Can alcohol consumption be an alternative treatment for fibromyalgia?

Treatment of chronic pain conditions such as fibromyalgia is challenging due to limitations of drug therapies. An initial exploration into the relationships between self-reported alcohol consumption, symptom severity, and quality of life for individuals with fibromyalgia sheds new light on plausible hypotheses and potential mechanisms of action for future research. Evidence suggests that alcohol consumption may improve social and psychological factors because of activity in the ascending and descending pain pathways in modulating gamma-aminobutyric acid neurotransmission. Further methodologically rigorous studies in this field to improve well-being of individuals with fibromyalgia are warranted.In a previous issue of Arthritis Research & Therapy, Kim and colleagues [1] reported the first study to examine the association between alcohol consumption, symptom severity, and quality of life of individuals with fibromyalgia (FM). Treatment of chronic pain conditions such as FM is challenging because the drug therapies currently available are expensive and associated with numerous limitations such as undesirable side effects and addiction or tolerance issues. Despite undergoing drug treatment, patients are often left with unrelieved pain, restricted mobility, and reduced physical function. Lifestyle interventions, including dietary modifications such as alcohol consumption, have gained popularity as explorations in symptom management.Several observational studies have examined the association between alcohol consumption and chronic pain conditions. In a prospective study, Bergman and colleagues [2] found that regular weekly or daily alcohol consumption is a significant protective factor for the development of chronic pain. Two case–control studies have also shown that moderate alcohol consumption correlates with a reduced risk of rheumatoid arthritis [3,4]. However, a systematic review of nine epidemiological studies has concluded that alcohol consumption is not associated with low back pain [5]. Kim and colleagues are the first to examine the association between alcohol consumption and FM symptom severity and quality of life. Among the 946 adult FM patients (94 % women, mean age of 49 years old) reporting low or moderate alcohol consumption (≤3 or >3 to 7 drinks per week), there was lower FM symptom severity and better quality-of-life scores compared with those who reported no alcohol consumption (non-drinkers). However, these associations were not observed in patients who were heavy drinkers (>7 drinks per week) compared with non-drinkers. Drinkers had higher education, less unemployment, lower body mass index, and lower frequency of opioid use than non-drinkers. Thus, their analyses were adjusted for these potential confounders.Because alcohol consumption consists of complex behaviors that intersect with many social, economic, psychological, and demographic factors, disentangling this complex web of relationships is a challenge. Interestingly, after exploring possible mechanisms for their findings, Kim and colleagues speculated that alcohol consumption may attenuate FM symptoms and improve quality of life by mediating psychological benefits and stress relief or by promoting factors associated with social integration. Another possible mechanism proposed is central nervous mediation via the modulating gamma-aminobutyric acid (GABA) system. Several neurotransmitters (including GABA) in the ascending and descending pain pathways have been implicated in FM [6]. Thus, behavioral and pharmacological therapies that modulate or mimic the effects of GABA production can be promising for FM treatment.This initial exploration into the relationships between alcohol consumption, symptom severity, and quality of life for FM has posed a number of questions that need to be answered by future studies with stronger study designs. Kim and colleagues discussed limitations associated with cross-sectional study design, and we would like to underscore additional concerns relating to the potential for non-random misclassifications of alcohol consumption among FM patients with different levels of symptom severity or quality of life. Such information bias is not uncommon in cross-sectional studies providing data on both exposure and outcome variables from questionnaires. Because the questionnaires are administered at the same time in a cross-sectional study and relied on respondent recall, the measurement errors of exposure (that is, alcohol consumption) may be dependent on the measurement errors of the outcomes (that is, quality of life or FM symptoms). If such dependent bias occurs, the observed association between exposure and outcome is likely to be inflated [7]. Owing to lack of prior data demonstrating that such bias exists in cross-sectional studies of alcohol consumption and FM symptom severity, we provide a possible scenario to examine the potential impacts of dependent bias on this relationship. FM patients who on one occasion had more severe symptoms may in fact have consumed more alcohol to ameliorate symptoms and thus may have felt better (fewer symptoms) at the time of the survey, or FM patients with more severe symptoms at the time of the survey may have stopped drinking alcohol (thus no symptom relief) because of their symptoms. The impact of such dependent bias would result in an inflation of the ‘true’ association. Owing to cross-sectional design, this potential bias cannot be evaluated. In addition to the potential for dependent bias, patients with FM may be too embarrassed to reveal their ‘true’ alcohol intake level because of social desirability biases [8]. Such reporting bias [9], however, is likely to be random and independent of symptom severity. There is still great uncertainty in the study results; therefore, we agree with Kim and colleagues that these preliminary results should not be used as grounds for advising patients to drink alcohol.In sum, the study by Kim and colleagues sheds new light on plausible hypotheses and mechanisms to consider in future methodologically rigorous studies to improve the well-being of individuals with FM. Because it may not be feasible to randomize alcohol consumption in human subject research, methodologically rigorous prospective longitudinal studies are needed. Measuring alcohol consumption at different time points is essential in order to minimize dependent biases from patient-reported exposure and outcome measures.     

