Viscoelastic materials are most energy efficient when loaded and unloaded at equal rates.

Biological springs can be used in nature for energy conservation and ultra-fast motion. The loading and unloading rates of elastic materials can play an important role in determining how the properties of these springs affect movements. We investigate the mechanical energy efficiency of biological springs (American bullfrog plantaris tendons and guinea fowl lateral gastrocnemius tendons) and synthetic elastomers. We measure these materials under symmetric rates (equal loading and unloading durations) and asymmetric rates (unequal loading and unloading durations) using novel dynamic mechanical analysis measurements. We find that mechanical efficiency is highest at symmetric rates and significantly decreases with a larger degree of asymmetry. A generalized one-dimensional Maxwell model with no fitting parameters captures the experimental results based on the independently characterized linear viscoelastic properties of the materials. The model further shows that a broader viscoelastic relaxation spectrum enhances the effect of rate-asymmetry on efficiency. Overall, our study provides valuable insights into the interplay between material properties and unloading dynamics in both biological and synthetic elastic systems.

The effects of temperature on elastic energy storage and release in a system with a dynamic mechanical advantage latch.

Changes in temperature alter muscle kinetics and in turn affect whole-organism performance. Some organisms use the elastic recoil of biological springs, structures which are far less temperature sensitive, to power thermally robust movements. For jumping frogs, the use of elastic energy in tendons is facilitated through a geometric latching mechanism that operates through dynamic changes in the mechanical advantage (MA) of the hindlimb. Despite the well-documented use of elastic energy storage, frog jumping is a locomotor behavior that is significantly affected by changes in temperature. Here, we used an in vitro muscle preparation interacting in real time with an in silico model of a legged jumper to understand how changes in temperature affect the flow of energy in a system using a MA latch. We used the plantaris longus muscle-tendon unit (MTU) to power a virtual limb with changing MA and a mass being accelerated through a real-time feedback controller. We quantified the amount of energy stored in and recovered from elastic structures and the additional contribution of direct muscle work after unlatching. We found that temperature altered the duration of the energy loading and recovery phase of the in vitro/in silico experiments. We found that the early phase of loading was insensitive to changes in temperature. However, an increase in temperature did increase the rate of force development, which in turn allowed for increased energy storage in the second phase of loading. We also found that the contribution of direct muscle work after unlatching was substantial and increased significantly with temperature. Our results show that the thermal robustness achieved by an elastic mechanism depends strongly on the nature of the latch that mediates energy flow, and that the relative contribution of elastic and direct muscle energy likely shapes the thermal sensitivity of locomotor systems.

Characterizing Neurocognitive Impairment in Juvenile Fibromyalgia Syndrome: Subjective and Objective Measures of Dyscognition.

Objectives: Our understanding of brain fog, or dyscognition, among youth with juvenile fibromyalgia syndrome is limited. We aimed to determine the prevalence of subjective (self-reported) and objective dyscognition, as well as factors associated with subjective dyscognition in juvenile fibromyalgia syndrome. Methods: A cross-sectional cohort study of patients (n = 31) 12-17 years old diagnosed with primary juvenile fibromyalgia syndrome and one of their parents from 2017 to 2019. Subjects completed a series of survey measures and patients completed a brief neurocognitive battery. Subjective dyscognition was determined based on scores on the Pediatric Quality of Life Inventory (PedsQL) Cognitive Functioning Scale and Behavior Rating Inventory of Executive Function (BRIEF-2) global executive composite (GEC). Objective dyscognition was defined as impairment of more than two standard deviations in any of the neurocognitive domains. We used Fisher's exact test or Wilcoxon rank-sum test, as appropriate, to compare clinical patients based on the presence of dyscognition. Multivariable logistic regression modeling was performed to determine factors associated with subjective dyscognition. Results: Of the 31 subjects, 65% reported subjective dyscognition and 39% had objective dyscognition, primarily in the domains of psychomotor speed (23%), executive function (23%), and attention (3%). Subjective dyscognition was not indicative of objective dyscognition. Subjective dyscognition was independently associated with functional disability (OR: 1.19 [95% CI: 1.02-1.40]) and anxiety (OR: 1.12 [95% CI: 1.02-1.24]). Discussion: Adolescents with fibromyalgia predominantly experience subjective dyscognition but more than 1/3 also experience objective dyscognition. Future research should explore the impact of interdisciplinary rehabilitation programs on the treatment of dyscognition in youth with JFMS.

