Vocal and tongue exercise in early to mid-stage Parkinson disease using the Pink1-/- rat.

Vocal and swallowing deficits are common in Parkinson disease (PD). Because these impairments are resistant to dopamine replacement therapies, vocal and lingual exercise are the primary treatment, but not all individuals respond to exercise and neural mechanisms of treatment response are unclear. To explore putative mechanisms, we used the progressive Pink1-/- rat model of early to mid-stage PD and employed vocal and lingual exercises at 6- and 10-months of age in male Pink1-/- and wild type (WT) rats. We hypothesized that vocal and lingual exercise would improve vocal and tongue use dynamics and increase serotonin (5HT) immunoreactivity in related brainstem nuclei. Rats were tested at baseline and after 8 weeks of exercise or sham exercise. At early-stage PD (6 months), vocal exercise resulted in increased call complexity, but did not change intensity, while at mid-stage (10 months), vocal exercise no longer influenced vocalization complexity. Lingual exercise increased tongue force generation and reduced relative optical density of 5HT in the hypoglossal nucleus at both time points. The effects of vocal and lingual exercise at these time points are less robust than in prodromal stages observed in previous work, suggesting that early exercise interventions may yield greater benefit. Future work targeting optimization of exercise at later time points may facilitate clinical translation.

Preferential responses to faces in superior temporal and medial prefrontal cortex in three-year-old children.

Perceiving faces and understanding emotions are key components of human social cognition. Prior research with adults and infants suggests that these social cognitive functions are supported by superior temporal cortex (STC) and medial prefrontal cortex (MPFC). We used functional near-infrared spectroscopy (fNIRS) to characterize functional responses in these cortical regions to faces in early childhood. Three-year-old children (n = 88, M(SD) = 3.15(.16) years) passively viewed faces that varied in emotional content and valence (happy, angry, fearful, neutral) and, for fearful and angry faces, intensity (100%, 40%), while undergoing fNIRS. Bilateral STC and MPFC showed greater oxygenated hemoglobin concentration values to all faces relative to objects. MPFC additionally responded preferentially to happy faces relative to neutral faces. We did not detect preferential responses to angry or fearful faces, or overall differences in response magnitude by emotional valence (100% happy vs. fearful and angry) or intensity (100% vs. 40% fearful and angry). In exploratory analyses, preferential responses to faces in MPFC were not robustly correlated with performance on tasks of early social cognition. These results link and extend adult and infant research on functional responses to faces in STC and MPFC and contribute to the characterization of the neural correlates of early social cognition.

Cat scratch disease: U.S. clinicians' experience and knowledge.

Cat scratch disease (CSD) is a zoonotic infection caused primarily by the bacterium Bartonella henselae. An estimated 12,000 outpatients and 500 inpatients are diagnosed with CSD annually, yet little is known regarding clinician experience with and treatment of CSD in the United States. Questions assessing clinical burden, treatment and prevention of CSD were posed to 3,011 primary care providers (family practitioners, internists, paediatricians and nurse practitioners) during 2014-2015 as part of the annual nationwide DocStyles survey. Among the clinicians surveyed, 37.2% indicated that they had diagnosed at least one patient with CSD in the prior year. Clinicians in the Pacific and Southern regions were more likely to have diagnosed CSD, as were clinicians who saw paediatric patients, regardless of specialty. When presented with a question regarding treatment of uncomplicated CSD, only 12.5% of clinicians chose the recommended treatment option of analgesics and monitoring, while 71.4% selected antibiotics and 13.4% selected lymph node aspiration. In a scenario concerning CSD prevention in immunosuppressed patients, 80.6% of clinicians chose some form of precaution, but less than one-third chose the recommended option of counseling patients to treat their cats for fleas and avoid rough play with their cats. Results from this study indicate that a substantial proportion of U.S. clinicians have diagnosed CSD within the past year. Although published guidelines exist for treatment and prevention of CSD, these findings suggest that knowledge gaps remain. Therefore, targeted educational efforts about CSD may benefit primary care providers.

Early deprivation, atypical brain development, and internalizing symptoms in late childhood.

