Immunotherapy and radiation.
Radiation therapy and immunotherapy are both well-established treatments for malignant disease. Radiotherapy has long been utilized for purposes of providing local tumor control, and the recent success with novel immunomodulatory agents has brought immunotherapy into the forefront of clinical practice for the treatment of many tumor types. Although radiotherapy has traditionally been thought to mediate tumor regression through direct cytotoxic effects, it is now known that radiation also alters the local tumor microenvironment with effects on both the local and systemic anti-tumor immune response. There is growing evidence that the rational integration of the immunomodulatory effects of radiotherapy with the expanding armamentarium of clinically approved immunotherapeutics can yield potent anti-tumor responses exceeding the benefit of either therapy alone. Here we summarize current approaches to the combination of immunotherapy with radiation therapy.


The Asian Voice in building equity in health for development - from the Asian Forum for Health Research, Manila, February 2000.
The Asian Forum for Health Research convened in Manila, the Philippines, in February 2000 to determine how best to create a new paradigm for health research in Asia. The forum was organized as an 'open university of research for equity in health development' to define the new paradigm and to identify methods for building a dynamic and collaborative architecture to more effectively link the nations and region of Asia with global stakeholders in health research. It was also to: determine Asian actions required to enhance leadership functions for innovative health research management; develop and disseminate tools and methodologies needed to accomplish essential tasks; establish collaborative networks within developing countries/regions to ensure efforts are not duplicated and international inputs are not monopolized; and use new information and communication technologies to integrate the process and contents of health research with equity in health development. Results of the forum's review of issues were presented and discussed at the International Conference on Health Research for Development, held in October 2000 in Bangkok, Thailand.


Charcot arthropathy secondary to amyloid neuropathy.
Neuropathic (Charcot) ankle joints developed in a 50-year-old patient with end-stage renal disease from primary, nonfamilial amyloidosis. Sensory neuropathy in the legs had been noted three years before the onset of uremia and had porgressed. Sural nerve, but not synovial biopsy specimen, showed amyloid in and around arteriolar walls by light and electron microscopy. Since Charcot joints are only rarely associated with amyloid neuropathy, it is possible that uremic neuritis, or prolonged survival by dialysis, contributed to progression of the neuropathy, allowing subsequent joint degeneration.


Performance of whole genome prediction for growth traits in a crossbred chicken population.
In the past decades, crossbreeding has been widely used to improve productivity in plant and animal husbandry. With the rapid implementation of genomic selection (GS) in these industries and a decrease in the cost of genotyping, genomic prediction (GP) with data from crossbred populations is an emerging research interest. Using a crossbred population derived from a cross between White Recessive Rock (WRR) and Xinghua (XH) chickens (n = 473), the predictive ability and selection differential of conventional best linear unbiased prediction (BLUP) and 3 GP methods (GBLUP, RKHS, and BayesB) were compared. All chickens were genotyped by a 60 K SNP chip. Twenty traits containing body weight (BW) at 1 to 90 d of age, breast muscle weight (BMW), leg muscle weight (LMW), wing weight (WW), and average daily gain (ADG) of different periods were analyzed. The accuracy of GP was higher than that of conventional BLUP for 18 out of 20 investigated traits. The average selection differential on BW selected with GP methods was greater than that from conventional BLUP, with a proportion selected varied between 5 and 30%. Overall, the GP methods outperformed conventional BLUP for both predictive ability and selection effect in the tested crossbred chicken population. Using genomic data from crossbred populations could potentially benefit the decision making for the purpose of marketing or breeding within crossbred population.


Asparaginase II of Saccharomyces cerevisiae: positive selection of two mutations that prevent enzyme synthesis.
A positive selection method, D-aspartic acid beta-hydroxamate resistance, was used to isolate Saccharomyces cerevisiae strains lacking the ability to synthesize asparaginase II. Of 100 such mutant strains, 93 exhibited mutations which were allelic with asp3, a previously characterized mutation. The other seven strains carried a new mutation, asp6. The asp6 mutation segregated 2:2 in asp6 X wild-type crosses and assorted from the asp3 mutation in asp6 X asp3 crosses. All seven asp6 mutant isolates reverted at a relatively high frequency, whereas the asp3 mutant isolates did not revert under the same conditions. Various independent asp3 isolates were mated to give heteroallelic diploids, which when sporulated and spread on D-asparagine medium yielded no recombinant strains.


Antiferromagnetic coupling between rare earth ions and semiquinones in a series of 1:1 complexes.
We use the strategy of diamagnetic substitution for obtaining information on the crystal field effects in paramagnetic rare earth ions using the homologous series of compounds with the diamagnetic tropolonato ligand, Ln(Trp)(HBPz(3))(2), and the paramagnetic semiquinone ligand, Ln(DTBSQ)(HBPz(3))(2), (DTBSQ = 3,5-di-tert-butylsemiquinonato, Trp = tropolonate, HBPz(3)= hydrotrispyrazolylborate) for Ln = Sm(iii), Eu(iii), Gd(iii), Tb(iii), Dy(iii), Ho(iii), Er(iii) or Yb(iii). The X-ray crystal structure of a new form of tropolonate derivative is presented, which shows, as expected, a marked similarity with the structure of the semiquinonate derivative. The Ln(Trp)(HBPz(3))(2) derivatives were then used as a reference for the qualitative determination of crystal field effects in the exchange coupled semiquinone derivatives. Through magnetisation and susceptibility measurements this empirical diamagnetic substitution method evidenced for Er(iii), Tb(iii), Dy(iii) and Yb(iii) derivatives a dominating antiferromagnetic coupling. The increased antiferromagnetic contribution compared to other radical-rare earth metal complexes formed by nitronyl nitroxide ligands may be related to the increased donor strength of the semiquinone ligand.


