Measuring ART Adherence Among Young Adults with Perinatally Acquired HIV: Comparison Between Self-report, Telephone-Based Pill Count, and Objective Pharmacologic Measures.

Tenofovir diphosphate (TVF-DP) can be quantified in red blood cells (RBCs) and dried blood spots (DBS) and can objectively measure ART adherence and predict viral suppression. Data on the association of TFV-DP with viral load are very limited in adolescents and young adults (AYA) living with perinatally-acquired HIV (PHIV), as are data comparing TFV-DP to other measures of ART adherence, such as self-report and unannounced telephone pill count. Viral load and ART adherence (self-report, TFV-DP and unannounced telephone pill count) were assessed and compared among 61 AYAPHIV recruited from an ongoing longitudinal study (CASAH) in New York City.

Tenofovir diphosphate in dried blood spots and HIV-1 resistance in South Africa.

BACKGROUND: Suboptimal antiretroviral (ART) adherence can lead to virologic failure with consequent HIV-1 resistance. Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is a powerful biomarker of cumulative adherence, predictive of future viremia. It has been associated with resistance in Persons With HIV (PWH) in South Africa and the US. We explored the relationship of TFV-DP concentrations with antiretroviral drug resistance at the time of treatment failure in SA. METHODS: Adult PWH from health clinics in Cape Town, South Africa on efavirenz-based first-line ART containing tenofovir disoproxil fumarate (TDF) with an undetectable (< 50 copies/mL) HIV-1 viral load (VL) were prospectively enrolled in an observational cohort for 12 months. Monthly study visits included blood collection for HIV-1 VL and DBS for TFV-DP. The first confirmed viral breakthrough (VB) > 400 copies/mL triggered HIV-1 genotyping at the subsequent visit. An electronic adherence (EA) device monitored ART adherence in real-time, estimated as a percent for the 30-days prior to VB. Wilcoxon rank sum test was used to compare median [IQR] TFV-DP by genotype outcome. RESULTS: Of 250 individuals, (n = 195, 78% women), 21 experienced VB, with a median of 5 [4;7] months on study, and a median EA of 33.3 [13.3;53.3]%. Demographic characteristics between those with and without VB were similar. Median VL at VB was 4.0 [3.2;4.5] log copies/mL. TFV-DP concentrations trended down towards the VB visit. Median TFV-DP concentrations were significantly higher in those HIV-1 genotype did not amplify due to being virally suppressed at the subsequent visit (n = 10; 380 [227-661] fmol/punch, p = 0.035; EA 45 [24.9; 59.2]%); than in those who were successfully genotyped with evidence of drug resistance (n = 5, 241 [150-247] fmol/punch, EA 20 [6.7;36.7]%) and in individuals who did not have resistance (n = 3, 39.9 [16.6; 93.9] fmol/punch; EA 33.3 [16-38]%). Three genotype collections were not done. Only non-nucleoside reverse transcriptase inhibitor-associated mutations were identified on resistance testing. (K103N, E138K, Y118H). CONCLUSION: TFV-DP in DBS showed a step-wise inverse relationship with VB and drug resistance, with evidence of low cumulative ART adherence in PWH who developed antiretroviral resistance. Monitoring TFV-DP concentrations could be a valuable tool for predicting future VB and future resistance.

Identification of genomic loci conferring broad-spectrum resistance to multiple nematode species in exotic soybean accession PI 567305.

