Hypertension in chronic kidney disease: navigating the evidence.
Hypertension is both an important cause and consequence of chronic kidney disease. Evidence from numerous clinical trials has demonstrated the benefit of blood pressure control. However, it remains unclear whether available results could be extrapolated to patients with chronic kidney diseases because most studies on hypertension have excluded patients with kidney failure. In addition, chronic kidney disease encompasses a large group of clinical disorders with heterogeneous natural history and pathogenesis. In this paper, we review current evidence supporting treatment of hypertension in various forms of chronic kidney disease and highlight some of the gaps in the extant literature.


On the morphology of the brachial plexus of the platypus (Ornithorhynchus anatinus) and the echidna (Tachyglossus aculeatus).
Four forelimbs of 3 platypuses and 3 forelimbs of 2 echidnas were examined to study the precise form of the brachial plexus and to clarify the structural characteristics of the brachial plexus in phylogeny. The spinal components contributing to the plexus (C4-T2) and the formation patterns of the 3 trunks of the plexus were the same as those generally observed in mammals. In the cranial half of the brachial plexus from C4, 5 and 6 in monotremes, division into the ventral bundle (lateral cord) and dorsal bundle (axillary nerve) is clear, as in other mammals. However, for monotremes, in the caudal half of the plexus from C7 and T1 (+T2) and the nerves arising from the caudal plexus there is no definite division into the ventral and dorsal bundles, which distribute to the flexor and extensor parts of the forelimbs, respectively. The lower trunk of the monotreme brachial plexus forms a cord which contains both ventral and dorsal components. This characteristic diverges from the generally accepted idea that the tetrapod limb plexus is divided clearly into 2 layers: a dorsal layer for extensors and a ventral layer for flexors of the limb. Considering the incomplete dorsoventral division of forelimb nerves in some reptiles and urodeles, the caudal half of the monotreme brachial plexus has characteristics in common with those of lower tetrapods.


Template switching by reverse transcriptase during DNA synthesis.
The ability of reverse transcriptase to make template switches during DNA synthesis is implicit in models of retrovirus genome replication, as well as in recombination and oncogene transduction. In order to understand such switching, we used in vitro reactions with purified nucleic acids and enzymes. The assay system involved the use of an end-labeled DNA primer so as to allow the quantitation of elongation on a donor template relative to the amount of elongation achieved by template switching (by means of sequence homology) when an acceptor template RNA was added. We examined several variables that affected the efficiency of the reaction: (i) the reaction time, (ii) the relative amounts of acceptor and donor template, (iii) the extent of sequence overlap between the donor and acceptor templates, and (iv) the presence or absence of RNase H activity associated with the reverse transcriptase. The basic reaction, with RNA templates and normal reverse transcriptase, yielded as much as 83% template switching. In the absence of RNase H, switching still occurred but the efficiency was lowered. Also, when the donor template was changed from RNA to DNA, there was still switching; not surprisingly, this was largely unaffected by the presence or absence of RNase H. Finally, we examined the action of the RNase H on RNA templates after primary transcription but prior to template switching. We found that in most cases, both ends of the original RNA template were able to maintain an association with the DNA product. This result was consistent with the work of others who have shown that RNase H acts as an endonuclease.


Alteration in endometrial proteins during early- and mid-secretory phases of the cycle in women with unexplained infertility.
Compromised receptivity of the endometrium is a major cause of unexplained infertility, implantation failure and subclinical pregnancy loss. In order to investigate the changes in endometrial protein profile as a cause of unexplained infertility, the current study was undertaken to analyze the differentially expressed proteins of endometrium from early-secretory (LH+2) to mid-secretory phase (LH+7), in women with unexplained infertility. 2-D gel electrophoresis was performed to analyze the proteomic changes between early- (n = 8) and mid-secretory (n = 8) phase endometrium of women with unexplained infertility. The differentially expressed protein spots were identified by LC-MS analysis and validated by immunoblotting and immuno-histochemical analysis in early- (n = 4) and mid-secretory (n = 4) phase endometrium of infertile women. Validated proteins were also analyzed in early- (n = 4) and mid-secretory (n = 4) phase endometrium of fertile women. Nine proteins were found to be differentially expressed between early- and mid- secretory phases of endometrium of infertile women. The expression of Ras-related protein Rap-1b, Protein disulfide isomerase A3, Apolipoprotein-A1 (Apo-A1), Cofilin-1 and RAN GTP-binding nuclear protein (Ran) were found to be significantly increased, whereas, Tubulin polymerization promoting protein family member 3, Superoxide dismutase [Cu-Zn], Sorcin, and Proteasome subunit alpha type-5 were significantly decreased in mid- secretory phase endometrium of infertile women as compared to early-secretory phase endometrium of infertile women. Validation of 4 proteins viz. Sorcin, Cofilin-1, Apo-A1 and Ran were performed in separate endometrial biopsy samples from infertile women. The up-regulated expression of Sorcin and down-regulated expression of Cofilin-1 and Apolipoprotein-A1, were observed in mid-secretory phase as compared to early-secretory phase in case of fertile women. De-regulation of the expression of Sorcin, Cofilin-1, Apo-A1 and Ran, during early- to mid-secretory phase may have physiological significance and it may be one of the causes for altered differentiation and/or maturation of endometrium, in women with unexplained infertility.


CXCR2 antagonist attenuates neutrophil transmigration into brain in a murine model of LPS induced neuroinflammation.
Sepsis-associated encephalopathy (SAE) is a devastating neurological complication of sepsis with intolerable high motility. SAE is accompanied with brain vascular injury, endothelial hyperpermeability, and neutrophil infiltration into the brain tissue, key inflammatory processes leading to further brain edema and neuronal cell apoptosis. Recent studies from us and others suggest that the chemokine receptor C-X-C Motif Chemokine Receptor 2 (CXCR2) is crucial for neutrophil recruitment during SAE. Here we use CXCR2 antagonist SB225002 to characterize the role of CXCR2 in brain infiltration of neutrophil in a murine model of SAE. Systemic administration of high-dose LPS (10 mg/kg) induced evident neutrophil infiltration into the cerebral cortex in wild-type mice. However, CXCR2 antagonist SB225002 markedly attenuated neutrophil infiltration into brain. The CXCR2 expression on neutrophils in the peripheral circulation was dramatically downregulated in response to this LPS dose, and endothelial CXCR2 was significantly upregulated, suggesting endothelial but not neutrophil CXCR2 plays a more important role in neutrophil infiltration into brain. Strikingly, although these CXCR2 antagonist SB225002 treated mice displayed reduced neutrophil infiltration, no change in neutrophil rolling and adhesion was observed. Furthermore, we confirmed that CXCR2 agonist CXCL1 induced a marked increase in actin stress fiber synthesis and paracellular gap formation in cultured cerebral endothelial cells, which is attenuated by SB225002. Thus, these results demonstrate a selective role for endothelial CXCR2 to regulate cerebral vascular permeability and neutrophil transmigration in high-dose LPS induced neuroinflammation, and also suggest a therapeutic potential of CXCR2 antagonist SB225002 in SAE.


Affinity capillary electrophoresis: a physical-organic tool for studying interactions in biomolecular recognition.
Affinity capillary electrophoresis (ACE) is a technique that is used to measure the binding affinity of receptors to neutral and charged ligands. ACE experiments are based on differences in the values of electrophoretic mobility of free and bound receptor. Scatchard analysis of the fraction of bound receptor, at equilibrium, as a function of the concentration of free ligand yields the dissociation constant of the receptor-ligand complex. ACE experiments are most conveniently performed on fused silica capillaries using a negatively charged receptor (molecular mass < 50 kDa) and increasing concentrations of a low molecular weight, charged ligand in the running buffer. ACE experiments that involve high molecular weight receptors may require the use of running buffers containing zwitterionic additives to prevent the receptors from adsorbing appreciably to the wall of the capillary. This review emphasizes ACE experiments performed with two model systems: bovine carbonic anhydrase II (BCA II) with arylsulfonamide ligands and vancomycin (Van), a glycopeptide antibiotic, with D-Ala-D-Ala (DADA)-based peptidyl ligands. Dissociation constants determined from ACE experiments performed with charged receptors and ligands can often be rationalized using electrostatic arguments. The combination of differently charged derivatives of proteins - protein charge ladders - and ACE is a physical-organic tool that is used to investigate electrostatic effects. Variations of ACE experiments have been used to estimate the charge of Van and of proteins in solution, and to determine the effect of the association of Van to Ac2KDADA on the value of pKa of its N-terminal amino group.


Using pulsatile pressure saline/antibiotic irrigation before reduction and fixation of infected mandibular fractures: literature review and report of two cases.
The efficacy of pulsatile pressure saline irrigation has been demonstrated in the orthopedic, surgical, and dental literature. However, its use for treating infected mandibular fractures has not been documented. This article reviews the literature concerning pressure irrigation. The pulsatile pressure saline/antibiotic irrigation technique and indications for its use during the treatment of infected mandibular fractures are demonstrated with two case reports. The pulsatile pressure saline/antibiotic irrigation system is a useful adjunct to the standard therapeutic modalities of infection management. It is also useful for managing infected mandibular fractures, especially when open reduction and internal fixation with bone plates have been planned.


Depression Level and Its Associated Factors among Postpartum Working Women in Kuching, Sarawak-A Cross-Sectional Study.
Postpartum depression (PD) among women, if left untreated, may result in long-term health and social consequences for them and their families. This cross-sectional study aimed to determine the factors contributing to PD among working mothers in Kuching, Sarawak, Malaysia. Systematic sampling was used to recruit working mothers who attended Kuching's maternal and child health clinics. They were interviewed with a validated translated questionnaire to obtain data on sociodemographics, health profiles, and Edinburgh Postnatal Depression Scale (EPDS) and postpartum symptoms. Data were analysed using IBM SPSS version 21.0. Out of the total 281 respondents, 15.3% of respondents had depression symptoms. Fatigue (42.7%), back or neck pain (36.3%), breast discomfort (16.4%), dizziness (13.5%) and nipple irritation (11.0%) were the most common physical symptoms experienced by the mothers. Regression analysis showed that working mothers who exhibited higher scores of physical symptoms were 1.26 times more likely to develop PD (adjusted odd ratio 1.26, P < 0.01; 95% CI: 1.071, 1.487). Physical symptoms were the predictors of PD among working mothers.


