Background and aims: Oral mucositis (OM) is common and distressing toxicity in children on chemotherapy. There is limited number of safe and effective therapeutic options available for OM. Ketamine oral rinse has shown promising results in few studies in adults. This randomized, double-blind placebo-controlled trial aimed to test the efficacy of ketamine mouthwash in reducing chemotherapy-induced severe OM pain in children. Methods: Children aged 8-18 years with severe OM were randomized to a single dose of ketamine mouthwash (4 mg/ml solution; dose 1 mg/kg) or a placebo. A sample size of 44 patients was determined. Pain score (6-point faces scale) was noted at baseline and 15, 30, 45, 60, 120, 180, and 240 min. The outcome variables were a reduction in pain score, need for rescue medications, and adverse events. Results: The baseline characteristics were comparable in the two groups. The mean OM pain at 60 min decreased by 1.64 points (CI 1.13-2.14) in the ketamine group and 1.32 points (CI 0.76-1.87) in the placebo group (p=0.425), with a group difference of 0.32 points. Rescue pain medication (at 60 min) was required in 13.6% in the ketamine group and 18.2% in the placebo group (p=1.000). There were no significant adverse events observed. Conclusions: Among children on cancer chemotherapy with severe OM, ketamine mouthwash at a dose of 1 mg/kg did not significantly reduce OM pain. It did not decrease the need for rescue pain medications. Further research is warranted to test higher doses of ketamine for a clinically significant effect.

The COVID-19 pandemic has remarkably impacted the hospital management and the profile of patients suffering from acute cardiovascular syndromes. Among them, acute infective endocarditis (AIE) represented a rather frequent part of these urgent/emergent procedures. The paper by Li and colleagues has clearly shown the higher risk features which patients with diagnosis of AIE presented at hospital admission during the first part (first and second waves) of the outbreak, often requiring challenging operations, but fortunately not associated with worse outcome if compared to results obtained prior to the SARS-2 pandemic. The report discussed herein presents several other aspects worth of discussion and comments, particularly in relation to hospital management and post-discharge outcome which certainly deserve to be highlighted, but also further investigations.

Introduction/Objectives: We evaluated the length of time immunocompromised children (ICC) remain positive for SARS-CoV-2, identified factors associated with viral persistence and determined cycle threshold (CT) values of children with viral persistence as a surrogate of viral load. Methods: We conducted a retrospective cohort study of ICC at a pediatric hospital from March 2020-2021. Immunocompromised status was defined as primary, secondary or acquired due to medical comorbidities/immunosuppressive treatment. The primary outcome was time to first-of-two consecutive negative SARS-CoV-2 Polymerase chain reaction (PCR) tests at least 24 hours apart. Testing of sequential clinical specimens from the same subject was conducted using the Centers for Disease Control (CDC) 2019-nCoV Real-Time RT-PCR Diagnostic Panel assay. Descriptive statistics, Kaplan-Meier curve median event times and log-rank-sum tests were used to compare outcomes between groups. Results: Ninety-one children met inclusion criteria. Median age was 15.5 years (IQR 8-18 yrs), 64% were male, 58% were white, and 43% were Hispanic/Latinx. Most (67%) were tested in outpatient settings and 58% were asymptomatic. The median time to two negative tests was 42 days (IQR 25.0,55.0), with no differences in median time by illness presentation or level of immunosuppression. Seven children had >1 sample available for repeat testing, and 5/7 (71%) children had initial CT values of <30, (moderate to high viral load); 4 children had CT values of <30 3-4 weeks later, suggesting persistent moderate to high viral loads. Conclusions: Most ICC with SARS-CoV-2 infection had mild disease, with prolonged viral persistence >6 weeks and moderate to high viral load.

