Childhood Cancer and the Risk of ESKD

BackgroundIncreasing cancer incidence among children alongside improved treatments has resulted in a growing number of pediatric cancer survivors. Despite childhood cancer survivors’ exposure to various factors that compromise kidney function, few studies have investigated the association between childhood cancer and future kidney disease.MethodsTo assess the risk of ESKD among childhood cancer survivors, we conducted a nationwide, population-based, retrospective cohort study that encompassed all Israeli adolescents evaluated for mandatory military service from 1967 to 1997. After obtaining detailed histories, we divided the cohort into three groups: participants without a history of tumors, those with a history of a benign tumor (nonmalignant tumor with functional impairment), and those with a history of malignancy (excluding kidney cancer). This database was linked to the Israeli ESKD registry to identify incident ESKD cases. We used Cox proportional hazards models to estimate the hazard ratio (HR) of ESKD.ResultsOf the 1,468,600 participants in the cohort, 1,444,345 had no history of tumors, 23,282 had a history of a benign tumor, and 973 had a history of malignancy. During a mean follow-up of 30.3 years, 2416 (0.2%) participants without a history of tumors developed ESKD. Although a history of benign tumors was not associated with an increased ESKD risk, participants with a history of malignancy exhibited a substantially elevated risk for ESKD compared with participants lacking a history of tumors, after controlling for age, sex, enrollment period, and paternal origin (adjusted HR, 3.2; 95% confidence interval, 1.3 to 7.7).ConclusionsChildhood cancer is associated with an increased risk for ESKD, suggesting the need for tighter and longer nephrological follow-up.     

The effect of increasing sets (within one treatment session) and different set durations (between treatment sessions) of lumbar spine posteroanterior mobilisations on pressure pain thresholds

Spinal mobilisations are a common form of treatment intervention applied by physiotherapists in clinical practice to manage musculoskeletal pain and/or dysfunction. Previous research has demonstrated that mobilisations cause a hypoalgesic effect. However, there is very little research investigating the optimal treatment dose inducing this effect.AimTo investigate the effect of the number of sets (up to 5) and different durations (30 vs. 60 s) on pressure pain thresholds (PPTs) at different sites.MethodsThis single-blinded, randomised, same subject repeated measures crossover design included 19 asymptomatic healthy volunteers. The participants received 5 sets of either 30 or 60 s of postero-anterior mobilisations to L4 on different days. PPTs were measured immediately before, between and after the intervention at 4 different standardised sites.ResultsA 4-way ANOVA analysis revealed that there was no statistically significant difference between 30 versus 60 s of mobilisations. However, there was a tendency for PPT values to be higher for the 60 s intervention. All PPT measurements after the interventions were significantly higher than the baseline. Only the measurement after the 4th set of mobilisations was significantly higher than the measurement after the 1st set (p = 0.035).ConclusionsThe results suggest that in order to induce the greatest local hypoalgesia, at least 4 sets of mobilisations are required. The different durations of 30 versus 60 s of mobilisation may not change the extent of the hypoalgesic effect.     

Routine screening mammography in women older than 74 years: a review of the available data

OBJECTIVE: The efficacy of population screening mammography for the age group of 50-74 years has been demonstrated. However, only limited data are available regarding women aged 75 and over, and recommendations for breast cancer screening in this age group vary in different countries. The aim of the current study is to review the evidence of the efficacy of breast cancer screening in women over the age of 74 years. METHODS: Studies published in English were retrieved by systematically searching MEDLINE (for papers published until August 2006), and by manually examining the references of the original articles and reviews retrieved. All studies that dealt with screening mammography over age 74 years were included. The studies were reviewed according to their outcomes and study design, focusing on breast cancer mortality and stage of breast cancer at diagnosis. RESULTS: Three studies focused on the relationship between breast cancer screening and mortality; in the 75-84 years age group, the risk of disease-specific mortality was approximately two-fold higher among women who did not perform screening mammography compared to women who did. Another four studies showed that women who underwent screening mammography had significantly smaller tumors and earlier disease stage at diagnosis. CONCLUSIONS: Regular mammography screening in older women may be associated with an earlier-stage disease and lower breast cancer mortality. These data support the use of screening mammography above age 75 years based on individual evaluations, rather than setting an upper age limit for breast cancer screening.     

