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Bacillus thuringiensis is a widely used bacterial entomopathogen producing insecticidal toxins, some of which are expressed in insect-resistant transgenic crops. Surprisingly, the killing mechanism of B. thuringiensis remains controversial. In particular, the importance of the septicemia induced by the host midgut microbiota is still debated as a result of the lack of experimental evidence obtained without drastic manipulation of the midgut and its content. Here this key issue is addressed by RNAi-mediated silencing of an immune gene in a lepidopteran host Spodoptera littoralis, leaving the midgut microbiota unaltered. The resulting cellular immunosuppression was characterized by a reduced nodulation response, which was associated with a significant enhancement of host larvae mortality triggered by B. thuringiensis and a Cry toxin. This was determined by an uncontrolled proliferation of midgut bacteria, after entering the body cavity through toxin-induced epithelial lesions. Consequently, the hemolymphatic microbiota dramatically changed upon treatment with Cry1Ca toxin, showing a remarkable predominance of Serratia and Clostridium species, which switched from asymptomatic gut symbionts to hemocoelic pathogens. These experimental results demonstrate the important contribution of host enteric flora in B. thuringiensis-killing activity and provide a sound foundation for developing new insect control strategies aimed at enhancing the impact of biocontrol agents by reducing the immunocompetence of the host.

In Argentina, Thecaphora frezii is the causal agent of peanut smut, causing severe yield losses in peanut growing areas. In this work sequence data of the large ribosomal subunit (28S rDNA) of four T. frezii specimens from different production regions are provided. A fragment of about 650 bp was amplified by PCR from each of the isolates analyzed. The analysis of the sequences demonstrated 100 % identity among the four specimens and 92–96.3 % identity with sequences of other species of Thecaphora. This is the first study on molecular sequences of this pathogen.

Soil microbial populations can fluctuate in response to environmental changes and, therefore, are often used as biological indicators of soil quality. Soil chemical and physical parameters can also be used as indicators because they can vary in response to different management strategies. A long-term field trial was conducted to study the effects of different tillage systems (NT: no tillage, DH: disc harrow, and MP: moldboard plough), P fertilization (diammonium phosphate), and cattle grazing (in terms of crop residue consumption) in maize (Zea mays L.), sunflower (Heliantus annuus L.), and soybean (Glycine max L.) on soil biological, chemical, and physical parameters. The field trial was conducted for four crop years (2000/2001, 2001/2002, 2002/2003, and 2003/2004). Soil populations of Actinomycetes, Trichoderma spp., and Gliocladium spp. were 49% higher under conservation tillage systems, in soil amended with diammonium phosphate (DAP) and not previously grazed. Management practices also influenced soil chemical parameters, especially organic matter content and total N, which were 10% and 55% higher under NT than under MP. Aggregate stability was 61% higher in NT than in MP, 15% higher in P-fertilized soil, and also 9% higher in not grazed strips, bulk density being 12% lower in NT systems compared with MP. DAP application and the absence of grazing also reduced bulk density (3%). Using conservation tillage systems, fertilizing crops with DAP, and avoiding grazing contribute to soil health preservation and enhanced crop production.

Background: Infertility is a highly meaningful issue with potentially life-changing consequences, and its incidence has been growing worldwide. Assisted reproductive technology (ART) has made giant strides in terms of treating many infertility conditions, despite the risk of developing ovarian hyperstimulation syndrome (OHSS), a potentially life-threatening complication. Methods: This narrative review draws upon scientific articles found in the PubMed database. The search spanned the 1990–2024 period. Search strings used included “OHSS” or “ovarian hyperstimulation” and “IVF” and “GnRH” and “hCG”; 1098 results were retrieved and were ultimately narrowed down to 111 suitable sources, i.e., relevant articles dealing with the condition’s underlying dynamics, management pathways, and evidence-based criteria and guidelines, crucial both from a clinical perspective and from the standpoint of medicolegal tenability. Results: The following features constitute OHSS risk factors: young age, low body weight, and polycystic ovarian syndrome (PCOS), among others. GnRH antagonist can substantially lower the risk of severe OHSS, compared to the long protocol with a gonadotropin-releasing hormone (GnRH) agonist. However, a mild or moderate form of OHSS is also possible if the antagonist protocol is used, especially when hCG is used for the final maturation of oocytes. For women at risk of OHSS, GnRH agonist trigger and the freeze-all strategy is advisable. OHSS is one of the most frequent complications, with a 30% rate in IVF cycles. Conclusion: Providing effective care for OHSS patients begins with early diagnosis, while also evaluating for comorbidities and complications. In addition to that, we should pay more attention to the psychological component of this complication and of infertility as a whole. Compliance with guidelines and evidence-based best practices is essential for medicolegal tenability.

