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There remains a critical need for new antibiotics against multi-drug-resistant Gram-negative bacteria, a major global threat that continues to impact mortality rates. Lipoprotein signal peptidase II is an essential enzyme in the lipoprotein biosynthetic pathway of Gram-negative bacteria, making it an attractive target for antibacterial drug discovery. Although natural inhibitors of LspA have been identified, such as the cyclic depsipeptide globomycin, poor stability and production difficulties limit their use in a clinical setting. We harness computational design to generate stable de novo cyclic peptide analogues of globomycin. Only 12 peptides needed to be synthesized and tested to yield potent inhibitors, avoiding costly preparation of large libraries and screening campaigns. The most potent analogues showed comparable or better antimicrobial activity than globomycin in microdilution assays against ESKAPE-E pathogens. This work highlights computational design as a general strategy to combat antibiotic resistance.

This study aimed to evaluate the effect of increasing levels of red propolis extract (RPE) in the diet of confined sheep on performance and histomorphometric parameters of rumen and intestine and histopathological parameters of liver and kidney. Thirty-five male sheep (17.08 ± 2.36 kg) were used, distributed in a completely randomized design, with five treatments (0, 7, 14, 21, and 28 mL day -1 RPE) and seven replications, submitted to 68 days of experiment. At the end of the experimental period, the animals were euthanized, and samples of rumen, intestine, liver, and kidney were collected to histomorphometry and histopathology analyzes. Higher RPE inclusions (21 and 28 mL day -1 ) maintained dry matter intake and increased total weight (5.78 x 6.14 and 6.95 kg, respectively) gain up to 20.24%. In the rumen, the inclusion of RPE led to an increase in the thickness of the epithelium and the highest level also increased the thickness of the keratinized portion of this epithelium (21.71 x 32.15 μm). The level of 21 mL day-1 provided larger ruminal papillae (1620.68 x 1641.70 μm) and greater ruminal absorption area (561791.43 x 698288.50 μm 2 ). In intestine 21 and 28 mL-1 of RPE provided greater mucosal thickness (468.54 x 556.20 and 534.64 μm), higher goblet cell index (23.32 x 25.82 and 25.64) and higher hepatic glycogen index (1.47 x 1.64 and 1.62), supporting higher nutrients absortion and glicogenolise and intestinal health, corroborating the weight gain indices. The inclusion of RPE did not cause renal histopathological lesions. Therefore, levels of 21 and 28 mL day-1 of RPE can be used in sheep diets, promoting greater final weight gain, causing positive histomorphological changes in the rumen, intestine and liver, without causing kidney or liver damage., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Attachment of Staphylococcus aureus to human skin corneocyte cells plays a critical role in exacerbating the severity of atopic dermatitis (AD). Pathogen-skin adhesion is mediated by bacterial cell-surface proteins called adhesins, including fibronectin-binding protein B (FnBPB). FnBPB binds to corneodesmosin (CDSN), a glycoprotein exposed on AD patient corneocytes. Using single-molecule experiments, we demonstrate that CDSN binding by FnBPB relies on a sophisticated two-site mechanism. Both sites form extremely strong bonds with binding forces of ∼1 and ∼2.5 nN albeit with faster dissociation rates than those reported for homologues of the adhesin. This previously unidentified two-binding site interaction in FnBPB illustrates its remarkable variety of adhesive functions and is of biological significance as the high strength and short bond lifetime will favor efficient skin colonization by the pathogen., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Colonisation of humans by Staphylococcus aureus is a major risk factor for infection, yet the bacterial and host factors involved are not fully understood. The first step during skin colonisation is adhesion of the bacteria to corneocytes in the stratum corneum where the cornified envelope protein loricrin is the main ligand for S. aureus. Here we report a novel loricrin-binding protein of S. aureus, the cell wall-anchored fibronectin binding protein B (FnBPB). Single-molecule force spectroscopy revealed both weak and ultra-strong (2 nN) binding of FnBPB to loricrin and that mechanical stress enhanced the strength of these bonds. Treatment with a peptide derived from fibrinogen decreased the frequency of strong interactions, suggesting that both ligands bind to overlapping sites within FnBPB. Finally, we show that FnBPB promotes adhesion to human corneocytes by binding strongly to loricrin, highlighting the relevance of this interaction to skin colonisation., (© 2022. The Author(s).)

