Prediction of Maternal Cytomegalovirus Serostatus in Early Pregnancy: A Retrospective Analysis in Western Europe

Background

Cytomegalovirus (CMV) is the most prevalent congenital viral infection and thus places an enormous disease burden on newborn infants. Seroprevalence of maternal antibodies to CMV due to CMV exposure prior to pregnancy is currently the most important protective factor against congenital CMV disease. The aim of this study was to identify potential predictors, and to develop and evaluate a risk-predicting model for the maternal CMV serostatus in early pregnancy.

Methods

Maternal and paternal background information, as well as maternal CMV serostatus in early pregnancy from 882 pregnant women were analyzed. Women were divided into two groups based on their CMV serostatus, and were compared using univariate analysis. To predict serostatus based on epidemiological baseline characteristics, a multiple logistic regression model was calculated using stepwise model selection. Sensitivity and specificity were analyzed using ROC curves. A nomogram based on the model was developed.

Results

646 women were CMV seropositive (73.2%), and 236 were seronegative (26.8%). The groups differed significantly with respect to maternal age (p = 0.006), gravidity (p<0.001), parity (p<0.001), use of assisted reproduction techniques (p = 0.018), maternal and paternal migration background (p<0.001), and maternal and paternal education level (p<0.001). ROC evaluation of the selected prediction model revealed an area under the curve of 0.83 (95%CI: 0.8–0.86), yielding sensitivity and specificity values of 0.69 and 0.86, respectively.

Conclusion

We identified predictors of maternal CMV serostatus in early pregnancy and developed a risk-predicting model based on baseline epidemiological characteristics. Our findings provide easy accessible information that can influence the counseling of pregnant woman in terms of their CMV-associated risk.     

Early Interactions Between Mothers and Their Medically Fragile Infants

The purpose of this study was to examine the interactions of 56 medically fragile infants and their mothers and to determine the influence of infant age, neurological status, maternal education, ethnicity, and observation location on these interactions. The interactions were observed for about 1 hr every 2 months while in the hospital, 1 month after hospital discharge, and at 6 months corrected age. The age of the infants had the greatest effect on the interaction. As infants grew older, mothers spent less time feeding, involved, holding, in body contact, looking, rocking, gesturing, and touching. However, mothers talked more, and played more with older infants. Older medically fragile infants were alert more, vocalized more, and slept less. Only one variable was directly affected by neurological status: Mothers moved neurologically normal infants more often. The neurologically normal and compromised groups were also more similar at older ages than younger ages in the percentage of time the mother was involved and the infant vocalized. Mothers with more years of education fed their infants more and looked at them more often, and minority mothers talked to their infants less and moved them more.     

Effect of Breastfeeding Promotion on Early Childhood Caries and Breastfeeding Duration among 5 Year Old Children in Eastern Uganda: A Cluster Randomized Trial

BackgroundAlthough several studies have shown short term health benefits of exclusive breastfeeding (EBF), its long term consequences have not been studied extensively in low-income contexts. This study assessed the impact of an EBF promotion initiative for 6 months on early childhood caries (ECC) and breastfeeding duration in children aged 5 years in Mbale, Eastern Uganda.MethodsParticipants were recruited from the Ugandan site of the PROMISE- EBF cluster randomised trial (ClinicalTrials.gov no: {"type":"clinical-trial","attrs":{"text":"NCT00397150","term_id":"NCT00397150"}}NCT00397150). A total of 765 pregnant women from 24 clusters were included in the ratio 1:1 to receive peer counselled promotion of EBF as the intervention or standard of care. At the 5 year follow-up, ECC was recorded under field conditions using the World Health Organization’s decayed missing filled tooth (dmft) index. Adjusted negative binomial and linear regression were used in the analysis.ResultsMean breastfeeding duration in the intervention and control groups (n=417) were 21.8 (CI 20.7–22.9) and 21.3(CI 20.7–21.9) months, respectively. The mean dmft was 1.5 (standard deviation [SD] 2.9) and 1.7 (SD 2.9) in the intervention and control groups, respectively. Corresponding prevalence estimates of ECC were 38% and 41%. Negative binomial regression analysis adjusted for cluster effects and loss-to-follow-up by inverse probability weights (IPW) showed an incidence-rate ratio (IRR) of 0.91 (95% CI 0.65–1.2). Comparing the effect of the trial arm on breastfeeding duration showed a difference in months of 0.48 (-0.72 to 1.7).ConclusionPROMISE EBF trial did not impact on early childhood caries or breastfeeding duration at 5 years of age. This study contributes to the body of evidence that promotion of exclusive breastfeeding does not raise oral health concerns. However, the high burden of caries calls for efforts to improve the oral health condition in this setting.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00397150","term_id":"NCT00397150"}}NCT00397150     

