Boric acid crosslinked chitosan microcapsules loaded with frankincense oil for the development of mosquito-repellent, antibacterial, antioxidant, and flame-retardant cotton.

In ancient times, textiles were only used for covering the human body. Nowadays, people are looking for functional textiles to provide additional functional properties. In the present work, an attempt was made to develop chitosan and boric acid-based microcapsules loaded with frankincense oil. Application of these microcapsules was done on cotton using a pad-dry method. The release rate, encapsulation efficiency and microencapsulation yield of microcapsules, and functional properties of finished fabric were studied. The prepared microcapsules were also characterised by different techniques like SEM, FTIR, TGA, and EDX. The finished fabric exhibited mosquito repellency (100 %), antioxidant activity (>66 %), antibacterial activity against E. coli (88.69 %) and S. aureus (94.5 %), and LOI of 24 with a pleasant aroma.

The Risk of Allergic Reaction to SARS-CoV-2 Vaccines and Recommended Evaluation and Management: A Systematic Review, Meta-Analysis, GRADE Assessment, and International Consensus Approach.

Concerns for anaphylaxis may hamper severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization efforts. We convened a multidisciplinary group of international experts in anaphylaxis composed of allergy, infectious disease, emergency medicine, and front-line clinicians to systematically develop recommendations regarding SARS-CoV-2 vaccine immediate allergic reactions. Medline, EMBASE, Web of Science, the World Health Organizstion (WHO) global coronavirus database, and the gray literature (inception, March 19, 2021) were systematically searched. Paired reviewers independently selected studies addressing anaphylaxis after SARS-CoV-2 vaccination, polyethylene glycol (PEG) and polysorbate allergy, and accuracy of allergy testing for SARS-CoV-2 vaccine allergy. Random effects models synthesized the data to inform recommendations based on the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach, agreed upon using a modified Delphi panel. The incidence of SARS-CoV-2 vaccine anaphylaxis is 7.91 cases per million (n = 41,000,000 vaccinations; 95% confidence interval [95% CI] 4.02-15.59; 26 studies, moderate certainty), the incidence of 0.15 cases per million patient-years (95% CI 0.11-0.2), and the sensitivity for PEG skin testing is poor, although specificity is high (15 studies, very low certainty). We recommend vaccination over either no vaccination or performing SARS-CoV-2 vaccine/excipient screening allergy testing for individuals without history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient, and a shared decision-making paradigm in consultation with an allergy specialist for individuals with a history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient. We recommend further research to clarify SARS-CoV-2 vaccine/vaccine excipient testing utility in individuals potentially allergic to SARS-CoV2 vaccines or their excipients.

A 45-year-old man with elevated levels of immunoglobulin A.

Quantitative immunoglobulin tests are often ordered as part of the initial evaluation for suspected immune deficiency. Although alterations in immunoglobulin levels can explain recurrent infections, in a patient without symptoms, there are a variety of other factors that can alter immunoglobulin levels. Common causes for elevated immunoglobulin A levels include malignancy and hepatic impairment in addition to a variety of infiltrative, infectious, and inflammatory diseases. We present a case of a 45-year-old man with a history of recurrent sinopulmonary symptoms without bacterial infection found to have an isolated elevated level of immunoglobulin A.

Gastric-sparing nitric oxide-releasable 'true' prodrugs of aspirin and naproxen.

Nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) are gaining attention as potentially gastric-sparing NSAIDs. Herein, we report a novel class of '1-(nitrooxy)ethyl ester' group-containing NSAIDS as efficient NO releasing 'true' prodrugs of aspirin and naproxen. While an aspirin prodrug exhibited comparable oral bioavailability and antiplatelet activity (i.e., TXB2 inhibition) to those of aspirin, a naproxen prodrug exhibited better bioavailability than naproxen. These promising NO-NSAIDs protected experimental rats from gastric damage. We therefore believe that these promising NO-NSAIDs could represent a new class of potentially 'Safe NSAIDs' for the treatment of arthritic pain, inflammation and cardiovascular disorders in the case of NO-aspirin.

Angioedema deaths in the United States, 1979-2010.

