bluuebunny/crossref_metadata_2025 huggingface dataset:
Ectopic bone formation in and soft‐tissue response to P(CL/DLLA)/bioactive glass composite scaffolds
Authors: Meretoja Ville V. , Tirri Teemu , Malin Minna , Seppälä Jukka V. , Närhi Timo O.
Published: October 2012

Objectives

To characterize biological response to subcutaneously implanted macroporous poly(ε‐caprolactone/D,L‐lactide)‐based scaffolds, and to evaluate the effect of bioactive glass (BAG) filler and osteogenic cells to the tissue response and ectopic bone formation.

Material and methods

In the first part of this study, six different scaffold types were screened in a rat subcutaneous implantation model. The polymer scaffolds with 70/30 caprolactone/lactide ratio and corresponding composites with < 45 μm BAG filler size were chosen for the further ectopic bone formation assay. The scaffolds were loaded with differentiating bone marrow stromal cells and implanted subcutaneously in syngeneic rats.

Results

With plain scaffolds, only mild foreign body reaction with no signs of gross inflammation was observed after 4 weeks of implantation. Furthermore, the scaffolds were fully invaded by well‐vascularized soft connective tissue. Overall, all the tested scaffold types showed an appropriate host response. With cell‐seeded scaffolds, several loci of immature mineralizing tissue and small amounts of mature bone were observed after 4 weeks. The incidence of mature bone formation was two and four in polymer scaffolds and composites, respectively (n = 8). After twelve weeks, mature bone was observed in only one polymer scaffold but in seven composites (n = 8). Excluding bone formation, the host response was considered similar to that with cell‐free scaffolds.

Conclusions

Plain scaffolds supported the ingrowth of well‐vascularized fibroconnective tissue. Furthermore, cell seeded composites with BAG filler showed enhanced ectopic bone formation in comparison with corresponding neat polymer scaffolds.
Involvement of Acetylcholine‐α7nAChR in the Protective Effects of Arterial Baroreflex against Ischemic Stroke
Authors: Liu Ai‐Jun , Zang Pu , Guo Jin‐Min , Wang Wei , Dong Wen‐Zhe , Guo Wei , Xiong Zhi‐Gang , Wang Wei‐Zhong , Su Ding‐Feng
Published: October 2012

Aims

Decreased baroreflex sensitivity is associated with poor outcome in many cardiovascular diseases including stroke, but the molecular mechanism underlying this relationship is unclear. This work was designed to test the hypothesis that acetylcholine (ACh) and α7 nicotinic ACh receptor (α7nAChR) mediate the protection of arterial baroreflex against stroke.

Methods

Sinoaortic denervation (SAD) was used to impair the function of arterial baroreflex, and anticholinesterase agents were used to activate the cholinergic system and increase endogenous ACh. Middle cerebral artery occlusion (MCAO) was performed in the α7nAChR knockout (KO) mice and Sprague–Dawley rats.

Results

We found decreased expression of vesicular ACh transporter (VAChT) and α7nAChR in rat brain after SAD. In rats subjected to MCAO, neostigmine significantly reduced the infarct size. The protective effects of neostigmine were abolished by selective nAChR antagonist vecuronium but not by mAChR antagonist anisodamine. In addition, the effect of neostigmine disappeared in α7nAChR KO mice. In cultured neurons, ACh inhibited cell death induced by H2O2. In cultured microglial cells, ACh decreased the release of proinflammatory cytokines induced by lipopolysaccharide. These in vitro effects were blocked by selective α7nAChR antagonists.

Conclusion

Taken together, these findings indicate that the ACh‐α7nAChR involved in the protective effects of arterial baroreflex against ischemic stroke.
Laparoscopic ventral mesh rectopexy in the management of solitary rectal ulcer syndrome: a cause for optimism?
Authors: Badrek‐Amoudi A. H. , Roe T. , Mabey K. , Carter H. , Mills A. , Dixon A. R.
Published: October 2012

Aim

The treatment of solitary rectal ulcer syndrome (SRUS) is notoriously difficult. Laparoscopic ventral mesh rectopexy (LVMR) is a nonresectional technique for patients with full thickness external rectal prolapse and internal prolapse with obstructed defaecation syndrome (ODS), features associated in the pathogenesis of SRUS. Our aim was to assess the short‐ and long‐term efficacy of LVMR in treating SRUS.

Method

Forty‐eight patients with SRUS who underwent LVMR over a 15‐year period (December 1996 to July 2012) were identified from a prospectively maintained electronic database.

Results

Forty‐eight patients, 38 (79%) women, median age 43 (18–80) years, median body mass index 26 (21–40) kg/m2 underwent LVMR for SRUS after initial biofeedback. The median follow‐up was 33 months (95% CI 31–55, range 1–186 months); 52% were followed for more than 3 years and 13 (27%) for more than 5 years. Five (10%) had relapsed following a response to stapled transanal rectal resection (STARR; 10 additional patients have had a continued response to STARR). Eleven (23%) had intermittent reducible external prolapse. Epithelial ulcer healing was reported in all patients at 3 months. The ODS scores improved by 68% (P < 0.0001) and quality of life (QoL; Birmingham Bowel and Urinary Symptoms Questionnaire‐22) scores improved by 45% (P < 0.0001). There was a significant improvement in bowel visual analogue scale (VAS) scores at 3 and 12 months (P = 0.0007). Sustained improvement in QoL and VAS scores was maintained at 2 years and continued in the 52% followed up for between 3 and 15 years. There were four (8%) symptomatic ODS recurrences: posterior rectal wall prolapse successfully treated by STARR (3) and one symptom free for 2 years following a temporary loop ileostomy. There were two recurrences (4%).

