bluuebunny/crossref_metadata_2025 huggingface dataset:
The transformation of isolated gastric myeloid sarcoma into acute myeloid leukemia presenting with a complex karyotype and TLS-ERG gene fusion
Authors: Gao Lu , Xu Yan , Tian Zuguo , Xia Junxiu , Yuan Zhong , Chen Di , Ren Mingqiang
Published: May 2022

Rationale:

Isolated myeloid sarcoma (MS) is characterized by the rapid proliferation of myeloblasts of acute myeloid leukemia (AML), without any blood or bone marrow involvement. This disease can manifest with extramedullary organ involvement, such as the skin, lymph nodes, bone, brain, breast cervix, and visceral organs, while the occurrence of myeloid sarcomas in the stomach is rare. Isolated MS has been associated with acute myeloid leukemia (AML), but the rapid progression of MS to acute myeloid leukemia with a complex karyotype and TLS-ERG fusion gene is even rarer.

Patient concerns:

A 33-year-old woman suffered from persistent epigastric pain accompanied by two months of anorexia and nausea, as well as 1-week of melena.

Diagnosis:

This patient was initially diagnosed with gastric MS that eventually transformed into AML with a complex karyotype and TLS-ERG fusion gene, 4 months later.

Interventions:

Only palliative care, including nutrition support, antacids, blood transfusion, anti-infection methods were used on this patient to determine the cachexia status and the family's requirement.

Outcomes:

Routine follow-up results demonstrated this patient had died due to cerebral hemorrhage five months after the diagnosis of MS.

Lessons:

Comprehensive integration of patient history, imaging features, mass and bone marrow biopsy, and molecular cytogenetic may provide insights that could help us avoid the misdiagnosis of gastric MS. Isolated gastric MS can rapidly progress to AML with a poor prognosis if the patient does not receive appropriate treatment.
Adrenal insufficiency and pregnancy
Authors: Alexandraki Krystallenia I. , Kaltsas Gregory A.
Published: May 2022

Introduction

Adrenal insufficiency is a disorder characterized by the failure of adrenocortical function because of distorted function of hypothalamic–pituitary– adrenal (HPA) axis. Pregnancy is a state of a physiological glucocorticoid excess as the HPA axis is functioning at a higher level.

Purpose of review

The aim of the present review was to shed light on current evidence of adrenal insufficiency management during pregnancy, along with maternal and neonatal outcomes.

Recent findings

A recent multicenter study under the auspices of the European Network for the Study of Adrenal Tumours (ENSAT) presented real-life data of pregnant women with adrenal insufficiency documenting an increased use of hydrocortisone (or mineralocorticoids when needed according to the level of disorder) replacement treatment, increased rates of caesarean section, preterm delivery and adrenal crises along with peripartum and postpartum complications but no maternal or neonatal fatality. These data were in agreement with those obtained from previously published studies.

Conclusion

The limited published evidence is in line with the present guidelines as real-life data did not document any increased fatality among pregnant women or newborns. Prospective data with prolonged follow-up are needed to shed more light on appropriate dose adjustments to avoid the risks of under-replacement or over-replacement of glucocorticoid and/or mineralocorticoid drugs and their sequelae.

A recent multicenter study by ENSAT presented real-life data of pregnant women with adrenal insufficiency documenting an increased use of hydrocortisone as replacement treatment during pregnancy, along with an increased rate of caesarean section and preterm delivery, adrenal crises, peripartum and postpartum complications but no maternal or neonatal fatality. These data are in agreement with those of a previously published study and also confirm the statements made by the recent guidelines. Prospective data are needed aiming to develop precise therapeutic protocols during each trimester of pregnancy according to the different causes of adrenal insufficiency.
Burnout in emergency medicine professionals after 2 years of the COVID-19 pandemic: a threat to the healthcare system?
Authors: Petrino Roberta , Riesgo Luis Garcia-Castrillo , Yilmaz Basak
Published: May 2022

Background

Burnout is a common problem among healthcare professionals (HCPs), in particular young doctors and nurses working in emergency medical services. The coronavirus disease 2019 (COVID-19) pandemic has generated a substantial increase in the workload of those working in front-line services, and there is evidence of physical and mental distress among professionals that may have caused an increase in burnout.

Objective

The objective of the study was to evaluate the level of burnout in the different professionals of emergency medical services.

Design and participants

In January and February 2022, we conducted an online survey based on the Abbreviate Maslach inventory with the addition of three questions focused on possible modifying factors. The survey was disseminated to HCP via the list of European Society for Emergency Medicine contacts.

Outcome measures

The analysis was based on two of the three elements of the Maslach burnout concept, ‘depersonalisation’, ‘emotional exhaustion’, and ‘personal accomplishment’. Overall burnout was defined when at least one of the two elements ‘depersonalisation’ or ‘emotional exhaustion’ reached the level of high burnout.

Results

The number of responders was 1925, 84% of which were physicians, 12% nurses, and 2% paramedics. Burnout was present in 62% of all responders. A high burnout level was reported for depersonalisation, emotional exhaustion, and personal accomplishment in 47%, 46%, and 48% of responders, respectively. Females reported a higher proportion of burnout compared with males 64% vs. 59%, difference −6% [95% confidence interval CI, −8 to −1.9], and nurses higher than physicians, 73% vs. 60%, difference −13 (95% CI, −18.8 to −6). Less experienced professionals reported higher levels of burnout: those with less than 5 years of experience the burnout level was 74% compared with the group with more than 10 years, 60%, difference −26% (95% CI, −32 to −19.5). Reported frequent understaffing situations were associated with a higher risk of burnout: 70% vs. 37%, difference −33% (95% CI, −41 to −25). Burnout was associated with a higher risk of desire to change the workplace: 87% vs. 40%, difference −47% (95% CI, −52 to −42). Survey responders reported having access to support programmes in 41% of cases.

