One-pot preparation of conductive composite containing boronic acid derivative for non-enzymatic glucose detection.
The composite consisting of poly(azure A), gold nanoparticles and 4-mercaptophenylboronic acid (PAA-AuNPs-MPBA) was prepared on the glassy carbon electrode surface by using a one-pot electropolymerization protocol. The generation of poly(azure A) film, the reduction of HAuCl4 and the binding of MPBA on metallic gold were simultaneously achieved in the cyclic voltammetric scan process, which was verified by scanning electron microscopy, Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy measurements. MPBA on the composite could capture glucose based on the specific boronic acid-diol binding and form a stable 5-membered cyclic boronate ester, which prevented the penetration and the charge transfer of the ferri-/ferrocyanide couple on the electrode surface. The peak-current change was found to be proportional to the logarithm of the glucose concentration in the range 10nM-10μM with a detection limit of 4nM. The proposed sensor exhibited good immunity from interference of several physiological compounds, reliable reproducibility and satisfying stability and it was successfully used in the determination of glucose in human serum sample.


Arabidopsis Sar1 isoforms play redundant roles in female gametophytic development.
Functional loss of Arabidopsis Sar1b with that of either Sar1a or Sar1c inhibits mitosis of functional megaspores, leading to defective embryo sac formation and reduced fertility. Vesicular trafficking among diverse endomembrane compartments is critical for eukaryotic cells. Anterograde trafficking from endoplasmic reticulum (ER) to the Golgi apparatus is mediated by coat protein complex II (COPII) vesicles. Among five cytosolic components of COPII, secretion-associated Ras-related GTPase 1 (Sar1) mediates the assembly and disassembly of the COPII coat. Five genes in Arabidopsis encode Sar1 isoforms, whose different cargo specificities and redundancy were both reported. We show here that Arabidopsis Sar1a, Sar1b, and Sar1c mediate the development of female gametophytes (FGs), in which Sar1b plays a major role, whereas Sar1a and Sar1c play a minor role. We determined that female transmission of sar1a;sar1b or sar1c;sar1b was significantly reduced due to defective mitosis of functional megaspores. Half of ovules in sar1a;sar1b/+ or sar1c;sar1b/+ plants failed to attract pollen tubes, leading to fertilization failure. The homozygous sar1a;sar1b or sar1c;sar1b double mutant was obtained by introducing either UBQ10:GFP-Sar1b or UBQ10:GFP-Sar1c, supporting their redundant function in FG development.


Effect of Donor- and Recipient-Related Factors on Arterial Resistance Index After Kidney Transplant.
The assessment of color Doppler resistance index (RI) of the intra-renal arteries has been shown to be a good predictor of short-term and long-term graft survival after kidney transplant. In this study, we investigated the influence of donor- and recipient-related factors on RI evaluated early after kidney transplant. We prospectively analyzed 90 kidney transplant patients who underwent RI assessment within the first month after the transplant, subdivided into 2 groups according their RI values lower (group A) or higher (group B) than 0.646 (median value). Patients in group A had a lower human leukocyte antigen (HLA) mismatch number (3.3 ± 1 versus 3.9 ± 0.9, P = .007) and were significantly younger (42.8 ± 11 years versus 47.8 ± 11 years, P = .03) than patients in group B. All the others variables examined were not significantly different between the 2 groups. Multivariate logistic regression analysis confirmed that HLA mismatch number (P = .03) and recipient age (P = .03) are independent predictors of RI. Our data suggest that HLA mismatches and donor age can influence recipient kidney vascular resistance in the early period after transplantation.


Fenugreek seed powder protects mice against arsenic-induced neurobehavioral changes.
The current study was designed to evaluate the protective effect of fenugreek seed powder against As-induced neurobehavioral and biochemical perturbations using a mouse model. Mice exposed to arsenic at 10 mg/kg body weight showed development of anxiety-like behavior and memory impairment compared to control mice in elevated plus maze and Morris water maze tests, respectively. A significantly decreased acetyl and butyrylcholinesterase, superoxide dismutase and glutathione reductase activities and brain-derived neurotrophic factor levels were found in the brain of arsenic-exposed mice compared to control mice. Interestingly, supplementation of fenugreek seed powder to arsenic-treated mice significantly restored the activity of cholinesterase and antioxidant enzymes (e.g. superoxide dismutase, glutathione reductase) as well as brain-derived neurotrophic factor levels in the brain tissue of arsenic-exposed mice. Consequently, reduced anxiety-like behavior, improved learning and memory were observed in fenugreek supplemented arsenic treated mice compared to only arsenic-exposed mice group. Thus, this study suggests that fenugreek seed powder reduces arsenic-induced neurotoxicity in mice.


Examination of antigenic proteins of Trypanosoma cruzi to fabricate an epitope-based subunit vaccine by exploiting epitope mapping mechanism.
Chagas disease is a protozoan parasitic disease caused by Trypanosoma cruzi. This injurious disease spread by the circulation of the blood sucking triatomine insects and transmitted to humans. Chagas disease is endemic in Latin America and also known as American trypanosomasis. Currently, 7 million people are infected by T. cruzi infection and about 22,000 death cases were reported per year throughout the Americas. Various immunization approaches against T. cruzi infection have been examined and some of the developed vaccine showed efficacy in animal models but there is no effective and safe vaccines for humans have been developed yet. Since, the drug resistance is increasing day by day because the developed drug (nifurtimox and benznidazole) to control T. cruzi infection, failed to activate a prodrug and still no drug and vaccine have been established. To control the infection of chagas disease, here in this study we use immunoinformatics method to design multi-epitope subunit vaccine against T. cruzi infection. Moreover, on the basis of immunogenicity B and T cell epitopes were evaluated. The allergenicity, antigenicity was predicted to ensure the safety of vaccine constructs whereas, the physiochemical property showing the stable nature of final vaccine model. Further, molecular docking was performed to optimize the interaction between TLR-2 and TLR-4 (receptor) and vaccine model (ligand) complex. Molecular dynamics simulation was performed to evaluate the energy minimization; RMSD and RMSF plot which confirm the stability of TLR-2 and TLR-4 (receptor) present on immune cells and vaccine model (ligand) complex. This study needed the experimental validation for the safety and immunogenic behavior of designed vaccine protein and it may be helpful in future to control T. cruzi infection.


Proliferation of parathyroid cells negatively correlates with expression of parathyroid hormone-related protein in secondary parathyroid hyperplasia.
Parathyroid hormone-related protein (PTHrP) is now suspected to act as an autocrine or paracrine regulator of cell growth or differentiation, although it was originally reported as a hypercalcemic substance in malignancies. This study was performed to assess the relationship between PTHrP expression and cell proliferation in human parathyroid glands. The localization of PTH and PTHrP was studied in 42 samples of hyperplastic parathyroid from 14 long-term hemodialysis cases with immunohistochemistry and in situ hybridization. Results were compared with proliferative activity (proliferating cell nuclear antigen index: counts of proliferating cell nuclear antigen-positive cells/100 cells). The localization of the PTH/PTHrP receptor was also examined. Ten normal glands were studied as controls. In hyperplasia, cells positive for PTH, PTHrP, or both were observed immunohistochemically. The areas expressing PTHrP mRNA completely coincided with those positive for PTHrP immunohistochemically. Oxyphilic or transitional oxyphilic cells were consistently positive for PTHrP. PTH/PTHrP receptors were located in the cytoplasmic membrane in most parathyroid cells. Proliferating cell nuclear antigen-positive cells were rare in normal glands with an index of 0. 22 +/- 0.09 (mean +/- sem). They were significantly increased in hyperplastic cases but less for PTHrP-positive than for -negative cells (1.25 +/- 0.16 as compared with 7.80 +/- 0.52; P < 0.0001). The observed low level of proliferation of PTHrP-positive cells suggests a functional role for PTHrP as a possible growth suppressor in the human parathyroid.


Schizophrenic-like sensorimotor gating abnormalities in rats following dopamine infusion into the nucleus accumbens.
Previous studies have demonstrated that several dopamine agonists disrupt sensorimotor gating as measured by prepulse inhibition (PPI) of the acoustic startle response (ASR) in rats. Schizophrenic patients also exhibit deficits in PPI when the prepulse precedes the startle stimulus by less than 500 ms. In experiment 1, dopamine (0-40 micrograms) infused directly into the nucleus accumbens in rats caused a dose-dependent decrease in PPI at prepulse intervals shorter than 500 ms. In experiment 2, this effect of accumbens dopamine infusion on sensorimotor gating was found to vary with changes in prepulse intensity. These findings strongly suggest that increased mesolimbic dopamine activity is one substrate of the sensorimotor gating deficits in rats that are caused by treatment with dopamine agonists; similar substrates might mediate deficits in PPI exhibited by schizophrenic patients.


A waste-based circular economy approach for phycoremediation of X-ray developer solution.
A waste-based circular economy approach is proposed for the phycoremediation of an X-ray developer (XD) solution. The present study emphasizes the utilization of food waste (FW) and agri-compost media (ACM) as growth media for D. armatus for the subsequent bioremediation potential of XD solution-coupled lipid production. A 3:1 dilution (FW/ACM: XD.) was found to be suitable for the phycoremediation study of XD solution towards the % removal of biological oxygen demand (BOD), chemical oxygen demand (COD) and silver. The phycoremediation studies of diluted XD solution in FW demonstrated a 74.50% BOD removal, 81.69% COD removal, and 54.70% removal of silver. The growth of D. armatus in diluted XD solution in food waste was 1.37% lipid content. The phycoremediation of diluted XD solution with ACM resulted in 83.05% BOD removal, 88.88% COD removal and 56.30% silver removal with the concomitant lipid production of 1.42%. The optimal bioremediation coupled lipid production of D. armatus was observed on the 19th day of D. armatus cultivation in the developer effluent, along with food waste and agri-compost media, for 31 days. The study suggests a sustainable utilization of waste (FW and ACM) as a nutritive medium to scrutinize the phycoremediation of XD solution with a concomitant lipid production that can open up new avenues in phycoremediation coupled energy commodities production.


Significance of temperature fluctuation and oxygen concentration for germination of the rice field weeds Fimbristylis littoralis and Scirpus juncoides.
A diurnally fluctuating temperature was found to be almost an absolute requirement for the germination of Fimbristylis littoralis and Scirpus juncoides. It is demonstrated that in f. littoralis sensitivity to the amplitude of temperature fluctuation can functuation as a depth sensing mechanism under water. This species did not germinate at all in the absence of oxygen. S. juncoides germinated best in anaerobic conditions and at low oxygen concentrations, but normal atmospheric concentrations inhibited germination. It is shown that this requirement for little or no oxygen together with the requirement for a fluctuating temperature cause the germination of S. juncoides to be restricted to the upper layers of waterlogged soil.


