Neuronal inputs and outputs of aging and longevity.

An animal's survival strongly depends on its ability to maintain homeostasis in response to the changing quality of its external and internal environment. This is achieved through intracellular and intercellular communication within and among different tissues. One of the organ systems that plays a major role in this communication and the maintenance of homeostasis is the nervous system. Here we highlight different aspects of the neuronal inputs and outputs of pathways that affect aging and longevity. Accordingly, we discuss how sensory inputs influence homeostasis and lifespan through the modulation of different types of neuronal signals, which reflects the complexity of the environmental cues that affect physiology. We also describe feedback, compensatory, and feed-forward mechanisms in these longevity-modulating pathways that are necessary for homeostasis. Finally, we consider the temporal requirements for these neuronal processes and the potential role of natural genetic variation in shaping the neurobiology of aging

Socioeconomic and demographic factors associated with failure in Helicobacter pylori eradication using the standard triple therapy

Aim: To evaluate the influence of socioeconomic and demographic factors on the eradication rate of H. pylori, using standard triple therapy Background: the efficacy of the standard triple therapy (STT) for H. pylori eradication has decreased with the rise of antibiotic resistance. Other factors could influence the eradication failure, although available results are conflicting. Methods: Retrospective study, including adults with H. pylori infection treated de novo with STT (proton pump inhibitor, amoxicillin and clarithromycin). Eradication success was assessed by 13C-urea breath test. Demographic and socioeconomics variables were evaluated and correlated with eradication treatment outcome. The confounder variables were controlled by logistic regression analysis. Results: Out of 902 patients with H. pylori diagnosis, 693 met inclusion criteria (average age 53 years; females 55.2%). Nonsignificant differences were observed in relation to economics income between rural and urban areas (p=0.316). The eradication rate of H. pylori was 71.1%: male 78.9% vs female 65.9%, urban area 73.4% vs rural area 64.1%. With reference to age, income and nationality, the eradication rates were similar in all groups. According to logistic regression analysis, females had almost twice more likelihood of eradication failure in relation to males (OR 1.92; 95%CI: 1.38-2.72); and rural residents had OR 1.55 (95%CI: 1.03- 2.33) for having eradication failure in contrast with urban population. Conclusion: Female gender and rural residence are factors associated with H. Pylori eradication failure with standard triple therapy

Simbiótico conteniendo bacillus coagulans LMG-S-24828 y prebióticos en la reducción de trastornos gastrointestinales secundarios al tratamiento farmacológico de enfermedades hematológicas crónicas. Estudio piloto

Poster [PC-353] Introducción: Algunos fármacos inhibidores de Tirosin-kinasa (ITK) utilizados en el tratamiento de la leucemia mieloide crónica, y Miglustat, un iminoazúcar empleado en enfermedades lisosomales, pueden producir trastornos gastrointestinales como diarrea, meteorismo y dolor abdominal. Estos efectos adversos disminuyen la calidad de vida relacionada con la salud y provocan abandonos del tratamiento. Algunos probióticos han demostrado mejoría de los síntomas mencionados en pacientes con trastornos funcionales digestivos. Hipótesis: El simbiótico conteniendo Bacillus coagulans LMG-S-24828 y prebióticos reduce los efectos adversos gastrointestinales asociados a la utilización de ITKs y Miglustat y mejora la adherencia al tratamiento. Objetivos: Evaluar el efecto de la administración controlada de dicho simbiótico durante un mes, sobre la calidad de vida relacionada con la salud gastrointestinal en pacientes tratados con ITKs y miglustat. Secundariamente, establecer si el simbiótico aporta ventajas en la adherencia a los tratamientos citados. Métodos: Ensayo clínico aleatorizado de diseño cruzado en el que a 9 pacientes en tratamiento con ITKs o Miglustat se les administró de forma ciega placebo o simbiótico en una dosis diaria, con una fase de “lavado” de dos meses entre la administración de cada uno. Se solicitó al paciente cumplimentar la versión validada en español del cuestionario de Calidad de Vida Gastrointestinal GIQLI (Gastrointestinal Quality of Life Index) antes de la primera dosis de cada producto y trascurrido un mes desde su inicio. Se evaluó la frecuencia de abandono del tratamiento en cada grupo. El análisis de los resultados se realizó por protocolo mediante el test no paramétrico de Mann-Whitney, considerando significación estadística las diferencias con p valor<0, 05. El protocolo fue aprobado por el Comité de Ética autonómico. Resultados: Inicialmente se reclutaron 11 pacientes procedentes de un único centro, de los que 9 (5 H/ 4M), edad media: 49 (29-79) finalizaron el estudio. Tras un mes en tratamiento con simbiótico observamos una diferencia estadísticamente significativa (p=0, 039) en la puntuación media del cuestionario GIQLI no alcanzada con placebo. Ningún paciente abandonó el tratamiento con ITKs/Miglustat, ni se observaron variaciones analíticas en los biomarcadores de la enfermedad. Conclusiones: En pacientes bajo tratamiento con ITKs o Miglustat el simbiótico mejoró significativamente los síntomas adversos gastrointestinales. Este beneficio no fue observado con placebo y no se relacionó con el grado de adherencia terapéutica

