Variation in C - reactive protein response according to host and mycobacterial characteristics in active tuberculosis.

BACKGROUND: The C - reactive protein (CRP) response is often measured in patients with active tuberculosis (TB) yet little is known about its relationship to clinical features in TB, or whether responses differ between ethnic groups or with different Mycobacterium tuberculosis (M.tb) strain types. We report the relationship between baseline serum CRP prior to treatment and disease characteristics in a metropolitan population with TB resident in a low TB incidence region. METHODS: People treated for TB at four London, UK sites between 2003 and 2014 were assessed and data collected on the following characteristics: baseline CRP level; demographics (ethnicity, gender and age); HIV status; site of TB disease; sputum smear (in pulmonary cases) and culture results. The effect of TB strain-type was also assessed in culture-positive pulmonary cases using VNTR typing data. RESULTS: Three thousands two hundred twenty-two patients were included in the analysis of which 72 % had a baseline CRP at or within 4 weeks prior to starting TB treatment. CRP results were significantly higher in culture positive cases compared to culture negative cases: median 49 mg/L (16-103 mg/L) vs 19 mg/L (IQR 5-72 mg/L), p = <0.001. In those with pulmonary disease, smear positive cases had a higher CRP than smear negative cases: 67 mg/L (31-122 mg/L) vs 24 mg/L (7-72 mg/L), p < 0.001. HIV positive cases had higher baseline CRPs than HIV negative cases: 75 mg/L (26-136 mg/L) vs 37 mg/L (10-88 mg/L), p <0.001. Differing sites of disease were associated with differences in baseline CRP: locations that might be expected to have a high mycobacterial load (e.g. pulmonary disease and disseminated disease) had a significantly higher CRP than those such as skin, lymph node or CNS disease, where the mycobacterial load is typically low in HIV negative subjects. In a multivariable log-scale linear regression model adjusting for host characteristics and M.tb strain type, infection with the East African Indian strain was associated with significantly lower baseline-CRP (fold-change in CRP 0.51 (0.34-0.77), p < 0.01). CONCLUSIONS: Host and mycobacterial factors are strongly associated with baseline CRP response in tuberculosis. This analysis suggests that there are important differences in innate immune response according to ethnicity, Mtb strain type and site of disease. This may reflect differing mycobacterial loads or host immune responses.

A regio- and stereoselective ω-transaminase/monoamine oxidase cascade for the synthesis of chiral 2,5-disubstituted pyrrolidines.

Biocatalytic approaches to the synthesis of optically pure chiral amines, starting from simple achiral building blocks, are highly desirable because such motifs are present in a wide variety of important natural products and pharmaceutical compounds. Herein, a novel one-pot ω-transaminase (TA)/monoamine oxidase (MAO-N) cascade process for the synthesis of chiral 2,5-disubstituted pyrrolidines is reported. The reactions proceeded with excellent enantio- and diastereoselectivity (>94 % ee; >98 % de) and can be performed on a preparative scale. This methodology exploits the complementary regio- and stereoselectivity displayed by both enzymes, which ensures that the stereogenic center established by the transaminase is not affected by the monoamine oxidase, and highlights the potential of this multienzyme cascade for the efficient synthesis of chiral building blocks.

Structures of a γ-aminobutyrate (GABA) transaminase from the s-triazine-degrading organism Arthrobacter aurescens TC1 in complex with PLP and with its external aldimine PLP-GABA adduct.

Two complex structures of the γ-aminobutyrate (GABA) transaminase A1R958 from Arthrobacter aurescens TC1 are presented. The first, determined to a resolution of 2.80 Å, features the internal aldimine formed by reaction between the ℇ-amino group of Lys295 and the cofactor pyridoxal phosphate (PLP); the second, determined to a resolution of 2.75 Å, features the external aldimine adduct formed between PLP and GABA in the first half-reaction. This is the first structure of a microbial GABA transaminase in complex with its natural external aldimine and reveals the molecular determinants of GABA binding in this enzyme.

A fast and sensitive assay for measuring the activity and enantioselectivity of transaminases.

A fast and sensitive method for screening transaminase activity and enantioselectivity, using D- and L-amino acid oxidases, allows new amine substrates to be rapidly identified.

Incidence and reinfection rates of genital chlamydial infection among women aged 16-24 years attending general practice, family planning and genitourinary medicine clinics in England: a prospective cohort study by the Chlamydia Recall Study Advisory Group.

BACKGROUND: In England, screening for genital chlamydial infection has begun; however, screening frequency for women is not yet determined. AIM: To measure chlamydia incidence and reinfection rates among young women to suggest screening intervals. METHODS: An 18-month prospective cohort study of women aged 16-24 years recruited from general practices, family planning clinics and genitourinary medicine (GUM) clinics: baseline-negative women followed for incidence and baseline-positive women for reinfection; urine tested every 6 months via nucleic acid amplification; and behavioural data collected. Extra test and questionnaire completed 3 months after initial positive test. Factors associated with infection and reinfection investigated using Cox regression stratified by healthcare setting of recruitment. RESULTS: Chlamydia incidence was mean (95% CI) 4.9 (2.7 to 8.8) per 100 person-years (py) among women recruited from general practices, 6.4 (4.2 to 9.8) from family planning clinics and 10.6 (7.4 to 15.2) from GUM clinics. Incidence was associated with young age, history of chlamydial infection and acquisition of new sexual partners. If recently acquiring new partners, condom use at last sexual intercourse was independently associated with lower incidence. Chlamydia reinfection was mean (95% CI) 29.9 (19.7 to 45.4) per 100/person-year from general practices, 22.3 (15.6 to 31.8) from family planning clinics and 21.1 (14.3 to 30.9) from GUM clinics. Factors independently associated with higher reinfection rates were acquisition of new partners and failure to treat all partners. CONCLUSIONS: Sexual behaviours determined incidence and reinfection, regardless of healthcare setting. Our results suggest annual screening of women aged 16-24 years who are chlamydia negative, or sooner if partner change occurs. Rescreening chlamydia-positive women within 6 months of baseline infection may be sensible, especially if partner change occurs or all partners are not treated.

A study of gender relationships and their association with the practice of safe sex by women who call into the National HIV/STD helpline

The heterosexual spread of HIV/AIDS is greatly increased by the inability of many women to protect themselves from the disease. Applying a gender aware approach to combat the HIV/AIDS epidemic is to examine how the social relationships between women and men reveal new perspectives on the epidemic and to provide new responses to it. A study was done of women who called into the National HIV/STD Helpline. The objectives of the study were to determine the socio-demographic distribution of callers, to determine factors that contributed to knowledge and practice of safe sex, to determine the role of gender relationships in the practice of safe sex and finally to determine the links between risk status and personal behaviour. A convenience sample was taken. A total of fifty women were interviewed. Significant results from the study centered around gender relationships and risk taking behaviour. Risk taking activities such as multiple partners, irregular condom use, and self reported incidence of STDs were an indicator of the reality of risk and need for intervention of this group. General views of callers were that they had a "good relationship" with their partners, however, 56 percent of callers stated that their partner would become angry at request of a condom. Seventy-two percent of the callers stated that they were at-risk for HIV/AIDS. Suspicion of out-side heterosexual or bisexual relationships were seen as the main reasons for perception of risk. Current studies have shown that women of all ages, socio-economic backgrounds are being affected with HIV/AIDS. Having control over her body, feeling empowered within her sexual relationships enable women to practice and request safe sex. Producing optimal behaviour change is the goal of Haelth Education and Promotion. Issues of gender awareness and gender relationships must be instituted into programmes for change to take place. (AU)