Assessment of airborne mycoflora in critical areas of the Principal Hospital of Cumaná, state of Sucre, Venezuela

The study of the nosocomial infections of fungic origin has attained importance in the last years, due to the rise in the number of patients that are inmunocompromised and susceptible to suffer this kind of infection. The objective of the present study was to evaluate the frequency of filamentous fungi and yeast, present in the environment of the Intensive Care Unit, operating and newborn children rooms of the Hospital Universitario "Antonio Patricio de Alcalá" (HUAPA) from the city of Cumaná. Suere State, Venezuela. The recount of colony forming units/plate (UCF/plate) of the filamentous fungi and yeast was done in Petri plates with Sabouraud dextrose agar, which were exposed in the different studied areas. Eventually, the fungus colonies found were isolated and identified. The area that presented the highest average of UCF/plate was the Intensive Care Unit (9 UCF/plate). The isolated genus of filamentous fungus in higher proportion were Aspergillus (46.80%), Penicillium (19.19%) and Fusarium (11.06%). The isolated species with more frequency were Aspergillus niger (24.80%), Aspergillus flavus (10.54%) and Fusarium solani (9.52%). Rhodotorula glutinis was the isolated yeast with most frequency and different species of the genus Candida and the genus Criptococcus were isolated as well.     

Effects of flurbiprofen on CRP, TNF-α, IL-6, and postoperative pain of thoracotomy

Objective: The aims of this study were to evaluate serum levels of acute phase reactants, such as CRP and cytokines (TNF-α and IL-6) in patients who have undergone thoracotomy and to investigate the effects of flurbiprofen on postoperative inflammatory response.Methods: Forty patients undergoing posterolateral thoracotomy were randomly divided into 2 groups of 20 each. Control group received tramadol (4 x 100 mg) intravenously for four days, and flurbiprofen group received both tramadol (4 x 100 mg) and flurbiprofen (2 x 100 mg). Blood samples were collected before surgery and at the 3th and 168th hours after surgical procedure to measure serum CRP, IL-6, and TNF-α. Pain visual analog scales were recorded daily during the first four postoperative days. Spirometric measurement of forced expiratory volume in the first second (FEV 1) was done before and four days after the operation.Results: The serum CRP, IL-6, and TNF-α levels in both groups increased significantly at 3th hour after thoracotomy. Serum TNF-α levels did not differ significantly between the groups at postoperative 4th day. However, IL-6 and CRP were significantly lower in flurbiprofen group than in control group at the same day (p<0.05). Visual analog scale was significantly lower in flurbiprofen group at 6th, 12th, 48th, 72th, and 96th hours postoperatively (p<0.05). The patients receiving flurbiprofen had higher FEV 1 values when compared with control group at postoperative 4th day.Conclusions: Patients undergoing thoracotomy showed reduced postoperative pain, mean additional analgesic consumption, and serum IL-6 and CRP levels, when flurbiprofen was added to systemic analgesic therapy. Analgesia with anti-inflammatory drug may contribute to the attenuation of the postoperative inflammatory response and prevent postoperative pain in patients undergoing thoracotomy.     

Analysis of trajectories of eye,head, and hand movements for early diagnosis of Parkinson’s disease

Relationships between eye, head, and hand movements in patients with stages I–II Parkinson’s disease were studied using an original method. The tests for individual movements in patients and healthy individuals yielded similar results, while coordination test revealed significant differences. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 5, pp. 484–486, May, 2007     

Integration of two models, or dominance of one?

Hobbis and Sutton attempted to integrate Cognitive Behavior Therapy (CBT) with the Theory of Planned Behavior (TPB). The possibility of such an integration portends exciting opportunities since behavioral interventions have had limited impact on behavior change. The integration, however, may more easily occur if Hobbis and Sutton had selected a formulation of the TPB that incorporated emotional variables, which is a primary focus of CBT. Furthermore, more work may be necessary to integrate the specific cognitive constructs between CBT and the TPB. Empirical research will be necessary to validate that the integration occurred in a meaningful way.     

