Publication date: Available online 10 May 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Diane R. Gold, Gary Adamkiewicz, Syed Hasan Arshad, Juan C. Celedón, Martin D. Chapman, Ginger L. Chew, Donald N. Cook, Adnan Custovic, Ulrike Gehring, James E. Gern, Christine C. Johnson, Suzanne Kennedy, Petros Koutrakis, Brian Leaderer, Herman Mitchell, Augusto A. Litonjua, Geoffrey A. Mueller, George T. O'Connor, Dennis Ownby, Wanda Phipatanakul, Victoria Persky, Matthew S. Perzanowski, Clare D. Ramsey, Päivi M. Salo, Julie M. Schwaninger, Joanne E. Sordillo, Avrum Spira, Shakira F. Suglia, Alkis Togias, Darryl C. Zeldin, Elizabeth C. Matsui
Environmental exposures have been recognized as critical in the initiation and exacerbation of asthma, one of the most common chronic childhood diseases.The National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Environmental Health Sciences (NIEHS), National Heart, Lung, and Blood Institute (NHLBI), and Merck Childhood Asthma Network (MCAN) sponsored a joint workshop to discuss the current state of the science with respect to the indoor environment and its effects on the development and morbidity of childhood asthma. The workshop included U.S. and international experts with backgrounds in allergy/allergens, immunology, asthma, environmental health, environmental exposures and pollutants, epidemiology, public health, and bioinformatics. Workshop participants provided new insights into the biologic properties of indoor exposures, indoor exposure assessment and exposure reduction techniques. This informed a primary focus of the workshop-- to critically review trials and research relevant to the prevention or control of asthma through environmental intervention. The participants identified important limitations and gaps in the scientific methodologies and knowledge, and proposed and prioritized areas for future research. The group reviewed socioeconomic and structural challenges to changing environmental exposure and offered recommendations for creative study design to overcome these challenges in trials to improve asthma management. The recommendations of this workshop can serve as guidance for future research in the study of the indoor environment and on environmental interventions as they pertain to the prevention and management of asthma and airway allergies.
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<span class="paragraphSection"><div class="boxTitle">Abstract</div>Although it is clear that early language acquisition can be a target of <span style="font-style:italic;">CNTNAP2</span>, the pathway between gene and language is still largely unknown. This research focused on the mediation role of rapid auditory processing (RAP). We tested RAP at 6 months of age by the use of event-related potentials, as a mediator between common variants of the <span style="font-style:italic;">CNTNAP2</span> gene (rs7794745 and rs2710102) and 20-month-old language outcome in a prospective longitudinal study of 96 Italian infants. The mediation model examines the hypothesis that language outcome is explained by a sequence of effects involving RAP and <span style="font-style:italic;">CNTNAP2</span>. The ability to discriminate spectrotemporally complex auditory frequency changes at 6 months of age mediates the contribution of rs2710102 to expressive vocabulary at 20 months. The indirect effect revealed that rs2710102 C/C was associated with lower P3 amplitude in the right hemisphere, which, in turn, predicted poorer expressive vocabulary at 20 months of age. These findings add to a growing body of literature implicating RAP as a viable marker in genetic studies of language development. The results demonstrate a potential developmental cascade of effects, whereby <span style="font-style:italic;">CNTNAP2</span> drives RAP functioning that, in turn, contributes to early expressive outcome.</span>
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<span class="paragraphSection"><div class="boxTitle">Abstract</div>Direction selectivity (DS) of neuronal responses is fundamental for motion detection. With in vivo whole-cell voltage-clamp recordings from layer (L)4 neurons in the mouse visual cortex, we observed a strong correlation between DS and spatial asymmetry in the distribution of excitatory input strengths. This raises an interesting possibility that the latter may contribute to DS. The preferred direction of excitatory input was found from the stronger to weaker side of its spatial receptive field. A simple linear summation of asymmetrically distributed excitatory responses to stationary flash stimuli however failed to predict the correct directionality: it at best resulted in weak DS with preferred direction opposite to what was observed experimentally. Further studies with sequential 2 flash-bar stimulation revealed a short-term suppression of excitatory input evoked by the late bar. More importantly, the level of the suppression positively correlated with the relative amplitude of the early-bar response. Implementing this amplitude-dependent suppressive interaction can successfully predict DS of excitatory input. Our results suggest that via nonlinear temporal interactions, the spatial asymmetry can be transformed into differential temporal integration of inputs under opposite directional movements. This mechanism may contribute to the DS of excitatory inputs to L4 neurons.</span>
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<span class="paragraphSection"><div class="boxTitle">Abstract</div>Although whisker-related perception is based predominantly on local, near-instantaneous coding, global, intensive coding, which integrates the vibrotactile signal over time, has also been shown to play a role given appropriate behavioral conditions. Here, we study global coding in isolation by studying head-fixed rats that identified pulsatile stimuli differing in pulse frequency but not in pulse waveforms, thus abolishing perception based on local coding. We quantified time locking and spike counts as likely variables underpinning the 2 coding schemes. Both neurometric variables contained substantial stimulus information, carried even by spikes of single barrel cortex neurons. To elucidate which type of information is actually used by the rats, we systematically compared psychometric with neurometric sensitivity based on the 2 coding schemes. Neurometric performance was calculated by using a population-encoding model incorporating the properties of our recorded neuron sample. We found that sensitivity calculated from spike counts sampled over long periods (>1 s) matched the performance of rats better than the one carried by spikes time-locked to the stimulus. We conclude that spike counts are more relevant to tactile perception when instantaneous kinematic parameters are not available.</span>
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<span class="paragraphSection"><div class="boxTitle">Abstract</div>Corticosteroid stress hormones exert a profound impact on cognitive and emotional processes. Understanding the neuronal circuits that are altered by chronic stress is important for counteracting the detrimental effects of stress in a brain region- and cell type-specific manner. Using the chemogenetic tool, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), which enables the remote, noninvasive and long-lasting modulation of cellular activity and signal transduction in discrete neuronal populations in vivo, we sought to identify the specific pathways that play an essential role in stress responses. We found that prolonged severe stress induced the diminished glutamatergic projection from pyramidal neurons in prefrontal cortex (PFC) to GABAergic interneurons in basolateral amygdala (BLA), leading to the loss of feedforward inhibition and ensuing hyperexcitability of BLA principal neurons, which caused a variety of behavioral abnormalities. Activating PFC pyramidal neurons with hM3D(Gq) DREADD restored the functional connection between PFC and BLA in stressed animals, resulting in the rescue of recognition memory, normalization of locomotor activity and reduction of aggressive behaviors. Inhibiting BLA principal neurons directly with hM4D(Gi) DREADD also blocked BLA hyperactivity and aggressive behaviors in stressed animals. These results have offered an effective avenue to counteract the stress-induced disruption of circuitry homeostasis.</span>
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<span class="paragraphSection"><div class="boxTitle">Abstract</div>Snakes and conspecific faces are quickly and efficiently detected in primates. Because the medial prefrontal cortex (mPFC) has been implicated in attentional allocation to biologically relevant stimuli, we hypothesized that it might also be highly responsive to snakes and conspecific faces. In this study, neuronal responses in the monkey mPFC were recorded, while monkeys discriminated 8 categories of visual stimuli. Here, we show that the monkey mPFC neuronal responses to snakes and conspecific faces were unique. First, the ratios of the neurons that responded strongly to snakes and monkey faces were greater than those of the neurons that responded strongly to the other stimuli. Second, mPFC neurons responded stronger and faster to snakes and monkey faces than the other categories of stimuli. Third, neuronal responses to snakes were unaffected by low-pass filtering of the images. Finally, activity patterns of responsive mPFC neurons discriminated snakes from the other stimuli in the second 50 ms period and monkey faces in the third period after stimulus onset. These response features indicate that the mPFC processes fast and coarse visual information of snakes and monkey faces, and support the hypothesis that snakes and social environments have shaped the primate visual system over evolutionary time.</span>
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Adenotonsillectomy (AT) is the most commonly performed procedure for sleep disordered breathing (SDB) in pediatrics. However, 20-40% of patients will have persistent signs and symptoms of SDB after AT. Drug-induced sleep endoscopy (DISE) has the potential to individualize surgical treatments and avoid unnecessary or unsuccessful surgeries. The objective of this study was to determine the predictors of failure of DISE-directed adenoidectomy and/or tonsillectomy in otherwise healthy children with SDB.
We retrospectively reviewed a prospective database of children who presented with SDB. All patients underwent preoperative pulse oximetry (PO), followed by DISE with T ± A, The variables documented included demographics, ethnicity, co-morbidities, family history, McGill Oximetry Score (MOS) on PO, as well as findings of collapse and or obstruction on DISE and symptom resolution based on modified Pediatric Sleep Questionnaire (PSQ). The primary outcome was the independent predictors of treatment failure based on multivariate binary logistic regression.
Three hundred eighty-two patients satisfied the inclusion criteria. Based on post-operative modified PSQ, SDB resolved in 259 patients (68%), whereas 123 (32%) had persistent symptoms. On bivariate analysis, neuropsychiatric diagnosis (r = 0.286, p = 0.042), history of sleepwalking or enuresis (r = 0.103, p = 0.044), MOS (r = 0.123, p = 0.033), presence of DNS (r = 0.107, p = 0.036), and presence of laryngomalacia (r = 0.122, p = 0.017) all positively correlated with treatment failure. Small tonsil size on DISE correlated with treatment failure (r = −0.180, p < 0.001). Multivariate analysis identified age greater than 7 years (OR = 1.799, [95% CI 1.040–3.139], p = 0.039), obesity (OR = 2.032, [95% CI 1.043–3.997], p = 0.040), chronic rhinitis (OR = 1.334, [95% CI 1.047–1.716], p = 0.025), deviated nasal septum (OR = 1.745, [95% CI 1.062–2.898], p = 0.031) and tonsil size (OR = 0.575, [95% CI 0.429–0.772], p < 0.01) as independent predictors of treatment failure.
