Laparoscopic cholecystectomy in super elderly (> 90 years of age): safety and outcomes.

BACKGROUND: Nonagenarian patients are an age group in progressive growth. In this age group, indications for surgical procedures, including cholecystectomy, will be increasingly frequent, as biliary pathology and its complications are frequent in this population group. The main objective of this study was to analyze the safety and outcomes of laparoscopic cholecystectomy in patients older than 90 years. METHODS: A retrospective observational cohort study was designed. This study involved 600 patients that were classified in 4 age groups for analysis (under 50 years, 50-69 years, 70-89 years, and over 90 years). Demographic, clinical, paraclinics, surgical, and outcome variables were compared according to age group. A multivariate analysis, which included variables considered clinically relevant, was performed to identify factors associated with mortality and complications classified with the Clavien-Dindo scale. RESULTS: The patients evaluated had a median age of 65.0 (IQR 34.0) years and there was a female predominance (61.8%). A higher complication rate, conversion rate, subtotal cholecystectomy rate, and prolonged hospital stay were found in nonagenarians. The overall mortality rate was 1.6%. Mortality in the age group over 90 years was 6.8%. Regression models showed that age over 90 years (RR 4.6 CI95% 1.07-20.13), presence of cholecystitis (RR 8.2 CI95% 1.29-51.81), and time from admission to cholecystectomy (RR 1.2 CI95% 1.10-1.40) were the variables that presented statistically significant differences as risk factors for mortality. CONCLUSION: Cholecystectomy in nonagenarian patients has a higher rate of complications, conversion rate, subtotal cholecystectomy rate, and mortality. Therefore, an adequate perioperative assessment is necessary to optimize comorbidities and improve outcomes. Also, it is important to know the greatest risk for informed consent and choose the surgical equipment and schedule of the procedure.

Peltigera frigida Lichens and Their Substrates Reduce the Influence of Forest Cover Change on Phosphate Solubilizing Bacteria.

Phosphorus (P) is one of the most critical macronutrients in forest ecosystems. More than 70 years ago, some Chilean Patagonian temperate forests suffered wildfires and the subsequent afforestation with foreign tree species such as pines. Since soil P turnover is interlinked with the tree cover, this could influence soil P content and bioavailability. Next to soil microorganisms, which are key players in P transformation processes, a vital component of Patagonian temperate forest are lichens, which represent microbial hotspots for bacterial diversity. In the present study, we explored the impact of forest cover on the abundance of phosphate solubilizing bacteria (PSB) from three microenvironments of the forest floor: Peltigera frigida lichen thallus, their underlying substrates, and the forest soil without lichen cover. We expected that the abundance of PSB in the forest soil would be strongly affected by the tree cover composition since the aboveground vegetation influences the edaphic properties; but, as P. frigida has a specific bacterial community, lichens would mitigate this impact. Our study includes five sites representing a gradient in tree cover types, from a mature forest dominated by the native species Nothofagus pumilio, to native second-growth forests with a gradual increase in the presence of Pinus contorta in the last sites. In each site, we measured edaphic parameters, P fractions, and the bacterial potential to solubilize phosphate by quantifying five specific marker genes by qPCR. The results show higher soluble P, labile mineral P, and organic matter in the soils of the sites with a higher abundance of P. contorta, while most of the molecular markers were less abundant in the soils of these sites. Contrarily, the abundance of the molecular markers in lichens and substrates was less affected by the tree cover type. Therefore, the bacterial potential to solubilize phosphate is more affected by the edaphic factors and tree cover type in soils than in substrates and thalli of P. frigida lichens. Altogether, these results indicate that the microenvironments of lichens and their substrates could act as an environmental buffer reducing the influence of forest cover composition on bacteria involved in P turnover.

Ketamine-Treatment During Late Adolescence Impairs Inhibitory Synaptic Transmission in the Prefrontal Cortex and Working Memory in Adult Rats.

