High Mitochondrial Haplotype Diversity Found in Three Pre-Hispanic Groups from Colombia.

The analysis of mitochondrial DNA (mtDNA) hypervariable region (HVR) sequence data from ancient human remains provides valuable insights into the genetic structure and population dynamics of ancient populations. mtDNA is particularly useful in studying ancient populations, because it is maternally inherited and has a higher mutation rate compared to nuclear DNA. To determine the genetic structure of three Colombian pre-Hispanic populations and compare them with current populations, we determined the haplotypes from human bone remains by sequencing several mitochondrial DNA segments. A wide variety of mitochondrial polymorphisms were obtained from 33 samples. Our results support a high population heterogeneity among pre-Hispanic populations in Colombia.

Genotyping by Sequencing for SNP-Based Linkage Analysis and the Development of KASPar Markers for Male Sterility and Polyembryony in Citrus.

Polyembryony and male sterility (MS) are essential characters for citrus breeding. MS, coupled with parthenocarpy, allows for addressing the diversification of diploid seedless mandarin varieties, and nucleocytoplasmic MS is the most prevalent system. Polyembryony limits the use of seed parents in scion breeding programs, and the recovery of monoembryonic hybrids to be used as female parents is a crucial pre-breeding component. The objectives of this work were the identification of SNPs closely linked with the genes implied in these traits for marker-assisted selection. Genotyping by sequencing was used to genotype 61 diploid hybrids from an F1 progeny recovered from crossing 'Kiyomi' and 'Murcott' tangors. A total of 6444 segregating markers were identified and used to establish the two parental genetic maps. They consisted of 1374 and 697 markers encompassing 1416.287 and 1339.735 cM for 'Kiyomi' and 'Murcott', respectively. Phenotyping for MS and polyembryony was performed. The genotype-trait association study identified a genomic region on LG8 which was significantly associated with MS, and a genomic region on LG1 which was significantly associated with polyembryony. Annotation of the identified region for MS revealed 19 candidate genes. One SNP KASPar marker was developed and fully validated for each trait.

Application of mixture distributions for identifying thresholds of frequent and high inpatient mental health service use in longitudinal data.

BACKGROUND: There is a need for greater understanding about frequent and high use of inpatient mental health services, and those with ongoing increased needs. Most studies employ a threshold of frequent use (e.g. numbers of admissions) and high use (e.g. lengthy stays) without justification. AIMS: To identify model-driven thresholds for frequent/high inpatient mental health service use and contrast characteristics of patients identified using various models and thresholds. METHOD: Retrospective population-based study using 12 years of longitudinal data for 5631 patients admitted with a mental health diagnosis. Two-component negative binomial and poisson mixture (truncated/untruncated) models identified thresholds for frequent/high use in a 12-month period. RESULTS: The two-component negative binomial mixture model resulted in the best model fit. Using negative binomial-derived thresholds, 5.3% of patients had a period of frequent use (admitted six or more times), 15.8% of high use (hospitalised for 45 or more days) and 3.5% of heavy use (both frequent and high use). The prevalence of specific mental health disorders (e.g. mood disorder and schizophrenia) among frequent and high use cohorts varied across thresholds. CONCLUSIONS: This model-driven approach can be applied to identify thresholds in other cohorts. Threshold choice may depend on the magnitude and focus of potential interventions.

Match Injuries in the Spanish Rugby Union Division de Honor.

OBJECTIVE: To describe the injury rate, severity, cause, anatomical location (tissue damaged), recurrence, place and time during matches throughout a season in the Spanish Rugby Union Division de Honor. METHODS: Observational, prospective and descriptive study conducted in the competition of the Spanish División de Honor de Rugby with 258 players. The data were reported by the medical services of the previously formed clubs. RESULTS: Total exposure was 4100 h, during which 220 injuries occurred. The average number of sick days was 36.8. The total injury rate was 53.6 injuries/1000 h of exposure. Three quarters suffered 93 injuries and the forwards sustained a total of 127 injuries, with a total of 48.6 and 58.1 injuries/1000 h of exposure, respectively. Moderate injuries were the most frequent. Specifically, ligament injury was the most frequent, and dislocation was the injury that caused the most sick days. The most injuries occurred in the third quarter of the match, and the most serious injuries occurred in the second quarter. CONCLUSIONS: The injury rate of Spanish rugby competitors is 53.6 injuries/1000 match hours, with an average of 36.8 sick days. Contact injuries are the most frequent, taking place especially when tackling or being tackled.

