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We propose and experimentally demonstrate a simple, low-cost optical ultra-wide band (UWB) pulse generation method. A gain-switched laser pulse is dispersed by optical fiber propagation and upconverted to the center of the US Federal Communications Commission (FCC) mask using an optical intensity modulator. The generated UWB pulses comply with the FCC mask with relatively high power efficiencies. We also show that the optical fiber can be replaced with a fiber Bragg grating filter to make the transmitter compact. Wireless propagation of the UWB impulses is investigated by offline signal processing. A linear receiver and an energy detector are implemented. The linear filter shows a better BER performance, particularly in worse channel conditions. We reach the FEC limit of 10-3 after 3.5 m of wireless propagation at 856 Mb/s. [ABSTRACT FROM PUBLISHER]

Resumen Se estudian los efectos de la histamina y de la 5 hidroxitriptamina sobre el tono de las preparaciones aisladas de esófago, estómago e intestino delgado de Liolaemus gravenhorsti. En los tres segmentos las drogas produjeron un aumento del tono basal que fue proporcional al incremento de las concentraciones locales y el esófago presentó la mayor sensibilidad a ambas aminas. El efecto constrictor de la histamina fue antagonizado por la cloroprofenpiridamina pero no por la cimetidina, lo que indicaría la presencia de los receptores histaminérgicos H1 en las mencionadas estructuras. La metisergida bloqueó parcialmente el efecto de la 5 hidroxitriptamina. Zusammenfassung Auswirkung biogener Amine (Histamin und 5-Hydroxytryptamin) auf die Motilität der glatten Muskulatur des Verdauungstrakts von Iguaniden ( Liolaemus gravenhorsti, Reptilia-Squamata-Iguanidae) Die Wirkung von Histamin und 5-Hydroxytryptamin auf den Tonus von isolierten Abschnitten des Ösophagus, Magens und Dünndarms von Liolaemus gravenhorsti wurden untersucht. Die Substanzen bewirkten in allen drei Abschnitten eine Tonuserhöhung, proportional zur Konzentration. Der Ösophagus zeigte die höchste Empfindlichkeit für beide Amine. Chlorprofenpyridamin, nicht aber Cimetidin, erwies sich als Antagonist zur konstriktorischen Wirkung der Histamine. Es wird daher angenommen, daß in den untersuchten Segmenten Histamin-H1-Rezeptoren vorhanden sind. Methysergid blok-kierte teilweise die Wirkung des 5-Hydroxytryptamins. Summary Effect of biogenic amines (histamine and 5-hydroxy tryptamine) on the motility of digestive tract smooth muscle of Iguanidae ( Liolaemus gravenhorsti, Reptilia-Squamata-Iguanidae) The effect of histamine and 5-hydroxytryptamine on the tonus of isolated segments of oesophagus, stomach and duodenum of Liolaemus gravenhorsti was studied. They produced increased tonus on all three regions, the increase being proportional to the concentration. The oesophagus showed the highest susceptibility to both amines. Chlorprofenpyrimidine, but not cimetidine, showed an antagonistic action to the constrictor effect of histamine. It is concluded that in the segments examined there are histamine-H1 receptors. Metihusergide partially blocked the effect of 5-hydroxytryptamine. [ABSTRACT FROM AUTHOR]

Abstract Background Conventional methods for susceptibility testing require several months before results can be reported. However, rapid methods to determine drug susceptibility have been developed recently. Phage assay have been reported as a rapid useful tools for antimicrobial susceptibility testing. The aim of this study was to apply the Phage assay for rapid detection of resistance on Mycobacterium tuberculosis strains in Cuba. Methods Phage D29 assay was performed on 102 M. tuberculosis strains to detect rifampicin resistance. The results were compared with the proportion method (gold standard) to evaluate the sensitivity and specificity of Phage assay. Results Phage assay results were available in 2 days whereas Proportion Methods results were obtain in 42 days. A total of 44 strains were detected as rifampicin resistant by both methods. However, one strains deemed resistant by Proportion Methods was susceptible by Phage assay. The sensitivity and specificity of Phage assay were 97.8 % and 100% respectively. Conclusion Phage assay provides rapid and reliable results for susceptibility testing; it's easy to perform, requires no specialized equipment and is applicable to drug susceptibility testing in low income countries where tuberculosis is a major public health problem.

