Recent Submissions

  • Factors associated with the severity of pruritus in patients with terminal chronic kidney disease undergoing hemodialysis in Lima, Peru

    Kossuth-Cabrejos, Stefano; Gavino-Gutiérrez, Arquímedes M.; Silva-Caso, Wilmer (Page Press Publications, 2020-01-01)
    The objective of the study is to analyze the factors associated with the severity of pruritus in patients with terminal chronic kidney disease undergoing hemodialysis. The methodology used is based on a cross-sectional study in patients receiving hemodialysis at the Centro Nacional de Salud Renal. Severe pruritus was defined as a score on the visual analogue scale greater than or equal to 7, and the strength of association with the possible risk factors was assessed by calculating prevalence ratios. Regarding the results, 264 patients were included, 59.9% were male, with a mean time on hemodialysis of 10.26 ± 7.14 years. 75% experienced pruritus, of this group, 1 in 3 presented severe pruritus. Hyperphosphatemia and the use of antihistamines were associated with a higher prevalence of severe pruritus (RP 1.71, 95% CI 1.09-267 and RP 2.39, 95% CI 1.51-3.75, respectively). The positive serology for Hepatitis C Virus was described as a protective factor for presenting severe pruritus (RP 0.55, 95% CI 0.33 - 0.89). In conclusion, severe uremic pruritus is a frequent problem in patients with chronic terminal kidney disease who have hyperphosphatemia and treatment with antihistamines independently of the time they have been on hemodialysis.
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  • Prevalence of Diabetes Mellitus and Its Associated Unfavorable Outcomes in Patients With Acute Respiratory Syndromes Due to Coronaviruses Infection: A Systematic Review and Meta-Analysis

    Pinedo-Torres, Isabel; Flores-Fernández, Magaly; Yovera-Aldana, Marlon; Gutierrez-Ortiz, Claudia; Zegarra-Lizana, Paolo; Intimayta-Escalante, Claudio; Moran-Mariños, Cristian; Alva-Diaz, Carlos; Pacheco-Barrios, Kevin (SAGE Publications Ltd, 2020-01-01)
    Introduction: Only 3 types of coronavirus cause aggressive respiratory disease in humans (MERS-Cov, SARS-Cov-1, and SARS-Cov-2). It has been reported higher infection rates and severe manifestations (ICU admission, need for mechanical ventilation, and death) in patients with comorbidities such as diabetes mellitus (DM). For this reason, this study aimed to determine the prevalence of diabetes comorbidity and its associated unfavorable health outcomes in patients with acute respiratory syndromes for coronavirus disease according to virus types. Methods: Systematic review of literature in Pubmed/Medline, Scopus, Web of Science, Cochrane, and Scielo until April of 2020. We included cohort and cross-sectional studies with no restriction by language or geographical zone. The selection and extraction were undertaken by 2 reviewers, independently. The study quality was evaluated with Loney’s instrument and data were synthesized by random effects model meta-analysis. The heterogeneity was quantified using an I2 statistic. Funnel plot, Egger, and Begg tests were used to evaluate publication biases, and subgroups and sensitivity analyses were performed. Finally, we used the GRADE approach to assess the evidence certainty (PROSPERO: CRD42020178049). Results: We conducted the pooled analysis of 28 studies (n = 5960). The prevalence analysis according to virus type were 451.9 diabetes cases per 1000 infected patients (95% CI: 356.74-548.78; I2 = 89.71%) in MERS-Cov; 90.38 per 1000 (95% CI: 67.17-118.38) in SARS-Cov-1; and 100.42 per 1000 (95% CI: 77.85, 125.26 I2 = 67.94%) in SARS-Cov-2. The mortality rate were 36%, 6%, 10% and for MERS-Cov, SARS-Cov-1, and SARS-Cov-2, respectively. Due to the high risk of bias (75% of studies had very low quality), high heterogeneity (I2 higher than 60%), and publication bias (for MERS-Cov studies), we down rate the certainty to very low. Conclusion: The prevalence of DM in patients with acute respiratory syndrome due to coronaviruses is high, predominantly with MERS-Cov infection. The unfavorable health outcomes are frequent in this subset of patients. Well-powered and population-based studies are needed, including detailed DM clinical profile (such as glycemic control, DM complications, and treatment regimens), comorbidities, and SARS-Cov-2 evolution to reevaluate the worldwide prevalence of this comorbidity and to typify clinical phenotypes with differential risk within the subpopulation of DM patients.
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  • Physical activity levels by glycemia status: A population-based cross-sectional study in Peru

