Facilitating new movement strategies: Equine assisted physiotherapy for children with cerebral palsy.
Equine Assisted Physiotherapy (EAPT) offers children with cerebral palsy (CP) opportunities for new movement experiences, and may influence movement qualities. Descriptions of how, and to what extent EAPT affects trunk control is missing. The aim of this study was to explore if, and how changes in trunk control and changes in other movement aspects were observable in children with CP during EAPT, and if potential changes in trunk control could be measured. A multiple case study with a mixed methods design was completed. Two children with CP, GMFCS grade 1, were observed using video during a period of six months, and tested with Trunk Impairment Scale modified Norwegian Version. Skilled physiotherapists analyzed the videos qualitatively, and triangulated recurring changes in movement with the results from the test. Riding bareback, improvements in trunk control were observed and measured. However, riding in a saddle led to reduced trunk control. Other observable movement changes were: from asymmetry to symmetry, adaptation to rhythm, mastery of riding skills, and reduced loss of postural control. Increased instances of adapting own movements in spontaneous dialogue with the horse, were observed. Instructions and feedback from the therapist influenced the dialogue with the horse both positively and negatively. This study describes in detail how balance and symmetry can be stimulated during EAPT in a body characterized by imbalance and asymmetry. During EAPT, the children gained the possibility to explore new movement qualities. Equipment and feedback influenced movement qualities.


Jejunal strangulation and incarceration associated with bilateral perineal hernias in a neutered male dog.
An 8-year-old 6.8-kg neutered male Dachshund was presented for evaluation of vomiting, diarrhea, anorexia, and swelling over the right perineal region. The dog had a history of a bilateral perineal herniorrhaphy and castration 14 months prior to presentation. Bilateral perineal hernias were confirmed by digital rectal examination. Abdominal ultrasonography confirmed the presence of intestine within the right hernia. Three days after admission to the hospital, the region of the right perineal hernia became painful, erythematous, and edematous. Computed tomography revealed jejunal incarceration within the right hernia with dilation of 1 jejunal segment that indicated intestinal obstruction. Abdominal exploratory surgery was performed, during which irreducible small intestinal incarceration was confirmed. Intra-abdominal jejunal resection and anastomosis was performed, and an approximately 13-cm-long section of the jejunum was resected. Bilateral perineal herniorrhaphies with internal obturator and superficial gluteal muscle transposition were performed. Six months after surgery, digital rectal examination of the dog revealed that the repair was intact. The dog had no perineal hernia-related clinical signs at the time of the recheck examination. For the dog of the present report, surgical management of small intestinal strangulation associated with a perineal hernia was successful. Although a portion of the small intestines can frequently be found within perineal hernias in dogs, perineal hernia-related small intestinal strangulation has not been previously described, to the authors' knowledge. Veterinarians and clients should be aware of this potential complication secondary to perineal hernia and be prepared to perform an abdominal surgical procedure to address small intestinal incarceration in affected dogs.


Comparing the Diagnostic Classification Accuracy of iTRAQ, Peak-Area, Spectral-Counting, and emPAI Methods for Relative Quantification in Expression Proteomics.
Diagnostic classification accuracy is critical in expression proteomics to ensure that as many true differences as possible are identified with acceptable false-positive rates. We present a comparison of the diagnostic accuracy of iTRAQ with three label-free methods, peak area, spectral counting, and emPAI, for relative quantification using a spiked proteome standard. We provide the first validation of emPAI for intersample relative quantification and find clear differences among the four quantification approaches that could be considered when designing an experiment. Spectral counting was observed to perform surprisingly well in all regards. Peak area performed best for smaller fold differences and was shown to be capable of discerning a 1.1-fold difference with acceptable specificity and sensitivity. The performance of iTRAQ was dramatically worse than the label-free methods with low abundance proteins. Using the iTRAQ data set for validation, we also demonstrate a novel iTRAQ analysis regime that avoids the use of ratios in significance testing and outperforms a common commercial alternative.


Methods to Reduce Forest Residue Volume after Timber Harvesting and Produce Black Carbon.
Forest restoration often includes thinning to reduce tree density and improve ecosystem processes and function while also reducing the risk of wildfire or insect and disease outbreaks. However, one drawback of these restoration treatments is that slash is often burned in piles that may damage the soil and require further restoration activities. Pile burning is currently used on many forest sites as the preferred method for residue disposal because piles can be burned at various times of the year and are usually more controlled than broadcast burns. In many cases, fire can be beneficial to site conditions and soil properties, but slash piles, with a large concentration of wood, needles, forest floor, and sometimes mineral soil, can cause long-term damage. We describe several alternative methods for reducing nonmerchantable forest residues that will help remove excess woody biomass, minimize detrimental soil impacts, and create charcoal for improving soil organic matter and carbon sequestration.


Mammalian mitochondrial extracts possess DNA end-binding activity.
Mammalian mitochondrial protein extracts possess DNA end-binding (DEB) activity. Protein binding to a 394 bp double-stranded DNA molecule was measured using an electrophoretic mobility shift assay. Mitochondrial DEB activity was highly specific for linear DNA. Inclusion of a vast excess of non-radioactive circular DNA did not disrupt binding to radioactive f394. In contrast, binding was abolished by the inclusion of linear competitor DNA. In mammals, nuclear DEB activity is due to Ku, a hetero-dimer composed of the Ku70 and Ku86 proteins. To determine whether mitochondrial DEB activity was also due to Ku, protein extracts were prepared from the Chinese hamster XR-V15B cell line, which lacks this protein. As anticipated, nuclear extracts prepared from these cells lacked DEB activity. In contrast, mitochondrial extracts prepared from these cells had wild-type levels of DEB activity, demonstrating that this latter activity is not a consequence of nuclear contamination. Although the nuclear and mitochondrial DEB activities are independent of each other, they are nevertheless closely related, since mitochondrial DEB activity was 'supershifted' by both anti-Ku70 and anti-Ku86 antisera. The nuclear DEB protein Ku plays an essential role in nuclear DNA double-strand break repair. The DEB activity described herein may therefore play a similar role in mitochondrial DNA repair.


Testing longitudinal associations between executive function and academic achievement.
Children with higher levels of executive function (EF) skills consistently demonstrate higher levels of academic achievement. Despite the consistency of these associations, fundamental questions remain about whether efforts to improve an individual child's EF skills result in corresponding improvements in his or her academic performance. In the absence of experimental evidence, developmentalists have used repeated measures designs to test the nature, magnitude, and direction of the associations between EF skills and academic achievement. In contrast to previous studies, this study described how between- and within-person associations between EF and achievement address different questions. Using data from a subsample of participants (N = 6,040) from the Early Childhood Longitudinal Study-Kindergarten, 2010-2011 (ECLS-K:2011) cohort, we estimated a series of latent growth curve models with structured residuals to test the between and within-person associations between 2 dimensions of EF (working memory, cognitive flexibility) and 2 domains of academic achievement (math, reading). Whereas between-person associations between EF and achievement were large (φ = .55-.91), the within-person associations were small (βs = -.10-.25). Within-person effects of earlier reading achievement on later EF skills was the most consistent finding. Results were unchanged when analyses were repeated using the subset of children who were eligible for free and reduced-price lunch, a proxy for low socioeconomic households. Results are discussed with respect to interest in improving EF skills as a means for facilitating school outcomes. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Diversity, migration routes, and worldwide population genetic structure of Lecanosticta acicola, the causal agent of brown spot needle blight.
Lecanosticta acicola is a pine needle pathogen causing brown spot needle blight that results in premature needle shedding with considerable damage described in North America, Europe, and Asia. Microsatellite and mating type markers were used to study the population genetics, migration history, and reproduction mode of the pathogen, based on a collection of 650 isolates from 27 countries and 26 hosts across the range of L. acicola. The presence of L. acicola in Georgia was confirmed in this study. Migration analyses indicate there have been several introduction events from North America into Europe. However, some of the source populations still appear to remain unknown. The populations in Croatia and western Asia appear to originate from genetically similar populations in North America. Intercontinental movement of the pathogen was reflected in an identical haplotype occurring on two continents, in North America (Canada) and Europe (Germany). Several shared haplotypes between European populations further suggests more local pathogen movement between countries. Moreover, migration analyses indicate that the populations in northern Europe originate from more established populations in central Europe. Overall, the highest genetic diversity was observed in south-eastern USA. In Europe, the highest diversity was observed in France, where the presence of both known pathogen lineages was recorded. Less than half of the observed populations contained mating types in equal proportions. Although there is evidence of some sexual reproduction taking place, the pathogen spreads predominantly asexually and through anthropogenic activity.


Transfer function approach to the experimental determination of mode transfer matrices.
An improved scheme for characterization of multimode fiber systems is investigated. Characterization with transfer matrices requires multiple measurements for each component. The transfer function approach herein investigated requires only a single launch measurement to be made on a component, which afterward can be described by as few as two numbers. Further, it is shown that this technique is considerably more accurate and repeatable than matrix approaches. A concatenation experiment is performed to demonstrate the efficacy of the new technique as well as to compare it with the more traditional transfer matrix approach.


Safety and efficacy of in vivo gene transfer into the porcine heart with replication-deficient, recombinant adenovirus vectors.
Gene transfer with replication-deficient recombinant adenovirus (Ad) vectors may provide a novel approach to the treatment of some cardiac disorders. The relative efficiency of intramyocardial vs intracoronary Ad vector injection in transducing myocardial cells remains to be determined. Further, Ad vectors are associated with localized inflammation, and this could be associated with clinically significant side-effects. Female minipigs underwent open chest surgery and the Ad vector AdCMV.NLS beta-gal was injected into the circumflex coronary artery (IC; 2 x 10(10) p.f.u.; n = 5) or the posterobasal wall of the left ventricle (i.m.; 5 x 10(9) p.f.u., n = 4; 2 x 10(10) p.f.u., n = 18). The minipigs were killed after 2-31 days and the hearts examined for evidence of beta-galactosidase activity. Minipigs underwent epicardial echocardiography immediately before, within 15 min following the i.m. injection of AdCMV.NLS beta-gal and again at the time of death. Blood samples for white blood cell count, alkaline phosphatase, total bilirubin, blood urea nitrogen, creatinine and electrolytes were obtained before i.m. and i.c. injection of the Ad vector and before death. Intramuscular injection of the Ad vector was more efficient than i.c. infusion in infecting cells in a localized area of the heart. Myocardial beta-gal activity peaked at 3-6 days after i.m. injection and returned to its control value within 1 month. Although inflammatory cells were present at the injection site, echocardiograms did not show any evidence of either segmental or global left ventricular dysfunction. No minipigs died and all blood tests remained within normal limits following either i.m. or i.c. exposure to the Ad vector. In summary, direct i.m. administration of replication-deficient, recombinant Ad vectors provides a safe and effective approach for short-term gene transfer into the heart of large mammals.


