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Objectives: This study aimed to evaluate gender-based disparities in preventable adverse events due to low-value practices (LVPs) in primary care. Methods: A retrospective cohort study in Alicante, Spain. Results: A total of 1,516 patient records were examined, finding that older individuals and women experienced more LVP-related events. Female patients faced a higher volume of such events than males with the same health issue. Interaction analysis revealed patients treated by male physicians had more severe events, while those attended by females experienced milder ones. Adverse events were more frequent in LVPs associated with gender-based reasons. Conclusion: These results highlight the need for tailored healthcare professional awareness programs on overuse's impact on safety. Addressing outcome differences between male and female patients should inform awareness campaigns.
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Medicina de Família e Comunidade , Humanos , Espanha , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Adulto , Idoso , Atenção Primária à Saúde , Disparidades em Assistência à SaúdeRESUMO
PURPOSE: This study aimed to evaluate the efficacy, safety, and participant compliance of orthokeratology treatment for the correction of myopic refractive errors over a six-month prospective study and to define the potential reasons for early treatment discontinuation. METHODS: A total of 32 participants with low-to-moderate myopia were fitted with the spherical model of corneal refractive therapy (CRT) orthokeratology lenses (Paragon Vision Sciences) and followed over six months, with specific attention to alterations in refractive error, corneal topography, and epithelial thickness. Concurrently, participant feedback and reasons for any treatment discontinuation were documented. RESULTS: Significant changes in refractive error and in corneal topography were observed, with approximately 50% of the refractive error being corrected on the first night of use and 100% by the first two weeks (P<0.001). Central epithelial thickness experienced substantial thinning, reducing to 15.65±4.49 µm (67.38%) (P<0.001) after 6 months of lens use. Six participants withdrew from this study for varied reasons, including unmet visual expectations and difficulty adhering to the lens-wearing regimen. Notably, the dropout group exhibited higher baseline low-order aberrations and less prolate corneas than those who persisted with the treatment (P<0.05). CONCLUSION: Orthokeratology with CRT is efficacious and safe for the correction of low-to-moderate myopia in adults, but a portion of patients discontinue the treatment in the first 6 months of contact lens wear. Special care should be taken when recommending orthokeratology in patients with higher levels of myopia and corneas with less prolate shape, providing more realistic expectations and even changing to dual axis or more sophisticated designs.
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BACKGROUND: Data on overuse of diagnostic and therapeutic resources underline their contribution to the decline in healthcare quality. The application of "Do Not Do" recommendations, in interaction with gender biases in primary care, remains to be fully understood. Therefore, this study aims to identify which low-value practices (LVPs) causing adverse events are susceptible to be applied in primary care setting with different frequency between men and women. METHODS: A consensus study was conducted between November 1, 2021, and July 4, 2022, in the primary care setting of the Valencian Community, Spain. Thirty-three of the 61 (54.1%) health professionals from clinical and research settings invited, completed the questionnaire. Participants were recruited by snowball sampling through two scientific societies, meeting specific inclusion criteria: over 10 years of professional experience and a minimum of 7 years focused on health studies from a gender perspective. An initial round using a questionnaire comprising 40 LVPs to assess consensus on their frequency in primary care, potential to cause serious adverse events, and different frequency between men and women possibly due to gender bias. A second round-questionnaire was administered to confirm the final selection of LVPs. RESULTS: This study identified nineteen LVPs potentially linked to serious adverse events with varying frequencies between men and women in primary care. Among the most gender-biased and harmful LVPs were the use of benzodiazepines for insomnia, delirium, and agitation in the elderly, and the use of hypnotics without a previous etiological diagnosis. CONCLUSIONS: Identifying specific practices with potential gender biases, mainly in mental health for the elderly, contributes to healthcare promotion and bridges the gap in gender inequalities. TRIAL REGISTRATION: NCT05233852, registered on 10 February 2022.
