Phenotyping Down syndrome: discovery and predictive modelling with electronic medical records.

BACKGROUND: Individuals with Down syndrome (DS) have a heightened risk for various co-occurring health conditions, including congenital heart disease (CHD). In this two-part study, electronic medical records (EMRs) were leveraged to examine co-occurring health conditions among individuals with DS (Study 1) and to investigate health conditions linked to surgical intervention among DS cases with CHD (Study 2). METHODS: De-identified EMRs were acquired from Vanderbilt University Medical Center and facilitated creating a cohort of N = 2282 DS cases (55% females), along with comparison groups for each study. In Study 1, DS cases were one-by-two sex and age matched with samples of case-controls and of individuals with other intellectual and developmental difficulties (IDDs). The phenome-disease association study (PheDAS) strategy was employed to reveal co-occurring health conditions in DS versus comparison groups, which were then ranked for how often they are discussed in relation to DS using the PubMed database and Novelty Finding Index. In Study 2, a subset of DS individuals with CHD [N = 1098 (48%)] were identified to create longitudinal data for N = 204 cases with surgical intervention (19%) versus 204 case-controls. Data were included in predictive models and assessed which model-based health conditions, when more prevalent, would increase the likelihood of surgical intervention. RESULTS: In Study 1, relative to case-controls and those with other IDDs, co-occurring health conditions among individuals with DS were confirmed to include heart failure, pulmonary heart disease, atrioventricular block, heart transplant/surgery and primary pulmonary hypertension (circulatory); hypothyroidism (endocrine/metabolic); and speech and language disorder and Alzheimer's disease (neurological/mental). Findings also revealed more versus less prevalent co-occurring health conditions in individuals with DS when comparing with those with other IDDs. Findings with high Novelty Finding Index were abnormal electrocardiogram, non-rheumatic aortic valve disorders and heart failure (circulatory); acid-base balance disorder (endocrine/metabolism); and abnormal blood chemistry (symptoms). In Study 2, the predictive models revealed that among individuals with DS and CHD, presence of health conditions such as congestive heart failure (circulatory), valvular heart disease and cardiac shunt (congenital), and pleural effusion and pulmonary collapse (respiratory) were associated with increased likelihood of surgical intervention. CONCLUSIONS: Research efforts using EMRs and rigorous statistical methods could shed light on the complexity in health profile among individuals with DS and other IDDs and motivate precision-care development.

The action of curcumin against damage resulting from cerebral stroke: A systematic review.

Stroke is the second leading cause of morbidity and mortality globally. Treatments for stroke are limited, and preventive treatments are scarce. Curcumin (CUR) has several biological effects, as described in the literature, which highlight its antioxidant and neuroprotective effects. Therefore, this qualitative systematic review aimed to investigate the effects of CUR on damage caused by stroke in rodent models. A systematic search was performed on three databases PubMed, Scopus, and Web of Science. In addition, the risk-of-bias and quality of the studies were assessed using SYRCLE and Collaborative Approach for Meta-Analysis and Review of Animal Data from Experimental Studies, respectively. The selection, inclusion, and exclusion criteria were established by the authors. At the end of our systematic search of the three databases, we found a total of 728 articles. After excluding duplicates and triplicates and reading the abstracts, keywords, and full texts, 53 articles were finally included in this systematic review. CUR exerts several beneficial effects against the damage caused by both ischemic and hemorrhagic stroke, via different pathways. However, because of its low bioavailability, Free-form CUR only exerted significant effects when it was administered at high concentrations. In contrast, when CUR was administered using nanostructured systems, positive responses were observed even at low concentrations. The mechanisms of action of CUR, free or in nanostructure, are extremely important for the recovery of injured brain tissue after a stroke; CUR has neuroprotective, antioxidant, anti-inflammatory, and anti-apoptotic effects and helps to maintain the integrity of the blood-brain barrier. Finally, we concluded that CUR presents an extremely important and significant response profile against the damage caused by stroke, making it a possible therapeutic candidate for individuals affected by this disease.

Long-term health sequelae and quality of life at least 6 months after infection with SARS-CoV-2: design and rationale of the COVIDOM-study as part of the NAPKON population-based cohort platform (POP).

