Sociodemographic and clinical predictors of adherence to antidepressants in depressive disorders: a systematic review with a meta-analysis.

Introduction: Current evidence reveals concerning rates of non-adherence to antidepressant treatment, possibly influenced by various relevant determinants such as sociodemographic factors or those related to the health system and their professionals. The aim of this paper is to review the scientific evidence on sociodemographic and clinical predictors of adherence to pharmacological treatment in patients diagnosed with a depressive disorder. Methods: a systematic review (SR) was conducted. The search for a previous SR was updated and de novo searches were performed in Medline, EMBASE, Web of Science (WoS) and PsycInfo (last 10 years). The risk of bias was assessed using the Cochrane tool for non-randomized studies-of Exposure (ROBINS-E). Meta-analyses were conducted. Results: Thirty-nine studies (n = 2,778,313) were included, 24 of them in the meta-analyses. In the initiation phase, no association of adherence was found with any of the predictors studied. In the implementation and discontinuation phases, middle-aged and older patients had better adherence rates and lower discontinuation rates than younger ones. White patients adhered to treatment better than African-American patients. Discussion: Age and ethnicity are presented as the predictive factors of pharmacological adherence. However, more research is needed in this field to obtain more conclusive results on other possible factors. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023414059], identifier [CRD42023414059].

Percutaneous ethanol injection in thyroid nodular pathology and metastatic cervical adenopathies: A systematic review, meta-analysis and economic evaluation.

BACKGROUND: Percutaneous ethanol injection (PEI) has been shown to be a valuable treatment for thyroid nodular pathology and metastatic cervical adenopathies. OBJECTIVE: To evaluate the effectiveness, safety, and cost-effectiveness of PEI in thyroid nodular pathology and metastatic cervical adenopathies. METHODS: A systematic review (SR) using meta-analysis was conducted on the effectiveness and safety of PEI. A SR on cost-effectiveness was also performed. The SRs were conducted according to the methodology developed by the Cochrane Collaboration with reporting in accordance with the PRISMA statement. A cost-minimization analysis was carried out using a decision tree model. Assuming equal effectiveness between two minimally invasive techniques (PEI and radiofrequency ablation (RFA)), the model compared the costs of the alternatives with a horizon of six months and from the perspective of the Spanish National Health System. RESULTS: The search identified three RCTs (n=157) that evaluated PEI versus RFA in patients diagnosed with benign thyroid nodules: ninety-six patients with predominantly cystic nodules and sixty-one patients with solid nodules. No evidence was found on other techniques or thyroid nodular pathology. No statistically significant differences were observed between PEI and RFA in volume reduction (%), symptom score, cosmetic score, therapeutic success and major complications. No economic evaluations were identified. The cost-minimization analysis estimated the cost per patient of the PEI procedure at €326 compared to €4781 for RFA, which means an incremental difference of -€4455. CONCLUSIONS: There are no differences between PEI and RFA regarding their safety and effectiveness, but the economic evaluation determined that the former option is cheaper.

Occurrence of Alternaria alternata and A. tenuissima causing black rot in cherry fruits (Prunus avium) in Central Chile.