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Atenção Primária à Saúde , Sexismo , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Uso Excessivo dos Serviços de Saúde/prevenção & controle , Uso Excessivo dos Serviços de Saúde/estatística & dados numéricos , Qualidade da Assistência à Saúde , Espanha/epidemiologia , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To identify strengths, obstacles, changes in the environment, and capabilities of primary care teams and support units, with the aim of providing high-quality care in an integrated healthcare area. DESIGN: Mixed methods study based on the SWOT matrix and CAME analysis. LOCATION: Primary care, Valencian community. PARTICIPANTS: A total of 271 professionals from different collectives and patient association representatives participated. 99 in the idea generation phase, 154 in the SWOT matrix development phase, and 18 in the CAME analysis development phase. INTERVENTIONS: A SWOT-CAME analysis was conducted, from which action lines were established. Information capture was carried out through nominal groups, and the consensus phase involved integrating all professionals through Delphi and consensus conference techniques. MAIN MEASUREMENTS: Prioritization of proposals to maintain strengths, address threats, exploit opportunities, and correct weaknesses within the framework of an integrated healthcare area action plan. RESULTS: A total of 82 different ideas were proposed (20 strengths; 40 weaknesses; 4 threats; 12 opportunities; 6 threats-opportunities), which, once prioritized, were translated into 7 lines and 33 prioritized actions/interventions (CAME analysis). CONCLUSIONS: Integrated care, seeking collaborative approaches between care levels, redefining roles, digital solutions, staff training, and improvements in equipment and support processes, along with measures to address the aging population and the needs of socio-sanitary centers, constitute the challenges to be addressed.
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Envelhecimento , Instalações de Saúde , Porfirinas , Humanos , Idoso , Consenso , Atenção Primária à SaúdeRESUMO
This study aims to assess the inclusion of second victims and other patient safety issues in the curricula of undergraduate medical and nursing degrees in the countries participating in the European Researchers' Network Working on Second Victims (The ERSNT Consortium, COST Action 19,113). A review of medical and nursing school curricula in 206 universities was carried out, using their websites to search for subjects addressing "patient safety", "quality of care", "risk management", "safe practices", "interprofessional communication", "adverse events", and "second victims". There was substantial variability in the extent of training for patient safety. Forty-four out of 88 nursing schools and 74 of 118 medical schools did not include any of the patient safety topics studied. The most frequent in both nursing and medicine was "interprofessional communication", followed by "quality of care" and basic aspects on "patient safety". The second victim phenomenon was present in only one curriculum of the total sample. Our study showed that patient safety, especially the second victim phenomenon, is still neglected in medical and nursing curricula in European universities, although positive initiatives were also found. Given the frequency with which adverse events occur in health centres and the need to prepare students to deal with them adequately, additional efforts are needed to introduce patient safety elements into medical and nursing education.
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JUSTIFICATION: Providing care to patients with several conditions and simultaneously taking several medications at home is inexorably growing in developed countries. This trend increases the chances of home caregivers experiencing diverse errors related with medication or care. OBJECTIVE: To determine the effectiveness of four different educational solutions compared to the natural intervention (absence of intervention) to provide a safer care at home by caregivers. METHOD: Prospective, parallel, and mixed research study with two phases. Candidates: Home-based caregivers caring a person with multiple comorbid conditions or polymedication who falls into one of the three profiles of patients defined for the study (oncology, cardiovascular, or pluripathological patients). First phase: Experts first answered an online survey, and then joined together to discuss the design and plan the content of educational solutions directed to caregivers including the identification of medication and home care errors, their causes, consequences, and risk factors. Second phase: The true experiment was performed using an inter- and intrasubject single-factor experimental design (five groups: four experimental groups against the natural intervention (control), with pre- and post-intervention and follow-up measures) with a simple random assignment, to determine the most effective educational solution (n = 350 participants). The participants will be trained on the educational solutions through 360 V, VR, web-based information, or psychoeducation. A group of professionals called the "Gold Standard" will be used to set a performance threshold for the caring or medication activities. The study will be carried out in primary care centers, hospitals, and caregivers' associations in the Valencian Community, Andalusia, Madrid, and Murcia. EXPECTED RESULTS: We expect to identify critical elements of risk management at home for caregivers and to find the most effective and optimal educational solution to reduce errors at home, increasing caregivers' motivation and self-efficacy whilst the impact of gender bias in this activity is reduced. TRIAL REGISTRATION: Clinical Trial NCT05885334.
