Long-term application of adrenergic agonists modulates nociceptive ion channels.

Dorsal root ganglia (DRG) neurons transduce and convey somatosensory information from the periphery to the central nervous system. Adrenergic mediators are known to modulate nociceptive inputs in DRG neurons, acting as up- or down-regulators of neuronal excitability. They are also important in the development of sympathetic neuropathy. ATP-activated P2X channels and capsaicin-activated TRPV1 channels are directly involved in the transduction of nociceptive stimuli. In this work, we show that long-term (up to 3 days) in vitro stimulation of DRG neurons with selective α1-adrenergic agonist increased slow but not fast ATP-activated currents, with no effect on capsaicin currents. Selective agonists for α2, ß1 and ß3-adrenergic receptors decreased capsaicin activated currents and had no effect on ATP currents. Capsaicin currents were associated with increased neuronal excitability, while none of the adrenergic modulators produced change in rheobase. These results demonstrate that chronic adrenergic activation modulates two nociceptive transducer molecules, increasing or decreasing channel current depending on the adrenergic receptor subtype. These observations aid our understanding of nociceptive or antinociceptive effects of adrenergic agonists.

Risk factors and survival in patients with COVID-19 in northeastern Brazil.

BACKGROUND: Knowledge about the epidemiology and risk factors surrounding COVID-19 contributes to developing better health strategies to combat the disease. OBJECTIVE: This study aimed to establish a survival analysis and identify the risk factors for patients with COVID-19 in an upper middle-income city in Brazil. METHODS: A retrospective cohort study was conducted with 280 hospitalized patients with COVID-19. The eCOVID platform provided data to monitor COVID-19 cases and help the communication between professionals. RESULTS: Age ≥ 65 years was associated with decreased survival (54.8%), and females had a lower survival rate than males (p = 0.01). Regarding risk factors, urea concentration (p<0.001), hospital length of stay (p = 0.002), oxygen concentration (p = 0.005), and age (p = 0.02) were associated with death. CONCLUSION: Age, hospital length of stay, high blood urea concentration, and low oxygen concentration were associated with death by COVID-19 in the studied population. These findings corroborate with studies conducted in research centers worldwide.

Epidemiology of Clinical Sporotrichosis in the Americas in the Last Ten Years.

BACKGROUND: Sporotrichosis is a fungal infection caused by species of the Sporothrix genus. Presently, the prevalence of sporotrichosis in the Americas is unknown, so this study aims to analyze the cases reported in the past 10 years. METHODS: An advanced search was conducted from 2012 to 2022 in English and Spanish in PUBMED, SciELO, and Cochrane, with the terms: "sporotrichosis", "lymphocutaneous sporotrichosis", "fixed sporotrichosis", "mycosis", "Sporothrix spp.", "Sporothrix complex", "S. schenckii sensu stricto", "S. schenckii sensu lato", "S. globose", "S. brasiliensis", "S. luriei". Sporotrichosis is a fungal infection caused by species of the Sporothrix genus associated with "pathogenicity" or "epidemiology". RESULTS: A total of 124 articles were found in the Americas, corresponding to 12,568 patients. Of these, 87.38% of cases were reported in South America, 11.62% in North America, and 1.00% in Central America and the Caribbean. Brazil, Peru, and Mexico had the highest number of cases. The most prevalent etiological agents were S. schenckii complex/Sporothrix spp. (52.91%), S. schenckii (42.38%), others (4.68%), and Not Determined (ND) (0.03%). The most frequent form of the disease was lymphocutaneous infection; however, the infection type was not determined in 5639 cases. Among the diagnostic methods, culture was the most used. CONCLUSIONS: There is a high occurrence of cases reported in the literature. South America is the region with the highest number of reports because of its environment (climate, inhalation of spores, etc.), zoonotic transmission (scratches and sneezes from contaminated animals), and possible traumatic inoculation due to outdoor activities (agriculture, gardening, and related occupations). Molecular diagnosis has not been sufficiently developed due to its high cost.

New Applications of Photodynamic Therapy in the Management of Candidiasis.