Association between inter-pregnancy interval and risk of adverse birth outcomes in subsequent pregnancy: A retrospective study from Jordan.
Adverse birth outcomes, such as preterm birth and low birth weight (LBW), are leading causes of neonatal morbidity and mortality. In this study, we aimed to estimate the association between inter-pregnancy interval (IPI) and the risks of adverse birth outcomes in a subsequent pregnancy. We conducted a retrospective analysis involving 630 mothers who delivered a singleton live infant at a leading tertiary hospital in northern Jordan from March to August 2021. Outcome variables were preterm birth (<37 weeks of gestation) and LBW (<2.5 kg). Using multivariable logistic regression, the association between IPI and these two adverse birth outcomes was investigated. The rates of preterm birth and LBW were 12.4% and 16.8%, respectively. Compared with an optimal IPI (24-36 months), a short IPI (<24 months) was positively associated with preterm birth (aOR: 4.09; 95% CI: 1.48-6.55) and LBW (aOR: 3.58; 95% CI: 1.57-5.15). Infants conceived after a long IPI (≥ 60 months) had increased odds of preterm birth (aOR: 3.78; 95% CI: 1.12-5.78) and LBW (aOR: 2.65; 95% CI: 1.67-4.03). Preterm delivery was also significantly associated with the mother's age (aOR: 1.10; 95% CI: 1.04-1.17), history of multiple cesarean births (aOR: 2.67; 95% CI: 1.14-4.29), prolonged rupture of membranes (aOR: 2.46; 95% CI: 1.10-5.52), and perinatal death (aOR: 3.42; 95% CI: 1.10-5.49). A mother's history of prior LBW (aOR: 4.39; 95% CI: 1.08-6.80), hypertensive disorders (aOR: 1.95; 95% CI: 1.03-3.89), and multiple cesarean births (aOR: 4.35; 95% CI: 2.10-6.99) was associated with LBW. Both short and long IPIs were related to preterm delivery and LBW. Optimal birth spacing is recommended to improve birth outcomes and must be considered when designing effective family planning programs.


Elevated Tenascin-C Serum Levels in Patients With Axial Spondyloarthritis.
This study aimed to examine serum tenascin C (TNC) in different subsets of axial spondyloarthritis (axSpA) patients. Sixty-one patients fulfilling the Assessment of SpondyloArthritis international Society classification criteria for axSpA and 20 healthy subjects (HS) were included in study. Based on imaging, patients were classified as non-radiographic (n=16) and radiographic (n=45) axSpA. TNC serum levels were determined by ELISA. Disease-related factors including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and C-reactive protein (CRP) levels, were determined. TNC levels were elevated in axSpA patients [535.3 (457.7-677.2) ng/ml] compared to HS [432.1 (329.1-565.9) ng/ml, p=0.007]. Dividing axSpA into radiographic and non-radiographic subsets, the difference in TNC was observed between the radiographic subset and HS [535.3 (434.5-677.2) vs. 432.1 (329.1-565.9) ng/ml, p=0.022]. TNC levels did not correlate with disease activity measures (serum CRP or BASDAI). Nevertheless, the weak correlation of TNC levels with different disease stages (r=0.25, p=0.025) was found, with the highest levels in patients with syndesmophytes. TNC levels are elevated across various subsets of axSpA, and although not related to systemic disease activity, TNC levels might reflect chronic structural spinal changes in axSpA patients. However, its specific role in bone metabolism should be elucidated in further studies.


A novel assay in vitro of human islet amyloid polypeptide amyloidogenesis and effects of insulin secretory vesicle peptides on amyloid formation.
Human islet amyloid polypeptide (IAPP) is a 37-residue peptide that is co-secreted with insulin by the beta-cell and might be involved in the pathogenesis of non-insulin-dependent diabetes mellitus. We developed an improved assay in vitro based on the fluorescence of bound thioflavin T to study factors affecting amyloidogenesis. Monomeric IAPP formed amyloid fibrils, as detected by increased fluorescence and by electron microscopy. Fluorimetric analysis revealed that the initial rate of amyloid formation was: (1) proportional to the peptide monomer concentration, (2) maximal at pH 9.5, (3) maximal at 200 mMKCl, and (4) proportional to temperature from 4 to 37 degreesC. We found that 5-fold and 10-fold molar excesses of proinsulin inhibited fibril formation by 39% and 59% respectively. Insulin was somewhat more potent with 5-fold and 10-fold molar excesses inhibiting fibril formation by 69% and 73% respectively, whereas C-peptide had no effect at these concentrations. Thus at physiological ratios of IAPP to insulin, insulin and proinsulin, but not C-peptide, can retard amyloidogenesis. Because insulin resistance or hyperglycaemia increase the IAPP-to-insulin ratio, increased intracellular IAPP compared with insulin expression in genetically predisposed individuals might contribute to intracellular amyloid formation, beta-cell death and the genesis of non-insulin-dependent diabetes mellitus.


Discrimination of Corynebacterium glutamicum, Brevibacterium flavum and Brevibacterium lactofermentum by restriction pattern analysis of DNA adjacent to the hom gene.
Different strains of Corynebacterium glutamicum, Brevibacterium flavum, and Brevibacterium lactofermentum were analysed for restriction fragment length polymorphism using the homoserine dehydrogenase gene (hom) as a probe. The hybridization patterns obtained PvuII- or Asp700-restriction of chromosomal DNA were specific and distinguishable for each of the three species and identical for the different strains of each species. Thus, the method employed allows rapid distinction of Corynebacterium glutamicum, Brevibacterium flavum, and Brevibacterium lactofermentum. The former species could also be discriminated from the latter two by its resistance to 0.5 g/l of the methionine analog ethionine.


[The effect of long-term administration of metipranolol on passive diastolic properties of the hypertrophic ventricle].
In the course of adaptation of the rabbit heart to volume load passive diastolic properties of the hypertrophic ventricle and myocardium were changing significantly. On day 30 following perforation of the aortic valve stiffness of the ventricle was reduced, yet normalized ventricular stiffness and myocardial stiffness were increased. These changes were prevented by beta adrenergic blockade during development of adaptation of the heart to volume load. Although ventricular stiffness was reduced, normalized ventricular stiffness and myocardial stiffness remained at the level of control values. The demonstrated effect of beta adrenergic blockade on passive diastolic properties of the ventricle and myocardium may be of value in preventing heart failure due to chronic hemodynamic load. (Tab.3,Ref.15.).


