Health-related quality of life in patients with myalgic encephalomyelitis/chronic fatigue syndrome: an Australian cross-sectional study.

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious and debilitating disorder associated with significant disruptions in daily life including. This study aimed to examine the impact of sociodemographic and patient symptom characteristics on health-related quality of life (HRQoL) of Australians with ME/CFS. METHODS: Self-reported data collected from 480 individuals diagnosed with ME/CFS were obtained between August 2014 and August 2018. This cross-sectional survey analysed sociodemographic, symptom characteristics and HRQoL according to the 36-Item Health Survey (SF-36). Multivariate linear regression models were used to determine ME/CFS symptoms associated with eight domains of HRQoL. RESULTS: Reported HRQoL was significantly impaired in ME/CFS patients across all domains compared with the general population. Scores were the lowest for physical role (4.11 ± 15.07) and energy/fatigue (13.54 ± 13.94). Associations with females, higher body mass index (BMI), employment status, cognitive difficulties, sensory disturbances and cardiovascular symptoms were observed in the physical functioning domain. Impaired pain domain scores were associated with high BMI, annual visits to their general practitioner, flu-like symptoms and fluctuations in body temperature. Reduced well-being scores were associated with smoking status, psychiatric comorbidity, cognitive difficulties, sleep disturbances and gastrointestinal difficulties. CONCLUSION: This study provides evidence that ME/CFS has a profound and negative impact on HRQoL in an Australian cohort.

Roles for endothelial zinc homeostasis in vascular physiology and coronary artery disease.

The discovery of the roles of nitric oxide (NO) in cardiovascular signaling has led to a revolution in the understanding of cardiovascular disease. A new perspective to this story involving zinc (Zn) is emerging. Zn and its associated Zn transporter proteins are important for the integrity and functions of both the large conduit vessels and the microvascular resistance vessels. The Zn and NO pathways are tightly coordinated. Zn ions are required for the dimerization of endothelial nitric oxide synthase and subsequent generation of NO while generation of NO leads to a rapid mobilization of endothelial Zn stores. Labile Zn may mediate important downstream actions of NO including vascular cytoprotection and vasodilation. Several vascular disease risk factors (including aging, smoking and diabetes) interfere with Zn homeostatic mechanisms and both hypozincaemia and Zn transporter protein abnormalities are linked to atherosclerosis and microvascular disease. Some vegetarian diets and long-term use of certain anti-hypertensives may also impact on Zn status. The available evidence supports the existence of a Zn regulatory pathway in the vascular wall that is coupled to the generation and actions of NO and which is compromised in Zn deficiency with consequent implications for the pathogenesis and therapy of vascular disease.

Cardiovascular regulation and body temperature: evidence from a nap vs. sleep deprivation randomized controlled trial.

In this study we set out to understand is sleep fragmentation affects the cardiovascular regulation and circadian variability of core body temperature more or less than sleep deprivation. 50 healthy men (age 29.0+/-3.1 years; BMI 24.3+/-2.1 kg/m(2)) participated in a 3-day study that included one adaptative night and one experimental night involving randomization to: sleep deprivation (SD) and sleep fragmentation (SF). The evaluation included hemodynamic parameters, measures of the spectral analysis of heart rate and blood pressure variability, and the sensitivity of arterial baroreflex function. Core body temperature (CBT) was measured with a telemetric system. SF affects heart rate (61.9+/-5.6 vs. 56.2+/-7.6, p<0.01) and stroke index (52.7+/-11.1 vs. 59.8+/-12.2, p<0.05) with significant changes in the activity of the ANS (LF-sBP: 6.0+/-5.3 vs. 3.4+/-3.7, p<0.05; HF-sBP: 1.8+/-1.8 vs. 1.0+/-0.7, p<0.05; LF-dBP: 5.9+/-4.7 vs. 3.5+/-3.2, p<0.05) more than SD. Post hoc analysis revealed that after SD mean value of CBT from 21:30 to 06:30 was significantly higher compared to normal night's sleep and SF. In healthy men SF affects the hemodynamic and autonomic changes more than SD. Sympathetic overactivity is the proposed underlying mechanism.

