Increasing the efficiency of CRISPR/Cas9-mediated genome editing in the citrus postharvest pathogen Penicillium digitatum.

BACKGROUND: Penicillium digitatum is a fungal plant pathogen that causes the green mold disease in harvested citrus fruits. Due to its economical relevance, many efforts have focused on the development of genetic engineering tools for this fungus. Adaptation of the CRISPR/Cas9 technology was previously accomplished with self-replicative AMA1-based plasmids for marker-free gene editing, but the resulting efficiency (10%) limited its practical implementation. In this study, we aimed to enhance the efficiency of the CRISPR/Cas9-mediated gene editing in P. digitatum to facilitate its practical use. RESULTS: Increasing the culture time by performing additional culture streaks under selection conditions in a medium that promotes slower growth rates significantly improved the gene editing efficiency in P. digitatum up to 54-83%. To prove this, we disrupted five candidate genes that were chosen based on our previous high-throughput gene expression studies aimed at elucidating the transcriptomic response of P. digitatum to the antifungal protein PdAfpB. Two of these genes lead to visual phenotypic changes (PDIG_53730/pksP, and PDIG_54100/arp2) and allowed to start the protocol optimization. The other three candidates (PDIG_56860, PDIG_33760/rodA and PDIG_68680/dfg5) had no visually associated phenotype and were targeted to confirm the high efficiency of the protocol. CONCLUSION: Genome editing efficiency of P. digitatum was significantly increased from 10% to up to 83% through the modification of the selection methodology, which demonstrates the feasibility of the CRISPR/Cas9 system for gene disruption in this phytopathogenic fungus. Moreover, the approach described in this study might help increase CRISPR/Cas9 gene editing efficiencies in other economically relevant fungal species for which editing efficiency via CRISPR/Cas9 is still low.

First Molecular Diagnosis of Oestrus ovis (Linnaeus, 1758) Larvae Causing Conjunctival Ophthalmomyiasis in Mexico City, Mexico.

PURPOSE: Human ophthalmomyiasis is a rare ocular parasitosis that results from the accidental infestation of dipteran larvae of several species, including Oestrus ovis (Linnaeus, 1758). This study aims to present the fourth documented human case of ophthalmomyiasis in Mexico, identifying the etiological agent through morphological and molecular analyses. Additionally, we investigated the phylogenetic position and genetic distances among different specimens globally characterized based on mitochondrial Cox1 sequences. METHODS: A total of five larval specimens were extracted from the patient's eye, with two specimens allocated for identification based on morphological features using a stereomicroscope, and the remaining three preserved in absolute ethanol, one of them used for subsequent analysis using molecular methods. The mitochondrial Cox1 region was amplified and sequenced using automated Sanger sequencing. The resulting sequence was deposited in GenBank under accession number OR440699 and subjected to BlastN analysis against 35 other Cox1 sequences of O. ovis from GenBank. The identity and phylogenetic position of the strains were further explored using parsimony and maximum likelihood phylogenetic methods. RESULTS: Morphological examination of the larval specimens extracted from the patient's eye unequivocally identified them as O. ovis species. BlastN analysis and comprehensive phylogenetic investigations involving a total of 36 Cox1 sequences confirmed the taxonomic identity of the larvae. Notably, our sequence was positioned within the cluster formed by the Brazilian and two Iranian samples. This finding underscores a shared genetic ancestry among these distinct geographical isolates and provides valuable insights into the evolutionary relationships within O. ovis populations. CONCLUSION: The presence of O. ovis infestation in Mexico City suggests potential shifts in environmental conditions favoring fly proliferation, highlighting the need for vigilance in urban healthcare settings.

Sigh generation in preBötzinger Complex.

