Oral colonization by gram-negative bacilli in patients with hematologic malignancies and solid tumors compared with healthy controls.

BACKGROUND: Colonization of the oropharynx with gram-negative bacilli (GNB) is considered a negative prognostic factor in immunocompromised individuals. Hemato-oncologic patients represent a high-risk group due to their immunodeficiencies and associated treatments. This study aimed to determine the rates of oral colonization by GNB, associated factors, and clinical outcomes in patients with hematologic malignancies and solid tumors compared with healthy subjects. METHODS: We conducted a comparative study of hemato-oncologic patients and healthy subjects from August to October 2022. Swabs were taken from the oral cavity; specimens with GNB were identified and tested for antimicrobial susceptibility. RESULTS: We included 206 participants (103 hemato-oncologic patients and 103 healthy subjects). Hemato-oncologic patients had higher rates of oral colonization by GNB (34% vs. 17%, P = 0.007) and GNB resistant to third-generation cephalosporins (11.6% vs. 0%, P < 0.001) compared to healthy subjects. Klebsiella spp. was the predominant genus in both groups. The factor associated with oral colonization by GNB was a Charlson index ≥ 3, while ≥ 3 dental visits per year were a protective factor. Regarding colonization by resistant GNB in oncology patients, antibiotic therapy and a Charlson index ≥ 5 were identified as associated factors, while better physical functionality (ECOG ≤ 2) was associated with less colonization. Hemato-oncologic patients colonized with GNB had more 30-day infectious complications (30.5% vs. 2.9%, P = 0.0001) than non-colonized patients. CONCLUSION: Oral colonization by GNB and resistant GNB are prevalent in cancer patients, especially those with higher scores on the severity scales. Infectious complications occurred more frequently in colonized patients. There is a knowledge gap about dental hygiene practices in hemato-oncologic patients colonized by GNB. Our results suggest that patients' hygienic-dietary habits, especially frequent dental visits, are a protective factor against colonization.

Statistical and agent-based modelling of the transmissibility of different SARS-CoV-2 variants in England and impact of different interventions.

The English SARS-CoV-2 epidemic has been affected by the emergence of new viral variants such as B.1.177, Alpha and Delta, and changing restrictions. We used statistical models and the agent-based model Covasim, in June 2021, to estimate B.1.177 to be 20% more transmissible than the wild type, Alpha to be 50-80% more transmissible than B.1.177 and Delta to be 65-90% more transmissible than Alpha. Using these estimates in Covasim (calibrated 1 September 2020 to 20 June 2021), in June 2021, we found that due to the high transmissibility of Delta, resurgence in infections driven by the Delta variant would not be prevented, but would be strongly reduced by delaying the relaxation of restrictions by one month and with continued vaccination. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.

Collagen content in the bladder of men with LUTS undergoing open prostatectomy: A pilot study.

AIMS: To evaluate the collagen content in the bladder wall of men undergoing open prostate surgery. METHODS: From July 2014 to August 2016, men aged ≥ 50 years, presenting LUTS and undergoing open prostate surgery due to benign prostatic enlargement (BPE) or prostate cancer were prospectively enrolled. Preoperative assessment included validated questionnaires (IPSS and OAB-V8), lower urinary tract ultrasound, and urodynamics. Bladder biopsies were obtained during open prostatectomy for determination of collagen content (sirius red-picric acid stain; polarized light analysis). Collagen to smooth muscle ratio (C/M) in the detrusor was measured and its relationship with preoperative parameters was investigated. The level of significance was P < 0.05. RESULTS: Thirty-eight consecutive patients were included in this pilot study. Mean age was 66.36 ± 6.44 years and mean IPSS was 11.05 ± 8.72 points. Men diagnosed with diabetes mellitus (DM2) were found to have higher collagen content in the bladder wall when compared to non-diabetic patients (17.71 ± 6.82% vs 12.46 ± 5.2%, respectively; P = 0.024). Reduced bladder compliance was also marker for higher collagen content (P = 0.042). Bladder outlet obstruction (BOO) was not a predictor of increased collagen deposition in the bladder wall (P = 0.75). Patients with PVR ≥ 200 mL showed a higher collagen to smooth muscle ratio in the bladder wall (P = 0.036). CONCLUSIONS: DM2 and urodynamic parameters, such as increased PVR and reduced bladder compliance, were associated with higher collagen content in the bladder wall of men with LUTS.