During the harvest of 2020 and 2021, sweet cherry (Prunus avium) fruit showed a firm rot with irregular pale to dark brown lesions on the fruit surface, with green to light brown fungal growth resembling Alternaria-like infection (Simmons, 2007). Diseased cherries (n= 80 fruit) were collected at harvest in mature (over 10-year-old) commercial orchards of cherry tree varieties Lapins, Regina, Santina, Skeena, and Sweetheart planted in four localities of the regions O´Higgins (33°59´ S, 70°42´W; San Francisco de Mostazal and Graneros) and Maule (35°00'S, 71°23´W; Curicó and Sagrada Familia), Central Chile. The incidence of black rot was 1.9 and 3.2% in O´Higgins and Maule region, respectively, and it was increased to up to 5% during cold storage. The fruit collected previously, were transported to the lab, and surface disinfected in 75% ethanol for 15 s, and rinsed in sterile water. Internal pieces from the junction of diseased and healthy tissues of fruits were placed on potato dextrose agar (PDA, 2%) for 7 days at 20°C. Forty-two isolates of Alternaria-like (Simmons, 2007) were recovered consistently from pure cultures taking hyphal tips from 7 days old cultures. On PDA, 28 isolates (group A) were characterized by cottony, white-gray to green colonies and conidial chains (4 to 10 conidia) with secondary chains (1 to 5 conidia) branching on the conidiophore. Conidia were ovate to obclavate (mean 22.8 ± 5.1 x 8.8 ± 1.5 µm; n=40) with 3 to 7 transepta and 1 longisepta. The remaining 14 isolates (group B) were characterized by cottony, olive-green to olive-brown colonies following a ring pattern of growth and white margins, with conidial chains (4 to 14 conidia) and uncommon secondary chains (1 to 4 conidia). Conidia were obpyriform to ovate, light brown to brown with a cylindrical short beak at the tip (mean 24.7 ± 5.9 × 11.2 ± 1.3 µm; n=40) with 2 to 4 transepta, and 0 to 2 longisepta. Two representative isolates of group A (Sant-02-2020 and Bing-03-2020) and group B (Sant-26-2021 and Skeen-43-2021) were amplified for the Alternaria major allergen (Alt a1), plasma membrane ATPase (ATP), and calmodulin (Cal) loci following the protocols described by Hong et al. (2005) and Lawrence et al. (2013). A MegaBlast search of sequences of group A (GenBank nos. OR267293- OR267294, OR258001- OR258002, and OR267297- OR267298, for Alt a1, ATP, and Cal, respectively) showed 100% similarity to strains UCD10529 and UCD10539 of A. alternata, and group B (GenBank nos. OR267295- OR267296, OR258003- OR258004, and OR258005- OR258006, for Alt a1, ATP, and Cal, respectively) showed 100% similarity to strains EGS 34-015 and A30 of A. tenuissima. Combined phylogenetic analysis using MEGA X clustered isolates Sant-02-2020 and Bing-03-2020, and Sant-26-2021 and Skeen-43-2021 with ex-type of A. alternata and A. tenuissima, respectively. Pathogenicity tests were conducted using isolates of A. alternata (Sant-02-2020; Bing-03-2020) and A. tenuissima (Sant-26-2021; Skeen-43-2021). Detached ripe cherry fruit var. Sweetheart (n=40 fruits/isolate) and Regina (n=40 fruits/isolate) were surfaces disinfested (75% ethanol, 30 s), wounded in the middle with a sterile needle (2 mm in depth), and inoculated with 20 µL of conidial suspension (106 conidia/mL). An equal number of healthy cherries (n=40 fruits) treated with sterile water were used as controls. The experiment was repeated once. All inoculated fruit incubated for 7 days at 22°C, developed between 13 ± 2.7 to 23 ± 2.5 mm and 14.1 ± 1.1 to 19 ± 3.6 mm in lesion diameter for A. alternata and A. tenuissima isolates, respectively. Koch´s postulates were fulfilled by 100% reisolation of the causal pathogen from inoculated fruit, and molecular identification of A. alternata and A. tenuissima isolates. Previously, A. alternata has been described as causing rots on cherries in Chile (Acuña 2010), and China (Zhao and Liu, 2012; Ahmad et al., 2020). To our knowledge, this is the first occurrence of cherry black rot caused by A. alternata and A. tenuissima in Central Chile. Epidemiological studies are necessary to develop integrated management of cherry black rot in Central Chile.

[Scalp cooling for the prevention of chemotherapy-induced alopecia: systematic review and meta-analysis.] / Enfriamiento del cuero cabelludo para la prevención de la alopecia secundaria a quimioterapia: revisión sistemática y metanálisis.

OBJECTIVE: Alopecia is one of the most common adverse effects of chemotherapy, having a significant impact on the quality of life of patients who suffer from it. Among the interventions available for its prevention, scalp cooling (SC) is the most widely used. The aim of this study was to assess the efficacy and safety of the use of SC systems during chemotherapy sessions for the prevention or the reduction of the extent of chemotherapy-induced alopecia. METHODS: A systematic review of the literature published up to November 2021 was carried out. Randomized clinical trials were selected. The main outcome measure was alopecia (hair loss>50%) during and after chemotherapy treatment. When possible, a quantitative synthesis of the results was performed through meta-analysis using the Stata v.15.0 software. The risk ratio (RR) of the variable alopecia, was estimated using a random effects model following the Mantel-Haenszel method. Statistical heterogeneity of the results was evaluated graphically and through the test of heterogeneity χ2 and the Higgins I2 statistic. Sensitivity analyses and subgroup analyses were performed. RESULTS: 13 studies were included, with a total of 832 participants (97.7% women). In most studies, the main chemotherapy treatment applied was anthracyclines or the combination of anthracyclines and taxanes. The results obtained indicate that SC prevents alopecia (loss>50%) by 43% compared to the control group (RR=0.57; 95% CI=0.46 to 0.69; k=9; n=494; I2=63.8%). No statistically significant difference was found between the efficacy of automated and non-automated cooling systems (P=0.967). No serious short- or medium-term adverse events related to SC were recorded. CONCLUSIONS: The results suggest that scalp cooling contributes to the prevention of chemotherapy-induced alopecia.

