Omalizumab for the Treatment of Multiple Food Allergies.

BACKGROUND: Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy. METHODS: In this trial, we assessed whether omalizumab, a monoclonal anti-IgE antibody, would be effective and safe as monotherapy in patients with multiple food allergies. Persons 1 to 55 years of age who were allergic to peanuts and at least two other trial-specified foods (cashew, milk, egg, walnut, wheat, and hazelnut) were screened. Inclusion required a reaction to a food challenge of 100 mg or less of peanut protein and 300 mg or less of the two other foods. Participants were randomly assigned, in a 2:1 ratio, to receive omalizumab or placebo administered subcutaneously (with the dose based on weight and IgE levels) every 2 to 4 weeks for 16 to 20 weeks, after which the challenges were repeated. The primary end point was ingestion of peanut protein in a single dose of 600 mg or more without dose-limiting symptoms. The three key secondary end points were the consumption of cashew, of milk, and of egg in single doses of at least 1000 mg each without dose-limiting symptoms. The first 60 participants (59 of whom were children or adolescents) who completed this first stage were enrolled in a 24-week open-label extension. RESULTS: Of the 462 persons who were screened, 180 underwent randomization. The analysis population consisted of the 177 children and adolescents (1 to 17 years of age). A total of 79 of the 118 participants (67%) receiving omalizumab met the primary end-point criteria, as compared with 4 of the 59 participants (7%) receiving placebo (P<0.001). Results for the key secondary end points were consistent with those of the primary end point (cashew, 41% vs. 3%; milk, 66% vs. 10%; egg, 67% vs. 0%; P<0.001 for all comparisons). Safety end points did not differ between the groups, aside from more injection-site reactions in the omalizumab group. CONCLUSIONS: In persons as young as 1 year of age with multiple food allergies, omalizumab treatment for 16 weeks was superior to placebo in increasing the reaction threshold for peanut and other common food allergens. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT03881696.).

Evaluation and comparison of aging education for undergraduates across multiple fields of study.

The college years represent a key opportunity for broadening the future gerontology workforce by introducing students to the aging content that may influence their career decisions, yet this content is often limited to students with behavioral health and health professions majors. The present study sought to determine the degree to which a Midwestern university's general education course on aging could increase learning, interest, knowledge, and ability to use knowledge for undergraduates across multiple fields of study. Participants included 560 undergraduate students, 48% of which were health professions majors, 28% behavioral health majors, and 23% majors in other fields. While all groups reported significant increases in learning, knowledge, and interest in aging studies, ANOVA found significant differences by students' field of study in reported ability to apply course knowledge in their career or organization. As demand increases for workers versed in the needs of the older adult population, it will be important for educators to incorporate career connections into aging studies coursework and make abundantly clear how students in all fields of study are necessary for the future gerontological workforce.

Cancer History Avoids the Increase of Senescence Markers in Peripheral Cells of Amnestic Mild Cognitive Impaired Patients.

Epidemiological studies show that having a history of cancer protects from the development of Alzheimer's Disease (AD), and vice versa, AD protects from cancer. The mechanism of this mutual protection is unknown. We have reported that the peripheral blood mononuclear cells (PBMC) of amnestic cognitive impairment (aMCI) and Alzheimer's Disease (AD) patients have increased susceptibility to oxidative cell death compared to control subjects, and from the opposite standpoint a cancer history is associated with increased resistance to oxidative stress cell death in PBMCs, even in those subjects who have cancer history and aMCI (Ca + aMCI). Cellular senescence is a regulator of susceptibility to cell death and has been related to the pathophysiology of AD and cancer. Recently, we showed that cellular senescence markers can be tracked in PBMCs of aMCI patients, so we here investigated whether these senescence markers are dependent on having a history of cancer. Senescence-associated ßeta-galactosidase (SA-ß-Gal) activity, G0-G1 phase cell-cycle arrest, p16 and p53 were analyzed by flow cytometry; phosphorylated H2A histone family member X (γH2AX) by immunofluorescence; IL-6 and IL-8 mRNA by qPCR; and plasmatic levels by ELISA. Senescence markers that were elevated in PBMCs of aMCI patients, such as SA-ß-Gal, Go-G1 arrested cells, IL-6 and IL-8 mRNA expression, and IL-8 plasmatic levels, were decreased in PBMCs of Ca + aMCI patients to levels similar to those of controls or of cancer survivors without cognitive impairment, suggesting that cancer in the past leaves a fingerprint that can be peripherally traceable in PBMC samples. These results support the hypothesis that the senescence process might be involved in the inverse association between cancer and AD.

