An independent race model involving an abort and re-plan strategy explains reach redirecting movements during planning and execution

Abstract

Although race models have been extensively used to study inhibitory control, the mechanisms that enable the change of reach plans in the context of race models remain unexplored. We used a redirect task in which targets occasionally changed their locations, to study the control of reaching movements during movement planning and execution phases. We tested nine different race model architectures that could explain the redirect behaviour of reaching movements. We show that only the independent GO-STOP-GO model that reflects a plan-abort-re-plan strategy involving non-interacting elements, successfully explained the various behavioural measures such as the compensation function, and the pattern of error response reaction times. By extending the same race model to the execution phase, we could explain the extent and the pattern of hypometric trials. Interestingly, the race model also provided evidence that redirecting a movement during planning and execution shared the same inhibitory mechanism. Taken together, this study demonstrates the applicability of an independent race model to understand the computational mechanisms underlying the control of reach movements.

This article is protected by copyright. All rights reserved.

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AJR Reviewers: Thank You From the Editors and Staff

American Journal of Roentgenology, Volume 210, Issue 2, Page 237-238, February 2018.


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Additional Roles of Tomosynthesis in Breast Imaging–Guided Biopsies

American Journal of Roentgenology, Volume 210, Issue 2, Page W94-W94, February 2018.


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Medicolegal—Malpractice and Ethical Issues in Radiology

American Journal of Roentgenology, Volume 210, Issue 2, Page W92-W93, February 2018.


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Memorial—A. Everette James, Jr.

American Journal of Roentgenology, Volume 210, Issue 2, Page 466-466, February 2018.


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Section Editor's Notebook: Breast Cancer Screening—What Now, and What Next?

American Journal of Roentgenology, Volume 210, Issue 2, Page 239-240, February 2018.


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Lesions Without Borders: Scrotal Lesions That Involve Both the Intratesticular and Extratesticular Regions

American Journal of Roentgenology, Volume 210, Issue 2, Page W70-W79, February 2018.


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Androgen Therapy for Acute Myeloid and Hairy Cell Leukemia

Opinion statement

The purpose of this paper is to review the preclinical and clinical rationale for androgen therapy of acute myeloid (AML) and hairy cell leukemia (HCL). A major recent positive study should renew interest in this therapy, which has been reported to be effective in these leukemias for more than 50 years. Hopefully, renewed interest in this approach, which seems promising, will lead to well-designed modern studies that will precisely define a role for androgens in these leukemias. A recent large prospective, randomized study has demonstrated enhanced survival for elderly AML patients who present with WBC counts < 30,000/μL have improved overall survival when androgens are given post-remission, and numerous case reports suggest that androgens frequently restore normal peripheral blood counts in severely pancytopenic patients with HCL. Well-designed prospective studies are needed to precisely define which patients are most likely to benefit from androgen therapy and where in the treatment plan they should be incorporated.

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Leptomeningeal Metastases

Opinion statement

Treatment options for leptomeningeal metastases are expanding with greater tolerability and efficacy than in the past. Improved knowledge of molecular subtypes of some cancers can guide in choosing more effective therapeutic options; however, physicians should be mindful that these molecular types can be different in the central nervous system compared to the rest of the body. This is particularly true in breast and lung cancer, in which some patients now can live for many months or even years after diagnosis of leptomeningeal metastases. Options for intrathecal therapies are expanding, but physicians should be mindful that this is a passive delivery system that relies on normal CSF flow, so therapies will not penetrate bulky or parenchymal disease sites, especially in the presence of abnormal CSF flow. When chemotherapeutic options are lacking or unsuccessful, focal radiosurgery which can provide symptomatic relief and proton craniospinal radiation remain effective options. Hopefully more formal studies will be conducted in the future to verify which treatments are indeed most effective for particular types of cancer.

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Use of Next Generation Sequencing and Synergy Susceptibility Testing in Diagnosis and Treatment of Carbapenem-Resistant Klebsiella pneumoniae Blood Stream Infection

Early diagnosis and appropriate treatment for carbapenem-resistant Klebsiella pneumoniae (CR-Kp) infection is a big challenge for clinicians due to its high mortality. Every effort has been made to improve its clinical outcomes. However, treatment according to synergy susceptibility testing has never been reported in the literature. We reported a 29-year-old systemic lupus erythematosus female with CR-Kp blood stream infection. We highlighted the identification by next generation sequencing and treatment according to synergy susceptibility testing in the case.

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Premorbid Activity Limitation Stages Are Associated with Post-Hospitalization Discharge Disposition

AbstractObjectiveActivity of daily living (ADL) stages and instrumental activity of daily living (IADL) stage have demonstrated associations with mortality and health service utilization among older adults. This cohort study aims to assess the associations of premorbid activity limitation stages with acute hospital discharge disposition among community-dwelling older adults.DesignStudy participants were Medicare beneficiaries aged 65 years and older who enrolled in the Medicare Current Beneficiary Survey (MCBS) between 2001 and 2009. Associations of premorbid stages with discharge dispositions were estimated with multinomial logistic regression models adjusted for covariates.ResultsThe proportions of elderly Medicare patients discharged to home with self-care, home with services, post-acute care facilities, and other dispositions were 59%, 15%, 19%, and 7%, respectively. The adjusted relative risk ratios (RRR) and 95% confidence intervals of post-acute care facilities versus home with self-care discharge increased with higher premorbid activity limitation stages (except non-fitting stage III): 1.7 (1.5-2.0), 2.4 (2.0-2.9), 2.4 (1.9-3.0), and 2.5 (1.6-4.1) for ADL stages I-IV; a similar pattern was found for IADL stages. The adjusted RRRs of discharge to home with services also increased with higher premorbid activity limitation stages compared to no limitation.ConclusionsRoutinely assessed activity limitation stages predict post-hospitalization discharge disposition among older adults, and may be used to anticipate post-acute care and services utilization by elderly Medicare beneficiaries. Objective Activity of daily living (ADL) stages and instrumental activity of daily living (IADL) stage have demonstrated associations with mortality and health service utilization among older adults. This cohort study aims to assess the associations of premorbid activity limitation stages with acute hospital discharge disposition among community-dwelling older adults. Design Study participants were Medicare beneficiaries aged 65 years and older who enrolled in the Medicare Current Beneficiary Survey (MCBS) between 2001 and 2009. Associations of premorbid stages with discharge dispositions were estimated with multinomial logistic regression models adjusted for covariates. Results The proportions of elderly Medicare patients discharged to home with self-care, home with services, post-acute care facilities, and other dispositions were 59%, 15%, 19%, and 7%, respectively. The adjusted relative risk ratios (RRR) and 95% confidence intervals of post-acute care facilities versus home with self-care discharge increased with higher premorbid activity limitation stages (except non-fitting stage III): 1.7 (1.5-2.0), 2.4 (2.0-2.9), 2.4 (1.9-3.0), and 2.5 (1.6-4.1) for ADL stages I-IV; a similar pattern was found for IADL stages. The adjusted RRRs of discharge to home with services also increased with higher premorbid activity limitation stages compared to no limitation. Conclusions Routinely assessed activity limitation stages predict post-hospitalization discharge disposition among older adults, and may be used to anticipate post-acute care and services utilization by elderly Medicare beneficiaries. Corresponding author: Ling Na lingna2000@gmail.com; Disclosures: The research for this manuscript was supported by the grant from the National Institutes of Health (R01AG040105). There are no personal conflicts of interest of any of the authors, and no authors reported disclosures beyond the funding source. The opinions and conclusions of the authors are not necessarily those of the sponsoring agency. We certify that no party having a direct interest in the results of the research supporting this article has or will confer a benefit on us or on any organization with which we are associated. This material has not been previously presented at a meeting. Acknowledgement: We thank Dr. Margaret G. Stineman, MD for her contribution in conceptualization of the study. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Effects of cane use and position on performance of the sit-to-stand task in stroke patients

ABSTRACTObjectiveTo examine the effect of cane use and cane positions on the sit-to-stand (STS) performance of stroke patients.DesignIn a crossover study, 30 stroke patients performed STS test in seven situations in a random sequence: without a cane, three positions with a regular cane (parallel to the ankle, parallel to the 5th toe, and 10 cm in front of the 5th toe), and the same three positions with a quad cane. The peak vertical ground reaction force (GRF) and maximum vertical cane support force during STS were recorded.ResultsUsing a cane significantly reduced the peak GRF by 3%~9% of body weight compared to that without a cane (p=0.000~0.023). Different cane positions strongly influenced the maximum cane support force and peak GRF. When the cane was closer to the ankle, the maximal cane support force increased by 6.7%~8.6% of body weight, which resulted in a decrease in the peak GRF.ConclusionsBoth types of cane reduced lower extremities' load during STS. When the cane was closer to the trunk, the load on legs was lessened, while the load on the upper extremity increased. Upper extremity's load during STS was greater when using quad cane than using regular cane. Objective To examine the effect of cane use and cane positions on the sit-to-stand (STS) performance of stroke patients. Design In a crossover study, 30 stroke patients performed STS test in seven situations in a random sequence: without a cane, three positions with a regular cane (parallel to the ankle, parallel to the 5th toe, and 10 cm in front of the 5th toe), and the same three positions with a quad cane. The peak vertical ground reaction force (GRF) and maximum vertical cane support force during STS were recorded. Results Using a cane significantly reduced the peak GRF by 3%~9% of body weight compared to that without a cane (p=0.000~0.023). Different cane positions strongly influenced the maximum cane support force and peak GRF. When the cane was closer to the ankle, the maximal cane support force increased by 6.7%~8.6% of body weight, which resulted in a decrease in the peak GRF. Conclusions Both types of cane reduced lower extremities' load during STS. When the cane was closer to the trunk, the load on legs was lessened, while the load on the upper extremity increased. Upper extremity's load during STS was greater when using quad cane than using regular cane. Correspondence to: Dr. Mau-Roung Lin, Institute of Injury Prevention and Control, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11031, Taiwan, R.O.C., Phone: 886-2-27398755; Fax: 886-2-27398755; E-mail: mrlin@tmu.edu.tw Financial support: This work was funded by the National Health Research Institute (NHRI-EX100-9805PI) and the Ministry of Technology and Science (MOST106-2314-B-038-046), Taiwan. No commercial party having a direct or indirect interest in the subject matter of this research has or will confer a benefit upon the authors or upon any organization with which the authors are associated. Conflicts of interest: The authors have no conflicts of interest to declare. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Regarding “Lethal hypothermia – a sometimes elusive diagnosis”

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Utility of Pathology Imagebase for Standardization of Prostate Cancer Grading

Abstract

Aims

Despite efforts to standardize grading of prostate cancer, there is still a considerable variation in grading practices even among experts. In this study we describe the use of Pathology Imagebase, a novel reference image library, for setting an international standard in prostate cancer grading.

Methods and Results

The International Society of Urological Pathology (ISUP) recently launched a reference image database supervised by experts. A panel of 24 international experts in prostate pathology independently reviewed microphotographs of 90 cases of prostate needle biopsies with cancer. A linear weighted kappa of 0.67 (95% confidence interval 0.62 - 0.72) and consensus was reached in 50 cases. The inter-observer weighted kappa varied from 0.48 to 0.89. The highest level of agreement was seen for Gleason score (GS) 3+3=6 (ISUP grade 1), while higher grades and particularly GS 4+3=7 (ISUP grade 3) showed considerable disagreement. Once a 2/3 majority was reached, images were automatically moved into a public database available for all ISUP members at www.isupweb.org. Non-members are able to access a limited number of cases.

