Consolidation Chemotherapy After Concurrent Chemoradiotherapy in Patients With Stage III Non-Small-Cell Lung Cancer CORRESPONDENCE

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Assessment of Primary Site Response in Children With High-Risk Neuroblastoma: An International Multicenter Study Pediatric Oncology

Purpose

The International Neuroblastoma Response Criteria (INRC) require serial measurements of primary tumors in three dimensions, whereas the Response Evaluation Criteria in Solid Tumors (RECIST) require measurement in one dimension. This study was conducted to identify the preferred method of primary tumor response assessment for use in revised INRC.

Patients and Methods

Patients younger than 20 years with high-risk neuroblastoma were eligible if they were diagnosed between 2000 and 2012 and if three primary tumor measurements (antero-posterior, width, cranio-caudal) were recorded at least twice before resection. Responses were defined as ≥ 30% reduction in longest dimension as per RECIST, ≥ 50% reduction in volume as per INRC, or ≥ 65% reduction in volume.

Results

Three-year event-free survival for all patients (N = 229) was 44% and overall survival was 58%. The sensitivity of both volume response measures (ability to detect responses in patients who survived) exceeded the sensitivity of the single dimension measure, but the specificity of all response measures (ability to identify lack of response in patients who later died) was low. In multivariable analyses, none of the response measures studied was predictive of outcome, and none was predictive of the extent of resection.

Conclusion

None of the methods of primary tumor response assessment was predictive of outcome. Measurement of three dimensions followed by calculation of resultant volume is more complex than measurement of a single dimension. Primary tumor response in children with high-risk neuroblastoma should therefore be evaluated in accordance with RECIST criteria, using the single longest dimension.

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Are lung cancer survivors getting too many costly scans for no reason? Study suggests so.

Once you've made it through lung cancer treatment, you want to make sure you catch it early if it comes back again. But a new study suggests that one approach to watching for a cancer's return is being inappropriately used at many hospitals. And it…

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Intramuscular fat and physical performance at the Framingham Heart Study

Abstract

Intramuscular fat may mediate associations between obesity and physical disability. We examined the associations between muscle attenuation, a proxy for intramuscular fat, and physical function. Paraspinous muscle computed tomography attenuation was obtained on a Framingham Heart Study subgroup (n = 1152, 56 % women, mean age 66 years). Regressions modeled cross-sectional associations between muscle attenuation and mobility disability, grip strength, and walking speed with standard covariates; models additionally adjusted for body mass index (BMI) and visceral adipose tissue (VAT). Separate models investigated associations between VAT and subcutaneous adipose tissue (SAT) and physical function. Per 1 standard deviation decrement in muscle attenuation (i.e., more muscle fat), we observed 1.29 (95 % CI = 1.11, 1.50; p = 0.0009) increased odds of walking speed ≤1 m/s in women and men. This persisted after separate BMI and VAT adjustments (p < 0.02). In men, there was a 1.29 kg (95 % CI = 0.57, 2.01; p = 0.0005) decrement in grip strength, which persisted after BMI and VAT adjustments (p ≤ 0.0004). For VAT and SAT, similar associations were not observed. Intramuscular fat is associated with increased odds of walking speed ≤1 m/s in both sexes and lower grip strength in men. There were no similar associations for VAT and SAT, highlighting the specificity of intramuscular fat in association with physical function.

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Randomized Trial Comparing Telephone Versus In-Person Weight Loss Counseling on Body Composition and Circulating Biomarkers in Women Treated for Breast Cancer: The Lifestyle, Exercise, and Nutrition (LEAN) Study Cancer Prevention and Control

Purpose

Obesity is associated with a higher risk of breast cancer mortality. The gold standard approach to weight loss is in-person counseling, but telephone counseling may be more feasible. We examined the effect of in-person versus telephone weight loss counseling versus usual care on 6-month changes in body composition, physical activity, diet, and serum biomarkers.

Methods

One hundred breast cancer survivors with a body mass index ≥ 25 kg/m2 were randomly assigned to in-person counseling (n = 33), telephone counseling (n = 34), or usual care (UC) (n = 33). In-person and telephone counseling included 11 30-minute counseling sessions over 6 months. These focused on reducing caloric intake, increasing physical activity, and behavioral therapy. Body composition, physical activity, diet, and serum biomarkers were measured at baseline and 6 months.

Results

The mean age of participants was 59 ± 7.5 years old, with a mean BMI of 33.1 ± 6.6 kg/m2, and the mean time from diagnosis was 2.9 ± 2.1 years. Fifty-one percent of the participants had stage I breast cancer. Average 6-month weight loss was 6.4%, 5.4%, and 2.0% for in-person, telephone, and UC groups, respectively (P = .004, P = .009, and P = .46 comparing in-person with UC, telephone with UC, and in-person with telephone, respectively). A significant 30% decrease in C-reactive protein levels was observed among women randomly assigned to the combined weight loss intervention groups compared with a 1% decrease among women randomly assigned to UC (P = .05).

Conclusion

Both in-person and telephone counseling were effective weight loss strategies, with favorable effects on C-reactive protein levels. Our findings may help guide the incorporation of weight loss counseling into breast cancer treatment and care.

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MET Exon 14 Mutations in Non-Small-Cell Lung Cancer Are Associated With Advanced Age and Stage-Dependent MET Genomic Amplification and c-Met Overexpression Thoracic Oncology

Purpose

Non–small-cell lung cancers (NSCLCs) harboring mutations in MET exon 14 and its flanking introns may respond to c-Met inhibitors. We sought to describe the clinical, pathologic, and genomic characteristics of patients with cancer with MET exon 14 mutations.

Patients and Methods

We interrogated next-generation sequencing results from 6,376 cancers to identify those harboring MET exon 14 mutations. Clinical characteristics of MET exon 14 mutated NSCLCs were compared with those of NSCLCs with activating mutations in KRAS and EGFR. Co-occurring genomic mutations and copy number alterations were identified. c-Met immunohistochemistry and real-time polymerase chain reaction to detect exon 14 skipping were performed where sufficient tissue was available.

Results

MET exon 14 mutations were identified in 28 of 933 nonsquamous NSCLCs (3.0%) and were not seen in other cancer types in this study. Patients with MET exon 14–mutated NSCLC were significantly older (median age, 72.5 years) than patients with EGFR-mutant (median age, 61 years; P < .001) or KRAS-mutant NSCLC (median age, 65 years; P < .001). Among patients with MET exon 14 mutations, 68% were women, and 36% were never-smokers. Stage IV MET exon 14–mutated NSCLCs were significantly more likely to have concurrent MET genomic amplification (mean ratio of MET to chromosome 7, 4.3) and strong c-Met immunohistochemical expression (mean H score, 253) than stage IA to IIIB MET exon 14–mutated NSCLCs (mean ratio of MET to chromosome 7, 1.4; P = .007; mean H score, 155; P = .002) and stage IV MET exon 14–wild-type NSCLCs (mean ratio of MET to chromosome 7, 1.2; P < .001; mean H score, 142; P < .001). A patient whose lung cancer harbored a MET exon 14 mutation with concurrent genomic amplification of the mutated MET allele experienced a major partial response to the c-Met inhibitor crizotinib.

Conclusion

MET exon 14 mutations represent a clinically unique molecular subtype of NSCLC. Prospective clinical trials with c-Met inhibitors will be necessary to validate MET exon 14 mutations as an important therapeutic target in NSCLC.

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Volasertib Versus Chemotherapy in Platinum-Resistant or -Refractory Ovarian Cancer: A Randomized Phase II Groupe des Investigateurs Nationaux pour l’Etude des Cancers de l’Ovaire Study Gynecologic Cancer

Purpose

Volasertib is a potent and selective cell-cycle kinase inhibitor that induces mitotic arrest and apoptosis by targeting Polo-like kinase. This phase II trial evaluated volasertib or single-agent chemotherapy in patients with platinum-resistant or -refractory ovarian cancer who experienced failure after treatment with two or three therapy lines.

Patients and Methods

Patients were randomly assigned to receive either volasertib 300 mg by intravenous infusion every 3 weeks or an investigator's choice of single-agent, nonplatinum, cytotoxic chemotherapy. The primary end point was 24-week disease control rate. Secondary end points included best overall response, progression-free survival (PFS), safety, quality of life, and exploratory biomarker analyses.

Results

Of the 109 patients receiving treatment, 54 received volasertib and 55 received chemotherapy; demographics were well balanced. The 24-week disease control rates for volasertib and chemotherapy were 30.6% (95% CI, 18.0% to 43.2%) and 43.1% (95% CI, 29.6% to 56.7%), respectively, with partial responses in seven (13.0%) and eight (14.5%) patients, respectively. Median PFS was 13.1 weeks and 20.6 weeks for volasertib and chemotherapy (hazard ratio, 1.01; 95% CI, 0.66 to 1.53). Six patients (11%) receiving volasertib achieved PFS fore more than 1 year, whereas no patient receiving chemotherapy achieved PFS greater than 1 year. No relationship between the expression of the biomarkers tested and their response was determined. Patients treated with volasertib experienced more grade 3 and 4 drug-related hematologic adverse events (AEs) and fewer nonhematologic AEs than did patients receiving chemotherapy. Discontinuation resulting from AEs occurred in seven (13.0%) and 15 (27.3%) patients in the volasertib and chemotherapy arms, respectively. Both arms showed similar effects on quality of life.

