CryoET of β-amyloid and tau within postmortem Alzheimer's disease brain.

A defining pathological feature of most neurodegenerative diseases is the assembly of proteins into amyloid that form disease-specific structures. In Alzheimer's disease, this is characterized by the deposition of β-amyloid and tau with disease-specific conformations. The in situ structure of amyloid in the human brain is unknown.

Synthetic extremophiles via species-specific formulations improve microbial therapeutics.

Microorganisms typically used to produce food and pharmaceuticals are now being explored as medicines and agricultural supplements. However, maintaining high viability from manufacturing until use remains an important challenge, requiring sophisticated cold chains and packaging. Here we report synthetic extremophiles of industrially relevant gram-negative bacteria (Escherichia coli Nissle 1917, Ensifer meliloti), gram-positive bacteria (Lactobacillus plantarum) and yeast (Saccharomyces boulardii).

Primary total talus arthroplasty for Hawkins type IV talar neck fracture dislocation.

A woman in her 40s was involved in a motor vehicle collision and sustained a closed Hawkins type IV talar neck fracture dislocation. The injury was treated with reduction, percutaneous pinning and spanning external fixation, followed by definitive treatment with total talus arthroplasty (TTA) 2 months following injury. This is a unique example of definitive management for a severe talar neck fracture dislocation with arthroplasty in the subacute setting.

Wave-Based Outcomes Comparison of Hospitalized COVID-19 Patients: A Retrospective Multicenter Cohort Study From Rural Appalachia.

Background: There has been little to no characterization of the pandemic's effects on rural Central Appalachia, in which health disparities in the pre-COVID-19 era have historically plagued. This is the first study to compare wave-based differences in outcomes of hospitalized patients with COVID-19 in the rural Appalachian region. This study aims to provide a more comprehensive understanding of the effects of the COVID-19 pandemic on large rural communities and Appalachia.

A vibrating ingestible bioelectronic stimulator modulates gastric stretch receptors for illusory satiety.

Effective therapies for obesity require invasive surgical and endoscopic interventions or high patient adherence, making it challenging for patients with obesity to effectively manage their disease. Gastric mechanoreceptors sense distension of the stomach and perform volume-dependent vagal signaling to initiate the gastric phase and influence satiety. In this study, we developed a new luminal stimulation modality to specifically activate these gastric stretch receptors to elicit a vagal afferent response commensurate with mechanical distension.

A Vibrating Ingestible BioElectronic Stimulator Modulates Gastric Stretch Receptors for Illusory Satiety.

Effective therapies for obesity either require invasive surgical or endoscopic interventions or high patient adherence, making it challenging for the nearly 42% of American adults who suffer from obesity to effectively manage their disease. Gastric mechanoreceptors sense distension of the stomach and perform volume-dependent vagal signaling to initiate the gastric phase and influence satiety. In this study, we developed a new luminal stimulation modality to specifically activate these gastric stretch receptors to elicit a vagal afferent response commensurate with mechanical distension.

Enhanced and Stem-Cell-Compatible Effects of Nature-Inspired Antimicrobial Nanotopography and Antimicrobial Peptides to Combat Implant-Associated Infection.

Nature-inspired antimicrobial surfaces and antimicrobial peptides (AMPs) have emerged as promising strategies to combat implant-associated infections. In this study, a bioinspired antimicrobial peptide was functionalized onto a nanospike (NS) surface by physical adsorption with the aim that its gradual release into the local environment would enhance inhibition of bacterial growth. Peptide adsorbed on a control flat surface exhibited different release kinetics compared to the nanotopography, but both surfaces showed excellent antibacterial properties.

Structural basis of broad-spectrum β-lactam resistance in Staphylococcus aureus.

