Real-time in vivo ROS monitoring with luminescent nanoparticles reveals skin inflammation dynamics.

Reactive oxygen species (ROS) are key regulators in numerous pathological contexts, including cancer or inflammation. Their role is complex, which justifies the need for methods enabling their quantitative and time-resolved monitoring in vivo, in the perspective to profile tissues of individual patients. However, current ROS detection methods do not provide these features. Here, we propose a new method based on the imaging of lanthanide-ion nanoparticles (GdVO4:Eu), whose photoluminescence is modulated by the surrounding ROS concentration. We monitored their luminescence after intradermic injection in a mouse ear submitted to an inflammation-inducing topical stimulus. Based on this approach, we quantified the ROS concentration after inflammation induction and identified a two-step kinetics of ROS production, which may be attributed to the response of resident immune cells and their further recruitment at the inflammation locus.

Inability to work following COVID-19 vaccination-a relevant aspect for future booster vaccinations.

OBJECTIVES: COVID-19 vaccination is a key prevention strategy to reduce the spread and severity of SARS-CoV-2 infections. However, vaccine-related inability to work among healthcare workers (HCWs) could overstrain healthcare systems. STUDY DESIGN: The study presented was conducted as part of the prospective CoVacSer cohort study. METHODS: This study examined sick leave and intake of pro re nata medication after the first, second, and third COVID-19 vaccination in HCWs. Data were collected by using an electronic questionnaire. RESULTS: Among 1704 HCWs enrolled, 595 (34.9%) HCWs were on sick leave following at least one COVID-19 vaccination, leading to a total number of 1550 sick days. Both the absolute sick days and the rate of HCWs on sick leave significantly increased with each subsequent vaccination. Comparing BNT162b2mRNA and mRNA-1273, the difference in sick leave was not significant after the second dose, but mRNA-1273 induced a significantly longer and more frequent sick leave after the third. CONCLUSION: In the light of further COVID-19 infection waves and booster vaccinations, there is a risk of additional staff shortages due to postvaccination inability to work, which could negatively impact the already strained healthcare system and jeopardise patient care. These findings will aid further vaccination campaigns to minimise the impact of staff absences on the healthcare system.

Cervical vertebral column morphology in patients with obstructive sleep apnoea assessed using lateral cephalograms and cone beam CT. A comparative study.

OBJECTIVES: Few studies have described morphological deviations in obstructive sleep apnoea (OSA) patients on two-dimensional (2D) lateral cephalograms, and the reliability of 2D radiographs has been discussed. The objective is to describe the morphology of the cervical vertebral column on cone beam CT (CBCT) in adult patients with OSA and to compare 2D lateral cephalograms with three-dimensional (3D) CBCT images. METHODS: For all 57 OSA patients, the cervical vertebral column morphology was evaluated on lateral cephalograms and CBCT images and compared according to fusion anomalies and posterior arch deficiency. RESULTS: The CBCT assessment showed that 21.1% had fusion anomalies of the cervical column, i.e. fusion between two cervical vertebrae (10.5%), block fusions (8.8%) or occipitalization (1.8%). Posterior arch deficiency occurred in 14% as partial cleft of C1 and in 3.5% in combination with block fusions. The agreement between the occurrence of morphological deviations in the cervical vertebral column between lateral cephalograms and CBCT images showed good agreement (κ = 0.64). CONCLUSIONS: Prevalence and pattern in the cervical column morphology have now been confirmed on CBCT. The occurrence of morphological deviations in the cervical vertebral column showed good agreement between lateral cephalograms and CBCT images. This indicates that 2D lateral cephalograms (already available after indication in connection with, e.g. treatment planning) are sufficient for identifying morphological deviations in the cervical vertebral column. For a more accurate diagnosis and location of the deviations, CBCT is required. New 3D methods will suggest a need for new detailed characterization and division of deviations in cervical vertebral column morphology.

Immunohistochemical analysis of hepatic ganglioside distribution following a partial hepatectomy and exposure to different hyperbaric oxygen treatments.

