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Noncommunicable diseases (NCDs) are the leading cause of death in the world, and 80% of all NCD deaths occur in low- and middle-income countries (LMICs). The COVID-19 pandemic has demonstrated that patients with NCDs are at increased risk of becoming severely ill from the virus. Disproportionate investment in vertical health programs can result in health systems vulnerable to collapse when resources are strained, such as during pandemics. Although NCDs are largely preventable, globally there is underinvestment in efforts to address them. Integrating health systems to collectively address NCDs and infectious diseases through a wide range of services in a comprehensive manner reduces the economic burden of healthcare and strengthens the healthcare system. Health system resiliency is essential for health security. In this article, we provide an economically sound approach to incorporating NCDs into routine healthcare services in LMICs through improved alignment of institutions that support prevention and control of both NCDs and infectious diseases. Examples from Zambia's multisector interventions to develop and support a national NCD action plan can inform and encourage LMIC countries to invest in systems integration to reduce the social and economic burden of NCDs and infectious diseases.

The aim of this study is to capture the dental anxiety of patients in a dental clinic. A special focus was placed on the measurement of the course of possible anxiety occurring during a single dental visit with different surgical procedures. Therefore, 129 patients were interviewed in an oral surgical clinic. The course of possible anxiety was measured with a short questionnaire about the current stress (“Kurzfragebogen zur aktuellen Beanspruchung”, KAB), which was completed by the patients at three different times in the waiting room, as well as before and after the treatment in the consulting room. In the waiting room, the patient answered a questionnaire, including the following instruments: questions about age and sex, KAB (stress), and the Dental Anxiety Scale (DAS, anxiety). According to the DAS, 64.1% belonged to the low-anxiety group, 29.7% belonged to the medium-anxiety group and 6.2% belonged to the high-anxiety group. For all groups, the stress just before the treatment was the highest and it was the lowest after treatment. The KAB values of the female patients were significantly higher than those of the male patients. About one third of the patients suffered from dental anxiety.

The temporomandibular joint (TMJ) is a specialized synovial joint that is crucial for the movement and function of the jaw. TMJ osteoarthritis (TMJ OA) is the result of disc dislocation, trauma, functional overburden, and developmental anomalies. TMJ OA affects all joint structures, including the articular cartilage, synovium, subchondral bone, capsule, ligaments, periarticular muscles, and sensory nerves that innervate the tissues. The present review aimed to illustrate the main pathomechanisms involving cartilage and bone changes in TMJ OA and some therapeutic options that have shown potential restorative properties regarding these joint structures in vivo. Chondrocyte loss, extracellular matrix (ECM) degradation, and subchondral bone remodeling are important factors in TMJ OA. The subchondral bone actively participates in TMJ OA through an abnormal bone remodeling initially characterized by a loss of bone mass, followed by reparative mechanisms that lead to stiffness and thickening of the condylar osteochondral interface. In recent years, such therapies as intraarticular platelet-rich plasma (PRP), hyaluronic acid (HA), and mesenchymal stem cell-based treatment (MSCs) have shown promising results with respect to the regeneration of joint structures or the protection against further damage in TMJ OA. Nevertheless, PRP and MSCs are more frequently associated with cartilage and/or bone repair than HA. According to recent findings, the latter could enhance the restorative potential of other therapies (PRP, MSCs) when used in combination, rather than repair TMJ structures by itself. TMJ OA is a complex disease in which degenerative changes in the cartilage and bone develop through intricate mechanisms. The regenerative potential of such therapies as PRP, MSCs, and HA regarding the cartilage and subchondral bone (alone or in various combinations) in TMJ OA remains a matter of further research, with studies sometimes obtaining discrepant results.

Short-term in vitro genotoxicity assays are useful tools to assess whether new and emerging tobacco products potentially have reduced toxicity. We previously demonstrated that potency ranking by benchmark dose (BMD) analysis quantitatively identifies differences among several known carcinogens and toxic chemicals representing different chemical classes found in cigarette smoke. In this study, six whole smoke solution (WSS) samples containing both the particulate and gas phases of tobacco smoke were generated from two commercial cigarette brands under different smoking-machine regimens. Sixty test cigarettes of each brand were machine-smoked according to the International Organization for Standardization (ISO) puffing protocol. In addition, either 60 or 20 test cigarettes of each brand were machine-smoked with the Canadian Intense (CI) puffing protocol. All six WSSs were evaluated in the bacterial reverse mutation (Ames) test using Salmonella typhimurium strains, in the presence or absence of S9 metabolic activation. The resulting S9-mediated mutagenic concentration–responses for the four WSSs from 60 cigarettes were then compared using BMD modelling analysis and the mutagenic potency expressed as number of revertants per μl of the WSS. The quantitative approaches resulted in a similar rank order of mutagenic potency for the Ames test in both TA98 and TA100. Under the conditions of this study, these results indicate that quantitative analysis of the Ames test data can discriminate between the mutagenic potencies of WSSs on the basis of smoking-machine regimen (ISO vs. CI), and cigarette product (differences in smoke chemistry).

Systemic lupus erythematosus (SLE), the prototype autoimmune disease, is characterized by the production of a plethora of autoantibodies with various roles in the development of disease-related tissue damage. C-reactive protein (CRP) is an acute phase reactant with a pentameric structure. Under acidic or alkaline conditions, or when urea levels are high and/or calcium levels are low, the pentamer (pCRP) dissociates irreversibly into monomeric CRP (mCRP) and exposes new epitopes (neo-CRP). Importantly, anti-mCRP (but not anti-pCRP) antibodies have been described in patients with SLE, their prevalence varying from 4% to 78% in different cohorts. Numerous studies have investigated the relationship between autoantibodies directed against CRP (anti-CRP) and disease activity as well as their association with lupus nephritis (LN), frequently reporting discrepant findings. The main objective of the present review is to describe the role of anti-mCRP antibodies in SLE according to the currently available data.

