The psychotherapy of dually diagnosed patients.
A model of psychotherapy with dual diagnosis patients is presented. This therapy is divided into 3 phases: achieving sobriety, maintaining abstinence, and advanced recovery. In each of these phases, dual diagnosis patients require many specialized techniques, which are discussed. After sobriety, psychotherapy is behavioral and supportive. When abstinence is stabilized, then psychodynamic principles can be integrated into an approach that recognizes the role played by potential return to substance abuse. Abstinence is even more critical in dual diagnosis patients than in uncomplicated substance abusers. In advanced recovery, more traditional psychotherapy can be done, particularly in nonpsychotic patients.


The Eating Disorder Inventory in a UK National Health Service Obesity Clinic and its response to modest weight loss.
Using the Eating Disorder Inventory (EDI-2) to identify a normative range in a UK obese population referred to a specialist hospital obesity clinic and to assess the response of the scale to the nonsurgical treatment of obesity. A total of 100 obese (BMI>30) patients attending an obesity clinic completed the EDI-2. In a separate sample, 45 obese patients participated in a dietary weight loss program consisting of an acute (10 weeks) and a long-term (2 year) weight maintenance phase. The EDI-2 was administered at baseline and at the end of the acute weight loss phase. Most obese subjects showed elevated scores for body dissatisfaction (BD), which improved with weight loss. Eight percent had EDI scores suggesting psychological traits central to eating disorders. Most obese subjects do not have a trait central to an eating disorder as defined by the EDI-2, but do have high scores for BD that respond to weight loss. A few patients show scores suggesting an eating disorder that may benefit from psychological evaluation.


Mitochondrial function, zinc, and intermediary metabolism relationships in normal prostate and prostate cancer.
Human prostate secretory epithelial cells have the uniquely specialized function of accumulating and secreting extremely high levels of citrate. This is achieved by their ability to accumulate high cellular levels of zinc that inhibit citrate oxidation. This process of net citrate production requires unique metabolic/bioenergetic mitochondrial relationships. In prostate cancer, the malignant cells undergo a metabolic transformation from zinc-accumulating citrate-producing sane cells to citrate-oxidizing malignant cells that lost the ability to accumulate zinc. This review describes the metabolic/bioenergetic, zinc and mitochondrial relationships involved in normal and malignant prostate. Hopefully, this report will generate much needed interest and research in this neglected, but critically important, area of investigation.


Cardiac MRI-based right-to-left ventricular blood pool T2 relaxation times ratio correlates with exercise capacity in patients with chronic heart failure.
MRI T2 mapping has been proven to be sensitive to the level of blood oxygenation. We hypothesized that impaired exercise capacity in chronic heart failure is associated with a greater difference between right (RV) to left ventricular (LV) blood pool T2 relaxation times due to a higher level of peripheral blood desaturation, compared to patients with preserved exercise capacity and to healthy controls. Patients with chronic heart failure (n = 70) who had undergone both cardiac MRI (CMR) and a 6-min walk test (6MWT) were retrospectively identified. Propensity score matched healthy individuals (n = 35) served as control group. CMR analyses included cine acquisitions and T2 mapping to obtain blood pool T2 relaxation times of the RV and LV. Following common practice, age- and gender-adjusted nominal distances and respective percentiles were calculated for the 6MWT. The relationship between the RV/LV T2 blood pool ratio and the results from 6MWT were evaluated by Spearman's correlation coefficients and regression analyses. Inter-group differences were assessed by independent t-tests and univariate analysis of variance. The RV/LV T2 ratio moderately correlated with the percentiles of nominal distances in the 6MWT (r = 0.66) while ejection fraction, end-diastolic and end-systolic volumes showed no correlation (r = 0.09, 0.07 and - 0.01, respectively). In addition, there were significant differences in the RV/LV T2 ratio between patients with and without significant post-exercise dyspnea (p = 0.001). Regression analyses showed that RV/LV T2 ratio was an independent predictor of the distance walked and the presence of post-exercise dyspnea (p < 0.001). The proposed RV/LV T2 ratio, obtained by two simple measurements on a routinely acquired four-chamber T2 map, was superior to established parameters of cardiac function to predict exercise capacity and the presence of post-exercise dyspnea in patients with chronic heart failure.


Metal-enhanced fluorescence detection and degradation of tetracycline by silver nanoparticle-encapsulated halloysite nano-lumen.
The ultrasensitive detection and efficient degradation of tetracycline (TC) residues are important for improving food safety and protecting human health. In this paper, a smart silver-enhanced fluorescence platform for the ultrasensitive detection of TC was constructed via a simple and selective modification of the interior and external tubes of natural halloysite nanotubes. The thick pipe wall of this platform provides a natural defense and promotes metal-enhanced fluorescence effects, which subsequently accelerates the detection of TC. Moreover, the nanoplatform of the modified Ag nanoparticles can induce the separation of electrons and holes, thereby enhancing photocatalytic activity in TC degradation. This platform provides new opportunities for studying natural halloysite nanotubes and for simultaneously detecting and photodegrading other deleterious substances.


Machine learning in medicine: a practical introduction to techniques for data pre-processing, hyperparameter tuning, and model comparison.
There is growing enthusiasm for the application of machine learning (ML) and artificial intelligence (AI) techniques to clinical research and practice. However, instructions on how to develop robust high-quality ML and AI in medicine are scarce. In this paper, we provide a practical example of techniques that facilitate the development of high-quality ML systems including data pre-processing, hyperparameter tuning, and model comparison using open-source software and data. We used open-source software and a publicly available dataset to train and validate multiple ML models to classify breast masses into benign or malignant using mammography image features and patient age. We compared algorithm predictions to the ground truth of histopathologic evaluation. We provide step-by-step instructions with accompanying code lines. Performance of the five algorithms at classifying breast masses as benign or malignant based on mammography image features and patient age was statistically equivalent (P > 0.05). Area under the receiver operating characteristics curve (AUROC) for the logistic regression with elastic net penalty was 0.89 (95% CI 0.85 - 0.94), for the Extreme Gradient Boosting Tree 0.88 (95% CI 0.83 - 0.93), for the Multivariate Adaptive Regression Spline algorithm 0.88 (95% CI 0.83 - 0.93), for the Support Vector Machine 0.89 (95% CI 0.84 - 0.93), and for the neural network 0.89 (95% CI 0.84 - 0.93). Our paper allows clinicians and medical researchers who are interested in using ML algorithms to understand and recreate the elements of a comprehensive ML analysis. Following our instructions may help to improve model generalizability and reproducibility in medical ML studies.


Bone morphogenetic protein activities are enhanced by 3',5'-cyclic adenosine monophosphate through suppression of Smad6 expression in osteoprogenitor cells.
Bone morphogenetic proteins (BMPs) belong to the transforming growth factor (TGF)-beta superfamily, and some display potent osteogenic activity both in vivo and in vitro. The BMP signaling cascade involving BMP receptors at the cell membrane and intracellular messengers (Smads) has been elucidated, but the regulatory mechanisms of BMP signaling have not been clarified. We previously found that pentoxifyline (PeTx), a nonspecific inhibitor of phosphodiesterase (PDE), and rolipram, a PDE-4-specific inhibitor, enhance BMP-4-induced osteogenic differentiation of mesenchymal cells, probably through the elevation of intracellular cyclic adenosine monophosphate (cAMP) accumulation and modulation of BMP signaling pathways as enhanced BMP-4 action was reproduced by addition of dibutylyl-cAMP (dbcAMP). However, the precise mechanisms underlying the enhancing effects of those agents on BMP signaling were not completely revealed. As already reported, BMPs utilize a specific intracellular signaling cascade to target genes via R-Smads (Smad1,5,8), Co-Smad (Smad4) and I-Smads (Smad6,7). One possibility for cAMP-mediated effects on BMP signaling might be suppression of I-Smads expression since these proteins form a negative feedback loop in BMP signaling. To examine this possibility, changes in I-Smad (Smad6) expression on addition of dbcAMP or PeTx were examined in a bone-marrow-derived osteogenic cell line (ST2). Alkaline phosphatase activity in ST2 cells was consistently induced by BMP-4 treatment (300 ng/ml), and Smad6 mRNA expression was also induced by BMP-4 treatment. Although concurrent treatment of ST2 cells with BMP-4 and dbcAMP elicited further activation of alkaline phosphatase, addition of dbcAMP reduced BMP-4-induced Smad6 expression in a dose-dependent manner. Furthermore, detection of phosphorylated Smad1/5/8 on Western blotting analysis was prolonged, suggesting prolonged kinase activity of BMP receptors through suppressed expression of Smad6. Elevated intracellular cAMP might thus enhance BMP signaling by suppressing Smad6 induction and prolonging intracellular BMP signaling.


An analysis of radiological research publications in high impact general medical journals between 1996 and 2010.
To evaluate scientific papers published by radiologists in high impact general medical journals between 1996 and 2010. A MEDLINE search was performed in five high impact general medical journals (AIM, BMJ, JAMA, Lancet, and NEJM) for all articles of which a radiologist was the first author between 1996 and 2010. The following information was abstracted from the original articles: radiological subspecialty, imaging technique used, type of research, sample size, study design, statistical analysis, study outcome, declared funding, number of authors, collaboration, and country of the first author. Of 216 (0.19%) articles were published by radiologists in five general medical journals between 1996 and 2010, 83 were original articles. Fifteen (18.1%) original articles were concerned with the field of vascular/interventional radiology, 24 (28.9%) used combined imaging techniques, 76 (91.6%) were clinical research, 63 (75.9%) had a sample size of >50, 65 (78.3%) were prospective, 78 (94.0%) performed statistical analysis, 83 (100%) showed positive study outcomes, 57 (68.7%) were funded, 49 (59.0%) had from four to seven authors, and 79 (95.2%) were collaborative studies. A very small number (0.19%) in five high impact general medical journals was published by radiologists between 1996 and 2010.


Urokinase-type plasminogen activator receptor is required for impairing toll-like receptor 7 signaling on macrophage efferocytosis in lupus.
The accumulation of apoptotic cells is one of the pathological characteristics of systemic lupus erythematosus (SLE). The expression of urokinase-type plasminogen activator receptor (uPAR) has been reported to be increased in SLE patients and to be involved in macrophage efferocytosis. Although the toll-like receptor 7 (TLR7) is also over-expressed in lupus, its relationship to uPAR and its role in macrophage efferocytosis in lupus is still unclear. In the present study, we revealed that apoptotic cells accumulate in the spleen, macrophage efferocytosis is impaired, and uPAR is increased in the spleen and peritoneal macrophages of the TLR7 agonist imiquimod (IMQ)-induced SLE mouse model. Moreover, TLR7 upregulated uPAR expression in the mouse macrophage RAW 264.7 cells in vitro. The same results were also obtained using peritoneal macrophages of female Balb/c mice. When uPAR levels in peritoneal macrophages were knocked down by siRNA or inhibited by the peptide inhibitor UPARANT, and cells further treated with the TLR7 agonist R848, efferocytosis of peritoneal macrophages on apoptotic cells was restored. These results indicated that TLR7 activation impaired efferocytosis via uPAR in mouse peritoneal macrophages. Furthermore, TLR7 regulated uPAR expression via ERK/JNK signaling in macrophages. These results suggest that uPAR may be an important factor related to the accumulation of apoptotic cells in SLE.


