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Skin wound healing is coordinated by a delicate balance between proinflammatory and anti-inflammatory responses, which can be affected by opportunistic pathogens and metabolic or vascular diseases. Several antimicrobial peptides (AMPs) possess immunomodulatory properties, suggesting their potential to support skin wound healing. Here, we evaluated the proregenerative activity of three recently described AMPs (Clavanin A, Clavanin-MO, and Mastoparan-MO). Human primary dermal fibroblasts (hFibs) were used to determine peptide toxicity and their capacity to induce cell proliferation and migration. Furthermore, mRNA analysis was used to investigate the modulation of genes associated with skin regeneration. Subsequently, the regenerative potential of the peptides was further confirmed using an ex vivo organotypic model of human skin (hOSEC)-based lesion. Our results indicate that the three molecules evaluated in this study have regenerative potential at nontoxic doses (i.e., 200 µM for Clavanin-A and Clavanin-MO, and 6.25 µM for Mastoparan-MO). At these concentrations, all peptides promoted the proliferation and migration of hFibs during in vitro assays. Such processes were accompanied by gene expression signatures related to skin regenerative processes, including significantly higher KI67, HAS2 and CXCR4 mRNA levels induced by Clavanin A and Mastoparan-MO. Such findings translated into significantly accelerated wound healing promoted by both Clavanin A and Mastoparan-MO in hOSEC-based lesions. Overall, the data demonstrate the proregenerative properties of these peptides using human experimental skin models, with Mastoparan-MO and Clavanin A showing much greater potential for inducing wound healing compared to Clavanin-MO.

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Introduction: The identification of chemical compounds that interfere with SARS-CoV-2 replication continues to be a priority in several academic and pharmaceutical laboratories. Computational tools and approaches have the power to integrate, process and analyze multiple data in a short time. However, these initiatives may yield unrealistic results if the applied models are not inferred from reliable data and the resulting predictions are not confirmed by experimental evidence. Methods: We undertook a drug discovery campaign against the essential major protease (MPro) from SARS-CoV-2, which relied on an in silico search strategy -performed in a large and diverse chemolibrary- complemented by experimental validation. The computational method comprises a recently reported ligand-based approach developed upon refinement/learning cycles, and structure-based approximations. Search models were applied to both retrospective (in silico) and prospective (experimentally confirmed) screening. Results: The first generation of ligand-based models were fed by data, which to a great extent, had not been published in peer-reviewed articles. The first screening campaign performed with 188 compounds (46 in silico hits and 100 analogues, and 40 unrelated compounds: flavonols and pyrazoles) yielded three hits against MPro (IC50 ≤ 25 µM): two analogues of in silico hits (one glycoside and one benzo-thiazol) and one flavonol. A second generation of ligand-based models was developed based on this negative information and newly published peer-reviewed data for MPro inhibitors. This led to 43 new hit candidates belonging to different chemical families. From 45 compounds (28 in silico hits and 17 related analogues) tested in the second screening campaign, eight inhibited MPro with IC50 = 0.12-20 µM and five of them also impaired the proliferation of SARS-CoV-2 in Vero cells (EC50 7-45 µM). Discussion: Our study provides an example of a virtuous loop between computational and experimental approaches applied to target-focused drug discovery against a major and global pathogen, reaffirming the well-known "garbage in, garbage out" machine learning principle.

