Development of the Children's English and Spanish Speech Recognition Test: Psychometric Properties, Feasibility, Reliability, and Normative Data.

OBJECTIVES: The Children's English and Spanish Speech Recognition (ChEgSS) test is a computer-based tool for assessing closed-set word recognition in English and in Spanish, with a masker that is either speech-shaped noise or competing speech. The present study was conducted to (1) characterize the psychometric properties of the ChEgSS test, (2) evaluate feasibility and reliability for a large cohort of Spanish/English bilingual children with normal hearing, and (3) establish normative data. DESIGN: Three experiments were conducted to evaluate speech perception in children (4-17 years) and adults (19-40 years) with normal hearing using the ChEgSS test. In Experiment 1, data were collected from Spanish/English bilingual and English monolingual adults at multiple, fixed signal-to-noise ratios. Psychometric functions were fitted to the word-level data to characterize variability across target words in each language and in each masker condition. In Experiment 2, Spanish/English bilingual adults were tested using an adaptive tracking procedure to evaluate the influence of different target-word normalization approaches on the reliability of estimates of masked-speech recognition thresholds corresponding to 70.7% correct word recognition and to determine the optimal number of reversals needed to obtain reliable estimates. In Experiment 3, Spanish/English bilingual and English monolingual children completed speech perception testing using the ChEgSS test to (1) characterize feasibility across age and language group, (2) evaluate test-retest reliability, and (3) establish normative data. RESULTS: Experiments 1 and 2 yielded data that are essential for stimulus normalization, optimizing threshold estimation procedures, and interpreting threshold data across test language and masker type. Findings obtained from Spanish/English bilingual and English monolingual children with normal hearing in Experiment 3 support feasibility and demonstrate reliability for use with children as young as 4 years of age. Equivalent results for testing in English and Spanish were observed for Spanish/English bilingual children, contingent on adequate proficiency in the target language. Regression-based threshold norms were established for Spanish/English bilingual and English monolingual children between 4 and 17 years of age. CONCLUSIONS: The present findings indicate the ChEgSS test is appropriate for testing a wide age range of children with normal hearing in either Spanish, English, or both languages. The ChEgSS test is currently being evaluated in a large cohort of patients with hearing loss at pediatric audiology clinics across the United States. Results will be compared with normative data established in the present study and with established clinical measures used to evaluate English- and Spanish-speaking children. Questionnaire data from parents and clinician feedback will be used to further improve test procedures.

Effects of Stimulus Type on 16-kHz Detection Thresholds.

OBJECTIVES: Audiometric testing typically does not include frequencies above 8 kHz. However, recent research suggests that extended high-frequency (EHF) sensitivity could affect hearing in natural communication environments. Clinical assessment of hearing often employs pure tones and frequency-modulated (FM) tones interchangeably regardless of frequency. The present study was designed to evaluate how the stimulus chosen to measure EHF thresholds affects estimates of hearing sensitivity. DESIGN: The first experiment used standard audiometric procedures to measure 8- and 16-kHz thresholds for 5- to 28-year olds with normal hearing in the standard audiometric range (250 to 8000 Hz). Stimuli were steady tones, pulsed tones, and FM tones. The second experiment tested 18- to 28-year olds with normal hearing in the standard audiometric range using psychophysical procedures to evaluate how changes in sensitivity as a function of frequency affect detection of stimuli that differ with respect to bandwidth, including bands of noise. Thresholds were measured using steady tones, pulsed tones, FM tones, narrow bands of noise, and one-third-octave bands of noise at a range of center frequencies in one ear. RESULTS: In experiment 1, thresholds improved with increasing age at 8 kHz and worsened with increasing age at 16 kHz. Thresholds for individual participants were relatively similar for steady, pulsed, and FM tones at 8 kHz. At 16 kHz, mean thresholds were approximately 5 dB lower for FM tones than for steady or pulsed tones. This stimulus effect did not differ as a function of age. Experiment 2 replicated this greater stimulus effect at 16 kHz than at 8 kHz and showed that the slope of the audibility curve accounted for these effects. CONCLUSIONS: Contrary to prior expectations, there was no evidence that the choice of stimulus type affected school-age children more than adults. For individual participants, audiometric thresholds at 16 kHz were as much as 20 dB lower for FM tones than for steady tones. Threshold differences across stimuli at 16 kHz were predicted by differences in audibility across frequency, which can vary markedly between listeners. These results highlight the importance of considering spectral width of the stimulus used to evaluate EHF thresholds.

