bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of Early-Onset Spinal Deformity (EOSD) With VEPTR
Authors: Lattig Friederike , Taurman Rita , Hell Anna K. 
Published: August 2012

Study Design:
Case Series.

Objective:
To describe the post-VEPTR (vertical expandable prosthetic titanium rib) treatment changes in early-onset spinal deformity (EOSD), which may influence the final correction spondylodesis.

Summary of Background Data:
The VEPTR device, originally developed for the treatment of congenital rib cage malformation, is nowadays more widely used in the treatment of EOSD. At present, only a few reports describe the possible complications that may occur with repeated lengthening procedures of the VEPTR, thereby making the final spondylodesis more complicated and less satisfactory.

Methods:
X-rays of 5 children treated for EOSD with 2 unilateral VEPTR (each rib to rib and rib to lumbar lamina) were analyzed for curve patterns and Cobb angles before, during, and at the end of VEPTR treatment, and after the final spondylodesis. Intraoperative observations during the spondylodesis, which influenced the possibilities of the curve correction, were documented.

Results:
All patients showed a marked decompensation of the frontal balance and a high degree of rigidity of the main curve and the compensatory curves after treatment with the VEPTR device. Because of this spontaneous autofusion of spinal segments, migration of the rib cradles and/or the laminar hook, and a change in the curve patterns, the final fusion had to be longer in all patients than the primary deformity would have intended.

Conclusions:
If an EOSD is treated with VEPTR, the curve progression and, in particular, the development of a high thoracic hyperkyphosis or rotation of the main curve should be critically observed. Autofusion of ribs and vertebral bodies may make the final correction spondylodesis even more challenging and risky for the patient and the end result less satisfactory.
PEEK Cages in Lumbar Fusion
Authors: Schimmel Janneke J. P. , Poeschmann Marcel S. , Horsting Philip P. , Schönfeld Dirk H. W. , van Limbeek Jacques , Pavlov Paul W. 
Published: August 2012

Study Design:
Historical cohort analysis.

Objective:
Evaluation of mid-term clinical outcome and radiologic fusion in patients treated with a polyetheretherketone (PEEK) cage.

Summary of Background Data:
Anterior lumbar interbody fusion can be a good alternative in chronic low back pain when conservative treatment fails. Although titanium alloy cages give good fusion rates, disadvantages are the subsidence of the cage in the adjacent vertebrae and problematic radiologic evaluation of fusion. PEEK cages such as the Synfix-LR cage (Synthes, Switzerland) should overcome this.

Methods:
From December 2004 until August 2007, 95 patients (21 double-level and 74 single-level) with degenerative disk disease from L3–S1 were operated by a single surgeon. The number of reoperations was counted. Radiologic fusion on computed tomography scan was scored with a new scoring system by an independent skeletal radiologist and orthopedic surgeon. Intraobserver agreement and specificity were assessed. Clinical improvement was measured by the Oswestry Disability Index score. The median duration of clinical follow-up was 47.7 months (range 29.9–61.6).

Results:
In total, 26 patients were reoperated after a median period of 17.6 months (range 6.7–46.9) of the initial surgery. Of the 26 patients, 23 patients (18 single-level and 5 double-level) were reoperated for symptomatic pseudarthrosis. A moderate agreement (κ=0.36) and a specificity of 70% and 37% for the radiologist and orthopedic surgeon, respectively, were found for scoring bony bridging. The Oswestry Disability Index score improved after initial surgery; however, reoperated patients reported a significantly lower improvement.

Conclusions:
A high number of reoperations after an anterior lumbar interbody fusion procedure with the Synfix-LR cage were found, mainly because of symptomatic pseudarthrosis. The absence of posterior fixation in combination with lower stiffness and the hydrophobic characteristics of PEEK probably lead to insufficient initial stability, creating suboptimal conditions for bony bridging, and thus solid fusion. The proposed ease of the evaluation of radiologic fusion could not be supported. Clinicians should be alert on pseudarthrosis when patients treated with the Synfix-LR cage presented with persisted or aggravated complaints.
Malignant Peripheral Nerve Sheath Tumor
Authors: Tracy Jennifer A. , Rubin Devon I. , Amrami Kimberly K. , Spinner Robert J. , Engelstad JaNean K. , Scheithauer Bernd W. , Dyck P. James B. 
Published: August 2012

