Natural resistance to cancer: A window of hope.

As healthcare systems are improving and thereby the life expectancy of human populations is increasing, cancer is representing itself as the second leading cause of death. Although cancer biologists have put enormous effort on cancer research so far, we still have a long way to go before being able to treat cancers efficiently. One interesting approach in cancer biology is to learn from natural resistance and/or predisposition to cancer. Cancer-resistant species and tissues are thought-provoking models whose study shed light on the inherent cancer resistance mechanisms that arose during the course of evolution. On the other hand, there are some syndromes and factors that increase the risk of cancer development, and revealing their underlying mechanisms will increase our knowledge about the process of cancer formation. Here, we review natural resistance and predisposition to cancer and the known mechanisms at play. Further insights from these natural phenomena will help design future cancer research and could ultimately lead to the development of novel cancer therapeutic strategies.

Definitive aetiology of unexplained syncope after cardiovascular autonomic tests in a tertiary syncope unit.

AIMS: Syncope is a common condition with many possible causes, ranging from benign to life-threatening aetiologies. Establishing a diagnosis can be difficult, and specialized syncope units, using cardiovascular autonomic tests (CATs), including a head-up tilt test, can increase the diagnostic yield. However, up to one-fifth of examined patients have inconclusive CAT results. The aim of the present study was to investigate the predictive value of history, and clinical findings for unexplained syncope after CAT and characterize the group with negative results. METHODS AND RESULTS: Consecutive syncope patients [n = 2663, 61% women, median age 52 (32-69) years] were evaluated and CAT explained aetiology of syncope in 79% of cases, whereas 21% remained unexplained. Predictors of negative CAT were older age at first syncope (+8% higher odds per 10-year increment, P = 0.042), higher supine heart rate (HR; +12% per 10 b.p.m.; P = 0.003), absence of prodromes (+48%; P < 0.001), hypertension (+45%; P = 0.003), diabetes (+82%; P < 0.001), heart failure (+98%; P = 0.014), and coronary artery disease (+51%; P = 0.027). Compared with vasovagal syncope, patients with negative CAT were older, reported more often the absence of prodromes, and had a higher burden of cardiovascular comorbidities. CONCLUSION: A cardiovascular autonomic test established the cause of syncope in 79% of patients evaluated in a syncope unit. Syncope without prodromes and cardiovascular comorbidities were significant predictors of failure to reveal an aetiology from assessment by CAT. These are known risk factors for cardiac syncope and patients with inconclusive CAT warrant further investigation.

Conditioned media from human pluripotent stem cell-derived cardiomyocytes inhibit the growth and migration of lung cancer cells.

Conditioned media (CM) from various cell types contain significant levels of paracrine factors. Recently, therapeutic properties of CM derived from stem cells have been revealed. Based on the fact that heart cancer is extremely rarely, we hypothesized that the CM obtained from human pluripotent stem cell-derived cardiomyocytes might inhibit cancer cell growth and survival. To this end, lung cancer cell line A549 along with human foreskin fibroblasts (HFF) were treated with serial concentrations of cardiomyocyte CM (CCM) or fibroblast CM (FCM). We found that CCM markedly reduced the viability of lung cancer cells, while FCM did not compromise the viability of neither cancer cells nor HFF cells. Furthermore, we determined an optimized CCM concentration, 30 mg/mL, at which the growth, clonogenicity, and migration of A549 and Calu6 lung cancer cell lines were substantially impaired, whereas FCM did not influence these properties. Moreover, lung cancer cells exhibited cell cycle regulation upon treatment with CCM and the rate of apoptosis was markedly increased by cardiomyocyte CM in both lung cancer cell lines tested. Finally, in response to CCM treatment, A549 and Calu6 cells expressed lower levels of antiapoptotic and stemness genes, but higher levels of proapoptotic genes. In conclusion, this study provides cellular and molecular evidence for the antitumor ability of secretome obtained from stem cell-derived cardiomyocytes.