Acromegaly is associated with decreased skin transepidermal water loss and temperature, and increased skin pH and sebum secretion partially reversible after treatment.
Acromegaly is characterized by an acquired progressive somatic disfigurement, mainly involving the face and extremities, besides many other organ involvement. Wet and oily skin was described in acromegaly patients and it was attributed to hyperhidrosis and increased sebum production but this suggestion has not been evaluated with reliable methods. The aim of this study was to examine the skin parameters of patients with acromegaly using measurements of skin hydration, sebum content, transepidermal water loss, pH and temperature and particularly the effects of 12 months of treatment on these parameters. 52 patients with acromegaly and 24 healthy control subjects were included in this two blinded prospective study. Skin properties were measured on forehead and forearm by Corneometer CM825, Sebumeter SM810, Tewameter TM210 and Phmeter PH900 as non-invasive reliable measuring methods. Serum GH, IGF-1 and all measurements of skin properties on forehead and forearm were repeated at the end of the 3, and 6 months of therapy in 20 cases. Patients were treated with appropriate replacement therapy for deficient pituitary hormones. The sebum content and pH of the skin of acromegalic patients were significantly higher and transepidermal water loss and skin temperature were found to be significantly lower in acromegalic patients when compared to the control group both on forehead and forearm. GH and IGF-1 levels were positively correlated with sebum levels and negatively correlated with skin temperature on both forehead and forearm. The sebum levels of the patients were significantly decreased both on forehead and forearm at 3rd and 6th months of treatment. The present study demonstrated increased sebum secretion, decreased transepidermal water loss, alkali and hypothermic skin surface in patients with acromegaly by reliable methods for the first time. These data suggest that GH and/or IGF-I may have a modulatory role on several skin characteristics which can be at least partially reversible with treatment.


Molecular diagnosis methods in familial hypercholesterolemia.
Familial hypercholesterolemia (FH) is considered the genetic cause of coronary heart disease and ischemic stroke. FH is mainly an autosomal codominant pattern-based disorder and is primarily determined by point mutations within the low-density lipoprotein receptor, apolipoprotein B, and proprotein convertase subtilisin/kexin type 9 genes, causing increased low-density lipoprotein cholesterol levels in the serum of untreated individuals. The accumulation will eventually lead to atherosclerotic cardiovascular disease. Although clinical criteria comprising several prognosis scores, such as the Simon Broome, Dutch Lipid Clinic Network, Make Early Diagnosis to Prevent Early Death, and the recently proposed Montreal-FH-SCORE, are the conventional basis of diagnosing FH, the genetic diagnosis made by single nucleotide polymorphism genotyping, multiplex ligation-dependent probe amplification analysis, and sequencing (both Sanger and Next-Generation sequencing) offers unequivocal diagnosis. Given the heterogeneity of known mutations, the genetic diagnosis of FH is often difficult to establish, despite the growing evidence of the causative mutations, as well as the polygenic aspect of this pathology and the importance of cascade screening of the FH patient's healthy family members. This review article details different genetic techniques that can be used in FH identification when there is a clinical FH suspicion based on criteria comprised in prognosis scores, knowing that none of these are exhaustive in the diagnosis, yet they efficaciously overlap and complement each other for confirming the disease at the molecular level.


Proteomic approach for characterization of immunodominant membrane-associated 30- to 36-kiloDalton fraction antigens of Leishmania infantum promastigotes, reacting with sera from Mediterranean visceral leishmaniasis patients.
The aim of the present study was to identify and characterize proteins of a 30- to 36-kDa fraction of Leishmania infantum promastigote membranes previously shown to be an immunodominant antigen(s) in Mediterranean visceral leishmaniasis (MVL) and a consistent and reliable serological marker of this disease. By the first approach, Coomassie-stained protein bands (32- and 33-kDa fractions) that specifically reacted by immunoblotting with sera from MVL patients were excised from the gel and submitted to enzymatic digestion to generate peptides. Four peptides were sequenced, three of which were shown to be definitely associated with MVL-reactive antigens and ascribed to a mitochondrial integral ADP-ATP carrier protein from L. major, a putative NADH cytochrome b(5) reductase, and a putative mitochondrial carrier protein, respectively. The second approach combined two-dimensional gel electrophoresis of membrane antigens and mass spectrometry (liquid chromatography-mass spectrometry/mass spectrometry) by using a quadrupole time-of-flight analysis. Six immunoreactive spots that resolved within a molecular mass range of 30 to 36 kDa and a pH range of 6.7 to 7.4 corresponded to four Leishmania products. The sequences derived from two spots were ascribed to a beta subunit-like guanine nucleotide binding protein, known as the activated protein kinase C receptor homolog antigen LACK, and to a probable member of the aldehyde reductase family. One spot was identified as a probable ubiquinol-cytochrome c reductase (EC 184.108.40.206) Rieske iron-sulfur protein precursor. The remaining three spots were identified as truncated forms of elongation factor 1alpha. These antigens correspond to conserved proteins ubiquitously expressed in eukaryotic cells and represent potential candidates for the design of a reliable tool for the diagnosis of this disease.


[Effect of duokang jiasu on the cytotoxicity of peripheral blood mononuclear cells].
Duokang Jiasu, a biological reaction modifier widely used in cancer clinics, has been proved that its tumor suppression effect is based on the macrophage activity. The results of this study showed that monocytes treated with Duokang jiasu in vitro has much stronger cytotoxicity against allogenic tumor cells. Incubation of mononuclear cells with Duokang jiasu beforehand could promote both NK and ADCC activities.


Designed metal-organic π-clusters combining the aromaticity of the metal cluster and ligands for a third-order nonlinear optical response.
The pivotal role of clusters and aromaticity in chemistry is undeniable, but there remains a gap in systematically understanding the aromaticity of metal-organic clusters. Herein, this article presents a novel metal-organic π-cluster, melding both metal-organic chemistry and aromaticity, to guide the construction of structurally stable Os-organic π-clusters. An in-depth analysis of these clusters reveals their bonding attributes, π-electronic composition, and origins of aromaticity, thereby confirming their unique metal-organic π-cluster properties. Furthermore, the Os5 cluster exhibits a promising third-order nonlinear optical (NLO) response, attributable to its narrow band gap and uniform electron/hole distribution, suggesting its potential as an optical switching material. This research introduces a fresh perspective on clusters, centered on delocalization, and broadens the domain of aromaticity studies. It also presents a novel method for designing efficient third-order NLO materials through consideration of the structure-activity relationship.


Predicting Lymph Node Metastasis From Primary Cervical Squamous Cell Carcinoma Based on Deep Learning in Histopathologic Images.
We developed a deep learning framework to accurately predict the lymph node status of patients with cervical cancer based on hematoxylin and eosin-stained pathological sections of the primary tumor. In total, 1524 hematoxylin and eosin-stained whole slide images (WSIs) of primary cervical tumors from 564 patients were used in this retrospective, proof-of-concept study. Primary tumor sections (1161 WSIs) were obtained from 405 patients who underwent radical cervical cancer surgery at the Fudan University Shanghai Cancer Center (FUSCC) between 2008 and 2014; 165 and 240 patients were negative and positive for lymph node metastasis, respectively (including 166 with positive pelvic lymph nodes alone and 74 with positive pelvic and para-aortic lymph nodes). We constructed and trained a multi-instance deep convolutional neural network based on a multiscale attention mechanism, in which an internal independent test set (100 patients, 228 WSIs) from the FUSCC cohort and an external independent test set (159 patients, 363 WSIs) from the Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma cohort of the Cancer Genome Atlas program database were used to evaluate the predictive performance of the network. In predicting the occurrence of lymph node metastasis, our network achieved areas under the receiver operating characteristic curve of 0.87 in the cross-validation set, 0.84 in the internal independent test set of the FUSCC cohort, and 0.75 in the external test set of the Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma cohort of the Cancer Genome Atlas program. For patients with positive pelvic lymph node metastases, we retrained the network to predict whether they also had para-aortic lymph node metastases. Our network achieved areas under the receiver operating characteristic curve of 0.91 in the cross-validation set and 0.88 in the test set of the FUSCC cohort. Deep learning analysis based on pathological images of primary foci is very likely to provide new ideas for preoperatively assessing cervical cancer lymph node status; its true value must be validated with cervical biopsy specimens and large multicenter datasets.


The ubiquitin-proteasome and the mitochondria-associated apoptotic pathways are sequentially downregulated during recovery after immobilization-induced muscle atrophy.
Immobilization produces morphological, physiological, and biochemical alterations in skeletal muscle leading to muscle atrophy and long periods of recovery. Muscle atrophy during disuse results from an imbalance between protein synthesis and proteolysis but also between apoptosis and regeneration processes. This work aimed to characterize the mechanisms underlying muscle atrophy and recovery following immobilization by studying the regulation of the mitochondria-associated apoptotic and the ubiquitin-proteasome-dependent proteolytic pathways. Animals were subjected to hindlimb immobilization for 4-8 days (I4 to I8) and allowed to recover after cast removal for 10-40 days (R10 to R40). Soleus and gastrocnemius muscles atrophied from I4 to I8 to a greater extent than extensor digitorum longus and tibialis anterior muscles. Gastrocnemius muscle atrophy was first stabilized at R10 before being progressively reduced until R40. Polyubiquitinated proteins accumulated from I4, whereas the increased ubiquitination rates and chymotrypsin-like activity of the proteasome were detectable from I6 to I8. Apoptosome and caspase-3 or -9 activities increased at I6 and I8, respectively. The ubiquitin-proteasome-dependent pathway was normalized early when muscle stops to atrophy (R10). By contrast, the mitochondria-associated apoptotic pathway was first downregulated below basal levels when muscle started to recover at R15 and completely normalized at R20. Myf 5 protein levels decreased from I4 to I8 and were normalized at R10. Altogether, our results suggest a two-stage process in which the ubiquitin-proteasome pathway is rapidly up- and downregulated when muscle atrophies and recovers, respectively, whereas apoptotic processes may be involved in the late stages of atrophy and recovery.


