Dietary intake of phytoestrogens, estrogen receptor-beta polymorphisms and the risk of prostate cancer

BACKGROUND: The causes of prostate cancer are poorly understood, but genetic factors may be more important than for many other malignancies, and dietary phytoestrogens may be protective. Because phytoestrogens bind tightly to the estrogen receptor-beta, we conducted an epidemiologic investigation of synergistic effects between phytoestrogen intake and estrogen receptor-beta gene polymorphisms. METHODS: We performed a population-based case-control study in Sweden. All participants reported their phytoestrogen intake and donated a blood sample. We identified four haplotype-tagging single nucleotide polymorphisms (htSNPs) and genotyped these htSNPs in 1314 prostate cancer patients and 782 controls. Odds ratios were estimated by multivariate logistic regression. Interactions between phytoestrogen intake and estrogen receptor-beta SNPs on prostate cancer risk were evaluated considering both multiplicative and additive effect scales. RESULTS: We found a significant multiplicative interaction (P = 0.04) between dietary intake of phytoestrogens and a promoter SNP in the estrogen receptor-beta gene (rs 2987983-13950), but not with any of the three other htSNPs (P = 0.11, 0.69, 0.85). Among carriers of the variant promoter alleles, we found strong inverse associations with increasing intake of total phytoestrogens (odds ratio for highest vs. lowest quartile = 0.43; P for trend <0.001), isoflavonoids (odds ratio = 0.63; P for trend = 0.05), and coumestrol (odds ratio = 0.57; P for trend = 0.003). We found no association between phytoestrogens and prostate cancer among carriers homozygous for the wild-type allele (TT). CONCLUSIONS: Our study provides strong evidence that high intake of phytoestrogens substantially reduce prostate cancer risk among men with specific polymorphic variation in the promoter region of the estrogen receptor-beta gene.     

Nowcasting (Short-Term Forecasting) of COVID-19 Hospitalizations Using Syndromic Healthcare Data,Sweden, 2020

We report on local nowcasting (short-term forecasting) of coronavirus disease (COVID-19) hospitalizations based on syndromic (symptom) data recorded in regular healthcare routines in Östergötland County (population ≈465,000), Sweden, early in the pandemic, when broad laboratory testing was unavailable. Daily nowcasts were supplied to the local healthcare management based on analyses of the time lag between telenursing calls with the chief complaints (cough by adult or fever by adult) and COVID-19 hospitalization. The complaint cough by adult showed satisfactory performance (Pearson correlation coefficient r>0.80; mean absolute percentage error <20%) in nowcasting the incidence of daily COVID-19 hospitalizations 14 days in advance until the incidence decreased to <1.5/100,000 population, whereas the corresponding performance for fever by adult was unsatisfactory. Our results support local nowcasting of hospitalizations on the basis of symptom data recorded in routine healthcare during the initial stage of a pandemic.     

The Level of Anxiety and Pain Perception of Endodontic Patients

Objectives

to compare the level of anxiety reported by patients and assessed by dentists. Also, the expected and actual pain during the treatment perceived by the patient and dentist were assessed.

Methods

sixty six endodontic patients filled in two questionnaires, prior to and after the treatment, so did their therapists. The first set of questions for patients was regarding demographics, the frequency of dental visits, the level of anxiety and expectations about the level of pain. Before the treatment, dentists estimated the level of patients'' anxiety and the expected intensity of pain. After the treatment, the patients evaluated the level of experienced pain and dentists'' empathy during the treatment, while dentists reassessed the intensity of patients'' pain.The data were statistically analysed by t-test for paired samples and by Spearmans''s Rho correlation coefficient at level of significance set at 0.05.

Results

Patients'' expectation of pain intensity was higher than the actual pain during the treatment (t-test=3.540, p=0.001). There was no difference in the level of pain which dentists expected and their perception of pain during the procedure. There was a statistically significant correlation between the patients'' level of anxiety and recognition of it by dentists (Spearman Rho=0.460, p<0.001). A higher level of anxiety increased the expected intensity of pain (Spearman Rho=0.401, p=0.001). Actual intensity of pain was not significantly associated with dental anxiety (Spearman Rho=0.080, p=0.524).

Conclusion

Since the level of dental anxiety was associated with the increased intensity of expected pain, a vicious cycle of pain and anxiety may be terminated by giving positive information to the patient before and during endodontic procedures.     

Extreme sarcoplasmic reticulum volume loss and compensatory T-tubule remodeling after Serca2 knockout

Cardiomyocyte contraction and relaxation are controlled by Ca(2+) handling, which can be regulated to meet demand. Indeed, major reduction in sarcoplasmic reticulum (SR) function in mice with Serca2 knockout (KO) is compensated by enhanced plasmalemmal Ca(2+) fluxes. Here we investigate whether altered Ca(2+) fluxes are facilitated by reorganization of cardiomyocyte ultrastructure. Hearts were fixed for electron microscopy and enzymatically dissociated for confocal microscopy and electrophysiology. SR relative surface area and volume densities were reduced by 63% and 76%, indicating marked loss and collapse of the free SR in KO. Although overall cardiomyocyte dimensions were unaltered, total surface area was increased. This resulted from increased T-tubule density, as revealed by confocal images. Fourier analysis indicated a maintained organization of transverse T-tubules but an increased presence of longitudinal T-tubules. This demonstrates a remarkable plasticity of the tubular system in the adult myocardium. Immunocytochemical data showed that the newly grown longitudinal T-tubules contained Na(+)/Ca(2+)-exchanger proximal to ryanodine receptors in the SR but did not contain Ca(2+)-channels. Ca(2+) measurements demonstrated a switch from SR-driven to Ca(2+) influx-driven Ca(2+) transients in KO. Still, SR Ca(2+) release constituted 20% of the Ca(2+) transient in KO. Mathematical modeling suggested that Ca(2+) influx via Na(+)/Ca(2+)-exchange in longitudinal T-tubules triggers release from apposing ryanodine receptors in KO, partially compensating for reduced SERCA by allowing for local Ca(2+) release near the myofilaments. T-tubule proliferation occurs without loss of the original ordered transverse orientation and thus constitutes the basis for compensation of the declining SR function without structural disarrangement.