Outpatient Termination of Early Pregnancies Using Syringe and Plastic Cannula

Using a 50 ml syringe and a Karman-type cannula-curette, outpatient therapeutic abortions were done in 543 women who were not more than eight weeks pregnant. All patients received paracervical block analgesia and atropine was given intravenously to minimize vagal reactions. In five women (0.9 percent) pregnancies were missed by the procedure, and in 13 women (2.4 percent) abortions were incomplete. In only one patient did a significant postoperative pelvic infection occur. Twenty-seven women (4.9 percent) were not pregnant; the initiation of routine urine pregnancy testing reduced the percentage of those who were nongravid. The procedure using syringe and plastic cannula is safe, well tolerated and has reduced therapeutic abortion costs.     

Breastfeeding and Snoring: A Birth Cohort Study

Objective

To investigate the relationship between breastfeeding and snoring in childhood.

Methods

In a cohort of children with a family history of asthma who were recruited antenatally we prospectively recorded data on infant feeding practices throughout the first year of life. Snoring status and witnessed sleep apnea were measured at age 8 years by parent-completed questionnaire. Associations were estimated by logistic regression with, and without, adjustment for sets of confounders designed to exclude biasing effects.

Results

Habitual snoring was reported in 18.8% of the sample, and witnessed apnea in 2.7%. Any breastfeeding for longer than one month was associated with a reduced risk of habitual snoring at age 8 (adjusted OR 0.48, 95% CI 0.29 to 0.81) and duration of breastfeeding was inversely associated with the prevalence of habitual snoring (adjusted OR 0.79, 95% CI 0.62 to 1.00). Any breastfeeding for longer than 1 month was associated with a lower risk of witnessed sleep apnea (adjusted OR 0.17, 95% CI 0.04 to 0.71). The protective associations were not mediated by BMI, current asthma, atopy or rhinitis at age 8 years.

Conclusions

Breastfeeding for longer than one month decreases the risk of habitual snoring and witnessed apneas in this cohort of children with a family history of asthma. The underlying mechanism remains unclear but the finding would be consistent with a beneficial effect of the breast in the mouth on oropharyngeal development with consequent protection against upper airway dysfunction causing sleep-disordered breathing.     

Early Exposure to Respiratory Allergens by Placental Transfer and Breastfeeding

The relationship between allergen exposure and the onset of or protection from allergic diseases remains unclear. Many factors could be related to immunological responses, such as the age when the exposure occurs, type of allergen, timing, dose, and allergen route. In this study, we investigated whether exposure to respiratory allergens could occur in pregnancy or early life. In particular, we assessed whether Der p 1 and Blo t 5, as well as specific antibodies against these allergens, could be detected in 90 paired cord blood and colostrum samples. Der p 1 was detected in 58.6% of colostrum and 29% of cord blood samples, whereas Blot 5 was positive in 41.3% and 9.6% of the samples, respectively. Similar to specific IgA, which could be detected in all samples for both mites, specific IgG was found in a high number of colostrum samples, 93.5% and 94.8% for Dp and Bt, respectively. Although allergens were not detected in all cord blood samples, a high percentage of them (≥95%) were positive for specific IgM to both mites in cord blood samples, suggesting that neonates can be exposed and sensitized to airborne allergens during pregnancy. Many studies have attempted to correlate allergen exposure or its prevention in early infancy with the onset of or protection from allergic diseases. However, conflicting and inconsistent data do not show a clear correlation with or suggest a way to prevent allergen sensitization. Nevertheless, these unconvincing results could be better understood if the relationship with many aspects of allergen exposure after pregnancy could be clarified. Thus, it is necessary to address basic issues related to allergen exposure, including the development of reproducible, standardized and reliable methods, and to determine how and where the exposure occurs.     

Platelet Count and Early Outcome in Patients with Spontaneous Cerebellar Hemorrhage: A Retrospective Study

Introduction

The importance of coagulation, hematology, and biochemical variables have been investigated in the stroke population but have not been systemically surveyed in cerebellar hemorrhage (CH) population. The aim of the study was to explore the predictive value of these factors for early outcome in this population.

