Low-grade gliomas in older patients: long-term follow-up from Mayo Clinic.
Low-grade gliomas (LGGs) are uncommon in older patients, and long-term clinical behavior and prognostic factors are not well defined in this group. The authors retrospectively searched their tumor registry for the records of adult patients (> or =18 years) diagnosed as having nonpilocytic LGG between 1960 and 1992 at Mayo Clinic. The Kaplan-Meier method was used to estimate progression-free survival and overall survival (OS) in patients aged 55 years and older. Of 314 patients initially identified, 32 were aged at least 55 years, with a median age at diagnosis of 61 years (range, 55-74 years). Median follow-up was 17.3 years for survivors. Operative pathologic diagnoses comprised astrocytoma (n = 22, 69%), mixed oligoastrocytoma (n = 7, 22%), and oligodendroglioma (n = 3, 9%). Gross total resection was achieved in 1 patient, radical subtotal resection in 1, and subtotal resection in 14; 16 patients had biopsy only. Postoperative radiotherapy or chemotherapy was given to 23 (72%) patients and 1 (3%) patient, respectively. Median OS was 2.7 years for all patients: 3 years with resection and 2.2 years with biopsy only (P = .58). The 5- and 10-year OS rates were 31% and 18%, respectively. Factors adversely affecting OS on univariate analysis were enhancement on computed tomography (P < .001) and supratentorial location (P = .03). This retrospective series of older patients suggests that intracranial LGG in this age group behaves aggressively. Pathologic sampling error failing to recognize higher-grade tumors does not seem to account for these poor outcomes. Aggressive management with maximally safe resection followed by adjuvant therapy should be strongly considered.


Alignment of multiple glial cell populations in 3D nanofiber scaffolds: toward the development of multicellular implantable scaffolds for repair of neural injury.
Non-neuronal cells of the central nervous system (CNS), termed "neuroglia," play critical roles in neural regeneration; therefore, replacement of glial populations via implantable nanofabricated devices (providing a growth-permissive niche) is a promising strategy to enhance repair. Most constructs developed to date have lacked three-dimensionality, multiple glial populations and control over spatial orientations, limiting their ability to mimic in vivo neurocytoarchitecture. We describe a facile technique to incorporate multiple glial cell populations [astrocytes, oligodendrocyte precursor cells (OPCs) and oligodendrocytes] within a three-dimensional (3D) nanofabricated construct. Highly aligned nanofibers could induce elongation of astrocytes, while OPC survival, elongation and maturation required pre-aligned astrocytes. The potential to scale-up the numbers of constituent nanofiber layers is demonstrated with astrocytes. Such complex implantable constructs with multiple glial sub-populations in defined 3D orientations could represent an effective approach to reconstruct glial circuitry in neural injury sites. Clinically available methods to enhance nervous tissue regeneration remain scarce despite decades of research. In this study, a novel 3D nanofabricated construct is demonstrated, that includes populations of astrocytes, oligodendrocyte precursor cells and oligodendrocytes providing a well-orchestrated glial microenvironment for more efficient central nervous system repair.


[Study on the preparation of TK-gene nanoparticles and its expression].
To prepare TK-gene nanoparticles and investigate its expression. Biodegradable and biocompatible polymer polylactic-co-glycolic acid (PLGA) was used to prepare recombinant plasmid pEGFP-AFP nanoparticles by double-emulsion evaporation technique. The characteristics of the nanopticicles including morphology, entrapment efficiency was investigated. The expression of TK gene was also investigated by MTT assay, which could determine the dying cells after the addition of gancyclovir (GCV). The enhanced green fluorescent protein (EGFP) expression in human hepatocarcinoma SMMC-7221 cells and human normal parenchymal Chang liver cells were assessed by flow cytometric analysis. The resulting plasmid-nanoparticles had regular spherical surface and a narrow particle size with a mean diameter of (72 +/- 12) nm, The average entrapment efficiency was 91.25%, the enhanced transfection efficiency and ability protecting plasmid DNA from degraded by nuclease or sonication due to nanoparticles encapsulation. DNA-nanoparticles need further study as gene delivery system.


The experience of sleep in chronic fatigue syndrome: A qualitative interview study with patients.
Sleep disturbances are common in chronic fatigue syndrome (CFS), and one of the key symptom complaints, yet it has been neglected by previous qualitative research. The aim was to explore the specific role of sleep in patients' experience of their illness. A qualitative semi-structured interview format facilitated a detailed and open exploration of sleep, and the extent to which its management and problems were linked to the lived experience of CFS. Eleven semi-structured interviews were conducted with individuals with CFS. Data were transcribed verbatim and analysed thematically, to explore and describe patients' experience of their sleep, and its impact on their condition. Sleep emerged as a key aspect of the illness experience, and its management and effect on daytime functioning was a central pre-occupation for all 11 participants; all of them saw sleep as playing a critical role in their illness through either maintaining or exacerbating existing symptoms. Exploration of individual experiences presented three overarching themes: (1) sleep pattern variability over illness course and from day to day; (2) effect of sleep on daytime functioning; and (3) attempts at coping and sleep management. Each patient with CFS has a unique experience of sleep. Despite the differing narratives regarding the role of sleep in CFS, all participants held the belief that sleep is a vital process for health and well-being which has had a direct bearing on the course and progression of their CFS. Also, every participant regarded their sleep as in some way 'broken' and in need of management/repair. Patients' insights demonstrate sleep-specific influences on their CFS, and the impact of disturbed sleep should be a consideration for clinical and research work. What is already known on this subject? Sleep disturbances are common in CFS, and one of the key symptom complaints, yet it has been neglected by previous qualitative research. Ontology of CFS is a matter of dispute, with models ranging from the biological to the psychological competing to explain symptomatology in this illness. A qualitative study has the potential to add some clarity to the debate by making the patients' lived experience of the condition, and their own understanding of it, the focus of research. What this study adds? Coping and attempts at managing sleep problems in CFS adds to the 'illness burden' experienced by patients. Disturbed sleep is universally seen by patients with CFS as impacting on other daytime symptoms. Broken sleep may contribute to a biopsychosocial cycle that serves to maintain this illness.


Proposed changes in personality and personality disorder assessment and diagnosis for DSM-5 Part I: Description and rationale.
A major reconceptualization of personality psychopathology has been proposed for DSM-5 that identifies core impairments in personality functioning, pathological personality traits, and prominent pathological personality types. A comprehensive personality assessment consists of four components: levels of personality functioning, personality disorder types, pathological personality trait domains and facets, and general criteria for personality disorder. This four-part assessment focuses attention on identifying personality psychopathology with increasing degrees of specificity, based on a clinician's available time, information, and expertise. In Part I of this two-part article, we describe the components of the new model and present brief theoretical and empirical rationales for each. In Part II, we will illustrate the clinical application of the model with vignettes of patients with varying degrees of personality psychopathology, to show how assessments might be conducted and diagnoses reached.


Sustainable wheat (Triticum aestivum L.) production in saline fields: a review.
A large part of global agricultural fields, including the wheat (Triticum aestivum L.) ones, are subjected to various stresses including salinity. Given the increasing world population, finding methods and strategies that can alleviate salinity stress on crop yield production is of outmost importance. The presented review has consulted more than 400 articles related to the clean and sustainable production of wheat in saline fields affected by biological, environmental, economical, and social parameters including the important issue of climate change (global warming). The negative effects of salt stress on plant growth and the techniques, which have been so far detected to alleviate salinity stress on wheat growth have been analyzed and presented. The naturally tolerant species of wheat can use a range of mechanisms to alleviate salinity stress including sodium exclusion, potassium retention, and osmoregulation. However, the following can be considered as the most important techniques to enhance wheat tolerance under stress: (1) the biotechnological (crop breeding), biological (soil microbes), and biochemical (seed priming) methods, (2) the use of naturally tolerant genotypes, and (3) their combined use. The proper handling of irrigation water is also an important subject, which must be considered when planting wheat in saline fields. In conclusion, the sustainable and cleaner production of wheat under salt stress is determined by a combination of different parameters including the biotechnological techniques, which if handled properly, can enhance wheat production in saline fields.


Base-controlled chemoselectivity reaction of vinylanilines with isothiocyanates for synthesis of quinolino-2-thione and 2-aminoquinoline derivatives.
Here, we report a base-controlled chemo-selective reaction of vinylanilines with alkyl/aryl isothiocyanates to afford quinolino-2-thione and 2-aminoquinoline derivatives. The quinolino-2-thiones could be obtained in high yields in the presence of Et3N. Particularly interesting is that the reaction could produce the 2-aminoquinolines in the presence of K3PO4 with high selectivity.


The macroeconomics of abortion: A scoping review and analysis of the costs and outcomes.
Although abortion is a common gynecological procedure around the globe, we lack synthesis of the known macroeconomic costs and outcomes of abortion care and abortion policies. This scoping review synthesizes the literature on the impact of abortion-related care and abortion policies on economic outcomes at the macroeconomic level (that is, for societies and nation states). Searches were conducted in eight electronic databases. We conducted the searches and application of inclusion/exclusion criteria using the PRISMA extension for Scoping Reviews. For inclusion, studies must have examined one of the following macroeconomic outcomes: costs, impacts, benefits, and/or value of abortion care or abortion policies. Quantitative and qualitative data were extracted for descriptive statistics and thematic analysis. Of the 189 data extractions with macroeconomic evidence, costs at the national level are the most frequently reported economic outcome (n = 97), followed by impacts (n = 66), and benefits/value (n = 26). Findings show that post-abortion care services can constitute a substantial portion of national expenditures on health. Public sector coverage of abortion costs is sparse, and individuals bear most of the costs. Evidence also indicates that liberalizing abortion laws can have positive spillover effects for women's educational attainment and labor supply, and that access to abortion services contributes to improvements in children's human capital. However, the political economy around abortion legislation remains complicated and controversial. Given the highly charged political nature of abortion around the global and the preponderance of rhetoric that can cloud reality in policy dialogues, it is imperative that social science researchers build the evidence base on the macroeconomic outcomes of abortion services and regulations.


Technique for measuring photometric accuracy.
A convenient photometric linearity test that meets stringent criteria for accuracy and practicality is described. Experience with alternate, commonly advocated methods illustrates the need for an improved approach. The method described herein relies on direct application of physical principles. It combines use of Bouguer's law and superposition of optical fields. Each technique overcomes a deficiency in the other. Peak errors in absorbance were found to be 0.0011 or less in a commercial spectrophotometer equipped with a specially calibrated potentiometer and were primarily attributable to phototubes.