Temporal Relationship Between Juvenile Idiopathic Arthritis Disease Activity and Uveitis Disease Activity.

OBJECTIVE: To determine whether there is a temporal association between arthritis and uveitis activity among children with juvenile idiopathic arthritis-associated uveitis (JIA-U). METHODS: Uveitis and arthritis data from patients with JIA-U age ≤21 years were collected from July 2013 to December 2019 at a tertiary care center. Arthritis activity was assessed at each rheumatology visit, and the primary outcome was the presence of active uveitis at ophthalmologic examination within 45 days of the rheumatology visit. Repeated-measures logistic regression was used to evaluate the temporal association between any uveitis activity within 45 days of arthritis activity. Models were adjusted for demographic-, disease-, and treatment-related factors. RESULTS: A total of 98 patients were included: 81 (83%) female, 67 (69%) antinuclear antibody positive, 59 (60%) oligoarticular, and 13 (13%) enthesitis-related arthritis (ERA) subtypes. There were 1,229 rheumatology visits, with a median of 13 visits per patient (interquartile range 7-18). Concordance between arthritis and uveitis activity was observed 73% of the time (694 of 947). There was an independent temporal association between uveitis and arthritis activity (odds ratio 2.47 [95% confidence interval 1.72-3.54]; P < 0.01), adjusted for demographic and disease characteristics. Use of combination biologic and nonbiologic disease-modifying antirheumatic drugs, female sex, HLA-B27 positivity, and ERA and polyarticular (rheumatoid factor negative) subtypes were associated with decreased odds of active uveitis at any time point. CONCLUSION: In patients with JIA-U, there is a significant temporal association between arthritis and uveitis disease activity. These novel results suggest that an arthritis flare should prompt an expedited referral to the ophthalmologist.

Caracterización epidemiológica de los pacientes con sospecha clínica y diagnóstico de arbovirosis en Granma durante el 2019 / Epidemiological characterization of patients with clinical suspicion and diagnosis of arbovirus in Granma province during 2019

Introducción: Las enfermedades arbovirales presentan un eleva incidencia y constituyen una amenaza permanente para la salud a escala mundial. Objetivo: Caracterizar epidemiológicamente los pacientes con sospecha clínica y diagnóstico de arbovirosis en la provincia Granma durante el 2019. Métodos: Se realizó un estudio observacional, descriptivo, transversal en el periodo comprendido entre el primero de enero y el 31 de diciembre de 2019. Las variables estudiadas fueron: edad, sexo, municipios, formas de identificación de signos y síntomas, positividad a dengue y meses de estudio de los pacientes. Resultados: En los casos estudiados por sospechas, el 41,43 por ciento pertenecía al municipio Bayamo y el 51,85 por ciento (9180) fueron pacientes femeninas. El rango de edad predominante fue ≤ 20 años (n = 8340; 47,10 por ciento). En el 87,07 por ciento (15417) de los pacientes la identificación de signos y síntomas sugerentes de arbovirosis fue mediante las pesquisas. La positividad a dengue se encontró en el 25,00 por ciento de los pacientes (4427), de los cuales el 53,87 por ciento (2385) fueron pacientes femeninas. El rango de edad más afectado por la arbovirosis fue el de 41-60 (n = 1422; 32,12 por ciento). El mes de septiembre fue el de mayor número de casos tanto estudiados por sospechas (n = 3720; 21,01 por ciento) como confirmados con dengue (n = 1341; 30,29 por ciento). En la provincia, la tasa de incidencia del dengue fue de 54,0 por cada 10 mil habitantes. Conclusiones: Se evidenció la importancia de las pesquisas como método para identificar signos y síntomas sugerentes de enfermedades arbovirales. Las tasas de incidencia calculadas señalaron a los territorios más afectados por dengue, lo cual constituye un punto de partida para la implementación de estrategias de salud enfocadas en la prevención arboviral(AU)

