The role of Gata3 in renin cell identity.

Renin cells are precursors for other cell types in the kidney and show high plasticity in postnatal life in response to challenges to homeostasis. Our previous single-cell RNA-sequencing studies revealed that the dual zinc-finger transcription factor Gata3, which is important for cell lineage commitment and differentiation, is expressed in mouse renin cells under normal conditions and homeostatic threats. We identified a potential Gata3-binding site upstream of the renin gene leading us to hypothesize that Gata3 is essential for renin cell identity. We studied adult mice with conditional deletion of Gata3 in renin cells: Gata3fl/fl;Ren1dCre/+ (Gata3-cKO) and control Gata3fl/fl;Ren1d+/+ counterparts. Gata3 immunostaining revealed that Gata3-cKO mice had significantly reduced Gata3 expression in juxtaglomerular, mesangial, and smooth muscle cells, indicating a high degree of deletion of Gata3 in renin lineage cells. Gata3-cKO mice exhibited a significant increase in blood urea nitrogen, suggesting hypovolemia and/or compromised renal function. By immunostaining, renin-expressing cells appeared very thin compared with their normal plump shape in control mice. Renin cells were ectopically localized to Bowman's capsule in some glomeruli, and there was aberrant expression of actin-α2 signals in the mesangium, interstitium, and Bowman's capsule in Gata3-cKO mice. Distal tubules showed dilated morphology with visible intraluminal casts. Under physiological threat, Gata3-cKO mice exhibited a lower increase in mRNA levels than controls. Hematoxylin-eosin, periodic acid-Schiff, and Masson's trichrome staining showed increased glomerular fusion, absent cubical epithelial cells in Bowman's capsule, intraglomerular aneurysms, and tubular dilation. In conclusion, our results indicate that Gata3 is crucial to the identity of cells of the renin lineage.NEW & NOTEWORTHY Gata3, a dual zinc-finger transcription factor, is responsible for the identity and localization of renin cells in the kidney. Mice with a conditional deletion of Gata3 in renin lineage cells have abnormal kidneys with juxtaglomerular cells that lose their characteristic location and are misplaced outside and around arterioles and glomeruli. The fundamental role of Gata3 in renin cell development offers a new model to understand how transcription factors control cell location, function, and pathology.

[A hospital foundation for research on precariousness and social exclusion]. / Une fondation hospitalière pour la recherche sur la précarité et l'exclusion sociale.

The hospital in Nanterre (92) offers a wide range of services for the reception, orientation and medical care of people in precarious situations on a daily basis, both in the social medicine department and in other departments. The medical teams wanted to create a structure that could document and analyze the life trajectories and experiences of people in precarious situations, but above all innovate, propose adapted systems and evaluate them, in order to develop knowledge and practices. The hospital foundation for research on precariousness and social exclusion was thus created at the end of 2019 [1], with the structuring support of the Île-de-France regional health agency.

Determinants of renin cell differentiation: a single cell epi-transcriptomics approach.

Rationale: Renin cells are essential for survival. They control the morphogenesis of the kidney arterioles, and the composition and volume of our extracellular fluid, arterial blood pressure, tissue perfusion, and oxygen delivery. It is known that renin cells and associated arteriolar cells descend from FoxD1 + progenitor cells, yet renin cells remain challenging to study due in no small part to their rarity within the kidney. As such, the molecular mechanisms underlying the differentiation and maintenance of these cells remain insufficiently understood. Objective: We sought to comprehensively evaluate the chromatin states and transcription factors (TFs) that drive the differentiation of FoxD1 + progenitor cells into those that compose the kidney vasculature with a focus on renin cells. Methods and Results: We isolated single nuclei of FoxD1 + progenitor cells and their descendants from FoxD1 cre/+ ; R26R-mTmG mice at embryonic day 12 (E12) (n cells =1234), embryonic day 18 (E18) (n cells =3696), postnatal day 5 (P5) (n cells =1986), and postnatal day 30 (P30) (n cells =1196). Using integrated scRNA-seq and scATAC-seq we established the developmental trajectory that leads to the mosaic of cells that compose the kidney arterioles, and specifically identified the factors that determine the elusive, myo-endocrine adult renin-secreting juxtaglomerular (JG) cell. We confirm the role of Nfix in JG cell development and renin expression, and identified the myocyte enhancer factor-2 (MEF2) family of TFs as putative drivers of JG cell differentiation. Conclusions: We provide the first developmental trajectory of renin cell differentiation as they become JG cells in a single-cell atlas of kidney vascular open chromatin and highlighted novel factors important for their stage-specific differentiation. This improved understanding of the regulatory landscape of renin expressing JG cells is necessary to better learn the control and function of this rare cell population as overactivation or aberrant activity of the RAS is a key factor in cardiovascular and kidney pathologies.

