The importance of data structure in statistical analysis of dendritic spine morphology

Publication date: 15 February 2018
Source:Journal of Neuroscience Methods, Volume 296
Author(s): Veerle Paternoster, Anto P. Rajkumar, Jens Randel Nyengaard, Anders Dupont Børglum, Jakob Grove, Jane Hvarregaard Christensen
BackgroundDendritic spine morphology is heterogeneous and highly dynamic. To study the changing or aberrant morphology in test setups, often spines from several neurons from a few experimental units e.g. mice or primary neuronal cultures are measured. This strategy results in a multilevel data structure, which, when not properly addressed, has a high risk of producing false positive and false negative findings.MethodsWe used mixed-effects models to deal with data with a multilevel data structure and compared this method to analyses at each level. We apply these statistical tests to a dataset of dendritic spine morphology parameters to illustrate advantages of multilevel mixed-effects model, and disadvantages of other models.ResultsWe present an application of mixed-effects models for analyzing dendritic spine morphology datasets while correcting for the data structure.Comparison with existing methodsWe further show that analyses at spine level and aggregated levels do not adequately account for the data structure, and that they may lead to erroneous results.ConclusionWe highlight the importance of data structure in dendritic spine morphology analyses and highly recommend the use of mixed-effects models or other appropriate statistical methods to deal with multilevel datasets. Mixed-effects models are easy to use and superior to commonly used methods by including the data structure and the addition of other explanatory variables, for example sex, and age, etc., as well as interactions between variables or between variables and level identifiers.



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Simultaneous quantification of caffeine and chlorogenic acid in coffee green beans and varietal classification of the samples by HPLC-DAD coupled with chemometrics

Abstract

A chromatographic procedure (HPLC-DAD) using a relatively rapid gradient has been combined with a chemometric curve deconvolution method, multivariate curve resolution-alternating least squares (MCR-ALS), in order to quantify caffeine and chlorogenic acid in green coffee beans. Despite that the HPLC analysis (at these specific operating conditions) presents some coeluting peaks, MCR-ALS allowed their resolution and, consequently, the creation of a calibration curve to be used for the quantification of the analytes of interest; this procedure led to a high accuracy in the quantification of caffeine and chlorogenic acid present in the samples. In a second part of this study, the possibility of classifying the green coffee beans on the basis of their cultivar (Arabica or Robusta), by partial least squares discriminant analysis (PLS-DA) and soft independent modeling of class analogies (SIMCA), has been explored. SIMCA resulted in 100% of sensitivity and specificity for the Arabica class, while for the Robusta, it reached 66.7% of sensitivity and 100% of specificity, or 100% of sensitivity and 100% of specificity, depending on the extraction procedure followed prior to the chromatographic analysis; PLS-DA achieved 100% of correct classification independently of the procedure used for the extraction.

http://ift.tt/2nUUbG6

Wet deposition of atmospheric nitrogen contributes to nitrogen loading in the surface waters of Lake Tanganyika, East Africa: a case study of the Kigoma region

Abstract

Lake Tanganyika, an African Great Lake, is a complex tropical ecosystem that has been subjected to extreme climate-related changes in the last century, including seasonal changes in temperature and rainfall, decreased overall annual rainfall, and greater frequency of rainstorms. Atmospheric nitrogen (N) is an important component of the lake's N loading, but how long-term and seasonal changes in precipitation affect this loading still needs clarification. This study aimed to improve our understanding of the seasonal features of N deposition in the lake, by monitoring atmospheric N deposition concentrations and fluxes from March 2013 to February 2014. There was a significant temporal variation in wet N depositions in the study area. The distribution of the annual rainfall into major (March–May 299.8 mm) and minor (October–December 343.2 mm) rainy seasons translated into 20 and 30% of N deposition. In September and January–February, there was 10 and 12% precipitation, representing 43 and 7% of N deposition in the lake. Nitrogen deposition was highest in September due to farmlands' burning during the dry season (June–August), leading to N accumulation in the atmosphere. In conclusion, the pattern of N deposition appears to be driven by the unique climatic characteristics of the lake basin and to be closely associated with local anthropogenic activities.

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Chemotherapy is administered to a minority of hospitalized patients with diffuse large B-cell lymphoma and is associated with less likelihood of death during hospitalization

Publication date: April 2018
Source:Cancer Epidemiology, Volume 53
Author(s): Anita J. Kumar, Tobi Henzer, Angie Mae Rodday, Susan K. Parsons
BackgroundWhile treatment of DLBCL is largely outpatient, some patients require planned or unplanned admissions for chemotherapy, new diagnosis, relapse, or toxicity. We examined risk factors for receipt of inpatient chemotherapy and death during hospitalization.MethodsWe analyzed data from the 2012–2013 HCUP-NIS. We identified patient and hospital characteristics that were associated with chemotherapy administration and death.ResultsChemotherapy was given in 3260/11,150 (29.2%) of hospitalizations. Younger age, urban teaching hospitals, fewer chronic conditions, male sex, non-Medicare insurance, and "less likelihood of dying" were associated with chemotherapy. Chemotherapy portended lower odds of death; older age and longer hospitalizations were associated with increased odds of death.ConclusionWe identified socio-demographics and clinical characteristics associated with inpatient chemotherapy in DLBCL patients. Chemotherapy is associated with lower odds of death during hospitalization, suggesting that most chemotherapy is given appropriately to non-critically ill patients. Clinical acuity is a stronger predictor of death than socio-demographics.



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Exploring determinants of care-seeking behaviour of oral cancer patients in India: A qualitative content analysis

Publication date: April 2018
Source:Cancer Epidemiology, Volume 53
Author(s): Hemamalini Rath, Swikant Shah, Gaurav Sharma, Ekagrata Mishra
BackgroundA major public health concern in India is the high morbidity and mortality rates of oral cancer because of late diagnosis. Among the several determinants of this late diagnosis, the most important is the healthcare-seeking behaviour of the oral cancer patients. The aim of this study was to explore the care-seeking behaviour and its determinants among oral cancer patients.MethodsA face-to-face in-depth interview was conducted among 70 oral cancer patients using a semi-structured questionnaire, and qualitative content analysis of the results was performed.ResultsAll the patients had squamous-cell carcinoma and none had attended any screening programme. The most common site affected was the buccal mucosa with a non-healing wound. Most of the patients contacted a doctor available nearby; only 7% of patients consulted a dentist. Only one patient approached a traditional healer. The median patient delay was 30 (4–365) days and the professional delay was 40 (4–650) days. Enablers included determinants such as increasing symptoms (80%), influence of the society (74%), fear (10%), and social media (3%). The main barriers were lack of awareness (97%), hope that the lesion will heal spontaneously (90%), lack of perception of seriousness (64%), financial constraints (55%), provider switching (47%), and missed diagnosis (44%).ConclusionThe care-seeking path among oral cancer patients is complex, customised, and influenced by multiple patient-related and system-related factors.



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Effectiveness of acellular pertussis vaccine and evolution of pertussis incidence in the community of Madrid from 1998 to 2015

Publication date: Available online 10 February 2018
Source:Vaccine
Author(s): P. Latasa, L. García-Comas, A. Gil de Miguel, M.D. Barranco, I. Rodero, J.C. Sanz, M. Ordobás, A. Arce, M. Garrido-Estepa
IntroductionPertussis is a communicable disease that primarily affects infants. Vaccination has led to an important reduction in the incidence of the disease, however, resurgence of the disease has been observed. This study aimed to analyze the incidence of pertussis and assess the vaccination effectiveness (VE) of different schedules of acellular pertussis vaccination in the community of Madrid.MethodsPertussis cases notified to the Mandatory Disease Reporting System from 1998 to 2015 were analyzed. Five comparison periods were created: 1998–2001 (reference), 2002–2005, 2006–2009, 2010–2012 and 2013–2015. The incidence ratio (IR) between inter-epidemic periods was analyzed using a Poisson regression. VE was calculated using the screening method. Vaccine status data were collected from the vaccine registry.ResultsIn total, 3855 cases were notified. Inter-epidemic periods were observed every 3–4 years. The incidence increased (IR: 5.99, p < 0.05) in the 2013–2015 period, particularly among infants younger than 1 month (IR: 32.41, p < 0.05). Vaccination data were available in 89% of cases. For those receiving the last dose at ≤6-month VE was 89.9% (95% confidence interval (CI): 87.3–92.0) after one year of follow-up, and 85.5% (95% CI: 82.4–88.1) after 11 years of follow-up. For those receiving the last dose at 18-months VE decreased from 98.8% (95% CI: 98.3–99.1) to 85.1% (95% CI: 81.9–87.7) in the same period, and for those receiving the last dose at 4-year VE decreased from 99.6% (95% CI: 99.3–99.7) to 79.3% (95% CI: 74.6–83.1).ConclusionsB. pertussis is circulating in our population, as shown by the epidemic peaks and increased incidence of pertussis in recent years. VE increased with the number of doses and decreased with the follow-up period. The effect of this and other vaccination strategies must be monitored to control the disease.



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Dermaseptins as potential antirabies compounds

Publication date: Available online 10 February 2018
Source:Vaccine
Author(s): Mohamed Ben Mechlia, Afifa Belaid, Guillaume Castel, Corinne Jallet, Karen L. Mansfield, Anthony R. Fooks, Khaled Hani, Noël Tordo
Over the last 20 years, natural peptides playing a key role in defense mechanisms and innate immunity have been isolated from unicellular organisms. Amphibian skin secretes dermaseptins, 24–34 amino acids in length that have a wide antimicrobial spectrum incorporating yeast, fungi, protozoa, bacteria and enveloped viruses. The anti-rabies virus (RABV) activity of dermaseptins S3 (30aa) and S4 (28aa) from Phyllomedusa sauvagei has been investigated, and further dissected its molecular basis by comparing punctual mutation or deletion of S4 analogues. The results showed that: (1) S4 is more active than S3 against RABV infection, 89% versus 38% inhibition at 7.5 μM; (2) the 5 NH2-aa of S4 are crucial for its inhibitory potential (S46–28 lost any inhibition) but the COOH terminus stabilizes the inhibitory potential (S41–16 showed only 23% inhibition at 7.5 μM); (3) there is a correlation between viral inhibition and dermaseptin cytotoxicity, which remains however moderated for BSR cells (≤12% at 10 μM). A single mutation in position 4 (S4M4K) slightly reduced cytotoxicity while keeping its antiviral activity, 97% at 7.5 μM. S4 and S4M4K showed an antiviral activity in vitro when provided 1 h after infection. In vivo experiments in mice by intramuscular injection of non-toxic doses of dermaseptin S4M4K 1 h post-infection by a lethal dose of RABV at the same site allowed more than 50% improvement in mice survival. This study highlights the potential interest of dermaseptins as non-expansive alternatives to rabies immunoglobulins for the treatment of rabies that continues to claim about 60,000 human lives per year worldwide, almost exclusively in developing countries.