    Ganoza-Calero, Antonelhla M.; Cuadros-Torres, Milagros; Bernabé-Ortiz, Antonio (Elsevier Ltd, 2021-04-01)
    Objective: To assess whether the prevalence of low physical activity levels and time spent watching TV differ depending on glycemia status. Methods: A secondary analysis using data from a population-based study was conducted. Two were the outcomes: physical activity levels, derived from the International Physical Activity Questionnaire, and sitting time watching TV. The exposure was glycemia status, defined based on results of the oral glucose tolerance tests (OGTT): euglycemia, dysglycemia, and T2DM. The T2DM group was further split into: aware and unaware of T2DM diagnosis. Prevalence ratios (PR) and 95% CI were reported using Poisson regression models. Results: Data of 1607 individuals, mean age 48.2 (SD: 10.6) years, 809 (50.3%) females, were analyzed. Dysglycemia and T2DM was present in 16.9% (95% CI: 15.1%–18.8%) and 11.0% (95% CI: 9.5%–12.6%) of participants, respectively. A total of 605 (37.6%; 95% CI: 35.2%–39.9%) participants had low levels of physical activity and 1019 (63.3%; 95% CI: 60.9%–65.7%) subjects spent ≥2 h per day sitting watching TV. In multivariable model, there was no significant association between glycemia status and physical activity levels (PR = 1.14; 95% CI: 0.95–1.36). Similar result was found between glycemia status and sitting time watching TV. However, those aware of T2DM diagnosis were more likely to have low levels of physical activity (PR = 1.31; 95% CI: 1.06–1.61) compared to the euglycemia group. Conclusions: We found a no relationship between glycemia status and physical activity level or sitting time watching TV, pointing out similar levels of physical (in)activity among those with euglycemia, dysglycemia and T2DM. Individuals aware of having T2DM were 30% more likely to have low physical activity levels compared to the euglycemic group. There is a need to increase physical activity levels among T2DM individuals.
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  • Carvacrol: An in silico approach of a candidate drug on HER2, PI3Kα, mTOR, HER-α, PR, and EGFR receptors in the breast cancer

    Herrera-Calderon, Oscar; Yepes-Pérez, Andres F.; Quintero-Saumeth, Jorge; Rojas-Armas, Juan Pedro; Palomino-Pacheco, Miriam; Ortiz-Sánchez, José Manuel; Cieza-Macedo, Edwin César; Arroyo-Acevedo, Jorge Luis; Figueroa-Salvador, Linder; Peña-Rojas, Gilmar; Andía-Ayme, Vidalina (Hindawi Limited, 2020-01-01)
    Carvacrol is a phenol monoterpene found in aromatic plants specially in Lamiaceae family, which has been evaluated in an experimental model of breast cancer. However, any proposed mechanism based on its antitumor effect has not been reported. In our previous study, carvacrol showed a protective effect on 7,12-dimethylbenz[α]anthracene- (DMBA-) induced breast cancer in female rats. The main objective in this research was to evaluate by using in silico study the carvacrol on HER2, PI3Kα, mTOR, hERα, PR, and EGFR receptors involved in breast cancer progression by docking analysis, molecular dynamic, and drug-likeness evaluation. A multilevel computational study to evaluate the antitumor potential of carvacrol focusing on the main targets involved in the breast cancer was carried out. The in silico study starts with protein-ligand docking of carvacrol followed by ligand pathway calculations, molecular dynamic simulations, and molecular mechanics energies combined with the Poisson–Boltzmann (MM/PBSA) calculation of the free energy of binding for carvacrol. As result, the in silico study led to the identification of carvacrol with strong binding affinity on mTOR receptor. Additionally, in silico drug-likeness index for carvacrol showed a good predicted therapeutic profile of druggability. Our findings suggest that mTOR signaling pathway could be responsible for its preventive effect in the breast cancer.
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  • Social networks and condomless intercourse with female partners among male sex workers in the Dominican Republic

