Is a search for game changers preventing us from focusing on the necessary tasks of systems strengthening and norm change to facilitate adolescent contraceptive use?

With a keen awareness of the size and health needs of the global adolescent population, governments, nongovernment organizations and the technical and funding agencies that support them continue to seek innovative answers to persistent programming challenges to increasing contraceptive use among sexually active adolescents. Adolescents 360 (A360) is a project implemented by Population Services International (PSI) and partners with funding from the Bill and Melinda Gates Foundation (BMGF) and the Children's Investment Fund Foundation (CIFF). The first phase of the project was implemented from 2016 - 2020 in Ethiopia, Nigeria, and Tanzania. A360 hypothesized that human centered design (HCD) could catalyze new insights into identifying and solving problems that limit adolescents' use of contraception. Despite initial promising results, A360 demonstrated very limited impact on modern contraceptive uptake among adolescents. The authors of this commentary were members of a technical advisory group to A360 and are uniquely positioned to provide insights on this project to complement those of A360's staff and evaluators, which are already in the public arena. Our analysis suggests that all stakeholders should take steps to rebalance their programs and investments to not only seek new solutions (i.e. game changers), but to also invest in the institutionalization of the solutions that have been generated over the past 40 years, prioritizing those that have shown evidence of effectiveness (i.e. adolescent responsive health service delivery) and those that demonstrate significant promise (i.e. social norm change).

The potential roles of strigolactones and brassinosteroids in the autoregulation of nodulation pathway.

BACKGROUND AND AIMS: The number of nodules formed on a legume root system is under the strict genetic control of the autoregulation of nodulation (AON) pathway. Plant hormones are thought to play a role in AON; however, the involvement of two hormones recently described as having a largely positive role in nodulation, strigolactones and brassinosteroids, has not been examined in the AON process. METHODS: A genetic approach was used to examine if strigolactones or brassinosteroids interact with the AON system in pea (Pisum sativum). Double mutants between shoot-acting (Psclv2, Psnark) and root-acting (Psrdn1) mutants of the AON pathway and strigolactone-deficient (Psccd8) or brassinosteroid-deficient (lk) mutants were generated and assessed for various aspects of nodulation. Strigolactone production by AON mutant roots was also investigated. KEY RESULTS: Supernodulation of the roots was observed in both brassinosteroid- and strigolactone-deficient AON double-mutant plants. This is despite the fact that the shoots of these plants displayed classic strigolactone-deficient (increased shoot branching) or brassinosteroid-deficient (extreme dwarf) phenotypes. No consistent effect of disruption of the AON pathway on strigolactone production was found, but root-acting Psrdn1 mutants did produce significantly more strigolactones. CONCLUSIONS: No evidence was found that strigolactones or brassinosteroids act downstream of the AON genes examined. While in pea the AON mutants are epistatic to brassinosteroid and strigolactone synthesis genes, we argue that these hormones are likely to act independently of the AON system, having a role in the promotion of nodule formation.

SCUAD and chronic rhinosinusitis. Reinforcing hypothesis driven research in difficult cases.

BACKGROUND: Our objective is to present recent research findings on recalcitrant chronic rhinosinusitis (CRS) in relation to "Severe Chronic Upper Airway Disease" (SCUAD). METHODOLOGY: Literature review using Medline and Em base databases (search terms 'chronic rhinosinusitis'; "chronic sinusitis" or"Severe Chronic Upper Airway Disease") limited to articles published in the English language. RESULTS: Complex pathophysiological mechanisms characterize various forms of chronic rhinitis and rhinosinusitis (CRS), where inflammation persists in spite of adequate medical treatment. In these cases, a multifactorial etiology often underlies the development of sino-nasal inflammation. The interaction between chronic upper and lower airway inflammation via neurogenic and systemic pathways may complicate the therapy of these patients, and lead to insufficient symptom control. CONCLUSION: The recently introduced definition of"Severe Chronic Upper Airway Disease" (SCUAD) increases awareness of those patients with persistent inflammation and symptoms despite guideline-driven pharmacologic treatment. The concept of SCUAD may prove helpful in directing research towards clarifying the definition, diagnosis and pathophysiology of rhinitis and rhinosinusitis,their limits and overlap. In this review, a hypothesis on SCUAD immunopathology is also presented.