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In skin lesions, the development of microbial infection affects the healing process, increasing morbidity and mortality rates in patients with severe burns, diabetic foot, and other types of skin injuries. Synoeca-MP is an antimicrobial peptide (AMP) that exhibits activity against several bacteria of clinical importance, but its cytotoxicity can represent a problem for its positioning as an effective antimicrobial compound. In contrast, the immunomodulatory peptide IDR-1018 presents low toxicity and a wide regenerative potential due to its ability to reduce apoptotic mRNA expression and promote skin cell proliferation. In the present study, we used human skin cells and a 3D skin equivalent models to analyze the potential of the IDR-1018 peptide to attenuate the cytotoxicity of synoeca-MP, as well as the influence of synoeca-MP/IDR-1018 combination on cell proliferation, regenerative processes, and wound repair. We found that the addition of IDR-1018 significantly improved the biological properties of synoeca-MP on skin cells without modifying its antibacterial activity against S. aureus. Likewise, in both melanocytes and keratinocytes, the treatment with synoeca-MP/IDR-1018 combination induces cell proliferation and migration, while in a 3D human skin equivalent model, it can accelerate wound reepithelization. Furthermore, treatment with this peptide combination generates an up-regulation in the expression of pro-regenerative genes in both monolayer cell cultures and in 3D skin equivalents. This data suggests that the synoeca-MP/IDR-1018 combination possesses a good profile of antimicrobial and pro-regenerative activity, opening the door to the development of new strategies for the treatment of skin lesions.

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The invasive nature of Toxoplasma gondii is closely related to the properties of its cytoskeleton, which is constituted by a group of diverse structural and dynamic components that play key roles during the infection. Even if there have been numerous reports about the composition and function of the Toxoplasma cytoskeleton, the ultrastructural organization of some of these components has not yet been fully characterized. This study used a detergent extraction process and several electron microscopy contrast methods that allowed the successful isolation of the cytoskeleton of Toxoplasma tachyzoites. This process allowed for the conservation of the structures known to date and several new structures that had not been characterized at the ultrastructural level. For the first time, characterization was achieved for a group of nanofibers that allow the association between the polar apical ring and the conoid as well as the ultrastructural characterization of the apical cap of the parasite. The ultrastructure and precise location of the peripheral rings were also found, and the annular components of the basal complex were characterized. Finally, through immunoelectron microscopy, the exact spatial location of the subpellicular network inside the internal membrane system that forms the pellicle was found. The findings regarding these new structures contribute to the knowledge concerning the biology of the Toxoplasma gondii cytoskeleton. They also provide new opportunities in the search for therapeutic strategies aimed at these components with the purpose of inhibiting invasion and thus parasitism.

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Glyphosate [N-(phosphonomethyl)glycine] is the active ingredient in widely used broad-spectrum herbicides. Even though the toxicity mechanism of this herbicide in vertebrates is poorly understood, evidence suggests that glyphosate is an endocrine disruptor capable of producing morphological anomalies as well as cardiotoxic and neurotoxic effects. We used the zebrafish model to assess the effects of early life glyphosate exposure on the development of cartilage and bone tissues and organismal responses. We found functional alterations, including a reduction in the cardiac rate, significant changes in the spontaneous tail movement pattern, and defects in craniofacial development. These effects were concomitant with alterations in the level of the estrogen receptor alpha osteopontin and bone sialoprotein. We also found that embryos exposed to glyphosate presented spine deformities as adults. These developmental alterations are likely induced by changes in protein levels related to bone and cartilage formation.

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The Excretory/Secretory (ES) proteins of parasites are involved in invasion and colonization of their hosts. In addition, since ES proteins circulate in the extracellular space, they can be more accessible to drugs than other proteins, which makes ES proteins optimal targets for the development of new and better pharmacological strategies. Monogeneans are a group of parasitic Platyhelminthes that includes some pathogenic species problematic for finfish aquaculture. In the present study, 8297 putative ES proteins from four monogenean species which genomic resources are publicly available were identified and functionally annotated by bioinformatic tools. Additionally, for comparative purposes, ES proteins in other parasitic and free-living platyhelminths were identified. Based on data from the monogenean Gyrodactylus salaris, 15 ES proteins are considered potential drug targets. One of them showed homology to 10 cathepsins with known 3D structure. A docking molecular analysis uncovered that the anthelmintic emodepside shows good affinity to these cathepsins suggesting that emodepside can be experimentally tested as a monogenean's cathepsin inhibitor.

