Peptides and proteins are preponderantly emerging in the drug market, as shown by the increasing number of biopharmaceutics already approved or under development. Biomolecules like recombinant ...monoclonal antibodies have high therapeutic efficacy and offer a valuable alternative to small-molecule drugs. However, due to their complex three-dimensional structure and the presence of many functional groups, the occurrence of spontaneous conformational and chemical changes is much higher for peptides and proteins than for small molecules. The characterization of biotherapeutics with modern and sophisticated analytical methods has revealed the presence of contaminants that mainly arise from oxidation- and elimination-prone amino-acid side chains. This review focuses on protein chemical modifications that may take place during storage due to (1) oxidation (methionine, cysteine, histidine, tyrosine, tryptophan, and phenylalanine), (2) intra- and inter-residue cyclization (aspartic and glutamic acid, asparagine, glutamine, N-terminal dipeptidyl motifs), and (3) β-elimination (serine, threonine, cysteine, cystine) reactions. It also includes some examples of the impact of such modifications on protein structure and function.
Objective
Given the reported increased rates of physical morbidity and higher mortality rates among people with severe mental illness (SMI) (schizophrenia and severe mood disorders), with a life ...expectancy shorter of 15‐20 years with respect to the general population, the aim of this paper was to call attention to the problem of cancer in SMI.
Methods
We conducted a narrative review of the most significant papers published in the areas of cancer screening, incidence, mortality and palliative care in SMI.
Results
Data from the literature confirm disparities in screening (eg, mammography; pap‐smear test; colorectal cancer screening) and prevention (eg, clinical breast examination; smoking cessation). The incidence of cancer was found to be variable with a portion of the studies reporting a higher prevalence while others a similar or a lower prevalence of cancer compared to the general population. A lower percentage of patients with SMI received proper cancer treatment resulting in survival after cancer diagnosis significantly worse than people without SMI. Likewise, end‐of‐life care has been shown to be lacking with poorer levels of physical, psychological and spiritual care.
Conclusions
The problems of stigma and discrimination, poorer dignity, poorer health behavior, lack of integration in health‐care services for people with SMI needs to be addressed and solved in cancer care. Psycho‐oncology has a very specific and mandatory role in integrating the recommendation of the World Health Organization to improve the links between oncology and mental health settings for more specific psycho‐oncology programs addressed for this vulnerable segment of the population.
Cancer is a devastating disease causing significant psychological problems among patients and their families. In the past few decades, there have been growing implementation and dissemination of ...screening methods for the psychological consequences of cancer, including distress, depression, anxiety, post-traumatic stress, and demoralisation. Also, guidelines for the management of psychological distress have been developed and endorsed by a number of scientific cancer associations. This review examines some of the most significant related issues, also focusing on recent advances in psychosocial and psychopharmacological interventions as a part of a mandatory, integrated, and comprehensive approach to cancer care.
Except for dementia and depression, little is known about common mental disorders in elderly people.
To estimate current, 12-month and lifetime prevalence rates of mental disorders in different ...European and associated countries using a standardised diagnostic interview adapted to measure the cognitive needs of elderly people.
The MentDis_ICF65+ study is based on an age-stratified, random sample of 3142 older men and women (65-84 years) living in selected catchment community areas of participating countries.
One in two individuals had experienced a mental disorder in their lifetime, one in three within the past year and nearly one in four currently had a mental disorder. The most prevalent disorders were anxiety disorders, followed by affective and substance-related disorders.
Compared with previous studies we found substantially higher prevalence rates for most mental disorders. These findings underscore the need for improving diagnostic assessments adapted to the cognitive capacity of elderly people. There is a need to raise awareness of psychosocial problems in elderly people and to deliver high-quality mental health services to these individuals.
Depression in HIV Infected Patients: a Review Nanni, Maria Giulia; Caruso, Rosangela; Mitchell, Alex J. ...
