A ten-year overview of cancer genetic family history screening in Georgia's Latina population.

Background: Population-based cancer genetic family history (FH) screening to identify families at high risk for BRCA-associated cancers has been endorsed by national public health policies. This report aimed to describe the utilization of FH screening services from 2013 to 2022 according to rurality and socioeconomic deprivation among Latinas in Georgia. Methods: Women who attended a medical appointment at participating Georgia Public Health Clinics were invited to complete FH screening. Screening results and participant zip code were reviewed. Area deprivation index (ADI) was measured at the census block group level and dichotomized (more deprived and less deprived). Rurality was measured through Rural-Urban Commuting Area (RUCA) codes and dichotomized (urban and rural). The ADI and RUCA codes were linked to participant data by zip code to characterize FH utilization among the Latina community. Results: Of the 9,330 adult Latinas in Georgia that completed cancer genetic FH screening, 9,066 (97.17%) women screened negative, and 264 (2.83%) screened positive (i.e., FH suggestive of higher risk for carrying BRCA1/2 mutations compared to the general population). Screening completion was higher among Latinas in urban areas (n = 7,871) compared to rural areas (n = 1,459). Screening completion was also higher in more socially deprived areas (n = 5,207) compared to less socially deprived areas (n = 4,123). Conclusion: Georgia's FH screening program reached Latinas across Georgia, particularly those living in urban, socially deprived areas. To ensure equitable cancer genetic screening dissemination, future efforts should prioritize tailored outreach in rural regions and comprehensive evaluations to identify key determinants of screening trends among Georgia's Latina population.

COVID-19 olfactory dysfunction: associations between coping, quality of life, and mental health.

BACKGROUND: Persistent olfactory dysfunction (OD) is a common symptom following SARS-CoV-2 infection that can greatly impact quality of life (QoL). Because coping strategies have been shown to moderate the effect of disease symptoms on functional and affective outcomes, this study aims to determine whether specific coping strategies are associated with and moderate QoL outcomes. METHODOLOGY: Participants with prior SARS-CoV-2 infection underwent psychophysical olfactory testing with Sniffin’ Sticks and completed questionnaires to elicit subjective olfactory function, coping strategies, olfactory-specific QoL, general QoL, and mental health. RESULTS: There were 93 participants included in the study. Olfactory specific QoL scores were significantly worse among individuals with subjective and psychophysically measured OD compared to those with subjective and psychophysically confirmed normosmia. Olfactory-specific QoL, general QoL, and anxiety symptom scores were positively correlated with avoidant and disengagement coping among individuals with subjective and psychophysically measured OD. Depression symptom scores were positively correlated with avoidant and disengagement coping and negatively correlated with approach and engagement coping. There were no significant moderating effects on the association between olfactory performance and QoL or mental health screening assessment. CONCLUSIONS: Approach and engagement coping mechanisms are associated with improved depression, whereas avoidant and disengagement coping tracks with worse QoL and mental health screening assessment, offering an opportunity to counsel patients accordingly.

Research needs, environmental concerns, and logistical considerations for incorporating livestock grazing into coastal upland habitat management.

Along the Gulf of Mexico (GoM) coast, natural resource managers continually struggle with managing coastal uplands due to front-end costs, prolonged maintenance, and habitat-specific ecological needs. Prescribed fire, mechanical removal, and chemical treatments are common habitat management techniques used to remove invasive species, clear understory, and achieve other management goals. However, rapid development and changing climate exacerbate the difficulty in using these techniques. A potential alternative or complementary technique is using livestock for habitat management (i.e., targeted or controlled grazing). In other regions of the world, using livestock for conservation or restoration of managed lands has shown to be a less intrusive and more financially viable alternative. To better understand the research needs, logistical, and environmental concerns related to using livestock for habitat management in the coastal uplands of the GoM, we developed and distributed a survey to three groups of land users, including natural resource managers, researchers, and livestock producers in the region. Survey results show that over 96% of respondents are interested in using livestock for habitat management, but less than 10% of respondents were aware of any information that could be used to inform grazing practices for coastal upland habitat management along the Gulf of Mexico coast. There were differences among surveyed groups, but generally small-sized cattle breeds and goats were identified as the livestock with the most potential for environmental benefit and ease of containment. General concerns and areas for further investigation were implementation (e.g., which livestock type to use and grazing intensity), logistical considerations (e.g., fencing and rotational frequency), impacts of grazing on water quality, wildlife, vegetation, and livestock nutrition. Survey respondents overwhelmingly (at least 75% of each group) indicated that livestock grazing ideally would not be a standalone management practice and should be used in conjunction with other habitat management techniques such as prescribed burns, mechanical clearing, or chemical treatments. The results of the survey could be used to develop applied research projects and guidance documents that directly address informational needs related to using livestock for habitat management of coastal uplands along the Gulf of Mexico coast.

