Identification of Tensin-3 as a MALT1 substrate that controls B cell adhesion and lymphoma dissemination.

The protease MALT1 promotes lymphocyte activation and lymphomagenesis by cleaving a limited set of cellular substrates, most of which control gene expression. Here, we identified the integrin-binding scaffold protein Tensin-3 as a MALT1 substrate in activated human B cells. Activated B cells lacking Tensin-3 showed decreased integrin-dependent adhesion but exhibited comparable NF-κB1 and Jun N-terminal kinase transcriptional responses. Cells expressing a noncleavable form of Tensin-3, on the other hand, showed increased adhesion. To test the role of Tensin-3 cleavage in vivo, mice expressing a noncleavable version of Tensin-3 were generated, which showed a partial reduction in the T cell-dependent B cell response. Interestingly, human diffuse large B cell lymphomas and mantle cell lymphomas with constitutive MALT1 activity showed strong constitutive Tensin-3 cleavage and a decrease in uncleaved Tensin-3 levels. Moreover, silencing of Tensin-3 expression in MALT1-driven lymphoma promoted dissemination of xenografted lymphoma cells to the bone marrow and spleen. Thus, MALT1-dependent Tensin-3 cleavage reveals a unique aspect of the function of MALT1, which negatively regulates integrin-dependent B cell adhesion and facilitates metastatic spread of B cell lymphomas.

The protease activity of the paracaspase MALT1 is controlled by monoubiquitination.

The protease activity of the paracaspase MALT1 is central to lymphocyte activation and lymphomagenesis, but how this activity is controlled remains unknown. Here we identify a monoubiquitination of MALT1 on Lys644 that activated the protease function of MALT1. Monoubiquitinated MALT1 had enhanced protease activity, whereas a ubiquitination-deficient MALT1 mutant with replacement of that lysine with arginine (MALT1(K644R)) had less protease activity, which correlated with impaired induction of interleukin 2 (IL-2) via the T cell antigen receptor in activated T cells. Expression of MALT1(K644R) diminished the survival of cells derived from diffuse large B cell lymphoma of the activated B cell-like subtype (ABC DLBCL), which require constitutive protease activity of MALT1 for survival. Thus, monoubiquitination of MALT1 is essential for its catalytic activation and is therefore a potential target for the treatment of ABC-DLBCL and for immunomodulation.

Evidence That Peripheral Leptin Resistance in Omental Adipose Tissue and Liver Correlates with MASLD in Humans.

Leptin regulates lipid metabolism, maximizing insulin sensitivity; however, peripheral leptin resistance is not fully understood, and its contribution to metabolic dysfunction-associated steatotic liver disease (MASLD) is unclear. This study evaluated the contribution of the leptin axis to MASLD in humans. Forty-three participants, mostly female (86.04%), who underwent cholecystectomy were biopsied. Of the participants, 24 were healthy controls, 8 had MASLD, and 11 had metabolic dysfunction-associated steatohepatitis (MASH). Clinical and biochemical data and the gene expression of leptin, leptin receptor (LEPR), suppressor of cytokine signaling 3 (SOCS3), sterol regulatory element-binding transcription factor 1 (SREBF1), stearoyl-CoA desaturase-1 (SCD1), and patatin-like phospholipase domain-containing protein 2 (PNPLA2), were determined from liver and adipose tissue. Higher serum leptin and LEPR levels in the omental adipose tissue (OAT) and liver with MASH were found. In the liver, LEPR was positively correlated with leptin expression in adipose tissue, and SOCS3 was correlated with SREBF1-SCD1. In OAT, SOCS3 was correlated with insulin resistance and transaminase enzymes (p < 0.05 for all. In conclusion, we evidenced the correlation between the peripheral leptin resistance axis in OAT-liver crosstalk and the complications of MASLD in humans.

Atomic force microscopy for the evaluation of corneal surface roughness after femtosecond laser flap creation and excimer ablation.

