On the reflex coactivation of ankle flexor and extensor muscles induced by a sudden drop of support surface during walking in humans.
Recent studies have revealed that the stretch reflex responses of both ankle flexor and extensor muscles are coaugmented in the early stance phase of human walking, suggesting that these coaugmented reflex responses contribute to secure foot stabilization around the heel strike. To test whether the reflex responses mediated by the stretch reflex pathway are actually induced in both the ankle flexor and extensor muscles when the supportive surface is suddenly destabilized, we investigated the electromyographic (EMG) responses induced after a sudden drop of the supportive surface at the early stance phase of human walking. While subjects walked on a walkway, the specially designed movable supportive surface was unexpectedly dropped 10 mm during the early stance phase. The results showed that short-latency reflex EMG responses after the impact of the drop (<50 ms) were consistently observed in both the ankle flexor and extensor muscles in the perturbed leg. Of particular interest was that a distinct response appeared in the tibialis anterior muscle, although this muscle showed little background EMG activity during the stance phase. These results indicated that the reflex activities in the ankle muscles certainly acted when the supportive surface was unexpectedly destabilized just after the heel strike during walking. These reflex responses were most probably mediated by the facilitated stretch reflex pathways of the ankle muscles at the early stance phase and were suggested to be relevant to secure stabilization around the ankle joint during human walking.


Blockade of LHRH-induced lordosis by alpha- and beta-adrenergic antagonists in ovariectomized, estrogen primed rats.
The participation of a noradrenergic mechanism in the facilitation of lordosis by luteinizing hormone-releasing hormone (LHRH) was studied in two groups of ovariectomized estrogen primed rats, with or without sexual experience. The administration of 5 micrograms estradiol benzoate (EB) alone to sexually inexperienced subjects (Ss) induced weak lordosis behavior in some of them (mean lordosis quotient, LQ = 12 +/- 19). The SC injection of 5 micrograms LHRH significantly increased this response four hours later (LQ = 38 +/- 41), though great variability was observed (59% of Ss showing LQs below 30). The systemic administration of either prazosin, an alpha-adrenergic antagonist (0.2 or 1 mg/kg), or propranolol, a beta-adrenergic antagonist (20 mg/kg), totally suppressed LHRH-induced lordosis in sexually inexperienced Ss (mean LQs = 8 +/- 11; 5 +/- 10; 18 +/- 31, respectively). In sexually experienced Ss (tested on two previous occasions with EB and LHRH) the administration of EB alone on a third test induced significant levels of lordosis (mean LQ = 51 +/- 41). The administration of 5 micrograms LHRH to sexually experienced, estrogen primed Ss induced near maximal levels of lordosis (LQ = 94 +/- 18). In these Ss, prazosin (0.2 and 1 mg/kg) and, to a lesser extent, propranolol (20 mg/kg) significantly depressed lordosis to values that were not significantly different from those obtained after EB alone (mean LQs = 59 +/- 38; 63 +/- 20; 74 +/- 32, respectively). These results indicate that blockade of noradrenergic transmission by either alpha- or beta-antagonists counteracts the stimulatory effect of LHRH on lordosis in ovariectomized estrogen primed rats with or without sexual experience.(ABSTRACT TRUNCATED AT 250 WORDS)


Design, synthesis and neuroprotective evaluation of nitrogen heterocyclic and triazole derivatives of sarracinic acid.
Novel sarracinic acid derivatives bearing triazole or N-heterocyclic moiety were prepared via two separate reaction schemes. The triazoles and the N-heterocyclic derivatives were synthesised using standard click chemistry approach and amination of 2-bromoethyl ester of sarracinic acid respectively. All the synthesised derivatives were screened for in vitro neuroprotective activity against corticosterone induced impairment in neuroblastoma cell line SH-SY5Y. Two analogs SA-2 and SA-12 exhibited strong neuroprotective activity. The cell viability, after high dose corticosterone induced cell death, increased remarkably with the pre treatment of SA-2 and SA-12. The in vitro biological activity of SA-2 and SA-12 was verified through docking studies. The docking studies were in good agreement with the biological results. SA-2 and SA-12 showed strong binding affinities with the target protein having ΔGb = -8.88 and -7.52; inhibition constant (ki) = 3.08 nM and 30.9 nM respectively.


Formation of a large rice body-containing cyst following total hip arthroplasty.
There are several well-described causes of a painful mass following total hip arthroplasty including polyethylene and metal wear debris, infection, expanding hematoma, dislocation, and synovial cysts. In addition to causing pain, these lesions, when large enough, may cause neurologic and vascular compromise. Rapid growth of the mass may clinically and radiographically resemble a sarcoma. Here, we report a case of a large painful hip mass which developed after total hip arthroplasty. The well-circumscribed mass was overlying and extending into the hip joint containing thousands of highly organized fibrin-containing "rice bodies". To our knowledge, this is the first report of a large, highly organized (rice-body-containing) cyst complicating total hip arthroplasty. A 55-year old Caucasian woman developed a large, slowly enlarging, painful hip mass 2 1/2 years after primary total hip arthroplasty. Clinically and radiographically, the lesion resembled a soft tissue sarcoma. Surgical removal identified a well-circumscribed mass extending into the hip joint containing thousands of highly organized fibrin-containing "rice bodies". Identification and excision of this "pseudotumor" following hip arthroplasty is important for obtaining a definitive diagnosis, ruling out malignancy or infection and relieving any potential compression on surrounding neurovascular structures.


Transplantation of placenta-derived multipotent cells in rats with dimethylhydrazine-induced colon cancer decreases survival rate.
Transplantation of placenta-derived multipotent cells (PDMCs) is a promising treatment method for many diseases. However, the impact of PDMCs on colon cancer has not yet been studied. PDMCs were obtained from rat placentas by culturing tissue explants. Colon cancer was experimentally induced in male albino Wistar rats by administering 20 mg/kg dimethylhydrazine (DMH) once a week for 20 consecutive weeks. The administration of the PDMCs was performed at the 20th week after the first DMH injection. The number and size of each tumour lesion were calculated in the 5th week after transplantation. The tumour type was determined by standard histological methods. To study the engraftment of PDMCs in the body of rats, the cells were transduced with enhanced green fluorescent protein. Cell engraftment was determined by assessing the presence of EGFP by PCR and immunohistochemistry. Survival of all rats was monitored daily. Allogeneic transplantation of PDMCs to rats at middle phase of DMH-induced colon carcinogenesis did not significantly influence the number of neoplasms and the parameters of mean and total tumour area, but led to an increase in size of the most invasiveness tumours. Intravenous allogeneic transplantation of PDMCs reduced the survival rate of rats with colon cancer by 17 days. PDMCs from rats engrafted into tissues of the normal intestine, tumours, lungs, liver, and spleen of rats for five weeks after intravenous transplantation. These results suggest that intravenous allogeneic transplantation of PDMCs promotes colon cancer progression and has a negative impact on survival of rats.


Tendon healing induced by chemically modified mRNAs.
Tendon disorders are frequent both in human and veterinary medicine with high re-injury rates and unsatisfactory therapeutic treatments. Application of naked, chemically-modified mRNA (cmRNA), encoding for therapeutic proteins, is an innovative approach to address tendon healing. In the current study, we demonstrated that injection of naked cmRNA, diluted in a glucose-containing solution, into tendons resulted in high protein expression in healthy and experimentally-injured tendons. Injection of bone morphogenetic protein 7 (BMP-7)-encoding cmRNA resulted in a significantly higher expression of BMP-7 protein and reduced formation of collagen type III, compared to vehicle control. Moreover, in a large animal model, reporter protein expression was detectable not only in healthy, but also in experimentally-injured, severely inflamed tendons. Summarising, these results demonstrated the potential of cmRNAs encoding for therapeutic proteins as a new class of drugs for the treatment of tendon disorders.


Predictive value of the combination of SMAD4 expression and lymphocyte infiltration in malignant transformation of oral leukoplakia.
Oral leukoplakia (OL) is a common, potentially malignant disorder of the oral cavity. SMAD4 was initially identified as a tumor suppressor and central mediator of transforming growth factor (TGF)-β signaling. In this study, we aimed to determine the expression patterns of SMAD4 in OL, its relationship with the degree of inflammation, and its clinical implications as a biomarker for OL malignant transformation. A total of 150 patients with OL were enrolled in this study. Paraffin-embedded sections obtained from biopsy or resection specimens were subjected to immunohistochemical analysis. Associations among the status of epithelial SMAD4 expression, stromal lymphocyte infiltration, and malignant transformation of OL were examined. Malignant transformation was significantly associated with the status of SMAD4 expression (P = 0.0017) and lymphocyte infiltration status (P = 0.0054). Cox regression analysis, based on the event-free survival (EFS), revealed that a low SMAD4 expression was a significant prognostic factor in OL patients (hazard ratio, 2.632; P = 0.043). In addition, a low SMAD4 expression was closely correlated with high lymphocyte infiltration (P = 0.00035), resulting in a significant correlation between the combination of low SMAD4 expression and high lymphocyte infiltration with malignant transformation of OL (P = 0.00027). The combination of the status of epithelial SMAD4 expression and stromal lymphocyte infiltration may be a useful biomarker for predicting malignant transformation in OL patients. These results suggest that not only epithelial SMAD4 loss, but also stromal features, may regulate the risk of malignant transformation of OL.


Second-line afatinib administration in an elderly patient with squamous cell carcinoma.
The majority of cases of lung cancer are still diagnosed at a late stage. At this stage, palliative therapeutic options including nonspecific cytotoxic drugs, targeted therapy, or immunotherapy can be utilized. In 2016, immunotherapy was approved in Europe for squamous cell carcinoma and adenocarcinoma. Moreover, afatinib was also approved as second-line therapy for squamous cell carcinoma. This article presents a case of a 76-year-old male with squamous cell carcinoma who received nab-paclitaxel as first-line therapy, and his treatment was switched to the tyrosine kinase inhibitor afatinib (40 mg) after disease progression with left lung atelectasis. After receiving afatinib for only 28 days, the atelectasis resolved. No adverse effects were observed from the afatinib therapy. In this case, afatinib 40 mg proved to be an effective alternative treatment for an elderly patient. Treatment choice should be based on the performance status of the patient, cost-effectiveness, and drug treatment guidelines.


Gene therapy of hematopoietic stem cells: strategies for improvement.
Gene therapy of hematopoietic stem cells (HSC) is limited by low frequency of the target cells, their quiescent nature, poor engraftment of treated HSC, and lack of a selective growth advantage of genetically modified cells. Lentiviral vectors combined with positive selection strategies using conditional cell-growth switches should allow for improvement.