Children exposed to extreme early-life neglect such as in institutional rearing are at heightened risk for developing depression and anxiety disorders, and internalizing problems more broadly. These outcomes are believed to be due to alterations in the development of neural circuitry that supports emotion regulation. The specific neurodevelopmental changes that contribute to these difficulties are largely unknown. This study examined whether microstructural alterations in white matter pathways predicted long-term risk for internalizing problems in institutionally reared children. Data from 69 children were drawn from the Bucharest Early Intervention Project, a randomized clinical trial of foster care for institutionally reared children. White matter was assessed using diffusion tensor imaging (DTI) when children were between 8 and 10years of age. Internalizing symptoms were assessed at the time of the MRI scan, and once children reached 12-14years of age. Results indicated that neglect-associated alterations in the external capsule and corpus callosum partially explained links between institutional rearing status and internalizing symptoms in middle childhood and early adolescence. Findings shed light on neural mechanisms contributing to increased risk for emotional difficulties among children reared in adverse conditions and have implications for prevention and intervention.

Herpes simplex virus encephalitis in Peru: a multicentre prospective study.

Herpes simplex virus (HSV) is one of the most commonly identified infectious aetiologies of encephalitis in North America and Europe. The epidemiology of encephalitis beyond these regions, however, is poorly defined. During 2009-2012 we enrolled 313 patients in a multicentre prospective study of encephalitis in Peru, 45 (14·4%) of whom had confirmed HSV infection. Of 38 patients with known HSV type, 84% had HSV-1 and 16% had HSV-2. Patients with HSV infection were significantly more likely to present in the summer months (44·4% vs. 20·0%, P = 0·003) and have nausea (60·0% vs. 39·8%, P = 0·01) and rash (15·6% vs. 5·3%, P = 0·01) compared to patients without HSV infection. These findings highlight differences in the epidemiology and clinical presentation of HSV encephalitis outside of the Northern Hemisphere that warrant further investigation. Furthermore, there is an urgent need for improved HSV diagnostic capacity and availability of intravenous acyclovir in Peru.

Disruptions of working memory and inhibition mediate the association between exposure to institutionalization and symptoms of attention deficit hyperactivity disorder.

BACKGROUND: Young children raised in institutions are exposed to extreme psychosocial deprivation that is associated with elevated risk for psychopathology and other adverse developmental outcomes. The prevalence of attention deficit hyperactivity disorder (ADHD) is particularly high in previously institutionalized children, yet the mechanisms underlying this association are poorly understood. We investigated whether deficits in executive functioning (EF) explain the link between institutionalization and ADHD. METHOD: A sample of 136 children (aged 6-30 months) was recruited from institutions in Bucharest, Romania, and 72 never institutionalized community children matched for age and gender were recruited through general practitioners' offices. At 8 years of age, children's performance on a number of EF components (working memory, response inhibition and planning) was evaluated. Teachers completed the Health and Behavior Questionnaire, which assesses two core features of ADHD, inattention and impulsivity. RESULTS: Children with history of institutionalization had higher inattention and impulsivity than community controls, and exhibited worse performance on working memory, response inhibition and planning tasks. Lower performances on working memory and response inhibition, but not planning, partially mediated the association between early institutionalization and inattention and impulsivity symptom scales at age 8 years. CONCLUSIONS: Institutionalization was associated with decreased EF performance and increased ADHD symptoms. Deficits in working memory and response inhibition were specific mechanisms leading to ADHD in previously institutionalized children. These findings suggest that interventions that foster the development of EF might reduce risk for psychiatric problems in children exposed to early deprivation.

Multi-degree of freedom joystick for virtual reality simulation.

A modular control interface and simulated virtual reality environment were designed and created in order to determine how the kinematic architecture of a control interface affects minimally invasive surgery training. A user is able to selectively determine the kinematic configuration of an input device (number, type and location of degrees of freedom) for a specific surgical simulation through the use of modular joints and constraint components. Furthermore, passive locking was designed and implemented through the use of inflated latex tubing around rotational joints in order to allow a user to step away from a simulation without unwanted tool motion. It is believed that these features will facilitate improved simulation of a variety of surgical procedures and, thus, improve surgical skills training.

Direct mapping of hot-electron relaxation and multiplication dynamics in PbSe quantum dots.

