Maternal and newborn health in Pakistan: risks, challenges, and the way forward

Pakistan's health indicators reflect a poor state of mother and child health, writes Dr Nadia Agha, who argues that rural women's health crises must be addressed to ensure a liveable environment for new mothers and their babies

Exploring Breast Cancer Patients’ Experiences of Struggle against Socio-Economic and Geographical Barriers in Rural Pakistan

This study offers insights into the barriers experienced by Breast Cancer (BC) patients from less privileged rural areas of Pakistan. We conducted in-depth interviews with 42 BC survivors, from the northern Sindh in southern Pakistan, to explore and analyse knowledge, geographical and financial barriers and how these barriers intersect and complicate BC patients’ lives. Results indicate that most of the women in this study were poor and their families’ health seeking behaviour was influenced by their socio-economic background; their knowledge about the disease was limited and they were unable to appropriately assess the symptoms for months, which caused delay. Based on the results, we underscore the need for increasing health education as who had a sound academic background, awareness about health as well as better social standing, accessed the treatment facility in time, approached quality healthcare services and were in a better position to cope with the aftermath of cancer. Extending the fold of quality healthcare services to less privileged areas and enabling women easy and inexpensive access to healthcare services will help in early diagnosis when treatment is affordable and chances of survival are better

Vitamin D Status in Lean and Obese Mexican American Children

Vitamin D deficiency is a worldwide problem amongst adolescents and adults, particularly in minority populations due to high skin melanin content. Melanin blocks the absorption of UVB photons, which limits natural vitamin D accumulation, requiring more dietary intake of vitamin D. Vitamin D deficiency is associated with an increased risk for chronic diseases like cardiovascular disease and diabetes mellitus. Low levels of vitamin D are inversely correlated with systemic inflammation possibly mediating the relationship between vitamin D deficiency and disease. Adequate levels of vitamin D may decrease the risks of chronic diseases, including cardiovascular disease, diabetes mellitus, common cancers, and autoimmune diseases. Obesity is associated with an increased risk of vitamin D deficiency, because vitamin D can become sequestered deep in subcutaneous adipose tissue, where it is biologically inert. In the US, Mexican-Americans are at a higher risk for both obesity and obesity-associate chronic diseases, making them an ideal research population. Objective: Investigate the relationship between serum vitamin-D status and systemic inflammation in Mexican-American children of differing obesity status. Patients and Methods: Serum vitamin D concentration will be measured using a commercially available ELISA kit. Vitamin D status will be determined using norms established by the Institute of Medicine in 2010. Serum TNF-α, IL-6, and IL-8 concentration will be measured using a Luminex Multiplex assay (Millipore Milliplex)

Corticosterone Levels in Sedentary, Wheel, and Treadmill Acclimated Mice following a Bout of Forced Treadmill Running

Murine models have been used to study the immune response to exercise under various diet and training interventions .Our laboratory has previously studied the effect of forced exercise versus voluntary exercise on fasting blood glucose measurements. However, forced exercise may result in increased corticosterone levels. This may affect glucose levels and subsequent weight gain. Male, wild-type CD-1 mice were randomly divided into the following groups: forced exercise, wheel running, and sedentary. After a 8- weeks of the intervention, all mice were placed on a treadmill and forced to run for 30 minutes. Blood was collected from the mice prior to exercise, immediately following exercise, and one hour post exercise. Plasma corticosterone levels were assessed using an ELISA. 3-color flow cytometry was used to assess blood leukocytes. We found that despite treadmill acclimation in the forced exercise group, there was no significant difference between groups in corticosterone or leukocyte levels when forced to run on a treadmill. All groups showed a spike in corticosterone levels immediately following exercise which returned to baseline at one-hour post

Exercise as a Prevention and Countermeasure to Diet-Induced Weight Gain

The purpose of this study was to evaluate the effectiveness of treadmill running at attenuating weight gain and immune dysfunction prior to or during a period of high-fat feeding in outbred CD-1 male mice. Mice were divided into four groups (N=10 mice/group): 4-weeks of treadmill running followed by 4-weeks sedentary (EX-SED), 4-weeks sedentary followed by 4 weeks of treadmill running (SEDEX), 8 weeks of treadmill running (EX), and 8 weeks sedentary (SED). After the first four weeks of the study, all groups began consumption of a high-fat diet to elicit a weight gain response. In order to track immune dysfunction, we measured peripheral blood monocytes and monocyte TLR4 expression at the conclusion of the study. We also completed a detailed analysis of body weight change over time. SED-EX was the only group that did not gain a significant amount of weight during the high-fat feeding. SED-EX had the lowest percentage of monocytes, as well as the highest total monocyte and classic subset cell surface TLR4 expression. EX and SED were not significantly different in any measurement. The present study demonstrates the importance of exercise training in counteracting the pro-inflammatory effects of diet-induced weight gain, as seen in SED-EX. Contrary to our hypothesis, exercise training prior to and throughout high-fat feeding did not prevent weight gain or attenuate the pro-inflammatory effects of weight gain. This could be due to an acclimation to the exercise intervention that blunted the anti-inflammatory effects of the exercise training during the high-fat feeding phase of the study. Similarly, exercise prior to high-fat feeding did not provide a lasting protective effect against the pro-inflammatory effects of diet-induced weight gain. Future research will endeavor to expand the current knowledge about monocyte subpopulations and to further elucidate the relationship between exercise and TLR4