The Influence of Age on Cerebral Tissue Oxygenation in Vasovagal Syncope and Orthostatic Hypotension.

Age-related physiological impairment increases susceptibility to syncope. We tested the hypotheses that cerebral oxygenation during orthostatic provocation, as well as the level at which syncope occurs, differs according to age. Non-invasive hemodynamic monitoring and cerebral oximetry were applied during a head-up tilt test in 139 patients with vasovagal syncope (mean (SD) 45, (17) years, 60%-female); 121 patients with orthostatic hypotension (61.4 (19.2) years, 49.6%-female); and 82 patients with a negative head-up tilt test (45 (18) years, 61%-female). Group differences in cerebral tissue oxygenation levels and systolic blood pressure were assessed in supine at 3 and 10 min of orthostatic provocation, 30 s before (i.e., presyncopal phase) and during syncope in age groups of <30, 30−60, and >60 years. During the head-up tilt test, cerebral tissue oxygenation at the presyncopal phase decreased with age, both in patients with vasovagal syncope (<30 years: 66.9 ± 6.2, 30−60: 64.5 ± 6.1, >60: 62.2 ± 5.8%; p = 0.009) and orthostatic hypotension (<30: 67.4 ± 4.4, 30−60: 61.6 ± 6.2, >60: 57.5 ± 3.9; p < 0.001). Mean systolic blood pressure at the presyncopal phase did not differ according to age. Cerebral oxygenation prior to syncope in older individuals with vasovagal syncope and orthostatic hypotension is lower compared with younger individuals independently of systolic blood pressure. This suggests that the level of cerebral oxygenation at which syncope is elected is lower in older individuals.

Prevention and control of non-communicable diseases in iran: the case for Investment.

BACKGROUND: Non-communicable diseases are imposing a considerable burden on Iran. This study aims to assess the Return on Investment (ROI) for implementation of Non-communicable diseases (NCDs) prevention program in Iran. METHODS: Four disease groups including cardiovascular diseases, diabetes, cancer, and respiratory diseases were included in our ROI analysis. The study followed four steps: 1) Estimating the total economic burden of NCDs using the Cost-of-Illness approach. 2) Estimating the total costs of implementing clinical and preventive interventions using an ingredient based costing at delivering level and a program costing method at central level.3) Calculating health impacts and economic benefits of interventions using the impact measures of avoided incidence, avoided mortality, healthy life years (HLYs) gained, and avoided direct treatment costs. 4) Calculating the ROI for each intervention in 5- and 15- year time horizons. RESULTS: The total economic burden of NCDs to the Iranian economy was IRR 838.49 trillion per year (2018), which was equivalent to 5% of the country's annual Gross Domestic Product (GDP). The package of NCD will lead to 549 000 deaths averted and 2 370 000 healthy life years gained over 15 years, and, financially, Iranian economy will gain IRR 542.22 trillion over 15 years. The highest ROI was observed for the package of physical activity interventions, followed by the interventions addressing salt, tobacco package and clinical interventions. Conclusions NCDs in Iran are causing a surge in health care costs and are contributing to reduced productivity. Those actions to prevent NCDs in Iran, as well as yielding to a notable health impact, are giving a good economic return to the society. This study underscores an essential need for establishment of a national multi-sectorial NCD coordination mechanism to bring together and strengthen existing cross-agency initiatives on NCDs.

Early and late-onset syncope: insight into mechanisms.

