Severe maternal morbidity in Scotland.

Using a cohort study design, we analysed 17 diagnoses and 9 interventions (including critical care admission) as a composite measure of severe maternal morbidity for pregnancies recorded over 14 years in Scotland. There were 762,918 pregnancies, of which 7947 (10 in 1000 pregnancies) recorded 9345 severe maternal morbidity events, 2802 episodes of puerperal sepsis being the most common (30%). Severe maternal morbidity incidence increased from 9 in 1000 pregnancies in 2012 to 17 in 1000 pregnancies in 2018, due in part to puerperal sepsis recording. The odds ratio (95%CI) for severe maternal morbidity was higher for: older women, for instance 1.22 (1.13-1.33) for women aged 35-39 years and 1.44 (1.27-1.63) for women aged > 40 years compared with those aged 25-29 years; obese women, for instance 1.13 (1.06-1.21) for BMI 30-40 kg.m-2 and 1.32 (1.15-1.51) for BMI > 40 kg.m-2 compared with BMI 18.5-24.9 kg.m-2 ; multiple pregnancy, 2.39 (2.09-2.74); and previous caesarean delivery, 1.52 (1.40-1.65). The median (IQR [range]) hospital stay was 3 (2-5 [1-8]) days with severe maternal morbidity and 2 (1-3 [1-5]) days without. Forty-one women died during pregnancy or up to 42 days after delivery, representing mortality rates per 100,000 pregnancies of about 365 with severe maternal morbidity and 1.6 without. There were 1449 women admitted to critical care, 807 (58%) for mechanical ventilation or support of at least two organs. We recorded an incidence of severe maternal morbidity higher than previously published, possibly because sepsis was coded inaccurately in our databases. Further research may determine the value of this composite measure of severe maternal morbidity.

TGF-ß1 alters esophageal epithelial barrier function by attenuation of claudin-7 in eosinophilic esophagitis.

Barrier dysfunction has been implicated in the pathophysiology of eosinophilic esophagitis (EoE). Transforming growth factor-ß1 (TGF-ß1), a potent pleiotropic molecule, is increased in EoE; however, no study has evaluated its influence on esophageal epithelial barrier. We hypothesized that TGF-ß1 regulates barrier dysfunction in EoE. We aimed to determine the role of TGF-ß1 in the epithelial barrier in models of EoE. To examine the impact of TGF-ß1 on esophageal barrier, immortalized human esophageal epithelial (EPC2-hTERT) cells were exposed to TGF-ß1 during the three-dimensional air-liquid interface (3D-ALI) model in vitro. TGF-ß1 exposure diminished EPC2-hTERT barrier function as measured by transepithelial electrical resistance (TEER) and 3 kDa Fluorescein isothiocyanate dextran paracellular flux (FITC Flux), and hematoxylin and eosin (H&E) assessment revealed prominent cellular separation. In analysis of epithelial barrier molecules, TGF-ß1 led to the specific reduction in expression of the tight-junction molecule, claudin-7 (CLDN7), and this was prevented by TGF-ß-receptor I inhibitor. Short hairpin ribonucleic acid (shRNA)-mediated CLDN7 knockdown diminished epithelial barrier function, whereas CLDN7 overexpression resulted in protection from TGF-ß1-mediated barrier dysfunction. In pediatric EoE biopsies CLDN7 expression was decreased and altered localization was observed with immunofluorescence analysis, and the TGF-ß1 downstream transcription factor, phosphorylated SMAD2/3 (pSMAD2/3), was increased. Our data suggest that TGF-ß1 participates in esophageal epithelial barrier dysfunction through CLDN7 dysregulation.

