Cortico-thalamocortical interactions for learning, memory and decision-making

This is the final version. Available on open access from Wiley via the DOI in this recordThe thalamus and cortex are interconnected both functionally and anatomically and share a common developmental trajectory. Interactions between the mediodorsal thalamus (MD) and different parts of the prefrontal cortex are essential in cognitive processes, such as learning and adaptive decision-making. Cortico-thalamocortical interactions involving other dorsal thalamic nuclei, including the anterior thalamus and pulvinar, also influence these cognitive processes. Our work, and that of others, indicates a crucial influence of these interdependent cortico-thalamocortical neural networks that contributes actively to the processing of information within the cortex. Each of these thalamic nuclei also receives potent subcortical inputs that are likely to provide additional influences on their regulation of cortical activity. Here, we highlight our current neuroscientific research aimed at establishing when cortico-MD thalamocortical neural network communication is vital within the context of a rapid learning and memory discrimination task. We are collecting evidence of MD-prefrontal cortex neural network communication in awake, behaving male rhesus macaques. Given the prevailing evidence, further studies are needed to identify both broad and specific mechanisms that govern how the MD, anterior thalamus and pulvinar cortico-thalamocortical interactions support learning, memory and decision-making. Current evidence shows that the MD (and the anterior thalamus) are crucial for frontotemporal communication, and the pulvinar is crucial for frontoparietal communication. Such work is crucial to advance our understanding of the neuroanatomical and physiological bases of these brain functions in humans. In turn, this might offer avenues to develop effective treatment strategies to improve the cognitive deficits often observed in many debilitating neurological disorders and diseases and in neurodegeneration.Wellcome Trus

Variable cardiac responses in rhesus macaque monkeys after discrete mediodorsal thalamus manipulations

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability; All data analysed during this study are included in this article.The control of some physiological parameters, such as the heart rate, is known to have a role in cognitive and emotional processes. Cardiac changes are also linked to mental health issues and neurodegeneration. Thus, it is not surprising that many of the brain structures typically associated with cognition and emotion also comprise a circuit-the central automatic network-responsible for the modulation of cardiovascular output. The mediodorsal thalamus (MD) is involved in higher cognitive processes and is also known to be connected to some of the key neural structures that regulate cardiovascular function. However, it is unclear whether the MD has any role in this circuitry. Here, we show that discrete manipulations (microstimulation during anaesthetized functional neuroimaging or localized cytotoxin infusions) to either the magnocellular or the parvocellular MD subdivisions led to observable and variable changes in the heart rate of female and male rhesus macaque monkeys. Considering the central positions that these two MD subdivisions have in frontal cortico-thalamocortical circuits, our findings suggest that MD contributions to autonomic regulation may interact with its identified role in higher cognitive processes, representing an important physiological link between cognition and emotion.Wellcome TrustFWOCost Action Primtrai

Medicine and Ethics

A new world has probably emerged through the progression of technology which has led to significant debates on social, cultural, legal, and ethical issues, especially in the biomedical field in this century. Application of physician-patient relationship, principles of pluralism, autonomy, democracy, human dignity, and human rights is being challenged within the medicine and health-care system of today. Development of technology-based remedies has fostered greater degrees of medicalization. Hence, the automatic application of such technologies risks distorting the nature of medicine. To be sure, there is a cultural shift that is affecting the society that is increasingly unable to adapt to traditional legal systems. This cultural shift, perhaps, demands new ethics. This entry aims to evaluate the gap between traditional deontological nature of medicine and the emerging new ethics and assess why bioethical reflection is needed

Moderately overweight and obese patients in general practice: a population based survey