Conclusion

LVMR appears to provide a sustained improvement in QoL, VAS and patient satisfaction in patients with SRUS. Morbidity, recurrence and safety profiles are low.
Pine wilt disease: detection of the pinewood nematode (Bursaphelenchus xylophilus) as a tool for a pine breeding programme
Authors: Ribeiro B. , Espada M. , Vu T. , Nóbrega F. , Mota M. , Carrasquinho I.
Published: October 2012

The pinewood nematode (PWN), Bursaphelenchus xylophilus, is a serious quarantine pest first detected in Portugal and Europe in 1999. It is the causal agent of pine wilt disease (PWD). A resistance breeding programme has been initiated to contribute to control the evolution of the disease. Five hundred and four adult maritime pine, Pinus pinaster, trees were phenotypically selected as candidate trees for this programme from an area affected by PWD. To identify tolerance to the nematode, the selected trees were monitored monthly. Over the course of 1 year, 57 candidate trees died and were tested for the presence/absence of the PWN. As accuracy of detection is of major importance, an ITS‐PCR‐based method applied directly to wood from adult maritime pine trees was tested and compared with a standard morphological identification method. The results showed that the use of PCR to detect the pathogen provided more rapid and accurate results in comparison with the standard morphological identification. Thus, this method is suitable to be used in the survey of the breeding population for resistance/tolerance to PWD.
Lmx1a is an activator of Rgs4 and Grb10 and is responsible for the correct specification of rostral and medial mdDA neurons
Authors: Hoekstra Elisa J. , von Oerthel Lars , van der Linden Annemarie J. A. , Schellevis Raymond D. , Scheppink Gerard , Holstege Frank C. P. , Groot‐Koerkamp Marian J. , van der Heide Lars P. , Smidt Marten P.
Published: October 2012

The LIM homeodomain transcription factor Lmx1a is a very potent inducer of stem cells towards dopaminergic neurons. Despite several studies on the function of this gene, the exact in vivo role of Lmx1a in mesodiencephalic dopamine (mdDA) neuronal specification is still not understood. To analyse the genes functioning downstream of Lmx1a, we performed expression microarray analysis of LMX1A‐overexpressing MN9D dopaminergic cells. Several interesting regulated genes were identified, based on their regulation in other previously generated expression arrays and on their expression pattern in the developing mdDA neuronal field. Post analysis through in vivo expression analysis in Lmx1a mouse mutant (dr/dr) embryos demonstrated a clear decrease in expression of the genes Grb10 and Rgs4, in and adjacent to the rostral and dorsal mdDA neuronal field and within the Lmx1a expression domain. Interestingly, the DA marker Vmat2 was significantly up‐regulated as a consequence of increased LMX1A dose, and subsequent analysis on Lmx1a‐mutant E14.5 and adult tissue revealed a significant decrease in Vmat2 expression in mdDA neurons. Taken together, microarray analysis of an LMX1A‐overexpression cell system resulted in the identification of novel direct or indirect downstream targets of Lmx1a in mdDA neurons: Grb10, Rgs4 and Vmat2.
rTMS over human motor cortex can modulate tremor during movement
Authors: Rogasch Nigel C. , Todd Gabrielle
Published: October 2012

Abnormally large tremor during movement is a symptom of many movement disorders and significantly impairs activities of daily living. The aim of this study was to investigate whether repetitive magnetic brain stimulation (rTMS) can reduce tremor size during human movement. We hypothesised that inhibitory rTMS over motor cortex would reduce tremor size during subsequent movement. The study involved 26 healthy young adults (21 ± 2 years) and began with application of single TMS stimuli to measure baseline corticospinal excitability. The response to stimulation was recorded in hand muscles with electromyography. Subjects then performed a 3‐min task to measure baseline tremor during movement. This involved matching index finger position with a moving target on a computer screen. Tremor was recorded with an accelerometer on the fingernail. Finger acceleration was analysed with fast‐Fourier transform to quantify tremor in the physiological range (7.8–12.2 Hz). Subjects then received 10 min of real (n = 13) or sham (n = 13) inhibitory rTMS. Tremor and corticospinal excitability were then remeasured. Real rTMS significantly decreased corticospinal excitability by ~30% (P = 0.022) and increased tremor size during movement by ~120% (P = 0.047) relative to sham rTMS. However, the direction of tremor change was opposite to that hypothesised for inhibitory rTMS. The results suggest that rTMS over human motor cortex can modulate action tremor and the level of corticospinal excitability may be important for setting the amplitude of action tremor in healthy young adults.
Effects of the α2‐adrenergic receptor agonist dexmedetomidine on neural, vascular and BOLD fMRI responses in the somatosensory cortex
Authors: Fukuda Mitsuhiro , Vazquez Alberto L. , Zong Xiaopeng , Kim Seong‐Gi
Published: October 2012

