Perinatal outcomes following abdominoplasty: a retrospective study and review of current literature.

BACKGROUND: Abdominoplasty surgery is a common body contouring surgery to remove excess fat and skin and restore weakened or separated abdominal muscles caused by aging, pregnancy, or weight fluctuations. There is limited literature regarding patient and pregnancy outcomes after abdominoplasty. OBJECTIVE: This study aimed to determine whether there was a correlation between adverse pregnancy outcomes and history of abdominoplasty. STUDY DESIGN: Our study used a large federated deidentified national health research network with data sourced from 68 healthcare organizations within the United States (TriNetX; data accessed on August 19, 2022). All patients with a record of pregnancy were identified using the International Classification of Diseases, Ninth Revision and Tenth Revision, codes and were grouped into those with a history of abdominoplasty and those without. This study evaluated the perinatal outcomes of fetal growth restriction, abnormal umbilical artery Dopplers, gestational hypertension, preeclampsia, preterm delivery, preterm premature rupture of membranes, gestational diabetes mellitus, macrosomia, stillbirth, abnormal placentation, and wound disruption or infection occurring during a patient's pregnancy after abdominoplasty. Propensity matching was performed to account for potential confounders. An alpha level of <.05 was considered statistically significant. RESULTS: Of the 44,737 patients meeting our criteria, 304 had a history of abdominoplasty, whereas 44,433 did not (control). Our study found that patients with a history of abdominoplasty had significantly higher gravidity, were largely located in the Southern and Midwest region, and had higher counts of vaginal deliveries and cesarean deliveries than the control cohort (Table 1). After propensity score matching, our study found a lower risk of preeclampsia and preterm premature rupture of membranes in patients with abdominoplasty (odds ratio, 0.46; 95% confidence interval, 0.32-0.67; P<.0001) (Table 2). Furthermore, abdominoplasty was associated with an increased risk of preterm delivery (odds ratio, 2.15; 95% confidence interval, 1.48-3.13; P=.0002) (Table 2). Lastly, this study did not find significant differences in the other perinatal outcomes (Table 2). CONCLUSION: Our data suggest that abdominoplasty may be associated with a relative increase in the rates of preterm delivery and cesarean delivery and that other perinatal outcomes are not increased. This provides evidence that future desire for pregnancy need not be a relative contraindication to abdominoplasty.

Bell's Palsy and COVID-19: Insights from a Population-Based Analysis.

Background: Coronavirus disease 2019 (COVID-19) has been linked to Bell's palsy and facial paralysis. Studies have also shown increased risk of Bell's palsy in unvaccinated COVID-19 patients. Objective: To compare the relationship between Bell's palsy and COVID-19 infection and vaccination. Design: This is a retrospective longitudinal study. Methods: The COVID-19 research network was used to identify patients with facial palsy presenting to 70 health care organizations in the United States. The incidence of Bell's palsy was measured within an 8-week window after COVID-19 test or vaccination event in identified patients. Results: Incidence of facial palsy diagnosis (0.99%) was higher than the background rate within 2 months of COVID-19 infection. When compared with their negative counterparts, patients with COVID-19 infection had significantly higher risk of Bell's palsy (risk ratio [RR] = 1.77, p < 0.01) and facial weakness (RR = 2.28, p < 0.01). Risk ratio was also amplified when evaluating Bell's palsy (RR = 12.57, p < 0.01) and facial palsy (RR = 44.43; p < 0.01) in COVID-19-infected patients against patients who received COVID-19 vaccination. Conclusion: In our patient population, there is a higher risk of developing facial palsy within 2 months of COVID-19 infection versus vaccination. Vaccinated patients are not at higher risk of developing facial palsy.

Prevalence and Predictors of Barrett's Esophagus After Negative Initial Endoscopy: Analysis From Two National Databases.

BACKGROUND & AIMS: Guidelines suggest a single screening esophagogastroduodenoscopy (EGD) in patients with multiple risk factors for Barrett's esophagus (BE). We aimed to determine BE prevalence and predictors on repeat EGD after a negative initial EGD, using 2 large national databases (GI Quality Improvement Consortium [GIQuIC] and TriNetX). METHODS: Patients who underwent at least 2 EGDs were included and those with BE or esophageal adenocarcinoma detected at initial EGD were excluded. Patient demographics and prevalence of BE on repeat EGD were collected. Multivariate logistic regression was performed to assess for independent risk factors for BE detected on the repeat EGD. RESULTS: In 214,318 and 153,445 patients undergoing at least 2 EGDs over a median follow-up of 28-35 months, the prevalence of BE on repeat EGD was 1.7% in GIQuIC and 3.4% in TriNetX, respectively (26%-45% of baseline BE prevalence). Most (89%) patients had nondysplastic BE. The prevalence of BE remained stable over time (from 1 to >5 years from negative initial EGD) but increased with increasing number of risk factors. BE prevalence in a high-risk population (gastroesophageal reflux disease plus ≥1 risk factor for BE) was 3%-4%. CONCLUSIONS: In this study of >350,000 patients, rates of BE on repeat EGD ranged from 1.7%-3.4%, and were higher in those with multiple risk factors. Most were likely missed at initial evaluation, underscoring the importance of a high-quality initial endoscopic examination. Although routine repeat endoscopic BE screening after a negative initial examination is not recommended, repeat screening may be considered in carefully selected patients with gastroesophageal reflux disease and ≥2 risk factors for BE, potentially using nonendoscopic tools.