INTRODUCTION: It is well known that the femtosecond laser lamellar cut induces some degree of surface roughness. Nevertheless, as in femtosecond laser-assisted LASIK (FS-LASIK), an excimer LASIK ablation is performed, and the post-ablation stromal bed should show some degree of smoothening. We decided to compare, using atomic force microscopy (AFM), the roughness of the corneal stromal bed, after a femtosecond lasers device flap was created with or without an excimer myopic ablation. METHODS: Using 6 freshly enucleated porcine eyes, we created in every eye a flap using a femtosecond laser. Additionally, in 3 eyes, an excimer laser ablation to correct-3 diopters (D) was made. AFM imaging of the remaining corneal stroma was performed. Ten different square areas of 20 µm x 20 µm at the central area of the stroma of each corneal sample were studied. The roughness parameters used were the root-mean-square deviation from a perfectly flat surface. RESULTS: The RMS deviation was 360 ± 120 nm in femtosecond laser only, and 110 ± 20 nm in those cases where excimer is also involved (p < 0.0001). CONCLUSIONS: Our results show that the roughness of the surface treated with excimer is clearly lower than in the group with no excimer ablation; thus, the application of laser excimer after a flap created by femtosecond laser seems to soften the nano-irregularities created by this technique.

Femtosecond LASIK for the correction of low and high myopic astigmatism.

INTRODUCTION: Higher preoperative myopic astigmatism is associated with a higher probability of retreatment due to patient dissatisfaction as a result of residual cylindrical error. Nonetheless, retreatment is safe and the final clinical results are comparable to those of patients with lower preoperative astigmatism who were satisfied with the primary treatment. Our purpose is to compare the efficacy and safety of femtosecond LASIK (FS-LASIK) for the refractive correction of patients with low (< 1.5 Diopters (D) versus high (≥ 1.5 D) myopic astigmatism. METHODS: Retrospective observational study of 841 eyes of 825 eligible patients treated with FSLASIK for the correction of simple or compound myopic astigmatism. Outcome measures included residual error, best corrected and uncorrected distance visual acuity (BCVA and UCVA), efficacy and safety 3 months after the primary procedure or the retreatment. RESULTS: Of 841 eyes in total, 432 (51.37%) had < 1.5 D (Group 1) and 409 (48.63%) had ≥ 1.5 D (Group 2) preoperative myopic astigmatism. The efficacy index of primary treatment was 0.94 ± 0.18 in Group 1 and 0.89 ± 0.22 in Group 2 (P = 0.001). Of 138 eyes (16.41%) that were retreated due to dis-satisfaction related to residual refractive error, 28 belonged to Group 1 (6.5%) and 110 (26.9%) to Group 2 (P < 0.001). Following retreatment, small but statistically significant differences in the residual mean postoperative cylinder (-0.08 ± 0.24 vs -0.27 ± 0.46 D, P = 0.001) and UCVA (1.11 vs 0.96, P = 0.0001) were detected for Groups 1 and 2, respectively. However, there were no statistically significant differences in the safety and efficacy indices. CONCLUSION: Following FS-LASIK, eyes with myopic astigmatism ≥ 1.5 D have approximately four times more chances of undergoing retreatment due to dis-satisfaction caused by residual refractive error compared to eyes with myopic astigmatism < 1.5 D. However, the clinical results after retreatment are highly satisfactory and comparable in both groups.

Atomic force microscopy comparative analysis of the surface roughness of two posterior chamber phakic intraocular lens models: ICL versus IPCL.

BACKGROUND: To compare the anterior surface roughness of two commercially available posterior chamber phakic intraocular lenses (IOLs) using atomic force microscopy (AFM). METHODS: Four phakic IOLs were used for this prospective, experimental study: two Visian ICL EVO+ V5 lenses and two iPCL 2.0 lenses. All of them were brand new, were not previously implanted in humans, were monofocal and had a dioptric power of - 12 diopters (D). The anterior surface roughness was assessed using a JPK NanoWizard II® atomic force microscope in contact mode immersed in liquid. Olympus OMCL-RC800PSA commercial silicon nitride cantilever tips were used. Anterior surface roughness measurements were made in 7 areas of 10 × 10 µm at 512 × 512 point resolution. The roughness was measured using the root-mean-square (RMS) value within the given regions. RESULTS: The mean of all anterior surface roughness measurements was 6.09 ± 1.33 nm (nm) in the Visian ICL EVO+ V5 and 3.49 ± 0.41 nm in the iPCL 2.0 (p = 0.001). CONCLUSION: In the current study, we found a statistically significant smoother anterior surface in the iPCL 2.0 phakic intraocular lenses compared with the VISIAN ICL EVO+ V5 lenses when studied with atomic force microscopy.