The influence of environmental gradients on individual behaviour: Individual plasticity is consistent across risk and temperature gradients.

The expression of individual behaviour as a function of environmental variation (behavioural plasticity) is recognized as a means for animals to modify their phenotypes in response to changing conditions. Plasticity has been studied extensively in recent years, leading to an accumulation of evidence for behavioural plasticity within natural populations. Despite the recent attention given to studying individual variation in behavioural plasticity, there is still a lack of consensus regarding its causes and constraints. One pressing question related to this is whether individual plasticity carries over across temporal and environmental gradients. That is, are some individuals more plastic (responsive) than others in general? Here, we examined the influence of temporal and environmental gradients on individual behavioural responses in a marine gastropod, Littoraria irrorata. We measured individual boldness repeatedly over time and in response to tidal cycle (high vs. low, an index of risk) and daily temperature fluctuations (known to affect metabolism), in a controlled field experiment. On average, boldness increased from high to low tide and with increasing temperature but decreased marginally over time. Individuals also differed in their responses to variation in tide and temperature, but not over time. Those which were relatively bold at high tide (when predation risk is greater) were similarly bold at low tide, whereas shy individuals became much more "bold" at low tide. Most notably, individuals that were more responsive to tide (and thus risk) were also more responsive to temperature changes, indicating that plasticity was correlated across contexts (r = 0.57) and that bolder individuals were least plastic overall. This study provides a rare and possibly first example of consistency of individual behavioural plasticity across contexts, suggesting underlying physiology as a common mechanism, and raises the possibility of correlational selection on plasticity.

Characterization of Interfacial Structure in Polymer-Fullerene Bulk Heterojunctions via

We introduce a new application of solid state NMR measurements towards characterizing the donor-acceptor interfaces within bulk heterojunction (BHJ) films. Rotational echo double resonance (REDOR) is used to measure dipolar couplings between ^{13}C nuclei on the acceptor phenyl-C_{61}-butyric acid methyl ester (PCBM) fullerene cage, which is ≈18% isotopically enriched with ^{13}C, and beta hydrogens on the donor poly(3-hexyl thiophene) (P3HT) main chain, which are >95% isotopically enriched with ^{2}H. The ^{13}C-^{2}H dipolar couplings are used for constraining possible models of molecular packing in the amorphous mixed phase of a P3HT/PCBM BHJ. The films studied are highly mixed (>80%) and have a maximum length scale of composition nonuniformity of ≈6 nm in the mixed phase, as demonstrated by ^{1}H spin diffusion NMR and supported by TEM. The REDOR results show that despite the lack of phase separation at length scales greater than ≈6 nm, neat P3HT and PCBM clusters exist on ≈3 nm size scales, and, for the average PCBM molecule, the number of nearest neighbors P3HTs is two.

Prevalence of PALB2 mutations in the Creighton University Breast Cancer Family Registry.

The purpose of this study is to determine the prevalence of PALB2 mutations among breast cancer families from the United States. The PALB2 gene was screened for mutations in 90 familial breast cancer patients from the Creighton University Breast Cancer Family Registry. These patients had previously tested negative for mutations in BRCA1 and BRCA2. Two of 90 breast cancer patients (2.2 %) were found to carry a truncating mutation in PALB2 (c.2411_2412delCT and c.2053delC). Both probands were diagnosed with breast cancer before age 35 and each had three relatives with breast cancer. Mutations in PALB2 are less common than BRCA1 and BRCA2 in familial breast cancer patients. However, testing for PALB2 mutations is a useful adjunct for patients undergoing testing for BRCA1 and BRCA2.

Vaginal birth after cesarean success in high-risk women: a population-based study.