Conclusions

It is anticipated that the database will assist pathologists to calibrate their grading and, hence, decrease inter-observer variability. It will also help identify instances where definitions of grades need to be clarified.

This article is protected by copyright. All rights reserved.

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Fine-needle aspiration of a pancreatic neuroendocrine tumor with prominent rhabdoid features

Pancreatic neuroendocrine tumors (PanNETs) are uncommon neoplasms that conventionally possess architectural and cytomorphological features seen in neuroendocrine neoplasms found at other sites. When present, these features often allow rapid identification of neuroendocrine differentiation and an accurate diagnosis. Here, we report the cytologic findings seen on fine-needle aspiration (FNA) of a PanNET with distinct rhabdoid features. This morphology is rare in PanNETs and has been reported in only two case series examining surgical resection specimens and has not been described on FNA. It is important to recognize this morphology as this variant appears to portend an aggressive clinical course. Furthermore, unfamiliarity with this morphologic variant may lead to a larger initial differential and thus delay final diagnosis.

http://ift.tt/2Dz2Ckp

Role of Chemotherapy in the Neoadjuvant/Adjuvant Setting for Patients With Rectal Adenocarcinoma Undergoing Chemoradiotherapy and Surgery or Radiotherapy and Surgery

Abstract

Rectal cancer has been successfully managed in the last couple of decades. In the USA, as the initial approach, neoadjuvant concurrent chemoradiation has been associated not only with decrease in tumor size and recurrence but also with higher resection rate with minimal side effects. Data support that addition of chemotherapy to radiotherapy is superior to radiotherapy alone in the neoadjuvant setting. Recent debates have addressed the question of administration of adjuvant chemotherapy following surgery. In this article, we discuss the role of chemotherapy in both the neoadjuvant and the adjuvant settings for locally advanced rectal cancer.

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Pediatric multi-drug resistant-tuberculosis and HIV co-infection in a resource—limited setting: a case report

Tuberculosis remains a major cause of morbidity and mortality worldwide, especially in developing countries. The diagnosis and treatment of multi-drug resistant tuberculosis (MDR-TB) in children remain a major...

http://ift.tt/2BlCeW1

Contrasting development of lysigenous aerenchyma in two rice genotypes under phosphorus deficiency

Phosphorus (P) deficiency is a major limitation to plant growth. Under several abiotic stresses, including P deficiency, upland cereal crops, such as maize, are well known to develop lysigenous aerenchyma, a r...

http://ift.tt/2n35NHi

Screening of methicillin-resistant Staphylococcus aureus nasal colonization among elective surgery patients in referral hospital in Indonesia

Methicillin-resistant Staphylococcus aureus (MRSA) colonization is associated with serious surgical site infection in high-risk patients. High prevalence of MRSA colonization was reported in many settings, noneth...

http://ift.tt/2BnWrdS

Establishment of hematological reference intervals for healthy adults in Asmara

Clinical laboratory reference intervals used in a specific area should be derived from the local population as they are influenced by many factors. The purpose of this quantitative cross sectional study was to...

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Minimum values for midluteal plasma progesterone and estradiol concentrations in patients who achieved pregnancy with timed intercourse or intrauterine insemination without a human menopausal gonadotropin

The aim of the study was to assess the lower limits of midluteal plasma progesterone and estradiol concentrations in patients who achieved pregnancy with timed intercourse or intrauterine insemination without ...

http://ift.tt/2BlC7tz

Incidence of neuromyelitis optica spectrum disorder in the Central Denmark Region

Objectives

Neuromyelitis optica (NMO)/NMO spectrum disorder (NMOSD) may be misdiagnosed as multiple sclerosis. The aim of this study was to (i) to measure AQP4-IgG in patients who fulfilled the clinical and radiological criteria of NMOSD in the Central Denmark Region and (ii) to estimate the incidence of NMOSD in the region, according to both the 2006 Wingerchuk criteria and the 2015 International Panel for NMO Diagnosis criteria.

Materials and methods

Medical records of all patients diagnosed with a demyelinating disorder in the region from 1 January 2012 to 31 December 2013 were reviewed. Patients were classified as having (i) "NMO" if the 2006 criteria were met, (ii) "NMOSD with AQP4-IgG" or (iii) "NMOSD without/unknown AQP-IgG" if the new 2015 NMOSD criteria were met. Patients with core symptoms were invited to provide a blood sample for AQP4-IgG analysis with an enzyme-linked immunosorbent assay and a cell-based indirect immunofluorescence assay.

Results

In 191 patients with core symptoms, one met the 2015 NMOSD with AQP4-IgG criteria. Two patients met the 2006 NMO and 2015 NMOSD without/unknown AQP4-IgG criteria. Among 108 patients providing a blood sample, all were seronegative. The estimated incidence of NMO (2006 criteria) and NMOSD (2015 criteria) was 0.08 and 0.12 per 100 000 person-years, respectively.

Conclusion

NMO/NMOSD is a rare disease in the Central Denmark Region, with a considerably lower incidence rate than previously estimated in a neighbouring region.

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Guillain-Barre syndrome caused by hepatitis E infection: case report and literature review

Hepatitis E infection is a global disorder that causes substantial morbidity. Numerous neurologic illnesses, including Guillain–Barre syndrome (GBS), have occurred in patients with hepatitis E virus (HEV) infe...

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Systematic review with meta-analysis: de novo non-alcoholic fatty liver disease in liver-transplanted patients

Summary

Background

De novo non-alcoholic fatty liver disease (NAFLD) in liver-transplanted patients for cirrhosis not due to non-alcoholic steatohepatitis (NASH) is becoming a growing phenomenon.

Aims

We performed a systematic review and evaluated the prevalence of this event and possible associated factors.

Methods

A literature search in medical databases (PubMed, MEDLINE/OVIDSP, Science Direct and EMBASE) was performed in March 2017. Relevant publications were identified in most important databases. We estimated the pooled prevalence of NAFLD and NASH in patients with liver transplant. The data have been expressed as proportions/percentages, and 95% confidence intervals (CI) were calculated, using the inverse variance method. Odd ratios (OR) and 95% confidence intervals (95% CI) were estimated.

Results

Twelve studies were selected, enrolling 2166 subjects overall undergoing post-liver transplant biopsy. The pooled weighted prevalence of de novo NAFLD was 26% (95% CI 20%-31%). The pooled weighted prevalence of NASH was 2% (95% CI 0%-3%). The highest prevalences of de novo NAFLD were found for patients transplanted for alcoholic cirrhosis (37%) and cryptogenic cirrhosis (35%) and for patients taking tacrolimus (26%). Tacrolimus showed a risk of NAFLD similar to ciclosporin (OR = 1.02, 95% CI 0.3-3.51).

Conclusions

Patients undergoing liver transplant are more prone to experience diabetes, hypertension or dyslipidaemia, and NAFLD may be an important element in this context. In this study, we show how the prevalence of NASH tends to remain significant and similar to the general population. Moreover, this study suggests a possible association with specific transplant indications. Further studies are required to confirm these findings.

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Use of olmesartan and enteropathy outcomes: a multi-database study

Summary

Background

Multiple case reports suggest that olmesartan may be linked to sprue-like enteropathy; however, few epidemiological studies have examined this association and results have been mixed.

Aim

To assess whether olmesartan is associated with a higher rate of enteropathy vs other angiotensin II receptor blockers (ARBs).

Methods

We conducted a cohort study among ARB initiators in 5 US claims databases representing different health insurance programmes. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for enteropathy-related outcomes, including coeliac disease, malabsorption, concomitant diagnoses of diarrhoea and weight loss, and non-infectious enteropathy, comparing olmesartan initiators to initiators of other ARBs after propensity score (PS) matching.

Results

We identified 1 928 469 eligible patients. The unadjusted incidence rates were 0.82, 1.41, 1.66 and 29.20 per 1000 person-years for coeliac disease, malabsorption, concomitant diagnoses of diarrhoea and weight loss, and non-infectious enteropathy respectively. HRs after PS matching comparing olmesartan to other ARBs were 1.21 (95% CI, 1.05-1.40), 1.00 (95% CI, 0.88-1.13), 1.22 (95% CI, 1.10-1.36) and 1.04 (95% CI, 1.01-1.07) for each outcome. HRs were larger for patients aged 65 years and older (eg for coeliac disease, 1.57 [95% CI, 1.20-2.05]), for patients receiving treatment for more than 1 year (1.62 [95% CI, 1.24-2.12]), and for patients receiving higher cumulative olmesartan doses (1.78 [95% CI, 1.33-2.37]).

Conclusions

This large-scale, multi-database study found a higher rate of enteropathy in olmesartan initiators as compared to initiators of other ARBs, although the absolute incidence rate was low in both groups.

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Predicting corticosteroid-free endoscopic remission with vedolizumab in ulcerative colitis

Summary

Background

Vedolizumab is an effective therapy for ulcerative colitis (UC), but costly and slow to work. New clinical responses occur after 30 weeks of therapy.

Aims

To enable physicians, patients, and insurers to predict whether a patient with UC will respond to vedolizumab at an early time point after starting therapy.

Methods

The clinical study data request website provided the phase 3 clinical trial data for vedolizumab. Random forest models were trained on 70% and tested on 30% of the data to predict corticosteroid-free endoscopic remission at week 52. Models were constructed using baseline data, or data through week 6 of vedolizumab therapy from 491 subjects.

Results

The AuROC for prediction of corticosteroid-free endoscopic remission at week 52 using baseline data was only 0.62 (95% CI: 0.53-0.72), but was 0.73 (95% CI: 0.65-0.82) when using data through week 6. A total of 47% of subjects were predicted to be remitters, and 59% of these subjects achieved corticosteroid-free endoscopic remission, in contrast to 21% of the predicted non-remitters. A week 6 prediction using FCP ≤234 μg/g was nearly as accurate.

Conclusions

A machine learning algorithm using laboratory data through week 6 of vedolizumab therapy was able to accurately identify which UC patients would achieve corticosteroid-free endoscopic remission on vedolizumab at week 52. Application of this algorithm could have significant implications for clinical decisions on whom to continue on this costly medication when the benefits of the vedolizumab are not clinically apparent in the first 6 weeks of therapy.

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Review article: long-term safety of oral anti-viral treatment for chronic hepatitis B

Summary

Background

Safety profile of nucleos(t)ide analogues is an important issue in view of its widespread use for decades in patients with chronic hepatitis B (CHB).

Aim

To review and evaluate the latest evidence on the safety profiles of the six approved nucleoside analogues.

Methods

Relevant articles related to nucleoside analogue safety were selected for review following extensive language- and date-unrestricted, electronic searches of the literature.

Results

Nephrotoxicity has been well reported in patients received older generations of nucleotide analogues, namely adefovir dipivoxil and tenofovir disoproxil fumarate (TDF). Yet risks of renal failure and renal replacement therapy were similar in patients treated with nucleoside analogues versus nucleotide analogues in real-life setting. Bone toxicity is closely related to nucleoside analogue effect on renal proximal tubular and phosphaturia. Real-life data demonstrated increased risk of hip fracture in patients received adefovir but not TDF. The newly approved tenofovir alafenamide (TAF) has improved renal and bone safety profiles compared to TDF. Long-term use of nucleoside analogues eg entecavir does not increase the risk of other cancers. Muscular toxicity may be seen in telbivudine-treated patients so regular monitoring is advised. Peripheral neuropathy and lactic acidosis are rare adverse events. Latest international guidelines support the use of TDF, telbivudine and lamivudine during pregnancy; breastfeeding is not contraindicated during TDF therapy.