Current psychiatry reports,
2015/1, Letnik:
17, Številka:
1
Journal Article
Recenzirano
Depression is the most common neuropsychiatric complication in HIV-infected patients and may occur in all phases of the infection. Accurately, diagnosing major depressive disorder in the context of ...HIV is an ongoing challenge to clinicians and researchers, being complicated by the complex biological, psychological, and social factors associated with the HIV illness. Evidences exist to support the importance of improving the identification of depressive symptoms and their adequate treatment. Depression has long been recognized as a predictor of negative clinical outcomes in HIV-infected patients, such as reducing medication adherence, quality of life, and treatment outcome, and possibly worsening the progression of the illness and increasing mortality. By analyzing the most relevant studies (MEDLINE, EMBASE, PsycLit, Cochrane Library), the review discusses the epidemiology and the main clinical features of depression in HIV-infected patients, the causal pathways linking depression and HIV infection, the validity of screening tools, and the efficacy of different treatment approaches, including psychosocial interventions, psychopharmacology as well as HIV-specific health psychology health service models.
Summary Background Substantial uncertainty exists about prevalence of mood disorders in patients with cancer, including those in oncological, haematological, and palliative-care settings. We aimed to ...quantitatively summarise the prevalence of depression, anxiety, and adjustments disorders in these settings. Methods We searched Medline, PsycINFO, Embase, and Web of Knowledge for studies that examined well-defined depression, anxiety, and adjustment disorder in adults with cancer in oncological, haematological, and palliative-care settings. We restricted studies to those using psychiatric interviews. Studies were reviewed in accordance with PRISMA guidelines and a proportion meta-analysis was done. Findings We identified 24 studies with 4007 individuals across seven countries in palliative-care settings. Meta-analytical pooled prevalence of depression defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD) criteria was 16·5% (95% CI 13·1–20·3), 14·3% (11·1–17·9) for DSM-defined major depression, and 9·6% (3·6–18·1) for DSM-defined minor depression. Prevalence of adjustment disorder alone was 15·4% (10·1–21·6) and of anxiety disorders 9·8% (6·8–13·2). Prevalence of all types of depression combined was of 24·6% (17·5–32·4), depression or adjustment disorder 24·7% (20·8–28·8), and all types of mood disorder 29·0% (10·1–52·9). We identified 70 studies with 10 071 individuals across 14 countries in oncological and haematological settings. Prevalence of depression by DSM or ICD criteria was 16·3% (13·4–19·5); for DSM-defined major depression it was 14·9% (12·2–17·7) and for DSM-defined minor depression 19·2% (9·1–31·9). Prevalence of adjustment disorder was 19·4% (14·5–24·8), anxiety 10·3% (5·1–17·0), and dysthymia 2·7% (1·7–4·0). Combination diagnoses were common; all types of depression occurred in 20·7% (12·9–29·8) of patients, depression or adjustment disorder in 31·6% (25·0–38·7), and any mood disorder in 38·2% (28·4–48·6). There were few consistent correlates of depression: there was no effect of age, sex, or clinical setting and inadequate data to examine cancer type and illness duration. Interpretation Interview-defined depression and anxiety is less common in patients with cancer than previously thought, although some combination of mood disorders occurs in 30–40% of patients in hospital settings without a significant difference between palliative-care and non-palliative-care settings. Clinicians should remain vigilant for mood complications, not just depression. Funding None.
Platelet-neutrophil interactions are important for innate immunity, but also contribute to the pathogenesis of deep vein thrombosis, myocardial infarction and stroke. Here we report that, under flow, ...von Willebrand factor/glycoprotein Ibα-dependent platelet ‘priming’ induces integrin α
IIb
β
3
activation that, in turn, mediates neutrophil and T-cell binding. Binding of platelet α
IIb
β
3
to SLC44A2 on neutrophils leads to mechanosensitive-dependent production of highly prothrombotic neutrophil extracellular traps. A polymorphism in
SLC44A2
(rs2288904-A) present in 22% of the population causes an R154Q substitution in an extracellular loop of SLC44A2 that is protective against venous thrombosis results in severely impaired binding to both activated α
IIb
β
3
and VWF-primed platelets. This was confirmed using neutrophils homozygous for the
SLC44A2
R154Q polymorphism. Taken together, these data reveal a previously unreported mode of platelet-neutrophil crosstalk, mechanosensitive NET production, and provide mechanistic insight into the protective effect of the
SLC44A2
rs2288904-A polymorphism in venous thrombosis.