Introduction: Arboviral diseases have a high incidence and constitute a permanent threat to health globally. Objective: Characterize from the epidemiological perspective patients with clinical suspicion and diagnosis of arbovirus in Granma province during 2019. Methods: An observational, descriptive, cross-sectional study was conducted in the period between January 1st and December 31st, 2019. The variables studied were: age, sex, municipalities, ways of identifying signs and symptoms, dengue positivity and months of study of patients. Results: In the cases studied due to suspicions, 41.43 percent belonged to Bayamo municipality and 51.85percent (9180) were female patients. The predominant age range was ≤ 20 years (n = 8340; 47.10percent). In 87.07percent (15417) of patients, the identification of signs and symptoms suggestive to arbovirus was through investigations. Dengue positivity was found in 25.00 percent of patients (4427), of which 53.87percent (2385) were female patients. The age range most affected by arbovirus was 41-60 (n = 1422; 32.12percent). September was the month with the highest number of cases both studied by suspicions (n = 3720; 21.01percent) and confirmed with dengue (n = 1341; 30.29percent). In the province, the incidence rate of dengue was 54.0 per 10,000 inhabitants. Conclusions: The importance of the investigations as a method to identify signs and symptoms suggestive to arboviral diseases was evidenced. The calculated incidence rates indicated the most affected territories by dengue, which constitutes a starting point for the implementation of health strategies focused on arboviral prevention(AU)

Tuned muscle and spring properties increase elastic energy storage.

Elastic recoil drives some of the fastest and most powerful biological movements. For effective use of elastic recoil, the tuning of muscle and spring force capacity is essential. Although studies of invertebrate organisms that use elastic recoil show evidence of increased force capacity in their energy loading muscle, changes in the fundamental properties of such muscles have yet to be documented in vertebrates. Here, we used three species of frogs (Cuban tree frogs, bullfrogs and cane toads) that differ in jumping power to investigate functional shifts in muscle-spring tuning in systems using latch-mediated spring actuation (LaMSA). We hypothesized that variation in jumping performance would result from increased force capacity in muscles and relatively stiffer elastic structures, resulting in greater energy storage. To test this, we characterized the force-length property of the plantaris longus muscle-tendon unit (MTU), and quantified the maximal amount of energy stored in elastic structures for each species. We found that the plantaris longus MTU of Cuban tree frogs produced higher mass-specific energy and mass-specific forces than the other two species. Moreover, we found that the plantaris longus MTU of Cuban tree frogs had higher pennation angles than the other species, suggesting that muscle architecture was modified to increase force capacity through packing of more muscle fibers. Finally, we found that the elastic structures were relatively stiffer in Cuban tree frogs. These results provide a mechanistic link between the tuned properties of LaMSA components, energy storage capacity and whole-system performance.

Effectiveness and toxicity of adjuvant chemotherapy in patients with non-small cell lung cancer.

OBJECTIVE: Adjuvant chemotherapy (AC) improves survival of patients with resected non-small cell lung cancer (NSCLC). However, the cisplatin-vinorelbine regimen has been associated with a significant risk of clinically relevant toxicity. We sought to evaluate the effectiveness, safety, and feasibility of AC for NSCLC patients in a real-world setting. METHODS: This was a single-center, retrospective cohort study of patients with stage I-III NSCLC undergoing surgery with curative intent between 2009 and 2018. AC was administered at the discretion of physicians. The patients were divided into two groups: AC group and no AC (control) group. Study outcomes included overall survival (OS) and recurrence-free survival (RFS), as well as the safety profile and feasibility of the cisplatin-vinorelbine regimen in a real-world setting. RESULTS: The study involved 231 patients, 80 of whom received AC. Of those, 55 patients received the cisplatin-vinorelbine regimen. Survival analyses stratified by tumor stage showed that patients with stage II NSCLC in the AC group had better RFS (p = 0.036) and OS (p = 0.017) than did those in the no AC group. Among patients with stage III NSCLC in the AC group, RFS was better (p < 0.001) and there was a trend toward improved OS (p = 0.060) in comparison with controls. Of those who received the cisplatin-vinorelbine regimen, 29% had grade 3-4 febrile neutropenia, and 9% died of toxicity. CONCLUSIONS: These results support the benefit of AC for NSCLC patients in a real-world setting. However, because the cisplatin-vinorelbine regimen was associated with alarming rates of toxicity, more effective and less toxic alternatives should be investigated.

