Methylene blue@silver nanoprisms conjugates as a strategy against Candida albicans isolated from balanoposthitis using photodynamic inactivation.

Balanoposthitis can affect men in immunocompromised situations, such as HIV infection and diabetes. The main associated microorganism is Candida albicans, which can cause local lesions, such as the development of skin cracks associated with itching. As an alternative to conventional treatment, there is a growing interest in the photodynamic inactivation (PDI). It has been shown that the association of photosensitizers with metallic nanoparticles may improve the effectiveness of PDI via plasmonic effect. We have recently shown that the association of methylene blue (MB), a very known photosensitizer, with silver prismatic nanoplatelets (AgNPrs) improved PDI of a resistant strain of Staphylococcus aureus. To further investigate the experimental conditions involved in PDI improvement, in the present study, we studied the effect of MB concentration associated with AgNPrs exploring spectral analysis, zeta potential measurements, and biological assays, testing the conjugated system against C. albicans isolated from a resistant strain of balanoposthitis. The AgNPrs were synthesized through silver anisotropic seed growth induced by the anionic stabilizing agent poly(sodium 4-styrenesulfonate) and showed a plasmon band fully overlapping the MB absorption band. MB and AgNPrs were conjugated through electrostatic association and three different MB concentrations were tested in the nanosystems. Inactivation using red LED light (660 nm) showed a dose dependency in respect to the MB concentration in the conjugates. Using the highest MB concentration (100 µmol⋅L-1) with AgNPr, it was possible to completely inactivate the microorganisms upon a 2 min irradiation exposure. Analyzing optical changes in the conjugates we suggest that these results indicate that AgNPrs are enhancers of MB photodynamic action probably by a combined mechanism of plasmonic effect and reduction of MB dimerization. Therefore, MBAgNPrs can be considered a suitable choice to be applied in PDI of resistant microorganisms.

Low Testosterone in Men with Cardiovascular Disease or Risk Factors: To Treat or Not To Treat?

OPINION STATEMENT: Current evidence supports the use of testosterone replacement in men with the clinical-biochemical syndrome of hypogonadism, defined as low testosterone serum levels and symptoms such as fatigue, exercise intolerance, erectile dysfunction, low libido, or depression. Although the evidence consistently shows that hypogonadism is associated with elevated cardiovascular risk, evidence is mixed regarding whether testosterone (T) replacement provides cardiovascular (CV) benefit or harm. For a man with symptomatic hypogonadism in the setting of CV disease, clinical heart failure, and/or traditional CV risk factors (hypertension, diabetes, and hyperlipidemia), a balanced approach would be to counsel him that overall, the evidence should not dissuade him from utilizing T replacement for non-cardiac symptom relief but that more data are needed before a definitive recommendation can be made about T replacement for CV benefit. The preponderance of available evidence, reviewed in this article, suggests that T replacement, at appropriate doses and with monitored response, is likely to be safe for men with CV disease or CV risk factors and may even reduce major adverse cardiovascular events (MACE). The 2015 American Association of Clinical Endocrinologists and American College of Endocrinology position statement supports this stance and calls for improved prospective data. There is a clear need for a large, prospective randomized trial evaluating the impact of T replacement on MACE, for men both with and without CV disease or CV risk factors. Clinicians should be aware that all men who elect to take T replacement therapy require regular follow-up with the prescribing physician to include both clinical assessment and surveillance laboratory assessment of total T level, complete blood count, and prostate specific antigen.

America vs Europe and the 2014 Non-ST Elevation Acute Coronary Syndrome Guidelines.

In August of 2014, the American Heart Association and American College of Cardiology (AHA/ACC) published a new guideline for the management of patients with non-ST-elevation acute coronary syndromes. With similar timing, the European Association for Cardio-Thoracic Surgery (EACTS) released new 2014 guidelines on myocardial revascularization, including a brief update on the 2011 European Society of Cardiology guidelines on the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. We briefly summarize key components of all three of these guideline publications, highlighting differences and concluding that similarities far outweigh differences in the American vs European approach to a patient with non-ST-elevation acute coronary syndrome.

Left ventricular myocardial injury and syncope due to pulmonary embolism in a soldier: normal coronaries and novel pathologic electrocardiogram signs.

