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We study the statistical interdependence between daily precipitation and daily extreme temperature for regions of Mexico (14 climatic stations, period 1960-2020) and Colombia (7 climatic stations, period 1973-2020) using linear (cross-correlation and coherence) and nonlinear (global phase synchronization index, mutual information, and cross-sample entropy) synchronization metrics. The information shared between these variables is relevant and exhibits changes when comparing regions with different climatic conditions. We show that precipitation and temperature records from La Mojana are characterized by high persistence, while data from Mexico City exhibit lower persistence (less memory). We find that the information exchange and the level of coupling between the precipitation and temperature are higher for the case of the La Mojana region (Colombia) compared to Mexico City (Mexico), revealing that regions where seasonal changes are almost null and with low temperature gradients (less local variability) tend to display higher synchrony compared to regions where seasonal changes are very pronounced. The interdependence characterization between precipitation and temperature represents a robust option to characterize and analyze the collective dynamics of the system, applicable in climate change studies, as well as in changes not easily identifiable in future scenarios.

Metronidazole (MTZ) is the most common drug used against Trichomonas vaginalis ( T. vaginalis ) infections; however, treatment failures and high rates of recurrence of trichomoniasis have been reported, suggesting the presence of resistance in T. vaginalis to MTZ. Therefore, research into new therapeutic options against T. vaginalis infections has become increasingly urgent. This study investigated the trichomonacidal activity of a series of five imidazole carbamate compounds (AGR-1, AGR-2, AGR-3, AGR-4, and AGR-5) through in vitro susceptibility assays to determine the IC 50 value of each compound. All five compounds demonstrated potent trichomonacidal activity, with IC 50 values in the nanomolar range and AGR-2 being the most potent (IC 50 400 nM). To gain insight into molecular events related to AGR-induced cell death in T. vaginalis , we analyzed the expression profiles of some metabolic genes in the trophozoites exposed to AGR compounds and MTZ. It was found that both AGR and MTZ compounds reduced the expression of the glycolytic genes ( CK , PFK , TPI , and ENOL ) and genes involved in metabolism ( G6PD , TKT , TALDO , NADHOX , ACT , and TUB ), suggesting that disturbing these key metabolic genes alters the survival of the T. vaginalis parasite and that they probably share a similar mechanism of action. Additionally, the compounds showed low cytotoxicity in the Caco-2 and HT29 cell lines, and the results of the ADMET analysis indicated that these compounds have pharmacokinetic properties similar to those of MTZ. The findings offer significant insights that can serve as a basis for future in vivo studies of the compounds as a potential new treatment against T. vaginalis .

This research presents an experimental study focused on measuring temperature at the tool flank during the up-milling process at high cutting speed. The proposed system deals with emissivity compensation through a two-photodetector system and during calibration. A ratio pyrometer composed of two photodetectors and a multimode fiber-optic coupler is employed to capture the radiation emitted by the cutting insert. The pyrometer is calibrated using an innovative calibration system that addresses theoretical discrepancies arising from various factors affecting the measurement of cutting temperature. This calibration system replicates the milling process to generate a calibration curve. Experimentally, AISI 4140 steel is machined with coated tungsten carbide inserts, using cutting speeds of 300 and 400 m/min, and feed rates of 0.08 and 0.16 mm/tooth. The results reveal a maximum recorded cutting temperature of 518 °C and a minimum of 304 °C. The cutting temperature tends to increase with higher cutting speeds and feed rates, with cutting speed being the more influential factor in this increase. Both the pyrometer calibration and experimental outcomes yield satisfactory results. Finally, the results showed that the process and the device prove to be a convenient, effective, and precise method of measuring cutting temperature in machine processes.

Metastasis remains the leading cause of mortality in prostate cancer patients. The presence of tumor cells in lymph nodes is an established prognostic indicator for several cancer types, such as melanoma, breast, oral, pancreatic, and cervical cancers. Emerging evidence highlights the role of microRNAs enclosed within extracellular vesicles as facilitators of molecular communication between tumors and metastatic sites in the lymph nodes. This study aims to investigate the potential diagnostic utility of EV-derived microRNAs in liquid biopsies for prostate cancer. By employing microarrays on paraffin-embedded samples, we characterized the microRNA expression profiles in metastatic lymph nodes, non-metastatic lymph nodes, and primary tumor tissues of prostate cancer. Differential expression of microRNAs was observed in metastatic lymph nodes compared to prostate tumors and non-metastatic lymph node tissues. Three microRNAs (miR-140-3p, miR-150-5p, and miR-23b-3p) were identified as differentially expressed between tissue and plasma samples. Furthermore, we evaluated the expression of these microRNAs in exosomes derived from prostate cancer cells and plasma samples. Intriguingly, high Gleason score samples exhibited the lowest expression of miR-150-5p compared to control samples. Pathway analysis suggested a potential regulatory role for miR-150-5p in the Wnt pathway and bone metastasis. Our findings suggest EV-derived miR-150-5p as a promising diagnostic marker for identifying patients with high-grade Gleason scores and detecting metastasis at an early stage.