Metaplastic breast carcinoma: Current therapeutic approaches and novel targeted therapies.
Metaplastic breast carcinoma (MBC) is a rare subtype of invasive breast cancer consisting of various combinations of malignant epithelial and mesenchymal cells. Its aggressive growth pattern combined with its histological heterogeneity account for MBC's characteristic resistance to systemic therapies, which subsequently leads to increased risk of recurrence and breast cancer mortality compared with other invasive mammary carcinomas. The aim of this review is to discuss the current therapeutic approaches, both in loco-regional as well as in systemic management of MBC. With the accumulation of knowledge from histopathologic assessment and the increasing identification of underlying molecular aberrations, emerging, novel targeted therapies will enable physicians to implement a more individualized and efficacious therapeutic strategy, leading hopefully to an improvement in the poor prognosis of MBC.


Mixed nitrogen/oxygen ligand affinities for bipositive metal ions and dioxygen binding to cobalt(II) complexes.
The complex formation of Co(II) and Cd(II) with mixed N/O ligands in dimethylsulfoxide (dmso) at 298 K is investigated by means of potentiometric, UV-Vis, calorimetric, FT-IR, NMR and electrochemical techniques. The linear and cyclic ligands investigated are: 2,2'-oxydiethylamine (NON), N-(2-hydroxyethyl)-ethylenediamine (NNO), 1,4,10-trioxa-7,13-diaza-cyclopentadecane (2,1) and 1,4,7,10-tetraoxa-13-azacyclopentadecane (2,2). The results are discussed by taking into account the donor strength of donor atoms, strain effects in the formation of chelate rings, steric and inductive effects and the size of the cavity when macrocyclic ligands are concerned. DFT studies are also performed to gain an insight into the stabilization of the lower oxidation state of the CoL2(2+/3+) couple in order to understand the different reactivity of the Co(II) complexes towards dioxygen. The kinetics of dioxygen uptake has been studied by UV-Vis measurements and the results reveal an interesting strong solvent effect, which is active in lowering the rate constant for formation of the initial superoxo complex.


TMEM230 Accumulation in Granulovacuolar Degeneration Bodies and Dystrophic Neurites of Alzheimer's Disease.
Transmembrane Protein 230 (TMEM230) is a newly identified protein associated with Parkinson's disease (PD) found in Lewy bodies and Lewy neurites of patients with PD or dementia with Lewy body disease. However, TMEM230 has not yet been investigated in the most common neurodegenerative disorder, Alzheimer's disease (AD). Here, we demonstrate that the expression of TMEM230 is specifically increased in neurons in AD patients. Importantly, both granulovacuolar degeneration (GVD) and dystrophic neurites (DNs), two prominent characteristic pathological structures associated with AD, contain TMEM230 aggregates. TMEM230 immunoreactivity can be detected in neurofibrillary tangles-containing neurons and hyperphosphorylated tau positive DNs. TMEM230 accumulation is also noted around senile plaques. These findings identifying TMEM230 as a component of GVD and DNs suggest TMEM230 dysregulation as a likely mechanism playing an important role in the pathogenesis of AD.


A database of life-history traits of European amphibians.
In the current context of climate change and landscape fragmentation, efficient conservation strategies require the explicit consideration of life history traits. This is particularly true for amphibians, which are highly threatened worldwide, composed by more than 7400 species, which is constitute one of the most species-rich vertebrate groups. The collection of information on life history traits is difficult due to the ecology of species and remoteness of their habitats. It is therefore not surprising that our knowledge is limited, and missing information on certain life history traits are common for in this species group. We compiled data on amphibian life history traits from literature in an extensive database with morphological and behavioral traits, habitat preferences and movement abilities for 86 European amphibian species (50 Anuran and 36 Urodela species). When it were available, we reported data for males, females, juveniles and tadpoles. Our database may serve as an important starting point for further analyses regarding amphibian conservation.


Capillary electrophoresis time-of-flight mass spectrometry for a confident elucidation of a glycopeptide map of recombinant human erythropoietin.
Capillary electrophoresis coupled to orthogonal accelerated time-of-flight mass spectrometry (CE/TOFMS) was used for the analysis of O- and N-glycopeptides of recombinant human erythropoietin (rhEPO). O(126) and N(83) with a tetraantennary complex type glycan (N(83)-4Ant) were selected as glycopeptide models to develop an optimum CE/TOFMS methodology capable of detecting and characterizing the wide variety of glycopeptides present in the glycoprotein digest. Glycopeptide adsorption in the inner surface of the fused-silica capillary was prevented after using a capillary conditioning of 1 M HAc between runs. On the other hand, different acidic conditions in the sheath liquid (SL) and in the background electrolyte (BGE) were tested with the aim of studying their influence in glycopeptide fragmentation. Finally, the fragmentor voltage value of the TOF-MS instrument was optimized to avoid the involuntary fragmentation of the native glycopeptides. Hence, the established method may be regarded as an excellent starting point to obtain reliable glycopeptide maps of complex glycoproteins such as rhEPO by CE/TOFMS.


Resistance to Leishmania major is linked to the H2 region on chromosome 17 and to chromosome 9.
In Leishmaniasis, as in many infectious diseases, clinical manifestations are determined by the interaction between the genetics of the host and of the parasite. Here we describe studies mapping two loci controlling resistance to murine cutaneous leishmaniasis. Mice infected with L. major show marked genetic differences in disease manifestations: BALB/c mice are susceptible, exhibiting enlarging lesions that progress to systemic disease and death, whereas C57BL/6 are resistant, developing small, self-healing lesions. F2 animals from a C57BL/6 X BALB/c cross showed a continuous distribution of lesion score. Quantitative trait loci (QTL) have been mapped after a non-parametric QTL analysis on a genome-wide scan on 199 animals. QTLs identified were confirmed in a second cross of 271 animals. Linkage was confirmed to a chromosome 9 locus (D9Mit67-D9Mit71) and to a region including the H2 locus on chromosome 17. These have been named Imr2 and Imr1, respectively.


[The preparation of bioglass/collagen/phosphoserine biomemetic composite scaffold and a study on its cytocompatibility].
In the present study, novel biomemetic composite scaffolds using the sol-gel derived bioactive glass (BG), collagen (COL), and phosphoserine (PS) were prepared by freeze-drying. MC3T3-E1 were cultivated in vitro, collected and seeded onto the surface of BG, BG-COL and BG-COL-PS. Cell attachment and proliferation were observed. The cell proliferation was tracked by MTT method 1,3,5 d after seeding. MTT showed that the cells can adhere to and proliferate well on the surface of the scaffolds, and the cell proliferation result of scaffold BG-COL-PS was better than those of scaffolds BG and BG-COL. Therefore, the scaffold BG-COL-PS can be a potential scaffold for tissue engineer.


[Respiratory effects of microinjection of three kinds of neurotransmitters in ventromedial region of nucleus facialis].
The effects of microinjection of three kinds of neurotransmitters in ventromedial region of nucleus facialis (VMNF) on respiration were observed in vagotomized, spontaneously breathing rabbits anesthetized with urethane. Microinjection of adrenaline in VMNF induced a marked increase in respiratory rate and amplitude of integrated phrenic activity associated with an increase in the initial rate of rise of inspiratory activity. However, alpha-receptor antagonist tolazoline elicited marked decreases in respiratory rate accompanied by little or no changes in amplitude of integrated phrenic activity and initial rate of rise of inspiratory activity. The respiratory effects of microinjection of adrenaline were blocked by previous injection of tolazoline. Microinjection of GABA and glycine resulted in a decrease of respiratory frequency. These results suggest that adrenaline, GABA and glycine may modulate respiration by acting on VMNF neurons as neurotransmitters.


Nordic Walking improves trunk stability and gait spatial-temporal characteristics in people with Parkinson disease.
This study aimed to assess the effect of walking with Nordic Walking (NW) poles on postural stability and gait spatial-temporal characteristics in individuals with PD and to determine the cognitive load associated operating the poles. Twelve individuals with PD (age: 61.6±11.7) were asked to perform four 90 s walking trials; with/without poles and with/without verbal fluency task (category fluency) after a 6-week independent NW training. We assessed gait spatial-temporal characteristics, and trunk postural stability using the APDM accelerometry system. Trunk frontal range of motion and peak velocity were smaller in NW compared to normal walking with and without the cognitive task (p < 0.01). Cadence, gait speed and stride length decreased in both pole conditions when performed with the cognitive task (p < 0.05). However stride length was longer with poles compared to without poles. The reduced range of motion and velocity of the trunk in the frontal plane of motion suggest that NW can improve postural stability independently of the addition of a cognitive task. Compared to normal walking, spatial-temporal characteristics did not further decline when the cognitive task was combined to NW. This suggests that NW is a suitable practice for gait rehabilitation protocols in PD.


A test of the master gene hypothesis for interspersed repetitive DNA sequences.
Many families of interspersed repetitive DNA elements, including human Alu and LINE (Long Interspersed Element) elements, have been proposed to have accumulated through repeated copying from a single source locus: the "master gene." The extent to which a master gene model is applicable has implications for the origin, evolution, and function of such sequences. One repetitive element family for which a convincing case for a master gene has been made is the rodent ID (identifier) elements. Here we devise a new test of the master gene model and use it to show that mouse ID element sequences are not compatible with a strict master gene model. We suggest that a single master gene is rarely, if ever, likely to be responsible for the accumulation of any repeat family.


Dystrophin gene transcripts skipping the mdx mutation.
The mdx mouse, an animal model used to study Duchenne muscular dystrophy, has a nonsense mutation in exon 23 of the dystrophin gene which should result in a truncated protein that cannot be correctly localized at the sarcolemma of the muscle fibers. Immunohistochemical staining with antidystrophin antibodies has shown that while most of the muscle tissue is dystrophin-negative, a small percentage of muscle fibers is clearly dystrophin-positive and has somehow bypassed the primary nonsense mutation. A sensitive nested polymerase chain reaction-based examination of dystrophin gene transcripts around the mdx mutation has revealed several alternatively processed transcripts. Four mRNA species skipped the mutation in exon 23, were in-frame, and could be translated into a shorter but still functional dystrophin protein. Specific tests for these transcripts demonstrated these were also present in normal mouse muscle tissue.