A Functional Assessment Tool to Distinguish Controls From Alzheimer's Disease in Lima, Peru.

BACKGROUND: The Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale is a versatile functional assessment tool for patients with Alzheimer's disease (ad). We evaluated its performance in controls, Peruvians with MCI or AD. METHODS: A cross-sectional study of older adults attending a neurology institute in Lima (Peru) with mild cognitive impairment (MCI), ad or cognitively healthy. Test-retest reliability (intraclass correlation coefficient, ICC; internal consistency, Cronbach's alpha) and validity were assessed. RESULTS: We enrolled 276 individuals (ad: 113, MCI: 68, controls: 95) with no age, sex, educational level, and depressive symptom differences. Reliability was ideal (ICC: .996), and Cronbach's alpha was adequate (.937). The ADCS-ADL could not differentiate MCI from controls but did differentiate ad severity. The ADCS-ADL correlated highly with nearly all tools. CONCLUSIONS: The ADCS-ADL scale is reliable in a population with ad in Lima, Peru. Future work may validate a tool for Peruvians with lower educational levels.

How to streamline the low and negligible research ethics and governance review process from 80 to 10 days: submission to decision.

Most clinicians find research ethics and governance difficult and time consuming. This study aimed to develop a better local review process for low-risk research. We used real-time processing, leveraged local expertise and streamlined paperwork. As a result, turnaround times decreased from more than 80 days to 10 days, creating an efficient review process for low-risk projects.

Integrative Clinical, Radiological, and Molecular Analysis for Predicting Remission and Recurrence of Cushing Disease.

CONTEXT: Adrenocorticotropin (ACTH)-secreting pituitary tumors (ACTHomas) are associated with severe comorbidities and increased mortality. Current treatments mainly focus on remission and prevention of persistent disease and recurrence. However, there are still no useful biomarkers to accurately predict the clinical outcome after surgery, long-term remission, or disease relapse. OBJECTIVES: This work aimed to identify clinical, biochemical, and molecular markers for predicting long-term clinical outcome and remission in ACTHomas. METHODS: A retrospective multicenter study was performed with 60 ACTHomas patients diagnosed between 2004 and 2018 with at least 2 years' follow-up. Clinical/biochemical variables were evaluated yearly. Molecular expression profile of the somatostatin/ghrelin/dopamine regulatory systems components and of key pituitary factors and proliferation markers were evaluated in tumor samples after the first surgery. RESULTS: Clinical variables including tumor size, time until diagnosis/first surgery, serum prolactin, and postsurgery cortisol levels were associated with tumor remission and relapsed disease. The molecular markers analyzed were distinctly expressed in ACTHomas, with some components (ie, SSTR1, CRHR1, and MKI67) showing instructive associations with recurrence and/or remission. Notably, an integrative model including selected clinical variables (tumor size/postsurgery serum cortisol), and molecular markers (SSTR1/CRHR1) can accurately predict the clinical evolution and remission of patients with ACTHomas, generating a receiver operating characteristic curve with an area under the curve of 1 (P < .001). CONCLUSION: This study demonstrates that the combination of a set of clinical and molecular biomarkers in ACTHomas is able to accurately predict the clinical evolution and remission of patients. Consequently, the postsurgery molecular profile represents a valuable tool for clinical evaluation and follow-up of patients with ACTHomas.

Evaluation of the geriatrician in the practice model of care for dementia assessment and management in rural Australia.

OBJECTIVES: To evaluate an integrated care program expanding the physician in the practice model into geriatrics, focussing on dementia assessment and management. DESIGN: Observational descriptive study. SETTING: The rural section of a local health district in New South Wales, Australia. PARTICIPANTS: Patients attending eight general practices, in addition to practice nurses and general practitioners. INTERVENTIONS: Self-report questionnaires completed by patients, specialist general practitioners and practice nurses. Responses to open-ended questions were analysed using content analysis. Routinely collected health data of patients who took part in the program were compared with data of patients from the same institution who did not take part in the program. MAIN OUTCOME MEASURES: A number of planned reviews, actual reviews and emergency department presentations for participating patients, self-efficacy amongst general practitioners and practice nurses, and patient satisfaction and comfort levels. RESULTS: The GIP program was well received by most patients, GPs and practice nurses. Almost 90% of patients found it easier to see the specialist at their general practice. They were less likely to have planned reviews, actual reviews and emergency department presentations than patients who did not take part in the program. GPs and practice nurses expressed increased confidence in and knowledge of dementia assessment and management. CONCLUSIONS: Dementia assessment and management programs based on the physician in the practice model may be well received in similar rural settings. Larger prospective studies are needed to further examine the relationship between programs and patients' health outcomes.