The effects of occupational noise on blood pressure and heart rate of workers in an automotive parts industry.
One of the most important impacts of industrial noise is physiological and psychological effects. The increases in workers' blood pressure and heart rate were detected during and after exposure to high levels of noise. The objectives of this research were to determine whether the noise exposures have any effects on blood pressure and heart rate of workers in the automotive parts industry. This case study was done in 2011 at different units of an automotive parts manufacturing in Tehran. Sound pressure level was measured at different units of the factory with a calibrated instrument. Demographic features of workers were gathered with an appropriate questionnaire. Heart rate and blood pressure were measured twice in a day in the start time of work day (before exposure to noise) and middle shift hours (during exposure to noise) in the occupational physician office. For analyzing data, chi-square, independent sample t-test, paired t-test, and analysis of covariance (ANCOVA) were used. P < 0.050 was considered statistically significant. The average age of workers in the case and control groups was 35.71 ± 8.10 and 33.40 ± 10.41 years, respectively. There was no difference between the average age of case and control groups (P = 0.436). The results of ANCOVA revealed the significant differences between the mean changes of heart rate F (1, 37) = 26.68, P < 0.001, systolic blood pressure F (1, 37) = 21.70, P < 0.001, and diastolic blood pressure F (1, 37) = 26.20, P < 0.001 of workers in the case and control groups. Exposure to industrial noise may increase the heart rate of workers. Although rises in heart rate, systolic, and diastolic blood pressure of workers in the case group were observed after exposure to noise, the values of heart rate, systolic, and diastolic blood pressure were in the normal range. Further experimental investigations are needed to determine the relationships between these variables.


The redox status of malaria-infected erythrocytes: an overview with an emphasis on unresolved problems.
The various mechanisms involved in the redox defence of normal erythrocytes are adequately known. They are herein briefly reviewed, outlining the principal enzymes and metabolic pathways, such as superoxide dismutase, catalase, glutathione peroxidase and reductase, the hexose monophosphate shunt (HMS) and glutathione synthesis and turnover. The intraerythrocytic malaria parasite is imposing an oxidative stress on its host cell. Malaria infected cells produce O2-, H2O2, enhance lipide peroxidation and activate host cell HMS. This stress is produced during the digestion of host cell hemoglobin by the parasite. Hence, both parasite and host cell must be able to confront this stress. The antioxidant defence systems of the parasite and the response of those systems in the infected host cell are reviewed, underscoring unresolved problems. Nothing is virtually known on the parasite's glutathione metabolism, and on possible interactions between host cell and parasite antioxidant defence systems. The postulate that 1. host cell activated HMS in conjunction with purine salvage can provide purine nucleotides to the parasite, and 2. that glutathione transferase can participate in parasite resistance to antimalarial drugs, are also discussed.


Photoallergic contact sensitization to 6-methylcoumarin in poikiloderma of Civatte.
A 49-year-old woman presented with asymptomatic progressive erythema, hyperpigmentation, atrophy, and telangiectasia on her neck. The clinical appearance and histopathology of the skin lesion was consistent with poikiloderma of Civatte. Photopatch-testing with our standard photoallergens yielded a positive reaction to 6-methylcoumarin, which was found in the patient's perfume. This report describes the first case in which photoallergic contact sensitization to 6-methylcoumarin may play an important role in the pathogenesis of poikiloderma of Civatte.


Effect of different cycling-off criteria and positive end-expiratory pressure during pressure support ventilation in patients with chronic obstructive pulmonary disease.
During pressure support ventilation, ventilator inspiration ends when inspiratory flow drops to a given percentage of the peak inspiratory flow cycling-off criteria. This study evaluated the effect of two different cycling-off criteria on breathing pattern, respiratory effort, and gas exchange in patients with chronic obstructive pulmonary disease. Clinical study. Thirteen mechanically ventilated patients with acute exacerbation of chronic obstructive pulmonary disease primarily due to pneumonia (PaO2/FIO2 291 +/- 114 mm Hg, PaCO2 53 +/- 19 mm Hg). Two cycling-off criteria (5% and 40% of the peak inspiratory flow) at two levels of pressure support (5 and 15 cm H2O) with and without the application of an external positive end-expiratory pressure (6 and 0 cm H2O) were applied. Measurement Patient-ventilator time delay of cycling-off was computed as the difference between the end of inspiratory flow and the lowest value of inspiratory esophageal pressure. Inspiratory effort was estimated by computing the work of breathing, the pressure time product partitioned into the total pressure time product, and the pressure time product due to the dynamic intrinsic positive end-expiratory pressure. At 5 and 15 cm H2O of pressure support ventilation, the cycling-off criteria 40% significantly reduced the patient-ventilator time delay of cycling-off from 0.40 +/- 0.20 secs to 0.29 +/- 0.16 secs and from 0.93 +/- 0.50 secs to 0.52 +/- 0.25 secs, respectively; the dynamic intrinsic positive end-expiratory pressure from 3.9 +/- 1.8 cm H2O to 3.1 +/- 2.1 cm H2O and from 2.4 +/- 2.0 cm H2O to 1.7 +/- 1.4 cm H2O, respectively; and the pressure time product due to the dynamic intrinsic positive end-expiratory pressure. At 5 cm H2O of pressure support, the cycling-off criteria 40% significantly reduced the tidal volume and the inspiratory effort. The modification of cycling-off criteria did not affect the gas exchange. The modification of cycling-off criteria may have a beneficial effect on reducing the dynamic hyperinflation and inspiratory effort in chronic obstructive pulmonary disease patients, especially at low levels of pressure support.


Investigating an outbreak of measles in Margibi County, Liberia, October 2015.
The emergence and re-emergence of infectious diseases highlights the need to have well-trained field epidemiologists who will be at the forefront in the fight against these diseases, especially during an outbreak. Training for outbreak investigation is most effective when participants can develop their competencies in a practical exercise. To that end, this case study was based on a measles outbreak investigation conducted in Liberia during October 2015 by Liberia Frontline Field Epidemiology Training Program (FETP) residents, simulating steps to perform outbreak investigation in a real-life situation as a field epidemiologist. This case study is ideally suited to reinforce principles and skills already covered in a classroom lecture or in background reading by providing a practical training beyond the scope of theoretical learning. It is primarily intended for training novice public health practitioners who should be able to complete the exercises in approximately 3 hours.


