High prevalence of obesity-related hypertension among adults aged 40 to 79 years in Southwest China.
This study aimed to assess the prevalence and related factors of obesity-related hypertension among adults aged 40 to 79 years in Southwest China. From September 2013 to March 2014, a multi-stage, stratified sampling method was conducted on 10,589 people aged 40 to 79 years and living in Chengdu and Chongqing investigated by using a questionnaire and performing physical and biochemical measurements. The prevalence of obesity-related hypertension and hypertension overall (systolic ≥130 mmHg and/or diastolic ≥80 mmHg or treated hypertension) was 22.8% and 57.4%, respectively, among all participants. For obesity-related hypertension, the prevalence was higher in women than in men (24.7% versus 19.4%, p < 0.001). For people in the age ranges of 40-49, 50-59, 60-69, and ≥70, the prevalence of obesity-related hypertension were 11.8%, 22.6%, 30.7%, and 36.6%, respectively. Participants with obesity-related hypertension as opposed to those with non-obesity-related hypertension had a higher prevalence of hypertriglyceridemia, high low-density lipoprotein cholesterolemia, diabetes, and hyperuricemia (all p < 0.05). Multivariate logistic regression analysis showed that age, female gender, current smoking, hypertriglyceridemia, diabetes and family history of hypertension were all positively correlated with obesity-related hypertension, whereas higher education level and having spouse were negatively correlated with obesity-related hypertension. The prevalence of obesity-related hypertension was high among adults aged 40 to 79 years in Southwest China. Cardiometabolic abnormalities among participants with obesity-related hypertension were more serious and frequently present than in those with non-obesity-related hypertension. Aggressive and holistic strategies aiming at the prevention and treatment of obesity-related hypertension are needed.


Automated determination of phenolic compounds in wine, berry, and grape samples using 96-blade solid phase microextraction system coupled with liquid chromatography-tandem mass spectrometry.
An automated 96-thin-film solid phase microextraction system was optimized for high throughput analysis of phenolic compounds in wine, berry, and grape samples. Liquid chromatography and tandem mass spectrometry methods were optimized and applied for separation and detection of compounds. Evaluation of five different stationary phases showed that polystyrene-divinylbenzene-polyacrylonitrile (PS-DVB-PAN) is the optimum extraction phase for the extraction of phenolic compounds under study. The thin-film PS-DVB-PAN SPME coating provided almost exhaustive extraction recovery for all phenolics compounds under study, except for naringenin with 80% recovery. Extraction efficiency, inter- and intra-day reproducibility, sensitivity, linearity, limit of detection and quantitation, and matrix effect were evaluated. Intra-day and inter-day reproducibility were in the respective range of 4-8 and 7-13% relative standard deviation (RSD) for all eight phenolic compounds. Limits of detection and quantitation of the proposed SPME-LC-MS/MS system for the analysis of analytes under study were found in the range of 0.2-3 and 0.5-10 ng/mL, respectively. Standard addition calibration was applied for the quantitative determination of unknown phenolic compounds from wine, berry, and grape samples. The assessment of matrix effect showed significant reduction of ion suppression/enhancement using SPME method in comparison with that of solvent extraction technique.


A developmental role for catecholamines in Drosophila behavior.
Tyrosine hydroxylase (TH), the enzyme which catalyzes the conversion of tyrosine to L-DOPA and is the rate limiting step in catecholamine biosynthesis, is genetically expressed during development in Drosophila. Null mutant alleles of the single copy gene which codes for this enzyme are developmentally lethal as is a conditional TH mutant at its restrictive temperature. In adult flies, inhibition of TH by alpha-methyl-p-tyrosine (alphaMT) decreases locomotor activity in a dose-dependent manner. This behavioral effect is accompanied by reductions in brain levels of dopamine, the primary CNS catecholamine in Drosophila, and can be prevented by the coadministration of L-DOPA. Similar effects are found with reserpine and at the restrictive temperature in flies with a temperature conditional mutation for TH. In agreement with published studies in mammals, inhibition of TH by alphaMT during Drosophila development results in enhanced expression of this enzyme in the progeny of surviving adults. This biochemical outcome is accompanied behaviorally by increased sensitivity to the locomotor effects of both alphaMT and reserpine, drugs which act via depletion of brain catecholamines. Since TH is the rate limiting enzyme responsible for the conversion of tyrosine to L-DOPA and L-DOPA is converted to dopamine by aromatic amino acid decarboxylase (AAAD), the results indicate that depletion of catecholamine levels in the fly embryo results in increased dopamine biosynthesis in the next generation accompanied by alterations in behavior.


Stable expression of immunoglobulin gene V(D)J recombinase activity by gene transfer into 3T3 fibroblasts.
Using retroviral recombination substrates, we investigated the developmental stage of expression of V(D)J recombinase activity and the activation of recombinase activity in nonlymphoid cells. V(D)J recombinase activity was detected only in pre-B cells, but a DNA transfer protocol successfully activated V(D)J recombination in an NIH 3T3 cell line. The V(D)J recombinase activity was transferred in a second round of transfection and was then stably expressed in fibroblasts at a level comparable to that of a recombinationally active pre-B cell. It is likely that expression of a single, lymphoid-specific gene in a fibroblast is sufficient to confer V(D)J recombinase activity on that cell.


[Mutant thiopurine S-methyltransferase alleles among Jing Chinese in Guangxi province].
To investigate the mutant alleles of thiopurine S-methyltransferase (TPMT) among Jing Chinese. Polymerse chain reaction-single strand conformation polymorphism (PCR-SSCP) techniques were developed for assaying exons 5, 7 and 10 of the TPMT gene respectively and were used to detect mutant TPMT alleles among Jing Chinese. Two cases of TPMT*3C (A719G) heterozygotes were identified in 103 Jing Chinese; other deleterious alleles such as TPMT*2 (G238C), TPMT*3A (G460A/A719G) and TPMT*3B (G460A) were not found; 27 cases of silent mutant allele TPMT*1S (T474C) were also identified (5 homozygotes and 22 heterozygotes). The PCR-SSCP assay established and adopted in this study was sensitive and reliable, which could be used to detect mutant TPMT alleles. Allele frequency of TPMT*3C is low among Jing Chinese (1.0%), and TPMT*3C appears to be the most prevalent deleterious allele in this population.


Higher incidence of diffuse Pigmented Villonodular Synovitis in patients with ruptured cruciate ligament: A case report.
Pigmented Villonodular Synovitis (PVNS) is a kind of extremely rare and not easily diagnosed disease, while the occurrence following the anterior cruciate ligament (ACL) rupture is comparably high. Here we reported 2 patients presenting knee swelling, pain, and giving away symptoms following a rupture of ACL history. Clinical and radiological findings were supportive of ACL rupture and PVNS, prompting the patient to undergo surgery. The synovium was completely removed with the help of an arthroscope. Reconstruction of the ruptured ACL was carried out a few months later. At the last follow-up visit, both the patients were doing well with no recurrence of pain, swelling, or give way sensation. The diagnosis of PVNS is often difficult because in the early stages, symptoms are often non-specific and pathological examination remains the gold standard for the diagnosis of PVNS. We have reviewed some of the previously reported literature on PVNS, suggesting that joint instability may be an important risk factor for PVNS and summarizing the treatment options for PVNS. More attention should be paid to the incidence of PVNS in patients with joint instability, particularly in patients with cruciate ligament injuries. Early and reliable stabilization of the joint may significantly prevent PVNS and ensure a better clinical outcome.


Recovery versus persistence of disordered mineral metabolism in kidney transplant recipients.
In patients with end-stage renal disease, successful renal transplantation improves the quality of life and increases survival, as compared with long-term dialysis treatment. Although it long has been believed that successful kidney transplantation to a large extent solves the problem of chronic kidney disease-mineral and bone disorders (CKD-MBD), increasing evidence indicates that it only changes the phenotype of CKD-MBD. Posttransplant CKD-MBD reflects the effects of immunosuppression, previous CKD-MBD persisting after transplantation, and de novo CKD-MBD. A major and often-underestimated problem after successful renal transplantation is persistent hyperparathyroidism. Besides contributing to posttransplant hypercalcemia and hypophosphatemia, persistent hyperparathyroidism may be involved in the pathogenesis of allograft dysfunction (nephrocalcinosis), progression of vascular calcification, and bone disease (uncoupling of bone formation and bone resorption and bone mineral density loss) in renal transplant recipients. Similar to nontransplanted patients, CKD-MBD has a detrimental impact on (cardiovascular) mortality and morbidity. Additional studies urgently are needed to get more insights into the pathophysiology of posttransplant CKD-MBD. These new insights will allow for a more targeted and causal therapeutic approach.


Transcriptome sequencing reveals improved ammonia nitrogen tolerance in Zebra II strain of the Manila clam Ruditapes philippinarum.
In this research, we identified genes associated with ammonia nitrogen (TAN) stress response and resistance in juveniles of the Zebra II strain and a wild population of the Manila clam Ruditapes philippinarum. Both groups were subjected to a 96 h acute toxicity test using TAN concentrations of 17.617 ± 0.634 and 16.670 ± 0.7 mg/l, respectively. We then collected samples, conducted transcriptome sequencing and screened the sequences for differentially expressed genes (DEGs) related to TAN stress response. We identified 2908 and 2861 DEGs in the Zebra II and wild clam groups, respectively, and the two groups had 626 DEGs in common. The verified DEGs had less of a detoxification effect in the wild population than that in the Zebra II group. Gene Ontology database analysis showed that Zebra II juveniles were mainly enriched in protein phosphorylation, purine nucleoside binding, and kinase activity, whereas the wild population juveniles were primarily enriched in oxidases activity, organic acid metabolic processes, and extracellular regions. Kyoto Encyclopedia of Genes and Genomes pathway analysis mainly highlighted aminoacyl tRNA biosynthesis in Zebra II juveniles and sphingolipid metabolism, FOXO signaling, biosynthesis of aminoacyl tRNA, and other pathways in the wild population. These results show that the toxic effect of TAN on the Manila clam is related to a variety of pathways, which are mainly related to immune response, inflammatory response, metabolic pathways, and nerve conduction. This study provides basic data and theoretical reference for revealing the molecular regulation mechanism of the improved TAN tolerance of Zebra II strain as compared with the wild population of Ruditapes philippinarum.


