Preventing Complications of Undiagnosed Diabetic Peripheral Neuropathy in Rural Healthcare Settings

Background: Diabetic peripheral neuropathy (DPN) affects the lives of approximately 50% of all persons diagnosed with diabetes. Patients who are minorities, residents of rural communities, low income, or non-compliant with treatment, have a higher risk of developing DPN. The long-term effects interfere with the patient’s abilities to carry out activities of daily living (ADLs) and instrumental activities of daily living (IADLs). Patients incur debt from medical expenses, depression from the inability to perform self- care, and became withdrawn because of their distorted body image. Purpose: The purpose of this project was to use the Michigan Neuropathy Screening Instrument (MNSI) scale to improve patient outcomes by promoting better identification of individuals who need to be referred out to a specialist. Design Methods: The patients were interviewed and surveyed using the Michigan Neuropathy Screening Instrument (MNSI). After using the MNSI tool, patients were evaluated for possible referral to podiatry and vascular specialty. Conclusion: Results demonstrated the use of the MNSI tool improves the screening process of patients diagnosed with diabetes reporting signs and symptoms of DPN. Implications for Nursing: This project has the potential to improve patient quantality of life, and lower cost to both patient and healthcare providers

Device management of arrhythmias after Fontan conversion

ObjectivesWe assessed our pacemaker strategy, use of antitachycardia therapies, generator longevity, and need for programming changes in patients having Fontan conversion with arrhythmia surgery.MethodsBetween 1994 and 2008, of 121 consecutive patients having Fontan conversion and arrhythmia surgeries, 120 patients underwent pacemaker implantation at the time of Fontan conversion (mean age 22.9 ± 8.1 years). Prior pacemakers were in place in 32/120 (26.7%) patients. Between 1994 and 1998, single-chamber atrial antitachycardia pacemakers were implanted (n = 12); atrial rate-responsive pacemakers (n = 31) were implanted between 1998 and 2002. Dual-chamber rate-responsive pacemakers (n = 16) were used between 2002 and 2003, and subsequently dual-chamber antitachycardia pacemakers (n = 61) have become the pacemaker of choice. Leads have evolved from transatrial endocardial leads to epicardial unipolar and subsequently bipolar leads.ResultsAmong 87 patients with adequate follow-up, all are currently atrially paced at a minimum lower rate ≥70 beats per minute. Single-chamber atrial pacemakers were implanted in 43 (antitachycardia in 12), and dual-chamber pacemakers in 77 (antitachycardia in 61); multisite ventricular leads were placed in 7 patients. Far-field R-wave sensing in 78.6% of unipolar atrial leads led to use of epicardial bipolar leads. Late atrioventricular block (24%) led to routine implantation of dual-chamber pacemakers. Antitachycardia pacing was utilized in 7%. One patient required acute lead revision and 4 required late upgrade to dual-chamber pacemakers. There was no pacemaker-related infection. Twenty patients required generator change, and the mean device longevity was 7.53 years.ConclusionsCustomized pacemaker therapy can optimize management of patients following Fontan conversion. Device longevity is excellent. Based on our experience with 120 Fontan conversions, we recommend placement of a dual-chamber antitachycardia pacemaker with bipolar steroid-eluting epicardial leads in all patients at the time of the conversion

A novel virulence strategy for Pseudomonas aeruginosa mediated by an autotransporter with arginine-specific aminopeptidase activity

The opportunistic human pathogen, Pseudomonas aeruginosa, is a major cause of infections in chronic wounds, burns and the lungs of cystic fibrosis patients. The P. aeruginosa genome encodes at least three proteins exhibiting the characteristic three domain structure of autotransporters, but much remains to be understood about the functions of these three proteins and their role in pathogenicity. Autotransporters are the largest family of secreted proteins in Gram-negative bacteria, and those characterised are virulence factors. Here, we demonstrate that the PA0328 autotransporter is a cell-surface tethered, arginine-specific aminopeptidase, and have defined its active site by site directed mutagenesis. Hence, we have assigned PA0328 with the name AaaA, for arginine-specific autotransporter of P. aeruginosa. We show that AaaA provides a fitness advantage in environments where the sole source of nitrogen is peptides with an aminoterminal arginine, and that this could be important for establishing an infection, as the lack of AaaA led to attenuation in a mouse chronic wound infection which correlated with lower levels of the cytokines TNFα, IL-1α, KC and COX-2. Consequently AaaA is an important virulence factor playing a significant role in the successful establishment of P. aeruginosa infections

Genome Rearrangements Detected by SNP Microarrays in Individuals with Intellectual Disability Referred with Possible Williams Syndrome

