Amdoparvovirus-associated disease in red pandas (Ailurus fulgens).

The roster of amdoparvoviruses (APVs) in small carnivores is growing rapidly, but in most cases, the consequences of infection are poorly understood. Red panda amdoparvovirus (RPAV) is highly prevalent in zoo-housed red pandas and has been detected in both healthy and sick animals. Clarifying the clinical impact of RPAV in this endangered species is critical, and zoological collections offer a unique opportunity to examine viral disease association in carefully managed populations. We evaluated the potential impact of RPAV in captive red pandas with a combination of prospective and retrospective analyses. First, we collected feces from 2 healthy animals from one collection over a 6-year period and detected virus in 72/75 total samples, suggesting that RPAV can be a long-term subclinical infection. We next investigated the infections using a retrospective study of infection status and tissue distribution in a cohort of necropsied animals. We performed polymerase chain reaction and in situ hybridization on 43 necropsy cases from 4 zoo collections (3 from the United States, 1 from Europe, 1997-2022). RPAV was present in these populations for at least 2 decades before its discovery and is detectable in common and significant lesions of zoo-housed red pandas, including myocarditis (3/3 cases), nephritis (9/10), and interstitial pneumonia (2/4). RPAV is also detectable in sporadic lesions, including multisystemic pyogranulomatous inflammation, oral/pharyngeal mucosal inflammation, and dermatitis. The colocalization of virus with lesions supports a role in causation, suggesting that despite the apparently persistent and subclinical carriage of most infections, RPAV may have a significant impact in zoo collections.

The utility of the Sydney Melancholia Prototype Index (SMPI) for predicting response to electroconvulsive therapy in depression: A CARE Network study.

An enhanced understanding of clinical predictors of positive ECT outcome could assist with the decision to prescribe ECT for select patients. Reliable predictors of ECT response such as psychotic symptoms and age have been identified, however, studies of melancholia and ECT response have been inconsistent. The Sydney Melancholia Prototype Index (SMPI) is a clinical measure designed to differentiate melancholic and non-melancholic depression. This study aimed to investigate whether melancholic depression (as measured by the clinician rated version of the SMPI) predicted a better response to ECT than non-melancholic depression. The study included data collated from four participating sites in the Clinical Alliance for ECT and Related treatments (CARE) network. The primary outcome was response (>50% improvement) on the Montgomery Asberg Depression Rating Scale (MADRS) and the secondary outcome was raw change in MADRS score. Of the 329 depressed patients included in the study, 81% had melancholic features and 76% met criteria for clinical response. SMPI defined melancholia was associated with older age, higher pre-treatment mood scores and presence of psychosis. Melancholia as defined by the SMPI, however, did not significantly predict either clinical response or overall mood improvement with ECT in multivariate analyses. Instead, older age, greater pre-treatment depression severity and the use of bifrontal compared to right unilateral ultrabrief ECT were significant predictors of mood improvement. Path analysis showed that higher pre-treatment mood score and older age were independently associated with mood improvement with ECT.

The utility of the brief ECT cognitive screen (BECS) for early prediction of cognitive adverse effects from ECT: A CARE network study.

Although highly effective, electroconvulsive therapy (ECT) often produces cognitive side effects which can be a barrier for patients. Monitoring cognitive side effects during the acute course is therefore recommended to identify patients at increased risk for adverse outcomes. The Brief ECT Cognitive Screen (BECS) is a brief instrument designed to measure emerging cognitive side effects from ECT. The aim of this study was to examine the clinical utility of the BECS for predicting adverse cognitive outcomes in real world clinic settings. The study included data collated from four participating sites in the Clinical Alliance for ECT and Related treatments (CARE) network. The BECS was administered at pre ECT and post 3 or 4 ECT. The primary outcome was a ≥4 point decrease on the Montreal Cognitive Assessment (MoCA) from pretreatment to post ECT. Logistic multiple regression analyses examined the BECS and other relevant clinical and demographic and treatment factors as predictors. The final analysis included 623 patients with diverse indications for ECT including 53.6% with major depression and 33.7% with schizophrenia or schizoaffective disorder. A higher total score on the BECS significantly predicted decline in Total Scores on the MoCA [B = 0.25 (0.08), p = 0.003], though not decline in MoCA Delayed Recall scores (p > 0.1). Other significant predictors included higher pretreatment MoCA Total Scores and female gender for verbal anterograde memory decline. This study confirmed that the BECS has clinical utility for identifying patients with both reduced and increased risk for adverse cognitive outcomes from ECT.