Effectiveness and toxicity of adjuvant chemotherapy in patients with non-small cell lung cancer / Eficácia e toxicidade da quimioterapia adjuvante em pacientes com câncer de pulmão de células não pequenas

ABSTRACT Objective: Adjuvant chemotherapy (AC) improves survival of patients with resected non-small cell lung cancer (NSCLC). However, the cisplatin-vinorelbine regimen has been associated with a significant risk of clinically relevant toxicity. We sought to evaluate the effectiveness, safety, and feasibility of AC for NSCLC patients in a real-world setting. Methods: This was a single-center, retrospective cohort study of patients with stage I-III NSCLC undergoing surgery with curative intent between 2009 and 2018. AC was administered at the discretion of physicians. The patients were divided into two groups: AC group and no AC (control) group. Study outcomes included overall survival (OS) and recurrence-free survival (RFS), as well as the safety profile and feasibility of the cisplatin-vinorelbine regimen in a real-world setting. Results: The study involved 231 patients, 80 of whom received AC. Of those, 55 patients received the cisplatin-vinorelbine regimen. Survival analyses stratified by tumor stage showed that patients with stage II NSCLC in the AC group had better RFS (p = 0.036) and OS (p = 0.017) than did those in the no AC group. Among patients with stage III NSCLC in the AC group, RFS was better (p < 0.001) and there was a trend toward improved OS (p = 0.060) in comparison with controls. Of those who received the cisplatin-vinorelbine regimen, 29% had grade 3-4 febrile neutropenia, and 9% died of toxicity. Conclusions: These results support the benefit of AC for NSCLC patients in a real-world setting. However, because the cisplatin-vinorelbine regimen was associated with alarming rates of toxicity, more effective and less toxic alternatives should be investigated.

RESUMO Objetivo: A quimioterapia adjuvante melhora a sobrevida de pacientes com câncer pulmonar de células não pequenas (CPCNP) ressecado. No entanto, o esquema cisplatina-vinorelbina está relacionado com risco significativo de toxicidade clinicamente relevante. Nosso objetivo foi avaliar a eficácia, segurança e viabilidade da quimioterapia adjuvante para pacientes com CPCNP em um cenário de mundo real. Métodos: Estudo retrospectivo de coorte realizado em um único centro com pacientes com CPCNP em estágio I-III submetidos a cirurgia com intuito curativo entre 2009 e 2018. A quimioterapia adjuvante foi administrada a critério dos médicos. Os pacientes foram divididos em dois grupos: quimioterapia adjuvante e sem quimioterapia adjuvante (grupo controle). Os desfechos estudados foram sobrevida global (SG) e sobrevida livre de recidiva (SLR), bem como o perfil de segurança e viabilidade do esquema cisplatina-vinorelbina em um cenário de mundo real. Resultados: O estudo envolveu 231 pacientes, 80 dos quais receberam quimioterapia adjuvante. Destes, 55 receberam o esquema cisplatina-vinorelbina. As análises de sobrevida estratificadas pelo estágio do tumor mostraram que os pacientes com CPCNP em estágio II que receberam quimioterapia adjuvante apresentaram melhor SLR (p = 0,036) e SG (p = 0,017) do que os do grupo controle. Entre os pacientes com CPCNP em estágio III que receberam quimioterapia adjuvante, a SLR foi melhor (p < 0,001) e houve uma tendência a melhor SG do que no grupo controle (p = 0,060). Dos que receberam o esquema cisplatina-vinorelbina, 29% apresentaram neutropenia febril de grau 3-4, e 9% morreram em virtude de toxicidade. Conclusões: Os resultados confirmam o efeito benéfico da quimioterapia adjuvante em pacientes com CPCNP em um contexto real. No entanto, o esquema cisplatina-vinorelbina relacionou-se com taxas alarmantes de toxicidade e alternativas mais eficazes e menos tóxicas devem ser investigadas.

Caracterización de pacientes con sospecha de arbovirosis atendidos en un policlínico de Jiguaní, Granma / Characterization of patients with suspected arbovirus infection cared for at a polyclinic in Jiguaní, Granma

