Assessing the effectiveness of international government responses to the COVID-19 pandemic.

This paper examines the effectiveness of non-pharmaceutical measures adopted by governments to control the evolution of the COVID-19 pandemic. Using a Panel VAR model for the OECD countries, we test for Granger causality between the 7-day cumulative incidence, mortality rate, and government response indexes. Granger-type statistics reveal evidence that the evolution of the COVID-19 pandemic influenced the measures taken by governments. However, limited or nonexistent evidence supports the reverse situation. This suggests that government measures were not highly effective in controlling the pandemic. While not implying total ineffectiveness, our results indicate a considerable lack of efficacy, emphasizing a lesson for governments to learn from and correct in preparation for similar events in the future.

Cognitive Patterns and Problematic Use of Video Games in Adolescents: A Cluster Analysis.

BACKGROUND: Video game playing (VGP) is an increasingly common leisure activity among children and adolescents, although in some cases, it is accompanied by problems due to misuse. METHOD: A sample of 2884 children and adolescents aged between 12 and 20, representative of the Community of Madrid (Spain), were studied using a cluster analysis to explore the existence of cognitive patterns associated with engagement, attitudes, and concurrent cognitions. We also explored the relationship between these patterns and problematic VGP, using the 2173 gamers as a reference. RESULTS: The concurrent cognitions were not qualitatively different between the problematic users and the others. High engagement and high activation of concurrent cognitions (intensity and frequency) showed the greatest relationship with problematic VGP. CONCLUSIONS: The results suggest the existence of different groups of gamers and the relevance to include psycho-educational aspects in intervention programs, as well as the training of specific skills, especially those related with the control of activation. Limitations related to the sample size and potential supplementary analyses are acknowledged.

Whole-Genome Doubling as a source of cancer: how, when, where, and why?

Chromosome instability is a well-known hallmark of cancer, leading to increased genetic plasticity of tumoral cells, which favors cancer aggressiveness, and poor prognosis. One of the main sources of chromosomal instability are events that lead to a Whole-Genome Duplication (WGD) and the subsequently generated cell polyploidy. In recent years, several studies showed that WGD occurs at the early stages of cell transformation, which allows cells to later become aneuploid, thus leading to cancer progression. On the other hand, other studies convey that polyploidy plays a tumor suppressor role, by inducing cell cycle arrest, cell senescence, apoptosis, and even prompting cell differentiation, depending on the tissue cell type. There is still a gap in understanding how cells that underwent WGD can overcome the deleterious effect on cell fitness and evolve to become tumoral. Some laboratories in the chromosomal instability field recently explored this paradox, finding biomarkers that modulate polyploid cells to become oncogenic. This review brings a historical view of how WGD and polyploidy impact cell fitness and cancer progression, and bring together the last studies that describe the genes helping cells to adapt to polyploidy.

Correlation between the Altered Gut Microbiome and Lifestyle Interventions in Chronic Widespread Pain Patients: A Systematic Review.

Background: Lifestyle interventions have a direct impact on the gut microbiome, changing its composition and functioning. This opens an innovative way for new therapeutic opportunities for chronic widespread patients. Purpose: The goal of the present study was to evaluate a correlation between lifestyle interventions and the gut microbiome in patients with chronic widespread pain (CWP). Methods: The systematic review was conducted until January 2023. Pain and microbiome were the two keywords selected for this revision. The search was conducted in PubMed, Chochrane, PEDro and ScienceDirect, where 3917 papers were obtained. Clinical trials with lifestyle intervention in CWP patients were selected. Furthermore, these papers had to be related with the gut microbiome, excluding articles related to other types of microbiomes. Results: Only six articles were selected under the eligibility criteria. Lifestyle interventions were exercise, electroacupuncture and ingesting a probiotic. Conclusions: Lifestyle intervention could be a suitable choice to improve the gut microbiome. This fact could be extrapolated into a better quality of life and lesser levels of pain.

