Feeding tube use is associated with severe scoliosis in patients with cerebral palsy and limited ambulatory ability.

PURPOSE: Cerebral palsy (CP) is the most common motor disorder in childhood. Scoliosis is a common complication of CP that can reach clinically severe levels, but predictors for scoliosis in CP are not well understood. Some variables identified in the literature involve the severity of the brain injury and the presence of hip deformity. We aimed to identify associations with developing severe scoliosis in a prospective cohort of patients with cerebral palsy at higher risk for severe curve progression. METHODS: This study reviewed a prospectively collected database at a tertiary children's hospital. We evaluated a panel of potential associations with severe scoliosis-including age, sex, Gross Motor Function Classification System (GMFCS) class, history of hip surgery, epilepsy, and feeding tube presence-in a population of children with limited ambulatory ability defined as GMFCS level IV or V CP. Univariate analysis and multivariate logistic regression with stepwise selection was used for analysis. RESULTS: Descriptive analysis showed that female sex, higher GMFCS class, history of hip surgery, non-upright seating, pelvic obliquity, presence of epilepsy, and presence of a feeding tube were associated with an increased risk for scoliosis. Multivariate logistic regression analysis revealed that the presence of a feeding tube was associated with severe scoliosis even when controlling for GMFCS and age. CONCLUSIONS: Feeding tube use may stratify risk for severe scoliosis progression in patients with GMFCS IV or V CP.

Fluid-Guided CVD Growth for Large-Scale Monolayer Two-Dimensional Materials.

Atmospheric pressure chemical vapor deposition (APCVD) has been used extensively for synthesizing two-dimensional (2D) materials because of its low cost and promise for high-quality monolayer crystal synthesis. However, the understanding of the reaction mechanism and the key parameters affecting the APCVD processes is still in its embryonic stage. Hence, the scalability of the APCVD method in achieving large-scale continuous film remains very poor. Here, we use MoSe2 as a model system and present a fluid guided growth strategy for understanding and controlling the growth of 2D materials. Through the integration of experiment and computational fluid dynamics (CFD) analysis in the full-reactor scale, we identified three key parameters, precursor mixing, fluid velocity, and shear stress, which play a critical role in the APCVD process. By modifying the geometry of the growth setup to enhance precursor mixing and decrease nearby velocity shear rate and adjusting flow direction, we have successfully obtained inch-scale monolayer MoSe2. This unprecedented success of achieving scalable 2D materials through fluidic design lays the foundation for designing new CVD systems to achieve the scalable synthesis of nanomaterials.

Mechanistic insights into the protective roles of polyphosphate against amyloid cytotoxicity.

The universally abundant polyphosphate (polyP) accelerates fibril formation of disease-related amyloids and protects against amyloid cytotoxicity. To gain insights into the mechanism(s) by which polyP exerts these effects, we focused on α-synuclein, a well-studied amyloid protein, which constitutes the major component of Lewy bodies found in Parkinson's disease. Here, we demonstrate that polyP is unable to accelerate the rate-limiting step of α-synuclein fibril formation but effectively nucleates fibril assembly once α-synuclein oligomers are formed. Binding of polyP to α-synuclein either during fibril formation or upon fibril maturation substantially alters fibril morphology and effectively reduces the ability of α-synuclein fibrils to interact with cell membranes. The effect of polyP appears to be α-synuclein fibril specific and successfully prevents the uptake of fibrils into neuronal cells. These results suggest that altering the polyP levels in the extracellular space might be a potential therapeutic strategy to prevent the spreading of the disease.

Targeting the unfolded protein response in head and neck and oral cavity cancers.

Many FDA-approved anti-cancer therapies, targeted toward a wide array of molecular targets and signaling networks, have been demonstrated to activate the unfolded protein response (UPR). Despite a critical role for UPR signaling in the apoptotic execution of cancer cells by many of these compounds, the authors are currently unaware of any instance whereby a cancer drug was developed with the UPR as the intended target. With the essential role of the UPR as a driving force in the genesis and maintenance of the malignant phenotype, a great number of pre-clinical studies have surged into the medical literature describing the ability of dozens of compounds to induce UPR signaling in a myriad of cancer models. The focus of the current work is to review the literature and explore the role of the UPR as a mediator of chemotherapy-induced cell death in squamous cell carcinomas of the head and neck (HNSCC) and oral cavity (OCSCC), with an emphasis on preclinical studies.

Polyphosphate Stabilizes Protein Unfolding Intermediates as Soluble Amyloid-like Oligomers.

Inorganic polyphosphate (polyP) constitutes one of the most conserved and ubiquitous molecules in biology. Recent work in bacteria demonstrated that polyP increases oxidative stress resistance by preventing stress-induced protein aggregation and promotes biofilm formation by stimulating functional amyloid formation. To gain insights into these two seemingly contradictory functions of polyP, we investigated the effects of polyP on the folding model lactate dehydrogenase. We discovered that the presence of polyP during the thermal unfolding process stabilizes folding intermediates of lactate dehydrogenase as soluble micro-ß-aggregates with amyloid-like properties. Size and heterogeneity of the oligomers formed in this process were dependent on the polyP chain length, with longer chains forming smaller, more homogenous complexes. This ability of polyP to stabilize thermally unfolded proteins even upon exposure to extreme temperatures appears to contribute to the observed resistance of uropathogenic Escherichia coli toward severe heat shock treatment. These results suggest that the working mechanism of polyP is the same for both soluble and amyloidogenic proteins, with the ultimate outcome likely being determined by a combination of polyP chain length and the client protein itself. They help to explain how polyP can simultaneously function as general stress-protective chaperone and instigator of amyloidogenic processes in vivo.

Is Industry Funding Associated with Greater Scholarly Impact Among Academic Neurosurgeons?

OBJECTIVE: To determine the relationship between industry payments and scholarly impact among academic neurosurgeons. METHODS: Faculty names and academic rank data were obtained from department websites, bibliometric data were obtained from the Scopus database, and industry payment data were obtained from the Center for Medicare and Medicaid Services open payments database (openpayments.cms.gov). The h-index was used to estimate scholarly impact. Payments were classified as "general," "associated research," and "research payments." Subgroup analyses were done for academic rank, fellowship training, and sex. RESULTS: Among 1008 academic neurosurgeons, scholarly impact was greater among individuals receiving associated research industry support compared with those not receiving it. Scholarly impact also was greater among individuals who received more than $10,000 of any type of industry support compared with individuals who received less than that or no payment. This association also was seen in fellowship-trained surgeons. Female neurosurgeons were less likely than male neurosurgeons to get industry funding and were likely to get less funding. CONCLUSIONS: There is a strong association between associated research funding from industry and scholarly impact among academic neurosurgeons. It's unclear whether this association is a result of funding facilitating more research projects that eventually lead to more high-impact publications, if industry is providing more funding to academic neurosurgeons with greater scholarly impact, or whether it represents intrinsic academic activity among a group of neurosurgeons who are more likely to be academically productive and procure funding from all potential sources to increase this activity.