Background: The COVID-19 pandemic has caused a global havoc with our limited understanding of the SARS-CoV-2, disease manifestations and management. Inadequacy of available data in pediatric patients coupled with evolving disease course makes it imperative to conduct a meta-analysis assessing the results of pediatric COVID-19 studies over the course of the pandemic. Methods: A random-effect meta-analysis was conducted using PRISMA guidelines. Two databases were screened for pediatric COVID-19 studies and selected articles reviewed for demographic, co-morbidities, clinical manifestations, laboratory and radiological evaluation, treatment and outcomes. Prevalence with mean and 95% confidence interval was calculated. Results: Out of 1703 articles, 37 articles comprising of 993 patients for a period of over six months and 72 variables were selected. This meta-analysis revealed that one-fourth of patients were asymptomatic (23.8%, 95% CI 17.6-31.2%) Fever (52.5%, 95% CI 45.7–59.1%) and cough (47.6%, 95% CI 41.2–54.0%) were the most common symptoms. The most frequently encountered white blood count abnormalities were neutropenia (16.6%, 95% CI 10.2-25.8%), lymphocytosis (15.3%, 95% CI 9.9–23.0%) and leukopenia (13.9%, 95% CI 10.1–18.8%). Ground glass opacities were the most common radiological finding of children with COVID-19 (35.9%, 95% CI 29.4-43%).  The hospitalization rate was 95.9% (95% CI 91.9-98.0%) of which 11.2% (95% CI 4.7-24.2) were ICU admissions, and 4.2% (95% CI 2.6-6.9%) died. Conclusion: Majority of pediatric patients are asymptomatic or have mild manifestations similar to other upper respiratory viruses. Serious disease and death occurred in 15.4%. More studies are needed from a wider geographic area as the pandemic continues.

In this case report, we present a 46-year-old lady who has developed a rapidly progressive heart failure after an episode of COVID-19. The pathologic examination of her endomyocardial biopsy specimens was compatible with GCM and she was successfully treated with a combined immunosuppressive therapy regimen.

Background: Patients who survived hospitalization for COVID-19 experienced varying durations of illness but the factors associated with prompt recovery are unknown. This study identifies factors differentiating hospitalized patients who recovered promptly vs. survived a prolonged course of illness due to COVID-19. Methods: This was a retrospective study from March-August 2020 of hospitalized adults with COVID-19 which were grouped based on time to recovery: short (≤ 3 days), intermediate (4-10 days), and prolonged (>10 days). Recovery was defined as resolution of fever, tachypnea, hypotension, extubation and return of mental status at baseline. Multivariate analysis was used to evaluate factors associated with prompt recovery. Results: Among 508 patients hospitalized for COVID-19, 401 (79%) survived. Of those, prompt recovery (within 3 days) was achieved in 43% (174/401) whereas 23% (92/401) recovered after a prolonged period of > 10 days. Overall, median age was 64 y with 73% admitted from home and 25% from a skilled nursing facility. Predictors for prompt recovery upon admission included female sex (OR, 1.8; 95% CI, 1.1-2.7; p = 0.01), no fever (OR, 1.6; 95% CI, 1.1-2.6; p = 0.03), longer time from symptom onset to hospitalization (OR, 1.1; 95% CI, 1.0-1.1; p = 0.001), no supplemental oxygen (OR, 1.9; 95% CI, 1.2-3.0; p = 0.004), no direct ICU admission (OR, 41.7; 95% CI, 2.4-740.4; p = 0.01) and absence of bacterial co-infections (OR, 2.5; 95% CI, 1.5-4.0, p = 0.0003). Conclusions: Our study provides relevant data that could help clinicians triage competing resources in health systems that are challenged by the ebb and flow of COVID-19 cases by identifying clinical features of COVID-19 patients who may require less intensive management including avoidance of unnecessary antibacterial therapy.

The chloroplast represents an attractive compartment for light-driven biosynthesis of recombinant products, and advanced synthetic biology tools are available for engineering the chloroplast genome (=plastome) of several algal and plant species. However, producing commercial lines will likely require several plastome manipulations, and this will present issues with respect to selectable markers: there are a limited number of markers available, these can be used only once in a serial engineering strategy, and it is undesirable to retain marker genes for antibiotic resistance in the final transplastome. To address these problems, we have designed a rapid iterative marker system for the green microalga Chlamydomonas reinhardtii that allows creation of marker-free transformants starting from wild-type strains. The system employs a dual marker encoding a fusion protein of E. coli aminoglycoside adenyltransferase (conferring spectinomycin resistance) and a variant of E. coli cytosine deaminase (conferring sensitivity to 5-fluorocytosine). Initial selection on spectinomycin allows stable transformants to be established and driven to homoplasmy. Subsequent selection on 5-fluorocytosine results in rapid loss of the dual marker through intramolecular recombination between the marker’s 3’UTR and the 3’UTR of the introduced transgene(s). We demonstrate the versatility of the CpPosNeg system by serial introduction of reporter genes into the plastome.

