Practical Machine Learning Model to Predict the Recovery of Motor Function in Patients with Stroke.
Machine learning (ML) is an artificial intelligence technique in which a system learns patterns and rules from a given data. The objective of the study was to investigate the potential of ML for predicting motor recovery in stroke patients. We analyzed data from 833 consecutive stroke patients using 3 ML algorithms: deep neural network (DNN), random forest, and logistic regression. We created a practical ML model using the most common data measured in almost all rehabilitation hospitals as input data. Demographic and clinical data, including modified Brunnstrom classification (MBC) and functional ambulation classification (FAC), were collected when patients were transferred to the rehabilitation unit (8-30 days) and 6 months after stroke onset and were used as input data. Motor outcomes at 6 months after stroke onset of the affected upper and lower extremities were classified according to MBC and FAC, respectively. Patients with an MBC of <5 and an FAC of <4 at 6 months after stroke onset were considered to have a "poor" outcome, whereas those with MBC ≥5 and FAC ≥4 were considered to have a "good" outcome. The area under the curve (AUC) for the DNN model for predicting motor function was 0.836 for the upper and lower limb motor functions. For the random forest and logistic regression models, the AUCs were 0.736 and 0.790 for the upper and lower limb motor functions, respectively. The AUCs for the random forest and logistic regression models were 0.741 and 0.795 for the upper and lower limb motor functions, respectively. Although we used simple and common data that can be obtained in clinical practice as variables, our DNN algorithm was useful for predicting motor recovery of the upper and lower extremities in stroke patients during the recovery phase.


Some characteristics of voice in near-total laryngectomy.
Some vocal characteristics were compared in two groups of examinees: patients after near-total laryngectomy and a control group of healthy examinees. Acoustic analysis was carried out using Multi Dimensional Voice Program and Spectra LAB program. Analyzed parameters were: fundamental frequency, the range of fundamental frequency, maximum phonation time, jitter, shimmer, noise to harmonic ratio, voice turbulence index, degree of voice breaks and intensity of voice. We found that voice after near-total laryngectomy had normal mean fundamental frequency, larger range of fundamental frequency, jitter and shimmer were high, as were noise to harmonic ratio and voice turbulence index. Maximum phonation time was short and intensity was lower compared to control group. Degree of voice breaks was significant in near-total laryngectomy group.


Chartarlactams A-P, phenylspirodrimanes from the sponge-associated fungus Stachybotrys chartarum with antihyperlipidemic activities.
Chemical examination of the solid culture of the endophytic fungus Stachybotrys chartarum isolated from the sponge Niphates recondita resulted in the isolation of 16 new phenylspirodrimanes, named chartarlactams A-P (1-16), together with eight known analogues. Their structures were determined on the basis of extensive spectroscopic analysis, including X-ray single-crystal diffraction for the determination of the absolute configurations. The isoindolone-drimane dimer chartarlactam L (12) was determined as a new skeleton. Compounds 1-6 and 8-24 were evaluated for antihyperlipidemic effects in HepG2 cells, and the primary structure-activity relationships are discussed.


Role and molecular mechanism of stem cells in colorectal cancer initiation.
In recent years, the rate of colorectal cancer has sharply increased, especially in China, where it ranks second for the number of cancer fatalities. Currently, the treatment of colorectal cancer patients involves the combination of resection surgery and treatment with postoperative anticancer drugs such as 5-FU and oxaliplatin. However, recurrence and metastasis after treatment are still the dominant reasons for the low survival rate. Colorectal cancer stem cells (CSCs) are regarded as the key contributors to tumour recurrence and metastasis due to their resistance to chemotherapy drugs and their extremely high tumourigenicity. Once CSCs overcome chemotherapy treatment, they continue to survive and reinitiate proliferation to form tumours, leading to recurrence. The dominant reason for CSC resistance is that most anticancer drugs are aimed at inhibiting proliferative pathways in cancer cells that differ from those in CSCs. Therefore, studies on the characteristics of CSCs and their intracellular molecular pathways are essential for the exploration of CSC-targeted drugs. In this report, we review recent advances in the research of CSCs and, in particular, review the important intracellular molecular pathways, such as HOXA5-catenin, STRAP-NOTCH and YAP/TAZ, related to the maintenance and differentiation of stem cells to generate a theoretical basis for the exploration of CSC-targeted drugs.


Similar serum IgM concentrations in Greek endemic goiter and control populations: failure to confirm previous experience.
Circulating immunoglobulin M (IgM) concentrations were determined in 47 nontoxic goiter patients from four Greek endemic goiter areas, and in 13 patients from Athens, a non-goitrous area; and compared with 38 control non-goitrous subjects from the same goiter regions, and 23 more controls from Athens. The values in both goitrous and non-goitrous groups were indistinguishable. Current techniques for single radial immunodiffusion were employed. The results are expressed in standardized international units/ml serum, instead of the formerly used mg/dl. The present findings are in disagreement with the earlier observation from this laboratory that 40 per cent of goitrous patients had elevated IgM values compared with 10 per cent of control subjects.


Formation of copper nanowires by electroless deposition using microtubules as templates.
Microtubules (MTs) are self-assembling, protein-based, tubular structures several micrometers long with outer and inner diameters of 25 nm and 15 nm, respectively. This aspect ratio makes MTs ideal templates for producing nanowires for applications such as electrical nano-interconnects. MTs are poorly conductive and their use as interconnects necessitates their metallization. We report a process for metallization of MTs with copper using a biologically benign electroless deposition chemistry consisting of copper sulfate solution containing acetic acid as a complexant and ascorbic acid as reducing agent. The pH of the plating bath is controlled such that copper metallization occurs without disassembling the MTs. Electron microscopic characterization of the morphology and dimensions of the copper nanowires shows that metallization for approximately 1 minute produces a uniform nanowire with an average diameter of approximately 15 nm, suggesting that metallization is initiated selectively from the MT inner core.


Can Cheiromancy Predict Mean Survival or Fatality of a Patient with Amyotrophic Lateral Sclerosis?
Background The past three decades have seen palmistry as an interface to human health. There have been no previously organized attempts in utilizing this knowledge to predict the state of disease. Objective Due to unavailability of any biological marker for diagnosing amyotrophic lateral sclerosis (ALS) till date, we attempt to examine whether palmistry could be used for detecting the onset and survival of patient suffering from ALS. Methods Patients suffering from ALS attending the neurology outpatient department at Postgraduate Institute of Medical Education and Research, India were selected for study. Palm photographs were obtained from all patients including controls after their consent. Patients suffering from other comorbidities such as diabetes, hypertension, migraine, as well as smokers and nonsmokers were included in the study. Twenty-six ALS patients, 30 neurological controls, and 34 healthy age matched controls were recruited in the study. Retrospective analysis of the palm pictures based on blinding method was performed by academically qualified palmists. Results The results demonstrated the need for further studies in the subject even though the observations made were independent by both the palmists. Conclusion This study opens new vistas for cheiromancy to be further explored for analysis in larger samples.


Surgical options for patients with Lennox-Gastaut syndrome.
Despite ongoing investigation into pharmacologic treatments for Lennox-Gastaut syndrome (LGS), outcomes for chronic administration of medications remain disappointing. In many instances LGS is treatment refractory, resulting in poor prognoses that include intellectual disability, persisting seizures, and psychiatric conditions. For patients with treatment resistance to other modalities for LGS, a further option is surgical intervention. Evaluation for surgery should involve interictal electroencephalogram (EEG), magnetic resonance imaging (MRI) analysis, and age-appropriate neuropsychological/developmental assessment. Resective surgery, where seizure foci are removed, successfully controls seizures in many cases, particularly where lesionectomy or lobar resections are appropriate. Recent studies of resective surgery on individuals with LGS show promising results, with a high percentage of patients having improved seizure control. Corpus callosotomy is a palliative surgical approach that aims at controlling potentially injurious seizures, for example, atonic or drop seizures, by preventing the bilateral spread of epileptic activity. Once associated with a high risk for morbidity and mortality, microsurgical techniques and surgery limited to the anterior region of the callosum have greatly diminished complications of corpus callosotomy surgery. Vagus nerve stimulation, another palliative procedure, offers rates of seizure improvement similar to those of corpus callosotomy, with the exception of atonic seizure for which corpus callosotomy may lead to a greater reduction. Recent advances in surgical techniques offer encouraging options for treatment of LGS.


The early induction of suppressor of cytokine signaling 1 and the downregulation of toll-like receptors 7 and 9 induce tolerance in costimulated macrophages.
Toll-like receptors (TLR) 7 and 9 transduce a cellular signal through the MyD88-dependent pathway and induce the production of inflammatory mediators against microbial nucleotide components. The repeated stimulation of TLR4 leads to endotoxin tolerance, but the molecular mechanisms of tolerance induced through the costimulation of individual TLR has not yet been established, although endosomal TLRs share signaling pathways with TLR4. In the present study, mouse macrophages were simultaneously stimulated with the TLR7 agonist, gardiquimod (GDQ), and the TLR9 agonist, CpG ODN 1826, to examine the mechanism and effector functions of macrophage tolerance. Compared with individual stimulation, the costimulation of both TLRs reduced the secretion of TNF-α and IL-6 through the delayed activation of the NF-κB pathway; notably, IL-10 remained unchanged in costimulated macrophages. This tolerance reflected the early induction of suppressor of cytokine signaling-1 (SOCS-1), according to the detection of elevated TNF-α secretion and restored NF-κB signaling in response to the siRNA-mediated abrogation of SOCS-1 signaling. In addition, the restimulation of each TLRs using the same ligand significantly reduced the expression of both TLRs in endosomes. These findings revealed that the costimulation of TLR7 and TLR9 induced macrophage tolerance via SOCS-1, and the restimulation of each receptor or both TLR7 and TLR9 downregulated TLR expression through a negative feedback mechanisms that protects the host from excessive inflammatory responses. Moreover, the insufficient and impaired immune response in chronic viral infection might also reflect the repeated and simultaneous stimulation of those endosomal TLRs.