Conclusion

Single-agent volasertib showed antitumor activity in patients with ovarian cancer. AEs in patients receiving volasertib were mainly hematologic and manageable.

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Conditional Survival of Patients With Metastatic Testicular Germ Cell Tumors Treated With First-Line Curative Therapy Urologic Oncology

Purpose

The International Germ Cell Cancer Collaborative Group (IGCCCG) criteria prognosticate survival outcomes in metastatic testicular germ cell tumor (MT-GCT), but how the initial risk changes over time for those who survived since curative treatment is unknown.

Patients and Methods

We assessed patients eligible for first-line therapy for MT-GCT at five tertiary cancer centers from 1990 to 2012 for 2-year conditional overall survival (COS) and conditional disease-free survival (CDFS), defined as the probability of surviving, or surviving and being disease free, respectively, for an additional 2 years at a given time point since the initial diagnosis.

Results

For all patients (N = 942), 2-year COS increased from 92% (95% CI, 91% to 94%) at 0 months to 98% (95% CI, 97% to 99%), and 2-year CDFS increased from 83% (95% CI, 81% to 86%) at baseline to 98% (95% CI, 97% to 99%) at 24 months after diagnosis. Two-year COS improved by 2% (97% at 0 months, 99% at 24 months) in the IGCCCG favorable-risk group, by 5% (94% at 0 months, 99% at 24 months) in the intermediate-risk group, and by 22% (71% at 0 months to 93% at 24 months) in the poor-risk group. Two-year CDFS improved significantly at 12 months for each risk group (favorable, 91% baseline v 95% at 12 months; intermediate, 84% v 95%; poor, 55% v 85%). Baseline IGCCCG risk stratification was not associated with long-term COS or CDFS for patients who survived to greater than 2 years post therapy. No significant differences in COS and CDFS were noted between seminoma and nonseminoma; patients ≥ 40 years old had inferior 2-year COS from 0 to 12 months, but no differences were noted at 18 months.

Conclusion

Our data suggest that the concept of conditional survival applies to patients with MT-GCT treated with curative therapy. Patients with MT-GCT who survived and remained disease free more than 2 years after the diagnosis had an excellent chance of staying alive and disease free in additional subsequent years, regardless of the initial IGCCCG risk stratification.

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Histone variants and melanoma: facts and hypotheses

Abstract

Melanoma is the most aggressive form of skin cancer with rising incidence and morbidity. Despite advances in treatment, the 10-year survival for patients with metastatic disease is less than 10%. During the past few years, ongoing research on different epigenomic aberrations in melanoma has catalyzed better understanding of its pathogenesis and identification of new therapeutics. In our review we will focus on the role of histone variants, key epigenetic players in melanoma initiation and progression. Specifically, incorporation of histone variants enables additional layers of chromatin structure and here we will describe how alterations in this epigenetic behavior impact melanoma.

This article is protected by copyright. All rights reserved.

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Treating thyroid lymphoma – The Straits Times

Treating thyroid lymphoma The Straits Times It is the fifth-most-common cancer in men and sixth-most-common cancer in women, according to the Singapore Cancer Registry 2010-14. However, thyroid lymphomas are not common and account for only 1 to 2 per cent of all lymphomas. While the exact …

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Red meat, poultry, and fish intake and breast cancer risk among Hispanic and Non-Hispanic white women: The Breast Cancer Health Disparities Study

Abstract

Purpose

There is suggestive but limited evidence for a relationship between meat intake and breast cancer (BC) risk. Few studies included Hispanic women. We investigated the association between meats and fish intake and BC risk among Hispanic and NHW women.

Methods

The study included NHW (1,982 cases and 2,218 controls) and the US Hispanics (1,777 cases and 2,218 controls) from two population-based case–control studies. Analyses considered menopausal status and percent Native American ancestry. We estimated pooled ORs combining harmonized data from both studies, and study- and race-/ethnicity-specific ORs that were combined using fixed or random effects models, depending on heterogeneity levels.

Results

When comparing highest versus lowest tertile of intake, among NHW we observed an association between tuna intake and BC risk (pooled OR 1.25; 95 % CI 1.05–1.50; trend p = 0.006). Among Hispanics, we observed an association between BC risk and processed meat intake (pooled OR 1.42; 95 % CI 1.18–1.71; trend p < 0.001), and between white meat (OR 0.80; 95 % CI 0.67–0.95; trend p = 0.01) and BC risk, driven by poultry. All these findings were supported by meta-analysis using fixed or random effect models and were restricted to estrogen receptor-positive tumors. Processed meats and poultry were not associated with BC risk among NHW women; red meat and fish were not associated with BC risk in either race/ethnic groups.

Conclusions

Our results suggest the presence of ethnic differences in associations between meat and BC risk that may contribute to BC disparities.

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Markers, Models, and Measurement Error: Exploring the Links Between Attention Deficits and Language Impairments

Purpose

The empirical record regarding the expected co-occurrence of attention-deficit/hyperactivity disorder (ADHD) and specific language impairment is confusing and contradictory. A research plan is presented that has the potential to untangle links between these 2 common neurodevelopmental disorders.

Method

Data from completed and ongoing research projects examining the relative value of different clinical markers for separating cases of specific language impairment from ADHD are presented.

Results

The best option for measuring core language impairments in a manner that does not potentially penalize individuals with ADHD is to focus assessment on key grammatical and verbal memory skills. Likewise, assessment of ADHD symptoms through standardized informant rating scales is optimized when they are adjusted for overlapping language and academic symptoms.

Conclusion

As a collection, these clinical metrics set the stage for further examination of potential linkages between attention deficits and language impairments.

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Markers, Models, and Measurement Error: Exploring the Links Between Attention Deficits and Language Impairments

Purpose

The empirical record regarding the expected co-occurrence of attention-deficit/hyperactivity disorder (ADHD) and specific language impairment is confusing and contradictory. A research plan is presented that has the potential to untangle links between these 2 common neurodevelopmental disorders.

Method

Data from completed and ongoing research projects examining the relative value of different clinical markers for separating cases of specific language impairment from ADHD are presented.

Results

The best option for measuring core language impairments in a manner that does not potentially penalize individuals with ADHD is to focus assessment on key grammatical and verbal memory skills. Likewise, assessment of ADHD symptoms through standardized informant rating scales is optimized when they are adjusted for overlapping language and academic symptoms.

Conclusion

As a collection, these clinical metrics set the stage for further examination of potential linkages between attention deficits and language impairments.

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Prosody and Semantics Are Separate but Not Separable Channels in the Perception of Emotional Speech: Test for Rating of Emotions in Speech

Purpose

Our aim is to explore the complex interplay of prosody (tone of speech) and semantics (verbal content) in the perception of discrete emotions in speech.

Method

We implement a novel tool, the Test for Rating of Emotions in Speech. Eighty native English speakers were presented with spoken sentences made of different combinations of 5 discrete emotions (anger, fear, happiness, sadness, and neutral) presented in prosody and semantics. Listeners were asked to rate the sentence as a whole, integrating both speech channels, or to focus on one channel only (prosody or semantics).

Results

We observed supremacy of congruency, failure of selective attention, and prosodic dominance. Supremacy of congruency means that a sentence that presents the same emotion in both speech channels was rated highest; failure of selective attention means that listeners were unable to selectively attend to one channel when instructed; and prosodic dominance means that prosodic information plays a larger role than semantics in processing emotional speech.

Conclusions

Emotional prosody and semantics are separate but not separable channels, and it is difficult to perceive one without the influence of the other. Our findings indicate that the Test for Rating of Emotions in Speech can reveal specific aspects in the processing of emotional speech and may in the future prove useful for understanding emotion-processing deficits in individuals with pathologies.

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Prosody and Semantics Are Separate but Not Separable Channels in the Perception of Emotional Speech: Test for Rating of Emotions in Speech

Purpose

Our aim is to explore the complex interplay of prosody (tone of speech) and semantics (verbal content) in the perception of discrete emotions in speech.

Method

We implement a novel tool, the Test for Rating of Emotions in Speech. Eighty native English speakers were presented with spoken sentences made of different combinations of 5 discrete emotions (anger, fear, happiness, sadness, and neutral) presented in prosody and semantics. Listeners were asked to rate the sentence as a whole, integrating both speech channels, or to focus on one channel only (prosody or semantics).

Results

We observed supremacy of congruency, failure of selective attention, and prosodic dominance. Supremacy of congruency means that a sentence that presents the same emotion in both speech channels was rated highest; failure of selective attention means that listeners were unable to selectively attend to one channel when instructed; and prosodic dominance means that prosodic information plays a larger role than semantics in processing emotional speech.

