Aggressive Prostate Cancer Is Prevented in ERαKO Mice and Stimulated in ERβKO TRAMP Mice

Previous evidence suggests soy genistein may be protective against prostate cancer, but whether this protection involves an estrogen receptor (ER)-dependent mechanism is unknown. To test the hypothesis that phytoestrogens may act through ERα or ERβ to play a protective role against prostate cancer, we bred transgenic mice lacking functional ERα or ERβ with transgenic adenocarcinoma of mouse prostate (TRAMP) mice. Dietary genistein reduced the incidence of cancer in ER wild-type (WT)/transgenic adenocarcinoma of mouse prostate mice but not in ERα knockout (KO) or ERβKO mice. Cancer incidence was 70% in ERWT mice fed the control diet compared with 47% in ERWT mice fed low-dose genistein (300 mg/kg) and 32% on the high-dose genistein (750 mg/kg). Surprisingly, genistein only affected the well differentiated carcinoma (WDC) incidence but had no effect on poorly differentiated carcinoma (PDC). No dietary effects have been observed in either of the ERKO animals. We observed a very strong genotypic influence on PDC incidence, a protective effect in ERαKO (only 5% developed PDC), compared with 19% in the ERWT, and an increase in the incidence of PDC in ERβKO mice to 41%. Interestingly, immunohistochemical analysis showed ERα expression changing from nonnuclear in WDC to nuclear in PDC, with little change in ERβ location or expression. In conclusion, genistein is able to inhibit WDC in the presence of both ERs, but the effect of estrogen signaling on PDC is dominant over any dietary treatment, suggesting that improved differential targeting of ERα vs. ERβ would result in prevention of advanced prostate cancer.     

Peroxisome proliferator activating receptor alpha and gamma polymorphisms and metabolic abnormalities in HIV-infected patients receiving highly active antiretroviral therapy: the ANRS CO8 APROCO-COPILOTE study

Highly active antiretroviral therapy (HAART) is associated with fat redistribution and metabolic disorders. The present study was undertaken to evaluate the association between peroxisome proliferator activated receptor (PPAR)α and PPARγ polymorphisms, two genes involved in lipid metabolism and adipocyte differentiation, and elements of the metabolic syndrome, lipodystrophy, or carbohydrate metabolism abnormalities in patients receiving HAART. The frequency distribution of rare alleles for PPARα (L162V) and PPARγ (P12A and H449H) was compared using the chi square test in 363 HIV-1-infected patients classified according to the presence or absence of the metabolic syndrome after 48 months of follow-up on their first PI-containing regimen. The P12A rare g allele was present in 12% patients with normal glucose metabolism, 11% patients with impaired glucose tolerance or impaired fasting glucose, and 35% patients with diabetes (p=0.014). The rare g allele for L162V was present in 14% of patients free of hypertriglyceridemia and in 7% patients with hypertriglyceridemia (p=0.04). The rare g allele for L162V was found in 15% of patients free of any sign of lipodystrophy and 8% with at least one sign of lipodystrophy (p=0.04) and the rare t allele for H449H was found in 14% of patients free of any sign of lipodystrophy and 23% of patients with at least one sign of lipodystrophy (p=0.05). There was no convincing association between any polymorphism of PPARα and PPARγ and each individual component of the metabolic syndrome, except for the relationship of the P12A polymorphism with diabetes. Confirmatory studies on a larger number of individuals are needed.     

Altered lipid, apolipoprotein, and lipoprotein profiles in inflammatory bowel disease: consequences on the cholesterol efflux capacity of serum using Fu5AH cell system

Epidemiological data suggest a link between chronic inflammation condition and atherosclerosis. Infection and inflammation can also impair lipoprotein metabolism and produce a wide variety of changes in plasma concentrations of lipids and lipoproteins. Twenty-one patients with inflammatory bowel diseases (IBDs) and 28 healthy subjects were recruited. Serum concentrations of lipids, lipoproteins, apolipoproteins, leptin, ghrelin, and inflammation markers (C-reactive protein and serum amyloid A) were measured, and subjects' lipoproteins were characterized. The ability of patients with serum IBD to efflux free cell cholesterol was measured. Serum cholesterol, high-density lipoprotein cholesterol, apolipoprotein (apo) A-I, apoC-II, apoC-III bound to apoB, phospholipid, and phospholipids not bound to apoB levels were significantly lower, whereas serum triglyceride, serum amyloid A, and C-reactive protein levels were significantly higher in patients with active IBD. Apolipoprotein A-I immunoreactivity (pre-beta small particles and small alpha-high-density lipoprotein particles) is decreased in patients with IBD. In contrast, apoE immunoreactivity (slow/small apoE containing lipoprotein particles [LpE particle]) increased in these patients. The efflux capacity of serum from patients with IBD using [(3)H]-cholesterol-labeled Fu5AH cells was reduced (P < .005). Our results demonstrate that, in subjects with active IBD, inflammation leads to alterations in lipid, apolipoprotein, and lipoprotein profiles and reduced cholesterol efflux. These changes are similar to those proposed to promote atherogenesis and may contribute to the development of cardiovascular events.     

