Search

Z uwagi na złożoną etiologię zaburzeń depresyjnych, uwzględniającą w ich powstawaniu i przebiegu interakcję czynników biologicznych i psychospołecznych, istotne jest kompleksowe oraz zintegrowane podejście do tego problemu zdrowotnego, uwzględniające poza tradycyjnymi metodami leczenia również dodatkowe formy oddziaływań, które mogą być pomocne w terapii. Jedną z nich jest zwiększenie aktywności fizycznej. Celem pracy jest przedstawienie znaczenia aktywności fizycznej w zapobieganiu i leczeniu zaburzeń depresyjnych w oparciu o wyniki badań przeprowadzonych w latach 2014 - 2019. Przeprowadzony przegląd badań wskazuje, iż dostosowana do potrzeb i stanu zdrowia aktywność fizyczna może pełnić rolę w zapobieganiu i uzupełniającą w terapii zaburzeń depresyjnych, w tym również tych, które występują w przebiegu schorzeń somatycznych. Rekomendując trening fizyczny w tej grupie osób, należy jednak mieć na uwadze, iż pochopne motywowanie pacjentów z ciężką postacią zaburzenia do tego typu aktywności, może uaktywniać ich poczucie winy z powodu trudności w sprostaniu wyzwaniu, prowokujące myśli i zachowania samobójcze.

Introduction. Alcoholism is a phenomenon with multi-factorial conditions and numerous health and socialconsequences, which makes its treatment a real challenge not only for the addict himself and his relatives, but alsofor the entire medical team involved in the therapy process. For this reason, in order to strengthen the therapeuticeffects of alcoholic disease, it is important to conduct research aimed at determining the factors that shape theeffectiveness of the implemented methods. With this in mind, it has been assumed that the aim of the research isto determine the relationship between the therapeutic methods used in the Clinical Alcohol Dependency TherapyUnit (COTUA), taking into account the tasks of a nurse, and the assessment of their effectiveness in the perceptionof patients after craniocerebral trauma with a diagnosis of alcohol disease.Material and Methods. 100 COTUA patients were tested, in which the diagnostic survey method was used and aquestionnaire was chosen as a technique.Results. The conducted analyses showed that, in the opinion of the respondents, the leading tasks of the nurses atCOTUA include informing patients about the principles and methods of therapy, familiarizing them with thetopography of the ward, the Charter of Patient’s Rights, the regulations of the ward, the schedule of the day and itsspecifics, administering medicines, providing a sense of safety, providing psychological support, transferring knowledgeand learning how to live with the disease and cooperating with the therapeutic team. In addition, three quarters ofthe respondents indicated that the nurses working in the ward are willing to talk to patients about alcohol dependence,and a comparable percentage of the respondents assessed the effectiveness of the therapeutic methods used by thetherapeutic team in relation to their own alcohol dependence problem very well and well.Conclusions. Patients’ assessment of the effectiveness of the therapeutic methods used depends on the nurses’ tasksof conducting therapeutic conversations with patients, providing them with knowledge, learning how to live withthe disease, cooperating with the therapeutic team and the nurses’ readiness to talk to patients about alcoholdependence. (JNNN 2021;10(1):26–34)

Description, A rapid test measures neutralizing antibodies against SARS-CoV-2 variants of concern in 1 hour., Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are concerning in the ongoing coronavirus disease 2019 (COVID-19) pandemic. Here, we developed a rapid test, termed CoVariant-SCAN, that detects neutralizing antibodies (nAbs) capable of blocking interactions between the angiotensin-converting enzyme 2 receptor and the spike protein of wild-type (WT) SARS-CoV-2 and three other variants: B.1.1.7, B.1.351, and P.1. Using CoVariant-SCAN, we assessed neutralization/blocking of monoclonal antibodies and plasma from COVID-19–positive and vaccinated individuals. For several monoclonal antibodies and most plasma samples, neutralization against B.1.351 and P.1 variants is diminished relative to WT, while B.1.1.7 is largely cross-neutralized. We also showed that we can rapidly adapt the platform to detect nAbs against an additional variant—B.1.617.2 (Delta)—without reengineering or reoptimizing the assay. Results using CoVariant-SCAN are consistent with live virus neutralization assays and demonstrate that this easy-to-deploy test could be used to rapidly assess nAb response against multiple SARS-CoV-2 variants.

The rise in rates of opioid abuse in recent years has led to an increase in the incidence of neonatal abstinence syndrome (NAS). Despite having a greater understanding of NAS and its symptoms, there still remains a lack of information surrounding the long-term effects of prenatal exposure to drugs of abuse on neurological development. One potential outcome of prenatal drug exposure that has been increasingly explored is disruption in normal synaptogenesis within the central nervous system. Both opioids and gabapentin, an antiepileptic drug commonly co-abused by opioid abuse disorder patients, have been shown to interfere with the normal functioning of astrocytes, non-neuronal glial cells known to serve many functions, including regulation of synaptic development. The goal of this study was to investigate the effects of prenatal drug exposure on synaptogenesis within brain regions associated with the mesolimbic dopamine pathway, the primary reward pathway within the brain associated with drug abuse and addiction, in a pregnant mouse model. Immunohistochemistry (IHC) and confocal fluorescence microscopy imaging studies on the brains of postnatal day 21 (P21) mouse pups revealed a significant increase in the mean number of excitatory synapses within the anterior cingulate cortex (ACC), nucleus accumbens (NAc), and prefrontal cortex (PFC) in mice that were prenatally exposed to either the opioid drug buprenorphine or gabapentin. These studies also revealed a significant decrease in the mean number of inhibitory synapses within the NAc and PFC of mice treated with buprenorphine. This observed net increase in excitatory signaling capability within the developing mesolimbic dopamine pathway suggests that exposure to drugs of abuse in utero can trigger maladaptive neuronal connectivity that persists beyond the earliest stages of life.