Meibomian gland dysfunction and dry eye in keratoconus / Disfunção de glândulas de Meibomius e olho seco em ceratocone

ABSTRACT The objective of this report is to describe a case of meibomian gland dysfunction associated with keratoconus and to examine the importance of treatment for evaporative dry eye in cases of corneal ectasia. A 45-year-old man diagnosed as having keratoconus complained of burning, tearing, itching, and red eye. He had a history of penetrating corneal transplantation and wearing rigid contact lenses. The meibography revealed a severe meibomian gland dropout and normal tear meniscus height in both eyes. Objective propaedeutic tests are important tools for dry eye diagnosis and proper evaluation of ocular surface and tear film. In older patients, the classic signs of atopic conjunctivitis are not always present, and the causes of chronic rubbing must be further investigated. Treatment of underlying chronic inflammation such as dry eye, meibomian gland dysfunction, and blepharitis might be important to prevent keratoconus progression and guarantee symptom relief.

RESUMO O objetivo é relatar um caso de associação entre disfunção de glândulas de meibomius (DGM) e ceratocone, assim como ressaltar a importância do tratamento do olho seco evaporativo em casos de ectasia corneana. Paciente do sexo masculino de 45 anos com ceratocone e queixas de ardência, lacrimejamento, prurido e olho vermelho. O mesmo tem histórico de transplante de córnea penetrante e uso de lentes de contato rígidas. A meibografia revelou severa perda de glândulas de meibomius e menisco lacrimal normal em ambos os olhos. Testes propedêuticos objetivos são importantes ferramentas para diagnóstico de olho seco e apropriada avaliação da superfície ocular e filme lacrimal. Em pacientes mais velhos, os sinais clássicos de atopia não estão sempre presentes e investigações adicionais das causas de prurido crônico são necessárias. O tratamento da inflamação crônica subjacente como olho seco, disfunção de glândulas de meibomius e blefarite podem ser importantes para prevenir a progressão do ceratocone e garantir alívio dos sintomas.

Determinants of apprehension to return to sport after reconstruction of the anterior cruciate ligament: an exploratory observational retrospective study.

BACKGROUND: Only 65% of people return to a level of sport equivalent to that before after anterior cruciate ligament (ACL) surgery. Persisting apprehension may in part explain this observation. We aimed to describe characteristics of people with ACL-Return to Sport after Injury (RSI) scores ≥ 60/100 (low apprehension) at 6 months after injury and to identify variables independently associated with low apprehension at 6 months. METHODS: We conducted a single-center retrospective study. People who had surgery for an ACL rupture and who participated in an outpatient post-operative rehabilitation program were included consecutively. The ACL-RSI questionnaire was self-administered at 6 months after injury. Baseline characteristics of people with ACL-RSI scores ≥ 60/100 and < 60/100 were described. Multiple logistic regression was performed to identify baseline variables associated with low apprehension at 6 months. RESULTS: We included 37 participants: 13/37 (35.1%) were women and mean age was 27.2 (9.2) years. At 6 months, 21/37 (56.8%) had an ACL-RSI score ≥ 60/100. Participants who had an ACL-RSI score ≥ 60/100 more often received a preoperative rehabilitation (16/21 [76.2%] vs 5/16 [31.2%]), and had less often knee pain (7/21 [33.3%] vs 7/16 [43.7%]) and effusion (5/21 [23.8%] vs 8/16 [50.0%]) at 1 month after surgery, than participants who had an ACL-RSI score < 60/100. In the multivariate analysis, preoperative rehabilitation was associated with low apprehension at 6 months (OR [95% CI] = 0.107 [0.023 to 0.488], p = 0.002). CONCLUSIONS: Preoperative rehabilitation was independently associated with low apprehension at 6 months. TRIAL REGISTRATION: Not applicable.

