Bio-Guided Isolation of Acetogenins from Annona cherimola Deciduous Leaves: Production of Nanocarriers to Boost the Bioavailability Properties.

Annonaceous acetogenins (ACGs) are lipophilic polyketides isolated exclusively from Annonaceae. They are considered to be amongst the most potent antitumor compounds. Nevertheless, their applications are limited by their poor solubility. The isolation of ACGs from Annona cherimola leaves, an agricultural waste, has not been reported to date. Molvizarin (1) cherimolin-1 (2), motrilin (3), annonacin (4) and annonisin (5) are isolated for the first time from A. cherimola deciduous leaves. Annonacin was found to be four- and two-times more potent in tumoral cells (HeLa, 23.6% live cells; IGROV-1, 40.8% live cells for 24 h) than in HEK-293 at 50 µM (24 h, 87.2% live cells). Supramolecular polymer micelles (SMPMs) were synthesized to encapsulate the major ACG isolated, annonacin, in order to improve its solubility in aqueous media. The bioavailability of this compound was increased by a factor of 13 in a simulated human digestive system when compared with free annonacin and an encapsulation efficiency of 35% was achieved. In addition, the cytotoxic activity of SMPMs that hosted annonacin (100 µM, 24 h, 5.8% live cells) was increased compared with free annonacin in water (100 µM, 24 h, 92% live cells). These results highlight the use of by-products of A. cherimola, and their pure compounds, as a promising source of anticancer agents. The use of SMPMs as nanocarriers of ACGs could be an alternative for their application in food field as nutraceutical to enhance the administration and efficacy.

Reliability and reproducibility of a rodent model of choroidal neovascularization based on the subretinal injection of polyethylene glycol.

Purpose: To evaluate the reliability and reproducibility of a rodent choroidal neovascularization (CNV) model by subretinal injection of polyethylene glycol (PEG). Methods: C57BL/6 mice were injected subretinally with 2 µl PBS (Gibco, Invitrogen, Paisley, UK; n=14) or PEG (1 mg; n=18). Animals were sacrificed at either 0, 5, 14 or 21 days. Eyes were embedded in paraffin wax and serial sections were stained with haematoxylin and eosin or Fontana-Masson or immunostained for cytokeratin 8/18, isolectin B4 (IB4), vascular endothelial growth factor (VEGF) and von Willebrand factor (vWF). Results: Both the PBS and PEG groups had retinal degeneration and retinal pigment epithelium (RPE)/choroid modifications at 5 and 14 days. Pigment clumps and cell vacuolization at the RPE/choroid were identified as melanin-containing RPE cells. In PEG-injected eyes, CK8/18-positive cellular elements were present at the subretinal space, IB4 immunoreactivity was significantly increased and choroidal vessels appeared diffusely thickened. However, neither VEGF nor vWF (angiogenesis/neovascularization markers) were detected in either group. At 21 days, the retina/choroid of PBS-injected animals was normal in appearance, while retina/choroid changes remained in some PEG-injected mice. Conclusions: Subretinal injection of PEG induced retina/choroid degenerative modifications that mimic the initial steps of human CNV. However, ocular changes were heterogeneous among animals from PBS and PEG groups and did not follow a consistent pattern while most PBS-injected animals showed similar degenerative changes. Abnormal growth of new vessels originating from the choroidal vasculature was not observed. Therefore, we consider that this model does not consistently reproduce CNV and that researchers should choose other rodent models of CNV to avoid misinterpreting their results.

Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.

