Cisplatin is a chemotherapeutic widely used in the treatment of various types of solid tumors. Acute kidney injury is the most critical dose-limiting factor in cancer patients treated with cisplatin; mitochondrial dysfunction and resultant cell damage by reactive oxygen species released from damaged mitochondria are suspected to be involved in the kidney injury. Pathological features of mitochondrial damage in relation to cisplatin-mediated nephrotoxicity, however, is not fully described. The purpose of this study was to demonstrate mitochondrial damage and clearance of damaged mitochondria by mitophagy in cisplatin-mediated nephrotoxicity. Three groups of rats received a single intraperitoneal injection of cisplatin at 20 mg/kg and were sacrificed at 24, 48 and 72 hours after the treatment. A time-dependent increase in the number of damaged renal tubules and the serum levels of blood urea nitrogen, creatinine, and mitochondrial aspartate transaminase was observed in rats after the treatment. We showed the increased numbers of swollen and fragmented mitochondria, observed by electron microscopy, and of cytochrome c oxidase IV- and 8-nitroguanosine-positive intracytoplasmic granules, detected by immunohistochemistry, in the degenerated renal tubules of the treated animals. Moreover, activated autophagy process was indicated in the degenerated renal epithelial cells, based on the findings of immunohistochemistry of microtubule-associated protein 1 light chain 3 (LC3), an autophagy marker, and lysosomal-associated membrane protein 1 (LAMP-1), a lysosome marker, and swollen and fragmented mitochondria in autophagosomes. These results suggest that mitochondrial damage and clearance of damaged mitochondria by mitophagy is involved in cisplatin-mediated nephrotoxicity.
Lower back pain (LBP) is a common health problem after natural disasters. Although some related factors have been reported, the effect of sleep disturbances on LBP is not clear. The purpose of this study was to elucidate the influence of sleep disturbances on LBP after the Great East Japan earthquake (GEJE). A panel study was conducted with the survivors of the GEJE (n = 2,295) at three and four years after the disaster using self-reported questionnaires. The changes in the presence of LBP during the two periods were assessed; LBP was characterized as either new onset or continuation of LBP. The participants’ sleep conditions were assessed, and the changes in sleep disturbances during the two periods were classified into four groups: absence, new onset, improvement, and continuation. Multivariate logistic regression models were used to analyze the association of the changes in sleep disturbance with new onset and continuation of LBP. The rates of new onset and continuation of LBP were 14.1% and 55.1%, respectively. The changes in sleep disturbances were significantly associated with new-onset and continuing LBP. Using “absence” as a reference for the change of sleep disturbance, the adjusted ORs (95% CI) for new-onset LBP were 2.19 (1.42-3.38) in “new onset,” 1.38 (0.83-2.30) in “improvement,” and 2.17 (1.50-3.15) in “continuation,” and those for continuing LBP were 1.42 (0.71-2.84) in “new onset,” 0.98 (0.55-1.74) in “improvement,” and 1.60 (1.01-2.51) in “continuation.” Careful attention should be paid to sleep disturbances to prevent and improve LBP after natural disasters.
The World Health Organization recommends continuing breastfeeding up to 2 years of age or beyond for sound growth and development of children. In Bangladesh, continuation rates for breastfeeding have recently decreased and effective measures are required to counter this downward trend. Although recent years have seen economic development and reductions in poverty, Bangladesh still has the highest rate of child marriage worldwide. Thus, we aimed to clarify the factors influencing breastfeeding continuation, especially from the perspective of inequality and mother’s age in Bangladesh, using data from the Bangladesh Demographic and Health Survey 2011. Event history analyses were performed during a 24-month follow-up period on 7,041 mothers with duration of breastfeeding as the outcome variable, with wealth index (an indicator for inequality) and mother’s age used as the main explanatory variables. The results showed that poorer mothers were on the whole more likely to continue breastfeeding through 24 months after childbirth, and younger mothers were less likely to continue breastfeeding particularly past the first year. However, both younger and older mothers continued breastfeeding to the same extent within the first year after childbirth. Mother’s age had time-varying effects on breastfeeding continuation, meaning that the effects on breastfeeding continuation were affected by the child’s age. These findings imply that policymakers should be aware that efforts to reduce child marriage may increase the rate of breastfeeding continuation beyond the first year after childbirth. In contrast, efforts at poverty alleviation, aimed at preventing child marriage, may decrease the rate irrespective of the child’s age.
