Use of Biomarkers to Objectively Evaluate Pain in Critically Ill Children: A Scoping Review.

BACKGROUND: Many studies have been conducted recently to identify biomarkers that could potentially be used to objectively evaluate pain. OBJECTIVE: To synthesize and critically analyze primary studies of endogenous biomarkers and their associations with pain to identify suitable biomarkers for the objective evaluation of pain in critically ill children. METHODS: PubMed, Scopus, and Ovid databases were searched; searches were restricted by publication date, language, species, and participant age. Critical appraisal tools and the Strengthening the Reporting of Observational Studies in Epidemiology checklist were used to evaluate quality of evidence. RESULTS: All included articles were coded according to methods and findings. Saliva, blood, cerebrospinal fluid, and gingival crevicular fluid were used to detect biomarkers. Enzyme-linked immunosorbent assays were used in most studies (64%). Appropriate statistical analyses were performed at a significance level of P < .05 in included studies. Cytokines, peptides, and hormones were associated with pain, stress, and inflammatory response, suggesting that they can be used to screen for pain in children during painful conditions. Only 1 study in neonates did not show any correlation between saliva biomarkers and pain. CONCLUSION: According to this literature review, various biomarkers that are easily obtained and measured in a clinical setting are associated with pain in children. Further investigation of these biomarkers through observational studies is suggested to evaluate their suitability for pain assessment in critically ill children.

The Total Intra Venous Anesthesia Effect Versus Volatile Anesthesia, on Stress and Pain Levels, in Patients Undergoing Breast Reconstruction in Ambulatory Surgery Center Total Intra Venous Anesthesia Protocol and Stress Response.

AIM: To compare pain and stress response through cortisol and DHEA levels, implementing. Total intra venous anesthesia (TIVA) versus general anesthesia with volatile anesthetics (VOL). DESIGN: This is a prospective randomized correlation study with consecutive measurements. METHODS: In an ambulatory surgical center from October of 2019 to August of 2020, patients who underwent breast reconstruction with autologous fat grafting were randomized into 2 groups. Patients in the TIVA group (n = 23) received intravenous anesthesia and those in the VOL group (n = 23) received volatile anesthesia (desflurane). Demographic, anthropometric and clinical data were recorded. Arterial systolic (SP) and diastolic (DP) blood pressure, heart rate and oxygen saturation were recorded. Pain and stress levels were evaluated through salivary cortisol and DHEA levels at 4 different time points: T0) 1 hour before induction, T1) during the induction, T2) during anesthesia maintenance, and T3) in recovery phase. Statistical analysis was performed with SPSS 25.0 at significant level α = .05. FINDINGS: There were no statistically significant differences between the 2 groups regarding demographic features. Interestingly that there was a statistically significant difference in the vital sign monitoring where patients in the TIVA group reported with higher levels of SP(T2) and DP (T2), whilst DHEA (T1) levels was correlated positively with patient's age and cortisol (T1) levels and negatively with DP (T3). CONCLUSIONS: This study supports the use of TIVA as a safe and effective option for anesthesia in patients undergoing breast reconstruction with autologous fat grafting.

The Role of Substance P, Neurokinin A, Neuropeptide Y, and Cortisol in Assessing Neonatal Pain.

Introduction: Our aim was to investigate biomarkers of neonatal pain and their association with two pain scales. Methods: This prospective study included 54 full-term neonates. Levels of substance P (SubP), neurokinin A (NKA), neuropeptide Y (NPY), and cortisol were recorded and two pain scales (Premature Infant Pain Profile [PIPP] and Neonatal Infant Pain Scale [NIPS]) were used. Results: A statistically significant decrease in the levels of NPY (p = 0.02) and NKA (p = 0.03) was detected. A significant increase in NIPS scale (p < 0.001) and PIPP scale (p < 0.001) postpainful intervention was also detected. There was a positive correlation between cortisol and SubP (p = 0.01), NKA and NPY (p < 0.001) and between NIPS and PIPP (p < 0.001). A negative correlation was found for NPY with SubP (p = 0.004), cortisol (p = 0.02), NIPS (p = 0.001) and PIPP (p = 0.002). Conclusions: Novel biomarkers and pain scales may help in designing an objective tool for the quantification of neonatal pain in the everyday practice.