Mitotane is the only drug approved for treating adrenocortical carcinoma (ACC) by the FDA since 1959, despite the controversy regarding its efficacy in prolonging patient survival. This drug has cytotoxic effects on tumor tissue by inducing cell death and antisecretory effects on adrenal cells by inhibiting the synthesis of adrenocortical steroids involved in the pathogenesis of ACC. To reach the therapeutic plasma concentration, high doses of mitotane are usually necessary, which may result in several adverse effects. This suggests that important pharmacological features are involved in the mechanisms of action of this drug, such as first pass metabolism, tissue accumulation, and extensive time needed for drug elimination. However, few studies have reported the pharmacological aspects of mitotane, and they did not provide sufficient evidence regarding monitoring mitotane’s therapeutic effects. Therefore, this review summarized the chemistry, pharmacokinetics and pharmacodynamics, therapeutic effects, toxic effects, and new perspectives of mitotane treatment that are currently under investigation. Understanding the pharmacological profile of mitotane can improve the monitoring and efficacy of this drug in ACC treatment and can further provide useful information for the development of new drugs with specific action against ACC with fewer adverse effects.

Since the first description of phloem sap composition nearly 60 years ago, it is generally assumed that phloem sap does not contain nitrate and that there is little or no backflow of nitrate from shoots to roots. While it is true that nitrate can occasionally be absent from phloem sap, there is now substantial evidence that phloem can carry nitrate and furthermore, transporters involved in nitrate redistribution to shoot sink organs and roots have been found. This raises the question of why nitrate may or may not be present in phloem sap, why its concentration is generally kept low, and whether plant shoot-root nutrient cycling also involves nitrate. We propose here that phloem sap nitrate is not only an essential component of plant nutritional signaling but also contributes to physical properties of phloem sap and as such, its concentration is controlled to ensure proper coordination of plant development and nutrient transport.

Saltwater- and freshwater environments have opposing physiological challenges, yet, there are fish species that are able to enter both habitats during short time-spans, and as individuals they must therefore adjust quickly to osmoregulatory contrasts. In this study, we conducted an experiment to test for plastic responses to abrupt sainity changes in two poplulations of threespine stickleback, Gasterosteus aculeatus, representing two ecotypes (freshwater and ancestral saltwater). We exposed both ecotypes to abrupt native (control treatment) and non-native salinities (0 and 30‰) and sampled gill-tissue for transcriptomic analyses after six hours exposure. To investigate genomic responses to salinity, we analysed four different comparisons; one for each ecotype (in their control and exposure salinity; 1 and 2), one between ecotypes in their control salinity (3), and the fourth comparison included all transcripts identified in (3) that did not show any expressional changes within ecotype in either the control or the exposed salinity (4). Abrupt salinity transfer affected the expression of 10 and 1530 transcripts for the saltwater and freshwater ecotype, respectively, and 1314 were differentially expressed between the controls, including 502 that were not affected by salinity within ecotype (fixed expression). In total, these results indicate that factors other than genomic expressional plasticity are important for osmoregulation in stickleback, due to the need for opposite physiological pathways to survive the abrupt change in salinity.

Stevens-Johnson Syndrome (SJS) happen as a result of infection, side effects to medications or of unknown etiology. Carbamazepine is a common cause (SJS). Good history taking is crucial if clinically indicated treatment with carbamazepine. carbamazepine should be avoided with previous history of severe drug reaction like mast cell activation syndrome.

Understanding the structure and connectivity of coral populations is fundamental for developing marine conservation policies, especially in patchy environments such as archipelagos. The Nansei Islands, extending more than 1,000 km in southwestern Japan, are characterized by high levels of biodiversity and endemism, supported by coral reefs, although precise, detailed genetic attributes of corals are still largely unknown. In this study, we conducted population genomic analyses based on genome-wide, single-nucleotide polymorphisms (SNPs) of Acropora digitifera, a common species in the Nansei Islands, for which a complete genome is available. With ~24x sequencing coverage of entire genomes of 303 colonies collected at 21 locations, we identified more than four million genome-wide SNPs. While population structure analyses suggested weak genetic differentiation among sampled locations, the most southwestern location (the west end of the Yaeyama Islands) was genetically similar to the northernmost location (the Tanegashima Islands), separated by >1,000 km. Although examination of a migration network found a general tendency of northward migration along the Kuroshio Current, a substantial amount of southward migration was also detected, indicating important contributions of minor ocean currents to coral larval dispersal. Moreover, heterogeneity in the transition of effective population sizes among locations suggests different histories for individual subpopulations. The unexpected complexity of both past and present population dynamics in the Nansei Islands implies that heterogeneity of ocean currents and local environments, past and present, have influenced the population structure of this species, highlighting the importance of local scale assessments for effective coral restoration and management.