This article describes the effects of dexmedetomidine (DEX) – the active ingredient of medetomidine, which is the latest popular sedative for functional magnetic resonance imaging (fMRI) in rodents – on multiple unit activity, local field potential (LFP), cerebral blood flow (CBF), pial vessel diameter [indicative of cerebral blood volume (CBV)], and blood oxygenation level‐dependent (BOLD) fMRI. These measurements were obtained from the rat somatosensory cortex during 10 s of forepaw stimulation. We found that the continuous intravascular systemic infusion of DEX (50 μg/kg/h, doses typically used in fMRI studies) caused epileptic activities, and that supplemental isoflurane (ISO) administration of ~0.3% helped to suppress the development of epileptic activities and maintained robust neuronal and hemodynamic responses for up to 3 h. Supplemental administration of N2O in addition to DEX nearly abolished hemodynamic responses even if neuronal activity remained. Under DEX + ISO anesthesia, spike firing rate and the delta power of LFP increased, whereas beta and gamma power decreased, as compared with ISO‐only anesthesia. DEX administration caused pial arteries and veins to constrict nearly equally, resulting in decreases in baseline CBF and CBV. Evoked LFP and CBF responses to forepaw stimulation were largest at a frequency of 8–10 Hz, and a non‐linear relationship was observed. Similarly, BOLD fMRI responses measured at 9.4 T were largest at a frequency of 10 Hz. Both pial arteries and veins dilated rapidly (artery, 32.2%; vein, 5.8%), and venous diameter returned to baseline slower than arterial diameter. These results will be useful for designing, conducting and interpreting fMRI experiments under DEX sedation.
Neural regulation of the time course for cocaine‐cue extinction consolidation in rats
Authors: Szalay, Jonathan J. , Jordan Chloe J. , Kantak Kathleen M.
Published: October 2012

Sites within the hippocampus, amygdala and prefrontal cortex may regulate how responses maintained by cues associated with cocaine are extinguished. To test the role of various brain sites in the consolidation of cocaine‐cue extinction learning, the dorsal subiculum (dSUB), rostral basolateral amygdala (rBLA) and infralimbic prefrontal cortex (IL) were manipulated in rats. Following cocaine self‐administration training (cues present, cocaine available), responding was assessed during 1‐h extinction tests (cues present, no cocaine available). To study extinction consolidation specifically, the protein synthesis inhibitor anisomycin or vehicle was infused bilaterally into the dSUB, rBLA or IL either immediately following or 6 h after the first two of three extinction training sessions. With manipulations made immediately after extinction sessions, infusions of anisomycin into the dSUB or the rBLA deterred extinction. Rats maintained elevated levels of cocaine seeking relative to vehicle despite the absence of cocaine delivery. Manipulations of IL had no effect. Control studies showed that bilateral protein synthesis inhibition in dSUB and rBLA 6 h after the extinction sessions ended was unable to deter extinction. Rats reduced cocaine seeking in the usual manner in the absence of cocaine delivery. Collectively, these findings suggest that the dSUB and rBLA are neural substrates important for consolidation of cocaine‐cue extinction learning and have time‐dependent roles. Understanding the contribution of individual neural substrates for cocaine‐cue extinction consolidation may help guide treatment strategies aimed at enhancing cue exposure therapy in cocaine‐dependent people.
Major vault protein promotes locomotor recovery and regeneration after spinal cord injury in adult zebrafish
Authors: Pan Hong‐Chao , Lin Jin‐Fei , Ma Li‐Ping , Shen Yan‐Qin , Schachner Melitta
Published: October 2012

In contrast to mammals, adult zebrafish recover locomotor functions after spinal cord injury (SCI), in part due to axonal regrowth and regeneration permissivity of the central nervous system. Upregulation of major vault protein (MVP) expression after spinal cord injury in the brainstem of the adult zebrafish prompted us to probe for its contribution to recovery after SCI. MVP is a multifunctional protein expressed not only in many types of tumours but also in the nervous system, where its importance for regeneration is, however, unclear. Using an established zebrafish SCI model, we found that MVP mRNA and protein expression levels were increased in ependymal cells in the spinal cord caudal to the lesion site at 6 and 11 days after SCI. Double immunolabelling showed that MVP was co‐localised with Islet‐1 or tyrosine hydroxylase around the central canal of the spinal cord in sham‐injured control fish and injured fish 11 days after surgery. MVP co‐localised with the neural stem cell marker nestin in ependymal cells after injury. By using an in vivo morpholino‐based knock‐down approach, we found that the distance moved by MVP morpholino‐treated fish was reduced at 4, 5 and 6 weeks after SCI when compared to fish treated with standard control morpholino. Knock‐down of MVP resulted in reduced regrowth of axons from brainstem neurons into the spinal cord caudal to the lesion site. These results indicate that MVP supports locomotor recovery and axonal regrowth after SCI in adult zebrafish.
Medical management of sand enteropathy in 62 horses
Authors: Hart K. A. , Linnenkohl W. , Mayer J. R. , House A. M. , Gold J. R. , Giguère S.
Published: October 2012

Reasons for performing study

Medical management of sand enteropathy is common in equine practice, but the clinical features and outcomes associated with medically managed sand enteropathy are not well described.

Objectives

To review clinical features, therapeutic approaches and outcomes associated with primary medical management of sand enteropathy in the mature horse.

