Use of Caudal Quadratus Lumborum Block with Ropivacaine as Part of an Opioid-Free Analgesic Protocol in Dogs Undergoing Orchiectomy: A Randomized Trial.

In veterinary medicine, the use of loco-regional anesthesia techniques is increasing. The Quadratus Lumborum block (QL) is an interfascial loco-regional technique that involves the release of local anesthetic (LA) between the Quadratus Lumborum and the Small Psoas (Pm) muscle. The study aims to evaluate the effect of the QL block on reducing the total amount of opioids in dogs undergoing pre-scrotal orchiectomy. A group of 36 dogs was enrolled in a randomized blinded study. The animals were divided into two groups: 18 in the experimental group (QL) and 18 in the control group (C). The QL group received 0.4 mL kg-1 of ropivacaine 0.5% for each hemiabdomen (total amount of 3 mg kg-1 of ropivacaine, 1.5 mg kg-1 per side). The C group was brought into the operating room (OR) after receiving the same clipping as the QL group. In the intraoperative period, opioid consumption in the QL group was significantly lower than in the C group. No differences were found in the post-operative phase. No side effects were reported when performing the QL technique. The QL block performed at the level of L6 appears to be a valid approach to reducing opioid use in dogs undergoing orchidectomy with a pre-scrotal surgical approach.

Revitalizing agriculture: next-generation genotyping and -omics technologies enabling molecular prediction of resilient traits in the Solanaceae family.

This review highlights -omics research in Solanaceae family, with a particular focus on resilient traits. Extensive research has enriched our understanding of Solanaceae genomics and genetics, with historical varietal development mainly focusing on disease resistance and cultivar improvement but shifting the emphasis towards unveiling resilience mechanisms in genebank-preserved germplasm is nowadays crucial. Collecting such information, might help researchers and breeders developing new experimental design, providing an overview of the state of the art of the most advanced approaches for the identification of the genetic elements laying behind resilience. Building this starting point, we aim at providing a useful tool for tackling the global agricultural resilience goals in these crops.

Boosting grapevine breeding for climate-smart viticulture: from genetic resources to predictive genomics.

The multifaceted nature of climate change is increasing the urgency to select resilient grapevine varieties, or generate new, fitter cultivars, to withstand a multitude of new challenging conditions. The attainment of this goal is hindered by the limiting pace of traditional breeding approaches, which require decades to result in new selections. On the other hand, marker-assisted breeding has proved useful when it comes to traits governed by one or few genes with great effects on the phenotype, but its efficacy is still restricted for complex traits controlled by many loci. On these premises, innovative strategies are emerging which could help guide selection, taking advantage of the genetic diversity within the Vitis genus in its entirety. Multiple germplasm collections are also available as a source of genetic material for the introgression of alleles of interest via adapted and pioneering transformation protocols, which present themselves as promising tools for future applications on a notably recalcitrant species such as grapevine. Genome editing intersects both these strategies, not only by being an alternative to obtain focused changes in a relatively rapid way, but also by supporting a fine-tuning of new genotypes developed with other methods. A review on the state of the art concerning the available genetic resources and the possibilities of use of innovative techniques in aid of selection is presented here to support the production of climate-smart grapevine genotypes.

Increased KV2.1 Channel Clustering Underlies the Reduction of Delayed Rectifier K+ Currents in Hippocampal Neurons of the Tg2576 Alzheimer's Disease Mouse.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive deterioration of cognitive functions. Cortical and hippocampal hyperexcitability intervenes in the pathological derangement of brain activity leading to cognitive decline. As key regulators of neuronal excitability, the voltage-gated K+ channels (KV) might play a crucial role in the AD pathophysiology. Among them, the KV2.1 channel, the main α subunit mediating the delayed rectifier K+ currents (IDR) and controlling the intrinsic excitability of pyramidal neurons, has been poorly examined in AD. In the present study, we investigated the KV2.1 protein expression and activity in hippocampal neurons from the Tg2576 mouse, a widely used transgenic model of AD. To this aim we performed whole-cell patch-clamp recordings, Western blotting, and immunofluorescence analyses. Our Western blotting results reveal that KV2.1 was overexpressed in the hippocampus of 3-month-old Tg2576 mice and in primary hippocampal neurons from Tg2576 mouse embryos compared with the WT counterparts. Electrophysiological experiments unveiled that the whole IDR were reduced in the Tg2576 primary neurons compared with the WT neurons, and that this reduction was due to the loss of the KV2.1 current component. Moreover, we found that the reduction of the KV2.1-mediated currents was due to increased channel clustering, and that glutamate, a stimulus inducing KV2.1 declustering, was able to restore the IDR to levels comparable to those of the WT neurons. These findings add new information about the dysregulation of ionic homeostasis in the Tg2576 AD mouse model and identify KV2.1 as a possible player in the AD-related alterations of neuronal excitability.