Evaluation of the Blunt Pancreatic Injury, a Long-Term Tertiary Care Center Study: An Original Research.
Pancreatic trauma is uncommon and challenging to diagnose. Contrarily, severe injuries to the kidney, spleen, and liver are frequent and typically easy to detect with imaging methods. Pancreas injuries can cause a significant amount of morbidity and mortality. Reviewing the institution's experience with this rather infrequent injury was the goal of this study. The patients' records were collected from the data records at the tertiary care center for patients who had pancreatic damage and were followed up for a year. The American Association for the Surgery of Trauma pancreatic damage grade scores were assigned to each patient using the radiologic and surgical findings. Clinical examination and CT results were predominantly used to make the diagnosis in patients who underwent non-operative treatment. The data are presented as descriptive statistics. Only 2.2% of the total cases that presented to the trauma center were finalized as pancreatic injuries. Trauma to the abdomen was seen in nearly half the cases brought. Most of the subjects in pancreatic injuries were in grade 3. Mortality was noted maximum for the grade 3 and 4 cases. While high-grade pancreatic injury almost always requires an operational intervention, low-grade pancreatic injury with an intact main pancreatic duct may be effectively handled non-operatively. When possible, distal pancreatectomy with spleen preservation is the ideal procedure for distal pancreatic trans-action. A patient who is hemodynamically stable with complex pancreaticoduodenal damage, which is related to a high death rate, should undergo Whipple resection.


Comparability of FDG PET studies in probable Alzheimer's disease.
Results of studies with positron emission tomography (PET) of 18F-2-fluoro-2-deoxy-D-glucose (FDG) in patients with probable Alzheimer's disease (AD) were compared among three European centers with different PET scanners (in-plane resolution ranging between 6.75 mm and 9.2 mm). A ratio of glucose metabolism in the most typically affected regions over the least typically affected regions was calculated to quantitatively analyze the characteristic pattern of AD. Diagnostic accuracy of this composite ratio was high (95.8%) and was superior to that of most ratios derived from single regions. Correspondingly, there was a consistent, highly significant difference between patients (mean ratio 0.77 +/- 0.11) and normals (mean 0.99 +/- 0.04) without significant differences among laboratories. Possible small effects of rate constant variation and region size were analyzed by computer simulation. The results demonstrate that a common investigation protocol may yield FDG PET data in different laboratories that are closely comparable in spite of differences between scanners and imaging equipment.


Targeted Cancer Immunotherapy: Nanoformulation Engineering and Clinical Translation.
With the rapid growth of advanced nanoengineering strategies, there are great implications for therapeutic immunostimulators formulated in nanomaterials to combat cancer. It is crucial to direct immunostimulators to the right tissue and specific immune cells at the right time, thereby orchestrating the desired, potent, and durable immune response against cancer. The flexibility of nanoformulations in size, topology, softness, and multifunctionality allows precise regulation of nano-immunological activities for enhanced therapeutic effect. To grasp the modulation of immune response, research efforts are needed to understand the interactions of immune cells at lymph organs and tumor tissues, where the nanoformulations guide the immunostimulators to function on tissue specific subsets of immune cells. In this review, recent advanced nanoformulations targeting specific subset of immune cells, such as dendritic cells (DCs), T cells, monocytes, macrophages, and natural killer (NK) cells are summarized and discussed, and clinical development of nano-paradigms for targeted cancer immunotherapy is highlighted. Here the focus is on the targeting nanoformulations that can passively or actively target certain immune cells by overcoming the physiobiological barriers, instead of directly injecting into tissues. The opportunities and remaining obstacles for the clinical translation of immune cell targeting nanoformulations in cancer therapy are also discussed.


Single nucleotide polymorphism of bone morphogenetic protein 4 gene: A risk factor of non-syndromic cleft lip with or without palate.
The bone morphogenetic protein (BMP) signalling pathway is crucial in a number of developmental processes and is critical in the formation of variety of craniofacial elements including cranial neural crest, facial primordium, tooth, lip and palate. It is an important mediator in regulation of lip and palate fusion, cartilage and bone formation. To study the role of mutation of BMP4 genes in the aetiology of non-syndromic cleft lip with or without palate (NSCL ± P) and identify it directly from human analyses. A case-control study was done to evaluate whether BMP4T538C polymorphism, resulting in an amino acid change of Val=Ala (V152A) in the polypeptide, is associated with NSCL ± P in an Indian paediatric population. Genotypes of 100 patients with NSCL ± P and 100 controls (in whom absence of CL ± P was confirmed in three generations) were detected using a polymerase chain reaction-restriction fragment length polymorphism strategy. Logistic regression was performed to evaluate allele and genotype association with NSCLP. Results showed significant association between homozygous CC genotype with CL ± P (odds ratio [OR]-5.59 and 95% confidence interval [CI] = 2.85-10.99). The 538C allele carriers showed an increased risk of NSCL ± P as compared with 538 T allele (OR - 4.2% CI = 2.75-6.41). This study suggests an association between SNP of BMP4 gene among carriers of the C allele and increased risk for NSCLP in an Indian Population. Further studies on this aspect can scale large heights in preventive strategies for NSCLP that may soon become a reality.


Wandering in both mind and body: individual differences in mind wandering and inattention predict fidgeting.
Anecdotal reports suggest that during periods of inattention or mind wandering, people tend to experience increased fidgeting. In four studies, we examined whether individual differences in the tendency to be inattentive and to mind wander in everyday life are related to the tendency to make spontaneous and involuntary movements (i.e., to fidget). To do so, we developed self-report measures of spontaneous and deliberate mind wandering, as well as a self-report scale to index fidgeting. In addition, we used several existing self-report measures of inattentiveness, attentional control, and memory failures. Across our studies, a series of multiple regression analyses indicated that fidgeting was uniquely predicted by inattentiveness and spontaneous mind wandering but not by other related factors, including deliberate mind wandering, attentional control, and memory failures. As a result, we suggest that only spontaneously wandering thoughts are related to a wandering body.