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RTS,S malaria vaccine efficacy and immunogenicity during Plasmodium falciparum challenge is associated with HLA genotype

Publication date: Available online 10 February 2018
Source:Vaccine
Author(s): C.M. Nielsen, J. Vekemans, M. Lievens, K.E. Kester, J.A. Regules, C.F. Ockenhouse
Although RTS,S remains the most advanced malaria vaccine, the factors influencing differences in vaccine immunogenicity or efficacy between individuals or populations are still poorly characterised. The analyses of genetic determinants of immunogenicity have previously been restricted by relatively small sample sizes from individual trials. Here we combine data from six Phase II RTS,S trials and evaluate the relationship between HLA allele groups and RTS,S-mediated protection in controlled human malaria infections (CHMI), using multivariate logistic or linear regression. We observed significant associations between three allele groups (HLA-A^∗01, HLA-B^∗08, and HLA-DRB1^∗15/^∗16) and protection, while another three allele groups (HLA-A^∗03, HLA-B^∗53, and HLA-DRB1^∗07) were significantly associated with lack of protection. It is noteworthy that these 'protective' allele groups are thought to be at a lower prevalence in sub-Saharan African populations than in the UK or USA where these Phase II trials occurred. Taken together, the analyses presented here give an indication that HLA genotype may influence RTS,S-mediated protective efficacy against malaria infection.



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Mass media effect on vaccines uptake during silent polio outbreak

Publication date: Available online 10 February 2018
Source:Vaccine
Author(s): Iftach Sagy, Victor Novack, Michael Gdalevich, Dan Greenberg
BackgroundDuring 2013, isolation of a wild type 1 poliovirus from routine sewage sample in Israel, led to a national OPV campaign. During this period, there was a constant cover of the outbreak by the mass media.AimsTo investigate the association of media exposure and OPV and non-OPV vaccines uptake during the 2013 silent polio outbreak in Israel.MethodsWe received data on daily immunization rates during the outbreak period from the Ministry of Health (MoH). We conducted a multivariable time trend analysis to assess the association between daily media exposure and vaccines uptake. Analysis was stratified by ethnicity and socio-economic status (SES).ResultsDuring the MoH supplemental immunization activity, 138,799 OPV vaccines were given. There was a significant association between media exposure and OPV uptake, most prominent in a lag of 3–5 days from the exposure among Jews (R.R 1.79C.I 95% 1.32–2.41) and high SES subgroups (R.R 1.71C.I 95% 1.27–2.30). These subgroups also showed increased non-OPV uptake in a lag of 3–5 days from the media exposure, in all vaccines except for MMR. Lower SES and non-Jewish subgroups did not demonstrate the same association.ConclusionOur findings expand the understanding of public behaviour during outbreaks. The public response shows high variability within specific subgroups. These findings highlight the importance of tailored communication strategies for each subgroup.



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In-depth genome analyses of viruses from vaccine-derived rabies cases and corresponding live-attenuated oral rabies vaccines

Publication date: Available online 10 February 2018
Source:Vaccine
Author(s): Florian Pfaff, Thomas Müller, Conrad M. Freuling, Christine Fehlner-Gardiner, Susan Nadin-Davis, Emmanuelle Robardet, Florence Cliquet, Vlad Vuta, Peter Hostnik, Thomas C. Mettenleiter, Martin Beer, Dirk Höper
Live-attenuated rabies virus strains such as those derived from the field isolate Street Alabama Dufferin (SAD) have been used extensively and very effectively as oral rabies vaccines for the control of fox rabies in both Europe and Canada. Although these vaccines are safe, some cases of vaccine-derived rabies have been detected during rabies surveillance accompanying these campaigns. In recent analysis it was shown that some commercial SAD vaccines consist of diverse viral populations, rather than clonal genotypes. For cases of vaccine-derived rabies, only consensus sequence data have been available to date and information concerning their population diversity was thus lacking.In our study, we used high-throughput sequencing to analyze 11 cases of vaccine-derived rabies, and compared their viral population diversity to the related oral rabies vaccines using pairwise Manhattan distances. This extensive deep sequencing analysis of vaccine-derived rabies cases observed during oral vaccination programs provided deeper insights into the effect of accidental in vivo replication of genetically diverse vaccine strains in the central nervous system of target and non-target species under field conditions. The viral population in vaccine-derived cases appeared to be clonal in contrast to their parental vaccines. The change from a state of high population diversity present in the vaccine batches to a clonal genotype in the affected animal may indicate the presence of a strong bottleneck during infection. In conclusion, it is very likely that these few cases are the consequence of host factors and not the result of the selection of a more virulent genotype. Furthermore, this type of vaccine-derived rabies leads to the selection of clonal genotypes and the selected variants were genetically very similar to potent SAD vaccines that have undergone a history of in vitro selection.



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Safety and tolerability of a liquid bovine rotavirus pentavalent vaccine (LBRV-PV) in adults

Publication date: Available online 10 February 2018
Source:Vaccine
Author(s): K. Anil, Sajjad Desai, Chetanraj Bhamare, Abhijeet Dharmadhikari, R.L. Madhusudhan, Jaya Patel, Prasad S. Kulkarni
BackgroundRotavirus Gastroenteritis (RVGE) is an important global public health problem. Recently a Lyophilized Pentavalent Human Bovine Reassortant Rotavirus vaccine (BRV-PV, Rotasiil) was licensed in India. A Liquid formulation of the same vaccine (LBRV-PV) was tested in a Phase I clinical trial.MethodsTotal 20 healthy adults were given a single oral dose of LBRV-PV and were followed for one month for safety outcomes: immediate reactions, solicited reactions, unsolicited adverse events and serious adverse events.ResultsAll 20 adults completed the study without any major protocol deviations. No immediate reaction, solicited reactions and unsolicited adverse events were reported during the study. No clinically significant changes were seen in the vital parameters and safety laboratory test results.ConclusionsLBRV-PV developed in India was safe and well tolerated in adults. Further clinical development of this vaccine in infants should be undertaken.Trial Registration – CTRI/2015/11/006,384.



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Immunization with an adjuvanted low-energy electron irradiation inactivated respiratory syncytial virus vaccine shows immunoprotective activity in mice

Publication date: Available online 10 February 2018
Source:Vaccine
Author(s): Lea Bayer, Jasmin Fertey, Sebastian Ulbert, Thomas Grunwald
Respiratory syncytial virus (RSV) is a pathogen causing severe lower respiratory tract disease in infants and the elderly. In spite of the great need for a vaccine against RSV, currently there is no licensed product on the market. A very early vaccine candidate developed in the 1960s based on formaldehyde inactivation (FI) turned out to instead enhance the disease. Our novel inactivation method applied low-energy electron irradiation (LEEI) to produce a killed RSV vaccine. LEEI yielded inactivated virus particles with a reproducible virus antigen conservation above 70%, while FI resulted in highly variable antigen conservation. Immunization of mice with LEEI-RSV elicited a strong immune response, resulting in a drastic reduction in viral load upon challenge in two independent studies. These results have implications for the development of an RSV vaccine and should be validated in further preclinical and clinical studies.



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13-Valent vaccine serotype pneumococcal community acquired pneumonia in adults in high clinical risk groups

Publication date: Available online 10 February 2018
Source:Vaccine
Author(s): Priya Daniel, Chamira Rodrigo, Thomas Bewick, Carmen Sheppard, Sonia Greenwood, Tricia M. McKeever, Caroline Trotter, Wei Shen Lim
There is debate regarding the value of vaccinating adults with the 13-valent pneumococcal conjugate vaccine (PCV-13). This analysis was conducted to investigate the risk of PCV-13 serotype community acquired pneumonia (CAP) in hospitalised adults with co-morbid disease and risk factors for pneumococcal disease in the UK.Consecutive adults hospitalised (2008–2013) with a primary diagnosis of CAP, were recruited. Pneumococcal aetiology disease was identified by use of pneumococcal urinary antigen detection and serotype identification using a validated multiplex immunoassay or serum latex agglutination. Adults with PCV-13 serotype CAP were compared to those with non-PCV-13 serotype CAP.Of 2224 patients, PCV-13 serotype CAP was identified in 337 (15.2%) and non-PCV-13 serotype CAP in 250 (11.2%) individuals. Adults aged ≥65 years with one or more clinical risk factors had a significantly lower risk of PCV-13 serotype CAP compared to those aged 16–64 years without clinical risk factors (aOR 0.61, 95%CI 0.41–0.92, p = .018). In a stacked-risk analysis, the presence of incremental clinical risk factors was associated with lower odds of PCV-13 disease (p for trend = .029) Adults with underlying chronic respiratory disease (aOR) 0.56, 95% CI 0.36–0.85, p = .007) and chronic kidney disease (aOR 0.48, 95% CI 0.25–0.92, p = .028) had significantly lower adjusted odds of PCV-13 compared to non-PCV-13 serotype CAP.This analysis suggests that in the UK, the burden of PCV13 disease is greater in adults outside the traditional 'at-risk' groups compared to adults in 'at-risk' groups.



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Incidence and epidemiology of intussusception among children under 2 years of age in Chenzhou and Kaifeng, China, 2009–2013

Publication date: Available online 10 February 2018
Source:Vaccine
Author(s): Na Liu, Catherine Yen, Tao Huang, Pengwei Cui, Jacqueline E. Tate, Baoming Jiang, Umesh D. Parashar, Zhao-jun Duan
IntroductionIn China, rotavirus is the leading cause of diarrhea hospitalizations among children aged <5 years. A locally manufactured rotavirus vaccine is available for private market use, but little is known about its coverage. Given the impending availability of newer rotavirus vaccines, we evaluated intussusception rates among children aged <2 years to better understand intussusception epidemiology for future vaccine safety monitoring.MethodsWe conducted a retrospective review at 4 hospitals in Chenzhou City of Hunan Province and Kaifeng City of Henan Province. We identified intussusception cases admitted during 2009–2013 by reviewing medical records with the ICD-10 discharge code for intussusception and extracting demographic and clinical information from the electronic clinical record systems.ResultsDuring 2009–2013, 1715 intussusception hospitalizations among 1,487,215 children aged <2 years occurred in both cities. The average annual intussusception hospitalization incidence was 112.9 per 100,000 children aged <2 years (181.8 per 100,000 children <1 year; 56 per 100,000 children 1 to <2 years). Intussusception incidence was low among infants aged <3 months and peaked at age 6–8 months. No clear seasonality was observed. Ultrasound was used to diagnose 95.9% of cases. Enema reduction was performed in 80% cases; 25% of cases in Chenzhou and 16% in Kaifeng required surgical intervention. No deaths were reported. The median time between symptom onset and admission was 1 day.ConclusionsThis study provides information on intussusception incidence and epidemiology in two cities of China during 2009–2013. Monitoring intussusception rates in this population will be important in the post-rotavirus vaccine era.



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Examination of the twinning activity in additively manufactured Ti-6Al-4V

Publication date: 15 April 2018
Source:Materials & Design, Volume 144
Author(s): H.Z. Zhong, X.Y. Zhang, S.X. Wang, J.F. Gu
This present paper investigates the dominant twinning mode and secondary twin via transmission electron microscopy at different positions of additively manufactured (AM) Ti-6Al-4V deposition wall fabricated by laser metal deposition (LMD). {10−11} 〈−1012〉 twinning system is observed as the dominant twinning mode. Secondary twins, including the inserting secondary twin and neighboring secondary twin, are characterized at position with sufficient thermal cycle history. These twinning morphologies can be rationalized to some degree from the standpoint of the twinning effect and thermal condition in additive manufacturing. This work gets insight into the twinning evolution in additively manufactured Ti alloys.

