Houmannfranco0619

In drug development, a crucial step is the transition of a company from preclinical stages to human trials the so-called 'Valley-of-Death' (VoD) that most efforts do not survive. Here, we analyzed how the valuations of biotech companies in the life science sector change as they cross this valley. Their average valuation increased significantly (87%) when crossing the VoD no later than their fourth funding round. However, companies that received more than four funding rounds saw significantly lower average valuations. Similarly, the volume of website traffic for companies that received no more than four preclinical funding rounds was significantly higher than companies receiving more than four preclinical funding rounds, whereas the number of patents was unrelated to the likelihood of a company of crossing the VoD.The management of chronic noncancer pain (CNCP) with chronic opioid therapy (COT) is controversial. There is a lack of consensus on how COT is defined resulting in unclear clinical guidance. This scoping review identifies and evaluates evolving COT definitions throughout the published clinical and scientific literature. Databases searched included PubMed, Embase, and Web of Science. A total of 227 studies were identified from 8,866 studies published between January 2000 and July 2019. COT definitions were classified by pain population of application and specific dosage/duration definition parameters, with results reported according to PRISMA-ScR. Approximately half of studies defined COT as "days' supply duration >90 days" and 9.3% defined as ">120 days' supply," with other days' supply cut-off points (>30, >60, or >70) each appearing in 90 days' supply." The most recent literature trends toward shorter duration criteria, suggesting that contemporary COT definitions are increasingly conservative. PERSPECTIVE This study summarized the most common, current definition criteria for chronic opioid therapy (COT) and recommends adoption of consistent definition criteria to be utilized in practice and research. The most recent literature trends toward shorter duration criteria overall, suggesting that COT definition criteria are increasingly stringent.Oxylipins are lipid peroxidation products that participate in nociceptive, inflammatory, and vascular responses to injury. Effects of oxylipins depend on tissue-specific differences in accumulation of precursor polyunsaturated fatty acids and the expression of specific enzymes to transform the precursors. The study of oxylipins in nociception has presented technical challenges leading to critical knowledge gaps in the way these molecules operate in nociception. We applied a systems-based approach to characterize oxylipin precursor fatty acids, and expression of genes coding for proteins involved in biosynthesis, transport, signaling and inactivation of pro- and antinociceptive oxylipins in pain circuit tissues. We further linked these pathways to nociception by demonstrating intraplantar carrageenan injection induced gene expression changes in oxylipin biosynthetic pathways. We determined functional-biochemical relevance of the proposed pathways in rat hind paw and dorsal spinal cord by measuring basal and stimulated levels of oxylipins throughout the time-course of carrageenan-induced inflammation. Finally, when oxylipins were administered by intradermal injection we observed modulation of nociceptive thermal hypersensitivity, providing a functional-behavioral link between oxylipins, their molecular biosynthetic pathways, and involvement in pain and nociception. Together, these findings advance our understanding of molecular lipidomic systems linking oxylipins and their precursors to nociceptive and inflammatory signaling pathways in rats. PERSPECTIVE We applied a systems approach to characterize molecular pathways linking precursor lipids and oxylipins to nociceptive signaling. This systematic, quantitative evaluation of the molecular pathways linking oxylipins to nociception provides a framework for future basic and clinical research investigating the role of oxylipins in pain.

Studies on serological responses following coronavirus disease-2019 (COVID-19) have been published primarily in individuals who are moderately or severely symptomatic, but there are few data from individuals who are mildly symptomatic or asymptomatic.

We measured IgG, IgM, and IgA to the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by using enzyme-linked immunosorbent assay in mildly symptomatic (n = 108) and asymptomatic (n = 63) on days 1, 7, 14, and 30 following RT-PCR confirmation in Bangladesh and when compared with pre-pandemic samples, including healthy controls (n = 73) and individuals infected with other viruses (n = 79).

Mildly symptomatic individuals developed IgM and IgA responses by day 14 in 72% and 83% of individuals, respectively, while 95% of individuals developed IgG response, and rose to 100% by day 30. In contrast, individuals infected with SARS-CoV-2 but who remained asymptomatic developed antibody responses significantly less frequently, with only 20% positive for IgA and 22% positive for IgM by day 14, and 45% positive for IgG by day 30 after infection.

These results confirm immune responses are generated following COVID-19 who develop mildly symptomatic illness. However, those with asymptomatic infection do not respond or have lower antibody levels. These results will impact modeling needed for determining herd immunity generated by natural infection or vaccination.

These results confirm immune responses are generated following COVID-19 who develop mildly symptomatic illness. However, those with asymptomatic infection do not respond or have lower antibody levels. These results will impact modeling needed for determining herd immunity generated by natural infection or vaccination.

Community-acquired (CAIs) and healthcare-associated (HAIs) infections are associated with significant morbidity and mortality. JHU-083 solubility dmso Data related to the epidemiology of these infections in the Middle East is scarce. The aim of this study is to estimate the prevalence of infections and antimicrobial use in the acute hospital setting in this region.

A multicentre Point-Prevalence Survey was conducted in seven Middle Eastern countries Egypt, Kingdom of Saudi Arabia, United Arab Emirates, Lebanon, Oman, Kuwait and Bahrain. Data were collected by the infection control and infectious diseases teams of the respective hospitals. Study surveys were completed in one day (03 April 2018).

The overall point prevalence of infection was 28.3%; HAI and CAI point prevalence was 11.2% and 16.8%, respectively. The majority of patients with an infection (98.2%) were receiving antimicrobial therapy. There were high levels of resistance to antimicrobials among Acinetobacter baumannii, Enterobacter cloacae, Klebsiella pneumoniae and other Klebsiella sp.