Brain cancer remains among the most lethal malignancies worldwide, with approximately 321,476 new cases and 248,305 deaths reported globally in 2022. The treatment of malignant brain tumors presents substantial clinical challenges, primarily due to their resistance to standard therapeutic approaches. Despite decades of intensive research, effective treatment strategies for brain cancer are still lacking. Nuclear receptors (NRs), a superfamily of ligand-activated transcription factors, regulate a broad range of physiological processes including metabolism, immunity, stress response, reproduction, and cellular differentiation. Increasing evidence highlights the involvement of NRs in oncogenesis, with several members demonstrating altered expression and function in brain tumors. Aberrations in NR signaling, encompassing receptors such as androgen receptors, estrogen receptors, estrogen-related receptors, glucocorticoid receptors, NR subfamily 4 group A, NR subfamily 1 group D member 2, NR subfamily 5 group A member 2, NR subfamily 2 group C member 2, liver X receptors, peroxisome-proliferator activated receptors, progesterone receptors, retinoic acid receptors, NR subfamily 2 group E member 1, thyroid hormone receptors, vitamin D receptors, and retinoid X receptors, have been implicated in promoting hallmark malignant phenotypes, including enhanced survival, proliferation, invasion, migration, metastasis, and resistance to therapy. This review aims to explore the roles of key NRs in brain cancer, with an emphasis on their prognostic significance, and to evaluate the therapeutic potential of targeting these receptors using selective agonists or antagonists.
Humans ; Brain Neoplasms/drug therapy* ; Receptors, Cytoplasmic and Nuclear/metabolism* ; Animals ; Signal Transduction/physiology*

INTRODUCTION: This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of adjunct systemic corticosteroid therapy in patients admitted to the intensive care unit (ICU) with bacterial community-acquired pneumonia (CAP). METHOD: We searched MEDLINE, Embase and the Cochrane Library to identify randomised controlled trials (RCTs) published from the databases' inception to February 2024. All RCTs evaluating the effect of systemic corticosteroids on mortality, compared to standard of care among adult bacterial CAP patients admitted to ICU were included. Bayesian meta-analysis was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Independent authors reviewed each study for eligibility, extracted data and assessed risk of bias in duplicate, with discrepancies referred to senior reviewers. RESULTS: A total of 6 RCTs comprising 1585 patients were included for analysis. In ICU patients with severe CAP who were treated with corticosteroids, there was no significant reduction in hospital mortality (risk ratio [RR] 0.70, 95% confidence interval [CI] 0.39-1.14, certainty of evidence: ⊕⊕⊝⊝ low) or all-cause mortality (RR 0.68, 95% CI 0.34-1.22, ⊕⊕⊝⊝ low) compared with placebo. The use of corticosteroids showed a significant reduction in mechanical ventilation post-intervention (RR 0.58, 95% CI 0.37-0.86, ⊕⊕⊕⊕ high) compared with placebo. In a subgroup analysis of patients treated with hydrocortisone, hospital mortality was significantly reduced (RR 0.45, 95% CI 0.20-0.88, ⊕⊕⊝⊝ low) compared with placebo. There was no significant increase in gastrointestinal bleeding, secondary infections or hyperglycaemia in patients treated with corticosteroids. CONCLUSION Corticosteroids significantly reduced mechanical ventilation requirements, and hydrocor-tisone significantly reduced hospital mortality. Further work is required to determine whether other corticosteroids reduce mortality among ICU patients with CAP.
Humans ; Adrenal Cortex Hormones/therapeutic use* ; Bayes Theorem ; Community-Acquired Infections/mortality* ; Critical Illness ; Hospital Mortality ; Intensive Care Units ; Pneumonia, Bacterial/mortality* ; Randomized Controlled Trials as Topic ; Respiration, Artificial

Humans ; COVID-19 ; Pandemics ; Grief ; SARS-CoV-2

Depression ; Depressive Disorder, Major ; Employment ; Humans

Coccidiosis is a major recurring problem in the poultry industry and is caused by infection of one or more of the seven Eimeria species known to infect chickens, with Eimeria tenella among the best studied and economically important. Studies on the genetic diversity of E. tenella strains is essential for the development of universally acceptable diagnostic markers and vaccines against the disease. Eimeria tenella internal transcribed spacer-1 (ITS-1) and apical membrane antigen-1 (AMA-1) sequences from different parts of the world are available in the public domain and therefore provide suitable comparative markers for genetic diversity study. In this study, the ITS-1 and AMA-1 sequence diversity of two local E. tenella strains, namely EtNSN6 and EtSGR6 were characterized. Both ITS-1 and AMA-1 sequences for EtNSN6 and EtSGR6 were retrieved by mapping to their respective genome sequences generated using next generation sequencing. Multiple sequence alignment of the ITS-1 and AMA-1 sequences with selected homologous sequences revealed the presence of a total of five and 13 single nucleotide polymorphisms (SNPs) respectively. All SNPs appeared to occur at random and did not show any unique pattern based on geographical regions while no insertions and deletions (indels) was found to occur in the aligned sequences. However, unique bases that defined certain strains were detected. Phylogenetics analyses performed with Maximum Parsimony (MP) and Maximum Likelihood (ML) methods revealed similar topology for the internal groups with all the E. tenella ITS-1 and AMA-1 sequences grouped in the same clade supported by high bootstrap confidence. This confirmed that both EtNSN6 and EtSGR6 samples are E. tenella strains. Sequence comparison and phylogenetics analyses further suggest the possibility of low genetic diversity among E. tenella strains.

COVID-19/psychology* ; Global Health/statistics & numerical data* ; Health Personnel/statistics & numerical data* ; Humans ; Mental Disorders/etiology* ; Mental Health/statistics & numerical data* ; Occupational Diseases/psychology*

: Multiparametric MRI (mpMRI) of the prostate is recently becoming more and more utilized in the detection of prostate cancer. Studies have shown that a higher PIRADS score correlated to a higher chance of obtaining a clinically significant prostate cancer but few studies have correlated PIRADS score to a specific Gleason score. OBJECTIVE: This study aimed to determine the concordance of PIRADS score to the Gleason score result of MRI ultrasound fusion-guided prostate biopsy. METHODS: All patients who had at least a PIRADS 2 lesion on mpMRI and underwent MRI ultrasound fusion-guided biopsy of the prostate from August 2018 up to November 2019 at St. Luke’s Medical Center, Global City were included in the study. An ambispective collection of data was done until the ideal sample size of greater than 100 positive lesions was obtained, in order to derive concordance rate. RESULTS: One hundred and sixty-two patients were included in the study with a total of 212 lesions analyzed. Forty three percent were benign while 57% were found to be malignant. PIRADS 2 lesions had zero high grade cancers, and the percentage steadily increased with 37.8% of PIRADS lesions considered high grade. Concordance was computed to be 0.38 showing a fair, direct concordance between PIRADS and Gleason score with significant result (p<0.05). CONCLUSION A result of PIRADS 4 or 5 lesion on mpMRI will have a higher urgency of doing a prostate biopsy and subsequent management to prevent unfavorable outcomes as opposed to PIRADS 3 lesions.