The impact of a two-year long COVID-19 public health restriction program on mechanical thrombectomy outcomes in a stroke network.

OBJECTIVE: The purpose of this study was to evaluate the impact of COVID-19 pandemic public health restrictions on our drip and ship mechanical thrombectomy program in Santiago Chile. MATERIALS AND METHODS: This was a retrospective analysis of a prospectively collected database comparing two cohorts, one during a two-year period before COVID-19 and the second during the two years of the pandemic at our metropolitan stroke program. RESULTS: A total of 100 patients were included in the pre COVID-19 cohort (cohort 1) and 121 in the COVID-19 cohort (cohort 2). There was a significant difference between cohorts, with older patients, different occlusion sites and higher door to arterial puncture time during the COVID-19 period. A non-significant trend for worse 90-day outcomes and higher mortality was present in cohort 2. There were no statistical differences in safety treatment parameters. CONCLUSIONS: COVID-19 pandemic has had a measurable impact on our mechanical thrombectomy program. Results showed similarities to other reported Latin American series, where less robust health systems could adapt less efficiently compared to developed countries. After two years of public health restrictions, there were changes in the treatment population characteristics, delay in some internal management metrics and a non-significant trend to worse 90-day outcomes and higher mortality.

Interferon Gamma Secretion of Adaptive and Innate Immune Cells as a Parameter to Describe Leukaemia-Derived Dendritic-Cell-Mediated Immune Responses in Acute Myeloid Leukaemia in vitro.

INTRODUCTION: Myeloid leukaemic blasts can be converted into leukaemia-derived dendritic cells (DCleu), characterised by the simultaneous expression of dendritic- and leukaemia-associated antigens, which have the competence to prime and enhance (leukaemia-specific) immune responses with the whole leukaemic antigen repertoire. To display and further specify dendritic cell (DC)- and DCleu-mediated immune responses, we analysed the interferon gamma (IFNy) secretion of innate and adaptive immune cells. METHODS: DC/DCleu were generated from leukaemic whole blood (WB) with (blast)modulatory Kit-I (granulocyte-macrophage colony-stimulating factor [GM-CSF] + Picibanil [OK-432]) and Kit-M (GM-CSF + prostaglandin E1) and were used to stimulate T cell-enriched immunoreactive cells. Initiated anti-leukaemic cytotoxicity was investigated with a cytotoxicity fluorolysis assay. Initiated IFNy secretion of T, NK, CIK, and iNKT cells was investigated with a cytokine secretion assay (CSA). IFNy positivity was additionally evaluated with an intracellular cytokine assay (ICA). Recent activation of leukaemia-specific cells was verified through addition of leukaemia-associated antigens (LAA; WT-1 and Prame). RESULTS: We found Kit-I and Kit-M competent to generate mature DC and DCleu from leukaemic WB without induction of blast proliferation. Stimulation of immunoreactive cells with DC/DCleu regularly resulted in an increased anti-leukaemic cytotoxicity and increased IFNy secretion of T, NK, and CIK cells, pointing to the significant role of DC/DCleu in leukaemia-specific alongside anti-leukaemic reactions. Interestingly, an addition of LAA did not further increase IFNy secretion, suggesting an efficient activation of leukaemia-specific cells. Here, both the CSA and ICA yielded comparable frequencies of IFNy-positive cells. Remarkably, the anti-leukaemic cytotoxicity positively correlated with the IFNy secretion in TCD3+, TCD4+, TCD8+, and NKCD56+ cells. CONCLUSION: Ultimately, the IFNy secretion of innate and adaptive immune cells appeared to be a suitable parameter to assess and monitor the efficacy of in vitro and potentially in vivo acute myeloid leukaemia immunotherapy. The CSA in this regard proved to be a convenient and reproducible technique to detect and phenotypically characterise IFNy-secreting cells. In respect to our studies on DC-based immunomodulation, we were able to display the potential of DC/DCleu to induce or improve leukaemia-specific and anti-leukaemic activity.