Conclusion

In this study, there is a high reported level of burnout among emergency HCPs. Several risk factors were identified such as being understaffed, female, or having less experience. HCPs with burnout thought more frequently about leaving the workplace, posing a threat to healthcare systems.
FOCAD Indel in a Family With Juvenile Polyposis Syndrome
Authors: MacFarland Suzanne P. , Xie Hongbo , Dent Maiah H. , Greed Bridgid , Plon Sharon E. , Scollon Sarah R. , Brodeur Garrett M. , Howe James R.
Published: May 2022

Juvenile polyposis syndrome (JPS) is a childhood polyposis syndrome with up to a 50% lifetime risk of gastrointestinal cancer. Germline pathogenic variants in BMPR1A and SMAD4 are responsible for around 40% of cases of JPS, but for the majority of individuals, the underlying genetic cause is unknown. We identified a family for which polyposis spanned four generations, and the proband had a clinical diagnosis of JPS. Next-generation sequencing was conducted, followed by Sanger sequencing confirmation. We identified an internal deletion of the FOCAD gene in all family members tested that altered the reading frame and is predicted to be pathogenic. We conclude that inactivation of the FOCAD gene is likely to cause JPS in this family.
A Primary Spinal Nongerminomatous Germ Cell Tumor With Multiple Intracranial Metastases in a Toddler
Authors: Ramanathan Subramaniam , Hill Rebecca M. , Ryles Jade , Halliday Gail , Mitra Dipayan , Bailey Simon
Published: May 2022

Central nervous system germ cell tumors (CNS-GCTs) comprise 4% of all pediatric CNS tumors, with one third being nongerminomatous GCT (CNS-NG-GCT) type. The majority of these tumors arise in the intracranial compartment with 20% having drop metastases in the spine. We present a rare case of a 2-year-old boy with a primary intradural-extramedullary NG-GCT arising from the lumbosacral spine with a trifecta of unfavorable features, that is, young age, alpha-feto protein >1000 ng/mL, and disseminated disease within the cranium. Owing to his young age, he was treated with chemotherapy alone, avoiding radiation. His tumor marker (alpha-feto protein) declined from 8468 to 10 k-U/L over 8 weeks, and he remained in remission at the last follow-up. This atypical presentation of an intradural-extramedullary tumor with cranial dissemination in a childhood NG-GCT has yet to be described in the literature. Here we use this opportunity to highlight the treatment strategies and challenges in this unique clinical case.
Effects of Protein and Amino Acid Supplementation on Muscle Mass and Strength in a Healthy Population
Authors: Jibril Aliyu Tijani , Jayedi Ahmad , Ghorbaninejad Parivash , Mohammadpour Saba , Djafarian Kurosh , Clark Cain C. T. , Shab-Bidar Sakineh
Published: May 2022

The objective of this study was to investigate the effect of protein and/or amino acid supplementation on muscle mass and strength in a healthy population. A structured literature search was conducted from database inception up to October 23, 2019, using PubMed and Scopus. Data were collected from randomized controlled trials and weighted mean difference, and its 95% confidence interval was calculated by using a random-effects model. Risk of bias was assessed using the Cochrane tool. Data were included from 46 randomized controlled trials, totaling 2049 participants. Protein but not amino acid supplementation resulted in significant positive effects on muscle mass (weighted mean difference, 0.47 kg; 95% confidence interval, 0.18-0.75 kg; P < .001) and upper body strength. The significant effect of protein supplementation on muscle mass persisted in the subgroups with and without resistance training, in young (<30 years) and older (≥59 years) adults, and across either gender. This review suggests that dietary protein and/or amino acid supplementation may promote muscle mass hypertrophy and/or maintenance, as well as some measures of muscular strength in a healthy population.
Brief Report: Impact of Antiretroviral Regimen on Pregnancy and Infant Outcomes in Women With HIV/ HBV Coinfection
Authors: Kiweewa Flavia Matovu , Tierney Camlin , Butler Kevin , Peters Marion G. , Vhembo Tichaona , Moodley Dhayendre , Govender Vani , Mohtashemi Neaka , Ship Hannah , Musoke Philippa , Dula Dingase , George Kathy , Chakhtoura Nahida , Fowler Mary G. , Currier Judith S. , Bhattacharya Debika
Published: May 2022

Background:

There are limited data on the impact of antenatal antiretroviral regimens (ARV) on pregnancy and infant outcomes in HIV/HBV coinfection. We compared outcomes among 3 antenatal antiretroviral regimens for pregnant women with HIV/HBV.

Methods:

The PROMISE study enrolled ARV-naive pregnant women with HIV. Women with HBV were randomized to (no anti-HBV)-zidovudine (ZDV) + intrapartum nevirapine and 1 week of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC); (3TC)-3TC + ZDV + LPV/r; or (FTC-TDF)-FTC + TDF + LPV/r. Pairwise group comparisons were performed with Fisher exact, t, or log rank tests. Adverse pregnancy outcome (APO) was a composite of low birth weight, preterm delivery, spontaneous abortion, stillbirth, or congenital anomaly.