Introduction Depressive disorders are one of the most common psychiatric disorders. Recognition of signs of mental health disorders is not always easy, hence the availability of simple and accurate tools for assessing them is very important in the practice of primary care. Objective The aim of the study is to assess the theoretical accuracy and reliability of the Patient Health Questionnaire-9 (PHQ-9) in Polish conditions, when applied to general population studies for adults aged between 35–64. Material and methods The study comprised a population of 4,040 people. Women constituted 59% of the research population and people living in the countryside 65%. The average age of participants was 53.45 ± 7.05 years. According to PHQ-9, 727 people (18.0%) had moderate, moderate to severe or severe depression. PHQ-9 showed a significant positive internal cohesion (Cronbach’s alpha = 0.77), and factor charges oscillated between 0.43–0.63, and the R 2 coefficients of determination were in the range of 0.21–0.40. Conclusions The Polish version of PHQ-9 is a valid tool for diagnosing depression in the general population aged 35–64. Good psychometric properties and compactness make the PHQ-9 a useful clinical and research tool.

Introduction . Satisfaction of patients with nursing care is an important, subjective indicator of the quality of relational care, conditioned by the level of care provided and individual patient perception of care. The project adopted a compensation model for the satisfaction of patients with care. Aim . The aim of the work is to present what dimension of satisfaction from nursing is dominant among patients with lumbar spine pain syndrome and to determine whether their assessment depends on the severity of functional consequences of pain. Material and Methods . The research was performed using the diagnostic survey method and the survey technique. The research tools allowing for the collection of information were: Newcastle Satisfaction with Nursing Scale — NSNS and Visual Analog Scale by Barbara Headley. In addition, an original questionnaire was developed by the authors, taking into account medical and socio-demographic variables. The research was carried out from January to October 2017 among 205 patients of two neurosurgical clinics. The selection of patients for the research was purposeful. The project received a positive opinion of the Bioethics Committee at the Medical University in Lublin. Statistical analysis was performed using, among others, multivariate analysis of MANOVA variance in a mixed scheme. Results . In the assessment of patients with lumbar spine pain syndrome, the dominant dimension of satisfaction with nursing is the positive experience from the nursing care received at the ward (M = 5.66, SD = 0.56), and satisfaction with the care received is at a statistically significantly lower level (M = 3.05, SD = 0.48). The overall satisfaction with nursing is highest in patients displaying low (M = 4.40, SD = 0.49) and high (M = 4.43, SD = 0.53) functional consequences of pain. Conclusions . The results of the research compiled in the context of the compensatory satisfaction model indicate that patients formulating an opinion in terms of satisfaction with nursing are based on an objective assessment, i.e.: experienced care events. (JNNN 2019;8(1):4–10)

Introduction. As a result of involution processes and diseases, changes occur in the human body, as a result of which, psychophysical fitness declines with age. Comprehensive rehabilitation is the way of improving and maintaining health condition, including, among others, the appropriate level of physical activity and the quality of affective functioning. This type of program was carried out as part of the Outpatient Healthcare Home (DDOM) at the Witold Chodźko Institute of Rural Health in Lublin. Aim. The objective of the present study was to assess the impact of comprehensive ambulatory rehabilitation, including tailored endurance training preceded by an ergospirometry test, on indicators demonstrating the level of involvement in daily physical activities and the severity of depressive symptoms of patients over 60 years of age receiving health services at DDOM. Material and methods. The study involved 60 seniors participating in the rehabilitation cycle implemented as part of the services provided to patients at DDOM of the Witold Chodźko Institute of Rural Health in Lublin. The tests were carried out in the test-retest model on the first and last day of the kinesiotherapy cycle. The tests were performed with use of International Physical Activity Questionnaire IPAQ and Geriatric Depression Scale GDS. The patient rehabilitation program included adapted systemic kinesiotherapy (endurance training with a load determined according to individual exercise capacity, as determined on the basis of the ergospirometry test) and local kinesiotherapy and physical therapy adapted to the needs resulting from the condition of the musculoskeletal system. Results. After the completion of the rehabilitation cycle we compared the tests carried out before it, and the patients received higher scores in the scales of IPAQ questionnaire for measuring weekly, intensive and mode-rate physical activity and time required for walking and were less likely to spend their time sitting or lying down. There were also lower scores of the respondents in GDS scale used to assess the severity of depressive symptoms. Conclusions. As a result of the rehabilitation program applied, DDOM patients simultaneously obtained the desired changes in the level of involvement in physical activity and minimization of the intensity of depressive symptoms.

