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Inflammation plays a significant role in lung infection including that caused by Mycobacterium tuberculosis (M.tb), where both adaptive and innate lymphocytes can affect infection control. How inflammation affects infection is understood in a broad sense, including inflammaging (chronic inflammation) seen in the elderly, but the explicit role that inflammation can play in regulation of lymphocyte function is not known. To fill this knowledge gap, we used an acute lipopolysaccharide (LPS) treatment in young mice and studied lymphocyte responses, focusing on CD8 T cell subsets. LPS treatment decreased the total numbers of T cells in the lungs of LPS mice, while also increasing the number of activated T cells. We demonstrate that lung CD8 T cells from LPS mice became capable of an antigen independent innate-like IFN-γ secretion, dependent on IL-12p70 stimulation, paralleling innate-like IFN-γ secretion of lung CD8 T cells from old mice. Overall, this study provides information on how acute inflammation can affect lymphocytes, particularly CD8 T cells, which could potentially affect immune control of various disease states.

While there is an increasing awareness regarding the culture of humanization, which is strongly needed in the healthcare environment, little knowledge has been provided in relation to accurate strategies to teach humanization skills to healthcare undergraduate students, as well as to healthcare professionals. Furthermore, the usefulness of new technologies to improve humanization skills has hardly been addressed so far in the scientific literature, including promising strategies such as Metaverse-related technologies. Presumably, this is the first systematic review focused on the efficacy of Metaverse-related technologies to increase the acquisition of humanization skills in the healthcare environment. The purpose of this study was to review the scientific studies published in the last decade to answer the following two questions: (1) are Metaverse-related technologies useful in enhancing humanization skills in the healthcare environment? (2) What are the advantages and disadvantages that should be addressed to successfully develop Metaverse-related technologies in the healthcare sector? We conducted a systematic review of the peer-reviewed literature from EBSCO, Ovid, PubMed, Scopus, and Web of Science (WOS), following the PRISMA statements and using the following keywords: “humanization + Metaverse”; “humanization + mixed reality”; “humanization + extended reality”; “humanization + augmented reality”; “humanization + virtual reality”; “humanization + app”; “humanization + telemedicine”; “humanization + digital health”; “humanization + eHealth”; “humanization + telehealth”; “humanization + web-based”; “humanization + website”; “humanization + digital”; “humanization + online”; and “humanization + internet”. Studies published from 2012 to the present, written in the English language, were reviewed. A total of 505 records were obtained, of which three were selected based on the inclusion and exclusion criteria. The results will be helpful in developing new strategies to improve humanization skills in the health sphere.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), emerged in December 2019 in Wuhan, China, and rapidly spread throughout the world, threatening global public health. An animal model is a valuable and a crucial tool that allows understanding of nature in the pathogenesis of SARS-CoV-2 and its associated COVID-19 disease. Here we introduce detailed protocols of SARS-CoV-2 infection and COVID-19 disease using C57BL/6 (B6) transgenic mice expressing the human angiotensin-converting enzyme 2 (hACE2) from the human cytokeratin 18 promoter (K18 hACE2). To mimic natural SARS-CoV-2 infection, K18 hACE2 transgenic mice are infected intranasally under anesthesia. Upon infection, viral pathogenesis is determined by monitoring changes in body weight (morbidity) and monitoring survival (mortality), cytokine/chemokine responses, gross-lung pathology, histopathology, and viral replication in tissues. The presence of the virus and viral replication is evaluated by immunohistochemistry (IHC) and viral titrations, respectively, from the upper (nasal turbinate) and the lower (lungs) respiratory tracts, and nervous system (brain). Also, the immune response to SARS-CoV-2 infection is measured by cytokine/chemokine enzyme-linked immunosorbent assay (ELISA) from lung, spleen and brain homogenates to characterize the cytokine storm that hallmarks as one of the major causes of death caused by SARS-CoV-2 infection. This small rodent animal model based on the use of K18 hACE2 transgenic mice represents an excellent option to understand the pathogenicity of natural SARS-CoV-2 strains and its recently described Variants of Concern (VoC), and will be applicable to the identification and characterization of prophylactic (vaccine) and therapeutic (antiviral and/or neutralizing monoclonal antibodies) strategies for the prevention or treatment of SARS-CoV-2 infection or its associated COVID-19 disease.

The landscape of Extended Reality (ER), which includes Virtual Reality (VR), Augmented Reality (AR), and Mixed Reality (MR) is rapidly changing. However, despite the promising results from many randomized controlled trials (RCTs) developed on healthcare environments, there is a lack of standardization, specifically to determine their effectiveness in academic settings. To our best knowledge, this is the first systematic review addressing the efficacy of MR to enhance learning and skills acquisition in undergraduate mental health education. The purposes of this study were to review the scientific literature of those studies involving MR and undergraduate mental health education, to answer the two following questions: (1) Is MR useful to enhance the acquisition of knowledge and skill training in undergraduate mental health education, and (2) Which are the advantages and disadvantages that should be addressed to successfully develop MR in undergraduate mental health education? We conducted a systematic review of the peer-reviewed literature from EBSCO, Ovid, PubMed, and Scopus y WOS (Web of Science), following the PRISMA statements and using “mixed reality + education”, “mixed reality + student”, “mixed reality + undergraduate”, and “mixed reality + mental health”, as keywords. Those studies published between 2012 to present, in English or Spanish language, were reviewed. A total of 2608 records were retrieved, and only 6 publications met the inclusion criteria, and were finally included. MR training used was varied. There were no studies providing specific outcomes regarding the student’s acquired knowledge (theoretical concepts) after using MR. Several strengths and weaknesses of using MR with students were discussed. The results will be useful to develop innovative MR strategies to improve undergraduate mental health education, due to the lack of studies focused on this topic.