    Saiyed, Faiez K.; Segura, Eddy R.; Tan, Diane; Clark, Jesse L.; Lake, Jordan E.; Holloway, Ian W. (SAGE Publications Ltd, 2021-02-01)
    Male sex workers (MSW) in the Dominican Republic (DR) have multiple sexual partners, including personal and client-relationships, and are disproportionately affected by human immunodeficiency virus (HIV). We examined the prevalence of condomless anal and/or vaginal intercourse (CI) among MSW in the DR as a function of social network factors. Self-report surveys and social network interviews were administered to MSW recruited through venue-based sampling (N = 220). A generalized linear model was used to complete a Poisson Regression model and identify variables significantly associated with the outcome of interest. CI was more common with female (28.3%) than with male partners (4.9%). Factors associated with CI with the last female partner included older age of MSW, CI with the last male partner, having a stable female partner (a consistent or main partner), and having ≥1 family member in the participants’ social network. Partner and social network characteristics associated with CI among MSW suggest the utility of dyadic and network interventions to reduce HIV risk.
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  • Cultural adaptation and validation of SATAQ-4 “Sociocultural attitudes towards appearance questionnaire-4” for peruvian population

    Zevallos-Delzo, Carolina; Maguiña, Jorge L.; Catacora, Manuel; Mayta-Tristán, Percy (Sociedad de Neurologia Psiquiatria y Neurocirugia, 2020-03-01)
    Introduction: Eating disorders (anorexia and bulimia) have been increasing worldwide and nationally. Prior to the development of this disorder, adolescents' present body dissatisfaction, whose study through the ¨Tripartite Influence Model¨ gives us three main pressures: Pressure from parents, media and peers. Factors that are studied through SATAQ-4. We conduct a study to validate the Peruvian version of SATAQ-4 "Sociocultural Attitudes Toward Appearance Questionnaire-4". Methods: A cross-sectional study was carried out in 2015. It was started by culturally adapting the test. Subsequently, validity was determined through the validity of the construct, and reliability through internal consistency assessment and intra-observer reliability (test-retest). Results: We obtained a culturally adapted instrument which presented a mean greater than 3 in the Delphi method, an intraclass correlation equal to 0.83 and an internal consistency (Cronbach alpha) of 0.90. The confirmatory factor analysis supported the original five-factor structure and the convergent validity analysis (r Pearson) when compared with BSQ a correlation of 0.70. Conclusions: The instrument adequately measures the construct for which it was created and can be applied in the Peruvian university environment.
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  • Ameliorative Effect of the Oral Administration of Chuquiraga spinosa in a Murine Model of Breast Cancer Induced with 7,12-Dimethylbenz[a]anthracene (DMBA)

    Arroyo-Acevedo, Jorge Luis; Herrera-Calderon, Oscar; Tinco-Jayo, Johnny Aldo; Rojas-Armas, Juan Pedro; Rauf, Abdur; Hañari-Quispe, Renán; Figueroa-Salvador, Linder; Fernández-Guzmán, Victor; Yuli-Posadas, Ricardo Ángel (EManuscript Technologies, 2020-05-01)
    Objective: To determine the ameliorative effect of the ethanolic extract of Chuquiraga spinosa (ChS) on 7,12-Dimethylbenz[a]anthracene (DMBA)-induced breast cancer in rats. Methods: 36 female Holztman rats were divided into 6 groups. I) The negative control group received physiological saline (PS). II) ChS-200 group received 200 mg/kg of ChS. III) DMBA group was induced with DMBA (20 mg/Kg) dissolved in PS and administrated orally for 15 weeks. IV) DMBA + ChS-50 group, V) DMBA + ChS-250 group, and VI) DMBA + ChS-500 group, which received the extract orally for 15 weeks after DMBA induction. All data were expressed as mean and standard deviation. One-way analysis of variance (ANOVA) followed by Dunnet test was carried out to compare the mean value of different groups Histopathological analysis was evaluated by using Image J software. Results: Hematology showed that the triglyceride level was significantly lowered (P< 0.01) and high-density lipoprotein (HDL) level was significantly increased (P <0.01) in groups III, IV and V. Also, ChS extract significantly lowered the C reactive protein (CRP) level (P <0.01) and malondialdehyde level (P<0.05). There was a significant decrease in the frequency of DMBA-induced micronucleated polychromatic erythrocyte (P<0.01). Conclusions: Chuquiraga spinosa showed an ameliorative effect on DMBA-induced breast cancer in rats as well as antioxidant, antitumor and antigenotoxic properties.
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  • Association between Maternal Depressive Symptoms with Overweight/Obesity among Children Aged 0-5 Years According to the 2016 Demographic and Family Health Survey