Effects of cytostatic drugs on the transmembrane potential and surface charge of cultured cells.
The transmembrane potential, the surface charge and the cell count were measured on cells cultured in vitro under the influence of various cytostatic substances. Lower concentrations of the agents induced an increase in membrane polarization. On the other hand membrane depolarization grew with both increasing exposure to cytostatic substances and rising content of the latter in the medium. The influence of higher doses was accompanied by morphological cell damage as well as a decrease in the surface charge of cells after a lengthy incubation time. Immediately after addition of chemotherapeutic substances to the cell cultures a damped oscillation of the TMP was observed. This clearly supports that the TMP is a rapidly reacting and very sensitive indicator for a great number of cell functions and an additional parameter in pretherapeutic sensitivity tests.


Myocardial vagal stimulation impairs lower esophageal sphincter function.
Coronary artery disease and gastroesophageal reflux disease frequently coexist, but a direct pathophysiologic link has not been established. This study examines the effect of myocardial vagal receptor stimulation on lower esophageal sphincter (LES) tone in eight adult mongrel dogs, each acting as its own control. Pharmacologic stimulation was carried out by the application of 1 cm gauze patches soaked in nicotine (200 micrograms/ml) to the epicardium. Epicardial vagal receptors were stimulated mechanically by digital friction. Pharmacologic stimulation produced a rapid fall in LES tone from a mean (SEM) of 12.6 (1.5) to 8.6 (0.9) sphinctometer units (p = 0.007). Mechanical stimulation also produced a rapid fall from 12.0 (1.5) sphinctometer units to 6.8 (0.7) (p = 0.007). Both were associated with a drop in mean arterial blood pressure and heart rate. Sham patches soaked in sterile water produced no effects. These data suggest a direct vagal reflex linking the myocardium and the LES that may explain the high incidence of gastroesophageal reflux in patients with heart disease.


Physiotherapeutic Interventions for Individuals Suffering From Plantar Fasciitis: A Systematic Review.
The foot and the lower leg comprise the ankle joint complex. The foot is crucial for the maintenance of posture. Frequently, overuse or repeated microtrauma to the fascia causes plantar fasciitis. This review aims to suggest the efficacy of various plantar fasciitis (PF) interventions based on modifications in clinical results. This review included studies from 2019 to March 2023 identified through a systematic literature search. The measures used to predict improvement in pain, discomfort, and foot function symptoms included the Visual Analog scale, Numerical Pain Rating Scale, Pressure Point Threshold by algometer, Weight-Bearing Lunge Test by inch tape, and range of motion. The review included 20 studies that fulfilled the inclusion criteria. Therapeutic interventions included insoles, foot orthosis, foam roller stretching, manual stretching, muscle strengthening, intrinsic muscle activities, extracorporeal shock wave lithotripsy, dry needling, laser, ultrasound, and others, which resulted in pain reduction, improved foot function, and ease of everyday routine. All therapeutic strategies used impacts resulting from minimal to maximal recovery. Various advanced approaches are more effective than conventional physical therapy. In conclusion, conservative therapeutic strategies with manual techniques, orthoses, and alternative intervention strategies can be combined to effectively relieve pain and improve function and overall results. Further high-quality studies are essential to learn more about the ideal dose, treatment approaches, and long-term impacts of these therapies.


Hand hygiene compliance among healthcare workers before and during the COVID-19 pandemic.
Healthcare workers' (HCWs) adherence to hand hygiene is vital in combatting COVID-19 in hospitals. We aimed to investigate HCWs hand hygiene compliance before and during the COVID-19 pandemic and hypothesised that hand hygiene compliance would increase during the pandemic. We conducted a prospective observational study in three medical departments at the Regional Hospital of West Jutland, Denmark from April 2019 to August 2020. A total of 150 HCWs participated before the COVID-19 pandemic and 136 during the pandemic. Hand hygiene observations were assessed using an automated hand hygiene monitoring system. Students unpaired t-test was used to assess differences in hand hygiene compliance rates in each department. Comparison analyses showed, that hand hygiene compliance in department A and B was significantly higher before the COVID-19 pandemic than during the pandemic; a 7% difference in department A and a 5% difference in department B. For department C, the total hand hygiene compliance was unchanged during the pandemic compared to before. The COVID-19 pandemic did not raise hand hygiene compliance. Further studies are needed to verify these findings and further identify barriers to hand hygiene compliance among HCWs.


Fast Dynamics of Water Droplets Freezing from the Outside In.
A drop of water that freezes from the outside in presents an intriguing problem: the expansion of water upon freezing is incompatible with the self-confinement by a rigid ice shell. Using high-speed imaging we show that this conundrum is resolved through an intermittent fracturing of the brittle ice shell and cavitation in the enclosed liquid, culminating in an explosion of the partially frozen droplet. We propose a basic model to elucidate the interplay between a steady buildup of stresses and their fast release. The model reveals that for millimetric droplets the fragment velocities upon explosion are independent of the droplet size and only depend on material properties (such as the tensile stress of the ice and the bulk modulus of water). For small (submillimetric) droplets, on the other hand, surface tension starts to play a role. In this regime we predict that water droplets with radii below 50 μm are unlikely to explode at all. We expect our findings to be relevant in the modeling of freezing cloud and rain droplets.


Left Ventricular Thrombus Formation After ST-Segment-Elevation Myocardial Infarction: Insights From a Cardiac Magnetic Resonance Multicenter Study.
Data on left ventricular (LV) thrombus formation after primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction (STEMI) are scarce. The aims of this study were to assess the (1) incidence of LV thrombi using cardiac magnetic resonance in a multicenter cohort of STEMI patients and (2) prognostic relevance of LV thrombi at 1-year follow-up. In total, 738 STEMI patients reperfused by primary angioplasty were enrolled in 8 centers. Cardiac magnetic resonance was completed within 1 week after infarction. Central core laboratory-masked analyses for the presence of LV thrombi were performed. The primary clinical end point was the occurrence of major adverse cardiac events within 1 year. LV thrombi were detected in 26 patients (3.5%) in the overall cohort and in 7.1% in anterior STEMI patients. The presence of thrombi was associated with larger infarcts (P<0.001), less myocardial salvage (P<0.01), impaired LV ejection fraction (P<0.001), and more pronounced late microvascular obstruction (P=0.002). The presence of thrombi was independently associated with the incidence of major adverse cardiac events at 12 months (hazard ratio, 2.73; 95% confidence interval, 1.11-6.73; P=0.03). In this multicenter cohort of patients with STEMI, thrombus prevalence assessed by cardiac magnetic resonance was 3.5% and associated with decreased myocardial salvage, larger infarcts, and more pronounced reperfusion injury. Importantly, LV thrombus was independently associated with major adverse cardiac events at 1-year follow-up. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00712101.