Schizophrenia (SZ) is associated with changes in the structure and function of several brain areas. Several findings suggest that these impairments are related to a dysfunction in γ-aminobutyric acid (GABA) neurotransmission in brain areas such as the medial prefrontal cortex (mPFC), the hippocampus (HPC) and the primary auditory cortex (A1); however, it is still unclear how the GABAergic system is disrupted in these brain areas. Here, we examined the effect of ketamine (Ket) administration during late adolescence in rats on inhibition in the mPFC-, ventral HPC (vHPC), and A1. We observe that Ket treatment reduced the expression of the calcium-binding protein parvalbumin (PV) and the GABA-producing enzyme glutamic acid decarboxylase 67 (GAD67) as well as decreased inhibitory synaptic efficacy in the mPFC. In addition, Ket-treated rats performed worse in executive tasks that depend on the integrity and proper functioning of the mPFC. Conversely, we do not find such changes in vHPC or A1. Together, our results provide strong experimental support for the hypothesis that during adolescence, the function of the mPFC is more susceptible than that of HPC or A1 to NMDAR hypofunction, showing apparent structure specificity. Thus, the impairment of inhibitory circuitry in mPFC could be a convergent primary site of SZ-like behavior during the adulthood.

Uso de fármacos coadyuvantes de los anestésicos locales en anestesia regional pediátrica para el manejo del dolor agudo postoperatorio / Use of coadjuvant drugs of local anesthetics in pediatric regional anesthesia for acute postoperative pain management

La anestesia regional pediátrica, ya sea los bloqueos neuroaxiales como periféricos, constituye actualmente un pilar fundamental en el manejo analgésico multimodal orientado a los periodos intra y postoperatorio; facilitando una recuperación postquirúrgica óptima y un alta precoz en niños. La inyección única de anestésicos locales en el bloqueo regional posee una duración limitada. Para conocer las técnicas y fármacos coadyuvantes de los anestésicos locales disponibles, destinados a prolongar la duración del bloqueo en inyección única, hemos efectuado una revisión del uso de fármacos coadyuvantes de los anestésicos locales utilizados, describiendo los mecanismos de acción, la evidencia clínica de sus beneficios; como también, la incidencia de complicaciones y los riesgos asociados a su uso.

Pediatric regional anesthesia, whether neuro axial or peripheral nerve blocks, is currently a base in multimodal analgesic management aimed at the intra and postoperative periods; enabling optimal postoperative recovery and early discharge in children. Single injection of local anesthetics in regional blockade has a limited duration. In order to know the techniques and adjuvant drugs of the available local anesthetics, designed to prolong the duration of block in single injection, we have reviewed the use of adjuvants, describing the mechanisms of action, the clinical evidence of their benefits; as well as, the incidence of complications and the risks associated with its use.

Innate Sensing of the Gut Microbiota: Modulation of Inflammatory and Autoimmune Diseases.

The mammalian gastrointestinal tract harbors a diverse microbial community with which dynamic interactions have been established over millennia of coevolution. Commensal bacteria and their products are sensed by innate receptors expressed in gut epithelia and in gut-associated immune cells, thereby promoting the proper development of mucosal immune system and host homeostasis. Many studies have demonstrated that host-microbiota interactions play a key role during local and systemic immunity. Therefore, this review will focus on how innate sensing of the gut microbiota and their metabolites through inflammasome and toll-like receptors impact the modulation of a distinct set of inflammatory and autoimmune diseases. We believe that a better understanding of the fine-tuning that governs host-microbiota interactions will further improve common prophylactic and therapeutic applications.

Clinical significance of tumor expression of major histocompatibility complex class I-related chains A and B (MICA/B) in gastric cancer patients.

Gastric cancer (GC) is the third most common cause of cancer death worldwide. Natural killer cells play an important role in the immune defense against transformed cells. They express the activating receptor NKG2D, whose ligands belong to the MIC and ULBP/RAET family. Although it is well established that these ligands are generally expressed in tumors, the association between their expression in the tumor and gastric mucosa and clinical parameters and prognosis of GC remains to be addressed. In the present study, MICA and MICB expression was analyzed, by flow cytometry, in 23 and 20 pairs of gastric tumor and adjacent non-neoplasic gastric mucosa, respectively. Additionally, ligands expression in 13 tumors and 7 gastric mucosa samples from GC patients were evaluated by immunohistochemistry. The mRNA levels of MICA in 9 pairs of tumor and mucosa were determined by quantitative PCR. Data were associated with the clinicopathological characteristics and the patient outcome. MICA expression was observed in 57% of tumors (13/23) and 44% of mucosal samples (10/23), while MICB was detected in 50% of tumors (10/20) and 45% of mucosal tissues (9/20). At the protein level, ligand expression was significantly higher in the tumor than in the gastric mucosa. MICA mRNA levels were also increased in the tumor as compared to the mucosa. However, clinicopathological analysis indicated that, in patients with tumors >5 cm, the expression of MICA and MICB in the tumor did not differ from that of the mucosa, and tumors >5 cm showed significantly higher MICA and MICB expression than tumors ≤5 cm. Patients presenting tumors >5 cm that expressed MICA and MICB had substantially shorter survival than those with large tumors that did not express these ligands. Our results suggest that locally sustained expression of MICA and MICB in the tumor may contribute to the malignant progression of GC and that expression of these ligands predicts an unfavorable prognosis in GC patients presenting large tumors.