Microbial and acute phase stimuli disrupt promyelocytic leukemia tumor suppressive nodes.

The promyelocytic leukaemia (PML) nuclear domain (PML-ND) is a nuclear sentinel for stress. Each PML-ND cradles a delicate scaffold of nucleoproteins, many of which can trigger the apoptotic death cascade if disrupted. Given their place in integrating stress and death, PML-NDs are obvious targets for excision from injury pathways by viruses and cancers. Viruses express proteins dedicated to silencing the PML-ND network and their failure can presage the suppression of viral replication. To understand how PML-NDs protect the cell from stress we must discover those damage pathways with which they connect. Such data will reveal the panoply of signal pathways lost in PML null cells and the extent to which infection and cancer can desensitise the cell to therapeutic intervention. A convenient and sensitive method with which to detect PML-ND stress induction is its biophysical reorganisation, as well defined dose responsive modifications of PML protein accompany damage recognition. The experiments that we present in this manuscript arose from an observation that lipid mediated transfection of plasmid DNA triggered a dramatic modification of PML-NDs that was identical to that seen following their recognition of DNA damage. In later experiments, we identified lipoprotein and IL-6 as potential mediators of this response. Collectively these data are the first to link an endotoxin component and IL-6 to the PML-ND compartment and, given the role of PML in cell fate, suggest increasing complexity at the interface of immunity and carcinogenesis.

Eosinophilic mucin rhinosinusitis: a distinct clinicopathological entity.

BACKGROUND: Allergic fungal sinusitis (AFS) was recognized in 1981. Since 1983, a form of sinusitis histologically similar to AFS except for the absence of fungal hyphae has also been noted. The designation "eosinophilic mucin rhinosinusitis (EMRS)" is proposed. Its relationship to AFS is controversial and problematic. OBJECTIVE: To determine whether distinctive clinical and immunological differences exist to differentiate the histological entity of EMRS from AFS. STUDY DESIGN: Literature review and comparison of cases of AFS (n = 418) to EMRS (n = 40) from the literature, as well as cases of AFS (n = 13) and EMRS (n = 29) accrued in the present study. RESULTS: A total of 431 AFS patients were compared with 69 EMRS patients. The mean age of patients with AFS was significantly younger than patients with EMRS (30.7 y compared with 48.0 y, respectively; P < .001). Male-to-female ratios were 1.03:1 and 1.26:1 for AFS and EMRS, respectively, and were not significantly different. Forty-one percent of patients with AFS were asthmatic compared with 93% of patients with EMRS (P < .0001). Thirteen percent of patients with AFS were aspirin sensitive compared with 54% of patients with EMRS (P < .0001). Polyp occurrence was almost 100% in both groups. Eighty-four percent of patients with AFS had allergic rhinitis (AR), while only 63% of patients with EMRS had AR (P = .004). Fifty-five percent of AFS patients had bilateral disease, in contrast to the 100% of EMRS patients with bilateral disease (P < .0001). Although average total immunoglobulin E (IgE) was elevated in both groups, it was significantly more elevated in AFS patients (range, 12-13,084 mg/ dL; mean, 1,941 mg/dL) compared with EMRS patients (range, 14-1,162 mg/dL; mean, 267 mg/dL; P < .001). Total immunoglobulin G (IgG) and IgG subclasses were seldom reported in the cases available from the literature of either AFS or EMRS. However, in the present series of EMRS, IgG1 deficiency occurred in 50% of evaluated patients (mean, 475 +/- 175 mg/dL; range, 250-869 mg/dL; normal, 422 to 1,200 mg/dL) but in no cases of AFS reported in the literature. CONCLUSIONS: Significant clinical and immunological differences exist to distinguish AFS from EMRS. It is postulated that AFS is an allergic response to fungi in predisposed individuals, while EMRS occurs because of a systemic dysregulation of immunological controls. Because EMRS is a systemic disease, unilateral disease is not seen. In contrast, AFS, an allergic response to fungi, may occur unilaterally or bilaterally depending on the antigenic stimulation. EMRS also has a significantly higher association with asthma, an increased incidence of aspirin sensitivity, and an increased incidence of IgG1 deficiency. Therapy with a systemic steroid, a potent and indiscriminant anti-inflammatory agent, is a useful adjunct in both disorders. Fungal immunotherapy following surgical extirpation of AFS is useful in preventing AFS recurrence. It is predicted that fungal immunotherapy and antifungal agents will be ineffective in patients with EMRS. It is important to differentiate these two similar histopathological entities in future trials assessing therapeutic efficacy. Inclusion of both entities in a study could obscure recognition of the true effectiveness of intervention, because of the possible variable response differences between the two entities. This study shows that significant clinical and immunological differences exist between EMRS and AFS. The future awaits an exploration of the pathophysiological basis of these differences.