Suboptimal Serologic Immunity Against Poliomyelitis Among New Migrant Children in Greece Calls for Organized Action.

BACKGROUND: Migration-flows pose the risk of poliovirus reintroduction from endemic countries to Greece. This study aims to evaluate serologic-immunity/vaccination against poliomyelitis in newly-arriving migrant children. METHODS: Demographic-immunisation data and blood-serum were obtained from migrants 1-14years-old, referred to a hospital-clinic in Athens-Greece within three months from arrival. Immunity to polioviruses-1-3 was determined by serum-neutralizing-antibodies(WHO guidelines). Titers ≥ 1:8 were considered positive. RESULTS: From 9/2010 to 9/2013, 274 children(150 refugees/124 immigrants), mean age 7.1years-old, were enrolled. Only 57(20.8%) of them presented with vaccination-records. Children originated mainly from Asia(n = 198), Eastern Europe(n = 28), Middle East(n = 24) and Africa(n = 24) with 160(58.4%) from polio-endemic-countries(Afghanistan-112(40.8%), Pakistan-24(8.8%) and India-24(8.8%)). Seropositivity against polio-1-2&3 was 84.3%, 86.1% and 74.5%, respectively. Immigrants, had higher seroprotective rates against polioviruses-1-2&3 than refugees(polio-1:p = 0.002;polio-2:p = 0.004,polio-3:p < 0.001). Seronegativity to 1PVs-2PVs and all three polio serotypes was found in 37(13.5%),12 (4.4%), and 30 children(10.9%) respectively. Increasing number of vaccine-doses, and younger-age, were positively-associated with seropositivity. DISCUSSION: A remarkable fraction of newly-arrived migrant-children were seronegative to one or more polioviruses.

Gestational exposure to an epidemiologically defined mixture of phthalates leads to gonadal dysfunction in mouse offspring of both sexes.

The increasing concern for the reproductive toxicity of abundantly used phthalates requires reliable tools for exposure risk assessment to mixtures of chemicals, based on real life human exposure and disorder-associated epidemiological evidence. We herein used a mixture of four phthalate monoesters (33% mono-butyl phthalate, 16% mono-benzyl phthalate, 21% mono-ethyl hexyl phthalate, and 30% mono-isononyl phthalate), detected in 1st trimester urine of 194 pregnant women and identified as bad actors for a shorter anogenital distance (AGD) in their baby boys. Mice were treated with 0, 0.26, 2.6 and 13 mg/kg/d of the mixture, corresponding to 0x, 10x, 100x, 500x levels detected in the pregnant women. Adverse outcomes detected in the reproductive system of the offspring in pre-puberty and adulthood included reduced AGD index and gonadal weight, changes in gonadal histology and altered expression of key regulators of gonadal growth and steroidogenesis. Most aberrations were apparent in both sexes, though more pronounced in males, and exhibited a non-monotonic pattern. The phthalate mixture directly affected expression of steroidogenesis as demonstrated in a relevant in vitro model. The detected adversities at exposures close to the levels detected in pregnant women, raise concern on the existing safety limits for early-life human exposures and emphasizes the need for re-evaluation of the exposure risk.

Validation of Greek Versions of the Neonatal Infant Pain Scale and Premature Infant Pain Profile in Neonatal Intensive Care Unit.

