Publications by authors named "James Chmiel"

: Neuropsychiatric symptoms such as depression and anxiety are a significant burden on patients with multiple sclerosis (MS). Their pathophysiology is complex and yet to be fully understood. There is an urgent need for non-invasive treatments that directly target the brain and help patients with MS.

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Introduction: Bulimia nervosa (BN) is a disorder primarily affecting adolescent females, characterized by episodes of binge eating followed by inappropriate compensatory behaviors aimed at preventing weight gain, including self-induced vomiting and the misuse of diuretics, laxatives, and insulin. The precise etiology of BN remains unknown, with factors such as genetics, biological influences, emotional disturbances, societal pressures, and other challenges contributing to its prevalence. First-line treatment typically includes pharmacotherapy, which has shown moderate effectiveness.

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Background: Lung inflammation is associated with tissue damage in cystic fibrosis (CF). LAU-7b, a novel oral drug candidate, was shown to control inflammation and stabilize CFTR protein in the epithelial membrane during inflammatory stress in preclinical models of CF.

Methods: A double-blind, randomized, placebo-controlled Phase 2 study was conducted to evaluate efficacy and safety of LAU-7b in adults with CF.

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: HIV is a severe and incurable disease that has a devastating impact worldwide. It affects the immune system and negatively affects the nervous system, leading to various cognitive and behavioral problems. Scientists are actively exploring different therapeutic approaches to combat these issues.

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Introduction: Binge eating disorder (BED) is the most common eating disorder among those contributing to the development of obesity, and thus acts as a significant burden on the lives and health of patients. It is characterized by complex neurobiology, which includes changes in brain activity and neurotransmitter secretion. Existing treatments are moderately effective, and so the search for new therapies that are effective and safe is ongoing.

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Introduction: Methamphetamine is a highly stimulating psychoactive drug that causes life-threatening addictions and affects millions of people around the world. Its effects on the brain are complex and include disturbances in the neurotransmitter systems and neurotoxicity. There are several known treatment methods, but their effectiveness is moderate.

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: Down syndrome (DS) stands out as one of the most prevalent genetic disorders, imposing a significant burden on both society and the healthcare system. Scientists are making efforts to understand the neural mechanisms behind the pathophysiology of this disorder. Among the valuable methods for studying these mechanisms is electroencephalography (EEG), a non-invasive technique that measures the brain's electrical activity, characterised by its excellent temporal resolution.

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Introduction: Depression is the most prevalent comorbid neuropsychiatric condition in individuals with Parkinson's disease (PD), and its underlying mechanisms are not yet fully understood. Current treatment methods are characterised by moderate effectiveness and possible side effects, prompting the search for new non-invasive and safe treatment methods.

Methods: This narrative review explores the use of transcranial direct current stimulation (tDCS) in the treatment of depression in PD, based on neuropsychological measures.

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Background: Detecting airway inflammation non-invasively in infants with cystic fibrosis (CF) is difficult. We hypothesized that markers of inflammation in CF [IL-1β, IL-6, IL-8, IL-10, IL-17A, neutrophil elastase (NE) and tumor necrosis factor (TNF-α)] could be measured in infants with CF from nasal fluid and would be elevated during viral infections or clinician-defined pulmonary exacerbations (PEx).

Methods: We collected nasal fluid, nasal swabs, and hair samples from 34 infants with CF during monthly clinic visits, sick visits, and hospitalizations.

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Cocaine addiction is a significant problem worldwide. The development of addiction involves a reward system, which consists of certain brain regions like the ventral tegmental area, nucleus accumbens, and prefrontal cortex. Currently, there are no approved medications for treating cocaine dependence, so researchers are actively searching for effective treatments that can impact the brain.

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(1) Introduction: Anorexia nervosa (AN) is a severe, debilitating disease with high incidence and high mortality. The methods of treatment used so far are moderately effective. Evidence from neuroimaging studies helps to design modern methods of therapy.

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Human Mesenchymal Stem Cell (hMSC) immunotherapy has been shown to provide both anti-inflammatory and anti-microbial effectiveness in a variety of diseases. The clinical potency of hMSCs is based upon an initial direct hMSC effect on the pro-inflammatory and anti-microbial pathophysiology as well as sustained potency through orchestrating the host immunity to optimize the resolution of infection and tissue damage. Cystic fibrosis (CF) patients suffer from a lung disease characterized by excessive inflammation and chronic infection as well as a variety of other systemic anomalies associated with the consequences of abnormal cystic fibrosis transmembrane conductance regulator (CFTR) function.