Conclusions

Emotional prosody and semantics are separate but not separable channels, and it is difficult to perceive one without the influence of the other. Our findings indicate that the Test for Rating of Emotions in Speech can reveal specific aspects in the processing of emotional speech and may in the future prove useful for understanding emotion-processing deficits in individuals with pathologies.

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Prosody and Semantics Are Separate but Not Separable Channels in the Perception of Emotional Speech: Test for Rating of Emotions in Speech

Purpose

Our aim is to explore the complex interplay of prosody (tone of speech) and semantics (verbal content) in the perception of discrete emotions in speech.

Method

We implement a novel tool, the Test for Rating of Emotions in Speech. Eighty native English speakers were presented with spoken sentences made of different combinations of 5 discrete emotions (anger, fear, happiness, sadness, and neutral) presented in prosody and semantics. Listeners were asked to rate the sentence as a whole, integrating both speech channels, or to focus on one channel only (prosody or semantics).

Results

We observed supremacy of congruency, failure of selective attention, and prosodic dominance. Supremacy of congruency means that a sentence that presents the same emotion in both speech channels was rated highest; failure of selective attention means that listeners were unable to selectively attend to one channel when instructed; and prosodic dominance means that prosodic information plays a larger role than semantics in processing emotional speech.

Conclusions

Emotional prosody and semantics are separate but not separable channels, and it is difficult to perceive one without the influence of the other. Our findings indicate that the Test for Rating of Emotions in Speech can reveal specific aspects in the processing of emotional speech and may in the future prove useful for understanding emotion-processing deficits in individuals with pathologies.

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Markers, Models, and Measurement Error: Exploring the Links Between Attention Deficits and Language Impairments

Purpose

The empirical record regarding the expected co-occurrence of attention-deficit/hyperactivity disorder (ADHD) and specific language impairment is confusing and contradictory. A research plan is presented that has the potential to untangle links between these 2 common neurodevelopmental disorders.

Method

Data from completed and ongoing research projects examining the relative value of different clinical markers for separating cases of specific language impairment from ADHD are presented.

Results

The best option for measuring core language impairments in a manner that does not potentially penalize individuals with ADHD is to focus assessment on key grammatical and verbal memory skills. Likewise, assessment of ADHD symptoms through standardized informant rating scales is optimized when they are adjusted for overlapping language and academic symptoms.

Conclusion

As a collection, these clinical metrics set the stage for further examination of potential linkages between attention deficits and language impairments.

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Phosphorylation of the amyloid β-peptide at Ser26 stabilizes oligomeric assembly and increases neurotoxicity

Abstract

Aggregation and toxicity of the amyloid β-peptide (Aβ) are considered as critical events in the initiation and progression of Alzheimer's disease (AD). Recent evidence indicated that soluble oligomeric Aβ assemblies exert pronounced toxicity, rather than larger fibrillar aggregates that deposit in the forms of extracellular plaques. While some rare mutations in the Aβ sequence that cause early-onset AD promote the oligomerization, molecular mechanisms that induce the formation or stabilization of oligomers of the wild-type Aβ remain unclear. Here, we identified an Aβ variant phosphorylated at Ser26 residue (pSer26Aβ) in transgenic mouse models of AD and in human brain that shows contrasting spatio-temporal distribution as compared to non-phosphorylated Aβ (npAβ) or other modified Aβ species. pSer26Aβ is particularly abundant in intraneuronal deposits at very early stages of AD, but much less in extracellular plaques. pSer26Aβ assembles into a specific oligomeric form that does not proceed further into larger fibrillar aggregates, and accumulates in characteristic intracellular compartments of granulovacuolar degeneration together with TDP-43 and phosphorylated tau. Importantly, pSer26Aβ oligomers exert increased toxicity in human neurons as compared to other known Aβ species. Thus, pSer26Aβ could represent a critical species in the neurodegeneration during AD pathogenesis.

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The Role of Vascular Imaging in the Initial Assessment of Patients with Acute Ischemic Stroke

Abstract

Over the last few years, improvement in radiological imaging and treatment has changed the management of acute ischemic stroke. We have made significant advances in not only the imaging modalities themselves but also in identifying imaging parameters that can help us predict patient outcomes with both intravascular thrombolysis and endovascular thrombectomy. In this review, we describe the added utility of baseline vascular imaging including computed tomography angiography and magnetic resonance angiography in the diagnosis and management of patients with acute ischemic stroke. We focus on information these imaging modalities provide on clot characteristics, tissue state, collateral status, and endovascular planning. We also highlight the benefits of newer imaging modalities like dynamic computed tomography angiography (CTA) and multi-phase CTA. Lastly, we also describe some of the disadvantages of vascular imaging in ischemic stroke.

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Cortical Reorganisation during a 30-Week Tinnitus Treatment Program

by Catherine M. McMahon, Ronny K. Ibrahim, Ankit Mathur

Subjective tinnitus is characterised by the conscious perception of a phantom sound. Previous studies have shown that individuals with chronic tinnitus have disrupted sound-evoked cortical tonotopic maps, time-shifted evoked auditory responses, and altered oscillatory cortical activity. The main objectives of this study were to: (i) compare sound-evoked brain responses and cortical tonotopic maps in individuals with bilateral tinnitus and those without tinnitus; and (ii) investigate whether changes in these sound-evoked responses occur with amelioration of the tinnitus percept during a 30-week tinnitus treatment program. Magnetoencephalography (MEG) recordings of 12 bilateral tinnitus participants and 10 control normal-hearing subjects reporting no tinnitus were recorded at baseline, using 500 Hz, 1000 Hz, 2000 Hz, and 4000 Hz tones presented monaurally at 70 dBSPL through insert tube phones. For the tinnitus participants, MEG recordings were obtained at 5-, 10-, 20- and 30- week time points during tinnitus treatment. Results for the 500 Hz and 1000 Hz sources (where hearing thresholds were within normal limits for all participants) showed that the tinnitus participants had a significantly larger and more anteriorly located source strengths when compared to the non-tinnitus participants. During the 30-week tinnitus treatment, the participants' 500 Hz and 1000 Hz source strengths remained higher than the non-tinnitus participants; however, the source locations shifted towards the direction recorded from the non-tinnitus control group. Further, in the left hemisphere, there was a time-shifted association between the trajectory of change of the individual's objective (source strength and anterior-posterior source location) and subjective measures (using tinnitus reaction questionnaire, TRQ). The differences in source strength between the two groups suggest that individuals with tinnitus have enhanced central gain which is not significantly influenced by the tinnitus treatment, and may result from the hearing loss per se. On the other hand, the shifts in the tonotopic map towards the non-tinnitus participants' source location suggests that the tinnitus treatment might reduce the disruptions in the map, presumably produced by the tinnitus percept directly or indirectly. Further, the similarity in the trajectory of change across the objective and subjective parameters after time-shifting the perceptual changes by 5 weeks suggests that during or following treatment, perceptual changes in the tinnitus percept may precede neurophysiological changes. Subgroup analyses conducted by magnitude of hearing loss suggest that there were no differences in the 500 Hz and 1000 Hz source strength amplitudes for the mild-moderate compared with the mild-severe hearing loss subgroup, although the mean source strength was consistently higher for the mild-severe subgroup. Further, the mild-severe subgroup had 500 Hz and 1000 Hz source locations located more anteriorly (i.e., more disrupted compared to the control group) compared to the mild-moderate group, although this was trending towards significance only for the 500Hz left hemisphere source. While the small numbers of participants within the subgroup analyses reduce the statistical power, this study suggests that those with greater magnitudes of hearing loss show greater cortical disruptions with tinnitus and that tinnitus treatment appears to reduce the tonotopic map disruptions but not the source strength (or central gain).

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Prosody and Semantics Are Separate but Not Separable Channels in the Perception of Emotional Speech: Test for Rating of Emotions in Speech

Purpose
Our aim is to explore the complex interplay of prosody (tone of speech) and semantics (verbal content) in the perception of discrete emotions in speech. Method
We implement a novel tool, the Test for Rating of Emotions in Speech. Eighty native English speakers were presented with spoken sentences made of different combinations of 5 discrete emotions (anger, fear, happiness, sadness, and neutral) presented in prosody and semantics. Listeners were asked to rate the sentence as a whole, integrating both speech channels, or to focus on one channel only (prosody or semantics). Results
We observed supremacy of congruency, failure of selective attention, and prosodic dominance. Supremacy of congruency means that a sentence that presents the same emotion in both speech channels was rated highest; failure of selective attention means that listeners were unable to selectively attend to one channel when instructed; and prosodic dominance means that prosodic information plays a larger role than semantics in processing emotional speech. Conclusions
Emotional prosody and semantics are separate but not separable channels, and it is difficult to perceive one without the influence of the other. Our findings indicate that the Test for Rating of Emotions in Speech can reveal specific aspects in the processing of emotional speech and may in the future prove useful for understanding emotion-processing deficits in individuals with pathologies.