BACKGROUND: The Neonatal Infant Pain Scale and the Premature Infant Pain Profile have been used widely in neonatal intensive care units for pain assessment. AIM: This study reports the evaluation and validation of these scales in full-term newborns who were hospitalized in two Greek neonatal intensive care units. Evaluation and validation of the Neonatal Infant Pain Scale and the Premature Infant Pain Profile in full-term newborns who were hospitalized in two Greek neonatal intensive care units. MATERIALS AND METHODS: This is a cross-sectional study. Two neonatal intensive care units at a large General Children's Hospital in Greece. A total of 81 full-term newborns. This cross-sectional study was conducted in two neonatal intensive care units at a large General Children's Hospital in Greece. We studied 81 full-term newborns, who were exposed to various painful routine procedures. A single measurement was taken from each neonate. Two observers were present during each procedure and evaluated pain using both the Neonatal Infant Pain Scale and Premature Infant Pain Profile. Internal consistency coefficient Cronbach's α, internal class agreement coefficient, and κ factor were appropriately measured. RESULTS: The weighting of the Neonatal Infant Pain Scale and Premature Infant Pain Profile pointed out an excellent coherence between the two scales and agreement among the researchers. The internal consistency coefficient Cronbach's α was >.8 and the internal class agreement coefficient was >.98 for both scales, which indicates an excellent consistency between scales. The κ factor for Neonatal Infant Pain Scale was >.73 and for the Premature Infant Pain Profile it was >.6, which indicates a significant agreement among investigators. CONCLUSIONS: The Neonatal Infant Pain Scale and Premature Infant Pain Profile were successfully adjusted in Greek standards with reliability between the scales and among the researchers. Moreover, they constitute reliable tools for the evaluation of neonatal procedural pain in full-term newborns in Greece.

Association between lymphocyte expression of the apoptotic receptor Fas and pain in critically ill patients.

OBJECTIVE: Lymphocyte apoptosis in critical illness is associated with immunosuppression. We explored for the first time the associations between pain ratings and expression of the apoptotic receptor Fas on B and T cells in critically ill patients and the potential mediating effects of adrenocorticotropic hormone (ACTH), cortisol, and substance P (SP). DESIGN: This is an exploratory correlational study with repeated measurements (14 days followup) and cross-sectional comparisons. SETTING: This study was conducted in a state hospital in the metropolitan area of Athens, Greece. PARTICIPANTS: The participants were 36 consecutive critically ill patients and 36 matched controls. OUTCOME MEASURES: Pain measured by the self-reported numeric rating scale [NRS], the behavioral pain scale, and the pain assessment scale was the primary outcome measure. Flow cytometry (Fas), electrochemiluminescence (ACTH and cortisol) and enzyme-linked immunosorbent assay (SP) were used. Mixed linear models for repeated measurements and bivariable associations at discrete time points were employed. RESULTS: Significant pain at rest was noted. Pain ratings associated with Fas expression on cytotoxic T cells (P=0.041) and B cells (P=0.005), even after adjustment for a number of clinical treatment factors (P=0.006 and P=0.052, respectively). On the day that more patients were able to communicate, Fas on B cells (r=0.897, P=0.029) and cytotoxic T cells (r=0.832; P=0.037) associated with NRS ratings. Associations between pain ratings and ACTH serum levels were noted (P<0.05). When stress neuropeptide levels were added to the model, the statistical significance of the associations between pain ratings and Fas expression was attenuated (P=0.052-0.063), suggesting that stress neuropeptides may partially mediate the association. CONCLUSION: Preliminary evidence for the association between pain and lymphocyte apoptotic susceptibility is provided. The role of pain management in maintaining immunocompetence in critical illness is worth exploring.

Comparative Evaluation of Pain, Stress, Neuropeptide Y, ACTH, and Cortisol Levels Between a Conventional Postoperative Care Protocol and a Fast-Track Recovery Program in Patients Undergoing Major Abdominal Surgery.

