Catalytic Cascade Reactions Inspired by Polyketide Biosynthesis.

Aldol reactions belong to the most important methods for carbon-carbon bond formation and are also involved in one of the most astonishing biosynthetic processes: the biosynthesis of polyketides governed by an extraordinarily sophisticated enzymatic machinery. In contrast to the typical linear or convergent strategies followed in chemical synthesis, this late-stage catalysis concept allows Nature to assemble intermediates that are diversified into a broad range of scaffolds, which assume various crucial biological functions. To transfer this concept to small-molecule catalysis to access products beyond the natural systems, a stepwise approach to differentiate increasingly complex substrates was followed by investigating arene-forming polyketide cyclizations.

Catalytic Arene-forming Aldol Condensation: Stereoselective Synthesis of Rotationally Restricted Aromatic Compounds.

By taking inspiration from the fascinating biosynthetic machinery that creates aromatic polyketides, our group investigates analogous reactions catalyzed by small molecules. We are particularly captivated by the prospects of intramolecular aldol condensation reactions to generate different rotationally restricted aromatic compounds. In a first project of our independent research group, a highly stereoselective amine catalyzed synthesis of axially chiral biaryls, tertiary aromatic amides and oligo-1,2-naphthylenes has been developed.

Gene expression profiling reveals a close relationship between follicular lymphoma grade 3A and 3B, but distinct profiles of follicular lymphoma grade 1 and 2.

A linear progression model of follicular lymphomas (FL) FL1, FL2 and FL3A has been favored, since FL3A often co-exist with an FL1/2 component. FL3B, in contrast, is thought to be more closely related to diffuse large B-cell lymphoma (DLBCL), and both are often simultaneously present in one tumor (DLBCL/FL3B). To obtain more detailed insights into follicular lymphoma progression, a comprehensive analysis of a well-defined set of FL1/2 (n=22), FL3A (n=16), FL3B (n=6), DLBCL/FL3B (n=9), and germinal center B-cell-type diffuse large B-cell lymphoma (n=45) was undertaken using gene expression profiling, immunohistochemical stainings and genetic analyses by fluorescence hybridization.

Stereoselective Arene-Forming Aldol Condensation: Catalyst-Controlled Synthesis of Axially Chiral Compounds.

The fundamental role that aldol chemistry adopts in various disciplines, such as stereoselective catalysis or the biosynthesis of aromatic polyketides, illustrates its exceptional versatility. On the one hand, numerous aldol addition reactions reliably transfer the stereochemical information from catalysts into various valuable products. On the other hand, countless aromatic polyketide natural products are produced by an ingenious biosynthetic machinery based on arene-forming aldol condensations.

Low-cost thermotherapy for cutaneous leishmaniasis in Sindh, Pakistan.

Objective: To study the efficacy of a low-cost heating pack device used for thermotherapy in the treatment of cutaneous leishmaniasis.

Methods: The study was conducted at the Department of Dermatology, Civil Hospital Sukkur, Pakistan, from April 20, 2012, to January 3, 2013. Thermotherapy with Hand-Held Exothermic Crystallisation Therapy for cutaneous leishmaniasis was performed on each lesion of the participating subjects at an average initial temperature of 51.

Novel low-cost thermotherapy for cutaneous leishmaniasis in Peru.

Thermotherapy is an accepted alternative therapy for new-world cutaneous leishmaniasis, but current heat-delivery modalities are too costly to be made widely available to endemic populations. We adapted a low-cost heat pack named the HECT-CL device that delivers safe, reliable, and renewable conduction heat. 25 patients with cutaneous leishmaniasis completed treatment with the device at an initial temperature of 52°C ± 2°C for 3 minutes to each lesion, repeated daily for 7 days, and were followed up for 6 months by direct observation.

Molecular detection and diversity of novel diterpenoid dioxygenase DitA1 genes from proteobacterial strains and soil samples.

Resin acids are tricyclic diterpenoids naturally synthesized by trees that are released from wood during pulping processes. Using a newly designed primer set, genes similar to that encoding the DitA1 catalytic alpha-subunit of the diterpenoid dioxygenase, a key enzyme in abietane resin acid degradation by Pseudomonas abietaniphila BKME-9, could be amplified from different Pseudomonas strains, whereas ditA1 gene sequence types representing distinct branches in the evolutionary tree were amplified from Burkholderia and Cupriavidus isolates. All isolates harbouring a ditA1-homologue were capable of growth on dehydroabietic acid as the sole source of carbon and energy and reverse transcription polymerase chain reaction analysis in three strains confirmed that ditA1 was expressed constitutively or in response to DhA, demonstrating its involvement in DhA-degradation.

Mycobacterium kansasii in HIV patients: clarithromycin and antiretroviral effects.

Setting: Charity Hospital New Orleans, Louisiana, USA.

Objective: To define the differences between the pre-HAART (highly active anti-retroviral treatment) and HAART eras in patients co-infected with Mycobacterium kansasii and the human immunodeficiency virus (HIV).

Design: A retrospective chart review revealed 82 patients with HIV and M.

Delays in diagnosis and therapy of gastric cancer and esophageal adenocarcinoma.

Background And Study Aims: In the past, there were long delays in the diagnosis of patients with cancer of the stomach or esophagus. The objective of this study was to describe current delays in the diagnosis and treatment of gastric and esophageal adenocarcinoma and to compare the findings with those from an historical control population treated at the same institutions 10 years earlier.