Diagnostic accuracy of brief cognitive screening tools to diagnose vascular cognitive impairment in Peru.

INTRODUCTION: To evaluate the diagnostic accuracy of three brief cognitive screening (BCS) tools, Peruvian version of Addenbrooke's Cognitive Examination (ACE-Pe), of INECO Frontal Screening (IFS-Pe) and of the Mini-Mental State Examination (MMSE-Pe), for the diagnosis of vascular cognitive impairment (VCI) and its non-dementia stages (VCI-ND) and vascular dementia (VD) in patients with cerebral stroke in Lima-Peru. MATERIALS AND METHODS: A cohort analysis to evaluate the diagnostic accuracy of three BCS for VCI. RESULTS: Two hundred and four patients were evaluated: 61% Non-VCI, 30% VCI-ND and 9% VD. To discriminate patients with VCI from controls, the area under the curve (AUC) of ACE-Pe, IFS-Pe and MMs-Pe were 0.99 (95% confidence interval [CI] 0.98-0.99), 0.99 (95%CI 0.98-0.99) and 0.87 (95%CI 0.82-0.92), respectively. Of the three BCS, the IFS-Pe presented a larger AUC to discriminate VCI-ND from VD (AUC = 0.98 [95%CI 0.95-1]) compared to ACE-Pe (AUC = 0.84 [95%CI 0.74-0.95]) and MMSE-Pe (0.92 [95%CI 0.86-0.99]). The IFS-Pe presented a higher sensitivity (S), specificity (Sp), and positive (+LR) and negative likelihood ratios (-LR) (S = 96.72%, Sp = 89.47%, +LR = 9.1 and -LR = 0.03) than ACE-Pe (S = 96.72%, Sp = 63.16%, +LR = 2.62 and -LR = 0.05) and MMSE-Pe (S = 90.16%, Sp = 78.95%, +LR = 4.28 and -LR = 0.12). In the multiple regression analysis, the IFS-Pe was not affected by age, sex or years of schooling. CONCLUSION: The IFS-Pe has the best diagnostic accuracy for detecting VCI and discriminating between pre-dementia (VCI-ND) and dementia (VD) stages.

Penicillin versus anti-staphylococcal beta-lactams for penicillin-susceptible Staphylococcus aureus blood stream infections: a retrospective cohort study.

The objective of the study is to assess the efficacy and tolerability of penicillins compared to anti-staphylococcal beta-lactams for treatment of penicillin-susceptible Staphylococcus aureus bloodstream infections (PSSA BSI). A retrospective cohort study was conducted of 140 sequential PSSA BSI presenting to a local health district (90 cases included). Penicillin susceptibility was confirmed by disc diffusion, Vitek® and Nitrocefin beta-lactamase methods. Clinical information regarding comorbidities and infection complexity was recorded. Antibiotic choice, dosage and duration were reviewed. Outcomes were compared according to the definitive treatment with either penicillin or ASBLs. The primary outcome was 30-day mortality. Secondary outcomes included renal injury, microbiological relapse and treatment tolerability. Ninety patients met inclusion criteria and were included in subsequent analysis. Of PSSA BSI, 69% were community acquired. Eighty-two percent had complex PSSA infections. The average duration of bacteraemia was 2.8 days (SD = 1.8 days). Sixty-six patients received definitive penicillin treatment, with a mean of 3.5 days of empiric antibiotics prior to penicillin. Twenty-four patients received definitive ASBL treatment (11 cefazolin, 13 flucloxacillin). There was no difference in 30-day mortality between groups (p = 1). There was no difference in renal injury (p > 0.5), hospital length of stay (p = 0.59) or microbiological relapse within 1 year (p = 0.17). Penicillin treatment was well tolerated. Our data supports penicillin as a suitable and well-tolerated alternative to ASBL in managing complex PSSA BSI.

