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Background: In the United States, rare disease (RD) is defined as a condition that affects fewer than 200,000 individuals. Collectively, RD affects an estimated 30 million Americans. A significant portion of RD has an underlying genetic cause; however, this may go undiagnosed. To better serve these patients, the Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD) was created under the auspices of the Center for Individualized Medicine (CIM) aiming to integrate genomics into subspecialty practice including targeted genetic testing, research, and education., Methods: Patients were identified by subspecialty healthcare providers from 11 clinical divisions/departments. Targeted multi-gene panels or custom exome/genome-based panels were utilized. To support the goals of PRaUD, a new clinical service model, the Genetic Testing and Counseling (GTAC) unit, was established to improve access and increase efficiency for genetic test facilitation. The GTAC unit includes genetic counselors, genetic counseling assistants, genetic nurses, and a medical geneticist. Patients receive abbreviated point-of-care genetic counseling and testing through a partnership with subspecialty providers., Results: Implementation of PRaUD began in 2018 and GTAC unit launched in 2020 to support program expansion. Currently, 29 RD clinical indications are included in 11 specialty divisions/departments with over 142 referring providers. To date, 1152 patients have been evaluated with an overall solved or likely solved rate of 17.5% and as high as 66.7% depending on the phenotype. Noteworthy, 42.7% of the solved or likely solved patients underwent changes in medical management and outcome based on genetic test results., Conclusion: Implementation of PRaUD and GTAC have enabled subspecialty practices advance expertise in RD where genetic counselors have not historically been embedded in practice. Democratizing access to genetic testing and counseling can broaden the reach of patients with RD and increase the diagnostic yield of such indications leading to better medical management as well as expanding research opportunities., (© 2023. The Author(s).)

Seawater was investigated as an alternative regenerant source to conventional salt-imported brine solutions in an anion exchange process treating surficial Florida coastal groundwater for the removal of sulfate and organics. Bench-scale column testing revealed that filtered Sarasota Bay seawater efficiently regenerated the anion resin media; however, sulfate exchange capacity decreased by 8.42% compared with conventional 10% salt regeneration methods. Addition of 3% sodium chloride increased regeneration efficiency, reduced exchange capacity losses to 2.4% as compared to conventional 10% salt regeneration methods. Regeneration resulted in 2.13 mg/L of bromide leakage; however, addition of 3% sodium chloride to seawater reduced bromide leakage to 1.25 mg/L. A correlation between bromide exchange and the regenerant chloride-to-bromide molar ratio (CBMR) was observed, yielding less bromide exchange at higher CBMRs. Bromide adsorption followed pseudo 2nd order kinetics and chemisorption was the rate controlling step. Increasing the CBMR of the regenerant was found to shift adsorption behaviour, allowing intra-particle diffusion to occur sooner. Bromide equilibrium appeared to follow a logarithmic decay as the CBMR of the regenerant increased. Intra-particle and film diffusion mechanisms were evaluated that indicated the presence of diffusion-based processes and more than one rate controlling step. An empirical function was derived to approximate bromide equilibrium adsorption in relation to a regenerant's CBMR. Seawater as a regenerant when enhanced with sodium chloride shows promise as an anion exchange regenerant; additionally, classification of a seawater regenerant's CBMR can provide insight into the kinetic and equilibrium relationships of bromide exchange.

