The use of oximetry and a questionnaire in primary care enables exclusion of a subsequent obstructive sleep apnea diagnosis.

PURPOSE: The study aims to prospectively validate the prognostic value of oximetry alone or combined in a two-step strategy with a questionnaire for the exclusion of obstructive sleep apnea (OSA) in primary care. METHODS: A total of 140 subjects with suspected OSA were included from 54 participating primary care practices. All subjects completed the Philips questionnaire and underwent one night of oximetry prior to referral to a sleep center. The prognostic value of two strategies was evaluated against the diagnosis of the sleep center as the gold standard: (1) assume OSA and subsequently refer to a sleep center if the oxygen desaturation index (ODI) is ≥ 5 and (2) assume OSA and refer to a sleep center if the Philips questionnaire score is ≥ 55% (regardless of the ODI) or if the Philips questionnaire score is < 55% and the ODI is ≥ 5. RESULTS: OSA was diagnosed in the sleep centers in 100 (71%) of the included subjects. Using ODI ≥ 5 alone resulted in a sensitivity of 99.0%, a specificity of 50.0%, a negative predictive value of 95.2%, and a positive predictive value 83.2%. Using the two-step strategy, oximetry would be performed on 39% of the subjects. This strategy resulted in a sensitivity of 100%, a specificity of 35.0%, a negative predictive value of 100%, and a positive predictive value of 79.4%. CONCLUSIONS: In a Dutch primary care population with a clinical suspicion of OSA and low frequency of cardiovascular comorbidities, the use of oximetry alone or combined in a two-step strategy with a questionnaire enables exclusion of a sleep center diagnosis of OSA.

Validation of the oxygen desaturation index in the diagnostic workup of obstructive sleep apnea.

INTRODUCTION: Obstructive sleep apnea (OSA) is common, and diagnosis requires expensive and laborious testing to assess the apnea hypopnea index (AHI). We performed an analysis to explore the relationship between the oxygen desaturation index (ODI) as measured with pulse oximetry and the AHI in our large portable monitoring (PM) database to find an optimal cutoff value for the ODI in order to be able to exclude AHI ≥ 5 on PM. METHODS: Three thousand four hundred thirteen PM recordings were randomly divided into a training set (N = 2281) and a test set (N = 1132). The optimal cutoff for the ODI to exclude an AHI ≥ 5 on PM was determined in the training set and subsequently validated in the test set. RESULTS: Area under the curve of the ODI to exclude an AHI ≥ 5 on PM was 0.997 in the training set and 0.996 in the test set. In the training set, the optimal cutoff to predict an AHI < 5 was an ODI < 5. Using this cutoff in the test set provided a sensitivity of 97.7%, a specificity of 97.0%, a positive predictive value of 99.2%, and a negative predictive value of 91.4%. CONCLUSION: An ODI < 5 predicts an AHI < 5 with high sensitivity and specificity when measured simultaneously using the same oximeter during PM recording.

Challenges in the implementation of EAACI guidelines on allergen immunotherapy: A global perspective on the regulation of allergen products.

Regulatory approaches for allergen immunotherapy (AIT) products and the availability of high-quality AIT products are inherently linked to each other. While allergen products are available in many countries across the globe, their regulation is very heterogeneous. First, we describe the regulatory systems applicable for AIT products in the European Union (EU) and in the United States (US). For Europe, a depiction of the different types of relevant procedures, as well as the committees involved, is provided and the fundamental role of national agencies of the EU member states in this complex and unique network is highlighted. Furthermore, the regulatory agencies from Australia, Canada, Japan, Russia, and Switzerland provided information on the system implemented in their countries for the regulation of allergen products. While AIT products are commonly classified as biological medicinal products, they are made available by varying types of procedures, most commonly either by obtaining a marketing authorization or by being distributed as named patient products. Exemptions from marketing authorizations in exceptional cases, as well as import of allergen products from other countries, are additional tools applied by countries to ensure availability of needed AIT products. Several challenges for AIT products are apparent from this analysis and will require further consideration.

Allergen manufacturing and quality aspects for allergen immunotherapy in Europe and the United States: An analysis from the EAACI AIT Guidelines Project.