Frequency of Parkinson disease following COVID-19 infection: A two-year retrospective cohort study.

INTRODUCTION: COVID-19 infection is known to cause various neurological symptoms, and potentially increases the risk of developing subsequent neurodegenerative conditions including parkinsonism. To our knowledge, no study to date has used a large data set in the United States to ascertain the risk of developing incident Parkinson disease in patients with history of COVID-19 infection compared to the risk amongst those without prior COVID-19 infection. METHODS: We utilized data from TriNetX electronic health records network which includes 73 healthcare organizations and over 107 million patients. We compared adult patients with and without COVID-19 infection, with health records from January 1, 2020 through July 26, 2022, to determine the relative risk of developing Parkinson disease stratified by 3-month intervals. We used propensity score matching to control for patients' age, sex, and smoking history. RESULTS: We collected data on 27,614,510 patients meeting our study criteria: 2,036,930 patients with a positive COVID-19 infection (COVID-19) and 25,577,580 without a positive COVID-19 infection (non-COVID-19). After propensity score matching, age, sex, and smoking history differences became non-significant, with 2,036,930 patients in each cohort. After propensity score matching, we found significantly increased odds of new onset Parkinson disease in the COVID-19 cohort at three, six, nine, and twelve months from the index event, with peak odds ratio at six months. After twelve months there is no significant difference between the COVID-19 group and non-COVID-19 group. CONCLUSIONS: There may be a transiently increased risk of developing Parkinson disease in the first year following COVID-19 infection.

Association between chiropractic spinal manipulation and lumbar discectomy in adults with lumbar disc herniation and radiculopathy: retrospective cohort study using United States' data.

OBJECTIVES: Chiropractic spinal manipulative therapy (CSMT) and lumbar discectomy are both used for lumbar disc herniation (LDH) and lumbosacral radiculopathy (LSR); however, limited research has examined the relationship between these therapies. We hypothesised that adults receiving CSMT for newly diagnosed LDH or LSR would have reduced odds of lumbar discectomy over 1-year and 2-year follow-up compared with those receiving other care. DESIGN: Retrospective cohort study. SETTING: 101 million patient US health records network (TriNetX), queried on 24 October 2022, yielding data from 2012 query. PARTICIPANTS: Adults age 18-49 with newly diagnosed LDH/LSR (first date of diagnosis) were included. Exclusions were prior lumbar surgery, absolute indications for surgery, trauma, spondylolisthesis and scoliosis. Propensity score matching controlled for variables associated with the likelihood of discectomy (eg, demographics, medications). INTERVENTIONS: Patients were divided into cohorts according to receipt of CSMT. PRIMARY AND SECONDARY OUTCOME MEASURES: ORs for lumbar discectomy; calculated by dividing odds in the CSMT cohort by odds in the cohort receiving other care. RESULTS: After matching, there were 5785 patients per cohort (mean age 36.9±8.2). The ORs (95% CI) for discectomy were significantly reduced in the CSMT cohort compared with the cohort receiving other care over 1-year (0.69 (0.52 to 0.90), p=0.006) and 2-year follow-up (0.77 (0.60 to 0.99), p=0.040). E-value sensitivity analysis estimated the strength in terms of risk ratio an unmeasured confounding variable would need to account for study results, yielding point estimates for each follow-up (1 year: 2.26; 2 years: 1.92), which no variables in the literature reached. CONCLUSIONS: Our findings suggest receiving CSMT compared with other care for newly diagnosed LDH/LSR is associated with significantly reduced odds of discectomy over 2-year follow-up. Given socioeconomic variables were unavailable and an observational design precludes inferring causality, the efficacy of CSMT for LDH/LSR should be examined via randomised controlled trial to eliminate residual confounding.