Medullary carcinoma of the thyroid gland with sustentacular cell-like cells in a patient with multiple endocrine neoplasia, type IIA. Report of a case with ultrastructural and immunohistochemical studies.
We report a case of a medullary carcinoma of the left lobe of the thyroid gland that occurred in a 57-year-old woman. The patient had undergone surgery for treatment of a bilateral-functioning pheochromocytoma when she was 39 years old. A medullary carcinoma of the thyroid gland and/or a pheochromocytoma had also been diagnosed in other family members. The tumor was composed of cells arranged in nests and large sheets separated by fibrous stroma that contained amyloid deposits. Elongated cells with thin, branched cytoplasmic projections that were strongly reminiscent of sustentacular cells usually found in paragangliomas were seen among the neoplastic cells. Immunohistochemical study showed a diffuse positive reaction for calcitonin and low-weight keratins (CAM 5.2) in neoplastic cells, whereas the sustentacular cell-like cells were positive for S100 protein. The reaction for thyroglobulin was negative. Electron microscopy disclosed large numbers of typical neurosecretory granules in the cytoplasm of tumor cells. The sustentacular cell-like cells showed elongated cytoplasmic processes and lacked neurosecretory granules. We concluded that the finding of sustentacular cell-like cells in a medullary carcinoma of the thyroid gland made its differential diagnosis from paraganglioma more problematic.


[The heat shock response and HSP70 gene expression in male germ cells].
Apoptosis of spermatogenic cells is an essential process that allows to maintain correct proportion between somatic and germ cells. In addition, apoptosis induced by cellular stress is an important checkpoint mechanism that eliminates damaged male germ cells. The response to cellular stress (e.g. hyperthermia) in somatic cells includes activation of the heat shock transcription factor 1 (HSF1) leading to induction and accumulation of the heat shock proteins (HSPs), mainly HSP70i, which allows cell survival. In major contrast, in meiotic and post-meiotic germ cells Hsp70i genes are not induced in elevated temperature. Instead, activation of HSF1 leads to caspase-3-dependent apoptosis and spermatogenic cells are actively eliminated. Although HSP70i proteins are repressed in spermatocytes and spermatids, another HSP70 proteins are specifically expressed in those cells, which are necessary for spermatogenesis. However, Hsp70.2/Hst70 gene, the major testis-specific Hsp70 expressed mostly in spermatocytes, is down-regulated by HSF1 and spermatogenic cells undergoing stress-induced apoptosis lack HSP70.2/HST70 protein.


2-18F-fluoro-2-deoxyglucose positron emission tomography in delirium.
Delirium is a common, serious, yet poorly understood syndrome. Growing evidence suggests cerebral metabolism is fundamentally disturbed; however, it has not been investigated using 2-18F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) in delirium. This prospective study thus explored FDG PET patterns of cerebral glucose metabolism in older inpatients with delirium. A particular emphasis was on the posterior cingulate cortex (PCC), a key region for attention, which is a central feature of delirium. Delirium scans were compared with post-delirium scans using visual analysis and semi-quantitative analysis with NeuroQ; 13 participants (8 female, median 84 y) were scanned during delirium, and 6 scanned again after resolution. On visual analysis, cortical hypometabolism was evident in all participants during delirium (13/13), and improved with delirium resolution (6/6). Using NeuroQ, glucose metabolism was higher post-delirium in the whole brain and bilateral PCC compared to during delirium ( p < 0.05). Greater metabolism in both PCCs correlated with better performance on a neuropsychological test of attention, the WAIS-IV Digit Span Test forwards, and with shorter delirium duration. This research found widespread, reversible cortical hypometabolism during delirium and PCC hypometabolism was associated with inattention during delirium.


Structural reassignment of a marine metabolite from a binaphthalenetetrol to a tetrabrominated diphenyl ether.
The structure of a reported natural product isolate has been revised from (S)-2,2'-dimethoxy-[1,1'-binaphthalene]-5,5',6,6'-tetraol to a known tetrabrominated diphenyl ether. After total synthesis of the reported binaphthalenetetrol was accomplished via a key reduction of a binaphtho-ortho-quinone, comparison of the physical properties and NMR spectroscopic data of the synthetic material indicated that the structure of the natural product isolate was incorrect. Evaluation of the authentic natural product suggested the structure is a tetrabrominated diphenyl ether, likely 3,5-dibromo-2-(3,5-dibromo-2-methoxyphenoxy)phenol.


The role of the People's Health Movement in putting the social determinants of health on the global agenda.
The People's Health Movement (PHM) is a global network of people oriented health professionals and activists, academcis and researchers, campaigners and people organizations that have actively promoted the re-endorsement of the 'Health for All' principles of the Alma Ata Declaration and the importance of social determinants of health and health care. The paper outlines a series of ongoing advocacy initiatives through a PHM - WHO advocacy circle that has consistently since 2001 nudged WHO to reaffirm the Alma Ata principles and focus on the social determinants of health. This has led to an evolving dialogue with PHM and the setting up of the WHO commission on social determinants of health, in which the PHM, is actively engaged.


Transfection of the Helicobacter pylori CagA gene alters MUC5AC expression in human gastric cancer cells.
Helicobacter pylori, the primary causative agent of stomach cancer, is known to affect gastric mucin expression. However, the underlying molecular mechanisms mediating this H. pylori-dependent effect remain unknown. In the present study, the effect of exogenous expression of the H. pylori virulence factor, CagA, on mucin 5AC oligomeric muscus/gel-forming (MUC5AC) expression was investigated using an in vitro model of the gastric mucosa. AGS cells were either untreated or transfected by a vector control (pCDNA3.1) or heterologous DNA, which induced CagA overexpression (pCDNA3.1-CagA). The expression and functionality of MUC5AC was analyzed using the reverse transcription-quantitative polymerase chain reaction and immunofluorescence assays. The expression of H. pylori-CagA in AGS cells was able to significantly upregulate MUC5AC expression compared to the vector control. In addition, immunofluorescence assays were able to validate increased MUC5AC expression following exogenous expression of H. pylori-CagA. The results of the present study revealed that the H. pylori-derived virulence factor CagA was able to increase the expression of MUC5AC. As this mucin constitutes an important ecological niche for H. pylori, this response may be involved in H. pylori colonization of the stomach.


Upper Airway Stimulation in Female Patients: Safety and Efficacy of a Novel Lateral Approach.
To describe a novel lateral approach for hypoglossal nerve stimulator (HNS) implantation in women and provide evidence for its safety and efficacy. Retrospective case series. Single academic medical center. We identified patients implanted with HNS by a single surgeon from January 2017 to December 2021. Patient characteristics, postoperative complications, surgical duration, response to therapy, and need for revision surgery were recorded. One hundred four patients were included, including 93 males and 11 females. The lateral approach for HNS implantation involves placing the chest incision for the implantable pulse generator and respiratory sensor lead vertically in the anterior axillary line instead of horizontally in the infraclavicular area. No changes are made to the stimulator lead placement. All female patients were implanted using a lateral approach and all male patients were implanted via the standard anterior approach. Half of the patients were implanted via a 2-incision technique. The median surgical time duration was equivalent in male and female patients (119 [interquartile range (IQR): 105-138] vs 126 [IQR: 115-141], respectively). Revision was required in 2 (18%) females versus 6 (6%) males (p = .17). There were equivalent rates of therapy response as well as postoperative complications. A more cosmetic lateral approach is feasible for HNS in female patients and has a similar rate of adverse events and therapy responsiveness. Additional considerations in female patients include the ability to tolerate mammography as well as HNS implantation in the setting of existing breast implants.


A novel strategy affords high-yield coupling of antibody to extremities of liposomal surface-grafted PEG chains.
Several methodologies for the preparation of polyethylene glycol-grafted immunoliposomes have been developed by attaching antibodies to the terminus of the polymer. Unilamellar liposomes were prepared containing a combination of a functionalized polyethylene glycol(3400) and an inert polyethylene glycol(2000) phosphatidylethanolamine derivate up to 5 mol%. The greater length of the functionalized polyethylene glycol derivate did not alter the liposomal sterical stability or the remote loading of doxorubicin. Anti-CD34 immunoliposomes were prepared by the reaction of maleimide-derivatized My10 antibody with generated thiol groups at the periphery of the liposomes and efficiencies of nearly 100% were obtained. The greater accessibility of the reactive group makes this strategy more efficient than others described. The immunoliposomes prepared bound specifically to CD34+ cells.


Comparative study of flavor in cholesterol-removed Gouda cheese and Gouda cheese during ripening.
This study was performed to compare the flavor compounds of cholesterol-removed Gouda cheese (CRGC) and those of Gouda cheese (control) during ripening. The CRGC was made using milk treated with cross-linked β-cyclodextrin (β-CD). The solid-phase microextraction (SPME) method was used to extract flavor compounds from Gouda cheese. In both CRGC and control cheese, 31 flavor compounds were identified, including 6 free fatty acids, 5 esters, 5 ketones, 1 aldehyde, 3 lactones, 5 alcohols, and 6 miscellaneous compounds. Free fatty acids were the most abundant flavor compounds quantified in CRGC and control cheese. In the early stage of ripening, concentrations of flavor compounds in CRGC and control cheese were 16.42 and 10.38 mg/kg, respectively. At 6 mo, they increased to 40.90 and 67.89 mg/kg, respectively. A group of esters was the second abundant flavor compound in CRGC and control cheese. At the initial stage of ripening, total concentrations of esters were 12.94 (CRGC) and 10.95 mg/kg (control) and they increased to 22.73 (CRGC) and 27.68 mg/kg (control). Total concentrations of ketones were 1.96 (CRGC) and 6.49 mg/kg (control) at the initial stage of ripening. After 6 mo of ripening, total concentrations reached 11.32 (CRGC) and 52.43 mg/kg (control). In the case of the lactones, at the early stage of ripening, total concentrations of CRGC and control cheese were 0.63 and 0.84mg/kg, respectively, and then increased to 1.73 (CRGC) and 3.25mg/kg (control) at the end of ripening. Based on the results of this study, the flavor compounds of CRGC and control showed slightly different profiles during ripening.


Quantification of Seasonal Variation in Daily Physical Activity in Individuals with Heart Failure and Implantable Cardioverter Defibrillator/Cardiac Resynchronisation Therapy Devices.
Understanding seasonal variation of daily physical activity (PA) in patients with heart failure (HF) has important implications for planning and interpretation of clinical trials, but the presence and magnitude of this seasonal variation in daily PA have yet to be established. The purpose of the present study was to determine the presence and magnitude of seasonal variation in daily PA in community-dwelling individuals with HF using several analytic approaches. Retrospective chart review of patients with HF and Medtronic implantable cardioverter defibrillator/cardiac resynchronisation therapy (ICD/CRT) devices. Data included in analyses (autocorrelation, analysis of covariance, one-way analysis of variance) were clinical characteristics, the patient activity measure of daily PA from the ICD/CRT devices, temperature and hours of daylight over the 1-year period of 1 November 2017-31 October 2018. One hundred and sixty-eight patients were included. Visual analysis and autocorrelation demonstrated seasonal variation in daily PA. Daily PA seasonal difference between winter and summer months was 0.4 hours per day/24 minutes per day/2.8 hours per week/14.9%. This seasonal effect on daily PA is significantly greater in those with ≤8 comorbid conditions and an overall activity level of >2.2 hours per day compared to those with multiple comorbidities and low overall activity (0.7 versus 0.1 hours per day, respectively). The present study affirms the seasonality of daily PA in a cohort of patients with HF and ICD/CRT devices and reveals a disproportionate seasonal effect on those with fewer comorbidities and higher overall activity levels. Seasonal variation should be accounted for when interpreting change in daily PA in clinical practice and when designing and interpreting results of clinical trials investigating interventions to improve daily PA.


