Sex-Specific Effects of Buprenorphine on Endoplasmic Reticulum Stress, Abnormal Protein Accumulation, and Cell Loss After Pediatric Mild Traumatic Brain Injury in Mice.

Traumatic brain injury (TBI) in children often leads to poor developmental outcomes attributable to progressive cell loss caused by secondary injuries, including endoplasmic reticulum (ER) stress. Buprenorphine (BPN) is commonly used in children for pain management; however, the effects of BPN on ER stress in the pediatric population are still inconclusive. This study investigated the sex-specific effects of BPN on ER stress, abnormal protein accumulation, and cell loss in a mouse impact acceleration model of pediatric TBI. On post-natal day 20-21 (P20-21), male and female littermates were randomized into sham, TBI + saline and TBI + BPN groups. BPN (0.075 mg/kg) was administered to TBI + BPN mice at 30 min after injury and then every 6-12 h for 2 days. The impact of BPN was evaluated at 1, 3, and 7 days post-injury. We found that TBI induced more prominent ER stress pathway activation at 1 and 3 days post-injury in males, compared to females, whereas abnormal protein accumulation and cell loss were more severe in females at 7 days post-injury, compared with males. Although BPN partially ameliorated abnormal protein accumulation and cell loss in both males and females, BPN only decreased ER stress pathway activation in males, not in females. In conclusion, BPN exhibits sex-specific effects on ER stress, abnormal protein accumulation, and cell loss in a time-dependent manner at the acute phase after pediatric TBI, which provides the rationale to assess the potential effects of BPN on long-term outcomes after pediatric TBI in both males and females.

Impact of pediatric traumatic brain injury on hippocampal neurogenesis.

Traumatic brain injury (TBI) is a major cause of mortality and morbidity in the pediatric population. With advances in medical care, the mortality rate of pediatric TBI has declined. However, more children and adolescents are living with TBI-related cognitive and emotional impairments, which negatively affects the quality of their life. Adult hippocampal neurogenesis plays an important role in cognition and mood regulation. Alterations in adult hippocampal neurogenesis are associated with a variety of neurological and neurodegenerative diseases, including TBI. Promoting endogenous hippocampal neurogenesis after TBI merits significant attention. However, TBI affects the function of neural stem/progenitor cells in the dentate gyrus of hippocampus, which results in aberrant migration and impaired dendrite development of adult-born neurons. Therefore, a better understanding of adult hippocampal neurogenesis after TBI can facilitate a more successful neuro-restoration of damage in immature brains. Secondary injuries, such as neuroinflammation and oxidative stress, exert a significant impact on hippocampal neurogenesis. Currently, a variety of therapeutic approaches have been proposed for ameliorating secondary TBI injuries. In this review, we discuss the uniqueness of pediatric TBI, adult hippocampal neurogenesis after pediatric TBI, and current efforts that promote neuroprotection to the developing brains, which can be leveraged to facilitate neuroregeneration.

COVID-19 and the Global Impact on Colorectal Practice and Surgery.

BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 virus that emerged in December 2019 causing coronavirus disease 2019 (COVID-19) has led to the sudden national reorganization of health care systems and changes in the delivery of health care globally. The purpose of our study was to use a survey to assess the global effects of COVID-19 on colorectal practice and surgery. MATERIALS AND METHODS: A panel of International Society of University Colon and Rectal Surgeons (ISUCRS) selected 22 questions, which were included in the questionnaire. The questionnaire was distributed electronically to ISUCRS fellows and other surgeons included in the ISUCRS database and was advertised on social media sites. The questionnaire remained open from April 16 to 28, 2020. RESULTS: A total of 287 surgeons completed the survey. Of the 287 respondents, 90% were colorectal specialists or general surgeons with an interest in colorectal disease. COVID-19 had affected the practice of 96% of the surgeons, and 52% were now using telemedicine. Also, 66% reported that elective colorectal cancer surgery could proceed but with perioperative precautions. Of the 287 respondents, 19.5% reported that the use of personal protective equipment was the most important perioperative precaution. However, personal protective equipment was only provided by 9.1% of hospitals. In addition, 64% of surgeons were offering minimally invasive surgery. However, 44% reported that enough information was not available regarding the safety of the loss of intra-abdominal carbon dioxide gas during the COVID-19 pandemic. Finally, 61% of the surgeons were prepared to defer elective colorectal cancer surgery, with 29% willing to defer for ≤ 8 weeks. CONCLUSION: The results from our survey have demonstrated that, globally, COVID-19 has affected the ability of colorectal surgeons to offer care to their patients. We have also discussed suggestions for various practical adaptation strategies for use during the recovery period.

