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Emergency preparedness initiatives are a Medicare condition of participation in home healthcare, yet limited evidence on the impact of associated programming is available. The purpose of this exploratory pilot study was to examine the outcomes of an individualized emergency preparedness educational program provided by a physical therapist (PT) in the homes of older adults. The investigators recruited older adults (n = 30) using convenience sampling. An emergency preparedness education module was developed. Demographics, functional and environmental outcome measures, a pre- and post-education confidence survey, and learning outcomes were ascertained and analyzed. Participants reported being female (n = 23), 70 to 79 years (n = 15), and 19 individuals reported 35 different lifetime emergency events. Hearing and vision impairments, inability to change a battery or navigate stairs, and environmental deficits including clutter and poor lighting were identified. Closing bedroom doors at nighttime, functioning carbon monoxide and smoke detectors, creating an evacuation plan, and assembling first aid kits were learning outcomes. Trends toward increased confidence were identified, with statistically significant improvements in the ability to respond to a fire (P = .01), a heat wave (P = .03), and to crawl on hands and knees (P = .05) identified. This study provides emerging evidence that PTs have a role in improving an older adult's confidence to prepare for and respond to an emergency event.
Subject(s)
Home Care Services , Humans , Female , Aged , Male , Pilot Projects , Civil Defense/education , United States , Disaster PlanningABSTRACT
OBJECTIVE: To compare the immunogenicity, safety, and efficacy of Gan & Lee insulin glargine (GL Glargine) with that of the originator insulin glargine (Lantus) in patients with type 1 diabetes mellitus (T1DM). METHODS: This was a phase 3, multicenter, randomized, open-label, equivalence study. Five hundred seventy-six subjects with T1DM were randomized 1:1 to receive either GL Glargine or Lantus treatment for 26 weeks. The primary end point was the percentage of subjects in each treatment group who developed treatment-induced anti-insulin antibody after baseline and up to visit week 26, which was evaluated using a country-adjusted logistic regression model. The study also compared the changes in glycated hemoglobin, and adverse events including hypoglycemia. RESULTS: The percentage of subjects positive for treatment-induced anti-insulin antibody by Week 26 was 25.8% in the GL Glargine treatment group and 25.3% in the Lantus treatment group, with a 90% confidence interval (-5.4, 6.5) of the difference in proportions that fell completely between the similarity margins (-11.3, 11.3). The least squares mean difference between treatment groups for changes in glycated hemoglobin was -0.08 (90% confidence interval: -0.23, 0.06), and the other immunogenicity and safety profiles were comparable. CONCLUSION: GL Glargine demonstrated similar immunogenicity, efficacy, and safety compared to Lantus over 26 weeks in patients with T1DM.
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AIM: To evaluate the equivalence of immunogenicity, safety and efficacy of Gan & Lee (GL) Glargine (Basalin®; Gan & Lee Pharmaceutical) with that of the reference product (Lantus®) in adult participants with type 2 diabetes mellitus. METHODS: This was a phase 3, multicenter, open-label, equivalence trial conducted across 57 sites. In total, 567 participants with type 2 diabetes mellitus were randomized in a 1:1 ratio to undergo treatment with either GL Glargine or Lantus® for 26 weeks. The primary endpoint was the proportion of participants in each treatment arm who manifested treatment-induced anti-insulin antibodies (AIA). Secondary endpoints included efficacy and safety metrics, changes in glycated haemoglobin levels, and a comparative assessment of adverse events. Results were analysed using an equivalence test comparing the limits of the 90% confidence interval (CI) for treatment-induced AIA development to the prespecified margins. RESULTS: The percentages of participants positive for treatment-induced glycated haemoglobin by week 26 were similar between the GL Glargine (19.2%) and Lantus® (21.3%) treatment groups, with a treatment difference of -2.1 percentage points and a 90% CI (-7.6%, 3.5%) (predefined similarity margins: -10.7%, 10.7%). The difference in glycated haemoglobin was -0.08% (90% CI, -0.23, 0.06). The overall percentage of participants with any treatment-emergent adverse events was similar between the GL Glargine (80.1%) and Lantus® (81.6%) treatment groups. CONCLUSIONS: GL Glargine was similar to Lantus® in terms of immunogenicity, efficacy, and safety, based on the current study.