Adequate quality is essential for any medicinal product to be eligible for marketing. Quality includes verification of the identity, content and purity of a medicinal product in combination with a specified production process and its control. Allergen products derived from natural sources require particular considerations to ensure adequate quality. Here, we describe key aspects of the documentation on manufacturing and quality aspects for allergen immunotherapy products in the European Union and the United States. In some key parts, requirements in these areas are harmonized while other fields are regulated separately between both regions. Essential differences are found in the use of Reference Preparations, or the requirement to apply standardized assays for potency determination. As the types of products available are different in specific regions, regulatory guidance for such products may also be available in one specific region only, such as for allergoids in the European Union. Region-specific issues and priorities are a result of this. As allergen products derived from natural sources are inherently variable in their qualitative and quantitative composition, these products present special challenges to balance the variability and ensuring batch-to-batch consistency. Advancements in scientific knowledge on specific allergens and their role in allergic disease will consequentially find representation in future regulatory guidelines.

Proposals for harmonization of allergens regulation in the European Union.

Allergen medicinal products in the European Union are regulated differently across the different Member States. Thus, whereas in some countries strict quality, safety and efficacy requirements are in place, in others, most allergens are on the market as Named Patient Products, without any regulatory oversight. This situation results on European allergic patients being exposed to totally different standards depending on where they live. Initiatives to correct this situation are needed.

Learning about informal fallacies and the detection of fake news: An experimental intervention.

The philosophical concept of informal fallacies-arguments that fail to provide sufficient support for a claim-is introduced and connected to the topic of fake news detection. We assumed that the ability to identify informal fallacies can be trained and that this ability enables individuals to better distinguish between fake news and real news. We tested these assumptions in a two-group between-participants experiment (N = 116). The two groups participated in a 30-minute-long text-based learning intervention: either about informal fallacies or about fake news. Learning about informal fallacies enhanced participants' ability to identify fallacious arguments one week later. Furthermore, the ability to identify fallacious arguments was associated with a better discernment between real news and fake news. Participants in the informal fallacy intervention group and the fake news intervention group performed equally well on the news discernment task. The contribution of (identifying) informal fallacies for research and practice is discussed.

Ileosigmoid Knotting: A Case Series.

Ileosigmoid knotting is a rare case of intestinal obstruction that later leads to bowel necrosis. This is more common in males than females and seen more in areas with increased rates of sigmoid volvulus. The main clinical presentations are abdominal distention, abdominal pain and tenderness, vomiting, and obstipation. Definitive diagnosis is challenging due to its rarity and overlapping symptoms with other more common abdominal conditions. Delay in diagnosis and management can lead to peritonitis, necrosis of the bowel, sepsis, and eventually septic shock. Surgeons should consider ileosigmoid knotting in cases of acute abdomen, as it requires fast decision-making and intervention for a good prognosis. We present two cases of ileosigmoid knotting presenting with acute abdomen requiring emergent laparotomy with resection of necrotic bowel.

Expression and function of a variant T cell receptor complex lacking CD3-gamma.

A T cell line termed DIL2 has been derived from an infant with a polyclonal T cell receptor (TCR)/CD3 cell surface expression defect. Indirect immunofluorescence showed that the expression of certain TCR/CD3 epitopes (like those detected by WT31 and BMA031 monoclonals) was strongly reduced (around five-fold) on DIL2, whereas other epitopes (like those detected by SP34 and Leu4) were only around two-fold lower than in normal T cell lines. Specific immunoprecipitates of surface-radioiodinated DIL2 cells contained TCR-alpha, TCR-beta, CD3-delta, CD3-epsilon and TCR-zeta chains, but lacked CD3-gamma. This structural TCR/CD3 variant was, however, capable of transducing certain activation signals, since normal proliferation and a low but significant calcium flux was observed in DIL2 cells after engagement with specific antibodies. Our data suggest that a functional TCR/CD3 complex can be expressed on the surface of T cells in the absence of CD3-gamma.

Effect of different cooking methods on lipid oxidation and formation of free cholesterol oxidation products (COPs) in Latissimus dorsi muscle of Iberian pigs.

The aim of this work was to study the influence of different cooking methods (grilled (GR), fried (FP), microwave (MW) and roasted (RO)) on lipid oxidation and formation of free cholesterol oxidation products (COPs) of meat from Iberian pigs that have been fed on an intensive system. Moisture and total lipid content, TBARs, hexanal and COPs were measured in Latissimus dorsi muscle samples. Cooking did not produce changes in total lipid content in meat but induced significantly higher lipid oxidation (TBARs and hexanal values) (p<0.001) and cholesterol oxidation (COPs) (p<0.01). When the different cooking methods were studied, the grilled method was the least affected by lipid oxidation (TBARs and hexanal) compared to the others. There were no significant differences among different cooking methods on COPs values. The most abundant cholesterol oxides were both 7α-hydroxycholesterol and 7ß-hydroxycholesterol in all groups studied.