OBJETIVO: La alopecia es uno de los efectos adversos más comunes de la quimioterapia, con un impacto importante sobre la calidad de vida de los/las pacientes que la padecen. Entre las intervenciones disponibles para su prevención, el enfriamiento del cuero cabelludo (ECC) es la que cuenta con un uso más extendido. El objetivo de este estudio fue evaluar la eficacia y la seguridad del uso de sistemas de ECC durante las sesiones de quimioterapia para la prevención o reducción de la extensión de la alopecia secundaria a la quimioterapia. METODOS: Se llevó a cabo una revisión sistemática de la literatura publicada hasta noviembre de 2021. Se seleccionaron ensayos clínicos aleatorizados. La medida de resultado principal fue la alopecia (pérdida de cabello superior al 50%) durante y posteriormente al tratamiento de quimioterapia. Cuando fue posible, se realizó síntesis cuantitativa de los resultados mediante metanálisis con el programa Stata v.15.0. Se estimó el riesgo relativo (RR) de la variable alopecia, utilizando un modelo de efectos aleatorios siguiendo el método de Mantel-Haenszel. La heterogeneidad estadística de los resultados se evaluó gráficamente y mediante el test de la χ2 y el estadístico I2 de Higgins. Se realizaron análisis de sensibilidad y análisis de subgrupos. RESULTADOS: Se incluyeron 13 estudios con un total de 832 participantes (97,7% de mujeres). En la mayoría de los estudios, los agentes quimioterapéuticos principales aplicados fueron las antraciclinas o la combinación de antraciclinas y taxanos. Los resultados obtenidos indican que el ECC reduce la aparición de la alopecia un 43% frente al grupo control (RR=0,57; IC95%=0,46 a 0,69; k=9; n=494; I2=63,8%). No se encontró una diferencia estadísticamente significativa entre la eficacia de sistemas de enfriamiento automatizados y no automatizados (P=0,967). No se registraron eventos adversos graves a corto o medio plazo relacionados con el ECC. CONCLUSIONES: Los resultados sugieren que el ECC contribuye a prevenir la alopecia secundaria a la quimioterapia.

Enfriamiento del cuero cabelludo para la prevención de la alopecia secundaria a quimioterapia: revisión sistemática y metanálisis / Scalp cooling for the prevention of chemotherapy-induced alopecia: systematic review and meta-analysis

Fundamentos: La alopecia es uno de los efectos adversos más comunes de la quimioterapia, con un impacto importante sobrela calidad de vida de los/las pacientes que la padecen. Entre las intervenciones disponibles para su prevención, el enfriamiento delcuero cabelludo (ECC) es la que cuenta con un uso más extendido. El objetivo de este estudio fue evaluar la eficacia y la seguridaddel uso de sistemas de ECC durante las sesiones de quimioterapia para la prevención o reducción de la extensión de la alopeciasecundaria a la quimioterapia. Métodos: Se llevó a cabo una revisión sistemática de la literatura publicada hasta noviembre de 2021. Se seleccionaron ensayosclínicos aleatorizados. La medida de resultado principal fue la alopecia (pérdida de cabello superior al 50%) durante y posteriormenteal tratamiento de quimioterapia. Cuando fue posible, se realizó síntesis cuantitativa de los resultados mediante metanálisis con elprograma Stata v.15.0. Se estimó el riesgo relativo (RR) de la variable alopecia, utilizando un modelo de efectos aleatorios siguiendoel método de Mantel-Haenszel. La heterogeneidad estadística de los resultados se evaluó gráficamente y mediante el test de la χ2 yel estadístico I2 de Higgins. Se realizaron análisis de sensibilidad y análisis de subgrupos. Resultados: Se incluyeron 13 estudios con un total de 832 participantes (97,7% de mujeres). En la mayoría de los estudios, losagentes quimioterapéuticos principales aplicados fueron las antraciclinas o la combinación de antraciclinas y taxanos. Los resultadosobtenidos indican que el ECC reduce la aparición de la alopecia un 43% frente al grupo control (RR=0,57; IC95%=0,46 a 0,69; k=9;n=494; I2=63,8%). No se encontró una diferencia estadísticamente significativa entre la eficacia de sistemas de enfriamiento auto-matizados y no automatizados (P=0,967). No se registraron eventos adversos graves a corto o medio plazo relacionados con el ECC...(AU)

Background: Alopecia is one of the most common adverse effects of chemotherapy, having a significant impact on the qualityof life of patients who suffer from it. Among the interventions available for its prevention, scalp cooling (SC) is the most widely used. The aim of this study was to assess the efficacy and safety of the use of SC systems during chemotherapy sessions for the preventionor the reduction of the extent of chemotherapy-induced alopecia.Methods: A systematic review of the literature published up to November 2021 was carried out. Randomized clinical trials were selected. The main outcome measure was alopecia (hair loss>50%) during and after chemotherapy treatment. When possible, a quantitative synthesisof the results was performed through meta-analysis using the Stata v.15.0 software. The risk ratio (RR) of the variable alopecia, was estimatedusing a random effects model following the Mantel-Haenszel method. Statistical heterogeneity of the results was evaluated graphically andthrough the test of heterogeneity χ2 and the Higgins I2 statistic. Sensitivity analyses and subgroup analyses were performed. Results: 13 studies were included, with a total of 832 participants (97.7% women). In most studies, the main chemotherapy treat-ment applied was anthracyclines or the combination of anthracyclines and taxanes. The results obtained indicate that SC preventsalopecia (loss>50%) by 43% compared to the control group (RR=0.57; 95% CI=0.46 to 0.69; k=9; n=494; I2=63.8%). No statisticallysignificant difference was found between the efficacy of automated and non-automated cooling systems (P=0.967). No serious short-or medium-term adverse events related to SC were recorded. Conclusions: The results suggest that scalp cooling contributes to the prevention of chemotherapy-induced alopecia.(AU)

Ethical, Legal, Organisational and Social Issues of Teleneurology: A Scoping Review.