KEY MESSAGE: Genetic analysis identified a unique combination of major QTL for resistance to important soybean nematodes concurrently present in a single soybean accession, which has not been reported earlier. An exotic soybean [Glycine max (L.) Merr.] accession, PI 567305, was reported to be highly resistant to three important nematode species, soybean cyst (SCN), root-knot (RKN), and reniform (RN) nematodes. However, genetic basis controlling broad-spectrum resistance in this germplasm has not been investigated. We report results of genetic analysis to identify genomic loci conferring resistance to these nematode species. A bi-parental population consisting of 242 F8-derived recombinant inbred lines (RILs) was developed from a cross of a nematode susceptible cultivar, Magellan, and resistant accession, PI 567305. The RILs were phenotyped for nematode resistance to three SCN HG types. They were genotyped using the Infinium SoySNP6K BeadChips and genotype-by-sequencing (GBS) methods in an attempt to evaluate the cost-effectiveness and efficiency of these two genotyping platforms. Genetic analysis confirmed the major QTL on chromosomes (Chrs) 10 and 18 with broad-spectrum resistance to the three nematodes present in this germplasm. Haplotype and copy number variation analyses of SCN resistance QTL indicated that PI 567305 has a different haplotype, which is associated with likely a unique SCN resistance mechanism different from Peking- or PI 88788-type resistance. The evaluations of both Infinium Beadchip- and GBS-based genotyping technologies provided comprehensive insights for researchers to choose a cost-effective and efficient platform for QTL mapping and for other genomic studies in soybeans.

The Impact of HIV-Associated Neurocognitive Impairment on Driving Performance in Commercial Truck Drivers.

Driving ability can be diminished amongst people with HIV with associated neurocognitive impairment (NCI). We explore the relationship between HIV status, NCI and driving ability in professional truck drivers. Forty male professional drivers (20 HIV-positive; mean age = 39.20 ± 7.05) completed a neuropsychological test battery, two driving simulator tasks that assessed driving ability, and a driving history and habits questionnaire. A higher proportion of HIV-positive drivers exhibited impaired overall cognitive performance (p ≤ 0.001). Overall, drivers with NCI (defined as z ≤ 1.00) were more likely than those without NCI to crash (p = 0.002). There were no significant between-group (HIV-positive versus HIV-negative) differences with regard to self-reported on-road driving events. Professional drivers with NCI, as measured on a driving simulator, are at increased risk of making driving errors under high-risk conditions compared to their neurocognitively normal counterparts. These data should inform driver health management with regard to annual medical screening and surveillance.

RESUMEN: La capacidad de conducción puede verse disminuida entre las personas con VIH con deterioro neurocognitivo asociado (neurocognitive impairment, NCI). Exploramos la relación entre la situación frente al VIH, el NCI y la capacidad de conducción en conductores profesionales de camiones. Cuarenta conductores profesionales masculinos (20 seropositivos, edad media = 39.20 ± 7.05) completaron una batería de pruebas neuropsicológicas, dos tareas de simulador de conducción que evaluaron la capacidad de conducción y un cuestionario de hábitos y antecedentes de conducción. Una mayor proporción de conductores VIH positivos exhibió un desempeño cognitivo general deficiente (p ≤ 0.001). En general, los conductores con NCI (definido como z ≤ 1.00) tenían más probabilidades de chocar que aquellos sin NCI (p = 0.002). No hubo diferencias significativas entre los grupos (VIH positivo frente a VIH negativo) con respecto a los eventos autoinformados de conducción en carretera. Los conductores profesionales con NCI, según lo medido en un simulador de conducción, tienen un mayor riesgo de cometer errores de conducción en condiciones de alto riesgo en comparación con sus homólogos neurocognitivamente normales. Estos datos deberían informar a la gestión de la salud del conductor en lo que respecta a la vigilancia y los exámenes médicos anuales.

Construct Validity Supports Use of a Novel, Tablet-Based Neurocognitive Assessment for Adolescents and Young Adults Affected by Perinatal HIV from Vulnerable Communities in the United States.

Construct validity of novel tablet-based neurocognitive tests (in the NeuroScreen app) measuring processing speed, working memory, and executive functioning in adolescents and young adults (AYA) living with perinatally-acquired HIV (PHIV) and perinatal HIV-exposure without infection (PHEU) was examined. Sixty-two AYA (33 PHIV, 29 PHEU) were recruited from an ongoing longitudinal study (CASAH) in New York City. Medium to large and statistically significant correlations were found between NeuroScreen and gold standard, paper-and-pencil tests of processing speed, working memory, and executive functioning. Results provide partial support for NeuroScreen as an alternative to cumbersome paper-and-pencil tests for assessing neurocognition among HIV-affected AYA.