Subject(s)
Biosimilar Pharmaceuticals , Diabetes Mellitus, Type 2 , Glycated Hemoglobin , Hypoglycemic Agents , Insulin Glargine , Adult , Aged , Female , Humans , Male , Middle Aged , Biosimilar Pharmaceuticals/therapeutic use , Biosimilar Pharmaceuticals/adverse effects , Blood Glucose/drug effects , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/immunology , Glycated Hemoglobin/drug effects , Glycated Hemoglobin/metabolism , Glycated Hemoglobin/analysis , Hypoglycemia/chemically induced , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/adverse effects , Insulin Antibodies/blood , Insulin Glargine/therapeutic use , Insulin Glargine/adverse effects , Therapeutic Equivalency , Treatment OutcomeABSTRACT
The goal of palliative care is to focus on the holistic needs of the patient and their family versus the pathology of the patient's diagnosis to reduce the stress of illness. U.S. servicemembers deployed to austere environments worldwide have significantly less access to palliative care than in military treatment facilities in the U.S. Preparation for future conflicts introduces the concept of prolonged medical management for an environment where urgent casualty evacuation is impossible. Ketamine is currently widely used for analgesia and anesthesia in the care of military service members and its use has increased in combat zones of Iraq and Afghanistan due to the favorable preservation of respiratory function, minimal changes in hemodynamics, and lower pain scores compared to opioids. Ketamine acts as a non-competitive antagonist on N-methyl-D aspartate (NMDA) receptors. Its anesthesia and analgesic effects are complex and include both presynaptic and postsynaptic neurons in brain and spinal cord. The use of palliative care to minimize suffering should not be withheld due to the logistical boundaries of austere military environments or lack of guidelines for recommended use. The use of ketamine for palliative care is a new clinical management strategy to provide both sedation and pain management for an acute pain crisis or comfort measures for the terminally ill. This makes ketamine an attractive consideration for palliative care when managing critically wounded patients for an extended time.
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Light is a critical component of indoor plant cultivation, as different wavelengths can influence both the physiology and morphology of plants. Furthermore, fertilization and seeding density can also potentially interact with the light recipe to affect production outcomes. However, maximizing production is an ongoing research topic, and it is often divested from resource use efficiencies. In this study, three species of microgreens-kohlrabi; mustard; and radish-were grown under five light recipes; with and without fertilizer; and at two seeding densities. We found that the different light recipes had significant effects on biomass accumulation. More specifically, we found that Far-Red light was significantly positively associated with biomass accumulation, as well as improvements in height, leaf area, and leaf weight. We also found a less strong but positive correlation with increasing amounts of Green light and biomass. Red light was negatively associated with biomass accumulation, and Blue light showed a concave downward response. We found that fertilizer improved biomass by a factor of 1.60 across species and that using a high seeding density was 37% more spatially productive. Overall, we found that it was primarily the main effects that explained microgreen production variation, and there were very few instances of significant interactions between light recipe, fertilization, and seeding density. To contextualize the cost of producing these microgreens, we also measured resource use efficiencies and found that the cheaper 24-volt LEDs at a high seeding density with fertilizer were the most efficient production environment for biomass. Therefore, this study has shown that, even with a short growing period of only four days, there was a significant influence of light recipe, fertilization, and seeding density that can change morphology, biomass accumulation, and resource input costs.
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Biocatalysis has become a major driver in the innovation of preparative chemistry. Enzyme discovery, engineering and computational design have matured to reliable strategies in the development of biocatalytic processes. By comparison, substrate engineering has received much less attention. In this Minireview, we highlight the idea that the design of synthetic reagents may be an equally fruitful and complementary approach to develop novel enzyme-catalysed group transfer chemistry. This Minireview discusses key examples from the literature that illustrate how synthetic substrates can be devised to improve the efficiency, scalability and sustainability, as well as the scope of such reactions. We also provide an opinion as to how this concept might be further developed in the future, aspiring to replicate the evolutionary success story of natural group transfer reagents, such as adenosine triphosphate (ATP) and S-adenosyl methionine (SAM).