Introduction The answer to current social and health needs of people aged over 60 are the multidirectional and carefully planned, comprehensive activation and rehabilitation activities carried out as part of Daycare Centres (DCC). The aim of creating and the functioning of DCCs deployed all over Poland is to improve the health and psychophysical fitness of this group of people. Health factors and psychophysical fitness determine the ability to live independently, both today, and later in life. Objective The objective of the study was to assess the impact of comprehensive ambulatory rehabilitation, including tailored endurance training preceded by an ergospirometry test, on indicators demonstrating the ability to live independently and the risk ratio of future health problems in the elderly. Material and methods 60 people participating in a rehabilitation cycle implemented as part of the services provided to patients aged over 60 in the DCC of the Witold Chodźko Institute of Rural Medicine (IMW) in Lublin comprised the sample. The tests were carried out in the test-retest model on the first and last day of the kinesiotherapy cycle. Patients were tested using standardized Barthel, I-ADL and VES-13 questionnaires. The rehabilitation programme applied included systemic kinesiotherapy (endurance training) with a load determined according to individual exercise capacity, determined on the basis of a ergospirometry test, and varied rehabilitation activities resulting from the condition of the locomotor system, as provided for under the project. Results After completing the rehabilitation cycle, patients obtained higher results in comparison to the tests carried out before the beginning of the cycle in the Barthel index used to measure functional efficiency (Z = 5.41; p = 0.001), as well as lower in the I-ADL scale used to test the degree of dependence on the help of others when performing complex activities of everyday life (Z = 2.63; p = 0.009) and in VES-13 scale used to assess the risk of geriatric health problems (Z = 5.47; p = 0.001). Conclusions As the result of the use of comprehensive rehabilitation, including obligatory endurance training, desired changes were achieved in terms of fitness and independence in performing advanced daily activities and reducing the risk of geriatric health problems.

Introduction. The provision of adequate health care for a successively growing group of geriatric patients requires taking into account many factors in order to preserve and/or improve their overall health and the related functional capacity. Its crucial aspects include the ability to safely change position and locomotion, as well as the severity of discomfort from the osteoarticular system. Aim. The objective of the present study was to assess the impact of comprehensive ambulatory rehabilitation including tailored endurance training, preceded by an ergospirometry test, on indicators showing the risk of falls and the severity of pain symptoms of patients aged 60 and over, receiving health services at the Outpatient Healthcare Home (DDOM). Material and methods. The study involved 60 seniors during their rehabilitation cycle implemented as part of the services provided to patients at DDOM of the W. Chodźko Institute of Rural Health in Lublin. The tests were carried out in the test-retest model on the first and last day of the kinesiotherapy cycle. The Tinetti scale of the risk of falls, balance and walk and Visual Analogue Scale of the severity of pain sensations (VAS) were utilized in the research. The patient rehabilitation program at the DDOM included adapted systemic kinesiotherapy (endurance training with a load determined according to individual exercise capacity, as determined on the basis of the ergospirometry test) and local kinesiotherapy as well as physical therapy adapted to the needs resulting from the condition of the musculoskeletal system. Results. After completing the rehabilitation cycle, the patients obtained higher scores, compared to the tests carried out before the beginning of the rehabilitation cycle, in the scales of Tinetti Questionnaire. There were also lower results of the respondents in VAS scale used to assess the severity of pain sensations. Conclusions. As a result of the rehabilitation program applied, DDOM patients simultaneously obtained the desired changes in minimizing the risk of falls, improving the ability to maintain balance and fitness while walking, as well as reducing the severity of pain sensation.

Aim of study. The Fluoxetine Or Control Under Supervision (FOCUS)-Poland trial tested in a Polish cohort the hypothesis that fluoxetine improves recovery after stroke. Clinical rationale for study. Some studies have suggested that fluoxetine may improve functional outcomes after stroke, but these results needed confirmation. Between 2012 and 2014, large clinical trials were initiated by the FOCUS Trial Collaboration. Recently, results from the UK, Sweden, Australia, New Zealand and Vietnam have been published. We here present the results of the FOCUS trial conducted in Poland. Material and methods. This was a randomised, double-blind, placebo-controlled study based on the FOCUS trial protocol. Patients who had a persisting neurological deficit were randomly assigned 2-15 days after stroke onset to receive for six months either fluoxetine 20 mg/day or a placebo. The primary outcome was functional status measured using the modified Rankin Scale (mRS) at six months after randomisation. Functional status at 12 months was also assessed, as was neurological deficit at six and 12 months. Data was also collected on adverse events. Results. Between 19 December 2014 and 13 March 2018, 30 patients were given fluoxetine and 31 were given a placebo. For the primary outcome, the distribution across mRS categories was similar for the fluoxetine and placebo groups at six months (common odds ratio 0.88; 95% confidence interval 0.31–2.50; p = 0.81), and there was no difference at 12 months (p = 0.864). There were no differences between groups in stroke recovery or in motor function recovery of the affected hand. There were no significant differences in any other secondary outcomes at six or 12 months. Patients given fluoxetine were less likely than those given the placebo to receive new antidepressant medication within six months (2 [6.67%] vs. 4 [12.90%]). Conclusions and clinical implications. Consistent with other trials based on the FOCUS protocol, fluoxetine did not improve motor recovery or general stroke outcome at six and 12 months in the Polish cohort studied. However, patients receiving fluoxetine required therapy with additional antidepressant medication less frequently.