Japan Environment and Children’s Study (JECS) is nationwide birth cohort study that was initiated in January 2011 to investigate the effect of environmental factors on children’s health. Soon after the JECS started, the Great East Japan Earthquake occurred on March 11, 2011, with subsequent nuclear accident at the Fukushima Daiichi Nuclear Power Plant, causing catastrophic damage in Fukushima Prefecture. After the disaster, JECS was relaunched to cover all areas in Fukushima Prefecture due to public concern. In this study, we used the results of individuals enrolled in JECS, who gave birth during 2011-2014 in Fukushima Prefecture, to elucidate pregnancy outcomes in Fukushima Prefecture. The study consisted of 12,804 maternal outcomes. We thus found that the prevalence rates of preterm birth < 37 weeks, low birth weight (LBW) < 2,500 g, and LBW < 1,500 g were 5.6 %, 9.5%, and 0.8%, respectively; these rates are in accordance with the National Vital Statistics of 2014. The proportion of major anomaly among the newborns was 1.7%, the value of which was lower than other epidemiological studies. This study also found that severe obstetrics outcomes, such as hypertensive disorder of pregnancy and placental abruption, were most frequently seen among teenage mothers with low socioeconomic status. A prefecture-wide birth cohort study following a large-scale disaster may provide valuable information for obstetric care providers and residents to improve obstetric and perinatal care for pregnant women after a disaster.
Glutathione S-transferases (GSTs), a superfamily of multifunctional enzymes, play an important role in the onset and progression of renal cell carcinoma (RCC). However, novel GST omega class (GSTO), consisting of GSTO1-1 and GSTO2-2 isoenzymes, has not been studied in RCC yet. Two coding single nucleotide polymorphisms (SNPs) supposedly affect their functions: GSTO1*C419A (rs4925) causing alanine to aspartate substitution (*A140D) and GSTO2*A424G (rs156697) causing asparagine to aspartate substitution (*N142D), and have been associated with several neurodegenerative diseases and cancers. Functional relevance of yet another GSTO2 polymorphism, identified at the 5′ untranslated (5′UTR) gene region (GSTO2*A183G, rs2297235), has not been clearly discerned so far. Therefore, we aimed to assess the effect of specific GSTO1 and GSTO2 gene variants, independently and in interaction with established risk factors (smoking, obesity and hypertension) on the risk for the most aggressive RCC subtype, the clear cell RCC (ccRCC). Genotyping was performed in 239 ccRCC patients and 350 matched controls, while plasma levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, were determined by ELISA. As a result, combined effect of all three variant genotypes exhibited almost 3-fold risk of RCC development. Additionally, this association was confirmed at the haplotype level [variant GSTO1*A/GSTO2*G (rs156697)/GSTO2*G (rs2297235) haplotype], suggesting a potential role of those variants in propensity to RCC. Regarding the gene-environment interactions, variant GSTO2*G (rs156697) homozygous smokers are at higher ccRCC risk. Association in terms of oxidative DNA damage was found for GSTO2 polymorphism in 5′UTR and 8-OHdG. In conclusion, the concomitance of GSTO polymorphisms may influence ccRCC risk.