Systemic sclerosis (SSc) is a rare autoimmune disease characterized by widespread microvasculopathy, inflammation, and fibrosis of the skin and internal organs. The involvement of the gastrointestinal tract is associated with a wide variety of symptoms and affects circa 90% of patients during the course of the disease. The gastrointestinal microbiota contains trillions of microbial cells and has been found to contribute to both local and systemic homeostasis. In both health and disease, a dynamic interrelationship between gut microbiome activity and the host immune system has been identified. Gastrointestinal dysbiosis has been described as having an important role in obesity, diabetes mellitus, liver disease, cardiovascular and neuropsychiatric disorders, neoplasia, as well as autoimmunity. Recent scientific data indicates a notable role of dysbiosis in the pathogenesis of SSc-related digestive involvement together with various other clinical manifestations. The present review aims to summarize the recent findings regarding digestive dysbiosis as well as the relationship between gastrointestinal microbiota and certain features of SSc.

Systemic lupus erythematosus (SLE) is a chronic, multifactorial autoimmune disease with complex pathogenesis characterized by the imbalance of pro-inflammatory and anti-inflammatory cytokines. Janus kinases (JAKs), intracellular non-receptor tyrosine kinases, are essential for signal pathways of many cytokines. The JAK signal transducers and activators of transcription (STAT) pathways consist of four JAK kinases and seven STATs family members. The dysregulation of JAK-STAT pathways represents an important process in the pathogenesis of SLE. Thus, the use of therapies that target specific signaling pathways would be a challenge in SLE. It is well known that JAK inhibitors have real potential for the treatment of rheumatic diseases, but their efficacy in the treatment of SLE remains to be determined. JAK inhibitors are currently being investigated in phase II and III trials and are considered to become the next stage in SLE therapy. In this review, we report the current data regarding the efficacy of JAK inhibitors in SLE. The development of clinically useful kinase inhibitors might improve upon traditional therapeutic strategies.

The 50-year-old patient presented to our clinic for the first time in March 2019, complaining of an altered general condition, inflammatory pain in the small joints of her left hand, right fist and bilateral forefoot, morning stiffness of over 60 minutes, swelling of the right carpal and bilateral metatarsophalangeal joints and finger III left hand dactylitis. The patient is an employee and denies alcohol and tobacco use. From the hereditary antecedents we point a sister diagnosed with psoriasis vulgaris, another sister who died of a gastric neoplasm and her father having cardiovascular diseases.

Interstitial lung disease (ILD) is a severe and frequent manifestation of connective tissue diseases (CTD). Due to its debilitating potential, it requires serious evaluation and treatment. The prevalence of ILD in systemic lupus erythematosus (SLE) is still controversial. Therefore, in order to establish the diagnosis of ILD, an overlap syndrome must be excluded. Increasing the identification of SLE-associated ILD cases should become a target. To treat this complication, various therapies are now being proposed. To date, no placebo-controlled studies were conducted. Regarding another CTD, systemic sclerosis (SSc), SSc-associated ILD is considered one of the leading causes of mortality. The incidence of ILD varies among disease subtypes, being influenced by diagnostic method, but also by disease duration. Due to the high prevalence of this complication, all SSc patients should be investigated for ILD at the time of SSc diagnosis and during the course of the disease. Fortunately, progress was made in terms of treatment. Nintedanib, a tyrosine kinases inhibitor, showed promising results. It appeared to decrease the rate of progression of ILD compared to placebo. This review aimed to provide up-to-date findings related to SLE-associated ILD and SSc-associated ILD, in order to raise awareness of their diagnosis and management.

Hyperlipidemia is a risk factor for cardiovascular disease – the leading cause of death globally. Increased understanding of the cost-effectiveness of hyperlipidemia treatment in low- and middle-income countries can guide approaches to hyperlipidemia management in resource-limited environments. We conducted a systematic review of the evidence on the cost-effectiveness of hyperlipidemia medication treatment in low- and middle-income countries using studies published between January 2010 and April 2020. We abstracted study details, including study design, treatment setting, intervention type, health metrics, costs standardized to constant 2019 US dollars, and cost-effectiveness measures including average and incremental cost-effectiveness ratios. Comparisons across studies suggested that treatment via polypill is generally more cost-effective than statin-only therapy, and that primary prevention is more cost-effective than secondary prevention. Treating hyperlipidemia at a threshold of 5.7 mmol/l comes at a higher cost per disability-adjusted life-years averted than at a threshold of 6.2 mmol/l. Most pharmacological treatment strategies for hyperlipidemia were found to be cost-effective in most of the examined low- and middle-income countries.

Cadmium (Cd) is found at high concentrations in tobacco smoke due to its volatility when tobacco is burned. Inhaled Cd is linked to smoking-related respiratory diseases, such as chronic obstructive pulmonary disease and lung cancer. Alterations in mucociliary clearance, squamous metaplasia, and carcinoma are commonly observed in the respiratory tract of animals exposed to Cd. In vitro cell models widely used to study mechanisms underlying Cd toxicity are not suitable for studying its effects on mucociliary clearance and airway tissue remodeling. Herein we assess Cd-induced functional and structural changes in a well-differentiated human air-liquid-interface (ALI) airway tissue model. Acute treatments with Cd induced aberrant expression and secretion of mucins, impaired cilia functions, and squamous differentiation, and produced persistent oxidative stress and enhanced release of pro-inflammatory cytokines and matrix metalloproteinases. Accumulation of intracellular Cd was associated with sustained oxidative stress and inflammation, which, in turn, may have initiated squamous differentiation in ALI cultures. These observations demonstrate that ALI airway tissue models can recapitulate the functional and structural alterations in Cd-exposed animals, suggesting their potential application for studying tissue responses related to respiratory toxicants like those present in tobacco smoke.

Cardiovascular diseases (CVD) are one of the leading causes of high mortality in patients with systemic lupus erythematosus (SLE). The Framingham risk score and other traditional risk factors do not fully reflect the CVD risk in SLE patients. Therefore, in order to stratify these high-risk patients, additional biomarkers for subclinical CVD are needed. The mechanisms of atherogenesis in SLE are still being investigated. During the past decades, many reports recognized that inflammation plays a crucial role in the development of atherosclerosis. The aim of this report is to present novel proinflammatory and pro-atherosclerotic risk factors that are closely related to SLE inflammation and which determine an increased risk for the occurrence of early cardiovascular events.

