Dorzolamide intermediates with potential anti-inflammatory activity.

Dorzolamide (DZD), a Carbonic anhydrase (CA) inhibitor clinically used to lower intraocular pressure, exhibits anti-inflammatory effects owing to the drug's ability to inhibit the TIR domain-containing adaptor protein (TIRAP)-mediated signalling in macrophages. Here, we investigated whether DZD intermediates also demonstrate any anti-inflammatory property like DZD but with a reduced inhibition of CA. We found that several intermediates of DZD show increased binding to TIRAP at the common interface of kinases, such as Protein kinase C-delta (PKCδ) and Bruton's tyrosine kinase (BTK).

The self-organized structure of glioma oncostreams and the disruptive role of passive cells.

Oncostreams are self-organized structures formed by spindle-like, elongated, self-propelled cells recently described in glioblastomas and especially in gliosarcomas. Cells within these structures either move as large clusters in one main direction, flocks, or as linear, intermingling collections of cells advancing in opposite directions, streams. Round, passive cells are also observed, either inside or segregated from the oncostreams.

Cell and gene therapy in neuro-oncology.

The majority of primary brain tumors are gliomas, among which glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. GBM has a median survival of 18-24 months, and despite extensive research it remains incurable, thus novel therapies are urgently needed. The current standard of care is a combination of surgery, radiation, and chemotherapy, but still remains ineffective due to the invasive nature and high recurrence of gliomas.

Colo-colonic intussusception secondary to Burkitt lymphoma with concurrent malignant small bowel mesh adhesion.

Intussusception is a rare presentation in adult population and usually occurs secondary to an underlying pathology. We report an unusual case of a 28-year-old female who developed a colo-colonic intussusception secondary to Burkitt lymphoma which was managed with an extended right hemicolectomy. The case was further complicated by a segment of small bowel with malignant adhesion to a prosthetic mesh requiring resection of the involved segment of small bowel.

Advancing Cardiovascular Risk Assessment with Artificial Intelligence: Opportunities and Implications in North Carolina.

Cardiovascular disease mortality is increasing in North Carolina with persistent inequality by race, income, and location. Artificial intelligence (AI) can repurpose the widely available electrocardiogram (ECG) for enhanced assessment of cardiac dysfunction. By identifying accelerated cardiac aging from the ECG, AI offers novel insights into risk assessment and prevention.

Assessment of Knowledge and Attitudes Related to HIV/AIDS Among the Population With Increasing Incidence Rate.

Introduction Lack of awareness and negative attitudes toward people living with HIV/AIDS (PLWHA) are key barriers to minimizing the transmission of HIV. Therefore, the present survey-based study aimed to assess the knowledge regarding HIV/AIDS and attitudes toward PLWHA. Methods In the present study, we collected data from 612 Kyrgyz national participants using a self-administered questionnaire.

Spatiotemporal Insights into Glioma Oncostream Dynamics: Unraveling Formation, Stability, and Disassembly Pathways.

Glioblastoma (GBM) remains a challenge in Neuro-oncology, with a poor prognosis showing only a 5% survival rate beyond two years. This is primarily due to its aggressiveness and intra-tumoral heterogeneity, which limits complete surgical resection and reduces the efficacy of existing treatments. The existence of oncostreams-neuropathological structures comprising aligned spindle-like cells from both tumor and non-tumor origins- is discovered earlier.

Hemodynamics of Saline Flushing in Endoscopic Imaging of Partially Occluded Coronary Arteries.

Purpose: Intravascular endoscopy can aid in the diagnosis of coronary atherosclerosis by providing direct color images of coronary plaques. The procedure requires a blood-free optical path between the catheter and plaque, and achieving clearance safely remains an engineering challenge. In this study, we investigate the hemodynamics of saline flushing in partially occluded coronary arteries to advance the development of intravascular forward-imaging catheters that do not require balloon occlusion.

Lipid A Is a Potent Adjuvant That Induces Sterilizing Immunity against Leptospirosis.

Leptospirosis is a globally significant zoonotic disease. The current inactivated vaccine offers protection against specific serovars but does not provide complete immunity. Various surface antigens, such as immunoglobulin-like proteins (LigA and LigB), have been identified as potential subunit vaccine candidates.

Differential modulation of innate immune response by lipopolysaccharide of .