PURPOSE: Over the course of COVID-19 pandemic, evidence has accumulated that SARS-CoV-2 infections may affect multiple organs and have serious clinical sequelae, but on-site clinical examinations with non-hospitalized samples are rare. We, therefore, aimed to systematically assess the long-term health status of samples of hospitalized and non-hospitalized SARS-CoV-2 infected individuals from three regions in Germany. METHODS: The present paper describes the COVIDOM-study within the population-based cohort platform (POP) which has been established under the auspices of the NAPKON infrastructure (German National Pandemic Cohort Network) of the national Network University Medicine (NUM). Comprehensive health assessments among SARS-CoV-2 infected individuals are conducted at least 6 months after the acute infection at the study sites Kiel, Würzburg and Berlin. Potential participants were identified and contacted via the local public health authorities, irrespective of the severity of the initial infection. A harmonized examination protocol has been implemented, consisting of detailed assessments of medical history, physical examinations, and the collection of multiple biosamples (e.g., serum, plasma, saliva, urine) for future analyses. In addition, patient-reported perception of the impact of local pandemic-related measures and infection on quality-of-life are obtained. RESULTS: As of July 2021, in total 6813 individuals infected in 2020 have been invited into the COVIDOM-study. Of these, about 36% wished to participate and 1295 have already been examined at least once. CONCLUSION: NAPKON-POP COVIDOM-study complements other Long COVID studies assessing the long-term consequences of an infection with SARS-CoV-2 by providing detailed health data of population-based samples, including individuals with various degrees of disease severity. TRIAL REGISTRATION: Registered at the German registry for clinical studies (DRKS00023742).

Imaging of spindle cell lipoma.

AIM: To review the evaluation, diagnosis, and treatment of spindle cell lipoma (SCL) with emphasis on the location of these tumours and the spectrum of magnetic resonance imaging (MRI) and computed tomography (CT) appearances. MATERIALS AND METHODS: The MRI and CT findings of 27 histopathologically proven SCLs were evaluated retrospectively. Imaging features evaluated included margins, percentage visible fat, MRI signal characteristics, oedema, and contrast enhancement patterns. RESULTS: Patient ages ranged from 18 to 80 years with an average age of 56.5 years. Men were affected twice as frequently as women (M=18, F=9). SCLs ranged in size from 2 to 10 cm, with an average greatest dimension of 5.5 cm. Five lesions (19%) contained no visible fat on CT or MRI, and the leading differential diagnosis of high-grade soft-tissue sarcoma diagnosis was suggested by referring surgeons. Five lesions (19%) had <50% fatty areas, nine lesions (52%) demonstrated >50% but <90% fat at MRI or CT. Only three of 25 lesions (12%) had an appearance of a typical lipoma on unenhanced MRI sequences. All SCLs that were imaged with contrast medium (n = 18) demonstrated some degree of enhancement, with eight (44%) showing marked enhancement, four (22%) showing moderate, and six (33%) minimal enhancement. CONCLUSION: SCLs have considerably variable imaging appearances and may have minimal or no visible fat at MRI or CT. Imaging features may make it difficult to distinguish this benign tumour from a potentially higher-grade malignant tumour.

Population-based study on resection rates and survival in patients with colorectal liver metastasis in Norway.

BACKGROUND: Detailed knowledge about the proportion of patients with colorectal liver metastases (CLM) undergoing resection is sparse. The aim of this study was to analyse cumulative resection rates and survival in patients with CLM. METHODS: For this population-based study of patients developing CLM during 2011-2013, data were extracted from the Norwegian Patient Registry and the Cancer Registry of Norway. RESULTS: A total of 2960 patients had CLM; their median overall survival was 10·9 months. Liver resection was performed in 538 patients. The cumulative resection rate was 20·0 per cent. The cumulative resection rate was 23·3 per cent in patients aged less than 40 years, 31·1 per cent in patients aged 40-59 years, 24·7 per cent in those aged 60-74 years, 17·9 per cent in those aged 75-79 years and 4·7 per cent in patients aged 80 years or more (P < 0·001). In multivariable analysis, resection rate was associated with age, extrahepatic metastases, disease-free interval and geographical region. Overall survival after diagnosis of CLM was affected by liver resection (hazard ratio (HR) 0·54, 95 per cent c.i. 0·34 to 0·86), rectal cancer (HR 0·82, 0·74 to 0·90), metachronous disease (HR 0·66, 0·60 to 0·74), increasing age (HR 1·32, 1·28 to 1·37), region, and extrahepatic metastases (HR 1·90, 1·74 to 2·07). Three- and 4-year overall survival rates after hepatectomy were 73·2 and 54·8 per cent respectively. CONCLUSION: The cumulative resection rate in patients with CLM in Norway between 2011 and 2013 was 20 per cent. Resection rates varied across geographical regions, and with patient and disease characteristics.