Dietary Practices in Saudi Cerebral Palsy Children.
To determine the dietary practices of Saudi cerebral palsy (CP) children. A self-administered questionnaire was used to collect the following information from parents of CP children: demographics, main source of dietary information, frequency of main meals, foods/drinks used for main meals and in-between-meals. Parents of 157 CP children participated. Parents were divided into three, while children were divided into two age groups. The main sources of dietary information included popular media (46.5%) and dentist (36.3%). Most of the children had three meals (71.3%) or two meals (24.8%) daily. Choices for main meals included meats (68.8%), vegetables (65.6%), fruits (28.4%) and puddings (38.9%). The main three drinks choices with main meals included packed juices (59.9%), bottled water (58.8%) and fresh fruit juices (33.1%). The choices for in-between meals snacks included biscuits (61.1%), potato chips (51.6%), fruits (43.9%) and chocolates (41.4%). The choice of drinks with snacks was similar to that used with main meals. In cross-tabulation, older parents used meat (p=.03) and soft drinks (p=.04) more often for their children's main meals. Older children were given meat (p=.004) and soft drinks (p=.04) more often with main meals. Older children were given potato chips as snacks more often than younger children (p=.02), and there was a trend towards use of chocolates as snacks in older children (p=.08). Parents of CP children need to be educated about dietary practices of their children especially in areas such as the use of packed juices, dairy products, soft drinks and chocolates.


Secretion of nerve growth factor from septum stimulates neurite outgrowth and release of the amyloid protein precursor of Alzheimer's disease from hippocampal explants.
Alzheimer's disease (AD) is characterized by the deposition of amyloid in the extracellular and intracellular compartments of the cerebral cortex. The extracellular amyloid consists of a protein (beta A4) which is derived from a larger precursor, the amyloid protein precursor (APP). Several studies have implicated APP in the regulation of neurite outgrowth during development, although the precise function of APP remains unknown. To examine the role of APP in the regulation of neurite outgrowth from hippocampal neurons, an explant culture system was developed. Explants of E18 mouse hippocampus were found to extend neurites when co-cultured with explants of E18 mouse septum. This finding demonstrated that the septum can release a neurite outgrowth-promoting factor (NOPF). As nerve growth factor (NGF) was also able to stimulate neurite outgrowth from the hippocampal explants, this suggested that the NOPF might be NGF. Immunoprecipitation of NGF from septal conditioned medium using a specific monoclonal antibody (27/21) completely blocked the neurite outgrowth-promoting effect, supporting this conclusion. Concomitant with its ability to stimulate neurite outgrowth, NGF stimulated the release of APP from the hippocampal explants. As previous studies have suggested that the binding of APP to heparan sulfate proteoglycans (HSPGs) in the extracellular matrix might be an important step in the regulation of neurite outgrowth by NGF, we examined the effect of APP on neurite outgrowth from dissociated hippocampal cells cultured on various protein substrates. When cells were cultured on a substrate of APP and HSPG, neurite outgrowth was markedly stimulated. No stimulation of neurite outgrowth was seen when neurons were cultured on substrates of either APP or HSPG alone. The results suggest that secreted forms of APP may be involved in stimulating neurite outgrowth from hippocampal neurons and that interactions between APP and HSPG may be important for a neurite outgrowth-promoting function.


Cementless Total Hip Arthroplasty Involving Trochanteric Osteotomy without Subtrochanteric Shortening for High Hip Dislocation.
Total hip arthroplasty with subtrochanteric shortening osteotomy is widely performed for high hip dislocation. However, suboptimal leg length discrepancy correction and nonunion of the osteotomy site remain concerns. Although total hip arthroplasty using trochanteric osteotomy without subtrochanteric osteotomy was introduced, cemented implants have been more commonly used than contemporary cementless implants in this procedure. We evaluated the long-term results of cementless total hip arthroplasty with trochanteric osteotomy without subtrochanteric osteotomy for high hip dislocation. From 1990 to 2002, 27 cementless total hip arthroplasties using trochanteric osteotomy without subtrochanteric osteotomy were performed in 26 patients with Crowe III or IV high hip dislocation and a mean age of 36.4 ± 12.9 years. Seven ceramic-on-ceramic, 8 ceramic-on-polyethylene, 10 metal-on-polyethylene, and 2 metal-on-metal bearings were inserted. Mean follow-up was 15.1 ± 3.7 years. We retrospectively reviewed medical records and radiographic data and evaluated the clinical and radiological results including the Harris hip score, implant survival, correction of leg length discrepancy, and occurrence of complications. The mean Harris hip score and leg length discrepancy improved significantly from 73.3 to 94.9 points and from 4.3 cm to 1.0 cm, respectively. With revision for loosening set as the end point, implant survival rates at 10 and 15 years postoperatively were 96.0% and 90.9% for stems and 74.1% and 52.3% for cups. In 8 of 10 hips with the metal-on-polyethylene bearing and 4 of 8 hips with the ceramic-on-polyethylene bearing, revision surgery was performed for aseptic loosening. However, no revision was performed in hips with the ceramic-on-ceramic bearing or the metal-on-metal bearing. Implant survival was significantly different by the type of bearing surface. Two permanent neurologic complications occurred in patients with a limb lengthening over 3.5 cm. With proper selection of the bearing surface coupled with adjustment of lengthening, cementless total hip arthroplasty using trochanteric osteotomy without subtrochanteric osteotomy might be a favorable treatment option for high hip dislocation.


Vitamin D replacement and type 2 diabetes mellitus.
The objective of this paper is to review the evidence testing the possible benefit of vitamin D replacement on diabetes control and complications. Type 2 diabetes mellitus (DM 2) has become a significant global health care problem and its reported incidence is increasing at an alarming rate. Despite the improvement in therapy and development of new drugs, treatment is still not optimal especially with the associated adverse effects of most of the available drugs. New efforts are shifted toward disease prevention and a search for safer drugs. New mounting evidence is associating low vitamin D to diabetes mellitus and as such many studies were conducted to test the effect of vitamin D replacement on incidence of diabetes, diabetes control as well as diabetes complications. Although these studies present several limitations, vitamin D replacement seems to have beneficial effect on all aspects of diabetes: incidence, control and complications. Further longer term and more powered controlled trials are necessary to draw firmer conclusions on this beneficial role of vitamin D treatment on DM.


Characterizing water circulation and contaminant transport in Lake Geneva using bacteriophage tracer experiments and limnological methods.
Multi-tracer tests with three types of marine bacteriophages (H4/4, H6/1, and H40/1), together with various limnological methods, including physicochemical depth profiling, surface drifters, deep current measurements, and fecal indicator bacteria analyses, have been applied to characterize water circulation and pathogen transport in the Bay of Vidy (Lake Geneva, Switzerland). The experimental program was carried out twice, first in November 2005, when the lake was stratified, and a second time during holomixis in February 2006. The bacteriophages were injected at three points at different depths, where contaminated waters enter the lake, including the outlet pipe of a wastewater treatment plant, a river, and a stormwater outlet. Thereafter, water samples were collected in the lake at 2 m depth during a 48 h sampling campaign. The results demonstrate that (i) contaminated river water spreads rapidly in the bay; (ii) a well-developed thermocline is highly effective in preventing contamination from the depth to rise up to the surface; (iii) rapid vertical mixing and pathogen transport occur under thermally homogeneous conditions; and (iv) repeated multi-tracertests with bacteriophages are a powerful technique to assess water circulation and contaminant transport in lakes where high dilution occurs.


Enhancement in Seed Priming-Induced Starch Degradation of Rice Seed Under Chilling Stress via GA-Mediated α-Amylase Expression.
Chilling stress is the major abiotic stress that severely limited the seedling establishment of direct-seeded rice in temperate and sub-tropical rice production regions. While seed priming is an efficient pre-sowing seed treatment in enhancing crop establishment under abiotic stress. Our previous research has identified two seed priming treatments, selenium priming (Se) and salicylic priming (SA) that effectively improved the seed germination and seedling growth of rice under chilling stress. To further explore how seed priming enhance the starch degradation of rice seeds under chilling stress, the present study evaluated the effects of Se and SA priming on germination and seedling growth, α-amylase activity, total soluble sugar content, hormone content and associated gene relative expression under chilling stress. The results showed that both Se and SA priming significantly increased the seed germination and seedling growth attributes, and enhanced the starch degradation ability by increasing α-amylase activity and total soluble sugar content under chilling stress. Meanwhile, seed priming increased the transcription level of OsRamy1A, OsRamy3B that regulated by GA, and increased the transcription level of OsRamy3E that regulated by sugar signals. Furthermore, seed priming significantly improved the GA3 contents in rice seeds by up-regulating the expression of OsGA3ox1 and OsGA20ox1, and decreased the ABA content and the expression of OsNCED1, indicating that the improved starch degradation ability in primed rice seeds under chilling stress might be attributed to the increased GA3 and decreased ABA levels in primed rice seeds, which induced the expression of GA-mediated α-amylase. However, studies to explore how seed priming mediate hormonal metabolism and the expression of OsRamy3E are desperately needed.


Pharmacological exploitation of indole-3-carbinol to develop potent antitumor agents.
The antitumor activity of indole-3-carbinol is attributable to its ability to interfere with multiple oncogenic signaling pathways governing cell cycle progression, survival, invasion, and other aggressive phenotypes of cancer cells, especially those mediated by EGFR/Src, Akt, NF-kB, endoplasmic reticulum stress, and nuclear receptors. This broad spectrum of antitumor activities in conjunction with its metabolic instability constitutes the rationale for the structural modifications of indole-3-carbinol and its metabolite diindoylmethane to develop novel classes of antitumor agents with improved potency and distinct mechanisms. Thus, this minireview focuses on the chemical biology of the lead optimization of these indole derivatives.


Genetic mapping of maize streak virus resistance from the Mascarene source. I. Resistance in line D211 and stability against different virus clones.
Maize streak virus (MSV) disease may cause significant grain yield reductions in maize in Africa. Réunion island maize germplasm is a proven source of strong resistance. Its genetic control was investigated using 123 RFLP markers in an F(2) population of D211 (resistant) × B73 (susceptible). This population of 165 F(2:3) families was carefully evaluated in Harare (Zimbabwe) and in Réunion. Artificial infestation was done with viruliferous leafhoppers. Each plant was rated weekly six times after infestation on a 1-9 scale previously adjusted by image analysis. QTL analyses were conducted for each scoring date, and for the areas under the disease, incidence and severity progress curves. The composite interval mapping method used allowed the estimation of the additive and dominance effects and QTL × environment interactions. Heritabilities ranged from 73% to 98%, increasing with time after infestation. Resistance to streak virus in D211 was provided by one region on chromosome 1, with a major effect, and four other regions on chromosomes 2, 3 (two regions) and 10, with moderate or minor effects. Overall, they explained 48-62% of the phenotypic variation for the different variables. On chromosome 3, one of the two regions seemed to be more involved in early resistance, whereas the second was detected at the latest scoring date. Other QTLs were found to be stable over time and across environments. Mild QTL × environment interactions were detected. Global gene action appeared to be partially dominant, in favor of resistance, except at the earliest scoring dates, where it was additive. From this population, 32 families were chosen, representing the whole range of susceptibility to MSV. They were tested in Réunion against three MSV clones, along with a co-inoculation of two of them. Virulence differences between clones were significant. There were genotype × clone interactions, and these were more marked for disease incidence than for severity. Although these interactions were not significant for the mean disease scores, it is suggested that breeders should select for completely resistant genotypes.