Winter annual cover crops can be planted before soybean in Mississippi for many agronomic reasons. Incorporating winter annual cover crops into soybean production changes the seasonal hosts within fields. Some studies suggest that reducing tillage and using diverse species of cover crops can increase arthropod diversity and predator activity. Neonicotinoid seed treatments are often implemented to combat early season insect pests in soybean that follow cover crops, but negative effects on the environment such as reductions in biodiversity are often attributed to these compounds. We conducted an experiment to measure the effects on the diversity of the soybean epigeal and foliar communities when incorporating cover crops as well as insecticidal seed treatments into Mississippi soybean growing systems. Our results showed that legume cover crops had significant impacts on the epigeal community diversity of soybean planted behind them. These cover crops, especially hairy vetch, supported a more diverse foliar community before termination. To prevent increases in herbivorous arthropods, neonicotinoid seed treatments can be used without affecting epigeal predators such as beetles, ants, and spiders. The neonicotinoid seed treatments affected arthropod diversity, but the reductions were mainly caused by decreases in herbivorous pest insects that fed on treated soybean plants., (© The Author(s) 2022. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: General medical-surgical units struggle with how best to use cardiac monitor alarms to alert nursing staff to important abnormal heart rates (HRs) and rhythms while limiting inappropriate and unnecessary alarms that may undermine both patient safety and quality of care. When alarms are more often false than true, the nursing staff's sense of urgency in responding to alarms is diminished. In this syndrome of "clinical alarm fatigue," the simple burden of alarms desensitizes caregivers to alarms. Noise levels associated with frequent alarms may also heighten patient anxiety and disrupt their perception of a healing environment. Alarm fatigue experienced by nurses and patients is a significant problem and innovative solutions are needed., Objective: The purpose of this quality improvement study was to determine variables that would safely reduce noncritical telemetry and monitor alarms on a general medical-surgical unit where standard manufacturer defaults contributed to excessive audible alarms., Methods: Mining of alarm data and direct observations of staff's response to alarms were used to identify the self-reset warning alarms for bradycardia, tachycardia, and HR limits as the largest contributors of audible alarms. In this quality improvement study, the alarms for bradycardia, tachycardia, and HR limits were changed to "crisis," requiring nursing staff to view and act on the alarm each time it sounded. The limits for HR were HR low 45 bpm and HR high 130 bpm., Results: An overall 89% reduction in total mean weekly audible alarms was achieved on the pilot unit (t = 8.84; P < .0001) without requirement for additional resources or technology. Staff and patient satisfaction also improved. There were no adverse events related to missed cardiac monitoring events, and the incidence of code blues decreased by 50%., Conclusions: Alarms with self-reset capabilities may result in an excess number of audible alarms and clinical alarm fatigue. By eliminating self-resetting alarms, the volume of audible alarms and associated clinical alarm fatigue can be significantly reduced without requiring additional resources or technology or compromising patient safety and lead to improvement in both staff and patient satisfaction.

Patients presenting in acute congestive heart failure demonstrate severe dyspnea, rales, hypoxia, and chest radiograph findings of acute pulmonary vascular congestion. Not all patients, however, have systolic left ventricular dysfunction. While initial stabilization of an acute episode in decompensated heart failure may follow a common pathway, understanding the nature of the dysfunction is important in selecting both short-term and long-term pharmacologic interventions required in the patient's management.

A program has been developed in Boston to bring together hospital and industrial biomedical engineers, BMETs, CEs, nurses, physicians, the Massachusetts Medical Devices Society, academic engineering technologists, and students. This program is headquartered at the Center for Clinical Engineering at the Wentworth Institute of Technology, and is designed to serve and support the interests of the participants for educational, professional, networking and interdisciplinary activities. Because of the availability of engineering technology programs at Wentworth, and the willingness of local professionals to participate, a comprehensive and unique program has been developed to train BMETs and CEs. This program emphasizes hands-on electronic technology, biomedical lectures and laboratories, management lectures and in-hospital preceptorships under the supervision of BMETs, CEs, biomedical directors and nurses.

Six different freezing/thawing programs, which varied freezing rate, duration of freezing, and thawing rates, were used to investigate the effect of these factors on cell destruction in dog skin. The range of tissue temperatures produced was from -15 to -50 degrees C. The extent of destruction was evaluated by skin biopsies 3 days after cold injury. In single, short freezing/thawing cycles, the temperature reached in the tissue was the prime factor in cell death. Longer freezing time and slow thawing were also important lethal factors which increased destruction of cells. Cooling rate, whether slow or fast, made little difference in the outcome. The experiments suggested that present-day, commonly employed cryosurgical techniques, which feature fast cooling, slow thawing, and repetition of the freeze/thaw cycle, should be modified by the use of maintenance of the tissue in the frozen state for several minutes and slow thawing. Thawing should be complete before freezing is repeated. These modifications in technique will maximize tissue destruction, an important consideration in cancer cryosurgery.

Tissue temperature and impedance were measured in dog skin during freezing in situ. The previously frozen skin was removed by punch biopsies 3 days later to permit microscopic evaluation of the extent of necrosis. The histologic observations were related to the temperature and impedance measurements in an effort to determine the usefulness of the monitoring techniques in clinical cryosurgery. Tissue temperature and impedance have a definite relationship in tissue freezing, but the range of temperatures about any impedance values causes some concern. The tissue biopsies showed that an impedance value of at least 10 Mohms is not always associated with tissue death. In these experiments, there was the usual range of temperatures in relation to tissue death, but tissue temperatures of -30 degrees C and colder were always associated with complete necrosis. It is concluded that tissue temperatures are the more accurate and useful monitoring technique to supplement clinical judgment. However, impedance techniques may also be used to monitor therapy, especially if used primarily to monitor depth of therapy, and if controlled by clinical judgment wary of the inaccuracy of the technique.

