The ctpF Gene Encoding a Calcium P-Type ATPase of the Plasma Membrane Contributes to Full Virulence of Mycobacterium tuberculosis.

Identification of alternative attenuation targets of Mycobacterium tuberculosis (Mtb) is pivotal for designing new candidates for live attenuated anti-tuberculosis (TB) vaccines. In this context, the CtpF P-type ATPase of Mtb is an interesting target; specifically, this plasma membrane enzyme is involved in calcium transporting and response to oxidative stress. We found that a mutant of MtbH37Rv lacking ctpF expression (MtbΔctpF) displayed impaired proliferation in mouse alveolar macrophages (MH-S) during in vitro infection. Further, the levels of tumor necrosis factor and interferon-gamma in MH-S cells infected with MtbΔctpF were similar to those of cells infected with the parental strain, suggesting preservation of the immunogenic capacity. In addition, BALB/c mice infected with Mtb∆ctpF showed median survival times of 84 days, while mice infected with MtbH37Rv survived 59 days, suggesting reduced virulence of the mutant strain. Interestingly, the expression levels of ctpF in a mouse model of latent TB were significantly higher than in a mouse model of progressive TB, indicating that ctpF is involved in Mtb persistence in the dormancy state. Finally, the possibility of complementary mechanisms that counteract deficiencies in Ca2+ transport mediated by P-type ATPases is suggested. Altogether, our results demonstrate that CtpF could be a potential target for Mtb attenuation.

Technique for order of preference by similarity to ideal solution (TOPSIS) method for the generation of external preference mapping using rapid sensometric techniques.

BACKGROUND: External preference mapping is a powerful tool to explain consumer preference or rejection. Combining the technique for order of preference by similarity to ideal solution (TOPSIS) multicriteria analysis with rapid descriptive techniques can improve preference map (PREFMAP) results. This study was conducted to compare the PREFMAPs generated with rapid descriptive flash profile (FP), check-all-that-apply (CATA), and Napping® versus PREFMAPs constructed with FP-TOPSIS, CATA-TOPSIS, and Napping-TOPSIS. RESULTS: Only 38.46%, 63.66%, and 42% of sensory attributes initially generated by FP, CATA, and Napping techniques respectively were considered for the determination of their weight W and allocation as positive or negative in the TOPSIS technique. The PREFMAPs constructed with FP-TOPSIS, CATA-TOPSIS, and Napping-TOPSIS presented a better explanation of the preference and rejection than the PREFMAPs directly generated with rapid sensory techniques. The results of the multiple factor analysis and coefficient Rv indicated similarities in the sensory vocabularies used after the TOPSIS technique. CONCLUSION: The combination of the TOPSIS technique with rapid sensory techniques is a reliable alternative for the construction of PREFMAPs in order to identify the sensory attributes responsible for preference and rejection of food products. © 2020 Society of Chemical Industry.

Effect of photobiomodulation on the stability and displacement of orthodontic mini-implants submitted to immediate and delayed loading: a clinical study.

The aim of this study was to evaluate the effect of photobiomodulation (PBM) on the stability and displacement of orthodontic mini-implants (MIs) submitted to loading. Forty-eight and 35 mini-implants (1.5 × 8 × 1 mm) were assessed for stability and displacement, respectively (19 patients). MIs were allocated according to the intervention in 1-PBM + immediate loading (IL), 2-PBM + delayed loading (DL) (four weeks after implantation), 3-IL only, and 4-DL only. PBM (Therapy XT, DCM) was implemented using a red emission (660 nm, 4 J/cm2, 0.1 W, 20 s) immediately after implantation (day 0) and infrared emissions (808 nm; 8 J/cm2, 0.1 W, 40 s) in the following appointments every 48-72 h during two weeks (days 2, 4, 7, 9, 11, and 14). Loading of 150 gF was applied during three months for all MIs. The stability was assessed by resonance frequency analysis (Osstell ISQ), and images from Cone beam computed tomography were evaluated to determine the amount of the displacement of the MI's head. MIs from the PBM groups presented lower loss of stability (P = 0.0372). When the analysis considered the loading protocol as an additional variable, group two showed the lowest loss of stability, being significantly different from groups that did not receive PBM (P = 0.0161). There was no difference between groups two and four during the period without loading (P > 0.05). DL groups presented lower loss when the effective period of loading was assessed, independently of the application of PBM (P < 0.0001). All groups showed displacement of the MIs head without significant differences (P > 0.05). DL potentiated the effect of PBM, decreasing the loss of stability.