Background Several disease states commonly associated with methamphetamine (METH) use produce liver dysfunction, and in the bile duct ligation (BDL) model of hepatic dysfunction, rats with liver injury are more sensitive to METH effects. Additionally, both female rats and humans are known to be more sensitive to METH than males. In consideration of known sex-dependent differences in METH pharmacokinetics, this study sought to determine the potential interaction between sex and liver dysfunction variables on METH pharmacokinetics. Methods Sham or BDL surgery was performed on male and female rats on day 0. Serum biomarker and pharmacokinetics studies with 3 mg/kg subcutaneous (SC) METH were performed on day 7. METH-induced weight loss was measured on day 8. Liver histology evaluation and brain METH concentration measurements were performed on day 9. Results While BDL surgery produced significantly elevated alanine aminotransferase and bile duct proliferation in male compared to female rats, there were no significant interactions between sex and liver function in the pharmacokinetic parameters. Both liver dysfunction and female sex, however, were associated with significantly slower METH serum clearance and significantly higher brain METH concentrations (p Conclusions BDL-induced hepatic dysfunction produces substantial reductions in METH clearance and increased brain METH concentrations in both male and female rats, despite less liver injury in females. This preclinical model may be useful to identify and correct potential liver dysfunction comorbidity-related problems with future pharmacotherapy for stimulant use disorder with METH prior to expensive clinical trials.

The regulation of synaptic connectivity in the brain is vital to proper functioning and development of the central nervous system (CNS). Formation of neural networks in the CNS has been shown to be heavily influenced by astrocytes, which secrete factors, including thrombospondin (TSP) family proteins, that promote synaptogenesis. However, whether this process is different between males and females has not been thoroughly investigated. In this study, we found that cortical neurons purified from newborn male rats showed a significantly more robust synaptogenic response compared to female-derived cells when exposed to factors secreted from astrocytes. This difference was driven largely by the neuronal response to thrombospondin-2 (TSP2), which increased synapses in male neurons while showing no effect on female neurons. Blockade of endogenous 17β-estradiol production with letrozole normalized the TSP response between male and female cells, indicating a level of regulation by estrogen signaling. Our results suggest that male and female neurons show a divergent response to TSP synaptogenic signaling, contributing to sex differences in astrocyte-mediated synaptic connectivity. Significance Statement The regulation of synaptic connectivity by astrocytes has been a focus of both the neurodevelopmental and glial biology fields for nearly two decades, but many key findings did not take into account the possibility of sex differences. For the first time, we show that a prominent astrocyte signaling factor, thrombospondin-2, strongly promotes synapse formation in male but not female neurons. Furthermore, this sex difference can be abolished by inhibiting production of 17β-estradiol, revealing that this astrocyte synaptogenic pathway is regulated by estrogen. Our findings should prompt serious consideration into the ramifications of sex and sex hormones on astrocyte synaptic signaling as well as encourage and inform future studies, including potential implications for neurodevelopmental disorders that present with strong sex biases.

Summary Background Early and accurate identification of individuals with viral infections is crucial for clinical management and public health interventions. We aimed to assess the ability of transcriptomic biomarkers to identify naturally acquired respiratory viral infection before typical symptoms are present. Methods In this index-cluster study, we prospectively recruited a cohort of undergraduate students (aged 18–25 years) at Duke University (Durham, NC, USA) over a period of 5 academic years. To identify index cases, we monitored students for the entire academic year, for the presence and severity of eight symptoms of respiratory tract infection using a daily web-based survey, with symptoms rated on a scale of 0–4. Index cases were defined as individuals who reported a 6-point increase in cumulative daily symptom score. Suspected index cases were visited by study staff to confirm the presence of reported symptoms of illness and to collect biospecimen samples. We then identified clusters of close contacts of index cases (ie, individuals who lived in close proximity to index cases, close friends, and partners) who were presumed to be at increased risk of developing symptomatic respiratory tract infection while under observation. We monitored each close contact for 5 days for symptoms and viral shedding and measured transcriptomic responses at each timepoint each day using a blood-based 36-gene RT-PCR assay. Findings Between Sept 1, 2009, and April 10, 2015, we enrolled 1465 participants. Of 264 index cases with respiratory tract infection symptoms, 150 (57%) had a viral cause confirmed by RT-PCR. Of their 555 close contacts, 106 (19%) developed symptomatic respiratory tract infection with a proven viral cause during the observation window, of whom 60 (57%) had the same virus as their associated index case. Nine viruses were detected in total. The transcriptomic assay accurately predicted viral infection at the time of maximum symptom severity (mean area under the receiver operating characteristic curve [AUROC] 0·94 [95% CI 0·92–0·96]), as well as at 1 day (0·87 [95% CI 0·84–0·90]), 2 days (0·85 [0·82–0·88]), and 3 days (0·74 [0·71–0·77]) before peak illness, when symptoms were minimal or absent and 22 (62%) of 35 individuals, 25 (69%) of 36 individuals, and 24 (82%) of 29 individuals, respectively, had no detectable viral shedding. Interpretation Transcriptional biomarkers accurately predict and diagnose infection across diverse viral causes and stages of disease and thus might prove useful for guiding the administration of early effective therapy, quarantine decisions, and other clinical and public health interventions in the setting of endemic and pandemic infectious diseases. Funding US Defense Advanced Research Projects Agency.