Congenital mirror movements are associated with defective polymerisation of RAD51.
Mirror movements are involuntary movements of one hand that mirror intentional movements of the other hand. Congenital mirror movements (CMM) is a rare genetic disorder with autosomal dominant inheritance, in which mirror movements are the main neurological manifestation. CMM is associated with an abnormal decussation of the corticospinal tract, a major motor tract for voluntary movements. RAD51 is known to play a key role in homologous recombination with a critical function in DNA repair. While RAD51 haploinsufficiency was first proposed to explain CMM, other mechanisms could be involved. We performed Sanger sequencing of RAD51 in five newly identified CMM families to identify new pathogenic variants. We further investigated the expression of wild-type and mutant RAD51 in the patients' lymphoblasts at mRNA and protein levels. We then characterised the functions of RAD51 altered by non-truncating variants using biochemical approaches. The level of wild-type RAD51 protein was lower in the cells of all patients with CMM compared with their non-carrier relatives. The reduction was less pronounced in asymptomatic carriers. In vitro, mutant RAD51 proteins showed loss-of-function for polymerisation, DNA binding and strand exchange activity. Our study demonstrates that RAD51 haploinsufficiency, including loss-of-function of non-truncating variants, results in CMM. The incomplete penetrance likely results from post-transcriptional compensation. Changes in RAD51 levels and/or polymerisation properties could influence guidance of the corticospinal axons during development. Our findings open up new perspectives to understand the role of RAD51 in neurodevelopment.


T2* mapping with background gradient correction using different excitation pulse shapes.
Background gradients induced by magnetic susceptibility variations near air-filled cavities in the brain cause signal-intensity loss in gradient-echo images and shorten T2* considerably. With a correction method in which the exponential decay is restored with section-profile-dependent correction factors, parts of the signal intensity can be recovered. While uncorrected T2* values drop by 20% at a gradient strength of 75 μT/m, with correction and exponential excitation pulses, this boundary is pushed to 220 μT/m.


Plasticity in the Link between Pain-Transmitting and Pain-Modulating Systems in Acute and Persistent Inflammation.
There is strong evidence that spinoparabrachial neurons in the superficial dorsal horn contribute to persistent pain states, and that the lateral parabrachial complex (PB) conveys relevant nociceptive information to higher structures. The role of PB itself in hyperalgesia and how it recruits descending facilitation has nevertheless received significantly less attention. The current study is a first step toward delineating the functional dynamics of PB and its link to descending control in acute and persistent inflammatory pain. In lightly anesthetized rats, we recorded behavioral withdrawal evoked by mechanical stimulation of the hindpaw and, simultaneously, the activity of identified pain-modulating neurons, "ON-cells" and "OFF-cells," in the rostral ventromedial medulla (RVM). This was done before and after the inactivation of PB, contralateral or ipsilateral to an inflamed paw [1 h, 1 d, or 5-6 d after intraplantar injection of Complete Freund's Adjuvant (CFA)]. The inactivation of contralateral, but not ipsilateral, PB interfered with nociceptive input to RVM under basal conditions, as well as in acute inflammation. By contrast, blocking ipsilateral, but not contralateral, PB in established inflammation interfered with behavioral hyperalgesia and ON-cell and OFF-cell responses. The lesioning of contralateral PB before CFA injection prevented this recruitment of ipsilateral PB in persistent inflammation. These experiments show that contralateral PB is required to initiate hyperalgesia, which is then maintained by ipsilateral PB, most likely in both cases via the engagement of pain-modulating neurons of the RVM.SIGNIFICANCE STATEMENT The lateral parabrachial complex (PB) relays nociceptive information to brain circuits that are important for the transmission and modulation of pain, but its specific role in persistent pain and engagement of descending control mechanisms has received relatively little attention. We show here that PB contralateral and ipsilateral to an inflammatory insult demonstrate different functions as inflammation persists, likely by engaging pain-facilitating neurons of the rostral ventromedial medulla. While the contralateral PB, the target of the major spinoparabrachial pathway, relays acute nociceptive information, the ipsilateral PB is recruited or unmasked in persistent inflammation to maintain hyperalgesia. These data point to plasticity in the PB itself or its direct and indirect connections with pain-modulating systems as central to the development and maintenance of persistent pain.


Genetic control of uterine receptivity during implantation.
Implantation involves complex molecular interactions between implanting blastocysts and the hormonally primed uterus. Gene targeting allows the generation of mice lacking a specific gene or genes and has proved to be of considerable value when combined with classical physiology in understanding many biological questions, such as the process of implantation. In this article, we review genes that have been demonstrated by gene targeting in mice to be required in the uterus for implantation. In particular, we focus on a specific class of developmental control genes, the mammalian Hox genes, and their role in this process. Lastly, we attempt to synthesize current knowledge about the genetic control of implantation and to build a working genetic model for the implantation pathway.


Renal assimilation of oligopeptides: physiological mechanisms and metabolic importance.
Assimilation of systemic oligopeptides (di- and tripeptides) is largely a function of kidneys. The most specific and unique mechanism utilized for the performance of this renal function is transport, followed by intracellular hydrolysis and then release of constituent amino acids to the systemic circulation. Among tissues examined (liver, kidney, intestine, and muscle), kidney is the only tissue capable of accumulating dipeptides in concentrations that are greater than their plasma concentrations. Kidney also is the tissue with the highest cytoplasmic dipeptidase activity. Intracellular accumulation is mediated by two transporters (Pept-1 and Pept-2), both of which have been recently cloned. These transporters use dipeptides and tripeptides as substrates and rely on protons and membrane potential for their driving force. Pept-1 is a low-affinity, high-capacity transporter, and Pept-2 is a high-affinity, low-capacity transporter. The nutritional and metabolic regulation of renal assimilation of oligopeptides is suggested by the selective decrease in dipeptide balance across the kidneys of starved human subjects and by the insulin stimulation of dipeptide transport by a renal cell line. Peptiduria has been observed in a variety of diseases, but the mechanism, except in genetic diseases affecting hydrolysis of oligopeptides, is not known. Finally, the capacity for active transport of oligopeptides and peptidomimetic drugs enables kidneys to play major roles in nutritional and pharmacological therapies.


Regulatory sequences for the amplification and replication of the ribosomal DNA minichromosome in Tetrahymena thermophila.
We have analyzed the cis-acting sequences that regulate rRNA gene (rDNA) replication in Tetrahymena thermophila. The macronucleus of this ciliated protozoan contains 9,000 copies of a 21-kbp minichromosome in the form of a palindrome comprising two copies of the rDNA. These are derived from a single chromosomally integrated copy during conjugation through selective amplification and are maintained by replicating once per cell cycle during vegetative growth. We have developed a transformation vector and carried out a deletion analysis to determine the minimal sequences required for replication, amplification, and/or stable maintenance of the rDNA molecule. Using constructs containing progressively longer deletions, we show that only a small portion (approximately 900 bp) of the rDNA is needed for extrachromosomal replication and stable maintenance of this molecule. This core region is very near but does not include the rRNA transcription initiation site or its putative promoter, indicating that replication is not dependent on normal rRNA transcription. It includes two nearly identical nuclease-sensitive domains (D1 and D2), one of which (D1) corresponds to the physical origin of replication determined previously. Deletion of both domains abolishes replication, whereas deletion of either domain allows the molecules to replicate, indicating that only one domain is required. In addition to this core region, we have found several DNA segments, including a tandem array of a 21-nucleotide repeat (type II repeats) and sequences within the rRNA coding region, that play distinctive and important roles in maintaining the rDNA at a high copy number.


Adjuvant chemotherapy and risk of gastrointestinal, hematologic, and cardiac toxicities in elderly patients with stage III colon cancer.
Randomized trials have established the effectiveness of 5-fluorouracil-based adjuvant chemotherapy for stage III resectable colon cancer but the toxicity has not been well established outside the trial setting. The objective of this study was to estimate the risk of various toxicity-related endpoints among the elderly patients. Patients diagnosed with stage III colon cancer in 1991 to 2005 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Chemotherapy use within 3 months after tumor resection was identified from submitted claims. We reported the 3-month cumulative incidence rate (CIR) for gastrointestinal and hematologic toxicities. The risk of ischemic heart disease in relation to chemotherapy use and length was assessed using Cox regression models, stratified by age and comorbidity subgroups. Of the 12,099 patients, 63.9% (n=7740) received adjuvant chemotherapy. Common gastrointestinal and hematologic toxicities among chemotherapy group include volume depletion disorder (CIR=9.1%), agranulocytosis (CIR=3.4%), diarrhea (CIR=2.4%), nausea and vomiting (CIR=2.3%). Chemotherapy use was significantly associated with the onset of these toxicities [hazard ratio (HR)=2.76; 95% confidence interval (95% CI)=2.42-3.15]. The risk of ischemic heart disease was slightly associated with chemotherapy use (HR=1.08, 95% CI=0.96-1.22), but significant only among patients aged <75 years with a comorbidity score equal to 0 (HR=1.70; 95% CI=1.02-2.84). Chemotherapy was associated with the increased risk of developing gastrointestinal, hematologic, and cardiac toxicities in patients with colon cancer. On account of the effects of these side effects on treatment discontinuation, rehospitalization, and overall health status, some close monitoring and preventive measures may be emphasized to maximize the benefits of adjuvant chemotherapy.


Factors influencing survival among patients with HER2-positive metastatic breast cancer treated with trastuzumab.
We have limited capability to predict survival among patients treated for metastatic HER2-positive breast cancer. Further research is warranted to identify significant prognostic and predictive factors. We identified all HER2-positive metastatic breast cancer patients receiving trastuzumab at the Sunnybrook Odette Cancer Centre (SOCC) from 1999 to 2013 through the Cancer Care Ontario (CCO) Registry (n = 256) and selected patients with available pathology reports (n = 154). A retrospective review was completed documenting clinical, pathologic, and laboratory characteristics at the time of first trastuzumab therapy and survival outcomes. Cox proportional hazards regression models were used to identify prognostic factors for overall survival (OS) (primary endpoint) and failure-free survival (FFS), adjusted for the known prognostic factors of the presence of CNS metastases and the presence of ≥ 2 distant metastatic sites. A multivariable model identified older age [hazard ratio (HR) 1.18/decade, 95% confidence interval (CI) 1.02-1.37)], increased platelet-to-lymphocyte ratio (PLR) (HR 1.75/log-unit, 95% CI 1.25-2.46), increased serum alkaline phosphatase (ALP) (HR 1.87/log-unit, 95% CI 1.41-2.49), and ER positivity (HR 0.63, 95% CI 0.42-0.96) as significant prognostic factors for OS after adjusting for the presence of CNS metastasis (HR 3.19, 95% CI 1.59-6.38) and the presence of ≥ 2 distant metastatic sites (HR 2.10, 95% CI 1.19-3.70). PLR (HR 1.54/log-unit, 95% CI 1.12-2.12) was the only prognostic factor associated with FFS after adjusting for CNS and ≥ 2 distant metastatic sites. Older age, increased PLR, and ALP were identified as poor prognostic factors and ER positivity as a favorable prognostic factor for OS after adjusting for the presence of CNS metastasis and the presence of number of ≥ 2 distant metastatic sites. Increased PLR was a poor prognostic factor for both OS and FFS, and warrants further investigation into its prognostic ability amongst patients with HER2-positive metastatic breast cancer.