Identification and characterization of the ribosome-associated protein, HrpA, of Bacillus Calmette-Guérin

HrpA was found as a ribosome-associated protein which appeared in heat-stressed Mycobacterium bovis Bacillus Calmette-Guérin. Here, we have studied the function of HrpA in vitro. HrpA is a heat shock protein belonging to a small heat shock protein family. The putative molecular mass was 17784.86 kDa. Recombinant HrpA formed large complexes of nonamer or dodecamer. HrpA prevented the aggregation of enzymes under heat shock conditions, and it formed stable complexes with partially denatured enzymes. HrpA was induced temporarily by oxygen repletion after anaerobic condition.     

Study of Anti-Inflammatory Action of Aurothiomalate,an Inhibitor of NF-κB

We compared the effects of NF-κB inhibitor aurothiomalate and voltaren on NO production by mouse macrophages in vitro, their ability to cause local edema at the site of injection, and their effect on carrageenan-induced inflammation. High concentrations of aurothiomalate reduced NO production, while in low concentrations both aurothiomalate and voltaren stimulated this process. When injected into mouse footpad, aurothiomalate in a dose >1 mM and voltaren in a dose >1.6 μM induce paw edema. Both compounds suppressed carrageenan-induced inflammation, but the efficacy of aurothiomalate 2-fold exceeded that of voltaren.     

Prevalence of childhood asthma,rhinitis, and eczema in the Ternopil region of Ukraine – results of BUPAS study

PurposeThe aim of the study was to estimate the prevalence of allergic diseases and symptoms in children of the Ternopil Region (Ukraine) and to explore their familial and environmental correlates.Material/MethodsA cross-sectional study based on parental answers to a respiratory questionnaire based on ISAAC that included 4871 urban and rural children aged 6–14 years. Association of physician-made diagnoses and symptoms with environmental factors was examined by means of multivariate logistic regression.ResultsIncreased risk of asthma (1.7%) was associated with urban residence (OR=1.8; p=0.04) and high parental education (OR=1.8; p=0.02); spastic bronchitis (6.2%) with parental allergy (OR=1.3; p=0.03); atopic eczema (6.2%) with younger age (OR=1.3; p=0.03), high parental education (OR=1.3; p=0.03), parental allergy (OR=1.4; p=0.02), tobacco smoke at home (OR=0.7; p=0.01) and household density (OR=0.6; p=0.001); diagnosis of unspecified allergic sensitization (11.8%) was related to high parental education (OR=1.2; p=0.03), parental employment (OR=0.8; p=0.02) and pets at home (OR=1.2; p=0.06). Symptoms of chest wheezing (11.5%) were related to tobacco smoke at home (OR=0.8; p=0.06). Attacks of dyspnea (7.3%) were related to parental allergy (OR=1.4; p=0.007), and type of heating (OR=1.7; p=0.04). Hay fever symptoms (5.7%) were related to younger age (OR=1.3; p=0,01) and urban residence (OR=2.0; p<0.0001).ConclusionsExcept for asthma the prevalence of allergic diseases and symptoms as well as their correlates in children of Ternopil are similar to other estimates obtained in Eastern Europe. Low prevalence of asthma and relatively frequent occurrence of spastic bronchitis may suggest substantial underdiagnosis of childhood asthma.     

Roles of RseB, σE,and DegP in Virulence and Phase Variation of Colony Morphotype of Vibrio vulnificus

