Why do we sneeze?

According to textbooks, the function of a sneeze is to send a strong blast of air through the nose to remove foreign bodies. Three simple tests are described that show that the current views are wrong. The pressure developed in the mouth/pharynx of the author during a sneeze was recorded as about 135 mmHg reached in about 0.1s. A forced maximal expiration but with the nose and mouth closed produced a nasal secretion although of smaller amount than in the sneeze, in spite of a greater pressure; this is probably because the speed of tension development was much slower than in the sneeze. It is proposed that the high pressure stimulates secretory neurons via branches in the roof of the mouth. The nasal secretion dilutes irritant material in the nose and thus prevents it getting into the lungs.     

Adherence intervention research: what have we learned and what do we do next?

Although there is general agreement from studies demonstrating that adherence to inhaled corticosteroid therapy is often inadequate to establish consistent control, relatively little concurrence exists in reports of interventions to correct the problem. Half of the studies reviewed found that the experimental intervention did not change adherence, and behavior change reported by patients was often not accompanied by changes in treatment success. Studies used a variety of methods that differed in quality with findings that were often contradictory. Key limitations in many studies included reliance on inadequate adherence measures, inclusion of convenience samples of well-motivated patients, and assessments of intervention outcomes artificially boosted by attrition of least adherent participants. Research is encouraged into innovative interventions that are brief, easily implemented, and can be tailored to individual patients and diverse clinical settings. Of particular importance is inclusion of hard-to-reach patients, including urban and rural poor and the use of valid measures of adherence at intervals sufficient to establish enduring benefit.     

Working with dreams in therapy: what do we know and what should we do?

Although a potentially helpful therapeutic tool, dream interpretation or dream work is only used occasionally in most forms of psychotherapy. Despite an interest from clinicians and clients alike in using dreams within therapy, many therapists feel unprepared to attend to their clients' dreams. The main goals of this article are to make clinicians aware that integrating dreams into their clinical practice is both accessible and potentially valuable and to allow them to make an informed decision as to what role they want dream work to play in therapy. The paper begins with a brief overview of some of the more common approaches to dream work. The literature on the usefulness and effectiveness of the clinical use of dreams is then reviewed. Finally, based on the integration of the clinical and empirical literature, several guidelines for conducting dream work are presented.     

Allergen avoidance in asthma: what do we do now?

Although allergen exposure can clearly aggravate the condition of sensitized patients with asthma, there is uncertainty and controversy about exactly which allergen avoidance interventions should be recommended to patients with asthma. Interventions that appear logical may fail to be clinically efficacious for several reasons. Although narrow interventions, such as allergen-impermeable mattress covers to reduce exposure to dust mite allergens, may offer little benefit if used alone, recent evidence suggests that a multifaceted, home-based environmental intervention focusing on multiple exposures may provide clinical benefits to patients with asthma. The role of allergen avoidance in infancy in the primary prevention of asthma is a subject of active investigation, but data remain too preliminary to make public health recommendations in this regard.     

When should we do knee replacements?

It is not known whether it is better to perform total knee replacements early or late in the course of arthritis. To examine the determinants of patient-related outcomes after knee replacement, we examined 812 patients in the Avon knee registry, in whom pre-operative and 5-year post-operative American Knee Society Scores were available. Ninety percent had a good outcome at 5 years. Women had significantly more severe disease at the time of surgery than men. Older people (>79 years) had the worst disease at the time of surgery, and made the least health gain, although their overall outcomes were still good. Those with the most severe disease at the time of operation made greater gains to those with less disease, but remained in worse health at 5 years, suggesting that earlier surgery may be preferable.     

How do we monitor asthma control?