Ecological succession of the microbial communities of an air-conditioning cooling coil in the tropics.

Air-conditioning systems harbor microorganisms, potentially spreading them to indoor environments. While air and surfaces in air-conditioning systems are periodically sampled as potential sources of indoor microbes, little is known about the dynamics of cooling coil-associated communities and their effect on the downstream airflow. Here, we conducted a 4-week time series sampling to characterize the succession of an air-conditioning duct and cooling coil after cleaning. Using an universal primer pair targeting hypervariable regions of the 16S/18S ribosomal RNA, we observed a community succession for the condensed water, with the most abundant airborne taxon Agaricomycetes fungi dominating the initial phase and Sphingomonas bacteria becoming the most prevalent taxa toward the end of the experiment. Duplicate air samples collected upstream and downstream of the coil suggest that the system does not act as ecological filter or source/sink for specific microbial taxa during the duration of the experiment.

Olea Europea-derived phenolic products attenuate antinociceptive morphine tolerance: an innovative strategic approach to treat cancer pain.

Morphine and related opioid drugs are currently the major drugs for severe pain. Their clinical utility is limited in the management of severe cancer pain due to the rapid development of tolerance. Restoring opioid efficacy is therefore of great clinical importance. A great body of evidence suggests the key role of free radicals and posttranslational modulation in the development of tolerance to the analgesic activity of morphine. Epidemiological studies have shown a relationship between the Mediterranean diet and a reduced incidence of pathologies such as coronary heart disease and cancer. A central hallmark of this diet is the high consumption of virgin olive oil as the main source of fat which contains antioxidant components in the non-saponifiable fraction, including phenolic compounds absent in seed oils. Here, we show that in a rodent model of opiate tolerance, removal of the free radicals with phenolic compounds of olive oil such as hydroxytyrosol and oleuropein reinstates the analgesic action of morphine. Chronic injection of morphine in mice led to the development of tolerance and this was associated with increased nitrotyrosin and malondialdehyde (MDA) formation together with nitration and deactivation of MnSOD in the spinal cord. Removal of free radicals by hydroxytyrosol and oleuropein blocked morphine tolerance by inhibiting nitration and MDA formation and replacing the MnSOD activity. The phenolic fraction of virgin olive oil exerts antioxidant activities in vivo and free radicals generation occurring during chronic morphine administration play a crucial role in the development of opioid tolerance. Our data suggest novel therapeutic approach in the management of chronic cancer pain, in particular for those patients who require long-term opioid treatment for pain relief without development of tolerance.

Effect of MN (III) tetrakis (4-benzoic acid) porphyrin by photodynamically generated free radicals on SODs keratinocytes.

Superoxide, a reactive form of oxygen, can be produced in vivo either in normal and under pathophysiologic conditions or by photosensitizing chemicals, as during photodynamic treatment. Photodynamic therapies (PDT), widely adopted in Dermatology and Oncology, are known to generate reactive oxygen species (ROS) and may contribute to structural alterations and oxidatively generated modifications of cellular antioxidants. We hypothesized that over-production of free radicals would decrease the enzymatic activities of endogenous cellular antioxidants. To test this hypothesis, keratinocytes were treated with the photosensitizer Photofrin plus visible light to produce free radicals and CuZnSOD and MnSOD activities were measured. Photodynamic treatment of keratinocytes increases malonylaldehyde production, nitrotyrosine staining and superoxide production. The enzymatic activities of CuZnSOD and MnSOD were significantly decreased after Photofrin plus visible light treatment. Our results suggest that the main cellular antioxidant system can be inactivated by photodynamically generated ROS. Pretreatment of keratinocytes with free radicals scavenger such as Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) was able to restore the endogenous antioxidant system activities, inhibiting the MDA formation, nitrotyrosine staining and superoxide formation. Antioxidant therapy could therefore be a useful tool in protecting healthy epidermal cells against common side effects induced by antitumor targeted therapies.

