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Summary: During aging and in retinal degenerative diseases, vulnerable retinal pigment epithelial (RPE) cells are subject to mitochondrial dysfunction, creating a need for accessibility to tools which can facilitate assessment of the ocular posterior pole bioenergetics. Here, we present a protocol for quantifying mitochondrial respiration in the posterior eye cup (RPE-choroid-sclera) of young and old mice. We describe steps for eye cup dissection, optimization of tissue size, drug concentrations, and cycle conditions using the XF Cell Mito Stress Test. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Advanced age is the most established risk factor for developing age-related macular degeneration (AMD), one of the leading causes of visual impairment in the elderly, in Western and developed countries. Similarly, after middle age, there is an exponential increase in pathologic molecular and cellular events that can induce senescence, traditionally defined as an irreversible loss of the cells ability to divide and most recently reported to also occur in select post-mitotic and terminally differentiated cells, such as neurons. Together these facts raise the question as to whether or not cellular senescence, may play a role in the development of AMD. A number of studies have reported the effect of ocular-relevant inducers of senescence using primarily in vitro models of poorly polarized, actively dividing retinal pigment epithelial (RPE) cell lines. However, in interpretating the data, the fidelity of these culture models to the RPE in vivo, must be considered. Fewer studies have explored the presence and/or impact of senescent cells in in vivo models that present with phenotypic features of AMD, leaving this an open field for further investigation. The goal of this review is to discuss current thoughts on the potential role of senescence in AMD development and progression, with consideration of the model systems used and their relevance to human disease.

Age-related macular degeneration (AMD) is a disease that affects the macula - the central part of the retina. It is a leading cause of irreversible vision loss in the elderly. AMD onset is marked by the presence of lipid- and protein-rich extracellular deposits beneath the retinal pigment epithelium (RPE), a monolayer of polarized, pigmented epithelial cells located between the photoreceptors and the choroidal blood supply. Progression of AMD to the late nonexudative "dry" stage of AMD, also called geographic atrophy, is linked to progressive loss of areas of the RPE, photoreceptors, and underlying choriocapillaris leading to a severe decline in patients' vision. Differential susceptibility of macular RPE in AMD and the lack of an anatomical macula in most lab animal models has promoted the use of in vitro models of the RPE. In addition, the need for high throughput platforms to test potential therapies has driven the creation and characterization of in vitro model systems that recapitulate morphologic and functional abnormalities associated with human AMD. These models range from spontaneously formed cell line ARPE19, immortalized cell lines such as hTERT-RPE1, RPE-J, and D407, to primary human (fetal or adult) or animal (mouse and pig) RPE cells, and embryonic and induced pluripotent stem cell (iPSC) derived RPE. Hallmark RPE phenotypes, such as cobblestone morphology, pigmentation, and polarization, vary significantly betweendifferent models and culture conditions used in different labs, which would directly impact their usability for investigating different aspects of AMD biology. Here the AMD Disease Models task group of the Ryan Initiative for Macular Research (RIMR) provides a summary of several currently used in vitro RPE models, historical aspects of their development, RPE phenotypes that are attainable in these models, their ability to model different aspects of AMD pathophysiology, and pros/cons for their use in the RPE and AMD fields. In addition, due to the burgeoning use of iPSC derived RPE cells, the critical need for developing standards for differentiating and rigorously characterizing RPE cell appearance, morphology, and function are discussed.

Abstract Background Comprehensiveness of primary care has been declining, and much of the blame has been placed on early-career family physicians and their practice choices. To better understand early-career family physicians’ practice choices in Canada, we sought to identify the factors that most influence their decisions about how to practice. Methods We conducted a qualitative study using framework analysis. Family physicians in their first 10 years of practice were recruited from three Canadian provinces: British Columbia, Ontario, and Nova Scotia. Interview data were coded inductively and then charted onto a matrix in which each participant’s data were summarized by code. Results Of the 63 participants that were interviewed, 24 worked solely in community-based practice, 7 worked solely in focused practice, and 32 worked in both settings. We identified four practice characteristics that were influenced (scope of practice, practice type and model, location of practice, and practice schedule and work volume) and three categories of influential factors (training, professional, and personal). Conclusions This study demonstrates the complex set of factors that influence practice choices by early-career physicians, some of which may be modifiable by policymakers (e.g., policies and regulations) while others are less so (e.g., family responsibilities). Participants described individual influences from family considerations to payment models to meeting community needs. These findings have implications for both educators and policymakers who seek to support and expand comprehensive care.