Staphylococcus aureus colonizes the skin of the majority of patients with atopic dermatitis (AD), and its presence increases disease severity. Adhesion of S. aureus to corneocytes in the stratum corneum is a key initial event in colonization, but the bacterial and host factors contributing to this process have not been defined. Here, we show that S. aureus interacts with the host protein corneodesmosin. Corneodesmosin is aberrantly displayed on the tips of villus-like projections that occur on the surface of AD corneocytes as a result of low levels of skin humectants known as natural moisturizing factor (NMF). An S. aureus mutant deficient in fibronectin binding protein B (FnBPB) and clumping factor B (ClfB) did not bind to corneodesmosin in vitro. Using surface plasmon resonance, we found that FnBPB and ClfB proteins bound with similar affinities. The S. aureus binding site was localized to the N-terminal glycine-serine-rich region of corneodesmosin. Atomic force microscopy showed that the N-terminal region was present on corneocytes containing low levels of NMF and that blocking it with an antibody inhibited binding of individual S. aureus cells to corneocytes. Finally, we found that S. aureus mutants deficient in FnBPB or ClfB have a reduced ability to adhere to low-NMF corneocytes from patients. In summary, we show that FnBPB and ClfB interact with the accessible N-terminal region of corneodesmosin on AD corneocytes, allowing S. aureus to take advantage of the aberrant display of corneodesmosin that accompanies low NMF in AD. This interaction facilitates the characteristic strong binding of S. aureus to AD corneocytes., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Quinoline and its derivatives comprise an important group of heterocyclic compounds that exhibits a wide range of pharmacological properties such as antibacterial, antiviral, anticancer, antiparasitic, anti-Alzheimer and anticholesterol. The quinoline nucleus is found in the structure of many drugs and rational design in medicinal chemistry for the discovery of novel bioactive molecules. Persistent efforts have been made over the years to develop novel congeners with superior biological activities and minimal potential for undesirable side effects. This review highlights some discoveries on the development of quinoline-based compounds in recent years (2013-2019), focusing on their biological activities, including anticancer, antitubercular, antimalarial, anti-ZIKV, anti-DENV, anti- Leishmania and anti-Alzheimer's disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Staphylococcus aureus is one of the major causes of bloodstream infections (BSI) worldwide, representing a major challenge for public health due to its resistance profile. Higher vancomycin minimum inhibitory concentrations (MIC) in S. aureus are associated with treatment failure and defining optimal empiric options for BSIs in settings where these isolates are prevalent is rather challenging. In silico pharmacodynamic models based on stochastic simulations (Monte Carlo) are important tools to estimate best antimicrobial regimens in different scenarios. We aimed to compare the pharmacodynamic profiles of different antimicrobials regimens for the treatment of S. aureus BSI in an environment with high vancomycin MIC., Methods: Steady-state drug area under the curve ratio to MIC (AUC/MIC) or the percent time above MIC (fT > MIC) were modeled using a 5000-patient Monte Carlo simulation to achieve pharmacodynamic exposures against 110 consecutive S. aureus isolates associated with BSI., Results: Cumulative fractions of response (CFRs) against all S. aureus isolates were 98% for ceftaroline; 79% and 92% for daptomycin 6 mg/kg q24h and for the high dose of 10 mg/kg q24h, respectively; 77% for linezolid 600 mg q12h when MIC was read according to CLSI M100-S26 instructions, and 64% when MIC was considered at the total growth inhibition; 65% and 86% for teicoplanin, three loading doses of 400 mg q12 h followed by 400 mg q24 h and for teicoplanin 400 mg q12 h, respectively; 61% and 76% for vancomycin 1000 mg q12 h and q8 h, respectively., Conclusions: Based on this model, ceftaroline and high-dose daptomycin regimens delivered best pharmacodynamic exposures against S. aureus BSIs. Teicoplanin higher dose regimen achieved the best CFR (86%) among glycopeptides, although optimal threshold was not achieved, and vancomycin performance was critically affected by the S. aureus vancomycin MIC ≥2 mg/L. Linezolid effectiveness (CFR of 73%) is also affected by high prevalence of isolates with linezolid MIC ≥2 mg/L. These data show the need to continually evaluate the pharmacodynamic profiles of antimicrobials for empiric treatment of these infections.