Effect of Laser-assisted Subepithelial Keratectomy with Mitomycin C on Corneal Optical Density Measured with Confocal Microscopy.

SIGNIFICANCE: The development of confocal microscopy allows one to obtain high-resolution corneal images like its optical density. Some studies have evaluated the optical density with Scheimpflug cameras in the early post-operative period after photorefractive keratectomy, but no studies have evaluated the long-term evolution of optical density after surface ablation when mitomycin C is used. PURPOSE: This work aimed to study the changes in corneal optical density measured with confocal microscopy in eyes treated with laser-assisted subepithelial keratectomy (LASEK) and intraoperative mitomycin C (MMC) to correct myopia. METHODS: A study of 24 consecutive myopic eyes that underwent LASEK with 0.02% MMC and a control group of 24 healthy nontreated eyes was performed. Optical density was measured using the images by the confocal microscopy of the Heidelberg Retina Tomograph II with the Rostock Cornea Module. An analysis of confocal microscopy images was performed using the ImageJ software to obtain the optical density, in gray-scale units (GSU). The optical density of the stromal bed was evaluated 3 months, 15 months, and 3 years after surgery and was compared with the optical density at the equivalent depth of the stroma in controls. RESULTS: The mean values of optical density for the LASEK group were 81.7 ± 9.7, 78.6 ± 11.7, and 73.6 ± 18.7 GSU at 3 months, 15 months, and 3 years, respectively, and it was 61.8 ± 8.2 GSU for the control group. A statistically higher optical density 3 and 15 months after LASEK with MMC was found compared with controls (P < .001). No significant difference was found in optical density at 3 years post-operatively. CONCLUSIONS: Our study suggests that, after LASEK with MMC, the anterior corneal stroma has a higher optical density at 3 and 15 months post-operatively, which gradually returns to normal values 3 years after surgery.

Analysis of corneal stromal roughness after iFS 150 kHz and LenSx femtosecond LASIK flap creation in porcine eyes.

PURPOSE: To describe and compare the stromal bed roughness obtained after laser in situ keratomileusis (LASIK) flap creation using a corneal femtosecond laser platform (iFS 150) and a "dual" femtosecond (FS) laser platform (LenSx). METHODS: This ex vivo experimental study was conducted in an animal model using 12 freshly enucleated porcine eyes, six with each femtosecond laser. The standard laser treatment parameters were used for the experiment. After LASIK flap creation, the corneal stromal roughness was assessed using atomic force microscopy (AFM) in contact mode immersed in liquid. In each sample, surface measurements were obtained in 60 regions of six eyes per FS laser in 10 20 × 20-micron areas of the central corneal stroma at 512 × 512-point resolution. The surface roughness was measured and the root-mean-square (RMS) values of the roughness were obtained. RESULTS: The mean RMS ± standard deviation values were 430 ± 150 nm for the corneal femtosecond laser platform and 370 ± 100 nm for the dual FS laser platform (P < 0.011). CONCLUSIONS: In this experimental study with AFM, we found smoother stromal beds after LASIK flap creation with LenSx compared to iFS 150 kHz. Further studies are needed to understand visual implications of the differences found.

Development of an effective and rapid qPCR for identifying human ChREBPα/ß isoforms in hepatic and adipose tissues.

Most quantitative real-time PCR (qPCR) detection methods use two types of chemistries to measure the expression levels of ChREBP isoforms, hydrolysis probes for ChREBPα and SYBR Green for ChREBPß. Hydrolysis probes are not available to determine the ChREBPß isoform. The aim of this study was to develop a qPCR assay based only on hydrolysis probes for both ChREBP isoforms. Liver and adipose tissue biopsies from patients undergoing elective cholecystectomy surgery were used to perform qPCR. To validate this assay, the results were compared with sequencing and High Resolution Melting (HRM) PCR assays. Direct sequencing was used to determine the sequence showing site where ChREBPß presents its specific splicing (1 b exon/2 exon) in order to design the primers and the probe. We developed a qPCR assay to determine the ChREBP isoforms expression based on hydrolysis probes. It assays showed good efficiency (95.50%, on average), high reproducibility, and a strong linear correlation (R2 ≥ 0.99) for tissues tested. HRM analysis confirmed the specificity of the primers and the result of this assay matched (100%) with the outcomes obtained by sequencing and qPCR. Also, we obtained the ChREBPß sequence showing exon 1b spliced to exon 2, bypassing exon 1a, and retaining the remainder of the ChREBPα exons. Based on the use of hydrolysis probes, our method can efficiently identify the expression of both ChREBP isoforms. Thus, the comparability of the qPCR results using a single chemistry (hydrolysis probes) to discriminate between both ChREBP isoforms was possible.