Falling is a major cause of morbidity, and is often caused by a decrease in postural stability. A key component of postural stability is whole-body centroidal angular momentum, which can be influenced by control moment gyroscopes. In this proof-of-concept study, we explore the influence of our wearable robotic gyroscopic actuator "GyroPack" on the balance performance and gait characteristics of non-impaired individuals (seven female/eight male, 30 ± 7 years, 68.8 ± 8.4 kg). Participants performed a series of balance and walking tasks with and without wearing the GyroPack. The device displayed various control modes, which were hypothesised to positively, negatively, or neutrally impact postural control. When configured as a damper, the GyroPack increased mediolateral standing time and walking distance, on a balance beam, and decreased trunk angular velocity variability, while walking on a treadmill. When configured as a negative damper, both peak trunk angular rate and trunk angular velocity variability increased during treadmill walking. This exploratory study shows that gyroscopic actuators can influence balance and gait kinematics. Our results mirror the findings of our earlier studies; though, with more than 50% mass reduction of the device, practical and clinical applicability now appears within reach.

Three-dimensional (3D) cameras used for gait assessment obviate the need for bodily markers or sensors, making them particularly interesting for clinical applications. Due to their limited field of view, their application has predominantly focused on evaluating gait patterns within short walking distances. However, assessment of gait consistency requires testing over a longer walking distance. The aim of this study is to validate the accuracy for gait assessment of a previously developed method that determines walking spatiotemporal parameters and kinematics measured with a 3D camera mounted on a mobile robot base (ROBOGait). Walking parameters measured with this system were compared with measurements with Xsens IMUs. The experiments were performed on a non-linear corridor of approximately 50 m, resembling the environment of a conventional rehabilitation facility. Eleven individuals exhibiting normal motor function were recruited to walk and to simulate gait patterns representative of common neurological conditions: Cerebral Palsy, Multiple Sclerosis, and Cerebellar Ataxia. Generalized estimating equations were used to determine statistical differences between the measurement systems and between walking conditions. When comparing walking parameters between paired measures of the systems, significant differences were found for eight out of 18 descriptors: range of motion (ROM) of trunk and pelvis tilt, maximum knee flexion in loading response, knee position at toe-off, stride length, step time, cadence; and stance duration. When analyzing how ROBOGait can distinguish simulated pathological gait from physiological gait, a mean accuracy of 70.4%, a sensitivity of 49.3%, and a specificity of 74.4% were found when compared with the Xsens system. The most important gait abnormalities related to the clinical conditions were successfully detected by ROBOGait. The descriptors that best distinguished simulated pathological walking from normal walking in both systems were step width and stride length. This study underscores the promising potential of 3D cameras and encourages exploring their use in clinical gait analysis.

The main goal of the treatment for acute myocardial infarction is to achieve reperfusion of the affected myocardial tissue, with percutaneous coronary angioplasty being the gold standard procedure. However, this strategy has been associated with additional heart damage termed "lethal reperfusion injury," which is responsible for up to half of the final infarct size. Among the possible underlying mechanisms that are likely to explain this damage, studies suggest that oxidative stress plays a key role. Although this has not been translated into clinical benefits in most studies, recent preclinical studies reported promising results and a possible synergy with the combined use of vitamin C (VC), N-acetylcysteine (NAC), and deferoxamine (DFO). However, to implement a combined therapy with these drugs for patients requires further studies to understand their pharmacokinetic properties. Available data of the clinical trials have not been validated by looking into the pharmacokinetics in their design. Therefore, this article presents an update and comparison of the evidence for the efficacy of these administration schemes for each drug in cardioprotection, their pharmacokinetic properties and mechanisms of action for their use against "lethal reperfusion injury." To achieve a cardioprotective effect using a new pharmacological strategy before the onset of reperfusion, it is helpful to consider the pharmacokinetics of each drug. In this regard, to design a fast and short pharmacologic therapeutic strategy, theoretically VC and DFO concentrations could be modeled by a one-compartment model whereas NAC could be modeled by a three-compartment model with an initial short half-life., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Trunk motor control is essential for the proper functioning of the upper extremities and is an important predictor of gait capacity in children with delayed development. Early diagnosis and intervention could increase the trunk motor capabilities in later life, but current tools used to assess the level of trunk motor control are largely subjective and many lack the sensitivity to accurately monitor development and the effects of therapy. Inertial measurement units could yield an objective quantitative assessment that is inexpensive and easy-to-implement. We hypothesized that root mean square of jerk, a proxy for movement smoothness, could be used to distinguish age and thereby presumed motor development. We attached a sensor to the trunks of six young children with no known developmental deficits. Root mean square of jerk decreases with age, up to 24 months, and is correlated to a more established method, i.e., center-of-pressure velocity, as well as other standard inertial measurement unit outputs. This metric therefore shows potential as a method to differentiate trunk motor control levels.

