Artificial Intelligence in Anterior Chamber Evaluation: A Systematic Review and Meta-Analysis.

PRCIS: In this meta-analysis of 6 studies and 5269 patients, deep learning algorithms applied to AS-OCT demonstrated excellent diagnostic performance for closed angle compared with gonioscopy, with a pooled sensitivity and specificity of 94% and 93.6%, respectively. PURPOSE: This study aimed to review the literature and compare the accuracy of deep learning algorithms (DLA) applied to anterior segment optical coherence tomography images (AS-OCT) against gonioscopy in detecting angle closure in patients with glaucoma. METHODS: We performed a systematic review and meta-analysis evaluating DLA in AS-OCT images for the diagnosis of angle closure compared with gonioscopic evaluation. PubMed, Scopus, Embase, Lilacs, Scielo, and Cochrane Central Register of Controlled Trials were searched. The bivariate model was used to calculate pooled sensitivity and specificity. RESULTS: The initial search identified 214 studies, of which 6 were included for final analysis. The total study population included 5269 patients. The combined sensitivity of the DLA compared with gonioscopy was 94.0% (95% CI: 83.8%-97.9%), whereas the pooled specificity was 93.6% (95% CI: 85.7%-97.3%). Sensitivity analyses removing each individual study showed a pooled sensitivity in the range of 90.1%-95.1%. Similarly, specificity results ranged from 90.3% to 94.5% with the removal of each individual study and recalculation of pooled specificity. CONCLUSION: DLA applied to AS-OCT has excellent sensitivity and specificity in the identification of angle closure. This technology may be a valuable resource in the screening of populations without access to experienced ophthalmologists who perform gonioscopy.

Myocardial and mitochondrial effects of the anhydrase carbonic inhibitor ethoxzolamide in ischemia-reperfusion.

We have previously demonstrated that inhibition of extracellularly oriented carbonic anhydrase (CA) isoforms protects the myocardium against ischemia-reperfusion injury. In this study, our aim was to assess the possible further contribution of CA intracellular isoforms examining the actions of the highly diffusible cell membrane permeant inhibitor of CA, ethoxzolamide (ETZ). Isolated rat hearts, after 20 min of stabilization, were assigned to the following groups: (1) Nonischemic control: 90 min of perfusion; (2) Ischemic control: 30 min of global ischemia and 60 min of reperfusion (R); and (3) ETZ: ETZ at a concentration of 100 µM was administered for 10 min before the onset of ischemia and then during the first 10 min of reperfusion. In additional groups, ETZ was administered in the presence of SB202190 (SB, a p38MAPK inhibitor) or chelerythrine (Chel, a protein kinase C [PKC] inhibitor). Infarct size, myocardial function, and the expression of phosphorylated forms of p38MAPK, PKCε, HSP27, and Drp1, and calcineurin Aß content were assessed. In isolated mitochondria, the Ca2+ response, Ca2+ retention capacity, and membrane potential were measured. ETZ decreased infarct size by 60%, improved postischemic recovery of myocardial contractile and diastolic relaxation increased P-p38MAPK, P-PKCε, P-HSP27, and P-Drp1 expression, decreased calcineurin content, and normalized calcium and membrane potential parameters measured in isolated mitochondria. These effects were significantly attenuated when ETZ was administered in the presence of SB or Chel. These data show that ETZ protects the myocardium and mitochondria against ischemia-reperfusion injury through p38MAPK- and PKCε-dependent pathways and reinforces the role of CA as a possible target in the management of acute cardiac ischemic diseases.

Altered gene expression in slc4a11-/- mouse cornea highlights SLC4A11 roles.