Effects of corrective and breathing exercises on respiratory function of older adults with a history of COVID-19 infection: a randomized controlled trial.
Patients with a history of COVID-19 infection may suffer from different physical problems. This study aimed to investigate the effect of corrective and breathing exercises on improving respiratory function among patients with a history of COVID-19 infection. In this clinical trial study, thirty elderlies with a history of COVID-19 disease were divided into two groups (mean age 63.60 ± 3.56 experimental, 59.87 ± 2.99 control groups) based on the study inclusion criteria. Exercise interventions included two sections- breathing exercises and corrective exercises in the cervical and thoracic spine. The spirometry test, craniovertebral angle, and thoracic kyphosis test were used. To evaluate differences between variables, paired-samples t-test and ANCOVA were used (p-value < 0.01). Also, Eta-squared was measured to assess the effect size. Results showed a significant difference between the two groups in craniovertebral angle (P = 0.001), thoracic kyphosis (P = 0.007), and respiratory capacity including Forced expiratory volume in one second (FEV1) (P = 0.002), FEV1/FVC (P = 0.003), Peripheral oxygen saturation (SPO2) (P = 0.001), while no significant differences were observed between two groups in terms of chest anthropometric indices (P > 0.01). The Eta-squared value of 0.51 for the Craniovertebral angle and the SPO2 indicates a large effect size. The results showed the combination of corrective and breathing exercises could improve pulmonary function and correct cervical and thoracic posture in patients with a history of COVID-19 infection. Therefore, corrective and breathing exercises can be helpful as a complementary treatment along with pharmaceutical therapy to reduce chronic pulmonary complications in patients infected with COVID-19. This research was registered in the Iranian Registry of Clinical Trials (IRCT registration number: IRCT20160815029373N7, First trial registration: 23/08/2021, Registration date: 01/09/2021).


Association of Referral Source and Substance Use with Hepatitis C Virus Outcomes at a Southern Academic Medical Center.
Therapeutic advances make the cure of chronic hepatitis C virus (HCV) infection achievable for individuals aware of their diagnosis who can access care. Identifying barriers to accessing care is critical to achieve population-level HCV elimination and improve the cascade of care from diagnosis to cure. To identify barriers to HCV care, we performed a retrospective observational analysis of outcomes for patients with chronic HCV referred to an infectious diseases clinic at an academic medical center in Charleston, South Carolina between January 1, 2015 and January 1, 2020. We categorized outcomes in the cascade of care between "never presenting for evaluation" and "completed treatment with documented cure." Patient demographic factors, referral source, ZIP code of residence, insurance status, clinical characteristics, antiviral regimen, psychiatric and substance use history, and route of infection were assessed for associations with care outcomes. Of 407 referrals, 32% of patients never presented for an initial evaluation, an outcome that was associated with active substance use, mental health disease, and referral from an emergency department or obstetrics-gynecology provider. Of the patients who presented for an initial evaluation, 78% of patients initiated treatment. Active substance use was the only variable associated with lack of therapy initiation after presenting for an initial evaluation (odds ratio 2.5, 95% confidence interval 1.07-5.84). Once treatment had been initiated, no clinical or demographic variables were associated with odds of achieving documented or presumed HCV cure. Active substance use, mental health disease, and referral from an emergency department or obstetrics-gynecology provider were associated with a lower odds of presenting for evaluation and initiation of HCV treatment. Innovative models to improve access to care and increase outreach to vulnerable populations will be essential to eliminate HCV.


[Stress perfusion tomography of the myocardium using the 201 thallium isotope in cardiac surgery--evaluation of initial results].
Initial results of evaluation of scintigraphic examinations by means of the isotope 201thallium indicate the importance of this method in cardiosurgery, in particular in the postoperative evaluation of the effect of bypass operations. In patients with an objective improvement on the postoperative scintigrams also subjective improvement of the condition was recorded.


Prognostic value of Ki-67 in solid pseudopapillary tumor of the pancreas: Huashan experience and systematic review of the literature.
Solid pseudopapillary tumor of the pancreas (SPTP) is considered to have a low Ki-67 proliferation index, which may explain the generally good clinical outcome. The aim of our study was to evaluate whether Ki-67 has prognostic value in SPTP. A case series study of patients with SPTP treated in our institution from June 2002 to April 2014 was conducted. Prognostic factors for clinical outcomes were analyzed by the use of clinical decision and survival analysis. In addition, we performed a systematic review and pooled analysis to evaluate our results. The institutional data included 71 patients (13 male and 58 female) ranging in age from 12 to 64 years (median, 31 years). Three patients developed local recurrence and/or liver metastasis after initial surgery. The 5-year recurrence-free survival rate was 93.6%. One patient died of disease, with the 5-year disease-specific survival rate of 98.5%. Ki-67 index ≥ 4% was found significantly associated with the survival of SPTP. Twenty-six studies comprising 163 patients were included in the pooled analysis based on our inclusion criteria. A total of 15 cases showed a Ki-67 index ≥ 4%. Kaplan-Meier survival analysis confirmed that Ki-67 index ≥ 4% was significantly associated with poorer recurrence-free survival and disease-specific survival (both P < .001). This study highlighted a potential role of Ki-67 in predicting adverse outcome of patients with SPTP and should be considered as part of routine histological reporting of SPTP.


Rare association of traumatic diaphragmatic hernia with spinal cord injury: A case report.
The traumatic diaphragmatic hernia could be missed in the background of spinal fractures due to neurological weakness. We report the first case of the management of thoracolumbar fracture-dislocation associated with diaphragmatic injury. 53-year-old male transferred from local hospital following fallen from a motorbike on the 4th day after the injury. He was paraplegic from L1 below with sacral root involvement. Further imaging showed fracture-dislocation of the vertebral body at the T12-L1 level and anterior displacement of T11 on T12. The left-sided diaphragmatic hernia was detected by chest x-ray with bowel shadows in the left hemithorax. Emergency laparotomy and diaphragmatic repair followed by a posterior spinal exploration and pedicle screw fixation were done. Early mobilization was done after spinal fixation and the patient is successfully continuing rehabilitation. Thoracolumbar fracture-dislocation associated with the traumatic diaphragmatic hernia is rare. Clinical diagnosis of associated visceral injuries could be delayed due to the neurological deficit of the patient. An initial concern was to repair the life-threatening diaphragmatic hernia. Even current studies showed improved neurological function from early spinal surgery, spinal fixation had to delay as surgery needs a prone position. Early identification and management of traumatic diaphragmatic hernia are life-saving and allows early surgical intervention for the spine. Early reduction and fixation are associated with improved neurological function and will allow early mobilization and reduce hospital and ICU stay.


Cytomorphological features of metastatic squamous cell carcinoma in serous effusions.
To study the cytomorphological features of squamous cell carcinoma (SCC) in serous effusions. Conventional smears from 23 SCC were reviewed for the following features: cellularity, single cells, cell clusters, long cords, squamous pearls, cell-in-cell, 'windows', polygonal cells, anucleated cells, tadpole cells, fibre cells, third-type cells, refractile cytoplasmic ring, two-tone cytoplasm, cytoplasmic density, cytoplasmic vacuoles, signet ring cells, nuclear/cytoplasmic ratio, nuclear hyperchromasia, irregular nuclear membrane, nuclear centricity, double or multiple nuclei, nucleolus, anaplastic cells and mitosis. Subsequently, we also reviewed 15 reactive mesothelium, 18 mesotheliomas and 24 adenocarcinomas for comparison. Most SCC smears comprised mixed populations of single cells and cell clusters. Keratinized squamous cells and squamous pearls were diagnostic for well-differentiated SCC. Squamous eddies, appreciated on the cell block sections appearing as two-dimensional cell clusters with a swirling pattern, were characteristic for SCC. Poorly differentiated/third-type cells with atypical cytoplasmic keratinization, manifest as two-tone cytoplasm with a well-defined border and occasionally a refractile central ring, were an important clue for the squamous origin of the cells. Features including cell-in-cell, cytoplasmic vacuolation, double or multinucleated cells, anaplastic cells and mitotic figures were present in various degrees, and were not of diagnostic value. Certain cytological features are diagnostic for SCC, whereas other features of poorly differentiated SCC often overlap with those of reactive mesothelial cells, mesothelioma, metastatic adenocarcinoma or urothelial carcinoma in serous effusions. The combination of clinical history, appropriate immunohistochemical panel and cytomorphological features are important to ensure a correct diagnosis.


Benzene, 1,2,4-Trimethoxy-5-(2-Methyl-1-Propen-1-yl) Attenuates D-galactose/AlCl3-induced Cognitive Impairment by Inhibiting Inflammation, Apoptosis, and improving Expression of Memory-Related Proteins.
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by decreased learning ability and memory deficits. Our previous findings suggested that benzene, 1,2,4-trimethoxy-5-(2-methyl-1-propen-1-yl) (BTY) can ameliorate the dysfunction of GABAergic inhibitory neurons associated with neurological diseases. On this basis, we investigated the neuroprotective effect of BTY on AD and explored the underlying mechanism. This study included in vitro and in vivo experiments. BTY could maintain cell morphology, improve cell survival rate, reduce cell damage, and inhibit cell apoptosis in vitro experiments. Further, BTY has good pharmacological activity in vivo experiments, of which behavioral experiments showed that BTY could improve AD-like mice's learning and memory abilities. Besides, histopathological experiments indicated that BTY could maintain the morphology and function of neurons, reduce amyloid β-protein 42 (Aβ42) and phosphorylated tau (p-tau) accumulation, and decrease the levels of inflammatory cytokines. Finally, western blot experiments showed that BTY could inhibit the expression of apoptosis-related proteins and promote the expression of memory-related proteins. In conclusion, this study indicated that BTY may be a promising drug candidate for AD.


Phase diagrams and crossover in spatially anisotropic d = 3 Ising, XY magnetic, and percolation systems: exact renormalization-group solutions of hierarchical models.
Hierarchical lattices that constitute spatially anisotropic systems are introduced. These lattices provide exact solutions for hierarchical models and, simultaneously, approximate solutions for uniaxially or fully anisotropic d = 3 physical models. The global phase diagrams, with d = 2 and d = 1 to d = 3 crossovers, are obtained for Ising and XY magnetic models and percolation systems, including crossovers from algebraic order to true long-range order.