AIMS: Unexplained syncope is an important clinical challenge. The influence of age at first syncope on the final syncope diagnosis is not well studied. METHODS AND RESULTS: Consecutive head-up tilt patients (n = 1928) evaluated for unexplained syncope were stratified into age groups <30, 30-59, and ≥60 years based on age at first syncope. Clinical characteristics and final syncope diagnosis were analysed in relation to age at first syncope and age at investigation. The age at first syncope had a bimodal distribution with peaks at 15 and 70 years. Prodromes (64 vs. 26%, P < 0.001) and vasovagal syncope (VVS, 59 vs. 19%, P < 0.001) were more common in early-onset (<30 years) compared with late-onset (≥60 years) syncope. Orthostatic hypotension (OH, 3 vs. 23%, P < 0.001), carotid sinus syndrome (CSS, 0.6 vs. 9%, P < 0.001), and complex syncope (>1 concurrent diagnosis; 14 vs. 26%, P < 0.001) were more common in late-onset syncope. In patients aged ≥60 years, 12% had early-onset and 70% had late-onset syncope; older age at first syncope was associated with higher odds of OH (+31% per 10-year increase, P < 0.001) and CSS (+26%, P = 0.004). Younger age at first syncope was associated with the presence of prodromes (+23%, P < 0.001) and the diagnoses of VVS (+22%, P < 0.001) and complex syncope (+9%, P = 0.018). CONCLUSION: In patients with unexplained syncope, first-ever syncope incidence has a bimodal lifetime pattern with peaks at 15 and 70 years. The majority of older patients present only recent syncope; OH and CSS are more common in this group. In patients with early-onset syncope, prodromes, VVS, and complex syncope are more common.

A multi-centre survey on hospital malnutrition: result of PNSI study.

BACKGROUND: Disease-related malnutrition is associated with adverse outcomes such as increased rates of morbidity and mortality, prolonged hospital stay, and extra costs of health care. This study was conducted to assess nutritional status among patients and to determine the risk factors for malnutrition in Iran university f. METHODS: Persian Nutritional Survey In Hospitals (PNSI) was a cross-sectional study that conducted in 20 university hospitals across Iran. All the patients with age range of 18 to 65 years, who were admitted or discharged, were assessed by subjective global assessment (SGA). RESULTS: In total, 2109 patients were evaluated for malnutrition. Mean values of age and body mass index were 44.68 ± 14.65 years and 25.44 ± 6.25 kg/m2, respectively. Malnutrition (SGA-B & C) was identified in 23.92% of the patients, 26.23 and 21% of whom were among the admitted and discharged patients, respectively. The highest prevalence of malnutrition was in burns (77.70%) and heart surgery (57.84%) patients. Multivariate analysis presented male gender (OR = 1.02, P < 0.00), malignant disease (OR = 1.40, P < 0.00), length of hospital stay (OR = 1.20, P < 0.00), and polypharmacy (OR = 1.06, P < 0.00) as independent risk factors for malnutrition. Malnutrition was not associated with age (P = 0.10). CONCLUSION: This study provides an overall and comprehensive illustration of hospital malnutrition in Iran university hospitals, finding that one out of four patients were malnourished; thus, appropriate consideration and measures should be taken to this issue.

Underlying hemodynamic differences are associated with responses to tilt testing.

Aim of this study was to explore whether differences in resting hemodynamic parameters may be associated with tilt test results in unexplained syncope. We analyzed age, gender, systolic (SBP), diastolic blood pressure (DBP) and heart rate (HR) by merging three large databases of patients considered likely to be of vasovagal reflex etiology, comparing patients who had tilt-induced reflex response with those who did not. Tilt-induced reflex response was defined as spontaneous symptom reproduction with characteristic hypotension and bradycardia. Relationship of demographics and baseline supine BP to tilt-test were assessed using logistic regression models. Individual records of 5236 patients (45% males; mean age: 60 ± 22 years; 32% prescribed antihypertensive therapy) were analyzed. Tilt-positive (n = 3129, 60%) vs tilt-negative patients had lower SBP (127.2 ± 17.9 vs 129.7 ± 18.0 mmHg, p < 0.001), DBP (76.2 ± 11.5 vs 77.7 ± 11.7 mmHg, p < 0.001) and HR (68.0 ± 11.5 vs 70.5 ± 12.5 bpm, p < 0.001). In multivariable analyses, tilt-test positivity was independently associated with younger age (Odds ratio (OR) per 10 years:1.04; 95% confidence interval (CI), 1.01-1.07, p = 0.014), SBP ≤ 128 mmHg (OR:1.27; 95%CI, 1.11-1.44, p < 0.001), HR ≤ 69 bpm (OR:1.32; 95%CI, 1.17-1.50, p < 0.001), and absence of hypertension (OR:1.58; 95%CI, 1.38-1.81, p < 0.001). In conclusion, among patients with suspected reflex syncope, younger age, lower blood pressure and lower heart rate are associated with positive tilt-test result.

