Toxicological Effects of Inhaled Crude Oil Vapor.

PURPOSE OF REVIEW: The purpose of this review is to assess the toxicological consequences of crude oil vapor (COV) exposure in the workplace through evaluation of the most current epidemiologic and laboratory-based studies in the literature. RECENT FINDINGS: Crude oil is a naturally occuring mixture of hydrocarbon deposits, inorganic and organic chemical compounds. Workers engaged in upstream processes of oil extraction are exposed to a number of risks and hazards, including getting crude oil on their skin or inhaling crude oil vapor. There have been several reports of workers who died as a result of inhalation of high levels of COV released upon opening thief hatches atop oil storage tanks. Although many investigations into the toxicity of specific hydrocarbons following inhalation during downstream oil processing have been conducted, there is a paucity of information on the potential toxicity of COV exposure itself. This review assesses current knowledge of the toxicological consequences of exposures to COV in the workplace.

Biological effects of inhaled crude oil vapor V. Altered biogenic amine neurotransmitters and neural protein expression.

Workers in the oil and gas industry are at risk for exposure to a number of physical and chemical hazards at the workplace. Chemical hazard risks include inhalation of crude oil or its volatile components. While several studies have investigated the neurotoxic effects of volatile hydrocarbons, in general, there is a paucity of studies assessing the neurotoxicity of crude oil vapor (COV). Consequent to the 2010 Deepwater Horizon (DWH) oil spill, there is growing concern about the short- and long-term health effects of exposure to COV. NIOSH surveys suggested that the DWH oil spill cleanup workers experienced neurological symptoms, including depression and mood disorders, but the health effects apart from oil dispersants were difficult to discern. To investigate the potential neurological risks of COV, male Sprague-Dawley rats were exposed by whole-body inhalation to COV (300 ppm; Macondo surrogate crude oil) following an acute (6 h/d × 1 d) or sub-chronic (6 h/d × 4 d/wk. × 4 wks) exposure regimen. At 1, 28 or 90 d post-exposure, norepinephrine (NE), epinephrine (EPI), dopamine (DA) and serotonin (5-HT) were evaluated as neurotransmitter imbalances are associated with psychosocial-, motor- and cognitive- disorders. Sub-chronic COV exposure caused significant reductions in NE, EPI and DA in the dopaminergic brain regions, striatum (STR) and midbrain (MB), and a large increase in 5-HT in the STR. Further, sub-chronic exposure to COV caused upregulation of synaptic and Parkinson's disease-related proteins in the STR and MB. Whether such effects will lead to neurodegenerative outcomes remain to be investigated.

Antioxidant micronutrient supplements for adult critically ill patients: A bayesian multiple treatment comparisons meta-analysis.

BACKGROUND & AIMS: Antioxidant micronutrients (AxMs) have been administered to critically ill adults attempting to counteract the oxidative stress imposed during critical illness. However, results are conflicting and relative effectiveness of AxMs regimens is unknown. We conducted a Bayesian multi-treatment comparison (MTC) meta-analysis to identify the best AxM treatment regimen that will improve clinical outcomes. METHODS: PubMed, EMBASE, Web of Science and Cochrane databases were searched from the inception of databases through August 2020. Randomized controlled trials (RCT) comparing AxMs supplementations with placebo among critically ill adults were included. Two authors assessed trial quality using Cochrane risk of bias tool and assessed certainty of evidence (CoE). A random effect model, non-informative priors Bayesian MTC meta-analysis using gemtc package in R version 3.6.2 was performed. AxMs treatment effect on clinical outcomes (mortality, infection rates, intensive care unit (ICU) and hospital stays and ventilator days) were represented by absolute risk differences (ARD) for dichotomous outcomes and mean differences (MD) for continuous outcomes. Prior to final analysis, we repeated the search through January 2021. RESULTS: 37 RCT (4905 patients) were included with 16 direct comparisons. With respect to mortality, the ARD for "vitamin E" compared with placebo was centred at -0.19 [95%CrI: -0.54,0.16; very low CoE] and was ranked the best treatment for mortality reduction as per surface under the cumulative ranking curve (SUCRA 0.71, 95%CrI: 0.07,1.00). A combination of "selenium, zinc and copper" was ranked the best for lowest ICU stay [-9.40, 95% CrI: -20.0,1.50; low CoE]. A combination of "selenium, zinc, copper and vitamin E" was ranked the best treatment for infection risk reduction [-0.22, 95% CrI: -0.61,0.17; very low CoE]. Ventilator days were least with a combination of "selenium, zinc and manganese" [2.80, 95% CrI: -6.30,0.89; low CoE]. Hospital stay was the lowest using a combination of "selenium, zinc and copper" [-13.00, 95% CrI: -38.00,13.00; very low CoE]. There is substantial uncertainty present in the rankings due to wide and overlapping 95% CrIs of SUCRA scores for the treatments. CONCLUSIONS: Studies on critically ill adult patients have suggested a possible beneficial effects of certain AxM supplementations over and above the recommended dietary allowance. However, evidence does not support their use in clinical practice due to the low confidence in the estimates. Current studies evaluating specific AxMs or their combinations are limited with small sample sizes. REGISTRATION: PROSPERO, CRD42020210199. TAKE-HOME MESSAGE: Evidence suggesting a potential benefit of AxMs use more than recommended doses in critically ill adults is weak, indicating that there is no justification for this practice.