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BACKGROUND: Oleocanthal and oleacein are olive oil phenolic compounds with well known anti-inflammatory and anti-oxidant properties. The main evidence, however, is provided by experimental studies. Few human studies have examined the health benefits of olive oils rich in these biophenols. Our aim was to assess the health properties of rich oleocanthal and oleacein extra virgin olive oil (EVOO), compared to those of common olive oil (OO), in people with prediabetes and obesity. METHODS: Randomised, double-blind, crossover trial done in people aged 40-65 years with obesity (BMI 30-40 kg/m2) and prediabetes (HbA1c 5.7-6.4%). The intervention consisted in substituting for 1 month the oil used for food, both raw and cooked, by EVOO or OO. No changes in diet or physical activity were recommended. The primary outcome was the inflammatory status. Secondary outcomes were the oxidative status, body weight, glucose handling and lipid profile. An ANCOVA model adjusted for age, sex and treatment administration sequence was used for the statistical analysis. RESULTS: A total of 91 patients were enrolled (33 men and 58 women) and finished the trial. A decrease in interferon-γ was observed after EVOO treatment, reaching inter-treatment differences (P = 0.041). Total antioxidant status increased and lipid and organic peroxides decreased after EVOO treatment, the changes reaching significance compared to OO treatment (P < 0.05). Decreases in weight, BMI and blood glucose (p < 0.05) were found after treatment with EVOO and not with OO. CONCLUSIONS: Treatment with EVOO rich in oleocanthal and oleacein differentially improved oxidative and inflammatory status in people with obesity and prediabetes.
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Antioxidantes , Estado Pré-Diabético , Masculino , Humanos , Feminino , Azeite de Oliva , Estudos Cross-Over , ObesidadeRESUMO
PURPOSE: To characterize the clinical changes occurring in the initial phase of the orthokeratology (OK) treatment for myopia correction, developing a model of prediction of the refractive changes in such phase. METHODS: Prospective study enrolling 64 eyes of 32 patients (range, 20-40 years) undergoing myopic OK treatment with the reverse geometry contact lens CRT (Paragon Vision Science). Changes in uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), refraction, corneal topography, ocular aberrations, and corneal epithelial thickness were evaluated during the first hour of OK lens wear and after 1 week of OK treatment. Multiple linear regression analysis was used to obtain a model to predict the short-term refractive effect of OK. RESULTS: The UCVA improved at each visit, reaching normal visual acuity values after a week (P<0.001) of OK treatment, which was consistent with the significant spherical equivalent (SE) reduction and central flattening (P<0.001). Multiple linear regression analysis revealed that one night change in refraction (ΔR×1N) could be predicted according to the following expression (P<0.001, R2=0.686): ΔR×1N=1.042+0.028×Age+1.014×BCET (baseline central epithelium thickness)-0.752×BKm (baseline mean keratometry)-1.405×BSE (baseline SE)+1.032×ΔR×1 h (change in SE after 1 hr of OK lens use). Similarly, a statistically relevant linear relationship was obtained for predicting the refractive change after 1 week (ΔR×1W) of OK use (P<0.001, R2=0.928): ΔR×1W=3.470-1.046×BSE-1.552×BBCVA (baseline BCVA)-0.391×BKm+0.450×ΔR×1 h. CONCLUSIONS: The immediate and short-term refractive effects of myopic OK with the reverse geometry contact lens CRT can be predicted with enough accuracy from baseline and first trial visits data.
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Miopia , Procedimentos Ortoceratológicos , Humanos , Córnea , Topografia da Córnea , Miopia/terapia , Estudos Prospectivos , Refração Ocular , Acuidade Visual , Adulto Jovem , AdultoRESUMO
The aim of this work was to recover phenolic compounds such as oleacein and oleocanthal from low commercial value olive oils destined for refining [lampante olive oil (LOO)]. For this, the ability of three extraction systems of phenols from oils was evaluated. A new quick and simple extraction method (NM) for obtaining phenols was developed, consisting of the acidified mixture MeOH/H2O (50:50) (v/v) 0.1% formic acid, and it was compared to a conventional method (CM) widely used for the analytical determination of phenolic compounds in olive oil using MeOH: H2O (80:20) (v/v). NM showed a higher yield for the extraction of oleacein with an increase of 14% compared to CM; no significant differences were observed in the extraction of oleocanthal between the two methods. The third method, using two formulations of deep eutectic solvents (DESs) based on ChCl, showed higher extractive efficiency for the two secoiridoids than CM and NM when DES consisted of ChCl and xylitol. On the other hand, the concentrations of oleacein and oleocanthal were determined in 14 samples of blended oils that were previously classified as extra virgin olive oil and LOO according to EU regulation. LOO contained amounts up to 109.89 and 140.16 mg/kg of oleacein and oleocanthal, respectively. Oleacein (>98%) and oleocanthal (>95%) were successfully recovered from phenolic extracts obtained from LOO oils through chromatographic separation and purification by semipreparative high-performance liquid chromatography. Therefore, these low-quality oils are an inexpensive source of bioactive substances.