BACKGROUND: Fast-track (FT) postoperative protocol in oncological patients after major abdominal surgery reduces complications and length of postoperative stay compared to the conventional (CON) protocol. However, stress and pain responses have not been compared between the two protocols. OBJECTIVES: To compare stress, pain, and related neuropeptidic responses (adrenocorticotropic hormone [ACTH], cortisol, and neuropeptide Y [NPY]) between FT and CON protocols. METHOD: A clinical trial with repeated measurements was conducted (May 2012 to May 2014) with a sample of 63 hepatectomized or pancreatectomized patients randomized into two groups: FT ( n = 29) or CON ( n = 34). Demographic and clinical data were collected, and pain (Visual Analog Scale [VAS] and Behavioral Pain Scale [BPS]) and stress responses (3 self-report questions) assessed. NPY, ACTH, and cortisol plasma levels were measured at T1 = day of admission, T2 = day of surgery, and T3 = prior to discharge. RESULTS: ACTHT1 and ACTHT2 levels were positively correlated with self-reported stress levels (ρ = .43 and ρ = .45, respectively, p < .05) in the FT group. NPY levels in the FT group were higher than those in the CON group at all time points ( p ≤ .004); this difference remained significant after adjusting for T1 levels through analysis of covariance for age, gender, and body mass index ( F = .003, F = .149, F = .015, respectively, p > .05). CONCLUSIONS: Neuropeptidic levels were higher in the FT group. Future research should evaluate this association further, as these biomarkers might serve as objective indicators of postoperative pain and stress.

A Randomized Controlled Trial for the Effectiveness of Progressive Muscle Relaxation and Guided Imagery as Anxiety Reducing Interventions in Breast and Prostate Cancer Patients Undergoing Chemotherapy.

Objective. To test the effectiveness of guided imagery (GI) and progressive muscle relaxation (PMR) as stress reducing interventions in patients with prostate and breast cancer who undergo chemotherapy. Methods. Patients were randomly assigned to either the control group or the intervention group (PMR and GI). Patients were observed for a total duration of 3 weeks and assessed with the SAS and BECK-II questionnaires for anxiety and depression, respectively, in addiotion to two biological markers (saliva cortisol and saliva amylase) (trial registration number: NCT01275872). Results. 256 patients were registered and 236 were randomly assigned. In total 104 were randomised to the control group and 104 to the intervention group. Intervention's mean anxiety score and depression score changes were significantly different compared to the control's (b = -29.4, p < 0.001; b = -29.4, p < 0.001, resp.). Intervention group's cortisol levels before the intervention (0.30 ± 0.25) gradually decreased up to week 3 (0.16 ± 0.18), whilst the control group's cortisol levels before the intervention (0.21 ± 0.22) gradually increased up to week 3 (0.44 ± 0.35). The same interaction appears for the Amylase levels (p < 0.001). Conclusions. The findings showed that patients with prostate and breast cancer undergoing chemotherapy treatment can benefit from PMR and GI sessions to reduce their anxiety and depression.

Pilot investigation of the association between serum stress neuropeptide levels and lymphocyte expression of fas and fas ligand in critical illness.

INTRODUCTION: In critical illness, apoptotic loss of immunocytes is associated with immunosuppression. AIM: To explore expression of Fas/Fas ligand (FasL) on B and T cells from critically ill patients without sepsis compared to matched controls and associations with disease severity and neuropeptide Y (NPY), cortisol, adrenocorticotropic hormone (ACTH), and prolactin (PRL) levels. METHODS: Repeated-measures correlational design with 36 critically ill patients (14-day follow-up) and 36 controls. Disease severity was assessed using the Multiple Organ Dysfunction Score (MODS) and Multi Organ Failure scale. Fas/FasL values were standardized for viable cell counts. An enzyme-linked immunosorbent assay (NPY) and electrochemiluminescence immunoassay (cortisol, ACTH, and PRL) were employed. RESULTS: Fas and FasL expression on T-helper (p < .0001-.03) and T-cytotoxic cells (p < .0001-.002) and Fas expression on B cells (p < .0001-.03) were higher in patients. MODS severity was associated with FasL expression on cytotoxic T cells (r = .752-.902, p = .023-.037). There was an inverse association between Day 1 NPY levels and Fas expression on T-helper cells (r = -.447, p = .019). On the day of maximum severity, we report for the first time an inverse association between NPY levels and FasL expression on helper (r = -.733, p = .016) and cytotoxic (r = -.862, p = .003) T cells. Cortisol levels were positively associated with counts of FasL-positive helper (r = .828) and cytotoxic (r = .544, p < .05) T cells. CONCLUSION: Results suggest a potential role for stress neuropeptides in lymphocyte survival and activation in critical illness.

Virus antibody survey in different European populations indicates risk association between coxsackievirus B1 and type 1 diabetes.