Giardiasis, which is caused by Giardia lamblia infection, is a relevant cause of morbidity and mortality worldwide. Because no vaccines are currently available to treat giardiasis, chemotherapeutic drugs are the main options for controlling infection. Evidence has shown that the nitro drug nitazoxanide (NTZ) is a commonly prescribed treatment for giardiasis; however, the mechanisms underlying NTZ's antigiardial activity are not well-understood. Herein, we identified the glucose-6-phosphate::6-phosphogluconate dehydrogenase (GlG6PD::6PGL) fused enzyme as a nitazoxanide target, as NTZ behaves as a GlG6PD::6PGL catalytic inhibitor. Furthermore, fluorescence assays suggest alterations in the stability of GlG6PD::6PGL protein, whereas the results indicate a loss of catalytic activity due to conformational and folding changes. Molecular docking and dynamic simulation studies suggest a model of NTZ binding on the active site of the G6PD domain and near the structural NADP + binding site. The findings of this study provide a novel mechanistic basis and strategy for the antigiardial activity of the NTZ drug.

Bisphenol A (BPA) is a ubiquitous synthetic compound used as a monomer in the production of polycarbonate plastics and epoxy resins. Even at low doses, BPA has been associated with the molecular progression of diseases such as obesity, metabolic syndrome, and hormone-regulated cancers due to its activity as an endocrine-disrupting chemical (EDC). Consequently, the use of BPA has been regulated worldwide by different health agencies. BPA structural analogs such as bisphenol S and bisphenol F (BPS and BPF) have emerged as industrial alternatives, but their biological activity in the molecular progression of cancer remains unclear. Prostate cancer (PCa) is a hormone-dependent cancer, and the role of BPA structural analogs in PCa progression is still undescribed. In this work, we use an in vitro model to characterize the transcriptomic effect of low-concentration exposure to bisphenol A, S, or F in the two main stages of the disease: androgen dependency (LNCaP) and resistance (PC-3). Our findings demonstrated that the low concentration exposure to each bisphenol induced a differential effect over PCa cell lines, which marks the relevance of studying the effect of EDC compounds through all the stages of the disease.

Wire arc additive manufacturing (WAAM) is renowned for its high deposition rate, enabling the production of large parts. However, the process has challenges such as porosity formation, residual stresses, and cracking when manufacturing aluminum parts. This study focuses on ana-lyzing the porosity of AA5356 walls manufactured using the WAAM process with the Fronius cold metal transfer system (Wels, Austria). The walls were machined to obtain specimens for tensile testing. The study used computed tomography and the tensile test to analyze the specimens' porosity and its potential relation to tensile strength. The process parameters analyzed were travel speed, cooling time, and path strategy. In conclusion, increasing travel speed and cooling time significantly affects pore diameter due to the lower heat input to the weld zone. Porosity can be reduced when diminishing heat accumulation. The results indicate that an increase in travel speed produces a slight decrease in porosity. Specifically, the total pore volume diminishes from 0.42 to 0.36 mm 3 when increasing the travel speed from 700 to 950 mm/min. The ultimate tensile strength and maximum elongation of the 'back and forth' strategy are slightly higher than those of the 'go' strategy. After tensile testing, the ultimate tensile strength and yield strength did not show any relation to the porosity measured by computed tomography. The percentage of the pore total volume over the measured volume was lower than 0.12% for all the scanned specimens.

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Persistent high-risk human papillomavirus infection is the main risk factor for cervical cancer establishment, where the viral oncogenes E6 and E7 promote a cancerous phenotype. Metabolic reprogramming in cancer involves alterations in glutamine metabolism, also named glutaminolysis, to provide energy for supporting cancer processes including migration, proliferation, and production of reactive oxygen species, among others. The aim of this work was to analyze the effect of HPV16 E6 and E7 oncoproteins on the regulation of glutaminolysis and its contribution to cell proliferation. We found that the E6 and E7 oncoproteins exacerbate cell proliferation in a glutamine-dependent manner. Both oncoproteins increased the levels of transporter SNAT1, as well as GLS2 and GS enzymes; E6 also increased LAT1 transporter protein levels, while E7 increased ASCT2 and xCT. Some of these alterations are also regulated at a transcriptional level. Consistently, the amount of SNAT1 protein decreased in Ca Ski cells when E6 and E7 expression was knocked down. In addition, we demonstrated that cell proliferation was partially dependent on SNAT1 in the presence of glutamine. Interestingly, SNAT1 expression was higher in cervical cancer compared with normal cervical cells. The high expression of SNAT1 was associated with poor overall survival of cervical cancer patients. Our results indicate that HPV oncoproteins exacerbate glutaminolysis supporting the malignant phenotype.

Protozoan parasites, such as Giardia lamblia and Trichomonas vaginalis , cause the most prevalent infections in humans in developing countries and provoke significant morbidity and mortality in endemic countries. Despite its side-effects, metronidazole is still the drug of choice as a giardiacidal and trichomonacidal tissue-active agent. However, the emergence of metronidazole resistance and its evolved strategies of parasites to evade innate host defenses have hindered the identification and development of new therapeutic strategies against these parasites. Here, we tested five synthesized benzimidazole derivatives as possible drugs for treating giardiasis and trichomoniasis, probing the bifunctional enzyme glucose 6-phosphate dehydrogenase::6-phosphogluconolactone from G. lamblia (GlG6PD::6PGL) and T. vaginalis (TvG6PD::6PGL) as a drug target. The investigated benzimidazole derivatives were H-B2M1 , H-B2M2 , H 2 N-BZM6 , O 2 N-BZM7 , and O 2 N-BZM9 . The recombinant enzymes were used in inhibition assays, and in silico computational predictions and spectroscopic studies were applied to follow the structural alteration of the enzymes and identify the possible mechanism of inhibition. We identified two potent benzimidazole compounds ( O 2 N-BZM7 and O 2 N-BZM9 ), which are capable of inhibiting both protozoan G6PD::6PGL enzymes and in vitro assays with these parasites, showing that these compounds also affect their viability. These results demonstrate that other therapeutic targets of the compounds are the enzymes GlG6PD::6PGL and TvG6PD::6PGL, which contribute to their antiparasitic effect and their possible use in antigiardial and trichomonacidal therapies.

