Enhancing mitochondrial calcium buffering capacity reduces aggregation of misfolded SOD1 and motor neuron cell death without extending survival in mouse models of inherited amyotrophic lateral sclerosis.
Mitochondria have been proposed as targets for toxicity in amyotrophic lateral sclerosis (ALS), a progressive, fatal adult-onset neurodegenerative disorder characterized by the selective loss of motor neurons. A decrease in the capacity of spinal cord mitochondria to buffer calcium (Ca(2+)) has been observed in mice expressing ALS-linked mutants of SOD1 that develop motor neuron disease with many of the key pathological hallmarks seen in ALS patients. In mice expressing three different ALS-causing SOD1 mutants, we now test the contribution of the loss of mitochondrial Ca(2+)-buffering capacity to disease mechanism(s) by eliminating ubiquitous expression of cyclophilin D, a critical regulator of Ca(2+)-mediated opening of the mitochondrial permeability transition pore that determines mitochondrial Ca(2+) content. A chronic increase in mitochondrial buffering of Ca(2+) in the absence of cyclophilin D was maintained throughout disease course and was associated with improved mitochondrial ATP synthesis, reduced mitochondrial swelling, and retention of normal morphology. This was accompanied by an attenuation of glial activation, reduction in levels of misfolded SOD1 aggregates in the spinal cord, and a significant suppression of motor neuron death throughout disease. Despite this, muscle denervation, motor axon degeneration, and disease progression and survival were unaffected, thereby eliminating mutant SOD1-mediated loss of mitochondrial Ca(2+) buffering capacity, altered mitochondrial morphology, motor neuron death, and misfolded SOD1 aggregates, as primary contributors to disease mechanism for fatal paralysis in these models of familial ALS.


Subarachnoid block with low dose of bupivacaine and sufentanil in patients with coronary artery disease.
Subarachnoid block with local anesthetics and opioids enable efficacious spinal anesthesia because of their synergistic effect and permit the use of low-dose local anesthetics, which results in a stable hemodynamic state. The purpose of this study was to describe the cardiovascular effects of spinal anesthesia with low-dose bupivacaine and sufentanil on patients with coronary artery disease. This study was a double-blind randomized clinical trial. A total of 18 patients who had known coronary artery disease were enrolled. Our subjects underwent spinal block for lower limb surgery with 7.5 mg hyperbaric bupivacaine 0.5% and 5 µg sufentanil. Complications related to anesthesia such as hypotension, bradycardia, vasopressor need, and blood or volume use were recorded. The average mean arterial pressure decreased 15% in the first 15 min of spinal block in our cases. No patients presented with hypotension and the subjects were without complaints during the spinal anesthesia. All patients remained alert, and no ST segment changes were observed intraoperatively and until 6 h after the operation. Baseline ejection fraction (EF) 40% or less was observed in 10 patients and these subjects were compared with other patients. Systolic and diastolic blood pressures, mean arterial pressure, and heart rate decreased during the first 15 min in response to spinal anesthesia in both groups of patients, but decreased more significantly in patients with EF > 40%. We recommend spinal block with low-dose bupivacaine and sufentanil in patients with coronary artery disease and especially in patients with low EF.


A systematic review of parasites and micropredators of non-avian reptiles (Reptilia=Sauropsida) in Chile.
Knowledge about the identity of parasites in vertebrates is relevant because of their influence on ecological processes and health of their hosts. This is particularly important for groups of animals currently facing conservation issues, such as reptiles. The diversity of species and supra-specific taxa of microparasites and macroparasites (such as helminths and arthropods) present in non-avian reptiles in Chile was analyzed through a systematic review. A total of 49 scientific documents (thesis projects, abstracts in congresses, book chapters and peer-reviewed articles) concerning parasites, taxonomic descriptions and parasite ecology were included in this review. The suborder Iguania was among the most studied group with 35 native species recognized as hosts of parasites and 39 species of parasites reported up to the category of species or genus. Liolaemus tenuis was the species with the most taxa of recorded parasites (11 taxa, and only three to species level), but Liolaemus chillanensis had the highest number of identified species of parasites. In addition, only one native species of Serpentes, one of Gymnophthalmoidea, and two of Gekkota, as well as some reports of exotic species, were recorded as hosts. Among parasites, Trombidiformes was the richest order with 10 species from the superfamily Pterygosomatoidea and 16 species from Trombiculoidea. Current knowledge about the richness of helminths is very limited and there were only a few records of microparasites. In general, there is an urgent need for the development of collaborative works between specialists in reptile taxonomy and epidemiology in parasitology destined to evaluate the consequences that reptiles and their parasites will suffer due to the ongoing processes of habitat loss, climate change and the still present taxonomic issues of the native reptiles.


Transient receptor potential vanilloid 4 promotes cutaneous wound healing by regulating keratinocytes and fibroblasts migration and collagen production in fibroblasts in a mouse model.
Transient receptor potential vanilloid 4 (TRPV4), a cation ion channel, is expressed in different cells, and it regulates the development of different diseases. We recently found a high TRPV4 expression in the wounded skin area. However, the role of TRPV4 in cutaneous wound healing is unknown. To investigate the role of TRPV4 in cutaneous wound healing in a mouse model. Skin wound healing experiment and histopathological studies were performed between WT and TRPV4 KO mice. The effect of TRPV4 antagonist and agonist on cell migration, proliferation, and differentiation were examined in vitro. TRPV4 expression was enhanced in wounded area in the skin. TRPV4 KO mice had impaired cutaneous wound healing compared with the WT mice. Further, they had significantly suppressed re-epithelialization and formation of granulation tissue, amount of collagen deposition, and number of α-SMA-positive myofibroblasts in skin wounds. qPCR revealed that the KO mice had decreased mRNA expression of COL1A1 and ACTA2 in skin wounds. In vitro, treatment with selective TRPV4 antagonist suppressed migrating capacity, scratch stimulation enhanced the expression of phospho-ERK in keratinocytes, and TGF-β stimulation enhanced the mRNA expression of COL1A1 and ACTA2 in fibroblasts. Selective TRPV4 agonist suppressed cell migration in keratinocytes, and did not enhance proliferation and migration, but promoted differentiation in fibroblasts. TRPV4 mediates keratinocytes and fibroblasts migration and increases collagen deposition in the wound area, thereby promoting cutaneous wound healing.


Bifactor Model of the Sport Concussion Assessment Tool Symptom Checklist: Replication and Invariance Across Time in the CARE Consortium Sample.
Identifying separate dimensions of concussion symptoms may inform a precision medicine approach to treatment. It was previously reported that a bifactor model identified distinct acute postconcussion symptom dimensions. To replicate previous findings of a bifactor structure of concussion symptoms in the Concussion Assessment Research and Education (CARE) Consortium sample, examine measurement invariance from pre- to postinjury, and evaluate whether factors are associated with other clinical and biomarker measures. Cohort study (Diagnosis); Level of evidence, 2. Collegiate athletes were prospectively evaluated using the Sport Concussion Assessment Tool-3 (SCAT-3) during preseason (N = 31,557); 2789 were followed at <6 hours and 24 to 48 hours after concussion. Item-level SCAT-3 ratings were analyzed using exploratory and confirmatory factor analyses. Bifactor and higher-order models were compared for their fit and interpretability. Measurement invariance tested the stability of the identified factor structure across time. The association between factors and criterion measures (clinical and blood-based markers of concussion severity, symptom duration) was evaluated. The optimal structure for each time point was a 7-factor bifactor model: a General factor, on which all items loaded, and 6 specific factors-Vestibulo-ocular, Headache, Sensory, Fatigue, Cognitive, and Emotional. The model manifested strict invariance across the 2 postinjury time points but only configural invariance from baseline to postinjury. From <6 to 24-48 hours, some dimensions increased in severity (Sensory, Fatigue, Emotional), while others decreased (General, Headache, Vestibulo-ocular). The factors correlated with differing clinical and biomarker criterion measures and showed differing patterns of association with symptom duration at different time points. Bifactor modeling supported the predominant unidimensionality of concussion symptoms while revealing multidimensional properties, including a large dominant General factor and 6 independent factors: Headache, Vestibulo-ocular, Sensory, Cognitive, Fatigue, and Emotional. Unlike the widely used SCAT-3 symptom severity score, which declines gradually after injury, the bifactor model revealed separable symptom dimensions that have distinct trajectories in the acute postinjury period and different patterns of association with other markers of injury severity and outcome. The SCAT-3 total score remains a valuable, robust index of overall concussion symptom severity, and the specific factors identified may inform management strategies. Because some symptom dimensions continue to worsen in the first 24 to 48 hours after injury (ie, Sensory, Fatigue, Emotional), routine follow-up in this time frame may be valuable to ensure that symptoms are managed effectively.


Diagnostic confusion caused by hepatitis C: hemochromatosis presenting as rheumatoid arthritis.
We describe a patient with hemochromatosis and coexistent infection with the hepatitis C virus who was initially thought to have rheumatoid arthritis. His symptoms began at the age of 44 with pain of the hand joints, shoulders, hips, and knees and a positive rheumatoid factor. Four years later, he required replacement of both hips due to severe hip arthritis. Abnormalities in liver function were noted early on, but they were attributed to infection with the hepatitis C virus, detected serologically and by polymerase chain reaction amplification in the blood. The correct diagnosis was delayed until a decision to use methotrexate as treatment for his arthritis led to a liver biopsy, which revealed increased iron deposition consistent with hemochromatosis, confirmed by genetic testing, which revealed that the patient was homozygous for the C282Y mutation of the HLA-H gene.


Complete nucleotide sequence of Colorado tick fever virus segments M6, S1 and S2.
The nucleotide sequences of the tenth (M6), eleventh (S1) and twelfth (S2) dsRNA genomic segments of the Florio strain (N-7180) of Colorado tick fever virus were determined and found to be 675, 998 and 1884 bp, respectively, in length. A nonanucleotide motif and a hexanucleotide motif were found to be highly conserved in the 5' and 3' non-coding regions (NCRs), respectively, of the three segments. The first and last three nucleotides of each segment were of inverted complementarity, and segment-specific inverted terminal repeats were detected in the NCRs of the three segments. These findings suggest the occurrence of intracellular panhandle structures for the RNA transcripts. A readthrough phenomenon is suspected in segment M6. The environment surrounding the opal codon (position 1052-1054) of segment M6 conforms to that of leaky opal codons described in the literature.