Identification of trehalose-6-phosphate synthase (TPS)-coding genes involved in flowering induction of Lilium× formolongi.
Lilium × formolongi, a facultative long-day (LD) plant, can complete the floral transition within one year after sowing under LD conditions. In addition to the photoperiod, the molecular mechanisms by which other flowering regulators, such as sugar, participate in juvenile development and flowering induction in L. × formolongi remain elusive. Therefore, based on the investigation of seedling development under different day length conditions, we explored the growth and nonstructural carbohydrate (NSC) contents of leaves and underground bulbs. Furthermore, the expression profiles of trehalose-6-phosphate synthase (TPS)-coding genes, LfTPSs, and miR156 were also determined. Three putative LfTPS genes, LfTPS1, LfTPS3 and LfTPS5, displayed high expression levels at the juvenile vegetative stage under different day length conditions. Among them, LfTPS1 maintained gradually elevated expression until the visible bud stage under short-day (SD) conditions. Additionally, the expression levels of LfTPS3 and LfTPS5 increased with the exogenous sucrose concentration. In contrast, the expression of miR156 rapidly decreased under the same sucrose treatments. Overexpression of LfTPS1/3/5 hastened flowering and the decline in miR156 expression levels to varying degrees in transgenic Arabidopsis. Taken together, the results demonstrate that LfTPS1, LfTPS3 and LfTPS5 modulate both juvenile vegetative development and flowering induction controlled by sugars in L. × formolongi.


Hb J Camaguey alpha 2 141(HC3) Arg replaced by Gly beta 2: a new abnormal human hemoglobin.
An electrophoretic fast-moving hemoglobin was found in a Cuban family of Spanish descent. Structural studies demonstrated a replacement of arginine by glycine at alpha 141(HC3). This change is not associated with clinical symptoms, although the substitution is in one of the residues involved in the stabilization of the deoxy form of the hemoglobin molecule.


Molecular characterization of a Penicillium chrysogenum exo-1,5-alpha-L-arabinanase that is structurally distinct from other arabinan-degrading enzymes.
The nucleotide sequence of the abnx cDNA gene, which encodes an exo-arabinanase (Abnx) of Penicillium chrysogenum 31B, was determined. Abnx was found to be structurally distinct from known arabinan-degrading enzymes based on its amino acid sequence and a hydrophobic cluster analysis. The protein in the protein database with the highest similarity to Abnx was the Neurospora crassa conserved hypothetical protein. The abnx cDNA gene product expressed in Escherichia coli catalyzed the release of arabinobiose from alpha-1,5-L-arabinan. The activity of the recombinant Abnx towards a series of arabino-oligosaccharides, as expressed by k(cat)/K(m) value, was greatest with arabinohexaose.


Short term high-intensity interval training in patients scheduled for major abdominal surgery increases aerobic fitness.
Prehabilitation may improve postoperative clinical outcomes among patients undergoing major abdominal surgery. This study evaluated the potential effects of a high-intensity interval training (HIIT) program performed before major abdominal surgery on patients' cardiorespiratory fitness and functional ability (secondary outcomes of pilot trial NCT02953119). Patients were included before surgery to engage in a low-volume HIIT program with 3 sessions per week for 3 weeks. Cardiopulmonary exercise and 6-min walk (6MWT) testing were performed pre- and post-prehabilitation. Fourteen patients completed an average of 8.6 ± 2.2 (mean ± SD) sessions during a period of 27.9 ± 6.1 days. After the program, [Formula: see text]O2 peak (+ 2.4 ml min-1 kg-1, 95% CI 0.8-3.9, p = 0.006), maximal aerobic power (+ 16.8 W, 95% CI 8.2-25.3, p = 0.001), [Formula: see text]O2 at anaerobic threshold (+ 1.2 ml min-1 kg-1, 95%CI 0.4-2.1, p = 0.009) and power at anaerobic threshold (+ 12.4 W, 95%CI 4.8-20, p = 0.004) were improved. These changes were not accompanied by improved functional capacity (6MWT: + 2.6 m, 95% CI (- 19.6) to 24.8, p = 0.800). A short low-volume HIIT program increases cardiorespiratory fitness but not walking capacity in patients scheduled for major abdominal surgery. These results need to be confirmed by larger studies.


Evidence supporting involvement of leukotrienes in LPS-induced hypothermia in mice.
The aim of the present study was to examine a possible involvement of leukotrienes (LTs) in lipopolysaccharide (LPS)-induced body temperature (Tb) response. We examined the effect of MK-886, an inhibitor of LT synthesis, on changes in Tb, plasma tumor necrosis factor-alpha (TNF-alpha), hypothalamic LT, and PGE2 production. Intraperitoneal injection of LPS (50 microgramg/mouse) led to a decrease in Tb starting 1 h after the injection. The hypothermic effect of LPS was accompanied by a significant elevation in TNF-alpha level in plasma and in LT and PGE2 production by ex vivo-incubated hypothalamus. MK-886 (1 mg/kg ip) administered 4 h before LPS efficaciously prevented LPS-induced hypothermia in mice. Pretreatment of mice with MK-886 did not alter the LPS-stimulated increase in plasma TNF-alpha. MK-886 significantly inhibited LT and enhanced PGE2 production in hypothalamus compared with LPS alone. These results suggest that 1) LPS-induced hypothermia may be mediated by LTs and 2) the antihypothermic effect of MK-886 is not associated with TNF-alpha bioactivity.


Validation of a rapid and reliable test for diagnosis of chagas' disease by detection of Trypanosoma cruzi-specific antibodies in blood of donors and patients in Central America.
In this study we compared the performance of the Chagas Stat-Pak rapid immunochromatographic test with a standard enzyme-linked immunosorbent assay (ELISA) in the serodiagnosis of Chagas' disease in Central America. Out of 3,400 blood donor samples, 156 (4.6%) were positive in both assays. Three sera out of 2,084 samples from reference laboratories were negative with the rapid test but positive with the ELISA (99.8% agreement). Agreement of 100% between the two tests was observed with 339 additional sera from patients with cardiopathies and 175 sera from potential blood donors in emergency surgical cases occurring on weekends or at night. In conclusion, Chagas Stat-Pak showed 99.6% and 99.9% sensitivity and specificity, respectively, when assayed with 5,998 serum samples. It is a sensitive and specific alternative to the ELISA, as required in medical emergencies and blood screenings in Central America.


Combined treatment with peroxisome proliferator-activated receptor (PPAR) gamma ligands and gamma radiation induces apoptosis by PPARγ-independent up-regulation of reactive oxygen species-induced deoxyribonucleic acid damage signals in non-small cell lung cancer cells.
To investigate possible radiosensitizing activities of the well-known peroxisome proliferator-activated receptor (PPAR)γ ligand ciglitazone and novel PPARγ ligands CAY10415 and CAY10506 in non-small cell lung cancer (NSCLC) cells. Radiosensitivity was assessed using a clonogenic cell survival assay. To investigate the mechanism underlying PPARγ ligand-induced radiosensitization, the subdiploid cellular DNA fraction was analyzed by flow cytometry. Activation of the caspase pathway by combined PPARγ ligands and γ-radiation treatment was detected by immunoblot analysis. Reactive oxygen species (ROS) were measured using 2,7-dichlorodihydrofluorescein diacetate and flow cytometry. The 3 PPARγ ligands induced cell death and ROS generation in a PPARγ-independent manner, enhanced γ-radiation-induced apoptosis and caspase-3-mediated poly (ADP-ribose) polymerase (PARP) cleavage in vitro. The combined PPARγ ligand/γ-radiation treatment triggered caspase-8 activation, and this initiator caspase played an important role in the combination-induced apoptosis. Peroxisome proliferator-activated receptor-γ ligands may enhance the γ-radiation-induced DNA damage response, possibly by increasing γ-H2AX expression. Moreover, the combination treatment significantly increased ROS generation, and the ROS scavenger N-acetylcysteine inhibited the combined treatment-induced ROS generation and apoptotic cell death. Taken together, these results indicated that the combined treatment of PPARγ ligands and γ-radiation synergistically induced DNA damage and apoptosis, which was regulated by ROS.


The simultaneous use of a heat and moisture exchanger and a heated humidifier causes critical airway occlusion in less than 24 hours.
Heat and moisture exchangers (HMEs) and heated humidifiers (HHs) may be used together inadvertently. Such an incident occurred at our institution resulting in airway occlusion. A bench-top study was conducted to compare the incidence of airway occlusion when using (1) no airway humidification, (2) HME alone, (3) HH alone, and (4) both HME and HH in combination as part of a standard breathing circuit. The simultaneous use of a HME and a HH was associated with a reduction in tidal volume (no airway humidification, P ≤ .05; HME alone, P ≤ .01; and HH alone, P ≤ .01) and an increased incidence of airway occlusion (no airway humidification, 0/7; HME alone, 0/7; HH alone, 0/7; and HME and HH in combination, 7/7; P < .0001). The use of a HME and a HH in combination is likely to result in airway occlusion. Precautions should be taken to ensure that both systems are not used together in clinical practice.


Packing forces in ribonuclease crystals.
Packing in Ribonuclease A and Ribonuclease S crystals have been compared in order to determine the possible role of the precipitant on lattice contacts. Both proteins have similar tertiary structures, but they crystallize in different space groups depending on the precipitating agent. It is found that packing differs either by the number of nearest neighbours or by the size of surface areas buried in individual contacts. Ammonium sulfate seems to promote hydrophobic interactions with interfaces similar to those found in oligomeric proteins. Organic precipitants favour electrostatic interactions.


Family nursing in intensive care. Part two: The needs of a family with a member in intensive care.
It was demonstrated in Part one that the family is a justifiable concern to nurses in intensive care and that family-focused care is appropriate in such an area. If this approach to care is to be considered, it is necessary to identify the needs of families when they have a member in an intensive care unit. This is a well-researched area and some of the relevant literature is discussed within this paper. Before this literature is addressed, an attempt is made to define the concept of need. The methodologies used in the identification of family needs could be adapted to explore whether or not the needs of the families of patients in a particular intensive care unit are being met. This paper suggests that if it was shown that the meeting of family needs was an area of care which could be improved upon, then a family-centred approach to care would be a reasonable option. If however, it is shown that families already perceived their needs as being met, then changing the system of care to a more formal family nursing approach would seem to be unnecessary.