BACKGROUND: Neurological disorders are the leading cause of disability and the second leading cause of death worldwide. Teleneurology (TN) allows neurology to be applied when the doctor and patient are not present in the same place, and sometimes not at the same time. In February 2021, the Spanish Ministry of Health requested a health technology assessment report on the implementation of TN as a complement to face-to-face neurological care. METHODS: A scoping review was conducted to answer the question on the ethical, legal, social, organisational, patient (ELSI) and environmental impact of TN. The assessment of these aspects was carried out by adapting the EUnetHTA Core Model 3.0 framework, the criteria established by the Spanish Network of Health Technology Assessment Agencies and the analysis criteria of the European Validate (VALues In Doing Assessments of healthcare TEchnologies) project. Key stakeholders were invited to discuss their concerns about TN in an online meeting. Subsequently, the following electronic databases were consulted from 2016 to 10 June 2021: MEDLINE and EMBASE. RESULTS: 79 studies met the inclusion criteria. This scoping review includes 37 studies related to acceptability and equity, 15 studies developed during COVID and 1 study on environmental aspects. Overall, the reported results reaffirm the necessary complementarity of TN with the usual face-to-face care. CONCLUSIONS: This need for complementarity relates to factors such as acceptability, feasibility, risk of dehumanisation and aspects related to privacy and the confidentiality of sensitive data.

Telemedicine for neurological diseases: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: The aim was to systematically review the effectiveness and safety of telemedicine combined with usual care (in-person visits) compared to usual care for the therapeutic management and follow-up assessment of neurological diseases. METHODS: The electronic databases MEDLINE, Embase, Web of Science and Cochrane Central Register of Controlled Trials were searched (June 2021). Randomized controlled trials (RCTs) on patients of any age with neurological diseases were considered. Two reviewers screened and abstracted data in duplicate and independently and assessed risk of bias using the Cochrane risk-of-bias tool for randomized trials (RoB 2). When possible, pooled effect estimates were calculated. RESULTS: Of a total of 3018 records initially retrieved, 25 RCTs (n = 2335) were included: 11 (n = 804) on stroke, four (n = 520) on Parkinson's disease, three (n = 110) on multiple sclerosis, two (n = 320) on epilepsy, one (n = 63) on dementia, one (n = 23) on spina bifida, one (n = 40) on migraine, one (n = 22) on cerebral palsy and one (n = 433) on brain damage. Types of telemedicine assessed were online visits (11 studies), tele-rehabilitation (seven studies), telephone calls (three), smartphone apps (two) and online computer software (two). The evidence was quite limited except for stroke. Compared to usual care alone, telemedicine plus usual care was found to improve depressive symptoms, functional status, motor function, executive function, generic quality of life, healthcare utilization and healthy lifestyle in patients in post-stroke follow-up. CONCLUSIONS: Well-designed and executed RCTs are needed to confirm our findings on stroke and to have more scientific evidence available for the other neurological diseases.

Dothiorella sarmentorum Causing Branch Dieback of English Walnut in Maule Region, Chile.

English walnut (Juglans regia), cv. Chandler is the most cultivated tree nut in Chile, with 43,734 ha. In Maule Region, central Chile, English walnut plantings have expanded over an additional 7,000 ha in the last five years. During a routine orchard survey in 2019, branch and twig dieback symptoms were observed in two commercial orchards located in San Rafael (10 years old) and Longaví (12 years old) in the Maule Region, with an incidence of 45% to 65% of affected trees, respectively. Symptomatic branch samples (n = 15) were collected from the two commercial orchards and transported to the laboratory in a cooler and then surface sterilized in 96% ethanol for 3 s and briefly flamed. Cross-section of symptomatic branches revealed brown to dark-brown wedge-shaped wood cankers. Small (5 mm) pieces of wood from the edge of cankered tissues were placed on Potato Dextrose Agar (PDA, 2%) amended with 0.005% tetracycline, 0.01% streptomycin, and 0.1% Igepal CO-630 (PDAm) (Díaz and Latorre 2014) and incubated at 25°C for five days in the dark. Pure cultures were obtained by transferring a hyphal tip from growing colonies to fresh PDA media. Each fungal isolate was recovered from a single diseased branch (47%). Seven isolates (Dsar-1 to Dsar-7) developed dark to olive-brown fast-growing colonies with scarce aerial mycelium after seven days at 25°C on PDA. These isolates showed a dark-olive color on the reverse side of Petri dishes and developed abundant, aggregated, and dark-brown pycnidia after 15 days at 25°C. Conidia were hyaline and aseptate, dark brown, 1-septate, with a brown wall, ovoid with a broadly rounded apex and truncated base, (17.5-) 19.5 ±1.2 (-22.0) x (7.6-) 8.9 ± 0.6 (-10.1) µm (n = 30). These isolates were tentatively identified morphologically as Dothiorella sp. (Phillips et al. 2005). Molecular identification was performed using ITS1/ITS4 and EF1-728F/EF1-986R primers (White et al. 1990; Dissanayake et al. 2015) of the internal transcribed spacer (ITS1-5.8S-ITS2) region and part of the translation elongation factor (EF1-) genes, respectively. A MegaBlast search in GenBank showed a 100% similarity to isolate CBS 115038, the ex-type of Dothiorella sarmentorum. The sequences were added to GenBank (OM161950 to OM161956 for ITS; OM177188 to OM177194 for EF1-). Pathogenicity of two isolates (Dsar-2 and Dsar-7) was tested in the orchard on freshly made pruning wounds on attached branches of 2-year-old-pruned English walnut trees cv. Chandler. A second pathogenicity test was done on freshly made pruning wounds in 1-year-old rooted cuttings (n=15) (40 cm of long) of English walnut cv. Chandler. Each pruning wound was inoculated with 40 µL conidial suspension (105 conidia/mL). Sterile distilled water was used as a control treatment. Both pathogenicity tests were repeated once. After seven months for attached branches and four months for rooted plants, necrotic streaks with a mean length of 81.3 and 44.5 mm were observed below the inoculated pruning wounds, respectively. No necrotic streaks were observed in any of the control wounds. Dothiorella sarmentorum was 100% reisolated from symptomatic tissues of inoculated branches and molecularly identified (EF1-), thus fulfilling Koch's postulates. Recently, D. sarmentorum has been reported causing English walnut dieback in Spain (López-Moral et al. 2020). To our knowledge, this is the first report of D. sarmentorum causing branch dieback of English walnut in Chile. Further studies are needed to know the impact and extent of canker and branch dieback of walnut in commercial orchards in the Maule Region, central Chile.