Timing of geological events in the lunar highlands recorded in shocked zircon-bearing clasts from Apollo 16.

Apollo 16 soil-like regolith breccia 65745,7 contains two zircon-bearing clasts. One of these clasts is a thermally annealed silica-rich rock, which mineralogically has affinities with the High Alkali Suite (Clast 1), and yields zircon dates ranging from 4.08 to 3.38 Ga. The other clast is a KREEP-rich impact melt breccia (Clast 2) and yields zircon dates ranging from 3.97 to 3.91 Ga. The crystalline cores of both grains, which yield dates of ca 3.9 Ga, have undergone shock pressure modification at less than 20 GPa. We interpret that the U-Pb chronometer in these zircon grains has been partially reset by the Imbrium basin-forming event when the clasts were incorporated into the Cayley Plains ejecta blanket deposit. The zircon grains in Clast 1 have been partially decomposed, resulting in a breakdown polymineralic texture, with elevated U, Pb and Th abundances compared with those in the crystalline zircon. These decomposed areas exhibit younger dates around 3.4 Ga, suggesting a secondary high-pressure, high-temperature event, probably caused by an impact in the local Apollo 16 highlands area.

Non-monetary valuation using Multi-Criteria Decision Analysis: Sensitivity of additive aggregation methods to scaling and compensation assumptions.

Analytical methods for Multi-Criteria Decision Analysis (MCDA) support the non-monetary valuation of ecosystem services for environmental decision making. Many published case studies transform ecosystem service outcomes into a common metric and aggregate the outcomes to set land use planning and environmental management priorities. Analysts and their stakeholder constituents should be cautioned that results may be sensitive to the methods that are chosen to perform the analysis. In this article, we investigate four common additive aggregation methods: global and local multi-attribute scaling, the analytic hierarchy process, and compromise programming. Using a hypothetical example, we explain scaling and compensation assumptions that distinguish the methods. We perform a case study application of the four methods to re-analyze a data set that was recently published in Ecosystem Services and demonstrate how results are sensitive to the methods.

Dutch Translation and Validation of the Headache-Specific Locus of Control Scale (HSLC-DV).

Background and Objective: The assessment of locus of control forms an important part of headache treatment, and there is need to adapting them to the Dutch population. Methods: Forward-backward translation was used to obtain the Headache-Specific Locus of Control Scale-Dutch Version (HSLC-DV). The response of 87 participants with migraine, tension-type headache, and cervicogenic headache, aged between 18 and 55 years (75% female), is used. Test-retest reliability was measured by intraclass correlations. Construct validity was assessed by correlations with corresponding domains of the Pain Coping and Cognition List (PCCL) and by confirmation of known groups hypotheses. Structural validity was evaluated by factor analysis (principal axis factoring). Results: The intraclass correlations for the External, Internal, and Chance domains were 0.79, 0.89, and 0.73, respectively. Internal consistencies for domains exceeded 0.73 and were similar to those observed in the original study. Convergent correlations were as expected and three of the seven known groups hypotheses were confirmed. Structural validity was supported by results of the factor analysis that matched the proposed structure of the original instrument. Conclusions: The HSLC-DV is a valid and reliable questionnaire for measuring the locus of control.

Clinical pilot study of transcranial direct current stimulation combined with Cognitive Emotional Training for medication resistant depression.

BACKGROUND: While the clinical results from transcranial direct current stimulation (tDCS) for the treatment of depression have been promising, antidepressant effects in patients with medication resistance have been suboptimal. There is therefore a need to further optimise tDCS for medication resistant patients. In this clinical pilot study we examined the feasibility, safety, and clinical efficacy of combining tDCS with a psychological intervention which targets dysfunctional circuitry related to emotion regulation in depression, Cognitive Emotional Training (CET). METHODS: tDCS was administered during CET three times a week for a total of 18 sessions over 6 weeks. Mood, cognition and emotion processing outcomes were examined at baseline and after 3 and 6 weeks of treatment. RESULTS: Twenty patients with medication resistant depression participated, of whom 17 were study completers. tDCS combined with CET was found to be feasible, safe, and associated with significant antidepressant efficacy at 6 weeks, with 41% of study completers showing treatment response (≥ 50% improvement in depression score). There were no significant cognitive enhancing effects with the exception of improved emotion recognition. Responders demonstrated superior recognition for the emotions fear and surprise at pre-treatment compared to non-responders, suggesting that better pre-treatment emotion recognition may be associated with antidepressant efficacy. LIMITATIONS: This was an open label study. CONCLUSIONS: tDCS combined with CET has potential as a novel method for optimising the antidepressant efficacy of tDCS in medication resistant patients. Future controlled studies are required to determine whether tDCS combined with CET has greater antidepressant efficacy compared to either intervention alone.

