Trichomonas vaginalis infection and prostate-specific antigen concentration: Insights into prostate involvement and prostate disease risk.

BACKGROUND: The protist Trichomonas vaginalis causes a common, sexually transmitted infection and has been proposed to contribute to the development of chronic prostate conditions, including benign prostatic hyperplasia and prostate cancer. However, few studies have investigated the extent to which it involves the prostate in the current antimicrobial era. We addressed this question by investigating the relation between T. vaginalis antibody serostatus and serum prostate-specific antigen (PSA) concentration, a marker of prostate infection, inflammation, and/or cell damage, in young, male, US military members. METHODS: We measured T. vaginalis serum IgG antibodies and serum total PSA concentration in a random sample of 732 young, male US active duty military members. Associations between T. vaginalis serostatus and PSA were investigated by linear regression. RESULTS: Of the 732 participants, 341 (46.6%) had a low T. vaginalis seropositive score and 198 (27.0%) had a high score, with the remainder seronegative. No significant differences were observed in the distribution of PSA by T. vaginalis serostatus. However, slightly greater, nonsignificant differences were observed when men with high T. vaginalis seropositive scores were compared with seronegative men, and when higher PSA concentrations were examined (≥0.70 ng/mL). Specifically, 42.5% of men with high seropositive scores had a PSA concentration greater than or equal to 0.70 ng/mL compared with 33.2% of seronegative men (adjusted P = .125). CONCLUSIONS: Overall, our findings do not provide strong support for prostate involvement during T. vaginalis infection, although our suggestive positive findings for higher PSA concentrations do not rule out this possibility entirely. These suggestive findings may be relevant for prostate condition development because higher early- to mid-life PSA concentrations have been found to predict greater prostate cancer risk later in life.

Neurotoxicity Associated with Traumatic Brain Injury, Blast, Chemical, Heavy Metal and Quinoline Drug Exposure.

Chronic, excessive exposure, and accumulation of neurotoxic agents such as heavy metals (lead, mercury, cadmium), mefloquine (Lariam), and food additives such as monosodium glutamate and aspartame cause neurotoxicity and brain damage. This chemical-induced brain damage closely resembles the pathophysiology of classical traumatic brain injury with decreased cognitive function, neurodegeneration, and increased psychiatric manifestations (depression, anxiety, sleep disturbances, and irritability). Current evidence supports a strong causal relationship between military-related exposure to specific neurotoxins, and the development of serious medical conditions and higher rates of suicide among service members. To address this current deficit in military health care, it is recommended that efficacious, nontoxic, neuroprotective, and neuroregenerative agents such as highly bioavailable magnesium, nutritional lithium, zinc, selenium, boron, ascorbate, tocopherols, heavy metal chelators, and glutathione precursors such as N-acetyl-cysteine be immediately used as a "protective shield" and to support critical healing processes in the brain and nervous system.

Sustained influence of infections on prostate-specific antigen concentration: An analysis of changes over 10 years of follow-up.

BACKGROUND: To extend our previous observation of a short-term rise in prostate-specific antigen (PSA) concentration, a marker of prostate inflammation and cell damage, during and immediately following sexually transmitted and systemic infections, we examined the longer-term influence of these infections, both individually and cumulatively, on PSA over a mean of 10 years of follow-up in young active duty U.S. servicemen. METHODS: We measured PSA in serum specimens collected in 1995-7 (baseline) and 2004-6 (follow-up) from 265 men diagnosed with chlamydia (CT), 72 with gonorrhea (GC), 37 with non-chlamydial, non-gonococcal urethritis (NCNGU), 58 with infectious mononucleosis (IM), 91 with other systemic or non-genitourinary infections such as varicella; and 125-258 men with no infectious disease diagnoses in their medical record during follow-up (controls). We examined the influence of these infections on PSA change between baseline and follow-up. RESULTS: The proportion of men with any increase in PSA (>0 ng/mL) over the 10-year average follow-up was significantly higher in men with histories of sexually transmitted infections (CT, GC, and NCNGU; 67.7% vs 60.8%, P = 0.043), systemic infections (66.7% vs 54.4%, P = 0.047), or any infections (all cases combined; 68.5% vs 54.4%, P = 0.003) in their military medical record compared to controls. CONCLUSIONS: While PSA has been previously shown to rise during acute infection, these findings demonstrate that PSA remains elevated over a longer period. Additionally, the overall infection burden, rather than solely genitourinary-specific infection burden, contributed to these long-term changes, possibly implying a role for the cumulative burden of infections in prostate cancer risk.