Outcomes of COVID-19 in the community: A prospective cohort study.

BACKGROUND AND OBJECTIVES: The literature indicates that patients who had previously had COVID-19 are reporting ongoing symptoms. The objective of this study was to examine ongoing symptoms, functional limitations and quality of life over time in a cohort of individuals who were deemed to have recovered. METHOD: This was a prospective observational study on biopsychosocial outcomes at enrolment and again one month later. RESULTS: In a cohort of 59 participants, ongoing symptoms were reported by 73% at 4.5 months (standard deviation = 1.4) post diagnosis, with 45% reporting difficulty with pre-illness activities of daily living. Of the 52 participants who completed the follow-up survey (mean 5.6 months post diagnosis), 42% reported ongoing symptoms, lower physical quality of life (12-Item Short Form Health Survey) and higher levels of anxiety, depression and stress (Depression, Anxiety and Stress Scale). DISCUSSION: Ongoing symptoms such as fatigue, pain and limb weakness as well as functional impairment post initial diagnosis were common. Improved understanding of this cohort can assist general practitioners in providing care.

Social Cognition and Behavioral Assessments Improve the Diagnosis of Behavioral Variant of Frontotemporal Dementia in Older Peruvians With Low Educational Levels.

Background: The behavioral variant of frontotemporal dementia (bvFTD), characterized by early behavioral abnormalities and late memory impairment, is a neurodegenerative disorder with a detrimental impact on patients and their caregivers. bvFTD is often difficult to distinguish from other neurodegenerative diseases, such as Alzheimer's disease (AD), using brief cognitive tests. Combining brief socio-cognitive and behavioral evaluations with standard cognitive testing could better discriminate bvFTD from AD patients. We sought to evaluate the diagnostic accuracy of brief socio-cognitive tests that may differentiate bvFTD and AD patients with low educational levels. Methods: A prospective study was performed on 51 individuals over the age of 50 with low educational levels, with bvFTD or AD diagnosed using published criteria, and who were receiving neurological care at a multidisciplinary neurology clinic in Lima, Peru, between July 2017 and December 2020. All patients had a comprehensive neurological evaluation, including a full neurocognitive battery and brief tests of cognition (Addenbrooke's Cognitive Examination version III, ACE-III), social cognition (Mini-social Cognition and Emotional Assessment, Mini-SEA), and behavioral assessments (Frontal Behavioral Inventory, FBI; Interpersonal Reactivity Index-Emphatic Concern, IRI-EC; IRI-Perspective Taking, IRI-PT; and Self-Monitoring Scale-revised version, r-SMS). Receiver operating characteristic (ROC) analysis to calculate the area under the curve (AUC) was performed to compare the brief screening tests individually and combined to the gold standard of bvFTD and AD diagnoses. Results: The AD group was significantly older than the bvFTD group (p < 0.001). An analysis of the discriminatory ability of the ACE-III to distinguish between patients with AD and bvFTD (AUC = 0.85) and the INECO Frontal Screening (IFS; AUC = 0.78) shows that the former has greater discriminatory ability. Social and behavioral cognition tasks were able to appropriately discriminate bvFTD from AD. The Mini-SEA had high sensitivity and high moderate specificity (83%) for discriminating bvFTD from AD, which increased when combined with the brief screening tests ACE-III and IFS. The FBI was ideal with high sensitivity (83%), as well as the IRI-EC and IRI-PT that also were adequate for distinguishing bvFTD from AD. Conclusions: Our study supports the integration of socio-behavioral measures to the standard global cognitive and social cognition measures utilized for screening for bvFTD in a population with low levels of education.

Performance of the Rowland Universal Dementia Assessment Scale for the Detection of Mild Cognitive Impairment and Dementia in a Diverse Cohort of Illiterate Persons From Rural Communities in Peru.

