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MBio Jun 2024Mitogen-activated protein kinase (MAPK) pathways are fundamental to the regulation of biological processes in eukaryotic organisms. The basidiomycete , known for causing...
Mitogen-activated protein kinase (MAPK) pathways are fundamental to the regulation of biological processes in eukaryotic organisms. The basidiomycete , known for causing fungal meningitis worldwide, possesses five MAPKs. Among these, Cpk1, Hog1, and Mpk1 have established roles in sexual reproduction, stress responses, and cell wall integrity. However, the roles of Cpk2 and Mpk2 are less understood. Our study elucidates the functional interplay between the Cpk1/Cpk2 and Mpk1/Mpk2 MAPK pathways in . We discovered that overexpression compensates for Δ mating deficiencies via the Mat2 transcription factor, revealing functional redundancy between Cpk1 and Cpk2. We also found that Mpk2 is phosphorylated in response to cell wall stress, a process regulated by the MAPK kinase (MAP2K) Mkk2 and MAP2K kinases (MAP3Ks) Ssk2 and Ste11. Overexpression of partially restores cell wall integrity in Δ by influencing key cell wall components, such as chitin and the polysaccharide capsule. Contrarily, overexpression cannot restore thermotolerance and cell membrane integrity in Δ. These results suggest that Mpk1 and Mpk2 have redundant and opposing roles in the cellular response to cell wall and membrane stresses. Most notably, the dual deletion of and restores wild-type mating efficiency in Δ mutants via upregulation of the mating-regulating transcription factors and , suggesting that the Mpk1 and Mpk2 cooperate to negatively regulate the pheromone-responsive Cpk1 MAPK pathway. Our research collectively underscores a sophisticated regulatory network of cryptococcal MAPK signaling pathways that intricately govern sexual reproduction and cell wall integrity, thereby controlling fungal development and pathogenicity.IMPORTANCEIn the realm of fungal biology, our study on offers pivotal insights into the roles of specific proteins called mitogen-activated protein kinases (MAPKs). Here, we discovered the cryptic functions of Cpk2 and Mpk2, two MAPKs previously overshadowed by their dominant counterparts Cpk1 and Mpk1, respectively. Our findings reveal that these "underdog" proteins are not just backup players; they play crucial roles in vital processes like mating and cell wall maintenance in . Their ability to step in and compensate when their dominant counterparts are absent showcases the adaptability of . This newfound understanding not only enriches our knowledge of fungal MAPK mechanisms but also underscores the intricate balance and interplay of proteins in ensuring the organism's survival and adaptability.
PubMed: 38874410
DOI: 10.1128/mbio.01156-24 -
Eastern Mediterranean Health Journal =... May 2024Meningitis is still a major public health challenge globally. Both the viral and bacterial forms of the disease have been reported worldwide. In 2023, around 200...
BACKGROUND
Meningitis is still a major public health challenge globally. Both the viral and bacterial forms of the disease have been reported worldwide. In 2023, around 200 children with suspected meningitis were admitted to hospital in Halabja Governorate, Iraq. No outbreak of meningitis had been reported previously in that region.
AIMS
To investigate the aetiology and epidemiology of meningitis among children in Halabja Governorate, Iraq, and expedite clinical management and prevention.
METHODOLOGY
Blood and cerebrospinal fluid specimens were collected from 197 children admitted to Halabja Paediatric and Maternity Teaching Hospital from 1 March to 1 July 2023 and analysed. The sample t-test was used to compare the haematological, serological and biochemical characteristics of the samples.
RESULTS
The majority (76.6%) of the children were aged 2-9 years and 54% were males. The clinical manifestations of the disease were fever (100.0%), headache (89.0%), vomiting (85.7%), and photophobia (72.4%); none of the children had convulsions. The mean values for both neutrophil count and C-reactive protein were statistically significantly raised (P < 0.05) and the red blood cells, white blood cells and neutrophil counts, and lactate dehydrogenase values were statistically significantly raised (P < 0.05). The causative organism was enterovirus (98.5%), with sporadic cases of streptococcal meningitis (1.5%). All the patients recovered fully.
CONCLUSION
The rapid diagnosis of the disease was crucial to the therapeutic and prevention control measures for the outbreak. Although it is still unclear how and where this outbreak started, contaminated drinking water and transmission among children in nurseries and schools are suspected. Further investigations are recommended to determine the source of the enterovirus and identify the virus species and serotypes.
