Organoid cystogenesis reveals a critical role of microenvironment in human polycystic kidney disease.

Polycystic kidney disease (PKD) is a life-threatening disorder, commonly caused by defects in polycystin-1 (PC1) or polycystin-2 (PC2), in which tubular epithelia form fluid-filled cysts. A major barrier to understanding PKD is the absence of human cellular models that accurately and efficiently recapitulate cystogenesis. Previously, we have generated a genetic model of PKD using human pluripotent stem cells and derived kidney organoids. Here we show that systematic substitution of physical components can dramatically increase or decrease cyst formation, unveiling a critical role for microenvironment in PKD. Removal of adherent cues increases cystogenesis 10-fold, producing cysts phenotypically resembling PKD that expand massively to 1-centimetre diameters. Removal of stroma enables outgrowth of PKD cell lines, which exhibit defects in PC1 expression and collagen compaction. Cyclic adenosine monophosphate (cAMP), when added, induces cysts in both PKD organoids and controls. These biomaterials establish a highly efficient model of PKD cystogenesis that directly implicates the microenvironment at the earliest stages of the disease.

Semiochemicals Associated with the Western Flower Thrips Attraction: A Systematic Literature Review and Meta-Analysis.

The study of the semiochemicals of the western flower thrips (WFT), Frankliniella occidentalis, Pergande (Thysanoptera: Thripidae), is a relevant topic that spans the last two decades. Approximately a hundred articles published on this subject from 2000 to 2022 can be found in academic databases, representing approximately 5% of the research on this important pest. These topics have generated a platform for novel research with a high potential for development. However, to move on to a new research step, an effectiveness evaluation of the compounds discovered so far is necessary. This review conducted a systematic analysis of the research focused on the semiochemicals (kairomones, pheromones, and attractants) for this pest. Papers from the past three decades on WFT attraction to semiochemicals were collected from databases using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The number of individuals attracted to compounds was extracted from the papers and compiled for analysis. With this information, an attraction ratio was calculated. Forty-one possible attractants were found in the literature, with methyl isonicotinate being the most-studied compound so far, with the third-highest attraction ratio. δ-Decalactone was the compound with the highest attraction ratio, but it was one of the least studied. A meta-analysis of the WFT choosing proportion was performed for the compounds with more trials found in the literature. The predicted mean choice percentages for methyl isonicotinate (MIN) and Lurem-TR, the MIN's commercial product, were 76.6% and 66.6%, respectively. There was a convergence among the analyzed studies showing a high degree of research focus on the same group of nitrogen-containing compounds (mainly the pyridine structure). These findings call for future research to diversify the discovery and evaluation of attractive compounds in this relevant study area.

Phylogenomics reveals a diverse Rickettsiales type IV secretion system.

With an obligate intracellular lifestyle, Alphaproteobacteria of the order Rickettsiales have inextricably coevolved with their various eukaryotic hosts, resulting in small, reductive genomes and strict dependency on host resources. Unsurprisingly, large portions of Rickettsiales genomes encode proteins involved in transport and secretion. One particular transporter that has garnered recent attention from researchers is the type IV secretion system (T4SS). Homologous to the well-studied archetypal vir T4SS of Agrobacterium tumefaciens, the Rickettsiales vir homolog (rvh) T4SS is characterized primarily by duplication of several of its genes and scattered genomic distribution of all components in several conserved islets. Phylogeny estimation suggests a single event of ancestral acquirement of the rvh T4SS, likely from a nonalphaproteobacterial origin. Bioinformatics analysis of over 30 Rickettsiales genome sequences illustrates a conserved core rvh scaffold (lacking only a virB5 homolog), with lineage-specific diversification of several components (rvhB1, rvhB2, and rvhB9b), likely a result of modifications to cell envelope structure. This coevolution of the rvh T4SS and cell envelope morphology is probably driven by adaptations to various host cells, identifying the transporter as an important target for vaccine development. Despite the genetic intractability of Rickettsiales, recent advancements have been made in the characterization of several components of the rvh T4SS, as well as its putative regulators and substrates. While current data favor a role in effector translocation, functions in DNA uptake and release and/or conjugation cannot at present be ruled out, especially considering that a mechanism for plasmid transfer in Rickettsia spp. has yet to be proposed.