BACKGROUND: Hospital admission data indicate that the angioedema incidence has increased during the past several decades. Little is known about mortality trends. OBJECTIVES: To count the number of deaths associated with angioedema in the United States, investigate correlations with age, sex, race, and other contributory causes, and analyze trends from 1979 to 2010. METHODS: All US death certificates in which angioedema was listed as an underlying or contributing cause of death during 1979 to 2010 were analyzed. Age-adjusted mortality rates were analyzed by age, sex, and race. Other conditions designated as the underlying cause of death were investigated. RESULTS: From 1979 to 2010, there were 5,758 deaths in which angioedema was listed as a contributing cause. The age-adjusted death rate for hereditary angioedema decreased from 0.28 (95% confidence interval [CI] 0.25-0.32) to 0.06 (95% CI 0.05-0.08) per million persons per year. Conversely, mortality for angioedema increased from 0.24 (95% CI 0.21-0.27) to 0.34 (95% CI 0.31-0.37) per million. Blacks constituted 55% of angioedema deaths that were associated with use of angiotensin-converting enzyme inhibitors. On death certificates that listed hereditary angioedema as the underlying cause of death, cancer (frequently lymphoma or leukemia) was the second most commonly listed cause. CONCLUSION: Angioedema-associated deaths were very rare from 1979 to 2010. Hereditary angioedema deaths became even more so, whereas nonhereditary angioedema deaths increased. Risks associated with angiotensin-converting enzyme inhibitors were higher in blacks. Lack of specific coding for acquired angioedema most likely explains the observed association between cancer and hereditary angioedema. In the future, more granular coding systems may help distinguish hereditary from acquired angioedema.

Detailed analysis of allergic cutaneous reactions to spinal cord stimulator devices.

The use of spinal cord stimulation (SCS) devices to treat chronic, refractory neuropathic pain continues to expand in application. While device-related complications have been well described, inflammatory reactions to the components of these devices remain underreported. In contrast, hypersensitivity reactions associated with other implanted therapies, such as endovascular and cardiac rhythm devices, have been detailed. The purpose of this case series is to describe the clinical presentation and course of inflammatory reactions as well as the histology of these reactions. All patients required removal of the entire device after developing inflammatory reactions over a time course of 1-3 months. Two patients developed a foreign body reaction in the lead insertion wound as well as at the implantable pulse generator site, with histology positive for giant cells. One patient developed an inflammatory dermatitis on the flank and abdomen that resolved with topical hydrocortisone. "In vivo" testing with a lead extension fragment placed in the buttock resulted in a negative reaction followed by successful reimplantation of an SCS device. Inflammatory reactions to SCS devices can manifest as contact dermatitis, granuloma formation, or foreign body reactions with giant cell formation. Tissue diagnosis is essential, and is helpful to differentiate an inflammatory reaction from infection. The role of skin patch testing for 96 hours may not be suited to detect inflammatory giant cell reactions that manifest several weeks post implantation.

Long-term safety of mepolizumab for the treatment of hypereosinophilic syndromes.

BACKGROUND: Hypereosinophilic syndromes (HESs) are chronic disorders that require long-term therapy to suppress eosinophilia and clinical manifestations. Corticosteroids are usually effective, yet many patients become corticosteroid refractory or develop corticosteroid toxicity. Mepolizumab, a humanized monoclonal anti-IL-5 antibody, showed corticosteroid-sparing effects in a double-blind, placebo-controlled study of FIP1L1/PDGFRA-negative, corticosteroid-responsive subjects with HESs. OBJECTIVE: We evaluated long-term safety and efficacy of mepolizumab (750 mg) in HES. METHODS: MHE100901 is an open-label extension study. The primary end point was the frequency of adverse events (AEs). Optimal dosing frequency, corticosteroid-sparing effect of mepolizumab, and development of antimepolizumab antibodies were also explored. RESULTS: Seventy-eight subjects received 1 to 66 mepolizumab infusions each (including mepolizumab infusions received in the placebo-controlled trial). Mean exposure was 251 weeks (range, 4-302 weeks). The most common dosing interval was 9 to 12 weeks. The incidence of AEs was 932 events per 100 subject-years in the first year, declining to 461 events per 100 subject-years after 48 months. Serious AEs, including 1 death, were reported by the investigator as possibly due to mepolizumab in 3 subjects. The median daily prednisone dose decreased from 20.0 to 0 mg in the first 24 weeks. The median average daily dose for all subjects over the course of the study was 1.8 mg. Sixty-two percent of subjects were prednisone free without other HES medications for ≥ 12 consecutive weeks. No neutralizing antibodies were detected. Twenty-four subjects withdrew before study completion for death (n = 4), lack of efficacy (n = 6), or other reasons. CONCLUSION: Mepolizumab was well tolerated and effective as a long-term corticosteroid-sparing agent in PDGFRA-negative HES.