Challenges and future scope of exosomes in the treatment of cardiovascular diseases.
Exosomes are nanosized vesicles that carry biologically diverse molecules for intercellular communication. Researchers have been trying to engineer exosomes for therapeutic purposes by using different approaches to deliver biologically active molecules to the various target cells efficiently. Recent technological advances may allow the biodistribution and pharmacokinetics of exosomes to be modified to meet scientific needs with respect to specific diseases. However, it is essential to determine an exosome's optimal dosage and potential side effects before its clinical use. Significant breakthroughs have been made in recent decades concerning exosome labelling and imaging techniques. These tools provide in situ monitoring of exosome biodistribution and pharmacokinetics and pinpoint targetability. However, because exosomes are nanometres in size and vary significantly in contents, a deeper understanding is required to ensure accurate monitoring before they can be applied in clinical settings. Different research groups have established different approaches to elucidate the roles of exosomes and visualize their spatial properties. This review covers current and emerging strategies for in vivo and in vitro exosome imaging and tracking for potential studies.


Effects of the COVID-19 pandemic on breast cancer screening in Taiwan.
The breast cancer screening program has continued in Taiwan during the COVID-19 pandemic. Our nationwide data showed that the total number of screenings decreased by 22.2%, which was more pronounced for in-hospital examinations (-37.2%), while outreach showed a 12.9% decrease. This decline in screening participation happened at all levels of hospitals, more significantly at the highest level. Our report revealed that outreach services could maintain relatively stable breast cancer screening under this kind of public health crisis. Building a flexible, outreach system into the community might need to be considered when policymakers are preparing for future possible pandemics.


Automated sequential injection fluorimetric set-up for multiple release testing of topical formulation.
A fully automated sequential injection analysis (SIA) device for simultaneous release testing of multiple ointment samples was devised and applied to the release testing of an ointment containing salicylic acid as an active substance. The SIA system consisted of a bi-directional 5 ml syringe pump, two 8-position selection valves, auxiliary peristaltic pump, fluorescence detector and three Franz cells maintained at 32 degrees C (water bath). The ointment sample was placed on top of a synthetic Millipore GTTP poly(carbonate) membrane (thickness 10 microm, pore size 0.2 microm) of the Franz cell containing 15 ml of aqueous phosphate buffer of pH 7.4 as the acceptor liquid. The samples of the acceptor liquid (50 microl) were aspirated in 15 min intervals for the period of 6 h from each of the 3 cells and dispensed to a fluorescence detector to determine the concentration of salicylic acid (excitation at 297 nm and emission at 405 nm). The volume of the acceptor medium taken for analysis was automatically replenished after each measurement. The calibration curve was rectilinear for 1-100 microg ml(-1) of salicylic acid. The device allowed simultaneous monitoring of the release tests for up to six cells including automated computer-aided evaluation of the release profile parameters.


Understanding the critical disposition pathways of statins to assess drug-drug interaction risk during drug development: it's not just about OATP1B1.
The use of statins is widespread across disease areas because many patients have comorbidities. Given that these drugs have become common as comedications, it is essential to have an understanding of the potential risks of drug-drug interactions (DDIs) between statins and candidate drugs in development. Although the hepatic uptake transporter organic anion-transporting polypeptide 1B1 (OATP1B1) is known to play a substantial role in statin-related DDI risk, other transporters and metabolizing enzymes can also be involved. Consequently, a holistic approach to risk assessment is required, tailored to each statin. Using evidence from pharmacogenetics, DDIs, and literature on absorption, distribution, metabolism, and elimination (ADME) in humans, this review identifies pathways that contribute the most to, and are therefore the most critical to, the disposition of each statin. It also provides an understanding of the expected theoretical maximum increase in systemic exposure if the disposition of a statin is inhibited. Finally, on a statin-by-statin basis, we propose in vitro inhibition studies that should be routinely conducted during drug development so as to better assess DDI risk.


Effects of energy restriction on age-associated changes of DNA methylation in mouse liver.
DNA methylation is known to change with age in several mammalian species. Here we have examined the effect of dietary energy restriction on this age-associated change in liver DNA of C3H/SHN mice. The total 5-methyldeoxycytidine level in the genome decreased slightly soon after energy restriction started. The effect, however, diminished with time and no appreciable difference was detected at middle and old ages. The degree of methylation at the c-myc gene, on the other hand, was not affected by energy restriction at early periods, but the age-dependent alterations at later ages were repressed. This is a new finding to show that DNA methylation is one of the molecular indices of aging affected by energy restriction. It suggests an importance of DNA methylation in the aging process.


Interaction of Graphene Oxide Nanoparticles with Human Mononuclear Cells in the Cell-IQ System.
The interaction of graphene oxide nanoparticles with human peripheral blood mononuclear cells was studied using the Cell-IQ continuous monitoring system for living cells. We used graphene oxide nanoparticles of various sizes coated with linear or branched polyethylene glycol (PEG) in concentrations of 5 and 25 μg/ml. After 24-h incubation with graphene oxide nanoparticles, the increase in the number of peripheral blood mononuclear cells at visualization points decreased; nanoparticles coated with branched PEG more markedly suppressed cell growth in culture. In the presence of graphene oxide nanoparticles, peripheral blood mononuclear cells retained high viability in culture after daily monitoring in the Cell-IQ system. The studied nanoparticles were engulfed by monocytes and the type of PEGylation had no effect on this process. Thus, graphene oxide nanoparticles reduced the increase in peripheral blood mononuclear cell mass during dynamic observation in the Cell-IQ system without reducing their viability.


Two structural types of mercury reductases and possible ways of their evolution.
Structural differences have been revealed among mercury reductases of immunologically unrelated types from Gram-positive bacteria: enzymes of one immunological type have a molecular mass of 62-69 kDa and seem to contain an N-terminal extension of 5-15 kDa, which is easily cleaved by trypsin and chymotrypsin; enzymes of the other immunological type have a molecular mass of 52-57 kDa and are resistant to proteolysis. The existence of at least two different lines in the evolution of mercury reductases is surmised.


Recent Advances in Mycobacterial Research.
Worldwide, tuberculosis (TB) remains the most frequent and important infectious disease that is responsible for causing significant morbidity and death [...].


Sida tuberculata: In vitro cytotoxicity and in vivo anti-inflammatory effect.
Sida tuberculata R. E. Fries (Malvaceae) is a pioneer species considered a weed in farm fields in Southern Brazil. Widely distributed in South Brazil, S. tuberculata is popularly used to treat inflammatory conditions. The current study aimed to assess the in vitro cytotoxic and in vivo anti-inflammatory properties of S. tuberculata. Initially, extracts obtained from leaves (STLE) and roots (STRE) were submitted to cytotoxicity tests using human leukocytes (non-malignant cell line) and HepG2 and MCF-7 (tumor cell lines). In sequence, anti-inflammatory properties were investigated against carrageenan-induced peritonitis model. In vitro analyses displayed a significant decrease in human leukocytes viability without genotoxic damage. IC50 results from tumor cells presented significant decrease in cell viability, slightly more pronounced for STRE. In addition, STLE significantly inhibited the inflammatory and oxidative parameters (TBARS, NPSH, SOD, MPO activity, cell influx, and cytokines release). Our findings indicate S. tuberculata extracts have cytotoxic potential more pronounced on tumor cell lines, as well as leaves extract shows a significant reduction in acute inflammation process, as already reported for Sida genus and specifically for this species.


Mitochondria single nucleotide variation across six blood cell types.
It has been shown that heteroplasmic mitochondrial DNA variants can be tissue specific. However, whether mitochondrial DNA variants are specific by blood cell types has not been investigated. Motivated by this question and using mitochondria sequences extracted from RNAseq data from six distinct blood cell types (neutrophil, monocyte, myeloid dendritic, natural killer, T and B), we thoroughly compared SNPs and heteroplasmies among these cell types. Each cell type from each subject was sequenced at four time points used as biological replicates. We found that mitochondria content is low in neutrophil compared to the other five blood cell types. Subsequent analysis on the other five blood cell types showed that at the SNP level, there was no discrepancy. At the heteroplasmy level, we observed good concordances among all blood cell types. However, the allele frequencies of the heteroplasmy differed between blood cell types for certain heteroplasmic sites. Furthermore, we identified five tri-allelic sites (1610, 2617, 8303, 12146, 13710) that are likely caused by RNA editing. Three out of these five sites are located at the ninth position of tRNA genes, and are likely resulting from post-transcriptional methylation.


Intermediate bone grafting of alveolar clefts.
During the five year period 1980 to 1985 bone grafting was performed in 37 cleft patients before the eruption of the canine tooth (group IBG) and in 30 patients after the eruption of the canine tooth (group SGB). The initial healing was more favourable in the IBG group. In 72.5% of the clefts oro-nasal fistulae were present preoperatively. In all cases the fistulae were successfully closed. In the IBG group with orthodontic closure of the gap in the dental arch the interdental bone height in the grafted area was more than 75% of normal bone height in all clefts. In group SBG this situation was found in only 66% of the bone-grafted areas. There seems to be a clear relation between the age or the developmental stage of the canine tooth on the one hand and the possibility of orthodontic closure of the gap in the dental arch and good interdental bone height on the other hand. This also leads to the suggestion that if bone grafting to the alveolar cleft is required the operation should be performed before the eruption of the canine tooth on the cleft side.


[Salivary gland tumor of the hard palate].
Pleomorphic adenomas of the small salivary glands are very rare and usually arise from the hard palate. We present a female patient who was referred to our Department because of a bleeding enoral tumor, which persisted for 35 years. Histopathological examination after complete tumor excision showed a pleomorphic adenoma. Pleomorphic adenomas are an important differential diagnosis for tumors of the hard palatine. The therapy of choice is surgical excision.


Targeting impaired nutrient sensing via the sirtuin pathway with novel compounds to prevent or treat dementia: A systematic review.
Dementia is prevalent in aged populations and is associated with disability and distress for those affected. Therapeutic benefits of drugs targeting dementia are small. Impaired nutrient sensing pathways have been implicated in the pathogenesis of dementia and may offer a novel treatment target. This systematic review collated evidence for novel therapeutic compounds that modify nutrient sensing pathways, particularly the sirtuin pathway, in preventing cognitive decline or improving cognition in normal ageing, mild cognitive impairment (MCI), and dementia. PubMed, Embase and Web of Science databases were searched using key search terms. Articles were screened using Covidence systematic review software. The risk of bias was assessed using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE)'s risk of bias tool for animal studies and Cochrane Risk of Bias tool v 2.0 for human studies. Out of 3841 articles, 68 were included describing 38 different novel therapeutic compounds that modulate the nutrient sensing pathway via the sirtuin pathway. In animal models (58 studies), all investigated novel therapeutic compounds showed cognitive benefits. Ten studies were human intervention trials targeting normal ageing (1 study) and dementia populations (9 studies). Direct sirtuin (silent mating type information regulation 2 homolog) 1 (SIRT1) activators Resveratrol and Nicotinamide derivatives improved cognitive outcomes among human subjects with normal cognition and MCI. Animal studies support that modulation of the sirtuin pathway has the potential to improve cognitive outcomes. Overall, there is a clear lack of translation from animal models to human populations.