Longitudinal analysis of cytokine gene expression and parasite load in PBMC in Leishmania infantum experimentally infected dogs.

Canine visceral leishmaniasis (CVL) is caused by Leishmania infantum, an intracellular protozoan parasite that causes a severe infectious disease. To evaluate the gene expression profile associated to CVL in vivo, we have measured monthly by real-time PCR over one year the IL-4, IL-10, IL-12, IL-13, IFN-gamma, TGF-beta and TNF-alpha mRNA levels in peripheral blood mononuclear cells in 6 experimentally infected dogs that exhibited different progressions of the illness. While in two dogs no parasite, or a very low number of parasites, was detected and the two dogs did not show any clinico-pathological abnormalities at the end of the study (L dogs), for the remaining dogs high parasite loads were detected and they developed clinical leishmaniasis (H dogs). The L dogs have null expression of both IL-4 and IL-13 for the first 4 months after the infection, whereas an early IL-4 and IL-13 expression occurs in this period of infection in most of the dogs that developed clinical leishmaniasis (H dogs). Furthermore, a higher IFN-gamma expression was associated with the increase of parasite load and clinical status in these dogs. Moreover, the high variability of expression at the pre-infection stage causes us to reject the possibility that the basal levels of these cytokines indicate the prognosis of the subsequent response against infection.

Reproducibility of hypercapnic ventilatory response measurements with steady-state and rebreathing methods.

In this study, the hypercapnic ventilatory response (HCVR) was measured, defined as the ventilation response to carbon dioxide tension (PCO2 ). We investigated which method, rebreathing or steady-state, is most suitable for measurement of the HCVR in healthy subjects, primarily based on reproducibility. Secondary outcome parameters were subject experience and duration. 20 healthy adults performed a rebreathing and steady-state HCVR measurement on two separate days. Subject experience was assessed using numeric rating scales (NRS). The intraclass correlation coefficient (ICCs) of the sensitivity to carbon dioxide above the ventilatory recruitment threshold and the projected apnoea threshold were calculated to determine the reproducibility of both methods. The ICCs of sensitivity were 0.89 (rebreathing) and 0.56 (steady-state). The ICCs of the projected apnoea threshold were 0.84 (rebreathing) and 0.25 (steady-state). The steady-state measurement was preferred by 16 out of 20 subjects; the differences in NRS scores were small. The hypercapnic ventilatory response measured using the rebreathing setup provided reproducible results, while the steady-state method did not. This may be explained by high variability in end-tidal PCO2 . Differences in subject experience between the methods are small.

Retrospective validation of a new volumetric capnography parameter for the exclusion of pulmonary embolism at the emergency department.

Volumetric capnography might be used to exclude pulmonary embolism (PE) without the need for computed tomography pulmonary angiography. In a pilot study, a new parameter (CapNoPE) combining the amount of carbon dioxide exhaled per breath (carbon dioxide production (V CO2 )), the slope of phase 3 of the volumetric capnogram (slope 3) and respiratory rate (RR) showed promising diagnostic accuracy (where CapNoPE=(V CO2 ×slope 3)/RR). To retrospectively validate CapNoPE for the exclusion of PE, the volumetric capnograms of 205 subjects (68 with PE) were analysed, based on a large multicentre dataset of volumetric capnograms from subjects with suspected PE at the emergency department. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve and diagnostic accuracy of the in-pilot established threshold (1.90 Pa·min) were calculated. CapNoPE was 1.56±0.97 Pa·min in subjects with PE versus 2.51±1.67 Pa·min in those without PE (p<0.001). The AUC of the ROC curve was 0.714 (95% CI 0.64-0.79). For the cut-off of ≥1.90 Pa·min, sensitivity was 64.7%, specificity was 59.9%, the negative predictive value was 77.4% and the positive predictive value was 44.4%. The CapNoPE parameter is decreased in patients with PE but its diagnostic accuracy seems too low to use in clinical practice.

Food by-products as potential antioxidant and antimicrobial additives in chill stored raw lamb patties.