Results:

Of 138 women with HIV/HBV, 42, 48, and 48 were analyzed in the no anti-HBV, 3TC, and FTC-TDF arms. Median age was 27 years. APOs trended lower in the no anti-HBV (26%) vs 3TC (38%), and FTC-TDF arms (35%), P ≥ 0.25). More infant deaths occurred among the FTC-TDF [6 (13%)] vs no anti-HBV [2 (5%)] and 3TC [3 (7%)] arms. There were no differences in time-to-death, HIV-free survival, birth or one-year WHO Z-score length-for-age, and head circumference. Hepatitis B e antigen (HBeAg) was associated with an increased risk of APO, 48% vs 27% (odds ratio 2.79, 95% confidence interval: 1.19 to 6.67, post hoc).

Conclusion:

With HBV/HIV coinfection, the risk of an APO was increased with maternal ARV compared with ZDV alone, although the differences were not statistically significant. Maternal HBeAg was associated with a significantly increased risk of APO. Infant mortality was highest with FTC + TDF + LPV/r. Early assessment of HBeAg could assist in identifying high-risk pregnancies for close monitoring.
Diffuse Bone Marrow Involvement of Multiple Myeloma on [18F]PSMA-1007 PET/CT
Authors: Michalski Kerstin , Jilg Cordula A. , Engelhardt Monika , Meyer Philipp T. , Ruf Juri
Published: May 2022

A 71-year-old man presented with chronic anemia (hemoglobin 7.3 g/dL). Further serum analyses showed elevated prostate-specific antigen (13 ng/mL), suggestive of prostate cancer. However, ultrasound-guided transrectal sextant biopsy did not find any evidence of prostate cancer. In order to improve guidance of intended repeated biopsy, [18F]prostate-specific membrane antigen (PSMA) 1007 PET/CT was performed, which showed a solitary lesion with strong PSMA expression in the left peripheral zone in the prostate gland. Surprisingly, also a diffuse bone marrow involvement with predominantly osteolytic lesions was observed. This massive osseous tumor burden was clearly discordant to the only relatively mild elevated prostate-specific antigen. The subsequent bone biopsy revealed multiple myeloma. This case does not only highlight a possible pitfall on PSMA PET/CT, but also raises the question on how far PSMA ligands may offer diagnostic and therapeutic potential in multiple myeloma.
Tracheitis Diagnosed With 68Ga-PSMA PET/CT in a Patient With COVID-19
Authors: Aksu Ayşegül , Bozkurt Kübra , Yılmaz Burçak
Published: May 2022

A 57-year-old man with newly diagnosed with prostate cancer was admitted to our department for 68Ga–prostate-specific membrane antigen PET/CT imaging. The patient, who was asymptomatic at the time of imaging, had increased diffuse 68Ga–prostate-specific membrane antigen uptake in the trachea on PET/CT. No ground-glass density suggestive of pneumonia in both lungs was observed. The patient, whose symptoms developed 2 days after PET/CT imaging, was diagnosed with coronavirus disease 2019 by real-time polymerase chain reaction.
Incidental Detection of Radiotracer Uptake in Spindle Cell Lipoma on 18F-PSMA PET/CT
Authors: Hod Nir , Sherf Yehonatan , Lantsberg Sophie
Published: May 2022

An 84-year-old man underwent 18F–prostate-specific membrane antigen (PSMA) PET/CT for staging of a newly diagnosed prostate adenocarcinoma. PET/CT revealed high 18F-PSMA uptake in a thigh mass, which was initially suspected for a metastasis. Histopathology revealed a rare entity of spindle cell lipoma, which should be added to the reported list of neoplasms that can show “false-positive” PSMA uptake during evaluation of patients with prostate carcinoma representing a potential interpretative pitfall.
Renal Pelvis Immunoglobulin G4–Related Disease Mimicking Malignant Tumor
Authors: Zhang Zeyu , Liu Yanfang , Zhang Lu , Cheng Chao , Zuo Changjing
Published: May 2022

A space-occupying lesion in the left renal pelvis was found in a 56-year-old man. The patient voluntarily participated in a clinical trial of 68Ga-FAPI in solid tumors. PET/CT images revealed an intense 18F-FDG and 68Ga-FAPI uptake in this lesion. Malignant tumor was suspected. The patient subsequently underwent laparoscopic partial nephrectomy. The postoperative pathological examination established the diagnosis of immunoglobulin G4–related disease.
Unusual Metastatic Prostate Cancer in Subcarinal Lymph Node and Peritoneal Nodule Found on 18F-PSMA PET/CT With Rising PSA of 0.4 ng/mL
Authors: Gao Mamie , Lu Yang
Published: May 2022

A 79-year-old man with metastatic prostate cancer underwent radical prostatectomy and bilateral lymph node dissection and received multiple lines of systematic treatment for his biopsy-proven peritoneal carcinomatosis. During the disease course, his prostate-specific antigen rose from 0.1 ng/mL to 0.4 ng/mL in 4 months, and testosterone level was <3 ng/dL. Workup 18F-DCFPyL PET/CT showed unusual prostate-specific membrane antigen–avid, 1.1-cm subcarinal lymph node and a 0.8-cm peritoneal nodule, which were not hypermetabolic on an 18F-FDG PET/CT 6 days later. This case illustrated the sensitivity for 18F-DCFPyL PET/CT in detecting metastatic castration-resistant prostate cancer.
A Rare Extramedullary Involvement Site in Patients With Multiple Myeloma
Authors: Gülbahar Ateş Seda , Uçmak Gülin
Published: May 2022