Graphical abstract

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A systematic investigation of cycle number, temperature and electric field strength effects on Si anode

Publication date: 15 April 2018
Source:Materials & Design, Volume 144
Author(s): Qihong Fang, Qiong Wang, Jia Li, Eenze Chen, Bin Liu, Pihua Wen
Cycling number, crystal orientation, temperature and electric field strength play key roles in affecting the capacity and cycling ability of Li-ion battery. However, the detailed dynamic and continuous process of capacity decline mechanism from above factors need to be further understood at nanoscale. Herein, we report deformation behavior and microstructure evolution of Si anode under electric field using molecular dynamics simulations. The results show larger cycling number and electric field strength cause larger volume expansion of Si electrode, leading to the capacity loss and the reducing cycling ability as well as the decreasing structural stability. The phase transformation from diamond cubic structure to body-centred tetragonal structure and the amorphous formation depend on lithiated and delithiated depths. The crystal orientation [100] Si anode produces the volume expansion owing to a large number of nanoscale void. The various temperatures strongly affect the number and radius of nanovoid. The associated transition in the nanovoid nucleation due to the involuntary diffusion process is driven by larger cycling number or electric field strength, resulting in the irreversible capacity loss of Li-ion battery. An established analytical model suggests that diffusion-induced stress not only relies on the position of Si anode but depends upon the cycling time.

Graphical abstract

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3D printing of Fe-based bulk metallic glass composites with combined high strength and fracture toughness

Publication date: 5 April 2018
Source:Materials & Design, Volume 143
Author(s): Ning Li, Jianji Zhang, Wei Xing, Di Ouyang, Lin Liu
Additive manufacturing is a promising technique for the production of bulk metallic glass (BMG) components without size limitations. However, the current additive manufacturing technique encounters the challenge of micro-cracking induced by huge thermal stress during the process, which significantly degrades the mechanical performance of the components. Based on systematic experiments combined with finite element simulation, we revealed that micro-cracks in inherently brittle Fe-based metallic glass during selective laser melting (SLM) are triggered by highly concentrated thermal stress around micro-pores, which is difficult to avoid during SLM even by careful process optimization. To suppress these micro-cracks, Cu and Cu-Ni alloys with high toughness as second phases were introduced to form BMG composites. The results revealed that the generation of high-density dislocations in second phases during SLM drastically reduce thermal stress by releasing strain energy and thus suppress micro-crack formation. Further investigation has shown that the introduction the second phase improves the fracture toughness of Fe-based BMGs to 47MPam^1/2, which is approximately 20 times higher than that of the Fe-based BMG (2.2MPam^1/2). Our findings provide general guidelines for the SLM fabrication of bulk metallic glass composites with tunable mechanical performances, as well as large sizes and freeform geometries.

Graphical abstract

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Three-dimensional imaging assessment of anatomic invasion and volumetric considerations for chemo/radiotherapy-based laryngeal preservation in T3 larynx cancer

Publication date: April 2018
Source:Oral Oncology, Volume 79
Author(s): Mona Kamal, Sweet Ping Ng, Salman A. Eraj, Crosby D. Rock, Brian Pham, Jay A. Messer, Adam S. Garden, William H. Morrison, Jack Phan, Steven J. Frank, Adel K. El-Naggar, Jason M. Johnson, Lawrence E. Ginsberg, Renata Ferrarotto, Jan S. Lewin, Katherine A. Hutcheson, Carlos E. Cardenas, Mark E. Zafereo, Stephen Y. Lai, Amy C. Hessel, Randal S. Weber, G. Brandon Gunn, Clifton D. Fuller, Abdallah S.R. Mohamed, David I. Rosenthal
ObjectivesTo investigate the impact of 3-Diminsional (3D) tumor volume (TV) and extent of involvement of primary tumor on treatment outcomes in a large uniform cohort of T3 laryngeal carcinoma patients treated with nonsurgical laryngeal preservation strategies.Materials and MethodsThe pretreatment contrast-enhanced computed tomography images of 90 patients with T3 laryngeal carcinoma were reviewed. Primary gross tumor volume (GTVp) was delineated to calculate the 3D TV and define the extent of invasion. Cartilage and soft tissue involvement was coded. The extent of invasion was dichotomized into non/limited invasion versus multiple invasion extension (MIE), and was subsequently correlated with survival outcomes.ResultsThe median TV was 6.6 cm³. Sixty-five patients had non/limited invasion, and 25 had MIE. Median follow-up for surviving patients was 52 months. The 5-year local control and overall survival rates for the whole cohort were 88% and 68%, respectively. There was no correlation between TV and survival outcomes. However, patients with non/limited invasion had better 5-year local control (LC) than those with MIE (95% vs 72%, p = .009) but did not have a significantly higher rate of overall survival (OS) (74% vs 67%, p = .327). In multivariate correlates of LC, MIE maintained statistical significance whereas baseline airway status showed a statistically significance trend with poor LC (p = .0087 and 0.06, respectively). Baseline good performance status was an independent predictor of improved OS (p = .03) in multivariate analysis.ConclusionThe extent of primary tumor invasion is an independent prognostic factor of LC of the disease after definitive radiotherapy in T3 larynx cancer.



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Dual-responsive polyplexes with enhanced disassembly and endosomal escape for efficient delivery of siRNA

Publication date: April 2018
Source:Biomaterials, Volume 162
Author(s): Jia Zhu, Mingxi Qiao, Qi Wang, Yuqing Ye, Shuang Ba, Jingjing Ma, Haiyang Hu, Xiuli Zhao, Dawei Chen
Despite the extracellular barriers for siRNA delivery have been overcome by utilizing advanced nanoparticle delivery systems, the key intracellular barriers after internalization including efficient disassembly of siRNA and endosomal escape still remains challenging. To address the issues, we developed a unique pH- and redox potential-responsive polyplex delivery system based on the copolymer of mPEG-b-PLA-PHis-ssPEI1.8 k, which is composed of a pH-responsive copolymer of PEG-b-PLA-PHis (Mw 5 k) and a branched PEI (Mw1.8 k) linked with redox cleavable disulfide bond. The copolymer showed excellent siRNA complexation and protection abilities against endogenous substances at the relatively low N/P ratio of 6. The siRNA release from the polyplexes (N/P 6) was markedly increased from 13.62% to 58.67% under conditions simulating the endosomal microenvironment. Fluorescence resonance energy transfer (FRET) test also indicated a higher disassembly extent of siRNA from the copolymer. The accelerated siRNA release from the polyplexes was markedly restrained when the N/P ratio was raised above 10 due to the increasing of electrostatic interactions. The efficient endosomal escape of siRNA after internalization was confirmed by confocal microscopy, which was attributed to the cleavaged PEI chains inducing membrane destabilization, the "proton sponge effect" of PHis and PEI as well as the relative small size of after disassembly. The enhanced disassembly and endosomal escape were elucidated as the leading cause for polyplexes (N/P 6) showed more efficient Bcl-2 silencing (85.45%) than those polyplexes with higher N/P ratios (N/P 10 and 15). In vivo results further demonstrated that polyplexes (N/P 6) delivery of siBcl-2 significantly inhibited the MCF-7 breast tumor growth as compared to its counterparts. The incorporation of convertible non-electrical interactions at a balance with electrostatic interactions in complexation siRNA has been demonstrated as an effective strategy to achieve efficient disassembly from stable polyplexes. Moreover, polyplexes equipped with the enhanced disassembly and endosomal escape provides a new potential way to tackle the intracellular delivery bottleneck for siRNA delivery.



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Gradient nano-engineered in situ forming composite hydrogel for osteochondral regeneration

Publication date: April 2018
Source:Biomaterials, Volume 162
Author(s): Janani Radhakrishnan, Amrutha Manigandan, Prabu Chinnaswamy, Anuradha Subramanian, Swaminathan Sethuraman
Fabrication of anisotropic osteochondral-mimetic scaffold with mineralized subchondral zone and gradient interface remains challenging. We have developed an injectable semi-interpenetrating network hydrogel construct with chondroitin sulfate nanoparticles (ChS-NPs) and nanohydroxyapatite (nHA) (∼30–90 nm) in chondral and subchondral hydrogel zones respectively. Mineralized subchondral hydrogel exhibited significantly higher osteoblast proliferation and alkaline phosphatase activity (p < 0.05). Osteochondral hydrogel exhibited interconnected porous structure and spatial variation with gradient interface of nHA and ChS–NPs. Microcomputed tomography (μCT) demonstrated nHA gradation while rheology showed predominant elastic modulus (∼930 Pa) at the interface. Co–culture of osteoblasts and chondrocytes in gradient hydrogels showed layer–specific retention of cells and cell-cell interaction at the interface. In vivo osteochondral regeneration by biphasic (nHA or ChS) and gradient (nHA + ChS) hydrogels was compared with control using rabbit osteochondral defect after 3 and 8 weeks. Complete closure of defect was observed in gradient (8 weeks) while defect remained in other groups. Histology demonstrated collagen and glycosaminoglycan deposition in neo–matrix and presence of hyaline cartilage–characteristic matrix, chondrocytes and osteoblasts. μCT showed mineralized neo–tissue formation, which was confined within the defect with higher bone mineral density in gradient (chondral: 0.42 ± 0.07 g/cc, osteal: 0.64 ± 0.08 g/cc) group. Further, biomechanical push-out studies showed significantly higher load for gradient group (378 ± 56 N) compared to others. Thus, the developed nano-engineered gradient hydrogel enhanced hyaline cartilage regeneration with subchondral bone formation and lateral host-tissue integration.