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by heterogeneous changes involving numerous organs and systems. The currently available data indicate that muscle injury (both smooth and striated muscles) is widespread and leads to significant morbidity, either directly or indirectly. From the consequences of smooth muscle involvement in the tunica media of blood vessels or at the level of the digestive tract, to skeletal myopathy (which may be interpreted strictly in the context of SSc, or as an overlap with idiopathic inflammatory myopathies), muscular injury in scleroderma translates to a number of notable clinical manifestations. Heart involvement in SSc is heterogenous depending on the definition used in the various studies. The majority of SSc patients experience a silent form of cardiac disease. The present review summarizes certain important features of myocardial, as well as smooth and skeletal muscle involvement in SSc. Further research is needed to fully describe and understand the pathogenic pathways and the implications of muscle involvement in scleroderma.

BACKGROUND: Intake of trans fatty acids (TFAs) increases LDL cholesterol, decreases HDL cholesterol, and increases the risk of heart disease morbidity and mortality. Many food products potentially contain industrially produced or ruminant TFAs. However, little is known about the dietary sources of plasma TFA concentrations. OBJECTIVE: The objective of this study was to examine associations between foods consumed and plasma TFA concentrations using 24-h dietary recall data and plasma TFA measures among adults aged ≥20 y who participated in the NHANES 2009–2010 in the United States. METHODS: Over 4400 food products in the dietary interview data were categorized into 32 food and beverage groups/subgroups. Four major plasma TFAs (palmitelaidic acid, elaidic acid, vaccenic acid, linolelaidic acid) and the sum of the 4 TFAs (sumTFAs) were analyzed using GC-MS. Multivariable linear regression analyses were conducted to identify associations of plasma TFAs with all 32 food and beverage groups/subgroups, controlling for the potential confounding effects of 11 demographic, socioeconomic, behavioral, lifestyle, and health-related variables. RESULTS: Consumption of the following food groups/subgroups was significantly associated with elevated plasma TFA concentrations: cream substitutes (P

Dose-response modeling of in vitro micronucleus test (IVMNT) data was evaluated to determine if the approach has value in discriminating among different tobacco products. Micronucleus responses were generated in L5178Y/Tk+/- mouse lymphoma cells and TK6 human lymphoblastoid cells from a series of whole smoke solutions (WSSs) expected to have different levels of genotoxicity based on differences in their machine-generated smoke constituents. Eight WSSs were prepared by machine smoking different numbers (20 or 60) of two commercial cigarettes (Marlboro Silver or Red) under International Standardization Organization (ISO) or Health Canada Intense (HCI) smoking machine regimens and tested in the two cell lines with and without rat liver S9 activation. The S9-mediated IVMNT dose-response data from the WSSs were evaluated with PROAST software and Benchmark Doses (BMDs) and their upper and lower confidence intervals (CIs) were generated. IVMNT data differed based on the number and type of cigarettes smoked and smoking machine regimen. The IVMNT responses produced in mouse lymphoma cells generally were greater than in TK6 cells, but the ability of the two cell types to differentiate between WSSs was similar. The results indicate that BMD potency ranking was useful for differentiating between IVMNT responses.

Foreign health aid forms a substantial portion of health spending in many low- and middle-income countries (LMICs). It can be either vertical (funds earmarked for specific diseases) or horizontal (funds used for broad health sector strengthening). Historically, most health aid has been disbursed vertically toward key infectious diseases, with minimal allocations to noncommunicable diseases (NCDs). High NCD burden in LMICs underscores a need for increased assistance toward NCD objectives, but evidence on the outcomes of health aid for NCDs is sparse. We obtained annual data on cause-specific deaths and disability-adjusted life years (DALYs) for four leading NCDs across 116 countries, 2000–2016, and evaluated the relationship between these indicators and vertical and horizontal health aid using country fixed-effects models with 1-to-5-year lagged effects. After adjusting for fixed and time-variant country heterogeneity, vertical assistance for NCDs was significantly associated with subsequent reductions in NCD morbidity and mortality, particularly for persons under age 70 and for cardiovascular and chronic respiratory diseases. An additional dollar in per-capita NCD vertical assistance corresponded to reductions in the average annual NCD burden of 7,459 DALYs/281 deaths after one year, 7,728 DALYs/319 deaths after two years, and 8,957 DALYs/346 deaths after three years. The findings suggest that vertical assistance for NCD programs may be an appropriate mechanism for addressing short-term NCD needs in LMICs, where it may help to fill health sector gaps in NCD care, but longer-term evaluation is needed for assessing the role of horizontal assistance.

BackgroundWe revisited the association between progress in MPOWER implementation from 2008 to 2016 and smoking prevalence from 2009 to 2017 and offered an in-depth understanding of differential outcomes for various country groups.MethodsWe used data from six rounds of the WHO Reports on the Global Tobacco Epidemic and calculated a composite MPOWER Score for each country in each period. We categorised the countries in four initial conditions based on their tobacco control preparedness measured by MPOWER score in 2008 and smoking burden measured by age-adjusted adult daily smoking prevalence in 2006: (1) High MPOWER – high prevalence (HM-HP). (2) High MPOWER – low prevalence (HM-LP). (3) Low MPOWER – high prevalence (LM-HP). (4) Low MPOWER – low prevalence (LM-LP). We estimated the association of age-adjusted adult daily smoking prevalence with MPOWER Score and cigarette tax rates using two-way fixed-effects panel regression models including both year and country fixed effects.ResultsA unit increase of the MPOWER Score was associated with 0.39 and 0.50 percentage points decrease in adult daily smoking prevalence for HM-HP and HM-LP countries, respectively. When tax rate was controlled for separately from MPOWE, an increase in tax rate showed a negative association with daily smoking prevalence for HM-HP and LM-LP countries, while the MPOWE Score showed a negative association for all initial condition country groups except for LM-LP countries.ConclusionA decade after the introduction of the WHO MPOWER package, we observed that the countries with higher initial tobacco control preparedness and higher smoking burden were able to reduce the adult daily smoking prevalence significantly.

