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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.

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 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.

Novel platelet and megakaryocyte transcriptome analysis allows prediction of the full or theoretical proteome of a representative human platelet. Here, we integrated the established platelet proteomes from six cohorts of healthy subjects, encompassing 5.2 k proteins, with two novel genome-wide transcriptomes (57.8 k mRNAs). For 14.8 k protein-coding transcripts, we assigned the proteins to 21 UniProt-based classes, based on their preferential intracellular localization and presumed function. This classified transcriptome-proteome profile of platelets revealed: (i) Absence of 37.2 k genome-wide transcripts. (ii) High quantitative similarity of platelet and megakaryocyte transcriptomes (R = 0.75) for 14.8 k protein-coding genes, but not for 3.8 k RNA genes or 1.9 k pseudogenes (R = 0.43–0.54), suggesting redistribution of mRNAs upon platelet shedding from megakaryocytes. (iii) Copy numbers of 3.5 k proteins that were restricted in size by the corresponding transcript levels (iv) Near complete coverage of identified proteins in the relevant transcriptome (log2fpkm > 0.20) except for plasma-derived secretory proteins, pointing to adhesion and uptake of such proteins. (v) Underrepresentation in the identified proteome of nuclear-related, membrane and signaling proteins, as well proteins with low-level transcripts. We then constructed a prediction model, based on protein function, transcript level and (peri)nuclear localization, and calculated the achievable proteome at ~ 10 k proteins. Model validation identified 1.0 k additional proteins in the predicted classes. Network and database analysis revealed the presence of 2.4 k proteins with a possible role in thrombosis and hemostasis, and 138 proteins linked to platelet-related disorders. This genome-wide platelet transcriptome and (non)identified proteome database thus provides a scaffold for discovering the roles of unknown platelet proteins in health and disease.

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. 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. 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. 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. 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.

Purpose of Review We summarized peer-reviewed literature on aggressive episodes perpetrated by adult patients admitted to general hospital units, especially psychiatry or emergency services. We examined the main factors associated with aggressive behaviors in the hospital setting, with a special focus on the European experience. Recent Findings A number of variables, including individual, historical, and contextual variables, are significant risk factors for aggression among hospitalized people. Drug abuse can be considered a trans-dimensional variable which deserves particular attention. Summary Although mental health disorders represent a significant component in the risk of aggression, there are many factors including drug abuse, past history of physically aggressive behavior, childhood abuse, social and cultural patterns, relational factors, and contextual variables that can increase the risk of overt aggressive behavior in the general hospital. This review highlights the need to undertake initiatives aimed to enhance understanding, prevention, and management of violence in general hospital settings across Europe.

The need for new safe and efficacious therapies has led to an increased focus on biologics produced in mammalian cells. The human cell line HEK293 has bio-synthetic potential for human-like production attributes and is currently used for manufacturing of several therapeutic proteins and viral vectors. Despite the increased popularity of this strain we still have limited knowledge on the genetic composition of its derivatives. Here we present a genomic, transcriptomic and metabolic gene analysis of six of the most widely used HEK293 cell lines. Changes in gene copy and expression between industrial progeny cell lines and the original HEK293 were associated with cellular component organization, cell motility and cell adhesion. Changes in gene expression between adherent and suspension derivatives highlighted switching in cholesterol biosynthesis and expression of five key genes (RARG, ID1, ZIC1, LOX and DHRS3), a pattern validated in 63 human adherent or suspension cell lines of other origin.

Background Demoralisation is a clinically significant problem among cancer patients with a prevalence of 13%–18%. It is defined by difficulty in adjusting to a stressor, wherein the person feels trapped in their predicament and experiences helplessness, hopelessness, loss of confidence and loss of meaning in life. Demoralisation has a strong link with the desire for hastened death and suicidal ideation among the medically ill. This study explored whether a group of symptoms could be identified, distinct from depression, but consistent with adjustment difficulties with demoralisation and linked to ideation of death and suicide. Methods Exploratory Graph Analysis, a network psychometrics technique, was conducted on a large German study of 1529 cancer patients. Demoralisation was measured with the Demoralisation Scale II and depressive symptoms with the PHQ‐9. Results A network of symptoms, with four stable communities, was identified: 1. Loss of hope and meaning; 2. Non‐specific emotionality; 3. Entrapment; 4. Depressive symptoms. The first three communities were clearly distinct from the PHQ‐9 depressive symptoms, except for suicidality and fear of failure. Community 1, Loss of hope and meaning, had the strongest association with thoughts of death and suicide. Hopelessness, loss of role in life, tiredness, pointlessness and feeling trapped were the most central symptoms in the network. Conclusions Communities 1 to 3 are consistent with poor coping without anhedonia and other classic depression symptoms, but linked to suicidal ideation. For people facing the existential threat of cancer, this may indicate poor psychological adjustment to the stressors of their illness. Demoralisation is a prevalent and clinically significant problem among cancer patients, more highly associated with suicidal thinking than depression. New psychometric techniques using network analysis provide evidence that demoralisation may be an important element of psychological adjustment, explaining the independent link of adjustment disorder to suicidality and potentially contributing to a more clinically useful conceptualisation of adjustment disorder.