Effects of Berberine against Pancreatitis and Pancreatic Cancer.
The pancreas is a glandular organ with endocrine and exocrine functions necessary for the maintenance of blood glucose homeostasis and secretion of digestive enzymes. Pancreatitis is characterized by inflammation of the pancreas leading to temporary or permanent pancreatic dysfunction. Inflammation and fibrosis caused by chronic pancreatitis exacerbate malignant transformation and significantly increase the risk of developing pancreatic cancer, the world's most aggressive cancer with a 5-year survival rate less than 10%. Berberine (BBR) is a naturally occurring plant-derived polyphenol present in a variety of herbal remedies used in traditional medicine to treat ulcers, infections, jaundice, and inflammation. The current review summarizes the existing in vitro and in vivo evidence on the effects of BBR against pancreatitis and pancreatic cancer with a focus on the signalling mechanisms underlying the effects of BBR.


Malignant lymphoma of the thyroid gland.
Malignant lymphoma of the thyroid gland is a rare entity; only 200 cases have been reported to date since 1960. Four patients with this disease presented at the Kingston clinic of the Ontario Cancer Treatment and Research Foundation. Those with localized malignant lymphoma, particularly the histiocytic types, responded favourably to resection of as much of the tumour as possible and subsequent local radiation with cobalt-60 telecurietherapy (3000 to 4000 rads in 3 to 4 weeks). The results of local radiation alone after a biopsy in patients with inoperable localized diseases are encouraging; it is possible, but not yet established, that some of these patients are cured. It has been suggested that the tumour is dependent on thyroid-stimulating hormone but conclusive evidence is not yet available.


Quantitative Intracranial Atherosclerotic Plaque Characterization at 7T MRI: An Ex Vivo Study with Histologic Validation.
In recent years, several high-resolution vessel wall MR imaging techniques have emerged for the characterization of intracranial atherosclerotic vessel wall lesions in vivo. However, a thorough validation of MR imaging results of intracranial plaques with histopathology is still lacking. The aim of this study was to characterize atherosclerotic plaque components in a quantitative manner by obtaining the MR signal characteristics (T1, T2, T2*, and proton density) at 7T in ex vivo circle of Willis specimens and using histopathology for validation. A multiparametric ultra-high-resolution quantitative MR imaging protocol was performed at 7T to identify the MR signal characteristics of different intracranial atherosclerotic plaque components, and using histopathology for validation. In total, 38 advanced plaques were matched between MR imaging and histology, and ROI analysis was performed on the identified tissue components. Mean T1, T2, and T2* relaxation times and proton density values were significantly different between different tissue components. The quantitative T1 map showed the most differences among individual tissue components of intracranial plaques with significant differences in T1 values between lipid accumulation (T1 = 838 ± 167 ms), fibrous tissue (T1 = 583 ± 161 ms), fibrous cap (T1 = 481 ± 98 ms), calcifications (T1 = 314 ± 39 ms), and the intracranial arterial vessel wall (T1 = 436 ± 122 ms). Different tissue components of advanced intracranial plaques have distinguishable imaging characteristics with ultra-high-resolution quantitative MR imaging at 7T. Based on this study, the most promising method for distinguishing intracranial plaque components is T1-weighted imaging.


Development of a novel multi-functional active membrane capping barrier for the remediation of nitrobenzene-contaminated sediment.
A novel bio-reactive capping barrier composed of polysulfone/granular activated carbon (PS/GAC) hybrid membranes immobilized with microorganism was developed for the remediation of nitrobenzene in sediments. The SEM observation demonstrated that all the membranes had a dense top layer and a porous sublayer, this structure can block the transfer of nitrobenzene from sediment to the water and enhance nitrobenzene degradation. Adsorption behaviors of nitrobenzene on membranes showed that the membrane impregnated with GAC had better performance than the pure PS membrane. The values of Kads increased from 4.64 (without GAC) to 6.19 (1:2 GAC). 20mg/L nitrobenzene can be completely degraded by Pseudomonas putida immobilized on membranes. The biodegradation rate of activated carbon-filled membrane system was little higher than that of pure PS membrane system. For remediation experiments, only about 21.7, 28.3 and 43.9% of nitrobenzene in the sediment was removed by the end of the experiments for PS/GAC membrane, sand-alone and sand amended with activated carbon capping systems, respectively. While for PS/GAC+microorganisms capping system, more than 70% of nitrobenzene loss was observed. This demonstrated that nitrobenzene can be effectively removed from contaminated sediments by microbial degradation in the bio-reactive capping system.


Single-stage anterior cruciate ligament revision with bone-patellar tendon-bone: a case-control series of revision of failed synthetic anterior cruciate ligament reconstructions.
The purpose of this study was to investigate the clinical results of single-stage revision anterior cruciate ligament reconstruction (ACLR) after synthetic ligament failure. The subjects comprised 20 patients who underwent revision ACLR after synthetic ligament failure. All revisions were performed with bone-patellar tendon-bone graft, and bone tunnel expansion after removal of synthetic materials was treated with bone plugs sized and trimmed as necessary to fill the bone tunnels. Clinical results were assessed at a mean of 2.8 years postoperatively, followed by comparison with the results of 20 primary ACLRs selected as case-matched controls. Assessment included the Lysholm score, International Knee Documentation Committee (IKDC) evaluation, instrumented laxity testing, and radiologic examination. Bone tunnel enlargement to 11 mm in diameter or greater was found in 10 of 20 revision ACLRs. However, favorable anteroposterior stability was obtained at final follow-up (1.4 +/- 2.0 mm in revision ACLR group and 1.5 +/- 1.5 mm in primary ACLR group). The overall Lysholm score improved significantly from preoperatively to final follow-up, but the revision ACLR group showed significantly worse results for the pain parameter than the primary ACLR group. The final IKDC results also showed significant postoperative improvement, but the number of cases with grade C was significantly higher in the revision ACLR group than in the primary ACLR group, which was attributed to radiologically confirmed osteoarthritis in the revision ACLR group. Single-stage revision ACLR with bone-patellar tendon-bone graft after synthetic ligament failure yielded favorable results in terms of IKDC grade, Lysholm score, and anteroposterior stability, despite enlarged bone tunnels after removal of synthetic material. Inferior results for the radiologic and pain parameters of the IKDC and Lysholm scores were attributed to osteoarthritic changes inherent to the revision ACLR group. Level III, therapeutic case-control study.


IL-4 Downregulates IL-1β and IL-6 and Induces GATA3 in Psoriatic Epidermal Cells: Route of Action of a Th2 Cytokine.
Clinical improvement of psoriasis induced by IL-4 treatment has been ascribed to changes in dermal inflammatory cells, such as activation of Th2 cells and tolerization of dendritic cells by suppressing IL-23 production. The pathologic epidermal alterations in psoriatic lesional skin include increased epidermal expression of IL-1β, IL-6, S100A7, and human β-defensin 2 (hBD2) and a downregulated expression of the epidermal transcription factor GATA3. Effects of IL-4 on the epidermal compartment of psoriasis lesions were not previously investigated. Therefore, we investigated whether IL-4 directly affects abovementioned psoriatic markers in the epidermal compartment. We cultured freshly isolated psoriatic epidermal cells, whole psoriatic and healthy skin biopsies, human keratinocytes and Langerhans cells with IL-4. The secretion of IL-1β and IL-6 by psoriatic epidermal cells was inhibited by IL-4 via transcriptional and posttranscriptional mechanisms, respectively. In normal skin, IL-4 inhibited IL-1β- and IL-17A-induced hBD2 expression in vitro. In addition, IL-4 reduced the protein expression of hBD2 in psoriatic skin biopsies and induced phospho-STAT6 protein. Epidermal GATA3 mRNA and protein were significantly upregulated by IL-4 in epidermal cells and keratinocytes. Our data argue that IL-4 improves psoriasis not only via modification/induction of Th2 cells and type II dendritic cells, but also via direct inhibition of inflammatory cytokines in resident IL-4R-expressing epidermal cells and thereby alters the psoriatic skin phenotype toward a healthy skin phenotype.


Evaluation of the impact and need for use of a safety guidewire during ureteroscopy.
The routine use of a "safety" guidewire adjacent to the ureteroscope during upper tract endoscopy is advocated in surgical texts and by many endourologists. Our experience has led us to theorize that a safety guidewire complicates ureteroscopy by providing resistance to introduction of the endoscope and by creating an obstruction to ureteroscopic instrumentation. To examine our theory, we developed a porcine animal model to evaluate the impact of the presence of a safety guidewire and reviewed our clinical experience, which routinely does not use a safety guidewire during ureteroscopy. An ex vivo model was created using the excised urinary tract of freshly slaughtered pigs. The forces needed to advance both a semirigid and flexible ureteroscope in the ureter were measured with and without the presence of a 0.035-inch safety guidewire. The clinical records of all patients undergoing ureteroscopy over a 4-year period were reviewed. On average, an additional 12 and 20 g of force were needed to introduce the semirigid and flexible ureteroscope when a guidewire was present. For the chosen study period, 361 patients underwent ureteroscopic procedures without the placement of a safety guidewire. No patient experienced an intraoperative complication related to the absence of a safety wire. The presence of a safety guidewire adjacent to the endoscope inhibits passage of the ureteroscope in an in vitro animal model. Technologic advancements in ureteroscope design and use of the holmium laser lithotrite minimize ureteral trauma and obviate the need for routine use of a safety wire during ureteroscopy.


A road traffic injury surveillance system using combined data sources in Peru.
A national hospital-based nonfatal road traffic injury surveillance system was established at sentinel units across Peru in 2007 under the leadership of the Ministry of Health. Surveillance data are drawn from three different sources (hospital records, police reports, and vehicle insurance reports) and include nonfatal road traffic injuries initially attended at emergency rooms. A single data collection form is used to record information about the injured, event characteristics related to the driver of the vehicle(s), and the vehicle(s). Data are analyzed periodically and disseminated to all surveillance system participants. Results indicated young adult males (15-29 years old) were most affected by nonfatal road traffic injuries and were most often the drivers of the vehicles involved in the collision. Four-wheeled vehicle occupants comprised one-half of cases in most regions of the country, and pedestrians injured in the event accounted for almost another half. The system established in Peru could serve as a model for the use of multiple data sources in national nonfatal road traffic injury surveillance. Based on this study, the challenges of this type of system include sustaining and increasing participation among sentinel units nationwide and identifying appropriate prevention interventions at the local level based on the resulting data.


