Miracle-dz/UniFAR-FTUs huggingface dataset:
The drusenlike phenotype in aging Ccl2-knockout mice is caused by an accelerated accumulation of swollen autofluorescent subretinal macrophages.

PURPOSE Drusen, which are defined clinically as yellowish white spots in the outer retina, are cardinal features of age-related macular degeneration (AMD). Ccl2-knockout (Ccl2(-/-)) mice have been reported to develop drusen and phenotypic features similar to AMD, including an increased susceptibility to choroidal neovascularization (CNV). This study was conducted to investigate the nature of the drusenlike lesions in vivo and further evaluate the Ccl2(-/-) mouse as a model of AMD. METHODS The eyes of 2- to 25-month-old Ccl2(-/-) and C57Bl/6 mice were examined in vivo by autofluorescence scanning laser ophthalmoscopy (AF-SLO) and electroretinography, and the extent of laser-induced CNV was measured by fluorescein fundus angiography. The retinal morphology was also assessed by immunohistochemistry and quantitative histologic and ultrastructural morphometry. RESULTS The drusenlike lesions of Ccl2(-/-) mice comprised accelerated accumulation of swollen CD68(+), F4/80(+) macrophages in the subretinal space that were apparent as autofluorescent foci on AF-SLO. These macrophages contained pigment granules and phagosomes with outer segment and lipofuscin inclusions that may account for their autofluorescence. Only age-related retinal pigment epithelium (RPE) damage, photoreceptor loss, and sub-RPE deposits were observed but, despite the accelerated accumulation of macrophages, we identified no spontaneous development of CNV in the senescent mice and found a reduced susceptibility to laser-induced CNV in the Ccl2(-/-) mice. CONCLUSIONS These findings suggest that the lack of Ccl2 leads to a monocyte/macrophage-trafficking defect during aging and to an impaired recruitment of these cells to sites of laser injury. Other, previously described features of Ccl2(-/-) mice that are similar to AMD may be the result of aging alone.
Two Steady‐Entrainment Phases and Graded Masking Effects by Light Generate Different Circadian Chronotypes in Octodon degus

Processes involved in the operation of the circadian pacemaker are well characterized; however; little is known about what mechanisms drive the overt diurnal, nocturnal, or crepuscular behavior in a species. In this context, dual‐phasing rodents, such as Octodon degus, emerge as a useful model to decipher these keys. Two main chronotypes, nocturnal and diurnal, have been traditionally described in laboratory‐housed degus based on the percentage of activity displayed by the animals during the scotophase or photophase. However, if one considers also the entrainment phase angle during the first days following a change from LD to DD conditions, a third chronotype (intermediate)—or more properly, a continuous grading of circadian expressions between diurnal and nocturnal chronotype—can be observed. Our experiments suggest the pacemaker of the diurnal animal is entrained to the photophase, and light does not exert a negative masking effect. The pacemaker of the nocturnal degus, on the other hand, is entrained to the scotophase, and light exerts a strong negative masking effect. Finally, the intermediate chronotype is characterized by variable negative masking effect of light overlapping a pacemaker entrained to the photophase. The phase shift inversion from diurnal to nocturnal chronotype is related to the availability of a wheel in the cage, and the effect may be located downstream from the clock. However, body temperature rhythm recordings, less affected by masking effects, point to an involvement of the circadian pacemaker in chronotype differentiation, as transient entrainment cycles, and not an abrupt phase shift, were detected after providing access to the wheel. The diurnality of degus seems to be the result of a variety of mechanisms, which may explain how different processes can lead to similar chronotypes.
Corporate Political Activism and Audit Fees: Evidence from Initial Public Offerings

