First-in-human study of CPL207280, a novel G-protein-coupled receptor 40/free fatty acid receptor 1 agonist, in healthy volunteers after single and multiple administration.

AIM: To assess the safety, tolerability and pharmacokinetic (PK) profile of single and multiple doses of CPL207280, a new G-protein-coupled receptor 40 agonist developed to treat type 2 diabetes (T2D). METHODS: The phase 1 study in healthy volunteers (White, age 18-55 years, body mass index 18.5-29.9 kg/m2 ) was performed after single (24 subjects, 5-480 mg) and multiple (32 subjects, 60-480 mg) once-daily administration of CPL207280.  The effect of food intake and interaction with metformin were evaluated in additional cohort (12 subjects, 120 mg). The primary objective was the safety and tolerability of CPL207280. Secondary objectives included PK and pharmacodynamic (PD) characteristics (glucose, insulin, C-peptide, proinsulin, glucagon levels) observed during the 14-day treatment period. RESULTS: No deaths or serious adverse events (AEs) were reported. All reported AEs were classified as unrelated to the study product. No clinically significant differences in safety parameters were observed between cohorts and no food or metformin effect on safety parameters was identified. The ascending dose of CPL207280 caused an increase in the PK parameters maximum observed plasma concentration (Cmax ) or area under the plasma concentration-time curve up to 24 h. However, dose-normalized Cmax decreased with ascending dose. There was no relationship between the CPL207280 dose or prandial state and terminal elimination half-life and terminal elimination rate constant. No clear relationship between CPL207280 dose and PD area under the effect curve values was observed. CONCLUSIONS: CPL207280 was found to be safe and well tolerated by healthy volunteers (with a low risk of hepatotoxicity) for up to 14 days of administration. The PK profile of CPL207280 supports single-daily administration and justifies further development of this therapy for patients with T2D.

Data-driven case fatality rate estimation for the primary lineage of SARS-CoV-2 in Poland.

After more than one and a half year since the COVID-19 pandemics outbreak the scientific world is constantly trying to understand its dynamics. In this paper of the case fatality rates (CFR) for COVID-19 we study the historic data regarding mortality in Poland during the first six months of pandemic, when no SARS-CoV-2 variants of concern were present among infected. To this end, we apply competing risk models to perform both uni- and multivariate analyses on specific subpopulations selected by different factors including the key indicators: age, sex, hospitalization. The study explores the case fatality rate to find out its decreasing trend in time. Furthermore, we describe the differences in mortality among hospitalized and other cases indicating a sudden increase of mortality among hospitalized cases at the end of the 2020 spring season. Exploratory and multivariate analysis revealed the real impact of each variable and besides the expected factors indicating increased mortality (age, comorbidities) we track more non-obvious indicators. Recent medical care as well as the identification of the source contact, independently of the comorbidities, significantly impact an individual mortality risk. As a result, the study provides a twofold insight into the COVID-19 mortality in Poland. On one hand we explore mortality in different groups with respect to different variables, on the other we indicate novel factors that may be crucial in reducing mortality. The later can be coped, e.g. by more efficient contact tracing and proper organization and management of the health care system to accompany those who need medical care independently of comorbidities or COVID-19 infection.

Longitudinal Evaluation of Biomarkers in Wound Fluids from Venous Leg Ulcers and Split-thickness Skin Graft Donor Site Wounds Treated with a Protease-modulating Wound Dressing.

Venous leg ulcers represent a clinical challenge and impair the quality of life of patients. This study examines impaired wound healing in venous leg ulcers at the molecular level. Protein expression patterns for biomarkers were analysed in venous leg ulcer wound fluids from 57 patients treated with a protease-modulating polyacrylate wound dressing for 12 weeks, and compared with exudates from 10 acute split-thickness wounds. Wound healing improved in the venous leg ulcer wounds: 61.4% of the 57 patients with venous leg ulcer achieved a relative wound area reduction of ≥ 40%, and 50.9% of the total 57 patients achieved a relative wound area reduction of ≥ 60%. Within the first 14 days, abundances of S100A8, S100A9, neutrophil elastase, matrix metalloproteinase-2, and fibronectin in venous leg ulcer exudates decreased significantly and remained stable, yet higher than in acute wounds. Interleukin-1ß, tumour necrosis factor alpha, and matrix metalloproteinase-9 abundance ranges were similar in venous leg ulcers and acute wound fluids. Collagen (I) α1 abundance was higher in venous leg ulcer wound fluids and was not significantly regulated. Overall, significant biomarker changes occurred in the first 14 days before a clinically robust healing response in the venous leg ulcer cohort.

