Central opioid receptors differentially regulate the nalmefene-induced suppression of ethanol- and saccharin-reinforced behaviors in alcohol-preferring (P) rats.

The exact opioid-sensitive receptors participating in EtOH-seeking behaviors remains unclear. Previous studies have reported higher densities of micro-opioid receptor binding in the nucleus accumbens (NACC) of P relative to NP rats; however, no differences were seen in delta-receptor binding. In contrast to the NACC, substantially lower levels of micro-receptor binding have been observed in the ventral tegmental area (VTA) of both P and NP rats, albeit no line differences have been observed. In the present study, opioid receptors in the NACC, VTA, and hippocampus were evaluated for their capacity to regulate both EtOH- and saccharin-motivated behaviors in the genetically selected alcohol-preferring (P) rat. To accomplish this, nalmefene, an opiate antagonist with preferential binding affinity for the micro-opioid receptor was unilaterally or bilaterally infused during concurrent availability of 1 h daily EtOH (10% v/v) and saccharin (0.025 or 0.050% w/v) solutions. Rats performed under a two-lever fixed ratio (FR) schedule in which four responses on one lever produced the EtOH solution, and four on a second lever produced the saccharin solution. The results demonstrated that when responding maintained by both EtOH and saccharin are matched at basal levels, unilateral (1-60 microg) or bilateral (0.5-10 microg) microinjections of nalmefene into the NACC produced selective dose-dependent reductions on responding maintained by EtOH. Unilateral (40, 60 microg) and bilateral (10 microg) VTA infusions were also observed to selectively reduced EtOH responding; however, greater nalmefene doses were required and the magnitude of suppression on EtOH responding was markedly less compared with the NACC. The greater sensitivity of nalmefene to suppress EtOH responding in the NACC is likely due to the greater number of opioid receptors in the NACC relative to the VTA. Only bilateral infusion of the 40 microg dose in the NACC and VTA suppressed responding maintained by both EtOH and saccharin. In contrast, intrahippocampal infusions dose dependently suppressed EtOH- and saccharin-maintained responding over a range of doses (1-20 microg). The present study provides evidence that nalmefene suppresses EtOH-motivated behaviors via blockade of opioid receptors within the NACC and VTA, and under various dose conditions both reinforcer and neuroanatomical specificity can be observed.     

Early reconstruction of the abdominal wall in giant omphalocele.

Omphalocele is the most common congenital defect of the abdominal wall. Mortality rate is between 20 and 70% and early closure of the abdominal wall, within 10 days of life, is vital to the successful outcome of the surgical treatment. The authors describe the use of two bipedicled flaps of abdominal skin to correct the defect of the midline as soon as the reduction of all viscera has been accomplished.     

Comparison of different MRI sequences in lesion detection and early response evaluation of diffuse large B‐cell lymphoma – a whole‐body MRI and diffusion‐weighted imaging study

To compare different MRI sequences for the detection of lesions and the evaluation of response to chemotherapy in patients with diffuse large B‐cell lymphoma (DLBCL), 18 patients with histology‐confirmed DLBCL underwent 3‐T MRI scanning prior to and 1 week after chemotherapy. The MRI sequences included T₁‐weighted pre‐ and post‐contrast, T₂‐weighted with and without fat suppression, and a single‐shot echo‐planar diffusion‐weighted imaging (DWI) with two b values (0 and 800 s/mm²). Conventional MRI sequence comparisons were performed using the contrast ratio between tumor and normal vertebral body instead of signal intensity. The apparent diffusion coefficient (ADC) of the tumor was measured directly on the parametric ADC map. The tumor volume was used as a reference for the evaluation of chemotherapy response. The mean tumor volume was 374 mL at baseline, and decreased by 65% 1 week after chemotherapy (p < 0.01). The T₂‐weighted image with fat suppression showed a significantly higher contrast ratio compared with images from all other conventional MRI sequences, both before and after treatment (p < 0.01, respectively). The contrast ratio of the T₂‐weighted image with fat suppression decreased significantly (p < 0.01), and that of the T₁‐weighted pre‐contrast image increased significantly (p < 0.01), after treatment. However, there was no correlation between the change in contrast ratio and tumor volume. The mean ADC value was 0.68 × 10^–3 mm²/s at baseline; it increased by 89% after chemotherapy (p < 0.001), and the change in ADC value correlated with the change in tumor volume (r = 0.66, p < 0.01). The baseline ADC value also correlated inversely with the percentage change in ADC after treatment (r = ?0.62, p < 0.01). In conclusion, this study indicates that T₂‐weighted imaging with fat suppression is the best conventional sequence for the detection of lesions and evaluation of the efficacy of chemotherapy in DLBCL. DWI with ADC mapping is an imaging modality with both diagnostic and prognostic value that could complement conventional MRI. Copyright © 2013 John Wiley & Sons, Ltd.     