Insight into infection-mediated prostate damage: Contrasting patterns of C-reactive protein and prostate-specific antigen levels during infection.

BACKGROUND: To investigate mechanisms underlying our previous observation of a large rise in serum prostate-specific antigen, a marker of prostate pathology, during both sexually transmitted and systemic infections, we measured serum high-sensitivity C-reactive protein (hsCRP), a marker of systemic inflammation, in our previous case-control study of young, male US military members and compared our findings to those for PSA. METHODS: We measured hsCRP before and during infection for 299 chlamydia, 112 gonorrhea, and 59 non-chlamydial, non-gonococcal urethritis (NCNGU) cases; before and after infection for 55 infectious mononucleosis (IM) and 90 other systemic/non-genitourinary cases; and for 220-256 controls. RESULTS: Only gonorrhea cases were significantly more likely to have a large hsCRP rise (≥1.40 mg/L or ≥239%) during infection than controls (P < 0.01). However, gonorrhea, IM, and other systemic/non-genitourinary cases were more likely to have a rise of any magnitude up to one year post-diagnosis than controls (p = 0.038-0.077). CONCLUSIONS: These findings, which differ from those for PSA, suggest distinct mechanisms of elevation for hsCRP and PSA, and support both direct (eg, prostate infection) and indirect (eg, systemic inflammation-mediated prostate cell damage) mechanisms for PSA elevation. Future studies should explore our PSA findings further for their relevance to both prostate cancer screening and risk.

Stellate Ganglion Block in the Treatment of Post-traumatic Stress Disorder: A Review of Historical and Recent Literature.

Concerns over the rising prevalence of post-traumatic stress disorder (PTSD), particularly among military service members returning from combat, and over barriers that hinder individuals from seeking out or adhering to standard therapies have contributed to interest in alternative therapies for the disorder. A novel alternative therapy for PTSD-stellate ganglion block (SGB)-may be considered lacking in formal evidence of efficacy despite having shown considerable promise. This review of the recent and historical literature related to SGB finds evidence of substantial beneficial psychiatric effects and substantiates that this fast-acting, somatic treatment may provide positive results for patients with PTSD and may reduce barriers to therapy, particularly among military populations.

Infectious mononucleosis, other infections and prostate-specific antigen concentration as a marker of prostate involvement during infection.

Although Epstein-Barr virus has been detected in prostate tissue, no associations have been observed with prostate cancer in the few studies conducted to date. One possible reason for these null findings may be use of cumulative exposure measures that do not inform the timing of infection, i.e., childhood versus adolescence/early adulthood when infection is more likely to manifest as infectious mononucleosis (IM). We sought to determine the influence of young adult-onset IM on the prostate by measuring prostate-specific antigen (PSA) as a marker of prostate inflammation/damage among U.S. military members. We defined IM cases as men diagnosed with IM from 1998 to 2003 (n = 55) and controls as men without an IM diagnosis (n = 255). We selected two archived serum specimens for each participant, the first collected after diagnosis for cases and one randomly selected from 1998 to 2003 for controls (index), as well as the preceding specimen (preindex). PSA was measured in each specimen. To explore the specificity of our findings for prostate as opposed to systemic inflammation, we performed a post hoc comparison of other infectious disease cases without genitourinary involvement (n = 90) and controls (n = 220). We found that IM cases were more likely to have a large PSA rise than controls (≥ 20 ng/mL: 19.7% versus 8.8%, p = 0.027; ≥ 40% rise: 25.7% versus 9.4%, p = 0.0021), as were other infectious disease cases (25.7% versus 14.0%, p = 0.020; 27.7% versus 18.0%, p = 0.092). These findings suggest that, in addition to rising because of prostate infection, PSA may also rise because of systemic inflammation, which could have implications for PSA interpretation in older men.

Psychiatric effects of malaria and anti-malarial drugs: historical and modern perspectives.

The modern medical literature implicates malaria, and particularly the potentially fatal form of cerebral malaria, with a risk of neurocognitive impairment. Yet historically, even milder forms of malaria were associated in the literature with a broad range of psychiatric effects, including disorders of personality, mood, memory, attention, thought, and behaviour. In this article, the history of psychiatric effects attributed to malaria and post-malaria syndromes is reviewed, and insights from the historical practice of malariotherapy in contributing to understanding of these effects are considered. This review concludes with a discussion of the potentially confounding role of the adverse effects of anti-malarial drugs, particularly of the quinoline class, in the unique attribution of certain psychiatric effects to malaria, and of the need for a critical reevaluation of the literature in light of emerging evidence of the chronic nature of these adverse drug effects.