Inflammation plays a crucial role in the control of Mycobacterium tuberculosis infection. In this study, we demonstrate that an inflammatory pulmonary environment at the time of infection mediated by lipopolysaccharide treatment in mice confers enhanced protection against M. tuberculosis for up to 6 months postinfection. This early and transient inflammatory environment was associated with a neutrophil and CD11b+ cell influx and increased inflammatory cytokines. In vitro infection demonstrated that neutrophils from lipopolysaccharide-treated mice exhibited increased association with M. tuberculosis and had a greater innate capacity for killing M. tuberculosis. Finally, partial depletion of neutrophils in lipopolysaccharide-treated mice showed an increase in M. tuberculosis burden, suggesting neutrophils played a part in the protection observed in lipopolysaccharide-treated mice. These results indicate a positive role for an inflammatory environment in the initial stages of M. tuberculosis infection and suggest that acute inflammation at the time of M. tuberculosis infection can positively alter disease outcome. IMPORTANCE Mycobacterium tuberculosis, the causative agent of tuberculosis disease, is estimated to infect one-fourth of the world’s population and is one of the leading causes of death due to an infectious disease worldwide. The high-level variability in tuberculosis disease responses in the human populace may be linked to immune processes related to inflammation. In many cases, inflammation appears to exasperate tuberculosis responses; however, some evidence suggests inflammatory processes improve control of M. tuberculosis infection. Here, we show an acute inflammatory stimulus in mice provides protection against M. tuberculosis for up to 6 months, suggesting acute inflammation can positively affect M. tuberculosis infection outcome.

New antibiotics are needed to combat rising levels of resistance, with new Mycobacterium tuberculosis (Mtb) drugs having the highest priority. However, conventional whole-cell and biochemical antibiotic screens have failed. Here we develop a strategy termed PROSPECT (primary screening of strains to prioritize expanded chemistry and targets), in which we screen compounds against pools of strains depleted of essential bacterial targets. We engineered strains that target 474 essential Mtb genes and screened pools of 100–150 strains against activity-enriched and unbiased compound libraries, probing more than 8.5 million chemical–genetic interactions. Primary screens identified over tenfold more hits than screening wild-type Mtb alone, with chemical–genetic interactions providing immediate, direct target insights. We identified over 40 compounds that target DNA gyrase, the cell wall, tryptophan, folate biosynthesis and RNA polymerase, as well as inhibitors that target EfpA. Chemical optimization yielded EfpA inhibitors with potent wild-type activity, thus demonstrating the ability of PROSPECT to yield inhibitors against targets that would have eluded conventional drug discovery. A high-throughput chemical–genetic screening approach for the discovery of targets and chemicals to treat Mycobacterium tuberculosis yields tenfold more hit compounds than conventional whole-cell screening methods.

Inflammation plays a crucial role in the control of Mycobacterium tuberculosis (M.tb) infection. In this study, we demonstrate that an inflammatory pulmonary environment at the time of infection mediated by liposaccharide (LPS) treatment in mice confers enhanced protection against M.tb for up to 6 months post infection. This transient protective inflammatory environment was associated with a neutrophil and monocyte/macrophage influx as well as increased inflammatory cytokines. In vitro infection of neutrophils from LPS treated mice demonstrated that LPS neutrophils exhibited increased recognition of M.tb, and had a greater innate capacity for killing M.tb. Finally, partial depletion of neutrophils in LPS treated mice showed an increase in M.tb burden, suggesting neutrophils conferred the enhanced protection observed in LPS treated mice. These results indicate a positive role of an inflammatory environment during initial M.tb infection, and suggests that acute inflammation at the time of M.tb infection can positively alter disease outcome.