The contact lens dry eyes questionnaire (CLDEQ-8) validation and ocular surface dysfunction among soft contact lens wearers / Validação do questionário de olho seco em lentes de contato (CLDEQ-8) e a disfunção de superfície ocular em usuários de lente de contato

ABSTRACT Purpose: To translate and validate the Contact Lens Dry Eyes Questionnaire (CLDEQ-8) to Portuguese language and to describe the impact of soft contact lenses on the ocular surface. Methods: We conducted a descriptive transversal study with the aim to: (1) translate and validate the CLDEQ-8 questionnaire to Portuguese language and (2) apply the CLDEQ-8 to a group of contact lens wearers along with a broad evaluation of the impact of soft contact lens on the ocular surface. The evaluation of the impact of soft contact lens was performed for a study population of 81 subjects, categorized in two groups: Group A: 61 contact lens wearers and Group B (control): 20 noncontact lens wearers. The study exclusion criteria were rigid contact lens wear, systemic or ocular diseases, the use of medications predisposing to ocular surface damage, and previous ocular surgeries. Results: For the CLDEQ-8 questionnaire translation and validation, Kappa agreement values were ³0.7 in all questions, implying a good agreement between the Portuguese and English language versions. Considering the ocular surface evaluation of the subjects, all parameters differed in Soft contact lens wearers when compared with the controls (p<0.05), except in those related to tear volume, such as the tear meniscus height and Schirmer test. Conclusions: This study provided a translated and validated Portuguese version of CLDEQ-8 questionnaire, which represents an important tool for the evolution of contact lens wearers. The broad evaluation of the ocular surface revealed an association between soft contact lens wearing and ocular surface disturbances.

RESUMO Objetivo: Traduzir e validar o questionário de olho seco e lentes de contato (CLDEQ-8) para o português e descrever o impacto das lentes de contato gelatinosas na superfície ocular. Métodos: Estudo transversal e descritivo com o objetivo de (1) traduzir e validar o CLDEQ-8 para o português e (2) aplicar o CLDEQ-8 em um grupo de usuários de lentes de contato, juntamente com uma ampla avaliação do impacto das lentes gelatinosas na superfície ocular. A avaliação do impacto das lentes gelatinosas foi realizada em uma amostra composta por 81 indivíduos, divididos em dois grupos: 61 usuários de lente de contato (Grupo A) e um grupo controle de 20 não usuários (Grupo B). Como critério de exclusão: usuário de lentes de contato rígidas, doenças sistêmicas ou oculares prévias, uso de medicamentos que podem causar danos a superfície ocular e cirurgias oculares prévias. Resultados: Para a tradução e validação do questionário CLDEQ-8, os valores de concordância Kappa foram iguais ou superiores a 0,7 em todas as perguntas, o que implica em uma boa concordância entre as versões em português e inglês. Considerando a avaliação da superfície ocular dos sujeitos, todos os parâmetros diferiram nos usuários de lente de contato em comparação com os controles (com p<0,05), exceto naqueles relacionados ao volume lacrimal, como altura do menisco lacrimal e teste de Schirmer. Conclusões: Este estudo forneceu uma versão traduzida para o português e validada do questionário CLDEQ-8, que representa uma importante ferramenta na avaliação de usuários de lente de contato. A avaliação da superfície ocular realizada demonstra a relação entre o uso de lentes de contato gelatinosas e os distúrbios da superfície ocular.

Comparative Studies of Renin-Null Zebrafish and Mice Provide New Functional Insights.

