Novel imaging technology and procedures for studying brain function in preadolescent awake marmosets.
Novel imaging technology and procedures were developed to study brain function in preadolescent awake marmosets never exposed to anesthesia. A radiofrequency transmit and receive, head only volume coil was designed and integrated into a holding system. An acclimation procedure was developed without the use of anesthesia or sedation that allowed for awake imaging. Preadolescent 8-month old male and female marmosets were imaged for resting state BOLD functional connectivity to assess the status of the default mode network. Levels of reactivity during acclimation sessions and behavioral stress following imaging were assessed. Data on functional coupling in the default mode network suggest the organization of connectivity to the prefrontal cortex is not fully developed at 8 months of age. The stress associated with the imaging procedure is comparable to that observed when marmosets are removed from their home cage and temporarily isolated from the family. The design of the radiofrequency coil provides B1 homogeneity across the entire brain without signal drop off. The unique design of the head cradle obviates the need for any stabilizing surgery, ear bars or bite bar and could be adapted to any size marmoset. The acclimation requires no anesthesia or sedation at any time in the early life of the developing marmoset, a condition that better reflects the human experience. A method is provided for imaging functional activity in the brain of fully awake preadolescent marmosets without any history of anesthesia or sedation.


Assessment of the patient with cleft lip and palate. A developmental approach.
Children with cleft lip and palate require interdisciplinary team care from infancy through adolescence. An understanding of developmental stages allows the cleft palate team to adapt and integrate its services into the rapidly changing life of the child. This article discusses the maturational, developmental stages of childhood and the services the child with cleft lip and palate and the child's family deserve through each stage. Health care providers in all settings may continue to provide appropriate care for all patients with cleft lip and palate, despite the challenges of a changing health care environment, by emphasizing the needs of the child in all developmental stages.


The association of water to cellulose and hemicellulose in paper examined by FTIR spectroscopy.
The nature of water sorption to different materials has always been a complex matter to address, partly due to the different possibilities of hydrogen-bond formation. For cellulosic materials this is extremely important for its product performance. In order to gain a deeper understanding of the moisture adsorption mechanisms of cellulose and hemicelluloses, the molecular interaction between moisture and paper and between moisture and some wood polymers was studied using FTIR spectroscopy under stable humid conditions. It was found that all the moisture-sorbing sites adsorbed moisture to the same relative degree, and that the rate of adsorption was the same for all these sites. It was also noticed that the moisture is adsorbed in the form of clusters. A direct relationship was found between the moisture weight gain and the increase in the absorbance peaks for humidities up to 50% relative humidity after which the moisture gain increased faster, a fact that still remains to be explained.


Correction to: Morphine Induces Apoptosis, Inflammation, and Mitochondrial Oxidative Stress via Activation of TRPM2 Channel and Nitric Oxide Signaling Pathways in the Hippocampus.
The original version of this article unfortunately contained some mistake.


Technological intervention for obese patients with type 2 diabetes.
This study applied a 6-month educational intervention that used the technology of the short message service (via cellular phones) and the Internet for obese patients with type 2 diabetes. Eighteen patients were randomly assigned to an intervention group and 16 were assigned to a control group (N = 34). Patients in the intervention group were asked to access a web site by using personal cellular phones or computer Internet services to input their blood glucose levels daily. Participants were then sent optimal recommendations via cellular phone and the Internet weekly. After 6 months, the intervention group had a statistically significant decrease in glycosylated hemoglobin, fasting plasma glucose, 2-hour postmeal glucose, and total cholesterol, as compared with the control group.


Efficacy of a putative GABA analog on synaptic transmission in the cat spinal cord.
4-Hydroxy-4-phenylcaproamide (HPhCA), at high doses or rates of IV injection depressed the ventral root reflexes elicited by nerve or dorsal root stimulation. The D (direct) and I (synaptic) ventral root waves and the antidromic (A) dorsal root wave evoked by intraspinal stimulation were also depressed. Similar effects were produced when HPhCA was applied topically on the cord dorsum. At 80 mg/kg and 8 mg/kg/min, the spinal reflexes and the I wave were facilitated for 4 to 6 h, but the D and A waves were depressed. Intracellular recordings from motoneurons showed that HPhCA injection produced: hyperpolarization that lasted several hours, short lasting (< 20 min) facilitation of both EPSPs and IPSPs as well as spike-like potentials (SLPs) that were triggered by EPSPs even though the neuron was hyperpolarized. SLPs may reach the threshold for full spikes. Our results suggest that the spinal depression results from hyperpolarization of motoneurons and the initial facilitation appears to be presynaptic. The late facilitation may be produced by SLPs. HPhCA does not appear to mimic the actions of GABA in primary afferents fibers and motoneurons.


Preoperative Optimization of Promotility in Robotic Prostatectomy and Minimally Invasive Kidney Surgery.
Patients are routinely discharged postoperative day 1 following minimally invasive surgery (MIS) for prostate cancer and kidney cancer. Delays in discharge are often related to gastrointestinal symptoms such as nausea, abdominal pain and vomiting; however, the role of baseline constipation in these symptoms and resultant delays in discharge is unclear. We conducted a prospective observational study to describe the incidence of baseline constipation among patients undergoing MIS prostate and kidney surgery, and its relationship to length of stay (LOS). Consenting adult patients undergoing MIS procedures for kidney and prostate cancer completed constipation symptom questionnaires perioperatively. Clinicopathological data were collected prospectively. Delay in discharge, defined as LOS >2 days, was the primary outcome. Patients were stratified by the primary outcome and preoperative Patient Assessment of Constipation Symptoms (PAC-SYM) scores were compared. A total of 97 patients enrolled, of whom 29 underwent radical nephrectomy, 34 underwent robotic partial nephrectomy and 34 underwent robotic prostatectomy. Constipation symptoms were reported in 67/97 patients (69%). A total of 17/97 patients (18%) had a delay in discharge. Patients who discharged on time had a median PAC-SYM score of 2 (IQR 2-9) compared to 4 (IQR 0-7.5) for those with a delay (p=0.021). Patients who had a delay with gastrointestinal symptoms had a median PAC-SYM score of 5 (IQR 1.5-11.5, p=0.032). Seven out of 10 patients undergoing routine MIS procedures report constipation symptoms, which may represent a target for preoperative interventions to reduce LOS after surgery.


A 5 1/2 year experience with the St. Jude Medical cardiac valve prosthesis. Early and late results of 737 valve replacements in 671 patients.
Between June 12, 1978, and June 12, 1983, 737 St. Jude Medical valves were implanted in 671 patients (431 males, 240 females) ranging in age from 9 months to 82 years (mean 55 years); 16 of these patients (2.3%) were less than or equal to 15 years and 82 (12.2%) were greater than or equal to 70 years. Associated procedures were performed in 28.2% of the 500 aortic valve replacements, 13.3% of the 105 mitral valve replacements, and 10.6% of the 66 double mitral and aortic valve replacements. Hospital mortality (less than or equal to 30 days) was 3.6% (18/500 patients) for aortic, 4.7% (5/105 patients) for mitral, and 0% for double valve replacement. Only one of these 23 hospital deaths was possibly valve-related. Complete follow-up was achieved during December, 1983, and January, 1984, to provide a minimum follow-up of 6 months. Follow-up has been 100% for a total of 1,619 patient-years, with a mean follow-up of 2 1/2 years. There were 41 late deaths (6.1%): 30 in the aortic group, eight in the mitral group, and three in the double valve replacement group. Fourteen (34.2%) of these late deaths have been considered valve-related. At 5 1/2 years, the actuarial survival rate, hospital mortality excluded, is 91% for aortic, 90% for mitral, and 95% for double valve replacement. Functional improvement of these patients is quite satisfactory: Preoperatively, 60.3% were in Class III or IV of the New York Heart Association, whereas postoperatively, 99.5% of the patients are in Class I or II. As 78 patients (65 aortic, 10 mitral, and three double valve replacement) did not receive anticoagulation therapy for a total period of 84 patient-years, the incidence of valve thrombosis, systemic embolism, and sudden or suspicious deaths in this group was compared with that in a group of 630 patients (including 60 patients from the first group who were given anticoagulants afterwards) subjected to long-term anticoagulation for a total period of 1,535 patient-years. A significantly higher incidence of valve thrombosis and systemic embolism was observed in the absence of anticoagulation. Anticoagulant-related complications occurred in 10 patients, with an incidence of 0.65/100 patient-years. On the basis of this 5 1/2 years of experience, the St. Jude Medical valve appears to be an excellent mechanical prosthesis for cardiac valve replacement, in terms of hemodynamic performance and low thrombogenicity, in patients receiving anticoagulants.


Metabolic reprogramming by dual-targeting biomimetic nanoparticles for enhanced tumor chemo-immunotherapy.
Cancer-associated fibroblasts (CAFs)-mediated metabolic support plays a vital role in tumorigenesis. The metabolic network between cancer cells and CAFs may serve as promising targets for cancer therapy. Here, aiming at targeted blockade of the metabolic support of CAFs to cancer cells, a biomimetic nanocarrier is designed by coating solid lipid nanoparticles containing chemotherapeutic paclitaxel (PTX) and glycolysis inhibitor PFK15 with hybrid membranes of cancer cells and activated fibroblasts. The nanoparticles possess outstanding dual-targeting ability which can simultaneously target cancer cells and CAFs. The encapsulated glycolysis inhibitor PFK15 can prevent the glycolysis of cancer cells and CAFs at the same time, thus increasing the chemosensitivity of cancer cells and blocking the metabolic support of CAFs to cancer cells. The results showed that the combination of PTX and PFK15 exhibited synergistic effects and inhibited tumor growth effectively. Moreover, the biomimetic nanoparticles obviously reduced the lactate production in the tumor microenvironment, leading to activated immune responses and enhanced tumor suppression. This work presents a facile strategy to destroy the metabolic network between cancer cells and CAFs, and proves the potential to elevate chemo-immunotherapy by glycolysis inhibition. STATEMENT OF SIGNIFICANCE: In many solid tumors, most cancer cells produce energy and carry out biosynthesis through glycolysis, even in aerobic conditions. As the main tumor stromal cells, cancer-associated fibroblasts (CAFs) usually turn oxidative phosphorylation into aerobic glycolysis with metabolic reprogramming and provide high-energy glycolytic metabolites for cancer cells. The metabolic network between cancer cells and CAFs is regarded as the vulnerability among cancer cells. Moreover, lactate produced by cancer cells and CAFs through glycolysis often leads to the immunosuppressive tumor microenvironment. The present study provides an effective approach to destroy the metabolic network between cancer cells and CAFs and greatly improves the antitumor immune response by reducing lactate production, which serves as a promising strategy for combined chemo-immunotherapy mediated by glycolysis.