Multiple myeloma (MM) is a hematologic malignancy associated with uncontrolled clonal proliferation of plasma cells. Extramedullary disease in MM is an aggressive entity with a poor prognosis. Moreover, involvement of the gastrointestinal tract is a rare aggressive biological sign. 18F-FDG PET/CT is an irreplaceable modality in the assessment of extramedullary disease. We present 2 cases with gastric involvement of MM that were shown by 18F-FDG PET/CT and confirmed as plasma cell infiltration pathologically. 18F-FDG PET/CT studies of MM patients should be interpreted carefully for gastrointestinal involvement, and it should be kept in mind that it can mimic other malignancies.
E2027 Cardiac Safety Evaluation With Concentration-Response Modeling of ECG Data to Inform Dose Selection in Studies in Patients With Dementia With Lewy Bodies
Authors: Landry Ishani S. , Boyd Peter , Aluri Jagadeesh , Darpo Borje , Xue Hongqi , Brown Randy , Reyderman Larisa , Lai Robert
Published: May 2022

Background:

E2027 is a novel, highly selective and potent inhibitor of phosphodiesterase 9 in development for dementia with Lewy bodies. Cardiac safety assessments for emerging agents are essential to avoid drug-induced QT interval prolongation, which may predispose individuals to potentially fatal ventricular arrhythmias. To evaluate the cardiac safety of E2027 and to inform dose selection for the phase 2 study of E2027 in dementia with Lewy bodies, we evaluated concentration-response modeling of pooled electrocardiogram data.

Patients and Methods:

A post hoc concentration-QTc analysis evaluated potential QT effects using data from 2 randomized, double-blind studies in healthy subjects: a single ascending dose (SAD) study and a multiple ascending dose (MAD) study. Daily E2027 doses ranged from 5 to 1200 mg.

Results:

A linear mixed-effects model was used to establish the relationship between plasma concentrations of E2027 and change from the baseline of QTcF (ΔQTcF). A significant but shallow relationship was observed in the estimated slope of the concentration-ΔQTcF: 0.002 ms/ng/mL (90% confidence interval: 0.0007-0.0031) with a small, nonsignificant treatment effect-specific intercept of −0.6 ms. Based on this pooled concentration-QTc analysis, an effect on the QTcF interval >10 ms can be excluded up to E2027 plasma concentrations of ∼3579 ng/mL, corresponding to a dose at least 4-fold larger than the 50 mg phase 2 dose.

Conclusion:

This pooled post hoc analysis evaluating cardiac safety of E2027 demonstrated that clinically concerning QTcF prolongation and related cardiac complications are highly unlikely with proposed E2027 doses planned for phase 2.
Duloxetine alleviates oxaliplatin-induced peripheral neuropathy by regulating p53-mediated apoptosis
Authors: Wang Man , Zhang Ling , Liu Xiaoli , Qiu Siyan , Xu Rong , Yang Chao , Lu Yuting , Zhang Peng , Yan Ming , Zhu Jing
Published: May 2022

Oxaliplatin (OXA) is a key platinum-based chemotherapeutic agent for treatment of metastatic colorectal cancer, but the side effects of acute and chronic neuropathies limit its clinical application. Duloxetine has been found to have the potential to prevent OXA-induced peripheral neuropathy in several studies, but the underlying mechanisms remain unclear. The purpose of this study was to evaluate the effects of duloxetine on OXA-induced peripheral neuropathy and to find the potential mechanisms. The neuropathic pain mice model was used to explore the role of duloxetine on OXA-induced peripheral neuropathy by measuring the change of thermal withdrawal latency (TWL), paw withdrawal threshold (PWT), and intraepidermal nerve fiber density (IENFD). Moreover, to explore molecular mechanisms, effects of duloxetine on OXA-induced changes in mRNA and protein expression of components of the p53-related pathways in cultured rat dorsal root ganglion (DRG) neurons were measured. In vivo, we found duloxetine treatment could significantly prevent the changes in the TWL, PWT to mechanical stimulation, and the IENFD of mice caused by OXA. In vitro, we found duloxetine notably inhibits the relative mRNA and protein expression levels of p53, Bax/Bcl2, caspase-3, and caspase-9 in DRG neurons, which may indicate duloxetine protected the DRG neuron by inhibiting p53-related pathways. These results suggest that duloxetine could alleviate the OXA-induced peripheral neuropathy. Duloxetine deserves further consideration as a potential protective agent against peripheral neuropathy.
Electroconvulsive Treatment Utilization for Inpatient Management of Catatonia in Adolescents With Schizophrenia Spectrum Disorders
Authors: Patel Rikinkumar S. , Hobart Kelsey , Wadhawan Abhishek , Chalia Ankit , Youssef Nagy A.
Published: May 2022

Objective

The aim of this study was to determine rates of electroconvulsive therapy (ECT) use for catatonia in schizophrenia spectrum disorders, stratified by patient demographics and hospital characteristics, and its impact on inpatient length of stay and cost.

Methods

We found 155 adolescents (aged 12–18 years) with principal discharge diagnosis of schizophrenia spectrum disorders with catatonia from the National Inpatient Sample. They were subgrouped into ECT (n = 20) and non-ECT (n = 135) groups. We used descriptive statistics to evaluate the utilization of ECT for catatonia and independent-sample t test for continuous variables with statistical significance at P ≤ 0.05.

Results

The overall utilization rate of ECT in adolescents for catatonia was 12.9%. A high rate of ECT use was evident for Whites (30.8%) compared with the other race/ethnicities and also was seen in private health insurance beneficiaries (20%). The rate of ECT use varied by the region, with highest for the Northeast (20%), followed by the South (18.2%), and the West (14.3%). Adolescent inpatients with catatonia in public and teaching type, and large bed-size hospitals were more likely to receive ECT than their counterparts. The mean number of ECT sessions required during the inpatient stay was 5.2 (range, 1–15), and the mean number of days from admission to initial ECT was 2.5 (range, 0–6).