BACKGROUND: The renin-angiotensin system is highly conserved across vertebrates, including zebrafish, which possess orthologous genes coding for renin-angiotensin system proteins, and specialized mural cells of the kidney arterioles, capable of synthesising and secreting renin. METHODS: We generated zebrafish with CRISPR-Cas9-targeted knockout of renin (ren-/-) to investigate renin function in a low blood pressure environment. We used single-cell (10×) RNA sequencing analysis to compare the transcriptome profiles of renin lineage cells from mesonephric kidneys of ren-/- with ren+/+ zebrafish and with the metanephric kidneys of Ren1c-/- and Ren1c+/+ mice. RESULTS: The ren-/- larvae exhibited delays in larval growth, glomerular fusion and appearance of a swim bladder, but were viable and withstood low salinity during early larval stages. Optogenetic ablation of renin-expressing cells, located at the anterior mesenteric artery of 3-day-old larvae, caused a loss of tone, due to diminished contractility. The ren-/- mesonephric kidney exhibited vacuolated cells in the proximal tubule, which were also observed in Ren1c-/- mouse kidney. Fluorescent reporters for renin and smooth muscle actin (Tg(ren:LifeAct-RFP; acta2:EGFP)), revealed a dramatic recruitment of renin lineage cells along the renal vasculature of adult ren-/- fish, suggesting a continued requirement for renin, in the absence of detectable angiotensin metabolites, as seen in the Ren1YFP Ren1c-/- mouse. Both phenotypes were rescued by alleles lacking the potential for glycosylation at exon 2, suggesting that glycosylation is not essential for normal physiological function. CONCLUSIONS: Phenotypic similarities and transcriptional variations between mouse and zebrafish renin knockouts suggests evolution of renin cell function with terrestrial survival.

The contact lens dry eyes questionnaire (CLDEQ-8) validation and ocular surface dysfunction among soft contact lens wearers.

PURPOSE: To translate and validate the Contact Lens Dry Eyes Questionnaire (CLDEQ-8) to Portuguese language and to describe the impact of soft contact lenses on the ocular surface. METHODS: We conducted a descriptive transversal study with the aim to: (1) translate and validate the CLDEQ-8 questionnaire to Portuguese language and (2) apply the CLDEQ-8 to a group of contact lens wearers along with a broad evaluation of the impact of soft contact lens on the ocular surface. The evaluation of the impact of soft contact lens was performed for a study population of 81 subjects, categorized in two groups: Group A: 61 contact lens wearers and Group B (control): 20 noncontact lens wearers. The study exclusion criteria were rigid contact lens wear, systemic or ocular diseases, the use of medications predisposing to ocular surface damage, and previous ocular surgeries. RESULTS: For the CLDEQ-8 questionnaire translation and validation, Kappa agreement values were ³0.7 in all questions, implying a good agreement between the Portuguese and English language versions. Considering the ocular surface evaluation of the subjects, all parameters differed in Soft contact lens wearers when compared with the controls (p<0.05), except in those related to tear volume, such as the tear meniscus height and Schirmer test. CONCLUSIONS: This study provided a translated and validated Portuguese version of CLDEQ-8 questionnaire, which represents an important tool for the evolution of contact lens wearers. The broad evaluation of the ocular surface revealed an association between soft contact lens wearing and ocular surface disturbances.

Meibomian gland dysfunction and dry eye in keratoconus.

The objective of this report is to describe a case of meibomian gland dysfunction associated with keratoconus and to examine the importance of treatment for evaporative dry eye in cases of corneal ectasia. A 45-year-old man diagnosed as having keratoconus complained of burning, tearing, itching, and red eye. He had a history of penetrating corneal transplantation and wearing rigid contact lenses. The meibography revealed a severe meibomian gland dropout and normal tear meniscus height in both eyes. Objective propaedeutic tests are important tools for dry eye diagnosis and proper evaluation of ocular surface and tear film. In older patients, the classic signs of atopic conjunctivitis are not always present, and the causes of chronic rubbing must be further investigated. Treatment of underlying chronic inflammation such as dry eye, meibomian gland dysfunction, and blepharitis might be important to prevent keratoconus progression and guarantee symptom relief.

Inhibition of the renin-angiotensin system causes concentric hypertrophy of renal arterioles in mice and humans.