Accuracy of Ultrasound Elastography and Fibrosis-4 Index (FIB-4) in Ruling Out Cirrhosis in Obese Non-Alcoholic Fatty Liver Disease (NAFLD) Patients.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of advanced liver disease in the USA. Liver biopsy, the gold standard diagnostic test for evaluating liver fibrosis, is associated with significant risk and expense. The accuracy of ultrasound elastography and Fibrosis-4 index (FIB-4) in the obese NAFLD population is unknown. We aimed to compare the accuracy of ultrasound elastography and FIB-4 to liver biopsy in ruling out cirrhosis in NAFLD patients at a tertiary, transplant referral center in the US. METHODS: We retrospectively evaluated 93 patients with a mean age of 53 years (SD: 13 years) who underwent liver ultrasound elastography and liver biopsy, and additionally calculated their FIB-4 at the time of biopsy. We compared the liver stiffness measurement (LSM) obtained from ultrasound elastography and FIB-4 with the pathology results for ruling out cirrhosis. RESULTS: 85% of the patients were white, 53% were female, average BMI was 34.7 (SD: 6.7), 52% had diabetes, and 53% had hypertension. For biopsy-proven cirrhosis (prevalence 15%), a cut-off value of 12.5 kilopascals (kPa) for F4 had a sensitivity of 92% and a specificity of 54%. Values below this threshold excluded cirrhosis with 98% certainty. Compared to FIB-4, ultrasound elastography showed higher accuracy in ruling out cirrhosis (92% vs. 80% sensitivity, 98% vs. 95% negative predictive value (NPV), respectively). CONCLUSION: To our knowledge, this is the first study in a tertiary transplant referral center in the USA to show that ultrasound elastography was superior to FIB-4 and can be used as a reliable screening test to rule out cirrhosis in obese NAFLD patients at a 12.5 kPa cut-off. Therefore, helping to avoid the risk and expense associated with liver biopsy.

CK2-Dependent Phosphorylation of the Brg1 Chromatin Remodeling Enzyme Occurs during Mitosis.

Brg1 (Brahma-related gene 1) is one of two mutually exclusive ATPases that can act as the catalytic subunit of mammalian SWI/SNF (mSWI/SfigureNF) chromatin remodeling enzymes that facilitate utilization of the DNA in eukaryotic cells. Brg1 is a phospho-protein, and its activity is regulated by specific kinases and phosphatases. Previously, we showed that Brg1 interacts with and is phosphorylated by casein kinase 2 (CK2) in a manner that regulates myoblast proliferation. Here, we use biochemical and cell and molecular biology approaches to demonstrate that the Brg1-CK2 interaction occurred during mitosis in embryonic mouse somites and in primary myoblasts derived from satellite cells isolated from mouse skeletal muscle tissue. The interaction of CK2 with Brg1 and the incorporation of a number of other subunits into the mSWI/SNF enzyme complex were independent of CK2 enzymatic activity. CK2-mediated hyperphosphorylation of Brg1 was observed in mitotic cells derived from multiple cell types and organisms, suggesting functional conservation across tissues and species. The mitotically hyperphosphorylated form of Brg1 was localized with soluble chromatin, demonstrating that CK2-mediated phosphorylation of Brg1 is associated with specific partitioning of Brg1 within subcellular compartments. Thus, CK2 acts as a mitotic kinase that regulates Brg1 phosphorylation and subcellular localization.

A Compact, High-Accuracy Cas9 with a Dinucleotide PAM for In Vivo Genome Editing.

CRISPR-Cas9 genome editing has transformed biotechnology and therapeutics. However, in vivo applications of some Cas9s are hindered by large size (limiting delivery by adeno-associated virus [AAV] vectors), off-target editing, or complex protospacer-adjacent motifs (PAMs) that restrict the density of recognition sequences in target DNA. Here, we exploited natural variation in the PAM-interacting domains (PIDs) of closely related Cas9s to identify a compact ortholog from Neisseria meningitidis-Nme2Cas9-that recognizes a simple dinucleotide PAM (N4CC) that provides for high target site density. All-in-one AAV delivery of Nme2Cas9 with a guide RNA targeting Pcsk9 in adult mouse liver produces efficient genome editing and reduced serum cholesterol with exceptionally high specificity. We further expand our single-AAV platform to pre-implanted zygotes for streamlined generation of genome-edited mice. Nme2Cas9 combines all-in-one AAV compatibility, exceptional editing accuracy within cells, and high target site density for in vivo genome editing applications.

Streamlined ex vivo and in vivo genome editing in mouse embryos using recombinant adeno-associated viruses.

Recent advances using CRISPR-Cas9 approaches have dramatically enhanced the ease for genetic manipulation in rodents. Notwithstanding, the methods to deliver nucleic acids into pre-implantation embryos have hardly changed since the original description of mouse transgenesis more than 30 years ago. Here we report a novel strategy to generate genetically modified mice by transduction of CRISPR-Cas9 components into pre-implantation mouse embryos via recombinant adeno-associated viruses (rAAVs). Using this approach, we efficiently generated a variety of targeted mutations in explanted embryos, including indel events produced by non-homologous end joining and tailored mutations using homology-directed repair. We also achieved gene modification in vivo by direct delivery of rAAV particles into the oviduct of pregnant females. Our approach greatly simplifies the generation of genetically modified mice and, more importantly, opens the door for streamlined gene editing in other mammalian species.