[Current Status of Medical Care for Nursing Home Residents in Germany - Results of an Empirical Study]. / Zur Entwicklung der ärztlichen Versorgung in stationären Pflegeeinrichtungen ­ Ergebnisse einer empirischen Untersuchung.

Following recent studies revealing deficits in general and specialised medical care of nursing home residents in Germany, the discussion on the quality of medical care of residents in residential care facilities has intensified in the past years. As a result, political efforts have been undertaken to facilitate improvements in this context. We collected data on the health status and medical care of 778 residents from 8 nursing homes in order to investigate the current situation regarding medical care for nursing home residents in Germany. Most of them were multimorbid, taking several prescribed medications. Our results showed that about 91% of the residents had personal contact to general practitioners or internists quarterly and only 1.3% had no such contacts within a year. The frequency of contacts to other medical specialists was comparably low. For example, within a year, only 18.9% of the residents had contact to urologists; only 16.7% had contact to ophthalmologists; only 39.6% had contact to dentists and only 10.6% of the female residents had contact to gynaecologists. Despite the fact that many of the residents showed specific medical care needs, these rates were below the utilisation rates of older population groups not living in long-term care homes. This leads to the conclusion that previous efforts to optimise medical care in nursing homes were only partially successful. Well known deficits are still remaining. Considering potential consequences for residents, further and consequent actions are required to improve the general and specialised medical care in institutionalised long-term care.

Protective role of free and quercetin-loaded nanoemulsion against damage induced by intracerebral haemorrhage in rats.

Intracerebral haemorrhage (ICH) is a worldwide public health problem. Experimental studies have shown that oxidative stress plays an important role in the pathogenesis of ICH and could represent a target for its treatment. However, the blood-brain barrier is an obstacle to be overcome, as it hampers the administration of compounds to the central nervous system. In this study, we compared the effects of a quercetin-loaded nanoemulsion (QU-N) with the free form of the drug (QU-SP) in a collagenase-induced ICH rat model. Quercetin (QU) is a polyphenol that has an antioxidant effect in vitro, but due to its high lipophilicity, it has low bioavailability in vivo. In this study, animals submitted or not to ICH were treated with a single intraperitoneal QU dose (free or nanoemulsion) of 30 mg kg(-1). Motor assessment was evaluated by the open field, foot fault and beam walking behavioural tests. 72 h after surgery the haematoma size was evaluated and biochemical measurements were performed. Animals treated with QU-N had a significant improvement in the beam walking and open field tests. Also, QU-N was able to reduce the size of the haematoma, preserving the activity of glutathione S-transferase (GST), increasing GSH content, and the total antioxidant capacity. QU-SP recovered locomotor activity and increased the GSH content and the total antioxidant capacity. Thus, it can be observed that QU presented antioxidant activity in both formulations, but the incorporation into nanoemulsions increased its antioxidant effect, which was reflected in the improvement of the motor skills and in the haematoma size decrement. These results suggest that the nanoemulsion containing QU developed in this study could be promising for future studies on treatments for ICH.

Effects of using the simplified airway risk index vs usual airway assessment on unanticipated difficult tracheal intubation - a cluster randomized trial with 64,273 participants.

