The work-recovery cycle of kidney strain and inflammation in sugarcane workers following repeat heat exposure at work and at home.

Purpose: To examine heat exposure at work and home and the work-recovery cycle and temporal variation of kidney strain, muscle injury and inflammation biomarkers in sugarcane workers.

Methods: 20 male sugarcane workers (age: 33 ± 7 years) with a workplace Rest.Shade.

Effects on household income and earnings from chronic kidney disease of non-traditional origins: PREP project findings from Chichigalpa, Nicaragua.

Objective: Our purpose with this study is to examine the socioeconomic outcomes associated with chronic kidney disease not related to well-known risk factors (CKDnt) in four communities in Chichigalpa, Nicaragua that are home to a substantial number of sugarcane workers.

Methods: We employed a cluster-based systematic sampling design to identify differences in outcomes between those households affected directly by CKDnt and those that are not.

Results: Overall, we find that approximately one-third of households surveyed had a household member diagnosed with CKDnt.

Association Between Acute Kidney Injury Hospital Visits and Environmental Heat Stress at a Nicaraguan Sugarcane Plantation.

Background: Mesoamerican sugarcane cutters are at a high risk of chronic kidney disease of non-traditional origin, a disease likely linked to heat-related acute kidney injury (AKI). Studies in general populations have described a positive association between high environmental temperatures and clinically assessed kidney outcomes, but there are no studies in occupational settings.

Method: We accessed routine records of clinically diagnosed AKI (AKI-CD) and wet bulb globe temperatures (WBGT) at a large Nicaraguan sugarcane plantation and modeled the relationship between these using negative binomial regression.

Impact of heat and a rest-shade-hydration intervention program on productivity of piece-paid industrial agricultural workers at risk of chronic kidney disease of nontraditional origin.

Objectives: Assess the impact of environmental heat and a rest-shade-hydration (RSH) intervention against heat stress on productivity of piece-paid Mesoamerican sugarcane cutters. These workers are at a high risk of chronic kidney disease of non-traditional origin (CKDnt), from the severe heat stress they experience due to heavy work under hot conditions. RSH interventions in these populations improve kidney health outcomes, but their impact on productivity has yet to be examined.

Semisynthetic polymyxins with potent antibacterial activity and reduced kidney cell toxicity.

The growing incidence of infections caused by multi-drug resistant Gram-negative bacteria has led to an increased use of last-resort antibiotics such as the polymyxins. Polymyxin therapy is limited by toxicity concerns, most notably nephrotoxicity. Recently we reported the development of a novel class of semisynthetic polymyxins with reduced toxicity wherein the N-terminal lipid and diaminobutyric acid residue are replaced by a cysteine-linked lipid featuring a reductively labile disulfide bond.

Nonchromosomal birth defects and risk of childhood acute leukemia: An assessment in 15 000 leukemia cases and 46 000 controls from the Childhood Cancer and Leukemia International Consortium.

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia.

Point-of-care biomarkers for prediction of kidney function trajectory among sugarcane cutters: a comparative test accuracy study.

Objectives: Heat-stressed Mesoamerican workers, such as sugarcane cutters, suffer from high rates of chronic kidney disease of non-traditional origin (CKDnt). We aimed to identify easily available early markers of rapid kidney function decline in a population at high risk of CKDnt.

Design: The accuracy of different biomarkers measured during harvest for prediction of cross-harvest kidney function decline were assessed in an exploratory study group, and the performance of the most promising biomarker was then assessed in an independent confirmation group.

Synthesis and Evaluation of Polymyxins Bearing Reductively Labile Disulfide-Linked Lipids.

Polymyxins are a class of lipopeptide anti-infective agents with potent and specific activity against Gram-negative bacteria. While toxicity concerns associated with polymyxin B and E (colistin) have historically limited their clinical application, today they are increasingly used as last-resort antibiotics given the rise of multidrug-resistant Gram-negative pathogens. The adverse side effects of polymyxins are well known, particularly as related to their nephrotoxicity.

Polymyxin Stereochemistry and Its Role in Antibacterial Activity and Outer Membrane Disruption.