Effect of enclosure expansion on the activity budgets of eastern black-and-white colobus monkeys, Colobus guereza.

Behavior is one of the most observable and informative indicators of animal welfare. This study used behavioral observation methodologies to evaluate the impact of an enclosure expansion on the activity budgets of a group of three eastern black-and-white colobus monkeys, Colobus guereza, housed at the Adelaide Zoo in South Australia. Instantaneous scan sampling methods were used to record the monkeys' behavior before and after they were given access to new aerial walkways at 2-min intervals between 8:30 a.m. and 4:30 p.m., over a total of 109 h (66 baseline hours, 43 post-expansion hours). Broad state behaviors (e.g., social, moving, resting, interacting, and feeding) were recorded and were used to generate activity budgets. Locomotion, feeding, and social behaviors increased following the addition of the aerial walkways, along with an overall increase in activity, attributed to the larger area and increased complexity of the environment. Results indicate that the addition of aerial walkways was effective for increasing the behavioral repertoire in colobus monkeys, aligning activity budgets more closely with their wild counterparts, and increasing active and affiliative behaviors.

Regulation of systemic tissue injury by coagulation inhibitors in B6.MRL/lpr autoimmune mice.

Impaired fibrinolysis and complement activation in Systemic Lupus Erythematosus contributes to disease amplification including increased risk of thrombosis and tissue Ischemia/Reperfusion (IR) injury. Previous work has demonstrated complement is a key regulator of tissue injury. In these studies inhibitors had varying efficacies in attenuating injury at primary versus systemic sites, such as lung. In this study the role of coagulation factors in tissue injury and complement function was evaluated. Tissue Factor Pathway Inhibitor (TFPI), an extrinsic pathway inhibitor, and Anti-Thrombin III, the downstream common pathway inhibitor, were utilized in this study. TFPI was more effective in attenuated primary intestinal tissue injury. However both attenuated systemic lung injury. However, ATIII treatment resulting in enhanced degradation of C3 split products in lung tissue compared to TFPI. This work delineates the influence of specific early and late coagulation pathway components during initial tissue injury versus later distal systemic tissue injury mechanism.

Empowering Lay-Counsellors with Technology: Masivukeni, a Standardized Multimedia Counselling Support Tool to Deliver ART Counselling.

Lay-counsellors in resource-limited settings convey critical HIV- and ART-information, and face challenges including limited training and variable application of counselling. This study explored lay-counsellors and Department of Health (DoH) perspectives on the utility of a multimedia adherence counselling program. Masivukeni, an mHealth application that provides scaffolding for delivering standardized ART counselling was used in a 3-year randomized control trail at two primary health care clinics in Cape Town, South Africa. In this programmatic and descriptive narrative report, we describe the application; lay-counsellors' response to open-ended questions regarding their experience with using Masivukeni; and perspectives of the City of Cape Town and Western Cape Government DoH, obtained through ongoing engagements and feedback sessions. Counsellors reported Masivukeni empowered them to provide high quality counselling. DoH indicated strong support for a future implementation study assessing feasibility for larger scale roll-out. Masivukeni has potential as a counselling tool in resource-limited settings.

Exploring genotype concordance in epidemiologically linked cases of tuberculosis in New York City.