An observational study of wounds treated with hydro-responsive wound dressings.

OBJECTIVE: Acute and hard-to-heal wounds are a significant burden to both a patient's quality of life and resources in healthcare systems. Here, we evaluate the outcomes of a non-comparative case series study in which Ringer's solution-preactivated polyacrylate dressings were used to treat acute and hard-to-heal wounds (the presence of Ringer's solution provides a wound dressing that allows, upon application, the immediate hydration of the underlying wound tissue). METHOD: Patients with acute and hard-to-heal wounds were enrolled into an open-labelled, non-comparative observational study. Patients were treated with Ringer's solution-preactivated polyacrylate dressings to enable wound debridement and wound cleansing for up to 12 weeks. RESULTS: A total of 303 patients were enrolled in the study and 278 were included in the analysis. Wound size decreased, from a median of 3.6cm2 (interquartile range (IQR): 1.2-9.3] at baseline to a median of 2.6cm2 (IQR: 1.1-7.8] at 84 days. Relative wound area reduction (WAR) was 43.1% at 84 days and estimated probability of achievement of a WAR of ≥40% and ≥60% was 68.7% and 53.4%, respectively. Median time to achieve a WAR of ≥40% and ≥60% was 54 days and 75 days, respectively. The median percentage of wound area covered by fibrin had decreased from 50.0% to 10% and granulation tissue had increased from 25% to 50% after 84 days. In addition, periwound skin condition, local signs of infection and pain all showed improvement. The majority of the wounds were assessed as 'healed' or 'better' at the conclusion of the evaluation period. CONCLUSION: Based on the findings of this study, the use of Ringer's solution-preactivated polyacrylate dressings in daily practice has the potential to improve clinical outcomes, including healing, in patients with acute and hard-to-heal wounds.

Factors determining adherence to guidelines and restrictions during the initial period of the COVID-19 pandemic in Poland before the vaccination rollout.

INTRODUCTION: In Poland, like in many other countries, guidelines and certain restrictions were introduced in order to reduce the impact of the pandemic and curb the spread of the virus. These related to such behaviours as washing and disinfecting hands, wearing face masks in designated places, keeping social distance and frequently ventilating rooms. However, not all people follow the guidelines, which can lead to both health and social ramifications. The key objective of this study was an in-depth analysis of how safety rules (SR) were complied with in Poland during the initial pandemic period before the vaccines were rolled out, as well as determining factors that could affect the compliance with SR. METHODS: The study was conducted in the form of a series of cross-sectional surveys using the CATI method on a representative Polish sample in 8 rounds of interviews. Random sampling was applied. The first round was carried out from 2 to 6 July 2020, the last from 17 to 21 August 2020. The authors' original survey questionnaire was used. Factors affecting the compliance with SR were analysed using the multivariate logistic regression method on a combined group of participants from all the study rounds. RESULTS: In total, 4,800 subjects participated in the study, of which 2,512 were women (52.3%) and 2,288 were men (47.7%). Compliance with guidelines was defined based on four survey questions relating to: disinfecting hands when not at home, not touching items with bare hands when not at home, wearing face masks or covering mouth and nose, as well as washing hands after coming back home. Two affirmative answers to these questions or wearing a face mask alone (covering mouth and nose) were interpreted as compliance with SR. SR were more frequently followed by women OR=1.234 95% CI (0.988-1.543), persons over the age of 65 OR=2.098 95% CI (1.409-3.122), people with university education OR=1.315 95% CI (0.950-1.820) and residents of large cities OR=2.179 95% CI (1.382-3.437). Factors that supported compliance with SR were older age, fear of contracting COVID-19 and knowledge of SR. DISCUSSION AND CONCLUSIONS: During the first wave of the pandemic, the SR compliance level was high. Nevertheless, the study identified social groups with a higher risk of non-compliance. This indicates a need for properly addressing communication to these groups, especially that, as was demonstrated, the knowledge alone of pandemic-related messages significantly increased the likelihood of following SR and restrictions. The study of infection-preventing behaviours and their context may provide essential information to guide public policies and communication strategies that would support these behaviours in order to control the spread of the virus more effectively.