    Echevarría-Castro, Nataly; Matayoshi-Pérez, Andrea; Alvarado, Germán F. (Mary Ann Liebert Inc., 2020-07-01)
    Background: Overweight and obesity among children under the age of 5 have become a public health problem. The worldwide prevalence is 4.9% and 6.0%, whereas in Peru it is 7.4% and 1.9%, respectively. The causes of these problems are multifactorial and must be studied to prevent the multiple consequences on children's health. Methods: Secondary data analysis of the 2016 Demographic and Family Health Survey (DHS). The sample size was 7935 children and their mothers. The dependent variable was childhood overweight/obesity, measured according to the Z-score of the BMI >2 standard deviation (SD), while the main independent variable consisted of the maternal depressive symptoms (DS) (Patient Health Questionnaire-9 score >10 points). The software STATA/MP 14.0 was used for statistical analysis. Results: The prevalence of overweight/obesity among children aged 0-5 years was 4.5% and the prevalence of moderate and severe maternal DS was 7.1%. No maternal depressive symptoms were found to be associated with the outcome [adjusted PR = 1.36 95% confidence interval (CI) = 0.59-3.09 p = 0.47]. An association was found between socioeconomic status (SES) Q3 (adjusted PR = 3.86 95% CI = 1.9-7.6 p < 0.0001), Q4 (adjusted PR = 5.53 95% CI = 2.76-11.1 p < 0.0001), Q5 (adjusted PR = 6.9 95% CI = 3.24-14.7 p = < 0.0001), maternal BMI (adjusted PR = 1.06 95% CI = 1.03-1.08 p < 0.0001), and cesarean delivery (adjusted PR = 1.42 95% CI = 1.01-1.99 p = 0.042). Conclusions: No association was found between maternal depressive symptoms and overweight/obesity among children aged 0-5 years. The upper SES quintiles, maternal BMI, and cesarean delivery were associated with the outcome.
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  • Endoscopic ultrasound-guided injection of coils for the treatment of refractory post-ERCP bleeding

    Guzmán-Calderón, Edson; Ruiz, Francisco; Casellas, Juan Antonio; Martinez-Sempere, Juan; Medina-Prado, Lucía; Aparicio, Jose R. (Georg Thieme Verlag, 2020-08-01)
    No presenta resumen.
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  • Association of statin use and clinical outcomes in heart failure patients: A systematic review and meta-analysis

    Bielecka-Dabrowa, Agata; Bytyçi, Ibadete; Von Haehling, Stephan; Anker, Stefan; Jozwiak, Jacek; Rysz, Jacek; Hernandez, Adrian V.; Bajraktari, Gani; Mikhalidis, Dimitri P.; Banach, Maciej (BioMed Central Ltd, 2019-10-31)
    Background The role of statins in patients with heart failure (HF) of different levels of left ventricular ejection fraction (LVEF) remains unclear especially in the light of the absence of prospective data from randomized controlled trials (RCTs) in non-ischemic HF, and taking into account potential statins’ prosarcopenic effects. We assessed the association of statin use with clinical outcomes in patients with HF. Methods We searched PubMed, EMBASE, Scopus, Google Scholar and Cochrane Central until August 2018 for RCTs and prospective cohorts comparing clinical outcomes with statin vs non-statin use in patients with HF at different LVEF levels. We followed the guidelines of the 2009 PRISMA statement for reporting and applied independent extraction by multiple observers. Meta-analyses of hazard ratios (HRs) of effects of statins on clinical outcomes used generic inverse variance method and random model effects. Clinical outcomes were all-cause mortality, cardiovascular (CV) mortality and CV hospitalization. Results Finally we included 17 studies (n = 88,100; 2 RCTs and 15 cohorts) comparing statin vs non-statin users (mean follow-up 36 months). Compared with non-statin use, statin use was associated with lower risk of all-cause mortality (HR 0.77, 95% confidence interval [CI], 0.72–0.83, P < 0.0001, I2 = 63%), CV mortality (HR 0.82, 95% CI: 0.76–0.88, P < 0.0001, I2 = 63%), and CV hospitalization (HR 0.78, 95% CI: 0.69–0.89, P = 0.0003, I2 = 36%). All-cause mortality was reduced on statin therapy in HF with both EF < 40% and ≥ 40% (HR: 0.77, 95% Cl: 0.68–0.86, P < 0.00001, and HR 0.75, 95% CI: 0.69–0.82, P < 0.00001, respectively). Similarly, CV mortality (HR 0.86, 95% CI: 0.79–0.93, P = 0.0003, and HR 0.83, 95% CI: 0.77–0.90, P < 0.00001, respectively), and CV hospitalizations (HR 0.80 95% CI: 0.64–0.99, P = 0.04 and HR 0.76 95% CI: 0.61–0.93, P = 0.009, respectively) were reduced in these EF subgroups. Significant effects on all clinical outcomes were also found in cohort studies’ analyses; the effect was also larger and significant for lipophilic than hydrophilic statins. Conclusions In conclusion, statins may have a beneficial effect on CV outcomes irrespective of HF etiology and LVEF level. Lipophilic statins seem to be much more favorable for patients with heart failure.
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  • Pregnancy-Induced Hemophagocytic Lymphohistiocytosis: A Case Report

