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MBio Jun 2024causes cryptococcosis, one of the most prevalent fungal diseases, generally characterized by meningitis. There is a limited and not very effective number of drugs...
UNLABELLED
causes cryptococcosis, one of the most prevalent fungal diseases, generally characterized by meningitis. There is a limited and not very effective number of drugs available to combat this disease. In this manuscript, we show the host defense peptide mimetic brilacidin (BRI) as a promising antifungal drug against . BRI can affect the organization of the cell membrane, increasing the fungal cell permeability. We also investigated the effects of BRI against the model system by analyzing libraries of mutants grown in the presence of BRI. In , BRI also affects the cell membrane organization, but in addition the cell wall integrity pathway and calcium metabolism. experiments show BRI significantly reduces survival inside macrophages and partially clears lung infection in an immunocompetent murine model of invasive pulmonary cryptococcosis. We also observed that BRI interacts with caspofungin (CAS) and amphotericin (AmB), potentiating their mechanism of action against . BRI + CAS affects endocytic movement, calcineurin, and mitogen-activated protein kinases. Our results indicate that BRI is a novel antifungal drug against cryptococcosis.
IMPORTANCE
Invasive fungal infections have a high mortality rate causing more deaths annually than tuberculosis or malaria. Cryptococcosis, one of the most prevalent fungal diseases, is generally characterized by meningitis and is mainly caused by two closely related species of basidiomycetous yeasts, and . There are few therapeutic options for treating cryptococcosis, and searching for new antifungal agents against this disease is very important. Here, we present brilacidin (BRI) as a potential antifungal agent against . BRI is a small molecule host defense peptide mimetic that has previously exhibited broad-spectrum immunomodulatory/anti-inflammatory activity against bacteria and viruses. BRI alone was shown to inhibit the growth of , acting as a fungicidal drug, but surprisingly also potentiated the activity of caspofungin (CAS) against this species. We investigated the mechanism of action of BRI and BRI + CAS against . We propose BRI as a new antifungal agent against cryptococcosis.
PubMed: 38916308
DOI: 10.1128/mbio.01031-24 -
Cureus May 2024Background Spinal dysraphism, characterized by incomplete closure of neural and bone spinal structures, manifests as congenital fusion abnormalities along the dorsal...
Background Spinal dysraphism, characterized by incomplete closure of neural and bone spinal structures, manifests as congenital fusion abnormalities along the dorsal midline, involving the skin, subcutaneous tissue, meninges, vertebrae, and neural tissue. Magnetic resonance imaging (MRI), the preferred imaging modality for assessing spinal dysraphism across all age groups, provides direct visualization of the spinal cord without the need for contrast or ionizing radiation while also eliminating bone artifacts and allowing multiplanar imaging. The objective of this study was to evaluate the range of spinal dysraphism lesions and assess the significance of MRI in their evaluation. Methodology Thirty patients with suspected spinal dysraphism underwent evaluation at the Medical College Hospital and Study Centre in Vijayapur, India. This cross-sectional observational study included patients diagnosed or provisionally diagnosed with spinal dysraphism based on clinical and imaging profiles. Cases were identified through preliminary findings on radiographs. Results The study encompassed individuals aged one month to 20 years, with the largest proportion of patients (36.67%) falling within the 1-5-year age group. Spina bifida was the most prevalent spinal abnormality, accounting for 70% of cases. In 12 patients (40%), the most prevalent location of involvement was the lumbosacral spine. Conclusion MRI provides excellent tissue differentiation, particularly of lipomatous tissue, with reproducible and comprehensive section planes and relative operator independence. Moreover, MRI is beneficial for children with suspected spinal dysraphism as it can be performed without ionizing radiation, biological risks, or the need for intrathecal contrast media.
PubMed: 38916024
DOI: 10.7759/cureus.60972 -
Cureus May 2024This case emphasizes the significance of recognizing and managing species. Here, we present a unique case of species isolated from the cerebrospinal fluid of a...
This case emphasizes the significance of recognizing and managing species. Here, we present a unique case of species isolated from the cerebrospinal fluid of a 60-year-old female with recently diagnosed human immunodeficiency virus (HIV) and small cell carcinoma of the lung. Management involved a two-week course of intravenous vancomycin. species are infrequently encountered in clinical practice. Sharing this case report aims to enhance the limited understanding of species infections and encourages discussion among healthcare professionals regarding its diagnosis and management.
PubMed: 38915964
DOI: 10.7759/cureus.61072 -
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...
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 LXG Toxin 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.
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