β-lactam antibiotics are excellent drugs for treatment of staphylococcal infections, due to their superior efficacy and safety compared to other drugs. Effectiveness of β-lactams is severely compromised due to resistance, which is widespread among clinical strains of Staphylococcus aureus . β-lactams inhibit bacterial cells by binding to penicillin binding proteins (PBPs), which perform the penultimate steps of bacterial cell wall synthesis. Among PBPs of S. aureus , PBP2a has received the most attention for the past several decades due to its preeminent role in conferring both high-level and broad-spectrum resistance to the entire class of β-lactam drugs. Studies on PBP2a have thus unraveled incredible details of its mechanism of action. We have recently identified that an uncanonical, low molecular weight PBP of S. aureus , PBP4, can also provide high-level and broad-spectrum resistance to the entire class of β-lactam drugs at a level similar to that of PBP2a. The role of PBP4 has typically been considered not so important for β-lactam resistance of S. aureus , and as a result its mode of action remains largely unknown. In this article, we review our current knowledge of PBP4 mediating β-lactam resistance in S. aureus .

Penicillin binding protein 4 (PBP4) can provide high-level β-lactam resistance in Staphylococcus aureus A series of missense and promoter mutations associated with pbp4 were detected in strains that displayed high-level resistance. We show here that the missense mutations facilitate the β-lactam resistance mediated by PBP4 and the promoter mutations lead to overexpression of pbp4 Our results also suggest a cooperative interplay among PBPs for β-lactam resistance., (Copyright © 2017 American Society for Microbiology.)

Penicillin-binding protein 4 (PBP4), a nonessential, low-molecular-weight penicillin-binding protein of Staphylococcus aureus , has been implicated in low-level resistance to β-lactam antibiotics, although the mechanism is unknown. Mutations in PBP4 and its promoter were identified in a laboratory-generated mutant strain, CRB, which expresses high-level resistance to β-lactams, including resistance to the new-generation cephalosporins active against methicillin-resistant strains of S. aureus These mutations did not appreciably alter the β-lactam antibiotic binding affinity of purified recombinant mutant PBP4 compared to that of wild-type PBP4. Compared to the susceptible parent strain, COLnex, the CRB strain produces a highly cross-linked cell wall peptidoglycan, indicative of increased transpeptidase activity. The pbp4 promoter mutation of CRB was associated with greatly increased amounts of PBP4 in membranes compared to those in the COLnex parent. Replacement of the native promoter of COLnex with the mutant promoter of CRB resulted in increased amounts of PBP4 in membranes and a highly cross-linked cell wall. PBP4 can be repurposed to provide essential transpeptidase activity in vivo and confer high-level resistance to β-lactam antibiotics, such as ceftobiprole and ceftaroline., (Copyright © 2017 American Society for Microbiology.)

Staphylococcus aureus is an important cause of bloodstream infections. Therefore, the main purpose of this work was to characterize a collection of 139 S. aureus isolates from bloodstream infections in two public hospitals in relation to their antimicrobial susceptibility profile, staphylococcal cassette chromosome mec types, and clonal relationship. Methicillin resistance and resistance to other 12 agents were accessed by the disk diffusion test. Minimum inhibitory concentration to mupirocin was also determined. The SCCmec types were accessed by multiplex PCR, and the clonal relationship was determined by pulsed field gel electrophoresis method and restriction modification system characterization. Besides, multilocus sequence typing was performed for representative methicillin-resistant S. aureus isolates. The military hospital showed a dissemination of the New York/Japan (USA100/ST5/CC5/SCCmecII) lineage associated to multidrug resistance, including mupirocin resistance, and the teaching hospital presented polyclonal and non-multidrug resistant MRSA isolates. Complete substitution of the Brazilian endemic clone by other lineages was found in both hospitals. These findings can highlight differences in policy control and prevention of infections used in the hospitals and a change in the epidemiological profile of MRSA in Brazilian hospitals, with the replacement of BEC, a previously well-established clone, by other lineages., (Copyright © 2016 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.)

