Pulmonary co-morbidity in HIV-infected sputum AFB smear-negative Ugandan adults

Objectives: To determine the extend of comorbidity present in HIV positive and negative patients with respiratory tract infections. Methods: Descriptive cross sectional study. Between October 2002 and December 2003 88 bronchoscopies were analysed at Mulago teaching hospital. Results: 70.5% of the patients were HIV positive with a mean age of 35.1 years. In the HIV positive group, PKS was the most frequent diagnosis made (38.7%), followed by PCP (37.1%) and PTB (14.5%). In the HIV negative group, lung malignancy was the commonest diagnosis found. Ten of the HIV positive patients (16.1%) had two or more pulmonary diseases: two patients had both PCP and PTB, three patients had PKS and PTB, four patients had PKS and PCP, and one patient had PCP, PKS and PTB. When we analysed according to diseases, 30.4% (7/23) of PCP patients had other opportunistic diseases, PKS patients, 30.0% (8/24) and PTB patients, 66.7 % (6/9). Conclusion: The presence of multiple infectious agents may explain why some HIV positive patients with respiratory disease show only temporary clinical improvement. This suggests that one diagnosis may not be enough for HIV patients

A Pilot Study Comparing HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinomas by Whole Exome Sequencing.

Background. Next-generation sequencing of cancers has identified important therapeutic targets and biomarkers. The goal of this pilot study was to compare the genetic changes in a human papillomavirus- (HPV-)positive and an HPV-negative head and neck tumor. Methods. DNA was extracted from the blood and primary tumor of a patient with an HPV-positive tonsillar cancer and those of a patient with an HPV-negative oral tongue tumor. Exome enrichment was performed using the Agilent SureSelect All Exon Kit, followed by sequencing on the ABI SOLiD platform. Results. Exome sequencing revealed slightly more mutations in the HPV-negative tumor (73) in contrast to the HPV-positive tumor (58). Multiple mutations were noted in zinc finger genes (ZNF3, 10, 229, 470, 543, 616, 664, 638, 716, and 799) and mucin genes (MUC4, 6, 12, and 16). Mutations were noted in MUC12 in both tumors. Conclusions. HPV-positive HNSCC is distinct from HPV-negative disease in terms of evidence of viral infection, p16 status, and frequency of mutations. Next-generation sequencing has the potential to identify novel therapeutic targets and biomarkers in HNSCC

Fundamental mode-locking of a composite-cavity electro-optic microchip laser for microwave photonics

International Topical Meeting on Microwave Photonics, MWP 2005, pp. 37-40.Compact solid-state lasers are an attractive potential source for high speed, low noise optical pulses suitable for microwave photonic systems such as optical A/D conversion or digital communications. These small devices can be mode-locked at the fundamental cavity resonance, thereby avoiding the complications arising from the presence of supermodes in harmonically mode-locked lasers. An Nd:YVO4/MgO:LiNbO3 microchip laser was mode-locked at a fundamental frequency of 20 GHz. When locked to a synthesizer, the phase noise was source-limited to -72 dBc/Hz at 1 kHz offset. A coupled optoelectronic oscillator structure was then used to mode-lock the device without a microwave source, yielding a further reduced phase noise of -95 dBc/Hz at 1 kHz offset

A case report and genetic characterization of a massive acinic cell carcinoma of the parotid with delayed distant metastases.

We describe the presentation, management, and clinical outcome of a massive acinic cell carcinoma of the parotid gland. The primary tumor and blood underwent exome sequencing which revealed deletions in CDKN2A as well as PPP1R13B, which induces p53. A damaging nonsynonymous mutation was noted in EP300, a histone acetylase which plays a role in cellular proliferation. This study provides the first insights into the genetic underpinnings of this cancer. Future large-scale efforts will be necessary to define the mutational landscape of salivary gland malignancies to identify therapeutic targets and biomarkers of treatment failure

Pyocyanin-Enhanced Neutrophil Extracellular Trap Formation Requires the NADPH Oxidase

Beyond intracellular killing, a novel neutrophil-based antimicrobial mechanism has been recently discovered: entrapment and killing by neutrophil extracellular traps (NETs). NETs consist of extruded nuclear DNA webs decorated with granule proteins. Although NET formation is an important innate immune mechanism, uncontrolled NET release damages host tissues and has been linked to several diseases including cystic fibrosis (CF). The major CF airway pathogen Pseudomonas aeruginosa establishes chronic infection. Pseudomonas imbedded within biofilms is protected against the immune system, but maintains chronic inflammation that worsens disease symptoms. Aberrant NET release from recruited neutrophils was found in CF, but the underlying mechanisms remain unclear. One of the most important Pseudomonas virulence factors is pyocyanin, a redox-active pigment that has been associated with diminished lung function in CF. Here we show that pyocyanin promotes NET formation in a time- and dose-dependent manner. Most CF Pseudomonas clinical isolates tested produce pyocyanin in vitro. Pyocyanin-derived reactive oxygen species are required for its NET release. Inhibitor experiments demonstrated involvement of Jun N-terminal Kinase (JNK) and phosphatidylinositol 3-Kinase (PI3K) in pyocyanin-induced NET formation. Pyocyanin-induced NETs also require the NADPH oxidase because NET release in chronic granulomatous disease neutrophils was greatly reduced. Comparison of neutrophils from gp91phox- and p47phox-deficient patients revealed that pyocyanin-triggered NET formation is proportional to their residual superoxide production. Our studies identify pyocyanin as the first secreted bacterial toxin that enhances NET formation. The involvement of NADPH oxidase in pyocyanin-induced NET formation represents a novel mechanism of pyocyanin toxicity