Optimizing CSP1 analogs for modulating quorum sensing in Streptococcus pneumoniae with bulky, hydrophobic nonproteogenic amino acid substitutions.
The prompt appearance of multiantibiotic-resistant bacteria necessitates finding alternative treatments that can attenuate bacterial infections while minimizing the rate of antibiotic resistance development. Streptococcus pneumoniae, a notorious human pathogen, is responsible for severe antibiotic-resistant infections. Its pathogenicity is influenced by a cell-density communication system, termed quorum sensing (QS). As a result, controlling QS through the development of peptide-based QS modulators may serve to attenuate pneumococcal infections. Herein, we set out to evaluate the impact of the introduction of bulkier, nonproteogenic side-chain residues on the hydrophobic binding face of CSP1 to optimize receptor-binding interactions in both of the S. pneumoniae specificity groups. Our results indicate that these substitutions optimize the peptide-protein binding interactions, yielding several pneumococcal QS modulators with high potency. Moreover, pharmacological evaluation of lead analogs revealed that the incorporation of nonproteogenic amino acids increased the peptides' half-life towards enzymatic degradation while remaining nontoxic. Overall, our data convey key considerations for SAR using nonproteogenic amino acids, which provide analogs with better pharmacological properties.


Antinuclear antibody testing - misunderstood or misbegotten?
Antinuclear antibodies (ANAs) are a diverse group of autoantibodies that recognize nuclear macromolecules and their complexes. ANAs represent key biomarkers in the evaluation of rheumatic diseases, most prominently systemic lupus erythematosus (SLE), and ANA testing is commonly performed in the clinical setting. In addition, ANA testing is now used to assess eligibility for participation in clinical trials of new therapeutic agents for SLE. ANAs can be assayed by various techniques, with the fluorescent ANA assay often viewed as the gold standard. Whereas a positive ANA test represents a classification criterion for SLE, up to 20-30% of the healthy population, depending on the assay used, is positive for an ANA, complicating the use of this test for diagnosis or the detection of preclinical autoimmunity. Furthermore, ANAs might be expressed in SLE less commonly than often thought. This Perspectives article discusses important questions about the use of ANA testing in both the clinical and research settings.


Leptin and Ob-Rb receptor isoform in the human digestive tract during fetal development.
Leptin, partially produced by the stomach, is a hormone involved in energy balance and regulation of food intake. It also regulates some digestive functions through its functional receptor Ob-Rb expressed by gastrointestinal epithelial cells. The objective of the study was to investigate the temporal and spatial appearance of Ob-Rb in the human digestive tract and leptin in the stomach. The esophagus, stomach, and intestine samples of 7- to 24-wk-old human fetuses and adult mucosae were studied by RT-PCR, immunohistochemistry, and Western blot. Leptin was measured by RIA in amniotic fluids at 16-33 wk gestation. All mucosae expressed Ob-Rb (mRNA and/or protein) between 7 and 9 wk gestation. Leptin protein appeared by 8 wk in the gastric mucosa, whereas leptin mRNA was detected around 11 wk. Leptin levels in amniotic fluids were significantly higher during the second than during the third trimester. Overall, Ob-Rb immunoreactivity was higher in young fetuses, during the period corresponding to the formation of gastric buds and primitive intestinal crypts and the beginning of differentiation of epithelial cell types, than in the oldest. Leptin added to culture medium of gastrointestinal explants from 10- to 12-wk-old fetuses appeared to affect DNA synthesis as compared with controls, indicating that leptin receptor functionality was developing. The strong expression of leptin, in amniotic fluid when fetuses begin swallowing then in the gastric mucosa, and the early presence of Ob-Rb in mucosae suggest a possible role for leptin, exerted endoluminally and in a paracrine pathway, in the developmental process (growth and/or maturation) of the human digestive tract.


Torture sequelae located to the skin.
Torture sequelae and associated diagnostic problems within the field of dermatology are reported. Patient 1 claimed to have been subjected to torture in 1973 in South America and reported that he had a thick rubber-like rope tied around each thigh just above the knees. Six years later a linear zone of alopecia was observed extending circularly around each thigh, probably representing cicatricial alopecia. Patient 2 claimed to have been subjected to torture in November 1978 in Iraq and reported that he was burned on several areas of the skin with a metal rod of the size and shape of a cigarette. One year later, several circular or serpiginous scars with a markedly atrophic centre and a narrow hypertrophic, distinctly demarcated peripheral zone were observed on the skin. They probably represent the sequelae to deep third-degree burns produced by an electrically heated, cylindrical metal rod. Patient 3 claimed to have been subjected to torture in July and August 1974 in India. She reported to have been burned on several areas of the skin with a cigar as well as lifted by her hair. A few days after the torture she developed transient features typical of traction alopecia in the scalp, including the appearance of pimples. The examination 6 years later revealed on the extremities two irregularly shaped and indistinctly demarcated scars, one of them slightly atrophic, which might be sequelae to burns produced by an ember from a cigar.


[Remarks on the hearing theory].
Many remarks have been presented on the present-day theory of hearing. Some mechanisms connected with transforming auditory information have been discussed. One's own opinions have been presented on the possibility of existence of proteins which change their conformation when influenced by the energy of the sound wave. The mechanism mentioned above resembles the one existing in the organs of sight, smell and taste.


Anterior cervical fusion with interbody cage containing beta-tricalcium phosphate: Clinical and radiological results.
Beta tricalcium phosphate (beta-TCP) is an osteoconductive, resorbable material. Its clinical effectiveness has been proved in many indications. This study was clinical and radiographic study report obtained in patients undergoing anterior cervical discectomy and fusion ACDF in which PEEK cages were filled beta-TCP in an injectable form. Between January 2010 and June 2011, 16 consecutive patients underwent ACDF using PEEK cages with beta-TCP. The cohort compromised 10 men and 6 women with a mean age of 45.2 years. The surgery was performed when the patient had myelopathy or radiculopathy with progressive neurological deficit, or failure of conservative treatment (a minimum of 3 months). The patients were evaluated by Odom criteria preoperatively and postoperative 3rd, 6th, 12th and 24th months. Preop and postop pain was evaluated with visual analogue scala (VAS). Disc height and fusion success rates were evaluated. Preoperative average VAS score was 7.9 (7-10) for neck pain and 8 (7-10) for arm pain. At the final follow-up, these scores became 1.5 and 1.4 for neck and arm pain, respectively. The average improvement rate was 81% for neck pain and 82.5% for arm pain. Postop ODOM's criteria main rate was 3.4. Bone fusion was achieved in 14 segments (70%) at 3rd month, 19 segments (95%) at 12th month follow-up assessment. Clinical and radiological results revealed that B-TCP is a good alternative synthetic fusion material for cervical interbody fusion. Level IV, therapeutic study.


Noninvasive embryo evaluation and selection by time-lapse monitoring vs. conventional morphologic assessment in women undergoing in vitro fertilization/intracytoplasmic sperm injection: a single-center randomized controlled study.
To determine whether time-lapse monitoring (TLM) for cleavage-stage embryo selection improves reproductive outcomes in comparison with conventional morphological assessment (CMA) selection. Prospective randomized controlled trial. Single academic center. We randomly assigned 139 women who were undergoing their first in vitro fertilization or intracytoplasmic sperm injection cycle to undergo either fresh embryo transfer or first frozen embryo transfer (FET). Only 1 cleavage-stage embryo was transferred to each participant. The patients were randomly assigned to either the CMA or the TLM group. In the CMA group, day 2 and day 3 embryos were observed. A good-quality cleavage-stage embryo was selected for transfer or freezing in both groups. The primary and secondary outcomes were the clinical pregnancy rate (CPR) and the live birth rate (LBR), respectively, after the first embryo transfer (fresh embryo transfer or FET). The CPR and LBR were significantly lower in the TLM group than in the CMA group (CPR: 49.18% vs. 70.42%; relative risk, 0.70; 95% confidence interval [CI], 0.52-0.94; LBR: 45.90% vs. 64.79%; relative risk, 0.71; 95% CI, 0.51-0.98). The CPR with fresh embryo transfer or FET did not significantly differ between the TLM and the CMA groups (fresh embryo transfer: 44.44% vs. 70.0%, relative risk, 0.63, 95% CI, 0.39-1.03; FET: 52.94% vs. 70.73%, relative risk, 0.75, 95% CI, 0.52-1.09). There was a significant difference in the LBR with fresh embryo transfer between the TLM and the CMA groups (40.74% vs. 66.67%; relative risk, 0.61; 95% CI, 0.36-1.03). The LBRs with FET were similar in the TLM and the CMA groups (50.0% vs. 63.41%; relative risk, 0.79; 95% CI, 0.52-1.19). The rates of early spontaneous abortion and ectopic pregnancy did not differ between the TLM and the CMA groups. Elective single cleavage-stage embryo transfer with TLM-based selection did not have any advantages over CMA when day 2 and day 3 embryo morphology was combined in young women with a good ovarian reserve. Because of these results, we conclude that TLM remains an investigational procedure for in vitro fertilization practice. ChiCTR1900021981.


Distinct microRNA expression in human airway cells of asthmatic donors identifies a novel asthma-associated gene.
Airway inflammation is a hallmark of asthma, and suggests a dysregulation of homeostatic mechanisms. MicroRNAs (miRNAs) are key regulators of gene expression necessary for the proper function of cellular processes. We tested the hypothesis that differences between healthy and asthmatic subjects may be a result of distinct miRNA cellular profiles that lead to differential regulation of inflammatory genes. We collected human bronchial epithelial cells from seven healthy donors and seven patients with asthma, and profiled miRNA expression, using the Affymetrix (Santa Clara, CA) miRNA array platform. Results were confirmed according to quantitative RT-PCR on RNA isolated from 16 healthy and 16 asthmatic donors. We identified 66 miRNAs that were significantly different (≥ 1.5-fold; P ≤ 0.05) between the two groups, and validated three of them in epithelial cells from 16 asthmatic and 16 healthy subjects. Molecular network analysis indicated that putative targets were principally involved in regulating the expression of inflammatory pathway genes (P ≤ 10(-4)). Our analysis confirmed the prediction that the expression of IL-8, Cox2, and TNF-α was up-regulated in asthmatic cells, whereas the expression of IL-6 was lower compared with that in healthy control subjects. Network analysis was also used to identify a novel asthma-associated gene. The top-ranked predicted target of the highly down-regulated miRNA-203 in asthmatic cells was the aquaporin gene AQP4. Its expression was confirmed to be significantly higher in cells from patients with asthma. Overall, these data suggest that the heightened inflammatory pathway activation observed in patients with asthma may be attributed to underlying aberrant miRNA expression.