Ergothioneine inhibits the progression of osteoarthritis via the Sirt6/NF-κB axis both in vitro and in vivo.
Osteoarthritis (OA), which is a major cause of serious arthralgia and disability among the elderly, has long plagued numerous populations. However, the specific molecular mechanisms involved in the etiology of OA are unclear. SIRT6 plays a critical function in the development of several inflammatory and aging-associated diseases. A study by D'Onofrio demonstrates that ergothioneine (EGT) is an effective activator of SIRT6. As revealed by previous reports, EGT exerts beneficial effects on the mouse body, including resistance to oxidation, tumor, and inflammation. Therefore, this work attempted to identify the inflammatory resistance of EGT and explore its effects on the incidence and development of OA. Mouse chondrocyte stimulation using varying levels of EGT and 10 ng/mL IL-1β. According to in vitro experiments, EGT significantly reduced the decomposition of collagen II and aggrecan in OA chondrocytes, as well as inhibited the overexpression of PGE2, NO, IL-6, TNF-α, iNOs, COX-2, MMP-13, and ADAMTS5. In the present work, EGT hindered the NF-κB activity by activating the SIRT6 pathway in OA chondrocytes, which in turn, significantly attenuated the inflammatory response resulting from IL to 1β. The inhibitory effect of EGT on the progression of OA was demonstrated by the mouse DMM model experiment. Thus, this study revealed that EGT was effective in anti-OA treatment.


Relationship between lymphopenia and disease activity in persons with multiple sclerosis treated with dimethyl fumarate.
Dimethyl fumarate (DMF) is a disease-modifying therapy (DMT) used to treat relapsing multiple sclerosis (MS). Its precise mechanism in treating MS involves nuclear factor erythroid-derived 2-related factor-dependent and -independent pathways. Lymphopenia, defined according to NIH Common Terminology for Adverse Events v5.0, is one potential adverse effect. It is unclear whether lymphopenia correlates with disease activity; existing studies have yielded conflicting results. To determine whether lymphopenia in DMF-treated persons with MS (PwMS) correlates with disease activity. A retrospective chart review of 66 PwMS treated with DMF between January 1, 2013 and September 30, 2020. Participants who experienced lymphopenia were older (p < 0.001), and had a longer disease duration (p = 0.012) and lower baseline absolute lymphocyte count (ALC) (p < 0.001). Breakthrough disease activity was the most common reason for DMF discontinuation (53.0%). Lymphopenia occurred in 36.4%, with ALCs decreasing over the first 12 months of therapy before plateauing. Lymphopenia was associated with a trend towards reduced relapses (p = 0.059) and significantly improved MRI activity (p = 0.001) and no evidence of disease activity (NEDA-3) (p = 0.022), but not disability progression (p = 0.549). Persons with lymphopenia were significantly less likely to be treated with another DMT after DMF (p = 0.036). Risk factors for and rates of lymphopenia resembled existing data. Lymphopenia was associated with significantly improved MRI activity and achievement of NEDA-3, and whether PwMS were treated with another DMT after DMF. Further studies are required to clarify the mechanism of DMF, lymphocyte subsets and their relationship with disease activity, and which characteristics predict response to DMF.


Dysfunctional attitudes or extreme response style as predictors of depressive relapse and recurrence after mobile cognitive therapy for recurrent depression.
According to previous research, dysfunctional attitudes and/or scoring extreme on the end-point anchors of questionnaires of dysfunctional thinking predict depressive relapse/recurrence. Evidence that these two methods represent a risk for depressive relapse/recurrence is however mixed, due to differential or poorly defined concepts. The current study aimed to test the two methods. Remitted recurrently depressed patients with low residual depressive symptoms (N = 264) were recruited as part of a randomized controlled trial of the effectiveness of mobile Cognitive Therapy for recurrent depression versus treatment as usual. In the current secondary analysis, Cox regression models were conducted to test dysfunctional attitudes and extreme responding variables (assessed on the Dysfunctional Attitudes Scale [DAS]) as predictors of depressive relapse/recurrence within two years after randomization. Data from 255 participants were analyzed. Results showed that DAS total scores at baseline significantly predicted depressive relapse/recurrence (Hazard Ratio [HR] = 1.01, p = .042). An index that reflects endorsement of habitual relative to functional responses was a significant predictor of depressive relapse/recurrence (HR = 2.11, p = .029). The current study employed a single measure to identify extreme responses and dysfunctional attitudes. Secondly, various statistical analyses were performed without correcting for multiple testing, which in turn increased the likelihood to finding significant results. Current study confirmed both methods: People who scored higher on the DAS or had relatively more habitual than functional responses on the extreme positive ends of the DAS had a decreased time to depressive relapse/recurrence.


Tityus serrulatus Hypotensins: a new family of peptides from scorpion venom.
Using a proteomic approach, a new structural family of peptides was put in evidence in the venom of the yellow scorpion Tityus serrulatus. Tityus serrulatus Hypotensins (TsHpt) are random-coiled linear peptides and have a similar bradykinin-potentiating peptide (BPP) amino acid signature. TsHpt-I (2.7kDa), the first member of this family, was able to potentiate the hypotensive effects of bradykinin (BK) in normotensive rats. Using the C-terminal of this peptide as a template, a synthetic analog peptide (TsHpt-I([17-25])) was designed to held the BK-potentiating effect. A relevant hypotensive effect, independent on BK, was also observed on both TsHpt (native and synthetic). To better evaluate this hypotensive effect, we examined the vasorelaxation of aortic rings from male Wistar rats and the peptides were able to induce endothelium-dependent vasorelaxation dependent on NO release. Both TsHpt could not inhibit ACE activity. These peptides appear to exert their anti-hypertensive effect through NO-dependent and ACE-independent mechanisms.


Venous ligation-mediated bone adaptation is NOS 3 dependent.
Interstitial fluid flow (IFF) in bone has been hypothesized to mediate bone modeling in the absence of mechanical strain. The mechanism of this effect has not been clearly defined, though previous studies indicate that nitric oxide (NO) may play an important role in mediating IFF. In the current study, mice with a targeted disruption of the NOS 3 gene were used according to a previously established model of altered interstitial fluid flow in bone. Femoral vein ligation was performed in one limb to increase intramedullary pressure and consequently its IFF; a sham operation was performed on the contralateral limb. The mice were then hindlimb suspended to uncouple the effects of altered flow in the limb from mechanical loading. Differences in radiographic bone density and bone strength were compared for the sham and venous-ligated femurs in wild-type (WT) mice and NOS 3 knockout (KO) mice. Suspension-induced bone loss in the femurs, as evidenced by a loss in radiographic bone mineral density (BMD), was seen in both groups. Differences between sham and venous-ligated femurs were significant only for the WT mice, in which there appeared to be a protective effect of venous ligation against bone loss [-6.69% (ligated) vs. -12.36% (sham), P<0.05]. Furthermore, the difference in bone density between sham and venous-ligated femurs was muted by NOS 3 knockout, suggesting that the protective effect of venous ligation against bone loss observed in the WT group was NO dependent. The differences in relative BMD were mirrored in the mechanical testing experiments, where maximum load to fracture was significantly higher in the venous-ligated limbs relative to the sham limbs of the WT mice, but not in the NOS 3 group. Taken together, these data further support the hypothesis that fluid flow can modulate bone modeling and suggest that IFF-mediated bone adaptation is NOS 3 dependent.


Modification of VTMS hybrid monolith via thiol-ene click chemistry for capillary electrochromatography.
An n-octadecanethiol (C(18))/3-mercapto-1-propane-sulfonate (MPS) modified organic-inorganic hybrid silica monolithic column possessing vinyl ligands through thiol-ene click chemistry for capillary electrochromatography (CEC) is described. The proposed column is prepared via the sol-gel process by in situ co-condensation using vinyltrimethoxysilane (VTMS) and tetra-methoxysilane (TMOS) as precursors. Examination by SEM shows that the capillary has homogenous macroporous morphology and is well attached to the inner wall of the capillary. The obtained C(18)-MPS-VTMS silica hybrid monolithic column demonstrated an enhanced hydrophilic property and could be applied as a reversed-phase stationary phase in CEC directly. Compared with unmodified VTMS silica hybrid monolithic column, stronger EOF was observed using this monolithic column. VTMS/TOMS ratios in the reaction mixture were varied and 1:3 was found to be optimum. Good separations of benzenes, aromatic amines, acids and peptides were achieved, the lowest plate height of ≈ 3μm was obtained, the peak symmetry range from 0.98 to 1.29. The resulting C(18)-MPS-VTMS silica hybrid monolithic column can be used in different separation modes, including reversed phase mode and ion exchange mode.


Dental status of an institutionalized elderly population of 60 years and over in Qingdao, China.
The aim of this study was to investigate dental status of institutionalized elders and to relate outcomes with background variables and oral functionality. Dental status of 512 elders (≥60 years) from eight nursing homes in Qingdao were analyzed in terms of prevalence of decayed (D), missing (M), filled (F), and replaced teeth (R). Multivariate logistic regression was applied to determine relationships with the background variables age, gender, and SES. Prevalence of D, M, and F was analyzed also for separate dental regions. For determining oral functionality, prevalence of dentitions with ≥20 teeth without and with tooth replacements was plotted against age. Mean number of D varied from 3.8 at 60 years to 4.6 at 90 years, M from 3.6 at 60 years to 6.7 at 90 years for the lower jaw, and from 3.0 at 60 years to 8.0 at 90 years for the upper. Mean number of F in each jaw was low: 0.2 at 60 years to 0.4 at 90 years. Gender and SES effects were limited. Molars had significantly higher prevalence of D and M than premolar and anterior teeth. Seventy percent of participants of 60 years had ≥20 natural teeth and 12 % at 90 years. Including tooth replacements, 96 % at 60 years, and 84 % at 90 years had ≥20 teeth. In this sample of institutionalized elders, dental status of the majority of participants did not represent a functional dentition without tooth replacements. Institutionalized Chinese elders showed relatively low numbers of decayed teeth but high numbers of missing teeth.