Is immunotherapy an effective treatment for Alzheimer's disease?

Immunotherapy in patients with Alzheimer's disease (AD) is rapidly becoming a hot topic of modern geriatric and clinical gerontology. Current views see immunization with Aβ peptide, the amyloidogenic protein found in senile plaque of AD patient's brains, or the infusion of preformed antibody specific for human Aβ, as possible therapeutic approaches to improve the cognitive status in the disease. Animal models of the disease have provided positive results from both approaches. Thus, an initial clinical trial using immunization with human Aβ in AD patients was started, but then shortly halted because of an unusually high incidence (6%) of meningoencephalitis. A long and currently ongoing debate in the scientific community about the pro or contra of vaccination or passive immunization with Aβ in AD is thereafter started. Here, the authors would like to stress few points of concern regarding these approaches in clinical practice.     

Is voice therapy an effective treatment for dysphonia? A randomised controlled trial

ObjectivesTo assess the overall efficacy of voice therapy for dysphonia.Design Single blind randomised controlled trial.Setting Outpatient clinic in a teaching hospital.Participants204 outpatients aged 17-87 with a primary symptom of persistent hoarseness for at least two months.Interventions After baseline assessments, patients were randomised to six weeks of either voice therapy or no treatment. Assessments were repeated at six weeks on the 145 (71%) patients who continued to this stage and at 12-14 weeks on the 133 (65%) patients who completed the study. The assessments at the three time points for the 70 patients who completed treatment and the 63 patients in the group given no treatment were compared.ResultsVoice therapy improved voice quality as assessed by rating by patients (P=0.001) and rating by observer (P<0.001). The treatment effects for these two outcomes were 4.1 (95% confidence interval 1.7 to 6.6) points and 0.82 (0.50 to 1.13) points. Amplitude perturbation showed improvement at six weeks (P=0.005) but not on completion of the study. Patients with dysphonia had appreciable psychological distress and lower quality of life than controls, but voice therapy had no significant impact on either of these variables.ConclusionVoice therapy is effective in improving voice quality as assessed by self rated and observer rated methods.

What is already known on this topic

Many patients with dysphonia are treated by voice therapyThe effectiveness of voice therapy in a diverse group of patients is unknown

What this study adds

Voice therapy is an effective treatment for dysphonia in terms of report by patients and perceptual ratings by an expertPsychological distress and reduction in general health status are common in patients with dysphonia but are not significantly affected by a course of voice therapy     

Can calcium signaling be harnessed for cancer immunotherapy?