Biological effects of inhaled hydraulic fracturing sand dust VII. Neuroinflammation and altered synaptic protein expression.

Hydraulic fracturing (fracking) is a process used to recover oil and gas from shale rock formation during unconventional drilling. Pressurized liquids containing water and sand (proppant) are used to fracture the oil- and natural gas-laden rock. The transportation and handling of proppant at well sites generate dust aerosols; thus, there is concern of worker exposure to such fracking sand dusts (FSD) by inhalation. FSD are generally composed of respirable crystalline silica and other minerals native to the geological source of the proppant material. Field investigations by NIOSH suggest that the levels of respirable crystalline silica at well sites can exceed the permissible exposure limits. Thus, from an occupational safety perspective, it is important to evaluate the potential toxicological effects of FSD, including any neurological risks. Here, we report that acute inhalation exposure of rats to one FSD, i.e., FSD 8, elicited neuroinflammation, altered the expression of blood brain barrier-related markers, and caused glial changes in the olfactory bulb, hippocampus and cerebellum. An intriguing observation was the persistent reduction of synaptophysin 1 and synaptotagmin 1 proteins in the cerebellum, indicative of synaptic disruption and/or injury. While our initial hazard identification studies suggest a likely neural risk, more research is necessary to determine if such molecular aberrations will progressively culminate in neuropathology/neurodegeneration leading to behavioral and/or functional deficits.

A Comprehensive Nutrition-Focused Quality Improvement Program Reduces 30-Day Readmissions and Length of Stay in Hospitalized Patients.

BACKGROUND: Although screening patients for malnutrition risk on hospital admission is standard of care, nutrition shortfalls are undertreated. Nutrition interventions can improve outcomes. We tested effects of a nutrition-focused quality improvement program (QIP) on hospital readmission and length of stay (LOS). MATERIALS AND METHODS: QIP included malnutrition risk screening at admission, prompt initiation of oral nutrition supplements (ONS) for at-risk patients, and nutrition support. A 2-group, pre-post design of malnourished adults with any diagnosis was conducted at 4 hospitals: QIP-basic (QIPb) and QIP-enhanced (QIPe). Comparator patients had a malnutrition diagnosis and ONS orders. For QIPb, nurses screened all patients on admission using an electronic medical record (EMR)-cued Malnutrition Screening Tool (MST); ONS was provided to patients with MST scores ≥2 within 24-48 hours. QIPe had ONS within 24 hours, postdischarge nutrition instructions, telephone calls, and ONS coupons. Primary outcome was 30-day unplanned readmission. We used baseline (January 1-December 31, 2013) and validation cohorts (October 13, 2013-April 2, 2014) for comparison. RESULTS: Patients (n = 1269) were enrolled in QIPb (n = 769) and QIPe (n = 500). Analysis included baseline (n = 4611) and validation (n = 1319) comparator patients. Compared with a 20% baseline readmission rate, post-QIP relative reductions were 19.5% for all QIP, 18% for QIPb, and 22% for QIPe, respectively. Compared with a 22.1% validation readmission rate, relative reductions were 27.1%, 25.8%, and 29.4%, respectively. Similar reductions were noted for LOS. CONCLUSIONS: Thirty-day readmissions and LOS were significantly lowered for malnourished inpatients by use of an EMR-cued MST, prompt provision of ONS, patient/caregiver education, and sustained nutrition support.