Component(s) of Sendai virus that can induce interferon in mouse spleen cells.
To identify the active component of Sendai virus that induces interferon in mouse spleen cells, infectious and noninfectious viruses, envelope particles derived from them, and isolated hemagglutinin-neuraminidase (HN) glycoproteins were examined for interferon induction. The interaction between membranous structures containing Sendai virus HN glycoprotein and the receptors on the cell surface was shown to be sufficient for interferon induction in mouse spleen cells, suggesting that the actual inducer of interferon in mouse spleen cells is the HN glycoprotein of Sendai virus. When mouse spleen cells were stimulated in vitro with Sendai virus grown in eggs or LLC-MK2 cells or with membranous structures containing glycoproteins obtained from these viruses, interferon could be detected in the culture fluid. Furthermore, isolated HN glycoprotein per se could induce interferon in the cells. A linear correlation was found between the titer of interferon induced and the hemagglutinating activity of the membranous structure containing the HN glycoprotein. It was concluded from these findings that HN glycoprotein was the active component of Sendai virus responsible for interferon induction in mouse spleen cells and that viral RNA and F glycoprotein were not required. The results also showed that the interaction between HN glycoprotein and receptors on the cell surface triggered production of type I interferon (IFN-alpha and IFN-beta). Although when Sendai virus was incubated at 56 degrees C for 5 min it lost its hemolytic and hemagglutinating activities, it induced a considerable amount of interferon in the culture fluid of mouse spleen cells. The interferon-inducing ability of heat-inactivated virus could be absorbed with mouse spleen cells but not with sheep erythrocytes or mouse erythrocytes, indicating that the inactivated virus retained ability to bind to mouse lymphoid cells.


Low-Dose Cannabinoid Type 2 Receptor Agonist Attenuates Tolerance to Repeated Morphine Administration via Regulating μ-Opioid Receptor Expression in Walker 256 Tumor-Bearing Rats.
Morphine is widely used in patients with moderate and severe cancer pain, whereas the development of drug tolerance remains a major problem associated with opioid use. Previous studies have shown that cannabinoid type 2 (CB2) receptor agonists induce morphine analgesia, attenuate morphine tolerance in normal and neuropathic pain animals, induce transcription of the μ-opioid receptor (MOR) gene in Jurkat T cells, and increase morphine analgesia in cancer pain animals. However, no studies of the effects of CB2 receptor agonists on morphine tolerance in cancer pain have been performed. Therefore, we investigated the effect of repeated intrathecal (IT) injection of the low-dose CB2 receptor agonist AM1241 on the development of morphine tolerance in walker 256 tumor-bearing rats. We also tested the influence of the CB2 receptor agonist AM1241 on MOR protein and messenger ribonucleic acid (mRNA) expression in the rat spinal cord and dorsal root ganglia (DRG). Walker 256 cells were implanted into the plantar region of each rat's right hindpaw. Tumor-bearing rats received IT injection of the CB2 receptor agonist AM1241 or antagonist AM630 with or without morphine subcutaneously twice daily for 8 days. Rats receiving drug vehicle only served as the control group. Mechanical paw withdrawal threshold and thermal paw withdrawal latency were assessed by a von Frey test and hot plate test 30 minutes after drug administration every day. MOR protein and mRNA expression in the spinal cord and DRG were detected after the last day (day 8) of drug administration via Western blot and real-time reverse transcription polymerase chain reaction. The data were analyzed via analysis of variance followed by Student t test with Bonferroni correction for multiple comparisons. Repeated morphine treatments reduced the mechanical withdrawal threshold and thermal latency. Coadministration of a nonanalgetic dose of the CB2 receptor agonist AM1241 with morphine significantly inhibited the development of morphine tolerance and increased the MOR protein expression in the spinal cord and DRG and mRNA expression in the spinal cord in tumor-bearing rats. Our findings indicate that IT injection of a nonanalgetic dose of a CB2 receptor agonist increased the analgesia effect and alleviated tolerance to morphine in tumor-bearing rats, potentially by regulating MOR expression in the spinal cord and DRG. This receptor may be a new target for prevention of the development of opioid tolerance in cancer pain.


Invasive fungal infections in pediatric hematopoietic stem cell transplant patients.
Pediatric hematopoietic stem cell transplant (HSCT) recipients are at high risk of invasive fungal infections (IFIs). To characterize IFIs and changes in fungal organisms over time in pediatric HSCT patients, we performed a retrospective cohort study of all HSCTs performed in pediatric patients at UCLA between 1991 and 2006. In all, 318 patients underwent 324 HSCT transplants over the 15-year period and 69 unique fungal infections were identified in 47 transplant patients. The overall incidence of fungal infections in HSCT recipients was 14.5%, with predominant organisms including Candida species (51%) and Aspergillus species (26%), with Candida albicans accounting for 18.8% of all fungal species. The distribution of organisms over time demonstrated a strong trend towards an increase in rare molds in more recent years. The respiratory tract was the main site of infection (52.6%), with urine and blood also noted as significant sites. Of all deaths in the patients with IFIs, fungal-related mortality accounted for 67.6% of deaths. HSCT patients have a much higher risk of fungal infections with rarer organisms becoming more prevalent, a finding likely linked to evolving antifungal practices over time. This emphasizes the need for the development and implementation of improved diagnostic, prophylactic, and therapeutic strategies to improve patient survival.


Genomic signatures of inbreeding and mutation load in a threatened rattlesnake.
Theory predicts that threatened species living in small populations will experience high levels of inbreeding that will increase their genetic load, but recent work suggests that the impact of load may be minimized by purging resulting from long-term population bottlenecks. Empirical studies that examine this idea using genome-wide estimates of inbreeding and genetic load in threatened species are limited. Here we use individual genome resequencing data to compare levels of inbreeding, levels of genetic load (estimated as mutation load) and population history in threatened Eastern massasauga rattlesnakes (Sistrurus catenatus), which exist in small isolated populations, and closely related yet outbred Western massasauga rattlesnakes (Sistrurus tergeminus). In terms of inbreeding, S. catenatus genomes had a greater number of runs of homozygosity of varying sizes, indicating sustained inbreeding through repeated bottlenecks when compared to S. tergeminus. At the species level, outbred S. tergeminus had higher genome-wide levels of mutation load in the form of greater numbers of derived deleterious mutations compared to S. catenatus, presumably due to long-term purging of deleterious mutations in S. catenatus. In contrast, mutations that escaped species-level drift effects within S. catenatus populations were in general more frequent and more often found in homozygous genotypes than in S. tergeminus, suggesting a reduced efficiency of purifying selection in smaller S. catenatus populations for most mutations. Our results support an emerging idea that the historical demography of a threatened species has a significant impact on the type of genetic load present, which impacts implementation of conservation actions such as genetic rescue.


[Repair of the large hepatobiliary duct defect with pedicle flap graft of the gallbladder or jejunum].
Sixteen patients suffering from complicated hepatolithiasis and ductal stricture were treated with a special U-shaped double balloon drainage catheter designed by the authors, and pedicle flap graft of gallbladder or jejunum for repair of large hepatobiliary duct defect were introduced. The follow-up study for 9-25 months (average 13.6 months) showed that the short-term results were excellent in all cases. The material structure of the drainage, the clinical diagnostic criteria of the disorder, the procedure of the operation and the clinical observation were also discussed.


Co-Fe films: effect of Fe content on their properties.
The characterizations of Co-Fe films electrodeposited on Ti substrates under potentiostatic conditions were investigated as a function of the Fe content in the films. The compositional analysis was carried out by energy dispersive X-ray spectroscopy. Scanning electron microscopy used to analyze the surface morphology of the films revealed that the film surface became rather smooth with the increase of the Fe contents. X-ray diffraction patterns showed that the crystal structure changed depending on the Co:Fe ratio in the films. It was observed that the crystal structure converted from the predominant face-centered-cubic to the body-centered-cubic with increasing Fe content. All films showed anisotropic magnetic resistance, but their magnitudes decrease as the Fe content increases. Magnetic data obtained from by vibrating sample magnetometer revealed that the changes observed in the saturation magnetization and coercivity values may arise from the Fe content of the films. The different magnetic and magnetotransport properties may come from the structural differences caused by the Fe content.


Maintaining Safety and Planning for the Future.
Kevin is a 12-year-old boy with autism spectrum disorder, intellectual disability (nonverbal IQ scores in mid-40s), and attention-deficit/hyperactivity disorder who has been followed up by a developmental-behavioral pediatrician (DBP) and a child psychologist for medication and behavioral management since he was 4 years old. Kevin was placed in the care of his great-great-aunt shortly after he turned 2 years of age because of concerns of neglect. She is now his legal guardian.Kevin is predominately nonverbal but does use a few single words to make requests or label items. He attends a public school and receives full-time special education support. He has a personal care assistant (PCA) who provides in-home support 5 to 6 days/wk for 3 to 4 hours at a time. The PCA is working on toilet training, using a "clock-training" approach, and also takes Kevin outdoors to play or on short outings during her visits. In his free time, Kevin prefers to watch cooking shows on television.Over the past year, Kevin's behaviors have become more concerning. There have been several episodes of Kevin waking up during the early morning hours and going to the kitchen to "cook." After one of these episodes, his guardian was not aware that Kevin had woken up until the next morning when she found a concoction of corn starch, coffee grounds, cottage cheese, and powdered drink mix in the blender. Kevin had also woken up during the night and ventured out of the house into the back yard. His guardian had woken up immediately as the alarm system sounded when he opened the outer door from the house to the yard.A door alarm was added to Kevin's bedroom door so that his guardian would be alerted when he leaves his bedroom; however, the alarm is not used consistently because there are times when the alarm cannot be found at bedtime. Kevin's guardian was able to obtain a GPS device for him to wear on his shoe from the local police department. He wears this without resistance every day.Kevin's guardian is in her mid-70s, and she has had several health issues over the past 2 to 3 years. There are no other family members who are willing or able to care for Kevin if his guardian were no longer able to. The DBP and child psychologist have encouraged Kevin's guardian to explore long-term residential care options with the state agency that provides support for individuals with intellectual disabilities and with Kevin's insurance provider, but the guardian is very reluctant to do this. She fears that Kevin will be removed from her care or placed in a "home" where someone will "do bad things to him."What else would you recommend or actions would you take to support Kevin's guardian in ensuring Kevin's safety and planning for his future care?