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Glucose & oxygen exhausting liposomes for combined cancer starvation and hypoxia-activated therapy

Publication date: April 2018
Source:Biomaterials, Volume 162
Author(s): Rui Zhang, Liangzhu Feng, Ziliang Dong, Li Wang, Chao Liang, Jiawen Chen, Qingxi Ma, Rui Zhang, Qian Chen, Yucai Wang, Zhuang Liu
Starvation therapy to slow down the tumor growth by cutting off its energy supply has been proposed to be an alternative therapeutic strategy for cancer treatment. Herein, glucose oxidase (GOx) is loaded into stealth liposomes and act as the glucose and oxygen elimination agent to trigger the conversion of glucose and oxygen into gluconic acid and H2O2. Such liposome-GOx after intravenous injection with effective tumor retention is able to exhaust glucose and oxygen within the tumor, producing cytotoxic H2O2 and enhancing hypoxia, as vividly visualized by non-invasive in vivo photoacoustic imaging. By further combination treatment with stealth liposomes loaded with banoxantrone dihydrochloride (AQ4N), a hypoxia-activated pro-drug, a synergistically enhanced tumor growth inhibition effect is achieved in the mouse model of 4T1 tumor. Hence, by combining starvation therapy and hypoxia-activated therapy tactfully utilizing liposomal nanocarriers to co-deliver both enzymes and prodrugs, an innovative strategy is presented in this study for effective cancer treatment.



http://ift.tt/2ExQ90E

Influence of heading perception in the control of posture

Publication date: Available online 10 February 2018
Source:Journal of Electromyography and Kinesiology
Author(s): Alessandro Piras, Milena Raffi, Monica Perazzolo, Salvatore Squatrito
The optic flow visual input directly influences the postural control. The aim of the present study was to examine the relationship between visually induced heading perception and postural stability, using optic flow stimulation. The dots were accelerated to simulate a heading direction to the left or to the right of the vertical midline. The participants were instructed to indicate the perceived optic flow direction by making a saccade to the simulated heading direction. We simultaneously acquired electromyographyc and center of pressure (COP) signals. We analysed the postural sway during three different epochs: i) the first 500 ms after the stimulus onset, ii) 500 ms before saccade onset, epoch in which the perception is achieved and, iii) 500 ms after saccade onset. Participants exhibited a greater postural instability before the saccade, when the perception of heading was achieved, and the sway increased further after the saccade. These results indicate that the conscious representation of the self-motion affects the neural control of posture more than the mere visual motion, producing more instability when visual signals are contrasting with eye movements. It could be that part of these effects are due to the interactions between gaze shift and optic flow.



http://ift.tt/2C96KCF

Axillary motor nerve conduction study: description of technique and provision of normative data

Publication date: Available online 10 February 2018
Source:Journal of Electromyography and Kinesiology
Author(s): Panagiotis Zis, Marios Hadjivassiliou, Dasappaiah Ganesh Rao
BackgroundAxillary nerve lesions can commonly occur secondary to trauma or brachial plexopathy. Our aim was to describe our technique of axillary nerve motor conduction studies and provide the respective normal values.MethodsActive electrode was positioned over the most prominent portion of the middle deltoid, approximately 5-7cm distal to the acromion. Reference electrode was positioned over the acromion. Ground electrode was placed between the active and the reference electrodes. Supramaximal stimulation was at the Erb's point.ResultsA total of 154 participants (61% male, age range 18-84) were included. There was a significant positive correlation between the subjects' age and the onset latency Spearman's rho 0.312, p<0.001) and a significant negative correlation between the participants' age and the CMAP (Spearman's rho -0.481, p<0.001).For the total male population the lower normal value for the CMAP was 7.6mV and the higher normal value for the onset latency was 5.0msec. For the total female population the respective normal values were 6.5mV and 3.5msec.In order to detect an axillary nerve lesion, asymmetry of >40% in the CMAPS between the symptomatic and the asymptomatic side show a sensitivity of 95.2% and a specificity of 96.6%.ConclusionWe described our technique of axillary nerve motor conduction studies and provided the respective normal values stratified for age and gender. When suspecting an axillary nerve lesion it is always worth performing axillary motor NCS bilaterally and compare the CMAPs.



http://ift.tt/2Eh3v21

A dual tracer ratio method for comparative emission measurements in an experimental dairy housing

Publication date: April 2018
Source:Atmospheric Environment, Volume 179
Author(s): Joachim Mohn, Kerstin Zeyer, Margret Keck, Markus Keller, Michael Zähner, Jernej Poteko, Lukas Emmenegger, Sabine Schrade
Agriculture, and in particular dairy farming, is an important source of ammonia (NH3) and non-carbon dioxide greenhouse gas (GHG) emissions. This calls for the development and quantification of effective mitigation strategies. Our study presents the implementation of a dual tracer ratio method in a novel experimental dairy housing with two identical, but spatially separated housing areas. Modular design and flexible floor elements allow the assessment of structural, process engineering and organisational abatement measures at practical scale. Thereby, the emission reduction potential of specific abatement measures can be quantified in relation to a reference system. Emissions in the naturally ventilated housing are determined by continuous dosing of two artificial tracers (sulphur hexafluoride SF6, trifluoromethylsulphur pentafluoride SF5CF3) and their real-time detection in the ppt range with an optimized GC-ECD method. The two tracers are dosed into different experimental sections, which enables the independent assessment of both housing areas. Mass flow emissions of NH3 and GHGs are quantified by areal dosing of tracer gases and multipoint sampling as well as real-time analysis of both tracer and target gases. Validation experiments demonstrate that the technique is suitable for both areal and point emission sources and achieves an uncertainty of less than 10% for the mass emissions of NH3, methane (CH4) and carbon dioxide (CO2), which is superior to other currently available methods. Comparative emission measurements in this experimental dairy housing will provide reliable, currently unavailable information on emissions for Swiss dairy farming and demonstrate the reduction potential of mitigation measures for NH3, GHGs and potentially other pollutants.

Graphical abstract

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Summertime diurnal variations in the isotopic composition of atmospheric nitrogen dioxide at a small midwestern United States city

Publication date: April 2018
Source:Atmospheric Environment, Volume 179
Author(s): Wendell W. Walters, Huan Fang, Greg Michalski
The nitrogen and oxygen stable isotopes (δ¹⁵N & δ¹⁸O) of nitrogen oxides (NOx = nitric oxide (NO) + nitrogen dioxide (NO2)) may be a useful tool for partitioning NOx emission sources and for evaluating NOx photochemical cycling, but few measurements of in situ NOx exist. In this study, we have collected and characterized the diurnal variability in δ¹⁵N and δ¹⁸O of NO2 from ambient air at a small Midwestern city (West Lafayette, IN, USA, 40.426° N, 86.908° W) between July 7 to August 5, 2016, using an active sampling technique. Large variations were observed in both δ¹⁵N(NO2) and δ¹⁸O(NO2) that ranged from −31.4 to 0.4‰ and 41.5–112.5‰, respectively. Daytime averages were −9.2 ± 5.7‰ (x̅ ± 1σ) and 86.5 ± 14.1‰ (n = 11), while nighttime averages were −13.4 ± 7.3‰ and 56.3 ± 7.1‰ (n = 12) for δ¹⁵N(NO2) and δ¹⁸O(NO2), respectively. The large variability observed in δ¹⁵N(NO2) is predicted to be driven by changing contributions of local NOx emission sources, as calculated isotope effects predict a minor impact on δ¹⁵N(NO2) relative to δ¹⁵N(NOx) that is generally less than 2.5‰ under the sample collection conditions of high ozone concentration ([O3]) relative to [NOx]. A statistical δ¹⁵N mass-balance model suggests that traffic-derived NOx is the main contributor to the sampling site (0.52 ± 0.22) with higher relative contribution during the daytime (0.58 ± 0.19) likely due to higher traffic volume than during the nighttime (0.47 ± 0.22). The diurnal cycle observed in δ¹⁸O(NO2) is hypothesized to be a result of the photochemical cycling of NOx that elevates δ¹⁸O(NO2) during the daytime relative to the nighttime. Overall, this data suggests the potential to use δ¹⁵N(NO2) for NOx source partitioning under environmental conditions of high [O3] relative to [NOx] and δ¹⁸O(NO2) for evaluating VOC-NOx-O3 chemistry.



http://ift.tt/2BT3pMB

Three-dimensional imaging assessment of anatomic invasion and volumetric considerations for chemo/radiotherapy-based laryngeal preservation in T3 larynx cancer

Publication date: April 2018
Source:Oral Oncology, Volume 79
Author(s): Mona Kamal, Sweet Ping Ng, Salman A. Eraj, Crosby D. Rock, Brian Pham, Jay A. Messer, Adam S. Garden, William H. Morrison, Jack Phan, Steven J. Frank, Adel K. El-Naggar, Jason M. Johnson, Lawrence E. Ginsberg, Renata Ferrarotto, Jan S. Lewin, Katherine A. Hutcheson, Carlos E. Cardenas, Mark E. Zafereo, Stephen Y. Lai, Amy C. Hessel, Randal S. Weber, G. Brandon Gunn, Clifton D. Fuller, Abdallah S.R. Mohamed, David I. Rosenthal
ObjectivesTo investigate the impact of 3-Diminsional (3D) tumor volume (TV) and extent of involvement of primary tumor on treatment outcomes in a large uniform cohort of T3 laryngeal carcinoma patients treated with nonsurgical laryngeal preservation strategies.Materials and MethodsThe pretreatment contrast-enhanced computed tomography images of 90 patients with T3 laryngeal carcinoma were reviewed. Primary gross tumor volume (GTVp) was delineated to calculate the 3D TV and define the extent of invasion. Cartilage and soft tissue involvement was coded. The extent of invasion was dichotomized into non/limited invasion versus multiple invasion extension (MIE), and was subsequently correlated with survival outcomes.ResultsThe median TV was 6.6 cm³. Sixty-five patients had non/limited invasion, and 25 had MIE. Median follow-up for surviving patients was 52 months. The 5-year local control and overall survival rates for the whole cohort were 88% and 68%, respectively. There was no correlation between TV and survival outcomes. However, patients with non/limited invasion had better 5-year local control (LC) than those with MIE (95% vs 72%, p = .009) but did not have a significantly higher rate of overall survival (OS) (74% vs 67%, p = .327). In multivariate correlates of LC, MIE maintained statistical significance whereas baseline airway status showed a statistically significance trend with poor LC (p = .0087 and 0.06, respectively). Baseline good performance status was an independent predictor of improved OS (p = .03) in multivariate analysis.ConclusionThe extent of primary tumor invasion is an independent prognostic factor of LC of the disease after definitive radiotherapy in T3 larynx cancer.



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Comments on “Compositional and functional variations of oral microbiota associated with the mutational changes in oral cancer” by Yang et al.

Publication date: Available online 10 February 2018
Source:Oral Oncology
Author(s): Divya Gopinath, Rohit Kunnath Menon




http://ift.tt/2BPWAv3

Closed-Eye Visualizations in the Setting of Hyponatremia

Purpose. To report a case of closed-eye visualizations and to clarify the different types of hallucinations and their etiologies. Methods. Retrospective case report of a patient with closed-eye visualizations secondary to hyponatremia. Clinical findings, physical exam, laboratory assessment, treatment, and disease course from the patient's hospitalization were used in creating this report. Follow-up data after discharge were also obtained. Results. Closed-eye visualizations were diagnosed as secondary to hyponatremia, as they did not occur with the eyes open, and potential alternate causes were excluded. Serum sodium nadir was 119 mEq/L. Symptoms resolved with correction of hyponatremia via fluid resuscitation and electrolyte replenishment. There has been no recurrence of the symptoms. Conclusion. This patient had hallucinations exclusively with the eyes closed, which must be differentiated from the release hallucinations seen with the eyes open in Charles Bonnet syndrome. This patient had no visual loss or retinal disease, which should be suspected in open eye hallucinations.

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Vitamin D3 signaling and breast cancer: Insights from transgenic mouse models

Publication date: Available online 10 February 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Lei Sheng, David F. Callen, Andrew G. Turner
The biologically active form of vitamin D3 (1,25(OH)2D) regulates epithelial cell differentiation, proliferation, and apoptosis, lending weight to clinical evidence linking vitamin D3 insufficiency to breast cancer incidence and mortality. Local dysregulation of vitamin D3metabolism has been identified in patients with breast cancer, implying that disruption of 1,25(OH)2D signaling may contribute to breast cancer development in an autocrine or paracrine manner. Mouse mammary glands express the critical enzymes responsible for 1,25(OH)2D synthesis (Cyp2r1 and Cyp27b1), degradation (Cyp24a1), as well as the vitamin D3 receptor (Vdr), and genetically modified mouse models have revealed a great deal about the role of vitamin D3 in cancer initiation and progression. Ablation of Vdr or Cyp27b1 in murine models of mammary cancer reduces the anti-tumor effects of vitamin D3, while elevation of Cyp24a1 levels increases degradation of 1,25(OH)2D, leading to diminished anti-tumor effects. This review discusses the recent transgenic mouse models of vitamin D3 metabolism and the Vdr signaling network, and how these contribute to mammary gland development, and cancer tumorigenesis and progression. Collectively, these mouse models have helped clarify mechanisms of action of the vitamin D3 signaling and suggest that activation or restoration of the vitamin D3 regulated pathway is a potential approach for human breast cancer prevention.