Localization of Alkaline Phosphatase and Cathepsin D during Cell Restoration after Colchicine Treatment in Primary Cultures of Fetal Rat Hepatocytes.
Localization of alkaline phosphatase (ALP) and cathepsin D (CAPD) in primary cultures of fetal rat hepatocytes was examined using double immunofluorescent staining in order to investigate the relationship between lysosome movement and the fate of ALP during cell restoration after microtubule disruption by colchicine. At 3 hr and 24 hr after colchicine treatment, numerous coarse dots containing ALP were observed throughout the cytoplasm, and some of these showed colocalization with CAPD. At 48 hr and 72 hr after colchicine treatment, although most of the dots containing ALP in the cytoplasm disappeared, dots containing CAPD remained. The present results suggest that the denatured ALP proteins remaining in the cytoplasm of hepatocytes during cell restoration after colchicine treatment are digested by lysosomes.


An analysis of linkage disequilibrium in the interleukin-1 gene cluster, using a novel grouping method for multiallelic markers.
In population- and family-based association studies, it is useful to have some knowledge of the patterns of linkage disequilibrium that exist between markers in candidate regions. When such studies are carried out with multiallelic markers, it is often convenient to group the alleles into a biallelic system, for analysis. In this study, we specifically examined the interleukin-1 (IL-1) gene cluster on chromosome 2, a region containing candidates for many inflammatory and autoimmune disorders. Data were collected on eight markers, four of which were multiallelic. Using these data, we investigated the effect of three allele-grouping strategies, including a novel method, on the detection of linkage disequilibrium. The novel approach, termed the "delta method," measures the deviation from the expected haplotype frequencies under linkage equilibrium, for each allelic combination. This information is then used to group the alleles, in an attempt to avoid the grouping together of alleles at one locus that are in opposite disequilibrium with the same allele at the second locus. The estimate haplotype frequencies (EH) program was used to estimate haplotype frequencies and the disequilibrium measure. In our data it was found that the delta method compared well with the other two strategies. Using this method, we found that there was a reasonable correlation between disequilibrium and physical distance in the region (r=-.540, P=.001, one-tailed). We also identified a common, eight-locus haplotype of the IL-1 gene cluster.


The modulation of apolipoprotein E gene expression by 3,3'-5-triiodothyronine in HepG2 cells occurs at transcriptional and post-transcriptional levels.
The regulation of the synthesis and secretion of apolipoprotein E (apoE) is incompletely understood. This study examines the mechanisms responsible for regulating apoE gene expression in HepG2 cells by thyroid hormone (3,3'-5-triiodothyronine). The secretion rate of apoE was by thyroid hormone increased (1.5-1.8-fold) in pulse/chase experiments. Thyroid hormone doubled apoE mRNA concentration as determined by Northern-blot analysis. Inhibition of protein synthesis by cycloheximide increased the thyroid-hormone-induced stimulation of apoE mRNA. This suggests that the synthesis of new protein is not required for thyroid hormone to stimulate apoE mRNA. Actinomycin D was used to inhibit new transcription; there was a more rapid degradation of mature apoE mRNA in thyroid hormone-treated HepG2 cells than in control cells, suggesting that thyroid hormone acts post-transcriptionally to regulate apoE gene expression. Cycloheximide blocked the action of thyroid hormone, suggesting that thyroid hormone regulates the turnover of apoE mRNA via the synthesis of de novo protein. Nuclear run-on transcription assays demonstrated that thyroid hormone stimulated apoE gene transcription threefold in 24 h. These findings indicate that the expression of the apoE gene is controlled at both transcriptional and post-transcriptional loci by the thyroid hormone.


[Scanning electron microscopy of injection replicas of the cardiac microvessels].
The paper concerns three-dimensional study of the organization of the subepicardial network of the blood and lymphatic microvessels of the heart with the aid of scanning electron microscopy of the injected replicas. It is established that the arterioles have regular orientation of the imprints of the nucleus-containing zone of endotheliocytes. The capillaries belonging to the subepicardial network form a thick mesh and are strictly oriented along the muscular bundles. There is no characteristic relief on the surface of the capillaries. The study of the relief of the post-capillary venules made it possible to record different orientation of the imprints of the nuclei-containing zones of endotheliocytes on their surface. The study of structure of "leaks" formed as a result of leaking of resin from the venular segments of the bed enabled one to elicit their passage into the lymphatic capillaries. The latter are represented by flattened tubes, placed over the blood vessels.


Is your ethics committee efficient? Using "IRB Metrics" as a self-assessment tool for continuous improvement at the Faculty of Tropical Medicine, Mahidol University, Thailand.
Tensions between researchers and ethics committees have been reported in several institutions. Some reports suggest researchers lack confidence in the quality of institutional review board (IRB) reviews, and that emphasis on strict procedural compliance and ethical issues raised by the IRB might unintentionally lead to delays in correspondence between researchers and ethics committees, and/or even encourage prevarication/equivocation, if researchers perceive committee concerns and criticisms unjust. This study systematically analyzed the efficiency of different IRB functions, and the relationship between efficiency and perceived quality of the decision-making process. The major purposes of this study were thus (1) to use the IRB Metrics developed by the Faculty of Tropical Medicine, Mahidol University, Thailand (FTM-EC) to assess the operational efficiency and perceived effectiveness of its ethics committees, and (2) to determine ethical issues that may cause the duration of approval process to be above the target limit of 60 days. Based on a literature review of definitions and methods used and proposed for use, in assessing aspects of IRB quality, an "IRB Metrics" was developed to assess IRB processes using a structure-process-outcome measurement model. To observe trends in the indicators evaluated, data related to all protocols submitted to the two panels of the FTM-EC (clinical and non-clinical), between January 2010-September 2013, were extracted and analyzed. Quantitative information based on IRB Metrics structure-process-outcome illuminates different areas for internal-process improvement. Ethical issues raised with researchers by the IRB, which were associated with the duration of the approval process in protocol review, could be considered root causes of tensions between the parties. The assessment of IRB structure-process-outcome thus provides a valuable opportunity to strengthen relationships and reduce conflicts between IRBs and researchers, with positive outcomes for all parties involved in the conduct of human-subject research.


Identification of 58 Mutations (26 Novel) in 94 of 109 Symptomatic Spanish Probands with Protein C Deficiency.
Presently, no data on the molecular basis of hereditary protein C (PC) deficiency in Spain is available. We analyzed the PC gene (PROC) in 109 patients with symptomatic PC deficiency and in 342 relatives by sequencing the 9 PROC exons and their flanking intron regions. In 93 probands, we found 58 different mutations (26 novel). Thirty-seven consisted of a nucleotide change, mainly missense mutations, 1 was a 6-nucleotide insertion causing the duplication of 2 amino acids, and 4 were deletions of 1, 3, 4, and 16 nucleotides. Nine mutations caused type II deficiencies, with the presence of normal antigen levels but reduced anticoagulant activity. Using a PC level of 70% as lowest normal limit, we found no mutations in 16 probands and 25 relatives with PC levels ≤ 70%. On the contrary, 4 probands and 12 relatives with PC levels > 70% carried the mutation identified in the proband. The spectrum of recurrent mutations in Spain is different from that found in the Netherlands, where the most frequent mutations were p.Gln174* and p.Arg272Cys, and is more similar to that found in France, where the most frequent were p.Arg220Gln and p.Pro210Leu. In our study, p.Val339Met (9 families), p.Tyr166Cys (7), p.Arg220Gln (6), and p.Glu58Lys (5) were the most prevalent. This study confirms the considerable heterogeneity of the genetic abnormality in PC deficiencies, and allowed genetic counseling to those individuals whose PC levels were close to the lower limit of the normal reference range.


Clinical experience with an oral anticoagulant in children.
Nineteen cardiac patients were given warfarin sodium to prevent thrombosis and embolism. Empirical dosage resulted in long hospital stays to obtain a stable therapeutic prothrombin time. Using a dosage of 0 therefore 5-0 therefore 7 mg/kg, therapeutic levels were achieved in a much shorter time. When prothrombin time was excessive, it was successfully reduced with vitamin K or plasma. A haematoma in one case and haematuria in another were easily controlled. Warfarin sodium appears to be appropriate and effective for children requiring anticoagulants within the above dosage limits and with meticulous follow-up.


Effectiveness of immunomodulating treatment (thymostimulin) in chronic obstructive pulmonary disease.
We conducted a prospective randomized study to assess the effect of thymostimulin in patients with long-standing chronic obstructive pulmonary disease (COPD) during a 1-year follow-up. A total of 38 patients in the intervention group and 40 in the control group received standard treatment for COPD. Patients in the intervention group were also given thymostimulin intramuscularly (1 mg/kg day for the 1st week followed by once a week for 6 months). At the end of the study period, patients treated with thymostimulin showed a statistically significant lower number of exacerbations and hospital admissions as compared with controls. However, there were no changes in the number of patients with severe or moderate impairment of respiratory function throughout the study period. No significant differences were found by Multitest or in serum concentrations of immunoglobulins and T-cell subsets before and after thymostimulin treatment. We conclude that treatment with thymostimulin is effective in the prevention of COPD exacerbations acting on the cellular immune response involved in bronchopulmonary defense.


Experiences of cognitive stimulation therapy (CST) in Brazil: a qualitative study of people with dementia and their caregivers.
There is a lack of investment in psychosocial treatments for people with dementia in Brazil. Cognitive Stimulation Therapy (CST) is a group-based intervention that has shown to have benefits on activities of daily living and mood for people with dementia in Brazil. This study aims to explore the experiences and perceived changes following CST groups. Individual interviews were conducted with the participants of the group (n = 12) and their caregivers (n = 11). Framework analysis was used to inspect the data. Two main themes have emerged: 'Personal benefits of being part of the group', containing two subthemes: 'Benefits for caregivers' and 'Benefits for person with dementia' and 'Day-to-day changes', containing seven subthemes; 'Memory', Sociability', 'Language', 'Mood', 'Orientation', 'Everyday activities' and 'Behavioural and psychological symptoms'. Results suggest that CST groups led to perceived personal benefits for the people with dementia and caregivers and that there are perceived changes for the participants of the groups.