Variations of supraorbital traits.
More than one notch and/or foramen may be found in the supraorbital region due to branching of the supraorbital nerves and vessels. A total of 360 adult Anatolian-Ottoman skulls (212 male, 148 female) were examined for some characteristics of the notches and/or foramina in the supraorbital region. The distribution of the supraorbital traits: 335 (93%) in medial, 24 (6.7%) in both medial and lateral, only 1 (0.3%) in lateral position. Of 360 skulls, 197 (54.7%) had one notch on either side, 32 (8.9%) had one foramen on one side and one notch on the other side, 24 (6.7%) had one foramen and notch on one side and one notch on the other side, 19 (5.3%) had one foramen on either side and 88 (24.4%) had other combinations. The distances of the notches from the midline, and between of the foramina from the midline and the supraorbital margin were measured. Knowledge of the anatomy of the supraorbital region is important for the plastic and maxillofacial surgery.


Pyrrolylquinoxaline-2-One Derivative as a Potent Therapeutic Factor for Brain Trauma Rehabilitation.
Traumatic brain injury (TBI) often causes massive brain cell death accompanied by the accumulation of toxic factors in interstitial and cerebrospinal fluids. The persistence of the damaged brain area is not transient and may occur within days and weeks. Chaperone Hsp70 is known for its cytoprotective and antiapoptotic activity, and thus, a therapeutic approach based on chemically induced Hsp70 expression may become a promising approach to lower post-traumatic complications. To simulate the processes of secondary damage, we used an animal model of TBI and a cell model based on the cultivation of target cells in the presence of cerebrospinal fluid (CSF) from injured rats. Here we present a novel low molecular weight substance, PQ-29, which induces the synthesis of Hsp70 and empowers the resistance of rat C6 glioma cells to the cytotoxic effect of rat cerebrospinal fluid taken from rats subjected to TBI. In an animal model of TBI, PQ-29 elevated the Hsp70 level in brain cells and significantly slowed the process of the apoptosis in acceptor cells in response to cerebrospinal fluid action. The compound was also shown to rescue the motor function of traumatized rats, thus proving its potential application in rehabilitation therapy after TBI.


Modularized CRISPR/dCas9 effector toolkit for target-specific gene regulation.
The ability to control mammalian genes in a synergistic mode using synthetic transcription factors is highly desirable in fields of tissue engineering, stem cell reprogramming and fundamental research. In this study, we developed a standardized toolkit utilizing an engineered CRISPR/Cas9 system that enables customizable gene regulation in mammalian cells. The RNA-guided dCas9 protein was implemented as a programmable transcriptional activator or repressor device, including targeting of endogenous loci. For facile assembly of single or multiple CRISPR RNAs, our toolkit comprises a modular RNAimer plasmid, which encodes the required noncoding RNA components.


Immunosuppressive effects of multipotent mesenchymal stromal cells on graft-versus-host disease in rats following allogeneic bone marrow transplantation.
Graft-versus-host disease (GVHD) is a major obstacle to successful allogeneic bone marrow transplantation (allo-BMT). While multipotent mesenchymal stromal cells (MSCs) demonstrate alloresponse in vitro and in vivo, they also have clinical applications toward prevention or treatment of GVHD. The aim of this study was to investigate the ability of MSCs to prevent or treat GVHD in a rat BMT model. The GVHD model was established by transplantation of Sprague Dawley rats' bone marrow and spleen cells into lethally irradiated (950 cGy) SDxWistar rat recipients. A total of 49 rats were randomly assigned to 4 study and 3 control groups administered different GVHD prophylactic regimens including MSCs. After transplantation, clinical GVHD scores and survival status were monitored. All irradiated and untreated control mice with GVHD died. MSCs inhibited lethal GVHD as efficiently as the standard GVHD prophylactic regimen. The gross and histopathological findings of GVHD and the ratio of CD4/CD8 expression decreased. The subgroup given MSCs displayed higher in vivo proportions of CD25+ T cells and plasma interleukin-2 levels as compared to conventional GVHD treatment after allo-BMT. Our results suggest that clinical use of MSCs in both prophylaxis against and treatment of established GVHD is effective. This study supports the use of MSCs in the prophylaxis and treatment of GVHD after allo-BMT; however, large scale studies are needed. None declared.


Optimizing searches via rare events.
Randomized search algorithms for hard combinatorial problems exhibit a large variability of performances. We study the different types of rare events which occur in such out-of-equilibrium stochastic processes and we show how they cooperate in determining the final distribution of running times. As a by-product of our analysis we show how search algorithms are optimized by random restarts.


Basic mechanisms of epileptogenesis in pediatric cortical dysplasia.
Cortical dysplasia (CD) is a neurodevelopmental disorder due to aberrant cell proliferation and differentiation. Advances in neuroimaging have proven effective in early identification of the more severe lesions and timely surgical removal to treat epilepsy. However, the exact mechanisms of epileptogenesis are not well understood. This review examines possible mechanisms based on anatomical and electrophysiological studies. CD can be classified as CD type I consisting of architectural abnormalities, CD type II with the presence of dysmorphic cytomegalic neurons and balloon cells, and CD type III which occurs in association with other pathologies. Use of freshly resected brain tissue has allowed a better understanding of basic mechanisms of epileptogenesis and has delineated the role of abnormal cells and synaptic activity. In CD type II, it was demonstrated that balloon cells do not initiate epileptic activity, whereas dysmorphic cytomegalic and immature neurons play an important role in generation and propagation of epileptic discharges. An unexpected finding in pediatric CD was that GABA synaptic activity is not reduced, and in fact, it may facilitate the occurrence of epileptic activity. This could be because neuronal circuits display morphological and functional signs of dysmaturity. In consequence, drugs that increase GABA function may prove ineffective in pediatric CD. In contrast, drugs that counteract depolarizing actions of GABA or drugs that inhibit the mammalian target of rapamycin (mTOR) pathway could be more effective.


Data harmonization process for creating the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention Atlas.
In 2009, the CDC National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP) initiated the online, interactive NCHHSTP Atlas. The goal of the Atlas is to strengthen the capacity to monitor the diseases overseen by NCHHSTP and to illustrate demographic, spatial, and temporal variation in disease patterns. The Atlas includes HIV, AIDS, viral hepatitis, sexually transmitted disease, and tuberculosis surveillance data, and aims to provide a single point of access to meet the analytical and data dissemination needs of NCHHSTP. To accomplish this goal, an NCHHSTP-wide Data Harmonization Workgroup reviewed surveillance data collected by each division to harmonize the data across diseases, allowing one to query data and generate comparable maps and tables via the same user interface. Although we were not able to harmonize all data elements, data standardization is necessary and work continues toward that goal.


Importance sampling as an efficient strategy for the conformational analysis of flexible molecules.
We propose an importance sampling technique for the conformational analysis of flexible molecules that bridges the gap between currently used uniform random search and random walk methods, and compare performances of these methods in their application to selected open-chain and closed-ring hydrocarbons. It is suggested that, if no information on conformational properties of a molecule is available, the optimum strategy of its conformational analysis should include a uniform random search followed by an importance sampling biased as prescribed by the uniform search and concluded by a random-walk or genetic algorithm routine to rectify the properties of the most important parts of the conformational space.


RS3PE Syndrome with Subsequent PMR Caused by Long-Term DPP-4 Inhibitor Use.
Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome has been reported in patients treated with dipeptidyl peptidase-4 inhibitors (DPP-4i). We experienced a case of RS3PE syndrome in a 73-year-old man with a history of type 2 diabetes, who developed RS3PE as a side effect of vildagliptin. Further to this, the patient developed polymyalgia rheumatica (PMR), the first such case associated with long-term DPP-4i use. RS3PE syndrome and PMR are rare diseases that cause painful extremities in adults. We need to know if it occurs by DPP-4i.RS3PE syndrome and PMR can be complicated with malignancy or giant cell arteritis. However, we must rule out side effects of drugs at first from the standpoint of medical resources.


Microglia-derived TGF-β1 ligand maintains microglia homeostasis via autocrine mechanism and is critical for normal cognitive function in adult mouse brain.
While TGF-β signaling is essential for microglial function, the cellular source of TGF-β ligand and its spatial regulation remains unclear in the adult CNS. Our data support that microglia, not astrocytes or neurons, are the primary producers of TGF-β1 ligands needed for microglial homeostasis. Microglia (MG)-Tgfb1 inducible knockout (iKO) leads to the activation of microglia featuring a dyshomeostatic transcriptomic profile that resembles disease-associated microglia (DAMs), injury-associated microglia, and aged microglia, suggesting that microglial self-produced TGF-β1 ligands are important in the adult CNS. Interestingly, astrocytes in MG-Tgfb1 iKO mice show a transcriptome profile that closely aligns with A1-like astrocytes. Additionally, using sparse mosaic single-cell microglia iKO of TGF-β1 ligand, we established an autocrine mechanism for TGF-β signaling. Importantly MG-Tgfb1 iKO mice show cognitive deficits, supporting that precise spatial regulation of TGF-β1 ligand derived from microglia is critical for the maintenance of brain homeostasis and normal cognitive function in the adult brain.


Tocilizumab therapy for persistent high-grade fever in systemic lupus erythematosus: two cases and a literature review.
Tocilizumab (TCZ) is a humanized immunoglobulin (Ig) G1 monoclonal antibody directed against the interleukin (IL)-6 receptor. We report on two patients with persistent high-grade fever and systemic lupus erythematosus (SLE) who were treated with TCZ. Two female Chinese patients presented with SLE and high-grade fever, with raised inflammatory markers including C-reactive protein, erythrocyte sedimentation rate, and IL-6, but no signs of opportunistic infections. Their fever and other symptoms responded poorly to broad-spectrum antibiotics, antifungals, antivirals, and glucocorticoids. They were both treated with TCZ. Their body temperatures returned to normal after treatment with TCZ, and other symptoms, including arthralgia, gradually improved. Both patients were followed-up and their conditions remained steady to date. TCZ may thus be an alternative treatment for patients with SLE and persistent high-grade fever who fail to respond to initial antibiotics and high-dose glucocorticoids.


Achieving comprehensive critical care.
The policy document, Comprehensive Critical Care, suggested that patients with critical care needs should expect the same standard of care wherever they are nursed, be that in a traditional critical care setting or in a general ward area. It is recognized that in order for this to occur, the developmental needs of ward nurses need to be met to enable them to care for patients with level 1 and level 2 needs. A second document, The Nursing Contribution to the Provision of Comprehensive Critical Care for Adults: A strategic Programme of Action, proposed a programme of action and outlined five priority areas to be considered to ensure the success of comprehensive critical care. Education, training and workforce development was one of the areas outlined, and thus, in response, the role of the practice development facilitator was created as a means of developing the critical care knowledge, skills and practice in ward areas. It became apparent that education and training alone were insufficient to ensure that the aims of comprehensive critical care were realized. The way in which the nurses approached and organized their work and the availability of resources had a great impact on the ability of staff to care for these patients. It is argued that achieving comprehensive critical care is complex and that a multi-dimensional approach to the implementation of policy is essential in order to realize its aims.