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Discovery and Development of ODM-204: A Novel Nonsteroidal Compound for the Treatment of Castration-Resistant Prostate Cancer by blocking the Androgen Receptor and Inhibiting CYP17A1

Publication date: Available online 10 February 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Riikka Oksala, Anu Moilanen, Reetta Riikonen, Petteri Rummakko, Arja Karjalainen, Mikko Passiniemi, Gerd Wohlfahrt, Päivi Taavitsainen, Chira Malmström, Meri Ramela, Hanna-Maija Metsänkylä, Riikka Huhtaniemi, Pekka J. Kallio, Mika VJ. Mustonen
We report the discovery of a novel nonsteroidal dual-action compound, ODM-204, that holds promise for treating patients with castration-resistant prostate cancer (CRPC), an advanced form of prostate cancer characterised by high androgen receptor (AR) expression and persistent activation of the AR signaling axis by residual tissue androgens. For ODM-204, has a dual mechanism of action. The compound is anticipated to efficiently dampen androgenic stimuli in the body by inhibiting CYP17A1, the prerequisite enzyme for the formation of dihydrotestosterone (DHT) and testosterone (T), and by blocking AR with high affinity and specificity. In our study, ODM-204 inhibited the proliferation of androgen-dependent VCaP and LNCaP cells in vitro and reduced significantly tumour growth in a murine VCaP xenograft model in vivo. Intriguingly, after a single oral dose of 10-30 mg/kg, ODM-204 dose-dependently inhibited adrenal and testicular steroid production in sexually mature male cynomolgus monkeys. Similar results were obtained in human chorionic gonadotropin-treated male rats. In rats, leuprolide acetate-mediated (LHRH agonist) suppression of the circulating testosterone levels and decrease in weights of androgen-sensitive organs was significantly and dose-dependently potentiated by the co-administration of ODM-204. ODM-204 was well tolerated in both rodents and primates. Based on our data, ODM-204 could provide an effective therapeutic option for men with CRPC.



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Food insecurity, diet quality and body mass index of women participating in the Supplemental Nutrition Assistance Program: The role of intrapersonal, home environment, community and social factors

Publication date: 1 June 2018
Source:Appetite, Volume 125
Author(s): Namrata Sanjeevi, Jeanne Freeland-Graves, Matthew Hersh
Obesity is a public health problem that disproportionately affects low-income populations. Moreover, participation in Supplemental Nutrition Assistance Program (SNAP) has been associated with obesity among low-income women. The goal of this study was to determine the impact of intrapersonal, home environment, community and social factors on diet quality and body mass index (BMI) of low-income women participating in SNAP. This study also aimed to examine the role of these factors in mediating the relationship between food insecurity and diet quality, and BMI. A total of 152 women receiving SNAP benefits were recruited from low-income neighborhood centers and housing communities, and administered a demographics questionnaire, the United States adult food security scale, food frequency questionnaire, and multi-dimensional home environment scale (MHES). They also were measured for height and weight to calculate BMI. The Dietary Guidelines Adherence Index 2015 was used to measure diet quality. Regression analyses were conducted to determine the MHES subscales that were significant predictors of diet quality and BMI. The Preacher and Hayes mediation model was used to evaluate the mediation of the relationship between food insecurity and diet quality, and BMI by the MHES. Emotional eating resistance and favorable social eating behaviors were positively associated with diet quality; whereas emotional eating resistance, lower availability of unhealthy food at home, neighborhood safety and favorable social eating behaviors were inversely associated with BMI in women participating in SNAP. The MHES significantly mediated the relationship between food insecurity and BMI. These results emphasize the importance of intrapersonal, home environment, community and social factors in mediating the relationship between food insecurity and BMI in low-income women.



http://ift.tt/2G4BHKy

Effects of sewage sludge modified by coal gasification slag and electron beam irradiation on the growth of Alhagi sparsifolia Shap. and transfer of heavy metals

Abstract

A greenhouse experiment was performed to investigate the feasibility of sewage sludge modified by coal gasification slag pretreatment and electron beam irradiation in soil application for cultivation of Alhagi sparsifolia Shap. The results showed that modified sewage sludge had an active effect on the growth of Alhagi sparsifolia Shap. The sandy soil and modified sludge at the volume ratio of 2:1 were optimal, and the growth potential of Alhagi sparsifolia Shap. was highest. In the sandy soil, the values of bioconcentration factor of most heavy metals were below 1.0 except for Zn and Cu. The average bioconcentration factor values of heavy metals in Alhagi sparsifolia Shap. decreased in a sequence of Zn>Cu>Ni> Mn>Co>Pb>Cr>Fe>V>Cd>Mo for all treatments. Alhagi sparsifolia Shap. could decrease the eco-toxicity and bioavailability of Ni, Fe, and Mo in all mixed soil, and Alhagi sparsifolia Shap. could reduce the eco-toxicity and bioavailability of all heavy metals discussed in this study (except for Mn) in the mixed soil of SS:MSS = 2:1.

http://ift.tt/2ExnetH

Diagnosis and Management of Pemphigus: recommendations by an International Panel of Experts

Several European countries recently developed international diagnostic and management guidelines for pemphigus, which have been instrumental in the standardization of pemphigus management,

http://ift.tt/2EUmGfj

Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib: a 32-week open label extension study with optional narrow-band ultraviolet B

http://ift.tt/2EUiZGl

Global Burden of Urticaria: Insights from the 2016 Global Burden of Disease Study

http://ift.tt/2Eg4uvl

Whole-exome sequencing reveals differences between nail apparatus melanoma and acral melanoma

http://ift.tt/2EVnlgu

The staining of clothing by sunscreens: a pilot study

http://ift.tt/2EgRBBk

Rapid improvement of prurigo nodularis with cyclosporine treatment

http://ift.tt/2Edbk4H

Rethinking Biotin Therapy for Hair, Nail, and Skin Disorders

http://ift.tt/2EiVHJ0

Commentary: Skin cancer in the military

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A technique for more precise distinction between catagen and telogen human hair follicles ex-vivo

http://ift.tt/2Ehc49b

In-office compounding of lidocaine-epinephrine: an option for anesthesia preparation prior to skin biopsy

http://ift.tt/2EVTHaV

The impact of underlying disease state on outcomes in patients with pyoderma gangrenosum: A national survey

It is unclear if the underlying disease affects the outcomes in pyoderma gangrenosum.

http://ift.tt/2EhWudt

Comparative Effectiveness of Targeted Immunomodulators for the Treatment of Moderate-to-Severe Plaque Psoriasis: A Systematic Review and Network Meta-Analysis

The comparative effectiveness of available targeted immunomodulators for moderate-to-severe psoriasis has not been evaluated.

http://ift.tt/2EVKwaz

Role of residence time on the transformation of Zn, Cu, Pb and Cd attached to road dust in different land uses

Publication date: 30 May 2018
Source:Ecotoxicology and Environmental Safety, Volume 153
Author(s): Ayomi Jayarathne, Prasanna Egodawatta, Godwin A. Ayoko, Ashantha Goonetilleke
The adsorption behaviour of metals deposited on road surfaces undergo changes during dry weather periods, with the bioavailability varying compared to the original species, prior to incorporation in stormwater runoff. This study investigated the role of antecedent dry days on the transformation characteristics of Zn, Cu, Pb and Cd attached to different geochemical forms of road dust, in order to predict potential stormwater quality impacts. The study outcomes showed that the exchangeable fraction generally decreased with the increase in antecedent dry days, but the reducible, oxidisable and residual fractions increased. This implies that there is a time-dependent transformation of weakly bound metals in road dust to more persistent chemical forms. The transformation rate of metals was found to be in the order of Pb > Cu > Zn > Cd. Significant changes in metal distribution among the geochemical fractions were observed up to seven dry days, suggesting that during the initial antecedent dry days, the transformations can be relatively more significant. Among the analysed metals, Cd present on road surfaces has a higher potential for being bioavailable during the antecedent dry days.

Graphical abstract

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Signaling pathways regulating pituitary functions

Publication date: 5 March 2018
Source:Molecular and Cellular Endocrinology, Volume 463
Author(s): Stanko S. Stojilkovic




http://ift.tt/2G0t04b

Editorial Board

Publication date: 5 March 2018
Source:Molecular and Cellular Endocrinology, Volume 463





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Low CD25 on autoreactive Tregs impairs tolerance via low dose IL-2 and antigen delivery

Publication date: Available online 10 February 2018
Source:Journal of Autoimmunity
Author(s): Chie Hotta-Iwamura, Charles Benck, William D. Coley, Yi Liu, Yongge Zhao, Juan A. Quiel, Kristin V. Tarbell
Dendritic cell (DC)-mediated T cell tolerance deficiencies contribute to the pathogenesis of autoimmune diseases such as type 1 diabetes. Delivering self-antigen to dendritic-cell inhibitory receptor-2 (DCIR2)⁺ DCs can delay but not completely block diabetes development in NOD mice. These DCIR2-targeting antibodies induce tolerance via deletion and anergy, but do not increase islet-specific Tregs. Because low-dose IL-2 (LD-IL-2) administration can preferentially expand Tregs, we tested whether delivering islet-antigen to tolerogenic DCIR2⁺ DCs along with LD-IL-2 would boost islet-specific Tregs and further block autoimmunity. But, surprisingly, adding LD-IL-2 did not increase efficacy of DC-targeted antigen to inhibit diabetes. Here we show the effects of LD-IL-2, with or without antigen delivery to DCIR2⁺ DCs, on both polyclonal and autoreactive Treg and conventional T cells (Tconv). As expected, LD-IL-2 increased total Tregs, but autoreactive Tregs required both antigen and IL-2 stimulation for optimal expansion. Also, islet-specific Tregs had lower CD25 expression and IL-2 sensitivity, while islet-specific Tconv had higher CD25 expression, compared to polyclonal populations. LD-IL-2 increased activation and expansion of Tconv, and was more pronounced for autoreactive cells after treatment with IL-2 + islet-antigen. Therefore, LD-IL-2 therapy, especially when combined with antigen stimulation, may not optimally activate and expand antigen-specific Tregs in chronic autoimmune settings.