Induction of rainbow trout MH class I and accessory proteins by viral haemorrhagic septicaemia virus

Major histocompatibility (MH) class I receptors are glycoproteins which play a critical role during responses to intracellular pathogens by presenting endogenous peptides to cytotoxic T cell lymphocytes (CD8+). To date, little is known about MH class I regulation at the protein level during viral infections in fish. In this study, we characterised the MH class I pathway response to polyinosinic–polycytidylic acid (poly I:C) and upon infection with viral haemorrhagic septicemia virus (VHSV) genotype IVa using the rainbow trout monocyte/macrophage cell line RTS11. A 14-day challenge with VHSV IVa at 14 °C demonstrated enhanced expression of the class I heavy chain, β2 microglobulin (β2M) and tapasin, while the expression of other accessory molecules ERp57 and calreticulin remained unchanged. However, when infection occurred at 2 °C no change in expression levels of any of these molecules was observed. β2M accumulated in the media of RTS11 over time, however the β2M concentrations were 2 fold higher in cultures infected with VHSV 14 days post infection. Strikingly, when cells were maintained at 2 °C the secretion of β2M was significantly reduced in both infected and non-infected cultures. These results indicate that VHSV infection alters the kinetics of β2M release as well as the expression of MH class I and suggests that cellular immunity against VHSV can be compromised at low temperatures which may increase host susceptibility to this virus during the winter.     

Collective cell migration of the nephric duct requires FGF signaling

Background : During the course of development, the vertebrate nephric duct (ND) extends and migrates from the place of its initial formation, adjacent to the anterior somites, until it inserts into the bladder or cloaca in the posterior region of the embryo. The molecular mechanisms that guide ND migration are poorly understood. Results : A novel Gata3‐enhancer‐Gfp‐based chick embryo live imaging system was developed that permits documentation of ND migration at the individual cell level for the first time. FGF Receptors and FGF response genes are expressed in the ND, and FGF ligands are expressed in surrounding tissues. FGF receptor inhibition blocked nephric duct migration. Individual inhibitors of the Erk, p38, or Jnk pathways did not affect duct migration, but inhibition of all three pathways together did inhibit migration of the duct. A localized source of FGF8 placed adjacent to the nephric duct did not affect the duct migration path. Conclusions : FGF signaling acts as a “motor” that is required for duct migration, but other signals are needed to determine the directionality of the duct migration pathway. Developmental Dynamics 244:157–167, 2015. © 2014 Wiley Periodicals, Inc.     

Cancer incidence in persons with Down syndrome in Israel

The purpose of this study was to assess the incidence rates of leukaemia and other malignancies in persons with Down syndrome in Israel. The target population consisted of all persons with Down syndrome in the period of 1948-1995 and the study population was divided into two subgroups: (1) Persons born in Israel between 1979-95 (registry group) and (2) Persons currently or past-institutionalised, born before 1979 (institution group). The study population was linked to the Cancer Registry and cases that had been diagnosed through December 1995 were subsequently identified. The observed incidence rates were compared to expected rates in the general population. Standardised Incidence Ratios (SIR) and 95% confidence intervals were computed for each disease category. Analyses of results were performed separately for each subgroup of our study population. In the registry group seven cancer cases were observed as compared to 1.5 expected (SIR = 4.67 95% CI 1.9-9.6), all of which were leukaemia cases. For the institution group a total of 17 cancer cases were observed compared to 12.8 expected. These included four cases of leukaemia (SIR = 6.90 95% CI 1.9-17.7). An excess of gastric cancer in males, based on two cases (SIR = 11.9 95% CI 1.3-42.9) was also observed. The significant excess of leukaemia in the Down syndrome population in Israel is in accordance with other international studies. The excess of gastric cancer in males with Down syndrome, which has not been reported before, should be further explored.     

Interregional synaptic competition in neurons with multiple STDP-inducing signals

Neocortical layer 5 (L5) pyramidal cells have at least two spike initiation zones: Na(+) spikes are generated near the soma, and Ca(2+) spikes at the apical dendritic tuft. These spikes interact with each other and serve as signals for synaptic plasticity. The present computational study explores the implications of having two spike-timing-dependent plasticity (STDP) signals in a neuron, each with its respective regional population of synaptic "pupils." In a detailed model of an L5 pyramidal neuron, competition emerges between synapses belonging to different regions, on top of the competition among synapses within each region, which characterizes the STDP mechanism. Interregional competition results in strengthening of one group of synapses, which ultimately dominates cell firing, at the expense of weakening synapses in other regions. This novel type of competition is inherent to dendrites with multiple regional signals for Hebbian plasticity. Surprisingly, such interregional competition exists even in a simplified model of two identical coupled compartments. We find that in a model of an L5 pyramidal cell, the different synaptic subpopulations "live in peace" when the induction of Ca(2+) spikes requires the back-propagating action potential (BPAP). Thus we suggest a new key role for the BPAP, to maintain the balance between synaptic efficacies throughout the dendritic tree, thereby sustaining the functional integrity of the entire neuron.     