Comparing genotype results of tuberculosis (TB) isolates from individuals diagnosed with TB can support or refute transmission; however, these conclusions are based upon the criteria used to define a genotype match. We used a genotype-match definition which allowed for variation in IS6110 restriction fragment length polymorphism (RFLP) to support transmission between epidemiologically linked persons. Contacts of individuals with infectious TB (index cases) diagnosed in New York City from 1997 to 2003 who subsequently developed TB (contact cases) from 1997 to 2007 were identified. For each contact case and index case (case-pair), isolate genotypes (spoligotype and RFLP results) were evaluated. Isolates from case-pairs were classified as exact or non-exact genotype match. Genotypes from non-exact match case-pairs were reviewed at the genotyping laboratory to determine if the isolates met the near-genotype-match criteria (exactly matching spoligotype and similar RFLP banding patterns). Of 118 case-pairs identified, isolates from 83 (70%) had exactly matching genotypes and 14 (12%) had nearly matching genotypes (supporting transmission), while the remaining 21 (18%) case-pairs had discordant genotypes (refuting transmission). Using identical genotype-match criteria for isolates from case-pairs epidemiologically linked through contact investigation may lead to underestimation of transmission. TB programmes should consider the value of expanding genotype-match criteria to more accurately assess transmission between such cases.

Laboratory tests to identify patients at risk of early major adverse events: a prospective pilot study.

BACKGROUND/AIMS: To test whether commonly measured laboratory variables can identify surgical patients at risk of major adverse events (death, unplanned intensive care unit (ICU) admission or rapid response team (RRT) activation). METHODS: We conducted a prospective observational study in a surgical ward of a university-affiliated hospital in a cohort of 834 surgical patients admitted for >24 h. We applied a previously validated multivariable model-derived risk assessment to each combined set of common laboratory tests to identify patients at risk. We compared the clinical course of such patients with that of control patients from the same ward who had blood tests but were identified as low risk. RESULTS: We studied 7955 batches and 73,428 individual tests in 834 patients (males 55%; average age 65.8 ± 17.6 years). Among these patients, 66 (7.9%) were identified as 'high risk'. High-risk patients were older (75.9 vs 61.8 years of age; P < 0.0001), had much greater early (48 h) mortality (6/66 (9%) vs 4/768 (0.5%); P < 0.0001) and greater overall hospital mortality (11/66 (16.7%) vs 9/768 (1.2%); P < 0.0001). They also had more early (8/66 (12.1%) vs 14/768 (1.8%); P = 0.0001) and overall in-hospital unplanned ICU admissions (12/66 (18.2%) vs 18/768 (2.3%); P < 0.0001) and more early (26/66 (39.3%) vs 50/768 (6.5%); P < 0.0001) and overall in-hospital RRT calls (26/66 (39.4%) vs 55/768 (7.2%); P < 0.0001). CONCLUSIONS: Commonly performed laboratory tests identify surgical ward patients at risk of early major adverse events. Further studies are needed to assess whether such identification system can be used to trigger interventions that help improve patient outcomes.

Morphological and molecular characterization of Paractinolaimus sahandi n. sp. (Nematoda: Actinolaimidae) from the Sahand Mountains in Iran.

Paractinolaimus sahandi n. sp., found in wet soil samples collected from the rhizosphere of grasses of Sahand Mountains, Iran, is described. This new species is characterized by its long body (3.5-4.7 mm), high a value (74.5-88.5), anterior location of posterior subventral nuclei, occupying 62.5-68.0% of glandularium distance, the presence of 1-4 pre- and 1-3 post-vulval papillae and numerous tiny, not innervated papillae in front and behind the vulva in the outer layer of cuticle; common functional males in the population, with 62.5-81.3 µm long spicules and 15-17 ventromedian supplements. The new species, which is the only one in the genus showing the advulval cuticular tiny papillae and is unusually slender, is compared to four species of Paractinolaimus, namely P. macrolaimus, P. longidrilus, P. spanithelus and P. rafiqi. The ribosomal 18S rDNA (1246 bp sequenced) and 28S rDNA D2/D3 region (844 bp sequenced) of P. sahandi n. sp. were sequenced for molecular characterization. Sequences of the 18S and 28S D2/D3 of P. sahandi n. sp. have distinct differences from those of the only sequenced P. macrolaimus, with 6 bp differences in 18S and 38 bp differences and five gaps in 28S. This is the first report of the occurrence of members of Actinolaimidae in Iran.

The epidemiology of Medical Emergency Team calls for orthopedic patients in a teaching hospital: A retrospective cohort study.