Through the paracrine effects of stem cells, including the secretion of neurotrophic, immunomodulatory, and anti-apoptotic factors, cell-based therapies offer a new all-encompassing approach to treatment of neurodegenerative diseases. In this study, we used physically separated co-cultures of porcine neuroretina (NR) and human mesenchymal stem cells (MSC) to evaluate the MSC paracrine neuroprotective effects on NR degeneration. NR explants were obtained from porcine eyes and cultured alone or co-cultured with commercially available MSCs from Valladolid (MSCV; Citospin S.L.; Valladolid, Spain), currently used for several approved treatments. Cultures were maintained for 72 h. MSC surface markers were evaluated before and after co-culture with NRs. Culture supernatants were collected and the concentration of brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), and glial-derived neurotrophic factor (GDNF) were determined by enzyme-linked immunosorbent assays. NR sections were stained by haematoxylin/eosin or immunostained for terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), glial fibrillary acidic protein, ß-tubulin III, and neuronal nuclei marker. NR morphology, morphometry, nuclei count, apoptosis rate, retinal ganglion cells, and glial cell activation were evaluated. Treatment effects were statistically analysed by parametric or non-parametric tests. The MSCs retained stem cell surface markers after co-culture with NR. BDNF and CNTF concentrations in NR-MSCV co-cultures were higher than other experimental conditions at 72 h (p < 0.05), but no GDNF was detected. NR general morphology, total thickness, and cell counts were broadly preserved in co-cultures, and the apoptosis rate determined by TUNEL assay was lower than for NR monocultures (all p < 0.05). Co-cultures with MSCV also protected retinal ganglion cells from degenerative changes and reduced reactive gliosis (both p < 0.05). In this in vitro model of spontaneous NR degeneration, the presence of co-cultured MSCs retarded neuroglial degeneration. This effect was associated with elevated concentrations of the neurotrophic factors BDNF and CNTF. Our data suggest that the paracrine secretion of these, and possibly other molecules, are a potential resource for the treatment of several neuroretinal diseases.

Cross transfer acute effects of foam rolling with vibration on ankle dorsiflexion range of motion.

INTRODUCTION: Foam roller is a device used as a massage intervention for rehabilitation and fitness performance. OBJECTIVE: To examine the effects on the ankle dorsiflexion mobility of the foam roller as well as the combination of foam roller and vibration applied to the ankle plantarflexors muscles, and to observe the possible cross-effect. METHODS: Thirty-eight undergraduate students participated in the study (19 males and 19 females). This study investigated. Three conditions (3 sets of 20 s) were performed in a randomized order (independent variables): 1) foam roller (Roller), 2) foam roller and vibration (Roller+VIB), and 3) no foam roller or vibration (Control). to determine whether of foam roller with or without vibration would benefit ankle dorsiflexion mobility. Ankle dorsiflexion ROM and plantar flexor were measured in both legs before and immediately after the treatment. RESULTS: A cross-effect was found in the non-stimulated leg. There was a significant effect on ankle mobility of Roller and Roller+VIB conditions (6% and 7%, p<0.001). CONCLUSION: Foam roller massage and vibration stimulus' foam roller massage increase ankle mobility producing a cross-effect.

Open Versus Endovascular Treatment for Patients with Post-Carotid Endarterectomy Restenosis: Early and Long-term Results.

BACKGROUND: The aim of this study is to assess and compare the short- and long-term results of carotid artery stenting (CAS) and redo surgery in patients with restenosis after carotid endarterectomy (CEA). METHODS: From January 1988 to December 2014, 44 consecutive patients were treated for carotid restenosis (CR): 23 redo-CEA (52.3%) and 21 CAS (47.7%). Data from these patients were prospectively collected in a dedicated database. Early results and 3-year end points were analyzed and compared between groups with χ2 test, Kaplan-Meier curves, and Breslow test. RESULTS: Demographic characteristics and comorbidity were similar in both groups, except for arterial hypertension and chronic renal insufficiency which were higher in the CAS group. CR was symptomatic in 7 patients in the redo-CEA group (30.4%) and 1 (4.8%) in CAS (P = 0.04). No differences were found in the time period between primary CEA and reintervention, critical carotid stenosis, or contralateral carotid occlusion. Median follow-up was 61.5 months. In the redo-CEA group, 1 patient (4.3%) had a perioperative transient ischemic attack and 3 (13%) experienced cranial nerve injury with complete regression at 30 days. No differences were found between groups in terms of early and long-term mortality, neurologic morbidity, and overall morbidity. The rate of secondary restenosis and freedom from reintervention was similar in both groups during follow-up. CONCLUSIONS: Both CAS and redo-CEA are suitable options for patients with CR. CAS might be the treatment of choice due to the risk of cranial nerve injuries in redo-CEA. When CAS is contraindicated, redo-CEA remains a safe and effective treatment option.

An exploratory study on the ability of manganese to supplement rotenone neurotoxicity in rats.

