Identifying Gender Barriers for Colorectal Cancer Screening and Assessing the Need for a Multigender Endoscopy Team: A Prospective Multicenter Study.

INTRODUCTION: Gender preferences have been reported as a barrier to colorectal cancer screening, particularly among women. We aim to identify the role of patients' gender preferences for endoscopists and endoscopy team members, with the effect of age-related and regional differences. METHODS: We conducted an anonymous, voluntary survey of all adult outpatients presenting at our endoscopy centers before their procedures. RESULTS: We received 2,138 (1,207 women, 905 men, and 26 undisclosed; 50% urban and 50% rural) completed surveys. The majority of the patients (89%) did not have an endoscopist gender preference, while 8% preferred a same-gender endoscopist, and 2% preferred an opposite gender endoscopist. Among patients who expressed a gender preference, men more commonly preferred a same-gender endoscopist than women (91% vs 67%, P < 0.05). More patients preferred a same-gender endoscopy team member than a same-gender endoscopist (17% vs 8%, P < 0.05), and women more commonly preferred a same-gender endoscopy team member than men (26% vs 6%, P < 0.05). Most patients who expressed same-gender endoscopist preference were between the ages of 50-69 years as compared to other age groups (P < 0.05). Of the urban patients, 9% expressed a same-gender endoscopist preference and 3% expressed an opposite gender preference, compared with 7% and 2% of rural patients (P < 0.05). Among patients with any endoscopist gender preference, rural patients were more willing to wait longer (41% vs 21%, P < 0.05), whereas urban patients were willing to pay more (64% vs 14%, P < 0.05) to have their preferences met. DISCUSSION: Contrary to previous studies, most patients did not have an endoscopist gender preference. Interestingly, men had more same-gender endoscopist preference, whereas women had more same-gender endoscopy team member preference. Age-related and regional differences exist among patients' gender preferences for their endoscopist and endoscopy team member, and addressing these preferences while creating an environment of a multigender endoscopy team may be beneficial in improving colorectal cancer screening.

Safety and Efficacy of Nitazoxanide-Based Regimen for the Eradication of Helicobacter pylori Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: Helicobacter pylori (HP) is the most common cause of gastritis worldwide. Clarithromycin-based triple therapy or bismuth-based quadruple therapy is usually considered the first-line treatment, however with around 30% failure rate for both regimens. Drug resistance of clarithromycin and metronidazole is a growing concern in some parts of the world. Therefore, there is a need for effective eradication regimen for HP. Nitazoxanide, a bactericidal thiazolide antibiotic, has been shown to be effective in HP infection. We conducted a systematic review and meta-analysis to evaluate the efficacy of nitazoxanide-based regimen for the eradication of HP. METHODS: We have searched PubMed, Embase, Ovid Medline and Cochrane library database from inception to December 9, 2020 to identify studies that utilized nitazoxanide in the treatment regimen for HP eradication. Our primary outcome was pooled eradication rate of HP. RESULTS: Thirteen studies including 1,028 patients met our inclusion criteria and were analyzed in a meta-analysis. HP eradication was successful in 867 patients with a pooled eradication rate of 86% (95% confidence interval (CI): 79-90%) with 84% heterogeneity. A subgroup analysis that included 230 patients who failed other prior eradication regimens revealed a pooled eradication rate of 85% (95% CI: 69-94%) without heterogeneity. In a subgroup analysis, highest eradication rates were achieved with levofloxacin, doxycycline, nitazoxanide and proton pump inhibitor with a pooled eradication rate of 92% (88-95%). CONCLUSION: Nitazoxanide-based regimen is safe and effective in the eradication of HP infection. It is also successful as a salvage therapy in patients who have failed prior treatments.

Autophagy in tumor suppression and cancer therapy.

Autophagy is a stress-induced cell survival program whereby cells under metabolic, proteotoxic, or other stress remove dysfunctional organelles and/or misfolded/polyubiquitylated proteins by shuttling them via specialized structures called autophagosomes to the lysosome for degradation. The end result is the release of free amino acids and metabolites for use in cell survival. For tumor cells, autophagy is a double-edged sword: autophagy genes are frequently mono-allelically deleted, silenced, or mutated in human tumors, resulting in an environment of increased oxidative stress that is conducive to DNA damage, genomic instability, and tumor progression. As such, autophagy is tumor suppressive. In contrast, it is important to note that although tumor cells have reduced levels of autophagy, they do not eliminate this pathway completely. Furthermore, the exposure of tumor cells to an environment of increased metabolic and other stresses renders them reliant on basal autophagy for survival. Therefore, autophagy inhibition is an active avenue for the identification of novel anti-cancer therapies. Not surprisingly, the field of autophagy and cancer has experienced an explosion of research in the past 10 years. This review covers the basic mechanisms of autophagy, discusses its role in tumor suppression and cancer therapy, and posits emerging questions for the future.

Parathyroid hormone stimulation of noncanonical Wnt signaling in bone.

In bone, parathyroid hormone (PTH) exerts either a catabolic or an anabolic effect depending on its method of administration. This paradoxical action has led to the use of PTH as an effective treatment for osteoporosis. The Wnt family of signaling proteins has a critical role in multiple events, which are necessary for proper animal development and survival, yet their exact method of action in bone remains elusive. We have uncovered a novel link between Wnt-4 and PTH. We think that, in bone, Wnt-4 signaling in response to PTH implicates cross-talk of multiple signaling pathways. This work hopes to further elucidate Wnt signaling in bone and provide greater understanding of PTH's anabolic effects in bone.