Expression of threonine synthase from Solanum tuberosum L. is not metabolically regulated by photosynthesis-related signals or by nitrogenous compounds.
Although the control of carbon fixation and nitrogen assimilation has been studied in detail, little is known about the regulation of carbon and nitrogen flow into amino acids. In this paper the isolation of a cDNA encoding threonine synthase is reported (TS; EC 18.104.22.168) from a leaf lambda ZAP II-library of Solanum tuberosum L. and the transcriptional regulation of the respective gene expression in response to metabolic changes. The pattern of expression of TS by feeding experiments of detached petioles revealed that TS expression is regulated neither by photosynthesis-related metabolites nor by nitrogenous compounds. The present study suggests that the regulation of the conversion of aspartate to threonine is not controlled at the transcript level of TS. The nucleotide and deduced amino acid sequences of potato TS show homology to other known sequences from Arabidopsis thaliana and microorganisms. TS is present as a low copy gene in the genome of potato as demonstrated in Southern blot analysis. When cloned into a bacterial expression vector, the cDNA did functionally complement the Escherichia coli mutant strain Gif41. TS transcript was found in all tissues of potato and was most abundant in flowers and source leaves.


Electrical stimulation for stress incontinence.
Electrical stimulation has been reported to be effective for stress incontinence, cure and improvement rates being reported to range from 30% to 50%, and from 6% to 90%, respectively. However, clinical application of this treatment is not common because there is little physiological and technical information. Electrodes for electrical stimulation are divided into two types: external (non-implantable) and internal (implantable), and there are two methods of stimulation: chronic (long-term, continuous) and short-term. Frequencies of 20-50 Hz, with a pulse duration of 1-5 ms, have been reported to be effective for urethral closure. The effectiveness of the treatment should be verified with placebo-controlled double-blinded trials, and four such studies using an active and a sham device have been reported. Two of these verified the superiority of the active device over the sham device, but the others did not demonstrate any significant difference between the two with regard to efficacy. Electrical stimulation has been reported to result in a long-term continuation of therapeutic effect. The effect has been explained as a re-education or a reactivation of lost functions of the pelvic floor muscles. As to adverse effects, there may be some complications in relation to anesthesia or surgical procedures, such as infection, pain and bleeding with implantable electrodes. The incidence of adverse effects in short-term electrical stimulation is less than 14%. In conclusion, short-term electrical stimulation using non-implantable anal or vaginal electrodes is the most recommendable because of safety and ease of use.


State-dependent cross-inhibition between transmitter-gated cation channels.
Transmitter-gated cation channels are detectors of excitatory chemical signals at synapses in the nervous system. Here we show that structurally distinct alpha3beta4 nicotinic and P2X2 channels influence each other when co-activated. The activation of one channel type affects distinct kinetic and conductance states of the other, and co-activation results in non-additive responses owing to inhibition of both channel types. State-dependent inhibition of nicotinic channels is revealed most clearly with mutant P2X2 channels, and inhibition is decreased at lower densities of channel expression. In synaptically coupled myenteric neurons, nicotinic fast excitatory postsynaptic currents are occluded during activation of endogenously co-expressed P2X channels. Our data provide a molecular basis and a synaptic context for cross-inhibition between transmitter-gated channels.


Total hip replacement with dorsal acetabular rim augmentation using the SOP(TM) implant and polymethylmethacrylate cement in seven dogs with dorsal acetabular rim deficiency.
To describe a surgical technique for reinforced augmentation of the dorsal acetabular rim (DAR) using a string-of-pearls (SOP™) locking plate and polymethylmethacrylate (PMMA) bone cement, and to report clinical outcome in 7 dogs. Case series. Dogs (n=7). Medical records (November 2009-April 2010) of 7 dogs with large DAR deficits, that had total hip replacement (THR) with reinforced augmentation of the DAR using a SOP™ plate and PMMA were evaluated retrospectively. Reinforced augmentation of the DAR involved anchorage of a precontoured 2.0 or 2.7 mm SOP™ plate dorsal to the acetabulum followed by application of PMMA cement to cover the reamed acetabulum and plate. Cemented acetabular components were used. Implant associated complications were recorded and ≥6-month follow-up obtained. In all dogs, lameness improved at medium-term reassessment (median, 8 months; range, 6-11 months). Complications included transient sciatic neurapraxia in 2 dogs, which resolved by 3 months. Reinforced augmentation of the DAR using a SOP™ plate and PMMA cement may facilitate placement of acetabular THR component implantation in dogs with severe DAR insufficiency.


Bacteria-propelled microtubular motors for efficient penetration and targeting delivery of thrombolytic agents.
Effective thrombolysis is critical to rapidly rebuild blood flow for thrombosis patients. Drug delivery systems have been developed to address inadequate pharmacokinetics of thrombolytic agents, but challenges still remain in the timely removal of blood clots regarding the dense fibrin networks. Herein, rod-shaped tubular micromotors were developed to achieve efficient penetration and thorough destruction of thrombi. By using electrospun fiber fragments as the template, urokinase (uPA)-loaded polydopamine (PDA) microtubes with surface decorated fucoidan (FuPDAuPA) were prepared at the aspect ratio of around 2. One E. coli Nissle 1917 (EcN) was assembled into one microtube to construct a FuPDAuPA@EcN hybrid micromotor through PDA adhesion and L-aspartate induction. The pharmacokinetic analysis indicates that the encapsulation of uPA into micromotors extends the half-life from 0.4 to 5.6 h and increases the bioavailability over 10 times. EcN-propelled motion elevates adsorption capacities of FuPDAuPA@EcN for more than four times compared with that of FuPDAuPA. The fucoidan-mediated targeting causes 2-fold higher thrombolysis capacity in vitro and over 10-fold higher uPA accumulation in thrombi in vivo. In the treatment of venous thrombi at mouse hindlimbs, intravenous administration of FuPDAuPA@EcN completely removed blood clots with almost full recovery of blood flows and apparently alleviated tail bleeding. It should be noted that FuPDAuPA@EcN treatment at a reduced uPA dose caused no significant difference in the blood flow rate compared with those of FuPDAuPA. The synergistic action of fucoidan-induced targeting and EcN-driven motion provides a prerequisite for promoting thrombolytic efficacy and reducing uPA dose and bleeding side effect. STATEMENT OF SIGNIFICANCE: The standard treatment to thrombosis patient is intravenous infusion of thrombolytic agents, but the associated bleeding complications and impairment of normal haemostasis greatly offset the therapeutic benefits. Drug delivery systems have been developed to address the limitations of inadequate pharmacokinetics of thrombolytic agents, but challenges still exist in less efficient penetration into dense networks for thorough destruction of thrombi. Up to now only few attempts have been made to construct nano-/micromotors for combating thrombosis and there is no single case that antithrombosis is assisted by bacteria or cells-propelled motors. Herein, bacteria-propelled microtubes were developed to carry urokinase for efficient penetration into blood clots and effective thrombolysis. The synergistic action of bacteria-driven motion and specific ligand-induced targeting holds a promising treatment strategy for life-threatening cardiovascular diseases such as thrombosis and atherosclerosis.


Protecting Free-Living Dormice: Molecular Identification of Cestode Parasites in Captive Dormice (Muscardinus avellanarius) Destined for Reintroduction.
The success of any population translocation programme relies heavily on the measures implemented to control and monitor the spread of disease. Without these measures, programmes run the risk of releasing immunologically naïve species or, more dangerously, introducing novel infectious agents to native populations. As a precaution, a reintroduction programme for the common or hazel dormouse, Muscardinus avellanarius, in England screens dormice before release following captive breeding. Using PCR sequencing of a range of genes, we tested whether the same species of tapeworm(s) were present in captive and free-living dormice. Whilst only Rodentolepis straminea were identified in free-living dormice, cestode ova found in a captive individual produced a molecular match closely related to Hymenolepis microstoma and a previously unrecorded Rodentolepis species. To prevent putting at risk the free-living population, we recommended the continued treatment of dormice showing tapeworm infection before release. Our work demonstrates how molecular techniques can be used to inform reintroduction programmes, reduce risk from disease and increase chances of reintroduction success.


Preventive effects of genistein on motor dysfunction following 6-hydroxydopamine injection in ovariectomized rats.
Estrogen and phytoestrogens such as the isoflavones have received considerable attention in Parkinson's disease (PD) research. Because they have been reported to possess neuroprotective effects on dopaminergic neurons in the substantia nigra (SN), isoflavones appear particularly promising for post-menopausal women at risk for PD. However, most previous studies were limited to morphological investigation, and the preventive effects of isoflavones on motor function have not been evaluated. The aim of the present study was to elucidate the prevention by an isoflavone against motor dysfunction after injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle of ovariectomized rats, which mimics post-menopausal status in women. Pretreatment with genistein, an isoflavone, significantly preserved motor function in rats injected with low-dose 6-OHDA, as evaluated by the stepping and cylinder tests. An estrogen receptor antagonist, ICI182780, reversed the effects of genistein, indicating that this effect of genistein is mediated through estrogen receptors. The functional effects of genistein were accompanied by preservation of tyrosine hydroxylase-immunoreactive neurons in the SN after injection of low-dose 6-OHDA. These findings suggest that genistein may be useful for the prevention of PD in post-menopausal women.


Atomic- and Molecular-Level Design of Functional Metal-Organic Frameworks (MOFs) and Derivatives for Energy and Environmental Applications.
Continuing population growth and accelerated fossil-fuel consumption with recent technological advancements have engendered energy and environmental concerns, urging researchers to develop advanced functional materials to overcome the associated problems. Metal-organic frameworks (MOFs) have emerged as frontier materials due to their unique porous organic-inorganic hybrid periodic assembly and exceptional diversity in structural properties and chemical functionalities. In particular, the modular nature and modularity-dependent activity of MOFs and MOF derivatives have accentuated the delicate atomic- and molecular design and synthesis of MOFs, and their meticulous conversion into carbons and transition-metal-based materials. Synthetic control over framework architecture, content, and reactivity has led to unprecedented merits relevant to various energy and environmental applications. Herein, an overview of the atomic- and molecular-design strategies of MOFs to realize application-targeted properties is provided. Recent progress on the development of MOFs and MOF derivatives based on these strategies, along with their performance, is summarized with a special emphasis on design-structure and functionality-activity relationships. Next, the respective energy- and environmental-related applications of catalysis and energy storage, as well as gas storage-separation and water harvesting with close association to the energy-water-environment nexus are highlighted. Last, perspectives on current challenges and recommendations for further development of MOF-based materials are also discussed.