The relationship between immediate preoperative serum 25-hydroxy-vitamin D3 levels and cardiac function, dysglycemia, length of stay, and 30-d readmissions in cardiac surgery patients.

OBJECTIVES: Vitamin D has pleiotropic effects on cardiac, renal, and endocrine diseases like diabetes mellitus and deficiency has been correlated with increased Intensive Care Unit (ICU) morbidity and mortality. We studied the relationship between preoperative Vitamin D levels and several short-term endpoints including cardiovascular events, glucose levels, ICU, and hospital length of stay. METHODS: Standard demographic data were obtained. Blood samples were drawn for 25-hydroxy-vitamin D3 (Vit D) levels at baseline (just before induction of anesthesia) and on postoperative day (POD #1). The number of inotropes used on POD # 0, 1, and 2 was recorded as well as the Cardiac Index (CI). Baseline glucose, Blood Urea Nitrogen and Creatinine (Cr) levels were obtained and repeated on POD # 1 & 2. Other variables studied are number of days of ICU and hospital stay. RESULTS: Of the 64 patients included in the cohort, 3 were excluded because of inadequate data. 69% had Vit D levels <20 ng/mL and 31% had levels ≥20 ng/mL. More than 90% of the cohort had a significant decrease in POD # 1 Vit D levels (P < 0.001). Age, sex, race, and body mass index did not predict the preoperative Vit D levels; however, the timing of surgery was associated with preoperative Vit D levels, lowest in subjects who had surgery performed during winter. Preoperative Vit D levels had no effect on postoperative glycemic control, cardiac index, or composite outcome-arrhythmias, respiratory failure, or prolonged inotropic support. On regression analysis, preoperative Vit D levels did show a significant effect on ICU and hospital length of stay in this cohort. CONCLUSIONS: The low levels in this study truly represent the Vit D status as they were obtained before any intervention, including surgery or fluid administration. Vit D levels decreased rapidly after surgery and hence future studies on Vit D may need to focus on premorbid levels obtained at the time of initial presentation and not those obtained after resuscitation or ICU admission. In contrast to epidemiologic reports, we found no association between low Vit D levels and postoperative cardiovascular events. However, low Vit D levels did affect the ICU and hospital length of stay in patients who were undergoing cardiac surgery. This is an important finding especially when many institutions and regulatory agencies are investigating novel therapies and processes to reduce the length of hospitalization. More studies are required to investigate the effect on hospital length of stay of early preadmission or preoperative Vit D supplementation before elective surgery.

Thiamine in nutrition therapy.

Clinicians involved with nutrition therapy traditionally concentrated on macronutrients and have generally neglected the importance of micronutrients, both vitamins and trace elements. Micronutrients, which work in unison, are important for fundamental biological processes and enzymatic reactions, and deficiencies may lead to disastrous consequences. This review concentrates on vitamin B(1), or thiamine. Alcoholism is not the only risk factor for thiamine deficiency, and thiamine deficiency is often not suspected in seemingly well-nourished or even overnourished patients. Deficiency of thiamine has historically been described as beriberi but may often be seen in current-day practice, manifesting as neurologic abnormalities, mental changes, congestive heart failure, unexplained metabolic acidosis, and so on. This review explains the importance of thiamine in nutrition therapy and offers practical tips on prevention and management of deficiency states.

Update on micronutrients in bariatric surgery.