PFOA-Induced Ovotoxicity Differs Between Lean and Obese Mice With Impacts on Ovarian Reproductive and DNA Damage Sensing and Repair Proteins.

Perfluorooctanoic acid (PFOA) is an environmentally persistent perfluoroalkyl substance that is widely used in consumer products. Exposure to PFOA is associated with reproductive and developmental effects including endocrine disruption, delayed puberty in girls, and decreased fetal growth. In the United States, obesity affects 40% of women and 20% of girls, with higher rates in minority females. Obesity causes infertility, poor oocyte quality, miscarriage, and offspring defects. This study proposed that PFOA exposure would impact estrous cyclicity, ovarian steroid hormones, and the ovarian proteome and further hypothesized that obesity would impact PFOA-induced ovotoxicity. Female wild type (KK.Cg-a/a; lean) or KK.Cg-Ay/J mice (obese) received saline (CT) or PFOA (2.5 mg/kg) per os for 15 days beginning at 7 weeks of age. There were no effects on food intake, body weight, estrous cyclicity, serum progesterone, and heart, spleen, kidney, or uterus weight (p > .05). Ovary weight was decreased (p < .05) by PFOA exposure relative to vehicle control-treated mice in lean but not obese mice. Liquid chromatography-tandem mass spectrometry was performed on isolated ovarian protein and PFOA exposure altered the ovarian abundance of proteins involved in DNA damage sensing and repair pathways and reproduction pathways (p < .05) differentially in lean and obese mice. The data suggest that PFOA exposure alters ovary weight and differentially targets ovarian proteins in lean and obese females in ways that might reduce female fecundity.

Association between Sleep Disorders and Sleep Quality in Patients with Temporomandibular Joint Osteoarthritis: A Systematic Review.

BACKGROUND: Osteoarthritis (OA) is a leading cause of disability, the most common form of chronic disease in the temporomandibular joint (TMJ), and the most severe disease type of temporomandibular disorders (TMD). The etiology of TMD is multifactorial, considering parafunctional habits, sleep bruxism, or sleep disturbance as common factors. Insomnia and apnea are the two most frequent forms of sleep disorders in TMD patients. Due to this, the objective of this systematic review was to highlight whether there is currently scientific evidence in the literature describing that patients with temporomandibular joint osteoarthritis (TMJ-OA) are associated with increased sleep disorders or impaired sleep quality. METHODS: This systematic review was completed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) statement and was registered with PROSPERO prior to completion of the main search. Original observational studies that analyze the association of sleep disorders and sleep quality in patients with TMJ-OA were included in the present review. RESULTS: 770 studies were screened by abstract and title according to inclusion and exclusion criteria, and finally, 7 articles were included in the qualitative synthesis and a total of 772 patients diagnosed with TMJ-OA. CONCLUSIONS: There is insufficient evidence to indicate that patients with TMJ OA are associated with increased sleep disorders or poorer sleep quality.

Environmental and occupational exposure to metals (manganese, mercury, iron) and Parkinson's disease in low and middle-income countries: a narrative review.

OBJECTIVES: We designed and conducted a narrative review consistent with the PRISMA guidelines (PROSPERO registration number: CRD42018099498) to evaluate the association between environmental metals (manganese, mercury, iron) and Parkinson's Disease (PD) in low and middle-income countries (LMIC). METHODS: Data sources: A total of 19 databases were screened, and 2,048 references were gathered. Study selection: Randomized controlled trials, cluster trials, cohort studies, case-control studies, nested case-control studies, ecological studies, cross-sectional studies, case series, and case reports carried out in human adults of LMIC, in which the association between at least one of these three metals and the primary outcome were reported. Data extraction: We extracted qualitative and quantitative data. The primary outcome was PD cases, defined by clinical criteria. A qualitative analysis was conducted. RESULTS: Fourteen observational studies fulfilled the selection criteria. Considerable variation was observed between these studies' methodologies for the measurement of metal exposure and outcome assessment. A fraction of studies suggested an association between the exposure and primary outcome; nevertheless, these findings should be weighted and appraised on the studies' design and its implementation limitations, flaws, and implications. CONCLUSIONS: Further research is required to confirm a potential risk of metal exposure and its relationship to PD. To our awareness, this is the first attempt to evaluate the association between environmental and occupational exposure to metals and PD in LMIC settings using the social determinants of health as a framework.