We explored neural mechanisms underlying sighing. Photostimulation of parafacial (pF) neuromedin B (NMB) or gastrin releasing peptide (GRP), or preBötzinger Complex (preBötC) NMBR or GRPR neurons elicited ectopic sighs with latency inversely related to time from preceding endogenous sigh. Of particular note, ectopic sighs could be produced without involvement of these peptides or their receptors in preBötC. Moreover, chemogenetic or optogenetic activation of preBötC SST neurons induced sighing, even in the presence of NMBR and/or GRPR antagonists. We propose that an increase in the excitability of preBötC NMBR or GRPR neurons not requiring activation of their peptide receptors activates partially overlapping pathways to generate sighs, and that preBötC SST neurons are a downstream element in the sigh generation circuit that converts normal breaths into sighs.

Studies on the biological role of the antifungal protein PeAfpA from Penicillium expansum by functional gene characterization and transcriptomic profiling.

Antifungal proteins (AFPs) from filamentous fungi have enormous potential as novel biomolecules for the control of fungal diseases. However, little is known about the biological roles of AFPs beyond their antifungal action. Penicillium expansum encodes three phylogenetically different AFPs (PeAfpA, PeAfpB and PeAfpC) with diverse profiles of antifungal activity. PeAfpA stands out as a highly active AFP that is naturally produced at high yields. Here, we provide new data about the function of PeAfpA in P. expansum through phenotypical characterization and transcriptomic studies of null mutants of the corresponding afpA gene. Mutation of afpA did not affect axenic growth, conidiation, virulence, stress responses or sensitivity towards P. expansum AFPs. However, RNA sequencing evidenced a massive transcriptomic change linked to the onset of PeAfpA production. We identified two large gene expression clusters putatively involved in PeAfpA function, which correspond to genes induced or repressed with the production of PeAfpA. Functional enrichment analysis unveiled significant changes in genes related to fungal cell wall remodeling, mobilization of carbohydrates and plasma membrane transporters. This study also shows a putative co-regulation between the three afp genes. Overall, our transcriptomic analyses provide valuable insights for further understanding the biological functions of AFPs.

Cell Membrane Tension Gradients, Membrane Flows, and Cellular Processes.

Cell membrane tension affects and is affected by many fundamental cellular processes, yet it is poorly understood. Recent experiments show that membrane tension can propagate at vastly different speeds in different cell types, reflecting physiological adaptations. Here we briefly review the current knowledge about membrane tension gradients, membrane flows, and their physiological context.

Nav1.8 in small dorsal root ganglion neurons contributes to vincristine-induced mechanical allodynia.

Vincristine-induced peripheral neuropathy (VIPN) is a common side effect of vincristine treatment, which is accompanied by pain and can be dose-limiting. The molecular mechanisms that underlie vincristine-induced pain are not well understood. We have established an animal model to investigate pathophysiological mechanisms of vincristine induced pain. Our previous studies have shown that the tetrodotoxin-sensitive (TTX-S) voltage-gated sodium channel NaV1.6 in medium-diameter dorsal root ganglion (DRG) neurons contributes to the maintenance of vincristine-induced allodynia. In this study, we investigated the effects of vincristine administration on excitability in small-diameter DRG neurons and whether the tetrodotoxin-resistant (TTX-R) NaV1.8 channels contribute to mechanical allodynia. Current-clamp recordings demonstrated that small DRG neurons become hyper-excitable following vincristine treatment, with both reduced current threshold and increased firing frequency. Using voltage-clamp recordings in small DRG neurons we now show an increase in TTX-R current density and a -7.3 mV hyperpolarizing shift in V1/2 of activation of NaV1.8 channels in vincristine-treated animals, which likely contributes to the hyperexcitability that we observed in these neurons. Notably, vincristine treatment did not enhance excitability of small DRG neurons from NaV1.8 knockout mice, and the development of mechanical allodynia was delayed but not abrogated in these mice. Together, our data suggest that sodium channel NaV1.8 in small DRG neurons contributes to the development of vincristine-induced mechanical allodynia.

Real-World Retrospective Analysis of Alemtuzumab Outcomes in Relapsing-Remitting Multiple Sclerosis: The LEMCAM Study.