Familial hypercholesterolemia in St-Petersburg: the known and novel mutations found in the low density lipoprotein receptor gene in Russia.
Familial hypercholesterolemia is a human monogenic disease caused by population-specific mutations in the low density lipoprotein (LDL) receptor gene. Despite thirteen different mutations of the LDL receptor gene were reported from Russia prior to 2003, the whole spectrum of disease-causing gene alterations in this country is poorly known and requires further investigation provided by the current study. Forty-five patients with clinical diagnosis of FH were tested for the apolipoprotein B (apoB) mutation R3500Q by restriction fragment length analysis. After exclusion of R3500Q mutation high-sensitive fluorescent single-strand conformation polymorphism (SSCP) analysis and automatic DNA sequencing were used to search for mutations in the LDL receptor gene. We found twenty one rare sequence variations of the LDL receptor gene. Nineteen were probably pathogenic mutations, and two (P518P, T705I) were considered as neutral ones. Among the mutations likely to be pathogenic, eight were novel (c.670-671insG, C249X, c.936-940del5, c.1291-1331del41, W422X, c.1855-1856insA, D601N, C646S), and eleven (Q12X, IVS3+1G>A, c.651-653del3, E207X, c.925-931del7, C308Y, L380H, c.1302delG, IVS9+1G>A, V776M, V806I) have already been described in other populations. None of the patients had the R3500Q mutation in the apoB gene. Nineteen pathogenic mutations in the LDL receptor gene in 23 probands were identified. Two mutations c.925-931del7 and L380H are shared by St.-Petersburg population with neighbouring Finland and several other mutations with Norway, Sweden or Denmark, i.e. countries from the Baltic Sea region. Only four mutations (c.313+1G>A, c.651-653del3, C308Y and W422X) were recurrent as all those were found in two unrelated families. By this study the number of known mutations in the LDL receptor gene in St.-Petersburg area was increased nearly threefold. Analysis of all 34 low density lipoprotein receptor gene mutations found in St.-Petersburg argues against strong founder effect in Russian familial hypercholesterolemia.


Amoebic liver abscess in the medical emergency of a North Indian hospital.
Amoebic Liver abscess although fairly common in developing countries, yet, there is limited data on the clinical presentation to the emergency department. A retrospective analysis of 86 indoor cases of Amoebic Liver Abscess presenting to the emergency department over a 5-year period was carried out. The mean age of patients was 40.5 +/- 2.1 years (male-female ratio = 7:1). Fever, pain abdomen and diarrhea were seen in 94%, 90% and 10.5% respectively. Duration of symptoms less than 2 weeks was seen in 48% cases. Hepatomegaly was present in 16% cases only, a right sided pleural effusion in 14% cases and ascites in 5.7%. On ultrasound, a right lobe abscess was seen in 65%, a left lobe abscess in 13% and multiple abscesses in both the lobes in 22% cases. Seventy one cases underwent per-cutaneous pigtail catheter drainage for a mean period of 13.4 +/- 0.8 days. The mortality rate was 5.8%. On multivariate regression and correlation analysis, a higher number of inserted pigtail catheters correlated to mortality. Amoebic liver abscess presents commonly to the emergency department and should be suspected in persons with prolonged fever and pain abdomen. Conservative management for uncomplicated amoebic liver abscess and insertion of single per-cutaneous pigtail catheter drainage for complicated amoebic liver abscess are efficacious as treatment modalities.


Impact of first eye cataract surgery on falls among patients of advanced age: a comparative study.
To compare the incidence of falls between patients with visually significant cataracts in both eyes and those who have undergone first-eye cataract surgery. This retrospective case-control study involved patients with a history of cataracts in both eyes who had undergone first-eye cataract surgery within the past 9 to 12 months (pseudophakic group). The control group comprised patients with cataracts in both eyes (cataract group). We assessed best-corrected visual acuity (BCVA), systemic comorbidities and medications (using the Charlson comorbidity index), and independent daily activities (using the Lawton Instrumental Activities of Daily Living scale). The patients were questioned about experiencing two or more falls in the last 6 months. Each group comprised 50 patients. Binocular BCVA was significantly better in the pseudophakic group (0.05 ± 0.06 logMAR) than in the cataract group (0.77 ± 0.34 logMAR). Of all participants, 22% reported experiencing two or more falls in the last 6 months. Multivariate analysis demonstrated significantly better BCVA in participants with less than two falls. Patients of advanced age with visually significant cataracts in both eyes are at a higher risk of falling. First-eye cataract surgery may mitigate the occurrence of falls by improving binocular BCVA.


Annual risk of tuberculous infection in the northern zone of India.
To estimate the annual risk of infection with tubercle bacilli in the northern zone of India. A community-based cross-sectional tuberculin survey was conducted among children aged 1-9 years who lived in a sample of villages and urban blocks of six selected districts in a defined north zone of India. A two-stage cluster sampling method was used to select rural and urban clusters. A total of 48 624 children in 598 clusters were subjected to tuberculin testing with one tuberculin unit (1 TU) of PPD RT23 stabilized with Tween 80. The maximum transverse diameter of induration was measured about 72 hours after the test. Among the 48 624 test-read children, 22 064 (45.4%) had a bacille Calmette-Gu rin (BCG) scar. On the basis of the frequency distribution of tuberculin reaction size among 25 816 children without a BCG scar, the prevalence of infection with tubercle bacilli was estimated as 10.3%. The annual risk of infection was computed as 1.9%. The proportion of infected children was significantly higher in urban than rural areas. The high rate of tuberculous infection in the north zone of India suggests the need for further intensification of tuberculosis control efforts on a sustained and long-term basis.


Hydrolysis of third-generation cephalosporins by class C beta-lactamases. Structures of a transition state analog of cefotoxamine in wild-type and extended spectrum enzymes.
Bacterial resistance to the third-generation cephalosporins is an issue of great concern in current antibiotic therapeutics. An important source of this resistance is from production of extended-spectrum (ES) beta-lactamases by bacteria. The Enterobacter cloacae GC1 enzyme is an example of a class C ES beta-lactamase. Unlike wild-type (WT) forms, such as the E. cloacae P99 and Citrobacter freundii enzymes, the ES GC1 beta-lactamase is able to rapidly hydrolyze third-generation cephalosporins such as cefotaxime and ceftazidime. To understand the basis for this ES activity, m-nitrophenyl 2-(2-aminothiazol-4-yl)-2-[(Z)-methoxyimino]acetylaminomethyl phosphonate has been synthesized and characterized. This phosphonate was designed to generate a transition state analog for turnover of cefotaxime. The crystal structures of complexes of the phosphonate with both ES GC1 and WT C. freundii GN346 beta-lactamases have been determined to high resolution (1.4-1.5 Angstroms). The serine-bound analog of the tetrahedral transition state for deacylation exhibits a very different binding geometry in each enzyme. In the WT beta-lactamase the cefotaxime-like side chain is crowded against the Omega loop and must protrude from the binding site with its methyloxime branch exposed. In the ES enzyme, a mutated Omega loop adopts an alternate conformation allowing the side chain to be much more buried. During the binding and turnover of the cefotaxime substrate by this ES enzyme, it is proposed that ligand-protein contacts and intra-ligand contacts are considerably relieved relative to WT, facilitating positioning and activation of the hydrolytic water molecule. The ES beta-lactamase is thus able to efficiently inactivate third-generation cephalosporins.


Long non-coding RNA ANRIL promotes tumorgenesis through regulation of FGFR1 expression by sponging miR-125a-3p in head and neck squamous cell carcinoma.
ANRIL (CDKN2B antisense RNA 1, CDKN2B-AS1) is involved in the progression of various cancers. However, its role in head and neck squamous cell carcinoma (HNSCC) remains unclear. In this study, we found that ANRIL expression was upregulated in HNSCC and correlated with tumor progression. Further functional analysis showed that knockdown of ANRIL significantly inhibited proliferation in vivo and in vitro. ANRIL functioned as a ceRNA (competing endogenous RNAs) for miR-125a-3p and upregulated FGFR1 (fibroblast growth factor receptor-1), which could promote tumor growth. Moreover, we confirmed that ANRIL promoted HNSCC activity via FGFR1 with a FGFR1 inhibitor in vivo and in vitro. Thus, it could be concluded that ANRIL promoted the progression of HNSCC via miR-125a-3p/FGFR1/MAPK signaling, which might provide a new target for the diagnosis and treatment of HNSCC.


Recent advancements in exon-skipping therapies using antisense oligonucleotides and genome editing for the treatment of various muscular dystrophies.
Muscular dystrophy is a group of genetic disorders characterised by degeneration of muscles. Different forms of muscular dystrophy can show varying phenotypes with a wide range of age, severity and location of muscle deterioration. Many palliative care options are available for muscular dystrophy patients, but no curative treatment is available. Exon-skipping therapy aims to induce skipping of exons with disease-causing mutations and/or nearby exons to restore the reading frame, which results in an internally truncated, partially functional protein. In antisense-mediated exon-skipping synthetic antisense oligonucleotide binds to pre-mRNA to induce exon skipping. Recent advances in exon skipping have yielded promising results; the US Food and Drug Administration (FDA) approved eteplirsen (Exondys51) as the first exon-skipping drug for the treatment of Duchenne muscular dystrophy, and in vivo exon skipping has been demonstrated in animal models of dysferlinopathy, limb-girdle muscular dystrophy type 2C and congenital muscular dystrophy type 1A. Novel methods that induce exon skipping utilizing Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are also being developed where splice site mutations are created within the genome to induce exon skipping. Challenges remain as exon-skipping agents can have deleterious non-specific effects and different in-frame deletions show phenotypic variance. This article reviews the state of the art of exon skipping for treating muscular dystrophy and discusses challenges and future prospects.