Background: Urinary stress incontinence occurs due to weakness of the urethral sphincter and/or weakness of the pelvic floor muscles. The purpose of this study is to investigate the complications of TOT surgery in the treatment of women with stress urinary February. Methods: This is a cross-sectional study that was conducted on women suffering from stress urinary incontinence who underwent TOT surgery in Rohani and Mehregan Hospitals of Babol between March 2010 and February 2019. In order to record early complications, the medical records available in the clinic were referred to for the examination of patients one week and two months after the operation. The late complications of the operation were also investigated at the time of entering the study. Also, satisfaction with the procedure was scored using a visual scale (score 0 to 100). SPSS version 26 software was used in this study. Also, the significance level is less than 0.05. Results: The study included 59 patients, the majority of whom were housewives (91.5%), had an education level below high school (74.6%), and were menopausal (71.2%). The average age of the participants is 54.92±9.40 years. The most common postoperative complications were Dyspareunia (20.3%), lower urinary symptoms (13.6%), and incontinency (10.2%). Also, the rarest complications were intraoperative injury to the urethra or bladder (1.7%), mild Vaginal erogenous (1.7%), pain at the operation site (3.4%), and need for adjuvant treatment (3.4%). In response to the question of whether you would recommend this surgery to others who have the same problem, 53 people (83.89%) responded positively. The average level of patients' satisfaction with the operation (on a scale of 0 to 100) was 88.64±23.44. According to the T-test, there is a statistically significant relationship between the incidence of postoperative complications and the level of patient satisfaction (P

Effective treatments and animal models for the most prevalent neurodegenerative form of blindness in elderly people, called age-related macular degeneration (AMD), are lacking. Genome-wide association studies have identified lipid metabolism and inflammation as AMD-associated pathogenic pathways. Given liver X receptors (LXRs), encoded by the nuclear receptor subfamily 1 group H members 2 and 3 (NR1H3 and NR1H2), are master regulators of these pathways, herein we investigated the role of LXR in human and mouse eyes as a function of age and disease and tested the therapeutic potential of targeting LXR. We identified immunopositive LXR fragments in human extracellular early dry AMD lesions and a decrease in LXR expression within the retinal pigment epithelium (RPE) as a function of age. Aged mice lacking LXR presented with isoform-dependent ocular pathologies. Specifically, loss of the Nr1h3 isoform resulted in pathobiologies aligned with AMD, supported by compromised visual function, accumulation of native and oxidized lipids in the outer retina, and upregulation of ocular inflammatory cytokines, while absence of Nr1h2 was associated with ocular lipoidal degeneration. LXR activation not only ameliorated lipid accumulation and oxidant-induced injury in RPE cells but also decreased ocular inflammatory markers and lipid deposition in a mouse model, thereby providing translational support for pursuing LXR-active pharmaceuticals as potential therapies for dry AMD.

Nanocomposites based on thermoplastic polyurethane (TPU) and poly lactic acid (PLA) with different weight ratios of 10:90 and 30:70 were prepared by solution method. Hydroxyapatite nanoparticles (n-HA) were used to enhance the physical and mechanical properties of the alloys. To prepare the nanocomposites, the percentages of n-HA varied between 1% and 5%. Different tests were used to investigate the properties of these nanocomposites. Scanning electron microscopy (SEM) analysis, which was used to study the morphology of the blends, showed that there were rough morphologies in between materials, and the results of the mapping test showed that the dispersion of nanoparticles in the polymer matrix was almost good. TGA thermal degradation test showed that the presence of TPU to some extent can affect the thermal stability properties, and with the increase in this material, the thermal properties are strengthened. The crystalline behavior of the samples showed that the presence of TPU and n-HA nanoparticles had negative effects on the crystalline properties. The study of viscoelastic behaviors showed that the presence of TPU enhances the viscous behavior in the sample and decreases the glass transition temperature, while the presence of nanoparticles increases the elastic properties and glass transition temperature. Tensile test showed that the presence of n-HA has a greater effect on the mechanical properties. Dynamic contact angle analysis using water and dimethylformamide (DMF) solvent showed that the existing TPU and n-HA led to major changes in the interaction surface of scaffolds. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analysis showed that increasing the amounts of TPU and HA increases cell viability. SEM cell interactions analysis showed that the surfaces of PLA90TPU10H5 and PLA70TPU30H5 samples are very good for the preparation of bone tissue scaffolds. Our findings indicated that the addition of n-HA into PLA/TPU blends could impart new features to the PLA matrix as a promising candidate for bone, cartilage, and tendon tissue engineering.