Methods

Medical record databases at 3 equine referral hospitals fromJanuary 2000 toApril 2010 were reviewed for cases of sand enteropathy diagnosed via abdominal radiographs in mature horses that were initially managed medically. Data were collected and descriptive analyses compiled. Uni‐ and multivariate logistic regression was used to evaluate factors potentially associated with treatment failure.

Results

The medical records of 62 horses were analysed; 90% of horses survived to discharge and 50% of horses that had repeat abdominal radiographs taken demonstrated improvement in the degree of sand accumulation after treatment. Nine horses underwent exploratory laparotomy during hospitalisation, and colonic sand impaction was found in all 9, with a concurrent gastrointestinal lesion identified in 7. Four horses were subjected to euthanasia during or after surgery because of disease severity or complications. Need for exploratory laparotomy was the factor most strongly associated with nonsurvival.

Conclusions

These data suggest that medical management can result in clinical and radiographic resolution of uncomplicated sand enteropathy in mature horses, and is associated with a good prognosis. Horses with sand enteropathy that exhibit persistent colic signs despite medical management are likely to have a concurrent gastrointestinal lesion, so prompt exploratory laparotomy should be considered in such cases.

Potential relevance

Uncomplicated sand enteropathy can be managed medically in mature horses, and serial abdominal radiography can be used to monitor sand clearance. Surgery to evaluate for and correct concurrent gastrointestinal lesions should be recommended without delay in horses showing persistent colic signs.
Androgen receptor association with mitotic chromatin – analysis with introduced deletions and disease‐inflicting mutations
Authors: Kumar Sanjay , Tyagi Rakesh K.
Published: October 2012

Sequence and structural anomalies in the gene for androgen receptor (AR) or its protein are associated with a range of clinical manifestations. Observations from living cells have shown that AR translocates to the nucleus upon ligand binding, where it forms typical ‘nuclear foci’ that are considered as sites of gene transcription. Recently, we reported the ligand‐mediated association of AR with mitotic chromatin and suggested its role in ‘transcription memory’, proposing a ‘biopit model’. In the present study, we show that each of the AR domains is obligatory for its association with mitotic chromatin and also that full‐length AR is necessary for efficient association. In addition, deletion or point mutations in bipartite nuclear localization signal (NLS) revealed impaired localization, ‘nuclear foci’ formation and abolished AR binding with mitotic chromatin. Interestingly, well‐characterized AR‐NLS mutants associated with the manifestation of pathological conditions (prostate cancer and androgen‐insensitivity syndrome) exhibited differential behaviour on mitotic chromatin and also impaired receptor localization and ‘nuclear foci’ formation. Finally, we report that, in addition to its functions in nuclear import, DNA binding, acetylation, N/C‐termini interactions and transactivation, the AR‐NLS region also functions as ‘mitotic chromatin binding‐determining region’ and has a novel role in the regulation of the AR association with mitotic chromatin.
SET overexpression decreases cell detoxification efficiency: ALDH2 and GSTP1 are downregulated, DDR is impaired and DNA damage accumulates
Authors: Almeida Luciana O. , Goto Renata N. , Pestana Cezar R. , Uyemura Sérgio A. , Gutkind Silvio , Curti Carlos , Leopoldino Andréia M.
Published: October 2012

Alcohol and tobacco consumption are risk factors for head and neck squamous cell carcinoma (HNSCC). Aldehyde dehydrogenase 2 (ALDH2) and glutathione S–transferase pi 1 (GSTP1) are important enzymes for cellular detoxification and low efficiencies are implicated in cancer. We assessed the potential role of SET protein overexpression, a histone acetylation modulator accumulated in HNSCC, in gene regulation and protein activity of ALDH2 and GSTP1. SET was knocked down in HN13, HN12 and Cal27, and overexpressed in HEK293 cells; ethanol and cisplatin were the chemical agents. Cells with SET overexpression (HEK293/SET, HN13 and HN12) showed lower ALDH2 and GSTP1 mRNA levels and trichostatin A increased them (real‐time PCR). Ethanol upregulated GSTP1 and ALDH2 mRNAs, whereas cisplatin upregulated GSTP1 in HEK293 cells. SET‐chromatin binding revealed SET interaction with ALDH2 and GSTP1 promoters, specifically via SET NAP domain; ethanol and cisplatin abolished SET binding. ALDH2 and GSTP1 efficiency was assessed by enzymatic and comet assay. A lower ALDH2 activity was associated with greater DNA damage (tail intensity) in HEK293/SET compared with HEK293 cells, whereas HN13/siSET showed ALDH2 activity higher than HN13 cells. HN13/siSET cells showed increased tail intensity. Cisplatin‐induced DNA damage response showed negative relationship between SET overexpression and BRCA2 recruitment. SET downregulated repair genes ATM, BRCA1 and CHEK2 and upregulated TP53. Cisplatin‐induced cell‐cycle arrest occurred in G0/G1 and S in HEK293 cells, whereas HEK293/SET showed G2/M stalling. Overall, cisplatin was more cytotoxic for HN13 than HN13/siSET cells. Our data suggest a role for SET in cellular detoxification, DNA damage response and genome integrity.
Response: complexities of sustainable forest use
Authors: Haberl Helmut , Schulze Ernst‐Detlef , Körner Christian , Law Beverly E. , Holtsmark Bjart , Luyssaert Sebastiaan
Published: October 2012