Use of colistin in a pediatric burn unit in Argentina.
The use of sulfomethate sodium colistin for the treatment of infections caused by multiple drug resistant (MDR) Gram-negative microorganisms were studied in a burn unit to evaluate the safety of this drug. A prospective chart review of pediatric patients treated with intravenous colistin in a tertiary burn unit between January 2005 and December 2006 was performed. Forty-five courses of intravenous colistin treatment administered to 45 children were evaluated in the study period. Fourteen patients (31%) were infected by Pseudomonas aeruginosa spp and 20 patients (44.5%) by Acinetobacter spp and an association of both bacteria was found in six patients (13.5%).The mean age of the patients was 52 months (range, 2 to 168 months), and 28 patients (62%) were men. The percentage of burnt body surface was between 9 and 87% (mean, 38%). Forty patients (89%) were infected by MDR organisms. Colistin was empirically indicated in five patients (11%) with burn wound sepsis 7 days after admission to the unit despite negative cultures. Burn wound sepsis was the most frequent focus of infection in 19 patients (42%). In 14 patients (31%), burn wound infection occurred without sepsis. Intravascular catheter-related bacteremia occurred in three patients (7%) and bacteremia in one (2%). Three patients had pneumonia (7%), three osteomyelitis (7%), and two urinary tract infection (4%).The length of treatment with colistin was between 3 and 92 days (median, 21 days). Only one patient (2%) died for reasons other than infection. None of the children developed increases in serum creatinine concentrations or neurological complications during treatment with colistin. Colistin seems to be a safe drug in selected cases of infections with MDR Gram-negative microorganisms. Further studies are needed to confirm these results.


Dental caries: strategies to control this preventable disease.
To provide a brief commentary review of strategies to control dental caries. Dental decay is one of man's most prevalent diseases. In many counties, severity increased in parallel with importation of sugar, reaching its zenith about 1950s and 1960s. Since then, severity has declined in many countries, due to the wide use of fluoride especially in toothpaste, but dental caries remains a disease of medical, social and economic importance. Within the EU in 2011, the cost of dental treatment was estimated to be €79 billion. The pathogenesis is well understood: bacteria in dental plaque (biofilm) metabolise dietary sugars to acids which then dissolve dental enamel and dentine. Possible approaches to control caries development, therefore, involve: removal of plaque, reducing the acidogenic potential of plaque, reduction in sugar consumption, increasing the tooth's resistance to acid attack, and coating the tooth surface to form a barrier between plaque and enamel. At the present time, only three approaches are of practical importance: sugar control, fluoride, and fissure sealing. The evidence that dietary sugars are the main cause of dental caries is extensive, and comes from six types of study. Without sugar, caries would be negligible. Fluoride acts in several ways to aid caries prevention. Ways of delivering fluoride can be classed as: 'automatic', 'home care' and 'professional care': the most important of these are discussed in detail in four articles in this issue of the Acta Medica Academica. Dental caries is preventable - individuals, communities and countries need strategies to achieve this.


Warhead Reactivity Limits the Speed of Inhibition of the Cysteine Protease Rhodesain.
Viral and parasitic pathogens rely critically on cysteine proteases for host invasion, replication, and infectivity. Their inhibition by synthetic inhibitors, such as vinyl sulfone compounds, has emerged as a promising treatment strategy. However, the individual reaction steps of protease inhibition are not fully understood. Using the trypanosomal cysteine protease rhodesain as a medically relevant target, we design photoinduced electron transfer (PET) fluorescence probes to detect kinetics of binding of reversible and irreversible vinyl sulfones directly in solution. Intriguingly, the irreversible inhibitor, apart from its unlimited residence time in the enzyme, reacts 5 times faster than the reversible one. Results show that the reactivity of the warhead, and not binding of the peptidic recognition unit, limits the rate constant of protease inhibition. The use of a reversible inhibitor decreases the risk of off-target side effects not only by allowing its release from an off-target but also by reducing the rate constant of binding.


Feasibility, safety, and compliance in a randomized controlled trial of physical therapy for Parkinson's disease.
Both efficacy and clinical feasibility deserve consideration in translation of research outcomes. This study evaluated the feasibility of rehabilitation programs within the context of a large randomized controlled trial of physical therapy. Ambulant participants with Parkinson's disease (PD) (n = 210) were randomized into three groups: (1) progressive strength training (PST); (2) movement strategy training (MST); or (3) control ("life skills"). PST and MST included fall prevention education. Feasibility was evaluated in terms of safety, retention, adherence, and compliance measures. Time to first fall during the intervention phase did not differ across groups, and adverse effects were minimal. Retention was high; only eight participants withdrew during or after the intervention phase. Strong adherence (attendance >80%) did not differ between groups (P = .435). Compliance in the therapy groups was high. All three programs proved feasible, suggesting they may be safely implemented for people with PD in community-based clinical practice.


Comparison of oral ampicillin and doxycycline in the treatment of uncomplicated gonorrhoea.
An account is given of a computer-processed 1-year study comprising 1,124 patients (625 males and 499 females) with uncomplicated gonorrhoea. Alternate patients were treated with either two oral doses of 1 g. ampicillin 5 hours apart, or 0.3 g. doxycycline in a single oral dose. Ampicillin remained as efficacious as in 1968 to 1970, in both males and females, in whom the failure rates were 1.1 and 1 per cent. respectively. After doxycycline the failure rate was 8.1 per cent. in males, 5.7 per cent. in females, and 7.1 per cent. overall. Ampicillin was significantly better than doxycycline in the treatment of men (P less than 0.001) as well as of women (0.05 greater than P greater than 0.01). 89.7 per cent. (29/29) of the relapses in doxycycline-treated patients occurred in those harbouring strains sensitive to tetracycline. Sensitivity to doxycycline followed the pattern of tetracycline sensitivity. Thus sensitivity tests with these antibiotics provided no practical aid to therapy. The high incidence of nausea and vomiting in patients treated with doxycycline (12 per cent.) makes it inadvisable to increase the dose; instead, multiple doses are necessary to obtain satisfactory results. There were very few adverse reactions to ampicillin; a rash occurred in only three patients (0.5 per cent.). In the group treated with doxycycline, 31.5 per cent. of the patients infected by streptomycin-resistant strains relapsed compared with only 1.8 per cent. of patients infected by streptomycin-sensitive strains. This difference is highly significant (P less than 0.001). Thus the sensitivity of gonococcal strains to streptomycin in vitro may serve as a valuable guide to the likely outcome of treatment with tetracyclines.


Monitoring bone strontium intake in osteoporotic females self-supplementing with strontium citrate with a novel in-vivo X-ray fluorescence based diagnostic tool.
Ten female volunteers were recruited as part of the Ryerson and McMaster University Strontium (Sr) in Bone Research Study to have their bone Sr levels measured as they self-supplemented with Sr supplements of their choice. Of the ten volunteers, nine were suffering from osteopenia and/or osteoporosis. Non-invasive bone Sr measurements were performed using an in vivo x-ray fluorescence (IVXRF) I-125 based system. Thirty minute measurements were taken at the finger and ankle, representing primarily cortical and trabecular bone, respectively. For analysis, the 14.2keV Sr K-alpha peak normalized to the Coherent peak at 35.5keV was used. Baseline readings, representing natural bone Sr levels were acquired since all volunteers had no previous intake of Sr based supplements or medications. Once Sr supplements were started, a 24h reading was taken, followed by frequent measurements ranging from weekly, biweekly to monthly. The longest volunteer participation was 1535days. The mean baseline Sr signal observed for the group was 0.42±0.13 and 0.39±0.07 for the finger and ankle, respectively. After 24h, the mean Sr signal rose to 1.43±1.12 and 1.17±0.51, for the finger and ankle, respectively, representing a statistically significant increase (p=0.0043 & p=0.000613). Bone Sr levels continued to increase throughout the length of the study. However the Sr signal varied widely between the individuals such that after three years, the highest Sr signal observed was 28.15±0.86 for the finger and 26.47±1.22 for the ankle in one volunteer compared to 3.15±0.15 and 4.46±0.36, for the finger and ankle, respectively in another. Furthermore, while it was previously reported by our group, that finger bone Sr levels may plateau within two years, these results suggest otherwise, indicating that bone Sr levels will continue to rise at both bone sites even after 4years of Sr intake.


Amplification and overexpression of the dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 2 (DYRK2) gene in esophageal and lung adenocarcinomas.
Genomic amplification can lead to the activation of cellular proto-oncogenes during tumorigenesis, and is observed in most, if not all, human malignancies, including adenocarcinomas of lung and esophagus. Using a two-dimensional restriction landmark genomic scanning technique, we identified five NotI/HinfI fragments with increased genomic dosage in an adenocarcinoma of the gastroesophageal junction. Four of these amplified fragments were matched within three contigs of chromosome 12 using the bioinformatics tool, Virtual Genome Scan. All three of the contigs map to the 12q13-q14 region, and the regional amplification in the tumor was verified using comparative genomic hybridization analysis. The 12q14 amplicon was characterized using sequence tagged site-amplification mapping with DNA from paired normal-tumor tissues of 75 gastroesophageal and 37 lung adenocarcinomas. The amplicon spans a region of >12 Mb between genes DGKA and BLOV1. The core-amplified domain was determined to be <0.5 Mb between marker WI-12457 and gene IFNG. However, MDM2, a well-documented oncogene of the region, is outside the core-domain. Eleven genes and expressed sequence tags within the amplicon were selected for quantitative reverse transcription-PCR, and DYRK2, a member of the dual-specificity kinase family, was overexpressed in all of the tumors showing gene amplification. Among the sequence tagged site/expressed sequence tag/gene markers tested, DYRK2 demonstrated the highest DNA copy number and the highest level of mRNA overexpression in the tumors. Moreover, DYRK2 mRNA overexpression (>2.5-fold of normal mean) was found in 18.6% of additional 86 lung adenocarcinomas in an assay using oligonucleotide microarrays. DYRK2 mRNA overexpression occurs more frequently than gene amplification in both esophageal and lung adenocarcinomas. This is the first report of amplification and overexpression of DYRK2 in any tumor type.


