Autocrine and Paracrine Secretion of Vascular Endothelial Growth Factor in the Pre-Hypoxic Diabetic Retina

Vascular endothelial growth factor (VEGF) is well established as the main agent responsible for vascular leakage and angiogenesis in the diabetic retina. While VEGF can have positive effects on hyperglycemia stressed retinal tissues, it also plays a role in events progressing to the oxygen- stressed, i.e. hypoxic, diabetic retina. Some VEGF makes its way to the retina from systemic sources and some is produced locally within the eye. Hyperglycemia, oxidants, inflammation, and advanced glycation end-products are all stimulants to VEGF production, both in the hypoxic and the pre-hypoxic retina. Endothelial cells, pericytes, Müller cells, microglia, astrocytes, retinal pigment epithelium and neurons have all been known to produce VEGF at some point in retinal development or in disease. Excessive VEGF production in the early diabetic retina can lead to retinal exposure or mechanisms which exacerbate further damage. While Müller cells are likely the most significant producer of VEGF in the pre-hypoxic retina, other VEGF producing cells may also play a role due to their proximity to vessels or neurons. Study of the release of VEGF by retinal cells in hyperglycemia conditions, may help identify targets for early treatment and prevent the serious consequences of diabetic retinopathy

Current Scenario of Clinical Cancer Research in Latin America and the Caribbean

In Latin America and the Caribbean (LAC), progress has been made in some national and regional cancer control initiatives, which have proved useful in reducing diagnostic and treatment initiation delays. However, there are still significant gaps, including a lack of oncology clinical trials. In this article, we will introduce the current status of the region’s clinical research in cancer, with a special focus on academic cancer research groups and investigator-initiated research (IIR) initiatives. Investigators in LAC have strived to improve cancer research despite drawbacks and difficulties in funding, regulatory timelines, and a skilled workforce. Progress has been observed in the representation of this region in clinical trial development and conduct, as well as in scientific productivity. However, most oncology trials in the region have been sponsored by pharmaceutical companies, highlighting the need for increased funding from governments and private foundations. Improvements in obtaining and/or strengthening the LAC cancer research group’s financing will provide opportunities to address cancer therapies and management shortcomings specific to the region. Furthermore, by including this large, ethnic, and genetically diverse population in the world’s research agenda, one may bridge the gap in knowledge regarding the applicability of results of clinical trials now mainly conducted in populations from the Northern Hemisphere

Adjuvant endocrine therapy for premenopausal women with breast cancer: Patient adherence and physician prescribing practices in Mexico

Background: In resource-constrained settings, data regarding breast cancer patients' adherence to endocrine therapy (ET) and physicians’ prescribing practices is limited. This study aims to decrease this knowledge gap in a real-world clinical practice. Methods: Premenopausal women with stage 0-III hormone-sensitive breast cancer and receiving adjuvant ET during the past 1–5 years were identified in three Mexican referral centers. Participants' self-reported ET compliance, clinicopathologic characteristics, ET-related knowledge and beliefs, experienced adverse effects, social support, and patient-physician relationships were evaluated. Physician ET prescribing practices were compared with the gold standard according to international and national guidelines to assess clinicians’ adherence to standard-of-care prescription. Results: In total, 95/132 (72%) and 35/132 (27%) participants reported complete and acceptable adherence, respectively. Incomplete adherence was mainly attributed to forgetfulness, adverse effects, and unwillingness to take ET. Being employed/studying (p = 0.042), worrying about long-term ET use (p = 0.031), and experiencing >7 ET-related symptoms (p = 0.018) were associated with incomplete adherence. Guideline-endorsed regimens were prescribed in 84/132 (64%) patients, while the rest should have undergone ovarian function suppression (OFS) but instead received tamoxifen monotherapy. Conclusions: Premenopausal Mexican women self-report remarkably high rates of adequate ET adherence. However, a considerable proportion misses ≥1 doses/month, usually because of forgetfulness. Notably, only 64% receive standard-of-care ET due to suboptimal prescription of OFS. Interventions that remind patients to take their ET, refine physicians’ knowledge on the importance of OFS in high-risk patients, and increase access to OFS could prove pivotal to enhance optimal ET implementation and adherence, which could translate into improved patient outcomes