Subject(s)
BiocatalysisABSTRACT
Black people represent less than 13% of the population in the United States, but over 15% of COVID-19 deaths, with a mortality rate two times higher than White people. The Black Church system has historically been in a unique position to serve Black communities, particularly during times of crisis. The deep-rooted connection of the Black Church system within Black communities was largely shaped by slavery and segregation. However, there have been questions about the relevance of the Black Church system today. The objective of this commentary is to describe the intersectionality of ministry and health that has been illuminated in a profound way during this pandemic. Those in leadership had to evaluate and disseminate COVID-19 information to congregants, recognizing mistrust of the medical and public health systems still permeates throughout Black communities. Moreover, the death of George Floyd sparked international outcry, which launched church leaders to respond to a second pandemic: systemic racism. Understanding ways the Black Church responded to COVID-19, and systemic racism, is significantly important to public health and medical communities as it addresses the relevance of this system and ways to appropriately support during another public health crisis.
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BACKGROUND: Povidone-iodide (Betadine) is an antiseptic that is applied topically and has many uses in the medical community, such as in wound care and pre- and post-operative surgical procedures. This study was done to measure the effectiveness of Betadine solutions in inhibiting the growth of Gram-negative and Gram-positive bacteria. METHODS: The ability of 2.5 and 10% Betadine solutions to inhibit bacterial growth was measured against Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Acinetobacter baumannii. We grew the bacteria independently and together to simulate a hospital environment. RESULTS: All the bacteria showed zones of inhibition. However, discs were also tested for live bacteria using the colony-forming unit assay. Complete killing was only seen for S. aureus with the 10% Betadine solution. All other bacteria showed growth on the disc. CONCLUSIONS: This study showed several things. First, the zone of inhibition assay does not give an accurate assessment of antimicrobial properties when used alone and should be followed by a colony-forming unit assay. Second, 2.5% and 5% Betadine do not have effective antimicrobial properties against any of the bacteria tested, and 10% Betadine is only effective against S. aureus and not effective against the other bacteria tested.
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Selenium covalently bonded to cellulose can catalyze the formation of superoxide radicals. Candida albicans, colonizes epithelial surfaces and can be a fatal infection in immunocompromised people. In this study, we demonstrated the ability of organo-selenium, covalently attached to cotton textile dressings to kill C. albicans biofilms.
Subject(s)
Candida albicans , Selenium , Humans , Selenium/pharmacology , Cellulose/pharmacology , Polymers , Antifungal Agents/pharmacology , Biofilms , BandagesABSTRACT
This retrospective review examines clozapine's effects on treatment-refractory incarcerated individuals (N = 23) with recurrent thoughts of self-harm and/or self-injurious behavior. Emergent suicide risk assessments and days on suicide watch were assessed for the 3 months pre- and post-clozapine treatment. Total suicide assessments fell from 73 pre- to 14 post-clozapine, with a median of 2 assessments (interquartile range [IQR]: 1,5) pre-clozapine compared with 0 (IQR: 0,1) post-clozapine (p < 0.0001). Total days on suicide watch decreased from 104 days pre- to 32 post-clozapine, with a median of 3 days (IQR: 0,9) pre-clozapine compared with 0 (IQR: 0,0) post-clozapine (p = 0.0012). Emergency room visits and medical hospitalizations decreased substantially for all months of treatment. Clozapine treatment was associated with marked reductions in self-injurious thoughts and behaviors in high-risk incarcerated individuals.
Subject(s)
Clozapine , Prisoners , Self-Injurious Behavior , Suicide , Humans , Clozapine/therapeutic use , Suicidal Ideation , Self-Injurious Behavior/drug therapy , Self-Injurious Behavior/epidemiologyABSTRACT
The non-medical use of opioids has become a national crisis in the USA. Developing non-opioid pharmacotherapies for controlling this opioid epidemic is urgent. Dopamine D3 receptor (D3R) antagonists and low efficacy partial agonists have shown promising profiles in animal models of opioid use disorders (OUD). However, to date, advancement to human studies has been limited. Here we report the effects of (S)- and (R)-enantiomers of (±)-ABS01-113, structural analogs of the D3R partial agonist, (±)-VK4-40, in which the 3-OH in the linking chain is replaced by 3-F group. (S)- and (R)-ABS01-113 are identical in chemical structure but with opposite chirality. In vitro receptor binding and functional assays indicate that (S)-ABS01-113 is an efficacious (55%) and potent (EC50 = 7.6 ± 3.9 nM) D3R partial agonist, while the (R)-enantiomer is a potent D3R antagonist (IC50 = 11.4 nM). Both (S)- and (R)-ABS01-113 bind with high affinity to D3R (Ki = 0.84 ± 0.16 and 0.37 ± 0.06 nM, respectively); however, the (S)-enantiomer is more D3/D2-selective (>1000-fold). Pharmacokinetic analyses indicate that both enantiomers display excellent oral bioavailability and high brain penetration. Systemic administration of (S)- or (R)-ABS01-113 alone failed to alter open-field locomotion in male rats and mice. Interestingly, pretreatment with (S)- or (R)-ABS01-113 attenuated heroin-enhanced hyperactivity, heroin self-administration, and (heroin + cue)-induced reinstatement of drug-seeking behavior. Together, these findings reveal that both enantiomers, particularly the highly selective and efficacious D3R partial agonist (S)-ABS01-113, demonstrate promising translational potential for the treatment of OUD.