Targeting granulocyte-macrophage colony-stimulating factor in epithelial and vascular remodeling in experimental eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic antigen-mediated clinicopathologic disease of the esophagus characterized by an eosinophil-predominant inflammatory infiltrate. A clinical hallmark is extensive tissue remodeling including basal zone hyperplasia, fibrosis, and angiogenesis. However, the cellular mechanisms responsible for these processes are not fully defined. We hypothesized that targeting granulocyte-macrophage colony-stimulating factor (GM-CSF; an agonist cytokine linked with eosinophil survival and activation) would be protective in a preclinical model of EoE. METHODS: Eosinophilic esophagitis-like esophageal inflammation was induced in the L2-IL5OXA EoE mouse model, and GM-CSF production was assessed by mRNA and protein analyses. Granulocyte-macrophage colony-stimulating factor-receptor-alpha expression patterns were examined by flow cytometric and immunofluorescence analysis. L2-IL5OXA EoE mice were treated with anti-GM-CSF neutralizing antibody or isotype control and assessed for histopathological indices of eosinophilia, epithelial hyperplasia, and angiogenesis by immunohistochemistry and RT-PCR. RESULTS: Significantly increased levels of esophageal GM-CSF expression was detected in the L2-IL5OXA mouse EoE model during active inflammation. Granulocyte-macrophage colony-stimulating factor-receptor-alpha was predominantly expressed on esophageal eosinophils during EoE, in addition to select cells within the lamina propria. Anti-GM-CSF neutralization in L2-IL5OXA EoE mice resulted in a significant diminution of epithelial eosinophilia in addition to basal cell hyperplasia and vascular remodeling. This treatment response was independent of effects on esophageal eosinophil maturation or activation. CONCLUSION: Granulocyte-macrophage colony-stimulating factor is a potential therapeutic target to reduce esophageal eosinophilia and remodeling.

Academic abilities and glycaemic control in children and young people with Type 1 diabetes mellitus.

AIMS: To determine if children and young people aged < 23 years with Type 1 diabetes differ in academic ability from age-matched control subjects without Type 1 diabetes and whether academic scores are related to glycaemic control. METHODS: Using a cross-sectional study design, we administered cognitive and academic tests (Woodcock-Johnson III Spatial Relations, General Information, Letter-Word Recognition, Calculation and Spelling tests) to young people with Type 1 diabetes (n=61) and control subjects (n=26) aged 9-22 years. The groups did not differ in age or gender. Participants with Type 1 diabetes had a disease duration of 5-17.7 years. History of glycaemic control (HbA1c , diabetic ketoacidosis and severe hypoglycaemic episodes) was obtained via medical records and interviews. RESULTS: The participants with Type 1 diabetes had a lower mean estimated verbal intelligence (IQ) level compared with those in the control group (P=0.04). Greater exposure to hyperglycaemia over time was associated with lower spelling abilities within the group with Type 1 diabetes (P=0.048), even after controlling for age, gender, socio-economic status, blood glucose level at time of testing and verbal IQ (P=0.01). History of severe hypoglycaemia or ketoacidosis was not associated with differences in academic abilities. CONCLUSIONS: In children and young people, Type 1 diabetes was associated with a lower verbal IQ. Moreover, increased exposure to hyperglycaemia was associated with lower spelling performance. These results imply that hyperglycaemia can affect cognitive function and/or learning processes that may affect academic achievement.

Epithelial-specific A2B adenosine receptor signaling protects the colonic epithelial barrier during acute colitis.

Central to inflammatory bowel disease (IBD) pathogenesis is loss of mucosal barrier function. Emerging evidence implicates extracellular adenosine signaling in attenuating mucosal inflammation. We hypothesized that adenosine-mediated protection from intestinal barrier dysfunction involves tissue-specific signaling through the A2B adenosine receptor (Adora2b) at the intestinal mucosal surface. To address this hypothesis, we combined pharmacologic studies and studies in mice with global or tissue-specific deletion of the Adora2b receptor. Adora2b(-/-) mice experienced a significantly heightened severity of colitis, associated with a more acute onset of disease and loss of intestinal epithelial barrier function. Comparison of mice with Adora2b deletion on vascular endothelial cells (Adora2b(fl/fl)VeCadCre(+)) or intestinal epithelia (Adora2b(fl/fl)VillinCre(+)) revealed a selective role for epithelial Adora2b signaling in attenuating colonic inflammation. In vitro studies with Adora2b knockdown in intestinal epithelial cultures or pharmacologic studies highlighted Adora2b-driven phosphorylation of vasodilator-stimulated phosphoprotein (VASP) as a specific barrier repair response. Similarly, in vivo studies in genetic mouse models or treatment studies with an Adora2b agonist (BAY 60-6583) recapitulate these findings. Taken together, our results suggest that intestinal epithelial Adora2b signaling provides protection during intestinal inflammation via enhancing mucosal barrier responses.