Revisão anatômica do seio venoso sagital dorsal no crânio de cães braquicéfalos Anatomic features of the dorsal venous sinus in skull of brachycephalous dogs

Os seios venosos do crânio realizam a drenagem do cérebro e da medula espinhal, a fim de manter a homeostasia e o perfeito funcionamento do sistema nervoso central. Lesões na rede venosa cerebral podem causar déficits severos tais como hemiplegia, hemorragia, coma e morte. Os seios venosos são importantes pontos de referência para a realização de técnicas cirúrgicas de acesso ao cérebro. Este estudo visou analisar o trajeto do seio venoso sagital dorsal no crânio de cães braquicéfalos. Os animais braquicéfalos possuem crânios curtos e com características biométricas específicas. Foram utilizados 8 crânios de cães da raça Boxer, que foram submetidos à injeção de látex com pigmento corado e sulfato de bário. Após a perfusão, foram feitas radiografias contrastadas e imagens de tomografia computadorizada para relacionar o seio venoso com a estrutura óssea e dimensões relativas da calota craniana. Os crânios apresentaram índice cefálico (IC) médio de 91,24&plusmn;8,34mm e índice crânio-facial (ICF) médio de 2,89&plusmn;0,23mm. As mensurações do seio venoso sagital dorsal, relativas à calota craniana, apresentaram os seguintes valores médios: Área = 10,18&plusmn;4,69mm²; D1 = 11,84&plusmn;2,35mm; D2 = 19,57&plusmn;2,61mm; D3 = 17,88&plusmn;2,31mm; D4 = 25,32&plusmn;5,68mm; e D5= 24,84&plusmn;4,40mm.<br>The dorsal venous sinuses of the Dura mater perform the cerebral and spinal cord drainage to keep homeostasis of the Central Nervous System. Injuries in the cerebral venous network may cause severe deficits, including hemiplegia, hemorrhage, coma and death. The main landmark for neurologic surgery is the Dura mater venous sinus. The aim of this study is to analyse the pathway of the Sinus sagittalis dorsalis in the brachycephalous skull, as the brachycephalous dogs have specific characteristics. The skulls were taken from 8 Boxer dogs and venous perfusion with latex and barium sulfate solution was performed. After the perfusion, radiographies and tomographies were obtained to relate the dorsal sagittal sinus and the skull averages. The cephalic index showed mean values of 91.24&plusmn;8.34cm, and the cranio-facial index was 2.89&plusmn;0.23cm. The venous sinus mensuration interface to the skull was: Área = 10.18&plusmn;4.69mm²; D1 = 11.84&plusmn;2.35mm; D2 = 19.57&plusmn;2.61mm; D3 = 17.88&plusmn;2.31mm; D4 = 25.32&plusmn;5.68mm e D5 = 24.84&plusmn;4.40mm

Highlights 2020: framing health stories

Despite the difficulties of this pandemic year, The Lancet received fascinating and varied entries for our Highlights 2020 photography competition. 15 striking photographs were selected for publication in this issue. Each picture captures a unique moment, highlighting a health story

Cancer control in Latin America and the Caribbean: Recent advances and opportunities to move forward

The increasing burden of cancer represents a substantial problem for Latin America and the Caribbean. Two Lancet Oncology Commissions in 2013 and 2015 highlighted potential interventions that could advance cancer care in the region by overcoming existing challenges. Areas requiring improvement included insufficient investment in cancer control, non-universal health coverage, fragmented health systems, inequitable concentration of cancer services, inadequate registries, delays in diagnosis or treatment initiation, and insufficient palliative services. Progress has been made in key areas but remains uneven across the region. An unforeseen challenge, the COVID-19 pandemic, strained all resources, and its negative effect on cancer control is expected to continue for years. In this Series paper, we summarise progress in several aspects of cancer control since 2015, and identify persistent barriers requiring commitment of additional resources to reduce the cancer burden in Latin America and the Caribbean