Obese, asthmatic, and children older than seven years are at increased risk of treatment failure after DISE-directed AT. Several DISE findings can independently predict AT failure, including tonsil size, degree of chronic rhinitis, and the presence of a deviated nasal septum, and can be addressed at a second stage. Further research is needed into the role of DISE in surgically naïve patients with SDB, and to compare DISE-directed surgery with the current standard of care.
Research productivity is an important component of the CanMEDS Scholar role and is an accreditation requirement of Canadian Otolaryngology training programs. Our objective was to determine if an association exists between publication rates before and during Otolaryngology residency.
We obtained the names for all certified Canadian Otolaryngologists who graduated between 1998 and 2013 inclusive, and conducted a Medline search for all of their publications. Otolaryngologists were subgrouped based on year of residency graduation and the number of articles published pre-residency and during residency (0 or ≥1). Chi-squared analyses were used to evaluate whether publications pre-residency and year of graduation were associated with publications during residency.
We obtained data for 312 Canadian Otolaryngologists. Of those 312 graduates, 46 (14.7%) had no identifiable publications on PubMed and were excluded from the final data analysis. Otolaryngology residents had a mean 0.65 (95% CI 0.50-0.80) publications before residency and 3.35 (95% CI 2.90-3.80) publications during residency. Between 1998 and 2013, mean publication rates before and during residency both increased significantly (R 2 = 0.594 and R 2 = 0.759, respectively), whereas publication rates after residency graduation has stagnated (R 2 = 0.023). The odds of publishing during residency was 5.85 times higher (95% CI 2.69-12.71) if a resident published prior to residency (p < 0.0001). The Spearman correlation coefficient between publications before and during residency is 0.472 (p < 0.0001).
Residents who publish at least one paper before residency are nearly six times as likely to publish during residency than those who did not publish before residency. These findings may help guide Otolaryngology program selection committees in ranking the best CaRMS candidates.
The inserted cochlear implanted electrode is covered at the site of the round window or cochleostomy to prevent infections and leakage. In a surgically hearing preservational concept, low intracochlear pressure changes are of high importance. The aim of this study was to observe intracochlear pressure changes due to different sealing techniques in a cochlear model.
Cochlear implant electrode insertions were performed in an artifical cochlear model and the intracochlear pressure changes were recorded in parallel with a micro-pressure sensor positioned in the apical region of the cochlea model to follow the maximum amplitude of intracochlear pressure. Four different sealing conditions were compared: 1) overlay, 2) overlay with fascia pushed in, 3) donut-like fascia ring, 4) donut-like fascia ring pushed in.
We found statistically significant differences in the occurrence of maximum amplitude of intracochlear pressure peak changes related to sealing procedure comparing the different techniques. While the lowest amplitude changes could be observed for the overlay technique (0.14 mmHg ± 0.06) the highest values could be observed for the donut-like pushed in technique (1.79 mmHg ± 0.69).
Sealing the electrode inserted cochlea can lead to significant intracochlear pressure changes. Pushing in of the sealing tissue cannot be recommended.
We aim to characterize the workup received by and identify any delays to diagnosis or treatment in patients referred to a tertiary cancer centre with the diagnosis of squamous cell carcinoma in neck node(s) and no identifiable primary (SCCNIP).
Over 1 year, 68 patients were initially referred to the Head and Neck clinic with a label of "primary unknown". After extensive workup, 29 of the 68 patients were found to have pathologically confirmed SCCNIP. For these 29 patients, imaging tests, biopsies, examinations and times to treatment were reviewed and compared to 145 patients referred for known primaries.
In 21/29 (72%) patients, ultrasound was ordered prior to biopsy or referral. After referral, the first imaging test used was CT neck in 28 patients and PET/CT in 1 patient.
Median time from referral to primary identification (n = 23) or workup completion (n = 6) were 16 (range: 0-48) and 36 (17-82) days respectively. Median time from referral to treatment was 55 (27-90; n = 26) days and was longer than those referred for known primaries (48 days; 20-162; p < 0.001). Across all patients, median time between first diagnostic imaging test and pathologic diagnosis were 20.5 and -8.0 days (p < 0.0001) in patients receiving ultrasound and CT, respectively.
In our cohort, delays to management were linked to community use of ultrasound and scheduling of both CT and PET/CT after thorough head and neck examination in patients with SCCNIP.
Squamous cell carcinomas (SCCs) are the most prevalent malignant tumours within the head and neck. Evidence exists that distinct genes are differentially regulated in SCCs of the oral cavity compared to other head and neck regions. Given this background, the aim of this study was to investigate whether such tumour site-specific gene expression can also be observed in different localizations within the oral cavity.
Using tissue microarrays (TMAs), we investigated 76 SCCs of the floor of the mouth, 49 SCCs of the tongue and 68 SCCs of other anatomic regions within the oral cavity. The expression of 17 genes involved in cell cycle and growth control (p16, p21, p27, p53, cyclin D1, EGFR, c-kit, bcl-6), cell adhesion (alpha-, beta-, and gamma-catenin), and apoptosis/stress response genes (Hif-1-alpha, Glut 1, CA IX, caspase, hsp70, XIAP) were investigated by means of immunohistochemistry. The data were subjected to chi2, interdependency and Kaplan-Meier analysis.
Our study suggests a remote difference in the site-specific gene expression patterns of oral cancer. X-linked inhibitor of apoptosis (XIAP) showed a significantly higher expression (p <0.05) in SCCs of the floor of the mouth compared to SCCs of the tongue and other locations within the oral cavity. The increased XIAP expression was further associated with significantly decreased overall survival in all cases of SCCs of the oral cavity (p <0.05). Expression levels of p53, CA IX, beta-catenin, Hif-1-alpha, and c-kit were also observed to be inversely related between SCCs of the floor of the mouth and those of the tongue respectively, although these differences did not reach statistical significance. Overall and event-free survival did not differ in patients with T1/T2/N0 SCCs according to tumour localization.
In summary, the protein expression patterns of SCCs of the oral cavity suggest the existence of a molecular and morphological spectrum of SCCs in the oral cavity. In particular the expression pattern of XIAP indicates distinct gene expression patterns between carcinomas of the floor of the mouth and oral tongue cancer. Further studies are needed to identify possible tumour site-specific factors that influence patient prognosis and management.
This was a diagnostic accuracy study to develop an algorithm based on administrative database codes that identifies patients with Chronic Rhinosinusitis (CRS) who have endoscopic sinus surgery (ESS).
From January 1st, 2011 to December 31st, 2012, a chart review was performed for all hospital-identified ESS surgical encounters. The reference standard was developed as follows: cases were assigned to encounters in which ESS was performed for Otolaryngologist-diagnosed CRS; all other chart review encounters, and all other hospital surgical encounters during the timeframe were controls. Algorithm development was based on International Classification of Diseases, version 10 (ICD-10) diagnostic codes and Canadian Classification of Health Interventions (CCI) procedural codes. Internal model validation was performed with a similar chart review for all model-identified cases and 200 randomly selected controls during the following year.
During the study period, 347 cases and 185,007 controls were identified. The predictive model assigned cases to all encounters that contained at least one CRS ICD-10 diagnostic code and at least one ESS CCI procedural code. Compared to the reference standard, the algorithm was very accurate: sensitivity 96.0% (95%CI 93.2–97.7), specificity 100% (95% CI 99.9–100), and positive predictive value 95.4% (95%CI 92.5–97.3). Internal validation using chart review for the following year revealed similar accuracy: sensitivity 98.9% (95%CI 95.8–99.8), specificity 97.1% (95%CI 93.4–98.8), and positive predictive value 96.9% (95%CI 93.0–99.8).
A simple model based on administrative database codes accurately identified ESS-CRS encounters. This model can be used in population-based cohorts to study longitudinal outcomes for the ESS-CRS population.
This study surveyed non-United States maxillofacial prosthodontists (MFP) to determine their practice profile and rationale for pursuing an MFP career.
Email addresses for the MFP were obtained from the International Society for Maxillofacial Rehabilitation, American Academy of Maxillofacial Prosthetics, and International Academy for Oral Facial Rehabilitation. Emails with a link to the electronic survey program were sent to each participant. Chi-square and Mann–Whitney-U tests were used to investigate the influence of formal MFP training on professional activities and type of treatments provided.
One hundred twelve respondents (response rate 39%) from 33 nationalities returned the survey. The top three reasons for pursuing an MFP career were personal satisfaction, prosthodontics residency exposure, and mentorship. The predominant employment setting was affiliation with a university (77%). There were significant differences between respondents with and without formal MFP training regarding provision of surgical treatments (P = 0.021) and dental oncology (P = 0.017). Most treatments were done together with otolaryngology, oral surgery (68%) and head and neck surgery (61%). Practitioners not affiliated with a university spent significantly more time in clinical practice (P = 0.002), whereas respondents affiliated with universities spent significantly more time in teaching/training (P = 0.008) and funded research (P = 0.015).
Personal satisfaction is the most important factor in a decision to choose an MFP career. Most of the MFPs work at a university and within a multidisciplinary setting. There were differences regarding type of treatments provided by respondents with and without formal MFP training.
