Anti-allodynic Effect of Mangiferin in Rats with Chronic Post-ischemia Pain: A Model of Complex Regional Pain Syndrome Type I. Garrido-Suárez BB, Garrido G, Castro-Labrada M, Pardo-Ruíz Z, Bellma Menéndez A, Spencer E, et al. Front Pharmacol. 2018 Oct 2;9:1119. DOI: 10.3389/fphar.2018.01119. eCollection 2018.

The present study reproduces chronic post-ischemia pain (CPIP), a model of complex regional pain syndrome type I (CRPS-I), in rats to examine the possible transient and long-term anti-allodynic effect of mangiferin (MG); as well as its potential beneficial interactions with some standard analgesic drugs and sympathetic-mediated vasoconstriction and vasodilator agents during the earlier stage of the pathology. A single dose of MG (50 and 100 mg/kg, p.o.) decreased mechanical allodynia 72 h post-ischemia-reperfusion (I/R). MG 100 mg/kg, i.p. (pre- vs. post-drug) increased von Frey thresholds in a yohimbine and naloxone-sensitive manner. Sub-effective doses of morphine, amitriptyline, prazosin, clonidine and a NO donor, SIN-1, in the presence of MG were found to be significantly anti-allodynic. A long-term anti-allodynic effect at 7 and 13 days post-I/R after repeated oral doses of MG (50 and 100 mg/kg) was also observed. Further, MG decreased spinal and muscle interleukin-1β concentration and restored muscle redox status. These results indicate that MG has a transient and long-term anti-allodynic effect in CPIP rats that appears to be at least partially attributable to the opioid and α₂ adrenergic receptors. Additionally, its anti-inflammatory and antioxidant mechanisms could also be implicated in this effect. The association of MG with sub-effective doses of these drugs enhances the anti-allodynic effect; however, an isobolographic analysis should be performed to define a functional interaction between them. These findings suggest the possible clinical use of MG in the treatment of CRPS-I in both early sympathetically maintained pain and long-term sympathetically independent pain.

“Application of the ultra-micro analytical system (SUMA) technology for the detection of urinary hCG in antidoping control”. Martínez Brito D, Bueno Fis E, Fiallo Fernández T, Torres Castellanos M, Correa Vidal MT, Montes De Oca Porto R. J Immunoassay Immunochem. 2018 Oct 22;39(6):6721–86.

The Ultra Micro Analytical System (SUMA) is an ELISA-based analytical platform, developed and manufactured by the Cuban Immunoassay Center (IC), which is primarily used in clinical medicine applications. In this article, we describe the validation of the UMELISA HCG kits, which are based on SUMA, as a pre-screening procedure for the detection of human Chorionic Gonadotrophin (hCG) in urine for anti-doping purposes. Validation of assay performance parameters showed satisfactory results, in accordance with the criteria established by the World Anti-Doping Agency (WADA): intra-assay repeatability (6.7-9.7%), inter-assay reproducibility (7.8-10.5%), accuracy (91-98%), limit of detection (2.7 IU/L), and linearity. Relative sensitivity and specificity and Predictive Positive and Negative Values were used to evaluate the Efficacy showing a value of 97.6%. A Kappa Index analysis was applied to check agreement with the commercially available, reference assay COBASe411 (Roche), which is often applied in WADA-accredited anti-doping laboratories for measurement of intact (heterodimeric) hCG in urine. UMELISA HCG kits are considered as fit for anti-doping control purposes.

Bone Marrow Transplantation in Patients with Acute Leukemia In Cuba: Results From the Last 30 Years and New Opportunities Through International Collaboration. Carnot Uria J, Hernández Cruz C, Muñío Perurena J, Torres Yribar W, Diego de la Campa J, Del Castillo Carrillo C, et al. J Glob Oncol. 2018 Dec;(4):1–7.