Anti-Proliferative Potential of Cynaroside and Orientin-In Silico (DYRK2) and In Vitro (U87 and Caco-2) Studies.
Luteolin derivates are plant compounds with multiple benefits for human health. Stability to heat and acid hydrolysis and high resistance to (auto)oxidation are other arguments for the laden interest in luteolin derivates today. The present study was designed to compare the in silico and in vitro anti-proliferative potential of two luteolin derivates, luteolin-7-O-glucoside/cynaroside (7-Lut) and luteolin-8-C-glucoside/orientin (8-Lut). In silico investigations were carried out on the molecular target, namely, the human dual specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) in association with its natural ligand, curcumin (PDB ID: 5ZTN), by CLC Drug Discovery Workbench v. 1.5.1. software and Molegro Virtual Docker (MVD) v. MVD 2019.7.0. software. In vitro studies were performed on two human tumor cell lines, glioblastoma (U87) and colon carcinoma (Caco-2), respectively. Altogether, docking studies have revealed 7-Lut and 8-Lut as effective inhibitors of DYRK2, even stronger than the native ligand curcumin; in vitro studies indicated the ability of both luteolin glucosides to inhibit the viability of both human tumor cell lines, up to 85% at 50 and 100 µg/mL, respectively; the most augmented cytotoxic and anti-proliferative effects were obtained for U87 exposed to 7-Lut (IC50 = 26.34 µg/mL). The results support further studies on cynaroside and orientin to create drug formulas targeting glioblastoma and colon carcinoma in humans.


Recent Progress in the Study of Peroxiredoxin in the Harmful Algal Bloom Species Chattonella marina.
Peroxiredoxin (Prx) is a relatively recently discovered antioxidant enzyme family that scavenges peroxides and is known to be present in organisms from biological taxa ranging from bacteria to multicellular eukaryotes, including photosynthetic organisms. Although there have been many studies of the Prx family in higher plants, green algae, and cyanobacteria, few studies have concerned raphidophytes and dinoflagellates, which are among the eukaryotic algae that cause harmful algal blooms (HABs). In our proteomic study using 2-D electrophoresis, we found a highly expressed 2-Cys peroxiredoxin (2-CysPrx) in the raphidophyte Chattonella marina var. antiqua, a species that induces mass mortality of aquacultured fish. The abundance of the C. marina 2-CysPrx enzyme was highest in the exponential growth phase, during which photosynthetic activity was high, and it then decreased by about a factor of two during the late stationary growth phase. This pattern suggested that 2-CysPrx is a key enzyme involved in the maintenance of high photosynthesis activity. In addition, the fact that the depression of photosynthesis by excessively high irradiance was more severe in the 2-CysPrx low-expression strain (wild type) than in the normal-expression strain (wild type) of C. marina suggested that 2-CysPrx played a critical role in protecting the cell from oxidative stress caused by exposure to excessively high irradiance. In the field of HAB research, estimates of growth potential have been desired to predict the population dynamics of HABs for mitigating damage to fisheries. Therefore, omics approaches have recently begun to be applied to elucidate the physiology of the growth of HAB species. In this review, we describe the progress we have made using a molecular physiological approach to identify the roles of 2-CysPrx and other antioxidant enzymes in mitigating environmental stress associated with strong light and high temperatures and resultant oxidative stress. We also describe results of a survey of expressed Prx genes and their growth-phase-dependent behavior in C. marina using RNA-seq analysis. Finally, we speculate about the function of these genes and the ecological significance of 2-CysPrx, such as its involvement in circadian rhythms and the toxicity of C. marina to fish.


Cloning and characterization of LCB1, a Saccharomyces gene required for biosynthesis of the long-chain base component of sphingolipids.
The existence of auxotrophic mutants of Saccharomyces cerevisiae having an absolute requirement for the long-chain base (lcb) component of sphingolipids suggests that sphingolipids are crucial for viability and growth. One mutant, termed the lcb1-1 mutant, lacks the activity of serine palmitoyltransferase, the first enzyme in the pathway for long-chain base synthesis. Here, we present evidence that LCB1 has been molecularly cloned. The size of the LCB1 transcript, the direction of transcription, and transcription initiation sites were determined. In addition, the coding region and its 5' and 3' flanking regions were sequenced. Analysis of the DNA sequence revealed a single open reading frame of 1,674 nucleotides, encoding a predicted peptide of 558 amino acids. The hydropathy profile of the predicted peptide suggests a hydrophobic, globular, membrane-associated protein with two potential transmembrane helices. Comparison of the predicted amino acid sequence to known protein sequences revealed homology to 5-aminolevulinic acid synthase and to 2-amino-3-ketobutyrate coenzyme A ligase. These homologies, the similarity of the chemical reactions catalyzed by the three enzymes, and the finding that LCB1 restores serine palmitoyltransferase activity to an lcb1-defective strain indicate that serine palmitoyltransferase or a subunit of the enzyme is the most likely product of LCB1. Homology of the LCB1 predicted protein to the Escherichia coli biotin synthetase was also observed, but the biological significance of this observation is not clear. A role for sphingolipids in sporulation is implicated by our finding that diploids homozygous for lcb1 failed to sporulate.


Transgenerational impact of intimate partner violence on methylation in the promoter of the glucocorticoid receptor.
Prenatal exposure to maternal stress can have lifelong implications for psychological function, such as behavioral problems and even the development of mental illness. Previous research suggests that this is due to transgenerational epigenetic programming of genes operating in the hypothalamic-pituitary-adrenal axis, such as the glucocorticoid receptor (GR). However, it is not known whether intrauterine exposure to maternal stress affects the epigenetic state of these genes beyond infancy. Here, we analyze the methylation status of the GR gene in mothers and their children, at 10-19 years after birth. We combine these data with a retrospective evaluation of maternal exposure to intimate partner violence (IPV). Methylation of the mother's GR gene was not affected by IPV. For the first time, we show that methylation status of the GR gene of adolescent children is influenced by their mother's experience of IPV during pregnancy. As these sustained epigenetic modifications are established in utero, we consider this to be a plausible mechanism by which prenatal stress may program adult psychosocial function.


Role of hypoxia inducible factor-1α for interferon synthesis in mouse dendritic cells.
Dendritic cells (DCs) are an important link between innate and adaptive immunity. DCs get activated in inflamed tissues where oxygen tension is usually low, which requires the transcription factor hypoxia inducible factor (HIF)-1 for cellular adaptation. To investigate whether the HIF-1 transcriptional complex plays a pivotal role in the function of DCs, we compared the effects of exogenous inflammatory stimuli and hypoxia on HIF-1α in bone marrow-derived DCs from wild type and myeloid-specific HIF-1α knock-out mice. We showed that the Toll-like receptor ligands lipopolysaccharides and cytosine-phosphatidyl-guanines significantly induce HIF-1α mRNA and protein, leading to elevated HIF-1 target gene expression of vascular endothelial growth factor. In contrast, polyinosinic:polycytidylic acid did not show comparable effects. Furthermore the potential to up-regulate inflammatory cytokines critically influences DC function. Our data demonstrate that HIF-1α protein is needed for adequate production of interferon-α and -β. In co-cultures of DCs and cytotoxic T cells, we observed that DCs lacking active HIF-1α protein induce significantly less CD278 and granzyme B mRNA in T cells. We conclude that HIF-1α plays a crucial role in DC interferon production and T cell activation, linking the innate and adaptive immune system.


Kinetics of facial motoneuron loss following facial nerve transection in severe combined immunodeficient mice.
We have recently shown that cells of the acquired immune system are crucial components of motoneuron survival after injury (Serpe et al. [1999] J. Neurosci. 19:RC7). The goal of the present study was to determine the kinetics of facial motoneuron (FMN) loss in wild-type, scid, and reconstituted scid mice after a right facial nerve axotomy at the stylomastoid foramen. Scid mice showed a significant decrease in FMN survival at all weekly postoperative (wpo) times. One, two, four, and ten wpo, ipsilateral FMN survival in scid mice was 90% +/- 1.8%, 84% +/- 1.3%, 52% +/- 3.7%, and 45% +/- 2.5%, respectively, of the contralateral, unoperated side. In contrast, FMN loss after axotomy in wild-type and reconstituted scid mice was not observed until 4 wpo (86% +/- 2.5% and 83% +/- 3.5%, respectively) relative to the contralateral, unoperated side. However, the levels of FMN in both wild-type and reconstituted scid mice were significantly higher than those in the nonreconstituted scid at 4 wpo. By 10 wpo, FMN survival in both wild-type and reconstituted scid mice had continued to decline significantly (60% +/- 2.1% and 58% +/- 3.1%, respectively) relative to the contralateral, unoperated side but were still significantly higher than that of the nonreconstituted scid at 10 wpo. Several important controls were also added to this study. Because the scid mutation is present in all cells (although it specifically results in a loss of V(D)J recombination mechanisms, we wanted to rule out the actual DNA mutation as causal in FMN loss). To accomplish this, we used the recombinase-activating gene-2 knockout (RAG-2 KO) mouse model, in which the RAG-2 has been disrupted and prevents maturation of T and B cells. As with the scid model, there was a significant loss of FMN at 4 wpo in the RAG-2 KO that could be reversed with whole splenocyte reconstitution. We also compared FMN numbers in nonaxotomized facial nuclei from both scid and RAG-2 KO mice relative to wild-type controls. No differences in normal numbers of FMN were found in either the mutation or the gene knockout model. The ability of T and B lymphocytes to rescue FMN from cell death after peripheral nerve injury supports the hypothesis that cells of the acquired immune system produce neurotrophic factors or neurocytokines to support neuronal survival until target reconnection occurs.


Alkali-metal- and halide-free dinuclear mixed-valent samarium and europium complexes.
We describe the synthesis of mixed-valent (Ln(ii)/Ln(iii)) dilanthanide complexes supported by a calix[4]pyrrole ligand. The complexes are obtained by one-electron reduction of Ln(iii)/Ln(iii) complexes and are alkali-metal- and halide-free. The complexes are designed to activate small molecules by taking advantage of both the base and the one-electron reductant contained in their structure. We demonstrate a proof-of-principle concept of this mechanism by activating water and silanol.


Associations between recollected rates of Category D fruit machine use as a child and adult gambling in a young adult sample.
There have been recent restrictions to the range of gambling products made available to UK children, with the industry association Bacta introducing a minimum age of 18 for Category D fruit machines, which can otherwise be legally used by children. Any potential government action on Category D fruit machines may want to consider limitations in the current evidence base. The present study addressed this issue, by conceptually replicating previous results associating recollected usage of Category D fruit machine usage as a child and adult gambling. Compared to previous studies, the present study used a younger adult sample, and also tested for potential moderation by subjective confidence. Three out of four main tested associations were significant and in the hypothesised direction, and a lack of significance on interaction terms yielded no evidence of potential moderation by subjective confidence. The present study therefore added to the limited evidence base on potential risks of legal Category D fruit machine usage as a child.