Bisphenol A (BPA) is one of the most studied and most controversial chemicals used by the food packaging industry, because of its endocrine disruptive properties. Part of the controversy is due to the uncertainty that surrounds the effects of BPA on the endocrine system. Uncertainty includes data gaps, methodological hurdles, incompatibilities between toxicology and endocrinology-based approaches, and so on. In this article, we analyze how uncertainty has been conceptualized and treated. We focus on the European Food Safety Authority assessments of BPA, and study how exposure and hazard assessments have evolved over time, how uncertainty has been analyzed, and how the agency responded to controversies. Results show that in the attempt to reduce knowledge gaps, assessments have become progressively larger, including more references, evidence, and effects. There is a tendency toward greater precisions and specification of results, and toward protocolization of all processes included in the assessment (from literature review, to uncertainty assessments, and public consultation). Yet, the uncertainty has not diminished following the increase in evidence. We argue that the strategy used to reduce uncertainty within risk assessment, namely including more variables, studies, data, and methods, amplifies the uncertainty linked to indeterminacy (as more results increase the fragmentation of the knowledge base due to the open-ended nature of complex issues) and ambiguity (as complexity gives way to multiple nonequivalent interpretations of results). For this reason, it is important to consider different types of uncertainty and how these uncertainties interact with each other., (© 2021 The Authors. Risk Analysis published by Wiley Periodicals LLC on behalf of Society for Risk Analysis.)

Gyroscopic actuators are appealing for wearable applications due to their ability to provide overground balance support without obstructing the legs. Multiple wearable robots using this actuation principle have been proposed, but none has yet been evaluated with humans. Here we use the GyBAR, a backpack-like prototype portable robot, to investigate the hypothesis that the balance of both healthy and chronic stroke subjects can be augmented through moments applied to the upper body. We quantified balance performance in terms of each participant's ability to walk or remain standing on a narrow support surface oriented to challenge stability in either the frontal or the sagittal plane. By comparing candidate balance controllers, it was found that effective assistance did not require regulation to a reference posture. A rotational viscous field increased the distance healthy participants could walk along a 30mm-wide beam by a factor of 2.0, compared to when the GyBAR was worn but inactive. The same controller enabled individuals with chronic stroke to remain standing for a factor of 2.5 longer on a narrow block. Due to its wearability and versatility of control, the GyBAR could enable new therapy interventions for training and rehabilitation.