Cardiovascular regulation and body temperature: evidence from a nap vs. sleep deprivation randomized controlled trial.

In this study we set out to understand is sleep fragmentation affects the cardiovascular regulation and circadian variability of core body temperature more or less than sleep deprivation. 50 healthy men (age 29.0+/-3.1 years; BMI 24.3+/-2.1 kg/m(2)) participated in a 3-day study that included one adaptative night and one experimental night involving randomization to: sleep deprivation (SD) and sleep fragmentation (SF). The evaluation included hemodynamic parameters, measures of the spectral analysis of heart rate and blood pressure variability, and the sensitivity of arterial baroreflex function. Core body temperature (CBT) was measured with a telemetric system. SF affects heart rate (61.9+/-5.6 vs 56.2+/-7.6, p<0.01) and stroke index (52.7+/-11.1 vs. 59.8+/-12.2, p<0.05) with significant changes in the activity of the ANS (LF-sBP: 6.0+/-5.3 vs. 3.4+/-3.7, p<0.05; HF-sBP: 1.8+/-1.8 vs 1.0+/-0.7, p<0.05; LF-dBP: 5.9+/-4.7 vs. 3.5+/-3.2, p<0.05) more than SD. Post-hoc analysis revealed that after SD mean value of CBT from 21:30 to 06:30 was significantly higher compared to normal night's sleep and SF. In healthy men SF affects the hemodynamic and autonomic changes more than SD. Sympathetic overactivity is the proposed underlying mechanism.

Axitinib versus sorafenib in advanced renal cell carcinoma: subanalyses by prior therapy from a randomised phase III trial.

BACKGROUND: In the AXIS trial, axitinib prolonged progression-free survival (PFS) vs sorafenib in patients with advanced renal cell carcinoma (RCC) previously treated with sunitinib or cytokines. METHODS: In post hoc analyses, patients were grouped by objective response to prior therapy (yes vs no), prior therapy duration (< vs ⩾median), and tumour burden (baseline sum of the longest diameter < vs ⩾median). PFS and overall survival (OS), and safety by type and duration of prior therapy were evaluated. RESULTS: Response to prior therapy did not influence outcome with second-line axitinib or sorafenib. PFS was significantly longer in axitinib-treated patients who received longer prior cytokine treatment and sorafenib-treated patients with smaller tumour burden following sunitinib. Overall survival with the second-line therapy was longer in patients who received longer duration of prior therapy, although not significant in the sunitinib-to-axitinib sequence subgroup; OS was also longer in patients with smaller tumour burden, but not significant in the cytokine-to-axitinib sequence subgroup. Safety profiles differed modestly by type and duration of prior therapy. CONCLUSIONS: AXIS data suggest that longer duration of the first-line therapy generally yields better outcome with the second-line therapy and that lack of response to first-line therapy does not preclude positive clinical outcomes with a second-line vascular endothelial growth factor-targeted agent in patients with advanced RCC.

Radiation sterilization of anthracycline antibiotics in solid state.

The impact of ionizing radiation generated by a beam of electrons of 25-400 kGy on the stability of such analogs of anthracycline antibiotics as daunorubicin (DAU), doxorubicin (DOX), and epidoxorubicin (EPI) was studied. Based on EPR results, it was established that unstable free radicals decay exponentially with the half-time of 4 days in DAU and DOX and 7 days in EPI after irradiation. Radiation-induced structural changes were analyzed with the use of spectrophotometric methods (UV-Vis and IR) and electron microscope imaging (SEM). A chromatographic method (HPLC-DAD) was applied to assess changes in the contents of the analogs in the presence of their impurities. The study showed that the structures of the analogs did not demonstrate any significant alterations at the end of the period necessary for the elimination of unstable free radicals. The separation of main substances and related substances (impurities and potential degradation products) allowed determining that no statistically significant changes in the content of particular active substances occurred and that their conversion due to the presence of free radicals resulting from exposure to an irradiation of 25 kGy (prescribed to ensure sterility) was not observed.