Parkinson's disease (PD) is a complex disorder, primarily of idiopathic origin, with environmental stressors like rotenone and manganese linked to its development. This study explores their potential interaction and resulting neurotoxicity, aiming to understand how environmental factors contribute to PD. In an eight-day experiment, male Wistar rats weighing 280-300 g were subjected to rotenone, manganese, or a combination of both. Various parameters were assessed, including body weight, behavior, serum markers, tissue damage, protein levels (tyrosine hydroxylase, Dopamine- and cAMP-regulated neuronal phosphoprotein -DARPP-32-, and α-synuclein), and mitochondrial function. Manganese heightened rotenone's impact on reducing food intake without causing kidney or liver dysfunction. However, the combined exposure intensified neurotoxicity, which was evident in augmented broken nuclei and decreased tyrosine hydroxylase and DARPP-32 levels in the striatum. While overall mitochondrial function was preserved, co-administration reduced complex IV activity in the midbrain and liver. In conclusion, our findings revealed a parallel toxic effect induced by rotenone and manganese. Notably, while these substances do not target the same dopaminergic regions, a notable escalation in toxicity is evident in the striatum, the brain region where their toxic effects converge. This study highlights the need for further exploration regarding the interaction of environmental factors and their possible impact on the etiology of PD.

Response of Bacillus velezensis 83 to interaction with Colletotrichum gloeosporioides resembles a Greek phalanx-style formation: A stress resistant phenotype with antibiosis capacity.

Plant growth-promoting rhizobacteria, such as Bacillus spp., establish beneficial associations with plants and may inhibit the growth of phytopathogenic fungi. However, these bacteria are subject to multiple biotic stimuli from their competitors, causing stress and modifying their development. This work is a study of an in vitro interaction between two model microorganisms of socioeconomic relevance, using population dynamics and transcriptomic approaches. Co-cultures of Bacillus velezensis 83 with the phytopathogenic fungus Colletotrichum gloeosporioides 09 were performed to evaluate the metabolic response of the bacteria under conditions of non-nutritional limitation. The bacterial response was associated with the induction of a stress-resistant phenotype, characterized by a lower specific growth rate, but with antimicrobial production capacity. About 12% of co-cultured B. velezensis 83 coding sequences were differentially expressed, including the up-regulation of the general stress response (sigB regulon), and the down-regulation of alternative carbon sources catabolism (glucose preference). Defense strategies in B. velezensis are a determining factor in order to preserve the long-term viability of its population. Mostly, the presence of the fungus does not affect the expression of antibiosis genes, except for those corresponding to surfactin/bacillomycin D production. Indeed, the up-regulation of antibiosis genes expression is associated with bacterial growth, regardless of the presence of the fungus. This behavior in B. velezensis 83 resembles the strategy used by the classical Greek phalanx formation: by sacrificing growth rate and metabolic versatility, resources can be redistributed to defense (stress resistant phenotype) while maintaining the attack (antibiosis capacity). The presented results are the first characterization of the molecular phenotype at the transcriptome level of a biological control agent under biotic stress caused by a phytopathogen without nutrient limitation.

The p53 codon 72 polymorphism (rs1042522) is associated with proliferative vitreoretinopathy: the Retina 4 Project.

PURPOSE: To compare the distribution of a p53 gene polymorphism among European subjects undergoing primary retinal detachment (RD) surgery in relation to the development of proliferative vitreoretinopathy (PVR). DESIGN: Case-controlled gene association study conducted as a component of the Retina 4 Project (a European multicenter study). PARTICIPANTS AND CONTROLS: Five hundred fifty DNA samples, 134 with PVR secondary to primary RD and 416 with RD without PVR. METHODS: The p53 codon 72 polymorphism (rs1042522) was analyzed using allele-specific primer polymerase chain reaction. Proportions of genotypes and the proline (Pro-P) homozygote groups between subsamples from different countries were analyzed in 2 phases. In the first, subsamples from Spain and Portugal were analyzed. After significant results were found, samples from the United Kingdom (UK) and The Netherlands were analyzed (second phase). Genotypic and allelic frequencies were compared between cases and controls in the global sample. MAIN OUTCOME MEASURES: Single significant associations with PVR. RESULTS: A significant difference (P<0.05, Fisher exact test) was observed regarding the p53 genotype frequencies at codon 72 between the PVR cases and the non-PVR controls in Spain and Portugal (phase I), but not in the UK or The Netherlands (phase II). Analysis of Pro homozygote carriers between cases and controls revealed differences in Spain (29.01-42.18 and 2.29-10.20, respectively), Portugal (10.49-29.50 and 1.35-8.89, respectively), and The Netherlands (16.49-31.70 and 4.51-15.09, respectively), but no differences in the UK (7.68-18.1 and 4.85-13.94, respectively). The odds ratio of Pro carriers from Spain and Portugal together was 8.12 (95% confidence interval [CI], 3.72-17.69; P<0.05), whereas the odds ratio of Pro carriers from the UK and The Netherlands was 2.12 (95% CI, 0.96-4.68; P = 0.07). All control samples were in Hardy-Weinberg equilibrium. Considering the entire sample, significant differences were found in genotype frequencies between cases (RR, 30.59%; RP, 43.28%; PP, 26.11% [R = Arg; P = Pro]) and controls (RR, 39.66%; RP, 52.64%; PP, 7.69%) and in Pro homozygote carriers between controls (Pro homozygote 95% CI, 18.67-33.52) and cases (Pro homozygote 95% CI, 5.1-10.2). CONCLUSIONS: Results indicate that the Pro variant of p53 codon 72 polymorphism is associated with a higher risk of PVR developing after a primary RD. Further studies are necessary to understand the role of this polymorphism in the development of PVR.

