Respiratory diseases in Mexico: analysis from the Global Burden of Disease study 2021.

BACKGROUND: Respiratory diseases (RD) are often analyzed separately rather than collectively, possibly leading to an underestimation of their total burden. OBJECTIVE: To analyze the burden of RD in Mexico for population aged 20 or older from 1990 to 2021. MATERIAL AND METHODS: We present the burden of RD in Mexico based on estimates of the Global Burden of Disease study for mortality and disability-adjusted life years (DALYs), comprising counts, rates per 100,000, as well as age-standardized rates. RDs were categorized into three key groups: chronic respiratory diseases (CRD), respiratory infections (RI), and respiratory cancers. RESULTS: In 2021, among those aged 20+, RDs were responsible for 336,728 deaths, which accounts for 30.5% of total deaths -a nearly threefold increase since 2019, primarily due to the COVID-19 pandemic. CRDs contributed with 3.4% of total deaths; RIs, with 25.9%; and respiratory cancers, with 1.2%. CRDs showed a continuous rise in deaths, crude mortality, and DALY rates across genders, with no signs of leveling. RD burden varied widely across Mexican states. Age-standardized CRD mortality rates have generally declined since 1990, except for interstitial lung diseases, which have consistently increased. CONCLUSION: The significant burden of mortality and disability due to RDs in Mexico underscores the n|ecessity for enhanced prevention, research, and for addressing risk factors such as smoking and pollution. Ongoing healthcare training can help reduce RD burden.

ANTECEDENTES: Las enfermedades respiratorias (ER) se analizan individualmente, posiblemente con subestimación de su carga total. OBJETIVO: Analizar la carga de las ER en México para población de 20 años o más de 1990 a 2021. MATERIAL Y MÉTODOS: Se presenta la carga de ER en México a partir de estimaciones del estudio Global Burden of Disease en cuanto a mortalidad y años de vida saludable (AVISA) perdidos que comprenden recuentos, tasas por 100 000 y tasas estandarizadas por edad. Las ER se categorizaron en enfermedades respiratorias crónicas (ERC), infecciones respiratorias y cánceres respiratorios. RESULTADOS: En 2021, las ER causaron la muerte de 336 728 adultos mayores de 20 años, lo que representó 30.5 % del total de defunciones, incremento cercano al triple respecto a 2019, principalmente debido a COVID-19. Las ERC contribuyeron con 3.4 % del total de muertes, las infecciones respiratorias con 25.9 % y los cánceres respiratorios con 1.2 %. La mortalidad y AVISA perdidos por ERC se incrementaron persistentemente, con variaciones entre los estados. Las tasas de mortalidad ajustadas por edad de las ERC disminuyeron desde 1990, excepto las enfermedades pulmonares intersticiales, que se incrementaron constantemente. CONCLUSIÓN: Los significativos niveles de mortalidad y discapacidad debidos a enfermedades respiratorias en México exigen mejorar la prevención, investigación y abordar factores de riesgo como tabaquismo y contaminación, además de fomentar la capacitación médica continua.

Optimization of Regioselective α-Glucosylation of Hesperetin Catalyzed by Cyclodextrin Glucanotransferase.

The regioselective α-glucosylation of hesperetin was achieved by a transglycosylation reaction catalyzed by cyclodextrin glucanotransferase (CGTase) from Thermoanaerobacter sp. using soluble starch as glucosyl donor. By combining mass spectrometry (ESI-TOF) and 2D-NMR analysis, the main monoglucosylated derivative was fully characterized (hesperetin 7-O-α-d-glucopyranoside). In order to increase the yield of monoglucoside, several reaction parameters were optimized: Nature and percentage of cosolvent, composition of the aqueous phase, glucosyl donor, temperature, and the concentrations of hesperetin and soluble starch. Under the optimal conditions, which included the presence of 30% of bis(2-methoxyethyl) ether as cosolvent, the maximum concentration of monoglucoside was approximately 2 mM, obtained after 24 h of reaction. To our knowledge, this is the first report of direct glucosylation of hesperetin employing free enzymes instead of whole cells.

Evolvability meets biogeography: evolutionary potential decreases at high and low environmental favourability.