Intracellular localization of phosphatidylinositide 3-kinase and insulin receptor substrate-1 in adipocytes: potential involvement of a membrane skeleton.
Phosphatidylinositide (PI) 3-kinase binds to tyrosyl-phosphorylated insulin receptor substrate-1 (IRS-1) in insulin-treated adipocytes, and this step plays a central role in the regulated movement of the glucose transporter, GLUT4, from intracellular vesicles to the cell surface. PDGF, which also activates PI 3-kinase in adipocytes, has no significant effect on GLUT4 trafficking in these cells. We propose that this specificity may be mediated by differential localization of PI 3-kinase in response to insulin versus PDGF activation. Using subcellular fractionation in 3T3-L1 adipocytes, we show that insulin- and PDGF-stimulated PI 3-kinase activities are located in an intracellular high speed pellet (HSP) and in the plasma membrane (PM), respectively. The HSP is also enriched in IRS-1, insulin-stimulated tyrosyl-phosphorylated IRS-1 and intracellular GLUT4-containing vesicles. Using sucrose density gradient sedimentation, we have been able to segregate the HSP into two separate subfractions: one enriched in IRS-1, tyrosyl-phosphorylated IRS-1, PI 3-kinase as well as cytoskeletal elements, and another enriched in membranes, including intracellular GLUT4 vesicles. Treatment of the HSP with nonionic detergent, liberates all membrane constituents, whereas IRS-1 and PI 3-kinase remain insoluble. Conversely, at high ionic strength, membranes remain intact, whereas IRS-1 and PI 3-kinase become freely soluble. We further show that this IRS-1-PI 3-kinase complex exists in CHO cells overexpressing IRS-1 and, in these cells, the cytosolic pool of IRS-1 and PI 3-kinase is released subsequent to permeabilization with Streptolysin-O, whereas the particulate fraction of these proteins is retained. These data suggest that IRS-1, PI 3-kinase, as well as other signaling intermediates, may form preassembled complexes that may be associated with the actin cytoskeleton. This complex must be in close apposition to the cell surface, enabling access to the insulin receptor and presumably other signaling molecules that somehow confer the absolute specificity of insulin signaling in these cells.


Ecklonia cava Polyphenol Has a Protective Effect against Ethanol-Induced Liver Injury in a Cyclic AMP-Dependent Manner.
Previously, we showed that Ecklonia cava polyphenol (ECP) treatment suppressed ethanol-induced increases in hepatocyte death by scavenging intracellular reactive oxygen species (ROS) and maintaining intracellular glutathione levels. Here, we examined the effects of ECP on the activities of alcohol-metabolizing enzymes and their regulating mechanisms in ethanol-treated hepatocytes. Isolated hepatocytes were incubated with or without 100 mM ethanol. ECP was dissolved in dimethylsulfoxide. ECP was added to cultured cells that had been incubated with or without ethanol. The cells were incubated for 0-24 h. In cultured hepatocytes, the ECP treatment with ethanol inhibited cytochrome P450 2E1 (CYP2E1) expression and activity, which is related to the production of ROS when large quantities of ethanol are oxidized. On the other hand, ECP treatment with ethanol increased the activity of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase. These changes in activities of CYP2E1 and ADH were suppressed by treatment with H89, an inhibitor of protein kinase A. ECP treatment with ethanol enhanced cyclic AMP concentrations compared with those of control cells. ECP may be a candidate for preventing ethanol-induced liver injury via regulating alcohol metabolic enzymes in a cyclic AMP-dependent manner.


Grading meningioma: a comparative study of thallium-SPECT and FDG-PET.
The purpose was to compare capability of fluorine-18 fluorodeoxyglucose (FDG)-PET and thallium-201 (Tl)-SPECT for grading meningioma.This retrospective study was conducted as a case-control study under approval by the institutional review board. In the hospital information system, 67 patients (22 men and 45 women) who had both FDG-PET and Tl-SPECT preoperative examinations were found with histopathologic diagnosis of meningioma. The maximum FDG uptake values of the tumors were measured, and they were standardized to the whole body (SUVmax) and normalized as gray matter ratio (SUVRmax). Mean and maximum Tl uptake ratios (TURmean and TURmax, respectively) of the tumors were measured and normalized as ratios to those of the contralateral normal brain. Receiver-operating characteristic curve analyses of the 4 indexes were conducted for differentiation between low- and high-grade meningiomas, and areas under the curves (AUCs) were compared. Correlation coefficients were calculated between these indexes and Ki-67.Fifty-six meningiomas were classified as grade I (low grade), and 11 were grade II or III (high grade). In all 4 indexes, a significant difference was observed between low- and high-grade meningiomas (P < 0.05). AUCs were 0.817 (SUVmax), 0.781 (SUVRmax), 0.810 (TURmean), and 0.831 (TURmax), and no significant difference was observed among the indexes. Their sensitivity and specificity were 72.7% to 90.9% and 71.4% to 87.5%, respectively. Correlation of the 4 indexes to Ki-67 was statistically significant, but coefficients were relatively low (0.273-0.355).Tl-SPECT, which can be used at hospitals without a cyclotron or an FDG distribution network, has high diagnostic capability of meningioma grades comparable to FDG-PET.


Characterization of radiation-induced cavernous malformations and comparison with a nonradiation cavernous malformation cohort.
The objective of this study was to characterize the clinical features of radiation-induced cavernous malformations (RICMs). The authors retrospectively reviewed the clinical and radiological characteristics of patients with RICMs. The features of these RICMs were then compared with features of nonradiation cavernous malformations (CMs) in 270 patients. Thirty-two patients with RICMs were identified (56.2% men), with a median age of 31.1 years at RICM diagnosis. The median latency from radiation treatment to RICM diagnosis was 12.0 years (interquartile range 5.0-19.6 years). RICMs were always within the previous radiation port. RICMs were symptomatic at diagnosis in 46.9%, and were associated with symptomatic intracranial hemorrhage at any time in 43.8%. Older age at the time of radiation treatment and higher radiation dose were associated with shorter latency. RICMs tended to be diagnosed at a younger age than nonradiation CMs (median 31.1 vs 42.4 years, respectively; p = 0.054) but were significantly less likely to be symptomatic at the time of diagnosis (46.9% vs 65.8%, respectively; p = 0.036). RICMs were more likely to be multiple CMs than nonradiation CMs (p = 0.0002). Prospectively, the risk of symptomatic hemorrhage was 4.2% for RICMs and 2.3% for nonradiation CMs per person-year (p = 0.556). In the absence of symptoms at presentation, the risk of hemorrhage for RICMs was higher than for nonradiation CMs (4.2% vs 0.35%, respectively; p = 0.118). In this patient population, RICMs occurred within the radiation port approximately 12 years after radiation treatment. Compared with nonradiation CMs, RICMs were more likely to occur as multiple CMs, to present at a younger age, and were at least as likely to cause symptomatic hemorrhage.


Perceived overqualification and health: a longitudinal analysis.
The authors examined the effects of perceived overqualification on health and health decline by means of a 2-wave panel study of members of a midwestern American Postal Workers Union local. The 1st hypothesis was that overqualification was negatively related to health at Time 2 (T2); the second hypothesis was that overqualification was positively related to perceived health decline at T2. Neither was supported by the data. However, the relationships were in the expected direction for perceived mismatch but not for the perceived no grow dimension of overqualification. The results imply that perceived no grow may have immediate threats to health, whereas perceived mismatch may have longer term implications for health. The stability of perceived health between Time 1 (T1) and T2 could overshadow a longitudinal effect of overqualification on health and health decline at T2.


Maximum fractal dimension of cerebral seizure remains constant through the course of electroconvulsive therapy.
Electroconvulsive therapy (ECT), in which electrical current is used to induce seizures, is an effective treatment in psychiatry. Different methods of analyzing the electroencephalogram (EEG) changes during ECT have been studied for predicting clinical outcome. Analysis of the fractal dimension (FD) is one such method. Mid-seizure and post-seizure FD has been shown to correlate with antidepressant effect. In this study, we examined whether the highest fractal dimension achieved during each ECT session changed over the course of 6 ECTs. The sample for this study came from a randomized controlled trial, comparing the efficacy of bifrontal and bitemporal electrode placements in schizophrenia. EEG was recorded using bilateral frontal pole leads during all ECT sessions. In 40 of the 114 randomized patients, we could obtain artifact-free EEGs for the first 6 ECT sessions. FD was calculated using standardized algorithms. For each session, the average of 5 highest FDs was calculated. The change in this value over a course of 6 ECTs was analyzed using repeated-measures analysis of variance. The average highest FD remained virtually unchanged across the 6 ECT sessions. Means (standard deviations) average maximum FDs over the 6 sessions were 1.57 (0.075), 1.57 (0.064), 1.56 (0.064), 1.57 (0.062), 1.55 (0.07), and 1.56 (0.067); occasion effect, F = 0.5, P = .75. Group effect (F = 0.01, P = .92) and group × occasion interaction effect (F = 1.88, P = .1) were not significant, suggesting no influence of electrode placement on maximum FD. Seizure duration, however, showed significant decline over the course of ECT. Maximum FD of ECT-induced EEG seizure remains fairly constant over frontal poles across the first 6 ECT sessions, which is true irrespective of ECT electrode placements.


Flattening maps for the visualization of multibranched vessels.
In this paper, we present two novel algorithms which produce flattened visualizations of branched physiological surfaces, such as vessels. The first approach is a conformal mapping algorithm based on the minimization of two Dirichlet functionals. From a triangulated representation of vessel surfaces, we show how the algorithm can be implemented using a finite element technique. The second method is an algorithm which adjusts the conformal mapping to produce a flattened representation of the original surface while preserving areas. This approach employs the theory of optimal mass transport. Furthermore, a new way of extracting center lines for vessel fly-throughs is provided.