Leptospirosis is a worldwide zoonosis caused by pathogenic spp. having more than 300 serovars. These serovars can infect a variety of hosts, some being asymptomatic carriers and others showing varied symptoms of mild to severe infection.

A Complex Case of Extensive Systemic Amyloidosis With Underlying Monoclonal Gammopathy.

Systemic amyloid light chain, or primary amyloidosis (AL amyloidosis), is a serious medical condition that leads to the deposition of abnormal proteins called amyloid fibrils in various organs of the body. AL amyloidosis can present with different symptoms, which can make diagnosis challenging. This case report presents a clinical scenario of a 53-year-old female patient who had come in for shortness of breath and lower extremity swelling and was found to have acute on chronic pulmonary embolism.

Brevundimonas diminuta-Induced Lung Abscess in an Immunocompetent Adult: A Rare Case Report.

Lung abscesses caused by () are a rare occurrence, particularly in immunocompetent adults. We present the case of a 47-year-old male with a history of COPD, bipolar disorder, and seizure disorder, who presented with a productive cough, worsening shortness of breath, yellow sputum, weight loss, and fatigue over a period of three weeks. Clinical examination revealed decreased breath sounds in the left upper lung zones.

A Unique Case of Chylothorax Occurring Post-Chest Tube Insertion.

Chylothorax is a relatively rare condition characterized by the accumulation of chyle, a milky lymphatic fluid, within the pleural space. It occurs because of disruption or obstruction of the thoracic duct or its tributaries, leading to chyle leakage into the pleural cavity. We present an interesting case of chylothorax that occurred as a complication post-chest tube insertion.

Pneumothorax Ex Vacuo: A Rare Complication of PleurX Catheter Insertion.

Pneumothorax ex vacuo (PEV) is a rare type of pneumothorax that occurs when air enters the pleural space in the chest cavity due to an increase in the volume of the lungs or a reduction in the volume of the surrounding lung tissue. Unlike a typical pneumothorax, which involves the collapse of the lung due to air accumulation, pneumothorax ex vacuo occurs when the lung itself cannot expand properly, often due to underlying lung disease or conditions such as pulmonary fibrosis or atelectasis. The mechanism is compensatory to the lung entrapment.

A Case of Concurrent Infection With Syphilis and Monkeypox in an Immunosuppressed Individual.

Monkeypox and syphilis are two distinct infectious diseases that can cause severe health complications in infected patients and can share clinical manifestations, making their simultaneous occurrence challenging to diagnose and manage. Here, we present a case report of a patient with the coinfection of monkeypox and syphilis, highlighting the clinical presentation and treatment considerations. This case underlines the importance of considering coinfections in patients presenting with atypical clinical manifestations and risk factors.

Combined cytotoxic and immune-stimulatory gene therapy using Ad-TK and Ad-Flt3L: Translational developments from rodents to glioma patients.

Gliomas are the most prevalent and devastating primary malignant brain tumors in adults. Despite substantial advances in understanding glioma biology, there have been no regulatory drug approvals in the US since bevacizumab in 2009 and tumor treating fields in 2011. Recent phase III clinical trials have failed to meet their prespecified therapeutic primary endpoints, highlighting the need for novel therapies.

Crystal structure of a variable region segment of Leptospira host-interacting outer surface protein, LigA, reveals the orientation of Ig-like domains.

Leptospiral immunoglobulin-like (Lig) protein family is a surface-exposed protein from the pathogenic Leptospira. The Lig protein family has been identified as an essential virulence factor of L. interrogan.

Dorzolamide suppresses PKCδ -TIRAP-p38 MAPK signaling axis to dampen the inflammatory response.

Sepsis is a syndrome due to microbial infection causing impaired multiorgan function. Its underlying cause is immune dysfunction and macrophages play an essential role. TIRAP interaction with PKCδ in macrophage was studied, revealing downstream signaling by Western blot and quantitative reverse transcriptase PCR.

Generation of 3D ex vivo mouse- and patient-derived glioma explant slice model for integration of confocal time-lapse imaging and spatial analysis.

Development of spatial-integrative pre-clinical models is needed for glioblastoma, which are heterogenous tumors with poor prognosis. Here, we present an optimized protocol to generate three-dimensional ex vivo explant slice glioma model from orthotopic tumors, genetically engineered mouse models, and fresh patient-derived specimens. We describe a step-by-step workflow for tissue acquisition, dissection, and sectioning of 300-μm tumor slices maintaining cell viability.