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Aldeídos , Fenóis , Monoterpenos Ciclopentânicos , Solventes Eutéticos Profundos , Azeite de Oliva/análise , Fenóis/análiseRESUMO
Purpose: To review the scientific literature on the comparison of the efficacy of different corneal collagen crosslinking (CXL) protocols for the treatment of progressive keratoconus.Methods: Systematic review of randomized clinical trials (RCTs) on CXL outcomes. A search was carried out using the Cochrane Library, PubMed, EMBASE, Web of Science, Ovid MEDLINE, and Scopus databases. Internal validity was analyzed by applying the filter CASPe (Critical Appraisal Skills Program Spain).Results: The search yielded 1151 articles, and among these, 14 articles met the inclusion and exclusion criteria defined. Conventional (S) crosslinking (CXL) provided better topographic outcomes than transepithelial (TE) CXL, and S-CXL had a better therapeutic effect of corneal flattening than accelerated (A) CXL. The corneal thinning after CXL was lower with hypotonic riboflavin than with riboflavin-dextran. While one study demonstrated a better therapeutic effect of corneal flattening with S-CXL than with A-CXL, another study showed similar results between both techniques. No correlation was found between the depth of the demarcation line and topographic changes, which was not a direct measure of treatment effectiveness. Quality analysis of the literature reviewed yielded a mean score of 8.64, indicating that the RCTs evaluated had an overall acceptable quality.Conclusions: Good-quality RCTs comparing CXL techniques have been conducted, and most of them suggest that epi-off CXL can be considered the standard treatment for progressive keratoconus. TE-CXL and iontophoresis-assisted CXL are mainly indicated in patients with a risk of corneal scarring and patients with pain intolerance, respectively.
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Ceratocone , Fotoquimioterapia , Colágeno/uso terapêutico , Reagentes de Ligações Cruzadas/uso terapêutico , Humanos , Ceratocone/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêuticoRESUMO
Aging and fertility are two interconnected processes. From invertebrates to mammals, absence of the germline increases longevity. Here we show that loss of function of sul-2, the Caenorhabditis elegans steroid sulfatase (STS), raises the pool of sulfated steroid hormones, increases longevity and ameliorates protein aggregation diseases. This increased longevity requires factors involved in germline-mediated longevity (daf-16, daf-12, kri-1, tcer-1 and daf-36 genes) although sul-2 mutations do not affect fertility. Interestingly, sul-2 is only expressed in sensory neurons, suggesting a regulation of sulfated hormones state by environmental cues. Treatment with the specific STS inhibitor STX64, as well as with testosterone-derived sulfated hormones reproduces the longevity phenotype of sul-2 mutants. Remarkably, those treatments ameliorate protein aggregation diseases in C. elegans, and STX64 also Alzheimer's disease in a mammalian model. These results open the possibility of reallocating steroid sulfatase inhibitors or derivates for the treatment of aging and aging related diseases.
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Doença de Alzheimer/enzimologia , Doença de Alzheimer/patologia , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/enzimologia , Caenorhabditis elegans/fisiologia , Longevidade , Esteril-Sulfatase/metabolismo , Sulfatases/metabolismo , Animais , Modelos Animais de Doenças , Epistasia Genética , Gônadas/metabolismo , Camundongos , Fenótipo , Células Receptoras Sensoriais/metabolismo , Esteroides/metabolismoRESUMO
PURPOSE: To analyze and characterize the pattern of visual working distance (WD) and mobile phone usage distance (MPD) in a large population, analyzing the differences in these parameters according to the job profile. METHODS: Cross-sectional study consisting of a screening campaign evaluating the visual status of professionals from seven different environments. A total of 454 participants with a mean age of 41.5 years (range, 22-64 years) were revised. The screening campaign consisted of several rapid tests performed in a single session in the usual work environment of each participant, including measurement of WD, arm length, and MPD (VisionApp, VisionApp Solutions S.L.). RESULTS: WD was significantly longer than MPD (82.5 ± 150.6 vs. 31.9 ± 6.3 cm, p < .001), whereas no significant differences were found between arm length (74.3 ± 4.8 cm) and WD (p = .493). WD was below 80 cm in 89.6% (407/454) of participants, whereas MPD was below 40 cm in 89.0% (404/454). No significant correlation was found between WD and MPD (r = 0.126, p = .117). Statistically significant differences were detected among job profile subgroups in WD (p < .001), with military personnel showing significantly longer WD than other professionals (p ≤ 0.018). Significant differences were also found between job profile subgroups in MPD (p = .006), with shorter MPDs for shoe factory professionals compared to sellers (p = .046). CONCLUSIONS: WD and MPD vary significantly among individuals, but always showing a shorter MPD. WD varies significantly also according to the job profile, being necessary to consider this information when selecting the most optimal optical aid in each case, especially for the compensation of presbyopia.