Rehabilitation using an implant supported overdenture with two implants inserted in the interforaminal region is the easiest and currently accepted treatment modality to increase prosthetic stabilization and patient satisfaction in edentulous patients. The insertion of implants to the weakend mandibular bone decreases the strength of the bone and may lead to fractures either during or after implant placement. The aim of this three dimensional finite element analysis (3D FEA) study was to evaluate the biomechanical effects of implant diameter in case of facial trauma (2000 N) to an edentulous atrophic mandible with two implant supported overdenture.
Three 3D FEA models were simulated; Model 1 (M1) is edentulous atrophic mandible, Model 2 (M2), 3.5x11.5 mm implants were inserted into lateral incisors area of same edentulous atrophic mandible, Model 3 (M3), 4.3x11.5 mm implants were inserted into lateral incisors area of same edentulous atrophic mandible.
In M1 and M2 highest stress levels were observed in condylar neck, whereas highest stress values in M3 were calculated in symphyseal area.
To reduce the risk of bone fracture and to preserve biomechanical behavior of the atrophic mandible from frontal traumatic loads, implants should be inserted monocortically into spongious bone of lateral incisors area.
A link between progressive dental malocclusion, the use of a continuous positive airway pressure mask and GH-secreting pituitary macroadenoma (acromegaly) has not been previously reported. The present clinicopathological analysis stresses that tooth malposition should not be seen exclusively as a local process.
A 62-year-old caucasian man with no relevant medical history reported difficulty chewing food and perceived voice alteration during his annual periodontal check-up. He also referred stiffness of the tongue, face, and submandibular area. The patient had been diagnosed with obstructive sleep apnea syndrome two years previously, since when he had worn a continuous positive airway pressure device during sleep. Exploration of the occlusion revealed significant changes: an atypical left lateral and anterior open bite with major buccoversion of teeth 33, 34, 35, 36. Inspection of the soft tissue revealed only macroglossia, although external palpation indicated a subcutaneous stiffness of the submandibular area. General analytical tests, including hormone profiles, and magnetic resonance imaging confirmed the diagnosis of acromegaly induced by a pituitary adenoma. Intrasellar tumor resection via transsphenoidal approach was performed. After surgery, the patient already noted a marked improvement of all symptoms associated with the acromegaly. Desaturation data also evolved favourably and the pulmonologist advised the patient to abandon the continuous positive airway pressure treatment.
Progressive dental malocclusion may be associated with a systemic disease and the use of a nasal mask with premaxillary support may distort the diagnosis of acromegaly.
Parotidectomy is one of the most commonly performed procedures by otorhinolaryngologists. Traditionally dissection is performed with a combination of a steel scalpel and bipolar cautery; however, starting in the early 2000s, the Harmonic scalpel has provided an alternative method for dissection and hemostasis. The purpose of this study is to compare operative time, blood loss, complications, and cost between the Harmonic scalpel and steel scalpel plus bipolar cautery for superficial and total parotidectomy.
Retrospective cohort of patients who underwent superficial or total parotidectomy with the Harmonic or cold steel between 2000 and 2015. Across 255 patients, comparison between operative time, blood loss, complications, and cost was performed.
Superficial parotidectomy was performed on 120 patients with the Harmonic and 54 with steel scalpel. Total parotidectomy was performed on 59 patients using the Harmonic and 22 patients with cold steel. For superficial parotidectomy, the Harmonic reduced operative time (216 ± 42 vs. 234 ± 54 min, p = 0.03) and decreased blood loss (28 ± 19 vs. 76 ± 52 mls, p < 0.05). With total parotidectomy the Harmonic decreased operative time (240 ± 42 vs. 288 ± 78 min, p = 0.01) and reduced blood loss (38 ± 21 mls vs. 85 ± 55 mls, p < 0.05). There were no differences in complication rates between groups. Harmonic use was associated with surgical cost reduction secondary to reduced operative times.
The Harmonic scalpel decreases blood loss and operating time for superficial and total parotidectomy. Shorter operative times may decrease the overall cost of parotidectomy.
Eosinophilic chronic frontal sinusitis is difficult to treat compared with non-eosinophilic sinusitis because of recurring inflammation and polyp formation in the frontal recess after the post-operative follow-up period. Studying inflammatory mediators in the frontal recess of eosinophilic chronic rhinosinusitis (ECRS) patients and non-eosinophilic chronic rhinosinusitis (non-ECRS) patients may lead to a better understanding of the pathogenesis of chronic frontal sinusitis.
Homogenates of sinonasal mucosa from 20 non-ECRS patients and 36 ECRS patients were measured for levels of transforming growth factor (TGF)-β, interleukin (IL)-5, IL-6, and inducible nitric oxide synthase (iNOS) using real-time RT-PCR and TaqMan gene expression assays. Sinonasal mucosal specimens were obtained from the frontal recess, ethmoid sinus, and nasal polyp separately.
The expression of IL-5 was significantly elevated in all sinonasal regions tested in the ECRS group, but absent in non-ECRS patients. Furthermore, the ECRS patients showed significantly increased levels of IL-5 in the frontal recess mucosa compared with ethmoid sinus mucosa. IL-6 was also significantly increased in the frontal recess mucosa compared with ethmoid sinus mucosa and nasal polyps in these patients. There were no significant differences in the levels of TGF-β or iNOS between the ECRS and non-ECRS groups in any sinonasal region tested.
This study is the first to characterize the cytokine milieu in the frontal recess of ECRS patients. We should keep these cytokine profiles in mind when we treat ECRS patients with frontal sinusitis.
The National Institute for Health and Clinical Excellence (NICE) provides recommendations on health related quality of life (HRQoL) data used in submissions in their Guide to the Methods of Technology Appraisal. As different measures can produce different health state utility values (HSUV), the Institute state a preference for EQ-5D data to facilitate comparison across disease areas and interventions. However, inconsistencies in the methodologies used when applying HSUVs in economic models will produce discrepancies in results generated from decision analytic models, even when using the same measure, thus undermining policy decision making based on cost per quality adjusted life year (QALY) thresholds.
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This interim process statement has been produced to guide the development of good practice guidance. It provides an overview of the key process principles and describes all stages of the development of good practice guidance. These procedures are designed to ensure that a robust, quality-assured, resource is developed for the NHS in an open, transparent and timely way, with appropriate input from key groups.
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The NICE Guide to the Methods of Technology Appraisals recommends that quality adjusted life years (QALYs) are used as the measure of outcome for economic evaluation, and that the EQ-5D is the preferred measure of health-related utility to calculate QALYs. The guide also recognises that EQ-5D data may not always be available to analysts producing submissions and reports for NICE. Where such data are not available, the guide states that mapping can be used to predict EQ-5D data.
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The aim of this review was to inform the update of the NICE Technology Appraisal software requirements for economic model submissions.
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Publication date: Available online 28 April 2017
Source:Alexandria Journal of Medicine
Author(s): Mona Hajikazemi, Hoda Sohrabi, Ahad Yamchi, Mohsen Saeedi
Aim and objectivesThe histone deacetylase (HDAC) inhibitor, Valproic Acid (VPA), causes growth inhibition and apoptosis in colorectal cancer cells. HDAC inhibition is associated with the transcriptional regulation of Natriuretic Peptide Receptor-A (NPR-A). NPR-A regulates voltage-gated potassium channel, KQT-like subfamily Q, member 1 (KCNQ1). NPR-A and KCNQ1 are also involved in the initiation and propagation of cancer cells. In this study, we investigated the simultaneous expressional changes of NPR-A and KCNQ1 among VPA-treated colon cancer cells.Materials and methodsHuman colorectal cancer cells were cultured and treated with increasing concentrations of VPA at different time points. MTT viability test was conducted to evaluate the growth inhibition. Real Time RT-PCR was used to quantify differential mRNA expression of NPR-A and KCNQ1 genes. Two-way ANOVA and bonferroni post-tests were used to analyze data statistically.ResultsWe showed that VPA treatment inhibits the growth of SW-480 cells more efficiently compared to HT-29. NPR-A and KCNQ1 genes were significantly upregulated upon VPA treatment in both cell lines (P<0.0001).ConclusionThe alteration of NPR-A and KCNQ1 genes were more ordered among SW-480 cancer cells. The expressional changes of KCNQ1 and NPR-A among VPA treated human colon cancer cells follow the same pattern in similar combinations. VPA could regulate the expression of KCNQ1 through altering the mRNA expression of NPR-A.
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Publication date: Available online 26 April 2017
Source:Alexandria Journal of Medicine
Author(s): Abdullahi Hassan, Gobir Abdulrazaq Abdullahi, Abubakar Aisha Ahmed, Adamu Sabiu, Uwaya John, Gwamna Ezekeil, Yahaya Aliyu Ibrahim
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The NICE Guide to the Methods of Technology Appraisal expresses a preference for using the EQ-5D for adult populations to estimate the Quality Adjusted Life Year (QALY) impact of different technologies. Alternative methods to generating health state utility values (HSUVs) will be considered by NICE in place of EQ-5D when EQ-5D data are either unavailable or inappropriate. Unavailability should be established from a systematic search of the literature. Even if EQ-5D data is unavailable, mapping can be used as an alternative to estimate EQ-5D values rather than the alternative methods described in this Technical Support Guide (see TSD 101). Claims that EQ-5D is inappropriate for measuring the Health Related Quality of Life (HRQL) for a patient group or a specific treatment must be supported by evidence.