Abstract
We present the case of a 67-year-old man with a malignant peripheral nerve sheath tumor (MPNST) affecting the brachial plexus. He presented with progressive right upper extremity paresthesias, numbness, weakness, and severe pain. Nerve conduction studies/electromyography demonstrated a right lower and middle trunk predominant brachial plexopathy. Three-tesla magnetic resonance imaging of the brachial plexus showed a soft tissue mass with central necrosis and cystic changes and irregular contrast enhancement. Positron emission tomography showed increased fluorodeoxyglucose uptake within the mass. Targeted fascicular nerve biopsy revealed hypercellular tumor, featuring atypical cells with mitotic figures and limited immunoreactivity for S-100 protein. The findings were those of an MPNST. The effects on the variably involved fascicles were also seen in teased fiber preparations, paraffin sections, and through immunohistochemistry. This case illustrates the presentation of this rare type of tumor, and characteristic neuroimaging and pathologic features of MPNSTs.
Isolated Mononeuropathy Multiplex—A Rare Manifestation of Intravascular Large B-Cell Lymphoma
Authors: Lynch Karen M. , Katz Joshua D. , Weinberg David H. , Lin Douglas I. , Folkerth Rebecca D. 
Published: August 2012

Abstract
Intravascular large B-cell lymphoma, also known as angiotrophic large cell lymphoma, is a rare disorder where neoplastic lymphoid cells proliferate within the walls of small- to medium-sized blood vessels. Peripheral neuropathy and other neurological manifestations, including stroke and dementia, are common, but cases of isolated multiple mononeuropathies in the absence of systemic symptoms are distinctly rare. We present an unusual case of biopsy-proved angiotrophic large cell lymphoma presenting exclusively with multiple mononeuropathies.
Romidepsin (FK228) and its analogs directly inhibit phosphatidylinositol 3‐kinase activity and potently induce apoptosis as histone deacetylase/phosphatidylinositol 3‐kinase dual inhibitors
Authors: Saijo Ken , Katoh Tadashi , Shimodaira Hideki , Oda Akifumi , Takahashi Ohgi , Ishioka Chikashi 
Published: August 2012

Activation of phosphatidylinositol 3‐kinase (PI3K) signaling is involved in carcinogenesis and cancer progression. The PI3K inhibitors are considered candidate drugs for cancer treatment. Here, we describe a drug screening system for novel PI3K inhibitors using Saccharomyces cerevisiae strains with deleterious mutations in the ATP‐binding cassette transporter genes, because wild‐type S. cerevisiae uses drug efflux pumps for reducing intracellular drug concentrations. By screening the chemical library of the Screening Committee of Anticancer Drugs, we identified the histone deacetylase (HDAC) inhibitor romidepsin (FK228) and its novel analogs. In vitro PI3K activity assays confirmed that these compounds directly inhibit PI3K activity at μM‐range concentrations. FK‐A5 analog was the most potent inhibitor. Western blotting revealed that these compounds inhibit phosphorylation of protein kinase B and downstream signaling components. Molecular modeling of the PI3K–FK228 complex indicated that FK228 binds to the ATP‐binding pocket of PI3K. At μM‐range concentrations, FK228 and FK‐A5 show potent cytotoxicity, inducing apoptosis even in HDAC inhibitor‐resistant cells. Furthermore, HDAC/PI3K dual inhibition by FK228 and FK‐A5 at μM‐range concentrations potentiates the apoptosis induction, mimicking the effect of combining specific HDAC and PI3K inhibitors. In this study, we showed that FK228 and its analogs directly inhibit PI3K activity and induce apoptosis at μM‐range concentrations, similar to HDAC/PI3K dual inhibition. In future, optimizing the potency of FK228 and its analogs against PI3K may contribute to the development of novel HDAC/PI3K dual inhibitors for cancer treatment.
Protein kinase A activation inhibits oncogenic Sonic hedgehog signalling and suppresses basal cell carcinoma of the skin
Authors: Makinodan Eri , Marneros Alexander G. 
Published: August 2012