Senescence Markers in Peripheral Blood Mononuclear Cells in Amnestic Mild Cognitive Impairment and Alzheimer's Disease.

Recent studies suggest that cellular senescence plays a role in Alzheimer's Disease (AD) pathogenesis. We hypothesize that cellular senescence markers might be tracked in the peripheral tissues of AD patients. Senescence hallmarks, including altered metabolism, cell-cycle arrest, DNA damage response (DDR) and senescence secretory associated phenotype (SASP), were measured in peripheral blood mononuclear cells (PBMCs) of healthy controls (HC), amnestic mild cognitive impairment (aMCI) and AD patients. Senescence-associated ßeta-galactosidase (SA-ß-Gal) activity, G0-G1 phase cell-cycle arrest, p16 and p53 were analyzed by flow cytometry, while IL-6 and IL-8 mRNA were analyzed by qPCR, and phosphorylated H2A histone family member X (γH2AX) was analyzed by immunofluorescence. Senescent cells in the brain tissue were determined with lipofuscin staining. An increase in the number of senescent cells was observed in the frontal cortex and hippocampus of advanced AD patients. PBMCs of aMCI patients, but not in AD, showed increased SA-ß-Gal compared with HCs. aMCI PBMCs also had increased IL-6 and IL8 mRNA expression and number of cells arrested at G0-G1, which were absent in AD. Instead, AD PBMCs had significantly increased p16 and p53 expression and decreased γH2Ax activity compared with HC. This study reports that several markers of cellular senescence can be measured in PBMCs of aMCI and AD patients.

The ReFRAME library as a comprehensive drug repurposing library and its application to the treatment of cryptosporidiosis.

The chemical diversity and known safety profiles of drugs previously tested in humans make them a valuable set of compounds to explore potential therapeutic utility in indications outside those originally targeted, especially neglected tropical diseases. This practice of "drug repurposing" has become commonplace in academic and other nonprofit drug-discovery efforts, with the appeal that significantly less time and resources are required to advance a candidate into the clinic. Here, we report a comprehensive open-access, drug repositioning screening set of 12,000 compounds (termed ReFRAME; Repurposing, Focused Rescue, and Accelerated Medchem) that was assembled by combining three widely used commercial drug competitive intelligence databases (Clarivate Integrity, GVK Excelra GoStar, and Citeline Pharmaprojects), together with extensive patent mining of small molecules that have been dosed in humans. To date, 12,000 compounds (∼80% of compounds identified from data mining) have been purchased or synthesized and subsequently plated for screening. To exemplify its utility, this collection was screened against Cryptosporidium spp., a major cause of childhood diarrhea in the developing world, and two active compounds previously tested in humans for other therapeutic indications were identified. Both compounds, VB-201 and a structurally related analog of ASP-7962, were subsequently shown to be efficacious in animal models of Cryptosporidium infection at clinically relevant doses, based on available human doses. In addition, an open-access data portal (https://reframedb.org) has been developed to share ReFRAME screen hits to encourage additional follow-up and maximize the impact of the ReFRAME screening collection.

High School Day Camp Provides Insight into the Career Path and Recruitment of Future Physicians.