Although active political strategies may lead to lucrative benefits, they are often associated with non-transparent diverting practices. Using a hand-collected data set of politically connected U.S. IPOs, we investigate how auditors respond to corporate political activism. We find that auditors charge higher audit fees to politically connected firms than to non-connected ones, suggesting that agency costs dominate the strategic benefits of political affiliations. This relationship is especially pronounced among firms for which are risky, operationally complex, or with reputable audit committees. In addition, we reveal that auditors consider political ideology as a useful proxy for managements’ philosophy and operating style when assessing their clients’ audit risk. Taken together, our evidence indicates that auditors incorporate the interplay between politics and corporations into the pricing of their auditing services.
The treatment of HCV in patients with haemoglobinopathy in Kurdistan Region, Iraq: a single centre experience

SUMMARY Various variables that might influence the rapid and sustained virological response to recombinant PEG-IFN-α-2a were explored in Iraqi HCV-infected patients with haemoglobinopathy. Forty-three patients were evaluated for the relationship between rapid virological response (RVR), IL-28B polymorphism, viral load, liver enzyme levels, blood group, ultrasound findings, or HCV genotype and the sustained virological response (SVR) achievement. The overall RVR was 55·81% while the overall SVR was 53·49%. SVR in patients that achieved RVR was 82·61% (P = 0·0004). A significant association was found between initial alanine transaminase levels and viral load with SVR achievement (P = 0·025) and (P = 0·004), respectively. Thirty-two (74%) out of 43 of our samples were host genotyped at the IL-28B locus as CC, a significant association was found between CC group and SVR achievement (P = 0·04). Of our samples, 23/43 (53%) were typed as HCV genotype 4, 10/43 (23%) as genotype 1, 9/43 (20·9%) as genotype 3 and 1/43 (2·3%) as genotype 2. A significant association was found between genotype 3 and SVR achievement (P = 0·006). Multivariate analysis showed that only RVR achievement independently associated with SVR in the Iraqi population (P = 0·00). These results can be used to classify the patients requiring the more expensive new direct-acting antiviral drugs.
Complex Subunit Assembly of Neuronal Voltage-gated K+Channels

Neurons require specific patterns of K+ channel subunit expression as well as the precise coassembly of channel subunits into heterotetrameric structures for proper integration and transmission of electrical signals. In vivo subunit coassembly was investigated by studying the pharmacological profile, distribution, and subunit composition of voltage-gated Shaker family K+(Kv1) channels in rat cerebellum that are labeled by125I-margatoxin (125I-MgTX;K d , 0.08 pm). High-resolution receptor autoradiography showed spatial receptor expression mainly in basket cell terminals (52% of all cerebellar sites) and the molecular layer (39% of sites). Sequence-directed antibodies indicated overlapping expression of Kv1.1 and Kv1.2 in basket cell terminals, whereas the molecular layer expressed Kv1.1, Kv1.2, Kv1.3, and Kv1.6 proteins. Immunoprecipitation experiments revealed that all 125I-MgTX receptors contain at least one Kv1.2 subunit and that 83% of these receptors are heterotetramers of Kv1.1 and Kv1.2 subunits. Moreover, 33% of these Kv1.1/Kv1.2-containing receptors possess either an additional Kv1.3 or Kv1.6 subunit. Only a minority of the 125I-MgTX receptors (<20%) seem to be homotetrameric Kv1.2 channels. Heterologous coexpression of Kv1.1 and Kv1.2 subunits in COS-1 cells leads to the formation of a complex that combines the pharmacological profile of both parent subunits, reconstituting the native MgTX receptor phenotype. Subunit assembly provides the structural basis for toxin binding pharmacology and can lead to the association of as many as three distinct channel subunits to form functional K+channels in vivo.
Large electrodes improve nerve conduction repeatability in controls as well as in patients with diabetic neuropathy