Introduction and objective An important role in the pathogenesis of asthma in children is played by individual parameters and environmental factors, in particular, those related to the place of residence. The aim of this study was to assess the impact of the living environment on the basic demographic and clinical parameters of preschool children with IgE-dependent asthma. Material and methods 176 children (126 from urban and 52 from rural areas) aged 5.22±0.34 years, with newly-diagnosed IgE-dependent asthma, hospitalised at the Clinic for Lung Diseases and Paediatric Rheumatology of the Prof. Antoni Gębala Children’s Hospital of Lublin, were qualified for the study. Medical documentation of the children was analysed, including the implementation of vaccinations. Due to the clinical form of the disease, patients were separated into groups with mild, moderate and severe asthma. Results No statistically significant differentiation was observed between age and current body weight and height of the children. Similarly, gender and the clinical form of asthma were not significantly correlated with the place of residence. Children with asthma, at the time of exacerbation symptoms of the disease, living in a city, significantly more often (p

Introduction and objective Patient satisfaction with nursing care is one of important indicators of health care quality. As for pain, it is an indicator of patient health. The goal of the study is to identify socio-demographic and medical factors that differentiate the assessment of satisfaction with nursing care of hospitalized patients. Material and methods The study involved performing a diagnostic survey using standardized instruments, i.e. the Newcastle Satisfaction with Nursing Scale (NSNS) and the Visual Analog Scale by Barbara J. Headley for pain scoring. The study included 205 patients hospitalized for lumbar pain syndrome on two neurosurgery wards in Poland. The mean patient age was 51 years. Most respondents declared having high school or vocational education. The mean time of hospitalization before the study was 2 days. Results The results demonstrated that patient satisfaction with nursing care is independent of patient age, education, duration of hospitalization, or number of hospitalizations. In contrast, the experience of nursing care is dependent on education, and less educated patients (primary or vocational education) had higher scores in this category. With regards to pain, it was perceived as more intense by women and by patients hospitalized for a shorter period of time. Conclusions Satisfaction with nursing care among patients with lumbar pain syndrome does not depend on socio-demographic or medical variables. Experience of nursing care depends on patient's education.

RationaleAsthma exacerbations often occur due to infectious triggers, but determining whether infection is present and whether it is bacterial or viral remains clinically challenging. A diagnostic strategy that clarifies these uncertainties could enable personalized asthma treatment and mitigate antibiotic overuse.ObjectivesTo explore the performance of validated peripheral blood gene expression signatures in discriminating bacterial, viral, and noninfectious triggers in subjects with asthma exacerbations.MethodsSubjects with suspected asthma exacerbations of various etiologies were retrospectively selected for peripheral blood gene expression analysis from a pool of subjects previously enrolled in emergency departments with acute respiratory illness. RT-PCR quantified 87 gene targets, selected from microarray-based studies, followed by logistic regression modeling to define bacterial, viral, or noninfectious class. The model-predicted class was compared to clinical adjudication and procalcitonin.ResultsOf 46 subjects enrolled, 7 were clinically adjudicated as bacterial, 18 as viral, and 21 as noninfectious. Model prediction was congruent with clinical adjudication in 15/18 viral and 13/21 noninfectious cases, but only 1/7 bacterial cases. None of the adjudicated bacterial cases had confirmatory microbiology; the precise etiology in this group was uncertain. Procalcitonin classified only one subject in the cohort as bacterial. 47.8% of subjects received antibiotics.ConclusionsOur model classified asthma exacerbations by the underlying bacterial, viral, and noninfectious host response. Compared to clinical adjudication, the majority of discordances occurred in the bacterial group, due to either imperfect adjudication or model misclassification. Bacterial infection was identified infrequently by all classification schemes, but nearly half of subjects were prescribed antibiotics. A gene expression-based approach may offer useful diagnostic information in this population and guide appropriate antibiotic use.

Aim. The aim of the study was to determine the relation between existential attitudes and occupational burnout in nurses. Material and methods. The research sample consisted of 120 nurses. Life Attitudes Profile - Revised (the LAP-R) adapted by R. Klamut and Link Burnout Questionnaire (the LBQ) adapted by A. Jaworowska were used in the research. Results. Psycho-physical exhaustion and relationship deterioration correlate negatively with life goals, internal consistency, life control, death acceptance and positively with existential void and goal seeking. Sense of professional failure and disillusion present a conversely proportional relation with goal, coherence, life control as well as an inversely proportional relation with existential void and goal seeking. Conclusions. The analyses performed in the course of the research proved that existential attitudes accompany burnout in nurses. The obtained results of the authors’ own research present cognitive value and can be used to develop both prevention and aid programs aimed at enhancing the quality of personal and professional functioning of nurses.