Rotenone-Induced Model of Parkinson's Disease: Beyond Mitochondrial Complex I Inhibition.

Parkinson's disease (PD) is usually diagnosed through motor symptoms that make the patient incapable of carrying out daily activities; however, numerous non-motor symptoms include olfactory disturbances, constipation, depression, excessive daytime sleepiness, and rapid eye movement at sleep; they begin years before motor symptoms. Therefore, several experimental models have been studied to reproduce several PD functional and neurochemical characteristics; however, no model mimics all the PD motor and non-motor symptoms to date, which becomes a limitation for PD study. It has become increasingly relevant to find ways to study the disease from its slowly progressive nature. The experimental models most frequently used to reproduce PD are based on administering toxic chemical compounds, which aim to imitate dopamine deficiency. The most used toxic compounds to model PD have been 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA), which inhibit the complex I of the electron transport chain but have some limitations. Another toxic compound that has drawn attention recently is rotenone, the classical inhibitor of mitochondrial complex I. Rotenone triggers the progressive death of dopaminergic neurons and α-synuclein inclusions formation in rats; also, rotenone induces microtubule destabilization. This review presents information about the experimental model of PD induced by rotenone, emphasizing its molecular characteristics beyond the inhibition of mitochondrial complex I.

[Social, clinical and psychosocial determinants associated with uncontrolled arterial hypertension in older adults. SABE Survey Colombia 2016]. / Determinantes sociales, clínicos y psicosociales asociados a hipertensión arterial no controlada en adultos mayores. Encuesta SABE Colombia 2016.

OBJECTIVE: To evaluate sociodemographic, clinical and psychosocial characteristics that are associated with uncontrolled arterial hypertension (HANC) in older adults in Colombia. METHODS: Secondary analysis of data from the National Survey of Health, Welfare and Aging (SABE Colombia 2016), in which men and women aged 60 years or older in the country who were not institutionalized were interviewed. The dependent variable was uncontrolled hypertension (HANC) (≥140/90mm Hg). The SABE survey surveyed 23694 older adults; 11264 had a diagnosis of arterial hypertension (HTA) and were taking antihypertensive medication. On the other hand, 5106 older adults, randomly selected, had their blood pressure taken. Participants previously diagnosed with HTA under medical management with antihypertensives and who had had their blood pressure taken at the same time were included, resulting in a sample of 2656 participants. Sociodemographic, clinical and psychosocial characteristics were evaluated. Univariate, bivariate, and multivariate analyzes with logistic regression were performed. RESULTS: One thousand one hundred eighty-eight (44.7%) participants presented HANC. A higher prevalence of HANC was observed in adults older than 74 years (OR 1.31; 95% CI 1.09-1.57) and lower prevalence in residents of urban areas (OR 0.55; 95% CI 0.42-0.71). CONCLUSIONS: Age over 74 years and living in a rural area were identified as variables associated with inadequate blood pressure control in non-institutionalized older adults in Colombia.

Histologic characterization and risk factors for persistent albuminuria in adolescents in a region of highly prevalent end-stage renal failure of unknown origin.