Empirical antimicrobial therapy in pediatric patients with neutropenia and fever. Risk factors for treatment failure.
The use of combinations of antibiotics has been the cornerstone of therapy for febrile patients with cancer and severe neutropenia. Each empirical regimen should be selected according to the epidemiology and susceptibility patterns in each center. We describe here the experience with empirical antimicrobial treatments in pediatric patients with cancer, fever and severe neutropenia, and identify the risk factors associated with treatment failure. This is a prospective study including 145 patients with cancer, and 171 episodes of neutropenia and fever. Blood cultures were taken before initiating empirical treatment: a) carbenicillin (400 mg/kg/day) plus amikacin (21 mg/kg/day) (Cb/ak), and b) ceftazidime (100 mg/kg/day), plus amikacin at the same dosage (Cz/ak). The overall response rate was 54.9% and 56.3% for Cb/ak and Cz/ak, respectively. Fifty-seven episodes (33.3%) were microbiologically documented, gram-positive isolated in 38% and gram-negative in 49%. Risk factors associated significantly with treatment failure were acute myelocytic leukemia (AML) (RR 2.59, CI 95% 1.42-4.7, p = 0.003); bacteriological identification (RR = 4.41, CI 95% 2.21-8.8, p < 0.001), and the presence of two or more sites of infection (RR = 2.89, CI 95% 1.03-8.11, p = 0.03). The rates of response are similar to the combinations used in the hospital (Cb/ak, Cz/ak). The risk factors associated with treatment failure were AML diagnosis, bacteriological identification, and the presence of two or more sites of infection.


Mineralocorticoids, salt balance and blood pressure after prolonged ACTH administration in juvenile hypertension.
The effect of a 5 day ACTH test (40 U/24 h) on plasma aldosterone (aldo), deoxycorticosterone (DOC), plasma renin activity (PRA) and urinary excretion of aldosterone-pH1-conjugate (pH-1-aldo) and tetrahydro-DOC (TH-DOC) was investigated in 8 normotensive children (group I), 8 patients with hypertension of unknown origin (group II), and 4 hypertensive children with dexamethasone suppressible hyperaldosteronism (DSH) (group III). Changes in blood pressure and sodium balance were studied in all groups. Under baseline conditions there was no hormonal difference between group I and II. In contrast, the children in group III had a suppressed PRA and a 1.5--2 fold elevation of aldo and DOC. Plasma DOC and urinary THDOC increased continuously 10--50 fold in all groups during the ACTH test. Aldo rose transiently 2--4 fold on the first day of ACTH and fell subsequently below baseline levels in group I and II. The children with DSH (group III), however, showed an unusual, sustained aldo stimulation with ACTH. PRA decreased significantly after ACTH in group I and II. Sodium retention aTH administration. The highest blood pressure rise was observed in group III (from 124/72 to 139/90 mm Hg). The blood pressure response to ACTH was partly sodium dependent. Although aldo and DOC and sodium retention may contribute to the ACTH induced blood pressure elevation, other factors must play a role.


Boundaries can steer active Janus spheres.
The advent of autonomous self-propulsion has instigated research towards making colloidal machines that can deliver mechanical work in the form of transport, and other functions such as sensing and cleaning. While much progress has been made in the last 10 years on various mechanisms to generate self-propulsion, the ability to steer self-propelled colloidal devices has so far been much more limited. A critical barrier in increasing the impact of such motors is in directing their motion against the Brownian rotation, which randomizes particle orientations. In this context, here we report directed motion of a specific class of catalytic motors when moving in close proximity to solid surfaces. This is achieved through active quenching of their Brownian rotation by constraining it in a rotational well, caused not by equilibrium, but by hydrodynamic effects. We demonstrate how combining these geometric constraints can be utilized to steer these active colloids along arbitrary trajectories.


Purification, some properties and the complete primary structures of two protease inhibitors (DE-3 and DE-4) from Macrotyloma axillare seed.
The Macrotyloma axillare plant, belonging to the Leguminosae family, is a perennial climbing or trailing herb 0.2--3.5 m long. The plant is indigenous to South Africa and it occurs in the warm dry northern parts of the Transvaal. It has been introduced into Australia, where the seed are used as animal food. Two protease inhibitors, DE-3 and DE-4, were purified from Macrotyloma axillare seed by gel filtration on Sephadex G-50 followed by ion-exchange chromatography on DEAE-cellulose. They each comprise 76 amino acid residues including 14 half-cystine residues. The complete primary structures of the two protease innibitors have been elucidated and their sequences are 67% identical. The inhibitor specificities, the sequences, the invariant amino acid residues and the reactive inhibitor sites of protease inhibitors DE-3 and DE-4 resemble the corresponding properties of the Bowman-Birk double-headed protease inhibitor group. The cysteine residues are in similar locations to those in protease inhibitors of known structure so they are presumed to link similarly.


Tomatidine targets ATF4-dependent signaling and induces ferroptosis to limit pancreatic cancer progression.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with high metastasis and therapeutic resistance. Activating transcription factor 4 (ATF4), a master regulator of cellular stress, is exploited by cancer cells to survive. Prior research and data reported provide evidence that high ATF4 expression correlates with worse overall survival in PDAC. Tomatidine, a natural steroidal alkaloid, is associated with inhibition of ATF4 signaling in multiple diseases. Here, we discovered that in vitro and in vivo tomatidine treatment of PDAC cells inhibits tumor growth. Tomatidine inhibited nuclear translocation of ATF4 and reduced the transcriptional binding of ATF4 with downstream promoters. Tomatidine enhanced gemcitabine chemosensitivity in 3D ECM-hydrogels and in vivo. Tomatidine treatment was associated with induction of ferroptosis signaling validated by increased lipid peroxidation, mitochondrial biogenesis, and decreased GPX4 expression in PDAC cells. This study highlights a possible therapeutic approach utilizing a plant-derived metabolite, tomatidine, to target ATF4 activity in PDAC.


Rapid and selective determination of UV filters in seawater by liquid chromatography-tandem mass spectrometry combined with stir bar sorptive extraction.
Fast liquid chromatography coupled to triple-quadrupole tandem mass spectrometry was employed for the determination of six UV filters in seawater. The separation of the analytes was achieved in less than 5 min; polarity switching was used as four of the analytes were ionized in positive mode and the remaining two in negative mode. Two ionization sources were employed and compared: atmospheric pressure chemical ionization (APCI) gave better results than electrospray ionization (ESI) for all analytes, with higher reproducibility and lower detection limits. Therefore APCI was chosen for the determination of the analytes in seawater samples using stir bar sorptive extraction-liquid desorption (SBSE-LD). Quantitative analysis was performed in multiple reaction monitoring (MRM) mode; fragmentation pathways of the analytes with regard to the formation of the MRM ions were also proposed. For the analysis of seawater samples, calibration curves were drawn using SBSE in spiked seawater. All figures of merit of the method were satisfactory; limits of detection were particularly low for the four analytes ionized in positive mode, being in the range 8-31 ng/L. The method was applied to the determination of the six UV filters in seawater samples from Liguria, Italy. Only benzophenone-3 (BP-3) and ethylhexyl methoxycinnamate (EHMC) were measured in the analyzed samples; some of the remaining analytes were also detected but always below the limit of quantitation.


Role of endogenous melatoninergic system in development of hyperalgesia and tolerance induced by chronic morphine administration in rats.
Morphine is a widely used analgesic for various types of pain. However, its efficacy is impeded by development of hyperalgesia and tolerance. Melatonin has antinociceptive effect and is involved in morphine-induced hyperalgesia and tolerance but the mechanism of its involvement remains to be defined. In this study, we established a rat model of morphine-induced hyperalgesia and tolerance. We determined the serum level of melatonin and expression of μ-opioid receptor (MOR), melatonin receptor (MT1, MT2) and protein kinase C γ(PKCγ) in the spinal dorsal horn of the rats with morphine-induced hyperalgesia and tolerance. Comparing with control group (n=6), the group (n=6) of rats with morphine-induced hyperalgesia and tolerance exhibited a significant lower serum melatonin level, reduction in expression of the MT1, but up-regulation of the PKCγ in the spinal dorsal horn. These results may facilitate revealing the mechanism of opioid-induced hyperalgesia and tolerance and exploring new therapeutic remedy for pain management.


Germination and establishment of Sahelian rangeland species : I. Seed properties.
In the context of a study on the dynamics of Sahelian rangelands, seed characteristics of about 30 species have been described, with particular attention to germination characteristics. Data on both form and weight of the seeds are presented. Germination was studied under controlled conditions in a climate room. Optimum conditions for germination were established, and the species were characterized by induction time, slope of germination vs. time curve and final germination percentage. The results obtained under climate room conditions appear to be correlated satisfactorily with the behaviour of the different species in the field.


Techniques to Study Common Root Responses to Beneficial Microbes and Iron Deficiency.
Iron (Fe) plays a central role in the vital processes of a plant. The Fe status of a plant influences growth and immunity, but it also dictates interactions of roots with soil microbiota through the production of Fe mobilizing, antimicrobial fluorescent phenolic compounds called coumarins. To adapt to low Fe availability in the soil, plants deploy an efficient Fe deficiency response. Interestingly, this Fe deficiency response is hijacked by root-colonizing microbes in the root microbiome to establish a mutually beneficial relationship. In this chapter, we describe how we cultivate plants and microbes to study the interaction between plants, beneficial rhizobacteria, and the plant's Fe deficiency response. We describe (a) how we study activity and localization of these responses by assessing gene-specific promoter activities using GUS assays, (b) how we visualize root-secreted coumarins in response to Fe deficiency and colonization by beneficial rhizobacteria, and (c) how we prepare our samples for metabolite extraction and reverse-transcriptase quantitative PCR to analyze the expression of marker genes.


Effects of histamine bolus injections and continuous infusions on the H1- and H2-receptors in the hindlimb vessels of the rabbit.
1. Hindlimb vascular resistance (HVR) was continuously measured after pharmacological block of the autonomic effectors in unanesthetized rabbits with previously implanted Doppler ultrasonic flowmeters. 2. Histamine bolus injections caused a dose-related short lived fall in HVR followed by a more sustained rise. The fall was due to H2-receptor stimulation (blocked by burimamide or metiamide) and the rise to H1-receptor stimulation (blocked by mepyramine). At the doses of histamine tested the magnitude of the H1-mediated vasoconstriction had a larger peak effect than the H2-mediated vasodilatation. 3. Histamine infusions up to 200 microgram kg-1 min-1 did not alter HVR significantly but both increases and decreases in HVR were observed after giving H2- or H1-antagonists, respectively. 4. From the double reciprocal plots of 1/peak HVR change and 1/dose of histamine the magnitude of the predicted H1- and H2-mediated peak HVR effects at large doses were the same. This suggested that the number of H1- and H2-receptors were similar in the hindlimb vascular bed, in agreement with the infusion data.