Ideal Cardiovascular Health and Cognitive Test Performance: Testing a Modified Index of Life's Simple 7 Among Older Chinese Adults.
Evidence suggests that cognitive decline in older adults is influenced by cardiovascular health (CVH), with metabolic and vascular mechanisms hypothesized to underlie the etiology of cognitive impairment. Research in high-income nations suggests that improved CVH is linked with decreased cognitive impairment risk, but it is unclear if this pattern is evident in low-income countries. Nationally-representative data collected in China were drawn from the World Health Organization's Study on global AGing and adult health Wave 1 (2007-2010; n = 11,295). Seven CVH factors were classified as "ideal" or "not ideal": smoking and drinking frequency, body mass index, physical activity level, blood pressure, diet, and self-reported anxiety. Additionally, scores from five cognitive performance tests (immediate and delayed verbal recall, forward and backward digit span, verbal fluency) were used to create a composite cognitive function variable. Linear regression analyses tested whether ideal CVH measures were associated with higher composite cognitive performance, controlling for sociodemographic factors. As hypothesized, ideal CVH was generally associated with higher cognitive performance. Low anxiety levels and reliable access to sufficient food (including produce) were particularly associated with higher cognitive function. These results suggest early detection and controlling modifiable CVH risks may protect aging individuals in China from cognitive decline.


Allogeneic peripheral blood stem cell transplantation from two- or three-loci-mismatched related donors in adult Japanese patients with high-risk hematologic malignancies.
With the increasing frequency of haploidentical transplantation, it is becoming more important to establish the degree of HLA mismatch that can be accepted. We retrospectively analyzed clinical data of 50 adult Japanese patients with high-risk hematologic malignancies who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from two- or three-loci-mismatched related donors with HLA class I and II gene disparities in the graft-versus-host direction. They were treated at 20 transplant centers between 1996 and 2002. In all, 18 patients received unmanipulated PBSC, while 32 received purified CD34+ blood cells. Conventional (n=31) or reduced-intensity (n=19) conditioning regimens were used. Of the 39 patients (78%) who survived for > or =28 days after transplant, 37 (95%) achieved neutrophil engraftment, while graft failure and rejection occurred in two of 39 (5%) and three of 37 (8%) patients, respectively. Stepwise Cox regression analysis revealed a significantly lower incidence of grades II-IV acute GVHD in patients receiving purified CD34+ cells (hazard ratio 0.32; 95% CI 0.12-0.84; P=0.022). By 1 year post transplant, 28 patients (56%) had died of transplant-related problems, including infectious complications (30%). Although the number of patients is small, our data suggest that transplant-related problems, particularly infectious complications, are major obstacles to the success of this therapy.


In Silico Identification of Novel Immunogenic Secreted Proteins of Mycoplasma bovis from Secretome Data and Experimental Verification.
Mycoplasma bovis is a major pathogen, responsible for bovine respiratory diseases worldwide. The present lack of effective control measures leaves cattle owners at considerable perpetual risk of M. bovis outbreaks. In this study, we identified M. bovis secreted immunogenic proteins in silico as potential candidates for novel diagnostic agents and vaccines. We used immunoinformatics to analyze 438 M. bovis proteins previously identified with a label-free proteomics analysis of virulent M. bovis HB0801 (P1) and its attenuated P150 strains. The subcellular localization of these proteins was preliminarily screened and 59 proteins were found to be secreted extracellular proteins. Twenty-seven of these proteins contained a large number of predictive T-cell epitopes presented by major histocompatibility complex (MHC) class I and II molecules. Twenty-two of these 27 proteins had a high number of conformational B-cell epitopes, predicted from the corresponding 3D structural templates, including one unique to P1, two unique to P150, and 19 common to both strains. Five proteins were selected for further validation, and two of these, MbovP274 and MbovP570, were successfully expressed and purified. Both were confirmed to be secretory and highly immunogenic proteins that induced a mouse antibody response, reacted with cattle serum positive for M. bovis infection, and significantly increased the production of interleukin 8 (IL-8), IL-12 and interferon γ (IFN-γ) during the secretion of these three cytokines by both M. bovis mutants of these genes. These results should be useful in the development of novel immunological agents against M. bovis infection.


Diurnal and developmental changes in energy allocation of absorbed light at PSII in field-grown rice.
The allocation of absorbed light energy in PSII to electron transport and heat dissipation processes in rice grown under waterlogged conditions was estimated with the lake model of energy transfer. With regard to diurnal changes in energy allocation, the peak of the energy flux to electron transport, J(PSII), occurred in the morning and the peak of the energy flux to heat dissipation associated with non-photochemical quenching of Chl fluorescence, J(NPQ), occurred in the afternoon. With regard to seasonal changes in energy allocation, J(PSII) in the rapidly growing phase was greater than that in the ripening phase, even though the leaves of rice receive less light in the growing phase than in the ripening period in Japan. This seasonal decrease in J(PSII) was accompanied by an increase in J(NPQ). One of the reasons for the lower J(PSII) in the ripening phase might be a more sever afternoon suppression of J(PSII). To estimate energy dissipation due to photoinhibition of PSII, J(NPQ) was divided into J(fast), which is associated with fast-recovering NPQ mainly due to qE, and J(slow), which is mainly due to photoinhibition. The integrated daily energy loss by photoinhibiton was calculated to be about 3-8% of light energy absorption in PSII. Strategies for the utilization of light energy adopted by rice are discussed. For example, very efficient photosynthesis under non-saturating light in the rapidly growing phase is proposed.


[Recessive type of Freeman-Sheldon syndrome - report of two affected siblings]
OBJECTIVE: To share knowledge and information about the peculiarities of the Freeman-Sheldon syndrome, especially concerning the high risk of recurrence of its recessive type in siblings, and to stress the importance of genetic counseling for families after the birth of an affected child. DESCRIPTION: The authors describe and comment two pediatric cases of the Freeman-Sheldon syndrome in siblings born to healthy parents. These two cases present significant peculiarities that contradict the findings of the medical literature, obtained through bibliographic research about the subject. The cases described here corroborate the existence of a recessive type of the Freeman-Sheldon syndrome. In spite of the fact that some authors suggest a high frequency of severe neurological impairment in this type of syndrome, the two cases we analyzed did not show any apparent manifestation of such sequelae. COMMENTS: The Freeman-Sheldon syndrome is heterogeneous not only in its clinical presentation but also in its genetic transmission. It is very important to be informed about the existence of more than one form of hereditary transmission of this syndrome, since genetic counseling should take into consideration all possibilities. In these cases, the use of empiric risks of recurrence would be justified.


Definition of a core set of quality indicators for the assessment of HIV/AIDS clinical care: a systematic review.
Several organizations and individual authors have been proposing quality indicators for the assessment of clinical care in HIV/AIDS patients. Nevertheless, the definition of a consensual core set of indicators remains controversial and its practical use is largely limited. This study aims not only to identify and characterize these indicators through a systematic literature review but also to propose a parsimonious model based on those most used. MEDLINE, SCOPUS, Cochrane databases and ISI Web of Knowledge, as well as official websites of organizations dealing with HIV/AIDS care, were searched for articles and information proposing HIV/AIDS clinical care quality indicators. The ones that are on patient's perspective and based on services set were excluded. Data extraction, using a predefined data sheet based on Cochrane recommendations, was done by one of the authors while a second author rechecked the extracted data for any inconsistency. A total of 360 articles were identified in our search query but only 12 of them met the inclusion criteria. We also identified one relevant site. Overall, we identified 65 quality indicators for HIV/AIDS clinical care distributed as following: outcome (n=15) and process-related (n=50) indicators; generic (n=36) and HIV/AIDS disease-specific (n=29) indicators; baseline examinations (n=19), screening (n=9), immunization (n=4), prophylaxis (n=5), HIV monitoring (n=16), and therapy (=12) indicators. There are several studies that set up HIV clinical care indicators, with only a part of them useful to assess the HIV clinical care. More importantly, HIV/AIDS clinical care indicators need to be valid, reliable and most of all feasible.


Hedgehog-shaped {Mo368} cluster: unique electronic/structural properties, surfactant encapsulation and related self-assembly into vesicles and films.
The hedgehog-shaped {Mo368} cluster shows unique electronic (extremely high extinction coefficient) and structural features, especially regarding its size, the high number of delocalized electrons which allows to measure the surface enhanced Raman scattering (SERS) spectrum and the option for coordination chemistry inside the cavity. Its relative instability in aqueous solution can be overcome by embedment in a hydrophobic shell of dimethyldioctadecylammonium cations. The resulting hybrid self-assembles into spherical vesicles in acetone-water mixtures, according to a process directed by hydrophobic-hydrophilic interactions. It also forms rather stable Langmuir monolayers while a second layer evolves under higher surface pressure, in accordance with a rather low alkyl surface density.


Antibacterial peptides: basic facts and emerging concepts.
Antibacterial peptides are the effector molecules of innate immunity. Generally they contain 15-45 amino acid residues and the net charge is positive. The cecropin type of linear peptides without cysteine were found first in insects, whilst the defensin type with three disulphide bridges were found in rabbit granulocytes. Now a database stores more than 800 sequences of antibacterial peptides and proteins from the animal and plant kingdoms. Generally, each species has 15-40 peptides made from genes, which code for only one precursor. The dominating targets are bacterial membranes and the killing reaction must be faster than the growth rate of the bacteria. Some antibacterial peptides are clearly multifunctional and an attempt to predict this property from the hydrophobicity of all amino acid side chains are given. Gene structures and biosynthesis are known both in the fruit fly Drosophila and several mammals. Humans need two classes of defensins and the cathelicidin-derived linear peptide LL-37. Clinical cases show that deficiencies in these peptides give severe symptoms. Examples given are morbus Kostmann and atopic allergy. Several antibacterial peptides are being developed as drugs.