Inhibitors of the renin-angiotensin system (RAS) are widely used to treat hypertension. Using mice harboring fluorescent cell lineage tracers, single-cell RNA-Seq, and long-term inhibition of RAS in both mice and humans, we found that deletion of renin or inhibition of the RAS leads to concentric thickening of the intrarenal arteries and arterioles. This severe disease was caused by the multiclonal expansion and transformation of renin cells from a classical endocrine phenotype to a matrix-secretory phenotype: the cells surrounded the vessel walls and induced the accumulation of adjacent smooth muscle cells and extracellular matrix, resulting in blood flow obstruction, focal ischemia, and fibrosis. Ablation of the renin cells via conditional deletion of ß1 integrin prevented arteriolar hypertrophy, indicating that renin cells are responsible for vascular disease. Given these findings, prospective morphological studies in humans are necessary to determine the extent of renal vascular damage caused by the widespread use of inhibitors of the RAS.

Quality of life in keratoconus: evaluation with Keratoconus Outcomes Research Questionnaire (KORQ).

To assess the quality of life of keratoconus patients using the Keratoconus Outcomes Research Questionnaire (KORQ), translated and validated in Portuguese language. The KORQ is the only validated keratoconus specific questionnaire and has a high rating for its psychometric properties. This cross-sectional study enrolled 100 keratoconus patients from a tertiary referral eye hospital between April 2018 and June 2019. Associations between age, sex, allergic conjunctivitis, keratoconus stage, best-corrected visual acuity (BCVA), maximum simulated keratometry (Kmax), steep keratometry (K2), pachymetry, treatments performed, hydrops, and KORQ scores were evaluated using univariate (Wilcoxon test and the Kruskal Wallis test) and multivariate linear regression with stepwise backward modeling. Lower KORQ scores are associated with better quality of life, whereas, higher scores are associated with greater impairment of functional activities and symptoms. Among the 100 patients, mild, moderate, and severe keratoconus were observed in 15%, 46% and 39% of participants, respectively. Univariate analysis showed lower function scores values, with male sex (p < 0.05) and both functional and symptom scores were significantly associated with BCVA < 0.3 (LogMAR) (p < 0.05). Multivariate analysis indicated significantly lower functional scores in individuals with BCVA < 0.3 (LogMAR) (p < 0.001) and those with a history of crosslinking treatment (p = 0.022), while symptom scores were only significantly associated with only BCVA < 0.3 (LogMAR) (p < 0.001). In patients with keratoconus, BCVA in the better eye and history of crosslinkig were factors associated with better quality of life scores using the KORQ.

Do Patients With COVID-19 Benefit from Rehabilitation? Functional Outcomes of the First 100 Patients in a COVID-19 Rehabilitation Unit.

OBJECTIVE: To determine the benefits associated with brief inpatient rehabilitation for coronavirus 2019 (COVID-19) patients. DESIGN: Retrospective chart review. SETTING: A newly created specialized rehabilitation unit in a tertiary care medical center. PARTICIPANTS: Consecutive sample of patients (N=100) with COVID-19 infection admitted to rehabilitation. INTERVENTION: Inpatient rehabilitation for postacute care COVID-19 patients. MAIN OUTCOME MEASURES: Measurements at admission and discharge comprised a Barthel Activities of Daily Living Index (including baseline value before COVID-19 infection), time to perform 10 sit-to-stands with associated cardiorespiratory changes, and grip strength (dynamometry). Correlations between these outcomes and the time spent in the intensive care unit (ICU) were explored. RESULTS: Upon admission to rehabilitation, 66% of the patients were men, the age was 66±22 years, mean delay from symptom onset was 20.4±10.0 days, body mass index was 26.0±5.4 kg/m2, 49% had hypertension, 29% had diabetes, and 26% had more than 50% pulmonary damage on computed tomographic scans. The mean length of rehabilitation stay was 9.8±5.6 days. From admission to discharge, the Barthel index increased from 77.3±26.7 to 88.8±24.5 (P<.001), without recovering baseline values (94.5±16.2; P<.001). There was a 37% improvement in sit-to-stand frequency (0.27±0.16 to 0.37±0.16 Hz; P<.001), a 13% decrease in post-test respiratory rate (30.7±12.6 to 26.6±6.1; P=.03), and a 15% increase in grip strength (18.1±9.2 to 20.9±8.9 kg; P<.001). At both admission and discharge, Barthel score correlated with grip strength (ρ=0.39-0.66; P<.01), which negatively correlated with time spent in the ICU (ρ=-0.57 to -0.49; P<.05). CONCLUSIONS: Inpatient rehabilitation for COVID-19 patients was associated with substantial motor, respiratory, and functional improvement, especially in severe cases, although there remained mild persistent autonomy loss upon discharge. After acute stages, COVID-19, primarily a respiratory disease, might convert into a motor impairment correlated with the time spent in intensive care.