Analytic processing in the classification of melodies as same or different.
Two groups of non-musicians were required to classify pairs of melodies as "same" or "different". The experimental group was instructed to respond as fast as possible, while the control group did not receive such a speed requirement. Contrary to the control subjects, the experimental subjects exhibited a right-ear advantage in accuracy for "different" responses. Thus, time pressure was instrumental in inducing subjects to rely mainly on left-hemisphere processing. The fact that "different" responses were both faster than "same" ones and quicker than melody offset indicates the use of a self-terminating search process. The features searched for were, in all likelihood, local. Indeed, contrary to control subjects, experimental subjects performed equally well with (1) melodies differing in both contour and local pitches and with (2) melodies differing in local pitches only.


Determination of benzophenones in river-water samples using drop-based liquid phase microextraction coupled with gas chromatography/mass spectrometry.
In this study, a fast, simple and highly sensitive method that employs liquid phase microextraction (LPME)-GC/MS was developed to analyze trace benzophenones (BPs) in river-water samples. The tip of a 10-microl microsyringe filled with toluene (3 microl) was inserted into 2 ml of a river-water sample, and fixed at 5 mm below the water surface of the sample. A toluene droplet was made on the tip of the syringe, and extraction was conducted while agitating at 500 rpm for 15 min. After extraction, 2.0 microl of the extract was put into the syringe again, and directly introduced to GC/MS. The limits of detection (S/N = 3) and quantification (S/N >10) of BPs were 10 and 50 pg ml(-1), respectively. The results of a recovery test ranged over 93.3 - 101.1% (RSD, less than 10%; n = 6). The results of BPs determinations in the river-water samples showed that BPs (ND - 68.9 pg ml(-1)) were detected.


Surface properties of endosseous dental implants after NdYAG and CO2 laser treatment at various energies.
Dental lasers have been used for uncovering submerged implants as well as decontaminating implant surfaces when treating peri-implantitis. The objective of this study was to compare the possible alterations of the smooth surface and resorbable blast material (RBM) surface implants after using NdYAG and CO(2) lasers at various energies. Ten smooth surface implants and 10 RBM surface implants were used. Two smooth surface implants and 2 RBM surface implants served as a control group that was not lased. The remaining implants were treated using NdYAG and CO(2) lasers. The surface of each implant was treated for 10 seconds on the second and third threads. The smooth surface implants (group 1) were treated using a pulsed contact NdYAG laser at power settings of 1, 2, 3.5, and 5 W, which are commonly used for soft tissue surgery; the corresponding energy and frequency were 50 mJ and 20 Hz, 100 mJ and 20 Hz, 350 mJ and 10 Hz, and 250 mJ and 20 Hz, respectively. The group 2 RBM implants were treated using a pulsed contact NdYAG laser. The group 3 smooth surface implants were treated using a pulsed wave non-contact CO(2) laser at 1, 2, 3.5, and 5 W, and the group 4 RBM implants were treated using a pulsed wave non-contact CO(2) laser. Data were analyzed using scanning electron microscopy. The control surface was very regular and smooth. After NdYAG laser treatment, the implant surface showed alterations of all the surfaces. The amount of damage was proportional to the power. A remarkable finding was the similarity of the lased areas on the smooth and RBM surfaces. CO(2) laser at power settings of 1.0 or 2.0 W did not alter the implant surface, regardless of implant type. At settings of 3.5 and 5 W, there was destruction of the micromachined groove and gas formation. This study supports that CO(2) laser treatment appears more useful than NdYAG laser treatment and CO(2) laser does not damage titanium implant surface, which should be of value when uncovering submerged implants and treating peri-implantitis.


Selective inhibition of NF-kappaB activation by the flavonoid hepatoprotector silymarin in HepG2. Evidence for different activating pathways.
The bioflavonoid silymarin is found to potently suppress both nuclear factor kappa-B (NF-kappaB)-DNA binding activity and its dependent gene expression induced by okadaic acid in the hepatoma cell line HepG2. Surprisingly, tumor necrosis factor-alpha-induced NF-kappaB activation was not affected by silymarin, thus demonstrating a pathway-dependent inhibition by silymarin. Many genes encoding the proteins of the hepatic acute phase response are under the control of the transcription factor NF-kappaB, a key regulator in the inflammatory and immune reactions. Thus, the inhibitory effect of silymarin on NF-kappaB activation could be involved in its hepatoprotective property.


Effects of hydrolyzed gallotannin on intestinal physical barrier, immune function, and microbiota structure of yellow-feather broilers.
The present study was performed to explore the effects of dietary supplementation of hydrolyzed gallotannin (HGT) on intestinal physical barrier, immune function and microbiota structure in yellow-feather broilers. A total of 288 male yellow-feather broilers were randomly allocated to 4 diet treatments: the basal diet (CON) and 3 diets supplemented with 150, 300, and 450 mg/kg HGT for 63 d, respectively, with 6 replicates per treatment and 12 birds per replicate. The findings demonstrated that 300 or 450 mg/kg HGT addition enhanced the expression of duodenal occludin (OCLN) and tight junction protein1 (TJP-1) genes of birds at 21 d of age, and the expression of duodenal and ileal OCLN gene in 63-day-old broilers was upregulated due to 450 mg/kg HGT treatment (P < 0.05). The dietary supplementation of 150 mg/kg HGT strengthened the expression of duodenal IL-6 and IL-4 genes and ileal IL-4 gene of 21-day-old broilers, whereas the expression of jejunal IL1B and IL-6 genes in birds at 63 d of age weakened because of 300 or 450 mg/kg HGT addition (P < 0.05). As for microbial community, the HGT addition altered the cecal microbiota structure of birds at 21 d of age based on analysis of similarities (ANOSIM) test and 450 mg/kg HGT treatment increased the relative abundance of norank Eubacterium coprostanoligenes group at 21 d of age and unclassified Lachnospiraceae at 63 d of age (P < 0.05). In short, diet supplemented with 300 to 450 mg/kg HGT may be the optimal for yellow-feather broilers to enhance intestinal barrier function. Altogether, our study clarified the regulatory role of HGT in broiler intestinal health in earnest, but the underlying mechanism is still unclear. Hence, more research is needed to carry out until the application of HGT as a new functional additive in broiler production.


New nitroindazole-porphyrin conjugates: Synthesis, characterization and antibacterial properties.
The synthesis of new porphyrin-indazole hybrids by a Knoevenagel condensation of 2-formyl-5,10,15,20-tetraphenylporphyrin and N-methyl-nitroindazolylacetonitrile derivatives is reported. The target compounds were isolated in moderate to good yields (32-57%) and some of the isolated porphyrin-indazole conjugates showed good performance in the generation of singlet oxygen when irradiated with visible light. Their efficiency as photosensitizers in the photoinactivation of methicillin resistant Staphylococcus aureus-MRSA was evaluated. All derivatives showed to be able to photoinactivate the MRSA bacteria. Compound 3a appears to be the most promising photosensitiser (PS) in the photoinactivation of these bacteria, despite being the least efficient in singlet oxygen generation. The addition of potassium iodide (KI) significantly potentiated the antimicrobial Photodynamic Therapy (aPDT) process mediated by all the analysed porphyrin-indazole conjugates. The combined action of nitroindazole-porphyrins with potassium iodide (KI) action appears to be promising in the photoinactivation of MRSA.


Rain, prey and predators: climatically driven shifts in frog abundance modify reproductive allometry in a tropical snake.
To predict the impacts of climate change on animal populations, we need long-term data sets on the effects of annual climatic variation on the demographic traits (growth, survival, reproductive output) that determine population viability. One frequent complication is that fecundity also depends upon maternal body size, a trait that often spans a wide range within a single population. During an eight-year field study, we measured annual variation in weather conditions, frog abundance and snake reproduction on a floodplain in the Australian wet-dry tropics. Frog numbers varied considerably from year to year, and were highest in years with hotter wetter conditions during the monsoonal season ("wet season"). Mean maternal body sizes, egg sizes and post-partum maternal body conditions of frog-eating snakes (keelback, Tropidonophis mairii, Colubridae) showed no significant annual variation over this period, but mean clutch sizes were higher in years with higher prey abundance. Larger females were more sensitive to frog abundance in this respect than were smaller conspecifics, so that the rate at which fecundity increased with body size varied among years, and was highest when prey availability was greatest. Thus, the link between female body size and reproductive output varied among years, with climatic factors modifying the relative reproductive rates of larger (older) versus smaller (younger) animals within the keelback population.


Self-administered behavior modification to reduce nail biting: incorporating simple technology to ensure treatment integrity.
Habitual behaviors, such as problematic nail biting, are a common target for self-managed behavior-modification programs. The current self-experiment used self-monitoring in conjunction with a self-managed differential-reinforcement procedure for the treatment of problematic nail biting. A simple picture-comparison procedure allowed an independent observer to assist in monitoring treatment progress and outcomes and to ensure treatment integrity. Results provide support that the overall treatment package was successful in decreasing the occurrence of nail biting. Moreover, the treatment-integrity procedure enabled full-day monitoring to take place with limited requirement of a secondary observer.


Heavy metal poisoning resistance of a Co-modified 3Mn10Fe/Ni low-temperature SCR deNOx catalyst.
Heavy metals have a great influence on the deNOx efficiency of catalysts. The 3Mn10Fe/Ni catalyst that used nickel foam (Ni) as the carrier, Mn and Fe as the active components, and Co as a trace auxiliary was prepared using an impregnation method. The catalysts poisoned by Pb or Zn and Co-modified catalysts with Pb or Zn poisoning were studied. The addition of Pb or Zn significantly decreases the deNOx activity of the 3Mn10Fe/Ni catalyst due to the decrease in the content of high-valence metal elements such as Fe3+ and Mn4+, lattice oxygen concentration, reduction performance, acidity, and the number of acid sites. However, after Co modification, the deNOx activity of the poisoned catalysts can be improved effectively because the strong interaction between Pb or Zn and lattice oxygen is weakened, and the contents of lattice oxygen, high valence metal elements, reduction ability, and the number of acid sites increase.