[Aortic valve calcification prevalence and association with coronary risk factors and atherosclerosis in Mexican population]. / Prevalencia y asociación de la calcificación valvular aórtica con factores de riesgo y aterosclerosis coronaria en población mexicana.

OBJETIVE: The prevalence of aortic valve calcification (AVC), strongly influenced by ethnicity, is unknown in Mexican population. The aim of this study was to investigate the prevalence of AVC and its associations with cardiovascular risk factors and coronary artery calcification (CAC), in Mexican subjects. METHODS: In 1,267 subjects (53% women) without known coronary heart disease, aged 35 to 75 years, AVC and CAC were assessed by multidetector-computed tomography using the Agatston score. Cardiovascular risk factors were documented in all participants. The associations of AVC with CAC and risk factors were assessed by multivariable logistic regression analyses. RESULTS: The overall prevalence of AVC and CAC was 19.89% and 26.5%, respectively. AVC and CAC increased with age and were found more frequently in men (25.5% and 37.1%, respectively) than in women (14.9% and 13.0%, respectively). AVC was observed in only 8.5% of subjects without CAC, while those with CAC 1-99, 100-399, and >400 Agatston units had AVC prevalences of 36.8%, 56.8%, and 84.0%, respectively. The multivariable logistic regression analyses, adjusted for age, gender, obesity, physical inactivity, hypertension, dyslipidemia and high insulin levels, showed that the presence of CAC (OR [CI95%]: 3.23 [2.26-4.60]), obesity (1.94 [1.35-2.79]), male gender (1.44 [1.01-2.05]) and age (1.08 [1.03-1.10]), were significant independent predictors of AVC. CONCLUSION: Prevalence of AVC is high and significantly associated with atherosclerotic risk factors and CAC in this Mexican population.

[Prevalence and extent of coronary artery calcification in an asymptomatic cardiovascular Mexican population: Genetics of Atherosclerotic Disease study]. / Prevalencia y extensión de la calcificación arterial coronaria en población mexicana asintomática cardiovascular: estudio Genética de la Enfermedad Aterosclerosa.

OBJECTIVE: The prevalence of coronary artery calcification (CAC), a specific marker of atherosclerosis, is unknown in Mexico. Our aim was to investigate the prevalence and quantity of CAC and their association with cardiovascular risk factors in a Mexican population. METHODS: CAC was measured by multidetector computed tomography in asymptomatic subjects who participated in the Genetics of Atherosclerotic Disease study. Cardiovascular risk factors and medication were recorded. RESULTS: The sample included 1,423 individuals (49.5% men), aged 53.7±8.4 years. Those with CAC showed a higher prevalence of dyslipidaemia, diabetes, hypertension, and other risk factors. The prevalence of CAC>0 Agatston units was significantly higher among men (40%) than among women (13%). Mean values of CAC score increased consistently with increasing age and were higher in men than women in each age group. Age and high low density lipoprotein cholesterol were independently associated with prevalence of CAC>0 in men and women, while increasing systolic blood pressure in women and age in both genders showed an independent association with CAC extension. CONCLUSIONS: In the Mexican population the prevalence and extent of CAC were much higher in men than in women, and strongly increased with age. Independent predictors of CAC prevalence were age and low density lipoprotein cholesterol (LDL-C).

[Secondary embryonary root associated with seed germination in Garcinia intermedia (Clusiaceae) and its possible role in seedling survival]. / Raíz secundaria embrional asociada a la germinación de Garcinia intermedia (Clusiaceae) y su posible papel en la supervivencia de las plántulas.

