Anticancer Effects of the Novel Pyrazolyl-Urea GeGe-3.

In a screen of over 200 novel pyrazole compounds, ethyl 1-(2-hydroxypentyl)-5-(3-(3-(trifluoromethyl) phenyl)ureido)-1H-pyrazole-4-carboxylate (named GeGe-3) has emerged as a potential anticancer compound. GeGe-3 displays potent anti-angiogenic properties through the presumptive targeting of the protein kinase DMPK1 and the Ca2+-binding protein calreticulin. We further explored the anticancer potential of GeGe-3 on a range of established cancer cell lines, including PC3 (prostate adenocarcinoma), SKMEL-28 (cutaneous melanoma), SKOV-3 (ovarian adenocarcinoma), Hep-G2 (hepatocellular carcinoma), MDA-MB231, SKBR3, MCF7 (breast adenocarcinoma), A549 (lung carcinoma), and HeLa (cervix epithelioid carcinoma). At concentrations in the range of 10 µM, GeGe-3 significantly restricted cell proliferation and metabolism. GeGe-3 also reduced PC3 cell migration in a standard wound closure and trans-well assay. Together, these results confirm the anticancer potential of GeGe-3 and underline the need for more detailed pre-clinical investigations into its molecular targets and mechanisms of action.

Targeted temperature management in patients with intracerebral haemorrhage, subarachnoid haemorrhage, or acute ischaemic stroke: updated consensus guideline recommendations by the Neuroprotective Therapy Consensus Review (NTCR) group.

BACKGROUND: There is a lack of consistent, evidence-based guidelines for the management of patients with fever after brain injury. The aim was to update previously published consensus recommendations on targeted temperature management after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in patients who require admission to critical care. METHODS: A modified Delphi consensus, the Neuroprotective Therapy Consensus Review (NTCR), included 19 international neuro-intensive care experts with a subspecialty interest in the acute management of intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke. An online, anonymised survey was completed ahead of the meeting before the group came together to consolidate consensus and finalise recommendations on targeted temperature management. A threshold of ≥80% for consensus was set for all statements. RESULTS: Recommendations were formulated based on existing evidence, literature review, and consensus. After intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in patients who require critical care admission, core temperature should ideally be monitored continuously and maintained between 36.0°C and 37.5°C using automated feedback-controlled devices, where possible. Targeted temperature management should be commenced within 1 h of first fever identification with appropriate diagnosis and treatment of infection, maintained for as long as the brain remains at risk of secondary injury, and rewarming should be controlled. Shivering should be monitored and managed to limit risk of secondary injury. Following a single protocol for targeted temperature management across intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke is desirable. CONCLUSIONS: Based on a modified Delphi expert consensus process, these guidelines aim to improve the quality of targeted temperature management for patients after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in critical care, highlighting the need for further research to improve clinical guidelines in this setting.

Biological effects of polystyrene micro- and nano-plastics on human intestinal organoid-derived epithelial tissue models without and with M cells.

Micro- and nano-plastics (MPs and NPs) released from plastics in the environment can enter the food chain and target the human intestine. However, knowledge about the effects of these particles on the human intestine is still limited due to the lack of relevant human intestinal models to validate data obtained from animal studies or tissue models employing cancer cells. In this study, human intestinal organoids were used to develop epithelia to mimic the cell complexity and functions of native tissue. Microfold cells (M cells) were induced to distinguish their role when exposure to MPs and NPs. During the exposure, the M cells acted as sensors, capturers and transporters of larger sized particles. The epithelial cells internalized the particles in a size-, concentration-, and time-dependent manner. Importantly, high concentrations of particles significantly triggered the secretion of a panel of inflammatory cytokines linked to human inflammatory bowel disease (IBD).

Long-term support referrals to enhance food security and well-being in older adults: Texas physicians and nurses on what works.

Aim: Senior participation in the congregate meal programs (CMPs) has alarmingly declined over the past decade in Texas as elsewhere in the nation. The purpose of this survey study was to identify the possible reasons for this decline from the viewpoint of the Texas physicians and nurses who are key in coordinating care and ensuring food security for the vulnerable older Texans by referring them to community-based long-term support services (LTSS). Subject and methods: The methodology adopted was an online panel survey of physicians and nurses from rural and urban Texas counties. Structured multiple-choice and open-ended questions primarily focused on provider referral processes, reasons for connecting older clients to CMPs, perceptions about various aspects of these programs, possible reasons for the decline in participation, suggestions to make the programs an integral part of the community-based LTSS referral system, and how to address the COVID-19 pandemic constraints on the programs. Results: As a majority of the healthcare providers surveyed were unaware of the CMPs in their communities, the study spotlighted an urgent need for a better-coordinated referral process centered on strategic marketing and awareness-building about the CMPs, including an extensive healthcare provider education component as well as an overall improvement in meal quality and variety. Conclusion: The study highlights a need for additional research so decision-makers better understand how to best disseminate information to healthcare providers to improve the referral mechanisms, increase the referrals, and enhance the overall CMP program quality to benefit the vulnerable food-insecure older adults.

When can a professional athlete return to play following scapholunate ligament delayed reconstruction?

BACKGROUND: The aim of this study was to determine the outcomes in relation to return-to-play in professional athletes who had undergone a delayed scapholunate ligament reconstruction. METHODS: We searched our prospectively managed database and identified 15 professional athletes who had undergone the modified Brunelli procedure for scapholunate instability. They were contacted to complete a telephone interview. We established the duration between the operation and return-to-play, the level of competition before and after the procedure and if applicable, reasons for reduction in the level of competition. RESULTS: Between 2008 and 2011, 15 professional male athletes underwent the modified Brunelli procedure. One was lost to follow-up and 14 athletes (11 rugby, 2 boxing and 1 golf) were contactable. The mean age of the patients was 30 years (range 18-42). The mean follow-up period was 25 months (range 3-43). Eleven of the 14 (79%) athletes returned to play within 4 months of surgery. By the final review, 9 of the 14 (64%) athletes had returned to play at their preinjury level of competition. CONCLUSIONS: A majority (approximately 80%) of professional athletes return to competitive playing within 4 months of undergoing a scapholunate ligament reconstruction. Approximately two-thirds return to play at their preinjury level of competition.