Age-related tilt test responses in patients with suspected reflex syncope.

AIMS: Tilt testing (TT) is recognized to be a valuable contribution to the diagnosis and the pathophysiology of vasovagal syncope (VVS). This study aimed to assess the influence of age on TT responses by examination of a large patient cohort. METHODS AND RESULTS: Retrospective data from three experienced European Syncope Units were merged to include 5236 patients investigated for suspected VVS by the Italian TT protocol. Tilt testing-positivity rates and haemodynamics were analysed across age-decade subgroups. Of 5236 investigated patients, 3129 (60%) had a positive TT. Cardioinhibitory responses accounted for 16.5% of positive tests and were more common in younger patients, decreasing from the age of 50-59 years. Vasodepressor (VD) responses accounted for 24.4% of positive tests and prevailed in older patients, starting from the age of 50-59. Mixed responses (59.1% of cases) declined slightly with increasing age. Overall, TT positivity showed a similar age-related trend (P = 0.0001) and was significantly related to baseline systolic blood pressure (P < 0.001). Tilt testing was positive during passive phase in 18% and during nitroglycerine (TNG)-potentiated phase in 82% of cases. Positivity rate of passive phase declined with age (P = 0.001), whereas positivity rate during TNG remained quite stable. The prevalence of cardioinhibitory and VD responses was similar during passive and TNG-potentiated TT, when age-adjusted. CONCLUSIONS: Age significantly impacts the haemodynamic pattern of TT responses, starting from the age of 50. Conversely, TT phase-passive or TNG-potentiated-does not significantly influence the type of response, when age-adjusted. Vagal hyperactivity dominates in younger patients, older patients show tendency to vasodepression.

Shiga toxin-producing bacteria as emerging enteric pathogens associated with outbreaks of foodborne illness in the Islamic Republic of Iran.

BACKGROUND: Detection of the cause of diarrhoeal diseases is important for the management of the outbreaks. AIMS: This study investigated the prevalence of Shiga toxin-producing bacteria in stool samples of patients with diarrhoea associated with outbreaks of foodborne illness in the Islamic Republic of Iran. METHODS: A total of 532 stool and rectal swab samples from 70 sporadic outbreaks during May 2014 to August 2015 were examined for infection with Shiga toxin-producing bacteria. The isolates were examined for carriage of the virulence genes stx1 and stx2 in all isolates and eae/ehxA in Escherichia coli. RESULTS: E. coli, Shigella spp., Citrobacter spp., Enterobacter spp., Klebsiella spp. and other enteric bacteria were detected in 77.7% (376/484), 5.0% (24/484), 3.9% (19/484), 0.4% (2/484), 3.7% (18/484) and 9.3% (45/484) of the samples respectively. Of the 196 sorbitol-negative E. coli strains, 3 (1.5%) carried the stx1 gene as did 2 of the 19 (10.5%) Citrobacter strains. CONCLUSION: Shiga toxin-producing Citrobacter spp. strains should be considered as a newly emerging foodborne pathogen in outbreaks.

Classical and Delayed Orthostatic Hypotension in Patients With Unexplained Syncope and Severe Orthostatic Intolerance.