Topics: Humans; Iraq; Child; Child, Preschool; Male; Disease Outbreaks; Female; Meningitis, Viral; Adolescent; Infant; Meningitis, Bacterial
PubMed: 38874294
DOI: 10.26719/2024.30.5.350 -
Turkish Neurosurgery Jan 2024Subarachnoid haemorrhage (SAH) often leads to shunt-dependent hydrocephalus (SDH). This study compares microsurgical clipping and endovascular therapy (EVT) for managing...
AIM
Subarachnoid haemorrhage (SAH) often leads to shunt-dependent hydrocephalus (SDH). This study compares microsurgical clipping and endovascular therapy (EVT) for managing SDH in SAH patients with hydrocephalus.
MATERIAL AND METHODS
A retrospective study conducted from July 2018 to December 2022 included 67 SAH patients with acute hydrocephalus. Data on demographic, clinical, and radiological parameters, such as age, gender, GCS scores, Hunt and Hess grade, Fischer score, EVD duration, complications, Omaya reservoir placement, CSF drainage, and outcomes, were collected. Statistical analyses, including univariate analysis and stepwise logistic regression, identified significant risk factors for shunt dependence.
RESULTS
Among the 67 patients, 33 underwent microsurgical clipping, and 34 received EVT. Spasmolysis reduced shunt dependency, while early EVD placement correlated with reduced shunt dependence (p = 0.002). The Omaya reservoir helped manage meningitis but was associated with shunt dependency (p = 0.04). Perioperative infarct was a significant risk factor for shunt dependence on multiple logistic regression analysis (p = 0.05). No significant difference was observed in patient outcomes between the two treatment groups. However, EVT patients had shorter ICU and hospital stays.
CONCLUSION
This study underscores that clinical vasospasm management through spasmolysis may reduce shunt dependency. Overall, both microsurgical clipping and EVT offer similar long-term outcomes and efficacy to prevent shunt dependence, but EVT has the advantage of shorter hospital stays. These findings provide crucial insights for clinical decision-making and patient care in SDH following SAH.
PubMed: 38874254
DOI: 10.5137/1019-5149.JTN.45739-23.1 -
Turkish Neurosurgery Aug 2023Intradiploic meningiomas are rare neoplasms, often mistaken for metastases or malignant bone tumors. Surgical management can be challenging, considering their diffusive...
AIM
Intradiploic meningiomas are rare neoplasms, often mistaken for metastases or malignant bone tumors. Surgical management can be challenging, considering their diffusive bony invasion. Two main critical decisions need to be taken: the timing for cranial vault reconstruction and the choice of the adequate material for cranioplasty. We believe that this case underscores the complexity of such lesions, the importance of a prompt devascularization, and the pivotal role of an immediate reconstruction to avoid the additional morbidity of a re-do surgery.
MATERIAL AND METHODS
We report a case of 68-year-old men who presented with slow growing right parietal bone swelling he noted many years before, but for which he didn't seek medical attentions, associated with mild contralateral hemiparesis. Neuroradiological examinations revealed a giant extradural intradiploic tumor affecting the right temporo-parietal bone and conditioning significant compression of the underlying brain. We planned a surgical strategy to deafferent the tumor and to reduce the intraoperative bleeding. At first, a circumferential craniectomy centered upon the lesion was performed, then it was devascularized by means of surgical ligation of the ipsilateral superficial temporal artery (STA) and middle meningeal artery (MMA); these steps allowed a subsequent en block tumor excision, despite its large size, without significant blood loss and respecting the oncological principles. At the end, a contextual calvarial reconstruction was performed using a precurved titanium mesh.
RESULTS
Was discharged seven days after surgery with complete recovery of the left-sided motor deficit. Thereafter, he underwent scheduled outpatient evaluations and radiological exams. After 1 year, the Modified Rankin Scale (MRS) was 1, with no evidence of recurrent disease.
CONCLUSION
Surgical complications can be reduced adopting an optimal preoperative work-up and a tailored surgical strategy focused on early tumor deafferentation. Moreover, an immediate cranial vault reconstruction avoids the risks related to a second procedure.
PubMed: 38874243
DOI: 10.5137/1019-5149.JTN.43641-23.2 -
PLoS Neglected Tropical Diseases Jun 2024Tacheng tick virus 2 (TcTV-2) is an emerging tick-borne virus belonging to the genus Uukuvirus in the family Phenuiviridae. Initially isolated in 2019 from a patient in...