The present consensus on asthma management includes avoidance of triggers, education, regular follow-up, and an action plan that relies on symptoms and lung function measurements for the monitoring of disease severity. Inclusion of objective measurements for monitoring seems to be important because patients and physicians may not always recognize asthma symptoms or their severity. However, the additional value of monitoring peak flow and symptoms in guiding asthma therapy has not been well established. Furthermore, it can be questioned whether a treatment strategy which is solely based on optimizing symptoms and lung function leads to optimal control of asthma in each individual patient, since airway hyperresponsiveness (AHR) and airways inflammation may persist. The chronicity of such abnormalities may lead to airways remodelling, thereby worsening the long-term outcome of asthma. It has been shown that AHR provides prognostic information on asthma control, because it can serve as a valuable noninvasive surrogate marker of airways inflammation when added to the guides of asthma therapy. A limited increase in dose of inhaled steroids, instead of applying an increased dose indiscriminately, can be successfully tailored to the needs of the individual patient based on the degree of AHR. Such a strategy leads to both a better clinical outcome and a better histologic outcome. The present worldwide effort is to find alternative markers of airways inflammation in asthma that can be easily implemented in routine practice. In the near future, longitudinal studies will determine which parameter is potentially most useful in guiding asthma management.     

What should we do about monkeypox?

<正>Over the past 3 years, the COVID-19 pandemic has posed a significant global challenge to the public health system. However, other diseases, such as hepatitis of unknown origin in children and monkeypox,havebeenrecentlyreportedinEuropean,African,and American countries. These data showed that monkeypox and other emerging or re-emerging viruses are novel global threats.Monkeypoxiscausedbyinfectionwiththemonkeypoxvirus(MPXV),alinear,enveloped,double-strandedDNA(dsDNA)virusbelongingtotheOrth...     

Influenza vaccine: Where are we and where do we go?

The alarming rise of morbidity and mortality caused by influenza pandemics and epidemics has drawn attention worldwide since the last few decades. This life‐threatening problem necessitates the development of a safe and effective vaccine to protect against incoming pandemics. The currently available flu vaccines rely on inactivated viral particles, M2e‐based vaccine, live attenuated influenza vaccine (LAIV) and virus like particle (VLP). While inactivated vaccines can only induce systemic humoral responses, LAIV and VLP vaccines stimulate both humoral and cellular immune responses. Yet, these vaccines have limited protection against newly emerging viral strains. These strains, however, can be targeted by universal vaccines consisting of conserved viral proteins such as M2e and capable of inducing cross‐reactive immune response. The lack of viral genome in VLP and M2e‐based vaccines addresses safety concern associated with existing attenuated vaccines. With the emergence of new recombinant viral strains each year, additional effort towards developing improved universal vaccine is warranted. Besides various types of vaccines, microRNA and exosome‐based vaccines have been emerged as new types of influenza vaccines which are associated with new and effective properties. Hence, development of a new generation of vaccines could contribute to better treatment of influenza.     

Cold urticaria – What we know and what we do not know

Cold urticaria (ColdU) is a common form of chronic inducible urticaria characterized by the development of wheals, angioedema or both in response to cold exposure. Recent research and guideline updates have advanced our understanding and management of ColdU. Today, its pathophysiology is thought to involve the cold-induced formation of autoallergens and IgE to these autoallergens, which provoke a release of proinflammatory mediators from skin mast cells. The classification of ColdU includes typical and atypical subtypes. We know that cold-induced wheals usually develop on rewarming and resolve within an hour and that anaphylaxis can occur. The diagnosis relies on the patient's history and cold stimulation testing. Additional diagnostic work-up, including a search for underlying infections, should only be done if indicated by the patient's history. The management of ColdU includes cold avoidance, the regular use of nonsedating antihistamines and the off-label use of omalizumab. However, many questions regarding ColdU remain unanswered. Here, we review what is known about ColdU, and we present important unanswered questions on the epidemiology, underlying pathomechanisms, clinical heterogeneity and treatment outcomes. Our aim is to guide future efforts that will close these knowledge gaps and advance the management of ColdU.     

Progress in Parkinson's disease-Where do we stand?

