Maternal Perceptions of Infant Behavior as a Potential Indicator of Parents or Infants in Need of Additional Support and Intervention.

The goal of the present study is to examine the relationship between early infant behaviors, which can be easily reported by parents, with parent-infant bonding and maternal mental health. It has long been established that child characteristics and behaviors have a significant impact on parent well-being and how parents respond to their infants. Examining parent perceptions of challenging infant behaviors may help health professionals identify high risk infants in need of intervention and mothers in need of additional support. Mothers of 73 infants between the ages of 3.5 weeks and 6 months filled out questionnaires. Infant stomach issues were positively correlated with bonding issues, maternal anxiety and maternal depression. Infant crying issues were also positively correlated with bonding issues, maternal anxiety and maternal depression. Potential clinical and research applications of the instrument include early identification of caregivers in need of support and screening for further clinical assessment and care.

Gesture Frequency and Function in Infants With Fragile X Syndrome and Infant Siblings of Children With Autism Spectrum Disorder.

Purpose Infant siblings of children with autism spectrum disorder (ASIBs) and infants with fragile X syndrome (FXS) are both at risk for developing autism spectrum disorder (ASD) and communication disorders; however, very few studies have examined 1 of the earliest forms of intentional communication in infants from these groups: gestures. This study examined the frequency and function of gesture use across 12-month-old infant ASIBs, infants with FXS, and low-risk controls. Method Participants included 23 ASIBs who did not later meet diagnostic criteria for ASD, 18 infants with FXS, and 21 low-risk controls. Gestures were coded from a semistructured play-based interaction. Results Overall, infants with FXS displayed fewer gestures than low-risk infants, whereas ASIBs did not differ from the FXS or low-risk groups in overall gesture frequency. In terms of the communicative function of the gestures used, the FXS and ASIB groups displayed significantly fewer social interaction gestures than the low-risk controls, with large effect sizes. Conclusion This study contributes to scant knowledge of early communication phenotypes of infant ASIBs who do not meet criteria for ASD and infants with FXS. Results indicated that gesture function, not frequency, best discriminated at-risk infants from low-risk infants at 12 months of age. Findings have implications for the clinical evaluation and treatment of infants at high risk for ASD and communication disorders.

Bifidobacterium breve reduces apoptotic epithelial cell shedding in an exopolysaccharide and MyD88-dependent manner.

Certain members of the microbiota genus Bifidobacterium are known to positively influence host well-being. Importantly, reduced bifidobacterial levels are associated with inflammatory bowel disease (IBD) patients, who also have impaired epithelial barrier function, including elevated rates of apoptotic extrusion of small intestinal epithelial cells (IECs) from villi-a process termed 'cell shedding'. Using a mouse model of pathological cell shedding, we show that mice receiving Bifidobacterium breve UCC2003 exhibit significantly reduced rates of small IEC shedding. Bifidobacterial-induced protection appears to be mediated by a specific bifidobacterial surface exopolysaccharide and interactions with host MyD88 resulting in downregulation of intrinsic and extrinsic apoptotic responses to protect epithelial cells under highly inflammatory conditions. Our results reveal an important and previously undescribed role for B. breve, in positively modulating epithelial cell shedding outcomes via bacterial- and host-dependent factors, supporting the notion that manipulation of the microbiota affects intestinal disease outcomes.

Desmopressin treatment improves platelet function under flow in patients with postoperative bleeding.