NLRP3 Deficiency Attenuates Renal Fibrosis and Ameliorates Mitochondrial Dysfunction in a Mouse Unilateral Ureteral Obstruction Model of Chronic Kidney Disease.
Background and Aims. The nucleotide-binding domain and leucine-rich repeat containing PYD-3 (NLRP3) inflammasome has been implicated in the pathogenesis of chronic kidney disease (CKD); however, its exact role in glomerular injury and tubulointerstitial fibrosis is still undefined. The present study was performed to identify the function of NLRP3 in modulating renal injury and fibrosis and the potential involvement of mitochondrial dysfunction in the murine unilateral ureteral obstruction (UUO) model of CKD. Methods. Employing wild-type (WT) and NLRP3-/- mice with or without UUO, we evaluated renal structure, tissue injury, and mitochondrial ultrastructure, as well as expression of some vital molecules involved in the progression of fibrosis, apoptosis, inflammation, and mitochondrial dysfunction. Results. The severe glomerular injury and tubulointerstitial fibrosis induced in WT mice by UUO was markedly attenuated in NLRP3-/- mice as evidenced by blockade of extracellular matrix deposition, decreased cell apoptosis, and phenotypic alterations. Moreover, NLRP3 deletion reversed UUO-induced impairment of mitochondrial morphology and function. Conclusions. NLRP3 deletion ameliorates mitochondrial dysfunction and alleviates renal fibrosis in a murine UUO model of CKD.


Comparison of two suspension arrays for simultaneous detection of five biothreat bacterial in powder samples.
We have developed novel Bio-Plex assays for simultaneous detection of Bacillus anthracis, Yersinia pestis, Brucella spp., Francisella tularensis, and Burkholderia pseudomallei. Universal primers were used to amplify highly conserved region located within the 16S rRNA amplicon, followed by hybridized to pathogen-specific probes for identification of these five organisms. The other assay is based on multiplex PCR to simultaneously amplify five species-specific pathogen identification-targeted regions unique to individual pathogen. Both of the two arrays are validated to be flexible and sensitive for simultaneous detection of bioterrorism bacteria. However, universal primer PCR-based array could not identify Bacillus anthracis, Yersinia pestis, and Brucella spp. at the species level because of the high conservation of 16S rDNA of the same genus. The two suspension arrays can be utilized to detect Bacillus anthracis sterne spore and Yersinia pestis EV76 from mimic "write powder" samples, they also proved that the suspension array system will be valuable tools for diagnosis of bacterial biothreat agents in environmental samples.


Quantum state tomography of dissociating molecules.
Using tomographic reconstruction we determine the complete internuclear quantum state, represented by the Wigner function, of a dissociating I2 molecule based on femtosecond time resolved position and momentum distributions of the atomic fragments. The experimental data are recorded by timed ionization of the photofragments with an intense 20 fs laser pulse. Our reconstruction method, which relies on Jaynes's maximum entropy principle, will also be applicable to time resolved position or momentum data obtained with other experimental techniques.


Rimantadine effects on the elasticity of bilayer lipid membranes and on ion transport through gramicidin D channels.
The effect of the antiviral preparation rimantadine on lipid bilayer membranes (BLM) was studied by measuring the modulus of elasticity in the direction normal to the surface (E perpendicular) and by estimating the conductance lambda, the lifetime tau of single gramicidin D channels (GRD), and the coefficient of nonlinearity beta of current voltage characteristics (IVC) of GRD-modified BLM. Rimantadine induced a nonmonotonic change in E perpendicular of BLM prepared from a mixture of egg lecithin with cholesterol: at relatively low rimantadine concentrations (0-40 micrograms/ml) E perpendicular first increased, reached a maximum and started to decrease. The effectivity of rimantadine was dependent on the cholesterol concentration in the BLM. Changes in E perpendicular suggest an increased ordering of the lipid bilayer at low rimantadine concentrations and formation of clusters of the preparation at concentrations exceeding those necessary to obtain maximal values of E perpendicular for the given BLM lipid composition. Rimantadine concentrations lifetime by approximately 20 percent, affected the degree of IVC nonlinearity and superlinearity of GRD-modified membranes, which suggests some effect on the height of the barrier at the ionic channel mouth and in its centre.


A quantitative and visual examination of sealed restorative specimens following exposure to artificial aging.
Low-viscosity polymer resins, or surface sealants (SSs), have been utilized as a means of finalizing the polishing step following the placement of composite resin restorations. The aim of this study was to measure the surface roughness (Ra) of composite resins treated with different SSs before and after exposure to an accelerated artificial aging protocol. The study included 5 experimental groups of composite resin discs (TPH Spectra ST) treated with different SSs (PermaSeal, Embrace WetBond Seal-n-Shine, OptiGuard, BisCover LV, and DuraFinish) and a control group consisting of untreated discs (n = 6 per group). The discs were prepared by inserting composite resin in 10 × 1-mm rings, covering the ring and material with a transparent strip, compressing the assembly between glass slides, and polymerizing through the slides on each side for 40 seconds with an LED curing light. Each disc except for the control specimens received a coating of the selected SS followed by application of a transparent matrix strip and then light polymerization for 20 seconds using an LED light source. Surface roughness measurements were obtained with a digital contact profilometer at baseline (immediately after polymerization) and following exposure to a thermocycling regimen to simulate aging. The data were analyzed using 2-way analysis of variance and post hoc Student-Newman-Keuls test with significance set at P < 0.05. There were no statistically significant differences among the groups at baseline. There were no statistically significant differences between the baseline and post-thermocycling Ra measurements except among the DuraFinish specimens, which were significantly rougher than all other groups after accelerated artificial aging. The use of SSs for the initial insertion and possibly for the long-term maintenance of composite resins could be minimally beneficial for restoration maintenance if a transparent covering medium is utilized during polymerization. However, due to the effects caused by formation of an oxygen-inhibited layer of unpolymerized monomers if a covering medium is not used, the results suggest the benefits do not offset the costs considering both gloss and Ra surface-testing parameters.


Association between enteric protozoan parasites and gastrointestinal illness among HIV- and tuberculosis-infected individuals in the Chowke district, southern Mozambique.
Human immune deficiency virus (HIV) and tuberculosis (TB) infections remain major public health issues globally, particularly in sub-Saharan Africa. Impairment of both cell-mediated and humoral immunity by HIV and/or TB infections may limit the host's defences against other pathogens, including the diarrheagenic protozoan Cryptosporidium spp., Giardia intestinalis, and Entamoeba histolytica. During September-December 2015 a cross-sectional study was conducted to assess the prevalence and molecular diversity of these enteric parasites among HIV- and/or TB-infected patients at a medical reference centre in Chowke district, southern Mozambique. A total of 99 stool specimens were initially screened by direct microscopy and further confirmed and characterised by molecular methods. DNA sequence analyses of the genes encoding the small subunit ribosomal RNA and the 60-kDa glycoprotein were used for the typing and sub-typing of Cryptosporidium isolates, respectively. G. intestinalis-positive isolates by real-time PCR were subsequently typed at the glutamate dehydrogenase locus. Differential diagnosis of E. histolytica/dispar was achieved by real-time PCR. G. intestinalis (8.1%) was the enteric protozoan more frequently detected, followed by Cryptosporidium spp. (7.1%), and Entamoeba histolytica/dispar (6.1%). Two HIV-infected (but not TB-infected) patients harbour G. intestinalis and Cryptosporidium spp. co-infections. Two (29%) G. intestinalis isolates were successfully characterised, revealing the presence of known AII and novel BIV genotypes. Four (57%) Cryptosporidium isolates were unmistakeable assigned to C. hominis, identifying two (IbA10G2 and IdA22) sub-types. Cryptosporidium infections were not associated to diarrhoea in HIV-positive patients, probably because improved immune function in the affected individuals due to antiretroviral therapy. G. intestinalis was considered a non-opportunistic pathogen, whereas the presence of E. histolytica could not be confirmed by molecular methods. Based on their common presence in the studied clinical population, we recommend the effective diagnosis and treatment of these enteropathogens for improving the management of HIV and TB patients.


A microbiological study of polyarthritis in slaughter pigs.
Arthritic joints obtained from 50 freshly slaughtered pig carcasses condemned for polyarthritis were studied microbiologically. A routine technique was developed for aseptically opening joints to obtain material for microbiological examination. A standard series of culture media for the primary isolation of arthritogenic agents were used in the examination of each affected joint. The microbiological study cultured for isolation of the following microorganisms: Erysipelothrix rhusiopathiae, Corynebacterium pyogenes, Staphylococcus aureus, Escherichia coli, Streptococcus spp., Haemophilus spp., Mycoplasma spp., Salmonella spp., Chlamydia, and viruses.E. rhusiopathiae was found to be responsible for 48% of the cases of arthritis and Streptococcus spp., C. pyogenes and S. aureus for 20%, 4%, and 2% respectively; no microorganisms were cultured from 26% of the arthritic joints.


Postpartum perforation of the colon due to endometriosis.
A case is reported of a ruptured endometriotic lesion following childbirth. Immediately after her second delivery, the 34-year-old parturient developed acute abdominal pain. At operation a ruptured left-sided ovarian abscess with a fistula to the colon was found. Endometriosis was present in the ovarian wall and the adjacent colon. Endometriosis as a cause of acute abdominal pain during pregnancy should be kept in mind.


