Compound heterozygous TMEM67 biallelic variants including a novel frameshift mutation in two Filipino adolescent siblings with Joubert syndrome.

Joubert Syndrome (JS) is a congenital cerebellar ataxia typically inherited in an autosomal recessive pattern, although rare X-linked inheritance can occur. It is characterized by hypotonia evolving into ataxia, global developmental delay, oculomotor apraxia, breathing dysregulation, and multiorgan involvement. To date, there are 40 causative genes implicated in JS, all of which encode proteins of the primary cilium.

Tigecycline-Induced Acute Pancreatitis with Electrocardiogram Changes in Renal Insufficiency Elderly.

Background: The prevalence of multidrug-resistant and extensively drug-resistant pathogens has led to increased reliance on broad-spectrum antimicrobials, such as tigecycline. This medicine is commonly used to treat complicated skin and intraabdominal infections as well as community-acquired pneumonia. However, the increasing use of tigecycline has been linked to serious complications, including acute pancreatitis.

Evaluating the Impact of Multimodal Prehabilitation with High Protein Oral Nutritional Supplementation (HP ONS) with Beta-Hydroxy Beta-Methylbutyrate (HMB) on Sarcopenic Surgical Patients-Interim Analysis of the HEROS Study.

Background: Multimodal prehabilitation programs, which may incorporate nutritional supplementation and exercise, have been developed to combat sarcopenia in surgical patients to enhance post-operative outcomes. However, the optimal regime remains unknown. The use of beta-hydroxy beta-methylbutyrate (HMB) has beneficial effects on muscle mass and strength.

Targeting P4HA1 promotes CD8 T cell progenitor expansion toward immune memory and systemic anti-tumor immunity.

Successful immunotherapy relies on both intratumoral and systemic immunity, which is yet to be achieved for most patients with cancer. Here, we identify P4HA1, encoding prolyl 4-hydroxylase 1, as a crucial regulator of CD8 T cell differentiation strongly upregulated in tumor-draining lymph nodes (TDLNs) and hypoxic tumor microenvironment. P4HA1 accumulates in mitochondria, disrupting the tricarboxylic acid (TCA) cycle through aberrant α-ketoglutarate and succinate metabolism, promoting mitochondria unfitness and exhaustion while suppressing progenitor expansion.