BACKGROUND: Obesity is a main threat to public health in the Western world and is associated with diseases such as diabetes mellitus and coronary heart diseases. Up to now a minority of research studied the relation between obesity and the use of primary health care. In the Netherlands the general practitioner (GP) is the main primary health care provider. The objective of this article is to evaluate GP consultation and prescription of drugs in moderate and severely overweight (obese) persons in the Netherlands. METHODS: Data were used from a representative survey of morbidity in Dutch general practice in 2001. Our study sample consisted of 8,944 adult respondents (18+ years) who participated in an extensive health interview. Interview data were linked to morbidity and prescription registration data from 95 general practices where respondents were listed. Body mass index (BMI) was calculated using self-reported height and weight. Analyses were controlled for clustering within practices as well as for socio-demographic and life style characteristics. RESULTS: Obesity (BMI ≥ 30 kg/m2) was observed in 8.9% of men and 12.4% of women; for moderate overweight (BMI 25-<30 kg/m2) these percentages were 42.2% and 30.4% respectively. Obese men and women were more likely to consult their GP than persons without overweight. This especially holds for diseases of the endocrine system, the cardiovascular system, the musculoskeletal system, the gastro-intestinal system, and skin problems. Related to this, obese men and women were more likely to receive drugs for the cardiovascular system, the musculoskeletal system, alimentary tract and metabolism (including, for example, antidiabetics), and dermatologicals, but also antibiotics and drugs for the respiratory system. For moderately overweight men and women (BMI 25-<30 kg/m2) smaller but significant differences were found for diseases of the endocrine system, the cardiovascular system, and the musculoskeletal system. CONCLUSION: Obesity increases the workload of Dutch general practitioners and the use of prescribed medication. The current increase in the prevalence of obesity will further increase the use of health care and related costs. Since a large majority of Dutch persons visit their GP over the course of one year, GPs' potential role in effective prevention strategies cannot be denied

Pediatric differentiated thyroid carcinoma in stage I: risk factor analysis for disease free survival

<p>Abstract</p> <p>Background</p> <p>To examine the outcomes and risk factors in pediatric differentiated thyroid carcinoma (DTC) patients who were defined as TNM stage I because some patients develop disease recurrence but treatment strategy for such stage I pediatric patients is still controversial.</p> <p>Methods</p> <p>We reviewed 57 consecutive TNM stage I patients (15 years or less) with DTC (46 papillary and 11 follicular) who underwent initial treatment at Ito Hospital between 1962 and 2004 (7 males and 50 females; mean age: 13.1 years; mean follow-up: 17.4 years). Clinicopathological results were evaluated in all patients. Multivariate analysis was performed to reveal the risk factors for disease-free survival (DFS) in these 57 patients.</p> <p>Results</p> <p>Extrathyroid extension and clinical lymphadenopathy at diagnosis were found in 7 and 12 patients, respectively. Subtotal/total thyroidectomy was performed in 23 patients, modified neck dissection in 38, and radioactive iodine therapy in 10. Pathological node metastasis was confirmed in 37 patients (64.9%). Fifteen patients (26.3%) exhibited local recurrence and 3 of them also developed metachronous lung metastasis. Ten of these 15 achieved disease-free after further treatments and no patients died of disease. In multivariate analysis, male gender (p = 0.017), advanced tumor (T3, 4a) stage (p = 0.029), and clinical lymphadenopathy (p = 0.006) were risk factors for DFS in stage I pediatric patients.</p> <p>Conclusion</p> <p>Male gender, tumor stage, and lymphadenopathy are risk factors for DFS in stage I pediatric DTC patients. Aggressive treatment (total thyroidectomy, node dissection, and RI therapy) is considered appropriate for patients with risk factors, whereas conservative or stepwise approach may be acceptable for other patients.</p

RNAi-Based Functional Genomics Identifies New Virulence Determinants in Mucormycosis

Mucorales are an emerging group of human pathogens that are responsible for the lethal disease mucormycosis. Unfortunately, functional studies on the genetic factors behind the virulence of these organisms are hampered by their limited genetic tractability, since they are reluctant to classical genetic tools like transposable elements or gene mapping. Here, we describe an RNAi-based functional genomic platform that allows the identification of new virulence factors through a forward genetic approach firstly described in Mucorales. This platform contains a whole-genome collection of Mucor circinelloides silenced transformants that presented a broad assortment of phenotypes related to the main physiological processes in fungi, including virulence, hyphae morphology, mycelial and yeast growth, carotenogenesis and asexual sporulation. Selection of transformants with reduced virulence allowed the identification of mcplD, which encodes a Phospholipase D, and mcmyo5, encoding a probably essential cargo transporter of the Myosin V family, as required for a fully virulent phenotype of M. circinelloides. Knock-out mutants for those genes showed reduced virulence in both Galleria mellonella and Mus musculus models, probably due to a delayed germination and polarized growth within macrophages. This study provides a robust approach to study virulence in Mucorales and as a proof of concept identified new virulence determinants in M. circinelloides that could represent promising targets for future antifungal therapies