BACKGROUND: Patients undergoing orthopedic surgery are at risk of post-operative complications and needing Medical Emergency Team (MET) review. We assessed the frequency of, and associations with MET calls in orthopedic patients, and whether this was associated with increased in-hospital morbidity and mortality. METHODS: Retrospective cohort study of patients admitted over four years to a University teaching hospital using hospital administrative and MET call databases. RESULTS: Amongst 6344 orthopedic patients, 55.8% were female, the median (IQR) age and Charlson comorbidity index were 66 years (47-79) and 3 (1-5), respectively. Overall, 54.5% of admissions were emergency admissions, 1130 (17.8%) were non-operative, and 605 (9.5%) patients received a MET call. The strongest independent associations with receiving a MET call was the operative procedure, especially hip and knee arthroplasty. Common MET triggers were hypotension (37.5%), tachycardia (25.0%) and tachypnoea (9.1%). Patients receiving a MET call were at increased risk of anemia, delirium, pressure injury, renal failure and wound infection. The mortality of patients who received a MET call was 9.8% compared with 0.8% for those who did not. After adjusting for pre-defined co-variates, requirement for a MET call was associated with an adjusted odd-ratio of 9.57 (95%CI 3.1-29.7) for risk of in-hospital death. CONCLUSIONS: Approximately 10% of orthopedic patients received a MET call, which was most strongly associated with major hip and knee arthroplasty. Such patients are at increased risk of morbidity and in-hospital mortality. Further strategies are needed to more pro-actively manage at-risk orthopedic patients.

Indirect imaging of cardiac-specific transgene expression using a bidirectional two-step transcriptional amplification strategy.

Transcriptional targeting for cardiac gene therapy is limited by the relatively weak activity of most cardiac-specific promoters. We have developed a bidirectional plasmid vector, which uses a two-step transcriptional amplification (TSTA) strategy to enhance the expression of two optical reporter genes, firefly luciferase (fluc) and Renilla luciferase (hrluc), driven by the cardiac troponin T (cTnT) promoter. The vector was characterized in vitro and in living mice using luminometry and bioluminescence imaging to assess its ability to mediate strong, correlated reporter gene expression in a cardiac cell line and the myocardium, while minimizing expression in non-cardiac cell lines and the liver. In vitro, the TSTA system significantly enhanced cTnT-mediated reporter gene expression with moderate preservation of cardiac specificity. After intramyocardial and hydrodynamic tail vein delivery of an hrluc-enhanced variant of the vector, long-term fluc expression was observed in the heart, but not in the liver. In both the cardiac cell line and the myocardium, fluc expression correlated well with hrluc expression. These results show the vector's ability to effectively amplify and couple transgene expression in a cardiac-specific manner. Further replacement of either reporter gene with a therapeutic gene should allow non-invasive imaging of targeted gene therapy in living subjects.

Angiogenic effects despite limited cell survival of bone marrow-derived mesenchymal stem cells under ischemia.

Bone marrow-derived mesenchymal stem cells (MSCs) are multipotent and secrete angiogenic factors, which could help patients with occlusive arterial diseases. We hypothesize that MSCs, in comparison to fibroblasts, survive better under hypoxic conditions in vitro and in vivo. MSCs and fibroblasts from L2G mice expressing firefly luciferase and GFP were cultured in normoxic and hypoxic conditions for 24 hours. In vitro cell viability was tested by detecting apoptosis and necrosis. MSCs released higher amounts of VEGF (281.1 +/- 62.6 pg/ml) under hypoxic conditions compared to normoxia (154.9 +/- 52.3 pg/ml, p = NS), but were less tolerant to hypoxia (45 +/- 7.9%) than fibroblasts (28.1 +/- 3.6%, p = NS). A hindlimb ischemia model was created by ligating the femoral artery of 18 FVB mice. After one week, 1 x 106 cells (MSCs, fibroblasts or saline) were injected into the limb muscles of each animal (n = 6 per group). Bioluminescence measurement to assess the viability of luciferase positive cells showed significant proliferation of MSCs on day four compared to fibroblasts (p = 0.001). Three weeks after cell delivery, the capillary to muscle fiber ratio of ischemic areas was analyzed. In the MSC group, vessel density was significantly higher than in the fibroblast or control group (0.5 +/- 0.08 and 0.3 +/- 0.03). Under hypoxia, MSCs produced more VEGF compared to normal conditions and MSC transplantation into murine ischemic limbs led to an increase in vessel density, although MSC survival was limited. This study suggests that MSC transplantation may be an effective and clinically relevant tool in the therapy of occlusive arterial diseases.

