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\"From one of the world's foremost physicians and researchers, a monumental work that radically redefines our conventional conceptions of health and illness to offer new methods for living a long, healthy life. After considering the discoveries that have led to progress in treating some diseases, Dr. David B. Agus asked an essential question: Why aren't we better at curing illnesses like cancer? Based on his groundbreaking research and the clinical trials he has conducted at the nation's leading medical centers, he came to the realization that we've been approaching medicine from a faulty perspective, and the best way to prevent and combat maladies like cancer, heart disease, autoimmune disorders, and neurodegeneration is to first embrace a totally new view of the human body. What Is Health? asks readers to reconsider everything they think they know about health--and give up believing many myths that may actually be causing them harm and decreasing longevity. These myths revolve around a spectrum of misconceptions, from the benefits of vitamins and supplements to the role of DNA in one's fate. In attempting to reduce our understanding of ailments to a mutation, germ, or deficiency, Dr. Agus proves we have forgotten that the body is a complex system. He presents a systemic picture of the body's vast mechanisms that drive it either toward or away from sickness, empowering readers to take charge of their individual health in very personal, customized ways they've never imagined before. Along the way, Dr. Agus offers insights and access to breathtaking and powerful new technologies that promise to transform medicine in our generation. He also shows that there is no \"right\" answer in health decisions. This is a radically different approach that will not only change how we care for ourselves, but also how we develop the next generation of treatments and cures. What Is Health? represents a dramatic departure from orthodox thinking that promises to revolutionize our quest for long, healthy lives\"-- Provided by publisher.

Peroxiredoxins, a highly conserved family of thiol oxidoreductases, play a key role in oxidant detoxification by partnering with the thioredoxin system to protect against oxidative stress. In addition to their peroxidase activity, certain types of peroxiredoxins possess other biochemical activities, including assistance in preventing protein aggregation upon exposure to high levels of oxidants (molecular chaperone activity), and the transduction of redox signals to downstream proteins (redox switch activity). Mice lacking the peroxiredoxin Prdx1 exhibit an increased incidence of tumor formation, whereas baker’s yeast (Saccharomyces cerevisiae) lacking the orthologous peroxiredoxin Tsa1 exhibit a mutator phenotype. Collectively, these findings suggest a potential link between peroxiredoxins, control of genomic stability, and cancer etiology. Here, we examine the potential mechanisms through which Tsa1 lowers mutation rates, taking into account its diverse biochemical roles in oxidant defense, protein homeostasis, and redox signaling as well as its interplay with thioredoxin and thioredoxin substrates, including ribonucleotide reductase. More work is needed to clarify the nuanced mechanism(s) through which this highly conserved peroxidase influences genome stability, and to determine if this mechanism is similar across a range of species.

\"In TOXIC WAIST, Dr. Bruce Blumberg reveals his landmark research as well as that by others in the field to show how hidden factors, such as environmental chemicals, might be important players in our 21st century obesity epidemic. According to leading-edge science, being overweight is not just the result of too many cheeseburgers and not enough exercise. A silent factor is contributing greatly to our obesity epidemic: \"obesogens.\" These chemicals in our diet and environment sabotage our efforts to lose weight by disrupting our hormonal system, altering how we create and store fat, and changing how we respond to dietary choices and calories. Even scarier: research has shown that the effects of obesogen exposure can be passed on to future generations by irreversibly interfering with the expression of our genes. And these chemicals are everywhere, from our food to our furniture to common, household products. TOXIC WAIST offers a synthesis of the latest research in the field, and a three-step action plan to prevent and minimize the damaging effects of obesogens. This book lays out what we know so far about obesogens, shows how they work and how we are exposed to them (get ready to throw out your plastic food storage containers). Most importantly, it arms us with the knowledge we need to protect ourselves from the harmful effects of obesogens\"-- Provided by publisher.