Blood and marrow transplantation (BMT) has been performed in Cuba for over 30 years with limited resources and without international relationships. Researchers from University of Illinois at Chicago and Hermanos Ameijeiras Hospital (HAH) in Havana collaborated on retrospectively analyzing 101 consecutive patients with adult acute leukemia who received BMT at HAH from June 1986 to January 2016. Of these, 82 had acute myeloid leukemia (AML) and 19 had acute lymphoblastic leukemia (ALL). BMT eligibility criteria included prior morphologic complete remission, no severe comorbidities, and age between 16 and 60 years. Patients with an HLA-matched donor received an allogeneic BMT, whereas the others received an autologous BMT. All patients received fresh stem cells from marrow (80%) or mobilized peripheral blood (19%). Of 82 patients with AML, 35 received an allogeneic (AML-allo) and 47 an autologous (AML-auto) BMT. Both groups had comparable median age (37 years) and follow-up of survivors. Overall survival (OS) was 34% in AML-allo and 38% in AML-auto. The transplant-related mortality rate was 40% in AML-allo and 17% in AML-auto, whereas the relapse-related mortality rates were 25% and 40%, respectively. Of the 19 patients with ALL, six received an allogeneic transplant. Of these, transplant-related mortality occurred in one patient and three died after disease relapse (OS, 33%). Of 13 patients who received autologous transplants, transplant-related mortality occurred in three and six died after disease relapse (OS, 31%). To our knowledge, this is the first scientific report on BMT performed in patients with acute leukemia in Cuba. The collaboration between University of Illinois at Chicago and HAH will further develop capacity building in research and implementation of new diagnostic and therapeutic strategies in Cuba.

Cellular Redox Imbalance and Neurochemical Effect in Cognitive-Deficient Old Rats. González-Fraguela ME, Blanco-Lezcano L, Fernández-Verdecia CI, Serrano Sánchez T, Robinson Agramonte MLA, Cardellá Rosales LL. Behav Sci (Basel). 2018 Oct 13;8(10). pii: E93.

The purpose of the present study is to access the linkage between dysregulation of glutamatergic neurotransmission, oxidative metabolism, and serine signaling in age-related cognitive decline. In this work, we evaluated the effect of natural aging in rats on the cognitive abilities for hippocampal-dependent tasks. Oxidative metabolism indicators are glutathione (GSH), malondialdehyde (MDA) concentrations, and cytosolic phospholipase A₂ (PLA₂) activity. In addition, neurotransmitter amino acid (L-Glutamic acid, γ-aminobutyric acid (GABA), DL-Serine and DL-Aspartic acid) concentrations were studied in brain areas such as the frontal cortex (FC) and hippocampus (HPC). The spatial long-term memory revealed significant differences among experimental groups: the aged rats showed an increase in escape latency to the platform associated with a reduction of crossings and spent less time on the target quadrant than young rats. Glutathione levels decreased for analyzed brain areas linked with a significant increase in MDA concentrations and PLA₂ activity in cognitive-deficient old rats. We found glutamate levels only increased in the HPC, whereas a reduced level of serine was found in both regions of interest in cognitive-deficient old rats. We demonstrated that age-related changes in redox metabolism contributed with alterations in synaptic signaling and cognitive impairment.

Diagnostic Value of Anti-Fibrinogen Citrullinated Peptide in Rheumatoid Arthritis. Martínez Tellez G, Torres Rives B, Gómez Morejón JA, Pérez Garay H, Rodríguez AM, Portal Miranda JA. Reumatol Clin. 2018 Dec 26. pii: S1699-258X(18)30258-4.
DOI: 10.1016/j.reuma.2018.11.006. [Epub ahead of print]

Objective To determinate the diagnostic value of an antibody against a citrullinated fibrinogen peptide in Cuban patients with rheumatoid arthritis, using an enzyme immunoassay. Materials and methods A citrullinated peptide of fibrinogen designed by informatics prediction was synthesized and used in an enzyme immunoassay. The participants were 81 patients with early disease, 81 patients with established disease, 58 patients with other rheumatic and inflammatory diseases, and 43 healthy individuals. Anti- citrullinated fibrinogen peptide, anti-mutated citrullinated vimentin, anti second generation citrullinated peptides and rheumatoid factor antibodies were determined by enzyme-linked immunosorbent assay. Results Determination of anti-citrullinated peptide of fibrinogen antibodies by the designed enzyme immunoassay showed the best diagnostic value in early rheumatoid arthritis patients, with the highest value sensitivity (84%), negative predictive value (85%), Youden index (0.73%) and area under the receiver operating curve (0.9192). Specificity (89%) and positive predictive value (88%) were higher than rheumatoid factor, similar to anti- mutated citrullinated vimentin, but lower than second generation anti-citrullinated peptides assay. The positivity of C-reactive protein was associated with the presence of anti- citrullinated fibrinogen peptide antibodies and the titres of these antibodies correlated with clinical activity in early disease. Conclusions The immunoassay designed with a citrullinated fibrinogen peptide has a high diagnostic value and can identify patients with greater clinical activity in early rheumatoid arthritis.