High-risk human papillomavirus (HPV) infection is the main risk factor for cervical cancer (CC) development, where the continuous expression of E6 and E7 oncoproteins maintain the malignant phenotype. In Mexico, around 70% of CC cases are diagnosed in advanced stages, impacting the survival of patients. The aim of this work was to identify biomarkers affected by HPV-16 E6 and E7 oncoproteins that impact the prognosis of CC patients. Expression profiles dependent on E6 and E7 oncoproteins, as well as their relationship with biological processes and cellular signaling pathways, were analyzed in CC cells. A comparison among expression profiles of E6- and E7-expressing cells and that from a CC cohort obtained from The Cancer Genome Atlas (TCGA) demonstrated that the expression of 13 genes impacts the overall survival (OS). A multivariate analysis revealed that the downregulated expression of RIPOR2 was strongly associated with a worse OS. RIPOR2, including its transcriptional variants, were overwhelmingly depleted in E6- and E7-expressing cells. Finally, in a Mexican cohort, it was found that in premalignant cervical lesions, RIPOR2 expression decreases as the lesions progress; meanwhile, decreased RIPOR2 expression was also associated with a worse OS in CC patients.

Despite of the capacity that several drugs have for specific inhibition of the androgen receptor (AR), in most cases, PCa progresses to an androgen-independent stage. In this context, the development of new targeted therapies for prostate cancer (PCa) has remained as a challenge. To overcome this issue, new tools, based on nucleic acids technology, have been developed. Aptamers are small oligonucleotides with a three-dimensional structure capable of interacting with practically any desired target, even large targets such as mammalian cells or viruses. Recently, aptamers have been studied for treatment and detection of many diseases including cancer. In PCa, numerous works have reported their use in the development of new approaches in diagnostics and treatment strategies. Aptamers have been joined with drugs or other specific molecules such as silencing RNAs (aptamer-siRNA chimeras) to specifically reduce the expression of oncogenes in PCa cells. Even though these studies have shown good results in the early stages, more research is still needed to demonstrate the clinical value of aptamers in PCa. The aim of this review was to compile the existing scientific literature regarding the use of aptamers in PCa in both diagnosis and treatment studies. Since Prostate-Specific Membrane Antigen (PSMA) aptamers are the most studied type of aptamers in this field, special emphasis was given to these aptamers.

Chronic Obstructive Pulmonary Disease (COPD) is a complex and heterogeneous disease, with pulmonary and extrapulmonary manifestations, which leads to the need to personalize the assessment and treatment of these patients. The latest updates of national and international guidelines for the management of COPD reveal the importance of respiratory rehabilitation (RR) and its role in improving symptoms, quality of life, and psychosocial sphere of patients. Within RR, the inspiratory muscle training (IMT) has received special interest, showing benefits in maximum inspiratory pressure, perception of well-being, and health status in patients with chronic heart disease, respiratory diseases, and dyspnea during exercise. The aim of this review is to assess the efficacy of IMT in COPD patients through the use of inspiratory muscle training devices, compared with respiratory rehabilitation programs without inspiratory muscle training. In the last years, many mechanical devices focused on inspiratory muscle training have been developed, some of them, such as the AirOFit PRO™, PowerBreath ® , or FeelBreathe ® , have shown clear benefits. The active search for candidate patients to undergo the RR program with inspiratory muscle training using this type of device in COPD patients represents an advance in the treatment of this disease, with direct benefits on the quality of life of the patients. In this article, we review the available evidence on IMT in these patients and describe the different devices used for it.

Trichomoniasis is a sexually transmitted disease with a high incidence worldwide, affecting 270 million people. Despite the existence of a catalog of available drugs to combat this infection, their extensive use promotes the appearance of resistant Trichomonas vaginalis ( T. vaginalis ), and some side effects in treated people, which are reasons why it is necessary to find new alternatives to combat this infection. In this study, we investigated the impact of an in-house library comprising 55 compounds on the activity of the fused T. vaginalis G6PD::6PGL (TvG6PD::6PGL) protein, a protein mediating the first reaction step of the pentose phosphate pathway (PPP), a crucial pathway involved in the parasite's energy production. We found four compounds: JMM-3, CNZ-3, CNZ-17, and MCC-7, which inhibited the TvG6PD::6PGL protein by more than 50%. Furthermore, we determined the IC 50 , the inactivation constants, and the type of inhibition. Our results showed that these inhibitors induced catalytic function loss of the TvG6PD::6PGL enzyme by altering its secondary and tertiary structures. Finally, molecular docking was performed for the best inhibitors, JMM-3 and MCC-7. All our findings demonstrate the potential role of these selected hit compounds as TvG6PD::6PGL enzyme selective inhibitors.