Immunoconjugates for Cancer Targeting: A Review of Antibody-Drug Conjugates and Antibody-Functionalized Nanoparticles.
Targeted therapy has been recently highlighted due to the reduction of side effects and improvement in overall efficacy and survival from different types of cancers. Considering the approval of many monoclonal antibodies in the last twenty years, cancer treatment can be accomplished by the combination of monoclonal antibodies and small molecule chemotherapeutics. Thus, strategies to combine both drugs in a single administration system are relevant in the clinic. In this context, two strategies are possible and will be further discussed in this review: antibody-drug conjugates (ADCs) and antibody-functionalized nanoparticles. First, it is important to better understand the possible molecular targets for cancer therapy, addressing different antigens that can selectively bind to antibodies. After selecting the best target, ADCs can be prepared by attaching a cytotoxic drug to an antibody able to target a cancer cell antigen. Briefly, an ADC will be formed by a monoclonal antibody (MAb), a cytotoxic molecule (cytotoxin) and a chemical linker. Usually, surface-exposed lysine or the thiol group of cysteine residues are used as anchor sites for linker-drug molecules. Another strategy that should be considered is antibody-functionalized nanoparticles. Basically, liposomes, polymeric and inorganic nanoparticles can be attached to specific antibodies for targeted therapy. Different conjugation strategies can be used, but nanoparticles coupling between maleimide and thiolated antibodies or activation with the addition of ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC)/ N-hydroxysuccinimide (NHS) (1:5) and further addition of the antibody are some of the most used strategies. Herein, molecular targets and conjugation strategies will be presented and discussed to better understand the in vitro and in vivo applications presented. Also, the clinical development of ADCs and antibody-conjugated nanoparticles are addressed in the clinical development section. Finally, due to the innovation related to the targeted therapy, it is convenient to analyze the impact on patenting and technology. Information related to the temporal evolution of the number of patents, distribution of patent holders and also the number of patents related to cancer types are presented and discussed. Thus, our aim is to provide an overview of the recent developments in immunoconjugates for cancer targeting and highlight the most important aspects for clinical relevance and innovation.


Long-Term Influence of Concussion on Cardio-Autonomic Function in Adolescent Hockey Players.
Concussion may negatively influence cardiovascular function and the autonomic nervous system, defined by alteration in heart rate variability (HRV). Differences in HRV most commonly emerge during a physical challenge, such as the final steps of the return-to-sport progression. To assess the effect of concussion history on aspects of cardio-autonomic function during recovery from a bout of submaximal exercise in adolescent male hockey athletes. Case-control study. Research laboratory. Thirty-three male athletes participating in Midget-AAA hockey were divided into those with (n = 15; age = 16 ± 1 years, height = 1.78 ± 0.06 m, mass = 73.9 ± 7.4 kg, 10.5 ± 1.6 years of sport experience, 25.2 ± 18.3 months since last injury) or without (n = 18; age = 16 ± 1 years, height = 1.78 ± 0.05 m, mass = 74.8 ± 7.6 kg, 10.6 ± 1.9 years of sport experience) a concussion history. Those with a concussion history were binned on total count: 1 concussion or 2 or more concussions. All athletes underwent 5 minutes of resting HRV assessment, followed by 20 minutes of aerobic exercise at 60% to 70% of their maximal target heart rate and a 9-minute, postexercise HRV assessment. Heart rate variability measures of mean NN interval, root mean square of successive differences, and standard deviation of NN interval (SDNN). Group demographic characteristics were not different. When the control and concussed groups were compared, group and time main effects for heart rate recovery, root mean square of successive differences, and SDNN (P values < .01), and an interaction effect for SDNN (P < .05) were demonstrated. Recovery trends for each group indicated that a history of 2 or more concussions may negatively affect cardio-autonomic recovery postexercise. Our findings suggest that those with more than 1 previous concussion may be associated with a greater risk for long-term dysautonomia. Future use of HRV may provide clinicians with objective guidelines for concussion-management and safe return-to-participation protocols.


Factors influencing attendance in a structured physical activity program for Aboriginal and Torres Strait Islander women in an urban setting: a mixed methods process evaluation.
Aboriginal and Torres Strait Islander women experience higher rates of obesity, chronic disease, and are less active than non-Indigenous Australian women. Lifestyle programs designed to increase physical activity and encourage healthy eating are needed to ameliorate this disparity. The aim of this study was to identify participants' perceived barriers and enablers to attend group exercise classes as part of a 12-week fitness program. To understand the factors that influence attendance, a mixed method process evaluation was undertaken in which a quantitative measure of attendance in the group exercise classes was used to identify cases for further qualitative investigation. Aboriginal and/or Torres Strait Islander women aged 18 to 64 years were recruited to a research trial of a fitness program. The 12-week program included two 60-minute group exercise classes per week, and four nutrition education workshops. Semi-structured interviews were conducted at program completion. Participants were stratified by attendance, and interviews from the highest and lowest 25 percentiles analysed. Rigour was strengthened through use of multiple data analysts, member checking and prolonged engagement in the field. Analyses of the post-program interviews revealed that participants enrolled in the program primarily for the perceived health benefits and all (with one exception) found the program met their needs and expectations. The atmosphere of classes was positive and comfortable and they reported developing good relationships with their fellow participants and program staff. Low attendees described more barriers to attendance, such as illness and competing work and family obligations, and were more likely to report logistical issues, such as inconvenient venue or class times. Attendance to the 'Aboriginal and Torres Strait Islander Women's Fitness Program' was primarily influenced by the participant's personal health, logistics and competing obligations. Low attendees reported more barriers during the 12-week period and identified fewer enabling factors than high attendees. Australian New Zealand Clinical Trials Registry ACTRN12610000224022.


Enhanced natural killer cell activity in experimental murine encephalitozoonosis.
Spleen cells from mice infected with the protozoan parasite Encephalitozoon cuniculi demonstrated enhanced in vitro cytolysis of YAC-1 lymphoma cells. Selective cell depletion experiments showed that the dominant cell population mediating cytolysis of YAC-1 tumor cells expressed the characteristic phenotype of murine natural killer (NK) cells because (i) pretreatment of spleen cells with anti-asialo GM 1 antiserum plus complement abolished the cytotoxic activity; (ii) augmented cytolysis was found in athymic nude mice; (iii) pretreatment of spleen cells with anti-Thy 1.2 plus complement did not affect the level of cytolysis; and (iv) nylon wool removal of adherent cells did not reduce the augmented cytolysis. The augmented cytolysis peaked 7 days after infection, gradually diminished, and finally returned to control levels by 21 days postinfection. The parasite-induced augmentation of NK cell activity was dose-dependent: inoculation of 10(7) parasites gave maximum enhancement, whereas 10(5) or 10(4) parasites had an insignificant effect on spontaneous NK cell cytolysis. The augmented NK cell cytotoxicity was dependent upon viable parasites; inoculation of killed parasites failed to stimulate a significant increase in spontaneous cytolysis. An active infectious process was an important component of this process. The peak of NK activity in euthymic mice was closely correlated with the active stage of infection, and reduction of NK cell activity coincided with recovery from infection. By contrast, athymic nude mice were unable to control E. cuniculi infections yet maintained persistently elevated NK responses. The present data, along with previous reports, indicate that infection with E. cuniculi evokes transient modulation of host immune functions.


Children's psychosocial state after the 2018 Lombok earthquake.
The current earthquake disaster in Lombok, Indonesia, in July 2018 has caused 564 deaths, and 445.343 were evacuated to refugee camps, including children. Disasters have the potential in resulting short-and long-term effects on the psychological functioning, emotional adjustment, health, and developmental trajectory of children. Nurses play a significant role when a disaster occurs. One of the nurses' roles is to give a traumatic healing intervention to the victims. This study sought to assess children's psychosocial state after the 2018 Lombok earthquake. A total of 189 children from five regencies in Lombok were selected to participate in the study using accidental sampling. Data were collected using the Strengths and Difficulties Questionnaire (SDQ). Descriptive statistics and cross-tabulation were used for data analysis. The participants consisted of 98 girls (51.9%) and 91 boys (48.1%), with the majority (n = 142 [75.1%]) being from school-aged children. The SDQ results showed that most of the children were at the abnormal stage for difficulties (n = 103 [54.5%]), and most of them were at a normal stage for strength (n = 97 [51.3%]). The cross-tabulation analysis revealed that gender might influence the SDQ score for the strength (p = 0.034), but not for difficulties (p = 0.482). However, age did not have a correlation with SDQ score, either for strength (p = 0.475) or difficulties (p = 0.836), respectively. The study found that children in Lombok generally displayed positive behavior and emotional progress after the earthquake. However, some children remained in distress and thus required more observation from parents or other social welfare agencies. This research may help nurses decide on their nursing care for children who experience disasters.


In vivo CD86 blockade inhibits CD4+ T cell activation, whereas CD80 blockade potentiates CD8+ T cell activation and CTL effector function.
To address whether a functional dichotomy exists between CD80 and CD86 in naive T cell activation in vivo, we administered anti-CD80 or CD86 blocking mAb alone or in combination to mice with parent-into-F(1) graft-vs-host disease (GVHD). In this model, the injection of naive parental T cells into unirradiated F(1) mice results in either a Th1 cytokine-driven, cell-mediated immune response (acute GVHD) or a Th2 cytokine-driven, Ab-mediated response (chronic GVHD) in the same F(1) recipient. Combined CD80/CD86 blockade beginning at the time of donor cell transfer mimicked previous results seen with CTLA4Ig and completely abrogated either acute or chronic GVHD by preventing the activation and maturation of donor CD4(+) T cells as measured by a block in acquisition of memory marker phenotype and cytokine production. Similar results were seen with selective CD86 blockade; however, the degree of CD4 inhibition was always less than that seen with combined CD80/CD86 blockade. A more striking effect was seen with selective CD80 blockade in that chronic GVHD was converted to acute GVHD. This effect was associated with the induction of Th1 cytokine production, donor CD8(+) T cell activation, and development of antihost CTL. The similarity of this effect to that reported for selective CTLA4 blockade suggests that CD80 is a critical ligand for CTLA4 in mediating the down-regulation of Th1 responses and CD8(+) T cell activation. In contrast, CD86 is critical for the activation of naive CD4(+) T cells in either a Th1 or a Th2 cytokine-mediated response.