Patients And Methods: Patients with biopsy-proven gastric cancer or esophageal adenocarcinoma who were treated at two academic medical centers in Germany between April and October 2003 were consecutively screened for eligibility to take part in the study.

Zinc and iron supplementation and malaria, diarrhea, and respiratory infections in children in the Peruvian Amazon.

Iron and zinc deficiencies are common in developing countries and supplementation is one way of reversing these deficiencies. The objective of this randomized, placebo-controlled clinical trial was to identify the effect of daily supplementation with iron, zinc, and iron plus zinc on the morbidity experience of 855 children 0.5-15 years of age in Peru.

Assessment of toluene/biphenyl dioxygenase gene diversity in benzene-polluted soils: links between benzene biodegradation and genes similar to those encoding isopropylbenzene dioxygenases.

The PCR-single-strand conformation polymorphism (SSCP) technique was used to assess the diversity and distribution of Rieske nonheme iron oxygenases of the toluene/biphenyl subfamily in soil DNA and bacterial isolates recovered from sites contaminated with benzene, toluene, ethylbenzene, and xylenes (BTEX). The central cores of genes encoding the catalytic alpha subunits were targeted, since they are responsible for the substrate specificities of these enzymes. SSCP functional genotype fingerprinting revealed a substantial diversity of oxygenase genes in three differently BTEX-contaminated soil samples, and sequence analysis indicated that in both the soil DNA and the bacterial isolates, genes for oxygenases related to the isopropylbenzene (cumene) dioxygenase branch of the toluene/biphenyl oxygenase subfamily were predominant among the detectable genotypes.

Performance of a bioreactor with submerged membranes for aerobic treatment of municipal waste water.

Aerobic treatment of municipal waste water in a membrane bioreactor was studied for 535 d. Apart from sampling, sludge was retained completely by a submerged hollow fibre membrane with a pore-size of 0.2 microm.

Microbiological aspects of a bioreactor with submerged membranes for aerobic treatment of municipal wastewater.

An aerobic membrane bioreactor treating municipal wastewater at complete biomass retention was studied in respect of microbiological parameters over a period of 380 days. The results were compared to those obtained from a conventional activated sludge wastewater treatment plant (WWTP) treating the same wastewater. Microscopically, significant changes in the structure of the flocs and of the ratio between free suspended and aggregated cells could be observed.

The road to indigenous extinction: case study of resource exportation, disease importation, and human rights violations against the Urarina in the Peruvian Amazon.

Isolated Amazonian peoples such as the Urarina in Peru remain at risk of cultural and biological extinction from industrial exploitation and imported diseases. In the last seven years, many Urarina have died in epidemics of measles, cholera, pertussis, and malaria. The Peruvian government has encouraged oil exploration and logging in the Amazon without regard to Urarina rights, and the international treaty promoting indigenous rights that Peru ratified is not enforced.

Malaria reemergence in the Peruvian Amazon region.

Epidemic malaria has rapidly emerged in Loreto Department, in the Peruvian Amazon region. Peru reports the second highest number of malaria cases in South America (after Brazil), most from Loreto. From 1992 to 1997, malaria increased 50-fold in Loreto but only fourfold in Peru.

Rapid, low-technology MIC determination with clinical Mycobacterium tuberculosis isolates by using the microplate Alamar Blue assay.

A colorimetric, microplate-based Alamar Blue assay (MABA) method was used to determine the MICs of isoniazid (INH), rifampin, streptomycin (SM), and ethambutol (EMB) for 34 Peruvian Mycobacterium tuberculosis isolates (including both pansensitive and multidrug-resistant strains) and the H37Rv strain by using bacterial suspensions prepared directly from solid media. Results for all isolates were available within 8 days. Discordant results were observed on initial tests for 3 of 16 INH-susceptible isolates, 5 of 31 EMB-susceptible isolates, and 2 of 4 SM-resistant isolates (by the BACTEC 460 system).

The medicalization of race: scientific legitimization of a flawed social construct.

The term "race" has many definitions, ranging from a family unit to a species, but in common and medical usage, defining "race" has meant separating Homo sapiens into three to six groups. This division of Homo sapiens into race taxons started in the 18th century, when the sciences of genetics and evolutionary biology were not yet invented. These disciplines have since shown that human race taxonomy has no scientific basis.

Aspergillus flavus mycetoma and epidural abscess successfully treated with itraconazole.

Aspergillus spp. rarely cause mycetomata. We report a patient with diabetes and nephrotic syndrome with Aspergillus flavus mycetoma of the back, with the development of an epidural abscess, diskitis and vertebral osteomyelitis.

Clinical manifestations and implications of coinfection with Mycobacterium kansasii and human immunodeficiency virus type 1.

We conducted a retrospective study to further elucidate the clinical presentations and prognosis of disease due to Mycobacterium kansasii in patients infected with human immunodeficiency virus (HIV). Forty-nine HIV-infected patients first had M. kansasii isolated at a mean CD4 cell count of 62/mm3 and at a mean interval of 17 months after the diagnosis of AIDS.

Blastomycosis and human immunodeficiency virus: three new cases and review.

Reports of blastomycosis in individuals infected with the human immunodeficiency virus (HIV) are increasing. We report on 3 patients co-infected with blastomycosis and HIV (to add to the previously reported 21), and review important clinical aspects and outcomes in all cases. The percentage of patients co-infected with blastomycosis and HIV who had disseminated blastomycosis (63%) was similar to the blastomycosis patients in the general population (67%); however, as a group the patients with HIV were severely immunosuppressed and fared poorly.