This study focused on the relationship between food insecurity and medical mistrust within Appalachia. Food insecurity has negative consequences on health, while medical mistrust can lead to a ...decrease in health care use, creating additive consequences to already vulnerable populations. Medical mistrust has been defined in various ways, with measures addressing health care organizations and individual health care providers. To determine whether food insecurity has an additive impact on medical mistrust, a cross-sectional survey was completed by 248 residents in Appalachia Ohio while attending community or mobile clinics, food banks, or the county health department. More than one-quarter of the respondents had high levels of mistrust toward health care organizations. Those with high food insecurity levels were more likely to have higher levels of medical mistrust than those with lower levels of food insecurity. Individuals with higher self-identified health issues and older participants had higher medical mistrust scores. Screening for food insecurity in primary care can reduce the impact of mistrust on patient adherence and health care access by increasing patient-centered communication. These findings present a unique perspective on how to identify and mitigate medical mistrust within Appalachia and call attention to the need for further research on the root causes among food insecure residents.
Tirzepatide (TZP), a once-weekly GIP/GLP-1 receptor agonist, achieved significantly greater HbA1c and body weight (BW) reductions with all doses (5, 10, 15 mg) vs placebo (SURPASS-1 S-1) and ...semaglutide (SEMA) 1 mg (SURPASS-2 S-2) in randomized Phase 3 trials in people with type 2 diabetes controlled by diet and exercise (S-1) or metformin (S-2). Exploratory post hoc analyses examined changes from baseline in HbA1c and BW in these studies at 40 weeks across HOMA2-B (C-peptide) and HOMA2-IR (insulin) quartiles (Q) from low (lower beta-cell function/insulin resistance) (Q1) to high (Q4) as assessed by mixed model repeated measures (MMRM). HbA1c reductions were greater with all TZP doses than placebo or SEMA within each HOMA2-B and HOMA2-IR baseline Q. HbA1c reductions were largest in people within HOMA-2B Q1, yet similar across all HOMA2-IR Qs (Fig). BW reductions were greater across Qs with all TZP doses (ranging from 6%-14%) than placebo (up to 2%) or SEMA (up to 7%). TZP was more efficacious than placebo or SEMA in reducing HbA1c and BW across a spectrum of pancreatic beta-cell function, notably achieving greater glycemic improvement in people with markers of diminished pancreatic beta cell function at baseline.
Disclosure
J.M.Maldonado: Employee; Eli Lilly and Company. C.De block: Advisory Panel; Abbott Diagnostics, Indigo Diabetes, Insulet Corporation, Eli Lilly and Company, Novo Nordisk, Research Support; Boehringer-Ingelheim, AstraZeneca, Indigo Diabetes, Eli Lilly and Company, Speaker's Bureau; Novo Nordisk. J.P.Frias: Advisory Panel; Becton, Dickinson and Company, Pfizer Inc., Sanofi, Consultant; Akero Therapeutics, Inc., 89bio, Inc., Aimmune, Boehringer Ingelheim Inc., Eli Lilly and Company, Carmot Therapeutics, Inc., Echosens, Merck & Co., Inc., Metacrine, Inc., Novo Nordisk, Pfizer Inc., Sanofi, Employee; Ionis Pharmaceuticals, Research Support; Akero Therapeutics, Inc., 89bio, Inc., Altimmune, Axcella Health Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Carmot Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Metacrine, Inc., Novo Nordisk, Oramed Pharmaceuticals, Novartis, Pfizer Inc., Sanofi, Speaker's Bureau; Eli Lilly and Company, Sanofi. C.Lee: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. K.Brown: Employee; Eli Lilly and Company. H.Wang: None. M.K.Thomas: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company.
Funding
Eli Lilly and Company
Sperm competition theory predicts that males should allocate sperm according to the number of competing ejaculates. Prudent allocation of sperm in response to different levels of sperm competition ...has been found across a number of taxa; however, some studies suggest that males may not always allocate sperm as expected. Here we examine sperm allocation in the Australian field cricketTeleogryllus oceanicus, using female mating status (virgin, singly mated, or multiply mated) to manipulate male perception of sperm competition risk and intensity. Consistent with theory, we found that male crickets adjust their ejaculates in response to female mating status. However, rather than altering the absolute numbers of sperm transferred to a female, males altered the quality of their sperm. Males ejaculated sperm of low viability (proportion of live vs. dead sperm) when mating with virgins, increased sperm viability when mating with singly mated females, but reduced sperm viability when mating with multiply mated females. Our results show that variation in ejaculate quality can be an important aspect of strategic ejaculation by males and suggest caution in the interpretation of studies in which males do not appear to allocate sperm according to theory.
To assess the prevalence of therapy-related kidney outcomes in survivors of Wilms tumor (WT).