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Publication date: Available online 8 May 2017
Source:Alexandria Journal of Medicine
Author(s): Heba Mahmoud Taha Elweshahi, Gihan Ismail Gewaifel, Sameh Saad EL-Din Sadek, Omnia Galal El-Sharkawy
BackgroundPostpartum women are a priority group to target on trying to solve the problem of closely spaced pregnancies as well as population explosion.AimTo estimate the level of unmet need for postpartum family planning one year after birth as well as identify factors associated with having unmet need in Alexandria, Egypt.MethodsA cross sectional survey was adopted. A sample of 1500 women one year post-partum was selected. A predesigned interviewing questionnaire was used to collect data. Data include their socio-demographic characteristics and current use of family planning method. Those with unmet need for postpartum family planning (PPFP) were asked about the reasons for non-use, their intention to use in the future and their knowledge about contraceptives.SettingPublic settings delivering routine immunization for infants in Alexandria.ResultsOut of 1500 postpartum women, 1370 (91.33%) have a real demand for family planning. Out of those with a real demand for family planning (n=1370), 1106 (80.72%) were using a modern contraceptive method and only 41 (3%) were using a traditional method for birth control while the remaining 223 (16.28%) were having unmet need for postpartum family planning. Amenorrhea, breast feeding, fear of side effects, discontinuation due to health concerns and pressure from the surroundings were the most common cited reasons for non-use.ConclusionIntegration of family planning education during antenatal, natal and postnatal care services in Egypt should be actively initiated. Women with unmet need for PPFP in general and those with intention to use a contraceptive in particular should be targeted for recruitment efforts and services in any program tackle the problem of family planning and rising fertility in Egypt.
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Publication date: Available online 5 May 2017
Source:Alexandria Journal of Medicine
Author(s): Sima Chauhan, Sarita Pradhan, Ripunjaya Mohanty, Abhishek Saini, Kumudini Devi, Mahesh Chandra Sahu
IntroductionBone marrow aspiration (BMA) and bone marrow biopsy (BMB) is an indispensable diagnostic tool for evaluating haematological and non-haematological disorders and patient follow-up in present era. We have compared the advantages of trephine biopsy over bone marrow aspiration in these patients.Aim and objectiveTo evaluate sensitivity and specificity of trephine biopsy test for haematological and non haematological disorder patients in comparison to bone marrow aspiration test.Materials and methodIn this 1year prospective study (June 2014–May 2015), we evaluated the haematological and non-haematological disorder patients by BMA and BMB (aided with I.H.C. when ever needed). The sensitivity and specificity of the tests were calculated.ResultsAmong, final 504 hemotological/non haematological disorder patients, 416 cases were diagnosed (+ve) in BMA test, where as it was 494 in BMB test and with chi2 test it was highly significant as p=0.0001. It was concluded that True positive cases were 416, True negative were 9 cases, false negative 78 cases and false positive was in one case only. The sensitivity and specificity of bone marrow trephine biopsy test was 84% and 90% respectively.ConclusionBMB (aided with I.H.C) is a gold standard test for detecting different haematological and non hamatological disorders. In our study the sensitivity and specificity of BMB test was 84% and 90% respectively. When performed in association with BMA in the same sitting, significantly augments the chances of reaching a correct diagnosis.
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The National Institute for Health and Care Excellence (NICE) is the independent body responsible for driving improvement and excellence in the health and social care system. We develop guidance, standards and information on high-quality health and social care. We also advise on ways to promote healthy living and prevent ill health.
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The aim of this review is to provide an overview of how innovation is currently valued in the UK health system and the potential initiatives that can be adopted in order to promote innovation in the NHS. The report includes a review of the scientific, policy and economic literature.
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This interim process statement has been produced by the National Institute for Health and Clinical Excellence (NICE) to guide the development of the QIPP key therapeutics document, 'Key therapeutic topics – Medicines management options for local implementation'. It provides an overview of the key process and principles, and describes all stages of the development of the QIPP key therapeutics document. These procedures are designed to ensure that a robust, quality-assured document is developed for the NHS in an open, transparent and timely way, with appropriate input from key groups. This interim process statement uses the NICE Implementation Support Tool process as an overarching guide to the principles of its development.
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This project developed as a result of the activities of the Research Teams at the Centre for Health Economics, University of York, and ScHARR at the University of Sheffield in the methods and application of decision analysis and value of information analysis as a means of informing the research recommendations made by NICE, as part of its Guidance to the NHS in England and Wales, and informing the deliberations of the NICE Research and Development Committee.
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This Technical Support Document (TSD) is concerned with methods for identifying and reviewing evidence to inform models developed to estimate the cost-effectiveness of health technologies, in particular model parameter estimates, in the NICE Technology Appraisal Process. The NICE Guide to the Methods of Appraisal states that for parameters relating to treatment effects a full systematic review is required, and that the process of assembling evidence for all parameters needs to be systematic, transparent and justifiable. Evidence must be identified, quality assessed and, when appropriate, pooled using explicit criteria and justifiable and reproducible methods. The Methods Guide goes on to state that evidence will typically be drawn from a number of different sources. These sources might include cohort studies for parameters relating to the natural history of the condition, randomised controlled trials for relative treatment effects, and cross-sectional surveys for resource use and costs. Methodological standards for reviewing the broad range of relevant evidence in the context of model development do not currently exist. The processes through which evidence is identified and selected remain largely unreported with the result that the process of using evidence within models lacks transparency. Guidance is needed regarding approaches for reviewing of evidence to inform the model development process and for informing parameter values in cost-effectiveness models.
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NICE guidance on health technologies includes the use of new and existing medicines, treatments and procedures in the NHS; this includes medicines and use of medical devices and diagnostics. Putting NICE guidance into practice can be challenging, and this is why NICE provides support.
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Health state utility values (HSUVs) are important parameters in decision models, and NICE requires evidence that HSUV estimates from the published literature have been identified and selected systematically. NICE provides a reference case analysis with specific requirements for how HSUVs are derived, including a preference for HSUV values derived from the EQ-5D. This Technical Support Document (TSD) discusses how to systematically identify and select HSUVs from the literature in order to meet the requirements of the NICE Methods Guide. In addition, the TSD provides guidance on quality and relevance assessment, data extraction, selection of values and synthesis. Two case studies are used throughout this document; a review of HSUVs in osteoporosis-related conditions and a review of HSUVs in breast cancer.
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This interim process statement has been produced to guide the development of 'Evidence summaries: new medicines' (ESNMs). It provides an overview of the key process principles and describes all stages of the development of ESNMs. These procedures are designed to ensure that a robust, quality-assured, commentary is developed for the NHS in an open, transparent and timely way, with appropriate input from key groups.
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This interim process statement has been produced to guide the development of 'Evidence summaries: unlicensed and off-label medicines' (ESUOMs). It provides an overview of the key process principles and describes all stages of development for ESUOMs. These procedures are designed to ensure that a robust, quality-assured, commentary is developed for the NHS in an open, transparent and timely way, with appropriate input from key groups.
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NICE requires consistency in its decision making and so has developed a reference case of methods for Technology Appraisal that includes the measurement and valuation of health.
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This integrated process statement relates to the document 'Medicines optimisation: key therapeutic topics' (hereafter referred to as key therapeutic topics). It has been produced to explain how key therapeutic topics are developed. It provides an overview of the key process and principles, and describes all stages of the development of key therapeutic topics. These procedures are designed to ensure that a robust, quality-assured document is developed in an open, transparent and timely way, with appropriate input from key groups. This process statement uses the NICE Implementation Support Tool process as an overarching guide to the principles of its development.
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Determination of biomarkers may be useful in the surveillance of occupational exposure and workers' health. The possibility of predicting development/clinical course of specific disorders or current disease, diagnosing in early steps, and health condition monitoring is a real necessity. Various agents present in the workplace environment (or their metabolites) can be measured in samples possessed from human body (blood and urine, saliva, etc.). On the other hand, inhalant exposure may induce specific or non-specific, local or systemic, acute or chronic biological response expressed by synthesis or releasing specific or non-specific substances/mediators that also can be determined in blood, nasal and bronchial lavage or sputum, tear fluid, exhaled breath, etc. The least is known about genetic markers which may predict individual susceptibility to develop some work-related disorders under the influence of occupational exposure. Due to common exposure to inhalant agents at workplace, researches on biomarkers that allow to inspect the impact of exposure to humans' health are still needed. The authors of this article summarize the utility of biomarkers' determination in work-related airway diseases in a recent clinical approach.
Subcutaneous allergen immunotherapy (SCIT) is a well-documented treatment for allergic disease which involves injections of native allergen or modified (allergoid) extracts. The use of allergoid vaccines is a ...
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Publication date: 15 June 2017
Source:International Journal of Pharmaceutics, Volume 525, Issue 1
Author(s): Zimeng Wang, Sweta K. Gupta, Samantha A. Meenach
Biocompatible, biodegradable polymers are commonly used as excipients to improve the drug delivery properties of aerosol formulations, in which acetalated dextran (Ac-Dex) exhibits promising potential as a polymer in various therapeutic applications. Despite this promise, there is no comprehensive study on the use of Ac-Dex as an excipient for dry powder aerosol formulations. In this study, we developed and characterized pulmonary drug delivery aerosol microparticle systems based on spray-dried Ac-Dex with capabilities of (1) delivering therapeutics to the deep lung, (2) targeting the particles to a desired location within the lungs, and (3) releasing the therapeutics in a controlled fashion. Two types of Ac-Dex, with either rapid or slow degradation rates, were synthesized. Nanocomposite microparticle (nCmP) and microparticle (MP) systems were successfully formulated using both kinds of Ac-Dex as excipients and curcumin as a model drug. The resulting MP were collapsed spheres approximately 1μm in diameter, while the nCmP were similar in size with wrinkled surfaces, and these systems dissociated into 200nm nanoparticles upon reconstitution in water. The drug release rates of the Ac-Dex particles were tuned by modifying the particle size and ratio of fast to slow degrading Ac-Dex. The pH of the environment was also a significant factor that influenced the drug release rate. All nCmP and MP systems exhibited desirable aerodynamic diameters that are suitable for deep lung delivery (e.g. below 5μm). Overall, the engineered Ac-Dex aerosol particle systems have the potential to provide targeted and effective delivery of therapeutics into the deep lung.