Microbes have developed mechanisms to resist the host immune defenses and some elicit antitumor immune responses. About 6 million people are infected with Trypanosoma cruzi, the protozoan agent of Chagas' disease, the sixth neglected tropical disease worldwide. Eighty years ago, G. Roskin and N. Klyuyeva proposed that T. cruzi infection mediates an anti-cancer activity. This observation has been reproduced by several other laboratories, but no molecular basis has been proposed. We have shown that the highly pleiotropic chaperone calreticulin (TcCalr, formerly known as TcCRT), translocates from the parasite ER to the exterior, where it mediates infection. Similar to its human counterpart HuCALR (formerly known as HuCRT), TcCalr inhibits C1 in its capacity to initiate the classical pathway of complement activation. We have also proposed that TcCalr inhibits angiogenesis and it is a likely mediator of antitumor effects. We have generated several in silico structural TcCalr models to delimit a peptide (VC-TcCalr) at the TcCalr N-domain. Chemically synthesized VC-TcCalr did bind to C1q and was anti-angiogenic in Gallus gallus chorioallantoic membrane assays. These properties were associated with structural features, as determined in silico. VC-TcCalr, a strong dipole, interacts with charged proteins such as collagen-like tails and scavenger receptors. Comparatively, HuCALR has less polarity and spatial stability, probably due to at least substitutions of Gln for Gly, Arg for Lys, Arg for Asp and Ser for Arg that hinder protein-protein interactions. These differences can explain, at least in part, how TcCalr inhibits the complement activation pathway and has higher efficiency as an antiangiogenic and antitumor agent than HuCALR., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Introduction: Gliomas are tumors of the central nervous system. Despite new classifications, they are still divided in low and high-grade gliomas, being the latter of greater malignancy. The degree of malignancy is directly related with the angiogenic activity in tumoral tissues. We measured VEGF concentrations and angiogenic capacity in cerebrospinal fluid (CSF) from patients with high and low-grade gliomas. The purpose of this study was to find a biomarker that contributes in the differential diagnosis and prognosis of gliomas., Methods: CSF was obtained from 19 individuals: 8 with low-grade gliomas, 6 with high-grade gliomas and 5 controls. VEGF concentration in CSF was measured by ELISA and the angiogenic capacity was measured by chick chorioallantoic membrane (CAM) test., Results: The VEGF concentration was higher in patients with high-grade gliomas, compared to patients with low-grade gliomas and controls (2860 pg/mL ± 975 vs. 182.6 ± 37.1 and 47.4 ± 0.4, respectively). On the other hand, CSF from patients with high-grade gliomas generated a higher microvascular density (MVD) than patients with low-grade gliomas and controls (13.23 ± 0.6 vessels/9000μm 2 vs. 9.3 ± 0.3 and 7.92 ± 0.2, respectively). Interestingly, there was not statistical differences in both VEGF levels and angiogenic capacity in patients with low-grade gliomas and controls., Conclusion: Together VEGF levels and angiogenic capacity in CSF can be used as a biological marker of gliomas malignancy.

Balancing the upper body is pivotal for upright and efficient gait. While models have identified potentially useful characteristics of biarticular thigh muscles for postural control of the upper body, experimental evidence for their specific role is lacking. Based on theoretical findings, we hypothesised that biarticular muscle activity would increase strongly in response to upper-body perturbations. To test this hypothesis, we used a novel Angular Momentum Perturbator (AMP) that, in contrast to existing methods, perturbs the upper-body posture with only minimal effect on Centre of Mass (CoM) excursions. The impulse-like AMP torques applied to the trunk of subjects resulted in upper-body pitch deflections of up to 17° with only small CoM excursions below 2 cm. Biarticular thigh muscles (biceps femoris long head and rectus femoris) showed the strongest increase in muscular activity (mid- and long-latency reflexes, starting 100 ms after perturbation onset) of all eight measured leg muscles which highlights the importance of biarticular muscles for restoring upper-body balance. These insights could be used for improving technological aids like rehabilitation or assistive devices, and the effectiveness of physical training for fall prevention e.g. for elderly people.

INTRODUCTION Systematic surveillance of antituberculosis drug resistance allows identification of multidrug-resistant and extensively drug-resistant isolates of Mycobacterium tuberculosis. Surveillance studies of antituberculosis drug resistance systematically conducted in Cuba for over 15 years have revealed low circulation of multidrug-resistant tuberculosis, under 1% in new cases. OBJECTIVE Characterize antituberculosis drug resistance in isolates of M. tuberculosis recovered from patients with pulmonary tuberculosis in Cuba in 2012-2014. METHODS The nitrate reductase assay was used to test 997 isolates of M. tuberculosis for sensitivity to isoniazid and rifampicin. Isolates identified as multidrug resistant were tested for sensitivity to isoniazid, rifampicin, streptomycin, ethambutol, ofloxacin, amikacin, kanamycin and capreomycin by the proportion method, as well as genetic resistance mutations in rpoB, katG, inhA, gyrA, rrs and embB genes, using GenoType MTBDRplus and MTBDRsl commercial kits. RESULTS Some 95.6% of isolates from new cases and 89.6% of isolates from previously treated patients were sensitive to isoniazid and rifampicin. Multidrug resistance was found in 0.8% of new and 5.2% of previously treated patients, a statistically significant difference. One extensively drug-resistant isolate was detected among previously treated cases. All isolates examined with the molecular method had mutations in the rpoB gene, which is associated with resistance to rifampicin; only seven showed mutations in the katG gene and one in the inhA gene associated with isoniazid resistance. In one isolate, we found mutations in both gyrA and rrs genes, which are associated with resistance to fluoroquinolones and second-line injectable drugs and therefore, extensive resistance. CONCLUSIONS Results corroborate the low frequency of multidrug-resistant and extensively resistant M. tuberculosis strains in Cuba and highlight the need for continuous improvement of surveillance of antituberculosis drug resistance in Cuba. KEYWORDS Mycobacterium tuberculosis, multidrug resistance, extensively drug-resistant tuberculosis, Cuba.