Broad-spectrum β-lactam antibiotic resistance in Staphylococcus aureus is a global healthcare burden. In clinical strains, resistance is largely controlled by BlaR1, a receptor that senses β-lactams through the acylation of its sensor domain, inducing transmembrane signalling and activation of the cytoplasmic-facing metalloprotease domain. The metalloprotease domain has a role in BlaI derepression, inducing blaZ (β-lactamase PC1) and mecA (β-lactam-resistant cell-wall transpeptidase PBP2a) expression.

Surveillance of Isolated Colonic Langerhans Cell Histiocytosis in an Adult: A Case Report.

Langerhans cell histiocytosis (LCH) is a rare disorder involving the proliferation of myeloid-derived dendritic cells. It most commonly affects children aged less than 1 to 2 years old. Langerhans cell histiocytosis in adults is more uncommon with an estimated incidence of 1 to 2 cases per 1 million.

Secondary Extramedullary Myeloma of the Gallbladder: A Case Report.

Extramedullary myeloma (EMM) is an infrequent but well-established manifestation of multiple myeloma (MM), defined as a soft tissue plasma cell neoplasm without bone marrow involvement. Gallbladder involvement in EMM, however, is a very rare occurrence, with only 8 cases found in the English medical literature. Here, we present a case of an older adult male with a gallbladder mass in the presence of increasing serum kappa light chains after a normal bone marrow biopsy confirmed the complete remission of a previous MM diagnosis.

A Case of a Rare, Incidental Discovery of Fibrous Obliteration of an Appendiceal Diverticulum.

Diverticulosis of the appendix (DA) is rare and frequently found incidentally. Some cases are discovered after presenting with similar symptomatology to acute appendicitis, whereas other cases may be completely silent. Fibrous obliteration (FO) is a histologic finding indicative of cellular proliferation secondary to relapses of subclinical inflammatory processes.

MeadoWatch: a long-term community-science database of wildflower phenology in Mount Rainier National Park.

We present a long-term and high-resolution phenological dataset from 17 wildflower species collected in Mt. Rainier National Park, as part of the MeadoWatch (MW) community science project. Since 2013, 457 unique volunteers and scientists have gathered data on the timing of four key reproductive phenophases (budding, flowering, fruiting, and seeding) in 28 plots over two elevational gradients alongside popular park trails.

Heterotopic Pancreas Located at the Gastroesophageal Junction in a Hiatal Hernia: A Case Report.

Heterotopic pancreas, commonly referred to as pancreatic rest or ectopic pancreas, is a congenital anomaly in which pancreatic tissue is anatomically separate from the main pancreatic gland without continuity of a duct system or vascularity. It is commonly found in the upper gastrointestinal tract, specifically in the stomach and small intestine. To date, only about 18 adult cases of heterotopic pancreas in the esophagus have been reported in the English medical literature; seven of which were in women, and five of which originated at the gastroesophageal junction (GEJ).

Resolving physical interactions between bacteria and nanotopographies with focused ion beam scanning electron microscopy.

To robustly assess the antibacterial mechanisms of nanotopographies, it is critical to analyze the bacteria-nanotopography adhesion interface. Here, we utilize focused ion beam milling combined with scanning electron microscopy to generate three-dimensional reconstructions of or interacting with nanotopographies. For the first time, 3D morphometric analysis has been exploited to quantify the intrinsic contact area between each nanostructure and the bacterial envelope, providing an objective framework from which to derive the possible antibacterial mechanisms of synthetic nanotopographies.

Nitric oxide and reactive oxygen species exert opposing effects on the stability of hypoxia-inducible factor-1alpha (HIF-1alpha) in explants of human pial arteries.

Hypoxia induces angiogenesis, partly through stabilization of hypoxia-inducible factor-1alpha (HIF-1alpha), leading to transcription of pro-angiogenic factors. Here we examined the regulation of HIF-1alpha by hypoxia and nitric oxide (NO) in explants of human cerebrovascular smooth muscle cells. Cells were treated with NO donors under normoxic or hypoxic (2% O2) conditions, followed by analysis of HIF-1alpha protein levels.