Individual Differences in Impulsive Action Reflect Variation in the Cortical Serotonin 5-HT2A Receptor System.
Impulsivity is an important feature of multiple neuropsychiatric disorders, and individual variation in the degree of inherent impulsivity could play a role in the generation or exacerbation of problematic behaviors. Serotonin (5-HT) actions at the 5-HT2AR receptor (5-HT2AR) promote and 5-HT2AR antagonists suppress impulsive action (the inability to withhold premature responses; motor impulsivity) upon systemic administration or microinfusion directly into the medial prefrontal cortex (mPFC), a node in the corticostriatal circuit that is thought to play a role in the regulation of impulsive action. We hypothesized that the functional capacity of the 5-HT2AR, which is governed by its expression, localization, and protein/protein interactions (eg, postsynaptic density 95 (PSD95)), may drive the predisposition to inherent impulsive action. Stable high-impulsive (HI) and low-impulsive (LI) phenotypes were identified from an outbred rodent population with the 1-choice serial reaction time (1-CSRT) task. HI rats exhibited a greater head-twitch response following administration of the preferential 5-HT2AR agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) and were more sensitive to the effects of the selective 5-HT2AR antagonist M100907 to suppress impulsive action relative to LI rats. A positive correlation was observed between levels of premature responses and 5-HT2AR binding density in frontal cortex ([(3)H]-ketanserin radioligand binding). Elevated mPFC 5-HT2AR protein expression concomitant with augmented association of the 5-HT2AR with PSD95 differentiated HI from LI rats. The observed differential sensitivity of HI and LI rats to 5-HT2AR ligands and associated distinct 5-HT2AR protein profiles provide evidence that spontaneously occurring individual differences in impulsive action reflect variation in the cortical 5-HT2AR system.


Satellite DNA evolution in Corvoidea inferred from short and long reads.
Satellite DNA (satDNA) is a fast-evolving portion of eukaryotic genomes. The homogeneous and repetitive nature of such satDNA causes problems during the assembly of genomes, and therefore it is still difficult to study it in detail in nonmodel organisms as well as across broad evolutionary timescales. Here, we combined the use of short- and long-read data to explore the diversity and evolution of satDNA between individuals of the same species and between genera of birds spanning ~40 millions of years of bird evolution using birds-of-paradise (Paradisaeidae) and crow (Corvus) species. These avian species highlighted the presence of a GC-rich Corvoidea satellitome composed of 61 satellite families and provided a set of candidate satDNA monomers for being centromeric on the basis of length, abundance, homogeneity and transcription. Surprisingly, we found that the satDNA of crow species rapidly diverged between closely related species while the satDNA appeared more similar between birds-of-paradise species belonging to different genera.


Utilization of Large Data Sets in Maternal Health in Finland: A Case for Global Health Research.
In recent years, the use of large data sets, such as electronic health records, has increased. These large data sets are often referred to as "Big Data," which have various definitions. The purpose of this article was to summarize and review the utilization, strengths, and challenges of register data, which means a written record containing regular entries of items or details, and Big Data, especially in maternal nursing, using 4 examples of studies from the Finnish Medical Birth Register data and relate these to other international databases and data sets. Using large health register data is crucial when studying and understanding outcomes of maternity care. This type of data enables comparisons on a population level and can be utilized in research related to maternal health, with important issues and implications for future research and clinical practice. Although there are challenges connected with register data and Big Data, these large data sets offer the opportunity for timely insight into population-based information on relevant research topics in maternal health. Nurse researchers need to understand the possibilities and limitations of using existing register data in maternity research. Maternal child nurse researchers can be leaders of the movement to utilize Big Data to improve global maternal health.


Peri-implant health.
The aim is to define clinical and histologic characteristics of peri-implant tissues in health and describe the mucosa-implant interface. An understanding of the characteristics of healthy peri-implant tissues facilitates the recognition of disease (i.e., departure from health). The healthy peri-implant mucosa is, at the microscopic level, comprised of a core of connective tissue covered by either a keratinized (masticatory mucosa) or non-keratinized epithelium (lining mucosa). The peri-implant mucosa averages about 3 to 4 mm high, and presents with an epithelium (about 2 mm long) facing the implant surface. Small clusters of inflammatory cells are usually present in the connective tissue lateral to the barrier epithelium. Most of the intrabony part of the implant appears to be in contact with mineralized bone (about 60%), while the remaining portion faces bone marrow, vascular structures, or fibrous tissue. During healing following implant installation, bone modeling occurs that may result in some reduction of the marginal bone level. The characteristics of the peri-implant tissues in health are properly identified in the literature, including tissue dimensions and composition. Deviation from the features of health may be used by the clinician (and researcher) to identify disease, including peri-implant mucositis and peri-implantitis.


Improved small-sample estimation of nonlinear cross-validated prediction metrics.
When predicting an outcome is the scientific goal, one must decide on a metric by which to evaluate the quality of predictions. We consider the problem of measuring the performance of a prediction algorithm with the same data that were used to train the algorithm. Typical approaches involve bootstrapping or cross-validation. However, we demonstrate that bootstrap-based approaches often fail and standard cross-validation estimators may perform poorly. We provide a general study of cross-validation-based estimators that highlights the source of this poor performance, and propose an alternative framework for estimation using techniques from the efficiency theory literature. We provide a theorem establishing the weak convergence of our estimators. The general theorem is applied in detail to two specific examples and we discuss possible extensions to other parameters of interest. For the two explicit examples that we consider, our estimators demonstrate remarkable finite-sample improvements over standard approaches.


Non-functional expression of Escherichia coli signal peptidase I in Bacillus subtilis.
The Escherichia coli lep gene, encoding signal peptidase I (SPase I) was provided with Bacillus subtilis transcription/translation signals and expressed in this organism. When present on a low-copy-number plasmid, the amount of E. coli SPase I produced (per mg cell protein) in B. subtilis was half that produced in wild-type E. coli cells. The production of E. coli SPase I in B. subtilis was increased approximately fivefold by cloning the lep gene into a high-copy-number plasmid. The expression of E. coli SPase I in B. subtilis did not appear to increase the rate of processing of two hybrid secretory precursor proteins. Two observations may explain the failure of E. coli SPase I to stimulate processing of exported proteins in B. subtilis. First, the E. coli SPase I was apparently not exposed on the outside of the B. subtilis cytoplasmic membrane, indicating its incorrect insertion into the membrane. Second, in vitro processing studies, using cell-free extracts of B. subtilis producing E. coli SPase I, suggested that the enzyme was not active. A further outcome of this study was that conditions favouring processing of precursors by SPase I in cell-free extracts of E. coli did not favour processing by the corresponding enzyme in B. subtilis cell-free extracts. This suggests that significant differences exist between the two enzymes. The observation that antibodies directed against E. coli SPase I did not cross-react with B. subtilis membrane proteins supports this idea.


Paediatric inpatient setting: an evaluation of parental perspectives.
The Nursing and Midwifery Council (2008) define the standards of conduct, ethics and performance for nurses and midwives of nursing currently practicing in the UK. The Code places emphasis on the core nursing principles of kindness, respect, dignity and support for patients and relatives while under nursing care. A prospective study was conducted using a validated questionnaire to assess adherence to these core nursing principles on the basis of parental assessment in an orthopaedic paediatric inpatient unit at University Hospital Coventry and Warwickshire (UHCW). Core nursing standards were highest in respect to kindness' and 'respect' shown for patients (96% and 98% positive scores) and lowest for 'support' offered to their parents (89% positive scores). Lower 'support' scores possibly relate to information provision or emotional support. Improvement may be achieved via provision of additional time to identify parental concerns, which may be non-medical. The results demonstrate that parents perceive core nursing principles to be strongly adhered to on the orthopaedic paediatric unit at UHCW.


Effect of Different Root Canal Drying Protocols on the Bond Strength of Two Bioceramic Sealers.
This study evaluated in vitro the effect of two different drying protocols on the dentin bond strength of two different bioceramic sealers (Sealer Plus BC [SP] and Bio C Sealer [BCS]). Bond strength and failure mode were evaluated according to the sealer, drying protocol, and root canal third. Sixty extracted human mandibular single-rooted premolars were selected after anatomical standardization. The crowns were sectioned and root canals were prepared. Roots were randomly divided into four groups (n = 15 each). Each group was assigned a combination of one of the evaluated sealers (SP or BCS) and one of the drying protocols: canals dried with paper points (PP) or irrigation with saline followed by aspiration with silicon cannulas (IA). Obturations were performed using a single-cone technique. The teeth were temporized and stored for 7 days (100% humidity, 37°C). Roots were cut to obtain 2 mm thick discs for each third (coronal, middle, and apical). Push-out tests were performed on a universal testing machine, and the bond strength (MPa) of each specimen was calculated by dividing the load (N) by the interface area. Failure type was assessed under ×4 magnification. Data were statistically analyzed with a significance set at 5%. An analysis of variance test followed by the Games-Howell post-hoc test was used to compare the mean values between the groups and the interaction of the variables. The predominant failure type was cohesive, followed by mixed failure and adhesive in all groups. The apical third presented the highest bond strength (p < 0.05) regardless of the group, followed by the middle and coronal thirds. Overall, the SP PP group had the highest mean bond strength (p < 0.01), but the SP sealer was negatively affected by the IA drying protocol in the coronal and middle thirds. The BCS presented similar results within the third stage, regardless of the drying protocol. Sealer Plus BC had a higher bond strength than Bio C Sealer, but it was negatively affected by the irrigation-aspiration protocol in the coronal and middle thirds. For the apical third, there was no difference between the groups; thus, a similar bond strength was observed regardless of the drying protocol or sealer.