Intervening to alleviate word-finding difficulties in children: case series data and a computational modelling foundation.

We evaluated a simple computational model of productive vocabulary acquisition, applied to simulating two case studies of 7-year-old children with developmental word-finding difficulties across four core behavioural tasks. Developmental models were created, which captured the deficits of each child. In order to predict the effects of intervention, we exposed the computational models to simulated behavioural interventions of two types, targeting the improvement of either phonological or semantic knowledge. The model was then evaluated by testing the predictions from the simulations against the actual results from an intervention study carried out with the two children. For one child it was predicted that the phonological intervention would be effective, and the semantic intervention would not. This was borne out in the behavioural study. For the second child, the predictions were less clear and depended on the nature of simulated damage to the model. The behavioural study found an effect of semantic but not phonological intervention. Through an explicit computational simulation, we therefore employed intervention data to evaluate our theoretical understanding of the processes underlying acquisition of lexical items for production and how they may vary in children with developmental language difficulties.

A retrospective review of factors associated with vasovasostomies in United States military members.

BACKGROUND: Men seeking a vasectomy should receive counseling prior to the procedure that includes discussion of later seeking a reversal. We sought to determine demographic factors that may predispose patients to possibly later seek a vasectomy reversal. METHODS: All U.S. Military electronic health records were searched between 2000 and 2009 for either a vasectomy or vasovasostomy procedure code. Aggregate demographic information was collected and statistical analysis performed. RESULT: A total of 82,945 patients had a vasectomy of which 4,485 had a vasovasostomy resulting in a vasovasostomy-to-vasectomy rate of 5.04%. The average age at vasovasostomy was 34.9±5.0, with an average interval of 4.1±2.2 years. Men undergoing a vasectomy at a younger age were more likely to have a vasovasostomy. Various religions did have statistically significant differences. Within ethnic groups, only Native Americans [OR=1.39 (95% CI 1.198-1.614)] and Asians [OR=0.501 (95% CI 0.364-0.690)] had statistically significant differences when compared to Caucasians. Men with more children at the time of vasectomy were more likely to have a vasovasostomy. CONCLUSION: Younger men, Native Americans, and men with more children at vasectomy were more likely to undergo a vasovasostomy. The reason for these differences is unknown, but this information may assist during pre-vasectomy counseling.

Ureteropelvic junction disruption and distal ureter injury associated with a Chance fracture following a traffic accident: a case report.

A 10-year-old girl sustained a ureteropelvic junction disruption and distal ureter injury associated with the Chance fracture following a traffic accident. She was sitting on the rear seat of a car wearing a lap belt. Extensive small bowel mesenteric trauma was noted. Radiography revealed a left haemothorax with mediastinal shift and an unstable flexion-distraction vertebral fracture at L2 (Chance fracture). Subsequent intravenous pyelography demonstrated proximal extravasation from the right kidney without continuity to the upper and mid ureter, indicating a ureteropelvic junction avulsion or necrosis. Definitive surgery was delayed until day 33 because of urosepsis. Due to extensive small bowel resection, ischaemia of the ureter, and the history of urosepsis, a right subcapsular nephrectomy (rather than ureteral reconstruction) was considered the safest option for minimising further complications. It is important that trauma specialists recognise additional injuries after major trauma. Early use of a multidisciplinary approach is recommended to reduce morbidity and mortality.

Predictors of first hip fracture and mortality post fracture in older women.

