Strengthening Molecular Glues: Design Strategies for Improving Thalidomide Analogs as Cereblon Effectors and Anticancer Agents.

In the two decades since a novel thalidomide analog was last approved, many promising drug candidates have emerged with remarkable potency as targeted protein degraders. Likewise, the advent of PROTACs for suppressing 'undruggable' protein targets reinforces the need for new analogs with improved cereblon affinity, target selectivity and drug-like properties. However, thalidomide and its approved derivatives remain plagued by several shortcomings, such as structural instability and poor solubility.

Dirhodium-Catalyzed Transannulation of -Sulfonyl-1,2,3-triazoles to 2,3-Dehydropiperazines.

The dirhodium(II)-catalyzed synthesis of a range of C2-substituted 2,3-dehydropiperazines using 1-mesyl-1,2,3-triazoles and β-haloalkylcarbamates is reported. The reaction is proposed to proceed through an α-imino rhodium carbene 1,3-insertion into N-H followed by a base-mediated cyclization. C-Substituted dehydropiperazines can also be conducted directly from terminal alkynes in a three-step, one-pot operation, forming the triazole .

Lessons learnt from the first 200 unselected consecutive cases of laparoscopic exploration of common bile duct stones at a district general hospital.

Background: The management of choledocholithiasis evolves with diagnostic imaging and therapeutic technology, facilitating a laparoscopic approach. We review our first 200 cases of laparoscopic exploration of the common bile duct, highlighting challenges and lessons learnt.

Methods: We retrospectively studied the first 200 cases of laparoscopic cholecystectomy with common bile duct exploration between 2006 and 2019.

A One-Pot Reaction of α-Imino Rhodium Carbenoids and Halohydrins: Access to 2,6-Substituted Dihydro-2-1,4-oxazines.

Herein, we report a Rh(II)-catalyzed reaction between 1-tosyl-1,2,3-triazoles and halohydrins to provide 2,6-substituted 3,4-dihydro-2-1,4-oxazines under basic conditions. The reaction is proposed to undergo a rhodium carbenoid 1,3-insertion into O-H followed by an annulation. The scope includes phenyl or alkenyl C4-substituted triazoles and a range of halohydrins using catalytic RhOct and KCO.

Ileus and small bowel obstruction after radical cystectomy for bladder cancer: Analysis from the Nationwide Inpatient Sample.

Purpose: To investigate prevalence and predictors of postoperative small bowel obstruction (SBO) and ileus in a large cohort of bladder cancer (BCa) patients treated with radical cystectomy (RC).

Methods: All patients within the Nationwide Inpatient Sample who underwent RC for BCa between 2006 and 2012 were identified. First, prevalence of SBO and ileus was analyzed.

Ejaculatory dysfunction in the treatment of lower urinary tract symptoms.

The link between lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) and sexual dysfunction is well established. Sexual dysfunction can encompass both ejaculatory dysfunction (EjD) and erectile dysfunction (ED). Ejaculatory dysfunction can consist of premature ejaculation, delayed ejaculation, retrograde ejaculation, anejaculation, decreased force of ejaculation and pain upon ejaculation.

Vasectomy and prostate cancer risk: a historical synopsis of undulating false causality.

The potential influence of vasectomy being a risk factor for the development of prostate cancer is not a new concept, with more than 30 publications addressing the topic. Given the global frequency of vasectomy and the prevalence of prostate cancer, this subject justifiably deserves scrutiny. Several articles have claimed that vasectomy puts men at risk for future development of prostate cancer.

Impact of Urologist Density and County Rurality on the Practice of Retroperitoneal Lymph Node Dissection and Cancer-Specific Death in Patients with Nonseminomatous Germ Cell Tumors.

Purpose: To investigate the impact of rural status and urologist density on the practice of retroperitoneal lymph node dissection (RPLND) and cancer-specific death (CSD) in patients with nonseminomatous germ cell tumor (NSGCT).

Methods: Urologist density was determined from 2014 to 2015 Area Health Resource File data, and rural residence was determined using the 2003 Rural-Urban Continuum Codes. All cases of NSGCT within Surveillance, Epidemiology and End Results (SEER) 18 with known county code were used for analysis (n = 9473).

Derivation of a Provisional, Age-dependent, AIS2+ Thoracic Risk Curve for the THOR50 Test Dummy via Integration of NASS Cases, PMHS Tests, and Simulation Data.

A provisional, age-dependent thoracic risk equation (or, "risk curve") was derived to estimate moderate-to-fatal injury potential (AIS2+), pertaining to men with responses gaged by the advanced mid-sized male test dummy (THOR50). The derivation involved two distinct data sources: cases from real-world crashes (e.g.

Contemporary Incidence and Mortality Rates of Neuroendocrine Prostate Cancer.

Aim: The purpose of the study was to provide an update ever the incidence and mortality for neuroendocrine prostate cancer (NEPC) in the United States.

Patients And Methods: Using a large national database, we examined changes in age-adjusted incidence (AAIR), mortality rates (MR) and 5-year cancer-specific survival (CSS) for 378 patients diagnosed with NEPC between 1992 and 2011. Analysis was performed for all NEPC and for its two major sub-groups [small cell carcinoma (SCC) and neuroendocrine carcinoma (NEC)].

Partial nephrectomy for T2 renal masses: contemporary trends and oncologic efficacy.