This study analyzed clinical and microbiological characteristics of heteroresistant (hVISA) and vancomycin-intermediate Staphylococcus aureus (VISA) from bloodstream infections (BSI) in a Brazilian teaching hospital, between 2011 and 2013. Minimum inhibitory concentrations (MIC) of antimicrobials were determined by broth microdilution method and SCCmec was detected by PCR. Isolates with a vancomycin MIC ≥ 2mg/L were cultured on BHI agar with 3, 4 or 6 mg/L (BHIa3, BHIa4 or BHIa6) of vancomycin and BHIa4 with casein (BHIa4ca). Macromethod Etest® and Etest® Glicopeptides Resistance Detection were also used. VISA and hVISA isolates were confirmed by the population analysis profile then typed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing. Medical data from the patients were obtained from their medical records. Among 110 consecutive isolates, 31 (28%) were MRSA and carried the SCCmec type II (15 isolates) or IV (16 isolates). Vancomycin MIC50 and MIC90 were 1 and 2 mg/L, respectively. MRSA isolates had increased non-susceptibility to daptomycin (p = 0.0003). Six (5%) isolates were VISA, four of which were MRSA, three SCCmec type II/USA100/ST5 and one type IV/USA800/ST3192. One MRSA SCCmec II isolate grew on agar BHIa3, BHIa4 and BHIa4ca, and it was confirmed as hVISA. Among the six VISA isolates, five (83%) grew on BHIa3 and three (50%) on BHI4ca. Four of the six VISA isolates and the one hVISA isolate were from patients who had undergone dialysis. Thus, a possible dissemination of the SCCmec II/USA100/ST5 lineage may have occurred in the hospital comprising the VISA, hVISA and daptomycin non-susceptible S. aureus Brazilian isolates from health care associated bloodstream infections., Competing Interests: The authors have declared that no competing interests exist.

Background: The gold standard for treatment of soft tissue sarcomas (STS) includes wide local excision and limb salvage surgery. There is currently a lack of reports on the effectiveness of these techniques in a resource-poor setting with a lack of access to imaging and adjuvant therapies. This article reports the experience and outcome of patients presenting with STS to the Children's Surgical Centre (CSC), Phnom Penh, Cambodia., Methods: Patients with a diagnosis of STS and the operations they received were retrospectively sourced from the CSC database. Follow-up data were obtained through a telephone questionnaire and home visits., Results: Forty STS patients were identified. Definitive surgery was performed in 31 cases, the majority receiving initial local excision of the lesion (19/31), some went on to have secondary amputations (5/19), and the rest had primary amputation (12/31). Eight patients suffered perioperative complications: 6 had infections, 1 haemorrhage, and 1 patient suffered from prolonged pain. Follow-up information was available for 25 patients, 8 of whom survived whilst 17 had died. Two of the deceased and 2 of the surviving patients had received adjuvant therapy. Seven survivors reported that they had resumed employment. Estimated average survival for STS in Cambodia was 25 months with a 58 % 1-year survival rate in treated cases., Conclusions: Despite the loss to follow-up, some STS patients in Cambodia have been successfully managed by the CSC. An evolving increase in survival will hopefully be seen as access to adjuvant therapies and imaging technology improves.

Staphylococcus aureus is an important cause of both hospital- and community-associated methicillin-resistant S. aureus (MRSA) infections worldwide. β-Lactam antibiotics are the drugs of choice to treat S. aureus infections, but resistance to these and other antibiotics make treatment problematic. High-level β-lactam resistance of S. aureus has always been attributed to the horizontally acquired penicillin binding protein 2a (PBP 2a) encoded by the mecA gene. Here, we show that S. aureus can also express high-level resistance to β-lactams, including new-generation broad-spectrum cephalosporins that are active against methicillin-resistant strains, through an uncanonical core genome-encoded penicillin binding protein, PBP 4, a nonessential enzyme previously considered not to be important for staphylococcal β-lactam resistance. Our results show that PBP 4 can mediate high-level resistance to β-lactams., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

The isolation of mannitol-negative methicillin-resistant Staphylococcus aureus from nasal swabs is reported. Among the 59 isolates, 9 (15%) isolates were mannitol-negative; all of these isolates were categorized as staphylococcal cassette chromosome mec (SCCmec) type IVa. This report emphasizes that mannitol fermentation on mannitol salt agar should not be used as the sole criterion when screening nasal swab specimens for S. aureus.