    Sánchez-Ato, Luis A.; Cuestas-Quiroz, Flavia A.; Agurto-Saldaña, Carla; Estela-Ayamamani, David (Springer, 2020-10-01)
    No presenta presenta resumen.
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  • Alsinol, an arylamino alcohol derivative active against Plasmodium, Babesia, Trypanosoma, and Leishmania: past and new outcomes

    Arias, Maria H.; Quiliano, Miguel; Bourgeade-Delmas, Sandra; Fabing, Isabelle; Chantal, Isabelle; Berthier, David; Minet, Cécile; Eparvier, Veronique; Sorres, Jonathan; Stien, Didier; Galiano, Silvia; Aldana, Ignacio; Valentin, Alexis; Garavito, Giovanny; Deharo, Eric (Springer Science and Business Media Deutschland GmbH, 2020-10-01)
    Malaria, babesiosis, trypanosomosis, and leishmaniasis are some of the most life-threatening parasites, but the range of drugs to treat them is limited. An effective, safe, and low-cost drug with a large activity spectrum is urgently needed. For this purpose, an aryl amino alcohol derivative called Alsinol was resynthesized, screened in silico, and tested against Plasmodium, Babesia, Trypanosoma, and Leishmania. In silico Alsinol follows the Lipinski and Ghose rules. In vitro it had schizontocidal activity against Plasmodium falciparum and was able to inhibit gametocytogenesis; it was particularly active against late gametocytes. In malaria-infected mice, it showed a dose-dependent activity similar to chloroquine. It demonstrated a similar level of activity to reference compounds against Babesia divergens, and against promastigotes, and amastigotes stages of Leishmania in vitro. It inhibited the in vitro growth of two African animal strains of Trypanosoma but was ineffective in vivo in our experimental conditions. It showed moderate toxicity in J774A1 and Vero cell models. The study demonstrated that Alsinol has a large spectrum of activity and is potentially affordable to produce. Nevertheless, challenges remain in the process of scaling up synthesis, creating a suitable clinical formulation, and determining the safety margin in preclinical models.
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  • Facial reconstruction according to aesthetic units

    Nunez Castaneda, José; Chang Grozo, Silvana (Wolters Kluwer Medknow Publications, 2020-10-01)
    Context: The facial subunit principle organizes the facial skin into subunits. Facial reconstruction for skin cancer based on aesthetic units consists of replacing the entire subunit when a large part of a subunit has been removed. Aims: To determine the prevalence of facial skin cancer, their location by facial aesthetic units, and the type of facial reconstruction used in each of them. Settings and Design: An observational cross-sectional study was conducted at the Head and Neck Surgery Service of a general hospital between 2017 and 2018. Materials and Methods: A population census was conducted during this period. Statistical Analysis Used: The categorical variables were expressed as frequencies (percentages). Continuous variables were described as the means and standard deviations or medians and interquartile ranges. Results: The most common skin cancer was basal cell skin cancer, followed by epithelial skin cancer and, at last, melanoma. In general, the most frequent localization of these cancers was the nose. Conclusions: In spite of primary closure being the most common form of reconstruction, a considerable number of patients required facial reconstruction based on aesthetic facial units, with satisfying results.
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  • Safety and efficacy of drug eluting stents vs bare metal stents in patients with atrial fibrillation: A systematic review and meta-analysis