Maternal expression and early induction of histone gene transcription factor Hinfp sustains development in pre-implantation embryos.

Fidelity of histone gene expression is important for normal cell growth and differentiation that is stringently controlled during development but is compromised during tumorigenesis. Efficient production of histones for packaging newly replicated DNA is particularly important for proper cell division and epigenetic control during the initial pre-implantation stages of embryonic development. Here, we addressed the unresolved question of when the machinery for histone gene transcription is activated in the developing zygote to accommodate temporal demands for histone gene expression. We examined induction of Histone Nuclear Factor P (HINFP), the only known transcription factor required for histone H4 gene expression, that binds directly to a unique H4 promoter-specific element to regulate histone H4 transcription. We show that Hinfp gene transcripts are stored in oocytes and maternally transmitted to the zygote. Transcripts from the paternal Hinfp gene, which reflect induction of zygotic gene expression, are apparent at the 4- to 8-cell stage, when most maternal mRNA pools are depleted. Loss of Hinfp expression due to gene ablation reduces cell numbers in E3.5 stage embryos and compromises implantation. Reduced cell proliferation is attributable to severe reduction in histone mRNA levels accompanied by reduced cell survival and genomic damage as measured by cleaved Caspase 3 and phospho-H2AX staining, respectively. We conclude that transmission of maternal Hinfp transcripts and zygotic activation of the Hinfp gene together are necessary to control H4 gene expression in early pre-implantation embryos in order to support normal embryonic development.

Contrasting roles for MyoD in organizing myogenic promoter structures during embryonic skeletal muscle development.

BACKGROUND: Among the complexities of skeletal muscle differentiation is a temporal distinction in the onset of expression of different lineage-specific genes. The lineage-determining factor MyoD is bound to myogenic genes at the onset of differentiation whether gene activation is immediate or delayed. How temporal regulation of differentiation-specific genes is established remains unclear. RESULTS: Using embryonic tissue, we addressed the molecular differences in the organization of the myogenin and muscle creatine kinase (MCK) gene promoters by examining regulatory factor binding as a function of both time and spatial organization during somitogenesis. At the myogenin promoter, binding of the homeodomain factor Pbx1 coincided with H3 hyperacetylation and was followed by binding of co-activators that modulate chromatin structure. MyoD and myogenin binding occurred subsequently, demonstrating that Pbx1 facilitates chromatin remodeling and modification before myogenic regulatory factor binding. At the same time, the MCK promoter was bound by HDAC2 and MyoD, and activating histone marks were largely absent. The association of HDAC2 and MyoD was confirmed by co-immunoprecipitation, proximity ligation assay (PLA), and sequential ChIP. CONCLUSIONS: MyoD differentially promotes activated and repressed chromatin structures at myogenic genes early after the onset of skeletal muscle differentiation in the developing mouse embryo.

Obtención de microcápsulas de tamaño controlado conteniendo Lactococcus lactis, utilizando mezclas de gelanos de alto y bajo acilo / Obtaining size-controlled microcapsules by ionic gelation with high and low acyl gellans containing Lactococcus lactis

Control the diameter of microcapsules obtained with functional biopolymer is a crucial parameter in the success of food applications, since it affects the protection of microencapsulated microorganism and also in the texture of the final product. The aim of this study was to assess the obtaining of controlled size microcapsules containing Lactococcus lactis, using mixtures of high acyl gellan (HA) and low acyl gellan (LA). A concentration of 0.2% (w/w) gellan was employed using a simple design, generating the following mixtures: 100HA/0.0LA, 0.0HA/100LA, 25HA/75LA, 50HA/50LA and 75HA/25LA. The diameter of the microcapsules, efficiency of microencapsulation and viability of the microencapsulated microorganism were studied in function of the speed of agitation (400-800 rpm) and surfactant concentration (sorbitan monooleate) (0.0-0.2%)v/v. The results indicated that mixtures with concentration equal or greater than 50% of HA gellan are not efficient for obtaining microcapsules, only the LA gellan and the mixture 25HA/75LA gave acceptable results. The viability of the microorganism and the efficiency of microencapsulation were descending function of the stirring speed and surfactant concentration. The microcapsules obtained had diameters not greater than 80 µm when the highest concentrations of surfactant (0.2% v/v) and stirring speed (800 rpm) were used, suggesting that the ionic gelation can be used to obtain microcapsules of controlled size (15-75 µm) containing Lactococcus lactis with high viability (83.32%) and high efficiency of microencapsulation (82.4%), which makes it feasible for use in food applications.