Conclusions

Electroconvulsive therapy is used for approximately only 13% of adolescents with catatonia when comorbid schizophrenia spectrum disorders are present, suggesting that many patients may not get evidence-based treatment. Future studies in this area are needed.
Cerebral venous sinus thrombosis as a complication of cranial melioidosis – a rare case report
Authors: Bahuleyan Biji , Adarsh Manuel , Akarsh Jayachandran , M. L. Arun Kumar , Rohitha Chandra S. , Elenjickal George Xavier , T. V. Sreevalsan , Thomas Santhosh George
Published: May 2022

Cerebral venous sinus thrombosis is a rare complication of cranial melioidosis. We report a case of an adult male who presented with skull osteomyelitis, transverse sinus thrombosis and multiple brain abscesses. His blood cultures grew

Burkholderia pseudomallei

. The patient finally succumbed after multiple recurrences of the infection despite surgical excision of the osteomyelitic bone and the recommended antibiotic treatment. The management of cerebral venous sinus thrombosis in patients with cranial melioidosis is discussed along with a brief review of the literature.
Mobile antimicrobial resistance in Neisseria gonorrhoeae
Authors: Cehovin Ana , Jolley Keith A , Maiden Martin CJ , Harrison Odile B , Tang Christoph M
Published: May 2022

Neisseria gonorrhoeae (the gonococcus) is the causative agent of the sexually-transmitted infection gonorrhoea, and has developed resistance to all classes of antimicrobials. In gonococci, plasmids can mediate high-level antimicrobial resistance (AMR) to tetracyclines and ß-lactams. Plasmids can spread through bacterial populations by transformation and conjugation, resulting in the rapid dissemination of traits. Characterisation of plasmids, including understanding their distribution in bacterial populations, is therefore key to understanding bacterial evolution, and in particular the spread of AMR. N. gonorrhoeae can harbour three plasmids, conjugative (pConj), ß-lactamase (pbla) and cryptic (pCryp). Using genomic and phylogenetic analyses, we show that plasmids are widespread in a large collection of gonococcal isolates from 56 countries. We found that variants of pConj (which can mediate tetracycline resistance) and pbla expressing TEM-135 ß-lactamase are associated with distinct gonococcal lineages. Furthermore, AMR plasmids are significantly more prevalent in gonococci from less wealthy countries. Over 94% of gonococci possess the cryptic plasmid (pCryp), and its absence can be correlated with the presence of a novel chromosomal Type IV secretion system. Our results reveal the extent of plasmid-mediated AMR in the gonococcus, particularly in less wealthy countries, where diagnostic and therapeutic options can be limited, and highlight the risk of their global spread.
Host environment induces daptomycin tolerance in Staphylococcus aureus
Authors: Ledger Elizabeth , Reichmann Nathalie , Grundling Angelika , Edwards Andrew
Published: May 2022

Daptomycin is a last-resort antibiotic for the treatment of invasive diseases caused by methicillin-resistant Staphylococcus aureus. However, despite potent activity in vitro,daptomycin fails to resolve up to 30% of cases of staphylococcal bacteraemia, suggesting that the host environment reduces bacterial susceptibility to the antibiotic. Using human serum as a model of bacteraemia, we demonstrated that the host environment induced daptomycin tolerance via activation of the GraRS two-component system. Testing of various antimicrobial peptides present in serum revealed that the human cathelicidin LL-37 was able to bind GraS, induce GraRS signalling and confer daptomycin tolerance. Activation of GraRS by serum led to daptomycin tolerance via changes in the staphylococcal cell envelope. For example, GraRS-dependent increases in positive surface charge and peptidoglycan content occurred in serum, leading to reduced daptomycin binding. Additionally, incubation in serum led to a Cls2-dependent increase in the cardiolipin content of the membrane which contributed to daptomycin tolerance. Finally, inhibition of both peptidoglycan and cardiolipin synthesis together completely abolished acquisition of daptomycin tolerance in serum, demonstrating that these processes fully explain the tolerance phenotype. In summary, host LL-37 activates staphylococcal GraRS signalling, causing changes in the cell surface which confer daptomycin tolerance. This demonstrates how host defences can compromise antibiotic efficacy, and also provides a rationale for combination therapies to prevent the development of daptomycin tolerance and reduce rates of treatment failure.
Evaluation of essential oils efficacy on antibiotic-resistant Salmonella strains
Authors: Masotti Chiara , Battistini Roberta , Listorti Valeria , Razzuoli Elisabetta , Tramuta Clara , Decastelli Lucia , Ercolini Carlo , Serracca Laura
Published: May 2022

Background

The emergence of multidrug resistant (MDR) pathogens has drawn attention to natural antimicrobial compounds, such as essential oils (EOs)

Methods

The aim of the present study was to investigate the inhibitory activity of three EOs against 15 Salmonella strains resistant to 16 commonly used antimicrobials. EOs of O. vulgare, T. serpyllum, and T. vulgariswere tested in triplicate for 15 bacterial strain by Kirby-Bauer disk diffusion method and broth microdilution method to determine the minimal inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC), according to the Clinical and Laboratory Standards Institute guidelines with minor modifications.

Results

O. vulgare and T. serpyllum showed high antimicrobial activity compared to T. vulgaris in all tested antibiotic-resistant strains (P-value <0.01). The mean diameter of the bacterial growth inhibition zone was 18.7 mm for O. vulgaris, 19.2 mm for T. serpyllum, and 14.2 mm for T. vulgaris. The MIC and MBC mean values of O. vulgare were respectively 0.037% and 0.058%, for T. serpyllum 0.036% and 0.041%, for T. vulgaris 0.13% and 0.15%. All strains resulted resistant totrimethoprim-sulamethoxazoleand 14 strains resulted resistant to tetracycline, considered a highly important antimicrobial. Among Salmonella serovars tested the monophasic S. Typhimurium has exhibited the highest antimicrobial resistance to synthetic molecules while they were sensitive to EOs.