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Telefone Celular/estatística & dados numéricos , Implante de Lente Intraocular , Ocupações , Facoemulsificação , Presbiopia/cirurgia , Pseudofacia/fisiopatologia , Visão Ocular/fisiologia , Adulto , Estudos Transversais , Feminino , Humanos , Lentes Intraoculares , Masculino , Pessoa de Meia-Idade , Lentes Intraoculares Multifocais , Presbiopia/fisiopatologia , Trabalho , Adulto JovemRESUMO
PURPOSE: To summarize the peer-reviewed literature on corneal structural changes after orthokeratology (OK) and to analyze the quality of the studies published. METHODS: An exhaustive search was carried out in the databases Pubmed MEDLINE, Web of Science and Scopus. Original studies in English, with a cohort or experimental design and analyzing the cellular and structural changes of the cornea after OK fitting for myopia correction were selected. The NewCastle-Ottawa Assessment Scale (NOS) tool was used to analyze the quality of the studies selected. RESULTS: The search provided a total of 1837 articles, of which 12 were selected following the inclusion and exclusion criteria. All studies had good quality according to the NOS tool (mean 7.58 ± 1.31). The mean ± standard deviation follow-up period of lens wear in the studies evaluated was 19.27 ± 33.97 months. The following reversible changes after OK have been reported: reduction in central epithelial basal cells, an increase in height and especially in width of superficial epithelial cells, as well as an increase in central stromal thickness and in the number of active keratocytes. Concerning corneal endothelium, only changes in terms of polymegathism were reported that were compatible with those observed for other types of contact lens wear. In relation to corneal sensitivity, there was a reduction during the use of OK, as well as in the nervous density of the sub-basal plexus at the central level, with some contradictory outcomes concerning the reversibility of these changes. CONCLUSION: OK produces reversible structural changes in the central epithelium and central anterior corneal stroma, as well as a decrease in the nerve density of the sub-basal plexus and corneal sensitivity. The quality of published studies evaluating these aspects is good, although more studies are needed to evaluate longer follow-up changes.
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Lentes de Contato , Miopia , Procedimentos Ortoceratológicos , Córnea , Topografia da Córnea , Humanos , Miopia/terapiaRESUMO
Intraocular lens (IOL) opacification is an infrequent complication of cataract surgery. Surface analysis has demonstrated that the opacification of IOLs is related to calcium or phosphate precipitation on or within the lenses, but the associated mechanisms are unknown, and the scientific literature is heterogeneous and limited to case series and retrospective studies. The purpose of this systematic review was to analyse the most frequent conditions associated with opacification of IOLs reported by studies. A search was carried out using the PubMed MEDLINE, Web of Science and Scopus databases. The quality of the studies selected was evaluated using the Pierson tool. The search provided a total of 811 articles, of which 39 were selected following the inclusion and exclusion criteria. The most common opacified lenses were hydrophilic IOLs according to our analysis. The mean time of appearance of lens opacification was 14.93 ± 17.82 months. The most frequent conditions associated with opacification of the IOLs were Descemet Stripping with Automated Endothelial Keratoplasty (DSAEK/DSEK) and diabetes mellitus (DM), followed by pars plana vitrectomy (PPV), blood hypertension (HT), and glaucoma. Concerning the quality analysis, the mean score was 7.00 ± 1.43 (scoring range from 0 to 10), indicating an acceptable quality of the case reports and retrospective studies. In conclusion, DSAEK/DSEK, DM, PPV, glaucoma and hypertension are conditions with potential risk of IOL opacification after cataract surgery, especially when implanting hydrophilic acrylic IOLs.
