Designing a Locally Manufacturable Wheelchair for Nepal

People with disabilities in developing countries often lack the basic equipment needed to assist them in their daily lives. International Nepal Fellowship (INF) is a Christian medical organization located in Nepal that provides medical care and assistance to people with disabilities and other conditions. Currently, INF imports expensive wheelchairs that undergo a prolonged border process before being received. INF has reached out to the Collaboratory to design a wheelchair that can withstand the challenges of Nepal’s terrain and can be manufactured from local materials. The Nepal Wheelchair team has set out to design a wheelchair that can fulfill their needs. In previous work, the team researched wheelchair designs and took a trip to Nepal. From this trip, more information was gained, an initial prototype was constructed, and locally available materials and parts from Nepal were brought back. This year, as a result of knowledge gained through constructing the second prototype, many design changes were tested and implemented. The team researched standards and created testing procedures to ensure the changes to the rear wheel mount, caster wheel mount, footrest, and seat design would uphold the strength and durability of the wheelchair. These design changes have enhanced patient safety and experience in the wheelchair while still keeping the design easily manufacturable. The team also researched options for adding push rims and through using a roller bender were able to construct them. Moving forward, the team will continue to finalize manufacturing documentation and take a second trip to Nepal this May. Funding for this work provided by The Collaboratory for Strategic Partnerships and Applied Research.https://mosaic.messiah.edu/engr2022/1012/thumbnail.jp

Scavenging by threatened turtles regulates freshwater ecosystem health during fish kills

Humans are increasing the frequency of fish kills by degrading freshwater ecosystems. Simultaneously, scavengers like freshwater turtles are declining globally, including in the Australian Murray–Darling Basin. Reduced scavenging may cause water quality problems impacting both ecosystems and humans. We used field and mesocosm experiments to test whether scavenging by turtles regulates water quality during simulated fish kills. In the field, we found that turtles were important scavengers of fish carrion. In mesocosms, turtles rapidly consumed carrion, and water quality in mesocosms with turtles returned to pre-fish kill levels faster than in turtle-free controls. Our experiments have important ecological implications, as they suggest that turtles are critical scavengers that regulate water quality in freshwater ecosystems. Recovery of turtle populations may be necessary to avoid the worsening of ecosystem health, particularly after fish kills, which would have devastating consequences for many freshwater species

A novel class of 3-(phenoxy-phenyl-methyl)-pyrrolidines as potent and balanced norepinephrine and serotonin reuptake inhibitors: Synthesis and structure-activity relationships

a b s t r a c t A series of 3-(phenoxy-phenyl-methyl)-pyrrolidine analogues were discovered to be potent and balanced norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors. Several of these compounds were identified to have suitable in vitro pharmacokinetic properties for an orally dosed and CNS-targeted drug. Compound 39b, in particular, was identified as a potent NET and SERT reuptake inhibitor (NSRI) with minimal off-target activity and demonstrated robust efficacy in the spinal nerve ligation model of pain behavior

Quantitative Proteomics Reveals Myosin and Actin as Promising Saliva Biomarkers for Distinguishing Pre-Malignant and Malignant Oral Lesions

Oral cancer survival rates increase significantly when it is detected and treated early. Unfortunately, clinicians now lack tests which easily and reliably distinguish pre-malignant oral lesions from those already transitioned to malignancy. A test for proteins, ones found in non-invasively-collected whole saliva and whose abundances distinguish these lesion types, would meet this critical need.To discover such proteins, in a first-of-its-kind study we used advanced mass spectrometry-based quantitative proteomics analysis of the pooled soluble fraction of whole saliva from four subjects with pre-malignant lesions and four with malignant lesions. We prioritized candidate biomarkers via bioinformatics and validated selected proteins by western blotting. Bioinformatic analysis of differentially abundant proteins and initial western blotting revealed increased abundance of myosin and actin in patients with malignant lesions. We validated those results by additional western blotting of individual whole saliva samples from twelve other subjects with pre-malignant oral lesions and twelve with malignant oral lesions. Sensitivity/specificity values for distinguishing between different lesion types were 100%/75% (p = 0.002) for actin, and 67%/83% (p<0.00001) for myosin in soluble saliva. Exfoliated epithelial cells from subjects' saliva also showed increased myosin and actin abundance in those with malignant lesions, linking our observations in soluble saliva to abundance differences between pre-malignant and malignant cells.Salivary actin and myosin abundances distinguish oral lesion types with sensitivity and specificity rivaling other non-invasive oral cancer tests. Our findings provide a promising starting point for the development of non-invasive and inexpensive salivary tests to reliably detect oral cancer early

Vitamin D Receptor-Mediated Stromal Reprogramming Suppresses Pancreatitis and Enhances Pancreatic Cancer Therapy

Summary The poor clinical outcome in pancreatic ductal adenocarcinoma (PDA) is attributed to intrinsic chemoresistance and a growth-permissive tumor microenvironment. Conversion of quiescent to activated pancreatic stellate cells (PSCs) drives the severe stromal reaction that characterizes PDA. Here, we reveal that the vitamin D receptor (VDR) is expressed in stroma from human pancreatic tumors and that treatment with the VDR ligand calcipotriol markedly reduced markers of inflammation and fibrosis in pancreatitis and human tumor stroma. We show that VDR acts as a master transcriptional regulator of PSCs to reprise the quiescent state, resulting in induced stromal remodeling, increased intratumoral gemcitabine, reduced tumor volume, and a 57% increase in survival compared to chemotherapy alone. This work describes a molecular strategy through which transcriptional reprogramming of tumor stroma enables chemotherapeutic response and suggests vitamin D priming as an adjunct in PDA therapy