Inhalation of food-derived allergens during food processing at the workplace represents a risk for developing occupational asthma (OA) in exposed workers. Cereal flours and seafood are the causal agents most frequently involved. The management of food-derived OA includes timely pharmacologic therapy and environmental interventions aimed to avoid or reduce exposure to the offending agent to increase the probability of recovery. Cessation of exposure is the best option, but when the causative agent cannot be completely avoided reduction of exposure, through modification of food processing, improving ventilation, mechanization, etc. can be considered as an alternative. Quantification of real exposure levels is crucial, and new accurate immunologic and chemical assays able to detect low levels of aerosolized flour and seafood allergens have recently been developed. Recent papers have described intervention strategies effective in reducing airborne allergen exposure in flour and seafood industry, but the long-term health impact of this intervention has still to be defined. Specific allergen immunotherapy (SIT) might be another management option in individuals with IgE-mediated food-induced OA. Both a short- and a long-lasting beneficial effect of SIT with wheat flour in reducing symptoms whilst keeping the patient at work has been shown in bakers' asthma, but at present, SIT is not for routine use for bakers' asthma due to the lack of commercial standardized extracts. A better identification on a molecular basis of allergens involved in flour and in other IgE-mediated food-derived OA might help in preparing new extracts suitable for immunotherapy. In selected cases of bakers' asthma, the monoclonal antibody omalizumab has been effective in reducing symptoms. SIT and omalizumab might represent further management options in IgE-mediated OA in food industry.
Data on adverse drug reactions (ADRs) is abundant, especially regarding prevalence and incidence among hospital-based populations. Most studies, however, do not differentiate between drug hypersensitivity reactions (DHRs) and other kinds of ADR, and in those ones where this information is available, the diagnosis of DHR or drug allergy is mostly based on a suspected clinical history or self-reporting as the majority of patients are not referred for an allergy diagnostic workup. Large studies in drug allergy clinics revealed that only 10 to 20% of the initial DHR suspicions are actually confirmed after investigation. Diagnosis based only on clinical histories largely overestimates drug hypersensitivity, so specific data on DHR is scarce and generally of low quality. Epidemiological data, although limited, can help researchers to identify potential risk factors for DHR. Females seem to be more susceptible than males to ADR and DHRs in adult populations, while the female gender is not a risk factor among children. ADRs have also a higher incidence among young children and among the elderly. The role of atopy as a risk factor for DHR is still debatable; however, recent evidence shows that it can actually be important considering reactions to betalactams and NSAIDs. Comorbidities as infections and underlying chronic diseases are known risk factors both for ADR in general and for DHR. The most recent investigation concentrates on the importance of genetic risk factors, and many gene polymorphisms have been identified with strong associations to particular kind of DHR and/or to reactions to specific drugs. This article will discuss general limitations of the available epidemiological data on DHR and will present an in-depth review of the main identified risk factors for drug reactions with special focus on genetic findings.
Poor asthma control observed in several surveys may be related to a lack of systematic assessment by physicians and/or to patient underestimation of symptoms. Along this line, the purpose of this study was to ...
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Currently, young asthmatics have little knowledge of the potential effects of work exposures on their asthma. We expect that education of young asthmatics about the potential effects of the working environment on their asthma and appropriate steps to reduce work-related exacerbations will provide these individuals with skills to better control their asthma. Currently, there is no formal process for this education to our knowledge. Since the Internet is readily available and widely used by most young asthmatics, it may provide a useful forum for such education. Our preliminary studies with development and early validation of a Web-based educational tool for work-related asthma suggest that this can provide education and may prove to be a useful resource. Additional studies are needed to determine whether this can be easily used in high schools or trade schools or in the workplace, and whether the knowledge gained can translate into reduction of morbidity. Potentially, benefit may also accrue to older working adults with asthma or those at increased risk of developing occupational asthma.
Enhancing the repertoire of in vitro methods together with the development of recombinant technology in the field of allergy diagnosis brought tremendous advances in understanding allergens, allergic reactions, and patients' care. This review is focusing not only on component-resolved diagnosis with occupational allergens, complementary methods, their advantages to improve the in vitro diagnosis for occupational allergy but also their limitations. Up to now, the number of occupational asthma sensitizers characterized on the molecular level and their availability for routine diagnosis is very low. One exception, however, is Hevea brasiliensis latex as an important occupational allergen source. H. brasiliensis latex is an excellent model for the useful application of recombinant single allergens for improvement of routine diagnostics. Despite the many efforts and excellent research in the field of baker's asthma to characterize the occupationally relevant allergens the results are highly diverse. No major allergen can be identified and the IgE-sensitization profile of each baker showed great inter-individual variation. Therefore, for routine diagnosis of baker's asthma, the assessment of allergen-specific IgE with the whole wheat (and/or rye) flour extract is still recommended. Unfortunately, no wheat allergens relevant for baker's asthma are commercially available, although they might help to discriminate between wheat-induced food allergy, grass pollen allergy, and baker's asthma. In particular cases with discrepancy between different diagnostic tests, the determination of basophil activation test is a recommended option. Flow cytometry determination of CD63 or CD203c on basophils induced by stimulation with the relevant allergen is a good clinically validated test and also useful for the diagnosis of occupational allergy. It is still necessary to increase the knowledge of occupational allergen molecules and include standardized tools into routine diagnostic. For the future, combination of new diagnostic tools and biomarkers, platforms, and complementary methods in occupational allergy and asthma diagnosis is a promising option. In addition, integration of these possibilities in workplace-related allergy and asthma studies is helpful to understand the complex interaction between work-related exposure, individual susceptibility and health outcome.
Allergic and hypersensitivity reactions such as anaphylaxis and asthma exacerbations may occur during air travel. Although the exact incidence of in-flight asthma and allergic emergencies is not known, we have...
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Occupational asthma is a type of asthma that arises from exposures in the workplace. There are more than 400 known causes of occupational asthma and the list is growing. New causes of allergic occupational asthma involving high and low molecular weight agents are continuously being reported. Their knowledge is important for physicians and occupational health and safety professionals to maintain a high level of suspicion in exposed workers to these substances. The majority of new causes of allergic occupational asthma between 2011 and mid-2016 were seen with high-molecular-weight agents. Most new cases are observed in food and agro-alimentary industry, but also in the cosmetic industry, and frequently are associated with other IgE-mediated manifestations, especially allergic rhinoconjunctivitis and contact urticaria. Among the low-molecular weight agents, new acrylate and aldehyde compounds have been identified as eliciting agents of occupational asthma, as well as drugs, biocides, and other chemicals recently introduced in industry.
Since mite allergens are the most relevant inducers of allergic diseases worldwide, resulting in significant morbidity and increased burden on health services, the International Collaboration in Asthma, Allerg...
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Publication date: 2017
Source:Conn's Current Therapy 2017
Author(s): Edward T. Bope, Rick D. Kellerman
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A previous survey on the practice of diagnostic patch testing among representatives of member societies of the World Allergy Organization (WAO) has, in some countries, not addressed those stakeholders actually...
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Publication date: 2017
Source:Examination Medicine
Author(s): Nicholas J Talley, Simon O'Connor
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Publication date: Available online 3 May 2017
Source:Journal of Proteomics
Author(s): Martina Grochalová, Hana Konečná, Karel Stejskal, David Potěšil, Danuše Fridrichová, Eva Srbová, Kateřina Ornerová, Zbyněk Zdráhal
We adopted an approach based on peptide immobilized pH gradient-isoelectric focusing (IPG-IEF) separation, coupled with LC-MS/MS, in order to maximize coverage of the beer proteome. A lager beer brewed using traditional Czech technology was degassed, desalted and digested. Tryptic peptides were separated by isoelectric focusing on an immobilized pH gradient strip and, after separation, the gel strip was divided into seven equally sized parts. Peptides extracted from gel fractions were analyzed by LC-MS/MS. This approach resulted in a three-fold increase in the number of proteins identified (over 1700) when compared to analysis of unfractionated beer processed by a filter-aided sample preparation (FASP). Over 1900 protein groups (PGs) in total were identified by both approaches.SignificanceThe study significantly extends knowledge about the beer proteome and demonstrates its complexity. Detailed knowledge of the protein content, especially gluten proteins, will enhance the evaluation of potential health risks related to beer consumption (coeliac disease) and will contribute to improving beer quality.