Subject(s)
Opioid-Related Disorders , Receptors, Dopamine D3 , Animals , Rats , Male , Mice , Humans , Receptors, Dopamine D3/metabolism , Heroin , Dopamine Antagonists/pharmacology , Drug-Seeking Behavior , Analgesics, Opioid/pharmacology , Dopamine Agonists/pharmacologyABSTRACT
OBJECTIVE: Dental plaque is a complex structure (called a biofilm) that is produced by a community of oral bacteria. As microorganisms accumulate in the oral cavity, bacteria can assemble into biofilms that protect them from antibiotics and disinfectants, which contribute to dental cavities and oral infections that acts as the seed for further infections throughout the body. Therefore, there is great interest in developing dental sealants that can effectively eliminate biofilms formed from an assortment of oral bacteria species. METHODS: In previous papers, it was shown that both in vivo and in vitro use of organo-selenium dental sealants have the potential to be an effective method for preventing dental caries and plaque formation. However, our previous in vitro study only examined the effect of the organo-selenium sealants on Streptococcus mutans and salivarius. Since that time, this organo-selenium sealant has been changed to improve its curing time. RESULTS: We showed a selenium containing sealant (SeLECT-DefenseTM) can completely eliminate biofilm formation on the sealant at selenium concentrations of 0.25% and higher, by S. salivarius, S. sanguinis, or S. mutans, individually or in combination. This selenium containing sealant can also completely inhibit the same bacteria from growing under the sealant, while control sealant cannot. The selenium containing sealant was tested for stability and it was found to still kill these same bacteria after soaking for the equivalent of one year in PBS (pH 7.4). It was also found that the combination of the three bacteria were also killed by the selenium sealant, thus ruling out potential synergism of the bacteria in forming resistance. SIGNIFICANCE: The following study showed that this modified selenium dental sealant effectively eliminates species of bacteria both on and under the dental sealant.
Subject(s)
Dental Caries , Selenium , Biofilms , Dental Caries/microbiology , Dental Caries/prevention & control , Humans , Pit and Fissure Sealants/pharmacology , Selenium/pharmacology , Streptococcus mutansABSTRACT
Background: Standard insulin infusion sets (IISs) are to be replaced every 2 to 3 days to avoid complications and diabetic ketosis due to set failure. This pivotal trial evaluated the safety and performance of a new extended-wear infusion set (EIS) when used for 7 days by adults with type 1 diabetes (T1D). Methods: This single-arm, nonrandomized trial enrolled adults (18-80 years of age) with T1D, who used their own MiniMed™ 670G system with insulin lispro or insulin aspart and the EIS for up to 7 days, across 12 consecutive wears. Safety endpoints included incidence of serious adverse events (SAEs), serious adverse device effects (SADEs), unanticipated adverse device effects (UADEs), severe hypoglycemia (SevHypo), severe hyperglycemia (SevHyper), diabetic ketoacidosis (DKA), and skin infection. The EIS failure rate due to unexplained hyperglycemia (i.e., suspected occlusion), the overall EIS survival rate, glycemic control outcomes (i.e., A1C, mean sensor glucose and time spent in established glucose ranges), total daily insulin delivered, and satisfaction with the EIS were determined. Results: The intention to treat population (n = 259, 48% men, 45.0 ± 14.1 years) wore a total of 3041 EIS devices. No SADE, UADE, or DKA events was reported. Overall rates of SAEs, SevHypo, SevHyper, and skin infection were 3.8, 2.5, 104.1, and 20.1 events per 100 participant-years. The rate of EIS failure due to unexplained hyperglycemia at the end of day 7 was 0.1% (95% confidence interval [CI]: 0.03-0.51) and 0.4% (95% CI: 0.16-1.00) for insulin lispro and aspart use, respectively. Overall EIS survival rate at the end of day 7 was 77.8% (95% CI: 76.2-79.3), glycemic control did not change, and participants reported greater satisfaction with the EIS compared with standard IISs worn before the study (P < 0.001). Conclusions: This investigation demonstrates that the EIS, when worn for up to 7 days, was safe and rated with high satisfaction, without adversely affecting glycemic control in adults with T1D. Clinical Trial Registration number: NCT04113694 (https://clinicaltrials.gov/ct2/show/NCT04113694).