Understanding and forecasting the effects of environmental change on wild populations requires knowledge on a critical question: do populations have the ability to evolve in response to that change? However, our knowledge on how evolution works in wild conditions under different environmental circumstances is extremely limited. We investigated how environmental variation influences the evolutionary potential of phenotypic traits. We used published data to collect or calculate 135 estimates of evolvability of morphological traits of European wild bird populations. We characterized the environmental favourability of each population throughout the species' breeding distribution. Our results suggest that the evolutionary potential of morphological traits decreases as environmental favourability becomes high or low. Strong environmental selection pressures and high intra-specific competition may reduce species' evolutionary potential in low- and high- favourability areas, respectively. This suggests that species may be least able to adapt to new climate conditions at their range margins and at the centre. Our results underscore the need to consider the evolutionary potential of populations when studying the drivers of species distributions, particularly when predicting the effects of environmental change. We discuss the utility of integrating evolutionary dynamics into a biogeographical perspective to understand how environmental variation shapes evolutionary patterns. This approach would also produce more reliable predictions about the effect of environmental change on population persistence and therefore on biodiversity.

High incidence of FXI deficiency in a Spanish town caused by 11 different mutations and the first duplication of F11: Results from the Yecla study.

INTRODUCTION: Factor XI (FXI) deficiency is a rare disorder with molecular heterogeneity in Caucasians but relatively frequent and molecularly homogeneous in certain populations. AIM: To characterize FXI deficiency in a Spanish town of 60 000 inhabitants. METHODS: A total of 324 764 APTT tests were screened during 20 years. FXI was evaluated by FXI:C and by Western blot. Genetic analysis of F11 was performed by sequencing, multiplex ligation-dependent probe amplification and genotyping. RESULTS: Our study identified 46 unrelated cases and 170 relatives with FXI deficiency carrying 12 different genetic defects. p.Cys56Arg, described as founder mutation in the French-Basque population, was identified in 109 subjects from 24 unrelated families. This mutation was also identified in 2% of the general population. p.Cys416Tyr, c.1693G>A and p.Pro538Leu were identified in 7, 6 and 2 unrelated families, respectively. NGS analysis of the whole F11 gene revealed a common haplotype for each of the four recurrent mutations, suggesting a founder effect. The analysis of plasma FXI of four p.Pro538Leu homozygous carriers revealed that this variant was not activated by FXIIa. We identified four mutations previously described in other Caucasian subjects with FXI deficiency (p.Lys536Asn; p.Thr322Ile, p.Arg268Cys and c.325G>A) and four new gene defects: p.(Cys599Tyr) potentially causing a functional deficiency, p.(Ile426Thr), p.(Ile592Thr) and the first worldwide duplication of 1653 bp involving exons 8 and 9. Bleeding was rare and mild. CONCLUSIONS: Our population-cohort study supplies new evidences that FXI deficiency in Caucasians is more common than previously thought and confirmed the wide underlying genetic heterogeneity, caused by both recurrent and sporadic mutations.

Early constraints in sexual dimorphism: survival benefits of feminized phenotypes.

Sexual dimorphism (SD) has evolved in response to selection pressures that differ between sexes. Since such pressures change across an individual's life, SD may vary within age classes. Yet, little is known about how selection on early phenotypes may drive the final SD observed in adults. In many dimorphic species, juveniles resemble adult females rather than adult males, meaning that out of the selective pressures established by sexual selection feminized phenotypes may be adaptive. If true, fitness benefits of early female-like phenotypes may constrain the expression of male phenotypes in adulthood. Using the common kestrel Falco tinnunculus as a study model, we evaluated the fitness advantages of expressing more feminized phenotypes at youth. Although more similar to adult females than to adult males, common kestrel fledglings are still sexually dimorphic in size and coloration. Integrating morphological and chromatic variables, we analysed the phenotypic divergence between sexes as a measure of how much each individual looks like the sex to which it belongs (phenotypic sexual resemblance, PSR). We then tested the fitness benefits associated with PSR by means of the probability of recruitment in the population. We found a significant interaction between PSR and sex, showing that in both sexes more feminized phenotypes recruited more into the population than less feminized phenotypes. Moreover, males showed lower PSR than females and a higher proportion of incorrect sex classifications. These findings suggest that the mechanisms in males devoted to resembling female phenotypes in youth, due to a trend to increase fitness through more feminized phenotypes, may provide a mechanism to constrain the SD in adulthood.