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Lentes Intraoculares/efeitos adversos , Complicações Pós-Operatórias , Falha de Prótese/etiologia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/efeitos adversos , Remoção de Dispositivo , Complicações do Diabetes , Glaucoma/complicações , Humanos , Hipertensão/complicações , Fatores de Risco , Fatores de Tempo , Vitrectomia/efeitos adversosRESUMO
PURPOSE: To evaluate the preliminary clinical outcomes of a new contact lens design for orthokeratology in hyperopia. METHODS: Prospective pilot study including 8 hyperopic eyes of 4 nonpresbyopic patients (24-44 years) undergoing orthokeratology with the Alexa H contact lens (Tiedra Pharmaceutical, Madrid, Spain), which is an aspheric pentacurve design. Visual, refractive, corneal topographic, and aberrometric changes were evaluated during a 1-month follow-up. Likewise, the presence of ocular surface alterations was evaluated by slit-lamp biomicroscopy during this follow-up. RESULTS: Mean noncyclopegic sphere decreased significantly from a mean prefitting value of 2.94±0.95 D to mean values of 1.18±1.19 (P=0.01) and 0.25±0.85 D (P=0.04) at 1 week and 1 month of lens wear, respectively. Statistically significant changes were detected at 1 week of use of the lenses in keratometry (P=0.03), asphericity (Q) (P=0.01), and the Zernike term for corneal spherical aberration (SA) (P=0.01). However, no significant changes were observed in uncorrected (P=0.68) and best-corrected distance visual acuity (P=0.18). Superficial corneal staining was observed after the first night of use in only 1 patient who was resolved spontaneously. Likewise, the induction of a "toroid-like" topographic pattern leading to poor visual outcome and suboptimal correction was observed in four eyes at the beginning of the treatment. This condition was solved in all cases by reducing the lens diameter. CONCLUSION: The Alexa H lens seems to be useful for providing an orthokeratologic correction of hyperopia, with generation of increased negative Q and SA, and central steepening. However, fitting guides must be improved to avoid suboptimal outcomes as those related to the "toroid-like" topographic pattern defined.
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Lentes de Contato , Hiperopia/terapia , Procedimentos Ortoceratológicos , Adulto , Topografia da Córnea , Feminino , Humanos , Hiperopia/fisiopatologia , Masculino , Projetos Piloto , Estudos Prospectivos , Desenho de Prótese , Ajuste de Prótese , Refração Ocular/fisiologia , Microscopia com Lâmpada de Fenda , Acuidade Visual/fisiologia , Adulto JovemRESUMO
Coenzyme Q (CoQ), a redox-active lipid, is comprised of a quinone group and a polyisoprenoid tail. It is an electron carrier in the mitochondrial respiratory chain, a cofactor of other mitochondrial dehydrogenases, and an essential antioxidant. CoQ requires a large set of enzymes for its biosynthesis; mutations in genes encoding these proteins cause primary CoQ deficiency, a clinically and genetically heterogeneous group of diseases. Patients with CoQ deficiency often respond to oral CoQ10 supplementation. Treatment is however problematic because of the low bioavailability of CoQ10 and the poor tissue delivery. In recent years, bypass therapy using analogues of the precursor of the aromatic ring of CoQ has been proposed as a promising alternative. We have previously shown using a yeast model that vanillic acid (VA) can bypass mutations of COQ6, a monooxygenase required for the hydroxylation of the C5 carbon of the ring. In this work, we have generated a human cell line lacking functional COQ6 using CRISPR/Cas9 technology. We show that these cells cannot synthesize CoQ and display severe ATP deficiency. Treatment with VA can recover CoQ biosynthesis and ATP production. Moreover, these cells display increased ROS production, which is only partially corrected by exogenous CoQ, while VA restores ROS to normal levels. Furthermore, we show that these cells accumulate 3-decaprenyl-1,4-benzoquinone, suggesting that in mammals, the decarboxylation and C1 hydroxylation reactions occur before or independently of the C5 hydroxylation. Finally, we show that COQ6 isoform c (transcript NM_182480) does not encode an active enzyme. VA can be produced in the liver by the oxidation of vanillin, a nontoxic compound commonly used as a food additive, and crosses the blood-brain barrier. These characteristics make it a promising compound for the treatment of patients with CoQ deficiency due to COQ6 mutations.