This is a response to the Editorial Commentary by Schulze et al
The serrated pathway to colorectal carcinoma: current concepts and challenges
Authors: Bettington Mark , Walker Neal , Clouston Andrew , Brown Ian , Leggett Barbara , Whitehall Vicki
Published: October 2012

Approximately 30% of colorectal carcinomas develop via a serrated neoplasia pathway, named for the pattern of crypts in the precursor polyps. Molecular abnormalities consistently involve methylation of CpG islands [CpG island methylator phenotype (CIMP)] of low degree (CIMP‐L) or high degree (CIMP‐H), and activating mutations of the mitogen‐activated protein kinase pathway components BRAF or KRAS. Microsatellite instability (MSI) of a high level (MSI‐H) is often present, allowing for a molecular classification of serrated pathway carcinoma as: (i) BRAF mutant/CIMP‐H with either a) MSI‐H or b) microsatellite stable (MSS); and (ii) KRAS mutant/CIMP‐L/MSS. Precursor polyps include sessile serrated adenoma (SSA), characterized by proximal location, crypt architectural disturbance, and BRAF mutation. Microvesicular hyperplasic polyp (MVHP) probably precedes the development of SSA, and borderline lesions between MVHP and SSA occur. Cytological dysplasia in SSA portends advanced genetic abnormality and a high risk of progression to carcinoma. The traditional serrated adenoma has a predilection for the left colon, tubulovillous architecture, eosinophilic cytoplasm, and frequent KRAS mutation. Serrated morphology carcinoma is a new World Health Organization subtype with well‐differentiated, mucinous or trabecular patterns. It has frequent KRAS or BRAF mutations and a poor prognosis. This review provides an insight into the histology and molecular mechanisms driving these serrated pathway lesions.
Epithelial–mesenchymal transition in carcinomas of the female genital tract
Authors: Stewart Colin J R , McCluggage W Glenn
Published: October 2012

Invasion is a defining feature of malignancy, but the mechanisms of invasion in many common cancers, including gynaecological malignancies, remain unclear. However, it has been proposed that malignant cells may usurp a normal embryological process, epithelial–mesenchymal transition (EMT), as a means of acquiring migratory capacity. The synergistic role of the tumour microenvironment in EMT induction has also been explored and helps to explain the spatially restricted distribution of EMT at the deep tumour margin (invasive front). Furthermore, tumour cells undergoing EMT may acquire cancer stem cell characteristics, and this may be relevant to the entire metastatic process and to tumour recurrence and treatment failure. Nevertheless, doubts persist regarding the role of EMT in malignant progression in vivo, partly because few studies have correlated molecular and histological alterations in clinical pathology specimens. In the current review we summarize the evidence for EMT in the common gynaecological epithelial malignancies, and discuss the morphological and immunohistochemical changes occurring at the invasive tumour front that may represent EMT‐like processes. The possibility that carcinosarcomas represent a variant type of EMT with ‘fixed’ mesenchymal differentiation is also considered. Diagnostic histopathologists are ideally placed to critically evaluate the role of EMT in gynaecological and other types of malignancy.
Differences in the profile of neonatal abstinence syndrome signs in methadone‐ versus buprenorphine‐exposed neonates
Authors: Gaalema Diann E. , Scott Teresa Linares , Heil Sarah H. , Coyle Mara G. , Kaltenbach Karol , Badger Gary J. , Arria Amelia M. , Stine Susan M. , Martin Peter R. , Jones Hendrée E.
Published: October 2012

Aims

To compare the profile of signs of neonatal abstinence syndrome (NAS) in methadone‐ versus buprenorphine‐exposed infants.

Design, setting and participants

Secondary analysis of NAS data from a multi‐site, double‐blind, double‐dummy, flexible‐dosing, randomized clinical trial. Data from a total of 129 neonates born to opioid‐dependent women who had been assigned to receive methadone or buprenorphine treatment during pregnancy were examined.

Measurements

For 10 days after delivery, neonates (methadone = 72, buprenorphine = 57) were assessed regularly using a 19‐item modified Finnegan scale. Data from neonates who required pharmacological treatment (methadone = 41, buprenorphine = 27) were included up to the time treatment was initiated. The incidence and mean severity of the total NAS score and each individual sign of NAS were calculated and compared between medication conditions, as was the median time until morphine treatment initiation among treated infants in each condition.

Findings

Two NAS signs (undisturbed tremors and hyperactive Moro reflex) were observed significantly more frequently in methadone‐exposed neonates and three (nasal stuffiness, sneezing, loose stools) were observed more frequently in buprenorphine‐exposed neonates. Mean severity scores on the total NAS score and five individual signs (disturbed and undisturbed tremors, hyperactive Moro reflex, excessive irritability, failure to thrive) were significantly higher among methadone‐exposed neonates, while sneezing was higher among buprenorphine‐exposed neonates. Among treated neonates, methadone‐exposed infants required treatment significantly earlier than buprenorphine‐exposed infants (36 versus 59 hours postnatal, respectively).