Self-assessment scale for the community-based and emergency practice.
For current medical education, community-based primary care for the elderly is an essential topic. This study aimed to establish a scale of community-based assessment for clinical and emergency practice (C-CEP). A self-assessment scale for C-CEP was developed according to four steps. Initially, we reviewed publications from the societies of the United States, British, and Japan regarding educational goals. In addition, we searched MEDLINE for educational goals regarding attitude, skills, and knowledge. Getting together, we established 23 items as the educational goals of the C-CEP. Second, we collected responses for these 23 items from 5th-grade medical students (n = 195). Third, we conducted an exploratory factor analysis (EFA) using their responses to determine the fundamental structure of the self-assessment scale. Finally, a confirmatory factor analysis (CFA) was performed to assess the fitness of the self-assessment scale developing the EFA, resulting in modification of the items. In EFA and CFA results, C-CEP Scale consisted of four factors with 15 items: "Attitude and communication in emergency care," Basic clinical skills," "Knowledge of community healthcare," and "Knowledge of evidence-based medicine perseverance." The model fit indices were acceptable (Goodness of Fix Index = 0.928, Adjusted Goodness of Fit Index = 0.900, Comparative Fit Index = 0.979, and Root Mean Square Error of Approximation = 0.045). The values of McDonald's omega as an estimate of scale reliability were more than 0.7 in all four factors. As for test-retest reliability, the intraclass correlation coefficients were ≥ 0.58 for all factors. All four factors of the C-CEP Scale correlated positively with the Medical Professionalism Evaluation Scale subscales. We developed a valid and reliable self-assessment scale to assess student competence.


Assessment of the specificity of corvis biomechanical index-laser vision correction (CBI-LVC) in stable corneas after phototherapeutic keratectomy.
The Corvis Biomechanical Index-Laser Vision Correction (CBI-LVC) is a biomechanical index to detect ectasia in post-refractive surgery patients (PRK, LASIK, SMILE). This study aims to evaluate the distribution of the CBI-LVC in stable patients who underwent Phototherapeutic Keratectomy (PTK) compared to PRK patients. Patients who underwent PRK and PTK performed between 2000 and 2018 in Humanitas Research Hospital, Rozzano, Milan, Italy and remained stable for at least four years post-surgery were included. All eyes were examined with the Corvis ST (Oculus, Germany), whose output allows the calculation of the CBI-LVC. The distribution and specificity of the CBI-LVC in the two populations were estimated using a Wilcoxon Mann-Whitney test and compared. 175 eyes of 148 patients were included (85 eyes of 50 PTK patients and 90 eyes of 90 PRK patients). The distribution of CBI-LVC in the two groups showed a minor difference, with a median value in PRK patients of 0.000 (95% CI 0.000; 0.002) and 0.008 (95% CI 0.000; 0.037) in PTK patients (Mann-Whitney U test p = 0.023). The statistical analysis showed that the CBI-LVC provided a specificity of 92.22% in the PRK group, while in the PTK group it was 82.35%. Nevertheless, this difference was not statistically significant (Chi-squared test with Yates, p = 0.080). CBI-LVC provided similar specificity in stable PTK patients compared to those who underwent PRK. These results suggest that the CBI-LVC could be a useful tool to aid corneal surgeons in managing PTK patients.


Extending the quasi-steady state concept to analysis of metabolic networks.
A means is proposed for evaluating enzyme effectiveness in vivo via a simplified dynamic description of the metabolic reaction network within which the enzyme operates. The basis of the method is application of sensitivity analysis to a quasi-steady approximation of a complete dynamic model, and its implementation centers on interpreting the transient relations of selected intermediates following a perturbation to the system of interest: for many important situations such relations can be simply interpreted to give a useful global measure of enzyme effectiveness. This method is found to be successful for estimating phosphofructokinase and pyruvate kinase activity in the human red cell, and it appears promising as a basis for developing a means for detecting enzyme abnormalities caused by environmental or genetic factors. This method may also prove useful for comparative studies of glycolysis in different types of cells. The analysis presented is based on available models of red cell glycolysis, but the results are not highly sensitive to ambiguities in the system model. The approach suggested appears to provide an effective means for describing system dynamics and determining the behavior of an individual enzyme in an intact system by making a first-order allowance for interaction with the system as a whole. Requirements for success of this approach remain to be identified in detail, but effective time-scale separation is probably the key.


Green and facile synthesis of carboxymethylcellulose/ZnO nanocomposite hydrogels crosslinked with Zn2+ ions.
A green method was used for the preparation of functional carboxymethyl cellulose (CMC) hydrogel crosslinked by divalent zinc ions and incorporated with zinc oxide nanoparticles (ZnO) without using alkaline reagents. In the process, sodium carboxymethyl cellulose was used not only as a hydrogel matrix but also for the release of free hydroxyl groups, which increases the pH of the reaction mixture, consequently leading to the formation of ZnO. The chemical structure and morphology of the hydrogels were characterized using FTIR and FE-SEM analysis, respectively. The water absorption capacity of the hydrogels was studied as a function of temperature and pH. The results of FE-SEM showed the formation of ZnO particles in the hydrogel, while the water absorption capacity results supported the formation of zinc ion cross-linking within the carboxymethylcellulose chains. The CMC/ZnO nanocomposite hydrogel exhibited strong antimicrobial activity against pathogenic bacteria E. coli and L. monocytogenes.


Ecotoxicological evaluation of the antimalarial drug chloroquine.
There is limited information available about the potential environmental effects of chloroquine (CQ), a widely used antimalarial agent and a promising inexpensive drug in the management of HIV disease. The acute effects of CQ were studied using four ecotoxicological model systems. The most sensitive bioindicator was the immobilization of the cladoceran Daphnia magna, with an EC50 of 12 microM CQ at 72 h and a non-observed adverse effect level of 2.5 microM CQ, followed very closely by the decrease of the uptake of neutral red and the reduction of the lysosomal function in the fish cell line PLHC-1 derived from the top minnow Poeciliopsis lucida, probably due to the selective accumulation of the drug into the lysosomes. There was significant cellular stress as indicated by the increases on metallothionein and glucose-6P dehydrogenase levels after 24 h of exposure and succinate dehydrogenase activity mainly after 48 h. No changes were observed for ethoxyresorufin-O-deethylase (EROD) activity. The least sensitive model was the inhibition of bioluminescence in the bacterium Vibrio fischeri. An increase of more than five-fold in the toxicity from 24 to 72 h of exposure was observed for the inhibition of the growth in the alga Chlorella vulgaris and the content of total protein and MTS tetrazolium salt metabolization in PLHC-1 cells. At the morphological level, the most evident alterations in PLHC-1 cultures were hydropic degeneration from 25 microM CQ after 24h of exposure and the presence of many cells with pyknotic nuclei, condensed cytoplasm and apoptosis with concentrations higher than 50 microM CQ after 48 h of exposure. In conclusion, CQ should be classified as harmful to aquatic organisms.


Sleep deprivation and cellular responses to oxidative stress.
It has been hypothesized that sleep deprivation represents an oxidative challenge for the brain and that sleep may have a protective role against oxidative damage. This study was designed to test this hypothesis by measuring in rats the effects of sleep loss on markers of oxidative stress (oxidant production and antioxidant enzyme activities) as well as on markers of cellular oxidative damage (lipid peroxidation and protein oxidation). The analyses were performed in the brain and in peripheral tissues (liver and skeletal muscle), after short-term sleep deprivation (8 hours), after long-term sleep deprivation (3-14 days), and during recovery sleep after 1 week of sleep loss. Short-term sleep deprivation was performed by gentle handling; long-term sleep deprivation was performed using the disk-over-water method. Sleep research laboratory at University of Wisconsin-Madison. Adult male Wistar Kyoto rats (n = 69) implanted for polygraphic (electroencephalogram, electromyogram) recording. Aliquots of brain, liver, or skeletal muscle homogenate were used to assess oxidant production, superoxide dismutase activity, lipid peroxidation, and protein oxidation. No evidence of oxidative damage was observed at the lipid and/or at the protein level in long-term sleep-deprived animals relative to their yoked controls, nor in the cerebral cortex or in peripheral tissues. Also, no consistent change in antioxidant enzymatic activities was found after prolonged sleep deprivation, nor was any evidence of increased oxidant production in the brain or in peripheral tissues. The available data do not support the assumption that prolonged wakefulness may cause oxidative damage, nor that it can represent an oxidative stress for the brain or for peripheral tissue such as liver and skeletal muscle.


Cyclin D regulation of a sexually dimorphic asymmetric cell division.
The C. elegans somatic gonadal precursor cell (SGP) divides asymmetrically to establish gonad-specific coordinates in both sexes. In addition, the SGP division is sexually dimorphic and initiates sex-specific programs of gonadogenesis. Wnt/MAPK signaling determines the gonadal axes, and the FKH-6 transcription factor specifies the male mode of SGP division. In this paper, we demonstrate that C. elegans cyclin D controls POP-1/TCF asymmetry in the SGP daughters as well as fkh-6 and rnr expression in the SGPs. Although cyclin D mutants have delayed SGP divisions, the cyclin D defects are not mimicked by other methods of retarding the SGP division. We find that EFL-1/E2F has an antagonistic effect on fkh-6 expression and gonadogenesis, which is relieved by cyclin D activity. We propose that cyclin D and other canonical regulators of the G1/S transition coordinate key regulators of axis formation and sex determination with cell cycle progression to achieve the sexually dimorphic SGP asymmetric division.


Effects of hot-air microwave rolling blanching pretreatment on the drying of turmeric (Curcuma longa L.): Physiochemical properties and microstructure evaluation.
Blanching pretreatment can improve product quality and efficiency during food processing. Effects of hot-air microwave rolling blanching (HMRB) on physiochemical properties and microstructure of turmeric were investigated under various treatment times (0-10 min). Results showed that HMRB significantly changed weight, electrolyte leakage, texture, viscoelastic properties, pectin fractions content, thermal properties and drying quality of turmeric. Meanwhile, HMRB promoted the redistribution of water in turmeric and changed the cell structure, thus shortening drying time by 6.35-34.92 %. The polyphenol oxidase and peroxidase were entirely inactivated after blanching for 8 and 10 min, respectively. Compared with unblanched dried turmeric, the curcumin content, total phenolic, DPPH and ABTS were significantly increased by 20.76 %, 5.63 %, 7.54 % and 19.05 % at the optimal blanching time (8 min). Overall, HMRB can be used as a promising pretreatment technology to enhance the drying rate and improve the quality of dried turmeric.