Comorbid Insomnia and Sleep Apnea: Assessment and Management Approaches.
Comorbid insomnia and sleep apnea (COMISA) is a highly prevalent and debilitating condition that is more difficult to treat compared with insomnia alone or sleep apnea alone. Approximately 30% to 50% of sleep clinic patients with sleep apnea report comorbid insomnia symptoms. Comorbid insomnia is associated with lower adherence to positive airway pressure therapy for obstructive sleep apnea. Management approaches that include targeted treatments for both insomnia and sleep apnea lead to the best treatment outcomes for patients with COMISA. Therefore, sleep clinics should incorporate insomnia and COMISA management pathways including access to cognitive behavioral therapy for insomnia.


Ectopic lingual thyroid tissue and acquired hypothyroidism: case report.
Ectopic thyroid tissue with thyroid gland in its normal location is an extremely rare phenomenon. We present a case of a 38-year-old woman who was referred to our hospital with symptoms of hypothyroidism. Thyroid hormone measurement revealed clinical hypothyroidism with elevated anti-thyroid antibodies, neck ultrasonography showed a small tissue with the characteristic of Hashimoto thyroiditis, while the scintigraphy demonstrated only a lingual thyroid. Treatment consisted in L-thyroxine replacement to the euthyroid state. We reviewed the literature with respect to the embryological background and the clinical management of such cases.


Medium- and long-term survival after pacemaker implant: Improved survival with right ventricular outflow tract pacing.
Long-term prognosis after pacemaker implant depends on numerous variables, particularly structural heart disease. There is evidence that apical stimulation could favor the development of heart failure and, therefore, influence mortality. Other right ventricular pacing sites have been studied, for example the outflow tract, but no reports regarding long-term clinical outcome are available. Compare all-cause mortality between two different sites of stimulation in the right ventricle. We retrospectively analyzed 150 consecutive patients who underwent pacemaker implantation because of complete AV block (spontaneous or after AV node ablation), symptomatic second-degree AV block, and symptomatic atrial fibrillation with slow ventricular response. All patients were implanted at the same institution with the standard technique. Apical stimulation was performed with a passive or active fixation lead and outflow tract pacing with an active fixation lead. Data collection period began in July 1999 and ended on December 2004. All patients included were greater than 70% ventricular paced during pacemaker follow-up. Patients older than 85 years were excluded from the analysis. Age, pacemaker mode, sex, ejection fraction, diabetes, and structural cardiac disease were analyzed. Mean age was 72+/-7 years (median 74 years, range 27-85 years), 101 (67%) were male, 56 had implanted a VVI PM, and 94 patients a DDD PM. Patients were divided into two groups: outflow tract (55 patients) and apical pacing (95 patients). Mean follow-up was 1,231+/-642 days (median 1,158 days, range 9 to 2,694 days), which ended on July 2007. Total mortality was examined with the Kaplan-Meier method to construct overall survival curves. Multivariate Cox proportional hazards regression models were performed. All patients or relatives were contacted personally or by phone. There were no major statistical differences in patient background between the two groups. During follow-up, 18 patients (32%) died in the outflow tract group and 49 (51%) in the apical group (log-rank p=0.02). Cox regression multivariate analysis showed that outflow tract pacing and a low left ventricular ejection fraction (<40%) were the only independent variables with significant correlation with survival (p=0.006 and 0.003, respectively). Outflow tract pacing appears to improve medium- and long-term survival. Prospective randomized trials with a greater amount of patients are necessary to confirm the findings of this study.


A comparison of three methods for the determination of the growth fraction in non-Hodgkin's lymphoma.
The proliferation rate of non-Hodgkin's lymphomas (NHL) was estimated by using 3 different methods. In cell suspension we determined the proportion of cells in cycle with the monoclonal antibody (Mab) Ki-67 and also in S-phase after the incorporation of bromo-deoxyuridine (BrdU) utilizing Mab anti-BrdU. In low grade lymphomas 3.5 +/- 1.6% of the cells were in cycle and 1.2 +/- 0.9% in S-phase, the corresponding values for high grade lymphomas were 22.5 +/- 18.7% and 8.9 +/- 7.8% respectively. Frozen sections of NHL were reacted with an antibody to the transferrin receptor (TR) and Ki67 as markers for proliferative activity. A high number of TR positive cells was found in low grade lymphomas of all histological types, whereas Ki67 positivity correlated closely with grading. With a few exceptions, low grade lymphomas contained less than 25% Ki67 positive cells within the tumour cell population. This observation is relevant to treatment strategies for low grade NHL.


Advances in the Treatment of Neonatal Biliary Disease.
This article discusses current standard of care in neonatal biliary disease, particularly management of biliary atresia and choledochal cysts. It highlights surgical considerations, guidelines for adjuvant therapies, and promising therapeutic options that are under investigation.


Comparative Study of Onion (Allium cepa) and Leek (Allium ampeloprasum): Identification of Organosulphur Compounds by UPLC-QTOF/MS and Anticancer Effect on MCF-7 Cells.
Onion (Allium cepa) and leek (Allium ampeloprasum var. porrum) are common herbs and vegetables found in our daily life. It belongs to the genus Allium, which is usually known for their high antioxidant and anticancer properties. Medical researchers highly recommend the exploitation of herbs and plants as alternative ways in the treatment of cancer. This research was designed to study the anticancer effects of onion and leek extracts on MCF-7 human breast cancer cell. Crude extracts of ethanol, methanol, and water of onion and leek were obtained by maceration. MCF-7 cells were cultured in complete media at 37 °C and subjected to different treatments that involved varying concentrations (10, 50, and 100 μg/mL) of onion and leek extracts for 24, 48, and 72 h of incubation. The percentage of cell viability and the concentration of extracts on MCF-7 cells were determined using MTT assay. The water leek extract proved to be the most effective extract at 50 μg/mL, whereby it showed a significant inhibition ability due to the presence of entadamide A-β-D-glucopyranoside as identified by ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-QTOF/MS). Further studies about the mechanism of both extracts in causing cell death and the determination of the presence of other bioactive compounds in the extracts are needed.


Long-term effect of respiratory training for chronic obstructive pulmonary disease patients at an outpatient clinic: a randomised controlled trial.
To assess the effect of respiratory training (RT) on lung function, activity tolerance and acute exacerbation frequency with chronic obstructive pulmonary disease (COPD). A randomised controlled trial. Outpatient clinic and home of the COPD patients, Zhengzhou City, China. Sixty participants with COPD were randomised into two groups: an intervention group (n = 30) which received the RT in self-management and a control group (n = 30) that received an education program during the study. Pulmonary function, activity tolerance and frequency of acute exacerbation of these COPD patients were evaluated before and after the program. The intervention and control programs were delivered at monthly outpatient clinic visits over a period of 12 months. The pulmonary rehabilitation (PR) program was conducted by a physiotherapist (who delivered RT to the participant over a minimum of 1 h per visit) for the intervention group, whereas the control group received routine health education provided by physiotherapists. The intervention group patients were then instructed to perform exercises at home as taught in the RT at least 5 days per week at home. After 12 months of RT, the lung function and the activity tolerance of the COPD patients in the intervention group were significantly improved and the exacerbation frequency was also decreased. Long-term RT can improve lung function and activity tolerance while decreasing the frequency of acute exacerbation for COPD patients.


Pain on i.v. injection of propofol (ICI 35 868) in emulsion formulation. Short communication.
Pain on injection of three anaesthetic induction agents, thiopentone, methohexitone and propofol (diisopropyl phenol), administered into a vein on the dorsum of the hand or wrist, was studied in 32 premedicated patients undergoing elective surgery. The pain was rated as none, mild or severe. A 1% emulsion formulation of propofol (ICI 35 868) (2 mg kg-1) and methohexitone (2 mg kg-1) induced pain significantly more often, in 100% and 80% of patients, respectively, than thiopentone (4 mg kg-1), 0%. The pain was rated as severe more often in patients receiving propofol (67%, P less than 0.01 vs thiopentone) than in those anaesthetized with methohexitone (20%) or thiopentone (0%). It is concluded that the fat emulsion form of propofol, when injected into a peripheral vein, frequently induces severe pain.


Radiophosphate imaging of regional migratory osteoporosis.
A patient with regional migratory osteoporosis had somewhat unusual features in that there was involvement of the small joints of the foot demonstrable by 99mTc-methylene diphosphonate joint imaging.


Predictive value of cone margins and post-cone endocervical curettage with residual disease in subsequent hysterectomy.
In 51 of 106 patients (48%) residual disease was identified in hysterectomy specimens performed following cervical conization. Invasive squamous cell carcinoma was found in one patient in spite of clear cone margins. Thirty-nine of sixty-three patients (62%) with cervical intraepithelial neoplasia (CIN) involving the inner (endocervical) margin of the cone biopsy had residual disease. When both the inner margin and post-cone endocervical curettage (ECC) were involved, residual disease was present in 24 of 30 (80%) hysterectomy specimens. When the inner margins of the cone were involved with CIN-III and the post-cone ECC was negative, 36% of hysterectomy specimens contained residual disease compared to 88% when post-cone ECC was positive. These findings indicate that post-cone endocervical curettage has significant predictive value with respect to the presence or absence of residual disease in patients with CIN involving the inner margins of the cervical cone.


