Australian sexually transmitted infection (STI) management guidelines for use in primary care 2022 update.

The 'Australian Sexually Transmitted Infection (STI) Management Guidelines For Use In Primary Care' (www.sti.guidelines.org.au ) provide evidence-based, up-to-date guidance targeted at use in primary care settings. A major review of the guidelines was undertaken in 2020-22. All content was reviewed and updated by a multi-disciplinary group of clinical and non-clinical experts, and assessed for appropriateness of recommendations for key affected populations and organisational and jurisdictional suitability. The guidelines are divided into six main sections: (1) standard asymptomatic check-up; (2) sexual history; (3) contact tracing; (4) STIs and infections associated with sex; (5) STI syndromes; and (6) populations and situations. This paper highlights important aspects of the guidelines and provides the rationale for significant changes made during this major review process.

Position statement on the hormonal management of adult transgender and gender diverse individuals.

INTRODUCTION: Rising demand for gender-affirming hormone therapy mandates a need for more formalised care of transgender and gender diverse (TGD) individuals in Australia. Estimates suggest that 0.1-2.0% of the population are TGD, yet medical education in transgender health is lacking. We aim to provide general practitioners, physicians and other medical professionals with specific Australian recommendations for the hormonal and related management of adult TGD individuals. MAIN RECOMMENDATIONS: Hormonal therapy is effective at aligning physical characteristics with gender identity and in addition to respectful care, may improve mental health symptoms. Masculinising hormone therapy options include transdermal or intramuscular testosterone at standard doses. Feminising hormone therapy options include transdermal or oral estradiol. Additional anti-androgen therapy with cyproterone acetate or spironolactone is typically required. Treatment should be adjusted to clinical response. For biochemical monitoring, target estradiol and testosterone levels in the reference range of the affirmed gender. Monitoring is suggested for adverse effects of hormone therapy. Preferred names in use and pronouns should be used during consultations and reflected in medical records. While being TGD is not a mental health disorder, individualised mental health support to monitor mood during medical transition is recommended. CHANGES IN MANAGEMENT AS RESULT OF THIS POSITION STATEMENT: Gender-affirming hormone therapy is effective and, in the short term, relatively safe with appropriate monitoring. Further research is needed to guide clinical care and understand long term effects of hormonal therapies. We provide the first guidelines for medical practitioners to aid the provision of gender-affirming care for Australian adult TGD individuals.

Structural changes of Zn(II)bleomycin complexes when bound to DNA hairpins containing the 5'-GT-3' and 5'-GC-3' binding sites studied through NMR spectroscopy.

Bleomycins are antitumor antibiotics that can chelate a metal center and cause site-specific DNA cleavage at 5'-Gpyrimidine-3' regions of DNA. These antibiotics are successful in the treatment of various cancers, but are known to cause pulmonary fibrosis to patients under bleomycin regimes. Substantial research has resulted in the development of over 300 bleomycin analogs, aiming to improve the therapeutic index of the drug. Previous studies have proposed that the lung toxicity caused by bleomycin is related to the C-terminal regions of these drugs, which have been shown to closely interact with DNA in metal-bleomycin-DNA complexes. Some of the research studying metallo-bleomycin-DNA interactions have suggested three different binding modes of the metal form of the drug to DNA, including total and/or partial intercalation, and minor groove binding. However, there is still lack of consensus regarding this matter, and solid conclusions on the subject have not yet been established. Previously we investigated the diverse levels of disruption caused to DNA hairpins containing 5'-GC-3' and 5'-GT-3' binding sites, which are consequence of the binding of bleomycins with different C-termini. The results of these investigation indicate that both the DNA-binding site and the bleomycin C-termini have an impact on the final conformations of drug and target. The present study focuses on the structural alterations exhibited by Zn(II)bleomycin-A2, -B2, -A5 and Zn(II)peplomycin upon binding to DNA hairpins containing 5'-GC-3' and 5'-GT-3' binding sites. Evidence that each Zn(II)bleomycin is structurally affected depending on both its C-terminus and the DNA-binding site present in the hairpin is provided.

Interaction of Zn(II)bleomycin-A2 and Zn(II)peplomycin with a DNA hairpin containing the 5'-GT-3' binding site in comparison with the 5'-GC-3' binding site studied by NMR spectroscopy.