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The Mapocho River's upper basin (Chilean Central Andes) was studied as a proxy of a high-mountainous hydrothermally-altered (HMHA) system comprised by three sub-basins developed over very different rocks and submitted to different anthropic pressure: 1) a natural acid rock drainage (i.e., Yerba Loca), 2) a creek with mining activity in its headwaters and hydrochemically classified as non-affected by acid mine drainage (i.e., San Francisco), and 3) a low metal concentration creek (i.e., Molina). In general terms, the geochemical composition of the clastic sediments was consistent with the geochemistry inferred from the mineralogical study. However, sediments with a smaller grain size showed higher concentrations than the bigger grain size counterparts for elements such as Fe, S, Cu and As. This behavior was particularly evident in the Yerba Loca basin and it was attributed to the seasonal appearance of Fe- and Al-rich precipitates as constituents of the finer sediments. Different methodologies for the calculation of geochemical backgrounds (Tukey's inner fence, TIF; Median + 2*Median Absolute Deviation, MAD; and 95th percentile) were tested. Results suggest that the 95th percentile-method was the most appropriate for this type of mountainous systems. Using the selected methodology, three different geochemical backgrounds were calculated: 1) Yerba Loca basin, 2) Molina basin, and 3) Mapocho Upper basin. When the generated background levels were compared with the Consensus-Based (CB) Sediment Quality Guidelines; Fe, Mn, Zn, Pb, Cu, Cr, Ni and As showed background values that were consistently higher than the values set by the CB Threshold Effect Concentration and, even higher than the CB Probable Effect Concentration for Fe (MUBBackground: 6.78 wt% vs CB PEC: 4.00 wt%; and Cu (MUBBacground: 3387 mg kg-1 vs CB PEC: 149 mg kg-1). The present study clearly states the paramount importance of having a solid geochemical background before any attempt of a sediment risk assessment is made at HMHA regions.

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Glyphosate, the most commonly used pesticide worldwide, blocks aromatic amino acid biosynthetic pathways and inhibits growth in plants. Although the specific mode of action of glyphosate in animals remains unclear, adverse effects during embryonic development have been reported, including epiboly delays, morphological alterations, and changes in central nervous system development and cardiogenesis. In this study, we suggest a possible toxicity mechanism for this herbicide related to changes in microtubule stability, which could alter the distribution and dynamics of cytoskeleton components. Using zebrafish embryos to evaluate in vivo effects of glyphosate exposure (5, 10, and 50 µg/ml), we found significant reductions in the levels of acetylated α-tubulin (50 µg/ml) and in the polymeric tubulin percentage in zebrafish embryos that had been exposed to 10 and 50 µg/ml glyphosate, without any changes in either the expression patterns of α-tubulin or the stability of actin filaments. These results indicate that high concentrations of glyphosate were associated with reduced levels of acetylated α-tubulin and altered microtubule stability, which may explain some of the neurotoxic and cardiotoxic effects that have been attributed to this herbicide.

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OBJECTIVE: To analyze the association between newborn and maternal characteristics and the risk for cesarean section (CS) due to cephalopelvic disproportion (CPD) and non-CPD causes compared to vaginal deliveries (VD) in a sample of infants and mothers from Merida, Yucatan, Mexico. METHODS: The final sample consisted of 3453 single, live, and term infants born between January 2016 and May 2017 at the Maternal-Infant Hospital in Merida and their mothers (aged ≥19 years). The mode of delivery was established as the dependent variables: (a) VD, (b) CS due to CPD, and (c) non-CPD CS. Independent variables were maternal height and weight, the number of previous VD, newborn weight, and neonatal birthweight (BW) index/maternal height index. A multinomial regression model was used to analyze the association between newborn and maternal characteristics and outcome variable. RESULTS: By mode of delivery, 2124 (62%) births corresponded to VD, 1042 (30%) to non-CPDCS, and 287 (8%) to CS due to CPD. Mothers who had CS due to CPD weighed more at the end of their pregnancy and were shorter. Maternal age and weight increased the risk for having CS due to CPD compared to VD and maternal height, and the number of previous VD reduces the risk for experiencing CS due to CPD compared to vaginal births. The relative risk ratio for higher neonatal BW/maternal height index was significant for CS due to CPD and non-CPD CS. CONCLUSION: According to our results from a public hospital in Merida, Mexico, CPD is a result of the interrelation of maternal and fetal size, rather than an independent result of maternal height or BW.

