A conserved switch controls virulence, sporulation, and motility in C. difficile.

Spore formation is required for environmental survival and transmission of the human enteropathogenic Clostridioides difficile. In all bacterial spore formers, sporulation is regulated through activation of the master response regulator, Spo0A. However, the factors and mechanisms that directly regulate C. difficile Spo0A activity are not defined. In the well-studied Bacillus species, Spo0A is directly inactivated by Spo0E, a small phosphatase. To understand Spo0E function in C. difficile, we created a null mutation of the spo0E ortholog and assessed sporulation and physiology. The spo0E mutant produced significantly more spores, demonstrating Spo0E represses C. difficile sporulation. Unexpectedly, the spo0E mutant also exhibited increased motility and toxin production, and enhanced virulence in animal infections. We uncovered that Spo0E interacts with both Spo0A and the toxin and motility regulator, RstA. Direct interactions between Spo0A, Spo0E, and RstA constitute a previously unknown molecular switch that coordinates sporulation with motility and toxin production. Reinvestigation of Spo0E function in B. subtilis revealed that Spo0E induced motility, demonstrating Spo0E regulation of motility and sporulation among divergent species. Further, 3D structural analyses of Spo0E revealed specific and exclusive interactions between Spo0E and binding partners in C. difficile and B. subtilis that provide insight into the conservation of this regulatory mechanism among different species.

Warming and shifts in litter quality drive multiple responses in freshwater detritivore communities.

Aquatic detritivores are highly sensitive to changes in temperature and leaf litter quality caused by increases in atmospheric CO2. While impacts on detritivores are evident at the organismal and population level, the mechanisms shaping ecological communities remain unclear. Here, we conducted field and laboratory experiments to examine the interactive effects of changes in leaf litter quality, due to increasing atmospheric CO2, and warming, on detritivore survival (at both organismal and community levels) and detritus consumption rates. Detritivore community consisted of the collector-gathering Polypedilum (Chironomidae), the scraper and facultative filtering-collector Atalophlebiinae (Leptophlebiidae), and Calamoceratidae (Trichoptera), a typical shredder. Our findings reveal intricate responses across taxonomic levels. At the organismal level, poor-quality leaf litter decreased survivorship of Polypedilum and Atalophlebiinae. We observed taxon-specific responses to warming, with varying effects on growth and consumption rates. Notably, species interactions (competition, facilitation) might have mediated detritivore responses to climate stressors, influencing community dynamics. While poor-quality leaf litter and warming independently affected detritivore larvae abundance of Atalophebiinae and Calamoceratidae, their combined effects altered detritus consumption and emergence of adults of Atalophlebiinae. Furthermore, warming influenced species abundances differently, likely exacerbating intraspecific competition in some taxa while accelerating development in others. Our study underscores the importance of considering complex ecological interactions in predicting the impact of climate change on freshwater ecosystem functioning. Understanding these emergent properties contributes to a better understanding of how detritivore communities may respond to future environmental conditions, providing valuable insights for ecosystem management and conservation efforts.

Laparoscopic Versus Open Gastrectomy for Advanced Gastric Cancer: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Laparoscopy-assisted gastrectomy (LAG) is a well-established surgical technique in treating patients with early gastric cancer. However, the efficacy and safety of LAG versus open gastrectomy (OG) in patients with advanced gastric cancer (AGC) remains unclear. METHODS: We systematically searched PubMed, Embase, and Cochrane Library in June 2023 for RCTs comparing LAG versus OG in patients with AGC. We pooled risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) for binary and continuous endpoints, respectively. We performed all statistical analyses using R software version 4.3.1 and a random-effects model. RESULTS: Nine RCTs comprising 3827 patients were included. There were no differences in terms of intraoperative complications (RR 1.14; 95% CI 0.72 to 1.82), number of retrieved lymph nodes (MD -0.54 lymph nodes; 95% CI -1.18 to 0.09), or mortality (RR 0.91; 95% CI 0.30 to 2.83). LAG was associated with a longer operative time (MD 49.28 minutes; 95% CI 30.88 to 67.69), lower intraoperative blood loss (MD -51.24 milliliters; 95% CI -81.41 to -21.06), shorter length of stay (MD -0.83 days; 95% CI -1.60 to -0.06), and higher incidence of pancreatic fistula (RR 2.44; 95% CI 1.08 to 5.50). Postoperatively, LAG was also superior to OG in reducing bleeding rates (RR 0.44; 95% CI 0.22 to 0.86) and time to first flatus (MD -0.27 days; 95% CI -0.47 to -0.07), with comparable results in anastomotic leakage, wound healing issues, major complications, time to ambulation, or time to first liquid intake. In the long-term analyses at 3 and 5 years, there were no significant differences between LAG and OG in terms of overall survival (RR 0.99; 95% CI 0.96 to 1.03) or relapse-free survival (RR 0.99; 95% CI 0.94 to 1.04). CONCLUSION: This meta-analysis of RCTs suggests that LAG may be an effective and safe alternative to OG for treating AGC; albeit, it may be associated with an increased risk for pancreatic fistula.