Prevalence of premature ovarian failure in patients with systemic lupus erythematosus.

OBJECTIVE: To estimate the prevalence of premature ovarian failure (POF) and its associated factors in patients with systemic lupus erythematosus (SLE). METHODS: Cross-sectional study including consecutive SLE women <60 years of age attending a rheumatology clinic. A face-to-face interview was undertaken to obtain demographic, gynaecological and lupus characteristics. Additional rheumatologic and endocrine data were retrieved from patients' medical records. POF prevalence was estimated in the study sample and in a subgroup of patients aged <40 years at interview. Associations between POF and selected variables were assessed by logistic regression analyses. RESULTS: A total of 961 patients were analysed. Prevalence of POF, secondary amenorrhea of known cause, menopause and hysterectomy were 5.4%, 0.8%, 7.8% and 4.4%, respectively. In 674 (70%) patients who had not been exposed to cyclophosphamide (CYC) the prevalence of POF was 0.6%. Disease activity over time (OR 1.4 (CI 95% 1.0-1.8, p < 0.05)) and CYC treatment (OR 5.9 (CI 95% 1.8-18.8, p < 0.01)) were associated with higher prevalence. Association between POF and endocrine autoimmune diseases was not found. CONCLUSIONS: In the absence of CYC treatment, the prevalence of POF in lupus patients is consistent with that reported in the general population. The existence of autoimmune processes at the ovary seems unlikely in most lupus patients.

Temporal phase-unwrapping of static surfaces with 2-sensitivity fringe-patterns.

Here we describe a 2-step temporal phase unwrapping formula that uses 2-sensitivity demodulated phases for measuring static surfaces. The first phase demodulation has at most 1-wavelength sensitivity and the second one is G-times (G>>1.0) more sensitive. Measuring static surfaces with 2-sensitivity fringe patterns is well known and recent published methods combine 2-sensitivities measurements mostly by triangulation. Two important applications for our 2-step unwrapping algorithm is profilometry and synthetic aperture radar (SAR) interferometry. In these two applications the object or surface being analyzed is static and highly discontinuous; so temporal unwrapping is the best strategy to follow. Phase-demodulation in profilometry and SAR interferometry is very similar because both share similar mathematical models.

Genetic basis and fitness correlates of dynamic carotenoid-based ornamental coloration in male and female common kestrels Falco tinnunculus.

Knowledge of the genetic basis of sexual ornaments is essential to understand their evolution through sexual selection. Although carotenoid-based ornaments have been instrumental in the study of sexual selection, given the inability of animals to synthesize carotenoids de novo, they are generally assumed to be influenced solely by environmental variation. However, very few studies have directly estimated the role of genes and the environment in shaping variation in carotenoid-based traits. Using long-term individual-based data, we here explore the evolutionary potential of a dynamic, carotenoid-based ornament (namely skin coloration), in male and female common kestrels. We first estimate the amount of genetic variation underlying variation in hue, chroma and brightness. After correcting for sex differences, the chroma of the orange-yellow eye ring coloration was significantly heritable (h2±SE=0.40±0.17), whereas neither hue (h2=0) nor brightness (h2=0.02) was heritable. Second, we estimate the strength and shape of selection acting upon chromatic (hue and chroma) and achromatic (brightness) variation and show positive and negative directional selection on female but not male chroma and hue, respectively, whereas brightness was unrelated to fitness in both sexes. This suggests that different components of carotenoid-based signals traits may show different evolutionary dynamics. Overall, we show that carotenoid-based coloration is a complex and multifaceted trait. If we are to gain a better understanding of the processes responsible for the generation and maintenance of variation in carotenoid-based coloration, these complexities need to be taken into account.

Experimentally elevated levels of testosterone at independence reduce fitness in a territorial bird.