Beta-thalassaemia is one of the most significant haemoglobinopathies worldwide resulting in the synthesis of little or no β-globin chains. Without treatment, β-thalassaemia major is lethal within the first decade of life due to the complex pathophysiology which leads to wide clinical manifestations. Current clinical management for these patients solely relies on repeated transfusions followed by iron chelating therapy which can eventually results into multi-organ damage. A number of novel approaches to correct the resulting α/β globin chain imbalance are currently being developed. These include reactivation of foetal haemoglobin by pharmacological compounds, allogenic hematopoietic stem cell transplantation (HSCT) and gene therapy. Up to now, the only curative treatment for beta-thalassemia is HSCT, but this is a risky and costly procedure. Gene therapy either by gene addition or gene editing is emerging as a powerful approach to treat this disease. Gene addition is currently based on transplantation of autologous hematopoietic stem cells genetically modified with an integrating lentiviral vector expression the globin gene while gene editing involves the use of CRISPR/Cas9 to correct the causative mutation. Although the early outcomes of the clinical trials in gene therapy are showing promising results, they have also highlighted a number of limitations. In this review we will discuss about the current management strategies used to treat beta-thalassaemia and also focus on novel therapies.

Cas9 nucleases have become the most versatile tool for genome editing projects in a broad range of organisms. The recombinant production of Cas9 nuclease is desirable for in vitro activity assays or the preparation of ribonucleoproteins (RNPs) for DNA-free genome editing approaches. For the rapid production of Cas9, we explored the use of a recently established cell-free lysate from tobacco (Nicotiana tabacum L.) BY-2 cells. Using this system, the 130-kDa Cas9 nuclease from Staphylococcus aureus (SaCas9) was produced and subsequently purified via affinity chromatography. The purified apoenzyme was supplemented with ten different sgRNAs, and the nuclease activity was confirmed by the linearization of plasmid DNA containing cloned DNA target sequences.

COVID-19 patients are prone to co-infections during their hospitalization. These co-infections are challenging as they involve longer hospital stays, high costs, and higher mortality risk. Here we present a case of a patient with multi-infection by resistant parasites, fungi, and bacteria during his hospitalization in a Peruvian hospital

Objective: To review a case of acute urticaria, and to explore the links this presentation shares with hyperthyroidism and anti-thyroid medications, along with management strategies for patients presenting with new-onset urticaria and pre-existing thyroid disease. Design: A retrospective case report on a 23-year-old female with hyperthyroidism, on carbimazole therapy.

Populations of ectothermic vertebrates are vulnerable to environmental pollution and climate change because certain chemicals and high temperature can cause sex reversal during their larval development (i.e. genetically female individuals develop male phenotype or vice versa), which may distort population sex ratios. However, we have troublingly little information on sex reversals in natural populations, due to unavailability of genetic sex markers. Here we developed a genetic sexing method based on sex-linked single nucleotide polymorphism loci to study the prevalence and fitness consequences of sex reversal in agile frogs (Rana dalmatina). Out of 125 juveniles raised in laboratory without exposure to sex-reversing stimuli, 6 showed male phenotype but female genotype according to our markers. These individuals exhibited several signs of poor physiological condition, suggesting stress-induced sex reversal and inferior fitness prospects. Among 162 adults from 11 wild populations in North-Central Hungary, 20% of phenotypic males had female genotype according to our markers. These individuals occurred more frequently in areas of anthropogenic land use; this association was attributable to agriculture and less strongly to urban land use. Female-to-male sex-reversed adults had similar body mass as normal males. We recorded no events of male-to-female sex reversal either in the lab or in the wild. These results support recent suspicions that sex reversal is widespread in nature, and suggest that human-induced environmental changes may contribute to its pervasiveness. Furthermore, our findings indicate that sex-reversal is associated with stress and poor health in early life, but sex-reversed individuals surviving to adulthood may participate in breeding.

Hand and foot syndrome (HFS) is a toxic dermatologic reaction to chemotherapy, commonly described with capecitabine, 5fluouracile, vinorelbine, and cytarabine. Taxanes are less likely to induce HFS, and very few cases reported paclitaxel-induced HFS. We report a serious case of HFS induced by paclitaxel in a breast cancer female.