Association between two polymorphisms of histamine-metabolising enzymes and the severity of allergic rhinitis in a group of Mexican children.
It has been suggested that polymorphisms of histamine metabolising enzymes can be a risk factor for developing histamine-involving diseases. The aim of the present study is to research the possible association between two functional single nucleotide polymorphisms (SNPs): C314T in the Histamine-N-Methyl Transferase gene and C2029G in the Diamine Oxidase gene, with the severity of allergic rhinitis and the number of allergic diseases, in a group of allergic Mexican children. We studied 154 unrelated allergic children. SNPs were analysed by RT-PCR. The total serum IgE was measured by chemiluminescence and the serum histamine by ELISA. We used logistic regression analysis to determine OR. Patients carrying the mutant allele for any SNP had more risk to develop higher rhinitis severity or a bigger number of allergic diseases. Haplotype analysis revealed that this effect is synergistic. In patients carrying one or two mutant alleles, serum histamine levels were higher than those of patients carrying only wild alleles. Serum IgE levels were not associated with the presence of mutant alleles. The presence of these SNPs in patients with allergic rhinitis can lead to higher serum histamine, therefore to a higher risk of developing more severe symptoms or more associated allergic diseases, even if the serum IgE remains low.


Echocardiography algorithms to assess high left atrial pressure and grade diastolic function in preterm infants.
Relaxation, restoring forces, myocardial stiffness and atrial function determine left ventricular (LV) diastolic function. This study aims to provide a comprehensive assessment of diastolic function in preterm infants using conventional echocardiography and speckle tracking imaging and determine the diagnostic accuracy of various algorithms to detect high left atrial pressure (LAP). Preterm infants received an echocardiogram 1 week after birth and diastolic reference values were derived from the outer percentiles of stable preterm infants. Impaired relaxation, LV stiffness and high LAP were defined by using algorithms where at least half of the parameters were outside the normal range. Diastolic function was graded using the 2016 American Society of Echocardiography algorithm and expanded with the EA ratio and left atrial strain. The diagnostic accuracy of various algorithms to detect high LAP was determined with sensitivity analysis. We studied 146 infants (59 stable) with a mean of 27(1) weeks gestation. Impaired relaxation, LV stiffness and high LAP were found in 8%, 7%, and 14% of infants. The patent ductus arteriosus was a contributing factor to high LAP and LV stiffness, not impaired relaxation. Diagnostic accuracy improved from 90% to 96% and sensitivity from 40% to 90% by adding left atrial strain to the 2016 algorithm. Various grades of diastolic dysfunction could be appreciated in preterm infants using a multi-parameter approach. Adding left atrial strain improved sensitivity to detect infants with high LAP.


Speech and voice analysis after near-total laryngectomy and tracheoesophageal puncture with implantation of Provox 2 prosthesis.
Vocal characteristics were compared in two groups of patients who were operated on due to laryngeal cancer. One group was composed of patients after near-total laryngectomy and the other after total laryngectomy followed by tracheoesophageal puncture with implantation of Provox 2 prosthesis. Acoustic analysis was carried out using the EZ Voice Plus program and included the following parameters: fundamental frequency, jitter, shimmer, harmonic to noise ratio, range of fundamental frequency, maximal phonation time and intensity.


Powerline interference reduction in ECG signals using empirical wavelet transform and adaptive filtering.
Separating an information-bearing signal from the background noise is a general problem in signal processing. In a clinical environment during acquisition of an electrocardiogram (ECG) signal, The ECG signal is corrupted by various noise sources such as powerline interference (PLI), baseline wander and muscle artifacts. This paper presents novel methods for reduction of powerline interference in ECG signals using empirical wavelet transform (EWT) and adaptive filtering. The proposed methods are compared with the empirical mode decomposition (EMD) based PLI cancellation methods. A total of six methods for PLI reduction based on EMD and EWT are analysed and their results are presented in this paper. The EWT-based de-noising methods have less computational complexity and are more efficient as compared with the EMD-based de-noising methods.


Some biological and physico-chemical properties of porcine circovirus.
Some important biological and physico-chemical characteristics of porcine circovirus are reported. These include a study on the host distribution in nature, levels of colostrum-derived antibodies in piglets from sero-positive sows and the susceptibility of a range of cell cultures to infection with this virus. The results of haemagglutination studies, resistance to pH 3, chloroform and heat are also reported as are comparative buoyant densities and sedimentation coefficients of porcine circovirus and chicken anaemia virus.


Transforming growth factor (TGF beta) decreases the proliferation of human bone marrow fibroblasts by inhibiting the platelet-derived growth factor (PDGF) binding.
Human bone marrow fibroblasts were cultivated and characterized by immunofluorescent staining and electron microscopy. Their interactions with PDGF and TGF beta were studied. While a positive intracellular antifibronectin staining was observed, the cultured cells were not labeled with specific antibodies toward factor VIII von Willebrand factor (F VIII/vWF), desmin, and macrophage antigen. Moreover, electron microscopy excluded the presence of endothelial cells by the absence of Weibel-Palade bodies. The binding of pure human PDGF to the cultured bone marrow fibroblasts was investigated. Addition of an excess of unlabeled PDGF decreased the binding to 75 and 80%, which means that the nonspecific binding represented 20-25% of total binding, whereas epidermal growth factor (EGF) had no effect. Two classes of sites were detected by Scatchard analysis with respectively 21,000 and 37,000 sites per cell, with a KD of 0.3 x 10(-10) M and KD of 0.5 x 10(-9) M. The stimulation of DNA synthesis by PDGF was quantified by [3H]thymidine incorporation. When PDGF was added alone at a concentration of 15 ng/ml, it induced a maximal DNA synthesis of 400%, which increased up to 900%, in the presence of platelet-poor plasma (PPP). On the other hand, PDGF-induced fibroblast proliferation was inhibited in a dose-dependent manner by TGF beta. This inhibition was related to a significantly decreased binding of 125I-labeled PDGF observed in the presence of TGF beta. Our results suggested that PDGF and TGF beta could modulate the growth of bone marrow fibroblasts.