Environmental conditions and individual strategies in early life may have a profound effect on fitness. A critical moment in the life of an organism occurs when an individual reaches independence and stops receiving benefits from its relatives. Understanding the consequences of individual strategies at the time of independence requires quantification of their fitness effects. We explored this period in the Red Grouse (Lagopus lagopus scoticus). In this system, testosterone and parasite (Trichostrongylus tenuis) levels are known to influence survival and reproduction, the two key components of individual fitness. We experimentally and simultaneously manipulated testosterone and parasites at three levels (high, intermediate, and control levels for both factors) in 195 young males in five populations using a factorial experimental design. We explored the effects of our treatments on fitness by monitoring reproduction and survival throughout the life of all males and estimating lambda(ind), a rate-sensitive index of fitness. Parasite challenges increased the number of worms with a time lag, as previously found. However, we did not find significant effects of parasite manipulations on fitness, possibly because parasite abundance did not increase to harmful levels. Our hormone manipulation was successful at increasing testosterone at three different levels. Such increases in hormone levels decreased overall fitness. This was caused by reduced offspring production in the first breeding attempt rather than by any effect of the treatment on bird survival. Our results highlight that investing in high testosterone levels at independence, a strategy that might enhance short-term recruitment probability in territorial species such as Red Grouse, has a fitness cost, and can influence the resolution of the trade-off between reproduction and survival later in life.

High-resolution low-noise 360-degree digital solid reconstruction using phase-stepping profilometry.

In this paper we describe a high-resolution, low-noise phase-shifting algorithm applied to 360 degree digitizing of solids with diffuse light scattering surface. A 360 degree profilometer needs to rotate the object a full revolution to digitize a three-dimensional (3D) solid. Although 360 degree profilometry is not new, we are proposing however a new experimental set-up which permits full phase-bandwidth phase-measuring algorithms. The first advantage of our solid profilometer is: it uses base-band, phase-stepping algorithms providing full data phase-bandwidth. This contrasts with band-pass, spatial-carrier Fourier profilometry which typically uses 1/3 of the fringe data-bandwidth. In addition phase-measuring is generally more accurate than single line-projection, non-coherent, intensity-based line detection algorithms. Second advantage: new fringe-projection set-up which avoids self-occluding fringe-shadows for convex solids. Previous 360 degree fringe-projection profilometers generate self-occluding shadows because of the elevation illumination angles. Third advantage: trivial line-by-line fringe-data assembling based on a single cylindrical coordinate system shared by all 360-degree perspectives. This contrasts with multi-view overlapping fringe-projection systems which use iterative closest point (ICP) algorithms to fusion the 3D-data cloud within a single coordinate system (e.g. Geomagic). Finally we used a 400 steps/rotation turntable, and a 640x480 pixels CCD camera. Higher 3D digitized surface resolutions and less-noisy phase measurements are trivial by increasing the angular-spatial resolution and phase-steps number without any substantial change on our 360 degree profilometer.

Thrombin generation as objective parameter of treatment response in patients with severe haemophilia A and high-titre inhibitors.

In Mexico, 15% of haemophilia A (HA) patients develop inhibitory alloantibodies in response to replacement therapy with factor VIII (FVIII), requiring bypass therapy such as activated prothrombin complex concentrate (APCC). Because bypass therapy has not been broadly available in Mexico even in recent years, this study aimed to evaluate the thrombin generation assay (TGA) in assessing the response to FVIII or APCC treatment in patients with severe HA positive to inhibitors. We studied 189 patients with severe HA. Clinical severity was verified by one-stage APTT-based clotting assay. Inhibitors to FVIII were investigated by the Nijmegen-Bethesda (N-B) method, and type of inhibition was assessed through serial plasma dilutions. Thrombin generation was measured with the calibrated automated thrombogram in inhibitor-positive plasmas previously spiked and incubated with FVIII or APCC. Data were analysed using anova, Student or Fisher's exact tests. We detected 47 (24.9%) subjects with high-titre (5-1700 N-B U mL(-1)) and 25 (13.2%) subjects with low-titre inhibitor antibodies (0.6-4.7 N-B U mL(-1)). We found an association between kinetic behaviour and clinical response to FVIII (P = 0.0049) or vs. FVIII response evaluated with TGA (P = 0.0007). Global concordance between clinical and in vitro response was 70%. By evaluating the capacity of thrombin formation in a plasma sample, TGA predicts the response to FVIII or APCC therapy and allows individual optimization of resources in patients with severe HA and high-titre inhibitors. The inhibition pattern of the antibodies to FVIII:C correlated with the TGA parameters and showed an association with the clinical response to FVIII.