The Language of Hidden Messages : A Study of the Patient's Latent Communication About the Therapeutic Relationship.
The patient in psychotherapy often communicates disguised impressions of the therapist. Certain mechanisms, such as displacement from the therapist to other persons and situations or identification with the therapist, contribute to disguising the communication. Among patients' manifest stories about relationships, those selected by two independent raters as latent communications about the therapist contained more negative aspects and destructive interactions than those not selected. In the nonselected stories the patient and his or her relationships were portrayed more positively. This may be a clue as to how therapists make assessments of whether latent content about the therapist is present. They may view it as more likely to be present if the patient speaks of negative feelings in relationships.


Assessment of zinc nutritional status in rural China.
Zinc nutriture was assessed in 6500 adults aged 35-64 years old in 65 mostly rural counties (two communes per county) in China on the basis of plasma zinc levels and dietary zinc intakes. In addition, the use of plasma albumin and red blood cell superoxide dismutase (SOD) for assessing zinc nutritional status was evaluated. Plasma levels of zinc and albumin were highly correlated between sexes (p<0.001) and between neighbouring communes in the same county (p<0.005), indicating a high degree of data reliability as assessed by this measure of "within county" homogeneity. Zinc deficiency, defined as plasma zinc values less than 70 μg/dL, was not observed for the populations in any of the 65 counties included in the survey. Dietary zinc intake was estimated on the basis of the newly revised Chinese food composition tables in conjunction with a 3-day household dietary survey of approximately 2000 households in the same study. Average dietary zinc intake was 11.9 mg/day, with a wide variability (7.4-34.9 mg/day) across the sample of 65 counties. The average levels of plasma zinc and dietary zinc intake observed in this adult rural Chinese population were comparable to those reported in healthy U.S. subjects, suggesting that zinc deficiency may not be a cause for concern in rural Chinese adults. However, marginal zinc deficiency may be prevalent in some rural areas.


Osteogenic sarcoma: a study of the ultrastructure.
Ultrastructural examination of 26 osteogenic sarcomas has revealed that in addition to the basic osteoblast comprising the tumor, five additional cell types may be identified. These include chondroblasts, osteocytes, undifferentiated cells and myofibroblasts. The latter cell type has not been reported in previous studies of medullary osteosarcomas. The relative portions of the cell types varied as to the type of osteogenic sarcoma studied. Osteoid production, the single diagnostic feature of these tumors, was evident and the various ultrastructural appearances of this material are shown. One case of an osteogenic sarcoma that arose in Paget's disease of bone is described and did not differ ultrastructurally from the conventional medullary osteogenic sarcoma. Our studies have shown that osteogenic sarcoma may share common ultrastructural features with other sarcomas involving bone and soft tissue and that the basic difference between osteogenic sarcoma and soft-tissue sarcomas is the presence of osteoid in the former and differing cytoplasmic differentiation in the latter category of tumors.


Transapical implantation of the SAPIEN 3 valve.
We report two cases of high-risk aortic stenosis treated with the SAPIEN 3 valve. This is the first procedure performed with this type of valve through the transapical approach. This new balloon-expandable valve incorporates a lower profile cobalt-chromium stent and an additional outer skirt to enhance paravalvular sealing. The procedure was performed without complications and no paravalvular leak was detected in control echocardiogram at follow-up.


Buried treasure: Unlocking the secrets of medicinal mushrooms.
In this issue of the Biomedical Journal, we investigate the potential of plants and fungi as a source of beneficial molecules for human health. We explore the weird and wonderful world of the mushroom and examine how Western medicine still has a lot to learn from Eastern practices dating back thousands of years. We also discuss a study further supporting claims that flaxseed, the plant kingdom's richest source of omega-3 fatty acids, can have lipid-lowering and fat-busting properties in the right physiological context. Finally, this issue also includes several validation studies of medical procedures or devices that define optimal conditions for their use in Asian populations.


Narrative Review of the objective analysis of long-term outcome of the Ponseti technique: experience from Dallas.
In 2001, Texas Scottish Rite Hospital for Children (TSRH) prospectively began a clubfoot database that included all of our patients with clubfeet who were willing to enroll. Nonoperative treatment, primarily the Ponseti method, was utilized. This article summarizes the experience from Dallas treating idiopathic clubfeet using the Ponseti technique, and is based on previously published studies utilizing information from the database. Patient clinical outcomes were defined as "good" (plantigrade foot achieved either with or without a percutaneous heel-cord tenotomy), "fair" (a plantigrade foot that required a limited procedure, such as tibialis anterior tendon transfer or posterior release), or "poor" (a plantigrade foot that required posteromedial release). Nearly 95% of idiopathic clubfeet obtained initial correction using the Ponseti technique, but relapses occurred and by age two years 24% needed some surgical intervention, usually limited procedures. Use of Dimeglio's rating system before treatment strongly correlated with the probability of a "good" outcome at two years. Objective measurements of brace wear compliance (iButton) in those who reached age two years with "good" outcomes demonstrated an unexpected pattern of diminishing use of the foot abduction orthoses over the first two years of brace wear. By the 18-month period of brace wear, 1/3 patients wore the orthoses less than 6 hours per day, and nearly half of the patients wore the orthoses less than 8 hours per day. Between ages 2-5 years, nearly 21% of the corrected clubfeet at age two years needed limited procedures to maintain/regain plantigrade positioning. Lateral weight-bearing radiographs between 18-24 months were not helpful in predicting future relapse in these patients, and are no longer routinely obtained. Following these patients for normal development is important, as nearly 9% of infants initially presenting as idiopathic clubfeet were eventually found to have another disorder including neurological, syndromic, chromosomal, or spinal abnormalities. We continue to emphasize the need to devote great attention to detail when using the Ponseti method in an effort to optimize the clinical outcomes.


Investigating Longitudinal Tobacco Use Information from Social History and Clinical Notes in the Electronic Health Record.
The electronic health record (EHR) provides an opportunity for improved use of clinical documentation including leveraging tobacco use information by clinicians and researchers. In this study, we investigated the content, consistency, and completeness of tobacco use data from structured and unstructured sources in the EHR. A natural language process (NLP) pipeline was utilized to extract details about tobacco use from clinical notes and free-text tobacco use comments within the social history module of an EHR system. We analyzed the consistency of tobacco use information within clinical notes, comments, and available structured fields for tobacco use. Our results indicate that structured fields for tobacco use alone may not be able to provide complete tobacco use information. While there was better consistency for some elements (e.g., status and type), inconsistencies were found particularly for temporal information. Further work is needed to improve tobacco use information integration from different parts of the EHR.


Laser-driven plasma waves in capillary tubes.
The excitation of plasma waves over a length of up to 8 cm is demonstrated using laser guiding of intense laser pulses through hydrogen-filled glass capillary tubes. The plasma waves are diagnosed by spectral analysis of the transmitted laser radiation. The dependence of the spectral redshift-measured as a function of filling pressure, capillary tube length, and incident laser energy-is in excellent agreement with simulation results. The longitudinal accelerating field inferred from the simulations is in the range of 1-10 GV/m.


Bone Diseases: Current Approach and Future Perspectives in Drug Delivery Systems for Bone Targeted Therapeutics.
Bone diseases include a wide group of skeletal-related disorders that cause mobility limitations and mortality. In some cases, e.g., in osteosarcoma (OS) and metastatic bone cancer, current treatments are not fully effective, mainly due to low patient compliance and to adverse side effects. To overcome these drawbacks, nanotechnology is currently under study as a potential strategy allowing specific drug release kinetics and enhancing bone regeneration. Polymers, ceramics, semiconductors, metals, and self-assembled molecular complexes are some of the most used nanoscale materials, although in most cases their surface properties need to be tuned by chemical or physical reactions. Among all, scaffolds, nanoparticles (NPs), cements, and hydrogels exhibit more advantages than drawbacks when compared to other nanosystems and are therefore the object of several studies. The aim of this review is to provide information about the current therapies of different bone diseases focusing the attention on new discoveries in the field of targeted delivery systems. The authors hope that this paper could help to pursue further directions about bone targeted nanosystems and their application for bone diseases and bone regeneration.


Extended preservation of rat liver graft by induction of heme oxygenase-1.
Livers can be preserved only for a short period without jeopardizing the transplantation outcome. Heat shock proteins (HSPs) protect against ischemia and reperfusion injury. We studied whether their induction and, in particular, the induction of heme oxygenase 1 (HO-1), improves transplantation survival after an extended time of cold storage. Rats were subjected to heat preconditioning (42 degrees C for 20 minutes). Livers were harvested 24 hours later, preserved in cold University of Wisconsin solution for 44 hours, and transplanted in isogeneic rats (arterialized transplantation). HO-1 was specifically induced and inhibited by cobalt protoporphyrin and tin protoporphyrin, respectively. All animals receiving a graft without preconditioning and subjected to 44 hours of cold preservation died within 3 days, whereas 89% of rats who received a graft exposed to heat survived for 3 weeks (P =.0004). Preconditioning reduced serum aspartate transaminase (AST) and lactate dehydrogenase activities after reperfusion, improved bile flow, and decreased the histologic lesions of reperfusion injury. These significant effects of heat preconditioning were prevented by administration of tin protoporphyrin and could be reproduced by administration of cobalt protoporphyrin. In grafts without preconditioning, only a small fraction (<5%) of hepatocytes were positive with the terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) assay, and even less expressed activated caspase 3. Preconditioning tended to reduce the number of positive cells and to stimulate the expression of antiapoptotic Bcl-X(L). In conclusion, heat preconditioning and, specifically, overexpression of HO-1 improve posttransplantation survival and graft function after prolonged cold ischemia preservation. The mechanism underlying these beneficial effects does not appear to be prevention of apoptosis.


