A Geospatial Analysis of Social and Structural Determinants of Health and High HIV Prevalence in Alabama, USA.

OBJECTIVE: This study utilizes geospatial analytic techniques to examine HIV hotspots in Alabama leveraging Medicaid utilization data. METHODS: This cross-sectional study leveraged Medicaid utilization data from Alabama's 67 counties, averaging 9,861 Medicaid recipients aged > 18 years old per county. We used Alabama Medicaid administrative claims data from January 1, 2016, to December 31, 2020, to identify individuals with HIV. Using Microsoft SQL Server, we obtained the average annual count of HIV Medicaid claims in each of the 67 Alabama counties (numerator) and the number of adult Medicaid recipients in each county (denominator), and standardized with a multiplier of 100,000. We also examined several other area-level summary variables (e.g., non-high school completion, income greater than four times the federal poverty level, social associations, urbanicity/rurality) as social and structural determinants of health. County-boundary choropleth maps were created representing the geographic distribution of HIV rates per 100,000 adult Medicaid recipients in Alabama. Leveraging ESRI ArcGIS and local indicators of spatial association (LISA), results were examined using local Moran's I to identify geographic hotspots. RESULTS: Eleven counties had HIV rates higher than 100 per 100,000. Three were hotspots. Being an HIV hotspot was significantly associated with relatively low educational attainment and less severe poverty than other areas in the state. CONCLUSIONS: Findings suggesting that the HIV clusters in Alabama were categorized by significantly less severe poverty and lower educational attainment can aid ongoing efforts to strategically target resources and end the HIV epidemic in U.S.' Deep South.

Generalization of procedural motor sequence learning after a single practice trial.

When humans begin learning new motor skills, they typically display early rapid performance improvements. It is not well understood how knowledge acquired during this early skill learning period generalizes to new, related skills. Here, we addressed this question by investigating factors influencing generalization of early learning from a skill A to a different, but related skill B. Early skill generalization was tested over four experiments (N = 2095). Subjects successively learned two related motor sequence skills (skills A and B) over different practice schedules. Skill A and B sequences shared ordinal (i.e., matching keypress locations), transitional (i.e., ordered keypress pairs), parsing rule (i.e., distinct sequence events like repeated keypresses that can be used as a breakpoint for segmenting the sequence into smaller units) structures, or possessed no structure similarities. Results showed generalization for shared parsing rule structure between skills A and B after only a single 10-second practice trial of skill A. Manipulating the initial practice exposure to skill A (1 to 12 trials) and inter-practice rest interval (0-30 s) between skills A and B had no impact on parsing rule structure generalization. Furthermore, this generalization was not explained by stronger sensorimotor mapping between individual keypress actions and their symbolic representations. In contrast, learning from skill A did not generalize to skill B during early learning when the sequences shared only ordinal or transitional structure features. These results document sequence structure that can be very rapidly generalized during initial learning to facilitate generalization of skill.

Bioactive impact of manuka honey and bone char incorporated into gelatin and chitosan cryogels in a rat calvarial fracture model.

Bone tissue engineered scaffolds are designed to mimic the natural environment for regeneration when typical healing is inhibited. Autografts are the current gold standard for treatment but are limited by available bone and supplementary surgical sites that broaden complications and comorbidities. Cryogels are an ideal scaffold in bone regeneration due to their mechanical integrity and marcoporous structure that elicits angiogenesis and subsequently new bone tissue formation. To aid in bioactivity and osteoinductivity, manuka honey (MH) and bone char (BC) were added to gelatin and chitosan cryogels (CG). Manuka honey has powerful antimicrobial properties to aid against graft infection, and bone char is composed of 90% hydroxyapatite, a well-studied bioactive material. These additives are natural, abundant, easy to use, and cost effective. CG cryogels incorporated with either BC or MH, and plain CG cryogels were implanted into rat calvarial fracture models for cortical bone regeneration analysis. We found indication of bioactivity with both bone char and manuka honey through the presence of woven bone structure in histology stains and micro computed tomography (microCT) data. Overall, plain CG cryogels supported greater bone regeneration capabilities than the BC or MH incorporated cryogels due to a lack of advanced organized tissue formation and collagen deposition after 8 weeks of implantation; however, future work should explore varying additive concentrations and delivery methods to further assess additive potential.

Aryl hydrocarbon receptor is regulated via multiple mechanisms in human keratinocytes.