Distribution and abundance of fish eggs and larvae in Arasalar estuary, Karaikkal, south-east coast of India.
The distribution and abundance of fish eggs and larvae have been studied at two Stations of Arasalar estuary. Eggs of Stolephorus sp., Mugil cephalus, Sardinella sp., Cynoglossus sp and the larvae of Stolephorus indicus, Ambassis commersoni, Terapon jarbua, Chanos chanos, Trichiurus sp Anguilla sp and Thryssa sp have been collected and identified. Environmental parameters such as temperature, salinity, pH and dissolved oxygen were also recorded. The present study clearly indicate the higher occurrence and abundant of fish eggs and larvae during March - July. The fair numbers of eggs and larvae indicate the existence of breeding ground within the estuary. Study on the physico-chemical parameters found that the abundance and distribution of fish eggs and larvae were influenced by the salinity of this estuary.


Switchable guest molecular dynamics in a perovskite-like coordination polymer toward sensitive thermoresponsive dielectric materials.
A new perovskite-like coordination polymer [(CH3)2NH2][Cd(N3)3] is reported which undergoes a reversible ferroelastic phase transition. This transition is due to varied modes of motion of the [(CH3)2NH2](+) guest accompanied by a synergistic deformation of the [Cd(N3)3](-) framework. The unusual two-staged switchable dielectric relaxation reveals the molecular dynamics of the polar cation guest, which are well controlled by the variable confined space of the host framework. As the material switches from the ferroelastic phase to the paraelastic phase, a remarkable increase of the rotational energy barrier is detected. As a result, upon heating at low temperature, this compound shows a notable change from a low to a high dielectric state in the ferroelastic phase. This thermoresponsive host-guest system may serve as a model compound for the development of sensitive thermoresponsive dielectric materials and may be key to understanding and modulating molecular/ionic dynamics of guest molecules in confined space.


The influence of acute normovolemic anemia on cerebral blood flow and oxygen consumption of anesthetized rats.
The influence of acute normovolemic anemia on cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRo2) was studied in normocapnic rats under nitrous oxide anaesthesia. The arterial hemoglobin content was reduced to values of about 12, 9, 6 and 3 g.(100 ml)(-1) by arterial bleeding and substitution with equal volumes of homolgous plasma. The CBF increased in proportion to the reduction in hemoglobin content to reach values of 500-600 per cent of normal at extreme degrees of anemia, but CMR02 remained unchanged. Cerebral venous PO2 and oxygen saturation did not decrease below normal values, indicating that tissue hypoxia did not develop. However, since the increase in CBF at hemoglobin concentrations of below 9 g(100 ml)(-1) was far in excess of that expected from the decrease in viscosity the results indicate thatdilatation of cerebral resistance vessels occurred. This dilatation, which was obviously related to the fall in arterial oxygen content, cannot be explained by any of the current theories proposed to explain cerebral hyperemia in hypoxia.


Selective IgA deficiency---some perspectives.
The clinical spectrum of IgA deficiency varies from good health to respiratory, gastrointestinal, autoimmune and malignant disorders. Evaluation of B lymphocytes with surface IgA receptors in this disease reveals cap formation, decreased to normal density of IgA receptors, and IgA secretion following pokeweed stimulation. Further study of antigen-induced B-lymphocyte phenomena is needed. The presence of decreased numbers of T-cell markers in some individuals with IgA deficiency suggests a T-"helper" cell defect.


A Multi-Center Study on the Relationship Between Developmental Regression and Disease Severity in Children With Autism Spectrum Disorders.
This study aimed to investigate the prevalence of developmental regression in children with Autism Spectrum Disorder (ASD) and to explore its relationship with disease severity. We finally included 1,027 ASD children aged 2-5 years from 13 cities in China: 138 with regressive ASD and 889 with non-regressive ASD. The Social Responsiveness Scale (SRS), Autism Behavior Checklist (ABC), Child Autism Rating Scale (CARS), and Children Neuropsychological and Behavioral Scale-Revision 2016 (CNBS-R2016) were used to evaluate the core symptoms and developmental status of children in the two groups. Among the 1,027 ASD children eventually included, 138 (13.44%) cases showed regressive behavior and the average regression occurring age was 24.00 (18.00-27.00) months. Among the regressive children, 105 cases (76.09%) had language regression, 79 cases (57.25%) had social regression, and 4 cases (2.90%) had motor regression. The total scores of ABC and the sub-score of sensory and stereotypic behavior (β = 5.122, 95% CI: 0.818, 9.426, P < 0.05; β = 1.104, 95% CI: 0.120, 2.089, P < 0.05; β = 1.388, 95% CI: 0.038, 2.737, P < 0.05), the SRS total scores and the sub-score of autistic mannerisms (β = 4.991, 95% CI: 0.494, 9.487, P < 0.05; β = 1.297, 95% CI: 0.140, 2.453, P < 0.05) of children in the regressive group were all higher than the non-regressive group. The total developmental quotient (DQ) of CNBS-R2016 and the DQ of gross motor, fine motor, adaptive behavior, language (β = -5.827, 95% CI: -11.529, -0.125, P < 0.05) and personal society in the regressive group were lower than the non-regressive group and the proportion of children with intelligent developmental impairment was higher the non-regressive group. Regressive autism is mainly manifested as language and social regression. Children with regressive ASD have more severe core symptoms, lower neurodevelopmental level DQ, and more serious disease degree than children with non-regressive ASD, which requires further etiological examinations and more clinical attention.


Depression and Immunity: the HCV model.
Available research shows that only some individuals will develop a specific psychiatric disorder in the presence of the same life events. Different regulation scales are used to define the events that can be considered as stressful and to value their psychological burden. A personal illness, especially if chronic, is certainly an event characterized by great emotional and psychological impact. Moreover, symptoms such as mood changes and anxiety, which are commonly observed in patients affected by HCV, can be related to the awareness of suffering from a chronic progressive disease and to the past or current substance abuse. It is well known that the assumption of interferon α (IFN α) is associated with the onset of depressive symptoms, similar to those observed in major depression, in fact, from 30% to 50% of patients receiving IFN develop depression during treatment.Many data in literature show the very important role of pro-inflammatory cytokines in the onset of the Depression.


A genomewide linkage study of preeclampsia/eclampsia reveals evidence for a candidate region on 4q.
Preeclampsia (PE) and eclampsia (E) are potentially life-threatening conditions that can occur during human pregnancy. Generally considered to be different degrees of severity of the same disease process, the PE/E syndrome is thought to be predominantly genetic in origin, although its exact etiology and genetics are not fully understood. Here we report results of a genomewide linkage search for the gene(s) responsible for susceptibility to PE/E, using 15 informative pedigrees and 90 polymorphic DNA markers from all autosomes. Because of uncertainties concerning inheritance and diagnosis, four different models that assume maternal gene expression have been used to carry out LOD-score analysis. The region between D4S450 and D4S610 (2.8 cM) on the long arm of chromosome 4 was identified as a strong candidate region for a PE/E-susceptibility locus. The maximum multipoint LOD score within this interval was 2.9. Analysis of markers in the region around D4S450 and D4S610 by the affected-pedigree-member method also supported the possibility of a susceptibility locus in this region. However, to verify or exclude definitively linkage to this region, other groups of PE/E pedigrees will be required.


Sarcoma of bone and soft tissue following treatment of Hodgkin's disease.
Intensive chemotherapy and radiotherapy of Hodgkin's Disease has resulted in improved survival rates. With long-term follow-up, however, a risk of secondary malignancy in these individuals is now appreciated. The authors of this report have encountered five patients who developed bone or soft tissue sarcomata more than 5 years after treatment of Hodgkin's Disease. The four males and one female ranged in age from 14 to 74 years at the time of diagnosis of Hodgkin's disease. Two had received radiotherapy alone for treatment of Hodgkin's disease, two were treated with radiation and chemotherapy, and one received only chemotherapy. The latent period prior to diagnosis of sarcoma ranged from 6 to 11 years. There was one case each of neurofibrosarcoma, fibrosarcoma, osteosarcoma, liposarcoma and leiomyosarcoma. Four patients died within 1 year of the diagnosis of sarcoma. One is alive with no evidence of disease 2 years following diagnosis and surgical excision of the sarcoma. On the basis of the Massachusetts General Hospital experience in the treatment of Hodgkin's Disease, the authors calculate a risk of 0.9% of sarcoma occurring in five year survivors of Hodgkin's disease. Previously reported cases of sarcoma following treatment of Hodgkin's disease are summarized. The pertinent literature is reviewed.


Spinal Muscular Atrophy.
This article provides a comprehensive overview of the diagnostic assessment and treatment of individuals with spinal muscular atrophy (SMA) due to homozygous deletions of SMN1 . In recent years, most states have incorporated SMA in their newborn screening panel. To provide the earliest diagnosis possible after symptom onset, vigilance is needed for births in states without newborn screening for SMA and when compound heterozygotes are missed by newborn screening programs. Supportive care for respiratory, nutritional, and orthopedic health impacts outcomes and is the cornerstone of care. Adaptive equipment, including assistive home technology, enables affected individuals to gain autonomy in their daily activities. Pharmacologic treatments approved by the US Food and Drug Administration (FDA) include three drugs that increase deficient survival motor neuron protein levels through SMN1 - or SMN2 - directed pathways: nusinersen, onasemnogene abeparvovec, and risdiplam. Efficacy for these trials was measured in event-free survival (survival without the need for permanent ventilation) and gains in functional motor outcomes. Earlier treatment is most effective across all treatments. The diagnostic and therapeutic landscapes for SMA have seen dramatic advancements in recent years, improving prognosis. Optimized supportive care remains essential, and vigilance is needed to define the new natural history of this disease.


[The shoe industry and the musculoskeletal system].
Shoes factory workers are engaged in ripetitive tasks, often performed in constrained postures and in concomitance of force applied, which result in increased risk of musculoskeletal disorders. Risk assessment and ergonomic interventions are part of the on-site prevention program, which should pertain also to gender and age differences. Health and safety issues can be adequately faced by an active epidemiological surveillance complemented by ergonomics.