Recording site is an important cause of variability of compound muscle action potential (CMAP) and conduction parameters, which can be reduced by using large electrodes. Repeatability of CMAP and conduction parameters of conventional and large electrodes was compared in 16 controls and 17 diabetic neuropathic patients, using defined recording sites linked to anatomical landmarks. Right‐sided median, peroneal, and tibial nerves were investigated twice by the same examiner, with a 1–2 week interval. Compared to previous studies, conventional electrodes on strictly defined recording sites resulted in better repeatability: intraindividual coefficients of variation (CV) varied between 4% and 14.4% for all parameters. CV of conduction parameters, not published previously, was smaller than CV of CMAP parameters. The use of large electrodes improved repeatability further: large electrodes resulted in substantially smaller CV for duration, amplitude, area, and changes of amplitude and area over a length of nerve, which were reduced by 10%, 31%, 29%, 27%, and 16%, respectively. Patients had higher CV than controls; large electrodes reduced patient CV more than control CV, resulting in less contrast between groups. Strictly defined recording sites and large electrodes improve repeatability of motor conduction studies to relevant degrees: all CMAP and conduction parameters are suitable for longitudinal studies of neuropathic patients. © 1996 John Wiley & Sons, Inc.
Impact of lymphovascular invasion on oncological outcomes in patients with upper tract urothelial carcinoma after radical nephroureterectomy

To assess the impact of lymphovascular invasion (LVI) on upper urinary tract urothelial carcinomas (UTUCs) in a multicentre study on cancer‐specific survival (CSS), recurrence‐free survival and metastasis‐free survival (MFS). To show the negative impact of LVI for patients with pN0/x disease and to stratify these patients into risk groups for metastatic relapse.
Manipulation of profits in Italian publicly-funded healthcare trusts

ABSTRACT This paper examines earnings management in state-funded Italian healthcare trusts. Italy is unique in requiring trusts to have balanced budgets by law. Small negative and positive deviations from a balanced budget had quite different consequences. The authors found no evidence of accounting manipulation when trusts posted small losses. However, trusts were found to manipulate discretionary accruals, provisions and non-operating expenses to reduce small positive deviations from zero-profit. IMPACT The authors have highlighted unintended consequences resulting from a balanced budget regime that are important for policy-makers making changes to financial reporting requirements. Policy-makers interested in mandating a ‘balanced budget’ in any sector that offers public services should be aware of potential manipulation of reports both through accruals and, importantly, through cuts in expenses, which may ultimately affect the level and quality of the services provided.
Inferior Parietal Lobule Volume and Schneiderian First-Rank Symptoms in Antipsychotic-Naïve Schizophrenia: A 3-Tesla MRI Study

Background: As per Frith's neuro-cognitive model, inferior parietal lobule (IPL) is implicated in the pathogenesis of Schneiderian first-rank symptoms (FRS) in schizophrenia. The specific role of IPL structural abnormalities in the pathogenesis of FRS is yet to be ascertained. Materials and Methods: Using 3-tesla MRI scanner, this first-time study examined antipsychotic-naïve schizophrenia patients ( n = 28) (patients with FRS [FRS +]: N = 14, M: F = 7:7; and patients without FRS [FRS-]: N = 14, M: F = 7:7) in comparison with sex-, handedness-, education- and socioeconomic status-matched healthy controls (n = 14, M: F = 7:7). The volume of IPL was measured using a three-dimensional, interactive, semi-automated analysis, with good inter-rater reliability. Results: FRS + patients showed significant volume deficit in right IPL in comparison with healthy controls (F = 4.0; P=.028) after controlling for the potential confounding effects of age, sex and intracranial volume. Conclusions: Right IPL volume deficit in FRS+patients adds further support to the Frith's model of FRS in schizophrenia.
Predictive factors of work disability in rheumatoid arthritis: a systematic literature review

