Impact of Glycosylation on the Local Backbone Flexibility of Well-Defined IgG1-Fc Glycoforms Using Hydrogen Exchange-Mass Spectrometry

We have used hydrogen exchange–mass spectrometry to characterize local backbone flexibility of 4 well-defined IgG1-Fc glycoforms expressed and purified from Pichia pastoris, 2 of which were prepared using subsequent in vitro enzymatic treatments. Progressively decreasing the size of the N-linked N297 oligosaccharide from high mannose (Man8-Man12), to Man5, to GlcNAc, to nonglycosylated N297Q resulted in progressive increases in backbone flexibility. Comparison of these results with recently published physicochemical stability and Fcγ receptor binding data with the same set of glycoproteins provide improved insights into correlations between glycan structure and these pharmaceutical properties. Flexibility significantly increased upon glycan truncation in 2 potential aggregation-prone regions. In addition, a correlation was established between increased local backbone flexibility and increased deamidation at asparagine 315. Interestingly, the opposite trend was observed for oxidation of tryptophan 277 where faster oxidation correlated with decreased local backbone flexibility. Finally, a trend of increasing C'E glycopeptide loop flexibility with decreasing glycan size was observed that correlates with their FcγRIIIa receptor binding properties. These well-defined IgG1-Fc glycoforms serve as a useful model system to identify physicochemical stability and local backbone flexibility data sets potentially discriminating between various IgG glycoforms for potential applicability to future comparability or biosimilarity assessments.     

Effect of correcting for gestational age at birth on population prevalence of early childhood undernutrition

Background

Postmenstrual and/or gestational age-corrected age (CA) is required to apply child growth standards to children born preterm (< 37 weeks gestational age). Yet, CA is rarely used in epidemiologic studies in low- and middle-income countries (LMICs), which may bias population estimates of childhood undernutrition. To evaluate the effect of accounting for GA in the application of growth standards, we used GA-specific standards at birth (INTERGROWTH-21st newborn size standards) in conjunction with CA for preterm-born children in the application of World Health Organization Child Growth Standards postnatally (referred to as ‘CA’ strategy) versus postnatal age for all children, to estimate mean length-for-age (LAZ) and weight-for-age (WAZ) z scores at 0, 3, 12, 24, and 48-months of age in the 2004 Pelotas (Brazil) Birth Cohort.

Results

At birth (n = 4066), mean LAZ was higher and the prevalence of stunting (LAZ < ?2) was lower using CA versus postnatal age (mean ± SD): ? 0.36 ± 1.19 versus ? 0.67 ± 1.32; and 8.3 versus 11.6%, respectively. Odds ratio (OR) and population attributable risk (PAR) of stunting due to preterm birth were attenuated and changed inferences using CA versus postnatal age at birth [OR, 95% confidence interval (CI): 1.32 (95% CI 0.95, 1.82) vs 14.7 (95% CI 11.7, 18.4); PAR 3.1 vs 42.9%]; differences in inferences persisted at 3-months. At 12, 24, and 48-months, preterm birth was associated with stunting, but ORs/PARs remained attenuated using CA compared to postnatal age. Findings were similar for weight-for-age z scores.

Conclusions

Population-based epidemiologic studies in LMICs in which GA is unused or unavailable may overestimate the prevalence of early childhood undernutrition and inflate the fraction of undernutrition attributable to preterm birth.

     

Evaluation and learning in complex,rapidly changing health systems: China’s management of health sector reform

Healthcare systems are increasingly recognised as complex, in which a range of non-linear and emergent behaviours occur. China’s healthcare system is no exception. The hugeness of China, and the variation in conditions in different jurisdictions present very substantial challenges to reformers, and militate against adopting one-size-fits-all policy solutions. As a consequence, approaches to change management in China have frequently emphasised the importance of sub-national experimentation, innovation, and learning. Multiple mechanisms exist within the government structure to allow and encourage flexible implementation of policies, and tailoring of reforms to context. These limit the risk of large-scale policy failures and play a role in exploring new reform directions and potentially systemically-useful practices. They have helped in managing the huge transition that China has undergone from the 1970s onwards. China has historically made use of a number of mechanisms to encourage learning from innovative and emergent policy practices. Policy evaluation is increasingly becoming a tool used to probe emergent practices and inform iterative policy making/refining. This paper examines the case of a central policy research institute whose mandate includes evaluating reforms and providing feedback to the health ministry. Evaluation approaches being used are evolving as Chinese research agencies become increasingly professionalised, and in response to the increasing complexity of reforms. The paper argues that learning from widespread innovation and experimentation is challenging, but necessary for stewardship of large, and rapidly-changing systems.     