Psychosocial interventions reduce cortisol in breast cancer patients: systematic review and meta-analysis.
Cancer initiation, progression and recurrence are intricate mechanisms that depend on various components: genetic, psychophysiological, or environmental. Exposure to chronic stress includes fear of recurrence that can affect biological processes that regulate immune and endocrine systems, increase cancer risk, and influence the survival rate. Previous studies show that psychological interventions might influence the level of cortisol that has been extensively used as a biomarker for measuring hypothalamic-pituitary-adrenal axis functioning and body's immunity response. This meta-analysis aimed to provide a quantitative scrutiny of the effect of certain types of psychosocial interventions on cortisol as a neuroendocrine biomarker in saliva or blood and might predict breast cancer (BC) progression. A literature search was performed in the following databases: PubMed, The Cohrane Library, Scopus, WOS, PsychInfo, Google Scholar, Ovid Science Direct. After methodical selection of originally generated 2.021 studies, the search yielded eight articles that met inclusion criteria. All these studies explored effects of psychosocial interventions that measured cortisol in total of 366 participants with BC, stages 0-IV, in randomized control trial or quasi experimental study design setting. We applied random effects model to conduct meta-analyses on the parameters of salivary and plasma cortisol and used PRISMA Guidelines as validated methodology of investigation to report the results. Eight studies selected for meta-analysis have shown the reduction of cortisol level due to applied psychosocial intervention. The random effects model showed that interventions produced large effect sizes in reductions of cortisol in blood (Cohen's d = -1.82, 95% Confidence Interval (CI): -3.03, -0.60) and slightly less in saliva (d = -1.73, 95%CI: -2.68, -0.78) with an overall effect of d = -1.76 (95%CI: -2.46, -1.07). Our study concluded that certain types of psychosocial interventions reduce cortisol (indicator of chronic stress) in patients with BC. Application of specific psychosocial support as adjuvant non-invasive therapy for affected females with BC at all phases of treatment could contribute to more cost-effective health care.


Direct Entry to 4,10-Didesmethyl (9S)-Dihydroerythronolide A via Catalytic Allene Osmylation.
Desmethyl erythronolides have emerged as macrolide targets that may prove effective against resistant bacteria. A five-step sequence to 4,10-didesmethyl (9S)-dihydroerythronolide A (1) from known cyclic bis[allene] 13 is reported. Key structural and mechanistic aspects of the synthesis are discussed along with catalytic allene osmylation. An improved route to 13 is also described.


Analgesic effect of novel organogermanium compound, GE-132.
A novel organogermanium compound, Ge-132, carboxyethylgermanium sesquioxide, showed enhancement of 0.5 mg/kg morphine analgesia in both administration routes of oral administration (p.o.) and intraperitoneal injection (i.p.) in the Tail-Flick test, and the effect was completely abolished by 0.5 mg/kg Naloxone, stereospecific opiate antagonist. Ge-132 alone, 250 mg/kg i.p., did not show any antinociceptive action by assessing the Tail-Flick test and the Hot-Plate test. By the intracerebral injection of Ge-132, 100-1000 micrograms, prolongation of Tail-Flick latency was observed and the action was abolished by 50 micrograms CaCl2 injection. Although bestatin which is reported to enhance the morphine analgesia inhibits enkephalinase and enkephalin aminopeptidase, Ge-132 did not show any inhibition on both enkephalin degrading enzymes. The possibility for the mode of action of Ge-132 was discussed.


Transthoracic device closure of perimembranous ventricular septal defect via a small left intercostal incision in children.
In children with perimembranous ventricular septal defect, surgical repair requires sternotomy and leaves unsightly scars, which can trigger long-term physical and psychological distress. However, transcatheter device closure is limited by vascular diameter, radiographic exposure, and expensive DSA equipment. We used an ultra-small left intercostal incision for transthoracic device closure to avoid the above problems and investigated its safety and feasibility by comparing it with surgical repair. This study enrolled 358 children with perimembranous ventricular septal defect. Among them, 152 patients were treated by surgical closure and 206 by transthoracic device closure via an ultra-small left intercostal incision. Perioperative clinical data and postoperative follow-up results were collected and analyzed retrospectively. The success rate was similar (P = 0.265) in the two groups: 203/206 patients in the device group vs. 152/152 patients in the surgical group. The operative time, intensive care unit time, mechanical ventilation time, and postoperative hospital stay were significantly shorter in the device group than in the surgical group. Although the incision length of the device group (1.1 ± 0.2 cm) was significant shorter (P < 0.001) than that of the surgical group (6.7 ± 1.5 cm), there was no difference in hospitalization costs between the two groups (P = 0.099). Except for small residual shunt (16/206 vs. 3/152, P = 0.017), the incidence of complications in the device group was lower or equal to that in the surgical group, and all small residual shunt disappeared during follow-up. There was no thoracic deformity in the device group, compared with 11 cases in the surgery group during follow-up (P < 0.001). Transthoracic device closure via an ultra-small left intercostal incision under transesophageal echocardiography guidance is safe and feasible. With appropriate indications, it can be a suitable alternative to surgical closure for treating perimembranous ventricular septal defect in children.


Enzyme immunoassay for serum antibody to Mycoplasma hominis in women with acute pelvic inflammatory disease.
A sensitive, four-layer modification of an enzyme immunoassay was developed for the determination of serum antibodies to Mycoplasma hominis. The suitability of the test for diagnostic use was studied with women who had acute pelvic inflammatory disease (PID). Twenty (23%) of 86 women with PID from whom paired sera were obtained demonstrated a significant change in levels of IgG antibody, a finding suggestive of recent infection with M. hominis. The occurrence of such change was not related to the isolation of Chlamydia trachomatis or Neisseria gonorrhoeae from the lower genital tract. Women with PID had significantly higher levels of IgG and IgA antibody to M. hominis, whereas the amount of IgM antibodies present did not differ between the groups. Levels of IgG antibody increased and those of IgM antibody decreased with increasing age. This change was found both among women with PID and among controls.


Disturbed flow in an aquatic environment may create a sensory refuge for aggregated prey.
Predators use olfactory cues moved within water and air to locate prey. Because prey aggregations may produce more cue and be easier to detect, predation could limit aggregation size. However, disturbance in the flow may diminish the reliability of odour as a prey cue, impeding predator foraging success and efficiency. We explore how different cue concentrations (as a proxy for prey group size) affect risk to prey by fish predators in disturbed (more turbulent or mixed) and non-disturbed (less mixed) flowing water. We find that increasing odour cue concentration increases predation risk and disturbing the flow reduces predation risk. At high cue concentration fish were able to locate the cue source in both disturbed and non-disturbed flow, but at medium concentrations, predators only located the cue source more often than expected by chance in non-disturbed flow. This suggests that objects disturbing flow provide a sensory refuge allowing prey to form larger groups, but that group sizes may be limited by level of disturbance to the flow.


Live Imaging of the Dehydration Effect of Isosorbide on the Normal and Hydropic Guinea Pig Cochleae Using Optical Coherence Tomography.
To investigate the isosorbide-induced dehydration effect on the endolymphatic space by intratympanic administration of isosorbide. Isosorbide, an osmotic diuretic, is used orally as a typical conservative therapy for Menière's disease (MD) in Japan. The dehydration effect occurs 6 hours after isosorbide ingestion. Intratympanic administration of isosorbide resolves endolymphatic hydrops faster than oral ingestion. In addition, the dehydration effect has never been shown directly. Therefore, we investigated the dehydration effect of intratympanic administration of isosorbide on endolymphatic hydrops using optical coherence tomography. We used eight Hartley guinea pigs, divided into normal and hydrops groups. In the hydrops group, the animals underwent endolymphatic sac obliteration to create endolymphatic hydrops. We obtained midmodiolar section images of the cochleae using optical coherence tomography. Then, 50 to 70% isosorbide was sequentially administered intratympanically for 5 minutes, and the apical turn of the cochlea was observed. The relative midmodiolar cross-sectional area of the scala media was calculated for quantitative assessment of the endolymphatic space. In the normal group, 50% isosorbide had a slight but significant dehydration effect on the scala media; at 55 to 70%, Reissner's membrane became flat. In the hydrops group, 50% isosorbide slightly reduced endolymphatic hydrops; 65% flattened Reissner's membrane, and 70% slightly concaved it toward the basilar membrane. The results suggest that we could select the concentration of isosorbide according to the stage or severity of MD and relief from acute attack. Intratympanic administration of isosorbide may be a promising treatment for patients with MD.


Autoimmune thyroid disease in pregnant women and their offspring.
To present an overview of autoimmune thyroid disease (AITD) that can occur in pregnancy. The major thyroid antibodies that can traverse the maternal-fetal circulation and affect the fetus are summarized, those women at risk of having affected fetuses are identified, and the diagnosis, course, and treatment of AITD in maternal and neonatal patients are discussed. AITD, including Graves' disease and autoimmune thyroiditis, is common in women of childbearing age. Rarely, the fetus can be affected because of transplacental passage of maternal IgG. Of the thyroid autoantibodies found in AITD, only those directed against the thyroid-stimulating hormone (TSH) receptor have been shown to cause fetal thyroid dysfunction. Both transient neonatal hyperthyroidism and hypothyroidism have been described, as has delayed onset of neonatal hyperthyroidism due to the coexistence of stimulating and blocking TSH receptor antibodies. In general, affected infants are those born to mothers with the most potent antibody activity, and the duration of the neonatal thyroid dysfunction is dependent on the antibody titer and the rate of metabolic clearance from the infant's circulation. If fetal hyperthyroidism is suspected, maternal TSH receptor antibodies should be measured during the third trimester of pregnancy. For neonatal hypothyroidism, this measurement in the mother or baby soon after birth will suffice. Screening for the presence of TSH receptor antibodies by radioreceptor assay is the most cost-effective approach. If results are positive, bioassay should be done to determine the nature of the antibody activity. Women at risk of having babies with neonatal hyperthyroidism include those with a history of previous affected infants, with difficult to control thyrotoxicosis, or with a history of Graves' disease and development of hypothyroidism either spontaneously or as a result of thyroid gland ablation. Transient neonatal hypothyroidism due to TSH receptor-blocking antibodies should be suspected in any infant with hypothyroidism born to a mother with AITD (particularly those with previously affected offspring). Treatment of maternal hyperthyroidism must consider both maternal and fetal thyroid status. In general, the lowest dose of antithyroid medication sufficient to produce maternal euthyroidism or slight hyperthyroidism is used. In pregnant women with hypothyroidism, doses of L-thyroxine should be sufficient to normalize maternal thyroid function without regard to the fetus. Identification and treatment of affected infants soon after birth will ensure a normal outcome. Whether inadequately treated maternal hypothyroidism is associated with a permanent intellectual deficit in the offspring is currently unknown.


Neurolytic celiac plexus block: a better alternative to opioid treatment in upper abdominal malignancies: an Indian experience.
The majority of patients with advanced upper abdominal malignancies suffer from moderate to severe pain due to unavailability of morphine in developing world. This study was undertaken to evaluate the role of neurolytic celiac plexus block on pain and quality of life in this patient subpopulation. One hundred consecutive patients receiving opioids for their pain relief were divided in two groups. Group I (control) patients received oral morphine & NSAIDS and group II (study) patients underwent neurolytic celiac plexus block (NCPB) to compare their effects on pain relief, morphine consumption, quality of life (QOL), Karnofsky and performance scores up to one month. NCPB provided statistically significant better pain relief and reduced morphine consumption at one month (P = 0.000). Superior Karnofsky and performance scores also favored NCPB group (P = 0.000); however the difference in overall QOL was not statistically significant (P = 0.24). Patients in oral morphine group had more side effects (94% vs. 58%) as compared to NCPB (P = 0.000). NCPB is an effective tool to reduce opioid requirement and the drug-related adverse effects. It is a rewarding technique, especially when morphine availability and its easy accessibility to the deserving patient is poor.