Background: Work disability—a common outcome of rheumatoid arthritis (RA)—is a societal (for example, financial costs) and individual problem (for example, loss of status, income, social support, and distraction from pain and distress). Until now, factors that predict work disability in RA have not been systematically reviewed. Objective: To determine predictive factors of work disability in RA as reported in the literature. Methods: A systematic literature search in Cinahl (1988–2004), Embase (1988–2004), and Medline (1989–2004) was followed by the application of two sets of criteria related to: (a) methodological quality, and (b) measurement of the predictive factor. Based on the quality and the consistency of the findings, a rating system was used to assess the level of evidence for each predictive factor. Results: Nineteen publications (17 cohorts) were identified, of which 13 met the general methodological quality criteria. Results provided strong evidence that physical job demands, low functional capacity, old age, and low education predict work disability in RA. Remarkably, biomedical variables did not consistently predict work disability. Moreover, owing to the lack of high quality studies no evidence was found for personal factors such as coping style, and work environmental factors such as work autonomy, support, work adjustments that are presumed crucial in the work disablement process. Conclusions: The results indicate that work disability in RA is a biopsychosocially determined misfit between individual capability and work demands.
Glial Cell Line-Derived Neurotrophic Factor Partially Ameliorates Motor Symptoms without Slowing Neurodegeneration in Mice with Respiratory Chain-Deficient Dopamine Neurons

Degeneration of midbrain dopamine neurons causes the striatal dopamine deficiency responsible for the hallmark motor symptoms of Parkinson's disease (PD). Intraparenchymal delivery of neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF), is a possible future therapeutic approach. In animal PD models, GDNF can both ameliorate neurodegeneration and promote recovery of the dopamine system following a toxic insult. However, clinical studies have generated mixed results, and GDNF has not been efficacious in genetic animal models based on α-synuclein overexpression. We have tested the response to GDNF in a genetic mouse PD model with progressive degeneration of dopamine neurons caused by mitochondrial impairment. We find that GDNF, delivered to the striatum by either an adeno-associated virus or via miniosmotic pumps, partially alleviates the progressive motor symptoms without modifying the rate of neurodegeneration. These behavioral changes are accompanied by increased levels of dopamine in the midbrain, but not in striatum. At high levels, GDNF may instead reduce striatal dopamine levels. These results demonstrate the therapeutic potential of GDNF in a progressively impaired dopamine system.
Associative Agreement as a Predictor of Naming Ability in Alzheimer's Disease: A Case for the Semantic Nature of Associative Links

We aimed to address the long-standing issue of the nature of the relationships that link a cue word to words associated with it. In keeping with a recently proposed neuropsychological model of semantic memory (Zannino et al., 2015), we provide support for the hypothesis that associative links are semantic in nature and not lexical. In support of this hypothesis, we demonstrate a relationship in healthy subjects between the probability of producing word X in response to cue word Y in a free association task and the probability of using word X to describe the meaning of word Y. Furthermore, we provide evidence that associative measures are altered in people suffering from Alzheimer's disease (AD) and predict their level of performance in a picture-naming task. We provide a parsimonious account of the experimental data gathered form these different sources of evidence according to the hypothesis that the links between a cue word and its associates can be viewed as binding a concept (the cue) to pieces of information regarding its meaning (the associates).
Municipal household solid waste collection strategies in an African megacity: Analysis of public private partnership performance in Lagos

Managing municipal solid waste is a pervasive urban problem globally. While several strategies have been applied for efficient municipal solid waste management in developing economies, their performance level has not been critically investigated. Among these strategies, the public private partnership has widest appeal. This study examines the performance of public private partnership in household solid waste collection in Lagos, Nigeria. We collected primary data using a municipal solid waste survey in three residential density areas of Lagos megacity. Descriptive and inferential statistics were used to analyse the data. Two indexes of service performance, namely the service reliability index and operational quality index, were created to produce evidence on public private partnership performance in municipal solid waste collection in Lagos. Results show that the average amount of household solid waste generation per week ranges between 22.75 kg in the medium residential density area and 30.39 kg in the high residential density region of the city. The estimated per capita waste generated in Lagos Megacity is 0.95 kg day−1. Regression models indicate that the public private partnership performance is significantly influenced by economic status, affordability, flexibility, consistency, cleanliness, coverage and accessibility, as well as number of waste collection vehicles, vehicle maintenance, capacity, trip rate, frequency, number of personnel and quality of personnel. Findings from this study reveal that Lagos residents have strong positive perception of public private partnership as a waste collection policy framework. The study has important policy and practical implications for urban waste management, public health and sustainability in developing economies.
Work-related musculoskeletal disorders in physical therapists: prevalence, severity, risks, and responses.