Features of personality and professional burnout syndrome of physicians - analysis based on questionnaires studies.

INTRODUCTION: This observational study was ordered by the Medical Practitioners' Chamber in Warsaw. THE OBJECTIVE: of the study was to evaluate the problem of professional burnout of physicians correlation between professional burnout and features of personality. MATERIAL AND METHODS: Professional burnout was considered relative to different features of personality. This study was initially carried out from 2005-2008, but further analysis of burnout and personality was carried out from 2017-2018. The research tools were anonymous, validated questionnaires. The sample size was based on the size of the population- the registry of the Regional Chamber of Medical Practitioners and literature on burnout prevalence. The respondents' work places were randomly selected from the Mazovian District register. RESULTS: The test on burnout was completed by 378 respondents, while 62 subjects completed a personality test. Results showed that burnout syndrome was an occupational problem for healthcare workers. Professional burnout affected as many as 42% of respondents (n = 158). It affected two age groups in particular: physicians up to 31 years old and individuals aged 41-50. Moreover, neuroticism was found to be significantly related to burnout syndrome. CONCLUSION: burnout syndrome is common among professionally active medical practitioners, and neuroticism may be correlated with burnout syndrome.

Adverse Reactions in Antifolate-Treated Toxoplasmic Retinochoroiditis.

This study seeks to define factors affecting the development of adverse reactions to intensive therapy of toxoplasmic retinochoroiditis with antifolate agents (pyrimethamine/sulfadoxine) and antibiotics followed by secondary antifolate prophylaxis. The study was of retrospective and observational nature. Medical files were reviewed of 551 patients suffering from ocular toxoplasmosis during 1994-2013. All patients were treated with the same protocol: 3-week intensive pyrimethamine/sulfadoxine plus antibiotic/steroid therapy. Three hundred and fourteen out of the 551 patients qualified for the subsequent 6-month long secondary antifolate prophylaxis. The type and occurrence rate of adverse reactions were taken into account. The probability of an adverse reaction during the intensive therapy phase was 33.4%. Hypertransaminasemia was the most common event observed in 24.6% of the patients, but it assumed a severe character in just 0.9%, with male gender and age over 25 years being the predisposing factors. Less common adverse effects included thrombocytopenia (8.3%), hypersensitivity skin reactions (3.0%), and abdominal pain (1.4%). The adverse effects of secondary antifolate prophylaxis, most commonly hypersensitivity skin reactions and hypertransaminasemia, followed by thrombocytopenia and abdominal pain, were observed in 4.9% of the patients. Ten of them (2.7%) had to discontinue the treatment while eight others continued with pyrimethamine alone without further adverse effects, which suggests that discontinuation of the sulfonamide decreased the propensity for adverse reactions. The treatment strategy in these patients differed from previous reports in that it used lower doses of pyrimethamine/sulfonamide, with no folinic acid supplementation. Nonetheless, the rate and severity of adverse events were no greater than those noticed with traditional regimens, with higher antifolate doses and folinic acid supplementation. We conclude that the dose and drug-mitigated treatment strategy we employed deserves consideration as a promising alternative to traditional treatments for ocular toxoplasmosis.

Seroprevalence of Bartonella Species in Patients with Ocular Inflammation.