Background: Daptomycin is an alternative option for the treatment of catheter-related bloodstream-infections caused by methicillin-resistant Staphylococcus aureus. This study reports a case of a daptomycin and methicillin-resistant Staphylococcus aureus isolate recovered from the blood of a Brazilian patient undergoing hemodialysis., Case Presentation: A 64-year-old white male patient suffering from diabetes mellitus, systolic hypertension, heart disease with a coronary stent, obesity and chronic renal failure and on use of permcath catheter developed a catheter-related bloodstream-infection by a daptomycin-methicillin-resistant Staphylococcus aureus isolate after one month of daptomycin therapy. The isolate was identified as the SCCmec II/USA100/sequence type 5 lineage by molecular techniques., Conclusions: In this work we described a Brazilian patient with bloodstream infection caused by a daptomycin and methicillin-resistant Staphylococcus aureus belonging to the lineage USA100/sequence type 5. Our case highlights the careful management of bloodstream infections and the importance of the judicious use of antimicrobials due the possibility of daptomycin-resistance developing among S. aureus isolates, especially in patients under hemodialysis, which are frequently exposed to vancomycin and daptomycin therapy.

Hospital associated methicillin-resist Staphylococcus aureus has long been associated to outbreaks in the hospital environment. In this work, we investigated an outbreak of Hospital associated methicillin-resist Staphylococcus aureus carrying the Panton-Valentine leukocidin gene, which occurred in a large community hospital in Rio de Janeiro, Brazil.

To evaluate the relationship between physical activity with co morbidities and health-related quality of life in type 2 diabetic patients with and without restless legs syndrome (RLS). This is an observational study, set at tertiary care diabetic outpatient clinic, where 200 consecutive type 2 diabetic patients and 47 controls participated. Physical activity level was established by the International Physical Activity Questionnaire (IPAQ) and RLS diagnosis and RLS severity were established using the criteria defined by the International Restless Legs Syndrome Study Group; excessive daytime sleepiness was evaluated by the Epworth Sleepiness Scale, quality of sleep by the Pittsburgh Sleep Quality Index and Health-Related Quality of Life by the Short-Form Health Survey (SF-36). Depressive symptoms were investigated by Beck Depression Inventory (BDI- II). Among all diabetic patients (58 % women, mean age 52.7 ± 5.7), disease duration varied from 1 to 30 years (11.7 ± 7.5). Diabetic patients had more hypertension (76 %), peripheral neuropathy (65 %), and depressive symptoms (31 %) than controls; no gender differences were found between cases with and without depressive symptoms. RLS patients (72 % female) had worse quality of sleep. With regards to the quality of life domains, more active RLS diabetic patients had better perception of functional capacity, physical limitation, pain, and general health state (p < 0.05). RLS symptom severity did not vary according to physical activity (IPAQ level). This study shows that the physical activity is associated with a better perception of functional capacity, physical limitation, and pain in diabetic patients with RLS; thus a more active lifestyle should be encouraged.

Anterior dislocation of the native hip joint is an uncommon presentation accounting for around 15% of all hip dislocations. It is usually the result of a high-energy impact in circumstances such as a motor vehicle accident or a fall from a significant height. A delay in relocation of more than 6 h has been associated with a high risk of avascular necrosis of the femoral head. We report the case of a 75-year-old man who suffered an anterior dislocation of his native hip following a fall from a standing height, associated with an acute cerebrovascular stroke. There was significant delay in the recognition of the dislocation due to the coexistent signs of the stroke. This case illustrates that hip dislocation can occur following a low-energy mechanism of injury with the possibility of serious long-term consequences if it is not promptly recognised and treated.

Introduction: Soft tissue reactions following metal-on-metal (MoM) arthroplasty of the hip have been under considerable discussion. These reactions are seen following both hip resurfacing and MoM total hip arthroplasty (THA). The phenomenon may arise owing to shedding of metal particles in high wear states, hypersensitivity with normal metal wear rates or a combination of the two., Methods: Three patients were identified who had developed a soft tissue reaction (pseudotumour) following MoM hip resurfacing procedures. The prostheses were revised to ceramic-on-ceramic (CoC) THA with only minimal debridement of the pseudotumour. Pre and postoperative magnetic resonance imaging was performed to assess the size of the lesions., Results: Progressive and satisfactory resolution of the associated pseudotumours was identified following revision of the prostheses to CoC THA., Conclusions: In the early stages of pseudotumour formation following MoM hip resurfacing, this potentially devastating condition can be managed adequately with revision to a CoC bearing THA with minimal soft tissue excision.