Intra-sexual competition alters the relationship between testosterone and ornament expression in a wild territorial bird.

In a reliable signalling system, individual quality is expected to mediate the costs associated with ornamental displays, with relatively lower costs being paid by individuals of higher quality. These relative costs should depend not only on individual quality, but also on levels of intra-sexual competition. We explored the current and delayed effects that testosterone implants have on bird ornamentation in populations with contrasted population densities, as a proxy for intra-sexual competition. In a replicated experiment, we manipulated testosterone in 196 yearling male red grouse Lagopus lagopus scoticus in autumn in populations of high and low levels of intra-sexual competition. Males were assigned to one of three exogenous testosterone (T) treatments: empty implants (T0), small T implants (T1) or larger T implants (T2). We monitored subsequent changes in testosterone levels, ornament size and carotenoid-based colouration, carotenoid levels and body condition from autumn to spring. Testosterone implants increased testosterone levels, comb redness and comb size, and decreased body condition but these effects depended on levels of intra-sexual competition. Specifically, T2-implanted birds increased testosterone levels and comb size more, and reduced body condition more, in populations where intra-sexual competition was low. In the following spring, testosterone levels of T2-treated birds kept increasing in populations where intra-sexual competition was high but not in populations where intra-sexual competition was low. Our results highlight that levels of intra-sexual competition alter the relationship between testosterone levels and ornament expression, influencing their condition-dependence; they also indicate that the outcome of standard hormone manipulation conducted in free-living animals vary depending on the population context.

Statistical groupings of mental and social health measurements correlate with musculoskeletal capability - A cross sectional study.

OBJECTIVE: A better understanding of the degree to which social health factors contribute uniquely to statistical clusters associated with variation in levels of capability might inform targeted whole person care strategies for more comprehensive management of musculoskeletal health. Therefore, we asked: (1) What are the statistical groupings of social and mental health measurements in patients seeking specialty care for musculoskeletal conditions? (2) Do identified psychosocial groupings correspond with different mean magnitudes of incapability accounting for demographic and clinical factors? METHODS: We included 158 patients seeking musculoskeletal specialty care and collected measures of magnitude of incapability, unhelpful thoughts and distress regarding symptoms, symptoms of depression, symptoms of anxiety, and social health. A k-means clustering algorithm was fit to the data and a linear regression model compared mean PROMIS-PF CAT scores for grouping. RESULTS: A quantitative social health measure contributed to 4 statistical clusters as follows: 1) relatively low levels of all mental health measures and high social health; 2) greater unhelpful thoughts and distress regarding symptoms, average symptoms of general anxiety and depression, and average social health; 3) higher levels of all mental health measures and severely compromised social health; and 4) severely compromised mental health and lower social health. Magnitude of incapability was significantly greater for groups with worse mental and social health. CONCLUSION: The finding of a relatively independent association of social and mental health factors with greater incapability supports the importance of introducing comprehensive health strategies in musculoskeletal specialty care. Strategies may include mindset training and case management of social unmet needs. LEVEL OF EVIDENCE: Level III; Cross-sectional study.

Multivariate heredity of melanin-based coloration, body mass and immunity.