硒化不饱和脂酸及相应脂酸对人肝癌细胞株DNA合成的抑制作用

本实验以~3H-TdR(~3H-胸腺嘧啶核苷)掺入法研究了相同碳链长度的硒化不饱和脂酸及相应未硒化脂酸对7402人肝癌细胞株DNA合成的抑制作用。实验证明,终浓度为150ug/ml的受试物对人肝癌细胞株DNA合成的抑制作用以硒化亚麻酸量强,与硒化亚油酸、硒化油酸和油酸相比,差异非常显著(P<0.01),与亚油酸相比,差异显著(P<0.05),但与亚麻酸相比,差异未达统计学的显著程度(P>0.05),硒化亚油酸与亚油酸之间无差异(P>0.05),而硒化油酸与油酸则差异非常显著(P<0.01)。表明:含2-3个双键的脂酸,硒化与否,抑制癌细胞DNA合成强度差异不大,但对仅含一个双键者,硒化可显著增强对DNA合成的抑制作用。各种受试物对人肝癌细胞株的杀伤作用也以硒化亚麻酸最强。     

Gender effect on vascular responsiveness after bariatric surgery

Obesity, particularly abdominal obesity, is associated with increased risks of arterial hypertension, diabetes mellitus, hyperlipidemia, sleep apnea, coronary artery disease, stroke and mortality. Weight loss surgery is the most effective treatment for morbid obesity, mainly because medical and dietary treatments have been proven insufficient in the long run. Our primary end point was to study the gender effect on vascular responsiveness (endothelial function and the ankle brachial index [ABI]) 3 months post bariatric surgery. Our secondary end points were to study the effect of gender on antropometric parameters (BMI, waist circumference) and chronic diseases (diabetes mellitus type II, arterial hypertension) 3 months following bariatric surgery, and to find independent variables that may affect and predict the post-operative clinical outcome. Methods: In this prospective study, patients were evaluated one day before surgery and 3 months afterwards. Ankle brachial index was measured while the patient was supine after 15 minutes rest and measurement of the systolic blood pressure in all four extremities was done. The brachial artery method was used to measure endothelial function expressed as flow mediated diameter percent change (FMD %). FMD% more than 10% is considered a normal response. Results: Compared with diabetic females, diabetic males had a higher postoperative BMI (men with diabetes mellitus did not lose weight as much as diabetic women) (β=-0.299; P=0.04), while women with diabetes mellitus had a more significant reduction in BMI postoperatively (β=+0.287; P=0.04). Following bariatric surgery, 12 of the 21 patients with diabetes mellitus type II did not need any medications for diabetes (kept HbA1c% less than 6.5%). All other diabetic patients improved their diabetes mellitus status. Women significantly improved their ABI (average increase of 0.07, p=0.04) and their endothelial function (FMD% change was improved from -3.5±9.0% to 14.8±8.1%, an improvement of 18.3%, p<0.001). Systolic blood pressure was decreased significantly (by 6.6 mmHg, p=0.04). Men improved their endothelial function (FMD% change was improved from -1.3±10.1% to 11.7±6.2%, p<0.001), but no significant change was observed in systolic blood pressure (p=0.29) nor in ABI (P=0.8). A linear regression analysis found that a higher baseline FMD% significantly predicted a higher postoperative FMD% (β=0.294, P=0.03). In obese males, the higher the baseline BMI the worse the post operative endothelial function (β=-0.921, Pd<0.001) and the same adverse effect was documented for hypertensive men (β=-0.380, P=0.05). For females, the higher the baseline FMD% the higher the postoperative FMD% (β=+0.397; P=0.01) [a favorable outcome]. Discussion: Our study has demonstrated a possible mechanistic insight into gender effects observed in epidemiological studies through improvement in vascular response in females undergoing this operation including a better reduction in systolic blood pressure and a better weight reduction in diabetic women with improvement in ABI; unlike males, who did not improve their ABI and did not decrease systolic blood pressure, and the finding that obese diabetic males and obese hypertensive males did the worst.