Publications by authors named "J Jaime Miranda"

2,015 Publications

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Development and optimization of a TaqMan assay for Nosema bombycis, causative agent of pébrine disease in Bombyx mori silkworm, based on the β-tubulin gene.

J Microbiol Methods 2021 May 12:106238. Epub 2021 May 12.

Genomic Division, Seri Biotech Research Laboratory, Carmelaram Post, Kodathi, Bengaluru 560035, India.

"Pébrine" is a devastating disease of Bombyx mori silkworms that is highly contagious and can completely destroy an entire crop of silkworms and is thus a serious threat for the viability and profitability of sericulture. The disease is most commonly attributed to microsporidians of the genus Nosema, which are obligate intracellular parasites that are transmitted through spores. Nosema infections in silkworms are diagnosed primarily through light microscopy, which is labour intensive and less reliable, sensitive, and specific than PCR-based techniques. Here, we present the development and optimization of a new TaqMan based assay targeting the β-tubulin gene in the pébrine disease causing agent Nosema bombycis in silkworms. The assay displayed excellent quantification linearity over multiple orders of magnitude of target amounts and a limit of detection (LOD) of 6.9 × 10 copies of target per reaction. The method is highly specific to N. bombycis with no cross-reactivity to other Nosema species commonly infecting wild silkworms. This specificity was due to three nucleotides in the probe-binding region unique to N. bombycis. The assay demonstrated a high reliability with a Coefficient of variation (CV) <5% for both intra-assay and inter-assay variability. The assay was used to trace experimental N. bombycis infection of silkworm larvae, in the fat body, midgut and ovary tissues, through pupation and metamorphosis to the emerging female moth, and her larval off-spring, confirming the vertical transmission of N. bombycis in silkworms. The TaqMan assay revealed a gradual increase in infection levels in the post-infection samples. The assay is reliable and simple to implement and can be a suitable complement to microscopy for routine diagnostics and surveillance in silkworm egg production centres with appropriate infrastructure.
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http://dx.doi.org/10.1016/j.mimet.2021.106238DOI Listing
May 2021

Availability, Formulation, Labelling, and Price of Low-Sodium Salts Worldwide.

JMIR Public Health Surveill 2021 May 13. Epub 2021 May 13.

The George Institute for Global Health, University of New South Wales, Sydney, AU.

Background: Regular salt is about 100% sodium chloride (NaCl). Low-sodium salts have reduced sodium chloride content, most commonly through substitution with potassium chloride (KCl). Low-sodium salts have a potential role in reducing population sodium intake level and blood pressure, but its availability in global market was unknown.

Objective: The aim of this study was to assess the availability, formulation, labelling, and price of low-sodium salts currently available to consumers around the world.

Methods: Low-sodium salts were identified through a systematic literature review, Google search, online shopping sites search, and inquiry of key informants. The keywords of "salt substitute", "low-sodium salt", "potassium salt", "mineral salt", and "sodium reduced salt" in six official languages of the United Nations were used for search. Information about the brand, formula, labelling, and price was extracted and analysed.

Results: Eighty-seven low-sodium salts were available in 47 out of 195 countries around the world (24%), including 28 high-income countries, 13 upper-middle-income countries, and six lower-middle-income countries. The proportion of sodium chloride varied from 0% (sodium-free) to 88% (as percent of weight, regular salt is 100% NaCl). Potassium chloride was the most frequent another component with levels ranging from 0% to 100% (potassium chloride salt). Forty-three (49%) had labels advising potential health risk, 33 (38%) labelling the advice of potential health benefits. The median price of low-sodium salts in high-income, upper-middle-income, lower-middle-income countries was USD 15.0/kg (IQR: 6.4 to 22.5), USD 2.7/kg (IQR: 1.7 to 5.5) and USD 2.9/kg (IQR: 0.50 to 22.2) respectively. The price of low-sodium salts was between 1.1 and 14.6 times that of regular salts.