Un simbiótico conteniendo bacillus coagulans LMG-S-24828 reduce los síntomas gastrointestinales secundarios al tratamiento farmacológico de enfermedades hematológicas crónicas. Estudio multicéntrico

PB-062 Introducción: La presencia de blastos permite diagnosticar, en muchas ocasiones, una neoplasia hematológica dentro de un amplio abanico de posibilidades diagnósticas, siendo el ejemplo clásico el de las leucemias agudas. Además, apoyando al examen morfológico, la citometría de flujo es de gran utilidad para el diagnóstico y la clasificación de estas neoplasias. Existen otras enfermedades no neoplásicas que se manifiestan con células inmaduras, por ello presentamos el caso de una lactante de 19 meses con hepatoesplenomegalia, presencia de blastos con diagnóstico inicial de leucemia aguda que no se confirma tras un estudio completo. Métodos y Resultados: Presentamos una lactante de 19 meses que acude por fiebre de 15 días de predominio nocturno, máximo 39,5ºC, distensión abdominal y desde dos semanas antes de ingreso coincidiendo con reinicio de fiebre, mayor aumento del perímetro abdominal. Se realiza ecografía abdominal con esplenomegalia de 10,7 cm, bazo accesorio de 1,6x1,5 cm. A la exploración se objetiva palidez cutánea, abdomen distendido, no doloroso y marcada hepatoesplenomegalia. ..

Functional divergence in the role of N-linked glycosylation in smoothened signaling

The G protein-coupled receptor (GPCR) Smoothened (Smo) is the requisite signal transducer of the evolutionarily conserved Hedgehog (Hh) pathway. Although aspects of Smo signaling are conserved from Drosophila to vertebrates, significant differences have evolved. These include changes in its active sub-cellular localization, and the ability of vertebrate Smo to induce distinct G protein-dependent and independent signals in response to ligand. Whereas the canonical Smo signal to Gli transcriptional effectors occurs in a G protein-independent manner, its non-canonical signal employs Gαi. Whether vertebrate Smo can selectively bias its signal between these routes is not yet known. N-linked glycosylation is a post-translational modification that can influence GPCR trafficking, ligand responsiveness and signal output. Smo proteins in Drosophila and vertebrate systems harbor N-linked glycans, but their role in Smo signaling has not been established. Herein, we present a comprehensive analysis of Drosophila and murine Smo glycosylation that supports a functional divergence in the contribution of N-linked glycans to signaling. Of the seven predicted glycan acceptor sites in Drosophila Smo, one is essential. Loss of N-glycosylation at this site disrupted Smo trafficking and attenuated its signaling capability. In stark contrast, we found that all four predicted N-glycosylation sites on murine Smo were dispensable for proper trafficking, agonist binding and canonical signal induction. However, the under-glycosylated protein was compromised in its ability to induce a non-canonical signal through Gαi, providing for the first time evidence that Smo can bias its signal and that a post-translational modification can impact this process. As such, we postulate a profound shift in N-glycan function from affecting Smo ER exit in flies to influencing its signal output in mice