Women as an important stratum of society play a fundamental role in the creation, establishment and strengthening of families. So, paying attention to their mental health as the family guides has direct effects on the mental health of children, families and consequently the whole of society. Thus, the present study was performed to investigate the moderating effect of the economic situation on the relationship between problem solving skills and mental health in two groups of working women and housewives referring to Welfare Centers in the city of Karaj. Based on Morgan's sampling table, 199 working women and 192 housewives (totally 391) were selected by simple random sampling method. Then, Cassidy and Long (1996) Problem-Solving Style Questionnaire and Goldberg (1989) General Health Questionnaire were administered on the sample group, and data were analyzed using SPSS software (ver. 17). The results showed that the economy had an independent contribution in predicting the mental health of working women, but it was not capable to act as a moderating variable in relationship between problem-solving skill and mental health of working women. In addition, according to the results obtained from the housewife population, not only the economy does not have an independent contribution in the prediction of their mental health, but also it cannot act as a moderating variable in this relationship. But the problem-solving skill alone explains 23.8% of the variance of mental health in the sample population. In other words, problem-solving ability was effective in increasing the level of mental health. But the impact of economy as a moderating variable in the relationship between problem-solving skill and mental health of housewives and working women was not significant.

Adult-onset foveomacular dystrophy (AOFVD) is a retinal pattern dystrophy that may affect up to 1 in 7,400 individuals. There is much that is unknown regarding this disease’s epidemiology, risk factors for development, and rate of progression through its four stages. Advancements in retinal imaging over the past 15 years have enabled improved characterization of the different stages of AOFVD. These imaging advancements also offer new ways of differentiating AOFVD from phenotypically similar retinal diseases like age-related macular degeneration and Best disease. This review synthesizes the most recent discoveries regarding imaging correlates within AOFVD as well as risk factors for the development of AOFVD, complications of AOFVD, and treatment options. Our aim is to provide ophthalmologists a succinct resource so that they may offer clarity, guidance, and appropriate monitoring and treatments for their patients with suspected AOFVD.

The progression of autonomic dysfunction from peripheral autonomic neuropathy (PAN) to cardiovascular autonomic neuropathy, including diabetic autonomic neuropathy and advanced autonomic dysfunction, increases morbidity and mortality risks. PAN is the earliest stage of autonomic neuropathy. It typically involves small fiber disorder and often is an early component. Small fiber disorder (SFD) is an inflammation of the C-nerve fibers. Currently, the most universally utilized diagnostic test for SFD as an indicator of PAN is galvanic skin response (GSR), as it is less invasive than skin biopsy. It is important to correlate a patient’s symptoms with several autonomic diagnostic tests so as not to treat patients with normal findings unnecessarily. At a large suburban northeastern United States (Sicklerville, NJ) autonomic clinic, 340 consecutive patients were tested with parasympathetic and sympathetic (P&S) monitoring (P&S Monitor 4.0; Physio PS, Inc., Atlanta, GA, USA) with cardiorespiratory analyses, and TMFlow (Omron Corp., Hoffman Estates, Chicago, IL, USA) with LD Technology sudomotor test (SweatC™). This is a prospective, nonrandomized, observational, population study. All patients were less than 60 y/o and were consecutively tested, analyzed and followed from February 2018 through May 2020. P&S Monitoring is based on cardiorespiratory analyses and SweatC™ sudomotor testing is based on GSR. Overall, regardless of the stage of autonomic neuropathy, SweatC™ and P&S Monitoring are in concordance for 306/340 (90.0%) of patients from this cohort. The result is an 89.4% negative predictive value of any P&S disorder if the sudomotor GSR test is negative and a positive predictive value of 90.4% if the sudomotor testing is positive. In detecting early stages of autonomic neuropathy, P&S Monitoring was equivalent to sudomotor testing with high sensitivity and specificity and high negative and positive predictive values. Therefore, either testing modality may be used to risk stratify patients with suspected autonomic dysfunction, including the earliest stages of PAN and SFD. Moreover, when these testing modalities were normal, their high negative predictive values aid in excluding an underlying autonomic nervous system dysfunction.