Bartonella species, vector-borne etiologic agents of many systemic or self-limited infections, are responsible for a widening spectrum of diseases in humans, including inflammatory conditions of the eye. The aim of this study was to determine whether there is any relationship between uveitis and the evidence of Bartonella spp. infection in the serum, ocular fluid, and cataract mass in patients with intraocular inflammation. Polymerase chain reaction (PCR)-based tests and DNA sequencing were performed on surgery-extracted specimens of intraocular fluid and lens mass of 33 patients. Sera from 51 patients and 101 control subjects were tested for the presence of specific antibodies against Bartonella spp. Neither IgM-class antibodies against Bartonella spp. nor Bartonella spp. DNA were detected. A specific IgG-class antibody was found in 33.3% of the patients with uveitis. The rate of positive Bartonella serology was higher among the uveitis patients than that in control subjects. This high rate may in part result from unrecognized indirect mechanisms rather than the immediate presence and multiplication of Bartonella spp. in the eyeball. Nonetheless we believe that screening for Bartonella spp. should become part of the diagnostic workup in uveitis.

Characterization and Optimization of Biosynthesis of Bioactive Secondary Metabolites Produced by Streptomyces sp. 8812.

The nutritional requirements and environmental conditions for a submerged culture of Streptomyces sp. 8812 were determined. Batch and fed-batch Streptomyces sp. 8812 fermentations were conducted to obtain high activity of secondary metabolites. In the study several factors were examined for their influence on the biosynthesis of the active metabolites-7-hydroxy-6-oxo-2,3,4,6-tetrahydroisoquinoline-3-carboxy acid (C10H9NO4) and N-acetyl-3,4-dihydroxy-L-phenylalanine (C11H13NO5): changes in medium composition, pH of production medium, various growth phases of seed culture, amino acid supplementation and addition of anion exchange resin to the submerged culture. Biological activities of secondary metabolites were examined with the use of DD-carboxypeptidase 64-575 and horseradish peroxidase. Streptomyces sp. 8812 mycelium was evaluated under fluorescent microscopy and respiratory activity of the strain was analyzed. Moreover, the enzymatic profiles of the strain with the use of Api ZYM test were analyzed and genetic analysis made. Phylogenetic analysis of Streptomyces sp. 8812 revealed that its closest relative is Streptomyces capoamus JCM 4734 (98%), whereas sequence analysis for 16S rRNA gene using NCBI BLAST algorithm showed 100% homology between these two strains. Biosynthetic processes, mycelium growth and enzyme inhibitory activities of these two strains were also compared.

Association between high temperature and mortality of Warsaw inhabitants, 2008-2013 / Zwiazek umieralnosci mieszkanców Warszawy z wysoka temperatura powietrza, w latach 2008-2013

Different aspects of association between daily maximum temperature and daily number of deaths from all causes (excluding external) in Warsaw in periods of warm months (May - September) in years 2008-2013 were analysed. Analysis of dependence between temperature and mortality for whole population as well as for subpopulations with respect to sex and age demonstrated its similar U-shape. For each subpopulation a value of temperature at which dependence of mortality from temperature is changing its character from decreasing to increasing, interpreted as comfort conditions, was computed. Its value varied between 20 and 24oC with slight tendency to be higher for woman. Heat waves defined as at least three consecutive days with maximal temperature higher than 30oC have additional (to temperature effect itself ) effect on male mortality however, only in males aged 70 years and more the effect was statistically significant.

Do pregnancy, postpartum period and lactation predispose to recurrent toxoplasmic retinochoroiditis?