How hot electrons relax in semiconductor quantum dots is of critical importance to many potential applications, such as solar energy conversion, light emission, and photon detection. A quantitative answer to this question has not been possible due in part to limitations of current experimental techniques in probing hot electron populations. Here we use femtosecond time-resolved two-photon photoemission spectroscopy to carry out a complete mapping in time- and energy-domains of hot electron relaxation and multiexciton generation (MEG) dynamics in lead selenide quantum dots functionalized with 1,2-ethanedithiols. We find a linear scaling law between the hot electron relaxation rate and its energy above the conduction band minimum. There is no evidence of MEG from intraband hot electron relaxation for excitation photon energy as high as three times the bandgap (3E(g)). Rather, MEG occurs in this system only from interband hot electron transitions at sufficiently high photon energies (~4E(g)).

Telomere length and early severe social deprivation: linking early adversity and cellular aging.

Accelerated telomere length attrition has been associated with psychological stress and early adversity in adults; however, no studies have examined whether telomere length in childhood is associated with early experiences. The Bucharest Early Intervention Project is a unique randomized controlled trial of foster care placement compared with continued care in institutions. As a result of the study design, participants were exposed to a quantified range of time in institutional care, and represented an ideal population in which to examine the association between a specific early adversity, institutional care and telomere length. We examined the association between average relative telomere length, telomere repeat copy number to single gene copy number (T/S) ratio and exposure to institutional care quantified as the percent of time at baseline (mean age 22 months) and at 54 months of age that each child lived in the institution. A significant negative correlation between T/S ratio and percentage of time was observed. Children with greater exposure to institutional care had significantly shorter relative telomere length in middle childhood. Gender modified this main effect. The percentage of time in institutional care at baseline significantly predicted telomere length in females, whereas the percentage of institutional care at 54 months was strongly predictive of telomere length in males. This is the first study to demonstrate an association between telomere length and institutionalization, the first study to find an association between adversity and telomere length in children, and contributes to the growing literature linking telomere length and early adversity.

Congruent and incongruent semantic context influence vowel recognition.

The influence of sentence context on the recognition of naturally spoken vowels degraded by reverberation and Gaussian noise was investigated. Target words were paired to have similar consonant sounds but different vowels (e.g., map/mop) and were embedded early in sentences which provided three types of semantic context. Fifty-eight normal-hearing, young adults were presented with sentences in which acoustic and semantic cues agreed either weakly (neutral) or strongly (congruent) or the cues strongly disagreed (incongruent). One vowel pair (/epsilon/-/ae/) was selected to be easier to recognize than the other (/a/-/ae/). Changes induced in the spectra of the vowels by degradation showed that the impact of reverberation combined with noise was quite different from either condition alone. The recognition performance of participants (n=26) for isolated word stimuli matched the predictions of the frequency analysis. In sentences the recognition of the vowel was strongly influenced by the subsequent context; performance was best with congruent context and worst with incongruent context. The deleterious impact of incongruent context was larger than the helpful impact of congruent context. Incongruent context effects were greatest in noise but were also found in quiet and in reverberation.

An infant surgical table for laser photocoagulation: ergonomic improvement analysis.

Current methods of treatment for retinopathy of prematurity, using laser photocoagulation, require surgeons to assume awkward standing positions, which can result in occupational injury. A new infant surgical table was designed for improving this surgical procedure. To quantify its benefits, an ergonomic comparison of the standard and modified procedures was carried out, using specialized checklists, Nordic Musculoskeletal Questionnaires, and analysis of videotaped procedures using an Ovako Working Posture Analysing System method. Analysis of the typical laser photocoagulation procedure revealed a high risk for cumulative trauma disorders. The majority of the risk factors were lowered considerably with use of the new table. Improvement was largely due to the new table allowing seated postures during surgery, relieving muscular stress on the back, shoulders and legs. This study demonstrates risk reduction through engineering design of new medical devices, and illustrates how combining different assessment approaches can help evaluate ergonomic impact of medical technologies.

An outbreak of post-cataract surgery endophthalmitis caused by Pseudomonas aeruginosa.