Probabilistic predictions of SIS epidemics on networks based on population-level observations.

We predict the future course of ongoing susceptible-infected-susceptible (SIS) epidemics on regular, Erdos-Rényi and Barabási-Albert networks. It is known that the contact network influences the spread of an epidemic within a population. Therefore, observations of an epidemic, in this case at the population-level, contain information about the underlying network. This information, in turn, is useful for predicting the future course of an ongoing epidemic. To exploit this in a prediction framework, the exact high-dimensional stochastic model of an SIS epidemic on a network is approximated by a lower-dimensional surrogate model. The surrogate model is based on a birth-and-death process; the effect of the underlying network is described by a parametric model for the birth rates. We demonstrate empirically that the surrogate model captures the intrinsic stochasticity of the epidemic once it reaches a point from which it will not die out. Bayesian parameter inference allows for uncertainty about the model parameters and the class of the underlying network to be incorporated directly into probabilistic predictions. An evaluation of a number of scenarios shows that in most cases the resulting prediction intervals adequately quantify the prediction uncertainty. As long as the population-level data is available over a long-enough period, even if not sampled frequently, the model leads to excellent predictions where the underlying network is correctly identified and prediction uncertainty mainly reflects the intrinsic stochasticity of the spreading epidemic. For predictions inferred from shorter observational periods, uncertainty about parameters and network class dominate prediction uncertainty. The proposed method relies on minimal data at population-level, which is always likely to be available. This, combined with its numerical efficiency, makes the proposed method attractive to be used either as a standalone inference and prediction scheme or in conjunction with other inference and/or predictive models.

Terahertz imaging demonstrates its diagnostic potential and reveals a relationship between cutaneous dehydration and neuropathy for diabetic foot syndrome patients.

Diabetic foot syndrome, a long term consequence of Diabetes Mellitus, is the most common cause of non-traumatic amputations. Around 8% of the world population suffers from diabetes, 15% of diabetic patients present a diabetic foot ulcer which leads to amputation in 2.5% of the cases. There is no objective method for the early diagnosis and prevention of the syndrome and its consequences. We test terahertz imaging, which is capable of mapping the cutaneous hydration, for the evaluation of the diabetic foot deterioration as an early diagnostic test as well as ulcers prevention and tracking tool. Furthermore, the analysis of our terahertz measurements combined with neurological and vascular assessment of the patients indicates that the dehydration is mainly related to the peripheral neuropathy without a significant vascular cause.

Temperature-dependent global gene expression in the Antarctic archaeon Methanococcoides burtonii.

Methanococcoides burtonii is a member of the Archaea that was isolated from Ace Lake in Antarctica and is a valuable model for studying cold adaptation. Low temperature transcriptional regulation of global gene expression, and the arrangement of transcriptional units in cold-adapted archaea has not been studied. We developed a microarray for determining which genes are expressed in operons, and which are differentially expressed at low (4°C) or high (23°C) temperature. Approximately 55% of genes were found to be arranged in operons that range in length from 2 to 23 genes, and mRNA abundance tended to increase with operon length. Analysing microarray data previously obtained by others for Halobacterium salinarum revealed a similar correlation between operon length and mRNA abundance, suggesting that operons may play a similar role more broadly in the Archaea. More than 500 genes were differentially expressed at levels up to ≈ 24-fold. A notable feature was the upregulation of genes involved in maintaining RNA in a state suitable for translation in the cold. Comparison between microarray experiments and results previously obtained using proteomics indicates that transcriptional regulation (rather than translation) is primarily responsible for controlling gene expression in M. burtonii. In addition, certain genes (e.g. involved in ribosome structure and methanogenesis) appear to be regulated post-transcriptionally. This is one of few experimental studies describing the genome-wide distribution and regulation of operons in archaea.