The term "united airway disease" has been used since 2000 to describe the strong association between asthma and rhinitis. Although this term is not extensively used, it refers to the fact that asthma and rhinitis are frequently associated and share common risk factors, causal agents and mechanisms. Similarly, since 2010 the term occupational united airway disease has been used to describe the strong association between occupational asthma and rhinitis. Rhinitis and occupational rhinitis are less severe diseases but more frequent than asthma and occupational asthma, respectively. Every year several case reports and epidemiological studies enhance the long list of agents responsible for occupational asthma and rhinitis with new agents or occupations. Primary, secondary and tertiary prevention strategies are aimed at reduction of the onset and severity of work-related respiratory diseases. Primary prevention mainly includes avoiding/reducing exposure to known sensitizing/irritant agents. Secondary prevention or early detection should focus on medical surveillance of individuals at risk, health and safety education and training of workers, and recognition of early bronchial/nasal symptoms. Tertiary prevention includes early recognition and diagnosis, appropriate removal from further exposure and pharmacologic treatment. Unfortunately, pharmacologic treatment has seldom been studied in occupational asthma and rhinitis, and it usually refers to the international guidelines of management of asthma and rhinitis aimed to achieve control of the two diseases. For simultaneous treatment of asthma and rhinitis, the anti-IgE monoclonal antibody omalizumab, effective in occupational asthma and rhinitis, is available. Immunotherapy has been shown to be effective in health care workers with occupational asthma due to natural rubber latex, in workers with occupational asthma due to laboratory animals and in baker's asthma. A limitation of immunotherapy, however, can be systemic reactions after subcutaneous injections of sometimes non-standardized and non-purified extracts.
FeNO is a simple non-invasive tool used as a surrogate marker of airway inflammation in the management of asthma. FeNO has been assessed in several populations of workers exposed to high- and low-molecular weight agents. However, there are many confounding factors to consider in the interpretation of FeNO. As such, its use in the investigation of occupational asthma (OA) has yielded inconsistent results. In screening studies of OA to high molecular weight (HMW) agents, an increase of FeNO over time has been associated with the development of bronchial hyperresponsiveness (BHR). When used in the investigation of OA, increases in FeNO show high positive predictive values for a positive specific inhalation challenge (SIC) to HMW agents. Subjects with high specific IgE to their workplace allergens seem to present higher increases in FeNO than subjects without specific IgE to causal agent. Changes in FeNO have less frequently been observed in studies of OA to low molecular weight (LMW) agents than OA to HMW agents, except for isocyanate-induced OA. Cluster analyses of patients exposed to various HMW and LMW agents have documented significant increases of FeNO in clusters of patients with OA to HMW agents, but not LMW. Recent studies have provided useful information for improving our understanding of the pathophysiology of exhaled NO in OA despite the previously reported conflicting results. Future studies are still required to clarify its role in the screening, investigation, and management of OA.
Non-steroidal anti-inflammatory drugs (NSAIDs)-exacerbated respiratory disease (NERD) is defined by the combination of chronic rhinosinusitis, nasal polyps, bronchial asthma, and hypersensitivity reactions involving upper and/or lower airways after the exposure to acetylsalicylic acid (ASA) and other NSAIDs. However, airway inflammation occurs even in the absence of exposure to these drugs, leading to disease progression with aggressive polyp formation and non-optimal controlled asthma and rhinosinusitis. In this review, we discuss current and potential management strategies of NERD. This management should be multidisciplinary and comprise medical and surgical treatment of the underlying diseases. In order to prevent reactions due to NSAIDs, avoidance of COX-1 inhibitors with provision of safe therapeutic alternatives should be indicated. However, avoidance of NSAIDs does not ensure disappearance of the airway inflammation and this progresses and persists for life. ASA desensitization followed by daily ASA therapy remains the gold standard of NERD treatment. It is indicated in patients with uncontrolled bronchial and nasal symptoms as well as in patients who require NSAID treatment for specific diseases, such as rheumatic or cardiovascular conditions. ASA desensitization improves upper and lower respiratory symptoms, reduces the need for new nasal surgeries and increases quality of life. Different ASA desensitization protocols have been reported, although the addition of intranasal ketorolac and lysine aspirin prior to an oral ASA schedule has made ASA desensitization safer and more efficient. New therapeutic strategies are being investigated and may provide an alternative treatment for those patients in which ASA desensitization are contraindicated or continuous ASA therapy is discontinued because of adverse effects. Among them, biologic agents are an important treatment option, useful for controlling symptoms of the upper and lower airways. More investigation studies into the mechanisms involved in NERD are needed in order to identify additional therapeutic targets.
Occupational asthma is an important social, health, and economic burden in our society, but its treatment options have not been yet sufficiently explored. Drug therapies do not differ much from ordinary asthma treatments, and avoidance is the main managing option for this condition. However, other therapeutic options like immunotherapy and biological therapies have not been used as in other asthma and rhinitis etiologies. Occupational asthma has different pathomechanisms depending of its triggers, but in immunological IgE-dependent asthma, these therapies can be fairly efficient. Not many immunotherapy studies have been carried out lately on this topic, and its reproducibility might be its biggest disadvantage. Maybe the main existing limitation is the lack of standardized extracts in order to perform this treatment. With no proper extracts, this treatment cannot be implemented, and its tolerance is going to differ depending on the extract used in each specific case. On the other hand, biological treatments are a promising option in the management of severe occupational asthma. Not many studies have been conducted so far in occupational allergy. Nevertheless, these biological treatments are upcoming and evolving therapies, so we expect further studies in a close future, including recently approved therapeutic options such as mepolizumab in eosinophilic refractory asthma. These new treatment possibilities should enhance their use and empower them also in the occupational field.
The aim of this study is to focus the spotlight in these asthma treatments to encourage the study of its efficacy in occupational asthma, try to optimize the treatment options for this disorder, and bring these infrequent treatments out of the ostracism where they are found nowadays.
Parotidectomy is one of the most commonly performed procedures by otorhinolaryngologists. Traditionally dissection is performed with a combination of a steel scalpel and bipolar cautery; however, starting in the early 2000s, the Harmonic scalpel has provided an alternative method for dissection and hemostasis. The purpose of this study is to compare operative time, blood loss, complications, and cost between the Harmonic scalpel and steel scalpel plus bipolar cautery for superficial and total parotidectomy.
Retrospective cohort of patients who underwent superficial or total parotidectomy with the Harmonic or cold steel between 2000 and 2015. Across 255 patients, comparison between operative time, blood loss, complications, and cost was performed.
Superficial parotidectomy was performed on 120 patients with the Harmonic and 54 with steel scalpel. Total parotidectomy was performed on 59 patients using the Harmonic and 22 patients with cold steel. For superficial parotidectomy, the Harmonic reduced operative time (216 ± 42 vs. 234 ± 54 min, p = 0.03) and decreased blood loss (28 ± 19 vs. 76 ± 52 mls, p < 0.05). With total parotidectomy the Harmonic decreased operative time (240 ± 42 vs. 288 ± 78 min, p = 0.01) and reduced blood loss (38 ± 21 mls vs. 85 ± 55 mls, p < 0.05). There were no differences in complication rates between groups. Harmonic use was associated with surgical cost reduction secondary to reduced operative times.
The Harmonic scalpel decreases blood loss and operating time for superficial and total parotidectomy. Shorter operative times may decrease the overall cost of parotidectomy.
A link between progressive dental malocclusion, the use of a continuous positive airway pressure mask and GH-secreting pituitary macroadenoma (acromegaly) has not been previously reported. The present clinicopathological analysis stresses that tooth malposition should not be seen exclusively as a local process.
A 62-year-old caucasian man with no relevant medical history reported difficulty chewing food and perceived voice alteration during his annual periodontal check-up. He also referred stiffness of the tongue, face, and submandibular area. The patient had been diagnosed with obstructive sleep apnea syndrome two years previously, since when he had worn a continuous positive airway pressure device during sleep. Exploration of the occlusion revealed significant changes: an atypical left lateral and anterior open bite with major buccoversion of teeth 33, 34, 35, 36. Inspection of the soft tissue revealed only macroglossia, although external palpation indicated a subcutaneous stiffness of the submandibular area. General analytical tests, including hormone profiles, and magnetic resonance imaging confirmed the diagnosis of acromegaly induced by a pituitary adenoma. Intrasellar tumor resection via transsphenoidal approach was performed. After surgery, the patient already noted a marked improvement of all symptoms associated with the acromegaly. Desaturation data also evolved favourably and the pulmonologist advised the patient to abandon the continuous positive airway pressure treatment.
Progressive dental malocclusion may be associated with a systemic disease and the use of a nasal mask with premaxillary support may distort the diagnosis of acromegaly.
Squamous cell carcinomas (SCCs) are the most prevalent malignant tumours within the head and neck. Evidence exists that distinct genes are differentially regulated in SCCs of the oral cavity compared to other head and neck regions. Given this background, the aim of this study was to investigate whether such tumour site-specific gene expression can also be observed in different localizations within the oral cavity.
Using tissue microarrays (TMAs), we investigated 76 SCCs of the floor of the mouth, 49 SCCs of the tongue and 68 SCCs of other anatomic regions within the oral cavity. The expression of 17 genes involved in cell cycle and growth control (p16, p21, p27, p53, cyclin D1, EGFR, c-kit, bcl-6), cell adhesion (alpha-, beta-, and gamma-catenin), and apoptosis/stress response genes (Hif-1-alpha, Glut 1, CA IX, caspase, hsp70, XIAP) were investigated by means of immunohistochemistry. The data were subjected to chi2, interdependency and Kaplan-Meier analysis.