Prognostic Impact of Number of Organ Invasions in Patients with Surgically Resected Thymoma.
This study aimed to explore the clinical implications and prognostic value of the number of organ/structure invasions (NOI) in patients with thymoma after curative surgical resection. We retrospectively analyzed 306 consecutive Japanese patients with thymoma who underwent curative surgical resection. Tumor invasions of pericardium, mediastinal pleura, phrenic nerve, lung, and venous structures were examined histopathologically. Cases were classified into four subgroups according to NOI: group 0, no tumor invasion; group 1, tumor invasion into single organ/structure; group 2, tumor invasion of two organs/structures; group 3, invasion of three or more organs/structures. Associations with NOI and several clinical characteristics and their prognostic significance were analyzed. Pleural invasion was found in 100 cases (32.7%), lung invasion in 48 cases (15.7%), pericardial invasion in 46 cases (15%), phrenic nerve invasion in 29 (9.5%), and venous invasion in 22 cases (7.2%). NOI was classed as group 0 in 201 cases (65.0%), group 1 in 42 cases (13.7%), group 2 in 20 cases (6.5%), and group 3 in 43 cases (14.1%). Cases with higher NOI showed significantly worse relapse-free survival (RFS) and overall survival (OS). Cox's proportional hazard model analysis also identified NOI as a prognostic factor affecting RFS and OS. Cases with higher NOI of thymoma after radical surgical resection showed significantly worse recurrence rates and survival.


Oral susceptibility of aedine and culicine mosquitoes (Diptera: Culicidae) to Batai Orthobunyavirus.
A number of zoonotic mosquito-borne viruses have emerged in Europe in recent decades. Batai virus (BATV), a member of the genus Orthobunyavirus, is one example of a relatively newly emerged mosquito-borne virus, having been detected in mosquitoes and livestock. We conducted vector competency studies on three mosquito species at a low temperature to assess whether Aedes and Culex mosquito species are susceptible to infection with BATV. Colonised lines of Aedes aegypti and Culex pipiens and a wild-caught species, Aedes detritus, were orally inoculated with BATV strain 53.2, originally isolated from mosquitoes trapped in Germany in 2009. Groups of blood-fed female mosquitoes were maintained at 20 °C for 7 or 14 days. Individual mosquitoes were screened for the presence of BATV in body, leg and saliva samples for evidence of infection, dissemination and transmission, respectively. BATV RNA was detected by reverse transcription-PCR, and positive results confirmed by virus isolation in Vero cells. Aedes detritus was highly susceptible to BATV, with an infection prevalence of ≥ 80% at both measurement time points. Disseminated infections were recorded in 30.7-41.6% of Ae. detritus, and evidence of virus transmission with BATV in saliva samples (n = 1, days post-infection: 14) was observed. Relatively lower rates of infection for Ae. aegypti and Cx. pipiens were observed, with no evidence of virus dissemination or transmission at either time point. This study shows that Ae. detritus may be a competent vector for BATV at 20 °C, whereas Ae. aegypti and Cx. pipiens were not competent. Critically, the extrinsic incubation period appears to be ≤ 7 days for Ae. detritus, which may increase the onward transmissibility potential of BATV in these populations.


3D-Printed Carbon Nanoelectrodes for In Vivo Neurotransmitter Sensing.
Direct laser writing, a nano 3D-printing approach, has enabled fabrication of customized carbon microelectrode sensors for neurochemical detection. However, to detect neurotransmitters in tiny biological organisms or synapses, submicrometer nanoelectrodes are required. In this work, we used 3D printing to fabricate carbon nanoelectrode sensors. Customized structures were 3D printed and then pyrolyzed, resulting in free-standing carbon electrodes with nanotips. The nanoelectrodes were insulated with atomic layer deposition of Al2O3 and the nanotips were polished by a focused ion beam to form 600 nm disks. Using fast-scan cyclic voltammetry, the electrodes successfully detected stimulated dopamine in the adult fly brain, demonstrating that they are robust and sensitive enough to use in tiny biological systems. This work is the first demonstration of 3D printing to fabricate free-standing carbon nanoelectrode sensors and will enable batch fabrication of customized nanoelectrode sensors with precise control and excellent reproducibility.


On-line monitoring of a frontal chromatographic separation using inductively coupled plasma atomic emission spectroscopy.
A test array is described employing a destructive analytical technique for the long-term monitoring of an industrial-scale separation process. As an example, we chose frontal chromatography as the separation and ICP/AES as the analytical method. The feed solution of the process was conveyed by a process pump via the separation unit to a sample station, where a small portion was diverted and transported by a roller pump into the spectrometer. We equipped our array with different loops for operating the process, calibrating the instrument and verifying the calibration. We obtained identical results for the different loops by absorbing the pulsation of the process pump and arranging for identical suction lines of the spectrometer pump. Based on the results, we redesigned the sample station for a technical application using only commercially available parts.


Postprostatectomy urinary infection: cystourethrographic study.
Postoperative cystourethrography can be valuable in the diagnosis and management of urinary tract infection and other postprostatectomy complications. The authors have studied 50 patients and recommend voiding cystourethrography prior to endoscopic assessment of bladder outlet resistance. In addition, urinary infection may complicate a clear-cut obstructive lesion and present as a mixture of irritative and obstructive symptoms. The correlation between symptoms and the obstructive lesion is only 40 per cent. There is obviously a need for a more objective evaluation by means of cystourethrography.


Selective modulation of P-glycoprotein activity by steroidal saponines from Paris polyphylla.
Bio-guided fractionation of the roots of Paris polyphylla (Trilliaceae), based on inhibition of P-glycoprotein-mediated daunorubicin efflux in K562/R7 cell line, led to isolation and identification of the three saponins 3-O-Rha(1-->2)[Ara(1-->4)]Glc-pennogenine, gracillin and polyphyllin D, and the two ecdysteroids 20-hydroxyecdysone and pinnatasterone. These compounds were tested for multidrug reversion on P-glycoprotein (ABCB1) with both drug-selected and transfected cell lines, and also on Breast Cancer Resistance Protein (BCRP/ABCG2). By contrast to a weak efficiency on BCRP, the three saponins displayed significant effects as inhibitors of P-glycoprotein-mediated drug efflux.


Frequent polymerase errors observed in a restricted area of clones derived from the attachment (G) protein gene of respiratory syncytial virus.
Sequence analysis of a large number of clones derived from the carboxy-terminal one-third of the attachment (G) protein gene of subgroup A respiratory syncytial viruses revealed a region very prone to polymerase errors which resulted mainly in frameshifts because of the insertion or deletion of adenosine residues in some but not all runs of such residues. Such mutations were detected in 14% of clones derived from mRNA, 58% of clones derived from genomic-sense RNA, and 50% of clones derived from in vitro-transcribed RNA. This phenomenon appears to be dependent on the template sequence.


Behavioral Welfare Research for the Management of Sanctuary Chimpanzees (Pan troglodytes).
Chimp Haven is a sanctuary for chimpanzees retired from biomedical research, rescued from the pet trade, or re-homed after other organizations could no longer care for them. To provide optimal care for over 300 chimpanzees, Chimp Haven's animal care team includes experts in behavioral science, veterinary treatment, and husbandry practices. To aid these teams in making routine welfare management decisions, a system of behavioral metrics provides objective data to guide decisions and track outcomes. Chimp Haven has built and piloted seven behavioral metric protocols over the past 5 years to provide staff with an objective and comprehensive picture of the chimpanzees' behavioral welfare. The data from behavioral observations, staff surveys, and routine staff documentation are analyzed and processed through Google Forms, ZooMonitor, Microsoft Power Bi, Microsoft Excel, and R. Each metric assists staff in making data-based decisions regarding the management of captive chimpanzees related to abnormal behavior, hair loss, wounding, social relationships, positive reinforcement training and overall wellness. In this article, we explore examples of each metric and how they have been utilized to monitor and make decisions for both social groups of chimpanzees as well as individuals. These metrics can be collected and shared easily in an understandable format, which may provide an important framework for others to follow to enable the tracking of welfare for other sanctuaries, non-human primates, as well as other species.


Initial experience with laparoscopic and robotic surgery for the treatment of periampullary tumours: single institution experience with the first 30 consecutive cases.
Concerns have been raised about the safety of minimally invasive surgery (MIS) for pancreatoduodenectomy (PD) during the early learning phase. In this study, we present our initial experience with MIS for periampullary tumours. Retrospective review of the first 30 consecutive patients who underwent laparoscopic (LS)/robotic surgery (RS) for periampullary tumours between 2014 and 2017. Twenty-seven patients underwent PD, including three total pancreatectomies (TPs) and three underwent palliative bypasses. Twenty underwent LS, of which 18 were hybrid PDs, including two TPs and two bypasses. Ten patients underwent RS, of which nine were PDs, including one TP and one bypass. Five of 10 RSs were totally MIS procedures. There were four PDs with venous resection, of which three were by RS. There were four (13.3%) open conversions all in the LS cohort. There were five (16.7%) major (>grade 2) morbidities, including three pancreatic fistulas (two grade B and one grade C). There was no 30-day and one (3.3%) 90-day mortality. Comparison between RS and LS demonstrated that RS had a higher likelihood of being completed via totally MIS (five (50%) versus 0, P = 0.002), tended to have a shorter post-operative stay (eight (range 6-36) versus 14.5 (range 6-62) days, P = 0.058) but tended to be associated with a longer operation time (670 (range 500-930) versus 577 (range 235-715) min, P = 0.056). Our initial experience demonstrated that both LS and RS can be safely adopted for the treatment of periampullary tumours. The learning curve for RS seemed to be shorter than LS as we could transition more quickly from hybrid PDs to totally MIS safely.


Three-dimensional reconstruction of nucleolar components by electron microscope tomography.
The nucleus is a complex volume constituted of numerous subcompartments in which specific functions take place due to a specific spatial organization of their molecular components. To understand how these molecules are spatially organized within these machineries, it is necessary to investigate their three-dimensional organization at high resolution. To reach this goal, electron tomography appears to be a method of choice; it can generate tomograms with a resolution of a few nanometers by using multiple projections of a tilted section several hundred to several thousand nanometers in thickness imaged by transmission electron microscopy (TEM).Specific identification of molecules of interest contained within such thick sections requires their specific immunocytochemical labelling using electron-dense markers. We recently demonstrated that electron tomography of proteins immunostained with nanogold particles before embedding, and subsequently amplified with silver, was very fruitful due to the inherently high spatial resolution of the medium-voltage scanning and transmission electron microscope (STEM). Here we describe this approach, which is very efficient for tracing the 3D organization of proteins within complex machineries by using antibodies raised against one of the proteins, or against GFP to analyse GFP-tagged proteins.