Dose response of Prematurely Condensed Chromosome Rings after gamma irradiation. Guerrero CC, Romero I, Arceo C, González JE, Cortina-Ramírez GE, Garcia O. Int J Radiat Biol. 2019 Jan 7:1–11

Purpose This paper presents a calibration curve for Prematurely Condensed Chromosome Rings (PCC-ring) which are scarce in cytogenetic dosimetry; here we analyzed the behavior of the PCC-ring frequency and PCC index after gamma irradiation in the dose interval from 0 to 20 Gy. Materials and methods PCC-rings were induced in lymphocytes with Calyculin A. A total of 5788 PCC cells in G1, G2/M and M/A stages were analyzed. Results The best fitting curve between the frequency of PCC ring (Y) and the Dose (D) was obtained with the equation Y = (0.0308 ± 0.0012) D. The distribution of rings by cell followed a Poisson distribution. The PCC index was correlated with radiation dose and decreased in a dose dependent manner. Conclusion This PCC-ring dose effect curve can be used in case of high dose accidental overexposure to gamma radiation, allowing a dose assessment in a reliable way in most of the simulated irradiation analyzed.

Internal mammary artery graft failure: Clinical features, management, and long-term outcomes. Núñez-Gil IJ, Alfonso E, Salinas P, Nombela-Franco L, Ramakrishna H, Jimenez-Quevedo P, et al. Indian Heart J. 2018 Dec;70 Suppl 3:S329–S37.

Objective Data on long-term outcomes after internal mammary artery (IMA) coronary graft failure are scarce. Our objective was to describe the clinical characteristics, management, and prognosis after angiographically confirmed IMA graft failure following coronary revascularization. Methods A three-hospital retrospective registry, observational and descriptive, with prospective follow-up of all consecutive cases of IMA graft failure between 2004 and 2014 was conducted. After treatment, clinical and procedural features were compared between those with and without cardiovascular events. Results Fifty-seven patients were included (89% male, mean age: 62 years, at surgery) in the registry. Most patients underwent an IMA angioplasty (percutaneous coronary intervention [PCI], 74%). In nine cases, the PCI failed at the graft level, and seven underwent a native vessel revascularization. Native vessel treatment was performed in 20% of the study subjects, all with stents. Finally, medical management was decided in three cases. Events after treatment for IMA graft failure were frequent (50.8%), during a median follow-up of 7.5 years. Acute presentation (hazard ratio_MACE = 1.35; 95% confidence interval (CI): 1.12-3.00, p < 0.01), age of the patient (hazard ratio_MACE = 1.85, 95% CI: 1.17-2.11, p < 0.01), presence of diabetes mellitus (hazard ratio_MACE = 2.75, 95% CI: 1.13-6.69, p = 0.02), and the management modality used (IMA-simple angioplasty VS IMA-stenting: hazard ratio_MACE = 5.5, 95% CI: 1.40-21.15, p = 0.01) displayed prognostic relevance on multivariate analysis. All-cause mortality occurred in 21.1% and presentation as infarction (hazard ratio_DEATH = 1.05, 95% CI: 1.01-2.17, p = 0.01), age (hazard ratio_DEATH = 9.08, 95% CI: 2.52-32.69, p < 0.01), and left ventricular ejection fraction (hazard ratio_DEATH = 3.68, 95% CI: 1.65-8.18, p < 0.01) were independent predictors of the same. Conclusions In this long-term registry, most patients presented with an acute condition (myocardial infarction, progressive angina) within 12 months after surgery. Acute presentation, age, diabetes mellitus, reduced left ventricular ejection fraction, IMA graft failure segment affected, and the management strategy were related with long-term prognosis.

Intralesional and perilesional application of an epidermal growth factor (Heberprot-P®) in diabetic foot ulcers. Part one. Montequín JF, Bonachea LS, Acosta JB, Peres CV, Gutierres WS, Duarte GA. Angiol Sosud Khir. 2018;24(4):33–42. English, Russian

For 15 years, from 2001, we began to apply Heberprot-P®, an injectable Epidermal Growth Factor (0.75 μg) created in the Center of Biotechnology, in Havana, Cuba. More than 159,000 patients were treated around the world, from 25 countries, with, with only 9-11% high-level amputations. In this paper, we discuss our experience in the treatment of the most complex diabetic foot ulcers cases for the last 15 years.