Controlar el diámetro de microcápsulas obtenidas con biopolímeros funcionales es un parámetro crucial en el éxito de aplicaciones alimentarias, ya que influye en la protección del microorganismo microencapsulado y también en la textura del producto final. El objetivo de este trabajo fue evaluar la obtención de microcápsulas de tamaño controlado conteniendo Lactococcus lactis, utilizando mezclas de gelana de alto (HA) y bajo acilo (LA). Se empleó una concentración de gelana de 0.2% p/p usando un diseño de mezclas simple, generando las siguientes mezclas, 100HA/0.0LA, 0.0HA/100LA, 25HA/75LA, 50HA/50LA, 75HA/25LA. El diámetro de las microcápsulas, la eficiencia de microencapsulación y la viabilidad del microorganismo microencapsulado fueron estudiadas en función de la velocidad de agitación (400-800 rpm) y concentración de surfactante (sorbitan monooleate) (0.0-0.2%)v/v. Los resultaron indicaron que las mezclas con concentración igual o superior al 50% de gelana de HA, no son eficientes para obtener microcápsulas; solamente dieron resultados aceptables la gelana de LA y la mezcla 25HA/75LA. La viabilidad del microorganismo y la eficiencia de microencapsulación variaron en función descendente de la velocidad de agitación y concentración de surfactante. Las microcápsulas obtenidas no presentaron diámetros superiores a 80 µm cuando se emplearon las mayores concentraciones de surfactante (0.2%) y velocidad de agitación (800 rpm), sugiriendo que la gelación iónica puede ser utilizada para obtener microcápsulas de tamaño controlado (15-75 µm) conteniendo Lactococcus lactis con alta viabilidad (83.32%) y eficiencia de microencapsulación (82.4%), cuando se utiliza la mezcla 25HA/75LA a 800 rpm y 0.2% v/v de surfactante, lo cual la hace factible para su uso en aplicaciones alimentarias.

Conditional Aurora A deficiency differentially affects early mouse embryo patterning.

Aurora A is a mitotic kinase essential for cell proliferation. In mice, ablation of Aurora A results in mitotic arrest and pre-implantation lethality, preventing studies at later stages of development. Here we report the effects of Aurora A ablation on embryo patterning at early post-implantation stages. Inactivation of Aurora A in the epiblast or visceral endoderm layers of the conceptus leads to apoptosis and inhibition of embryo growth, causing lethality and resorption at approximately E9.5. The effects on embryo patterning, however, depend on the tissue affected by the mutation. Embryos with an epiblast ablation of Aurora A properly establish the anteroposterior axis but fail to progress through gastrulation. In contrast, mutation of Aurora A in the visceral endoderm, leads to posteriorization of the conceptus or failure to elongate the anteroposterior axis. Injection of ES cells into Aurora A epiblast knockout blastocysts reconstitutes embryonic development to E9.5, indicating that the extra-embryonic tissues in these mutant embryos can sustain development to organogenesis stages. Our results reveal new ways to induce apoptosis and to ablate cells in a tissue-specific manner in vivo. Moreover, they show that epiblast-ablated embryos can be used to test the potency of stem cells.

A non-specific effect associated with conditional transgene expression based on Cre-loxP strategy in mice.

Transgenes flanked by loxP sites have been widely used to generate transgenic mice where the transgene expression can be controlled spatially and temporally by Cre recombinase. Data from this approach has led to important conclusions in cancer, neurodevelopment and neurodegeneration. Using this approach to conditionally express micro RNAs (miRNAs) in mice, we found that Cre-mediated recombination in neural progenitor cells caused microcephaly in five of our ten independent transgenic lines. This effect was not associated with the types or the quantity of miRNAs being expressed, nor was it associated with specific target knockdown. Rather, it was correlated with the presence of multiple tandem transgene copies and inverted (head-to-head or tail-to-tail) transgene repeats. The presence of these inverted repeats caused a high level of cell death in the ventricular zone of the embryonic brain, where Cre was expressed. Therefore, results from this Cre-loxP approach to generate inducible transgenic alleles must be interpreted with caution and conclusions drawn in previous reports may need reexamination.

Influencia de la ingesta de bebidas con diferente osmolaridad, sobre el tipo de deshidratación y las concentraciones de electrolitos, plasmáticos y urinarios, durante una actividad física de alta intensidad y larga duración / Effect of beverage osmolarity on dehydration type and plasmatic and urinary electrolytic concentrations during a high-intensity, long-lasting physical activity