Spontaneous supracondylar femoral fracture in an HIV patient in lotus position.

Bone disorders have been described in patients chronically infected with human immunodeficiency virus (HIV). A case of spontaneous supracondylar femoral fracture that occurred in a 58-year-old monk during meditation is reported. His AIDS disease was controlled with combination antiretroviral therapy. Vitamin D and calcium had been added 3yr before since osteoporosis was detected by dual-energy X-ray absorptiometry (DXA). At the time of the fracture, the patient was on treatment with 35mg every week of sodium risedronate, 1000mg of calcium, and 400IU of Vitamin D every day. Clinical use of DXA for HIV patients should be considered as a routine measure to help reducing risk for fractures.

Low bone mass prevalence, therapy type, and clinical risk factors in an HIV-infected Brazilian population.

Low bone mineral density (BMD) has been described in human immunodeficiency virus (HIV)-infected patients, but data on associated factors are still unclear, and to our knowledge, no reports are available in Brazil. Our goal was to evaluate BMD in HIV patients attending an outpatient clinic in Vitoria, Brazil. A sectional study was performed in 300 HIV-infected patients to measure BMD by dual-energy X-ray absorptiometry (DXA). Age, gender, anthropometric parameters, nadir and current CD4 cell count, HIV viral load, smoking habit, and current antiretroviral therapy (ART) associations were investigated by multivariable analysis. Based on World Health Organization T-score ranges, low BMD (T-score <-1.0 standard deviation [SD] in postmenopausal women and men aged 50 and older or Z-score <- 2.0 SD in premenopausal women and men below the age of 50) was detected in 54.7% (95% confidence interval: 49.1-60.3%) of the 300 enrolled patients. The observed median age was 46 yr (interquartile range: 39-52), 58% were male, 88.5% were on ART, and 21.4% smoked. The following factors were identified, by multiple logistic modeling, as being independently associated with low BMD: (1) male gender (4.6 [1.28-16.39]), (2) body mass index lower than 25 kg/m(2) (2.9 [1.31-6.49]), (3) menopause (13.4 [2.53-71.12]), and (4) HIV-1 undetectable viral load (7.9 [1.96-32.25]). Conversely, zidovudine (0.2 [0.04-0.85]) and nevirapine (0.1 [0.02-0.38]) use were inversely associated with low BMD. Low BMD was frequently found in our cohort of about 300 Brazilian HIV-infected subjects. This study supports the need for periodic DXA testing in HIV outpatient clinics.

Treatment of a post surgery defect of the lower lip: a case report.

We present the clinical case of a patient, CT of 35 years who came to our observation for the appearance of a recurrent mucocele on the lower lip. The mucocele or retention cyst is a benign lesion of minor salivary glands characterized by swelling, which can vary from a few millimeters to several centimeters, as determined by retention of secretion due to partial or total obstruction of an excretory duct. Current thinking is that the mucocele is formed due to traumatic events or inflammatory, malformation of the excretory duct or parenchyma of the minor salivary glands. Once framed the patient from a clinical point of view we performed surgery, which provides complete enucleation of the lesion by about 7 mm. The clinical suspicion was confirmed by histological diagnosis as extraductal mucocele. After about six months after surgery, at complete healing, resulted a residual imperfections with a loss of substance in the area. To eliminate this defect, poorly tolerated by the patient, we decided to use a filler of hyaluronic acid, which, although it is an absorbable material, results in an excellent appearance and does not expose to complications like the use of inducible permanent.

Network inference from population-level observation of epidemics.