This prospective cohort study included survivors of WT who were ≥5 years old and ≥1 year from completing ...therapy, excluding those with preexisting hypertension, prior dialysis, or kidney transplant. Participants completed 24-hour ambulatory blood pressure monitoring (ABPM). Abnormal blood pressure (BP) was defined as ≥90th percentile. Masked hypertension was defined as having normal office BP and abnormal ABPM findings. Urine was analyzed for kidney injury molecule-1, interleukin-18, epidermal growth factor, albumin, and creatinine. The estimated glomerular filtration rate (eGFR) was calculated using the bedside chronic kidney disease in children equation. Recent kidney ultrasound examinations and echocardiograms were reviewed for contralateral kidney size and left ventricular hypertrophy, respectively. Clinical follow-up data were collected for approximately 2 years after study enrollment.
Thirty-two participants (median age, 13.6 years IQR, 10.5-16.3 years; 75% stage 3 or higher WT) were evaluated at a median of 8.7 years (IQR, 6.5-10.8 years) after therapy; 29 participants underwent unilateral radical nephrectomy, 2 bilateral partial nephrectomy, and 1 radical and contralateral partial nephrectomy. In this cohort, 72% received kidney radiotherapy and 75% received doxorubicin. Recent median eGFR was 95.6 mL/min/1.73 m2 (IQR, 84.6-114.0; 11 34% had an eGFR of <90 mL/min/1.73 m2). Abnormal ABPM results were found in 22 of 29 participants (76%), masked hypertension in 10 of 29 (34%), and microalbuminuria in 2 of 32 (6%). Of the 32 participants, 22 (69%) had abnormal epidermal growth factor; few had abnormal kidney injury molecule-1 or interleukin-18. Seven participants with previous unilateral nephrectomy lacked compensatory contralateral kidney hypertrophy. None had left ventricular hypertrophy.
In survivors of WT, adverse kidney outcomes were common and should be closely monitored.
Summary
To determine whether mitochondrial dysfunction is causally related to muscle atrophy with aging, we examined respiratory capacity, H2O2 emission, and function of the mitochondrial ...permeability transition pore (mPTP) in permeabilized myofibers prepared from four rat muscles that span a range of fiber type and degree of age‐related atrophy. Muscle atrophy with aging was greatest in fast‐twitch gastrocnemius (Gas) muscle (−38%), intermediate in both the fast‐twitch extensor digitorum longus (EDL) and slow‐twitch soleus (Sol) muscles (−21%), and non‐existent in adductor longus (AL) muscle (+47%). In contrast, indices of mitochondrial dysfunction did not correspond to this differential degree of atrophy. Specifically, despite higher protein expression for oxidative phosphorylation (oxphos) system in fast Gas and EDL, state III respiratory capacity per myofiber wet weight was unchanged with aging, whereas the slow Sol showed proportional decreases in oxphos protein, citrate synthase activity, and state III respiration. Free radical leak (H2O2 emission per O2 flux) under state III respiration was higher with aging in the fast Gas, whereas state II free radical leak was higher in the slow AL. Only the fast muscles had impaired mPTP function with aging, with lower mitochondrial calcium retention capacity in EDL and shorter time to mPTP opening in Gas and EDL. Collectively, our results underscore that the age‐related changes in muscle mitochondrial function depend largely upon fiber type and are unrelated to the severity of muscle atrophy, suggesting that intrinsic changes in mitochondrial function are unlikely to be causally involved in aging muscle atrophy.
Early detection of target non-indigenous species is one of the most important determinants of a successful eradication campaign. For early detection to be successful, and provide the highest ...probability of achieving eradication, intense surveillance is often required that can involve significant resources. Volunteer based monitoring or “citizen science” is one potential tool to address this problem. This study differs from standard citizen science projects because the participants are personnel or contractors of a company working on Barrow Island, Western Australia. We show that personnel can contribute successfully to a surveillance program aimed at detecting a broad taxonomic range of non-indigenous vertebrate and invertebrate species. Using data collected over a five year surveillance period on Barrow Island, we show that eighteen of the nineteen (95%) non-indigenous invertebrate species new to the island were detected by personnel working on the island, and that the number of detections made by these workers was significantly related to the number of personnel on the island at any one time. Most personnel detections (91%) were made inside buildings where the majority of active surveillance tools could not be implemented. For vertebrates, 4 NIS species detections (100% of detections) were made in the built environment by personnel. Although reporting of suspect non-indigenous species is voluntary, personnel are required to attend inductions and toolboxes where reporting of suspect biosecurity risk material is encouraged. These results demonstrate the value of industry led ‘citizen science’ programs, resulting in sustained stewardship and conservation of areas with high environmental value.
The rs7903146 T allele in transcription factor 7 like 2 (
) is strongly associated with type 2 diabetes (T2D), but the mechanisms for increased risk remain unclear. We evaluated the physiologic and ...hormonal effects of
genotype before and after interventions that influence glucose physiology.