Objetivo: establecer los efectos sobre la osmolalidad y las concentraciones electrolíticas, plasmáticas y urinarias, del consumo de tres bebidas con diferente osmolaridad después de una actividad física de alta intensidad y larga duración. Métodos: nueve corredores de fondo realizaron 88 minutos de carrera en banda rodante, seguidos de 90 minutos de recuperación; inicialmente, sin reposición hídrica –procedimiento deshidratado– (DH); luego, tres procedimientos secuenciales y aleatorios ingiriendo un volumen similar de una de tres bebidas, isoosmolar, hipoosmolar o hiperosmolar –procedimientos con hidratación (RH)–. Los electrolitos, plasmáticos y urinarios, la osmolalidad plasmática y la osmolaridad urinaria se midieron antes y después de la carrera y al final de la recuperación. Resultados: en DH, al final del ejercicio, se observó una deshidratación hipernatrémica e hiperclorémica (p < 0,05); durante todo el procedimiento hubo hipercaliemia (p < 0,011); al final de la recuperación hubo reducción del volumen urinario (p < 0,05) e hipercaliuria (p < 0,001). La reposición parcial de las pérdidas hídricas atenuó la deshidratación y los cambios plasmáticos del sodio y el cloro pero no los del potasio al final del ejercicio. Todas las variables estudiadas se asociaron con la duración de la actividad física (p < 0,03). Hubo correlaciones, con todos los tratamientos, durante todo el procedimiento, entre el sodio y el cloro plasmáticos (r: 0,85-0,96) y entre la osmolaridad y el sodio urinarios (r: 0,50-0,83). Conclusiones: al final de la actividad física se observó en el grupo DH una deshidratación hipernatrémica, hiperclorémica e hipercaliémica; la reposición parcial de las pérdidas hídricas, en el límite inferior de lo recomendado, atenuó la deshidratación y los cambios de los electrolitos plasmáticos excepto los del potasio. Son pocas las investigaciones que emplean un modelo de mediciones secuenciales, doble ciego, como el utilizado en el presente trabajo.

Objetive: To establish the effects on plasma osmolality and serum and urine electrolyte composition of the intake of three beverages with different osmolarities after a high intensity, long duration run in endurance athletes. Methodology: Nine long-distance runners performed 88 minutes of running on a treadmill (1% of inclination at a speed equivalent to 80% of the reserve heart rate), followed by 90 minutes of recovery; at the beginning there was no fluid replacement –dehydrated treatment–(DH); later on three sequential and randomizedprocedures were used, drinking equal volumes of one ofthree beverages, namely: hyperosmolar (Hyper),hyposmolar (Hypo) and isosmolar (Iso). Plasmaticosmolality and urinary osmolarity were measured bymeans of standard laboratory techniques, before andafter the running period.Results: In DH, at the end of the exercise period, ahypernatremic and hyperchloremic dehydration wasobserved (p < 0.05); throughout the procedure there washyperkaliemia (p < 0.011); at the end of the recoveryperiod there were an urinary volume reduction (p <0.05) and hyperkaliuria (p < 0.001). Partial replacement of the water loss, with beverages of different osmolarity,attenuated dehydration and the plasmatic changes ofsodium and chloride, but not those of potassium at theend of the exercise period, or those of urinary potassium at the end of the recovery period. All studied variables, except for the urinary concentration of chlorine, were associated with the duration of the physical activity (p < 0.03); only the weight loss showed time-treatment association (p < 0.001). There were correlations with all treatments and during all procedures between plasmatic sodium and chloride (r: 0.85-0.96) and between urinary osmolarity and sodium (r: 0.50-0.83). Conclusions: At the end of the physical activity there was, in the DH group, a hypernatremic, hyperchloremic and hyperkaliemic type of dehydration; partial replacement of the water loss, although in the lower level of the recommended volume, attenuated dehydration and the plasmatic electrolytic changes, except for those of the potassium; hyperkaliuria did not change either at the end of the procedure. Few investigations have used the double-blinded model of sequential measurements that was used in the present work.

Aurora-A kinase is essential for bipolar spindle formation and early development.

Aurora-A is a conserved kinase implicated in mitotic regulation and carcinogenesis. Aurora-A was previously implicated in mitotic entry and spindle assembly, although contradictory results prevented a clear understanding of the roles of Aurora-A in mammals. We developed a conditional null mutation in the mouse Aurora-A gene to investigate Aurora-A functions in primary cells ex vivo and in vivo. We show here that conditional Aurora-A ablation in cultured embryonic fibroblasts causes impaired mitotic entry and mitotic arrest with a profound defect in bipolar spindle formation. Germ line Aurora-A deficiency causes embryonic death at the blastocyst stage with pronounced cell proliferation failure, mitotic arrest, and monopolar spindle formation. Aurora-A deletion in mid-gestation embryos causes an increase in mitotic and apoptotic cells. These results indicate that murine Aurora-A facilitates, but is not absolutely required for, mitotic entry in murine embryonic fibroblasts and is essential for centrosome separation and bipolar spindle formation in vitro and in vivo. Aurora-A deletion increases apoptosis, suggesting that molecular therapies targeting Aurora-A may be effective in inducing tumor cell apoptosis. Aurora-A conditional mutant mice provide a valuable system for further defining Aurora-A functions and for predicting effects of Aurora-A therapeutic intervention.