Background: End-stage renal failure of unknown origin (ESRD-UO) is a public health problem in Mexico and many regions of the world. The prevalence of ESRD-UO in Aguascalientes, Mexico, is one of the highest worldwide, particularly in adults between 20 and 40 years of age. Our aim was to screen adolescents for chronic kidney disease (CKD) to identify risk factors and histologically characterize adolescents with persistent albuminuria. Methods: This was a cross-sectional, observational and comparative study of adolescents in whom serum creatinine and the albumin:creatinine ratio (ACR) were determined when screening for CKD. A clinical evaluation and risk factor survey were conducted. Patients with an abnormal ACR (≥30 mg/g) or a low glomerular filtration rate (GFR) (≤75 mL/min/1.73 m2) were re-evaluated and a renal ultrasound (US) was obtained. A kidney biopsy was performed in patients with persistent albuminuria. Results: A total of 513 students were included; 19 had persistent albuminuria and 494 were controls. The prevalence of persistent albuminuria was 3.7% [95% confidence interval (CI) 2.1-5.3]. Only one patient had a decreased GFR. None of the patients with persistent albuminuria had anatomical abnormalities of the urinary tract by renal US. Patients with persistent albuminuria had a decreased total renal volume compared with the control group (150 versus 195 mL/m2; P < 0.01). Eighteen kidney biopsies were performed; 72% had glomerulomegaly and only one patient had mild fibrosis. Podocyte abnormalities were evident on electron microscopy, including partial fusion (100%), microvillous degeneration (80%) and increased organelles (60%). Risk factors for persistent albuminuria were: homestead proximity to maize crops, the use of pesticides at the father's workplace, a family history of CKD and blood pressure abnormalities. The body mass index and breastfeeding were protective factors. Conclusions: The prevalence of persistent albuminuria in adolescents in Aguascalientes is high and histologic compromise is characterized by podocyte injury in the absence of fibrosis. The renal volume of persistent albuminuria patients was decreased, suggesting oligonephronia. Exposure to environmental toxins such as pesticides, even prenatally, may be responsible for this pathological entity. Screening programs in adolescents by determining ACR are necessary in this setting.

Chronic Kidney Disease Risk Profile in Renal Donors in Aguascalientes, Mexico: A Retrospective Cohort Study.

BACKGROUND: In the last decade, kidney donation has been recognized as a risk factor for end-stage renal disease (ESRD). ESRD risk calculators have been recently perfected in North American populations. In Mexico, the rates of overweight, obesity, and diabetes mellitus (DM) are among the highest worldwide; nevertheless, most kidney transplants are obtained from living donors. This study aims to describe the risk profile for chronic kidney disease (CKD) development in kidney donors in a highly active transplant center in Central Mexico. METHODS: We conducted a retrospective, observational, descriptive cohort study of kidney donors followed at the Hospital Centenario Miguel Hidalgo (CHMH). We used the pretransplant CKD risk calculator at 15 years and over a lifetime (www.transplantmodels.com/esrdrisk). Aside from the calculator of kidney failure risk, we also used the calculator for postdonation CKD risk (www.transplantmodels.com/donesrd/). Factors associated with a glomerular filtration rate (GFR) <60 mL/min were evaluated by univariate and multivariate analysis. RESULTS: The study included 543 donors. The average follow-up period was 1.7 years (±2.7) with a median of 0.7 years (interquartile range, 0.2-2.1). The average predicted risk for ESRD development at 15 years was 0.08% (±0.1); 25.6% had a risk >0.1%, and only 1 patient had a risk >1%. The lifetime ESRD risk was 0.62% (±0.5); 15% had a risk >1%, and the greatest risk was 3.5%. The median of patients at risk of developing postdonation ESRD was 1 in 10,000 donors (0.6-1.5) at 5 years, 5.7 in 10,000 donors (3.5-8.8) at 10 years, 15 in 10,000 donors (9.1-23.2) at 15 years, and 31 in 10,000 donors (18.9-47.7) at 20 years. During the follow-up period, 52 patients developed a GFR of <60 mL/min. Both risk estimation formulas were significantly associated with a GFR of <60 mL/min. Among the individual factors, the GFR (hazard ratio 0.96, 95% confidence interval 0.94-0.97, P < .001) and the urinary albumin to creatinine ratio (hazard ratio 1.009, 95% confidence interval 1.005-1.01, P < .001) remained statistically significant. CONCLUSION: The risk of ESRD in kidney donors in Aguascalientes, Mexico, is similar to that described in the United States. Risk calculators are an indispensable decision-making tool to better understand kidney donors in our milieu.