Parkinson's disease was first described in 1817 by James Parkinson. It is one of the most common neurodegenerative disorders, affecting the nigrostriatal pathways involved in the control of movement. Since the introduction of L-DOPA as a therapy in the mid-1960s, clinical management of the symptoms has progressed, but, at present, it remains impossible to stop the disease progression or to restore lost functions. A better understanding of neurodegeneration and of midbrain neuronal development has allowed the development of new pharmaceutical compounds with neuroprotective properties and has shown the potential of neurone replacement therapies in Parkinson's disease. Even though major obstacles remain before these can be transferred to the clinic, the progress made in the last 10 years brings hope of improved therapies for Parkinson's disease. In this paper we review the current knowledge of Parkinson's disease including its etiology, some of the current symptomatic therapeutic modalities, and recent progress in neuroprotective and cell replacement therapies.     

Peptide-based vaccination: where do we stand?

PURPOSE OF REVIEW: Allergen-specific immunotherapy represents the only causative approach towards allergy treatment. Specific immunotherapy can, however, include allergic reactions and occasionally life-threatening anaphylaxis. Peptides have been evaluated as a potential therapeutic approach in atopic allergic disease because they have the potential to inhibit T-cell function but not induce anaphylaxis. RECENT FINDINGS: Data from early clinical trials of peptide vaccination revealed that therapy was associated with a modest improvement in allergic disease, and was accompanied by a high frequency of adverse reactions. More recent studies have demonstrated improved clinical outcomes, improved safety, and have defined the mechanisms of adverse events observed in earlier studies. Mechanisms of peptide vaccination include the hyporesponsiveness of allergen-specific responses and the induction of regulatory T cells and cytokines. Novel peptide design has allowed the generation of fragments that contain T-cell stimulatory epitopes, lack B cell epitopes, and can induce protective IgG responses in both mice and humans. Other approaches have focused on hypoallergenic B-cell epitopes that induce inhibitory IgG antibodies. Peptides that specifically induce regulatory cytokine production would also enhance peptide vaccines. Several recent studies have described immunodominant epitopes from major allergens that may form candidate peptides for use in peptide vaccination. SUMMARY: The manipulation of peptide epitopes may provide a strategy for the rational design of peptide allergy vaccines further improving safety and efficacy.     

Mannose-binding lectin: do we need it?

Mannose-binding lectin (MBL) deficiency has now been recognised for 15 years. Numerous studies have shown that MBL deficiency is associated with an increased susceptibility to a range of infections. However, the importance of MBL, in defence against infection, is still debated. This article discusses recent developments in MBL research and explores how MBL may be operating in the setting of modern medical practice.     

.VO2max: what do we know, and what do we still need to know?

Maximal oxygen uptake (.VO(2,max)) is a physiological characteristic bounded by the parametric limits of the Fick equation: (left ventricular (LV) end-diastolic volume--LV end-systolic volume) x heart rate x arterio-venous oxygen difference. 'Classical' views of .VO(2,max) emphasize its critical dependence on convective oxygen transport to working skeletal muscle, and recent data are dispositive, proving convincingly that such limits must and do exist. 'Contemporary' investigations into the mechanisms underlying peripheral muscle fatigue due to energetic supply/demand mismatch are clarifying the local mediators of fatigue at the skeletal muscle level, though the afferent signalling pathways that communicate these environmental conditions to the brain and the sites of central integration of cardiovascular and neuromotor control are still being worked out. Elite endurance athletes have a high .VO(2,max) due primarily to a high cardiac output from a large compliant cardiac chamber (including the myocardium and pericardium) which relaxes quickly and fills to a large end-diastolic volume. This large capacity for LV filling and ejection allows preservation of blood pressure during extraordinary rates of muscle blood flow and oxygen transport which support high rates of sustained oxidative metabolism. The magnitude and mechanisms of cardiac phenotype plasticity remain uncertain and probably involve underlying genetic factors, as well as the length, duration, type, intensity and age of initiation of the training stimulus.