The computer numerical control (CNC) machine has recently taken a fundamental role in the manufacturing industry, which is essential for the economic development of many countries. Current high quality production standards, along with the requirement for maximum economic benefits, demand the use of tool condition monitoring (TCM) systems able to monitor and diagnose cutting tool wear. Current TCM methodologies mainly rely on vibration signals, cutting force signals, and acoustic emission (AE) signals, which have the common drawback of requiring the installation of sensors near the working area, a factor that limits their application in practical terms. Moreover, as machining processes require the optimal tuning of cutting parameters, novel methodologies must be able to perform the diagnosis under a variety of cutting parameters. This paper proposes a novel non-invasive method capable of automatically diagnosing cutting tool wear in CNC machines under the variation of cutting speed and feed rate cutting parameters. The proposal relies on the sensor information fusion of spindle-motor stray flux and current signals by means of statistical and non-statistical time-domain parameters, which are then reduced by means of a linear discriminant analysis (LDA); a feed-forward neural network is then used to automatically classify the level of wear on the cutting tool. The proposal is validated with a Fanuc Oi mate Computer Numeric Control (CNC) turning machine for three different cutting tool wear levels and different cutting speed and feed rate values.

The use of three-dimensional porous scaffolds derived from decellularized extracellular matrix (ECM) is increasing for functional repair and regeneration of injured bone tissue. Because these scaffolds retain their native structures and bioactive molecules, in addition to showing low immunogenicity and good biodegradability, they can promote tissue repair and regeneration. Nonetheless, imitating these features in synthetic materials represents a challenging task. Furthermore, due to the complexity of bone tissue, different processes are necessary to maintain these characteristics. We present a novel approach using decellularized ECM material derived from bovine cancellous bone by demineralization, decellularization, and hydrolysis of collagen to obtain a three-dimensional porous scaffold. This study demonstrates that the three-dimensional porous scaffold obtained from bovine bone retained its osteoconductive and osteoinductive properties and presented osteogenic potential when seeded with human Wharton's jelly mesenchymal stromal cells (hWJ-MSCs). Based on its characteristics, the scaffold described in this work potentially represents a therapeutic strategy for bone repair.

The role of leukotrienes (LTs) in the pathogenesis of systemic sclerosis (SSc) needs clarification. We analyzed the association of salivary (sa) and plasma (p) levels (pg/mL) of cysteinyl-leukotrienes (CysLT) and LTB4 with SSc vascular manifestations and nailfold capillaroscopy (NFC) in a cross-sectional study. Patients and healthy controls were evaluated for vascular manifestations and NFC. LTs were compared between groups as follows: SSc with or SSc without vascular features and controls, and by NFC parameters. Twenty SSc patients and 16 volunteers were recruited; Raynaud's phenomenon (RP) history (SSc: saCysLT 99.4 ± 21.8 vs. controls: 23.05 ± 23.7, p = 0.01), RP at examination (SSc: saCysLT 129.3 ± 24.6 vs. controls: 23.05 ± 22.46, p = 0.01; pCysLT SSc: 87.5 ± 11.2 vs. controls: 32.37 ± 10.75, p = 0.002), capillary loss (saCysLT 138.6 ± 26.7 vs. 23.05 ± 21.6, p = 0.0007; saLTB4 3380.9 ± 426.6 vs. 1216.33 ± 346.1, p = 0.0005), "late" scleroderma pattern vs. controls (saCysLT 205.6 ± 32 vs. 23 ± 19.6, p = 0.0002; saLTB4 4564.9 ± 503.6 vs. 1216.3 ± 308.3; p < 0.0001) were all significant. Late patterns had higher levels (saCysLT, p = 0.002; LTB4 p = 0.0006) compared to active and early patterns (LTB4, p = 0.0006), and giant capillaries ( p = 0.01) showed higher levels of LTs. Levels of pCysLT were higher in patients with RP at examination vs. patients without RP; saCysLT and LTB4 were higher in SSc group with vs. without capillary loss. LTs could be involved in the pathophysiology of vascular abnormalities. Further research is required to determine if blocking LTs could be a therapeutic target for SSc vascular manifestations.

Gliomas are heterogeneous, solid, and intracranial tumors that originate from glial cells. Malignant cells from the tumor undergo metabolic alterations to obtain the energy required for proliferation and the invasion of the cerebral parenchyma. The alterations in the expression of the genes related to the metabolic pathways can be detected in biopsies of gliomas of different CNS WHO grades. In this study, we evaluated the expression of 16 candidate reference genes in the HMC3 microglia cell line. Then, statistical algorithms such as BestKeeper, the comparative ΔC T method, geNorm, NormFinder, and RefFinder were applied to obtain the genes most suitable to be considered as references for measuring the levels of expression in glioma samples. The results show that PKM and TPI1 are two novel genes suitable for genic expression studies on gliomas. Finally, we analyzed the expression of genes involved in metabolic pathways in clinical samples of brain gliomas of different CNS WHO grades. RT-qPCR analysis showed that in CNS WHO grade 3 and 4 gliomas, the expression levels of HK1 , PFKM , GAPDH , G6PD , PGD1 , IDH1 , FASN , ACACA , and ELOVL2 were higher than those of CNS WHO grade 1 and 2 glioma biopsies. Hence, our results suggest that reference genes from metabolic pathways have different expression profiles depending on the stratification of gliomas and constitute a potential model for studying the development of this type of tumor and the search for molecular targets to treat gliomas.