Exploring the Relationship Between Interpersonal Emotion Regulation and Social Anxiety Symptoms: The Mediating Role of Negative Mood Regulation Expectancies.
This study aimed to investigate the relationship between interpersonal emotion regulation (IER) and social anxiety symptoms and the mediating role of negative mood regulation expectancies (NMRE). We hypothesised that IER is positively associated with social anxiety symptoms, controlling for depression and intrapersonal emotion regulation strategies of suppression and reappraisal, and NMRE mediate this relationship. Study 1 was conducted with a student sample (N = 400) and Study 2 included a community sample with 271 participants. Study 1 showed that, of four IER strategies, soothing and social modeling were positively, and perspective-taking was negatively related to social anxiety symptoms controlling for depression, suppression and reappraisal. Study 2 replicated these findings and extended them by showing the mediated relationship between the two IER strategies (i.e. enhancing positive affect and soothing) and social anxiety symptoms through NMRE. The results contribute to the limited research on IER by portraying its relationship with social anxiety symptoms and revealing the mediating role of NMRE in this relationship.


Differences in nitric oxide production by superficial and deep human articular chondrocytes: implications for proteoglycan turnover in inflammatory joint diseases.
During inflammatory joint diseases, chondrocytes are exposed to cytokines such as IL-1 that induce the synthesis of nitric oxide (NO). Chondrocytes from different zones of the articular cartilage are known to have different metabolic properties. In the present study, we have demonstrated that chondrocytes recovered from the superficial zone of normal, human, articular cartilage synthesize approximately 2 to 3 times as much NO in response to IL-1 as chondrocytes recovered from the deep zone of the same cartilage. Production of NO by normal cartilage in response to IL-1 was also found to decrease with age. Addition of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMA, 1 mM) blocked NO production by cells of both zones. L-NMA completely reversed the suppression of proteoglycan synthesis imposed by IL-1 in deep chondrocytes, but produced only partial reversal in superficial cells. As noted previously, IL-1 failed to elicit a strong catabolic response in cultures of human cartilage. In the presence of L-NMA, however, IL-1 reduced the metabolic t(1/2) of proteoglycans by approximately 50% in both the superficial and deep zones. This suggests that NO has, directly or indirectly, an anticatabolic effect in human cartilage. These data confirm the metabolic heterogeneity of human chondrocytes, and suggest that NO may be involved to different degrees as an endogenous modulator of the turnover of the cartilaginous matrix in different zones of articular cartilage.


Identification of floR Variants Associated With a Novel Tn4371-Like Integrative and Conjugative Element in Clinical Pseudomonas aeruginosa Isolates.
Florfenicol is widely used to control respiratory diseases and intestinal infections in food animals. However, there are increasing reports about florfenicol resistance of various clinical pathogens. floR is a key resistance gene that mediates resistance to florfenicol and could spread among different bacteria. Here, we investigated the prevalence of floR in 430 Pseudomonas aeruginosa isolates from human clinical samples and identified three types of floR genes (designated floR, floR-T1 and floR-T2) in these isolates, with floR-T1 the most prevalent (5.3%, 23/430). FloR-T2 was a novel floR variant identified in this study, and exhibited less identity with other FloR proteins than FloRv. Moreover, floR-T1 and floR-T2 identified in P. aeruginosa strain TL1285 were functionally active and located on multi-drug resistance region of a novel incomplete Tn4371-like integrative and conjugative elements (ICE) in the chromosome. The expression of the two floR variants could be induced by florfenicol or chloramphenicol. These results indicated that the two floR variants played an essential role in the host's resistance to amphenicol and the spreading of these floR variants might be related with the Tn4371 family ICE.


A prediction model for COPD readmissions: catching up, catching our breath, and improving a national problem.
Frequent COPD exacerbations have a large impact on morbidity, mortality and health-care expenditures. By 2020, the World Health Organization expects COPD and COPD exacerbations to be the third leading cause of death world-wide. Furthermore, In 2005 it was estimated that COPD exacerbations cost the U.S. health-care system 38 billion dollars. Studies attempting to determine factors related to COPD readmissions are still very limited. Moreover, few have used a organized machine-learning, sensitivity analysis approach, such as a Random Forest (RF) statistical model, to analyze this problem. This study utilized the RF machine learning algorithm to determine factors that predict risk for multiple COPD exacerbations in a single year. This was a retrospective study with a data set of 106 patients. These patients were divided randomly into training (80%) and validating (20%) data-sets, 100 times, using approximately sixty variables intially, which in prior studies had been found to be associated with patient readmission for COPD exacerbation. In an interactive manner, an RF model was created using the training set and validated on the testing dataset. Mean area-under-curve (AUC) statistics, sensitivity, specificity, and negative/positive predictive values (NPV, PPV) were calculated for the 100 runs. THE FOLLOWING VARIABLES WERE FOUND TO BE IMPORTANT PREDICTORS OF PATIENTS HAVING AT LEAST TWO COPD EXACERBATIONS WITHIN ONE YEAR: employment, body mass index, number of previous surgeries, administration of azithromycin/ceftriaxone/moxifloxacin, and admission albumin level. The mean AUC was 0.72, sensitivity of 0.75, specificity of 0.56, PPV of 0.7 and NPV of 0.63. Histograms were used to confirm consistent accuracy. The RF design has consistently demonstrated encouraging results. We expect to validate our results on new patient groups and improve accuracy by increasing our training dataset. We hope that identifying patients at risk for frequent readmissions will improve patient outcome and save valuable hospital resources.


Perforation of jejunal non Hodgkin's lymphoma.
Primary gastrointestinal lymphomas are rare. Jejunal non Hodgkin's lymphoma presenting as perforative peritonitis is extremely rare. We report a 51-year-old man who presented with perforative peritonitis and was detected to have jejunal non Hodgkin's lymphoma. He was treated with resection of the affected segment with its mesentery and postoperative chemotherapy, and was asymptomatic 5 months later.


Characterization of Vancomycin-Resistant Enterococcus faecalis and Enterococcus faecium Isolated from Fresh Produces and Human Fecal Samples.
Increased enterococcal infections in hospitals and multidrug-resistant and vancomycin-resistant enterococci (VRE) isolated from humans, animals, and food sources raised public health concern on the presence of VRE in multiple sources. We performed a comparative analysis of the antimicrobial resistance and genetics of VRE isolates derived from fresh produce and human fecal samples. Of 389 Enterococcus isolates, 8 fecal and 3 produce isolates were resistant to vancomycin and teicoplanin; all harbored vanA gene. The VRE isolates showed multidrug-resistant properties. The isolates from fresh produce in this study showed to have the common shared characteristics with the isolates from humans by the results of antimicrobial resistance, multilocus sequence typing, and Tn 1546 transposon analysis. Therefore, VRE isolates from fresh produce are likely related to VRE derived from humans. The results suggested that VRE may contaminate vegetables through the environment, and the contaminated vegetables could then act as a vehicle for human infections. Ongoing nationwide surveillance of antibiotic resistance and the promotion of the proper use of antibiotics are necessary.


Conditioned abstinence in alcoholics: a controlled experiment.
The existence of conditioned abstinence symptoms in 16 abstinent alcoholics was investigated by comparing their subjective, physiological, and behavioral responses while viewing slides of alcohol-related and non-alcohol-related stimuli. The alcoholics were randomly assigned to one of two groups. The first group viewed a set of six alcohol-related slides the first day and a set of six non-alcohol-related slides the following day. The second group looked at the same slides, but the order of presentation was reversed. Alcohol-related slides produced significantly greater increases in subjectively reported alcohol craving and anxiety scores. There were no differences between the two sets with regard to physiological measures or subjective reports of heart rate. The global observations showed significant differences between the alcohol-related and non-alcohol-related slides.


Regeneration of the epidermis and mucosal epithelium on the basement membranes.
The processes of degeneration and regeneration of the lip epidermis and mucosal epithelium after cryo treatment were observed by transmission electron microscopy. Epidermal and mucosal epithelial cells degenerated due to the formation of ice crystals and detached from the basement membranes, leaving a small amount of cell debris. Regenerating cells migrated over the cell debris, which was gradually phagocitized, and formed new hemidesmosomes with the preexisting lamina densa. Regenerating epidermal cells migrated from the undamaged areas and the hair follicles. Regenerating mucosal epithelial cells originated from surviving cells in the basal half of the epithelium, at the periphery of the blister cavity. They migrated in a multilayered fashion. Desmosomes were preserved even between dead cells and between dead and living cells.


Effect of dietary soluble fiber on neurohormonal profiles in serum and brain of rats.
This study was conducted to investigate the effect of dietary soluble fiber administration and /or high fat diet on serum and brain neurohormonal profiles, adipose tissue mass and body weight gain in Sprague-Dawley rats. Four groups of rats were respectively fed 10% fat diet (C), 10% fat plus pectin diet (P), 20% fat diet (HFC) and 20% fat plus pectin diet (HFP) for 4 weeks. In HFP group, the food and energy intake, body weight gain, FER including fecal excretion were the smallest (p<0.05). Serum HDL-cholesterol, triglyceride and glucose level were also the lowest in HFP group (p<0.05). The weight of brain, epididymal fat pad and adrenal gland except liver didn't show any significant differences among groups. Interestingly serum norepinephrine concentration of HFP group tended to be higher, but dopamine concentration tended to be lower than those of HFC group. However serum catecholamine concentration didn't show any significant differences among all groups. Norepinephrine and epinephrine contents of right portion of midbrain of P and HFP groups were remarkably lower than those of the C group. These results suggested that soluble fiber pectin consumption might affect neurohormonal profiles in serum and brain according to dietary fat level.