Antiradical capacity assay for hydrophobic substances using hemin-catalyzed luminol chemiluminescence in cationic micelles.

Antioxidant substances which can diminish the steady-state concentration of free radicals in vivo are important in the human dietary to diminish the deleterious effects of oxidative stress. As the potential of certain substances as antioxidants is difficult to be verified in vivo, simple chemical in vitro assays which test the potential of substances as antioxidants are of great importance for the screening of new antioxidants. These assays measure the capacity of a substance to suppress free radicals. We describe here an antiradical capacity assay, based on luminol chemiluminescence, in cationic micellar medium, allowing the capacity determination of hydrophobic compounds. The antiradical capacity of antioxidants is determined using the Trolox standard by the measurement of the light emission inhibition area caused by the addition of different antiradical concentrations. The obtained results are compared to the values determined using the scavenging of stable free radicals be the substances and shown to be similar for compounds like uric acid, rutin, and quercetin. However, for vitamin E, the luminol assay results in a considerably higher antiradical capacity than the assay with a stable free radical, which is rationalized by the higher reactivity of the radical generated in the luminol assay and a specific localization of vitamin E in the micellar medium.

The pH-responsive SmrR-SmrT system modulates C. difficile antimicrobial resistance, spore formation, and toxin production.

Clostridioides difficile is an anaerobic gastrointestinal pathogen that spreads through the environment as dormant spores. To survive, replicate, and sporulate in the host intestine, C. difficile must adapt to a variety of conditions in its environment, including changes in pH, the availability of metabolites, host immune factors, and a diverse array of other species. Prior studies showed that changes in intestinal conditions, such as pH, can affect C. difficile toxin production, spore formation, and cell survival. However, little is understood about the specific genes and pathways that facilitate environmental adaptation and lead to changes in C. difficile cell outcomes. In this study, we investigated two genes, CD2505 and CD2506, that are differentially regulated by pH to determine if they impact C. difficile growth and sporulation. Using deletion mutants, we examined the effects of both genes (herein smrR and smrT) on sporulation frequency, toxin production, and antimicrobial resistance. We determined that SmrR is a repressor of smrRT that responds to pH and suppresses sporulation and toxin production through regulation of the SmrT transporter. Further, we showed that SmrT confers resistance to erythromycin and lincomycin, establishing a connection between the regulation of sporulation and antimicrobial resistance.IMPORTANCEClostridioides difficile is a mammalian pathogen that colonizes the large intestine and produces toxins that lead to severe diarrheal disease. C. difficile is a major threat to public health due to its intrinsic resistance to antimicrobials and its ability to form dormant spores that are easily spread from host to host. In this study, we examined the contribution of two genes, smrR and smrT, on sporulation, toxin production, and antimicrobial resistance. Our results indicate that SmrR represses smrT expression, while production of SmrT increases spore and toxin production, as well as resistance to antibiotics.