Conclusions: Low-sodium salts are not widely available and are commonly more expensive than regular salts. Policies that promote the availability, affordability and labelling of low-sodium salts should enhance appropriate uptake for blood pressure lowering and cardiovascular prevention.

Clinicaltrial:

International Registered Report: RR2-10.1111/jch.14054.
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http://dx.doi.org/10.2196/27423DOI Listing
May 2021

Association between body mass index and blood pressure levels across socio-demographic groups and geographical settings: analysis of pooled data in Peru.

PeerJ 2021 21;9:e11307. Epub 2021 Apr 21.

CRONICAS Center of Excellence in Chronic Diseases, Universidad Peruana Cayetano Heredia, Lima, Peru.

Background: Understanding the relationship between BMI and blood pressure requires assessing whether this association is similar or differs across population groups. This study aimed to assess the association between body mass index (BMI) and blood pressure levels, and how these associations vary between socioeconomic groups and geographical settings.

Methods: Data from the National Demographic Health Survey of Peru from 2014 to 2019 was analyzed considering the complex survey design. The outcomes were levels of systolic (SBP) and diastolic blood pressure (DBP), and the exposure was BMI. Exposure and outcomes were fitted as continuous variables in a non-linear quadratic regression model. We explored effect modification by six socioeconomic and geographical variables (sex, age, education level, socioeconomic position, study area, and altitude), fitting an interaction term between each of these variables and BMI.

Results: Data from 159, 940 subjects, mean age 44.4 (SD: 17.1), 54.6% females, was analyzed. A third (34.0%) of individuals had ≥12 years of education, 24.7% were from rural areas, and 23.7% lived in areas located over 2,500 m above sea level. In the overall sample mean BMI was 27.1 (SD: 4.6) kg/m, and mean SBP and DBP were 122.5 (SD: 17.2) and 72.3 (SD: 9.8) mmHg, respectively. In the multivariable models, greater BMI levels were associated with higher SBP (-value < 0.001) and DBP (-value < 0.001). There was strong evidence that sex, age, education level, and altitude were effect modifiers of the association between BMI and both SBP and DBP. In addition to these socio-demographic variables, socioeconomic position and study area were also effect modifiers of the association between BMI and DBP, but not SBP.

Conclusions: The association between BMI and levels of blood pressure is not uniform on a range of socio-demographic and geographical population groups. This characterization can inform the understanding of the epidemiology and rise of blood pressure in a diversity of low-resource settings.
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http://dx.doi.org/10.7717/peerj.11307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067913PMC
April 2021

Effect of a Digital Intervention on Depressive Symptoms in Patients With Comorbid Hypertension or Diabetes in Brazil and Peru: Two Randomized Clinical Trials.

JAMA 2021 05;325(18):1852-1862

CRONICAS Center of Excellence in Chronic Diseases, Universidad Peruana Cayetano Heredia, Lima, Peru.

Importance: Depression is a leading contributor to disease burden globally. Digital mental health interventions can address the treatment gap in low- and middle-income countries, but the effectiveness in these countries is unknown.

Objective: To investigate the effectiveness of a digital intervention in reducing depressive symptoms among people with diabetes and/or hypertension.

Design, Setting, And Participants: Participants with clinically significant depressive symptoms (Patient Health Questionnaire-9 [PHQ-9] score ≥10) who were being treated for hypertension and/or diabetes were enrolled in a cluster randomized clinical trial (RCT) at 20 sites in São Paulo, Brazil (N=880; from September 2016 to September 2017; final follow-up, April 2018), and in an individual-level RCT at 7 sites in Lima, Peru (N=432; from January 2017 to September 2017; final follow-up, March 2018).

Interventions: An 18-session, low-intensity, digital intervention was delivered over 6 weeks via a provided smartphone, based on behavioral activation principles, and supported by nurse assistants (n = 440 participants in 10 clusters in São Paulo; n = 217 participants in Lima) vs enhanced usual care (n = 440 participants in 10 clusters in São Paulo; n = 215 participants in Lima).