Upper arm polytetrafluoroethylene grafts for dialysis access. Analysis of two different graft sizes: 6 mm and 6-8 mm.
The purpose of this retrospective study was to analyze 2 sizes of expanded polytetrafluoroethylene (PTFE) upper arm grafts for dialysis: 8 millimeters, tapered to 6 mm at the arterial side, and 6 millimeters. All upper arm PTFE grafts (Gore-Tex(R)) were performed between January 1981 and April 1997. Patient characteristics, complication rate, and patency rates were compared for both kind of grafts. Five hundred and seven PTFE grafts were analyzed (183 6-mm grafts and 324 6- to 8-mm grafts). Early failure was found in 5 grafts (2.7%) in 6-mm grafts, and in 5 grafts (1.5%) in 8-mm grafts (not significant). Steal syndrome was found in 1 patient (0.5%) of the 6-mm group, and in 11 (3.4%) of the 8-mm grafts (p=0.085). The rate of late complications requiring surgical repair was 0.56 episode per graft-year in the 6-mm grafts group, and 0.33 in the 8-mm grafts (p<0.001). Primary patency rates of 6-mm grafts were 72%, 33%, and 19% at 1, 3, and 5 years; and secondary patency rates were 86%, 68%, 56%, and 44% at 1, 3, 5, and 6 years, respectively. In the 8-mm grafts group, primary patency rates were 77%, 52%, and 39% at 1, 3, and 5 years; and secondary patency rates were 92%, 84%, 73%, and 66% at 1, 3, 5, and 6 years, respectively. Comparison of patency rates of 6-mm and 8-mm grafts were statistically significant (p<0.001) for both primary and secondary curves. However, secondary survival curves were similar for both kind of grafts in a subpopulation of diabetic patients. The authors conclude that the 8-mm graft, tapered to 6 mm at the arterial side, is a dialysis graft with fewer complications and a better patency rate than grafts of 6 mm placed in the same anatomical position, at least in a population of nondiabetic patients. Steal syndrome was observed in some cases of diabetic and older patients with a large-bore graft. Thus, this kind of prosthesis should be avoided in this population. On the other hand, this is not a prospective, randomized study made with any intention for comparison. Therefore, the aforementioned conclusions must be cautiously considered.


BNP and congestive heart failure.
Brain natriuretic peptide (BNP), a peptide hormone secreted chiefly by ventricular myocytes, plays a key role in volume homeostasis. The plasma concentration of BNP is raised in various pathological states, especially heart failure. Many studies suggest that measurement of plasma BNP has clinical utility for excluding a diagnosis of heart failure in patients with dyspnea or fluid retention and for providing prognostic information in those with heart failure or other cardiac disease. It may also be of value in identifying patients after myocardial infarction in whom further assessment of cardiac function is likely to be worthwhile. Preliminary evidence suggests that measuring the plasma concentration of BNP may be useful in fine tuning therapy for heart failure. Artificially raising the circulating levels of BNP shows considerable promise as a treatment for heart failure. With simpler assay methods now available, it is likely that many physicians will measure plasma BNP to aid them in the diagnosis, risk stratification, and monitoring of their patients with heart failure or other cardiac dysfunction.


Asymmetric total synthesis of a pentacyclic Lycopodium alkaloid: huperzine-Q.
Right on Q: the first asymmetric total synthesis of (-)-huperzine-Q, which possesses six stereogenic centers and a spiroaminal moiety, has been achieved in 19 steps and 16.4 % overall yield. This synthesis involved a novel stereoselective Pauson-Khand reaction, a vinyl Claisen rearrangement, and a biomimetic spiroaminal formation. TBDPS=tert-butyldiphenylsilyl.


Assembly of nanosize metallic particles and molecular wires on electrode surfaces.
This article highlights recent developments in the assembly of nanosize materials on electrode surfaces. A brief historical background of the field is given, followed by a selection of topics of particular current interest. We focus especially on the assembly of nanosize metallic particles and molecular wires on gold and silicon electrode surfaces. The fabrication, properties, and characteristics of functional nanostructured biointerfaces on electrode surfaces are also described.


Review of Dilaceration of Maxillary Central Incisor: A Mutidisciplinary Challenge.
Traumatic injuries to primary dentition may interfere with the development of permanent dentition. Among the many malformations, dilaceration is particularly important to the clinician. Management of dilacerated maxillary central incisor requires a multidisciplinary approach. The main purpose of this review is to present the etiological factors, the mechanism, clinical features, radiographic features and treatment of dilaceration of the maxillary central incisors. How to cite this article: Walia PS, Rohilla AK, Choudhary S, Kaur R. Review of Dilaceration of Maxillary Central Incisor: A Multidisciplinary Challenge. Int J Clin Pediatr Dent 2016;9(1):90-98.


Therapeutic effects of 7- to 14-day subanesthetic ketamine infusions for chronic pain on standardized psychiatric measures.
Background: We have previously shown that subanesthetic ketamine infusions effectively reduce refractory pain. However, the effects of ketamine infusions on comorbid conditions of depression and anxiety have not been explored in this patient population. Methods: We investigated the effects of ketamine on mood and anxiety in patients with refractory chronic pain treated with 7-14 days of subanesthetic continuous intravenous ketamine infusions, using well-validated clinical scales. Results: There was a significant 52% reduction in pain severity and 33% reduction in pain interference scores following ketamine treatment. Ketamine treatment also reduced scores on the depression module of the Patient Health Questionnaire (PHQ-9) by 28% and scores on the Generalised Anxiety and Depression Assessment (GAD-7) by 36%. Conclusion: Multiday subanesthetic ketamine infusions effectively reduce pain, anxiety and depression in patients with complex chronic pain.


A new species of Rana from the Dabie Mountains in eastern China (Anura, Ranidae).
A new species Rana dabieshanensissp. n. is described from the Dabie Mountains in Anhui Province, China, based on morphological character differences and molecular analyses. The new species can be distinguished from its congeners by a combination of diagnostic characters. The results of phylogenetic analyses (based on 12s rRNA, 16s rRNA, ND2, Cyt b, RAG1, BDNF and Tyr) and genetic distances (based on Cyt b) indicate that the new species belongs to the Rana longicrus group, and is placed as the sister taxon to R. hanluica.


Management of Neurofibromatosis of the Nipple-Areolar Complex.
Neurofibromatosis type 1 is an autosomal dominant disease having an incidence of 1 in 3000 individuals. It primarily involves the peripheral nervous system and usually presents with many neurofibromas. On rare occasions, NF1 can affect the breast and manifests as nipple-areolar complex extranipple (pseudopolythelia) like neurofibromas which can be disfiguring and sometimes cause pain and therefore need to be addressed surgically. We present a case of a 31-year-old female, who had multiple pedunculated neurofibromas around the nipple on both breasts for 3 years. These lesions were associated with mild pain and were increasing in size. Surgical excision was done while preserving the nipples bilaterally. NF1 primarily involves the peripheral nervous system and usually presents with a large number of neurofibromas. Several case series of patients with NF1 have been reported, but there are only a few published reports on neurofibromas of the nipple-areolar complexes. These lesions can be painful and cause cosmetic deformity. In our case, these lesions were approached by circumferentially excising the redundant nipple-areolar skin containing the neurofibromas, while isolating the nipple on a central ductal and vascular pedicle. In conclusion, the redundant nipple-areolar skin containing the neurofibromas can simply be approached by circumferential excision while preserving the nipple. This technique is simple, easy to perform, while it allows duct preservation and preserves cosmesis.


The basic helix-loop-helix factor Hand 2 regulates autonomic nervous system development.
Mammalian autonomic nervous system (ANS) development requires the combinatorial action of a number of transcription factors, which include Mash 1, Phox 2b, and GATA 3. Here we show that the bHLH transcription factor, Hand 2 (dHAND), is expressed concurrently with Mash 1 during sympathetic nervous system (SNS) development and that the expression of Hand 2 is not dependent on Mash 1. This suggests that these two bHLH factors work in parallel during SNS development. We also show that ectopic expression of Hand 2 activates the neuronal program and promotes the acquisition of a phenotype corresponding to peripheral neurons including neurons of the SNS lineage in P19 embryonic carcinoma cells. We propose that Hand 2 works in parallel with other members of the transcriptional network to regulate ANS developmental but can ectopically activate the program by a cross-regulatory mechanism that includes the activation of Mash 1. We show that this function is dependent on its interaction with the histone acetyltransferase p300/CBP, indicating that Hand 2 functions to promote ANS development as part of a larger transcriptional complex.


Development of a photolytic artificial lung: preliminary concept validation.
There is an established need for pulmonary technology capable of facilitated gas exchange in the blood, thereby bypassing the alveolar-capillary interface. To address this need, we emulated one of the best-known photolytic reactions in nature, photosynthesis, in which green plants use sunlight to drive the exchange of oxygen for carbon dioxide. Our goal in the current study was to demonstrate the feasibility of direct photolytic conversion of water to liquid phase oxygen (dissolved oxygen [DO]) in synthetic serum. To this end, we constructed a test flow cell consisting of a conductive coating of vacuum-deposited titanium (Ti) metal, adherent TiO2 (anatase), and MnO2, applied as a laminate to a glass substrate, and then immersed the device in Locke's-Ringer solution (synthetic blood serum). Long wavelength (low energy) ultraviolet A laser light, directed to the transparent glass slide, reproducibly resulted in the generation of an active form of oxygen (AO), which was subsequently converted directly by the catalytic action of MnO2 to DO. The absence of light activation provided an entirely null response. We conclude that the photolytic production of DO from water in a blood serum surrogate, with commensurate CO2 clearance, is feasible. A prototype photolytic module is proposed, which uses multiple parallel photolytic surfaces to improve system production capacity and CO2 clearance through selective gas-liquid separation from the oxygen-enriched fluid.


Impact of e-cigarette vaping aerosol exposure in pregnancy on mTOR signaling in rat fetal hippocampus.
Electronic cigarette (e-cig) use during pregnancy has become a major health concern in recent years and many view them as less harmful and may help quit or reduce combustible cigarettes. Implementing a state-of-the-art engineered vaping system, comprising an atomizer similar to those sold in vape shops, we aimed to utilize a translational e-cig inhalation delivery method to provide crucial information on the impact of prenatal e-cig aerosols on the developing brain hippocampal mTOR system in a rat model system. Gestational e-cig vaping significantly increased P-mTOR levels (p < 0.05) in the rat fetal hippocampi in the nicotine group (comprising of VG/PG + nicotine) compared to the control and the juice (comprising of VG/PG) groups. Total mTOR expression was not different among groups. Immunofluorescence imaging demonstrated P-mTOR was detected exclusively in the granule cells of the dentate gyrus of the fetal hippocampus. E-cig did not alter DEPTOR, but RAPTOR and RICTOR were higher (p < 0.05) in the Nicotine group. Gestational e-cig vaping with nicotine increased (p < 0.05) the activity and expression of 4EBP1, p70S6K, but decreased (p < 0.05) P-PKCα in the fetal hippocampi. In summary, dysregulation of mTORC1 and the related mTORC2, their activity, and downstream proteins together may play a critical role in e-cig-vaping-induced neurobiological phenotypes during development.


