Rocaglates induce gain-of-function alterations to eIF4A and eIF4F

Rocaglates are a diverse family of biologically active molecules that have gained tremendous interest in recent years due to their promising activities in pre-clinical cancer studies. As a result, this family of compounds has been significantly expanded through the development of efficient synthetic schemes. However, it is unknown whether all of the members of the rocaglate family act through similar mechanisms of action. Here, we present a comprehensive study comparing the biological activities of >200 rocaglates to better understand how the presence of different chemical entities influences their biological activities. Through this, we find that most rocaglates preferentially repress the translation of mRNAs containing purine-rich 5' leaders, but certain rocaglates lack this bias in translation repression. We also uncover an aspect of rocaglate mechanism of action in which the pool of translationally active eIF4F is diminished due to the sequestration of the complex onto RNA.P50 GM067041 - NIGMS NIH HHS; R24 GM111625 - NIGMS NIH HHS; R35 GM118173 - NIGMS NIH HHSPublished versio

The effects of adding local infiltration analgesia of the knee to a multimodal pain protocol for total arthroplasty: A matched pair retrospective study

Background: We hypothesize that the addition of local infiltration analgesia (LIA) to a multimodal pain protocol will reduce the total amount of opioids consumed for acute pain control post total knee arthrolplasty (TKA). Methods: This study was a retrospective, matched pair study including patients who had primary TKA. All patients included in the analysis had preoperative oral celecoxib and acetaminophen, had single-dose spinal anesthetic with intrathecal morphine, and had intravenous patient-controlled analgesia with an opioid agent in addition to gabapentin and celecoxib in the first 48 h. Patients whose charts were excluded from the study had revision TKA, received opioid therapy prior to the surgery, were classified as American Society of Anesthesiology (ASA) IV, and had general anesthesia. Fifty patients who underwent TKA and had LIA were matched for age, body mass index (BMI), and gender with patients who did not receive LIA. The primary outcome measures were total doses of opioids consumed post TKA. Results: Patients receiving LIA consumed on average significantly less intravenous (IV) morphine equivalents than patients not receiving LIA, with a mean difference (±SD) of 88.9 ± 15.6 mg IV morphine equivalents. Furthermore, pain control was better in the LIA group. The incidences of nausea and vomiting, pruritis, and excessive sedation were higher in the non-LIA group compared to the LIA group. There was no difference in the hospital length of stay between both groups. Conclusions: The addition of LIA to our multimodal pain protocol for TKA was associated with a reduction in total opioid consumption

sj-docx-1-sel-10.1177_17585732221142610 - Supplemental material for Surgical treatment options for articular cartilage defects of the glenohumeral joint: A systematic review

Supplemental material, sj-docx-1-sel-10.1177_17585732221142610 for Surgical treatment options for articular cartilage defects of the glenohumeral joint: A systematic review by Danielle Dagher, Asher Selznick, Carlos Prada, Yasser Al Shehab, Timothy Leroux and Moin Khan in Shoulder & Elbow</p

Rocaglates induce gain-of-function alterations to eIF4A and eIF4F

Rocaglates are a diverse family of biologically active molecules that have gained tremendous interest in recent years due to their promising activities in pre-clinical cancer studies. As a result, this family of compounds has been significantly expanded through the development of efficient synthetic schemes. However, it is unknown whether all of the members of the rocaglate family act through similar mechanisms of action. Here, we present a comprehensive study comparing the biological activities of >200 rocaglates to better understand how the presence of different chemical entities influences their biological activities. Through this, we find that most rocaglates preferentially repress the translation of mRNAs containing purine-rich 5′ leaders, but certain rocaglates lack this bias in translation repression. We also uncover an aspect of rocaglate mechanism of action in which the pool of translationally active eIF4F is diminished due to the sequestration of the complex onto RNA

The World Bank's Early Reflections on Development: A Development Institution or a Bank?

Until the late 1960s, the World Bank presented itself as an institution devoted to making sound and directly productive project loans. Yet, during its early years, discussions took place within the Bank regarding the possibility of issuing different types of loans, namely (i) loans aimed at tackling social issues ('social loans'), and (ii) loans aimed at providing foreign currency to address disequilibria in the balance of payments ('impact loans'). This paper brings together historical analysis and theories of organization development to study the housing issue as a case in point. The analysis reveals that the Bank was unwilling to lend for housing programmes not because these were not sound - in fact, they were - but because they were geared toward achieving social welfare objectives and were not directly linked to productive investment projects, such as dams, power stations, and railroads. This early decision had a significant impact on the subsequent development of the Bank's view of policy-making: it locked the institution into a particular lending pattern, and deprived it of important intellectual resources. It was not until the late 1960s that the Bank began to take social issues into consideration, rather late compared with other multilateral institutions.