Influencia de la ingesta ad libitum de bebidas con diferente osmolaridad sobre algunas variables fisiológicas durante una actividad física de alta intesidad y larga duración / Influence of ad libitum intake of beverages with diferent osmolarities on some physiological parameters during a high-intensity, long-duration physical activity

OBJETIVO: establecer la influencia de la ingesta ad libitum de diferentes bebidas hidratantes sobre el porcentaje de pérdida del peso corporal (PC), el aumento de la frecuencia cardíaca (FC) y la reducción porcentual del volumen plasmático (porcentaje VP) en deportistas sometidos a una actividad física de alta intensidad y larga duración. METODOLOGÍA: luego de nueve minutos de calentamiento, en banda rodante con velocidad equivalente al 50 por ciento de la frecuencia cardíaca de reserva (FCR), siguieron 88 minutos de carrera, durante la cual la velocidad se incrementó al 80 por ciento de la FCR; al final, 90 minutos de recuperación. No se hizo reposición hídrica durante el tratamiento deshidratado (DH); durante los tratamientos con hidratación se emplearon volúmenes similares, ingeridos ad libitum, de cada una de tres bebidas, a saber: hiperosmolar (Hiper), hipoosmolar (Hipo) e isoosmolar (Iso). RESULTADOS: se observó en cada uno de los tratamientos un aumento del porcentaje de pérdia del peso corporal (PC) (p<0,001) y de la FC (p< 0,05) al igual que una correlación entre el porcentaje PC y el incremento de la FC (p<0,000); en los tratamientos DH e Hiper hubo una reducción del volumen plasmático (VP) (p<0,05). Se observó interacción tiempo tratamiento con el porcentaje PC. CONCLUSIONES: la ingesta ad libitum fue menor que la cantidad recomendada en la literatura internacional, por lo que, probablemente, no se pudieron establecer los efectos de la osmolaridad de las bebidas hidratantes sobre las variables estudiadas. La magnitud del porcentaje PC, del incremento de la FC y de la reducción del porcentaje VP fueron proporcionales a la duración de la actividad física; la relación existente entre el porcentaje PC y la porcentaje VP se modificó por la osmolaridad de la bebida.

OBJETIVE: To establish the influence of ad libitum intake of hydrating beverages with different osmolarities on the percentage of body weight loss (%BW), the increase of heart rate (HR), and the percentage of plasma volume decrease (%PV) in athletes during a high-intensity and long-time run. METHODOLOGY: After 9 warm-up minutes on a treadmill at a speed equivalent to 50% of the heart rate reserve, the athletes performed a run at 80% of the heart rate reserve speed, followed by 90 minutes of recovery. During the "dehydrated treatment" no fluid replacement was given, but during the "hydrated treatments" similar volumes were ad libitum drunk of each of three hydrating beverages, namely hyperosmolar (Hiper), hypoosmolar (Hipo) and isoosmolar (Iso). RESULTS: In all treatments there were increases of the percentage of body weight loss (%BW) (p < 0.001) and of the HR (p < 0.05), and there was a correlation between the %BW and the increase of HR (p < 0.000); in the DH and Hyper treatments a decrease of the percentage of plasma volume loss (%PV) (p < 0.05) was observed. An interaction treatment-time with the %WB was observed. CONCLUSIONS: Ad libitum intake of rehydrating beverages was less than the amount recommended in the international literature. That may have been the reason why the effects of osmolarity of such beverages on the analyzed parameters could not be determined. The amount of the %BW, the HR increase and the %PV decrease were proportional to the duration of physical activity. The relationship between the % BW and the %PV was modified by the osmolarity of beverages

Ablation of MEKK4 kinase activity causes neurulation and skeletal patterning defects in the mouse embryo.

Skeletal disorders and neural tube closure defects represent clinically significant human malformations. The signaling networks regulating normal skeletal patterning and neurulation are largely unknown. Targeted mutation of the active site lysine of MEK kinase 4 (MEKK4) produces a kinase-inactive MEKK4 protein (MEKK4(K1361R)). Embryos homozygous for this mutation die at birth as a result of skeletal malformations and neural tube defects. Hindbrains of exencephalic MEKK4(K1361R) embryos show a striking increase in neuroepithelial cell apoptosis and a dramatic loss of phosphorylation of MKK3 and -6, mitogen-activated protein kinase kinases (MKKs) regulated by MEKK4 in the p38 pathway. Phosphorylation of MAPK-activated protein kinase 2, a p38 substrate, is also inhibited, demonstrating a loss of p38 activity in MEKK4(K1361R) embryos. In contrast, the MEK1/2-extracellular signal-regulated kinase 1 (ERK1)/ERK2 and MKK4-Jun N-terminal protein kinase pathways were unaffected. The p38 pathway has been shown to regulate the phosphorylation and expression of the small heat shock protein HSP27. Compared to the wild type, MEKK4(K1361R) fibroblasts showed significantly reduced phosphorylation of p38 and HSP27, with a corresponding heat shock-induced instability of the actin cytoskeleton. Together, these data demonstrate MEKK4 regulation of p38 and that substrates downstream of p38 control cellular homeostasis. The findings are the first demonstration that MEKK4-regulated p38 activity is critical for neurulation.