Benign prostatic hyperplasia (BPH) requiring transurethral resection in freshly transplanted renal allograft recipients.
With recent progress in surgery and immunosuppression, more and more older men receive a kidney transplant. Thus, it is likely that the incidence of BPH in male transplant recipients is growing in parallel with age. Nonetheless, no data exist about diagnostic parameters for BPH in freshly transplanted male kidney allograft recipients. We evaluated whether established diagnostic and therapeutic criteria for BPH are valid for the evaluation of renal transplant recipients. BPH was diagnosed in 8 of 11 recipients older than 55 years. In all freshly transplanted renal allograft recipients, lower urinary tract symptoms (LUTS) were detected using an international prostate symptoms score (IPSS). This score was 9.6 +/- 7.1 in patients without BPH, and significantly higher with 21.1 +/- 4.3 in patients with BPH. In receiver-operating characteristics (ROC) curve analysis a cut-off of 15.5 was calculated to distinguish best between BPH and non-BPH giving an accuracy of 90.2%. Acute urinary retention (AUR) was the predominant sign, which occurred in all BPH patients but only in 6.9% in non-BPH patients. Bladder outlet obstruction (BOO) was also common with a reduced uroflow with 9.5 +/- 2.2 ml/sec in non-BPH and 3.0 +/- 1.8 ml/sec in BPH (8/11 BPH-patients developed AUR prior to measurement). By digital rectal examinations, benign prostate enlargement was estimated as minimal in 10 of 11 cases of BPH. In urethrocystoscopy kissing lobes were detected in all cases of BPH. Since medical treatment with alpha-receptor antagonists was not successful, a surgical procedure using a transurethral resection was performed without any complications in all cases. Symptoms did not recur after resection, and BOO improved with increased uroflow measurements with 12.3 +/- 4.8 ml/sec 8 days after resection. We conclude that LUTS and BOO are common in freshly transplanted renal allograft recipients. The sudden onset of outlet obstruction without the potentiality of adaptation of urinary bladder may effect lower urinary tract symptoms and bladder outlet obstruction. We conclude that an elevated IPSS over 15.5 in combination with AUR and typical urethrocystoscopy results are the best methods to diagnose BPH. Conversely, our results indicate that uroflowmetry and digital rectal examination are neither sensitive nor specific. In addition, once BPH has been diagnosed and treatment with receptor antagonists does not relieve urinary tract symptoms, surgical resection should be considered.


Transcatheter valve-in-valve aortic valve replacement with bioprosthetic valve Fracture/Stretching technique in a degenerated mitroflow valve.
We describe a successful bioprosthetic annular stretching in a patient with severe prosthetic aortic valve stenosis from a degenerated 19-mm Mitroflow valve (Sorin Group USA Inc, Arvada, CO, USA). This technique allowed for implantation of a 23-mm Evolut-R Pro valve (Medtronic, Minneapolis, MN, USA) with significant improvement in hemodynamics after prosthetic annular stretching. We have also summarized other case series and case reports which have previously described similar techniques. <Learning objective: Transcatheter valve-in-valve procedure may not be feasible in certain patients who have a relatively smaller size bioprosthetic valve. Cracking/stretching the annular ring of the smaller prosthetic valve to deploy a larger transcatheter valve is a potential option in these patients. Clinicians must be cognizant of the possible pitfalls, contraindications, and other technical aspects to choose the right patient for this procedure.>.


Increased HLA-DMB expression in the tumor epithelium is associated with increased CTL infiltration and improved prognosis in advanced-stage serous ovarian cancer.
To evaluate the possible mechanisms influencing the infiltration of CD8 T lymphocytes into the tumor epithelium of advanced-stage serous ovarian cancers. Immunohistochemical localization of CD8 T lymphocytes was done on a homogeneous population of 184 high-grade, advanced-stage serous ovarian cancer tissue specimens. Microarray analysis was done on microdissected tumor epithelium from 38 specimens to identify genes up-regulated or down-regulated in specimens with differing numbers of tumor-infiltrating CD8 T lymphocytes. Quantitative real-time PCR and immunohistochemistry were used to validate a candidate gene. Univariate and multivariate survival analyses were done combining CD8 T lymphocyte number and HLA-DMB expression with standard prognostic factors. Marked CD8 T lymphocyte infiltration of the tumor epithelium is associated with a 20-month improvement in median overall survival. Additionally, when combined with cytoreduction status and age, CD8 T lymphocyte status is an independent prognostic factor for survival. Microarray analysis showed HLA-DMB, a component of the MHC II antigen presentation machinery, to be differentially expressed in specimens with an abundance of tumor-infiltrating CD8 T lymphocytes. This relationship was validated at both mRNA and protein levels. As well, high HLA-DMB expression in the tumor epithelium was associated with a significant improvement in median overall survival in both univariate and multivariate analyses. Tumor cell expression of HLA-DMB is associated with increased numbers of tumor-infiltrating CD8 T lymphocytes and both are associated with improved survival in advanced-stage serous ovarian cancer.


Is the randomized controlled drug trial in Europe lagging behind the USA?
Performance of randomized controlled drug trials (drugRCTs) adds to the scientific output, scientific knowledge, scientific training and up-to-date status of healthcare and may drive economy. The purpose of this study was to benchmark Europe's position on drugRCTs relative to the rest of the world, and to identify factors that may drive this performance. The number of scientific publications on drugRCTs, indexed in PubMed and Thomson Scientific/Web of Science database over the period 1995-2004, was used as a proxy measure for the quantitative drugRCT output. The international citation impact of these publications was used as a proxy measure for the qualitative drugRCT output. Country's origin of 103 211 publications was determined. After adjustment for population size, the number of drugRCT publications from Europe, USA and Australia/Japan was 102, 124 and 44 publications per million inhabitants, respectively. The proportional increase in publication output from 1995 until 2004 was lower in Europe compared with the USA and Australia/Japan (29.1, 40.1 and 63.4%, respectively). The number of citations per publication was 4.9 in Europe, 7.0 in the USA and 3.4 in Australia/Japan. Within Europe, the UK, Germany and Italy produced most publications. Country-specific factors associated with publication output in Europe were the number of pharmaceutical companies with headquarters in a country (R(2) = 0.71, P < 0.001), national R&D expenditures by pharmaceutical companies (R(2) = 0.63, P < 0.001) and health-related R&D expenditures by national governments (R(2) = 0.22, P = 0.052). When adjusted for population size, quantitative and qualitative performance of drugRCTs in Europe lags behind the USA but is ahead of Australia/Japan. Several factors appear to explain the differences, among which are the number of headquarters of pharmaceutical companies in a country, the research expenditures by pharmaceutical companies, as well as health-related R&D expenditures of a country. To enhance and strengthen Europe's position, researchers may strengthen their collaborations with local pharmaceutical companies, and national governments could increase their budgets for medical research funding.


The sense of smell: genomics of vertebrate odorant receptors.
Olfactory receptor (OR) proteins interact with odorant molecules in the nose, initiating a neuronal response that triggers the perception of a smell. The OR family is one of the largest known mammalian gene families, with around 900 genes in human and 1500 in mouse. After discounting pseudogenes, the functional repertoire in mouse is more than three times larger than that of human. OR genes encode G-protein-coupled receptors containing seven transmembrane domains. ORs are arranged in clusters of up to 100 genes dispersed in 40-100 genomic locations. Each neuron in the olfactory epithelium expresses only one allele of one OR gene. The mechanism of gene choice is still unknown, but must involve locus, gene, and allele selection. The gene family has expanded mainly by tandem duplications, many of which have occurred since the divergence of the rodent and primate lineages. Interchromosomal segmental duplications including OR genes have also occurred, but more commonly in the human than the mouse family. As a result, many human OR genes have several possible mouse orthologs, and vice versa. Sequence and copy number polymorphisms in OR genes have been described, which may account for interindividual differences in odorant detection thresholds.


DNA analysis of histocompatibility antigens: fragments from the recently identified DR loci.
1. The DR locus of class II histocompatibility antigens (HLA-DR) is routinely typed by microlymphocytotoxicity tests. However, the preparation of good antisera is a complex process which relies heavily on a well-defined cell panel. 2. We have studied homozygous typing-cells representing the most common DR specificities in order to determine their typing pattern at the DNA level. 3. Restriction fragment length polymorphism obtained using six restriction enzymes permitted us to identify most of the DR specificities, including recently described splits of the DRw6. Specific fragments were tentatively allocated to the three DRw52 alleles. 4. The number of beta genes present on DRw52 and DRw53 antigen carrying cells is also discussed.


A Wii Bit of Fun: A Novel Platform to Deliver Effective Balance Training to Older Adults.
Falls and fall-related injuries are symptomatic of an aging population. This study aimed to design, develop, and deliver a novel method of balance training, using an interactive game-based system to promote engagement, with the inclusion of older adults at both high and low risk of experiencing a fall. Eighty-two older adults (65 years of age and older) were recruited from sheltered accommodation and local activity groups. Forty volunteers were randomly selected and received 5 weeks of balance game training (5 males, 35 females; mean, 77.18 ± 6.59 years), whereas the remaining control participants recorded levels of physical activity (20 males, 22 females; mean, 76.62 ± 7.28 years). The effect of balance game training was measured on levels of functional balance and balance confidence in individuals with and without quantifiable balance impairments. Balance game training had a significant effect on levels of functional balance and balance confidence (P < 0.05). This was further demonstrated in participants who were deemed at high risk of falls. The overall pattern of results suggests the training program is effective and suitable for individuals at all levels of ability and may therefore play a role in reducing the risk of falls. Commercial hardware can be modified to deliver engaging methods of effective balance assessment and training for the older population.


Isolation and characterization of a novel gossypol-degrading bacteria Bacillus subtilis strain Rumen Bacillus Subtilis.
The aim of the study was to isolate gossypol-degrading bacteria and to assess its potential for gossypol degradation. Rumen liquid was collected from fistulated cows grazing the experimental pasture. Approximately 1 mL of the rumen liquid was spread onto basal medium plates containing 2 g/L gossypol as the only source of carbon and was then cultured at 39°C to isolate gossypol-degrading bacteria. The isolated colonies were cultured for 6 h and then their size and shape observed by microscope and scanning electron microscope. The 16S rRNA gene of isolated colonies was sequenced and aligned using National Center for Biotechnology Information-Basic Local Alignment Search Tool. The various fermentation conditions, initial pH, incubation temperature, inoculum level and fermentationperiod were analyzed in cottonseed meal (CSM). The crude protein (CP), total gossypol (TG), and free gossypol (FG) were determined in CSM after fermentation with isolated strain at 39°C for 72 h. Screening results showed that a single bacterial isolate, named Rumen Bacillus Subtilis (RBS), could use gossypol as a carbon source. The bacterium was identified by 16S rDNA sequencing as being 98% homologous to the sequence of Bacillus subtilis strain GH38. The optimum fermentation conditions were found to be 72 h, 39°C, pH 6.5, moisture 50%, inoculum level 107 cell/g. In the optimum fermentation conditions, the FG and TG content in fermented CSM decreased 78.86% and 49% relative to the control. The content of CP and the essential amino acids of the fermented CSM increased respectively, compared with the control. The isolation of a gossypol-degrading bacterium from the cow rumen is of great importance for gossypol biodegradation and may be a valuable potential source for gossypol-degradation of CSM.