A prospective diagnostic study on povidone-iodine retention in lesions suspected to be squamous cell carcinoma or keratoacanthoma.

BACKGROUND AND OBJECTIVES: While dermatoscopy improves diagnostic accuracy for raised nonpigmented lesions, those with white surface keratin can be problematical. We investigated whether retention of povidone-iodine by surface keratin provides a clue to benignity. METHODS: We performed a retrospective pilot study (n = 57) followed by a prospective study (n = 117) on raised nonpigmented lesions with white surface keratin. An initial dermatoscopic image was taken of each lesion, povidone-iodine was applied and another image taken. Following lavage with 70% ethanol, a third image was acquired. The percentage surface area of residual povidone-iodine staining after lavage was recorded, and the results analysed. RESULTS: The optimal cut-off point of residual staining was 80%, where values of ≤80% pointed to malignancy. At this cut-off, the OR for lesions with values ≤80% to be truly malignant in the retrospective set was 4.03 (95% CI: 2.1-7.6) and the AUC was 0.7 (95% CI: 0.62-0.78). For the prospective set, the corresponding OR was 2.3 (95% CI: 1.4-3.7) and the AUC was 0.62 (95% CI: 0.55-0.68). CONCLUSIONS: This study presents evidence that povidone-iodine retention may have a degree of efficacy in distinguishing benign from malignant keratotic lesions. Further study is warranted.

Systematic derivation of an Australian standard for Tall Man lettering to distinguish similar drug names.

RATIONALE, AIMS AND OBJECTIVES: Confusion between similar drug names can cause harmful medication errors. Similar drug names can be visually differentiated using a typographical technique known as Tall Man lettering. While international conventions exist to derive Tall Man representation for drug names, there has been no national standard developed in Australia. This paper describes the derivation of a risk-based, standardized approach for use of Tall Man lettering in Australia, and known as National Tall Man Lettering. METHOD: A three-stage approach was applied. An Australian list of similar drug names was systematically compiled from the literature and clinical error reports. Secondly, drug name pairs were prioritized using a risk matrix based on the likelihood of name confusion (a four-component score) vs. consensus ratings of the potential severity of the confusion by 31 expert reviewers. The mid-type Tall Man convention was then applied to derive the typography for the highest priority drug pair names. RESULTS: Of 250 pairs of confusable Australian drug names, comprising 341 discrete names, 35 pairs were identified by the matrix as an 'extreme' risk if confused. The mid-type Tall Man convention was successfully applied to the majority of the prioritized drugs; some adaption of the convention was required. CONCLUSION: This systematic process for identification of confusable drug names and associated risk, followed by application of a convention for Tall Man lettering, has produced a standard now endorsed for use in clinical settings in Australia. Periodic updating is recommended to accommodate new drug names and error reports.

Look-alike and sound-alike medicines: risks and 'solutions'.

'Look-alike, sound-alike' medicines are associated with dispensing errors. This commentary aims to fuel discussion surrounding how drug name nomenclature and similar packaging between medicines can lead to selection errors, the need for enhanced approval systems for medicine names and packaging, and best practice 'solutions'. The literature reveals a number of environmental risks and human factors that can contribute to such errors. To contextualise these risks, we interviewed 13 quality and safety experts, psycholinguists, and hospital and community pharmacy practitioners in Australia, and commissioned a medical software industry expert to conceptualise electronic initiatives. Environmental factors contributing to such errors, identified through both the literature and interviews, include distractions during dispensing; workflow controls should minimise the 'human factors' element of errors. Technological solutions with some support, and yet recognised limitations, include font variations, automated alerts, barcode scanning and real-time reporting programmed into dispensing software; further development of these initiatives is recommended.