Our study suggests a remote difference in the site-specific gene expression patterns of oral cancer. X-linked inhibitor of apoptosis (XIAP) showed a significantly higher expression (p <0.05) in SCCs of the floor of the mouth compared to SCCs of the tongue and other locations within the oral cavity. The increased XIAP expression was further associated with significantly decreased overall survival in all cases of SCCs of the oral cavity (p <0.05). Expression levels of p53, CA IX, beta-catenin, Hif-1-alpha, and c-kit were also observed to be inversely related between SCCs of the floor of the mouth and those of the tongue respectively, although these differences did not reach statistical significance. Overall and event-free survival did not differ in patients with T1/T2/N0 SCCs according to tumour localization.
In summary, the protein expression patterns of SCCs of the oral cavity suggest the existence of a molecular and morphological spectrum of SCCs in the oral cavity. In particular the expression pattern of XIAP indicates distinct gene expression patterns between carcinomas of the floor of the mouth and oral tongue cancer. Further studies are needed to identify possible tumour site-specific factors that influence patient prognosis and management.
Rehabilitation using an implant supported overdenture with two implants inserted in the interforaminal region is the easiest and currently accepted treatment modality to increase prosthetic stabilization and patient satisfaction in edentulous patients. The insertion of implants to the weakend mandibular bone decreases the strength of the bone and may lead to fractures either during or after implant placement. The aim of this three dimensional finite element analysis (3D FEA) study was to evaluate the biomechanical effects of implant diameter in case of facial trauma (2000 N) to an edentulous atrophic mandible with two implant supported overdenture.
Three 3D FEA models were simulated; Model 1 (M1) is edentulous atrophic mandible, Model 2 (M2), 3.5x11.5 mm implants were inserted into lateral incisors area of same edentulous atrophic mandible, Model 3 (M3), 4.3x11.5 mm implants were inserted into lateral incisors area of same edentulous atrophic mandible.
In M1 and M2 highest stress levels were observed in condylar neck, whereas highest stress values in M3 were calculated in symphyseal area.
To reduce the risk of bone fracture and to preserve biomechanical behavior of the atrophic mandible from frontal traumatic loads, implants should be inserted monocortically into spongious bone of lateral incisors area.
Publication date: 2018
Source:Integrative Medicine
Author(s): Alan R. Gaby
http://ift.tt/2puhZPI
Publication date: 2017
Source:Examination Medicine
Author(s): Nicholas J Talley, Simon O'Connor
http://ift.tt/2r48Kb6
Publication date: Available online 3 May 2017
Source:Journal of Proteomics
Author(s): Martina Grochalová, Hana Konečná, Karel Stejskal, David Potěšil, Danuše Fridrichová, Eva Srbová, Kateřina Ornerová, Zbyněk Zdráhal
We adopted an approach based on peptide immobilized pH gradient-isoelectric focusing (IPG-IEF) separation, coupled with LC-MS/MS, in order to maximize coverage of the beer proteome. A lager beer brewed using traditional Czech technology was degassed, desalted and digested. Tryptic peptides were separated by isoelectric focusing on an immobilized pH gradient strip and, after separation, the gel strip was divided into seven equally sized parts. Peptides extracted from gel fractions were analyzed by LC-MS/MS. This approach resulted in a three-fold increase in the number of proteins identified (over 1700) when compared to analysis of unfractionated beer processed by a filter-aided sample preparation (FASP). Over 1900 protein groups (PGs) in total were identified by both approaches.SignificanceThe study significantly extends knowledge about the beer proteome and demonstrates its complexity. Detailed knowledge of the protein content, especially gluten proteins, will enhance the evaluation of potential health risks related to beer consumption (coeliac disease) and will contribute to improving beer quality.
Publication date: 2017
Source:Ferri's Clinical Advisor 2017
Author(s): Fred F. Ferri
http://ift.tt/2qub7He
Recent studies seem to indicate that apoptosis and autophagy can act cooperatively in fish ovaries in order to achieve more effective ovarian regression after spawning. Considering the importance of tissue remodeling in ovarian functioning, we sought to morphologically characterize the involution processes of follicular atresia and post-ovulatory complexes using Astyanax altiparanae as an experimental model, and to determine the location of proteins involved in apoptosis and autophagy throughout this process. Fifteen females were collected after reproductive management. Fragments of the left ovaries were removed, fixed, and prepared for light microscopy and immunofluorescence analyses. The main characteristics of the involution processes were found to be consistent with previous descriptions. However, there were certain morphological peculiarities that do not appear to have been described for any other species thus far. These peculiarities may be related to the focus of this study on a single species, which allows for a more detailed investigation into morphological changes than studies on multiple species. Autophagy was also found to precede apoptosis in both involution processes in A. altiparanae. This may be related to the energy recycling process required before the removal of degenerated follicular cells by apoptosis. Thus, these results support the idea that there is crosstalk between autophagy and apoptosis pathways in ovarian involution processes, as well as the idea that the cell death pathways of these processes are conserved between teleost species with external fertilization.
Publication date: 2017
Source:Pediatric Primary Care
Author(s): Martha Driessnack, Sandra Daack-Hirsch
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Publication date: 2017
Source:Ferri's Clinical Advisor 2017
Author(s): Fred F. Ferri
http://ift.tt/2r4agKw
Publication date: 2017
Source:Ferri's Clinical Advisor 2017
http://ift.tt/2r46DUz
Publication date: 2017
Source:Ferri's Clinical Advisor 2017
Author(s): Fred F. Ferri
http://ift.tt/2qualK7
Publication date: 2018
Source:Integrative Medicine
Author(s): Alan R. Gaby
http://ift.tt/2puhZPI
Publication date: 2016
Source:Andrews' Diseases of the Skin
http://ift.tt/2r4jbM3
Publication date: 2016
Source:Cardiovascular Intervention
Author(s): Nicolas W. Shammas
http://ift.tt/2qul5Ix
Power Doppler in combination with three-dimensional (3D-PD) ultrasonography has been used as a noninvasive tool to evaluate the vascularity. However, it is unclear whether 3D-PD can accurately reflect endometrial vascularization and replace the invasive endometrial biopsy. This study aims to investigate the correlation between 3D-PD and micro vessel morphometric measurement of endometrial vascularity. Twenty-five women with unexplained recurrent miscarriage were recruited for 3D-PD and endometrial biopsy on precisely day LH + 7. Immunohistochemistry using vWF was employed to identify micro vessels in endometrial biopsy specimens followed by the use of morphometric technique to measure the mean vessel diameter and volume fractions. The vascularization index (VI), flow index (FI) and vascularization flow index (VFI) assessed by 3D-PD were calculated for both the endometrial and sub-endometrial regions. There were no significant correlations between any of the ultrasonographic measurements (endometrial thickness, endometrial volume, endometrial VI/FI/VFI, sub-endometrial volume, sub-endometrial VI/FI/VFI) and morphometric features (number of micro vessel, mean diameter of micro vessel and volume fraction measurement of vessel). This study indicates that endometrial vascularity assessed by 3D-PD could not be used to reflect changes in micro vessels of the endometrium at the time of embryo implantation in women with unexplained recurrent miscarriage.
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Clinical Features of Patients with Basedow's Disease and High Serum IgG4 Levels.
Intern Med. 2017;56(9):1009-1013
Authors: Torimoto K, Okada Y, Kurozumi A, Narisawa M, Arao T, Tanaka Y
Abstract
Objective IgG4-related disease is a recently characterized condition presenting with high blood IgG4 levels, swelling of organs, and hypertrophic lesions. This disease is associated with thyroid disease, Hashimoto's disease, and Riedel's thyroiditis. However, there is little information on the association between IgG4-related disease and Basedow's disease. We herein defined the clinical features of patients with Basedow's disease and high IgG4 levels. Methods We compared two groups of patients with Basedow's disease (n=72) who had either normal IgG4 levels (<135 mg/dL; n=67) or high IgG4 levels (≥135 mg/dL; n=5 [6.9%], mean IgG4: 206±116 mg/dL, IgG4/IgG ratio: 10.6%±3.3%). Patients Seventy-two newly diagnosed, untreated patients with Basedow's disease. Results Compared to the normal IgG4 group, patients in the high IgG4 group were predominantly male and showed a significantly higher thyroid low-echo score (1.8±0.4 vs. 1.2±0.5) and eosinophil count (363±354/mm(2) vs. 136±122/mm(2)). Five patients had high IgG4 levels: one had a pancreatic lesion, and four had thyroid lesions. Conclusion Patients with Basedow's disease and high IgG4 levels may represent a new subtype of Basedow's disease. Further studies with larger sample sizes are needed.