Helicobacter pylori ( H. pylori ) is a pathogen that can remain in the stomach of an infected person for their entire life. As a result, this leads to the development of severe gastric diseases such as gastric cancer. In addition, current therapies have several problems including antibiotics resistance. Therefore, new practical options to eliminate this bacterium, and its induced affections, are required to avoid morbidity and mortality worldwide. One strategy in the search for new drugs is to detect compounds that inhibit a limiting step in a central metabolic pathway of the pathogen of interest. In this work, we tested 55 compounds to gain insights into their possible use as new inhibitory drugs of H. pylori glucose-6-phosphate dehydrogenase (HpG6PD) activity. The compounds YGC-1 ; MGD-1, MGD-2; TDA-1 ; and JMM-3 with their respective scaffold 1,3-thiazolidine-2,4-dione; 1H -benzimidazole; 1,3-benzoxazole, morpholine, and biphenylcarbonitrile showed the best inhibitory activity (IC 50 = 310, 465, 340, 204 and 304 μM, respectively). We then modeled the HpG6PD protein by homology modeling to conduct an in silico study of the chemical compounds and discovers its possible interactions with the HpG6PD enzyme. We found that compounds can be internalized at the NADP + catalytic binding site. Hence, they probably exert a competitive inhibitory effect with NADP + and a non-competitive or uncompetitive effect with G6P, that of the compounds binding far from the enzyme's active site. Based on these findings, the tested compounds inhibiting HpG6PD represent promising novel drug candidates against H. pylori .

An evaluation of antioxidant and anticancer activity was screened in Leptocarpha rivularis DC flower extracts using four solvents ( n -hexane (Hex), dichloromethane (DCM), ethyl acetate (AcOEt), and ethanol (EtOH)). Extracts were compared for total extract flavonoids and phenol contents, antioxidant activity (2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH), ferric reducing antioxidant potential (FRAP), total reactive antioxidant properties (TRAP) and oxygen radical absorbance capacity (ORAC)) across a determined value of reduced/oxidized glutathione (GSH/GSSG), and cell viability (the sulforhodamine B (SRB) assay). The most active extracts were analyzed by chromatographic analysis (GC/MS) and tested for apoptotic pathways. Extracts from Hex, DCM and AcOEt reduced cell viability, caused changes in cell morphology, affected mitochondrial membrane permeability, and induced caspase activation in tumor cell lines HT-29, PC-3, and MCF-7. These effects were generally less pronounced in the HEK-293 cell line (nontumor cells), indicating clear selectivity towards tumor cell lines. We attribute likely extract activity to the presence of sesquiterpene lactones, in combination with other components like steroids and flavonoids.

The purpose of this study was to explore how parents of children with neuromotor disorders in the department of Chuquisaca (Bolivia) perceive attendance to a physical therapy stimulation program and the expectations they place on the therapy and professional care provided to their children. Semi-structured interviews were conducted with the parents, related to their role in supporting the recommended exercise program for the child, generating topics such as benefits of the therapy for the child, impact on the family, and role of the project in terms of therapy and the physical therapists providing treatment, including both positive and negative aspects of the overall process. This study revealed the importance of understanding the feelings of families receiving intervention under a pioneering program in Bolivia for the detection and treatment of children with neuromotor disorders. Being able to access these types of services provides them with extensive personal, social, and economic support. Knowing their concerns, desires, and demands will allow us to continue to improve and offer the best care for children and families. The professionals involved should also be encouraged to develop effective teaching techniques to promote the inclusion of parents in the stimulation program.

Health Science students in Spain and Bolivia should be trained in the management of the processes of death and dying of patients. The aim of this study was to examine the degree of training, self-perceived safety and preferences in relation to the care of terminal and non-terminal patients. It was a descriptive, cross-sectional, multicenter study with students of Medicine, Nursing and Physiotherapy in Spain and Bolivia. The following variables were evaluated: care preparation and emotional preparation to caring for terminally ill and non-terminally ill patients, the Death Attitude Profile Revised (PAM-R) and the Bugen Scale for Facing Death. The self-perceived preparation of students for caring for terminally ill patients can be considered "fair" (mean 2.15, SD 0.756), and this was also the case for their perceived emotional preparation (mean 2.19, SD 0.827). In contrast, the score obtained for their preparedness for treating non-terminal patients was higher (mean 2.99 and 3.16, respectively). Working with terminally ill patients, including terminal or geriatric cancer patients, was the least preferred option among future health professionals. The results obtained show a limited preference for end-of-life care and treatment, highlighting a lack of preparation and motivation among health science students in Spain and Bolivia for working with these patients., Competing Interests: The authors declare no conflicts of interest.