Transcriptome profiles of carcinoma-in-situ and invasive non-small cell lung cancer as revealed by SAGE.
Non-small cell lung cancer (NSCLC) presents as a progressive disease spanning precancerous, preinvasive, locally invasive, and metastatic lesions. Identification of biological pathways reflective of these progressive stages, and aberrantly expressed genes associated with these pathways, would conceivably enhance therapeutic approaches to this devastating disease. Through the construction and analysis of SAGE libraries, we have determined transcriptome profiles for preinvasive carcinoma-in-situ (CIS) and invasive squamous cell carcinoma (SCC) of the lung, and compared these with expression profiles generated from both bronchial epithelium, and precancerous metaplastic and dysplastic lesions using Ingenuity Pathway Analysis. Expression of genes associated with epidermal development, and loss of expression of genes associated with mucociliary biology, are predominant features of CIS, largely shared with precancerous lesions. Additionally, expression of genes associated with xenobiotic metabolism/detoxification is a notable feature of CIS, and is largely maintained in invasive cancer. Genes related to tissue fibrosis and acute phase immune response are characteristic of the invasive SCC phenotype. Moreover, the data presented here suggests that tissue remodeling/fibrosis is initiated at the early stages of CIS. Additionally, this study indicates that alteration in copy-number status represents a plausible mechanism for differential gene expression in CIS and invasive SCC. This study is the first report of large-scale expression profiling of CIS of the lung. Unbiased expression profiling of these preinvasive and invasive lesions provides a platform for further investigations into the molecular genetic events relevant to early stages of squamous NSCLC development. Additionally, up-regulated genes detected at extreme differences between CIS and invasive cancer may have potential to serve as biomarkers for early detection.


Pauling-Type Adsorption of O2 Induced by Heteroatom Doped ZnIn2S4 for Boosted Solar-Driven H2O2 Production.
Breaking the trade-off between activity and selectivity has perennially been a formidable endeavor in the field of hydrogen peroxide (H2O2) photosynthesis, especially the side-on configuration of oxygen (O2) on the catalyst surface will cause the cleavage of O-O bonds, which drastically hinders the H2O2 production performance. Herein, we present an atomically heteroatom P doped ZnIn2S4 catalyst with tunable oxygen adsorption configuration to accelerate the ORR kinetics essential for solar-driven H2O2 production. Indeed, the spectroscopy characterizations (such as EXAFS and in situ FTIR) and DFT calculations reveal that heteroatom P doped ZnIn2S4 at substitutional and interstitial sites, which not only optimizes the coordination environment of Zn active sites, but also facilitates electron transfer to the Zn sites and improves charge density, avoiding the breakage of O-O bonds and reducing the energy barriers to H2O2 production. As a result, the oxygen adsorption configuration is regulated from side-on (Yeager-type) to end-on (Pauling-type), resulting in the accelerated ORR kinetics from 874.94 to 2107.66 μmol g-1 h-1. This finding offers a new avenue toward strategic tailoring oxygen adsorption configuration by the rational design of doped photocatalyst.


[Congenital adrenal hyperplasia: a qualitative study on sex definition and redesignation dilation surgery and psychological support (part II)].
To identify relevant questions related to sex definition and re-designation and reconstructive surgery in patients with congenital adrenal hyperplasia (CAH), and to understand the role of the psychologist in providing care for these patients. We selected 21 subjects: 7 pediatric endocrinologists from 5 Brazilian Public Health System institutions, 9 parents and 6 patients with CAH, according to a qualitative research model. In this paper, 3 of the studied categories are analyzed: 'sex definition and re-designation', 'reconstructive surgery/vaginal dilation', and 'psychology'. Parents' main anguish relates to the situation of an unnamed sex at birth, whereas sex re-designation was distressful to physicians. A sense of loneliness when dealing with the disease and treatment was a common anguish among patients; dilation procedures were the major complaint. In general, physicians recommend that genital reconstructive surgery be performed early on to avoid future trauma. In such a complex scenario, it is remarkable that not all the reference service staff have a psychologist on duty. Difficulties to deal with questions involving sexuality were evident and dilation procedures are an additional source of trauma for these patients.


Stereotactic body radiation therapy for early non-small cell lung cancer.
For patients with early stage non-small cell lung cancer (NSCLC) unsuitable for resection local high-dose radiotherapy is the treatment of choice. In modern series even with escalated conformal radiotherapy local control rates of about 55% remain disappointing. Within the last years, stereotactic radiotherapy has been shown an effective treatment approach for early stage malignant lung tumors, combining the accurate focal dose delivery by stereotactic techniques with the biological advantages of dose escalated hypofractionated radiotherapy. Typical treatment regimens include three to five fractions over 1-2 weeks or 1 single fraction as radiosurgery. With adequate staging procedures including FDG-PET-CT scan and a low probability of subclinical involvement of unsuspicious locoregional lymph nodes, the concept is to irradiate the primary T1/2 tumor alone. Recent data report local control rates of up to 90%, with favorable results especially for patients in good general condition. Less than 10% of all patients develop isolated tumor recurrences in regional lymph nodes. Three-year survival is significantly improved to more than 80% when biological effective doses of more than 100 Gy are applied to patients in good conditions. Systemic tumor recurrence still is a major problem, making an additional systemic chemotherapy interesting for selected patients after hSRT, such as those younger than 75 years.


Thresholds of hypoxia for marine biodiversity.
Hypoxia is a mounting problem affecting the world's coastal waters, with severe consequences for marine life, including death and catastrophic changes. Hypoxia is forecast to increase owing to the combined effects of the continued spread of coastal eutrophication and global warming. A broad comparative analysis across a range of contrasting marine benthic organisms showed that hypoxia thresholds vary greatly across marine benthic organisms and that the conventional definition of 2 mg O(2)/liter to designate waters as hypoxic is below the empirical sublethal and lethal O(2) thresholds for half of the species tested. These results imply that the number and area of coastal ecosystems affected by hypoxia and the future extent of hypoxia impacts on marine life have been generally underestimated.


[Consequences of resecting the ileocecal union].
22 patients, divided in 2 groups, are studied under-going intestinal resection as consequence of different pathological entities. Group I of 13 patients who had the ileocecal unión resected. Group II is made up of 9 patients who had small fragments of the small intestine enucleated. All the patients have, among other things, various anthropometrical, hematological and biochemical parameters, and their Ca/P metabolism analyzed, as well as the elimination of urinary nitrogen in its different forms. The patients who underwent resection of the ileocecal union present anthropometrical alterations, which can be consequence of a state of chronic malnutrition. The differences found in the alkaline phosphatase and in the elimination of amino acids in the urine can be a sign of a bacterial contamination of the small intestine by fecal flora or a sign of less availability of energetic contribution.


Primary Family Caregivers' Reasons for Disclosing Versus Not Disclosing a Cancer Diagnosis in India.
Nondisclosure of cancer diagnosis continues to be practiced in India, with many family caregivers concealing it from patients in order to protect them from emotional distress. The aim of this study was to explore Indian primary family caregivers' reasons for, and experiences of, disclosure versus nondisclosure to patients about their cancer diagnosis. Indian disclosing (n = 8) and nondisclosing (n = 7) primary family caregivers participated in semistructured interviews exploring their reasons for disclosure versus nondisclosure of cancer diagnosis to their patient. Qualitative content analysis was used to classify the reasons for and for not disclosing. Illustrative quotes were selected to highlight caregivers' motivations for, and experiences of, each reason. The findings revealed 6 main reasons for disclosing (emotional well-being, lack of control, preparing the patient, family reasons, patient's personality, and longevity/curability of the disease) and 6 reasons for not disclosing (emotional well-being, family reasons, patient's personality, longevity/curability of the disease, barriers to communication, and disease severity). Typically, disclosing caregivers considered reasons for as well as against disclosure, whereas nondisclosing caregivers considered reasons against disclosure. Most of the reasons given for disclosing and not disclosing were the same, although these reasons operated differently for disclosing and nondisclosing caregivers. In addition, justification for these reasons demonstrated cognitive consistency effects that appeared to reduce any feelings of dissonance regarding caregivers' disclosure, or nondisclosure, decisions. Cancer nurses should provide additional psychological support to nondisclosing caregivers, especially with regard to how they view and engage in their caregiving role.


Critical roles for multiple formins during cardiac myofibril development and repair.
Cardiac and skeletal muscle function depends on the proper formation of myofibrils, which are tandem arrays of highly organized actomyosin contractile units called sarcomeres. How the architecture of these colossal molecular assemblages is established during development and maintained over the lifetime of an animal is poorly understood. We investigate the potential roles in myofibril formation and repair of formin proteins, which are encoded by 15 different genes in mammals. Using quantitative real-time PCR analysis, we find that 13 formins are differentially expressed in mouse hearts during postnatal development. Seven formins immunolocalize to sarcomeres in diverse patterns, suggesting that they have a variety of functional roles. Using RNA interference silencing, we find that the formins mDia2, DAAM1, FMNL1, and FMNL2 are required nonredundantly for myofibrillogenesis. Knockdown phenotypes include global loss of myofibril organization and defective sarcomeric ultrastructure. Finally, our analysis reveals an unanticipated requirement specifically for FMNL1 and FMNL2 in the repair of damaged myofibrils. Together our data reveal an unexpectedly large number of formins, with diverse localization patterns and nonredundant roles, functioning in myofibril development and maintenance, and provide the first evidence of actin assembly factors being required to repair myofibrils.


[The principles and late results of the surgical treatment of chronic subdural hematoma in nursing infants].
Principles of surgical treatment of 68 infants with chronic subdural hematoma are substantiated. Late follow-up results analysis has shown that the application of all of the modern neurosurgical diagnostic methods permits to choose correctly the method of treatment and to prognosticate its result. Result of treatment was not influenced substantially by the hematoma evacuation procedure performance, in 37 patients good result occurred. Poor result of patient's treatment is due to the concomitant or caused by hematoma brain affection.


Localization of type-specific epitopes of herpes simplex virus type 2 glycoprotein G recognized by human and mouse antibodies.
Glycoprotein G is a major target for the humoral immune response against herpes simplex virus (HSV) and a prototype antigen for type-specific serodiagnosis discriminating HSV-1 and HSV-2 infections. The mature part of HSV-2 glycoprotein G-2 (gG-2) contains a unique stretch suspected to mediate type specificity, and in addition a region homologous to HSV-1 glycoprotein G-1 (gG-1). Antigenic determinants of the mature gG-2 were mapped by testing the reactivity of mouse anti-gG-2 monoclonal antibodies (MAbs) and purified human anti-gG-2 antibodies with synthetic peptides coupled to cellulose membranes. The anti-gG-2 MAbs bound to four epitopes localized in a narrow cluster within a gG-2 segment delimited by amino acids (aa) 552 and 611. This cluster was located between the predicted O-glycan-rich region and the transmembrane anchor sequence. The epitopes of the human anti-gG-2 antibodies were localized within three stretches of amino acids, two of which were overlapping with those recognized by anti-gG-2 MAbs. One of these stretches, delimited by aa 552 and 574, showed reactivity to all human HSV-2 sera tested, but not to HSV-1 sera or to purified anti-gG-1 antibodies. Neither the anti-gG-2 MAbs nor the purified human anti-gG-2 antibodies were cross-reactive to gG-1 peptides or HSV-1 antigen, although most of the epitopes were localized within the part of gG-2 which was homologous to gG-1. The findings concerning HSV-2 type-specific human antibody response to a defined stretch within gG-2 may be of importance for the further development of type-discriminating serodiagnosis.