Novel oxazine skeletons as potential antiplasmodial active ingredients: Synthesis, in vitro and in vivo biology of some oxazine entities produced via cyclization of novel chalcone intermediates.

A novel series of 6-(2-chloroquinolin-3-yl)-4-substituted-phenyl-6H-1,3-oxazin-2-amines were synthesized and evaluated for in vitro antimalarial efficacy against chloroquine sensitive (MRC-02) as well as chloroquine resistant (RKL9) strains of Plasmodium falciparum. The activity tested was at nanomolar concentration. ß-Hematin formation inhibition activity (BHIA(50)) of oxazines were determined and correlated with antimalarial activity. A reasonably good correlation (r = 0.49 and 0.51, respectively) was observed between antimalarial activity (IC(50)) and BHIA(50). This suggests that antimalarial mode of action of these compounds seems to be similar to that of chloroquine and involves the inhibition of hemozoin formation. Some of the compounds were showing better antimalarial activity than chloroquine against resistant strain of P. falciparum and were also found to be active in the in vivo experiment.

Current strategies in the management of hypereosinophilic syndrome, including mepolizumab.

BACKGROUND: Patients with hypereosinophilic syndrome (HES) vary considerably in their clinical presentation with regard to the severity and pattern of end-organ involvement. Clinical manifestations range from nonspecific symptoms to life-threatening, multisystem damage caused by eosinophil infiltration and local release of proinflammatory mediators and toxic granule products from these invading cells. The primary objective of treatment is to reduce blood and tissue eosinophilia and prevent eosinophil-mediated tissue damage as safely as possible. Systemic corticosteroids, such as prednisone, are first-line therapy for the management of patients with symptomatic HES who lack the Fip1-like 1-platelet-derived growth factor receptor-alpha (FIP1L1-PDGFRA) gene fusion mutation. The tyrosine kinase inhibitor, imatinib, is first-line treatment for FIP1L1-PDGFRA-positive patients). Because of the toxicity and serious side-effects that can occur with oral corticosteroids, alternative therapies may need to be introduced to reduce the cumulative corticosteroid exposure while maintaining disease control. SCOPE: Among corticosteroid-sparing agents are cytotoxic drugs and interferon-alpha; anti-interleukin-5 (IL-5) monoclonal antibodies are also currently under investigation for the treatment of HES. This manuscript reviews the available treatments for HES and the range of side-effects associated with long-term corticosteroid use, and then focuses on the anti-IL-5 monoclonal antibodies, mepolizumab and reslizumab. Of these, only mepolizumab has been studied in a randomized, placebo-controlled trial. Literature search methodology utilized www.pubmed.gov and www.clinicaltrials.gov with search terms including hypereosinophilic syndrome and corticosteroid side-effects coupled with search terms including eosinophils, mepolizumab and reslizumab through March 2010. FINDINGS: Three case studies are presented that demonstrate the limitations of corticosteroid therapy in terms of tolerability and quality of life, and the subsequent use of mepolizumab as a corticosteroid-sparing agent in these individuals. CONCLUSION: Targeted eosinophil-directed therapy with an anti-IL-5 neutralizing monoclonal antibody reduced the need for corticosteroids in these three HES patients without disease exacerbations.

Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy.