Molecular correlates of cisplatin-based chemotherapy response in muscle invasive bladder cancer by integrated multi-omics analysis.
Overtreatment with cisplatin-based chemotherapy is a major issue in the management of muscle-invasive bladder cancer (MIBC), and currently none of the reported biomarkers for predicting response have been implemented in the clinic. Here we perform a comprehensive multi-omics analysis (genomics, transcriptomics, epigenomics and proteomics) of 300 MIBC patients treated with chemotherapy (neoadjuvant or first-line) to identify molecular changes associated with treatment response. DNA-based associations with response converge on genomic instability driven by a high number of chromosomal alterations, indels, signature 5 mutations and/or BRCA2 mutations. Expression data identifies the basal/squamous gene expression subtype to be associated with poor response. Immune cell infiltration and high PD-1 protein expression are associated with treatment response. Through integration of genomic and transcriptomic data, we demonstrate patient stratification to groups of low and high likelihood of cisplatin-based response. This could pave the way for future patient selection following validation in prospective clinical trials.


The expanding Pandora's toolbox of CD8+T cell: from transcriptional control to metabolic firing.
CD8+ T cells are the executor in adaptive immune response, especially in anti-tumor immunity. They are the subset immune cells that are of high plasticity and multifunction. Their development, differentiation, activation and metabolism are delicately regulated by multiple factors. Stimuli from the internal and external environment could remodel CD8+ T cells, and correspondingly they will also make adjustments to the microenvironmental changes. Here we describe the most updated progresses in CD8+ T biology from transcriptional regulation to metabolism mechanisms, and also their interactions with the microenvironment, especially in cancer and immunotherapy. The expanding landscape of CD8+ T cell biology and discovery of potential targets to regulate CD8+ T cells will provide new viewpoints for clinical immunotherapy.


Anticonnective tissue and other antitissue 'antibodies' in the sera of patients with coeliac disease compared with the findings in a mixed hospital population.
Serum IgG specificities directed against various components of basement membrane and reticulin have been described, and their incidence in 138 patients with coeliac disease has been compared with that in 110 hospital inpatients, 100 normal blood donors, and 1441 other patients. A wide variety of antitissue specificities were observed but only a few appeared to be of any significance. The 'antireticulin' specificities have been subdivided into different groups according to their distinctive histological staining patterns. Specificity directed primarily against endothelial basement membrane was found most frequently in the sera of patients with hiatus hernia (35%) or coeliac disease (22%). The same specificity was also observed in patients with myasthenia gravis and to a lesser extent in Crohn's disease and in a mixed group of patients with unspecified organic gastrointestinal disease. An epithelial basement membrane reactivity was found in patients with rheumatoid arthritis but only rarely in other conditions. Staining of perivascular connective tissue represented a third type of 'antireticulin' specificity. It was found only rarely, although in coeliac disease this reactivity was found more frequently in combination with other connective tissue specificities.


Contribution of NF-kappa B and Sp1 binding motifs to the replicative capacity of human immunodeficiency virus type 1: distinct patterns of viral growth are determined by T-cell types.
Starting with a replication-incompetent molecular clone of human immunodeficiency virus type 1, lacking all the NF-kappa B and Sp1 binding sites present in the native long terminal repeat (LTR), proviruses containing reconstructed LTRs with individual or combinations of NF-kappa B and Sp1 elements were generated and evaluated for their capacity to produce virus progeny following transfection-cocultivation. Virus stocks obtained from these experiments exhibited a continuum of replicative capacities in different human T-cell types depending on which element(s) was present in the LTR. For example, in experiments involving proviral clones with LTRs containing one or two NF-kappa B elements (and no Sp1 binding sites), a hierarchy of cellular permissivity to virus replication (peripheral blood lymphocytes = MT4 greater than H9 greater than CEM greater than Jurkat) was observed. Of note was the associated emergence of second-site LTR revertants which involved an alteration of the TATA box. These results suggest that the human immunodeficiency virus type 1 LTR possesses functional redundancy which ensures virus replication in different T-cell types and is capable of changing depending on the particular combination of transcriptional factors present.


Iterative normalization of cDNA microarray data.
This paper describes a new approach to normalizing microarray expression data. The novel feature is to unify the tasks of estimating normalization coefficients and identifying control gene set. Unification is realized by constructing a window function over the scatter plot defining the subset of constantly expressed genes and by affecting optimization using an iterative procedure. The structure of window function gates contributions to the control gene set used to estimate normalization coefficients. This window measures the consistency of the matched neighborhoods in the scatter plot and provides a means of rejecting control gene outliers. The recovery of normalizational regression and control gene selection are interleaved and are realized by applying coupled operations to the mean square error function. In this way, the two processes bootstrap one another. We evaluate the technique on real microarray data from breast cancer cell lines and complement the experiment with a data cluster visualization study.


Cohort profile: the Themba Lethu Clinical Cohort, Johannesburg, South Africa.
The Themba Lethu Clinical Cohort was established in 2004 to allow large patient-level analyses from a single HIV treatment site to evaluate National Treatment Guidelines, answer questions of national and international policy relevance and to combine an economic and epidemiologic focus on HIV research. The current objectives of the Themba Lethu Clinical Cohort analyses are to: (i) provide cohort-level information on the outcomes of HIV treatment; (ii) evaluate aspects of HIV care and treatment that have policy relevance; (iii) evaluate the cost and cost-effectiveness of different approaches to HIV care and treatment; and (iv) provide a platform for studies on improving HIV care and treatment. Since 2004, Themba Lethu Clinic has enrolled approximately 30,000 HIV-positive patients into its HIV care and treatment programme, over 21,000 of whom have received anti-retroviral therapy since being enrolled. Patients on treatment are typically seen at least every 3 months with laboratory monitoring every 6 months to 1 year. The data collected include demographics, clinical visit data, laboratory data, medication history and clinical diagnoses. Requests for collaborations on analyses can be submitted to our data centre.


Reproducibility of 19 F-MR ventilation imaging in healthy volunteers.
To assess the reproducibility of percentage ventilated lung volume (%VV) measurements in healthy volunteers acquired by fluorine (19 F)-MRI of inhaled perfluoropropane, implemented at two research sites. In this prospective, ethically approved study, 40 healthy participants were recruited (May 2018-June 2019) to one of two research sites. Participants underwent a single MRI scan session on a 3T scanner, involving periodic inhalation of a 79% perfluoropropane/21% oxygen gas mixture. Each gas inhalation session lasted about 30 seconds, consisting of three deep breaths of gas followed by a breath-hold. Four 19 F-MR ventilation images were acquired per participant, each separated by approximately 6 minutes. The value of %VV was determined by registering separately acquired 1 H images to ventilation images before semi-automated image segmentation, performed independently by two observers. Reproducibility of %VV measurements was assessed by components of variance, intraclass correlation coefficients, coefficients of variation (CoV), and the Dice similarity coefficient. The MRI scans were well tolerated throughout, with no adverse events. There was a high degree of consistency in %VV measurements for each participant (CoVobserver1 = 0.43%; CoVobserver2 = 0.63%), with overall precision of %VV measurements determined to be within ± 1.7% (95% confidence interval). Interobserver agreement in %VV measurements revealed a high mean Dice similarity coefficient (SD) of 0.97 (0.02), with only minor discrepancies between observers. We demonstrate good reproducibility of %VV measurements in a group of healthy participants using 19 F-MRI of inhaled perfluoropropane. Our methods have been successfully implemented across two different study sites, supporting the feasibility of performing larger multicenter clinical studies.


Reno Orthopaedic Trauma Fellowship business curriculum.
The Reno Orthopaedic Center (ROC) Trauma Fellowship business curriculum is designed to provide the fellow with a graduate level business practicum and research experience. The time commitments in a typical 12-month trauma fellowship are significant, rendering a traditional didactic master's in business administration difficult to complete during this short time. An organized, structured, practical business education can provide the trauma leaders of tomorrow with the knowledge and experience required to effectively navigate the convoluted and constantly changing healthcare system. The underlying principle throughout the curriculum is to provide the fellow with the practical knowledge to participate in cost-efficient improvements in healthcare delivery. Through the ROC Trauma Fellowship business curriculum, the fellow will learn that delivering healthcare in a manner that provides better outcomes for equal or lower costs is not only possible but a professional and ethical responsibility. However, instilling these values without providing actionable knowledge and programs would be insufficient and ineffective. For this reason, the core of the curriculum is based on individual teaching sessions with a wide array of hospital and private practice administrators. In addition, each section is equipped with a suggested reading list to maximize the learning experience. Upon completion of the curriculum, the fellow should be able to: (1) Participate in strategic planning at both the hospital and practice level based on analysis of financial and clinical data, (2) Understand the function of healthcare systems at both a macro and micro level, (3) Possess the knowledge and skills to be strong leaders and effective communicators in the business lexicon of healthcare, (4) Be a partner and innovator in the improvement of the delivery of orthopaedic services, (5) Combine scientific and strategic viewpoints to provide an evidence-based strategy for improving quality of care in a cost-efficient manner, (6) Understand the political, economic, and strategic basics of private practice orthopaedics.


Hepatic versus gallbladder bile composition: in vivo transport physiology of the gallbladder in rainbow trout.
Ion and water transport across the teleost Oncorhynchus mykiss gallbladder were studied in vivo by comparing flow and composition of hepatic bile, collected by chronic catheter, to volume and composition of terminally collected gallbladder bile. Differences in composition were comparable with those of other vertebrates, whereas bile flow (75 microl. kg(-1). h(-1)) was below values reported for endothermic vertebrates. The gallbladder concentrates bile acids five- to sevenfold and exhibits higher net Cl(-) than Na(+) transport in vivo, in contrast to the 1:1 transport ratio from gallbladders under saline/saline conditions. Transepithelial potential (TEP) in the presence of bile, at the apical surface, was -13 mV (bile side negative) but +1.5 mV in the presence of saline. Bile acid in the apical saline reversed the TEP, presumably by a Donnan effect. We propose that ion transport across the gallbladder in vivo involves backflux of Na(+) from blood to bile resulting in higher net Cl(-) than Na(+) flux. This Na(+) backflux is driven by a bile side negative TEP and low Na(+) activity in bile due to the complexing effects of bile acids.