Background: The accurate diagnosis of neurocognitive disorders in illiterate Peruvian populations is challenging, largely owing to scarcity of brief cognitive screening tools (BCST) validated in these diverse populations. The Peruvian version of the Rowland Universal Dementia Assessment Scale (RUDAS-PE) is a BCST that relies minimally on educational attainment and has shown good diagnostic accuracy in an urban illiterate population in Peru, yet its psychometric properties in illiterate populations in rural settings of the country have not been previously investigated. Objectives: To establish the diagnostic accuracy of the RUDAS-PE compared to expert clinical diagnosis using the Clinical Dementia Rating (CDR) Scale in healthy and cognitively impaired illiterate persons living in two culturally and geographically distinct rural communities of Peru. Methods: A cross-sectional, population-based study of residents ≥ 50 years of age living in the Peruvian rural communities of Santa Clotilde and Chuquibambilla. A total of 129 subjects (76 from Santa Clotilde and 53 from Chuquibambilla) were included in this study. Gold standard diagnostic neurocognitive evaluation was based on expert neurological history and examination and administration of the CDR. Receiver operating characteristics, areas under the curve (AUC), and logistic regression analyses were conducted to determine the performance of RUDAS-PE compared to expert gold standard diagnosis. Results: Compared to gold standard diagnosis, the RUDAS-PE was better at correctly discriminating between MCI and dementia than discriminating between MCI and controls in both sites (97.0% vs. 76.2% correct classification in Chuquibambilla; 90.0% vs. 64.7% in Santa Clotilde). In Chuquibambilla, the area under the curve (AUC) of the RUDAS to discriminate between dementia and MCI was 99.4% (optimal cutoff at <18), whereas between MCI and controls it was 82.8% (optimal cutoff at <22). In Santa Clotilde, the area under the curve (AUC) of the RUDAS to discriminate between dementia and MCI was 99.1% (optimal cutoff at <17), whereas between MCI and controls it was 75.5% (optimal cutoff at <21). Conclusions: The RUDAS-PE has acceptable psychometric properties and performed well in its ability to discriminate MCI and dementia in two cohorts of illiterate older adults from two distinct rural Peruvian communities.

Increasing use of intraoperative cholangiogram in Australia: is it evidence-based?

BACKGROUND: The role of routine intraoperative cholangiograms (IOCs) for prevention of bile duct injury (BDI) is contentious. There are recent reports of limited utility of IOC in preventing BDI. In Australia, IOCs are used more frequently than internationally. This study aimed to evaluate the rate of IOC use in Australia and explore potential changes in practice in light of evolving evidence for the utility of IOC. METHODS: Data were collated using service item numbers in Medicare Benefits Scheme records on the Australian Government Medicare website, for services claimed between 1 January 2001 and 31 December 2019. These data were used to analyse trends in rates of IOC, cholecystectomy and BDI repair. Data were age-standardized to account for changes in the population over time. RESULTS: The number of IOCs claimed increased by 31.8% and cholecystectomies by 7.0% over the study period. Age-standardized service rates per 100 000 persons increased by 5.5 and 32.6, respectively. Rates of IOC per 100 000 cholecystectomies steadily increased across the study period, while BDI repair rates remained low and erratic. CONCLUSION: Increasing use of IOC over the last 20 years reflects a trend towards routine rather than selective IOC; however, there is little discernible change in the number of BDIs requiring repair procedures. This suggests that routine IOC use to prevent or minimize BDI is unwarranted. Further investigation is required into the selective IOC use in high-risk patients rather than mandatory use in all patients.

New-onset acute rapidly deteriorating case of calciphylaxis after open heart surgery: a case report.

BACKGROUND: Calciphylaxis is a rare life-threatening condition that is characterized by calcification of small blood vessels and soft tissues. This condition is classically described in uraemic patients with end-stage renal failure who are on dialysis or had previous renal transplant. It has also been reported in non-uraemic patients and those who are on warfarin therapy. It is typically associated with high calcium/phosphorus product. Patients classically present with painful skin lesion that evolve into painful ulcers. There are multiple risk factors that were reported to trigger or worsen calciphylaxis. Treatment is a multidisciplinary approach that involves elimination of risk factors, wound management, pain control, and optimization of calcium/phosphorus metabolism. Reported mortality rates are very high especially in the uraemic group. CASE SUMMARY: Here we present a case of a patient, who is on chronic renal dialysis for stage renal failure, who underwent mechanical mitral valve replacement and tricuspid valve repair. In the perioperative period, she was exposed to multiple risk factors that are known to potentially trigger prophylaxis. In the early postoperative period, she developed new-onset rapidly deteriorating skin lesions and the histopathological diagnosis confirmed calciphylaxis. Her treatment plan included pain control, frequent wound care, and optimization of nutritional and metabolic status. DISCUSSION: Calciphylaxis is a very serious condition that is usually associated with poor outcome. In this case, we discuss the unusual presentation of this condition with particular emphasis on the multiple perioperative risk factors that can potentially trigger the onset of calciphylaxis in postoperative cardiac patients. We also discuss the epidemiology, pathogenesis, diagnosis, histopathological findings, and different lines of treatment of this serious condition and the potential preventative strategies.