The aim of this work was to study the in vitro antioxidant potential of aqueous extracts obtained from tomato (TOM), red grape (GRA), olive (OLI) and pomegranate (POM) by-products as well as to evaluate the effect of their addition into lamb meat patties (1000mg/kg) in order to improve shelf life. A negative (CON) and a positive control (sodium ascorbate, ASC) were also included in the experiment. Results for radical scavenging activity, metal chelating activity and reducing power indicated that GRA and OLI extracts could inhibit oxidation more efficiently than POM and TOM extracts (P<0.01). Consistently, GRA and OLI treatments showed the highest redness (a*) (P<0.01) and antioxidant activity, both for lipids and proteins, throughout storage (P<0.001). Furthermore, in general, microbial counts were reduced by the addition of by-products extracts. These results suggest that the extracts obtained from grape and olive pomaces could be effectively used to replace sodium ascorbate in lamb meat products.

The TL,NO /TL,CO ratio cannot be used to exclude pulmonary embolism.

BACKGROUND: The existing screening modalities for pulmonary embolism (PE), such as D-dimer and clinical prediction rules, have low positive predictive values. With its capability to indicate pulmonary vascular abnormalities, the ratio of the transfer factor of the lungs for nitric oxide and the transfer factor of the lungs for carbon monoxide (TL,NO /TL,CO ) might be an additional discriminating parameter. METHODS: Carbon monoxide/Nitric oxide diffusion measurements were performed on unselected patients seen on the emergency department for which due to suspected PE a computed tomography pulmonary angiogram (CTPA) was ordered. RESULTS: A total of 28 patients were included, PE was found in 12 on CTPA. Median TL,NO /TL,CO ratio was 4·09 (interquartile range (IQR) 3·83-4·40) in the no PE group versus 4·00 (IQR 3·78-4·32) in the PE group (P = 0·959). Median alveolar volume was 77·1% of predicted in the no PE group versus 71·0% of predicted in the PE group (P = 0·353). Median TL,CO was 75·8% of predicted in the no PE group versus 68·8% of predicted in the PE group (P = 0·120). Median TL,NO was 69·3% of predicted in the no PE group versus 60·5% of predicted in the PE group (P = 0·078). CONCLUSION: The presented data indicate that the TL,NO /TL,CO ratio cannot be used to exclude PE.

Volumetric capnography in the exclusion of pulmonary embolism at the emergency department: a pilot study.

The analysis of the [Formula: see text] in expired air as a function of the exhaled volume (volumetric capnography) might result in a more specific exclusion tool for pulmonary embolism (PE) in addition to the Wells-score and D-dimer. A novel combination of volumetric capnography parameters ([Formula: see text]) should be decreased in PE and could possibly be used to decrease the number of requested computed tomography pulmonary angiograms (CTPA). Volumetric capnography measurements were performed on consecutive patients seen in the emergency department for which, due to suspected PE (due to increased D-dimer level or Wells-score), a CTPA was ordered. A total of 30 subjects were included, of which in 13 PE was seen on CTPA. Median [Formula: see text] was 4.36 kPa (IQR 3.92-4.88) in the no PE group versus 4.07 kPa (IQR 3.37-4.39) in the PE group (p = 0.086). Median of the novel parameter [Formula: see text] was 1.85 min.kPa dl-1 (IQR 1.21-3.00) in the no PE group versus 1.18 min.kPa dl-1 (IQR 0.61-1.38) in the PE group (p = 0.006). Using a threshold for the new parameter of 1.90 min.kPa dl-1 or higher to exclude PE resulted in a negative predictive value of 100% (95% CI: 77%-100%) and would have potentially excluded PE in 47% (95% CI: 26%-69%) of the no PE group without the need for CTPA. This pilot study introduces a novel parameter [Formula: see text] which is significantly decreased in PE subjects. Future studies regarding validation and addressing aspects such as reproducibility and normalization after treatment are needed to confirm its usability in excluding PE in the emergency department.

Herpes virus saimiri transformation of T cells in CD3 gamma immunodeficiency: phenotypic and functional characterization.