Using the continuous-time susceptible-infected-susceptible (SIS) model on networks, we investigate the problem of inferring the class of the underlying network when epidemic data is only available at population-level (i.e., the number of infected individuals at a finite set of discrete times of a single realisation of the epidemic), the only information likely to be available in real world settings. To tackle this, epidemics on networks are approximated by a Birth-and-Death process which keeps track of the number of infected nodes at population level. The rates of this surrogate model encode both the structure of the underlying network and disease dynamics. We use extensive simulations over Regular, Erdos-Rényi and Barabási-Albert networks to build network class-specific priors for these rates. We then use Bayesian model selection to recover the most likely underlying network class, based only on a single realisation of the epidemic. We show that the proposed methodology yields good results on both synthetic and real-world networks.

Does chlorhexidine mouthwash reduce the rate of oral colonization bygram-negative bacteria in patients with chemotherapy? Aplacebo-controlled trial.

The presence of gram-negative bacteria in the oral cavity is an undesirable occurrence in patients undergoing chemotherapy. Our aim was to investigate the antibacterial effect of 0.12% chlorhexidine mouthwash in chemotherapypatients with a randomized, double-blind, placebo-controlled trial. There were no significant differences between oral colonization rates; there may be local factors that interfere with chlorhexidine activity.

Effectiveness of a new decisional algorithm in managing mandibular ameloblastomas: a 10-years experience.

We present a new treatment algorithm aimed to assist surgeons to develop a rational diagnostic protocol and establish effective conservative surgical management in patients with mandibular ameloblastoma. Fifteen consecutive cases treated by conservative management were reviewed. Data collected included age, sex, symptoms and signs at diagnosis, anatomical distribution of the lesions, numbers and types of operations, number of recurrences, and duration of follow-up post-operatively. Curettage was the first operation for all patients and they were closely followed-up post-operatively. During the follow-up period (4-10 years), small recurrences were diagnosed early in 7 patients who were treated by radical surgery including marginal or "box" resection. No further recurrences were observed after the second operation. When detected early, recurrences are small and surrounded by a large amount of uninvolved normal bone so it is possible to manage them with a radical resection, so lowering the risk of further recurrence and avoiding severe cosmetic and functional problems.

Experimental study of the strain rate dependence of a synthetic gel for ballistic blunt trauma assessment.

The mechanical characterization of a polymer gel used as reference backing material for blunt ballistic impact interpretation is performed at room temperature from quasi-static (0.002s-1) up to high strain rates (1500s-1). As very high strain tensile tests (350%) are conducted, an appropriate gripping device and particular strain measurement techniques are used, as well as high strain compressive tests (80%) based on retro lighting imaging. One major challenge is to carry out reliable compressive tests at high strain rates with polymeric split Hopkinson pressure bars using high-speed imaging and specific signal processing software. These mechanical tests provide a primary response to the strain rate dependence of the hyperelastic material behavior. Indeed, the material exhibits a higher stress response when the strain rate increases. Moreover, dynamic compression tests highlight a larger radial strain propagating along specimen axis with higher strain rates. This preliminary study on the characterization of the gel's mechanical behavior, constitutes an interesting step for an evaluation of human surrogate material. The extensive constitutive law can therefore be implemented for numerical simulations, with an aim of impact biomechanics analysis and body armor assessment.

Use of the PSA enhancer core element to modulate the expression of prostate- and non-prostate-specific basal promoters in a lentiviral vector context.