BACKGROUND: Alemtuzumab is a high-efficacy treatment approved for relapsing-remitting multiple sclerosis (RRMS). Although clinical trials and observational studies are consistent in showing its efficacy and manageable safety profile, further studies under clinical practice conditions are needed to further support its clinical use. OBJECTIVE: The aim of this observational retrospective study was to evaluate the effectiveness and safety of alemtuzumab to add to the current real-world evidence on the drug. METHODS: A cohort of 115 adult patients with RRMS treated with alemtuzumab between 2014 and 2020 was retrospectively followed up in five centers in Spain. Analysis included annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW), 6-month confirmed disability improvement (CDI), radiological activity, no evidence of disease activity (NEDA-3), and safety signals. Given the different follow-up periods among participants, ARR was calculated using the person-years method. CDI was defined as a ≥ 1.0-point decrease in Expanded Disability Status Scale (EDSS) score assessed in patients with a baseline EDSS score ≥ 2.0 confirmed 6 months apart. CDW was defined as a ≥ 1.0-point increase in EDSS score assessed in patients with a baseline EDSS score ≥ 1.0 (≥ 1.5 if baseline EDSS = 0), confirmed 6 months apart. RESULTS: ARR decreased from 1.9 (95% confidence interval 1.60-2.33) in the year prior to alemtuzumab initiation to 0.28 (0.17-0.37) after 1 year of treatment (87% reduction), and to 0.22 (0.13-0.35) after the second year. Over the entire follow-up period, ARR was 0.24 (0.18-0.30). At year 1, 75% of patients showed no signs of magnetic resonance imaging (MRI) activity and 70% at year 5. One percent of patients experienced 6-month CDW at year 1, 2.6% at year 2, 7.4% at year 3, and no patients over years 4 and 5. A total of 7.7% of patients achieved 6-month CDI in year 1, 3.6% in year 2, and maintained it at years 3 and 4. Most patients achieved annual NEDA-3: year 1, 72%; year 2, 79%; year 3, 80%; year 4, 89%; year 5, 75%. Infusion-related reactions were observed in 95% of patients and infections in 74%. Thyroid disorders occurred in 30% of patients, and only three patients developed immune thrombocytopenia. No cases of progressive multifocal leukoencephalopathy were reported. CONCLUSIONS: This study shows that alemtuzumab reduced the relapse rate and disability worsening in real-world clinical practice, with many patients achieving and sustaining NEDA-3 over time. The safety profile of alemtuzumab was consistent with previous findings, and no new or unexpected safety signals were observed. As this was an observational and retrospective study, the main limitation of not having all variables comprehensively available for all patients should be considered when interpreting results.

Anatomical sphincteroplasty as a surgical treatment for faecal incontinence: proposal for a global anatomical reconstructive surgical procedure and results from a case series.

The aim of this study is to describe the technical details and clinical and functional results of anatomical sphincteroplasty as a global reconstructive surgery for the treatment of faecal incontinence caused by anal sphincter lesions. This was a prospective, longitudinal study that included patients who underwent the anatomical sphincteroplasty procedure described here to treat complete sphincter damage. We have described the different technical steps in detail. We evaluated the intraoperative and postoperative complications rate, Cleveland Clinic Score (CCS), a modification of the CCS that included soiling (mCCS), the Faecal Incontinence Quality of Life Scale (FIQLS), and patient satisfaction. An endoanal ultrasound and anorectal manometric study were performed in all the patients. Forty-four patients were included with a mean of 40.5 months follow-up. The CCS reduced from 15 to 3.3 points and the mCCS from 18.5 to 4.5 points over the study period; p < 0.001. Excellent or good results were achieved in 93% of cases. Endoanal ultrasounds showed a good sphincter repair in 66% of the cases. Anorectal manometry showed an increase in the mean maximal resting pressure from 27.6 mmHg to 41.7 mmHg and of the maximal squeeze pressure from 57.9 to 93 mmHg (p < 0.001) with respect to the preoperative values. Anatomical sphincteroplasty is a surgical proposal for the global anatomical reconstruction of anal sphincter lesions, even in cases of very severe damage. The procedure is safe and produced excellent clinical and functional results after a medium-term follow-up.