Main Outcomes And Measures: The primary outcome was a reduction of at least 50% from baseline in PHQ-9 scores (range, 0-27; higher score indicates more severe depression) at 3 months. Secondary outcomes included a reduction of at least 50% from baseline PHQ-9 scores at 6 months.

Results: Among 880 patients cluster randomized in Brazil (mean age, 56.0 years; 761 [86.5%] women) and 432 patients individually randomized in Peru (mean age, 59.7 years; 352 [81.5%] women), 807 (91.7%) in Brazil and 426 (98.6%) in Peru completed at least 1 follow-up assessment. The proportion of participants in São Paulo with a reduction in PHQ-9 score of at least 50% at 3-month follow-up was 40.7% (159/391 participants) in the digital intervention group vs 28.6% (114/399 participants) in the enhanced usual care group (difference, 12.1 percentage points [95% CI, 5.5 to 18.7]; adjusted odds ratio [OR], 1.6 [95% CI, 1.2 to 2.2]; P = .001). In Lima, the proportion of participants with a reduction in PHQ-9 score of at least 50% at 3-month follow-up was 52.7% (108/205 participants) in the digital intervention group vs 34.1% (70/205 participants) in the enhanced usual care group (difference, 18.6 percentage points [95% CI, 9.1 to 28.0]; adjusted OR, 2.1 [95% CI, 1.4 to 3.2]; P < .001). At 6-month follow-up, differences across groups were no longer statistically significant.

Conclusions And Relevance: In 2 RCTs of patients with hypertension or diabetes and depressive symptoms in Brazil and Peru, a digital intervention delivered over a 6-week period significantly improved depressive symptoms at 3 months when compared with enhanced usual care. However, the magnitude of the effect was small in the trial from Brazil and the effects were not sustained at 6 months.

Trial Registration: ClinicalTrials.gov: NCT02846662 (São Paulo) and NCT03026426 (Lima).
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http://dx.doi.org/10.1001/jama.2021.4348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114139PMC
May 2021

Human-relevant near-organ neuromodulation of the immune system via the splenic nerve.

Proc Natl Acad Sci U S A 2021 May;118(20)

Clinical Sciences and Services, The Royal Veterinary College, Hatfield AL9 7TA, United Kingdom;

Neuromodulation of immune function by stimulating the autonomic connections to the spleen has been demonstrated in rodent models. Consequently, neuroimmune modulation has been proposed as a new therapeutic strategy for the treatment of inflammatory conditions. However, demonstration of the translation of these immunomodulatory mechanisms in anatomically and physiologically relevant models is still lacking. Additionally, translational models are required to identify stimulation parameters that can be transferred to clinical applications of bioelectronic medicines. Here, we performed neuroanatomical and functional comparison of the mouse, rat, pig, and human splenic nerve using in vivo and ex vivo preparations. The pig was identified as a more suitable model of the human splenic innervation. Using functional electrophysiology, we developed a clinically relevant marker of splenic nerve engagement through stimulation-dependent reversible reduction in local blood flow. Translation of immunomodulatory mechanisms were then assessed using pig splenocytes and two models of acute inflammation in anesthetized pigs. The pig splenic nerve was shown to locally release noradrenaline upon stimulation, which was able to modulate cytokine production by pig splenocytes. Splenic nerve stimulation was found to promote cardiovascular protection as well as cytokine modulation in a high- and a low-dose lipopolysaccharide model, respectively. Importantly, splenic nerve-induced cytokine modulation was reproduced by stimulating the efferent trunk of the cervical vagus nerve. This work demonstrates that immune responses can be modulated by stimulation of spleen-targeted autonomic nerves in translational species and identifies splenic nerve stimulation parameters and biomarkers that are directly applicable to humans due to anatomical and electrophysiological similarities.
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http://dx.doi.org/10.1073/pnas.2025428118DOI Listing
May 2021