With increasing rates of resistance toward commonly used antibiotics, especially among Gram-negative bacteria, there is renewed interested in polymyxins. Polymyxins are lipopeptide antibiotics with potent anti-Gram-negative activity and are generally believed to target lipid A, the lipopolysaccharide (LPS) anchor found in the outer membrane of Gram-negative bacteria. To characterize the stereochemical aspects of their mechanism(s) of action, we synthesized the full enantiomers of polymyxin B and the polymyxin B nonapeptide (PMBN).

Synthesis and Structure-Activity Studies of β-Barrel Assembly Machine Complex Inhibitor MRL-494.

In the hunt for new antibiotics with activity against Gram-negative pathogens, the outer membrane β-barrel assembly machine (BAM) complex has become an increasingly interesting target. The recently reported BAM complex inhibitor, MRL-494, was discovered via a screening campaign for molecules that target the outer membrane. Notably, MRL-494 was reported to be an unintended byproduct generated during the synthesis of an unrelated compound, and as such no synthesis of the compound was disclosed.

Targeting workload to ameliorate risk of heat stress in industrial sugarcane workers.

Objective: The aim of this study was to quantify the physiological workload of manual laborers in industrial sugarcane and assess the effect of receiving a rest, shade, and hydration intervention to reduce heat stress exposure risk.

Methods: In an observational study, physiological workload was evaluated for burned cane cutters (BCC), seed cutters (SC) and drip irrigation repair workers (DIRW) using heart rate (HR) recorded continuously (Polar®) across a work shift. Workers' percentage of maximal HR (%HR), time spent in different HR zones, and estimated core temperature (ECTemp) were calculated.

Synergy by Perturbing the Gram-Negative Outer Membrane: Opening the Door for Gram-Positive Specific Antibiotics.

New approaches to target antibacterial agents toward Gram-negative bacteria are key, given the rise of antibiotic resistance. Since the discovery of polymyxin B nonapeptide as a potent Gram-negative outer membrane (OM)-permeabilizing synergist in the early 1980s, a vast amount of literature on such synergists has been published. This Review addresses a range of peptide-based and small organic compounds that disrupt the OM to elicit a synergistic effect with antibiotics that are otherwise inactive toward Gram-negative bacteria, with synergy defined as a fractional inhibitory concentration index (FICI) of <0.

Synthetic studies with the brevicidine and laterocidine lipopeptide antibiotics including analogues with enhanced properties and efficacy.

Brevicidine and laterocidine are two recently discovered lipopeptide antibiotics with promising antibacterial activity. Possessing a macrocyclic core, multiple positive charges, and a lipidated N-terminus, these lipopeptides exhibit potent and selective activity against Gram-negative pathogens, including polymyxin-resistant isolates. Given the low amounts of brevicidine and laterocidine accessible by fermentation of the producing microorganisms, synthetic routes to these lipopeptides present an attractive alternative.

Workplace Intervention for Heat Stress: Essential Elements of Design, Implementation, and Assessment.

Heat stress is associated with numerous health effects that potentially harm workers, especially in a warming world. This investigation occurred in a setting where laborers are confronted with occupational heat stress from physically demanding work in high environmental temperatures. Collaboration with a major Nicaraguan sugarcane producer offered the opportunity to study interventions to prevent occupational heat-stress-related kidney disease.

Markers of kidney tubular and interstitial injury and function among sugarcane workers with cross-harvest serum creatinine elevation.

Objectives: Serum creatinine (SCr) is a routine marker of kidney injury but also increases with dehydration and muscular work. This study was to elucidate whether increase in SCr is associated with more specific markers of kidney tubular and interstitial injury and function, during prolonged heat stress among workers at high risk of chronic kidney disease of non-traditional origin (CKDnt).

Methods: Urine monocyte chemoattractant protein-1 (MCP-1), kidney injury molecule-1 (KIM-1), calbindin, glutathione S-transferase-π (GST-π), clusterin, interleukin 18 and albumin, fractional excretion of potassium (FEK), blood haemoglobin, serum potassium, ferritin and erythropoietin were measured before and after harvest in a sample of 30 workers with a ≥0.