Anandamide and WIN 55212-2 Afford Protection in Rat Brain Mitochondria in a Toxic Model Induced by 3-Nitropropionic Acid: an In Vitro Study.

Mitochondrial dysfunction plays a key role in the development of neurodegenerative disorders. In contrast, the regulation of the endocannabinoid system has been shown to promote neuroprotection in different neurotoxic paradigms. The existence of an active form of the cannabinoid receptor 1 (CB1R) in mitochondrial membranes (mitCB1R), which might exert its effects through the same signaling mechanisms as the cell membrane CB1R, has been shown to regulate mitochondrial activity. Although there is evidence suggesting that some cannabinoids may induce protective effects on isolated mitochondria, substantial evidence on the role of cannabinoids in mitochondria remains to be explored. In this work, we developed a toxic model of mitochondrial dysfunction induced by exposure of brain mitochondria to the succinate dehydrogenase inhibitor 3-nitropropionic acid (3-NP). Mitochondria were also pre-incubated with the endogenous agonist anandamide (AEA) and the synthetic CB1R agonist WIN 55212-2 to evaluate their protective effects. Mitochondrial reduction capacity, reactive oxygen species (ROS) formation, and mitochondrial swelling were assessed as toxic markers. While 3-NP decreased the mitochondrial reduction capacity and augmented mitochondrial ROS formation and swelling, both AEA and WIN 55212-2 ameliorated these toxic effects. To explore the possible involvement of mitCB1R activation on the protective effects of AEA and WIN 55212-2, mitochondria were also pre-incubated in the presence of the selective CB1R antagonist AM281, which completely reverted the protective effects of the cannabinoids to levels similar to those evoked by 3-NP. These results show partial protective effects of cannabinoids, suggesting that mitCB1R activation may be involved in the recovery of compromised mitochondrial activity, related to reduction of ROS formation and further prevention of mitochondrial swelling.

Reproductive justice for Black, Indigenous, Women of Color: Uprooting race and colonialism.

Historically, atrocities against Black, Indigenous, and Women of Color's (BIWoC) reproductive rights have been committed and continue to take place in contemporary society. The atrocities against BIWoC have been fueled by White supremacy ideology of the "desirable race" and colonial views toward controlling poverty and population growth, particularly that of "undesirable" races and ethnicities. Grounded in Critical Race Theory, this paper aims to provide a critical analysis of historical and contemporary violations of BIWoC reproductive rights; discuss interventions based on empowerment and advocacy principles designed to promote women's reproductive justice; and discuss implications for future research, action, and policy from the lenses of Critical Race Theory and Community Psychology. This paper contributes to the special issue by critically analyzing historical and contemporary racism and colonialism against BIWoC, discussing implications for future research and practice, and making policy recommendations.

4E-BP1-dependent translation in nociceptors controls mechanical hypersensitivity via TRIM32/type I interferon signaling.

Activation of the mechanistic target of rapamycin complex 1 (mTORC1) contributes to the development of chronic pain. However, the specific mechanisms by which mTORC1 causes hypersensitivity remain elusive. The eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) is a key mTORC1 downstream effector that represses translation initiation. Here, we show that nociceptor-specific deletion of 4E-BP1, mimicking activation of mTORC1-dependent translation, is sufficient to cause mechanical hypersensitivity. Using translating ribosome affinity purification in nociceptors lacking 4E-BP1, we identified a pronounced translational up-regulation of tripartite motif-containing protein 32 (TRIM32), an E3 ubiquitin ligase that promotes interferon signaling. Down-regulation of TRIM32 in nociceptors or blocking type I interferon signaling reversed the mechanical hypersensitivity in mice lacking 4E-BP1. Furthermore, nociceptor-specific ablation of TRIM32 alleviated mechanical hypersensitivity caused by tissue inflammation. These results show that mTORC1 in nociceptors promotes hypersensitivity via 4E-BP1-dependent up-regulation of TRIM32/interferon signaling and identify TRIM32 as a therapeutic target in inflammatory pain.