Type 2 diabetes mellitus (DM) is a chronic metabolic disorder posing multifaceted challenges to global public health. Among its numerous complications, infected diabetic foot ulcers (IDFUs) represent a particularly debilitating consequence. Beyond cardiovascular implications, there is an emerging understanding of the interconnectedness among IDFUs, neuropathy, atherosclerosis, and dyslipidemia. IDFUs, peripheral neuropathy, and atherosclerosis share common risk factors and mechanistic pathways. The primary objective of this study was to characterize the lipid profiles in DM patients with IDFUs, comparing them with DM patients without foot ulcers, and with a control group of healthy subjects. The secondary objectives included evaluating apolipoprotein E (ApoE) levels across these study groups and comparing lipid profiles within IDFU subgroups. A total of 160 patients were assessed for this study. After applying exclusion criteria, 140 participants were included, divided into three groups: Group IDFU (80 patients with IDFUs), Group DM (32 patients with DM but no foot ulcers), and Group Controls (28 healthy controls). Compared to Group DM, Group IDFU demonstrated lower levels of high-density lipoprotein cholesterol (HDL-C) (30.9 ± 12.6 mg/dL vs. 40.8 ± 16.6 mg/dL, p = 0.002), but improved levels of ApoE (160.9 ± 68.4 mg/dL vs. 197.2 ± 69.6 mg/dL, p = 0.01), triglycerides (TG) (126.9 ± 56.2 mg/dL vs. 165.8 ± 79.0 mg/dL, p = 0.004), low-density lipoprotein cholesterol (LDL-C) (84.2 ± 32.3 mg/dL vs. 92.3 ± 39.3 mg/dL, p = 0.1), and total cholesterol (133.6 ± 43 mg/dL vs. 164.6 ± 44.4 mg/dL, p = 0.002). The IDFU patients exhibit improved lipid profiles, excepting HDL-C, which is unusual because IDFU follows complications related to dyslipidemia for DM patients. Anemia, impaired renal function, and elevated TG levels were identified as biomarkers for mortality among patients with IDFUs. The data suggest that a lower level of HDL-C and an improved lipid profile may indicate a systemic end-stage disease manifestation in DM patients with IDFUs.

Abstract We describe a modified allogenic intrastromal lenticule implantation technique for management of keratoconus (KCN). Patients with advanced KCN already scheduled for corneal transplantation were enrolled. An allogenic corneal lenticule was implanted inside a stromal pocket created by femtosecond laser. In three cases, the estimated refractive error of the recipient eyes was corrected on the donor lenticules using an Excimer laser. All operated eyes underwent corneal crosslinking at the time of surgery. This method was named “Femtosecond Laser-assisted Allogenic Stromal Keratoplasty Without and With Excimer Laser-assisted Donor Keratomileusis”; briefly called FASK and FASK Plus EDK, respectively. Two out of five patients were satisfied with the results. There was a decrease in the average simulated keratometric values as well as myopia when FASK Plus EDK was performed. Increased corneal thickness was achieved in all cases. Graft edema gradually decreased over weeks but interface wrinkling and lenticule folds in the visual axis remained as a problem during follow-up period. No other complications were encountered.

Objectives: The lack of effective treatments for coronavirus disease 2019 (COVID-19) has mandated the repurposing of several drugs, including antiretrovirals and remdesivir (RDV). These compounds may induce acute kidney injury and are not recommended in patients with poor renal function, such as kidney transplant (KTx) recipients. Methods: The records of 42 KTx recipients with COVID-19 were reviewed. Some of them were receiving antiretrovirals (n = 10) or RDV (n = 8) as part of COVID-19 management. Most patients were male (71%) and their median age was 52 years. The median glomerular filtration rate in these patients was 56 ml/min. Regarding disease severity, 36% had mild disease, 19% had moderate disease, 31% had severe disease, and 12% had critical disease. Subgroups, i.e., patients receiving antiretrovirals, RDV, or no antivirals, were comparable in terms of patient age, comorbidities, and immunosuppression. Results: Seven patients (16.6%) died during hospitalization. Acute kidney injury was found in 24% of KTx recipients at admission. Upon discharge, estimated glomerular filtration rate (eGFR) increased in 32% and decreased in 39% of the KTx recipients compared with the admission rate. The decrease was more prevalent in the RDV group (80%) compared with KTx recipients without any antiviral treatment (29%) (p