Predisposing, enabling and need factors associated with increased use and ongoing increased use of inpatient mental health care: A population-based longitudinal study.

OBJECTIVE: The study investigated factors associated with frequent (admissions), high (total length of stay) or heavy (frequent and high) hospital use, and with ongoing increased hospital use, for mental health conditions in a regional health district. METHODS: A retrospective population-based study using longitudinal hospital, emergency department and community service use data for people admitted with a mental health condition between 1 January 2012 and 31 December 2016. Multivariate logistic regression models assessed the association of predisposing, enabling and need factors with increased, and ongoing increased, hospital use. RESULTS: A total of 5,631 people had at least one mental health admission. Frequent admission was associated with not being married (odds ratio = 2.3, 95% confidence interval = [1.5, 3.3]), no private hospital insurance (odds ratio = 2.2, 95% confidence interval = [1.2, 3.8]), previous mental health service use (community, emergency department, lengthy admissions) and a history of a substance use disorder, childhood trauma, self-harm or chronic obstructive pulmonary disease. High and heavy hospital use was associated with marital status, hospital insurance, admission for schizophrenia, previous mental health service use and a history of self-harm. Ongoing frequent use was less likely among those aged 65 and older (odds ratio = 0.2, 95% confidence interval = [0.1, 1.0]) but more likely among those with a history of depression (odds ratio = 2.2, 95% confidence interval = [1.1, 4.4]). Ongoing high use was also associated with admissions for schizophrenia and a history of self-harm. CONCLUSION: Interventions targeted at younger people hospitalised with schizophrenia, a history of depression or self-harm, particularly with evidence of social and or health disadvantage, should be considered to improve long-term consumer and health system outcomes. These data can support policymakers to better understand the context and need for improvements in stepped or staged care for people frequently using inpatient mental health care.

Critical adjustments in a department of orthopaedics through the COVID-19 pandemic.

PURPOSE: SARS-CoV-2's new scenario has forced health systems to work under extreme stress urging to perform a complete reorganization of the way our means and activities were organized. The orthopaedic and trauma units have rescheduled their activities to help SARS-CoV-2 units, but trauma patients require also treatment, and no standardized protocols have been established. METHODS: A single-centre cross-sectional study was performed in a tertiary hospital. Two different periods of time were analyzed: a two week period of time in March 2019 (pre-SARS-CoV-2) and the same period in March 2020 (SARS-CoV-2 pandemic time). Outpatient's data, emergency activity, surgical procedures, and admissions were evaluated. Surgeons' and patient's opinion was also evaluated using a survey. RESULTS: A total of ~ 16k (15,953) patients were evaluated. Scheduled clinical appointments decreased by ~ 22%. Urgent consultations and discharge from clinics also descended (~ 37% and ~ 20% respectively). Telemedicine was used in 90% of outpatient clinical evaluations. No elective surgical procedures during SARS-CoV-2 time were scheduled, and subtracting the effect of elective surgeries, there was a reduction of inpatient surgeries, from ~ 85% to ~ 59%. Patients delayed trauma assistance more than 48 hours in 13 cases (35%). Pre-operative admission for hip fractures decreased in ten hours on average. Finally, surveys stated that patients were more in favour than surgeons were to this new way to evaluate orthopaedic and trauma patients based strongly on telemedicine. CONCLUSION: Detailed protocols should be standardized for surgical departments during the pandemic. This paper offers a general view in how this virus affects an orthopaedic unit and could serve as a protocol and example for orthopaedic and trauma units. Even in the worst scenario, an orthopaedic and trauma unit could offer an effective, efficient, and quality service. SARS-CoV-2 will set up a new paradigm for health care in orthopaedics and trauma.

Analysis of Crossover Events and Allele Segregation Distortion in Interspecific Citrus Hybrids by Single Pollen Genotyping.