Insight into Carbohydrate Metabolism and Signaling in Grapevine Buds during Dormancy Progression.

Perennial fruit crops enter dormancy to ensure bud tissue survival during winter. However, a faster phenological advancement caused by global warming exposes bud tissue to a higher risk of spring frost damage. Tissue dehydration and soluble sugars accumulation are connected to freezing tolerance, but non-structural carbohydrates also act as metabolic substrates and signaling molecules. A deepened understanding of sugar metabolism in the context of winter freezing resistance is required to gain insight into adaptive possibilities to cope with climate changes. In this study, the soluble sugar content was measured in a cold-tolerant grapevine hybrid throughout the winter season. Moreover, the expression of drought-responsive hexose transporters VvHT1 and VvHT5, raffinose synthase VvRS and grapevine ABA-, Stress- and Ripening protein VvMSA was analyzed. The general increase in sugars in December and January suggests that they can participate in protecting bud tissues against low temperatures. The modulation of VvHT5, VvINV and VvRS appeared consistent with the availability of the different sugar species; challenging results were obtained for VvHT1 and VvMSA, suggesting interesting hypotheses about their role in the sugar-hormone crosstalk. The multifaceted role of sugars on the intricate phenomenon, which is the response of dormant buds to changing temperature, is discussed.

Na+/Ca2+ exchanger isoform 1 takes part to the Ca2+-related prosurvival pathway of SOD1 in primary motor neurons exposed to beta-methylamino-L-alanine.

BACKGROUND: The cycad neurotoxin beta-methylamino-L-alanine (L-BMAA), one of the environmental trigger factor for amyotrophic lateral sclerosis/Parkinson-dementia complex (ALS/PDC), may cause neurodegeneration by disrupting organellar Ca2+ homeostasis. Through the activation of Akt/ERK1/2 pathway, the Cu,Zn-superoxide dismutase (SOD1) and its non-metallated form, ApoSOD1, prevent endoplasmic reticulum (ER) stress-induced cell death in motor neurons exposed to L-BMAA. This occurs through the rapid increase of intracellular Ca2+ concentration ([Ca2+]i) in part flowing from the extracellular compartment and in part released from ER. However, the molecular components of this mechanism remain uncharacterized. METHODS: By an integrated approach consisting on the use of siRNA strategy, Western blotting, confocal double- labeling immunofluorescence, patch-clamp electrophysiology, and Fura 2-/SBFI-single-cell imaging, we explored in rat motor neuron-enriched cultures the involvement of the plasma membrane proteins Na+/Ca2+ exchanger (NCX) and purinergic P2X7 receptor as well as that of the intracellular cADP-ribose (cADPR) pathway, in the neuroprotective mechanism of SOD1. RESULTS: We showed that SOD1-induced [Ca2+]i rise was prevented neither by A430879, a P2X7 receptor specific antagonist or 8-bromo-cADPR, a cell permeant antagonist of cADP-ribose, but only by the pan inhibitor of NCX, CB-DMB. The same occurred for the ApoSOD1. Confocal double labeling immunofluorescence showed a huge expression of plasmalemmal NCX1 and intracellular NCX3 isoforms. Furthermore, we identified NCX1 reverse mode as the main mechanism responsible for the neuroprotective ER Ca2+ refilling elicited by SOD1 and ApoSOD1 through which they promoted translocation of active Akt in the nuclei of a subset of primary motor neurons. Finally, the activation of NCX1 by the specific agonist CN-PYB2 protected motor neurons from L-BMAA-induced cell death, mimicking the effect of SOD1. CONCLUSION: Collectively, our data indicate that SOD1 and ApoSOD1 exert their neuroprotective effect by modulating ER Ca2+ content through the activation of NCX1 reverse mode and Akt nuclear translocation in a subset of primary motor neurons. Video Abstract.