Background: Endoscopic retrograde cholangiopancreatography (ERCP) represents a major pivotal point in gastrointestinal endoscopy. Little is known about acute kidney injury (AKI) post-ERCP. This study analyses the incidence, risk factors, and prognosis of post-ERCP AKI. Methods: A total of 396 patients were prospectively studied. AKI was defined by an increase in serum creatinine (SCr) ≥ 0.3 mg/dL or by an increase in SCr ≥ 50% in the first 48 h post-ERCP. Logistic regression analysis was used to identify the predictors of AKI and in-hospital mortality. A two-tailed p value < 0.05 was considered significant. Results: One hundred and three patients (26%) developed post-ERCP AKI. Estimated glomerular filtration rate (adjusted odds ratio (aOR) = 0.95, 95% confidence interval (CI): 0.94–0.96, p < 0.001), nonrenal Charlson Comorbidity Index (Aor = 1.19, 95% CI: 1.05–1.35, p = 0.006), choledocholithiasis (aOR = 4.05, 95% CI: 1.98–8.29, p < 0.001), and bilirubin (aOR = 1.1, 95% CI: 1.05–1.15, p < 0.001) were associated with post-ERCP AKI. Post-ERCP AKI was associated with longer hospital stay (p < 0.001) and with increased in-hospital mortality (7.76% versus 0.36%, p < 0.001). Moderate-to-severe (stage 2 and 3) AKI was independently associated with in-hospital mortality (aOR = 6.43, 95% CI: 1.48–27.88, p < 0.013). Conclusions: Post-ERCP AKI represented an important complication associated with longer hospital stay. Moderate-to-severe post-ERCP AKI was an independent risk factor for in-hospital mortality.

In the original publication [...]

Purpose: Micrometer-sized spherules formed of hydroxyapatite or whitlockite were identified within extracellular deposits that accumulate in the space between the basal lamina (BL) of retinal pigment epithelium (RPE) and the inner collagenous layer of Bruch’s membrane (sub-RPE–BL space). This investigation aimed to characterize the morphologic features, structure, and distribution of these spherules in aged human eyes with and without clinical indications of age-related macular degeneration (AMD). Design: Experimental study. Participants: Five human eyes with varying degrees of sub-RPE–BL deposits were obtained from the University College London Institute of Ophthalmology and Moorfield’s Eye Hospital Tissue Repository or the Advancing Sight Network. Two eyes were reported as having clinical indications of AMD (age, 76–87 years), whereas 3 were considered healthy (age, 69–91 years). Methods: Cadaveric eyes with sub-RPE–BL deposits were embedded in paraffin wax and sectioned to a thickness of 4-10 μm. Spherules were identified and characterized using high-resolution scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy, and time-of-flight secondary ion mass spectroscopy. Main Outcome Measures: High-resolution scanning electron micrographs of spherules, the size-frequency distribution of spherules including average diameter, and the distribution of particles across the central-peripheral axis. Elemental maps and time-of-flight secondary ion mass spectra also were obtained. Results: The precipitation of spherules is ubiquitous across the central, mid-peripheral, and far-peripheral axis in aged human eyes. No significant difference was found in the frequency of spherules along this axis. However, statistical analysis indicated that spherules exhibited significantly different sizes in these regions. In-depth analysis revealed that spherules in the sub-RPE–BL space of eyes with clinical signs of AMD were significantly larger (median diameter, 1.64 μm) than those in healthy aged eyes (median diameter, 1.16 μm). Finally, spherules showed great variation in surface topography and internal structure. Conclusions: The precipitation of spherules in the sub-RPE–BL space is ubiquitous across the central–peripheral axis in aged human eyes. However, a marked difference exists in the size and frequency of spherules in eyes with clinical signs of AMD compared to those without, suggesting that the size and frequency of spherules may be associated with AMD.

The democratic environment in Romania after 1989 witnessed the emergence of an unprecedented number of public discourses engaged with the re-evaluation of communism. In line with recent contributions to cultural memory studies (Aleida Assmann, Astrid Erll), this essay tries to assess the role that fiction played in reshaping the communist past and engaging with the post-communist present. Narratives written by Dan Lungu, Radu Pavel Gheo and Vasile Ernu, some of the most representative writers of the Romanian post-1989 era, are examined against the backdrop of public debates regarding the opposition between democracy and totalitarianism, progression and nostalgia, the 'civilized West' and the 'provincial' East. In reaction to the pressure of ideological discourses, this article argues that literature remains a privileged site where alternative versions of memory can intertwine and negotiate their claims. Literary texts that reshape cultural perceptions fulfil the 'mnemonic multiperspectivity' function of the public discourse with particular focus on recovering the marginal voices that are often disregarded by classic historiography. [ABSTRACT FROM AUTHOR]