Health service utilization,unmet healthcare needs,and the potential of telemedicine services among Korean expatriates

Background

With the significant growth of migration and expatriation, facilitated by increased global mobility, the number of Koreans living abroad as of 2016 is approximately 7.4 million (15% of the Korean population). Healthcare utilization or health problems, especially among expatriates in developing countries, have not been well researched despite the various health risks these individuals are exposed to. Consequently, we identified the health utilization patterns and healthcare needs among Korean expatriates in Vietnam, Cambodia, and Uzbekistan.

Methods

This cross-sectional survey examined 429 Korean expatriates living in Vietnam (n?=?208), Cambodia (n?=?60), and Uzbekistan (n?=?161) who had access to the Internet and were living abroad for at least 6?months. A 67-item questionnaire was used, and feedback was received via an online survey program. Stepwise logistic regression analyses were performed to evaluate factors associated with unmet healthcare needs and preferences of certain type of telemedicine.

Results

We found that 45.5% (195/429) of respondents had used medical services in their country of stay. Among those who visited health institutions >?3 times, the most popular choice was general hospitals (39.4%, 15/38); however, they initially visited Korean doctors’ or local doctors’ offices. The most essential criteria for healthcare service facilities was a “skilled professional” (39.3%, 169/429), 42% wanted a health program for chronic disease management, and 30% wanted specialized internal medicine. A substantial number wanted to access telemedicine services and were willing to pay for this service. They were particularly interested in experts’ second opinion (61.5%, 264/429) and quick, 24-h medical consultations (60.8%, 261/429). Having unmet healthcare needs and being younger was strongly associated with all types of telemedicine networks.

Conclusions

Nearly half of the expatriates in developing countries had unmet healthcare needs. Telemedicine is one potential solution to meet these needs, especially in developing countries.

     

Ukrainian health care system and its chances for successful transition from Soviet legacies

Background

Ukraine, one of the largest states formed on the rubble of the Soviet Union, is widely perceived as a country that has lost its opportunities. Being devastated by corruption, it shows incapable to modernize and enter the economic path of sustainable growth. Similarly in the health care system no deeper reform efforts have been taken in the entire post-soviet period, leaving the system in bonds of ineffective solutions taken out of the Soviet era.

Main body

The recent geopolitical and economic crisis seem to favor the introduction of radical solutions that might lead to a rapid change in the organizational paradigm of the economic system, as well as in health care in Ukraine. In this paper we aim to highlight the key features of the ongoing health reform in Ukraine, identify basic challenges for it, and assess rationality and feasibility of the reform. We found that the projected scope and schedule of changes in the Ukrainian health system give promising prognosis regarding its final effect.

Conclusions

The final success of health reform in Ukraine is dependent on a number of factors, including the financial foundation arising of economic stability of the country, balance assurance between public and private spending for health and ability to eliminate the long-lasting practices, particularly when they are connected with activities of lobbying groups occupying particular positions in the health system. A consequence of actions taken by the political decision-makers in the longer perspective are also to highly determine the reform’s chances for success.

     

Exploring motivations behind pollution-mask use in a sample of young adults in urban China

Background

Wearing a pollution mask is an effective, practical, and economic way to prevent the inhalation of dangerous particulate matter (PM). However, it is not uncommon to observe negligence in adopting such behaviour, and this especially among young segments of the population. Using the Theory of Planned Behaviour (TPB) as conceptual framework, this study explores the role of socio-cognitive factors that affect the decision of wearing a pollution mask in the context of young educated people. This is done by selecting a sample of college students in urban China, a country that has seen air quality as one of the major challenges in the last decades. While young urban college students might be expected to be receptive to standard attempts to be influenced through reason-based cognitive stimuli, it is often found that this is not the case. The empirical analysis was articulated it in two steps. Structural Equation Modelling (SEM) was first used to examine the relationships among the conceptual constructs derived from the TPB conceptual model, and second Step-Wise Ordinary Least Squares Regressions (SWOLS) were employed to observe the partial effect played by each item on the decision to wear a mask.

Results

Results show that, while reason-based stimuli play a role, attitude, social norm, and self-efficacy were the most important predictors of the behavioural intention (p?<?0.01). The role of past behaviour was also acknowledged as strongly associated with the dependent variable (p?<?0.01). Overall, the likelihood of wearing a pollution mask increases with the importance of others socio-cognitive and psychological factors, which could help understand behavioural biases, and explain the relative role of several mechanisms behind the decision to wear a mask.

Conclusions

While tackling pollution requires multiple and synergic approaches, encouraging self-prevention using pollution mask is a simple and effective action, implementable at negligible costs. Resistance among younger, well-educated cohorts to wear masks can be overcome by stressing the social desirability of action and the sense of empowerment derived from its usage. This study has the potential to inform policies aimed at changing suboptimal behavioural attitudes by identifying triggers for change, and it could serve in improving the tailoring of health promotion messages aimed at nudging healthy behaviour.