The timeliness of the US military response to the 2014 Ebola disaster: a critical review.

In the face of an unprecedented epidemic of Ebola Virus Disease, in September 2014, the US military began sending thousands of personnel to Liberia and supporting areas in Senegal in its largest deployment to the African continent in over two decades. In this review, media reports, published photographs and official statements are evaluated and summarized to identify and describe key time points in the US military response. Specific events include the initial establishment of the Monrovia Medical Unit and the buildup of forces for the expanded mission, which involved enhancement of laboratory testing capacity, construction of Ebola Treatment Units, and training of health care workers. The review concludes with a discussion and critical evaluation of the timeliness of this US military response in the context of the original expectations of the humanitarian community and government officials.

Population estimates of undocumented incident traumatic brain injuries among combat-deployed US military personnel.

OBJECTIVE: To estimate the number of undocumented incident traumatic brain injuries (TBIs) among active component US military personnel serving in Iraq and Afghanistan prior to policy changes implemented in late 2006 and 2010 that improved TBI documentation. METHODS: Negative binomial regression was used to model monthly incident TBI counts between December 2010 and June 2012 (N = 19) and then estimate expected monthly counts of incident TBIs during 2 periods: January 2003-October 2006 and November 2006-November 2010. Monthly amputation counts from Department of Defense surveillance data were used as a proxy for changing injury rates. Monthly active component deployment estimates derived from the Congressional Research Service, Brookings Institution, and Defense Manpower Data Center were used to estimate the size of the at-risk population each month. The difference between expected monthly incident TBI counts and reported counts is presented as the estimated number of undocumented incident TBIs. RESULTS: The full model estimates that 21 257 active component military personnel experienced undocumented incident TBIs while deployed in Iraq or Afghanistan between January 2003 and October 2006, more than 4 times the 5272 incident TBIs documented during that period. CONCLUSIONS: A sizeable majority of Iraq and Afghanistan combat veterans who experienced incident TBI while deployed prior to November 2006 are likely to have had their injuries undocumented, creating challenges for clinical care, disability evaluation, and future research.

Mefloquine gap junction blockade and risk of pregnancy loss.

Obstetric use of the antimalarial drug mefloquine has historically been discouraged during the first trimester and immediately before conception owing to concerns of potential fetal harm. With the rise of resistance to the antimalarial drug sulfadoxine-pyrimethamine (SP), mefloquine is now being considered as a replacement for SP for universal antenatal administration to women from malaria-endemic regions. Recent recommendations have also suggested that mefloquine may be used cautiously among pregnant travelers who cannot otherwise avoid visiting these areas. Mefloquine has been demonstrated to cause blockade of gap junction protein alpha 1 (GJA1) gap junction intercellular communication (GJIC), and recent evidence suggests that GJA1 GJIC is critical to successful embryonic implantation and early placental development. During routine use, mefloquine accumulates in organ and peripheral tissue, crosses the blood-placental barrier, and may plausibly accumulate in developing decidua and trophoblast at concentrations sufficient to interfere with GJA1 GJIC and, thus, cause deleterious effects on fetal outcomes. This conclusion is supported by epidemiological evidence that demonstrates use of the drug during early development is associated with an increased risk of miscarriage and stillbirth. Confirmatory studies are pending, but the available experimental and epidemiological evidence support renewed adherence, where feasible, to existing mefloquine package insert guidance that women avoid the drug during the periconceptional period.

Mass administration of the antimalarial drug mefloquine to Guantánamo detainees: a critical analysis.

Recently, evidence has emerged from an unusual form of mass drug administration practised among detainees held at US Naval Station Guantánamo Bay, Cuba ('Guantánamo'), ostensibly as a public health measure. Mefloquine, an antimalarial drug originally developed by the US military, whose use is associated with a range of severe neuropsychiatric adverse effects, was administered at treatment doses to detainees immediately upon their arrival at Guantánamo, prior to laboratory testing for malaria and irrespective of symptoms of disease. In this analysis, the history of mefloquine's development is reviewed and the indications for its administration at treatment doses are discussed. The stated rationale for the use of mefloquine among Guantánamo detainees is then evaluated in the context of accepted forms of population-based malaria control. It is concluded that there was no plausible public health indication for the use of mefloquine at Guantánamo and that based on prevailing standards of care, the clinical indications for its use are decidedly unclear. This analysis suggests the troubling possibility that the use of mefloquine at Guantánamo may have been motivated in part by knowledge of the drug's adverse effects, and points to a critical need for further investigation to resolve unanswered questions regarding the drug's potentially inappropriate use.