OBJECTIVE: The study aim was to identify factors associated with vaginal birth after cesarean (VBAC) in high-risk women. STUDY DESIGN: This is a population-based retrospective cohort study of all births in Ohio during 2006 and 2007. High-risk patients were defined as singleton gestations in women with one previous cesarean who had ⩾1 of the following risk factors: body mass index (BMI)⩾30, hypertension, or diabetes. Multivariate logistic regression was utilized to estimate the relative influence of each factor on successful VBAC. RESULT: A total of 280 882 births were analyzed: of them, 79 084 (27.1%) were high-risk pregnancies and 8658 (10.9%) women had undergone one previous cesarean; 1433 (16.6%) underwent a trial of labor after cesarean (TOLAC). Of them, 974 (68.0%) had a successful VBAC, whereas 459 (32.0%) did not. Factors significantly associated with VBAC success were as follows: a prior vaginal delivery; pregnancy weight gain ⩽30 lbs; Caucasian race; and labor augmentation. CONCLUSION: High-risk women with one prior cesarean are unlikely to undergo a TOLAC, but have a high rate of VBAC.

Retrospective evaluation of canine and feline maxillomandibular trauma cases. A comparison of signalment with non-maxillomandibular traumatic injuries (2003-2012).

OBJECTIVES: To determine differences in signalment between maxillomandibular (MM) and non-maxillomandibular (non-MM) trauma patients to help predict the type of injury sustained. METHODS: A medical records database was searched from December 2003 to September 2012 to identify all MM trauma patients. A random sample of non-MM trauma patients was generated for comparison. Patient species, age, sex, weight, and injury aetiology were recorded for both populations. RESULTS: Sixty-seven MM trauma patients and 129 non-MM trauma patients were identified. Feline patients were almost twice as likely to be presented for MM trauma compared with non-MM trauma. The median weight of canine patients suffering MM injury was significantly less than that of non-MM patients (p = 0.025). A significant association existed between the causes of injuries associated with MM and non-MM trauma populations (p = 0.000023). The MM trauma patients were more likely to sustain injury as a result of an animal altercation (Bonferroni p = 0.001) while non-MM injuries were more likely to result from motor vehicle accidents (Bonferroni p = 0.001). Overall, animals that were less than one year of age with traumatic injuries were overrepresented (65/196) in comparison to the entire patient population. CLINICAL SIGNIFICANCE: The results of this study may help guide clinicians in the evaluation and screening of trauma patients that are presented as an emergency. Cats, small dogs and animals suffering from animal altercations should all be closely evaluated for MM injury.

Retrospective evaluation of canine and feline maxillomandibular trauma cases. Comparison of lunar cycle and seasonality with non-maxillomandibular traumatic injuries (2003-2012).

OBJECTIVES: To determine relationships between seasonality and lunar cycle and the frequency of maxillomandibular (MM) and non-maxillomandibular (non-MM) injury in canine and feline trauma patients. METHODS: A medical records database was searched to identify all MM trauma patients (n = 67) and a random sample of non-MM trauma patients (n = 129) according to search criteria. Season of injury, moon phase, and moon luminosity were calculated for the date of injury. RESULTS: Maxillomandibular injury occurred predominately in the spring and decreased through winter while non-MM injury occurred more frequently in the summer and fall. The difference in the frequency of MM and non-MM injuries during different seasons was not significant (p = 0.071). When comparing the amount of moon illuminated when injuries occurred during the quarters before or after the full moon, a difference (p = 0.007) was noted with a greater number of injuries occurring immediately following the full moon. CLINICAL SIGNIFICANCE: These results may guide clinicians to closely evaluate trauma patients that are presented on emergency during a particular season or lunar phase. Based on the season at the time of injury, close evaluation for MM versus non-MM trauma may be appropriate.

Communication and technology in genetic counseling for familial cancer.

When a cancer predisposing germline mutation is detected in an index case, the presence of the underlying syndrome is confirmed and the potential for predictive testing of at-risk relatives is established. However, the reporting of a positive family history does not routinely lead to communication of information about risk to close, much less distant relatives. This review summarizes information technology utilized to address penetration or 'reach' of knowledge of risk within extended families, including the use of telephone and video counseling to reach distant patients, and anticipate novel internet-based processes for communication between investigators and relatives.

Hereditary ovarian and breast cancer: what have we learned?