BACKGROUND: The aim of the study was a statistical analysis of the possible effects of pregnancy, postpartum period, and lactation on increased risk for reactivation of toxoplasmic retinochoroiditis. MATERIAL AND METHODS: A retrospective study was undertaken of the clinical records of 661 patients referred with the diagnosis of acute toxoplasmic retinochoroiditis to the Department of Zoonoses and Tropical Diseases, Medical University of Warsaw and to the Department of Ophthalmology, Medical University of Warsaw in the years 1994-2014. This group of inpatients consisted of 213 women of child-bearing age (18 to 40 years). Reactivation of toxoplasmic retinochoroiditis was observed in 24 women aged 15 to 39 years who were pregnant, in the postpartum period, or lactating. To compare the rate of the relapses in pregnant/lactating patients vs. non-pregnant/non-lactating patients, the Fisher exact test was used. Calculations were performed with WinPepi software (Abramson JH (2004) WINPEPI (PEPI-for-Windows) for epidemiologists. Epidemiologic Perspectives & Innovations, 2005, 1: 6). RESULTS: A total of 28 reactivations of toxoplasmic retinochoroiditis were observed (16 episodes in pregnancy, 4 in the postpartum period, and 8 during lactation) in 24 women aged 15 to 39 years. In 3 women, multiple episodes were reported (in early pregnancy and the postpartum period in 2 women, and during 2 pregnancies and lactation in 1 woman). Statistical analysis showed that the risk of an episode of toxoplasmic retinochoroiditis is 7.4-fold higher in pregnancy compared to the non-pregnant/non-lactating women (p<0.0001). CONCLUSIONS: Women of childbearing age with toxoplasma ocular lesions should be informed by their doctors about possible active recurrences during pregnancy and should be followed carefully by an ophthalmologist when pregnant.

ANALYSIS OF TRENDS IN LIFE EXPECTANCIES AND PER CAPITA GROSS DOMESTIC PRODUCT AS WELL AS PHARMACEUTICAL AND NON-PHARMACEUTICAL HEALTHCARE EXPENDITURES.

Life expectancy is a common measure of population health. Macro-perspective based on aggregated data makes it possible to approximate the impact of different levels of pharmaceutical expenditure on general population health status and is often used in cross-country comparisons. The aim of the study was to determine whether there are long-run relations between life expectancy, total healthcare expenditures, and pharmaceutical expenditures in OECD countries. Common trends in per capita gross domestic products (GDPs) (excluding healthcare expenditures), per capita healthcare expenditures (excluding pharmaceutical expenditures), per capita pharmaceutical expenditures, and life expectancies of women and men aged 60 and 65 were analyzed across OECD countries. Short-term effect of pharmaceutical expenditure onto life expectancy was also estimated by regressing the deviations of life expectancies from their long-term trends onto the deviations of pharmaceutical and non-pharmaceutical health expenditures, as well as GDP from their trends. The dataset was created on the basis of OECD Health Data for 34 countries and the years 1991-2010. Life expectancy variables were used as proxies for the health outcomes, whereas the pharmaceutical and healthcare expenditures represented drug and healthcare consumption, respectively. In general, both expenditures and life expectancies tended to increase in all of the analyzed countries; however, the growth rates differed across the countries. The analysis of common trends indicated the existence of common long-term trends in life expectancies and per capita GDP as well as pharmaceutical and non-pharmaceutical healthcare expenditures. However, there was no evidence that pharmaceutical expenditures provided additional information about the long-term trends in life expectancies beyond that contained in the GDP series. The analysis based on the deviations of variables from their long-term trends allowed concluding that pharmaceutical expenditures significantly influenced life expectancies in the short run. Non-pharmaceutical healthcare expenditures were found to be significant in one out of four models (for life expectancy of women aged 65), while GDPs were found to be insignificant in all four models. The results of the study indicate that there are common long-term trends in life expectancies and per capita GDP as well as pharmaceutical and non-pharmaceutical healthcare expenditures. The available data did not reveal any cause- effect relationship. Other factors, for which the systematic data were not available, may have determined the increase in life expectancy in OECD countries. Significant positive short-term relations between pharmaceutical expenditures and life expectancies in OECD countries were found. The significant short-term effect of pharmaceutical expenditures onto life expectancy means that an increase of pharmaceutical expenditures above long-term trends would lead to a temporary increase in life expectancy above its corresponding long-term trend. However, this effect would not persist as pharmaceutical expenditures and life expectancy would converge to levels determined by the long-term trends.