Osteoconductive Amine-Functionalized Graphene-Poly(methyl methacrylate) Bone Cement Composite with Controlled Exothermic Polymerization.
Bone cement has found extensive usage in joint arthroplasty over the last 50 years; still, the development of bone cement with essential properties such as high fatigue resistance, lower exothermic temperature, and bioactivity has been an unsolved problem. In our present work, we have addressed all of the mentioned shortcomings of bone cement by reinforcing it with graphene (GR), graphene oxide (GO), and surface-modified amino graphene (AG) fillers. These nanocomposites have shown hypsochromic shifts, suggesting strong interactions between the filler material and the polymer matrix. AG-based nanohybrids have shown greater osteointegration and lower cytotoxicity compared to other nanohybrids as well as pristine bone cement. They have also reduced oxidative stress on cells, resulting in calcification within 20 days of the implantation of nanohybrids into the rabbits. They have significantly reduced the exothermic curing temperature to body temperature and increased the setting time to facilitate practitioners, suggesting that reaction temperature and settling time can be dynamically controlled by varying the concentration of the filler. Thermal stability and enhanced mechanical properties have been achieved in nanohybrids vis-à-vis pure bone cement. Thus, this newly developed nanocomposite can create natural bonding with bone tissues for improved bioactivity, longer sustainability, and better strength in the prosthesis.


Comprehensive characterization of atmospheric organic matter in Fresno, California fog water.
Fogwater collected during winter in Fresno (CA) was characterized by isolating several distinct fractions and characterizing them by infrared and nuclear magnetic resonance (NMR) spectroscopy. More than 80% of the organic matter in the fogwater was recovered and characterized. The most abundant isolated fractions were those comprised of volatile acids (24% of isolated carbon) and hydrophilic acids plus neutrals (28%). Volatile acids, including formic and acetic acid, have been previously identified as among the most abundant individual species in fogwater. Recovered hydrophobic acids exhibited some properties similar to aquatic fulvic acids. An insoluble particulate organic matter fraction contained a substantial amount of biological material, while hydrophilic and transphilic fractions also contained material suggestive of biotic origin. Together, these fractions illustrate the important contribution biological sources make to organic matter in atmospheric fog droplets. The fogwater also was notable for containing a large amount of organic nitrogen present in a variety of species, including amines, nitrate esters, peptides, and nitroso compounds.


Determination of protein-ligand interactions using differential scanning fluorimetry.
A wide range of methods are currently available for determining the dissociation constant between a protein and interacting small molecules. However, most of these require access to specialist equipment, and often require a degree of expertise to effectively establish reliable experiments and analyze data. Differential scanning fluorimetry (DSF) is being increasingly used as a robust method for initial screening of proteins for interacting small molecules, either for identifying physiological partners or for hit discovery. This technique has the advantage that it requires only a PCR machine suitable for quantitative PCR, and so suitable instrumentation is available in most institutions; an excellent range of protocols are already available; and there are strong precedents in the literature for multiple uses of the method. Past work has proposed several means of calculating dissociation constants from DSF data, but these are mathematically demanding. Here, we demonstrate a method for estimating dissociation constants from a moderate amount of DSF experimental data. These data can typically be collected and analyzed within a single day. We demonstrate how different models can be used to fit data collected from simple binding events, and where cooperative binding or independent binding sites are present. Finally, we present an example of data analysis in a case where standard models do not apply. These methods are illustrated with data collected on commercially available control proteins, and two proteins from our research program. Overall, our method provides a straightforward way for researchers to rapidly gain further insight into protein-ligand interactions using DSF.


Structure and composition of rat precorneal tear film. A study by an in vivo cryofixation.
To visualize the in vivo structure and to investigate the composition of rat precorneal tear film. An in vivo cryofixation with freeze substitution method of electron microscopy was used for the study. For light and transmission electron microscopy, a small amount of aluminum powder was used as a tracer spread on the corneal surface. The eyeballs were immediately and quickly frozen by pouring an isopentane-propane mixture cooled by liquid nitrogen directly over the eyes. For scanning electron microscopy, the corneal surface was freeze-fractured after the cryofixation. The specimens were then freeze-substituted and prepared conventionally for microscopic observation. The tear film appeared as a layer of homogeneous and fine network-like structures varying from 2 to 6 microns in thickness on the corneal surface, with a membrane-like layer covering its surface. The aluminum powder was located on the surface of the tear film. The tear film could be removed completely by applying 10% or 20% acetylcysteine, but not by phosphate buffer. The in vivo structure of the rat tear film is composed primarily of mucus, with a lipid layer covering its surface but without a free aqueous layer. The "three layers theory" of tear film structure requires revisions.


Vanadyl complexes with dansyl-labelled di-picolinic acid ligands: synthesis, phosphatase inhibition activity and cellular uptake studies.
Vanadium complexes have been previously utilised as potent inhibitors of cysteine based phosphatases (CBPs). Herein, we present the synthesis and characterisation of two new fluorescently labelled vanadyl complexes (14 and 15) with bridged di-picolinic acid ligands. These compounds differ significantly from previous vanadyl complexes with phosphatase inhibition properties in that the metal-chelating part is a single tetradentate unit, which should afford greater stability and scope for synthetic elaboration than the earlier complexes. These new complexes inhibit a selection of cysteine based phosphatases (CBPs) in the nM range with some selectivity. Fluorescence spectroscopic studies (including fluorescence anisotropy) were carried out to demonstrate that the complexes are not simply acting as vanadyl delivery vehicles but they interact with the proteins. Finally, we present preliminary fluorescence microscopy studies to demonstrate that the complexes are cell permeable and localise throughout the cytoplasm of NIH3T3 cells.


Sealing ability of three fiber dowel systems.
To study the sealing ability of two new fiber dowel systems. Thirty-six extracted single-rooted teeth were endodontically treated and randomly assigned to two new fiber dowel systems and a control group: (1) an E-glass-based dowel, everStick-POST, cemented with ParaCem Universal DC resin cement (EV); (2) a glass-fiber dowel, RelyX Fiber Post, cemented with RelyX Unicem self-adhesive resin cement (RX). The control group was restored with a glass-fiber dowel, ParaPost Fiber Lux, cemented with ParaCem Universal DC resin cement (PP). The roots were isolated and immersed in a 50 wt% ammoniacal silver nitrate solution for 24 hours followed by 8 hours in a photo-developing solution. The roots were sectioned in 1-mm-thick disks perpendicular to the long axis of the root. The specimens were processed for backscattered FESEM observation. For each tooth, the depth of silver infiltration into the root canal was measured by ranks from 0 to 8. For each disk, silver infiltration was measured as the percentage of leakage around the adhesive interface. Data were analyzed with Kruskal-Wallis nonparametric tests at a significance level of 95%. When the silver infiltration was computed from the coronal to the apical aspects of the root, RX resulted in the lowest degree of silver infiltration, but not statistically different from that of EV (p < 0.148). RX, however, resulted in a lower depth of silver infiltration than the control group PP at p < 0.023. EV resulted in a statistically similar depth of penetration to PP (p= 0.492). Although the total mean percentage of silver infiltration at the dentin-resin cement interface was statistically similar for all groups (p= 0.632), EV resulted in the greater number of disks with silver infiltration (23 out of 96), followed by PP (21 out of 96) and RX (14 out of 96). None of the specimens showed leakage around the dowel-resin cement interface. The use of the E-glass dowels in EV did not improve the root-wall sealing ability compared with the control group PP. The system RX, which uses a new simplified self-adhesive protocol, resulted in a lower depth of silver infiltration than the control group PP.


Recurrent hepatitis B in liver allograft recipients. Differentiation between viral hepatitis B and rejection.
The histologic findings in the original liver obtained from 9 liver allograft patients with active B virus hepatitis were compared with 28 posttransplant pathology specimens. All specimens were studied with the use of light and immunohistochemical microscopy in conjunction with pertinent clinical data. Eight of the 9 patients had chronic active hepatitis B (HB) with cirrhosis, prior to transplant, one of which had coexistent hepatocellular carcinoma. The ninth patient had fulminant hepatic necrosis secondary to acute HB prior to transplantation. In all of the patients with chronic HB prior to transplantation who survived more than 2 months after transplantation recurrent infection of the graft developed despite perioperative HB immunoglobulin therapy. The patient with acute fulminant hepatitis B pretransplant has done well postoperatively and has evidence of HB virus immunity (positive anti-HBs) 15 months after transplantation. Examination of tissue specimens obtained during episodes of allograft dysfunction in these 9 patients indicate that pathologic alterations of active HB infection of the allograft are associated with a preferential lobular insult, whereas those occurring in rejection preferentially involve portal tract structures. Serologic data combined with biopsy histopathologic data are essential in distinguishing between the two quite different events.


[Transcatheter closure of atrial septal defects in the oval fossa].
We report five years' experience with transcatheter closure of defects in the oval fossa at Rikshospitalet University Hospital in Oslo, Norway. We reviewed the results in 69 patients between 1.3 and 74 years of age (median 5.3), weighing median 20 kg (7.8-109), with pulmonary blood flow 2.40.74 (1.3-4.8) times systemic flow, and median diameter of the defect 18 mm (9-34). The patients were followed clinically for one year. In 69/77 (90%) the defect could be closed. None had a significant residual shunt. One patient showed a very small residual leak after one year. Two children, not yet seen after one year, had a small shunt after one month. The complication rate has been low, and we have not been able to demonstrate any sequelae. The hospital stay is two nights without any convalescence period. The results compare favourably to surgery. The method was efficient and safe in all age and weight groups. The very limited total volume of such procedures indicates they should be centralised and only carried out by a small number of physicians.