Exercise Attenuates Weight Gain and Fat Accumulation in CD1- Mice Consuming a High-fat Diet

Background: Exercise training, in combination with a healthful diet, is a reliable method of weight loss or weight maintenance. It is unknown whether an exercise training program would sufficiently attenuate weight gain during chronic consumption of a high-fat diet. Purpose: Therefore, the purpose of this study was to evaluate the ability of an aerobic exercise training program to prevent excessive weight gain both before and during consumption of a high-fat diet in CD-1 male mice. Methods: Mice were divided into four groups (N=10 mice/group): 4-weeks of treadmill running followed by 6-weeks sedentary (EX-SD), 4-weeks sedentary followed by 6 weeks of treadmill running (SD-EX), 10 weeks of treadmill running (EX), and 10 weeks sedentary (SD). After the first four weeks of the study, all groups began consumption of a high-fat diet to elicit a weight gain response. The exercise program consisted of 1 hour of treadmill running 5 days/wk at ~15m/min. Body weight and body composition we measured bi-weekly. Results: EX-SD, EX, and SD gained a significant amount of both body weight and body fat after only 4 weeks of high-fat feeding (P\u3c0.05). SD-EX was the only group that did not gain a significant amount of body weight or body fat during the 6-week high-fat feeding period. Conclusions: The present study demonstrates the importance of exercise training in counteracting concurrent diet-induced weight gain, as seen in SED-EX. EX approximately matched SD in body weight gain and body fat accumulation, suggesting that exercise interventions must be progressive in order to prevent an adaptation to the training program than minimizes exercise benefits. Future research will evaluate progressive exercise training programs and their implications in various mouse models

B-cell homeostasis is maintained during long duration spaceflight

Long-duration spaceflights reportedly induce immune dysregulation, which is considered a risk to astronaut safety and mission success. Recent studies have examined the impact of spaceflight on markers of adaptive and innate immunity, but no study, to date, has comprehensively evaluated humoral immunity and serological markers of B cell function. The aim of this study was to characterize changes in B cell numbers and phenotypes, along with plasma Igs and polyclonal free light chains (FLCs)—near-“real-time” biomarkers of Ig synthesis—in response to an ~6-mo mission to the International Space Station (ISS). Whole-blood samples were collected before flight, during flight (“Early flight,” “Mid-flight,” and “Late flight”), immediately upon return, and during a recovery period (R 18, R 30/R 33, and R 60/R 66) from 23 ISS crew members. B Cell counts and phenotypes were measured throughout the duration of the mission, along with total plasma Ig and FLC levels. There was no effect of spaceflight on the number and proportion of the different B cell subsets. There was no difference in kappa FLC between preflight samples and either in-flight or recovery samples (P 0.05), and only a marginal reduction was observed in lambda FLC levels upon return to Earth (P 0.05). Furthermore, IgG and IgM remained unchanged during and after spaceflight compared with preflight values (P 0.05). Of note, plasma IgA concentrations were elevated in-flight compared with baseline and recovery values (P 0.05). These results indicate that B cell homeostasis is maintained during long-duration spaceflight, advocating for potential in-flight vaccination as viable countermeasures against viral reactivation during exploration-class missions.</p

The Effects of Exercise and a Low-Fat Diet on Monocyte TLR Expression and Disease Risk in Mice

