Saethre‐Chotzen syndrome: Notable intrafamilial phenotypic variability in a large family with Q28X TWIST mutation

Saethre‐Chotzen syndrome is an autosomal dominant disease characterized by craniosynostosis, ptosis, and limb and external ear abnormalities. Variable expressivity is a well‐known phenomenon in this disorder. A large Indian family has been recently identified as carrying a nonsense TWIST mutation (Q28 X) in 17 members, of whom 16 were examined in detail. Only 4 (25%) of the patients showed patent craniostenosis, namely, oxycephaly. The penetrance of craniosynostosis in this family is lower than previously reported in the literature. Fifteen patients (93%) had moderate to severe ptosis. Minor limb and external ear abnormalities were present in most patients. Eyelid features were the hallmark of the disease for 12 members of the family, suggesting that mutations in TWIST may lead to a phenotype with mainly palpebral features and no craniostenosis. The clinical analysis of this large family clearly illustrates the significant variable expressivity, probably related to haploinsufficiency because of the TWIST mutation. This phenotypic variability remains unclear but could be the result of modifier genes and/or genetic background effect, as noticed previously in the transgenic twist‐null heterozygous mice. © 2002 Wiley‐Liss, Inc.     

Evolution of sleep and sleep EEG after hemispheric stroke

The evolution of subjective sleep and sleep electroencephalogram (EEG) after hemispheric stroke have been rarely studied and the relationship of sleep variables to stroke outcome is essentially unknown. We studied 27 patients with first hemispheric ischaemic stroke and no sleep apnoea in the acute (1-8 days), subacute (9-35 days), and chronic phase (5-24 months) after stroke. Clinical assessment included estimated sleep time per 24 h (EST) and Epworth sleepiness score (ESS) before stroke, as well as EST, ESS and clinical outcome after stroke. Sleep EEG data from stroke patients were compared with data from 11 hospitalized controls and published norms. Changes in EST (>2 h, 38% of patients) and ESS (>3 points, 26%) were frequent but correlated poorly with sleep EEG changes. In the chronic phase no significant differences in sleep EEG between controls and patients were found. High sleep efficiency and low wakefulness after sleep onset in the acute phase were associated with a good long-term outcome. These two sleep EEG variables improved significantly from the acute to the subacute and chronic phase. In conclusion, hemispheric strokes can cause insomnia, hypersomnia or changes in sleep needs but only rarely persisting sleep EEG abnormalities. High sleep EEG continuity in the acute phase of stroke heralds a good clinical outcome.     

Genomic instability occurs in colorectal carcinomas but not in adenomas

Genomic instability, as demonstrated by the presence of additional alleles at short tandemly repeated (STR) loci, has recently been observed in colorectal tumours from individuals with hereditary non-polyposis colorectal cancer (HNPCC), and in some sporadic tumours. These neoplasms have been called replication error positive (RER⁺). In this study, we confirm the presence of genomic instability in a proportion of unselected colorectal carcinomas but find no evidence of instability in adenomas. We further report replication errors in a tetranucleotide sequence, and in STRs within two tumour suppressor genes. 108 colorectal adenocarcinomas and 46 adenomas were analysed for the presence of variant bands at 4–15 microsatellite markers. Seven (6.5%) of carcinomas were RER⁺, four of which originated from the proximal colon. Analysis of the adenomas and of matched adenoma-carcinoma and carcinoma-metastatic samples from four patients suggests that the replication errors may occur during the development of carcinomas but are rare in adenomas. © 1993 Wiley-Liss, Inc.     

The t(II; 22)(pI5.5; qII.23) in a retroperitoneal rhabdoid tumor also includes a regional deletion distal to CRYBB2 on 22q

Translocations and deletions involving chromosomal band 22q 11 are common genetic aberrations in malignant rhabdoid tumors. Previous molecular analyses of a t(11; 22) in the malignant rhabdoid tumor cell line TM87-16 localized the breakpoint distal to BCR on 22q 11. In the present report, we have further refined the map position of this breakpoint between CRYBB2 and D22S258. Moreover, the D22S258, CRYBA4, D22S300, D22SI, and D22S310 loci, which lie between CRYBB2 and D22S42, were found to be deleted, presumably as a result of the translocation event. The identification of this deletion of at least 2 Mb on the long arm of chromosome 22 should be helpful for mapping the gene(s) in the region involved in the development of malignant rhabdoid tumors as well as providing insights into the mechanisms of chromosomal translocation in human solid tumors.     

Correction to: Neurocognitive functioning and health‑related quality of life of children after pediatric intensive care admission: a systematic review

Quality of Life Research -     

Fish Hydrolysate Supplementation Containing n-3 Long Chain Polyunsaturated Fatty Acids and Peptides Prevents LPS-Induced Neuroinflammation

Neuroinflammation constitutes a normal part of the brain immune response orchestrated by microglial cells. However, a sustained and uncontrolled production of proinflammatory factors together with microglial activation contribute to the onset of a chronic low-grade inflammation, leading to neuronal damage and cognitive as well as behavioral impairments. Hence, limiting brain inflammatory response and improving the resolution of inflammation could be particularly of interest to prevent these alterations. Dietary n-3 long chain polyunsaturated fatty acids (LC-PUFAs) and low molecular weight peptides are good candidates because of their immunomodulatory and proresolutive properties. These compounds are present in a fish hydrolysate derived from marine-derived byproducts. In this study, we compared the effect of an 18-day supplementation with this fish hydrolysate to a supplementation with docosahexaenoic acid (DHA) on lipopolysaccharide (LPS)-induced inflammation in mice. In response to peripherally injected LPS, the fish hydrolysate supplementation decreased the hippocampal mRNA expression of the proinflammatory cytokines IL-6 (p < 0.001), IL-1β (p = 0.0008) and TNF-α (p < 0.0001), whereas the DHA supplementation reduced only the expression of IL-6 (p = 0.004). This decline in proinflammatory cytokine expressions was associated with an increase in the protein expression of IκB (p = 0.014 and p = 0.0054 as compared to the DHA supplementation and control groups, respectively) and to a modulation of microglial activation markers in the hippocampus. The beneficial effects of the fish hydrolysate could be due in part to the switch of the hippocampal oxylipin profile towards a more anti-inflammatory profile as compared to the DHA supplementation. Thus, the valorization of fish byproducts seems very attractive to prevent and counteract neuroinflammation.     

