Coffee, PI3K signaling pathway, and prostate cancer: a prospective study in the Health Professionals Follow-up Study.

BACKGROUND: Higher coffee intake has been associated with reduced risk of prostate cancer, particularly aggressive forms. The activation of the PI3K signaling pathway plays an important role in prostate carcinogenesis. OBJECTIVE: To evaluate associations between pre-diagnostic coffee intake and a PI3K activation score, the expression/presence of PI3K regulators, and downstream effectors in tumor tissue from men with prostate cancer in the Health Professionals Follow-up Study, a prospective cohort study conducted in the US. DESIGN: A case-only study design was applied. Coffee intake was assessed using validated food frequency questionnaires completed in 1986 and every four years thereafter until prostate cancer diagnosis. PARTICIPANTS/SETTING: Study participants comprised 1,242 men diagnosed with prostate cancer from 1986 to 2009 and with tumor markers assessed from tissue microarrays constructed from tumor specimens. MAIN OUTCOME MEASURES: The outcomes include the PI3K activation score; expression of insulin receptor and IGF1 receptor; angiogenesis markers; and presence of the tumor suppressor PTEN, chronic and acute inflammation, simple atrophy, and post-atrophic hyperplasia. STATISTICAL ANALYSES PERFORMED: Multivariable linear or logistic regression was conducted to estimate associations between coffee intake and tumor marker expression/presence. RESULTS: Among coffee drinkers (86.6% of the population), median (25th-75th) coffee intake was 2 (1-3) cups/day. The associations between coffee consumption and the tumor markers of interest were generally weak with modest precision. When comparing men who drank >3 cups/day of coffee with nondrinkers, the absolute percent difference in the PI3K activation score and angiogenesis markers ranged from 0.6% to 3.6%. The odds ratios for PTEN loss, IGF1 receptor and insulin receptor expression, and presence of chronic and acute inflammation, simple atrophy, and post-atrophic hyperplasia also were not statistically significant, were imprecise, and ranged from 0.82 to 1.58. CONCLUSIONS: Coffee intake was not observed to be associated with PI3K activation, related regulators, and several effectors in prostate tumor tissue. Studies exploring alternative pathways or earlier steps in carcinogenesis are needed to investigate the underlying mechanisms of the coffee and prostate cancer association.

A Central Auditory Test reveals differences between drug treatment regimens in adults living with HIV.

OBJECTIVE: This exploratory study examined whether central auditory tests show differences between people living with HIV (PLWH) treated with two predominant antiretroviral drug therapy (ART) regimens. DESIGN: Cross-sectional. STUDY SAMPLE: 253 PLWH (mean age 39.8 years) from the Shanghai Public Health Clinical Centre, China. METHODS: The Hearing in Noise Test speech reception threshold (SRT) assessed central auditory function and the Montreal Cognitive Assessment (MoCA) assessed cognition. The relationship between ART regimen and SRT was evaluated with multivariable linear regression incorporating age, HIV duration, and peripheral hearing ability. Multivariable logistic regression was used to ascertain if SRT and ART regimen predicted MoCA impairment. RESULTS: The two predominant ART regimens differed by one drug (zidovudine or tenofovir). Participants taking the zidovudine-containing regimen had poorer SRT performance (p=.012) independent of age and hearing thresholds. MoCA scores did not differ between drug regimens, but a negative relationship was found between SRT and MoCA impairment (p=.048). CONCLUSIONS: ART regimens differed in their association with central auditory test performance likely reflecting neurocognitive changes in PLWH taking the zidovudine-containing regimen. Central auditory test performance also marginally predicted cognitive impairment, supporting further assessment of central auditory tests to detect neurocognitive deficits in PLWH.

Unexplained multi-sensory neuropathy syndrome in young Tanzanian adults.