Enteroviruses (EVs) have been connected to type 1 diabetes in various studies. The current study evaluates the association between specific EV subtypes and type 1 diabetes by measuring type-specific antibodies against the group B coxsackieviruses (CVBs), which have been linked to diabetes in previous surveys. Altogether, 249 children with newly diagnosed type 1 diabetes and 249 control children matched according to sampling time, sex, age, and country were recruited in Finland, Sweden, England, France, and Greece between 2001 and 2005 (mean age 9 years; 55% male). Antibodies against CVB1 were more frequent among diabetic children than among control children (odds ratio 1.7 [95% CI 1.0-2.9]), whereas other CVB types did not differ between the groups. CVB1-associated risk was not related to HLA genotype, age, or sex. Finnish children had a lower frequency of CVB antibodies than children in other countries. The results support previous studies that suggested an association between CVBs and type 1 diabetes, highlighting the possible role of CVB1 as a diabetogenic virus type.

Altered serum stress neuropeptide levels in critically ill individuals and associations with lymphocyte populations.

OBJECTIVE: Potential physiological correlates of stress and the role of stress neuropeptides, other than those of the hypothalamic-pituitary-adrenal axis, in critical illness have not been addressed. We investigated: (a) serum levels of stress neuropeptides (ACTH, substance P (SP), neuropeptide Y (NPY), cortisol, prolactin) in critically ill individuals compared to matched controls, (b) associations with lymphocyte counts, (c) associations among stress neuropeptide levels, and (d) associations with perceived intensity of stress, critical illness severity and survival. METHODS: Correlational design with repeated measures. Thirty-six critically ill patients were followed up for 14 days compared to 36 healthy matched controls. Stress was assessed by the ICUESS scale. Correlations, cross-sectional comparisons and multiple regression models were pursued. RESULTS: For the first time, we report lower SP (Difference of means (DM) = 2928-3286 ng/ml, p < 0.001) and NPY (DM = 0.77-0.83 ng/ml, p < 0.0001) levels in critically ill individuals compared to controls. Cortisol levels were higher (DM = 140-173 ng/ml, p<0.0001) and lymphocyte population counts (p < 0.002) were lower in patients throughout the study. NPY levels associated with lymphocyte (r = 0.411-0.664, p < 0.04), T-lymphocyte (r = 0.403-0.781, p< 0.05), T-helper (r = 0.492-0.690, p < 0.03) and T-cytotoxic cell populations (r = 0.39-0.740, p < 0.03). On day 1, cortisol levels exhibited associations with lymphocyte (r = -0.452, p = 0.01), T-cell (r = -0.446, p = 0.02), T-helper (r = -0.428, p = 0.026) and T-cytotoxic cells ( r = -0.426, p = 0.027). ACTH levels associated with NK cell counts (r = 0.326-0.441, p < 0.05). Associations among stress neuropeptides levels were observed throughout (p < 0.05). ACTH levels associated with disease severity (r = 0.340-0.387, p < 0.005). A trend for an association between ACTH levels and intensity of stress was noted (r = 0.340, p = 0.057). CONCLUSION: The significantly lowered NPY and SP levels and the associations with cortisol, ACTH and lymphocytes suggest that the role of these peptides in critical illness merit further investigation. Future studies need to address associations between these neuropeptides and functional immune cell responses and inflammatory markers in critical illness.

Seasonal variation of type 1 diabetes mellitus diagnosis in Greek children.

OBJECTIVE: The aim of the study was to investigate the seasonal variation of type 1 diabetes mellitus (T1DM) diagnosis in Greek children. DESIGN: The study group consisted of 1148 patients (604 males and 544 females) who were diagnosed with T1DM during the period 1978-2008. The mean age at diagnosis was 8.32 ± 5.01 years. The date of birth and the date at diagnosis were recorded from the patients' files. RESULTS: Significantly more children were diagnosed with T1DM during the cold months as opposed to the warm months (p=0.001), with no differences between boys and girls. When children were categorized into the age groups ≤ 3 and >3 years old the seasonal variation pattern was different in younger ages suggesting that environmental factors which possibly interfere with T1DM diagnosis may have a different effect in those of younger than older age. With regard to date of birth, significantly more children with diabetes were born during the Spring-Summer than in Autumn-Winter (p=0.004). CONCLUSIONS: The results of the study support the concept of seasonality in T1DM diagnosis, implying a possible relationship between clinical expression of T1DM and various climatic factors. Seasonal variation at diagnosis appears to be different in younger compared to older children.