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An integral bioprocess to produce lactic acid (LA) from banana peel (BP) was studied. Oxidases produced by Trametes versicolor and hydrolases produced by Aspergillus flavipes and Aspergillus niger saccharified BP at optimal conditions: 230 rpm, 66 g/L BP, and 73.5% (v/v) of enzymatic crude extract (using equal quantities of the enzymatic extracts). At bioreactor scale (1 L), the joint action of oxidases and hydrolases released 18 g/L of reducing sugars (RS) after 24 h (60% corresponded to glucose), consuming the BP polysaccharides. Lactobacillus delbrueckii fermented the released RS, producing 10 g/L of LA; while in the sequential fermentation (inoculating L. delbrueckii after saccharification), 28 g/L of LA were produced, observing an apparent decrease in feedback inhibition of hydrolases below 1.5 g/L of RS. This process is susceptible for upscaling to produce high LA concentrations and represents a platform to utilize agroindustrial wastes to obtain value-added products.

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Cytokinin forchlorfenuron (FCF), a synthetic cytokinin, has been used specifically for the characterization of septins. In spite of genomic evidence of their existence, nothing is known about septin filaments in taeniid cestodes. The aim of this work was to determine the presence of a septin-like protein in cysticerci of Taenia crassiceps and Taenia solium using the deduced amino acid sequence of T. solium septin 4 (SEPT4_Tsm), to design and synthesize a derived immunogenic peptide (residues 88 to 103), to prepare a specific rabbit polyclonal antibody, and to examine the effects of FCF at different concentrations and exposure times on an in vitro culture of T. crassiceps cysticerci. In vitro, FCF altered the morphology and motility of T. crassiceps cysticerci, and its effects were reversible under specific concentrations. In addition, we observed by ultrastructural observation that FCF alters the cellular subunit of the protonephridial system of cestodes, where disruption of the axoneme pattern of flame cells was observed. The rabbit polyclonal antibody prepared against the synthetic peptide recognized a major band of 41 kDa in both parasites. Our results establish the importance of SEPT4_Tsm in the dynamics and survival of taeniid cysticerci, as well as their susceptibility to FCF. This is also the first report that a septin is present in the cytoskeleton of taeniids.

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After host cell invasion, Toxoplasma secretes a variety of dense granule proteins (GRA proteins) from its secretory dense granules, which are involved in the biogenesis of the parasitophorous vacuole (PV). TgGRA8I is predicted to contain proline-rich domains, which are structural features of some cytoskeleton-related proteins. In agreement with this observation, previous proteomic analyses revealed the presence of TgGRA8I in the Toxoplasma sub-pellicular cytoskeleton. In the present study, we show (1) by docking analyses that TgGRA8I may interact with both Toxoplasma ß-tubulin and actin; (2) by immunoelectron microscopy, proteomic, biochemical, and cellular approaches that TgGRA8I associates with sub-pellicular microtubules and actin at the parasite sub-pellicular cytoskeleton; (3) that type I parasites (RH strain) lacking the GRA8 gene (RHΔku80Δgra8) exhibit loss of conoid extrusion, diminished cell infection, and egress capabilities, and that these motility impairments were likely due to important alterations in their sub-pellicular cytoskeleton, in particular their sub-pellicular microtubules and meshwork. Parasites lacking the GRA4 gene (RHΔku80Δgra4) did not show modifications in the organization of the sub-pellicular cytoskeleton. Collectively, these results demonstrated that TgGRA8I is a dense granule protein that, besides its role in the formation of the PV, contributes to the organization of the parasite sub-pellicular cytoskeleton and motility. This is the first proline-rich protein described in the Toxoplasma cytoskeleton, which is a key organelle for both the parasite motility and the invasion process. Knowledge about the function of cytoskeleton components in Toxoplasma is fundamental to understand the motility process and the host cell invasion mechanism. Refining this knowledge should lead to the design of novel pharmacological strategies for the treatment against toxoplasmosis.