The prevalence of human papillomavirus in squamous cell carcinoma of unknown primary site metastatic to neck lymph nodes: a systematic review.
A subset of head and neck squamous cell carcinoma, which mainly arise from the crypt epithelium of the palatine and lingual tonsils, may be caused by high-risk human papillomavirus (HPV) infections. This topographical restriction together with other overlapping clinical features have led investigators to suspect that HPV plays a role in squamous cell carcinoma of unknown primary (SCCUP) site metastatic to neck lymph nodes. We performed a systematic review of articles listed in PubMed to identify studies testing HPV and/or p16(INK4a) status (p16) in tissue samples from initial and definitive SCCUP. The prevalence of HPV-related (HPV DNA-positive and/or p16 positive) SCCUP was calculated for all the SCCUP, initial SCCUP, suspected definitive SCCUP, and true definitive SCCUP whenever a minimum of 10 cases of each category was identified. In addition, data concerning patients' diagnostic work-up, the HPV detection methods, and the correlations between HPV-status, the localization of the occult primary tumor, and the clinical outcome were also extracted. Eighteen retrospective cohort studies, assessing a total of 659 patients, met the inclusion criteria. The overall median prevalences of HPV-DNA(pos), of p16(pos), and of positivity for both HPV markers were, respectively, 37.0, 48.5, and 36.0 %. Patients with diagnosis of initial SCCUP had overall median prevalences of HPV-DNA(pos), of p16(pos), and of positivity for both HPV markers, respectively, of 81.8, 86.2, and 80.8 %. The data uncovered by this systematic review confirm that SCCUP is frequently causally associated to HPV-driven oropharyngeal squamous cell carcinomas. This finding supports the view that HPV-status could be routinely assessed in SCCUP patients as it may lead to identifying the primary tumor and the decision to de-escalate treatment.


Retrograde ejaculation caused by incomplete paralysis of pelvic nerve.
A case of retrograde ejaculation is reported. Initially, it was considered idiopathic, but various examinations revealed subclinical neurogenic bladder with hypotonic detrusor and normal external urethral sphincter. This was due to incomplete paralysis of the pelvic nerve and the normal activity of the pudendal nerve. Normal antegrade ejaculation was obtained by bilateral pudendal nerve block. Some cases of idiopathic retrograde ejaculation are ascribable to neurogenic bladder; and urodynamic examination is essential in the diagnosis of this disease.


Does a weight-training exercise programme given to patients four or more years after total knee arthroplasty improve mobility: A randomized controlled trial.
To investigate the effects of the home exercise therapy performed after at least four years postoperatively on skeletal muscle strength and functionality in patients with total knee arthroplasty (TKA). Sixty patients (age; 69.66±7.53, weight; 81.56±14.43 kg, 10 male, 50 female) followed up four or more years were randomly divided into two groups. An 8-week exercise program was designed for bilateral TKA patients. While the patients in one group were assigned to weighted exercise group, the patients in the other group were assigned to non-weighted exercise group. The primary outcome was the isometric muscle strength of quadriceps femoris (QF) and hamstring muscles assessed by Hand-Held Dynamometer. The secondary outcomes were the pain level, 30s sit-to-stand test, 10 m walk test, range of motion, and the knee function score of the Hospital for Special Surgery. The assessments were performed before and after the treatment. After treatment, significant differences were found in all evaluation parameters (except rest pain and range of motion) in favour of the weighted group. QF muscle strength changes (kg); weighted group: 1.99±1.70, non-weighted group: 0.51±1.14 (p=0.000), 30s sit-to-stand test changes (repetitions); weighted group: 3.66±2.23, non-weighted group: 1.70±1.95 (p=0.000), 10 m walk test changes (seconds); weighted group: -2.60±1.30, non-weighted group: -0.83±3.51 (p=0.000). Home exercise programs applied to TKA patients after at least four years postoperatively was effective in increasing muscle strength, decreasing severity of pain, and improving functional activities. The improvements were significantly greater in weighted compared with the non-weighted exercise group.


Acetyl-L-carnitine and α-lipoic acid affect rotenone-induced damage in nigral dopaminergic neurons of rat brain, implication for Parkinson's disease therapy.
Although the mechanisms of neurodegeneration in Parkinson's disease are not fully understood, mitochondrial dysfunction, oxidative stress and environmental toxins may be involved. The current research was directed to investigate the protective role of two bioenergetic antioxidants, acetyl-L-carnitine and α-lipoic acid, in rotenone-parkinsonian rats. Ninety six male rats were divided into five groups. Group I is the vehicle-injected group, group II is the disease control group and was injected with six doses of rotenone (1.5 mg/kg/48 h, s.c.). Groups III, IV and V received rotenone in addition to acetyl-L-carnitine (100 mg/kg/day, p.o.), α-lipoic acid (50 mg/kg/day, p.o.) or their combination, respectively. Results showed that rotenone-treated rats exhibited bradykinesia and motor impairment in the open-field and square bridge tests. In addition, ATP level was decreased whereas lipid peroxides and protein carbonyls increased in the striata of rotenone-treated rats as compared to vehicle-treated rats. Treatment with acetyl-L-carnitine or α-lipoic acid improved the motor performance and reduced the level of lipid peroxides in rat brains as compared to rotenone group. Further, ATP production was enhanced along with acetyl-L-carnitine treatments (p≤0.05). Taken together, our study reinforces the view that acetyl-L-carnitine and α-lipoic acid are promising candidates for neuroprotection in Parkinson's disease.


Effects of intraventricular injection of 6-hydroxydopamine in the developing kitten. 1. On the sleepwaking cycles.
Intraventricular 6-OHDA was injected in kittens at different stages of development, and the subsequent sleep polygram was analyzed, in order to determine the role of the catecholaminergic system in the ontogenesis of sleep regulations during the first and the second postnatal months. 6-OHDA, used with or without previous chlorimipramine treatment, led within a 10-day period to drastic reductions of the endogenous monoamines in the forebrain of all age groups. Although the neurotoxicity of 6-OHDA was almost constant among the different age groups, the effects on sleep depended on the age of the animals at the time of the injection. In the 5-week-old injected kittens, 6-OHDA affected PS according to an adult-like pattern. In the 3-week-old kittens, 6-OHDA alone (leading to both catecholamines and serotonin decreases) induced the same PS deficit as in the adult cat. In the 1- and 2-week-old kittens, neither 6-OHDA alone, nor 6-OHDA with previous chlorimipramine treatment, distrubed the sleep regulations. These data are compared to similar experiments performed in the adult cat. They are discussed in terms of sleep control ontogenesis. It is concluded that the catecholaminergic system plays no important role in the mechanisms of sleep regulation in the early postnatal period in the kitten, whereas its regulatory influence on PS is confirmed in the juvenile animal. The functional maturation of the catecholaminergic system in terms of sleep regulation is achieved between the third and the fifth week of postnatal life.


Role of cardiovascular echo in patients with Takayasu arteritis.
Takayasu arteritis is an important differential diagnosis in young female patients presenting with fever, fatigue, hypertension, and/or neck pain. Aortic arch branch vessels are frequently affected and the carotid artery can have diffuse, homogeneous wall thickening, known as the 'macaroni sign'. The descending aorta can be stenotic with 'pseudo-coarctation'. Cardiovascular echo plays an important role in the screening and characterization of arterial lesions in patients with Takayasu arteritis.


Abnormalities in position of left ventricular papillary muscles in congenital aortic stenosis.
Subclinical structural abnormalities may accompany some congenital cardiovascular abnormalities. Echocardiographic observations led us to hypothesize that the positions of the left ventricular papillary muscles are abnormal in hearts with aortic valvar stenosis. To test this hypothesis, we examined 6 normal heart specimens and hearts with congenital cardiovascular malformations, including 5 with pulmonary atresia and an intact ventricular septum, 6 with tetralogy of Fallot and 5 with aortic valvar stenosis. We marked the papillary muscles and the mitral commissures, X-rayed the hearts, and measured the angular positions of the papillary muscles using the midpoint of a chord drawn between the mitral commissures as a reference point. The direction from the midpoint to the lateral commissure was designated as 0 degrees. The data (mean +/- SEM) were analyzed using a computer program (ANOVA). In normal hearts, the anterolateral and posteromedial papillary muscles were positioned, respectively, at 43 +/- 19 degrees and 126 +/- 26 degrees. The positions of the papillary muscles were similar to normal in the hearts with pulmonary atresia (62 +/- 38 degrees and 128 +/- 27 degrees) and tetralogy of Fallot (40 +/- 13 degrees and 130 +/- 37 degrees). In aortic stenosis, the locations of the papillary muscles (-76 +/- 42 degrees and 71 +/- 25 degrees) were significantly different from normal (P less than 0.05). The arc between the papillary muscles was 83 +/- 16 degrees in normals and 147 +/- 45 degrees in aortic stenosis (P less than 0.05). The length of the arc was similar to normal in other heart specimens. Thus, the papillary muscles were abnormally positioned in aortic stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)


A Linear Dose-Response Relationship between Fasting Plasma Glucose and Colorectal Cancer Risk: Systematic Review and Meta-analysis.
For many years, the question of whether hyperglycaemia, a manifestation of prediabetes, diabetes mellitus and metabolic syndrome, is a risk factor for colorectal cancer has been intensely studied. In fact, even after the conclusion of several prospective studies, the topic is still controversial. We conducted a systematic review and meta-analysis to investigate the dose-response relationship between blood glucose concentration and the incidence of colorectal cancer. A linear (P = 0.303 for non-linearity) dose-response relationship was observed between fasting plasma glucose (FPG) and colorectal cancer risk without significant heterogeneity. The relative risk (RR) for colorectal cancer per 20 mg/dL increase in FPG was 1.015 (95% CI: 1.012-1.019, P = 0.000). In subgroup analyses, the pooled RRs for colon cancer (CC) and rectal cancer (RC) studies were 1.035 (95% CI 1.008-1.062, P = 0.011) and 1.031 (95% CI: 0.189-5.628, P = 0.972), respectively; in the analysis comparing men and women, the pooled RRs were 1.016 (95% CI: 1.012-1.020, P = 0.000) and 1.011 (95% CI: 0.995-1.027, P = 0.164), respectively. Sensitivity analyses using two methods showed similar results. In conclusion, there is a significant linear dose-response relationship between FPG and the incidence risk of colorectal cancer. For people with diabetes or prediabetes, controlling blood glucose might be useful to prevent colorectal cancer.