Independent Origin of Plasmodium falciparum Antifolate Super-Resistance,Uganda, Tanzania,and Ethiopia

Super-resistant Plasmodium falciparum threatens the effectiveness of sulfadoxine–pyrimethamine in intermittent preventive treatment for malaria during pregnancy. It is characterized by the A581G Pfdhps mutation on a background of the double-mutant Pfdhps and the triple-mutant Pfdhfr. Using samples collected during 2004–2008, we investigated the evolutionary origin of the A581G mutation by characterizing microsatellite diversity flanking Pfdhps triple-mutant (437G+540E+581G) alleles from 3 locations in eastern Africa and comparing it with double-mutant (437G+540E) alleles from the same area. In Ethiopia, both alleles derived from 1 lineage that was distinct from those in Uganda and Tanzania. Uganda and Tanzania triple mutants derived from the previously characterized southeastern Africa double-mutant lineage. The A581G mutation has occurred multiple times on local Pfdhps double-mutant backgrounds; however, a novel microsatellite allele incorporated into the Tanzania lineage since 2004 illustrates the local expansion of emergent triple-mutant lineages.     

Investigation of Self-Healing Mortars with and without Bagasse Ash at Pre- and Post-Crack Times

Cracks in typical mortar constructions enhance water permeability and degrade ions into the structure, resulting in decreased mortar durability and strength. In this study, mortar samples are created that self-healed their cracks by precipitating calcium carbonate into them. Bacillus subtilus bacterium (10⁻⁷, 10⁻⁹ cells/mL), calcium lactate, fine aggregate, OPC-cement, water, and bagasse ash were used to make self-healing mortar samples. Calcium lactates were prepared from discarded eggshells and lactic acid to reduce the cost of self-healing mortars, and 5% control burnt bagasse ash was also employed as an OPC-cement alternative. In the presence of moisture, the bacterial spores in mortars become active and begin to feed the nutrient (calcium lactate). The calcium carbonate precipitates and plugs the fracture. Our experimental results demonstrated that cracks in self-healing mortars containing bagasse ash were largely healed after 3 days of curing, but this did not occur in conventional mortar samples. Cracks up to 0.6 mm in self-healing mortars were filled with calcite using 10⁻⁷ and 10⁻⁹ cell/mL bacteria concentrations. Images from an optical microscope, X-ray Diffraction (XRD), and a scanning electron microscope (SEM) were used to confirm the production of calcite in fractures. Furthermore, throughout the pre- and post-crack-development stages, self-healing mortars have higher compressive strength than conventional mortars. The precipitated calcium carbonates were primed to compact the samples by filling the void spaces in hardened mortar samples. When fissures developed in hardened mortars, bacteria became active in the presence of moisture, causing calcite to precipitate and fill the cracks. The compressive strength and flexural strength of self-healing mortar samples are higher than conventional mortars before cracks develop in the samples. After the healing process of the broken mortar parts (due to cracking), self-healing mortars containing 5% bagasse ash withstand a certain load and have greater flexural strength (100 kPa) than conventional mortars (zero kPa) at 28 days of cure. Self-healing mortars absorb less water than typical mortar samples. Mortar samples containing 10⁻⁷ bacteria cells/mL exhibit greater compressive strength, flexural strength, and self-healing ability. XRD and SEM were used to analyze mortar samples with healed fractures. XRD, FTIR, and SEM images were also used to validate the produced calcium lactate. Furthermore, the durability of mortars was evaluated using DTA-TGA analysis and water absorption tests.     