Analysis of humoral and cellular immunity after SARS-CoV-2 vaccination in patients with multiple sclerosis treated with immunomodulatory drugs.

We analyzed immune response to SARS-CoV-2 vaccination by measuring specific IgG titers and T-cell reactivity to different SARS-CoV-2 peptides in multiple sclerosis patients taking different disease-modifying treatments. Of the 88 patients included, 72 developed any kind of immune response after vaccination. Although DMTs such as fingolimod and anti-CD20+ treatments prevented patients from developing a robust humoral response to the vaccine, most of them were still able to develop a cellular response, which could be crucial for long-term immunity. It is probably advisable that all MS patients take additional/booster doses to increase their humoral and/or cellular immune response to SARS-CoV-2.

Case Report: Role of Anterior Segment Optical Coherence Tomography for Managing Failed Endothelial Keratoplasty Graft.

SIGNIFICANCE: Some patients show poor visual outcomes after Descemet stripping automated endothelial keratoplasty. In such cases, secondary Descemet membrane endothelial keratoplasty can be performed to achieve complete visual recovery. Anterior segment optical coherence tomography (AS-OCT) is a valuable tool for the follow-up of posterior lamellar keratoplasty outcomes and complications. PURPOSE: This study aimed to report the clinical outcome of secondary Descemet membrane endothelial keratoplasty for managing poor visual results in a patient with graft failure after a previous Descemet stripping automated endothelial keratoplasty, highlighting the importance of AS-OCT in the follow-up of endothelial keratoplasty. CASE REPORT: A 38-year-old woman with high myopia underwent Descemet stripping automated endothelial keratoplasty for bullous keratopathy after explantation of an angle-supported phakic intraocular lens. Two years after keratoplasty, the patient experienced poor visual acuity (counting fingers), and significant corneal edema was observed on clinical examination hindering visualization of the anterior chamber structures. Anterior segment optical coherence tomography showed a failed and thickened graft adhering well to the recipient cornea in an anterior chamber without other comorbidities. Therefore, the graft was removed and replaced with a Descemet membrane endothelial keratoplasty graft without any complications. One year later, the clinical outcome was evaluated by comparing the pre-operative and post-operative best-corrected visual acuity, biomicroscopy findings, endothelial cell density, and corneal central thickness. CONCLUSIONS: Anterior segment optical coherence tomography is an important tool when deciding on the surgical technique to be applied and for the post-surgical monitoring of endothelial corneal grafts. This case demonstrates the successful management of Descemet stripping automated endothelial keratoplasty graft failure with Descemet membrane endothelial keratoplasty graft, highlighting the importance of AS-OCT in detecting complications such as graft dislocation and primary graft failure. In addition, corneal thickness measured using AS-OCT serves as a critical predictor of graft failure, as observed in this case.

The endocrine disruptor DE-79 alters oxytocinergic transmission and sexual behavior expression in male rats.

Polybrominated diphenyl ethers (PBDEs), used as flame retardants are persistent organic pollutants exerting important health effects. PBDEs with >5 bromide substitutions were considered less harmful and therefore extensively used commercially. DE-79 was a widely used PBDE mixture of hexa-, hepta-, octa- and nona-brominated compounds that increases vasopressin (AVP) production. AVP and oxytocin (OT) are both produced in neurons of the supraoptic (SON) and paraventricular (PVN) hypothalamic nuclei projecting to the neurohypophysis and to brain regions involved in copulatory behavior. OT plays an important role in male copulation. Since DE-79 alters AVP expression in the SON and PVN, it might also modify OT content and alter male sexual behavior. We analyzed if repeated DE-79 exposure of adult male rats affected OT content and OT receptor (OTR) density in the SON, PVN, medial preoptic area (mPOA), ventral tegmental area, nucleus accumbens, and amygdala, and if male copulatory behavior was affected. We show that DE-79 exposure produces a generalized decrease in brain OT immunoreactivity, increases OTR density in all brain regions analyzed but the mPOA, and reduces the ejaculatory threshold after a first ejaculation. The documented ejaculation-induced OT release might participate in this last effect. Thus, one-week DE-79 exposure alters the OT-OTR system and modifies male rat sexual performance. Based on the literature it could be speculated that these effects are related to the putative endocrine disrupting actions of DE-79, ultimately altering brain OT levels and OTR expression that might affect copulation and other important OT-mediated brain functions.