BACKGROUND: Unanticipated difficult intubation remains a challenge in anaesthesia. The Simplified Airway Risk Index (SARI) is a multivariable risk model consisting of seven independent risk factors for difficult intubation. Our aim was to compare preoperative airway assessment based on the SARI with usual airway assessment. METHODS: From 01.10.2012 to 31.12.2013, 28 departments were cluster-randomized to apply the SARI model or usual airway assessment. The SARI group implemented the SARI model. The Non-SARI group continued usual airway assessment, thus reflecting a group of anaesthetists' heterogeneous individual airway assessments. Preoperative prediction of difficult intubation and actual intubation difficulties were registered in the Danish Anaesthesia Database for both groups. Patients who were preoperatively scheduled for intubation by advanced techniques (e.g. video laryngoscopy; flexible optic scope) were excluded from the primary analysis. Primary outcomes were the proportions of unanticipated difficult and unanticipated easy intubation. RESULTS: A total of 26 departments (15 SARI and 11 Non-SARI) and 64 273 participants were included. In the primary analyses 29 209 SARI and 30 305 Non-SARI participants were included.In SARI departments 2.4% (696) of the participants had an unanticipated difficult intubation vs 2.4% (723) in Non-SARI departments. Odds ratio (OR) adjusted for design variables was 1.03 (95% CI: 0.77-1.38). The proportion of unanticipated easy intubation was 1.42% (415) in SARI departments vs 1.00% (302) in Non-SARI departments. Adjusted OR was 1.26 (0.68-2.34). CONCLUSIONS: Using the SARI compared with usual airway assessment we detected no statistical significant changes in unanticipated difficult- or easy intubations. CLINICAL TRIAL REGISTRATION: NCT01718561.

Reduction of Toxoplasma gondii Development Due to Inhibition of Parasite Antioxidant Enzymes by a Dinuclear Iron(III) Compound.

Toxoplasma gondii, the causative agent of toxoplasmosis, is an obligate intracellular protozoan that can infect a wide range of vertebrate cells. Here, we describe the cytotoxic effects of the dinuclear iron compound [Fe(HPCINOL)(SO4)]2-µ-oxo, in which HPCINOL is the ligand 1-(bis-pyridin-2-ylmethyl-amino)-3-chloropropan-2-ol, on T. gondii infecting LLC-MK2 host cells. This compound was not toxic to LLC-MK2 cells at concentrations of up to 200 µM but was very active against the parasite, with a 50% inhibitory concentration (IC50) of 3.6 µM after 48 h of treatment. Cyst formation was observed after treatment, as indicated by the appearance of a cyst wall, Dolichos biflorus lectin staining, and scanning and transmission electron microscopy characteristics. Ultrastructural changes were also seen in T. gondii, including membrane blebs and clefts in the cytoplasm, with inclusions similar to amylopectin granules, which are typically found in bradyzoites. An analysis of the cell death pathways in the parasite revealed that the compound caused a combination of apoptosis and autophagy. Fluorescence assays demonstrated that the redox environment in the LLC-MK2 cells becomes oxidant in the presence of the iron compound. Furthermore, a reduction in superoxide dismutase and catalase activities in the treated parasites and the presence of reactive oxygen species within the parasitophorous vacuoles were observed, indicating an impaired protozoan response against these radicals. These findings suggest that this compound disturbs the redox equilibrium of T. gondii, inducing cystogenesis and parasite death.

Risk factors, complications and survival after upper abdominal surgery: a prospective cohort study.

BACKGROUND: Preoperative weight loss and abnormal serum-albumin have traditionally been associated with reduced survival. More recently, a correlation between postoperative complications and reduced long-term survival has been reported and the significance of the relative proportion of skeletal muscle, visceral and subcutaneous adipose tissue has been examined with conflicting results. We investigated how preoperative body composition and major non-fatal complications related to overall survival and compared this to established predictors in a large cohort undergoing upper abdominal surgery. METHODS: From 2001 to 2006, 447 patients were included in a Norwegian multicenter randomized controlled trial in major upper abdominal surgery. Patients were now, six years later, analyzed as a single prospective cohort and overall survival was retrieved from the National Population Registry. Body composition indices were calculated from CT images taken within three months preoperatively. RESULTS: Preoperative serum-albumin <35 g/l (HR = 1.52, p = 0 .014) and weight loss >5 % (HR = 1.38, p = 0.023) were independently associated with reduced survival. There was no association between any of the preoperative body composition indices and reduced survival. Major postoperative complications were independently associated with reduced survival but only as long as patients who died within 90 days were included in the analysis. CONCLUSIONS: Our study has confirmed the robust significance of the traditional indicators, preoperative serum-albumin and weight loss. The body composition indices did not prove beneficial as global indicators of poor prognosis in upper abdominal surgery. We found no association between non-fatal postoperative complications and long-term survival.