Intellectual disability (ID) affects 2-3% of the population and may occur with or without multiple congenital anomalies (MCA) or other medical conditions. Established genetic syndromes and visible chromosome abnormalities account for a substantial percentage of ID diagnoses, although for approximately 50% the molecular etiology is unknown. Individuals with features suggestive of various syndromes but lacking their associated genetic anomalies pose a formidable clinical challenge. With the advent of microarray techniques, submicroscopic genome alterations not associated with known syndromes are emerging as a significant cause of ID and MCA.High-density SNP microarrays were used to determine genome wide copy number in 42 individuals: 7 with confirmed alterations in the WS region but atypical clinical phenotypes, 31 with ID and/or MCA, and 4 controls. One individual from the first group had the most telomeric gene in the WS critical region deleted along with 2 Mb of flanking sequence. A second person had the classic WS deletion and a rearrangement on chromosome 5p within the Cri du Chat syndrome (OMIM:123450) region. Six individuals from the ID/MCA group had large rearrangements (3 deletions, 3 duplications), one of whom had a large inversion associated with a deletion that was not detected by the SNP arrays.Combining SNP microarray analyses and qPCR allowed us to clone and sequence 21 deletion breakpoints in individuals with atypical deletions in the WS region and/or ID or MCA. Comparison of these breakpoints to databases of genomic variation revealed that 52% occurred in regions harboring structural variants in the general population. For two probands the genomic alterations were flanked by segmental duplications, which frequently mediate recurrent genome rearrangements; these may represent new genomic disorders. While SNP arrays and related technologies can identify potentially pathogenic deletions and duplications, obtaining sequence information from the breakpoints frequently provides additional information

How Low Can You Go?: Widespread Challenges in Measuring Low Stream Discharge and a Path Forward

Low flows pose unique challenges for accurately quantifying streamflow. Current field methods are not optimized to measure these conditions, which in turn, limits research and management. In this essay, we argue that the lack of methods for measuring low streamflow is a fundamental challenge that must be addressed to ensure sustainable water management now and into the future, particularly as climate change shifts more streams to increasingly frequent low flows. We demonstrate the pervasive challenge of measuring low flows, present a decision support tool (DST) for navigating best practices in measuring low flows, and highlight important method developmental needs

Population turnover in remote oceania shortly after initial settlement

Ancient DNA from Vanuatu and Tonga dating to about 2,900–2,600 years ago (before present, BP) has revealed that the “First Remote Oceanians” associated with the Lapita archaeological culture were directly descended from the population that, beginning around 5000 BP, spread Austronesian languages from Taiwan to the Philippines, western Melanesia, and eventually Remote Oceania. Thus, ancestors of the First Remote Oceanians must have passed by the Papuan-ancestry populations they encountered in New Guinea, the Bismarck Archipelago, and the Solomon Islands with minimal admixture [1]. However, all present-day populations in Near and Remote Oceania harbor >25% Papuan ancestry, implying that additional eastward migration must have occurred. We generated genome-wide data for 14 ancient individuals from Efate and Epi Islands in Vanuatu from 2900–150 BP, as well as 185 present-day individuals from 18 islands. We find that people of almost entirely Papuan ancestry arrived in Vanuatu by around 2300 BP, most likely reflecting migrations a few hundred years earlier at the end of the Lapita period, when there is also evidence of changes in skeletal morphology and cessation of long-distance trade between Near and Remote Oceania [2, 3]. Papuan ancestry was subsequently diluted through admixture but remains at least 80%–90% in most islands. Through a fine-grained analysis of ancestry profiles, we show that the Papuan ancestry in Vanuatu derives from the Bismarck Archipelago rather than the geographically closer Solomon Islands. However, the Papuan ancestry in Polynesia—the most remote Pacific islands—derives from different sources, documenting a third stream of migration from Near to Remote Oceania

Trends in surgical aortic valve replacement in pre- and post-transcatheter aortic valve replacement eras at a structural heart center

BackgroundThe advent of transcatheter aortic valve replacement (TAVR) has directly impacted the lifelong management of patients with aortic valve disease. The U.S. Food and Drug Administration has approved TAVR for all surgical risk: prohibitive (2011), high (2012), intermediate (2016), and low (2019). Since then, TAVR volumes are increasing and surgical aortic valve replacements (SAVR) are decreasing. This study sought to evaluate trends in isolated SAVR in the pre- and post-TAVR eras.MethodsFrom January 2000 to June 2020, 3,861 isolated SAVRs were performed at a single academic quaternary care institution which participated in the early trials of TAVR beginning in 2007. A formal structural heart center was established in 2012 when TAVR became commercially available. Patients were divided into the pre-TAVR era (2000–2011, n = 2,426) and post-TAVR era (2012–2020, n = 1,435). Data from the institutional Society of Thoracic Surgeons National Database was analyzed.ResultsThe median age was 66 years, similar between groups. The post-TAVR group had a statistically higher rate of diabetes, hypertension, dyslipidemia, heart failure, more reoperative SAVR, and lower STS Predicted Risk of Mortality (PROM) (2.0% vs. 2.5%, p < 0.0001). There were more urgent/emergent/salvage SAVRs (38% vs. 24%) and fewer elective SAVRs (63% vs. 76%), (p < 0.0001) in the post-TAVR group. More bioprosthetic valves were implanted in the post-TAVR group (85% vs. 74%, p < 0.0001). Larger aortic valves were implanted (25 vs. 23 mm, p < 0.0001) and more annular enlargements were performed (5.9% vs. 1.6%, p < 0.0001) in the post-TAVR era. Postoperatively, the post-TAVR group had less blood product transfusion (49% vs. 58%, p < 0.0001), renal failure (1.4% vs. 4.3%, p < 0.0001), pneumonia (2.3% vs. 3.8%, p = 0.01), shorter lengths of stay, and lower in-hospital mortality (1.5% vs. 3.3%, p = 0.0007).ConclusionThe approval of TAVR changed the landscape of aortic valve disease management. At a quaternary academic cardiac surgery center with a well-established structural heart program, patients undergoing isolated SAVR in the post-TAVR era had lower STS PROM, more implantation of bioprosthetic valves, utilization of larger valves, annular enlargement, and lower in-hospital mortality. Isolated SAVR continues to be performed in the TAVR era with excellent outcomes. SAVR remains an essential tool in the lifetime management of aortic valve disease