An autosomal-dominant inherited trait predisposing women to both breast cancer (BC) and ovarian cancer (OC) was first described in 1971. Subsequent strides were made in identifying mutations in the eventually cloned genes BRCA1 and BRCA2 as being responsible for hereditary BC and OC (HBOC) in many women with early-onset HBOC. More recently, modifiers of BC risk have also been identified and are under study. The biological and molecular genetic pathways for malignant transformation in OC (ovarian epithelium and/or epithelium of the fallopian tube or, possibly, the endometrium and endocervix) remain elusive. The answer to the question 'What have we learned?' which is part of our chapter title unfortunately remains incomplete. However, intensive worldwide research indicates that its malignant transformation is the product of a multi-step process where there is an array of mutations which account for three or more classes of genes, inclusive of proto-oncogenes, tumor suppressor genes and mutator genes. This causal uncertainty heralds an enormous clinical-pathology dilemma, given the fact that epithelial OC, together with related Müllerian duct carcinoma, harbor the highest fatality rates of all gynecologic malignancies.

Prevalence and nature of dentoalveolar injuries among patients with maxillofacial fractures.

OBJECTIVE: Although not previously reported, experience suggests that dentoalveolar injury is -common among patients with maxillofacial fractures. The objective of this study was to evaluate and describe the prevalence and nature of dentoalveolar injuries in patients identified with maxillofacial fractures. METHODS: Medical records of 43 dogs and cats diagnosed with maxillofacial fractures between 2005 and 2012 were reviewed to identify patients with concurrent dentoalveolar injury. Medical records of patients with dentoalveolar injury were abstracted for the following information: signalment (including sex, age and skull type), mechanism of maxillofacial trauma, location and number of maxillofacial fractures, dentoalveolar injury type and location and the number of dentoalveolar injury per patient. Statistical evaluation was performed to determine associations between signalment, mechanism of trauma, location and number of maxillofacial fractures and the prevalence and nature of concurrent dentoalveolar injury. RESULTS: Dentoalveolar injuries are common among patients with maxillofacial trauma. Age and mechanism of trauma are significant predictors of the presence of dentoalveolar injuries in patients with maxillofacial trauma. CONCLUSIONS AND CLINICAL RELEVANCE: The findings of this study serve to encourage veterinarians to fully assess the oral cavity in patients with maxillofacial fractures as dentoalveolar injuries are common and can be predicted by age and mechanism of trauma.

Acute testosterone deprivation reduces insulin sensitivity in men.

OBJECTIVE: In men with prostate cancer, androgen deprivation reduces insulin sensitivity; however, the relative roles played by testosterone and estradiol are unknown. To investigate the respective effects of these hormones on insulin sensitivity in men, we employed a model of experimental hypogonadism with or without hormone replacement. DESIGN: Placebo-controlled, randomized trial. PARTICIPANTS: Twenty-two healthy male volunteers, 18-55 years old. METHODS: Following screening, subjects received the gonadotrophin-releasing hormone antagonist acyline plus one of the following for 28 days: Group 1, placebo transdermal gel and placebo pills; Group 2, transdermal testosterone gel 10 g/day plus placebo pills; Group 3, transdermal testosterone gel 10 g/day plus the aromatase inhibitor anastrozole 1 mg/day to normalize testosterone while selectively reducing serum estradiol. Fasting insulin, glucose, adipokines and hormones were measured bi-weekly. RESULTS: With acyline administration, serum testosterone was reduced by >90% in all subjects in Group 1. In these men, mean fasting insulin concentrations were significantly increased compared with baseline (P = 0·02) at 28 days, despite stable body weight and no changes in fasting glucose concentrations. Decreased insulin sensitivity was also apparent in the insulin sensitivity indices homeostasis model of insulin resistance (P = 0·03) and quantitative insulin sensitivity check index (P = 0·04). In contrast, in Groups 2 and 3, testosterone concentrations remained in the physiologic range, despite significant reduction in mean estradiol in Group 3. In these groups, no significant changes in insulin sensitivity were observed. CONCLUSIONS: Acute testosterone withdrawal reduces insulin sensitivity in men independent of changes in body weight, whereas estradiol withdrawal has no effect. Testosterone appears to maintain insulin sensitivity in normal men.