Dexamethasone PLGA Microspheres for Sub-Tenon Administration: Influence of Sterilization and Tolerance Studies.

Many diseases affecting the posterior segment of the eye require repeated intravitreal injections with corticosteroids in chronic treatments. The periocular administration is a less invasive route attracting considerable attention for long-term therapies. In the present work, dexamethasone-loaded poly(lactic-co-glycolic) acid (PLGA) microspheres (Dx-MS) were prepared using the oil-in-water (O/W) emulsion solvent evaporation technique. MS were characterized in terms of mean particle size and particle size distribution, external morphology, polymer integrity, drug content, and in vitro release profiles. MS were sterilized by gamma irradiation (25 kGy), and dexamethasone release profiles from sterilized and non-sterilized microspheres were compared by means of the similarity factor (f2). The mechanism of drug release before and after irradiation exposure of Dx-MS was identified using appropriate mathematical models. Dexamethasone release was sustained in vitro for 9 weeks. The evaluation of the in vivo tolerance was carried out in rabbit eyes, which received a sub-Tenon injection of 5 mg of sterilized Dx-MS (20-53 µm size containing 165.6 ± 3.6 µg Dx/mg MS) equivalent to 828 µg of Dx. No detectable increase in intraocular pressure was reported, and clinical and histological analysis of the ocular tissues showed no adverse events up to 6 weeks after the administration. According to the data presented in this work, the sub-Tenon administration of Dx-MS could be a promising alternative to successive intravitreal injections for the treatment of chronic diseases of the back of the eye.

Transcriptomic and proteomic analyses of the venom and venom glands of Centruroides hirsutipalpus, a dangerous scorpion from Mexico.

Centruroides hirsutipalpus (Scorpiones: Buthidae) is related to the "striped scorpion" group inhabiting the western Pacific region of Mexico. Human accidents caused by this species are medically important due to the great number of people stung and the severity of the resulting intoxication. This communication reports an extensive venom characterization using high-throughput proteomic and Illumina transcriptomic sequencing performed with RNA purified from its venom glands. 2,553,529 reads were assembled into 44,579 transcripts. From these transcripts, 23,880 were successfully annoted using Trinotate. Using specialized databases and by performing bioinformatic searches, it was possible to identify 147 putative venom protein transcripts. These include α- and ß-type sodium channel toxins (NaScTx), potassium channel toxins (KScTx) (α-, ß-, δ-, γ- and λ-types), enzymes (metalloproteases, hyaluronidases, phospholipases, serine proteases, and monooxygenases), protease inhibitors, host defense peptides (HDPs) such as defensins, non-disulfide bridge peptides (NDBPs), anionic peptides, superfamily CAP proteins, insulin growth factor-binding proteins (IGFBPs), orphan peptides, and other venom components (La1 peptides). De novo tandem mass spectrometric sequencing of digested venom identificatied 50 peptides. The venom of C. hirsutipalpus contains the highest reported number (77) of transcripts encoding NaScTxs, which are the components responsible for human fatalities.

Human Mesenchymal Stem Cell Secretome Exhibits a Neuroprotective Effect over In Vitro Retinal Photoreceptor Degeneration.

Retinal photoreceptor degeneration occurs frequently in several neurodegenerative retinal diseases such as age-related macular degeneration, retinitis pigmentosa, or genetic retinal diseases related to the photoreceptors. Despite the impact on daily life and the social and economic consequences, there is no cure for these diseases. Considering this, cell-based therapy may be an optimal therapeutic option. This study evaluated the neuroprotective in vitro potential of a secretome of human bone marrow mesenchymal stem cells (MSCs) for retinal photoreceptors in vitro. We analyzed the photoreceptor morphologic changes and the paracrine factors secreted by human bone marrow MSCs in a physically separated co-culture with degenerated neuroretinas, using organotypic neuroretinal cultures. The results showed that the secretome of human bone marrow MSCs had a neuroprotective effect over the neuroretinal general organization and neuropreserved the photoreceptors from degeneration probably by secretion of neuroprotective proteins. The study of the expression of 1,000 proteins showed increased paracrine factors secreted by MSCs that could be crucial in the neuroprotective effect of the stem cell secretome over in vitro retinal degeneration. The current results reinforce the hypothesis that the paracrine effect of the human bone marrow MSCs may slow photoreceptor neurodegeneration and be a therapeutic option in retinal photoreceptor degenerative diseases.