AbstractBasal cell carcinoma of the skin (BCC) is caused by constitutive activation of the Sonic hedgehog (Shh) pathway, mainly through mutations either in the Shh receptor Patched (PTCH) or in its co‐receptor Smoothened (Smo). Inhibitors of this pathway that are currently in clinical trials inhibit Smo. However, mutations in Smo can result in resistance to these inhibitors. To target most BCCs and avoid acquired resistance because of Smo mutations, inhibiting the Shh‐pathway downstream of Smo is critical. Attractive downstream targets would be at the level of Gli proteins, the transcriptional activators of this pathway in BCCs. Previously it has been shown that Gli1 and Gli2, when phosphorylated by protein kinase A (PKA), are targeted for proteosomal degradation. Here we show that PKA activation via the cAMP agonist forskolin is sufficient to completely abolish oncogenic Smo activity in vitro. In an inducible BCC mouse model due to a Smo mutation that confers resistance to current Smo inhibitors, topical forskolin treatment significantly reduced Gli1 mRNA levels and resulted in strongly suppressed BCC tumor growth. Our data show that forskolin inhibits the growth of even those BCCs that are resistant to Smo inhibitors and provide a proof‐of‐principle framework for the development of topically applied human skin‐permeable novel pharmacologic inhibitors of oncogenic Shh‐signaling through PKA activation.
Altered levels of LXR‐α: crucial implications in the pathogenesis of vitiligo
Authors: Kumar Ravinder , Parsad Davinder , Kanwar Amrinderjit , Kaul Deepak 
Published: August 2012

AbstractIn recent times, the role of LXRs in skin physiology and pathology has evolved rapidly because of their role in proliferation, carcinogenesis, differentiation and permeability barrier function. LXRs were identified as promising drug targets for the treatment of many skin diseases. For this study, skin biopsies were taken from 15 patients with vitiligo and six controls to culture melanocytes from clinically active perilesional and normal skin. Gene expression was examined by reverse transcriptase–polymerase chain reaction analysis. Role of LXR‐α in regulating the expression of MMPs was checked by gene knock‐down, and its role in vitiligo pathogenesis was checked by treatment with LXR‐α agonist 22(R)‐hydroxycholesterol. After treatment adhesion assay, annexin V staining and proliferation assay were performed. The expression of LXR‐α was relatively more in perilesional skin melanocytes as compared to uninvolved skin melanocytes of non‐segmental vitiligo patient, and controls on the other hand, perilesional melanocytes were more prone to apoptosis. LXR‐α gene knock‐down significantly increases the expression of MMPs. LXR‐α agonist 22(R)‐hydroxycholesterol treatment significantly decreases melanocyte adhesion, apoptosis and proliferation. Higher expression of LXR‐α in perilesional skin melanocytes significantly decreases the adhesion, proliferation and matrix metalloproteinases and increases apoptosis.
Nestin and vimentin colocalization affects the subcellular location of glucocorticoid receptor in cutaneous melanoma
Authors: Lai Simone , Piras Franca , Spiga Saturnino , Perra Maria Teresa , Minerba Luigi , Piga Michela , Mura Ester , Murtas Daniela , Demurtas Paolo , Corrias Michela , Maxia Cristina , Ferreli Caterina , Sirigu Paola 
Published: August 2012

Aims:  Nestin (a neuronal stem cell/progenitor cell marker of central nervous system development), vimentin (which is ubiquitously expressed in mesenchymal cells), and the glucocorticoid receptor (GR, which is involved in the immune response, cell proliferation, and apoptosis) have been shown to interact in embryonic and undifferentiated tissues in modulating cell proliferation. The aim of this study was to analyse nestin, vimentin and GR expression in tumour tissue (melanoma), and their association with clinicopathological variables, to evaluate any effect on tumour progression.Methods and results:  Immunohistochemistry, double‐label immunofluorescence and confocal laser scanning microscopy were performed on biopsy specimens of cutaneous melanoma from 81 patients. Fisher’s and Pearson’s tests showed a correlation between nestin, vimentin and subcellular GR location (P = 0.008). Their concomitant expression also correlated with Clark level and thickness (P = 0.02 and P = 0.029, respectively). Kaplan–Meier analysis revealed a poorer outcome for stage III and IV patients with associated expression of nestin, vimentin and cytoplasmic GR in tumour tissue (P = 0.02).Conclusions:  These results suggest the presence in melanoma of growth mechanisms involving nestin, vimentin, and GR, similarly to that occurring in embryonic and undifferentiated cells, and may help in understanding tumour biology to provide a molecular basis for clinical therapies.
Defects in the vasoactive intestinal peptide (VIP)/VPAC system during early stages of the placental–maternal leucocyte interaction impair the maternal tolerogenic response
Authors: Fraccaroli L , Grasso E , Hauk V , Cortelezzi M , Calo G , Pérez Leirós C , Ramhorst R 
Published: August 2012