JM-20, a novel hybrid molecule, protects against rotenone-induced neurotoxicity in experimental model of Parkinson’s disease. Fonseca-Fonseca LA, Wong-Guerra M, Ramírez-Sánchez J, Montano-Peguero Y, Padrón Yaquis AS, Rodríguez AM, et al. Neurosci Lett. 2018 Jan 18;690:29 –35.

Oxidative stress and mitochondrial dysfunction are two pathophysiological factors often associated with the neurodegenerative process involved in Parkinson’s disease (PD). The aim of this study was to investigate the effects of a novel hybrid molecule, named JM-20, in different in vitro and in vivo models of PD induced by rotenone. To perform in vitro studies, SHSY-5Y cells were exposed to rotenone and/or treated with JM-20. To perform in vivo studies male Wistar rats were intoxicated with rotenone (2.5 mg/kg) via intraperitoneal injection and/or treated with JM-20 (40 mg/kg) administered via oral (for 25 days, both treatment). Rats were evaluated for global motor activity by measurement of locomotor activity. In addition, the effects on mortality, general behavior and redox parameters were also investigated. JM-20 protected SHSY-5Y cells against rotenone-induced cytotoxicity, evidenced by a significant diminution of cell death. In in vivo studies, JM-20 prevented rotenone-induced vertical exploration and locomotion frequency reductions, moreover prevented body weight loss and mortality induced by rotenone. It also improved the redox state of rotenone-exposured animals by increasing superoxide dismutase and catalase activities, total tissue-SH levels and decreasing malondialdehyde concentrations. Finally, JM-20 inhibited spontaneous mitochondrial swelling and membrane potential dissipation in isolated rats brain mitochondria. These results demonstrate that JM-20 is a potential neuroprotective agent against rotenone-induced damage in both in vitro and in vivo models, resulting in reduced neuronal oxidative injury and protection of mitochondria from impairment.

Mathematical skills in children with pilocytic astrocytoma. Benavides-Varela S, Lorusso R, Baro V, Denaro L, Estévez-Pérez N, Lucangeli D, ET AL. Acta Neurochir (Wien). 2019 Jan;161(1):161–9.

Background Pediatric patients with circumscribed cerebellar pilocytic astrocytoma (PA) tumors generally perform within the normal range on neuropsychological tests after a complete tumor resection. The outcome in academically relevant abilities such as mathematics, which in adults involve some cerebellar functions, is however much less understood. The aim of this study is to retrospectively investigate the neuroplasticity of mathematical skills and associated cognitive functions following cerebellar resection of PA in pediatric patients. Methods Twenty-two children (mean age = 11.2 + 1.8), including 11 PA patients (females = 6) and 11 healthy controls (females = 6), were administered a battery of mathematical (MaT) and neuropsychological tests. Single-case statistical analyses were carried out (Crawford’s t) as well as between-group comparisons (Wilcoxon test). Spearman correlations between MaT and neuropsychological tests were calculated. Results Thirty-six percent of the patients showed difficulties in some mathematical tasks, 50% of them within a broader cognitive deficit. Verbal working memory was associated with MaT performance both in patients and controls while, crucially, visuospatial memory, and visual-motor integration were associated with MaT in patients only. Among patients, MaT correlated negatively with tumor size and positively with the interval surgery test. Conclusions The results evince an overall recovery of mathematical abilities despite PA in the majority of patients. This functional reestablishment is supported by visuospatial and visuomotor integration functions that contribute to set up emerging mathematical skills in these patients. Higher levels of compensation are found in more developed tumors as compared to smaller ones.

Mycobacterium “habana” TMC 5135 as a vaccine candidate against tuberculosis: In vitro studies. Martínez JVS, Hernández IVS, Echemendía M, Rodríguez H, Yglesias A, Díaz A. Int J Mycobacteriol. 2018 Oct–Dec;7(4):346.