A proposed scheme for the classification and surgical planning of falcine meningioma treatment.
Falcine meningiomas (FM) represent a surgical challenge even in the microsurgical era. An individualised surgical approach to different FM is indispensable, but there have been few reports in this regard. Thus, based on our series of 20 patients with FM who underwent surgery between October 2001 and June 2010, we propose a classification scheme for FM removal and demonstrate its effectiveness. FM in our series were classified into four types, according to tumour growth patterns on coronal MRI: Type I, hemispheroid-shaped tumours invaginating deeply into one hemisphere without shifting the falx (10 patients); Type II, olive-shaped tumours shifting the falx substantially to the contralateral side (six patients); Type IIIA, globular- or dumbbell-shaped tumours extending into both hemispheres, but to different extents (one patient); and Type IIIB, globular- or dumbbell-shaped tumours extending into both hemispheres to approximately equal extent (three patients). An ipsilateral interhemispheric approach was performed for Type I tumours, and a contralateral transfalcine approach for Type II. Type IIIA tumour was approached from the side where the smaller tumour was located. Type IIIB tumours were approached from the non-dominant hemisphere. Simpson grade I resection was achieved in all 20 patients. The follow-up ranged from 12 months to 114 months. There was no postoperative mortality, serious neurological deficits, or tumour recurrence. The preliminary results suggest that the proposed scheme can facilitate surgical planning and accomplish complete tumour resection with minimal invasion.


Chronic inflammatory disorders of the gastrointestinal tract of companion animals.
In the inflammatory bowel diseases (IBD) that affect dogs and cats there appears to be dysregulation of normal mucosal immunity, characterised by polyclonal lymphocytic infiltrates which are presumably specific for luminal antigens. There is an absence of a classical polarisation of either T-helper (Th) 1 or Th2 cytokine responses, although increased expression of mRNA for interleukin (IL) 2 and IL-12p40 and a shift towards mucosal immunoglobulin (Ig) G production are consistent findings, whilst variable responses are seen in tumour necrosis factor-alpha (TNF-alpha), IL-1, IL-4, IL-6, and interferon-gamma (IFN-gamma). Increased mucosal permeability and deranged intestinal motility are common sequelae. Despite obvious similarities with Crohn's disease and ulcerative colitis in humans, important differences exist. Of these, the diffuse superficial nature but with no Th1 or Th2 bias, and the prevalence of proximal small intestinal disease are notable. Potential hypotheses for these disparities include specific differences in the types or locations of agonistic gut flora, diffuse abnormalities in microbial-host interactions, a greater importance of diet, or anatomical or cellular differences in mucosal immune responses. Although specific pathogens and genetic susceptibilities may be involved, quantitative or qualitative changes in the normal flora or abnormal responses to a normal flora are more likely to be involved in the immunopathogenesis. Dietary influences include a large source of antigen, promotion of abnormal microbial growth through Maillard compounds within canned diets, and specific macro- and micronutrient deficiencies. Although dependent on a histopathological diagnosis, limitations of biopsies procured endoscopically, lack of histopathological standardisation and difficulty distinguishing inflammation from neoplasia remain significant problems. Clinician-pathologist dialogue, immunohistochemistry, cytokine profiling and lymphocyte clonality assessment may lead to more accurate diagnoses, a deeper understanding of the immunopathogenesis, and ultimately to new therapies or prevention of disease induction.


Mechanical determinants of myocardial energy turnover.
Energy turnover of the left ventricle does not differ in isovolumic contractions and contractions where pressure is released from peak to zero. This experimental result corresponds to predictions from a time varying elastance model of the mechanical and energetic properties of the left ventricle. To assess the validity of this model for cardiac muscle in general, experiments were designed to investigate whether mechanical and energetic behaviour of isolated cardiac muscle preparations could also be predicted from the time varying elastance model. The results obtained so far indicate, however, that not all experimental results can be accommodated by the model. This suggests that the value of the model may be limited.


Association between dust weather and number of admissions for patients with respiratory diseases in spring in Lanzhou.
Controlling the confounding factors on respiratory hospitalizations such as long-term trend, meteorological factor, atmospheric pollution, and calendar effect, the research is designed to study the effect of sand-dust weather on respiratory diseases from 2001 to 2005 in Lanzhou City on the basis of the semi-parametric generalized additive model (GAM). The results indicate that there is an association between sand-dust weather and the increase in respiratory hospitalizations, and with lagging effect. There are gender and age differences in the effect of sand-dust weather on health, on male severer than on female (RR value being 1.148 for male, while 1.144 for female without statistical significance), and much greater on the aged ≥ 65 years than on < 65 years (RR value being 1.266 for ≥ 65 yr, and 1.119 for < 65 yr).


Fine-scale population structure of blue whale wintering aggregations in the Gulf of California.
Population differentiation in environments without well-defined geographical barriers represents a challenge for wildlife management. Based on a comprehensive database of individual sighting records (1988-2009) of blue whales from the winter/calving Gulf of California, we assessed the fine-scale genetic and spatial structure of the population using individual-based approaches. Skin samples of 187 individuals were analyzed for nine microsatellite loci. A single population with no divergence among years and months and no isolation by distance (Rxy = 0.1-0.001, p>0.05) were found. We ran two bayesian clustering methods using Structure and Geneland softwares in two different ways: 1) a general analysis including all individuals in which a single cluster was identified with both softwares; 2) a specific analysis of females only in which two main clusters (Loreto Bay and northern areas, and San Jose-La Paz Bay area) were revealed by Geneland program. This study provides information indicating that blue whales wintering in the Gulf of California are part of a single population unit and showed a fine-scale structure among females, possibly associated with their high site fidelity, particularly when attending calves. It is likely that the loss of genetic variation is minimized by male mediated gene flow, which may reduce the genetic drift effect. Opportunities for kin selection may also influence calf survival and, in consequence, have a positive impact on population demography in this small and endangered population.


Bronchial responsiveness to methacholine is increased in citrus red mite (Panonychus citri)-sensitive children without asthmatic symptoms.
A recent investigation has suggested that citrus red mite (Panonychus citri, CRM) is a common sensitizing allergen among children living around citrus farms. A cross-sectional survey was performed to evaluate the bronchial responsiveness to methacholine in CRM-sensitive children without asthmatic symptoms. A total of 375 children living around citrus farms were enrolled in this study. There were 201 boys and 174 girls with a mean age of 12.5 (range 7-16) years. Each subject was evaluated by a questionnaire, a skin prick test with 13 common inhalant allergens including CRM, and a methacholine bronchial provocation test (MBPT). Positive rate of MBPT (PC20-methacholine < 25 mg/mL) was higher in atopic rhinitic and atopic control children than in nonatopic rhinitic and nonatopic control subjects (41.3% and 33.3% vs 17.2% and 15.4%, respectively, both P < 0.05). Slope of dose-response curve (DRS, %/mg/mL) was higher in atopic rhinitic children than in nonatopic rhinitic, atopic control and nonatopic control subjects (14.3 +/- 0.87 vs 9.4 +/- 0.72, 10.0 +/- 1.37 and 9.2 +/- 1.51, P < 0.05, respectively). Both the positive rate of MBPT and the DRS were increased in children with positive skin response to CRM than in those without sensitization (48.2% vs 22.9%, P = 0.0001; 15.6 +/- 1.26 vs 10.2 +/- 0.65, P = 0.0001). Bronchial responsiveness is increased in citrus red mite-sensitive children even if they have no asthmatic symptoms.


Simplifying the evaluation of primary health care programmes.
Currently, there is considerable attention for health impact--as measured by mortality, morbidity or nutrition indicators, in the evaluation of primary health care (PHC) programmes. In most cases, health impact evaluations tend to be dominated by methodological discussions on data collection, analysis and interpretation, which are not relevant to the majority of PHC programmes. In this paper a theoretical framework of variables, affecting child survival, is presented. The key to this action-oriented framework is the identification of a set of intermediate variables which directly affect the health status of children, but can be influenced by PHC interventions as well. It is recommended that evaluations of PHC programmes should focus on these intermediate variables and be less concerned with health impact of the interventions.


Molecular dynamics of mismatch detection-How MutS uses indirect readout to find errors in DNA.
The mismatch repair protein MutS safeguards genomic integrity by finding and initiating repair of basepairing errors in DNA. Single-molecule studies show MutS diffusing on DNA, presumably scanning for mispaired/unpaired bases, and crystal structures show a characteristic "mismatch-recognition" complex with DNA enclosed within MutS and kinked at the site of error. But how MutS goes from scanning thousands of Watson-Crick basepairs to recognizing rare mismatches remains unanswered, largely because atomic-resolution data on the search process are lacking. Here, 10 μs all-atom molecular dynamics simulations of Thermus aquaticus MutS bound to homoduplex DNA and T-bulge DNA illuminate the structural dynamics underlying the search mechanism. MutS-DNA interactions constitute a multistep mechanism to check DNA over two helical turns for its 1) shape, through contacts with the sugar-phosphate backbone, 2) conformational flexibility, through bending/unbending engineered by large-scale motions of the clamp domain, and 3) local deformability, through basepair destabilizing contacts. Thus, MutS can localize a potential target by indirect readout due to lower energetic costs of bending mismatched DNA and identify a site that distorts easily due to weaker base stacking and pairing as a mismatch. The MutS signature Phe-X-Glu motif can then lock in the mismatch-recognition complex to initiate repair.


Distinct patterns of short-chain fatty acids during flare in patients with ulcerative colitis under treatment with mesalamine or a herbal combination of myrrh, chamomile flowers, and coffee charcoal: secondary analysis of a randomized controlled trial.
Short-chain fatty acids are involved in the regulation of the gut immune system. In ulcerative colitis, short-chain fatty acids are often reduced, especially during flare. This study evaluated exploratively the pattern of butyrate and total short-chain fatty acids in patients with ulcerative colitis during flare treated either with mesalamine or a herbal preparation consisting of myrrh, chamomile flowers, and coffee charcoal which showed promising results in maintaining remission in a randomized double-blind, double-dummy, controlled clinical trial (EudraCT-Number 2007-007928-18). Patients were treated with the herbal preparation or mesalamine. Clinical activity was monitored by Clinical Colitis Activity Index. Using gas chromatography, we analyzed fecal samples of 38 patients who experienced a flare during treatment. Paired t-test showed a significant decline of total short-chain fatty acids [M before = 66.12, SD = 39.59; M after = 29.83, SD = 15.05; 95% bootstrap confidence interval (20.53-55.30); P = 0.01) and of butyrate [M before 11.35, SD = 7.56; M after = 6.50, SD = 3.55; 95% bootstrap confidence interval (2.06-8.11); P = 0.02] in the event of a flare for patients treated with mesalamine but not for patients treated with the herbal preparation. Patients who received the herbal preparation did not show a significant decline of total short-chain fatty acids in the event of a flare. Since a decline of short-chain fatty acids might lead to unfavorable health impairments, a combination of the two treatments should be further investigated.


