Expression of Inflammation Depending on the Stage of Cervical Cancer.

Background and Objectives: Cervical cancer (CC) remains a major public health problem, ranking as the fourth most common cause of cancer incidence and mortality in women globally. The development of CC is believed to be closely related to chronic inflammation. Thus, we aimed to evaluate the expression of systemic inflammation in patients with CC and to determine the threshold prognostic value of the systemic inflammation markers for CC and its advanced stage. Materials and Methods: 182 participants were recruited: 94 histology-proven patient with CC and 88 healthy women with NILM confirmed by liquid-based cytology test. The pre-treatment serum concentrations of cytokines, including IFN-ß, IFN-γ, IL-1ß, IL-2, IL-6, IL-10, IL-12p70, LCN2, TREM-1, and TNF-α, were determined for all study patients. Results: The odds ratio (OR) of having IL-6 concentration >17.4 pg/mL in the CC group compared to control patients was 11.4 (95% CI: 4.897-26.684); that of having TREM-1 concentration >355.6 pg/mL was 5.9 (95% CI: 2.257-15.767); and that of having LCN2 concentration >23,721.5 pg/mL was 3.4 (95% CI: 1.455-8.166). The odds ratio (OR) of having IL-6 concentration >28.7 pg/mL in advanced-stage CC (III-IV stage) compared to early-stage CC (I-II stage) was 2.921 (95% CI: 1.06-8.045), and that of having LCN2 concentration >25,640.0 pg/mL was 4.815 (95% CI: 1.78-13.026). Conclusions: The pre-treatment serum inflammation markers IL-6, TREM-1, and LCN2 at specified levels could be used as predictors of cervical cancer, and IL-6 and LCN2 as predictors of an increased chance of advanced-stage (III-IV stages) cervical cancer. Patients with cervical cancer had expressed systemic inflammation, and expression of inflammation elevated the chance of having CC and advanced-stage disease.

Human Placental Mesenchymal Stem Cells and Derived Extracellular Vesicles Ameliorate Lung Injury in Acute Respiratory Distress Syndrome Murine Model.

This study investigates the therapeutic potential of human placental mesenchymal stem cells (P-MSCs) and their extracellular vesicles (EVs) in a murine model of acute respiratory distress syndrome (ARDS), a condition with growing relevance due to its association with severe COVID-19. We induced ARDS-like lung injury in mice using intranasal LPS instillation and evaluated histological changes, neutrophil accumulation via immunohistochemistry, bronchoalveolar lavage fluid cell count, total protein, and cytokine concentration, as well as lung gene expression changes at three time points: 24, 72, and 168 h. We found that both P-MSCs and EV treatments reduced the histological evidence of lung injury, decreased neutrophil infiltration, and improved alveolar barrier integrity. Analyses of cytokines and gene expression revealed that both treatments accelerated inflammation resolution in lung tissue. Biodistribution studies indicated negligible cell engraftment, suggesting that intraperitoneal P-MSC therapy functions mostly through soluble factors. Overall, both P-MSC and EV therapy ameliorated LPS-induced lung injury. Notably, at the tested dose, EV therapy was more effective than P-MSCs in reducing most aspects of lung injury.

Association between AHR Expression and Immune Dysregulation in Pancreatic Ductal Adenocarcinoma: Insights from Comprehensive Immune Profiling of Peripheral Blood Mononuclear Cells.

Pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDAC), has an immune suppressive environment that allows tumour cells to evade the immune system. The aryl-hydrocarbon receptor (AHR) is a transcription factor that can be activated by certain exo/endo ligands, including kynurenine (KYN) and other tryptophan metabolites. Once activated, AHR regulates the expression of various genes involved in immune responses and inflammation. Previous studies have shown that AHR activation in PDAC can have both pro-tumorigenic and anti-tumorigenic effects, depending on the context. It can promote tumour growth and immune evasion by suppressing anti-tumour immune responses or induce anti-tumour effects by enhancing immune cell function. In this study involving 30 PDAC patients and 30 healthy individuals, peripheral blood samples were analysed. PDAC patients were categorized into Low (12 patients) and High/Medium (18 patients) AHR groups based on gene expression in peripheral blood mononuclear cells (PBMCs). The Low AHR group showed distinct immune characteristics, including increased levels of immune-suppressive proteins such as PDL1, as well as alterations in lymphocyte and monocyte subtypes. Functional assays demonstrated changes in phagocytosis, nitric oxide production, and the expression of cytokines IL-1, IL-6, and IL-10. These findings indicate that AHR's expression level has a crucial role in immune dysregulation in PDAC and could be a potential target for early diagnostics and personalised therapeutics.