SummarySuccessful embryo implantation occurs followed by a local inflammatory/T helper type 1 (Th1) response, subsequently redirected towards a tolerogenic predominant profile. The lack of control of this initial local inflammatory response may be an underlying cause of early pregnancy complications as recurrent spontaneous abortions (RSA). Considering that vasoactive intestinal peptide (VIP) mediates anti-inflammatory and tolerogenic effects in several conditions we hypothesized that VIP might contribute to tolerance towards trophoblast antigens during the early interaction of maternal leucocytes and trophoblast cells. In this study we investigated VIP/VPAC system activity and expression on maternal peripheral blood mononuclear cells (PBMCs) after interaction with immortalized trophoblast cells (Swan-71 cell line) as an in-vitro model of feto–maternal interaction, and we analysed whether it modulates maternal regulatory T cell (Treg)/Th1 responses. We also investigated the contribution of the endogenous VIP/VPAC system to RSA pathogenesis. VIP decreased T-bet expression significantly, reduced monocyte chemotactic protein-1 (MCP-1) and nitrite production in co-cultures of PBMCs from fertile women with trophoblast cells; while it increased the frequency of CD4+CD25+ forkhead box protein 3 (Foxp3)+ cells, transforming growth factor (TGF)-β expression and interleukin (IL)-10 secretion. These effects were prevented by VIP-specific antagonist. Interestingly, PBMCs from RSA patients displayed significantly higher T-bet expression, lower Treg frequency and lower frequency of VIP-producer CD4 lymphocytes after the interaction with trophoblast cells. Moreover, the patients displayed a significantly lower frequency of endometrial CD4+VIP+ cells in comparison with fertile women. VIP showed a Th1-limiting and Treg-promoting response in vitro that would favour early pregnancy outcome. Because RSA patients displayed defects in the VIP/VPAC system, this neuropeptide could be a promising candidate for diagnostic biomarker or surrogate biomarker for recurrent spontaneous abortions.
Parental diet has strong transgenerational effects on offspring immunity
Authors: Triggs Alison M. , Knell Robert J. 
Published: August 2012

Summary
Transgenerational effects of immune stimulation on offspring immunity are widely reported from insects, but we know very little of how other aspects of the parental environment affect offspring immune reactivity.
We reared male and female moths Plodia interpunctella on either good‐ or poor‐quality food and then also raised their offspring on one of the two diet qualities. We found strong transgenerational effects on immunity: in general, if only one parent received the poor diet, reductions in immunity were observed whether that parent was the mother or the father, and the lowest offspring immune reactivity was observed when both parents received the poor diet.
The mechanism behind these effects is not known, but they could be caused either by imprinting, whereby the parent gives the offspring a cue such as an epigenetic mark that changes the offspring phenotype, or by the mother allocating fewer resources to their offspring when the diet was poor. Two lines of evidence point towards imprinting: the strong paternal effects and the observation that the size of these effects was either unchanged or increased when the offspring were fed a good‐quality diet themselves.
Weight was also reduced when either parent was fed a poor diet, except when both parents had a poor diet and the offspring were raised on good food, contrasting with the increased rates of obesity seen in vertebrates when either parent is raised on a restricted diet.
Overall, the effects of parental diet on offspring weight and immune reactivity are substantial and in some cases are equivalent to that of the diet that the offspring itself consumes.
Each life stage matters: the importance of assessing the response to climate change over the complete life cycle in butterflies
Authors: Radchuk Viktoriia , Turlure Camille , Schtickzelle Nicolas 
Published: August 2012