Vibrio vulnificus is an estuarine bacterium capable of causing serious and often fatal wound infections and primary septicemia. We used alkaline phosphatase insertion mutagenesis to identify genes necessary for the virulence of this pathogen. One mutant had an in-frame fusion of ′phoA to the gene encoding RseB, a periplasmic negative regulator of the alternative sigma factor σ^E. σ^E controls an extensive regulon involved in responding to cell envelope stresses. Colonies of the rseB mutant were less opaque than wild-type colonies and underwent phase variation between translucent and opaque morphologies. rseB mutants were attenuated for virulence in subcutaneously inoculated iron-dextran-treated mice. To obtain insight into the role of rseB and the extracytoplasmic stress response in V. vulnificus, mutants with defined mutations in rseB and two important members of the extracytoplasmic stress regulon, rpoE and degP, were constructed for analysis of virulence, colony morphology, and stress-associated phenotypes. Deletion of rseB caused reversible phase variation in the colony morphotype that was associated with extracellular polysaccharides. Translucent and transparent morphotype strains were attenuated for virulence. rpoE and degP deletion mutants were sensitive to membrane-perturbing agents and heat but were not significantly attenuated for V. vulnificus virulence in mice. These results reveal complex relationships between regulation of the extracytoplasmic stress response, exopolysaccharides, and the virulence of V. vulnificus.Vibrio vulnificus is a gram-negative estuarine bacterium responsible for severe opportunistic infections (for a review, see reference 17). Ingestion of raw contaminated seafood can lead to septicemia in susceptible patients, while contact with contaminated seawater or seafood can cause wound infection, which may progress to necrotizing fasciitis and sepsis. Mortality rates for sepsis and wound infection can be as high as 75% and 50%, respectively. Predisposing conditions for septicemia include liver disease, cirrhosis, hemochromatosis, diabetes, and immune compromise, while wound infection can occur in otherwise healthy persons.Several virulence factors have been identified for V. vulnificus, most notably the antiphagocytic capsule (55, 65), RtxA toxin (26, 28, 32), and iron acquisition systems (31, 64). For a review, see reference 17. However, much is yet to be discovered, particularly the mechanisms of extreme tissue damage and rapid growth in host tissues (17). To examine these traits, we focused on the factors that are localized to the bacterial cell surface or are secreted into the extracellular space, considering that most virulence factors are exported to interact with the host. Alkaline phosphatase (phoA) mutagenesis is a useful tool for identifying genes encoding exported products (33), based on the principle that alkaline phosphatase is active only when it is exported beyond the bacterial cytoplasm. Randomly generated phoA gene fusions, most often generated via TnphoA (33), must be in genes encoding exported proteins to have enzyme activity detected by plating on the chromogenic substrate 5-bromo-4-chloro-3-indolylphosphate (BCIP). In our studies, TnphoA did not work effectively in V. vulnificus for unknown reasons. We therefore created a mini-Tn5 transposon-based ′phoA delivery system, miniTn5phoA (8), that works well in V. vulnificus.Using this method, we identified a phoA mutant that had an in-frame fusion of ′phoA to the gene encoding RseB, a periplasmic negative regulator of sigma E (σ^E) activity. The rseB mutant exhibited several interesting phenotypes, including phase variation between translucent and opaque colony morphologies and attenuated virulence. σ^E is an alternative RNA polymerase sigma factor that controls an extensive regulon involved in responding to cell envelope stresses (48). This response, termed the extracytoplasmic stress response (ESR), is essential for maintaining the envelope integrity of gram-negative bacteria under certain stress conditions (for a review, see reference 48). Because rseB is involved in the ESR, we determined the role of the σ^E-mediated ESR in V. vulnificus. We also investigated the possible reasons for the translucent morphology of RseB variants by comparing these variants with an acapsular translucent mutant of V. vulnificus. This study uncovered a possible role for RseB in phase variation of extracellular polysaccharide (EPS) expression and is the first study to investigate the role of the ESR in the virulence of V. vulnificus.     

Transmission heterogeneities,kinetics, and controllability of SARS-CoV-2

A long-standing question in infectious disease dynamics concerns the role of transmission heterogeneities,which are driven by demography,behavior,and interventions.On the basis of detailed patient and contact-tracing data in Hunan,China,we find that 80% of secondary infections traced back to 15% of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)primary infections,which indicates substantial transmission heterogeneities.Transmission risk scales positively with the duration of exposure and the closeness of social interactions and is modulated by demographic and clinical factors.     

The nexus of aβ, aging, and sleep

Roh et al. report a positive feedback loop between sleep-wake irregularities and aggregation of β-amyloid peptide, suggesting that sleep alterations could be an early event in Alzheimer's disease.     

Compartmentalization of cyclic nucleotide signaling: a question of when, where, and why?