[The subnuclei of the oculomotor nucleus in humans]. / Der Okulomotoriuskern und seine Subnuklei beim Menschen.

Examinations of eye movements offer an easy clinical method for the diagnosis of disturbances in the pathways for the generation of eye movements including the extraocular and inner eye muscles. A prerequisite is a good knowledge of the anatomy of the pathways for the generation of eye movements. The oculomotor nucleus represents an important relay station, which contains not only the motoneurons of four extraocular muscles and the levator palpebrae muscle, but also the preganglionic neurons of the ciliary ganglion for the mediation of the pupillary and accommodation response. Recent work about the special anatomy of the extraocular muscles and histochemical findings about the neurons in the Edinger-Westphal nucleus (EW), which indicated that this nucleus does not contain the preganglionic neurons of the ciliary ganglion, led to a new, modified map of the oculomotor nucleus complex. The most serious alteration refers to the location of the preganglionic neurons, which form a group of scattered neurons outside of the EW and now are termed EWpg. In contrast, the traditional cytoarchitectonically defined EW in the human eye contains peptidergic neurons with a completely different function, e.g., stress related, and is therefore termed EWcp (centrally projecting). A knowledge about the exact locations of extraocular motoneurons and preganglionic neurons is essential for the correct interpretation of clinico-anatomic findings.

Characterizing sleep disorders in an autism-specific collection of electronic health records.

OBJECTIVE/BACKGROUND: Sleep problems are common in people on the autism spectrum. This study reviews one detailed approach to querying the electronic health record (EHR) in a large tertiary care center. PATIENTS/METHODS: We developed methods for identifying people on the autism spectrum and defined their sleep problems using the key words, "sleep" or "melatonin", or International Classification of Diseases (ICD) codes. We examined treatment responses of these individuals to melatonin supplementation. RESULTS: Sleep problems were documented in 86% of patients with ages ranging from 6 to 30 years old. Our specific keyword search yielded more patients with sleep diagnoses than ICD codes alone. About two-thirds of patients who received melatonin supplementation reported benefit from its use. CONCLUSIONS: Our study provides a framework for using deidentified medical records to characterize sleep, a common co-occurring condition, in people on the autism spectrum. Using specific keywords could be helpful in future work that queries the EHR.

[Clinical effectiveness of home treatment as compared to inpatient treatment at the Alexianer Hospital Krefeld, Germany]. / Psychiatrische Akutbehandlung ohne Krankenhausbett-Klinische Wirksamkeit von "Home Treatment" am Beispiel der "Integrativen Psychiatrischen Behandlung (IPB)" am Alexianer-Krankenhaus Krefeld.

BACKGROUND: Although all relevant guidelines recommend "home treatment" (HT) as part of psychiatric care, this strategy is very rarely applied in the German mental health system. For the first time HT was introduced in Germany as "integrative psychiatric treatment" (IPT) at the Alexianer Hospital in Krefeld. In the present study IPT was compared for the first time with inpatient treatment considering patient characteristics, drop-out rates, effects on symptoms and rehopitalisation after treatment. METHOD: 106 patients who had been treated by IPT in 2001 (or subgroups) were compared to patients who were treated as inpatients in the same year (or subgroups). RESULTS: Regarding sample characteristics IPT patients were significantly older and more often female than inpatients. Inpatients were more frequently diagnosed with organic, schizophrenia or personality disorders. The drop-out rate from IPT (inpatient stay during IPT treatment) was 17.9 % (n = 19). The pre-post effect sizes on symptoms in 14 randomly selected patients with schizophrenia were very large (d = 1.7 - 2.6). At two-year follow-up there were no differences between IPT and a matched inpatient sample with respect to days spent in inpatient treatment (25.4 vs.27.9 days). CONCLUSION: In the German mental health system, at least in a subgroup of severely mentally ill patients, treatment effects of HT are comparable to the effects of inpatient treatment.

Randomized double-blind sham-controlled trial of thalamic versus GPi stimulation in patients with severe medically refractory Gilles de la Tourette syndrome.