Intra-articular celecoxib improves knee extension regardless of surgical release in a rabbit model of arthrofibrosis.
Outcomes of current operative treatments for arthrofibrosis after total knee arthroplasty (TKA) are not consistently positive or predictable. Pharmacological in vivo studies have focused mostly on prevention of arthrofibrosis. This study used a rabbit model to evaluate intra-articular (IA) effects of celecoxib in treating contracted knees alone, or in combination with capsular release. A total of 24 rabbits underwent contracture-forming surgery with knee immobilization followed by remobilization surgery at eight weeks. At remobilization, one cohort underwent capsular release (n = 12), while the other cohort did not (n = 12). Both groups were divided into two subcohorts (n = 6 each) - one receiving IA injections of celecoxib, and the other receiving injections of vehicle solution (injections every day for two weeks after remobilization). Passive extension angle (PEA) was assessed in live rabbits at 10, 16, and 24 weeks, and disarticulated limbs were analyzed for capsular stiffness at 24 weeks. IA celecoxib resulted in greater mean PEA at ten weeks (69.6° (SD 4.6) vs 45.2° (SD 9.6), p = 0.004), 16 weeks (109.8° (SD 24.2) vs 60.9° (SD10.9), p = 0.004), and 24 weeks (101.0° (SD 8.0) vs 66.3° (SD 5.8), p = 0.004). Capsular stiffness was significantly reduced with IA celecoxib (2.72 Newton per cm (N·cm)/° (SD 1.04), p = 0.008), capsular release (2.41 N·cm/° (SD 0.80), p = 0.008), and capsular release combined with IA celecoxib (3.56 N·cm/° (SD 0.99), p = 0.018) relative to IA vehicle (6.09 N·cm/° (SD 1.64)). IA injections of a celecoxib led to significant improvements in passive extension angles, with reduced capsular stiffness, when administered to rabbit knees with established experimental contracture. Celecoxib was superior to surgical release, and the combination of celecoxib and a surgical release did not provide any additional value. Cite this article: Bone Joint Res 2022;11(1):32-39.


Metastatic pancreatic tumors: what is the optimal treatment?
Although rare, metastases to the pancreas from other primary tumors are increasingly recognized in clinical practice, but the optimal treatment remains unclear. When a careful staging is performed and widespread disease is excluded, the indication of pancreatectomy may arise. This study was designated to review the published literature on the results of surgical treatment for the most common malignancies metastasizing to the pancreas. Analysis of the reports show that resection can be performed safely, but long term survival is substantially influenced by the tumor's biology. There are convincing evidences that pancreatic resection for metastasis from renal cell cancer may offer excellent results in term of prolonged survival, while for other type of cancer, pancreatic resection should be considered only a palliative procedure, with only anedoctical reported long-term survivors. So, comparison of the results of surgical and non-surgical management of metastatic tumors to the pancreas is very difficult to perform. There is a need of studies evaluating the role of chemotherapy in the neoadjuvant setting or the best sequential use of multimodality treatment (targeted therapy, radiotherapy, surgery, etc.). At the moment, pancreatic resection for metastasis should be reserved to patients in good health conditions, with isolated disease from renal cell cancer. For other types of tumor, surgery should be performed only in individual basis.


Compensatory contributions of HEXIM1 and HEXIM2 in maintaining the balance of active and inactive positive transcription elongation factor b complexes for control of transcription.
Human positive transcriptional elongation factor b (P-TEFb), consisting of a cyclin-dependent kinase 9-cyclin T heterodimer, stimulates general and disease-specific transcriptional elongation by phosphorylating RNA polymerase II. The HEXIM1 protein, aided by the 7SK snRNA, sequesters P-TEFb into an inactive 7SK.HEXIM1.P-TEFb small nuclear ribonucleic acid particle for inhibition of transcription and, consequently, cell proliferation. Here we show that, like HEXIM1, a highly homologous protein named HEXIM2 also possesses the ability to inactivate P-TEFb to suppress transcription through a 7SK-mediated interaction with P-TEFb. Furthermore, HEXIM1 and HEXIM2 can form stable homo- and hetero-oligomers (most likely dimers), which may nucleate the formation of the 7SK small nuclear ribonucleic acid particle. Despite their similar functions, HEXIM1 and HEXIM2 exhibit distinct expression patterns in various human tissues and established cell lines. In HEXIM1-knocked down cells, HEXIM2 can functionally and quantitatively compensate for the loss of HEXIM1 to maintain a constant level of the 7SK/HEXIM-bound P-TEFb. Our results demonstrate that there is a tightly regulated cellular process to maintain the balance between active and inactive P-TEFb complexes, which controls global transcription as well as cell growth and differentiation.


Mechanistic Translation of Melanoma Genetic Landscape in Enriched Pathways and Oncogenic Protein-Protein Interactions.
Malignant melanoma is a skin cancer originating from the oncogenic transformation of melanocytes located in the epidermal layers. Usually, the patient's prognosis depends on timing of disease detection and molecular and genetic profiling, which may all significantly influence mortality rates. Genetic analyses often detect somatic BRAF, NRAS and cKIT mutations, germline substitutions in CDKN2A, and alterations of the PI3K-AKT-PTEN pathway. A peculiar molecular future of melanoma is its high immunogenicity, making this tumor targetable by programmed cell death protein 1-specific antibodies. Ten formalin-fixed paraffin embedded samples derived from melanoma patients were subjected to next-generation sequencing (NGS) analysis using the FDA-approved FoundationOne CDx™ test. The molecular features of each case were then analyzed employing several in silico prediction tools. We analyzed the mutational landscape of patients with metastatic or relapsed cutaneous melanoma to define enriched pathways and protein-protein interactions. The analysis showed that both known genetic alterations and variants of unknown significance rely on redundant signaling converging on similar gene ontology biological processes. Complex informatics analyses of NGS-based genetic results identified pivotal signaling pathways that could provide additional targets for cancer treatment. Our data suggest an additional role for NGS in melanoma, as analysis of comprehensive genetic findings using innovative informatic tools may lengthen the list of druggable molecular targets that impact patient outcome.


Holographic lithography of periodic two- and three-dimensional microstructures in photoresist SU-8.
Micro-fabrication of periodic structures was performed by holographic lithography technique in SU-8 photoresist using a simple and versatile experimental arrangement based on a diffractive beam-splitter. High-fidelity two- and three-dimensional microstructures fabricated with sub-micrometric resolution in large areas of approximately 1 mm diameter. The structures are potentially usable as elements of micro-fluidic systems (e.g., Brownian ratchets), and templates for photonic crystal devices (e.g., mirrors, collimators, superprisms).


Chrysin Reduces Oxidative Stress but Does Not Affect Polyol Pathway in the Lenses of Type 1 Diabetic Rats.
Prolonged hyperglycemia is one of the main causes of reactive oxygen species and free radicals generation in diabetes which may affect various organs, including the eye. Oxidative damage to proteins and lipids in the eye lens could lead to cataract formation. To cope with oxidative stress, the endogenous antioxidative system may be supported by the supplementation of exogenous antioxidants. The aim of this study was to evaluate the effect of chrysin, a natural flavonoid, on oxidative stress and polyol pathway-related markers in the lenses of streptozotocin-induced type 1 male diabetic rats. Chrysin at doses of 50 and 100 mg/kg was administered by gavage for 28 days. This treatment resulted in a decrease in antioxidative enzymes activity and oxidative stress index. Moreover, chrysin administration elevated the reduced glutathione level in the lenses. A decrease in the markers linked to oxidative damage to proteins and lipids in the lenses was noted, especially after treatment with 50 mg/kg of chrysin. Neither of the chrysin doses affected glycemia-related markers in the serum or altered parameters related to the polyol pathway and advanced glycation end-products level in the lenses of diabetic rats. Upon obtaining results, it can be concluded that chrysin reveals antioxidative activity in the lenses but shows no antihyperglycemic or antiglycation properties.


Virologically confirmed population-based burden of hospitalization caused by respiratory syncytial virus, adenovirus, and parainfluenza viruses in children in Hong Kong.
To determine virologically confirmed hospitalization rates associated with respiratory syncytial virus (RSV), adenovirus, and parainfluenza viruses in Hong Kong children. All patients <18 years of age living on Hong Kong Island (within Hong Kong SAR) admitted for a febrile acute respiratory infection to 1 of the 2 public hospitals on 1 fixed day of the week between October 2003 and September 2006 were prospectively recruited. Hong Kong Island has a known population denominator and these 2 hospitals managed 72.5% of all general pediatric admissions for this population. Nasopharyngeal aspirates were tested for RSV, adenovirus, and parainfluenzae types 1, 2, and 3 by direct antigen detection and culture. The annual hospitalization rate for RSV in infants <6 months of age was 233.4 to 311.2 per 10,000. Parainfluenza type 3 had a hospitalization rate of 27.3 to 122.8 per 10,000 in the 1 to <2 years group. Adenovirus was associated with significant hospitalization in those 6 months to 1 year (25.9-77.8 per 10,000), and in those 2 to <5 years (38.1-59.2 per 10,000). The mean duration of hospitalization for RSV was 4.04 ± 2.61 days, significantly longer than the 3.12 ± 1.41 days for adenovirus and the 2.93 ± 2.54 days for parainfluenza infections (P = 0.013 and P = 0.038, respectively). We documented that the overall pediatric hospitalization burden of RSV was high and comparable to that of influenza. The burden for all the studied viruses was mainly in previously healthy children <5 years of age.


Misophonia: An Underrecognized Disease in Pediatric Patients.
Misophonia is a chronic condition in which patients experience a strong negative, emotional, or psychologic reaction to specific sounds. These sounds cause the individual to have a sudden, uncontrolled, and disproportionate negative reaction affecting their daily activities. The literature describes several cases of misophonia in the adult population; however, only 2 pediatric case studies are reported. Herein, we present 2 additional cases. An exaggerated response to an auditory stimulus is observed in other disorders such as tinnitus, hyperacusis, migraines, and many psychiatric disorders. Sound aversion has a broad differential diagnosis and may require visits to numerous specialists, placing strain on the patient and the healthcare system. Furthermore, misophonia is underdiagnosed in the pediatric population as it requires self-reporting of symptoms. The pathophysiology, prevalence, and treatment of misophonia continue to be relatively unknown. We attempt to highlight this rarely reported pediatric diagnosis and elaborate on its clinical presentation to increase awareness among otolaryngologists.