The Michoacán state is characterized by the existence of important environmental heterogeneity in terms of climate, topography and types of vegetation, which includes the worldwide endangered tropical dry forest. Some reports indicating the presence of the six species of felids occurring in Mexico in this region have been made; however, evidence to support these reports is scant, and filling this lack of information is particularly critical in the case of threatened species or habitats. The aim of this study was to systematize and analyze data distribution patterns of felids in the state of Michoacán, in the Central-Western Mexico. We conducted a review of literature and databases to compile species presence records in the study region. Moreover, we analyzed data obtained from ten years of field work conducted in the region, in which complementary methods (detection of direct and indirect evidence of species occurrence along transects, camera-trapping and interviews to local people) were applied to detect the presence of felid species. We compiled a total of 29 presence records of felids in the region from our review. Additionally, field work, which accumulated 1,107.5 km of walked transects, and 8 699 camera-trap days, produced 672 records of species presence. Lynx rufus was the species with the lowest number of records and the most restricted distribution. In contrast, the species with the greatest number of records was Leoparduspardalis (n = 343). In general, 89% of felids records occurred below 1,000 masl. Overall mean annual temperature of presence records was 24 °C and mean annual precipitation was 1,040 mm. The species whose presence records showed the most distinctive pattern, in terms of temperature and precipitation associated, was L. rufus (15.8 ± 1.3°C and 941 ± 171 mm). Results of a cluster analysis showed that areas supporting different combinations of eco-regions and types of vegetation could be grouped in five clusters having different assemblages of felid species and camera-trapping records. This study results useful to garner a more comprehensive view of the distribution patterns of felids in a region with important environmental contrasts and subjected to an increased human pressure. Moreover, this study provides insights that further our understanding of the relationship between environmental variables and felid distribution patterns which may have an impact for conservation and management strategies at the local and regional levels.

Early in cancer development, tumour cells express vascular endothelial growth factor (VEGF), a secreted molecule that is important in all stages of angiogenesis, an essential process that provides nutrients and oxygen to the nascent tumor and thereby enhances tumor-cell survival and facilitates growth. Survivin, another protein involved in angiogenesis, is strongly expressed in most human cancers, where it promotes tumor survival by reducing apoptosis as well as favoring endothelial cell proliferation and migration. The mechanisms by which cancer cells induce VEGF expression and angiogenesis upon survivin up-regulation remain to be fully established. Since the PI3K/Akt signalling and β-catenin-Tcf/Lef dependent transcription have been implicated in the expression of many cancer-related genes, including survivin and VEGF, we evaluated whether survivin may favor VEGF expression, release from tumor cells and induction of angiogenesis in a PI3K/Akt-β-catenin-Tcf/Lef-dependent manner. Here, we provide evidence linking survivin expression in tumor cells to increased β-catenin protein levels, β-catenin-Tcf/Lef transcriptional activity and expression of several target genes of this pathway, including survivin and VEGF, which accumulates in the culture medium. Alternatively, survivin downregulation reduced β-catenin protein levels and β-catenin-Tcf/Lef transcriptional activity. Also, using inhibitors of PI3K and the expression of dominant negative Akt, we show that survivin acts upstream in an amplification loop to promote VEGF expression. Moreover, survivin knock-down in B16F10 murine melanoma cells diminished the number of blood vessels and reduced VEGF expression in tumors formed in C57BL/6 mice. Finally, in the chick chorioallantoid membrane assay, survivin expression in tumor cells enhanced VEGF liberation and blood vessel formation. Importantly, the presence of neutralizing anti-VEGF antibodies precluded survivin-enhanced angiogenesis in this assay. These findings provide evidence for the existance of a posititve feedback loop connecting survivin expression in tumor cells to PI3K/Akt enhanced β-catenin-Tcf/Lef-dependent transcription followed by secretion of VEGF and angiogenesis.