The effect of remote health intervention based on internet or mobile communication network on hypertension patients: Protocol for a systematic review and meta-analysis of randomized controlled trials.
To systematically review the impact of remote health interventions based on an internet or mobile communication network on patients with hypertension and to provide a theoretical basis for hypertension patients with the implementation of remote health interventions. Data were retrieved from a total of 4 Chinese databases and 3 foreign databases. The Chinese databases included: China National Knowledge Infrastructure (CNKI), WanFang Data, Chinese Biomedical Database (SinoMed), and Chongqing Chinese Science and Technology Journey database (VIP). The foreign language databases included PubMed, The Cochrane Library, and EMbase, and the date range for the search was from the date the database became active to December 1, 2018. After screening and extracting the materials and evaluating the risk of bias in each study (conducted by 2 researchers), the quality of the selected literature was evaluated by Review Manager (RevMan) [Computer program]. Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014, and the statistical analysis was applied by Stata 12.0 software. This study will provide high-quality evidence-based medicine research evidence for remote health interventions on hypertensive patients based on the Internet and mobile communication network using systematic evaluation and meta-analysis methods. This systematic review will provide a scientific conclusion as to whether the remote health intervention model based on an internet or mobile communication network can better control blood pressure and improve patient compliance than the traditional nursing intervention model for hypertensive patients. This protocol for a systematic review and meta-analysis of randomized controlled trials does not require ethical approval and the results of this paper will be published in an open form in internationally influential academic journals. A protocol had been registered in PROSPERO CRD42019122404.


Recombinant human thrombomodulin in the treatment of acute myeloid leukemia patients complicated by disseminated intravascular coagulation: retrospective analysis of outcomes between patients treated with heparin and recombinant human thrombomodulin therapy.
Recombinant thrombomodulin (rTM) is a promising anticoagulant. Improvements in disseminated intravascular coagulation (DIC) and the amelioration of bleeding complications in DIC patients were reported to be greater with rTM therapy than with unfractionated heparin therapy. However, it remains unknown whether rTM therapy affects the outcomes of patients with acute myeloblastic leukemia (AML). We retrospectively analyzed 103 patients with AML and compared outcomes between patients treated with low molecular weight heparin therapy and rTM. The diagnostic criteria for DIC were previously proposed by the Japanese Ministry of Health and Welfare. Comparisons between qualitative variables were carried out using the χ(2) test. Survival probabilities were estimated by the Kaplan-Meier method, and differences in survival distributions were evaluated using the log-rank test. Forty-seven patients developed DIC due to chemotherapy or their disease status. Fourteen patients were treated with rTM, while 33 patients were treated with low-molecular-weight heparin (LMWH). The log-rank test revealed that overall survival was significantly worse in the DIC group than in the non-DIC group (P=0.003), and was signfiacntly better in the rTM group than the LMWH group (P=0.016). rTM was more efficient than LMWH because of the improvements it induced in overall survival.


The spectrum of symptomatic arterialized developmental venous anomalies: case reports.
Developmental venous anomaly (DVA) is an anatomical variation of the intracranial venous system, usually without clinical repercussion. In most cases, DVAs are incidentally diagnosed and should be considered as benign conditions. In rare circumstances, DVAs may become symptomatic due to mechanical or flow-related etiologies. The authors present three cases of symptomatic arterialized DVAs: a 28-year-old male with hematoma at the splenium of the corpus callosum and intraventricular hemorrhage, a 53-year-old male patient with a history of epileptic seizures starting recently, and a 25-year-old male patient, previously healthy who started with persistent headaches and hemosiderin deposition in brain parenchyma. These rare cases of arterialized DVAs are conditions that can cause symptoms or show more aggressive behavior with bleeding.


High-risk Stage III colon cancer patients identified by a novel five-gene mutational signature are characterized by upregulation of IL-23A and gut bacterial translocation of the tumor microenvironment.
The heterogeneities of colorectal cancer (CRC) lead to staging inadequately of patients' prognosis. Here, we performed a prognostic analysis based on the tumor mutational profile and explored the characteristics of the high-risk tumors. We sequenced 338 colorectal carcinomas as the training dataset, constructed a novel five-gene (SMAD4, MUC16, COL6A3, FLG and LRP1B) prognostic signature, and validated it in an independent dataset from The Cancer Genome Atlas (TCGA). Kaplan-Meier and Cox regression analyses confirmed that the five-gene signature is an independent predictor of recurrence and prognosis in patients with Stage III colon cancer. The mutant signature translated to an increased risk of death (hazard ratio = 2.45, 95% confidence interval = 1.15-5.22, p = 0.016 in our dataset; hazard ratio = 4.78, 95% confidence interval = 1.33-17.16, p = 0.008 in TCGA dataset). RNA and bacterial 16S rRNA sequencing of high-risk tumors indicated that mutations of the five-gene signature may lead to intestinal barrier integrity, translocation of gut bacteria and deregulation of immune response and extracellular related genes. The high-risk tumors overexpressed IL23A and IL1RN genes and enriched with cancer-related bacteria (Bacteroides fragilis,Peptostreptococcus, Parvimonas, Alloprevotella and Gemella) compared to the low-risk tumors. The signature identified the high-risk group characterized by gut bacterial translocation and upregulation of interleukins of the tumor microenvironment, which was worth further researching.


Cloning of Aspergillus nidulans ribosomal DNA in shotgun experiments using the EK2 vector lambda gtWEST.T5-622.
EcoRI fragments of Aspergillus nidulans DNA were cloned in a shotgun type experiment using the EK2 vector lambda gtWEST.T5-622. In situ plaque hybridization was used to screen for hybrid phage particles containing sequences coding for ribosomal RNA. Four clones selected from the whole gene bank were characterized further. Two of them contain sequences homologous to a 3.6 Kb fragment of A. nidulans rDNA.


Recent developments in corticoid synthesis.
In an attempt to improve the industrial manufacture of corticoids starting from desoxycholic acid, two major tasks had to be accomplished: (1) selective transposition of a 12 alpha-oxygen function to the 11-position. (2) Degradation of the side chain by three carbon atoms. The most convenient solution to the first problem included protection of the 3 alpha-hydroxyl, then dehydrating the 12 alpha-alcohol via its mesylate, and treatment of the resulting delta 11-12-alkene with PDC and iodine, to obtain the 12 alpha-iodo-11-ketone in very high yield. After reductive dehalogenation and saponification, the resulting acid proved to be suitable for solving our second problem. Oxidative decarboxylation with lead tetraacetate leads to an olefin, the double bond of which could be shifted along the side chain to produce the corresponding delta 20-22-isomer. Ozonolytic cleavage of the C--C double bond in this position made the 20-ketone 19 readily accessible. The latter plays a key role in the production of various corticoid drugs, since most of them are derived from this very compound, e.g. cortisol.


Chromosomal variants in mentally retarded and normal men.
The possible phenotypic effect of chromosomal variants is as yet an unsolved problem. QM- and C-banded chromosomes of 100 male patients with idiopathic mental retardation were compared with chromosomes of 100 Royal Military College cadets, as controls. Increased size of 9qh seems to be a factor with possible negative effects. 9qh- was found to be more common in the control sample. Another variant found more often in the retarded subjects was 16qh-. Increased frequencies of Yq+ or small inversions in chromosomes 3 and 9 were not found in the retarded.


Abuse potential of zomepirac.
Zomepirac sodium, a nonsteroidal anti-inflammatory analgesic, was compared to morphine sulfate and placebo in an abuse liability study in a postaddiction population. Morphine (15 and 30 mg), but not zomepirac (400 and 800 mg), induced pupillary constriction and characteristic morphinelike subjective effects. The 800-mg dose of zomepirac was discriminated but was not euphorigenic. This study indicates that zomepirac is not likely to be abused.


Peroneal Artery Adipofascial Flaps for Coverage of Distal Leg and Rearfoot.
Chronic wounds of the lower extremity can pose several obstacles for the treating physician as well as the patient. Peroneal artery adipofascial flaps have been shown to be a reliable and durable option for reconstruction of these defects for many reasons, including ease of dissection, minimized donor site mobility, reliability of take to underlying surfaces, and cosmetically more pleasing outcome. This article discusses the current literature regarding the use of peroneal artery adipofascial flaps and our surgical technique for harvest, transfer, and postoperative course for this versatile flap.


Autobiographical memory specificity and restrained eating: examining the influence of priming with images of healthy and unhealthy foods.
Dietary restraint has been linked to deficits in the ability to recall detailed memories of personally experienced events (referred to as autobiographical memory specificity). As priming with healthy foods increases the salience of restraint it would be expected to lead to greater deficits in memory specificity. To determine if priming word cues with images of healthy or unhealthy foods would influence the specificity of memory retrieval, and if deficits in memory specificity would be more evident in those reporting higher levels of dietary restraint, or currently dieting. Sixty female undergraduates self-reported if they were currently dieting and completed measures of mood, restraint, and disinhibition, and a modified version of the autobiographical memory task. Participants were presented with positive and negative words (unrelated to eating concerns) and asked to retrieve a specific memory in response to each cue. A food image was shown prior to each word cue; half of the participants were primed with images of healthy foods and half with images of unhealthy foods. As expected, participants primed with healthy foods retrieved fewer specific memories than did those primed with unhealthy foods. However, neither restraint nor current dieting behaviour was associated with memory specificity. Differences in memory specificity between the priming conditions cannot be explained in terms of increased salience of restraint. However, it is plausible that unhealthy images led to an increase in positive affect, which in turn improved memory specificity. Level I: Evidence obtained from: at least one properly designed experimental study.


Physicochemical properties and in vitro digestibility of proso millet starch after addition of Proanthocyanidins.
The solubility and swelling power, pasting, structure, and digestibility properties of proso millet starch (PMS) with different concentration of proanthocyanidins (PA) were investigated. The results showed that with PA content increasing, the solubility and swelling power of starch increased, the PA accelerated the water absorption and expansion of starch. The results of pasting properties showed that PA increased the peak viscosity of starch, but decreased the setback and pasting temperature. A significant decrease in enthalpy value was measured by differential scanning calorimetry, the enthalpy value decreased from 14.98 J/g to 10.24 J/g at 20% PA concentration. The relative crystallinity of starch, as well as the ratio at 1049/1022 cm-1, decreased due to the increasing PA concentration, indicating the ordered degree of starch reduced, while the hydrogen bonding in the system was enhanced by PA. The addition of PA decreased the RDS content of uncooked and cooked starch, the RS content increased. When the PA concentration was 20%, the RS content was 1.05 and 1.92 times for native starch, respectively, which significantly reduced the starch digestibility.


Memory retention: potentiation of cholinergic drug combinations in mice.
The amnesias characteristic of Alzheimer's disease and other age-related dementias are refractory to conventional pharmacotherapy. A recent strategy is to combine present drugs, to improve their memory enhancing effect. We utilize mice weakly trained on active avoidance in a T-maze in order to compare the effect on retention test performance of cholinergic drugs given alone and in two-drug and three-drug combinations. All drugs were injected intraventricularly immediately after training. Memory retention was tested one week later. A dose-response curve was determined for each of four drugs (arecoline, edrophonium, oxotremorine, deanol) and for several of their fixed-ratio combinations. The results indicate that each drug and each combination improved retention test performance up to an optimal dose; the improvement decreased with further increases in dose. A striking reduction (as much as 95%) in the optimal dose for enhanced retention was observed with these two-drug combinations, and further reduction with a three-drug combination. The practical implications of planned drug interactions as an improved means of treating amnesias associated with aging are under investigation.