Dialectical Behavior Therapy for Suicidal Latina Adolescents: Supplemental Dialectical Corollaries and Treatment Targets.

The primary aim of this paper is to describe extreme behavioral patterns that the authors have observed in treating Latina adolescents who are suicidal and their parents within the framework of dialectical behavior therapy (DBT). These extreme patterns, called dialectical corollaries, serve to supplement the adolescent/family dialectical dilemmas described by Rathus and Miller (2002) as part of dialectical behavior therapy for suicidal adolescents with borderline personality features. The dialectical corollaries proposed are "old school versus new school" and "overprotecting" versus "underprotecting," and they are described in-depth. We also identify specific treatment targets for each corollary and discuss therapeutic techniques aimed at achieving a synthesis between the polarities that characterize each corollary. Lastly, we suggest clinical strategies to use when therapists reach a therapeutic impasse with the parent-adolescent dyad (i.e., dialectical failures).

Extracellular α-synuclein alters synaptic transmission in brain neurons by perforating the neuronal plasma membrane.

It has been postulated that the accumulation of extracellular α-synuclein (α-syn) might alter the neuronal membrane by formation of 'pore-like structures' that will lead to alterations in ionic homeostasis. However, this has never been demonstrated to occur in brain neuronal plasma membranes. In this study, we show that α-syn oligomers rapidly associate with hippocampal membranes in a punctate fashion, resulting in increased membrane conductance (5 fold over control) and the influx of both calcium and a fluorescent glucose analogue. The enhancement in intracellular calcium (1.7 fold over control) caused a large increase in the frequency of synaptic transmission (2.5 fold over control), calcium transients (3 fold over control), and synaptic vesicle release. Both primary hippocampal and dissociated nigral neurons showed rapid increases in membrane conductance by α-syn oligomers. In addition, we show here that α-syn caused synaptotoxic failure associated with a decrease in SV2, a membrane protein of synaptic vesicles associated with neurotransmitter release. In conclusion, extracellular α-syn oligomers facilitate the perforation of the neuronal plasma membrane, thus explaining, in part, the synaptotoxicity observed in neurodegenerative diseases characterized by its extracellular accumulation. We propose that α-synuclein (α-syn) oligomers form pore-like structures in the plasma membrane of neurons from central nervous system (CNS). We believe that extracellular α-syn oligomers facilitate the formation of α-syn membrane pore-like structures, thus explaining, in part, the synaptotoxicity observed in neurodegenerative diseases characterized by its extracellular accumulation. We think that alterations in ionic homeostasis and synaptic vesicular depletion are key steps that lead to synaptotoxicity promoted by α -syn membrane pore-like structures.

Daam1a mediates asymmetric habenular morphogenesis by regulating dendritic and axonal outgrowth.

Although progress has been made in resolving the genetic pathways that specify neuronal asymmetries in the brain, little is known about genes that mediate the development of structural asymmetries between neurons on left and right. In this study, we identify daam1a as an asymmetric component of the signalling pathways leading to asymmetric morphogenesis of the habenulae in zebrafish. Daam1a is a member of the Formin family of actin-binding proteins and the extent of Daam1a expression in habenular neuron dendrites mirrors the asymmetric growth of habenular neuropil between left and right. Local loss and gain of Daam1a function affects neither cell number nor subtype organisation but leads to a decrease or increase of neuropil, respectively. Daam1a therefore plays a key role in the asymmetric growth of habenular neuropil downstream of the pathways that specify asymmetric cellular domains in the habenulae. In addition, Daam1a mediates the development of habenular efferent connectivity as local loss and gain of Daam1a function impairs or enhances, respectively, the growth of habenular neuron terminals in the interpeduncular nucleus. Abrogation of Daam1a disrupts the growth of both dendritic and axonal processes and results in disorganised filamentous actin and α-tubulin. Our results indicate that Daam1a plays a key role in asymmetric habenular morphogenesis mediating the growth of dendritic and axonal processes in dorsal habenular neurons.