Composite promoters combining the prostate-specific antigen (PSA) enhancer core element with promoter elements derived from gene coding for human prostate-specific transglutaminase gene, prostate-specific membrane antigen gene, prostate-specific antigen, rat probasin or phosphoglycerate kinase were characterized for their ability to specifically express the enhanced green fluorescent protein (EGFP) gene in prostate versus non-prostate cancer cell lines when transferred with a human immunodeficiency virus-1-based lentiviral vector. By themselves minimal proximal promoter elements were found to inefficiently promote relevant tissue-specific expression; in all the vectors tested, addition of the PSA enhancer core element markedly improved EGFP expression in LnCaP, a cancer prostate cell line used as a model for prostate cancer. The composite promoter was inactive in HuH7, a hepatocarcinoma cell line used as a model of neighboring non-prostate cancer cells. Among the promoters tested, the combination of the PSA enhancer and the rat probasin promoter showed both high specificity and a strong EGFP expression. Neither a high viral input nor the presence of the cPPT/CTS sequence affected composite promoter behavior. Our data suggest that composite prostate-specific promoters constructed by combining key elements from various promoters can improve and/or confer tissue specific expression in a lentiviral vector context.

Photosensitizing activity of hematoporphyrin on Staphylococcus aureus cells.

The photosensitizing action of hematoporphyrin (Hp) on two Staphylococcus aureus strains was investigated to determine if the photoprocess induces in vivo damage in DNA in addition to that occurring at the level of the cytoplasmic membrane. The results obtained demonstrate that the photokilling is dependent on the Hp dose even though the two strains, having a similar Hp-binding capacity, show different levels of photosensitivity. The electrophoretic analysis of cytoplasmic membrane proteins and DNA (chromosomal and plasmidial) suggests that the membrane represents the primary target of the photoprocess, while the DNA, that is damaged both in vivo and in vitro only at relatively long irradiation time, might be a secondary target. Moreover, the photoprocess results in mutagenesis for Salmonella typhimurium tester strains. This information is particularly important in view of the potential use of photodynamic therapy for the treatment of microbial infections.

Demonstration of Chlamydia pneumoniae in atherosclerotic arteries from various vascular regions.

Chlamydia pneumoniae (CP) has been reported to be a pathogenic agent in the mechanism leading to atherosclerosis. The majority of available data is focused mainly on coronary artery disease whereas the distribution of CP in different areas, associated with atherosclerotic disorders, has not been completely clarified. In this study we investigated the presence of CP in atheromasic plaques from five different vascular areas (basilary artery, coronary artery, thoracic aorta, abdominal aorta, renal arteries) using nested polymerase chain reaction (PCR) and immunohistochemical staining (IHC), in order to establish the putative association of CP with atherosclerotic disease. The same atheromasic plaques were also tested for the presence of Helicobacter pylori (HP) and cytomegalovirus (CMV), other putative agents of atherosclerosis, using a nested PCR technique. Our data indicate that the presence of CP can be demonstrated in 100% of patients tested, considering globally the five areas of analysis. On the other hand the presence of HP has been demonstrated in four out of 18 patients (22.2%), and CMV only in three out of 18 (16.6%). Our results strongly suggest an association between CP and atherosclerosis and highlight the need for the detection of CP in multiple vascular areas of the same patient.

The metabolism of zearalenone in subcellular fractions from rabbit and hen hepatocytes and its estrogenic activity in rabbits.

The in vitro reduction of zearalenone (ZEN) by subcellular fractions from hen and rabbit hepatocytes clearly shows species-specific differences in the cofactor requirements, rate of metabolism and production of metabolites. The presence of NADH as cofactor in the reaction mixtures enhanced only the reducing activity of the microsomal fraction from rabbit hepatocytes, while NADPH enhanced the reducing activities of the cytosolic fraction from rabbit and both the microsomal and cytosolic fractions from hen hepatocytes. Furthermore, we observed that hen hepatocytes metabolize faster and produce beta-zearalenol (ZEL) as the major metabolite, whereas rabbit hepatocytes metabolize ZEN slowly and mainly into alpha-ZEL, the more uterotrophic metabolite. These last findings are closely related to the higher sensitivity to ZEN estrogenic effects observed in rabbits during the toxicity test involving p.o. administration of the mycotoxin to the animals at 3 dosage levels (0.1, 1, 2 mg/kg body wt).