Conclusions

Long-term safety profile of nucleoside analogues is now better defined with more data from large real-life cohorts and clinical trials with long-term follow-up. The new nucleotide analogue, TAF is now available with favourable renal and bone safety profiles.

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Delivery of Adeno-Associated Virus Vectors in Adult Mammalian Inner-Ear Cell Subtypes Without Auditory Dysfunction

Human Gene Therapy , Vol. 0, No. 0.


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ASSESSMENT OF MECHANICAL PROPERTIES OF HUMAN HEAD TISSUES FOR TRAUMA MODELLING

Abstract

Many discrepancies are found in the literature regarding the damage and constitutive models for head tissues as well as the values of the constants involved in the constitutive equations. Their proper definition is required for consistent numerical model performance when predicting human head behaviour, and hence skull fracture and brain damage. The objective of this research is to perform a critical review of constitutive models and damage indicators describing human head tissues response under impact loading. A 3D finite element human head model has been generated using computed tomography images, which has been validated through the comparison to experimental data in the literature. The threshold values of the skull and the scalp that lead to fracture have been analysed. We conclude that: 1) compact bone properties are critical in skull fracture, 2) the elastic constants of the cerebrospinal fluid affect the intracranial pressure distribution, and 3) the consideration of brain tissue as a nearly-incompressible solid with a high (but not complete) water content offers pressure responses consistent with the experimental data.

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Peer Toy Play as a Gateway to Children’s Gender Flexibility: The Effect of (Counter)Stereotypic Portrayals of Peers in Children’s Magazines

Abstract

Extensive evidence has documented the gender stereotypic content of children's media, and media is recognized as an important socializing agent for young children. Yet, the precise impact of children's media on the endorsement of gender-typed attitudes and behaviors has received less scholarly attention. We investigated the impact of stereotypic and counter-stereotypic peers pictured in children's magazines on children's gender flexibility around toy play and preferences, playmate choice, and social exclusion behavior (n = 82, age 4–7 years-old). British children were randomly assigned to view a picture of a peer-age boy and girl in a magazine playing with either a gender stereotypic or counter-stereotypic toy. In the stereotypic condition, the pictured girl was shown with a toy pony and the pictured boy was shown with a toy car; these toys were reversed in the counter-stereotypic condition. Results revealed significantly greater gender flexibility around toy play and playmate choices among children in the counter-stereotypic condition compared to the stereotypic condition, and boys in the stereotypic condition were more accepting of gender-based exclusion than were girls. However, there was no difference in children's own toy preferences between the stereotypic and counter-stereotypic condition, with children preferring more gender-typed toys overall. Implications of the findings for media, education, and parenting practices are discussed, and the potential for counter-stereotypic media portrayals of toy play to shape the gender socialization of young children is explored.

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Acute-onset Restless legs syndrome in acute neurological conditions—a prospective study on patients with the Guillain-Barre syndrome and acute stroke

Objectives

While the Restless legs syndrome (RLS) is usually recognized as a chronic condition, it has often been diagnosed among patients with acute neurological illnesses, in which limb discomfort is reported. This study was conducted to determine how many among these, actually have acute-onset RLS, and also to evaluate characteristics of this subgroup of patients with Guillain-Barre syndrome (GBS) and stroke developing acute-onset RLS.

Methods

Consecutive patients diagnosed with GBS and eligible stroke patients, admitted to our Neurology services over a 1-year period, were enrolled. They were evaluated for symptoms of RLS based on IRLSSG consensus criteria and the AIIMS RLS Questionnaire for Indian patients (ARQIP).

Results

Forty adults with GBS and 58 with stroke were included. A total of 10 of the 40 (25%) patients with GBS developed definite acute RLS, which was mostly monophasic. Seven (70%) of these had demyelinating type of GBS, a significant association with acute RLS (P = .024). Six of the 58 stroke patients (10%) developed definite acute-onset, often persistent RLS. Subcortical location showed significant association with increased risk of developing acute RLS (P < .001). All patients diagnosed with acute-onset RLS had an immediate and good response to dopamine agonists.

Conclusion

This is the first study showing that acute-onset RLS is common, affecting nearly 25% of patients with GBS and 10% patients with acute stroke. Recognizing and treating it can majorly contribute toward symptom relief and early improvement in the quality of life for this population.

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Drug resistant tuberculosis in Saudi Arabia: an analysis of surveillance data 2014–2015

There is limited data that investigates the national rates of drug-resistant tuberculosis (TB) in Saudi Arabia.

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The efficacy of ampicillin compared with ceftriaxone on preventing cesarean surgical site infections: an observational prospective cohort study

Cesarean surgical site infections (SSIs) can be prevented by proper preoperative antibiotic prophylaxis. Differences in antibiotic selection in clinical practice exist according to obstetricians' preferences d...

http://ift.tt/2rwTjfN

Higher third-generation cephalosporin prescription proportion is associated with lower probability of reducing carbapenem use: a nationwide retrospective study

The ongoing extended spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) pandemic has led to an increasing carbapenem use, requiring release of guidelines for carbapenem usage in France in late 2010. We s...

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Antimicrobial effect of copper alloys on Acinetobacter species isolated from infections and hospital environment

An increased proportion of Gram-negative bacteria have recently been reported among etiologic agents of infection. In Poland, Acinetobacter baumannii is a big problem for hospitals, especially intensive care unit...

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Multi-drug resistant Acinetobacter species: a seven-year experience from a tertiary care center in Lebanon

Acinetobacter species have become increasingly common in the intensive care units (ICU) over the past two decades, causing serious infections. At the American University of Beirut Medical Center, the incidence of...

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Study on the persistence of Zika virus (ZIKV) in body fluids of patients with ZIKV infection in Brazil

Zika virus (ZIKV) has been identified in several body fluids of infected individuals. In most cases, it remained detected in blood from few days to 1 week after the onset of symptoms, and can persist longer in ur...

http://ift.tt/2n5qD86

Systematic review: psychosocial factors associated with pain in inflammatory bowel disease

Summary

Background

Pain is a frequently reported symptom of inflammatory bowel disease (IBD) experienced by patients in active disease and remission. Psychological factors play a significant role in pain, but have not been systematically reviewed in IBD.

Aim

To review psychosocial factors associated with pain in adults diagnosed with IBD.

Methods

Electronic (PsycInfo, MEDLINE, EMBASE, Cochrane Library, CINAHL, Web of Science), and hand-searching were conducted February-May 2017. Two authors carried out screening and data extraction.

Results

Fifteen studies including 5539 IBD patients were identified. Emotional, cognitive-behavioural and personality factors were associated with IBD-pain. Depression and anxiety were the most commonly explored constructs, followed by perceived stress and pain catastrophising, all of which were positively associated with greater pain. Greater abdominal pain was associated with a concurrent mood disorder over fivefold (OR 5.76, 95% CI 1.39, 23.89). Coping strategies and pain fear avoidance correlated with pain levels. Perceived social support (r = .26) and internal locus of control (r = .33) correlated with less pain. Patients reporting pain in IBD remission more frequently had an existing diagnosis of a mood disorder, a chronic pain disorder and irritable bowel syndrome. Six studies controlled for disease activity, of which 4 found that psychosocial factors significantly predicted pain. The majority of studies (n = 10) were of high quality.

Conclusion

Psychosocial factors appear to play a significant role in IBD-pain. Further research is required to explore psychosocial constructs in relation to IBD-pain, with use of validated pain measures, large sample sizes and clearer characterisation of disease activity.

http://ift.tt/2DsM9uw

Comparison between a nurse-led weaning protocol and weaning based on physician’s clinical judgment in tracheostomized critically ill patients: a pilot randomized controlled clinical trial

Weaning protocols expedite extubation in mechanically ventilated patients, yet the literature investigating the application in tracheostomized patients remains scarce. The primary objective of this parallel ra...

http://ift.tt/2F2CWte

The Expanding World of N-MYC-Driven Tumors [Reviews]

Enhanced and deregulated expression of N-MYC, a member of the MYC family of transcription factors, drives the development of multiple tumors, including tumors of the nervous and hematologic systems and neuroendocrine tumors in other organs. This review summarizes the cell-of-origin, biological features, associated signaling pathways, and current treatment strategies for N-MYC–driven tumors. We also highlight biological differences within specific tumor types that are driven by the different MYC proteins.

Significance: N-MYC is a driver of multiple tumor types that are derived through a mechanism that involves direct differentiation within the same lineage (e.g., in the case of neuroblastoma, medulloblastoma, and acute myeloid leukemia) and is often associated with a poor prognosis. Emerging data suggest that N-MYC also drives other tumor types through a mechanism that promotes a lineage switch and that this switch may be exploited for therapeutic purposes. Cancer Discov; 8(2); 1–14. ©2018 AACR.

http://ift.tt/2DZKCgx

Improving Genomic Prediction in Cassava Field Experiments by Accounting for Inter-plot Competition

Plants' competing for available resources is an unavoidable phenomenon in a field. We conducted studies in cassava (Manihot esculenta Crantz) in order to understand the pattern of this competition. Taking into account the competitive ability of genotypes while selecting parents for breeding advancement or commercialization can be very useful. We assumed that competition could occur in two levels i) at the genotypic level, which we called as inter-clonal, and ii) at the plot level irrespective of the type of genotype, which we call as inter-plot competition or competition error. Modification in incidence matrices was applied in order to relate neighboring genotype/plot to the performance of a target genotype/plot with respect to its competitive ability. This was added into a genomic selection model to simultaneously predict the direct and competitive ability of a genotype. Predictability of the models was tested through a 10-fold cross-validation method repeated five times. The best model was chosen as the one with the lowest prediction root mean squared error (pRMSE) compared to that of the base model having no competitive component. Results from our real data studies indicated that less than 10% increase in accuracy was achieved with GS-inter-clonal competition model but this value reached up to 25% with a GS-competition error model. We also found that the competitive influence of a cassava clone is not just limited to the adjacent neighbors but spreads beyond them. Through simulations we found that a 26% increase of accuracy in estimating trait genotypic effect can be achieved even in the presence of high competitive variance.

http://ift.tt/2DE4Grh

An Overexpressed Q Allele Leads to Increased Spike Density and Improved Processing Quality in Common Wheat (Triticum aestivum)

Spike density and processing quality are important traits in the modern wheat production that is controlled by multiple gene loci. The associated genes have been intensively studied and new discoveries have been constantly reported during the past few decades. However, no gene playing significant roles in the development of these two traits was identified. In the current study, a common wheat mutant with extremely compact spikes and good processing quality was isolated and characterized. A new allele (Q^c1) of Q gene (an important domestication gene) responsible for the mutant phenotype was cloned and the molecular mechanism for the mutant phenotype was studied. Results revealed that Q^c1 was originated from a point mutation that interferes with the miRNA172-directed cleavage of the Q transcripts, leading to its overexpression. It also reduces the longitudinal cell size of rachises, resulting in an increased spike density. Furthermore, Q^c1 increases the number of vascular bundles, which suggests a higher efficiency in the transportation of assimilates in the spikes of the mutant than that of WT. This accounts for the improved processing quality. The effects of Q^c1 on spike density and wheat processing quality were confirmed by analyzing nine common wheat mutants possessing four different Q^c alleles. These results deepen our understanding of the key roles of Q gene and provide new insights for the potential application of Q^c alleles in wheat quality breeding.

http://ift.tt/2n1dUV0

Shaping substrate selectivity in a broad spectrum metallo-{beta}-lactamase [PublishAheadOfPrint]