Effect of glucose deprivation of GLUT 1 expression in 3T3-L1 adipocytes.
Elevated glucose transport rates during glucose deprivation are phenomena that have been observed in several different types of cells in culture. We show here that glucose transport rates in 3T3-L1 adipocytes increased by 10-fold within 18 h in response to glucose deprivation, confirming earlier work by Van Putten and Krans (Van Putten, J. P. M., and Krans, H. M. J. (1985) J. Biol. Chem. 260, 7996-8001). Mannose and 3-O-methylglucose (a nonmetabolizable glucose analog), but not fructose or galactose, blocked the increase in transport activity. Although the increase in transport was dependent on new protein synthesis, only a small and transient increase in GLUT 1 mRNA (less than 2-fold) was observed. In addition, the level of the normal isoform of GLUT 1 (46 kDa) did not increase. A lower molecular mass isoform (37 kDa) was observed but not until 15 h after glucose removal, the appearance of which was clearly not correlated with the increase in activity. Further, the extracellular glucose concentration required to elicit accumulation of this form (p37) was 2 orders of magnitude less than that required for transport stimulation (5 microM versus 500 microM glucose; p37 accumulation and transport activation, respectively). Interestingly, p37 was seen in the presence of galactose, but not fructose, despite elevated transport activity with either sugar. The p37 isoform was slightly larger than N-glycosidase F-treated GLUT 1 (36 kDa), implying that this form is still glycosylated, albeit incompletely. It is not known if p37 is functional, but the time- and sugar-dependent appearance of the lower isoform suggests that p37 is not responsible for starvation-induced transport but potentially represents an underglycosylated precursor of the normal, 46-kDa isoform of GLUT 1.


You-gui Pill ameliorates renal tubulointerstitial fibrosis via inhibition of TGF-β/Smad signaling pathway.
You-gui Pill (YGP), a traditional Chinese medicinal prescription, was widely used to warm and recuperate "kidney-yang" clinically for hundreds of years in China. Recent studies found that YGP had a potential benefit for renoprotection. The present study aimed to elucidate the in vivo and in vitro efficacy of YGP on renal tubulointerstitial fibrosis, and the molecular mechanism is also investigated. Rat renal tubulointerstitial fibrosis model was elicited by unilateral ureteral obstruction (UUO). Sprague-Dawley rats underwent UUO and were studied after 14 days. Animals were randomly subjected to six groups: sham, UUO, UUO/YGP (0.14, 0.42, 1.26g/kg/d), and UUO/enalapril (10mg/kg/d). HE, Masson and ELISA were used for evaluate renal injury and function. Immunohistochemical analysis and western blot were used to detect the expressions of α-SMA, fibronectin, collagen matrix and Smads. In vitro studies were investigated in TGF-β1-stiumlated NRK-49F cell line. Oral administration of YGP significantly decreased UUO-induced inflammatory cell infiltration, tubular atrophy and interstitial fibrosis, and there was no significant difference between YGP at 1.26g/kg and enalapril at 10mg/kg treatment (P>0.05). Meanwhile, serum creatinine and blood urea nitrogen levels were reduced dramatically (P<0.01). In coincide with the decreased of TGF-β1, α-SMA, fibronectin and collagen matrix expressions were also declined with YGP treatment in both UUO kidneys and TGF-β1-stimulated NRK-49F cell line. Additionally, nuclear translocation of p-Smad2/3 was markedly down-regulated by YGP (P<0.001), with a relative mild up-regulated expression of Smad7 (P<0.05). Our findings demonstrate that YGP had a renoprotective effect in ameliorating renal tubulointerstitial fibrosis, and this activity possibly via suppression of the TGF-β and its downstream regulatory signaling pathway, including Smad2/3.


Challenges and coping strategies among distance education learners: Implication for human resources managers.
This study examined challenges and coping strategies among distance education learners and their implications for human resources managers. The quantitative and descriptive survey design was adopted, and a sample of 1358 university students pursuing distance programmes was drawn from a study population of 44,458 distance undergraduate and postgraduate students. The data collection instrument was a questionnaire, and the data obtained was analysed with Partial Least Square Structural Equation Modelling (PLS-SEM). The study found that instructional challenges, psychlogical challenges, socio-religious challenges and institutional challenges had a statistically significant relationship with coping strategies and educational output among distance learners. Coping strategies also obtained a statistically significant relationship with educational output. The four main effective coping strategies identified among distance learners were problem-focused, emotion-focused, preventive and proactive coping strategies. It was recommended that human resource managers provide orientation, counselling on coping strategies, decent and suitable teaching and learning facilities, supply modules and communicate assessment feedback on time, and provide competent and committed course tutors to help reduce challenges faced by distance learners.


Prehospital use of heparin locks: a cost-effective method for intravenous access.
Intravenous (IV) infusions were ordered in nearly 95% of paramedic runs called into a busy base station hospital. Most of the patients received IV lines for either prophylactic access or administration of single or multiple bolus medications. In this group of patients, the application of a heparin lock injection port directly to the IV catheter, followed by the injection of 10 units of heparin, was evaluated. Of 102 consecutive patients treated in the field, 98 (97%) were treated with heparin locks only. The total number of patients requiring an IV infusion drip (either by paramedics or in the emergency department of the receiving hospital) was 20 (20%). If all 102 patients had received conventional IV drip infusions, the total patient equipment charges would have been $4,610.40. The actual charges for all patients in this series, either with heparin locks or IV infusion sets, was $1,846.14--a 60% savings. The results of the study indicate that the heparin lock is a safe, convenient, and cost-effective method for maintaining IV access in the prehospital environment.


Change in social status and risk of low birth weight in Denmark: population based cohort study.
To estimate the risk of having a low birthweight infant associated with changes in social, environmental, and genetic factors. Population based, historical cohort study using the Danish medical birth registry and Statistic Denmark's fertility database. All women who had a low birthweight infant (< 2500 g) (index birth) and a subsequent liveborn infant (outcome birth) in Denmark between 1980 and 1992 (exposed cohort, n = 11,069) and a random sample of the population who gave birth to an infant weighing > or = 2500 g and to a subsequent liveborn infant (unexposed cohort, n = 10,211). Risk of having a low birthweight infant in the outcome birth as a function of changes in male partner, area of residence, type of job, and social status between the two births. Women in the exposed cohort showed a high risk (18.5%) of having a subsequent low birthweight infant while women in the unexposed cohort had a risk of 2.8%. After adjustment for initial social status, a decline in social status increased the absolute risk of having a low birthweight infant by about 5% in both cohorts, though this was significant only in the unexposed cohort. Change of male partner did not modify the risk of low birth weight in either cohort. Having had a low birthweight infant and a decline in social status are strong risk factors for having a low birthweight infant subsequently.


Preparation and characterization of chitosan-carbon nanotube scaffolds for bone tissue engineering.
In recent years, significant development has been given to chitosan for orthopedic application. In this study, we have prepared scaffolds with the use of low and high molecular weight chitosan with 0.0025%, 0.005% and 0.01% weight of f-multiwalled carbon nanotube (f-MWCNT) by freezing and lyophilization method and physiochemically characterized as bone graft substitutes. Fourier Transform Infrared Spectroscopy, X-Ray Diffraction Analysis, Thermal Gravimetric Analysis, Scanning Electron Microscopy and Optical Microscopy results indicated that the f-MWCNT was uniformly dispersed in chitosan matrix and there was a chemical interaction between chitosan and f-MWCNT. The water uptake ability and porosity of scaffolds increased with an increase the amount of f-MWCNT. The cell proliferation, protein content, alkaline phosphatase and mineralization of the composite scaffolds were higher than chitosan scaffold due to the addition of f-MWCNT. Herewith, we are suggesting that chitosan/f-MWCNT scaffolds are promising biomaterials for bone tissue engineering.


Metalorganic chemical vapor deposition growth of InAs/GaSb type II superlattices with controllable AsxSb1-x interfaces.
InAs/GaSb type II superlattices were grown on (100) GaSb substrates by metalorganic chemical vapor deposition (MOCVD). A plane of mixed As and Sb atoms connecting the InAs and GaSb layers was introduced to compensate the tensile strain created by the InAs layer in the SL. Characterizations of the samples by atomic force microscopy and high-resolution X-ray diffraction demonstrate flat surface morphology and good crystalline quality. The lattice mismatch of approximately 0.18% between the SL and GaSb substrate is small compared to the MOCVD-grown supperlattice samples reported to date in the literature. Considerable optical absorption in 2- to 8-μm infrared region has been realized.PACS: 78.67.Pt; 81.15.Gh; 63.22.Np; 81.05.Ea.


A rapid, sensitive method for the simultaneous quantitation of estradiol and estradiol conjugates in a variety of tissues: assay development and evaluation of the distribution of a brain-enhanced estradiol-chemical delivery system.
A rapid and sensitive method that permits the simultaneous quantitation of estradiol (E2) and the E2 conjugate [estradiol 17-(1,4-dihydrotrigonellinate)] in biological tissues from rats is described. This method development was necessitated by the design of this E2-chemical delivery system (E2-CDS) which permits the predictable metabolism of the E2-CDS to a charged quaternary ion (E2-Q+) and its subsequent hydrolysis to slowly liberate E2. Based upon in vitro determinations of the rates of oxidation of E2-CDS to E2-Q+ and hydrolysis of E2-Q+ to E2, we anticipated that concentrations of E2-Q+ would be several orders of magnitude higher in tissues than E2. Three steps were used to extract and prepare samples for the radioimmunoassay (RIA) of estradiol. The first step is homogenization and extraction of the biological samples with an organic solvent; the second step is the base catalyzed hydrolysis of the E2 conjugate in 1 N NaOH; and the third step utilizes solid-phase extraction (SPE) with C18 reversed-phase columns which provide a means of achieving a rapid and precise extraction and separation of E2. The analysis of plasma samples does not require the initial solvent extraction. All purified E2 samples were then reconstituted in the assay buffer and assayed by RIA for E2. The application of this procedure to the determination of E2-Q+ and E2 in biological materials was assessed for specificity, reliability and recovery in vitro by using tissues and plasma from rats and in vivo evaluations of the distribution of E2 and E2-Q+ were done using rats treated with 1 mg E2-CDS/kg. Our in vitro analyses revealed that E2 and E2-Q+ could be differentially extracted with a high recovery and that both compounds could be specifically and reliably assayed in brain, plasma, anterior pituitary, liver, kidney, lung, heart and adipose tissue. In vivo analyses revealed that following a single i.v. injection of E2-CDS, brain levels of E2 exceeded serum levels by 30-, 41-, and 82-fold while brain levels of E2-Q+ exceeded serum levels by 33-, 70-, and 294-fold at 1, 7 and 14 days, respectively. Collectively, these data indicate that E2-Q+ and E2 can be reliably quantitated in a variety of tissues following the administration of an E2-chemical delivery system.