Conclusions

The profile of neonatal abstinence syndrome differs in methadone‐ versus buprenorphine‐exposed neonates, with significant differences in incidence, severity and treatment initiation time. Overall, methadone‐exposed neonates have a more severe neonatal abstinence syndrome.
Neonatal neurobehavior effects following buprenorphine versus methadone exposure
Authors: Coyle Mara G. , Salisbury Amy L. , Lester Barry M. , Jones Hendrée E. , Lin Hai , Graf‐Rohrmeister Klaudia , Fischer Gabriele
Published: October 2012

Aim

To determine the effects of in utero exposure to methadone or buprenorphine on infant neurobehavior.

Design

Three sites from the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study, a double‐blind, double‐dummy, randomized clinical trial participated in this substudy.

Setting

Medical Centers that provided comprehensive maternal care to opioid‐dependent pregnant women in Baltimore, MD, Providence, RI and Vienna, Austria.

Participants

Thirty‐nine full‐term infants.

Measurements

The Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS) was administered to a subgroup of infants on postpartum days 3, 5, 7, 10, 14–15 and 28–30.

Findings

While neurobehavior improved for both medication conditions over time, infants exposed in utero to buprenorphine exhibited fewer stress‐abstinence signs (P < 0.001), were less excitable (P < 0.001) and less over‐aroused (P < 0.01), exhibited less hypertonia (P < 0.007), had better self‐regulation (P < 0.04) and required less handling (P < 0.001) to maintain a quiet alert state relative to in utero methadone‐exposed infants. Infants who were older when they began morphine treatment for withdrawal had higher self‐regulation scores (P < 0.01), and demonstrated the least amount of excitability (P < 0.02) and hypertonia (P < 0.02) on average. Quality of movement was correlated negatively with peak NAS score (P < 0.01), number of days treated with morphine for NAS (P < 0.01) and total amount of morphine received (P < 0.03). Excitability scores were related positively to total morphine dose (P < 0.03).

Conclusion

While neurobehavior improves during the first month of postnatal life for in utero agonist medication‐exposed neonates, buprenorphine exposure results in superior neurobehavioral scores and less severe withdrawal than does methadone exposure.
Opioid dependence during pregnancy: relationships of anxiety and depression symptoms to treatment outcomes
Authors: Benningfield Margaret M. , Dietrich Mary S. , Jones Hendrée E. , Kaltenbach Karol , Heil Sarah H. , Stine Susan M. , Coyle Mara G. , Arria Amelia M. , O'Grady Kevin E. , Fischer Gabriele , Martin Peter R.
Published: October 2012

Aims

To examine the relationship of anxiety and depression symptoms with treatment outcomes (treatment discontinuation, rates of ongoing use of illicit drugs and likelihood of preterm delivery) in opioid‐dependent pregnant women and describe their use of psychotropic medications.

Design and setting

Secondary data analysis from a randomized clinical trial of treatment for opioid dependence during pregnancy.

Participants

A total of 175 opioid‐dependent pregnant women, of whom 131 completed treatment.

Measurements

Symptoms of anxiety and depression were captured with the 15‐item Mini International Neuropsychiatric Interview (MINI) screen. Use of illicit drugs was measured by urine drug screening. Preterm delivery was defined as delivery prior to 37 weeks' gestation. Self‐reported use of concomitant psychotropic medication at any point during the study was recorded.

Findings

Women reporting only anxiety symptoms at study entry were more likely to discontinue treatment [adjusted odds ratio (OR) = 4.56, 95% confidence interval (CI): 1.91–13.26, P = 0.012], while those reporting only depression symptoms were less likely to discontinue treatment (adjusted OR = 0.14, 95% CI: 0.20–0.88, P = 0.036) compared to women who reported neither depression nor anxiety symptoms. No statistically significant between‐group differences were observed for ongoing illicit drug use or preterm delivery. A majority (61.4%) of women reported use of concomitant psychotropic medication at some point during study participation.

Conclusions

Opioid agonist‐treated pregnant patients with co‐occurring symptoms of anxiety require additional clinical resources to prevent premature discontinuation.
Comparison between 8‐prenylnarigenin and narigenin concerning their activities on promotion of rat bone marrow stromal cells’ osteogenic differentiation in vitro
Authors: Ming L. G. , Ge B. F. , Wang M. G. , Chen K. M.
Published: October 2012

A number of recent studies have suggested that flavonols (a class of phytochemical with many biological activities), might exert protective effects against post‐menopausal bone loss. In the present study, we compared naringenin (NG) and 8‐prenylnaringenin (PNG), two major naturally occurring flavonols, on in vitro differentiation of osteoblasts and bone resorbing activity, of rat bone marrow stromal cells (BMSCs). Our results indicated that both compounds, at 10−6 m, enhanced BMSCs’ differentiation. Then effects of the two compounds at 10−6 m on ALP activity, osteocalcin secretion and calcium deposition, were compared over a time course. Numbers and areas of colonies stained for ALP (CFU‐FALP) expression, and mineralized bone nodules, were histochemically analysed after 12 days and 16 days osteogenic induction, respectively. Expression of BMP‐2, OPG, OSX, RUNX‐2 genes and p38MAPK protein were examined using real‐time PCR and western blotting, respectively. The data presented indicate that PNG, significantly enhanced the rat BMSCs’ differentiation and mineralization through the BMP‐2/p38MAPK/Runx2/Osterix signal pathway, greater than did NG. In conclusion, PNG has a more pronounced ability to enhance osteoblast differentiation and mineralization, than NG.
Oridonin: targeting programmed cell death pathways as an anti‐tumour agent
Authors: Liu Z. , Ouyang L. , Peng H. , Zhang W.‐Z.
Published: October 2012