Implementation and evaluation of a community-based mindful walking randomized controlled trial to sustain cognitive health in older African Americans at risk for dementia.

BACKGROUND: With an increasing proportion of older adults and the associated risk of Alzheimer's Disease and Related Dementias (ADRD) around the globe, there is an urgent need to engage in ADRD risk reduction efforts. African American (AA) older adults in the U.S. are disproportionally impacted by ADRD compared to other races and ethnicities. Mindful walking integrates two potentially protective factors of ADRD by elevating mindfulness and physical activity (i.e., walking), resulting in a synergistic behavioral strategy that is feasible and safe for older adults. However, the efficacy of applying this intervention for cognitive health outcomes has not been evaluated using experimental designs. METHODS: This paper documents the goal and protocol of a community-based, mindful walking randomized controlled trial to examine the short- and longer-term efficacy on cognitive and other health-related outcomes in ADRD at-risk AA older adults. The study outcomes include various brain health determinants, including cognitive function, quality of life, psychological well-being, physical activity, mindfulness, sleep, and overall health status. In addition, the estimated costs of program implementation are also collected throughout the study period. This study will recruit 114 older adults (ages 60+ years) with elevated ADRD risk from the Midlands region of South Carolina. Older adults are randomly assigned to participate in 24 sessions of outdoor mindful walking over three months or a delayed mindful walking group (n=57 in each group). Participants in both groups follow identical measurement protocols at baseline, after 12 weeks, after 18 weeks, and after 24 weeks from baseline. The outcome measures are administered in the lab and in everyday settings. Costs per participant are calculated using micro-costing methods. The eliciting participant costs for mindful walking engagement with expected results are reported using the payer and the societal perspectives. DISCUSSION: This study will generate evidence regarding the efficacy of mindful walking on sustaining cognitive health in vulnerable older adults. The results can inform future large-scale effectiveness trials to support our study findings. If successful, this mindful walking program can be scaled up as a low-cost and viable lifestyle strategy to promote healthy cognitive aging in diverse older adult populations, including those at greatest risk. TRIAL REGISTRATION: ClinicalTrials.gov number NCT06085196 (retrospectively registered on 10/08/2023).

A pathway for error-free non-homologous end joining of resected meiotic double-strand breaks.

Programmed DNA double-strand breaks (DSBs) made during meiosis are repaired by recombination with the homologous chromosome to generate, at selected sites, reciprocal crossovers that are critical for the proper separation of homologs in the first meiotic division. Backup repair processes can compensate when the normal meiotic recombination processes are non-functional. We describe a novel backup repair mechanism that occurs when the homologous chromosome is not available in Drosophila melanogaster meiosis. In the presence of a previously described mutation (Mcm5A7) that disrupts chromosome pairing, DSB repair is initiated by homologous recombination but is completed by non-homologous end joining (NHEJ). Remarkably, this process yields precise repair products. Our results provide support for a recombination intermediate recently proposed in mouse meiosis, in which an oligonucleotide bound to the Spo11 protein that catalyzes DSB formation remains bound after resection. We propose that this oligonucleotide functions as a primer for fill-in synthesis to allow scarless repair by NHEJ. We argue that this is a conserved repair mechanism that is likely to be invoked to overcome occasional challenges in normal meiosis.

Sociodemographic Characteristics of HIV-Associated Dementia in the South Carolina Alzheimer's Disease Registry.