Ganglioside GM3(Neu5Ac) expression is highly increased in liver 54h following 15% partial hepatectomy in pre-operatively oxygenated rats. GM3(Neu5Gc), GM2, GalNAc-GM1b and gangliosides of the neolacto-series are less affected. GM3(Neu5Ac) is a potent inhibitor of epidermal growth factor signaling. Since GM3(Neu5Ac) growth inhibitory effect depends on its cellular localization, the aim of this study was to detect ganglioside cellular localization during liver regeneration. The experiment was performed using the same rat model which previously showed increased ganglioside expression and more efficient liver regeneration. Frozen sections of liver were analyzed using confocal microscopy after labeling for binding of five ganglioside-specific antibodies, with or without hepatocyte membrane permeabilization. Ganglioside precursors, ceramide (Cer), monohexaosylceramide and lactosylceramide (LacCer) were determined by high-performance thin-layer chromatography. Apoptosis was assessed by fluorescein-dUTP end-labeling of fragmented DNA. Liver of pre-operative oxygenated rats showed high perinuclear labeling of GM3(Neu5Ac) which was absent in post-operative oxygenated and control animals. In the same group, Cer content was lower, monohexaosylceramide and LacCer were absent, and content of apoptotic cells was significantly the lowest, compared to other groups examined (F=20.36, p=0.0001). These findings indicate that ganglioside GM3(Neu5Ac) may be involved in mediation of beneficial effects of pre-operatively oxygenation during the liver regeneration.

Effect of erythromycin on the absorption of fexofenadine in the jejunum, ileum and colon determined using local intubation in healthy volunteers.

OBJECTIVE: To investigate the in vivo intestinal absorption mechanism(s) and systemic availability of fexofenadine in the jejunum, ileum and colon in humans. METHOD: A single dose of fexofenadine hydrochloride (60 mg as solution) was applied under fasting conditions, either alone or directly after a solution of erythromycin lactobionate (corresponding to a dose of 250 mg erythromycin), to the jejunum, ileum and colon in 6 healthy volunteers (3 male and 3 female) using a regional intubation dosing technology (Bioperm AB, Lund, Sweden). A total of 36 fexofenadine administrations were performed. The administration of fexofenadine to the specified location either alone or in combination with erythromycin was conducted in a randomized manner on 2 consecutive days with a 5-day washout period between doses. RESULTS: The plasma AUC for fexofenadine (mean +/- SEM) was higher (2.7-to 2.3-fold, p < 0.001) after application to the jejunum (1090 +/- 134 h x ng/ml) than to the ileum (404 +/- 102 h x ng/ml) or colon (476 +/- 212 h x ng/ml). No significant differences were found between application to the ileum and colon. The administration of erythromycin affected the absorption rate after jejunal application with a prolonged tmax from a median of 40 min (range 10-90 min) to a median of 3 hours (range 10-180 min) (p = 0.009). A change in tmax was not observed with application to the ileum and colon. The concomitant administration of erythromycin in the jejunum tended to increase the plasma AUC of fexofenadine from 1090 +/- 134 to 1750 +/- 305 h x ng/ml (p = 0.069). CONCLUSIONS: The systemic availability of fexofenadine was significantly higher after jejunal administration in accordance with a low permeability compound. The effects of erythromycin suggest that absorption of fexofenadine involves an uptake transport in addition to passive diffusion in the jejunum and predominantly passive diffusion in the ileum and colon.

Effects of hyperbaric oxygen therapy on experimental burn wound healing in rats: a randomized controlled study.

A body of data supports the efficacy of hyperbaric oxygen (HBO2) therapy in the treatment of thermal burns, but the role of HBO2 in the treatment of burn injury remains a subject of controversy. The aim of this study was to evaluate possible positive effects of HBO2 on the experimental burn wound healing. Deep second degree burns were produced on the depilated backs of 70 male Wistar rats using a validated burn protocol. The animals were assigned randomly to one of two groups: 35 to the control group, which was treated with silver sulphadiazine and placebo gas, and 35 to the experimental group, which was treated with silver sulphadiazine and HBO2. The main outcome measure was wound healing, characterized by formation of post-burn edema, neoangiogenesis, number of regeneratory active follicles, necrosis staging, margination of leukocytes, and time of epithelization. A significant reduction of the post-burn edema after treatment with HBO2 (p = 0.009) was found. HBO2 had a beneficial effect on neoangiogenesis (p = 0.009). The number of preserved regeneratory active follicles was significantly higher (p = 0.009) and epithelial regeneration was more rapid in the experimental group (p = 0.048). There were no significant differences for margination of leukocytes (p = 0.55) or necrosis staging (p = 1.00). These data further support earlier conclusions that HBO2 is beneficial in the healing of burn wounds.