[Malignant duodenal neoplasia: clinical-pathological profile].
The main purpose of the study was to learn about the clinical-pathological profile of the malignant duodenal neoplasia in our country. To that effect, a descriptive and prospective study was performed, involving the examination of 25 cases diagnosed between April 2000 and March 2002 in the Department of Digestive System Diseases of the "Edgardo Rebagliati Martins" National Hospital (Lima-Peru). Malignant duodenal neoplasia accounted for 1.6% of malignant gastro-intestinal neoplasias, with 86.2% endoscopic - histologic correlation. The average age was 64.9 years, with predominance of males (64%). The average period of the symptoms until diagnosis was reached, was of 6.2 months, the most frequent being: weight loss (84%) paleness (84%) abdominal pain (64%) and hyporexia (60%). The obstructive picture prevailed in the inframpullary lesions, high digestive hemorrhage in the suprampullary lesions and obstructive jaundice in the periampullary lesions. Metastases was evident in 64.7% of primary malignant neoplasias. The most frequent type of lesion was mixed (40%) prevailing the proliferative-ulcerated type and most had a suprampullary location (44%). The most frequent histological variation was the adenocarcinoma (52%) followed by metastatic lesions (32%), lymphoma (12%) and carcinoid tumor (4%). The treatment administered was merely supportive in 14 cases (56%), palliative in seven cases (28%) and curative in three cases (12%). Global survival by the end of the six months was of 12.5%. Malignant duodenal neoplasia is an unusual incident, with delayed and non-specific clinical symptoms and it is therefore diagnosed in advanced stages. A curative treatment is seldom possible, hence global survival after six months is very low.


Antihypertensive pharmacology.
Although drug treatment of hypertension is associated with improved survival and decreased vascular complications, drug compliance is a major problem in the control of hypertension. All antihypertensive medications are associated with side effects; thus, it is a physician's responsibility to explain to each patient the side effects of the drugs he prescribes to treat hypertension, and to instill in the patient a sense of necessity for the treatment of hypertension. The choice of antihypertensive drug should be made based on each patient's lifestyle, overall health and ability to tolerate the drug. Ideally, the antihypertensive regimen should be simple, effective, convenient to take and have very few side effects.


Enhanced efflux of cholesterol from ABCA1-expressing macrophages to serum from type IV hypertriglyceridemic subjects.
Since elevated plasma triglycerides (TGs) are an independent cardiovascular risk factor, we have compared the cholesterol efflux potential of sera from asymptomatic hypertriglyceridemic (HTG) type IIb, type IV or normolipidemic (NLP) individuals using two different cell systems. In both type IIb and IV HTG, the efflux of cholesterol from SR-BI-rich Fu5AH cells was similar to that obtained with NLP. The maintenance of efflux efficiency in spite of reduced HDL-cholesterol levels can be mainly attributed to the relative enrichment of HDL with phospholipid. In the J774 macrophage cell system, pretreatment with cAMP, which upregulates ABCA1, induced a markedly higher increase in efflux to type IV sera compared with type IIb or NLP. In addition, type IV sera exhibited two-fold higher pre-beta HDL relative concentration (percentage of total apo AI) compared with NLP. Moreover, positive correlations were established between ABCA1-mediated efflux and the serum pre-beta HDL levels or TG concentrations. Thus, the hyperTGemia is associated with a higher fraction of apo AI recovered as pre-beta HDL which appear to be partly responsible for enhanced efflux obtained upon the cAMP stimulation of J774 cells. In conclusion, we demonstrated for the first time that the ABCA1-expressing J774 cell system is responsive to the percent of apo AI present in human serum as pre-beta HDL. Our results suggest that high-plasma TG, accompanied by low HDL may not result in an impaired cholesterol efflux capacity.


Phosphatidylinositol-(3,4,5)-Trisphosphate Induces Phagocytosis of Nonmotile Pseudomonas aeruginosa.
Pathogenic bacteria that establish chronic infections in immunocompromised patients frequently undergo adaptation or selection for traits that are advantageous for their growth and survival. Clinical isolates of Pseudomonas aeruginosa, a Gram-negative, opportunistic bacterial pathogen, exhibit a temporal transition from a motile to a nonmotile phenotype through loss of flagellar motility during the course of chronic infection. This progressive loss of motility is associated with increased resistance to both antibiotic and immune clearance. We have previously shown that loss of bacterial motility enables P. aeruginosa to evade phagocytic clearance both in vitro and in vivo and fails to activate the phosphatidylinositol 3-kinase (PI3K)/Akt-dependent phagocytic pathway. Therefore, we tested the hypothesis that clearance of phagocytosis-resistant bacteria could be induced by exogenously pretreating innate immune cells with the Akt-activating molecule phosphatidylinositol-(3,4,5)-trisphosphate (PIP3). Here, we demonstrate that PIP3 induces the uptake of nonmotile P. aeruginosa by primary human neutrophils >25-fold, and this effect is phenocopied with the use of murine phagocytes. However, surprisingly, mechanistic studies revealed that the induction of phagocytosis by PIP3 occurs because polyphosphoinositides promote bacterial binding by the phagocytes rather than bypassing the requirement for PI3K. Moreover, this induction was selective since the uptake of other nonmotile Gram-negative, but not Gram-positive, bacteria can also be induced by PIP3 Since there is currently no treatment that effectively eradicates chronic P. aeruginosa infections, these findings provide novel insights into a potential methodology by which to induce clearance of nonmotile pathogenic bacteria and into the endogenous determinants of phagocytic recognition of P. aeruginosa.


Influence of photothermal and plasma-mediated nano-processes on fluence thresholds for ultrafast laser-induced cavitation around gold nanoparticles.
Laser fluence thresholds of ultrafast excitation of vapor bubbles around gold nanoparticles are determined experimentally. An optical scattering technique of limited minimum bubble size resolution is employed and analyzed for that purpose. Measurements were performed for spherical gold nanoparticles of varying sizes (40-200 nm) and for laser pulses of varying pulse width (55 fs to 4.3 ps) to estimate the limits where the evaluated thresholds are attributed to either plasma-mediated or photothermal cavitation. Furthermore, thresholds were obtained by double 55 fs pulsed excitation (varying delay 0.0-4.3 ps), providing insights into the dynamics of the excited plasma. A relationship is established between particle properties, (size, near-field amplification factor, and absorption efficiency) and the crossover pulse width of the transition from plasma-mediated to photothermal cavitation. Further, by comparing theory and experiments, we examine the approximative optical breakdown density of ∼10-21 cm-3 at a distance of 1-2 nm from the particle surface as a criterion of plasma-mediated cavitation around gold nanoparticles in analogy to the spinodal criterion for photothermal cavitation. For a given pulse width, the breakdown density appears to be nearly size-independent, establishing the aforesaid criterion applicable. However, a small pulse width dependence of the breakdown density is still observed. Based on these criteria, a comparison is further provided between theoretical thresholds of cavitation and the ones of detectable bubbles. An increasing discrepancy is observed between them with decreasing size for the case of photothermal cavitation. For plasma-mediated cavitation, the latter discrepancy is seemingly smaller, presumably due to the highly nonlinear nature of the process.


Diffuse Idiopathic Skeletal Hyperostosis (DISH)-A Rare Etiology of Dysphagia.
A 72-year-old gentleman presented to the hospital with progressively worsening dysphagia to soft foods and liquids. He was diagnosed with severe pharyngeal dysphagia by modified barium swallow. A CT scan of the neck with IV contrast showed anterior flowing of bridging osteophytes from C3-C6, indicative of DISH, resulting in esophageal impingement. He underwent resection of the DISH segments. Following the surgery, a PEG tube for nutrition supplementation was placed. However, the PEG tube was removed after five months when the speech and swallow evaluation showed no residual dysphagia. DISH is a rare non-inflammatory condition that results in pathological ossification and calcification of the anterolateral spinal ligaments.


Search for Lorentz invariance and CPT violation with the MINOS far detector.
We searched for a sidereal modulation in the MINOS far detector neutrino rate. Such a signal would be a consequence of Lorentz and CPT violation as described by the standard-model extension framework. It also would be the first detection of a perturbative effect to conventional neutrino mass oscillations. We found no evidence for this sidereal signature, and the upper limits placed on the magnitudes of the Lorentz and CPT violating coefficients describing the theory are an improvement by factors of 20-510 over the current best limits found by using the MINOS near detector.


Simple fluorinated moiety insertion on Aβ 16-23 peptide for stain-free TEM imaging.
Peptide aggregation and fibre formation are one of the major underlying causes of several neurodegenerative disorders such as Alzheimer's disease. During the past decades the characterisation of these fibres has been widely studied in an attempt to further understand the nature of the related diseases and in an effort to develop treatments. Transmission electron microscopy (TEM) is one of the most commonly used techniques to identify these fibres, but requires the use of a radioactive staining agent. The procedure we report overcomes this drawback through simple addition of a fluorinated moiety to a short Amyloid β sequence via solid phase peptide synthesis (SPPS). This method is synthetically straightforward, widely applicable to different aggregation-prone sequences and, above all, allows for stain-free TEM imaging with improved quality compared to standard imaging procedures. The presence of the fluorinated moiety does not cause major changes in the fibre structure or aggregation, but rather serves to dissipate the microscope's electron beam, thus allowing for high contrast and straightforward imaging by TEM.


Tooth fragment reattachment through the use of a nanofilled composite resin.
The purpose of this study is to evaluate resistance to fracture with static tests of dental fragments reattached through the use of different light-curing composite resins. For this purpose 40 bovine inferior incisors were utilised, which were randomised into 4 groups; one control group and 3 experimental groups. All teeth of the 3 experimental groups were sawed at 3 mm from the incisal margin, and the respective fragments were then reattached utilizing different composite resins: in group 2_EI the hybrid composite Tetric EvoCeram (Ivoclar Vivadent AG) was used, in group 3_ZI the hybrid composite FiltekTM Z250 (3M ESPE) was used, and in group 4_SN the nanofilled composite FiltekTM Supreme (3M ESPE) was used. After reattachment, on each tooth were performed a chamfer on the buccal surface and an overcontour on the lingual surface along the fracture line, which were then filled with the composite resin corresponding to the respective group. Finally, all teeth were embedded in plaster blocks, and a force was applied on the buccal surface. All teeth in groups 2, 3, and 4 showed a significant loss of resistance to fracture compared to the teeth of the control group (P<0.0001). Resistance to fracture of the teeth belonging to groups 2_EI and 3_ZI was 37.35% and 47.35% of that of intact teeth respectively; in group 4_SN resistance to fracture reached 60.05%. Teeth of group 2 exhibited values of resistance to fracture statistically significant from those of group 4 (P=0.024), but no difference was found between group 2 and group 3 (P=0.298). The difference in resistance between group 3 and group 4 was not statistically significant (P=0.199). Static test showed that reattachment of coronal fragments do not restore resistance to fracture to the value of intact teeth. Resistance to fracture in in vitro studies is influenced by the type of composite resin utilised.