Venom gland transcriptome from Heloderma horridum horridum by high-throughput sequencing.

Lizards of the Helodermatidae (Anguimorpha) family consist of at least two well recognized species: Heloderma horridum horridum and Heloderma suspectum suspectum. They contain specialized glands in their jaws that produce venomous secretions that causes envenoming symptoms to bitten animals. One way to study proteins from such secretions is by RNA-seq; a powerful molecular tool to characterize the transcriptome of such specialized gland, and its protein secretions. The total RNA from venom gland tissues of H. horridum horridum was extracted and a cDNA library was constructed and sequenced. Overall, 114,172 transcripts were found, and 199 were annotated based on sequence similarities to previously described peptides/proteins. Transcripts coding for putative exendins, defensins, natriuretics and serine protease inhibitors were the most highly expressed. Transcripts that code for several putative serine proteases, phospholipases, metalloproteases, lipases, L-amino oxidase and nucleases were also found. Some of the novel identified transcripts were translationally controlled tumor proteins, venom factors, vespryns, waprins, lectins, cystatins and serine protease inhibitors. All these new protein structures may contribute to a better understanding of the venomous secretions of the Helodermatidae family.

Nontuberculous mycobacterial infection in a tertiary care center in Mexico, 2001-2017.

INTRODUCTION: Nontuberculous mycobacteria (NTM) comprise several pathogens with a complex profile of virulence, diverse epidemiological and clinical patterns as well as host specificity. Recently, an increase in the number of NTM infections has been observed; therefore, the objective of this study was to evaluate the clinical characteristics and outcomes of these infections. METHODS: We included patients with NTM infections between 2001-2017 and obtained risk factors, clinical features and outcomes; finally, we compared this data between slowly growing (SGM) and rapidly growing mycobacteria (RGM). RESULTS: A total of 230 patients were evaluated, 158 (69%) infected and 72 (31%) colonized/pseudoinfected. The average annual incidence in the first 11 years of the study was 0.5 cases per 1000 admissions and increased to 2.0 cases per 1000 admissions later on. The distribution of NTM infections was as follows: bloodstream and disseminated disease 72 (45%), lung infection 67 (42%), skin and soft tissue infection 19 (12%). Mycobacterium avium complex was the most common isolate within SGM infections, and HIV-infected patients were the most affected. Within RGM infections, M. fortuitum was the most common isolate from patients with underlying conditions such as cancer, type-2 diabetes mellitus, presence of invasive devices, and use of immunosuppressive therapy. We did not find significant differences in deaths and persistent infections between disseminated SGM infection when compared to disseminated RGM infection (42% vs. 24%, p=0.22). However, disseminated SGM infection required a longer duration of therapy than disseminated RGM infection (median, 210 vs. 42 days, p=0.01). NTM lung disease showed no significant differences in outcomes among treated versus non-treated patients (p=0.27). CONCLUSIONS: Our results show a significant increase in the number of Non-tuberculosis-mycobacteria infections in our setting. Patients with slow-growing-mycobacteria infections were mainly persons living with human immunodeficiency virus . Older patients with chronic diseases were common among those with rapidly-growing-mycobacteria infections. For non-tuberculosis-mycobacteria lung infection, antibiotic therapy should be carefully individualized.

Cultural adaptation and validation of the Geriatric Oral Health Assessment Index - GOHAI - Colombian version.

OBJECTIVE: This study aims to carry out the cultural adaptation and the validation of the GOHAI scale for the Colombian population. METHODS: Translation process, cultural adaptation, and content and face validity were carried out with a sample of 63 participants as a pretest. The validation counted with a sample of 7,200 subjects, divided into two groups: a work sample (WS) with 3,628 subjects and a confirmatory sample (CS) with 3,572 subjects. Construct, criterion validity and internal consistency were performed for both samples. Test-retest reliability was assessed with a sub-sample of 75 participants. RESULTS: The GOHAI showed an appropriate face and content validity, the pre-test revealed an understandable questionnaire, the scale showed a unidimensional factorial structure and a Cronbach's Alpha of 0.8. Convergent validity with a self-perception on general health scale pointed to a significant correlation (p= 0.0001), while discriminant validity showed significant differences regarding groups according to age group, skin color, educational level, socio-economic level, healthcare affiliation and self-perception about need of dental prostheses. Gender groups did not show significant differences among groups within either sample. The CS showed similar results, differences existed among factorial structures of 2 and 3 factors, and for discriminant validity, the CS showed statistically significant differences for the Area variable not in the WS. Kendall's test-retest analysis's correlation is 0.85 (p= 0.0000). CONCLUSIONS: The GOHAI scale is valid and reliable enough to be used as a measure of Oral-Health-Related Quality of Life in the Colombian elderly population, also could be applied for other Latin-American populations.