Non-monetary valuation using Multi-Criteria Decision Analysis: Using a strength-of-evidence approach to inform choices among alternatives.

This article demonstrates an approach to Multi-Criteria Decision Analysis that compares non-monetary ecosystem service (ES) outcomes for environmental decision making. ES outcomes are often inadequately defined and characterized by imprecision and uncertainty. Outranking methods enrich our understanding of the imperfect knowledge of ES outcomes by allowing decision makers to closely examine and apply preference measures to relationships among the outcomes. We explain the methodological assumptions related to the Preference Ranking Organization METHod for Enrichment Evaluation (PROMETHEE) method, and apply it to a wetland restoration planning study in Rhode Island, USA. In the study, we partnered with a watershed management organization to evaluate four wetland restoration alternatives for their abilities to supply five ES: flood water regulation, scenic landscapes, learning opportunities, recreation, and birds. Twenty-two benefit indicators were identified for the ES as well as one indicator for social equity and one indicator for reliability of ES provision. We developed preference functions to characterize the strength of evidence across estimated indicator values between pairs of alternatives. We ranked the alternatives based on these preferences and weights on ES relevant to different planning contexts. We discuss successes and challenges of implementing PROMETHEE, including feedback from our partners who utilized the methods.

Diagnostic accuracy of upper cervical spine instability tests: a systematic review.

BACKGROUND: Patients with neck pain, headache, torticollis, or neurological signs should be screened carefully for upper cervical spine instability, as these conditions are "red flags" for applying physical therapy interventions. However, little is known about the diagnostic accuracy of upper cervical spine instability tests. PURPOSE: The purpose of this study was to evaluate the diagnostic accuracy of upper cervical spine instability screening tests in patients or people who are healthy. DATA SOURCES: PubMed, CINAHL, EMBASE, and RECAL Legacy databases were searched from their inception through October 2012. STUDY SELECTION: Studies were included that assessed the diagnostic accuracy of upper cervical instability screening tests in patients or people who are healthy and in which sensitivity and specificity were reported or could be calculated using a 2 × 2 table. DATA EXTRACTION AND QUALITY ASSESSMENT: Two reviewers independently performed data extraction and the methodological quality assessment using the QUADAS-2. DATA SYNTHESIS: Depending on heterogeneity, statistical pooling was performed. All diagnostic parameters (sensitivity, specificity, predictive values, and likelihood ratios) were recalculated, if possible. RESULTS: Five studies were included in this systematic review. Statistical pooling was not possible due to clinical and statistical heterogeneity. Specificity of 7 tests was sufficient, but sensitivity varied. Predictive values were variable. Likelihood ratios also were variable, and, in most cases, the confidence intervals were large. LIMITATIONS: The included studies suffered from several biases. None of the studies evaluated upper cervical spine instability tests in patients receiving primary care. CONCLUSIONS: The membranes tests had the best diagnostic accuracy, but their applicability as a test for diagnosing upper cervical spine instability in primary care has yet to be confirmed.

Diagnostic accuracy of premanipulative vertebrobasilar insufficiency tests: a systematic review.

STUDY DESIGN: A systematic review of diagnostic accuracy studies. OBJECTIVE: To evaluate the diagnostic accuracy of the premanipulative vertebrobasilar insufficiency (VBI) tests. SUMMARY OF BACKGROUND DATA: The aim of premanipulative vertebrobasilar testing is to evaluate the adequacy of blood supply to the brain, by compressing the vertebral artery and examining for the onset of signs and symptoms of cerebrovascular ischemia. Although clinicians consider pre-manipulative testing important before applying spinal manipulations, the diagnostic accuracy has not been systematically reviewed. METHODS: A search was made in PUBMED, CINAHL and EMBASE databases from their date of inception until 2nd May 2012. Studies were included if they compared a VBI test with a reference test, and sensitivity and specificity were reported or could be calculated. The methodological quality of the studies was evaluated using QUADAS. Agreement between reviewers was calculated and expressed as a percentage and quantified by kappa statistics. RESULTS: Of the 1677 potential citations only 4 studies were included, all of questionable quality. Sensitivity was low and ranged from 0 to 57%, specificity from 67 to 100%, positive predictive value from 0% to 100%, and negative predictive value from 26 to 96%. The positive likelihood ratio ranged from 0.22 to 83.25 and the negative likelihood ratio from 0.44 to 1.40. CONCLUSION: Based on this systematic review of only 4 studies it was not possible to draw firm conclusions about the diagnostic accuracy of premanipulative tests. However, data on diagnostic accuracy indicate that the premanipulative tests do not seem valid in the premanipulative screening procedure. A surplus value for premanipulative tests seems unlikely.