Cardiorenal syndrome encompasses complex multifactorial facets and carries significant morbidity and mortality worldwide. The bi-directional relationship between the heart and kidneys, where dysfunction in one organ worsens the function of the other, has been the leading motor for research in the last few years. In the pathophysiological process, small noncoding RNAs, epigenetics, vascular growth factors, oxidative stress, hemodynamic factors, and biomarkers play a pivotal role in the development of cardiorenal syndrome. It is therefore important to elucidate all the mechanisms in order to provide diagnostic and treatments tools. This review summarizes the hemodynamic and non-hemodynamic pathways along with biomarkers that could be the next target for diagnosis, treatment, and prognosis in cardiorenal syndrome.

Objectives Intake of trans fatty acids (TFA) increases the risk of cardiovascular disease. Assessment of TFA exposure in the population is key for determining TFA burden and monitoring change over time. One approach for TFA monitoring is measurement of TFA levels in plasma. Understanding costs associated with this approach can facilitate program planning, implementation and scale-up. This report provides an assessment of costs associated with a pilot program to measure plasma TFA levels in Thailand. Study design Cost analysis in a laboratory facility in Thailand. Methods We defined three broad cost modules: laboratory, personnel, and facility costs, which were further classified into sub-components and into fixed and variable categories. Costs were estimated based on the number of processed plasma samples (100–2700 in increments of 50) per year over a certain number of years (1–5), in both USD and Thai Baht. Total cost and average costs per sample were estimated across a range of samples processed. Results The average cost per sample of analyzing 900 samples annually over 5 years was estimated at USD186. Laboratory, personnel, and facility costs constitute 67%, 23%, and 10% of costs, respectively. The breakdown across fixed costs, such as laboratory instruments and personnel, and variable costs, such as chemical supplies, was 60% and 40%, respectively. Average costs decline as more samples are processed: the cost per sample for analyzing 100, 500, 1500, and 2500 samples per year over 5 years is USD1351, USD301, USD195; and USD177, respectively. Conclusions Laboratory analysis of plasma TFA levels has high potential for economies of scale, encouraging a long-term approach to TFA monitoring initiatives, particularly in countries that already maintain national biometric repositories.

Objective Our objective was to improve understanding of the differences in use behavior and exposure when smoking menthol and non-menthol cigarettes using a 2-part cross-over design. Methods Adult daily smokers were assigned randomly to alternate between 2 weeks of exclusively smoking a menthol test cigarette or a non-menthol test cigarette. Urine and saliva were collected for biomarker measurements; carbon monoxide (CO) was measured, and participants smoked test cigarettes through a CreSS® smoking topography device during 3 clinic visits. Participants turned in their cigarette butts from the test periods for determination of mouth level nicotine and completed subjective questionnaires related to the test cigarettes. Results Regardless of cigarette preference, participants had higher salivary cotinine when smoking the non-menthol test cigarette, but there were no significant differences detected in urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol between the 2 test cigarettes. Mouth level nicotine, puff volume, and puff duration were significantly higher when smoking the menthol brand. Both menthol and non-menthol smokers reported significantly lower enjoyment and satisfaction scores for test cigarettes compared with their brand of choice. Conclusions Our results suggest that mentholation has an effect on measures of smoking behavior and that mouth level nicotine is a useful indicator of between-brand smoke exposure.

Background Intake of trans fatty acids (TFAs) increases LDL cholesterol, decreases HDL cholesterol, and increases the risk of heart disease morbidity and mortality. Many food products potentially contain industrially produced or ruminant TFAs. However, little is known about the dietary sources of plasma TFA concentrations. Objective The objective of this study was to examine associations between foods consumed and plasma TFA concentrations using 24-h dietary recall data and plasma TFA measures among adults aged ≥20 y who participated in the NHANES 2009-2010 in the United States. Methods Over 4400 food products in the dietary interview data were categorized into 32 food and beverage groups/subgroups. Four major plasma TFAs (palmitelaidic acid, elaidic acid, vaccenic acid, linolelaidic acid) and the sum of the 4 TFAs (sumTFAs) were analyzed using GC-MS. Multivariable linear regression analyses were conducted to identify associations of plasma TFAs with all 32 food and beverage groups/subgroups, controlling for the potential confounding effects of 11 demographic, socioeconomic, behavioral, lifestyle, and health-related variables. Results Consumption of the following food groups/subgroups was significantly associated with elevated plasma TFA concentrations: cream substitutes (P

OBJECTIVE Our objective was to characterize mainstream smoke constituent deliveries from SPECTRUM variable nicotine research cigarettes under 2 machine smoking regimens. SPECTRUM cigarettes are manufactured by the 22nd Century company for the National Institute on Drug Abuse, National Institutes of Health to contain varying (including reduced) levels of nicotine. METHODS Mainstream smoke constituent deliveries of "tar," nicotine, carbon monoxide, tobacco-specific nitrosamines (N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)), benzo[a]pyrene, aromatic amines, and carbonyls were analyzed in 23 varieties of SPECTRUM cigarettes using ISO 17025 accredited methods. RESULTS Data are presented as means and standard deviations of 5 replicates for all analytes. CONCLUSIONS Under the ISO smoking regimen, mean levels of many smoke emissions for SPECTRUM varieties were comparable to the 3R4F research cigarette. Calculated SPECTRUM elasticity ranged from 1.6 to 4.0. Accordingly, under intense machine smoking conditions differences in emissions of SPECTRUM cigarettes were apparent. In addition, NNN increased with smoke nicotine while the same rate of change was not seen for NNK. It is important to monitor levels of chemicals of public health concern and regulatory interest as technologies emerge to reduce levels of nicotine or other targeted chemicals in tobacco products.