BACKGROUND: There are still no sufficient data regarding the use of deep brain stimulation (DBS) in Gilles de la Tourette syndrome (GTS) and no agreement on optimal target. OBJECTIVE: To compare efficacy and safety of bilateral DBS of thalamus (centromedian-ventro-oral internus, CM-Voi) versus posteroventral lateral globus pallidus internus (pvl GPi)) versus sham stimulation, and baseline in severe medically refractory GTS. METHODS: In this randomized double-blind sham stimulation-controlled trial (RCT), 10 patients (3 women, mean age = 29.4 ± 10.2 SD, range 18-47) underwent three blinded periods each lasting three months including (i) sham, (ii) pvl GPi (on-GPi), and (iii) thalamic stimulation (on-thal) followed by an open uncontrolled long-term follow-up (up to 9 years) with individually determined target and stimulation settings. RESULTS: Nine patients completed the RCT. At group level, on-GPi - but not on-thal - resulted in a significant tic reduction compared to baseline, but had no effect on premonitory urges and psychiatric comorbidities. Direct comparisons of targets resulted in inconsistent or negative (compared to sham) findings. During follow-up, we found no improvement of tics, comorbidities, and quality of life at group level, however, single patients benefitted continuously from thalamic DBS. At last follow-up 89.9 months (mean) after surgery, 50% of patients had discontinued DBS. Hardware infections occurred in 3/10 patients. CONCLUSION: Our data suggest that the initial effect of pvl GPi DBS is superior to thalamic (CM-Voi) DBS. While half of the patients discontinued treatment, single patients benefitted from thalamic DBS even after years. It is likely that outcome is influenced by various factors beyond the mere change in tic severity.

Antitumoral synergism between a copper(II) complex and cisplatin improves in vitro and in vivo anticancer activity against melanoma, lung and breast cancer cells.

BACKGROUND: Intrinsic resistance of cancer cells is a major concern for the success of chemotherapy, and this undesirable feature stimulates further research into the design of new compounds and/or alternative multiple drug chemotherapy protocols. METHODS: In this study, we investigated the antitumoral potential of the coordination compounds [Cu(HPClNOL)Cl]Cl (1), [Fe(HPClNOL)Cl2]NO3(2) and [Mn(HPClNOL)Cl2] (3). Using the human, MCF-7 and A549, and the murine melanoma, B16-F10, cell lines, we determined the cytotoxicity, DCFH oxidation, disruption of mitochondrial membrane potential (ΔΨm), Sub-G1 and TUNEL positive cells, and caspase 8 and 9 activities. Fractional inhibitory concentration (FIC) and xenograft models were also assessed to evaluate the efficacy of antitumoral potential. RESULTS: We observed that only complex 1 was cytotoxic. The treatment of cancer cells with complex 1 triggered ROS generation and promoted the disruption of ΔΨm. Complex 1 increased the number of Sub-G1 and TUNEL positive cells, and the measurement of caspase 8 and 9 activity confirmed that apoptosis was triggered by the intrinsic pathway. FIC demonstrated that the combination of complex 1 with cisplatin was additive for the A549 cells whilst it was synergic for MCF-7 and B16-F10. Treatment with complex 1, either alone or combined with cisplatin, reduced tumor growth on xenograft models. CONCLUSIONS: The present study brings new clues regarding the mechanism of action of [Cu(HPClNOL)Cl]Cl, either alone or in combination with cisplatin. GENERAL SIGNIFICANCE: These results indicate that complex 1, administered either singly or in combination with current drugs, has real potential for use in cancer therapy.

Evaluating a simple method of neuroprotective hypothermia for newborn infants.

This study describes and evaluates a simple method of neuroprotective hypothermia for infants with hypoxic-ischaemic encephalopathy (HIE). Five term infants with HIE were cooled by applying soft, cold gel bags to the head. A radiant warmer, set to 34 degrees C, servo-controlled the temperature measured at a probe between the infant's back and the mattress. The infants' heads were shielded from the warmer. After 72 h, the infants were re-warmed by 0.2 degrees C per hour, by adjusting the radiant warmer. A rectal temperature of 34 degrees C was attained in a median time of 45 min. Mean rectal temperatures during cooling were 33.9 +/- 0.3 degrees C. There was good correlation between insulated back temperatures and deep rectal temperatures (r = 0.76). There were no major or irreversible adverse events during cooling. This method of cooling achieved rectal temperatures within the target range of 33-34 degrees C and re-warming was effective.

