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BioRxiv : the Preprint Server For... Jun 2024Group B (GBS) asymptomatically colonizes the vagina but can opportunistically ascend to the uterus and be transmitted vertically during pregnancy, resulting in neonatal...
UNLABELLED
Group B (GBS) asymptomatically colonizes the vagina but can opportunistically ascend to the uterus and be transmitted vertically during pregnancy, resulting in neonatal pneumonia, bacteremia and meningitis. GBS is a leading etiologic agent of neonatal infection and understanding the mechanisms by which GBS persists within the polymicrobial female genital mucosa has potential to mitigate subsequent transmission and disease. Type VIIb secretion systems (T7SSb) are encoded by Firmicutes and often mediate interbacterial competition using LXG toxins that contain conserved N-termini important for secretion and variable C-terminal toxin domains that confer diverse biochemical activities. Our recent work characterized a role for the GBS T7SSb in vaginal colonization and ascending infection but the mechanisms by which the T7SSb promotes GBS persistence in this polymicrobial niche remain unknown. Herein, we investigate the GBS T7SS in interbacterial competition and GBS niche establishment in the female genital tract. We demonstrate GBS T7SS-dependent inhibition of mucosal pathobiont both using predator-prey assays and in the murine genital tract and found that a GBS LXG protein encoded within the T7SS locus (herein named group B streptococcal L XG T oxin A ) that contributes to these phenotypes. We identify BltA as a T7SS substrate that is toxic to and upon induction of expression along with associated chaperones. Finally, we show that BltA and its chaperones contribute to GBS vaginal colonization. Altogether, these data reveal a role for a novel T7b-secreted toxin in GBS mucosal persistence and competition.
IMPORTANCE
Competition between neighboring, non-kin bacteria is essential for microbial niche establishment in mucosal environments. Gram-positive bacteria encoding T7SSb have been shown to engage in competition through export of LXG-motif containing toxins, but these have not been characterized in group B (GBS), an opportunistic colonizer of the polymicrobial female genital tract. Here, we show a role for GBS T7SS in competition with mucosal pathobiont , both and . We further find that a GBS LXG protein contributing to this antagonism is exported by the T7SS and is intracellularly toxic to other bacteria; therefore, we have named this protein group B streptococcal L XG T oxin A (BltA). Finally, we show that BltA and its associated chaperones promote persistence within female genital tract tissues These data reveal previously unrecognized mechanisms by which GBS may compete with other mucosal opportunistic pathogens to persist within the female genital tract.
PubMed: 38915665
DOI: 10.1101/2024.06.10.598350 -
Neurosurgical Review Jun 2024The bone holes in the skull during surgical drainage were accurately located at the site of the MMA. The MMA was severed, and the hematoma was removed intraoperatively;... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The bone holes in the skull during surgical drainage were accurately located at the site of the MMA. The MMA was severed, and the hematoma was removed intraoperatively; furthermore, surgical drainage removed the pathogenic factors of CSDH. This study aimed to describe and compare the results of the new treatment with those of traditional surgical drainage, and to investigate the relevance of this approach.
METHODS
From December 2021 to June 2023, 72 patients were randomly assigned to the observation group and the control group. The control group was treated with traditional surgical drainage, while the observation group was treated with DSA imaging to accurately locate the bone holes drilled in the skull on the MMA trunk before traditional surgical drainage. The MMA trunk was severed during the surgical drainage of the hematoma. The recurrence rate, time of indwelling drainage tube, complications, mRS, and other indicators of the two groups were compared, and the changes of cytokine components and imaging characteristics of the patients were collected and analyzed.
RESULTS
Overall, 27 patients with 29-side hematoma in the observation group and 45 patients with 48-side hematoma in the control group were included in the study. The recurrence rate was 0/29 in the observation group and 4/48 in the control group, indicating that the recurrence rate in the observation group was lower than in the control group (P = .048). The mean indwelling time of the drainage tube in the observation group was 2.04 ± 0.61 days, and that in the control group was 2.48 ± 0.61 days. The indwelling time of the drainage tube in the observation group was shorter than in the control group (P = .003). No surgical complications were observed in the observation group or the control group. The differences in mRS scores before and after operation between the observation group and the control group were statistically significant (P < .001). The concentrations of cytokine IL6/IL8/IL10/VEGF in the hematoma fluid of the observation and control groups were significantly higher than those in venous blood (P < .001). After intraoperative irrigation and drainage, the concentrations of cytokines (IL6/IL8/IL10/VEGF) in the subdural hematoma fluid were significantly lower than they were preoperatively. In the observation group, the number of MMA on the hematoma side (11/29) before STA development was higher than that on the non-hematoma side (1/25), and the difference was statistically significant (P = .003).
