Distant heterotopic callosal connections to premotor cortex in non-human primates

Cortico-cortical connectivity has become a major focus of neuroscience in the last decade but most of the connectivity studies focused on intrahemispheric circuits. Little has been reported about information acquired and processed in the premotor cortex and its functional connection with its homotopic counterpart in the opposite hemisphere via the corpus callosum. In non-human primates (macaques) lateralization is not well documented and its exact role is still unknown. The present study confirms in two macaques the existence of homotopic contralateral projections and completes the picture by further exploring heterotopic (non-motor) callosal projections. This was tested by injecting retrograde tracers in the premotor cortical areas PMv and PMd (targets). Our method consisted of identifying the connections with all the homo- and heterotopic cortical areas located in the contralateral hemisphere. The results showed that PMd and PMv receive multiple low-density labeled inputs from the opposite heterotopic prefrontal, parietal, motor, insular and temporal regions. Such unexpected collection of transcallosal inputs from heterotopic areas suggests that the premotor areas communicate with other modalities through long distance low-density networks which could have important implications in the understanding of sensorimotor and multimodal integration

Correction of hyperglycemia after surgery for diabetic foot infection and its association with clinical outcomes

Objective: Constantly high glycemia levels might influence outcomes in the management of patients undergoing surgery for diabetic foot infections (DFI). In our center for DFI, we performed a case-control study using a multivariate Cox regression model. Patients developing a new DFI could participate in the study several times. Results: Among 1013 different DFI episodes in 586 individual adult patients (type I diabetes 148 episodes [15%], 882 [87%] with osteomyelitis; median antibiotic therapy of 21 days), professional diabetes counselling was provided by a specialized diabetes nurse in 195 episodes (19%). At admission, blood glucose levels were elevated in 110 episodes (11%). Treatments normalized glycemia on postoperative day 3 in 353 episodes (35%) and on day 7 for 321 (32%) episodes. Glycemia levels entirely normalized for 367 episodes (36%) until the end of hospitalization. Overall, treatment of DFI episodes failed in 255 of 1013 cases (25%), requiring surgical revision. By multivariate analysis, neither the provision of diabetes counseling, nor attaining normalizations of daily glycemic levels at day 3, day 7, or overall, influenced the ultimate incidence of clinical failures. Thus, the rapidity or success of achieving normoglycemia do not appear to influence the risk of treatment failure for operated DFI episodes. Keywords: Diabetic foot infections; Glycemia; Insulin therapy; Outcomes; Surger

Impact of Selection and Demography on the Diffusion of Lactase Persistence

BACKGROUND: The lactase enzyme allows lactose digestion in fresh milk. Its activity strongly decreases after the weaning phase in most humans, but persists at a high frequency in Europe and some nomadic populations. Two hypotheses are usually proposed to explain the particular distribution of the lactase persistence phenotype. The gene-culture coevolution hypothesis supposes a nutritional advantage of lactose digestion in pastoral populations. The calcium assimilation hypothesis suggests that carriers of the lactase persistence allele(s) (LCT*P) are favoured in high-latitude regions, where sunshine is insufficient to allow accurate vitamin-D synthesis. In this work, we test the validity of these two hypotheses on a large worldwide dataset of lactase persistence frequencies by using several complementary approaches. METHODOLOGY: We first analyse the distribution of lactase persistence in various continents in relation to geographic variation, pastoralism levels, and the genetic patterns observed for other independent polymorphisms. Then we use computer simulations and a large database of archaeological dates for the introduction of domestication to explore the evolution of these frequencies in Europe according to different demographic scenarios and selection intensities. CONCLUSIONS: Our results show that gene-culture coevolution is a likely hypothesis in Africa as high LCT*P frequencies are preferentially found in pastoral populations. In Europe, we show that population history played an important role in the diffusion of lactase persistence over the continent. Moreover, selection pressure on lactase persistence has been very high in the North-western part of the continent, by contrast to the South-eastern part where genetic drift alone can explain the observed frequencies. This selection pressure increasing with latitude is highly compatible with the calcium assimilation hypothesis while the gene-culture coevolution hypothesis cannot be ruled out if a positively selected lactase gene was carried at the front of the expansion wave during the Neolithic transition in Europe

Repenser le consentement éclairé dans le contexte des analyses génétiques par séquençage à haut débit

Le séquençage à haut débit permet l'analyse de grands panels de gènes, de l'exome ou du génome, facilitant considérablement le diagnostic des maladies mendéliennes. Cependant, cette technique aboutit également à des résultats inattendus au sujet desquels il est crucial que les patients soient informés. Le présent travail s'intéresse au consentement éclairé des patients entreprenant une analyse par séquençage à haut débit. Nous avons, d'une part, proposé une catégorisation des résultats inattendus, basée sur leur actionnabilité. Puis, nous avons discuté des conditions rendant le choix des patients autonome et avons argumenté pour le recours à des définitions de l'autonomie plus exigeantes que celle mise en œuvre par le droit suisse, comme la version de Gerald Dworkin et de Joseph Raz. Finalement, une étude empirique a confirmé et élargi notre catégorisation de l'actionnabilité et a apporté des pistes pour améliorer le respect de l'autonomie des patients en pratique clinique

Dysphagia in the intensive care unit in Switzerland (DICE) - results of a national survey on the current standard of care.