BACKGROUND
Tacheng tick virus 2 (TcTV-2) is an emerging tick-borne virus belonging to the genus Uukuvirus in the family Phenuiviridae. Initially isolated in 2019 from a patient in Xinjiang Uygur Autonomous Region (XUAR), northwestern China, who developed fever and headache after a tick bite, TcTV-2 was concurrently molecularly detected in hard ticks across various countries, including China, Kazakhstan, Romania, and Turkey. This study conducted a retrospective epidemiological investigation of TcTV-2 infection.
METHODOLOGY
In this retrospective cohort study, we collected samples from 47 tick-bitten patients, 984 herdsmen, 7 Asian badgers, 13 red foxes, and 168 Hyalomma asiaticum tick egg batches. Patients' samples were primarily analyzed by using high-throughput sequencing, targeting the V3-V4 region of the bacterial 16S rRNA gene and viral cDNA libraries. Typical tick-borne pathogens were further confirmed using RT-PCR and detected in Asian badgers, red foxes and Hy. asiaticum tick egg batches. We also conducted enzyme-linked immunosorbent assay (ELISA) to detected specific IgM and IgG antibodies against TcTV-2 in herdsmen. Phylogenetic analysis was performed to genetically characterize TcTV-2 detected in this study.
PRINCIPAL FINDINGS
TcTV-2 was detected in various samples, including blood, urine, and throat swabs from 12.77% (6/47) tick-bitten patients. It was found in blood samples of 14.29% (1/7) of wild badgers, 7.69% (1/13) of red foxes, and 13.69% (23/168) of Hy. asiaticum egg batches. Furthermore, ELISA results revealed that 9.55% (94/984) of the serum samples (34 from males and 60 from females) were tested positive for TcTV-2-specific IgG, while 2.95% (29/984, 7 males and 22 females) showed positivity for TcTV-2-specific IgM. Additionally, 1.02% (10/984, 4 males and 6 females) of the sera tested positive for both TcTV-2-specific IgM and IgG. Phylogenetic analysis indicated that the TcTV-2 strains detected in this study were genetically similar, regardless of their origin and host species.
CONCLUSIONS
Clinical symptoms of TcTV-2 infection in patients are nonspecific, with common symptoms including headache, fever, asthenia, vomiting, myalgia, rash, and meningitis-like signs. TcTV-2 can be detected in blood, urine, and throat swab samples of infected patients. Among local herdsmen, 9.55% tested positive for TcTV-2-specific IgG and 2.95% for TcTV-2-specific IgM. Importantly, TcTV-2 can be transovarially transmitted in Hy. asiaticum ticks, and the Asian badgers and red foxes are potential reservoirs of TcTV-2.
Topics: Retrospective Studies; Animals; Male; Humans; Female; Phylogeny; Middle Aged; Adult; China; Antibodies, Viral; Young Adult; Immunoglobulin G; Adolescent; Immunoglobulin M; Tick-Borne Diseases; Aged; Child; Tick Bites; Foxes
PubMed: 38870100
DOI: 10.1371/journal.pntd.0012168 -
Microbiology Spectrum Jun 2024is a fungal pathogen that causes cryptococcosis primarily in immunocompromised patients, such as those with HIV/AIDS. One survival mechanism of during infection is...
is a fungal pathogen that causes cryptococcosis primarily in immunocompromised patients, such as those with HIV/AIDS. One survival mechanism of during infection is melanin production, which catalyzed by laccase and protects fungal cells against immune attack. Hence, the comparative assessment of laccase activity is useful for characterizing cryptococcal strains. We serendipitously observed that culturing with food coloring resulted in degradation of some dyes with phenolic structures. Consequently, we investigated the color changes for the food dyes metabolized by laccase and by using this effect explored the development of a colorimetric assay to measure laccase activity. We developed several versions of a food dye-based colorimetric laccase assay that can be used to compare the relative laccase activities between different strains. We found that phenolic color degradation was glucose-dependent, which may reflect changes in the reduction properties of the media. Our food color-based colorimetric assay has several advantages, including lower cost, irreversibility, and not requiring constant monitoring , over the commonly used 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay for determining laccase activity. This method has potential applications to bioremediation of water pollutants in addition to its use in determining laccase virulence factor expression.IMPORTANCE is present in the environment, and while infection is common, disease occurs mostly in immunocompromised individuals. infection in the lungs results in symptoms like pneumonia, and consequently, cryptococcal meningitis occurs if the fungal infection spreads to the brain. The laccase enzyme catalyzes the melanization reaction that serves as a virulence factor for . Developing a simple and less costly assay to determine the laccase activity in strains can be useful for a variety of procedures ranging from studying the relative virulence of cryptococci to environmental pollution studies.