Structure-Activity Studies with Bis-Amidines That Potentiate Gram-Positive Specific Antibiotics against Gram-Negative Pathogens.

Pentamidine, an FDA-approved antiparasitic drug, was recently identified as an outer membrane disrupting synergist that potentiates erythromycin, rifampicin, and novobiocin against Gram-negative bacteria. The same study also described a preliminary structure-activity relationship using commercially available pentamidine analogues. We here report the design, synthesis, and evaluation of a broader panel of bis-amidines inspired by pentamidine.

Thrombin-Derived Peptides Potentiate the Activity of Gram-Positive-Specific Antibiotics against Gram-Negative Bacteria.

The continued rise of antibiotic resistance threatens to undermine the utility of the world's current antibiotic arsenal. This problem is particularly troubling when it comes to Gram-negative pathogens for which there are inherently fewer antibiotics available. To address this challenge, recent attention has been focused on finding compounds capable of disrupting the Gram-negative outer membrane as a means of potentiating otherwise Gram-positive-specific antibiotics.

Prevalence Studies on CKDu Need Stringent Reporting on Outcomes to Enhance Comparability.

Prevalence studies on Chronic Kidney Disease of unknown etiology (CKDu) need stringent reporting on outcomes following existing guidelines. Only by doing so, the much-needed comparisons between occupations, regions and climates for the elucidation of the etiology/etiologies of CKDu, and subsequently for its prevention, are possible. We, here, comment on methodological issues in a recently published study on rice farmers from West Java, Indonesia.

Pesticide risk perceptions among bystanders of aerial spraying on bananas in Costa Rica.

Little is known about how bystanders perceive risks from pesticide use in areas with frequent aerial spraying of pesticides. This research aims to better understand how bystanders (school workers) from three counties of the Limón province in Costa Rica, who did not have a contractual relationship with agricultural production, perceive risks of pesticides in the areas where they work and live. A face-to-face survey was carried out among 475 school workers, of whom 455 completed all 33 questions on pesticide risk perception.

Pathophysiological Mechanisms by which Heat Stress Potentially Induces Kidney Inflammation and Chronic Kidney Disease in Sugarcane Workers.

Background: Chronic kidney disease of non-traditional origin (CKDnt) is common among Mesoamerican sugarcane workers. Recurrent heat stress and dehydration is a leading hypothesis. Evidence indicate a key role of inflammation.

Preventing kidney injury among sugarcane workers: promising evidence from enhanced workplace interventions.

Objectives: To assess if improvement of working conditions related to heat stress was associated with improved kidney health outcomes among sugarcane harvest workers in Chichigalpa, Nicaragua, a region heavily affected by the epidemic of chronic kidney disease of non-traditional origin.

Methods: Based on our findings during the 2017-2018 harvest (harvest 1), recommendations that enhanced the rest schedule and improved access to hydration and shade were given before the 2018-2019 harvest (harvest 2). Actual work conditions during harvest 2 were then observed.

Chronic kidney disease of non-traditional origin in Mesoamerica: a disease primarily driven by occupational heat stress.

The death toll of the epidemic of chronic kidney disease of nontraditional origin (CKDnt) in Mesoamerica runs into the tens of thousands, affecting mostly young men. There is no consensus on the etiology. Anecdotal evidence from the 1990s pointed to work in sugarcane; pesticides and heat stress were suspected.

Early immune stimulation and childhood acute lymphoblastic leukemia in Costa Rica: A comparison of statistical approaches.

Background: Although epidemiologic studies suggest that early immune stimulation is protective against childhood leukemia, evidence for this relationship is equivocal for Hispanic children, who are disproportionately affected by this disease. The complex biological processes underlying immune stimulation and leukemogenesis may benefit from novel statistical approaches that account for mixed exposures and their nonlinear interactions. In this study, we utilized targeted machine learning and traditional statistical methods to investigate the association of multiple measures of early immune stimulation with acute lymphoblastic leukemia (ALL) in Costa Rican children.