BACKGROUND: Hip fracture causes significant morbidity and mortality in older women. AIM: To document factors contributing to the risk of hip fracture in older women and to assess the effect of hip fracture on subsequent mortality. METHODS: Case-control study of 89 women with hip fracture and 89 controls, with two-year follow-up. Singh index and bone mineral density were calculated. RESULTS: Osteoporotic indices did not differ significantly between cases and controls. Significant predictors of risk were sleeping tablets, perception of health as fair/poor and a lower mental status score. Patients were 3.57 times more likely to die in the first year after fracture, with no difference between the groups in year two. After adjustment, hip fracture did not remain significantly associated with mortality. Inability to walk 100 yards alone prior to fracture and lower social class were significantly associated with mortality at 12 months. Age alone was significantly associated at 12-24 months. CONCLUSIONS: Factors related to falls and fracture may be more discriminatory predictors of hip fracture risk than osteoporosis in older females. Medications for sleep should be prescribed with caution. Hip fracture may have an independent effect on one year mortality, this effect is not seen in the second year.

Supernumerary intrathoracic ribs: imaging features of two cases.

Intrathoracic supernumerary ribs are a rare congenital abnormality. The chest radiography and computed tomographic findings (including 3D reconstruction) of two cases are presented with a brief review of the literature.

Comparison of the WHO/ISUP classification and cytokeratin 20 expression in predicting the behavior of low-grade papillary urothelial tumors. World/Health Organization/Internattional Society of Urologic Pathology.

It has not been possible to identify those low-grade papillary transitional cell bladder tumors that will recur based on conventional histopathologic assessment. Both the new World Health Organization/International Society of Urologic Pathology (WHO/ISUP) classification of transitional cell papillary neoplasms and the pattern of tumor cytokeratin 20 (CK20) immunostaining have been suggested as means of improving prognostication in low-grade transitional cell tumors. Forty-nine low-grade, noninvasive papillary transitional cell tumors were identified for the period between 1984 and 1993. The recently described WHO/ISUP classification was applied, and the tumors were classified histologically as papilloma, papillary neoplasm of low malignant potential (LMP) or low-grade papillary carcinoma. After CK20 immunostaining, the expression pattern in the tumor was classified as normal (superficial) or abnormal. Of 49 tumors, 20 were classified as papillary neoplasms of LMP and five of these patients (25%) experienced a recurrence. Of 29 tumors classified as low-grade papillary carcinoma, 14 (48.2%) recurred. In 46 of 49 cases, the CK20 immunostaining could be evaluated. Sixteen tumors showed normal (superficial) pattern of CK20 expression, and four (25%) of these patients experienced a recurrence. In contrast, of 30 patients with abnormal CK20 staining of their tumors, 15 (50%) patients had one or more recurrences. In this study, papillary neoplasms of LMP (as per the WHO/ISUP classification system) had a lower recurrence rate than low-grade papillary transitional cell carcinoma. Similarly low-grade urothelial tumors showing a normal CK20 expression pattern recurred less frequently than tumors with an abnormal pattern of CK20 staining. Neither of these differences was statistically significant, and recurrences were observed in 20% of patients whose tumors were both classified as papillary neoplasms of LMP and showed normal CK20 immunostaining; thus they do not allow a change in our current management of patients with low-grade papillary urothelial tumors, with close follow-up for all patients.

The word-length effect and disyllabic words.

Three experiments compared immediate serial recall of disyllabic words that differed on spoken duration. Two sets of long- and short-duration words were selected, in each case maximizing duration differences but matching for frequency, familiarity, phonological similarity, and number of phonemes, and controlling for semantic associations. Serial recall measures were obtained using auditory and visual presentation and spoken and picture-pointing recall. In Experiments 1a and 1b, using the first set of items, long words were better recalled than short words. In Experiments 2a and 2b, using the second set of items, no difference was found between long and short disyllabic words. Experiment 3 confirmed the large advantage for short-duration words in the word set originally selected by Baddeley, Thomson, and Buchanan (1975). These findings suggest that there is no reliable advantage for short-duration disyllables in span tasks, and that previous accounts of a word-length effect in disyllables are based on accidental differences between list items. The failure to find an effect of word duration casts doubt on theories that propose that the capacity of memory span is determined by the duration of list items or the decay rate of phonological information in short-term memory.

