Objectives
The aim of this study is to evaluate the prevalence, associated factors, and time for diabetic retinopathy (DR) development in Ecuadorian patients with type 2 diabetes (DM2) followed for ...10 years.
Methods
A retrospective cohort study between 2007 and 2017 included 487 patients with DM2 who had at least one dilated fundus eye examination in Diabetes Center in a primary-health-care level followed up for ten years. Data was collected from clinical records. Sociodemographic and laboratory variables were analysed, determining their association (mean difference and bivariate logistic regression) with DR. Survival time was calculated through life tables and Kaplan-Meier analysis.
Results
The prevalence of DR was 19.95% during the 10-year follow-up period. The median time for developing DR was 28.53 (95% CI: 26.89–27.05), showing that 50% of patients have the risk (HR: 4.57) to develop DR in the third decade of DM disease diagnosis. The significant risk factors for progression of DR were duration of DM2, high glycosylated hemoglobin level > 7% (HbA1c Expβ: 1.709, 95% CI: 1.00–2.89), systemic hypertension (HNT Expβ: 2.348 Expβ: 2.348 95% CI: 1.17–4.70%) 95% CI: 1.17–4.70%), low glomerular filtration rate (Expβ: 1.805, GFR, < 60 ml/min/sc1.73) (95% CI: 1.10–2.94) and albuminuria (Expβ: 2.48 Expβ: 2.48 95% CI: 1.49–4.13).
Conclusions
Half of the patients with DM2 treated in a primary level of care will develop DR in the third decade of the disease. There are risk factors related to development of DR, such as low GFR, high HbA1c, albuminuria and HTN. Low GFR, high HbA1c, albuminuria and high blood pressure are related with the presence of retinopathy in diabetes patients.
In most tissues, cell division is coordinated with increases in mass (i.e., growth). To understand this coordination, we altered rates of division in cell clones or compartments of the
Drosophila ...wing and measured the effects on growth. Constitutive overproduction of the transcriptional regulator dE2F increased expression of the S- and M-phase initiators Cyclin E and String (Cdc25), thereby accelerating cell proliferation. Loss of dE2F or overproduction of its corepressor, RBF, retarded cell proliferation. These manipulations altered cell numbers over a 4- to 5-fold range but had little effect on clone or compartment sizes. Instead, changes in cell division rates were offset by changes in cell size. We infer that dE2F and RBF function specifically in cell cycle control, and that cell cycle acceleration is insufficient to stimulate growth. Variations in dE2F activity could be used to coordinate cell division with growth.
Watersheds are defined as a set of lands where water drainage occurs through rivers and their tributaries. A large quantity of water resources exist in the state of Maranhão, Brazil, where rivers and ...their basins must meet environmental quality standards defined by the limits set out in national environmental council (CONAMA) legislation 357/05 for physicochemical and microbiological parameters, including parasites. Multivariate statistical techniques were applied to study the temporal and spatial variations in water quality of a segment of the Pindaré River. The data set included nine parameters for three sampling points over eleven months. Principal component analysis grouped the monitored sampling points into four clusters and identified electrical conductivity, temperature, total dissolved solids (TDS), pH, salinity, and Escherichia coli as being associated with the dry season and nitrite, nitrate, and turbidity as being associated with the rainy season. Three principal components explained 83.80% of the data variance during the rainy and dry seasons. The evaluated correlations indicated that during the rainy season, nitrite (~0.18 mg L−1) and turbidity (~46.00 NTU) levels were the highest, but pH was at its lowest (~6.61). During the dry season, TDS (~155.00 mg L−1) and pH (~8.10) were highest, and E. coli bacteria was more abundant.
Mammalian cyclin D–Cdk4 complexes have been characterized as growth factor‐responsive cell cycle regulators. Their levels rise upon growth factor stimulation, and they can phosphorylate and thus ...neutralize Retinoblastoma (Rb) family proteins to promote an E2F‐dependent transcriptional program and S‐phase entry. Here we characterize the in vivo function of Drosophila Cyclin D (CycD). We find that Drosophila CycD–Cdk4 does not act as a direct G1/S‐phase regulator, but instead promotes cellular growth (accumulation of mass). The cellular response to CycD–Cdk4‐driven growth varied according to cell type. In undifferentiated proliferating wing imaginal cells, CycD–Cdk4 caused accelerated cell division (hyperplasia) without affecting cell cycle phasing or cell size. In endoreplicating salivary gland cells, CycD–Cdk4 caused excessive DNA replication and cell enlargement (hypertrophy). In differentiating eyes, CycD–Cdk4 caused cell enlargement (hypertrophy) in post‐mitotic cells. Interaction tests with a Drosophila Rb homolog, RBF, indicate that CycD–Cdk4 can counteract the cell cycle suppressive effects of RBF, but that its growth promoting activity is mediated at least in part via other targets.