Antiphospholipid antibodies and the risk of thrombosis in myeloproliferative neoplasms.

The morbidity and mortality of BCR-ABL-negative myeloproliferative neoplasia (MPN) patients is highly dependent on thrombosis that may be affected by antiphospholipid antibodies (aPLA) and lupus anticoagulant. Our aim was to evaluate the association of the aPLA together with platelet receptor glycoprotein (GP) Ia/IIa c.807C>T CT/TT genotypes and thrombotic complications in patients with MPNs. The study included 108 patients with BCR-ABL-negative MPN with data of previous thrombosis. Two different screening and one confirmatory test for the lupus anticoagulant were performed. Thrombotic complications were present in 59 (54.6%) subjects. aPLA were more frequently found in MPN patients with thrombosis vs no thrombosis (25.4 and 6.1%; p = 0.007). MPN patients with arterial thrombosis were more frequently positive for aPLA vs no arterial thrombosis (38.8 and 11.9%; p = 0.001). aPLA were more frequently found in patients with cerebrovascular events vs other arterial thrombotic complications or no thrombosis, respectively (39.3, 6.1, and 12.9%; p < 0.001). MPN patients with thrombosis were more frequently positive with aPLA and had platelet receptor GP Ia/IIa c.807C>T CT/TT genotypes compared to MPN patients without thrombosis (18.6 and 2.0%; p = 0.006). aPLA alone or with coexistence with platelet receptor GP Ia/IIa c.807C>T CT/TT polymorphism could be associated with thrombotic complications in patients with MPN.

Blood biomarkers in early bacterial infection and sepsis diagnostics in feverish young children.

BACKGROUND AND OBJECTIVES: While most feverish children have self-limiting diseases, 5-10% develop a serious and potentially life-threatening bacterial infection (BI). Due to potential risk, prompt recognition of BI and sepsis in the pediatric emergency department (PED) remains a clinical priority. The aim of the study was to evaluate the role of certain cytokines and chemokines separately and in combination with routine blood tests in early BI and sepsis diagnostics at PED. MATERIALS AND METHODS: We prospectively studied children younger than 5 presenting to the PED with fever lasting for under 12 hours with high risk for serious illness. Clinical data, routine blood analysis, and inflammatory cytokine and chemokine panels were evaluated for their diagnostic abilities. Two separate analyses were carried out on the patients' data: one contrasting BI and viral infection (VI) groups, the other comparing septic and non-septic patients. RESULTS: The sample comprised 70 patients (40% with BI). IL-2 was found to be the most specific biomarker to identify BI with specificity of 100%. The best discriminative ability was demonstrated by combining IL-2, IL-6, CRP, WBC, and neutrophil count: AUC 0.942 (95% Cl 0.859-0.984). IL-10 exhibited a greater AUC (0.837. 95% CI: 0.730-0.915 p<0.05) than CRP (0.807. 95% CI: 0.695-0.895 p<0.05) when predicting sepsis and showed high specificity (98%) and moderate sensitivity (75%). CONCLUSIONS: IL-6 and IL-2 could increase the diagnostic ability of routine blood tests for predicting BI, as IL-10 raises specificity for recognizing sepsis in the early hours of disease onset.

Expression of Interleukin-17, Tumor Necrosis Factor-Alpha, and Matrix Metalloproteinase-8 in Patients with Chronic Peri-Implant Mucositis.