Germination tests on Garcinia intermedia (Clusiaceae) seeds showed the growth of two types of roots: additionally to the primary root, a secondary root crosses the seed lengthwise. To determine its possible role on the survival and growth of this species, 90 seedlings at least six months old (collected in Central Costa Rica) were planted in plastic bags with organic soil, and placed in a greenhouse. The seedlings were treated as follows: treatments in which the primary or secondary root was cut off, and a control group with both roots intact (30 replicates each). After three months 10 seedlings/month/treatment were extracted to measure their height, basal diameter, root length (main and secondary root), and biomass of the stem, roots and seed (without its coat). Control seedlings had the highest growth, followed by those without secondary roots. Nonetheless, more than 90% of the seedlings whose primary roots were cut off, survived after five months of the excision treatment, in part due to the capacity of this species to regenerate its radical system through the seed reserves, sprouting of a primary-like root, and/or the growth stimulus of the secondary root (60% of the total: 20% with sprouts from the primary root stump, 13.3% with a growth stimulus of the secondary root, and 26.7% with both conditions). The length of the sprouted roots was significantly different only on those plants that were extracted during the first two monthly measurements, when compared with the control (F6 = 18.6, F7 = 16.0, p < 0.01).

Insulin Resistance in Adipose Tissue but Not in Liver Is Associated with Aortic Valve Calcification.

Background. Insulin resistance is involved in the pathogenesis of cardiovascular disease, but its relationship with cardiovascular calcification has yielded conflicting results. The purpose of the present study was to investigate the role of hepatic and adipose tissue insulin resistance on the presence of coronary artery (CAC > 0) and aortic valve calcification (AVC > 0). Methods. In 1201 subjects (52% women, 53.6 ± 9.3 years old) without familiar and personal history of coronary heart disease, CAC and AVC were assessed by multidetector-computed tomography. Cardiovascular risk factors were documented and lipid profile, inflammation markers, glucose, insulin, and free fatty acids were measured. Hepatic insulin resistance (HOMA-IR) and adipose tissue insulin resistance (Adipo-IR) indices were calculated. Results. There was a significant relationship between HOMA-IR and Adipo-IR indices (r = 0.758, p < 0.001). Participants in the highest quartiles of HOMA-IR and Adipo-IR indices had a more adverse cardiovascular profile and higher prevalence of CAC > 0 and AVC > 0. After full adjustment, subjects in the highest quartile of Adipo-IR index had higher odds of AVC > 0 (OR: 2.40; 95% CI: 1.30-4.43), as compared to those in the lowest quartile. Conclusions. Adipo-IR was independently associated with AVC > 0. This suggests that abnormal adipose tissue function favors insulin resistance that may promote the development and progression of AVC.

How far is that by air? The derivation of an air: ground coefficient.

The objective of this study was to derive a simple equation to convert distances between air miles traveled by a helicopter and ground miles traveled by an ambulance. We performed a retrospective analysis of a convenience sampling of 245 "lights and sirens" ground ambulance transports between 1993 and 1997. Ground distances were recorded from odometer miles for each transport. Air miles were calculated using the Global Positioning System (GPS), measuring the distance in a straight line from the scene to the hospital. Air and ground distances were entered into a computerized spreadsheet, and the correlation coefficient and regression equation were derived. A simple approximation equation was developed and compared against the derived regression equation. There was a strong linear correlation between ground miles and air miles at virtually all distances studied (R = 0.932, R(2) = 0.869). Regression analysis revealed the following relationship: Ground miles = 0.94 + 1.25 (air miles). This was simplified to an approximation of: Ground miles = 1.3 (air miles). The approximation equation yielded an answer within 1 mile of the regression equation for distances up to 40 air miles. It is concluded that in a mixed rural and urban EMS system, one may convert air and ground mileage estimates by using the simple relationship: Ground miles = 1.3 (air miles). This conversion coefficient may prove useful for EMS personnel in designing reasonable helicopter utilization policies, making accurate transport decisions and conducting research.