    Sambola, Antonia; Rello, Pau; Soriano, Toni; Bhatt, Deepak L.; Pasupuleti, Vinay; Cannon, Christopher P.; Gibson, C. Michael; Dewilde, Willem J.M.; Lip, Gregory Y.H.; Peterson, Eric D.; Airaksinen, K. E.Juhani; Kiviniemi, Tuomas; Fauchier, Laurent; Räber, Lorenz; Ruiz-Nodar, Juan M.; Banach, Maciej; Bueno, Héctor; Hernandez, Adrian V. (Elsevier Ltd, 2020-11-01)
    Objective: A systematic review and meta-analysis was performed to evaluate the safety and efficacy of drug-eluting stents (DES) vs bare-metal stents (BMS) in atrial fibrillation (AF) patients. Methods: We systematically searched 5 engines until May 2019 for cohort studies and randomized controlled trials (RCTs). Primary outcomes were major bleeding and major adverse cardiac events (MACE) including cardiac death, myocardial infarction, target vessel revascularization (TVR) or stent thrombosis. Effects of inverse variance random meta-analyses were described with relative risks (RR) and their 95% confidence intervals (CI). We also stratified analyses by type (triple [TAT] vs dual [DAT]) and duration (short-vs long-term) of antithrombotic therapy. Results: Ten studies (3 RCTs; 7 cohorts) including 10,353 patients (DES: 59.6%) were identified. DES did not show higher risk of major bleeding than BMS (5.6% vs 6.9%, RR 1.07; 95%CI, 0.89–1.28, p = 0.47; I2 = 0%) or MACE (12% vs 13.6%; RR 0.96; 95%CI 0.81–1.13, p = 0.60; I2 = 44%). Although, DES almost decreased TVR risk (6.4% vs 8.4%, RR 0.78; 95%CI, 0.61–1.01, p = 0.06; I2 = 15%). Stratified analyses by type and duration of antithrombotic therapy showed no differences in major bleeding or MACE between both types of stents. In DES, long-term TAT showed higher major bleeding risk than long-term DAT (7.7% vs 4.7%, RR 1.48, 95%CI 1.08–2.03, p = 0.01; I2 = 12%). For both types of stents, MACE risk was similar between TAT and DAT. Conclusions: In patients with AF undergoing PCI, DES had similar rate of major bleeding and MACE than BMS. DAT seems to be a safer antithrombotic therapy compared with TAT.
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  • Optimizing harvesting for facial lipografting with a new photochemical stimulation concept: One STEP technique™

    Centurión, Patricio; Gamarra, Ronald; Caballero, Gonzalo; Kaufmann, Paul; Delgado, Pia (Springer Science and Business Media Deutschland GmbH, 2020-12-01)
    Background: Facial fat grafting for rejuvenation is one of the most popular facial aesthetic procedures in plastic surgery. It is always challenging and since there are a lot of techniques for adipose tissue (AT) harvesting, there are no standard procedures that guarantee natural and long-lasting results. We developed the selective tissue engineering photo stimulation technique (One STEP™) in which we used a novel infrared 1210-nm wavelength laser diode for fat preserved harvesting and direct fat injection that we named PicoGraft™, with no fat manipulation. Methods: This is a retrospective descriptive study in which we included all senior author’s patients that got facial fat grafting using the One STEP™ technique. We compared the AT aspirated, after laser emission (STEP-PicoGraft) and the standard assisted liposuction samples (SAL) in cultures. We study the mitochondrial activity of the ASC between STEP and SAL in fresh samples and after 24 h. The evaluation of the results included subjective changes regarding wrinkles, grooves, palpebral bags, hyperchromic spots, and fat hypotrophy of our patients. Results: Between July 2013 and May 2018, a total of 245 patients underwent facial fat grafting using this novel technique. We observed adipocytes preserved after STEP harvesting comparing morphologic changes in SAL samples with a high concentration of inflammatory particles in cultures. ASC mitochondrial activity shows an important difference of more than 7 times in STEP samples in fresh analysis that increase 12 times in 24 h. The subjective results show a good improvement in the periorbital area. The changes on the skin and subcutaneous tissue are seen from the second month and continue to improve up to 12 months. Conclusions: Facial fat grafting using the PicoGraft™ obtained by One STEP™ technique gives excellent volumetric and regenerative results in a single treatment without volumetric hypercorrection, and it is a good alternative for facial rejuvenation. The fat graft obtained with this novel technique is homogenous, without lumps, and has high concentration of viable stimulated ADSC and a high number of viable adipocytes. Level of evidence: Level III, therapeutic study.
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  • Phenotypic expansion in KIF1A-related dominant disorders: A description of novel variants and review of published cases