Evaluation of a New Monoclonal Chemiluminescent Immunoassay Stool Antigen Test for the Diagnosis of Helicobacter pylori Infection: A Spanish Multicentre Study

The stool antigen test (SAT) represents an attractive alternative for detection of Helicobacter pylori. The aim of this study was to assess the accuracy of a new SAT, the automated LIAISON(R) Meridian H. pylori SA based on monoclonal antibodies, compared to the defined gold standard C-13-urea breath test (UBT). This prospective multicentre study (nine Spanish centres) enrolled patients >= 18 years of age with clinical indication to perform UBT for the initial diagnosis and for confirmation of bacterial eradication. Two UBT methods were used: mass spectrometry (MS) including citric acid (CA) or infrared spectrophotometry (IRS) without CA. Overall, 307 patients (145 naive, 162 with confirmation of eradication) were analysed. Using recommended cut-off values (negative SAT = 1.10) the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 67%, 97%, 86%, 92% and 91%, respectively, obtaining an area under the receiver operating characteristic (ROC) curve (AUC) of 0.85. Twenty-eight patients, including seven false positives and 21 false negatives, presented a discordant result between SAT and UBT. Among the 21 false negatives, four of six tested with MS and 11 of 15 tested with IRS presented a borderline UBT delta value. In 25 discordant samples, PCR targeting H. pylori DNA was performed to re-assess positivity and SAT accuracy was re-analysed: sensitivity, specificity, positive predictive value, negative predictive value, accuracy and AUC were 94%, 97%, 86%, 99%, 97% and 0.96, respectively. The new LIAISON(R) Meridian H. pylori SA SAT showed a good accuracy for diagnosis of H. pylori infection

Naming a phantom – the quest to find the identity of Ulluchu, an unidentified ceremonial plant of the Moche culture in Northern Peru

The botanical identification of Ulluchu, an iconic fruit frequently depicted in the art of the pre-Columbian Moche culture that flourished from A.D. 100–800 on the Peruvian north coast, has eluded scientists since its documentation in ceramics in the 1930s. Moche fine-line drawings of Ulluchu normally depict seed-pods or seeds floating in the air in sacrificial scenes, associated with runners and messengers or intoxicated priests. It is a grooved, comma-shaped fruit with an enlarged calyx found mainly in fine-line scenes painted on Moche ceramics. The term first appeared without linguistic explanation in the work of pioneer Moche scholar Rafael Larco Hoyle, and the identification of the plant was seen as the largest remaining challenge in current archaebotany at the Peruvian North coast. The name Ulluchu seems to have been coined by Larco. According to his description, the name originated in the Virú River valley, and is supposedly of Mochica origin. However, there is no linguistic evidence that such a term indeed existed in the Mochica or Yunga language

European registry on helicobacter pylori management: Effectiveness of first and second-line treatment in Spain