Universal exchange-driven phonon splitting in antiferromagnets.
We report a linear dependence of the phonon splitting Δω on the nondominant exchange coupling constant J(nd) in the antiferromagnetic transition-metal monoxides MnO, FeO, CoO, NiO, and in the frustrated antiferromagnetic oxide spinels CdCr(2)O(4), MgCr(2)O(4), and ZnCr(2)O(4). It directly confirms the theoretical prediction of an exchange-induced splitting of the zone-center optical phonon for the monoxides and explains the magnitude and the change of sign of the phonon splitting on changing the sign of the nondominant exchange also in the frustrated oxide spinels. The experimentally found linear relation [symbol:see text}Δω=βJ(nd)S(2) with slope β=3.7 describes the splitting for both systems and agrees with the observations in the antiferromagnets KCoF(3) and KNiF(3) with perovskite structure and negligible next-nearest neighbor coupling. The common behavior found for very different classes of cubic antiferromagnets suggests a universal dependence of the exchange-induced phonon splitting at the antiferromagnetic transition on the nondominant exchange coupling.


Chronic administration of myristic acid improves hyperglycaemia in the Nagoya-Shibata-Yasuda mouse model of congenital type 2 diabetes.
Previously, we demonstrated that myristic acid (14:0) increases levels of diacylglycerol kinase (DGK) δ, a key enzyme involved in type 2 diabetes exacerbation, and enhances glucose uptake in C2C12 myotube cells. Moreover, results from a population-based cohort study suggest that consumption of high-fat dairy products, which contain high amounts of myristic acid, is associated with a lower risk of developing type 2 diabetes. Taken together, we hypothesised that intake of myristic acid reduces type 2 diabetes risk in vivo. The aim of this study was to examine the glucose-lowering effect of myristic acid in Nagoya-Shibata-Yasuda (NSY) mice, a spontaneous model for studying obesity-related type 2 diabetes. Male NSY mice were orally administered vehicle (n = 9), 300 mg/kg of myristic acid (n = 14) or 300 mg/kg of palmitic acid (16:0) (n = 9) every other day from 4 weeks of age. Glucose and insulin tolerance tests were performed at weeks 18, 24 and 30, and weeks 20 and 26, respectively. DGKδ levels were measured in skeletal muscle from 32-36-week-old NSY mice via western blot. Chronic oral administration of myristic acid ameliorated glucose tolerance (24-28% decrease in blood glucose levels during glucose tolerance tests) and reduced insulin-responsive blood glucose levels (~20% decrease) in male NSY mice compared with vehicle and palmitic acid groups at 24-30 weeks of age (the age at which the severity of type 2 diabetes is exacerbated in NSY mice). Myristic acid also attenuated the increase in body weight seen in NSY mice. Furthermore, the fatty acid increased DGKδ levels (~1.6-fold) in skeletal muscle of NSY mice. These results suggest that the chronic oral administration of myristic acid improves hyperglycaemia by decreasing insulin-responsive glucose levels and reducing body weight, and that the fatty acid accounts for the diabetes protective properties of high-fat dairy products. Myristic acid is a potential candidate for the prevention and treatment of type 2 diabetes mellitus and its related diseases.


Wogonoside induces depalmitoylation and translocation of PLSCR1 and N-RAS in primary acute myeloid leukaemia cells.
Acute myeloid leukaemia (AML) comprises a range of disparate genetic subtypes, involving complex gene mutations and specific molecular alterations. Post-translational modifications of specific proteins influence their translocation, stability, aggregation and even leading disease progression. Therapies that target to post-translational modification of specific proteins in cancer cells represent a novel treatment strategy. Non-homogenous subcellular distribution of PLSCR1 is involved in the primary AML cell differentiation. However, the nuclear translocation mechanism of PLSCR1 remains poorly understood. Here, we leveraged the observation that nuclear translocation of PLSCR1 could be induced during wogonoside treatment in some primary AML cells, despite their genetic heterogeneity that contributed to the depalmitoylation of PLSCR1 via acyl protein thioesterase 1 (APT-1), an enzyme catalysing protein depalmitoylation. Besides, we found a similar phenomenon on another AML-related protein, N-RAS. Wogonoside inhibited the palmitoylation of small GTPase N-RAS and enhanced its trafficking into Golgi complex, leading to the inactivation of N-RAS/RAF1 pathway in some primary AML cells. Taken together, our findings provide new insight into the mechanism of wogonoside-induced nuclear translocation of PLSCR1 and illuminate the influence of N-RAS depalmitoylation on its Golgi trafficking and RAF1 signalling inactivation in AML.


Measurement of bound and pore water T1 relaxation times in cortical bone using three-dimensional ultrashort echo time cones sequences.
We present three-dimensional ultrashort echo time Cones (3D UTE Cones) techniques for quantification of total water T1 ( T1TW), bound water T1 ( T1BW), and pore water T1 ( T1PW) in vitro and in vivo using a 3 Tesla (T) scanner. T1TW, T1BW, and T1PW were measured with three-dimensional (3D) Cones and adiabatic inversion recovery Cone (IR-Cone) sequences. Two-dimensional (2D) nonselective ultrashort echo time (UTE) techniques, including saturation recovery, variable repetition times (TRs), and inversion recovery (IR) preparation approaches were compared with 3D-Cones techniques on bovine cortical bone samples (n = 8). The 3D Cones sequences were used to measure T1TW, T1BW, and T1PW in the tibial midshaft of healthy volunteers (n = 8). Comparable T1 images were achieved for cortical bone between 3D Cones and 2D UTE techniques as well as those published in the literature. The 3D Cones sequences showed a mean T1TW of 208 ± 22 ms, a mean T1PW of 545 ± 28 ms, and a mean T1BW of 131 ± 12 ms for bovine cortical bone; and a mean T1TW of 246 ± 32 ms, a mean T1PW of 524 ± 46 ms, and a mean T1BW of 134 ± 11 ms for the tibial midshaft of healthy volunteers. The 3D Cones sequences can be used for fast volumetric assessment of bound and pore water T1 images in vitro and in vivo. Magn Reson Med 77:2136-2145, 2017. © 2016 International Society for Magnetic Resonance in Medicine.


Alleviating heat stress effects in poultry: updates on methods and mechanisms of actions.
Heat stress is a threat that can lead to significant financial losses in the production of poultry in the world's tropical and arid regions. The degree of heat stress (mild, moderate, severe) experienced by poultry depends mainly on thermal radiation, humidity, the animal's thermoregulatory ability, metabolic rate, age, intensity, and duration of the heat stress. Contemporary commercial broiler chickens have a rapid metabolism, which makes them produce higher heat and be prone to heat stress. The negative effect of heat stress on poultry birds' physiology, health, production, welfare, and behaviors are reviewed in detail in this work. The appropriate mitigation strategies for heat stress in poultry are equally explored in this review. Interestingly, each of these strategies finds its applicability at different stages of a poultry's lifecycle. For instance, gene mapping prior to breeding and genetic selection during breeding are promising tools for developing heat-resistant breeds. Thermal conditioning during embryonic development or early life enhances the ability of birds to tolerate heat during their adult life. Nutritional management such as dietary manipulations, nighttime feeding, and wet feeding often, applied with timely and effective correction of environmental conditions have been proven to ameliorate the effect of heat stress in chicks and adult birds. As long as the climatic crises persist, heat stress may continue to require considerable attention; thus, it is imperative to explore the current happenings and pay attention to the future trajectory of heat stress effects on poultry production.


Lessons Learned for Pathogenesis, Immunology, and Disease of Erythrocytic Parasites: Plasmodium and Babesia.
Malaria caused by Plasmodium species and transmitted by Anopheles mosquitoes affects large human populations, while Ixodes ticks transmit Babesia species and cause babesiosis. Babesiosis in animals has been known as an economic drain, and human disease has also emerged as a serious healthcare problem in the last 20-30 years. There is limited literature available regarding pathogenesis, immunity, and disease caused by Babesia spp. with their genomes sequenced only in the last decade. Therefore, using previous studies on Plasmodium as the foundation, we have compared similarities and differences in the pathogenesis of Babesia and host immune responses. Sexual life cycles of these two hemoparasites in their respective vectors are quite similar. An adult Anopheles female can take blood meal several times in its life such that it can both acquire and transmit Plasmodia to hosts. Since each tick stage takes blood meal only once, transstadial horizontal transmission from larva to nymph or nymph to adult is essential for the release of Babesia into the host. The initiation of the asexual cycle of these parasites is different because Plasmodium sporozoites need to infect hepatocytes before egressed merozoites can infect erythrocytes, while Babesia sporozoites are known to enter the erythrocytic cycle directly. Plasmodium metabolism, as determined by its two- to threefold larger genome than different Babesia, is more complex. Plasmodium replication occurs in parasitophorous vacuole (PV) within the host cells, and a relatively large number of merozoites are released from each infected RBC after schizogony. The Babesia erythrocytic cycle lacks both PV and schizogony. Cytoadherence that allows the sequestration of Plasmodia, primarily P. falciparum in different organs facilitated by prominent adhesins, has not been documented for Babesia yet. Inflammatory immune responses contribute to the severity of malaria and babesiosis. Antibodies appear to play only a minor role in the resolution of these diseases; however, cellular and innate immunity are critical for the clearance of both pathogens. Inflammatory immune responses affect the severity of both diseases. Macrophages facilitate the resolution of both infections and also offer cross-protection against related protozoa. Although the immunosuppression of adaptive immune responses by these parasites does not seem to affect their own clearance, it significantly exacerbates diseases caused by coinfecting bacteria during coinfections.


Expanding the scope of cyclopropene reporters for the detection of metabolically engineered glycoproteins by Diels-Alder reactions.
Monitoring glycoconjugates has been tremendously facilitated by the development of metabolic oligosaccharide engineering. Recently, the inverse-electron-demand Diels-Alder reaction between methylcyclopropene tags and tetrazines has become a popular ligation reaction due to the small size and high reactivity of cyclopropene tags. Attaching the cyclopropene tag to mannosamine via a carbamate linkage has made the reaction even more efficient. Here, we expand the application of cyclopropene tags to N-acylgalactosamine and N-acylglucosamine derivatives enabling the visualization of mucin-type O-glycoproteins and O-GlcNAcylated proteins through Diels-Alder chemistry. Whereas the previously reported cyclopropene-labeled N-acylmannosamine derivative leads to significantly higher fluorescence staining of cell-surface glycoconjugates, the glucosamine derivative gave higher labeling efficiency with protein preparations containing also intracellular proteins.