Is a sFlt-1/PlGF cutoff of 38 suitable to predict adverse outcomes in pregnancies with abnormal uterine artery Doppler velocimetry in the second trimester?

OBJECTIVE: To determine the optimal cutoff value for the soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio to predict maternal and fetal adverse events in pregnancies with uterine artery Doppler scans results above the 95th percentile in the late second trimester. STUDY DESIGN: Retrospective, observational cohort study on 116 asyntomatic patients with abnormal uterine artery Doppler scans at gestational week 25. The sFlt-1/PlGF ratio was determined within the weeks 25 to 29 of gestation and ROC curve analysis performed. The diagnostic validity of different cutoff values to predict severe maternal and fetal complications, i.e. preeclampsia, fetal growth restriction, placental abruption, and fetal death, was analyzed. MAIN OUTCOME MEASURES: An ideal cutoff for sFlt-1/PlGF ratios in pregnancies with abnormal uterine artery Doppler in the second trimester. RESULTS: Applying a cutoff point of 38, the area under the ROC curve was 0.89, generally considered low risk in fetal and maternal complication prediction. The sensitivity was 32.1%, the specificity 98.4%, the positive predictive value (PPV) 94.4%, and the negative predictive value (NPV) 63.3%. A cutoff value of 10, leading to the highest Youden index, performed best at detecting overall complications, increasing sensitivity to 69.8% and the NPV to 76.8%. at the cost of a reduced specificity and PPV. CONCLUSIONS: In pregnancies with abnormal uterine artery Doppler in the second trimester, an sFlt-1/PlGF cutoff value greater than equal to 38 improves its predictive power for adverse events.

Quantitative risk assessment of African swine fever introduction into Spain by legal import of swine products.

African swine fever (ASF) is currently threatening the global swine industry. Its unstoppable global spread poses a serious risk to Spain, one of the world's leading producers. Over the past years, there has been an increased global burden of ASF not only in swine but also swine products. Unfortunately, many pigs are not diagnosed before slaughter and their products are used for human consumption. These ASF-contaminated products are only a source for new ASF outbreaks when they are consumed by domestic pigs or wild boar, which may happen either by swill feeding or landfill access. This study presents a quantitative stochastic risk assessment model for the introduction of ASF into Spain via the legal import of swine products, specifically pork and pork products. Entry assessment, exposure assessment, consequence assessment and risk estimation were carried out. The results suggest an annual probability of ASF introduction into Spain of 1.74 × 10-4, the highest risk being represented by Hungary, Portugal, and Poland. Monthly risk distribution is homogeneously distributed throughout the year. Illegal trade and pork product movement for own consumption (e.g., air and ship passenger luggage) have not been taken into account due to the lack of available, accredited data sources. This limitation may have influenced the model's outcomes and, the risk of introduction might be higher than that estimated. Nevertheless, the results presented herein would contribute to allocating resources to areas at higher risk, improving prevention and control strategies and, ultimately, would help reduce the risk of ASF introduction into Spain.