OBJECTIVE: We present a soldier with a pulmonary embolism presenting with syncope during an ischemic stress test, subsequently found to have normal coronary arteries (CA). CASE: A 49-year-old soldier had 3 months history of exertional chest pain, shortness of breath, syncope, and malaise. He passed out during a stress echocardiogram and had a positive troponin level. A subsequent cardiac catheterization revealed normal CA but with mild hypokinesis of the distal anterior wall with a left ventricular ejection fraction of 44%. A subsequent nuclear ventilation-perfusion scan was consistent with bilateral pulmonary embolism. RESULTS: A Doppler ultrasound revealed thrombosis in the distal superficial femoral vein of the left leg. Hypercoagulable state markers were normal. CONCLUSION: This case demonstrates that a pulmonary embolism could express itself as an ST depression myocardial ischemic event perhaps by affecting the coronary flow to the left anterior descending CA.

PKC-epsilon-dependent cytosol-to-membrane translocation of pendrin in rat thyroid PC Cl3 cells.

We studied the expression and the hormonal regulation of the PDS gene product, pendrin, which is, in thyrocytes, responsible for the iodide transport out of the cell. We show that PC Cl3 cells, a fully differentiated thyroid cell line, grown without TSH and insulin, express very low level of PDS mRNA; such expression is greatly increased after stimulation with insulin or TSH. (125)I pre-loaded cells showed an (125)I efflux accelerated in chloride-containing buffer with respect to chloride-free buffer, suggesting that this efflux is chloride dependent. By immunoblotting, pendrin was found in agonists-stimulated cells, whereas it was barely detectable in un-stimulated cells. An increase in both PDS mRNA and protein was also obtained using phorbol ester PMA, or using 8-Br-cAMP and forskolin. Stimulation with insulin (1 microg/ml; 0-40 min) provoked the cytosol-to-membrane translocation of pendrin and a decrease of intracellular I(-) content in (125)I pre-loaded cells. Insulin- or PMA-treated cells also showed a cytosol-to-membrane translocation of PKC-delta and -epsilon. Inhibition of both PKC-delta and -epsilon activities by GF109203X blocked pendrin translocation, whilst the inhibition of PKA did not. The selective inhibition of PKC-delta by rottlerin did not affect the insulin-provoked translocation of pendrin whilst it was inhibited by a PKC-epsilon translocation inhibitor peptide and also by PKC-epsilon downregulation using the small interfering RNA, thus indicating that such translocation was due to PKC-epsilon activity. In conclusion, our study demonstrates that, in PC Cl3 cells, pendrin expression and localisation are regulated by insulin and influenced by a PKC-epsilon-dependent intracellular pathway.

Venous thromboembolism among United States soldiers deployed to Southwest Asia.

INTRODUCTION: Military operations may represent a high-risk environment for venous thromboembolism (VTE). We sought to identify and describe cases of venous thromboembolism among US military personnel serving in Southwest Asia, and estimate relative disease rates compared to non-deployed personnel. MATERIALS AND METHODS: Retrospective review of imaging archives, hospital discharge codes, case logs and autopsy records for the diagnosis of deep vein thrombosis or pulmonary embolism occurring from 1 March 2003 through 29 February 2004 among U.S. military personnel deployed to Southwest Asia. Rates of disease in deployed and non-deployed active-duty soldiers were estimated using personnel data and deployment experience obtained from automated rosters. RESULTS: Forty cases of venous thromboembolism were identified. The case-fatality rate was 16% (3/19) among those with pulmonary embolism. Antecedent trauma followed by prolonged air evacuation was present in 55% (22/40). Compared to trauma-associated cases, non-trauma cases were more commonly over 40 years old (44% vs. 5%; p<0.05), assigned to a transportation or quartermaster company (56% vs. 14%; p<0.05), or had a history of remote venous thromboembolism (31% vs. 0%; p<0.05). The overall incidence among deployed active-duty soldiers was 22.1/100,000 person-years. Compared to non-deployed active-duty soldiers, the age-adjusted incidence rate ratio was 1.06 (CI(0.95) 0.68-1.67). CONCLUSIONS: VTE rates among deployed soldiers are relatively low compared to the general population, and are comparable to non-deployed soldiers. Fatalities from PE are not uncommon, and vigilance among clinicians remains warranted. Trauma followed by prolonged air evacuation or ground transport during military operations may represent unique interactive risk factors for venous thromboembolism.

Incidence and follow-up of inflammatory cardiac complications after smallpox vaccination.