Introducción: Las enfermedades producidas por arbovirus son un problema grave a nivel mundial. Objetivo: Caracterizar los pacientes estudiados por sospecha de arbovirosis en una institución de salud. Métodos: Se realizó un estudio observacional, descriptivo y transversal en el policlínico Edor de los Reyes Martínez Áreas del municipio Jiguaní, provincia Granma, en el periodo comprendido entre el 1 de enero y el 31 de diciembre de 2019. Se trabajó con una muestra de 2947 personas y se estudiaron las siguientes variables: edad, sexo, consejos populares, forma de identificación de signos/síntomas, diagnóstico inicial y positividad a dengue. Resultados: El 40,07 por ciento de los casos estudiados pertenece al consejo popular Jiguaní Norte. Fueron pacientes femeninas 1590 (53,95 por ciento). El rango de edad predominante fue 41-60 años (n = 1222; 41,47 por ciento). En 1908 (64,74 por ciento) pacientes la identificación de signos y síntomas sugerentes de arbovirosis fue mediante las pesquisas. El 98,88 por ciento de los pacientes (n = 2914) fue diagnosticado inicialmente con síndrome febril inespecífico. La única arbovirosis identificada fue el dengue, el que se encontró en 637 pacientes. Octubre fue el mes con mayor número de pacientes estudiados (n = 1063; 36,07 por ciento). Conclusiones: La mayoría de los casos pertenecía al sexo femenino y a la zona urbanizada del municipio. El consejo popular urbano Jiguaní Norte fue el que más casos positivos a dengue aportó(AU)

Introduction: Arbovirus infections are a serious global health problem. Objective: Characterize the patients studied for suspected arbovirus infection at a health institution. Methods: A cross-sectional observational descriptive study was conducted at Edor de los Reyes Martínez Arias polyclinic in the municipality of Jiguaní, province of Granma, from 1 January to 31 December 2019. The study sample was 2947 people, and the variables examined were age, sex, people's council, form of sign / symptom identification, initial diagnosis and positivity for dengue. Results: Of the cases studied, 40.07 percent were from the people's council of Jiguaní Norte. 1590 patients were female (53.95 percent). The prevailing age group was 41-60 years (n = 1222; 41.47 percent). In 1908 patients (64.74 percent) signs and symptoms suggesting arbovirus infection were identified through screening. 98.88 percent of the patients (n = 2914) were initially diagnosed with unspecific febrile syndrome. The only arbovirus infection identified was dengue, which was detected in 637 patients. October was the month when the highest number of patients were studied (n = 1063; 36.07 percent). Conclusions: Most cases were female and from urbanized areas in the municipality. Jiguaní Norte urban people's council contributed the most dengue positive cases(AU)

Cancer cells with defective oxidative phosphorylation require endoplasmic reticulum-to-mitochondria Ca2+ transfer for survival.

Spontaneous Ca2+ signaling from the InsP3R intracellular Ca2+ release channel to mitochondria is essential for optimal oxidative phosphorylation (OXPHOS) and ATP production. In cells with defective OXPHOS, reductive carboxylation replaces oxidative metabolism to maintain amounts of reducing equivalents and metabolic precursors. To investigate the role of mitochondrial Ca2+ uptake in regulating bioenergetics in these cells, we used OXPHOS-competent and OXPHOS-defective cells. Inhibition of InsP3R activity or mitochondrial Ca2+ uptake increased α-ketoglutarate (αKG) abundance and the NAD+/NADH ratio, indicating that constitutive endoplasmic reticulum (ER)-to-mitochondria Ca2+ transfer promoted optimal αKG dehydrogenase (αKGDH) activity. Reducing mitochondrial Ca2+ inhibited αKGDH activity and increased NAD+, which induced SIRT1-dependent autophagy in both OXPHOS-competent and OXPHOS-defective cells. Whereas autophagic flux in OXPHOS-competent cells promoted cell survival, it was impaired in OXPHOS-defective cells because of inhibition of autophagosome-lysosome fusion. Inhibition of αKGDH and impaired autophagic flux in OXPHOS-defective cells resulted in pronounced cell death in response to interruption of constitutive flux of Ca2+ from ER to mitochondria. These results demonstrate that mitochondria play a fundamental role in maintaining bioenergetic homeostasis of both OXPHOS-competent and OXPHOS-defective cells, with Ca2+ regulation of αKGDH activity playing a pivotal role. Inhibition of ER-to-mitochondria Ca2+ transfer may represent a general therapeutic strategy against cancer cells regardless of their OXPHOS status.

