In 2014, WHO reported approximately 9.6 million new cases of tuberculosis (TB) in the world, more than half of which are contributed by developing countries in Asia and Africa. Lack of modern diagnostic tools, underreporting of the new cases and underutilization of directly observed therapy (DOT) remain a concern in developing countries. Transient resurgence of TB during the HIV epidemic has subsided and the annual decline has resumed in developed countries including the USA. In 2014 though, the rate of decline has slowed down resulting in leveling of TB incidence in the USA. In developed countries like the USA, the incidence of TB remains high in those with certain risk factors for TB. This group includes immunocompromised patients, particularly those with positive HIV infection. Others at high risk include those with diabetes, cancer, those taking immunosuppressive drugs, and those with other medical conditions that reduce host immunity. If we look at age and ethnicity, elderly patients are at higher risk of developing TB. African-American, foreign-born, and homeless populations are also at higher risk of developing tuberculosis. Virulence of the mycobacteria, and immunological and genetically mediated factors are also mentioned, but these topics are not the primary goal of this article. This review, thus discusses the epidemiology, host factors, and those at high risk for developing active TB. A brief review of the current trends in drug resistance of mycobacteria is also presented.

Clopidogrel is an irreversible antiplatelet agent belonging to the thienopyridine group that acts to antagonize the adenosine diphosphate P2Y12 receptor on platelets. It thus inhibits the activation of platelet glycoprotein GPIIb/IIIa complex, which is essential for fibrinogen—platelet complex formation. Clopidogrel has widely replaced ticlopidine because of a much better clinical safety profile. Clopidogrel is a prodrug that requires hepatic activation to exert its antiplatelet effect. Hepatotoxicity with use of clopidogrel is a rare but clinically significant phenomenon. We report a case of clopidogrel-induced hepatotoxicity in an elderly white woman.

No description available.

Systemic lupus erythematosus (SLE) is an autoimmune disease affecting multiple organ systems. Although myocardial involvement and overt myocarditis is rare, life-threatening myocarditis associated with SLE can happen. We report a case of myocarditis associated with SLE with subsequent improvement of cardiac function after immunosuppressive therapy.

T cells play a crucial role in viral clearance or persistence; however, the precise mechanisms that control their responses during viral infection remain incompletely understood. MicroRNA (miR) has been implicated as a key regulator controlling diverse biological processes through posttranscriptional repression. Here, we demonstrate that hepatitis C virus (HCV)-mediated decline of miR-181a expression impairs CD4+ T-cell responses through overexpression of dual specific phosphatase 6 (DUSP6). Specifically, a significant decline of miR-181a expression along with overexpression of DUSP6 was observed in CD4+ T cells from chronically HCV-infected individuals compared to healthy subjects, and the levels of miR-181a loss were found to be negatively associated with the levels of DUSP6 overexpression in these cells. Importantly, reconstitution of miR-181a or blockade of DUSP6 expression in CD4+ T cells led to improved T-cell responses including enhanced CD25 and CD69 expression, increased interleukin-2 expression, and improved proliferation of CD4+ T cells derived from chronically HCV-infected individuals. Conclusion: Since a decline of miR-181a concomitant with DUSP6 overexpression is the signature marker for age-associated T-cell senescence, these findings provide novel mechanistic insights into HCV-mediated premature T-cell aging through miR-181a-regulated DUSP6 signaling and reveal new targets for therapeutic rejuvenation of impaired T-cell responses during chronic viral infection. (Hepatology 2015;61:1163-1173).

Hypothyroidism is easily treated by levothyroxine therapy which has an 80 percent absorption rate, mostly in the jejunum. The replacement dose of daily levothyroxine is usually calculated at 1.6 mcg/kg body weight per day. We report a 77-year-old man who required supraphysiologic thyroxine replacement (>2.7 mcg/ kg/day) to treat his hypothyroidism. The patient was referred for persistent thyroid stimulating hormone (TSH) elevation (40 mcIU/ml) while on 175 mcg of levothyroxine. Patient was compliant with medication. Medical history included diabetes mellitus type 2, cerebrovascular accident, depression, hypertension, hyperlipidemia, atherosclerotic cardiovascular disease, vitamin B12 deficiency, Addison’s disease, as well as a colostomy secondary to diverticulitis. He was taking aspirin, carvedilol, cholecalciferol, finasteride, fluoxetine, furosemide, ketoconazole, levothyroxine, prednisone, and albuterol/ipratropium inhaler. His height was 180.3 cm; weight, 107 kg. Thyroid was impalpable, and he was clinically euthyroid. Despite discontinuation of iron and statin which are known to interfere with thyroxine absorption and crushing of thyroxine tablets to enhance absorption, his TSH remained elevated. Celiac disease and Helicobacter pylori infection were ruled out with serological testing. There was no proteinuria and anti-parietal cell antibody was positive. Gastroparesis was confirmed by gastric emptying study. He continued to require increasing doses of thyroxine with increment to 300 mcg daily. To our knowledge, this is the first documented association between gastroparesis and thyroxine malabsorption. We recommend that gastroparesis be considered in any patient with persistent TSH elevation despite usual thyroxine doses.

Opioids have been widely applied in clinics as one of the most potent pain relievers for centuries, but their abuse has deleterious physiological effects including immunosuppression. However, the mechanisms are unclear. TLRs and acetylcholine are widely expressed in the immune and nervous systems, and play critical roles in immune responses. In this article, we show that morphine suppresses the innate immunity in microglia and bone marrow-derived macrophages through differential regulation of TLRs and acetylcholinesterase. Either morphine or inhibition of acetylcholine significantly promotes upregulation of microRNA-124 (miR-124) in microglia, bone marrow-derived macrophages, and the mouse brain, where miR-124 mediates morphine inhibition of the innate immunity by directly targeting a subunit of NF-κB p65 and TNFR-associated factor 6 (TRAF6). Furthermore, transcription factors AP-1 and CREB inhibited miR-124, whereas p65 bound directly to promoters of miR-124, thereby enhancing miR-124 transcription. Moreover, acute morphine treatment transiently upregulated the expression of p65 and phospho-p65 in both nucleus and cytoplasm priming the expression of miR-124, whereas long exposure of morphine maintained miR-124 expression, which inhibited p65- and TRAF6-dependent TLR signaling. These data suggest that modulation of miRs is capable of preventing opioid-induced damage to microglia.

No description available.

No description available.

Plant-insect interactions are vital for structuring terrestrial ecosystems. It is still unclear how climate change in geological time might have shaped plant-insect interactions leading to modern ecosystems. We investigated the effect of Quaternary climate change on plant-insect interactions by observing insect herbivory on leaves of an evergreen sclerophyllous oak lineage (Quercus section Heterobalanus, HET) from a late Pliocene flora and eight living forests in southwestern China. Among the modern HET populations investigated, the damage diversity tends to be higher in warmer and wetter climates. Even though the climate of the fossil flora was warmer and wetter than modern sample sites, the damage diversity is lower in the fossil flora than in modern HET populations. Eleven out of 18 damage types in modern HET populations are observed in the fossil flora. All damage types in the fossil flora, except for one distinctive gall type, are found in modern HET populations. These results indicate that Quaternary climate change did not cause extensive extinction of insect herbivores in HET forests. The accumulation of a more diverse herbivore fauna over time supports the view of plant species as evolutionary islands' for colonization and turnover of insect species.