Longitudinal evaluation of RTVue optical coherence tomography in patients with glaucoma and suspected glaucoma and stable visual fields / Avaliação longitudinal da tomografia de coerência óptica RTVue em pacientes glaucomatosos e suspeitos de glaucoma com campos visuais estáveis

ABSTRACT Purpose: To longitudinally compare isolated structural parameters obtained using RTVue optical coherence tomography in patients with glaucoma and suspected glaucoma with stable visual fields. Methods: All patients were required to have a reliable SITA Standard 24-2 Humphrey Visual Field test. Visual field stability was defined as having <5 points with p<5% and/or having no points with p<1% and/or p<0.05% in the glaucoma progression analysis comparison graph. Furthermore, the glaucoma assessment strategy was used in optical coherence tomography. Results: The study included 75 eyes from 75 patients, 43 of which had glaucoma and 32 had suspected glaucoma. The mean visual field intervals were 29.57 ± 9.65 months between the first and third tests. No visual field parameter variations (mean deviation, pattern standard deviation, and visual field index) and no retinal nerve fiber layer or optic disk parameter variations between the first and third tests were observed (p>0.05 for all), and no retinal nerve fiber layer parameter variations throughout the study were observed, except for optic disk parameters presenting with cup volume changes (p=0.004). However, ganglion complex cells presented a progressively decreased average ganglion cell complex parameter, with a variability of -0.98% ± 3.71% (p=0.04) between the first and third tests. By contrast, the global loss volume progressively increased throughout the study, with a variability of 14.71% ± 44.52% (p=0.04) between the first and third tests. The inferior ganglion cell complex parameter was significantly decreased between the first and third tests (p=0.02). Conclusion: The present findings suggest that patients with glaucoma or suspected glaucoma with stable visual fields may present structural ganglion complex cell progression as assessed using RTVue optical coherence tomography.

RESUMO Objetivo: Comparar longitudinalmente os parâmetros estruturais isolados obtidos através da tomografia de coerência óptica RTVue em pacientes glaucomatosos e suspeitos de glaucoma com campos visuais estáveis. Métodos: Todos os incluídos deveriam ter Campimetria Computadorizada Humphrey Sita Standard 24-2 confiáveis. A estabilidade campimétrica foi definida se apresentassem menos de cinco pontos com p<5% e/ou nenhum ponto com p<1% e/ou p<0,05% no gráfico de comparação do Glaucoma Progression Analysis. Para a tomografia de coerência óptica, foi utilizado a estratégia de avaliação para glaucoma. Resultados: Foram incluídos 75 olhos de 75 pacientes: 43 com glaucoma e 32 suspeitos. A média dos intervalos do campo visual entre o 1o e 3o exame, foi de 29,57 ± 9,65 meses. Não houve variação para os parâmetros do campo visual (desvio médio, desvio padrão e índice da função visual) entre o primeiro e o último exame (p>0,05 para todos). Não houve variação dos parâmetros da camada de fibras nervosas da retina ao longo do estudo, enquanto que para os parâmetros do disco óptico, apenas cup volume apresentou mudança (p=0,004). Em relação à camada de células ganglionares da retina, notou-se uma redução progressiva na espessura média da Ganglionar Complex Cells com uma variabilidade entre o primeiro e último exame de -0,98 ± 3,71% (p=0,04). Quanto ao Global loss volume, houve um aumento progressivo ao longo do estudo com uma variabilidade entre o primeiro e último exame de 14,71 ± 44,52% (p=0,04). O parâmetro inferior do Ganglionar Complex Cells também reduziu significativamente entre o 1o e 3o exames (p=0,02). Os demais parâmetros da tomografia de coerência óptica RTVue se mantiveram estáveis entre o 1o e 3o exames. Conclusão: Os presentes achados sugerem que pacientes glaucomatosos ou com suspeita de glaucoma e com campos visuais estáveis, podem apresentar progressão estrutural na camada de células ganglionares da retina avaliada por meio da tomografia de coerência óptica RTVue.

The pH-responsive SmrR-SmrT system modulates C. difficile antimicrobial resistance, spore formation, and toxin production.