Peripheral nerve injuries are among the most complex conditions facing upper-extremity surgeons. Loss of wrist extension can result in marked limitations, including loss of pinch and grip strength with discoordination of grasp and release. Tendon transfers represent the mainstay of operative treatment and have proven to be an effective method for restoring loss of wrist extension. The literature describes myriad techniques to restore loss of wrist extension. The best choice of transfers is dependent on what is available, depending on the level of injury. The present article describes a novel technique of transferring 2 flexor digitorum superficialis (FDS) tendons for wrist extension for patients with radial nerve lesions. The technique involves direct transfer of the long and ring finger FDS tendons to the third metacarpal bone. One FDS is routed through the interosseous membrane while the second FDS tendon is routed radially around the wrist to prevent a net supination or pronation force. If needed, the tendons can be alternatively routed to augment either pronation or supination. Passing both FDS tendons through the interosseous membrane creates a supination moment of the forearm, whereas routing both around the radius adds pronation. This article will review the relevant anatomy, indications, contraindications, operative technique, postoperative management, and outcomes.The present article describes the technique of transferring 2 FDS tendons to restore wrist extension in patients who have lost wrist extension secondary to nerve lesions, such as radial nerve palsy and brachial plexus injuries. This technique involves the transfer of the long and ring finger FDS tendons around the base of the long metacarpal. One FDS tendon is routed through the interosseous membrane, and the second FDS tendon is routed radially around the wrist to add a pronation moment to the transfer.Alternatives include nerve transfers and tendon transfersThe pronator teres tendon has been the primary donor described to restore wrist extension. However, this tendon is often inadequate and requires a periosteal extension. In addition, the pronator muscle may be involved in brachial plexus injures and unavailable as a donor. Lastly, the FDS is synergistic with wrist extension, which facilitates rehabilitation.Child and adult patients are expected to have good control of function at 3 months postoperatively, with a full recovery at 6 months postoperatively. Because the FDS is synergistic with wrist extension, rehabilitation is straightforward. The wrist is immobilized in a sugar-tong for 3 to 4 weeks postoperatively, followed by the use of a removable thermoplastic wrist brace for 4 weeks full-time, except when bathing and performing physical therapy, and then for 4 weeks at night only. Physical therapy should focus on activation and training of the FDS under therapist supervision. Supervised active extension exercises can be initiated after week 4 postoperatively, taking care to avoid wrist flexion beyond neutral and resistive exercises. Functional exercises can be initiated at 6 weeks postoperatively, with light resistance only until week 12, coinciding with the discontinued use of the wrist brace.Surgery is performed through 4 primary incisions:○ a volar oblique incision in the distal palmar crease at the base of the long and ring fingers,○ a volar transverse incision at the mid-forearm,○ a dorsal transverse incision over the midshaft of the third metacarpal,○ a dorsal forearm transverse incision opposite to the volar forearm incision to shuttle the FDS tendon.The FDS donor tendons to the long and ring fingers are isolated first.Any adhesions between the FDS and flexor digitorum profundus are divided.The FDS tendons are left in the wounds until later to prevent desiccation.On occasion, the FDS tendons can become caught in the carpal canal during harvesting and will need to be pulled back into the distal palmar incision for further lysis of connections between the FDS and flexor digitorum profundus tendons.A wide window, not a slit, is cut in the interosseous membrane to pass 1 of the FDS tendons.A counter incision in the dorsal forearm is made with use of a long, curved clamp through the interosseous membrane. A Penrose drain is then passed through this tendon portal.Our preferred site for the FDS tendon attachments is around the base of the long metacarpal.FDS = flexor digitorum superficialisPT = pronator teresECRL = extensor carpi radialis longusECRB = extensor carpi radialis brevisFCU = flexor carpi ulnarisEDC = extensor digitorum communisFCR = flexor carpi radialisEIP = extensor indicis propriusEPL = extensor pollicis longusFDP = flexor digitorum profundusMC = metacarpal.

Altres ajuts: acords transformatius de la UAB Background: Liver fibrosis and transient elastography (TE) correlation in hepatitis C virus (HCV)-infected patients with compensated advanced chronic liver disease (cACLD) after the sustained virological response (SVR) is unknown. Aims: To evaluate TE accuracy at identifying cirrhosis 3 years after HCV-eradication. Methods: Prospective, multi-centric study including HCV-cACLD patients before direct-acting antivirals (DAA). Diagnostic accuracy of TE (area under ROC, AUROC) to identify cirrhosis 3 years after SVR was evaluated. Results: Among 746 HCV-infected patients (95.4% with TE ≥10 kPa), 76 (10.2%) underwent a liver biopsy 3 years after SVR. Before treatment, 46 (63%) showed a TE>15 kPa. The TE before DAA was the best variable for predicting cirrhosis (METAVIR, F4) after SVR (AUROC = 0.79). Liver function parameters, serological non-invasive tests (APRI and FIB-4), and TE values improved after SVR. However, liver biopsy 3 years after HCV elimination (median time = 38.4 months) showed cirrhosis in 41 (53.9%). Multivariate analysis (OR (95% CI), P) showed that HCV-genotype 3 (20.81 (2.12-201.47),.009), and TE before treatment (1.21 (1.09-1.34)

Vaccine and antiviral development against SARS-CoV-2 infection or COVID-19 disease would benefit from validated small animal models. Here, we show that transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18 hACE2) represent a susceptible rodent model. K18 hACE2 transgenic mice succumbed to SARS-CoV-2 infection by day 6, with virus detected in lung airway epithelium and brain. K18 ACE2 transgenic mice produced a modest TH1/2/17 cytokine storm in the lung and spleen that peaked by day 2, and an extended chemokine storm that was detected in both lungs and brain. This chemokine storm was also detected in the brain at day 6. K18 hACE2 transgenic mice are, therefore, highly susceptible to SARS-CoV-2 infection and represent a suitable animal model for the study of viral pathogenesis, and for identification and characterization of vaccines (prophylactic) and antivirals (therapeutics) for SARS-CoV-2 infection and associated severe COVID-19 disease., Here, the authors characterize tissue-level SARS-CoV-2 infection and pathogenesis in transgenic mice expressing human angiotensin converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18-hACE2) and show that infection induces lethality, making the K18-hACE2 model suitable for vaccine and therapeutic evaluation.