Inflammasome gene expression alterations in Staphylococcus aureus biofilm-associated chronic rhinosinusitis.

BACKGROUND: The role of inflammasomes in chronic inflammation has been the subject of intense research in recent years. Chronic rhinosinusitis (CRS), a persistent inflammatory disease, continues to be investigated hoping that a clearer pathophysiologic description will guide discovery of future treatment modalities. This study investigates the role of inflammasome complexes in CRS patients with Staphylococcus aureus biofilm infection, a key culprit associated with disease severity and recalcitrance. METHODOLOGY: Sinonasal tissue samples were collected from CRS patients with (P+) and without (P-) polyps and controls. S. aureus biofilm status was obtained using fluorescence in situ hybridization and classified as biofilm positive (B+) or negative (B-). RNA was analysed using a Human Inflammasome PCR array, profiling the expression of 84 genes involved in inflammasome function. RESULTS: Sixteen samples were obtained: 5 B+P+, 5 B-P- and 6 controls. Comparing B+P+ vs. controls showed the greatest number of differentially expressed genes. In particular, Absent in Melanoma 2 (AIM2) was consistently and significantly up-regulated in the B+P+ vs. B-P- and controls. In contrast, when comparing the B-P- vs. controls, no genes showed significant changes. CONCLUSION: Our results indicate the involvement of inflammasome complexes and their signalling pathways in CRS patients with polyps and S. aureus biofilms. In particular, AIM2, activated by intracellular double-stranded DNA, is up-regulated in this group, implying that S. aureus may play a role in intracellular triggering of the inflammasome response. Studies with further patient stratification and assessing corresponding protein expression are needed to further characterize the role of inflammasomes in CRS.

Phototherapy with low-level laser influences the proliferation of endothelial cells and vascular endothelial growth factor and transforming growth factor-beta secretion.

The healing process and the angiogenesis associated with it, is a very important but currently poorly understood area. Low level laser therapy (LLLT) has been reported to modulate the process of tissue repair by stimulation of cellular reaction such as migration, proliferation, apoptosis and cellular differentiation. The aim of this work was to evaluate the influence of laser radiation in the range of visible and infrared light on the proliferation of vascular endothelial cells in vitro and the secretion of angiogenic factors: vascular endothelial growth factor (VEGF)-A and transforming growth factor (TGF)-ß. Vascular human endothelial cells (Ecs) were exposed to radiation with laser beam of the wavelengths: 635 nm (1.875 mW/cm²) and 830 nm (3.75 mW/cm²). Depending on the radiation energy density, the experiment was conducted in four groups : I) the control group (no radiation, 0 J/cm²); II) 635 nm - the energy density was 2 J/cm²; III) 635 nm - 4 J/cm²; IV635 nm - 8 J/cm², II) 830 nm - the energy density was 2 J/cm²; III) 830 nm - 4 J/cm²; IV) 830 nm - 8 J/cm². The proliferation and concentration of VEGF-A and TGF-ß were examined. LLLT with wavelength 635 nm increases endothelial cell proliferation. Significant increase in endothelial cell proliferation and corresponding decrease in VEGF concentration may suggest the role for VEGF in this process. The wavelength of 830 nm was associated with a decrease in TGF-ß secretion.

Sicca Symptoms and their Association with Chronic Rhinosinusitis in a Community Sample.