Prevalencia y extensión de la calcificación arterial coronaria en población mexicana asintomática cardiovascular: estudio Genética de la Enfermedad Aterosclerosa / Prevalence and extent of coronary artery calcification in an asymptomatic cardiovascular Mexican population: Genetics of Atherosclerotic Disease study

Resumen: Objetivo: La prevalencia de calcificación arterial coronaria (CAC), marcador específico de aterosclerosis, no es conocida en México. Nuestro objetivo fue investigar la prevalencia y extensión de CAC y su asociación con factores de riesgo cardiovascular en población mexicana. Métodos: La CAC fue medida por tomografía computarizada multidetector en individuos asintomáticos que participaron en el estudio Genética de la Enfermedad Aterosclerosa. Los factores de riesgo cardiovascular y los medicamentos fueron registrados. Resultados: La muestra incluyó 1,423 individuos (49.5% hombres), con una edad de 53.7 ± 8.4 años. Los portadores de CAC mostraron prevalencias más altas de dislipidemia, diabetes, hipertensión y otros factores de riesgo. La prevalencia de CAC > 0 unidades Agatston fue de 27%, significativamente más alta en hombres (40%) que en mujeres (13%). Los valores medios del puntaje de CAC aumentaron consistentemente con la edad y fueron más altos en hombres que en mujeres en todos los grupos etarios. La edad y el c-LDL elevado se asociaron de manera independiente con la prevalencia de CAC > 0 en hombres y mujeres, mientras que la presión arterial sistólica en las mujeres, y el incremento de la edad en ambos géneros mostró una asociación independiente con la severidad de CAC. Conclusiones: En población mexicana la prevalencia y la extensión de CAC fueron mucho más altas en hombres que en mujeres y aumentaron consistentemente con la edad. Los predictores independientes de la prevalencia de CAC fueron la edad y el c-LDL.

Abstract: Objective: The prevalence of coronary artery calcification (CAC), a specific marker of atherosclerosis, is unknown in Mexico. Our aim was to investigate the prevalence and quantity of CAC and their association with cardiovascular risk factors in a Mexican population. Methods: CAC was measured by multidetector computed tomography in asymptomatic subjects who participated in the Genetics of Atherosclerotic Disease study. Cardiovascular risk factors and medication were recorded. Results: The sample included 1,423 individuals (49.5% men), aged 53.7 ± 8.4 years. Those with CAC showed a higher prevalence of dyslipidaemia, diabetes, hypertension, and other risk factors. The prevalence of CAC > 0 Agatston units was significantly higher among men (40%) than among women (13%). Mean values of CAC score increased consistently with increasing age and were higher in men than women in each age group. Age and high low density lipoprotein cholesterol were independently associated with prevalence of CAC > 0 in men and women, while increasing systolic blood pressure in women and age in both genders showed an independent association with CAC extension. Conclusions: In the Mexican population the prevalence and extent of CAC were much higher in men than in women, and strongly increased with age. Independent predictors of CAC prevalence were age and low density lipoprotein cholesterol (LDL-C).

Prevalencia y asociación de la calcificación valvular aórtica con factores de riesgo y aterosclerosis coronaria en población mexicana / Aortic valve calcification prevalence and association with coronary risk factors and atherosclerosis in Mexican population

Resumen: Objetivo: La prevalencia de calcificación valvular aórtica (CVA) tiene influencia importante de la etnia y se desconoce en población mexicana. Nuestro objetivo fue investigar la prevalencia de CVA y sus asociaciones con factores de riesgo cardiovascular y calcificación arterial coronaria (CAC). Método: En 1,267 sujetos (53% mujeres) sin enfermedad coronaria conocida y con edad de 35 a 75 años, la CVA y la CAC se evaluaron mediante tomografía computada multidetector, utilizando el método de Agatston. Los factores de riesgo cardiovascular se documentaron en todos los participantes. Las asociaciones de CVA con CAC y factores de riesgo se estimaron usando el análisis de regresión logística múltiple. Resultados: La prevalencia global de CVA y CAC fue del 19.89% y del 26.5%, respectivamente. Ambas condiciones aumentaron con la edad y se encontraron con mayor frecuencia en hombres (25.5 y 37.1%, respectivamente) que en mujeres (14.9 y 13%, respectivamente). La CVA se observó en únicamente el 8.5% de los sujetos sin CAC, mientras que en aquellos con CAC 1-99, 100-399 y > 400 unidades Agatston, las prevalencias fueron del 36.8, 56.8 y 84%, respectivamente. El análisis de regresión logística múltiple ajustado por edad, género, obesidad, inactividad física, hipertensión, dislipidemia y valores altos de insulina, mostró que la presencia de CAC (RM [IC95%]: 3.23 [2.26-4.60]), obesidad (1.94 [1.35-2.79]), género masculino (1.44 [1.01-2.05]) y edad (1.08 [1.03-1.10]), fueron predictores independientes y significativos de la CVA. Conclusiones: La prevalencia de CVA es alta y se asocia significativamente con factores de riesgo aterosclerótico y CAC en población mexicana.