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Trifosfato de Adenosina/metabolismo , Ubiquinona/análogos & derivados , Ácido Vanílico/farmacologia , Sequência de Aminoácidos , Animais , Sistemas CRISPR-Cas/genética , Células HEK293 , Humanos , Mitocôndrias/metabolismo , Mutagênese Sítio-Dirigida , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Estrutura Terciária de Proteína , Espécies Reativas de Oxigênio/metabolismo , Alinhamento de Sequência , Ubiquinona/biossíntese , Ubiquinona/genética , Ubiquinona/metabolismoRESUMO
Factors such as lactation stage and premature and small-for-gestational conditions could lead to great inter-individual variability in the carotenoid content of human milk. The aim was to analyze the carotenoid content in colostrum and mature milk of preterm (PT) and full-term (FT) mothers to establish whether they are significantly different and, if so, the stage of lactation when the differences are established. Samples of blood, colostrum, and mature milk were collected from Spanish donating mothers who gave birth to PT or FT infants. Carotenoids from serum and milk samples were analyzed by HPLC-atmospheric pressure chemical ionization (APCI)-MS. Quantitatively, colostrum from PT mothers presented lower total carotenoid content when compared to that from FT mothers. The only exception was lutein, where levels were not different. The transition from colostrum to mature milk makes observed differences in the carotenoid content disappear, since there were no variances between PT and FT groups for both individual and total carotenoid content. The premature birth condition affects the quantitative carotenoid composition of the colostrum but has no effect on the lutein content. This fact could be related to the significant role of this xanthophyll in the development of infant retina and feasibly to cognitive function.
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Carotenoides/análise , Colostro/química , Recém-Nascido Prematuro , Lactação , Leite Humano/química , Nascimento a Termo , Estudos de Avaliação como Assunto , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Luteína/análise , Xantofilas/análiseRESUMO
Acyl-acyl carrier protein (ACP) desaturases (EC 1.14.19.2) are soluble enzymes that catalyse the insertion of a double bond into saturated fatty acid bound in saturated acyl chains bound to ACP in higher plants, producing cis-monounsaturated fatty acids. Three types of soluble acyl-ACP desaturases have been described: Δ(9)-acyl-ACP, Δ(6)-acyl-ACP and Δ(4)-acyl-ACP desaturases, which differ in the substrate specificity and the position in which the double bond is introduced. In the present work, Camelina sativa (CsSAD), Macadamia tetraphylla (MtSAD) and Dolichandra unguis-cati (DuSAD) desaturases were cloned, sequenced and characterized. Single copies of CsSAD, MtSAD and DuSAD with three, one and two different alleles, respectively, were found. The corresponding mature proteins were heterologously expressed in Escherichia coli for biochemical characterization in protein extracts. The recombinant CsSAD enzyme showed 300-fold higher specificity towards 18:0-ACP than 16:0-ACP. Similar profile exhibited MtSAD although the differences in the specificity were lower, around 170-fold higher for 18:0-ACP than 16:0-ACP. Furthermore, DuSAD presented a profile showing preference towards 16:0-ACP against 18:0-ACP, around twice more, being so a Δ(9) palmitoyl-ACP desaturase. Also, we reported the expression profile of CsSAD, which showed the highest levels of expression in expanding tissues that typically are very active in lipid biosynthesis such as developing seed endosperm. Moreover, the possibility to express a new desaturase in C. sativa (oilseed crop that store high levels of oil and is easy to transform) to create a new line rich in short monounsaturated fatty acid is discussed.
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Bignoniaceae/genética , Brassicaceae/genética , Macadamia/genética , Oxigenases de Função Mista/genética , Proteínas de Plantas/genética , Sequência de Aminoácidos , Bignoniaceae/metabolismo , Brassicaceae/metabolismo , Clonagem Molecular , Escherichia coli/genética , Macadamia/metabolismo , Oxigenases de Função Mista/metabolismo , Dados de Sequência Molecular , Organismos Geneticamente Modificados , Filogenia , Proteínas de Plantas/metabolismo , Alinhamento de SequênciaRESUMO
The last step in triacylglycerols (TAG) biosynthesis in oil seeds, the acylation of diacylglycerols (DAG), is catalysed by two types of enzymes: the acyl-CoA:diacylglycerol acyltransferase (DGAT) and phospholipid:diacylglycerol acyltransferase (PDAT). The relative contribution of these enzymes in the synthesis of TAG has not yet been defined in any plant tissue. In the presented work, microsomal preparations were obtained from sunflower and safflower seeds at different stages of development and used in DGAT and PDAT enzyme assays. The ratio between PDAT and DGAT activity differed dramatically between the two different species. DGAT activities were measured with two different acyl acceptors and assay methods using two different acyl-CoAs, and in all cases the ratio of PDAT to DGAT activity was significantly higher in safflower than sunflower. The sunflower DGAT, measured by both methods, showed significant higher activity with 18:2-CoA than with 18:1-CoA, whereas the opposite specificity was seen with the safflower enzyme. The specificities of PDAT on the other hand, were similar in both species with 18:2-phosphatidylcholine being a better acyl donor than 18:1-PC and with acyl groups at the sn-2 position utilised about fourfold the rate of the sn-1 position. No DAG:DAG transacylase activity could be detected in the microsomal preparations.