SLC4A11 is a H+/NH3/water transport protein, of corneal endothelial cells. SLC4A11 mutations cause congenital hereditary endothelial dystrophy and some cases of Fuchs endothelial corneal dystrophy. To probe SLC4A11's roles, we compared gene expression in RNA from corneas of 17-week-old slc4a11-/- (n = 3) and slc4a11+/+ mice (n = 3) and subjected to RNA sequencing. mRNA levels for a subset of genes were also assessed by quantitative real-time reverse transcription PCR (qRT RT-PCR). Cornea expressed 13,173 genes, which were rank-ordered for their abundance. In slc4a11-/- corneas, 100 genes had significantly altered expression. Abundant slc14a1 expression, encoding the urea transporter UT-A, suggests a significant role in the cornea. The set of genes with altered expression was subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, revealing that alterations clustered into extracellular region, cytoskeleton, cell adhesion and plasma membrane functions. Gene expression changes further clustered into classes (with decreasing numbers of genes): cell fate and development, extracellular matrix and cell adhesion, cytoskeleton, ion homeostasis and energy metabolism. Together these gene changes confirm earlier suggestions of a role of SLC4A11 in ion homeostasis, energy metabolism, cell adhesion, and reveal an unrecognized SLC4A11 role in cytoskeletal organization.

Familial Cases of PENS: A Review of the Literature.

Papular epidermal nevus with "skyline" basal cell layer (PENS) is a keratinocytic nevus that can occur sporadically or has a familial transmission. There are 5 families reported with PENS, in which there are 2 family members affected with each case. We present the sixth familial case, with the peculiarity of being the first time in which there are 3 family members with PENS, while reviewing the other cases described until now. In addition, we present a new histopathological finding, an inflammatory lichenoid infiltrate on the upper dermis in PENS lesions. This finding could be the result of trauma to the biopsied lesion, or it may represent a new inflammatory histological variant.

Comparative Evaluation of Coracoid Graft Dimensions in the Latarjet Surgery for Anterior Glenohumeral Instability.

Objectives The aim of the present study was to describe the dimensions of the coracoid grafts in our Latarjet surgeries and compare them with the results described in the literature. In addition, the feasibility of the 7-millimeter rule was verified. Methods Individuals with anterior glenohumeral instability with or without bone loss participated in the present study. The dimensions of 31 coracoid process grafts of patients who were submitted to the Latarjet surgical technique were measured with an analogical caliper and recorded for posterior analysis. Results The dimensions of the coracoid graft did not show statistically significant differences related to gender. The graft width obtained from our sample presented similarities with the dimensions reported in the literature. However, the length and thickness were smaller when compared to the reference study (Young et al, 2013). 15 The 7-millimeter rule was considered feasible regarding the graft dimensions obtained from our sample. Conclusion The coracoid graft dimensions were similar to the dimensions described in the literature regarding width, but the same was not found for length and thickness; and the 7-millimeter rule was feasible regarding the graft dimensions obtained from our sample.

Comparative Evaluation of Coracoid Graft Dimensions in the Latarjet Surgery for Anterior Glenohumeral Instability / Avaliação comparativa das dimensões do enxerto do coracoide na cirurgia de Latarjet para instabilidade glenoumeral anterior

Abstract Objectives The aim of the present study was to describe the dimensions of the coracoid grafts in our Latarjet surgeries and compare them with the results described in the literature. In addition, the feasibility of the 7-millimeter rule was verified. Methods Individuals with anterior glenohumeral instability with or without bone loss participated in the present study. The dimensions of 31 coracoid process grafts of patients who were submitted to the Latarjet surgical technique were measured with an analogical caliper and recorded for posterior analysis. Results The dimensions of the coracoid graft did not show statistically significant differences related to gender. The graft width obtained from our sample presented similarities with the dimensions reported in the literature. However, the length and thickness were smaller when compared to the reference study (Young et al, 2013).15 The 7-millimeter rule was considered feasible regarding the graft dimensions obtained from our sample. Conclusion The coracoid graft dimensions were similar to the dimensions described in the literature regarding width, but the same was not found for length and thickness; and the 7-millimeter rule was feasible regarding the graft dimensions obtained from our sample.