BACKGROUND The present study aimed to evaluate whether non-surgical treatment interferes with clinical parameters and local patterns of osteo-immunoinflammatory mediators (IL-17 and TNF-alpha) and matrix metalloproteinase-8 (MMP-8) that are found in peri-implant crevicular fluid (PICF) and biofilms during the progression of peri-implant mucositis. MATERIAL AND METHODS We selected 30 patients with peri-implant caused mucositis before (MP) and after treatment (TP) and 30 healthy people (HP) for the analysis of IL-17, TNF-alpha cytokine, and MMP-8 production in PICF and for analysis of colonization dynamics of periodontopathogenic bacteria in supra- and subgingival plaque samples. The levels of IL-17 and MMP-8 concentrations in samples were assayed by enzymatic immunosorbent assay (ELISA) and TNF-alpha levels were determined by enzyme amplified sensitivity immunoassay (EASIA) method in PICF. The micro-IDent test was used to detect 11 species of periodontopathogenic bacteria in subgingival biofilm. RESULTS We found significantly (P<0.001) higher levels of IL-17, TNF-alpha, and MMP-8 in the PICF of the MP and TP groups in comparison to the HP group. A significant association was found in MP associated with Parvimonas micra, as TNF-alpha in PICF was significantly higher (P=0.034) than in patients without Parvimonas micra. TNF-alpha levels in the samples of PICF showed a moderate correlation with clinical parameters, including plaque index (PI) (P=0.007) and MMP-8 levels (P=0.001), in the MP group. CONCLUSIONS Assessment of levels of inflammatory cytokines in PICF can aid in the identification of peri-implant mucositis, which can assist in early diagnosis, prevention, and treatment.

Residual effects of short-term whole-body cold-water immersion on the cytokine profile, white blood cell count, and blood markers of stress.

Background: One of the most challenging environmental extremes is immersion in cold/icy water, and consequent common assumption is that even a brief exposure to cold can lead to cold-related illnesses. The increase in the concentrations of the stress hormones cortisol, epinephrine (Epi), and norepinephrine (NE) in response to acute cold stress are thought to suppress the release of proinflammatory cytokines. No previous study has explored the residual consequences of whole-body short-term cold-water immersion (CWI; 14 °C for 10 min) on the immune response in healthy non-acclimated young adult men (aged 20-30 years).Materials and methods: In the current study, we tested the hypothesis that short-term acute whole-body CWI would induce high blood levels of cortisol, NE, and Epi, which in turn would increase circulating leukocyte numbers and delay the production of proinflammatory cytokines (tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and IL-6). Results: Short-term whole-body CWI produced a stressful physiological reaction, as manifested by hyperventilation and increased muscle shivering, metabolic heat production, and heart rate. CWI also induced the marked release of the stress hormones Epi, NE, and cortisol. The change in IL-6 concentration after CWI was delayed and TNF-α production was decreased, but IL-1ß was not affected within 48 h after CWI. A delayed increase in neutrophil percentage and decrease in lymphocyte percentage occurred after CWI.Conclusion: These findings suggest that, even though CWI caused changes in stress and immune markers, the participants showed no predisposition to symptoms of the common cold within 48 h after CWI.

Chronic Rhinosinusitis with Nasal Polyps: Age and Disease Severity Differences in the Levels of Inflammatory Markers.

Background and objectives: The aim of our study was to analyze the concentrations of inflammatory markers in the nasal tissue of patients with chronic rhinosinusitis with nasal polyps (CRSwNPs) and controls of different age groups, as well as to find associations between age, inflammation development, and NPs. Materials and methods: Patients were divided into two groups-patients with CRSwNPs and control subjects who had nasal surgery for another reason beside CRS. Our analysis was performed across three different age groups (18-30 years, 31-50 years, and 51 years and more). Tissue biopsies from the sinus cavity for all study participants were taken and frozen at -80 °C, until use. The concentrations of IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-13, IL-21, and IL-22, were quantified using a magnetic bead-based multiplex assay. Results: In the group aged 18-30 years, the levels of inflammatory markers IL-1, IL-2, IL-5, and IL-22 were significantly higher in patients with CRSwNPs than the control subjects. Among patients aged 31-50 years, significantly higher concentrations of IL-2, IL-4, IL-5, and IL-22 were recorded in patients with CRSwNPs, as compared to the control subjects. In the oldest group (aged 51 years and more), patients with CRSwNPs had significantly higher concentrations of IL-2, IL-4, and IL-22, as compared to the control group. In the CRSwNP group, only the concentration of IL-21 was significantly higher among patients aged 31-50 years, as compared with those aged 51 years and older (p = 0.013). Conclusions: IL-2 and IL-22 levels were significantly higher in patients with CRSwNP than the control, across all age groups. Only the concentration of IL-21 was higher among patients with CRSwNP in the middle age group, as compared to the oldest group. IL-2, IL-4, and IL-22 levels correlated with the severity of CRSwNPs. Elevated concentrations of IL-2, IL-4, and IL-22 were determined in patients' groups with higher sinonasal outcome test (SNOT-22) scores, pointing to more severe clinical symptoms.