Cambios en algunas variables hematológicas, en un grupo de mujeres mayores de 55 años, luego de un programa de entrenamiento aeróbico / Changes in some hematologic variables in a group of women older Than 55 years, after a program of aerobic training

Esta investigación fue realizada con el auspicio del Comité para el desarrollo de la investigación de la Universidad de Antioquia (CODI) e Indeportes Antioquia.Objetivo: determinar los cambios en algunas variables hematológicas luego de un programa de actividad física aeróbica, por un período de cuatro meses, en un grupo de mujeres sedentarias sanas mayores de 55 años.Método: se estudiaron 14 mujeres mayores de 55 años, sedentarias, sanas, a quienes se les realizó un programa de actividad física aeróbica tres días a la semana, durante cuatro meses consecutivos, con una intensidad entre el 60 y el 85 por ciento de la FCmax y una duración de 60 minutos. Antes y después del programa de actividad física se obtuvieron muestras de sangre para evaluar el comportamiento de la hemoglobina (Hb), el hematocrito (Hct), el recuento de glóbulos rojos, el volumen corpuscular medio (VCM), la hemoglobina corpuscular media (HCM) y la concentración de hemoglobina corpuscular media (CHCM); mediante una prueba máxima, se realizó la medición del consumo máximo de oxígeno. Resultados: se observó un incremento estadísticamente significativo de la Hb (p<0.01),el Hct (p<0.01), el VCM (p<0.001), la HCM (p<0.001) y el VO2max (p<0.05). No hubo cambio en el recuento de glóbulos rojos ni en la CHCM. Conclusión: un programa de actividad física regular, a intensidades entre el 60 y el 85 por ciento de la frecuencia cardíaca máxima, en la población estudiada, incrementó los valores de la hemoglobina y del hematocrito, lo que sugiere que el entrenamiento aeróbico mejora el aporte de oxígeno hacia los tejidos.

Objective: to evaluate changes in some hematologic variables after a four-month program of aerobic physical activity, in a group of healthy women, older than 55 years. Methods: 14 healthy sedentary women, older than 55 years were studied; they participated in a program of aerobic physical activity, three times per week, during four months, with an intensity between 60-85% of the maximal heart rate and with 60 minutes of duration per session. Before and after the program blood specimens were obtained to evaluate changes of hemoglobin, hematocrite, red blood cells count, average corpuscular volume, average corpuscular hemoglobin, and average concentration of corpuscular hemoglobin; by means of a maximal test in treadmill the maximal oxygen uptake (VO2max) was determined. Results: significant increase was found in hemoglobin (p<0.01), hematocrite (p<0.001), average corpuscular volume (p<0.001), average corpuscular hemoglobin (p<0.01) and VO2max (p<0.05). There were no changes in red blood cell count and average concentration of corpuscular hemoglobin. Conclusion: in the studied group, a program of regular physical activity, with an intensity between 60-85% of the maximal heart rate, increased hemoglobin and hematocrite. This results suggest that aerobic training increases the transport of oxygen to tissues.

Análisis molecular de la hemofilia A en familias del noroeste de México / molecular analysis of Hemophilia A in northeastern mexican families

Empleando las técnicas de Southern para la detección de genes por hibridación con una sonda radiactiva de la reacción en cadena de la polimerasa para la amplificación de fragmentos génicos, se practicó el análisis molecular a nivel de ADN para detectar portadoras de la hemofilia A. Este se basó en el estudio del polimorfismo para la enzima de restricción Bcl I presente en el intró 18 del gen para el factor VIII de la coagulación. Se analizaron ocho familias de noroeste de México con antecedentes de la enfermedad, que comprendieron un total de 43 individuos. De las 27 mujeres que formaban parte de la muestra, 17 requerían el diagnóstico de portadora, el cual se estableció en tres de ellas, se excluyó en cinco y no se pudo determinar en nueve. Las frecuencias encontradas en la muestra para el polimorfismo fueron de 63 por ciento para el alelo de tamaño y de 37 por ciento para el alelo de tamaño menor, determinando un porcentaje de mujeres heterocigotas (informativas) de 48.2 por ciento y fijando en este valor la utilidad teórica del polimorfismo en las familias aquí incluidas. Estas frecuencias muestran simulitud con las de las poblaciones mediterráneas y establecen que la utilidad del polimorfismo es mayor en nuestra muestra que en otros grupos étnicos.