IntroductionThere is limited evidence on how to effectively treat individuals from marginalised populations with dependence on amphetamine and/or methamphetamine (collectively referred to hereafter as amphetamine dependence). The disease burden is extremely high in this population, especially related to psychiatric comorbidities, cardiovascular complications, injection-related infections and poor social functioning. ATLAS4Dependence is a multi-centre randomised, placebo-controlled, double-blind trial that will investigate the effectiveness and safety of substitution treatment with dextroamphetamine compared with placebo in people with amphetamine dependence.Methods and analysisThe trial will recruit 226 adult patients in several outpatient clinics in Norway. Inclusion criteria comprise individuals with amphetamine dependence, defined as use on three or more days per week during the past 28 days, who currently inject or have formerly injected drugs. This includes individuals both with and without comorbid opioid dependence, as well as those currently receiving or not receiving opioid agonist treatment. Participants will be randomly assigned 1:1 to receive either dextroamphetamine or placebo for 12 weeks. Flexible doses within the range of 30–120 mg daily will be provided based on individual assessments. The participants in both arms will be offered standard psychosocial and medical follow-up in accordance with current clinical practice. The endpoint assessments will be conducted at 12 weeks with weekly self-reports and safety assessments and a follow-up assessment at 52 weeks. The primary objective of the study is to assess the impact of 12 weeks daily prescribed oral dextroamphetamine versus placebo on the use of illicit amphetamines as well as on the total amount of amphetamines used (including both illicit and prescribed sources). Secondary outcomes are the differences between the groups at 12 weeks regarding psychological distress, symptoms of psychosis, quality of life, cardiovascular risk factors, injection-related infections, executive functioning, attention-deficit hyperactivity disorder-related symptoms, sleep, violence risk, fatigue, symptoms of craving and withdrawal, treatment retention, days of use of illicit amphetamines and use at 4 weeks and 8 weeks during the intervention period, use of other illicit substances and alcohol, as well as a cost-effectiveness analysis (using private economy, criminal activity and health service utilisation) and a qualitative approach to assess overall experiences with the study intervention. Analysis and reporting will follow the Consolidated Standards of Reporting Trials guidelines. All tests will be two-sided. Descriptive results and the estimated effectiveness will be presented with 95% CIs. The difference between the groups at the primary time point (at the end of the 12-week trial) will be assessed using χ2 test (for use of illicit amphetamines measured by monthly urine tests) and Analysis of Covariance (ANCOVA) (for weekly self-reported total amount of amphetamines). Analyses for the primary endpoint will be undertaken on an intention-to-treat basis and reported on as such, but sensitivity analyses with per protocol analyses will also be presented.Ethics and disseminationThe study is approved by European Medicines Agency, Clinical Trial Information System (CTIS). Written informed consent will be obtained from all patients. Study results will be published in international peer-reviewed medical journals.Trial registration numberCTIS 2023-510404-44-00.

Background Opioid dependence carries the highest disease burden of all illicit drugs. Opioid agonist therapy (OAT) is an evidence-based medical intervention that reduces morbidity and mortality. There is limited knowledge on the health-related quality of life (HRQoL) of long-term patients in OAT. This study measures HRQoL and self-perceived health of long-term patients on OAT, compares the scores to a Norwegian reference population, and assesses changes in these scores at 1-year follow up. Methods We conducted a nested prospective cohort study among nine OAT outpatient clinics in Norway. 609 OAT patients were included, 245 (40%) followed-up one year later. Data on patient characteristics, HRQoL, and self-perceived health was collected. HRQoL was assessed with the EQ-5D-5L, which measures five dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) on a five-point Likert scale (from “no problems” to “extreme problems”). An UK value set was applied to calculate index values (from 0 to 1) for the EQ-5D-5L and compare them to a Norwegian reference population. Self-perceived health was measured with EQ-VAS (from 0 to 100). Results Mean (standard deviation (SD)) EQ-5D-5L index value at baseline was 0.699 (0.250) and EQ-VAS 57 (22) compared to 0.848 (0.200) and 80(19) for the Norwegian reference population. There were large variations in EQ-5D-5L index values, where 43% had > 0.8 and 5% had < 0.2 at baseline. The lowest EQ-5D-5L index values were observed for female patients, age groups older than 40 years and for methadone users. At follow-up, improvements in HRQoL were observed across almost all dimensions and found significant for mobility and pain/discomfort. Mean (SD) overall index value and EQ-VAS at follow up were 0.729 (0.237) and 59 (22) respectively. Conclusion The average HRQoL and self-perceived health of OAT patients is significantly lower than that of the general population, and lower than what has been found among other severe somatic and psychiatric conditions. Around 34% had very good HRQoL, higher than average Norwegian values, and around 5% had extremely poor HRQoL.