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Epidemiologic Research on Malformations Associated with Cleft Lip and Cleft Palate in Japan

by Hiroshi Koga, Koichi Iida, Tomoki Maeda, Mizuho Takahashi, Naoki Fukushima, Terufumi Goshi

To investigate malformations associated with cleft lip and cleft palate, we conducted surveys at neonatal intensive care units (NICUs) and other non-NICU facilities and to determine whether there are differences among facilities. The regional survey investigated NICU facilities located in Oita Prefecture, including 92 patients with cleft lip and palate (CLP) or cleft palate (CP) that occurred between 2004 and 2013, and the national survey investigated oral surgery, plastic surgery, and obstetrics and gynecology facilities located in Japan, including 16,452 patients with cleft lip (CL), CLP, or CP that occurred since 2000. The incidence per 10,000 births was 4.2, 6.2, and 2.8 for CL, CLP, and CP, respectively, according to the national survey, and 6.3 and 2.9 for CLP and CP, respectively according to the regional survey. These results indicated comparable incidences between the two surveys. In contrast, when the survey results on malformations associated with CLP and CP according to the ICD-10 classification were compared between the national survey conducted at oral surgery or plastic surgery facilities and the regional survey conducted at NICU facilities, the occurrence of associated malformations was 19.8% vs. 41.3% for any types of associated malformation, 6.8% vs. 21.7% for congenital heart disease, and 0.5% vs. 16.3% for chromosomal abnormalities. These results indicated that the incidences of all of these associated malformations were significantly greater in the survey conducted at NICU facilities and similar to the findings from international epidemiological surveys. When comparing the survey conducted at obstetrics facilities vs. NICU facilities, the occurrence of associated malformations was similar results as above. The incidence of CLP and CP was not different between surveys conducted at NICU facilities vs. non-NICU facilities; however, when conducting surveys on associated malformations, it is possible to obtain accurate epidemiological data by investigating NICU facilities where detailed examinations are thoroughly performed.

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Markers, Models, and Measurement Error: Exploring the Links Between Attention Deficits and Language Impairments

Purpose
The empirical record regarding the expected co-occurrence of attention-deficit/hyperactivity disorder (ADHD) and specific language impairment is confusing and contradictory. A research plan is presented that has the potential to untangle links between these 2 common neurodevelopmental disorders. Method
Data from completed and ongoing research projects examining the relative value of different clinical markers for separating cases of specific language impairment from ADHD are presented. Results
The best option for measuring core language impairments in a manner that does not potentially penalize individuals with ADHD is to focus assessment on key grammatical and verbal memory skills. Likewise, assessment of ADHD symptoms through standardized informant rating scales is optimized when they are adjusted for overlapping language and academic symptoms. Conclusion
As a collection, these clinical metrics set the stage for further examination of potential linkages between attention deficits and language impairments.

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Prosody and Semantics Are Separate but Not Separable Channels in the Perception of Emotional Speech: Test for Rating of Emotions in Speech

Purpose
Our aim is to explore the complex interplay of prosody (tone of speech) and semantics (verbal content) in the perception of discrete emotions in speech. Method
We implement a novel tool, the Test for Rating of Emotions in Speech. Eighty native English speakers were presented with spoken sentences made of different combinations of 5 discrete emotions (anger, fear, happiness, sadness, and neutral) presented in prosody and semantics. Listeners were asked to rate the sentence as a whole, integrating both speech channels, or to focus on one channel only (prosody or semantics). Results
We observed supremacy of congruency, failure of selective attention, and prosodic dominance. Supremacy of congruency means that a sentence that presents the same emotion in both speech channels was rated highest; failure of selective attention means that listeners were unable to selectively attend to one channel when instructed; and prosodic dominance means that prosodic information plays a larger role than semantics in processing emotional speech. Conclusions
Emotional prosody and semantics are separate but not separable channels, and it is difficult to perceive one without the influence of the other. Our findings indicate that the Test for Rating of Emotions in Speech can reveal specific aspects in the processing of emotional speech and may in the future prove useful for understanding emotion-processing deficits in individuals with pathologies.

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Epidemiologic Research on Malformations Associated with Cleft Lip and Cleft Palate in Japan

by Hiroshi Koga, Koichi Iida, Tomoki Maeda, Mizuho Takahashi, Naoki Fukushima, Terufumi Goshi

To investigate malformations associated with cleft lip and cleft palate, we conducted surveys at neonatal intensive care units (NICUs) and other non-NICU facilities and to determine whether there are differences among facilities. The regional survey investigated NICU facilities located in Oita Prefecture, including 92 patients with cleft lip and palate (CLP) or cleft palate (CP) that occurred between 2004 and 2013, and the national survey investigated oral surgery, plastic surgery, and obstetrics and gynecology facilities located in Japan, including 16,452 patients with cleft lip (CL), CLP, or CP that occurred since 2000. The incidence per 10,000 births was 4.2, 6.2, and 2.8 for CL, CLP, and CP, respectively, according to the national survey, and 6.3 and 2.9 for CLP and CP, respectively according to the regional survey. These results indicated comparable incidences between the two surveys. In contrast, when the survey results on malformations associated with CLP and CP according to the ICD-10 classification were compared between the national survey conducted at oral surgery or plastic surgery facilities and the regional survey conducted at NICU facilities, the occurrence of associated malformations was 19.8% vs. 41.3% for any types of associated malformation, 6.8% vs. 21.7% for congenital heart disease, and 0.5% vs. 16.3% for chromosomal abnormalities. These results indicated that the incidences of all of these associated malformations were significantly greater in the survey conducted at NICU facilities and similar to the findings from international epidemiological surveys. When comparing the survey conducted at obstetrics facilities vs. NICU facilities, the occurrence of associated malformations was similar results as above. The incidence of CLP and CP was not different between surveys conducted at NICU facilities vs. non-NICU facilities; however, when conducting surveys on associated malformations, it is possible to obtain accurate epidemiological data by investigating NICU facilities where detailed examinations are thoroughly performed.

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Markers, Models, and Measurement Error: Exploring the Links Between Attention Deficits and Language Impairments

Purpose
The empirical record regarding the expected co-occurrence of attention-deficit/hyperactivity disorder (ADHD) and specific language impairment is confusing and contradictory. A research plan is presented that has the potential to untangle links between these 2 common neurodevelopmental disorders. Method
Data from completed and ongoing research projects examining the relative value of different clinical markers for separating cases of specific language impairment from ADHD are presented. Results
The best option for measuring core language impairments in a manner that does not potentially penalize individuals with ADHD is to focus assessment on key grammatical and verbal memory skills. Likewise, assessment of ADHD symptoms through standardized informant rating scales is optimized when they are adjusted for overlapping language and academic symptoms. Conclusion
As a collection, these clinical metrics set the stage for further examination of potential linkages between attention deficits and language impairments.

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A prospective investigation of predictive parameters for post-surgical recurrences in sinonasal polyposis

Abstract

Even after appropriate surgical therapy, a significant number of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) experience recurrences. The end-point of this prospective study was to apply univariate and multivariate statistical models to identify clinical, pathological, and laboratory variables that could predict CRSwNP recurrence after endoscopic sinus surgery. The study enrolled 143 patients between 2010 and 2013, who were all treated by the same surgeon for CRSwNP. Twenty-one patients developed recurrent polyposis. The recurrence rate was significantly higher for the eosinophilic than for the non-eosinophilic type (p = 0.020). Among the patients who developed a recurrence, the disease-free interval was significantly shorter for those with eosinophilic-type polyposis (p = 0.003). Univariate statistical analysis disclosed significant associations between CRSwNP recurrence and age (p = 0.035), allergy (p = 0.014), and eosinophilic granulomatosis with polyangiitis (p = 0.01). The multivariate model showed that only histological evidence of the eosinophilic type of CRSwNP retained an independent prognostic significance in relation to recurrent polyposis (p = 0.033). Judging from our results, it is reasonable to consider both stricter follow-up protocols and postoperative adjuvant medical treatments for patients with a histological diagnosis of eosinophilic-type CRSwNP.

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First results of Endonasal dilatation of the Eustachian tube (EET) in patients with chronic obstructive tube dysfunction

Abstract

For years, several surgical and non-surgical therapeutic strategies in Eustachian tube dysfunction have been described. The Endonasal dilatation of the Eustachian tube (EET) utilising a balloon catheter is a feasible option in patients with symptoms of chronic obstructive Eustachian tube dysfunction. However, long-term results in a large series are missing. In a prospective case series, 217 patients (342 cases) with symptoms of chronic Eustachian tube dysfunction underwent uni- or bilateral EET at the ENT Department of the University of Hamburg, Germany, between September 2010 and April 2013. A tube score consisting of the type of tympanogram and the R value of the tubomanometry was used to evaluate pre- and postoperative tube function. All patients underwent follow-up with a post-operative interval of 3–12 months. The mean value of the pre-treatment tube score was 2.23 ± 1.147 and significantly improved to 2.68 ± 1.011 1 year after EET. There was a significant increase in the tube score during follow-up. The co-variables time period, tympanoplasty and pressure range showed a significant impact on the tube score. EET is a minimally invasive and effective treatment of chronic obstructive tube dysfunction. It is a safe procedure without causing significant complications. Nevertheless, long-term results of larger, placebo-controlled multicentre studies are needed to confirm its effectiveness.