Resumo Objetivo O objetivo deste estudo foi descrever as dimensões do processo coracoide em nossas cirurgias de Latarjet e compará-las com os resultados descritos na literatura. Além disso, a viabilidade da regra dos 7 milímetros foi verificada. Métodos Indivíduos com instabilidade glenoumeral anterior com ou sem erosão óssea participaram deste estudo. As dimensões de 31 enxertos de processo coracoide de pacientes operados pela técnica de Latarjet foram mensuradas com um paquímetro analógico e registradas para análise posterior. Resultados As dimensões do processo coracoide não demonstraram diferença estatisticamente significativa de acordo com o sexo. A largura do enxerto obtida em nossa amostra apresentou semelhança com as dimensões descritas na literatura. No entanto, o comprimento e a espessura foram um pouco menores quando comparados com o estudo de referência (Young et al, 2013).15 A regra dos 7 milímetros foi considerada viável com as dimensões do enxerto obtidas em nossa amostra. Conclusão As dimensões do enxerto do coracoide foram similares às descritas na literatura em relação à largura, mas o mesmo não foi encontrado quanto ao comprimento e espessura; e a regra dos 7 milímetros demonstrou viabilidade com as dimensões do enxerto obtidas em nossa amostra.

Carbonic anhydrase II/sodium-proton exchanger 1 metabolon complex in cardiomyopathy of ob-/- type 2 diabetic mice.

Heart failure is the leading cause of death among diabetic people. Cellular and molecular entities leading to diabetic cardiomyopathy are, however, poorly understood. Coupling of cardiac carbonic anhydrase II (CAII) and Na+/H+ exchanger 1 (NHE1) to form a transport metabolon was analyzed in obese type 2 diabetic mice (ob-/-) and control heterozygous littermates (ob+/-). Echocardiography showed elevated systolic interventricular septum thickness and systolic posterior wall thickness in ob-/- mice at 9 and 16 weeks. ob-/- mice showed increased left ventricular (LV) weight/tibia length ratio and increased cardiomyocyte cross sectional area as compared to controls, indicating cardiac hypertrophy. Immunoblot analysis showed increased CAII expression in LV samples of ob-/-vs. ob+/- mice, and augmented Ser703 phosphorylation on NHE1 in ob-/- hearts. Reciprocal co-immunoprecipitation analysis showed strong association of CAII and NHE1 in LV samples of ob-/- mice. NHE1-dependent rate of intracellular pH (pHi) normalization after transient acid loading of isolated cardiomyocytes was higher in ob-/- mice vs. ob+/-. NHE transport activity was also augmented in cultured H9C2 rat cardiomyoblasts treated with high glucose/high palmitate, and it was normalized after CA inhibition. We conclude that the NHE1/CAII metabolon complex is exacerbated in diabetic cardiomyopathy of ob-/- mice, which may lead to perturbation of pHi and [Na+] and [Ca2+] handling in these diseased hearts.

Cardioprotection of benzolamide in a regional ischemia model: Role of eNOS/NO.

BACKGROUND: Recent studies from our laboratory show the cardioprotective action of benzolamide (BZ, carbonic anhydrase inhibitor) against ischemia-reperfusion injury. However, the mechanisms involved have not been fully elucidated. OBJECTIVE: To examine the participation of the endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) in the effects of BZ in a model of regional ischemia. METHODS: Isolated rat hearts perfused by Langendorff technique were submitted to 40 min of coronary artery occlusion followed by 60 min of reperfusion (IC). Other hearts received BZ during the first 10 min of reperfusion in absence or presence of L-NAME, NOS inhibitor. The infarct size (IS) and the post-ischemic recovery of myocardial function were measured. Oxidative/nitrosative damage were assessed by reduced glutathione (GSH) content, thiobarbituric acid reactive substances (TBARS) and 3-nitrotyrosine levels. The expression of phosphorylated forms of Akt, p38MAPK and eNOS, and the concentration of inducible nitric oxide synthase (iNOS) were also determined. RESULTS: BZ significantly decreased IS (6.2 ±â€¯0.5% vs. 34 ±â€¯4%), improved post-ischemic contractility, preserved GSH levels and diminished TBARS and 3-nitrotyrosine. In IC hearts, P-Akt, P-p38MAPK and P-eNOS decreased and iNOS increased. After BZ addition the levels of P-kinases and P-eNOS increased and iNOS decreased. Except for P-Akt, P-p38MAPK and iNOS, the effects of BZ were abolished by L-NAME. CONCLUSIONS: Our data demonstrate that the treatment with BZ at the onset of reperfusion was effective to reduce cell death, contractile dysfunction and oxidative/nitrosative damage produced by coronary artery occlusion. These BZ-mediated beneficial actions appear mediated by eNOS/NO-dependent pathways.

