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Reports on the medical case of a 28-year-old woman with fixed drug eruption from quinolones with a positive lesional patch test to ciprofloxacin. Development of pruritic erythematous macules on the dorsum of both hands; Prick test results; Clinical cross-sensitivity between norfloxacin and ciprofloxacin.

Zygophyllum fabago is a herbaceous plant found widely in the Mediterranean area. There are no previous reports of its allergenicity. An aerobiologic and clinical survey was conducted in Murcia, southern Spain, to determine the quantity of airborne pollen and establish the possible role of this pollen as a cause of allergic symptoms. With a Hirst volumetric trap, we determined the atmospheric concentrations of this pollen in 1993, 1994,1995, and 1996. Of 1180 patients tested, 181 (15,34%) had a positive skin test. To determine its allergenicity, we divided 47 patients into three groups: in group 1, all the patients had symptoms of rhinoconjunctivitis plus asthma; in groups 2 and 3, rhinoconjunctivitis. In group 1, we performed a bronchial provocation test (BPT): in groups 2 and 3, we performed nasal provocation (NPT) and conjunctival provocation (CPT) tests, respectively, SDS-PAGE was used to characterize the antigenic fractions and RAST inhibition to determine cross-reactivity with other pollens. The pollen dispersion period is from May to September (445 grains/m³), BPT was positive in 13 of 15 patients, NPT in 14 of 16 patients, and CPT in 13 of 16 patients. RAST inhibition revealed cross-reactivity with Mercurialis, Ricinus, Olea, and Betula. SDS-PAGE identified 25 IgE antibody-binding components, five of which (60, 65, 41, 38, and 15.5/14,7 kDa) were recognized by 40% of the sera. By SDS-PAGE immunoblotting with sunflower antiprofilin rabbit serum and affinity chromatography we established that the Z. fabago extract has profilin. This study shows that this pollen becomes airborne and elicits an IgE response which triggers respiratory symptoms in allergic subjects. [ABSTRACT FROM AUTHOR]

Background: The mineralocorticoid receptor plays a significant role in the development of chronic kidney disease (CKD) and associated cardiovascular complications. Classic steroidal mineralocorticoid receptor antagonists are a therapeutic option, but their use in the clinic is limited due to the associated risk of hyperkalemia in patients with CKD. Finerenone is a nonsteroidal mineralocorticoid receptor antagonist that has been recently investigated in 2 large phase III clinical trials (FIDELIO-DKD [Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease] and FIGARO-DKD [Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease]), showing reductions in kidney and cardiovascular outcomes., Methods and Results: We tested whether finerenone improves renal and cardiac function in a preclinical nondiabetic CKD model. Twelve weeks after 5/6 nephrectomy, the rats showed classic signs of CKD characterized by a reduced glomerular filtration rate and increased kidney weight, associated with left ventricular (LV) diastolic dysfunction and decreased LV perfusion. These changes were associated with increased cardiac fibrosis and reduced endothelial nitric oxide synthase activating phosphorylation (ser 1177). Treatment with finerenone prevented LV diastolic dysfunction and increased LV tissue perfusion associated with a reduction in cardiac fibrosis and increased endothelial nitric oxide synthase phosphorylation. Curative treatment with finerenone improves nondiabetic CKD-related LV diastolic function associated with a reduction in cardiac fibrosis and increased cardiac phosphorylated endothelial nitric oxide synthase independently from changes in kidney function. Short-term finerenone treatment decreased LV end-diastolic pressure volume relationship and increased phosphorylated endothelial nitric oxide synthase and nitric oxide synthase activity., Conclusions: We showed that the nonsteroidal mineralocorticoid receptor antagonist finerenone reduces renal hypertrophy and albuminuria, attenuates cardiac diastolic dysfunction and cardiac fibrosis, and improves cardiac perfusion in a preclinical nondiabetic CKD model.