A physician shortage is predicted within the next 10 years in the U.S. Multiple obstacles may prevent students from choosing a career as a medical doctor including understanding of the career path. Minimizing this shortage and improving physician recruitment are being pursued. One endeavor is to address medical careers for students at the high school level. A one-day camp for high school students with an interest in a career as a physician was designed to minimize these obstacles and improve understanding of the physician career path. The camp comprised morning informational sessions with panels of undergraduate students, medical students, residents, and attending physicians. The afternoon session included hands-on activities related to physician training. Pre-camp and post-camp surveys were administered to obtain demographic information, interest level in practicing medicine, impact of the camp on understanding of career path, and the camp's influence on student comprehension of the daily routine for a physician. Results from the surveys show a significant benefit in increasing students' knowledge of the physician workday and the path to becoming a physician. Further considerations for this camp include establishing a mentorship program for high school students, reaching out to underrepresented groups in healthcare, and encouraging participation from rural areas. The camp was established through the Sioux Falls, South Dakota, local Women in Medicine and Sciences (WIMS) chapter. It is now an annual event, continuing to benefit South Dakota high school students with interests in medicine.

PGE1-Containing Protocols Generate Mature (Leukemia-Derived) Dendritic Cells Directly from Leukemic Whole Blood.

Dendritic cells (DCs) and leukemia-derived DC (DCleu) are potent stimulators of various immunoreactive cells and they play a pivotal role in the (re-) activation of the immune system. As a potential treatment tool for patients with acute myeloid leukemia, we developed and analyzed two new PGE1-containing protocols (Pici-PGE1, Kit M) to generate DC/DCleu ex vivo from leukemic peripheral blood mononuclear cells (PBMCs) or directly from leukemic whole blood (WB) to simulate physiological conditions. Pici-PGE1 generated significantly higher amounts of DCs from leukemic and healthy PBMCs when compared to control and comparable amounts as the already established protocol Pici-PGE2. The proportions of sufficient DC-generation were even higher after DC/DCleu-generation with Pici-PGE1. With Kits, it was possible to generate DCs and DCleu directly from leukemic and healthy WB without induction of blast proliferation. The average amounts of generated DCs and DCleu-subgroups were comparable with all Kits. The PGE1 containing Kit M generated significantly higher amounts of mature DCs when compared to the PGE2-containing Kit K and increased the anti-leukemic-activity. In summary PGE1-containing protocols were suitable for generating DC/DCleu from PBMCs as well as from WB, which reliably (re-) activated immunoreactive cells, improved the overall ex vivo anti-leukemic activity, and influenced cytokine-release-profiles.

Human Rhinovirus Diversity and Evolution: How Strange the Change from Major to Minor.

Rhinoviruses are the most common causes of the common cold. Their many distinct lineages fall into "major" and "minor" groups that use different cell surface receptors to enter host cells. Minor-group rhinoviruses are more immunogenic in laboratory studies, although their patterns of transmission and their cold symptoms are broadly similar to those of the major group. Here we present evolutionary evidence that minor-group viruses are also more immunogenic in humans. A key finding is that rates of amino acid substitutions at exposed sites in the capsid proteins VP2, VP3, and VP1 tend to be elevated in minor-group relative to major-group viruses, while rates at buried sites show no consistent differences. A reanalysis of historical virus watch data also indicates a higher immunogenicity of minor-group viruses, consistent with our findings about evolutionary rates at amino acid positions most directly exposed to immune surveillance. The increased immunogenicity and speed of evolution in minor-group lineages may contribute to the very large numbers of rhinovirus serotypes that coexist while differing in virulence.IMPORTANCE Most colds are caused by rhinoviruses (RVs). Those caused by a subset known as the minor-group members of rhinovirus species A (RV-A) are correlated with the inception and aggravation of asthma in at-risk populations. Genetically, minor-group viruses are similar to major-group RV-A, from which they were derived, although they tend to elicit stronger immune responses. Differences in their rates and patterns of molecular evolution should be highly relevant to their epidemiology. All RV-A strains show high rates of amino acid substitutions in the capsid proteins at exposed sites not previously identified as being immunogenic, and this increase is significantly greater in minor-group viruses. These findings will inform future studies of the recently discovered RV-C, which also appears to exacerbate asthma in adults and children. In addition, these findings draw attention to the difficult problem of explaining the long-term coexistence of many serotypes of major- and minor-group RVs.

[Neisseria meningitidis pneumonia. A case report]. / Neumonía bacterémica por Neisseria meningitidis: Primer caso reportado en Chile y revisión bibliográfica.