Pollicization of the index finger allows to reconstruct the hand's ability to pinch and grasp. It has been broadly used to address traumatic loss of the thumb. Today it is the procedure of choice for severe congenital thumb hypoplasia. It allows children prehension of small and large objects and gives the hand a more normal appearance. This is a demanding technique with well-defined and perfected steps that, if carefully performed, can minimize complications.

Purpose The purpose of this study was to evaluate short- to midterm outcomes of patients with acute flaccid myelitis who underwent nerve transfers for restoration of elbow flexion . Methods Patients with a minimum of 10 months of follow up after undergoing nerve transfers to restore elbow flexion were clinically assessed using the Active Movement Scale (AMS). They were evaluated for any postoperative complications , particularly weakness in the distribution of the donor nerve(s). Fifteen of 25 consecutive patients who were treated using this surgical technique were included in the final analysis. Results All patients exhibited poor elbow flexion preoperatively (AMS 0 to 3). At a mean follow up of 17.3 months, 80% (15/25) of patients achieved excellent elbow flexion (AMS 6 or 7); 9 of these 15 had full active range of motion. Two patients achieved good elbow flexion (AMS 5) with antigravity movement to less than 50% of the passive range of motion. No cases of superficial or deep infection were reported, and all patients maintained identical motor function, relative to preoperative status, of the muscles innervated by the donor nerves. Conclusions Nerve transfer surgery has shown promising short- to midterm results for recovery of nerve and muscle function, particularly for the restoration of elbow flexion. We recommend this treatment option for patients not demonstrating clinical improvement after 6 to 9 months of incomplete recovery. Type of study/level of evidence Therapeutic IV.

Several studies have shown the potential use of bone marrow mesenchymal stem cells (BM-MSCs) as a therapeutic approach to infectious diseases. Since BM-MSCs can exert antimicrobial properties and influence the immune response against pathogens, our aim was to study the antimicrobial therapeutic potential of BM-MSCs in an experimental model of paracoccidioidomycosis (PCM). BM-MSCs were isolated from BALB/c donor mice. Paracoccidioides brasiliensis–infected male BALB/c mice were injected with purified BM-MSCs at 8th week post-infection. Mice were sacrificed at 12th week postinfection. Homing of BM-MSCs was confirmed by cellular labeling with fluorescent lipophilic dye and detected by flow cytometry. We found that, in comparison with nontransplanted infected animals, BM-MSCs-treated and P. brasiliensis-infected mice showed a significant increase in (i) fungal burdens, (ii) neutrophils, eosinophils and M2 macrophages counts, and (iii) interleukin (IL)-6, IL-9, GM-CSF, CXCL1, CXCL9, and CCL5 levels, while presenting a decrease in M1 macrophages and Treg cells in lungs. In addition, the histopathological analysis of the lungs showed an increased inflammatory process. This is the first study to our knowledge that evaluates the effects of BM-MSCs treatment in PCM. Our results indicate that the immunoregulatory function of BM-MSCs may be triggered by the interaction with P. brasiliensis, which exacerbates chronic pulmonary inflammatory response. COL0126131 COL0013709

Background: Purpura fulminans is a condition characterized by rapidly evolving skin necrosis and disseminated intravascular coagulation. Early recognition and aggressive supportive management has led to a decrease in its mortality rate, but most of these patients must undergo extensive soft tissue debridement and partial or total limb amputation. There is controversial evidence about the timing of surgery, suggesting that some patients may benefit from delayed debridement with limb preservation. Methods: We present a case of an 86-year-old patient who developed skin necrosis of his four limbs after infectious purpura fulminans. He was treated in the ICU with supportive measures and antibiotic treatment. Surgical debridement was delayed for 4 weeks until necrosis delimitation. Results: Only upper extremity debridement was necessary. Four fingers, including one thumb, were salvaged and successfully treated with semi-occlusive dressing without complications. Conclusion: Early recognition of infectious PF and timely supportive management are important pillars of its treatment. Delayed surgical debridement allows for less aggressive resection and good functional outcome.