Myopic Laser-Assisted Subepithelial Keratectomy (LASEK) outcomes using three different excimer laser platforms: a retrospective observational study.

BACKGROUND: To compare the visual and refractive outcomes after myopic LASEK using three different excimer lasers and standardized surgical and mitomycin C (MMC) application protocols. METHODS: In this retrospective, observational cohort study, we examined 122 eyes treated with Allegretto, 135 eyes treated with Esiris and 137 eyes treated with Technolas excimer lasers. All eyes were treated under the same surgical protocol, and a standardized MMC dosage was used. The three groups were refraction-matched, and both visual and refractive outcomes were evaluated at 1 and 7 days and 1 and 3 months after surgery. RESULTS: At 3 months postsurgery, Allegretto provided significantly better outcomes than Esiris and Technolas in terms of postoperative uncorrected distance visual acuity (UDVA) (1.11 ± 0.2 vs 1.01 ± 0.2 vs 0.98 ± 0.2) (P = 0.0001), corrected distance visual acuity (CDVA) (1.13 ± 0.2 vs 1.10 ± 0.1 vs 1.04 ± 0.2) (P = 0.0001), residual sphere (- 0.01 ± 0.2 vs + 0.29 ± 0.7 vs + 0.27 ± 0.6) (P = 0.0001), and efficacy index (0.99 ± 0.2 vs 0.90 ± 0.2 vs 0.91 ± 0.2) (P = 0.0004). CONCLUSIONS: We found slightly better visual and refractive outcomes in the Allegretto group at 3 months post-op after LASEK with MMC to correct myopia.

CARMA1- and MyD88-dependent activation of Jun/ATF-type AP-1 complexes is a hallmark of ABC diffuse large B-cell lymphomas.

A hallmark of the diffuse large B-cell lymphoma (DLBCL) of the activated B-cell (ABC) type, a molecular subtype characterized by adverse outcome, is constitutive activation of the transcription factor nuclear factor-κB (NF-κB), which controls expression of genes promoting cellular survival and proliferation. Much less, however, is known about the role of the transcription factor activator protein-1 (AP-1) in ABC DLBCL. Here, we show that AP-1, like NF-κB, was controlled by constitutive activation of the B-cell receptor signaling component caspase recruitment domain-containing membrane-associated guanylate kinase 1 (CARMA1) and/or the Toll-like receptor signaling component myeloid differentiation primary response gene 88 (MyD88) in ABC DLBCL cell lines. In contrast to germinal center (GC) B-cell (GCB) DLBCL, ABC DLBCL cell lines expressed high levels of the AP-1 family members c-Jun, JunB, and JunD, which formed heterodimeric complexes with the AP-1 family members activating transcription factor (ATF) 2, ATF3, and ATF7. Inhibition of these complexes by a dominant-negative approach led to impaired growth of a majority of ABC DLBCL cell lines. Individual silencing of c-Jun, ATF2, or ATF3 decreased cellular survival and revealed c-Jun/ATF2-dependent control of ATF3 expression. As a consequence, ATF3 expression was much higher in ABC vs GCB DLBCL cell lines. Samples derived from DLBCL patients showed a clear trend toward high and nuclear ATF3 expression in nodal DLBCL of the non-GC or ABC subtype. These findings identify the activation of AP-1 complexes of the Jun/ATF-type as an important element controlling the growth of ABC DLBCL.

Immunomodulatory Effects of the Nutraceutical Garlic Derivative Allicin in the Progression of Diabetic Nephropathy.