Spontaneous CSF otorrhea from tegmen and posterior fossa defects.

Spontaneous cerebrospinal otorrhea (SCSFO) from tegmen or posterior fossa defects is uncommon. Twenty-nine cases have been detailed in the literature to date. We report an additional four cases from three patients. This group of 33 cases of SCSFO from tegmen or posterior fossa defects is characterized by certain clinical features. These patients are usually older adults (mean age 48 years, range 8 months to 80 years). Aural fullness with a serous appearing middle ear effusion, or clear otorrhea, often subsequent to tube myringotomy, are the usual initial symptoms. Meningitis was the initial manifestation in eight patients (24%), and ultimately occurred in an additional four patients (12%). The pathophysiologic basis for SCSFO from tegmen defects is discussed. Methods for diagnosing and treating CSF otorrhea from tegmen defects are reviewed.

Sex steroid receptor distribution in the human larynx and laryngeal carcinoma.

Previous reports of estrogen receptor (ER) and progesterone receptor (PgR) in the human larynx and laryngeal carcinoma have relied on ligand-binding techniques using cytosol from tissue homogenates. These methods obscure the contribution of different tissue components to total receptor content. Recently developed, highly specific monoclonal antibodies to human ER and PgR were able to discern the presence of ER and PgR at the cellular level in 12 specimens of normal laryngeal tissue and eight laryngeal squamous cell carcinomas. Localization of ER and PgR was observed in the nuclei of vocalis muscle. No evidence of ER or PgR was found in epithelial components of the normal larynges or in laryngeal carcinomas. These results extend previous findings in lower primates and rodents to the human larynx and clarify previously reported receptor analyses of laryngeal carcinomas.

Youth at the threshold of the 21st century: the demographic situation.

PIP: The author discusses the elements of social change in terms of natality, mortality, and adolescent health; the changing nature of the family; population aging; rapid urbanization; urban growth and economic opportunity; education and youth; and employment for youth. She concludes that the effects of economic development on health remain secondary to most other developmental concerns. Policymakers need to instead regard health as a key element which contributes to the quality of life and not just as a means by which other developmental objectives may be achieved. As current demographic conditions in the world fundamentally transform the cultural and social contexts in which young people develop, interventions should increasingly focus upon the predictors and conditions of adolescent development rather than upon the behaviors themselves.^ieng

A study of the effect of nasal steroid sprays in perennial allergic rhinitis patients with rhinitis medicamentosa.

OBJECTIVE: To determine if rebound congestion can be reduced with concomitant nasal steroid spray usage. STUDY DESIGN AND SETTING: Randomized, double blind, controlled single center study. PARTICIPANTS: Twenty subjects with perennial allergic rhinitis with nasal congestion. INTERVENTION: All subjects received 3 weeks of twice-daily oxymetazoline. After 2 weeks, subjects were randomized to 2 additional weeks of concomitant budesonide aqueous nasal spray (n = 9) or placebo (n = 10). In the sixth week, all sprays were stopped. RESULTS: Both groups showed subjective and objective evidence of rebound congestion 24 hours after cessation of oxymetazoline (P < 0.05). Subjective rebound congestion resolved in 48 hours in the budesonide aqueous nasal spray group but persisted for over 1 week in the placebo group. CONCLUSION: Rebound congestion is objectively present in patients with perennial allergic rhinitis after 3 weeks of oxymetazoline spray. Rebound congestion is reduced by concomitant budesonide aqueous nasal spray use. SIGNIFICANCE: This study supports the common clinical practice of nasal steroid sprays to ameliorate rebound congestion concomitant with and after cessation of topical decongestant sprays.