BACKGROUND: Patients undergoing major cardiothoracic surgery are subjected to dilution, owing to massive fluid infusion and blood component transfusion. These patients may experience bleeding perioperatively, and are frequently treated with the endothelium-activating agent desmopressin. OBJECTIVES: To investigate the effect of desmopressin administration on von Willebrand factor (VWF)-dependent coagulant and platelet functions under flow conditions. PATIENTS/METHODS: Blood from 16 patients with postoperative bleeding was obtained before and after desmopressin treatment (0.3 µg kg(-1) body weight), and assessed for coagulant properties and platelet function. Furthermore, VWF antigen levels and multimer composition were determined in both samples. RESULTS: Desmopressin treatment did not change thrombin generation in plasma or whole blood thromboelasticity. Also coagulation factor levels (other than factor VIII) and coagulation times were unchanged, suggesting that desmopressin treatment did not have a major effect on the coagulant activity. On the other hand, desmopressin treatment raised the already high plasma levels of VWF from a median of 116 IU mL(-1) (interquartile range [IQR] 102-154 IU mL(-1) ) to a median of 160 IU mL(-1) (IQR 126-187 IU mL(-1) ) (P = 0.007), owing to accumulation of the high molecular weight VWF multimers. Furthermore, desmopressin treatment caused an increase in collagen-dependent thrombus formation and platelet phosphatidylserine exposure. Markers of thrombus formation correlated with the plasma levels of VWF. In vitro control experiments confirmed a major contribution of VWF to thrombus formation and procoagulant activity under conditions of blood dilution. CONCLUSIONS: Desmopressin treatment of patients with bleeding complications after cardiothoracic surgery induces the release of high molecular weight VWF multimers, which enhance platelet activation and thrombus formation under flow conditions.

Toll-like receptor expression in crypt epithelial cells, putative stem cells and intestinal myofibroblasts isolated from controls and patients with inflammatory bowel disease.

The aim of our studies was to investigate the expression of Toll-like receptor (TLR)-2 and TLR-4 (and in some studies TLR-5) in myofibroblasts and small and large intestinal crypt epithelial cells from control patients and those affected by Crohn's disease and ulcerative colitis. Isolated and disaggregated crypt epithelial cells and monolayers of myofibroblasts were used for studies by reverse transcription-polymerase chain reaction (RT-PCR), real-time RT-PCR, flow cytometry, immunocytochemistry and Western blot analysis. Compared to control cells, crypt epithelial cells isolated from active ulcerative colitis and Crohn's disease colonic mucosal samples showed significantly higher expression of TLR-2 and TLR-4 transcripts and protein (on the cell surface). There was also enhanced expression of TLR-4 in crypt cells from ileal Crohn's disease. Expression of TLR-2 and TLR-4 transcripts in crypt epithelial cells isolated from inflamed mucosa of distal ulcerative colitis did not differ significantly from such cells obtained from the normal proximal colon. Crypt epithelial cells with side population characteristics (putative stem cells) also expressed transcripts and protein for TLR-2, TLR-4 and TLR-5. Colonic myofibroblast expression of these TLRs was much weaker than in crypt epithelial cells. In conclusion, enhanced TLR-2 and TLR-4 expression by crypt epithelial cells in active inflammatory bowel disease likely reflects greater ability to respond to microbial products. Results from our studies using mucosal samples from patients with distal ulcerative colitis suggest that the enhanced expression of these TLRs could be constitutive. TLR-2, TLR-4 and TLR-5 expression by stem cells imply ability to respond to distinct bacterial products.

Primary human colonic myofibroblasts are resistant to Clostridium difficile toxin A-induced, but not toxin B-induced, cell death.

Colonic inflammation in Clostridium difficile infection is mediated by released toxins A and B. We investigated responses to C. difficile toxins A and B by isolated primary human colonic myofibroblasts, which represent a distinct subpopulation of mucosal cells that are normally located below the intestinal epithelium. Following incubation with either purified toxin A or B, there was a change in myofibroblast morphology to stellate cells with processes that were immunoreactive for alpha-smooth muscle actin. Most of the myofibroblasts remained viable, with persistence of stellate morphology, despite exposure to high concentrations (up to 10 µg/ml) of toxin A for 72 h. In contrast, a majority of the toxin B-exposed myofibroblasts lost their processes prior to cell death over 24 to 72 h. At low concentrations, toxin A provided protection against toxin B-induced cell death. Within 4 h, myofibroblasts exposed to either toxin A or toxin B lost expression of the nonglucosylated form of Rac1, and there was also a loss of the active form of RhoA. Despite preexposure to high concentrations of toxin A for 3 h, colonic myofibroblasts were able to recover their morphology and proliferative capacity during prolonged culture in medium. However, toxin B-preexposed myofibroblasts were not able to recover. In conclusion, primary human colonic mucosal myofibroblasts are resistant to toxin A (but not toxin B)-induced cell death. Responses by colonic myofibroblasts may play an important role in mucosal protection, repair, and regeneration in colitis due to C. difficile infection.