Spontaneous orbital polarization in the nematic phase of FeSe.
The origin of nematicity in FeSe remains a critical outstanding question towards understanding unconventional superconductivity in proximity to nematic order. To understand what drives the nematicity, it is essential to determine which electronic degree of freedom admits a spontaneous order parameter independent from the structural distortion. Here we use X-ray linear dichroism at the Fe K pre-edge to measure the anisotropy of the 3d orbital occupation as a function of in situ applied stress and temperature across the nematic transition. Along with using X-ray diffraction to precisely quantify the strain state, we reveal a lattice-independent, spontaneously ordered orbital polarization within the nematic phase, as well as an orbital polarizability that diverges as the transition is approached from above. These results provide strong evidence that spontaneous orbital polarization serves as the primary order parameter of the nematic phase.


Impact of esophageal temperature monitoring guided atrial fibrillation ablation on preventing asymptomatic excessive transmural injury.
Even with the use of a reduced energy setting (20-25 W), excessive transmural injury (ETI) following catheter ablation of atrial fibrillation (AF) is reported to develop in 10% of patients. However, the incidence of ETI depends on the pulmonary vein isolation (PVI) method and its esophageal temperature monitor setting. Data comparing the incidence of ETI following AF ablation with and without esophageal temperature monitoring (ETM) are still lacking. This study was comprised of 160 patients with AF (54% paroxysmal, mean: 24.0±2.9 kg/m(2)). Eighty patients underwent ablation accompanied by ETM. The primary endpoint was defined as the occurrence of ETI assessed by endoscopy within 5 d after the AF ablation. The secondary endpoint was defined as AF recurrence after a single procedure. If the esophageal temperature probe registered >39 °C, the radiofrequency (RF) application was stopped immediately. RF applications could be performed in a point-by-point manner for a maximum of 20 s and 20 W. ETI was defined as any injury that resulted from AF ablation, including esophageal injury or periesophageal nerve injury (peri-ENI). The incidence of esophageal injury was significantly lower in patients whose AF ablation included ETM compared with patients without ETM (0 [0%] vs. 6 [7.5%], p=0.028), but not the incidence of peri-ENI (2 [2.5%] vs. 3 [3.8%], p=1.0). AF recurrence 12 months after the procedure was similar between the groups (20 [25%] in the ETM group vs. 19 [24%] in the non-ETM group, p=1.00). Catheter ablation using ETM may reduce the incidence of esophageal injury without increasing the incidence of AF recurrence but not the incidence of peri-ENI.


Spatial and temporal expression of the Grainyhead-like transcription factor family during murine development.
The Drosophila transcription factor Grainyhead (grh) is expressed in ectoderm-derived tissues where it regulates several key developmental events including cuticle formation, tracheal elongation and dorsal closure. Our laboratory has recently identified three novel mammalian homologues of the grh gene, Grainyhead-like 1, -2 and -3 (Grhl1-3) that rewrite the phylogeny of this family. Using gene targeting in mice, we have shown that Grhl3 is essential for neural tube closure, skin barrier formation and wound healing. Despite their extensive sequence homology, Grhl1 and Grhl2 are unable to compensate for loss of Grhl3 in these developmental processes. To explore this lack of redundancy, and to gain further insights into the functions of this gene family in mammalian development we have performed an extensive in situ hybridisation analysis. We demonstrate that, although all three Grhl genes are highly expressed in the developing epidermis, they display subtle differences in the timing and level of expression. Surprisingly, we also demonstrate differential expression patterns in non-ectoderm-derived tissues, including the heart, the lung, and the metanephric kidney. These findings expand our understanding of the unique role of Grhl3 in neurulation and epidermal morphogenesis, and provide a focus for further functional analysis of the Grhl genes during mouse embryogenesis.


The homeopathic approach to the treatment of symptoms of oestrogen withdrawal in breast cancer patients. A prospective observational study.
This paper reports on an investigation of the homeopathic approach to the management of symptoms of oestrogen withdrawal in women with breast cancer. Forty-five patients entered the study. The most common presenting symptoms were hot flushes (HF) (n=38), mood disturbance (n=23), joint pain (n=12), and fatigue (n=16). Other symptoms included sleeplessness, reduced libido, weight gain, cystitis, vaginal dryness and skin eruptions. The active intervention was an individualised homeopathic medicine. Forty women (89%) completed the study. Significant improvements in mean symptom scores were seen over the study period and for the primary end-point 'the effect on daily living' scores. Symptoms other than HF such as fatigue and mood disturbance appear to be helped. Significant improvements in anxiety, depression and quality of life were demonstrated over the study period. The homeopathic approach appears to be clinically useful in the management of oestrogen withdrawal symptoms in women with breast cancer whether on or off Tamoxifen and improves mood disturbance. A placebo-controlled trial would be the next stage in this line of inquiry.


Comparison of three different C18 HPLC columns with different particle sizes for the optimization of aflatoxins analysis.
In this work we compared the performance of chromatography columns with particles of 5 and 3 μm with the new 2.7 μm solid core particles for the analysis of aflatoxins B1, G1, B2, and G2 using trifluoroacetic acid pre-column derivatization. Three different columns have been used and chromatographic parameters as retention time, resolution, limit of detection (LOD), limit of quantification (LOQ) were obtained from all of them and compared. The results show that comparing with the traditional columns, shorter columns (100 mm × 4.6 mm) with the new solid core particles are suitable for the analysis of these mycotoxins and allowed the reduction of the analysis time by 45.5% and 33.3% with respect to columns with particle size 5 μm (150 mm × 4.6 mm) and 3 μm (150 mm × 4.6 mm) respectively, without any detrimental effect on performance. This leads to the reduction of the analysis costs by saving on organic solvents and increasing the total number of analyses per day. The capability of these columns for analyzing samples, in different culture media, was assessed by analyzing different samples from: yeasts extract sucrose medium, corn meal agar medium and fresh hazelnut media.


Development and validation of a simple screening tool for caregiver grief in dementia caregiving.
Loss and grief are experienced by caregivers of persons with dementia (PWD), relating to the ambiguous loss of PWD even when they are still alive and the anticipation of future loss related to their physical death. Such experience of caregiver grief is not easily recognized in clinical practice, despite its association with adverse effects such as caregiver burden, caregiver depression and caregivers' desire to place the PWD in nursing homes. We constructed a simple screening tool - based on factors associated with caregiver grief - to identify caregivers with high grief. Spouses or children of community-dwelling PWD (n = 403) completed self-administered questionnaires containing a well-established grief scale and information related to the caregiver and PWD. We split the study sample into two - the derivation sample (n = 300) was used to identify factors associated with grief (using logistic regression) and derive a simple tool based on the number of identified factors; the validation sample (n = 103) evaluated the performance of the tool using the receiver-operating-characteristic-curve-analysis (ROC). Four key factors were identified by the multivariable regression - more severe dementia (odds ratio, OR 6.9), behavioral problems in PWD (OR 5.0), spousal caregivers (OR 6.0) and daily caregiving (OR 3.0). The screening tool (based on the number of key factors) had an area under ROC of 0.77. At the optimal cut-off of ≥2 key factors, the tool had a sensitivity of 0.91 and a specificity of 0.42. The identified factors are consistent with current understanding on caregiver grief. They can be easily integrated into the workflow of routine services to screen for caregivers who are more likely to benefit from further grief-related assessment.


Binding and detoxification of heavy metals in lower vertebrates with reference to metallothionein.
1. The metabolism of Cu, Zn, Cd and Hg in lower vertebrates is described, using fish as a model. 2. The main part of this review deals with metallothionein and the role of this protein for the storage and detoxification of these metals. 3. Factors influencing the bioavailability and probable uptake routes are identified. 4. The distribution of the metals within the organism is outlined. The distribution between tissues is described and the subcellular distribution discussed with reference to metallothionein.


Ggamma -37 (A-->T): a new nondeletional hereditary persistence of fetal hemoglobin determinant associated with the rare codon 91 (+T) delta0-thalassemia.
We recently described a rare frameshift mutation in the delta-globin gene in a Dutch patient, in association with a new mutation of the Ggamma-globin gene promoter [Ggamma -37 (A-->T)] with a moderately elevated Hb F level of 2.3%. The delta mutation at codon 91 (+T) has been described once before in our laboratory in 1989, in a complex Belgian family with Ggamma (Agammadeltabeta)0-thalassemia (thal) and moderately elevated Hb F levels, without the Ggamma (Agammadeltabeta)0-thal deletion in some individuals. Analysis of the patients from 1989 revealed the presence of the same Ggamma-globin gene mutation and moderately elevated Hb F in all patients, who were also carriers of the delta-globin gene frameshift. Further analysis demonstrated that the two mutations were in linkage with the same haplotype in both the Belgian family and the recently found patient, confirming the association of the elevated Hb F expression with the new Ggamma-globin gene mutation.


Genome-wide survey of transcriptional initiation in the pathogenic fungus, Candida glabrata.
DNA sequencing of the 5'-flanking region of the transcriptome effectively identifies transcription initiation sites and also aids in identifying unknown genes. This study describes a comprehensive polling of transcription start sites and an analysis of full-length complementary DNAs derived from the genome of the pathogenic fungus Candida glabrata. A comparison of the sequence reads derived from a cDNA library prepared from cells grown under different culture conditions against the reference genomic sequence of the Candida Genome Database (CGD: http://www.candidagenome.org/) revealed the expression of 4316 genes and their acknowledged transcription start sites (TSSs). In addition this analysis also predicted 59 new genes including 22 that showed no homology to the genome of Saccharomyces cerevisiae, a genetically close relative of C. glabrata. Furthermore, comparison of the 5'-untranslated regions (5'-UTRs) and core promoters of C. glabrata to those of S. cerevisiae showed various global similarities and differences among orthologous genes. Thus, the C. glabrata transcriptome can complement the annotation of the genome database and should provide new insights into the organization, regulation, and function of genes of this important human pathogen.


The project implicit international dataset: Measuring implicit and explicit social group attitudes and stereotypes across 34 countries (2009-2019).
For decades, researchers across the social sciences have sought to document and explain the worldwide variation in social group attitudes (evaluative representations, e.g., young-good/old-bad) and stereotypes (attribute representations, e.g., male-science/female-arts). Indeed, uncovering such country-level variation can provide key insights into questions ranging from how attitudes and stereotypes are clustered across places to why places vary in attitudes and stereotypes (including ecological and social correlates). Here, we introduce the Project Implicit:International (PI:International) dataset that has the potential to propel such research by offering the first cross-country dataset of both implicit (indirectly measured) and explicit (directly measured) attitudes and stereotypes across multiple topics and years. PI:International comprises 2.3 million tests for seven topics (race, sexual orientation, age, body weight, nationality, and skin-tone attitudes, as well as men/women-science/arts stereotypes) using both indirect (Implicit Association Test; IAT) and direct (self-report) measures collected continuously from 2009 to 2019 from 34 countries in each country's native language(s). We show that the IAT data from PI:International have adequate internal consistency (split-half reliability), convergent validity (implicit-explicit correlations), and known groups validity. Given such reliability and validity, we summarize basic descriptive statistics on the overall strength and variability of implicit and explicit attitudes and stereotypes around the world. The PI:International dataset, including both summary data and trial-level data from the IAT, is provided openly to facilitate wide access and novel discoveries on the global nature of implicit and explicit attitudes and stereotypes.