[The prevalence of common mental disorders in the population of adult Poles by sex and age structure - an EZOP Poland study]. / Rozpowszechnienie wybranych zaburzen psychicznych w populacji doroslych Polaków z odniesieniem do plci i struktury wieku - badanie EZOP Polska.

AIM: The article presents lifetime (LT) prevalence of common mental disorders (CMD) in accordance with the DSMIV classification, based on assessment of representative population sample of 10,081 Poles aged 18-64. METHODS: Computer based WHO CIDI3.0 was adapted for the Polish population according to WMH protocol. The survey was performed by certified and supervised interviewers. RESULTS: Out of the 18 CMDs analyzed the most common was alcohol abuse, significantly more often in males (18.6%) than in women (3.3%), (p<0.01). The second most common disorder was panic, also more frequent in women (8.5%) than in men (3.9%), (p<0.01). Similarly, depression occurred in women (4.0%) two times more often than in males (1.9%), (p<0.01). GAD, agoraphobia, panic, specific phobia (p<0.01), and dysthymia (p<0.05) were also more prevalent in women. On the other hand, alcohol abuse, alcohol and drug dependence (p<0.01), and hypomania (p<0.05) were more common in males. For most analyzed disorders significantly higher prevalence was found in the older age groups. Social phobia, specific phobias, and drug abuse occurred most often in men from the youngest group. No significant differences related to age were found for the prevalence of hypomania both in men and women. CONCLUSIONS: Indices of prevalence obtained in the EZOP Poland study differ from the indices of prevalence of mental disorders described earlier in other countries. Lower values were found in Poland for affective disorders and some anxiety disorders. Only alcohol abuse was diagnosed more often than in other studies using similar methods except Ukraine, where this disorder was diagnosed with similar frequency.

Consistency of Bordetella pertussis vaccine seed strains and potency of whole-cell pertussis vaccine still in use in Poland.

In Poland, where the wP vaccine has been used since 1960, pertussis rates increased in the mid-1990s. In 2012, the rate of pertussis recognised by surveillance was unexpectedly found to be two-fold higher than in the previous decade. Quality measures on potency and vaccine working seeds were introduced, to confirm the possible impact of manufacturing inconsistency or potency lowering on the observed increase in pertussis. Shewhart charts on potency values for lots released between 2001 and 2013 did not reveal any significant fluctuations. Working seeds of three vaccine strains used within last decade for wP manufacturing belong to the PFGE group III and were highly related. According to PFGE and SDS-PAGE data, all vaccine strains were found consistent according profiling on the genomic and protein levels. According to the sequencing data, they harboured ptxA2, ptxC1, prn1, fim2-1, fim3-1, tcfA2, ptxP1 and were assigned as MLST-2 type. Other factors apart from vaccine manufacturing inconsistency might be responsible for the increase in pertussis noted in 2012 in Poland.

[Evaluation of Bordetella pertussis strains toxicity in vitro using CHO cell lines]. / Ocena toksycznosci szczepów Bordetella pertussis z zastosowaniem linii komórkowych CHO in vitro.

INTRODUCTION: Whooping cough is still a significant disease with regular outbreaks despite the decades of mass vaccination and good immunization coverage. The aim of this study was to evaluate the capacity of Bordetella pertussis toxicity testing among strains harbouring different alleles of the pertussis toxin promoter ptxP using hamster ovary cell line CHO (Hamster Ovary). METHODS: The study assessed the limits of detection of high and low Ptx levels producing strains using a reference preparation ofpertussis toxin and B. pertussis strains that increased toxicity in vitro has been previously correlated with ptxP3 allele presence. RESULTS: The presence of the strong agglomerates on CHO cell line confirmed the higher toxicity of B. pertussis strains isolated in France. Preliminary toxicity study with use of selected strains of B. pertussis differing by ptxP1 and ptxP3 promdter alleles with respect to relevant reference preparation indicate lower toxicity of strains B. pertussis isolated in Poland. CONCLUSIONS: The toxicity measured on CHO line will be used to assess the virulence of all available B. pertussis strains isolated in Poland.