Diabetic nephropathy (DN) is presently the primary cause of chronic kidney disease and end-stage renal disease (ESRD). It has been suggested that inflammation and oxidative stress, in addition to or in concert with the metabolic changes, plays an important role in the maintenance and progression of the disease. Therefore, attenuating or blocking these mechanisms may be a therapeutic target to delay the progression of the disease. Diallyl thiosulfinate (allicin), a compound derived from garlic, inhibits free radical formation, increases glutathione synthesis and decreases the levels of proinflammatory molecules in vitro. This research aimed to assess the effect of allicin on oxidative stress and inflammation-induced diabetes. Animals were divided into control and diabetes (streptozotocin 50 mg/kg i.p.), and maintained for 30 days. After 30 days, the group of diabetic animals was subdivided into diabetes and allicin-treated diabetes (16 mg/kg/day oral gavage). The three experimental groups were maintained for another month. We analyzed the status of renal function, oxidative stress and proinflammatory cytokines. The untreated diabetic group showed hyperglycemia and increased diuresis, creatinine clearance, proteinuria, glycosuria and urinary excretion of N-acetyl-ß-d-glucosaminidase (NAG), as well as increased oxidative stress and the expression of interleukin 1ß (IL-1ß), IL-6, nuclear factor kappa beta (NFκß) and transforming growth factor-ß1 (TGF-ß1) in plasma and kidney. In contrast, the inhibitor of NFκß (Iκß) is decreased in the cortex. It has been demonstrated that the allicin treatment decreases hyperglycemia, polyuria, and NAG excretion. The oxidative stress and proinflammatory cytokines were also reduced by the allicin treatment. In conclusion, allicin delays the progression of diabetic nephropathy through antioxidant and anti-inflammatory mechanisms.

[CLINICAL CASES-TREATED WITH TECHNOLOGY LIPID COLLOIDAL (TLC)]. / Casos clinicos tratados con La tecnologia lipido coloidal (TLC).

INTRODUCTION: This study presents clinical cases collecting etiologies that are more frequent in the field of complex wounds. All require a specific approach, as well as the interdisciplinary participation of different members of the team. But in general, established local cure plans may be quite similar. Applies them technology lipid colloidal (TLC) which consists of the combination of particles of hydrocolloid (carboxymethylcellulose) with lipid components. Products with a technology designed for every moment of healing. OBJECTIVE: Show our experience in the use of products with TLC in patients with ulcers of different etiologies. METHOD: The following products depending on the case have been used to treat: UrgoTul Absorb Border, Urgoclean (rope or plate), UrgoStart, UrgoK2 and UrgoK2 LITE. These products were applied in patients presenting four different etiologies of ulcer: hypertensive, traumatic, venous and ischemic ulcer. The use of Urgoclean rope favored cleaning the bed ulceral and applied Urgoclean plate with reinforced alginate to control the abundant exudates, with coverage of UrgoTul ABsorb Border. Once clean beds pass UrgoStart and at all times UrgoK2 bandage, cases that required compressive therapy. Intolerance to that kind of compression applied to patients presenting bandage UrgoK2 LITE (which tolerated without problem) which significantly reduced edema, favoring the control of exudate. Patients with ulcer of long evolution, at the start were reluctant to the application of new technologies, but after the first cures and sensing a good evolution, we get their confidence and commitment to the resolution. RESULTS: Are displayed clinical cases of different etiologic and personal contexts that an integral and interdisciplinary approach together with the application of products with TLC, managed to solve the problem. CONCLUSION: The materials used have been satisfactory in all cases, with a direct involvement in the resolution of lesions which carries a long unresolved, and in any of them, even with a diagnosis of poor prognosis. In the clinical practice of the wound care knowledge and research of new materials that improve the quality of life of patients, reducing the time evolution of the lesions is very important. Not to mention that education for the prevention of their health should be one of the objectives to prevent recurrences.

PD1 inhibits PKCθ-dependent phosphorylation of cytoskeleton-related proteins and immune synapse formation.

ABSTRACT: The inhibitory surface receptor programmed cell death protein 1 (PD1) is a major target for antibody-based cancer immunotherapies. Nevertheless, a substantial number of patients fail to respond to the treatment or experience adverse effects. An improved understanding of intracellular pathways targeted by PD1 is thus needed to develop better predictive and prognostic biomarkers. Here, via unbiased phosphoproteome analysis of primary human T cells, we demonstrate that PD1 triggering inhibited the phosphorylation and physical association with protein kinase Cθ (PKCθ) of a variety of cytoskeleton-related proteins. PD1 blocked activation and recruitment of PKCθ to the forming immune synapse (IS) in a Src homology-2 domain-containing phosphatase-1/2 (SHP1/SHP2)-dependent manner. Consequently, PD1 engagement led to impaired synaptic phosphorylation of cytoskeleton-related proteins and formation of smaller IS. T-cell receptor induced phosphorylation of the PKCθ substrate and binding partner vimentin was long-lasting and it could be durably inhibited by PD1 triggering. Vimentin phosphorylation in intratumoral T cells also inversely correlated with the levels of the PD1 ligand, PDL1, in human lung carcinoma. Thus, PKCθ and its substrate vimentin represent important targets of PD1-mediated T-cell inhibition, and low levels of vimentin phosphorylation may serve as a biomarker for the activation of the PD1 pathway.

