7,9-Diaryl-1,6,8-trioxaspiro[4.5]dec-3-en-2-ones: readily accessible and highly potent anticancer compounds.

7,9-Diaryl-1,6,8-trioxaspiro[4.5]dec-3-en-2-ones are a recently described group of spirocyclic butenolides that can be generated rapidly and as a single diastereomer through a cascade process between γ-hydroxybutenolides and aromatic aldehydes. The following outlines our findings that these spirocycles are potently cytotoxic and have a dramatic structure-function profile that provides excellent insight into the structural features required for this potency.

Degloving Traumatic Lesser Toe Injury Reconstruction with Full-Thickness Skin Graft from Partially Amputated Autologous Toe Donor Site: A Case Report.

Complex soft-tissue injuries consist of difficult traumatic injuries caused by high-energy mechanisms such as motor vehicle accidents, lawnmower injuries, and crush injuries from heavy objects. Many times, because of the high-energy trauma, there is significant damage to the soft tissue and underlying bone, leading to a complex situation for healing. In this case report, a 43-year-old woman presented with extensive degloving injury and open fractures of the forefoot resulting from a lawnmower accident. After extensive irrigation and debridement, wound closure was achieved using a full-thickness skin graft (FTSG). Although many case reports have been published about management of these complex soft-tissue injuries, there are no reports on using an autologous FTSG from a neighboring digit undergoing distal amputation for wound coverage. This report discusses the technique of using an autologous FTSG from an amputated specimen to achieve wound coverage with adequate limb salvage principles.

Efficacy of Dehydrated Human Amnion Chorion Membrane in the Treatment of Diabetic Foot Ulcers: A Review.

Studies have been conducted to evaluate the efficacy of dehydrated human amnion chorion membrane (dHACM) in treating recalcitrant diabetic foot ulcers. A literature search was performed to review the data collected from the use of dHACM allografts. Two products were explicitly named in these publications, EpiFix and AmnioBand Membrane. Relevant results included the healing rate, number of wounds healed, and number of grafts used. Data had supported the potential of lowering the overall cost to manage a wound despite a relatively higher cost per dressing. However, discrepancy was observed in the rate of healing between several of the studies. Nonetheless, dHACM had demonstrated improvement in healing of recalcitrant diabetic foot ulcers compared to standard of care alone. These results provide grounds for more inclusive research on dHACM in the future.

Retronychia: A Literature Review.

Retronychia is an uncommonly reported condition among the category of nail pathologies. It often presents mimicking similar nail disorders, such as onychocryptosis, onychomycosis, and paronychia. This pathologic condition has recently seen an increased presence in the literature, mainly in the form of case studies. Literature on retronychia was collected using PubMed, the US National Library of Medicine, the National Institutes of Health's online database, life science journals, and online books. References cited by these articles were also reviewed for additional relevant publications. Reviews, case studies, and retrospective articles were compiled and analyzed for commonalities in cause, patient demographics, clinical signs, and treatment. Retronychia may be more common than previously suggested. Proper knowledge and education of this pathologic nail condition is important to health-care professionals to achieve early and correct diagnosis.

Fibrodysplasia Ossificans Progressiva and Its Implications in Podiatric Medicine: A Case Report.

The purpose of this case report is to show the clinical presentation of a rare genetic disorder, called fibrodysplasia ossificans progressiva, on the development of the foot in a newborn. Shortened great toes and malformations of the first metatarsals are present in all affected individuals at birth. Irreversible heterotopic endochondral ossification of soft tissues occurs in the first decade of life, often resulting in permanent immobility by the third decade of life. Trauma caused by surgical excision of nodules, dental procedures, or injections can further exacerbate this condition. Early diagnosis is imperative for these patients to prevent irreversible damage that may result from unnecessary invasive interventions. This case report presents a boy aged 2 years 3 months who was born with bilateral bunion deformity. The goal is to raise awareness of this disorder in the podiatric community, especially for those who work with pediatric patients.

Gastrin stimulates a cholecystokinin-2-receptor-expressing cardia progenitor cell and promotes progression of Barrett's-like esophagus.

OBJECTIVE: The incidence of esophageal adenocarcinoma (EAC) is increasing, but factors contributing to malignant progression of its precursor lesion, Barrett's esophagus (BE), have not been defined. Hypergastrinemia caused by long-term use of proton pump inhibitors (PPIs), has been suggested as one possible risk factor. The gastrin receptor, CCK2R, is expressed in the cardia and upregulated in BE, suggesting the involvement of the gastrin-CCK2R pathway in progression. In the L2-IL-1ß mouse model, Barrett's-like esophagus arises from the gastric cardia. Therefore, we aimed to analyze the effect of hypergastrinemia on CCK2R+ progenitor cells in L2-IL-1ß mice. DESIGN: L2-IL-1ß mice were mated with hypergastrinemic (INS-GAS) mice or treated with PPIs to examine the effect of hypergastrinemia in BE progression. CCK2R-CreERT crossed with L2-IL-1ß mice were used to analyze the lineage progenitor potential of CCK2R+ cells. Cardia glands were cultured in vitro, and the effect of gastrin treatment analyzed. L2-IL-1ß mice were treated with a CCK2R antagonist YF476 as a potential chemopreventive drug. RESULTS: Hypergastrinemia resulted in increased proliferation and expansion of Barrett's-like esophagus. Lineage tracing experiments revealed that CCK2R+ cells are long-lived progenitors that can give rise to such lesions under chronic inflammation. Gastrin stimulated organoid growth in cardia culture, while CCK2R inhibition prevented Barrett's-like esophagus and dysplasia. CONCLUSIONS: Our data suggest a progression model for BE to EAC in which CCK2R+ progenitor cells, stimulated by hypergastrinemia, proliferate to give rise to metaplasia and dysplasia. Hypergastrinemia can result from PPI use, and the effects of hypergastrinemia in human BE should be studied further.

What's Next for Gastrointestinal Disorders: No Needles?

A myriad of pathologies affect the gastrointestinal tract, citing this affected area as a significant target for therapeutic intervention. One group of therapeutic agents, antisense and oligonucleotides and small interfering RNAs, offer a promising platform for treating a wide variety of diseases ranging from cancer to auto-immune diseases. Current delivery methods are carried out either systemically or locally into diseased areas, both of which involve needles. The challenge in orally administering this type of treatment lies in the complications that arise due to the vast environmental extremes found within the gastrointestinal tract, owing to the fact that, as the drug travels down the gastrointestinal tract, it is subjected to pH changes and interactions with bacteria and a variety of digestive and protective enzymes including proteases, DNAses, and RNAses. Overcoming these challenges to allow the practical application of these drugs is a priority that has invoked a multitude of research in the chemical, biological, and material sciences. In this review, we will address common gastrointestinal pathologies, the barriers to oral-based therapies and antisense-interfering technologies, the approaches that have already been applied for their delivery, and the current status of antisense drug therapy clinical trials for gastrointestinal-related disorders.