Objective: To investigate associations between physical activity, comorbidity severity, depressive symptoms, and health-related quality of life in type 2 diabetes mellitus., Subjects and Methods: All individuals, 200 patients and 50 controls, aged from 40 to 60 years, were investigated by interview, and all variables were measured concurrently. Physical activity was evaluated by the International Physical Activity Questionnaire (IPAQ), Health-Related Quality of Life (HRQL) by the Short-Form Health Survey (SF-36), comorbidity severity by the Charlson Comorbidity Index (CCI), and depressive symptoms by the Beck Depression Inventory (BDI-II > 16). Single and multiple regression analysis evaluated the effects of independent variables on physical activity., Results: The patients had more depressive symptoms and greater comorbidity severity (p < 0.005). Diabetic patients showed better activity levels (IPAQ) (p < 0.005). Functional Capacity, General State of Health, and Physical Limitation were the most affected subscales in the SF-36 evaluation of the HRQL. Sedentary diabetic patients had higher waist circumference, waist-to-hip ratios, more depressive symptoms, and worse HRQL. Functional capacity (p = 0.000), followed by General State of Health (p = 0.02), were the health status measure subscales independently associated with physical activity., Conclusions: The findings suggest that increasing patient independence and treating depressive symptoms can promote physical activity for type 2 diabetes mellitus patients. It is suggested that group activities and caregivers/family support might compensate for the patient dependence, and increase adherence to exercise programs in those that are less active.

Objective: To assess whether a warning system based on mobile SMS messages increases the adherence of HIV-infected Brazilian women to antiretroviral drug-based treatment regimens and their impressions and satisfaction with respect to incoming messages., Design: A randomized controlled trial was conducted from May 2009 to April 2010 with HIV-infected Brazilian women. All participants (n=21) had a monthly multidisciplinary attendance; each participant was followed over a 4-month period, when adherence measures were obtained. Participants in the intervention group (n=8) received SMS messages 30 min before their last scheduled time for a dose of medicine during the day. The messages were sent every Saturday and Sunday and on alternate days during the working week. Participants in the control group (n=13) did not receive messages., Measurements: Self-reported adherence, pill counting, microelectronic monitors (MEMS) and an interview about the impressions and satisfaction with respect to incoming messages., Results: The HIV Alert System (HIVAS) was developed over 7 months during 2008 and 2009. After the study period, self-reported adherence indicated that 11 participants (84.62%) remained compliant in the control group (adherence exceeding 95%), whereas all 8 participants in the intervention group (100.00%) remained compliant. In contrast, the counting pills method indicated that the number of compliant participants was 5 (38.46%) for the control group and 4 (50.00%) for the intervention group. Microelectronic monitoring indicated that 6 participants in the control group (46.15%) were adherent during the entire 4-month period compared to 6 participants in the intervention group (75.00%). According to the feedback of the 8 participants who completed the research in the intervention group, along with the feedback of 3 patients who received SMS for less than 4 months, that is, did not complete the study, 9 (81.81%) believed that the SMS messages aided them in treatment adherence, and 10 (90.90%) responded that they would like to continue receiving SMS messages., Conclusion: SMS messaging can help Brazilian women living with HIV/AIDS to adhere to antiretroviral therapy for a period of at least 4 months. In general, the results are encouraging because the SMS messages stimulated more participants in the intervention group to be adherent to their treatment, and the patients were satisfied with the messages received, which were seen as reminders, incentives and signs of affection by the health clinic for a marginalized population., (Copyright © 2012. Published by Elsevier Ireland Ltd.)