Retraction Note to: Compensatory role of the NBCn1 sodium/bicarbonate cotransporter on Ca2+-induced mitochondrial swelling in hypertrophic hearts.

The authors have retracted this article [1] because of modifications in the control lanes of Figs. 2a and 8a of the COX1 blot obtained for 18-week-old rats (rotation, horizontal flipping and re-use of the control lanes for the 35-week-old rats blot). In light of the concerns raised, the conclusions drawn in this article cannot be relied upon.

Benzolamide perpetuates acidic conditions during reperfusion and reduces myocardial ischemia-reperfusion injury.

During ischemia, increased anaerobic glycolysis results in intracellular acidosis. Activation of alkalinizing transport mechanisms associated with carbonic anhydrases (CAs) leads to myocardial intracellular Ca2+ increase. We characterize the effects of inhibition of CA with benzolamide (BZ) during cardiac ischemia-reperfusion (I/R). Langendorff-perfused isolated rat hearts were subjected to 30 min of global ischemia and 60 min of reperfusion. Other hearts were treated with BZ (5 µM) during the initial 10 min of reperfusion or perfused with acid solution (AR, pH 6.4) during the first 3 min of reperfusion. p38MAPK, a kinase linked to membrane transporters and involved in cardioprotection, was examined in hearts treated with BZ in presence of the p38MAPK inhibitor SB202190 (10 µM). Infarct size (IZ) and myocardial function were assessed, and phosphorylated forms of p38MAPK, Akt, and PKCε were evaluated by immunoblotting. We determined the rate of intracellular pH (pHi) normalization after transient acid loading in the absence and presence of BZ or BZ + SB202190 in heart papillary muscles (HPMs). Mitochondrial membrane potential (ΔΨm), Ca2+ retention capacity and Ca2+-mediated swelling after I/R were also measured. BZ, similarly to AR, reduced IZ, improved postischemic recovery of myocardial contractility, increased phosphorylation of Akt, PKCε, and p38MAPK, and normalized ΔΨm and Ca2+ homeostasis, effects abolished after p38MAPK inhibition. In HPMs, BZ slowed pHi recovery, an effect that was restored after p38MAPK inhibition. We conclude that prolongation of acidic conditions during reperfusion by BZ could be responsible for the cardioprotective benefits of reduced infarction and better myocontractile function, through p38MAPK-dependent pathways. NEW & NOTEWORTHY Carbonic anhydrase inhibition by benzolamide (BZ) maintains acidity, decreases infarct size, and improves postischemic myocardial dysfunction in ischemia-reperfusion (I/R) hearts. Protection afforded by BZ mimicked the beneficial effects elicited by an acidic solution (AR). Increased phosphorylation of p38MAPK occurs in I/R hearts reperfused with BZ or with AR. Mitochondria from I/R hearts possess abnormal Ca2+ handling and a more depolarized membrane potential compared with control hearts, and these changes were restored by treatment with BZ or AR.

Lower lip squamous cell carcinoma in patients with photosensitive disorders: Analysis of cases treated at the Brazilian National Cancer Institute (INCA) from 1999 to 2012.

BACKGROUND: Lower lip squamous cell carcinoma (LLSCC) is a common malignancy of the head and neck, being mainly a consequence of a chronic exposure to ultraviolet (UV) light solar radiation. Here, we evaluated the clinicopathological profile of patients with photosensitive disorders (xeroderma pigmentosum, lupus erythematosus and albinism) that developed LLSCC. MATERIAL AND METHODS: Data from patients who had a diagnosed LLSCC with a prior xeroderma pigmentosum, lupus erythematosus or albinism diagnosis that were treated at INCA from 1999 to 2012 were collected from patients medical records (n=16). The control group was composed of 68 patients with LLSCC without a medical history of photosensitivity. The clinicopathological data of this study population were collected and the association between these variables was analyzed by Fisher's exact test. Survival curves were constructed using the Kaplan-Meier method and compared by log-rank test. All statistical analyses were performed using SPSS statistics package. RESULTS: The mean age of patients in the photosensitive and non-photosensitive groups was 42 years and 67 years, respectively (p<0.0001). A previous history of malignant diseases was more common in the photosensitive group (p=0.001). In both groups, most tumors showed a pathological stage I/II disease. Overall and cancer-specific survival were not statistically different. However, disease-free interval showed a significant difference (p=0.01) between the photosensitive and non-photosensitive patients. CONCLUSIONS: Photosensitive patients presented LLSCC at earlier age but it usually was not the primary tumor in these patients. Furthermore, a more aggressive pathological behavior was not seen when compared with tumors from non-photosensitive patients. The disease-free interval was lower in photosensitive patients, as expected.