Background: During the last few years it has been shown in several laboratories that Celecoxib (Cx), a non-steroidal anti-inflammatory agent (NSAID) normally used for pain and arthritis, mediates antitumor and antiangiogenic effects. However, the effects of this drug on a tumor cell line resistant to chemotherapeutical drugs used in cancer have not been described., Results: Cx reduces angiogenesis in the chick embryonic chorioallantoic membrane assay (CAM), inhibits the growth and microvascular density of the murine TA3-MTXR tumor, reduces microvascular density of tumor metastases, promotes apoptosis and reduces vascular endothelial growth factor (VEGF) production and cell proliferation in the tumor., Conclusion: The antiangiogenic and antitumor Cx effects correlate with its activity on other tumor cell lines, suggesting that Prostaglandins (PGs) and VEGF production are involved. These results open the possibility of using Celecoxib combined with other experimental therapies, ideally aiming to get synergic effects.

Immune-based anti-tumor or anti-angiogenic therapies hold considerable promise for the treatment of cancer. The first approach seeks to activate tumor antigen-specific T lymphocytes while, the second, delays tumor growth by interfering with blood supply. Tumor Associated Antigens are often employed to target tumors with therapeutic drugs, but some are also essential for tumor viability. Survivin (Surv) is a member of the inhibitor of apoptosis protein family that is considered a Tumor Associated Antigen important for cancer cell viability and proliferation. On the other hand, Trypanosoma cruzi (the agent of Chagas' disease) calreticulin (TcCRT) displays remarkable anti-angiogenic properties. Because these molecules are associated with different tumor targets, we reasoned that immunization with a Surv-encoding plasmid (pSurv) and concomitant TcCRT administration should generate a stronger anti-tumor response than application of either treatment separately. To evaluate this possibility, C57BL/6 mice were immunized with pSurv and challenged with an isogenic melanoma cell line that had been pre-incubated with recombinant TcCRT (rTcCRT). Following tumor cell inoculation, mice were injected with additional doses of rTcCRT. For the combined regimen we observed in mice that: i). Tumor growth was impaired, ii). Humoral anti-rTcCRT immunity was induced and, iii). In vitro rTcCRT bound to melanocytes, thereby promoting the incorporation of human C1q and subsequent macrophage phagocytosis of tumor cells. These observations are interpreted to reflect the consequence of the following sequence of events: rTcCRT anti-angiogenic activity leads to stress in tumor cells. Murine CRT is then translocated to the external membrane where, together with rTcCRT, complement C1 is captured, thus promoting tumor phagocytosis. Presentation of the Tumor Associated Antigen Surv induces the adaptive anti-tumor immunity and, independently, mediates anti-endothelial cell immunity leading to an important delay in tumor growth.

Introduction: Antituberculosis-drug resistance surveillance is very important to identify multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis isolates., Objective: To determine the prevalence of resistance in M. tuberculosis strains isolated between 2010 and 2011, and to demonstrate the laboratory performance in the external quality control of drug susceptibility testing., Materials and Methods: A prospective longitudinal study was carried out to determine antituberculosis-drug resistance in 657 M. tuberculosis isolates obtained throughout the country. The nitrate reductase assay was used to detect resistance to isoniazid and rifampin. The proportion method was performed to confirm resistance to these drugs and to further investigate in multidrug-resistant isolates their susceptibility to streptomycin, ethambutol, ofloxacin, kanamycin and capreomycin. Additionally, as part of external quality control, susceptibility was evaluated in two M. tuberculosis strain panels., Results: In 95.69% of the isolates recovered from new tuberculosis cases, and in 72.64 % of isolates from previously treated patients we found susceptibility to isoniazid and rifampicin; multidrug resistance was 1,03 and 10.38%, respectively. We found two extensively resistant isolates. Except for ethambutol and capreomycin, the efficiency of all other drugs was 100% in the external quality control., Conclusion: The study confirmed the low prevalence of M. tuberculosis multidrug-resistant isolates in Cuba. This result was confirmed by the external quality control of drug susceptibility testing.