Recovering body temperature from acute cold stress is associated with delayed proinflammatory cytokine production in vivo.

A poor outcome of whole-body hypothermia often results from a late complication, rather than from acute effects of hypothermia. A low body (cell) temperature or the increase in the concentrations of the stress hormones cortisol, epinephrine, and norepinephrine in response to acute cold stress have been proposed as potent proinflammatory cytokine suppressant. In the current study, we tested the hypothesis that the recovery of body temperature from a whole-body intermittent cold-water immersion (CWI, at 13-14 °C for a total 170 min) is associated with a delayed response of proinflammatory cytokines in young healthy men. Our results revealed a delay in the increase in the proinflammatory interleukin 6 and interleukin 1ß cytokines after the CWI, which paralleled the changes in cortisol, epinephrine, norepinephrine, and body temperature. CWI decreased tumor necrosis factor α (TNF-α) immediately and 1 h after the CWI. Although TNF-α had recovered to the pre-immersion level at 2 h after CWI, its natural circadian cycle kinetics was disrupted until 12 h after the CWI. Furthermore, we showed that CWI strongly modified the white blood cell counts, with changes reaching a peak between 1 and 2 h after the CWI.

Local inflammatory marker production in Lithuanian patients with chronic rhinosinusitis with nasal polyps.

There are two clinical subtypes of chronic rhinosinusitis (CRS): chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP). The aim of the study here was to determine the levels of invasive inflammatory markers in nasal mucosa samples taken from CRSwNP patients during the surgery and to identify markers that could serve as targets for potential clinical and therapeutic interventions. The study was carried out in 59 patients with proven CRSwNP and a control group consisting of 52 healthy individuals. Concentrations of the inflammatory markers of interest were determined using a LuminexR Assay multiplex kit. The data obtained indicated that levels of inflammatory cytokines interleukin (IL)-2, -4, -5, -7, -12, -17 and -22 were all significantly higher in the nasal polyps (NP) than those in the mucosa of control participants. No differences were seen between the study groups for IL -6, -10, -13, -21 and interferon (IFN)-γ. OR (Odds Ratio) analyses confirmed that elevations in mucosal levels of IL-2, -4, -5, -7, -12, -17, and -22 were likely immune markers of CRSwNP. In conclusion, the present study demonstrated that IL-2, -4, -12 and -22 may be important in the etiopathogenesis of CRSwNP; as markers, each show moderate sensitivity, but high specificity in the Lithuanian population. IL-17 had good sensitivity, but low specificity in the CRSwNP patients.

Identification and Tracking of Antiviral Drug Combinations.