CONCLUSION
In patients with CSDH, accurately locating the MMA during surgical trepanation and drainage, severing the MMA during drainage, and properly draining the hematoma, can reduce the recurrence rate and retention time of drainage tubes, thereby significantly improving the postoperative mRS Score without increasing surgical complications.
Topics: Humans; Hematoma, Subdural, Chronic; Male; Drainage; Female; Aged; Middle Aged; Treatment Outcome; Meningeal Arteries; Adult; Aged, 80 and over; Craniotomy
PubMed: 38914867
DOI: 10.1007/s10143-024-02501-1 -
Scientific Reports Jun 2024Variations in the biomechanical stiffness of brain tumors can not only influence the difficulty of surgical resection but also impact postoperative outcomes. In a...
Variations in the biomechanical stiffness of brain tumors can not only influence the difficulty of surgical resection but also impact postoperative outcomes. In a prospective, single-blinded study, we utilize pre-operative magnetic resonance elastography (MRE) to predict the stiffness of intracranial tumors intraoperatively and assess the impact of increased tumor stiffness on clinical outcomes following microsurgical resection of vestibular schwannomas (VS) and meningiomas. MRE measurements significantly correlated with intraoperative tumor stiffness and baseline hearing status of VS patients. Additionally, MRE stiffness was elevated in patients that underwent sub-total tumor resection compared to gross total resection and those with worse postoperative facial nerve function. Furthermore, we identify tumor microenvironment biomarkers of increased stiffness, including αSMA + myogenic fibroblasts, CD163 + macrophages, and HABP (hyaluronic acid binding protein). In a human VS cell line, a dose-dependent upregulation of HAS1-3, enzymes responsible for hyaluronan synthesis, was observed following stimulation with TNFα, a proinflammatory cytokine present in VS. Taken together, MRE is an accurate, non-invasive predictor of tumor stiffness in VS and meningiomas. VS with increased stiffness portends worse preoperative hearing and poorer postoperative outcomes. Moreover, inflammation-mediated hyaluronan deposition may lead to increased stiffness.
Topics: Humans; Meningioma; Neuroma, Acoustic; Elasticity Imaging Techniques; Female; Male; Middle Aged; Biomarkers, Tumor; Aged; Prospective Studies; Adult; Meningeal Neoplasms; Treatment Outcome; Tumor Microenvironment; Magnetic Resonance Imaging
PubMed: 38914647
DOI: 10.1038/s41598-024-64597-1 -
World Neurosurgery Jun 2024Paediatric hydrocephalus causes significant health burden globally, particularly in low and middle-income countries. There's a dearth of data from specific regions such...
The landscape of paediatric hydrocephalus in the Province of KwaZulu-Natal. A comparative analysis of the referral pattern, aetiology and management outcomes over four distinct five-year periods.
BACKGROUND
Paediatric hydrocephalus causes significant health burden globally, particularly in low and middle-income countries. There's a dearth of data from specific regions such as KwaZulu-Natal, South Africa. This study aimed to investigate the landscape of paediatric hydrocephalus, comparing four distinct five-year periods.
METHODS
Data were collected retrospectively (2003 to 2007, 2008 to 2012, and 2013 to 2017) and prospectively (2018 to 2022). Children (≤18 years) treated for hydrocephalus were included. Data on demographics, referral patterns, aetiology, treatment modalities, and outcomes were collected and analyzed.
RESULTS
A total of 3325 children were treated. The peak period was 2008 to 2012 (35.3%). Majority (51.4%) were from rural areas (p=0.013) and 47.9% were referred from regional hospitals, p=<0.001. Males (56.4%) and infants (60.2%) were predominant groups (p<0.001). Post-infectious aetiology (32.7%) was predominant (p<0.001), particularly tuberculous meningitis (54.1%). Ventriculoperitoneal shunts (VPSs) were the mainstay treatment (84.2%), with notable complication rates (20.4%), including infections (9.6%). HIV co-infection was diagnosed in 2.5% of cases. Weekend procedures were associated with VPS complications (HR1.3, CI:1.03-1.66, p=0.03). The mortality rate was 7.9%, and age ≥1 year (HR, 2.43 CI: 1.87-3.17, p<0.001), tertiary hospital referral (HR 1.48, CI: 1.06-2.04, p=0.019), VPS infection (HR, 3.63 CI: 2.66-4.95, p<0.001), acute abdomen (HR 2.17, CI: 1.11-4.25, p=0.024) and pneumonia (HR 7.32, OR 4.84 -11.06, p<0.001) were associated with mortality.