PMID: 28458304 [PubMed - in process]
Publication date: 2018
Source:Zakim and Boyer's Hepatology
Author(s): Phillip Factor, Sammy Saab
http://ift.tt/2r4loab
Publication date: September 2017
Source:Advances in Medical Sciences, Volume 62, Issue 2
Author(s): Małgorzata Krześniak, Dorota Butkiewicz, Jadwiga Rachtan, Iwona Matuszczyk, Ewa Grzybowska, Marek Rusin
PurposeLi-Fraumeni syndrome (LFS) is a rare genetic disease with strong predispositions to multiple early-onset neoplasms, mostly sarcomas, breast cancers, brain tumors and adrenocortical carcinomas (LFS core cancers). In most LFS families the germline mutations of TP53 tumor suppressor gene were found. Lung cancer does not belong to the core cancers of LFS, however its higher incidence is observed in families with TP53 mutations. Our aim was to search for TP53 mutations in female lung cancer patients whose clinico-demographic characteristics suggested a probable genetic predisposition to the disease.Materials and methodsThe coding region of TP53 from blood DNA was sequenced using Sanger method. The functioning of detected mutation was tested by luciferase reporter assay.ResultsWe found a nucleotide substitution c.569C>G, p.Pro190Arg, which was not described in the TP53 germline mutation database (http://ift.tt/2r44pEI). The mutation destroys the ability of p53 to transactivate BAX promoter and significantly reduces transactivation potential of p53 toward the promoter of MDM2 gen.ConclusionWe identified novel germline mutation of TP53.
http://ift.tt/2qumWgJ
Publication date: 2018
Source:Clinical Gynecologic Oncology
Author(s): Lisa M. Landrum, Rosemary E. Zuna, Joan L. Walker
http://ift.tt/2qucYvM
Publication date: 15 June 2017
Source:International Journal of Pharmaceutics, Volume 525, Issue 1
Author(s): Zimeng Wang, Sweta K. Gupta, Samantha A. Meenach
Biocompatible, biodegradable polymers are commonly used as excipients to improve the drug delivery properties of aerosol formulations, in which acetalated dextran (Ac-Dex) exhibits promising potential as a polymer in various therapeutic applications. Despite this promise, there is no comprehensive study on the use of Ac-Dex as an excipient for dry powder aerosol formulations. In this study, we developed and characterized pulmonary drug delivery aerosol microparticle systems based on spray-dried Ac-Dex with capabilities of (1) delivering therapeutics to the deep lung, (2) targeting the particles to a desired location within the lungs, and (3) releasing the therapeutics in a controlled fashion. Two types of Ac-Dex, with either rapid or slow degradation rates, were synthesized. Nanocomposite microparticle (nCmP) and microparticle (MP) systems were successfully formulated using both kinds of Ac-Dex as excipients and curcumin as a model drug. The resulting MP were collapsed spheres approximately 1μm in diameter, while the nCmP were similar in size with wrinkled surfaces, and these systems dissociated into 200nm nanoparticles upon reconstitution in water. The drug release rates of the Ac-Dex particles were tuned by modifying the particle size and ratio of fast to slow degrading Ac-Dex. The pH of the environment was also a significant factor that influenced the drug release rate. All nCmP and MP systems exhibited desirable aerodynamic diameters that are suitable for deep lung delivery (e.g. below 5μm). Overall, the engineered Ac-Dex aerosol particle systems have the potential to provide targeted and effective delivery of therapeutics into the deep lung.
Publication date: 2017
Source:Ferri's Clinical Advisor 2017
Author(s): Fred F. Ferri
http://ift.tt/2qualK7
This study aimed to investigate a potential modulatory effect of E. coli lipopolysaccharide (LPS) on the kinetics of deoxynivalenol (DON) and zearalenone (ZEN) after pre- or post-hepatic LPS administration to unravel the putative role of the liver. Fifteen barrows were fed a diet containing mycotoxin-contaminated maize (4.59 mg DON/kg feed, 0.22 mg ZEN/kg feed) for 29 days and equipped with pre-hepatic catheters (portal vein, "po") and post-hepatic catheters (jugular vein, "ju"), facilitating simultaneous infusion of LPS ("LPS group", 7.5 μg/kg body weight) or 0.9% sterile NaCl solution (control, "CON group", equivolumar to LPS group) and blood sampling. This resulted in three infusion groups, depending on infusion site: CONju-CONpo, CONju-LPSpo, and LPSju-CONpo. On day 29, pigs were fed their morning ration (700 g/pig) (−15 min), and blood samples were collected at regular intervals relative to infusion start. At 195 min, pigs were sacrificed and bile, urine, liquor, and liver samples collected. DON concentrations in jugular and portal blood decreased in both LPS-infused groups, whereas the ZEN concentrations increased, regardless of the treatment site. In liver tissue, a decrease of both toxin concentrations was observed in endotoxaemic pigs as well as a drop in hepatic conjugation, regardless of LPS entry site. In contrast to our hypothesis, DON and ZEN were not differently altered depending on the LPS-entry site. Neither the absorption nor the accumulation of DON and ZEN in different tissues differed significantly between animals which were infused with LPS via either the jugular or portal vein.
Teratomas are true neoplasms that contain tissues foreign to the site in which they arise. They are derived from germ cells with components of the three embryonic layers (ectoderm, mesoderm and endoderm). The present report is about a 10 day old neonate with teratoma arising from the nasopharyngeal surface of the soft palate, which was successfully removed.
Publication date: 2017
Source:Conn's Current Therapy 2017
Author(s): Edward T. Bope, Rick D. Kellerman
http://ift.tt/2r46v7I
Publication date: 2017
Source:Examination Medicine
Author(s): Nicholas J Talley, Simon O'Connor
http://ift.tt/2r48Kb6
Publication date: 2017
Source:Pediatric Primary Care
Author(s): Martha Driessnack, Sandra Daack-Hirsch
http://ift.tt/2qurmnw
Publication date: 2017
Source:Ferri's Clinical Advisor 2017
http://ift.tt/2r46DUz
Publication date: 2017
Source:Examination Medicine
Author(s): Nicholas J Talley, Simon O'Connor
http://ift.tt/2qudREl
Publication date: 2016
Source:Cardiovascular Intervention
Author(s): Nicolas W. Shammas
http://ift.tt/2qul5Ix
Publication date: 2017
Source:Ferri's Clinical Advisor 2017
Author(s): Fred F. Ferri
http://ift.tt/2qub7He
Publication date: 2017
Source:Ferri's Clinical Advisor 2017
Author(s): Fred F. Ferri
http://ift.tt/2r4agKw
Publication date: 2016
Source:Andrews' Diseases of the Skin
http://ift.tt/2r4jbM3
In this study, the levels of aflatoxin B1 (AFB1), ochratoxin A (OTA), zearalenone (ZEN), deoxynivalenol (DON) and fumonisins (FUM) in unprocessed cereals (n = 189) and cereal-based products (n = 61) were determined using validated ELISA methods. All samples originated from either conventional or organic production corresponded to the 2015 harvest in Croatia. Based on the mean mycotoxin concentrations, the risk for the consumer to exceed the tolerable daily intake (TDI) for these toxins by the consumption of both types of cereals and cereal-based products was assessed. Mycotoxin contamination of organic cereals and organic cereal-based products was not significantly different (p > 0.05). Given that the exposure assessment resulted in a small fraction of the TDI (maximum: DON, 12% of TDI), the levels of the investigated mycotoxins in both types of cereals and cereal-based products from the 2015 harvest did not pose a human health hazard.
The aim of the present study was to examine the role of chronic deoxynivalenol (DON) exposition on the liver morphology and function in combination with pre- and post-hepatic lipopolysaccharide (LPS) stress in young pigs fed for 4 weeks with a DON-contaminated diet (4.59 mg/kg feed). At the end of the experiment, LPS (7.5 μg/kg BW) was administered for 1 h pre-hepatically (Vena portae hepatis) or post-hepatically (Vena jugularis). Liver morphology was macroscopically checked and showed haemorrhage in all LPS groups, significantly higher relative liver weights, accompanied by marked oedema in the gallbladder wall. Histological changes were judged by a modified histology activity index (HAI). Liver HAI score was significantly increased in all LPS groups compared to placebo, primarily due to neutrophil infiltration and haemorrhage. DON feed alone was without effect on the liver HAI. Liver function was characterized by (i) hepatic biochemical markers, (ii) mitochondrial respiration and (iii) Ca2+ accumulation capacity of isolated mitochondria. Clinical chemical parameters characterizing liver function were initially (<3 h) slightly influenced by LPS. After 3 h, bilirubin and alkaline phosphatase were increased significantly, in DON-fed, jugular-infused LPS group. Respiration and Ca2+ accumulation capacity of isolated liver mitochondria was not impaired by chronic DON exposure, acute LPS challenge or combined treatments. DON-contaminated feed did not change macroscopy and histology of the liver, but modified the function under LPS stress. The different function was not linked to modifications of liver mitochondria.
Infections of maize with phytopathogenic and toxinogenic Fusarium spp. may occur throughout the cultivation period. This can cause different types of diseases in vegetative and generative organs of the plant. Along with these infections, mycotoxins are often produced and accumulated in affected tissues, which could pose a significant risk on human and animal health when entering the food and feed chain. Most important fungal species infecting European maize belong to the Fusarium sections Discolour and Liseola, the first being more prevalent in cooler and humid climate regions than the second predominating in warmer and dryer areas. Coexistence of several Fusarium spp. pathogens in growing maize under field conditions is the usual case and may lead to multi-contamination with mycotoxins like trichothecenes, zearalenone and fumonisins. The pathways how the fungi gain access to the target organs of the plant are extensively described in relation to specific symptoms of typical rot diseases regarding ears, kernels, rudimentary ears, roots, stem, leaves, seed and seedlings. Both Gibberella and Fusarium ear rots are of major importance in affecting the toxinogenic quality of grain or ear-based products as well as forage maize used for human or animal nutrition. Although rudimentary ears may contain high amounts of Fusarium toxins, the contribution to the contamination of forage maize is minor due to their small proportion on the whole plant dry matter yield. The impact of foliar diseases on forage maize contamination is regarded to be low, as Fusarium infections are restricted to some parts on the leaf sheaths and husks. Mycotoxins produced in rotted basal part of the stem may contribute to forage maize contamination, but usually remain in the stubbles after harvest. As the probability of a more severe disease progression is increasing with a prolonged cultivation period, maize should be harvested at the appropriate maturity stage to keep Fusarium toxin contamination as low as possible. Ongoing surveillance and research is needed to recognise changes in the spectrum of dominating Fusarium pathogens involved in mycotoxin contamination of maize to ensure safety in the food and feed chain.