Platelets in our blood form clots over sites of injury to stop us from bleeding. Blood clots can also occur in places where they are not needed, such as deep veins in our legs or other regions of the body. Developing such clots – also known as deep vein thrombosis (or DVT for short) – is one of the most common cardiovascular diseases and a major cause of death. Although certain inherited factors have been linked to DVT, the underlying mechanisms of the disease remain poorly understood.
In addition to platelets, the pathological (or dangerous) clots that cause DVT also contain immune cells called neutrophils which fight off bacterial infections. Platelets are recruited to the wall of the vein by a protein called “von Willebrand Factor” (or VWF for short). However, it remained unclear how these recruited platelets interact with neutrophils and whether this promotes the onset of DVT.
To answer this question, Constantinescu-Bercu et al. used a device that mimics the flow of blood to study how human platelets change when they are exposed to VWF. This revealed that VWF ‘primes’ the platelets to interact with neutrophils via a protein called integrin α
IIb
β
3
. Further experiments showed that integrin α
IIb
β
3
binds to a protein on the surface of neutrophils called SLC44A2. Once the neutrophils interacted with the ‘primed’ platelets, they started making traps which increased the size of the blood clot by capturing other blood cells and proteins.
Finally, Constantinescu-Bercu et al. studied a genetic variant of the SLC44A2 protein which is found in 22% of people and is associated with a lower risk of developing DVT. This genetic mutation caused SLC44A2 to interact with ‘primed’ platelets more weakly, which may explain why people with this genetic variant are protected from getting DVT.
These findings suggest that blocking the interaction between ‘primed’ platelets and neutrophils could reduce the risk of DVT. Although current treatments for DVT can prevent patients from forming dangerous blood clots, they can also cause severe bleeding. Since neutrophils are not crucial for normal blood clots to form at the site of injury, drugs targeting SLC44A2 could inhibit inappropriate clotting without causing excess bleeding.
With cancer incidence increasing over time, attention to the burden of related psychiatric and psychosocial consequences of the disease and treatment is a major topic for both cancer patients and ...their caregivers. Among cancer patients, psychiatric (e.g. adjustment, anxiety, depressive disorders) and neuropsychiatric disorders (e.g. cognitive disorders secondary to treatment, delirium) have been shown to affect an average of 30-35% patients, with differences according to stage and type of cancer. Also other psychosocial syndromes (e.g. demoralization, health anxiety, irritable mood) not taken into account in usual nosological systems should be considered for their impact on the patient's quality-of-life. Also, it has been repeatedly reported that psychological distress reverberates substantially throughout the nuclear family, and that a family approach is necessary in cancer care, with the caregiver-patient dyad as a unit to be the focus and direction of assessment and intervention. In this review the most significant psychosocial disorders causing burden for cancer patients and their caregivers are examined, and the main methods of assessment for more proper referral and treatment are summarized.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK ...Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we provide evidence of shared genetic pathways linking blood cell indices with complex pathologies, including autoimmune diseases, schizophrenia, and coronary heart disease and evidence suggesting previously reported population associations between blood cell indices and cardiovascular disease may be non-causal.
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•Genome-wide association study interrogates 36 traits across the hematopoietic system•A total of 2,706 associated variants, including 130 rare and 230 low frequency•Describes allelic spectrum and heritability of coding and regulatory variants•Unravels causal contributions to cardiovascular, immune, and psychiatric disease
As part of the IHEC Consortium, this study probes the allelic architecture and regulatory landscape of cellular complex traits with power to identify causal pathways and links to diseases such as schizophrenia. Explore the Cell Press IHEC web portal at http://www.cell.com/consortium/IHEC.
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