OBJECTIVE: Infectious endophthalmitis is among the most serious complications of cataract surgery. Gram-negative bacteria, including Pseudomonas aeruginosa, are responsible for less than 30% of cases; however, their rapidity of infection and virulence often results in poor visual outcome despite prompt antibiotic treatment. The purpose of this study was to investigate an outbreak of post-cataract surgery P. aeruginosa endophthalmitis in India. DESIGN: Hospital-based case series. PARTICIPANTS: Twenty patients with acute postoperative endophthalmitis who underwent cataract surgery at one of the peripheral centers of Joseph Eye Hospital, Tiruchirapalli, Tamil Nadu, India, from February 23 to April 2, 2008. INTERVENTIONS: Vitreous aspirates and environmental surveillance specimens were inoculated for culture. Antibiotic susceptibility testing was performed by agar diffusion method. Polymerase chain reaction (PCR) with enterobacterial repetitive intergenic consensus (ERIC) primers (ERIC-PCR) was used to establish the clonal relationship between clinical and environmental isolates. MAIN OUTCOME MEASURES: Post-cataract surgery P. aeruginosa endophthalmitis. RESULTS: Pseudomonas aeruginosa was isolated from 20 eyes with postoperative endophthalmitis, the phacoemulsifier's internal tubes, the povidone-iodine solution, and the operating theater air-conditioning system. All strains were multidrug-resistant to cefazolin, chloramphenicol, tetracycline, aminoglycosides, and fluoroquinolones; conversely, most of them were susceptible to polymyxin B. Polymerase chain reaction with enterobacterial repetitive intergenic consensus primers disclosed 2 major clusters: six genetically identical clinical isolates shared 94% of similarity with the air-conditioning isolate; 11 other clinical isolates had 88% of similarity with the former strain. Despite the prompt use of intravitreal antibiotics, 10 patients had evisceration or phthisis of the affected eye. CONCLUSIONS: The outcome of cataract surgery-related P. aeruginosa endophthalmitis is poor. The detection of multidrug-resistant isolates is a serious problem, jeopardizing an appropriate choice of treatment. Polymerase chain reaction with enterobacterial repetitive intergenic consensus results strongly suggest that the main source of infection in this outbreak was the contaminated air-conditioning system. Polymerase chain reaction with enterobacterial repetitive intergenic consensus is an inexpensive, fast, reproducible, and discriminatory DNA typing tool for effective epidemiologic surveillance of clinical and environmental isolates of P. aeruginosa.

Fibrinous anterior uveitis following laser in situ keratomileusis.

A 29-year-old woman who underwent laser in situ keratomileusis (LASIK) for myopic astigmatism in both eyes presented with severe pain, photophobia and decreased visual acuity in the left eye eight days after surgery. Examination revealed severe anterior uveitis with fibrinous exudates in the anterior chamber, flap edema and epithelial bullae. Laboratory investigations for uveitis were negative and the patient required systemic and intensive topical steroids with cycloplegics to control the inflammation. This case demonstrates that severe anterior uveitis may develop after LASIK and needs prompt and vigorous management for resolution.

Fusarium head blight severity and deoxynivalenol concentration in wheat in response to Gibberella zeae inoculum concentration.

The relationship between inoculum dose and resulting disease levels and deoxynivalenol (DON) accumulation in the Fusarium head blight (FHB) of wheat pathosystem was examined under controlled conditions. Greenhouse-grown spring wheat plants were inoculated at flowering with suspensions that varied in Gibberella zeae macroconidia concentration. The spikes were bagged for 72 h to promote infection and plants were then kept under ambient greenhouse conditions and disease allowed to develop. Spikes were rated at 15 days after inoculation for disease incidence and severity, removed from the greenhouse, and dried. DON concentration was determined in grain-only and whole-spike samples for each inoculation treatment. Regression analysis was used to evaluate the mathematical relationship between inoculum dose and the (i) disease metrics or (ii) DON concentration. Both disease incidence and severity were found to increase sharply in relation to inoculum concentration until an asymptote was reached. In both instances, a negative exponential function was found to best explain this relationship. By contrast, DON concentration in both grain-only and whole-spike tissues increased with additional inoculum. These relationships were best explained with linear functions for both sample types, although DON accumulation increased at a greater rate in whole-spike tissue. The functions were evaluated further using data collected from unrelated field studies and, although not particularly consistent, provided reasonably accurate predictions in growing seasons when the environment was only moderately favorable for FHB.