Conclusions

The EOs of O. vulgare and T. serpyllum, which contain carvacrol as the main constituent, showed the greatest antimicrobial effect against MDR Salmonella strains.
Trans-cinnamaldehyde - geraniol mixture – antibacterial activity and haemotoxicity
Authors: Olkiewicz Daria , Walczak Maciej , Stepczyńska Magdalena
Published: May 2022

The aim of this study was to test the antibacterial activity and haemotoxicity of (trans)-cinnamaldehyde and geraniol. Conducted analyzes showed that (trans)-cinnamaldehyde-geraniol mixture have antibacterial properties against S. aureus ATCC6538, E. coli ATCC8739 and P. aeruginosa KKP991. MIC and MBC of the mixture was determined for each strain. For S. aureus MIC=0.065 mg/ml, MBC=1.25 mg/ml, for E. coli MIC= 0.5 mg/ml, MBC=1 mg/ml and for P. aeruginosa MIC=0.5 mg/ml, MBC=1.25 mg/ml. Also the blood compatibility test was done, and it showed that MIC for S. aureus (0.025 mg/ml) is non-haemotoxic, but other MICs and all MBCs, unfortunately are.
Evaluation of a monoglyceride for antimicrobial activity against Gram-positive and -negative bacteria
Authors: Ukachukwu Faith , Alany Raid , Snyder Lori
Published: May 2022

Background

The Gram-positive bacterium Staphylococcus aureus, and Gram-negative Neisseria gonorrhoeae and Pseudomonas aeruginosa bacteria, have developed multi-drug resistance to currently recommended antibiotic treatment resulting in worse clinical outcomes and significant economic burden. N. gonorrhoeae causes the sexually transmitted infection gonorrhoea and S. aureus and P. aeruginosa causes nosocomial infections including a plethora of infections that affect the skin, lungs, heart, eyes, ears, bones, and blood. Novel therapies are desperately needed to replenish the clinical pipeline as current antibiotic treatments fail.

Methods

Monolaurin was investigated against strains of N. gonorrhoeae, S. aureus and P. aeruginosa. The minimum inhibitory concentration of monolaurin was determined by agar diffusion assay for N. gonorrhoeae and broth microdilution assay for S. aureus and P. aeruginosa. Bactericidal activity of monolaurin was assessed in log reduction assay and the time - kill activity of various concentrations of the monoglyceride was evaluated over 5 hours. At least 4 log10 killing activity was considered bactericidal.

Result

Monolaurin inhibited growth ofS. aureus, N. gonorrhoeae, and P. aeruginosa at a range of 0.1mM - 3.13mM concentrations. At 1.5mM concentration, monolaurin killed S. aureus and N. gonorrhoeae at 180 minutes and 60 minutes, respectively. Monolaurin at 3mM concentration rapidly killed N. gonorrhoeae within 2 minutes while 25mM concentration killed P. aeruginosa within 60 minutes.

Conclusion

The evidence suggests that monolaurin actively killed Gram-positive and remarkably Gram-negative bacteria. This monoglyceride can potentially be developed as an antimicrobial therapy against these bacterial infections and may prove useful when coinfection with P. aeruginosa and S. aureus are present.
Host mediated microbiome selection to study the changes in the nutrient cycling, root exudation and microbial population in the rhizosphere of soybean genotypes
Authors: Haridas Deepa Manikkath
Published: May 2022

The study was conducted with an aim to understand the changes in soil enzyme activity in the plant rhizosphere during host mediated selection of rhizosphere microbiome. Soil samples were collected from three different locations on a farm in the Reading area, UK. Two popular genotypes of Soybean (Glycine max) were chosen for the study, Kenchen and Siverka. Initial microbiome inoculum was prepared by mixing field soil with sterilized water and this was added to the autoclaved coir: sand mix. After four weeks of plant growth, plants were uprooted from the soil, rhizosphere soil collected for soil enzyme estimation and NGS analysis. Root exudates were collected and stored in freezer for analysis.

Growth of plants in legume soils was significantly higher. The plants in legume soil produced nodules which confirmed the presence of rhizobia in these soils. Independent analysis within each soil type showed that, the interaction between soil type and genotype is very significant with respect to enzyme activity. The presence of microbiome along with plants had a significant effect on enzymatic activity. GCMS analysis of root exudates from plants in each soil showed variations in individual chromatograms. The difference in enzyme activity with plant growth shows that there are changes taking place in the soil. Further in this study, NGS analysis of rhizosphere soil will shed more light into the changes happening in the soil microbiome and if the changes are related to the enzymatic changes and plant root exudation.
Investigating the microbiological risks associated with urban flooding in the UK
Authors: Scutt Sophie , Shucksmith James , Douterelo Isabel
Published: May 2022

Over the last 30 years, the frequency and occurrence of intense rainfall, and thus extreme hydrological events –flooding- has steadily increased. Drainage infrastructure in the UK was not designed for a changing climate, and many sewer systems in densely populated urban areas, are unable to cope. Sewage overflow and surface run off in urban areas can act as vectors for the dissemination of pathogens, known to cause disease among human populations. Most of the previous studies in this field have focused on using faecal indicators such as E.coli when assessing the public health risk of floodwater [1]. However, traditional indicators do not accurately reflect the true risk that urban flooding poses [2]. Little is understood in regards to the survivability and behaviour of pathogens in different urban settings, which are fundamental to determine potential risks to public health.