Fatal Case of Burkholderia gladioli Pneumonia in a Patient With COVID-19.
Background: Burkholderia gladioli (B gladioli) is a rare, gram-negative rod that was initially regarded as a plant pathogen. However, B gladioli has been reported as the primary pathogen causing pneumonia in organ transplant recipients and in patients with cystic fibrosis. We report a case of bacterial pneumonia caused by B gladioli in a patient hospitalized for coronavirus disease 2019 (COVID-19). Case Report: A 68-year-old male was admitted for acute hypoxic respiratory failure secondary to COVID-19 pneumonia. He was treated with dexamethasone and convalescent plasma, resulting in improvement in the hypoxemia. However, during the latter part of his inpatient stay, the patient developed pneumonia caused by B gladioli. The isolate of B gladioli was sensitive to meropenem, levofloxacin, and trimethoprim/sulfamethoxazole and intermediate to ceftazidime. He was treated with meropenem and levofloxacin. Despite treatment, the patient developed acute respiratory distress syndrome with multiorgan failure, suffered cardiac arrest, and died. Conclusion: To the best of our knowledge, this case is the first report of B gladioli coinfection in a patient hospitalized for COVID-19 and provides insight into the possible detrimental outcome of B gladioli and COVID-19 coinfection.


Constant Load Pedaling Exercise Combined with Electrical Muscle Stimulation Leads to an Early Increase in Sweat Lactate Levels.
A novel exercise modality combined with electrical muscle stimulation (EMS) has been reported to increase cardiovascular and metabolic responses, such as blood lactate concentration. We aimed to examine the effect of constant load pedaling exercise, combined with EMS, by non-invasively and continuously measuring sweat lactate levels. A total of 22 healthy young men (20.7 ± 0.8 years) performed a constant load pedaling exercise for 20 min at 125% of the pre-measured ventilatory work threshold with (EMS condition) and without (control condition) EMS stimulation. Blood lactate concentration was measured by blood samples obtained from the earlobe every minute. Sweat lactate was monitored in real time using a sensor placed on the forearm. The sweat lactate threshold (sLT) was defined as the point of increase in sweat lactate. sLT occurred significantly earlier in the EMS condition than in the control condition. In the single regression analysis, the difference in sLT between the two conditions, as the independent variable, was a significant predictor of the difference in blood lactate concentrations at the end of the exercise (p < 0.05, r = −0.52). Sweat lactate measurement may be a noninvasive and simple alternative to blood lactate measurement to determine the effectiveness of exercise combined with EMS.


Routine antenatal syphilis screening in South west Nigeria- a questionable practice.
Untreated maternal syphilis is strongly associated with adverse birth outcomes, especially in women with high titre syphilis. The WHO recommends routine serological screening in pregnancy. Some workers have advised a reappraisal of this practice, having demonstrated low sero-prevalence in their antenatal population. In view of this, the aim of this study was to determine the seroprevalence of syphilis in the antenatal population presenting at a major hospital in south-west Nigeria. This was a cross sectional study of healthy pregnant Nigerian women attending Adeoyo Maternity Hospital in the capital of Oyo State. The case record of every pregnant woman presenting for their first antenatal clinic visit over a 4-month period (September 1st to December 31st 2006) was reviewed. During the study period, two thousand six hundred and seventy-eight women sought antenatal care. Three hundred and sixty-nine women (369; 13.4%) had incomplete records and were excluded from analysis. The records of the 2,318(86.6%) women with adequate records were subsequently reviewed. The mean age of the women was 27.4 years (± 5.34) and the mean gestational age 26.4 weeks (±6.36). The modal parity was 0. Only three patients were found to be reactive for syphilis giving a prevalence of 0.13%. The sero- prevalence value in this study is quite low and may justify the call to discontinue routine antenatal syphilis screening. However, a more rigorous screening program using diagnostic tests with higher sensitivity maybe necessary before jettisoning this traditional aspect of antenatal care.


Stethoscope disinfection campaign in a Nigerian teaching hospital:results of a before-and-after study.
This study aimed to assess the impact of a stethoscope disinfection sensitization campaign among doctors and nurses in a Nigerian teaching hospital. The design was a before-and-after study. Pre-program measurements were used to provide a baseline against which the post-program results were compared. Interventions that promoted compliance with stethoscope disinfection practice that were implemented included training and education on stethoscope disinfection and introduction of 70% isopropyl alcohol disinfectant at points-of-care places. Microbiological assessment of stethoscopes used by health workers was conducted after the intervention and the outcome was compared with the pilot study results. After the intervention, of the 89 stethoscopes screened, 18 (20.2%) were contaminated with bacterial agents. A higher prevalence of stethoscope contamination was observed among stethoscopes from the intensive care unit (66.7%), the VIP unit (50%), and the antenatal unit (37.5%). The main isolates were Staphylococcus aureus (44.4%) and Escherichia coli (50%). The antibiotic sensitivity assessment indicated that the bacterial isolates were resistant to nearly all the antibiotics tested. All the 89 health workers whose stethoscopes were screened after the intervention admitted to cleaning their stethoscopes after seeing each patient, representing a compliance rate of 100%, unlike the 15% compliance at the pilot phase. The baseline stethoscope contamination rate was 78.5% versus 20.2% post-intervention. Training and education and introduction of alcohol-based disinfectants inexpensive but very effective methods to improve stethoscope disinfection compliance among health workers in low-income settings.


Effect of monensin inclusion on intake, digestion, and ruminal fermentation parameters by Bos taurus indicus and Bos taurus taurus steers consuming bermudagrass hay.
Effects of monensin inclusion and cattle subspecies on utilization of bermudagrass hay (13.7% CP, 77.3% NDF, and 38.8% ADF) were evaluated using ruminally cannulated steers (5 [BI] and 5 [BT]; 398 kg BW). Subspecies were concurrently subjected to a 2-period, 2-treatment crossover design. Treatments were 0 (CON) or 200 mg·steer·d monensin (MON) in 0.91 kg dried distillers' grains with solubles. Periods were 70 d in length: 20 d of adaptation, 22 d of sample collection, and 28 d for withdrawal of treatment. Steers were group housed during adaptation and moved to individual covered pens for sampling. Hay, ort, and fecal grab samples were collected d 21 through 25 for determination of intake and digestion. Ruminal fluid was collected with a suction strainer 0, 2, 4, 8, and 12 h after feeding on d 42 for pH, VFA, and ruminal NH-N (RAN) analysis. Additionally, at h 2, ruminal fluid and contents were collected for determination of rate of NH production and CH production rate. No subspecies × monensin interactions were observed ( ≥ 0.12). Monensin had no effect ( ≥ 0.16) on intake or digestibility parameters. No subspecies effect ( ≥ 0.11) was observed for forage OM intake, total OM intake, or OM digestion. Total digestible OM intake tended to be greater ( = 0.06) for BT steers than for BI steers (14.0 vs. 12.2 g/kg BW). There was an effect of hour after feeding ( ≤ 0.01) on pH, total VFA, acetate:propionate ratio, and molar percent acetate and propionate. Total VFA concentration was greater ( = 0.01) in CON steers than in MON steers (66.5 vs. 62.0 m). Monensin decreased molar percent acetate ( = 0.02) from 72.5 to 71.2% and increased molar percent propionate ( < 0.01) from 16.9 to 18.7%, resulting in a reduced ( < 0.01) acetate:propionate ratio (from 4.34 to 3.85). Although not significantly ( = 0.19), monensin numerically reduced the CH production rate by 15.8%. Greater ( = 0.07) CH production rate tended to be observed in BI steers than in BT steers (21.4 vs. 16.6 μmol CH·mL·h, respectively). Monensin had no effect ( ≥ 0.32) on pH, RAN, or rate of NH production. A subspecies × hour after feeding interaction was observed for RAN, with BT having greater RAN at h 0 and 4, whereas BI had greater RAN at h 2, 8, and 12. Overall, monensin decreased the acetate:propionate ratio and total VFA concentration but had no effect on forage utilization. steers consumed less digestible OM and had a greater CH production rate compared with BT steers, suggesting BT were better able to utilize the available forage resource than BI.


Chemical speciation of individual airborne particles by the combined use of quantitative energy-dispersive electron probe X-ray microanalysis and attenuated total reflection Fourier transform-infrared imaging techniques.
In our previous work, it was demonstrated that the combined use of attenuated total reflectance (ATR) FT-IR imaging and quantitative energy-dispersive electron probe X-ray microanalysis (ED-EPMA), named low-Z particle EPMA, had the potential for characterization of individual aerosol particles. Additionally, the speciation of individual mineral particles was performed on a single particle level by the combined use of the two techniques, demonstrating that simultaneous use of the two single particle analytical techniques is powerful for the detailed characterization of externally heterogeneous mineral particle samples and has great potential for characterization of atmospheric mineral dust aerosols. These single particle analytical techniques provide complementary information on the physicochemical characteristics of the same individual particles, such as low-Z particle EPMA on morphology and elemental concentrations and the ATR-FT-IR imaging on molecular species, crystal structures, functional groups, and physical states. In this work, this analytical methodology was applied to characterize an atmospheric aerosol sample collected in Incheon, Korea. Overall, 118 individual particles were observed to be primarily NaNO(3)-containing, Ca- and/or Mg-containing, silicate, and carbonaceous particles, although internal mixing states of the individual particles proved complicated. This work demonstrates that more detailed physiochemical properties of individual airborne particles can be obtained using this approach than when either the low-Z particle EPMA or ATR-FT-IR imaging technique is used alone.


Persistent paramyxovirus infections and behaviour of beta-adrenergic receptors in C-6 rat glioma cells.
This paper describes the influence of persistent infections of C-6 rat glioma cells by paramyxoviruses [virus of subacute sclerosing panencephalitis (SSPE) and canine distemper (CDV)] on the cellular beta-adrenergic membrane receptors. The number and binding properties of the beta-adrenergic receptors of the paramyxovirus-infected cells were measured by 3H-dihydroalprenolol binding studies and compared with those of the uninfected C-6 cells. In the case of SSPE virus neither changes in number nor binding properties of beta-adrenergic receptors could be observed, whereas in the case of CDV persistence the number of beta-adrenergic receptors was reduced to about 50%, without an apparent influence on the binding constant for the ligand to the receptors.