In citrus, a classical method of studying crossovers and segregation distortion (SD) is the genetic analysis of progenies. A new strategy combining fluorescence-activated cell sorting and whole genome amplification of haploid pollen nuclei with a large set of molecular markers, offers the opportunity to efficiently determine the frequency of crossovers and the identification of SD without the need to generate segregating populations. Here we have analyzed meiotic crossover events in a pollen nuclei population from "Eureka" lemon and the allelic SD was evaluated in a pollen nuclei population from a clementine × sweet orange hybrid ("CSO"). Data obtained from the "CSO" pollen nuclei population were compared to those obtained from genotyping of a segregating population ("RTSO") arising from a hand-made sexual hybridization between diploid non apomictic selected tangor (mandarin × sweet orange; "RTO" tangor) as female parent pollinated with "CSO" tangor as male parent. The analysis of crossovers rates on chromosome 1 revealed the presence of up to five crossovers events on one arm and four on the corresponding other arm, with an average of 1.97 crossovers per chromosome while no crossover events were observed in five "Eureka" lemon pollen nuclei. The rate of SD observed in "CSO" pollen nuclei (13.8%) was slightly lower than that recovered in the "RTSO" population (20.7%). In the pollen nuclei population, SD was found on linkage group (LG) 2, while the "RTSO" population showed SD on LGs 2 and 7. Potential male gametic selection mechanisms were distinguished in pollen grains, while in the population, mechanisms of gametophytic selection and/or zygotic selection were observed. This methodology is a very useful tool to facilitate research focused on the reproductive biology of citrus and study the mechanisms that affect crossovers and SD.

Validation of the RUDAS for the Identification of Dementia in Illiterate and Low-Educated Older Adults in Lima, Peru.

Objectives: To evaluate the performance of the Peruvian version of the Rowland Universal Dementia Assessment Scale (RUDAS-PE) in discriminating between controls and patients with mild cognitive impairment (MCI) and dementia in an illiterate population with low-levels of education. Methods: We compared the cognitive performance of 187 elderly subjects who were illiterate (controls n = 60; MCI n = 64; dementia n = 63). Neuropsychological measures included the RUDAS-PE, Mini-Mental State Examination (MMSE), INECO Frontal Screening (IFS), and Pfeffer Functional Activities Questionnaire (PFAQ). The results were compared to a neuropsychological evaluation (gold standard), including use of Clinical Dementia Rating (CDR) scores. Results: We found a Cronbach's alpha was 0.65; Spearman's correlation coefficient was 0.79 (p < 0.01). The area under the receiver operating characteristics curve for the RUDAS to discriminate dementia from MCI was 98.0% with an optimal cut-off <19 (sensitivity 95%, specificity 97%); whereas, to differentiate MCI and controls was 98.0% with an optimal cut-off <23 (sensitivity 89%, specificity 93%). Conclusions: Based on its excellent psychometric properties, we find the RUDAS-PE suitable to aid in the opportune detection of dementia in a geriatric illiterate population with low-levels of education.

A key 'foxy' aroma gene is regulated by homology-induced promoter indels in the iconic juice grape 'Concord'.

'Concord', the most well-known juice grape with a parentage of the North American grape species Vitis labrusca L., possesses a special 'foxy' aroma predominantly resulted from the accumulation of methyl anthranilate (MA) in berries. This aroma, however, is often perceived as an undesirable attribute by wine consumers and rarely noticeable in the common table and wine grape species V. vinifera. Here we discovered homology-induced promoter indels as a major genetic mechanism for species-specific regulation of a key 'foxy' aroma gene, anthraniloyl-CoA:methanol acyltransferase (AMAT), that is responsible for MA biosynthesis. We found the absence of a 426-bp and/or a 42-bp sequence in AMAT promoters highly associated with high levels of AMAT expression and MA accumulation in 'Concord' and other V. labrusca-derived grapes. These promoter variants, all with direct and inverted repeats, were further confirmed in more than 1,300 Vitis germplasm. Moreover, functional impact of these indels was validated in transgenic Arabidopsis. Superimposed on the promoter regulation, large structural changes including exonic insertion of a retrotransposon were present at the AMAT locus in some V. vinifera grapes. Elucidation of the AMAT genetic regulation advances our understanding of the 'foxy' aroma trait and makes it genetically trackable and amenable in grapevine breeding.