Combination therapies have become a standard for the treatment for HIV and hepatitis C virus (HCV) infections. They are advantageous over monotherapies due to better efficacy, reduced toxicity, as well as the ability to prevent the development of resistant viral strains and to treat viral co-infections. Here, we identify new synergistic combinations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), echovirus 1 (EV1), hepatitis C virus (HCV) and human immunodeficiency virus 1 (HIV-1) in vitro. We observed synergistic activity of nelfinavir with convalescent serum and with purified neutralizing antibody 23G7 against SARS-CoV-2 in human lung epithelial Calu-3 cells. We also demonstrated synergistic activity of nelfinavir with EIDD-2801 or remdesivir in Calu-3 cells. In addition, we showed synergistic activity of vemurafenib with emetine, homoharringtonine, anisomycin, or cycloheximide against EV1 infection in human lung epithelial A549 cells. We also found that combinations of sofosbuvir with brequinar or niclosamide are synergistic against HCV infection in hepatocyte-derived Huh-7.5 cells, and that combinations of monensin with lamivudine or tenofovir are synergistic against HIV-1 infection in human cervical TZM-bl cells. These results indicate that synergy is achieved when a virus-directed antiviral is combined with another virus- or host-directed agent. Finally, we present an online resource that summarizes novel and known antiviral drug combinations and their developmental status.

Interleukin-10 and Interleukin-1ß Cytokines Expression in Leukocytes of Patients with Chronic Peri-Mucositis.

BACKGROUND The purpose of the present research is to analyze the effect of polyphenols and flavonoids substrat (PFS) from plants Calendula officinalis, Salvia fruticosa, Achillea millefolium, and propolis as immunomodulatory in the production of interleukin (IL)-1ß and IL-10 in peripheral blood leukocytes medium (PBLM) in patients who were diagnosed with mucositis of peri-implant tissue compared to patients with healthy implant tissue. It was hypothesized that IL-1ß and IL-10 contribute to the inflammation processes noticed in the diseases of peri-implant tissues. MATERIAL AND METHODS Sixty non-smoking patients were included in this study: patients with healthy implants (HP group) and patients with peri-implant mucositis (MP group). Peri-mucositis was diagnosed by radiologic and clinical examination. The PBLM from MP were treated with PFS at various concentrations. The levels of IL-10 and IL-1ß excreted by the PBLM stimulated and unstimulated with viable Porphyromonas gingivalis test-tube were committed by the enzyme amplified immunoassay sensitivity method. RESULTS Unstimulated and stimulated PBLM and treatment with 5.0 mg/mL or 10.0 mg/mL of PFS in the MP group produced significantly higher levels IL-10 (P<0.001) that analogous mediums of the HP group. The levels of IL-1ß decreased more considerably in the stimulated PBLM of the MP group than in those of HP group (P<0.001) after the treatment with PFS at only 10.0 mg/mL concentration. CONCLUSIONS Theses results suggest that the solution of PFS might offer a new potential for the development of a new therapeutic path to prevent and treat peri-implant mucositis.

Coagulation System Disorders and Thrombosis Prophylaxis During Laparoscopic Fundoplications.

BACKGROUND: The aim of this study was to assess and recommend the optimal deep vein thrombosis (DVT) prophylaxis regimen during and after laparoscopic fundoplication according to the blood coagulation disorders and the rate of DVT in 2 patient groups, receiving different DVT prophylaxis regimens. MATERIALS AND METHODS: This was a prospective randomized, single-center clinical study. The study population, 121 patients, were divided into 2 groups: group I received low-molecular-weight heparin 12 hours before the operation; group II received low-molecular-weight heparin only 1 hour before the laparoscopic fundoplication. Both groups received intermittent pneumatic compression during the entire procedure. Bilateral Doppler ultrasound to exclude DVT was performed before the surgery. Venous phase computed tomographic images were acquired from the ankle to the iliac tubercles on the third postoperative day to determine the presence and location of DVT. Hypercoagulation state was assessed by measuring the prothrombin fragment F1+2 (F1+2), the thrombin-antithrombin complex (TAT), and tissue factor microparticles activity (MP-TF) in plasma. The hypocoagulation effect was evaluated by measuring plasma free tissue factor pathway inhibitor (fTFPI). RESULTS: F1+2, TAT, and MP-TF indexes increased significantly, whereas fTFPI levels decreased significantly during and after laparoscopic fundoplication, when molecular-weight heparin was administered 12 hours before the operation. Computed tomography venography revealed peroneal vein thrombosis in 2 group I patients on the third postoperative day. Total postsurgical DVT frequency was 1.65%: 3.6% in group I, with no DVT in group II. CONCLUSION: Molecular-weight heparin and intraoperative intermittent pneumatic compression controls the hypercoagulation effect more efficiently when it is administered 1 hour before surgery: it causes significant reduction of F1+2, TAT, and MP-TF indexes and significant increases of fTFPI levels during and after laparoscopic fundoplication.