First Record of Trichodorus primitivus and Morphological and Molecular Identification of Longidorus elongatus from Canada.

During July 2008, sandy loam soil samples were collected near the rhizosphere of Kentucky bluegrass (Poa pratensis L.) and tall fescue (Festuca arundinacea Schreb.) at a depth of 15 to 20 cm from Caledonia Park, Toronto, Canada. Samples were suspended in water and nematodes were collected on sieves with 250- and 74-µm openings. Among the nematodes recovered were one species of Longidorus Micoletzky, 1922 (4) and one species of Trichodorus Cobb, 1913. The Trichodorus species (2), was identified as T. primitivus (de Man, 1880) Micoletzky, 1922, in which females have rod-like sclerotized pieces parallel to the vagina lumen, each with dimensions of 3.1 × 1.2 µm and at a distance of 2 to 3 µm from each other; and males have spicules with a wide nonoffset capitulum and very narrow blade, three ventromedian cervical papillae (CP), and three precloacal supplements with the anterior one at the level of the capitulum of retracted spicules. Males showed unusual variation in the position of CP2 (i.e., posterior to the onchiostyle region, except for one specimen with CP2 located within the posterior onchiostyle region, which is typical for the species). The morphometric data for nine males are: L, 665 to 805 µm; a, 23.0 to 27.5; b, 3.7 to 5.2; c, 46 to 56; onchiostyle, 47 to 52 µm; and spicules, 32.5 to 40.5 µm. Measurements for 13 females are: L, 630 to 775 µm; a, 20.5 to 24.8; b, 3.5 to 5.5; c, 75.5 to 158.5; and V, 54 to 61%. To our knowledge, this is the first report of T. primitivus in Canada. According to Chen et al. (1), the Longidorus species was identified as L. elongatus (de Man, 1876) Micoletzky, 1922 (3). The morphometric data for females (n = 13) are: L, 5.1 to 6.0 mm; a, 78.5 to 106.5; b, 11.5 to 13.5; c, 86.0 to 120.5; V, 45.5 to 53.0%; odontostyle, 79 to 91 µm; odontophore, 57.5 to 66.5 µm; and tail length, 44.5 to 59.0 µm. Males were not found. Four juvenile stages were identified. J1 (n = 2) with a body length of 1.1, 1.2 mm and replacement/functional odontostyle 59, 59/53.5, 54.5 µm, J2 (n = 2) with L: 1.7, 2.0 mm and replacement/functional odontostyle 62.5, 68.0/58.7 µm, 59.0, J3 (n = 2): L: 2.8, 3.0 mm and replacement/functional odontostyle 76.5, 77/66.5, 67.0 µm and J4 (n = 2) with L: 3.6, 3.8 mm and replacement/functional odontostyle 87.0, 90.5/75.0, 77.5 µm. Due to large morphometric overlap in Longidorus species identification, 2,472 bp of the near full-length 18S and the internal transcribed spacer 1 region of rDNA (Accession No. GU199044) were sequenced. The Blastn search of the partial 18S revealed 100% identity with a population of L. elongatus from Scotland (GenBank No. AY687992, 1,707 bp compared), 99% identity (3 bp difference, 1,707 bp compared) with a population of L. elongatus from Iran (EU503141) and 99% identity (4 bp difference, 1,707 bp compared) with a population of L. elongatus (AF036594, sample location unknown). A Blastn search of the 18S and ITS region revealed only 1 to 3 bp differences with two populations of L. elongatus from Switzerland (AJ549986 and AJ549987) and a population of L. elongatus (AF511417) from Scotland. These molecular data further confirmed the identity of the population from Canada to be L. elongatus. References: (1) Q. Chen et al. Fundam. Appl. Nematol. 20:15, 1997. (2) W. Decraemer. Kluwer Academic Publishers, Dordrecht, the Netherlands, 1995. (3) J. G. de Man. Tijdschr. Ned. Dierk. Ver. 2:78, 1876. (4) H. Micoletzky. Archiv. Naturgesch. 87:1, 1922.