Clostridioides difficile is an anaerobic gastrointestinal pathogen that spreads through the environment as dormant spores. To survive, replicate, and sporulate in the host intestine, C. difficile must adapt to a variety of conditions in its environment, including changes in pH, the availability of metabolites, host immune factors, and a diverse array of other species. Prior studies showed that changes in intestinal conditions, such as pH, can affect C. difficile toxin production, spore formation, and cell survival. However, little is understood about the specific genes and pathways that facilitate environmental adaptation and lead to changes in C. difficile cell outcomes. In this study, we investigated two genes, CD2505 and CD2506, that are differentially regulated by pH to determine if they impact C. difficile growth and sporulation. Using deletion mutants, we examined the effects of both genes (herein smrR and smrT ) on sporulation frequency, toxin production, and antimicrobial resistance. We determined that SmrR is a repressor of smrRT that responds to pH and suppresses sporulation and toxin production through regulation of the SmrT transporter. Further, we showed that SmrT confers resistance to erythromycin and lincomycin, establishing a connection between the regulation of sporulation and antimicrobial resistance. IMPORTANCE: C. difficile is a mammalian pathogen that colonizes the large intestine and produces toxins that lead to severe diarrheal disease. C. difficile is a major threat to public health due to its intrinsic resistance to antimicrobials and its ability to form dormant spores that are easily spread from host to host. In this study, we examined the contribution of two genes, smrR and smrT on sporulation, toxin production, and antimicrobial resistance. Our results indicate that SmrR represses smrT expression, while production of SmrT increases spore and toxin production, as well as resistance to antibiotics.

Glycine fermentation by C. difficile promotes virulence and spore formation, and is induced by host cathelicidin.

Clostridioides difficile is a leading cause of antibiotic-associated diarrheal disease. C. difficile colonization, growth, and toxin production in the intestine is strongly associated with its ability to use amino acids to generate energy, but little is known about the impact of specific amino acids on C. difficile pathogenesis. The amino acid glycine is enriched in the dysbiotic gut and is suspected to contribute to C. difficile infection. We hypothesized that the use of glycine as an energy source contributes to colonization of the intestine and pathogenesis of C. difficile. To test this hypothesis, we deleted the glycine reductase (GR) genes grdAB, rendering C. difficile unable to ferment glycine, and investigated the impact on growth and pathogenesis. Our data show that the grd pathway promotes growth, toxin production, and sporulation. Glycine fermentation also had a significant impact on toxin production and pathogenesis of C. difficile in the hamster model of disease. Furthermore, we determined that the grd locus is regulated by host cathelicidin (LL-37) and the cathelicidin-responsive regulator, ClnR, indicating that the host peptide signals to control glycine catabolism. The induction of glycine fermentation by LL-37 demonstrates a direct link between the host immune response and the bacterial reactions of toxin production and spore formation.

A bullous variant of central serous chorioretinopathy treated with oral spironolactone / Uma variante bolhosa da coriorretinopatia serosa central tratada com espironolactona oral

ABSTRACT We report the case of a 39-year-old male patient who presented with visual loss in the right eye for 6 weeks. The best-corrected visual acuity was counting fingers in the right eye and 20/30 in the left eye. The fundus examination demonstrated a right retinal detachment inferiorly extending to the fovea and a left macular serous detachment. After multimodal imaging study, the patient was diagnosed as having a bullous variant of central serous chorioretinopathy and treated with oral spironolactone associated with adjuvant laser photocoagulation. The retinal changes resolved after 6 months. The final visual acuity was 20/20 in both eyes.

RESUMO Relatamos o caso de um homem de 39 anos apresentando perda visual no olho direito há seis semanas. A melhor acuidade visual corrigida foi conta-dedos no olho direito e 20/30 no esquerdo. A fundoscopia demonstrou descolamento de retina direito inferiormente com extensão à fóvea e descolamento macular seroso à esquerda. Após estudos de imagem multimodal, o paciente foi diagnosticado com uma variante bolhosa de coriorretinopatia serosa central e tratado com espironolactona oral associada à fotocoagulação a laser adjuvante. As alterações retinianas resolveram após seis meses. A acuidade visual final foi 20/20 em ambos os olhos.

Cardiac Computed Tomographic Angiography Evaluation of Right Ventricle-Pulmonary Artery Conduits with Surgical Correlation.