Metallo-β-lactamases (MBLs) are the major group of carbapenemases produced by bacterial pathogens. The design of MBL inhibitors has been limited, among other issues, by the incomplete knowledge about how these enzymes modulate substrate recognition. While most MBLs are broad-spectrum enzymes, B2 MBLs are exclusive carbapenemases. This narrower substrate profile has been attributed to a sequence insertion present in B2 enzymes that limits the accessibility to the active site. In this work, we evaluate the role of sequence insertions naturally occurring in the B2 enzyme Sfh-I and in the broad-spectrum B1 enzyme SPM-1. We engineered a chimeric protein in which the sequence insertion of SPM-1 was replaced by the one present in Sfh-I. The chimeric variant is a selective cephalosporinase, revealing that the substrate profile of MBLs can be further tuned depending on the protein context. These results also show that the stable scaffold of MBLs allows a modular engineering much richer than the one observed in nature.

http://ift.tt/2DWEsOh

Unravelling the metabolic routes of retapamulin: insights into drug development of pleuromutilins [PublishAheadOfPrint]

Retapamulin, a semi-synthetic pleuromutilin derivative, is exclusively used for the topical short-term medication of impetigo and staphylococcal infections. In the present study, we report that retapamulin is adequately and rapidly metabolized in vitro via various metabolic pathways such as hydroxylation, including mono-, di- and tri-hydroxylation and demethylation. Like tiamulin and valnemulin, the major metabolic routes of retapamulin were hydroxylation at the 2β and 8α positions of the mutilin moiety. Moreover, in vivo metabolism concurred with the results of the in vitro assays. Additionally, we observed the significant inter-species metabolic differences of retapamulin. Until now, modifying the side chain was the mainstream for new drug discovery of the pleuromutilins. This approach, however, could not resolve the low bioavailability and short efficacy of the drugs. Considering the rapid metabolism of the pleuromutilins mediated by cytochrome P450 enzymes, we propose that blocking the active metabolic site (C-2 and C-8 motif) or administering the drug in combination with cytochrome P450 enzymes inhibitor to be promising pathways in the development of novel pleuromutilins drugs with slow metabolism and long efficacy.

http://ift.tt/2DsiW37

Cellular pharmacokinetics and intracellular activity of gepotidacin against Staphylococcus aureus with different resistance phenotypes in models of cultured phagocytic cells. [PublishAheadOfPrint]

Gepotidacin (GSK2140944), a novel triazaacenaphthylene bacterial topoisomerase inhibitor, is currently in clinical development for the treatment of bacterial infections. This study examines in vitro its activity against intracellular Staphylococcus aureus (involved in the persistent character of skin and skin structure infections) using a pharmacodynamic model and in relation to cellular pharmacokinetics in phagocytic cells. Compared to oxacillin, vancomycin, linezolid, daptomycin, azithromycin, and moxifloxacin, gepotidacin was (i) more potent intracellularly (C_s [apparent bacteriostatic effect] reached at an extracellular concentration of about 0.7 x its MIC and not affected by resistance mechanisms to the comparators) and (ii) caused a maximal reduction of the intracellular burden (E_max) of about -1.6 log₁₀ CFU (better than linezolid, macrolides, and daptomycin; similar to moxifloxacin). After 24 h of incubation of infected cells with antibiotics at 100 X their MIC, the intracellular persisting fraction was < 0.1 % with moxifloxacin, 0.5 % with gepotidacin and > 1 % with other drugs. Accumulation and efflux of gepotidacin in phagocytes was very fast (k_in and k_out ~0.3 min^-1; plateau reached within 15 minutes) but modest (intracellular to extracellular concentration ratio ~1.6). In cell fractionation studies, about 40-60 % of the drug was recovered in the soluble fraction and ~40% associated with lysosomes in uninfected cells. In infected cells, about 20% of cell-associated gepotidacin was recovered in a sedimentable fraction that also contained bacteria. This study highlights the potential for further study of gepotidacin to fight infections where intracellular niches may play a determining role in bacterial persistence and relapses.

http://ift.tt/2DWEmWV

Population Pharmacokinetic Model for Cefuroxime Used in Coronary Artery Bypass Graft Surgery with Cardiopulmonary Bypass: Model-Based Evaluation of Standard Dosing Regimens [PublishAheadOfPrint]

The purpose of this study was to investigate the population PK of cefuroxime in patients undergoing coronary artery bypass graft (CABG) surgery. In this observational pharmacokinetic study, multiple blood samples were collected over a 48-h interval of intravenous cefuroxime administration. The samples were analyzed by using a validated high-performance liquid chromatography (HPLC) method. Population pharmacokinetic models were developed using Monolix 4.4 software. Pharmacokinetic-pharmacodynamic (PK-PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets. A total of 468 blood samples were analyzed from 78 patients. The PK for cefuroxime was best described by a two-compartment model with between-subject variability on clearance, volume of the central compartment, and volume of the peripheral compartment. Clearance of cefuroxime was related to creatinine clearance (CL_CR). Dosing simulations showed that standard dosing regimens of 1.5 g could achieve the PK-PD target of 65% fT_>MIC for an MIC of 8 mg/L in patients with CL_CR of 30, 60, 90 ml/min, whereas this dosing regimens failed to achieve the PK-PD target in patients with CL_CR of ≥125 ml/min. In conclusion, administration of standard doses of 1.5 g three times daily provided adequate antibiotic prophylaxis in patients undergoing CABG surgery. Lower doses failed to achieve the PK-PD target. Patients with high CL_CR values are required either higher doses or shorter intervals of cefuroxime dosing. On the other hand, lower doses (1 g three times daily) produced adequate target attainment for patients with low CLCR (≤30 ml/min).

http://ift.tt/2DrbFAC

Population pharmacokinetics of high-dose tigecycline in patients with sepsis or septic shock [PublishAheadOfPrint]

Background and objective: Tigecycline is a glycylcycline often used in critically ill patients as antibiotic of last resort. The pharmacokinetics (PK) of tigecycline in Intensive Care Unit (ICU) patients can be affected by severe pathophysiological changes so that standard dosing might not be adequate. The aim of this study was to describe population PK of high dose tigecycline in patients with sepsis or septic shock and evaluate relationship between individual PK parameters and patient's covariates.

Materials and Methods: The study population consisted of 37 adult ICU patients receiving 200 mg loading dose of tigecycline followed by multiple doses of 100 mg every 12 h. Blood samples were collected at 0.5, 2, 4, 8 and 12 h after dose administration. Two-compartment model with inter-individual (IIV) and inter-occasion (IOV) variability in PK parameters was used to describe the concentration-time course of tigecycline.

Results: The estimated values of mean population PK parameters were 22.1 L/h and 69.4 L/h for elimination and inter-compartmental clearance, 162 L and 87.9 L for volume of central and peripheral compartment. The IIV and IOV in clearance was lower than 20%. The estimated values of distribution volumes were different than previously published values, which might be due to pathophysiological changes in ICU patients. No systematic relationship between individual PK parameters and patient's covariates was found.

Conclusions: The developed model does not show evidence that individual tigecycline dosing adjustment based on patient's covariates is necessary to obtain the same target concentration in patients with sepsis or septic shock. Dosing adjustments should be based on the pathogens, their susceptibility and PK targets.

http://ift.tt/2E1C3SL

Amikacin Pharmacokinetic-Pharmacodynamic (PK-PD) Analysis in Pediatric Cancer Patients [PublishAheadOfPrint]

We performed PK-PD and simulation analyses to evaluate standard 15 mg/kg/day amikacin in children with cancer and to determine an optimal dosing strategy. A population pharmacokinetic model was developed from clinical data collected in 34 pediatric patients and used in a simulation study to predict the population probability of various dosing regimens to achieve accepted safety- (fC_min < 10 mg/L) and efficacy-linked (fC_max/MIC ≥ 8) targets. In addition, an adaptive resistance PD (ARPD) model of Pseudomonas aeruginosa was built based on literature time-kill curve data and linked to the PK model to perform PK-ARPD simulations and compare results with the probability approach. Using the probability approach, an amikacin dose of 60 mg/kg administered once daily is expected to achieve the target fC_max/MIC in 80% of pediatric patients weighing 8-70 kg with a 97.5% probability and almost all patients were predicted to have fC_min < 10 mg/L. However, PK-ARPD simulation predicted that 60 mg/kg/day is unlikely to suppress bacterial resistance with repeated dosing. Furthermore, PK-ARPD simulation suggested that amikacin 90 mg/kg given in two divided doses (45 mg/kg BID) are expected to hit safety and efficacy targets, and associated with a lower rate of bacterial resistance. The disagreement between the two methods is due to the inability of probability approach in predicting development of drug resistance with repeated dosing. This originates from the use of PK-PD indices based on the MIC that neglects measurement errors, ignores the time-course dynamic nature of bacterial growth and killing, and incorrectly assumes the MIC to be constant during treatment.

http://ift.tt/2DtIq05

Evaluating the Relationship between Vancomycin Trough Concentration and 24-Hour Area under the Concentration-Time Curve in Neonates [PublishAheadOfPrint]

Bacterial sepsis is a major cause of morbidity and mortality in neonates, especially those involving methicillin-resistant Staphylococcus aureus (MRSA). Guidelines by the Infectious Diseases Society of America recommend vancomycin 24-hour area under the concentration-time curve to MIC ratio (AUC₂₄/MIC, hr) > 400 as the best predictor of successful treatment against MRSA infections when MIC (mg/L) is ≤ 1. The relationship between steady state vancomycin trough concentrations and AUC₂₄ (mg ⋅ hr/L) has not been studied in an Asian neonatal population. We conducted a retrospective chart review in Singapore hospitals, and collected patient characteristics and therapeutic drug monitoring data from neonates on vancomycin therapy over a 5-year period. A one-compartment population pharmacokinetic model was built from the collected data, internally validated, and then used to assess the relationship between steady state trough concentrations and AUC₂₄. A Monte Carlo simulation sensitivity analysis was also conducted. A total of 76 neonates with 429 vancomycin concentrations were included for analysis. Median (interquartile range) was 30 weeks (28-36 weeks) for postmenstrual age (PMA) and 1043 g (811-1919 g) for weight at initiation of treatment. Vancomycin clearance was predicted by weight, PMA, and serum creatinine. For MRSA isolates with MIC ≤ 1, our major finding was that the minimum steady state trough concentration range predictive of achieving AUC₂₄/MIC > 400 was 8 to 8.9 mg/L. Steady state troughs within 15 to 20 mg/L are unlikely to be necessary to achieve AUC₂₄/MIC > 400, while troughs within 10 to 14.9 mg/L may be more appropriate.

http://ift.tt/2DYJx8S

Tn6450, a novel multidrug resistance transposon characterized in a Proteus mirabilis isolate from chicken in China [PublishAheadOfPrint]

A novel 65.8-kb multidrug resistance transposon, designated as Tn6450, was characterized in a Proteus mirabilis isolate from chicken in China. Tn6450 contains 18 different antimicrobial resistance genes, including cephalosporinase gene bla_DHA-1 and fluoroquinolones resistance genes qnrA1 and aac(6' )-Ib-cr. It carries a class 1/2 hybrid integron composed of intI2 and 3' conserved segment of class 1 integron. Tn6450 is derived from Tn7 via acquisition of new mobile elements and resistance genes.

http://ift.tt/2Dql6A1

Single Intravenous Dose of Oritavancin for the Treatment of Gram-positive Acute Bacterial Skin and Skin Structure Infections: Summary of Safety from the Phase 3 SOLO studies [PublishAheadOfPrint]