7 Tesla (T) human cardiovascular magnetic resonance imaging using FLASH and SSFP to assess cardiac function: validation against 1.5 T and 3 T.

We report the first comparison of cardiovascular magnetic resonance imaging (CMR) at 1.5 T, 3 T and 7 T field strengths using steady state free precession (SSFP) and fast low angle shot (FLASH) cine sequences. Cardiac volumes and mass measurements were assessed for feasibility, reproducibility and validity at each given field strength using FLASH and SSFP sequences. Ten healthy volunteers underwent retrospectively electrocardiogram (ECG) gated CMR at 1.5 T, 3 T and 7 T using FLASH and SSFP sequences. B1 and B0 shimming and frequency scouts were used to optimise image quality. Cardiac volume and mass measurements were not significantly affected by field strength when using the same imaging sequence (P > 0.05 for all parameters at 1.5 T, 3 T and 7 T). SSFP imaging returned larger end diastolic and end systolic volumes and smaller left ventricular masses than FLASH imaging at 7 T, and at the lower field strengths (P < 0.05 for each parameter). However, univariate general linear model analysis with fixed effects for sequence and field strengths found an interaction between imaging sequence and field strength (P = 0.03), with a smaller difference in volumes and mass measurements between SSFP and FLASH imaging at 7 T than 1.5 T and 3 T. SSFP and FLASH cine imaging at 7 T is technically feasible and provides valid assessment of cardiac volumes and mass compared with CMR imaging at 1.5 T and 3 T field strengths.

Comparison between eight- and sixteen-channel TEM transceive arrays for body imaging at 7 T.

Eight- and sixteen-channel transceive stripline/TEM body arrays were compared at 7 T (297 MHz) both in simulation and experiment. Despite previous demonstrations of similar arrays for use in body applications, a quantitative comparison of the two configurations has not been undertaken to date. Results were obtained on a male pelvis for assessing transmit, signal to noise ratio, and parallel imaging performance and to evaluate local power deposition versus transmit B(1) (B(1) (+) ). All measurements and simulations were conducted after performing local B(1) (+) phase shimming in the region of the prostate. Despite the additional challenges of decoupling immediately adjacent coils, the sixteen-channel array demonstrated improved or nearly equivalent performance to the eight-channel array based on the evaluation criteria. Experimentally, transmit performance and signal to noise ratio were 22% higher for the sixteen-channel array while significantly increased reduction factors were achievable in the left-right direction for parallel imaging. Finite difference time domain simulations demonstrated similar results with respect to transmit and parallel imaging performance, however, a higher transmit efficiency advantage of 33% was predicted. Simulations at both 3 and 7 T verified the expected parallel imaging improvements with increasing field strength and showed that, for a specific B(1) (+) shimming strategy used, the sixteen-channel array exhibited lower local and global specific absorption rate for a given B(1) (+) .

Management of anterior mediastinal masses in children.

BACKGROUND: Children with anterior mediastinal masses are at risk for life-threatening airway compromise during anesthesia, and can present a diagnostic and management challenge for pediatric surgeons. METHODS: We performed a retrospective chart review of all children presenting with an anterior mediastinal mass from 1994-2009. Parameters studied included demographics, historical and physical findings at diagnosis, radiographic evidence of airway compression, diagnostic studies, diagnosis, and complications. RESULTS: There were 26 patients with anterior mediastinal masses over a 15-year period. The mean age was 11.3 years, and there were no gender differences. The diagnoses were lymphoma (62%, 16/26), leukemia (15%, 4/26), and other (23%, 6/26). Diagnosis was made by CBC/peripheral smear in 2/4 patients with leukemia, by bone marrow biopsy in 2/4 patients with leukemia, by thoracentesis in 3/16 patients with lymphoma, by lymph node biopsies in 6/16 patients with lymphoma, and by biopsy of a mediastinal mass in 7/16 patients with lymphoma and in 6/6 patients with other diagnoses. Radiographic evidence of airway compression was seen in 62% (16/26) of children. Only 12% (3/26) had a tracheal cross-sectional area (TCA) <50%. Correlation of symptoms with anatomical airway obstruction or complications was poor. Pulmonary function studies were obtained in 38%, 10/26 children. Only 2 children had a PEFR (peak expiratory flow rate) <50% predicted. This data also correlated poorly with anatomical airway obstruction or complications. 3 patients had anesthesia-related complications: one desaturation during induction prior to median sternotomy, one with significant desaturation and bradycardia during biopsy under local anesthesia with minimal sedation, and one with prolonged (5 days) mechanical ventilation after general anesthesia. 2 of these patients had a TCA <50%, and 2 had SVC obstructions. There were no anesthesia-related deaths, and the overall survival was 85% (22/26). CONCLUSION: Anterior mediastinal masses in children should be approached in a step-wise fashion with multi-disciplinary involvement, starting with the least invasive techniques and progressing cautiously. The surgeon should have a well-defined and preoperatively established contingency plan if these children require general anesthesia for diagnosis.