     

Stronger together: midwifery twinning between Tanzania and Canada

This article describes a twinning relationship between the Canadian Association of Midwives (CAM) and the Tanzania Midwives Association (TAMA). It argues that the twinning relationship strengthened both associations. The article briefly reviews the existing literature on professional associations and association strengthening to demonstrate that professional associations are a vital tool for improving the performance of healthcare workers and increasing their capacity to contribute to national and international policy-making. It then suggests that midwifery associations are particularly significant given the frequent professional marginalization of midwives. The article then describes in depth the relationship between CAM and TAMA, highlighting the accomplishments of the twinned partners, and analyzing the factors that contributed to the success of the relationship. The findings demonstrate that twinning can successfully strengthen associations, increasing their ability to support their membership, care for the public, and shape national policy-making. The article therefore proposes twinning as a successful and cost-effective model for encouraging the growth of the midwifery profession.     

Youth health outcomes from the Connect-to-Protect coalitions to prevent adolescent HIV infections

We assessed the relationships among HIV-related social and behavioral outcomes resulting from an adolescent-focused HIV structural change initiative in eight urban sites operating Connect-to-Protect coalitions. Over a 4-year period, annual cross-sectional panels of adolescents (N = 2248) completed an audio-computer-assisted interview, providing data on satisfaction with their communities as adolescent-supportive environments, internalized HIV stigma, lifetime HIV-testing, lifetime sexual risk-taking and number of sexual partners in the prior year. We used structural equation modeling to estimate hypothesized links between time since coalition mobilization to our social and behavioral outcomes. Over the 4 years, adolescents perceived their communities to become more supportive (p < .05). Positive perceptions of community support were associated with lower lifetime HIV sexual risk (p < .05). The effect of time on risk behavior was mediated by perceptions of community support. Stigma was unchanged over time. Stigma had damaging effects on risk behavior, effects which were also mediated by perceptions of community support. Special efforts are needed to address the deleterious effect of HIV stigma on high-risk urban adolescents.     

Prevalence of hidden carbon monoxide poisoning in auto service workers; a prospective cohort study

Background

Carbon monoxide (CO) is formed as a result of the incomplete burning of hydrocarbon-containing fuels such as natural gas, coal, liquid petroleum gas, and wood. CO is a colorless, odorless, and poisonous gas that produces various acute and chronic effects in CO-exposed people. In this study, we aimed to measure CO levels in auto care repairmen with chronic CO-related illnesses using a serial, non-invasive method.A prospective cohort study.

Methods

A total of 99 people from six different auto-repair services were included in the study. Carboxyhemoglobin (COHb) levels were measured at four different times with 2-hour intervals starting at 08:00 AM. Data concerning employees’ ages, working hours, smoking statuses, and types of home heating fuel were collected. A control group of 100 cases was created based on this data. The measurements were done on the control group in the morning with a Masimo Rad-57 CO-oximeter.

Results

The highest mean (± SD) COHb value was 7.04%?±?3.32% after the third measurement. The mean value for the control group was 1.61%?±?1.43%. A statistically significant difference between the groups was found for each value.

Discussion

We determined that the risk of being affected by CO is high in buildings in which the auto services were located. The effects of chronic or prolonged exposure to low amounts of CO were found to be ambiguous. However, in some studies, it was found that low-grade CO exposure could lead to coronary artery disease and some neurological complications. Therefore, it is necessary to be careful about the health of employees who have been exposed to CO.

Conclusions

We concluded that there is a need for more detailed studies concerning chronic CO poisoning. Also, in workplaces in which there is high exposure to CO, proper workplace safety measures should be taken to reduce this gas’s harmful effects to employees.

     

Leadership position and physician visits – results of a nationally representative longitudinal study in Germany

Background

So far, studies within the occupational field have largely concentrated on working conditions and job stressors and staff members’ or subordinate health. Only a few have focused on managers in this context, but studies are missing that explicitly look at the relation between leadership position and health care use (HCU). Thus, the purpose of this study was to examine the potential effects of a change in leadership position on HCU in women and men longitudinally.

Methods

Data were drawn from a nationally representative longitudinal study in Germany (German Socio-Economic Panel, GSOEP). Data from 2009 and 2013 were used. Leadership position was divided into (i) top management, (ii) middle management, (iii) lower management, and (iv) a highly qualified specialist position. The number of physician visits in the preceding 3 months were used to quantify HCU (n?=?2140 observations in regression analysis; 69% male).

Results

Adjusting for various potential confounders (e.g., age, self-rated health, chronic conditions, and personality factors), Poisson FE regression analysis revealed that changes from a highly qualified specialist position to the top management were associated with a decrease in the number of physician visits in men (β?=?.47, p?<?.05), but not in women. Gender differences (gender x leadership position) were significant.

Conclusions

Findings of this study emphasize the impact of leadership positions on the number of physician visits in men. Further study is required to elucidate the underlying mechanisms.