OBJECTIVES: The purpose of this study was to assess the follow-up of patients with vaccinia-associated myocarditis. BACKGROUND: With the threat of biological warfare, the U.S. Department of Defense resumed a program for widespread smallpox vaccinations on December 13, 2002. One-year afterwards, there has been a significant increase in the occurrence of myocarditis and pericarditis among those vaccinated. METHODS: Cases were identified through sentinel reporting to military headquarters, systematic surveillance, and spontaneous reports. RESULTS: A total of 540,824 military personnel were vaccinated with a New York City Board of Health strain of vaccinia from December 2002 through December 2003. Of these, 67 developed myopericarditis at 10.4 +/- 3.6 days after vaccination. The ST-segment elevation was noted in 57%, mean troponin on admission was 11.3+/- 22.7 ng/dl, and peak cardiac enzymes were noted within 8 h of presentation. On follow-up of 64 patients (96%) at a mean of 32 +/- 16 weeks, all patients had objective normalization of echocardiography, electrocardiography, laboratory testing, graded exercise testing, and functional status; 8 (13%) reported atypical, non-limiting persistent chest discomfort. CONCLUSIONS: Post-vaccinial myopericarditis should be considered in patients with chest pain within 30 days after smallpox vaccination. Normalization of echocardiography, electrocardiography, and treadmill testing is expected, and nearly all patients have resolution of chest pain on follow-up.

Smallpox vaccination and myopericarditis: a clinical review.

Smallpox is a devastating viral illness that was eradicated after an aggressive, widespread vaccination campaign. Routine U.S. childhood vaccinations ended in 1972, and routine military vaccinations ended in 1990. Recently, the threat of bioterrorist use of smallpox has revived the need for vaccination. Over 450,000 U.S. military personnel received the vaccination between December 2002 and June 2003, with rates of non-cardiac complications at or below historical levels. The rate of cardiac complications, however, has been higher than expected, with two confirmed cases and over 50 probable cases of myopericarditis after vaccination reported to the Department of Defense Smallpox Vaccination Program. The practicing physician should use the history and physical, electrocardiogram, and cardiac biomarkers in the initial evaluation of a post-vaccination patient with chest pain. Echocardiogram, cardiac catheterization, magnetic resonance imaging, nuclear imaging, and cardiac biopsy may be of use in further workup. Treatment is with non-steroidal anti-inflammatory agents, four to six weeks of limited exertion, and conventional heart failure treatment as necessary. Immune suppressant therapy with steroids may be uniquely beneficial in myopericarditis related to smallpox vaccination, compared with other types of myopericarditis. If a widespread vaccination program is undertaken in the future, many more cases of post-vaccinial myopericarditis could be seen. Practicing physicians should be aware that smallpox vaccine-associated myopericarditis is a real entity, and symptoms after vaccination should be appropriately evaluated, treated if necessary, and reported to the Vaccine Adverse Events Reporting System.

A 55-year-old mechanically ventilated male requiring aeromedical evacuation.

OBJECTIVE: To present a case that illustrates the problems unique to transporting a mechanically ventilated patient by air. A 55-year-old mechanically ventilated male with Guillain-Barre Syndrome, a condition with respiratory effects often similar to those of traumatic brain injury, required air transport from Walter Reed Army Medical Center in Washington, DC, to a hospital in Nevada. A medical team, including one physician, one nurse, and one respiratory therapist, accompanied the patient. This team was not trained in air travel and its unique risks. To complete the mission they had to rapidly familiarize themselves with the specific risks of air travel and the precautions that should be taken. This case is presented to illustrate these risks and what can be done during flight to minimize them.

Neurotrophins prevent HIV Tat-induced neuronal apoptosis via a nuclear factor-kappaB (NF-kappaB)-dependent mechanism.

HIV-1 associated dementia is thought to be caused by neuronal damage and death in response to the production of soluble neurotoxic factors by virally infected mononuclear phagocytes. These neurotoxins include HIV-1 Tat. The ability of neurotrophins to promote cell survival prompted us to examine whether neurotrophins might also be capable of opposing the pro-apoptotic effects of Tat. Here, we show that Tat-induced neuronal apoptosis in primary cultures of rat cerebellar granule cells and in neuronally differentiated human SK-N-MC cells is profoundly inhibited by brain-derived neurotrophic factor, nerve growth factor and activity-dependent neurotrophic factor nonamer peptide. These neurotrophins activated the transcription factor NF-kappaB, and inhibition of NF-kappaB activation using a super-repressor IkappaB-alpha mutant was found to block the survival-promoting activity of the neurotrophins. Reporter gene assays and immunoblot experiments revealed that the neurotrophins also up-regulated the expression of Bcl-2, at both the transcriptional and protein levels. Overexpression of the super-repressor IkappaB-alpha mutant prevented this induction of Bcl-2 expression. Moreover, overexpression of either Bcl-2, alone, or the RelA subunit of NF-kappaB, alone, protected neurons from Tat-induced apoptosis. These findings suggest that the activation of NF-kappaB by neurotrophic factors may promote survival of neurons exposed to Tat, via regulation of anti-apoptotic genes including Bcl-2.