The most important aetiological agent of opportunistic mycoses worldwide is Candida spp. These yeasts can cause severe infections in the host, which may be fatal. Isolates of Candida albicans occur with greater frequency and variable resistance patterns. Photodynamic therapy (PDT) has been recognised as an alternative treatment to kill pathogenic microorganisms. PDT utilises a photosensitizer, which is activated at a specific wavelength and oxygen concentration. Their reaction yields reactive oxygen species that kill the infectious microorganism. A systematic review of new applications of PDT in the management of candidiasis was performed. Of the 222 studies selected for in-depth screening, 84 were included in this study. All the studies reported the antifungal effectiveness, toxicity and dosimetry of treatment with antimicrobial PDT (aPDT) with different photosensitizers against Candida spp. The manuscripts that are discussed reveal the breadth of the new applications of aPDT against Candida spp., which are resistant to common antifungals. aPDT has superior performance compared to conventional antifungal therapies. With further studies, aPDT should prove valuable in daily clinical practice.

An overview of the treatment of cutaneous leishmaniasis.

Leishmaniasis is a neglected tropical disease caused by species of Leishmania, with a broad spectrum of clinical manifestations, such as cutaneous, visceral, and mucocutaneous presentations. Many drugs are used for its treatment, and a current effective one is a pentavalent antimonial, especially in developing countries. In this review, we discuss recent proposed therapies as well as their side effects.

Bioactive molecule optimized for biofilm reduction related to childhood caries.

Aim: To evaluate antimicrobial activity of a new nitrochalcone (NC-E08) against Candida albicans and Streptococcus mutans, and its toxicity. Materials & methods: Minimum inhibitory concentration (MIC) and minimum bactericidal concentration/minimum fungicidal concentration (MFC) were determined against C. albicans and S. mutans, as well as antibiofilm potential and toxicity (human gingival fibroblast and Galleria mellonella). Infection and treatment were performed in G. mellonella. Results & conclusion: NC-E08 showed antimicrobial activity in C. albicans (MIC: 0.054 mM) and S. mutans (MIC: 0.013 mM); 10xMIC treatment reduced 4.0 log10 biofilms for both strains and there was a reduction in survival of mixed biofilms of C. albicans and S. mutans (6.0 and 4.0 log10, respectively). NC-E08 showed no cytotoxicity in human gingival fibroblast cells and G. mellonella. NC-E08 after larval infection protected them 90% (p < 0.05). Thus, is a promising one for the prevention and treatment of S. mutans and C. albicans infections.

Circulating catecholamines are associated with biobehavioral factors and anxiety symptoms in head and neck cancer patients.

Studies have shown that stress-related catecholamines may affect cancer progression. However, little is known about catecholamine secretion profiles in head and neck cancer patients. The present study investigated plasma norepinephrine and epinephrine levels in head and neck squamous cell carcinoma (HNSCC) patients and patients with oral leukoplakia, as well as their association with clinicopathological and biobehavioral variables and anxiety symptoms. A total of 93 patients with HNSCC and 32 patients with oral leukoplakia were included. Plasma norepinephrine and epinephrine levels were measured by high performance liquid chromatography with electrochemical detection (HPLC-ED), and psychological anxiety levels were measured by the Beck Anxiety Inventory (BAI). Plasma norepinephrine and epinephrine concentrations were significantly higher in patients with oral and oropharyngeal squamous cell carcinoma (SCC) compared to non-cancer patients. Oral SCC patients displayed plasma norepinephrine levels about six times higher than oropharyngeal SCC patients, and nine times higher than oral leukoplakia patients (p < .001). Plasma epinephrine levels in oral SCC patients were higher compared to the oropharyngeal SCC (p = .0097) and leukoplakia (p < .0001) patients. Oropharyngeal SCC patients had higher plasma norepinephrine (p = .0382) and epinephrine levels (p = .045) than patients with oral leukoplakia. Multiple regression analyses showed that a history of high alcohol consumption was predictive for reduced plasma norepinephrine levels in the oral SCC group (p < .001). Anxiety symptom of "hand tremor" measured by the BAI was an independent predictor for higher plasma norepinephrine levels in HNSCC patients (ß = 157.5, p = .0377), while the "heart pounding/racing" symptom was independently associated with higher plasma epinephrine levels in the oropharyngeal SCC group (ß = 15.8, p = .0441). In oral leukoplakia patients, sleep deprivation and worse sleep quality were independent predictors for higher plasma norepinephrine levels, while severe tobacco consumption and higher anxiety levels were factors for higher plasma epinephrine levels. These findings suggest that head and neck cancer patients display sympathetic nervous system hyperactivity, and that changes in circulating catecholamines may be associated with alcohol consumption, as well as withdrawal-related anxiety symptoms.

Characterization of resolution, sensitivity, and shielding of a gamma-probe for sentinel lymph node localization: an experimental study.