Tracheal intubation while wearing personal protective equipment in simulation studies: a systematic review and meta-analysis with trial-sequential analysis.

BACKGROUND: Tracheal intubation in patients with coronavirus disease-19 is a high-risk procedure that should be performed with personal protective equipment (PPE). The influence of PPE on operator's performance during tracheal intubation remains unclear. METHODS: We conducted a systematic review and meta-analysis of simulation studies to evaluate the influence of wearing PPE as compared to standard uniform regarding time-to-intubation (TTI) and success rate. Subgroup analyses were conducted according to device used and operator's experience. RESULTS: The TTI was prolonged when wearing PPE (eight studies): Standard Mean Difference (SMD) -0.54, 95% Confidence Interval [-0.75, -0.34], p <  0.0001. Subgroup analyses according to device used showed similar findings (direct laryngoscopy, SMD -0.63 [-0.88, -0.38], p < 0.0001; videolaryngoscopy, SMD -0.39 [-0.75, -0.02], p =  0.04). Considering the operator's experience, non-anesthesiologists had prolonged TTI (SMD -0.75 [-0.98, -0.52], p < 0.0001) while the analysis on anesthesiologists did not show significant differences (SMD -0.25 [-0.51, 0.01], p = 0.06). The success rate of tracheal intubation was not influenced by PPE: Risk Ratio (RR) 1.02 [1.00, 1.04]; p = 0.12). Subgroup analyses according to device demonstrated similar results (direct laryngoscopy, RR 1.03 [0.99, 1.07], p = 0.15, videolaryngoscopy, RR 1.01 [0.98, 1.04], p =  0.52). Wearing PPE had a trend towards negative influence on success rate in non-anesthesiologists (RR 1.05 [1.00, 1.10], p = 0.05), but not in anesthesiologists (RR 1.00 [0.98, 1.03], p = 0.84). Trial-sequential analyses for TTI and success rate indicated robustness of both results. CONCLUSIONS: Under simulated conditions, wearing PPE delays the TTI as compared to dressing standard uniform, with no influence on the success rate. However, certainty of evidence is very low. Performing tracheal intubation with direct laryngoscopy seems influenced to a greater extent as compared to videolaryngoscopy. Similarly, wearing PPE affects more the non-anesthesiologists subgroup as compared to anesthesiologists.

The Na+/Ca2+ Exchanger 3 Is Functionally Coupled With the NaV1.6 Voltage-Gated Channel and Promotes an Endoplasmic Reticulum Ca2+ Refilling in a Transgenic Model of Alzheimer's Disease.

The remodelling of neuronal ionic homeostasis by altered channels and transporters is a critical feature of the Alzheimer's disease (AD) pathogenesis. Different reports converge on the concept that the Na+/Ca2+ exchanger (NCX), as one of the main regulators of Na+ and Ca2+ concentrations and signalling, could exert a neuroprotective role in AD. The activity of NCX has been found to be increased in AD brains, where it seemed to correlate with an increased neuronal survival. Moreover, the enhancement of the NCX3 currents (INCX) in primary neurons treated with the neurotoxic amyloid ß 1-42 (Aß1-42) oligomers prevented the endoplasmic reticulum (ER) stress and neuronal death. The present study has been designed to investigate any possible modulation of the INCX, the functional interaction between NCX and the NaV1.6 channel, and their impact on the Ca2+ homeostasis in a transgenic in vitro model of AD, the primary hippocampal neurons from the Tg2576 mouse, which overproduce the Aß1-42 peptide. Electrophysiological studies, carried in the presence of siRNA and the isoform-selective NCX inhibitor KB-R7943, showed that the activity of a specific NCX isoform, NCX3, was upregulated in its reverse, Ca2+ influx mode of operation in the Tg2576 neurons. The enhanced NCX activity contributed, in turn, to increase the ER Ca2+ content, without affecting the cytosolic Ca2+ concentrations of the Tg2576 neurons. Interestingly, our experiments have also uncovered a functional coupling between NCX3 and the voltage-gated NaV1.6 channels. In particular, the increased NaV1.6 currents appeared to be responsible for the upregulation of the reverse mode of NCX3, since both TTX and the Streptomyces griseolus antibiotic anisomycin, by reducing the NaV1.6 currents, counteracted the increase of the INCX in the Tg2576 neurons. In agreement, our immunofluorescence analyses revealed that the NCX3/NaV1.6 co-expression was increased in the Tg2576 hippocampal neurons in comparison with the WT neurons. Collectively, these findings indicate that NCX3 might intervene in the Ca2+ remodelling occurring in the Tg2576 primary neurons thus emerging as a molecular target with a neuroprotective potential, and provide a new outcome of the NaV1.6 upregulation related to the modulation of the intracellular Ca2+ concentrations in AD neurons.