Summary

As ectothermic organisms, butterflies have widely been used as models to explore the predicted impacts of climate change. However, most studies explore only one life stage; to our best knowledge, none have integrated the impact of temperature on the vital rates of all life stages for a species of conservation concern.
Besides, most population viability analysis models for butterflies are based on yearly population growth rate, precluding the implementation and assessment of important climate change scenarios, where climate change occurs mainly, or differently, during some seasons.
Here, we used a combination of laboratory and field experiments to quantify the impact of temperature on all life stages of a vulnerable glacial relict butterfly. Next, we integrated these impacts into an overall population response using a deterministic periodic matrix model and explored the impact of several climate change scenarios.
Temperature positively affected egg, pre‐diapause larva and pupal survival, and the number of eggs laid by a female; only the survival of overwintering larva was negatively affected by an increase in temperature. Despite the positive impact of warming on many life stages, population viability was reduced under all scenarios, with predictions of much shorter times to extinction than under the baseline (current temperature situation) scenario. Indeed, model predictions were the most sensitive to changes in survival of overwintering larva, the only stage negatively affected by warming.
A proper consideration of every stage of the life cycle is important when designing conservation guidelines in the light of climate change. This is in line with the resource‐based habitat view, which explicitly refers to the habitat as a collection of resources needed for all life stages of the species. We, therefore, encourage adopting a resource‐based habitat view for population viability analysis and development of conservation guidelines for butterflies, and more generally, other organisms. Life stages that are cryptic or difficult to study should not be forsaken as they may be key determinants in the overall response to climate change, as we found with overwintering Boloria eunomia larvae.
Prenatal Diagnosis of X‐Linked Chronic Granulomatous Disease by Percutaneous Umbilical Blood Sampling
Authors: Sun J. , Wang Y. , Liu D. , Yu Y. , Wang J. , Ying W. , Wang X. 
Published: August 2012

AbstractIn this study, we investigated how to prenatally diagnose X‐linked chronic granulomatous disease (X‐CGD) effectively and accurately. Percutaneous umbilical blood sampling was conducted in the 22nd week of pregnancy. NADPH oxidase activity and gp91phox protein expression of neutrophils were analysed using flow cytometry. Direct sequencing was used to detect CYBB gene mutations. Umbilical blood was obtained from seven foetuses whose mothers were X‐CGD carriers. Six foetuses, whose mothers needed prenatal diagnosis because of other diseases, were used as control. The neutrophils in all 13 foetuses showed lower hydrogen peroxide generation (stimulation index < 100) and gp91phox protein expression. Among the seven foetuses whose mothers were X‐CGD carriers, four foetuses (Family 2, 4, 5 and 7) had CYBB gene mutations and showed very low hydrogen peroxide generation (stimulation index < 10) and no gp91phox expression. The other three foetuses (Family 1, 3 and 6) had no CYBB gene mutations and showed stimulation index of 20–50 and partial or normal gp91phox protein expression (no difference with controls). Two of the three mothers (Family 1 and 3) have delivered healthy infants with normal hydrogen peroxide generation and expression of gp91phox in neutrophils. Combined with direct sequencing, dihydrorhodamine oxidation analysis and gp91phox protein detection is an effective and accurate method for prenatal screening for X‐CGD.
Contrasting hypoxia tolerance and adaptation in Malus species is linked to differences in stomatal behavior and photosynthesis
Authors: Bai Tuanhui , Li Cuiying , Li Chao , Liang Dong , Ma Fengwang 
Published: August 2012

We examined the potential differences in tolerance to hypoxia by two species of apple rootstocks. Stomatal behavior and photosynthesis were compared between Malus sieversii and Malus hupehensis. Plants were hydroponically grown for 15 days in normoxic or hypoxic nutrient solutions. Those of M. sieversii showed much greater sensitivity, with exposure to hypoxia resulting in higher leaf concentrations of abscisic acid (ABA) that prompted stomatal closure. Compared with the control plants of that species, stomatal density was greater in both new and mature leaves under stress conditions. In contrast, stomatal density was significantly decreased in leaves from M. hupehensis, while stomatal length was unaffected. Under stress, the net photosynthetic rate, stomatal conductance and chlorophyll contents were markedly reduced in M. sieversii. The relatively hypoxia‐tolerant genotype M. hupehensis, however, showed only minor changes in net photosynthesis or chlorophyll content, and only a slight decrease in stomatal conductance due to such treatment. Therefore, we conclude that the more tolerant M. hupehensis utilizes a better protective mechanism for retaining higher photosynthetic capacity than does the hypoxia‐sensitive M. sieversii. Moreover, this contrast in tolerance and adaptation to stress is linked to differences in their stomatal behavior, photosynthetic capacity and possibly their patterns of native distribution.