Change in strategy of solving psychological tests: evidence of nitrogen narcosis in shallow air-diving.

The depths from 10 to 30 m are usually not considered narcotic in scuba air-diving, and evidence of psychomotor disturbances attributable to nitrogen narcosis at these depths is weak and contradictory. 15 experienced male divers were tested in a chamber at 1, 2, 3, and 4 bars over five consecutive days using a battery of computer generated psychological tests-Computerized Reactionmeter Drenovac (CRD-series). Total test solving time, minimal single task solving time, total "ballast" time, and total number of errors were recorded. Nitrogen narcosis effects were evident at all hyperbaric pressures with marked performance differences among subjects. MANOVA revealed significant effects of nitrogen partial pressure for groups of the same variables as follows: total test solving time (p < 0.001), total "ballast" time (p < 0.001), and total number of errors (p = 0.038), but not for minimal single task solving time. ANOVA showed significant effects of pressure only on tests of visual discrimination of signal location (total test solving time: p = 0.012, total "ballast" time: p < 0.001), simple convergent visual orientation (total test solving time: p = 0.012), and convergent thinking (total test solving time: p = 0.002, total number of errors: p = 0.049). The order of the pressure exposures had no influence on subject performance. Impaired psychomotor processing found during air exposures from 2 to 4 bars suggests that nitrogen narcosis at depths usually considered safe from its effects might be a problem in underwater operations that require accuracy, speed, limited time of performance, and complex psychomotor skills.

Hyperbaric oxygen as a method of therapy of sudden sensorineural hearing loss.

Sudden hearing loss is a sensorineural hearing impairment, which develops over a period of few hours to a few days. Several theories have been proposed regarding the development of sudden sensorineural hearing loss. The incidence of sudden sensorineural hearing loss has been reported to range from 5 to 20 per 100,000 persons per year. Hearing loss is treated with drugs that provide better blood supply to the inner ear and decrease inflammation. The aim of this study is to examine the influence of hyperbaric oxygen therapy in treating sudden sensorineural hearing loss. The beneficial effects of HBO2 on sudden sensorineural hearing loss are probably achieved by an increase in the distribution of O2 dissolved per volume unit of blood circulating trough the regions affected by the lack of oxygen. Sessions were performed on 17 patients, with sudden sensorineural hearing loss that began within 10 days prior to the tests. In the hyperbaric chamber, all patients breathed 100% oxygen at 2.8 bars, for 60 minutes twice a day, either until recovered or for a maximum of 30 sessions. Of the total number of study participants, 12 were male and 5 were female, and their average age was 35.3 years (range: 18 to 68). Before the therapy, an average hearing value was obtained out of five basic frequencies. Hearing was found to be in the range of 61-93 dB in 12 patients, while 5 patients had hearing in the range of 41-60 dB. Following therapy with hyperbaric oxygen, the hearing level of 14 patients was within the range of 0-26 dB, two patients' hearing level increased to 27-40 dB, and one patient's hearing level remained in the range of 41-60 dB. The average hearing level for all patients and for all five basic frequencies was 67.8 dB before therapy, in comparison with 21.6 dB after oxygen therapy (p=0.0003). The average number of sessions in the hyperbaric chamber was 11.9 (range: 5 to 20). The therapy was taken well by all patients. The results of this study, as well as the results of similar studies performed by other authors, indicate for the necessity of performing an additional prospective, random, double-blind study of the effects of hyperbaric oxygen therapy on sudden sensorineural hearing loss, on a large number of patients.

Diving-related fatalities caused by underwater explosions: a report of two cases.

The authors report two cases of diving-related water blast with fatal outcome resulting from nearby underwater explosions. Water blast with fatal outcome almost exclusively occurs in wars at sea. Underwater explosions are extremely rare in diving because of the limited exposure. Forensic findings in both cases reported included expected injuries to gas-filled organs such as the middle ear, lungs, and intestine; some rarely described injuries such as rupture of the liver, spleen, and kidneys; and also some lesions that were not found in a search of the literature: rupture of the heart and contusion of the hypophysis. Injuries caused by fatal underwater explosions should be carefully evaluated in forensic medicine to provide data that may support a criminal investigation.

