Diabetic macular ischaemia- a new therapeutic target?

Diabetic macular ischaemia (DMI) is traditionally defined and graded based on the angiographic evidence of an enlarged and irregular foveal avascular zone. However, these anatomical changes are not surrogate markers for visual impairment. We postulate that there are vascular phenotypes of DMI based on the relative perfusion deficits of various retinal capillary plexuses and choriocapillaris. This review highlights several mechanistic pathways, including the role of hypoxia and the complex relation between neurons, glia, and microvasculature. The current animal models are reviewed, with shortcomings noted. Therefore, utilising the advancing technology of optical coherence tomography angiography (OCTA) to identify the reversible DMI phenotypes may be the key to successful therapeutic interventions for DMI. However, there is a need to standardise the nomenclature of OCTA perfusion status. Visual acuity is not an ideal endpoint for DMI clinical trials. New trial endpoints that represent disease progression need to be developed before irreversible vision loss in patients with DMI. Natural history studies are required to determine the course of each vascular and neuronal parameter to define the DMI phenotypes. These DMI phenotypes may also partly explain the development and recurrence of diabetic macular oedema. It is also currently unclear where and how DMI fits into the diabetic retinopathy severity scales, further highlighting the need to better define the progression of diabetic retinopathy and DMI based on both multimodal imaging and visual function. Finally, we discuss a complete set of proposed therapeutic pathways for DMI, including cell-based therapies that may provide restorative potential.     

Gender Identity and Non-Binary Presentations in Adolescents Attending Two Specialized Services in Italy

BackgroundRecently, the variability and heterogeneity of gender presentations in transgender youths have gained significant attention worldwide. Alongside this, specialized gender services have reported an increase in referrals of youths reporting non-binary identities. In Italy, studies investigating gender identity and expression in gender non-conforming youths are lacking, as are data regarding the non-binary population.AimThe present study aimed at dimensionally exploring how transgender and non-binary Italian adolescents identify and express their gender.OutcomesGender expression in trans binary youths and non-binary youths.MethodsThe Gender Diversity Questionnaire (GDQ; Twist & de Graaf, 2019) was used to investigate gender identity, gender fluidity, and gender expression in a sample of 125 adolescent patients from the Gender Identity Development Service (SAIFIP) in Rome and the Gender Incongruence Unit of the Careggi Hospital in Florence, between April 2019–June 2021.ResultsThe majority of participants (74.4%) identified as trans* binary and the remaining (25.6%) participants identified as non-binary. Trans binary participants reported a stable gender identity, whereas non-binary participants reported a more fluid gender identity across time and contexts. Almost all participants rated external appearance as important to their gender expression, yet trans binary participants attributed more importance to the body in this respect. Body discomfort and pubertal stage emerged as the most influential factors in participants’ experiences of gender. Participants who were assigned male at birth expressed significantly more desire for puberty blockers, whereas those who were assigned female at birth had a stronger desire to engage in breast/chest surgery. Non-binary participants sought different medical interventions relative to trans binary participants.Clinical ImplicationsThese results may be useful for clinicians working with transgender youths as they provide awareness regarding the features of young people who identify within and outside of binary constructions of gender.Strengths & LimitationsThis study provides useful data in gaining insight into understanding the variety of experiences and challenges of gender non-conforming youths. However as the sample was recruited from specialized services, it may not represent the entire gender non-conforming population in Italy.ConclusionThe results describe the range of gender identities and expressions among gender non-conforming youths attending gender specialized services in Italy, thereby improving our understanding of the variety of identities experienced and the specific medical needs of both trans binary and non-binary adolescents.Mirabella M, Piras I, Fortunato A, et al. Gender Identity and Non-Binary Presentations in Adolescents Attending Two Specialized Services in Italy. J Sex Med 2022;19:1035–1048.     

Molecular detection of Orientia tsutsugamushi strains circulating in Nagaland

The antigenic heterogeneity of Orientia in India is still unknown in many disease endemic areas. The present study aims to characterize the strains of O. tsutsugamushi circulating in Nagaland, Northeast India. Two patients clinically diagnosed with ST and hospitalized in Mon district hospital, Nagaland were identified from whom eschar tissues were collected. Both patients demonstrated antibodies against O. tsutsugamushi along with positive PCR amplification for 56 ?kDa gene. The prototype strain TA763 shared 90.4% homology with the sequences. Both the sequences formed a distinctive cluster demonstrating 100% similarity with strains identified from Thailand, Vietnam, China and southern parts of India.     

Progress towards a vaccine against Ebola to meet emergency medical countermeasure needs

The Ebola virus epidemic in West Africa proved to be the largest in the history of filovirus outbreaks, causing the World Health Organization to declare a public health emergency of international concern in August of 2014. In collaboration with domestic and international partners, the Biomedical Advanced Research and Development Authority (BARDA) initiated several vaccine development projects in support of the overall response efforts. The urgency associated with the epidemic triggered the clinical evaluation of lead vaccine candidates starting in late 2014. Here we will discuss development of the lead vaccine candidates for Ebola virus, specifically Zaire ebolavirus.     

Adjuvanted leptospiral vaccines: Challenges and future development of new leptospirosis vaccines

Leptospirosis is a neglected infectious disease of global importance. Vaccination is the most viable strategy for the control of leptospirosis, but in spite of efforts for the development of an effective vaccine against the disease, few advances have been made, and to date, bacterin is the only option for prevention of leptospirosis. Bacterins are formulations based on inactivated leptospires that present a series of drawbacks, such as serovar-dependence and short-term immunity. Therefore, bacterins are not widely used in humans, and only Cuba, France and China have these vaccines licensed for at-risk populations. The development of recombinant DNA technology emerges as an alternative to solve the problem. Recombinant protein-based vaccines or DNA vaccines seem to be an attractive strategy, but the use of adjuvants is critical for achievement of a protective immune response. Adjuvants are capable of enhancing and/or modulating immune responses by exposing antigens to antigen-presenting cells. In the last years, several components have been tested as adjuvants, such as aluminum salts, oil based-emulsion adjuvants, bacteria-derived components and liposomes. This review highlights the use of adjuvants in the multiple vaccine approaches that have been used for leptospirosis and their most important immunological aspects. Immune response data generated by these strategies can contribute to the understanding of the immune mechanisms involved in protection against leptospirosis, and consequently, the development of effective vaccines against this disease. This is the first review on leptospiral vaccines focusing on adjuvant aspects.