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Introduction).

BACKGROUND: The field of new biological agents is increasing exponentially over the past years, thus making prevention and management of associated infectious complications a challenge for nonspecialized clinicians. AIMS: The present consensus document is an initiative of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) aimed at analysing, from an infectious diseases perspective, the safety of targeted and biological therapies. SOURCES: Computer-based Medline searches with MeSH terms pertaining to each agent or therapeutic family. CONTENT: The document is structured in sections according to the targeted site of action of each drug class: proinflammatory cytokines; interleukins, immunoglobulins and other soluble immune mediators; cell surface receptors and associated signaling pathways; intracellular signaling pathways; lymphoma and leukaemia cells surface antigens; and other targeted therapies. A common outline is followed for each agent: summary of mechanism of action, approved indications and common off-label uses; expected impact on the host's susceptibility to infection; available clinical evidence (i.e. pivotal clinical trials, postmarketing studies, case series and case reports); and suggested prevention and risk minimization strategies. The methodologic and practical difficulties of assessing the specific risk posed by a given agent are also discussed. IMPLICATIONS: This ESGICH consensus document constitutes not only a comprehensive overview of the molecular rationale and clinical experience on the risk of infection associated with approved targeted therapies but also an attempt to propose a series of recommendations with the purpose of guiding physicians from different disciplines into this emerging framework.

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Immune checkpoint inhibitors, cell adhesion inhibitors, sphingosine-1-phosphate receptor modulators and proteasome inhibitors).

BACKGROUND: The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) consensus document on the safety of targeted and biological therapies. AIMS: To review, from an infectious diseases perspective, the safety profile of immune checkpoint inhibitors, LFA-3-targeted agents, cell adhesion inhibitors, sphingosine-1-phosphate receptor modulators and proteasome inhibitors, and to suggest preventive recommendations. SOURCES: Computer-based Medline searches with MeSH terms pertaining to each agent or therapeutic family. CONTENT: T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death (PD)-1/PD-1 ligand 1 (PD-L1)-targeted agents do not appear to intrinsically increase the risk of infection but can induce immune-related adverse effects requiring additional immunosuppression. Although CD4+ T-cell lymphopenia is associated with alefacept, no opportunistic infections have been observed. Progressive multifocal leukoencephalopathy (PML) may occur during therapy with natalizumab (anti-α4-integrin monoclonal antibody (mAb)) and efalizumab (anti-CD11a mAb), but no cases have been reported to date with vedolizumab (anti-α4ß7 mAb). In patients at high risk for PML (positive anti-JC polyomavirus serology with serum antibody index >1.5 and duration of therapy ≥48 months), the benefit-risk ratio of continuing natalizumab should be carefully considered. Fingolimod induces profound peripheral blood lymphopenia and increases the risk of varicella zoster virus (VZV) infection. Prophylaxis with (val)acyclovir and VZV vaccination should be considered. Proteasome inhibitors also increase the risk of VZV infection, and antiviral prophylaxis with (val)acyclovir is recommended. Anti-Pneumocystis prophylaxis may be considered in myeloma multiple patients with additional risk factors (i.e. high-dose corticosteroids). IMPLICATIONS: Clinicians should be aware of the risk of immune-related adverse effects and PML in patients receiving immune checkpoint and cell adhesion inhibitors respectively.

[Leptospirosis in a family after whitewater rafting in Thailand]. / Leptospirose famitiate apres rafting en Thaïlande.