The Design and Development of a Food Composition Database for an Electronic Tool to Assess Food Intake in New Caledonian Families

The food environment in New Caledonia is undergoing a transition, with movement away from traditional diets towards processed and discretionary foods and beverages. This study aimed to develop an up-to-date food composition database that could be used to analyze food and nutritional intake data of New Caledonian children and adults. Development of this database occurred in three phases: Phase 1, updating and expanding the number of food items to represent current food supply; Phase 2, refining the database items and naming and assigning portion size images for food items; Phase 3, ensuring comprehensive nutrient values for all foods, including saturated fat and total sugar. The final New Caledonian database comprised a total of 972 food items, with 40 associated food categories and 25 nutrient values and 615 items with portion size images. To improve the searchability of the database, the names of 593 food items were shortened and synonyms or alternate spelling were included for 462 foods. Once integrated into a mobile app-based multiple-pass 24-h recall tool, named iRecall.24, this country-specific food composition database would support the assessment of food and nutritional intakes of families in New Caledonia, in a cross-sectional and longitudinal manner, and with translational opportunities for use across the wider Pacific region.     

Contraceptive Method Uptake at Title X Health Centers in Utah

BackgroundThe Title X family planning program previously supported contraception for Utah clients with low incomes, yet its contributions may not have been sufficient to allow clients to select their preferred methods, including long-acting reversible contraceptives (LARCs). In this study, we compare the contraceptive method choices of self-paying clients with low incomes at three participating Title X health centers in Salt Lake County, Utah, before and after the removal of additional cost barriers.MethodsWe used retrospective medical record review to assess clients’ contraceptive choices during two 6-month periods: a control period with Title X-assisted sliding scale payment schedules (n = 2,776) and an intervention period offering no-cost contraceptive care (n = 2,065). We used logistic regression to identify the likelihood of selecting a LARC during the intervention period and multinomial regression to identify the selection probability of different types of available LARCs.ResultsDuring the control period, 16% of participants chose a LARC compared with 26% in the intervention period (p ≤ .001). During the intervention period, participants were 1.8 times more likely to select LARCs (95% confidence interval, 1.65–2.13) compared with non-LARC methods, holding covariates constant. In the multinomial regression, participants were three times more likely during the intervention period to select an implant than a pill, patch, or ring, holding all other covariates constant (odds ratio, 3.08; 95% confidence interval, 2.47–3.83).ConclusionsTitle X clients offered contraceptive methods without cost more frequently selected a LARC method. Title X funding reductions may impede individuals’ access to their contraceptive methods of choice.     

Positive microscopic surgical margins: Is there an association with survival in resected small gastrointestinal stromal tumors?

BackgroundFew studies evaluate the relationships between surgical approach, histologic margin, and overall survival in gastrointestinal stromal tumor. We test the hypothesis that margin positive resection is associated with compromised overall survival.MethodsWe queried the National Cancer Data Base to identify patients undergoing resections for gastrointestinal stromal tumors ≤3 cm in size between 2010 and 2015. Multivariable logistic regression was used to identify factors associated with positive microscopic margins on final pathology. Cox proportional hazard methods were used to evaluate factors associated with overall survival.Results2064 patients met inclusion criteria; 135 (6.5%) had a microscopically positive surgical margin. On multivariable regression, minimally invasive approach was not associated with risk of a positive margin (OR 1.06 95% CI [0.71, 1.59]). On Cox analysis, positive margin status was not associated with OS (R1: 1.03, CI [0.46–2.31], reference R0).ConclusionsPositive microscopic surgical margins are not associated with compromised overall survival in patients undergoing resection of small gastrointestinal stromal tumors. Minimally invasive surgical approaches do not compromise oncologic outcomes in these cases.     

The importance of the margin of resection and external radiation in non-lipomatous retroperitoneal sarcoma

BackgroundPrior studies evaluating the impact of adjuvant or neoadjuvant radiation on clinical outcomes of patients with non-lipomatous retroperitoneal sarcoma have been underpowered.MethodsWe queried the National Cancer Database to identify patients undergoing surgical resection of retroperitoneal sarcoma with non-lipomatous histology from 2004 to 2016. Multivariable logistic regression and Cox proportional hazards modelling with patients stratified by tumor size were used to identify factors associated with overall survival.Results3,394 patients met inclusion criteria. 592 had small (<5 cm), 1,186 had intermediate (5–10 cm), and 1,616 had large (>10 cm) tumors. Use of either neoadjuvant or adjuvant radiotherapy was associated with improved survival for patients with intermediate (neoadjuvant HR 0.67, CI [0.46, 0.98]; adjuvant HR 0.61, CI [0.50, 0.76]) and large (neoadjuvant HR 0.50, CI [0.37, 0.68]; adjuvant HR 0.56, CI [0.47, 0.69]) tumors, while adjuvant radiation therapy was associated with a survival benefit for small-sized tumors (HR 0.67, CI [0.46, 0.99]).ConclusionsRadiation therapy is associated with an overall survival benefit in patients presenting undergoing resection of non-lipomatous retroperitoneal sarcoma.