We genotyped rs7903146 in 608 individuals without diabetes and recorded biochemical data before and after
) one dose of glipizide (5 mg) on visit 1 and
) a 75-g oral glucose tolerance test (OGTT) performed after administration of metformin 500 mg twice daily over 2 days. Incretin levels were measured in 150 of the 608 participants.
TT risk-allele homozygotes had 1.6 mg/dL higher baseline fasting glucose levels and 2.5 pg/mL lower glucagon levels per T allele than carriers of other genotypes at baseline. In a subset of participants, the T allele was associated with higher basal glucagon-like peptide 1 (GLP-1) levels at visit 1 (β = 1.52,
= 0.02 and β = 0.96,
= 0.002 for total and active GLP-1, respectively), and across all points of the OGTT after metformin administration. Regarding drug response, the T allele was associated with a shorter time (β = -7.00,
= 0.03) and a steeper slope (β = 0.23,
= 0.04) to trough glucose levels after glipizide administration, and lower visit 2 fasting glucose level adjusted for visit 1 fasting glucose level (β = -1.02,
= 0.04) and a greater decline in glucose level between visits (β = -1.61,
= 0.047) after metformin administration.
Our findings demonstrate that common variation at
influences acute responses to both glipizide and metformin in people without diabetes and highlight altered incretin signaling as a potential mechanism by which
variation increases T2D risk.
The endocrine hormone FGF21 has attracted considerable interest as a potential therapeutic for treating diabetes and obesity. As an alternative to the native cytokine, we generated bispecific Avimer ...polypeptides that bind with high affinity and specificity to one of the receptor and coreceptor pairs used by FGF21, FGFR1c and β-Klotho. These Avimers exhibit FGF21-like activity in in vitro assays with potency greater than FGF21. In a study conducted in obese male cynomolgus monkeys, animals treated with an FGFR1c/β-Klotho bispecific Avimer showed improved metabolic parameters and reduced body weight comparable to the effects seen with FGF21. These results not only demonstrate the essential roles of FGFR1c and β-Klotho in mediating the metabolic effects of FGF21, they also describe a first bispecific activator of this unique receptor complex and provide validation for a novel therapeutic approach to target this potentially important pathway for treating diabetes and obesity.
Global declines in insect abundance are of significant concern. While there is evidence that climate change is contributing to insect declines, we know little of the direct mechanisms responsible for ...these declines. Male fertility is compromised by increasing temperatures, and the thermal limit to fertility has been implicated as an important factor in the response of insects to climate change. However, climate change is affecting both temperature and hydric conditions, and the effects of water availability on male fertility have rarely been considered. Here we exposed male crickets Teleogryllus oceanicus to either low or high‐humidity environments while holding temperature constant. We measured water loss and the expression of both pre‐ and postmating reproductive traits. Males exposed to a low‐humidity environment lost more water than males exposed to a high‐humidity environment. A male's cuticular hydrocarbon profile (CHC) did not affect the amount of water lost, and males did not adjust the composition of their CHC profiles in response to hydric conditions. Males exposed to a low‐humidity environment were less likely to produce courtship song or produced songs of low quality. Their spermatophores failed to evacuate and their ejaculates contained sperm of reduced viability. The detrimental effects of low‐humidity on male reproductive traits will compromise male fertility and population persistence. We argue that limits to insect fertility based on temperature alone are likely to underestimate the true effects of climate change on insect persistence and that the explicit incorporation of water regulation into our modeling will yield more accurate predictions of the effects of climate change on insect declines.
The thermal limit to fertility has been implicated as a factor in the response of insects to climate change. However, climate change is also affecting hydric conditions. We demonstrate strong effects of hydration stress on mating behavior and male fertility that will adversely affect insect reproduction under climate change.
Background/Aim: Greater visceral fat area (VFA) is associated with multiple metabolic conditions. We sought to determine whether plasma amino acid concentrations (AA) predict VFA. Methods: In plasma ...samples from Japanese American participants in a study of diabetes risk factors, we used mass spectrometry to measure fasting levels of 20 AA in 351 individuals who were free from diabetes (mean age 56 y, 51% male). We measured height, weight, waist circumference (WC), and VFA and subcutaneous fat area (SFA). Using AA that were significantly associated with VFA in univariate analyses, we fitted a multivariable linear regression model to create a VFA prediction index. We calculated area under receiver-operating characteristic curves (AUROC) for ability of AA to discriminate between low vs. high VFA dichotomized at median values (men - 99.3 cm2, women - 65.6 cm2) and compared our AA estimates to WC AUROC. Results: All AA significantly discriminated between high and low VFA as all AUROC significantly exceeded the null value of 0.5 (Table 1). However, WC AUROC was significantly greater than all AA. Our new AA-based VFA prediction index performed better at distinguishing between high and low VFA than a previously reported index (Yamakado M et al., Clin Obesity, 2012, AUROC 0.780 vs. 0.676, p-value <0.005).
PDF