Adenosarcoma of uterus and ovary: a clinicopathologic study of two cases.
We report the clinical and pathologic features of two cases of adenosarcoma. Our first case occurred in the ovary of a 51-year-old woman with extensive pelvic involvement. She was treated vigorously with radiation and chemotherapy and at the present time almost 9 years later the patient is free of disease. This represents a case with one of the longest survival reported in the literature. Our second case occurred in a 37-year-old woman and was limited to the endometrium.


Immuno-localization of Fas and FasL in rat hepatic endothelial cells: influence of different fixation protocols.
Immunocytochemistry has been widely used to localize molecules involved in apoptosis. In this short report, we describe with the aid of confocal laser scanning microscopy the immunolocalization of Fas and FasL on liver sinusoidal endothelial cells, and show how the localization of these two molecules differ when the cells are fixed with different fixation protocols. Methanol fixation shows diffuse staining of Fas and FasL in the cytoplasm, as well as in the nucleus. In contrast, paraformaldehyde fixation reveals the presence of Fas and FasL polarized at one side of the cell and only in the cytoplasm. After fixation with a combination of paraformaldehyde and glutaraldehyde the polarization is still present although the fluorescence is concentrated and located as bright dots in the cytoplasm. In conclusion, paraformaldehyde preserves the (nuclear) membrane-associated structures better then methanol and results in a more accurate localization of Fas and FasL. Understanding the different outcome of these common used fixation protocols will assist investigators to select the most suitable method for visualizing membrane-bound Fas and FasL.


Analysis of telomere length and telomerase activity in tree species of various life-spans, and with age in the bristlecone pine Pinus longaeva.
Normal somatic cells have a finite replicative capacity. With each cell division, telomeres (the physical ends of linear chromosomes) progressively shorten until they reach a critical length, at which point the cells enter replicative senescence. Some cells maintain telomere length by the action of the telomerase enzyme. The bristlecone pine, Pinus longaeva, is the oldest known living eukaryotic organism, with the oldest on record turning 4770 years old in 2005. To determine what changes occur, if any, in telomere length and telomerase activity with age, and what roles, if any, telomere length and telomerase activity may play in contributing to the increased life-span and longevity of P. longaeva with age, as well as in other tree species of various life-spans, we undertook a detailed investigation of telomere length and telomerase activity in such trees. The results from this study support the hypothesis that both increased telomere length and telomerase activity may directly/indirectly contribute to the increased life-span and longevity evident in long-lived pine trees (2000-5000 year life-spans) compared to medium-lived (400-500 year life-span) and short-lived (100-200 year life-span) pine trees, as well as in P. longaeva with age.


Physiological strains induce differentiation in human osteoblasts cultured on orthopaedic biomaterial.
We have developed an in vitro mechanical stretching model of osteoblastic cells cultured on metallic biomaterials in order to study the effects of mechanical strain on osteointegration of orthopaedic implants. Titanium alloy discs coated with alumina or hydroxyapatite were used as substrates. Three Dynacell devices were especially designed to apply cyclic strains on rigid biomaterials. The regimen (600 mu epsilon strains, 0.25Hz) was defined on the basis of physiological data and estimated deformation on hip stem prostheses. The performances of these apparatus were reproducible and provided controlled deformations. Human osteosarcoma cell line MG-63, human osteoblasts obtained from primary cultures and ROS 17/2.8 rat osteosarcoma cells were used as cell models. Cell behaviour was assessed in terms of growth and alkaline phosphatase (ALP) activity by in situ assays for two regimens: 15-min deformations repeated three times a day to mimic rehabilitation exercises and 24-h continuous deformations. We demonstrated that continuous deformation did not affect the growth and ALP activity of MG-63 cells, in contrast with sequential deformations which had no effect on cell number, but which stimulated ALP activity after 5 days of stretching. This sequential regimen can also modify the behaviour of human bone-derived cells resulting in increased proliferation after 5 days and stimulation of ALP activity after 15 days. ROS 17/2.8 rat osteosarcoma cells submitted to sequential deformations responded faster than other cell lines by increasing their ALP activity only after 1 day of stretching. Like MG-63 cells, proliferation of the ROS 17/2.8 rat osteosarcoma cell line was not affected by sequential deformations. This study suggests that short, repeated deformations defined to mimic rehabilitation exercises recommended after prostheses implantation are more likely to exert beneficial effects on implanted bone than continuous strains.


[Surgical shock. Acute hypocatecholaminemia and therapeutic indications of an adrenocortical vasopressor sympathicolytic drug mixture. Clinical studies and experimental research].
In cases with postoperative shock and collapse a constant fall in the concentration of serum cathecholamines was noted. Thus adrenalin was reduced by 77%, noradrenalin by 86.5%, in direct proportion with the fall in the blood pressure, of the pulse amplitude and with the slowing-down (or the arrest) of the microcirculation. The reduction of serum cathecholamines also coincided with a decrease in the amount of buffer bases and of the diuresis. The adrenocortical vasopresor sympathicolithic mixture is indicated in the prolonged arterial hypotension following failure of therapy aimed at filling of the vascular bed associated with the administration of sympathicolytic drugs.


Mycobacterial infection induces the secretion of high-mobility group box 1 protein.
High-mobility group box protein 1 (HMGB1) is a non-histone nuclear protein that acts as a pro-inflammatory cytokine and is released by monocytes and macrophages. Necrotic cells also release HMGB1 at the site of tissue damage which induces a variety of cellular responses, including the expression of pro-inflammatory mediators. This study investigated the secretion of HMGB1 in mycobacterial infection by macrophages in vitro and in the lungs of infected guinea pigs. We observed that infection by mycobacterium effectively induced HMGB1 release in both macrophage and monocytic cell cultures. Culture filtrate proteins from Mycobacterium tuberculosis induced maximum release of HMGB1 compared with different subcellular fractions of mycobacterium. We demonstrated that HMGB1 is released in lungs during infection of M. tuberculosis in guinea pigs and increased HMGB1 secretion in lungs of guinea pigs was delayed by prior vaccination with Mycobacterium bovis BCG. The secretion of cytokines like tumour necrosis factor alpha (TNF-alpha) and Interleukin-1beta was significantly increased when M. bovis BCG-infected cultures of J774A.1 cells were incubated with HMGB1. Among different mycobacterial toll-like receptor ligands, heat-shock protein 65 (HSP65) was found to be more potent in inducing HMGB1 secretion in RAW 264.7 cells. Pharmacological suppression of p38 or extracellular signal-regulated kinase 1/2 mitogen-activated protein kinases with specific inhibitors failed to inhibit HSP65-induced HMGB1 release, but inhibition of c-Jun NH(2)-terminal kinase activation attenuated HMGB1 release. Inhibition of the inducible NO synthase and neutralizing antibodies against TNF-alpha also reduced HMGB1 release stimulated by HSP65. We conclude that HMGB1 is secreted by macrophages during tuberculosis and it may act as a signal of tissue or cellular injury and enhances immune response.


Removal of eye movement and ECG artifacts from the non-cephalic reference EEG.
A method is described that automatically eliminates eye movement artifacts from EEG records and creates an extracranial reference electrode in one single process. The usefulness of this method is illustrated for both standard EEG recording as well as for CNV and P300 potentials. The artifact signals are measured with a special set of electrodes and are combined in order to subtract the artifacts from contaminated EEG records. The subtraction ratios are determined as those that minimize the variance in the result corrected EEG signal.


FAS promoter polymorphisms correlate with activity grade in hepatitis C patients.
Hepatocytes are susceptible to FAS-mediated apoptosis. The impact of polymorphisms in the FAS gene on histopathological features of HCV infection was therefore investigated. Three single-nucleotide polymorphisms in the FAS promoter were assessed in 190 patients with chronic hepatitis C. Associations between FAS haplotypes and fibrosis stage and activity grade were tested by univariate and multivariate analyses. While there was no correlation between FAS promoter genotype and fibrosis stage, patients carrying the GCA haplotype (P=0.03, Fisher's exact test) and those homozygous for the GTG haplotype (P = 0.06) tended to have lower activity scores. Logistic regression showed that these associations were independent of patient age, sex and alcohol consumption. In a logistic regression model incorporating only male gender (odds ratio 2.1, 95% confidence interval 1.1-4.1 P = 0.04), the presence of the GCA haplotype (OR 0.31 95% CI 0.13-0.78 P = 0.01), and GTG homozygosity (OR 0.26 95% CI 0.08-0.83 P = 0.02), all three factors were independently correlated with activity grade. Furthermore, the GTG haplotype appeared to have lower promoter activity than the wild type GTA haplotype in a hepatocellular carcinoma cell line. Genetic polymorphism in the FAS gene may account for some of the histopathological variability in chronic hepatitis C.


Cloning of inulin fructotransferase (DFA III-producing) gene from Arthrobacter sp. L68-1.
A gene of inulin fructotransferase (DFA III-producing) [EC 18.104.22.168] from Arthrobacter sp. L68-1 was cloned and the nucleotide was sequenced. The gene encoded a signal peptide (32 amino acid residues) for a secretion, and the mature enzyme protein was estimated to be consisted with 410 amino acid residues. The molecular mass of the native enzyme was calculated as 43.7kDa by the sequence data. The deduced amino acid sequence of the enzyme had 79.0% homology with that of the Arthrobacter globiformis C11-1, and had 77.4% homology with that of the Arthrobacter sp. H65-7. It also had 43.7% homology with that of inulin fructotransferase (DFA I-producing) [EC 18.104.22.168] from A. globiformis S14-3. The cloned enzyme was immobilized using Chitopearl BCW 3510 as a carrier. The immobilized enzyme was able to use 10 times without a significant loss of the enzyme activity.


Casino Gambling in Adolescents: Gambling-Related Attitudes and Behaviors and Health and Functioning Relationships.
Recreational and problem gambling have been linked with adverse health and functioning outcomes among adolescents. Youth may gamble and engage in other risk-taking behaviors in casinos. There are limited data available regarding casino gambling in high-school students, and factors linked to adolescent gambling in casinos have yet to be systematically investigated. To address this gap, we analyzed cross-sectional data from 2010 Connecticut high-school students with chi-square tests and logistic regression models to examine casino gambling in relation to at-risk/problem gambling (ARPG) with respect to sociodemographic characteristics, gambling perceptions & attitudes, health/functioning measures and gambling behaviors. Approximately 11 % of adolescents acknowledged gambling in casinos. ARPG was more frequent and gambling perceptions were more permissive among adolescents endorsing casino gambling. Stronger relationships between ARPG and heavy alcohol and drug use and weaker relationships between ARPG and engagement in extracurricular activities, gambling with friends, gambling with strangers and gambling for financial reasons were observed among adolescents endorsing casino gambling. In conclusion, gambling in casinos was endorsed by a sizable minority of adolescents who gamble, and prevention efforts should consider targeting permissive attitudes towards gambling, adolescent drinking and participation in extracurricular activities when addressing underage casino gambling.


