A quantitative analysis of the menopause experience of Indian women living in Sydney

AIMS: To examine the experience of menopause in Indian women (aged 45-65 years) in Sydney, and the relationship between sociodemographic factors and menopausal symptoms, and also to explore the cultural context. METHODS: Two hundred and three women were interviewed about their menopausal experiences in the preceding week using the 29-item Menopause-Specific Quality of Life questionnaire. RESULTS: The mean age of menopause for Indian women was found to be earlier than in other groups in the published literature, at 48.21 years. While there were higher scores for physical symptoms than for other symptoms, and there were significant differences between perimenopausal women and the others, it was found that the prevalence of classical menopausal symptoms was lower in Indian women than that found in Caucasians. However, physical and several psychological symptoms were found to be more prevalent than the usual vasomotor symptoms. Unemployed women and women with a tertiary level of education were found to experience a significantly higher score for all symptoms in our sample. CONCLUSIONS: Lower scores of menopause symptoms indicate that Indian women have fewer complaints of symptoms and a positive attitude towards menopause. Somatic symptoms are multifactorial in nature and could be because of health problems associated with ageing, midlife crises and cultural influences. Further detailed studies could examine the important relationship between cultural lifestyle factors and climacteric symptoms.     

An association test of the spatial distribution of rare missense variants within protein structures identifies Alzheimer's disease–related patterns

More than 90% of genetic variants are rare in most modern sequencing studies, such as the Alzheimer''s Disease Sequencing Project (ADSP) whole-exome sequencing (WES) data. Furthermore, 54% of the rare variants in ADSP WES are singletons. However, both single variant and unit-based tests are limited in their statistical power to detect an association between rare variants and phenotypes. To best use missense rare variants and investigate their biological effect, we examine their association with phenotypes in the context of protein structures. We developed a protein structure–based approach, protein optimized kernel evaluation of missense nucleotides (POKEMON), which evaluates rare missense variants based on their spatial distribution within a protein rather than their allele frequency. The hypothesis behind this test is that the three-dimensional spatial distribution of variants within a protein structure provides functional context to power an association test. POKEMON identified three candidate genes (TREM2, SORL1, and EXOC3L4) and another suggestive gene from the ADSP WES data. For TREM2 and SORL1, two known Alzheimer''s disease (AD) genes, the signal from the spatial cluster is stable even if we exclude known AD risk variants, indicating the presence of additional low-frequency risk variants within these genes. EXOC3L4 is a novel AD risk gene that has a cluster of variants primarily shared by case subjects around the Sec6 domain. This cluster is also validated in an independent replication data set and a validation data set with a larger sample size.

High-throughput DNA sequencing of diverse humans has identified millions of genetic variants, the vast majority of which are exceptionally rare. A survey of ∼60,000 individuals from the Exome Aggregation Consortium (ExAC) found that out of ∼7 million variants, 99% have a frequency <1% and 54% are singletons (Taliun et al. 2021). Similarly, in the Alzheimer''s Disease Sequencing Project (ADSP) whole-exome sequencing (WES) of ∼10,000 individuals, 97% of identified variants have a minor allele frequency <1%, and 23% are singletons (Butkiewicz et al. 2018). However, the effect of most rare variants on diseases of interest remains unknown because of insufficient statistical power to detect the associations between these variants and phenotypes.We hypothesized that rare missense variants contribute to common diseases by disrupting the protein function and are likely to form clustered or dispersed patterns within protein structures when examined in population-based studies. Therefore, incorporating spatial context will improve rare variant association tests. Prior studies have shown that missense variants show nonrandom patterns in protein structures, such as cancer-associated hotspot regions with a high density of missense somatic mutations (Tokheim et al. 2016). Our group (Sivley et al. 2018) also found that germline causal missense variants for Mendelian diseases show nonrandom patterns in three-dimensional (3D) space. These patterns include clusters that likely reflect disruption of a key functional region and dispersions that likely reflect depletion of variants within a sensitive protein core.To test this hypothesis within sequencing studies of disease traits, we developed a kernel function to quantify genetic similarity among individuals by using protein structure information. When two individuals have different missense variants distal in genomic coordinates but close in 3D protein structure, these individuals will be assigned a high genetic similarity through our kernel function. When applied over an entire data set, our kernel function captures differences in the spatial patterns of rare missense variants among cases and controls or over continuous traits. Using a statistical framework similar to SKAT (Wu et al. 2011), we test the association of rare variants with quantitative and dichotomous phenotypes using this structure-based kernel. We call this approach protein optimized kernel evaluation of missense nucleotides (POKEMON). We validated that POKEMON can identify trait associations with spatial patterns formed by missense variants both in simulation studies and real-world data.     