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Control of B-1a cell development by instructive BCR signaling

Taras Kreslavsky | Jason B Wong | Maria Fischer | Jane A Skok | Meinrad Busslinger

http://ift.tt/2EyVvsD

The regulation of lymphocyte activation and proliferation

Susanne Heinzel | Julia M Marchingo | Miles B Horton | Philip D Hodgkin

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Natural killer cell education in human health and disease

Jeanette E Boudreau | Katharine C Hsu

http://ift.tt/2G3hzsD

Inhibition of non-homologous end joining in Fanconi Anemia cells results in rescue of survival after interstrand crosslinks but sensitization to replication associated double-strand breaks

Publication date: Available online 10 February 2018
Source:DNA Repair
Author(s): Laura J. Eccles, Andrew C. Bell, Simon N. Powell
When Fanconi Anemia (FA) proteins were depleted in human U2OS cells with integrated DNA repair reporters, we observed decreases in homologous recombination (HR), decreases in mutagenic non-homologous end joining (m-NHEJ) and increases in canonical NHEJ, which was independently confirmed by measuring V(D)J recombination. Furthermore, depletion of FA proteins resulted in reduced HR protein foci and increased NHEJ protein recruitment to replication-associated DSBs, consistent with our observation that the use of canonical NHEJ increases after depletion of FA proteins in cycling cells. FA-depleted cells and FA-mutant cells were exquisitely sensitive to a DNA-PKcs inhibitor (DNA-PKi) after sustaining replication-associated double strand breaks (DSBs). By contrast, after DNA interstrand crosslinks, DNA-PKi resulted in increased survival in FA-deficient cells, implying that NHEJ is contributing to lethality after crosslink repair. Our results suggest FA proteins inhibit NHEJ, since repair intermediates from crosslinks are rendered lethal by NHEJ. The implication is that bone marrow failure in FA could be triggered by naturally occurring DNA crosslinks, and DNA-PK inhibitors would be protective. Since some sporadic cancers have been shown to have deficiencies in the FA-pathway, these tumors should be vulnerable to NHEJ inhibitors with replication stress, but not with crosslinking agents, which could be tested in future clinical trials.



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Sporadic pediatric papillary thyroid carcinoma harboring the ETV6/NTRK3 fusion oncogene in a 7-year-old Japanese girl: a case report and review of literature

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Ectopic impulse generation in peripheral nerve hyperexcitability syndromes and amyotrophic lateral sclerosis

Publication date: Available online 10 February 2018
Source:Clinical Neurophysiology
Author(s): Yu-ichi Noto, Neil G. Simon, Alexis Selby, Nidhi Garg, Kazumoto Shibuya, Nortina Shahrizaila, William Huynh, José M. Matamala, Thanuja Dharmadasa, Susanna B. Park, Steve Vucic, Matthew C. Kiernan
ObjectiveTo elucidate differences in the distribution and firing frequency of fasciculations between peripheral nerve hyperexcitability syndromes and amyotrophic lateral sclerosis (ALS) and to explore the generator site of fasciculations.MethodsUltrasound of 14 preselected muscles was performed in patients with peripheral hyperexcitability and ALS. The distribution and firing frequency of fasciculations were calculated. Cortical excitability assessment was also done by threshold tracking transcranial magnetic stimulation.ResultsIn total, 518 muscles from 37 peripheral hyperexcitability patients and 756 muscles from 54 ALS patients were examined. Regarding the detection rate, 74% of muscles in ALS patients demonstrated fasciculations, compared with 34% of muscles in peripheral hyperexcitability patients (P <0.001). The number of unique repeating focal muscle fasciculation movements per muscle and firing frequency of individual fasciculations in ALS were both significantly higher than those in peripheral hyperexcitability (P <0.001). Furthermore, cortical silent period duration negatively correlated with the number and firing frequency of fasciculations in ALS (P <0.05). A similar relationship was not evident in peripheral hyperexcitability.ConclusionsALS patients exhibited a widespread distribution of fasciculations, whereas peripheral hyperexcitability patients had a lower limb-dominant pattern.SignificanceA significant proportion of fasciculations in ALS may be influenced by changes in central excitability.



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Reply to “10-10 Electrode System for EEG Recording”

Publication date: Available online 10 February 2018
Source:Clinical Neurophysiology
Author(s): Margitta Seeck, Thomas Bast, Frans Leijten, Bin He, Sándor Beniczky




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Cochlear implantation in children with auditory neuropathy spectrum disorder: A multicenter study on auditory performance and speech production outcomes

Publication date: Available online 7 February 2018
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Ahmad Daneshi, Marjan Mirsalehi, Seyed Basir Hashemi, Mohammad Ajalloueyan, Mohsen Rajati, Mohammad Mahdi Ghasemi, Hesamaldin Emamdjomeh, Alimohamad Asghari, Shabahang Mohammadi, Mohammad Mohseni, Saleh Mohebbi, Mohammad Farhadi
ObjectivesTo evaluate the auditory performance and speech production outcome in children with auditory neuropathy spectrum disorder (ANSD). The effect of age on the outcomes of the surgery at the time of implantation was also evaluated.MethodsCochlear implantation was performed in 136 children with bilateral severe-to- profound hearing loss due to ANSD, at four tertiary academic centers. The patients were divided into two groups based on the age at the time of implantation; Group I: Children ≤24 months, and Group II: subjects >24 months. The categories of auditory performance (CAP) and speech intelligibility rating (SIR) scores were evaluated after the first and second years of implantation. The differences between the CAP and SIR scores in the two groups were assessed.ResultsThe median CAP scores improved significantly after the cochlear implantation in all the patients (p value < 0.001). The improvement in the CAP scores during the first year in Group II was greater than Group I (p value: 0.007), but the improvement in CAP scores tended to be significantly higher in patients who were implanted at ≤24 months (p value < 0.001). There was no significant difference between two groups in SIR scores at first-year and second-year follow-ups. The evaluation of the SIR improvement revealed significantly higher values for Group I during the second-year follow-up (p value: 0.003).ConclusionThe auditory performance and speech production skills of the children with ANSD improved significantly after cochlear implantation, and this improvement was affected by age at the time of implantation.



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Treatment of extensive post tonsillectomy oropharyngeal stenosis secondary to fibromatosis

Publication date: Available online 2 February 2018
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Brian Chang, Jennifer F. Ha, David Zopf
Aggressive fibromatosis is an uncommon, benign tumor of fibroblastic origin with high potential for local invasion. Less than a quarter of these lesions are located in the head and neck, and although extremely rare, associations have been demonstrated with physical trauma. We describe a unique case of oropharyngeal fibromatosis with traumaticetiology, managed successfully with surgical excision of the lesion with negative surgical margins. A 5-year old patient was found to have an aggressive fibromatosis causing oropharyngeal stenosis following tonsillectomy. We demonstrate that surgical resection with a clear margin allowed for alleviation of stenosis without recurrences reported since the procedure.



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Volume relationships between cricoid and main stem bronchi in children using three-dimensional computed tomography imaging

Publication date: Available online 5 February 2018
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Tariq M. Wani, Ayman Mohammad AlAhdal, Mohammed Hakim, Tanveer Hussein, Abdul Basit Mir, Ravees Jan, Dmitry Tumin, Joseph D. Tobias
BackgroundThere are limited data to guide the selection of the appropriate sized endobronchial tube for main stem intubation to provide one-lung ventilation in children. The relationship between the cricoid and the main bronchi (right and left) has been previously evaluated using two-dimensional computed tomography (CT) imaging and video-bronchoscopic images. The present study defines the three-dimensional, CT-derived volume-based relationships between the right main-stem bronchus (RMB), left main-stem bronchus (LMB), and the cricoid ring.MethodsThe three-dimensional CT images of 35 children, less than 8 years of age, undergoing radiological evaluation unrelated to airway or mediastinal symptomatology were examined. The images of the airway column were evaluated at the level of the cricoid and main stem bronchi (right and left). Volumes were calculated and comparisons made between these levels.ResultsThere was no statistically significant difference based on gender for the cricoid and main stem bronchi volumes. A statistically significant difference was observed between the cricoid and left main stem bronchi volumes as well as between the right and left main stem bronchi.ConclusionThe relationship (ratio) between the volumes of the cricoid and main stem bronchi remains constant by age. The cricoid dimensions can be used to predict the main stem bronchi dimensions.



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Bony cochlear nerve canal stenosis in pediatric unilateral sensorineural hearing loss

Publication date: March 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 106
Author(s): Chae-Hyun Lim, Ji Hyung Lim, Doyoun Kim, Ho sung Choi, Dong-Hee Lee, Dong-Kee Kim
ObjectivesThis study was performed to evaluate the frequency of bony cochlear nerve canal (BCNC) stenosis and its clinical significance in pediatric patients with unilateral sensorineural hearing loss (SNHL) of unknown etiology.Materials and methodsWe analyzed the medical records and temporal bone computed tomography (CT) results of patients less than 13 years of age with a diagnosis of unilateral SNHL of unknown etiology between July 2007 and July 2017. We compared the BCNC diameter between both sides and analyzed the age at diagnosis, degree of hearing loss, and accompanying inner ear anomalies.ResultsIn 42 patients, the mean age at diagnosis was 7.4 ± 3.6 years, and the average hearing level in the affected ear was 87.9 ± 20.0 dB HL (decibels hearing level). The average diameter of the BCNC was 1.22 ± 0.75 mm on the affected side and 1.96 ± 0.52 mm on the normal side. The most suitable criterion for BCNC stenosis appeared to be a diameter of 1.2 mm by the recursive partitioning procedure. With application of this criterion, the rate of BCNC stenosis was significantly greater on the affected side than on the normal side (52.4% vs. 4.8%, respectively; P < 0.05). A narrow internal acoustic canal was found in two patients, and vestibular and cochlear anomalies were found in three patients each.ConclusionsOur results suggest that it is reasonable to set a diameter of 1.2 mm as a cutoff for BCNC stenosis, and also that BCNC stenosis is a common cause of unilateral SNHL of unknown etiology in childhood.



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Healthcare and psychosocial experiences of individuals with craniofacial microsomia: Patient and caregivers perspectives

Publication date: Available online 7 February 2018
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Daniela V. Luquetti, Michelle R. Brajcich, Nicola M. Stock, Carrie L. Heike, Alexis L. Johns
ObjectiveCraniofacial microsomia (CFM) is primarily characterized by underdevelopment of the ear and mandible, with several additional possible congenital anomalies. Despite the potential burden of care and impact of CFM on multiple domains of functioning, few studies have investigated patient and caregiver perspectives. The objective of this study was to explore the diagnostic, treatment-related, and early psychosocial experiences of families with CFM with the aim of optimizing future healthcare delivery.MethodsForty-two caregivers and nine adults with CFM responded to an online mixed-methods survey. Descriptive statistics and qualitative methods were used for the analysis.ResultsSurvey respondents reported high rates of subspecialty evaluations, surgeries, and participation in therapies. Some participants reported receiving inaccurate or incomplete information about CFM and experienced confusion about etiology. Communication about CFM among family members included mostly positive messages. Self-awareness of facial differences began at a mean age of three years and teasing at mean age six, with 43% of individuals four years or older reporting teasing. Teasing often involved name-calling and frequent reactions were ignoring and negative emotional responses. Participants ranked "understanding diagnosis and treatment" as a top priority for future research and had the most questions about etiology and treatment guidance.ConclusionsThe survey results on the healthcare and psychosocial experiences from birth through adulthood of individuals with CFM reinforce the need for ongoing psychological assessment and intervention. Healthcare provision could be improved through establishing diagnostic criteria and standardized treatment guidelines, as well as continued investigation of CFM etiology.