Evaluation of the transcriptional immune biomarkers in peripheral blood from Warao indigenous associate with the infection by Mycobacterium tuberculosis.

INTRODUCTION: Biomarkers are critical tools for finding new approaches for controlling the spread of tuberculosis (TB), including for predicting the development of TB therapeutics, vaccines, and diagnostic tools. METHODS: Expression of immune biomarkers was analyzed in peripheral blood cells stimulated and non-stimulated with M. tuberculosis antigens ESAT-6, CFP10 and TB7.7. in Warao indigenous individuals. These biomarkers may be able to differentiate TB states, such as active tuberculosis (ATB) cases and latent tuberculosis infection (LTBI) from non-infected controls (NIC). A real-time reverse transcription polymerase chain reaction (RT-qPCR) assay was performed on 100 blood samples under non-stimulation or direct ex vivo conditions (NS=50) and stimulation conditions (S=50). RESULTS: The findings are shown as the median and interquartile range (IQR) of relative gene expression levels of IFN-γ, CD14, MMP9, CCR5, CCL11, CXCL9/MIG, and uPAR/PLAUR immune biomarkers. MMP9 levels were significantly higher in the LTBI-NS and LTBI-S groups compared with the NIC-NS and NIC-S groups. However, CCR5 levels were significantly lower in the LTBI-S group compared with both NIC-NS and NIC-S groups. CCL11 levels were significantly lower in the LTBI-S group compared with the NIC-NS group. CONCLUSIONS: Preliminary findings showed that MMP9 immune biomarkers separated LTBI indigenous individuals from NIC indigenous individuals, while CCR5, CCL11, CD14, and IFN-γ did not differentiate TB states from NIC. MMP9 may be useful as a potential biomarker for LTBI and new infected case detection among Warao indigenous individuals at high risk of developing the disease. It may also be used to halt the epidemic, which will require further validation in larger studies.

Evaluation of the transcriptional immune biomarkers in peripheral blood from warao indigenous associate with the infection by mycobacterium tuberculosis

Abstract INTRODUCTION: Biomarkers are critical tools for finding new approaches for controlling the spread of tuberculosis (TB), including for predicting the development of TB therapeutics, vaccines, and diagnostic tools. METHODS: Expression of immune biomarkers was analyzed in peripheral blood cells stimulated and non-stimulated with M. tuberculosis antigens ESAT-6, CFP10 and TB7.7. in Warao indigenous individuals. These biomarkers may be able to differentiate TB states, such as active tuberculosis (ATB) cases and latent tuberculosis infection (LTBI) from non-infected controls (NIC). A real-time reverse transcription polymerase chain reaction (RT-qPCR) assay was performed on 100 blood samples under non-stimulation or direct ex vivo conditions (NS=50) and stimulation conditions (S=50). RESULTS: The findings are shown as the median and interquartile range (IQR) of relative gene expression levels of IFN-γ, CD14, MMP9, CCR5, CCL11, CXCL9/MIG, and uPAR/PLAUR immune biomarkers. MMP9 levels were significantly higher in the LTBI-NS and LTBI-S groups compared with the NIC-NS and NIC-S groups. However, CCR5 levels were significantly lower in the LTBI-S group compared with both NIC-NS and NIC-S groups. CCL11 levels were significantly lower in the LTBI-S group compared with the NIC-NS group. CONCLUSIONS: Preliminary findings showed that MMP9 immune biomarkers separated LTBI indigenous individuals from NIC indigenous individuals, while CCR5, CCL11, CD14, and IFN-γ did not differentiate TB states from NIC. MMP9 may be useful as a potential biomarker for LTBI and new infected case detection among Warao indigenous individuals at high risk of developing the disease. It may also be used to halt the epidemic, which will require further validation in larger studies.

Type I Interferon Gene Response Is Increased in Early and Established Rheumatoid Arthritis and Correlates with Autoantibody Production.

BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory debilitating disease that affects the joints in the early and productive phases of an individual's life. Several cytokines have been linked to the disease pathogenesis and are known to contribute to the inflammatory state characteristic of RA. The participation of type I interferon (IFN) in the pathogenesis of the disease has been already described as well as the identity of the genes that are regulated by this molecule, which are collectively known as the type I IFN signature. These genes have several functions associated with apoptosis, transcriptional regulation, protein degradation, Th2 cell induction, B cell proliferation, etc. This article evaluated the expression of several genes of the IFN signature in different stages of disease and their correlation with the levels of anticitrullinated protein antibodies (ACPA) anticarbamylated protein (Anti-CarP) antibodies. METHODS: Samples from individuals with early and established RA, high-risk individuals (ACPA+ and ACPA-), and healthy controls were recruited at "Unidad de Artritis y Rheumatismo" (Rheumatism and Arthritis Unit) in Guadalajara Jalisco Mexico. Determinations of ACPA were made with Eurodiagnostica ACPA plus kit. Anti-CarP determinations were made according to previously described protocols. RNA was isolated, and purity and integrity were determined according to RNA integrity number >6. Gene expression analysis was made by RT-qPCR using specific primers for mRNAs of the type I IFN signature. Relative gene expression was calculated according to Livak and Schmitgen. RESULTS: Significant differences in gene expression were identified when comparing the different groups for MXA and MXB (P < 0.05), also when comparing established RA and ACPA- in both IFIT 1 and G15. An increased expression of ISG15 was identified (P < 0.05), and a clear tendency toward increase was identified for HERC5. EPSTRI1, IFI6, and IFI35 were found to be elevated in the chronic/established RA and early RA (P < 0.05). Significant correlations were identified for the IFN signature genes with the levels of ACPA and anti-CarP (P < 0.05). CONCLUSION: Our data confirm previous observations in the role of IFN signature and the pathogenesis of RA. Also, we provide evidence of an association between several genes of the IFN signature (that regulate Th2 cells and B cell proliferation) with the levels of anti-CarP antibodies and ACPA.

Associated Risk Factors for Latent Tuberculosis Infection in Subjects with Diabetes.

BACKGROUND AND AIMS: Type 2 diabetes mellitus (DM2) confers a higher risk for active tuberculosis (TB). However, information on associated risk factors for latent tuberculosis infection (LTBI) inpatients with DM2 is limited. We conducted a cross-sectional study to elucidate the prevalence of LTBI and its associated factors on Mexican adults with DM2 receiving medical care at the Mexican Social Security Institute (IMSS). METHODS: Six hundred patients with DM2 without a prior history of TB from outpatient diabetes clinics were enrolled in the study. The tuberculin-skin-test (TST) was performed. The presence of LTBI was defined by a TST value of ≥ 5 mm. A standardized interview and physical examination were conducted to obtain clinical, demographic, and LTBI risk factor information; all subjects were laboratory tested to determine the presence of exclusion criteria. Microscopic examination of sputum samples and chest x-rays was performed to identify potential active TB. Subjects with any finding suggesting active TB or malignancy were excluded. A logistic regression model was used to identify variables associated with LTBI. RESULTS: LTBI prevalence among patients with DM2 was 51.3%. Risk factors for LTBI were living with a relative with TB, having been in prison, having hemoglobin values >14 g/dL, and glycosylated hemoglobin (HbA1c) values of > 7%. Blood pressure, economic income, or anthropometric measurements were not associated risk factors. CONCLUSIONS: Over one half of patients with DM harbor LTBI. Exposure to certain environmental conditions and poorly controlled DM2 (HbA1c > 7.0%) were risk factors for having LTBI in persons with DM2.

Caracterización de la motivación por la asignatura de matemática en los estudiantes de la carrera de Optometría y Óptica / Characterization of the motivation for mathematics in students majoring in Optometry and Optics

La necesidad de motivar a los estudiantes por el aprendizaje en las diferentes asignaturas constituye un eslabón fundamental en el proceso docente educativo. Se realizó un estudio descriptivo para caracterizar la motivación por la asignatura de Matemática en los estudiantes de la carrera de Optometría y Óptica. Para ello se realizó un diagnóstico a 20 estudiantes del tercer año de la referida carrera, en la Filial de Ciencias Médicas Mario Muñoz Monroy, perteneciente a la Universidad de Ciencias Médicas de Las Tunas; el período de estudio abarcó desde septiembre de 2012 hasta enero de 2013. Para la caracterización de los estudiantes se emplearon los siguientes métodos y técnicas: revisión documental de informes de promoción, diagnóstico pedagógico y encuesta a estudiantes y profesores. Los resultados de la caracterización evidenciaron la falta de motivación de los estudiantes por la asignatura de Matemática e insuficiente rendimiento académico en el aprendizaje de la misma; permitió caracterizar además el nivel de conocimientos que poseen los estudiantes (AU)