Lectura de palabras por personas sordas usuarias de lengua de señas mexicana / Word reading in Mexican deaf signers

El objetivo de este trabajo es determinar si las personas sordas usuarias de lengua de señas mexicana (LSM) activan la LSM en la lectura de palabras escritas en español. Se usaron pares de palabras semánticamente relacionadas y semánticamente no relacionadas, divididas a su vez 2subgrupos, fonológicamente relacionadas y fonológicamente no relacionadas en LSM. Los participantes respondieron más rápido a las palabras semánticamente y fonológicamente relacionadas, mientras que, por el contrario, respondieron más lento en las palabras semánticamente no relacionadas que sí estaban fonológicamente relacionadas. Los resultados sugieren un efecto de facilitación e interferencia, respectivamente, dado por la activación de la LSM

The goal of this study was to determine whether deaf bilingual MSL-Spanish adults activate their signed language when reading words in Spanish. Participants were Mexican Deaf signers whose dominant language was Mexican Sign Language and who had a basic Spanish written proficiency. Two main conditions were examined for word groups: semantically related and non-related words. They were also distinguished by hand "phonology": related and unrelated configurations. The written words were presented in a reaction-time task in which participants were asked to identify whether the words belonged to similar categories. Mean reaction times were faster for semantically and phonologically related and slower for semantically unrelated but phonologically related pairs. Results show that the structure of the word in Sign language is activated when reading words in Spanish

Why do Large Animals Never Actuate Their Jumps with Latch-Mediated Springs? Because They can Jump Higher Without Them.

As animals get smaller, their ability to generate usable work from muscle contraction is decreased by the muscle's force-velocity properties, thereby reducing their effective jump height. Very small animals use a spring-actuated system, which prevents velocity effects from reducing available energy. Since force-velocity properties reduce the usable work in even larger animals, why don't larger animals use spring-actuated jumping systems as well? We will show that muscle length-tension properties limit spring-actuated systems to generating a maximum one-third of the possible work that a muscle could produce-greatly restricting the jumping height of spring-actuated jumpers. Thus a spring-actuated jumping animal has a jumping height that is one-third of the maximum possible jump height achievable were 100% of the possible muscle work available. Larger animals, which could theoretically use all of the available muscle energy, have a maximum jumping height that asymptotically approaches a value that is about three times higher than that of spring-actuated jumpers. Furthermore, a size related "crossover point" is evident for these two jumping mechanisms: animals smaller than this point can jump higher with a spring-actuated mechanism, while animals larger than this point can jump higher with a muscle-actuated mechanism. We demonstrate how this limit on energy storage is a consequence of the interaction between length-tension properties of muscles and spring stiffness. We indicate where this crossover point occurs based on modeling and then use jumping data from the literature to validate that larger jumping animals generate greater jump heights with muscle-actuated systems than spring-actuated systems.

Examining the Relationship Between Parental Symptomatology and Treatment Outcomes in Children with Autism Spectrum Disorder.

This report examines the relationship between treatment response in children with ASD and parents' affective symptomatology. This study examined 29 children with ASD in a manualized group psychotherapy program, Resilience Builder Program® (RBP), where emotional and social functioning of parent and child were measured through pre- and post-treatment questionnaires. Greater parental symptomatology was associated with children's reduced response to RBP in resilience-based emotion regulation skills. Greater parental interpersonal sensitivity (ß = - .27, p = .024) predicted worse post-treatment scores in child communication skills, greater parental anxious symptoms (ß = - .45, p = .005) predicted worse post-treatment scores in child emotional control, and greater parental depressive (ß = .27, p = .041) and anxious symptoms (ß = .36, p = .004) predicted worse post-treatment scores in child internalizing problems.

Young-age onset colorectal cancer in Brazil: Analysis of incidence, clinical features, and outcomes in a tertiary cancer center.

BACKGROUND: Recent studies report increasing incidence of colorectal cancer (CRC) in the young-age population, but data concerning clinical behavior, pathologic findings, and prognosis are controversial for this group. Early recognition of CRC in young patients is a challenge and diagnosis at advanced stage is clearly associated with worse outcomes. MATERIALS AND METHODS: We retrospectively reviewed medical records of 5806 patients diagnosed with CRC between January/2011 and November/2016 and identified 781 patients aged less than 50-years-old. RESULTS: We found an absolute increasing in the incidence of CRC in patients <50 years old of 1.88%-2.23% annually, with a relative increasing of 35.3% between 2011 and 2016. Median age was 42 years, 57.4% were female and 20.9% reported family history of CRC. Left-sided tumors were more frequent and the majority of patients were symptomatic. The most common stages at diagnosis were III (34.1%) and IV (37.3%). The median overall survival (OS) for stage IV was 25 months (95% CI 20.7-29.3) and was not reached for Stages I-III (P < 0.001). Family history of CRC was independently associated with better OS in stage IV(P = 0.02). For stages I-III, wild-type KRAS, family history of CRC, and absence of angiolymphatic invasion were associated with better OS (P = 0.02, P = 0.01 and P < 0.001, respectively). CONCLUSIONS: In our cohort, the incidence of early-onset CRC is increasing over the past years. Young patients were more likely to be diagnosed with metastatic disease, left-sided and/or rectum site and symptoms at presentation. These findings highlight the emerging importance of young-age onset CRC and the need to discuss strategies to early diagnosis.