Background There is high co-occurrence of substance use disorders (SUD) and mental health disorders. We aimed to assess impact of substance use patterns and sociodemographic factors on mental health distress using the ten-item Hopkins Symptom Checklist (SCL-10) over time. Methods Nested prospective cohort study of 707 participants with severe SUD across nine opioid-agonist-therapy outpatient clinics and low-threshold municipality clinics in Norway, during 2017–2020. Descriptive statistics were derived at baseline and reported by means and standard deviation (SD). A linear mixed model analysis was used to assess the impact of substance use patterns and sociodemographic factors on SCL-10 sum score with beta coefficients with 95% confidence intervals (CI). Results Mean (SD) SCL-10 score was 2.2 (0.8) at baseline with large variations across patients. We observed more symptoms of mental health disorders among people with frequent use of benzodiazepines (beta 3.6, CI:2.4;4.8), cannabis (1.3, CI:0.2;2.5), opioids (2.7, CI:1.1;4.2), and less symptoms among people using frequent stimulant use (− 2.7, CI:-4.1;-1.4) compared to no or less frequent use. Females (1.8, CI:0.7;3.0) and participants with debt worries (2.2, CI:1.1;3.3) and unstable living conditions (1.7, CI:0.0;3.3) had also higher burden of mental health symptoms. There were large individual variations in SCL-10 score from baseline to follow-up, but no consistent time trends indicating change over time for the whole group. 65% of the cohort had a mean score > 1.85, the standard reference score. Conclusions People with SUD have a considerable burden of mental health symptoms. We found no association between substance use patterns and change in mental health symptoms over time. This could suggest that the differences observed were indicating flattening of effects or self-medication to a larger degree than medication-related decline in mental health. This call for better individualized mental health assessment and patient care.

Skin disorders beat out anxiety, depression, back pain, and diabetes as the number one reason Americans see their doctors. Many leave the office with the underlying conditions at the root of their skin issues unresolved. Bowe believes that many skin disorders are manifestations of irregularities originating in the gut. She encourages readers to focus on the microbiome, and highlights the connection between sleep, stress, diet, gastrointestinal health, and the look of skin.

ObjectiveThere is uncertainty whether cancer screening affects participant incentives for favourable lifestyle. The present study investigates long-term effects of colorectal cancer (CRC) screening on lifestyle changes.DesignIn 1999–2001, men and women drawn from the population registry were randomised to screening for CRC by flexible sigmoidoscopy (‘invited-to-screening’ arm) or to no-screening (control arm) in the Norwegian Colorectal Cancer Prevention trial. A subgroup of 3043 individuals in the ‘invited-to-screening’ and 2819 in the control arm, aged 50–55 years, randomised during 2001 had their lifestyle assessed by a questionnaire at inclusion and after 11 years (42% of cohort). The outcome was 11-year changes in lifestyle factors (body weight, smoking status, physical exercise, selected dietary habits) and in total lifestyle score (0–4 points, translating to the number of lifestyle recommendations adhered to). We compared outcomes in the two randomisation arms and attendees with positive versus negative findings.ResultsTotal lifestyle scores improved in both arms. The improvement was smaller in the ‘invited-to-screening’ arm (score 1.43 at inclusion; 1.58 after 11 years) compared with the control arm (score 1.49 at inclusion; 1.67 after 11 years); adjusted difference −0.05 (95% CI −0.09 to −0.01; p=0.03). The change in the score was less favourable in screening attendees with a positive compared with negative screening result; adjusted difference −0.16 (95% CI −0.25 to −0.08; p<0.001).ConclusionsThe present study suggests that possible unfavourable lifestyle changes after CRC screening are modest. Lifestyle counselling may be considered as part of cancer screening programmes.Trial registration numberNCT00119912.