Experimental evidence shows the importance of the immune system in controlling tumor appearance and growth. Immunotherapy is defined as the treatment of a disease by inducing, enhancing or suppressing an immune response. In the context of cancer treatment, it involves breaking tolerance to a cancer-specific self-antigen and/or enhancing the existing anti-tumor immune response, be it specific or not. Part of the complexity in developing such treatment is that cancers are selected to escape adaptive or innate immune responses. These escape mechanisms are numerous and they may cumulate in one cancer. Moreover, different cancers of a same type may present different combinations of escape mechanisms. The limited success of immunotherapeutics in the clinic as stand-alone products may in part be explained by the fact that most of them only activate one facet of the immune response. It is important to identify novel methods to broaden the efficacy of immunotherapeutics. Calcium signaling is central to numerous cellular processes, leading to immune responses, cancer growth and apoptosis induced by cancer treatments. Calcium signaling in cancer therapy and control will be integrated to current cancer immunotherapy approaches. This article is part of a Special Issue entitled: Calcium Signaling in Health and Disease. Guest Editors: Geert Bultynck, Jacques Haiech, Claus W. Heizmann, Joachim Krebs, and Marc Moreau.     

Can shooting be an effective management tool for foxes? Preliminary insights from a management programme

Historically, shooting has been a popular method for controlling foxes in Australia, but past research has shown it to be an ineffective method for significantly reducing fox population numbers. These past studies investigated shooting when conducted in isolated, one‐off programmes. In more recent years large, coordinated group fox management programmes has become popular in both agricultural and conservation areas. These landscape scale programmes give more chance of long‐term respite from predation damage by slowing down the immigration rates of foxes into the culled area. Studies have been conducted investigating the effectiveness of large‐scale group fox management programmes that primarily used 1080 baiting as the method of control to protect vulnerable livestock and small animal. This study investigated the potential of a large‐scale group programme that used shooting as the main form of control to reduce the impact of fox predation.     

Stem cells for lung cancer?

Stem cells are believed to be crucial players in tumor development. There is much interest in identifying those compartments that harbor stem cells involved in lung cancer, given the high incidence and recurrence rate of this disease. In this issue of Cell, Kim and colleagues describe a niche in the bronchioalveolar duct junction of adult mouse lung that harbors stem cells from which adenocarcinomas are likely to arise. They enriched, propagated, and differentiated these stem cells in vitro and found that they were activated by the oncogenic protein K-ras. This study provides exciting insights into how the stem cell compartment operates during both normal lung-tissue homeostasis and the development of lung cancer. The new work offers perspectives on possible therapeutic interventions to combat lung cancer.     

Is weight loss an effective treatment for hypertension? The evidence against

Although there are many studies reporting correlations between relative body weight and blood pressure, the correlations are generally of low order. Furthermore, these observational studies provide, at best, circumstantial evidence concerning the effect of weight reduction on elevated blood pressure. After outlining key methodologic criteria for testing the hypothesis that weight loss lowers blood pressure among hypertensive obese subjects, this article reviews the best intervention studies that are available. Despite the demonstration in these randomized trials that weight reduction programs can lower weight successfully, the results for blood pressure lowering are in considerable disagreement. Two studies reported significant lowering of both systolic and diastolic blood pressure, one found significant lowering of systolic pressure only, and two failed to find significant differences in either. The definitive study of substantial weight loss among patients receiving no other antihypertensive treatment or standardized medical treatment with long-term follow-up has yet to be done. At best, weight loss offers very limited benefit for overweight hypertensives. At worst, weight loss programs are expensive to run, cause considerable patient discomfort and may delay the implementation of more effective therapy.     

Can metabolic plasticity be a cause for cancer? Warburg-Waddington legacy revisited

Fermentation of glucose to lactate in the presence of sufficient oxygen, known as aerobic glycolysis or Warburg effect, is a universal phenotype of cancer cells. Understanding its origin and role in cellular immortalization and transformation has attracted considerable attention in the recent past. Intriguingly, while we now know that Warburg effect is essential for tumor growth and development, it is thought to arise because of genetic and/or epigenetic changes. In contrast to the above, we propose that Warburg effect can also arise due to normal biochemical fluctuations, independent of genetic and epigenetic changes. Cells that have acquired Warburg effect proliferate rapidly to give rise to a population of heterogeneous progenitors of cancer cells. Such cells also generate more lactate and alter the fitness landscape. This dynamic fitness landscape facilitates evolution of cancer cells from its progenitors, in a fashion analogous to Darwinian evolution. Thus, sporadic cancer can also occur first by the acquisition of Warburg effect, then followed by mutation and selection. The idea proposed here circumvents the inherent difficulties associated with the current understanding of tumorigenesis, and is also consistent with many experimental and epidemiological observations. We discuss this model in the context of epigenetics as originally enunciated by Waddington. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13148-011-0030-x) contains supplementary material, which is available to authorized users.     

