Assessing quality of life for multidrug-resistant and extensively drug-resistant tuberculosis patients.

OBJECTIVE: One can hypothesize that Mycobacterium genus originated more than 150 million years ago and has evolved to become one of the leading lethal infectious diseases. Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) patients are directly affected by the disease and other subjective issues, such as related diseases, medical costs and social issues, which all have negative impacts on patient quality of life (QOL). Our purpose is to define the status of health-related QOL for international MDR-TB and XDR-TB patients. METHODS: Systematic review is a good method for searching and selecting related researches and articles. As such, we have searched for and cited related articles on reputable databases, such as PubMed, Cochrance, and Google Scholar. A data overview was performed to draw conclusions and results on the QOL of MDR-TB and XDR-TB patients. RESULTS: A total of 18 articles were included, using instruments from the World Health Organization, Euroqol, Short Form, AQ and the Seattle Obstructive Lung Disease Questionnaire. The QOL of MDR-TB and XDR-TB patients was found to be compromised due to the strong resistance of Mycobacterium tuberculosis, economic pressure and community alienation. CONCLUSIONS: A number of QOL and health-related QOL studies on MDR-TB and XDR-TB patients are limited, especially with XDR-TB patients. Significant numbers of MDR-TB and XDR-TB patients still have sequelae after completing treatment, reducing the health-related QOL among these patients.

Copper-Catalyzed Aminoboration from Hydrazones To Generate Borylated Pyrazoles.

Herein we report an aminoboration reaction that employs inexpensive, Earth-abundant, and commercially available Cu(OTf)2 as an effective catalyst in the direct addition of B-N σ bonds to C-C π bonds, generating borylated pyrazoles, which are useful building blocks for drug discovery. By nature of the mechanism, the reaction produces exclusively one regioisomer and tolerates groups incompatible with alternative lithiation/borylation and iridium-catalyzed C-H activation/borylation methods. The reaction can be scaled up, and the resulting isolable pyrazole pinacol boronates can be further functionalized through palladium-catalyzed Suzuki cross-coupling reactions.

An Oxyboration Route to a Single Regioisomer of Borylated Dihydrofurans and Isochromenes.

An oxyboration reaction that employs B-O σ bonds as addition partners to C-C π bonds to form borylated dihydrofurans and isochromenes has been developed. By nature of the mechanism, the reaction produces exclusively one borylated regioisomer, in contrast to and/or complementary to alternative routes that produce these borylated heterocycles via C-H activation. Access to the borylative heterocyclization route is demonstrated from alcohols directly or from a hydroboration-oxyboration sequence starting from the corresponding ketone, forming the heterocyclic core and installing the boron in one synthetic step. Catechol boronates were directly used as coupling partners in the in situ Suzuki cross-coupling reactions without transesterification to pinacol boronates.

Boron-Heteroatom Addition Reactions via Borylative Heterocyclization: Oxyboration, Aminoboration, and Thioboration.