Subject(s)
Diabetes Mellitus, Type 1 , Diabetic Ketoacidosis , Hyperglycemia , Hypoglycemia , Adult , Blood Glucose , Diabetes Mellitus, Type 1/drug therapy , Diabetic Ketoacidosis/chemically induced , Female , Humans , Hyperglycemia/chemically induced , Hypoglycemia/chemically induced , Hypoglycemia/drug therapy , Hypoglycemia/prevention & control , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Insulin Infusion Systems , Insulin Lispro/therapeutic use , Male , Survival RateABSTRACT
Ubc13-catalyzed K63 ubiquitination is a major control point for immune signaling. Recent evidence has shown that the control of multiple immune functions, including chronic inflammation, pathogen responses, lymphocyte activation, and regulatory signaling, is altered by K63 ubiquitination. In this review, we detail the novel cellular sensors that are dependent on K63 ubiquitination for their function in the immune signaling network. Many pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can target K63 ubiquitination to inhibit pathogen immune responses; we describe novel details of the pathways involved and summarize recent clinically relevant SARS-CoV-2-specific responses. We also discuss recent evidence that regulatory T cell (Treg) versus T helper (TH) 1 and TH17 cell subset regulation might involve K63 ubiquitination. Knowledge gaps that merit future investigation and clinically relevant pathways are also addressed.
Subject(s)
COVID-19 , Lysine , Humans , Lysine/metabolism , SARS-CoV-2 , Signal Transduction , Ubiquitin-Protein Ligases/metabolism , UbiquitinationABSTRACT
Introduction: This trial assessed safety and effectiveness of an advanced hybrid closed-loop (AHCL) system with automated basal (Auto Basal) and automated bolus correction (Auto Correction) in adolescents and adults with type 1 diabetes (T1D). Materials and Methods: This multicenter single-arm study involved an intent-to-treat population of 157 individuals (39 adolescents aged 14-21 years and 118 adults aged ≥22-75 years) with T1D. Study participants used the MiniMed™ AHCL system during a baseline run-in period in which sensor-augmented pump +/- predictive low glucose management or Auto Basal was enabled for â¼14 days. Thereafter, Auto Basal and Auto Correction were enabled for a study phase (â¼90 days), with glucose target set to 100 or 120 mg/dL for â¼45 days, followed by the other target for â¼45 days. Study endpoints included safety events and change in mean A1C, time in range (TIR, 70-180 mg/dL) and time below range (TBR, <70 mg/dL). Run-in and study phase values were compared using Wilcoxon signed-rank test or paired t-test. Results: Overall group time spent in closed loop averaged 94.9% ± 5.4% and involved only 1.2 ± 0.8 exits per week. Compared with run-in, AHCL reduced A1C from 7.5% ± 0.8% to 7.0% ± 0.5% (<0.001, Wilcoxon signed-rank test, n = 155), TIR increased from 68.8% ± 10.5% to 74.5% ± 6.9% (<0.001, Wilcoxon signed-rank test), and TBR reduced from 3.3% ± 2.9% to 2.3% ± 1.7% (<0.001, Wilcoxon signed-rank test). Similar benefits to glycemia were observed for each age group and were more pronounced for the nighttime (12 AM-6 AM). The 100 mg/dL target increased TIR to 75.4% (n = 155), which was further optimized at a lower active insulin time (AIT) setting (i.e., 2 h), without increasing TBR. There were no severe hypoglycemic or diabetic ketoacidosis events during the study phase. Conclusions: These findings show that the MiniMed AHCL system is safe and allows for achievement of recommended glycemic targets in adolescents and adults with T1D. Adjustments in target and AIT settings may further optimize glycemia and improve user experience. Clinical Trial Registration number: NCT03959423.