Oritavancin is a lipoglycopeptide with bactericidal activity against gram-positive organisms. Its rapid concentration-dependent bactericidal activity and long elimination half-life allow for single dose treatment of acute bacterial skin and skin structure infections (ABSSSI). SOLO I and SOLO II were randomized, double-blind studies evaluating efficacy and safety of a single 1200 mg IV dose of oritavancin versus twice-daily IV vancomycin for 7 to 10 days in ABSSSI patients. Safety data were pooled across both studies for safety analysis. The pooled safety database comprised 976 oritavancin patients and 983 vancomycin patients. The incidence of adverse events, serious adverse events, and discontinuations due to adverse events were similar for oritavancin (55.3, 5.8 and 3.7%, respectively) and vancomycin (56.9, 5.9 and 4.2%, respectively). The median time to onset (3.8 days vs. 3.1 days, respectively) and duration (3.0 days for both groups) of adverse events were also similar between the two groups. The most frequently reported events were nausea, headache, and vomiting. Greater than 90% of all events were mild or moderate in severity. There were slightly more infections and infestation, abscesses or cellulitis, hepatic and cardiac adverse events in the oritavancin group; however, more than 80% of these events were mild or moderate. Subgroup analyses did not identify clinically meaningful differences in the incidence of adverse events attributed to oritavancin. A single 1200 mg dose of oritavancin was well tolerated and had a similar safety profile to twice-daily vancomycin. The long elimination half-life of oritavancin compared to vancomycin did not result in clinically meaningful delay to onset or prolongation of adverse events.

http://ift.tt/2DZ0y2D

FKS2 and FKS3 genes of opportunistic human pathogen Candida albicans influence echinocandin susceptibility [PublishAheadOfPrint]

Candida albicans, a prevailing opportunistic fungal pathogen of humans, has a diploid genome containing three homologous FKS genes that are evolutionary conserved. One of these, the essential gene FKS1, encodes the catalytic subunit of glucan synthase (GS) that is the target of echinocandin drugs and also serves as site of drug resistance. The two other GS-encoding genes, FKS2 and FKS3, are also expressed but their role in resistance is considered unimportant. However, we report here that expression of FKS1 is upregulated in strains lacking either FKS2 or FKS3. Furthermore, in contrast to what is observed in heterozygous FKS1 deletion strains, cells lacking FKS2 or FKS3 contain increased amounts of cell wall glucan, are more resistant to echinocandin drugs and, consistently, are tolerant to cell wall damaging agents. Our data indicate that C. albicans FKS2 and FKS3 can act as negative regulators of FKS1, thereby influencing echinocandin susceptibility.

http://ift.tt/2DsTrP2

Orientia tsutsugamushi is highly susceptible to the RNA polymerase switch region inhibitor Corallopyronin A in vitro and in vivo [PublishAheadOfPrint]

Scrub typhus is a potentially lethal infection caused by the obligate intracellular bacterium Orientia (O.) tsutsugamushi. Reports on the emergence of doxycycline-resistant strains highlight the urgent need to develop novel anti-infectives against scrub typhus.

Corallopyronin A (CorA) is a novel α-pyrone compound synthesized by the myxobacterium Corallococcus coralloides and was characterized as a non-competitive inhibitor of the "switch region" of bacterial RNA polymerase (RNAP). We investigated the antimicrobial action of CorA against the human-pathogenic Karp strain of O. tsutsugamushi in vitro and in vivo. The minimal inhibitory concentration of CorA against O. tsutsugamushi was remarkably low (0.0078 μg/ml), 16-fold lower compared to Rickettsia (R.) typhi. In the lethal intraperitoneal O. tsutsugamushi mouse infection model, a minimum daily dose of 100 μg CorA protected 100% of infected mice. Two days of treatment were sufficient to confer protection. In contrast to BALB/c mice, SCID mice succumbed to the infection despite CorA or tetracycline treatment, suggesting that antimicrobial treatment required synergistic action of the adaptive immune response. Similar to tetracycline, CorA did not prevent latent infection of O. tsutsugamushi in vivo. However, latency was not caused by acquisition of antimicrobial resistance, since O. tsutsugamushi reisolated from latently infected BALB/c mice remained fully susceptible to CorA. No mutations were found in the CorA binding regions of the beta and beta' RNAP subunit genes rpoB and rpoC.

Inhibition of the RNAP switch region of O. tsutsugamushi by CorA is therefore a novel and highly potent target for antimicrobial therapy of scrub typhus.

http://ift.tt/2DWEhm5

Using yeast synthetic lethality to inform drug combination for malaria [PublishAheadOfPrint]

Combinatorial chemotherapy is imperative for the treatment of malaria. However, finding a suitable partner drug for a new candidate is challenging. Here we develop an algorithm that identifies all the gene pairs of Plasmodium falciparum which possess orthologues in yeast that have a synthetic lethal interaction, but are absent in humans. This suggests new options for drug combinations, in particular for inhibitors of targets like P. falciparum calcineurin, cation ATPase 4, or phosphatidylinositol 4-kinase.

http://ift.tt/2DsnIxx

Quantitative analysis of gentamicin exposure in neonates and infants calls into question its current dosing recommendations [PublishAheadOfPrint]

Optimal dosing of gentamicin in neonates is still a matter of debate despite its common use. We identified gentamicin dosing regimens from 8 international guidelines and 7 Swiss Neonatal Intensive Care Units. Dose per administration, dosing interval, total daily dose and demographic characteristics between guidelines were compared. There was considerable variability with respect to dose (4 to 6 mg/kg), dosing interval (24 h to 48 h), total daily dose (2.5 to 6 mg/kg/day) and patient demographic characteristics which were used to calculate individualized dosing regimens. A model-based simulation study in 1071 neonates was performed to determine achievement of efficacious peak gentamicin concentrations according to predefined minimum inhibitory concentrations (MICs) (C_max/MIC ≥ 10) and safe trough concentrations (C_min ≤ 2 mg/L) with recommended dosing regimens. MIC targets of 0.5 and 1 mg/L were used. Dosing optimization was performed giving priority to the first day of treatment and with the goal of simplifying dosing. Current gentamicin neonatal guidelines, achieve effective peak concentrations if MIC is 0.5 mg/L but not for MICs ≥ 1 mg/L. Model-based simulations indicate that to attain peak gentamicin concentrations ≥ 10 mg/L, a dose of 7.5 mg/kg should be administered using an extended dosing interval regimen. Trough concentrations ≤ 2 mg/L can be maintained with a dosing interval of 36 to 48 hours in neonates according to gestational and postnatal age. For treatment beyond 3 days, therapeutic drug monitoring is advised to maintain adequate serum concentrations.

http://ift.tt/2E18D78

The genotoxicity of an aqueous extract of Gyejibokryeong-hwan

Gyejibokryeong-hwan (Guizhi Fuling Wan in China), a mixture of five herbal plants, is a well-known treatment for renal diseases including those associated with climacteric syndrome. However, the genotoxicity of G...

http://ift.tt/2DYURSk

A qualitative study of culturally embedded factors in complementary and alternative medicine use

Within the intercultural milieu of medical pluralism, a nexus of worldviews espousing distinct explanatory models of illness, our research aims at exploring factors leading to complementary and alternative med...

http://ift.tt/2DsSt5m

Neoboutonia melleri var velutina Prain: in vitro and in vivo hepatoprotective effects of the aqueous stem bark extract on acute hepatitis models

Hepatitis is a liver inflammation caused by different agents and remains a public health problem worldwide. Medicinal plants are an important source of new molecules being considered for treatment of this dise...

http://ift.tt/2E1cEsh

Clinical and genomic safety of treatment with Ginkgo biloba L. leaf extract (IDN 5933/Ginkgoselect®Plus) in elderly: a randomised placebo-controlled clinical trial [GiBiEx]

Numerous health benefits have been attributed to the Ginkgo biloba leaf extract (GBLE), one of the most extensively used phytopharmaceutical drugs worldwide. Recently, concerns of the safety of the extract have b...

http://ift.tt/2DtI6hT

Bioactivity of essential oils extracted from Cupressus macrocarpa branchlets and Corymbia citriodora leaves grown in Egypt

Cupressus macrocarpa Hartw and Corymbia citriodora (Hook.) K.D. Hill & L.A.S. Johnson, widely grown in many subtropical areas, are used for commercial purposes, such as in perfumery, cosmetics, and room freshener...

http://ift.tt/2DYSxuL

Beyond Concurrent Chemoradiation: The Emerging Role of PD-1/PD-L1 Inhibitors in Stage III Lung Cancer

Concurrent chemoradiation (cCRT) with platinum-based chemotherapy is standard of care therapy for patients with Stage III unresectable non-small cell lung cancer (NSCLC). Though potentially curative, five-year overall survival has hovered around 20%, despite extensive efforts to improve outcomes with increasing doses of conformal radiation and intensification of systemic therapy with either induction or consolidation chemotherapy. PD-1/PD-L1 immune checkpoint inhibitors have demonstrated unprecedented efficacy in patients with Stage IV NSCLC.  Additionally, preclinical and early clinical evidence suggests that chemotherapy and radiation may work synergistically with anti-PD-1/PD-L1 therapy to promote anti-tumor immunity, which has led to the initiation of clinical trials testing these drugs in patients with Stage III NSCLC. A preliminary report of a randomized phase III trial, the PACIFIC trial, demonstrated an impressive increase in median progression-free survival with consolidative durvalumab, a PD-L1 inhibitor, compared to observation after cCRT. Here, we discuss the clinical and translational implications of integrating PD-1/PD-L1 inhibitors in the management of patients with unresectable Stage III NSCLC.

http://ift.tt/2Dx8IT1

Pembrolizumab plus pegylated interferon alfa-2b or ipilimumab for advanced melanoma or renal cell carcinoma: dose-finding results from the phase 1b KEYNOTE-029 study

Purpose: Pembrolizumab, ipilimumab, and pegylated interferon alfa-2b (PEG-IFN) monotherapy are active against melanoma and renal cell carcinoma (RCC). We explored the safety and preliminary antitumor activity of pembrolizumab combined with either ipilimumab or PEG-IFN in patients with advanced melanoma or RCC. Experimental Design: The phase 1b KEYNOTE-029 study (ClinicalTrials.gov, NCT02089685) included independent pembrolizumab plus reduced-dose ipilimumab and pembrolizumab plus PEG-IFN cohorts. Pembrolizumab 2 mg/kg Q3W plus 4 doses of ipilimumab 1 mg/kg Q3W was tolerable if ≤6/18 patients experienced a dose-limiting toxicity (DLT). The target DLT rate for pembrolizumab 2 mg/kg Q3W plus PEG-IFN was 30%, with a maximum of 14 patients per dose level. Response was assessed per RECIST v1.1 by central review. Results: The ipilimumab cohort enrolled 22 patients, including 19 evaluable for DLTs. Six patients experienced ≥1 DLT. Grade 3-4 treatment-related adverse events occurred in 13 (59%) patients. Responses occurred in 5/12 (42%) patients with melanoma and 3/10 (30%) patients with RCC. In the PEG-IFN cohort, DLTs occurred in 2/14 (14%) patients treated at dose level 1 (PEG-IFN 1 μg/kg/week) and 2/3 (67%) patients treated at dose level 2 (PEG-IFN 2 μg/kg/week). Grade 3-4 treatment-related adverse events occurred in 10/17 (59%) patients. Responses occurred in 1/5 (20%) patients with melanoma and 2/12 (17%) patients with RCC. Conclusions: Pembrolizumab 2 mg/kg Q3W plus ipilimumab 1 mg/kg Q3W was tolerable and provided promising antitumor activity in patients with advanced melanoma or RCC. The maximum tolerated dose of pembrolizumab plus PEG-IFN had limited antitumor activity in this population.