The effect of education on the incidence of dementia and Alzheimer's disease in the Framingham Study.
To evaluate whether low educational attainment is a risk factor for the incidence of dementia and Alzheimer's disease (AD) in the Framingham Study and to determine whether age at onset of dementia is earlier in persons with low educational levels. A community-based cohort was studied longitudinally for the development of dementia. Diagnosis was made according to strict criteria by two neurologists and a neuropsychologist. Subtype of dementia and year at onset were determined. Incidence rates were compared in three education groups: < grade school, < high school, and > or = high school. A total of 3,330 men and women aged 55 to 88 years. During 17 years of follow-up, 258 incident cases of dementia, including 149 AD cases, were identified. Unadjusted incidence rates were significantly elevated (p < 0.05) for dementia and non-AD dementia among the least educated. The age-adjusted relative risk for subjects with a grade school education or less compared with those who earned a high school diploma was 1.31 (95% confidence interval [CI], 0.90 to 1.90) for dementia generally, 1.04 (95% CI, 0.62 to 1.74) for AD, and 1.75 (95% CI, 1.03 to 2.98) for non-AD dementia. Age at onset of dementia did not vary by educational attainment. After age adjustment, low educational attainment was not a significant risk factor for the incidence of dementia generally or of AD. Low educational attainment was associated with increased risk of non-AD dementia, perhaps because of deleterious smoking habits and other risk factors for stroke in the least-educated individuals. Adequately adjusting for age and examining subtypes of dementia are important in assessing the influence of education on dementia incidence.


Pd nanoparticles synthesized in situ with the use of Euphorbia granulate leaf extract: Catalytic properties of the resulting particles.
For the first time the extract of the plant of Euphorbia granulate was used to green synthesis of Pd nanoparticles (NPs) as a heterogeneous catalyst for the phosphine-free Suzuki-Miyaura coupling reaction at room temperature. This method is a facile and eco-friendly way in organic synthesis using the plant extract as biomedia, bioreductant and capping ligand which considerably stabilizes the surface of Pd NPs. The presence of flavonoid and phenolics acids in the extract could be responsible for the reduction of Pd(2+) ions and formation of the corresponding Pd NPs.


Transnational Mobility and Utilization of Health Services in Northern Thailand: Implications and Challenges for Border Public Health Facilities.
Transnational populations from the Association of Southeast Asian Nations are crossing borders regardless of whether their status is legal or undocumented, to receive health services in the border regions of Thailand. The implications and challenges of transnational mobility and the utilization of public health facilities in Thailand's border regions are therefore investigated in this study. Four public health facilities were selected, located in 2 economically-active border areas in Northern Thailand: Mae Sai-Tachileik at the Thailand-Myanmar border and Chiang Saen-Ton Phueng at the Thailand-Lao PDR border. Qualitative data were obtained from in-depth interviews with 8 medical and non-medical hospital staff responsible for implementing facility-level policies and providing health services for the transnational population. Five themes were identified through analysis of the implications and challenges for transnational mobility and the utilization of public health facilities under study: contextual determinants of illness in specific border areas; uncompensated care as opposed to financial management in serving the transnational population; health service opportunities for the transnational population; cross-border collaboration on public health; and the remaining challenges of transnational mobility in border regions. Conventional content analysis with interpretative induction of in-depth interview data offers recommendations for improving the capacity of border health facilities to reduce the burden placed upon them to provide services to the transnational population.


[Construction of enterohemorrhagic Escherichia coli O157:H7 strains with espF gene deletion and complementation].
To construct enterohemorrhagic Escherichia coli (EHEC) O157:H7 strains with delection espF gene and its nucleotide fragment and with espF gene complementation. A pair of homologous arm primers was designed to amplify the gene fragment of kanamycin resistance, which was transformed into EHEC O157:H7 EDL933w strain via the PKD46 plasmid by electroporation. The replacement of the espF gene by kanamycin resistance gene through the PKD46-mediated red recombination system was confirmed by PCR and sequencing. The entire coding region of espF along with its nucleotide fragment was amplified by PCR and cloned into pBAD33 plasmid, which was transformed into a mutant strain to construct the strain with espF complementation. RT-PCR was used to verify the transcription of espF and its nucleotide fragment in the complemented mutant strain. We established EHEC O157:H7 EDL933w strains with espF gene deletion and with espF gene complementation. Both espF and its nucleotide fragment were transcribed in the complemented mutant strain. The two strains provide a basis for further study of the regulatory mechanism of espF.


Effect of surgical approach on risk of recurrence after vaginal brachytherapy in early-stage high-intermediate risk endometrial cancer.
The objective was to determine if surgical approach affects time to recurrence in early-stage high-intermediate risk endometrial cancer (HIR-EC) treated with adjuvant vaginal brachytherapy (VBT). In this retrospective cohort study, HIR-EC patients treated with VBT between 2005 and 2017 were identified and those who received open or minimally invasive hysterectomies (MIS) were included. Clinical and surgical variables were analyzed and time to recurrence was compared between surgical groups. We identified 494 patients, of which 363 had MIS hysterectomies, 92.5% had endometrioid histology, 45.7% were stage IA and 48.0% stage IB. Open hysterectomy patients had higher BMIs (p = 0.007), lower rates of lymph node sampling (p < 0.001) and lymphovascular space invasion (LVSI) (p = 0.036), however in patients who recurred, no differences were noted between groups. Overall, 65 patients (13.2%) recurred, 14 in the open group (10.7%) and 51 in the MIS group (14.0%) (p = 0.58), while vaginal recurrences were noted in 4.6% and 6.1% respectively. When compared to the open group, the MIS group had a significantly shorter time to any recurrence (p = 0.022), to pelvic (p = 0.05) and locoregional recurrence (p = 0.021) and to death from any cause (p = 0.039). After adjusting for age, BMI, grade, LVSI and surgery date, the MIS group had a higher risk of any recurrence (HR 2.29 (1.07-4.92), p = 0.034) and locoregional recurrence (HR 4.18 (1.44-12.1), p = 0.008). Patients with HIR-EC treated with VBT after MIS hysterectomy have a shorter time to recurrence and higher risk of recurrence when compared to open hysterectomy patients. Further studies into the safety of MIS in high-intermediate risk patients are required.


Realist synthesis protocol for understanding which strategies are effective to prevent urinary tract infection in older people in care homes.
To identify and characterize strategies, which contribute to the prevention of urinary tract infection (UTI) in older people living in care homes. The realist synthesis has four iterative stages to (1) develop initial programme theory; (2) search for evidence; (3) test and refine theory supported by relevant evidence and (4) formulate recommendations. Data from research articles and other sources will be used to explore the connection between interventions and the context in which they are applied in order to understand the mechanisms, which influence the outcomes to prevent UTI. A scoping search of the literature and workshops with stakeholders will identify initial programme theories. These theories will be tested and refined through a systematic search for evidence relating to mechanisms that trigger prevention and recognition of UTI in older people in care homes. Interviews with key stakeholders will establish practical relevance of the theories and their potential for implementation. UTI is the most commonly diagnosed infection in care home residents. Evidence on the effectiveness of strategies to prevent UTI in long-term care facilities does not address the practicality of implementing these approaches in UK care homes. The realist synthesis is designed to examine this important gap in evidence. Our evidence-informed programme theory will help inform programmes to improve practice to reduce the incidence of UTI in older people living in care homes and related research. Patient and public involvement will be crucial to ensuring that our findings reach carers and the public. Involvement of patient and public representatives is embedded throughout the study to ensure it is underpinned by multiple perspectives of importance to care home residents. Our co-investigator representing patient and public involvement is a lay member of the team and will chair the Project Advisory Group, which has two additional lay members. This will help to ensure that our findings and resources reach carers and the public and represent their voice in our publications and presentations to professional and lay audiences.


IL-17/IL-17 Receptor Pathway-Mediated Inflammatory Response in Apostichopus japonicus Supports the Conserved Functions of Cytokines in Invertebrates.
Inflammation participates in host defenses against infectious agents and contributes to the pathophysiology of many diseases. IL-17 is a well-known proinflammatory cytokine that contributes to various aspects of inflammation in vertebrates. However, the functional role of invertebrate IL-17 in inflammatory regulation is not well understood. In this study, we first established an inflammatory model in the Vibrio splendidus-challenged sea cucumber Apostichopus japonicus (Echinodermata). Typical inflammatory symptoms, such as increased coelomocyte infiltration, tissue vacuoles, and tissue fractures, were observed in the V. splendidus-infected and diseased tissue of the body wall. Interestingly, A. japonicus IL-17 (AjIL-17) expression in the body wall and coelomocytes was positively correlated with the development of inflammation. The administration of purified recombinant AjIL-17 protein also directly promoted inflammation in A. japonicus Through genome searches and ZDOCK prediction, a novel IL-17R counterpart containing FNIII and hypothetical TIR domains was identified in the sea cucumber genome. Coimmunoprecipitation, far-Western blotting, and laser confocal microscopy confirmed that AjIL-17R could bind AjIL-17. A subsequent cross-linking assay revealed that the AjIL-17 dimer mediates the inflammatory response by the specific binding of dimeric AjIL-17R upon pathogen infection. Moreover, silencing AjIL-17R significantly attenuated the LPS- or exogenous AjIL-17-mediated inflammatory response. Functional analysis revealed that AjIL-17/AjIL-17R modulated inflammatory responses by promoting A. japonicus TRAF6 ubiquitination and p65 nuclear translocation and evenly mediated coelomocyte proliferation and migration. Taken together, our results provide functional evidence that IL-17 is a conserved cytokine in invertebrates and vertebrates associated with inflammatory regulation via the IL-17-IL-17R-TRAF6 axis.