Oridonin, an active diterpenoid isolated from traditional Chinese herbal medicine, has drawn rising attention for its remarkable apoptosis‐ and autophagy‐inducing activity and relevant molecular mechanisms in cancer therapy. Apoptosis is a well known type of cell death, whereas autophagy can play either pro‐survival or pro‐death roles in cancer cells. Accumulating evidence has recently revealed relationships between apoptosis and autophagy induced by oridonin; however, molecular mechanisms behind them remain to be discovered. In this review, we focus on highlighting updated research on oridonin‐induced cell death signalling pathways implicated in apoptosis and autophagy, in many types of cancer. In addition, we further discuss cross‐talk between apoptosis and autophagy induced by oridonin, in cancer. Taken together, these findings open new perspectives for further exploring oridonin as a potential anti‐tumour agent targeting apoptosis and autophagy, in future anti‐cancer therapeutics.
Exposure of immunologically naive laboratory rodents to antigen via the airways. Where does tolerance stop and sensitization begin?
Authors: Guibas G. V. , Makris M. , Spandou E. , Priftis K. N.
Published: October 2012

Conventional rodent models of respiratory allergy that employ intraperitoneal sensitization to aeroallergen plus adjuvant, have offered greatly to our current knowledge of the pathophysiology of allergic airway diseases. Notwithstanding this significant contribution, non‐adjuvant aided sensitization via respiratory presentation of the allergen, is more naturally relevant and more closely mimics the human exposure. Nevertheless, in the experimental setting, primary respiratory exposure to inert antigen is likely to lead to inhalation tolerance. Inasmuch as divergent and discrepant results are often reported in experimental models employing this method of sensitization, we set out to review the relative literature and identify and discuss factors that are liable to interfere in such protocols and modify the immune response, hence leading to variable outcomes. Protocol design features (including the use of anaesthesia, the nature and dosage of the antigen and the strain/age/sex and handling of the animals) as well as environmental factors (including airborne substances, viruses and lipopolysaccharide) have been identified as key modulators of the immune response that evolves, following primary airway exposure of laboratory rodents to aeroallergen. Delineation of the effect of those factors to induction or abrogation of inhalation tolerance can have important implications in the design of both improved experimental protocols of respiratory allergy and methods to intercept sensitization to inert aeroallergens in the clinical field.
Health self‐advocacy training for persons with intellectual disabilities
Authors: Feldman M. A. , Owen F. , Andrews A. , Hamelin J. , Barber R. , Griffiths D.
Published: October 2012

Background

People with intellectual disabilities (ID) have unequal access to health care. While systemic efforts are addressing health inequalities, there remains a need to demonstrate that persons with ID can increase their health self‐advocacy skills.

Method

A randomised control design with up to 6‐month follow‐up was used to evaluate the 3Rs (Rights, Respect and Responsibility) health self‐advocacy training program for persons with ID (n = 31). Training involved teaching participants to recognise and redress health rights violations in the context of respect and responsibility. Training materials included PowerPoint slides and interactive video scenarios illustrating health rights, respect and responsibility problem and non‐problems. Two‐hour training sessions were conducted twice a week in a group format where participants played a game and answered questions.

Results

The health rights training group made significantly more correct responses on post training and follow‐up tests than the control group. Training effects generalised to untrained scenarios and in situ health interviews.

Conclusions

The results of this study suggest that persons with ID can learn complex skills related to health self‐advocacy. More research is needed to improve in situ generalisation.
The voting rights of adults with intellectual disabilities: reflections on the arguments, and situation in Kenya and England and Wales
Authors: Redley M. , Maina E. , Keeling A. , Pattni P.
Published: October 2012

Article 29 of the Convention on the Rights of Persons with Disabilities guarantees equality of political rights, including the right to vote and stand for election. The affirmation of these rights, first guaranteed by the Universal Declaration of Human Rights, raises an important question given the long‐standing association between political rights and beliefs concerning the abilities of citizens to reason and act independently: how and to what degree can people identified as having intellectual disabilities participate in a defining act of the democratic process? Focused specifically on the right to vote, this paper addresses the question by (1) introducing the debates that have surrounded the voting rights of this population; and (2) reporting on recent attempts in Kenya, and in England and Wales, to promote voting by people with intellectual disabilities. It concludes by considering the effectiveness of the different approaches these countries have adopted.
Service development for intellectual disability mental health: a human rights approach
Authors: Evans E. , Howlett S. , Kremser T. , Simpson J. , Kayess R. , Trollor J.
Published: October 2012

Background

People with intellectual disability (ID) experience higher rates of major mental disorders than their non‐ID peers, but in many countries have difficulty accessing appropriate mental health services. The aim of this paper is to review the current state of mental health services for people with ID using Australia as a case example, and critically appraise whether such services currently meet the standards set by the Convention on the Rights of Persons with Disabilities.

Methods

The literature regarding the current state of mental health services for people with ID was reviewed, with a particular focus on Australia.