Allergic fungal sinusitis: allergic, infectious, or both?

Allergic fungal sinusitis is a benign noninvasive sinus disease related to a hypersensitivity reaction to fungal antigens. A wide variety of fungal agents has been implicated, with the vast majority belonging to the Dematiaceae family. Allergic fungal sinusitis should be suspected in any atopic patient with refractory nasal polyps. Sinus computed tomograms and magnetic resonance imaging findings can be quite distinctive, but not diagnostic. Diagnosis requires histopathologic examination, which shows characteristic allergic mucin. Hyphae can be demonstrated on special fungal stains or confirmed by a positive fungal culture. At surgery, the diagnosis should be considered if thick, tenacious allergic mucin is encountered in the atopic patient with nasal polyps. Fungal cultures should then be obtained, and the pathologist alerted to the possible diagnosis of allergic fungal sinusitis. Current recommendations for therapy include conservative but complete exenteration of all allergic mucin. This can often be accomplished endoscopically. Adjunctive short-term systemic steroids are often helpful, and nasal steroid sprays should be continued long term. The length and dose of steroid therapy is controversial. Persistence of allergic fungal sinusitis with recurrence of sinonasal symptoms is common, particularly when there has been incomplete eradication of allergic fungal mucin. Even when the patient is clinically disease free, recurrence can occur, presumably from reexposure to fungal antigens. Therefore close clinical, endoscopic, and radiographic follow-up is important.

Giant cell arteritis and polymyalgia rheumatica. Review for the otolaryngologist.

Patients suspected of giant cell arteritis or polymyalgia rheumatica are often referred to the otolaryngologist for temporal artery biopsy. These patients may initially present to the otolaryngologist with symptoms referable to the head and neck. A comprehensive review of these two interrelated disorders is provided, with emphasis on head and neck manifestations and features of obtaining the temporal artery biopsy specimen.

Hyperbaric oxygen therapy for laryngeal radionecrosis.

Radionecrosis of the larynx is a debilitating disease associated with pain, dysphagia, respiratory obstruction, and, in some cases, the need for laryngectomy. Persistent poor wound healing can lead to death. A series of eight patients with advanced (grades III and IV, Chandler classification) radionecrosis of the larynx treated with adjunctive hyperbaric oxygen therapy is presented. Signs and symptoms of radionecrosis were dramatically ameliorated in seven of eight patients, while one patient, despite subjective improvement, eventually required laryngectomy. There were no deaths. These results are compared to previous series on radionecrosis of the larynx in which hyperbaric oxygen was not used. This series indicates that hyperbaric oxygen therapy is a useful and effective adjunctive treatment modality in the management of laryngeal radionecrosis.

Care for adolescent pregnancy and childbirth.

The rise in adolescent pregnancy in the 20th century has been influenced by declining age at menarche, increased schooling, delay of marriage, inadequate contraception and poverty. The main problems are preterm labor, hypertensive disease, anemia, more severe forms of malaria, obstructed labor in very young girls in some regions, poor maternal nutrition and poor breastfeeding. In many regions HIV infection is an important problem. The infants of adolescent mothers are more prone to low birth weight and increased neonatal mortality and morbidity. Antenatal care is often inadequate. The most important problem is the increased incidence of preterm labor and delivery, the youngest age groups running the highest risk. Technically, care of adolescents during labor need not differ from care of older women; most adolescents are not at increased risk during labor, although, they are more in need of empathic support. Generally, care of pregnant adolescents should be adjusted to their specific needs.

Unsafe abortion in adolescents.