Leptospirosis is a zoonosis found worldwide, with an incidence that is approximately 10 times higher in the tropics than in temperate regions. The main reservoir of leptospirosis is the rat and human infection usually results from exposure to infected animal urine or tissues. Only 10% of cases are symptomatic. We present here two confirmed and two probable cases of leptospirosis in a family returning from whitewater rafting in Thailand, illustrating the wide variety of the clinical manifestations of this infection. Two of the patients were hospitalized and presented a probable Jarisch-Herxheimer reaction after initiation of beta-lactam therapy. The two others patients were treated empirically with doxycycline. We discuss here some relevant aspects of the epidemiology, clinical manifestations, therapy and the challenge of an early diagnosis of leptospirosis.

Impact of enterococcal colonization and infection in solid organ transplantation recipients from the Swiss transplant cohort study.

BACKGROUND: The burden of enterococcal infections has increased over the last decades with vancomycin-resistant enterococci (VRE) being a major health problem. Solid organ transplantation is considered as a risk factor. However, little is known about the relevance of enterococci in solid organ transplantation recipients in areas with a low VRE prevalence. METHODS: We examined the epidemiology of enterococcal events in patients followed in the Swiss Transplant Cohort Study between May 2008 and September 2011 and analyzed risk factors for infection, aminopenicillin resistance, treatment, and outcome. RESULTS: Of the 1234 patients, 255 (20.7%) suffered from 392 enterococcal events (185 [47.2%] infections, 205 [52.3%] colonizations, and 2 events with missing clinical information). Only 2 isolates were VRE. The highest infection rates were found early after liver transplantation (0.24/person-year) consisting in 58.6% of Enterococcus faecium. The highest colonization rates were documented in lung transplant recipients (0.33/person-year), with 46.5% E. faecium. Age, prophylaxis with a betalactam antibiotic, and liver transplantation were significantly associated with infection. Previous antibiotic treatment, intensive care unit stay, and lung transplantation were associated with aminopenicillin resistance. Only 4/205 (2%) colonization events led to an infection. Adequate treatment did not affect microbiological clearance rates. Overall mortality was 8%; no deaths were attributable to enterococcal events. CONCLUSIONS: Enterococcal colonizations and infections are frequent in transplant recipients. Progression from colonization to infection is rare. Therefore, antibiotic treatment should be used restrictively in colonization. No increased mortality because of enterococcal infection was noted.

Nutritional effects of implant therapy in edentulous patients--a systematic review.

PURPOSE: The aim of this study was to present all the relevant studies that have evaluated, with valid scientific methodology, the possible physical and nutrient intake improvement of edentulous subjects rehabilitated with removable and supported or retained implant denture, without restriction of suprastructure modalities, compared with those wearing conventional removable dentures. METHODS AND MATERIALS: Several electronic databases (Pubmed, Medline-Medline In-Process, Cochrane Library Database, Embase, and Lilacs) were searched, without language limitation. References from the selected articles were also hand searched. Abstracts which appeared to fulfill the initial selection criteria (comparison of nutritional state between conventional removable and supported or retained implant denture wearers) were selected by consensus and their original articles were then retrieved. Clinical trials that included anthropometric measurements or nutrient intake in removable and supported or retained implant denture wearers without syndrome and systemic influences, nor presenting surgical or other simultaneous treatment, which could affect the integrity during the evaluation period were finally selected. RESULTS: Only 5 articles met the selection criteria. Two studies (randomized clinical trials and prospective) found inadequate nutrient intake after treatment. One randomized clinical trial presented an improvement in nutritional state after treatment. One cross-sectional study showed an adequate nutritional state before and after treatment. These 4 studies found no significant difference between implant and conventional treatments. Finally, 1 cross-sectional study presented a difference between treatments, showing that the risk of malnutrition was higher for removable complete denture wearers. CONCLUSION: Considering the available evidence, the effect on the nutritional state in edentulous subjects treated with implant therapy is similar to the 1 obtained with conventional removable dentures. This effect does not necessarily mean an optimum nutritional state, which also depends on other factors not related to prosthodontic treatment.