Dynamic light scattering and circular dichroism studies on heat-induced gelation of hard-keratin protein aqueous solutions.
Animal hairs consist of aggregates of dead cells filled with keratin protein gel. We succeeded in preparing water-soluble hard-keratin proteins and reconstructing the keratin gels by heat-induced disulfide linkages in vitro. Here, the roles of intermolecular hydrophobic interaction and disulfide bonding between the proteins in the gel were discussed. Water-soluble keratin proteins consisting of mixtures of type I ( approximately 48 kDa) and type II ( approximately 61 kDa) were prepared from wool fibers as S-carboxymethyl alanyl disulfide keratin (CMADK). The gelation was achieved by heating an aqueous solution containing at least 0.8 wt % CMADK at 100 degrees C. CMADK solutions with different urea or N-ethylmaleimide concentrations or pH were exposed to dynamic light scattering (DLS) and circular dichroism (CD). DLS clarified the gelation point of CMADK solutions and provided information on the changes in keratin cluster size. DLS suggested two types of gelation mechanism. One was the regenerated chemical disulfide bonding between keratins from CMAD parts of chains. After the gel formed, this bond became important to maintain the gel structure. The other was the physical assembly due to hydrophobic interaction between alpha-helix parts of keratin chains. This hydrophobic assembly also played an important role during gelation. CD confirmed a conformational change in the keratin protein, resulting heat-induced gelation. CD clarified the relationship between keratin protein conformation and gelation, i.e., a rodlike conformation with many alpha-helix structures was necessary to associate keratin chains and form a gel network.


Galectin-1 interacts with beta-1 subunit of integrin.
Galectin-1, a beta-galactoside-binding dimeric lectin, is involved in adhesion, migration, and proliferation of vascular smooth muscle cells (SMC), the key steps in the development of atherosclerosis and restenosis. Here we investigated the molecular basis of the interactions between galectin-1 and SMCs. Galectin-1 modulated SMC attachment in a dose- and beta-galactoside-dependent manner. Direct binding of galectin-1 to beta1 integrin was detected by the immune precipitation of beta1 integrin after chemical cross-linking of 125I-labelled galectin-1 to the cell surface proteins. Galectin-1 transiently increased availability of beta1 integrins on the cell surface to antibodies against beta1 integrin. Incubation of SMCs with galectin-1 transiently increased the amount of the active form of beta1 integrin and tyrosine phosphorylation of two cytoskeleton-associated proteins; one of them coincided with focal adhesion kinase (FAK). Galectin-1 is likely to affect SMC adhesion by interacting with beta1 integrin on the cell surface of SMCs and inducing outside-in signalling.


Introduction to the Arizona Sky Island Arthropod Project (ASAP): Systematics, Biogeography, Ecology, and Population Genetics of Arthropods of the Madrean Sky Islands.
The Arizona Sky Island Arthropod Project (ASAP) is a new multi-disciplinary research program at the University of Arizona that combines systematics, biogeography, ecology, and population genetics to study origins and patterns of arthropod diversity along elevation gradients and among mountain ranges in the Madrean Sky Island Region. Arthropods represent taxonomically and ecologically diverse organisms that drive key ecosystem processes in this mountain archipelago. Using data from museum specimens and specimens we obtain during long-term collecting and monitoring programs, ASAP will document arthropod species across Arizona's Sky Islands to address a number of fundamental questions about arthropods of this region. Baseline data will be used to determine climatic boundaries for target species, which will then be integrated with climatological models to predict future changes in arthropod communities and distributions in the wake of rapid climate change. ASAP also makes use of the natural laboratory provided by the Sky Islands to investigate ecological and genetic factors that influence diversification and patterns of community assembly. Here, we introduce the project, outline overarching goals, and describe preliminary data from the first year of sampling ground-dwelling beetles and ants in the Santa Catalina Mountains.


Immunohistochemical Characterization of Fumarate Hydratase (FH) and Succinate Dehydrogenase (SDH) in Cutaneous Leiomyomas for Detection of Familial Cancer Syndromes.
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by germline mutations in the FH gene, and is associated with increased incidence of leiomyomas and a potentially aggressive variant of renal cell carcinoma (HLRCC-associated RCC). Absent immunohistochemical expression of fumarate hydratase (FH) has previously been used to diagnose HLRCC-associated RCC, but immunohistochemical staining of leiomyomas is not standard practice. We performed immunohistochemistry (IHC) on whole sections from consecutive cutaneous leiomyomas from our archives to evaluate for both FH and succinate dehydrogenase B expression, in addition to clinicopathologic data collection and review of all hematoxylin and eosin-stained slides for blinded morphologic evaluation of features reported to be seen in HLRCC-associated uterine leiomyomas. Ninety-six cutaneous leiomyomas from 87 patients were identified; 12 of these specimens were from 7 patients with documented HLRCC. FH expression by IHC was absent in 9 specimens and retained in 85 specimens; 2 cases were equivocal with minimal FH expression. Seven of the 9 absent expression specimens were from patients with HLRCC, as were both of the equivocal specimens. The overall sensitivity and specificity of absent FH expression in leiomyomas for detection of patients with HLRCC were 70.0% and 97.6%, respectively. Inclusion of cases classified as equivocal increased sensitivity to 75.0%. Succinate dehydrogenase B expression was retained in 95 specimens and equivocal in 1 specimen. None of the evaluated morphologic features showed any association with leiomyomas in HLRCC. Loss of FH immunohistochemical expression in cutaneous leiomyomas is a sensitive and specific marker for detection of HLRCC, thus suggesting a role for prospective FH IHC in patients with these tumors to screen for HLRCC.


Ethnic and Gender Considerations in the Use of Facial Injectables: African-American Patients.
The United States is becoming increasingly more diverse as the nonwhite population continues to rise faster than ever. By 2044, the US Census Bureau projects that greater than 50% of the US population will be of nonwhite descent. Ethnic patients are the quickest growing portion of the cosmetic procedures market, with African-Americans comprising 7.1% of the 22% of ethnic minorities who received cosmetic procedures in the United States in 2014. The cosmetic concerns and natural features of this ethnic population are unique and guided by differing structural and aging processes than their white counterparts. As people of color increasingly seek nonsurgical cosmetic procedures, dermatologists and cosmetic surgeons must become aware that the Westernized look does not necessarily constitute beauty in these diverse people. The use of specialized aesthetic approaches and understanding of cultural and ethnic-specific features are warranted in the treatment of these patients. This article will review the key principles to consider when treating African-American patients, including the average facial structure of African-Americans, the impact of their ethnicity on aging and structure of face, and soft-tissue augmentation strategies specific to African-American skin.


Quantification of magnetic nanoparticles with low frequency magnetic fields: compensating for relaxation effects.
Quantifying the number of nanoparticles present in tissue is central to many in vivo and in vitro applications. Magnetic nanoparticles can be detected with high sensitivity both in vivo and in vitro using the harmonics of their magnetization produced in a sinusoidal magnetic field. However, relaxation effects damp the magnetic harmonics rendering them of limited use in quantification. We show that an accurate measure of the number of nanoparticles can be made by correcting for relaxation effects. Correction for relaxation reduced errors of 50% for larger nanoparticles in high relaxation environments to 2%. The result is a method of nanoparticle quantification suitable for in vivo and in vitro applications including histopathology assays, quantitative imaging, drug delivery and thermal therapy preparation.


The concept of damage control: extending the paradigm to emergency general surgery.
A damage control (DC) approach was developed to improve survival in severely injured trauma patients. The role of DC in acute surgery (AS) patients who are critically ill, as a result of sepsis or overwhelming haemorrhage continues to evolve. The goal of this study was to assess morbidity and mortality of AS patients who underwent DC, and to compare observed and predicted morbidity and mortality as calculated from APACHE II and physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM) scores. Consecutive acute surgery patients who underwent DC from 2002 to 2004 were included. Retrospectively collected data included patient demographics, physiological parameters, surgical indications and procedures, mortality, morbidity, as well as volumes of crystalloid and colloid (plasma and red blood cell) resuscitation. Observed mortality and complications were compared to those calculated from APACHE II and POSSUM scores. Data were analysed using the Mann-Whitney test for median values, chi-square and Fisher's exact tests for proportions. Sixteen patients (mean age 53 years, seven men, nine women) underwent DC. The most common indications for DC included abdominal sepsis (6/15), intraoperative bleeding (5/15), and bowel ischaemia (3/15). The mean intraoperative blood loss during the index procedure was 2060mL. There were 2.4 average procedures per patient. At the end of DC II (36.5h), mean infusion of crystalloid was 17L, packed red blood cells was 3.6L, and plasma was 3L. Eight of 16 patients required vasopressor administration during resuscitation. At 28 days, there were five unexpected survivors as predicted by POSSUM and three by APACHE II (observed mortality seven, predicted mortality by the two methods: 12 (P=0.074), and 10 (P=0.24), respectively). Five patients died prior to definitive abdominal closure. Split thickness skin grafting (4/16) and primary fascial closure (4/16) constituted the most common methods of abdominal closure. Surgical morbidity predicted by POSSUM (98%) and actual morbidity (100%) were similar. Although the morbidity and mortality of AS patients undergoing DC is high, the application of DC principles in this group may reduce mortality compared to that predicted by POSSUM or APACHE II. In order to adequately demonstrate this contention, large, multi-institutional studies of DC in AS patients need to be performed. The POSSUM score appears to accurately estimate the high morbidity in general surgery DC patients, and supports the importance of team management of these complex patients by acute care surgery specialists.


Cognitive and executive impairments in Parkinson's disease psychosis: a Bayesian meta-analysis.
Cognitive and executive deficits lead to worsening of quality of life and are a risk factor for developing dementia in people with Parkinson's disease (PD) with psychosis (PDP). However, which key cognitive domains are differentially affected in PDP compared with those without (PDnP), remains unclear. Here, we examined this using a Bayesian meta-analytical approach. Searches were conducted on PubMed, Web of Science, SCOPUS, Medline and PsycINFO. Hedges' g effect-size estimates were extracted from eligible studies as a measure of standard mean differences between PDP and PDnP participants. Meta-analyses were conducted separately for each cognitive domain and subdomain, we examined the effect of age, PD medications, PD duration and severity, depression and psychosis severity for all major domains with meta-regressions. Effect-size estimates suggest worse performance on all major domains (k=105 studies) in PDP compared with PDnP participants, with global cognition (k=103 studies, g=-0.57), processing speed (k=29 studies, g=-0.58), executive functions (k=33, g=-0.56), episodic memory (k=30 studies, g=-0.58) and perception (k=34 studies, g=-0.55) as the most likely affected domains. Age, depression and PD duration had moderating effects on task-related performance across most of the major nine domains. We report extensive deficits across nine domains as well as subdomains in PD psychosis, with global cognition, processing speed and executive functions as the most likely impaired. The presence of depression may influence task-related performance in PDP, alongside age and PD duration, but not dose of dopamine replacement treatments.