Interfacial "Single-Atom-in-Defects" Catalysts Accelerating Li+ Desolvation Kinetics for Long-Lifespan Lithium-Metal Batteries.
The lithium-metal anode is a promising candidate for realizing high-energy-density batteries owing to its high capacity and low potential. However, several rate-limiting kinetic obstacles, such as the desolvation of Li+ solvation structure to liberate Li+ , Li0 nucleation, and atom diffusion, cause heterogeneous spatial Li-ion distribution and fractal plating morphology with dendrite formation, leading to low Coulombic efficiency and depressive electrochemical stability. Herein, differing from pore sieving effect or electrolyte engineering, atomic iron anchors to cation vacancy-rich Co1- x S embedded in 3D porous carbon (SAFe/CVRCS@3DPC) is proposed and demonstrated as catalytic kinetic promoters. Numerous free Li ions are electrocatalytically dissociated from the Li+ solvation complex structure for uniform lateral diffusion by reducing desolvation and diffusion barriers via SAFe/CVRCS@3DPC, realizing smooth dendrite-free Li morphologies, as comprehensively understood by combined in situ/ex situ characterizations. Encouraged by SAFe/CVRCS@3DPC catalytic promotor, the modified Li-metal anodes achieve smooth plating with a long lifespan (1600 h) and high Coulombic efficiency without any dendrite formation. Paired with the LiFePO4 cathode, the full cell (10.7 mg cm-2 ) stabilizes a capacity retention of 90.3% after 300 cycles at 0.5 C, signifying the feasibility of using interfacial catalysts for modulating Li behaviors toward practical applications.


Relationship between DNA ploidy and survival in patients with primary breast cancer.
The DNA ploidy of breast cancer tissue from paraffin blocks was measured by flow cytometry in 117 patients whose disease had been detected and treated with surgery between 1974 and 1976. Patients with aneuploid tumours had positive axillary nodes and distant metastases more often than those with diploid tumours. Aneuploid tumours were more common in postmenopausal than premenopausal women. The S-phase fraction (SPF) was significantly higher in aneuploid than in diploid tumours and positive axillary lymph nodes were found in 26 per cent of the patients who had a tumour with a SPF below the median (4.8 per cent) and in 48 per cent of those with tumours with SPF values above the median. At the primary clinical investigation 2 per cent of the patients with diploid tumours and 6 per cent of those with aneuploid tumours had distant metastases. During the follow-up, the proportion of patients with distant metastases increased to 42 and 72 per cent, respectively. With a follow-up of 11.5 years, the DNA aneuploidy of the tumour showed a significant association with decreased survival. Thirty-three per cent of patients with diploid and 65 per cent of patients with aneuploid tumours had died from breast cancer during the follow-up (P less than 0.001). All patients with hypertetraploid or multiploid tumours died from breast cancer. High SPF values were associated more closely with distant metastases or death during the follow-up than low SPF values. Our results suggest that DNA ploidy measured by flow cytometry from paraffin embedded tissue blocks of human breast cancer can be used to predict the aggressiveness of the tumour and the survival of the patients.


Quantitative structure-activity relationship analysis of phenolic antioxidants.
In this report, the quantitative structure-activity relationship (QSAR) analyses of substituted phenols, vitamin E derivatives and flavonoids are presented. Two models have been derived using calculated parameters such as the heat of formation (Hf), the energy of the lowest unoccupied molecular orbital of radicals (E(lumo-r)) the energy of the highest occupied molecular orbital of the parent compounds (E(homo)) and the number of hydroxyl groups (OH). These models can be used to estimate the redox potentials or antioxidant activities of new substituted phenolic compounds or vitamin E derivatives. The Trolox equivalent antioxidant capacities (TEACs) of 42 different flavonoids are found to be mainly governed by the number and location of hydroxyl groups on the flavonoid ring system.


Sinus node dysfunction concomitant with Brugada syndrome.
A genetic correlation between Brugada syndrome (BS) and sinus node dysfunction (SND) has been proposed, although the clinical and electrophysiologic characteristics of this concomitant condition are unknown. The study comprised 5 patients with symptomatic BS (4 with spontaneous episodes of ventricular fibrillation (VF) and 1 with syncope) of whom 3 had a documented sinus pause > 3 s (a 42- and 62-year-old man, and a 49-year-old woman). Only 1 of them had a family history of sudden death; 2 of them had also had an episode of atrial fibrillation or flutter. Electrophysiologic study demonstrated prolonged sinus node recovery time in 2 patients (2.6 s and > 5 s), in whom a cardiac pacemaker had been implanted before the diagnosis of BS was made after episodes of VF. Finally, all 3 patients received an implantable cardioverter defibrillator, including 2 upgrades from pacemaker. SND is not a rare concomitant disorder in BS and there is a possible genetic connection.


Prosthetic breast reconstruction in previously irradiated breasts: A meta-analysis.
The present review evaluated the impacts of pre-reconstruction radiotherapy on outcome of prosthetic breast reconstruction and compared the safety of prosthetic reconstruction with that of other modalities, including autologous tissue reconstruction and the combination of flap and implant in the setting of pre-reconstruction radiation. Studies presenting outcomes of prosthetic breast reconstruction in the setting of pre-reconstruction radiation published in the past 10 years were identified and reviewed. Twenty studies were analyzed. Prosthetic reconstruction in previously irradiated breasts showed significantly increased risks for complications, including reconstruction failure (relative risk, 2.58; 95% confidence interval, 1.86-3.57) than those cases without radiation, regardless of the specific surgical technique used, including one-/two-stage reconstruction, use of an acellular dermal matrix or not, and the timing of the reconstruction (immediate/delayed). Autologous tissue reconstruction and a combination flap and implant showed a 92% and 72% decreased risk of reconstruction failure, respectively, in previously irradiated breasts compared with that of prosthetic reconstruction. The results suggest that prior irradiation significantly increases the risk of complications in patients undergoing prosthetic reconstruction, and using an autologous flap or combining it with an implant can be considered to reconstruct previously irradiated breasts.


Effect of different bariatric surgery type on the leukocyte formula.
Obesity is associated with higher leukocyte counts, whereas weight loss decreases these counts. It is unknown if different bariatric surgery (BS) types have different effects on leukocytes. The aim of the study was to determine predictors of leukocyte and their subset count variation in patients submitted to BS. Tertiary care university hospital, Porto, Portugal. This was a retrospective analysis of patients submitted to Roux-en-Y gastric bypass (RYGB), laparoscopic adjustable gastric banding (LAGB), or sleeve gastrectomy (SG). Leukocyte and subset counts were compared between baseline and 1-year postsurgery and between BS types. A multivariate linear regression model was built to study determinants of leukocyte and subset variation. We analyzed 764 patients: 238 submitted to LAGB; 452 to RYGB, and 74 to SG. Mean age was 42 years and 86.6% were women. All BS types were associated with a decrease in leukocyte and neutrophil counts but the variation in body mass index and homeostatic model assessment (HOMA-IR) were the only variables independently associated with a decrease 1-year postsurgery. Monocytes increased in patients submitted to LAGB and decreased in those who underwent RYGB and SG. The BS type was independently associated with monocyte variation. Patients who underwent RYGB and SG had a decrease in monocyte counts of 77/µL and 62/µL, respectively, compared with LAGB. Weight and insulin resistance are the main predictors of leukocyte and neutrophil variation after BS. The specific type of BS is a determinant of monocyte count variation independent of the amount of weight loss or the degree of insulin resistance improvement.


Relocalization of human chromatin remodeling cofactor TIP48 in mitosis.
TIP48 is a highly conserved eukaryotic AAA+ protein which is an essential cofactor for several complexes involved in chromatin acetylation and remodeling, transcriptional and developmental regulation and nucleolar organization and trafficking. We show that TIP48 abundance in HeLa cells did not change during the cell cycle, nor did its distribution in various biochemical fractions. However, we observed distinct changes in the subcellular localization of TIP48 during M phase using immunofluorescence microscopy. Our studies demonstrate that in interphase cells TIP48 was found mainly in the nucleus and exhibited a distinct localization in the nuclear periphery. As the cells entered mitosis, TIP48 was excluded from the condensing chromosomes but showed association with the mitotic apparatus. During anaphase, some TIP48 was detected in the centrosome colocalizing with tubulin but the strongest staining appeared in the mitotic equator associated with the midzone central spindle. Accumulation of TIP48 in the midzone and the midbody was observed in late telophase and cytokinesis. This redeployment of TIP48 during anaphase and cytokinesis was independent of microtubule assembly. The relocation of endogenous TIP48 to the midzone/midbody under physiological conditions suggests a novel and distinct function for TIP48 in mitosis and possible involvement in the exit of mitosis.


Familial Prader-Willi syndrome with apparently normal chromosomes.
We report on 4 sibs (2F, 2M) with Prader-Willi syndrome (PWS). Diagnosis was made clinically on the basis of history, behavior, and physical findings in 3 of the sibs. The other child had died at age 10 months with a history and clinical findings typical of first phase of PWS. Results of chromosome studies on the parents and surviving sibs were normal. The implications of this unusual familial occurrence for our understanding of PWS are discussed.


Midazolam and remifentanil by bolus injection for intensely stimulating procedures of brief duration: experience with awake laryngoscopy.
The pharmacokinetic characteristics of midazolam and remifentanil administered by bolus injection may make them advantageous for providing brief, intense analgesia without prolonged respiratory depression. This application is particularly useful for awake, direct laryngoscopy.


More than culture: structural racism, intersectionality theory, and immigrant health.
Explanations for immigrant health outcomes often invoke culture through the use of the concept of acculturation. The over reliance on cultural explanations for immigrant health outcomes has been the topic of growing debate, with the critics' main concern being that such explanations obscure the impact of structural factors on immigrant health disparities. In this paper, we highlight the shortcomings of cultural explanations as currently employed in the health literature, and argue for a shift from individual culture-based frameworks, to perspectives that address how multiple dimensions of inequality intersect to impact health outcomes. Based on our review of the literature, we suggest specific lines of inquiry regarding immigrants' experiences with day-to-day discrimination, as well as on the roles that place and immigration policies play in shaping immigrant health outcomes. The paper concludes with suggestions for integrating intersectionality theory in future research on immigrant health.