Longitudinal association between ideal cardiovascular health status and muscular fitness in adolescents: The LabMed Physical Activity Study.
Muscular fitness is an emerging predictor for cardiovascular disease mortality. The ideal cardiovascular health metrics has been inversely related to a subsequent cardiometabolic health in adulthood. However, evidence regarding muscular fitness and ideal cardiovascular health in adolescents is scarce. This study aimed to examine the longitudinal association between ideal cardiovascular health index and muscular fitness. This study cohort consisted of 331 adolescents (183 girls) from the LabMed Physical Activity Study who were followed from 2011 to 2013. Ideal cardiovascular health, as defined by the American Heart Association, was determined as meeting ideal health factors (total cholesterol, blood pressure, and glucose) and behaviors (smoking status, body mass index, physical activity, and diet). Handgrip strength and standing long jump tests assessed muscular fitness and were transformed into standardized values according to age and sex. ANCOVA showed a significant association between the accumulation of ideal cardiovascular health metrics at baseline and muscular fitness indices at follow-up (F(4, 322) = 2.280, p = 0.04). In addition, the higher the number of ideal cardiovascular health metrics accumulated, the higher the likelihood of having a high muscular fitness over a two-year period (p for trend = 0.01), after adjustments for age, sex, pubertal stage and socioeconomic status and muscular fitness at baseline. The ideal cardiovascular health status during adolescence was associated with high muscular fitness levels over a two-year period.


The human and animal baby schema effect: correlates of individual differences.
We investigated the animal and human baby schema effect (BSE) in relation to gender, parental status, and individual features. In three, independent online surveys, conducted during three consecutive years, (Ntotal=1389), ratings of photographs of human and animal infants as well as of adults, sociodemographic variables (age, gender, parental status) and personality attributes (empathy, attachment, interpersonal closeness, narcissism, and need to belong) were assessed. We demonstrated that humans are sensitive to the baby schemata of both humans and animals and that both are weakly positively correlated. BSE is positively associated with female gender and (affective) empathy. Higher interpersonal closeness and need to belong were additionally connected specifically to the human BSE. In contrast, narcissism and insecure attachment were not related to the BSE, suggesting a robustness of this phenomenon to possible negative influences of these two personality attributes.


[Aspiration of dental implant -- reasons, management and prevention].
Aspiration of foreign bodies is extremely rare in adults, but it may occur during the course of dental treatment and become a serious problem for the patient. A case of a 77-year old man with chronic cough after dental treatment and unrecognised aspiration of an implant is presented. The implant remained unidentified for three years as an endobronchial foreign body of the lower lobe bronchus. A bronchoscopic removal failed and surgery was indicated for lobectomy of the right lower lobe because of chronic pneumonia. A review of prevention, signs and symptoms, management and documentation of the complications is presented.


Astroglial networks scale synaptic activity and plasticity.
Astrocytes dynamically interact with neurons to regulate synaptic transmission. Although the gap junction proteins connexin 30 (Cx30) and connexin 43 (Cx43) mediate the extensive network organization of astrocytes, their role in synaptic physiology is unknown. Here we show, by inactivating Cx30 and Cx43 genes, that astroglial networks tone down hippocampal synaptic transmission in CA1 pyramidal neurons. Gap junctional networking facilitates extracellular glutamate and potassium removal during synaptic activity through modulation of astroglial clearance rate and extracellular space volume. This regulation limits neuronal excitability, release probability, and insertion of postsynaptic AMPA receptors, silencing synapses. By controlling synaptic strength, connexins play an important role in synaptic plasticity. Altogether, these results establish connexins as critical proteins for extracellular homeostasis, important for the formation of functional synapses.


Macrophages transfer mitochondria to sensory neurons to resolve inflammatory pain.
The current paradigm is that inflammatory pain passively resolves following the cessation of inflammation. Yet, in a substantial proportion of patients with inflammatory diseases, resolution of inflammation is not sufficient to resolve pain, resulting in chronic pain. Mechanistic insight into how inflammatory pain is resolved is lacking. Here, we show that macrophages actively control resolution of inflammatory pain remotely from the site of inflammation by transferring mitochondria to sensory neurons. During resolution of inflammatory pain in mice, M2-like macrophages infiltrate the dorsal root ganglia that contain the somata of sensory neurons, concurrent with the recovery of oxidative phosphorylation in sensory neurons. The resolution of pain and the transfer of mitochondria requires expression of CD200 receptor (CD200R) on macrophages and the non-canonical CD200R-ligand iSec1 on sensory neurons. Our data reveal a novel mechanism for active resolution of inflammatory pain.


Long-term care and the private insurance market.
Increased life expectancy and the aging of the baby boom generation will bring rapid growth in the number of people at risk of needing long-term care (LTC). This Issue Brief provides an overview of the current LTC financing and delivery system in the United States, focusing on private-sector initiatives to meet the United States' LTC needs. It discusses private-sector plan design--particularly employment-based plan design--providing an in-depth look at the dramatic changes taking place in the private-sector LTC market since its inception in the early and mid 1980s. Aside from informal care provided in the community, the current system of financing LTC depends largely on the Medicaid program and individual financing. Issues confronting this system include spiraling costs associated with LTC services that may threaten beneficiaries' access to care. Other issues include the potential depletion of personal assets and a bias toward institutionalization (which may not always provide the most cost-effective or desired type of care available). Many leaders regard private long-term care insurance (LTCI) as a way to increase access to financing and as a potential alternative to Medicaid and out-of-pocket financing. By the end of 1993, a total of 3.4 million private-sector LTCI policies had been sold, up from approximately 815,000 in 1987. While the majority of these plans were sold to individuals or through group associations, employment-based plans accounted for a significant proportion of this growth. Premiums for LTCI vary substantially based on age and plan design. Insurers generally attempt to set premiums such that they will remain level over the insured's lifetime. However, because little LTC claims insurance experience yet exists, the actuarial basis for developing premiums and statutory reserves is limited. Several bills over the last three Congresses have been introduced to address the issue of LTC. However, due to cost implications and lack of consensus regarding the optimum overall structure required to finance and deliver care, broad legislation to expand coverage--particularly public coverage--is not likely in the near term.


Effect of Body Mass Index on Postoperative Complications in Beating Coronary Artery Surgery.
Body Mass Index (BMI) is considered as an important risk factor in cardiovascular surgery. We designed a historical cohort study for the evaluation of perioperative complications related to BMI in patients who underwent off-pump coronary artery bypass grafting (OPCAB). We studied 1120 consecutive patients who underwent OPCAB between January 2008 and December 2011 in Imam Ali Hospital, Kermanshah, Iran. Patients were divided into four groups according to BMI: underweight/low BMI (< 18.5 kg/m2), healthy weight (between 18.5 kg/m2 and 24.9 kg/m2), overweight/high BMI (between 25 kg/m2 and 30 kg/m2), and obese/very high BMI (> 30 kg/m2). In multivariable regression analysis, an important correlation between the underweight/low BMI group and mortality was observed (p=0.037). Postoperative stroke, postoperative atrial fibrillation (AF) and intra-aortic balloon pump (IABP) use were not associated with BMI. In linear regression analysis, significant correlations between low BMI, reintubation, ICU stay time and intubation time were found. Re-exploration for bleeding was significantly correlated with having a low or high BMI. Having a low BMI (which is association with malnutrition and respiratory muscles weakness) was significantly associated with reintubation, prolonged intubation time and ICU stay time. The obese group was also associated with postoperative atelectasia and fever.


Genetic skin diseases with altered aging.
Integration, homeostasis, and redundancy of function are hallmarks of important biological processes. Individual gene defects may overcome and override normal homeostatic systems and lead to dramatic, recognizable phenotypes by profoundly altering 1 or more physiological systems. Classical human geneticists interested in a monogenetic disease began at the level of altered function and struggled to determine the genomic defect of that disease. In the past 1 1/2 decades, many monogenetic defects have been identified by positional cloning, and the abnormal gene has been characterized. A challenge for current investigators is to understand how a genetic defect, identified by a DNA mutation, leads to the altered phenotype. This effort is not trivial, since there are multiple metabolic and structural consequences of a single altered gene. Further complexity results from individual genetic changes being modified by the genetic diversity of the human host. Pleiotropy refers to the phenomenon of multiple phenotypic effects of a single gene.


L-Borneol promotes skin flap survival by regulating HIF-1α/NF-κB pathway.
The clinical application of skin flaps in surgical reconstruction is frequently impeded by the occurrence of distant necrosis. L-Borneol exhibits myogenic properties in traditional Chinese medicine and is used in clinical settings to promote wound healing and conditions such as stroke. Nevertheless, the precise mechanism by which borneol exerts its protective effects on skin flap survival remains unclear. To explore the potential of L-borneol to promote skin flap survival and elucidate the underlying mechanisms. Thirty-six male Sprague-Dawley rats were randomly divided into three groups: a high-dose (200 mg/kg L-borneol per day), a low-dose (50 mg/kg/day), and control group (same volume of solvent). In each rat, a modified rectangular McFarlane flap model measuring 3 × 9 cm was constructed. Daily intragastric administration of L-borneol or solvent was performed. The flap was divided into three square sections of equal size, namely Zone I (the proximal zone), Zone II (the intermediate zone), and Zone III (the distal zone). The survival rate was quantified, and the histological state of each flap was evaluated on the seventh day following the surgical procedure. The assessment of angiogenesis was conducted using lead oxide/gelatin angiography, whereas the evaluation of blood flow in the free flap was performed using laser Doppler flow imaging. Superoxide dismutase activity was detected using the water-soluble tetrazolium salt-8 method. The quantities of vascular endothelial growth factor, interleukin (IL)-1β, IL-6, and tumour necrosis factor-α were determined using immunohistochemistry. The levels of nuclear transcription factor-κB, hypoxia-inducible factor-1, B-cell lymphoma-2 (BCL-2), and BCL-2-associated X (BAX) were determined by Western blotting technique. Flap survival rate significantly improved and neutrophil recruitment and release were enhanced after treatment with the compound. Angiogenesis was promoted. L-borneol protected against oxidative stress by increasing superoxide dismutase activity and decreasing malondialdehyde content. It downregulated the hypoxia-inducible factor nuclear transcription factor-κB pathway, leading to the inhibition of several inflammatory factors. Simultaneously, it facilitated the expression of vascular endothelial growth factor and BCL-2. The study shows that L-borneol may promote skin flap survival by inhibiting HIF-1α/NF-κB pathway.


Health Care Evolution Is Driving Staffing Industry Transformation.
The powerful transformation in the health care industry is reshaping not only patient care delivery and the business of health care but also demanding new strategies from vendors who support the health care system. These new strategies may be most evident in workforce solutions and health care staffing services. Consolidation of the health care industry has created increased demand for these types of services. Accommodating a changing workforce and related pressures resulting from health care industry transformation has produced major change within the workforce solutions and staffing services sector. The effect of the growth strategy of mergers, acquisitions, and organic development has revealed organizational opportunities such as expanding capacity for placing physicians, nurses, and allied professionals, among other workforce solutions. This article shares insights into workforce challenges and solutions throughout the health care industry.