Inequality in the Face of Death: The Income Gradient in Mortality of the Spanish Pre-Recession Working-Age Population.

The purpose of this paper is to evaluate the association between socioeconomic status (SES) and mortality over a three-year period for working-age Spaniards (2007-2009), paying particular attention to the effect of income level. The analysis is relatively new in Spain, and the studies are limited. Neither income nor wealth are included in existing Spanish mortality studies. The main reason for this limitation is the nature of the data sets used, mainly Census Records. We overcome this problem by using data on 693,994 individuals taken from a Social Security sampling and used to estimate the probabilities of death for each income decile and the mortality rate ratios in three different models: (1) using only income, controlled by age and sex, (2) adding socio-economic and geographical variables, and (3) adding level of education. However, the data used here also have some limitations. They do not include government employees, the military or the Department of Justice personnel, whose exclusion we believe causes an under-representation of highly educated people in our sample. The results confirm that there is a non-linear relationship between mortality and income. This non-linear relationship implies that income redistribution resulting from progressive taxation systems could lead to higher reductions in mortality for low-income groups than the reductions induced in the mortality of the high-income population, thus reducing overall mortality.

Exposición de jóvenes y adolescentes a la publicidad de los juegos de azar: una revisión sistemática / Exposure of adolescents and youth to Gambling advertising: a sys-tematic review

Los posibles efectos negativos de la publicidad de juegos de azar (JdA), sobre todo en Adolescentes y Jóvenes (AyJ), generan alarma social. Se realizó una revisión sistemática de las investigaciones sobre publicidad y juego en AyJ, en los últimos 10 años, siguiendo las directrices PRISMA, seleccionándose 31 trabajos. Los resultados destacan que AyJ, en contra de la legislación, participan con frecuencia en JdA, presentando problemas de juego. La publicidad de JdA es variada e intensa en especial en TV, eventos deportivos y redes sociales, estando dirigida a JyA, aunque suelen ser críticos con ella. Afecta más a varones jóvenes y con conductas de juego inadecuadas, consolidándolas. Los contenidos principales tratan de normalizar el juego y resaltar ganancias (sociales o económicas). El nivel de recuerdo y las actitudes sobre la publicidad del juego se asocian a incrementos en la intención de jugar, comportamientos de juego, y problemas de juego. Los incentivos más eficaces para jugar incluyen promociones económicas. La publicidad parece tener efecto, aunque reducido, para mejorar la actitud hacia los JdA e incrementar la participación en éstos, pero es difícil identificar sus efectos a medio y largo plazo. Son necesarios más estudios sobre JdA y publicidad, en especial en España

The possible negative effects of gambling Advertising (GA), especially in Adolescents and Youth (A&Y), generate social alarm. A systematic review of the research on advertising and gambling in A&Y in the last 10 years was carried out, following the PRISMA guidelines, including 31 studies. The results highlight that A&Y, against the law, frequently participate in gambling, with some having gambling problems. GA is varied and intense, especially on TV, sporting events and social networks, also targeting A&Y, although they are often critical of it. It affects more young men and people with inappropriate gambling behaviours, consolidating those behaviours. The main messages try to normalise gambling and highlight profits (social or economic). The levels of recall, as well as the attitudes about GA are associated with an increase in gambling intentions, behaviours, and problems. The most effective incentives to gamble include economic promotions. Advertising seems to have an effect, albeit reduced, to improve the attitude towards gambling and increase participation, but it is difficult to identify its effects in the medium and long term. More studies on gambling and advertising are necessary, especially in Spain

Global Trends in Child Obesity: Are Figures Converging?