Aryl hydrocarbon receptor (AhR) is a basic helix-loop-helix transcription factor activated by polycyclic aromatic hydrocarbons of synthetic and natural origin. While a number of novel AhR ligands have been recently identified, little is known about their possible influence on AhR levels and stability. We used western blot, qRT-PCR and immunocytochemistry to determine the effects of AhR ligands on AhR expression in N-TERT (N-TERT1) immortalized human keratinocytes, and immunohistochemistry to assess patterns of AhR expression in human and mouse skin and skin appendages. While AhR was highly expressed in cultured keratinocytes and in the skin, it was found primarily in the cytoplasm, but not in the nucleus, suggesting its inactivity. At the same time, treatment of N-TERT cells with proteasomal inhibitor MG132 and eventual inhibition of AhR degradation resulted in nuclear AhR accumulation. Treatment of keratinocytes with AhR ligands such as TCDD, FICZ, caused near-complete disappearance of AhR, and treatment with I3C resulted in substantially diminished level of AhR possibly due to ligand-induced AhR degradation. The AhR decay was blocked by proteasome inhibition, indicating degradation-based mechanism of regulation. Additionally, AhR decay was blocked by ligand-selective AhR antagonist CH223191, implying substrate-induced mechanism of degradation. Furthermore, degradation of AhR was blocked in N-TERT cells with knockdown of AhR dimerization partner ARNT (HIF1ß), suggesting that ARNT is required for AhR proteolysis. However, addition of hypoxia mimetics (HIF1 pathway activators) CoCl2 and DMOG had only minor effects on degradation of AhR. Additionally, inhibition of HDACs with Trichostatin A resulted in enhanced expression of AhR in both untreated and ligand-treated cells. These results demonstrate that in immortalized epidermal keratinocytes AhR is primarily regulated post-translationally via proteasome-mediated degradation, and suggest potential means to manipulate AhR levels and signaling in the skin. Overall, the AhR is regulated via multiple mechanisms, including proteasomal ligand- and ARNT-dependent degradation, and transcriptional regulation by HDACs, implying complex system of balancing its expression and protein stability.

Human papillomavirus prevalence among unvaccinated young female college students in Botswana: A cross-sectional study.

BACKGROUND: Human papillomavirus (HPV) is a sexually transmitted infection and a causative agent of cervical cancer. It is common in adolescent girls and young women, and the majority of infections are transient and asymptomatic. In Botswana, there are currently no data on the HPV prevalence against which the impact of prophylactic HPV vaccines can be measured. OBJECTIVES: To establish a baseline HPV prevalence in an unvaccinated cohort of young women. METHODS: Women aged ≥18 years were recruited from the University of Botswana between September 2016 and May 2020. Demographic and behavioural characteristics of participants were collected. Subsequently, cervicovaginal swabs were obtained and tested for HPV using polymerase chain reaction-restriction fragment length polymorphism. We determined the prevalent HPV types, and evaluated the risk factors associated with HPV positivity. RESULTS: A total of 978 young women were recruited. Overall, there were 589 (60.2%) participants with HPV infection and 12 (1.2%) with HIV. The median (interquartile range) age of the study participants was 19 (18 - 20) years. Multivariate logistic regression analysis showed that significant factors associated with HPV positivity were sexual activity (adjusted odds ratio (aOR) 2.06; 95% confidence interval (CI) 1.49 - 2.63; p<0.001), number of sex partners ≥3 (aOR 2.10; 95% CI 1.39 - 3.18; p<0.001), and smoking (aOR 2.00; 95% CI 1.26 - 3.20; p=0.004). CONCLUSION: Our results demonstrate for the first time the prevalence of HPV in unvaccinated young women in Botswana. We found a high prevalence of HPV infection, with statistical differences with different risk factors. This finding supports the need for HPV vaccination strategies for females prior to sexual debut to reduce the future burden of cervical cancer in Botswana.

COVID-19: smoke testing of surgical mask and respirators.

