Changes in Sexuality and Sexual Dysfunction over Time in the First Two Years after Treatment of Head and Neck Cancer

The aim of this study was to investigate changes in sexuality and sexual dysfunction in head and neck cancer (HNC) patients in the first two years after treatment, in relation to the type of treatment. Data were used of 588 HNC patients participating in the prospective NETherlands Quality of life and Biomedical Cohort Study (NET-QUBIC) from diagnosis to 3, 6, 12 and 24 months after treatment. Primary outcome measures were the International Index of Erectile Function (IIEF) and the Female Sexual Function Index (FSFI). The total scores of the IIEF and FSFI were dichotomized into sexual (dys)function. In men, type of treatment was significantly associated with change in erectile function, orgasm, satisfaction with intercourse, and overall satisfaction. In women, type of treatment was significantly associated with change in desire, arousal, and orgasm. There were significant differences between treatment groups in change in dysfunctional sexuality. A deterioration in sexuality and sexual dysfunction from baseline to 3 months after treatment was observed especially in patients treated with chemoradiation. Changes in sexuality and sexual dysfunction in HNC patients were related to treatment, with an acute negative effect of chemoradiation. This effect on the various domains of sexuality seems to differ between men and women.</p

Climate change, reforestation/afforestation, and urbanization impacts on evapotranspiration and streamflow in Europe

Since the 1950s, Europe has undergone large shifts in climate and land cover. Previous assessments of past and future changes in evapotranspiration or streamflow have either focussed on land use/cover or climate contributions or on individual catchments under specific climate conditions, but not on all aspects at larger scales. Here, we aim to understand how decadal changes in climate (e.g. precipitation, temperature) and land use (e.g. deforestation/afforestation, urbanization) have impacted the amount and distribution of water resource availability (both evapotranspiration and streamflow) across Europe since the 1950s. To this end, we simulate the distribution of average evapotranspiration and streamflow at high resolution (1 km²) by combining (a) a steady-state Budyko model for water balance partitioning constrained by long-term (lysimeter) observations across different land use types, (b) a novel decadal high-resolution historical land use reconstruction, and (c) gridded observations of key meteorological variables. The continental-scale patterns in the simulations agree well with coarser-scale observation-based estimates of evapotranspiration and also with observed changes in streamflow from small basins across Europe. We find that strong shifts in the continental-scale patterns of evapotranspiration and streamflow have occurred between the period around 1960 and 2010. In much of central-western Europe, our results show an increase in evapotranspiration of the order of 5 %–15% between 1955–1965 and 2005–2015, whereas much of the Scandinavian peninsula shows increases exceeding 15 %. The Iberian Peninsula and other parts of the Mediterranean show a decrease of the order of 5 %–15 %. A similar north– south gradient was found for changes in streamflow, although changes in central-western Europe were generally small. Strong decreases and increases exceeding 45% were found in parts of the Iberian and Scandinavian peninsulas, respectively. In Sweden, for example, increased precipitation is a larger driver than large-scale reforestation and afforestation, leading to increases in both streamflow and evapotranspiration. In most of the Mediterranean, decreased precipitation combines with increased forest cover and potential evapotranspiration to reduce streamflow. In spite of considerable local- and regional-scale complexity, the response of net actual evapotranspiration to changes in land use, precipitation, and potential evaporation is remarkably uniform across Europe, increasing by ~35–60 km³ yr¯¹, equivalent to the discharge of a large river. For streamflow, effects of changes in precipitation (~95 km³ yr¯¹) dominate land use and potential evapotranspiration contributions (~45–60 km³ yr¯¹). Locally, increased forest cover, forest stand age, and urbanization have led to significant decreases and increases in available streamflow, even in catchments that are considered to be near-natural

The interplay between salmonella and intestinal innate immune cells in chickens

Salmonellosis is a common infection in poultry, which results in huge economic losses in the poultry industry. At the same time, Salmonella infections are a threat to public health, since contaminated poultry products can lead to zoonotic infections. Antibiotics as feed additives have proven to be an effective prophylactic option to control Salmonella infections, but due to resistance issues in humans and animals, the use of antimicrobials in food animals has been banned in Europe. Hence, there is an urgent need to look for alternative strategies that can protect poultry against Salmonella infections. One such alternative could be to strengthen the innate immune system in young chickens in order to prevent early life infections. This can be achieved by administration of immune modulating molecules that target innate immune cells, for example via feed, or by in-ovo applications. We aimed to review the innate immune system in the chicken intestine; the main site of Salmonella entrance, and its responsiveness to Salmonella infection. Identifying the most important players in the innate immune response in the intestine is a first step in designing targeted approaches for immune modulation.The Punjab Educational Endowment Fund, Punjab, Pakistan.https://www.mdpi.com/journal/pathogensam2022Veterinary Tropical Disease