Nonomuraea gerenzanensis ATCC 39727 produces the glycopeptide antibiotic A40926, which is the natural precursor of the semi-synthetic, last-resort drug dalbavancin. To reduce the cost of dalbavancin production, it is mandatory to improve the productivity of the producing strain. Here, we report that the exposure of N. gerenzanensis wild-type population to sub-inhibitory concentrations of A40926 led to the isolation of differently resistant phenotypes to which a diverse A40926 productivity was associated. The most resistant population (G, grand colonies) represented at least the 20% of the colonies growing on 2 µg/mL of A40926. It showed a stable phenotype after sub-culturing and a homogeneous profile of self-resistance to A40926 in population analysis profile (PAP) experiments. The less resistant population (P, petit) was represented by slow-growing colonies to which a lower A40926 productivity was associated. At bioreactor scale, the G variant produced twice more than the wild-type (ca. 400 mg/L A40926 versus less than 200 mg/L, respectively), paving the way for a rational strain improvement based on the selection of increasingly self-resistant colonies.

The enzyme protein kinase C ε (PKCε) plays an important role in pain signaling and represents a promising therapeutic target for the treatment of chronic pain. We designed and generated a small molecule inhibitor of PKCε, CP612, and examined its effect in a rodent model of chemotherapy-induced neuropathic pain produced by paclitaxel, which does not respond well to current therapeutics. In addition, many patients with chronic pain use opiates, which over time can become ineffective, and attempts to discontinue them can increase pain thereby promoting sustained opioid use. Therefore, we also investigated if CP612 alters pain due to opioid withdrawal. We found that CP612 attenuated hyperalgesia produced by paclitaxel, and it both prevented and reversed hyperalgesia induced by opioid withdrawal. It was not self-administered and did not affect morphine self-administration. These findings suggest that inhibition of PKCε is an effective, nonaddictive strategy to treat chemotherapy-induced neuropathic pain, with the added benefit of preventing increases in pain that occur as opioid treatment is discontinued. This latter property could benefit individuals with chronic pain who find it difficult to discontinue opioids.

Liver damage worsens the prognosis of coronavirus 19 disease (COVID-19). However, the best strategy to stratify mortality risk according to liver damage has not been established. The aim of this study is to test the predictive value of the validated Fibrosis-4 (FIB-4) Index and compared it to liver transaminases and to the AST-to-Platelet ratio index (APRI). Multicenter cohort study including 992 consecutive COVID-19 patients admitted to the Emergency Department. FIB-4 > 3.25 and APRI > 0.7 were used to define liver damage. Multivariable Cox regression and ROC curve analysis for mortality were performed. Secondary endpoints were (1) need for high-flow oxygen and (2) mechanical ventilation. 240 (24.2%) patients had a FIB-4 > 3.25. FIB-4 > 3.25 associated with an increased mortality (n = 119, log-rank test p < 0.001 and adjusted hazard ratio (HR) 1.72 (95% confidence interval [95%CI] 1.14–2.59, p = 0.010). ROC analysis for mortality showed that FIB-4 (AUC 0.734, 95% CI 0.705–0.761) had a higher predictive value than AST (p = 0.0018) and ALT (p < 0.0001). FIB-4 > 3.25 was also superior to APRI > 0.7 (AUC 0.58, 95% CI 0.553–0.615, p = 0.0008). Using an optimized cut-off > 2.76 (AUC 0.689, 95% CI 0.659–0.718, p < 0.0001), FIB-4 was superior to FIB-4 > 3.25 (p = 0.0302), APRI > 0.7 (p < 0.0001), AST > 51 (p = 0.0119) and ALT > 42 (p < 0.0001). FIB-4 was also associated with high-flow oxygen use (n = 255, HR 1.69, 95% CI 1.25–2.28, p = 0.001) and mechanical ventilation (n = 39, HR 2.07, 95% CI 1.03–4.19, p = 0.043). FIB-4 score predicts mortality better than liver transaminases and APRI score. FIB-4 score may be an easy tool to identify COVID-19 patients at worse prognosis in the emergency department.