Potential effects of stress in critical illness through the role of stress neuropeptides.

AIMS AND OBJECTIVES: To critically review evidence on the hypothesis that the multitude of cognitive and psychological stressors perceived by critically ill individuals may contribute to the development of pathophysiologic sequlae through modulation of the levels of stress neuropeptides. BACKGROUND: Critically ill individuals experience high levels of stress and intense adverse emotions. Although psychological stress has long been recognized as a factor in disease, and despite the nursing tenet on the importance of patients' psychological responses, in critical care, the potential physiologic effects of stress have received little attention. DESIGN, METHODS: Narrative critical review. Databases searched included Medline, CINAHL, PubMed and the Cochrane Library. Evidence on the role of stress neuropeptides and pertinent findings in critically ill individuals are reviewed. RESULTS: Limbic and extra-limbic brain structures along with specific stress neuropeptides [corticotrophin releasing hormone (CRH), adrenocorticotropin hormone (ACTH), neuropeptide Y , vasopressin, prolactin, oxytocin, substance P, cholecystokinin, endorphins, enkephalins, somatostatin, noradrenaline, melatonin] are involved in emotional and stress responses. Research evidence indicates that stress neuropeptide levels may be altered in critical illness. Moreover, they mediate processes such as immunity, endothelial response and oxidative stress. A framework for future research and practice is presented. CONCLUSIONS: It is probable that, in critical illness, psychological stress accentuates pathophysiological sequlae, through release of neuropeptides. The role of neuropeptides is suggested as an important field of investigation for critical care nursing. However, currently available data are insufficient to draw firm conclusions. Focussed studies on the physiologic correlates of psychological stress in the critically ill are needed. RELEVANCE TO CLINICAL PRACTICE: If this hypothesis is corroborated, bedside quantification of selected neuropeptides may contribute to the assessment of stress and of the effectiveness of psychological support interventions in the future. Moreover, psychosocial and, probably, pharmacological support interventions may be effective adjuncts to the care of the critically ill.

SMARTDIAB: a communication and information technology approach for the intelligent monitoring, management and follow-up of type 1 diabetes patients.

SMARTDIAB is a platform designed to support the monitoring, management, and treatment of patients with type 1 diabetes mellitus (T1DM), by combining state-of-the-art approaches in the fields of database (DB) technologies, communications, simulation algorithms, and data mining. SMARTDIAB consists mainly of two units: 1) the patient unit (PU); and 2) the patient management unit (PMU), which communicate with each other for data exchange. The PMU can be accessed by the PU through the internet using devices, such as PCs/laptops with direct internet access or mobile phones via a Wi-Fi/General Packet Radio Service access network. The PU consists of an insulin pump for subcutaneous insulin infusion to the patient and a continuous glucose measurement system. The aforementioned devices running a user-friendly application gather patient's related information and transmit it to the PMU. The PMU consists of a diabetes data management system (DDMS), a decision support system (DSS) that provides risk assessment for long-term diabetes complications, and an insulin infusion advisory system (IIAS), which reside on a Web server. The DDMS can be accessed from both medical personnel and patients, with appropriate security access rights and front-end interfaces. The DDMS, apart from being used for data storage/retrieval, provides also advanced tools for the intelligent processing of the patient's data, supporting the physician in decision making, regarding the patient's treatment. The IIAS is used to close the loop between the insulin pump and the continuous glucose monitoring system, by providing the pump with the appropriate insulin infusion rate in order to keep the patient's glucose levels within predefined limits. The pilot version of the SMARTDIAB has already been implemented, while the platform's evaluation in clinical environment is being in progress.

Medical and nursing students with suboptimal protective immunity against vaccine-preventable diseases.