Background: Orthostatic hypotension (OH) is a major sign of cardiovascular autonomic failure leading to orthostatic intolerance and syncope. Orthostatic hypotension is traditionally divided into classical OH (cOH) and delayed OH (dOH), but the differences between the two variants are not well-studied. We performed a systematic clinical and neuroendocrine characterization of OH patients in a tertiary syncope unit. Methods: Among 2,167 consecutive patients (1,316 women, 60.7%; age, 52.6 ± 21.0 years) evaluated for unexplained syncope and severe orthostatic intolerance with standardized cardiovascular autonomic tests including head-up tilt (HUT), we identified those with a definitive diagnosis of cOH and dOH. We analyzed patients' history, clinical characteristics, hemodynamic variables, and plasma levels of epinephrine, norepinephrine, C-terminal-pro-arginine-vasopressin (CT-proAVP), C-terminal-endothelin-1, mid-regional-fragment of pro-atrial-natriuretic-peptide and pro-adrenomedullin in the supine position and at 3-min HUT. Results: We identified 248 cOH and 336 dOH patients (27% of the entire cohort); 111 cOH and 152 dOH had blood samples collected in the supine position and at 3-min HUT. Compared with dOH, cOH patients were older (68 vs. 60 years, p < 0.001), more often male (56.9 vs. 39.6%, p < 0.001), had higher systolic blood pressure (141 vs. 137 mmHg, p = 0.05), had lower estimated glomerular filtration rate (73 vs. 80 ml/min/1.73 m2, p = 0.003), more often pathologic Valsalva maneuver (86 vs. 49 patients, p < 0.001), pacemaker-treated arrhythmia (5 vs. 2%, p = 0.04), Parkinson's disease (5 vs. 1%, p = 0.008) and reported less palpitations before syncope (16 vs. 29%, p = 0.001). Supine and standing levels of CT-proAVP were higher in cOH (p = 0.022 and p < 0.001, respectively), whereas standing norepinephrine was higher in dOH (p = 0.001). After 3-min HUT, increases in epinephrine (p < 0.001) and CT-proAVP (p = 0.001) were greater in cOH, whereas norepinephrine increased more in dOH (p = 0.045). Conclusions: One-quarter of patients with unexplained syncope and severe orthostatic intolerance present orthostatic hypotension. Classical OH patients are older, more often have supine hypertension, pathologic Valsalva maneuver, Parkinson's disease, pacemaker-treated arrhythmia, and lower glomerular filtration rate. Classical OH is associated with increased vasopressin and epinephrine during HUT, but blunted increase in norepinephrine.

Impact of Cardiovascular Neurohormones on Onset of Vasovagal Syncope Induced by Head-up Tilt.

Background Vasovagal reflex is the most common form of syncope, but the pathophysiological mechanisms that initiate the reflex are not well understood. We aimed to study supine and early orthostatic levels of the neurohormones involved in control of circulatory homeostasis in relation to the onset of tilt-induced vasovagal syncope (VVS). Methods and Results A total of 827 patients who were investigated for unexplained syncope with head-up tilt test (HUT) and optional nitroglycerin provocation (Italian protocol) had blood samples collected while supine and after 3-minutes of HUT. Of these, 173 (20.9%) patients developed VVS during drug-free HUT, 161 of whom (males 44.7%; age 45±21 years) had complete data. We analyzed levels of epinephrine, norepinephrine, C-terminal pro-arginine vasopressin, C-terminal endothelin-1, and midregional fragments of pro-atrial natriuretic peptide and pro-adrenomedullin in relation to time from tilt-up to onset of VVS. We applied a linear regression model adjusted for age and sex. The mean time to syncope was 11±7 minutes. Older age (ß=0.13; SE=0.03, P<0.001), higher supine systolic blood pressure (ß=0.06; SE=0.03, P=0.02), and higher supine midregional fragment of pro-adrenomedullin predicted longer time to syncope (ß=2.31; SE=0.77, P=0.003), whereas supine levels of other neurohormones were not associated with time to syncope. Among 151 patients who developed VVS later than 3 minutes of HUT, increase in epinephrine (ß=-3.24; SE=0.78, P<0.001) and C-terminal pro-arginine vasopressin (ß=-2.07; SE=0.61, P=0.001) at 3 minutes of HUT were related to shorter time to syncope. Conclusions Older age, higher blood pressure, and higher level of pro-adrenomedullin are associated with later onset of VVS during tilt testing, whereas greater increase of tilt-induced epinephrine and vasopressin release correlate with shorter time to syncope.