Childhood obesity has become one of the most serious global health challenges of our time. The combined prevalence of overweight and obesity has rapidly increased worldwide during the last two decades, especially in some developing countries where obesity is reaching levels on a par with some industrialized countries, or even higher. This fast growth has occurred especially in countries in the midst of rapid social-economic transitions. Most international comparisons focus on the adult population while analyses focusing on the child population are more limited. Using the methodology developed by Phillips and Sul, this paper studies the worldwide evolution of children's body mass index (BMI), overweight and obesity prevalence for a large sample of countries during the period 1975-2016. Our results indicate that the figures for BMI or the prevalence of obesity in different countries do not converge, while the opposite is the case for overweight prevalence in children. Furthermore, there is a non-linear relationship between obesity and income or human capital, indicating that low and middle-income countries require a strong initiative for health policies targeting obesity prevention.

Remodeling of the Microvasculature: May the Blood Flow Be With You.

The vasculature ensures optimal delivery of nutrients and oxygen throughout the body, and to achieve this function it must continually adapt to varying tissue demands. Newly formed vascular plexuses during development are immature and require dynamic remodeling to generate well-patterned functional networks. This is achieved by remodeling of the capillaries preserving those which are functional and eliminating other ones. A balanced and dynamically regulated capillary remodeling will therefore ensure optimal distribution of blood and nutrients to the tissues. This is particularly important in pathological contexts in which deficient or excessive vascular remodeling may worsen tissue perfusion and hamper tissue repair. Blood flow is a major determinant of microvascular reshaping since capillaries are pruned when relatively less perfused and they split when exposed to high flow in order to shape the microvascular network for optimal tissue perfusion and oxygenation. The molecular machinery underlying blood flow sensing by endothelial cells is being deciphered, but much less is known about how this translates into endothelial cell responses as alignment, polarization and directed migration to drive capillary remodeling, particularly in vivo. Part of this knowledge is theoretical from computational models since blood flow hemodynamics are not easily recapitulated by in vitro or ex vivo approaches. Moreover, these events are difficult to visualize in vivo due to their infrequency and briefness. Studies had been limited to postnatal mouse retina and vascular beds in zebrafish but new tools as advanced microscopy and image analysis are strengthening our understanding of capillary remodeling. In this review we introduce the concept of remodeling of the microvasculature and its relevance in physiology and pathology. We summarize the current knowledge on the mechanisms contributing to capillary regression and to capillary splitting highlighting the key role of blood flow to orchestrate these processes. Finally, we comment the potential and possibilities that microfluidics offers to this field. Since capillary remodeling mechanisms are often reactivated in prevalent pathologies as cancer and cardiovascular disease, all this knowledge could be eventually used to improve the functionality of capillary networks in diseased tissues and promote their repair.

Evaluation of Fetal Lung Maturity by Quantitative Analysis (quantusFLM) in Women with Gestational Diabetes Mellitus.

OBJECTIVES: The aim of the present study was to evaluate fetal lung maturity using the noninvasive method of quantitative ultrasound analysis of fetal lung texture (quantusFLM) in women with gestational diabetes mellitus (GDM). METHODS: A total of 96 women at 36-38 weeks of gestation were enrolled. They were classified as follows: 33 GDM cases treated with diet, 30 GDM cases treated with diet plus insulin, and 33 normoglycemic women (control group). A quantitative analysis of lung texture was performed. RESULTS: There were significant differences in the lung maturity results among groups (p = 0.004). These differences were established between the insulin-treated group of patients and both the control (p = 0.006) and diet-only (p = 0.003) groups. While none of the women in the control group or in the diet group had a high risk of immaturity, 16.7% of those treated with insulin (5/30) did (p = 0.003). There was no statistically significant correlation between HbA1c and the result of the test. CONCLUSIONS: Quantitative ultrasound study of fetal lung texture suggests that a significant percentage of pregnant women with GDM treated with insulin had fetal lung immaturity in the late preterm to early term.