The need to motivate the students to learn through the different subjects of the specialties of Health Technology is an essential component of the educational process. A descriptive study was carried out in order to describe the motivation for Mathematics in students majoring in Optometry and Optics. A diagnosis to 20 third-year students of the above specialty was made at Mario Muñoz Monroy Affiliated School of Medical Sciences of the University of Medical Sciences of Las Tunas, from September, 2012 to January, 2013. For the characterization of the students the following methods and techniques were used: document checking of grade reports, pedagogical diagnosis, and surveys to students and teachers. The characterization results revealed a lack of motivation among the students for Mathematics and a poor academic performance in the learning of the subject. The study provided information on the students knowledge level, what helped to determine the ones who made progress more efficiently and the ones who needed help (AU)

Estrategia didáctica para el desarrollo de habilidades en la resolución de problemas matemáticos, carrera de Optometría y Óptica / Didactic Strategy for the Development of Abilities in Solving Mathematic Problems, Optometry and Optic Career

El presente trabajo es una propuesta de estrategia didáctica para favorecer el proceso de enseñanza- aprendizaje de la Matemática, específicamente en el campo de la resolución de problemas matemáticos relacionados con la profesión de Optometría y Óptica. Se realizó un estudio diagnóstico a 20 estudiantes del primer año de la referida carrera en la Filial de Ciencias Médicas Mario Muñoz Monroy, Universidad de Ciencias Médicas de Las Tunas, en el período de septiembre de 2010 a enero de 2011. El estado real de los alumnos fue diagnosticado a través de diferentes métodos, técnicas e instrumentos, propios de la investigación pedagógica. La muestra objeto de estudio se caracterizó en cuanto a edad, sexo, vías de ingreso e insuficiencias en el aprendizaje de la asignatura Matemática. Además, se revisaron los análisis realizados en los colectivos de asignaturas, año y carrera, los informes de promoción sobre la calidad del rendimiento académico en los últimos cinco años, las evaluaciones frecuentes, parciales y finales. También se tuvo en consideración la experiencia profesional de los autores. Se elaboró una estrategia conformada por acciones, teniendo en cuenta habilidades y objetivos que se quieren alcanzar, considerando los niveles de desempeño cognitivos. La estrategia es didáctica, desarrolladora, flexible y dinámica e incluye un plan de acciones factibles de aplicar para otras asignaturas y carreras (AU)

This paper is a teaching strategy proposal to promote the teaching and learning of mathematics, specifically in the field of mathematical problem solving related to the profession of Optometry and Optics. A diagnostic study was carried out to 20 students from first year of that career in the Medical Sciences Branch Mario Muñoz Monroy, University of Medical Sciences of Las Tunas, from September, 2010 to January, 2011. The actual status of the students was diagnosed by different methods, techniques and instruments of educational research. The study sample was characterized in terms of age, sex, income and inadequacies pathways in learning in Mathematics. In addition, the analysis performed in the groups of subjects, year and career, promotion reports on the quality of academic performance in the past five years, as well as frequent, midterm, and final assessments, were checked. It also took into account the professional experience of the authors. A strategy composed of actions, taking into account skills and objectives to be achieved, considering the levels of cognitive performance, was made. The strategy is didactic, developing, flexible and dynamic and includes a feasible action plan to be applied to other subjects and careers (AU)

Common mutations in Cuban cystic fibrosis patients.

So far, more than 1500 mutations have been reported in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Mutational spectrum varies in accordance with geographic and/or ethnic origin. In this study, we have analyzed seven common CF mutations (p.F508del, p.G542X, p.R1162X, p.N1303K, p.R334W, p.R553X and c.3120+1G>A) taking into account the ethnic origin of the Cuban population which is mainly influenced by Spanish and sub-Sahara African contribution. All but p.N1303K have been detected in our patients, the p.F508del being the most prevalent (37.9%). Overall, six mutations showed frequencies above 1% accounting for 55.5% of the Cuban CF alleles.

Inheritance of immune polarization patterns is linked to resistance versus susceptibility to Cryptococcus neoformans in a mouse model.

Genetic background variation between inbred strains accounts for different levels of susceptibility to Cryptococcus neoformans in the mouse infection model. To elucidate the inheritance of immunophenotypic traits and their associations with clearance outcomes during cryptococcal infection, we compared C57BL/6, BALB/c, and their first-generation hybrid, CB6F1 (F1), mice. Mice from each group were infected with C. neoformans (10(4) CFU) and analyzed at weekly intervals over a 6-week period. BALB/c mice progressively cleared the cryptococcal infection in the lungs and showed a Th1-skewed immune response: a Th1-shifted cytokine profile, modest lung pathology, and no significant elevation in the systemic immunoglobulin E (IgE) level. In contrast, C57BL/6 mice developed a chronic infection with a Th2-skewed immune response: a Th2-shifted cytokine profile, pulmonary eosinophilia, severe lung pathology, elevated serum IgE, fungemia, and cryptococcal dissemination in the central nervous system. F1 mice demonstrated intermediate resistance to C. neoformans, with a stronger resemblance to the immunophenotype of the resistant (BALB/c) mice. F1 mice also demonstrated enhanced pulmonary recruitment of lymphocytes, especially CD8(+) T cells, in comparison to both parental strains, suggesting positive heterosis. We conclude that the inheritance of traits responsible for early cytokine induction in the infected lungs and dendritic-cell maturation/activation status in draining nodes is responsible for the intermediate immune response polarization and clearance outcome observed initially in the lungs of F1 mice. The enhanced pulmonary lymphocyte recruitment could be responsible for a gradual shutdown of the undesirable Th2 arm of the immune response and subsequently improved anticryptococcal resistance in F1 mice.