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Paraneoplastic syndromes in patients with laryngeal neuroendocrine carcinomas: clinical manifestations and prognostic significance

Abstract

Paraneoplastic syndromes are associated with a variety of malignant neoplasms and are systemic and non-metastatic manifestations that develop in a minority of cancer patients. This review examines all published cases of paraneoplastic syndromes associated with neuroendocrine carcinomas of the larynx. There are a total of ten patients reported with paraneoplastic syndromes associated with laryngeal neuroendocrine carcinomas in the literature. Of these, nine died and the tenth is alive with liver metastases. There were five cases of small-cell neuroendocrine carcinoma, four cases of moderately differentiated neuroendocrine carcinoma, and one case of well-differentiated neuroendocrine carcinoma associated with paraneoplastic syndromes. As these syndromes have significant clinical relevance, physicians should be aware of the possible presence of paraneoplastic syndromes in the diagnostic process of patients with neuroendocrine carcinoma of the larynx.

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Recurrent neck lesions secondary to pyriform sinus fistula

Abstract

Recurrent neck lesions associated with third or fourth branchial arch fistula are much less common than those of second arch and usually present with acute suppurative thyroiditis or neck abscess. Our aim is to describe clinical features, management and treatment outcomes of 64 cases of congenital pyriform sinus fistula (PSF). Medical record of these 64 patients (33 males, 31 females) treated at the First Affiliated Hospital of Zhengzhou University from 2011 to 2014 were reviewed. The patients comprised 33 males and 31 females, and their ages ranged from 18 months to 47 years (median 10 years, mean 12.7 years). Neck abscess and recurrent infection was the mode of presentation in 37 cases (57.8 %), 4 patients (6.3 %) presented with acute suppurative thyroiditis, neck mass was the mode of presentation in 17 cases (26.6 %), 2 patients (3.1 %) presented with neck mass with respiratory distress, and cutaneous discharging fistula was the mode of presentation in 1 cases (1.6 %). The remaining 3 patients (4.7 %) presented with cutaneous discharging fistula with neck infection. Investigations performed include barium swallow, CT scan, and ultrasound which were useful in delineating PSF tract preoperatively. Barium swallow was taken as the gold standard for diagnosis. Our patients were treated by fistulectomy with hemithyroidectomy, fistulectomy, fistulectomy with endoscopic electric cauterization, endoscopic electric cauterization or endoscopic coblation cauterization, respectively. Histopathologic examination of the surgical specimens revealed that they were lined with ciliated epithelium, stratified cuboid epithelium with chronic inflammatory cell infiltration and fibrosis. Voice hoarseness occurred after operation in seven patients, but disappeared 1 week later. PSF recurred in 6 patients, 4 of them were cured by a successful re-excision. One patient was cured by successful endoscopic electric cauterization. The other 1 has remained asymptomatic for 5 months. In our series, mean follow-up period was 13.3 months and median follow-up period was 12.5 months (range 2–40 months). Presence of congenital PSF should be suspected when intra-thyroidal abscess formation occurs as the gland is resistant to infection. Strong clinical suspicion, barium swallow study, CT scan and ultrasound are the key to diagnosis. Both fistulectomy with hemithyroidectomy and endoscopic treatment have comparable success rate. Endoscopic coblation cauterization may prove a useful and equally effective method of treatment for PSF in future.

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The new issue is now available.The Japan Journal of Logopedics and Phoniatrics

The Japan Journal of Logopedics and Phoniatrics

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Preparation and characterization of acetylated starch nanoparticles as drug carrier: Ciprofloxacin as a model

Publication date: June 2016
Source:International Journal of Biological Macromolecules, Volume 87
Author(s): Seyed Heydar Mahmoudi Najafi, Maryam Baghaie, Alireza Ashori
The objective of this study was to characterize in-vitro the potential of acetylated corn starch (ACS) particles as a matrix for the delivery of ciprofloxacin (CFx). ACS was successfully synthesized and optimized by the reaction of native corn starch using acetic anhydride and acetic acid with low and high degrees of substitution (DS). The nanoprecipitation method was applied for the formation of the ACS-based nanoparticles, by the dropwise addition of water to acetone solution of ACS under stirring. The effects of acetylation and nanoprecipitation on the morphology and granular structure of ACS samples were examined by the FT-IR, XRD, DSL and SEM techniques. The efficiency of CFx loading was also evaluated via encapsulation efficiency (EE) in ACS nanoparticles. The average degree of acetyl substitution per glucose residue of corn starch was 0.33, 2.00, and 2.66. The nanoparticles size of the ACS and ACS-loaded with CFx were measured and analyzed relative to the solvent:non-solvent ratio. Based on the results, ACS nanoparticles with DS of 2.00 and water:acetone of 3:1 had 312nm diameter. Increasing DS in starch acetate led to increase in the EE from 67.7 to 89.1% and with increasing ratio of water/acetone from 1:1 to 3:1, the EE raised from 48.5 to 89.1%. X-ray diffraction indicated that A-type pattern of native starch was completely transformed into the V-type pattern of acetylated starch. The scanning electron microscopy showed that the different sizes of pores formed on the acetylated starch granules were utterly converted into the uniform-sized spherical nanoparticles after the nanoprecipitation.

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The new issue is now available.The Japanese Journal of Gastroenterological Surgery

Vol.49 No.2

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Crystallographic studies of the complex of human HINT1 protein with a non-hydrolyzable analog of Ap4A

Publication date: June 2016
Source:International Journal of Biological Macromolecules, Volume 87
Author(s): Rafał Dolot, Renata Kaczmarek, Aleksandra Sęda, Agnieszka Krakowiak, Janina Baraniak, Barbara Nawrot
Histidine triad nucleotide-binding protein 1 (HINT1) represents the most ancient and widespread branch in the histidine triad proteins superfamily. HINT1 plays an important role in various biological processes, and it has been found in many species. Here, we report the first structure (at a 2.34Å resolution) of a complex of human HINT1 with a non-hydrolyzable analog of an Ap4A dinucleotide, containing bis-phosphorothioated glycerol mimicking a polyphosphate chain, obtained from a primitive monoclinic space group P21 crystal. In addition, the apo form of hHINT1 at the space group P21 refined to 1.92Å is reported for comparative studies.

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Effect of drying and loading methods on the release behavior of ciprofloxacin from starch nanoparticles

Publication date: June 2016
Source:International Journal of Biological Macromolecules, Volume 87
Author(s): Aimin Shi, Dong Li, Hongzhi Liu, Benu Adhikari, Qiang Wang
Drug loading into and release from starch nanoparticles (StNPs), one kind of novel biological macromolecule, were investigated. Two drying methods (spray and vacuum freeze drying) and drug loading methods (coating and adsorption) were used for evaluation. 40% (w/w) of ciprofloxacin was loaded using coating method while only 7% for adsorption method. Glass transition temperature (Tg) and melting point temperature (Tmp) of ciprofloxacin loaded starch nanoparticles varied from 40°C to 55°C and 125°C to 175°C. Particles using adsorption method had lower loading rate of ciprofloxacin, higher Tg, Tmp and release rate compared to using coating method. Tg and Tmp were not affected by these two drying methods. Release rate of ciprofloxacin was higher from freeze dried particles than from spray dried particles using coating method. For adsorption method, drying methods had not effect on the release rate. A double decay exponential model was able to fit the release data suitably well with coefficient of determination (R2)>0.97.

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The new issue is now available.Farumashia

Vol.52 No.2

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Cumulative Impact of HIV and Multiple Concurrent Human Papillomavirus Infections on the Risk of Cervical Dysplasia

Infection with HIV is known to increase the risk of cervical cancer. In addition, evidence suggests that concurrent infection with multiple human papillomavirus (HPV) genotypes increases the risk of cervical dysplasia more than infection with a single HPV genotype. However, the impact of the combination of HIV coinfection and presence of multiple concurrent HPV infections on the risk of cervical dysplasia is uncertain. We compared the results of HPV testing and Pap smears between HIV-infected and HIV-uninfected young women to assess the cumulative impact of these two conditions. We found that both HIV and the presence of multiple concurrent HPV infections are associated with increased risk of associated Pap smear abnormality and that the impact of these two risk factors may be additive.

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Comparison of outcome and interventional complication rate in patients with acute stroke treated with mechanical thrombectomy with and without bridging thrombolysis

Background

No randomized trial has investigated the effect of mechanical thrombectomy (MT) alone in patients with acute stroke. There are conflicting results as to whether prior intravenous thrombolysis (IVT) facilitates subsequent MT, and data in patients treated with MT alone owing to contraindications to IVT are limited.