OBJECTIVES: Medical and nursing students (hereafter referred to as "healthcare students") are at risk of contracting and transmitting infectious diseases in a hospital setting. The aim of our study was to evaluate the vaccination history of healthcare students and their serologic immunity against vaccine-preventable diseases. DESIGN: Prospective cohort study. SETTING: A tertiary care children's hospital in Athens, Greece, which is affiliated with the University of Athens. METHODS: Healthcare students were recruited during April through November 2007. The information obtained from these students during personal interviews included demographics and whether there was a history of varicella, measles, mumps, rubella, and/or hepatitis A or B virus infection. Vaccination history and documentation of disease were abstracted from available medical records. Serum antibodies against the above-mentioned viral agents were determined by use of an enzyme-linked immunosorbent assay. Seronegative students and those with immunization gaps were referred to local vaccination clinics, and compliance was assessed 3 months later. RESULTS: A total of 187 healthcare students were recruited, 131 (70.1%) of whom provided complete documentation of vaccination history. Adequate immunity against diphtheria and tetanus was documented for 55 (37.2%) and 73 (49.3%) of the 148 participants, respectively, whereas age-appropriate vaccination against pertussis, diphtheria, tetanus, and poliomyelitis was noted for 138 (93.2%), 147 (99.3%), 147 (99.3%), and 147 (99.3%) healthcare students, respectively. Of 185 healthcare students, 171 (92.4%) were immune to varicella. Of 182 healthcare students, 179 (98.4%) were immune to measles, 163 (89.6%) were immune to mumps, and 176 (96.7%) were immune to rubella. Of 179 healthcare students, 151 (84.4%) were immune to hepatitis B virus. Of 178 healthcare students, 26 (14.6%) were immune to hepatitis A virus. Antibodies (10 IU/L or higher) to hepatitis B surface antigen were detected for 151 (84.4%) of 179 healthcare students, and antibodies (10 IU/L or higher) to hepatitis A virus were detected for 26 (14.6%) of 178 healthcare students. Fewer than 30% of participants were in full compliance with recommended vaccinations. CONCLUSIONS: We have determined that there is a certain proportion of healthcare students who are susceptible to certain vaccine-preventable diseases. The development of an appropriate vaccination strategy is required to decrease the risk of transmission in a hospital setting.

Multiple organ dysfunction syndrome pathogenesis and care: a complex systems' theory perspective.

AIMS AND OBJECTIVES: To discuss multiple organ dysfunction syndrome (MODS) from a complex systems' theory perspective and to delineate a conceptual framework for the development and care of MODS. BACKGROUND: MODS is an intricate and devastating manifestation of critical illness characterized by widespread aberrant molecular, cellular and systemic responses. DESIGN AND METHODS: Narrative literature review (MEDLINE, CINAHL databases) and knowledge synthesis with the theoretical assertions of chaos and complex systems' theory. Cellular and systemic response paradoxes in MODS (including cellular hypoxia, cell death and signalling) are reviewed. RESULTS: The diseased person is depicted as a complex adaptive system. The relevancy of some of the principles of complex chaotic systems' theory to the proposed model is illustrated, including sensitive dependence on initial conditions, emergence, attractors, self-organization, self-organized criticality and emerging order. The transition from life-supporting to death-related organismic responses is illustrated as a critical event in MODS and care implications are drawn. CONCLUSIONS: Patient responses in MODS appear to conform to the principles of chaotic systems. Death is illustrated not as a consequence of homeostatic failure but as a 'deliberate' self-organized phenomenon entailing multiple dynamically evolving mechanisms. RELEVANCE TO CLINICAL PRACTICE: Some of the principles of chaotic complex systems may need to be taken into account to advance care in MODS. An alternative theoretical perspective may support nurses to conceptualize both MODS and their role in a way that will help them to cope better with this devastating syndrome and develop practice.

VEGF isoforms and receptors expression throughout acute acetaminophen-induced liver injury and regeneration.

