Background Little information is available about the geo-economic variations in demographics, management, and outcomes of patients with acute respiratory distress syndrome (ARDS). We aimed to characterise the effect of these geo-economic variations in patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE). Methods LUNG SAFE was done during 4 consecutive weeks in winter, 2014, in a convenience sample of 459 intensivecare units in 50 countries across six continents. Inclusion criteria were admission to a participating intensive-care unit (including transfers) within the enrolment window and receipt of invasive or non-invasive ventilation. One of the trial's secondary aims was to characterise variations in the demographics, management, and outcome of patients with ARDS. We used the 2016 World Bank countries classification to define three major geo-economic groupings, namely European high-income countries (Europe-High), high-income countries in the rest of the world (rWORLD-High), and middle-income countries (Middle). We compared patient outcomes across these three groupings. LUNG SAFE is registered with ClinicalTrials.gov, number NCT02010073. Findings Of the 2813 patients enrolled in LUNG SAFE who fulfilled ARDS criteria on day 1 or 2, 1521 (54%) were recruited from Europe-High, 746 (27%) from rWORLD-High, and 546 (19%) from Middle countries. We noted significant geographical variations in demographics, risk factors for ARDS, and comorbid diseases. The proportion of patients with severe ARDS or with ratios of the partial pressure of arterial oxygen (PaO 2) to the fractional concentration of oxygen in inspired air (F I O 2) less than 150 was significantly lower in rWORLD-High countries than in the two other regions. Use of prone positioning and neuromuscular blockade was significantly more common in Europe-High countries than in the other two regions. Adjusted duration of invasive mechanical ventilation and length of stay in the intensive-care unit were significantly shorter in patients in rWORLD-High countries than in Europe-High or Middle countries. High gross national income per person was associated with increased survival in ARDS; hospital survival was significantly lower in Middle countries than in Europe-High or rWORLD-High countries. Interpretation Important geo-economic differences exist in the severity, clinician recognition, and management of ARDS, and in patients' outcomes. Income per person and outcomes in ARDS are independently associated.

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Cancer is the second most common culprit of mortality in the United States and epithelial carcinomas are considered as one of the most predominant types of cancer. The association between epithelial cancers and paired-box gene 8 (PAX8) has been studied significantly before. PAX8 belongs to the paired-box gene family, which plays an important role in the organogenesis of different body organ systems, especially the thyroid gland, the renal system, and the Müllerian system. Immunohistochemical staining is being used to detect PAX8 expression in different epithelial cancers and differentiate them from PAX8-negative tumors. In follicular, papillary, and anaplastic thyroid carcinomas, targeting the PAX8/peroxisome proliferatoractivated receptors (PPARs) fusion protein is being considered as a potential mechanism for therapy. Moreover, because of its high expression in primary ovarian cancers, PAX8 is being considered as a target for ovarian cancer treatment as well. More studies are needed to test the possibility of using PAX8 as a possible target for managing endometrial carcinomas. In this article, we review the functions of the PAX8 gene, how its mutations lead to the development of certain epithelial carcinomas, how it can be used as a diagnostic or a prognostic marker, and its potential as a therapeutic target for these cancers.

Kisspeptin is a neuropeptide that plays a significant role in human reproduction by its action on the hypothalamic-pituitary-gonadal (HPG) axis and functions through a G-protein-coupled receptor called Gprotein-coupled receptor 54/kisspeptin 1 receptor (GPR54/KISS1R). It is encoded by the kisspeptin 1 (KISS1) gene that is mainly expressed in the hypothalamus. Kisspeptins are also recognized as vital aspects of maturation and proper function of the reproductive system in both males and females. It also plays its role in the onset of puberty, sexual patterns, desires, ovum development in women, sperm quality in men, feedback mechanisms, pregnancy, and lactation. Studies proved the pathological role of kisspeptin dysregulation in disorders like polycystic ovarian syndrome (PCOS) and infertility. Mutations in the KISS1 gene also contribute to precocious puberty or hypogonadotropic hypogonadism, depending upon the nature of mutations. Levels of kisspeptin also aid in the identification of a few pregnancy-related complications like preeclampsia, intrauterine growth restriction, and act as a marker of miscarriage. Due to the wide range of effects that kisspeptin has on the reproductive axis, investigations are being carried out to develop it as a diagnostic marker, treat diseases like hypogonadism and PCOS, and solve infertility issues.

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