PURPOSE OF REVIEW: Obesity is a growing worldwide epidemic. Obese patients are often deficient in micronutrients despite macronutrient excess. Bariatric surgery is an increasingly utilized modality in the treatment of obesity and obesity-related conditions. Bariatric surgery itself may cause or exacerbate micronutrient deficiencies with serious sequelae. This review will focus on perioperative strategies to detect, prevent and treat micronutrient deficiencies in patients undergoing bariatric surgery, and will highlight practical and clinical aspects of these nutritional problems. RECENT FINDINGS: Micronutrient deficiency is common in obese patients undergoing bariatric surgery both preoperatively and postoperatively. Bariatric procedures with a malabsorptive component are more likely to result in postoperative micronutrient deficiency. A system-based approach will facilitate clinical suspicion of specific or combined micronutrient deficiencies, leading to appropriate laboratory tests for confirmation. Supplementation by the oral route is always tried first, reserving parenteral administration for specific situations. SUMMARY: Clinicians should be aware that micronutrient deficiencies are common in obese patients who may have macronutrient excess. Micronutrient deficiency may exist preoperatively or be caused by bariatric procedures themselves. A systematic and team-based approach will decrease morbidity associated with delays in diagnosis and treatment.

Micronutrient deficiencies after bariatric surgery.

It has been estimated that approximately 220,000 people with morbid obesity underwent bariatric surgery in 2008. Modification of the gastrointestinal tract affects absorption and health care professionals counseling bariatric patients need to be aware of possible micronutrient deficiencies and their symptoms. A systematic review of several databases and bariatric surgery center websites on the Internet was conducted from January 1980 to July 2009 to identify literature related to micronutrient deficiencies occurring after bariatric surgery. Keywords used individually or in combination were bariatric surgery, obesity, vitamin/mineral deficiencies, altered gastrointestinal function, nutrient absorption, nutrient supplementation, and metabolic complications, and were variously combined in the search list. Based on this review, all patients scheduled for bariatric surgery should receive daily multivitamin and multitrace mineral supplements. The literature suggests that bariatric surgery patients are at risk for deficiency of the following nutrients after surgery: vitamins B(12), B(1), C, folate, A, D, and K, along with the trace minerals iron, selenium, zinc, and copper. Over-the-counter multivitamin and mineral supplements do not provide adequate amounts of certain nutrients such as vitamin B(12), iron, or fat-soluble vitamins and patients will require additional doses of prophylactic supplementation life-long to maintain optimal micronutrient status. In addition, preconception care for adequate prenatal supplementation is critical for pregnant women who have undergone bariatric surgery, as iron, vitamin A, vitamin B(12), vitamin K, and folate deficiencies are associated with maternal and fetal complications, including severe anemia, congenital abnormalities, low birth weight, and failure to thrive. All bariatric surgery patients would be best served by receiving regular monitoring of serum nutrient levels starting at 3 mo after surgery and periodically thereafter.

Refeeding syndrome: treatment considerations based on collective analysis of literature case reports.

Refeeding syndrome (RFS) represents a group of clinical findings that occur in severely malnourished individuals undergoing nutritional support. Cardiac arrhythmias, multisystem organ dysfunction, and death are the most severe symptoms observed. As the cachectic body attempts to reverse its adaptation to the starved state in response to the nutritional load, symptoms result from fluid and electrolyte imbalances, with hypophosphatemia playing a central role. Because guidelines for feeding the malnourished patient at risk for refeeding syndrome is scarce, we have provided management recommendations based on the knowledge derived from a collection of reported English literature cases of the RFS. A MEDLINE search using keywords including "refeeding syndrome," "RFS," and "refeeding hypophosphatemia" was performed. References from initial cases were utilized for more literature on the subject. We have emphasized the continued importance of managing patients at risk for RFS, compared how management of the severely malnourished patients have evolved over time, and provided comprehensive clinical guidelines based on the sum of experience documented in the case reports for the purpose of supplementing the guidelines available. Based on our review, the most effective means of preventing or treating RFS were the following: recognizing the patients at risk; providing adequate electrolyte, vitamin, and micronutrient supplementation; careful fluid resuscitation; cautious and gradual energy restoration; and monitoring of critical laboratory indices.

Micronutrient supplementation in adult nutrition therapy: practical considerations.