BACKGROUND: Fluid Resistant Surgical Masks have been implemented in UK personal protective equipment (PPE) guidelines for COVID-19 for all care sites that do not include aerosol-generating procedures (AGPs). FFP3 masks are used in AGP areas. Concerns from the ENT and plastic surgery communities out with intensive care units have questioned this policy. Emerging evidence on cough clouds and health care worker deaths has suggested that a review is required. AIMS: To test the efficacy of Fluid Resistant Surgical Mask with and without adaptions for respiratory protection. To test the efficacy of FFP and FFP3 regarding fit testing and usage. METHODS: A smoke chamber test of 5 min to model an 8-h working shift of exposure while wearing UK guideline PPE using an inspiratory breathing mouthpiece under the mask. Photographic data were used for comparison. RESULTS: The Fluid Resistant Surgical Mask gave no protection to inhaled smoke particles. Modifications with tape and three mask layers gave slight benefit but were not considered practical. FFP3 gave complete protection to inhaled smoke but strap tension needs to be 'just right' to prevent facial trauma. Facial barrier creams are an infection risk. CONCLUSIONS: Surgical masks give no protection to respirable particles. Emerging evidence on cough clouds and health care worker deaths suggests the implementation of a precautionary policy of FFP3 for all locations exposed to symptomatic or diagnosed COVID-19 patients. PPE fit testing and usage policy need to improve to include daily buddy checks for FFP3 users.

The gridded retarding ion drift sensor for the petitSat cubeSat mission.

The Gridded Retarding Ion Drift Sensor (GRIDS) is a small sensor that will fly on the 6 U petitSat CubeSat. It is designed to measure the three-dimensional plasma drift velocity vector in the Earth's ionosphere. The GRIDS also supplies information about the ion temperature, ion density, and the ratio of light to heavy ions present in the ionospheric plasma. It utilizes well-proven techniques that have been successfully validated by similar instruments on larger satellite missions while meeting CubeSat-compatible requirements for low mass, size, and power consumption. GRIDS performs the functions of a Retarding Potential Analyzer (RPA) and an Ion Drift Meter (IDM) by combining the features of both types of instruments in a single package. The sensor alternates RPA and IDM measurements to produce the full set of measurement parameters listed above. On the petitSat mission, GRIDS will help identify and characterize a phenomenon known as plasma blobs (or enhancements).

Improving understanding of type 2 diabetes remission: research recommendations from Diabetes UK's 2019 remission workshop.

AIM: To describe the process and outputs of a workshop convened to identify key priorities for future research in the area of remission of type 2 diabetes, and provide recommendations to researchers and research funders on how best to address them. With the ultimate aim of enabling the remission of type 2 diabetes to become a possibility for more people. METHODS: A 1-day research workshop was conducted, bringing together 31 researchers, people living with diabetes, healthcare professionals and members of staff from Diabetes UK to identify and prioritize recommendations for future research into remission of type 2 diabetes. RESULTS: Workshop attendees identified 10 key themes for further research. Four of these themes were prioritized for further focus: (i) understanding how to personalize lifestyle approaches based on biology, patient choice and subtypes; (ii) understanding the biology of remission; (iii) understanding the most effective approaches to implementation of lifestyle interventions; and (iv) understanding the best approaches to combining therapies (gut hormones, other drugs, lifestyle approaches and bariatric surgery). CONCLUSIONS: This paper outlines recommendations to address the current gaps in knowledge related to remission of type 2 diabetes.

Transforming mental well-being for people with diabetes: research recommendations from Diabetes UK's 2019 Diabetes and Mental Well-Being Workshop.

AIMS: To identify key gaps in the research evidence base that could help to improve the mental well-being of people with diabetes, and to provide recommendations to researchers and research funders on how best to address them. METHODS: A 2-day international research workshop was conducted, bringing together research experts in diabetes and in mental health, people living with diabetes and healthcare professionals. RESULTS: The following key areas needing increased financial investment in research were identified: understanding the mechanisms underlying depression; understanding the multifactorial impact of social stigma; improving the language used by healthcare professionals; supporting people who find it difficult to engage with their diabetes; supporting significant others; supporting people with diabetes and eating disorders; improving models of care by learning from best practice; the potential benefits of screening and managing diabetes distress in routine diabetes care pathways; primary prevention of mental health issues at the time of diagnosis of diabetes; establishing the effectiveness of diabetes therapies on mood and other mental health issues; and understanding the impact of current diabetes technologies on mental health. Research recommendations as to how to address each of these priority areas were also developed. CONCLUSIONS: This inaugural position statement outlines recommendations to address the urgent unmet need related to the mental well-being of people living with diabetes, and calls on the research community and funders to develop research programmes and strategies to reduce this need.

A 24-month cost and outcome analysis comparing traditional fronto-orbital advancment and remodeling with endoscopic strip craniectomy and molding helmet in the management of unicoronal craniosynostosis: A retrospective bi-institutional review.