New antibiotics are needed to combat rising resistance, with new Mycobacterium tuberculosis (Mtb) drugs of highest priority. Conventional whole-cell and biochemical antibiotic screens have failed. We developed a novel strategy termed PROSPECT (PRimary screening Of Strains to Prioritize Expanded Chemistry and Targets) in which we screen compounds against pools of strains depleted for essential bacterial targets. We engineered strains targeting 474 Mtb essential genes and screened pools of 100-150 strains against activity-enriched and unbiased compounds libraries, measuring > 8.5-million chemical-genetic interactions. Primary screens identified >10-fold more hits than screening wild-type Mtb alone, with chemical-genetic interactions providing immediate, direct target insight. We identified > 40 novel compounds targeting DNA gyrase, cell wall, tryptophan, folate biosynthesis, and RNA polymerase, as well as inhibitors of a novel target EfpA. Chemical optimization yielded EfpA inhibitors with potent wild-type activity, thus demonstrating PROSPECT’s ability to yield inhibitors against novel targets which would have eluded conventional drug discovery.

Itraconazole (ITC) is the drug of choice for treating paracoccidioidomycosis (PCM); nonetheless, patients with the chronic form of this mycosis develop fibrosis, a residual pulmonary abnormality, even after treatment. Recently, we observed that the depletion of neutrophils with a specific monoclonal antibody (mAb-anti-Ly6G) during the chronic stages of PCM was associated with a decrease in the fungal burden, the inflammatory response and a reduction of fibrosis. Herein, we aimed to evaluate the effect of ITC in combination with the mAb-anti-Ly6G in an experimental model of pulmonary PCM. BALB/c male mice were challenged with Paracoccidioides brasiliensis yeasts and treated with the mAb-anti-Ly6G and/or ITC at 4th week post-infection (p.i.) and then sacrificed at 12th week p.i. to assess neutrophil subpopulations, fungal load, collagen, expression of fibrosis- and pro-inflammatory-related genes and histopathology. We observed that combination of ITC/mAb-anti-Ly6G favored the control of infection and diminished the inflammatory response. Of note, such therapeutic strategy reduced the expression of IL-1β, IL-6, IL-17, IL-10, TNF-α, TGF-β1, TGF-β3, GATA-3, RORc, Ahr, MMP-1α, MMP- 8 MMP-15, TIMP-1, and TIMP-2 genes in an additive manner compared to those mice treated with the mAb or ITC alone. Interestingly, ITC induced an increase of type-II neutrophils even in those mice treated with the mAb-anti-Ly6G. These results indicate that combination ITC/mAb-anti-Ly6G reduced the infection and pulmonary fibrosis through down-regulation of inflammatory and pro-fibrotic genes. Additionally, we confirmed the immunomodulatory properties of this antifungal in vivo. This work emphasizes the importance of exploring new potential combination treatments to treat fungal infections. COL0013709 COL0126131

Fractalkine, a chemokine anchored to neurons or peripheral endothelial cells, serves as an adhesion molecule or as a soluble chemoattractant. Fractalkine binds CX3CR1 on microglia and circulating monocytes, dendritic cells, and NK cells. The aim of this study is to determine the role of CX3CR1 in the trafficking and function of myeloid cells to the CNS during experimental autoimmune encephalomyelitis (EAE). Our results show that, in models of active EAE, Cx3cr1−/− mice exhibited more severe neurologic deficiencies. Bone marrow chimeric mice confirmed that CX3CR1 deficiency in bone marrow enhanced EAE severity. Notably, CX3CR1 deficiency was associated with an increased accumulation of CD115+Ly6C−CD11c+ dendritic cells into EAE-affected brains that correlated with enhanced demyelination and neuronal damage. Furthermore, higher IFN-γ and IL-17 levels were detected in cerebellar and spinal cord tissues of CX3CR1-deficient mice. Analyses of peripheral responses during disease initiation revealed a higher frequency of IFN-γ– and IL-17–producing T cells in lymphoid tissues of CX3CR1-deficient as well as enhanced T cell proliferation induced by CX3CR1-deficient dendritic cells. In addition, adoptive transfer of myelin oligodendrocyte glycoprotein35–55-reactive wild-type T cells induced substantially more severe EAE in CX3CR1-deficient recipients when compared with wild-type recipients. Collectively, the data demonstrate that besides its role in chemoattraction, CX3CR1 is a key regulator of myeloid cell activation contributing to the establishment of adaptive immune responses.

The development of an accurate antigen detection assay for the diagnosis of active tuberculosis (TB) would represent a major clinical advance. Here, we demonstrate that the Mycobacterium tuberculosis Rv1681 protein is a biomarker for active TB with potential diagnostic utility. We initially identified, by mass spectroscopy, peptides from the Rv1681 protein in urine specimens from 4 patients with untreated active TB. Rabbit IgG anti-recombinant Rv1681 detected Rv1681 protein in lysates and culture filtrates of M. tuberculosis and immunoprecipitated it from pooled urine specimens from two TB patients. An enzyme-linked immunosorbent assay formatted with these antibodies detected Rv1681 protein in unconcentrated urine specimens from 11/25 (44%) TB patients and 1/21 (4.8%) subjects in whom TB was initially clinically suspected but then ruled out by conventional methods. Rv1681 protein was not detected in urine specimens from 10 subjects with Escherichia coli -positive urine cultures, 26 subjects with confirmed non-TB tropical diseases (11 with schistosomiasis, 5 with Chagas' disease, and 10 with cutaneous leishmaniasis), and 14 healthy subjects. These results provide strong validation of Rv1681 protein as a promising biomarker for TB diagnosis.