OBJECTIVE: The aim of this study was to evaluate angular, spatial, and energy resolution, sensitivity, and shielding of a gamma-probe. MATERIALS AND METHODS: The EUROPROBE II gamma-probe (EuroRad) with sources of technetium-99m was assessed according to NEMA NU-3-2004. Resolution tests were evaluated considering the full width at half maximum (FWHM). The following parameters were evaluated: angular resolution in air, spatial resolution with a scattering medium and in air, energy resolution, and sensitivity and shielding. The collimator was used to evaluate angular and spatial resolution, sensitivity, and shielding. Background radiation was considered and did not affect the counts. RESULTS: FWHM of angular resolution (at 3/30 cm) was 39.17°/33.13° with the collimator and 74.08°/71.51° without the collimator; FWHM of spatial resolution in air at 10 mm was 13.32 mm with the collimator and 21.23 mm without the collimator. Energy resolution (%FWHM) was 20.51%. Sensitivity at 10 mm was 4.642±5 cps/MBq without the collimator and 1.063±2 cps/MBq with the collimator; shielding effectiveness of the probe tip was 99.52%. Background was not relevant to the counts. CONCLUSION: We showed that the collimator improved angular and spatial resolution to the detriment of sensitivity. Feasible results of energy resolution, sensitivity, and shielding were achieved.

Lollipop-induced oral lichenoid reaction in a child.

BACKGROUND: Oral lichenoid reactions (OLRs) have been rarely reported in pediatric patients. CASE REPORT: This article reports an unusual case of a 15-year-old girl who had white plaques in tongue and buccal mucosa oral which initially were diagnosed as oral lichen planus (OLP). At first, the patient and her family denied systemic or local medication use. Biopsy was performed, and histopathological aspects were suggestive of OLP. Despite the attempt of treatment with topical corticoid, the lesions did not recede. Patient's behavior and medical history were again investigated and revealed that she had been using almost daily in her school an artificially colored and flavored lollipop. One week after removing lollipop use behavior, the oral lesions showed complete resolution and OLR diagnosis was defined. CONCLUSION: The present case denotes that OLR should be considered in the differential diagnosis of oral white plates in children and artificially colored sweets can be its causal agent.

Evaluation of oesophageal transit velocity using the improved Demons technique.

PURPOSE: This paper presents a novel method to compute oesophageal transit velocity in a direct and automatized manner by the registration of scintigraphy images. METHODS: A total of 36 images from nine healthy volunteers were processed. Four dynamic image series per volunteer were acquired after a minimum 8 h fast. Each acquisition was made following the ingestion of 5 ml saline labelled with about 26 MBq (700 µCi) technetium-99m phytate in a single swallow. Between the acquisitions, another two swallows of 5 ml saline were performed to clear the oesophagus. The composite acquired files were made of 240 frames of anterior and posterior views. Each frame is the accumulate count for 250 ms.At the end of acquisitions, the images were corrected for radioactive decay, the geometric mean was computed between the anterior and posterior views and the registration of a set of subsequent images was performed. Utilizing the improved Demons technique, we obtained from the deformation field the regional resultant velocity, which is directly related to the oesophagus transit velocity. RESULTS: The mean regional resulting velocities decreases progressively from the proximal to the distal oesophageal portions and, at the proximal portion, is virtually identical to the primary peristaltic pump typical velocity. Comparison between this parameter and 'time-activity' curves reveals consistency in velocities obtained using both methods, for the proximal portion. CONCLUSION: Application of the improved Demons technique, as an easy and automated method to evaluate velocities of oesophageal bolus transit, is feasible and seems to yield consistent data, particularly for the proximal oesophagus.

Segmented independent component analysis for improved separation of fetal cardiac signals from nonstationary fetal magnetocardiograms.

Fetal magnetocardiograms (fMCGs) have been successfully processed with independent component analysis (ICA) to separate the fetal cardiac signals, but ICA effectiveness can be limited by signal nonstationarities due to fetal movements. We propose an ICA-based method to improve the quality of fetal signals separated from fMCG affected by fetal movements. This technique (SegICA) includes a procedure to detect signal nonstationarities, according to which the fMCG recordings are divided in stationary segments that are then processed with ICA. The first and second statistical moments and the signal polarity reversal were used at different threshold levels to detect signal transients. SegICA effectiveness was assessed in two fMCG datasets (with and without fetal movements) by comparing the signal-to-noise ratio (SNR) of the signals extracted with ICA and with SegICA. Results showed that the SNR of fetal signals affected by fetal movements improved with SegICA, whereas the SNR gain was negligible elsewhere. The best measure to detect signal nonstationarities of physiological origin was signal polarity reversal at threshold level 0.9. The first statistical moment also provided good results at threshold level 0.6. SegICA seems a promising method to separate fetal cardiac signals of improved quality from nonstationary fMCG recordings affected by fetal movements.