Assuntos
Aciltransferases/metabolismo , Carthamus tinctorius/enzimologia , Diacilglicerol O-Aciltransferase/metabolismo , Helianthus/enzimologia , Microssomos/enzimologia , Sementes/enzimologia , Carthamus tinctorius/crescimento & desenvolvimento , Ácidos Graxos/metabolismo , Helianthus/crescimento & desenvolvimento , Metabolismo dos Lipídeos , Modelos Biológicos , Sementes/crescimento & desenvolvimento , Especificidade por Substrato , Triglicerídeos/metabolismoRESUMO
Resumen
Introducción: la hemodiálisis (HD) es un procedimiento terapéutico sustitutivo para pacientes con Enfermedad Renal (ER). Actualmente, se observa en nuestro medio que la hemodiálisis ha tenido una evolución lenta además de ser un procedimiento invasivo que no está exento de complicaciones.
Objetivo: identificar las principales complicaciones que deterioran la calidad de vida de pacientes que acudieron a una Unidad de Hemodiálisis de San Luis Potosí, entre octubre y noviembre de 2010.
Metodología: diseño de estudio descriptivo y transversal, realizado en una Unidad de Hemodiálisis de San Luis Potosí, se incluyeron pacientes que acudieron a sesiones de hemodiálisis regularmente por prescripción médica, se excluyeron pacientes que no cumplieron con este requisito y se eliminaron a quienes dejaron de acudir a la terapia sustitutiva. Se diseñó, validó y aplicó un instrumento con 26 ítems; cuya prueba piloto obtuvo un alfa de Cronbach de 0.68. El análisis de datos se realizó con el paquete estadístico SPSS versión 17.0.
Resultados: se encuestaron 52 pacientes, 57.7% mujeres y 42.3% varones; la diabetes mellitus e hipertensión arterial fueron los principales factores etiológicos (44.2%). 69.2% cuenta con catéter como acceso vascular. Las principales complicaciones fueron: calambres71.2%, hipertensión 67.3%, cefalea 55.8%, hipotensión 55.8%, vómito 48.1% y disnea 34.6%. 43.3% refirió la infección como causa de cambio de catéter.
Conclusiones: los pacientes hemodializados siempre presentaron complicaciones durante el proceso, mismas que evidencian un deterioro en su calidad de vida.
Abstract
Introduction: Hemodialysis is a substitutive therapeutic alternative procedure for patients with renal disease. Currently ¡t can be noticed that hemodialysis, has had a slow evolution and it is an invasive procedure which is not exempt from complications. Objective: To identify the main complications that impair quality of life in patients who come to an Hemodialysis unit in San Luis Potosí, México; during the months of October - November 2010. Methodology: Descriptive and cross-sectional study which took place in an Hemodialysis Unit of San Luis Potosí.; it included patients who attend to regular sessions of hemodialysis according to their prescriptions, patients who did not meet this requirement were excluded and those who stopped coming to replacement therapy were eliminated. A questionnaire consisting of 26 items was designed, validated and implemented; its pilot test obtained a Cronbach alpha of 0.68. The data analysis was performed using SPSS version 17.0.
Results: 52 patients were surveyed, 57.7% female and 42.3% male. Diabetes mellitus and hypertension were the main etiological factors with 44.2%.; 69.2% have a catheter as a vascular access. The main complications were: cramps 71.2%, hypertension 67.3%, headache 55.8%, hypotension 55.8% vomiting 48.1 %, dyspnea 34.6% and 43.3% referred infection as the cause of change of catheter.
Conclusions: Hemodialysis patients always had complications during the process. These complications were evidence of deterioration in their quality of life.