Children in situations of destitution who become institutionalized commonly display developmental disorders, including delayed growth. The aim was to evaluate the environmental quality of the casas cuna of the Department of Chuquisaca (Plurinational state of Bolivia) in children aged 0 to 2 years old after receiving an early stimulation program based on psychomotor therapy. Thirty-six children who were institutionalized at shelter homes in the Department of Chuquisaca were selected to receive sessions of psychomotricity over a five-month period. The Infant/Toddler Home Observation for Measurement of the Environment (IT-HOME) scale and the Attachment During Stress Scale (ADS) were used. The adult-child relationship with factors of responsiveness (-0.89; p = 0.037), acceptance (0.57; p = 0.024), organization (-1.03; p < 0.001), learning material (-2.57; p < 0.001) and involvement (-1.92; p < 0.001) scored below expectations, showing that environmental indicators are a poor stimulation for children growing up in shelter homes. Improvements were found in the children's development after receiving this therapy. In conclusion, an early stimulation program based on psychomotor therapy over five months provided favorable results for the acquisition of skills for communication, motor development and social skills, which positively affect the psychomotor development.

Cancer cells exhibit exacerbated metabolic activity to maintain their accelerated proliferation and microenvironmental adaptation in order to survive under nutrient-deficient conditions. Tumors display an increase in glycolysis, glutaminolysis and fatty acid biosynthesis, which provide their energy source. Glutamine is critical for fundamental cellular processes, where intermediate metabolites produced through glutaminolysis are necessary for the maintenance of mitochondrial metabolism. These include antioxidants to remove reactive oxygen species, and the generation of the nonessential amino acids, purines, pyrimidines and fatty acids required for cellular replication and the activation of cell signaling. Some cancer cells are highly dependent on glutamine consumption since its catabolism provides an anaplerotic pathway to feed the Krebs cycle. Intermediate members of the glutaminolysis pathway have been found to be deregulated in several types of cancers and have been proposed as therapeutic targets and prognostic biomarkers. This review summarizes the main players in the glutaminolysis pathway, how they have been found to be deregulated in cancer and their implications for cancer maintenance. Furthermore, non-coding RNAs are now recognized as new participants in the regulation of glutaminolysis; therefore, their involvement in glutamine metabolism in cancer is discussed in detail.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most frequent human enzymopathy, affecting over 400 million people globally. Worldwide, 217 mutations have been reported at the genetic level, and only 19 have been found in Mexico. The objective of this work was to contribute to the knowledge of the function and structure of three single natural variants (G6PD A+, G6PD San Luis Potosi, and G6PD Guadalajara) and a double mutant (G6PD Mount Sinai), each localized in a different region of the three-dimensional (3D) structure. In the functional characterization of the mutants, we observed a decrease in specific activity, protein expression and purification, catalytic efficiency, and substrate affinity in comparison with wild-type (WT) G6PD. Moreover, the analysis of the effect of all mutations on the structural stability showed that its presence increases denaturation and lability with temperature and it is more sensible to trypsin digestion protease and guanidine hydrochloride compared with WT G6PD. This could be explained by accelerated degradation of the variant enzymes due to reduced stability of the protein, as is shown in patients with G6PD deficiency.

Induction motors are essential and widely used components in many industrial processes. Although these machines are very robust, they are prone to fail. Nowadays, it is a paramount task to obtain a reliable and accurate diagnosis of the electric motor health, so that a subsequent reduction of the required time and repairing costs can be achieved. The most common approaches to accomplish this task are based on the analysis of currents, which has some well-known drawbacks that may lead to false diagnosis. With the new developments in the technology of the sensors and signal processing field, the possibility of combining the information obtained from the analysis of different magnitudes should be explored, in order to achieve more reliable diagnostic conclusions, before the fault can develop into an irreversible damage. This paper proposes a smart-sensor that explores the weighted analysis of the axial, radial, and combination of both stray fluxes captured by a low-cost, easy setup, non-invasive, and compact triaxial stray flux sensor during the start-up transient through the short time Fourier transform (STFT) and characterizes specific patterns appearing on them using statistical parameters that feed a feature reduction linear discriminant analysis (LDA) and then a feed-forward neural network (FFNN) for classification purposes, opening the possibility of offering an on-site automatic fault diagnosis scheme. The obtained results show that the proposed smart-sensor is efficient for monitoring and diagnosing early induction motor electromechanical faults. This is validated with a laboratory induction motor test bench for individual and combined broken rotor bars and misalignment faults.

Air pollution has been recognized as a global health problem, causing around 7 million deaths worldwide and representing one of the highest environmental crises that we are now facing. Close to 30% of new lung cancer cases are associated with air pollution, and the impact is more evident in major cities. In this review, we summarize and discuss the evidence regarding the effect of particulate matter (PM) and its impact in carcinogenesis, considering the "hallmarks of cancer" described by Hanahan and Weinberg in 2000 and 2011 as a guide to describing the findings that support the impact of particulate matter during the cancer continuum.