http://ift.tt/2n2ojz0

Glycogen phosphorylase: a novel biomarker in doxorubicin-induced cardiac injury

Extracellular vesicles (EVs) containing glycogen phosphorylase, brain/heart (PYGB) have been demonstrated as a sensitive biomarker for normal cardiac injuries for patients after chemotherapy. Oxidative stress was suggested to be the mechanism behind the chemotherapy-induced tissue damage and augmented with mitochondrial antioxidant could be an effective means of early intervention.

http://ift.tt/2DwYPor

Further investigation of the role of ACYP2 and WFS1 pharmacogenomic variants in the development of cisplatin-induced ototoxicity in testicular cancer patients

Purpose: Adverse drug reactions such as ototoxicity, which occurs in approximately one fifth of adult patients who receive cisplatin treatment, can incur large socio-economic burdens on testicular cancer patients who develop this cancer during early adulthood. Recent genome-wide association studies have identified genetic variants in ACYP2 and WFS1 that are associated with cisplatin-induced ototoxicity. We sought to explore the role of these genetic susceptibility factors to cisplatin-induced ototoxicity in testicular cancer patients. Experimental Design: Extensive clinical and demographic data were collected for 229 testicular cancer patients treated with cisplatin. Patients were genotyped for two variants, ACYP2 rs1872328 and WFS1 rs62283056, that have previously been associated with hearing loss in cisplatin-treated patients. Analyses were performed to investigate the association of these variants with ototoxicity in this cohort of adult testicular cancer patients. Results: Pharmacogenomic analyses revealed that ACYP2 rs1872328 was significantly associated with cisplatin-induced ototoxicity (P=2.83x10-3, OR[95%C]:14.7[2.6-84.2]). WFS1 rs62283056 was not significantly associated with ototoxicity caused by cisplatin (P=0.39); however, this variant was associated with hearing loss attributable to any cause (P=5.67x10-3, OR[95%CI]:3.2[1.4-7.7]). Conclusions: This study has provided the first evidence for the role of ACYP2 rs1872328 in cisplatin-induced ototoxicity in testicular cancer patients. These results support the use of this information to guide the development of strategies to prevent cisplatin-induced ototoxicity across cancers. Further, this study has highlighted the importance of phenotypic differences in replication studies and has provided further evidence for the role of WFS1 rs62283056 in susceptibility to hearing loss, which may be worsened by cisplatin treatment.

http://ift.tt/2n2rTsZ

Safety, activity and biomarkers of SHR-1210, an anti-PD-1 antibody, for patients with advanced esophageal carcinoma

Purpose: The current management of advanced esophageal squamous cell carcinoma (ESCC) remains unsatisfactory. We investigated the safety, efficacy and biomarkers of SHR-1210, an anti-PD-1 antibody, in patients with recurrent or metastatic ESCC. Experimental Design: This study was a part of phase 1 trial in China. Patients with advanced ESCC who were refractory or intolerant to previous chemotherapy were enrolled. Eligible patients received intravenous SHR-1210 at a dose of 60 mg, with escalation to 200mg and 400 mg (4-week interval after first dose followed by a 2-week schedule) until disease progression or intolerable toxicity. The associations between candidate biomarkers (PD-L1 and somatic mutation load) and the efficacy of SHR-1210 were also explored. Results: Between May 11, 2016 and December 9, 2016, a total of 30 patients from one site in China were enrolled. Ten patients (33.3%) had an independently assessed objective response. Median progression free survival was 3.6 months (95% CI: 0-7.2). Three (10.0%) treatment-related grade 3 adverse events were reported: two (6.7%) pneumonitis and one (3.3%) increased cardiac troponin I. No grade 4 or grade 5 treatment-related adverse events were reported. The exome sequencing and analysis showed that the mutational burden and the potential mutation-associated neoantigen count were associated with better responses. An objective response was more common in patients with PD-L1-positive tumors as defined by >5% staining (7 of 15 patients) than in those with PD-L1-negative tumors (1 of 9 patients). Conclusion: In this population of ESCC patients, SHR-1210 had a manageable safety profile and promising antitumor activity.

http://ift.tt/2Dwud6j

Alzheimer’s disease diagnosis based on the Hippocampal Unified Multi-Atlas Network (HUMAN) algorithm

Hippocampal atrophy is a supportive feature for the diagnosis of probable Alzheimer's disease (AD). However, even for an expert neuroradiologist, tracing the hippocampus and measuring its volume is a time cons...

http://ift.tt/2n1qBiG

Semitransparent bandages based on chitosan and extracellular matrix for photochemical tissue bonding

Extracellular matrices (ECMs) are often used in reconstructive surgery to enhance tissue regeneration and remodeling. Sutures and staples are currently used to fix ECMs to tissue although they can be invasive ...

http://ift.tt/2Bmysvw

Selective mTORC2 inhibitor therapeutically blocks breast cancer cell growth and survival

Small molecule inhibitors of the mTORC2 kinase (torkinibs) have shown efficacy in early clinical trials. However, the torkinibs under study also inhibit the other mTOR-containing complex mTORC1. While mTORC1/mTORC2 combined inhibition may be beneficial in cancer cells, recent reports describe compensatory cell survival upon mTORC1 inhibition due to loss of negative feedback on PI3K, increased autophagy, and increased macropinocytosis. Genetic models suggest that selective mTORC2 inhibition would be effective in breast cancers, but the lack of selective small molecule inhibitors of mTORC2 have precluded testing of this hypothesis to date. Here we report the engineering of a nanoparticle-based RNAi therapeutic that can effectively silence the mTORC2 obligate cofactor Rictor. Nanoparticle-based Rictor ablation in HER2-amplified breast tumors was achieved following intra-tumoral and intra-venous delivery, decreasing Akt phosphorylation and increasing tumor cell killing. Selective mTORC2 inhibition in vivo, combined with the HER2 inhibitor lapatinib, decreased the growth of HER2-amplified breast cancers to a greater extent than either agent alone, suggesting that mTORC2 promotes lapatinib resistance but is overcome by mTORC2 inhibition. Importantly, selective mTORC2 inhibition was effective in a TNBC model, decreasing Akt phosphorylation and tumor growth, consistent with our findings that RICTOR mRNA correlates with worse outcome in patients with basal-like TNBC. Together, our results offer preclinical validation of a novel RNAi delivery platform for therapeutic gene ablation in breast cancer, and they show that mTORC2-selective targeting is feasible and efficacious in this disease setting.

http://ift.tt/2DsgOZb

Small molecule activators of protein phosphatase 2A for the treatment of castration-resistant prostate cancer.

Primary prostate cancer is generally treatable by androgen deprivation therapy, however, later recurrences of castrate-resistant prostate cancer (CRPC) that is more difficult to treat nearly always occurs due to aberrant re-activation of the androgen receptor (AR). In this study, we report that CRPC cells are particularly sensitive to the growth inhibitory effects of re-engineered tricyclic sulfonamides, a class of molecules that activate the protein phosphatase PP2A which inhibits multiple oncogenic signaling pathways. Treatment of CRPC cells with small molecule activators of PP2A (SMAP) in vitro decreased cellular viability and clonogenicity and induced apoptosis. SMAP treatment also induced an array of significant changes in the phosphoproteome, including most notably dephosphorylation of full-length and truncated isoforms of the AR and downregulation of its regulatory kinases in a dose-dependent and time-dependent manner. In murine xenograft models of human CRPC, the potent compound SMAP-2 exhibited efficacy comparable to enzalutamide in inhibiting tumor formation. Overall, our results provide a preclinical proof of concept for the efficacy of SMAP in AR degradation and CRPC treatment.

http://ift.tt/2DYTEuk

2-hydroxyglutarate-mediated autophagy of the endoplasmic reticulum leads to an unusual downregulation of phospholipid biosynthesis in mutant IDH1 gliomas

Tumor metabolism is reprogrammed to meet the demands of proliferating cancer cells. In particular, cancer cells upregulate synthesis of the membrane phospholipids phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdE) in order to allow for rapid membrane turnover. Nonetheless, we show here that, in mutant isocitrate dehydrogenase 1 (IDHmut) gliomas, which produce the oncometabolite 2-hydroxyglutarate (2-HG), PtdCho and PtdE biosynthesis is downregulated and results in lower levels of both phospholipids when compared to wild-type IDH1 cells. 2-HG inhibited collagen-4-prolyl hydroxylase activity, leading to accumulation of misfolded procollagen-IV in the endoplasmic reticulum (ER) of both genetically engineered and patient-derived IDHmut glioma models. The resulting ER stress triggered increased expression of FAM134b, which mediated autophagic degradation of the ER (ER-phagy) and a reduction in ER area. Because the ER is the site of phospholipid synthesis, ER-phagy led to reduced PtdCho and PtdE biosynthesis. Inhibition of ER-phagy via pharmacological or molecular approaches restored phospholipid biosynthesis in IDHmut glioma cells, triggered apoptotic cell death, inhibited tumor growth and prolonged the survival of orthotopic IDHmut glioma-bearing mice, pointing to a potential therapeutic opportunity. Glioma patient biopsies also exhibited increased ER-phagy and downregulation of PtdCho and PtdE levels in IDHmut samples compared to wild-type, clinically validating our observations. Collectively, this study provides detailed and clinically-relevant insights into the functional link between oncometabolite-driven ER-phagy and phospholipid biosynthesis in IDHmut gliomas.

http://ift.tt/2DroE58

Message from the new editors of Arquivos de Neuro-Psiquiatria

http://ift.tt/2E0oKlv

Non-inflammatory cerebrospinal fluid delays the diagnosis and start of immunotherapy in anti-NMDAR encephalitis

ABSTRACT Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a form of autoimmune encephalopathy that presents with a wide variety of symptoms, including neuropsychiatric manifestations. The authors' aim for this study was to analyze the results of paraclinical studies of patients with a diagnosis of anti-NMDAR encephalitis and the association between symptom onset and diagnosis, and start of immunotherapy. Retrospective data of 29 patients with anti-NMDAR encephalitis were gathered and analyzed. Abnormal EEG was found in 27 patients (93.1%), whereas MRI was abnormal in 19 patients (65.5%). In contrast, an inflammatory pattern on CSF analysis was found in only 13 patients (44.8%). The absence of pleocytosis or increased proteins in the CSF was associated with a longer time from symptom onset to diagnosis and treatment (p = 0.003). The authors conclude that noninflammatory CSF may delay the correct diagnosis and start of immunotherapy in anti-NMDAR encephalitis. In the presence of suggestive clinical features, extensive studies including EEG are recommended.