Continuous Erector Spinae Plane Block as Postoperative Analgesic Technique for Robotic-Assisted Thoracic Surgery: A Case Series.

INTRODUCTION: The erector spinae plane block (ESPB) is a recently implemented analgesic technique initially reported for thoracic analgesia and subsequently adopted for both intra- and postoperative pain management. Thoracic surgery is among the most painful surgical procedures, even when conducted with minimally invasive approach. Robotic-assisted thoracic surgery (RATS) challenges the traditional analgesic regimens as one of its aims is to decrease the patient's length of stay (LOS) whilst achieving optimal postoperative pain management. Furthermore, there is lots of growing evidence on the impact of poorly controlled postoperative pain (PP) on the development of chronic post-surgical pain (CPSP). In these case series, we aim to describe our preliminary experience of postoperative pain management with continuous ESPB in the field of RATS. CASE SERIES PRESENTATION: In eight consecutive patients undergoing elective RATS procedure, we performed the ESPB after surgery with an initial bolus of local anesthetic followed by catheter insertion for continuous infusion. The infusion of local anesthetic lasted for the first two postoperative days. The effectiveness of the ESPB was evaluated through serial pain assessment with numeric rate scale (NRS) score, both at rest and during movement every 6 hours. Any analgesic rescue drug prescription was reported. We noted that the ESPB strongly reduced the prescription of opioids and of rescue analgesic. In our series, only one patient needed opioids during the first two postoperative days, and no rescue analgesic administration was noted in the remaining cases. CONCLUSION: We report a small but promising experience regarding postoperative pain management with continuous ESPB performed after RATS. We implemented the ESPB before surgery. Larger studies on postoperative pain management with continuous regional blocks in thoracic surgery are warranted.

Neurofibromatosis and HIV infection in a pregnant woman.

Although pregnant neurofibromatosis or HIV patient established a high-risk group, this report demonstrated that a careful planning and widespread valuations should be associated with a favorable prognosis for both mother and newborn.

Rebound effects of NCX3 pharmacological inhibition: A novel strategy to accelerate myelin formation in oligodendrocytes.

The Na+/Ca2+ exchanger NCX3 is an important regulator of sodium and calcium homeostasis in oligodendrocyte lineage. To date, no information is available on the effects resulting from prolonged exposure to NCX3 blockers and subsequent drug washout in oligodendroglia. Here, we investigated, by means of biochemical, morphological and functional analyses, the pharmacological effects of the NCX3 inhibitor, the 5-amino-N-butyl-2-(4-ethoxyphenoxy)-benzamide hydrochloride (BED), on NCXs expression and activity, as well as intracellular [Na+]i and [Ca2+]i levels, during treatment and following drug washout both in human MO3.13 oligodendrocytes and rat primary oligodendrocyte precursor cells (OPCs). BED exposure antagonized NCX activity, induced OPCs proliferation and [Na+]i accumulation. By contrast, 2 days of BED washout after 4 days of treatment significantly upregulated low molecular weight NCX3 proteins, reversed NCX activity, and increased intracellular [Ca2+]i. This BED-free effect was accompanied by an upregulation of NCX3 expression in oligodendrocyte processes and accelerated expression of myelin markers in rat primary oligodendrocytes. Collectively, our findings show that the pharmacological inhibition of the NCX3 exchanger with BED blocker maybe followed by a rebound increase in NCX3 expression and reversal activity that accelerate myelin sheet formation in oligodendrocytes. In addition, they indicate that a particular attention should be paid to the use of NCX inhibitors for possible rebound effects, and suggest that further studies will be necessary to investigate whether selective pharmacological modulation of NCX3 exchanger may be exploited to benefit demyelination and remyelination in demyelinating diseases.

