Clinical Applications of PET Imaging in Alzheimer's Disease.

Alzheimer's disease (AD) involves a complex pathophysiology of neurodegeneration that leads to severe cognitive deficiencies. Understanding the molecular alterations that underlie this disease is fundamental to clinical management and therapeutic innovation. Functional imaging with positron emission tomography (PET) enables a visualization of these impaired pathways, such as cerebral hypometabolism, amyloid and tau accumulation, and neurotransmitter dysfunction.

Structural and Molecular Imaging of Aging Brain: A Focus on MR Imaging and PET Modalities.

The process of aging in the brain is reflective of various factors including the environment, lifestyle, genetics, and management of concurrent chronic conditions. Aging in the brain leads to observable structural changes on neuroimaging, such as brain volume reduction, neuronal atrophy, and synaptic loss, which affect higher cognitive functions. Positron emission tomography imaging can help visualize these changes earlier before structural changes even take place and the associated decline in brain function, revealing important insights into how the brain ages and the impact on neural connectivity and cognitive abilities.

Influenza vaccination stimulates maturation of the human T follicular helper cell response.

The differentiation and specificity of human CD4 T follicular helper cells (T cells) after influenza vaccination have been poorly defined. Here we profiled blood and draining lymph node (LN) samples from human volunteers for over 2 years after two influenza vaccines were administered 1 year apart to define the evolution of the CD4 T cell response. The first vaccination induced an increase in the frequency of circulating T (cT) and LN T cells at week 1 postvaccination.

Endoscopic-Assisted Cochlear Implantation in Far Advanced Otosclerosis.

Objectives: To evaluate the effectiveness of cochlear implantation (CI) in case of far advanced otosclerosis and to evaluate the value of using intraoperative otoendoscopy to facilitate the identification of the round window membrane and the scala tympani without the need to remove the posterior canal wall or to perform a subtotal petrosectomy.

Study Design: Retrospective case-series study.

Setting: Tertiary academic CI center.

Unconventional activation of PRKDC by TNF-α: deciphering its crucial role in Th1-mediated inflammation beyond DNA repair as part of the DNA-PK complex.

Background: The DNA-dependent protein kinase (DNA-PK) complex comprises a catalytic (PRKDC) and two requisite DNA-binding (Ku70/Ku80) subunits. The role of the complex in repairing double-stranded DNA breaks (DSBs) is established, but its role in inflammation, as a complex or individual subunits, remains elusive. While only ~ 1% of PRKDC is necessary for DNA repair, we reported that partial inhibition blocks asthma in mice without causing SCID.

Spatiotemporal development of the human T follicular helper cell response to Influenza vaccination.

We profiled blood and draining lymph node (LN) samples from human volunteers after influenza vaccination over two years to define evolution in the T follicular helper cell (TFH) response. We show LN TFH cells expanded in a clonal-manner during the first two weeks after vaccination and persisted within the LN for up to six months. LN and circulating TFH (cTFH) clonotypes overlapped but had distinct kinetics.

Pulmonary inflammation and fibroblast immunoregulation: from bench to bedside.

In recent years, there has been an explosion of interest in how fibroblasts initiate, sustain, and resolve inflammation across disease states. Fibroblasts contain heterogeneous subsets with diverse functionality. The phenotypes of these populations vary depending on their spatial distribution within the tissue and the immunopathologic cues contributing to disease progression.

The Brain Tumor Segmentation (BraTS-METS) Challenge 2023: Brain Metastasis Segmentation on Pre-treatment MRI.

The translation of AI-generated brain metastases (BM) segmentation into clinical practice relies heavily on diverse, high-quality annotated medical imaging datasets. The BraTS-METS 2023 challenge has gained momentum for testing and benchmarking algorithms using rigorously annotated internationally compiled real-world datasets. This study presents the results of the segmentation challenge and characterizes the challenging cases that impacted the performance of the winning algorithms.

Discriminant Analysis of the Prognostic Factors for Hearing Outcomes in Patients with Idiopathic Sudden Sensorineural Hearing Loss.

Background: This study aims to determine and assess prognostic variables that might affect the hearing result in patients with idiopathic sudden sensorineural hearing loss following intratympanic steroid injection.

Methods: In total, 190 patients with idiopathic sudden sensorineural hearing loss received intratympanic steroid injection. Two hearing indices (recovery and nonrecovery) will be analyzed as dependent variables; patient's age, time period between the onset of hearing loss and treatment, initial level of hearing (hearing loss pre), type of audiogram curve (upsloping, downsloping, and flat), presence of vertigo, presence of tinnitus, and diabetes) will be analyzed as prognostic factor variables.

Promotion of a synthetic degradation of activated STAT6 by PARP-1 inhibition: roles of poly(ADP-ribosyl)ation, calpains and autophagy.

Background: We reported that PARP-1 regulates genes whose products are crucial for asthma, in part, by controlling STAT6 integrity speculatively through a calpain-dependent mechanism. We wished to decipher the PARP-1/STAT6 relationship in the context of intracellular trafficking and promoter occupancy of the transcription factor on target genes, its integrity in the presence of calpains, and its connection to autophagy.

Methods: This study was conducted using primary splenocytes or fibroblasts derived from wild-type or PARP-1 mice and Jurkat T cells to mimic Th2 inflammation.