Background: The workplace is one of the major locations outside of the home for nonsmokers’ exposure to secondhand smoke (SHS). New policies in many U.S. states and localities restrict or prohibit smoking in the workplace, and information on current trends in the exposure of nonsmokers to SHS across various occupational groups is therefore needed. Objective: We evaluated temporal trends in SHS exposure among nonsmoking workers in the United States and identified those occupations with workers with the highest levels of SHS exposure. Methods: We combined serum cotinine (sCOT) measurements and questionnaire data from five survey cycles of the National Health and Nutrition Examination Survey (NHANES: 2001–2010). Trends in SHS exposure by occupations were determined from percent changes and least-squares geometric means (LSGMs) of sCOT concentrations computed using sample-weighted multiple regression models. Results: Between NHANES 2001–2002 and NHANES 2009–2010, LSGMs of sCOT levels had changed –25% (95% CI: –39, –7%) in nonsmoking workers. The largest decrease was identified among food preparation workers [–54% (95% CI: –74, –19%)], followed by white-collar [–40%, (95% CI: –56, –19%)] and blue-collar workers (–32%, 95% CI: –51, –5%). LSGMs of sCOT remained highest in food preparation workers in all survey cycles, but the gap between occupations narrowed in the latest survey cycle (2009–2010). For example, the gap in LSGMs of sCOT between food preparation and science/education workers dropped > 70% during 2000 to 2010. Conclusions: During the period from 2001 to 2010, the overall SHS exposure in nonsmoking workers declined with substantial drops in food preparation/service and blue-collar workers. Although disparities persist in SHS exposure, the gaps among occupations have narrowed. Citation: Wei B, Bernert JT, Blount BC, Sosnoff CS, Wang L, Richter P, Pirkle JL. 2016. Temporal trends of secondhand smoke exposure: nonsmoking workers in the United States (NHANES 2001–2010). Environ Health Perspect 124:1568–1574; http://dx.doi.org/10.1289/EHP165

Many cigarette smoke-associated airway diseases involve alterations in mucin homeostasis. With the rationale that relevant tissue responses can be measured to evaluate the adverse health effects of tobacco products, we assessed changes in mucin secretion and the density and size of goblet cells in an in vitro human air-liquid-interface (ALI) airway tissue model after exposure to a tobacco smoke solution. Cultures were exposed daily for up to five consecutive days to a whole smoke solution (WSS) prepared by machine smoking Marlboro Red or Marlboro Silver cigarettes using the Canadian Intense (CI) protocol. Both WSSs induced concentration- and time-related hypersecretion of mucins 5AC and 5B, accompanied by up-regulation of the respective mucin genes. Mucin secretion returned to baseline levels following a 14-day recovery period. Mucin-secreting goblet cells exhibited increased cell density and decreased size after 5 daily treatments then recovered to their normal size, but with decreased cell density, 14 days after the last treatment. The beating frequency of ciliated cells, which plays a key role in mucociliary clearance, was increased by 5 daily treatments with the CI WSSs then reverted to baseline levels following a 7-day recovery. Taken together, our results indicate that ALI cultures can be used to measure the modulation of mucin production, secretion, and clearance, disturbances that are manifested in tobacco smoke-related diseases, such as chronic obstructive pulmonary disease. Measuring tissue responses directly relevant to the respiratory toxicity of cigarette smoke may provide useful information in support of science-based regulatory decisions.

Despite a remarkable downward trend since 2000, child labour remains a reality for 168 million children worldwide (from 245 million in 2000). Of those children, more than half are engaged in hazardous work that directly endangers their health, safety, and moral development. These latest statistics from the International Labour Organization illustrate a pressing concern for today’s world and call for integrated efforts to tackle them. This article proposes a framework for development practitioners and policymakers to help them design interventions with a particular focus on financial service providers. We briefly describe root causes of child labour – including demand, social norms, access, costs and quality of education, vulnerability and risk exposure, and income poverty – and then propose innovative interventions that financial service providers can engage in to address, where possible, each of the causes. The article then presents evidence from recent experimental research in Pakistan which shows the significant positive effect that an innovative health and accidental death insurance product had on reducing child labour. Further evidence from experimental research with an associated school fees loan and an awareness campaign in Nigeria, and an integrated training package and sensitization programme in Mali, illustrate that the impact of interventions on child labour, education, and poverty are not always straightforward.

Quantifying health-related biological effects, like genotoxicity, could provide a way of distinguishing between tobacco products. In order to develop tools for using genotoxicty data to quantitatively evaluate the risk of tobacco products, we tested five carcinogens found in cigarette smoke, 4-aminobiphenyl (4- ABP), benzo[a]pyrene (BaP), cadmium (in the form of CdCl(2)), 2-amino-3,4-dimethyl-3H-imidazo[4,5-f] quinoline (MelQ) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), in the mouse lymphoma assay (MLA). The resulting mutagenicity dose responses were analyzed by various quantitative approaches and their strengths and weaknesses for distinguishing responses in the MLA were evaluated. L5178Y/Tk(+/−) 3.7.2C mouse lymphoma cells were treated with four to seven concentrations of each chemical for 4 h. Only CdCl(2) produced a positive response without metabolic activation (S9); all five chemicals produced dose-dependent increases in cytotoxicity and mutagenicity with S9. The lowest dose exceeding the global evaluation factor, the benchmark dose producing a 10%, 50%, 100% or 200% increase in the background frequency (BMD(10), BMD(50), BMD(100) and BMD(200)), the no observed genotoxic effect level (NOGEL), the lowest observed genotoxic effect level (LOGEL) and the mutagenic potency expressed as a mutant frequency per micromole of chemical, were calculated for all the positive responses. All the quantitative metrics had similar rank orders for the agents’ ability to induce mutation, from the most to least potent as CdCl(2)(-S9) > BaP(+S9) > CdCl(2)(+S9) > MeIQ(+S9) > 4-ABP(+S9) > NNK(+S9). However, the metric values for the different chemical responses (i.e. the ratio of the greatest value to the least value) for the different chemicals ranged from 16-fold (BMD(10)) to 572-fold (mutagenic potency). These results suggest that data from the MLA are capable of discriminating the mutagenicity of various constituents of cigarette smoke, and that quantitative analyses are available that can be useful in distinguishing between the exposure responses.

In 2007 the International Labour Organization (ILO) launched the “Microfinance for Decent Work” (MF4DW) action research programme, which was intended to foster the development of innovative financial and non-financial products and services for microfinance clients. A bottom-up approach was pursued where microfinance institutions could propose innovations that promised to have a social impact. The piloting of these interventions was complemented by an impact evaluation. In this article the 17 selected innovations are described as well as the accompanying impact evaluation approaches. Even if final evaluation results are not available yet, lessons learnt during the implementation of the MF4DW initiative seem worthwhile to be made available to other programmes targeting a systematic improvement of microfinance impact.