Creation of a new femtosecond laser-assisted mini-flap to enhance late regression after LASIK.

PURPOSE: To describe a method of LASIK enhancement in which a new femtosecond laser-assisted mini-flap is created over the original LASIK flap. METHODS: The 60-kHz IntraLase femtosecond laser (IntraLase Corp., Irvine, CA) was used to create a new mini-flap over an original LASIK flap for the re-treatment of late regression after LASIK. The diameter of the mini-flap was 7 mm and the attempted flap depth was 100 µm. RESULTS: The procedure was performed on 10 eyes of 7 patients. No intraoperative or postoperative complications developed in any case during the follow-up. At the 6-month follow-up visit, all eyes were within ±0.5 diopters of the targeted refraction. CONCLUSIONS: The preliminary results suggest that creation of a femtosecond laser-assisted mini-flap over a previous LASIK flap seems to be a safe and effective procedure for the enhancement of late regression after LASIK. By creating a femtosecond laser-assisted mini-flap that is smaller in diameter than the original flap, the adhesion of the primary flap edges and peripheral interface remain intact, thus decreasing the risk of dislocation of the original LASIK flap and of losing a sliver of tissue.

[Epidemiology and clinical features of Streptococcus pyogenes bacteremia in Cartagena (Murcia, Spain)]. / Epidemiología y características clínicas de los episodios de bacteriemia por Streptococcus pyogenes en Cartagena (Murcia).

INTRODUCTION: A gradual increase in severe cases due to Streptococcus pyogenes or Streptococcus beta-hemolytic group A (SGA), has been detected in the last few decades. METHODS: Retrospective study of bacteremia due to S.pyogenes detected between January 2009 and January 2013 in Cartagena. The annual incidence for severe bacteremia has been estimated. RESULTS: Thirteen cases of SGA bacteremia were recorded. The incidence increased from 0.37 in 2009 to 2.5 cases/100,000 inhabitants in 2012. The predominant focus was skin and soft tissue infections (53%). Early mortality was 20%. CONCLUSION: Severe streptococcal disease is rare, but affects individuals with good functional status, and is associated with a high mortality.

PPAR-γ Agonist GW1929 Targeted to Macrophages with Dendrimer-Graphene Nanostars Reduces Liver Fibrosis and Inflammation.

Macrophages play essential roles during the progression of chronic liver disease. They actively participate in the response to liver damage and in the balance between fibrogenesis and regression. The activation of the PPARγ nuclear receptor in macrophages has traditionally been associated with an anti-inflammatory phenotype. However, there are no PPARγ agonists with high selectivity for macrophages, and the use of full agonists is generally discouraged due to severe side effects. We designed dendrimer-graphene nanostars linked to a low dose of the GW1929 PPARγ agonist (DGNS-GW) for the selective activation of PPARγ in macrophages in fibrotic livers. DGNS-GW preferentially accumulated in inflammatory macrophages in vitro and attenuated macrophage pro-inflammatory phenotype. The treatment with DGNS-GW in fibrotic mice efficiently activated liver PPARγ signaling and promoted a macrophage switch from pro-inflammatory M1 to anti-inflammatory M2 phenotype. The reduction of hepatic inflammation was associated with a significant reduction in hepatic fibrosis but did not alter liver function or hepatic stellate cell activation. The therapeutic antifibrotic utility of DGNS-GW was attributed to an increased expression of hepatic metalloproteinases that allowed extracellular matrix remodeling. In conclusion, the selective activation of PPARγ in hepatic macrophages with DGNS-GW significantly reduced hepatic inflammation and stimulated extracellular matrix remodeling in experimental liver fibrosis.

Distribution of three SNPs related to low bone mineral density in Amerindian groups and Mestizos from Mexico.