Right ventricle-pulmonary artery (RV-PA) conduits are used in the treatment of certain congenital heart disease (CHD). RV-PA conduit complications might develop over time and require intervention. To evaluate how well cardiac computed tomographic angiography (CCTA) performs compared to transthoracic echocardiography (TTE) in evaluating RV-PA conduit complications by using surgical findings as the reference standard. A retrospective chart review of all patients over a 5-year period who underwent CCTA for RV-PA conduit evaluation was performed. Patient demographics and clinical data were recorded. Preoperative CCTA and TTE findings were compared to the operative findings for concordance or discordance. Forty-one patients were included, 51% females. The complications were conduit stenosis (28.68%), infection (7.17%) and aneurysm/pseudoaneurysm (6.15%). TTE and CCTA were consistently able to visualize focal conduit stenosis (96%). The greatest discrepancy between TTE and CCTA was in evaluating for aneurysm/pseudoaneurysm, where TTE detected only 2/6 (33%) compared to CCTA which detected 6/6 (100%) of the cases. However, TTE was slightly better at detecting conduit infection (3/7, 43%) compared to CCTA (2/7, 29%). Note that 5 out of 7 patients with endocarditis had bovine jugular graft. CCTA and TTE provide similar diagnostic accuracy evaluating certain types of RV-PA conduit complications. However, certain complications were only visualized on CCTA or TTE making both modalities complementary to each other during diagnostic evaluation.

A Conserved Switch Controls Virulence, Sporulation, and Motility in C. difficile.

Spore formation is required for environmental survival and transmission of the human enteropathogenic Clostridioides difficile . In all bacterial spore formers, sporulation is regulated through activation of the master response regulator, Spo0A. However, the factors and mechanisms that directly regulate C. difficile Spo0A activity are not defined. In the well-studied Bacillus species, Spo0A is directly inactivated by Spo0E, a small phosphatase. To understand Spo0E function in C. difficile , we created a null mutation of the spo0E ortholog and assessed sporulation and physiology. The spo0E mutant produced significantly more spores, demonstrating Spo0E represses C. difficile sporulation. Unexpectedly, the spo0E mutant also exhibited increased motility and toxin production, and enhanced virulence in animal infections. We uncovered that Spo0E interacts with both Spo0A and the toxin and motility regulator, RstA. Direct interactions between Spo0A, Spo0E, and RstA constitute a previously unknown molecular switch that coordinates sporulation with motility and toxin production. Reinvestigation of Spo0E function in B. subtilis revealed that Spo0E induced motility, demonstrating Spo0E regulation of motility and sporulation among divergent species. Further, we found that Spo0E orthologs are widespread among prokaryotes, suggesting that Spo0E performs conserved regulatory functions in diverse bacteria.

Prevalence, risk factors and evolution of diabetes mellitus after treatment in primary aldosteronism. Results from the SPAIN-ALDO registry.

PURPOSE: To evaluate the prevalence, risk factors and evolution of diabetes mellitus (DM) after targeted treatment in patients with primary aldosteronism (PA). METHODS: A retrospective multicenter study of PA patients in follow-up at 27 Spanish tertiary hospitals (SPAIN-ALDO Register). RESULTS: Overall, 646 patients with PA were included. At diagnosis, 21.2% (n = 137) had DM and 67% of them had HbA1c levels < 7%. In multivariate analysis, family history of DM (OR 4.00 [1.68-9.53]), the coexistence of dyslipidemia (OR 3.57 [1.51-8.43]) and advanced age (OR 1.04 per year of increase [1.00-1.09]) were identified as independent predictive factors of DM. Diabetic patients were on beta blockers (46.7% (n = 64) vs. 27.5% (n = 140), P < 0.001) and diuretics (51.1% (n = 70) vs. 33.2% (n = 169), p < 0.001) more frequently than non-diabetics. After a median follow-up of 22 months [IQR 7.5-63.0], 6.9% of patients developed DM, with no difference between those undergoing adrenalectomy and those treated medically (HR 1.07 [0.49-2.36], p = 0.866). There was also no significant difference in the evolution of glycemic control between DM patients who underwent surgery and those medically treated (p > 0.05). CONCLUSION: DM affects about one quarter of patients with PA and the risk factors for its development are common to those of the general population. Medical and surgical treatment provides similar benefit in glycemic control in patients with PA and DM.

Longitudinal evaluation of RTVue optical coherence tomography in patients with glaucoma and suspected glaucoma and stable visual fields.