Bleomycins are a group of glycopeptide antibiotics synthesized by Streptomyces verticillus that are widely used for the treatment of various neoplastic diseases. These antibiotics have the ability to chelate a metal center, mainly Fe(II), and cause site-specific DNA cleavage. Bleomycins are differentiated by their C-terminal regions. Although this antibiotic family is a successful course of treatment for some types of cancers, it is known to cause pulmonary fibrosis. Previous studies have identified that bleomycin-related pulmonary toxicity is linked to the C-terminal region of these drugs. This region has been shown to closely interact with DNA. We examined the binding of Zn(II)peplomycin and Zn(II)bleomycin-A2 to a DNA hairpin of sequence 5'-CCAGTATTTTTACTGG-3', containing the binding site 5'-GT-3', and compared the results with those obtained from our studies of the same MBLMs bound to a DNA hairpin containing the binding site 5'-GC-3'. We provide evidence that the DNA base sequence has a strong impact in the final structure of the drug-target complex.

NMR study of the effects of some bleomycin C-termini on the structure of a DNA hairpin with the 5'-GC-3' binding site.

The antibiotics known as bleomycins constitute a family of natural products clinically employed for the treatment of a wide spectrum of cancers. The drug acts as an antitumor agent by virtue of the ability of a metal complex of the antibiotic to cleave DNA. Bleomycins are differentiated by their C-terminal regions. Previous structural studies involving metal-bleomycin-DNA triads have allowed the identification of the bithiazole-(C-terminus substituent) segment in this molecule as the one that most closely interacts with DNA. Three different modes of binding of metallo-bleomycins to DNA (partial or total intercalation of the bithiazole unit between DNA bases, or binding to the minor groove) have been proposed in the literature. The therapeutic use of bleomycin is frequently associated with the development of pulmonary fibrosis. The severity of this side effect has been attributed to the C-terminus of the antibiotic by some researchers. The degree of pulmonary toxicity of bleomycin-A2 and -A5, were found to be higher than those of bleomycin-B2 and peplomycin. Since the introduction of Blenoxane to clinical medicine in 1972, attempts have been made at modifying the basic bleomycin structure at the C-terminus to improve its therapeutic index. However, the pharmacological and toxicological importance of particular C-termini on bleomycin remains unclear. The present study was designed to determine the effect of Zn(II)bleomycin-A2, -A5, -B2, and Zn(II)peplomycin on the structure of a DNA hairpin containing the 5'-GC-3' binding site. We provide evidence that different Zn(II)bleomycins affect the structure of the tested DNA segment in different fashions.

A randomised trial of two techniques for bottle feeding preterm infants.

AIM: Preterm infants begin the transition from gastric tube feeds to sucking feeds around 34 weeks' postmenstrual age. We compared physiological stability in two bottle feeding positions, cradle hold versus side lying in preterm infants. METHODS: Randomised crossover trial of infants <34 weeks' gestation at birth, ≥34 weeks' postmenstrual age at study and receiving at least two sucking feeds/day. Two feeds were studied on successive days. A pulse oximeter measured oxygen saturation (SpO2) and heart rate (HR) before, during and 30 min after feeds. Continuous data were compared using paired t-tests and proportions using chi squared. RESULTS: Twenty-five study infants were mean (standard deviation (SD)) 37 (2.4) weeks' post-menstrual age and 2740 (589) g at study. There was little difference in mean (SD) SpO2 during feeds between the cradle-hold and side-lying position 94 (6) % versus 95 (6) %, respectively (P = 0.55, confidence interval (CI) -1.4, 5.4). During feeds, 17/25 (68%) experienced a period of SpO2 <80% in the cradle-hold position compared with 14/25 (56) % in the side-lying position (P = 0.26, CI 0.68, 4.10). There were no significant differences in the mean HR or number of episodes of bradycardia HR <100 bpm. There was a trend towards infants consuming a smaller mean (SD) proportion of their feed in the cradle-hold position compared with the side-lying position, 82 (25) % versus 87 (20) % (P = 0.08, CI -0.64, 10.00). CONCLUSIONS: There was little difference in infants' physiological stability between the two bottle feeding positions. Both methods may be appropriate for the transition from gastric tube to sucking feeds in preterm infants.

Up close and personal: poverty and human development.

POVERTY AND HEALTH ARE INEXTRICABLY LINKED: poverty diminishes access to health care (whether through reduced ability to pay, a lack of knowledge about when to seek health care or a lack of adequate services within reach), increases exposure to disease and other illness (for example, through exposure to dangerous workplaces), and is related to reduced access to clean water, housing and sanitation.