The potential of magnetic heating for fabricating Pickering-emulsion-based capsules.
Pickering emulsions (particle-stabilized emulsions) have been widely explored due to their potential applications, one of which is using them as precursors for the formation of colloidal capsules that could be utilized in, among others, the pharmacy and food industries. Here, we present a novel approach to fabricating such colloidal capsules by using heating in the alternating magnetic field. When exposed to the alternating magnetic field, magnetic particles, owing to the hysteresis and/or relaxation losses, become sources of nano- and micro-heating that can significantly increase the temperature of the colloidal system. This temperature rise was evaluated in oil-in-oil Pickering emulsions stabilized by both magnetite and polystyrene particles. When a sample reached high enough temperature, particle fusion caused by glass transition of polystyrene was observed on surfaces of colloidal droplets. Oil droplets covered with shells of fused polystyrene particles were proved to be less susceptible to external stress, which can be evidence of the successful formation of capsules from Pickering emulsion droplets as templates.


Transcriptional profiling identifies the long noncoding RNA plasmacytoma variant translocation (PVT1) as a novel regulator of the asthmatic phenotype in human airway smooth muscle.
The mechanism underlying nonsevere and severe asthma remains unclear, although it is commonly associated with increased airway smooth muscle (ASM) mass. Long noncoding RNAs (lncRNAs) are known to be important in regulating healthy primary airway smooth muscle cells (ASMCs), whereas changed expression has been observed in CD8 T cells from patients with severe asthma. Primary ASMCs were isolated from healthy subjects (n = 9) and patients classified as having nonsevere (n = 9) or severe (n = 9) asthma. ASMCs were exposed to dexamethasone and FCS. mRNA and lncRNA expression was measured by using a microarray and quantitative real-time PCR. Bioinformatic analysis was used to examine relevant biological pathways. Finally, the lncRNA plasmacytoma variant translocation 1 (PVT1) was inhibited by transfection of primary ASMCs with small interfering RNAs, and the effect on ASMC phenotype was examined. The mRNA expression profile was significantly different between patient groups after exposure to dexamethasone and FCS, and these were associated with biological pathways that might be relevant to the pathogenesis of asthma, including cellular proliferation and pathways associated with glucocorticoid activity. We also observed a significant change in lncRNA expression, yet the expression of only one lncRNA (PVT1) is decreased in patients with corticosteroid-sensitive nonsevere asthma and increased in patients with corticosteroid-insensitive severe asthma. Subsequent targeting studies demonstrated the importance of this lncRNA in controlling both proliferation and IL-6 release in ASMCs from patients with severe asthma. lncRNAs are associated with the aberrant phenotype observed in ASMCs from asthmatic patients. Targeting PVT1 might be effective in reducing airway remodeling in asthmatic patients.


Differences in compliance patterns across the selective serotonin reuptake inhibitors (SSRIs).
To evaluate differential compliance rates between immediate-release (IR) selective serotonin reuptake inhibitors (SSRI) and a controlled-release (CR) SSRI in patients initiating SSRI therapy. A retrospective analysis of patients initiating treatment with SSRIs identified in the IHCIS National Managed Care Database between July 2001 and December 2002 was conducted. Logistic regression models were used to assess differences in 6-month compliance rates, controlling for age, gender, utilization of mental health specialty care services, titration rates, diagnoses, and comorbidities. Compliance was defined as having a minimum medication possession ratio of 80% over a 180-day period without evidence of a 15-day gap prior to 90 days of therapy. There were 116 090 patients included in the study, with approximately 4% receiving a CR SSRI and 96% receiving IR SSRIs. Approximately 25% of patients had a diagnosis for depression, 16% had a diagnosis for anxiety, and 13% had a 16% had a diagnosis for anxiety, and 13% had a diagnosis for both anxiety and depression. Overall, diagnosis for both anxiety and depression. Overall, 54.2% were noncompliant with therapy, while 30.2% of patients were compliant with therapy, and 15.7% had evidence of a therapy change. After controlling for baseline covariates, patients initiating IR SSRIs were 14% less likely to be compliant compared to those initiating paroxetine CR (p < 0.0001). Patients initiating on paroxetine IR were least likely to be compliant (odds ratio [OR] 0.788; p < 0.0001), followed by escitalopram (OR 0.850; p = 0.0179), sertraline (OR 0.877; p = 0.0005), citalopram (0.909; p = 0.0114), and fluoxetine (OR 0.916; p = 0.0250). Approximately 54% of patients initiating SSRI therapy were noncompliant with SSRI therapy over a 6-month period, with the lowest level of compliance found in patients receiving IR SSRI agents. Future studies should assess the effect of compliance on economic measures and determine if reductions in resource utilization are found across specific SSRI agents.


Levels of medical care in the global war on terrorism.
Trauma care for military personnel injured in Iraq has become increasingly sophisticated. There are five levels, or echelons, of care, each progressively more advanced. Level I care provides immediate first aid at the front line. Level II care consists of surgical resuscitation provided by highly mobile forward surgical teams that directly support combatant units in the field. Level III care is provided through combat support hospitals--large facilities that take time to become fully operational but offer much more advanced medical, surgical, and trauma care, similar to a civilian trauma center. Level IV care is the first echelon at which definitive surgical management is provided outside the combat zone. Level V care is the final stage of evacuation to one of the major military centers in the United States, where definitive stabilization, reconstruction, or amputation of the injured extremity is performed.


Poloxamine 1107 sealing of radiopermeabilized erythrocyte membranes.
Lipid peroxidation-mediated permeabilization of cell membranes following intense ionizing irradiation is well documented. This form of membrane radiopermeabilization leads to rapid exhaustion of cellular high-energy compounds, resulting in the acute onset of cellular necrosis. Strategies to reverse the process of necrosis and preserve cell viability require membrane sealing. This report documents the relative efficacy of Poloxamine 1107, a non-ionic surfactant, compared with other polymers, in sealing radiopermeabilized cell membranes. Isolated erythrocytes were exposed to 600 Gy 60Co irradiation at a dose rate of 1.3 Gy/s. Different polymer compounds were added 10 min later to the irradiated cell suspensions. At 2 h later the haemoglobin content in the supernatants was determined spectrophotometrically. Compared with the non-treated irradiated control, Poloxamine 1107 significantly reduced the leakage of haemoglobin from irradiated erythrocytes. Poloxamer 188 and dextran at equal concentrations had no significant reverse effect on the irradiation-mediated increased membrane permeability. The amount of haemoglobin released from irradiated erythrocytes was inversely related to the Poloxamine 1107 concentration. This study demonstrates the capability of Poloxamine 1107 to seal radiopermeabilized cell membranes. Thus, surfactants such as Poloxamine 1107 might be useful as a therapeutic agent in the treatment of high-dose radiation injuries since cellular necrosis due to metabolic exhaustion following radiopermeabilization of their membranes might be prevented.


Fish viruses serologic comparison of the golden shiner and infectious pancreatic necrosis viruses.
High titer neutralizing antiserum to golden shiner virus (GSV) was produced in a rabbit. The GSV antiserum had significant neutralization indices in tests with the original strain of GSV and with another more recent isolate. Neutralization indices were not significant when two strains of infectious pancreatic necrosis virus (IPNV) were reacted with GSV antiserum, and neither isolate of GSV showed significant reactivity in neutralization tests with polyvalent IPNV antiserum. Our results indicate that IPNV and GSV are serologically unrelated.


Structure-activity studies on anticonvulsant sugar sulfamates related to topiramate. Enhanced potency with cyclic sulfate derivatives.
We have explored the structure-activity relationship (SAR) surrounding the clinically efficacious antiepileptic drug topiramate (1), a unique sugar sulfamate anticonvulsant that was discovered in our laboratories. Systematic structural modification of the parent compound was directed to identifying potent anticonvulsants with a long duration of action and a favorable neurotoxicity index. In this context, we have probed the pharmacological importance of several molecular features: (1) the sulfamate group (6-8, 22-25, 27, 84), (2) the linker between the sulfamate group and the pyran ring (9, 10, 21a,b), (3) the substituents on the 2,3- (58-60, 85, 86) and 4, 5-fused (30-38, 43, 45-47, 52, 53) 1,3-dioxolane rings, (4) the constitution of the 4,5-fused 1,3-dioxolane ring (2, 54, 55, 63-68, 76, 77, 80, 83a-r, 84-87, 90a, 91a, 93a), (5) the ring oxygen atoms (95, 96, 100-102, 104, 105), and (6) the absolute stereochemistry (106 and 107). We established the C1 configuration as R for the predominant alcohol diastereomer from the highly selective addition of methylmagnesium bromide to aldehyde 15 (16:1 ratio) by single-crystal X-ray analysis of the major diastereomer of sulfamate 21a. Details for the stereoselective syntheses of the hydrindane carbocyclic analogues 95, 96, 100, and 104 are presented. We also report the synthesis of cyclic imidosulfites 90a and 93a, and imidosulfate 91a, which are rare examples in the class of such five-membered-ring sulfur species. Imidosulfite 93a required the preparation and use of the novel sulfur dichloride reagent, BocN=SCl2. Our SAR investigation led to the impressive 4,5-cyclic sulfate analogue 2 (RWJ-37947), which exhibits potent anticonvulsant activity in the maximal electroshock seizure (MES) test (ca. 8 times greater than 1 in mice at 4 h, ED50 = 6.3 mg/kg; ca. 15 times greater than 1 in rats at 8 h, ED50 = 1.0 mg/kg) with a long duration of action (>24 h in mice and rats, po) and very low neurotoxicity (TD50 value of >1000 mg/kg at 2 h, po in mice). Cyclic sulfate 2, like topiramate and phenytoin, did not interfere with seizures induced by pentylenetetrazole, bicucculine, picrotoxin, and strychnine; also, 2 was not active in diverse in vitro receptor binding and uptake assays. However, 2 turned out to be a potent inhibitor of carbonic anhydrase from different rat tissue sources (e. g., IC50 of 84 nM for the blood enzyme and 21 nM for the brain enzyme). An examination of several analogues of 2 (83a-r, 85-87, 90a, 91a, 93a) indicated that potent anticonvulsant activity is associated with relatively small alkyl substituents on nitrogen (Me/H, 83a; Me/Me, 83m; Et/H, 83b; allyl/H, 83e; c-Pr/H, 83j; c-Bu/H, 83k) and with limited changes in the cyclic sulfate group, such as 4,5-cyclic sulfite 87a/b. The potent anticonvulsants 83a and 83j had greatly diminished carbonic anhydrase inhibitory activity; thus, inhibition of this enzyme may not be a significant factor in the anticonvulsant activity. The alpha-L-sorbopyranoses 67, 68, and 80, which mainly possess a skew conformation (ref 29), were nearly twice as potent as topiramate (1). The L-fructose enantiomers of 1 (106) and 2 (107), synthesized from L-sorbose, were found to have moderate anticonvulsant activity, with eudysmic ratios (MES ED50 in mice at 4 h, po) of 1:106 = 1.5 and 2:107 = 3.5. The log P values for 1 and 2 were determined experimentally to be 0.53 and 0.42, respectively, which are less than the optimal 2.0 for CNS active agents. However, analogues with more favorable calculated log P (clogP) values, in conjunction with just minor steric perturbation according to the developed SAR profile, such as 47 (clogP = 2.09), 83m (1.93), and 86 (1.50), did not display improved potency: 47 is less potent than 1, 83m is equipotent with 2, and 86 is less potent than 2. Although the measured log P value for diethyl analogue 31 is 1.52, this did not translate into enhanced potency relative to 1. (ABSTRACT TRUNCATED)