Soil-Transmitted Helminthic Infections and Geophagia among Pregnant Women in Jimma Town Health Institutions,Southwest Ethiopia

BackgroundPregnancy is a key step for human''s reproduction and continuity of generation. Pregnant women are among at risk groups for the infection of soil-transmitted helminths (STHs). STHs are highly prevalent in low- and middle-income countries due to the deprived environmental sanitation and personal hygiene. Eating soil (geophagia) is also commonly practiced by pregnant women, particularly in developing countries. The aim of this study was to determine the prevalence of STHs and geophagia, and to assess associated factors among pregnant women in Jimma, Southwest Ethiopia.MethodsA cross sectional study was conducted among 407 pregnant women attending antenatal care (ANC) at different health facilities located in Jimma Town. Data related to sociodemographic and geophagia practice was collected using a structured questionnaire and STH infections status was determined by using McMaster technique.ResultsA total of 407 pregnant women were included in this study. The overall prevalence of any STHs was 19.7% (80/407). Ascaris lumbricoides was the most prevalent 45(56.2%), followed by Trichuris trichiura 19(23.8%) and hookworms 12(15%). There were 4(5%) of double infection with A. lumbricoides and T. trichiura. Overall, 71 (17.4%) of the pregnant women responded to practice geophagia. STHs infection was significantly higher among geophagic pregnant women (p<0.01) and pregnant women who practiced geophagia were 3 times more likely (OR 2.9, 95% CI 1.3–4.2) to have the STHs compared to non-geophagic. Out of those who claimed soil eating habits, 59.1% preferred reddish soil type. Geophagia practice was significantly higher during the third trimester as compared to first and second (p<0.05).ConclusionGeophagia is a risky behavior and this study showed a significant association of geophagia practice with STH infections, although the causal relation could not be established.     

Novel Hendra Virus Variant Circulating in Black Flying Foxes and Grey-Headed Flying Foxes,Australia

A novel Hendra virus variant, genotype 2, was recently discovered in a horse that died after acute illness and in Pteropus flying fox tissues in Australia. We detected the variant in flying fox urine, the pathway relevant for spillover, supporting an expanded geographic range of Hendra virus risk to horses and humans.     

Balancing high accrual and ethical recruitment in paediatric oncology: a qualitative study of the 'look and feel' of clinical trial discussions

Background  

High accrual to clinical trials enables new treatment strategies to be tested rapidly, accurately and with generalisability. Ethical standards also must be high so that participation is voluntary and informed. However, this can be difficult to achieve in trials with complex designs and in those which are closely embedded in clinical practice. Optimal recruitment requires a balance of both ethical and accrual considerations. In the context of a trial of stratified treatments for children with acute lymphoblastic leukaemia (UKALL2003) we examined how recruitment looked to an observer and how it felt to the parents, to identify how doctors' communication could promote or inhibit optimal recruitment.     

Report of the Council on Scientific Affairs of the American Medical Association: ultrasound evaluation of the fetus.

Ultrasound evaluation of the fetus has become a vital part of prenatal care not only to detect abnormalities of fetal growth, but to diagnose congenital anomalies, hydatidiform mole and ectopic pregnancy, to assess fetal well-being, and finally to provide ultrasound guidance for invasive procedures. This article will discuss the role of fetal ultrasonography as we head into the 1990s, the changing concepts of indications for ultrasound scanning, the increasing sophistication of the technique, and the types of anomalies detected by this imaging method.     

Intravenous immunoglobulin in HIV infection: evidence for the efficacy of treatment.

Eight children with symptoms of HIV infection were treated for 12-26 months (median 14 months) with infusions of intravenous immunoglobulin (200 mg/kg) every three weeks. Significant improvement was noted in all children in terms of weight gain, number of infectious episodes, and days spent in hospital. This resulted in a 49% saving in cost on treatment compared with costs accrued previously during inpatient admissions. Immunoglobulin concentrations, which were raised at the start of treatment were not altered, and T4 counts continued to decline slowly. HIV core antigen was detected in four children before treatment, but all became core antigen negative after treatment was commenced, this effect being sustained in three. Intravenous immunoglobulin therefore has major clinical benefit, and by reducing viral activity may delay disease progression.     

Gynaecological Complications of Women Treated with Tamoxifen for Breast Cancer

Summary: We present 6 cases illustrating some of the gynaecological complications associated with tamoxifen treatment of women with breast cancer. The first 2 represent cases of myometrial hypertrophy secondary to tamoxifen use, a postmenopausal woman and a premenopausal women with recurrent carcinoma of the breast. The third is a case of probable ovulation induction in a perimenopausal woman with recurrent breast cancer who was commenced on tamoxifen 20 mg daily. The other 3 cases illustrate some of the endometrial effects associated with tamoxifen therapy in women with a history of breast cancer, namely cystic glandular hyperplasia, endometrial polyps and endometrial cancer.     

Effect of gestational age on baseline fetal heart rate during the third trimester of pregnancy

Analysis of the fetal heart rate in 3,127 reactive nonstress tests revealed that the baseline rate decreased significantly between 28 and 41 weeks' gestation (6.4 beats per minute [4.5%]). Analysis of 235 women with two tests at least four weeks apart revealed that while the majority (51.1%) demonstrated a decrease, 26.8% experienced a rise in the baseline rate during the testing interval.