Heat Shock Proteins Can Be Surrogate Autoantigens for Induction of Antigen Specific Therapeutic Tolerance in Rheumatoid Arthritis

Technologies that enable induction of therapeutic tolerance may revolutionize the treatment of autoimmune diseases by their supposed potential to induce drug-free and lasting disease remission. In combination with diagnostic tests that screen for individuals at risk, these approaches may offer chances to halt disease before serious damage in the tissues can occur. In fact, for healthy individuals at risk, this could lead to a preventive form of vaccination. For therapeutic tolerance to re-instate natural self-tolerance it seems essential to induce tolerance for the critical autoantigens involved in disease. However, for most autoimmune diseases such antigens are poorly defined. This is the case for both disease inciting autoantigens and antigens that become involved through epitope spreading. A possible source of surrogate auto-antigens expressed in tissues during inflammation are heat shock proteins (HSP) or stress proteins. In this mini-review we discuss unique characteristics of HSP which provide them with the capacity to inhibit inflammatory processes. Various studies have shown that epitopes of HSP60 and HSP70 molecules can function as vaccines to downregulate a variety of autoimmune inflammatory diseases. Currently, several research groups are developing cell therapies with the intention to reach therapeutic tolerance. In this review, in which we are proposing to ex vivo load tolerant dendritic cells with a Treg inducing HSP70 derived peptide called B29, we are discussing the chances to develop this as an autologous tolDC therapeutic tolerance therapy for rheumatoid arthritis

Perforin and granzyme A release as novel tool to measure NK cell activation in chickens

Natural killer (NK) cells are cytotoxic lymphocytes that are present in the circulation but also in many organs including spleen and gut, where they play an important role in the defense against infections. Interaction of NK cells with target cells leads to degranulation, which results in the release of perforin and granzymes in the direct vicinity of the target cell. Chicken NK cells have many characteristics similar to their mammalian counterparts and based on similarities with studies on human NK cells, surface expression of CD107 was always presumed to correlate with granule release. However, proof of this degranulation or in fact the actual presence of perforin (PFN) and granzyme A (GrA) in chicken NK cells and their release upon activation is lacking. Therefore, the purpose of the present study was to determine the presence of perforin and granzyme A in primary chicken NK cells and to measure their release upon degranulation, as an additional tool to study the function of chicken NK cells. Using human specific antibodies against PFN and GrA in fluorescent and confocal microscopy resulted in staining in chicken NK cells. The presence of PFN and GrA was also confirmed by Western blot analyses and its gene expression by PCR. Stimulation of NK cells with the pectin SPE6 followed by flow cytometry resulted in reduced levels of intracellular PFN and GrA, suggesting release of PFN and GrA. Expression of PFN and GrA reversely correlated with increased surface expression of the lysosomal marker CD107. Finally it was shown that the supernatant of activated NK cells, containing the NK cell granule content including PFN and GrA, was able to kill Escherichia coli. This study correlates PFN and GrA release to activation of chicken NK cells and establishes an additional tool to study activity of cytotoxic lymphocytes in chickens

Changes in supportive care needs over time from diagnosis up to two years after treatment in head and neck cancer patients:A prospective cohort study

Objectives: To investigate changes in supportive care needs (SCNs) over time from diagnosis up to 2 years after treatment among head and neck cancer (HNC) patients, in relation to demographic, personal, clinical, psychological, physical, social, lifestyle, and cancer-related quality of life factors.Materials and methods: Data of the longitudinal NETherlands QUality of Life and Biomedical Cohort study (NET-QUBIC) was used. SCNs were measured using the Supportive Care Needs Survey (SCNS-SF34) and HNC-specific module (SCNS–HNC) before treatment, three, six, 12 and 24 months after treatment. Linear mixed model analyses were used to study SCNs on the physical &amp; daily living (PDL), psychological (PSY), sexuality (SEX), health system, information and patient support (HSIPS), HNC-functioning (HNC-Function), and lifestyle (HNC-Lifestyle) domain, in relation to demographic, personal, clinical, psychological, physical, social, lifestyle, and cancer-related symptoms as measured at baseline.Results: In total, 563 patients were included. SCNs changed significantly over time. At baseline, 65% had ≥1 moderate/high SCN, versus 42.8% at 24 months. Changes in PDL needs were associated with gender, tumor location, smoking, fear of cancer recurrence, oral pain, and appetite loss, changes in PSY with tumor location, fear of recurrence, social support, emotional functioning, physical functioning, coughing, and use of painkillers, changes in SEX with treatment, changes in HSIPS with muscle strength, changes in HNC-Function with tumor stage, location, social support, physical functioning, fatigue, nausea and vomiting, and speech problems, and changes in HNC-Lifestyle with smoking and alcohol use.Conclusion: SCNs diminish over time, but remain prevalent in HNC patients.</p