INTRODUCTION: Endoscopic strip craniectomy with helmeting (ESCH) has been shown to be a safe and efficacious alternative to fronto-orbital remodeling (FOR) for selected children with craniosynostosis. In addition to clinical factors, there may be economic benefits from the use of ESCH instead of FOR. METHODS: A retrospective review of 23 patients with nonsyndromic unicoronal craniosynostosis (UCS) treated with FOR was carried out at Great Ormond Street Hospital (GOSH) for Children in London, UK. Secondary data were used for the ESCH cohort from a paper published by Jimenez and Barone (2013). Data were collected on surgical time, transfusion rates, length of hospital stay, adverse event rates, reintervention rates, and overall costs. Costs were categorized and then assigned to the appropriate data sets. RESULTS: The mean age of patients undergoing FOR (vs. ESCH) was 17.4 mo (vs. 3.1 mo) with a mean surgical time of 234 min (vs. 55 min), mean transfusion volume of 221.6 mL (vs. 80.0 mL), mean transfusion rate of 14/23 (vs. 2/115), and a total immediate overnight stay of 3.13 days (vs. 97% next-day discharge). The FOR group had a higher adverse event rate (5/23 vs. 4/115, p=<0.005) and a higher number requiring extraocular muscle surgery (4/23 vs. 7/109, p=0.16). There was a substantial difference in overall costs between the two groups. Total variance cost for the FOR group was £7436.5 vs. £4951.35, representing a cost difference of £2485.15 over the 24-month study period. CONCLUSION: ESCH, in comparison to FOR, appears as a more economical method in the management of USC patients, as well as having clinical benefits including reduced adverse event rate and improved ophthalmic outcomes.

The prediction of far-infrared spectra for planetary nitrile ices using periodic density functional theory with comparison to thin film experiments.

Future spacecraft missions to planetary systems, Trans-Neptunian objects, and cometary bodies could implement far-infrared surveys to confirm the presence of condensed-phase species via their unique lattice features. For composite molecular ices of astrophysical significance, laboratory reference spectra are required to provide absorption coefficients used to quantify solid-state abundances. However, due to strong intermolecular interactions in polar ice systems, laboratory data of mixed-phase ices are difficult to interpret. In this study we have applied periodic density functional theory code to model bulk molecular crystals. This method allows for more accurate simulation of thin-film spectra than approaches simulating small clusters. For this proof-of-principle study on a series of pure nitrile ices of planetary interest, our simulated far-infrared spectra show excellent agreement to data from thin film studies performed at the Australian Synchrotron (crystalline acetonitrile and propionitrile) and to previously published spectra (hydrogen cyanide, acrylonitrile, cyanoacetylene, and cyanogen). The combined theoretical and experimental approach has provided a new explanation for the asymmetric profile of the hydrogen cyanide lattice feature and a more systematic assignment of nitrile ice absorption bands to low-frequency lattice modes. We nominate prominent absorption features for the detection of crystalline nitrile carriers located on planetary surfaces.

Health-related quality of life of survivors of childhood acute lymphoblastic leukemia: a systematic review.

PURPOSE: Acute lymphoblastic leukemia (ALL) survivors are the largest group of childhood cancer survivors; however, their risk for late effects is high. Cancer-related late effects have the potential to compromise health-related quality of life (HRQL) long into survivorship. None of the reviews so far have focused on ALL solely, but described HRQL for all childhood cancers. We aimed to identify ALL survivors at risk for poor HRQL and identify possible risk factors. METHOD: Following PRISMA guidelines, we performed a systematic review, searching published literature in Pubmed, PsycInfo, Embase, and the Cochrane database including all publications up to December 16, 2016. Two independent reviewers (JV and ER) screened eligible articles and assessed article quality. RESULTS: We found 31 studies representing 4356 survivors and 901 proxies. Thirteen studies found worse, eight found no difference, and three better, overall HRQL scores compared with healthy controls or norms. ALL survivors typically had better overall HRQL scores than survivors of other childhood cancers. Clinical variables (e.g., treatment received) were not consistently associated with HRQL; however, experiencing worse late effects was associated with lower HRQL. Survivor and parent socio-demographic factors and psychological factors such as resilience and depression were also associated with HRQL. CONCLUSION: ALL survivors appeared to have worse or equivalent HRQL compared with controls, but better HRQL than survivors of other cancer types. However, studies reported a wide variability in HRQL and potential risk factors for poor HRQL. Measuring ALL survivors' HRQL longitudinally and comprehensively assessing potential risk factors might identify future avenues to intervene early.