GABAergic and glutamatergic identities of developing midbrain Pitx2 neurons.

Pitx2, a paired-like homeodomain transcription factor, is expressed in post-mitotic neurons within highly restricted domains of the embryonic mouse brain. Previous reports identified critical roles for PITX2 in histogenesis of the hypothalamus and midbrain, but the cellular identities of PITX2-positive neurons in these regions were not fully explored. This study characterizes Pitx2 expression with respect to midbrain transcription factor and neurotransmitter phenotypes in mid-to-late mouse gestation. In the dorsal midbrain, we identified Pitx2-positive neurons in the stratum griseum intermedium (SGI) as GABAergic and observed a requirement for PITX2 in GABAergic differentiation. We also identified two Pitx2-positive neuronal populations in the ventral midbrain, the red nucleus, and a ventromedial population, both of which contain glutamatergic precursors. Our data suggest that PITX2 is present in regionally restricted subpopulations of midbrain neurons and may have unique functions that promote GABAergic and glutamatergic differentiation.

Bone properties surrounding hydroxyapatite-coated custom osseous integrated dental implants.

Calcium phosphate (hydroxyapatite or HA) coatings have been applied to Custom Osseous Integrated Implants (COIIs) to improve the quality of the bone-implant integration, yet little is known concerning the biomechanical properties of bone surrounding the HA-coated implants in humans over the long term. The purpose of this study was to characterize the mechanical and histomorphometric properties of the bone along the implant interface. Specimens were prepared from three similar mandibular implants that were functional in three female patients for about 11 years. Histomorphometric analyses showed bone-implant contact averaging 75% for all specimens. Area coverage of residual HA-coating ranged from 52 to 70%. When compared with previous studies, these results show a relatively high percentage of residual HA after a decade in vivo. Nanoindentation showed similar average values of hardness and modulus (p = 0.53 and p = 0.56, respectively) comparing bone adjacent to residual HA-coating and regions where the coating was absent. The elastic modulus was significantly lower for bone near the bone-implant interface (<200 µm) as compared with bone distant (>1000 µm) from the interface (p = 0.05), thereby reflecting different properties of the bone near these interfaces. Backscattered electron imaging showed darker gray levels which indicated decreased mineral content in bone adjacent to the implant, consistent with the nanoindentation results.

Chromodomain proteins in development: lessons from CHARGE syndrome.

In humans, heterozygous mutations in the adenosine triphosphate-dependent chromatin remodeling gene CHD7 cause CHARGE syndrome, a common cause of deaf-blindness, balance disorders, congenital heart malformations, and olfactory dysfunction with an estimated incidence of approximately 1 in 10,000 newborns. The clinical features of CHARGE in humans and mice are highly variable and incompletely penetrant, and most mutations appear to result in haploinsufficiency of functional CHD7 protein. Mice with heterozygous loss of function mutations in Chd7 are a good model for CHARGE syndrome, and analyses of mouse mutant phenotypes have begun to clarify a role for CHD7 during development and into adulthood. Chd7 heterozygous mutant mice have postnatal delayed growth, inner ear malformations, anosmia/hyposmia, and craniofacial defects, and Chd7 homozygous mutants are embryonic lethal. A central question in developmental biology is how chromodomain proteins like CHD7 regulate important developmental processes, and whether they directly activate or repress downstream gene transcription or act more globally to alter chromatin structure and/or function. CHD7 is expressed in a wide variety of tissues during development, suggesting that it has tissue-specific and developmental stage-specific roles. Here, we review recent and ongoing analyses of CHD7 function in mouse models and cell-based systems. These studies explore tissue-specific effects of CHD7 deficiency, known CHD7 interacting proteins, and downstream target sites for CHD7 binding. CHD7 is emerging as a critical regulator of important developmental processes in organs affected by human CHARGE syndrome.

