Rejected

The effect that the route of maternal fentanyl administration has on placental transfer of drug to the neonate is not well studied. Plasma concentration ratios are an indicator of fetal exposure, relative to the mother.

To analyse how the New Zealand news media has reported on chronic pain and identify whether this publicly available information is reflective of best practice.

Occipital nerve stimulation (ONS) and deep brain stimulation (DBS) are widely used surgical treatments for chronic refractory cluster headache (CH). However, there is little literature regarding long-term follow-up of these treatments.

Presentation We describe an unusual presentation of sigmoid colon perforation secondary to an ingested chicken bone. Diagnosis The patient presented with a 4 day history of abdominal pain and distension. On examination there were signs of peritonism. Inflammatory markers were raised. Computed tomography revealed a linear density projecting through the wall of the colon. Treatment The patient underwent emergency laparotomy and a Hartmann's procedure. A chicken bone was found to be the causative foreign object. Conclusion Foreign body ingestion is an uncommon cause of sigmoid perforation which may mimic more common surgical presentations such as diverticulitis.

To investigate the behaviours of elite and developing athletes in obtaining medications and medication information, and to identify the role of pharmacists in athlete care.

Recent discoveries demonstrate a critical role for circadian rhythms and sleep in immune system homeostasis. Both innate and adaptive immune responses – ranging from leukocyte mobilization, trafficking, and chemotaxis to cytokine release and T cell differentiation -are mediated in a time of day-dependent manner. The National Institutes of Health (NIH) recently sponsored an interdisciplinary workshop, "Sleep Insufficiency, Circadian Misalignment, and the Immune Response," to highlight new research linking sleep and circadian biology to immune function and to identify areas of high translational potential. This Review summarizes topics discussed and highlights immediate opportunities for delineating clinically relevant connections among biological rhythms, sleep, and immune regulation.

Extended-release local anesthetics (LAs) have drawn increasing attention with their promising role in improving analgesia and reducing adverse events of LAs. Nano-structured carriers such as liposomes and polymersomes optimally meet the demands of/for extended-release, and have been utilized in drug delivery over decades and showed satisfactory results with extended-release. Based on mature technology of liposomes, EXPAREL, the first approved liposomal LA loaded with bupivacaine, has seen its success in an extended-release form. At the same time, polymersomes has advances over liposomes with complementary profiles, which inspires the emergence of hybrid carriers. This article summarized the recent research successes on nano-structured extended-release LAs, of which liposomal and polymeric are mainstream systems. Furthermore, with continual optimization, drug delivery systems carry properties beyond simple transportation, such as specificity and responsiveness. In the near future, we may achieve targeted delivery and controlled-release properties to satisfy various analgesic requirements.

P63 is a major transcription factor regulating skin development and homeostasis. It controls many genes involved in cell proliferation, adhesion, and early differentiation. P63 is mutated in several rare syndromes called p63-related ectodermal dysplasia syndromes (ED). The main forms are EEC and AEC syndromes due to p63 missense mutations on the DBD and SAM domains, respectively. ED patients display many developmental defects, including ectrodactyly, clef/lip palate, and ectodermal dysplasia, while AEC patients suffer from severe skin erosions that not always heal. We have previously showed that ED-derived iPSC display altered epidermal commitment. P63 belongs to the p53 gene family sharing similar structural domains. We found that ED-iPSC epidermal commitment can be rescued by a p53-reactivating compounds called PRIMA-1, also named APR-246 and currently used in anticancer clinical trials. Here, we established primary epidermal culture from two AEC children (S.F. and Y.M.) suffering from persistent skin erosions at age of 9 and 15, respectively. These patients carry missense mutations on the SAM domain (I576T and I537T). We found that primary keratinocytes (KCs) isolated from these AEC patients underwent altered epidermal differentiation that was rescued by PRIMA-1 treatment. It prompted us to formulate the compound onto a cream that was topically applied on the right hand of one patient and on the scalp of the second patient. In both cases, the daily treatment allowed re-epithelialization of the eroded skin and a drastic loss of pain after few weeks, improving quality of life. Normally, mutant p63 exerts a dominant-negative effect, mainly through the formation of aggregate with WT p63 and p73. PRIMA-1 did not reduce protein aggregation while enhancing cell differentiation, suggesting that PRIMA-1 targets cell differentiation and not p63 activity directly. In conclusion, we propose that repurposing of the antitumoral PRIMA-1 compound could become a general treatment of AEC skin erosions.

This trial addresses the global problem of chronic venous leg ulcers (CVLUs), wounds that cause significant infirmity for an estimated 9.7 million people annually, mainly older adults with comorbidities. Advanced therapies are needed because standard topical therapies are often ineffective or yield only short-term wound healing. Thus, we are testing a new oral therapy containing the bioactive elements of fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for targeting and reducing the high numbers of activated polymorphonuclear leukocytes (PMN) in wound microenvironments that keep CVLUs "trapped" in a chronic inflammatory state.

This is a real-world evidence study that aims to analyze the efficacy, tolerability and safety profile of paritaprevir/ombitasvir/ritonavir and dasabuvir, in patients with renal impairment.