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Obtaining patent protection for microbiome therapeutics has been affected profoundly by the US Supreme Court decisions in Myriad and Mayo, which redefined the scope of which natural phenomena, including microbiome therapeutics, are patent eligible. [ABSTRACT FROM AUTHOR]

Road trauma in India is a significant health and socio-economic burden which requires urgent attention. When compared to countries with established trauma systems, those injured in India have up to a six-fold higher mortality rate. The death rate would be reduced with better organized systems of trauma care. This is dependent on state authorities introducing systems that fund accident prevention along with the organized care of the injured. The goal of an effective trauma system should be to provide universal emergency care with equity of access. The belief that trauma care cannot be cost-effective in low-income settings needs to be refuted. Better planning will result in cost-effective improvements in patient outcomes. However, without protected and guaranteed funding schemes, the development of trauma systems in India will fail. [ABSTRACT FROM AUTHOR]

dMax, a naturally occurring splice variant of the Myc binding protein Max, lacks the DNA binding basic region and helix 1 of the Helix – Loop – Helix domain; dMax interacts with c-Myc in vitro and in vivo, and inhibits E-box Myc site driven transcription in transient transfection assays. Here we have investigated the expression, function and interactions of dMax. RT/PCR analyses detected dmax mRNA in multiple tissues of the developing, newborn and adult mouse. Functionally, dMax reduced the ability of c-Myc to cooperate with the progression factor A-Myb to promote S phase entry of quiescent smooth muscle cells. In contrast, dMax failed to ablate inhibition of initiator element (Inr)-mediated transcription by c-Myc in Jurkat T cells. In in vitro protein : protein association assays, dMax interacted with c-Myc, N-Myc, L-Myc, Mad1, Mxi1, Mad3 and Mad4, but not with itself or wild-type Max. These interactions required an intact leucine zipper. Inhibition of E-box-mediated transactivation by induction of dMax overexpression resulted in apoptosis of WEHI 231 B cells. Thus, dMax is a widely expressed, naturally occurring protein, with the capacity to bind most members of the Myc/Max superfamily; dMax has little effect on Inr-mediated repression by c-Myc, but can significantly decrease E-box-mediated events promoting proliferation and cell survival. [ABSTRACT FROM AUTHOR]

Upon engagement of the B Cell Receptor (BCR) of WEHI 231 immature B cells, a drop in c-Myc expression is followed by activation of the cyclin-dependent kinase inhibitor (CKI) p27Kip1, which induces growth arrest and apoptosis. Here, we report inverse patterns of p27 and c-Myc protein expression follow BCR engagement. We present evidence demonstrating, for the first time, that the p27Kip1 gene is a target of transcriptional repression by c-Myc. Specifically, the changes in p27 protein levels correlated with changes in p27 mRNA levels, and gene transcription. Induction of p27 promoter activity followed BCR engagement of WEHI 231 cells, and this induction could be repressed upon co-transfection of a c-Myc expression vector. Inhibition of the TATA-less p27 promoter by c-Myc was also observed in Jurkat T cells, vascular smooth muscle, and Hs578T breast cancer cells, extending the observation beyond immune cells. Consistent with a putative Inr element CCAGACC (where +1 is underlined) at the start site of transcription in the p27 promoter, deletion of Myc homology box II reduced the extent of repression. Furthermore, enhanced repression was observed upon transfection of the c-Myc ‘super-repressor’, with mutation of Phe115 to Leu. The sequences mediating transcriptional activity and c-Myc repression were mapped to bp -20 to +20 of the p27 gene. Finally, binding of Max was shown to facilitate c-Myc binding and repression of p27 promoter activity. Overall, these studies identify the p27 CKI gene as a new target whereby c-Myc can control cell proliferation, survival and neoplastic transformation. Oncogene (2001) 20, 1688–1702. [ABSTRACT FROM AUTHOR]

Blunt vertebral artery injury (VAI) is associated with severe cervicocephalic trauma and may have devastating consequences. This study aimed to determine the incidence and nature of VAI in polytrauma patients. The secondary objective was to assess the association of VAI with previously suggested risk factors. It was a retrospective observational study of all polytrauma patients admitted to the trauma unit between April 2018 and July 2019, who had CT neck angiography to diagnose blunt VAI according to modified Denver criteria. Out of 1084 admitted polytrauma patients, 1025 (94.6%) sustained blunt trauma. Of these, 120 (11.7%) underwent screening CT neck angiography. VAI was detected in 10 (8.3%; 95% CI 4.1–14.8) patients. There were three patients with Grade I injury, two with Grade II, and five with Grade IV injury. Among all trauma admissions, the incidence of diagnosed VAI was 0.9% (95% CI 0.5–1.8). Among patients suspected of VAI, there was no univariable association of VAI with C-Spine fracture: OR 4.2 (95% CI 0.51–34.4; p = 0.18). There were two (20%) deaths related to VAI. Traumatic VAI was uncommonly detected in this major trauma service in Saudi Arabia. High suspicion and liberal screening by CT angiography in cases where VAI is possible should be considered to avoid missed injuries. [ABSTRACT FROM AUTHOR]

Background: Multiple screening Duplex ultrasound scans (DUS) are performed in trauma patients at high risk of deep vein thrombosis (DVT) in the intensive care unit (ICU). Intensive care physician performed compression ultrasound (IP-CUS) has shown promise as a diagnostic test for DVT in a non-trauma setting. Whether IP-CUS can be used as a screening test in trauma patients is unknown. Our study aimed to assess the agreement between IP-CUS and vascular sonographer performed DUS for proximal lower extremity deep vein thrombosis (PLEDVT) screening in high-risk trauma patients in ICU. Methods: A prospective observational study was conducted at the ICU of Alfred Hospital, a major trauma center in Melbourne, Australia, between Feb and Nov 2015. All adult major trauma patients admitted with high risk for DVT were eligible for inclusion. IP-CUS was performed immediately before or after DUS for PLEDVT screening. The paired studies were repeated twice weekly until the DVT diagnosis, death or ICU discharge. Written informed consent from the patient, or person responsible, or procedural authorisation, was obtained. The individuals performing the scans were blinded to the others' results. The agreement analysis was performed using Cohen's Kappa statistics and intraclass correlation coefficient for repeated binary measurements. Results: During the study period, 117 patients had 193 pairs of scans, and 45 (39%) patients had more than one pair of scans. The median age (IQR) was 47 (28–68) years with 77% males, mean (SD) injury severity score 27.5 (9.53), and a median (IQR) ICU length of stay 7 (3.2–11.6) days. There were 16 cases (13.6%) of PLEDVT with an incidence rate of 2.6 (1.6–4.2) cases per 100 patient-days in ICU. The overall agreement was 96.7% (95% CI 94.15–99.33). The Cohen's Kappa between the IP-CUS and DUS was 0.77 (95% CI 0.59–0.95), and the intraclass correlation coefficient for repeated binary measures was 0.75 (95% CI 0.67–0.81). Conclusions: There is a substantial agreement between IP-CUS and DUS for PLEDVT screening in trauma patients in ICU with high risk for DVT. Large multicentre studies are needed to confirm this finding. [ABSTRACT FROM AUTHOR]