Chronic stages of paracoccidioidomycosis (PCM) are characterized by granulomatous lesions which promote the development of pulmonary fibrosis leading to the loss of respiratory function in 50% of patients; in addition, it has been observed that neutrophils predominate during these chronic stages of P. brasiliensis infection. The goal of this study was to evaluate the role of the neutrophil during the chronic stages of experimental pulmonary PCM and during the fibrosis development and tissue repair using a monoclonal specific to this phagocytic cell. Male BALB/c mice were inoculated intranasally with 1.5x106 P. brasiliensis yeast cells. A monoclonal antibody specific to neutrophils was administered at 4 weeks post-inoculation followed by doses every 48h during two weeks. Mice were sacrificed at 8 and 12 weeks post-inoculation to assess cellularity, fungal load, cytokine/chemokine levels, histopathological analysis, collagen and expression of genes related to fibrosis development. Depletion of neutrophils was associated with a significant decrease in the number of eosinophils, dendritic cells, B cells, CD4-T cells, MDSCs and Treg cells, fungal load and levels of most of the pro-inflammatory cytokines/chemokines evaluated, including IL-17, TNF-α and TGF-β1. Recovery of lung architecture was also associated with reduced levels of collagen, high expression of TGF-β3, matrix metalloproteinase (MMP)-12 and -14, and decreased expression of tissue inhibitor metalloproteinase (TIMP)-2, and MMP-8. Depletion of neutrophils might attenuate lung fibrosis and inflammation through down-regulating TGF-β1, TNF-α, IL-17, MMP-8 and TIMP-2. These results suggest that neutrophil could be considered as a therapeutic target in pulmonary fibrosis induced by P. brasiliensis. COL0126131 COL0013709

Neutrophils predominate during the acute phase of theParacoccidioides brasiliensisinfection. Herein, we determined the role of the neutrophil during the early stages of experimental pulmonary paracoccidioidomycosis using a monoclonal antibody (mAb) specific for neutrophils. Male BALB/c mice were inoculated intranasally with1.5×106or2×106P. brasiliensisyeast cells. The mAb was administered 24 h before infection, followed by doses every 48 h until mice were sacrificed. Survival time was evaluated and mice were sacrificed at 48 h and 96 h after inoculation to assess cellularity, fungal load, cytokine/chemokine levels, and histopathological analysis. Neutrophils from mAb-treated mice were efficiently depleted (99.04%). Eighty percent of the mice treated with the mAb and infected with1.5×106yeast cells died during the first two weeks after infection. When mice were treated and infected with2×106yeast cells, 100% of them succumbed by the first week after infection. During the acute inflammatory response significant increases in numbers of eosinophils, fungal load and levels of proinflammatory cytokines/chemokines were observed in the mAb-treated mice. We also confirmed that neutrophils are an important source of IFN-γand IL-17. These results indicate that neutrophils are essential for protection as well as being important for regulating the early inflammatory immune response in experimental pulmonary paracoccidioidomycosis.

One of the many consequences of the pandemic of type 2 diabetes [1] is an increased frequency and severity of infection in diabetic patients, including up to an 8-fold increase in the risk of developing pulmonary tuberculosis [2]. The molecular basis for this susceptibility to tuberculosis is unclear. One possibility is a compromised immune response in diabetic patients that facilitates either primary progressive tuberculosis or reactivation of a latent tuberculosis infection [3]. Studies evaluating immunity to other microbial antigens in diabetic patients suggest that adaptive and innate responses are compromised, particularly in patients with chronic hyperglycemia (measured by elevated glycosylated hemoglobin [HbA1c] level) [4–15]. Immune impairments appear to be reversible with improved glycemic control [10, 16, 17]. Although susceptibility to tuberculosis in diabetic patients has been recognized for more than a century, only now, when we are faced by the current type 2 diabetes epidemic, are we beginning to address the public health impact and potential mechanisms of this association. Cytokines of the innate and adaptive immune systems orchestrate the response to Mycobacterium tuberculosis, with subsequent induction of cellular type 1 immunity, which is critical for protection [18–23]. A recently developed mouse model for diabetes and tuberculosis revealed higher bacterial burden and altered expression of IFN-γ in mice with chronic, but not acute, diabetes [24]. Persistent hyperglycemia apparently plays a significant role in the pathology. In this context, we assessed differences in cytokine secretion in response to an M. tuberculosis antigen in diabetic and nondiabetic patients with tuberculosis, selected from a population of patients known to have elevated rates of type 2 diabetes [25, 26]. To do this, we adapted a relatively simple ex vivo stimulation procedure designed to screen for variations in innate and adaptive immune responses to M. tuberculosis antigens. We hypothesized that, if impairment of the immune response plays a role in susceptibility to tuberculosis in patients with diabetes, we should be able to detect differences in cytokine responses to M. tuberculosis antigens in such patients, particularly in those with poor glycemic control.