EUS-guided transcolonic drainage and necrosectomy in walled-off necrosis: a retrospective, single-center case series.
Background and study aims Transgastric endoscopic ultrasound (EUS)-guided drainage and, if needed, necrosectomy is the preferred treatment in patients with pancreatic walled-off necrosis. EUS-guided transcolonic or transrectal drainage and necrosectomy may serve as a minimally invasive alternative in cases in which transgastric or percutaneous drainage is either impossible or fails to secure sufficient drainage. In this paper, we retrospectively evaluated the feasibility, safety, and efficacy of the treatment. We included nine patients and found a technical success rate of 100%, clinical success in 89%, and one adverse event (11%). Transrectal/transcolonic endoscopic necrosectomy was needed in seven patients (78%).


Feasibility of a large area x-ray sensitive vidicon for medical fluoroscopy: resolution and lag factors.
A large area x-ray-sensitive vidicon utilizing amorphous selenium (a-Se) is being investigated as an alternative to the x-ray image intensifier and television camera combination (XRII/TV) for medical fluoroscopy. The x-ray vidicon is, to a first approximation, a scaled up version of the 1" (2.54 cm) light-sensitive vidicon. The modulation transfer function (MTF) of an x-ray vidicon is mainly determined by the number of lines used, the beam spot profile, and the electronic bandwidth. The x-ray vidicon is expected to have roughly the same MTF as the 1" vidicon from a XRII/TV system referenced to the x-ray input and as such will be superior to the MTF of the complete XRII/TV system especially in high resolution applications such as cardiac cine. Beam discharge lag is expected to be approximately the same as in the 1" vidicon since they have comparable photoconductor layer capacitance. Photoconductive lag is also expected to be low since a-Se is known to have a low trap density.


Generalized linear mixed models for meta-analysis.
We examine two strategies for meta-analysis of a series of 2 x 2 tables with the odds ratio modelled as a linear combination of study level covariates and random effects representing between-study variation. Penalized quasi-likelihood (PQL), an approximate inference technique for generalized linear mixed models, and a linear model fitted by weighted least squares to the observed log-odds ratios are used to estimate regression coefficients and dispersion parameters. Simulation results demonstrate that both methods perform adequate approximate inference under many conditions, but that neither method works well in the presence of highly sparse data. Under certain conditions with small cell frequencies the PQL method provides better inference.


Calcium-dependent protein kinase 29 modulates PIN-FORMED polarity and Arabidopsis development via its own phosphorylation code.
PIN-FORMED (PIN)-mediated polar auxin transport (PAT) is involved in key developmental processes in plants. Various internal and external cues influence plant development via the modulation of intracellular PIN polarity and, thus, the direction of PAT, but the mechanisms underlying these processes remain largely unknown. PIN proteins harbor a hydrophilic loop (HL) that has important regulatory functions; here, we used the HL as bait in protein pulldown screening for modulators of intracellular PIN trafficking in Arabidopsis thaliana. Calcium-dependent protein kinase 29 (CPK29), a Ca2+-dependent protein kinase, was identified and shown to phosphorylate specific target residues on the PIN-HL that were not phosphorylated by other kinases. Furthermore, loss of CPK29 or mutations of the phospho-target residues in PIN-HLs significantly compromised intracellular PIN trafficking and polarity, causing defects in PIN-mediated auxin redistribution and biological processes such as lateral root formation, root twisting, hypocotyl gravitropism, phyllotaxis, and reproductive development. These findings indicate that CPK29 directly interprets Ca2+ signals from internal and external triggers, resulting in the modulation of PIN trafficking and auxin responses.


Metabolite characterization of powdered fruits and leaves from Adansonia digitata L. (baobab): A multi-methodological approach.
The metabolite profiling of extracts from Adansonia digitata L. (baobab) fruit pulp and leaf, and the quantification of their major components, was conducted by means of reverse-phase, high-performance liquid chromatography with photodiode array detection, coupled to electrospray ion-trap mass spectrometry (RP-HPLC-PDA-ESI-MS/MS) and high field nuclear magnetic resonance (NMR) spectroscopy. Water-soluble metabolites from chemical classes including sugars, amino acids, organic acids, and phenolic compounds, were identified, in addition to metabolites soluble in organic solvents such as triacylglycerides, sterols, and fatty acids, and most of these were quantified. The profiling of the primary and secondary metabolites of baobab fruit and leaves addresses the limited knowledge of the chemical composition of baobab, and helps support and explain the growing evidence on its nutritional and biological properties, and provide suggestions about the possible uses of baobab fruit and leaves by food, pharmaceutical and cosmetic industries.


Unusual Case of Gallbladder Adenocarcinoma Metastasis to the Abdominal Wall 11 Years Later: Synchronous Presentation with Two Malignant Colon Tumors, Coincidence or Not?
Abdominal wall masses are a common finding in clinical practice. A high percentage of these masses are malignant. We present the case of a patient operated for a gallbladder adenocarcinoma, who consulted eleven years later for a malignant mass of the abdominal wall in synchrony with two adenocarcinomas of the left colon and sigmoid. Case Report. A 75-year-old male underwent a laparoscopic cholecystectomy with an incidental diagnosis of adenocarcinoma in situ (TisN0M0 according to AJCC 8th edition). The operative report mentioned that the removal of the gallbladder was difficult due to the inflammatory process, and the gallbladder was accidentally opened during the operation. It was not clear from the operative report whether an extraction bag was utilized to remove the specimen, but the histopathological study confirmed an open gallbladder. He presented 11 years later with an asymptomatic heterogeneous complex cystic mass involving the anterior rectus abdominis muscle. Colonoscopy showed synchronous tumors in the descending and sigmoid colon with pathology confirming adenocarcinoma. The patient underwent an elective laparotomy with resection of the anterior abdominal wall mass, left hemicolectomy, and sigmoidectomy. The histopathological results of the abdominal mass (CK7, CK20, EMA, CEA positive) were described as metastasis of adenocarcinoma of biliary origin. Discussion. Port site recurrences are rare complications following laparoscopic surgery when malignancy is unsuspected. Possible factors related to local implantation include direct seeding of spilled bile or tumor cells into the wound or shedding of tumor cells due to pneumoperitoneum-induced loss of the peritoneal barrier at the trocar site. In the absence of distant metastasis, treatment should include wide port site excision with malignancy-free surgical margins. Abdominal wall metastasis from gallbladder carcinoma is rare, and its synchronous presentation with a malignant neoplasm of the colon is exceptional. This is the first report of a patient with abdominal wall metastasis from a gallbladder adenocarcinoma operated eleven years ago that debuted synchronously with two adenocarcinomas of the left colon and sigma.