OBJECTIVES: Studies examining the sociodemographic characteristics associated with human immunodeficiency virus (HIV)-associated dementia (HAD) are lacking, especially in the southern United States. The aim of this study was to describe the characteristics of HAD using South Carolina Alzheimer's Disease Registry data, and examine these characteristics across two time periods. METHODS: Data were obtained from the population-based, South Carolina Alzheimer's Disease Registry from 2000-2006 and 2010-2016 (N = 165,487). Crude and multivariable logistic regression models were applied to determine sociodemographic characteristics associated with HAD by time period. RESULTS: Younger, Black, Other, men, and urban populations had greater odds of being diagnosed as having HAD in both time periods. For example, compared with individuals aged 85 years and older, individuals aged 18 to 34 had 97 times the odds (adjusted odds ratio 97.0; 95% confidence interval 31.6-297.8) of being diagnosed as having HAD. In 2010-2016, however, nursing facility populations had a greater odds of being diagnosed as having HAD. CONCLUSIONS: We found that younger populations (younger than 74 years), communities of color, men, urban populations, and nursing facility populations were more likely to have HAD. Future research should focus on the association between HAD and risk for Alzheimer's disease.

Traditional Kenyan herbal medicine: exploring natural products' therapeutics against schistosomiasis.

Praziquantel (PZQ) remains the only drug of choice for the treatment of schistosomiasis, caused by parasitic flatworms. The widespread use of PZQ in schistosomiasis endemic areas for about four decades raises concerns about the emergence of resistance of Schistosoma spp. to PZQ under drug selection pressure. This reinforces the urgency in finding alternative therapeutic options that could replace or complement PZQ. We explored the potential of medicinal plants commonly used by indigenes in Kenya for the treatment of various ailments including malaria, pneumonia, and diarrhoea for their antischistosomal properties. Employing the Soxhlet extraction method with different solvents, seven medicinal plants Artemisia annua, Ajuga remota, Bredilia micranta, Cordia africana, Physalis peruviana, Prunus africana and Senna didymobotrya were extracted. Qualitative phytochemical screening was performed to determine the presence of various phytochemicals in the plant extracts. Extracts were tested against Schistosoma mansoni newly transformed schistosomula (NTS) and adult worms and the schistosomicidal activity was determined by using the adenosine triphosphate quantitation assay. Phytochemical analysis of the extracts showed different classes of compounds such as alkaloids, tannins, terpenes, etc., in plant extracts active against S. mansoni worms. Seven extracts out of 22 resulted in <20% viability against NTS in 24 h at 100 µg/ml. Five of the extracts with inhibitory activity against NTS showed >69.7% and ≥72.4% reduction in viability against adult worms after exposure for 24 and 48 h, respectively. This study provides encouraging preliminary evidence that extracts of Kenyan medicinal plants deserve further study as potential alternative therapeutics that may form the basis for the development of the new treatments for schistosomiasis.

Cognitive outcomes following frontal lobe resection for treatment of epilepsy in children and adolescents.

OBJECTIVE: To use reliable change indices (RCIs) developed specifically for pediatric patients with epilepsy to examine cognitive outcomes after frontal lobe resection for pharmacoresistant epilepsy. METHODS: Forty-one pediatric patients (25 male, Mage = 10 years) completed comprehensive neuropsychological evaluations before and an average of 6.5 months after frontal lobe resections for treatment of epilepsy. Evaluations included tests of intelligence, attention/working memory, processing speed, language, visuospatial skills, executive function, and episodic memory. Practice effect-adjusted RCIs were used to determine clinically significant postoperative cognitive change. Demographic, disease, and surgical variables were examined to identify factors associated with postoperative cognitive decline or improvement. RESULTS: Within each cognitive domain, there was a large proportion of patients (51-84%) who did not exhibit significant cognitive change. In terms of overall cognitive profile, 44% demonstrated improvement in at least one domain and 69% declined in at least one domain. Postoperative cognitive improvement occurred most commonly in the domain of processing speed, whereas postoperative cognitive decline occurred most frequently in the domain of visuospatial skills. Younger age at surgery was associated with cognitive improvement. Older age at seizure onset and higher baseline cognitive performance were associated with cognitive decline. SIGNIFICANCE: Approximately 6.5 months after frontal lobe resection, only 15% of our sample showed stable performance across all cognitive domains. Seventeen percent of patients showed improvements without declines, 42% showed declines without improvements, and 27% showed a mix of improvements and declines across different cognitive domains. Age and baseline abilities were associated with postoperative cognitive change on multiple measures. With 1 in 8 children demonstrating postoperative decline across three or more domains, further research is needed to identify factors associated with cognitive decline in order to inform clinical decision-making and patient/family counseling.