Deciphering the Identity of Renin Cells in Health and Disease.

Hypotension and changes in fluid-electrolyte balance pose immediate threats to survival. Juxtaglomerular cells respond to such threats by increasing the synthesis and secretion of renin. In addition, smooth muscle cells (SMCs) along the renal arterioles transform into renin cells until homeostasis has been regained. However, chronic unrelenting stimulation of renin cells leads to severe kidney damage. Here, we discuss the origin, distribution, function, and plasticity of renin cells within the kidney and immune compartments and the consequences of distorting the renin program. Understanding how chronic stimulation of these cells in the context of hypertension may lead to vascular pathology will serve as a foundation for targeted molecular therapies.

Ctcf is required for renin expression and maintenance of the structural integrity of the kidney.

Renin cells are crucial for the regulation of blood pressure and fluid electrolyte homeostasis. We have recently shown that renin cells possess unique chromatin features at regulatory regions throughout the genome that may determine the identity and memory of the renin phenotype. The 3-D structure of chromatin may be equally important in the determination of cell identity and fate. CCCTC-binding factor (Ctcf) is a highly conserved chromatin organizer that may regulate the renin phenotype by controlling chromatin structure. We found that Ctcf binds at several conserved DNA sites surrounding and within the renin locus, suggesting that Ctcf may regulate the transcriptional activity of renin cells. In fact, deletion of Ctcf in cells of the renin lineage led to decreased endowment of renin-expressing cells accompanied by decreased circulating renin, hypotension, and severe morphological abnormalities of the kidney, including defects in arteriolar branching, and ultimately renal failure. We conclude that control of chromatin architecture by Ctcf is necessary for the appropriate expression of renin, control of renin cell number and structural integrity of the kidney.

Megalin: A Novel Endocytic Receptor for Prorenin and Renin.

Megalin is an endocytic receptor contributing to protein reabsorption. Impaired expression or trafficking of megalin increases urinary renin and allowed the detection of prorenin, which normally is absent in urine. Here, we investigated (pro)renin uptake by megalin, using both conditionally immortalized proximal tubule epithelial cells and Brown Norway Rat yolk sac cells (BN16). To distinguish binding and internalization, cells were incubated with recombinant human (pro)renin at 4°C and 37°C, respectively. (Pro)renin levels were assessed by immunoradiometric assay. At 4°C, BN16 cells bound 3× more prorenin than renin, suggestive for a higher affinity of prorenin. Similarly, at 37°C, prorenin accumulated at 3- to 4-fold higher levels than renin in BN16 cells. Consequently, depletion of medium prorenin (but not renin) content occurred after 24 hours. No such differences were observed in conditionally immortalized proximal tubule epithelial cells, and M6P (mannose-6-phosphate) greatly reduced conditionally immortalized proximal tubule epithelial cells (pro)renin uptake, suggesting that these cells accumulate (pro)renin largely via M6P receptors. M6P did not affect (pro)renin uptake in BN16 cells. Yet, inhibiting megalin expression with siRNA greatly reduced (pro)renin binding and internalization by BN16 cells. Furthermore, treating BN16 cells with albumin, an endogenous ligand of megalin, also decreased binding and internalization of (pro)renin, while deleting the (pro)renin receptor affected the latter only. Exposing prorenin's prosegment with the renin inhibitor aliskiren dramatically increased prorenin binding, while after prosegment cleavage with trypsin prorenin binding was identical to that of renin. In conclusion, megalin might function as an endocytic receptor for (pro)renin and displays a preference for prorenin. Megalin-mediated endocytosis requires the (pro)renin receptor.

Comparing Resident Outcomes in Cataract Surgery at Different Levels of Experience.