Organoboron compounds and heterocycles are powerful building blocks and precursors for organic synthesis, including for drug discovery and agrochemical and material synthesis. The common strategy for the synthesis of borylated heterocycles involves two separate synthetic steps: first, synthesis of the heterocyclic core, and second, borylation of the core through established methods such as transition-metal-catalyzed C-H or C-X activation/borylation or lithiation/borylation. In this Account, we describe our laboratory's development of borylative heterocyclization reactions that access the heterocyclic core and install boron in one synthetic step. These methods provide complementary bond disconnections, regiochemistry, and functional-group compatibility to current methods. We describe our methods with two categories: a direct borylation method that refers to addition reactions starting from a preformed B-element σ bond, which is essential in the mechanistic route to product formation, and a formal borylation method that refers to addition reactions that do not require formation of a B-element bond but instead proceed through carbon-carbon π-bond activation by an electrophilic boron source followed by dealkylation or deacylation. Through electrophilic activation of the alkyne rather than activation of the B-element bond, formal borylation provides a complementary strategy toward neutral organoboron reagents. We first studied direct oxyboration toward the formation of borylated benzofurans, where a preformed boron-oxygen σ bond is added across an alkyne activated by a carbophilic gold catalyst. We describe detailed mechanistic and kinetic studies of this class of reactions. Application of the knowledge gained from these studies aided in the future development of additional direct borylation reactions involving boron-nitrogen and boron-oxygen σ bonds to form borylared indoles and isoxazoles, respectively. Formal addition of boron/oxygen equivalents to effect oxyboration to form borylated lactones from o-alkynyl esters is then described. This class of reactions takes advantage of bifunctional ClBcat as a carbophilic carbon-carbon π-bond activator and eventual dealkylating agent. We describe our motivation in developing this new class of catalyst-free borylation reactions and subsequently applying the formal borylation strategy to the thioboration of o-alkynylthioanisole substrates to form borylated benzothiophenes. We then proceed to describe our investigations into the details of the mechanism of the formal thioboration reaction. These collaborative mechanistic studies included experimental and computational findings that elucidated the rate-determining step and intermediates of the reaction. These studies further compared different boron sources as electrophiles, including those used in other known reactions, providing fundamental knowledge about the capabilities of commercially available boron reagents toward borylative heterocyclization. Our findings provide guiding principles for reaction design and information leading toward the design of a diverse set of boron-heteroatom addition reactions and their formal equivalents that proceed through borylative heterocyclization.

Oxyboration with and without a Catalyst: Borylated Isoxazoles via B-O σ-Bond Addition.

Herein we report an oxyboration reaction with activated substrates that employs B-O σ bond additions to C-C π bonds to form borylated isoxazoles, which are potential building blocks for drug discovery. Although this reaction can be effectively catalyzed by gold, it is the first example of uncatalyzed oxyboration of C-C π bonds by B-O σ bonds--and only the second example that is catalyzed. This oxyboration reaction is tolerant of groups incompatible with alternative lithiation/borylation and palladium-catalyzed C-H activation/borylation technologies for the synthesis of borylated isoxazoles.

Kinetic Study of Carbophilic Lewis Acid Catalyzed Oxyboration and the Noninnocent Role of Sodium Chloride.

In the present study, the oxyboration reaction catalyzed by IPrAuTFA in the presence and absence of NaTFA has been examined with kinetic studies, mass spectrometry, and 1H NMR and 11B NMR spectroscopy. Data from monitoring the reactions over the temperature range from 30 to 70 °C, the catalyst range from 1.3 to 7.5 mol %, and the NaTFA additive range from 2.5 to 30 mol % suggests a mechanism that involves rate-determining catalyst generation. Data from additive studies that replaced NaTFA with NaBARF (BARF = tetrakis[3,5-bis(trifluoromethyl)phenyl]borate) or Bu4NTFA as an alternative additive suggest that catalyst quenching from residual NaCl remaining from a one-pot substrate synthesis/reaction method is the cause of this effect, despite the low solubility of this NaCl byproduct in toluene. Material produced through an alternative, sodium chloride free substrate synthesis exhibited faster reaction rates, consistent with a change in rate-determining step that depended on the substrate synthesis route.

Deficiencies in the endoplasmic reticulum (ER)-membrane protein Gab1p perturb transfer of glycosylphosphatidylinositol to proteins and cause perinuclear ER-associated actin bar formation.

The essential GAB1 gene, which encodes an endoplasmic reticulum (ER)-membrane protein, was identified in a screen for mutants defective in cellular morphogenesis. A temperature-sensitive gab1 mutant accumulates complete glycosylphosphatidylinositol (GPI) precursors, and its temperature sensitivity is suppressed differentially by overexpression of different subunits of the GPI transamidase, from strong suppression by Gpi8p and Gpi17p, to weak suppression by Gaa1p, and to no suppression by Gpi16p. In addition, both Gab1p and Gpi17p localize to the ER and are in the same protein complex in vivo. These findings suggest that Gab1p is a subunit of the GPI transamidase with distinct relationships to other subunits in the same complex. We also show that depletion of Gab1p or Gpi8p, but not Gpi17p, Gpi16p, or Gaa1p causes accumulation of cofilin-decorated actin bars that are closely associated with the perinuclear ER, which highlights a functional interaction between the ER network and the actin cytoskeleton.