The genetic covariation among different traits may cause the appearance of correlated response to selection on multivariate phenotypes. Genes responsible for the expression of melanin-based color traits are also involved in other important physiological functions such as immunity and metabolism by pleiotropy, suggesting the possibility of multivariate evolution. However, little is known about the relationship between melanin coloration and these functions at the additive genetic level in wild vertebrates. From a multivariate perspective, we simultaneously explored inheritance and selection of melanin coloration, body mass and phytohemagglutinin (PHA)-mediated immune response by using long-term data over an 18-year period collected in a wild population of the common kestrel Falco tinnunculus. Pedigree-based quantitative genetic analyses showed negative genetic covariance between melanin-based coloration and body mass in male adults and positive genetic covariance between body mass and PHA-mediated immune response in fledglings as predicted by pleiotropic effects of melanocortin receptor activity. Multiple selection analyses showed an increased fitness in male adults with intermediate phenotypic values for melanin color and body mass. In male fledglings, there was evidence for a disruptive selection on rump gray color, but a stabilizing selection on PHA-mediated immune response. Our results provide an insight into the evolution of multivariate traits genetically related with melanin-based coloration. The differences in multivariate inheritance and selection between male and female kestrels might have resulted in sexual dimorphism in size and color. When pleiotropic effects are present, coloration can evolve through a complex pathway involving correlated response to selection on multivariate traits.

Synchronous phase-demodulation and harmonic rejection of 9-step pixelated dynamic interferograms.

We propose a novel synchronous phase-demodulation of pixelated interferograms using squared 3x3 phase-shifted unit-cells. This 3x3 unit-cell is tiled over the CCD image sensor to create a two-dimensional (2D) pixelated carrier. Our synchronous phase-demodulation uses this 2D carrier to demodulate the pixelated interferogram as in the standard 2x2 unit-cell case. The main motivation behind the use of a 3x3 pixelated carrier (instead of the usual 2x2) is its higher harmonic robustness, allowing one to demodulate intensity-distorted fringe patterns. The harmonic rejection robustness of our spatial 3x3 configuration equals the robustness of the temporal least-squares 9-step phase-shifting algorithm (PSA). In other words, extending from the usual 2x2 phase-shifting unit-cell to 3x3 unit-cells, one extends the harmonic rejection of the demodulation algorithm. Finally we also prove that our proposed 9-step, 3x3 pixelated carrier uses the 2D available spectral space more efficiently than using these 9-steps in a linear spatial-carrier configuration.

Environmental heterogeneity influences the reliability of secondary sexual traits as condition indicators.

Numerous studies have shown positive associations between ornaments and condition, as predicted by indicator models of sexual selection. However, this idea is continuously challenged by opposite results, which reveal our lack of full understanding of how sexual selection works. Environmental heterogeneity may explain such inconsistencies, but valid field tests of this idea are currently lacking. We first analysed the relationship between condition and ornament expression from nine populations over 7 years in a wild bird, the red grouse Lagopus lagopus scoticus. We then manipulated male aggressiveness at the population level by means of testosterone implants in a replicated field experiment. We found that the relationship between condition and ornamentation varied greatly between environments and became stronger when environmental conditions (ECs) were worse or when aggressiveness in the population was experimentally increased. Some ornaments may therefore reliably advertise a better condition only in adverse ECs. Considering environmental heterogeneity can help reconcile conflicting findings regarding the reliability of ornaments as indicators of condition and will help our understanding of sexual selection processes.

A Fokker-Planck Framework for Parameter Estimation and Sensitivity Analysis in Colon Cancer.

A new stochastic framework for parameter estimation and uncertainty quantification in colon cancer-induced immune response is presented. The dynamics of colon cancer is given by a stochastic process that captures the inherent randomness in the system. The stochastic framework is based on the Fokker-Planck equation that represents the evolution of the probability density function corresponding to the stochastic process. An optimization problem is formulated that takes input individual patient data with randomness present, and is solved to obtain the unknown parameters corresponding to the individual tumor characteristics. Furthermore, sensitivity analysis of the optimal parameter set is performed to determine the parameters that need to be controlled, thus, providing information of the type of drugs that can be used for treatment.

First face composite-tissue transplant recipient successfully treated for cytomegalovirus infection with preemptive valganciclovir treatment.

Little is known about cytomegalovirus (CMV) infection after face transplantation, since only two of the 11 cases of face transplantation reported worldwide have documented a CMV infection after transplantation. Herein, we present the first report of a composite-tissue face allotransplant recipient at high risk for CMV infection (D(+)/R(-) [CMV serpositive donor positive/CMV seronegative receptor]) undergoing preemptive treatment. Preemptive treatment was safe and effective for controlling CMV infection and thus promoting early acquisition of a CMV-specific immune response that protected the patient from late-onset CMV disease.