IL-17A promotes protective IgA responses and expression of other potential effectors against the lumen-dwelling enteric parasite Giardia.
Giardia lamblia is a leading protozoan cause of diarrheal disease worldwide. It colonizes the lumen and epithelial surface of the small intestine, but does not invade the mucosa. Acute infection causes only minimal mucosal inflammation. Effective immune defenses exist, yet their identity and mechanisms remain incompletely understood. Interleukin (IL)-17A has emerged as an important cytokine involved in inflammation and antimicrobial defense against bacterial pathogens at mucosal surfaces. In this study, we demonstrate that IL-17A has a crucial function in host defense against Giardia infection. Using murine infection models with G. muris and G. lamblia, we observed marked and selective induction of intestinal IL-17A with peak expression after 2 weeks. Th17 cells in the lamina propria and innate immune cells in the epithelial compartment of the small intestine were responsible for the IL-17A response. Experiments in gene-targeted mice revealed that the cytokine, and its cognate receptor IL-17RA, were required for eradication of the parasite. The actions of the cytokine were mediated by hematopoietic cells, and were required for the transport of IgA into the intestinal lumen, since IL-17A deficiency led to marked reduction of fecal IgA levels, as well as for increased intestinal expression of several other potential effectors, including β-defensin 1 and resistin-like molecule β. In contrast, intestinal hypermotility, another major antigiardial defense mechanism, was not impacted by IL-17A loss. Taken together, these findings demonstrate that IL-17A and IL-17 receptor signaling are essential for intestinal defense against the important lumen-dwelling intestinal parasite Giardia.


Epidemiology and Clinical Outcomes of Patients With Inflammatory Bowel Disease Presenting With Acute Coronary Syndrome.
Inflammatory bowel disease (IBD) is associated with an increased acute coronary syndrome (ACS) risk. Data are limited regarding the epidemiology and outcomes of ACS in patients with IBD. A retrospective cohort analysis of patients with IBD admitted for ACS in the U.S. Healthcare Cost and Utilization Project National Inpatient Sample for 2005 to 2015 was conducted. We analyzed trends in IBD-ACS admissions and mortality, differences in risk profiles, management strategies, and in-hospital mortality between IBD-ACS and non-IBD ACS and between ulcerative colitis (UC) and Crohn disease (CD). We studied 6,872,415 non-IBD ACS and 24,220 IBD-ACS hospitalizations (53% with CD). During the study period, the number of hospitalizations for IBD-ACS increased, particularly those related to CD. Compared with non-IBD ACS, patients with IBD-ACS had a lower prevalence of cardiovascular risk factors and similar rates of coronary angiography and revascularization. The in-hospital mortality rate was lower with IBD-ACS (3.9%) compared with non-IBD ACS (5.3%; odds ratio, 0.81; 95% confidence interval, 0.69-0.96; P = 0.011) and was stable between 2005 and 2015. Risk factors, ACS management strategies, and mortality were similar between CD and UC. Coagulopathy, weight loss, and gastrointestinal bleeding were more frequent in IBD-ACS and were strong independent predictors of mortality. Hospitalizations for ACS in patients with IBD increased in recent years but death rates were stable. The ACS-related risk profiles and mortality were modestly favorable with IBD-ACS than with non-IBD ACS and were similar between CD and UC. Complications more frequently associated with IBD were strongly associated with mortality. These findings indicate that aggressive management of IBD and ACS comorbidities is required to improve outcomes.


[Prognostic value of the androgenic function state of patients with lung cancer].
The authors have studied interconnection between daily excretion of androgenous metabolites and life-span of patients with lung cancer of different histological gradation. Positive correlation was found between life-span of patients with lung cancer and index of androsterone daily excretion. The patients with lung cancer of high differentiation had their androgenous fractions daily excretion compared with those of healthy persons, and patients with the lung cancer of middle and low degree of differentiation had their androgenous fractions daily excretion considerably lower than those of healthy persons.


New 1-hydroxy-2-thiopyridine derivatives active against both replicating and dormant Mycobacterium tuberculosis.
Tuberculosis (TB) treatment is confounded by the range of metabolic states displayed by Mycobacterium tuberculosis, by the long duration required and by the increasing prevalence of drug-resistant strains. Latent TB infection is especially difficult to treat due to the phenotypic antibiotic resistance of non-replicating M. tuberculosis. Therefore, the development of new drugs effective against both active and latent TB infection is needed. New 1-hydroxy-2-thiopyridine derivatives were synthesized and found to be highly effective in vitro against both actively growing and dormant non-culturable M. tuberculosis. Such compounds are leads for the development of new drugs for all forms of TB including latent infection.


A prospective controlled trial of early postoperative oral intake following major abdominal gynecologic surgery.
The objective was to determine whether, when compared with traditional dietary advancement, early oral intake following major gynecologic surgery leads to a reduction in the length of hospitalization. Patients undergoing major abdominal gynecologic surgery were invited to participate in this study. After informed consent was obtained, they were randomized to one of two groups. The control group (group 1) was treated traditionally. Oral intake was initiated only after documentation of bowel function, which was defined by two of the following three criteria: (1) bowel sounds; (2) flatus or bowel movement; and (3) subjective hunger. Those assigned to the study group (group 2) were given a clear liquid diet on postoperative day 1. Once 500 cc was tolerated, a regular diet was given. Patients were evaluated on a daily basis for bowel sounds, flatus, bowel movement, hunger, nausea, vomiting, and need for nasogastric tube decompression. The groups were compared with regard to length of hospital stay, length of postoperative ileus, and incidence of adverse effects including nausea, vomiting, and postoperative complications. Statistical analyses were performed with the Student t and chi 2 tests. The demographic characteristics of the control (N = 47) and study groups (N = 49) were similar, with no significant differences in underlying medical conditions, prior abdominal surgery, or diagnosis of a malignancy. The groups did not vary statistically in the number of subjects who required postoperative antiemetics or postoperative biscodyl suppository. There was a statistically significant reduction in the length of hospitalization for those patients on the early feeding regimen. The average length of stay for group 1 was 4.02 days +/- 0.30 (SEM), while that for group 2 was 3.12 days +/- 0.16 (P = 0.008). While there was a significantly higher incidence of emesis in the study population, this was not associated with any untoward outcome, and this group actually tolerated a solid diet nearly one full day earlier (2.72 days +/- 0.14 vs 1.88 days +/- 0.14, P < 0.0001). Early postoperative oral intake results in a decreased length of hospitalization and is well tolerated when compared with traditional dietary management in patients undergoing abdominal surgery on a university gynecologic oncology service.


Augmentation by chlorpropamide of 1-deamino-8-D-arginine vasopressin-induced antidiuresis and stimulation of renal medullary adenylate cyclase and accumulation of adenosine 3',5'-monophosphate.
The effect of chlorpropamide was determined in Brattleboro diabetes insipidus (DI) rats that were injected with 1-deamino-8-D-arginine vasopressin (dDAVP). Chlorpropamide augmented the antidiuretic responses to 0.78 and 1.56 ng dDAVP but not to larger doses. In an effort to explain this observation we investigated the effect of chlorpropamide on renal medullary adenylate cyclase activation by dDAVP and on phosphodiesterase activity. We found that the injection of chlorpropamide increased adenylate cyclase activation by dDAVP added in vitro to renal medullary cell membrane preparations from Brattleboro DI rats but had no effect on phosphodiesterase activity. When kidneys from Brattleboro DI rats, treated and not treated with chlorpropamide, were perfused in vitro, we found that 10(-4) M dDAVP increased the concentration of cAMP in comparison to untreated and chlorpropamide-treated groups, and that chlorpropamide plus dDAVP resulted in a greater concentration of renal cAMP than was found with dDAVP alone. We believe that treatment with chlorpropamide increases dDAVP-stimulated renal medullary adenylate cyclase activity without altering phosphodiesterase activity and that this leads to increased renal cAMP concentrations. This, in turn, causes an augmented antidiuresis in response to dDAVP.


Connected health care: the future of health care and the role of the pharmacist.
The population of the world is ageing. As a result, the incidence of chronic disease is projected to increase, there are predicted shortages in health care workforce and budget restraints; implications for future health care provision are serious. The current model of health care is not equipped to deal with these changes. Connected health care, via the use of health informatics, disease management and home telehealth technologies, has been suggested as an approach to ease the projected strain on future health care. Evidence to date suggests a positive impact of the use of connected health care model; however, the majority of studies have overlooked the involvement of the community pharmacist. As the most common point of contact with primary health services for most of the population, the community pharmacist may be well placed to provide connected health care. The research to date is promising with improvements in outcomes for cardiovascular patients noted; however, further work is required to investigate the potential role the community pharmacist can play in the future of connected health care.


Magnetic resonance imaging assessment of squamous cell carcinoma of the anal canal before and after chemoradiation: can MRI predict for eventual clinical outcome?
To describe the MRI appearances of squamous cell carcinoma of the anal canal before and after chemoradiation and to assess whether MRI features predict for clinical outcome. Thirty-five patients (15 male, 20 female; mean age 60.8 years) with histologically proven squamous cell cancer of the anal canal underwent MRI before and 6-8 weeks after definitive chemoradiation. Images were reviewed retrospectively by two radiologists in consensus blinded to clinical outcome: tumor size, signal intensity, extent, and TNM stage were recorded. Following treatment, patients were defined as responders by T and N downstaging and Response Evaluation Criteria in Solid Tumors (RECIST). Final clinical outcome was determined by imaging and case note review: patients were divided into (1) disease-free and (2) with relapse and compared using appropriate univariate methods to identify imaging predictors; statistical significance was at 5%. The majority of tumors were ≤T2 (23/35; 65.7%) and N0 (21/35; 60%), mean size 3.75 cm, and hyperintense (++ to +++, 24/35 patients; 68%). Following chemoradiation, there was a size reduction in all cases (mean 73.3%) and a reduction in signal intensity in 26/35 patients (74.2%). The majority of patients were classified as responders (26/35 (74.2%) patients by T and N downstaging; and 30/35 (85.7%) patients by RECIST). At a median follow-up of 33.5 months, 25 patients (71.4%) remained disease-free; 10 patients (28.6%) had locoregional or metastatic disease. Univariate analysis showed that no individual MRI features were predictive of eventual outcome. Early assessment of response by MRI at 6-8 weeks is unhelpful in predicting future clinical outcome.