Field efficacy of thermally expelled or live potted repellent plants against African malaria vectors in western Kenya

OBJECTIVE: To estimate the effectiveness of live potted plants and thermal expulsion of plant materials in repelling African malaria vectors in traditional houses in western Kenya. METHODS: Ocimum americanum, Lantana camara and Lippia ukambensis were tested in live, intact potted form whereas leaves of Corymbia citriodora, leaves and seeds of O. kilimandscharicum and O. suave were tested by thermal expulsion from modified traditional stoves. A latin square design was applied for randomly assigning the treatment and control plants to experimental houses over different nights. RESULTS: All plant species showed significant repellency against Anopheles gambiae sensu lato Giles (Diptera: Culicidae) (81.5%An. arabiensis Patton and 18.5%An. gambiae sensu stricto Giles), the main vectors of malaria in Africa, with the highest repellency by C. citriodora (48.71%, P < 0.0001) followed by an equal level of repellency of O. kilimandscharicum and O. suave (44.54%, P = 0.001) during application of plant material by thermal expulsion. All three plant species also showed a residual effect against An. gambiae s.l. with 36-44% repellency post-application period (22.30-06.30 hours) after a period of thermal expulsion. Similarly, intact potted plants of O. americanum and L. camara repelled An. gambiae s.l. significantly (37.91%, P = 0.004; and 27.22%, P = 0.05, respectively). Thermal expulsion of leaves and seeds of O. kilimandscharicum significantly repelled An. funestus Giles, although none of the potted plants repelled this species. CONCLUSION: Both methods of application may offer cost-effective alternatives as additional means of household protection, and a useful complement to bed nets, particularly for the early part of the evening before bedtime.     

Traditional use of mosquito-repellent plants in western Kenya and their evaluation in semi-field experimental huts against Anopheles gambiae: ethnobotanical studies and application by thermal expulsion and direct burning

Ethnobotanical survey in 2 communities in western Kenya revealed that the most commonly known repellent plants were Ocimum americanum L. (64.1%), Lantana camara L. (17.9%), Tagetes minuta L. (11.3%) and Azadirachta indica A. Juss (8.7%) on Rusinga Island, and Hyptis suaveolens Poit. (49.2%), L. camara (30.9%) and O. basilicum L. (30.4%) in Rambira. Direct burning of plants is the most common method of application for O. americanum (68.8%), L. camara (100%) and O. basilicum (58.8%). Placing branches or whole plants inside houses is most common for H. suaveolens (33.3 and 57.8% for the respective locations), A. indica (66.7 and 100%), and T. minuta (54.8 and 56.0%). The repellency of plants suggested by the ethnobotanical survey and other empirical information was evaluated against the malaria vector Anopheles gambiae s.s. Giles in experimental huts within a screenwalled greenhouse. Thermal expulsion and direct burning were tested as alternative application methods for the selected plants O. americanum, O. kilimandscharicum Guerke, O. suave Willd., L. camara, A. indica, H. suaveolens, Lippia uckambensis Spreng and Corymbia citriodora Hook. When thermally expelled, only H. suaveolens failed to repel mosquitoes, whereas the leaves of C. citriodora (74.5%, P < 0.0001), leaves and seeds of O. suave (53.1%, P < 0.0001) and O. kilimandscharicum (52.0%, P < 0.0001) were the most effective. Leaves of C. citriodora also exhibited the highest repellency (51.3%, P < 0.0001) by direct burning, followed by leaves of L. uckambensis (33.4%, P = 0.0004) and leaves and seeds of O. suave (28.0%, P = 0.0255). The combination of O. kilimandscharicum with L. uckambensis repelled 54.8% of mosquitoes (P < 0.0001) by thermal expulsion. No combination of plants increased repellency by either method. The semi-field system described appears a promising alternative to full-field trials for screening large numbers of candidate repellents without risk of malaria exposure.     

Antenatal diagnosis of diaphragmatic hernia: parents' emotional and cognitive reactions

Purpose

The aim of this study was to assess parent’s emotional and cognitive reactions to the prenatal diagnosis of diaphragmatic hernia in their prospective children.

Methods

A survey was conducted by means of a questionnaire. In the period ranging from 1997 to 2002, 40 couples in whom an established diagnosis of diaphragmatic hernia was made in their fetus were seen for prenatal consultation at a tertiary referral center.