Background Tuberculosis (TB) is one of the biggest problems of global health, at present. Bacillus–Calmette–Guérin is the only vaccine available against this disease. It protects only against the severe forms of TB in the childhood, which is a challenge in the search of new vaccine candidates. Taking into account the protective history of Mycobacterium “habana” against experimental TB, we proposed to provide the elements that support the use of M. “habana” TMC 5135 as a vaccine candidate against TB by infection studies in murine macrophages cell cultures. Methods The production of microbicidal compounds dependent on oxygen metabolism as nitric oxide and hydrogen peroxide by murine peritoneal macrophages was detected. The invasive and toxigenic capacity of M. “habana” to infect this cell type was also evaluated through the quantification of intracellular alive bacillus and 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay, respectively. Results The results suggest that M. “habana” TMC 5135 is able to persist into peritoneal macrophages, to resist the effectors mechanisms of respiratory burst, and to keep the viability of the target cell. The demonstration of these effector mechanisms and the survival capacity of M. “habana” in this niche are relevant aspects of this research assuring the continuity of this candidate to next phases of preclinical development. Conclusion The present investigation contributes to the characterization of the infection by this mycobacteria in its main target cells of innate immunity and it suggest future investigations to evaluate the activation of effector mechanisms of the innate immunity against this candidate.

Multilocus sequence typing of Treponema pallidum subsp. pallidum in Cuba from 2012 to 2017. Grillová L, Noda AA, Lienhard R, Blanco O, Rodríguez I, Šmajs D. J Infect Dis. 2018 Oct 16. DOI: 10.1093/infdis/jiy604. [Epub ahead of print]

Background The increased prevalence of syphilis in Cuba prompted us to map the circulating Treponema pallidum subsp. pallidum (TPA) allelic profiles in this geographic region. Methods Samples were collected from 2012-2017, from 83 male patients with ulcers or skin lesions, and were examined using MLST. Additionally, we analyzed the 23S rDNA and 16S rDNA regions for the presence of possible mutations leading to macrolide and tetracycline resistance. Results Among 94% of fully typed strains, we found seven different allelic profiles, from which four had not been previously described. More than 87% of patients were infected with the TPA SS14-like group and only 8.2% with the TPA Nichols-like group. As in other countries, the 1.3.1 allelic profile (i.e., the SS14-like profile) was the most common profile. In addition, one of the newly described allelic profiles represents TPA strains that arose by recombination events between members of different TPA subgroups. More than 90% of the patients were infected with treponemes harboring the A2058G mutation. However, we did not find any potential tetracycline resistant TPA mutations. Conclusions Our study invites the Public Health authorities in Cuba to use tetracycline antibiotics for treatment of syphilis, in penicillin allergic patients, instead of macrolides.

Relation of Structural and Functional Changes in Auditory and Visual Pathways after Temporal Lobe Epilepsy Surgery. Báez-Martín MM, Morales-Chacón LM, García-Maeso I, Estupiñán-Díaz B, García-Navarro ME, Pérez Téllez Y, et al. Behav Sci (Basel). 2018 Oct 12;8(10). pii: E92. DOI: 10.3390/bs8100092

Auditory and visual pathways may be affected as a consequence of temporal lobe epilepsy surgery because of their anatomical relationships with this structure. The purpose of this paper is to correlate the results of the auditory and visual evoked responses with the parameters of tractography of the visual pathway, and with the state of connectivity between respective thalamic nuclei and primary cortices in both systems after the surgical resection of the epileptogenic zone in drug-resistant epileptic patients. Tractography of visual pathway and anatomical connectivity of auditory and visual thalamus-cortical radiations were evaluated in a sample of eight patients. In general, there was a positive relationship of middle latency response (MLR) latency and length of resection, while a negative correlation was found between MLR latency and the anatomical connection strength and anatomical connection probability of the auditory radiations. In the visual pathway, significant differences between sides were found with respect to the number and length of tracts, which was lower in the operated one. Anatomical connectivity variables and perimetry (visual field defect index) were particularly correlated with the latency of P100 wave which was obtained by quadrant stimulation. These results demonstrate an indirect functional modification of the auditory pathway and a direct traumatic lesion of the visual pathway after anterior temporal lobectomy in patients with drug resistant epilepsy.

Self-association and folding in membrane determine the mode of action of peptides from the lytic segment of sticholysins. Ros U, Carretero GPB, Paulino J, Crusca E Jr, Pazos F, Cilli EM, et al. Biochimie. 2018 Oct 13;156:109–17.