Abstract: Objetive: The prevalence of aortic valve calcification (AVC), strongly influenced by ethnicity, is unknown in Mexican population. The aim of this study was to investigate the prevalence of AVC and its associations with cardiovascular risk factors and coronary artery calcification (CAC), in Mexican subjects. Methods: In 1,267 subjects (53% women) without known coronary heart disease, aged 35 to 75 years, AVC and CAC were assessed by multidetector-computed tomography using the Agatston score. Cardiovascular risk factors were documented in all participants. The associations of AVC with CAC and risk factors were assessed by multivariable logistic regression analyses. Results: The overall prevalence of AVC and CAC was 19.89% and 26.5%, respectively. AVC and CAC increased with age and were found more frequently in men (25.5% and 37.1%, respectively) than in women (14.9% and 13.0%, respectively). AVC was observed in only 8.5% of subjects wit-hout CAC, while those with CAC 1-99, 100-399, and > 400 Agatston units had AVC prevalences of 36.8%, 56.8%, and 84.0%, respectively. The multivariable logistic regression analyses, adjusted for age, gender, obesity, physical inactivity, hypertension, dyslipidemia and high insulin levels, showed that the presence of CAC (OR [CI95%]: 3.23 [2.26-4.60]), obesity (1.94 [1.35-2.79]), male gender (1.44 [1.01-2.05]) and age (1.08 [1.03-1.10]), were significant independent predictors of AVC. Conclusion: Prevalence of AVC is high and significantly associated with atherosclerotic risk factors and CAC in this Mexican population.

Involvement of TLR2 and TLR4 in cell responses to Rickettsia akari.

A better understanding of the pathogenesis of rickettsial disease requires elucidation of mechanisms governing host defense during infection. TLRs are primary sensors of microbial pathogens that activate innate immune cells, as well as initiate and orchestrate adaptive immune responses. However, the role of TLRs in rickettsia recognition and cell activation remains poorly understood. In this study, we examined the involvement of TLR2 and TLR4 in recognition of Rickettsia akari, a causative agent of rickettsialpox. Transfection-based complementation of TLR2/4-negative HEK293T cells with human TLR2 or TLR4 coexpressed with CD14 and MD-2 enabled IκB-α degradation, NF-κB reporter activation, and IL-8 expression in response to heat-killed (HK) R. akari. The presence of the R753Q TLR2 or D299G TLR4 polymorphisms significantly impaired the capacities of the respective TLRs to signal HK R. akari-mediated NF-κB reporter activation in HEK293T transfectants. Blocking Ab against TLR2 or TLR4 markedly inhibited TNF-α release from human monocytes stimulated with HK R. akari, and TNF-α secretion elicited by infection with live R. akari was reduced significantly only upon blocking of TLR2 and TLR4. Live and HK R. akari exerted phosphorylation of IRAK1 and p38 MAPK in 293/TLR4/MD-2 or 293/TLR2 stable cell lines, whereas only live bacteria elicited responses in TLR2/4-negative HEK293T cells. These data demonstrate that HK R. akari triggers cell activation via TLR2 or TLR4 and suggest use of additional TLRs and/or NLRs by live R. akari.

Endotoxin tolerance dysregulates MyD88- and Toll/IL-1R domain-containing adapter inducing IFN-beta-dependent pathways and increases expression of negative regulators of TLR signaling.