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In type 2 diabetes mellitus there is an overproduction of chylomicron in the postprandial state that is associated with increased cardiovascular risk. Current evidence points out a leading role of enterocyte in dyslipidemia of type 2 diabetes mellitus, since it increases the production of apolipoprotein B-48 in response to a raise in plasma free fatty acids and glucose. The chylomicron metabolism is regulated by many factors apart from ingested fat, including hormonal and metabolic elements. More recently, studies about the role of gut hormones, have demonstrated that glucagon-like peptide-1 decreases the production of apolipoprotein B-48 and glucagon-like peptide-2 enhances it. Insulin acutely inhibits intestinal chylomicron production in healthy humans, whereas this acute inhibitory effect on apolipoprotein B-48 production is blunted in type 2 diabetes mellitus. Understanding these emerging regulators of intestinal chylomicron secretion may offer new mechanisms of control for its metabolism and provide novel therapeutic strategies focalized in type 2 diabetes mellitus postprandial hyperlipidemia with the reduction of cardiovascular disease risk.

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En la diabetes mellitus tipo 2 el aumento en la producción de quilomicrón en el estado post-prandial se asocia a mayor riesgo cardiovascular. La evidencia actual posiciona al enterocito como actor principal en la dislipemia de la diabetes mellitus tipo 2 debido a que aumenta la producción de apolipoproteína B-48 en respuesta a una elevación de ácidos grasos libres y glucosa. El metabolismo del quilomicrón se encuentra regulado por múltiples factores independientes además de la ingesta de grasa alimentaria. Entre estos factores se destacan las hormonas intestinales, como el péptido similar al glucagón tipo 1 que disminuye la producción de apolipoproteína B-48 y el péptido similar al glucagón tipo 2 que la aumenta. Por otro lado, la insulina inhibe de forma aguda la producción de quilomicrón en el sujeto sano mientras que en la diabetes mellitus tipo 2, este efecto está ausente. La comprensión de los factores reguladores emergentes de la secreción de quilomicrón permite vislumbrar nuevos mecanismos de control en su metabolismo y aportar estrategias terapéuticas focalizadas en la hiperlipidemia posprandial en la diabetes mellitus tipo 2 con la reducción del riesgo cardiovascular.

In type 2 diabetes mellitus there is an overproduction of chylomicron in the postprandial state that is associated with increased cardiovascular risk. Current evidence points out a leading role of enterocyte in dyslipidemia of type 2 diabetes mellitus, since it increases the production of apolipoprotein B-48 in response to a raise in plasma free fatty acids and glucose. The chylomicron metabolism is regulated by many factors apart from ingested fat, including hormonal and metabolic elements. More recently, studies about the role of gut hormones, have demonstrated that glucagon-like peptide-1 decreases the production of apolipoprotein B-48 and glucagon-like peptide-2 enhances it. Insulin acutely inhibits intestinal chylomicron production in healthy humans, whereas this acute inhibitory effect on apolipoprotein B-48 production is blunted in type 2 diabetes mellitus. Understanding these emerging regulators of intestinal chylomicron secretion may offer new mechanisms of control for its metabolism and provide novel therapeutic strategies focalized in type 2 diabetes mellitus postprandial hyperlipidemia with the reduction of cardiovascular disease risk.