Sticholysin I and II (Sts: St I and St II) are proteins of biomedical interest that form pores upon the insertion of their N-terminus in the plasma membrane. Peptides spanning the N-terminal residues of StI (StI_1-31) or StII (StII_1-30) can mimic the permeabilizing ability of these toxins, emerging as candidates to rationalize their potential biomedical applications. These peptides have different activities that correlate with their hydrophobicity. However, it is not clear how this property contributes to peptide folding in solution or upon binding to membranes. Here we compared the conformational properties of these peptides and shorter versions lacking the hydrophobic segment 1-11 of StI (StI_12-31) or 1-10 of StII (StII_11-30). Folding of peptides was assessed in solution and in membrane mimetic systems and related with their ability to bind to membranes and to permeabilize lipid vesicles. Our results suggest that the differences in activity among peptides could be ascribed to their different folding propensity and different membrane binding properties. In solution, StII_1-30 tends to acquire α-helical conformation coexisting with self-associated structures, while StI_1-31 remains structureless. Both peptides fold as α-helix in membrane; but StII_1-30 also self-associates in the lipid environment, a process that is favored by its higher affinity for membrane. We stress the contribution of the non-polar/polar balance of the 1-10 amino acid sequence of the peptides as a determining factor for different self-association capabilities. Such difference in hydrophobicity seems to determine the molecular path of peptides folding upon binding to membranes, with an impact in their permeabilizing activity. This study contributes to a better understanding of the molecular mechanisms underlying the permeabilizing activity of Sts N-terminal derived peptides, with connotation for the exploitation of these small molecules as alternative of the full-length toxins in clinical settings.

Spatio-temporal distribution of vertically transmitted dengue viruses by Aedes aegypti (Diptera: Culicidae) from Arroyo Naranjo, Havana, Cuba. Gutiérrez-Bugallo G, Rodríguez-Roche R, Díaz G, Pérez M, Mendizábal ME, Peraza I, et al. Trop Med Int Health. 2018 Dec;23(12):1342–9.

Objective To study the distribution of vertical transmission of dengue viruses in field-collected Aedes aegypti larvae in the municipality of Arroyo Naranjo in Havana, Cuba. Methods Ae. aegypti larvae and pupae were collected monthly between September 2013 and July 2014 in the seven Municipal Health Areas of Arroyo Naranjo. Pools formed of 30-55 larvae were examined through PCR and sequencing to detect the presence of each serotype. Results We analyzed 111 pools of larvae and pupae (4102 individuals) of which 37 tested positive for at least one DENV. More than one DENV type was observed in 10 of the 37 positive pools. Infected pools were detected every month, except in January, suggesting a sustained circulation of DENV in the vector populations. DENV-1 and DENV-3 were the most frequent and dispersed, though all four DENV types were detected. Nucleotide sequencing from positive pools confirmed RT-PCR results for DENV-1 (genotype V), DENV-3 (genotype III) and DENV-4 (genotype II). DENV-2 was detected by RT-PCR but could not be confirmed by nucleotide sequencing. Conclusion Our study of the distribution of natural vertical transmission of dengue virus types highlights extrinsic virus activity patterns in the area and could be used as a new surveillance tool.

The Effects of Dietary Flaxseed on Cardiac Arrhythmias and Claudication in Patients with Peripheral Arterial Disease. Rodríguez Leyva D, Rodríguez-Portelles A, Weighell W, Guzmán R, Maddaford TG, Pierce GN. Can J Physiol Pharmacol. 2018 Oct 11. DOI: 10.1139/cjpp-2018-0280. [Epub ahead of print]

Patients with peripheral artery disease (PAD) are at increased risk for cardiovascular events and higher susceptibility for cardiac arrhythmias may be involved. The objectives of this double blinded, randomized controlled FLAX-PAD trial were to determine whether daily consumption of a diet supplemented with 30g of milled flaxseed (or placebo) over one year by PAD patients has effects on the prevalence of cardiac arrhythmias and exercise capacity. Cardiac arrhythmias were assessed on a cardiac stress test and at rest. At baseline, the PAD patients had a high incidence of cardiac arrhythmias (48% in the flaxseed group and 32% in the placebo group). After 1 year, the presence of cardiac arrhythmias in the flaxseed group decreased by 2% and increased by 12% in the placebo group (P>0.05). Electrocardiographic variables (P, PR, QRS, QT, QTc) did not change in either group during the trial. Patients from both groups improved initial and absolute claudication distances but the intergroup difference was also not statistically significant. In summary, the prevalence of cardiac arrhythmias and physical capacity trended in a positive direction for patients ingesting flaxseed but either a larger sample size or a longer intervention with flaxseed may be required to show statistically significant differences.