The course of health-related quality of life in the first 2 years after a diagnosis of head and neck cancer:the role of personal, clinical, psychological, physical, social, lifestyle, disease-related, and biological factors

Purpose: The aim of this prospective cohort study was to estimate the relationship between the course of HRQOL in the first 2 years after diagnosis and treatment of head and neck cancer (HNC) and personal, clinical, psychological, physical, social, lifestyle, HNC-related, and biological factors. Methods: Data were used from 638 HNC patients of the NETherlands QUality of life and BIomedical Cohort study (NET-QUBIC). Linear mixed models were used to investigate factors associated with the course of HRQOL (EORTC QLQ-C30 global quality of life (QL) and summary score (SumSc)) from baseline to 3, 6, 12, and 24 months after treatment. Results: Baseline depressive symptoms, social contacts, and oral pain were significantly associated with the course of QL from baseline to 24 months. Tumor subsite and baseline social eating, stress (hyperarousal), coughing, feeling ill, and IL-10 were associated with the course of SumSc. Post-treatment social contacts and stress (avoidance) were significantly associated with the course of QL from 6 to 24 months, and social contacts and weight loss with the course of SumSc. The course of SumSc from 6 to 24 months was also significantly associated with a change in financial problems, speech problems, weight loss, and shoulder problems between baseline and 6 months. Conclusion: Baseline clinical, psychological, social, lifestyle, HNC-related, and biological factors are associated with the course of HRQOL from baseline to 24 months after treatment. Post-treatment social, lifestyle, and HNC-related factors are associated with the course of HRQOL from 6 to 24 months after treatment.</p

The course of swallowing problems in the first 2 years after diagnosis of head and neck cancer

Introduction: Head and neck cancer (HNC) and its treatment often negatively impact swallowing function. The aim was to investigate the course of patient-reported swallowing problems from diagnosis to 3, 6, 12, and 24 months after treatment, in relation to demographic, clinical, and lifestyle factors. Methods: Data were used of the Netherlands Quality of Life and Biomedical Cohort Study in head and neck cancer research (NET-QUBIC). The primary outcome measures were the subscales of the Swallowing Quality of Life Questionnaire (SWAL-QOL). Linear mixed-effects models (LMM) were conducted to investigate changes over time and associations with patient, clinical, and lifestyle parameters as assessed at baseline. Results: Data were available of 603 patients. There was a significant change over time on all subscales. Before treatment, 53% of patients reported swallowing problems. This number increased to 70% at M3 and decreased to 59% at M6, 50% at M12, and 48% at M24. Swallowing problems (i.e., longer eating duration) were more pronounced in the case of female, current smoking, weight loss prior to treatment, and stage III or IV tumor, and were more prevalent at 3 to 6 months after treatment. Especially patients with an oropharynx and oral cavity tumor, and patients receiving (C)RT following surgery or CRT only showed a longer eating duration after treatment, which did not return to baseline levels. Conclusion: Half of the patients with HNC report swallowing problems before treatment. Eating duration was associated with sex, smoking, weight loss, tumor site and stage, and treatment modality, and was more pronounced 3 to 6 months after treatment

Psychoneurological Symptoms and Biomarkers of Stress and Inflammation in Newly Diagnosed Head and Neck Cancer Patients:A Network Analysis

Psychoneurological symptoms are commonly reported by newly diagnosed head and neck cancer (HNC) patients, yet there is limited research on the associations of these symptoms with biomarkers of stress and inflammation. In this article, pre-treatment data of a multi-center cohort of HNC patients were analyzed using a network analysis to examine connections between symptoms (poor sleep quality, anxiety, depression, fatigue, and oral pain), biomarkers of stress (diurnal cortisol slope), inflammation markers (c-reactive protein [CRP], interleukin [IL]-6, IL-10, and tumor necrosis factor alpha [TNF-α]), and covariates (age and body mass index [BMI]). Three centrality indices were calculated: degree (number of connections), closeness (proximity of a variable to other variables), and betweenness (based on the number of times a variable is located on the shortest path between any pair of other variables). In a sample of 264 patients, poor sleep quality and fatigue had the highest degree index; fatigue and CRP had the highest closeness index; and IL-6 had the highest betweenness index. The model yielded two clusters: a symptoms—cortisol slope—CRP cluster and a IL-6—IL-10—TNF-α—age—BMI cluster. Both clusters were connected most prominently via IL-6. Our findings provide evidence that poor sleep quality, fatigue, CRP, and IL-6 play an important role in the interconnections between psychoneurological symptoms and biomarkers of stress and inflammation in newly diagnosed HNC patients