Expression profiling of Wnt family of genes in normal and inflammatory bowel disease primary human intestinal myofibroblasts and normal human colonic crypt epithelial cells.

BACKGROUND: Wnt signaling regulates intestinal epithelial stem cell function. Wnt ligands bind Frizzled (Fz) receptors and low-density lipoprotein-receptor-related protein (LRP) 5 and 6. Secreted Frizzled-related protein (SFRP) and Dickkopf families inhibit Wnt signaling. Our aim was to study expression of Wnt family of genes in isolated intestinal myofibroblasts and crypt epithelial cells. METHODS: Myofibroblasts were isolated from normal colonic and small intestinal mucosal samples and those affected by ulcerative colitis (UC) and Crohn's disease. Expression of the Wnt family of genes was studied by polymerase chain reaction (PCR) array. Epithelial proliferation was studied using IEC-6 cells. RESULTS: Most of the myofibroblast isolates expressed Wnt2, Wnt5A, Wnt5B, Fzd1, Fzd2, Fzd4, Fzd6, Fzd7, Fzd8, LRP6, Dickkopf1, and SFRP1. Compared to myofibroblasts isolated from normal colonic mucosal samples, real-time reverse transcription-PCR studies (using additional isolates) showed significantly reduced expression of SFRP1 in UC myofibroblasts (3.34-fold reduction, P < 0.01). Recombinant SFRP1 inhibited proliferation of IEC-6 epithelial cells. In colonic crypt epithelial cells, expression of Wnt ligands and their inhibitors was generally either absent or very weak. By contrast, all the crypt epithelial preparations expressed Fzd1, Fzd5, Fzd7, Fzd8, and LRP6. CONCLUSIONS: Human intestinal myofibroblasts expressed a number of Wnt ligands, their receptors, and inhibitors. In contrast, colonic crypt epithelial cells predominantly expressed Wnt receptors. Compared to myofibroblasts isolated from normal colonic mucosa, those affected by UC showed significantly reduced expression of SFRP1. Since reduced SFRP1 expression has been associated with malignancy, low myofibroblast expression of this Wnt inhibitor may be implicated in increased risk of cancer in UC.

An argument for orogastric tubes during caesarean section.

Routine orogastric aspiration of stomach contents during general anaesthesia for caesarean section was recommended in the latest triennial report on maternal deaths. We conducted a postal survey which revealed that the majority of obstetric units do not follow this guideline. Following the report, we aspirated the stomach contents of all our patients undergoing general anaesthesia for caesarean section and analysed the aspirate volume and pH. Despite routine antacid prophylaxis, a large proportion of our emergency patients remain at risk for aspiration pneumonia. We thus concur with the recommendation that the stomach should be aspirated during general anaesthesia for emergency caesarean section.

Aortic pH oscillations in conscious humans and anaesthetised cats and rabbits.

Respiratory oscillations in arterial blood gas composition influence breathing in cats and dogs. Their role in the control of breathing in humans in less certain. To determine whether oscillations are very small or absent in mammals who are large or breathe fast, aortic pH oscillations, recorded with a tridodecylamine based hydrogen-ion selective electrode, were compared in humans (n = 13), cats (n = 7) and rabbits (n = 4) over a wide range of ventilation. For comparison, data were analysed in terms of the ratio of tidal volume to functional residual capacity (VT/FRC). During spontaneous breathing in rabbits, cats and humans (mean respiratory frequency fR = 61, 20.4 and and 17.5 min-1), mean VT/FRC were 1.35, 0.63 and 0.36 respectively. Corresponding pH amplitudes (pHamp) of 0.009 (0.004), 0.016 and 0.013 (0.005) pH units (mean +/- 1SD) were not significantly different. The pHamp decreased exponentially with increasing FR in each species and pHamp increased linearly with increasing VT in the 3 cats in which this was studied. The study confirms the dependence of pHamp on FR and VT and its comparability among species despite differences in body size. It also demonstrates that oscillations can be recorded in humans at FR in excess of 20 min-1.