Towards successful coordination of electronic health record based-referrals: a qualitative analysis

<p>Abstract</p> <p>Background</p> <p>Successful subspecialty referrals require considerable coordination and interactive communication among the primary care provider (PCP), the subspecialist, and the patient, which may be challenging in the outpatient setting. Even when referrals are facilitated by electronic health records (EHRs) (<it>i.e</it>., e-referrals), lapses in patient follow-up might occur. Although compelling reasons exist why referral coordination <it>should </it>be improved, little is known about which elements of the complex referral coordination process should be targeted for improvement. Using Okhuysen & Bechky's coordination framework, this paper aims to understand the barriers, facilitators, and suggestions for improving communication and coordination of EHR-based referrals in an integrated healthcare system.</p> <p>Methods</p> <p>We conducted a qualitative study to understand coordination breakdowns related to e-referrals in an integrated healthcare system and examined work-system factors that affect the timely receipt of subspecialty care. We conducted interviews with seven subject matter experts and six focus groups with a total of 30 PCPs and subspecialists at two tertiary care Department of Veterans Affairs (VA) medical centers. Using techniques from grounded theory and content analysis, we identified organizational themes that affected the referral process.</p> <p>Results</p> <p>Four themes emerged: lack of an institutional referral policy, lack of standardization in certain referral procedures, ambiguity in roles and responsibilities, and inadequate resources to adapt and respond to referral requests effectively. Marked differences in PCPs' and subspecialists' communication styles and individual mental models of the referral processes likely precluded the development of a <it>shared </it>mental model to facilitate coordination and successful referral completion. Notably, very few barriers related to the EHR were reported.</p> <p>Conclusions</p> <p>Despite facilitating information transfer between PCPs and subspecialists, e-referrals remain prone to coordination breakdowns. Clear referral policies, well-defined roles and responsibilities for key personnel, standardized procedures and communication protocols, and adequate human resources must be in place before implementing an EHR to facilitate referrals.</p

The impact of rheumatoid foot on disability in Colombian patients with rheumatoid arthritis

<p>Abstract</p> <p>Background</p> <p>Alterations in the feet of patients with rheumatoid arthritis (RA) are a cause of disability in this population. The purpose of this research was to evaluate the impact that foot impairment has on the patients' global quality of life (QOL) based on validated scales and its relationship to disease activity.</p> <p>Methods</p> <p>This was a cross-sectional study in which 95 patients with RA were enrolled. A complete physical examination, including a full foot assessment, was done. The Spanish versions of the Health Assessment Questionnaire (HAQ) Disability Index and of the Disease Activity Score (DAS 28) were administered. A logistic regression model was used to analyze data and obtain adjusted odds ratios (AORs).</p> <p>Results</p> <p>Foot deformities were observed in 78 (82%) of the patients; hallux valgus (65%), medial longitudinal arch flattening (42%), claw toe (lesser toes) (39%), dorsiflexion restriction (tibiotalar) (34%), cock-up toe (lesser toes) (25%), and transverse arch flattening (25%) were the most frequent. In the logistic regression analysis (adjusted for age, gender and duration of disease), forefoot movement pain, subtalar movement pain, tibiotalar movement pain and plantarflexion restriction (tibiotalar) were strongly associated with disease activity and disability. The positive squeeze test was significantly associated with disability risk (AOR = 6,3; 95% CI, 1.28–30.96; P = 0,02); hallux valgus, and dorsiflexion restriction (tibiotalar) were associated with disease activity.</p> <p>Conclusion</p> <p>Foot abnormalities are associated with active joint disease and disability in RA. Foot examinations provide complementary information related to the disability as an indirect measurement of quality of life and activity of disease in daily practice.</p