ehealth technology in cardiac exercise therapeutics for pediatric patients with congenital and acquired heart conditions: a summary of evidence and future directions

Many children and adolescents with congenital and acquired heart disease (CHD) are physically inactive and participate in an insufficient amount of moderate-to-vigorous intensity exercise. Although physical activity (PA) and exercise interventions are effective at improving short- and long-term physiological and psychosocial outcomes in youth with CHD, several barriers including resource limitations, financial costs, and knowledge inhibit widespread implementation and dissemination of these beneficial programs. New and developing eHealth, mHealth, and remote monitoring technologies offer a potentially transformative and cost-effective solution to increase access to PA and exercise programs for youth with CHD, yet little has been written on this topic. In this review, a cardiac exercise therapeutics (CET) model is presented as a systematic approach to PA and exercise, with assessment and testing guiding three sequential PA and exercise intervention approaches of progressive intensity and resource requirements: (1) PA and exercise promotion within a clinical setting; (2) unsupervised exercise prescription; and (3) medically supervised fitness training intervention (i.e., cardiac rehabilitation). Using the CET model, the goal of this review is to summarize the current evidence describing the application of novel technologies within CET in populations of children and adolescents with CHD and introduce potential future applications of these technologies with an emphasis on improving equity and access to patients in low-resource settings and underserved communities

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Determining Spatial Distribution and Physical Properties of the Vashon Advance Outwash near Mountlake Terrace, Washington

This study is aimed at determining the spatial distribution, physical properties, and groundwater conditions of the Vashon advance outwash (Qva) in the Mountlake Terrace, WA area. The Qva is correlative with the Esperance Sand, as defined at its type section; however, local variations in the Qva are not well-characterized (Mullineaux, 1965). While the Qva is a dense glacial unit with low compressibility and high frictional shear strength (Gurtowski and Boirum, 1989), the strength of this unit can be reduced when it becomes saturated (Tubbs, 1974). This can lead to caving or flowing in excavations, and on a larger scale, can lead to slope failures and mass-wasting when intersected by steep slopes. By studying the Qva, we can better predict how it will behave under certain conditions, which will be beneficial to geologists, hydrogeologists, engineers, and environmental scientists during site assessments and early phases of project planning. In this study, I use data from 27 geotechnical borings from previous field investigations and C-Tech Corporation’s EnterVol software to create three-dimensional models of the subsurface geology in the study area. These models made it possible to visualize the spatial distribution of the Qva in relation to other geologic units. I also conducted a comparative study between data from the borings and generalized published data on the spatial distribution, relative density, soil classification, grain-size distribution, moisture content, groundwater conditions, and aquifer properties of the Qva. I found that the elevation of the top of the Qva ranges from 247 to 477 ft. I found that the Qva is thickest where the modern topography is high, and is thinnest where the topography is low. The thickness of the Qva ranges from absent to 242 ft. Along the northern, east-west trending transect, the Qva thins to the east as it rises above a ridge composed of Pre- Vashon glacial deposits. Along the southern, east-west trending transect, the Qva pinches out against a ridge composed of pre-Vashon interglacial deposits. Two plausible explanations for this ridge are paleotopography and active faulting associated with the Southern Whidbey Fault Zone. Further investigations should be done using geophysical methods and the modeling methods described in this study to determine the nature of this ridge. The relative density of the Qva in the study area ranges from loose to very dense, with the loose end of the spectrum probably relating to heave in saturated sands. I found subtle correlations between density and depth. Volumetric analysis of the soil groups listed in the boring logs indicate that the Qva in the study area is composed of approximately 9.5% gravel, 89.3% sand, and 1.2% silt and clay. The natural moisture content ranges from 3.0 to 35.4% in select samples from the Qva. The moisture content appears to increase with depth and fines content. The water table in the study area ranges in elevation from 231.9 to 458 ft, based on observations and measurements recorded in the boring logs. The results from rising-head and falling-head slug tests done at a single well in the study area indicate that the geometric mean of hydraulic conductivity is 15.93 ft/d (5.62 x 10-03 cm/s), the storativity is 3.28x10-03, and the estimated transmissivity is 738.58 ft2/d in the vicinity of this observation well. At this location, there was 1.73 ft of seasonal variation in groundwater elevation between August 2014 and March 2015