OBJECTIVES: Some Single nucleotide polymorphisms (SNPs) of several candidate genes have been associated with low bone mineral density (BMD) and fracture risk. As the genetic variability of such SNPs in Hispanic and Native American populations is scarce, we analyzed the three SNPs that have been related with bone mass disorders (Sp1, A163G, and BsmI) located in the genes of Type I Collagen (COL1A1), Osteoprotegerin (OPG), and Vitamin D receptor (VDR) in Mexican Mestizos (people resulting from post-Columbian admixture) and five Amerindian populations. METHODS: We genotyped these three SNPs by Polymerase chain reaction (PCR) and Restriction fragment length polymorphisms (RFLPs) in 523 individuals from five Mexican Amerindian groups (Nahua, Maya, Purépecha, Tarahumara, and Huichol) and 227 western Mestizos (Jalisco state). RESULTS: The modal allele was the same in all the six populations for Sp1-COL1A1 (S > 77%), A163G-OPG (A > 80%), and BsmI-VDR (b > 62%). Genotype distribution was in Hardy-Weinberg equilibrium in all SNPs/populations, excepting Sp1-COL1A1 in the Purépecha group and BsmI-VDR in Mestizo. In terms of the presumably Sp1-COL1A1 risk allele to low BMD (allele "s"), the Purépecha group showed the highest allele (23%) and homozygous (14.5%) frequencies. If the role of this allele as a genetic predisposing factor to low BMD were confirmed, this would mean increased susceptibility of Purépechas with regard to Europeans (14.5 vs. 6.8%). CONCLUSIONS: This finding presumably could influence the genetic susceptibility to low BMD in Purépechas. For the SNPs, BsmI-VDR and A163G-OPG, relative homogeneity was observed among the Mexican populations analyzed here.

Corneal Confocal Microscopy Findings in Neuro Lyme Disease: A Case Report.

Neuro Lyme disease is caused by several bacteriae of the Borreliaceae family, such as Borrelia Miyamotoi. In late stages of illness, patients with Lyme disease may develop chronic neurologic symptoms such as cognitive disturbances or small fiber peripheral neuropathy. Confocal microscopy is a non-invasive method designed to evaluate the human cornea in vivo. Thus, all the corneal layers, including the cells and the sub-basal nerve plexus, can be easily visualized and analyzed. This is the first report of the morphology of small-fiber peripheral neuropathy analyzed by confocal microscopy in a patient diagnosed of neuro Lyme disease. The decrease in the number of unmyelinated sub-basal nerve fibers with abundant presence of dendritic cells (DC) in comparison with healthy corneas strongly supports the diagnosis of small fiber peripheral neuropathy in a case of neuroborreliosis disease.

Impact of femtosecond laser-assisted in situ keratomileusis on retinal ganglion cell function.

PURPOSE: To analyse the effect of femtosecond laser-assisted in situ keratomileusis (FS-LASIK) on the electrical response of retinal ganglion cells using pattern electroretinography (pERG). METHODS: This was a longitudinal, prospective, observational pilot study. We included consecutive myopic patients who underwent FS-LASIK to correct up to 6 dioptres of myopia and up to 2 dioptres of astigmatism. Patients with excessive blinking or tearing and those with Snellen uncorrected visual acuity less than 0.9 dec on postop day 1 were excluded. Diopsys NOVA® (Diopsys Inc., NJ) pERG records, using high- and low-contrast patterns, were obtained 16 h and 1 month after FS-LASIK was performed. Magnitude (µV), Magnitude D (µV), Magnitude D/Magnitude ratio and signal-to-noise ratio (dB) were analysed. Wilcoxon test for nonparametric paired data was employed. RESULTS: pERG data from 24 eyes were analysed from 24 patients who underwent FS-LASIK. Mean age was 35.79 ± 9.86 years. Mean preoperative refraction was -2.69 ± 7.6 D (spherical) and -0.38 ± 0.40 D (cylinder). Mean surgical time was 56.88 ± 7.6 s. No statistically significant differences were obtained for any of the studied parameters when comparing 16 h with 1 month after FS-LASIK, with the exception of Magnitude with low contrast, which increased from 1.21 ± 0.2 to 1.39 ± 0.29 µV at 16 h and 1 month postoperatively, respectively (p = 0.03). CONCLUSIONS: FS-LASIK seems to induce a mild and transitory defect in retinal ganglion cell function. Only a mild decrease was detected in the magnitude value for low-contrast stimuli when pERG was performed 16 h postoperatively, and it returned to normal 1 month after surgery.