Terapia antimicrobiana ambulatoria en sepsis comunitarias / Ambulatory antibacterial therapy in community sepsis

Se realizó un estudio sobre la prescripción de antimicrobianos a pacientes en régimen ambulatorio, con el objetivo de evaluar la indicación de estos fármacos en la Farmacia Comunitaria de Servicios Hospitalarios adjunta al Hospital Militar “Cdte. Manuel Fajardo Rivero” en Santa Clara. La muestra analizada incluyó a 1 231 pacientes que requirieron de una farmacoterapia antimicrobiana entre octubre y diciembre de 2003. De ellos, 72,22 por ciento provinieron del cuerpo de guardia, 19,17 por ciento de las consultas externas y 8,61 por ciento de consultorios médicos cercanos. Fue diseñado un anexo para recopilar datos personales, clínicos y farmacológicos de interés. Las infecciones respiratorias (50,93 por ciento) y las urinarias (25,75 por ciento) fueron las que generaron mayor número de prescripciones. Ciprofloxacino y macrólidos (entre estos últimos, de manera marcada, azitromicina) fueron los más indicados, seguidos por los β-lactámicos. La prescripción fue altamente empírica (90,83 por ciento). Se detectaron 48 pacientes con pautas de dosificación superiores a las requeridas, todos con azitromicina(AU)

Ciprofloxacino en el tratamiento ambulatorio / Cyprofloxacine in ambulatory treatment

Se realizó un estudio prospectivo descriptivo sobre la prescripción de ciprofloxacino (250 mg tabletas), con el objetivo de evaluar la indicación de este antimicrobiano en la Farmacia Comunitaria de Servicios Hospitalarios del Hospital "Manuel Fajardo Rivero" de Santa Clara. La muestra estudiada incluyó a 273 pacientes, a los cuales se les indicó tratamiento ambulatorio con dicho fármaco en el período comprendido desde noviembre de 2002 hasta enero de 2003. Fueron diseñados dos anexos (expediente de antibiótico, e información sobre reacciones adversas al medicamento y asociaciones medicamentosas), para recopilar tanto datos personales del paciente como sobre aspectos clínicos y farmacológicos del tratamiento instaurado. Se determinó que las sepsis respiratorias (46,52 por ciento) y las urinarias (39,56 por ciento) constituyeron las enfermedades más tratadas con este antibiótico. El uso de esta fluorquinolona estuvo basado en resultados microbiológicos en un 30,40 por ciento de las indicaciones, como alternativa al fracaso terapéutico e hipersensibilidad a otros antimicrobianos en un 16,49 por ciento, y resultó empírica en el 53,11 por ciento de los casos. Se informó un 100 por ciento de efectividad y bajo índice (8,54 por ciento) de posibles reacciones adversas; teofilina y glibenclamida fueron los fármacos con los cuales más se asoció el ciprofloxacino(AU)

Ciprofloxacino en el tratamiento ambulatorio / Cyprofloxacine in ambulatory treatment

Se realizó un estudio prospectivo descriptivo sobre la prescripción de ciprofloxacino (250 mg tabletas), con el objetivo de evaluar la indicación de este antimicrobiano en la Farmacia Comunitaria de Servicios Hospitalarios del Hospital "Manuel Fajardo Rivero" de Santa Clara. La muestra estudiada incluyó a 273 pacientes, a los cuales se les indicó tratamiento ambulatorio con dicho fármaco en el período comprendido desde noviembre de 2002 hasta enero de 2003. Fueron diseñados dos anexos (expediente de antibiótico, e información sobre reacciones adversas al medicamento y asociaciones medicamentosas), para recopilar tanto datos personales del paciente como sobre aspectos clínicos y farmacológicos del tratamiento instaurado. Se determinó que las sepsis respiratorias (46,52 por ciento) y las urinarias (39,56 por ciento) constituyeron las enfermedades más tratadas con este antibiótico. El uso de esta fluorquinolona estuvo basado en resultados microbiológicos en un 30,40 por ciento de las indicaciones, como alternativa al fracaso terapéutico e hipersensibilidad a otros antimicrobianos en un 16,49 por ciento, y resultó empírica en el 53,11 por ciento de los casos. Se informó un 100 por ciento de efectividad y bajo índice (8,54 por ciento) de posibles reacciones adversas; teofilina y glibenclamida fueron los fármacos con los cuales más se asoció el ciprofloxacino