Preexisting micronutrient (vitamins and trace elements) deficiencies are often present in hospitalized patients. Deficiencies occur due to inadequate or inappropriate administration, increased or altered requirements, and increased losses, affecting various biochemical processes and resulting in organ dysfunction, poor wound healing, and altered immune status with deleterious sequelae. Guidelines for the 13 essential vitamins and 10 essential trace elements have been established. These recommendations, however, are applicable to healthy adults and not to critically ill patients, in whom decreased serum levels may indicate actual deficiencies or a deficiency due to redistribution. Benefits of supplementation over and above the daily requirements, which may not result in increased serum levels, are also unclear and may, in fact, be detrimental. Vitamin requirements are increased in disease states, but a similar recommendation for trace elements has not been initiated except for selenium (Se) and zinc (Zn). In practice, a multivitamin preparation and a multiple trace element admixture (containing Zn, Se, copper, chromium, and manganese) are added to parenteral nutrition formulations. Most enteral nutrition preparations also contain adequate amounts of vitamins and trace elements, although bioavailability may be an issue. Detailed information about individual micronutrient use specifically in hospitalized adult patients receiving nutrition therapy will be discussed, emphasizing the practical and clinical aspects. Clinicians are encouraged to think of micronutrients not as nutritional supplements alone but also as therapeutic agents and nutraceuticals.

Glial fibrillary acidic protein and related glial proteins as biomarkers of neurotoxicity.

A variety of '-omic' technologies are being increasingly applied in preclinical safety assessments. Such approaches, however, have not been implemented in neurotoxicity safety evaluations. Current regulatory guidelines for assessing neurotoxicity emphasise reliance on traditional histopathological stains and behavioural testing batteries. Although these methods may be sufficient to detect some neurotoxic effects, they lack both the sensitivity and specificity required for broad-scale neurotoxicity screening. The glial reaction to nervous system damage, often termed gliosis, represents a hallmark of all types of nervous system injury. As such, the development and implementation of gliosis biomarkers represents a broadly applicable approach for neurotoxicity safety assessment. Using a panel of known neurotoxic agents, the authors have shown that the astroglial protein, glial fibrillary acidic protein (GFAP), can serve as one such biomarker of neurotoxicity. Qualitative and quantitative analysis of GFAP has shown this biomarker to be a sensitive and specific indicator of the neurotoxic condition. The implementation of GFAP and related glial biomarkers in neurotoxicity screens may serve as the basis for further development of molecular signatures predictive of adverse effects on the nervous system.

Induction of gp130-related cytokines and activation of JAK2/STAT3 pathway in astrocytes precedes up-regulation of glial fibrillary acidic protein in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of neurodegeneration: key signaling pathway for astrogliosis in vivo?

Reactive gliosis is a hallmark of disease-, trauma-, and chemical-induced damage to the central nervous system. The signaling pathways associated with this response to neural injury remain to be elucidated, but recent evidence implicates the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway. Here, we used the known dopaminergic neurotoxicant, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), to selectively damage striatal dopaminergic nerve terminals and elicit a glial response. We then analyzed changes in gene expression and protein phosphorylation, in vivo, to identify ligands and mediators of the JAK-STAT pathway that accompany glial activation. Administration of MPTP caused rapid tyrosine (Tyr-705) phosphorylation and nuclear translocation of STAT3 in striatal astrocytes, prior to the induction of glial fibrillary acidic protein mRNA and protein. Pharmacological protection of dopaminergic nerve terminals with nomifensine abolished MPTP-mediated phosphorylation and translocation of STAT3 and prevented induction of astrogliosis. Among the Janus kinase family of tyrosine kinases, only JAK2 was associated with the phosphorylation of STAT3 after MPTP and, inhibition of JAK2 by AG490, in vivo, attenuated both the phosphorylation of STAT3 and induction of GFAP. The p44/42 mitogen-activated protein kinase (MAPK; ERK1/2) also was activated by MPTP, but was not associated with activation of STAT3, because serine (Ser-727) was not phosphorylated. The mRNA for ligands of the gp130-JAK/STAT3 signaling pathway, interleukin-6, leukemia inhibitory factor, and oncostatin M were elevated prior to activation of STAT3 and induction of astrogliosis; neuroprotection with nomifensine blocked these effects of MPTP. Taken together, our results suggest that the gp130-mediated activation of JAK2/STAT3 signaling pathway may play a key role in the induction of astrogliosis.