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RESUMEN La encefalitis por receptor anti-N-metil-D-aspartato (anti-NMDAR) es una encefalopatía autoinmune con una amplia variedad de síntomas, incluyendo manifestaciones neuropsiquiátricas. Nuestro objetivo en este estudio fue analizar los resultados paraclínicos de pacientes diagnosticados con encefalitis anti-NMDAR y la asociación entre inicio de sintomatología, el diagnóstico y el inicio de inmunoterapia. Encontramos un EEG anormal en 27 pacientes (93.1%), así como IRM anormal en 19 de ellos (65.5%). En contraste, el análisis de LCR mostró un patrón inflamatorio en tan solo 13 pacientes (44.8%). La ausencia de pleocitosis o proteínas incrementadas en el LCR se asoció con un mayor tiempo desde el inicio de la sintomatología hasta el inicio del tratamiento (p=0.003). Concluimos que el LCR no inflamatorio puede retrasar el diagnóstico correcto y el inicio de tratamiento en encefalitis anti-NMDAR, por lo que se recomienda la realización de estudios exhaustivos, incluyendo EEG, ante la presencia de indicadores clínicos sugerentes del padecimiento.

http://ift.tt/2DrtIXa

Multiple sclerosis risk perception and acceptance for Brazilian patients

ABSTRACT The perception of multiple sclerosis (MS) severity and risk associated with therapies might influence shared decision making in different countries. We investigated the perception of MS severity and factors associated with risk acceptance in Brazil in 96 patients with relapsing-remitting MS using a standardized questionnaire and compared this with two European cohorts. Multiple sclerosis was perceived as a very severe disease and the risk of developing progressive multifocal leukoencephalopathy due to natalizumab was seen as moderate to high. Seventy-six percent considered a risk of 1:1,000, or higher, an impediment for natalizumab use. Older age was the only variable associated with higher risk acceptance and our patients showed a more conservative profile than German and Spanish patients. Our patients perceived MS severity and progressive multifocal leukoencephalopathy risk similarly to elsewhere, but their willingness to take risks was more conservative. This should be considered when discussing therapeutic options and it might have an impact on guideline adaptations.

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RESUMO A percepção de gravidade da esclerose múltipla (EM) e riscos associado a terapias podem influenciar a escolha de tratamento em diferentes países. Investigamos a percepção da gravidade da EM e fatores associados à aceitação de risco em 96 pacientes com EM remitente-recorrentecom um questionário e comparamos com duas coortes europeias. A EM foi percebida como muito grave e o risco de desenvolver leucoencefalopatia multifocal progressiva devido ao natalizumabe, como moderado a alto, sendo que76% consideraram um risco de 1: 1.000 ou maior como impeditivo deseu uso. Idade mais avançada foi a única variável associada àaceitação de risco mais elevado e nossos pacientes revelaram um perfil mais conservador do que os pacientes alemães e espanhóis. Esses dados devem ser considerados ao discutir opções terapêuticas e pode ter impacto nas adaptações de diretrizes locais.

http://ift.tt/2E1yNH1

Medical perception of stroke care conditions in Brazil

ABSTRACT Stroke is currently the second leading cause of death in Brazil. Neurologists' reports on the absence of adequate resources for stroke care are frequent; however, there are no objective data on this perception. Objective To assess the perception of neurologists of stroke care conditions in Brazil. Methods Neurologists from all over Brazil were surveyed by means of an anonymous questionnaire about the main shortcomings in stroke care, focusing particularly on physical structure and infrastructure (diagnostic methods, patient transport, availability of beds, multi-professional team). Results The main shortcomings are indicated: the worst conditions, among all items surveyed, were found in the public sector. In the private sector, conditions were better. Conclusions Care conditions are worse in the public sector with regard to both infrastructure and human resources. Future public health policies for the prevention and treatment of stroke should be formulated, taking into consideration neurologists' perceptions.

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RESUMO O acidente vascular cerebral é atualmente a segunda causa de morte no Brasil. São frequentes os relatos de médicos neurologistas sobre a ausência de recursos adequados para o atendimento do AVC, no entanto, não existem dados objetivos sobre essa percepção. Objetivo Analisar a percepção de médicos neurologistas sobre as condições para o atendimento de AVC no Brasil. Métodos Neste estudo foi realizada pesquisa por questionário anônimo com médicos neurologistas de todo o Brasil, perguntando-se as principais deficiências para o atendimento, com foco na estrutura física, infraestrutura (métodos diagnósticos, transporte do doente, disponibilidade de leitos, equipe multiprofissional). Resultados As principais deficiências são apontadas; no setor público notou-se as piores condições, em todos os itens pesquisados. No setor privado, as condições são melhores. Conclusões As condições de atendimento são piores no setor público, tanto de infraestrutura quanto de recursos humanos. Futuras políticas de saúde pública para prevenção e tratamento do AVC deveriam ser elaboradas levando em consideração a percepção do neurologista.

http://ift.tt/2DqHt8z

Anticoagulation in patients with cardiac manifestations of Chagas disease and cardioembolic ischemic stroke

ABSTRACT Objectives To describe anticoagulation characteristics in patients with cardiac complications from Chagas disease and compare participants with and without cardioembolic ischemic stroke (CIS). Methods A retrospective cohort of patients with Chagas disease, using anticoagulation, conducted from January 2011 to December 2014. Results Forty-two patients with Chagas disease who were using anticoagulation were studied (age 62.9±12.4 years), 59.5% female and 47.6% with previous CIS, 78.6% with non-valvular atrial fibrillation and 69.7% with dilated cardiomyopathy. Warfarin was used in 78.6% of patients and dabigatran (at different times) in 38%. In the warfarin group, those with CIS had more medical appointments per person-years of follow-up (11.7 vs 7.9), a higher proportion of international normalized ratios within the therapeutic range (57% vs 42% medical appointments, p = 0.025) and an eight times higher frequency of minor bleeding (0.64 vs 0.07 medical appointments). Conclusion Patients with Chagas disease and previous CIS had better control of INR with a higher frequency of minor bleeding.

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RESUMO Objetivos descrever as características da anticoagulação em pacientes com manifestações cardíacas da doença de Chagas (MCDC) e comparar os participantes com sem acidente vascular cerebral isquêmico cardioembólico (AVCIC). Resultados 42 pacientes com MCDC em anticoagulação foram estudados (62,9 ± 12,4 anos), 59,5% do sexo feminino e 47,6% com AVCIC prévio, 78,6% portadores de fibrilação atrial não valvar e 69,7% com cardiomiopatia dilatada. Varfarina foi utilizada em 78,6% dos pacientes e dabigatrana em 38% (em momentos diferentes). No grupo da varfarina, aqueles com AVCIC tiveram mais consultas médicas por pessoas-ano de seguimento (11,7 vs 7,9), maior taxa de RNI na faixa terapêutica (57% vs 42% consultas médicas, p = 0,025) e uma frequência oito vezes maior de sangramento menor (0,64 vs. 0,07 consultas médicas). Conclusão pacientes com MCDC e AVCIC prévio têm melhor controle de RNI com maior frequência de sangramento menor.

http://ift.tt/2DYv7FI

A Brazilian-Portuguese version of the Kinesthetic and Visual Motor Imagery Questionnaire

ABSTRACT Motor imagery has emerged as a potential rehabilitation tool in stroke. The goals of this study were: 1) to develop a translated and culturally-adapted Brazilian-Portugese version of the Kinesthetic and Visual Motor Imagery Questionnaire (KVIQ20-P); 2) to evaluate the psychometric characteristics of the scale in a group of patients with stroke and in an age-matched control group; 3) to compare the KVIQ20 performance between the two groups. Methods Test-retest, inter-rater reliabilities, and internal consistencies were evaluated in 40 patients with stroke and 31 healthy participants. Results In the stroke group, ICC confidence intervals showed excellent test-retest and inter-rater reliabilities. Cronbach's alpha also indicated excellent internal consistency. Results for controls were comparable to those obtained in persons with stroke. Conclusions The excellent psychometric properties of the KVIQ20-P should be considered during the design of studies of motor imagery interventions for stroke rehabilitation.

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RESUMO A Imagética Mental é uma ferramenta em potencial para a reabilitação de indivíduos com doenças cerebrovasculares. Os objetivos desse estudo foram: 1) Desenvolver uma versão traduzida e adaptada culturalmente do Questionário de Imagética Motora Cinestésica e Visual (KVIQ20-P); 2) Avaliar as características psicométricas da escala nesse grupo e em controles; 3) Comparar o desempenho na escala entre os dois grupos. Métodos Confiabilidades teste-reteste, interexaminador, assim como consistências internas da KVIQ20-P foram avaliadas em 40 indivíduos com AVC e em 31 controles. Resultados No grupo de pacientes, os intervalos de confiança mostraram excelentes confiabilidades teste-reteste e interexaminador. O alfa de Cronbach indicou uma excelente consistência interna. Os resultados no grupo controle foram comparáveis aos obtidos nos pacientes. Conclusões As excelentes propriedades psicométricas da KVIQ20-P devem ser consideradas durante o desenho de estudos de Imagética Mental para a reabilitação de indivíduos com doenças cerebrovasculares.

http://ift.tt/2Dtgfy5

Thymoquinone reverses learning and memory impairments and brain tissue oxidative damage in hypothyroid juvenile rats

ABSTRACT In this study, the effect of thymoquinone (TQ) on propylthiouracil (PTU)-induced memory impairment was investigated in juvenile rats. The rats were grouped into control, Hypo, Hypo-TQ5 and Hypo-TQ10. Propylthiouracil increased latency time in the Morris water maze test and decreased delay in entering the dark compartment in the passive avoidance test. Both 5 mg/kg and 10 mg/kg doses of TQ decreased latency time in the Morris water maze test and increased delay in entering the dark compartment in a passive avoidance test. The PTU also increased malondialdehyde and nitric oxide metabolites in the brain while reduced the thiol content and superoxide dismutase and catalase activities and serum T4 level. Both doses of TQ decreased malondialdehyde and nitric oxide metabolites in the brain while enhanced the thiol content and superoxide dismutase and catalase activities and serum T4 level. The results of the present study showed that TQ protected against PTU-induced memory impairments in rats.

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RESUMO Neste estudo, foi investigado o efeito da timoquinona (TQ) contra deficiências de memória induzidas por propiltiouracilo (PTU) em ratos juvenis. Os ratos foram agrupados em grupos: controle, Hypo, Hypo-TQ5, e Hypo-TQ10. O PTU aumentou o tempo de latência no teste do labirinto aquático de Morris (MWM) e diminuiu o atraso para entrar no compartimento escuro no teste de evasão passiva (PA). Ambas as doses de TQ diminuíram o tempo de latência no teste de MWM e aumentaram o atraso para entrar no compartimento escuro no teste de PA. O PTU também aumentou os metabolitos de malondialdeído (MDA) e óxido nítrico (NO) no cérebro, enquanto reduziu o teor de tiol e as atividades de superóxido dismutasa (SOD) e catalasa (CAT) e o nível sérico de T4. Ambas as doses de TQ diminuíram os metabolitos de MDA e de NO no cérebro, aumentaram o conteúdo de tiol e as atividades de SOD e CAT e o nível de T4 no soro. Os resultados do presente estudo mostraram que a TQ protegeu contra deficiências de memória induzidas por PTU em ratos.

http://ift.tt/2E2bJaM

Autoimmune encephalitis: a review of diagnosis and treatment

ABSTRACT Autoimmune encephalitis (AIE) is one of the most common causes of noninfectious encephalitis. It can be triggered by tumors, infections, or it may be cryptogenic. The neurological manifestations can be either acute or subacute and usually develop within six weeks. There are a variety of clinical manifestations including behavioral and psychiatric symptoms, autonomic disturbances, movement disorders, and seizures. We reviewed common forms of AIE and discuss their diagnostic approach and treatment.

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RESUMO As encefalites autoimunes (EAI) são a principal causa de encefalite não-infecciosa. As manifestações neurológicas são variadas, incluindo alterações comportamentais ou psiquiátricas, disautonomia, transtornos do movimento e epilepsia. Habitualmente a instalação dos sintomas ocorre em até 6 semanas, de forma aguda ou subaguda. As EAI podem ser desencadeadas por tumores, quadros infecciosos virais ou ainda apresentar etiologia criptogênica. Este artigo revisa as principais EAI, estratégias de diagnóstico e tratamento.

http://ift.tt/2Dpwr3r

Arquivos de Neuro-Psiquiatria: 75 years

ABSTRACT This year marks the 75th year of publication of Arquivos de Neuro-Psiquiatria (ANP), the official journal of the Brazilian Academy of Neurology and one of the most important neuroscience journals in Latin America. ANP was initially edited by Oswaldo Lange, its founder, and subsequently by Antonio Spina-França Netto and, in recent years, by José Antonio Livramento and Luís dos Ramos Machado.