Objective: To evaluate the volumetric changes on occlusal surface of computer-aided design and computer-aided manufacturing (CAD-CAM) occlusal devices fabricated following a fully digital workflow after occlusal adjustment, compared to those fabricated with an analog workflow., Materials and Methods: Eight participants were included in this clinical pilot study, receiving two different occlusal devices fabricated with two different workflows, fully analog and fully digital. Every occlusal device was scanned before and after the occlusal adjustments to compare the volumetric changes using a reverse engineering software program. Moreover, three independent evaluators assessed a semi-quantitative and qualitative comparison using visual analog scale and dichotomous evaluation. The Shapiro-Wilk test was performed to validate normal distribution assumption, and a dependent t-Student test for paired variables was used to determine statistically significant differences (p-value < 0.05)., Results: The root mean square value was extracted from the 3-Dimensional (3D) analysis of the occlusal devices. The average values of the root mean square were higher for the analogic technique (0.23 ± 0.10 mm) than the digital technique (0.14 ± 0.07 mm) but the differences were not statistically significant (paired t-Student test; p = 0.106) between the two fabrication techniques. The semiquantitative visual analog scale values between the impression for the digital (5.08 ± 2.4 cm) and analog (3.80 ± 3.3 cm) technique were significant (p < 0.001), and statistically significant differences values were assessed for evaluator 3 compared to the other evaluators (p < 0.05). However, the three evaluators agreed on the qualitative dichotomous evaluation in 62% of the cases, and at least two evaluators agreed in 100% of the evaluations., Conclusions: Occlusal devices fabricated following a fully digital workflow resulted in fewer occlusal adjustments, as they could be a valid alternative to those fabricated following an analog workflow., Clinical Significance: Fabricated occlusal devices following a fully digital workflow could have some advantages over analog workflow such reduce occlusal adjustments at delivery appointment, which can result in reduced chair time and therefore increased comfort for the patient and clinician., (© 2023 The Authors. Journal of Esthetic and Restorative Dentistry published by Wiley Periodicals LLC.)

Objective: This clinical trial aims to compare the accuracy of interocclusal registration in centric relation taken with polyvinyl siloxane and intraoral scanner (IOS) with the fabrication of occlusal devices., Methods: Thirty-one participants were included in the trial registered at ClinicalTrials.gov (NCT05317182) receiving two different occlusal devices from two different workflows. One workflow was performed using polyvinyl siloxane impression material and the other with IOS. Every splint was scanned before and after the occlusal adjustments to compare the volumetric changes using the Root Mean Square deviation (RMS). Furthermore, three evaluators assessed the 3D comparison using color maps in a Visual Analog Scale (VAS)., Results: The average values of RMS were higher for the analog approach (0.01 ± 0.067) than the digital approach (0.065 ± 0.035). However, the differences were not statistically significant (p < 0.063) between the two impression techniques. For the semiquantitative analysis performed by blinded evaluators, differences in VAS values between the impression for the digital (2.08 ± 2.4) and analog (3.80 ± 3.3) technique were statistically significant. The three evaluators agreed in more than 90% of the qualitative dichotomous evaluation., Conclusion: Digital impressions did not show inferior accuracy compared to conventional impressions when assessed using quantitative measurements., Clinical Significance: This clinical trial provided evidence on registering interocclusal relationship at increased vertical dimension with fully digital workflow for complete arch prosthesis., (© 2023 Wiley Periodicals LLC.)

Objective: This study was aimed at identifying differences in the prodromal symptoms and their duration, risk factors and markers of vulnerability in patients presenting a first episode mania (FEM) or psychosis (FEP) with onset in late adolescence or adulthood in order to guide tailored treatment strategies., Methods: Patients with a FEM or FEP underwent a clinical assessment. Prodromes were evaluated with the Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R). Chi-squared tests were conducted to assess specific prodromal symptoms, risk factors or markers of vulnerability between groups. Significant prodromal symptoms were entered in a stepwise forward logistic regression model. The probabilities of a gradual versus rapid onset pattern of the prodromes were computed with logistic regression models., Results: The total sample included 108 patients (FEM = 72, FEP = 36). Social isolation was associated with the prodromal stage of a FEP whilst Increased energy or goal-directed activity with the prodrome to a FEM. Physically slowed down presented the most gradual onset whilst Increased energy presented the most rapid. The presence of obstetric complications and difficulties in writing and reading during childhood were risk factors for FEP. As for markers of vulnerability, impairment in premorbid adjustment was characteristic of FEP patients. No specific risk factor or marker of vulnerability was identified for FEM., Conclusion: Early characteristics differentiating FEP from FEM were identified. These findings might help shape early identification and preventive intervention programmes., (© 2022 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