Targeting neuropilin-1 to inhibit VEGF signaling in cancer: Comparison of therapeutic approaches.
Angiogenesis (neovascularization) plays a crucial role in a variety of physiological and pathological conditions including cancer, cardiovascular disease, and wound healing. Vascular endothelial growth factor (VEGF) is a critical regulator of angiogenesis. Multiple VEGF receptors are expressed on endothelial cells, including signaling receptor tyrosine kinases (VEGFR1 and VEGFR2) and the nonsignaling co-receptor Neuropilin-1. Neuropilin-1 binds only the isoform of VEGF responsible for pathological angiogenesis (VEGF165), and is thus a potential target for inhibiting VEGF signaling. Using the first molecularly detailed computational model of VEGF and its receptors, we have shown previously that the VEGFR-Neuropilin interactions explain the observed differential effects of VEGF isoforms on VEGF signaling in vitro, and demonstrated potent VEGF inhibition by an antibody to Neuropilin-1 that does not block ligand binding but blocks subsequent receptor coupling. In the present study, we extend that computational model to simulation of in vivo VEGF transport and binding, and predict the in vivo efficacy of several Neuropilin-targeted therapies in inhibiting VEGF signaling: (a) blocking Neuropilin-1 expression; (b) blocking VEGF binding to Neuropilin-1; (c) blocking Neuropilin-VEGFR coupling. The model predicts that blockade of Neuropilin-VEGFR coupling is significantly more effective than other approaches in decreasing VEGF-VEGFR2 signaling. In addition, tumor types with different receptor expression levels respond differently to each of these treatments. In designing human therapeutics, the mechanism of attacking the target plays a significant role in the outcome: of the strategies tested here, drugs with similar properties to the Neuropilin-1 antibody are predicted to be most effective. The tumor type and the microenvironment of the target tissue are also significant in determining therapeutic efficacy of each of the treatments studied.


Time course of the MAPK and PI3-kinase response within 24 h of skeletal muscle overload.
Knowledge of the molecular mechanisms by which skeletal muscle hypertrophies in response to increased mechanical loading may lead to the discovery of novel treatment strategies for muscle wasting and frailty. To gain insight into potential early signaling mechanisms associated with skeletal muscle hypertrophy, the temporal pattern of mitogen-activated protein kinase (MAPK) phosphorylation and phosphatidylinositol 3-kinase (PI3-kinase) activity during the first 24 h of muscle overload was determined in the rat slow-twitch soleus and fast-twitch plantaris muscles after ablation of the gastrocnemius muscle. p38alpha MAPK phosphorylation was elevated for the entire 24-h overload period in both muscles. In contrast, Erk 2 and p54 JNK phosphorylation were transiently increased by overload, returning to the levels of sham-operated controls by 24 h. PI3-kinase activity was increased by muscle overload only at 12 h of overload and only in the plantaris muscle. In summary, sustained elevation of p38alpha MAPK phosphorylation occurred early in response to muscle overload, identifying this pathway as a potential candidate for mediating early hypertrophic signals in response to skeletal muscle overload.


Effect of Ion Rigidity on Physical Properties of Ionic Liquids Studied by Molecular Dynamics Simulation.
In this work, we have performed molecular dynamics (MD) simulations to compare the structural and dynamical properties of three ionic liquids (ILs), 1-ethyl-3-methyl-imidazolium tetrafluorborate ([EMI(+)][BF4(-)]), 1,1'-dimethyl-4,4'-bipyridinium bis(tetrafluorborate) ([VIO(2+)][BF4(-)]2), and 1,1'-dimethyl-4,4'-bipyridinium bis(trifluoromethylsulfonyl)imide (bistriflimide in short) ([VIO(2+)][Tf2N(-)]2), aiming to discover the influence of ion rigidity on the physical properties of ILs. [VIO(2+)] is more rigid than [EMI(+)], and [BF4(-)] is more rigid than [Tf2N(-)]. [VIO(2+)][BF4(-)]2 has an anion distribution different from the other two by the higher and sharper peaks in the cation-anion radial distribution functions, reflecting a close-packed local structure of anions around cations. [VIO(2+)][BF4(-)]2 and [VIO(2+)][Tf2N(-)]2 have similar dynamics much slower than [EMI(+)][BF4(-)], and [VIO(2+)][Tf2N(-)]2 shows a more isotropic molecular distribution than [VIO(2+)][BF4(-)]2 and [EMI(+)][BF4(-)]. Additionally, we have simulated two modified viologen-based ILs to reinforce our interpretations. We conclude from the above simulation results that the rigidity of anions influences the alignment of cations and that the rigidity of cations shows a large obstacle to their rotational capacity. Moreover, we have observed a slower diffusion of [VIO(2+)][BF4(-)]2 due to the electrostatic correlations, which stabilizes the ion-cage effect.


EGCG, GCG, TFDG, or TSA Inhibiting Melanin Synthesis by Downregulating MC1R Expression.
Without affecting cell viability, epigallocatechin gallate (EGCG), gallocatechin gallate (GCG), theaflavine-3,3'-digallate (TFDG), or theasinensin A (TSA) have been found to effectively reduce intracellular melanin content and tyrosinase (TYR) activity. However, studies on the anti-melanogenic mechanism of the above samples remain weak, and the activities of these samples in regulating melanogenesis at the molecular level lack comparison. Using B16F10 cells with the α-melanocyte-stimulating hormone (α-MSH) stimulation and without the α-MSH stimulation as models, the effects of EGCG, GCG, TFDG, or TSA on cell phenotypes and expression of key targets related to melanogenesis were studied. The results showed that α-MSH always promoted melanogenesis with or without adding the four samples. Meanwhile, the anti-melanogenic activities of the four samples were not affected by whether the α-MSH was added in the medium or not and the added time of the α-MSH. On this basis, the 100 µg/mL EGCG, GCG, TFDG, or TSA did not affect the TYR catalytic activity but inhibited melanin formation partly through downregulating the melanocortin 1 receptor (MC1R), microphthalmia-associated transcription factor (MITF), and the TYR family. The downregulation abilities of catechins on the TYR family and MITF expression were stronger than those of dimers at both the transcription and translation levels, while the ability of dimers to downregulate the MC1R expression was stronger than that of catechins at both the transcription and translation levels to some extent. The results of molecular docking showed that these four samples could stably bind to MC1R protein. Taken together, this study offered molecular mechanisms for the anti-melanogenic activity of the EGCG, GCG, TFDG, and TSA, as potential effective components against the UV-induced tanning reactions, and a key target (MC1R) was identified.


β-Catenin mediates the establishment and drug resistance of MLL leukemic stem cells.
Identification of molecular pathways essential for cancer stem cells is critical for understanding the underlying biology and designing effective cancer therapeutics. Here, we demonstrated that β-catenin was activated during development of MLL leukemic stem cells (LSCs). Suppression of β-catenin reversed LSCs to a pre-LSC-like stage and significantly reduced the growth of human MLL leukemic cells. Conditional deletion of β-catenin completely abolished the oncogenic potential of MLL-transformed cells. In addition, established MLL LSCs that have acquired resistance against GSK3 inhibitors could be resensitized by suppression of β-catenin expression. These results unveil previously unrecognized multifaceted functions of β-catenin in the establishment and drug-resistant properties of MLL stem cells, highlighting it as a potential therapeutic target for an important subset of AMLs.


Abnormalities in late positive components of event-related potentials may reflect a genetic predisposition to schizophrenia.
Event-related potentials (ERPs) were recorded at the Cz region during syllable discrimination tasks in siblings of schizophrenic probands. ERPs in these siblings were compared to those of normal controls and schizophrenics. Siblings, similar to normal controls, displayed an increase in amplitudes of N100 according to the allocation of their attention between two different channels (ears), Siblings different from normal controls, however, failed to demonstrate an augmentation of late positive components upon detection of target stimuli in the attended channel. Mean amplitudes of late positive components elicited by target stimuli in the attended channel for siblings were nearly equal to those of unmedicated schizophrenics, with these values in siblings being significantly smaller as compared to those of normal controls. Based on these results, it was concluded that abnormalities of late positive components in siblings may reflect a genetic predisposition to schizophrenia.


Copper(II) assembling with bis(2-pyridylcarbonyl)amidate and N,N'-2,2-phenylenebis(oxamate).
We herein present the synthesis and X-ray structures of five copper(II) complexes of formulae [Cu(bpca)(CF3SO3)(H2O)]·H2O (1), [Cu(bpca)(Phpr)(H2O)]·3/2H2O (2), {[Cu(bpca)]2[Cu(opba)(H2O)]}·H2O (3), {[Cu(bpca)]2(H2opba)}2·6H2O (4) and [Cu(bpca)(EtH2opba)]n (5), where bpca = bis(2-pyridylcarbonyl)amidate, Phpr = 3-phenylpropionate, CF3SO3(−) = triflate (anion of the trifluoromethanesulphonic acid), H4opba = N,N′-1,2-phenylenebis(oxamic acid), and EtH3opba = monoethyl ester derivative of the H4opba. 1 and 2 are mononuclear copper(II) complexes where the copper atom is five-coordinate in distorted square pyramidal surroundings with a tridentate bpca and a water molecule (1)/carboxylate oxygen (2) building the basal plane and a triflate oxygen (1)/water molecule (2) filling the apical position. 3 is a neutral tricopper(II) complex where the [Cu(opba)(H2O)]2− unit acts as a bis-bidentate ligand toward two peripheral [Cu(bpca)]+ fragments. The three crystallographically independent copper(II) ions in 3 are five-coordinate with two nitrogen and two oxygen atoms (inner copper atom)/three bpca-nitrogen and an oxamate oxygen (outer copper atom) building the basal plane plus a water molecule (inner copper)/an oxamate oxygen (outer copper) in the apical position (inner copper atom) of somewhat distorted square pyramidal surroundings. 4 is a centrosymmetric tetracopper(II) compound where four [Cu(bpca)]+ fragments are assembled by two H2opba2− groups adopting an unusual bidentate/bis-monodentate bridging mode. The two crystallographically independent copper(II) ions in 4 are also five-coordinate having the three bpca-nitrogens in basal positions, the other two sites of the distorted square pyramid being filled by two oxygens of either a bidentate oxamate (at one copper centre) or two bis-monodentate oxamates (at the other copper atom). 5 is a zigzag chain of [Cu(bpca)(H2O)]+ units which are connected through the EtH2opba− ligand adopting a bidentate/monodentate bridging mode across the monodeprotonated oxamate group. Each copper(II) ion in 5 is six-coordinate in an elongated octahedral CuN3O3 chromophore. The magnetic properties of 3–5 were investigated in the temperature range 1.9–300 K. 3 exhibits an intermediate intramolecular antiferromagnetic interaction [J = -65.8(2) cm(-1) with the Hamiltonian H = -J(S(Cu1)·S(Cu2) + S(Cu2)·S(Cu3))] which leads to a low-lying spin doublet at low temperatures. A weak antiferromagnetic coupling between the inner copper(II) ions occurs in 4 [J = -2.36(2) cm(-1), H = -JS1·S2)] and a very small intrachain antiferromagnetic interaction is observed in 5 [J = -0.17(1) cm(-1) with H = -J∑(i)S(i)·S(i+1)]. These values are analyzed by means of simple orbital symmetry considerations and compared with those previously reported for parent systems.