Hearing loss is a common disease in older adults. In order to lower the prevalence of hearing loss, it is important to identify its risk factors. Although some studies have found a relationship between dental status and hearing acuity, few studies have investigated the relationship between unilateral chewing and hearing acuity. This study aimed to assess the effects of unilateral chewing on hearing acuity, with a focus on the risk of hearing loss. Eighty-one participants (aged 51-87 years) were included in the present study. Their chewing habits were determined by visual inspection. The participants were divided into two groups: the Unilateral Chewing Group (UCG; n = 43) and the Bilateral Chewing Group (BCG; n = 38). The preferred chewing side was identified for the UCG. Hearing acuity was determined using pure tone audiometry in a noise-free chamber, conducted at frequencies of 500, 1,000, 2,000, and 4,000 Hz. Hearing loss was defined as a lower hearing threshold greater than 50 dB in either ear at any frequency. Mean hearing thresholds at frequencies of 2,000 and 4,000 Hz were significantly higher, by 5.12 and 15.75 dB, respectively, for the UCG compared to the BCG (P < 0.05). The UCG had a 3.78-fold higher likelihood of suffering from hearing loss (95% confidence interval [CI]: 1.81-7.88). The results suggest that bilateral chewing could be beneficial for preventing hearing loss. This study may provide evidence to support clinical interventions aimed at reducing the risk of hearing loss in patients with unilateral chewing habits.
Mild cognitive impairment (MCI) is the prophase of dementia. MCI patients have a high risk of developing dementia. Relatively low serum albumin levels are associated with the development of several geriatric diseases, including stroke and poor cognitive performance. However, the potential relationship between serum albumin levels and MCI risk has not been fully elucidated. In the present study, we explored this relationship to increase our understanding of the pathogenesis of MCI, the finding of which may provide new ideas for the controlling of dementia. A total of 1,800 subjects who had normal cognitive function at their first health examinations (seven years ago) were retrospectively analyzed from a health database in Tianjin Medical University General Hospital. They were over 60 years old at baseline, and the follow-up period was 7 years. At the time of data collection (seven years after), 196 subjects suffered from MCI, diagnosed by symptoms and Mini-Mental State Examination. The remaining 1,604 subjects were still cognitively normal. Multivariate COX regression analysis showed that relatively low serum albumin levels at baseline (< 40.5 g/L) were associated with the increased risk of MCI (HR: 2.18, 95% CI: 1.67-2.82). Moreover, the effect of low serum albumin on the risk of MCI was further enhanced among the subjects with hypertension, diabetes, hyperlipemia, cardiovascular disease, cerebrovascular disease, high serum levels of C-reactive protein, or relatively low levels of uric acid or total bilirubin. In conclusion, relatively low serum concentrations of albumin may be an independent risk factor for MCI in elderly.
Distal symmetric polyneuropathy, represented by chronic inflammatory demyelinating polyneuropathy, is a popular neurological condition. Some cases are known to be associated with genetic mutations or serum auto-antibodies, but the exact mechanisms in most cases are unknown. Recently, osmotic factors have been suggested to trigger some neurological disorders, such as neuromyelitis optica. The aim of the present study was to assess the possible association of osmotic factors in the pathogenesis of distal polyneuropathy. We prospectively measured the serum levels of osmolality, electrolytes, total protein, albumin, blood urea nitrogen, glucose, and osmolality gap in the patients with acute distal polyneuropathy before treatments (n = 12) and those with other comprehensive neurological disorders such as multiple sclerosis and neurodegenerative diseases (n = 176). Then, we compared each osmotic fraction between the two groups. As a result, all of the 12 patients with acute distal polyneuropathy, including 4 patients with chronic inflammatory demyelinating polyneuropathy, showed abnormally high or low values of osmolality gap, compared to the others (p < 0.0001, F-test). In the patients with other diseases, there were 2 patients with abnormally high osmolality gap values, which were attributable to their hyperlipidemia or high titer of serum autoantibody unrelated to polyneuropathy. In conclusion, serum osmolality gap would be elevated or decreased in the acute phase of distal symmetric polyneuropathy. Osmotic imbalance between the serum and nerve cells, based on abnormal excess or deficit of some unidentified serum osmolytes, may be one of the mechanisms in symmetric polyneuropathy with unknown causes.