Efficacy and safety of very-low-calorie ketogenic diet: a double blind randomized crossover study.

OBJECTIVE: To verify safety respect to weight loss, cardiometabolic diseases of short-term Very low-calorie ketogenic diets (VLCKDs, <800 kcal day-1). PATIENTS AND METHODS: Randomized cross-over trial with placebo. The study had no. 2 dietary treatment (DT), conducted in two arms: (1) VLCKD1 in which 50% of protein intake is replaced with synthetic amino acids; (2) VLCKD2 with placebo. The VLCKDs (<800 kcal day-1) were different in term of protein content and quality each arm lasted three weeks (wks). Between the two arms a 3-wks washout period was performed to avoid additive effects on DT to follow. At the baseline, at start and end of each arm, all the subjects were evaluated for their health and nutritional status, by anthropometric analysis, body composition (Dual X-ray Absorptiometry (DXA), Bioimpedentiometry, biochemical evaluation, and Peroxisome Proliferator-Activated Receptor γ (PPAR) γ expression by transcriptomic analysis. RESULTS: After VLCKD1 were reduced: Body Mass Index (BMI) (Δ%=-11.1%, p=0.00), Total Body Water (TBW) (p<0.05); Android Fat Percentage (AFP) (Δ%=-1.8%, p=0.02); Android Fat Mass (AFM) (Δ%=-12.7%, p=0.00); Gynoid Fat Mass (GFM) (Δ%=-6.3%, p=0.01); Intermuscular Adipose Tissue (IMAT) (Δ%= -11.1%, p=0.00); Homeostasis Model Assessment of Insulin Re-sistance (HOMA-IR) (Δ%=-62.1%, p=0.01). After VLCKD1 a significant increase of uricemia, cre-atinine and aspartate aminotransferase (AST) (respectively Δ%=35%, p=0.01; Δ%=5.9%, p=0.02; Δ%=25.5%, p=0.03). After VLCKD2 were reduced: BMI (Δ%=-11.2%, p=0.00); AFM (Δ%=-14.3%, p=0.00); GFM (Δ%=-6.3%, p=0.00); Appendicular Skeletal Muscle Mass Index (ASMMI) (Δ%=-17.5%, p=0.00); HOMA-IR (Δ%=-59,4%, p=0.02). After VLCKD2, uricemia (Δ%=63.1%, p=0.03), and Vitamin D levels (Δ%=25.7%, p=0.02) were increased. No significant changes of car-diovascular disease (CVD) indexes were observed after DTs. No significant changes of PPARγ lev-el in any DTs. CONCLUSIONS: 21-days VLCKDs not impair nutritional state; not cause negative changes in global measurements of nutritional state including sarcopenia, bone mineral content, hepatic, renal and lipid profile.

Compensatory role of the NBCn1 sodium/bicarbonate cotransporter on Ca2+-induced mitochondrial swelling in hypertrophic hearts.