Early Diagnosis and Prognostic Value of Acute Kidney Injury in Critically Ill Patients.

Background and objectives: In hospitalized children, acute kidney injury (AKI) remains to be a frequent and serious condition, associated with increased patient mortality and morbidity. Identifying early biomarkers of AKI and patient groups at the risk of developing AKI is of crucial importance in current clinical practice. Specific human protein urinary neutrophil gelatinase-associated lipocalin (uNGAL) and interleukin 18 (uIL-18) levels have been reported to peak specifically at the early stages of AKI before a rise in serum creatinine (sCr). Therefore, the aim of our study was to determine changes in uNGAL and uIL-18 levels among critically ill children and to identify the patient groups at the highest risk of developing AKI. Materials and methods: This single-center prospective observational study included 107 critically ill children aged from 1 month to 18 years, who were treated in the Pediatric Intensive Care Unit (PICU) of Lithuanian University of Health Sciences Hospital Kauno Klinikos from 1 December 2013, to 30 November 2016. The patients were divided into two groups: those who did not develop AKI (Group 1) and those who developed AKI (Group 2). Results: A total of 68 (63.6%) boys and 39 (36.4%) girls were enrolled in the study. The mean age of the patients was 101.30 ± 75.90 months. The mean length of stay in PICU and hospital was 7.91 ± 11.07 and 31.29 ± 39.09 days, respectively. A total of 32 (29.9%) children developed AKI. Of them, 29 (90.6%) cases of AKI were documented within the first three days from admission to hospital. In all cases, AKI was caused by diseases of non-renal origin. There was a significant association between the uNGAL level and AKI between Groups 1 and 2 both on day 1 (p = 0.04) and day 3 (p = 0.018). Differences in uNGAL normalized to creatinine in the urine (uCr) (uNGAL/uCr) between the groups on days 1 and 3 were also statistically significant (p = 0.007 and p = 0.015, respectively). uNGAL was found to be a good prognostic marker. No significant associations between uIL-18 or Uil-18/uCr and development of AKI were found. However, the uIL-18 level of >69.24 pg/mL during the first 24 hours was associated with an eightfold greater risk of AKI progression (OR = 8.33, 95% CI = 1.39-49.87, p = 0.023). The AUC for uIL-18 was 73.4% with a sensitivity of 62.59% and a specificity of 83.3%. Age of <20 months, Pediatric Index of Mortality 2 (PIM2) score of >2.5% on admission to the PICU, multiple organ dysfunction syndrome with dysfunction of three and more organ systems, PICU length of stay more than three days, and length of mechanical ventilation of >five days were associated with a greater risk of developing AKI. Conclusions: Significant risk factors for AKI were age of <20 months, PIM2 score of >2.5% on admission to the PICU, multiple organ dysfunction syndrome with dysfunction of 3 and more organ systems, PICU length of stay of more than three days, and length of mechanical ventilation of > five days. uNGAL was identified as a good prognostic marker of AKI. On admission to PICU, uNGAL should be measured within the first three days in patients at the risk of developing AKI. The uIL-18 level on the first day was found to be as a biomarker predicting the progression of AKI.

Effects of severe whole-body hyperthermia on ovarian hormone and extracellular Hsp72 responses in young adult women.

Background: Although acute thermal stress appears to be one of the most effective stressors that increase the intra- and extracellular concentrations of heat shock protein 72 (Hsp72), 17ß-estradiol has been shown to inhibit heat-induced Hsp72 expression. Materials and Methods: To determine whether severe whole-body hyperthermia (increase in rectal temperature up to 39.5 °C) induced by lower-body heating is a sufficient stimulus to modulate hormonal (17ß-estradiol, progesterone, prolactin, epinephrine, and norepinephrine) and extracellular Hsp72 responses, we investigated young adult women (21 ± 1 yr). Results and Conclusions: In the present study, we show that a severe whole-body hyperthermia (increase in rectal temperature of approximately 2.6 °C and heart rate of approximately 80 bpm from baseline) was sufficient to increase 17ß-estradiol, progesterone, and prolactin and catecholamine norepinephrine concentration. Moreover, we show that the concentration of extracellular Hsp72 and catecholamine epinephrine were not affected by severe whole-body hyperthermia in young adult women. From the functional point of view, expression of ovarian hormones induced by passive heat stress may have therapeutic potential for young adult women in, for example, estrogen treatment and overall women's health.