Summary
Dual‐specificity protein phosphatases (DSPs) are important regulators of a wide variety of protein kinase signaling cascades in animals, fungi and plants. We previously identified a cluster ...of putative DSPs in Arabidopsis (including At3g52180 and At3g01510) in which the phosphatase domain is related to that of laforin, the human protein mutated in Lafora epilepsy. In animal and fungal systems, the laforin DSP and the beta‐regulatory subunits of AMP‐regulated protein kinase (AMPK) and Snf‐1 have all been demonstrated to bind to glycogen by a glycogen‐binding domain (GBD). We present a bioinformatic analysis which shows that these DSPs from Arabidopsis, together with other related plant DSPs, share with the above animal and fungal proteins a widespread and ancient carbohydrate‐binding domain. We demonstrate that DSP At3g52180 binds to purified starch through its predicted carbohydrate‐binding region, and that mutation of key conserved residues reduces this binding. Consistent with its ability to bind exogenous starch, DSP At3g52180 was found associated with starch purified from Arabidopsis plants and suspension cells. Immunolocalization experiments revealed a co‐localization with chlorophyll, placing DSP At3g52180 in the chloroplast. Gene‐expression data from different stages of the light–dark cycle and across a wide variety of tissues show a strong correlation between the pattern displayed by transcripts of the At3g52180 locus and that of genes encoding key starch degradative enzymes. Taken together, these data suggest the hypothesis that plant DSPs could be part of a protein assemblage at the starch granule, where they would be ideally situated to regulate starch metabolism through reversible phosphorylation events.
Purpose
We describe our series of 4 patients with megalencephaly-capillary malformation syndrome (MCAP) and review the literature in order to assess the optimal treatment for the associated ...hydrocephalus.
Methods
We review our institutional series of hydrocephalus associated with MCAP and review the literature, analyzing the causes that could originate the hydrocephalus and the different types of treatments proposed for them.
Results
Of our patients treated with ventriculoperitoneal (VP) shunt, one suffered a surgical revision of the shunt and died due to a cranial trauma unrelated to her syndrome or the previous shunt surgery, and the other did not undergo surgical revisions until the end of her follow-up. Our patients treated with endoscopic third ventriculostomy (ETV) have improved their symptomatology and have not suffered of any complications related to the hydrocephalus after the ETV surgery.
Conclusions
We update the treatment of MCAP-associated hydrocephalus and propose ETV as a valid treatment, as it seems a safe procedure with a low rate of complications.
•TBM Penetration Rate prediction with Long-Short Term Memory Neural Network.•Accuracy estimation using only machine parameters, without geological parameters.•Prediction up to 5 rings forward in the ...future (9 m ahead).•Use of SHAP: explainable AI tool to understand the most impactful features.•Cross-tunnel prediction: training on Exploratory tunnel and testing on Main.
Penetration rate prediction of Tunnel Boring Machines (TBM) is critical for understanding excavation performances. In this paper, we investigate the possibility of developing machine learning models that accurately predict the Penetration Rate of a TBM using only machine parameters. We leveraged two datasets collected from the Exploratory and Main excavation of the Lot Mules 2–3 of the Brenner Base Tunnel Project. We compared the performance of two different Artificial Neural Network architectures, one based on feedforward architecture and the other on long short-term memory (LSTM). We also studied which features lead to a good estimation of the penetration rate using SHAP, an explainable AI tool, discovering that the Specific Energy (SE) and the Cutterhead Power (CP) are the most impactful features. We also explore the possibility of performing cross-tunnel prediction by training the model on the Exploratory tunnel and testing it on the Main Tunnel, obtaining promising results.
The three mammalian D-type cyclins are thought to promote progression through the G1 phase of the cell cycle as regulatory subunits of cyclin-dependent kinase 4 and 6. In addition, they have been ...proposed to control the activity of various transcription factors without a partner kinase. Here we describe phenotypic consequences of null mutations in Cyclin D, the single D-type cyclin gene in Drosophila. As previously observed with null mutations in the single Drosophila Cdk4 gene, these mutations do not primarily affect progression through the G1 phase. Moreover, the apparently indistinguishable phenotypes of double (CycD and Cdk4) and single mutants (CycD or Cdk4) argue against major independent functions of Cyclin D and Cdk4. The reduced cellular and organismal growth rates observed in both mutants indicate that Cyclin D-Cdk4 acts as a growth driver.
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