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Most people with cystic fibrosis (CF) are diagnosed following abnormal newborn screening (NBS), which begins with measurement of immunoreactive trypsinogen (IRT) values. A case report found low concentrations of IRT in an infant with CF exposed to the CF transmembrane conductance regulator (CFTR) modulator, elexacaftor-tezacaftor-ivacaftor (ETI), in utero. However, IRT values in infants born to mothers taking ETI have not been systematically assessed.

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Article Synopsis
  • Mesenchymal stem cells (MSCs) from bone marrow are being explored as a treatment for cystic fibrosis (CF), potentially reducing lung inflammation and improving antibiotic effectiveness.
  • A phase 1 clinical trial enrolled 15 adults with CF to test the safety and tolerability of different doses of intravenous hMSCs, with no serious adverse events reported during the study period.
  • The preliminary results indicate that hMSC infusions were safe and well-tolerated, suggesting they are worth further investigation as a potential therapy for CF lung disease.
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Rationale: Inhaled tobramycin and oral azithromycin are common chronic therapies in people with cystic fibrosis and airway infection. Some studies have shown that azithromycin can reduce the ability of tobramycin to kill . This trial was done to test the effects of combining azithromycin with inhaled tobramycin on clinical and microbiological outcomes in people already using inhaled tobramycin.

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Endothelial hemoglobin (Hb)α regulates endothelial nitric oxide synthase (eNOS) biochemistry. We hypothesized that Hb could also be expressed and biochemically active in the ciliated human airway epithelium. Primary human airway epithelial cells, cultured at air-liquid interface (ALI), were obtained by clinical airway brushings or from explanted lungs.

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In contrast to the well-described association between early-life weight for age, body mass index (BMI), and later lung disease in people with cystic fibrosis (CF), the relationship between height-for-age (HFA) percentiles and respiratory morbidity is not as well-studied. We hypothesized that changes in HFA in children with CF in the first 6 years of life would be associated with pulmonary function at the age of 6-7 years. To determine if an association exists between changes in HFA in early life and pulmonary function in school-aged children with CF.

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Asthma remains one of the most important challenges to pediatric public health in the US. A large majority of children with persistent and chronic asthma demonstrate aeroallergen sensitization, which remains a pivotal risk factor associated with the development of persistent, progressive asthma throughout life. In individuals with a tendency toward Type 2 inflammation, sensitization and exposure to high concentrations of offending allergens is associated with increased risk for development of, and impairment from, asthma.

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Background: Few therapies specifically address the chronic airway inflammation in cystic fibrosis (CF) that contributes to progressive destruction of lung tissue and loss of lung function. Lenabasum is a cannabinoid type 2 receptor (CB2) agonist that resolves inflammation in a number of in vitro and in vivo models.

Methods: A Phase 2 double-blind, randomized, placebo-controlled study assessed the safety and tolerability of lenabasum in adults with CF.

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The first regulatory approval for a drug developed specifically for cystic fibrosis (CF) occurred in 1993, and since then, several other drugs have been approved. Median predicted survival in people with CF in the United States has increased from approximately 30 years to 44.4 years over that same period.

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Background: Morbidity from asthma is disproportionately higher among black patients than among white patients, and black patients constitute the minority of participants in trials informing treatment. Data indicate that patients with inadequately controlled asthma benefit more from addition of a long-acting beta-agonist (LABA) than from increased glucocorticoids; however, these data may not be informative for treatment in black patients.

Methods: We conducted two prospective, randomized, double-blind trials: one involving children and the other involving adolescents and adults.

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Background: Tezacaftor/ivacaftor is a new treatment option in many regions for patients aged ≥12 years who are homozygous (F/F) or heterozygous for the F508del-CFTR mutation and a residual function (F/RF) mutation. This Phase 3, 2-part, open-label study evaluated the pharmacokinetics (PK), safety, tolerability, and efficacy of tezacaftor/ivacaftor in children aged 6 through 11 years with these mutations.

Methods: Part A informed weight-based tezacaftor/ivacaftor dosages for part B.

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Background: In many patients with mild, persistent asthma, the percentage of eosinophils in sputum is less than 2% (low eosinophil level). The appropriate treatment for these patients is unknown.

Methods: In this 42-week, double-blind, crossover trial, we assigned 295 patients who were at least 12 years of age and who had mild, persistent asthma to receive mometasone (an inhaled glucocorticoid), tiotropium (a long-acting muscarinic antagonist), or placebo.

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