OBJECTIVE Microbiological identification of Mycobacterium tuberculosis is insensitive and slow, and clinical distinction of tuberculous meningitis (TBM) from other subacute or chronic meningoenchephalitides (SACM) is difficult. Successful use of highly specific M. tuberculosis serological assays on cerebrospinal fluid has been reported, but their performance for diagnosis in a tuberculosis endemic country where they would be of most value is unclear. We sought to determine the biological basis for the uncertainty in interpretation of antibody detection in the CSF of TBM patients. METHODS We identified prospectively 46 adults with SACM and explored the concordance between TBM diagnosis and detection of highly specific M. tuberculosis antibodies in CSF. The source of antibodies in CSF was explored by evaluating the correlation between antibody titres in CSF with those in serum, or with the albumin quotient. Intrathecal IgG synthesis was assessed by the IgG index. RESULTS Positive antibody titres were more frequent among TBM patients (76%), but were also present in individuals with other SACM (59%). A positive correlation between antibody titres in CSF with those in serum, or with the albumin quotient, supported the leakage of antibodies from plasma to CSF through an increased blood-brain barrier permeability. Intrathecal IgG synthesis was only detected in 35% of the TBM cases. CONCLUSION Plasma antibodies likely synthesized in response to previous tuberculosis infections were a major source of mycobacterial antibodies in CSF due to leakage through an impaired blood-brain barrier. Interpretation of mycobacterial antibodies in CSF of adults for TBM, however specific, must take into account the contribution of antibodies from plasma, and hence, has questionable use for diagnosis.

Objective: The objective of this study is to analyze the factors that may impact on the development of trigger digit (TD) in patients with carpal tunnel release (CTR). Materials and Methods: We conducted a retrospective cohort study of patients who underwent surgery for carpal tunnel syndrome (CTS) and/or TD between January 2004 and May 2014, at our institution. Inclusion criteria were treatment of at least one TD or CTS and age older than 18 years. We performed a manual chart review of the participants and analyzed the following factors: age, gender, previous surgery for CTS or TD, and comorbidities (hypothyroidism and diabetes). In addition, we searched for previous CTS surgery on the same hand of TD symptoms. We performed a follow-up of patients through phone calls, with our primary outcome measure being presence of TD symptoms or need for TD surgery on any hand. The mean follow-up period for this study was 63 months (range, 19-137 months). Statistical Analysis: Patients with CTS were divided into 2 groups: group 1—history of TD surgery or symptoms, and group 2—no TD history. Analysis of associated factors was performed through chi-square and Mann-Whitney tests for an alpha level of significance of .05. An additional analysis was performed of patients with the diagnosis of TD who had a previous CTR surgery on the same hand. Results: In total, 716 charts were reviewed, with 391 patients interviewed and included in the analysis. Of these, 307 patients had history of CTR. There were 106 (27.9%) patients with the diagnosis of TD. Analysis of associated factors showed a significant difference ( P = .01) between the median age of patients with TD, 54 years (range, 32-81), compared with the group of no TD, 51 years (range, 25-86). We found no association between the development of TD and other factors (gender, hypothyroidism, and diabetes). From the total of charts reviewed, 190 patients had TD history or surgery. Only 38 (20%) of them had a previous CTR on the same hand. We found that there was a significantly higher proportion of female patients in the group of TD with prior CTR ( P = .028). The other variables did not show significant differences. Conclusions: This study shows that there is a high number of patients, 27.9%, with CTS surgery that also have history of TD. We found that older patients with CTS had a significantly higher rate of TD. Only 20% of patients who had TD surgery or symptoms during follow-up had a previous CTS surgery on that hand. CTS and TD are conditions which occur in a group of patients with similar characteristics. We did not find a higher rate of TD development in patients with previous CTS surgery.