Quality of Life with the Rehabilitation After Partial Mandibulectomy: a Systematic Review.
To evaluate the QoL before and after prosthetic rehabilitation of partial mandibulectomy patients based on the type of surgery, effects of radiation, the type of prosthesis, and to enlist their outcome on the rehabilitation. Literature search as per PICO format was carried out within a time range from January 2000 to June 2021. The review followed PRISMA guidelines and registered with the PROSPERO(CRD42021258472). The focus question was established as per the PICO format (Population, Intervention, Comparison, Outcome). The population involved partial mandibulectomy individuals with prosthetic rehabilitation as an intervention. The outcome, quality of life (QoL), was compared with the pre and post partial mandibulectomy patients rehabilitated with a prosthesis. The search yielded 367 articles and based on the search criteria only 7 articles were suitable for qualitative analysis. Marginal resection of the mandible is less aggressive than segmental resection which provided function, phonation, and esthetics at acceptable levels but the food mixing ability was reduced when resection is accompanied by glossectomy. However, the perceived chewing ability and OHRQoL were not accountable to the extent of surgical excision. An overall increase in the QoL on rehabilitation with acrylic prosthesis depicting satisfactory functionality with a considerable improvement in mastication, speech, and social life. QoL and Denture Satisfaction Index did not differ based on the number of implants in an implant overdenture prosthesis, but the chewing ability was improved. An increase in the number of remaining occlusal units improved the overall QoL. Restoration of the function, psychological comfort, and improvement in esthetics was significant in patients who underwent prosthetic rehabilitation. The QoL between conventional and implant prostheses was observed to be more similar, and the effect of remaining hard and soft tissue structures has a major influence on patient comfort signifying the influence of the extent of surgical excision. The online version contains supplementary material available at 10.1007/s13193-022-01664-x.


The ulnar-mammary syndrome gene, Tbx3, is a direct target of the retinoic acid signaling pathway, which regulates its expression during mouse limb development.
TBX3, a member of the T-box transcription factor gene family, is a transcriptional repressor that is required for the development of the heart, limbs, and mammary glands. Mutations in TBX3 that result in reduced functional protein lead to ulnar-mammary syndrome, a developmental disorder characterized by limb, mammary gland, tooth, and genital abnormalities. Increased levels of TBX3 have been shown to contribute to the oncogenic process, and TBX3 is overexpressed in several cancers, including breast cancer, liver cancer, and melanoma. Despite its important role in development and postnatal life, little is known about the signaling pathways that modulate TBX3 expression. Here we show, using in vitro and in vivo assays, that retinoic acid (RA) activates endogenous TBX3 expression, which is mediated by an RA-receptor complex directly binding and activating the TBX3 promoter, and we provide evidence that this regulation may be functionally relevant in mouse embryonic limb development. Our data identify TBX3 as a direct target of the RA signaling pathway and extend our understanding of the role and regulation of TBX3 in limb development.


A new chromatin flavor to cap chromosomes: Where structure, function, and evolution meet.
Soman, A., Wong, S.Y., et al. find that telomeric DNA assembles into a new high-order chromatin structure resembling a columnar stack of nucleosomes with dynamic properties. This raises new questions on telomere biology mechanisms and chromatin evolution.


Odorant stimulation of secretory and neural processes in the salamander olfactory mucosa.
Topical application of the odorants guaiacol (10(-3) mol/l, 1-30 min) and 2-isobutyl-3-methoxypyrazine (IBMP, 10(-5)-10(-3) mol/l, 15 min) caused time- and concentration-dependent reductions in the secretory granule content of acinar cells of the superficial Bowman's glands (sBG) and moderate to extensive vacuolation in acinar cells of sBG and deep olfactory glands (dG). Topical application of 9.8 mg/ml scopolamine 10 min before 10(-4) mol/l IBMP significantly reduced the amount of secretory granule depletion from sBG compared to that seen with IBMP alone and resulted in less extensive vacuolation in sBG and dG acinar cells. The i.p. injection of 42 mg/kg propranolol 10 min before topical application of 10(-4) mol/l IBMP had no effect on the action of IBMP. Guaiacol and IBMP also had time- and concentration-dependent effects on the secretory activity of sustentacular cells in the olfactory epithelium. The protrusion of secretory material into the mucociliary matrix that covers the epithelial surface and vacuolation within the secretory material resulted from odorant application. Scopolamine and propranolol had no effects on the action of IBMP on sustentacular cell secretory activity. When applied in the vapor phase, guaiacol elicited action potentials recorded from individual olfactory receptor neurons; the impulse frequency was concentration-dependent and showed tonic and phasic components when the duration of stimulation was varied. Low to moderate concentrations of IBMP delivered in the vapor phase evoked monophasic negative slow voltage transients recorded from the surface of the olfactory mucosa. The amplitudes of these transients increased with increasing stimulus concentrations. Higher concentrations or longer stimulus durations evoked longer-latency positive-voltage generating processes and negative afterpotentials. The properties of the electrophysiological responses to both odorants were characteristic of responses evoked by a wide variety of 'typical' odorants.


KCa1.1 K+ Channel Inhibition Overcomes Resistance to Antiandrogens and Doxorubicin in a Human Prostate Cancer LNCaP Spheroid Model.
Several types of K+ channels play crucial roles in tumorigenicity, stemness, invasiveness, and drug resistance in cancer. Spheroid formation of human prostate cancer (PC) LNCaP cells with ultra-low attachment surface cultureware induced the up-regulation of cancer stem cell markers, such as NANOG, and decreased the protein degradation of the Ca2+-activated K+ channel KCa1.1 by down-regulating the E3 ubiquitin ligase, FBXW7, compared with LNCaP monolayers. Accordingly, KCa1.1 activator-induced hyperpolarizing responses were larger in isolated cells from LNCaP spheroids. The pharmacological inhibition of KCa1.1 overcame the resistance of LNCaP spheroids to antiandrogens and doxorubicin (DOX). The protein expression of androgen receptors (AR) was significantly decreased by LNCaP spheroid formation and reversed by KCa1.1 inhibition. The pharmacological and genetic inhibition of MDM2, which may be related to AR protein degradation in PC stem cells, revealed that MDM2 was responsible for the acquisition of antiandrogen resistance in LNCaP spheroids, which was overcome by KCa1.1 inhibition. Furthermore, a member of the multidrug resistance-associated protein subfamily of ABC transporters, MRP5 was responsible for the acquisition of DOX resistance in LNCaP spheroids, which was also overcome by KCa1.1 inhibition. Collectively, the present results suggest the potential of KCa1.1 in LNCaP spheroids, which mimic PC stem cells, as a therapeutic target for overcoming antiandrogen- and DOX-resistance in PC cells.


Identification of multiple in vivo phosphorylation sites in rabbit myelin basic protein.
Myelin basic protein of rabbit brain (Mr = 18,200) was initially freed of the bulk of the nonphosphorylated species (mainly component 1) by Cm-cellulose chromatography at high pH. The remainder of the protein was subjected to peptic digestion at pH 6.00, which resulted in specific, essentially complete cleavage at several bonds (Phe-44--Phe-45, Phe-87--Phe-88, Leu-109--Ser-110, and Leu-151--Phe-152) and partial cleavage at the Tyr-14--Leu-15 bond. Gel filtration of the digest through Sephadex G-25 (fine) yielded three fractions, the first containing primarily peptides 1-44 and 45-87, the second peptides 15-44, 88-109, and 110-151, and the third peptides 1-14 and 152-168. Each fraction was chromatographed on Cm-cellulose at pH 8.2, and the resulting subfractions and partially purified peptides were analyzed for phosphoserine and phosphothreonine. Materials containing significant amounts of the phosphoamino acids were subsequently chromatographed on Cm-cellulose at pH 4.65, and the analyses for phosphoserine and phosphothreonine were repeated. The resulting purified peptic phosphopeptides were identified by amino acid analysis and tryptic peptide mapping. Comparison of the maps with those of the unphosphorylated counterparts located the tryptic phosphopeptides. These were recovered and their identities were established by amino acid analysis. In those cases where the phosphopeptide contained 2 Ser residues, the position of the phosphoserine was established by aminopeptidase M digestion. Five phosphorylation sites were found: Ser-7, Ser-56, Thr-96, Ser-113, and Ser-163. Only a small fraction of these sites was phosphorylated in the total basic protein, with values ranging from about 2 (ser-113) to 6% (Thr-96). With the possible exception of Ser-56, these sites are not the ones that have been reported to be phosphorylated in vitro by cyclic AMP-dependent protein kinase.


Treatment of anemia in patients with HIV Infection--Part 2: guidelines for management of anemia.
The key treatment goal for managing anemia in patients infected with HIV is to maintain an improved or normal hemoglobin level. Whenever possible, the identification and treatment of the underlying cause of anemia is the primary therapeutic strategy. After excluding other etiologies, the Nursing Guidelines Committee for Anemia in Patients With HIV Infection has recommended that patients with mild asymptomatic anemia (hemoglobin level = 1 g/dl below the lower limit of the normal range) receive nutritional support and more frequent screening. Recombinant human erythropoietin (epoetin alfa) therapy is an appropriate treatment option for patients with symptomatic mild anemia or moderate anemia (hemoglobin level = 2 g/dl below the lower limit of the normal range). An immediate blood transfusion may be required under specific instances for patients with severe anemia (hemoglobin level less than or equal to 8 g/dl).


Binding of 18-carbon unsaturated fatty acids to bovine β-lactoglobulin--structural and thermodynamic studies.
Binding of 18-carbon unsaturated oleic and linoleic acid to lactoglobulin, the milk protein, has been studied for the first time by isothermal titration calorimetry (ITC) and X-ray crystallography. Crystal structures determined to resolution 2.10 Å have revealed presence of single fatty acid molecule bound in β-barrel, the primary binding site, with carboxyl group hydrogen bonded to Glu62. The aliphatic chain of both ligands is in almost linear conformation and their interactions with the protein are similar to observed in structure of lactoglobulin with stearic acid. The ITC experiments showed that binding of unsaturated fatty acids to LGB is spontaneous and exothermic. The stoichiometry of binding is lower than 1.0, association constant is 9.7 × 10(5)M(-1) and 9.0 × 10(5)M(-1) for oleic and linoleic acid, respectively. Solvent relief seems to be the major contributor to entropic changes upon fatty acid binding to lactoglobulin.


Explant culture of adult goldfish retina: a model for the study of CNS regeneration.
Conditions are described for culture of retinal explants of adult goldfish which favour outgrowth of neuritic processes onto a substratum. A growth index to quantitate the outgrowth was developed. If the optic nerve is crushed several days prior to explantation, a marked enhancement of neuritic outgrowth is seen relative to control retinas. Histological examination of the explants revealed that retinal ganglion cells in explants from unoperated eyes became hypertrophied in vitro with a time course similar to that observed in vivo following optic nerve crush. Experiments with hemiaxotomized retinas indicate that the perikaryal regenerative response is mediated intracellularly.