Feline Pituitary Adenomas: Correlation of Histologic and Immunohistochemical Characteristics With Clinical Findings and Case Outcome.

Pituitary glands from 141 feline autopsy cases were reviewed histologically. Adenoma and hyperplasia were the most common lesions at 13 cases each. Pituitary adenoma was more likely than hyperplasia to be associated with clinical evidence of endocrinopathy or an intracranial mass (P < .001). A histochemical and immunohistochemical panel was applied to 44 autopsy- or hypophysectomy-derived pituitary adenomas in 43 cats from 2 diagnostic laboratories. Adenomas were differentiated from hyperplasia by the presence of disrupted reticulin fibers. One cat had a double (somatotroph and melanotroph) adenoma. Twenty somatotroph adenomas consisted of periodic acid-Schiff (PAS)-negative acidophils that expressed growth hormone; 16/20 had hypersomatotropism; 17/20 had diabetes mellitus. Eleven melanotroph adenomas consisted of PAS-positive basophils or chromophobes that expressed melanocyte-stimulating and adrenocorticotrophic hormones; 5/11 had hypercortisolism; 6/11 had diabetes mellitus. Eleven gonadotroph adenomas consisted of PAS-negative chromophobes that expressed follicle-stimulating and/or luteinizing hormones. Two thyrotroph adenomas consisted of PAS-negative basophils or chromophobes that expressed thyroid-stimulating hormone. Pituitary-dependent disease was not recognized in cats with gonadotroph or thyrotroph adenomas. The Ki-67 proliferation index in hypophysectomy specimens was lower in somatotroph than in melanotroph adenomas. Fourteen cats with hypophysectomy-treated somatotroph or melanotroph adenoma had an 899-day median survival time versus 173 days in 17 nonsurgical cases. After adjusting for age, adenoma size and type, hypophysectomized cats had an overall better survival time than nonsurgical cases (P = .029). The study results underscore the value of hypophysectomy and trophic hormone immunohistochemistry in the treatment and classification of feline pituitary adenomas.

International Guidelines for Veterinary Tumor Pathology: A Call to Action.

Standardization of tumor assessment lays the foundation for validation of grading systems, permits reproducibility of oncologic studies among investigators, and increases confidence in the significance of study results. Currently, there is minimal methodological standardization for assessing tumors in veterinary medicine, with few attempts to validate published protocols and grading schemes. The current article attempts to address these shortcomings by providing standard guidelines for tumor assessment parameters and protocols for evaluating specific tumor types. More detailed information is available in the Supplemental Files, the intention of which is 2-fold: publication as part of this commentary, but more importantly, these will be available as "living documents" on a website (www.vetcancerprotocols.org), which will be updated as new information is presented in the peer-reviewed literature. Our hope is that veterinary pathologists will agree that this initiative is needed, and will contribute to and utilize this information for routine diagnostic work and oncologic studies. Journal editors and reviewers can utilize checklists to ensure publications include sufficient detail and standardized methods of tumor assessment. To maintain the relevance of the guidelines and protocols, it is critical that the information is periodically updated and revised as new studies are published and validated with the intent of providing a repository of this information. Our hope is that this initiative (a continuation of efforts published in this journal in 2011) will facilitate collaboration and reproducibility between pathologists and institutions, increase case numbers, and strengthen clinical research findings, thus ensuring continued progress in veterinary oncologic pathology and improving patient care.

Brief Cognitive Tests for Distinguishing Clinical Alzheimer-Type Dementia From Mild Cognitive Impairment or Normal Cognition in Older Adults With Suspected Cognitive Impairment.