Materials and Methods

Eighty patients with acute spontaneous CH were retrospectively analyzed. Clinical and laboratory data were collected on admission for analysis. The patients were divided by Glasgow outcome scale (GOS) score at discharge into the good outcome group (GOS score 4 or 5) and the poor outcome group (GOS score 1, 2, or 3). The association between early outcome and clinical or laboratory variables were investigated by binary logistic regression.

Results

There were 46 (57.5%) patients in the poor outcome group and 34 (42.5%) in the good outcome group. The platelet count (PC) was significantly lower in the poor outcome group (187.3 ± 53.0 × 10⁹/l) compared with good outcome group (244.9 ± 63.9 × 10⁹/l) (p < 0.001). Moreover, PC (OR 0.97; p = 0.004) was the strong predictor with poor early outcome.

Conclusions

We firstly show that lower PC is the independent predictor for poor early outcome in patients with spontaneous CH.     

A Study of Changes in Uterine Leucocytes During Early Pregnancy in the Mouse-vole Interspesific Pregnancies

Mouse and vole embryos were allogeneically and xenogeneically transferred into pseudopregnant CD-1 and immunodeficient （scid） female mice, and we investigated the distribution of uterine leucocytes cells in the implantation sites on days 5,6,and 7 of pregnancy. Macrophages were evenly distributed in the endometrium on days 5 N 7. Neutrophils were rarely seen on days 5 ~ 7, but lymphoeytes were found throughout the endometrium,often in groups associated with glands or the luminal epithelium. The number of uNK cells increased markedly at the mesometrial triangle and the outer decidual area in the CD-1 uteri containing vole embryos; by contrast, scid uteri having vole embryos showed almost the same number as those having mouse embryos. Mast cells were present in large numbers at the myometrium,but rarely in the decidua in all types of pregnant uteri. Cells at the myometrium were more numerous in xenogeneic than in allogeneic transfer. Many mast cells appeared in the inner decidua where xenogeneically transferred vole embryos were dead and aborted. These results suggest the possibility that uterine leucocytes mediate various immunological events in the mouse-vole interspesific pregnancies.     

High Uptake of Exclusive Breastfeeding and Reduced Early Post-Natal HIV Transmission

Background

Empirical data showing the clear benefits of exclusive breastfeeding (EBF) for HIV prevention are needed to encourage implementation of lactation support programs for HIV-infected women in low resource settings among whom replacement feeding is unsafe. We conducted a prospective, observational study in Lusaka, Zambia, to test the hypothesis that EBF is associated with a lower risk of postnatal HIV transmission than non-EBF.

Methods and Results

As part of a randomized trial of early weaning, 958 HIV-infected women and their infants were recruited and all were encouraged to breastfeed exclusively to 4 months. Single-dose nevirapine was provided to prevent transmission. Regular samples were collected from infants to 24 months of age and tested by PCR. Detailed measurements of actual feeding behaviors were collected to examine, in an observational analysis, associations between feeding practices and postnatal HIV transmission. Uptake of EBF was high with 84% of women reporting only EBF cumulatively to 4 months. Post-natal HIV transmission before 4 months was significantly lower (p = 0.004) among EBF (0.040 95% CI: 0.024–0.055) than non-EBF infants (0.102 95% CI: 0.047–0.157); time-dependent Relative Hazard (RH) of transmission due to non-EBF = 3.48 (95% CI: 1.71–7.08). There were no significant differences in the severity of disease between EBF and non-EBF mothers and the association remained significant (RH = 2.68 95% CI: 1.28–5.62) after adjusting for maternal CD4 count, plasma viral load, syphilis screening results and low birth weight.

Conclusions

Non-EBF more than doubles the risk of early postnatal HIV transmission. Programs to support EBF should be expanded universally in low resource settings. EBF is an affordable, feasible, acceptable, safe and sustainable practice that also reduces HIV transmission providing HIV-infected women with a means to protect their children''s lives.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00310726","term_id":"NCT00310726"}}NCT00310726     

A Neural Population Model Incorporating Dopaminergic Neurotransmission during Complex Voluntary Behaviors