OBJECTIVE: To determine associations between sicca symptoms, chronic rhinosinusitis (CRS) symptoms and asthma in a community survey. METHODS: Data was obtained from the Spring 2009 South Australian Health Omnibus Survey which sampled, via interviewer administered questionnaire, 3007 individuals aged 15 years and over whose socio-demographic distribution corresponded to South Australian population estimates. Respondents were asked a range of questions relating to the presence of persistent dry eyes or dry mouth, CRS and medically diagnosed nasal polyps and asthma. Relationships between symptoms were explored using maximum likelihood dependency tree analysis. RESULTS: THE RESPECTIVE POPULATION PREVALENCES WERE: dry mouth (5.9%), dry eyes (8.6%), nasal polyps (3.8%), CRS (13.2%) and asthma (12.0%). The overall prevalence of sicca symptoms (dry eyes or dry mouth) was 12.4%. Dependency tree analysis revealed the expected symptom clustering between (1) sicca symptoms and their association with female gender and increasing age and (2) CRS, nasal polyps and asthma (one airway hypothesis). However there was also an association between dry eyes and CRS (OR 2.5, 95% CI 1.9, 3.4), which was in fact stronger than the association between CRS and asthma (OR 1.9, 95% CI 1.4, 2.5). CONCLUSIONS: Sicca symptoms are common in the community. Our novel finding of a strong association between dry eyes and CRS suggests that further research into the relationship between airway inflammation and sicca symptoms is required. These findings may have particular relevance to Sjögren's syndrome (SS) in both its primary and secondary forms.

Impaired blood pressure variability in chronic fatigue syndrome--a potential biomarker.

INTRODUCTION: Autonomic dysfunction is common in chronic fatigue syndrome (CFS). This study set out to derive an autonomic biomarker using a comprehensive assessment of heart rate and blood pressure variability. METHODS: Heart rate and non-invasive continuous blood pressure measurements (task force monitor) at rest and on standing were performed in CFS (Fukuda n = 68) and matched controls (n = 68) to derive high frequency (HF; parasympathetic) and low frequency (LF; sympathetic) heart rate variability (HRV), systolic (SBPV) and diastolic (DBPV) blood pressure variability. Variables of significance were combined using receiver operator curves to explore the diagnostic utility of parameters particularly at rest. RESULTS: At rest, LF-HRV (sympathetic) was significantly increased in CFS compared to controls, while parasympathetic markers were significantly reduced (P = 0.006). Total DBP spectral power was increased (P = 0.0003) across all domains, with a shift towards sympathetic and away from parasympathetic SBPV (P = 0.05). On standing, overall SBPV response was significantly reduced with reductions in both sympathetic and parasympathetic components of SBPV (all P < 0.0001). Change in LF-DBP and relative balance of LF/HF DBP on standing differed between CFS and controls (P < 0.0001). Using the 85% sensitivity levels, we determined a threshold for three chosen resting BPV parameters of LF DBP >3.185, rest HF DBP >0.86, rest total DBP >7.05. Achieving all of these differentiated between CFS and controls with 77% sensitivity and 53% specificity. CONCLUSION: This study has shown that there are objectively measured abnormalities of blood pressure variability in CFS and that these abnormalities have the potential to be a bedside diagnostic tool.

Diabetes-linked zinc transporter ZnT8 is a homodimeric protein expressed by distinct rodent endocrine cell types in the pancreas and other glands.

BACKGROUND AND AIMS: Zinc is abundant in pancreas, being required by endocrine islet cells for hormone secretion and by exocrine acinar cells as pancreatic juice component. ZnT8 is a member of the SLC30A family of zinc transporters whose overexpression in cultured pancreatic beta cells leads to increased insulin secretion in response to glucose, suggesting a possible role in regulating glycemia. ZnT8 was therefore proposed as a therapeutic target for diabetes, and recent genome-wide association studies identified polymorphisms in the ZNT8 gene conferring increased type 2 diabetes risk. METHODS AND RESULTS: As limited information was available on the biochemical properties of ZnT8 and on its endogenous expression, we have raised a specific polyclonal antibody and immunostained protein extracts, cell lines and tissue sections. We show that ZnT8 forms a very stable dimer that requires biological membranes to properly assemble. We demonstrate localization of murine ZnT8 to the secretory granules in pancreatic beta and alpha islet cells. Moreover, we show that ZnT8 is also expressed in other secretory cell types, namely the cubical epithelium that lines thyroid follicles and the cortex of the adrenal gland, suggesting a more widespread role in endocrine secretion. CONCLUSION: We provide novel insights into the features of the ZnT8 transporter, of special relevance in light of its proposed role as therapeutical target for diabetes treatment.

Reflex influence of carotid baroreceptor inactivation on respiratory resistance in humans.