Pseudotumour cerebri occurring in association with the Chiari malformation.

Summary The case is described of a 12-year-old girl presenting with raised intracranial pressure without ventricular dilatation and a type 1 Chiari malformation. This was taken to be a coincidental association of pseudotumour cerebri and the Chiari malformation. Treatment of the pseudotumour with Diamox gave rapid and sustained relief of the intracranial hypertension without change in the Chiari malformation. In addition, a series of 156 cases of pseudotumour cerebri was reviewed for evidence of the Chiari malf ormation. An overall incidence of 1.3%, rising to 2.7% in patients with MR scanning [excluding the case described] was found.     

Anatomical distribution of vertebral fractures: comparison of pediatric and adult spines

Summary

We compared the distribution of vertebral fractures in adults and children and found that fractures occurred in different locations in the two age groups. This likely relates to the different shape of the immature spine.

Introduction

We hypothesized that the anatomical distribution of vertebral fractures (VF) would be different in children compared to adults.

Methods

We compared the distribution of VF defined using the Genant semi-quantitative method (GSQ method) in adults (N?=?221; 545 fractures) and in children early in the course of glucocorticoid therapy (N?=?44; 94 fractures).

Results

The average age in the adult cohort was 62.9?years (standard deviation (SD), 13.4?years), 26% was male, the mean lumbar spine Z-score was ?1.0 (SD, 1.5), and the corresponding T-score was ?2.4 (SD, 1.4). The pediatric cohort median age was 7.7?years (range, 2.1–16.6?years), the mean lumbar spine Z-score was ?1.7 (SD, 1.5), 52% was male, and disease categories were acute lymphoblastic leukemia (66%), rheumatological conditions (21%), and nephrotic syndrome (14%). The VF distribution was biphasic in both populations, but the peaks differed in location. In adults, the peaks were at T7/T8 and at T12/L1. In children, the focus was higher in the thoracic spine, at T6/T7, and lower in the lumbar spine, at L1/L2. When children were assessed in two age-defined sub-groups, a biphasic VF distribution was seen in both, but the upward shift of the thoracic focus to T6 was observed only in the older group, with the highest rates of fracture present between ages 7 and 10?years.

Conclusions

These results suggest that the anatomical distribution of VF differs between children and adults, perhaps relating to the different shape of the immature spine, notably the changing ratio of kyphosis to lordosis.     

Skeletal findings in children recently initiating glucocorticoids for the treatment of nephrotic syndrome

Summary

Eighty children with nephrotic syndrome underwent lumbar spine densitometry and vertebral morphometry soon after glucocorticoid initiation. We found an inverse relationship between glucocorticoid exposure and spine areal bone mineral density (BMD) Z-score and a low rate of vertebral deformities (8%).

Introduction

Vertebral fractures are an under-recognized complication of childhood glucocorticoid-treated illnesses. Our goal was to study the relationships among glucocorticoid exposure, lumbar spine areal BMD (LS BMD), and vertebral shape in glucocorticoid-treated children with new-onset nephrotic syndrome.

Methods

Lateral thoracolumbar spine radiography and LS BMD were performed in 80 children with nephrotic syndrome (median age 4.4?years; 46 boys) within the first 37?days of glucocorticoid therapy. Genant semiquantitative grading was used as the primary method for vertebral morphometry; the algorithm-based qualitative (ABQ) method was used for secondary vertebral deformity analysis.

Results

Six of the 78 children with usable radiographs (8%; 95% confidence interval 4 to 16%) manifested a single Genant grade 1 deformity each. All deformities were mild anterior wedging (two at each of T6, T7, and T8). Four of the 78 children (5%; 95% confidence interval 2 to 13%) showed one ABQ sign of fracture each (loss of endplate parallelism; two children at T6 and two at T8). Two of the children with ABQ signs also had a Genant grade 1 deformity in the same vertebral body. None of the children with a Genant or ABQ deformity reported back pain. An inverse relationship was identified between LS BMD Z-score and glucocorticoid exposure.

Conclusions

Although we identified an inverse relationship between steroid exposure and LS BMD soon after glucocorticoid initiation for childhood nephrotic syndrome, there was only a low rate of vertebral deformities. The clinical significance of these findings requires further study.     