The effects of metabolic status on non-alcoholic fatty liver disease-related outcomes, beyond the presence of obesity. Ampuero J, Aller R, Gallego-Durán R, Banales JM, Crespo J, García-Monzón C,et al. Aliment Pharmacol Ther. 2018 Dec;48(11–2):1260–70.

Background Metabolically healthy obesity (MHO) shows a reduced risk compared with obese patients with adverse metabolic conditions. Lean people suffering some metabolic derangements also have non-alcoholic fatty liver disease (NAFLD)-related outcomes compared with non-obese subjects with a few metabolic risks. Aim To define the impact of the metabolic status on the NAFLD-related outcomes, beyond the presence of obesity. Methods We designed a multicentre cross-sectional study, including 1058 biopsy-proven NAFLD patients. Metabolically healthy status was strictly defined by the lack of metabolic risk factors (diabetes mellitus, low HDL, hypertriglyceridemia, arterial hypertension). Non-alcoholic steatohepatitis (NASH) and significant fibrosis (F2-F4) were identified by liver biopsy. Chronic kidney disease epidemiology collaboration equation was calculated for kidney function and the atherogenic index of plasma (AIP) for cardiovascular risk. Results Metabolically healthy (OR 1.88; P = 0.050) and unhealthy obesity (OR 3.47: P < 0.0001), and unhealthy non-obesity (OR 3.70; P < 0.0001) were independently associated with NASH together with homeostatic model assessment (HOMA), ALT, and platelets. Significant fibrosis was more frequently observed in the presence of adverse metabolic conditions in obese (OR 3.89; P = 0.003) and non-obese patients (OR 3.92; P = 0.002), and independently associated with platelets, albumin, ALT, HOMA, and age. The number of metabolic factors determined the risk of NASH and significant fibrosis. Glomerular filtration rate was lower in unhealthy (91.7 ± 18) than healthy metabolism (95.6 ± 17) (P = 0.007). AIP was higher in adverse metabolic conditions (P = 0.0001). Metabolically unhealthy non-obesity showed higher liver damage (NASH 55.8% vs 42.4%; P < 0.05; significant fibrosis 31.7% vs 11.4%; P < 0.0001) and cardiovascular risk (P < 0.0001) than healthy obesity. Conclusions Metabolic unhealthy status showed a greater impact on NASH, significant fibrosis, kidney dysfunction, and atherogenic profile than obesity. However, metabolically healthy obesity was not a full healthy condition. We should focus our messages especially on patients with adverse metabolic conditions.

Treatment of refractory paediatric giardiasis using secnidazole plus albendazole: a case series. Escobedo AA, Almirall P, Chirino E, Pacheco F, Duque A, Avila i. Infez Med. 2018 Dec 1;26(4):379–84.

Giardia lamblia, the aetiological agent of human giardiasis, is a frequently identified protozoan infection of the upper small intestine. It mainly affects children and has a wide range of clinical manifestations, from asymptomatic carriage to acute or chronic diarrhoea with dehydration, abdominal pain, nausea, vomiting, excessive flatulence and weight loss. Standard treatment for giardiasis is commonly with 5-nitroimidazole (5-NI) compounds, or nitazoxanide; however, some individuals experience treatment failure. For such patients, a combination of two or more drugs may be a viable approach. We report our experience with 11 paediatric patients with drug-refractory giardiasis, for whom therapy with a combination of secnidazole (SNZ) (30 mg/kg/day, divided into 2 doses, for 3 days) and albendazole (ABZ) (400 mg daily for 5 days) resulted in cure for 9 of the 11 (82%) patients. This combination of drugs was well tolerated; only mild, transient, and self-limited side effects were reported and these did not require discontinuation of treatment. These results support the use of SNZ plus ABZ as an alternative treatment for paediatric patients with giardiasis who have failed conventional treatments. Further research is needed to establish the safety of this combination and how it compares to other combination strategies.