Determination of the required HLB values of some essential oils.
The required HLB values of eucalyptus, lippia and peppermint essential oils were determined using droplet size analysis and turbidimetric method on emulsions prepared with emulsifier blends of varying HLB values. The percentage increase in mean droplet diameter and the degree of dispersion of droplet sizes were determined before and after centrifugation of the emulsions. The HLB value of the emulsion with the least dispersion ratio or the least percentage increase in mean droplet diameter was taken as the required HLB of the respective essential oil. The turbidimetric method was validated by the existence of correlation (r=-0.958) between the mean droplet diameter and the turbidity of the emulsions. The turbidity curve went through a maximum at the HLB value where the mean droplet diameter was least. Based on these methods, the required HLB values of eucalyptus, lippia and peppermint oils were determined as 9.8, 12.1 and 12.3, respectively (P<0.05). Liquid paraffin was used as a reference standard and its required HLB fell within literature value.


Noninvasive evaluation of carotid artery stenosis: indications, strategies, and accuracy.
Carotid artery occlusive disease is an important stroke risk factor and accounts for a significant proportion of stroke morbidity and mortality. In this article we survey the major clinical trials related to stroke risk in symptomatic and asymptomatic patients who have internal carotid artery (ICA) stenosis; techniques for noninvasive screening of ICA stenosis including ultrasound, MR angiography, and CT angiography; and evolving algorithms for ICA evaluation. We comment on current interest in plaque morphology as a risk factor for stroke.


Effect of chronic treatment with SCH 23390 and haloperidol on spontaneous activity of dopamine neurones in substantia nigra pars compacta (SNC) and ventral tegmental area (VTA) in rats.
The effect of chronic treatment (21 days s.c.) with SCH 23390 and haloperidol on spontaneously active DA neurones in substantia nigra pars compacta (SNC) and ventral tegmental area (VTA) was studied in rats by means of single unit recording techniques. The specific DA D-1 receptor antagonist SCH 23390 was injected twice daily in one of the following doses: 0.06, 0.23, 0.46 or 0.90 mumol/kg. SCH 23390 decreased the number of spontaneously active neurones in SNC and VTA to the same extent. The DA D-2 receptor antagonist haloperidol was injected once daily in one of the following doses: 0.05, 0.21 or 1.7 mumol/kg and induced a decrease in the number of spontaneously active DA neurones in SNC and VTA. These results suggest that SCH 23390 has a profile similar to that of haloperidol and that SCH 23390 has clinical antipsychotic activity but also induces extrapyramidal side-effects.


A toxicological study on photo-degradation products of environmental ibuprofen: Ecological and human health implications.
Increasing quantities of pharmaceutical waste in the environment have disrupted the balance of ecosystems, and may have subsequent effects on human health. Although a handful of previous studies have shown the impacts of pharmaceutically active compounds on the environment, the toxicological effects of their degradation products remain largely unknown. In the current study, the photo-degradation products of environmental ibuprofen were assessed for both ecotoxicological and human health effects using a series of in vitro assays. Here, six of the major degradation products are synthesized with high purity (>98%) and characterized with 1HNMR, 13CNMR, FT-IR and HRMS. To evaluate human health effects, three gut microbiota species, Lactobacillus acidophilus, Enterococcus faecalis and Escherichia coli, and two human cell lines, HEK293T and HepG2, are exposed to various concentrations of ibuprofen and its degradation products. On L. acidophilus, the ibuprofen degradation product (±)-(2R,3R)-2-(4-isobutylphenyl)-5-methylhexan-3-ol shows a greater toxic effect while ibuprofen enhances its growth at lower concentrations. At higher concentrations, ibuprofen shows at least a 2-fold higher toxicity compared to that of its degradation products. However, E. faecalis shows little or no effect upon exposure to these compounds. An induction of the SOS response in E. coli is observed but limited to only ibuprofen and 4-acetylbenzoic acid. In human cell line studies, survival of both HEK293T and HepG2 cell lines is profoundly impaired by the photo-degradation products of (±)- (2R,3R)-2-(4-isobutylphenyl)-5-methylhexan-3-ol, (±)-(2R,3S)-2-(4-isobutylphenyl)-5-methylhexan-3-ol, and (±)-1-(4-(1-hydroxy-2methylpropyl)phenyl)ethan-1-one. In this work, the bioluminescence bacterium, Aliivibrio fischeri, is used as a model to assess environmental impact. Both ibuprofen and its degradation products inhibit the growth of this gram-negative bacteria with the primary compound showing the most significant impact. Overall, our results highlight that some of the degradation products of ibuprofen can be more toxic to human kidney cell line and liver cell line than the parent compound while ibuprofen can be more toxic to human gut microbiota and A. fischeri than ibuprofen degradation products.


Comparison of Interaction between Ceruloplasmin and Lactoferrin/Transferrin: to Bind or Not to Bind.
The year 2016 marked the 50th anniversary of the discovery by S. Osaki who first showed that ceruloplasmin (CP, ferro:O2-oxidoreductase or ferroxidase) is capable of oxidizing Fe(II) to Fe(III) and favors the incorporation of the latter into transferrin (TF). However, much debate remains in the literature concerning the existence of a complex between the enzyme oxidizing iron and the protein facilitating its transport in plasma. We studied CP in exocrine fluids and demonstrated its high-affinity interaction with transferrin found in breast milk and in lacrimal fluid, i.e. with lactoferrin (LF). Here we present data obtained by comparing the interaction of CP with LF and TF using surface plasmon resonance and Hummel-Dreyer chromatography. Binding of apo-LF within the range of concentrations 1.6-51.3 µM with CP immobilized on a CM5-chip is characterized by KD = 1.07 µM. Under similar conditions, the KD for apo-TF was measured and appeared to be higher than 51.3 µM. Hummel-Dreyer chromatography of CP with 51 µM apo-LF/apo-TF in the effluent demonstrated the absence of interaction between apo-TF and CP in solution, contrary to efficient interaction between apo-LF and CP. In contrast to LF, the interaction of apo-TF with CP is probably not stable within the physiological range of concentrations of TF.


Protein synthesis by pure translation systems.
We have developed a partially recombinant, cell-free, protein-synthesis system reconstituted solely from those essential elements of the Escherichia coli translation system, termed protein synthesis using recombinant elements (PURE). It provides higher reaction controllability in comparison to crude cell-free protein-synthesis systems for translation studies and biotechnology applications. The PURE system stands out among translation methods in that it provides not only a simple and unique "reverse" purification method of separating the synthesized protein from reaction mixture, but also that the system can be tailor-made according to individual protein requirements. In this paper, two new approaches to obtaining active proteins are described: the use of molecular chaperones, and modification of the reaction conditions. Several possible applications of the PURE system are also discussed.


Genetic Predisposition to Drug-Induced Liver Injury.
Identification of genetic predisposition to drug-induced liver injury (DILI) is of paramount importance. Early candidate gene studies have identified various polymorphisms in drug-metabolizing genes that infer increased DILI susceptibility. Few of these have been confirmed in more recent genome-wide association studies, which have identified several specific human leukocyte antigen (HLA) alleles. The low incidence rate of DILI, however, leads to a low positive predictive value for currently identified genetic variations, making them unsuitable for pre-prescription screening. HLA screening incorporated into clinical practice can aid the diagnostic process resulting in enhanced diagnostic accuracy and confidence.


Clinical Efficacy of a Combination of Thymopentin and Antituberculosis Drugs in Treating Drug-Resistant Pulmonary Tuberculosis: Meta Analysis.
To make a systematic evaluation of the clinical efficacy of thymopentin combined with antituberculous drugs in treating drug-resistant pulmonary TB (PTB). Relevant studies were retrieved from PubMed, Embase, Cochrane Library, Chinese Biomedical Literature Database, CNKI, and Wanfang Database. STATA software was used to evaluate the differences in focal absorption rate, the time to cough symptom remission, sputum culture-negative rate, CD3+ T, CD4+ T, and CD8+ T cell levels after treatment. A total of 23 randomized controlled trials literature involving 2031 cases were included. Meta-analysis revealed that compared with conventional therapy, the sputum culture-negative rate was significantly increased after 2-3 months and 6-9 months of treatment and the whole course of combined thymopentin treatment. The risk ratio (RR, 95% CI) was 1.44 (1.26-1.64), 1.47 (1.21-1.78), and 1.27 (1.18-1.36), respectively. In the combined thymopentin treatment group, the focal absorption rate was higher, with RR (95% CI) = 1.36 (1.25-1.47), the time of cough remission was shortened, with WMD (95% CI) =-9.46d (-10.36,-8.57) and the differences were all statistically significant. Combined thymopentin therapy could effectively improve the levels of CD3+ T and CD4+ T lymphocytes in patients with drug-resistant PTB after 2-3 months, 6-9 months of treatment. The WMD (95% CI) were 9.96% (7.84, 12.08), 4.68% (2.90, 6.47) and 10.26% (7.81, 12.71), 7.21% (6.28, 8.15), respectively, and could also reduce the level of CD8+ T lymphocytes after 2-3 months and 6-9 months of treatment. The WMD (95% CI) were -4.06% (-4.96, -3.13), -3.52%, (-4.07,-2.98), respectively, and the differences were all statistically significant. Thymopentin adjuvant treatment for drug-resistant PTB can promote the therapeutic effect and improve the immune indexes in patients with drug-resistant PTB.


Anatomical Description of Anterior Parametrium: A Probable Answer to Pelvic Recurrence Following Radical Hysterectomy.
A prospective analysis of a retrospective data of patients with cervix carcinoma treated by minimal invasive surgery at high-volume gynecology oncology center analyzing that minimal access surgery is an acceptable treatment modality in cervix carcinoma. The study included 423 patients who underwent laparoscopic/robotic radical hysterectomy after pre-operative evaluation after taking their consent and obtaining ethical approval from the IRB. Post-operatively, patients were followed up at regular intervals for clinical examination and ultrasonography for a median range of 36 months. A PET scan was done only if there was any suspicious finding on clinical examination or ultrasonography. Patients with parametrial involvement, positive vaginal margins, and nodal involvement were treated with chemotherapy/radiotherapy. Four hundred twenty-three patients of cervix carcinoma were treated with minimal access surgery. Average duration of surgeries was 92 min. Median range of duration of post-operative follow-up was 36 months. None of the patients had positive resection margins indicating adequate parametrectomy with complete oncological clearance. On post-operative follow-up, only 2 patients had vaginal recurrence which is comparable to that observed in open surgery and no pelvic recurrence. With the understanding of the anatomical landmarks of the anterior parametrium and development of skills for adequate oncological clearance, minimal access surgery should be the preferred surgical modality in carcinoma of the cervix.