Preciseness of cellular behavior depends upon how an extracellular cue mobilizes a correct orchestra of cellular messengers and effector proteins spatially and temporally. This concept, termed compartmentalization of cellular signaling, is now known to form the molecular basis of many aspects of cellular behavior in health and disease. The cyclic nucleotides cyclic adenosine monophosphate and cyclic guanosine monophosphate are ubiquitous cellular messengers that can be compartmentalized in three ways: first, by their physical containment; second, by formation of multiple protein signaling complexes; and third, by their selective depletion. Compartmentalized cyclic nucleotide signaling is a very prevalent response among all cell types. In order to understand how it becomes relevant to cellular behavior, it is important to know how it is executed in cells to regulate physiological responses and, also, how its execution or dysregulation can lead to a pathophysiological condition, which forms the scope of the presented review.     

The Correlation of Salvia miltiorrhiza Extract–Induced Regulation of Osteoclastogenesis with the Amount of Components Tanshinone I,Tanshinone IIA,Cryptotanshinone, and Dihydrotanshinone

Tanshinone I, tanshinone IIA, cryptotanshinone, and dihydrotanshinone are compounds that have been isolated from the root of Salvia miltiorrhiza (SM), which is also known as “Danshen.” The SM extract has been used successfully in China for treating postmenopausal syndrome. Furthermore, it was previously reported that SM had inhibitory effect on osteoporosis in ovariectomized rats. Another study reported that the four components, tanshinone I, tanshinone IIA, cryptotanshinone, and dihydrotanshinone, prevented osteoclast function in an in vitro system. However, there are no reports of a correlation between SM and its components on osteoporosis and osteoclast function. This study was undertaken to examine the effect of SM on osteoclastogenesis and osteoblast differentiation, which are two important markers of the bone physiology. Through a rapid, sensitive and specific isocratic liquid chromatography/tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantitative determination of four diterpenoids, tanshinone I, tanshinone IIA, cryptotanshinone, and dihydrotanshinone in SM, the authors tried to correlate the amount of tanshinone compounds in SM into the antiosteoclast activity. The SM fraction (methanol and ethanol isolated) with a low concentration of tanshinone IIA (1 μg/mL) had no effect on the alkaline phosphotase activity (osteoblast differentiation), but completely inhibited osteoclastogenesis. Although the tanshinone compound itself showed similar effects, the concentrations of commercially available tanshinone (diterpenoids, tanshinone I, tanshinone IIA, cryptotanshinone, and dihydrotanshinone) needed for antiosteoclast activity was almost 1000 times more than that of tanshinone in SM fraction. This suggests that there are other unknown compounds in the SM extract that have a synergistic effect with tanshinone. These results also suggest that tanshinone can be a good marker compound to explain the antiosteoporotic function of SM.     

Macrophage Uptake,Intracellular Localization,and Degradation of Poly-γ-d-Glutamic Acid,the Capsular Antigen of Bacillus anthracis