Excess adiposity increases systemic inflammation, which is implicated in various diseases. Physical activity is a common treatment to reverse weight gain and increased disease risk; however, little evidence is available to determine if forced or voluntary exercise is more effective in mice. Such information has implications for the refinement of human exercise interventions. PURPOSE: To determine if 8-weeks of exercise combined with low-fat feeding reverses changes in disease risk, monocyte concentration and monocyte TLR2/TLR4 expression. METHODS: For 12-months, 24 CD-1 mice underwent pre-treatment, consuming either a low-fat (10% kcal from fat, N=6) or high-fat (60% kcal from fat, N=18) diet ad libitum. High-fat fed mice were randomly assigned to one of three groups (N=6/group): V-EX (low-fat chow, access to running wheel 5 d/week), F-EX (low-fat chow, forced treadmill running at 22 m/min, 60-min/d, 5 d/week), or SD (low-fat chow, no exercise). Mice pre-treated with low-fat chow served as controls (CN, N=6). Measurements were made on weekly saphenous vein blood samples using 3-color flow cytometry. Blood glucose and cholesterol concentration were analyzed weekly using a glucose and cholesterol analyzer. IPGTT was performed at baseline and week 8 and analyzed as area under the curve. RESULTS: All groups lost significant body weight over 8-weeks (P\u3c0.001). V-EX ran 4.4x more than F-EX (P\u3c0.001). There were no significant effects for blood cholesterol. CN had 26% higher glucose levels than V-EX (P=0.009). On average, there was a 59% decrease in IPGTT AUC from baseline to week 8 and V-EX decreased 37% more than CN. At week 8, monocyte concentration was 6x higher than week 1 (P=0.002). Specifically, V-EX was greater than both CN (49%) and F-EX (59%). Cell-surface TLR2 expression was significantly greater at week 6 (55%) and week 8 (23%) relative to baseline. Monocyte cell-surface TLR4 expression increased from baseline to week 8 (P\u3c0.001). CONCLUSIONS: Combining low-fat diet and exercise caused significantly more weight loss than low-fat diet alone. Overall, there was decreased insulin resistance and decreased glucose, suggesting there may have been a decrease in type II diabetes risk. Lack of difference in monocyte concentration and TLR2/4 cell-surface expression suggest the diet and exercise intervention was not long enough to elicit changes in inflammation following the long-term high-fat feeding. More research is needed to understand the time course of these changes. This study was useful in understanding what occurs during a diet and exercise intervention and in directly comparing forced and voluntary exercise

The Effects of Increasing Fat Intake on Body Composition and Blood Monocytes in CD-1 Mice

Purpose Obesity is a chronic, inflammatory state. Blood monocyte concentrations/proportions have been previously used to assess immune inflammatory status in humans. Although mouse monocytes exist in three subsets, shifts among these cells types have not been documented during a period of diet-induced weight gain. Thus, our purpose was to determine longitudinal changes in mouse monocyte subsets during 12 weeks of low, moderate or high-fat feeding. Methods: 40 CD-1 mice were randomly divided into 4 groups (N=10 per group): stock control (13.5% fat, CN), 30% fat (F30), 45% fat (F45) and 60% fat (F60). Non-lethal, saphenous vein blood samples (~70 μL) were collected bi-weekly throughout the 12-week treatment. Monocyte subsets (non-classic - CD115+/Gr-1Low, intermediate - CD115+/Gr-1Int and classic - CD115+/Gr-1High) were assessed using 3-color flow cytometry. Body weight and body composition were assessed using digital weighing and MRI scanning. Data were analyzed using a repeated measures (4 x 7 ) ANOVA; significance was set at P\u3c0.05. Results: Consuming the 30%, 45% and 60% fat diets for 12 weeks significantly increased bodyweight by 31%, 49% and 66%, respectively, compared to baseline values by (P\u3c0.05). By week 12, only F60 and F45 body weights were significantly heavier compared to stock controls (P\u3c0.05). While body fat in each treatment group was significantly higher than stock controls from weeks 2-12 (P\u3c0.05), no significant difference was detected between treatment groups. At week 12, total monocyte concentration was 123% greater in F60 compared to CN mice (P\u3c0.05) while classic, intermediate and non-classic subset concentrations were 441%, 204% and 110% greater, respectively, compared to CN (P\u3c0.05). Furthermore, the ratio of inflammatory (classic and intermediate) to non-inflammatory (non-classic) monocytes was 0.89 in F60 compared to 0.41 in CN (P\u3c0.05). Conclusions: Consumption of a 60% fat diet led to an elevation in total monocytes as well as an increased proportion of monocytes that respond to inflammatory stimuli, suggesting immune dysfunction in the blood compartment. Based on these findings, assessing blood monocyte subset characteristics may be beneficial in mouse obesity models

Mental health, physical symptoms and biomarkers of stress during prolonged exposure to Antarctica’s extreme environment

The Antarctic environment is characterized by many of the same extreme stressors as long-duration space flight (LDSE), thereby providing a useful earth-based analog for examining changes in and predictors of mental health over time. At coastal (n = 88) and inland (n = 22) Antarctic stations we tracked mental health symptoms across a nine-month period including winter-over using the Mental Health Checklist (MHCL; Bower et al., 2019). Our monthly assessment battery also examined changes in physical complaints, biomarkers of stress, and the use of different emotion regulation strategies. MHCL positive adaptation scores showed linear decreases whereas MHCL poor self-regulation scores and severity of physical symptoms increased across the study period. During-mission use of emotion regulation strategies and dehydroepiandrosterone (DHEA) levels predicted end-of-study MHCL scores, whereas trait-based psychological measures collected at the start of the mission showed little predictive utility. Results suggest that interventions and counter measures aimed at enhancing positive affect/emotion during prolonged exposure to extreme environments may be useful in reducing psychological risk