Beyond diphtheria toxin: cytotoxic proteins of Corynebacterium ulcerans and Corynebacterium diphtheriae.
Diphtheria toxin is one of the best investigated bacterial toxins and the major virulence factor of toxigenic Corynebacterium diphtheriae and Corynebacterium ulcerans strains. However, also diphtheria toxin-free strains of these two species can cause severe infections in animals and humans, indicating the presence of additional virulence factors. In this study, we present a first characterization of two proteins with cytotoxic effect in corynebacteria. A putative ribosome-binding protein (AEG80717, CULC809_00177), first annotated in a genome sequencing project of C. ulcerans strain 809, was investigated in detail together with a homologous protein identified in C. diphtheriae strain HC04 (AEX80148, CDHC04_0155) in this study. The corresponding proteins show striking structural similarity to Shiga-like toxins. Interaction of wild-type, mutant and complementation as well as overexpression strains with invertebrate model systems and cell lines were investigated. Depending on the presence of the corresponding genes, detrimental effects were observed in vivo in two invertebrate model systems, Caenorhabditis elegans and Galleria mellonella, and on various animal and human epithelial and macrophage cell lines in vitro. Taken together, our results support the idea that pathogenicity of corynebacteria is a multifactorial process and that new virulence factors may influence the outcome of potentially fatal corynebacterial infections.


Nutrition for the elderly.
Nutrition in the older person is complex because of changing physiology, changes caused by multiple chronic diseases, changes induced by pharmacologic agents, and commonly, failing protein/caloric intake. This article is designed to explain the mechanisms of these processes and to suggest pragmatic and practical responses in the management of the older patient.


Building and using a social network: nurture for low-income Chinese American adolescents' learning.
Little research has examined how low-income Asian American children are supported to achieve well in school. The authors used the notion of social capital to study higher versus lower achieving Chinese adolescents from low-income backgrounds. They found that families of higher-achieving adolescents built and used more effectively three kinds of social networks in lieu of direct parental involvement: (a) designating a helper in and outside the home for the child, (b) identifying peer models for the child to emulate, and (c) involving extended kin to guide the child jointly. These forms of social capital reflect Chinese cultural values applied to the challenges of immigrant adaptation.


Modeling electroencephalography waveforms with semi-supervised deep belief nets: fast classification and anomaly measurement.
Clinical electroencephalography (EEG) records vast amounts of human complex data yet is still reviewed primarily by human readers. Deep belief nets (DBNs) are a relatively new type of multi-layer neural network commonly tested on two-dimensional image data but are rarely applied to times-series data such as EEG. We apply DBNs in a semi-supervised paradigm to model EEG waveforms for classification and anomaly detection. DBN performance was comparable to standard classifiers on our EEG dataset, and classification time was found to be 1.7-103.7 times faster than the other high-performing classifiers. We demonstrate how the unsupervised step of DBN learning produces an autoencoder that can naturally be used in anomaly measurement. We compare the use of raw, unprocessed data--a rarity in automated physiological waveform analysis--with hand-chosen features and find that raw data produce comparable classification and better anomaly measurement performance. These results indicate that DBNs and raw data inputs may be more effective for online automated EEG waveform recognition than other common techniques.


Gender, menstrual cycle, oral contraceptives and red blood cell deformability in healthy adult subjects.
Gender, menstrual cycle and oral contraceptives may have influence on mechanical properties of Red Blood Cell (RBC) and particularly on RBC deformability. So cell transit parameters have been assessed by filtration with the Cell Transit Analyser (CTA) for a large healthy adult population (seventy-nine males and one-hundred-fifteen females). The CTA provides the distribution of cell transit times of 5000 red blood cells, the mean transit time of the population and different percentiles such as p50, p75, p90 and p95. No effect of oral contraceptives was found. Nevertheless, influence of sex and menstrual cycle were demonstrated. A significant increase of the filtration parameters measured in the female population with respect to the male population and during menstruation, preovulation and post-ovulation periods was observed. During ovulation, the CTA parameters are comparable to the same parameters found in males.


Stroke without dissection from a neck holding manoeuvre in martial arts.
Carotid artery trauma is a known cause of stroke in young people. The vessel may occlude, dissect or shower thrombotic emboli into intracranial vessels. This paper reports the use of single photon emission computed tomography (SPECT) imaging in a 29 year old man who developed an embolic stroke after neck holding manoeuvres at a martial arts class. Awareness of the potential consequences of these procedures is matched by the need for rapid and accurate diagnosis of stroke now that thrombolytic and neuroprotective treatments are emerging, which are effective only within a short time window.


Antibiotic resistance in children with recurrent or complicated urinary tract infection.
Urinary tract infection is certainly one of the most common childhood infections. Emerging resistance to the antibiotics is not unusual. Current hospitalization for children with urinary tract infection is reserved for severe or complicated cases. The aim of the present study was to determine the antibiotic resistance pattern among children with recurrent or complicated urinary tract infection. A retrospective study carried out at Prince Hashem hospital, Zarqa city, eastern Jordan and involved 336 episodes of culture proved urinary tract infection obtained from 121 patients with recurrent UTI, who used prophylactic antibiotics during the period from April 1, 2004 to December 31, 2006. The isolated microorganisms and there antibiotics susceptibility were studied. Seventy three patients (60.3%) were found to have some forms of urinary tract anomaly, significantly more prevalent among male children P<0.001. Vesicoureteral reflux being the most common (58.9%). Renal scars were significantly more prevalent among those with complicated rather than recurrent urinary tract infection (64.3% vs. 16.6%, P<0.001). Gram negative organisms were the most frequent isolates in patients with recurrent and complicated urinary tract infection. Proteus, Pseudomonas and Candida spp. were more prevalent in patients with complicated (P<0.001), and isolates in patients with UTA were significantly more resistant to most antibiotics tested. Pediatric urine culture isolates are becoming increasingly resistant to commonly used antibiotics. Empirical treatment with Trimethoprim-Sulfamethoxazole (TMP-SMX) or Cephalexin as the initial drug is ineffective. Nitrofurantoin and Nalidixic acid can be considered as the first line antibiotics for prophylaxis and or treatment of patients with recurrent UTI, while Meropenam and Ciprofloxacin can be used empirically in treating patients with complicated UTI.


Interaction between betamethasone and vecuronium.
A possible interaction between betamethasone and vecuronium was examined in 20 rat phrenic nerve-hemidiaphragm preparations. Ten preparations were bathed in a physiological solution with betamethasone 1 mumol litre-1 added and, after a 30-min period were exposed to vecuronium at concentrations of 4, 6, 8 and 10 mumol litre-1 with vecuronium free washings between each exposure. Ten control experiments were performed also using a betamethasone-free bathing solution. In comparison with control, the betamethasone group had significantly (P = 0.0008) less depression of muscle contraction (twitch) force at all concentrations of vecuronium. The calculated ED50 (50% depression of muscle contraction force) was 5.65 mumol litre-1 for controls and 7.39 mumol litre-1 for betamethasone-pretreated preparations. This study confirms our previous clinical observations that an interaction occurs between vecuronium and betamethasone which is characterized by resistance to neuromuscular block.


Intra-alveolar tissue factor pathway inhibitor is not sufficient to block tissue factor procoagulant activity.
The alveolar compartment in acute lung injury contains high levels of tissue factor (TF) procoagulant activity favoring fibrin deposition. We previously reported that the alveolar epithelium can release TF procoagulant activity in response to a proinflammatory stimulus. To test the hypothesis that the alveolar epithelium further modulates intra-alveolar fibrin deposition through secretion of an endogenous inhibitor to TF, tissue factor pathway inhibitor (TFPI), we measured TFPI levels in edema fluid (EF) from patients with acute respiratory distress syndrome. To determine whether the alveolar epithelium can release TFPI, both full-length TFPI and truncated TFPI were measured (ELISA) in pulmonary edema fluid from patients with acute respiratory distress syndrome (ARDS) and a control group of patients with hydrostatic pulmonary edema (HYDRO). TFPI protein was also measured in conditioned media (CM) and cell lysates (CL) from human alveolar epithelial cells (A549) after exposure to cytomix (TNF-alpha, IL-1 beta, IFN-gamma). TFPI protein levels were higher in pulmonary edema fluid from patients with ARDS vs. HYDRO. TFPI protein was increased in CM and did not change in CL after cytomix treatment; TFPI mRNA levels (RT-PCR) did not change. Despite the high levels of TFPI, both the EF and CM retained significant TF procoagulant activity as measured by plasma recalcification time. The majority of intra-alveolar TFPI was in a truncated, inactive form, whereas the majority of TFPI released from cells was full length, suggesting different mechanisms of inactivation. In summary, the alveolar epithelium releases TFPI in response to an inflammatory stimulus but does not increase TFPI gene transcription or protein production. Levels of intra-alveolar TFPI in ARDS are not sufficient to block intra-alveolar TF procoagulant activity due to truncation and inactivation of intra-alveolar TFPI.


Caring for elder parents: a comparative evaluation of family leave laws.
As the baby boomer generation ages, the need for laws to enhance quality of life for the elderly and meet the increasing demand for family caregivers will continue to grow. This paper reviews the national family leave laws of nine major OECD countries (Canada, Denmark, France, Germany, Italy, Japan, Netherlands, Spain, and the United Kingdom) and provides a state-by-state analysis within the U.S. We find that the U.S. has the least generous family leave laws among the nine OECD countries. With the exception of two states (California and New Jersey), the U.S. federal Family Medical Leave Act of 1993 provides no right to paid family leave for eldercare. We survey the current evidence from the literature on how paid leave can impact family caregivers' employment and health outcomes, gender equality, and economic arguments for and against such laws. We argue that a generous and flexible family leave law, financed through social insurance, would not only be equitable, but also financially sustainable.