Parathyroid carcinoma.
Parathyroid carcinoma is a rare tumor with an incidence of 0.5 to 4%. Preoperative differentiation from benign adenoma is very difficult. Several features, though nonspecific, have been used in differentiating parathyroid carcinoma from the adenoma. A retrospective analysis during the period of nine years, four cases of parathyroid carcinoma were diagnosed on the basis of per-operative local invasion and on histological evidence of capsular invasion and vascular invasion. We have different observations to make. Diagnosis of parathyroid carcinoma which was done on the basis of intra operative suspicion only. One patient died on 6th post operative day due to development of pancreatitis. At the follow-up of two years there was no local recurrence or distant metastasis. It is preferable to have a high index of suspicion for parathyroid carcinoma when these features are present than to miss the opportunity for surgical cure by failing to consider it in the differential diagnosis.


Tip-induced nanoreactor for silicate.
Nanoscale scientific issues have attracted an increasing amount of research interest due to their specific size-effect and novel structure-property. From macro to nano, materials present some unique chemical reactivity that bulk materials do not own. Here we introduce a facile method to generate silicate with nanoscale control based on the establishment of a confined space between a meso/nanoscale tungsten tip and a smooth silica/silicon substrate. During the process, local water-like droplets deposition can be obviously observed in the confinement between the Si/SiO2 surfaces and the KOH-modified tungsten tip. By the combination of in-situ optical microscopy and Raman spectroscopy, we were able to take a deep insight of both the product composition and the underlying mechanism of such phenomena. It was indicated that such nanoreactor for silicate could be quite efficient as a result of the local capillarity and electric field effect, with implications at both nano and meso scales.


A Study Protocol to Increase Engagement in Evidence Based Hospital and Community Based Care Using a Serious Injection Related Infections (SIRI) Checklist and Enhanced Peer for Hospitalized PWID (ShaPe).
With the opioid crisis, surging methamphetamine use, and healthcare disruptions due to SARS-CoV-2, serious injection related infections (SIRIs), like endocarditis, have increased significantly. Hospitalizations for SIRI provide a unique opportunity for persons who inject drugs (PWID) to engage in addiction treatment and infection prevention, yet many providers miss opportunities for evidence-based care due to busy inpatient services and lack of awareness. To improve hospital care, we developed a 5-item SIRI Checklist for providers as a standardized reminder to offer medication for opioid use disorder (MOUD), HIV and HCV screening, harm reduction counseling, and referral to community-based care. We also formalized an Intensive Peer Recovery Coach protocol to support PWID on discharge. We hypothesized that the SIRI Checklist and Intensive Peer Intervention would increase use of hospital-based services (HIV, HCV screening, MOUD) and linkage to community-based care: PrEP prescription, MOUD prescription, and related outpatient visit(s). This is a feasibility study and randomized control trial of a checklist and intensive peer intervention for hospitalized PWID with SIRI admitted to UAB Hospital. We will recruit 60 PWID who will be randomized to one of 4 groups (SIRI Checklist, SIRI Checklist + Enhanced Peer, Enhanced Peer, and Standard of Care). Results will be analyzed using a 2x2 factorial design. We will use surveys to collect data on drug use behaviors, stigma, HIV risk, and PrEP interest and awareness. Our primary outcome of feasibility will include the ability to recruit hospitalized PWID and retain them in the study to determine post-discharge clinical outcomes. Additionally, we will explore clinical outcomes using a combination of patient surveys and electronic medical record data (HIV, HCV testing, MOUD and PrEP prescriptions).This study is approved by UAB IRB #300009134. This feasibility study is a necessary step in designing and testing patient-centered interventions to improve public health for rural and Southern PWID. By testing low barrier interventions that are accessible and reproducible in states without access to Medicaid expansion and robust public health infrastructure, we aim to identify models of care that promote linkage and engagement in community care. NCT05480956.


Changes in volatile compounds of mouse urine as it ages: their interactions with water and urinary proteins.
Mice release a variety of chemical signals, particularly through urine, which mediate social interactions and endocrine function. Studies have been conducted to investigate the stability of urinary chemosignals in mice. Neuroendocrine and behavioral responses of mice to urine samples of male and female conspecifics which have aged for different amounts of time have been examined, demonstrating that the quality and intensity of signaling molecules in urine change over time. In this study, we monitored changes in volatile organic compounds (VOCs) released from male and female mouse urine following aging the urine samples. Substantial amounts of some VOCs were lost during the aging process of urine, whereas other VOCs increased. Considerable portions of the VOCs which exhibited the increased release were shown to have previously been dissolved in water and subsequently released as the urine dried. We also demonstrated that some VOCs decreased slightly due to their binding with the major urinary proteins (MUPs) and identified MUP ligands whose headspace concentrations increased as the urine aged. Our results underscore the important role of MUPs and the hydration status in the release of VOCs in urine, which may largely account for the changes in the quality and intensity of urinary signals over time.


Toxicity of Porella chilensis sesqui- and diterpenoids against larvae of the corn pest Spodoptera frugiperda (J.E. Smith) (Lepidotera: Noctuidae).
Porella, the largest genus of the family Porellaceae (Hepaticae) is widespread in the tropical and subtropical regions of South America. Most Porella species are rich sources of sesqui- and diterpenoids, many of which show interesting biological activities. Secondary metabolites produced by plants can interact with insects and act as antifeedants and growth regulators affecting hormone and nervous systems as well as stomach and muscle tissues. A previous chemical investigation of a Patagonian collection of Porella chilensis yielded sesqui- and diterpenoids that were now evaluated for their effects against Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae), a serious pest affecting corn crops mainly in the Americas. Four pinguisanes (1-4), three fusicoccanes (5-7), and one aromadendrane (8) from P. chilensis displayed larvicidal activity against S. frugiperda when incorporated to the larval diet at 100 and 200 μg/g of diet with a significant decrease in the larval growing rate. The observed effects were in part produced by severe alterations of the epithelial cells of the midgut as indicated by our histological studies.


Syphacia obvelata infections and reproduction of male domestic mice Mus musculus domesticus on a sub-Antarctic Island.
The reproductive activity of feral male mice on an island of the sub-Antarctic Kerguelen archipelago was influenced by biological factors depending on periods within the breeding season. After having controlled host reproductive activity indices for body size, i.e. age, and body condition effects, Syphacia obvelata prevalence did not vary with host reproductive status or age either during the beginning or the middle-end of the reproductive season. Considering the beginning of the breeding season, worm abundance was more pronounced in males the year following a strong winter crash of the population than in years when high over wintering survival occurred. During the middle-end of the breeding season, males with the highest reproductive status were more infected than males with a lower reproductive status in years when oldest individuals dominated the population. It is suggested that this situation was due to an endocrine related increased host susceptibility partly influenced by a change in the age structure of the population, and that an increase in worm transmission was not directly related to male activity concurrent with reproductive status, nor to population density.


Combined effects of particle size and humic acid corona on the aggregation kinetics of nanoplastics in aquatic environments.
Nanoplastics (NPs) contaminant in aquatic environments is one of the pressing environmental concerns globally. However, the combined effects of particle size and humic acid (HA) corona on the aggregation behavior of NPs have not been revealed yet. Therefore, this study explored the influence of HA corona on the aggregation kinetics of NPs with three different particle sizes under various water quality conditions. Results showed that in the absence of HA corona, the aggregation kinetic processes of all the three NPs were affected by the repulsive force originating from the hydration layer. Moreover, the smaller the particle size, the more obvious the effect. HA corona played a steric hindrance role for all the three NPs based on the extended-Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory in monovalent solutions, resulting in the impediment of aggregation. Whereas, in divalent solutions, the HA corona of 100 and 200 nm NPs experienced three stages: deformation, electrostatic-patch and bridging; while that of 40 nm NPs underwent electrostatic-patch and steric hindrance. The larger number of HA molecules distributed on 100 and 200 NPs surfaces led to more interactions with Ca2+ and NPs, which was the key factor for HA corona to play more diverse roles. According to the two dimension correlation spectroscopy analysis (2D-COS), the structural change in the interaction between HA and NPs was that the aromatic ring of NPs took precedence, followed by the carbonyl groups of HA. This study provided new insights into the combined effects of HA corona and particle size on the aggregation kinetics of NPs and established a theoretical foundation for predicting and assessing the transport and fate of NPs.


Preliminary Psychometrics of the Knowledge and Attitudes Toward SBAR Instrument (KA-SBAR).
When measuring new practice approaches for improving patient safety in the clinical setting, researchers need instruments with evidence of reliability and validity. The purpose of this analysis was to examine the reliability and validity of an instrument to assess knowledge and attitudes toward communication using situation-background-assessment-recommendation (SBAR; KA-SBAR). This psychometric analysis was conducted with data from an interprofessional simulation-based learning experience with doctor of nursing practice students (n = 19) and physical therapy students (n = 52). Internal consistency reliability and construct validity tests including factor analysis for the KA-SBAR were conducted. The KA-SBAR instrument had adequate internal consistency reliability and evidence of construct validity, including identification of two factors that explained 70% of the instrument's variance. However, there may be a ceiling effect of scores, making it difficult to show change. The KA-SBAR instrument may be useful in assessing clinicians' perceptions of SBAR communication in education and practice settings. When selecting data collection measures, nurses need to carefully consider the purpose of the measure and evidence of the instrument's reliability and validity. Educators need to consider the clinical expertise of the students in designing challenging simulations to advance learning.


Lewis acid- and organocatalyst-cocatalyzed multicomponent reactions of 2-alkynylbenzaldehydes, amines, and ketones.
One-pot combination of silver triflate and proline catalysis is highly effective for the synthesis of 1,2-dihydroisoquinoline derivatives via multicomponent reactions of 2-alkynylbenzaldehydes, amines, and ketones.


Prenatal ethanol and stress in mice: 1. Pup behavioral development and maternal physiology.
On days 12 to 17 of pregnancy, B6D2F1 mice were pair-fed liquid diets containing either 25% ethanol-derived calories or an isocaloric amount of maltose-dextrin. During this period, half the mice in each dietary condition also underwent two daily one-hour periods of restraint stress. A fifth group, given lab chow and water ad lib, was left undisturbed throughout gestation. Neither treatment affected offspring body weight on days 22 or 32 postconception, but undernutrition produced by the pair feeding procedure reduced day 32 body weight in all groups relative to the ad lib-fed group. Both prenatal ethanol and pair feeding led to delayed neurobehavioral development on day 32, while prenatal stress significantly reduced the degree of developmental delay caused by these factors. In a second study, restraint stress significantly reduced blood alcohol concentrations in pregnant dams on day 15 of gestation while elevating plasma corticosterone concentrations, and this elevation was consistent regardless of the dietary condition of the dam. The pair feeding procedure also produced corticosterone elevations but the effect of ethanol was not significant. These results suggest that prenatal stress in the presence of other physiological insults may act to counter the actions of those insults.