Defects in neural stem cell proliferation and olfaction in Chd7 deficient mice indicate a mechanism for hyposmia in human CHARGE syndrome.

Mutations in CHD7, a chromodomain gene, are present in a majority of individuals with CHARGE syndrome, a multiple anomaly disorder characterized by ocular Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital hypoplasia and Ear anomalies. The clinical features of CHARGE syndrome are highly variable and incompletely penetrant. Olfactory dysfunction is a common feature in CHARGE syndrome and has been potentially linked to primary olfactory bulb defects, but no data confirming this mechanistic link have been reported. On the basis of these observations, we hypothesized that loss of Chd7 disrupts mammalian olfactory tissue development and function. We found severe defects in olfaction in individuals with CHD7 mutations and CHARGE, and loss of odor evoked electro-olfactogram responses in Chd7 deficient mice, suggesting reduced olfaction is due to a dysfunctional olfactory epithelium. Chd7 expression was high in basal olfactory epithelial neural stem cells and down-regulated in mature olfactory sensory neurons. We observed smaller olfactory bulbs, reduced olfactory sensory neurons, and disorganized epithelial ultrastructure in Chd7 mutant mice, despite apparently normal functional cilia and sustentacular cells. Significant reductions in the proliferation of neural stem cells and regeneration of olfactory sensory neurons in the mature Chd7(Gt/+) olfactory epithelium indicate critical roles for Chd7 in regulating neurogenesis. These studies provide evidence that mammalian olfactory dysfunction due to Chd7 haploinsufficiency is linked to primary defects in olfactory neural stem cell proliferation and may influence olfactory bulb development.

New hosts for equine herpesvirus 9.

Equine herpesvirus 9 was detected in a polar bear with progressive encephalitis; the source was traced to 2 members of a potential equid reservoir species, Grevy's zebras. The virus was also found in an aborted Persian onager. Thus, the natural host range is extended to 6 species in 3 mammalian orders.

Personality disorders in people with learning disabilities: follow-up of a community survey.

BACKGROUND: A sample of community-based service users with intellectual disability (ID) was re-examined after 5 years to determine the impact of a diagnosis of personality disorder (PD). METHODS: Seventy-five of the original 101 participants were followed up. Of these, 21 people had a PD identified during the original study. RESULTS: Compared with controls, people with a PD were significantly more likely to receive central nervous system (CNS) drugs, have more contact with psychiatric services, show increased offending behaviour, score higher on the Aberrant Behaviour Checklist and score above the threshold on the Psychiatric Assessment Schedule for Adults with Developmental Disability (PAS-ADD). Participants with PD recorded were more likely to have a recorded psychiatric disorder, have contact with specialist teams, and have more hospital admissions. CONCLUSION: People with ID and PD are able to live in the community with specialist support but improved assessment, diagnosis and support services need to be targeted more effectively to them.

Assessment of a contrast medium as an adjunct to endodontic radiography.

AIM: To assess if a contrast medium improved diagnostic yield of endodontic radiographs. METHODOLOGY: Forty-five extracted mandibular premolar teeth were radiographed in bucco-lingual and mesio-distal planes. Access cavities were prepared, pulpal tissue extirpated and Ultravist contrast medium introduced under pressure. Radiographs were retaken and the teeth cleared following perfusion with India ink. Three examiners assessed all the films for: number of roots, number of root canals, curvature of root and/or root canal, presence of lateral canals, presence of a single foramen or apical delta and the presence or absence of canal obstructions. The examiners' interpretations were compared with the anatomy revealed by clearing. RESULTS: Kappa scores were calculated for each of the examiners, for each set of radiographs, to assess the level of intra- and inter-examiner agreement. Only moderate agreement was found throughout (kappa = 0.40-0.61). For multiple root canals a false-positive result was significantly more likely with contrast (P < 0.05). The use of contrast did not significantly improve the sensitivity of diagnosis of lateral canals or a single apical foramen. Contrast significantly increased the risk of falsely perceiving lateral canals (P < 0.002). Overall there was no statistically significant difference in the overall assessment of the anatomy of the root canals using contrast or plain radiographs (P > 0.2). CONCLUSIONS: Plain film radiographs confidently predict the presence of root or canal curvature but apical anatomy was assessed accurately in only 46% of cases. Plain radiographs were insensitive in assessing the number of root canals present, the presence of lateral canals and the occurrence of canal obstructions. The use of Ultravist contrast medium to improve diagnosis of root canal morphology of premolars is not supported.