BACKGROUND: The accuracy and harms of brief cognitive tests for identifying clinical Alzheimer-type dementia (CATD) are uncertain. PURPOSE: To summarize evidence on accuracy and harms of brief cognitive tests for CATD in older adults with suspected cognitive impairment. DATA SOURCES: Electronic bibliographic databases (from inception to November 2019) and systematic review bibliographies. STUDY SELECTION: English-language, controlled observational studies in older adults that evaluated the accuracy of brief cognitive tests (standalone tests; memory, executive function, and language tests; and brief multidomain batteries) for distinguishing CATD from mild cognitive impairment (MCI) or normal cognition as defined by established diagnostic criteria. Studies with low or medium risk of bias (ROB) were analyzed. DATA EXTRACTION: Two reviewers rated ROB. One reviewer extracted data; the other verified extraction accuracy. DATA SYNTHESIS: Fifty-seven studies met analysis criteria. Many brief, single cognitive tests were highly sensitive and specific for distinguishing CATD from normal cognition. These included standalone tests (clock-drawing test, median sensitivity 0.79 and specificity 0.88 [8 studies]; Mini-Mental State Examination, 0.88 and 0.94 [7 studies]; Montreal Cognitive Assessment, 0.94 and 0.94 [2 studies]; and Brief Alzheimer Screen, 0.92 and 0.97 [1 study]), memory tests (list delayed recall, 0.89 and 0.94 [5 studies]), and language tests (category fluency, 0.92 and 0.89 [9 studies]). Accuracy was lower in distinguishing mild CATD from normal cognition and distinguishing CATD from MCI. No studies reported on testing harms. LIMITATIONS: Studies were small. Few test metrics were evaluated by multiple studies. Few studies directly compared different tests, scores, cut points, or test combinations. CONCLUSION: Many brief, single cognitive tests accurately distinguish CATD from normal cognition in older adults but are less accurate in distinguishing mild CATD from normal cognition or CATD from MCI. No studies reported on testing harms. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018117897).

Benefits and Harms of Prescription Drugs and Supplements for Treatment of Clinical Alzheimer-Type Dementia.

BACKGROUND: Effects of drug treatment of clinical Alzheimer-type dementia (CATD) are uncertain. PURPOSE: To summarize evidence on the effects of prescription drugs and supplements for CATD treatment. DATA SOURCES: Electronic bibliographic databases (inception to November 2019), ClinicalTrials.gov (to November 2019), and systematic review bibliographies. STUDY SELECTION: English-language trials of prescription drug and supplement treatment in older adults with CATD that report cognition, function, global measures, behavioral and psychological symptoms of dementia (BPSD), or harms. Minimum treatment was 24 weeks (≥2 weeks for selected BPSD). DATA EXTRACTION: Studies with low or medium risk of bias (ROB) were analyzed. Two reviewers rated ROB. One reviewer extracted data; another verified extraction accuracy. DATA SYNTHESIS: Fifty-five studies reporting non-BPSD outcomes (most ≤26 weeks) and 12 reporting BPSD (most ≤12 weeks) were analyzed. Across CATD severity, mostly low-strength evidence suggested that, compared with placebo, cholinesterase inhibitors produced small average improvements in cognition (median standardized mean difference [SMD], 0.30 [range, 0.24 to 0.52]), no difference to small improvement in function (median SMD, 0.19 [range, -0.10 to 0.22]), no difference in the likelihood of at least moderate improvement in global clinical impression (median absolute risk difference, 4% [range, 2% to 4%]), and increased withdrawals due to adverse events. In adults with moderate to severe CATD receiving cholinesterase inhibitors, low- to insufficient-strength evidence suggested that, compared with placebo, add-on memantine inconsistently improved cognition and improved global clinical impression but not function. Evidence was mostly insufficient about prescription drugs for BPSD and about supplements for all outcomes. LIMITATION: Most drugs had few trials without high ROB, especially for supplements, active drug comparisons, BPSD, and longer trials. CONCLUSION: Cholinesterase inhibitors and memantine slightly reduced short-term cognitive decline, and cholinesterase inhibitors slightly reduced reported functional decline, but differences versus placebo were of uncertain clinical importance. Evidence was mostly insufficient on drug treatment of BPSD and on supplements for all outcomes. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018117897).

Caribbean reefs of the Anthropocene: Variance in ecosystem metrics indicates bright spots on coral depauperate reefs.