Morphology of cortically projecting basal forebrain neurons in the rat as revealed by intracellular iontophoresis of horseradish peroxidase.
The intracellular horseradish peroxidase technique was employed to study the morphology of basal forebrain neurons that were identified as cortically projecting by antidromic invasion from the cerebral cortex. Four neurons were examined in detail; they were located at different rostrocaudal levels within the basal forebrain. Their somata were large, 30-50 microns in longest dimension, and gave rise to three to eight primary dendrites, which ramified into third- to fifth-order dendrites. The longest observed dendrite in each neuron terminated at a distance of 600-900 microns from the soma. The sizes of soma and dendritic field of the two most rostrally located cells were smaller than those of the other two cells located more caudally. Dendritic spines were seen in all four cortically projecting basal forebrain neurons. Spines had shafts of variable lengths, and usually had spherical or elongated heads. The density of spines varied among the four neurons; one neuron, a type II cortically projecting basal forebrain neurons as defined physiologically by Reiner et al., had a much greater number of dendritic spines than the other three neurons, which were type I neurons. No somatic spines were observed. Presumptive axons were identified in three of the four cortically projecting basal forebrain neurons. These axons originated from either the soma or a primary dendrite, and two of them gave off local collaterals, which displayed occasional bouton-like swellings. The above observations confirm and extend previous findings that cortically projecting neurons in the basal forebrain are large multipolar cells, and provide evidence to support the conclusion that these cells, although somewhat variable in size, generally have extensive dendrites which display frequent spines.


Medical Weight Optimization for Arthroplasty Patients: A Primer of Emerging Therapies for the Joint Arthroplasty Surgeon.
The obesity epidemic in the United States continues to grow with more than 40% of individuals now classified as obese (body mass index >30). Obesity has been readily demonstrated to increase the risk of developing hip and knee osteoarthritis and is known to increase the risk of complications following joint arthroplasty. Weight loss prior to arthroplasty may mitigate this risk of complications; however, the existing evidence remains mixed with no clear consensus on the optimal method of weight loss and timing prior to arthroplasty. Treatment options for weight loss have included nonsurgical lifestyle modifications consisting of structured diet, physical activity, and behavioral modification, as well as bariatric and metabolic surgery (ie, sleeve gastrectomy, Roux-en-Y gastric bypass, and the adjustable gastric band). Recently, glucagon-like peptide-1 receptor agonists have gained notable popularity within the scientific literature and media for their efficacy in weight loss. The aim of this review is to provide a foundational primer for joint arthroplasty surgeons regarding the current and emerging options for weight loss to aid surgeons in shared decision-making with patients prior to arthroplasty.


Polish validation of the University of Washington "quality of life" questionnaire in patients with cancer of the larynx.
The University of Washington Quality of Life questionnaire version 4 (UW-QoLv4), in English, is used worldwide to assess the quality of life in patients with head and neck cancer. The use of such a questionnaire in other languages requires translation and validation in that language, and our aim was to translate it into Polish (which we did) and validate it in a group of patients diagnosed with head and neck cancer who had been considered free of disease for at least six months during routine follow-up visits to the Lower Silesian Oncology Center, Wrocław. Using the Polish version of the questionnaire, 66 patients filled in the translated version of UW-QoLv4 and the European Organization for Research and Treatment of Cancer (EORTC) questionnaires, which were compared and analysed. Results showed good reliability, which was confirmed by internal consistency (Cronbach's' α=0.765-0.809). The construct validity was confirmed, with strong relations between the UW-QoLv4 and the EORTC scale (p<0.05). We conclude that the Polish version of the UW-QoLv4 questionnaire seems to have been translated well, is valid, and is valuable for the assessment of quality of life among Polish patients with cancers of the head and neck.


Enhanced heme accessibility in horse heart mini-myoglobin: Insights from molecular modelling and reactivity studies.
Mini-myoglobin (mini-HHMb) is a fragment of horse-heart myoglobin (HHMb) considered to be the prototype of the product encoded by the central exon of the HHMb gene. For this reason, mini-HHMb has been studied extensively showing that carbonylation and oxygenation properties of the ferrous form are similar to those of the full-length protein, while kinetics and thermodynamics of azide binding to the ferric form are significantly different from those of HHMb. To analyze the structure-function relationships in mini-HHMb and the role of conformational fluctuations in ligand accessibility, the molecular model of mini-HHMb has been built and refined by molecular dynamics simulations, and analyzed in parallel with that of full length HHMb. Moreover, imidazole binding parameters of ferric mini-HHMb and HHMb have been determined. Furthermore, structural data of ferric mini-HHMb and HHMb have been correlated with the imidazole and previously determined azide binding properties. Present results indicate that, despite the extensive trimming, the heme-α-helices E-F substructure is essentially unaltered in mini-HHMb with respect to HHMb. However, the heme-Fe atom displays an enhanced accessibility in mini-HHMb, which may affect both ligand association and dissociation kinetics.


Distinct mechanisms of T cell reconstitution can be identified by estimating thymic volume in adult HIV-1 disease.
We have attempted to identify factors associated with T cell reconstitution in response to highly active antiretroviral therapy. In a prospective, multicenter cohort study, we compared clinical, immune, and viral responses to an initial antiretroviral regimen in older (>or=45 years old) versus younger (18-30 years old) human immunodeficiency virus type 1-infected subjects. Multivariable linear-regression models identified independent factors associated with changes in T cell counts. Older subjects had smaller increases in naive T cells but greater T cell receptor-excision circle DNA content after 48 weeks, despite similar virologic responses and comparable reductions in immune activation. Changes in T cell counts were associated with plasma interleukin (IL)-7 levels in subjects with low thymic scores, whereas first-phase T cell increases (perhaps mediated by redistribution to the circulation of tissue-associated lymphocytes) were associated with reductions in immune activation in subjects with high thymic scores. Reductions in immune activation were associated with reductions in spontaneous lymphocyte apoptosis. Distinct processes may underlie T cell restoration, according to estimated thymic volumes. IL-7-mediated peripheral expansion may drive T cell restoration in persons with low thymic volume, whereas therapy-associated reversal of immune reactivation may drive T cell losses and their restoration in persons with larger thymic volume.


[Opinion survey on the use of personal health records in the Region of Murcia (Spain)].
To identify the opinions of patients of the Murcia Health Service on the adoption of personal health records (PHRs) and the factors associated with these opinions. A cross sectional and descriptive study was performed by personal survey of a sample of individuals (N=156) aged between 14 and 80 years old in five public health facilities of districts VI and VII of the Health Service of Murcia. A total of 87.8% of the population stated they would use PHRs. Respondents aged 24-33 years old were 13.15 times more willing to use PHRs (95% CI: 1.09-157.42) than people over 63 years old. A lower probability of using PHRs was found in people who did not use the Internet, with an odds ratio of 0.31 (95% CI: 0.07-1.29); this difference was not statistically significant. Most of the patients surveyed had never heard of PHRs but most would be willing to use them.


Reliability of a simple method for determining muscle fiber conduction velocity.
This study evaluated the reliability of muscle fiber conduction velocity (MFCV) measurement. Forty healthy, young participants performed isometric dorsiflexion of the foot on 3 non-consecutive days. The reliability of force, root-mean-square (RMS) amplitude of the surface electromyographic (sEMG) signal, and MFCV were evaluated using the intraclass correlational analysis of variance technique. The means across test days for all measures exhibited slight changes (<5%) and were considered stable. All measures exhibited remarkable consistency within subjects as indicated by high intraclass correlation coefficients (0.83-0.98). The procedures resulted in highly reliable MFCV values, and included: (1) electric identification of motor points prior to electrode placement; (2) twitch identification of muscle fiber orientation to guide initial electrode placement; (3) rotation of electrodes clockwise or counter-clockwise to maximize the similarity and delay of compound muscle action potentials across all detection surfaces; and (4) minimization of synergistic activity during voluntary contractions.


Novel Synthetic Opioids: The Pathologist's Point of View.
New Psychoactive Substances (NPS) constitute a broad range of hundreds of natural and synthetic drugs, including synthetic opioids, synthetic cannabinoids, synthetic cathinones, and other NPS classes, which were not controlled from 1961 to 1971 by the United Nations drug control conventions. Among these, synthetic opioids represent a major threat to public health. A literature search was carried out using public databases (such as PubMed, Google Scholar, and Scopus) to survey fentanyl-, fentanyl analogs-, and other synthetic opioid-related deaths. Keywords including "fentanyl", "fentanyl analogs", "death", "overdose", "intoxication", "synthetic opioids", "Novel Psychoactive Substances", "MT-45", "AH-7921", and "U-47700" were used for the inquiry. From our literature examination, we inferred the frequent implication of fentanyls and synthetic opioids in side effects, which primarily affected the central nervous system and the cardiovascular and pulmonary systems. The data showed a great variety of substances and lethal concentrations. Multidrug-related deaths appeared very common, in most reported cases. The investigation of the contribution of novel synthetic opioid intoxication to death should be based on a multidisciplinary approach aimed at framing each case and directing the investigation towards targeted toxicological analyses.


Malnutrition and visceral obesity predicted adverse short-term and long-term outcomes in patients undergoing proctectomy for rectal cancer.
To the best of our knowledge, no previous studies have explored the relationship between visceral obesity and malnutrition. Therefore, this study has aimed to investigate the association between them in patients with rectal cancer. Patients with rectal cancer who underwent proctectomy were included. Malnutrition was defined according to the Global Leadership Initiative on Malnutrition (GLIM). Visceral obesity was measured using computed tomography (CT). The patients were classified into four groups according to the presence of malnutrition or visceral obesity. Univariate and multivariate logistic regression analyses were performed to evaluate risk factors for postoperative complications. Univariate and multivariate cox regression analyses were performed to evaluate the risk factors for overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier survival curves and log-rank tests were performed for the four groups. This study enrolled 624 patients. 204 (32.7%) patients were included in the well-nourished non-visceral obesity (WN) group, 264 (42.3%) patients were included in the well-nourished visceral obesity (WO) group, 114 (18.3%) patients were included in the malnourished non-visceral obesity (MN) group, and 42 (6.7%) patients were included in the malnourished visceral obesity (MO) group. In the multivariate logistic regression analysis, the Charlson comorbidity index (CCI), MN, and MO were associated with postoperative complications. In the multivariate cox regression analysis, age, American Society of Anesthesiologists (ASA) score, tumor differentiation, tumor node metastasis (TNM), and MO were associated with worsened OS and CSS. This study demonstrated that the combination of visceral obesity and malnutrition resulted in higher postoperative complication and mortality rates and was a good indicator of poor prognosis in patients with rectal cancer.