Papel de la reparación muscular en el tratamiento de la incontinencia anal

La incontinencia anal (IA) tiene una alta prevalencia en la sociedad, aumenta con la edad, presenta elevados costes económicos y tiene un importante impacto negativo en la calidad de vida de los pacientes que la padecen. El tratamiento quirúrgico se reserva para aquellos pacientes que no responden a medidas conservadoras. Clásicamente, las técnicas de reparación muscular han jugado un papel principal en el tratamiento de la IA, sobre todo en aquellos casos en los que había un defecto del complejo esfinteriano, siendo la más extendida la esfinteroplastía solapante y reservando técnicas más complejas como la graciloplastía para casos con lesiones esfinterianas catastróficas. Otras técnicas como la reparación total del suelo pélvico se encuentran en desuso por sus pobres resultados.

Anal Incontinence (AI) is a prevalent disease, increases with aging, has high economic costs and a deep impact in the quality of life of the patients who suffer it. Surgical treatment is proposed in patients with no-response to medical therapy. Muscle repair techniques have been the main approach in AI, specially when there is a sphincteric damage. Overlapping sphincteroplasty is the most common technique and graciloplasty is used when there is a wide damage in sphinteric complex. Some other techniques such as postanal or total pelvic floor repair are not used any more because of their poor results.

Excitatory neuron-specific suppression of the integrated stress response contributes to autism-related phenotypes in fragile X syndrome.

Dysregulation of protein synthesis is one of the key mechanisms underlying autism spectrum disorder (ASD). However, the role of a major pathway controlling protein synthesis, the integrated stress response (ISR), in ASD remains poorly understood. Here, we demonstrate that the main arm of the ISR, eIF2α phosphorylation (p-eIF2α), is suppressed in excitatory, but not inhibitory, neurons in a mouse model of fragile X syndrome (FXS; Fmr1-/y). We further show that the decrease in p-eIF2α is mediated via activation of mTORC1. Genetic reduction of p-eIF2α only in excitatory neurons is sufficient to increase general protein synthesis and cause autism-like behavior. In Fmr1-/y mice, restoration of p-eIF2α solely in excitatory neurons reverses elevated protein synthesis and rescues autism-related phenotypes. Thus, we reveal a previously unknown causal relationship between excitatory neuron-specific translational control via the ISR pathway, general protein synthesis, and core phenotypes reminiscent of autism in a mouse model of FXS.

Bronchogenic Cyst: Lessons Learned in 20 Years of Experience at a Tertiary Pediatric Center.

BACKGROUND: Bronchogenic cysts are benign congenital malformations of the primitive ventral foregut. The aim of this study is to analyze and report 20 years of experience in the diagnosis and treatment of bronchogenic cysts at a tertiary pediatric center. METHODS: A retrospective review was conducted of all patients diagnosed with a bronchogenic cyst between 2000-2020. Presence of symptoms, cyst location, surgical technique, postoperative complications, need for pleural drainage, and recurrence were reviewed. RESULTS: Forty-five children were included in the study. In 37 patients a partial resection of the cyst was done, followed by cauterization or chemical obliterateration with iodopovidone of the mucosa of the remaining cyst wall that was adherent to the airway. A lobectomy was done in patients who had intrapulmonary cysts (n = 8). Cyst location was subcarinal in 23 (51.1%), paratracheal in 14 (31.1%), and intrapulmonary in eight patients (17.8%). The majority of subcarinal and paratracheal cysts (90%) were approached by thoracoscopy. Complications occurred in seven patients (15%): subcutaneous emphysema after pleural drain removal in one, extubation failure in two, reoperation due to bleeding in one, surgical site infection in one, bronchopleural fistula in one, and pneumothorax in one. Reoperation due to cyst recurrence was necessary in two patients (4.4%). Mean follow-up was 56 months (range, 0-115). CONCLUSION: A minimally invasive approach is a safe option for the management of paratracheal and subcarinal bronchogenic cysts with no history of infection in specialized pediatric surgery center. Thoracoscopic partial resection is a feasible option in most patients with subcarinal and paratracheal bronchogenic cysts with a low complication and reoperation rate. LEVEL OF EVIDENCE: IV.