Dramatic coral loss has significantly altered many Caribbean reefs, with potentially important consequences for the ecological functions and ecosystem services provided by reef systems. Many studies examine coral loss and its causes-and often presume a universal decline of ecosystem services with coral loss-rather than evaluating the range of possible outcomes for a diversity of ecosystem functions and services at reefs varying in coral cover. We evaluate 10 key ecosystem metrics, relating to a variety of different reef ecosystem functions and services, on 328 Caribbean reefs varying in coral cover. We focus on the range and variability of these metrics rather than on mean responses. In contrast to a prevailing paradigm, we document high variability for a variety of metrics, and for many the range of outcomes is not related to coral cover. We find numerous "bright spots," where herbivorous fish biomass, density of large fishes, fishery value, and/or fish species richness are high, despite low coral cover. Although it remains critical to protect and restore corals, understanding variability in ecosystem metrics among low-coral reefs can facilitate the maintenance of reefs with sustained functions and services as we work to restore degraded systems. This framework can be applied to other ecosystems in the Anthropocene to better understand variance in ecosystem service outcomes and identify where and why bright spots exist.

Diagnosis of Collagen Type III Glomerulopathy Using Picrosirius Red and PASH/Masson's Trichrome Stain.

Canine collagen type III glomerulopathy (Col3GP) is a rare juvenile nephropathy in which irregular type III collagen fibrils and fibronectin accumulate in glomerular capillary walls and the mesangium. Necropsy findings were reviewed from 5 puppies diagnosed with Col3GP at 6 to 18 weeks of age. Histologically, with hematoxylin and eosin stain, the glomerular capillary walls and mesangium were diffusely and globally expanded by homogeneous pale eosinophilic material. Ultrastructurally, the subendothelial zone and mesangium were expanded by fibronectin and cross-banded collagen type III fibrils, diagnostic of Col3GP. Two additional stains were employed to identify the material within glomeruli as fibrillar collagen using light microscopy. In all 5 cases, the material was red with picrosirius red and birefringent under polarized light, and was blue with periodic acid-Schiff/hematoxylin/trichrome (PASH/TRI), thereby identifying it as fibrillar collagen. Based on these unique staining characteristics with picrosirius red and PASH/TRI, Col3GP may be reliably diagnosed with light microscopy alone.

Radiographic and computed tomographic appearance of caseous lymphadenitis in a goat.

A 2-year-old Boer doe was presented with respiratory distress and severe inspiratory dyspnea. Cervical and thoracic radiographs revealed a marked retropharyngeal soft tissue mass effect, several mineralized pharyngeal and retropharyngeal structures, and a pulmonary mass. Computed tomography (CT) revealed a severely enlarged right medial retropharyngeal lymph node, which caused laryngeal compression, leading to upper airway obstruction. Multiple cervical and thoracic lymph nodes, and the pulmonary mass had an irregular layered/laminated pattern of mineralization. Imaging findings were consistent with caseous lymphadenitis, and further confirmed with culture, necropsy, and histopathology. This is the first report of CT appearance of caseous lymphadenitis in a goat.

Inter-Institutional Partnerships to Develop Veterinarian-Investigators through the NIH Comparative Biomedical Scientist Training Program Benefit One Health Goals.

Limitations in workforce size and access to resources remain perennial challenges to greater progress in academic veterinary medicine and engagement between human and veterinary medicine (One Health). Ongoing resource constraints occur in part due to limited public understanding of the role veterinarians play in improving human health. One Health interactions, particularly through interdisciplinary collaborations in biomedical research, present constructive opportunities to inform resource policies and advance health care. To this end, inter-institutional partnerships between individual veterinary medical education programs (VMEPs) and several National Institutes of Health (NIH) intramural research programs have created synergies beyond those provided by individual programs. In the NIH Comparative Biomedical Scientist Training Program (CBSTP), interdisciplinary cross-training of veterinarians consisting of specialty veterinary medicine coupled with training in human disease research leading to a PhD, occurs collaboratively on both VMEP and NIH campuses. Pre-doctoral veterinary student research opportunities have also been made available. Through the CBSTP, NIH investigators and national biomedical science policy makers gain access to veterinary perspective and expertise, while veterinarians obtain additional opportunities for NIH-funded research training. CBSTP Fellows serve as de facto ambassadors enhancing visibility for the profession while in residence at NIH, and subsequently through a variety of university, industry, and government research appointments, as graduates. Thus, the CBSTP represents an inter-institutional opportunity that not only addresses critical needs for veterinarian-scientists in the biomedical workforce, but also simultaneously exposes national policy makers to veterinarian-scientists' specialized training, leading to more effective realization of One Health goals to benefit human and animal health.