Cytotoxic properties of tobacco smoke are associated with chronic tobacco-related diseases. The cytotoxicity of tobacco smoke can be tested with short-term predictive assays. In this study, we compare eight mainstream cigarette smoke condensates (CSCs) from commercial and experimental cigarettes in three different cytotoxicity assays with unique and overlapping endpoints. The CSCs demonstrated cytotoxicity in all assays. In the multiple cytotoxicity endpoint (MCE) assay with TK-6 cells, the cigarette varieties that had the highest EC50s for reduced cell growth also showed a positive dose-response relationship for necrotic cells. In the IdMOC multiple cell-type co-culture (MCTCC) system, all CSCs reduced the viability of the cells. Low concentrations of some CSCs had a stimulatory effect in lung microvascular endothelial cells and small airway epithelial cells. In the neutral dye assay (NDA), except for a 100% flue-cured tobacco CSC, there was little consistency between CSCs producing morphological evidence of moderate or greater toxicity and the CSCs with the lowest EC50s in the MCE or MCTCC assays. Overall, cigarettes made with flue-cured tobacco were the most cytotoxic across the assays. When results were expressed on a per-mg of nicotine basis, lower tar cigarettes were the most cytotoxic in primary human respiratory cells.

Cigarette smoke condensate (CSC) is genotoxic in nearly all assays in which it has been tested. In this study, we investigated the mutagenicity of 11 CSCs using the microwell and soft-agar versions of the mouse lymphoma assay (MLA). These CSCs were prepared from commercial or experimental cigarettes, 10 of them were produced using International Organisation for Standardisation (ISO) conditions and one CSC was generated using intense Massachusetts Department of Public Health (MDPH) conditions. In the presence of rat liver S9, the L5178Y/Tk(+/-) mouse lymphoma cells were treated with 11 CSCs at different concentrations (25-200 μg/ml) for 4 h. All CSCs resulted in dose-dependent increases of both cytotoxicity and mutagenicity in both versions of the MLA. The mutagenic potencies of the CSCs were calculated as mutant frequency per microgram CSC from the slope of the linear regression of the dose-response curves and showed no correlations with the tar yield of the cigarette or nicotine concentrations of the CSCs. Comparing two CSCs produced from the same commercial cigarettes using two different smoking conditions, the one generated under ISO conditions was more mutagenic than the other generated under intense conditions on a per microgram CSC basis. We also examined the loss of heterozygosity (LOH) at four microsatellite loci spanning the entire chromosome 11 for the mutants induced by 11 CSCs. The most common type of mutation observed was LOH with chromosome damage spanning less than ∼34 Mbp. These results indicate that the MLA identifies different genotoxic potencies among a variety of CSCs and that the results from both versions of the assay are comparable.

OBJECTIVE: This study examines child poisonings resulting from ingestion of tobacco products throughout the nation and assesses the potential toxicity of novel smokeless tobacco products, which are of concern with their discreet form, candy-like appearance, and added flavorings that may be attractive to young children. METHODS: Data representing all single-substance, accidental poisonings resulting from ingestion of tobacco products by children RESULTS: A total of 13705 tobacco product ingestion cases were reported, >70% of which involved infants CONCLUSION: In light of the novelty and potential harm of dissolvable nicotine products, public health authorities are advised to study these products to determine the appropriate regulatory approach.

Cigarettes vary in tobacco blend, filter ventilation, additives, and other physical and chemical properties, but little is known regarding potential differences in toxicity to a smoker's airway epithelia. We compared changes in gene expression and cytokine production in primary normal human bronchial epithelial cells following treatment for 18 h with cigarette smoke condensates (CSCs) prepared from five commercial and four research cigarettes, at doses of approximately 4 microg/ml nicotine. Nine of the CSCs were produced under a standard International Organization for Standardization smoking machine regimen and one was produced by a more intense smoking machine regimen. Isolated messenger RNA (mRNA) was analyzed by microarray hybridization, and media was analyzed for secreted cytokines and chemokines. Twenty-one genes were differentially expressed by at least 9 of the 10 CSCs by more than twofold, including genes encoding detoxifying and antioxidant proteins. Cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) and NAD(P)H dehydrogenase, quinone 1 (NQO-1) were selected for validation with quantitative real-time PCR (qRT-PCR) and Western blot analyses. NQO-1 expression determined with microarrays, qRT-PCR, and Western blotting differed among the CSC types, with good correlation among the different assays. CYP1A1 mRNA levels varied substantially, but there was little correlation with the protein levels. For each CSC, the three most induced and three most repressed genes were identified. These genes may be useful as markers of exposure to that particular cigarette type. Furthermore, differences in interleukin-8 secretion were observed. These studies lay the foundation for future investigations to analyze differences in the responses of in vivo systems to tobacco products marketed with claims of reduced exposure or reduced harm.

In 2002, the First Conference on Menthol Cigarettes brought together researchers from diverse backgrounds to summarize what is known about menthol cigarettes and the people who smoke them, and to identify areas of needed research on menthol cigarettes. Since the conference, PubMed reports 24 articles, including the conference proceedings, on menthol cigarettes and African Americans. Many of the articles address epidemiological or biomedical topics. While there has been some focus on social influences and marketing issues, more research and a greater focus on this topic are needed.To stimulate research on a population disproportionately burdened by the health effects of smoking, we conducted small-group discussions in 2005 with adult African American smokers in Atlanta, Georgia. Each group discussion focused on a different topic: smoking behavior and preferences, perceptions of social influences, health effects and perceived harmfulness of menthol, quitting menthol cigarette smoking, or the influence of marketing and advertising of menthol cigarettes.Themes emerged from the discussions: (1) emulation of black culture by white youth and racial integration of neighborhoods and communities may have modified the perception that African Americans smoke menthol cigarettes and whites smoke non-menthol cigarettes; (2) non-menthol cigarette smokers were thought to be 'hardcore' smokers with less interest in quitting; (3) switching to non-menthol cigarettes was discussed as a way of quitting cigarettes for habitual menthol smokers; and, (4) smoking menthol cigarettes was thought to lead to fewer negative health effects.Some topics suggested by the participants warrant further investigation. More research is needed to assess the pervasiveness of these beliefs and their potential utility for smoking cessation interventions.