In controlled human infection studies (CHIs), participants are deliberately exposed to infectious agents in order to better understand the mechanism of infection or disease and test therapies or vaccines. While most CHIs have been conducted in high-income countries, CHIs have recently been expanding into low- and middle-income countries (LMICs). One potential ethical concern about this expansion is the challenge of obtaining the voluntary informed consent of participants, especially those who may not be literate or have limited education. In some CHIs in LMICs, researchers have attempted to address this potential concern by limiting access to literate or educated populations. In this paper, we argue that this practice is unjustified, as it does not increase the chances of obtaining valid informed consent and therefore unfairly excludes illiterate populations and populations with lower education. Instead, we recommend that investigators improve the informed consent process by drawing on existing data on obtaining informed consent in these populations and interventions aimed at improving their understanding. Based on a literature review, we provide concrete suggestions for how to follow this recommendation and ensure that populations with lower literacy or education are given a fair opportunity to protect their rights and interests in the informed consent process., (© 2020 John Wiley & Sons Ltd.)

Background: NADPH Oxidase 5 (Nox5) is a calcium-sensitive superoxide-generating Nox. It is present in lower forms and higher mammals, but not in rodents. Nox5 is expressed in vascular cells, but the functional significance remains elusive. Given that contraction is controlled by calcium and reactive oxygen species, both associated with Nox5, we questioned the role of Nox5 in pro-contractile signaling and vascular function., Methods and Results: Transgenic mice expressing human Nox5 in a vascular smooth muscle cell-specific manner (Nox5 mice) and Rhodnius prolixus , an arthropod model that expresses Nox5 endogenoulsy, were studied. Reactive oxygen species generation was increased systemically and in the vasculature and heart in Nox5 mice. In Nox5-expressing mice, agonist-induced vasoconstriction was exaggerated and endothelium-dependent vasorelaxation was impaired. Vascular structural and mechanical properties were not influenced by Nox5. Vascular contractile responses in Nox5 mice were normalized by N -acetylcysteine and inhibitors of calcium channels, calmodulin, and endoplasmic reticulum ryanodine receptors, but not by GKT137831 (Nox1/4 inhibitor). At the cellular level, vascular changes in Nox5 mice were associated with increased vascular smooth muscle cell [Ca 2+ ] i , increased reactive oxygen species and nitrotyrosine levels, and hyperphosphorylation of pro-contractile signaling molecules MLC20 (myosin light chain 20) and MYPT1 (myosin phosphatase target subunit 1). Blood pressure was similar in wild-type and Nox5 mice. Nox5 did not amplify angiotensin II effects. In R. prolixus , gastrointestinal smooth muscle contraction was blunted by Nox5 silencing, but not by VAS2870 (Nox1/2/4 inhibitor)., Conclusions: Nox5 is a pro-contractile Nox isoform important in redox-sensitive contraction. This involves calcium-calmodulin and endoplasmic reticulum-regulated mechanisms. Our findings define a novel function for vascular Nox5, linking calcium and reactive oxygen species to the pro-contractile molecular machinery in vascular smooth muscle cells., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Unlabelled: The modern removable partial denture (RPD), in response to the increased esthetic demands of our patients, is no longer acceptable if it requires visible buccal and facial clasp arms for retention. By eliminating the bracing arm and having its functions taken by paralleled guide planes and precise, positive rests, the retentive element, a lingual circumferential wire clasp arm, will provide the same amount of retentive force as if it were placed on the buccal surface and will not be visible. Designs for the major connector either plate the lingual surface of the abutment or, as in a lingual bar, leave that surface open. Both of these situations are adaptable to the lingual retentive clasp and are illustrated in this article., Clinical Significance: Design features such as metal clasps needed for the retention of RPDs can be very unsightly, creating an esthetic problem. This article reviews the concepts for creating lingual clasp arms that enhance the esthetic quality of prostheses.