Subject(s)
Diabetes Mellitus, Type 1 , Adolescent , Adult , Aged , Blood Glucose , Blood Glucose Self-Monitoring , Diabetes Mellitus, Type 1/drug therapy , Humans , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Insulin Infusion Systems , Middle Aged , Young AdultABSTRACT
Development of complications in type 1 diabetes patients can be reduced by modifying risk factors. We used a cross-sectional cohort of 1646 patients diagnosed with type 1 diabetes (T1D) to develop a clinical risk score for diabetic peripheral neuropathy (DPN), autonomic neuropathy (AN), retinopathy (DR), and nephropathy (DN). Of these patients, 199 (12.1%) had DPN, 63 (3.8%) had AN, 244 (14.9%) had DR, and 88 (5.4%) had DN. We selected five variables to include in each of the four microvascular complications risk models: age, age of T1D diagnosis, duration of T1D, and average systolic blood pressure and HbA1C over the last three clinic visits. These variables were selected for their strong evidence of association with diabetic complications in the literature and because they are modifiable risk factors. We found the optimism-corrected R2 and Harrell's C statistic were 0.39 and 0.87 for DPN, 0.24 and 0.86 for AN, 0.49 and 0.91 for DR, and 0.22 and 0.83 for DN, respectively. This tool was built to help inform patients of their current risk of microvascular complications and to motivate patients to control their HbA1c and systolic blood pressure in order to reduce their risk of these complications.
Subject(s)
Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Diabetic Neuropathies , Diabetic Retinopathy , Cross-Sectional Studies , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/epidemiology , Diabetic Neuropathies/epidemiology , Diabetic Retinopathy/epidemiology , Humans , Risk FactorsABSTRACT
This study examined the effect of clozapine on time assigned to restrictive housing (RH; i.e., solitary confinement), disciplinary infractions, and assaults on custody staff among patients treated within the North Carolina prison system. Records were reviewed for patients initiated on clozapine (n = 84) over a 3.5-year period. Fifty-nine patients completed at least three consecutive months of treatment and were included in data analysis. Assigned RH days and disciplinary infractions were assessed for the periods prior to and after treatment with clozapine. Patients accumulated 13,500 RH days pretreatment and 3,560 days postclozapine initiation. There was a significant reduction in RH days with clozapine treatment (P < .05). Patients with personality disorders (n = 36) had a significant decrease in RH days (P < .05), while those with psychotic disorders (n = 23) showed a decrease with borderline significance (P = .051). There were 253 disciplinary infractions pretreatment, including 27 assaults on custody staff, and 118 infractions posttreatment, including 7 assaults; the decrease in infractions was significant in the first three months of treatment (P < .05). The mean ± SD duration of treatment was 269 ± 102 days. Expanding clozapine use in state prisons should be a high priority, as these data are consistent with reports of clozapine's benefits in community settings.
Subject(s)
Antipsychotic Agents , Clozapine , Psychotic Disorders , Antipsychotic Agents/therapeutic use , Clozapine/therapeutic use , Housing , Humans , Personality Disorders , Prisons , Psychotic Disorders/drug therapyABSTRACT
Haemosporidian parasites may impact avian health and are subject to shifts in distribution and abundance with changing ecologic conditions. Therefore, understanding variation in parasite prevalence is important for evaluating biologically meaningful changes in infection patterns and associated population level impacts. Previous research in western Alaska, US, indicated a possible increase in Leucocytozoon spp. infection between Emperor Geese (Anser canagicus) sampled in 1996 (<1%, n=134) and during 2011-12 (19.9%, 95% confidence interval [CI]: 3.0-36.8%, n=77); however, different detection methods were used for these estimates. Prior research in this same region identified a lack of Leucocytozoon spp. parasites (0%, n=117) in sympatrically breeding Cackling Geese (Branta hutchinsii minima) in 2011. We molecularly screened blood samples collected from sympatrically breeding Emperor and Cackling Geese in western Alaska during additional breeding seasons to better assess temporal and species-specific variation in the prevalence of blood parasites. We found similar prevalence estimates for Leucocytozoon spp. parasites in Emperor Goose blood samples collected in 1998 and 2014, suggesting consistent infection of Emperor Geese with blood parasites at these time points. Using samples from sympatric geese sampled during 2014, we found evidence for a higher incidence of parasites among Emperor Geese (20.3%, 95% CI: 11.8-32.7%) compared to Cackling Geese (3.6%, 95% CI: 1.1-11.0%), reinforcing the previous finding of species-specific differences in infection. Furthermore, we detected Leucocytozoon, Haemoproteus, and Plasmodium spp. blood parasites in unflighted goslings of both species, supporting the possible transmission of these parasites at western Alaska breeding grounds. Our results help to clarify that prevalence of Leucocytozoon spp. parasites have probably remained consistent among Emperor Geese breeding in western Alaska since the late 1990s and that this species may disproportionally harbor Leucocytozoon spp. compared to sympatrically breeding Cackling Geese.