[Malaria in Croatia: in the past, today and tomorrow]. / Malarija u Hrvatskoj: nekad, danas i sutra.

Until 1964, when officially declared eradicated, malaria had been a major public health problem in Croatia. No autochthonous infections have been noted since 1958. Within ten year period after the eradication three cases were transmitted by transfusion. Until 1998, all other cases, a total of 308, were imported. Within last 10 years 119 cases were noted. The most of infections were caused by P. falciparum (n = 71, 59.66%), than by P. vivax (n = 31, 26.05%), and P. ovale, respectively (n = 1, 0.84%). Mixed infections were noted in 8 cases (6.73%), and the cause remained undetermined in 6 (1.68%). Seamen make the most of those who acquire primary malaria. There are some 30,000 seamen in Croatia. Some 10,000 are on foreign ships, therefore many data are definitely not available or incomplete. An average of 8 Croatian seamen get infected annually, but this number is supposed to be much greater. Mosquitos which are vectors for malaria exist in Croatia even today. Sporadic cases of autochthonous malaria in the neighboring countries, in which malaria was officially eradicated, are a warning that cases of autochthonous malaria might appear in Croatia, too. Due to the increased resistance to known antimalaria drugs including mefloquine, chemoprophylaxis when indicated, campaign against mosquitos, and control of persons who come from the malaria regions are determinants of control of malaria in Croatia, as in accordance with World Health Organization recommendations. Besides, further research of medically interesting insects, including the genus Anopheles, would be useful, at least in the coastal area of Croatia.

[Lyme borreliosis in Croatia from 1987 to 1998--epidemiologic aspects]. / Lajmska borelioza u Hrvatskoj od 1987. do 1998.--epidemioloski aspekt.

Lyme borreliosis is one of the most common diseases originating from natural foci in the Republic of Croatia. Some 200 cases are reported every year to the Epidemiological Department of Croatian National Institute of Public Health, but data from hospital treatment and individual limited research show that the number of infected is certainly higher. Officially reported cases have been used and analysed in this article. Although, aware of the limits of such a source, the results gained with this analysis point to certain epidemiological characteristics of Lyme borreliosis in Croatia, which can be useful. Clinical manifestations might vary, depending on the part of the world, i.e. type of Borrelia involved. In Croatia, skin manifestations are predominant--erythema (chronicum) migrans. The disease generally does not occur in Southern Croatia; it has been only sporadically reported in the area south of Zadar. Although the tick, the vector of this disease, can be found everywhere in Croatia, data about vector species and their presence in the coastal area are not complete or they are missing. Therefore, additional entomological, epidemiological, and clinical research are necessary to clarify the absence of Lyme borreliosis in Southern Croatia.

Recreational diving--an overview of selected medical aspects.

Recreational diving has become very popular in Croatia. Selected medical aspects of it are reviewed in this article.

Hyperbaric oxygenation as adjuvant therapy to surgery of emphysematous cholecystitis.

Three cases of emphysematous cholecystitis are presented. The role of hyperbaric oxygenation as excellent adjuvant therapy to urgent surgical as well as intensive conservative treatment is emphasized.

Effect of maternal hyperoxygenation on experimentally produced uteroplacental insufficiency in the rat.

The paper examines the effects of maternal hyperoxygenation on uteroplacental insufficiency produced by ligation of the uterine artery. Maternal hyperoxygenation did not significantly affect experimentally produced growth retardation or survival of the fetuses from the ligated horn. Analysis of the vascular anatomy revealed that additional oxygen improves the survival of fetuses compromised by uteroplacental insufficiency only in the presence of anastomosis between the uterine and ovarian arteries. The study demonstrated the importance of that anastomosis in evaluating the results obtained by this experimental model.

Predictive value of Müller maneuver, cephalometry and clinical features for the outcome of uvulopalatopharyngoplasty. Evaluation of predictive factors using discriminant analysis in 30 sleep apnea patients.