Towards component-based validation of GATE: aspects of the coincidence processor.

GATE is public domain software widely used for Monte Carlo simulation in emission tomography. Validations of GATE have primarily been performed on a whole-system basis, leaving the possibility that errors in one sub-system may be offset by errors in others. We assess the accuracy of the GATE PET coincidence generation sub-system in isolation, focusing on the options most closely modeling the majority of commercially available scanners. Independent coincidence generators were coded by teams at Toshiba Medical Research Unit (TMRU) and UC Davis. A model similar to the Siemens mCT scanner was created in GATE. Annihilation photons interacting with the detectors were recorded. Coincidences were generated using GATE, TMRU and UC Davis code and results compared to "ground truth" obtained from the history of the photon interactions. GATE was tested twice, once with every qualified single event opening a time window and initiating a coincidence check (the "multiple window method"), and once where a time window is opened and a coincidence check initiated only by the first single event to occur after the end of the prior time window (the "single window method"). True, scattered and random coincidences were compared. Noise equivalent count rates were also computed and compared. The TMRU and UC Davis coincidence generators agree well with ground truth. With GATE, reasonable accuracy can be obtained if the single window method option is chosen and random coincidences are estimated without use of the delayed coincidence option. However in this GATE version, other parameter combinations can result in significant errors.

A novel dynamic scintigraphic technique for assessing duodenal contractions during gastric emptying in humans: a feasibility study.

Duodenal contractions are thought to play a role in the control of gastric emptying. Although noninvasive techniques, such as ultrasonography and MRI, have been proposed for studying duodenal contractile activity in humans, there are no reports on the use of scintigraphy for this purpose. This work aimed to describe a novel scintigraphic technique for assessing duodenal contractility during gastric emptying in humans, and to present preliminary data on the frequency and amplitude of contractions detected in three different duodenal segments. Fasted young healthy volunteers (N=12) were given either a liquid or a solid test meal of similar calorie content (400 kcal) labeled with 99mTc-phytate. Static images were collected to determine gastric emptying. Dynamic images of the anterior aspect of the abdomen (1 frame/s) were also acquired periodically in a standard position for 256 s at 15-30 min intervals. 'Activity versus time' curves were generated for regions of interest corresponding to the proximal, middle, and distal duodenal segments. Curves were digitally filtered and processed to estimate both dominant frequency (fast Fourier transform) and amplitude (mean ejection fraction) of postprandial duodenal contractions. There were no significant differences regarding dominant frequency among proximal, middle, and distal duodenal regions of interest. In addition, there were no significant differences between the liquid and the solid meal in terms of either frequency or amplitude of duodenal contractions. Characterization of duodenal contractions in humans using scintigraphy is feasible and yields consistent data for both the frequency and the amplitude of postprandial contractions, which seems to be rather independent of meal consistency.

The challenges posed by climate change to successful ageing.

Ever since the 2003 heat wave that caused 70,000 heat deaths, the dramatic consequences of climate change and rising temperatures in Europe have become an intensively researched topic. During heat waves, the older urban adult population is at highest risk. The STOPHOT project is the first investigation in Austria to establish a comprehensive knowledge base on heat perception, awareness of heat risks and adaptive/coping behaviours among older adults. The main research questions include: (1) Does climate change endanger the chances of successful ageing in urban areas? (2) How do age, social inequalities and the living environment intersect with environmental stressors in affecting successful ageing? (3) Which heat adaption strategies do older adults deploy and to what extent can they mediate heat stress in an effort to increase chances of successful ageing under the conditions of climate change? The results indicate that climate change and rising temperatures are in fact one important determinant of whether and how an older person can maintain well-being in later life. Older adults (> 65 years) with a low socio-economic status and poor health conditions, who tend to be socially isolated, are most at risk. However, no 'heat island effect' of the residential environment could be found. How much a person suffers from heat stress is highly dependent on the adaption strategies deployed. Adaption strategies of older urban residents mostly centred on body-related measures, such as drinking more or wearing lighter clothes, and indoor-centred measures, particularly avoiding the outdoors.

[Organ and kidney function preservation in renal cell carcinoma]. / Organ- und Funktionserhalt beim Nierenzellkarzinom.