Pediatric brain tumors in Nigeria: clinical profile, management strategies, and outcome.
Although modern neuroimaging has facilitated early care of brain tumors in children worldwide, there are, however, few published reports on clinical profile, treatment, and outcome of brain tumors in children from our subregion. We aimed to retrospectively study the clinical profile and outcome of pediatric brain tumors in a tertiary referral center from a developing country. Forty pediatric patients with histologically verified brain tumors managed by the authors over a 13-year period (May 1994-April 2006) were studied. Patients' data from clinical, radiological, and pathology records were analyzed using the statistical package for social sciences version 16. The mean age was 9.75 years (range 1-15 years). Twenty-two males, 18 females. Common presenting symptoms were headaches (23 patients, 57.5%) and seizures (15 patients, 37.5%). Hyperreflexia (72.5%) and focal motor deficits (62.5%) were the most common neurologic signs. The mean interval from onset of symptoms to neurosurgical diagnosis was 13.4 months (95% CI). All patients had tumor resection, while 11 (27.5%) patients received adjuvant radiotherapy. Hydrocephalus occurred in 19 (47.5%) patients and was associated with early presentation (X2 = 10.65, p < 0.01). Low-grade astrocytoma (25%) and medulloblastoma (25%) were the most common tumors. Survival at 1 and 5 years were 56 and 47%, respectively. Focal motor signs and elevated intracranial pressure are the salient presenting features of brain tumors in children seen in Nigeria. Those of them with hydrocephalus are likely to present early. The outcome for pediatric brain tumors remains poor.


Performance and exploration of ChatGPT in medical examination, records and education in Chinese: Pave the way for medical AI.
Although chat generative pre-trained transformer (ChatGPT) has made several successful attempts in the medical field, most notably in answering medical questions in English, no studies have evaluated ChatGPT's performance in a Chinese context for a medical task. The aim of this study was to evaluate ChatGPT's ability to understand medical knowledge in Chinese, as well as its potential to serve as an electronic health infrastructure for medical development, by evaluating its performance in medical examinations, records, and education. The Chinese (CNMLE) and English (ENMLE) datasets of the China National Medical Licensing Examination and the Chinese dataset (NEEPM) of the China National Entrance Examination for Postgraduate Clinical Medicine Comprehensive Ability were used to evaluate the performance of ChatGPT (GPT-3.5 and GPT-4). We assessed answer accuracy, verbal fluency, and the classification of incorrect responses owing to hallucinations on multiple occasions. In addition, we tested ChatGPT's performance on discharge summaries and group learning in a Chinese context on a small scale. The accuracy of GPT-3.5 in CNMLE, ENMLE, and NEEPM was 56% (56/100), 76% (76/100), and 62% (62/100), respectively, compared to that of GPT-4, which was of 84% (84/100), 86% (86/100), and 82% (82/100). The verbal fluency of all the ChatGPT responses exceeded 95%. Among the GPT-3.5 incorrect responses, the proportions of open-domain hallucinations were 66 % (29/44), 54 % (14/24), and 63 % (24/38), whereas close-domain hallucinations accounted for 34 % (15/44), 46 % (14/24), and 37 % (14/38), respectively. By contrast, GPT-4 open-domain hallucinations accounted for 56% (9/16), 43% (6/14), and 83% (15/18), while close-domain hallucinations accounted for 44% (7/16), 57% (8/14), and 17% (3/18), respectively. In the discharge summary, ChatGPT demonstrated logical coherence, however GPT-3.5 could not fulfill the quality requirements, while GPT-4 met the qualification of 60% (6/10). In group learning, the verbal fluency and interaction satisfaction with ChatGPT were 100% (10/10). ChatGPT based on GPT-4 is at par with Chinese medical practitioners who passed the CNMLE and at the standard required for admission to clinical medical graduate programs in China. The GPT-4 shows promising potential for discharge summarization and group learning. Additionally, it shows high verbal fluency, resulting in a positive human-computer interaction experience. GPT-4 significantly improves multiple capabilities and reduces hallucinations compared to the previous GPT-3.5 model, with a particular leap forward in the Chinese comprehension capability of medical tasks. Artificial intelligence (AI) systems face the challenges of hallucinations, legal risks, and ethical issues. However, we discovered ChatGPT's potential to promote medical development as an electronic health infrastructure, paving the way for Medical AI to become necessary.


Preventing cancer: a community-based program for youths in public housing.
This article describes a feasibility study of a program that mentors boys aged 14-18 living in inner city public housing, engages them in a basketball league, and provides educational sessions on life skills and ways to resolve conflicts without violence. Such programs have the potential to engage adolescent males living in public housing in activities that reduce cancer-related behaviors and increase protective behaviors. We conducted a feasibility evaluation of the program, which included a survey of participants, interviews with coaches, and observations of games and practices. Lifetime and previous-30-day substance use was common among participants, and many were exposed to and had experienced various forms of violence. Keeping youths active helps prevent their joining gangs and using drugs. Youths from disadvantaged backgrounds are at a high risk for cancer because they are at greater risk for obesity and other adverse health-related conditions than are more affluent youths. Implementing and sustaining community programs for youths in public housing can reduce the effects of exposure to factors that put them at risk for cancer during adulthood: chronic poverty, lack of safe areas for recreation, easy access to alcohol and drugs, and exposure to violence. In addition, workshops to prevent substance use and violence and to teach leadership, sportsmanship, conflict resolution, and healthy youth development are needed for youths, coaches, and parents or guardians.


Recovery of myelin basic protein reactive T cells from spinal cords of Lewis rats with autoimmune encephalomyelitis.
Mononuclear cells were isolated from the spinal cords of 13 Lewis rats with clinical EAE induced by immunization with MBP in complete Freund's adjuvant. MBP-reactive lymphocytes were recovered from nine of these 13 SC-MNC populations by in vitro culture with MBP, followed by propagation of responding lymphocytes in IL 2-containing medium. T cell subset phenotype determination indicated a predominance of helper phenotype T cells in each of the two cultures examined. Clinical EAE was induced in naive Lewis rats by adoptive transfer of MBP-reactive lymphocytes recovered from three of these cultures.


Seasonal variation in the gas exchange characteristics of Primula species.
Seasonal dynamics of CO2 uptake are presented for three species of Primula native to the British Isles. Leaf photosynthetic rates were estimated in the field from the assimilation of 14CO2. Maximum photosynthetic rates showed a steady declineas the year passed in all three species but P. vulgaris displayed a peak in photosynthetic rate prior to canopy expansion which was not observed in the other species.Overwintered leaves of P. vulgaris photosynthesised at comparable rates to those of leaves at the end of the previous growing season. The carbon gain due to these overwintered leaves together with that from utilization of the high, spring light phase by the first formed leaves could result in a greater allocation of resources to flowering.Information from a comparison of light response curves measured at a similar developmental stage, in the field and the laboratory, allowed the species to be ranked according to their degree of shade tolerance; P. vulgaris greater than P. elatior greater than P. veris.


Efficacy and safety of secondary procedures for maintaining arteriovenous hemodialysis access patency: protocol for a systematic review and network meta-analysis.
Arteriovenous (AV) hemodialysis access creation is recommended by international guidelines as the preferred method of hemodialysis access. However, most AV access sites will require revision to maintain patency. Although several treatment options exist, many have not been directly compared. We intend to compare the relative effectiveness of methods to maintain post-intervention primary patency of failing AV access. We will search EMBASE, MEDLINE, CENTRAL, trial registries, the grey literature, and ancestry and citation search from January 1977 to present, for randomized controlled trials comparing interventions to maintain primary patency of AV access. Two investigators will independently and blindly review all identified citations and extract data from included studies. The primary outcome is the primary patency 6 months after intervention. Secondary outcomes include immediate technical and functional success, reinterventions, patency, and mortality. Risk of bias, subgroup analyses, and sensitivity analyses are planned. There are a number of treatment modalities for the management of failing AV access. However, most modalities have only been directly compared with plain old balloon angioplasty, and currently synthesized evidence focuses on individual pairwise comparisons. In light of the lack of comprehensively synthesized evidence and clinical equipoise, our study intends to synthesize currently available evidence though it is unclear which treatment modality is most effective. PROSPERO ID CRD42020148224.


Purification of pancreatic lipase via its affinity for bile salts and apolar surfaces.
An improved method for the purification of pancreatic lipase in milligram amounts is described. Only one batch step and one chromatographic step are required to produce a lipase-colipase complex and a lipase largely free of colipase. Both species are lipid free; physical and kinetic data indicate that the predominant lipase species is lipase B.


Association between discontinuation of benzodiazepine receptor agonists and post-operative delirium among inpatients with liaison intervention: A retrospective cohort study.
Several studies have investigated the association between benzodiazepine receptor agonist (BZDRA) use during the perioperative period and an elevated incidence of delirium. However, no study has focused on the time course of BZDRA use, including continuation, discontinuation, initiation, and no use. This study aimed to examine the influence of the time course of BZDRA use on post-operative delirium. This retrospective cohort study was conducted by reviewing medical records. We included patients who were scheduled for surgery under general anesthesia and had been referred to a liaison psychiatrist for pre-operative psychiatric assessment. The patients were classified into four groups based on the pre- and post-operative time course of oral BZDRA use, as follows: continuation, discontinuation, initiation, and no use (never used). The primary outcome was the prevalence of post-operative delirium in non-intensive care unit settings. We also performed stratified analyses according to age, the presence of cognitive impairment, the presence of delirium history, and antipsychotic drug use on admission. Among 250 patients, 78 (31%) developed post-operative delirium. The Discontinuation group had a higher rate of delirium (49%, 24/49) than the other groups (Continuation [14%, 4/29]; Initiation [38%, 3/8], Never used [29%, 47/164], p = 0.008). Abrupt discontinuation of BZDRAs during the perioperative period may be a risk factor for post-operative delirium and should therefore be avoided.


Ellipticity dependence of high-harmonic generation in solids originating from coupled intraband and interband dynamics.
The strong ellipticity dependence of high-harmonic generation (HHG) in gases enables numerous experimental techniques that are nowadays routinely used, for instance, to create isolated attosecond pulses. Extending such techniques to solids requires a fundamental understanding of the microscopic mechanism of HHG. Here we use first-principles simulations within a time-dependent density-functional framework and show how intraband and interband mechanisms are strongly and differently affected by the ellipticity of the driving laser field. The complex interplay between intraband and interband effects can be used to tune and improve harmonic emission in solids. In particular, we show that the high-harmonic plateau can be extended by as much as 30% using a finite ellipticity of the driving field. We furthermore demonstrate the possibility to generate, from single circularly polarized drivers, circularly polarized harmonics. Our work shows that ellipticity provides an additional knob to experimentally optimize HHG in solids.The mechanisms of high-order harmonic generation in bulk system and dilute gas are different. Here the authors use first-principle methods to explore the ellipticity dependence and control of the HHG in periodic solids by involving the interband and intraband dynamics in Si and MgO.