Our previous study demonstrated that selective carotid baroreceptors activation decreases airway resistance. The aim of the present study was to evaluate the effect of carotid baroreceptor inactivation on the reflex change of respiratory resistance. Twenty healthy men aged between 20 and 25 were included in the study. Selective inactivation of carotid baroreceptors was induced by generating a positive pressure of 40 mmHg for 5 s in two capsules placed bilaterally on the neck over the bifurcation of the carotid arteries. The oscillatory method (Siregnost FD5, Siemens) was used to measure continuously respiratory resistance. Inactivation of carotid baroreceptors produced a short increase in respiratory resistance by 0.39 +/- 0.01(SE) mbar/l/s, i.e., 21.7% above the resting level. We conclude that in humans, carotid baroreceptors might have a background contribution to bronchodilator tone. This observation seems to be important for clinical situations of impairment of baroreflex function.

Impairment of the baroreflex control of human respiratory resistance with age.

BACKGROUND: The mechanism responsible for the central baroreflex resetting with age are an area of limited knowledge. We previously demonstrated that in subjects aged above 50 the airway resistance did not change in response to baroreceptor activation, whereas in younger volunteers the airway resistance significantly decreased. OBJECTIVE: The aim of the present study was to evaluate the effect of carotid baroreceptor inactivation on the reflex change of respiratory resistance, in the course of aging. MATERIAL AND METHODS: 80 healthy men, divided in four groups: aged 20-30 (Group I), 31-40 (Group II), 41-50 (Group III), and 51-60 (Group IV) were included in the study. The selective inactivation of carotid baroreceptors was induced by generating a positive pressure of 40 mmHg for 5 s in two capsules placed bilaterally on the neck over the bifurcation of the carotid arteries. The oscillatory method (Siregnost FD5, Siemens) was used to measure continuously respiratory resistance. RESULTS: Inactivation of carotid baroreceptors produced a short increase in respiratory resistance by 0.38 +/- 0.01SE mbar/l/s, i.e., 21.7% above the resting level in Group I and by 0.25 +/- 0.01 mbar/l/s in Group II. In the two older groups (III and IV) respiratory resistance did not change in response to baroreceptors inactivation. CONCLUSIONS: In humans aged above 40, carotid baroreceptors do not contribute to bronchodilator tone, which causes imbalance between the activities of upper airway and chest wall inspiratory muscles leading to a collapsing effect on the upper airway.

Apoptosis-regulatory factors as potential drug targets in the epithelium of normal and inflamed airways.

Airway epithelium (AE) lines the conducting airways of the respiratory system and functions to maintain airway integrity by providing both a physical barrier to inhaled noxious agents and a mechanism for their clearance via the mucociliary escalator. Normal AE cells are relatively refractory to a number of apoptotic stimuli and survival mechanisms are in place to maintain the integrity of the epithelial barrier that is exposed to agents such as reactive oxygen species (ROS) and death receptor ligands secreted by immune cells during inflammation. When damage to AE does occur, there is increased AE apoptosis, such as in the airway damage that occurs in the chronically inflamed airways in diseases like asthma where rates of AE apoptosis can be increased many-fold. The usual treatment for persistent asthma in humans involves a combination of bronchodilator and inhaled corticosteroid; there is however a need to develop strategies to better control other aspects of the disease, including minimizing the ongoing damage to AE and consequent airway remodeling. Targeting of the major apoptosis-regulatory factors in AE may be one such strategy. Here we review what is known about apoptosis and its regulatory factors in normal AE and abnormalities in these factors in the inflamed airways of mice and humans.

Zinc and its specific transporters as potential targets in airway disease.

The dietary group IIb metal zinc (Zn) plays essential housekeeping roles in cellular metabolism and gene expression. It regulates a number of cellular processes including mitosis, apoptosis, secretion and signal transduction as well as critical events in physiological processes as diverse as insulin release, T cell cytokine production, wound healing, vision and neurotransmission. Critical to these processes are the mechanisms that regulate Zn homeostasis in cells and tissues. The proteins that control Zn uptake and compartmentalization are rapidly being identified and characterized. Recently, the first images of sub-cellular pools of Zn in airway epithelium have been obtained. This review discusses what we currently know about Zn in the airways, both in the normal and inflamed states, and then considers how we might target Zn metabolism by developing strategies to monitor and manipulate airway Zn levels in airway disease.