Achieving High Resolution Ion Mobility Separations Using Traveling Waves in Compact Multiturn Structures for Lossless Ion Manipulations.
We report on ion mobility (IM) separations achievable using traveling waves (TW) in a Structures for Lossless Ion Manipulations (SLIM) module having a 44 cm path length and 16 90° turns. The performance of the TW-SLIM module was evaluated for ion transmission and IM separations with different RF, TW parameters, and SLIM surface gaps in conjunction with mass spectrometry. In this work, TWs were created by the transient and dynamic application of DC potentials. The module demonstrated highly robust performance and, even with 16 closely spaced turns, achieving IM resolution performance and ion transmission comparable to a similar straight path module. We found an IM peak capacity of ∼31 and peak generation rate of 780 s(-1) for TW speeds of ∼80 m/s using the current multi-turn TW-SLIM module. The separations achieved for isomers of peptides and tetrasaccharides were found to be comparable to those from a ∼0.9-m drift tube-based IM-MS platform operated at the same pressure (4 Torr). The combined attributes of flexible design, low voltage requirements and lossless ion transmission through multiple turns for the present TW-SLIM module provides a basis for SLIM devices capable of achieving much greater IM resolution via greatly extended ion path lengths and using compact serpentine designs.


Genetic polymorphism in BIN1 rather than APOE is associated with poor recognition memory among men without dementia.
Although several genetic polymorphisms have been linked with the risk of Alzheimer's disease, less is known about their impact on cognitive performance among cognitively healthy individuals. Our aim was to investigate the association of the genetic variant, rs744373 in the bridging integrator 1 gene (BIN1), the strongest genetic risk factor for Alzheimer's disease after the APOE ε4 allele, with different cognitive domains among non-demented older men. Cognitive function was measured using the CogState Brief Battery, which assessed cognitive performance across four domains: psychomotor function, visual attention, recognition memory and working memory. Linear regression analysis revealed that individuals with the BIN1 risk allele performed poorly on the recognition memory task as compared to those without the risk allele. However, this was in contrast with the individuals who harboured the APOE ε4 risk allele as they displayed better performance on the recognition task in comparison to those without the ε4 risk allele. To the best of our knowledge, this is the first study that demonstrates genetic variation in BIN1 to be a better predictor of recognition memory than APOE, which remains the biggest genetic risk factor for Alzheimer's disease.


[Indoleamine 2,3-Dioxygenase Activity during I131-Radioisotope Therapy for Metastatic Thyroid Cancer].
We evaluated the clinical significance of indoleamine 2,3-dioxygenase (IDO) during I131-radioisotope therapy for metastatic thyroid cancer. The IDO activity can be measured by the tryptophan (Trp)/kynurenine (Kyn) ratio. Trp and Kyn were measured by using high performance liquid chromatography (HPLC). The serum Trp/Kyn levels of were lower in thyroid cancer patients with lung metastases than in patients without metastases. The IDO activity increased after the development of lung metastases from thyroid cancer. The IDO activity was correlated with the number of metastatic lesions during I131-radioisotope therapy. These results suggest that measurement of the Trp/Kyn ratio is useful in the evaluation of the immunological metastatic status during I131-radioisotope therapy.


Adsorption Behavior and Mechanism of Cesium Ions in Low-Concentration Brine Using Ammonium Molybdophosphate-Zirconium Phosphate on Polyurethane Sponge.
Salt lake brine originating from Qinghai, China has abundant cesium resources and huge total reserves. The inorganic ion exchangers ammonium molybdophosphate (AMP) and zirconium phosphate (ZrP) have the significant advantages of separating and extracting Cs+ as a special adsorbent. Nevertheless, their high solubility in water leads to a decrease in their ability to adsorb Cs+ in aqueous solutions, causing problems such as difficulty with using adsorbents alone and a difficult recovery. In this work, an environmentally friendly polyurethane sponge (PU sponge) with a large specific surface area is employed as an adsorbent carrier by physically impregnating dopamine-coated AMP and ZrP onto a PU sponge, respectively. The experiment found that under the same conditions, the AMP/PU sponge performs better than the ZrP/PU sponge for Cs+ adsorption. When the amount of adsorbent reaches 0.025 g, the adsorption capacity reaches saturation. The adsorption efficiency remains above 80% when the concentration of Cs+ is 5-35 mg/L. The kinetic calculations show that adsorption is spontaneous, feasible, and has a higher driving force at high temperatures. In addition, the power and mechanism of the interaction between adsorbent and adsorbent are explained using the density functional theory calculation. This efficient, stable, and selective Cs+ adsorbent provides design guidelines.


PEP-19 overexpression in human uterine leiomyoma.
Although uterine leiomyomas represent one of the most common neoplasms in adult women, their pathogenesis remains poorly understood. A cDNA microarray analysis was performed to search for candidate genes expressed to a greater degree in leiomyoma compared with matched myometrium. A total of 15 candidate genes was obtained; neuron-specific protein PEP-19 (Purkinje cell protein 4; PCP 4) exhibited a striking difference in expression between leiomyoma and myometrium. Although PEP-19 expression has been reported exclusively in the central nervous system, the present study demonstrated that PEP-19 is also expressed in other human organs, including prostate, kidney and uterus. To clarify the role of PEP-19 in the pathogenesis of leiomyomas, PEP-19 expression was investigated for a series of human leiomyoma, as well as normal myometrium and leiomyosarcoma. PEP-19 mRNA and protein expression were much stronger in leiomyomas compared with normal myometrium, suggesting that PEP-19 might be involved in leiomyoma pathogenesis.


Additive methane-mitigating effect between linseed oil and nitrate fed to cattle.
The objective of this study was to test the effect of linseed oil and nitrate fed alone or in combination on methane (CH4) emissions and diet digestibility in cows. The experiment was conducted as a 2 × 2 factorial design using 4 multiparous nonlactating Holstein cows (initial BW 656 ± 31 kg). Each experimental period lasted 5 wk, with measures performed in the final 3 wk (wk 3 to 5). Diets given on a DM basis were 1) control (CON; 50% natural grassland hay and 50% concentrate), 2) CON with 4% linseed oil (LIN), 3) CON with 3% calcium nitrate (NIT), and 4) CON with 4% linseed oil plus 3% calcium nitrate (LIN+NIT). Diets were offered twice daily and were formulated to deliver similar amounts (DM basis) of CP (12.2%), starch (25.5%), and NDF (39.5%). Feed offer was restricted to 90% of voluntary intake (12.4 kg DMI/d). Total tract digestibility and N balance were determined from total feces and urine collected separately for 6 d during wk 4. Daily CH4 emissions were quantified using open chambers for 4 d during wk 5. Rumen fermentation and microbial parameters were analyzed from samples taken before and 3 h after the morning feeding. Rumen concentrations of dissolved hydrogen (H2) were measured continuously up to 6 h after feeding using a H2 sensor. Compared with the CON diet linseed oil and nitrate decreased (P < 0.01) CH4 emissions (g/kg DMI) by 17 and 22%, respectively, when fed alone and by 32% when combined. The LIN diet reduced CH4 production throughout the day, increased (P = 0.02) propionate proportion, and decreased (P = 0.03) ruminal protozoa concentration compared with CON diet. The NIT diet strongly reduced CH4 production 3 h after feeding, with a simultaneous increase in rumen dissolved H2 concentration, suggesting that nitrate does not act only as an electron acceptor. As a combined effect, linseed plus nitrate also increased H2 concentrations in the rumen. Diets had no effect (P > 0.05) on total tract digestibility of nutrients, except linseed oil, which tended to reduce (P < 0.10) fiber digestibility. Nitrogen balance (% of N intake) was positive for all diets but retention was less (P = 0.03) with linseed oil. This study demonstrates an additive effect between nitrate and linseed oil for reducing methanogenesis in cows without altering diet digestibility.


A systematic review of cognition in homeless children and adolescents.
Objectives The cognitive function of homeless children and adolescents may be overlooked, albeit understandably, when societal interventions focus on their immediate housing needs. Nevertheless, homelessness might be hypothesized to carry many risks for the developing mind and brain. We wanted to discover whether this hypothesis had been tested previously. Design A systematic review to examine whether cognitive impairments were reported in homeless children and adolescents. Setting Objective, systematic review of standard databases, examined by key word searches. Participants Children and adolescents. Main outcome measures Formal assessments of cognition. Results We found that in spite of there being many homeless children in the world, fewer than 2000 have been assessed cognitively and reported in the literature. Yet when compared with those who are domiciled, these children tend to have lower intellectual functioning and decreased academic achievement. Furthermore, adolescents evince cognitive impairments in the contexts of drug, physical, and sexual abuse. Conclusions We suggest that cognitive and mental health screening be incorporated into those intervention programs deployed to facilitate societal reintegration of homeless children and adolescents.


Effects of Some Indigenous Plants of North Karnataka (India) on Cardiovascular and Glucose Regulatory Systems in Alloxan-Induced Diabetic Rats.
Kenaf (Hibiscus cannabinus Linn, Pundi), Chick pea (Cicer arietinum Linn, Chana) and Prickly lettuce (Lactuca scariola Linn, Hattaraki) leaves are a few of indigenous plants which are routinely consumed by the people of north Karnataka in the diet. Studies on these plants showed some potential anti-diabetic efficacies. To examine the effect of leaves extracts of Hibiscus cannabinus Linn, Cicer arietinum Linn and Lactuca scariola Linn on cardiovascular integrity, glucose homeostasis and oxygen sensing cell signaling mechanisms in alloxan induced diabetic rats. In vitro and in vivo tests on glucose regulatory systems and molecular markers such as - NOS3, HIF- 1α and VEGF were conducted in alloxan induced diabetic rats supplemented with all the three plant extracts. Electrophysiological analysis (HRV, LF: HF ratio, baroreflex sensitivity, BRS) and histopathogy of myocardial tissues and elastic artery were evaluated in diabetic rats treated with L. scariola linn. Out of these three plant extracts, Lactuca scariola Linn supplementation showed significant beneficial effects on glucose homeostasis and oxygen sensing cell signaling pathways in alloxaninduced diabetic rats. Furthermore, effects of sub chronic supplementation of Lactuca scariola Linn aqueous extracts showed significant improvement in sympatho-vagal balance in diabetic rats by increase of Heart Rate Variability (HRV) and regaining of Baroreflex Sensitivity (BRS). These results were also corroborated with myocardial and elastic artery histopathology of Lactuca scariola Linn supplemented diabetic rats. These findings indicate an adaptive pathway for glucose homeostasis, oxygen sensing cell signaling mechanisms and cardio protective actions in alloxan - induced diabetic rats supplemented with Lactuca scariola Linn extracts.