BACKGROUND: The organ-preserving partial nephrectomy has increasingly established itself in small unilateral renal tumours (<4 cm) with contralateral healthy kidney and counter gained in recent years in importance. There was found a significantly increased cardiovascular mortality rate and deteriorated quality of life, the more intact kidney tissue has been removed. OBJECTIVES: In the present study, the influence of pre- and perioperative factors on direct postoperative course was examined, including 5-year survival rate and relapse behaviour after open organ-preserving partial nephrectomy in our own collective. MATERIALS AND METHODS: In this retrospective study of 1657 patients were collected, who underwent surgery between 2007 and 2013 in the Department of Urology at the University Hospital Essen because of a renal tumour. 38 % of these operations (n = 636) were performed organ-preserving. In this trial there are factors identified that have an impact on need of blood transfusion and length of hospitalization in organ-preserving operation method. RESULTS: No independent parameter can be determined for the need of blood transfusion. Tumour size and thus time of resection procedure does not affect the need of erythrocytes administration. In addition, the tumour size influences neither the postoperative serum-haemoglobin nor serum-creatinine. Increased patient age and female gender are identified as non-modifiable factors, which cause a longer hospitalisation. Postoperative pain therapy can be considered as a variable size, which does not affect the length of hospital stay. Modifiable factors that increase the overall length of stay, however, are the type of direct postoperative monitoring (ICU vs. anaesthetic recovery room) and the administration of blood transfusions. CONCLUSIONS: There are constant factors, which can be associated with a longer residence time in the framework of an organ-preserving partial nephrectomy. Further there is shown evidence of the independence of the tumour size - in addition to proven good oncological results - of an extension of indication of organ-preserving nephrectomy of tumours > 4 cm.

Dietary phytosterol does not accumulate in the arterial wall and prevents atherosclerosis of LDLr-KO mice.

SCOPE: There have been conflicting reports on the usefulness of phytosterols (PS) in preventing atherosclerosis. We evaluated the effects of dietary PS supplementation in LDLr-KO male mice on the plasma and aorta sterol concentrations and on atherosclerotic lesion development. METHODS AND RESULTS: Mice were fed a high fat diet (40% of energy) supplemented with or without PS (2% w/w, n = 10). Plasma and arterial wall cholesterol and PS concentrations, lesion area, macrophage infiltration, and mRNA expression from LOX-1, CD36, ABCA1 and ABCG1 in peritoneal macrophages were measured. After 16 weeks, the plasma cholesterol concentration in PS mice was lower than that in the controls (p = 0.02) and in the arterial wall (p = 0.03). Plasma PS concentrations were higher in PS-fed animals than in controls (p < 0.0001); however, the arterial wall PS concentration did not differ between groups. The atherosclerotic lesion area in the PS group (n = 5) was smaller than that in controls (p = 0.0062) and the macrophage area (p = 0.0007). PS correlates negatively with arterial lipid content and macrophage (r = -0.76; p < 0.05). PS supplementation induced lower ABCG1 mRNA expression (p < 0.05). CONCLUSIONS: Despite inducing an increase in PS plasma concentration, PS supplementation is not associated with its accumulation in the arterial wall and prevents atherosclerotic lesion development.

Verbal and visual stimulation effects on rectus femoris and biceps femoris muscles during isometric and concentric.

BACKGROUND: Coactivation may be both desirable (injury prevention) or undesirable (strength measurement). In this context, different styles of muscle strength stimulus have being investigated. In this study we evaluated the effects of verbal and visual stimulation on rectus femoris and biceps femoris muscles contraction during isometric and concentric. METHODS: We investigated 13 men (age =23.1 ± 3.8 years old; body mass =75.6 ± 9.1 kg; height =1.8 ± 0.07 m). We used the isokinetic dynamometer BIODEX device and an electromyographic (EMG) system. We evaluated the maximum isometric and isokinetic knee extension and flexion at 60°/s. The following conditions were evaluated: without visual nor verbal command (control); verbal command; visual command and; verbal and visual command. In relation to the concentric contraction, the volunteers performed five reciprocal and continuous contractions at 60°/s. With respect to isometric contractions it was made three contractions of five seconds for flexion and extension in a period of one minute. RESULTS: We found that the peak torque during isometric flexion was higher in the subjects in the VVC condition (p > 0.05). In relation to muscle coactivation, the subjects presented higher values at the control condition (p > 0.05). CONCLUSION: We suggest that this type of stimulus is effective for the lower limbs.