PURPOSE: To longitudinally compare isolated structural parameters obtained using RTVue optical coherence tomography in patients with glaucoma and suspected glaucoma with stable visual fields. METHODS: All patients were required to have a reliable SITA Standard 24-2 Humphrey Visual Field test. Visual field stability was defined as having <5 points with p<5% and/or having no points with p<1% and/or p<0.05% in the glaucoma progression analysis comparison graph. Furthermore, the glaucoma assessment strategy was used in optical coherence tomography. RESULTS: The study included 75 eyes from 75 patients, 43 of which had glaucoma and 32 had suspected glaucoma. The mean visual field intervals were 29.57 ± 9.65 months between the first and third tests. No visual field parameter variations (mean deviation, pattern standard deviation, and visual field index) and no retinal nerve fiber layer or optic disk parameter variations between the first and third tests were observed (p>0.05 for all), and no retinal nerve fiber layer parameter variations throughout the study were observed, except for optic disk parameters presenting with cup volume changes (p=0.004). However, ganglion complex cells presented a progressively decreased average ganglion cell complex parameter, with a variability of -0.98% ± 3.71% (p=0.04) between the first and third tests. By contrast, the global loss volume progressively increased throughout the study, with a variability of 14.71% ± 44.52% (p=0.04) between the first and third tests. The inferior ganglion cell complex parameter was significantly decreased between the first and third tests (p=0.02). CONCLUSION: The present findings suggest that patients with glaucoma or suspected glaucoma with stable visual fields may present structural ganglion complex cell progression as assessed using RTVue optical coherence tomography.

Renal blood flow during exercise: understanding its measurement with Doppler ultrasound.

The sympathetic nervous system (SNS) has a critical role in continuously coordinating responses to stimuli internal and external to the human body by appropriately modulating the activity of the organs it innervates. The SNS is activated in response to various physiological stressors, including exercise, which can involve a significant increase in SNS activity. An increase in SNS activity directed toward the kidneys causes vasoconstriction of afferent arterioles within the kidneys. This sympathetically mediated renal vasoconstriction decreases renal blood flow (RBF), causing significant blood flow redistribution toward active skeletal muscles during exercise. In research studies, different modes, intensities, and durations of exercise have been used to investigate the sympathetically mediated RBF response to exercise, and several methodological approaches have been used to quantify RBF. Doppler ultrasound provides noninvasive, continuous, real-time measurements of RBF and has emerged as a valid and reliable technique to quantify RBF during exercise. This innovative methodology has been applied in studies in which the RBF response to exercise has been examined in healthy young and older adults and patient populations such as those with heart failure and peripheral arterial disease. This valuable tool has enabled researchers to produce clinically relevant findings that have furthered our understanding of the effect of SNS activation on RBF in populations of health and disease. Therefore, the focus of this narrative review is to highlight the use of Doppler ultrasound in research studies that have provided important findings furthering our knowledge of the impact of SNS activation on RBF regulation in humans.

Detection of anomalous aortic origin of a coronary artery (AAOCA) by echocardiogram: When does computed tomographic angiography add value?

BACKGROUND AND OBJECTIVE: There is limited literature comparing TTE and CCTA in children with suspected AAOCA. To determine the distribution of various coronary anomalies comparing TTE and CCTA data, and define the added value advanced imaging brings in clinical decision-making. MATERIALS AND METHODS: Retrospective review of data was obtained in patients aged 0-18 years who underwent TTE and CCTA for suspected AAOCA. Patient demographics, CCTA and TTE findings, and interventions performed were recorded. RESULTS: 100 consecutive patients were included (60% male), mean age 11 years (7 days-18 years old). In 93 patients, CCTA detected 94 anomalous coronaries. Definitive coronary abnormality was reported on TTE in 77 patients; 76 of which were confirmed by CCTA, 1 patient was found to have a normal variant. Suspected anomalous origin was reported in 16 patients on TTE, 13 of which were abnormal on CCTA. The coronary origin was not seen on TTE in 6 patients; of these, 3 had AAOCA on CCTA and 3 had hypoplastic RCA with left dominant system. Only 1 patient who had a normal TTE was found to have AAOCA on CCTA. CCTA was better than TTE in defining ostial characteristics and the course of the anomalous coronary artery, and detecting myocardial bridge. CONCLUSIONS: CCTA adds value in diagnosing AAOCA when the coronary origins are not well assessed or suspected anomalous origin is suggested on TTE. In addition, when a confident definitive diagnosis of AAOCA is reported on TTE, CCTA demonstrates better performance in determining additional features of AAOCA.