Feeding biology of Diplogasteritus nudicapitatus and Rhabditis curvicaudata (Nematoda) related to food concentration and temperature, in sewage treatment plants.
The feeding biology of two bacterivorous nematodes found in percolating filter-bed sewage treatment plants were investigated in relation to food supply and temperature at all developmental stages. Temperature profoundly affected feeding activity and ingestion rates. As temperature increased ingestion rates increased. The larger species, Rhabditis curvicaudata possessed lower rates of pharyngeal pulsation than the small species Diplogasteritus nudicapitatus. R. curvicaudata reduced feeding activity as bacterial density fell from 8x109 cells ml-1 to 5x107 cells ml-1, below which it ceased feeding. D. nudicapitatus pumped continuously at a more or less constant rate irrespective of food density. The evolutionary and ecological aspects of these two patterns of feeding behaviour are discussed.


Speech adaptation: an aerodynamic study of adults with a childhood history of articulation defects.
Three groups of subjects were studied; former lispers, persons with a history of /l/ or /r/ distortion, and normal subjects with no history of speech defects. All were normal-sounding adult speakers of English at the time of participation. Subjects were asked to wear an experimental removable dental prosthesis that provided 4 mm of thickness in the alveolar region. Measurements of oral air flow and intraoral pressure during the reading of sentence material were made, with the focus on the consonants /s/ and /t/. The sibilant /s/ was experienced as the greatest problem for speech adaptation, regardless of the type of former articulation defect. Both groups of subjects with a history of articulation defects showed evidence of slower adaptation and use of compensatory strategies for /s/. They tended as a group to have the same minimum airflow values for /s/ after 2 weeks of practice speaking with the prosthesis as after 1 day of practice. Aerodynamic calculation of the size of the constriction for /s/ also showed little or no change for most of the former speech-defective subjects. Evidence based on intraoral pressure indicated that particular effort was expended for /s/ even after 2 weeks of practice in speaking with the prosthesis.


Rapid evolution of a unique family of primate ribonuclease genes.
We have traced the rapid molecular evolution of eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP), two host defense proteins that are members of the mammalian ribonuclease gene family. The EDN/ECP gene pair arose from a recent duplication event that occurred after the divergence of New World and Old World monkeys. Since duplication, the genes encoding EDN and ECP have accumulated non-silent mutations at rates exceeding those of all other functional coding sequences studied in primates, while retaining both the structural and catalytic components required for ribonuclease activity. These results suggest that both EDN and ECP may be responding to unusual evolutionary constraints, which has prompted a reexamination of their physiologic function.


A MRS study of metabolic alterations in the frontal white matter of major depressive disorder patients with the treatment of SSRIs.
Proton magnetic resonance spectroscopy provides a non-invasive technology to study brain metabolite levels in vivo, which can be used to measure biochemical compounds or metabolite concentrations in circumscribed brain regions. Previous research has highlighted the role of glial cells in brain white matter. It has been assumed that antidepressant treatment with SSRIs not only affects neurons, but also activates glial cells. This study focused on the observation of any potential changes in the metabolite levels of the ventral prefrontal white matter in major depressive disorder (MDD) patients who have received antidepressant treatment. 17 female patients diagnosed as MDD according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria with the scores of 18 and above on the 24-item Hamilton Depression Rating Scale (HDRS) were recruited. MRS studies were performed on a 3.0 T MR system, single voxel PRESS spectroscopy with chemical-shift selective saturation water suppression. The volume of interest was localized at the bilateral ventral prefrontal white matter regions (voxel size: 2 × 2 × 2 mm(3)). The spectral data analysis was performed by using the instrument manufacturer supplied software. The bilateral ventral prefrontal white matter of MDD patients showed significantly lower Cho/Cr (p < 0.05) before receiving treatment. The HDRS, as the indicator of treatment response, showed a significant decrease in patients who had gone through 12 weeks treatment (p < 0.01). The bilateral Cho/Cr values of post-treatment patients were increased significantly compared to that of pre-treatment (p < 0.05). The alteration of ventral prefrontal white matter metabolite levels are likely involved in MDD pathophysiology and imply a crucial role of white matter in MDD.


Human Immunodeficiency Virus-1 Subtype-C Genetically Diversify to Acquire Higher Replication Competence in Human Host with Comorbidities.
Unusual disease progression is observed in the HIV-1 infected patients who are either coinfected with Mycobacterium tuberculosis (Mtb) or concomitantly on intravenous drug use (IDU). The mechanism involved in the breakdown of host immune defense and the synergistic effect in both the conditions are still not well understood. In this study, we aimed to highlight the emergence of genetically diversified variants of virus in these two cohorts among HIV-1 subtype-C infected population from a Northern state of India. A cross-sectional study was performed on treatment-naïve HIV-1 subtype-C infected individuals constituting three different cohorts of HIV-1 monoinfected, HIV-1-M. tuberculosis (HIV-TB) coinfected, and HIV-1 infected individuals on substance abuse (HIV-IDU) for acquisition of genetic alterations in terms of frequency of drug resistance (DR) mutations in reverse transcriptase gene. The data reveal a significantly higher viral load, higher death rate, and higher frequency of major DR mutations in the genome of viral isolates from HIV-TB and HIV-IDU cohorts as compared with HIV monoinfected. Majority of the mutations found in the HIV-TB coinfected and HIV-IDU cohorts conferred high level of resistance to the first-line treatment regimen (Lamivudine with Tenofovir or zidovudine or Abacavir and Nevirapine or Efavirenz). Our findings support the hypothesis that the HIV-1 evolve while replicating in the host with Mtb coinfection or substance abuse, with the emergence and accumulation of genetically diversified quasi-species. Further studies are warranted to understand the association of such genetic variations with increased replication competence and faster rate of disease progression in such individuals.


Structuring total angular momentum of light along the propagation direction with polarization-controlled meta-optics.
Recent advances in wavefront shaping have enabled complex classes of Structured Light which carry spin and orbital angular momentum, offering new tools for light-matter interaction, communications, and imaging. Controlling both components of angular momentum along the propagation direction can potentially extend such applications to 3D. However, beams of this kind have previously been realized using bench-top setups, requiring multiple interaction with light of a fixed input polarization, thus impeding their widespread applications. Here, we introduce two classes of metasurfaces that lift these constraints, namely: i) polarization-switchable plates that couple any pair of orthogonal polarizations to two vortices in which the magnitude and/or sense of vorticity vary locally with propagation, and ii) versatile plates that can structure both components of angular momentum, spin and orbital, independently, along the optical path while operating on incident light of any polarization. Compact and integrated devices of this type can advance light-matter interaction and imaging and may enable applications that are not accessible via other wavefront shaping tools.


Mould and grass pollen allergy as risk factors for childhood asthma in Zaragoza, Spain.
Examine the prevalence of asthma and associated predictive factors in a group of 468 students. A descriptive, cross-sectional observational study in a randomly selected population of 468 children aged 10-12, in the city of Zaragoza. We used the ISAAC questionnaire on asthma completed by children under supervision of the investigators. We assessed the genetic risk (family history of asthma) and environmental risks. The risk for atopy was assessed by the presence of positive skin prick tests. 25.3% of the children had symptoms consistent with asthma in the city of Zaragoza. Among them 33.1% reported a history of asthma in close relatives (OR=1.78, p<0.001). The history of hospitalisations for lower respiratory tract illness was strongly associated with the presence of asthma (OR=6.72, p<0.0001). Positive skin tests to Alternaria (OR=2.00, p<0.0001) and grass pollen (OR=1.76, p<0.001) were predictors of asthma. 63.6% of asthmatic children had presented clinical rhinitis in the previous 12 months, compared with 32% of non-asthmatics, and this difference was statistically significant (OR=3.89, p<0.0001). 47% of asthmatics presented with or previously had eczema, whereas only 26.9% of non-asthmatics presented with or previously had these types of lesions (p<0.0001). The following are predictors of asthma: History of hospital admissions for lower respiratory tract illness, presence of rhinitis and/or eczema, positive prick test for certain aeroallergens, especially Alternaria and grass pollen, and family history of asthma.


In search of decoy/guardee to R genes: deciphering the role of sugars in defense against Fusarium wilt in chickpea.
Plant responses are coordinately controlled by both external and internal signals. Apt perception of pathogen attack and its appropriate conversion to internal signals ultimately determine the outcome of innate immunity. The present review predicts the involvement of unconventional 'Guard/Decoy Model' in chickpea-Fusarium encounter. Rapid alkalinization factor is predicted to act as initial 'Gatekeeper decoy' counteracting fungal entry. Phospholipases and cystatins probably function as 'Guardees' being shielded by R gene(s). Serine Threonine Kinases decodes external pathogenic signals to in planta defense alarms. 14.3.3 provides clues to the wilt mechanism. The versatile sugars serve as signal generators and transmitters maintaining intra and inter cellular connectivity during stress.


Prediction of susceptibility to an irritant response by transepidermal water loss.
The roles of the natural permeability of the stratum corneum to water, and the changes in that permeability effected by a single patch test, were investigated as parameters to predict the susceptibility of the skin to repeated exposures of an irritant. One site on the forearm skin of 27 non-atopic healthy subjects was exposed to a 0.5% concentration of sodium lauryl sulphate by a single occlusive 24-h patch. Another site was exposed to a twice daily 4-day repeated occlusive patch with the same irritant solution. The effects were evaluated by transepidermal water loss measurements made prior to the applications (baseline) on day 1 (BASE), following the single 24-h patch on day 2 (SINGL), and following the 4-day repeated applications on day 5 (REPET). Individuals with higher BASE had higher SINGL (R = 0.80, P less than 0.001) and higher REPET (R = 0.76, P less than 0.001). There was also a significant linear correlation between SINGL and REPET (R = 0.63, P less than 0.001). Multiple linear regression analysis of results, however, indicated that a high baseline TEWL is better indication of an individual's increased susceptibility (high REPET) to weak irritants than a high TEWL value following a single 24-h patch test. Baseline TEWL may therefore be used as a reasonably accurate preliminary "predictive" screening test for susceptibility to irritants.