A degradação oxidativa dos lipídeos é um fator preponderante que limita a vida útil dos alimentos, reduzindo suas qualidades nutricionais e organolépticas. A utilização de antioxidantes durante o processo de fabricação pode diminuir consideravelmente a extensão da oxidação lipídica, desencadeada pela reação de radicais livres. A crescente preocupação pelo consumo de alimentos mais saudáveis e livres de aditivos sintéticos tem recebido maior atenção pelas indústrias, que atualmente tem procurado por alternativas mais naturais, como o uso de antioxidantes provenientes de especiarias, como uma forma promissora de substituição dos compostos sintéticos. O objetivo deste trabalho foi estudar as condições de obtenção de extratos hidroalcoólicos de cravo (Syzygium aromaticum), canela (Cinnamomum verum) e pimenta dedo-de-moça (Capsicum annuum) e sua aplicação em óleos de soja refinado, armazenado em embalagens de vidro, em comparação com amostras adicionadas de antioxidante sintético TBHQ e amostras livres de antioxidantes (controle), durante sete meses, simulando a comercialização em supermercados. Foram verificados também as propriedades antioxidantes dos extratos de especiarias produzidos nas condições selecionadas através das metodologias de DPPH e ABTS. O estudo do efeito da temperatura de extração e do grau de hidratação do etanol sobre o rendimento de compostos fenólicos totais dos extratos destas especiarias foi realizado com aplicação de planejamento experimental e metodologia de superfícies de resposta. As condições para uma extração eficiente dos compostos fenólicos do cravo, da canela e da pimenta foram o emprego de etanol a 49,5 % (v/v). As melhores temperaturas estiveram entre 45 a 50 °C para o cravo e canela, e 60 °C para a pimenta. Os extratos de cravo, canela e pimenta dedo-de-moça preparados nas condições otimizadas, foram adicionados nas proporções de 50 mg kg-1, 100 mg kg-1, 150 mg kg-1 e 200 mg kg-1 às amostras de óleo de soja refinado e submetido a um teste acelerado em estufa a 65 °C juntamente com amostras adicionadas nas mesmas proporções de TBHQ e amostras isentas de antioxidantes (controle), para verificação da concentração mais eficiente no retardar a oxidação. Em seguida, após os resultados do teste de estufa, os óleos adicionados de 100 mg kg-1 de extratos, TBHQ, e isento de antioxidantes foram acondicionados em embalagens de vidro transparente de 250 mL e armazenados sob condições de comercialização (incidência de luz fluorescente por 15 horas / 24 horas e 331,71 Lux). Os resultados de Índice de Peróxido, Acidez e Absortividade na faixa do ultravioleta evidenciaram que os extratos foram capazes de oferecer proteção antioxidante ao óleo de soja refinado em diferentes níveis, sendo que o tratamento adicionado de extrato de cravo foi o que mais se destacou na inibição da oxidação lipídica do óleo de soja, seguido do extrato adicionado de canela e pimenta (p

INTRODUCTION Diabetes knowledge among TB patients can contribute to improved TB treatment outcomes, but lack of diabetes diagnosis awareness is a limitation in developing countries. Given its low cost, the sensitivity of urine glucose dipsticks for diabetes screening in TB patients was assessed. METHODS Glycosuria was assessed in 90 newly diagnosed TB patients (38 with diabetes) in south Texas, USA (n = 20) and northeast Mexico (n = 70) during January 2009-December 2010. RESULTS Glycosuria was detected in 65% of the diabetic patients with chronic hyperglycemia (positive predictive value 91%, negative predictive value 84%). CONCLUSION We propose that TB clinics with limited budgets where portable glucometers may not be available conduct universal screening for diabetes with urine dipsticks. This could be followed by blood glucose or HbA1c testing in the subset of patients requiring confirmation or higher sensitivity assessment, to improve the comanagement of TB and diabetes.

Introduction: Most studies about surgical treatment of carpal tunnel syndrome (CTS) focus on specific population subgroups, worker’s compensation patients, or specific types of surgical treatment. There are no general population studies about epidemiological characterization of surgically treated patients with CTS. Factors such as gender, age, and health insurance status may influence the rate of surgical treatment of CTS. Purpose: Evaluate the influence of epidemiological factors such as gender, age, and health insurance status in the rate of CTS surgery in a mixed health care system. Materials and Methods: Nationwide transversal study of total surgically treated patients with CTS in Chile during 2012. The rate of CTS surgeries was estimated using data collected from Chile’s National Hospital Discharge Records, Public and Private Health Care Systems’ yearly reports on population coverage. Chile’s mixed health care system has a distribution of its population of 81% public, 12.9% private, and 6.1% other insurance. Inclusion criteria: Surgical treatment of CTS (ICD-10 International Statistical Classification of Diseases and Related Health Problems diagnosis G560), age older than 20 years. We analyzed the influence of epidemiological factors such as age, gender, and health insurance status on the rate of CTS surgery. The rate of CTS surgeries was estimated per 1000 habitants in each groups, with their confidence intervals (CI) of 95%. Results: National rate of surgical CTS in patients over 20 years during 2012 was of 0.191 (95% CI, 0.184-0.199). Gender distribution showed higher rate of surgeries in female patients, 0.302 (95% CI, 0.289-0.316), compared with males, 0.077 (95% CI, 0.070-0.084). The age distribution of female patients shows a higher rate of surgeries in the 50- to 59-year group, 0.671 (95% CI, 0.622-0.721). Male patients have a later surgical peak in the 60- to 69-year group, 0.126 (95% CI, 0.098-0.154). The rate of surgical CTS is lower in the public health care system, 0.123 (95% CI, 0.116-0.130), than private insurance, 0.406 (95% CI, 0.379-0.433). The gender distribution was similar in both groups. Conclusions: Health insurance status is the most important factor in the rate of surgical CTS. The access to surgical treatment is 3.3 times higher in private insurance than public system. Gender and age show a higher rate of surgery in female patients in the 50- to 59-year group. This distribution is not influenced by insurance status. National rates of surgical CTS are comparable with reports from the literature. These new data can help understand the population’s behavior and plan resources distribution. It also shows the breach that still has to be covered by the public health care system in terms of surgical treatment of CTS.