Results

Overall response rate was 93% (37 couples). Mean period since diagnosis for compilation of the questionnaire was 2 weeks. Mean gestational age at diagnosis was 25 weeks (range, 16 to 35 weeks). All parents lacked prediagnostic knowledge of diaphragmatic hernia and consider a single consultation with the paediatric surgeon inadequate to have a clear understanding of the anomaly. Only 1 mother and 1 father reported they understood all the information given by the surgeon. The most frequent (75%) feeling during and after the consultation was fear. Most parents (70%) referred to the intense emotions as the factor that made it difficult to follow the surgeon’s explanations as well as to ask questions.

Conclusions

Because of the incompatibility of emotional distress and optimum learning, impairment of early comprehension of information about diaphragmatic hernia is unavoidable. Therefore, we believe that follow-up antenatal consultations and provision of written and visual illustration are extremely important to facilitate informed choices.     

Impact of a current treatment protocol on outcome of high-risk congenital diaphragmatic hernia

Background

There is considerable debate regarding the optimal management of congenital diaphragmatic hernia (CDH) in high-risk infants (those cases presenting with respiratory distress within 2 hours of birth or those diagnosed prenatally). The aim of this study was to analyze patient outcomes using a new treatment protocol for CDH in a tertiary care non-extracorporeal membrane oxygenation (ECMO) neonatal unit.

Methods

The records of 78 consecutive neonates with CDH presenting to Bambino Gesù Children’s Hospital from 1996 to 2001 were analyzed retrospectively. Of these infants, 70 high-risk patients were identified (prenatal diagnosis or respiratory distress requiring intubation and assisted ventilation within 2 hours after birth), regardless of associated anomalies, medical condition on presentation, or degree of pulmonary hypoplasia. A prenatal diagnosis was made in 46 of 70 (66%) patients. Associated lethal malformations were present in 6 of the children (8.5%). The patients were placed in 3 historical groups: group 1, 19 patients from 1996 to 1997, group 2, 22 patients from 1998 to 1999, and group 3, 29 patients from 2000 to 2001. In the first 2 groups, a new protocol was introduced using inhaled nitric oxide (iNO) and high-frequency oxygen ventilation (HFOV). In the third group, gentle ventilation and permissive hypercarbia were also used routinely. Mortality and severe morbidity—defined as O₂ requirement at discharge, need for a tracheostomy, neurologic impairment, or bilateral hearing loss—were evaluated when the patients were at 6 months old. Univariate analysis was performed.

Results

The 3 groups were comparable with respect to predictive risk factors such as side of hernia, prenatal diagnosis, polyhydramnios, stomach and liver in the thorax, associated lethal malformations, and patch. Overall survival rate significantly increased from 47% (9 of 19) in group 1 and 50% (11 of 22) in group 2 to 90% (26 of 29) in group 3 (P = .02). None of the 19 patients in group 1 had severe morbidity compared with 2 of 22 (9%) patients in group 2 and 2 of 29 (7%) patients in group 3. Hearing loss was observed in 4 patients. Mortality rate and preoperative pneumothorax significantly decreased in group 3 compared with groups 1 and 2 (P = .03 and P = .00, respectively).

Conclusions

(1) The application of new treatment protocol for CDH, using gentle ventilation and permissive hypercarbia, produced a significant increase in survival with concomitant decrease in morbidity. (2) The rate of pneumothorax was significantly decreased by the introduction of permissive hypercarbia and gentle ventilation. (3) As more infants survive CDH without the use of ECMO, severe long-term sequelae of CDH can be recognized in these children.     

Bipedicled skin flaps for reconstruction of the abdominal wall in newborn omphalocele

Despite technical refinements in surgery and advances in postoperative intensive care, abdominal wall closure in giant omphalocele remains a difficult endeavor. In this respect, bipedicled skin flaps obtained with longitudinal incisions along the margins of the rectus abdominis muscle may represent a good alternative solution to achieve a complete, tension-free midline closure. Incisional areas can subsequently be easily covered with split-thickness thigh grafts. Two neonatal cases were treated with this technique with good results. This has enabled avoidance of palliative coverage as well as complex musculo-cutaneous reconstructions at a later age.