Few cases of bacteremic pneumonia by Neisseria meningitidis (NM) have been described worldwide; mostly in elderly patients or those with comorbidities. They appear clinically indistinguishable from other acute infectious pneumoniae, that do not develope the syndrome of meningococcemia. We report a 17-years-old male, without prior medical history, consulting in the emergency department with a 7-day history of productive cough, right pleural pain, fever and dyspnea. He was admitted to the ICU due to septic shock and respiratory distress. He was managed with vasoactive drugs and prone positioning ventilation for 48 hours. Chest radiography showed a right superior lobe condensation. The electrocardiogram and echocardiogram suggested septic myocarditis. Blood cultures demonstrated the presence of serogroup W135-NM. A lumbar puncture ruled out meningitis, and a 10-day ceftriaxone therapy was completed favorably.

Hair Transplantation Controversies.

BACKGROUND: Hair transplant surgery creates consistently natural appearing transplanted hair for men. It is increasingly popular procedure to restore natural growing hair for men with hair loss. OBJECTIVE: To review some current controversies in hair transplant surgery. MATERIALS AND METHODS: Review of the English PubMed literature and specialty literature in hair transplant surgery. RESULTS: Some of the controversies in hair transplant surgery include appropriate donor harvesting technique including elliptical donor harvesting versus follicular unit extraction whether manual versus robotic, the role of platelet-rich plasma and low-level light surgery in hair transplant surgery. CONCLUSION: Hair transplant surgery creates consistently natural appearing hair. As with all techniques, there are controversies regarding the optimal method for performing the procedure. Some of the current controversies in hair transplant surgery include optimal donor harvesting techniques, elliptical donor harvesting versus follicular unit extraction, the role of low-level light therapy and the platelet-rich plasma therapy in the procedure. Future studies will further clarify their role in the procedure.

A Novel Multi-Targeting Approach to Treating Hair Loss, Using Standardized Nutraceuticals.

Hair loss is a complicated problem that causes significant concern for those who are affected. Patients seeking medical treatment have limited options that include topical minoxidil and oral finasteride. While these treatments are backed by long term clinical use and research outcomes, many patients find topical minoxidil difficult to incorporate into their daily routine and some are concerned with the side effects associated with finasteride. In the office setting, patients may be treated with more invasive procedures such as platelet-rich plasma injections (PRP) and hair transplantation, treatments that often must be repeated and can lead to a costly investment. Consumers are increasingly interested in natural treatments for hair loss. Many turn to basic supplements only to be disappointed when they fail to deliver due to lack of standardization and efficacy. In this paper we review the benefits of a nutraceutical containing a specific blend of highly purified, standardized, bio-optimized, and bioavailable botanical extracts to treat hair loss. These phytoactives were selected because of their diverse multi-modal biologic activity against inflammation, DHT, stress mediators, oxidative damage, and intermediary signaling cascades. This supplement represents a paradigm shift as it addresses not only the factors that trigger hair loss but the downstream mediators of inflammation as well. Multi-center clinical studies are currently underway to confirm the efficacy and benefits of this unique nutraceutical.

J Drugs Dermatol. 2017;16(11 Suppl):s141-148.

Hair transplantation update.

Contemporary hair transplant surgery offers results that are natural and undetectable. It is an excellent treatment option for male and female pattern hair loss. Patients are encouraged to also use medical therapy to help protect their surgical results and prevent ongoing thinning of the surrounding hairs. The two major techniques of donor elliptical harvesting and follicular unit extraction are discussed here.

Usability testing of a fall prevention toolkit.

OBJECTIVES: This study sought to evaluate a fall prevention toolkit, determine its ease of use and user satisfaction, and determine the preferred venue of distribution. METHODS: Three forms of assessment were used: focus groups, usability testing, and surveys. Focus group participants were recruited from four locations: two rural health clinics and two urban centers. Usability testing participants were recruited from two rural health clinics. Survey questions included self-reported prior falls, current fall prevention habits, reaction to the toolkit, and demographics. RESULTS: Participants reported the toolkit was attractive, well-organized, and easy to use, but may contain too much information. Most participants admitted they would not actively use the toolkit on their own, but prefer having it introduced by a healthcare provider or in a social setting. CONCLUSIONS: Healthcare focuses on customer satisfaction; therefore, providers benefit from knowing patient preferred methods of learning fall prevention strategies.