North Carolina's 2022-2026 Perinatal Health Strategic Plan: Addressing Perinatal Health Inequities Across the Life-Course.
North Carolina's Perinatal Health Equity Collective promotes the implementation of the 2022-2026 Perinatal Health Strategic Plan, building off its 2016-2020 predecessor. Through its overarching goals, the plan recognizes that reducing perinatal health inequities requires improving health care, strengthening families and communities, and addressing social, racial, and economic inequities across the life-course.


Evaluation of eight commercial kits for Helicobacter pylori IgG antibody detection.
Eight commercial kits and an in-house ELISA for detection of IgG antibodies against Helicobacter pylori were evaluated for their use in diagnosis of H. pylori infection and in epidemiological research: Helico-GTM (Porton-Cambridge), G. A. P. test (Bio-Rad), H. pylori antibodies ELISA (Biometra), Anti-H. pylori IgG EIA (Roche), 2nd generation H. pylori EIA (Roche), Anti-H. pylori MTP-assay (Roche), Pylori stat test kit (Whittaker), Pyloriset latex agglutination kit (Orion), and the in-house ELISA based on heat-stable antigens. Fifty-four patients with dyspepsia (31 H. pylori positive by culture or microscopy) and 68 asymptomatic persons were tested. Sensitivities for the eight kits were 71%, 77%, 90%, 84%, 87%, 94%, 90%, 87%, and 87%, specificities were 74%, 65%, 74%, 74%, 83%, 83%, 70%, 65%, and 65%, respectively. For epidemiological use the estimated seroprevalence varied within approximately 15% in all age groups. Sensitivities and specificities obtained in different studies reveal as great differences in the results with the same kit as between results obtained with different kits in the same study. Kits with the highest sensitivities tend to be the same in all studies. It is therefore more important to test a kit in the population to which it is to be applied than to choose a specific kit.


Asthma severity, psychophysiological indicators of arousal, and immune function in asthma patients undergoing biofeedback-assisted relaxation.
Asthma is characterized by airway hyper-responsiveness, inflammation, and reversible obstruction. Respiratory tract infection, allergies, air pollution, and psychosocial factors impact the severity and frequency of asthma symptoms. Pharmacotherapy and self-care are the major components in the management of asthma, but behavioral interventions also have the potential to affect asthma morbidity. We conducted a small, randomized controlled study, examining the effects of biofeedback-assisted relaxation in 16 nonsmokers with nonsteroid-dependent mild asthma. Data were collected on asthma symptoms, pulmonary function, indicators of arousal, and cellular immune factors. The trained group evidenced a decrease in forehead muscle tension in comparison to the controls, but no changes in peripheral skin temperature. Decreases in asthma severity and bronchodilator medication usage for the experimental group were observed. Pulmonary function testing revealed a significant difference between groups in FEV1/FVC at posttest, with the E group having a higher ratio than the controls. The cellular immune data showed no significant group differences in total white blood cell or lymphocyte counts, but decreases over time were observed. Significant differences were observed in the numbers of neutrophils and basophils in the trained group compared to controls, which supports the concept of decreased inflammation. Results of delayed-type hypersensitivity skin testing suggested enhanced function, but they were not conclusive. These findings, though limited by size of population, suggest a positive effect of biofeedback-assisted relaxation in young, nonsteroid-dependent asthmatics. The mechanisms underlying linkages between psychological, behavioral, and immune responses in asthma require further study.


On the influence of various physicochemical properties of the CNTs based implantable devices on the fibroblasts' reaction in vitro.
Coating the material with a layer of carbon nanotubes (CNTs) has been a subject of particular interest for the development of new biomaterials. Such coatings, made of properly selected CNTs, may constitute an implantable electronic device that facilitates tissue regeneration both by specific surface properties and an ability to electrically stimulate the cells. The goal of the presented study was to produce, evaluate physicochemical properties and test the applicability of highly conductible material designed as an implantable electronic device. Two types of CNTs with varying level of oxidation were chosen. The process of coating involved suspension of the material of choice in the diluent followed by the electrophoretic deposition to fabricate layers on the surface of a highly biocompatible metal-titanium. Presented study includes an assessment of the physicochemical properties of the material's surface along with an electrochemical evaluation and in vitro biocompatibility, cytotoxicity and apoptosis studies in contact with the murine fibroblasts (L929) in attempt to answer the question how the chemical composition and CNTs distribution in the layer alters the electrical properties of the sample and whether any of these properties have influenced the overall biocompatibility and stimulated adhesion of fibroblasts. The results indicate that higher level of oxidation of CNTs yielded materials more conductive than the metal they are deposited on. In vitro study revealed that both materials were biocompatible and that the cells were not affected by the amount of the functional group and the morphology of the surface they adhered to.


Upregulation of proinflammatory proteins through NF-kappaB pathway by shed membrane microparticles results in vascular hyporeactivity.
Microparticles are membrane vesicles with procoagulant and proinflammatory properties released during cell activation, including apoptosis. The present study was designed in dissecting the effects evoked by microparticles on vascular reactivity. Microparticles from either apoptotic T lymphocytic cells or from plasma of diabetic patients with vascular complications induced vascular hyporeactivity in response to vasoconstrictor agents in mouse aorta. Hyporeactivity was reversed by nitric oxide (NO) synthase plus cyclooxygenase-2 inhibitors, and associated with an increased production of vasodilatory products such as NO and prostacyclin. Microparticles induced an upregulation of proinflammatory protein expressions, inducible NO-synthase and cyclooxygenase-2, mainly in the medial layer of the vessels as evidenced by immunochemical staining. In addition, microparticles evoke NF-kappaB activation probably through the interaction with the Fas/Fas Ligand pathway. Finally, in vivo treatment of mice with lymphocyte-derived MPs induces vascular hyporeactivity, which was reversed by the combination of NO and cyclooxygenase-2 inhibitors. These data provide a rationale to explain the paracrine role of microparticles as vectors of transcellular exchange of message in promoting vascular dysfunction during inflammatory diseases.


Functional integration of skeletal traits: an intraskeletal assessment of bone size, mineralization, and volume covariance.
Understanding the functional integration of skeletal traits and how they naturally vary within and across populations will benefit assessments of functional adaptation directed towards interpreting bone stiffness in contemporary and past humans. Moreover, investigating how these traits intraskeletally vary will guide us closer towards predicting fragility from a single skeletal site. Using an osteological collection of 115 young adult male and female African-Americans, we assessed the functional relationship between bone robustness (i.e. total area/length), cortical tissue mineral density (Ct.TMD), and cortical area (Ct.Ar) for the upper and lower limbs. All long bones demonstrated significant trait covariance (p < 0.005) independent of body size, with slender bones having 25-50% less Ct.Ar and 5-8% higher Ct.TMD compared to robust bones. Robustness statistically explained 10.2-28% of Ct.TMD and 26.6-64.6% of Ct.Ar within male and female skeletal elements. This covariance is systemic throughout the skeleton, with either the slender or robust phenotype consistently represented within all long bones for each individual. These findings suggest that each person attains a unique trait set by adulthood that is both predictable by robustness and partially independent of environmental influences. The variation in these functionally integrated traits allows for the maximization of tissue stiffness and minimization of mass so that regardless of which phenotype is present, a given bone is reasonably stiff and strong, and sufficiently adapted to perform routine, habitual loading activities. Covariation intrinsic to functional adaptation suggests that whole bone stiffness depends upon particular sets of traits acquired during growth, presumably through differing levels of cellular activity, resulting in differing tissue morphology and composition. The outcomes of this intraskeletal examination of robustness and its correlates may have significant value in our progression towards improved clinical assessments of bone strength and fragility.


[Neurochemical mechanisms of morphine action on the function of neurons in the midbrain reticular formation].
The effect of microiontophoretically applied morphine and its interactions with the effect of microiontophoretic applications of either acetylcholine (ACh) or 5-hydroxytryptamine (5-HT) were studied in single neurons of the midbrain RF in immobilized rats. Morphine altered the firing rate of the majority of neurons: 39% neurons were excited, 16%-inhibited. Morphine reduced or blocked reactions of most (67%) neurons to 5-HT but had no effect on their reactions to ACh (86% of neurons). The findings suggest that interaction between morphine and sezotoninergic structures of the brain plays a more important role in mechanism of morphine central action than the interaction between morphine and cholinergic systems.


A nanofiber membrane maintains the quiescent phenotype of hepatic stellate cells.
Hepatic stellate cells (HSC) play a major role in the progression of liver fibrosis. The aim of our study was to investigate whether rat HSC cultured on a nanofiber membrane (NM) retain their quiescent phenotype during both short- and long-term culture and whether activated HSC revert to a quiescent form when re-cultured on NM. Rat HSC cultured for 1 day on plastic plates (PP) were used as quiescent HSC, while cells cultured for 1 week on PP were considered to be activated HSC. Quiescent or activated HSC were subsequently plated on PP or NM and cultured for an additional 4 days at which time their gene expression, stress fiber development, and growth factor production were determined. For long-term culture, HSC were grown on NM for 20 days and the cells then replated on PP and cultured for another 10 days. Expression of marker genes for HSC activation, stress fiber development, and growth factor production were significantly lower in both quiescent and activated HSC cultured on NM than in those cultured on PP. After long-term culture on NM, activation marker gene expression and stress fiber development were still significantly lower in HSC than in PP, and HSC still retained the ability to activate when replated onto PP. HSC cultured on NM retained quiescent characteristics after both short- and long-term culture while activated HSC reverted toward a quiescent state when cultured on NM. Cultures of HSC grown on NM are a useful in vitro model to investigate the mechanisms of activation and deactivation.