Considerations for maximizing the adaptive potential of restored coral populations in the western Atlantic.

Active coral restoration typically involves two interventions: crossing gametes to facilitate sexual larval propagation; and fragmenting, growing, and outplanting adult colonies to enhance asexual propagation. From an evolutionary perspective, the goal of these efforts is to establish self-sustaining, sexually reproducing coral populations that have sufficient genetic and phenotypic variation to adapt to changing environments. Here, we provide concrete guidelines to help restoration practitioners meet this goal for most Caribbean species of interest. To enable the persistence of coral populations exposed to severe selection pressure from many stressors, a mixed provenance strategy is suggested: genetically unique colonies (genets) should be sourced both locally as well as from more distant, environmentally distinct sites. Sourcing three to four genets per reef along environmental gradients should be sufficient to capture a majority of intraspecies genetic diversity. It is best for practitioners to propagate genets with one or more phenotypic traits that are predicted to be valuable in the future, such as low partial mortality, high wound healing rate, high skeletal growth rate, bleaching resilience, infectious disease resilience, and high sexual reproductive output. Some effort should also be reserved for underperforming genets because colonies that grow poorly in nurseries sometimes thrive once returned to the reef and may harbor genetic variants with as yet unrecognized value. Outplants should be clustered in groups of four to six genets to enable successful fertilization upon maturation. Current evidence indicates that translocating genets among distant reefs is unlikely to be problematic from a population genetic perspective but will likely provide substantial adaptive benefits. Similarly, inbreeding depression is not a concern given that current practices only raise first-generation offspring. Thus, proceeding with the proposed management strategies even in the absence of a detailed population genetic analysis of the focal species at sites targeted for restoration is the best course of action. These basic guidelines should help maximize the adaptive potential of reef-building corals facing a rapidly changing environment.

Naming decline after epilepsy surgery is associated with subjective language complaints.

OBJECTIVE: This retrospective, observational study investigated the relationship between objective naming decline and patient report of subjective decline in language functioning following epilepsy surgery. The role of depression in this relationship was also examined. METHODS: A total of 429 adults with pharmacoresistant epilepsy completed the Boston Naming Test (BNT) and Memory Assessment Clinics Self-Rating Scale (MAC-S) before and after resective surgery. Multiple regression analyses were used to examine the relationship between objective naming decline and subjective language functioning, while controlling for the confounding effect of depression. RESULTS: Individuals who experienced moderate to severe naming decline (≥11 raw points on BNT) following surgery reported a decline in subjective language functioning (p < .001) and endorsed problems with word-retrieval as well as more general semantic abilities. Those who experienced mild naming decline (5-10 raw points) also reported an increase in subjective language problems (p = .006). Complaints in this group were less severe than in those with more marked naming declines and were primarily related to word-retrieval. Both of these relationships remained significant after controlling for the confounding effect of depression (p < .005-.014). CONCLUSIONS: Individuals with epilepsy who experience naming decline following surgery perceive these declines in their daily life, regardless of whether or not they are depressed. Findings support the utilization of risk models to predict naming outcome and the importance of counseling patients regarding the risk for naming decline following surgery.

A retrospective, population-based cohort study of driving under the influence, Alzheimer's disease diagnosis, and survival.