INTRODUCTION Oropharyngeal dysphagia (OD) is often observed in critically ill patients. In most affected patients OD persists throughout hospital stay and negatively impacts on clinical outcomes. Here we systematically explore routine clinical practice standards for recognition/screening, diagnosis and treatment of OD in accredited Swiss ICUs. METHODS An online, 23-item questionnaire-based survey was performed to investigate current standards of care for OD in Switzerland (DICE). All (n = 49) accredited Swiss teaching hospitals providing specialist training for adult intensive care medicine were contacted. Senior intensivists were interviewed on how they would screen for, diagnose and treat OD in the ICU. RESULTS The total response rate was 75.5%, with information available on all tertiary care academic centres. 67.6% (25/37) of institutions stated that they have established standard operating procedures for OD using a mostly sequential diagnostic approach (86.5%, 32/37). In 75.7% (28/37) of institutions, OD confirmation is performed without the use of instrumental techniques such as flexible (or fibre-endoscopic) evaluation of swallowing (FEES). Presumed key risk factors for OD were admission for acute neurological illness, long-term mechanical ventilation, ICU-acquired weakness and pre-existing neurological disease. Reported presumed OD-related complications typically include aspiration-induced pneumonia, increased rates of both reintubation and tracheostomy and increased ICU readmission rates. CONCLUSIONS Many Swiss ICUs have established standard operating procedures, with most using sequential clinical approaches to assess ICU patients at risk of dysphagia. OD confirmation is mostly performed using non-instrumental techniques. In general, it appears that awareness of OD and ICU educational curricula can be further optimised

Risk factors for dysphagia in ICU patients following invasive mechanical ventilation.

BACKGROUND Dysphagia is common and independently predicts death in ICU patients. Risk factors for dysphagia are largely unknown with sparse data available from mostly small cohorts without systematic dysphagia screening. RESEARCH QUESTION What are the key risk factors for dysphagia in ICU patients post invasive mechanical ventilation? STUDY DESIGN AND METHODS Post-hoc analysis of data from a monocentric prospective observational study ("DYnAMICS") using comprehensive statistical models to identify potential risk factors for post-extubation dysphagia. 933 primary admissions of adult medical-surgical ICU patients (median age 65 years [IQR 54-73], n=666 (71%) male) were investigated in a tertiary care academic centre. Patients received systematic bedside screening for dysphagia within 3 hours post extubation. Dysphagia screening positivity (n=116) was followed within 24 hours by a confirmatory exam. RESULTS After adjustment for confounders, baseline neurological disease (OR 4.45, 95%-CI: 2.74-7.24, p<0.01), emergency admission (OR 2.04, 95%-CI: 1.15-3.59, p<0.01), days on mechanical ventilation (OR 1.19, 95%-CI: 1.06-1.34, p<0.01), days on renal replacement therapy (OR 1.1, 95%-CI: 1-1.23, p=0.03), and disease severity (APACHE II score within first 24 hours; OR 1.03, 95%-CI: 0.99-1.07, p<0.01) remained independent risk factors for dysphagia post extubation. Increased Body Mass Index reduced the risk for dysphagia (6% per step increase, OR 0.94, 95%-CI: 0.9-0.99, p=0.03). INTERPRETATION In ICU patients, baseline neurological disease, emergency admission and duration of invasive mechanical ventilation appeared as prominent independent risk factors for dysphagia. As all ICU patients post mechanical ventilation should be considered at risk for dysphagia, systematic screening for dysphagia is recommended in respective critically ill patients. CLINICAL TRIAL REGISTRATION clinicaltrials.gov (NCT02333201)

Informed Consent and the Disclosure of Clinical Results to Research Participants

ISSN:1526-5161ISSN:1536-007

Clinical and Radiological Outcomes after Knee Arthroplasty with Patient-Specific versus Off-the-Shelf Knee Implants: A Systematic Review

Customised, patient-specific implants (PSI) manufactured based on computed tomography data are intended to improve the clinical outcome by restoring more natural knee kinematics as well as providing a better fit and a more precise positioning. The aim of this systematic review is to investigate the effect of these PSI on the clinical and radiological outcome compared to standard, off-the-shelf (OTS) implants. Thirteen comparative studies including a total of 2127 knee implants were identified. No significant differences in clinical outcome assessed with the range of motion, the Knee Society Score (KSS), and the Forgotten Joint Score (FJS-12) were found between PSI and OTS implants. PSI showed fewer outliers from the neutral limb axis and a better implant fit and positioning. Whether these radiological differences lead to long-term advantages in terms of implant survival cannot be answered based on the current data. Patients receiving PSI could be discharged home earlier at the same or at an even lower total cost. The effective overall superiority of PSI has yet to be proven in long-term studies

Defining categories of actionability for secondary findings in next-generation sequencing

Next-generation sequencing is increasingly used in clinical practice for the diagnosis of Mendelian diseases. Because of the high likelihood of secondary findings associated with this technique, the process of informing patients is beset with new challenges. One of them is regarding the type of secondary findings that ought to be disclosed to patients. The aim of this research is to propose a practical implementation of the notion of actionability, a common criteria justifying the disclosure of secondary findings but whose interpretation varies greatly among professionals. We distinguish three types of actionability corresponding to (1) well-established medical actions, (2) patient-initiated health-related actions and (3) life-plan decisions. We argue that actionability depends on the characteristics of the mutation or gene and on the values of patients. In discussing the return of secondary findings, it is important that the physician tries to get an impression of the specific situation and values of patients. Regarding variants of uncertain clinical significance in actionable genes, we found that different understandings of autonomy lead to different conclusions and that, for some of them, it may be legitimate to refrain from returning uncertain information