Cold Hardiness Dynamics and Spring Phenology: Climate-Driven Changes and New Molecular Insights Into Grapevine Adaptive Potential.

Climate change has become a topic of increasing significance in viticulture, severely challenged by this issue. Average global temperatures are increasing, but frost events, with a large variability depending on geographical locations, have been predicted to be a potential risk for grapevine cultivation. Grape cold hardiness encompasses both midwinter and spring frost hardiness, whereas the avoidance of spring frost damage due to late budbreak is crucial in cold resilience. Cold hardiness kinetics and budbreak phenology are closely related and affected by bud's dormancy state. On the other hand, budbreak progress is also affected by temperatures during both winter and spring. Genetic control of bud phenology in grapevine is still largely undiscovered, but several studies have recently aimed at identifying the molecular drivers of cold hardiness loss and the mechanisms that control deacclimation and budbreak. A review of these related traits and their variability in different genotypes is proposed, possibly contributing to develop the sustainability of grapevine production as climate-related challenges rise.

Treatment of mycobacteriosis in a patient with compatible symptoms after a cesarean delivery.

This study aims to report the diagnostic course and treatment of a fast-growing mycobacteria infection after cesarean delivery. We report the case of a 37-year-old woman admitted to the Infectious Diseases' Clinic of the Hospital das Clinicas da Universidade Federal de Pernambuco, Pernambuco State, Brazil, four months after a cesarean section, presenting with healing difficulties and located pain outside the surgical site. The first diagnosis was a probable rejection of the sutures that were not absorbed, but based on the clinical signs, reported history, complementary laboratory tests and no response to treatment with the conventional antibiotic therapy (cephalosporins/quinolones) prescribed, the ultimate diagnosis was a mycobacteriosis caused by Micobacterium fortuitum. Since fast-growing mycobacteria do not easily penetrate host tissues, they is mainly related to post-trauma or post-surgical procedures. It is extremely important to call attention to these occurrences in the gynecological-obsthetric field. Treatment for mycobacteriosis is often complicated because of the side effects of antibiotics, especially the ototoxicity of amikacin.

Echocardiographic Parameters and Mortality in Pediatric Sepsis: A Systematic Review and Meta-Analysis.

OBJECTIVE: We conducted a systematic review and meta-analysis to investigate the prognostic value of echocardiographic parameters in pediatric septic patients. DATA SOURCES: MEDLINE, PubMed, and EMBASE (last update April 5, 2020). STUDY SELECTION: Observational studies of pediatric sepsis providing echocardiographic parameters in relation to mortality. DATA EXTRACTION: Echocardiography data were categorized as those describing left ventricular systolic or diastolic function, right ventricular function, and strain echocardiography parameters. Data from neonates and children were considered separately. Analysis is reported as standardized mean difference and 95% CI. DATA SYNTHESIS: We included data from 14 articles (n = 5 neonates, n = 9 children). The fractional shortening was the most commonly reported variable (11 studies, n = 555 patients) and we did not identify an association with mortality (standardized mean difference 0.22, 95% CI [-0.02 to 0.47]; p = 0.07, I2 = 28%). In addition, we did not find any association with mortality also for left ventricular ejection fraction (nine studies, n = 417; standardized mean difference 0.06, 95% CI [-0.27 to 0.40]; p = 0.72, I2 = 51%), peak velocity of systolic mitral annular motion determined by tissue Doppler imaging wave (four studies, n = 178; standardized mean difference -0.01, 95% CI [-0.34 to 0.33]; p = 0.97, I2 = 0%), and myocardial performance index (five studies, n = 219; standardized mean difference -0.51, 95% CI [-1.10 to 0.08]; p = 0.09, I2 = 63%). However, in regard to left ventricular diastolic function, there was an association with mortality for higher early wave of transmitral flow/peak velocity of early diastolic mitral annular motion determined by tissue Doppler imaging ratio (four studies, n = 189, standardized mean difference -0.45, 95% CI [-0.80 to -0.10]; p = 0.01, I2 = 0%) or lower peak velocity of early diastolic mitral annular motion determined by tissue Doppler imaging wave (three studies, n = 159; standardized mean difference 0.49, 95% CI [0.13-0.85]; p = 0.008, I2 = 0%). We did not find any association with mortality for early wave of transmitral flow/late (atrial) wave of trans-mitral flow ratio (six studies, n = 273; standardized mean difference 0.28, 95% CI [-0.42 to 0.99]; p = 0.43, I2 = 81%) and peak velocity of systolic mitral annular motion determined by tissue Doppler imaging wave measured at the tricuspid annulus (three studies, n = 148; standardized mean difference -0.18, 95% CI [-0.53 to 0.17]; p = 0.32, I2 = 0%). Only a few studies were conducted with strain echocardiography. CONCLUSIONS: This meta-analysis of echocardiography parameters in pediatric sepsis failed to find any association between the measures of left ventricular systolic or right ventricular function and mortality. However, mortality was associated with higher early wave of transmitral flow/peak velocity of early diastolic mitral annular motion determined by tissue Doppler imaging or lower peak velocity of early diastolic mitral annular motion determined by tissue Doppler imaging, indicating possible importance of left ventricular diastolic dysfunction. These are preliminary findings because of high clinical heterogeneity in the studies to date.