BACKGROUND: Hypereosinophilic syndrome (HES) is a heterogeneous group of rare disorders defined by persistent blood eosinophilia > or =1.5 x 10(9)/L, absence of a secondary cause, and evidence of eosinophil-associated pathology. With the exception of a recent multicenter trial of mepolizumab (anti-IL-5 mAb), published therapeutic experience has been restricted to case reports and small case series. OBJECTIVE: The purpose of the study was to collect and summarize baseline demographic, clinical, and laboratory characteristics in a large, diverse cohort of patients with HES and to review responses to treatment with conventional and novel therapies. METHODS: Clinical and laboratory data from 188 patients with HES, seen between January 2001 and December 2006 at 11 institutions in the United States and Europe, were collected retrospectively by chart review. RESULTS: Eighteen of 161 patients (11%) tested were Fip1-like 1-platelet-derived growth factor receptor alpha (FIP1L1-PDGFRA) mutation-positive, and 29 of 168 patients tested (17%) had a demonstrable aberrant or clonal T-cell population. Corticosteroid monotherapy induced complete or partial responses at 1 month in 85% (120/141) of patients with most remaining on maintenance doses (median, 10 mg prednisone equivalent daily for 2 months to 20 years). Hydroxyurea and IFN-alpha (used in 64 and 46 patients, respectively) were also effective, but their use was limited by toxicity. Imatinib (used in 68 patients) was more effective in patients with the FIP1L1-PDGFRA mutation (88%) than in those without (23%; P < .001). CONCLUSION: This study, the largest clinical analysis of patients with HES to date, not only provides useful information for clinicians but also should stimulate prospective trials to optimize treatment of HES.

Advances in diagnosis and treatment of eosinophilia.

PURPOSE OF REVIEW: Hypereosinophilic syndromes (HESs) are disorders characterized by sustained blood or tissue hypereosinophilia or both with subsequent damage to various organs due to eosinophilic infiltration and release of mediators. HES are now recognized to include varied eosinophilic disorders for some of which there are recent insights into their pathogenesis and targeted treatment. RECENT FINDINGS: Studies have helped delineate two subtypes of HES: the myeloproliferative variants of HES and the lymphocytic variants of HES. Many, but not all, myeloproliferative-HES patients have interstitial deletions on chromosome 4q12 that lead to fusion of the FIP1-like 1 and platelet-derived growth factor receptor alpha genes, with the fusion product encoding a protein that has constitutive tyrosine kinase activity. Lymphocytic-HES is a primary lymphoid disorder characterized by nonmalignant expansion of a T-cell population able to produce eosinophilopoietic cytokines, with the T-cell population being identified by flow cytometry or reverse transcriptase-PCR for T-cell receptor usage or both. Other HES subtypes are of uncertain causes and are included in recent diagnostic algorithms for the spectrum of HES. SUMMARY: The contemporary definition of the hypereosinophilic syndromes encompasses a range of eosinophilic disorders characterized by chronic blood hypereosinophilia often with eosinophil-mediated damage to various organs.

Clinical overview of hypereosinophilic syndromes.

Hypereosinophilic syndrome (HES) or syndromes are disorders characterized by chronic peripheral blood hypereosinophilia with damage to various organs due toeosinophilic infiltration and release of mediators. HES is most accurately described as a collection of heterogeneous disorders, with some similarities in clinical features, but many differences. Based on recent advances in molecular and genetic diagnostic techniques and increasing experience with differences in clinical features and prognosis, some subtypes of HES have been defined, such as myeloproliferative variants, including chronic eosinophilic leukemia, and lymphocytic variants, but other subtypes remain undefined. Recent evidence suggests that, in addition to differences in clinical features, the range of complications, treatment options, and prognoses differs significantly among the myeloproliferative, lymphocytic, and undefined variants of HES.

A case of fever, eosinophilia, and pneumonia.

There is a broad differential for patients presenting with fever, eosinophilia, and pneumonia. We present a case of a 48-year-old man who presented with recurrent fever, pleuritic chest pain, and cough. His medical history was significant for a recent trip to Arizona. A chest X ray showed a right lower lobe infiltrate and CT examination of the chest showed extensive mediastinal lymphadenopathy. Tissue culture from a biopsy specimen of the mediastinal lymph nodes revealed growth of Coccidioides immitis and a diagnosis of coccidioidomycosis was made. He was treated with a total of a 9-month course of itraconazole and has remained disease free for >2 years. This case shows how a careful history and evaluation will direct the clinician to the correct diagnosis.