Head and neck cancer (HNC) is the sixth cause of cancer-related death worldwide. Head and neck squamous cells carcinoma (HNSCC) is the most frequent subtype of HNC. The development of HNSCC is associated to alcohol consumption, smoking or infection by high-risk human Papillomavirus (HR-HPV). Although the incidence of cancers associated with alcohol and tobacco has diminished, HNSCC associated with HR-HPV has significantly increased in recent years. However, HPV-positive HNSCC responds well to treatment, which includes surgery followed by radiation or chemoradiation therapy. Radiation therapy (RT) is based on ionizing radiation (IR) changing cell physiology. IR can directly interact with deoxyribonucleic acid (DNA) or produce reactive oxygen and nitrogen species (RONS), provoking DNA damage. When DNA damage is not repaired, programmed cell death (apoptosis and/or autophagy) is induced. However, cancer cells can acquire resistance to IR avoiding cell death, where reprogramming of energy metabolism has a critical role and is intimately connected with hypoxia, mitochondrial physiology, oxidative stress (OS) and autophagy. This review is focused on the reprogramming of energy metabolism in response to RT in HPV-positive and HPV-negative HNSCC, showing their differences in cellular metabolism management and the probable direction of treatments for each subtype of HNSCC.

By using earthquake catalogs, previous studies have reported evidence that some changes in the spatial and temporal organization of earthquake activity are observed before and after of a main shock. These previous studies have used different approaches for detecting clustering behavior and distance-events density in order to point out the asymmetric behavior of foreshocks and aftershocks. Here, we present a statistical analysis of the seismic activity related to the M w = 8.2 earthquake that occurred on 7 September 2017 in Mexico. First, we calculated the inter-event time and distance between successive events for the period 1 January 1998 until 20 October 2017 in a circular region centered at the epicenter of the M w = 8.2 EQ. Next, we introduced the concept of pseudo-velocity as the ratio between the inter-event distance and inter-event time. A sliding window is considered to estimate some statistical features of the pseudo-velocity sequence before the main shock. Specifically, we applied the multifractal method to detect changes in the spectrum of singularities for the period before the main event on 7 September. Our results point out that the multifractality associated with the pseudo-velocities exhibits noticeable changes in the characteristics of the spectra (more narrower) for approximately three years, from 2013 until 2016, which is preceded and followed by periods with wider spectra. On the other hand, we present an analysis of patterns of seismic quiescence before the M w = 8.2 earthquake based on the Schreider algorithm over a period of 27 years. We report the existence of an important period of seismic quietude, for six to seven years, from 2008 to 2015 approximately, known as the alpha stage, and a beta stage of resumption of seismic activity, with a duration of approximately three years until the occurrence of the great earthquake of magnitude M w = 8.2 . Our results are in general concordance with previous results reported for statistics based on magnitude temporal sequences.

CFH and HTRA1 genes are traditional markers of increased risk of age-related macular degeneration (AMD) across populations. Recent findings suggest that additional genes-for instance, in the dystrophin-associated protein complex-might be promising markers for AMD. Here, we performed a case-control study to assess the effect of SGCD single nucleotide polymorphisms (SNPs), a member of this protein family, on AMD diagnosis and phenotype. We performed a case-control study of an under-studied population from Hispanics in Mexico City, with 134 cases with 134 unpaired controls. Cases were 60 years or older (Clinical Age-Related Maculopathy Staging (CARMS) grade 4⁻5, as assessed by experienced ophthalmologists following the American Association of Ophthalmology (AAO) guidelines), without other retinal disease or history of vitreous-retinal surgery. Controls were outpatients aged 60 years or older, with no drusen or retinal pigment epithelium (RPE) changes on a fundus exam and a negative family history of AMD. We examined SNPs in the SGCD gene (rs931798, rs140617, rs140616, and rs970476) by sequencing and real-time PCR. Genotyping quality checks and univariate analyses were performed with PLINK v1.90b3.42. Furthermore, logistic regression models were done in SAS v.9.4 and haplotype configurations in R v.3.3.1. After adjusting for clinical covariates, the G/A genotype of the SGCD gene (rs931798) significantly increases the odds of being diagnosed with AMD in 81% of cases (1.81; 95% CI 1.06⁻3.14; p = 0.031), especially the geographic atrophy phenotype (1.82; 95% CI 1.03⁻3.21; p = 0.038) compared to the G/G homozygous genotype. Moreover, the GATT haplotype in this gene (rs931798, rs140617, rs140616, and rs970476) is associated with lower odds of AMD (adjusted odds ratio (OR) 0.13; 95% CI 0.02⁻0.91; p = 0.041). SGCD is a promising gene for AMD research. Further corroboration in other populations is warranted, especially among other Hispanic ethnicities., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; final the writing of the manuscript; or in the decision to publish the results.

The alteration of glucose metabolism is one of the first biochemical characteristics associated with cancer cells since most of these cells increase glucose consumption and glycolytic rates even in the presence of oxygen, which has been called &ldquo;aerobic glycolysis” or the Warburg effect. Human papillomavirus (HPV) is associated with approximately 5% of all human cancers worldwide, principally to cervical cancer. E6 and E7 are the main viral oncoproteins which are required to preserve the malignant phenotype. These viral proteins regulate the cell cycle through their interaction with tumor suppressor proteins p53 and pRB, respectively. Together with the viral proteins E5 and E2, E6 and E7 can favor the Warburg effect and contribute to radio- and chemoresistance through the increase in the activity of glycolytic enzymes, as well as the inhibition of the Krebs cycle and the respiratory chain. These processes lead to a fast production of ATP obtained by Warburg, which could help satisfy the high energy demands of cancer cells during proliferation. In this way HPV proteins could promote cancer hallmarks. However, it is also possible that during an early HPV infection, the Warburg effect could help in the achievement of an efficient viral replication.