Zinc in health and chronic disease.

Zinc is a trace element essential for the optimal function of a variety of biochemical and physiological processes. Its role in healthy aging is particularly important as it prevents neo plastic cell growth, is involved in mitotic cell division, DNA and RNA repair. Although zinc is widely available in food, the daily intake in many persons may be suboptimal. Other causes of low zinc concentrations may be due to small bowel conditions that cause mucosal damage and thus decrease absorption. Chronic diseases associated with alterations in zinc status are bronchial asthma, rheumatoid arthritis and Alzheimer disease. At present it is uncertain if therapy with zinc would assist in the management of these chronic diseases. In view of the important cellular functions of zinc in the human body, a diet with an adequate zinc content is beneficial in promoting healthy aging and maintaining good health.

Quality-of-life benefits and evidence of antitumour activity for patients with brain metastases treated with gefitinib.

Brain metastases are a common complication of non-small-cell lung cancer (NSCLC). The role of chemotherapy in the treatment of brain metastases has not been clearly defined. Emerging case reports of patients with recurrent NSCLC treated as part of the Expanded Access Programme reveal that gefitinib ("Iressa", ZD1839) has clinical activity in some patients with brain metastases. Here, we describe a number of case studies documenting the response of patients with brain metastases to treatment with gefitinib. Many of these patients had quality-of-life benefits with improvement of neurological and systemic symptoms; some had a partial response of their brain metastases and even complete responses have been seen in a few patients. One case report also describes a durable long-term response with concurrent treatment with gefitinib and radiotherapy. Such results call for larger trials designed to evaluate and define the role of gefitinib in the treatment of brain metastases in NSCLC patients, either as a single agent or in combination with radiation therapy.

Histopathological verification of clinical indications to partial inferior turbinectomy.

Surgical treatment in cases where disturbances of the nasal patency causes changes in the nasal inferior turbinates is controversial. The authors performed light- and electron microscopy and morphometric examinations of the mucous membrane of the nasal inferior turbinates obtained after partial inferior turbinectomy in patients with vasomotor and perennial allergic rhinitis and compensation hypertrophy of the nasal inferior turbinate accompanied by nasal deviation of the septum. In specimens obtained from patients with vasomotor rhinitis, a small number of glands and fibrosis of the lamina propria was observed. In specimens obtained from perennial allergic rhinitis patients, plenty of glands and large oedema was observed. In the group with compensatory hypertrophy of the inferior turbinate, normal glands and fibred areas around the vessels were observed. The largest histopathological changes of degeneration and hypertrophy of the nasal mucosa were observed in vasomotor rhinitis patients. Histopathological examination of nasal mucosa slides confirmed the usefulness of a partial inferior turbinectomy, but only in vasomotor rhinitis patients.

Indoor radon concentrations in Poland as determined in short-term (two-day) measurements.

The aim of the present work was to obtain a pattern of 222Rn concentration distributions in typical buildings in Poland. In the investigations, the environmental passive detectors of the PICO-RAD type were used. The study encompassed buildings that were typical for Poland. The distribution of airborne 222Rn concentrations indoors is of a log-normal type. A total 1171 detectors were measured. Measurements were made in 319 basements, the remaining 852 measurements were carried out in the inhabited part of the houses. The radon concentrations in the basements in Bq x m(-3) ranged from 6 to 1300 with the arithmetic mean AM = 60, geometric mean GM = 30 and median M = 28, whereas those in the inhabited parts of the house (above the ground level) were: AM = 25, GM = 17 and M = 16 with the highest record value of 420.

[Tumors of external ear canal. Case reports]. / Guzy przewodu sluchowego zewnetrznego. Opis przypadków.

The authors described two rare cases of tumors of the external auditory meatus. All patients were male 40 and 51 years old. The tumors were removed via external auditory canal approach and extraauricle approach with successful.