Fluid requirements of patients with burns and inhalation injuries in an intensive care unit.

We have studied 9 patients with burns (20%-75%) who had inhalation injuries and compared their actual fluid requirements with their requirements calculated from the Muir and Barclay formula. All patients were resuscitated with plasma protein fraction at a rate sufficient to keep their physiological variables within the following range: heart rate less than 120/min, central venous pressure 8-12 cm H2O, urine output greater than 30-50 ml/h, systolic blood pressure greater than 90 mm Hg and diastolic blood pressure greater than 60 mm Hg. The amount of plasma protein fraction needed was 4.38 +/- 1.26 ml/kg/% burn in the first 24 h and 2.15 +/- 0.97 ml/kg/% burn in the second 24 h. This is an increase of 75% and 110% respectively above values predicted from the formula. We suggest that the observed difference is due to a combination of the presence of an inhalation injury which increases fluid requirements by approximately 30% in the first 24 h and the use of plasma protein fraction rather than the dried plasma used in the original Muir and Barclay formula.

Masked vitamin B12 and folate deficiency in the elderly.

1. A high incidence of vitamin B12 or folate deficiency, or both, may be found in the elderly, particularly those in hospital. This report concerns fifty cases detected in an inner-city-area geriatric unit during the course of routine clinical investigation. The majority had none of the classical haematological signs of vitamin B12 or folate deficiency, and all the patients reported had a mean corpuscular volume (MCV) of less than 100 fl. 2. There was a significant negative correlation between the MCV and the erythrocyte folate (P less than 0.01), supporting earlier published work using a low serum folate as an index of folate deficiency. 3. There was no correlation between the MCV and the serum vitamin B12. Published work differs on this point. 4. Serum iron, total Fe-binding capacity and percentage Fe saturation results were available in forty patients in this series. There was a significant positive correlation between the serum Fe and the MCV (P less than 0.01) and 34% of patients had haematological evidence of Fe deficiency. In the majority, however, there was no evidence that associated Fe deficiency had masked the haematological signs of vitamin B12 or folate deficiency. 5. More attention should be paid to the problem of 'masked' vitamin B12 and folate deficiency in the elderly. There is a case for routine screening of the elderly for vitamin B12 and folate deficiency irrespective of the MCV.

Neostriatal administration of somatostatin:differential effect of small and large doses on behavior and motor control.

The administration of small doses of somatostatin (SRIF) (0.01 and 0.1 microgram) into the neostriatal complex of unrestrained, freely moving rats induced general behavioral excitation associated with a variety of stereotyped movements, tremors, and a reduction of rapid eye movements (REM) and deep slow wave sleep (SWS). In contrast, the higher doses of SRIF (1.0 and 10.0 microgram) caused movements to be uncoordinated and frequently induced more severe difficulties in motor control such as contralateral hemiplegia-in-extension which restricted or completely prevented the expression of normal behavioral patterns. As a result, the animals appeared drowsy and inhibited. Analysis of the sleep-waking cycle revealed prolonged periods of a shallow SWS while REM sleep and deep SWS were markedly reduced; electroencephalogram recordings revealed periods of dissociation from behavior. The administration of endocrinologically inactive as well as the active analogues of SRIF failed to induce effects comparable with those observed after the administration of the same dose of the native hormone (10.0 microgram).

Cortical administration of somatostatin (SRIF): effect on sleep and motor behavior.

Cortical administration of SRIF in unrestrained, freely moving rats produced an early activation, stereotyped behavior patterns and later, coordination difficulties often associated with drowsiness. A few animals showed a tendency toward paraplegia-in-extension. A considerable, prolonged alteration in the sleep-waking cycle was also observed. Similar results were obtained in both intact and hypophysectomized animals. Intraperitoneal administration of SRIF induced several other effects in addition to those seen after cortical application. The latter were however, restricted in variety, intensity and duration.