CONCLUSION
This study provides comprehensive insights into pediatric hydrocephalus in KZN. Monitoring temporal trends and predictors of outcomes will aid guide future interventions aimed at mitigating the burden of pediatric hydrocephalus in the region.
PubMed: 38914134
DOI: 10.1016/j.wneu.2024.06.103 -
PloS One 2024Tick-borne encephalitis (TBE) is usually diagnosed based on the presence of TBE virus (TBEV)-specific IgM and IgG antibodies in serum. However, antibodies induced by...
Tick-borne encephalitis (TBE) is usually diagnosed based on the presence of TBE virus (TBEV)-specific IgM and IgG antibodies in serum. However, antibodies induced by vaccination or cross-reactivity to previous flavivirus infections may result in false positive TBEV serology. Detection of TBEV RNA may be an alternative diagnostic approach to detect viral presence and circumvent the diagnostic difficulties present when using serology. Viral RNA in blood is commonly detectable only in the first viremic phase usually lasting up to two weeks, and not in the second neurologic phase, when the patients contact the health care system and undergo diagnostic work-up. TBEV RNA has previously been detected in urine in a few retrospective TBE cases in the neurologic phase, and furthermore RNA of other flaviviruses has been detected in patient saliva. In this study, blood, saliva and urine were collected from 31 hospitalised immunocompetent patients with pleocytosis and symptoms of aseptic meningitis and/or encephalitis, suspected to have TBE. We wanted to pursue if molecular testing of TBEV RNA in these patient materials may be useful in the diagnostics. Eleven of the 31 study patients were diagnosed with TBE based on ELISA detection of TBEV specific IgG and IgM antibodies. None of the study patients had TBEV RNA detectable in any of the collected patient material.
Topics: Humans; Encephalitis, Tick-Borne; Encephalitis Viruses, Tick-Borne; Saliva; RNA, Viral; Male; Female; Middle Aged; Adult; Aged; Immunoglobulin M; Immunoglobulin G; Antibodies, Viral; Aged, 80 and over; Immunocompetence; Hospitalization
PubMed: 38913668
DOI: 10.1371/journal.pone.0305603 -
JCI Insight Jun 2024
Topics: Neutrophils; Demyelinating Diseases; Humans; Meninges; Gray Matter; Male; Female; Middle Aged; Adult; Magnetic Resonance Imaging; Aged; Aging; Age Factors
PubMed: 38912582
DOI: 10.1172/jci.insight.183445 -
Journal of the Medical Library... Jan 2024In 1928, Alexander Fleming (1881-1955) identified penicillin, the world's first antibiotic. It was a chance discovery that could have easily been missed had Fleming not...
In 1928, Alexander Fleming (1881-1955) identified penicillin, the world's first antibiotic. It was a chance discovery that could have easily been missed had Fleming not taken a second look at a contaminated Petri dish. The discovery of penicillin marked a profound turning point in history as it was the first time deadly infections such as bacterial pneumonia, sepsis, diphtheria, meningitis, and puerperal fever after childbirth could be cured, and it paved the way for the development of additional antibiotics. The Alexander Fleming Laboratory Museum, one of several London Museums of Health and Medicine, is a reconstruction of Fleming's laboratory in its original location at St. Mary's Hospital. As if stepping back in time, visitors gain a glimpse into the man, his bacteriology work, and the events surrounding this important finding. For those unable to travel to London, this article provides a brief narrative of the fascinating story.
Topics: History, 20th Century; Humans; Penicillins; History, 19th Century; Anti-Bacterial Agents; London
PubMed: 38911526
DOI: 10.5195/jmla.2024.1780 -
Journal of Neuroendovascular Therapy 2024To report the rare case of a patient with a perianeurysmal cyst following stent-assisted coil embolization of an unruptured vertebral artery aneurysm.