Passive and active exercises are similarly effective in elderly nursing home residents.

[Purpose] The aim of this study was to compare the efficacy of passive motion exercise and active motion exercise on functional fitness in elderly nursing home residents. [Subjects and Methods] Twenty-three (female 22 and male 1) nursing home residents (84.8±4.3 yr) volunteered for this study. They were divided into a passive motion exercise group (n=12) and an active motion exercise group (n=11) and performed 30-min sessions of training twice a week for 12 weeks. Functional fitness (Arm Curl, Chair Stand, Up & Go, Sit & Reach, Back Scratch, functional Reach, and 12-min Walk tests) was evaluated before and after the intervention. [Results] No significant baseline difference was noted between the groups in measured variables. Following the 12 week intervention, no significant interaction (group × time) was noted in functional fitness variables between the groups, except for the functional reach scores (active motion exercise 40%, passive motion exercise 9%). Significant improvement over time was noted in passive motion exercise group in Arm Curl (19%), Chair Stand (15%), Up & Go (6%), and 12-min Walk (12%) scores; and in the active motion exercise group in Arm Curl (14%), Chair Stand (19%), Up & Go (11%), functional Reach (40%) and 12-min Walk (13%) scores. The adherence rates in the passive and active motion exercise groups were 95.8% and 93.1% respectively. [Conclusion] Passive motion exercise and active motion exercise were found to be similarly effective for improving the functional fitness of elderly nursing home residents.

Anal Pap smears and anal cancer: what dermatologists should know.

Squamous epithelial cells are susceptible to infection by the human papillomavirus. Infection of squamous epithelium with oncogenic human papillomavirus types is associated with development of dysplasia and potential malignant transformation. Historically, cervical cancer has been the most prevalent human papillomavirus-induced squamous neoplasia. However, because of widespread screening via Pap smear testing, rates of cervical cancer in the United States have decreased dramatically during the past 50 years. Rates of anal cancer, in contrast, have doubled during the past 30 years. The groups at highest risk for development of anal cancer are men who have sex with men, HIV-positive patients, and patients immunosuppressed as a result of solid-organ transplantation. By detecting dysplasia before it develops into invasive cancer, anal Pap smears may be a potentially useful screening tool for anal cancer, particularly in individuals known to be at increased risk. However, at this time, sufficient data supporting the benefit of anal Pap smear screening are lacking. With insufficient evidence, no national health care organizations currently recommend the use of anal Pap smears as a routine screening test, even among high-risk groups.

Low-income urban Latino parents' perceptions of immunization text reminders.

OBJECTIVE: Identify perceptions regarding benefits of and barriers to receiving text messages for immunization reminders and preferred content for such text messages. DESIGN: Structured interviews. SETTING: Outpatient pediatric resident and faculty clinic. PARTICIPANTS: A convenience sample of 54 low-income urban Latino parents of children aged < or = 2 years. MAIN OUTCOME MEASURES: Parent perspectives on text message reminders. RESULTS: Most respondents were female (70%), married (63%), and fluent only in Spanish (89%). Most (83%) had a health literacy score in the adequate range. All (100%) reported being interested in receiving immunization reminders by text message, and 81% reported being willing to receive general appointment reminders by text message. Parents made 72 comments regarding benefits of text message immunization reminders. The most common sub-category was usefulness of the reminders (53%). These comments reflected participants' busy schedules and the beneficial nature of text messages in reminding parents of appointments. Fifty-six comments were provided regarding barriers to receiving text message reminders. Most comments (77%) indicated no identifiable barriers. Twenty percent described barriers related to technology, such as costs or lack of text messaging service. Parents generated 108 comments regarding preferred content of reminders. The topics most frequently identified were appointment date and time (32%), names of the vaccines (19%), and the child's name (11%). CONCLUSIONS: Low-income Latino parents perceive text message immunization reminders as a feasible alternative to more traditional forms of communication.