    Montenegro-Garreaud, Ximena; Hansen, Adam W.; Khayat, Michael M.; Chander, Varuna; Grochowski, Christopher M.; Jiang, Yunyun; Li, He; Mitani, Tadahiro; Kessler, Elena; Jayaseelan, Joy; Shen, Hua; Gezdirici, Alper; Pehlivan, Davut; Meng, Qingchang; Rosenfeld, Jill A.; Jhangiani, Shalini N.; Madan-Khetarpal, Suneeta; Scott, Daryl A.; Abarca-Barriga, Hugo; Trubnykova, Milana; Gingras, Marie Claude; Muzny, Donna M.; Posey, Jennifer E.; Liu, Pengfei; Lupski, James R.; Gibbs, Richard A. (John Wiley and Sons Inc, 2020-12-01)
    KIF1A is a molecular motor for membrane-bound cargo important to the development and survival of sensory neurons. KIF1A dysfunction has been associated with several Mendelian disorders with a spectrum of overlapping phenotypes, ranging from spastic paraplegia to intellectual disability. We present a novel pathogenic in-frame deletion in the KIF1A molecular motor domain inherited by two affected siblings from an unaffected mother with apparent germline mosaicism. We identified eight additional cases with heterozygous, pathogenic KIF1A variants ascertained from a local data lake. Our data provide evidence for the expansion of KIF1A-associated phenotypes to include hip subluxation and dystonia as well as phenotypes observed in only a single case: gelastic cataplexy, coxa valga, and double collecting system. We review the literature and suggest that KIF1A dysfunction is better understood as a single neuromuscular disorder with variable involvement of other organ systems than a set of discrete disorders converging at a single locus.
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  • Application of crispr/cas9-based reverse genetics in leishmania braziliensis: Conserved roles for hsp100 and hsp23

    Adaui, Vanessa; Kröber-Boncardo, Constanze; Brinker, Christine; Zirpel, Henner; Sellau, Julie; Arévalo, Jorge; Dujardin, Jean Claude; Clos, Joachim (MDPI AG, 2020-10-01)
    The protozoan parasite Leishmania (Viannia) braziliensis (L. braziliensis) is the main cause of human tegumentary leishmaniasis in the New World, a disease affecting the skin and/or mucosal tissues. Despite its importance, the study of the unique biology of L. braziliensis through reverse genetics analyses has so far lagged behind in comparison with Old World Leishmania spp. In this study, we successfully applied a cloning-free, PCR-based CRISPR–Cas9 technology in L. braziliensis that was previously developed for Old World Leishmania major and New World L. mexicana species. As proof of principle, we demonstrate the targeted replacement of a transgene (eGFP) and two L. braziliensis single-copy genes (HSP23 and HSP100). We obtained homozygous Cas9-free HSP23-and HSP100-null mutants in L. braziliensis that matched the phenotypes reported previously for the respective L. donovani null mutants. The function of HSP23 is indeed conserved throughout the Trypanosomatida as L. major HSP23 null mutants could be complemented phenotypically with transgenes from a range of trypanosomatids. In summary, the feasibility of genetic manipulation of L. braziliensis by CRISPR–Cas9-mediated gene editing sets the stage for testing the role of specific genes in that parasite’s biology, including functional studies of virulence factors in relevant animal models to reveal novel therapeutic targets to combat American tegumentary leishmaniasis.
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  • Unidentified dengue serotypes in DENV positive samples and detection of other pathogens responsible for an acute febrile illness outbreak 2016 in Cajamarca, Peru