Curcumin-loaded nanoemulsion improves haemorrhagic stroke recovery in wistar rats.

Cerebrovascular diseases are currently a major global health problem. Considering the limitations of current therapy, the search for new alternatives for the treatment of these diseases is necessary and, in this context, curcumin, a molecule that has neuroprotective properties already described in the literature. A limiting factor when considering therapies for the nervous tissue is the presence of the blood-brain barrier which stimulates the search for new drug delivery strategies. In this context, nanoencapsulation seems to be a promising alternative. In this work, we compared the protective effects of free and nanoemulsified curcumin after intracerebral haemorrhage induced by collagenase (ICH) in Wistar rats. Injury area, motor activity, oxidative stress in the brain and serum biochemical parameters were investigated. Two hours after surgery, the first dose was injected intraperitoneally, followed by 24 and 48 h administration. Behavioural analysis was performed through 3 different tests: open field, beam walking and foot fault (24, 48 and 72 h respectively). At the end of the recovering time (3 days after injury), the animals were euthanized and the brain (for analysis of injury area and oxidative stress), blood (for biochemical parameters), kidney and liver (for histopathological examination) were investigated. Curcumin nanoemulsion 30 mg/kg was able to improve behavioural recovery, reduce the size of the haematoma and attenuate the weight loss caused by ICH. In terms of oxidative parameters, we observed that curcumin nanoemulsion modulated antioxidant responses with therapeutic potential against ICH. Only discrete results in few parameters were found with free-curcumin in the same dose.

Neuroimaging Advances in Deep Brain Stimulation: Review of Indications, Anatomy, and Brain Connectomics.

Deep brain stimulation is an established therapy for multiple brain disorders, with rapidly expanding potential indications. Neuroimaging has advanced the field of deep brain stimulation through improvements in delineation of anatomy, and, more recently, application of brain connectomics. Older lesion-derived, localizationist theories of these conditions have evolved to newer, network-based "circuitopathies," aided by the ability to directly assess these brain circuits in vivo through the use of advanced neuroimaging techniques, such as diffusion tractography and fMRI. In this review, we use a combination of ultra-high-field MR imaging and diffusion tractography to highlight relevant anatomy for the currently approved indications for deep brain stimulation in the United States: essential tremor, Parkinson disease, drug-resistant epilepsy, dystonia, and obsessive-compulsive disorder. We also review the literature regarding the use of fMRI and diffusion tractography in understanding the role of deep brain stimulation in these disorders, as well as their potential use in both surgical targeting and device programming.

Complex postglacial history of the temperate bark beetle Tomicus piniperda L. (Coleoptera, Scolytinae).

Tomicus piniperda is an economically important pine bark beetle infesting European Pinus spp. stands. We sequenced and analyzed 797 bp of the mitochondrial genome from individuals obtained from 34 populations sampled throughout the European range. We obtained 36 haplotypes, from which a haplotype network was constructed. In the Iberian Peninsula, high-genetic variability was detected with numerous endemic haplotypes. In contrast, the other European populations were less diverse with a single haplotype predominating from the Pyrenees to Scandinavia. Nevertheless, even within Europe, a few populations showed significant amounts of diversity. Four groups were obtained by Spatial Analysis of Molecular Variance, illustrating the regional characteristics of the species. T. piniperda had multiple fragmented refugia in the Iberian Peninsula. These currently isolated populations only partly contributed to postglacial re-colonizations of Northern Europe during interglacials. Nevertheless, few long-range migration events up to Northern Europe were detected, mostly originating from the Pyrenees. In the rest of Europe, the phylogeographical patterns were unclear, because of repeated cycles of contraction and expansion. The genetic analysis showed one glacial refugium in North-Central Europe, whereas other refugia most likely occurred in the Southern Alps, Apennine and the Balkans. The phylogeographical pattern depicted here reflects partly the postglacial history of the beetles' main host tree P. sylvestris.