Borderline personality: traits and disorder.
Although the 5-factor model (FFM) has been advocated as an alternative to representing the construct of borderline personality, some argue that this diagnosis carries essential information that is not well captured by the FFM. The present study examined antecedent, concurrent, and predictive markers of construct validity in a sample of 362 patients with personality disorders. The results indicated that neuroticism best distinguished borderline and nonborderline patients, whereas the FFM as a whole captured a sizable proportion of the variance in the borderline diagnosis. However, the residual of the borderline diagnosis that was not explained by the FFM was found to be significantly related to childhood abuse history, family history of mood and substance use disorders, concurrent symptoms, and 2-year and 4-year outcomes. Thus, some elements of the borderline diagnosis may not be fully captured in a 5-factor representation.


Pathomechanism Characterization and Potential Therapeutics Identification for Parkinson's Disease Targeting Neuroinflammation.
Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the loss of dopaminergic (DAergic) neurons and the presence of α-synuclein-containing Lewy bodies. The unstructured α-synuclein forms insoluble fibrils and aggregates that result in increased reactive oxygen species (ROS) and cellular toxicity in PD. Neuroinflammation engaged by microglia actively contributes to the pathogenesis of PD. In this study, we showed that VB-037 (a quinoline compound), glycyrrhetic acid (a pentacyclic triterpenoid), Glycyrrhiza inflata (G. inflata, a Chinese herbal medicine), and Shaoyao Gancao Tang (SG-Tang, a formulated Chinese medicine) suppressed the nitric oxide (NO) production and interleukin (IL)-1β maturation in α-synuclein-stimulated BV-2 cells. Mouse inflammation antibody array further revealed increased IL-1α, IL-1β, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) expression in α-synuclein-inflamed BV-2 cells and compound pretreatment effectively reduced the expression and release of these pro-inflammatory mediators. The test compounds and herbal medicines further reduced α-synuclein aggregation and associated oxidative stress, and protected cells against α-synuclein-induced neurotoxicity by downregulating NLR family pyrin domain containing 1 (NLRP1) and 3 (NLRP3), caspase 1, IL-1β, IL-6, and associated nuclear factor (NF)-κB inhibitor alpha (IκBα)/NF-κB P65 subunit (P65), c-Jun N-terminal kinase (JNK)/proto-oncogene c-Jun (JUN), mitogen-activated protein kinase 14 (P38)/signal transducer and activator of transcription 1 (STAT1) and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathways in dopaminergic neurons derived from α-synuclein-expressing SH-SY5Y cells. Our findings indicate the potential of VB-037, glycyrrhetic acid, G. inflata, and SG-Tang through mitigating α-synuclein-stimulated neuroinflammation in PD, as new drug candidates for PD treatment.


Gut Microbiome Composition in Obese and Non-Obese Persons: A Systematic Review and Meta-Analysis.
Whether the gut microbiome in obesity is characterized by lower diversity and altered composition at the phylum or genus level may be more accurately investigated using high-throughput sequencing technologies. We conducted a systematic review in PubMed and Embase including 32 cross-sectional studies assessing the gut microbiome composition by high-throughput sequencing in obese and non-obese adults. A significantly lower alpha diversity (Shannon index) in obese versus non-obese adults was observed in nine out of 22 studies, and meta-analysis of seven studies revealed a non-significant mean difference (-0.06, 95% CI -0.24, 0.12, I2 = 81%). At the phylum level, significantly more Firmicutes and fewer Bacteroidetes in obese versus non-obese adults were observed in six out of seventeen, and in four out of eighteen studies, respectively. Meta-analyses of six studies revealed significantly higher Firmicutes (5.50, 95% 0.27, 10.73, I2 = 81%) and non-significantly lower Bacteroidetes (-4.79, 95% CI -10.77, 1.20, I2 = 86%). At the genus level, lower relative proportions of Bifidobacterium and Eggerthella and higher Acidaminococcus, Anaerococcus, Catenibacterium, Dialister, Dorea, Escherichia-Shigella, Eubacterium, Fusobacterium, Megasphera, Prevotella, Roseburia, Streptococcus, and Sutterella were found in obese versus non-obese adults. Although a proportion of studies found lower diversity and differences in gut microbiome composition in obese versus non-obese adults, the observed heterogeneity across studies precludes clear answers.


Brain tryptophan hydroxylation: dependence on arterial oxygen tension.
The accumulation of cerebral 5-hydroxytryptophan after decarboxylase inhibition was decreased in rats maintained at arterial O(2) tensions below 60 mm-Hg. In contrast, brain lactate was stable above 40 mm-Hg and brain adenosine triphosphate, adenosine diphosphate, and adenosine monophosphate were unchanged above 30 mm-Hg. There was a linear correlation of brain 5-hydroxytryptophan accumulation to cerebral venous O(2) tension. Cerebral tryptophan hydroxylase appears to have a poor affinity for oxygen and to be affected by slight hypoxia. The resultant decreases in monoamine neurotransmitter metabolism may explain the behavioral changes of mild oxygen deprivation.


T lymphocyte colony formation and autoimmune disease: in vitro assessment of immunopathology.
Human T lymphocyte colonies were generated with phytohemagglutinin in semi-solid media to assess the influence of cellular and humoral components upon colony formation by patients with systemic lupus erythematosus (SLE) compared to normal age-matched controls. Optimal colony formation occurred for patients with SLE and controls approximately 6 d after culture. However, colony formation by patients with active disease was significantly reduced compared to both controls and patients with inactive disease. Similar results were obtained in liquid cultures. There was no statistical correlation between colony forming capacity and quantitation of liquid culture transformation. Observation of the influences of patient sera produced striking dose response relationships. SLE sera were found to inhibit colony formation at high concentration (30-190%) but enhanced at lower concentrations (25-694%).


Analgesia after thoracotomy in children: a comparison of interpleural, epidural, and intravenous analgesia.
The cohort for this study included 39 patients, between the ages of 8 and 20 years, who had had thoracotomy. Postoperative analgesia was provided by one of three techniques: intravenous narcotics (20 patients), thoracic epidural catheter (10 patients), or interpleural analgesia (IPA) (nine patients). Both IPA and epidural analgesia were administered according to a specific protocol. The efficacy of the three methods was evaluated using two indicators: the total intravenous narcotic requirements for the initial 72 hours and the number of times a dose of intravenous narcotic or supplemental epidural fentanyl was administered to each patient. Patients in the IPA group required significantly less intravenous narcotics (P less than .05) during the first three postoperative days (2.2 +/- 0.4, 1.9 +/- 0.6, and 1.4 +/- 0.5 mg of meperidine/kg/day) than patients in the intravenous narcotic group (8.1 +/- 1.2, 7.2 +/- 0.9, and 5.6 +/- 1.2 mg of meperidine/kg/day). When comparing epidural analgesia and IPA, the number of interventions in the patients receiving epidural analgesia was significantly less (P less than .05) than in the group receiving IPA. Four of 10 patients in the epidural group and two of nine in the IPA group required no interventions during the initial 72-hour postoperative course. In the epidural analgesia group, there were 19 days (of a total of 30 days) during which patients required no interventions. This percentage was significantly greater (P less than .05) than that of the IPA group, in which there were 9 days (of a total of 27 days), during which no interventions were required.


Effects of an intrahypothalamic injection of antisense oligonucleotides for preproenkephalin mRNA in female rats: evidence for opioid involvement in lordosis reflex.
Previous studies in female rats have shown that estrogen increases preproenkephalin (PPE) mRNA levels in the ventrolateral part of the ventromedial nucleus of the hypothalamus (VMHVL), an area implicated in the modulation of sexual behavior. In order to assess the physiological role of hypothalamic opioid expression in lordosis reflex 16-mer oligodeoxynucleotide (ODN) directed towards the PPE mRNA were acutely microinjected above the VMH of estradiol-primed ovariectomized rats. Estradiol-induced lordosis behavior was observed in response to a stud male 2 days thereafter. Antisense (without or with 4 mismatches) ODN injections near the VMHVL resulted in a significant reduction in lordosis quotient compared to control (reverse sense) ODN treatment or to antisense ODN injections targeted anterior or posterior to the VMHVL. In contrast, locomotor activity of these animals in the open-field test was not affected by ODN treatments. Enkephalin immunoreactive levels were determined by radioimmunoassay in the preoptic area, a major terminal field of the VMHVL. Estradiol-induced enkephalin levels were greatly reduced in antisense-treated groups. Using the in situ hybridization technique, PPE mRNA levels in the VMHVL were also determined. A 1.5-2-fold increase in PPE mRNA levels was observed in estradiol-treated rats compared to ovariectomized rats as previously described. This increase in PPE mRNA levels was not affected by ODN treatment, suggesting that the reduction of enkephalin expression was mainly due to physical blockade of PPE mRNA translation and not to its degradation. Taken together, these data further support the behavioral role of PPE expressing VMHVL neurons. They also highlight the in vivo potency of acute administration of antisense phosphorothioate ODNs in blocking neuronal target gene expression.


Comparative study on menstrual disorders in post-tubal ligated and non-ligated women.
The term post-tubal sterilization syndrome has been used variously to include abnormal menstrual bleeding, pre-menstrual dysmenorrhea distress, hysterectomy, and miscellaneous other conditions like the need for recanalization, the feeling of regret, and menopausal syndrome. To compare the menstrual disorders in post-tubal ligated and non-ligated women and also to compare the histopathology of endometrium in both post-tubal ligated and non-ligated groups in order to compare the menstrual disorders. It is a comparative cross-sectional study on 200 women between 30 and 50 years, divided into two groups and further into two sub-groups in each group. Group 1 includes cases (post-tubal ligated), and group 2 includes controls (non-tubal ligated); sub-group I includes patients with abnormal uterine bleeding (AUB), and sub-group II includes patients without AUB. Data were recorded using standard performa along with investigations and detailed examination. In the case group (post-tubal ligated), maximum patients of 39.22% were having polymenorrhea and 29.41% patients had menorrhagia, whereas in the control group (non-tubal ligated), maximum patients of 38.78% had polymenorrhea and 30.61% had menorrhagia, respectively. However, the difference is statistically non-significant (P value = 1.00). Our study suggests that the incidence of menstrual disorders did not differ significantly with tubal ligation. The patients worried about the effects of tubal ligation on their future life that must be counseled and that tubal ligation has no adverse effect on their life including their menstrual pattern. The findings of the study help family physicians in educating the clientele. We also recommend large studies with multiple centers so as to give statistically significant findings of associations.