To investigate the anti- Saprolegnia activities of chalconic compounds, nine dialkoxychalcones 2 ⁻ 10 , along with their key building block 2',4'-dihydroxychalcone 1 , were evaluated for their potential oomycide activities against Saprolegnia australis strains. The synthesis afforded a series of O -alkylated derivatives with typical chalcone skeletons. Compounds 4 ⁻ 10 were reported for the first time. Interestingly, analogue 8 with the new scaffold demonstrated remarkable in vitro growth-inhibitory activities against Saprolegnia strains, displaying greater anti-oomycete potency than the standard drugs used in the assay, namely fluconazole and bronopol. In contrast, a dramatic loss of activity was observed for O -alkylated derivatives 2 , 3 , 6 , and 7 . These findings have highlighted the therapeutic potential of the natural compound 1 scaffold to be exploitable as a drug lead with specific activity against various Saprolegnia strains.

Persistent infections with high-risk human papillomavirus (HPV) constitute the main risk factor for cervical cancer development. HPV16 is the most frequent type associated to squamous cell carcinomas (SCC), followed by HPV18. The long control region (LCR) in the HPV genome contains the replication origin and sequences recognized by cellular transcription factors (TFs) controlling viral transcription. Altered expression of E6 and E7 viral oncogenes, modulated by the LCR, causes modifications in cellular pathways such as proliferation, leading to malignant transformation. The aim of this study was to identify specific TFs that could contribute to the modulation of high-risk HPV transcriptional activity, related to the cellular histological origin. We identified sex determining region Y (SRY)-box 2 (SOX2) response elements present in HPV16-LCR. SOX2 binding to the LCR was demonstrated by in vivo and in vitro assays. The overexpression of this TF repressed HPV16-LCR transcriptional activity, as shown through reporter plasmid assays and by the down-regulation of endogenous HPV oncogenes. Site-directed mutagenesis revealed that three putative SOX2 binding sites are involved in the repression of the LCR activity. We propose that SOX2 acts as a transcriptional repressor of HPV16-LCR, decreasing the expression of E6 and E7 oncogenes in a SCC context.

Cerium oxide and mixed Cu/Ce oxide nanoparticles were prepared by the oil-in-water (O/W) microemulsion reaction method in mild conditions. The Cu/Ce molar ratio was varied between 0/100 and 50/50. According to X-ray diffraction (XRD), below 30/70 Cu/Ce molar ratio, the materials presented a single phase consistent with cubic fluorite CeO₂. However, above Cu/Ce molar ratio 30/70, an excess monoclinic CuO phase in coexistence with the predominant Cu/Ce mixed oxide was detected by XRD and High-Resolution Transmission Electron Microscopy (HRTEM). Raman spectroscopy showed that oxygen vacancies increased significantly as the Cu content was increased. Band gap ( E g ) was investigated as a function of the Cu/Ce molar ratio, resulting in values from 2.91 eV for CeO₂ to 2.32 eV for the mixed oxide with 30/70 Cu/Ce molar ratio. These results indicate that below 30/70 Cu/Ce molar ratio, Cu 2+ is at least partially incorporated into the ceria lattice and very well dispersed in general. In addition, the photodegradation of Indigo Carmine dye under visible light irradiation was explored for selected samples; it was shown that these materials can remove such contaminants, either by adsorption and/or photodegradation. The results obtained will encourage investigation into the optical and photocatalytic properties of these mixed oxides, for widening their potential applications.

Leukemic stem cells (LSCs) are defined as cells that possess the ability to self-renew and give rise to the differentiated cancer cells that comprise the tumor. These LSCs seem to show chemo-resistance and radio-resistance leading to the failure of conventional cancer therapies. Current therapies are directed at the fast growing tumor mass leaving the LSC fraction untouched. Eliminating LSCs, the root of cancer origin and recurrence, is considered to be a hopeful approach to improve survival or even to cure cancer patients. In order to achieve this, the characterization of LSCs is a prerequisite in order to develop LSC-based therapies to eliminate them. Here we review if vitamin D analogues may allow an avenue to target the LSCs.

Aqueous and ethanolic extracts obtained from nine Chilean marine macro-algae collected at different seasons were examined in vitro and in vivo for properties that reduce the growth of plant pathogens or decrease the injury severity of plant foliar tissues following pathogen infection. Particular crude aqueous or organic extracts showed effects on the growth of pathogenic bacteria whereas others displayed important effects against pathogenic fungi or viruses, either by inhibiting fungal mycelia growth or by reducing the disease symptoms in leaves caused by pathogen challenge. Organic extracts obtained from the brown-alga Lessonia trabeculata inhibited bacterial growth and reduced both the number and size of the necrotic lesion in tomato leaves following infection with Botrytis cinerea. Aqueous and ethanolic extracts from the red-alga Gracillaria chilensis prevent the growth of Phytophthora cinnamomi, showing a response which depends on doses and collecting-time. Similarly, aqueous and ethanolic extracts from the brown-alga Durvillaea antarctica were able to diminish the damage caused by tobacco mosaic virus (TMV) in tobacco leaves, and the aqueous procedure is, in addition, more effective and seasonally independent. These results suggest that macro-algae contain compounds with different chemical properties which could be considered for controlling specific plant pathogens.