Preventing occupational chemical eye injuries: important lessons from poison information centres.
Occupational exposure to hazardous substances is a major public health problem. In the workplace, eye exposures are common and can be a major cause of morbidity and disability. This commentary discusses the role of poison information centres in providing valuable information on the circumstances and causes of these incidents. As many eye exposures are easily preventable, there is a need to establish better safety practices in the workplace. Currently, both governments and labour organizations primarily employ injury statistics for the purpose of occupational health surveillance. Identifying risk factors associated with acute exposures in the workplace requires a comprehensive approach using a variety of information resources. Using information from poison information centres can provide invaluable insight into the specifics of the exposure, including the route(s) of exposure, the substances involved and the cause of the exposure. Exposure to hazardous substances can occur at various time points during work. A prospective study performed by the Dutch Poisons Information Centre showed that cleaning is a high-risk activity for occupational eye exposure. Patients were often exposed to chemical mixtures that frequently contained alkalis or acids. Symptoms following eye contact with chemicals can vary greatly depending on factors such as the type and concentration of the substance(s) involved, the duration of exposure and the time and duration of irrigation (first-aid measure). Eye contact will usually cause irritation, but in more severe cases, chemical burns will result. Recent studies demonstrate that occupational eye exposures often result in only relatively mild symptoms, such as pain, redness, lacrimation or temporary loss of vision. More severe symptoms, such as corneal abrasion, were reported rarely, which may be explained by prompt eye irrigation. To control risks to workers, a hierarchy of prevention and control measures has been established, which employers must take. If elimination or substitution of the dangerous substance is not possible, the exposure can be prevented or reduced by taking organizational (e.g., providing work instructions), technical (e.g., ventilation) and personal (e.g., wearing personal protective equipment) measures. The study performed by the Dutch Poisons Information Centre showed that organizational factors (such as lack of work instructions) and personal factors (such as time pressure and fatigue, and not (adequately) using personal protective equipment), were the main causes of occupational eye exposure. Poison information centres provide valuable information that can be used to develop prevention strategies to reduce the number of acute occupational exposures in the future. A multidisciplinary approach is essential to ensure that these preventive measures are actually applied in practice. Therefore, all organizations involved (including governments, labour organizations, medical professionals, occupational physicians, occupational hygienists, safety experts and poison information centres) must work closely together.


The evolution of an innovation: variations in medicaid managed care program extensiveness.
This article utilizes a theoretical framework of policy innovation, diffusion, and reinvention to investigate the evolving nature of Medicaid managed care programs over time. By estimating two separate models, one for primary care case management (PCCM) and a second for risk-based program enrollment, this study seeks to disentangle two different paths of learning (internal and external), investigate the potential effects of vertical diffusion of policy, and examine the impact of internal state characteristics on the extent of Medicaid managed care. With respect to diffusion and learning, the data reveal that earlier adopters implement more extensive programs. The data fail to reveal much internal learning, although there is evidence of some. External impacts are clear: managed care enrollments in neighboring states and changes in the federal waiver process affect states' decisions. Other policy choices are important: states with more generous Medicaid eligibility rules implement more extensive managed care programs. Complementing other studies of Medicaid, we find that politics and economics make a difference for the extent of managed care programs; unlike other Medicaid studies, we find no effect of race and ethnicity.


Interaction of protonated anticancer thiazines with water-insoluble phospholipids and antineoplastic agents.
A series of neuroleptic protonated phenothiazine derivatives (promethazine, promazine, triflupromazine, methotrimeprazine, propiomazine, trifluoperazine and fluphenazine), some with known anticancer properties, were complexed with water-insoluble antineoplastice agents such as 5-fluorouracil (5FU), methotrexate (MTX) and sulindac, as well as with components of biomembrane and synthetic phospholipids as possible models of cancer and microbial cells. In all cases water-soluble micellar inclusion adducts were formed exhibiting electron charge transfer complex behaviour, with the appearance of thazine free radicals. The thiazines sequestered the drugs and phospholipids in well-defined molar ratios (MR) parabolically-dependent on the dipole moments (mu) of the protonated phenothiazine derivatives. pH comparisons showed that the inclusion adducts followed a model in which the compounds were enveloped in the lipophilic interior of the thiazine aggregates, while the side-chains of the latter faced the aqueous environment. In the model experiment, interaction of the thiazines and the 5FU adducts with E. coli F' lac was additive to marginally synergistic, confirmed by the checkerboard technique. The parabolic dependence of the molar minimum inhibitory concentration of the thiazines and thiazine/5FU adducts on the thiazine dipole moments suggests that their primary loci of interaction are the cell wall or membrane phospholipid components. Thiazines, especially those with dipole moments centered on about 6 D, near which the lowest MR occurs, can act as effective carriers for insoluble or sparsely soluble drugs. Any new thiazine drug for use alone or as a carrier in anticancer therapy should be designed with this criterion in mind.


Case of B-cell lymphoma with rearrangement of the BCL1, BCL2, BCL6, and c-MYC genes.
We managed a peculiar case of lymphoma showing immunohistochemical overexpression of cyclin D1. At initial examination the patient had meningeal lymphomatosis and general lymphadenopathy. Histologic examination of biopsy specimens of inguinal lymph nodes showed tumor cells and vague nodular growth resembling lymphoblasts. The results of flow cytometric analysis were positive for CD10, CD20, CD103, and immunoglobulin G (IgG) and Ig kappa and were negative for CD5, CD23, and terminal deoxynucleotidyl transferase activity. Results of immunohistochemical analysis of paraffin-embedded specimens were positive for cyclin D1 and Bcl2 in the tumor cells. Sixty percent of tumor cells had positive results for MIB1/Ki67. Cytogenetic and molecular studies revealed tumor cells simultaneously had t(14;18)(q32;q21), t(11;22)(q13;q11), t(8;14)(q24;q32), and t(3;14)(q27;q32) with the rearrangement of BCL1, BCL2, BCL6, and c-MYC genes. Lymphadenopathy showed a quick and complete response to doxorubicin-containing systemic chemotherapy with rituximab, but the central nervous system disease progressed and killed the patient.


Implement of Biotic and Abiotic Stress for Enhancement and Production of Capsaicin in Suspension Cultures of <I>Capsicum annum</I> spp.
Pepper (Capsicum annuum L.) is one of the major vegetable and spice crops grown worldwide. This study highlighted the economic and importance process for in vitro capsaicin production from pepper plant. As well as to study the effect of MS medium supplemented with 2,4-D in combinations with 0.2 mg L-1 Kin. for callus and suspension production was implemented. As well as, the influence of A. niger as biotic and methyl jasmonate as abiotic elicitors on capsaicin accumulation was investigated. For this purpose, callus cultures were prepared from seeds of pepper and subcultured. After 28 days, calli formation (%), fresh weight (g/Jar) and dry weight (g/Jar) was calculated. Cell number and packed cell volume were calculated from their cell suspension. In the end, capsaicin was extracted and colorimetrically quantified. The highest percentage of calli formation was recorded with hypocotyl, leaf and root explants, respectively. The MS medium fortified with 3.0 mg L-1 2,4-D+0.2 mg L-1 Kin. In addition, the maximum P.C.V was recorded after 16 days of cultivation on the same medium. Furthermore, it was found that fortified MS medium with 1.5% of A. niger in combination with 100 μM of methyl jasmonate achieved of cell growth parameters and capsaicin accumulation in significant rate during 16 days of cultivation. Fortified of MS medium with 3.0 mg L-1 2,4-D+0.2 mg L-1 Kin. showed the optimized medium for both callus and suspension production. Moreover, augmentation of MS medium with 1.5% of A. niger in combination with 100 μM of methyl jasmonate enhanced of capsaicin accumulation in significant rate during 16 days of cultivation.


Computational Representations of Myocardial Infarct Scars and Implications for Arrhythmogenesis.
Image-based computational modeling is becoming an increasingly used clinical tool to provide insight into the mechanisms of reentrant arrhythmias. In the context of ischemic heart disease, faithful representation of the electrophysiological properties of the infarct region within models is essential, due to the scars known for arrhythmic properties. Here, we review the different computational representations of the infarcted region, summarizing the experimental measurements upon which they are based. We then focus on the two most common representations of the scar core (complete insulator or electrically passive tissue) and perform simulations of electrical propagation around idealized infarct geometries. Our simulations highlight significant differences in action potential duration and focal effective refractory period (ERP) around the scar, driven by differences in electrotonic loading, depending on the choice of scar representation. Finally, a novel mechanism for arrhythmia induction, following a focal ectopic beat, is demonstrated, which relies on localized gradients in ERP directly caused by the electrotonic sink effects of the neighboring passive scar.


[Acute respiratory distress syndrome complicating imported Plasmodium falciparum malaria].
A 25-year-old male, who had returned from the Republic of Mali in Africa, was admitted to our hospital because of a 3-day history of high fever, on the first of October 1996. He was diagnosed as Plasmodium falciparum malaria by peripheral blood smear. From the admission day he was treated with quinine HCL, 1,500 mg per day, and sulfamethoxazole 2,400 mg trimethoprim 480 mg per day, but on October 2nd blood examination showed 35% parasite density and he was given mefloquine. However he was complicated with DIC on October 3rd, ARDS on October 5th. By anti-coagulant therapy and methylprednisolone pulse therapy he became afebrile and respiratory function improved rapidly. ARDS should be emphasized as a severe complication of imported severe malaria.


miR-149-5p inhibits cell proliferation and invasion through targeting GIT1 in medullary thyroid carcinoma.
Previous studies indicate that miR-149 could both inhibit and promote the development of human cancer depending on the tumor type. GIT1 was found to play an important role in regulating cell migration. However, the specific function of miR-149-5p and GIT1 in the progression of medullary thyroid carcinoma (MTC) remains unknown. The purpose of this study was to confirm the function of miR-149-5p in MTC and explore its downstream regulation. Moreover, miR-149-5p level in MTC was detected via RT-quantitative PCR (RT-qPCR). GIT1 expression levels were assessed by RT-qPCR and western blot analysis. The cell proliferation and invasion were detected through MTT or Transwell assay respectively. In addition, miR-149-5p was identified to directly target GIT1 in MTC via dual luciferase assay. The results suggested that miR-149-5p level was obviously declined in MTC. Functionally, miR-149-5p overexpression inhibited proliferation and invasion. Moreover, miR-149-5p directly targeted GIT1 and was negatively associated with its expression in MTC. Conversely, GIT1 expression was obviously increased in MTC. GIT1 overexpression partially reversed the inhibitory action of miR-149-5p in MTC. miR-149-5p suppressed the proliferation and invasion of MTC cells through targeting GIT1, which would create new therapeutic avenues for MTC treatment.