Endotoxin tolerance reprograms cell responses to LPS by repressing expression of proinflammatory cytokines, while not inhibiting production of anti-inflammatory cytokines and antimicrobial effectors. Molecular mechanisms of induction and maintenance of endotoxin tolerance are incompletely understood, particularly with regard to the impact of endotoxin tolerization on signalosome assembly, activation of adaptor-kinase modules, and expression of negative regulators of TLR signaling in human cells. In this study, we examined LPS-mediated activation of MyD88-dependent and Toll-IL-1R-containing adaptor inducing IFN-beta (TRIF)-dependent pathways emanating from TLR4 and expression of negative regulators of TLR signaling in control and endotoxin-tolerant human monocytes. Endotoxin tolerization suppressed LPS-inducible TLR4-TRIF and TRIF-TANK binding kinase (TBK)1 associations, induction of TBK1 kinase activity, activation of IFN regulatory factor (IRF)-3, and expression of RANTES and IFN-beta. Tolerance-mediated dysregulation of the TLR4-TRIF-TBK1 signaling module was accompanied by increased levels of suppressor of IkappaB kinase-epsilon (SIKE) and sterile alpha and Armadillo motif-containing molecule (SARM). LPS-tolerant cells showed increased expression of negative regulators Toll-interacting protein (Tollip), suppressor of cytokine signaling (SOCS)-1, IL-1R-associated kinase-M, and SHIP-1, which correlated with reduced p38 phosphorylation, IkappaB-alpha degradation, and inhibited expression of TNF-alpha, IL-6, and IL-8. To examine functional consequences of increased expression of Tollip in LPS-tolerized cells, we overexpressed Tollip in 293/TLR4/MD-2 transfectants and observed blunted LPS-inducible activation of NF-kappaB and RANTES, while TNF-alpha responses were not affected. These data demonstrate dysregulation of TLR4-triggered MyD88- and TRIF-dependent signaling pathways and increased expression of negative regulators of TLR signaling in endotoxin-tolerant human monocytes.

When is the helicopter faster? A comparison of helicopter and ground ambulance transport times.

BACKGROUND: A retrospective analysis of 7,854 ground ambulance and 1,075 helicopter transports was conducted. METHODS: The 911-hospital arrival intervals for three transport methods were compared: ground, helicopter dispatched simultaneously with ground unit, and helicopter dispatched nonsimultaneously after ground unit response. RESULTS: Compared with ground transports, simultaneously dispatched helicopter transports had significantly shorter 911-hospital arrival intervals at all distances greater than 10 miles from the hospital. Nonsimultaneously dispatched helicopter transport was significantly faster than ground at distances greater than 45 miles, and simultaneous helicopter dispatch was faster than nonsimultaneous at virtually all distances. Ground transport was significantly faster than either air transport modality at distances less than 10 miles from the hospital. CONCLUSION: Ground ambulance transport provided the shortest 911-hospital arrival interval at distances less than 10 miles from the hospital. At distances greater than 10 miles, simultaneously dispatched air transport was faster. Nonsimultaneous dispatched helicopter transport was faster than ground if greater than 45 miles from the hospital.

Mortalidad por suicidio en la provincia de Pinar del Río

Se trata de una investigación descriptiva y retrospectiva sobre el comportamiento de la mortalidad por suicidio en la provincia Pinar del Río durante el año 2001, de acuerdo con una serie de variables seleccionadas. Se estudiaron todos los fallecidos por esa causa en el período señalado, que fueron un total de 110 para una tasa de 14,9 por 100 000 habitantes, por lo que es la séptima causa de muerte en la provincia. Llama la atención el amplio predominio del sexo masculino, de la incidencia en la tercera edad, y el hecho de no haber tenido este año el municipio Sandino fallecido alguno por esta causa, así como que el municipio de mayor número de fallecidos por este motivo fue Viñales con una tasa de 26,0 por 100 000 habitantes.

A retrospective descriptive research work on the situation of mortality from suicide in Pinar del Río province during 2001 was carried out based on a group of selected variables. All the deaths form this cause, which amounted to 110 persons for a rate of 14.9 per 100 000 pop, were studied. Suicide was the seventh cause of death in the province. It should be underlined that males prevailed, the incidence of the elderly was high and that Sandino municipality had no death from suicide in this year whereas Viñales municipality showed the highest number of deceased, with a mortality rate of 26 per 100 000 pop.