubila Nudivirus OrNV Oryctes rhinoceros Nudivirus AcMNPV Autographa californica Multiple Nucleopolyhedrovirus ORF Open reading frame ODV-E56 Occulsion derived virus envelope protein 56 SNP Single nucleotide polymorphism
Synchronous papillary urothelial carcinoma of urinary bladder and adenocarcinoma of stomach in a middle-aged man: An extremely rare association with therapeutic dilemma

Synchronous occurrence of urinary bladder carcinoma and gastric carcinoma is very rare. A middle-aged Asian man presented with complaints of hematuria which was diagnosed due to muscle invasive papillary urothelial carcinoma of urinary bladder. Metastatic work-up revealed simultaneous presence of locally advanced gastric adenocarcinoma. He was treated with TURBT for the bladder cancer and was planned for radical gastric resection followed by radiation to urinary bladder and stomach with concurrent chemotherapy. However, due to very advanced nature of the gastric tumor patient was treated only with palliative gastric resection followed by palliative radiation to both urinary bladder and stomach due to his poor performance status. Lack of published English literature and evidence related to such clinical entity made this an extremely rare clinical entity and treatment decision difficult.
Recent developments in vitamin D deficiency and muscle weakness among elderly people

Elderly people's liability to falls and fractures is increased by many factors, including visual impairment, neurological disorders, orthopaedic disabilities, and drug effects. In one study showing that more than a third of people aged over 65 fell each year, the main risk factor was muscle weakness.1 Poor muscle strength and weakness may be associated with vitamin D deficiency, which is common among elderly people2 because the capacity of the skin to synthesise the provitamin calcidiol (25-hydroxycholecalciferol) decreases with age. Serious deficiency of vitamin D is common among elderly housebound people in old people's homes, nursing homes, and long stay wards and has been identified as an important public health problem.2–5 In this review I discuss recent developments in screening and treating vitamin D deficiency among elderly housebound people aimed at reducing the incidence of falls and fractures. This review is based on material identified through Medline searches and the author's personal library, and through discussions with researchers. Higher plasma concentrations of calcidiol are associated with muscle strength, physical activity, and ability to climb stairs and lower concentrations with falls among elderly people.6 7 Indeed, in a randomised controlled trial elderly women given 800 IU vitamin D daily with calcium had a 47% reduction in falls and fractures compared with controls receiving calcium alone over 12 months.8 In another trial with three month follow up, the incidence of falls was almost halved and musculoskeletal function improved among elderly people who had 800 IU vitamin D with calcium compared with calcium alone.9 The prevalence of falls at age 85 is double that at ages 65-75.10 Most studies of osteoporosis among elderly people cover a wide age range and do not focus specifically on those who are housebound, despite the fact that age and …
Observations and simulations of the ERS wind scatterometer response over a Sahelian region

ERS-1 wind-scatterometer data acquired over a saharo-sahelian region located in the Gourma (Mali) during the period 1992-1995, are analysed. Experimental observations show that /spl sigma//spl deg/(45/spl deg/) temporal data display a marked seasonality associated with the development and senescence of annual grasses during the rainy seasons. The interpretation of the temporal /spl sigma//spl deg/ plots is performed with the assistance of a semi-empirical backscattering model combined with an ecosystem grassland model. The use of this model allows the total biomass to be estimated with a 33% error.
Coverage and uptake of systematic postal screening for genital Chlamydia trachomatis and prevalence of infection in the United Kingdom general population: cross sectional study

Abstract Objective To measure the coverage and uptake of systematic postal screening for genital Chlamydia trachomatis and the prevalence of infection in the general population in the United Kingdom. To investigate factors associated with these measures. Design Cross sectional survey of people randomly selected from general practice registers. Invitation to provide a specimen collected at home. Setting England. Participants 19 773 men and women aged 16-39 years invited to participate in screening. Main outcome measures Coverage and uptake of screening; prevalence of chlamydia. Results Coverage of chlamydia screening was 73% and was lower in areas with a higher proportion of non-white residents. Uptake in 16-24 year olds was 31.5% and was lower in men, younger adults, and practices in disadvantaged areas. Overall prevalence of chlamydia was 2.8% (95%confidence interval 2.2% to 3.4%) in men and 3.6% (3.1% to 4.9%) in women, but it was higher in people younger than 25 years (men 5.1%; 4.0% to 6.3%; women 6.2%; 5.2% to 7.8%). Prevalence was higher in the subgroup of younger women who were harder to engage in screening. The strongest determinant of chlamydial infection was having one or more new sexual partners in the past year. Conclusions Postal chlamydia screening was feasible, but coverage was incomplete and uptake was modest. Lower coverage of postal screening in areas with more non-white residents along with poorer uptake in more deprived areas and among women at higher risk of infection could mean that screening leads to wider inequalities in sexual health.
Fallout: An American Nuclear Tragedy

More and more often, a judge is called upon to make decisions that should be made by the legislative or executive branches of government after consultation with scientists and other experts. This book is the story of a court case in Salt Lake City, Utah, that, on May 10, 1984, resulted in an award of $2.66 million in damages to eight persons with leukemia, one with thyroid cancer, and another with breast cancer. The cancers were judged to have been caused by the radioactive fallout from the atmospheric tests of nuclear weapons in southern Nevada during the 1950s and early 1960s. The judge ruled that the Atomic Energy Commission (AEC) had failed to warn the downwind citizens of the dangers from fallout so that they could take simple precautionary measures, such as staying indoors during the tests. The initial decision was reversed subsequently by the Court of Appeals on the
Effects of nitric oxide on large‐conductance Ca2+‐activated K+ currents in human cardiac fibroblasts through PKA and PKG‐related pathways

The human cardiac fibroblast (HCF) is the most abundant cell type in the myocardium, and HCFs play critical roles in maintaining normal cardiac function. However, unlike cardiomyocytes, the electrophysiology of HCFs is not well established. In the cardiovascular system, Ca2+‐activated K+ (KCa) channels have distinct physiological and pathological functions, and nitric oxide (NO) plays a key role. In this study, we investigated the potential effects of NO on KCa channels in HCFs. We recorded strong oscillating, well‐maintained outward K+ currents without marked inactivation throughout the test pulse period and detected outward rectification in the I‐V curve; these are all characteristics that are typical of KCa currents. These currents were blocked with iberiotoxin (IBTX, a BKCa blocker) but not with TRAM‐34 (an IKCa blocker). The amplitudes of the currents were increased with SNAP (an NO donor), and these increases were inhibited with IBTX. The SNAP‐stimulating effect on the BKCa currents was blocked by pretreatment with KT5823 (a protein kinase G [PKG] inhibitor) or 1 H‐[1,‐2, ‐4] oxadiazolo‐[4,‐3‐a] quinoxalin‐1‐one (ODQ; a soluble guanylate cyclase inhibitor). Additionally, 8‐bromo‐cyclic guanosine 3’,5’‐monophosphate (8‐Br‐cGMP) stimulated the BKCa currents, and pretreatment with KT5720 (a protein kinase A [PKA] inhibitor) and SQ22536 (an adenylyl cyclase inhibitor) blocked the NO‐stimulating effect on the BKCa currents. Furthermore, 8‐bromo‐cyclic adenosine 3’,5’‐monophosphate (8‐Br‐cAMP) activated the BKCa currents. These data suggest that BKCa current is the main subtype of the KCa current in HCFs and that NO enhances these currents through the PKG and PKA pathways.