BACKGROUND AND PURPOSE Physical therapists are at risk for work-related musculoskeletal disorders (WMSDs). Little is known of how therapists respond or of what actions they take to prevent injury. The purpose of this study was to investigate the prevalence and severity of WMSDs in physical therapists, contributing risk factors, and their responses to injury. SUBJECTS As part of a larger study, a systematic sample of 1 in 4 therapists on a state register (n=824) was surveyed. METHODS An 8-page questionnaire was mailed to each subject. Questions investigated musculoskeletal symptoms, specialty areas, tasks and job-related risk factors, injury prevention strategies, and responses to injury. RESULTS Lifetime prevalence of WMSDs was 91%, and 1 in 6 physical therapists moved within or left the profession as a result of WMSDs. Younger therapists reported a higher prevalence of WMSDs in most body areas. Use of mobilization and manipulation techniques was related to increased prevalence of thumb symptoms. Risk factors pertaining to workload were related to a higher prevalence of neck and upper-limb symptoms, and postural risk factors were related to a higher prevalence of spinal symptoms. CONCLUSION AND DISCUSSION Strategies used to reduce work-related injury in industry may also apply to physical therapists. Increased risk of thumb symptoms associated with mobilization techniques suggests that further research is needed to establish recommendations for practice. The issues for therapists who move within or leave the profession are unknown, and further research is needed to better understand their needs and experiences.
Perfluorocarbon liquids in vitreoretinal surgery: a review of applications and toxicity

Since their introduction by Chang et al. in 1987, perfluorocarbon liquids (PFCLs) have become a useful tool in vitreoretinal surgery. They are synthetic compounds with carbon-fluorine chemical chains that have specific physico-chemical properties, which make them valuable for the intraoperative management of the retina by simplifying vitreoretinal surgical maneuvers in a variety of settings. These maneuvers include retinal detachments associated with proliferative vitreous retinopathy, following penetrating trauma, giant retinal tears, dislocated lenses or lens implants and complications from proliferative diabetic vitreoretinopathy. Purified PFCLs are generally considered to be biologically inert. Despite the stability of PFCLs during vitreoretinal surgery, several studies have indicated that these compounds may be associated with toxicity in ocular tissues. The purpose of this review is to report the use and toxicity of PFCLs in vitreoretinal surgery and to present the latest perspectives on modified PFCLs (hydrofluorocarbon liquids (HFCLs) and HFCL-oligomers).
Diagnosis and management of microscopic colitis.

OBJECTIVE To describe microscopic colitis (MC) and a stepwise approach to its diagnosis and management. QUALITY OF EVIDENCE MEDLINE was searched from January 1996 to August 2002. Controlled trials were sought, but due to their relative rarity, most articles cited are well designed retrospective studies and reviews. MAIN MESSAGE Microscopic colitis in both its collagenous and lymphocytic forms is a relatively common and important cause of diarrhea in middle-aged and elderly patients. It usually presents as chronic watery diarrhea. Results of endoscopic and radiologic examinations are normal; specific histologic findings are seen on colonic biopsy. Once the diagnosis is confirmed, we suggest a stepwise approach to therapy. First-line therapies include antidiarrheal agents; second-line include bismuth subsalicylates and budesonide; third-line include cholestyramine and 5-aminosalicylic acid agents. When patients fail to respond to these therapies, oral corticosteroids or immune modulatory therapy should be considered. For severe unresponsive cases, colectomy is the last resort. CONCLUSION Microscopic colitis is an important cause of chronic diarrhea. Once the diagnosis is confirmed, a stepwise approach to treatment is suggested.