Laparoscopic cholecystectomy for acute cholecystitis: technical considerations and outcome.
Laparoscopic cholecystectomy (LC) is the preferred method of treatment for patients with gallbladder disease in the elective setting. Despite being technically more difficult, LC performed during the early course of acute cholecystitis can be safe and cost-effective. The current review discusses the diagnostic and therapeutic strategies that may help promote the safe and successful laparoscopic treatment of patients with acute cholecystitis.


Endothelin receptor B enhances liver injury and pro-inflammatory responses by increasing G-protein-coupled receptor kinase-2 expression in primary biliary cholangitis.
Severe diseases like cirrhosis and liver failure can be developed from primary biliary cholangitis (PBC). Endothelin-2 (EDN2) and endothelin receptor B (EDNRB) are related to the pathogenesis of PBC. However, the roles of EDN2 and EDNRB in PBC-related liver injury and inflammation along with molecular mechanisms are poorly defined. In this study, histopathologic alterations of liver tissues were assessed through hematoxylin-eosin staining. Alanine transaminase (ALT), alkaline phosphatase (ALP), aspartate transaminase (AST), and γ-Glutamyltranspetidase (GGT) (4 liver function indexes) serum levels were detected with corresponding activity assay kits. Also, we determined the levels of M2 subtype anti-mitochondrial antibody (AMA-M2), interferon-gamma (IFN-γ), and tumor-necrosis factor alpha (TNFα) in serum with ELISA assay. Later, RT-qPCR assay was used to measure the expression of genes at mRNA levels, while western blotting and immunohistochemical techniques were used to detect protein levels of genes. Our results showed that the liver tissues of PBC patients and mice presented with severe hepatocyte injury and inflammatory cell infiltration as well as destruction of intrahepatic small bile ducts. ALP, AST, ALT, GGT, AMA-M2, IFN-γ, and TNF-α serum levels were higher in PBC patients and mice. Besides, EDN2 and EDNRB were highly expressed in serums and livers of PBC patients and mice. EDNRB potentiated PBC-related liver injury and pro-inflammatory responses, as evidenced by observation of serious liver pathologic injury and increased serum levels of ALP, AST, ALT, AMA-M2, IFN-γ, and TNF-α in PBC mice following EDNRB overexpression. EDNRB overexpression or activation via its agonist IRL-1620 TFA triggered liver injury and pro-inflammatory responses, increased GRK2 expression and induced NF-κB expression and activation in wild-type mice. EDNRB knockdown or inhibition by Bosentan alleviated liver damage and inflammation, reduced GRK2 expression, and inhibited NF-κB in PBC mice. These findings suggested EDNRB loss or inhibition weakened liver injury and pro-inflammatory responses by down-regulating GRK2 and inhibiting the NF-κB pathway in PBC mice.


Improved positron emission tomography imaging of glioblastoma cancer using novel 68Ga-labeled peptides targeting the urokinase-type plasminogen activator receptor (uPAR).
The urokinase-type plasminogen activator receptor (uPAR) is overexpressed in several cancers including glioblastoma (GBM) and is an established biomarker for metastatic potential. The uPAR-targeting peptide AE105-NH2 (Ac-Asp-Cha-Phe-(D)Ser-(D)Arg-Tyr-Leu-Trp-Ser-CONH2) is a promising candidate for non-invasive positron emission tomography (PET) imaging of uPAR. Despite the optimal physical properties of 68Ga for peptide-based PET imaging, low tumor uptakes have previously been reported using 68Ga-labeled AE105-NH2-based tracers. In an attempt to optimize the tumor uptake, we developed three novel tracers with alkane (AOC) and polyethylene glycol (PEG) spacers inserted between AE105-NH2 and the radio metal chelator 2-(4,7-bis(carboxymethyl)-1,4,7-triazonan-1-yl)pentanedioic acid (NODAGA). The resulting tracers NODAGA-AOC-AE105-NH2, NODAGA-PEG3-AE105-NH2 and NODAGA-PEG8-AE105-NH2 were compared to the non-spacer version, NODAGA-AE105-NH2. Following radiolabeling with 68Ga, we evaluated the in vitro and in vivo performance in mice bearing subcutaneous tumors derived from the uPAR-expressing human GBM cell line U87MG. In vivo PET/CT imaging showed that introduction of PEG spacers more than doubled the in vivo tumor uptake after 1 h compared with the non-spacer version: 68Ga-NODAGA-PEG3-AE105-NH2 (2.08 ± 0.37%ID/g) and 68Ga-NODAGA-PEG8-AE105-NH2 (2.01 ± 0.22%ID/g) vs. 68Ga-NODAGA-AE105-NH2 (0.70 ± 0.40%ID/g), p < 0.05. In addition, 68Ga-NODAGA-PEG8-AE105-NH2 showed significantly higher (p < 0.05) tumor-to-background contrast (3.68 ± 0.23) than the other tracers. The specific tumor-targeting property of 68Ga-NODAGA-PEG8-AE105-NH2 was established by effectively blocking the tumor uptake with co-injection of unlabeled AE105-NH2 (1 h: unblocked 2.01 ± 0.22%ID/g vs. blocked 1.24 ± 0.09%ID/g, p < 0.05). Ex vivo biodistribution confirmed the improved tumor uptakes of the PEG-modified tracers. 68Ga-NODAGA-PEG8-AE105-NH2 is thus a promising candidate for human translation for PET imaging of GBM.


The association between oral candidiasis and severity of chemoradiotherapy-induced dysphagia in head and neck cancer patients: A retrospective cohort study.
Concurrent chemoradiotherapy (CCRT) for head and neck cancer (HNC) is a risk factor for oral candidiasis (OC). As Candida spp. are highly virulent, we conducted a retrospective study to determine whether OC increases the severity of dysphagia related to mucositis in HNC patients. We retrospectively analyzed the cases of consecutive patients with carcinomas of the oral cavity, pharynx, and larynx who underwent CCRT containing cisplatin (CDDP) at our hospital. The diagnosis of OC was based on gross mucosal appearance. We performed a multivariate analysis to determine whether OC was associated with the development of grade 3 dysphagia in the Radiation Therapy Oncology Group (RTOG) Acute Toxicity Criteria. The maximum of the daily opioid doses was compared between the patients with and without OC. We identified 138 HNC patients. OC was observed in 51 patients (37%). By the time of their OC diagnosis, 19 (37%) had already developed grade 3 dysphagia. Among the 30 patients receiving antifungal therapy, 12 (40%) showed clinical deterioration. In the multivariate analysis, OC was independently associated with grade 3 dysphagia (OR 2.75; 95%CI 1.22-6.23; p = 0.015). The patients with OC required significantly higher morphine-equivalent doses of opioids (45 vs. 30 mg/day; p = 0.029). Candida infection causes refractory dysphagia. It is worth investigating whether antifungal prophylaxis reduces severe dysphagia related to candidiasis.


pH-sensitive polyelectrolyte complex gel microspheres composed of chitosan/sodium tripolyphosphate/dextran sulfate: swelling kinetics and drug delivery properties.
Porous chitosan (CS) polyelectrolyte complex (PEC) hydrogel microspheres were prepared via either wet phase-inversion or ionotropic crosslinking with sodium tripolyphosphate (Na+ - TPP) and dextran sulfate (DS). The resulting microspheres were characterized using scanning electron microscopy (SEM) and elemental analysis (EA). The controlled release behavior of ibuprofen (IBU) from these microspheres was investigated. The PEC microspheres were about 700-950 microm in diameter with large pores and open porous structure. The CS/TPP/DS microspheres resisted hydrolysis in strong acid and biodegradation in enzymatic surroundings. The swelling kinetics for CS microspheres was close to Fickian diffusion, whereas those for CS/TPP and CS/TPP/DS were non-Fickian. Furthermore, the equilibrium water content (EWC) and water diffusion coefficient (D) increased with the pH of the media. The release profiles of IBU from CS/TPP/DS microspheres were slow in simulated gastric fluid (SGF, pH 1.4) over 3 h, but nearly all of the initial drug content was released in simulated intestinal fluid (SIF, pH 6.8) within 6 h after changing media. Overall the results demonstrated that CS/TPP/DS microspheres could successfully deliver a hydrophobic drug to the intestine without losing the drug in the stomach, and hence could be potential candidates as an orally administered drug delivery system.


High-Performance Reversible Furan-Maleimide Resins Based on Furfuryl Glycidyl Ether and Bismaleimides.
Two reversible furan-maleimide resins, in which there are rigid -Ph-CH2-Ph- structures and flexible -(CH2)6- structures in bismaleimides, were synthesized from furfuryl glycidyl ethers (FGE), 4,4'-diaminodiphenyl ether (ODA), N,N'-4,4'-diphenylmethane-bismaleimide (DBMI), and N,N'-hexamethylene-bismaleimide (HBMI). The structures of the resins were confirmed using Fourier transform infrared analysis, and the thermoreversibility was evidenced using differential scanning calorimetry (DSC) analysis, as well as the sol-gel transformation process. Mechanical properties and recyclability of the resins were preliminarily evaluated using the flexural test. The results show the Diels-Alder (DA) reaction occurs at about 90 °C and the reversible DA reaction occurs at 130-140 °C for the furan-maleimide resin. Thermally reversible furan-maleimide resins have high mechanical properties. The flexural strength of cured FGE-ODA-HBMI resin arrives at 141 MPa. The resins have a repair efficiency of over 75%. After being hot-pressed three times, two resins display flexural strength higher than 80 MPa.


Heavy metal contamination along different tidal zones of a tropical Bay of Bengal coastal environment influenced by various anthropogenic activities.
The spatiotemporal variations of five heavy metals (Cd, Cu, Cr, Pb, and Zn) in the beach sediments along the Tamil Nadu coast sourced from various anthropogenic activities were assessed using atomic absorption spectrophotometry (AAS). Various pollution monitoring indices were computed to clearly understand the metal pollution status along the Tamil Nadu coastline. The metal concentrations in sediments were typically higher in the summer season than in the monsoon season. In the monsoon season, metal concentration followed a decreasing order of Zn > Cr > Cu > Pb > Cd, and in the summer season, the order was Cr > Zn > Cu > Pb > Cd. During the monsoon season, freshwater runoff from the rainfall dilutes the sediments and their trace element load. However, due to a lack of freshwater influx during the summer season, the heavy metals in the sediments get concentrated and showed elevated levels. Geo-accumulation index, ecological risk index, pollution load index, and contamination degree clearly depict that Cd and Pb have higher accumulation and pose greater hazard when compared with other metals. The rivers flowing in the region also transport the heavy metals from the mainland to the estuaries and coastal environments. Metal levels along the Tamil Nadu coast are influenced by various anthropogenic activities persistent along the coastline. Some of the activities that cause metal contamination are mining, milling, electroplating, furnishing, pharmaceutical industries, fishing, harbor activities, urban runoff, and agricultural runoff, which release a variety of toxic metals into the coastal environment.