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Challenges and outcomes of cholesteatoma management in children with Down syndrome

Publication date: March 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 106
Author(s): Saied Ghadersohi, Bharat Bhushan, Kathleen R. Billings
IntroductionThe high incidence of chronic otitis media with effusion and Eustachian tube dysfunction in children with Down syndrome (DS) may predispose them to cholesteatoma formation. Establishing the diagnosis, choosing the appropriate operative intervention, and post-operative care can be challenging.ObjectiveTo describe management strategies for cholesteatoma diagnosis, surgical treatment, and post-operative management in children with Down syndrome.MethodsRetrospective case series of 14 patients (17 total ears) with Down syndrome diagnosed with cholesteatoma over a 9-year period.ResultsA total of 14 patients with cholesteatoma (3 with bilateral disease) were analyzed. Thirteen ears (76.5%) had ≥2 tympanostomy tubes insertions prior to cholesteatoma diagnosis, and otorrhea and hearing loss were the most common presenting symptoms. Common pre-operative CT scan findings included mastoid sclerosis and ossicular erosion. The average age at first surgery was 9.8 years, and the average follow-up was 4.3 years. For acquired cholesteatoma, most ears were managed with canal wall up (CWU) approaches, but ultimately 6/15 (40.0%) required canal wall down (CWD) approaches. Postoperatively, 3 (20.0%) ears developed new tympanic membrane retraction pockets, but no recurrent cholesteatoma. Four (26.7%) ears developed recurrent disease, and 3 (20.0%) had residual disease at secondary procedures. Ossiculoplasty was performed in 4 ears. Twelve (70.6%) ears were rehabilitated with hearing aids or FM systems.ConclusionsThe diagnosis of cholesteatoma in Down syndrome was associated with otorrhea, hearing loss, and CT scan findings of ossicular erosion and mastoid sclerosis. Most cases were managed with CWU surgical approaches. Hearing aid use was common post-operatively.



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Tracheal paraganglioma presenting as stridor in a pediatric patient, case report and literature review

Publication date: Available online 7 February 2018
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Amy L. Dimachkieh, Allison Dobbie, Damon R. Olson, Mark A. Lovell, Jeremy D. Prager
ObjectiveTo review tracheal paragangliomas and describe the clinical presentation, radiologic findings, operative management, and histologic findings of a pediatric patient who presented with stridor refractory to traditional asthma therapy.MethodsChart review of an 8-year-old male who presented to a tertiary care pediatric hospital and literature review of tracheal paragangliomas.ResultsWe present the case of an 8-year-old male who presented with new-onset of wheezing and dyspnea on exertion. He was given a new diagnosis of asthma and treated with bronchodilators that failed to improve his symptoms, which progressed over 3 months until he presented urgently with biphasic stridor. Bedside flexible laryngoscopy failed to reveal an etiology. Computed tomography (CT) imaging demonstrated 17 × 12 × 16 mm exophytic mass arising from the posterior membranous trachea with extension of the mass to the border of the thyroid gland and separate from the esophagus. Magnetic resonance imaging (MRI) angiography confirmed vascular supply from the right thyrocervical trunk and inferior thyroid artery. Rigid microlaryngoscopy revealed a friable vascular polypoid mass 2 cm distal to the vocal folds with 75% obstruction of the airway from which a small biopsy was taken. Pathology confirmed paraganglioma with neuroendocrine cells arranged in "zellballen" architecture and strong immunopositivity for chromogranin and synaptophysin in the neuroendocrine cells and S100 immunopositivity in the sustentacular cells. The patient underwent complete open resection of the tumor including three tracheal rings with primary anastomosis. Final pathology confirmed paraganglioma and negative margins. Genetic screening revealed a succinate dehydrogenase complex subunit C (SDHC) germline mutation, confirming hereditary paraganglioma/pheochromocytoma syndrome. He remains well at 3 month follow up without dyspnea or stridor.ConclusionTracheal paragangliomas are exceptionally rare, with 12 reported cases. This is the only pediatric case reported. In pediatric patients with persistent airway complaints, subglottic and tracheal masses and obstruction should be considered. Due to the vascularity and endotracheal component of tracheal paragangliomas, a detailed surgical plan should consider embolization, endotracheal laser photocoagulation and electrocautery, and open surgical resection. Additionally, pediatric patients benefit from a multidisciplinary approach including radiology, endocrinology, and genetic counseling.



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Geographic health disparities in the Los Angeles pediatric esophageal foreign body population

Publication date: March 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 106
Author(s): Kevin Hur, Varun Angajala, Dennis Maceri, Christian Hochstim
ObjectiveTo assess geographical sociodemographic differences in the pediatric esophageal foreign body population of Los Angeles.MethodsWe retrospectively reviewed the medical records of 128 consecutive pediatric patients at Children's Hospital Los Angeles (CHLA) from 2014 to 2017 with a diagnosis of a retained foreign body in the esophagus removed by rigid or flexible esophagoscopy. Sociodemographic information including zip code of residence was extracted and analyzed with Chi-square, Fisher's exact test, and multivariable logistic regression.ResultsThe average age of patients with a retained esophageal foreign body in this study was 2.5 years old, 52.3% were male, 91.4% had no past medical history, 53.1% were Hispanic, 82.0% had public health insurance, and 63.3% were transfers from an outside hospital. The most common foreign body removed was a coin. There were no significant differences in gender, race, type of health insurance, or income between patients that lived within 10 miles of CHLA versus farther than 10 miles. On multivariable analysis, zip codes with a high volume of esophageal foreign bodies were more likely to be lower income neighborhoods. Gender, race, type of health insurance, and distance from CHLA were not risk factors for zip codes with a high volume of esophageal foreign bodies.ConclusionGeographic areas in the greater Los Angeles community with a high volume of retained esophageal foreign bodies requiring endoscopic removal at our institution are associated with lower income neighborhoods. Further studies should be performed to better understand health disparities within the U.S. pediatric esophageal foreign body population.



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Meta-analysis of the comorbidity rate of allergic rhinitis and asthma in Chinese children

Publication date: Available online 5 February 2018
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Wei Kou, Xuelei Li, Hongbing Yao, Ping Wei
ObjectivesAllergic rhinitis (AR) and asthma often occur concomitantly and are the two most common inflammatory conditions of the airways in children. Large-scale studies investigating the comorbidity of asthma and AR in children are rare. So, we performed a meta-analysis to describe the comorbidity rate of asthma and AR in Chinese children.MethodsWe retrieved related studies from Pubmed, Science, Springer, Elsevier, Embase, BMJ, and four Chinese biomedical databases, including Wanfang Data, VIP, CBM, and CNKI. From these individual studies, the comorbidity rate of asthma and AR in Chinese children was extracted and pooled to generate summary effect estimates in R version 3.2.3.ResultsThe meta-analysis included 25 cross-sectional studies. The results indicated that in China, the incidence of asthma in children with AR is 35.01% (95% CI: 32.32%–37.70%) and the incidence of AR in children with asthma is 54.93% (95% CI: 53.05%–56.80%).ConclusionsThe comorbidity of AR and asthma is high in Chinese children. Statistically, the prevalence of AR was higher in children with asthma, as opposed to the prevalence of asthma in children with AR. The comorbidity rate of AR and asthma signifies the importance of improving the recognition and treatment under both conditions by respiratory physicians and otolaryngologists.



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Microbiology and antibiotic therapy of subperiosteal orbital abscess in children with acute ethmoiditis

Publication date: March 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 106
Author(s): A. Coudert, S. Ayari-Khalfallah, P. Suy, E. Truy
ObjectiveThe objective of this study was to investigate the microbiological cultures and the management of acute ethmoiditis complicated by subperiosteal orbital abscess (SPOA) in a pediatric population.MethodsThe medical records of children under 18 years old was performed in a tertiary referral pediatric center from January 2009 to April 2017. Clinical examination, computed tomography scans, medical and surgical treatments were reviewed and compared to other studies in literature.ResultsOne hundred and twenty-nine children were hospitalized for acute ethmoiditis. Among them, forty eight were complicated by SPOA. The mean age of these children were 7 years (range 10 months–16 years). Thirtyfour underwent surgical drainage; for the others the medical treatment was sufficient. Microbiological samples were obtained during the surgical intervention and were contributive in 91% of cases. Streptococcus spp was the most frequently encountered bacteria (60% of cases). We also found anaerobic bacteria (12%), and Staphylococcus aureus (12%). 94% of children received two intravenous antibiotics (a third-generation cephalosporin and metronidazole) for a mean duration of four days. Then the oral treatment was based on amoxicillin-clavulanate during about 8.5 days. All children were cured without sequelae.ConclusionsFor five years Streptococcus milleri, Staphylococcus spp and anaerobic bacteria are on the rise in acute ethmoiditis complicated by SPOA. That is why antibiotics must be adapted to these bacteria even in children under ten years old.



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Human beta defensin-1 is involved in the susceptibility to adenotonsillar hipertrophy

Publication date: Available online 5 February 2018
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Luisa Zupin, Fulvio Celsi, Martina Bresciani, Eva Orzan, Domenico Leonardo Grasso, Sergio Crovella
IntroductionInnate immunity molecules are known to play a pivotal role in the homeostasis of the oral mucosa, permitting the presence of commensal microflora and, at the same time, providing a first line of defense against pathogens attempting to invade the oral cavity.Tonsils represent the local immune tissue in oral cavity, being able to provide a non-specific response to pathogens; however, in the presence of microbes or foreign materials present in the mouth tonsils could became infected and develop chronic inflammation, thus leading to hypertrophy.The etiology of the disease is multifactorial depending upon environmental and host factors, the latter including molecules of mucosal innate immunity.MethodsNinety-five children with adeno-tonsillar hypertrophy subjected to adeno-tonsillectomy were recruited at the pediatric otorhinolaryngology service of the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste (Italy).The specimen discard from the surgery were used for genomic DNA extraction and genotyping, for mRNA extraction and gene expression analysis, finally the samples were cut and used to prepare slides to perform immunohistochemistry.ResultsFunctional polymorphisms within DEFB1 gene, encoding the human beta defensin-1 (hBD-1), were analyzed finding association between DEFB1 rare haplotypes and susceptibility to adenotonsillar hypertrophy. DEFB1 mRNA expression was detected in the tonsils and the hBD-1 protein was localized at the epithelia of tonsils mainly in the proximity of the basal lamina.ConclusionOur findings lead us to hypothesize an involvement of hBD-1 mediated innate immunity in the modulation of the susceptibility towards adenotonsillar hypertrophy development.