PURPOSE: To evaluate outcomes of resident-performed cataract surgeries in different training levels in a retrospective case series. PATIENTS AND METHODS: A total of 730 surgeries performed by residents were evaluated into three groups: surgeries performed during residents' first semester of training in phacoemulsification (Level 1 - L1), surgeries performed during the second semester (Level 2 - L2), and surgeries performed during the third semester (Level 3 - L3). The primary outcome was the incidence of intraoperative complications in each group. Secondary outcomes were the comparisons between initial and final corrected distance visual acuity (CDVA), intraocular pressure (IOP), endothelial cell density (ECD), and central corneal thickness (CCT) in each group. Descriptive statistical analyses were employed in the presentation of the results using central tendency and variance measurements. RESULTS: The rate of complications within six weeks of follow-up was 24 out of 102 eyes (23.53%) in the L1 group, 63 out of 301 eyes (20.93%) in the L2 group, and 37 out of 327 (11.31%) in the L3 group (p=0.001). Posterior capsule rupture (PCR) was the most frequent intercurrence observed in all three semesters: it occurred in 12.7% of the surgeries in the first semester (13/102), 16.9% of surgeries in the second semester (51/301), and 9.5% of surgeries in the third semester (31/327). There was no significant difference in CDVA (p=0.298), ECD (p=0.067), IOP (p=0.217), or CCT (p=0.807) between the groups. CONCLUSION: When measured by rates of complications and by the aforementioned parameters, surgical competency was found to improve as surgical experience and frequency increased. Therefore, this study identified some patterns of skill development that can be applied to teaching strategies and better assist surgeons in training.

Effects of dual blockade in heart failure and renal dysfunction: Systematic review and meta-analysis.

OBJECTIVE: The effect of dual renin-angiotensin system (RAS) inhibition in heart failure (HF) is still controversial. Systematic reviews have shown that dual RAS blockade may reduce mortality and hospitalizations, yet it has been associated with the increased risk of renal dysfunction (RD). Surprisingly, although RD in patients with HF is frequent, the effect of combining RAS inhibitors in HF patients with RD has never been studied in a meta-analysis. METHODS: A systematic review and meta-analysis of randomized clinical trials involving HF patients with RD who received dual blockade analyzing death, cardiovascular (CV) death or HF hospitalization, and adverse events. RESULTS: Out of 2258 screened articles, 12 studies were included (34,131 patients). Compared with monotherapy, dual RAS inhibition reduced hazard ratio of death to 0.94 (p=0.07) and significantly reduced CV death or HF hospitalization to 0.89 (p=0.0006) in all individuals, and to 0.86 (p=0.005) in patients with RD and to 0.91 (p=0.04) without RD. Nevertheless, dual RAS blockade significantly increased the risk of renal impairment (40%), hyperkalemia (44%), and hypotension (42%), although discontinuation of treatment occurs only in 3.68% versus 2.19% (p=0.00001). CONCLUSIONS: Dual RAS inhibition therapy reduces the risk of CV death or HF hospitalization. However, cautions monitoring for specific adverse events may be warranted.

Stromal prorenin receptor is critical for normal kidney development.

Formation of the metanephric kidney requires coordinated interaction among the stroma, ureteric bud, and cap mesenchyme. The transcription factor Foxd1, a specific marker of renal stromal cells, is critical for normal kidney development. The prorenin receptor (PRR), a receptor for renin and prorenin, is also an accessory subunit of the vacuolar proton pump V-ATPase. Global loss of PRR is embryonically lethal in mice, indicating an essential role of the PRR in embryonic development. Here, we report that conditional deletion of the PRR in Foxd1+ stromal progenitors in mice (cKO) results in neonatal mortality. The kidneys of surviving mice show reduced expression of stromal markers Foxd1 and Meis1 and a marked decrease in arterial and arteriolar development with the subsequent decreased number of glomeruli, expansion of Six2+ nephron progenitors, and delay in nephron differentiation. Intrarenal arteries and arterioles in cKO mice were fewer and thinner and showed a marked decrease in the expression of renin, suggesting a central role for the PRR in the development of renin-expressing cells, which in turn are essential for the proper formation of the renal arterial tree. We conclude that stromal PRR is crucial for the appropriate differentiation of the renal arterial tree, which in turn may restrict excessive expansion of nephron progenitors to promote a coordinated and proper morphogenesis of the nephrovascular structures of the mammalian kidney.