The replacement of defective organs with healthy ones is an old problem, but only a few years ago was this issue put into practice. Improvements in the whole transplantation process have been increasingly important in clinical practice. In this context are clinical decision support systems (CDSSs), which have reflected a significant amount of work to use mathematical and intelligent techniques. The aim of this article was to present consideration of intelligent techniques used in recent years (2009 and 2010) to analyze organ transplant databases. To this end, we performed a search of the PubMed and Institute for Scientific Information (ISI) Web of Knowledge databases to find articles published in 2009 and 2010 about intelligent techniques applied to transplantation databases. Among 69 retrieved articles, we chose according to inclusion and exclusion criteria. The main techniques were: Artificial Neural Networks (ANN), Logistic Regression (LR), Decision Trees (DT), Markov Models (MM), and Bayesian Networks (BN). Most articles used ANN. Some publications described comparisons between techniques or the use of various techniques together. The use of intelligent techniques to extract knowledge from databases of healthcare is increasingly common. Although authors preferred to use ANN, statistical techniques were equally effective for this enterprise., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The gold standard for nephrotoxicity and acute cellular rejection (ACR) is a biopsy, an invasive and expensive procedure. More efficient strategies to screen patients for biopsy are important from the clinical and financial points of view. The aim of this study was to evaluate various artificial intelligence techniques to screen for the need for a biopsy among patients suspected of nephrotoxicity or ACR during the first year after renal transplantation. We used classifiers like artificial neural networks (ANN), support vector machines (SVM), and Bayesian inference (BI) to indicate if the clinical course of the event suggestive of the need for a biopsy. Each classifier was evaluated by values of sensitivity and area under the ROC curve (AUC) for each of the classifiers. The technique that showed the best sensitivity value as an indicator for biopsy was SVM with an AUC of 0.79 and an accuracy rate of 79.86%. The results were better than those described in previous works. The accuracy for an indication of biopsy screening was efficient enough to become useful in clinical practice., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction: Internet users are increasingly using the worldwide web to search for information relating to their health. This situation makes it necessary to create specialized tools capable of supporting users in their searches., Objective: To apply and compare strategies that were developed to investigate the use of the Portuguese version of Medical Subject Headings (MeSH) for constructing an automated classifier for Brazilian Portuguese-language web-based content within or outside of the field of healthcare, focusing on the lay public., Methods: 3658 Brazilian web pages were used to train the classifier and 606 Brazilian web pages were used to validate it. The strategies proposed were constructed using content-based vector methods for text classification, such that Naive Bayes was used for the task of classifying vector patterns with characteristics obtained through the proposed strategies., Results: A strategy named InDeCS was developed specifically to adapt MeSH for the problem that was put forward. This approach achieved better accuracy for this pattern classification task (0.94 sensitivity, specificity and area under the ROC curve)., Conclusions: Because of the significant results achieved by InDeCS, this tool has been successfully applied to the Brazilian healthcare search portal known as Busca Saúde. Furthermore, it could be shown that MeSH presents important results when used for the task of classifying web-based content focusing on the lay public. It was also possible to show from this study that MeSH was able to map out mutable non-deterministic characteristics of the web., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Personal digital assistants (PDAs) are being increasingly used on the health field, however, there are not many papers guiding a PDA-software development process concerning its usability in health field. This paper presents our experience dealing with PDAs regarding some elements of usability. We have shown that if simple yet extremely important points are to be observed before and during the development process, usability on PDA software can be greatly improved.

Reasons for Performing Study: Probiotics have not been demonstrated to provide any beneficial health effects in horses, possibly because of improper selection of probiotic organisms. This study was designed to identify lactic acid bacteria of equine origin with predetermined beneficial properties which might make them useful as therapeutic probiotics., Hypothesis: A small percentage of lactic acid bacteria that are native to the intestinal tract of horses possess properties that may be useful in the treatment and/or prevention of gastrointestinal disease in horses., Methods: Faecal samples were collected from healthy mature horses and foals. Lactic acid bacteria were isolated and tested for the ability to grow in acid and bile environments, aerotolerance and in vitro inhibition of enteropathogens. One isolate that possessed these properties was administered orally to healthy mature horses and foals and gastrointestinal survival was assessed., Results: Of the 47 tested organisms, 18 were deemed to be adequately acid- and bile-tolerant. All were aerotolerant. Four organisms markedly inhibited Salmonella spp. One isolate, Lactobacillus pentosus WE7, was subjectively superior and chosen for further study. It was also inhibitory against E. coli, moderately inhibitory against S. zooepidemicus and C. difficile and mildly inhibitory against C. perfringens. After oral administration, this isolate was recovered from the faeces of 8/9 (89%) foals and 7/8 (87.5%) mature horses., Conclusions: Lactobacillus pentosus WE7 possesses in vitro and in vivo properties that may be useful for the prevention and treatment of enteric disease in horses., Potential Relevance: The beneficial in vitro and in vivo properties that L. pentosus WE7 possesses indicate that randomised, blinded, placebo-controlled efficacy studies are warranted.