Attomolar quantitation of Mycobacterium tuberculosis by asymmetric helicase-dependent isothermal DNA-amplification and electrochemical detection.

A highly sensitive and robust method for the quantification of specific DNA sequences based on coupling asymmetric helicase-dependent DNA amplification to electrochemical detection is described. This method relies on the entrapment of the amplified ssDNA sequences on magnetic beads followed by a post-amplification hybridization assay to provide an added degree of specificity. As a proof-of-concept a 84-bases long sequence specific of Mycobacterium tuberculosis is amplified at 65°C, providing 3×10(6) amplification after 90 min. Using this system 0.5 aM, corresponding to 15 copies of the target gene in 50 µL of sample, can be successfully detected and reliably quantified under isothermal conditions in less than 4h. The assay has been applied to the detection of M. tuberculosis in sputum, pleural fluid and urine samples. Besides this application, the proposed assays is a powerful and general tool for molecular diagnostic that can be applied to the detection of other specific DNA sequences, taking full advantage of the plethora of genomic information now available.

A fluorescence-based supramolecular tandem assay for monitoring lysine methyltransferase activity in homogeneous solution.

The demand for practical and convenient enzyme assays for histone lysine methyltransferases (HKMTs) emerges along with the rapid development of this young class of enzymes. A supramolecular reporter pair composed of p-sulfonatocalix[4]arene (CX4) and the fluorescent dye lucigenin (LCG) has been used to monitor enzymatic trimethylation of lysine residues in peptide substrates. The assay affords a switch-ON fluorescence response and operates in a continuous, real-time, and label-free fashion. The underlying working principle relies on the higher affinity of the macrocycle towards the trimethylated product of the enzymatic reaction as compared to the substrate, which allows the assay to be carried out in the product-selective mode. The final product incorporates a trimethylammonium moiety, a known high-affinity binding motif for CX4. Two substrates corresponding to the H3 N-terminal tail, namely, S2 (RTKQTARKSTGGKAP) and S6 (QTARKSTGGS), were selected as model compounds for methylation with the Neurospora crassa Dim-5 enzyme and investigated by the newly developed supramolecular tandem HKMTs assay. Only the longer substrate S2 underwent methylation in solution. The potential of the assay for inhibitor screening was demonstrated by means of inhibition studies with 1,10-phenanthroline to afford an inhibition constant of (70±20) µM.

Validation of the spanish version of the Multiple Sclerosis International Quality of Life (Musiqol) questionnaire.

BACKGROUND: The Multiple Sclerosis International Quality Of Life (MusiQoL) questionnaire, a 31-item, multidimensional, self-administrated questionnaire that is available in 14 languages including Spanish, has been validated using a large international sample. We investigated the validity and reliability of the Spanish version of MusiQoL in Spain. METHODS: Consecutive patients with different types and severities of multiple sclerosis (MS) were recruited from 22 centres across Spain. All patients completed the MusiQoL questionnaire, the 36-Item Short Form (SF-36) health survey, and a symptoms checklist at baseline and 21 days later. External validity, internal consistency, reliability and reproducibility were tested. RESULTS: A total of 224 Spanish patients were evaluated. Dimensions of MusiQoL generally demonstrated a high internal consistency (Cronbach's alpha: 0.70-0.92 for all but two MusiQoL domain scores). External validity testing revealed that the MusiQoL index score correlated significantly with all SF-36 dimension scores (Pearson's correlation: 0.46-0.76), reproducibility was satisfactory (intraclass correlation coefficient: 0.60-0.91), acceptability was high, and the time taken to complete the 31-item questionnaire was reasonable (mean [standard deviation]: 9.8 [11.8] minutes). CONCLUSIONS: The Spanish version of the MusiQoL questionnaire appears to be a valid and reliable instrument for measuring quality of life in patients with MS in Spain and constitutes a useful instrument to measure health-related quality of life in the clinical setting.