Low Temperature and Low UV Indexes Correlated with Peaks of Influenza Virus Activity in Northern Europe during 2010⁻2018.

With the increasing pace of global warming, it is important to understand the role of meteorological factors in influenza virus (IV) epidemics. In this study, we investigated the impact of temperature, UV index, humidity, wind speed, atmospheric pressure, and precipitation on IV activity in Norway, Sweden, Finland, Estonia, Latvia and Lithuania during 2010⁻2018. Both correlation and machine learning analyses revealed that low temperature and UV indexes were the most predictive meteorological factors for IV epidemics in Northern Europe. Our in vitro experiments confirmed that low temperature and UV radiation preserved IV infectivity. Associations between these meteorological factors and IV activity could improve surveillance and promote development of accurate predictive models for future influenza outbreaks in the region.

Alterations of conjunctival glycocalyx and microcirculation in non-septic critically ill patients.

As of now the relationship between glycocalyx degradation and microcirculatory perfusion abnormalities in non-septic critical ill patients is unclear. In addition, conjunctival sidestream dark field-imaging for the purpose of glycocalyx thickness estimation has never been performed. We aimed to investigate whether changes in glycocalyx thickness in non-septic patients are associated with microcirculatory alterations in conjunctival and sublingual mucosa. In this single-centre prospective observational study, using techniques for direct in-vivo observation of the microcirculation, we performed a single measurement of microcirculatory perfusion parameters and visualized glycocalyx thickness in both ocular conjunctiva and sublingual mucosa in mixed cardio surgical (n = 18) and neurocritical patients (n = 27) and compared these data with age-matched healthy controls (n = 20). In addition we measured systemic syndecan-1 levels. In the sublingual and conjunctival region we observed a significant increase of the perfused boundary region (PBR) in both neuro-critical and cardiac surgical ICU patients, compared to controls. There was a significant increase of syndecan-1 in ICU patients comparing with controls and in cardiac patients comparing with neurological (120.0[71.0-189.6] vs. 18.0[7.2-40.7], p < 0.05). We detected a weak correlation between syndecan-1 and sublingual PBR but no correlations between global glycocalyx damage and conjuctival glycocalyx thickness. We found significantly lower perfused vessel density (PVD) of small vessels in sublingual mucosa in patients after cardiac surgery in comparison with healthy subjects. In neuro-critical, but not cardiac surgery patients conjunctival TVD and PVD of small vessels were found to be significantly lower in comparison with controls.

Factors associated with sputum culture conversion in patients with pulmonary tuberculosis.

OBJECTIVE: The aim of this study was to determine what factors are associated with sputum culture conversion after 1 month of tuberculosis (TB) treatment. MATERIALS AND METHODS: A total of 52 patients with new drug susceptible pulmonary TB were included in the study. Patients completed St. George respiratory questionnaire (SGRQ), they were asked about smoking, alcohol use, living conditions and education. Body mass index (BMI) measurements, laboratory tests (C reactive protein [CRP], vitamin D, albumin) were performed, and chest X-ray was done. After 1 month of treatment sputum culture was repeated. RESULTS: Culture conversion after 1 month of treatment was found in 38.5% cases. None of investigated social factors appeared to have an effect on conversion, but worse overall health status (as reported in SGRQ) and longer duration of tobacco smoking were detected in the "no conversion" group. Concentrations of albumin, CRP, X-ray score and the time it took Mycobacterium tuberculosis culture to grow also differed. Patients who scored 30 or more on SGRQ were more than 7 times as likely to have no conversion. However, the most important factor predicting sputum culture conversion was sputum smear grade at the beginning of treatment: patients with grade of 2+ or more had more than 20-fold higher relative risk for no conversion. Using receiver operating characteristic curve analysis, we also developed a risk score for no conversion. CONCLUSIONS: The most important factors in predicting sputum culture conversion after 1 month of treatment were grades of acid-fast bacilli in sputum smears at time of diagnosis and scores of SGRQ.