BACKGROUND: A unique syndrome affecting young adults of unexplained hearing loss often associated with uncorrectable poor visual acuity and lower extremity numbness is endemic in Dar es Salaam. This study characterized the hearing loss, associated it with other symptoms, and gathered information on potential causes. METHODS: Forty-seven patients (23 men, 24 women) <40 years old with a symptom consistent with the syndrome, negative syphilis test, and no head injury history were recruited from Muhimbili National Hospital. 18 controls (10 men, 8 women) were recruited from the same neighborhoods as patients. Hearing ability and cochlear outer hair cell function (distortion-product otoacoustic emissions (DPOAEs)) were assessed, as were visual acuity and color vision. Peripheral neuropathy was evaluated using the Michigan Neuropathy Screening Instrument (MNSI), and physical examination. Blood C-reactive protein levels and toenail trace metal concentrations were measured. Environmental exposures were elicited using a questionnaire. Patients with at least two of the following signs were defined as having the syndrome: poor hearing with normal DPOAEs, vision not correctable to better than 20/30, or a MNSI score greater than 4. RESULTS: 29 participants met the case definition. CRP levels did not differ between groups but manganese, cobalt and tin levels were each greater in the cases than controls. No other environmental exposure differences were noted. CONCLUSIONS: Toenail manganese, cobalt, and tin levels were higher in those with the syndrome. These metals are potential neurotoxins suggesting a possible environmental origin for this unique and debilitating syndrome.

Urinary Calcium for Tracking Bone Loss and Kidney Stone Risk in Space.

INTRODUCTION: Urinary calcium (Uca) levels in space reflect bone loss and kidney stone risk and could be measured using portable devices. This project evaluated the repeatability of Uca measurements to assess how many repeated measurements would be needed to detect significant urinary calcium elevations in space.METHODS: A total of six subjects collected 24-h urine samples weekly for 8 wk and took 500 mg of oral calcium carbonate and 400 IU of vitamin D daily in week 7 and 8. Uca concentration was analyzed using a calcein-based system. The effect of the intake of calcium and vitamin D on Uca levels and the correlation between first void concentration and 24-h mass were assessed with linear mixed effect models. The reproducibility coefficient (RPC) for Uca was determined using Bland-Altman analysis on pairs of measurements at different time points.RESULTS: Oral supplementation did not significantly affect 24-h mass. First void concentration correlated with 24-h mass. The 24-h mass RPCs were 167.0, 116.8, and 108.1 mg for 1-, 2-, and 3-wk average measurements. First void concentration RPCs were 90.6, 76.6, and 72.8 mg L1. Skylab astronauts 24-h mass increased by 88.9 76.0, 123.5 58.3, 142.2 56.5, and 159.9 83.4 mg after 1, 2, 3, and 4 wk in flight.DISCUSSION: Averaging multiple Uca measurements reduced variability effectively and allowed increases likely to be seen in space to be detected. Consecutive Uca measurements could be tracked over time in space to assess the effectiveness of the countermeasure program. First void concentration could potentially be used rather than 24-h collections.Ren J, Stankovic AS, Knaus DA, Phillips SD, Kynor DB, Buckey JC. Urinary calcium for tracking bone loss and kidney stone risk in space. Aerosp Med Hum Perform. 2020; 91(9):689696.

Understanding the effect of anthocyanins extracted from purple sweet potatoes on alcohol-induced liver injury in mice.

Anthocyanins as antioxidants are potential to protect liver from alcoholic damage, but might be pro-oxidants under certain conditions. In this study, twelve purple sweet potatoes anthocyanins (PSPA) were isolated and their effects on alcohol-induced liver injury were studied. These PSPA were rich in cyanidin derivatives and fed to male C57BL/6 mice as colorants in alcoholic drink with low, median, or high dosages PSPA i.e. 50, 100, or 300 mg/kg·BW·d. Compared to the alcohol group, the median-dose PSPA showed a clear improvement in the liver indexes/histology, serum ALT level, oxidative stress status, and even a recovery to the normal level, however the high dose PSPA promoted the liver injury via a pro-oxidant effect, as reflected by increased malondialdehyde (MDA) content and decreased GSH level. The results suggested that cyanidin derivatives with an ortho-hydroxyl structure on B-ring might promote the oxidative stress of alcohol-induced liver injury at high doses as a pro-oxidant.