Plasticity of face processing in infancy.

Experience plays a crucial role for the normal development of many perceptual and cognitive functions, such as speech perception. For example, between 6 and 10 months of age, the infant's ability to discriminate among native speech sounds improves, whereas the ability to discriminate among foreign speech sounds declines. However, a recent investigation suggests that some experience with non-native languages from 9 months of age facilitates the maintenance of this ability at 12 months. Nelson has suggested that the systems underlying face processing may be similarly sculpted by experience with different kinds of faces. In the current investigation, we demonstrate that, in human infants between 6 and 9 months of age, exposure to non-native faces, in this case, faces of Barbary macaques (Macaca sylvanus), facilitates the discrimination of monkey faces, an ability that is otherwise lost around 9 months of age. These data support, and further elucidate, the role of early experience in the development of face processing.

Direct detection of a microlens in the Milky Way.

The nature of dark matter remains mysterious, with luminous material accounting for at most approximately 25 per cent of the baryons in the Universe. We accordingly undertook a survey looking for the microlensing of stars in the Large Magellanic Cloud (LMC) to determine the fraction of Galactic dark matter contained in massive compact halo objects (MACHOs). The presence of the dark matter would be revealed by gravitational lensing of the light from an LMC star as the foreground dark matter moves across the line of sight. The duration of the lensing event is the key observable parameter, but gives non-unique solutions when attempting to estimate the mass, distance and transverse velocity of the lens. The survey results to date indicate that between 8 and 50 per cent of the baryonic mass of the Galactic halo is in the form of MACHOs (ref. 3), but removing the degeneracy by identifying a lensing object would tighten the constraints on the mass in MACHOs. Here we report a direct image of a microlens, revealing it to be a nearby low-mass star in the disk of the Milky Way. This is consistent with the expected frequency of nearby stars acting as lenses, and demonstrates a direct determination of a lens mass from a microlensing event. Complete solutions such as this for halo microlensing events will probe directly the nature of the MACHOs.

Crystal structure of the TRANCE/RANKL cytokine reveals determinants of receptor-ligand specificity.

RANK, the receptor activator of NF-kappaB, and its ligand RANKL (initially termed TRANCE, also termed ODF and OPGL), are a TNF superfamily receptor-ligand pair that govern the development and function of osteoclasts, lymphoid tissue, and mammary epithelium. While TNF family cytokines share a common structural scaffold, individual receptor-ligand pairs associate with high specificity. Given the low level of amino acid conservation among members of the TNF superfamily, the means by which these molecules achieve specificity cannot be completely understood without knowledge of their three-dimensional structures. To determine the elements of RANKL that mediate RANK activation, we have crystallized the ectodomain of murine RANKL and solved its structure to a resolution of 2.6 A. RANKL self-associates as a homotrimer with four unique surface loops that distinguish it from other TNF family cytokines. Mutagenesis of selected residues in these loops significantly modulates RANK activation, as evidenced by in vitro osteoclastogenesis, thereby establishing their necessity in mediating the biological activities of RANKL. Such structural determinants of RANKL-RANK specificity may be of relevance in the pharmacologic design of compounds to ameliorate osteopenic disorders of bone.

Mechanisms of postnatal neurobiological development: implications for human development.

This review focuses on the postnatal neuroanatomical changes that arise during the first years of human life. Development is characterized by 2 major organizational periods. The first period begins at conception and includes the major histogenetic events such as neurulation, proliferation, migration, and differentiation. It has been proposed that these events may be controlled by genetic and epigenetic events, which give rise to neural structures that are amenable to external influence. The second period is a time of reorganization in the human cortex. These events occur during gestation and continue postnatally, possibly through the 2nd decade of life. This stage is characterized by dendritic and axonal growth, synapse production, neuronal and synaptic pruning, and changes in neurotransmitter sensitivity. Although the initiation of these events is influenced by endogenous signals, further neural maturation is primarily influenced by exogenous signals. To illustrate both the progressive and regressive events during the postnatal period, we use examples from the development of the human cortex.