Results

The review highlighted a number of issues to be addressed to meet the mental health needs of people with ID to ensure that their human rights are upheld like those of all other citizens. Many of the barriers to service provision encountered in Australia are likely also to be relevant to other nations, including the culture of division between disability and mental health services, the inadequate training of both disability and mental health workers in ID mental health, and the lack of relevant epidemiological data. None of these barriers are insurmountable.

Conclusions

Recommendations are made for adopting a human rights‐based approach towards the development and provision of mental health services for people with ID. These include improved policy with measurable outcomes, improved service access via clear referral pathways and the sharing of resources across disability and mental health services, and improved service delivery through training and education initiatives for both the mental health and disability workforce.
Effects of eutrophication and temperature on Cyclotella rhomboideo‐ellipticaSkuja, endemic diatom to China
Authors: Li Yan‐ling , Gong Zhi‐jun , Shen Ji
Published: October 2012

An endemic diatom, Cyclotella rhomboideo‐elliptica Skuja, from the Yunnan Plateau, has been disappearing gradually from some lakes of the plateau. This study investigated the diatom's distribution in 30 lakes and documents long‐term population changes in the paleolimnological record of a deep lake, Lake Fuxian. Living cells of C. rhomboideo‐elliptica were found in five Yunnan Plateau lakes in 1957, but cells were restricted to Lake Fuxian in 2005. Its absolute abundance fluctuated from low to high to low. Our study suggests that nutrient concentrations correlate with C. rhomboideo‐elliptica's s abundance and survival. We infer that the disappearance of C. rhomboideo‐elliptica in some lakes may be due to increased nutrient concentrations and the species may be indicators of low nutrients. During the study, we also found that decreased in the diatoms average long axis length after the early 1990s. This morphological change was likely due to higher nutrient concentrations or to the increase in temperature, or a combination of the two.
Wordlikeness and word learning in children with hearing loss
Authors: Stiles Derek J. , McGregor Karla K. , Bentler Ruth A.
Published: October 2012

Background

The more a novel word conforms to the phonotactics of the language, the more wordlike it is and the easier it is to learn. It is unknown to what extent children with hearing loss (CHL) take advantage of phonotactic cues to support word learning.

Aims

This study investigated whether CHL had similar sensitivities to wordlikeness during a word‐learning task as children with normal hearing (CNH).

Methods & Procedures

Sixteen CHL and 24 CNH participated in a novel word‐learning task. Novel words varied by English wordlikeness. Recall was tested using a forced‐choice identification task wherein foils for each trial related semantically, lexically or not at all. Receptive vocabulary and working memory were also assessed.

Outcomes & Results

All children were able to identify high wordlike novel words more accurately than low wordlike novel words. The number of errors on identification of words that were moderate in wordlikeness was inversely correlated to vocabulary size (not working memory) and CHL had smaller vocabularies than CNH. When in error, CHL were more likely than CNH to select a semantically related foil.

Conclusions & Implications

Although they are sensitive to extremes in wordlikeness, compared with their peers with normal hearing, CHL present with subtle differences in word learning. Clinical implications for exploiting wordlikeness in service of word learning assessment and intervention are presented.
Class matters: 12‐month‐olds’ word–object associations privilege content over function words
Authors: MacKenzie Heather , Curtin Suzanne , Graham Susan A.
Published: October 2012

A fundamental step in learning words is the development of an association between a sound pattern and an element in the environment. Here we explore the nature of this associative ability in 12‐month‐olds, examining whether it is constrained to privilege particular word forms over others. Forty‐eight infants were presented with sets of novel English content‐like word–object pairings (e.g. fep) or novel English function‐like word–object (e.g. iv) pairings until they habituated. Results indicated that infants associated novel content‐like words, but not the novel function‐like words, with novel objects. These results demonstrate that the mechanism with which basic word–object associations are formed is remarkably sophisticated by the onset of productive language. That is, mere associative pairings are not sufficient to form mappings. Rather the system requires well‐formed noun‐like words to co‐occur with objects in order for the linkages to arise.
Visual size perception and haptic calibration during development
Authors: Gori Monica , Giuliana Luana , Sandini Giulio , Burr David
Published: October 2012

It is still unclear how the visual system perceives accurately the size of objects at different distances. One suggestion, dating back to Berkeley’s famous essay, is that vision is calibrated by touch. If so, we may expect different mechanisms involved for near, reachable distances and far, unreachable distances. To study how the haptic system calibrates vision we measured size constancy in children (from 6 to 16 years of age) and adults, at various distances. At all ages, accuracy of the visual size perception changes with distance, and is almost veridical inside the haptic workspace, in agreement with the idea that the haptic system acts to calibrate visual size perception. Outside this space, systematic errors occurred, which varied with age. Adults tended to overestimate visual size of distant objects (over‐compensation for distance), while children younger than 14 underestimated their size (under‐compensation). At 16 years of age there seemed to be a transition point, with veridical perception of distant objects. When young subjects were allowed to touch the object inside the haptic workspace, the visual biases disappeared, while older subjects showed multisensory integration. All results are consistent with the idea that the haptic system can be used to calibrate visual size perception during development, more effectively within than outside the haptic workspace, and that the calibration mechanisms are different in children than in adults.