Section's osseous slice biopsy during major amputation of lower extremity: preliminary results of prospective cohort study.

BACKGROUND: The purpose of this cohort study was to assess the incidence of positive cultures in section's osseous slice biopsy (SOB) taken at the level of major limb amputation. In case of positive cultures we sought whether the microorganisms present in SOB could take origin from the primary infection site necessitating the amputation. The impact of diabetes on culture results was also investigated. METHODS: This prospective cohort study, which aimed to confirm the results of the pilot study, analysed patients who underwent major limb amputation between 2012 and 2013 in three Lithuanian hospitals. SOBs at the amputation site (surgical bone biopsies) and percutaneous bone biopsies of the distal site were performed simultaneously during limb amputation. Tissue cultures were analysed by microbiologists, and species along with antibiograms were reported. Histopathological assessment and bacterial typing were also evaluated. A positive culture was defined as the identification of at least 1 bacteria not belonging to the skin flora, at least 2 bacteria belonging to the skin flora with the same antibiotic susceptibility profiles or the same bacteria belonging to the skin flora in two different sites. Fisher's exact test and Student's test were used to compare the populations and the microbiological results. The statistical significance level was set at P < 0.05. RESULTS: Sixty-nine patients (35 males/34 females), mean age 68.7 (S = 13.6) years, including 21 (30.4%) with diabetes underwent the major limb amputation. Forty-five amputations (65.2%) were done above the knee. In total, 207 SOBs and 207 percutaneous distal site biopsies were studied. SOB cultures were positive in 11 (15.9%) cases. In 5 (45.5%) cases the same microorganisms were identified in both SOB and distal biopsy cultures. No association between culture results and presence of diabetes was identified. CONCLUSIONS: Our results suggest that, independently of the diabetes status, foot infection may silently spread along the bone and can achieve the site of major limb amputation. Additional investigations aiming to confirm this hypothesis and to evaluate a prognostic value are in progress.

Two strategies for the acute response to cold exposure but one strategy for the response to heat stress.

PURPOSE: The main aim of this study was to compare physiological and psychological reactions to heat stress between people who exhibited fast cooling (FC, n = 20) or slow cooling (SC; n = 20) responses to 14 °C cold water immersion. METHODS: Forty healthy young men (19-25 years old) were recruited to this study based on their tolerance to cold exposure (FC versus SC). The heat stress was induced using immersion in bath water at 43-44 °C. Motor and cognitive performance, immune variables, markers of hypothalamic-pituitary-adrenal axis activity (i.e. stress hormone concentrations), and autonomic nervous system activity were monitored. RESULTS: In the FC group, time to warm the body from a resting rectal temperature (Tre) of 37.1 ± 0.2 °C before warming to 39.5 °C was 63.7 ± 22.4 min. In the SC group, the time to warm the body from a Tre 37.1 ± 0.3 °C before warming to 39.5 °C was 67.2 ± 13.8 min (p > 0.05 between groups). The physiological stress index (PSI) after warming was 8.0 ± 0.6 and 8.2 ± 1.0 in the FC and SC groups, respectively (p > 0.05 between groups). During warming, the changes in subjective indicators of heat stress did not differ significantly between the FC (7.4 ± 0.5) and SC (7.1 ± 1.1) groups, respectively. CONCLUSION: The increase in cortisol, epinephrine, norepinephrine, and corticosterone concentrations after passive body heating did not differ between the FC and SC groups. Heat stress did not change indicators of innate and specific immunity in the FC or the SC group. An interesting finding was that heat stress did not affect motor and cognitive function in either group, although central fatigue during 1-min maximal voluntary contraction increased after heat stress in both groups.