Introduction One possible way of iron loss is sweating. It is unclear how physical activity performed by untrained individuals affects the iron status in sweat. Objective The purpose of this study was to analyse iron concentration in sweat during 4-week exercise training to determine the changes in iron excretion during follow-up exercises. Material and methods 43 untrained volunteers participated in the study, 29 of whom completed the full exercise programme. The training programme consisted of exercises on a cycle ergometer and cross-trainer. In the first week, participants exercised for 8 minutes on each device, in the second for 10 minutes, and in the third and fourth weeks they exercised for 15 min on each device. Intensity was submaximal and defined as 85% of maximal heart rate. A sterile sweat patch was placed on the skin between shoulder blades. Results Concentration of iron on the first and the fifteenth day of exercises was comparable and statistically insignificant. Iron concentration was highly increased on the last day of training in comparison with first (p

BACKGROUND: Pneumonia is a common complication of hospitalisation in severely ill patients who need mechanical ventilation. The aim of this study was to assess the usefulness of the International Nosocomial Infection Control Consortium programme for the surveillance of ventilator-associated pneumonia (VAP). METHODS: A prospective study (1 Jan 2012−30 June 2014) was conducted in the 20-bed ICU. The device utilisation ratios for lung ventilation and the frequency (density and incidence) and aetiology of VAP were estimated in ICU patients. RESULTS: From a total of 1097 patients, VAP infections were diagnosed in 93. Thirty percent of patients with VAP died. The incidence index was 8.47 per 100 admissions to the ICU. VAP infections accounted for 46% of the overall count of device-associated healthcare-associated infections. Mechanical ventilation was used in 71 ± 8 patients during the 11 862 patient days and 8425 ventilation days. The rate of VAP per 1000 ventilator days was 11.15/9.34 /10.23 in years 2012/2013/2014 (half a year), respectively. The main VAP pathogens were Acinetobacter baumannii (45%) and Pseudomonas aeruginosa (17%). CONCLUSION: During the reported time span, the incidence of VAP was lower than in the INICC report (2007–2012), but it was tenfold higher than in the NHSN/CDC report (dated 2012). Because of the unchanged VAP level during the 2.5-year observation period, the root cause needs to be determined and action should be taken to resolve this issue.

Background Bacterial and viral infections are difficult to clinically distinguish, leading to antibiotic overuse and resistance. Host response signatures are an alternative to traditional pathogen-detection methods to differentiate these etiologies. Several gene expression signatures have been described although performance in ambiguous clinical phenotypes is unknown. Here, we validate a host response signature and explore its performance in microbiology-negative and co-infection cases. Methods RT-PCR taqman low-density array (TLDA) was used to measure 87 gene targets in a training cohort of 151 samples from patients with microbiologically confirmed and clinically adjudicated phenotypes (48 bacterial; 54 viral; 49 non-infectious illness [NI]). This data were used to construct three distinct classifiers: bacterial vs. nonbacterial; viral vs. nonviral; and non-infectious vs. infectious. This model was then applied to 75 subjects with co-infection and 40 suspected bacterial cases without microbiological confirmation. Results Leave-one-out cross validation on the training cohort demonstrated AUC values of 0.85, 0.89, and 0.88 for bacterial, viral, and NI, respectively. In 40 subjects with microbiology-negative bacterial infections, a bacterial or co-infection signature was present in 72%. Of 75 subjects with co-infection, 53 included a bacterial infection following recent viral infection and 22 were bacterial infections in patients with chronic viral infection (e.g., HCV, HIV). Bacterial infection and co-infection were successfully identified in these varied scenarios. Conclusion This gene expression signature distinguished bacterial, viral, and noninfectious causes of illness. The host response was able to confirm the majority of suspected bacterial infection without confirmatory microbiology but also highlighted a viral response in many. Furthermore, the use of distinct viral and bacterial signatures was capable of identifying co-infection. Such a host gene expression strategy, when translated to a clinically useful platform, can offer new insights into the etiology of both simple and complex cases that are not currently available. Disclosures G. S. Ginsburg, Host Response Inc.: Board Member, Founder, Scientific Advisor and Shareholder, Stock (currently worth

Background Despite advances in molecular techniques the etiology of acute respiratory infections (ARIs) is often difficult to differentiate either at the point of care or with advanced microbiological techniques. There is growing interest in host biomarker assays, including those based on gene expression patterns in circulating cells, to aid in differentiation of viral and bacterial diseases. However, there are concerns about how such tests perform in vulnerable aging populations where host responses are often muted. Methods In order to assess performance of gene expression-based biomarkers, we enrolled patients presenting to the emergency department with clinical ARI and selected 184 individuals aged ≤25 and ≥60 years old with proven viral or bacterial ARI. Gene expression in peripheral blood was measured with Affymetrix microarrays. Published viral and bacterial signatures were applied to the data and Bayesian approaches were used to develop novel discriminative models. Results We noted a marked decline in signature performance between younger and older individuals in both viral (AUC 0.90 vs. 0.64) and bacterial (AUC 0.91 vs. 0.50) infections. Incorporation of age-related genomic changes was able to restore much of the signature performance in older individuals. When examining the genomic differences driving the drop in signature performance, we found marked perturbations in expression of immunoglobulin genes and pathways driving known immunoregulatory mechanisms that provide novel insights into an age-related decline in ARI-focused immunity. Conclusion Pathogen class-specific host-based gene expression signatures offer great promise as diagnostic tools. However, altered immune responses in vulnerable populations such as the elderly are also manifested at the genomic level and can affect diagnostic signature performance. Age-specific alterations in the components of a diagnostic signature can minimize much of this effect, however this work highlights the need for consideration of age during biomarker development for infectious diseases. Furthermore, studies of age-related differences in biomarker performance can lead to important breakthroughs in our understanding of age-associated alterations in immunity. Disclosures All authors: No reported disclosures.