Background: Meat allergy is rarely reported. Most of the described cases are sensitizations to bovine serum albumin., Objective: The aim of the study was to describe a case of allergy to a new meat allergen and, after its characterization., Methods: A 35-year-old nonatopic female with allergic episodes after ingestion of several types of meat was studied. Skin tests (prick and prick-to-prick); total and specific immunoglobulin E (IgE) determination; sodium dodecyl sulphate-polyacrylamide gel electrophoresis and specific IgE determination by immunoblotting under different conditions were performed. A 17-kDa allergen was semipurified by ethanol fractionation and its amino-terminal sequence was determined. The existence of specific IgE directed to this protein was studied by immunoblot in 80 atopic patients., Results: The patient showed specific IgE antibodies to a 17-kDa protein. During the isolation of this allergen it was found that a 70-90% (vol/vol) ethanol concentration was able to purify the protein. The characterization revealed that it was a heat-resistant protein without disulfide bonds. N-terminal amino acid sequence (16 residues) showed identity with myoglobin. The study of specific IgE to this allergen among atopic patients showed that it was recognized by about 1% of the subjects., Conclusions: We describe a case of meat allergy caused by myoglobin. This is the first described case of monosensitization to this protein.

Background: Ole e 1 has been considered the major allergen of olive (Olea europaea) pollen. Some other relevant allergens (Ole e 2, 3, 4, and 6) have been recently described. This work aimed to study the IgE-binding frequency of a 36-kDa protein from O. europaea pollen in a large population of olive-allergic patients, its allergenic reactivity in vivo, and its presence in olive pollens of different origin, as well as in other relevant allergenic pollens., Methods: Identification of IgE-binding components from O. europaea pollen extracts was elucidated by inhibition of SDS-PAGE immunoblotting using recombinant profilin (Ole e 2) and Ole e 1 molecules. The IgE-binding frequency of the 36-kDa protein was estimated by Western blot in a sample of 120 sera from olive-allergic patients. The cutaneous test with the 36-kDa protein was performed by intradermoreaction in allergic patients and control subjects., Results: Exactly 83% of the sera from O. europaea-allergic patients recognized a protein with an apparent molecular weight of 36 kDa, under reducing conditions. It was detected by sera from monosensitized and polysensitized patients, showing a higher IgE frequency than the major allergen Ole e 1 (59%) and the minor profilin (Ole e 2) allergen (27%). Similar reactivity rates (79%) was found by intradermal test. Extracts from olive pollens collected in California presented a much higher amount (around 16-fold on average) of the 36-kDa protein than those from pollens of Spanish origin. The presence of similar allergens was detected only in closely related species (Syringa, Fraxinus, Ligustrum), and not in other common allergenic pollens., Conclusions: The 36-kDa protein constitutes a major allergen for olive-sensitized patients, but it is not equally represented in O. europaea pollens of different origins.

Sensitization to the flower of saffron, a plant commonly grown in Spain for commercial purposes, and its clinical significance as an occupational allergen were studied. The prick test and RAST, with saffron pollen, stamen, and pistil extracts, were used to evaluate the cutaneous and specific antibody responses in the studied population. Provocation tests in patients with clinical findings were used to verify the implication of saffron components in these symptoms. Fifty saffron workers were evaluated. Three of them were sensitized to saffron pollen and stamen proteins, giving prick and RAST positive values. One patient presented asthma, showing a positive bronchial provocation test, and two patients rhinoconjunctivitis, showing positive conjunctival provocation tests. Of a general allergic population of 237, 10 patients also presented cutaneous test and IgE positive to saffron. Saffron allergens (from pollen and stamens) were characterized by SDS-PAGE immunoblotting. A relevant allergen of 15.5 kDa with profilinic nature was detected and further purified by high-resolution gel filtration chromatography. No allergenic components were demonstrated in pistils. Cross-reactivity of saffron extracts was evaluated by RAST inhibition with respect to other pollen species commonly causing sensitization in the same area of study. A significant degree of cross-reactivity was demonstrated between saffron and Lolium, Salsola, or Olea. The identification of the protein components involved in the cross-reactions was investigated by blot inhibition.