The Ukraine–Russia War Is Deepening Food Insecurity,Unhealthy Dietary Patterns and the Lack of Dietary Diversity in Lebanon: Prevalence,Correlates and Findings from a National Cross-Sectional Study

Background: Due to Russia and Ukraine’s key roles in supplying cereals and oilseeds, the Russia–Ukraine war intensifies the current food availability and price challenges in Lebanon, which is a major wheat importer. Given these constraints, we conducted this study to assess the prevalence and correlates of food insecurity, low dietary diversity (DD), unhealthy dietary patterns, and the shifts in households’ food-related habits in response to the Russia–Ukraine war among a representative sample of Lebanese household’s members aged 18 years and above (N = 914). Methods: Data were collected between June and July 2022 using self-administered questionnaires; Results: Findings showed that nearly half of the households consume an undiversified diet (46%), and 55.3% ate fewer than two meals per day. The prevalence of food insecurity among Lebanese households was 74%, with one in every four households being severely food insecure. In addition, the majority of households’ members went out shopping and purchased food less than the pre-war period (68.7% and 70.3%, respectively). Furthermore, almost 68.3% of households’ members highlighted price increases for cereal products, which were the least available and most stocked items. Findings obtained through binary logistic regression also showed that food insecurity was two times higher among households with low monthly income, 35% higher among females, and three times higher among married participants; Conclusions: The impact of the Russia–Ukraine conflict on food security in Lebanon requires a systems-thinking approach as well as international effort to understand the challenges and find solutions to minimize the war’s negative effects.     

A facile synthesis of [(11)C]acetylene.

Acetylene is a versatile synthon organic chemistry. The complexity and difficulty of synthesis of [(11)C]acetylene has limited its use as a labeling intermediate for PET radiotracers. A new method for production of [(11)C]acetylene has been developed in our laboratory that simplifies the synthesis procedure allowing for easy automation and implementation. The technique is a modification of Madsen et al. (1981, Phys. Med. Biol. 26(5), 875) that utilized carbon dioxide ((11)C) and barium. First [(11/12)C]CO(2) was trapped at room temperature on barium within a quartz reaction tube, then heated to 900 degrees C under hydrogen flow to release [(11)C]acetylene. Hydrogen gas is apparently oxidized to form water vapor which reacts immediately with the formed carbide to liberate acetylene. Radiochemical yields of 31.4--75.4% and specific activities of 0.11-- 161 mCi/micromol have been obtained with radiochemical purities greater than 99%. This technique provides a new, efficient and very practical synthesis of [(11)C]acetylene that can be utilized as synthon for novel PET radiopharmaceuticals.     

Idiopathic macrocephaly in the infant: long-term neurological and neuropsychological outcome

RATIONALE: The long-term outcome of idiopathic macrocephaly is presently unknown. METHODS AND RESULTS: In the current study (n=15), MRI conducted at long-term review showed regression of orbito-frontal extradural collections and normal or slightly enlarged ventricular space compared to infant examination. Head circumference had normalised in all but one participant. Neuropsychological assessments of nine participants showed general intellectual ability within the normal range in the majority of participants; however, specific deficits in attention were evident. Clinical interviews conducted with a smaller sub-group revealed anecdotal histories of behavioural difficulties and reading or arithmetic difficulties in half of the total sample. CONCLUSIONS: Prospective review studies such as this indicate that abnormal radiological findings in infancy are not necessarily predictive of neurodevelopmental problems and may reflect a normal variant. However, while overall intellectual ability may be within average limits in this diagnostic sample, considerable individual variations remain in specific areas of neuropsychological function.     

Clinical experience with a single field rotational total skin electron irradiation technique for cutaneous T-cell lymphoma.

Between October 1981 and December 1989, 44 patients with cutaneous T-cell lymphoma (CTCL) were treated with a single field rotational total skin electron irradiation (RTSEI) technique developed in the McGill University, Department of Radiation Oncology. Only 11 (25%) of the 44 patients had received no prior treatment. Three-quarters (33/44) had advanced (T3 or T4) disease. Complete responses were seen in 32/44 (73%) of patients (91% T2, 71% T3 and 58% T4), but only 3/11 (27%) of patients with T2 disease and 3/21 (14%) of patients with T3 disease remain in continuous complete remission in the skin, after median intervals of 58 and 35 months, respectively. Median cause-specific survival for the whole group is 43 months and survival at 5 years is 38%. Survival was significantly better for patients with T2 disease than for patients with T3 disease (relative risk 4.3; 95% CI 1.4-13.2) and patients with T4 disease (relative risk 3.1; 95% CI 0.8-12.1). The RTSEI technique used at McGill has depth-dose characteristics and photon contamination similar to other commonly used TSEI techniques. It is relatively simple and provides a homogenous dose distribution over the entire skin surface in a short treatment time. Results of treatment are similar to those obtained with other techniques. For T2 disease, TSEI is an effective treatment modality with a possibility of long-term tumor control. For more advanced disease, more aggressive treatment, which may include TSEI, is necessary.