Downregulation of the human taurine transporter by glucose in cultured retinal pigment epithelial cells.

In diabetes, activation of the aldose reductase (AR) pathway and alterations of glucose-sensitive signal transduction pathways have been implicated in depletion of intracellular taurine, an endogenous antioxidant and compatible osmolyte. Cellular taurine accumulation occurs by an osmotically induced, protein kinase C (PKC)-regulated Na(+)-taurine cotransporter (hTT). The effects of ambient glucose on taurine content, hTT activity, and hTT gene expression were therefore evaluated in low and high AR-expressing human retinal pigment epithelial cell lines. In low AR-expressing cells, 20 mM glucose decreased taurine content, hTT transporter activity, and mRNA levels, and these effects were unaffected by AR inhibition (ARI). In these cells, the inhibitory effects of high glucose on hTT appeared to be posttranscriptionally mediated, because 20 mM glucose decreased hTT mRNA stability without affecting hTT transcriptional rate. Inhibition of PKC overcame the decrease in hTT activity in high glucose-exposed cells. In high AR-expressing cells, prolonged exposure to 20 mM glucose resulted in intracellular taurine depletion, which paralleled sorbitol accumulation and was prevented by ARI. In these cells exposed to 5 mM glucose, hTT mRNA abundance was decreased and declined further in 20 mM glucose but was corrected by ARI. In 5 mM glucose, hTT transcriptional rate was markedly decreased in high AR-expressing cells, did not decline further in 20 mM glucose, but was increased by ARI to levels above those observed in low AR-expressing cells. Therefore, glucose rapidly and specifically decreases taurine content, hTT activity, and mRNA abundance by AR-unrelated and AR-related posttranscriptional and transcriptional mechanisms.

Posttraumatic stress disorder and traumatic brain injury: are they mutually exclusive?

It has been suggested that posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) must be mutually incompatible disorders. However, growing empirical evidence has begun to question this. Evidence suggests that although PTSD may be relatively rare among the TBI population, some TBI patients seem to develop PTSD. We suggest two theoretical routes through which PTSD might develop in TBI patients: through nonconscious processes in individuals who are subsequently amnesic, but who were conscious at the time of the traumatic episode and through subsequent appraisal processes in individuals who were unconscious during the traumatic episode.

Use of technology in phonological intervention.

Microcomputers can support phonological intervention in a variety of ways. Software and hardware can assist clinicians in identifying errors and establishing appropriate treatment targets. Technology can also help to determine the nature of errors so that optimal intervention methods are used. Specific technology tools for addressing phonological errors due to problems with articulation, phonemic identification, and phonetic mapping are discussed. The use of technology to document and analyze treatment performance is also addressed.

Use of technology to facilitate language skills in school-age children.

Technology offers numerous possibilities for facilitating language and literacy skills in school-age children and adolescents. Narrative skills can be addressed by the use of specialized programs as well as generic word processing software. Writing skills can be targeted due to the variety of possibilities for input as well as options for supporting spelling and syntax. Reading skills might be improved by the use of programs that focus on decoding, as well as hypertext tools that highlight the use of text patterns or signals.

Inferring sublexical correspondences from sight vocabulary: evidence from 6- and 7-year-olds.

We report an experiment designed to investigate 6-to-7-year-old children's ability to acquire knowledge of sublexical correspondences between print and sound from their reading experience. A computer database containing the printed word vocabulary of children taking part in the experiment was compiled and used to devise stimuli controlled for grapheme-phoneme correspondence (GPC) frequency and rime neighbourhood consistency according to the children's reading experience. Knowledge of GPC rules and rime units was compared by asking children to read aloud three types of nonword varying in regularity of GPC and consistency of rime pronunciation. Results supported the view that children can acquire knowledge of both GPC rules and rime units from their reading experience. GPC rule strength affects the likelihood of a GPC response; rime consistency affects the likelihood of a rime response.