A method based on ion-exchange column chromatography to enhance the protein content of fruit allergenic extracts was found to help make the subsequent SDS-PAGE immunoblotting assays possible; otherwise, they were difficult to achieve due to the high carbohydrate content. Fractionated extracts of apple, pear, and peach (peel and pulp) were obtained by anion-exchange chromatography (Q-Sepharose column), providing clear electrophoretic patterns which allowed IgE detection by enzymatic assays of the transferred membranes. This chromatographic method produced in one single step an enriched extract directly from the standard crude aqueous one, with an increment in the protein content of more than sixfold, on average; thus, it proved to be more suitable than the usual chemical fractionation procedures.

Four different commercially available raw materials of dog epithelia (dander, hair and skin scraping, skin scraping, and whole skin) were compared by means of biochemical methods such as SDS-PAGE and chromatography with the SMART System, immunochemical methods such as RAST and SDS-PAGE immunoblotting, and cutaneous tests. Dander extract clearly exhibited the highest IgE binding and in vivo allergenic activity. The dog major allergens Can fI and the 19-kDa protein were adequately detected only in dander extract. Thus, it is concluded that dander is the most suitable epithelial source for preparing dog allergenic extracts.

Human T cells are capable of forming rosettes with autologous erythrocytes (Tar cells) and behave as postthymic precursors. Thus, they generate Tgamma and Tmu cells as well as suppression and spontaneous cytotoxicity and participate in a pokeweed mitogen-driven system akin to that of feedback inhibition in which murine postthymic precursors participate. Tar cells were increased in 7 patients with mixed connective tissue disease (MCTD) compared to normal age/sex-matched controls. Despite this increase of precursor cells, decreased Tgamma cells and abrogation in the generation of suppression and of feedback inhibition were noted. These functional defects were not correctable with serum thymic factor but could be corrected by the addition of either allogenic Tmu or mononuclear cells depleted of Tar cells. Our findings suggest that the immunoregulatory T cell circuits in MCTD may be adequate both in postthymic precursor cells and in the thymic factor prompting. They are probably abnormal either at the site of Tmu signaling to Tar cells in feedback inhibition or in the Tmu reception of suppressor signals from Tgamma cells. The decrease of Tgamma cells in MCTD could be due to the decreased stimulus from feedback inhibition and/or to the penetration of anti-ribonucleoprotein antibody. Abnormalities of immunoregulatory T cell circuits in MCTD are quite different from those found previously in systemic lupus erythematosus, scleroderma, and rheumatoid arthritis. These differences support the notion that MCTD is a distinct entity.

We studied T cell surface markers, concanavalin A-induced, and spontaneously expanded suppressor cell function and the functions of postthymic precursor (Tar) cells in 3 patients with diphenylhydantoin (DPH)-related systemic lupus erythematosus (SLE). The findings were compared with those in 6 patients with spontaneously occurring SLE, 3 with active and 3 with inactive disease as well as with those in 3 normal volunteers. All 4 groups were age and sex matched. Findings were also compared to studies made in a group of 32 untreated idiopathic SLE patients and 32 normal controls. All T cell markers and immunoregulatory functions were normal in the DPH-treated SLE patients whereas all groups of patients with spontaneously occurring SLE had low numbers of t gamma cells, and Tar cells, and decreased concanavalin-A and spontaneously expended suppressor, human feedback inhibition and generation of suppression functions. Since consanguineous relatives of patients with spontaneously occurring SLE have been shown to have decreased suppressor cell function and patients with long-inactive spontaneous SLE continue to have defects in their T cell circuits, our findings may indicate that, in patients who develop SLE upon DPH intake the lupus diathesis uncovered by the drug probably resides in a site of immunoregulation different from that involved in spontaneously occurring lupus.