We developed and implemented a national surveillance system to monitor and reduce the levels of toxic chemicals in tobacco smoke. A developmental Healthy People 2010 (HP 2010) objective was revised to report on levels of three categories of chemicals—tobacco-specific nitrosamines, polyaromatic hydrocarbons, and volatile organic compounds—in the smoke of leading U.S. cigarette brands. Unit-based sales-weighted average levels were calculated for each chemical category. The target for the new HP 2010 objective is a 10% reduction in unit-based sales-weighted average levels of each chemical category. The Centers for Disease Control and Prevention provided the baseline, target data, and laboratory analyses. A national data source, national baseline data, and target were presented to the Healthy People Steering Committee during 2005 Midcourse Review. Approval of the revised objective initiated the surveillance of three major classes of toxic chemicals in cigarette smoke. The approved objective provides a feasible, innovative approach for monitoring and supporting measurable population-based reductions in levels of toxic and carcinogenic chemicals in tobacco smoke.

To provide researchers an extensive characterization of the SPECTRUM variable nicotine research cigarettes.Data on cigarette physical properties, nicotine content, harmful and potentially harmful constituents in the tobacco filler was compiled.Data on physical properties, concentrations of menthol, nicotine and minor alkaloids, tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons, ammonia, and toxic metals in the filler tobacco for all available varieties of Spectrum research cigarettes are provided. The similarity in the chemistry and physical properties of SPECTRUM cigarettes to commercial cigarettes renders them acceptable for use in behavioral studies. Baseline information on harmful and potentially harmful constituents in research tobacco products, particularly constituent levels such as minor alkaloids that fall outside typical ranges reported for commercial, provide researchers with the opportunity to monitor smoking behavior and to identify biomarkers that will inform efforts to understand the role of nicotine in creating and sustaining addiction.Well characterized research cigarettes suitable for human consumption are an important tool in clinical studies for investigating the physiological impacts of cigarettes delivering various levels of nicotine, the impact of reduced nicotine cigarettes on nicotine addiction, and the relationship between nicotine dose and smoking behavior.

Background: Although several epidemiological studies have examined the mortality among users of spit tobacco, none have compared mortality of former cigarette smokers who substitute spit tobacco for cigarette smoking (“switchers”) and smokers who quit using tobacco entirely. Methods: A cohort of 116 395 men were identified as switchers (n = 4443) or cigarette smokers who quit using tobacco entirely (n = 111 952) when enrolled in the ongoing US American Cancer Society Cancer Prevention Study II. From 1982 to 31 December 2002, 44 374 of these men died. The mortality hazard ratios (HR) of tobacco-related diseases, including lung cancer, coronary heart disease, stroke and chronic obstructive pulmonary disease, were estimated using Cox proportional hazards regression modelling adjusted for age and other demographic variables, as well as variables associated with smoking history, including number of years smoked, number of cigarettes smoked and age at quitting. Results: After 20 years of follow-up, switchers had a higher rate of death from any cause (HR 1.08, 95% confidence interval (CI) 1.01 to 1.15), lung cancer (HR 1.46, 95% CI 1.24 to 1.73), coronary heart disease (HR 1.13, 95% CI 1.00 to 1.29) and stroke (HR 1.24, 95% CI 1.01 to 1.53) than those who quit using tobacco entirely. Conclusion: The risks of dying from major tobacco-related diseases were higher among former cigarette smokers who switched to spit tobacco after they stopped smoking than among those who quit using tobacco entirely.

Rape, a diverse group of smokeless tobacco products indigenous to South America, is generally used as a nasal snuff and contains substantial amount of plant material with or without tobacco. Previously uncharacterized, rape contains addictive and harmful chemicals that may have public health implications for users. Here we report % moisture, pH, and the levels of total nicotine, un-ionized nicotine, flavor-related compounds, tobacco-specific N-nitrosamines (TSNAs) and polycyclic aromatic hydrocarbons (PAHs) for manufactured and hand-made rape. Most rape products were mildly acidic (pH 5.17–6.23) with total nicotine ranging from 6.32 to 47.6 milligram per gram of sample (mg/g). Calculated un-ionized nicotine ranged from 0.03 to 18.5 mg/g with the highest values associated with hand-made rapes (pH 9.75–10.2), which contain alkaline ashes. In tobacco-containing rapes, minor alkaloid levels and Fourier transform infrared spectra were used to confirm the presence of Nicotiana rustica , a high nicotine tobacco species. There was a wide concentration range of TSNAs and PAHs among the rapes analyzed. Several TSNAs and PAHs identified in the products are known or probable carcinogens according to the International Agency for Research on Cancer. Milligram quantities of some non-tobacco constituents, such as camphor, coumarin, and eugenol, warrant additional evaluation.

Diseases and death caused by exposure to tobacco smoke have become the single most serious preventable public health concern. Thus, biomarkers that can monitor tobacco exposure and health effects can play a critical role in tobacco product regulation and public health policy. Biomarkers of exposure to tobacco toxicants are well established and have been used in population studies to establish public policy regarding exposure to second-hand smoke, an example being the nicotine metabolite cotinine, which can be measured in urine. Biomarkers of biological response to tobacco smoking range from those indicative of inflammation to mRNA and microRNA patterns related to tobacco use and/or disease state. Biomarkers identifying individuals with an increased risk for a pathological response to tobacco have also been described. The challenge for any novel technology or biomarker is its translation to clinical and/or regulatory application, a process that requires first technical validation of the assay and then careful consideration of the context the biomarker assay may be used in the regulatory setting. Nonetheless, the current efforts to investigate new biomarker of tobacco smoke exposure promise to offer powerful new tools in addressing the health hazards of tobacco product use. This review will examine such biomarkers, albeit with a focus on those related to cigarette smoking.