Purpose: Increasing popularity and improved technical feasibility of partial nephrectomy (PN) has encouraged urologists to treat larger renal masses with nephron-sparing surgery. We used a national database to characterize practice patterns for the surgical management of patients with T2 renal tumors and examined the effect of PN on cancer-specific survival in such patients.

Methods: Between 2001 and 2011, 10,259 patients with primary tumor size >7 cm confined to the kidney (T2) were treated surgically for kidney cancer.

Are intra-gastric adjustable balloon system safe? A case series.

Introduction: Intra-gastric balloons have been in use as an aide to weight loss. Since its introduction, it has evolved from air filled to saline filled intra-gastric balloons. The SPATZ-ABS is a new adjustable saline filled balloon.

Congenital diaphragmatic hernia: an unusual cause of obstructive jaundice.

Congenital diaphragmatic hernias in adults are exceedingly rare. They have been reported to cause dyspnoea, gastric reflux and intestinal obstruction. We present the case of a young woman with obstructive jaundice secondary to a Bochdalek hernia of the right hemidiaphragm.

Congenital band of the vitelline artery remnant as a cause of chronic lower abdominal pain in an adult: Case report.

Introduction: Intraabdominal bands of the vitelline vessel remnant are the rarest form of congenital mesodiverticluar bands which may or may not be associated with Meckel's diverticulum. In the majority of cases they cause an acute abdominal disease such as intestinal obstruction, especially in children.

Presentation Of Case: We report a case of a 64 year old gentleman who experienced recurrent episodes of abdominal distension and bloating over two years.

Nurse care coordinators: definitions and scope of practice.

The Nurse Care Coordinator role has emerged in recent years as an important means of achieving significant outcomes for patient, their families, and the larger health system. These outcomes include increased patient satisfaction with service provision, an increase in patient access to services, and a decrease in the hospital length of stay and unplanned readmission. Despite the potential benefits, confusion around role definition and scope of practice are evident.

Considerations of "Combined Probability of Injury" in the next-generation USA frontal NCAP.

Objective: The numerical basis for assigning star ratings in the next-generation USA New Car Assessment Program (NCAP) for frontal impacts was assessed. That basis, the Combined Probability of Injury, or CPI, is the probability of an occupant sustaining an injury to any of the specified body regions. For an NCAP test, a CPI value is computed by (a) using risk curves to convert body-region responses from a test dummy into body-region risks and (b) using a theoretical, overarching CPI equation to convert those separate body-region risks into a single CPI value.

Duodenal polypectomy is a rare cause of acute pancreatitis.

Endoscopic duodenal polypectomy is a routine procedure particularly useful for obtaining histological diagnosis but it is not without serious complications. This is a case report of severe necrotising pancreatitis after duodenal polypectomy. We suggest that experienced endoscopists should carry out polypectomies and that clear guidelines for the management of duodenal polyps are required.

A calcified lung tumour and microcytic anaemia in a young woman: partial expression of the Carney triad.

The Carney triad is the non-familial addociation of gastric stromal tumours (GISTs), pulmonar chondromas and extra-adrenal paragangliomas. Fewer than 100 cases of the disorder have been reported since its description in 1977. The condition has a predeliction for young women.

Designing Pd-on-Au bimetallic nanoparticle catalysts for trichloroethene hydrodechlorination.

Alumina-supported palladium (Pd) catalysts have previously been shown to hydrodechlorinate trichloroethene (TCE) and other chlorinated compounds in water, at room temperature, and in the presence of hydrogen. The feasibility of this catalytic technology to remediate groundwater of halogenated compounds can be improved by re-designing the Pd material in order to increase catalytic activity. We synthesized and characterized Pd supported on gold nanoparticles (Au NPs) of different Pd loadings.

Heat shock protein and high-dose aspirin: effects on random skin flap survival in a rat model.

The heat shock response is known to have a protective effect against flap ischemia. It has been shown that heat shock protein (hsp) expression can be augmented in vivo with the administration of high-dose aspirin before heat treatment. The authors hypothesized that administration of aspirin before hsp induction through heat stress would enhance further the protective effects of the heat shock response against skin flap ischemia.

Macrophage depletion alters vein graft intimal hyperplasia.

Background: The principal cause of vein graft failure is intimal hyperplasia (IH); however, its etiology remains unclear. In a rat model of vein graft IH we have observed prolonged transmural macrophage infiltration, leading us to hypothesize that these cells regulate IH. To test this, we used liposome-encapsulated dichloromethylene bisphosphonate (L-Cl2MBP) to deplete rat macrophages and observed the effects on IH.

Assessment of function, perfusion, metabolism, and histology in hearts preserved with University of Wisconsin solution.

Background: University of Wisconsin solution has shown promise for prolonged cardiac preservation. This study compared the effects of 24-hour cold storage and perfusion preservation techniques by assessment of function, perfusion, metabolism, and histological changes.

Methods And Results: Three groups of rabbit hearts (n = 6 each) were evaluated: 1) control with immediate reperfusion, 2) continuous perfusion preservation, and 3) cold storage.

Effects of oxygenated cardioplegic solutions on myocardial aerobic metabolism.

Oxygenated cardioplegic solutions can deliver sufficient oxygen to support aerobic metabolism of heart tissue during cardiac arrest, but little is known about oxygen use after cardioplegic solution infusion. Exhaustion of myocardial oxygen stores after infusion of oxygenated crystalloid cardioplegic solution or Krebs-Henseleit buffer was measured in rat hearts. Since nicotinamide adenine dinucleotide accumulates when mitochondria become anaerobic, the epicardium was monitored during perfusion and ischemia.