Background Asthma exacerbations often occur due to infectious triggers. However, determining whether an infection is present and whether it is bacterial or viral remains clinically challenging leading to antibiotic overuse. A diagnostic strategy that clarifies these uncertainties can enable personalized asthma treatment and mitigate antibiotic resistance. Host gene expression is a promising alternative to pathogen-detection methods. Methods Forty-six patients presenting to the emergency department with asthma exacerbations were enrolled. Cases were clinically adjudicated as having bacterial, viral, or non-infectious etiologies. RT-PCR taqman low density array (TLDA) was used to quantify 87 gene targets, followed by logistic regression modeling to define class. Etiologies were correlated with clinical information including symptoms and antibiotic prescriptions. Results Most clinical parameters were similar between groups including duration of symptoms, presence of sick contacts, and severity of nasal symptoms, cough, headache, throat discomfort, and malaise. Only fever/chills (P = 0.006) and a composite of all symptoms (P = 0.02) were significantly different. In contrast to clinically adjudicated phenotypes, host response signatures identified very few bacterial triggers. Notably, none of the adjudicated bacterial cases had positive confirmatory microbiology. Instead, 29 and 57% were identified as having a viral infection or no infection, respectively. Despite the absence of bacterial infections identified using host gene expression, antibiotics were prescribed in 47.8% of all cases. Conclusion Host response signatures indicated that asthma exacerbation is infrequently caused by bacterial infections, even when clinical adjudications suggest this to be the case. Instead, most are either of viral or non-infectious etiologies. Despite most cases being classified as nonbacterial, empiric antibiotics were prescribed nearly half the time. A host gene expression approach can offer clinically useful diagnostic information to guide more appropriate antibiotic use among patients with asthma exacerbation. Disclosures G. S. Ginsburg, Host Response Inc.: Board Member, Founder, Scientific Advisor and Shareholder, Stock (currently worth < $100). C. W. Woods, Host Response: Founder, Licensing agreement or royalty; Qvella: Collaborator, Research support; BioFire: Collaborator, none. E. L. Tsalik, Host Response, Inc.: Founder, Equity.

Acute respiratory infections caused by bacterial or viral pathogens are among the most common reasons for seeking medical care. Despite improvements in pathogen-based diagnostics, most patients receive inappropriate antibiotics. Host response biomarkers offer an alternative diagnostic approach to direct antimicrobial use. This observational, cohort study determined whether host gene expression patterns discriminate non-infectious from infectious illness, and bacterial from viral causes of acute respiratory infection in the acute care setting. Peripheral whole blood gene expression from 273 subjects with community-onset acute respiratory infection (ARI) or non-infectious illness as well as 44 healthy controls was measured using microarrays. Sparse logistic regression was used to develop classifiers for bacterial ARI (71 probes), viral ARI (33 probes), or a non-infectious cause of illness (26 probes). Overall accuracy was 87% (238/273 concordant with clinical adjudication), which was more accurate than procalcitonin (78%, p

The use of psychoactive medications to augment behavioral and psychosocial interventions in schools has significantly increased within the last few decades. Yet, advising, administrating, and supervising the dispensation of medication (including psychostimulants and psychoactive substances) tend to be some of the most risky tasks of school administrators and personnel. Medication administration is not only an increasing source of civil and administrative liability for school districts, but may lead to legal questions for school counselors, psychologists, and social workers. In response to growing concerns, this article provides guidelines necessary for safe medication administration and monitoring in the school setting. Federal, state, and district guidelines are reviewed. Possible implications for school and district policy makers, principals, teachers, school nurses, school psychologists, social workers, counselors, and parents are outlined. © 2009 Wiley Periodicals, Inc.

Tetrahydrocannabinol (Delta(9)-THC), the primary psychoactive ingredient in marijuana, is subject to cytochrome P450 oxidation and subsequent UDP-glucuronosyltransferase (UGT)-dependent glucuronidation. Many studies have shown that CYP2C9 and CYP3A4 are the primary enzymes responsible for these cytochrome P450-dependent oxidations, but little work has been done to characterize phase II metabolic pathways. In this study, we test the hypothesis that there are specific human UGTs responsible for classic cannabinoid metabolism. The activities of 12 human recombinant UGTs toward classic cannabinoids [cannabinol (CBN), cannabidiol (CBD), (-)-Delta(8)-THC, (-)-Delta(9)-THC, (+/-)-11-hydroxy-Delta(9)-THC (THC-OH), and (-)-11-nor-9-carboxy-Delta(9)-THC (THC-COOH)] were evaluated using high-performance liquid chromatography-tandem mass spectrometry and labeling assays. Despite activity by UGT1A1, 1A3, 1A8, 1A9, 1A10, and 2B7 toward CBN, CBD, THC-OH, and THC-COOH, only selected UGTs demonstrate sufficient activity for further characterization of steady-state kinetics. CBN was the most recognized substrate as evidenced by activities from hepatic UGT1A9 and extrahepatic UGT1A7, UGT1A8, and UGT1A10. These results may reflect the introduction of an aromatic ring to Delta(9)-THC, leading to favorable pi stacking with phenylalanines in the UGT active site. Likewise, oxidation of Delta(9)-THC to THC-OH results in UGT1A9 and UGT1A10 activity toward the cannabinoid. Further oxidation to THC-COOH surprisingly leads to a loss in metabolism by UGT1A9 and UGT1A10, while creating a substrate recognized by UGT1A1 and UGT1A3. The resulting glucuronide of THC-COOH is the main metabolite found in urine, and thus these hepatic enzymes play a critical role in the metabolic clearance of cannabinoids. Taken together, glucuronidation of cannabinoids depends on upstream processing including enzymes such as CYP2C9 and CYP3A4.