Is the chimney graft technique a safe and feasible approach to treat urgent aneurysm and pseudoaneurysm of the abdominal aorta? An analysis of our experience and technical considerations.
The chimney graft (CG) technique, based on the deployment of a covered stent parallel to the aortic endograft, has been proposed to achieve a safe proximal fixation extending the sealing zone. We report our experience with the CG technique in an emergency setting. Between December 2010 and April 2012, 4 patients underwent the CG technique. The mean age was 79 (range 76-82 years) and 3 patients were men. The median aneurysm diameter was 64.7 mm (range 63-68 mm). Indications for CG were painful proximal para-anastomotic aneurysm in 2 cases and symptomatic juxtarenal aneurysm in the other 2. Target vessels were both the renal arteries. Technical success was achieved in 100% and no intraoperative complications occurred. No stent-related complications, or Type I endoleak, were detected. No death occurred during the postoperative course. Creatinine elevation was observed in 2 cases. At follow-up, no endoleaks or rupture occurred. One patient died of myocardial infarction 3 months after the procedure. The primary patency rate of covered stents was 100%. The CG technique seems to be safe and feasible with an excellent patency rate of covered stents and a low incidence of endoleaks. More evidence in the literature is needed to carry out a validation of this technique in an emergency.


Breed and sire effects on crossbred lamb production from Panama ewes and on spermatozoan midpiece length.
Three-hundred mature Panama-type range ewes were mated to Clun Forest, Dorset, Border Leicester, Polypay and Suffolk rams during the 1979 and 1980 breeding seasons. Sire breed and ram within breed effects on lamb growth, ewe reproduction, spermatozoan midpiece length (MPL) and midpiece length coefficient of variation (MPLCV) were examined. Associations among MPL and MPLCV and economically important traits also were assessed. Suffolk-sired lambs weighted .18, 2.0 and 1.5 kg more, at birth, weaning and post-weaning, respectively, than the average of all groups. Dorset-sired lambs had the lightest postweaning weight. Variation was greatest among Suffolk rams for average weaning and postweaning weights of their progeny. The Border Leicester breed had the least among ram variation for progeny weaning weight; while variation among Dorset rams was least for progeny postweaning weight. Fertility (ewes lambing/ewe exposed) and prolificacy (lambs born/ewe lambing) of the rams' mates were not influenced significantly by sire breed. Lamb mortality also was not influenced by breed of sire nor by rams within a breed. For variation in MPL, 26.4% was due to the breed effect (P less than or equal to .01) and 21.6% was attributable to ram variation within a breed (P less than or equal to .01). Clun Forest rams had the longest average MPL and greatest MPLCV, while Dorsets had the shortest MPL and smallest MPLCV. There were no important associations between either MPL or MPLCV and any of the economic traits.


Histologic differentiation of hepatocellular carcinoma from adenocarcinoma by a simple panel: evaluation of the pitfalls.
The histological differentiation of Hepatocellular carcinoma (HCC) from cholangiocarcinoma (CC) and metastatic adenocarcinoma (MA) of the liver is difficult in some cases and immunohistochemistry (IHC) is necessary for the diagnosis. HepPar-1 is a recently available antibody which seems to be very specific and sensitive for the diagnosis of HCC. MOC31 is an antibody directed against a cell surface glycoprotein and has been shown to be helpful in distinguishing between HCC and CC or MA as a negative marker in HCC. In this study we tried to apply these two markers for the diagnosis of HCC cases as a simple, useful and reliable panel. We selected 101 liver tumors which had proven diagnosis by several antibodies and cilinicopathologic correlation. The tumors with confirmed histologic diagnosis including 35 HCC, 58 MA, 7 CC and 1 combined HCC-CC.. HepPar-1 was positive in 30 of 35 cases of HCC; none of the other tumors were reactive for HepPar1 except for a case of metastatic gall bladder adenocarcinoma which showed areas of hepatoid differentiation in the H&E slides. MOC31 was positive in 5 of the HCC cases and stained 60 of 65 cases of MA. There were 4 cases of HCC with clear cell morphology, in most of which, IHC pattern was not diagnostic and further investigation was needed. As a conclusion the combination of positive Hepar1 and negative MOC31 is highly suggestive for HCC except for the clear cell variant. These two reliable markers are recommended for the initial step of differential diagnosis between HCC and MA and for the confirmation of the histologic diagnosis.


Cellular fibroma of the ovary containing Leydig cell hyperplasia: a case report.
Ovarian stromal tumors containing Leydig cell components are rare. Only a few cases of ovarian stromal Leydig cell tumors characterized by clusters of Leydig cells have been reported to date. Here, we present the first case report of a 65-year-old woman with a cellular fibroma of the ovary containing Leydig cell hyperplasia. Microscopic examination revealed the proliferation of spindle cells arranged in intersecting bundles with mild nuclear atypia and an average of 2-3 mitotic figures per ten high-power fields. Multifocal nests of polygonal cells with abundant eosinophilic cytoplasm and round nuclei were seen within the spindle cells. Final pathology of the tumor revealed a cellular fibroma including Leydig cell hyperplasia.


Transgenic Cross-Referencing of Inhibitory and Excitatory Interneuron Populations to Dissect Neuronal Heterogeneity in the Dorsal Horn.
The superficial dorsal horn (SDH, LI-II) of the spinal cord receives and processes multimodal sensory information from skin, muscle, joints, and viscera then relay it to the brain. Neurons within the SDH fall into two broad categories, projection neurons and interneurons. The later can be further subdivided into excitatory and inhibitory types. Traditionally, interneurons within the SDH have been divided into overlapping groups according to their neurochemical, morphological and electrophysiological properties. Recent clustering analyses, based on molecular transcript profiles of cells and nuclei, have predicted many more functional groups of interneurons than expected using traditional approaches. In this study, we used electrophysiological and morphological data obtained from genetically-identified excitatory (vGLUT2) and inhibitory (vGAT) interneurons in transgenic mice to cluster cells into groups sharing common characteristics and subsequently determined how many clusters can be assigned by combinations of these properties. Consistent with previous reports, we show differences exist between excitatory and inhibitory interneurons in terms of their excitability, nature of the ongoing excitatory drive, action potential (AP) properties, sub-threshold current kinetics, and morphology. The resulting clusters based on statistical and unbiased assortment of these data fell well short of the numbers of molecularly predicted clusters. There was no clear characteristic that in isolation defined a population, rather multiple variables were needed to predict cluster membership. Importantly though, our analysis highlighted the appropriateness of using transgenic lines as tools to functionally subdivide both excitatory and inhibitory interneuron populations.


In Vitro Susceptibility of Clinical Staphylococcus aureus Small-Colony Variants to β-Lactam and Non-β-Lactam Antibiotics.
The Staphylococcus aureus small-colony variant (SCV) phenotype has been associated with relapsing and antibiotic-refractory infections. However, little is known about the activities of antibiotics on clinical SCVs. Here, we demonstrated that SCVs without detectable auxotrophies were at least as susceptible to most β-lactam and non-β-lactam antibiotics in vitro as their corresponding clonally identical strains with a normal phenotype. After prolonged incubation, a regrowth phenomenon has been observed in gradient diffusion inhibition zones irrespective of the strains' phenotype.


Clinical management strategies and implications for parenteral nutrition drug shortages in adult patients.
Drug shortages affect every aspect of patient care, including and especially, nutrition therapy. The purpose of this review is to discuss current parenteral nutrition-related drug shortages, including causes and duration of the disruptions, and provide recommendations for managing specific nutritional shortages that minimize negative patient care outcomes. A general framework for the management of current and future shortages is presented.


Human Vault Nanoparticle Targeted Delivery of Antiretroviral Drugs to Inhibit Human Immunodeficiency Virus Type 1 Infection.
"Vaults" are ubiquitously expressed endogenous ribonucleoprotein nanoparticles with potential utility for targeted drug delivery. Here, we show that recombinant human vault nanoparticles are readily engulfed by certain key human peripheral blood mononuclear cells (PBMC), predominately dendritic cells, monocytes/macrophages, and activated T cells. As these cell types are the primary targets for human immunodeficiency virus type 1 (HIV-1) infection, we examined the utility of recombinant human vaults for targeted delivery of antiretroviral drugs. We chemically modified three different antiretroviral drugs, zidovudine, tenofovir, and elvitegravir, for direct conjugation to vaults. Tested in infection assays, drug-conjugated vaults inhibited HIV-1 infection of PBMC with equivalent activity to free drugs, indicating vault delivery and drug release in the cytoplasm of HIV-1-susceptible cells. The ability to deliver functional drugs via vault nanoparticle conjugates suggests their potential utility for targeted drug delivery against HIV-1.


High-Sensitivity Troponin I and Coronary Computed Tomography in Symptomatic Outpatients With Suspected CAD: Insights From the PROMISE Trial.
The goal of this study was to examine associations between concentrations of high-sensitivity troponin I (hsTnI) (measured by using a single-molecule counting method) and obstructive coronary artery disease (CAD) in 1,844 stable, symptomatic outpatients with suspected CAD randomized to undergo coronary computed tomography angiography (CTA) in the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial. Elevated concentrations of hsTnI are associated with CAD in patients with myocardial infarction. The meaning of hsTnI concentrations in stable symptomatic outpatients is not well understood. Clinical characteristics and CTA results (including coronary artery calcium [CAC] scores) were expressed across hsTnI quartiles. Determinants of hsTnI concentration were identified. Multivariable logistic regression identified independent predictors of obstructive CAD50 (≥50% stenosis in any vessel) and CAD70 (≥70% stenosis or ≥50% left main). The median hsTnI concentration was 1.5 ng/l; nearly all (98.5%) subjects had measurable hsTnI, and 6.1% had concentrations ≥99th percentile concentration for this assay (6 ng/l). Higher CAC scores, as well as more prevalent and diffuse CAD, was seen in upper hsTnI quartiles (all p < 0.001). Independent predictors of hsTnI concentrations included age, sex, and CAC score (all p < 0.05). After adjusting for demographic and clinical characteristics, log-transformed hsTnI concentrations were associated with obstructive CAD50 (odds ratio: 1.15 per interquartile range; p = 0.02) and CAD70 (odds ratio: 1.25 per interquartile range; p = 0.001). In stable symptomatic outpatients undergoing nonemergent coronary CTA for the diagnosis of suspected CAD, higher concentrations of hsTnI were associated with increasing presence and severity of coronary atherosclerosis. (Prospective Multicenter Imaging Study for Evaluation of Chest Pain [PROMISE]; NCT01174550).