Acetaminophen (APAP) is a widely-used analgesic and a known hepatotoxic agent. Vascular endothelial growth factor (VEGF) is a growth factor with multiple functional roles. VEGF plays an important role in angiogenesis and hepatic regeneration. The aim of this study was to determine the expression of VEGF isoforms and its receptors throughout liver regeneration after the administration of a toxic dose of APAP in rats. Ten groups of adult male rats received a dose of 3.5 g/kg b.w. of APAP per os. The rats were killed post administration at 0-288 h. Blood and liver tissue were extracted. Determination of serum transaminases and alkaline phosphatase activities was performed. Liver injury and regeneration were assessed with hematoxylin-eosin specimens, morphometric analysis, hepatic thymidine kinase assay and Ki-67 expression. Reverse transcription-polymerase chain reaction and immunohistochemical methods were used for assessment of VEGF isoforms and receptors differential expression. High activities of aspartate aminotransferase were observed at 24 and 36 h with another peak of activity at 192 h post administration. Alanine aminotransferase was highest at 36 h. Alkaline phosphatase was increased post 24 h being higher at 72,192 and 240 h. Centrilobular necrosis was observed at 48-72 h and thorough restoration of the liver microarchitecture was observed at 288 h. Liver regeneration lasted from 24-192 h according to the results from thymidine kinase activity and Ki-67 expression. VEGF and VEGF receptor-2 m-RNA levels presented with a three-peak pattern of expression at 12-24, 72-96 and 192-240 h post administration. Significant difference was noted between periportal and centrilobular immunohistochemical expression. VEGF proves to play a critical role during APAP-induced liver regeneration as it presents with three points of higher expression. The first two time points are associated with the initial inflammatory reaction to the noxious stimulus and the hepatocyte regenerative process where as the third one is indicative of the potential involvement of VEGF in processes of remodeling.

Genomic variations and susceptibility to sepsis.

The considerable variability in septic patients' outcomes, which exceeds our understanding of the pathophysiology of sepsis and defies our current prognostic tools, has prompted investigation in the genetic variations that may predispose individuals for increased susceptibility to sepsis and adverse outcomes. This article aims to critically review current evidence from genetic association studies regarding the role of genetic polymorphisms in sepsis. Findings regarding polymorphisms in intercellular messenger mediators (cytokines), membrane-bound inflammatory receptors, intracellular signaling cascades, heat shock proteins, coagulation/fibrinolysis pathways, apoptotic mechanisms, and neuroendocrine axes are presented and discussed. Study results are often discrepant, whereas many methodological limitations, in terms of both study design and genotyping methods, may render the results difficult to generalize. Nonetheless, a role for genomic variations in sepsis outcomes has emerged. A theoretical framework for incorporation of genetic variations into individualized care planning based on complexity theory is proposed, and future prospects of microarray technology and systems modelling are discussed briefly.

HLA alleles and type 1 diabetes mellitus in low disease incidence populations of Southern Europe: a comparison of Greeks and Albanians.

Type 1 diabetes mellitus (DM1) is caused by environmental factors acting on genetically susceptible individuals. HLA-DQA1 and -DQB1 are major genetic determinants of the disease. Greece and Albania represent the low DM1 incidence countries of South-Eastern Europe. The HLA-DQA1 and -DQB1 associations with DM1 were investigated in these two groups, as reference for comparisons to the high-risk populations of Northern Europe. One hundred and thirty Greeks and 64 Albanians with DM1 were studied; 1,842 Greeks and 186 Albanians were analysed as controls. The samples were typed for six HLA-DQB1 alleles, using time-resolved fluorometry to detect the hybridisation of lanthanide labelled oligonucleotides with PCR products. Individuals positive for DQB1*0201 were selectively typed for three DQA1 alleles. In both populations DQB1*0201 increased the risk for DM1 while DQB1*0301 was protective. DQB1*0302 was associated with lower risk than *0201, while *0602 and *0603 were protective in Greeks but not in Albanians. It was also shown that DQA1 has a modifying effect, altering the risk conferred by the susceptible DQB1*0201. The low incidence of DM1 in these two countries correlates with the high frequency of the protective allele DQB1*0301 and the low impact of the susceptible DQB1*0302.