The success rate of uvulopalatopharyngoplasty (UPPP) in the treatment of obstructive sleep apnea is generally only 50-60%. In order to improve this, various predictive factors for the outcome of UPPP were studied, including the Müller maneuver and cephalometry. Thirty unselected consecutive patients with obstructive sleep apnea (median apnea index (AI) 26 apneas/h, range 5-78) underwent UPPP with standard tonsillectomy except in the case of small tonsils and using CO2 laser for the palatal resection. Polysomnographic control 5 months after surgery showed that 63% of all patients had obtained a reduction in AI > or = 50% including an AI < 20 after surgery. Tonsillectomy had no influence on the outcome. Further, the Müller maneuver did not predict the outcome, whereas cephalometry proved to be of good predictive value. Lowered position of the hyoid bone, increased cranio-cervical angle and shortening of the maxilla length were significantly associated with poor results of UPPP, as were overweight, narrowing of the hypopharynx, the severity of sleep apnea, and hypersomnia. However, in a discriminant analysis containing all these variables, the three cephalometric measurements together with hypersomnia were most closely associated with the outcome of UPPP. A predictive model containing these four variables could correctly classify 83% of the patients in the present study. The model had a false positive rate of 7% in predicting a successful outcome. This indicates that cephalometry is mandatory in the selection of UPPP candidates and that a predictive model containing some or all of the four variables may substantially improve the success rate.

[Pulse oximetry and obstructive sleep apnea]. / Pulsoximetri og obstruktiv søvnapnø.

We report a case of a 54 years old man, treated with Methylphenidate (Ritalin) because of narcolepsy, who was referred with suspected vertebro-basilar insufficiency. In the hospital, apnoea during sleep attacks were observed. A polysomnography showed marked obstructive sleep apnoea with a disturbed hypnogram, but during the apnoeas the oxygen saturation only decreased by three to six percent. If a patient suspected for obstructive sleep apnoea has only small desaturations, an oximetry can be insensitive as the only "sleep examination", and a full polysomnography is recommended.

Hyperbaric oxygen dose of choice in the treatment of glaucoma.

The subjects in the study were 111 patients with open angle glaucoma who were submitted to treatment by hyperbaric oxygenation. Two groups were formed at random, an experimental one of 91 patients and a control group of 20 patients. The experimental group consisted of four subgroups classified according to the course of treatment they received: 30 sessions (31 patients), 20 sessions (20 patients), 15 sessions (20 patients) and 10 sessions (20 patients). For the treatment a large walk-in recompression chamber was utilized, once a day, at a pressure of 2.0 bars, for 90 minutes. Visual acuity and mean intraocular pressure values taken before and after hyperbaric oxygen treatment did not show a statistically significant difference either between the treated and control subjects, or at control examinations after three and six months. During the follow-up period, changes in the visual field area in control subjects were discrete and statistically not significant. At the same time the visual field values increased after the therapy in all the subgroups. In the 10-session course subgroup the increase was not statistically significant. In all other subgroups, statistical significance was at the level of P < 0.01. Control after three months demonstrated the same level of statistical significance; control at the end of six months failed to show a statistically significant difference. The 20-session course is recommended for initial treatment. When visual field values return to 50 percent of the improved values achieved during initial treatment, it is suggested that hyperbaric oxygen treatment be repeated.

[A stink bomb in an office environment. Sick building syndrome with toxic rhinitis after exposure to fusel]. / En stinkbombe i kontorlandskabet. Sick building syndrome med toksisk rhinitis efter eksponering for fusel.

In 1983 WHO, defined "The Sick Building Syndrome". Various conditions influence the indoor climate, among others the degassing of chemicals. An epidemic of sick building syndrome is described in a two year old office building. The symptoms appeared after exposure to toxic chemicals released by a stink bomb--a form of exposure not previously described in the literature. Gas chromatographic analysis of the content of the stink bomb revealed 22 different chemicals likely to be remains from an alcoholic fermentation process. Twenty-four employees were exposed. A questionnaire investigation of the employees revealed that seven had symptoms related to the exposure. A clinical investigation of those who claimed to have symptoms took place. Six of the seven patients were investigated. They all had toxic rhinitis with bleeding. Owing to an unsystematic procedure it took more than two months before the indoor climate was normalized. The toxic rhinitis and other symptoms gradually decreased over more than four months. In order to minimize potential health damage due to the sick building syndrome, we recommend that experts should be consulted within this particular field.