Effectiveness of experimental whole-cell pertussis vaccines in murine model.

INTRODUCTION: Since the 1990s pertussis re-emergence has been observed in many highly immunized countries. Genetic divergence between circulating B. pertussis isolates and vaccine strains has been suggested as one of the reasons responsible for the resurgence of pertussis. This divergence was observed in some studies to affect the effectiveness of pertussis vaccine when tested in murine model. In the study, using the murine intranasal challenge model we evaluated the effectiveness of four experimental wP vaccines, prepared with B. pertussis isolates belonging to different PFGE groups, in the elimination of the bacterial infection induced with mixture of the four B. pertussis isolates. METHODS: The experimental wP vaccines were prepared with clinical isolates belonging to PFGE groups V, IVγ and C, used individually or together. The mixture of four isolates classified to PFGE groups V, IVγ, III and C was used as intranasal mice challenge. The chosen strains represent PFGE groups characteristic for isolates currently circulating in Europe (PFGE groups IV and V), specific for Poland (PFGE group C) and vaccine strains of Polish wP vaccine (PFGE group III). Additionally, to study bacterial fitness, changes in the proportions of four isolates used as the challenge within the course of infection in mice lungs were monitored. RESULTS AND CONCLUSIONS: All experimental wP vaccines were found to be equally effective in eliminating B. pertussis from mice lungs. Their effectiveness was independent on PFGE group of vaccine strain. The results on bacterial fitness during mixed infections induced in the non-immunized mice found the isolate of PFGE group IVγ dominating among the other isolates used in the mixture belonging to PFGE group III, V, and C. This data might suggest that the isolates belonging to PFGE group IV, so commonly seen in Europe, might be more fitted to explore in conditions of waning immunity.

[Rescue procedures in the major trauma of upper extremities - the role of the Polish medical air rescue in the therapeutic process]. / Postepowanie ratunkowe w ciezkich urazach konczyn górnych - rola lotniczego pogotowia ratunkowego w procesie terapeutycznym.

BACKGROUND: Due to the growing use of various types of industrial and agricultural machinery, occupational accidents are among the most serious ones and quite frequently result in the permanent posttraumnatic disability of the injured person. In Poland, a replantation service has been operating since 2010. Each day, one out of six centres provides emergency replantation service accepting amputation calls from across the country. Patients qualified for replantation often need to be transported from places located even several hundred kilometres from the target hospital. MATERIAL AND METHODS: The analysis covered 174 Helicopter Emergency Medical Service (HEMS) missions and 112 interhospital transports. The data were obtained as a result of a retrospective analysis of the air and medical documentation of 23 460 missions carried out by the Polish Medical Air Rescue (Samodzielny Publiczny Zaklad Opieki Zdrowotnej Lotnicze Pogotowie Ratunkowe - SP ZOZ LPR) aircrafts in the years 2011-2013. RESULTS: In the period under study, the Polish Medical Air Rescue helicopters dressed 135 patients with upper extremity amputations at the scene and transported them to hospitals as part of HEMS missions. At the same time, SP ZOZ LPR aircrafts made 102 interhospital transports. Ninety patients were qualified for treatment in replantation service centres. The average air transport time was 76 min, while the total transport time was 172.3 min. With transport exceeding 300 kin, the average time advantage over the ground transport was approximately 1.5 h. CONCLUSIONS: In justified cases, the use of helicopters and airplanes is an optimal method of transporting patients with the major trauma to upper extremities.

The protective effect of a new absorbent incontinence design against an alkaline pH challenge on the epidermal barrier.