Thermodynamics of the dimer formation of 2(I),3(I)-O-(o-xylylene)-per-O-Me-gamma-cyclodextrin: fluorescence, molecular mechanics and molecular dynamics.

The thermodynamics of the dimer formation of 2(I),3(I)-O-(o-xylylene)-per-O-Me-gamma-cyclodextrin (XmgammaCD) in aqueous solution was studied by fluorescence techniques, Molecular Mechanics and Molecular Dynamics. Lifetime averages , obtained from fluorescence decay profiles upon excitation of the xylylene appended group, were used as the property sensitive to the association process. The dimerization equilibrium constants (K(D)) were obtained from non-linear regression analysis of the plots of against [XmgammaCD] at several temperatures and they were compared with the values obtained for the counterparts Xmalpha- and XmbetaCDs. The van't Hoff plot allows us to obtain the DeltaH and DeltaS showing that the dimerization process was also entropically disfavoured. Molecular Mechanics as well as Molecular Dynamics calculations in the presence of water were also employed to study the conformational behaviour of isolated XmgammaCDs, the possible structure of the dimers formed and the driving forces involved in such association processes. Results indicate that those conformations where Xy moiety does not block the cavity entrance are favoured. Dimers are preferably formed by head-to-head CD approaching. However, the formation of stable head-to-tail is not dismissed.

Fluorescence, induced circular dichroism and molecular mechanics of 1-methyl naphthalenecarboxylate complexes with 2-hydroxypropyl cyclodextrins.

Steady-state, time-resolved fluorescence, Circular Dichroism and Molecular Mechanics techniques were used to study the complexation of 1-methyl naphthalenecarboxylate (1MN) with the 2-hydroxylpropyl-alpha-, -beta- and -gammacyclodextrins (HPCDs). The emission spectrum of 1MN shows two bands whose intensity ratios (R) are sensitive to complexation. The stoichiometry, binding constants and thermodynamics parameters upon complexation were obtained from the variation of fluorescence intensity, R, and lifetime averages, [Formula: see text], with [HPCD] and temperature. They were then compared with the ones obtained for the complexation of 1MN with the non-substituted alpha-, beta- and gammaCDs. Like the 1MN:CD complexes, the 1MN:HPCD ones showed 1:1 stoichiometries, but they resulted relatively more stable. Molecular Mechanics calculations in the presence of water allowed us to understand the structure of the complexes and the possible driving forces responsible for the complexation. Geometry agrees with the experimental stoichiometry and the signs of enthalpy and entropy changes. R for the complexes, quenching, fluorescence depolarization measurements and induced circular dichroism spectra also supported the proposed structures.

Complexation of dimethyl 2,3-naphthalenedicarboxylate with 2-hydroxypropyl-alpha-, -beta- and -gamma-cyclodextrins in aqueous solution by fluorescence, circular dichroism and molecular mechanics.

Fluorescence, circular dichroism and molecular mechanics have been used to study the complexation of 2,3-dimethyl naphthalenedicarboxylate with 2-hydroxypropyl-alpha-, -beta and -gamma-cyclodextrins (HPCDs) in aqueous solution. Emission spectra upon excitation of the naphthalenedicarboxylate group show two bands whose intensity ratio R is quite sensitive to polarity. From the change of R and lifetimes averages with HPCD concentration and temperature were obtained the stoichiometry, the association constants and the enthalpy and entropy changes during the complexation. R, and the fluorescence anisotropies (r) extrapolated at [HPCD]-->infinity allows us to estimate the polarity and microviscosity of the media surrounding the guest when complexed. In addition, the analysis of quenching and induced circular dichroism experiments and molecular mechanics calculations in the presence of water, provide information about the forces responsible for the complexation and the geometry of the complexes.