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RESUMO Arquivos de Neuro-Psiquiatria (ANP), o periódico oficial da Academia Brasileira de Neurologia, completou 75 anos de atividades, reconhecido como um dos jornais de neurociências mais importante da América Latina. Nestes 75 anos de existência o ANP teve como editores os Professores Oswaldo Lange, o seu fundador, seguido por Antonio Spina-França Netto, e nos últimos anos, José Antonio Livramento e Luís dos Ramos Machado.

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Searching for neurological diseases in the Julio-Claudian dynasty of the Roman Empire

ABSTRACT The gens Julia was one of the oldest families in ancient Rome, whose members reached the highest positions of power. They made history because Julius Caesar, perpetual dictator, great-uncle of the first emperor, Augustus, passed his name on to the Julio-Claudian dynasty with the emperors Tiberius, Caligula, Claudius and Nero. Descriptions of the diseases of these emperors and some of his family members may indicate diagnoses such as epilepsy, dystonia, dementia, encephalitis, neurosyphilis, peripheral neuropathies, dyslexia, migraine and sleep disorders. In the historical context of ancient Rome, the possibility of infectious diseases related to the libertine way of life is quite large. However, there is a possibility that some of these diseases occurred from genetic transmission.

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RESUMO A gens Iulia era uma das mais antigas famílias da Roma Antiga, com membros que chegaram aos mais altos cargos. Ficaram na história por causa de Julius Caesar, ditador perpétuo, pai adotivo do primeiro imperador Augustus, por meio de quem seu nome passou para a dinastia Julio-Claudian com os imperadores Tiberius, Caligula, Claudius e Nero. Descrições de doenças desses imperadores e de alguns de seus familiares podem nos remeter a diagnósticos como epilepsia, distonia, demência, encefalites, neurossífilis, neuropatias periféricas, dislexia, migrânea e distúrbios do sono. No contexto histórico da Roma antiga, a possibilidade de doenças infecciosas e relacionadas ao modo de vida libertino é bastante grande. Entretanto, existe a possibilidade de que algumas dessas doenças tenham ocorrido por transmissão genética.

http://ift.tt/2Dos8oX

“Acute Dupuytren’s contracture”: the answer is not always in your hands

ABSTRACT The gens Julia was one of the oldest families in ancient Rome, whose members reached the highest positions of power. They made history because Julius Caesar, perpetual dictator, great-uncle of the first emperor, Augustus, passed his name on to the Julio-Claudian dynasty with the emperors Tiberius, Caligula, Claudius and Nero. Descriptions of the diseases of these emperors and some of his family members may indicate diagnoses such as epilepsy, dystonia, dementia, encephalitis, neurosyphilis, peripheral neuropathies, dyslexia, migraine and sleep disorders. In the historical context of ancient Rome, the possibility of infectious diseases related to the libertine way of life is quite large. However, there is a possibility that some of these diseases occurred from genetic transmission.

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RESUMO A gens Iulia era uma das mais antigas famílias da Roma Antiga, com membros que chegaram aos mais altos cargos. Ficaram na história por causa de Julius Caesar, ditador perpétuo, pai adotivo do primeiro imperador Augustus, por meio de quem seu nome passou para a dinastia Julio-Claudian com os imperadores Tiberius, Caligula, Claudius e Nero. Descrições de doenças desses imperadores e de alguns de seus familiares podem nos remeter a diagnósticos como epilepsia, distonia, demência, encefalites, neurossífilis, neuropatias periféricas, dislexia, migrânea e distúrbios do sono. No contexto histórico da Roma antiga, a possibilidade de doenças infecciosas e relacionadas ao modo de vida libertino é bastante grande. Entretanto, existe a possibilidade de que algumas dessas doenças tenham ocorrido por transmissão genética.

http://ift.tt/2BkNPnW

Proximal limb weakness and amyotrophy in a man with silicosis

ABSTRACT The gens Julia was one of the oldest families in ancient Rome, whose members reached the highest positions of power. They made history because Julius Caesar, perpetual dictator, great-uncle of the first emperor, Augustus, passed his name on to the Julio-Claudian dynasty with the emperors Tiberius, Caligula, Claudius and Nero. Descriptions of the diseases of these emperors and some of his family members may indicate diagnoses such as epilepsy, dystonia, dementia, encephalitis, neurosyphilis, peripheral neuropathies, dyslexia, migraine and sleep disorders. In the historical context of ancient Rome, the possibility of infectious diseases related to the libertine way of life is quite large. However, there is a possibility that some of these diseases occurred from genetic transmission.

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RESUMO A gens Iulia era uma das mais antigas famílias da Roma Antiga, com membros que chegaram aos mais altos cargos. Ficaram na história por causa de Julius Caesar, ditador perpétuo, pai adotivo do primeiro imperador Augustus, por meio de quem seu nome passou para a dinastia Julio-Claudian com os imperadores Tiberius, Caligula, Claudius e Nero. Descrições de doenças desses imperadores e de alguns de seus familiares podem nos remeter a diagnósticos como epilepsia, distonia, demência, encefalites, neurossífilis, neuropatias periféricas, dislexia, migrânea e distúrbios do sono. No contexto histórico da Roma antiga, a possibilidade de doenças infecciosas e relacionadas ao modo de vida libertino é bastante grande. Entretanto, existe a possibilidade de que algumas dessas doenças tenham ocorrido por transmissão genética.

http://ift.tt/2n3iGkI

Delayed hemiparkinsonism after closed head injury

ABSTRACT The gens Julia was one of the oldest families in ancient Rome, whose members reached the highest positions of power. They made history because Julius Caesar, perpetual dictator, great-uncle of the first emperor, Augustus, passed his name on to the Julio-Claudian dynasty with the emperors Tiberius, Caligula, Claudius and Nero. Descriptions of the diseases of these emperors and some of his family members may indicate diagnoses such as epilepsy, dystonia, dementia, encephalitis, neurosyphilis, peripheral neuropathies, dyslexia, migraine and sleep disorders. In the historical context of ancient Rome, the possibility of infectious diseases related to the libertine way of life is quite large. However, there is a possibility that some of these diseases occurred from genetic transmission.

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RESUMO A gens Iulia era uma das mais antigas famílias da Roma Antiga, com membros que chegaram aos mais altos cargos. Ficaram na história por causa de Julius Caesar, ditador perpétuo, pai adotivo do primeiro imperador Augustus, por meio de quem seu nome passou para a dinastia Julio-Claudian com os imperadores Tiberius, Caligula, Claudius e Nero. Descrições de doenças desses imperadores e de alguns de seus familiares podem nos remeter a diagnósticos como epilepsia, distonia, demência, encefalites, neurossífilis, neuropatias periféricas, dislexia, migrânea e distúrbios do sono. No contexto histórico da Roma antiga, a possibilidade de doenças infecciosas e relacionadas ao modo de vida libertino é bastante grande. Entretanto, existe a possibilidade de que algumas dessas doenças tenham ocorrido por transmissão genética.

http://ift.tt/2BnGww8

Rapidly progressive subacute motor neuronopathy disclosing type B2 thymoma

ABSTRACT The gens Julia was one of the oldest families in ancient Rome, whose members reached the highest positions of power. They made history because Julius Caesar, perpetual dictator, great-uncle of the first emperor, Augustus, passed his name on to the Julio-Claudian dynasty with the emperors Tiberius, Caligula, Claudius and Nero. Descriptions of the diseases of these emperors and some of his family members may indicate diagnoses such as epilepsy, dystonia, dementia, encephalitis, neurosyphilis, peripheral neuropathies, dyslexia, migraine and sleep disorders. In the historical context of ancient Rome, the possibility of infectious diseases related to the libertine way of life is quite large. However, there is a possibility that some of these diseases occurred from genetic transmission.

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RESUMO A gens Iulia era uma das mais antigas famílias da Roma Antiga, com membros que chegaram aos mais altos cargos. Ficaram na história por causa de Julius Caesar, ditador perpétuo, pai adotivo do primeiro imperador Augustus, por meio de quem seu nome passou para a dinastia Julio-Claudian com os imperadores Tiberius, Caligula, Claudius e Nero. Descrições de doenças desses imperadores e de alguns de seus familiares podem nos remeter a diagnósticos como epilepsia, distonia, demência, encefalites, neurossífilis, neuropatias periféricas, dislexia, migrânea e distúrbios do sono. No contexto histórico da Roma antiga, a possibilidade de doenças infecciosas e relacionadas ao modo de vida libertino é bastante grande. Entretanto, existe a possibilidade de que algumas dessas doenças tenham ocorrido por transmissão genética.

http://ift.tt/2n3iu4Y

Incidence of Guillain-Barré syndrome among Zika virus infected cases: a report from Thailand

ABSTRACT The gens Julia was one of the oldest families in ancient Rome, whose members reached the highest positions of power. They made history because Julius Caesar, perpetual dictator, great-uncle of the first emperor, Augustus, passed his name on to the Julio-Claudian dynasty with the emperors Tiberius, Caligula, Claudius and Nero. Descriptions of the diseases of these emperors and some of his family members may indicate diagnoses such as epilepsy, dystonia, dementia, encephalitis, neurosyphilis, peripheral neuropathies, dyslexia, migraine and sleep disorders. In the historical context of ancient Rome, the possibility of infectious diseases related to the libertine way of life is quite large. However, there is a possibility that some of these diseases occurred from genetic transmission.

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RESUMO A gens Iulia era uma das mais antigas famílias da Roma Antiga, com membros que chegaram aos mais altos cargos. Ficaram na história por causa de Julius Caesar, ditador perpétuo, pai adotivo do primeiro imperador Augustus, por meio de quem seu nome passou para a dinastia Julio-Claudian com os imperadores Tiberius, Caligula, Claudius e Nero. Descrições de doenças desses imperadores e de alguns de seus familiares podem nos remeter a diagnósticos como epilepsia, distonia, demência, encefalites, neurossífilis, neuropatias periféricas, dislexia, migrânea e distúrbios do sono. No contexto histórico da Roma antiga, a possibilidade de doenças infecciosas e relacionadas ao modo de vida libertino é bastante grande. Entretanto, existe a possibilidade de que algumas dessas doenças tenham ocorrido por transmissão genética.

http://ift.tt/2BjwRqm

Ectoparasites associated with small mammals (orders Insectivora, Eulipotyphla, and Rodentia) in Razan plain, western region of Iran

Abstract

There is a wide distribution of small mammals all over the world and they harbor a large number of ectoparasites. The objectives of this project were to determine the prevalence and intensity of ectoparasites of small mammals in the Razan plain region. From February 2010 to November 2013, small mammals were collected by live traps. Animals were anesthetized and ectoparasites were collected, preserved in ethanol, and then identified. A total of 192 small mammals in five species including three species of rodents, one species of shrew, and one species of hedgehog were caught of which ultimately 13 species of ectoparasites were collected: three species of sucking lice, four species of fleas, and six species of ticks. In total, 62.5% of small mammals were infested with at least one species of ectoparasites. Statistical analysis did not show any significant relationship between gender and ectoparasites (p ˃ 0.05). Also, no significant correlation was found between altitude and the parasite abundance (Spearman's test: p > 0.05). The results of the present study indicated high infestation of small mammals and their potential for zoonosis in the Razan plain.

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