Malnutrition and medical nutrition therapy in hospitalized children: a case study of using national malnutrition screening tools in northeastern Iran.

BACKGROUND: Nationwide studies have focused only on prevalence of malnutrition in hospitalized children, while medical nutrition therapies and assessing nutritional interventions is neglected. METHODS: This research was conducted in tertiary level children hospitals in the NorthEastern region of Iran for 1 year from 2016 to 2017. Five questions were included in the initial assessment form and, if there was even one positive response, nutritional interventions were prescribed for the patients. RESULTS: A total of 65 children aged ≥ 5 years and hospitalized for ≥ two days were included. 24.6% of patients had 2 >BMI Z-score>-2 at time of admission. At the beginning of the study, weight loss more than 10%, and appetite loss or decreased food intake was observed in 10.8% and 20% of the study population, respectively. Median BMI percentile of patients with nutritional intervention was 8.9 (0.1-98.7) at the beginning of the study and 12.7 (0.1-98.4) at discharge time which shows a significant difference (P=0.01). CONCLUSION: Medical nutrition therapy employed in this study prevented deterioration of nutritional status of children during hospitalization and was effective in stabilizing indices of nutritional status.

The frequency of bacterial contamination and diversity of drug resistance patterns in devices and staff of endoscopy and colonoscopy units.

Background: This study aimed at analyzing microbial contamination in medical equipment, environment, and staff of a gastroenterology unit. Methods: Samples of gastrointestinal imaging devices, the environment, and staff were collected using standard swab-rinse technique and biochemical or molecular characteristics of the isolates, their susceptibility to antibiotics, and similarity of the resistance patterns were investigated. Results: Out of 107 samples, bacterial contamination was detected in the hands of staff (54.1%), imaging devices (56.7%), and in the environment (54.5%). While Pseudomonas spp. were detected only in the imaging devices (13.5%), Bacillus spp. (32.4% and 31.5%), Enterococcus spp. (14.3% and 5.9%), Clostridium difficile (10.8% and 10.5%), and Staphylococcus epidermidis (5.4% and 15.9%) were orderly the most common isolates from samples of the imaging devices and the environment. Nearly, 40% of P. aeruginosa strains were resistant to cefepime, while resistance to cephalosporins and ß-lactamase inhibitor was detected in 33% and 75% of S. aureus strains, respectively. Homology of resistance patterns was detected between the imaging devices and hands of the staff. Conclusion: Our results proposed biofilm and spore forming bacteria as main contaminants of imaging devices in this hospital. Homology of the resistance patterns proposed involvement of staff in contamination of the equipment.

Frequency of Clostridium difficile among patients with gastrointestinal complaints.

AIM: In this study, the prevalence of C. difficile, from patients with gastrointestinal complaints and its association with other enteropathogen microbes were investigated. BACKGROUND: Clostridium difficile is an important pathogen associated with outbreaks of pseudomembranous colitis and other intestinal disorders, such as diarrhea. PATIENTS AND METHODS: Enterotoxin and cytotoxin (toxin A and toxin B) of C. difficile on the patient's stool samples were detected by a double sandwich enzyme-linked Immunosorbant assay technique using a commercial kit (Premier toxins A & B; Generic Assays, Inc., Germany). The microbial isolation and examination was done, according to the standard identification methods. RESULTS: Out of 356 individuals (57.6% male and 42.4% female) the results of C. difficile were positive for 19 patients (5.3%) and negative for 337 patients (94.6%) according to the results of C. difficile antigen kit. There was no association between the existence of C. difficile toxin and microbial population or antibiotic usage. CONCLUSION: This prevalence study clearly supports the hypothesis of a probable role of C.difficile in developing gastrointestinal complaints in patients with diarrhea. More studies are needed to evaluate the role of C. difficile in these diseases.