Bacillus anthracis is surrounded by a capsular polypeptide composed of poly-γ-d-glutamic acid (PGA). This antiphagocytic capsule is an essential virulence factor and is shed into body fluids during a murine model of pulmonary anthrax. Our previous studies of a murine model for antigen clearance showed that purified PGA accumulates in the liver and spleen, most notably in splenic macrophages and the Kupffer cells and sinusoidal endothelial cells of the liver. Although the tissue and cellular depots have been identified, there is little known about the uptake and intracellular fate of PGA. As a consequence, we examined the cellular uptake and organelle localization of PGA in the murine macrophage-like cell line J774.2. We found that PGA binds to and is internalized by J774.2 cells and accumulates in CD71 transferrin receptor-positive endosomes. The receptor-mediated endocytosis inhibitors amantadine and phenylarsine oxide inhibited the binding and uptake of PGA in these cells. Cytochalasin D and vinblastine, actin and microtubule inhibitors, respectively, failed to completely inhibit binding and uptake. Finally, we found that PGA is degraded in J774.2 cells starting 4 h after uptake, with continued degradation occurring for at least 24 h. This degradation of PGA may explain the rapid clearance of PGA that is observed in vivo compared to the slow clearance noted with capsular polysaccharides.Bacillus anthracis, the causative agent of anthrax, is surrounded by an antiphagocytic capsule that is an essential virulence factor (7, 13, 32). The capsule is unusual because it is composed of poly-γ-d-glutamic acid (PGA) (12); encapsulated bacteria are typically surrounded by a polysaccharide capsule. PGA is shed into body fluids in high concentrations during a murine model of pulmonary anthrax (15). However, our previous studies also found that purified PGA is rapidly cleared from the blood (24 h) in mice (28). This rapid clearance contrasts with the much slower in vivo clearance of capsular polysaccharides which remain in the blood for several days (11, 28). PGA is also rapidly cleared from tissues, with the complete clearance of measurable antigen after 21 days, and excreted into the urine as fragments of heterogeneous size (28). In contrast, Kaplan et al. found that pneumococcal polysaccharide remains in murine tissues up to 75 days (14).Previous studies of a murine model of antigen clearance showed that purified PGA accumulates in the liver, specifically in the Kupffer cells and the sinusoidal endothelial cells (28), with smaller amounts of PGA in the splenic macrophages. However, the intracellular location and kinetics for the uptake of PGA by host cells are not known. Macrophages ingest particles and macromolecules via several different pathways, including phagocytosis, pinocytosis, and receptor-mediated endocytosis (5). Although each of these pathways may be unique to the object being endocytosed, once inside, the general trafficking pathways are similar. Typically, molecules are endocytosed and taken from early endosomes to late endosomes and onto the lysosome for degradation (22). Although most molecules follow this pathway, some proteins, including transferrin, are recycled back to the plasma membrane via the recycling endosomal pathway (1). In addition, some proteins, such as cholera toxin, undergo retrograde transport from the early endosomes, back to the trans-Golgi network (25, 26).In an attempt to better understand the intracellular trafficking of PGA, we examined the kinetics for uptake and the intracellular location of PGA in the macrophage-like cell line J774.2. In addition, microtubule, actin, and receptor-mediated endocytosis inhibitors were used to examine the potential mechanisms for PGA binding and uptake. Glucuronoxylomannan (GXM), the capsular polysaccharide from Cryptococcus neoformans, was used as a model for comparison of the uptake of polypeptide versus polysaccharide capsular antigens. Our results show that PGA is taken up and trafficked through the recycling endosomes; such transport can be blocked by inhibitors of receptor-mediated endocytosis.     

Expression of E-cadherin, α-catenin, and β-catenin in tubulolobular carcinoma of the breast

Tubulolobular carcinoma (TLC) of the breast is a rare subtype of breast carcinoma categorized by Fisher et al. (Hum Pathol 8:679–683, 1977) as a tubular variant of lobular carcinoma. E-cadherin is a transmembrane glycoprotein, and complete loss of E-cadherin expression has been observed in invasive lobular carcinoma. Ductal carcinoma retains at least some expression of E-cadherin. Moreover, the adhesive function of E-cadherin is dependent on the integrity of the catenin components, which link E-cadherin to the actin filaments. In order to achieve improved categorization of TLC, we decided to investigate both E-cadherin and the catenins in TLCs and invasive lobular carcinomas. We reviewed all 1,430 cases of primary breast carcinoma that were surgically resected at Saitama Medical Center, Saitama Medical School, and at Saitama Red Cross Hospital between 1990 and 2005. Among these, 16 cases of TLC were reported retrospectively. The results were compared with those of 20 cases of invasive lobular carcinomas that were included as controls. Tumor tissue was immunostained for E-cadherin, α-catenin, and β-catenin. The presence of immunoreactivity in the TLC was seen in 12 (75%) cases for E-cadherin, in 8 (50%) cases for α-catenin, and in 10 (62.5%) cases for β-catenin. However, plasma-membrane-associated staining for E-cadherin, α-catenin, and β-catenin was completely absent in invasive lobular carcinomas. These results suggest the possibility that TLCs are not a variant of lobular carcinoma, but rather ductal carcinomas with a lobular growth pattern.