On the role of the second-order derivative term in the calculation of convergent beam diffraction patterns.

The simulation of (scanning) transmission electron microscopy images and diffraction patterns is most often performed using the forward-scattering approximation where the second-order derivative term in z is assumed to be small with respect to the first-order derivative term in the modified Schrödinger equation. This assumption is very good at high incident electron energies, but breaks down at low energies. In order to study the differences between first- and second-order methods, convergent beam electron diffraction patterns were simulated for silicon at the [111] zone-axis orientation at 20 keV and compared using electron intensity difference maps and integrated intensity profiles. The geometrical differences in the calculated diffraction patterns could be explained by an Ewald surface analysis. Furthermore, it was found that solutions based on the second-order derivative equation contained small amplitude oscillations that need to be resolved in order to ensure numerical integration stability. This required the use of very small integration steps resulting in significantly increased computation time compared to the first-order differential equation solution. Lastly, the efficiency of the numerical integration technique is discussed.

Infrared characterisation of acetonitrile and propionitrile aerosols under Titan's atmospheric conditions.

Pure, crystalline acetonitrile (CH3CN) and propionitrile (CH3CH2CN) particles were formed in a collisional cooling cell allowing for infrared (IR) signatures to be compiled from 50 to 5000 cm-1. The cell temperature and pressure conditions were controlled to simulate Titan's lower atmosphere (80-130 K and 1-100 mbar), allowing for the comparison of laboratory data to the spectra obtained from the Cassini-Huygens mission. The far-IR features confirmed the morphology of CH3CN aerosols as the metastable ß-phase (monoclinic) ice, however, a specific crystalline phase for CH3CH2CN could not be verified. Mie theory and the literature complex refractive indices enabled of the experimental spectra to be modelled. The procedure yielded size distributions for CH3CN (55-140 nm) and CH3CH2CN (140-160 nm) particles. Effective kinetic profiles, tracing the evolution of aerosol band intensities, showed that condensation of CH3CH2CN proceeded at twice the rate of CH3CN aerosols. In addition, the rate of CH3CH2CN aerosol depletion via lateral diffusion of the particles from the interrogation volume was approximately 50% faster than that of CH3CN. The far-IR spectra recorded for both nitrile aerosols did not display absorption profiles that could be attributed to the unassigned 220 cm-1 feature, which has been observed to fluctuate seasonally in the spectra obtained from Titan's atmosphere.

The oncogenic MicroRNA Hsa-miR-155-5p targets the transcription factor ELK3 and links it to the hypoxia response.

The molecular response to hypoxia is a critical cellular process implicated in cancer, and a target for drug development. The activity of the major player, HIF1α, is regulated at different levels by various factors, including the transcription factor ELK3. The molecular mechanisms of this intimate connection remain largely unknown. Whilst investigating global ELK3-chromatin interactions, we uncovered an unexpected connection that involves the microRNA hsa-miR-155-5p, a hypoxia-inducible oncomir that targets HIF1α. One of the ELK3 chromatin binding sites, detected by Chromatin Immuno-Precipitation Sequencing (ChIP-seq) of normal Human Umbilical Vein Endothelial Cells (HUVEC), is located at the transcription start site of the MIR155HG genes that expresses hsa-miR-155-5p. We confirmed that ELK3 binds to this promoter by ChIP and quantitative polymerase chain reaction (QPCR). We showed that ELK3 and hsa-miR-155-5p form a double-negative regulatory loop, in that ELK3 depletion induced hsa-miR-155-5p expression and hsa-miR-155-5p expression decreased ELK3 expression at the RNA level through a conserved target sequence in its 3'-UTR. We further showed that the activities of hsa-miR-155-5p and ELK3 are functionally linked. Pathway analysis indicates that both factors are implicated in related processes, including cancer and angiogenesis. Hsa-miR-155-5p expression and ELK3 depletion have similar effects on expression of known ELK3 target genes, and on in-vitro angiogenesis and wound closure. Bioinformatic analysis of cancer RNA-seq data shows that hsa-miR-155-5p and ELK3 expression are significantly anti-correlated, as would be expected from hsa-miR-155-5p targeting ELK3 RNA. Finally, hypoxia (0% oxygen) down-regulates ELK3 mRNA in a microRNA and hsa-miR-155-5p dependent manner. These results tie ELK3 into the hypoxia response pathway through an oncogenic microRNA and into a circuit implicated in the dynamics of the hypoxic response. This crosstalk could be important for the development of new treatments for a range of pathologies.