BACKGROUND: Incontinence-associated dermatitis (IAD) is one of the most common complications of incontinence. Improved diaper designs can minimize the occurrence of IAD. PURPOSE: To develop a novel diaper design to minimize the damaging effects of incontinence on the epidermal barrier. METHODS: An optimized diaper design was tested for surface dryness (ie, rewet), maintenance of a skin-adapted surface pH of 5.5, and ability to protect epidermal barrier function from an alkaline pH 10.7 challenge. RESULTS: The diapers released a mean (standard deviation [SD]) of 1.2 (0.2) mg/cm2 of solution under pressure after the first loading and a mean of 2.9 (1.7) mg/cm2 after the second loading. The surface pH remained between 4.5 and 5.5 over 5 hours. In healthy skin, transepidermal water loss (TEWL) increased by a mean of 3.43 (4.67) g/m2/h after the alkaline urine solution challenge with the new diaper design versus a mean of 8.38 (5.67) g/m2/h with a cellulose patch (P < .001) as a control. The mean erythema readings were 1.18 (1.30) g/m2/h for the new design and 2.56 (1.25) g/m2/h for the cellulose patches (P < .001). CONCLUSION: The new diaper design minimizes rewetting, maintains an acidic surface, and protects the epidermal barrier against an alkaline pH challenge. This design may help prevent IAD.

[The studies of elimination of nontypeable Haemophilus influenzae strains using the animal model of infection]. / Badania eliminacji nietypowalnych szczepów Haemophilus influenzae na modelu zwierzecym.

INTRODUCTION: The intranasal immunization is considered the effective method to induce immunological response in the mucosa and the model useful to develop the vaccine against otitis media due to nontypaeble Haemophilus influenzae infections. In the study, elimination of NTHi strains isolated from healthy and carrier individuals, varying with several genetic determinants, from mice nasopharynx, lungs and ears tissues and the interactions among strains during mixed infections were evaluated. METHODS: Mice were infected with single and mixture of NTHi strains previously identified as non or potentially invasive. The curves of infections were drown from the averages of log cfu/mg values obtained for nasopharynx or ears leavages or lungs homogenates coupled with standard deviation at each time point using 5 mice. The significance of the differences was confirmed using ANOVA method. RESULTS: The course of infections induced with a single noninvasive or potentially invasive strains in the mice nasopharynx, ear or lung tissues were not found to differ in respect to the level and duration. Regardless the strain used, higher elimination rates in the ear and lung tissues in comparison with nasopharynx were fund. Different rate of elimination was found in the case of mixture infections where the strain, determined in the previous study as potentially invasive, was dominating. CONCLUSION: The concurrence model among not-invasive and potentially invasive NTHi strains in the host niche was thus confirmed using in vivo model of infection.

Cell wall carbohydrates content of pathogenic Candida albicans strain morphological forms.

INTRODUCTION: The study evaluated the cell wall carbohydrates fraction in blastoconidia grown in YEPD medium at 30 degrees C and in the conglomerate of true hyphae grown in human serum at 37 degrees C. MATERIAL AND METHODS: The clinical isolate obtained from a child with widespread C. albicans infection was used in the study. The cells were broken with glass beads, centrifuged to harvest the cell wall followed by subjection to TFA hydrolysis and in the result of that released monosaccharides were detected by HPAEC-PAD. Both, serum and temperature conditions (37 degrees C) affected germination process influencing the cell wall carbohydrates content when incubation in serum was prolonged from 1 to 18 h. RESULTS: The mannan content of blastoconidia was almost twofold higher compared to filamentous forms (149.25 +/- 299.24 vs 77.26 +/- 122.07). The glucan content was threefold lower in blastoconidia compared to hyphae (251.86 +/- 243.44 vs 755.81 +/- 1299.30). The chitin level was fourfold lower in blastoconidia compared to filaments (23.86 +/- 54.09 vs 106.29 +/- 170.12). The reason for the differences in the carbohydrates content may be related to type of morphology induced in different environmental conditions. Among tested carbohydrates, glucan appeared to be present in appreciably larger amounts in both tested morphological fractions. The ultrastructure of the blastoconidial cell wall revealed striking differences compared to the hyphae indicating the carbohydrates content alterations for wall assembly during hyphal growth at alkaline pH and temp. 37 degrees C. CONCLUSIONS: The study provided evidence for the relationship between morphogenesis, cell-cell adhesion induced by serum and changes in the level of carbohydrates content.