Objective: Survey of nicotine, tar, and carbon monoxide (CO) smoke deliveries from 77 cigarette brands purchased in 35 countries was conducted using a standardised machine smoking method. The goal of this study was to determine regional variations and differences in the tar, nicotine, and CO smoke yields of a cigarette brand manufactured by a leading transnational corporation and of non-US locally popular cigarette brands. Design: The majority of the cigarettes were purchased in each of the participating countries by delegate members of the World Health Organization and forwarded to the Centers for Disease Control and Prevention for analysis. Smoke deliveries were determined using a standardised smoking machine method and subsequent gravimetric and gas chromatography analysis. Results: The smoke deliveries varied widely. Mainstream smoke deliveries varied from 6.8 to 21.6 mg tar/cigarette, 0.5 to 1.6 mg nicotine/cigarette, and 5.9 to 17.4 mg CO/cigarette. In addition to the smoke deliveries, the cigarettes were examined to determine physical parameters such as filter composition, length, and ventilation levels. Conclusion: Analysis of the smoke deliveries suggested that cigarettes from the Eastern Mediterranean, Southeast Asia, and Western Pacific WHO regions tended to have higher tar, nicotine, and CO smoke deliveries than did brands from the European, American, or African WHO regions surveyed.

Approximately one-fourth of all cigarettes sold in the United States are mentholated. An understanding of the consequences, patterns, and correlates of menthol cigarette use can guide the development and implementation of strategies to reduce smoking prevalence and smoking-attributable morbidity and mortality. This paper summarizes the literature on the health effects of mentholated cigarettes and describes various patterns of use as indicated by consumption and survey data from the United States and other nations. The epidemiological literature on menthol cigarettes and cancer risk is inconclusive regarding whether these cigarettes confer a risk for cancer above that of nonmentholated varieties. Available data indicate that mentholated cigarettes are at least as dangerous as their nonmentholated counterparts. In addition, because mentholation improves the taste of cigarettes for a substantial segment of the smoking population and appears to mask disease symptoms, this additive may facilitate initiation or inhibit quitting. Menthol market share is high in the Philippines (60%), Cameroon (35%-40%), Hong Kong (26%), the United States (26%), and Singapore (22%). Newport has become the leading menthol brand in the United States. Surveys from four nations indicate that menthol use among adult smokers is more common among females than males. Among U.S. smokers, 68.9% of Blacks, 29.2% of Hispanics, and 22.4% of Whites reported smoking a mentholated variety. Research is needed to better explain factors that may influence menthol preference, such as marketing, risk perceptions, brand formulation, and taste preferences. Such research would guide the development of potentially more effective programs and policies.

Background The cadmium (Cd) present in air pollutants and cigarette smoke has the potential of causing multiple adverse health outcomes involving damage to pulmonary and cardiovascular tissue. Injury to pulmonary epithelium may include alterations in tight junction (TJ) integrity, resulting in impaired epithelial barrier function and enhanced penetration of chemicals and biomolecules. Herein, we investigated mechanisms involved in the disruption of TJ integrity by Cd exposure using an in vitro human air-liquid-interface (ALI) airway tissue model derived from normal primary human bronchial epithelial cells. Methods ALI cultures were exposed to noncytotoxic doses of CdCl2 basolaterally and TJ integrity was measured by Trans-Epithelial Electrical Resistance (TEER) and immunofluorescence staining with TJ markers. PCR array analysis was used to identify genes involved with TJ collapse. To explore the involvement of kinase signaling pathways, cultures were treated with CdCl2 in the presence of kinase inhibitors specific for cellular Src or Protein Kinase C (PKC). Results Noncytotoxic doses of CdCl2 resulted in the collapse of barrier function, as demonstrated by TEER measurements and Zonula occludens-1 (ZO-1) and occludin staining. CdCl2 exposure altered the expression of several groups of genes encoding proteins involved in TJ homeostasis. In particular, down-regulation of select junction-interacting proteins suggested that a possible mechanism for Cd toxicity involves disruption of the peripheral junctional complexes implicated in connecting membrane-bound TJ components to the actin cytoskeleton. Inhibition of kinase signaling using inhibitors specific for cellular Src or PKC preserved the integrity of TJs, possibly by preventing occludin tyrosine hyperphosphorylation, rather than reversing the down-regulation of the junction-interacting proteins. Conclusions Our findings indicate that acute doses of Cd likely disrupt TJ integrity in human ALI airway cultures both through occludin hyperphosphorylation via kinase activation and by direct disruption of the junction-interacting complex.

Diseases and death caused by exposure to tobacco smoke have become the single most serious preventable public health concern. Thus, biomarkers that can monitor tobacco exposure and health effects can play a critical role in tobacco product regulation and public health policy. Biomarkers of exposure to tobacco toxicants are well established and have been used in population studies to establish public policy regarding exposure to second-hand smoke, an example being the nicotine metabolite cotinine, which can be measured in urine. Biomarkers of biological response to tobacco smoking range from those indicative of inflammation to mRNA and microRNA patterns related to tobacco use and/or disease state. Biomarkers identifying individuals with an increased risk for a pathological response to tobacco have also been described. The challenge for any novel technology or biomarker is its translation to clinical and/or regulatory application, a process that requires first technical validation of the assay and then careful consideration of the context the biomarker assay may be used in the regulatory setting. Nonetheless, the current efforts to investigate new biomarker of tobacco smoke exposure promise to offer powerful new tools in addressing the health hazards of tobacco product use. This review will examine such biomarkers, albeit with a focus on those related to cigarette smoking.

Introduction Tobacco smoke is a source of exposure to thousands of toxic chemicals including lead, a chemical of longstanding public health concern. We assessed trends in blood lead levels in youths and adults with cotinine-verified tobacco smoke exposure by using 10 years of data from the National Health and Nutrition Examination Survey. Methods Geometric mean levels of blood lead are presented for increasing levels of tobacco smoke exposure. Regression models for lead included age, race/ethnicity, poverty, survey year, sex, age of home, birth country, and, for adults, alcohol consumption. Lead levels were evaluated for smokers and nonsmokers on the basis of age of residence and occupation. Results Positive trend tests indicate that a linear relationship exists between smoke exposure and blood lead levels in youths and adults and that secondhand smoke exposure contributes to blood lead levels above the level caused by smoking. Conclusion Youths with secondhand smoke exposure had blood lead levels suggestive of the potential for adverse cognitive outcomes. Despite remediation efforts in housing and the environment and declining smoking rates and secondhand smoke exposure in the United States, tobacco smoke continues to be a substantial source of exposure to lead in vulnerable populations and the population in general.