Assessing brain activity during complex voluntary motor behaviors that require the recruitment of multiple neural sites is a field of active research. Our current knowledge is primarily based on human brain imaging studies that have clear limitations in terms of temporal and spatial resolution. We developed a physiologically informed non-linear multi-compartment stochastic neural model to simulate functional brain activity coupled with neurotransmitter release during complex voluntary behavior, such as speech production. Due to its state-dependent modulation of neural firing, dopaminergic neurotransmission plays a key role in the organization of functional brain circuits controlling speech and language and thus has been incorporated in our neural population model. A rigorous mathematical proof establishing existence and uniqueness of solutions to the proposed model as well as a computationally efficient strategy to numerically approximate these solutions are presented. Simulated brain activity during the resting state and sentence production was analyzed using functional network connectivity, and graph theoretical techniques were employed to highlight differences between the two conditions. We demonstrate that our model successfully reproduces characteristic changes seen in empirical data between the resting state and speech production, and dopaminergic neurotransmission evokes pronounced changes in modeled functional connectivity by acting on the underlying biological stochastic neural model. Specifically, model and data networks in both speech and rest conditions share task-specific network features: both the simulated and empirical functional connectivity networks show an increase in nodal influence and segregation in speech over the resting state. These commonalities confirm that dopamine is a key neuromodulator of the functional connectome of speech control. Based on reproducible characteristic aspects of empirical data, we suggest a number of extensions of the proposed methodology building upon the current model.     

Analysis of Early Postoperative Pain in the First and Second Knee in Staged Bilateral Total Knee Arthroplasty: A Retrospective Controlled Study

Objective

A retrospective analysis of early postoperative pain in the first and second knee in staged bilateral total knee arthroplasty (TKA) to provide a clinical evidence for the change of analgesic strategy.

Methods

From January 2009 to January 2013, 87 cases which meet the inclusion criterion were retrospectively reviewed. In stage TKA, the postoperative pain in the first and second knee at 24h, 48h, 72h after operation were compared using the visual analogue scale (VAS) score in the rest and maximum knee flexion position. The difference in pain scores (ΔVAS) was also compared between the second and first knee at different time intervals (less than 6 months, 6-12 months, more than 12 months).

Results

The VAS scores in the second knee were significantly higher than those in the first knee at 24h, 48h after surgery, but with no difference at 72h. The ΔVAS in the group of less than 6 months was significantly higher than of those more than 6 months, and there was no difference in ΔVAS between group of 6-12 months and group of more than 12 months.

Conclusions

Patient receiving staged bilateral TKA experiences greater postoperative pain within 48h after operation in the second knee than in the first knee, which can provide a clinical evidence to enhance the analgesic strategy in the second operation of the staged bilateral TKA. And for the management of postoperative pain in staged bilateral TKA, it’s better to recommend that the interval between two operations should be more than 6 months, which may reduce the postoperative pain in the second knee, improve patient satisfaction, and speed up patient‘s rehabilitation process.     

Thionamide-induced Agranulocytosis: A Retrospective Analysis of 36 Patients With Hyperthyroidism

ObjectiveAgranulocytosis is a rare but serious adverse drug reaction (ADR) of thionamide antithyroid drugs (ATDs). We explored the characteristics of ADRs in patients with hyperthyroidism.MethodsThis retrospective study included 3558 inpatients with Graves disease treated in a Class A Grade 3 hospital between 2015 and 2019. The clinical presentation and laboratory workup of patients with antithyroid drug (ATD)-induced agranulocytosis was analyzed.ResultsAgranulocytosis was thought to be caused by ATDs in 36 patients. The hospital length of stay was 12 (10-16) days, and hospitalization costs were approximately $2810.89 ($2156.50-$4164.67). The median duration of ATD therapy prior to agranulocytosis development was 30 (20-40) days. Fever (83.33%) and sore throat (75%) were the most common symptoms as early signs of agranulocytosis. The lowest neutrophil counts were 0.01 (0.00-0.03) × 10⁹/L and 0.14 (0.02-0.29) × 10⁹/L in the methimazole and propylthiouracil groups, respectively (P = .037). The recovery times of agranulocytosis were 9.32 ± 2.89 days and 5.60 ± 4.10 days in the methimazole and propylthiouracil groups, respectively (P = .016). Patients with severe agranulocytosis required a longer time to recover (P < .001) and had closer to normal serum thyroxine and triiodothyronine levels. The interval between the first symptom of agranulocytosis and ATD withdrawal was 1 (0-3) day.ConclusionsPatients with agranulocytosis needed a long hospital length of stay and incurred high costs. Methimazole was prone to causing a more serious agranulocytosis than propylthiouracil. High thyroid hormone was unlikely to play a role in adverse drug reactions. Patient education is important.     