A multicenter prospective comparative study evaluating cataract surgery and endoscopic cyclophotocoagulation either with or without iStent inject implantation in Brazilian patients with glaucoma.

PURPOSE: Compare 12-month (12 M) safety and efficacy of endoscopic cyclophotocoagulation (ECP) + cataract surgery (Group 1) versus ECP + cataract surgery + iStent inject trabecular micro-bypass implantation (Group 2) in Brazilian patients with open-angle glaucoma (OAG). METHODS: This prospective, multicenter, comparative case series included patients with OAG and cataract who were randomized to receive treatment in Group 1 or Group 2. Outcomes included mean and percent reduction versus preoperative in intraocular pressure (IOP) and number of glaucoma medications; visual acuity; occurrence of adverse events; and rate of secondary surgeries. RESULTS: Preoperatively, Groups 1 and 2 had similar mean IOP (mean ± standard deviation 22.1 ± 3.6 and 22.0 ± 2.5 mmHg, respectively) and mean number of medications (3.3 ± 0.6 and 3.4 ± 0.6 medications, respectively). At all follow-up timepoints through 12 M, both groups achieved significant IOP and medication reductions versus preoperative (IOP p < 0.001 and number of medications p < 0.001 for both groups). At 12 M, IOP reductions were 24.2% (Group 1) and 43.6% (Group 2) (p < 0.001); mean medication reductions were 50.2% and 71.5%, respectively. Mean postoperative IOP and number of medications were higher in Group 1 than Group 2 (IOP p < 0.01 all visits, medication p < 0.01 at 6 M and 12 M). Adverse events were generally mild and infrequent in both groups. CONCLUSION: Both treatment groups (ECP + phacoemulsification, with/without iStent inject implantation) achieved significant and safe reductions in IOP and medications versus preoperative in Brazilian OAG patients. Percent reductions were significantly greater, and mean IOP and medications were significantly lower, in the group receiving iStent inject. CLINICAL TRIAL REGISTRATION (CTR): CAAE project identification #20053019.5.0000.5078. Protocol #3.587.147. Clinical Trial Database of the Federal University of Goiás, Brazil. Registration Date: September 19, 2019.

A bullous variant of central serous chorioretinopathy treated with oral spironolactone.

We report the case of a 39-year-old male patient who presented with visual loss in the right eye for 6 weeks. The best-corrected visual acuity was counting fingers in the right eye and 20/30 in the left eye. The fundus examination demonstrated a right retinal detachment inferiorly extending to the fovea and a left macular serous detachment. After multimodal imaging study, the patient was diagnosed as having a bullous variant of central serous chorioretinopathy and treated with oral spironolactone associated with adjuvant laser photocoagulation. The retinal changes resolved after 6 months. The final visual acuity was 20/20 in both eyes.

Familial forms and molecular profile of primary hyperaldosteronism / Formas familiares y perfil molecular del hiperaldosteronismo primario

Primary hyperaldosteronism (PAH) is the most frequent cause of secondary arterial hypertension. Most PAHs occur sporadically, but 5% of cases have a hereditary origin (familial PAH). Four forms of familial PAH have been described. Type I familial PAH is produced by a fusion of the CYP11B2 and CYP11B1 genes, in this way the synthesis of aldosterone becomes to be regulated by ACTH instead of by angiotensin II. In type II, III and IV familial PAH there is an increase in the transcription and expression of CYP11B2 responsible for aldosterone synthesis due to a germinal mutation in CLCN2, KCNJ5 and CACNA1H, respectively. On the other hand, somatic mutations have been identified in 50% of sporadic PAHs, with gain-of-function mutations at the level of KCNJ5, ATP1A1, ATP2B3 and CACNA1D being the most common. This review provides a detailed description of the different forms of familial PAH and the molecular profile of patients with sporadic PAH. (AU)