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INTRODUCTION: Using the best current evidence to inform clinical decisions remains a challenge for clinicians. Given the scarcity of trustworthy clinical practice guidelines providing recommendations to answer clinicians' daily questions, clinical decision support systems (ie, assistance in question identification and answering) emerge as an attractive alternative. The trustworthiness of the recommendations achieved by such systems is unknown. OBJECTIVE: To evaluate the trustworthiness of a question identification and answering system that delivers timely recommendations. DESIGN: Cross-sectional study. METHODS: We compared the responses to 100 clinical questions related to inpatient management provided by two rapid response methods with 'Gold Standard' recommendations. One of the rapid methods was based on PubMed and the other on Epistemonikos database. We defined our 'Gold Standard' as trustworthy published evidence-based recommendations or, when unavailable, recommendations developed locally by a panel of six clinicians following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Recommendations provided by the rapid strategies were classified as potentially misleading or reasonable. We also determined if the potentially misleading recommendations could have been avoided with the appropriate implementation of searching and evidence summary tools. RESULTS: We were able to answer all of the 100 questions with both rapid methods. Of the 200 recommendations obtained, 6.5% (95% CI 3% to 9.9%) were classified as potentially misleading and 93.5% (95% CI 90% to 96.9%) as reasonable. 6 of the 13 potentially misleading recommendations could have been avoided by the appropriate usage of the Epistemonikos matrix tool or by constructing summary of findings tables. No significant differences were observed between the evaluated rapid response methods. CONCLUSION: A question answering service based on the GRADE approach proved feasible to implement and provided appropriate guidance for most identified questions. Our approach could help stakeholders in charge of managing resources and defining policies for patient care to improve evidence-based decision-making in an efficient and feasible manner.

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Se presenta el caso de un lactante de 24 meses de edad diagnosticado de púrpura trombopénica corticodependiente, en el que se confirmó infección activa por citomegalovirus mediante serología y aislamiento del virus en orina. Ante la mala evolución de la enfermedad y sospechando relación causal con el virus, se inició valganciclovir vía oral hasta un total de 5 meses, obteniendo excelente respuesta con resolución simultánea de ambos procesos y sin efectos secundarios reseñables.

We report a case of a 24 months old child, diagnosed with corticodependent thrombocytopenia in which active cytomegalovirus infection was confirmed sustituir resaltado por: by means of serology and viris isolation in urine.. Due to the patient's worsening, we suspected a link between both processes and started oral valganciclovir, given for a total of 5 months. We documented excellent simultaneous response in both pathologies, and without relevant side effects.

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PURPOSE: Clinical data on patients with intra-abdominal candidiasis (IAC) is still scarce. METHODS: We collected data from 13 hospitals in Italy, Spain, Brazil, and Greece over a 3-year period (2011-2013) including patients from ICU, medical, and surgical wards. RESULTS: A total of 481 patients were included in the study. Of these, 27% were hospitalized in ICU. Mean age was 63 years and 57% of patients were male. IAC mainly consisted of secondary peritonitis (41%) and abdominal abscesses (30%); 68 (14%) cases were also candidemic and 331 (69%) had concomitant bacterial infections. The most commonly isolated Candida species were C. albicans (n = 308 isolates, 64%) and C. glabrata (n = 76, 16%). Antifungal treatment included echinocandins (64%), azoles (32%), and amphotericin B (4%). Septic shock was documented in 40.5% of patients. Overall 30-day hospital mortality was 27% with 38.9% mortality in ICU. Multivariate logistic regression showed that age (OR 1.05, 95% CI 1.03-1.07, P < 0.001), increments in 1-point APACHE II scores (OR 1.05, 95% CI 1.01-1.08, P = 0.028), secondary peritonitis (OR 1.72, 95% CI 1.02-2.89, P = 0.019), septic shock (OR 3.29, 95% CI 1.88-5.86, P < 0.001), and absence of adequate abdominal source control (OR 3.35, 95% CI 2.01-5.63, P < 0.001) were associated with mortality. In patients with septic shock, absence of source control correlated with mortality rates above 60% irrespective of administration of an adequate antifungal therapy. CONCLUSIONS: Low percentages of concomitant candidemia and high mortality rates are documented in IAC. In patients presenting with septic shock, source control is fundamental.