Prosocial Behaviors during School Activities among Child Survivors after the 2011 Earthquake and Tsunami in Japan: A Retrospective Observational Study

Background

The 2011 Japan massive tsunami traumatized many children. The aim of this study was to assess changes in strengths and difficulties experienced in home and school by among surviving children after the 2011 tsunami, in comparison with published normal Japanese data.

Methods

In November 2012 (20 months after the disaster) and September 2013 (30 months after the disaster), the Strengths and Difficulties Questionnaire (SDQ), a questionnaire on children''s strengths and difficulties in home and school activities, were distributed to 12,193 and 11,819 children, respectively. An effective response of children 20 months and 30 month after the disaster was obtained in 10,597 children (86.9%), and 10,812 children (91.4%), respectively. The SDQ scores evaluated by parents and teachers were compared with published normal Japanese SDQ scores.

Results

The SDQ scores (emotional problems, conduct problems, hyperactivity/inattention, peer relationship problems, and total difficulty score) evaluated by parents of children in the 4th to 9th grade who were evaluated after 30 and 20 months were significantly high compared with the published normal data of children without traumatic experiences (all P<0.001). The SDQ scores (prosocial behavior) evaluated by teachers of children in the 4th to 9th grade who were evaluated after 30 and 20 months were significantly low compared with the published normal data of children without traumatic experiences (all P<0.001).

Conclusions

This study showed that the experience of the disaster affected those children with prosocial behaviors towards teachers and friends at school. However, no significant changes (in their prosocial attitude) had been seen at home, where they continued to keep their respect and caring feelings for parents. These results indicate that for accurate diagnosis, clinicians should not only evaluate these children''s daily activities at home but also try to objectively assess their daily activities at school.     

Analysis and Organization of Protein Sequence Data: A Retrospective Spanning Four Decades

Protein sequence data are as useful and valuable today as was envisioned by pioneering sequencers and by the organizers of the first sequence database. Sequence analysis was first the province of specialists who developed search, comparison, and tree-building methods. Microcomputers, communication satellites, and the Internet have made these methods accessible to any scientist. The rapid increase in the data has driven a succession of changes in how databases are compiled, distributed, and accessed. Large public databases have become international collaborations. Although they need to develop still more efficient ways to accumulate, organize, annotate, and standardize huge amounts of data, inadequate support is available for such efforts. Thus there will be greater reliance on direct input from the scientific community. The World Wide Web is essential but not sufficient for integrated access to related databases.     

Setting Pesticide Reference Doses: A Retrospective Analysis Examining Key Data and Choices

Toxicity tests are widely used to set “acceptable” levels of chemical exposure. Different organizations have identified a base set of tests specifying a mix of endpoints, durations, and species to be tested. A specific test and endpoint is chosen as the basis for calculation of human health risk values like reference doses (RfDs). This study empirically evaluates the data and choices made in setting acute and chronic RfDs for 352 conventional pesticides. The results suggest that for Acute, Acute-Female Specific, and Chronic RfDs one test is used far more than others. Ninety-six percent of the 116 Acute Female-Specific RfDs relied on a developmental toxicity test and 78% of Chronic RfDs used the chronic bioassay. Tests in rats were used far more often than other species in all RfD calculations. For all types of RfDs a total uncertainty factor of 100 was most common although values as low as 1 and as high as 3000 were seen. These results provide insights not only into the science policy frameworks used, but also into ways toxicity testing and risk assessment may be streamlined and made more efficient.     

Pathway-based Analysis Tools for Complex Diseases:A Review

Genetic studies are traditionally based on single-gene analysis. The use of these analyses can pose tremendous challenges for elucidating complicated genetic interplays involved in complex human diseases. Modern pathway-based analysis provides a technique, which allows a comprehen- sive understanding of the molecular mechanisms underlying complex diseases. Extensive studies uti- lizing the methods and applications for pathway-based analysis have significantly advanced our capacity to explore large-scale omics data, which has rapidly accumulated in biomedical fields. This article is a comprehensive review of the pathway-based analysis methods the powerful methods with the potential to uncover the biological depths of the complex diseases. The general concepts and procedures for the pathway-based analysis methods are introduced and then, a comprehensive review of the major approaches for this analysis is presented. In addition, a list of available path- way-based analysis software and databases is provided. Finally, future directions and challenges for the methodological development and applications of pathway-based analysis techniques are dis- cussed. This review will provide a useful guide to dissect complex diseases.