Previous investigations in UK waterlogged soils have shown a clear response of microbial communities to water table variation, temperature, and nutrient availability in soil profiles [3]. This research aims to investigate, using advanced molecular methods, the dynamics of pathogens (i.e. movement through soil and survival rates), and microbial interactions at the soil/water interface- collecting information from field work studies and laboratory-controlled experiments.

The outcomes from this research will inform future management strategies of flooded sites that will aid to protect public health.

References

[1] Yard et al., 2014. J. Environ. Sci. Health 49, 1236-1243.

[2] Hussain, 2019. Freshwater Microbiology 10, 393-420.

[3] Douterelo et al., 2009. Int. Biodeterior. Biodegradation 63, 6, 795-805.
Meteorites: beneficial or toxic for life on Early Earth? Growth of an anaerobic microbial community on a carbonaceous chondrite
Authors: Waajen Annemiek C. , Prescott R. , Cockell Charles S.
Published: May 2022

Meteoritic material accumulated on the surface of the anoxic Early Earth during the Late Heavy Bombardment around 4.0 Gya. These meteorites may have provided the Earth with extra-terrestrial nutrients and energy sources for early life. How could the presence of meteorites have affected the origin and evolution of early life on Earth? And what is the influence of geothermal activity on the Earth’s surface? This research investigates the growth of an anaerobic microbial community from pond sediment on non-pyrolyzed (pristine) or pyrolyzed (heat-treated) carbonaceous chondrite ‘Cold Bokkeveld’. A microbial community was grown anaerobically in batch cultures containing a liquid environment and powdered non-pyrolyzed or pyrolyzed Cold Bokkeveld. Cell concentrations were measured by Colony-Forming Units on agar plates. The community composition in the presence of non-pyrolyzed meteorite was determined by 16S rRNA amplicon sequencing. Non-pyrolyzed Cold Bokkeveld supported the growth of a stable, anaerobic community containing mainly the Deltaproteobacteria Geobacteraceae and Desulfuromonadaceae. Members of these families are known to use elemental sulfur and ferric iron as electron acceptors, and organic compounds as electron donors. Pyrolyzed Cold Bokkeveld however, was inhibitory to the growth of the microbial community. These results show that carbonaceous chondrites can host an anaerobic microbial community, but that pyrolysis, e.g. by geothermal activity, can inhibit microbial growth and potentially toxify the material. This indicates that extraterrestrial meteoritic material and the environment on Early Earth could have shaped the nature of early microbial ecosystems by enhancing growth of microorganisms with metabolic capabilities favored in the presence of this material.
Different molecular routes to mat formation in environmental Pseudomonas isolates
Authors: Mukherjee Anuradha , Gallie Jenna
Published: May 2022

Many bacterial species secrete polymers and form mat-like structures. These mats can be useful (e.g., in bioremediation), or problematic (e.g., in hospital settings). The molecular bases of mat formation have been investigated in a number of species, including various pseudomonads. One well-characterized example is the plant symbiont Pseudomonas fluorescens SBW25. Laboratory populations of SBW25 readily acquire mutations in one of three regulatory loci (wsp, aws, mws), leading to the over-production of the secondary messenger cyclic-di-GMP. In turn, this activates the production of a cellulose-like polymer, the major structural component of the SBW25 mat. Here, we dissect and compare the molecular mechanisms of mat formation in two further plant-associated pseudomonads: P. simiae PICF7 and P. fluorescens A506. We find that both PICF7 and A506 are capable of mat formation in the laboratory, by distinct molecular routes. Mat formation in PICF7 involves mutations in wsp, aws, or mws that serve to activate the production of Pel (as opposed to cellulose in SBW25). Contrastingly, A506 mat formation does not require mutation of wsp, aws, or mws (despite their retention in the genome). Instead, our results are consistent with a readily reversible, non-mutational route to polymer production and mat formation in A506. Overall, our results demonstrate the presence of multiple molecular routes to mat formation among environmental, plant-associated pseudomonads.

The presented work has since been published: Mukherjee A, Dechow-Seligmann G, Gallie J. 2022. Molecular Microbiology 117(2): 394-410.
Whole genome sequencing and comparative analysis of a novel Chlamydia psittaci strain
Authors: Livingstone Morag , Ribeca Paolo , Beeckman Delphine , Ende Arie van der , Pannekoek Yvonne , Vanrompay Daisy , Longbottom David
Published: May 2022

Background

Chlamydia abortus and Chlamydia psittaci are important pathogens of livestock and avian species, respectively. While C. abortus is recognized as descended from C. psittaci species, there is emerging evidence of strains that are intermediary, including C. psittaci strain 84/2334 that was isolated from a parrot.

Methods

Strain 84/2334 was analysed by multi-locus sequence typing of seven housekeeping genes and by analysis of five species-discriminant proteins. The strain was de novo sequenced for comparison with representative strains from chlamydial species. 16S rRNA and whole genome phylogenetic analyses, network and recombination analyses, and analyses of key virulence-associated genes were conducted to explore its evolutionary relationship with both C. psittaci and C. abortus.

Results

Typing, 16S rRNA and whole genome phylogenetic analyses, as well as network and recombination analyses showed that strain 84/2334 clusters closely with C. abortus. Analyses also suggested a closer evolutionary relationship with classical C. abortus strains, than to two other avian C. abortus or C. psittaci strains. Analyses of virulence-associated genes that exhibit greatest diversity within chlamydial species, reveal greater diversity than present in sequenced C. abortus genomes. The strain also possesses an extrachromosomal plasmid, as found in C. psittaci species but absent from all sequenced classical C. abortus strains.