Are direct oral anticoagulants preferable to warfarin for the treatment of left ventricular thrombi? A Bayesian meta-analysis of randomized controlled trials.

Background: There is no clear consensus on the optimal choice of anticoagulant in patients with left ventricular thrombi (LVT). Given the potentially fatal complications associated with this disease entity, we performed a systematic review and meta-analysis of recent randomized clinical trials (RCTs) to synthesize the latest evidence on this topic.

Methods: We performed a comprehensive search of electronic databases to identify RCTs comparing warfarin to direct oral anticoagulants (DOACs) in patients with LVT.

Comparison between the endoscopic scores of bolgerization versus partial resection of the middle turbinate for management of the postoperative lateralization in the early follow-up period after endoscopic frontal sinusotomy: A randomized controlled study.

Background: Frontal sinusotomy is a challenging procedure that needs meticulous handling due to its unique anatomical position. Postoperative middle turbinate lateralization is critical comorbidity for the success rate, and many techniques are adopted to prevent it. The study aimed to compare the effect of middle turbinate bolgerization and partial resection on the postoperative endoscopic scores and assess their impact on the middle meatus and the frontal recess outcome.

The prognostic variables affecting the frontal sinusotomy patency outcome and how to manage: A prospective study.

Objectives: The study aimed to assess the factors affecting the frontal sinus patency after endoscopic frontal sinusotomy.

Design: A prospective cohort study.

Setting: Tertiary centre hospital.

The impact of bolgerization versus partial resection of the middle turbinate on frontal sinusotomy patency outcome: A randomised controlled study.

Objectives: This study aimed to compare the effects of middle turbinate resection vs bolgerization on the incidence of middle meatus synechia and their prognostic value on the patency outcomes after frontal sinusotomy.

Design: A randomised controlled study.

Setting: Tertiary centre hospital.

Acute effect of inhaled iloprost on exercise dynamic hyperinflation in COPD patients: A randomized crossover study.

Background And Objective: We tested whether the prostacyclin analog inhaled iloprost modulates dead space, dynamic hyperinflation (DH), and systemic inflammation/oxidative stress during maximal exercise in subjects with chronic obstructive pulmonary disease (COPD) who were not selected based on pulmonary hypertension (PH).

Methods: Twenty-four COPD patients with moderate-severe obstruction (age 59 ± 7 years, FEV 53 ± 13% predicted) participated in a randomized, double-blind, placebo-controlled crossover trial. Each subject received a single nebulized dose of 5.

The preoperative radiological findings associated with failure of frontal sinusotomy: A prospective study.

Objectives: The study aimed to assess the association between the preoperative CT findings and the patency outcome of the frontal sinus after endoscopic frontal sinusotomy in the early follow-up period.

Design: A prospective cohort study.

Setting: Tertiary hospital centre.

Targeting PARP-1 with metronomic therapy modulates MDSC suppressive function and enhances anti-PD-1 immunotherapy in colon cancer.

Background: Poly(ADP-ribose) polymerase (PARP) inhibitors (eg, olaparib) are effective against BRCA-mutated cancers at/near maximum tolerated doses by trapping PARP-1 on damaged chromatin, benefitting only small patient proportions. The benefits of targeting non-DNA repair aspects of PARP with metronomic doses remain unexplored.

Methods: Colon epithelial cells or mouse or human bone marrow (BM)-derived-myeloid-derived suppressor cells (MDSCs) were stimulated to assess the effect of partial PARP-1 inhibition on inflammatory gene expression or immune suppression.

Combined preoperative HRCT parameters for prediction of round window visibility in pediatric cochlear implant patient.

Objective: To evaluate the add value of combined analysis of high resolution computed tomography (HRCT) temporal bone parameters in accurate prediction of round window (RW) visibility through posterior tympanotomy.

Patients And Methods: a retrospective observational study was held in a tertiary center, conducted on 45 cochlear implant pediatric candidates between January 2017 and September 2019. Candidates were referred for CT temporal bone.

PARP-1 Is Critical for Recruitment of Dendritic Cells to the Lung in a Mouse Model of Asthma but Dispensable for Their Differentiation and Function.

Dendritic cells (DCs) are critical in asthma and many other immune diseases. We previously demonstrated a role for PARP-1 in asthma. Evidence on PARP-1 playing a role in Th2-associated DC function is not clear.

Microparticles in systemic sclerosis: Potential pro-inflammatory mediators and pulmonary hypertension biomarkers.

Background And Objective: Endothelial microparticles (EMP) are submicron vesicles released from endothelial cells. We aimed to determine the utility of EMP as biomarkers of pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) patients and the pathogenic role of microparticles (MP) in vascular inflammation.

Methods: Levels of EMP (CD144+, CD31+, CD62E+ and CD143+) were compared between three groups (10 SSc patients with PAH, 10 SSc patients without pulmonary hypertension (no-PH) and 10 healthy age- and sex-matched controls).

Sulfated non-anticoagulant heparin blocks Th2-induced asthma by modulating the IL-4/signal transducer and activator of transcription 6/Janus kinase 1 pathway.

Background: The efficacy of heparins and low-MW-heparins (LMWH) against human asthma has been known for decades. However, the clinical utility of these compounds has been hampered by their anticoagulant properties. Much effort has been put into harnessing the anti-inflammatory properties of LMWH but none have been used as therapy for asthma.