El hiperaldosteronismo primario (HAP) es la causa más frecuente de hipertensión arterial secundaria. La mayor parte de los HAP ocurren de forma esporádica, pero un 5% de los casos tienen un origen hereditario (HAP familiar). Se conocen 4 formas de HAP familiares. El HAP familiar tipo I se produce por una fusión de los genes CYP11B2 y CYP11B1, de esta forma la síntesis de aldosterona pasa a estar regulada por la ACTH en vez de por la angiotensina II. En el HAP familiar tipo II, III y IV se produce un aumento de la transcripción y expresión de CYP11B2, responsable de la síntesis de aldosterona debido a una mutación germinal en CLCN2, KCNJ5 y CACNA1H, respectivamente. Por otra parte, se han identificado mutaciones somáticas en un 50% de los HAP esporádicos, siendo las mutaciones de ganancia de función a nivel de KCNJ5, ATP1A1, ATP2B3 y CACNA1D las más frecuentes. En esta revisión se ofrece una descripción detallada de las distintas formas de HAP familiar y sobre el perfil molecular de los pacientes con HAP esporádico. (AU)

Estimating the Ideal Treatment Protocol and Success Predictors for Double-session Micropulse Transscleral Laser for Glaucoma Management.

Aim: To identify the ideal treatment protocol and success predictors for double-session micropulse transscleral (MP3) laser for glaucoma management. Materials and methods: Patients who underwent double-session MP3, with a minimum follow-up of 6 months, were retrospectively investigated. Logistic regression analysis was used to verify preoperative success predictors. The following comparisons were made: (1) Between eyes that obtained surgical success vs failure, (2) According to the time required for MP3, and (3) Considering only eyes that required retreatment. Results: A total of 191 eyes from 148 patients were included. The preoperative intraocular pressure (IOP) was significantly higher than at last follow-up visit (27.3 ± 6.9 vs 14.6 ± 6.0 mm Hg, p < 0.001). Success was observed in 90.5% of the eyes. On logistic regression analysis with preoperative IOP and MP3 time as independent variables, only previous IOP was identified as a statistically significant factor (p = 0.004), with lower IOP relating to higher success. Eyes that required lower MP3 time underwent more MP3 procedures than those with higher MP3 time (1.2 ± 0.5 vs 1.1 ± 0.3, p = 0.03). In the 36 eyes that underwent retreatment, preoperative IOP was higher (31.6 ± 7.4 vs 26.3 ± 6.4 mm Hg, p < 0.001); eyes with successful IOP treatment had a higher MP3 treatment time at the first surgery than eyes with failed IOP correction (364.1 ± 68.2 vs 330.0 ± 18.0 seconds, p = 0.02). Conclusion: Thus, an ideal double-session MP3 protocol should use a high laser energy at the first surgery, and a high preoperative IOP can be considered as a predictor of surgical failure. Clinical significance: This is the first study to give special attention to the double-session MP3 protocol and success predictors. How to cite this article: Magacho L, Lima FE, Ávila MP. Estimating the Ideal Treatment Protocol and Success Predictors for Double-session Micropulse Transscleral Laser for Glaucoma Management. J Curr Glaucoma Pract 2022;16(2):111-116.

Caveolin-1 influences mitochondrial plasticity and function in hepatic stellate cell activation.

Caveolin-1 (Cav-1) is an integral membrane protein present in all organelles, responsible for regulating and integrating multiple signals as a platform. Mitochondria are extremely adaptable to external cues in chronic liver diseases, and expression of Cav-1 may affect mitochondrial flexibility in hepatic stellate cells (HSCs) activation. We previously demonstrated that exogenous expression of Cav-1 was sufficient to increase some classical markers of activation in HSCs. Here, we aimed to evaluate the influence of exogenous expression and knockdown of Cav-1 on regulating the mitochondrial plasticity, metabolism, endoplasmic reticulum (ER)-mitochondria distance, and lysosomal activity in HSCs. To characterize the mitochondrial, lysosomal morphology, and ER-mitochondria distance, we perform transmission electron microscope analysis. We accessed mitochondria and lysosomal networks and functions through a confocal microscope and flow cytometry. The expression of mitochondrial machinery fusion/fission genes was examined by real-time polymerase chain reaction. Total and mitochondrial cholesterol content was measured using Amplex Red. To define energy metabolism, we used the Oroboros system in the cells. We report that GRX cells with exogenous expression or knockdown of Cav-1 changed mitochondrial morphometric parameters, OXPHOS metabolism, ER-mitochondria distance, lysosomal activity, and may change the activation state of HSC. This study highlights that Cav-1 may modulate mitochondrial function and structural reorganization in HSC activation, being a potential candidate marker for chronic liver diseases and a molecular target for therapeutic intervention.