Pregnancy in an Asymptomatic Woman with Porencephalic and Arachnoid Cysts.

A 25-year-old woman presented to the obstetric clinic in her first pregnancy. The patient was accompanied by her mother who reported an episode of intracerebral hemorrhage after birth and also remembered access to the emergency department after generalized tonic-clonic seizure as an infant. She was not able to describe the therapy for seizure preventions and even when and why it was suspended, but she affirmed that no residual neurological consequences were detected in the following years. Actually, the pregnant woman was in good health without neurological symptoms nor assumed any therapy. A neurologist reviewed the patient's CT scan in which arachnoid cyst and porencephalic cyst were evident, and he assessed that no abnormalities were found in motor, sensory, and mental state examination. EEG did not show any epileptiform or seizure-like activity. No antiepileptic drug was prescribed due to the absence of symptoms since many years. The patient had no neurological symptoms during pregnancy or obstetric complications and delivered at term a healthy baby through a caesarean section. She breastfed, and after two years, the patient and the baby are healthy. The association of porencephalic and arachnoid cyst in pregnancy is an extremely rare neurological condition that needs a multidisciplinary counseling in pregnancy, but an uneventful course is possible.

Renal impairment in Alport syndrome pregnant woman: Case report and review of the literature.

Pregnant women affected by Alport syndrome often struggle with worsening of renal function during pregnancy. We focused the attention on the optimal management of the kidney disease in these women in order to avoid maternal-fetal complications.

Pre-symptomatic modified phytohormone profile is associated with lower phytoplasma titres in an Arabidopsis seor1ko line.

The proteins AtSEOR1 and AtSEOR2 occur as conjugates in the form of filaments in sieve elements of Arabidopsis thaliana. A reduced phytoplasma titre found in infected defective-mutant Atseor1ko plants in previous work raised the speculation that non-conjugated SEOR2 is involved in the phytohormone-mediated suppression of Chrysanthemum Yellows (CY)-phytoplasma infection transmitted by Euscelidius variegatus (Ev). This early and long-lasting SEOR2 impact was revealed in Atseor1ko plants by the lack of detectable phytoplasmas at an early stage of infection (symptomless plants) and a lower phytoplasma titre at a later stage (fully symptomatic plants). The high insect survival rate on Atseor1ko line and the proof of phytoplasma infection at the end of the acquisition access period confirmed the high transmission efficiency of CY-phytoplasma by the vectors. Transmission electron microscopy analysis ruled out a direct role of SE filament proteins in physical phytoplasma containment. Time-correlated HPLC-MS/MS-based phytohormone analyses revealed increased jasmonate levels in midribs of Atseor1ko plants at an early stage of infection and appreciably enhanced levels of indole acetic acid and abscisic acid at the early and late stages. Effects of Ev-probing on phytohormone levels was not found. The results suggest that SEOR2 interferes with phytohormonal pathways in Arabidopsis midrib tissues in order to establish early defensive responses to phytoplasma infection.