Inflammation is associated with modifications of the extracellular matrix (ECM) that are recognized by receptors expressed by a variety of inflammatory cells. During inflammation, fibroblasts are a...

Fibroblast activation protein-α (FAP) is a serine protease that can provide target specificity to therapeutic agents because in adults its expression is restricted to pathologic sites, including cancer, fibrosis, arthritis, wounding, or inflammation. It is not expressed in most normal tissues. The majority of FAP is expressed by activated fibroblasts responding to the pathologic situations. FAP is typically found as a type II transmembrane protein physically attached to cells and with the bulk of the protein, including the catalytic domain, exposed to the extracellular space and accessible to small molecules. In this chapter, we review the structure, substrate specificities, signaling functions, and current design of FAP inhibitors. Evidence indicating the presence of FAP in multiple cancers, arthritis, fibrosis, keloids, and other pathologies is described and indicates possible roles for FAP in facilitating cell invasion and growth. Separate sections are devoted to the role of FAP in coordinating the stromal response to cancer, including a role in angiogenesis and a potential role in modulation of the antitumor immune response. Finally studies attempting to demonstrate the clinical potential of FAP are discussed, as well as some novel applications employing FAP in therapy or diagnosis. Throughout this review, effort is made to highlight areas where information is lacking and to highlight important questions that require further investigation.

Sensory and motor functions are good markers of neurocognitive decline due to their proximity and hierarchical relationship to high-order processes. The current study investigated if patients with Alzheimer's disease (AD) differed from a healthy control group in two tactile perceptual processes: astereognosis and agraphesthesia. Analyses were also conducted to see if these tactile processes were predictive of higher-order cognitive functioning. Twenty-eight patients with AD (mean age = 75.86) were compared to 28 healthy control subjects (mean age = 76.38) and were administered the Dean-Woodcock Sensory Motor Battery and the Woodcock-Johnson Psychoeducational Battery-Revised. Results suggest the patients with AD demonstrated significantly higher levels of tactile disturbance and astereognosis while agraphesthesia was able to predict a substantial portion of the variance in 3/7 cognitive tests and 4/7 cognitive tests, respectively. This included measures of fluid reasoning, visual processing, crystallized language, short-term memory, and auditory processing. These results suggest that astereognosis and agraphesthesia may be good markers of the extent of cognitive impairment in AD and should be included in neuropsychological evaluations due to their functional importance.

Fibroblast activation protein-α (FAP) is a cell surface, serine protease of the post-prolyl peptidase family that is expressed in human breast cancer but not in normal tissues. Previously, we showed that FAP expression increased tumor growth rates in a mouse model of human breast cancer. Here the role of the proteolytic activities of FAP in promoting tumor growth, matrix degradation and invasion was investigated. Mammary fat pads of female SCID mice were inoculated with breast cancer cells that express FAP and the mice treated with normal saline or Val-boroPro (talabostat); Glu-boroPro (PT-630); or 1-[[(3-hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine (LAF-237) that inhibit prolyl peptidases. Other mice were injected with breast cancer cells expressing a catalytically inactive mutant of FAP and did not receive inhibitor treatment. PT-630 and LAF-237 did not slow growth of tumors produced by any of the three cell lines expressing FAP. Talabostat slightly decreased the growth rates of the FAP-expressing tumors but because PT-630 and LAF-237 did not, the growth retardation was likely not related to the inhibition of FAP or the related post-prolyl peptidase dipeptidyl peptidase IV. Breast cancer cells expressing a catalytically inactive mutant of FAP (FAP(S624A)) also produced tumors that grew rapidly. In vitro studies revealed that cells expressing wild type FAP or FAP(S624A) degrade extracellular matrix (ECM) more extensively, accumulate higher levels of matrix metalloproteinase-9 (MMP-9) in conditioned medium, are more invasive in type I collagen gels, and have altered signaling compared to control transfectants that do not express FAP and form slow growing tumors. We conclude that the proteolytic activity of FAP participates in matrix degradation, but other functions of the protein stimulate increased tumor growth.

To the Editor: We read with much interest an excellent and thorough review published in the January issue of Kidney International by Siew and Davenport on an alarming increase in incidence of acute kidney injury (AKI) in North America and Western Europe.1 The question asked by the Authors, namely whether these changes reflect the real rise or are rather driven by better diagnostics, reimbursement issues, and a more liberal use of dialysis, seems to be crucial and should prompt future well-designed studies. Therefore, we would like to share our experience. Recently, we retrospectively analyzed the data obtained from individual hospital records of 774 consecutive patients with AKI, as defined by KDIGO criteria,2 requiring dialysis (AKI-D) in our single university hospital between Jan 2005 and Dec 2009. A subgroup of 126 patients, residents of three identifiable districts of Warsaw covered by the hospital with an estimated adult population of 149,687, were isolated to count the incidence.