Striatal Neurodegeneration that Mimics Huntington's Disease Modifies GABA-induced Currents.

Huntington's Disease (HD) is a degenerative disease which produces cognitive and motor disturbances. Treatment with GABAergic agonists improves the behavior and activity of mitochondrial complexes in rodents treated with 3-nitropropionic acid to mimic HD symptomatology. Apparently, GABA receptors activity may protect striatal medium spiny neurons (MSNs) from excitotoxic damage. This study evaluates whether mitochondrial inhibition with 3-NP that mimics the early stages of HD, modifies the kinetics and pharmacology of GABA receptors in patch clamp recorded dissociated MSNs cells. The results show that MSNs from mice treated with 3-NP exhibited differences in GABA-induced dose-response currents and pharmacological responses that suggests the presence of GABAC receptors in MSNs. Furthermore, there was a reduction in the effect of the GABAC antagonist that demonstrates a lessening of this GABA receptor subtype activity as a result of mitochondria inhibition.

Corrigendum to "Dopaminergic Modulation of Striatal Inhibitory Transmission and Long-Term Plasticity".

[This corrects the article DOI: 10.1155/2015/789502.].

The +1858 C/T Polymorphism in the PTPN22 Gene Is Associated with Cystic Fibrosis Patients in Northeast Mexico.

Cystic fibrosis (CF) is the most common autosomal recessive disease in the Caucasian population, but it has also been widely diagnosed in the Mexican population. Production of viscous secretions affects the secretory epithelia and the respiratory condition usually leads to death. The relationship between the CFTR genotype and the disease phenotype is not well understood. Other risk factors such as genetic and autoimmune influence the development of this disease. We analyzed the PTPN22 R620W polymorphism (+1858 C/T, rs2476601) in 78 DNA samples from CF patients and 232 healthy controls from northeast Mexico using the polymerase chain reaction-restriction fragment length (PCR-RFLP) method. The C allele and the CC genotype were the most frequently detected in controls (CC genotype 96.12%; C allele 98.06%) compared with CF patients (CC genotype 88.46%, C allele 93.59%). A statistically significant association for the CT + TT genotypes (p = 0.012, OR = 3.232) as well as for the mutant T allele (p = 0.005, OR = 3.463) was found when comparing CF patients with controls. A significant association was found between the rs2476601 polymorphism of the PTPN22 gene and CF in Mexican patients. Further studies are necessary to understand the influence of this variant on lung neutrophil function and disease development.

Dopaminergic Modulation of Striatal Inhibitory Transmission and Long-Term Plasticity.

Dopamine (DA) modulates glutamatergic synaptic transmission and its plasticity in the striatum; however it is not well known how DA modulates long-term plasticity of striatal GABAergic inhibitory synapses. This work focused on the analysis of both dopaminergic modulation of inhibitory synapses and the synaptic plasticity established between GABAergic afferents to medium spiny neurons (MSNs). Our results showed that low and high DA concentrations mainly reduced the amplitude of inhibitory synaptic response; however detailed analysis of the D1 and D2 participation in this modulation displayed a wide variability in synaptic response. Analyzing DA participation in striatal GABAergic plasticity we observed that high frequency stimulation (HFS) of GABAergic interneurons in the presence of DA at a low concentration (200 nM) favored the expression of inhibitory striatal LTD, whereas higher concentration of DA (20 µM) primarily induced LTP. Interestingly, the plasticity induced in an animal model of striatal degeneration mimicked that induced in the presence of DA at a high concentration, which was not abolished with D2 antagonist but was prevented by PKA blocker.