NBC Na+/HCO3- cotransporter (NBCn1) and NHE1 Na+/H+ exchanger have been associated with cardiac disorders and recently located in coronary endothelial cells (CEC) and cardiomyocytes mitochondria, respectively. Mitochondrial NHE1 blockade delays permeability transition pore (MPTP) opening and reduces superoxide levels, two critical events exacerbated in cells of diseased hearts. Conversely, activation of NBCn1 prevented apoptosis in CEC subjected to ischemic stress. We characterized the role of the NHE1 and NBCn1 transporters in heart mitochondria from hypertrophic (SHR) and control (Wistar) rats. Expression of NHE1 was analyzed in left ventricular mitochondrial lysates (LVML), by immunoblots. NHE1 expression increased by ~40% in SHR compared to control (P < 0.05, n = 4). To examine NHE1-mediated Na+/H+ exchange activity in cardiac hypertrophy, mitochondria were loaded with BCECF-AM dye and the maximal rate of pHm change measured after the addition of 50 mM NaCl. SHR mitochondria had greater changes in pHm compared to Wistar, 0.10 ± 0.01 vs. 0.06 ± 0.01, respectively (P < 0.05, n = 5). In addition, mitochondrial suspensions from SHR and control myocardium were exposed to 200 µM CaCl2 to induce MPTP opening (light-scattering decrease, LSD) and swelling. Surprisingly, SHR rats showed smaller LSD and a reduction in mitochondrial swelling, 67 ± 10% (n = 15), compared to control, 100 ± 8% (n = 13). NBC inhibition with S0859 (1 µM) significantly increased swelling in both control 139 ± 10% (n = 8) and SHR 115 ± 10% (n = 4). Finally, NBCn1 Na+/HCO3- cotransporter increased by twofold its expression in SHR LVML, compared to normal (P < 0.05, n = 5). We conclude that increased NBCn1 activity may play a compensatory role in hypertrophic hearts, protecting mitochondria from Ca2+-induced MPTP opening and swelling.

Patterns of virulence factor expression and antimicrobial resistance in Achromobacter xylosoxidans and Achromobacter ruhlandii isolates from patients with cystic fibrosis.

Achromobacter spp. are opportunistic pathogens increasingly recovered from adult patients with cystic fibrosis (CF). We report the characterization of 122 Achromobacter spp. isolates recovered from 39 CF patients by multilocus sequence typing, virulence traits, and susceptibility to antimicrobials. Two species, A. xylosoxidans (77%) and A. ruhlandii (23%) were identified. All isolates showed a similar biofilm formation ability, and a positive swimming phenotype. By contrast, 4·3% and 44·4% of A. xylosoxidans and A. ruhlandii, respectively, exhibited a negative swarming phenotype, making the swimming and swarming abilities of A. xylosoxidans significantly higher than those of A. ruhlandii. A. xylosoxidans isolates from an outbreak clone also exhibited significantly higher motility. Both species were generally susceptible to ceftazidime, ciprofloxacin, imipenem and trimethoprim/sulphamethoxazole and there was no significant difference in susceptibility between isolates from chronic or sporadic infection. However, A. xylosoxidans isolates from chronic and sporadic cases were significantly more resistant to imipenem and ceftazidime than isolates of the outbreak clone.

Carbonic anhydrase inhibitors reduce cardiac dysfunction after sustained coronary artery ligation in rats.

BACKGROUND: Two potent carbonic anhydrase (CA) inhibitors with widely differing membrane permeability, poorly diffusible benzolamide (BZ), and highly diffusible ethoxzolamide (ETZ) were assessed to determine whether they can reduce cardiac dysfunction in rats subjected to coronary artery ligation (CAL)-induced myocardial infarction. METHODS AND RESULTS: Rats with evidence of heart failure (HF) at 32 weeks following a permanent left anterior coronary artery occlusion were treated with placebo, BZ, or ETZ (4 mg kgday-1) for 4 weeks at which time left ventricular function and structure were evaluated. Lung weight/body weight (LW/BW) ratio increased in CAL rats by 17±1% vs. control, suggesting pulmonary edema. There was a trend for BZ and ETZ to ameliorate the increase in LW/BW by almost 50% (9±5% and 9±8%, respectively, versus CAL) (P=.16, NS). Echocardiographic assessment showed decreased left ventricular midwall shortening in HF rats, 21±1% vs. control 32±1%, which was improved by BZ to 29±1% and ETZ to 27±1%, and reduced endocardial shortening in HF rats 38±3% vs. control 62±1%, partially restored by BZ and ETZ to ~50%. Expression of the hypoxia-inducible membrane-associated CAIX isoform increased by ~60% in HF rat hearts, and this effect was blocked by ETZ. CONCLUSIONS: We conclude that CAL-induced myocardial interstitial fibrosis and associated decline in left ventricular function were diminished with BZ or ETZ treatment. The reductions in cardiac remodeling in HF with both ETZ and BZ CA inhibitors suggest that inhibition of a membrane-bound CA appears to be the critical site for this protection.