Objective

To compare consecutive patients treated with MT alone or with preceding IVT in a large tertiary neurointerventional center, with special emphasis on contraindications to IVT.

Methods

Retrospective analysis of 283 consecutive patients with acute ischemic stroke treated with MT in a tertiary neurovascular center over 14 months. Data on characteristics of periprocedural times, recanalization rate, complications, and long-term functional outcome were collected prospectively.

Results

Information on prior IVT and functional outcome was available in 250 patients. Mean (SD) follow-up period was 5.7 (5.1) months and 105 (42%) patients received both IVT and MT. No significant differences were found in successful recanalization rates (Thrombolysis in Cerebral Infarction (TICI) 2b/3, 73.8% vs 73.1, p=0.952), complication rates, and long-term favorable outcome (modified Rankin Scale 0–2, 35.2% vs 40%, p=0.444) between patients receiving MT plus IVT and those receiving MT alone. A favorable outcome in patients directly treated with MT alone who were eligible for IVT was achieved in 48.2%. Thrombectomy was safe and resulted in a favorable outcome in 32% of patients with absolute contraindications to IVT.

Conclusions

Preceding use of IVT was not an independent predictor of favorable outcome in patients with acute stroke treated with MT and complication rates did not differ whether or not IVT was used. MT is safe and achieved a favorable outcome in one-third of patients with stroke ineligible for IVT.

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Einfluss der Ernährung bei Strahlen- und Radiochemotherapie

Zusammenfassung

Hintergrund

Patienten mit bösartigen Tumoren, die einer Strahlentherapie zugeführt werden, haben bereits primär häufig einen deutlich reduzierten Ernährungszustand. Dies kann tumor-, patienten- und therapiebedingt sein.

Material und Methoden

Darstellung der Ursachen der Malnutrition, insbesondere hinsichtlich der Strahlentherapie und Radiochemotherapie, und möglicher Therapieoptionen mit Hilfe von Literaturdaten sowie der Einbeziehung der aktuellen Leitlinien.

Ergebnisse

Insbesondere bei Patienten mit Tumoren der Kopf-Hals-Region und der Speiseröhre kommt es durch die Strahlentherapie/Radiochemotherapie zu einer Entzündung der Schleimhäute, einer Reduktion des Speichelflusses und einem Verlust der Geschmacksempfindung mit konsekutiver Dysphagie und Reduktion der Nahrungsaufnahme. Langfristig kann bei diesen Patienten eine Dysphagie durch eine Fibrose der Schluckmuskulatur ausgelöst werden; hinzu kommen Xerostomie und eine Verschlechterung des Zahnstatus. Durch verschiedene Methoden der Ernährungsbehandlung, diätetische Beratung, enterale Ernährung über Sonden, insbesondere der PEG, konnte in randomisierten Studien gezeigt werden, dass damit eine Verbesserung des Ernährungstatus und der Lebensqualität der Patienten erreicht werden kann. Die Patienten sollten bereits prätherapeutisch eine individuelle Ernährungsberatung erhalten; bei Bedarf sollte eine Sondenernährung zusätzlich erfolgen. Medikamentöse Maßnahmen zur Behandlung von Ernährungsstörungen während der Strahlentherapie haben sich in den letzten Jahren nicht durchgesetzt.

Schlussfolgerung

Durch eine konsequente Ernährungsberatung, der Verfügbarkeit enteraler Ernährung, der Verwendung von Sonden, insbesondere der PEG, können der Ernährungsstatus und die Lebensqualität von Tumorpatienten in der Regel während einer Strahlentherapie aufrechterhalten oder sogar verbessert werden.

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NIAC Seminar Series Lecture_Dr. Hongyu An, PhD

Dr. Hongyu An is an Associate Professor in the Department of Radiology at Washington University School of Medicine. Dr. An is currently working on a project to develop rapid, robust, accurate and non-invasive cerebral oxygenation measurements using MRI. She is also studying the effects of HIV infection and antiretroviral therapy on cerebral autoregulation. She is working with Dr. Zheng on a project to develop non-invasive MR imaging methods to quantify skeletal muscle oxygen uptake and efficiency in diabetic leg and foot. She is Co-Investigator on Dr. Ford's project studying the use of cerebral blood flow and oxygen extraction fraction as indicators of hemodynamic and metabolic stress, to stratify Stroke risk in Childhood Sickle Cell Disease.

Title: TBD

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Comparison of outcome and interventional complication rate in patients with acute stroke treated with mechanical thrombectomy with and without bridging thrombolysis

Background

No randomized trial has investigated the effect of mechanical thrombectomy (MT) alone in patients with acute stroke. There are conflicting results as to whether prior intravenous thrombolysis (IVT) facilitates subsequent MT, and data in patients treated with MT alone owing to contraindications to IVT are limited.

Objective

To compare consecutive patients treated with MT alone or with preceding IVT in a large tertiary neurointerventional center, with special emphasis on contraindications to IVT.

Methods

Retrospective analysis of 283 consecutive patients with acute ischemic stroke treated with MT in a tertiary neurovascular center over 14 months. Data on characteristics of periprocedural times, recanalization rate, complications, and long-term functional outcome were collected prospectively.

Results

Information on prior IVT and functional outcome was available in 250 patients. Mean (SD) follow-up period was 5.7 (5.1) months and 105 (42%) patients received both IVT and MT. No significant differences were found in successful recanalization rates (Thrombolysis in Cerebral Infarction (TICI) 2b/3, 73.8% vs 73.1, p=0.952), complication rates, and long-term favorable outcome (modified Rankin Scale 0–2, 35.2% vs 40%, p=0.444) between patients receiving MT plus IVT and those receiving MT alone. A favorable outcome in patients directly treated with MT alone who were eligible for IVT was achieved in 48.2%. Thrombectomy was safe and resulted in a favorable outcome in 32% of patients with absolute contraindications to IVT.

Conclusions

Preceding use of IVT was not an independent predictor of favorable outcome in patients with acute stroke treated with MT and complication rates did not differ whether or not IVT was used. MT is safe and achieved a favorable outcome in one-third of patients with stroke ineligible for IVT.

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Comparison of the effect of different modalities of physical exercise on functionality and anthropometric measurements in community-Dwelling older women

Publication date: Available online 21 February 2016
Source:Journal of Bodywork and Movement Therapies
Author(s): Ana Paula Sena Lomba Vasconcelos, Diogo Correia Cardozo, Alessandra Lamas Granero Lucchetti, Giancarlo Lucchetti
The present study aims to assess the effect of different modalities of physical exercises ("Functional Gymnastics"–FG,"Resistance Training"–RT and "Pilates combined with Hydrogymnastics"–PCH) on functional capacity and anthropometric measurements of 148 older women (60 years old or more). A comparative observational study was conducted. Functional and anthropometric measurements were assessed at baseline and after 16 weeks. All groups assessed showed significant changes between baseline and post-training. On the comparison of pre and post-training, differences in anthropometric measurements but not in functional test performance were found. The PCH had greater weight loss compared to the FG and RT, reduction in BMI compared to the FG and RT; reduction in waist compared to the FG and RT, and in hip compared to the RT. Although all groups improved, Pilates/Hydrogymnastics combination was more strongly associated with reductions in weight, BMI, waist and hip measurements but not functionality, than other modalities. These results highlight the role of combination physical exercise training in older women.



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The effect of kinesiology tape on knee proprioception in healthy subjects

Publication date: Available online 22 February 2016
Source:Journal of Bodywork and Movement Therapies
Author(s): Rui Torres, Raquel Trindade, Rui Soles Gonçalves
BackgroundKinesiology tape can improve athletic performance; however, due to cutaneous stimulation its application can have an influence on proprioception.ObjectivesTo determine the effects of kinesiology tape on knee proprioception applied to quadriceps, namely in the joint position sense (JPS) and in the threshold to detect passive movement (TTDPM), both immediately after and 24 hours after its application.MethodsThirty young healthy participants were randomly divided into experimental and control group. In the experimental group, a kinesiology tape on the quadriceps muscle was applied. The JPS and the TTDPM of the knee was assessed before, immediately after and 24 hours after the kinesiology tape intervention.ResultsNo significant differences were found in the assessment made before intervention. The Friedman Test showed that kinesiology tape had no influence on JPS in either group over time (p>0.05). However, the TTDPM decreased significantly immediately after and 24 hours after its application (p<0.05).