    Del Valle-Mendoza, Juana; Vasquez-Achaya, Fernando; Aguilar-luis, Miguel Angel; Martins-Luna, Johanna; Bazán-Mayra, Jorge; Zavaleta-Gavidia, Victor; Silva-Caso, Wilmer; Carrillo-Ng, Hugo; Tarazona-Castro, Yordi; Aquino-Ortega, Ronald; Del Valle, Luis J. (BioMed Central Ltd., 2020-10-06)
    Objective: To describe the prevalence of dengue virus serotypes, as well as other viral and bacterial pathogens that cause acute febrile illness during an outbreak in Cajamarca in 2016. Results: Dengue virus (DENV) was the most frequent etiologic agent detected in 25.8% of samples (32/124), followed by Rickettsia spp. in 8.1% (10/124), Zika virus in 4.8% (6/124), Chikungunya virus 2.4% (3/124) and Bartonella bacilliformis 1.6% (2/124) cases. No positive cases were detected of Oropouche virus and Leptospira spp. DENV serotypes identification was only achieved in 23% of the total positive for DENV, two samples for DENV-2 and four samples for DENV-4. During the 2016 outbreak in Cajamarca-Peru, it was observed that in a large percentage of positive samples for DENV, the infecting serotype could not be determined by conventional detection assays. This represents a problem for the national surveillance system and for public health due to its epidemiological and clinical implications. Other viral and bacterial pathogens responsible for acute febrile syndrome were less frequently identified.
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  • Paediatric snakebite envenoming: the world's most neglected 'Neglected Tropical Disease'?

    Pach, Sophie; Le Geyt, Jacqueline; Gutiérrez, José María; Williams, David; Maduwage, Kalana Prasad; Habib, Abdulrazaq Garba; Gustin, Rafael; Avila-Agüero, María Luisa; Ya, Kyaw Thu; Halbert, Jay (NLM (Medline), 2020-12-01)
    Snakebite disproportionally affects children living in impoverished rural communities. The WHO has recently reinstated snakebites on its list of Neglected Tropical Diseases and launched a comprehensive Strategy for the Prevention and Control of Snakebite Envenoming. In the first of a two paper series, we describe the epidemiology, socioeconomic impact and key prevention strategies. We also explore current challenges and priorities including the production and distribution of safe and effective antivenom.
    Acceso abierto
  • Endemic and epidemic human alphavirus infections in eastern Panama: An analysis of population-based cross-sectional surveys

    Carrera, J. P.; Cucunuba, Zulma M.; Neira, Karen; Lambert, Ben; Pitti, Yaneth; Liscano, Jesus; Garzon, Jorge L.; Beltran, Davis; Collado-Mariscal, Luisa; Saenz, Lisseth; Sosa, Nestor; Rodriguez-Guzman, Luis D.; Gonzalez, Publio; Lezcano, Andres G.; Pereyra-Elias, Renee; Valderrama, Anayansi; Weaver, Scott C.; Vittor, Amy Y.; Armien, Blas; Pascale, Juan Miguel; Donnelly, Christl A. (American Society of Tropical Medicine and Hygiene, 2020-12-01)
    Madariaga virus (MADV) has recently been associated with severe human disease in Panama, where the closely related Venezuelan equine encephalitis virus (VEEV) also circulates. In June 2017, a fatal MADV infection was confirmed in a community of Darien Province. We conducted a cross-sectional outbreak investigation with human and mosquito collections in July 2017, where sera were tested for alphavirus antibodies and viral RNA. In addition, by applying a catalytic, force-of-infection (FOI) statistical model to two serosurveys from Darien Province in 2012 and 2017, we investigated whether endemic or epidemic alphavirus transmission occurred historically. In 2017, MADV and VEEV IgM seroprevalences were 1.6% and 4.4%, respectively; IgG antibody prevalences were MADV: 13.2%, VEEV: 16.8%, Una virus (UNAV): 16.0%, and Mayaro virus: 1.1%. Active viral circulation was not detected. Evidence of MADV and UNAV infection was found near households, raising questions about its vectors and enzootic transmission cycles. Insomnia was associated withMADVand VEEV infections, depression symptoms were associated with MADV, and dizziness with VEEV and UNAV. Force-of-infection analyses suggest endemic alphavirus transmission historically, with recent increased human exposure to MADV and VEEV in Aruza and Mercadeo, respectively. The lack of additional neurological cases suggests that severe MADV and VEEV infections occur only rarely. Our results indicate that over the past five decades, alphavirus infections have occurred at low levels in eastern Panama, but that MADV and VEEV infections have recently increased-potentially during the past decade. Endemic infections and outbreaks of MADV and VEEV appear to differ spatially in some locations of eastern Panama.
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