On July 18, 2022, the New York State Department of Health (NYSDOH) notified CDC of detection of poliovirus type 2 in stool specimens from an unvaccinated immunocompetent young adult from Rockland County, New York, who was experiencing acute flaccid weakness. The patient initially experienced fever, neck stiffness, gastrointestinal symptoms, and limb weakness. The patient was hospitalized with possible acute flaccid myelitis (AFM). Vaccine-derived poliovirus type 2 (VDPV2) was detected in stool specimens obtained on days 11 and 12 after initial symptom onset. To date, related Sabin-like type 2 polioviruses have been detected in wastewater* in the patient's county of residence and in neighboring Orange County up to 25 days before (from samples originally collected for SARS-CoV-2 wastewater monitoring) and 41 days after the patient's symptom onset. The last U.S. case of polio caused by wild poliovirus occurred in 1979, and the World Health Organization Region of the Americas was declared polio-free in 1994. This report describes the second identification of community transmission of poliovirus in the United States since 1979; the previous instance, in 2005, was a type 1 VDPV (1). The occurrence of this case, combined with the identification of poliovirus in wastewater in neighboring Orange County, underscores the importance of maintaining high vaccination coverage to prevent paralytic polio in persons of all ages.

Background The aim of this protocol is to describe the study protocol changes made and subsequently implemented to the Pediatric Guideline Adherence and Outcomes (PEGASUS) Argentina randomized controlled trial (RCT) for care of children with severe traumatic brain injuries (TBI) imposed by the COVID-19 pandemic. The PEGASUS study group met in spring 2020 to evaluate available literature review guidance and the study design change or pausing options due to the potential interruption of research. Methods As a parallel cluster RCT, pediatric patients with severe TBIs are admitted to 8 control (usual care) and 8 intervention (PEGASUS program) hospitals in Argentina, Chile, and Paraguay. PEGASUS is an intervention that aims to increase guideline adherence and best practice care for improving patient outcomes using multi-level implementation science-based approaches. Strengths and weaknesses of proposed options were assessed and resulted in a decision to revert from a stepped wedge to a parallel cluster RCT but to not delay planned implementation. Discussion The parallel cluster design was considered more robust and flexible to secular interruptions and acceptable and feasible to the local study sites in this situation. Due to the early stage of the study, the team had flexibility to redesign and implement a design more compatible with the conditions of the research landscape in 2020 while balancing analytical methods and power, logistical and implementation feasibility, and acceptability. As of fall 2022, the PEGASUS RCT has been active for nearly 2 years of implementation and data collection, scheduled to be completed in in fall 2023. The experience of navigating research during this period will influence decisions about future research design, strategies, and contingencies. Trial registration Pediatric Guideline Adherence and Outcomes-Argentina. Registered with ClinicalTrials.gov Identifier NCT03896789 on April 1, 2019.

Ramoplanin is a glycolipodepsipeptide antibiotic obtained by fermentation of the Actinoplanes sp. ATCC 33076, isolated as a complex of three closely related components A1, A2 and A3, which differ in their fatty acid moiety. We have investigated the influence of L -leucine and L -valine, the biosynthetic precursors of the fatty acids in A2 and A3 factors, on the complex composition and antibiotic productivity. Addition of 5 g/litre of L -leucine at the time of inoculation increases antibiotic production and improves the production of A2 factor, which represents the active principle component under clinical development. Addition of L -valine in the same conditions modifies the composition of the complex towards the A3 factor but does not improve total antibiotic productivity. A possible explanation for the different actions of the two amino acids is presented.