Role of IFN-gamma in regulating T2 immunity and the development of alternatively activated macrophages during allergic bronchopulmonary mycosis.

Pulmonary Cryptococcus neoformans infection of C57BL/6 mice is an established model of a chronic pulmonary fungal infection accompanied by an "allergic" response (T2) to the infection, i.e., a model of an allergic bronchopulmonary mycosis. Our objective was to determine whether IFN-gamma plays a role in regulating the pulmonary T2 immune response in C. neoformans-infected C57BL/6 mice. Long-term pulmonary fungistasis was lost in IFN-gamma knockout (KO) mice, resulting in an increased pulmonary burden of fungi at wk 3. IFN-gamma was required for the early influx of leukocytes into the lungs but was not required later in the infection. By wk 3, eosinophil and macrophage numbers were elevated in the absence of IFN-gamma. The inducible NO synthase to arginase ratio was lower in the lungs of IFN-gamma KO mice and the macrophages had increased numbers of intracellular cryptococci and YM1 crystals, indicative of alternatively activated macrophages in these mice. There was evidence of pulmonary fibrosis in both wild-type and IFN-gamma KO mice by 5 wk postinfection. IFN-gamma production was not required for the development of T2 cytokine (IL-4, IL-5, IL-13) producing cells in the lungs and lung-associated lymph nodes or induction of an IgE response. At a number of time points, T2 cytokine production was enhanced in IFN-gamma KO mice. Thus, in the absence of IFN-gamma, C57BL/6 mice develop an augmented allergic response to C. neoformans, including enhanced generation of alternatively activated macrophages, which is accompanied by a switch from a chronic to a progressive pulmonary cryptococcal infection.

Distinct roles for IL-4 and IL-10 in regulating T2 immunity during allergic bronchopulmonary mycosis.

Pulmonary Cryptococcus neoformans infection of C57BL/6 mice is an established model of an allergic bronchopulmonary mycosis that has also been used to test a number of immunomodulatory agents. Our objective was to determine the role of IL-4 and IL-10 in the development/manifestation of the T2 response to C. neoformans in the lungs and lung-associated lymph nodes. In contrast to wild-type (WT) mice, which develop a chronic infection, pulmonary clearance was significantly greater in IL-4 knockout (KO) and IL-10 KO mice but was not due to an up-regulation of a non-T cell effector mechanism. Pulmonary eosinophilia was absent in both IL-4 KO and IL-10 KO mice compared with WT mice. The production of IL-4, IL-5, and IL-13 by lung leukocytes from IL-4 KO and IL-10 KO mice was lower but IFN-gamma levels remained the same. TNF-alpha and IL-12 production by lung leukocytes was up-regulated in IL-10 KO but not IL-4 KO mice. Overall, IL-4 KO mice did not develop the systemic (lung-associated lymph nodes and serum) or local (lungs) T2 responses characteristic of the allergic bronchopulmonary C. neoformans infection. In contrast, the systemic T2 elements of the response remained unaltered in IL-10 KO mice whereas the T2 response in the lungs failed to develop indicating that the action of IL-10 in T cell regulation was distinct from that of IL-4. Thus, although IL-10 has been reported to down-regulate pulmonary T2 responses to isolated fungal Ags, IL-10 can augment pulmonary T2 responses if they occur in the context of fungal infection.

Role and development of TH1/TH2 immune responses in the lungs.

The development of T helper 1 (Th1) and Th2 responses is dependent on the cells and early signals of the innate immune system. Following inhalation of pulmonary pathogens, lung antigen-presenting cells (APCs) ingest the microbe, begin to process antigen, and migrate to peripheral lymphoid tissues (i.e., LALNs). It is in the lymph node that the APC-T cell interaction takes place; therefore, the microenvironment of the lymph node significantly influences the developing T cell response (Th1 vs Th2). Several factors can determine the nature of the T cell response, including cytokines, chemokines, microbial virulence factors, and dendritic cell phenotype. A shift in the Th1/Th2 balance in the lungs can result in chronic infection, allergic disease, and immunopathology. This review discusses the mechanisms of developing Th1/Th2 pulmonary responses, the counterregulation of Th1/Th2 immunity, and the consequences of immune deviation in the lungs.

Pulmonary defenses against fungi.

Pulmonary immunity to fungal pathogens requires both innate and adaptive immune responses. Alveolar macrophages, dendritic cells, and neutrophils are the phagocytic cells of the lung innate system. These cells produce early inflammatory mediators (i.e., reactive oxygen species, cytokines, and chemokines) in response to fungal infection. The production of early cytokines by innate cells, namely tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-12, plays a central role in the development of protective cell-mediated immunity against fungi. T helper 1 (Th1) cell-mediated immunity is essential for limiting a pulmonary fungal infection. Virulence factors produced by the fungi can also modulate the host immune response. Fungal virulence factors include the production of prostaglandins and a polysaccharide capsule. The type of adaptive immune response (T1 vs T2) generated determines whether the fungi are cleared from the lungs or a chronic fungal infection prevails.