Amplitude of somatosensory cortical evoked potentials is correlated with spontaneous activity of spinal neurones in the cat.
Simultaneous recordings of cortical evoked potentials in the posterior sigmoid gyrus, and spontaneous negative cord dorsum potentials (CDPs) of the L6 lumbar spinal segment, were made in the anaesthetised cat. The electrodes were positioned in cortical and spinal somatosensory regions where the largest spontaneous and evoked negative potentials were detected. Evoked potentials were produced by electrical stimulation to cutaneous nerves or by mechanical stimulation of the hindpaw skin. We found that both electrically and mechanically cortical evoked potentials were facilitated during the spontaneous negative CDPs. The magnitude of such facilitation was proportional to the amplitude of the 'conditioning' spontaneous negative CDPs. This led to a high positive correlation between amplitude fluctuations of spontaneous negative CDPs and fluctuations of the cortical evoked potentials. This observation suggests that transmission of cutaneous sensory information in ascending pathways could be facilitated when dorsal horn spinal neurones are active.


Characterization of ecto-ATPase on human blood cells. A physiological role in platelet aggregation?
Ecto-ATPase (EC 22.214.171.124) is a plasma membrane-bound enzyme which degrades extracellular triphosphate nucleotides. Although its physiological function is still unclear, the enzyme obscures the study of P2 purinoceptors (i.e. receptors for ATP and other di- and triphosphate nucleotides), since it is capable of metabolizing the pharmacological ligands, such as ATP, for these receptors. We characterized the ecto-ATPase activity on human blood cells with a [gamma 32P]ATP assay and HPLC measurements. We also determined whether ecto-ATPase activity could affect the anti-aggregatory role of ATP in whole human blood. The Km for ATP of the ecto-ATPase on human blood cells was 8.5 +/- 2.3 microM and the maximum degradation rate, at 37 degrees, was 2.7 +/- 1.1 nmol ATP/(min x mL whole blood). In whole blood the major part of ATP was broken down by the blood cells, predominantly by the leukocytes. ATP and UTP were broken down equally well, mainly yielding the corresponding di- and monophosphates. In search of inhibitors for the ecto-ATPase, we studied several analogs of ATP. 8-Bromo-ATP as well as 2'- and 3'-deoxy-ATP were substrates for the enzyme. In contrast, modification of the phosphate side chain yielded inhibitors. Subsequently, a possible role of the ecto-ATPase in platelet aggregation was verified. To assess the role of the plasma membrane-bound enzyme, platelet aggregation was determined in whole blood instead of platelet-rich plasma. In the presence of ATP alone, an antagonist of ADP-induced platelet aggregation, some aggregation was still observed. As breakdown of ATP by the ecto-ATPase leads to gradual formation of ADP, as mentioned above, we compared the effects of a stepwise versus bolus addition of ADP. Subsequent dosing of ADP (1.5, 2.5, 5 and 10 microM) resulted in platelet aggregation but to a much smaller extent, at most approximately 60%, compared to the amount of platelet aggregation obtained with a bolus addition of ADP (10 microM). In conclusion, human blood cells possess a high affinity ecto-ATPase which degrades ATP as well as ATP analogs with modified base and ribose moieties. ATP analogs with a modified phosphate chain are inhibitors of the ecto-ATPase. A direct role of the ecto-ATPase activity on platelet aggregation is probably small, as degradation of ATP to ADP proceeds slowly and cumulative addition of ADP to platelets in whole blood results in a modest amount of aggregation.(ABSTRACT TRUNCATED AT 400 WORDS)


Why are estrogen-receptor-negative breast cancers more aggressive than the estrogen-receptor-positive breast cancers?
It is well established that some of the hormone-resistant breast cancers lack functional estrogen receptor (ER) and exhibit a more aggressive metastatic phenotype. The estrogen activation of ER in ER-positive breast cancers enhances their aggressiveness, while the activation of exogenously introduced ERs into aggressive ER-negative cells diminishes their aggressiveness. The basis of the protective effect of the ER appears complex and could be due to the altered expression of genes involved in cell proliferation, differentiation and invasiveness. In this review, we propose different mechanisms for the higher aggressiveness of most of the ER-negative breast cancers.


Longitudinal Care Improves Cessation in Smokers Who Do Not Initially Respond to Treatment by Increasing Cessation Self-Efficacy, Satisfaction, and Readiness to Quit: A Mediated Moderation Analysis.
The Tobacco Longitudinal Care study was a randomized controlled trial for smoking cessation. It demonstrated that longitudinal care for smoking cessation, in which telephone-based counseling and nicotine replacement therapy were offered for 12 months, was more effective than the standard 8-week treatment. This study aims to identify for whom and how longitudinal care increased the likelihood of abstinence. Mediated moderation analyses were utilized across three time points. There was a trend towards smokers who did not respond to treatment (i.e., were still smoking) by 21 days being more likely to be abstinent at 6 months if they received longitudinal care rather than usual care. Similarly, those who did not respond to treatment by 3 months were more likely to be abstinent at 12 months if they received longitudinal care. At both time points, the likelihood of abstinence did not differ across treatment conditions among participants who responded to treatment (i.e., quit smoking). The effect on 6-month outcomes was mediated by satisfaction and readiness to quit. Cessation self-efficacy, satisfaction, and readiness to quit mediated the effect on 12-month outcomes. The effect of treatment condition on the likelihood of abstinence at 18 months was not moderated by response to treatment at 6 months. Smokers who did not respond to initial treatment benefited from longitudinal care. Differential effects of treatment condition were not observed among those who responded to early treatment. Conditional assignment to longitudinal care may be useful. Determining for whom and how interventions work over time will advance theory and practice.


How time in the US and race/ethnicity shape food parenting practices and child diet quality.
Childhood obesity prevalence is high among children from immigrant/refugee households who live in high-income countries. Poor child dietary intake is a critical risk factor for elevated obesity prevalence and food parenting practices have been found to be associated with child dietary intake and eating behaviors. The main aim of this study was to examine the associations between migrants'/refugees' food parenting practices, the length of residence time in the US, race/ethnicity, and child diet quality. The current study included 577 families from three racial/ethnic groups that include mostly foreign-born parents (Latino, Hmong, and Somali/Ethiopian), and a comparison group of 239 non-Hispanic White families. Results showed that for Latino and Hmong parents, some food parenting practices varied by how long they had lived in the US. For example, more recently moved parents engaged in more non-directive (e.g., avoid buying sweets) practices compared with US-born parents. In contrast, Somali/Ethiopian parents engaged in different food parenting practices than White parents, regardless of time in the US. Results also showed that diet quality among Hmong children was lower if their parents were US-born compared to foreign-born. Future researchers may want to consider studying why some food parenting practices change when parents move to the US and explore whether there is a combination of food parenting practices that are most useful in promoting a healthful child's diet and weight among immigrant and refugee families.


The advanced life support base hospital audit for medical control in an emergency medical services system.
A large California county uses an audit of its advanced life support (ALS) base hospitals to maintain medical control of prehospital care and to improve the county emergency medical services. The audit is a rigorous, semi-annual evaluation of ALS base hospital performance using objective, written criteria. The county emergency medical service district and the base hospitals have benefited from the data that have resulted from the audits. The base hospital audit is an excellent method of assessing medical control in an emergency medical services system.


Real-Time Monitoring of Grazing Cattle Using LORA-WAN Sensors to Improve Precision in Detecting Animal Welfare Implications via Daily Distance Walked Metrics.
Animal welfare monitoring relies on sensor accuracy for detecting changes in animal well-being. We compared the distance calculations based on global positioning system (GPS) data alone or combined with motion data from triaxial accelerometers. The assessment involved static trackers placed outdoors or indoors vs. trackers mounted on cows grazing on pasture. Trackers communicated motion data at 1 min intervals and GPS positions at 15 min intervals for seven days. Daily distance walked was determined using the following: (1) raw GPS data (RawDist), (2) data with erroneous GPS locations removed (CorrectedDist), or (3) data with erroneous GPS locations removed, combined with the exclusion of GPS data associated with no motion reading (CorrectedDist_Act). Distances were analyzed via one-way ANOVA to compare the effects of tracker placement (Indoor, Outdoor, or Animal). No difference was detected between the tracker placement for RawDist. The computation of CorrectedDist differed between the tracker placements. However, due to the random error of GPS measurements, CorrectedDist for Indoor static trackers differed from zero. The walking distance calculated by CorrectedDist_Act differed between the tracker placements, with distances for static trackers not differing from zero. The fusion of GPS and accelerometer data better detected animal welfare implications related to immobility in grazing cattle.


Cultures of resistance? A Bourdieusian analysis of doctors' antibiotic prescribing.
The prospect of an 'antimicrobial perfect storm' in the coming decades through the emergence and proliferation of multi-resistant organisms has become an urgent public health concern. With limited drug discovery solutions foreseeable in the immediate future, and with evidence that resistance can be ameliorated by optimisation of prescribing, focus currently centres on antibiotic use. In hospitals, this is manifest in the development of stewardship programs that aim to alter doctors' prescribing behaviour. Yet, in many clinical contexts, doctors' antibiotic prescribing continues to elude best practice. In this paper, drawing on qualitative interviews with 30 Australian hospital-based doctors in mid-2013, we draw on Bourdieu's theory of practice to illustrate that 'sub-optimal' antibiotic prescribing is a logical choice within the habitus of the social world of the hospital. That is, the rules of the game within the field are heavily weighted in favour of the management of immediate clinical risks, reputation and concordance with peer practice vis-à-vis longer-term population consequences. Antimicrobial resistance is thus a principal of limited significance in the hospital. We conclude that understanding the habitus of the hospital and the logics underpinning practice is a critical step toward developing governance practices that can respond to clinically 'sub-optimal' antibiotic use.


The role of animals in our perception of people.
Objective evidence is beginning to confirm the popular belief that people are often judged by the way they interact with animals. This phenomenon is reviewed in the context of social and cognitive psychology and suggestions are offered for future research.