Niclosamide: A career builder.
My contribution to honoring Professor Kinam Park celebrates and resonates with his scholarly career in drug delivery, his commitment to encouraging the next generation(s), and his efforts to keep us focused on clinically effective formulations. To do this I take as my example, niclosamide, a small molecule protonophore that, uniquely, can "target" all cell membranes, both plasma and organelle. As such, it acts upstream of many cell pathways and so has the potential to affect many of the essential events that a cell, and particularly a diseased cell or other entities like a virus, use to stay alive and prosper. Literature shows that it has so far been discovered to positively influence (at least): cancer, bacterial and viral infection, metabolic diseases such as Type II diabetes, NASH and NAFLD, artery constriction, endometriosis, neuropathic pain, rheumatoid arthritis, sclerodermatous graft-versus-host disease, systemic sclerosis, Parkinson's, and COPD. With such a fundamental action and broad-spectrum activity, I believe that studying niclosamide in all its manifestations, discovering if and to what extent it can contribute positively to disease control (and also where it can't), formulating it as effective therapeutics, and testing them in preclinical and clinical trials is a career builder for our next generation(s). The article is divided into two parts: Part I introduces niclosamide and other proton shunts mainly in cancer and viral infections and reviews an exponentially growing literature with some concepts and physicochemical properties that lead to its proton shunt mechanism. Part II focuses on repurposing by reformulation of niclosamide. I give two examples of "carrier-free formulations", -- one for cancer (as a prodrug therapeutic of niclosamide stearate for i.v. and other administration routes, exemplified by our recent work on Osteosarcoma in mice and canine patients), and the other as a niclosamide solution formulation (that could provide the basis for a preventative nasal spray and early treatment option for COVID19 and other respiratory virus infections). My goal is to excite and enthuse, encourage, and motivate all involved in the drug development and testing process in academia, institutes, and industry, to learn more about this interesting molecule and others like it. To enable such endeavors, I give many proposed ideas throughout the document, that have been stimulated and inspired by gaps in the literature, urgent needs in disease, and new studies arising from our own work. The hope is that, by reading through this document and studying the suggested topics and references, the drug delivery and development community will continue our lineage and benefit from our legacy to achieve niclosamide's potential as an effective contributor to the treatment and control of many diseases and conditions.


Forensic identification of resampling operators: A semi non-intrusive approach.
Recently, several new resampling operators have been proposed and successfully invalidate the existing resampling detectors. However, the reliability of such anti-forensic techniques is unaware and needs to be investigated. In this paper, we focus on the forensic identification of digital image resampling operators including the traditional type and the anti-forensic type which hides the trace of traditional resampling. Various resampling algorithms involving geometric distortion (GD)-based, dual-path-based and postprocessing-based are investigated. The identification is achieved in the manner of semi non-intrusive, supposing the resampling software could be accessed. Given an input pattern of monotone signal, polarity aberration of GD-based resampled signal's first derivative is analyzed theoretically and measured by effective feature metric. Dual-path-based and postprocessing-based resampling can also be identified by feeding proper test patterns. Experimental results on various parameter settings demonstrate the effectiveness of the proposed approach.


The important role of biochemical and functional studies in the diagnostics of peroxisomal disorders.
Peroxisomes are dynamic organelles that play an essential role in a variety of metabolic pathways. Peroxisomal dysfunction can lead to various biochemical abnormalities and result in abnormal metabolite levels, such as increased very long-chain fatty acid or reduced plasmalogen levels. The metabolite abnormalities in peroxisomal disorders are used in the diagnostics of these disorders. In this paper we discuss in detail the different diagnostic tests available for peroxisomal disorders and focus specifically on the important role of biochemical and functional studies in cultured skin fibroblasts in reaching the right diagnosis. Several examples are shown to underline the power of such studies.


Citrate-capped Mn-modified CdSe/CdS quantum dots as luminescent probes for levodopa detection in aqueous solution.
A novel kind of citrate capped Mn-modified CdSe/CdS quantum dots (QDs) was developed. The Mn-modified CdSe/CdS QDs had a narrow, symmetric emission and strong fluorescence with quantum yield over 41%. The interaction between the QDs and levodopa was investigated. The results showed that levodopa selectively quenched the fluorescence intensity of the QDs. Based on the fluorescence quenching of the synthesized QDs by levodopa, a simple, rapid and specific quantitative method for levodopa was proposed. The factors affecting the fluorescence detection for levodopa were studied. Under the optimum conditions, the quenched intensity of the fluorescence versus levodopa concentration from 1 to 100 μM gave a linear response with an excellent correlation coefficient of 0.9996, and the limit of detection (3σ/K) was 2 × 10(-7)M. The contents of levodopa in pharmaceutical tablets were determined by the proposed method and the results agreed with the claimed values.


COVID-19 induced telogen effluvium.
COVID-19 is a febrile, infectious illness that has previously been associated with telogen effluvium (TE). However, to date, no study has been conducted to determine the incidence of TE in those who have had COVID-19. To assess the frequency of TE in post-COVID-19 patients and the correlation between the development of TE and the severity of COVID-19, to understand whether emotional stress or medications are responsible for the development of TE. Totally 204 patients with a history of SARS-CoV-2 infection in the last 3 months were included in the study. The diagnosis of TE was made by history of excessive hair shedding, hair pull test, diffuse or bitemporal thinning, and absence of anisotrichosis in trichoscopy. Patients who did not have any TE cause other than COVID-19 and whose hair loss started after COVID-19 were considered as "COVID-19 associated TE (CATE)." We found TE in 75 (36.7%) cases and androgenetic alopecia (AGA) in 85 (41.7%) cases. CATE was present in 27.9% of cases and developed on average 53.76 (± 23.772) days after COVID-19 real-time reverse transcription polymerase chain reaction (RT-PCR) positivity. The proportion of patients with CATE was numerically higher in hospitalized patients compared to outpatients (31.7% vs. 24.3%; p = 0.238); and significantly higher in women compared to men (42.3% vs. 6.2%; p < 0.001), in patients with hypertension compared to those without hypertension (40.4% vs. 23.1%; p = 0.014), and in patients who had respiratory symptoms compared to those who had not (31.7% vs. 14.0%; p = 0.021). The patients with and without CATE were similar in terms of stress level and usage of COVID-19 medications. Patients with AGA had a higher rate of hospitalization (69.4% vs. 35.3%; p < 0.001) and a higher incidence of fever (69.4% vs. 54.6%; p = 0.033) during COVID-19, compared to those without. TE developed in approximately one-quarter of people who have had COVID-19, and our study is the first to detect it. The time to onset of CATE, which was 7-8 weeks after the SARS-CoV-2 RT-PCR positivity, was not much different from post-infectious TE. Patients with severe COVID-19 seem to be more prone to develop TE. The presence of AGA is associated with a more severe COVID-19. During the pandemic, clinicians should consider a previous SARS-CoV-2 infection in patients presenting with hair loss.


Survey of SARS-CoV-2 genetic diversity in two major Brazilian cities using a fast and affordable Sanger sequencing strategy.
Genetic variants of SARS-CoV-2 have been emerging and circulating in many places across the world. Rapid detection of these variants is essential since their dissemination can impact transmission rates, diagnostic procedures, disease severity, response to vaccines or patient management. Sanger sequencing has been used as the preferred approach for variant detection among circulating human immunodeficiency and measles virus genotypes. Using primers to amplify a fragment of the SARS-CoV-2 genome encoding part of the Spike protein, we showed that Sanger sequencing allowed us to rapidly detect the introduction and spread of three distinct SARS-CoV-2 variants in two major Brazilian cities. In both cities, after the predominance of variants closely related to the virus first identified in China, the emergence of the P.2 variant was quickly followed by the detection of the P1 variant, which became dominant in less than one month after it was first detected.


Further analysis of some symmetric and antisymmetric composite pulses for tackling pulse strength errors.
Composite pulses have found widespread use in both conventional Nuclear Magnetic Resonance experiments and in experimental quantum information processing to reduce the effects of systematic errors. Here we describe several families of time symmetric and antisymmetric fully compensating composite pulses, inspired by the previous Fn, Gn and BB1 families family developed by Wimperis. We describe families of composite 180° pulses (not gates) which exhibit unprecedented tolerance of pulse strength errors without unreasonable sensitivity to off-resonance errors, and related families with more exotic tailored responses. Next we address the problem of extending these methods to other rotation angles, and discuss numerical results for 90° pulses. Finally we demonstrate the performance of some 90° and 180° pulses in NMR experiments.


Very late drug-eluting stent thrombosis post exercise stress echocardiogram.
Stent thrombosis, although a rare event, has been the object of considerable interest because of its attendant morbidity and mortality and has come into focus with the advent of drug-eluting stents. We report a case of very late drug-eluting stent thrombosis occurring immediately after an exercise stress echocardiogram, in a patient who, 2 years earlier, had undergone primary percutaneous coronary intervention (PCI) for ST segment elevation myocardial infarction (STEMI). Similar cases reported in the literature and the possible mechanisms of stent thrombosis associated with exercise testing are reviewed.


Chromogranin, an integral membrane protein.
Chromogranin is the major soluble protein of the adrenal medulla chromaffin granule and is secreted upon nervous stimulation. Using antisera to pure chromogranin in immunoblotting procedures, we show that chromogranin is the major integral membrane protein as well. Extraction of chromaffin granule membranes with low salt, high salt, chelating agents, or calcium-containing solutions does not remove the chromogranin from the membranes. The membrane form of chromogranin can be purified on a C-18 semi-preparative column using high pressure liquid chromatography. Amino-terminal sequence data indicate that the membrane and soluble forms of chromogranin are identical or very similar.


[Rethinking clinical research in surgical oncology. From comic opera to quality control].
The evidence base for the effectiveness of surgical interventions is relatively poor and data from large, randomized prospective studies are rare with often a poor quality. Many efforts have been made to increase the number of high quality randomized trials in surgery and theoretical proposals have been put forward to improve the situation, but practical implementation of these proposals is seriously lacking. The consequences of this policy are not trivial; with very few patients included in surgical oncology trials, this represents wasted opportunity for advances in cancer treatment. In this review, we cover the difficulties inherent to clinical research in surgical oncology, such as quality control, equipoise, accrual, and funding and promote alternative designs to the randomized controlled trial. Although the classic randomized controlled trial has a valid but limited place in surgical oncology, other prospective designs need to be promoted as a new deal. This new deal not only implicates surgeons but also journal editors, tender jury, as well as regulatory bodies to cover legal gaps currently surrounding surgical innovation.