Induction of serine protease inhibitor 9 by Mycobacterium tuberculosis inhibits apoptosis and promotes survival of infected macrophages

Our recent microarray analysis of infected human alveolar macrophages (AMs) found serine protease inhibitor 9 (PI-9) to be the most prominently expressed of a cluster of apoptosis-associated genes induced by virulent Mycobacterium tuberculosis. In the current study, we show that induction of PI-9 occurs within hours of infection with M. tuberculosis H37Rv and is maintained through 7 days of infection in both AMs and blood monocytes. Inhibition of PI-9 by small inhibitory RNA decreased M. tuberculosis-induced expression of the antiapoptotic molecule Bcl-2 and resulted in a corresponding increase in production of caspase 3, a terminal effector molecule of apoptosis. Further, PI-9 small inhibitory RNA mediated a significant reduction in the subsequent survival of M. tuberculosis within AMs. Thus PI-9 induction within human mononuclear phagocytes by virulent M. tuberculosis serves to protect these primary targets of infection from elimination by apoptosis and thereby promotes intracellular survival of the organism.     

Acceptability of Peer-Delivered HIV Testing and Counselling Among Men Who Have Sex with Men (MSM) and Transgender Women (TW) in Myanmar

Men who have sex with men (MSM) and transgender women (TW) are a priority population for HIV prevention in Myanmar but report sub-optimal HIV testing frequency. Previous studies have shown that peer involvement in HIV testing can normalize stigmatized sexualities and reduce barriers to testing. We explored the acceptability of peer-delivered HIV testing among 425 undiagnosed MSM and TW in Yangon and Mandalay. An overwhelming majority of participants (86%) reported being ‘comfortable/very comfortable’ with peer-delivered HIV testing. Logistic regression identified reporting sexual identity as Apone [adjusted odds ratio (aOR) 3.8; 95% CI 1.2–11.7], recent HIV testing (aOR 3.1; 95% CI 1.4–6.5), reporting a high likelihood of HIV acquisition (aOR 3.6; 95% CI 1.7–7.6), and reporting ≥ 5 casual partners in the past 3 months (aOR 0.2; 95% CI 0.1–0.6) as associated with peer-delivered HIV testing acceptability. Given ongoing HIV vulnerability among MSM and TW in Myanmar, peer-delivered testing may offer prevention benefits by increasing testing rates and identifying undiagnosed infection earlier.     

Comparative outcomes of thrombocytopenic acute leukemic patients with venous thromboembolism at a Comprehensive Cancer Center

Patients with hematological malignancies often have severe thrombocytopenia, which poses problems when making thrombosis management decisions. A retrospective study was conducted to analyze the clinical outcomes associated with different management options in acute leukemic patients with thrombocytopenia (≤?50?×?10⁹/L) following an acute venous thromboembolic event. A total of 74 patients were divided into three treatment groups: observation only (n?=?30); anticoagulation (n?=?23); or inferior vena cava placement (n?=?21). Multivariate analysis showed that anticoagulant administration was significantly associated with improved overall survival without an increased rate of clinical relevant bleeding events when compared to other thrombosis management modalities. This study notes that dose adjusted-anticoagulant therapy may offer a safe and clinical advantageous strategy for the treatment and secondary prevention of recurrent venous thrombosis in thrombocytopenic patients with hematologic malignancies.     

Visual working memory in decision making by honey bees

The robustness and plasticity of working memory were investigated in honey bees by using a delayed matching-to-sample (DMTS) paradigm. The findings are summarized as follows: first, performance in the DMTS task decreases as the duration between the presentation of the sample stimulus and the presentation of the comparison stimuli is increased. This decrease is well approximated by an exponential decay function. Performance is significantly better than random-choice level even at delays as long as 5 sec and is reduced to random-choice levels at an average delay time of 8.68 +/- 0.06 sec. Second, when the DMTS task involves two samples (one relevant, the other irrelevant), bees can be trained to learn to use the relevant sample to perform the task if (i) the relevant sample is always at a fixed position, or (ii) the relevant sample always has the same place in the sequence of presentation (always first or always second). Bees that have learned to use the relevant sample and to ignore the irrelevant sample can generalize this learning, and apply it to novel sets of sample and comparison stimuli that they have never previously encountered. The findings point to a remarkably robust, and yet plastic, working memory in the honey bee.     

Emergence of a Novel Dengue Virus 3 (DENV-3) Genotype-I Coincident with Increased DENV-3 Cases in Yangon,Myanmar between 2017 and 2019

Dengue fever, caused by the mosquito-borne dengue virus (DENV), has been endemic in Myanmar since 1970 and it has become a significant public health burden. It is crucial that circulating DENV strains are identified and monitored, and that their transmission efficiency and association with disease severity is understood. In this study, we analyzed DENV-1, DENV-2, DENV-3, and DENV-4 serotypes in 1235 serum samples collected in Myanmar between 2017 and 2019. Whole-genome sequencing of DENV-1–4 demonstrated that most DENV-1–4 strains had been circulating in Myanmar for several years. We also identified the emergence of DENV-3 genotype-I in 2017 samples, which persisted through 2018 and 2019. The emergence of the strain coincided with a period of increased DENV-3 cases and marked changes in the serotype dynamics. Nevertheless, we detected no significant differences between serum viral loads, disease severity, and infection status of individuals infected with different DENV serotypes during the 3-year study. Our results not only identify the spread of a new DENV-3 genotype into Yangon, Myanmar, but also support the importance of DENV evolution in changing the epidemic dynamics in endemic regions.     

MEG predicts epileptic zone in lesional extrahippocampal epilepsy: 12 pediatric surgery cases

PURPOSE: To discover whether the spatial distribution of spike sources determined by magnetoencephalography (MEG) provides reliable information for planning surgery and predicting outcomes in pediatric patients with lesional extrahippocampal epilepsy. METHODS: We retrospectively studied 12 children with extrahippocampal epilepsy secondary to cortical dysplasia (CD), tumor, or porencephalic cyst. We compared interictal MEG spike source locations and somatosensory evoked fields derived from equivalent-current dipole modeling with intraoperative or extraoperative electrocorticography (ECoG). RESULTS: MEG spike sources were found in proximity to the lesion in all patients and extended from lesions in five patients with CD. Marginal spike sources were noted in three patients with tumors, one patient with a cyst, and one with CD, and extramarginal sources in three patients with tumors. Three patients with tumors underwent lesionectomy only; two had further cortical excisions. One patient with CD underwent lesionectomy only, three had lesionectomy and cortical excisions, and two had lesionectomy and multiple subpial transection. Asymmetric MEG spike sources correlated with ECoG findings in all patients. Residual epileptiform discharges on postexcisional ECoG corresponded to spike sources in three patients with tumors and one patient with a cyst. Eleven patients have been seizure free for 1-6 years (mean, 4 years). One patient had residual seizures after incomplete excision of right temporal CD. CONCLUSIONS: MEG delineated asymmetric epileptogenicity surrounding lesions and the eloquent cortex. Complete tumor resection produced favorable outcomes despite residual postexcisional ECoG spikes and extramarginal MEG spike sources. CD characterized by clusters of MEG spike sources within and extending from lesions seen on magnetic resonance imaging (MRI) should be removed to prevent seizures.     

Phase I clinical trial of hepatic arterial infusion of paclitaxel in patients with advanced cancer and dominant liver involvement

Purpose  

The survival of patients with liver metastases from solid tumors is poor. We conducted a phase I study of hepatic arterial infusion (HAI) paclitaxel in patients with advanced cancer and predominant liver involvement.