Many agonists induce "quantal" Ca2+ release or adaptive behavior in muscle ryanodine receptors.
Ryanodine receptors have recently been shown to undergo an unusual kind of inactivation process termed adaptation, which bears similarities to the transient calcium releases induced in other systems by successive incremental additions of inositol-1,4,5-trisphosphate. Such releases are sometimes termed "quantal". In this study we report that many agonists induce similar behavior in muscle sarcoplasmic reticulum and that the responses depend not on the calcium pumps therein but rather on the ryanodine receptors. The chemical diversity of these agonists makes it very unlikely that adaptation simply affects the sensitivity of the receptor to agonists at any one binding site. More likely, this result indicates that adaptive behavior of ryanodine receptors results whenever the ryanodine receptor is activated and that this process affects the action of most, if not all, agonists. Evidence is presented suggesting that the releases observed do not represent all-or-none releases from vesicle subpopulations (true quantal behavior) but rather seem to involve partial release from more homogeneously sensitive stores, a process referred to here as adaptation or increment detection.


Improvement in jaw motion following treatment of unilateral crossbite in a child with primary dentition: a case report.
This case report examines jaw motion during both habitual opening-closing and gum chewing in a young (3 years, 10 months) patient with unilateral crossbite at the primary dentition stage. Jaw motion was measured three times: 1. before treatment; 2. after active treatment; and 3. after retention. The abnormal habitual open-close pathway seen prior to treatment was improved after retention. Prior to treatment, movement of the affected-side condyle preceded movement of the non-affected-side condyle during opening. After retention, the movement of the condyles was better coordinated. The chopping type chewing pattern, with less lateral movement, before treatment changed to a more grinding type pattern on the affected side after activation. This study suggests that the prescribed treatment effectively improved both the patient's morphology and function. However, neither the open-close pathways nor the chewing patterns were completely normal after retention. The results in this case suggest that early treatment of functional unilateral crossbite can be effective.


Changes in Expression of Multiple Checkpoint Molecules and Infiltration of Tumor Immune Cells after Neoadjuvant Chemotherapy in Gastric Cancer.
It remains unclear that how tumor immune micro-environment will change following neoadjuvant chemotherapy (NACT) in locally advanced gastric cancer (LAGC). In this study, we aimed to characterize the changes in tumor-infiltrating immune cells and checkpoint molecules following NACT and investigate the prognostic value of these changes in LAGC. Paired tumor samples (pre-NACT and post-NACT) of 60 patients were retrospectively identified and analyzed by multiplex immunohistochemistry with a panel including CD4, CD8, FOXP3, PD-1, PD-L1, and TIM3. Following NACT, the overall median expression levels of CD4, CD8, PD1, PD-L1 and TIM3 were significantly increased (P = 0.008 for PD-L1 and P < 0.001 for all the other markers), while the median FOXP3 expression level remained stable (P = 0.120). Individually, the majority of patients presented increased expression of the markers, while 8.5%, 11.9%, 16.9%, 25.4%, 22.0% and 42.2% of patients had decreased expression of CD4, CD8, PD-1, PD-L1, TIM3 and FOXP3, respectively. Changes in expression between baseline and post-NACT of TIM3, PD-1, and PD-L1 showed strongly positive pairwise correlations with each other (P < 0.001). Multivariate analysis demonstrated that high upregulation levels of CD8 (HR = 0.73, P = 0.028), PD-1 (HR = 0.76, P = 0.027), and PD-L1 (HR = 0.67, P = 0.038) following NACT were beneficial prognostic factors of OS. NACT increase the expression of multiple checkpoint molecules and infiltration of CD4+, CD8+ immune cells in LAGC with the levels of changes in checkpoint molecules positively related with each other. This may raise the possibility of applying immunotherapy with chemotherapy or even dual checkpoint inhibitors in LAGC.


Is [F-18]-fluorodeoxyglucose FDG-PET/CT better than ct alone for the preoperative lymph node staging of muscle invasive bladder cancer?
To evaluate whether the use of [F-18]-FDG-PET/CT can accurately predict pelvic lymph node metastasis in patients with muscle invasive TCC of the bladder undergoing radical cystectomy. Fifteen patients with muscle invasive bladder cancer had undergone FDG-PET/CT scan from the skull base to the mid-thighs after IV injection of 6.5MBq (Mega-Becquerel)/Kg of FDG. After intravenous hydration IV furosemide was given to overcome the difficulties posed by urinary excretion of 18F-FDG. PET/ CT data were analyzed as PET and CT images studied separately as well as fused PET/ CT images. The imaging findings were correlated with the histopathology of the nodes (gold standard). CT and FDG-PET had demonstrated positive lymph nodes in 9 & 8 patients respectively. Among the 15 patients 3 had documented metastasis on histopathology. Both CT and PET could detect the nodes in all these 3 patients (100% sensitivity). Nodes were histologically negative amongst 6&5 patients who had node involvement by CT and PET respectively. Therefore, specificity, positive predictive value (PPV) & negative predictive value (NPV) for CT and PET/CT were 50%, 33.3%, 100% and 58.3%, 37.5%, 100% respectively. The theoretical advantage of this cutting edge technology for whole body imaging has not been translated into clinical practice as we found minimal advantage of combined FDG-PET/CT over CT alone for nodal staging of muscle invasive bladder cancer. This may be due to substantial overlap between standardized uptake values (SUVs) from active inflammatory processes with those of malignant lesion.


Prescribing clinicians' perspectives on evidence-based psychotherapy for posttraumatic stress disorder.
Evidence-based psychotherapies (EBP) for Posttraumatic Stress Disorder are not utilized to their full extent within the Department of Veterans Affairs (VA). VA provides care to many persons with PTSD and has been in the forefront of clinical practice guidelines and EBP training and dissemination. Yet VA continues to find EBP implementation difficult. Veterans with PTSD often initially present to prescribing clinicians, who then help make care decisions. It is therefore critical that these clinicians correctly screen and triage appropriate mental health care. The purpose of this study was to assess VA prescribing clinicians' knowledge, perceptions, and referral behaviors related to EBPs for PTSD and to identify facilitators and barriers to implementing EBPs within VA. We conducted qualitative interviews with 26 VA prescribing clinicians. Limited access to EBPs was the most commonly noted barrier. The clinicians we interviewed also held specific beliefs and behaviors that may delay or deter EBPs. Strategies to improve utilization also emerged. Findings suggest the need for increased access to EBPs, training to optimize the role of prescribing clinicians in helping Veterans with PTSD make appropriate care decisions, and specific organizational changes to facilitate access and effective referral systems for EBPs.


The influence of delirium on mortality and length of ICU stay and analysis of risk factors for delirium after liver transplantation.
To analyze the incidence, timing, risk factors and prognosis of delirium after liver transplantation (LT). The clinical data of 321 patients undergoing LT in the Third Xiangya Hospital of Central South University from January 2018 to December 2022 were collected to investigate the incidence, onset, and risk factors for post-LT delirium and the impact of delirium on LT recipients' prognosis by statistical analysis. The incidence of post-LT delirium was 19.3% (62/321), and the median interval between LT and onset of delirium was 20.1 h. Univariate analysis showed that pre-LT variables (Model for End Stage Liver Disease (MELD) score, hospital stay, hepatic encephalopathy, infection, white blood cell (WBC) count, lymphocyte count, abnormal potassium, lactulose use), intraoperative variables (red blood cell transfusion, remimazolam use, dexmedetomidine use) and post-LT variables (hypernatraemia, acute rejection, reoperation, basiliximab use, tacrolimus concentration) were associated with post-LT delirium. Multivariate logistic regression analysis revealed that MELD score at LT ≥22 [OR = 3.400, 95% CI:1.468-7.876, p = 0.004], pre-LT hepatic encephalopathy [OR = 3.224, 95% CI:1.664-6.244, p = 0.001], infection within 2 months prior to LT [OR = 2.238, 95% CI:1.151-4.351, p = 0.018], acute rejection [OR = 2.974, 95% CI:1.322-6.690, p = 0.008], and reoperation [OR = 11.919, 95% CI:2.938-48.350, p = 0.001] were independent risk factors for post-LT delirium. Post-LT delirium was reduced in LT recipients exposing to intraoperative remimazolam [OR = 0.287, 95% CI: 0.113-0.733, p = 0.009] or ≥ 25 μg of intraoperative dexmedetomidine [OR = 0.441, 95% CI 0.225-0.867, p = 0.018]. As for clinical outcomes, patients with delirium had a higher percentage of staying at the (ICU) ≥7 d after LT than those without delirium [OR = 2.559, 95% CI 1.418-4.617, p = 0.002]. The incidence of delirium was high and the onset of delirium was early after LT. Risk factors for post-LT delirium included high MELD score at LT, pre-LT hepatic encephalopathy and infections, acute rejection and reoperation. Intraoperative use of remimazolam or dexmedetomidine reduced post-LT delirium. Delirium had a negative impact on the length of ICU stay.


Electron attachment to gas-phase uracil.
We present results about dissociative electron attachment (DEA) to gas-phase uracil (U) for incident electron energies between 0 and 14 eV using a crossed electron/molecule beam apparatus. The most abundant negative ion formed via DEA is (U-H)-, where the resonance with the highest intensity appears at 1.01 eV. The anion yield of (U-H)- shows a number of peaks, which can be explained in part as being due to the formation of different (U-H)- isomers. Our results are compared with high level ab initio calculations using the G2MP2 method. There was no measurable amount of a parent ion U-. We also report the occurrence of 12 other fragments produced by dissociative electron attachment to uracil but with lower cross sections than (U-H)-. In addition we observed a parasitic contaminating process for conditions where uracil was introduced simultaneously with calibrant gases SF6 and CCl4 that leads to a sharp peak in the (U-H)- cross section close to 0 eV. For (U-H)- and all other fragments we determined rough measures for the absolute partial cross section yielding in the case of (U-H)- a peak value of sigma (at 1.01 eV)=3 x 10(-20) m2.