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Analysis of risk factors associated with unilateral hearing loss in children who initially passed newborn hearing screening

Publication date: March 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 106
Author(s): Eric N. Appelbaum, Jessica B. Howell, Derek Chapman, Arti Pandya, Kelley M. Dodson
ObjectiveTo analyze 2007 Joint Committee on Infant Hearing (JCIH) risk factors in children with confirmed unilateral hearing loss (UHL) who initially passed newborn hearing screening.MethodsRetrospective record review of 16,108 infants who passed newborn hearing screening but had one or more JCIH risk factors prompting subsequent follow-up through the universal newborn hearing screening (UNHS) program in Virginia from 2010 to 2012. The study was reviewed and qualified as exempt by the Virginia Commonwealth University Institutional Review Board (IRB) and the Virginia Department of Health.ResultsOver the 2-year study period, 14896 (4.9% of total births) children passed UNHS but had the presence of one or more JCIH risk factor. Ultimately, we identified 121 babies from this group with confirmed hearing loss (0.7%), with 48 babies (0.2%) showing UHL. The most common risk factors associated with the development of confirmed UHL after passing the initial screen were neonatal indicators, craniofacial anomalies, family history, and stigmata of syndrome associated with hearing loss.ConclusionNeonatal indicators and craniofacial anomalies were the categories most often found in children with confirmed unilateral hearing loss who initially passed their newborn hearing screen. While neonatal indicators were also the most common associated risk factor in all hearing loss, craniofacial abnormalities are relatively more common in children with UHL who initially passed newborn hearing screening. Further studies assessing the etiology underlying the hearing loss and risk factor associations are warranted.



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Tympanostomy tubes for serous otitis media and risk of recurrences

Publication date: March 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 106
Author(s): Nathalie Klopp-Dutote, Catherine Kolski, Vladimir Strunski, Cyril Page
ObjectivesTo determine the value of tympanostomy tubes (TTs) in the management of serous otitis media (SOM) and the risk factors for SOM recurrence.MethodThis single-centre cohort study was performed in the University hospital of Amiens, France; and concerned 215 under-12 children having undergone at least one bilateral TT (Shepard grommet-type) placements for SOM.ResultsThe mean TT retention time was 10 months. SOM recurred in 79 children (62.79%) and thus required a second TT placement (bilaterally in 90% of these cases). Overall, 29.3% of the patients underwent a total of two TT placements, 5.58% underwent three placements and 0.93% underwent four placements. After their first-ever TT placement, 17 children had complications: 10 cases of otorrhoea (4.6%), 4 cases of retraction pocket (1.9%) and 3 perforations of the tympanic membrane (1.4%). At last follow-up, the most common complications were tympanosclerosis (6.9%) and perforation of the tympanic membrane (6.5%). In a multivariate analysis, the only significant risk factors for SOM recurrence were age below 48 months at the time of TT placement, and a TT retention time below 9 months. In contrast, a history of allergy, gastro-oesophageal reflux, prematurity or passive smoking were not significantly associated with recurrence.ConclusionAge at the time of TT placement and the TT retention time were significantly associated with SOM recurrence. The TT retention time and the number of TT placements were not associated with the risk of long-term complications.



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Cochlear implantation in pediatric patients with Cockayne Syndrome

Publication date: March 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 106
Author(s): Renae D. Van Wyhe, Claudia V. Emery, Robert A. Williamson
Cockayne Syndrome (CS) is a rare, autosomal recessive disorder characterized by a spectrum of phenotypic abnormalities, including progressive sensorineural hearing loss (SNHL) that involves both peripheral and central components. To date, a single series of CS patients undergoing cochlear implant (CI) placement has been reported; this study reports on additional previously unreported pediatric CI recipients. Subjective benefits were noted early after activation in both patients, and speech perception scores improved over time as well, varying from 42 to 70% (versus 0–12% previously). Thus, we report that cochlear implantation in pediatric patients with CS can be effective in the management of progressive SNHL.



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Acute external otitis as debut of acute myeloid leukemia - A case and review of the literature

Publication date: March 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 106
Author(s): Joachim Slengerik-Hansen, Therese Ovesen
Acute leukemia is a well known childhood cancer. The relation between leukemia and otological symptoms has long been established but is highly rare as a debut symptom of leukemia. External otitis is a common condition affecting many children, and most cases are successively treated with topical medicine. Here we present a child with acute external otitis later shown to be the debut symptom of acute myeloid leukemia, to our knowledge the first specific case described. We have reviewed the literature to find red flags for suspicion of severe disease in case of acute external otitis.



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Vastus lateralis motor unit firing rate is higher in females with patellofemoral pain

Publication date: Available online 10 February 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Alessio Gallina, Michael A. Hunt, Paul Hodges, S. Jayne Garland
ObjectiveTo compare neural drive, determined from motor unit firing rate, to the vastus medialis and lateralis in females with and without patellofemoral pain.DesignCross-sectional study.SettingUniversity research laboratory.ParticipantsFemales (N=56) 19-35 years old, 36 with patellofemoral pain and 20 controls. Interventions: Not applicable.Main Outcome Measure(s)Participants sustained an isometric knee extension contraction at 10% of their maximal voluntary effort for 70s. Motor units (N=414) were identified using high-density surface electromyography. Average firing rate was calculated between 5 and 35s after recruitment for each motor unit. Initial firing rate was the inverse of the first three motor unit inter-spike intervals.ResultsIn control participants, vastus medialis motor units discharged at higher rates than vastus lateralis (p=0.001). This was not observed in females with patellofemoral pain (p=0.78) due to a higher discharge rate of vastus lateralis compared to control participants (p=0.002). No between-group differences were observed for vastus medialis (p=0.93). Similar results were obtained for the initial motor unit firing rate.ConclusionsThese findings suggest that females with patellofemoral pain have a higher neural drive to vastus lateralis but not vastus medialis, which may be a contributor of the altered patellar kinematics observed in some studies. The different neural drive may be an adaptation to patellofemoral pain, possibly to compensate for decreased quadriceps force production, or a precursor of patellofemoral pain.



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The clinical assessment of spasticity in people with spinal cord damage: recommendations from the Ability Network, an international initiative

Publication date: Available online 10 February 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Anand V. Nene, Alexandre Rainha Campos, Klemen Grabljevec, Arminda Lopes, Bengt Skoog, Anthony S. Burns
A thorough assessment of the extent and severity of spasticity, and its impact on functioning, is central to the effective management of spasticity in persons with spinal cord damage (SCD). These individuals, however, do not always receive adequate assessment of their spasticity. Inadequate assessment compromises management when the impact of spasticity and/or need for intervention are not fully recognized. Assessment is also central to determining treatment efficacy. A barrier to spasticity assessment has been the lack of consensus on clinical and functional measures suitable for routine clinical practice. To extend upon existing work, a working group of the Ability Network identified and consolidated information on possible measures, then synthesized and formulated findings into practical recommendations for assessing spasticity and its impact on function in persons with SCD. Sixteen clinical and functional measures that have been used for this purpose were identified using a targeted literature review. These were mapped to the relevant domains of the International Classification of Functioning, Disability and Health (ICF) to assess the breadth of their coverage; coverage of many domains was found to be lacking, suggesting a focus for future work. The advantages, disadvantages and usefulness of the measures were assessed using a range of criteria, with a focus on usefulness and feasibility in routine clinical practice. Based on this evaluation, a selection of measures suitable for initial and follow-up assessments are recommended. The recommendations are intended to have broad applicability to a variety of healthcare settings where people with SCD are managed.



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Screening for Abdominal Aortic Aneurysm During Transthoracic Echocardiography: A Systematic Review and Meta-analysis

Publication date: Available online 9 February 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Christos Argyriou, George S. Georgiadis, Nikolaos Kontopodis, Arun D. Pherwani, Joost A. Van Herwaarden, Constantijn E.V.B. Hazenberg, George A. Antoniou
BackgroundScreening for abdominal aortic aneurysm (AAA) during transthoracic echocardiography (TTE) may be an effective targeted screening strategy.ObjectiveThe aim was to assess the feasibility of AAA screening during TTE and to estimate the prevalence of AAA in patients undergoing TTE.MethodsElectronic bibliographic sources were interrogated using a combination of free text and controlled vocabulary searches to identify studies reporting on AAA screening during TTE. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards. Fixed effect or random effects models were used to calculate pooled prevalence estimates.ResultsTwenty observational cohort studies were identified reporting a total of 43,341 participants (23,291 men and 20,050 women). Hypertension was reported in 41% (95% CI 38–43), hypercholesterolemia in 31% (95% CI 29–32), diabetes mellitus in 20% (95% CI 19–22), and tobacco use in 37% (95% CI 35–38). The aorta was visualised in 86% (95% CI 84–88) of the screened population. The pooled prevalence of AAA in the entire screened population was 0.033 (95% CI 0.024–0.044). The pooled prevalence of AAA in men was 0.046 (95% CI 0.032–0.065) and in women it was 0.014 (95% CI 0.008–0.022). The mean age of participants in whom an AAA was detected ranged across the studies from 66 to 85 years. The mean diameter of the aneurysm identified ranged across the studies from 35 mm to 45 mm. Clinical outcomes in participants with a detected AAA were poorly reported.ConclusionsScreening for AAA during TTE may identify a population group with a high risk of AAA in whom targeted screening may be beneficial. Further research is required to investigate the cost-effectiveness and clinical benefits of AAA screening in this setting.



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The Marburg-Münster Affective Disorders Cohort Study (MACS): A quality assurance protocol for MR neuroimaging data

Publication date: 15 May 2018
Source:NeuroImage, Volume 172
Author(s): Christoph Vogelbacher, Thomas W.D. Möbius, Jens Sommer, Verena Schuster, Udo Dannlowski, Tilo Kircher, Astrid Dempfle, Andreas Jansen, Miriam H.A. Bopp
Large, longitudinal, multi-center MR neuroimaging studies require comprehensive quality assurance (QA) protocols for assessing the general quality of the compiled data, indicating potential malfunctions in the scanning equipment, and evaluating inter-site differences that need to be accounted for in subsequent analyses.We describe the implementation of a QA protocol for functional magnet resonance imaging (fMRI) data based on the regular measurement of an MRI phantom and an extensive variety of currently published QA statistics. The protocol is implemented in the MACS (Marburg-Münster Affective Disorders Cohort Study, http://for2107.de/), a two-center research consortium studying the neurobiological foundations of affective disorders. Between February 2015 and October 2016, 1214 phantom measurements have been acquired using a standard fMRI protocol. Using 444 healthy control subjects which have been measured between 2014 and 2016 in the cohort, we investigate the extent of between-site differences in contrast to the dependence on subject-specific covariates (age and sex) for structural MRI, fMRI, and diffusion tensor imaging (DTI) data.We show that most of the presented QA statistics differ severely not only between the two scanners used for the cohort but also between experimental settings (e.g. hardware and software changes), demonstrate that some of these statistics depend on external variables (e.g. time of day, temperature), highlight their strong dependence on proper handling of the MRI phantom, and show how the use of a phantom holder may balance this dependence. Site effects, however, do not only exist for the phantom data, but also for human MRI data. Using T1-weighted structural images, we show that total intracranial (TIV), grey matter (GMV), and white matter (WMV) volumes significantly differ between the MR scanners, showing large effect sizes. Voxel-based morphometry (VBM) analyses show that these structural differences observed between scanners are most pronounced in the bilateral basal ganglia, thalamus, and posterior regions. Using DTI data, we also show that fractional anisotropy (FA) differs between sites in almost all regions assessed. When pooling data from multiple centers, our data show that it is a necessity to account not only for inter-site differences but also for hardware and software changes of the scanning equipment. Also, the strong dependence of the QA statistics on the reliable placement of the MRI phantom shows that the use of a phantom holder is recommended to reduce the variance of the QA statistics and thus to increase the probability of detecting potential scanner malfunctions.



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