To determine the relationship between hepatic glucose clearance and elevated epinephrine levels in sepsis, dogs with gangrenous cholecystitis were anesthetized and received either propranolol hydrochloride (mean dose, 0.29 mg/kg) or saline solution before intraduodenal glucose injection (2.5 g/kg). The amounts of glucose, insulin, and glucagon in the portal vein, the hepatic artery, and the hepatic vein were determined from the concentrations and the blood flows in these vessels over a two-hour period. Normal dogs served as controls. The amounts of glucose, insulin, and glucagon reaching the livers of both septic groups were the same. However, propranolol treatment increased the percent of glucose extracted by the liver without affecting the extractions of insulin or glucagon. Propranolol reverses the limitation of hepatic glucose extraction in sepsis by a direct effect. Whether the extracted glucose is utilizable as an energy substrate needs to be established.

The effect of temporary periods of ischemia on the electrolytes and water of myocardial cells were studied in groups of mongrel dogs. Myocardial tissue exposed to 40 minutes of ischemia induced by occlusion of the circumflex branch of the left coronary artery developed no changes in water or electrolytes when compared to nonischemic left ventricle of the same or sham-operated animals, even though this period of ischemia is known to produce irreversible injury to many of the damaged cells. However, reperfusion of the affected myocardium with arterial blood for only 2 minutes resulted in striking increases in tissue H(2)O, Na(-), Cl(-) and Ca(2-). These changes in electrolytes increased in severity with longer periods of reflow, and tissue K(+) was decreased significantly after 10 minutes of reflow had passed. Analysis of the results suggested that the tissue edema was primarily the result of cellular swelling. Myocardium exposed to 15 minutes of ischemia followed by 2 minutes of reflow showed no significant changes aside from a slight increase in Na(+). These studies demonstrate that defects in cell volume regulation occur early in severe ischemic injury.

Changes produced in the posterior papillary muscle of the dog following 40 minutes of circumflex artery occlusion and 0 to 20 minutes of blood reflow were studied by electron miroscopy. With no reflow of blood, myocardial cells were modestly swollen, contained amorphous matrix densities in the mitochondria, had aggregation and margination of nuclear chromatin and relaxation of myofibrils. With as little as 2 minutes of blood reflow, cells developed contraction bands and were greatly swollen due to a generalized increase in sarcoplasmic space, formation of vacuoles and swelling of mitochondria. Frequently, cell membranes were lifted away from the myofibers, forming large subsarcolemmal blebs which appeared capable of compressing adjacent capillaries. The extracellular space did not appear to be enlarged, and the marked tissue edema found after reflow was due primarily to accumulation of intracellular fluid. In addition to explosive cell swelling, there was, over the 2- to 20-minute period of reflow, a progressive increase in size and number of granular mitochondrial dense bodies of the calcium accumulation type. No significant changes in lysosomes were observed. The speed with which the morphologic changes developed during very early reflow periods suggests that irreversible ischemic injury produces a defect in cell volume regulation during the phase of ischemia and that this defect becomes manifest if arterial flow is restored to the affected cells.

Although glucose is regularly administered to patients after partial hepatic resection, its contribution to survival and/or liver regeneration is unclear. To examine this question fed and anesthetized rats underwent 68% or 90% hepatectomy and received either oral 20% glucose solution or tap water (controls) ad lib for 24 h. Survival was compared by life table analysis and the regeneration response measured by 3H-thymidine uptake into liver deoxyribonucleic acid (DNA). Profound hypoglycemia (60 +/- 8 mg/dl) following 90% hepatectomy in controls was corrected by glucose feeding (99 +/- 25 mg/dl) and survival was enhanced (75 +/- 0.09% vs. 42 +/- 0.1%, p less than 0.01). No deaths occurred in the 68% hepatectomy groups wherein untreated hypoglycemia was not as severe (106 +/- 6 mg/dl). However, after 68% hepatectomy glucose adversely affected the regeneration response. We conclude that glucose feeding corrected the life threatening hypoglycemia following 90% hepatectomy. Prophylactic glucose administration after 68% hepatectomy reduced the liver regeneration response. Selective glucose administration to prevent lethal hypoglycemia may provide optimal survival and conditions for regeneration.