Can a membrane oxygenator be a model for lung NO and CO transfer?

To model lung nitric oxide (NO) and carbon monoxide (CO) uptake, a membrane oxygenator circuit was primed with horse blood flowing at 2.5 l/min. Its gas channel was ventilated with 5 parts/million NO, 0.02% CO, and 22% O2 at 5 l/min. NO diffusing capacity (Dno) and CO diffusing capacity (Dco) were calculated from inlet and outlet gas concentrations and flow rates: Dno = 13.45 ml.min(-1).Torr(-1) (SD 5.84) and Dco = 1.22 ml.min(-1).Torr(-1) (SD 0.3). Dno and Dco increased (P = 0.002) with blood volume/surface area. 1/Dno (P < 0.001) and 1/Dco (P < 0.001) increased with 1/Hb. Dno (P = 0.01) and Dco (P = 0.004) fell with increasing gas flow. Dno but not Dco increased with hemolysis (P = 0.001), indicating Dno dependence on red cell diffusive resistance. The posthemolysis value for membrane diffusing capacity = 41 ml.min(-1).Torr(-1) is the true membrane diffusing capacity of the system. No change in Dno or Dco occurred with changing blood flow rate. 1/Dco increased (P = 0.009) with increasing Po2. Dno and Dco appear to be diffusion limited, and Dco reaction limited. In this apparatus, the red cell and plasma offer a significant barrier to NO but not CO diffusion. Applying the Roughton-Forster model yields similar specific transfer conductance of blood per milliliter for NO and CO to previous estimates. This approach allows alteration of membrane area/blood volume, blood flow, gas flow, oxygen tension, red cell integrity, and hematocrit (over a larger range than encountered clinically), while keeping other variables constant. Although structurally very different, it offers a functional model of lung NO and CO transfer.     

Organoid model: A new hope for pancreatic cancer treatment?

Pancreatic cancer is a rapidly progressing disease with a poor prognosis. We still have many questions about the pathogenesis, early diagnosis and precise treatment of this disease. Organoids, a rapidly emerging technology, can simulate the characteristics of pancreatic tumors. Using the organoid model of pancreatic cancer, we can study and explore the characteristics of pancreatic cancer, thereby effectively guiding clinical practice and improving patient prognosis. This review introduces the development of organoids, comparisons of organoids with other preclinical models and the status of organoids in basic research and clinical applications for pancreatic cancer.     

Can systems biology approach help in finding more effective treatment for acute myeloid leukemia?

Acute myeloid leukemia (AML) is a hematological cancer comprising of cancer stem cells (CSCs) that are responsible for the disease progression, drug resistance and post treatment relapses. Advances in genomic technologies have identified AML as a genetically heterogenous disease with dysregulated gene expression networks. Furthermore, observation of intracellular signaling in individual CSCs by mass cytometry has demonstrated the dysregulation of the mitogen associated protein kinase (MAPK) pathways. It has been envisaged that the future treatment for AML would entail upon formulating individualized treatment plans leading to decreased drug related toxicities for patients. However the emerging role of signaling pathways as dynamic molecular switches influencing the cell cycle process, thereby leading to varying stages of cell differentiation, is making community rethink about the current strategies used for the treatment of AML. This commentary will focus on discovering novel biomarkers and identifying new therapeutic targets, to analyze and treat AML, on a platform enabled by systems biology approach.     

Can mosquitoes be bitten? A new hope for anti-malarial drug design

The crystal structure of PfPK5, a cyclin-dependent kinase from Plasmodium falciparum, is the first CDK structure determined from a nonhuman source and represents a potential new target for anti-malarial drug development.