Association of TP53 Single Nucleotide Polymorphisms with Prostate Cancer in a Racially Diverse Cohort of Men.

Growing evidence indicates the involvement of a genetic component in prostate cancer (CaP) susceptibility and clinical severity. Studies have reported the role of germline mutations and single nucleotide polymorphisms (SNPs) of TP53 as possible risk factors for cancer development. In this single institutional retrospective study, we identified common SNPs in the TP53 gene in AA and CA men and performed association analyses for functional TP53 SNPs with the clinico-pathological features of CaP. The SNP genotyping analysis of the final cohort of 308 men (212 AA; 95 CA) identified 74 SNPs in the TP53 region, with a minor allele frequency (MAF) of at least 1%. Two SNPs were non-synonymous in the exonic region of TP53: rs1800371 (Pro47Ser) and rs1042522 (Arg72Pro). The Pro47Ser variant had an MAF of 0.01 in AA but was not detected in CA. Arg72Pro was the most common SNP, with an MAF of 0.50 (0.41 in AA; 0.68 in CA). Arg72Pro was associated with a shorter time to biochemical recurrence (BCR) (p = 0.046; HR = 1.52). The study demonstrated ancestral differences in the allele frequencies of the TP53 Arg72Pro and Pro47Ser SNPs, providing a valuable framework for evaluating CaP disparities among AA and CA men.

Presentation of Caffeine Intoxication in an Active Duty Service Member Originally Believed to Have a Psychotic Disorder.

Caffeine has the highest use of any psychoactive substance worldwide and is highly appealing to military personnel who are required to work the long, grueling hours necessary to complete a mission. However, published reports of caffeine intoxication in the medical literature are rare. Individuals undergoing military training experience long work hours in a stressful environment. These conditions can make various caffeine supplements enticing. However, most energy drinks contain multiple serving sizes, and supplements are often packaged in large containers, increasing individuals' risk of caffeine overconsumption and intoxication. Additionally, young adults in stressful environments are the classic demographic in which the first presentation of a psychiatric illness, such as psychotic disorder, occurs. Interestingly, many of the presenting signs and symptoms, including agitation, restlessness, insomnia, tremors, tachycardia, and psychomotor agitation, are the same in both diagnoses. This stresses the importance of differentiating caffeine intoxication from a psychotic disorder. We present a novel case of an active-duty Service member who presented to the emergency room with symptoms concerning the psychotic disorder. After a more detailed history was acquired, caffeine intoxication became more likely and was ultimately treated. We discuss the overlap in presentation and thus difficulty in differentiating caffeine intoxication from a psychotic disorder.

The Great Imitator: Latent Neurosyphilis Revealed After Initiation of the Immunosuppressive Drug Secukinumab.

Syphilis is a multi-organ system bacterial infection caused by the bacterium Treponema pallidum. Syphilis can advance through four clinical stages: primary, secondary, latent, and tertiary. Once in the tertiary stage, mortality is seen in up to 58% of individuals. Here, we present a case of latent neurosyphilis manifesting after initiation of the immunosuppressive medication secukinumab, a monoclonal antibody that antagonizes interleukin-17A. A 66-year-old male with type II diabetes mellitus, hyperlipidemia, and rheumatoid arthritis presented to the emergency department for a right lower quadrant abdominal cellulitis at the site of his insulin pump. On examination, a non-blanching papular rash on the palms and soles with several scaling papules was discovered. No visible pustules, oral lesions, or perirectal lesions were seen. Neurological examination was noncontributory. His past medical history revealed initiation of secukinumab for the management of rheumatoid arthritis two months prior to presentation. The rash developed six weeks after starting secukinumab. Basic laboratory tests, including a complete blood count, thyroid panel, renal function panel, fasting blood glucose, electrolytes, and C-reactive protein, were within normal limits. A hepatic panel revealed mildly elevated alkaline phosphatase, alanine transaminase, and erythrocyte sedimentation rate Westergren level. Laboratory tests for hepatitis B, hepatitis C, HIV-1, Chlamydia trachomatis, and Neisseria gonorrhoeae all returned negative. A rapid plasma reagin (RPR) titer returned positive at 1:128, and a serum Treponema pallidum Ab returned reactive. Lumbar puncture serologies demonstrated a positive Venereal Disease Research Laboratory (VDRL) test. The patient was diagnosed with latent neurosyphilis and started on intravenous crystalline penicillin G for three weeks. A thorough history, comprehensive physical examination, and basic workup should be performed in any individual prior to immunosuppressive medication initiation. On initial presentation, our patient had an isolated rash on the palms and soles, which is classical for secondary syphilis. The specific manifestations seen in syphilis depend upon the timing, site, and immune status of the individual. Due to its ability to have a variety of presentations, syphilis should always remain on the differential for any physician caring for immunocompromised individuals. Again, initiation of immunosuppressive medications, such as the monoclonal antibody secukinumab, can result in the reactivation of previously dormant infections. As physicians, we must carefully screen our patients prior to initiating immunosuppressive agents to prevent disease reactivation.

The effects of acute and repeated methylenedioxypyrovalerone (MDPV) administration on striatal transcriptome networks in male long evans rats.

The psychoactive drug methylenedioxypyrovalerone (MDPV) elicits feelings of euphoria and hyperexcitability, but can also result in paranoia, agitation, and depression by unknown mechanisms. We identified molecular networks in the rat striatum that were affected by single or repeated exposure to MDPV. Male Long Evans rats were injected with either saline or MDPV (1 mg/kg) (single or repeated MDPV) over 5 days. To distinguish the effects of repeated MDPV from a single exposure, an additional group received saline over 4 days and then MDPV on the 5th day. Twenty-four hours after the final injection, the left dorsal striatum was processed for transcriptomics. The transcriptome response was subtle after 24 h, and a single gene passed an FDR correction (LOC103691845) following repeated MDPV treatment. Gene set and subnetwork enrichment analyses were conducted to improve data interpretation from a network perspective. Consistent with the mode of action of MDPV, networks related to the nigrostriatal dopaminergic system were altered in the rat striatum. Transcriptional networks related to cognition, short and long-term memory, and synaptic transmission were over-represented in the striatum of rats repeatedly injected with MDPV. This study identifies potential transcriptional networks altered by single or repeated MDPV exposure, which can be interrogated further to elucidate molecular mechanisms underlying cathinone abuse.