OBJECTIVE
To report the rare case of a patient with a perianeurysmal cyst following stent-assisted coil embolization of an unruptured vertebral artery aneurysm.
CASE PRESENTATION
A 63-year-old woman underwent stent-assisted coil embolization for an unruptured vertebral artery aneurysm embedded in the brainstem (pons). Complete occlusion of the aneurysm was successfully achieved. However, subsequent magnetic resonance imaging (MRI) conducted 8 months after the procedure showed perilesional edematous changes surrounding the aneurysm, and at 20 months, cyst formation was observed in the vicinity of the aneurysm. Progressive enlargement of the cyst eventually led to the development of paralysis and dysphagia, necessitating cyst fenestration surgery. Although postoperative reduction in the cyst size was achieved, the patient experienced complications in the form of aspiration pneumonia and bacterial meningitis, which resulted in a life-threatening condition.
CONCLUSION
Aneurysms embedded in the brain parenchyma should be carefully followed up, recognizing the risk of perianeurysmal cyst formation after coil embolization.
PubMed: 38911484
DOI: 10.5797/jnet.cr.2023-0088 -
Open Medicine (Warsaw, Poland) 2024To investigate the clinical efficacy of dexamethasone (Dex) combined with isoniazid in tuberculous meningitis (TBM) and its effect on peripheral blood T cell subsets.
OBJECTIVE
To investigate the clinical efficacy of dexamethasone (Dex) combined with isoniazid in tuberculous meningitis (TBM) and its effect on peripheral blood T cell subsets.
METHODS
A total of 235 patients with TBM were divided into the control group (117 cases) and the observation group (118 cases). Both groups were given conventional treatment, the control group was further given isoniazid, and the observation group was further given Dex combined with isoniazid. The therapeutic effect and improvement of clinical symptoms were evaluated, peripheral blood T lymphocyte subsets and neurological function were observed, and patients' prognosis was evaluated.
RESULTS
The total effective rate of the observation group was higher. The recovery time of cerebrospinal fluid (CSF) pressure, CSF protein content, CSF cell count, and hospital stays in the observation group were shorter. The duration of cervicogenic headache, fever, vomiting, and coma in the observation group was shorter. CD3 and CD4/CD8 proportions in the observation group were higher, and CD8 proportion was lower. The NIHSS score and MRS score of the observation group were lower, as well as the incidence of adverse reactions.
CONCLUSION
Dex combined with isoniazid alleviates clinical symptoms and neurological abnormalities and regulates peripheral blood T cell subsets in TBM.
PubMed: 38911253
DOI: 10.1515/med-2024-0948 -
Cureus May 2024Immune effector cell-associated neurotoxicity syndrome (ICANS) is a well-known side effect of chimeric antigen receptor (CAR) T-cell therapy but has occasionally been...
Glofitamab-Associated Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) Presenting as Serial Seizures and Responding Positively to Antiseizure Drugs and Anakinra: A Case Report.
Immune effector cell-associated neurotoxicity syndrome (ICANS) is a well-known side effect of chimeric antigen receptor (CAR) T-cell therapy but has occasionally been described with immune checkpoint inhibitors as well. Glofitamab-associated ICANS with a bispecific monoclonal antibody has rarely been reported. The patient is a 63-year-old male with a history of mantle cell lymphoma, diagnosed at age 37, and aggressive large-cell B-cell lymphoma, diagnosed at age 50. Despite adequate chemotherapy, immunotherapy, autologous stem cell transplantation, and CAR T-cell therapy, there were several relapses, including meningeal carcinomatosis at age 61 and intracerebral lymphoma at age 62. For this reason, glofitamab was started. One week after the ninth cycle, the patient developed drowsiness, behavioral changes, word-finding difficulties, aphasia, focal to bilateral tonic-clonic seizures, and focal onset seizures, which resolved after 16 days with levetiracetam, valproic acid, lorazepam, and midazolam. Since there was no infectious disease, electrolyte disturbance, metabolic disorder, cardiovascular disease, or relapse of lymphoma, glofitamab-associated ICANS was suspected, and anakinra was administered. The case shows that ICANS with drowsiness, behavioral changes, aphasia, and seizures can develop with glofitamab and that patients with structural brain abnormalities may be prone to this.
PubMed: 38910651
DOI: 10.7759/cureus.60833