ABSTRACTIntroduction:The relationship between Alzheimer's Disease (AD) and alcohol addiction is poorly characterized. Arrests for driving under the influence (DUI) can serve as a proxy for alcohol addiction. Therefore, the potential association between DUI and AD could be helpful in understanding the relationship between alcohol abuse and AD. MATERIALS AND METHODS: A retrospective, population-based cohort study using state health and law enforcement data was performed. The study cross-referenced 141,281 South Carolina Alzheimer's Disease Registry cases with state law enforcement data. RESULTS: Of the 2,882 registry cases (1.4%) found to have a history of at least one DUI arrest, cases were predominantly White (58.7%) and male (77.4%). Results showed a correlation coefficient of 0.7 (p < 0.0001) between the age of first DUI arrest and the age of AD diagnosis. A dose-response relationship between the number of DUIs and age of AD onset was found to exist, where those with a history of DUI arrest were diagnosed an average of 9.1 years earlier, with a further 1.8 years earlier age at diagnosis in those with two or more arrests for DUI. A history of DUI arrest was also found to be negatively associated with survival after diagnosis, with a 10% decreased life expectancy in those with a DUI arrest history. CONCLUSIONS: Driving under the influence, a potential indicator of alcohol addiction, is associated with an earlier onset of AD registry diagnosis and shortened survival after diagnosis. This study contributes to the growing body of evidence suggesting that some cases of AD are alcohol related and, possibly, postponable or preventable.

Remission after complete excision of an intramedullary hemangioma with an identifiable tumor plane in a dog.

OBJECTIVE: To describe the use of an identifiable tumor plane (ITP) during myelotomy to excise an intramedullary hemangioma in a dog and report the outcome. STUDY DESIGN: Case report. ANIMALS: One 5.5-year-old 42.9-kg spayed female Leonberger dog. METHODS: Clinical signs included progressive proprioceptive deficits of both pelvic limbs. Magnetic resonance imaging was consistent with a dorsal intramedullary mass at L3-L4. A laminectomy of the third and fourth lumbar vertebrae provided access for dorsal myelotomy. A clear surgical ITP was identified between the intramedullary mass and the spinal cord facilitating complete surgical resection. RESULTS: Histopathological examination was consistent with a hemangioma. Postoperative MRI was consistent with complete excision of the mass. No evidence of recurrence was found by MRI at 3 months and at 22 months after surgery. Mild proprioceptive deficits persisted in the right pelvic limb. CONCLUSION: A clear ITP was present, and gross-total resection (GTR) was achieved without significant morbidity. Persistent clinical remission resulted from surgery as the sole therapy. CLINICAL SIGNIFICANCE: For an intramedullary tumor, GTR is the absence of visible tumor on intraoperative inspection combined with the absence of intramedullary contrast enhancement on postoperative MRI. When an ITP is present, GTR and resultant long-term remission may be more likely.

Immunologic and gene expression profiles of spontaneous canine oligodendrogliomas.

Malignant glioma (MG), the most common primary brain tumor in adults, is extremely aggressive and uniformly fatal. Several treatment strategies have shown significant preclinical promise in murine models of glioma; however, none have produced meaningful clinical responses in human patients. We hypothesize that introduction of an additional preclinical animal model better approximating the complexity of human MG, particularly in interactions with host immune responses, will bridge the existing gap between these two stages of testing. Here, we characterize the immunologic landscape and gene expression profiles of spontaneous canine glioma and evaluate its potential for serving as such a translational model. RNA in situ hybridization, flowcytometry, and RNA sequencing were used to evaluate immune cell presence and gene expression in healthy and glioma-bearing canines. Similar to human MGs, canine gliomas demonstrated increased intratumoral immune cell infiltration (CD4+, CD8+ and CD4+Foxp3+ T cells). The peripheral blood of glioma-bearing dogs also contained a relatively greater proportion of CD4+Foxp3+ regulatory T cells and plasmacytoid dendritic cells. Tumors were strongly positive for PD-L1 expression and glioma-bearing animals also possessed a greater proportion of immune cells expressing the immune checkpoint receptors CTLA-4 and PD-1. Analysis of differentially expressed genes in our canine populations revealed several genetic changes paralleling those known to occur in human disease. Naturally occurring canine glioma has many characteristics closely resembling human disease, particularly with respect to genetic dysregulation and host immune responses to tumors, supporting its use as a translational model in the preclinical testing of prospective anti-glioma therapies proven successful in murine studies.