Prostate-specific antigen concentration in young men: new estimates and review of the literature.

UNLABELLED: Study Type--Diagnostic (cohort) Level of Evidence 2b. What's known on the subject? and What does the study add? Although non-recommended PSA testing has been reported in men younger than 40 years of age, there are few recognized data on PSA in younger American men, particularly younger African-American men, to provide age- and race-specific references. Using data from an existing large study of young, male members of the US military, aged 28-36 years, the present study provides PSA reference distributions for young Caucasian-American men (median = 0.56, 95th percentile = 1.42, range: <0.01-3.34 ng/mL) and African-American men (median = 0.64, 95th percentile = 1.89, range: 0.12-6.45 ng/mL). Previous estimates from the literature are also summarized. OBJECTIVE: • To provide race-specific prostate-specific antigen (PSA) reference distributions for young men less than 40 years of age who might have undergone non-recommended PSA testing because of their family history of prostate cancer or inadvertently as part of a standard panel of tests. MATERIALS AND METHODS: • We used data from a large existing study of young, male Caucasian- and African-American members of the US military with stored serum in the Department of Defense serum repository. • As part of this previous study, we selected a random sample of 373 Caucasian- and 366 African-American men aged 28-36 years with an archived serum specimen collected for standard military purposes from 2004 to 2006. • We measured serum total PSA concentration in this specimen using the Beckman Coulter Access Hybritech PSA assay. RESULTS: • The PSA level ranged from <0.01 to 3.34 ng/mL among Caucasian-American men, with a median of 0.56 ng/mL and a 95th percentile of 1.42 ng/mL. • The PSA level ranged from 0.12 to 6.45 ng/mL among African-American men, with a median of 0.64 ng/mL and 95th percentile of 1.89 ng/mL. • The PSA level was significantly higher in African- than in Caucasian-American men (P= 0.001). CONCLUSION: • The PSA estimates, together with those summarized from the literature, provide age- and race-specific PSA reference distributions for young men who might have undergone non-recommended PSA testing. • Comparisons by race could also begin to inform the timing of divergence of prostate cancer risk by race.

Enteric disease surveillance under the AFHSC-GEIS: current efforts, landscape analysis and vision forward.

The mission of the Armed Forces Health Surveillance Center, Division of Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) is to support global public health and to counter infectious disease threats to the United States Armed Forces, including newly identified agents or those increasing in incidence. Enteric diseases are a growing threat to U.S. forces, which must be ready to deploy to austere environments where the risk of exposure to enteropathogens may be significant and where routine prevention efforts may be impractical. In this report, the authors review the recent activities of AFHSC-GEIS partner laboratories in regards to enteric disease surveillance, prevention and response. Each partner identified recent accomplishments, including support for regional networks. AFHSC/GEIS partners also completed a Strengths, Weaknesses, Opportunities and Threats (SWOT) survey as part of a landscape analysis of global enteric surveillance efforts. The current strengths of this network include excellent laboratory infrastructure, equipment and personnel that provide the opportunity for high-quality epidemiological studies and test platforms for point-of-care diagnostics. Weaknesses include inconsistent guidance and a splintered reporting system that hampers the comparison of data across regions or longitudinally. The newly chartered Enterics Surveillance Steering Committee (ESSC) is intended to provide clear mission guidance, a structured project review process, and central data management and analysis in support of rationally directed enteric disease surveillance efforts.

Hepatitis E seroprevalence and seroconversion among US military service members deployed to Afghanistan.

BACKGROUND: Hepatitis E virus (HEV) has been recognized as a threat to military forces since its discovery. Although HEV seroprevalence in Afghanistan is not known, HEV infection is thought to be highly endemic in that country. This study determined the incidence of HEV seroconversion among United States (US) service members who were deployed to Afghanistan, as well as the prevalence of antibodies to HEV prior to the deployment. METHODS: A random sample of 1500 subjects was selected from the cohort of service members who were deployed to Afghanistan between 2002 and 2006. Predeployment and postdeployment serum samples from these subjects were tested by enzyme immunoassay for total antibodies to HEV. Results. The seroprevalence of antibodies to HEV in US service members prior to deployment was 1.1%. The seroconversion rate among service members deployed to Afghanistan was 0.13%. CONCLUSIONS: Although subpopulations may be at higher risk for HEV exposure during deployment, the risk among US service members deployed to Afghanistan in this study was low. Previously implemented and current preventive measures in theater appear to have been adequate. With future deployments to new areas or changes in military operations in areas of risk, continued surveillance for HEV infection in the military will be warranted.