Longitudinal modeling of frontal cognition in APOE ε4 homozygotes, heterozygotes, and noncarriers.

BACKGROUND: Fibrillar amyloid deposition preferentially affects the frontal lobes, temporal pole/neocortex, and posterior cingulate by age 65 years in APOE ε4 carriers prior to the diagnosis of mild cognitive impairment (MCI) and Alzheimer disease (AD), but is it impairing frontally mediated neuropsychological performance? METHODS: A total of 71 ε4 homozygotes (HMZ), 194 ε4 heterozygotes (HTZ), and 356 ε4 noncarriers (NC) who did not differ significantly in mean age (56.6 years), years of education (15.6), gender (70% women), or follow-up duration (6.3 years) had neuropsychological testing every 2 years including the Auditory Verbal Learning Test (AVLT) and frontal/executive tasks sensitive to psychomotor speed, working memory, problem solving, and activity. A subset also received the Iowa Gambling Task (IGT). Findings were then tested in a clinical sample of 27 patients with incident MCI and AD. RESULTS: APOE ε4 carriers had greater acceleration of decline (quadratic effect) than NC on the AVLT (p = 0.04) but not on any frontal test. APOE ε4 HMZ had greater velocity of decline (linear effects) than NC on all mental arithmetic tests: paced auditory serial attention task (PASAT) 3 second (p = 0.01) and 2 second (p = 0.004) versions; and Wechsler Adult Intelligence Scale-Revised arithmetic (p = 0.048). IGT performance did not differ between 12 ε4 HMZ, 27 ε4 HTZ, and 44 NC. Among 27 patients with incident MCI and AD, the PASAT showed progressive decline preceding diagnosis in 50%. CONCLUSIONS: No frontal cognitive effects were as robust as memory decline. APOE ε4 HMZ declined more quickly than NC on mental arithmetic tests related to frontal lobe-mediated working memory ability.

Cerebrovascular risk factors and preclinical memory decline in healthy APOE ε4 homozygotes.

OBJECTIVE: To characterize the effects of cerebrovascular (CV) risk factors on preclinical memory decline in cognitively normal individuals at 3 levels of genetic risk for Alzheimer disease (AD) based on APOE genotype. METHODS: We performed longitudinal neuropsychological testing on an APOE ε4 enriched cohort, ages 21-97. The long-term memory (LTM) score of the Auditory Verbal Learning Test (AVLT) was the primary outcome measure. Any of 4 CV risk factors (CVany), including hypercholesterolemia (CHOL), prior cigarette use (CIG), diabetes mellitus (DM), and hypertension (HTN), was treated as a dichotomized variable. We estimated the longitudinal effect of age using statistical models that simultaneously modeled the cross-sectional and longitudinal effects of age on AVLT LTM by APOE genotype, CVany, and the interaction between the two. RESULTS: A total of 74 APOE ε4 homozygotes (HMZ), 239 ε4 heterozygotes (HTZ), and 494 ε4 noncarriers were included. APOE ε4 carrier status showed a significant quadratic effect with age-related LTM decline in all models as previously reported. CVany was associated with further longitudinal AVLT LTM decline in APOE ε4 carriers (p=0.02), but had no effect in noncarriers. When ε4 HTZ and HMZ were considered separately, there was a striking effect in HMZ (p<0.001) but not in HTZ. In exploratory analyses, significant deleterious effects were found for CIG (p=0.001), DM (p=0.03), and HTN (p=0.05) in APOE ε4 carriers only that remained significant only for CIG after correction for multiple comparisons. CONCLUSION: CV risk factors influence age-related memory decline in APOE ε4 HMZ.