Subject(s)
Bird Diseases , Haemosporida , Parasites , Alaska/epidemiology , Animals , Bird Diseases/parasitology , Geese , Haemosporida/genetics , PrevalenceABSTRACT
Emperor Geese (Anser canagicus) are iconic waterfowl endemic to Alaska and adjacent areas of northeastern Russia that are considered to be near threatened by the International Union for Conservation. This species has been identified as harboring diverse viruses and parasites which have, at times, been associated with disease in other avian taxa. To better assess if disease represents a vulnerability for Emperor Geese breeding on the Yukon-Kuskokwim Delta, Alaska, we evaluated if haemosporidian parasites were associated with decreased mass or survival among adult female nesting birds captured during 2006-2016. Through molecular analyses, we detected genetically diverse Leucocytozoon, Haemoproteus, and Plasmodium parasites in 28%, 1%, and 1% of 607 blood samples screened in triplicate, respectively. Using regression analysis, we found evidence for a small effect of Leucocytozoon infection on the mass of incubating adult female Emperor Geese. The estimated mass of infected individuals was approximately 43 g (95% CI: 20-67 g), or approximately 2%, less than uninfected birds when captured during the second half of incubation (days 11-25). We did not, however, find support for an effect of Leucocytozoon infection on survival of adult female nesting Emperor Geese using a multi-state hidden Markov framework to analyze mark-resight and recapture data. Using parasite mitochondrial DNA cytochrome b sequences, we identified 23 haplotypes among infected Emperor Geese. Leucocytozoon haplotypes clustered into three phylogenetically supported clades designated as 'L. simondi clade A', 'L. simondi clade B', and 'other Leucocytozoon'. We did not find evidence that parasites assigned to any of these clades were associated with differential mass measures among nesting adult female Emperor Geese. Collectively, our results provide negligible evidence for Leucocytozoon parasites as causing detrimental effects to adult female Emperor Geese breeding on the Yukon-Kuskokwim Delta.
ABSTRACT
Chronic low-grade inflammation is involved in the pathogenesis of type-1 diabetes (T1D) and its complications. In this cross-section study design, we investigated association between serum levels of soluble cytokine receptors with presence of peripheral neuropathy in 694 type-1 diabetes patients. Sex, age, blood pressure, smoking, alcohol intake, HbA1c and lipid profile, presence of DPN (peripheral and autonomic), retinopathy and nephropathy was obtained from patient's chart. Measurement of soluble cytokine receptors, markers of systemic and vascular inflammation was done using multiplex immunoassays. Serum levels were elevated in in DPN patients, independent of gender, age and duration of diabetes. Crude odds ratios were significantly associated with presence of DPN for 15/22 proteins. The Odds ratio (OR) remained unchanged for sTNFRI (1.72, p=0.00001), sTNFRII (1.45, p=0.0027), sIL2Rα (1.40, p=0.0023), IGFBP6 (1.51, p=0.0032) and CRP (1.47, p=0.0046) after adjusting for confounding variables, HbA1C, hypertension and dyslipidemia. Further we showed risk of DPN is associated with increase in serum levels of sTNFRI (OR=11.2, p<10), sIL2Rα (8.69, p<10-15), sNTFRII (4.8, p<10-8) and MMP2 (4.5, p<10-5). We combined the serum concentration using ridge regression, into a composite score, which can stratify the DPN patients into low, medium and high-risk groups. Our results here show activation of inflammatory pathway in DPN patients, and could be a potential clinical tool to identify T1D patients for therapeutic intervention of anti-inflammatory therapies.