Every year, an estimated 2.0-4.4 million adolescents resort to abortion. In comparison with adults, adolescents are more likely to delay the abortion, resort to unskilled persons to perform it, use dangerous methods and present late when complications arise. Adolescents are also more likely to experience complications. Consequently, adolescents seeking abortion or presenting with complications of abortion should be considered as a medical emergency. Issues requiring special attention in the management of abortion complications in adolescents are identified. Approaches to adolescent abortion should involve all levels of the health care system, as well as the community, and should include not only management of the consequences of unsafe abortion, but also post-abortion contraception and counseling. Prevention of unwanted pregnancy by providing information on sexuality, ensuring that reproductive health services are adolescent-friendly, creating a supportive environment, building young people's social and decision-making skills, and offering counseling in times of crisis are highlighted.

Definitions of fungal rhinosinusitis.

Classification of fungal rhinosinusitis is important for the accurate prediction of prognosis and direct therapy. The most important distinction is between invasive and noninvasive fungal rhinosinusitis. Within the invasive division are acute invasive and chronic invasive (granulomatous and nongranulomatous forms) rhinosinusitis. Within the noninvasive division are saprophytic colonization, fungus balls, and allergic fungal rhinosinusitis. This article briefly outlines the definition and management of each of these manifestations.

Mucormycosis of the nose and paranasal sinuses.

Rhinocerebral mucormycosis is an invasive fungal infection initiated in the paranasal sinuses that frequently progresses to orbital and brain involvement. If recognized early, involvement is limited to the nasal cavity and paranasal sinuses. Diabetics in poor control are at greatest risk, however, any immunocompromised individual may be infected. The mainstays of therapy are reversal of immunosuppression, systemic amphortericin B, and surgical débridement. Survival has improved dramatically, yet deaths still occur if the infection is not recognized and not treated early in its course or if the source of immunocompromise is not reversible. Several case examples illustrate the clinical course of this unusual, but potentially fatal, fungal infection. Taxonomy, clinical presentation, diagnosis, and management of mucormycosis of the paranasal sinuses are reviewed in detail.

Fungus balls of the paranasal sinuses.

Fungus balls of the paranasal sinuses represent a noninvasive manifestation of fungal sinusitis. Patients are immunocompetent but no more allergic than the general population. There is little tissue reaction to the tangled mat of hyphae. If the patient becomes immunocompromised, then the fungus ball may become invasive, as illustrated by an included case report. One hundred sixty-three additional cases of patients with paranasal sinus fungus balls are reviewed from the literature.

Cost-effective pharmacotherapy for allergic rhinitis.

This article provides guidelines for pharmacotherapy to maximize symptom relief from allergic rhinitis. Consideration of frequency, severity, and site of symptoms is important in directing pharmacotherapy efficacy and maximizing cost-effectiveness. The agents available include antihistamines, decongestants, steroids, mast cell stabilizers, anticholinergic agents, and mucolytics. Appropriate indications for each and combinations of various agents are discussed within the context of drug efficacy, side effects, affordability, and ease of compliance. The direct and indirect costs of allergic rhinitis are not well delineated but are explored to put the costs of therapy in perspective.

Geographic variation in allergic fungal rhinosinusitis.

Allergic fungal rhinosinusitis (AFRS) has a worldwide distribution. This survey of 20 otolaryngologic practices throughout the United States confirmed a variation in the frequency of AFRS relative to endoscopic sinus procedures performed for all other diagnoses. The highest incidence occurred in Memphis, Tennessee at 23%, with three other southern practices reporting a frequency of at least 10%. In the northern locations the frequency ranged from 0 to 4%. No correlation with mould counts was demonstrated, possibly because of incomplete mould data relative to most of the surgical locations.

Allergic rhinitis. Recognizing signs, symptoms, and triggering allergens.

Runny noses, sneezing, nasal congestion, and other nuisance symptoms are part and parcel of primary care practice. But how can you quickly discern which symptoms are related to common colds and which stem from allergic rhinitis? Careful history taking usually provides clues, but allergy testing may be needed when triggers are not clear. In this first of two articles on allergic rhinitis, Dr Ferguson explains what to look for, what questions to ask, when to test for allergies, and how to modify a patient's environment to minimize problems. The second article, beginning on page 117, discusses pharmacologic treatment and immunotherapy for allergic rhinitis.