The management of Helicobacter pylori infection has to rely on previous local effectiveness due to the geographical variability of antibiotic resistance. The aim of this study was to evaluate the effectiveness of first and second-line H. pylori treatment in Spain, where the empirical prescription is recommended. A multicentre prospective non-interventional registry of the clinical practice of European gastroenterologists concerning H. pylori infection (Hp-EuReg) was developed, including patients from 2013 until June 2019. Effectiveness was evaluated descriptively and through a multivariate analysis concerning age, gender, presence of ulcer, proton-pump in-hibitor (PPI) dose, therapy duration and compliance. Overall, 53 Spanish hospitals were included, and 10, 267 patients received a first-line therapy. The best results were obtained with the 10-day bismuth single-capsule therapy (95% cure rate by intention-to-treat) and with both the 14-day bismuth-clarithromycin quadruple (PPI-bismuth-clarithromycin-amoxicillin, 91%) and the 14-day non-bismuth quadruple concomitant (PPI-clarithromycin-amoxicillin-metronidazole, 92%) therapies. Second-line therapies were prescribed to 2448 patients, with most-effective therapies being the triple quinolone (PPI-amoxicillin-levofloxacin/moxifloxacin) and the bismuth-levofloxacin quadruple schemes (PPI-bismuth-levofloxacin-amoxicillin) prescribed for 14 days (92%, 89% and 90% effective-ness, respectively), and the bismuth single-capsule (10 days, 88.5%). Compliance, longer duration and higher acid inhibition were associated with higher effectiveness. “Optimized” H. pylori therapies achieve over 90% success in Spain

Human PTCHD3 nulls: rare copy number and sequence variants suggest a non-essential gene

<p>Abstract</p> <p>Background</p> <p>Copy number variations (CNVs) can contribute to variable degrees of fitness and/or disease predisposition. Recent studies show that at least 1% of any given genome is copy number variable when compared to the human reference sequence assembly. Homozygous deletions (or CNV nulls) that are found in the normal population are of particular interest because they may serve to define non-essential genes in human biology.</p> <p>Results</p> <p>In a genomic screen investigating CNV in Autism Spectrum Disorders (ASDs) we detected a heterozygous deletion on chromosome 10p12.1, spanning the Patched-domain containing 3 (<it>PTCHD3</it>) gene, at a frequency of ~1.4% (6/427). This finding seemed interesting, given recent discoveries on the role of another Patched-domain containing gene (<it>PTCHD1</it>) in ASD. Screening of another 177 ASD probands yielded two additional heterozygous deletions bringing the frequency to 1.3% (8/604). The deletion was found at a frequency of ~0.73% (27/3,695) in combined control population from North America and Northern Europe predominately of European ancestry. Screening of the human genome diversity panel (HGDP-CEPH) covering worldwide populations yielded deletions in 7/1,043 unrelated individuals and those detected were confined to individuals of European/Mediterranean/Middle Eastern ancestry. Breakpoint mapping yielded an identical 102,624 bp deletion in all cases and controls tested, suggesting a common ancestral event. Interestingly, this CNV occurs at a break of synteny between humans and mouse. Considering all data, however, no significant association of these rare <it>PTCHD3 </it>deletions with ASD was observed. Notwithstanding, our RNA expression studies detected <it>PTCHD3 </it>in several tissues, and a novel shorter isoform for <it>PTCHD3 </it>was characterized. Expression in transfected COS-7 cells showed <it>PTCHD3 </it>isoforms colocalize with calnexin in the endoplasmic reticulum. The presence of a patched (Ptc) domain suggested a role for <it>PTCHD3 </it>in various biological processes mediated through the Hedgehog (Hh) signaling pathway. However, further investigation yielded one individual harboring a homozygous deletion (<it>PTCHD3 </it>null) without ASD or any other overt abnormal phenotype. Exon sequencing of <it>PTCHD3 </it>in other individuals with deletions revealed compound point mutations also resulting in a null state.</p> <p>Conclusion</p> <p>Our data suggests that <it>PTCHD3 </it>may be a non-essential gene in some humans and characterization of this novel CNV at 10p12.1 will facilitate population and disease studies.</p

A Neuromedin U Receptor Acts with the Sensory System to Modulate Food Type-Dependent Effects on C. elegans Lifespan

Different food types modulate worm lifespan and involve the neuropeptide receptor NMUR-1, which acts with the sensory neurons in a bacterial lipopolysaccaharide structure-dependent manner