Determination of dual effects of parathyroid hormone on skeletal gene expression in vivo by microarray and network analysis.

Parathyroid hormone (PTH) stimulates bone formation when injected daily but causes severe bone loss with continuous infusion. The mechanism of its paradoxical effects is still elusive. In this study, we compared changes in the gene expression profile in bone induced by intermittent or continuous treatment with three different PTH peptides, PTH-(1-34), -(1-31), and -(3-34), in Sprague-Dawley female rats. PTH-(1-34) regulated numerous genes (approximately 1,000), but differentially, in both regimes. PTH-(1-31) regulated a similar number of genes in the intermittent regimen but fewer in the continuous regimen, consistent with its less potent catabolic effect. PTH-(3-34) regulated very few genes in both regimes, which suggests the protein kinase C pathway plays a limited role in mediating the dual effects of PTH, whereas the cAMP-dependent protein kinase A pathway appears to predominate. In the intermittent treatment, many genes encoding signaling mediators, transcription factors, cytokines, and proteases/protease inhibitors are regulated rapidly and cyclically with each PTH injection; genes associated with skeletal development show a slowly accruing pattern of expression. With continuous treatment, some genes are regulated from 6 h, and the mRNA levels are sustained with a longer infusion, whereas others show a kinetic decrease and then increase later. Significant up-regulation of genes stimulating osteoclastogenesis in the anabolic regime suggests a provocative and paradoxical theme for the anabolic effect of PTH that a full anabolic response requires a transient up-regulation of genes classically associated with a resorptive response. Ingenuity pathway analysis was performed on the microarray data. A novel signaling network was established that is differentially regulated in the two PTH treatment regimes. Key regulators are suggested to be AREG, CCL2, WNT4, and cAMP-responsive element modulator.

Parathyroid hormone stimulates osteoblastic expression of MCP-1 to recruit and increase the fusion of pre/osteoclasts.

The clinical findings that alendronate blunted the anabolic effect of human parathyroid hormone (PTH) on bone formation suggest that active resorption is involved and enhances the anabolic effect. PTH signals via its receptor on the osteoblast membrane, and osteoclasts are impacted indirectly via the products of osteoblasts. Microarray with RNA from rats injected with human PTH or vehicle showed a strong association between the stimulation of monocyte chemoattractant protein-1 (MCP-1) and the anabolic effects of PTH. PTH rapidly and dramatically stimulated MCP-1 mRNA in the femora of rats receiving daily injections of PTH or in primary osteoblastic and UMR 106-01 cells. The stimulation of MCP-1 mRNA was dose-dependent and a primary response to PTH signaling via the cAMP-dependent protein kinase pathway in vitro. Studies with the mouse monocyte cell line RAW 264.7 and mouse bone marrow proved that osteoblastic MCP-1 can potently recruit osteoclast monocyte precursors and facilitate receptor activator of NF-kappaB ligand-induced osteoclastogenesis and, in particular, enhanced fusion. Our model suggests that PTH-induced osteoblastic expression of MCP-1 is involved in recruitment and differentiation at the stage of multinucleation of osteoclast precursors. This information provides a rationale for increased osteoclast activity in the anabolic effects of PTH in addition to receptor activator of NF-kappaB ligand stimulation to initiate greater bone remodeling.

A comparison between the effects of acetaminophen and celecoxib on bone fracture healing in rats.

OBJECTIVES: This study compared the acute treatment effects of systemic analgesics with (celecoxib) and without anti-inflammatory activity (acetaminophen) on bone fracture healing. STUDY DESIGN: Longitudinal time study of fracture healing in rats. METHODS: Closed, mid diaphyseal femur fractures were produced in female Sprague-Dawley rats. The rats were treated for 10 days after fracture with 60 or 300 mg/kg of acetaminophen, 3 or 6 mg/kg of celecoxib, or vehicle by once-daily oral dosing. Fracture healing was measured after 8 weeks by radiographic examination, mechanical testing, and histology. RESULTS: Radiographic scoring indicated that acute celecoxib treatment significantly impaired fracture healing; acetaminophen treatment had no negative effect. Mechanical testing supported the radiographic observations. No negative effects of celecoxib or acetaminophen treatment on the structural properties (peak torque and torsional rigidity) of the healing femurs were detected. In contrast, celecoxib treatment, but not acetaminophen treatment, significantly reduced the material properties (maximum shear stress and shear modulus) of the healing femurs (P < 0.001). Post-mechanical testing examination of the healing femurs found that 73% of the vehicle-treated or acetaminophen-treated femurs had healed as unions (30/41), 27% failed as incomplete unions (11/41), and none failed as nonunions (0%). In contrast, only 21% of the fractured femurs from the celecoxib treated rats had healed as unions (7/34), 53% failed as incomplete unions (18/34), and 26% failed as nonunions (9/34). The proportion of nonunions among the celecoxib-treated rats was significantly higher compared with the control and acetaminophen-treated rats (P < 0.001). Histologic examination indicated that similar to previous studies, celecoxib treatment, but not acetaminophen treatment, altered normal fracture callus morphology in which cartilage rather than new bone abuts the fracture site. CONCLUSIONS: No negative effect from acute acetaminophen treatment on fracture healing was detected. In contrast, acute treatment with celecoxib, a selective cyclooxygenase-2 inhibitor with anti-inflammatory activity, significantly impaired fracture healing.