PubMed: 38869282
DOI: 10.1128/spectrum.00442-24 -
Cureus May 2024Lyme borreliosis (LB) is a complex tick-borne illness with diverse presentations. We report a case of LB meningitis with herpes simplex virus-1 (HSV-1) co-infection in a...
Lyme borreliosis (LB) is a complex tick-borne illness with diverse presentations. We report a case of LB meningitis with herpes simplex virus-1 (HSV-1) co-infection in a 55-year-old woman initially presenting with isolated facial nerve palsy. This case illustrates the multifaceted diagnostic challenges associated with Lyme co-infections. It emphasizes the need for thorough testing to identify all potential pathogens and the importance of differentiating between true co-infection and incidental HSV-1 reactivation. Understanding these complexities is crucial for guiding appropriate treatment decisions.
PubMed: 38868243
DOI: 10.7759/cureus.60213 -
Heliyon Jun 2024Chronic inflammatory diseases are caused due to prolonged inflammation at a specific site of the body. Among other inflammatory diseases, bacterial meningitis, chronic... (Review)
Review
Chronic inflammatory diseases are caused due to prolonged inflammation at a specific site of the body. Among other inflammatory diseases, bacterial meningitis, chronic obstructive pulmonary disease (COPD), atherosclerosis and inflammatory bowel diseases (IBD) are primarily focused on because of their adverse effects and fatality rates around the globe in recent times. In order to come up with novel strategies to eradicate these diseases, a clear understanding of the mechanisms of the diseases is needed. Similarly, detailed insight into the mechanisms of commercially available drugs and potent lead compounds from natural sources are also important to establish efficient therapeutic effects. Zebrafish is widely accepted as a model to study drug toxicity and the pharmacokinetic effects of the drug. Moreover, researchers use various inducers to trigger inflammatory cascades and stimulate physiological changes in zebrafish. The effect of these inducers contrasts with the type of zebrafish used in the investigation. Hence, a thorough analysis is required to study the current advancements in the zebrafish model for chronic inflammatory disease suppression. This review presents the most common inflammatory diseases, commercially available drugs, novel therapeutics, and their mechanisms of action for disease suppression. The review also provides a detailed description of various zebrafish models for these diseases. Finally, the future prospects and challenges for the same are described, which can help the researchers understand the potency of the zebrafish model and its further exploration for disease attenuation.
PubMed: 38867970
DOI: 10.1016/j.heliyon.2024.e31862 -
The American Journal of Emergency... Jun 2024We present a three patient case series of infants who presented to the pediatric emergency department with fever, bulging anterior fontanelle (BAF), and an omicron...
We present a three patient case series of infants who presented to the pediatric emergency department with fever, bulging anterior fontanelle (BAF), and an omicron variant COVID-19 infection. All patients had a benign course, none developed meningitis, and all had symptom resolution after two days. Considerations for neuroimaging and lumbar puncture are discussed. This case series adds to the previously published case reports of infants with COVID-19, fever and BAF and further describes a variant in the presenting symptomology of COVID-19 infection in infants under 12 months. Acute and primary care providers who treat infants should consider COVID-19 testing in patients who are well appearing, with fever and BAF.
PubMed: 38866626
DOI: 10.1016/j.ajem.2024.06.003 -
Cell Reports. Medicine Jun 2024Leptomeningeal disease (LMD) remains a rapidly lethal complication for late-stage melanoma patients. Here, we characterize the tumor microenvironment of LMD and...
Leptomeningeal disease (LMD) remains a rapidly lethal complication for late-stage melanoma patients. Here, we characterize the tumor microenvironment of LMD and patient-matched extra-cranial metastases using spatial transcriptomics in a small number of clinical specimens (nine tissues from two patients) with extensive in vitro and in vivo validation. The spatial landscape of melanoma LMD is characterized by a lack of immune infiltration and instead exhibits a higher level of stromal involvement. The tumor-stroma interactions at the leptomeninges activate tumor-promoting signaling, mediated through upregulation of SERPINA3. The meningeal stroma is required for melanoma cells to survive in the cerebrospinal fluid (CSF) and promotes MAPK inhibitor resistance. Knocking down SERPINA3 or inhibiting the downstream IGR1R/PI3K/AKT axis results in tumor cell death and re-sensitization to MAPK-targeting therapy. Our data provide a spatial atlas of melanoma LMD, identify the tumor-promoting role of meningeal stroma, and demonstrate a mechanism for overcoming microenvironment-mediated drug resistance in LMD.
PubMed: 38866016
DOI: 10.1016/j.xcrm.2024.101606