Diabetes and higher HbA1c levels are independently associated with adverse renal outcomes in inpatients following multiple hospital admissions.

OBJECTIVE: To assess the association between glycaemic status prior to the first hospital presentation with developing adverse renal outcomes overtime in patients with multiple hospital re-admissions. DESIGN: A prospective observational cohort study. PARTICIPANTS: All inpatients aged ≥54 years admitted between 2013 and 16 to a tertiary hospital. MAIN OUTCOMES: We prospectively measured HbA1c levels in all inpatients aged ≥54 years admitted between 2013 and 16. Diabetes was defined as prior documented diagnosis of diabetes and/or HbA1c ≥6.5% (47·5 mmol/L). Included patients had ≥ two admissions (at least 90 days apart), baseline estimated glomerular filtration rate (eGFR) >30 ml/min/1·73m2 and no history of renal replacement therapy. We assessed several renal outcomes: (a) 50% decline in eGFR; (b) rapid decline in renal function (eGFR decline >5 mL/min/1·73m2/year) and (c) final eGFR<30 ml/min/1·73m2. RESULTS: Of 4126 inpatients with a median follow-up of 465 days (254, 740), 26% had diabetes. The presence of diabetes was associated with higher odds of (a) 50% decline in eGFR (OR = 1·42;95% CI:1·18-1·70;p < 0·001); (b) rapid decline in renal function (OR = 1·40;95%CI:1·20-1·63;p < 0·001), and (c) reaching eGFR<30 ml/min/1.73m2 (OR = 1·25;95%CI:1·03-1·53;p < 0·05). Every 1% (11 mmol/L) increase in baseline HbA1c was associated with significantly greater odds of (a) >50% decline in eGFR (OR = 1·07;95% CI:1·01-1·4;p < 0·05) and (b) rapid decline in renal function (OR = 1·11;95% CI:1·05-1·18;p < 0·001). CONCLUSIONS: In patients with ≥two admissions, the presence of diabetes and higher HbA1c levels were strongly and independently associated with adverse renal outcomes at follow up. Such patients are at high risk of relatively rapid deterioration in renal function and a logical target for structured preventive interventions.

Cryopreservation, culture, and transplantation of human fetal mesencephalic tissue into monkeys.

Studies in animals suggest that fetal neural grafts might restore lost neurological function in Parkinson's disease. In monkeys, such grafts survive for many months and reverse signs of parkinsonism, without attendant graft rejection. The successful and reliable application of a similar transplantation procedure to human patients, however, will require neural tissue obtained from human fetal cadavers, with demonstrated cellular identity, viability, and biological safety. In this report, human fetal neural tissue was successfully grafted into the brains of monkeys. Neural tissue was collected from human fetal cadavers after 9 to 12 weeks of gestation and cryopreserved in liquid nitrogen. Viability after up to 2 months of storage was demonstrated by cell culture and by transplantation into monkeys. Cryopreservation and storage of human fetal neural tissue would allow formation of a tissue bank. The stored cells could then be specifically tested to assure their cellular identity, viability, and bacteriological and virological safety before clinical use. The capacity to collect and maintain viable human fetal neural tissue would also facilitate research efforts to understand the development and function of the human brain and provide opportunities to study neurological diseases.

Trends in invasive disease due to Candida species following heart and lung transplantation.