OBJETIVO: Adaptar culturalmente y validar la escala de autopercepción de salud bucal - Geriatric Oral Health Assessment Index (GOHAI) para la población mayor colombiana. MÉTODOS: El proceso de traducción, adaptación cultural, contenido y validez aparente se llevaron a cabo en el pre-test con una muestra de 63 participantes. La validación contó con una muestra de 7,200 sujetos, divididos en dos grupos: una muestra de trabajo (WS) con 3,628 sujetos y una muestra confirmatoria (CS) con 3,572 sujetos. Se realizó validez de constructo, criterio y consistencia interna para ambas muestras. La confiabilidad test-re-test se evaluó con una submuestra de 75 participantes. RESULTADOS: La escala GOHAI mostró condiciones adecuadas de apariencia y contenido, El pre-test mostro un cuestionario entendible y adecuado, la escala arrojo una estructura factorial única y una consistencia interna Alfa de Cronbach de 0,8. La validez convergente con la variable autopercepción en salud general mostró diferencia significativa entre grupos (p= 0.0001), la validez discriminante mostro diferencias significativas con las variables grupo de edad, color de piel, nivel educativo, estrato socio-económico, regímenes de salud y autopercepción de necesidad de prótesis dental; la variable Área mostró diferencia significativa en la MC, no en la muestra MT. El análisis test-retest mostro una correlación de Kendall de 0.85 (p= 0.0000). CONCLUSIÓN: El instrumento GOHAI es válido y confiable y puede ser usado como una medida de Calidad de Vida relacionada con Salud Bucal en personas mayores en Colombia y puede ser aplicado en otras poblaciones de habla hispana de América Latina.

[Conceptualization of institutional elderly caregiver in Colombia]. / Conceptualización de cuidador institucional de persona mayor en Colombia.

OBJECTIVE: To conceptualize institutional elderly caregiver in Colombia as formal caregivers. METHODS: A documentary review was carried out using a qualitative and descriptive approach, in order to analyze the work of institutional caregivers based on two dimensions: the internal dimension to realize their reality according to the study entitled "Institutional Caregiver: characterization, current situation and support networks - Colombia 2013", and the external dimension to recognize the perspective of the State and the academy on the issue. RESULTS: It was possible to see that, although Colombia has made progress on regulation matters, the country has not yet fully developed a care system for the elderly that articulates actors and responsibilities of care providers (individuals, families, civil society and the State). CONCLUSIONS: Elements are provided to understand institutional care and establish specific care training, the formal link between a care delivery institution and the surveillance-control scheme to conceptualize institutional elderly caregivers in Colombia as formal caregivers and thus fulfill some State and society goals.

OBJETIVO: Conceptualizar el cuidador institucional de persona mayor en Colombia como cuidador formal. METODOLOGÍA: Se realizó una revisión documental desde un enfoque cualitativo, descriptivo para analizar la labor del cuidador institucional en dos dimensiones: Interna para reconocer la realidad según el estudio "Cuidador Institucional: caracterización, situación actual y redes de apoyo - Colombia 2013 y la Externa para reconocer la mirada del Estado y de la Academia. RESULTADOS: Permitieron argumentar que si bien Colombia ha avanzado normativamente, aun no desarrolla completamente un sistema de cuidado para personas mayores que articule actores y responsabilidades de los proveedores de cuidado (individuo, familia, sociedad civil y Estado). CONCLUSIONES: Se aportan elementos para comprender el cuidado institucional y para establecer la formación específica en cuidado, la vinculación formal con la institución de cuidado y el esquema de vigilancia - control como conceptualización del cuidador institucional de la persona mayor en Colombia como Cuidador Formal y así dar cumplimiento de algunas metas estatales y de la sociedad colombiana.