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A beneficial tumor microenvironment in oropharyngeal squamous cell carcinoma is characterized by a high T cell and low IL-17 + cell frequency

Abstract

Patients with HPV-positive oropharyngeal squamous cell carcinomas (OPSCCs) have a better prognosis than patients with non-HPV-induced OPSCC. The role of the immune response in this phenomenon is yet unclear. We studied the number of T cells, regulatory T cells (Tregs), T helper 17 (Th17) cells and IL-17+ non-T cells (mainly granulocytes) in matched HPV-positive and HPV-negative OPSCC cases (n = 162). Furthermore, the production of IFN-γ and IL-17 by tumor-infiltrating T cells was analyzed. The number of tumor-infiltrating T cells and Tregs was higher in HPV-positive than HPV-negative OPSCC (p < 0.0001). In contrast, HPV-negative OPSCC contained significantly higher numbers of IL-17+ non-T cells (p < 0.0001). Although a high number of intra-tumoral T cells showed a trend toward improved survival of all OPSCC patients, their prognostic effect in patients with a low number of intra-tumoral IL-17+ non-T cells was significant with regard to disease-specific (p = 0.033) and disease-free survival (p = 0.012). This suggests that a high frequency of IL-17+ non-T cells was related to a poor immune response, which was further supported by the observation that a high number of T cells was correlated with improved disease-free survival in the HPV-positive OPSCC (p = 0.008). In addition, we detected a minor Th17 cell population. However, T cells obtained from HPV-positive OPSCC produced significantly more IL-17 than those from HPV-negative tumors (p = 0.006). The improved prognosis of HPV-positive OPSCC is thus correlated with higher numbers of tumor-infiltrating T cells, more active Th17 cells and lower numbers of IL-17+ non-T cells.

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What we don’t know about osteoporosis

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Polymorphisms of the FTO and MTHFR genes and vascular, inflammatory and metabolic marker levels in postmenopausal women

Abstract

Objective

To determine the prevalence of three single nucleotide polymorphisms (SNPs) in postmenopausal women with and without the metabolic syndrome (METS) and to explore levels of circulating biomarkers of inflammation, vascular and metabolic dysfunction according to SNP genotypes.

Methods

DNA was extracted from the whole blood of 192 natural postmenopausal women (40 to 65 years) screened for the METS and tested for three gene SNPs related to obesity: the fat mass obesity (FTO: rs9939609) and the methylenetetrahydrofolate reductase (MTHFR: C677T and A1298C). Blood levels of angiopoietin, IL-8, sFASL, IL-6, TNF-α, sCD40L, PAI-1, u-PA, leptin, adiponectin, resistin, ghrelin, visfatin, adipsin and insulin were measured in a subgroup, with and without the METS, using multiplex technology (n = 100) and compared according to SNP genotypes.

Results

Genotype frequency of the three studied SNPs did not differ in relation to the presence of the METS. However, genotypes CT+TT (C677T) and AT (rs9939609) were more prevalent in women with high triglyceride levels. Pooled sub-analysis (n = 100) found that median sCD40L and visfatin levels were higher in women with genotypes AT+TT (rs9939609) as compared to AA (1178 vs. 937.0 pg/mL and 0.93 vs. 0.43 ng/mL, respectively, p < 0.05).

Conclusion

Two SNP genotypes related to obesity were more prevalent in women with abnormal triglyceride levels and two vascular and inflammatory serum markers were higher in relation to the rs9939609 SNP.

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Capnography best practices to improve patient handoff reports

By Kelly Grayson

Waveform capnography is an example of EMS as an early adopter of emerging technology. Often, in the hospital, recognition of the value of capnography has not spread beyond the confines of the anesthesiology department. As a patient advocate, use your knowledge of capnography to communicate important patient information to emergency department and intensive care unit staff.

You're picking up a patient in the ED, for a critical care transfer to the ICU at a Level I trauma center an hour away. Your patient has a subarachnoid hemorrhage, and was intubated in the ED and placed on a propofol infusion for sedation. Vent settings are assist/control mode, FiO2 of 40 percent, tidal volume of 650 mL, PEEP of 5.0 cm H20, and ventilatory rate of 16.

Your patient's hemodynamics are within acceptable parameters, and he seems to be tolerating the ventilator well, but when you attach your transport ventilator and end-tidal capnography adaptor, you see what you had suspected; your patient's ETCO2 is only 20 mm Hg, well below physiologic norms. A quick perusal of the patient's chart reveals arterial blood gases drawn five minutes after the patient was intubated an hour ago, and none taken since.

So when you hand off your patient to the accepting ICU staff at the trauma center, how do you justify your decision to adjust the vent settings to a more appropriate rate of 12 breaths/minute?

If you've ever dropped off an intubated, post-ROSC patient with an ETCO2 of 40 mm Hg at a ventilatory rate of 10 breaths/minute, only to see the ED staff immediately double your ventilatory rate under the erroneous assumption that all post-arrest patients are acidotic, or had an ED nurse look at you like you've sprouted a second head when you say you didn't administer a bronchodilator to a known asthma patient because both your capnograph and your stethoscope confirmed that there was no evidence of bronchospasm, then you know that not every ED staffer understands capnography like we do.

But if you'll follow these capnography documentation and handoff tips, you'll paint a much clearer picture of the patient's condition, and do a better job of explaining how capnography findings relate to that condition.

Which patients need capnography?
There is an old medical truism that states, «If you never check a temperature, you're going to miss a lot of fevers.» The same philosophy holds true for quantitative waveform capnography.

When we understand that capnography is the only real-time measure of the effectiveness of ventilation and a reliable indirect measure of perfusion, then that opens up an entire new world of applications. Simply put, we should be using capnography on any patient with significantly decreased level of consciousness, or any significant derangement in oxygenation, ventilation, or perfusion.

That adds up to a lot of patients.

Intubated and mechanically ventilated patients
Just like with normal breathing, ventilatory rate in mechanically ventilated patients has a direct bearing on ETCO2. When attaching a capnograph to an intubated, mechanically ventilated patient, there are four parameters to consider: initial ETCO2 reading, waveform morphology, ventilatory rate, and respiratory baseline (Phase I) measurement.

In patients with normal pulmonary physiology, end-tidal carbon dioxide (PetCO2) should be no more than 2-5 mm Hg less than arterial carbon dioxide (PaCO2), and is usually within 1 mm Hg of PaCO2 [1]. Document initial PetCO2 readings, and compare those to arterial blood gases, if any are available. Normal PaCO2 is 35-45 mm Hg, therefore PetCO2 would theoretically be 34-44 mm Hg, and should never be more than 5 mm Hg less than the arterial CO2 in patients with normal pulmonary physiology.

However, most intubated patients do not have normal pulmonary physiology, or they wouldn't have been intubated in the first place. Use caution in changing ventilator rate settings to titrate ventilations to a normal PetCO2 reading. If the patient has significant ventilation/perfusion (V/Q) mismatch due to pulmonary shunting, you risk hypoventilating the patient when titrating ventilations to PetCO2.

If the end-tidal gradient, P(a-et)CO2 is more than 10 mm Hg, a shunt exists, but it is impossible to determine this unless you are comparing capnography readings and arterial blood gases measured within the same time frame. When documenting a change in ventilator rate settings and why, be sure to include PaCO2 and PetCO2 and the time each was measured (ideally, within the same time frame), and the change in PetCO2 with the new settings.

Pay particular attention to the inspiratory baseline (Phase 1) in mechanically ventilated patients. Ideally, the baseline should be zero. If the baseline is above zero in a mechanically ventilated patient and the Beta angle is greater than 90 degrees, this is an indication that the patient is rebreathing carbon dioxide.

Incompetent inspiratory or expiratory valves or a depleted CO2 absorber may be the culprit. If your ventilator isn't flashing an alarm and a troubleshooting message, briefly ventilate the patient with a BVM on room air, and recheck the inspiratory baseline. If it returns to zero, you have a malfunctioning ventilator.

Sudden change in the capnography waveform (prolonged Phase III, increased Beta angle) and a decreased PetCO2 may indicate pulmonary embolus, pneumothorax, or migration of the tube into the right mainstem, resulting in single lung ventilation.

In patients with chest tubes, inability to maintain an alveolar plateau, with «stair step» Phase 0, may indicate occlusion of the chest tube [2,3].

Patients who have undergone neuromuscular blockade may exhibit inspiratory effort at a level too low to trigger the ventilator as the neuromuscular blockers wear off. This «curare cleft,» named after the first primitive neuromuscular blocker, presents as a miniscule notch in the alveolar plateau (Phase III).

When you notice curare clefts in your capnography waveform, you only have 2-3 minutes to re-administer the neuromuscular blockade before the patient comes out of paralysis.

Intra and post-arrest patients
During cardiopulmonary resuscitation, waveform capnography can serve a variety of valuable functions. As a prognostic indicator of resuscitation outcomes, PetCO2 that is consistently lower than 10 mm Hg despite adequate ventilation and effective chest compressions can be considered a criterion for termination of resuscitation efforts [4, 5]. If protocols dictate consultation with medical control before terminating resuscitation in the field, be sure to inform the physician that CO2 levels have been consistently less than 10 mm Hg, and include the PetCO2 reading at termination of resuscitation efforts in your documentation.

During resuscitation, effectiveness of chest compressions can be reflected in the capnography waveforms [6]. Diminishing PetCO2 can indicate compressor fatigue, or if there is a significant disparity in PetCO2 readings between rescuers, a flaw in one rescuer's compression technique.