Although invasive candidiasis (IC) causes significant morbidity and mortality in patients who undergo heart, lung, or heart-lung transplantation, a systematic study in a large cohort of thoracic organ transplant recipients has not been reported to date. Clinical and microbiological data were reviewed for 1305 patients who underwent thoracic organ transplantation at Stanford University Medical Center between 1980 and 2004. We identified and analyzed 76 episodes of IC in 68 patients (overall incidence 5.2% per patient).The incidence of IC was higher in lung (LTx) and heart-lung transplant (HLTx) recipients as compared with heart transplant (HTx) recipients (risk ratio [RR] 1.7, 95% confidence interval [CI] 1.1-2.7).The incidence of IC decreased over time in all thoracic organ transplant recipients, decreasing from 6.1% in the 1980-1986 time period to 2.1% in the 2001-2004 era in the HTx recipients, and from 20% in the 1980-1986 period to 1.8% in the 2001-2004 period in the LTx and HLTx recipients.The most common site of infection differed between the HTx and LTx cohorts, with bloodstream or disseminated disease in the former and tracheobronchitis in the latter. IC in the first year after transplant was significantly associated with death in both HTx (RR 2.9, 95% CI 1.8-4.6, P=0.001) and LTx and HLTx patients (RR 3.0, 95% CI 1.9-4.6, P<0.001). The attributable mortality from IC decreased during the 25-year period of observation, from 36% to 20% in the HTx recipients and from 39% to 15% in the LTx and HLTx recipients. There were a significant number of cases caused by non-albicans Candida species in all patients, with a trend toward higher mortality in the HTx group. In conclusion, the incidence and attributable mortality of IC in thoracic organ transplant recipients has significantly declined over the past 25 years.The use of newer antifungal agents for prophylaxis and treatment, the decrease in the incidence of cytomegalovirus disease, and the use of more selective immunosuppression, among other factors, may have been responsible for this change.

Longidorus ferrisi n. sp. from California Citrus.

In October 1999, the authors received fixed specimens of a species of Longidorus from Howard Ferris found about the roots of a citrus tree in Oakville, Napa County, CA. After determining it to be new a species, we requested additional specimens. The samples contained roughly equal numbers of males and females. Longidorus ferrisi n. sp. is most similar to L. elongatus, but can be distinguished by a greater c-ratio (111-187 vs 73-141), a lesser c´ (0.7-1.1 vs 1.0-1.3), a more offset head, a more posterior guide ring (35-40 vs 30-33 µm), the presence of sperm in the uterus in mature females, and the approximate 1:1 ratio of females to males. Other similar species include L. artemisiae, L. crassus, L. glycines, and L. milanis. Longidorus ferrisi n. sp. differs from L. artemisiae by a lesser a-ratio (74-102 vs 109-155), a lesser c´ value (0.7-1.1 vs 1.0-1.6), a more posterior guide ring (35-40 vs 27-34 µm), a longer odontostyle (91-108 vs 84-98 µm), a wider lip region (16-19 vs 14-17 µm), wider mid-body (53-69 vs 41-52 µm), and longer spicules (57-65 vs 39-49 µm). The new species differs substantially from L. crassus by its lip shape and the presence of males, and differs from L. glycines by a shorter body (4.33-5.97 vs 6.14-8.31 mm), a lesser c´ value (0.7-1.1 vs 0.9-1.4), a narrower lip region (16-19 vs 20-23 µm), wider mid-body (53-69 vs 39-57 µm), longer spicules (53-69 vs 45-53 µm), and fewer supplements (7-11 vs 11-17). Longidorus ferrisi n. sp. differs from L. milanis by a longer body (4.33-5.97vs 3.00-4.90 mm), a greater c value (111-187 vs 86-130), a wider mid-body (53-69 vs 43-56 µm), a different head shape, and longer spicules (53-69 vs 41-54 µm). The nuclear 18S ribosomal DNA sequence of this species revealed that this species is unique with respect to all sequenced Longidorus species.