The characterization of T cell immunodeficiencies could in part be supported by using stable cell lines in which biochemical and molecular studies of the defect could be carried out thereby omitting frequent bleeding of patients. First attempts to obtain such cell lines included HTLV-I transformation and exogenous IL-2 administration, but both models have important disadvantages. Recently, a virus isolated from the squirrel monkey, Herpes virus saimiri (HVS), has been reported to have the ability to transform T cells. A stable IL-2-dependent HVS-transformed T cell line from a CD3 gamma deficient patient has been obtained; and this cell line displays both the phenotypic and the functional characteristics of the patient's lymphocytes. Moreover, the line down-modulates TCR/CD3 surface expression upon CD3 engagement, as do the patient's lymphocytes, showing that CD3 gamma and its phosphorylation are not necessary for TCR/CD3 internalization. In addition, the abnormal staining pattern of different anti-TCR/CD3 monoclonal antibodies is preserved in the HVS-patient line. Since HVS is capable of transforming CD3 gamma- T cells, the CD3 gamma chain does not seem to be involved in the HVS receptor process. The fact that it is not possible to obtain a CD8+ HVS line from the CD3 gamma- patient supports the existence of a functional anomaly in his scanty CD8+ peripheral lymphocytes. Thus, HVS transformation is a suitable model for T cell immunodeficiency studies and characterization. It may also be used in the future in cellular models for in vitro gene therapy trials.

Peripheral blood reduction of memory (CD29+, CD45RO+, and "bright" CD2+ and LFA-1+) T lymphocytes in Papillon-Lefèvre syndrome.

A Papillon-Lefèvre patient with characteristic chronic periodontal disease and palmoplantar keratoderma was studied over a 4-year period. An abnormal T-cell phenotype was steadily observed in peripheral blood; both low numbers of CD29+ and CD45RO+ cells and a low density surface expression of CD2 and LFA-1 molecules were found. T-cell activation through CD3, CD2 and ConA, PWM and IL-2 receptors was normal; however, there was impairment in the activation via CD28. CD2, LFA-1 and CD45 molecules were normal in charge and molecular weight. There was no tissue sequestering of T lymphocytes in periodontal lesions, but rather a relative T-cell reduction. It is suggested that an important decrease of the so-called "memory/hyperreactive" (CD45RO-positive) T cells does exist; therefore, hyperreactive T cells would not be available in sufficient numbers to leave the bloodstream through blood vessel endothelium, and the periodontium would be left without these important defenses and thus exposed to chronic infections. A disregulated factor affecting the transition from "naive" to "memory" T cells and the increase in certain surface molecules expression (i.e., CD2, LFA-1, CD29, and CD45RO) or the reversion from memory to naive T cells may be responsible for the disease pathogenesis. CD2 and LFA-1 molecule synthesis might be conjointly regulated on T lymphocytes.

Subcutaneous and intermuscular fat characterisation of dry-cured Iberian hams.

The fatty acid composition of the triacylglycerols and free fatty acids of subcutaneous (internal and superficial layers) and intermuscular fat and the contribution of these fatty acids to the formation of volatile compounds were determined in dry-cured Iberian ham. The profile of the fatty acids and volatile compounds showed that lipolytic and oxidative processes occur more intensively in subcutaneous than intermuscular fat, however, few differences were found compared to those found in ham lean.

Evolution of volatile aldehydes in Iberian ham matured under different processing conditions.

To evaluate the influence of the Iberian ham processing conditions in the evolution of volatile aldehydes, 35 hams were processed in two plants following different conditions of relative humidity and temperature. For this, free fatty acids, peroxide values and volatile aldehydes were quantified in the hams. The highest increases in free fatty acids were noted during the drying stage in both processing plants. The drying period also revealed the greatest increase in peroxide values, where the highest values were in those hams processed at higher temperatures. The temperature during post-salting and drying had a marked influence on the formation of volatile aldehydes, being responsible for the differences in volatile compounds of matured hams.

In situ transesterification of fatty acids from Iberian pig subcutaneous adipose tissue.

The purpose of this study was to optimize a rapid method for fatty acid analysis in Iberian pig subcutaneous adipose tissue. An in situ transesterification method was used to avoid the lengthy lipid extraction step. Samples were in situ transesterified with 5% HCl/methanol at 70°C, and toluene was used to help dissolve lipids. The method had advantages over other in situ methods since only 45 min were required to completely transesterify the fatty acids, and 10 min to obtain the fatty acid profile. A sample size of 25 mg of adipose tissue was suitable. The in situ transesterification gave higher fatty acid concentrations than conventional lipid extraction and transesterification, the differences being significant for all the fatty acids. Relative fatty acid contents were similar to those found by the conventional method.