A sudden increase in PetCO2 during resuscitation may indicate return of spontaneous circulation (ROSC), and often precedes a palpable peripheral pulse. This has been demonstrated in animal models as well as human cardiac arrest patients [7,8,9].

Always recheck and document PetCO2 after any major move in packaging and transport, and the PetCO2 at time of handoff in the Emergency Department. Titrate ventilation rate to a physiologically normal PetCO2 (35-45 mm Hg), and communicate the PetCO2 and rate required to achieve it to the ED staff at handoff.

Respiratory patients
Waveform capnography can be a useful monitoring parameter in asthma patients, and may help differentiate the wheezes of cardiac asthma from the obstructive bronchospasm characteristic of asthma and other obstructive pulmonary diseases. While wheezes may be present in early stages of acute pulmonary edema, the patients usually lack the characteristic «shark fin» waveform of acute bronchospasm.

While monitoring non-intubated respiratory patients, carefully monitor the inspiratory baseline, waveform morphology and PetCO2. Rising carbon dioxide readings may indicate respiratory fatigue. Elevated inspiratory baseline may indicate rebreathing of CO2, either from too low an oxygen flow rate, or from malfunction of the valve in a non-rebreather mask.

PetCO2 may be decreased in tachypneic patients with pulmonary embolus, but may be differentiated from hyperventilation syndrome by the presence of low SPO2 levels and lack of carpopedal spasms.

When handing off respiratory patients in the ED, saying «No shark fins were present,» or «CO2 waveforms were normal,» may be meaningless to staff unfamiliar with waveform capnography. Instead, put the information in context; provide a pre- and post-treatment PetCO2 reading just as you would a room air and post-treatment oxygen saturation, and say, «CO2 waveforms showed consistent alveolar emptying and no evidence of bronchospasm.»

Patients at risk of impaired perfusion
PetCO2 is an excellent non-invasive surrogate for measuring cardiac output. Since decreased PetCO2 levels often appear before frank hypotension, waveform capnography should be used on all patients at risk of impaired perfusion. In patients with risk of impaired perfusion, waveform morphology is not as important as the PetCO2.

In severe sepsis patients, decreased PetCO2 strongly correlates to elevated serum lactate levels, a reliable measure of metabolic stress. PetCO2 of less than 25 mm Hg is associated with serum lactate greater than 4 mmol/L, and these patients are at far greater risk of septic shock.

When handing off trauma patients or other patients at risk of hypoperfusion, inform the ED staff of current PetCO2 levels, and any post-treatment changes.

Patients at risk of CNS depression
Most of the sedatives and analgesics we administer can reduce respiratory drive, as can organic causes, trauma, and illicit drugs. Monitor PetCO2 in any patient with altered mental status, and be alert for hypoventilation. Re-administer naloxone if appropriate, or if the patient is arousable to verbal stimulus. The simple expedient of engaging your patient in conversation throughout transport can keep the patient from becoming somnolent and maintain PetCO2 at physiologically appropriate levels. If you administered naloxone, or inserted an invasive airway device for airway maintenance in the obtunded patient, document pre- and post-treatment PetCO2 and inform the ED staff of those readings.

Use these capnography practices to guide your patient care, paint a more comprehensive patient picture in your documentation, and better inform receiving hospital staff of critical information. As we better communicate capnography findings to hospital staff, more of them will begin to embrace the technology and value its findings.

References

1. Corbo J, Bijur P, Lahn M, Gallagher EJ. Concordance Between Capnography and Arterial Blood Gas Measurements of Carbon Dioxide in Acute Asthma. Annals of Emergency Medicine. Volume 46, Issue 4, October 2005, Pages 323–327.
2. What happens to PetCO2 When There Is a Pneumothorax
3. Capnograph Waveforms In the Mechanically Ventilated Patient
4. Ahrens T, Schallom L, Bettorf K, Ellner S, Hurt G, O'Mara V, Ludwig J, George W, Marino T, Shannon W. End-tidal Carbon Dioxide Measurements as a Prognostic Indicator of Outcome in Cardiac Arrest. American Journal of Critical Care. 2001 Nov;10(6):391-8.
5. Callaham M, Barton C. Prediction of outcome of cardiopulmonary resuscitation from end-tidal carbon dioxide concentration. Critical Care Medicine. 1990 Apr;18(4):358-62.
6. Morisaki H, Takino Y, Kobayashi H, Ando Y, Ichikizaki K. End-tidal Carbon Dioxide Concentration During Cardiopulmonary Resuscitation in Patients with Pre-hospital Cardiac Arrest. Masui. 1991 Jul;40(7):1048-51.
7. Berg RA, Henry C, Otto CW, Sanders AB, Kern KB, Hilwig RW, Ewy GA. Initial End-tidal CO2 Is Markedly Elevated During Cardiopulmonary Resuscitation After Asphyxial Cardiac Arrest. Pediatric Emergency Care. 1996 Aug;12(4):245-8.
8. Steedman DJ, Robertson CE. Measurement of End-tidal Carbon Dioxide Concentration During Cardiopulmonary Resuscitation. Archives of Emergency Medicine. 1990 Sep;7(3):129-34.
9. Falk JL, Rackow EC, Weil MH. End-tidal carbon dioxide concentration during cardiopulmonary resuscitation. New England Journal of Medicine. 1988 Mar 10;318(10):607-11.

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Epigenetic regulation in dental pulp inflammation

Abstract

Dental caries, trauma and other possible factors could lead to injury of the dental pulp. Dental infection could result in immune and inflammatory responses mediated by molecular and cellular events and tissue breakdown. The inflammatory response of dental pulp could be regulated by genetic and epigenetic events. Epigenetic modifications play a fundamental role in gene expression. The epigenetic events might play critical roles in the inflammatory process of dental pulp injury. Major epigenetic events include methylation and acetylation of histones and regulatory factors, DNA methylation, and small non-coding RNAs. Infections and other environmental factors have profound effects on epigenetic modifications and trigger diseases. Despite growing evidences of literatures addressing the role of epigenetics in the field of medicine and biology, very little is known about the epigenetic pathways involved in dental pulp inflammation. This review summarized the current knowledge about epigenetic mechanisms during dental pulp inflammation. Progress in studies of epigenetic alterations during inflammatory response would provide opportunities for the development of efficient medications of epigenetic therapy for pulpitis.

This article is protected by copyright. All rights reserved.

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NIAC Seminar Series Lecture_Dr. Hongyu An, PhD

Dr. Hongyu An is an Associate Professor in the Department of Radiology at Washington University School of Medicine.  Dr. An is currently working on a project to develop rapid, robust, accurate and non-invasive cerebral oxygenation measurements using MRI.  She is also studying the effects of HIV infection and antiretroviral therapy on cerebral autoregulation.  She is working with Dr. Zheng on a project to develop non-invasive MR imaging methods to quantify skeletal muscle oxygen uptake and efficiency in diabetic leg and foot.  She is Co-Investigator on Dr. Ford's project studying the use of cerebral blood flow and oxygen extraction fraction as indicators of hemodynamic and metabolic stress, to stratify Stroke risk in Childhood Sickle Cell Disease.

Title: TBD

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Isatis indigotica root polysaccharides as adjuvants for an inactivated rabies virus vaccine

Publication date: June 2016
Source:International Journal of Biological Macromolecules, Volume 87
Author(s): Weijiao Zhang, Xuexing Zheng, Nan Cheng, Weiwei Gai, Xianghong Xue, Yuxia Wang, Yuwei Gao, Junjie Shan, Songtao Yang, Xianzhu Xia
Adjuvants can enhance vaccine immunogenicity and induce long-term enhancement of immune responses. Thus, adjuvants are important for vaccine research. Polysaccharides isolated from select Chinese herbs have been demonstrated to possess various beneficial functions and excellent adjuvant abilities. In the present study, the polysaccharides IIP-A-1 and IIP-2 were isolated from Isatis indigotica root and compared with the common vaccine adjuvant aluminum hydroxide via intramuscular co-administration of inactivated rabies virus rCVS-11-G into mice. Blood was collected to determine virus neutralizing antibody (VNA) titers and B and T lymphocyte activation status. Inguinal lymph node samples were collected and used to measure B lymphocyte proliferation. Splenocytes were isolated, from which antigen-specific cellular immune responses were detected via ELISpot, ELISA and intracellular cytokine staining. The results revealed that both types of polysaccharides induce more rapid changes and higher VNA titers than aluminum hydroxide. Flow cytometry assays revealed that the polysaccharides activated more B lymphocytes in the lymph nodes and more B and T lymphocytes in the blood than aluminum hydroxide. Antigen-specific cellular immune responses showed that IIP-2 strongly induced T lymphocyte proliferation in the spleen and high levels of cytokine secretion from splenocytes, whereas aluminum hydroxide induced proliferation in only a small number of lymphocytes and the secretion of only small quantities of cytokines. Collectively, these data suggest that the polysaccharide IIP-2 exhibits excellent adjuvant activity and can enhance both cellular and humoral immunity.

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