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En la Leucemia linfática aguda (LLA) pediátrica las cinco fusiones génicas más frecuentes descritas son: ETV6/RUNX1, BCR/ABL variante p190, BCR/ABL variante p210, E2A/PBX1, MLL/AF4 y representan alrededor del 40%. Se busca determinar la frecuencia e importancia de las principales fusiones génica en la leucemia linfática en un grupo de pacientes pediátricos del INEN. Se realizó el análisis molecular de cinco genes de fusión en 23 pacientes con diagnóstico de LLA-B, obteniéndose las siguientes frecuencias: ETV6/RUNX1 (17.4%), BCR/ABL variante p190 (8.7%), BCR/ABL variante p210 (8.7%), E2A/PBX1 (8.7%), MLL/AF4 (4.3%). Esta metodología de estudio de los cinco genes de fusión, debe considerarse como herramienta de apoyo al diagnóstico y monitoreo en uso de terapias blanco en todos los casos de la LLA-B pediátricas.

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INTRODUCTION: There is limited high-quality evidence regarding the usefulness of bibliographic assistance in improving clinically important outcomes in hospitalised patients. This study was designed to evaluate the impact of providing attending physicians with bibliographic information to assist them in answering medical questions that arise during daily clinical practice. METHODS: All patients admitted to the Internal Medicine ward of Hospital Aleman in Buenos Aires between March and August 2010 were randomly assigned to one of two groups: intervention or control. Throughout this period, the medical questions that arose during morning rounds were identified. Bibliographic research was conducted to answer only those questions that emerged during the discussion of patients assigned to the intervention group. The compiled information was sent via e-mail to all members of the medical team. RESULTS: 809 patients were included in the study, 407 were randomly assigned to a search-supported group and 402 to a control group. There was no significant difference in death or transfer to an intensive care unit (ICU) (RR 1.09 (95% CI 0.7 to 1.6)), rehospitalisation (RR 1.0 (95% CI 0.7 to 1.3)) or length of hospitalisation (6.5 vs 6.0 days, p=0.25). The subgroup of search-supported physicians' patients (n=31), whose attending physicians received hand-delivered information, had a significantly lower risk of death or transfer to an ICU compared with the control group (0% vs 13.7%, p=0.03). CONCLUSIONS: The impact of bibliographic assistance on clinically important outcomes could not be proven by this study. However, results suggest that some interventions, such as delivering information by hand, might be beneficial in a subgroup of inpatients.

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OBJECTIVE: We present the case of a patient who sustained a gunshot wound; the projectile was located in the knee and was arthroscopically removed. CLINICAL CASE: A 31 year-old patient sustained a gunshot wound in the right thigh, right hand and left knee. X-rays revealed the presence of a projectile in the knee, thigh and hand. The projectile was arthroscopically removed. DISCUSSION: Traumas causing articular wounds of the knee are infrequent. Excluding the most frequent causes of articular wounds, a small percentage of them are due to gunshot wounds. There is consensus around arthroscopy as a technique useful to remove articular foreign bodies; it has advantages over open surgery. This procedure minimizes surgical morbidity, reduces the risk of septic arthritis, synovitis, arthropathy or systemic lead toxicity, and it also hastens the patient's functional recovery. Knee arthroscopy allows physicians to provide a definitive treatment of these injuries, explore the joint, diagnose associated injuries and perform debridement and articular lavage. CONCLUSION: Arthroscopy is an effective tool for the extraction of articular projectiles; it also allows diagnosing and treating associated lesions.

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