Conclusion

The results are consistent with 84/2334 being a C. abortus ancestral strain, suggesting that it should be reclassified as C. abortus. The identification of a C. abortus strain bearing an extra-chromosomal plasmid has implications for plasmid-based transformation studies providing a potential route for future vaccine development.
genomeRxiv: a microbial whole-genome database and diagnostic marker design resource for classification, identification, and data sharing
Authors: Pritchard Leighton , Sharma Parul , Mazloom Reza , Pierce Tessa , Irber Luiz , Harrington Bailey , Heath Lenwood , Brown C Titus , Vinatzer Boris
Published: May 2022

genomeRxiv is a newly-funded US-UK collaboration to provide a public, web-accessible database of public genome sequences, accurately catalogued and classified by whole-genome similarity independent of their taxonomic affiliation. Our goal is to supply the basic and applied research community with rapid, precise and accurate identification of unknown isolates based on genome sequence alone, and with molecular tools for environmental analysis.

The DNA sequencing revolution enabled the use of cultured and uncultured microorganism genomes for fast and precise identification. However, precise identification is impossible without

1. reference databases that precisely circumscribe classes of microorganisms, and label these with their uniquely-shared characteristics

2. fast algorithms that can handle the volumes of genome data

Our approach integrates the highly-resolved classification framework of Life Identification Numbers (LINs) with the speed and computational efficiency of sourmash and k-mer hashing algorithms, and the precision and filtering of average nucleotide identity (ANI). We aim to construct a single genome-based indexing scheme that extends from phylum to strain, enabling the unique and consistent placement of any sequenced prokaryote genome.

genomeRxiv includes protocols for confidentiality, allowing groups to identify and announce the identities of newly-sequenced organisms without sharing genome data directly. This protects communities working with commercially- and ethically-sensitive organisms (e.g. production engineering strains, potential bioweapons, and to enable benefit sharing with indigenous communities).

genomeRxiv will also provide online capability to design molecular diagnostic tools for metabarcoding and qPCR, to enable tracking of specific groupings of bacteria directly in the environment.
K1 Escherichia coli form foci in the brain at 24h post infection
Authors: Jasiunaite Zydrune , Hames Ryan , Tang Shiying , Pizza Mariagrazia , Oggioni Marco R.
Published: May 2022

K1 capsule type Escherichia coli is the predominant cause of neonatal meningitis. In an intravenous (IV) infection model with a clinical K1 isolate IHE 3034 adult mice die of sepsis within 24 hours. However, by utilising cefazolin, a first-generation cephalosporin known for its inability to pass through the blood brain barrier, it is possible to prevent bacteraemia and study the early phases of E. coli meningitis in the brain. Mice were infected IV with E. coli IHE 3034 and treated with cefazolin at 12 and 24h intraperitoneal to ensure the survival of animals to the determined end points. The results of the experiment show IHE 3034 is present in the brain as early as 12h and it remains in the tissue 72h post infection even if blood is clear. Despite this, at the cellular level, clear foci formation can be observed in the meninges and the choroid plexus around the vascular endothelial cells at 48h, showing IHE 3034’s ability for intracellular replication inside the meningeal region The foci do not appear to be present at 24 or 72h, indicating for a secondary replication site around the major vascular endothelia sites of the brain. This further promotes the bacterial load increase through cell bursting in the tissue with or without a sustained bacterial influx from the blood. These findings show that K1 E. coli can form foci in the brain which may lead to escalated disease progression and severe morbidity following an initially successful clearance of bloodborne bacteria during sepsis.
Comparison of the Antimicrobial Efficacy and Germicidal Efficiency of 405-nm Light for Surface Decontamination
Authors: Sinclair Lucy , MacGregor Scott , Maclean Michelle
Published: May 2022

Background

The persistence of infectious organisms on hospital surfaces presents a significant challenge to healthcare environments. Low irradiance visible 405-nm light has recently been developed as a method for environmental decontamination, with studies demonstrating successful reductions of environmental bacteria in wards and operating theatres. This study investigates the antimicrobial efficacy of 405-nm light for decontamination of surfaces, and how the dose-response kinetics are affected by use of differing light irradiances.

Methods

Surface-seeded Staphylococcus aureus and Pseudomonas aeruginosa (selected as model Gram-positive and Gram-negative species) were exposed to increasing doses of 405-nm light (≤ 90 Jcm-2) at three discrete irradiances (0.5, 5 and 50 mWcm-2). For both species, inactivation kinetics at each respective irradiance was established and susceptibility at equivalent light doses compared.

Results

Results demonstrate increased bacterial susceptibility to 405-nm light inactivation when exposed at lower irradiance treatments. For both species, 3 Jcm-2 was required when exposed using 0.5 mWcm-2 irradiance to achieve significant bacterial inactivation (P < 0.05; 26.7-73.7% reduction). When exposed at 5 mWcm-2, double the energy (6 Jcm-2) was required to achieve similar reductions. Exposure at the highest irradiance (50 mWcm-2) required 3-5 times greater dose (9-15 Jcm-2) to achieve similar reductions to the lowest irradiance tested (0.5 mWcm-2).

Conclusion

This study provides evidence of the enhanced germicidal efficiency of low irradiance 405-nm light, highlighting its efficacy for continuous environmental decontamination applications. Further investigation into the photo-chemical inactivation mechanisms will be crucial for its optimisation for a range of infection control applications.