Same modality nerve reconstruction for accessory nerve injuries.
The standard repair of a nerve gap under tension is to use a sensory autograft, such as the medial antebrachial cutaneous or the sural nerve. The practice of using sensory grafts to repair motor nerve defects is challenged by the discovery of preferential motor reinnervation and modality specific nerve regeneration. In this article, two clinical cases are presented where accessory nerve injuries are repaired with either a motor nerve transfer (a branch of C7) or a motor autograft (obturator nerve), and excellent functional results are reported. These cases provide a stimulus to consider the use of motor nerve grafts or transfers in the repair of motor nerve deficits.


Awareness and ethical views regarding life support among doctors working in tertiary care facilities of Karachi, Pakistan.
To assess the knowledge of Life Support (LS) among doctors and to determine their ethical beliefs for the continuation or termination of Basic and Advanced Life Support services. This cross-sectional study was done from March to June 2009 that involved 110 doctors of three teaching Hospitals in Karachi (Jinnah Postgraduate Medical Centre, Aga Khan University and Ziauddin University hospitals). All the subjects were selected by random sampling and were then analysed on the basis of self-administered questionnaires. Out of the 110 doctors who took the survey, 109 (99%) had heard of Life Support. In the breakdown of doctors, 1 out of the 18 consultants (5.6%), 5 of 45 PGs (11%) and 2 out of 47 House Officers (4%) who took part in this study were unable to correctly identify the right definition of LS. Out of the total number (n = 110) of doctors, 94 (85%) said they would use Life Support in their patients and 41 (43%) of them thought life support was the only way the doctor can "do what he is supposed to do i.e. save a life", while the other reason for using LS was "Religiously, the right way". LS is still a highly sensitive subject that needs still more awareness in Karachi, Pakistan. It was surprising to find out that the knowledge of LS by residents, postgraduates and even consultants was not as high as expected. Making Basic Life Support as a part of the undergraduate course might help in clarifying the discrepancies present in the knowledge of Life Support.


The turnover of cyclic AMP in cultured fibroblasts.
The determination of the turnover of cAMP in WI-38 and VA13 cultured fibroblasts stimulated by prostaglandin E1 is reported. The method made use of data obtained from a process of continuously labeling the cellular adenine nucleotide pools by incubation with [3H]-adenine. The turnover of the cAMP was estimated from the delay in appearance of tritium label in the cAMP pool was compared to the cellular ATP. For WI-38 cells the half-life of cAMP when accumulation had reached a steady-state was 1.46 minutes; in the presence of 0.5 mM 1-methyl-3-isobutylxanthine (IBMX) the half-life was increased to 9.24 minutes. For VA13 transformed fibroblasts the half-life of cAMP determined by this method was 6.30 minutes. cAMP in these latter cells in the absence of hormone had a half-life of 3.01 minutes. This decrease supports the contention that the hormone has profound effects on phosphodiesterase as well as adenylate cyclase activities in these cells.


Childhood maltreatment and suicidality among women seeking mental health care: the mediating effect of borderline personality features, moderated by age.
Although childhood maltreatment is known to elevate women's risk for suicidal ideation and behavior, research concerning the mechanisms involved remains limited. While borderline personality disorder (BPD) has been implicated as mediating this association, such effects may differ depending on women's age. The present study examined borderline personality features as a dispositional mediator of the relationship between childhood maltreatment and suicidality, with the moderating effect of age, among help-seeking women. A sample of 151 women attending community mental health clinics completed measures of childhood maltreatment, BPD features, suicidality, and psychological distress. Regression analyses tested moderated mediation, controlling for psychological distress across each path. Results indicated a significant interaction between childhood maltreatment and age in predicting borderline personality features, and significant moderated mediation in predicting suicidality. Borderline personality features significantly mediated the association between maltreatment and suicidality among younger--but not among older--women, with the mediation effect becoming stronger as women were younger. The findings indicate borderline personality features as particularly salient among young women in accounting for the maltreatment-suicidality association. Thus, interventions addressing BPD may warrant consideration for young women with suicidal ideation and history of childhood adversity.


Prevalence of potentially traumatic events, depression, alcohol use, and social network supports among Chinese migrants: an epidemiological study in Guangzhou, China.
Addressing the health needs of Chinese migrants is a critical public health concern. Epidemiological studies are needed to establish the prevalence of potentially traumatic events (PTEs) and common mental disorders among Chinese migrants and identify protective community and social resources. Utilizing random household sampling, we are in the process of recruiting a representative sample of Chinese adults (N=1,000) in two districts home to a large number of internal migrants. Data are collected using face-to-face interviews and participant self-report methods. Chinese versions of the Life Events Checklist, Alcohol Use Disorders Identification Test, Patient Health Questionnaire and the Social Support Rating Scale measured exposure to PTEs, alcohol use disorder, depression, and social support networks. Preliminary results indicate a high proportion (68%) of the sample was exposed directly or indirectly to at least one PTE. The most commonly reported events were transportation accidents (43%), natural disasters (39%), and physical assault (26%). A total of 17% of the sample reported drinking consistent with having an alcohol use disorder. Moderate or severe depression was reported by 9% of the sample. The majority (75%) reported having three or more people to rely on for support, and 41% reported active participation in civic groups. Despite these strengths, only half the sample reported having trust in their community. Preliminary evidence from this population-level survey indicates high exposure to PTEs and a high potential burden of alcohol use disorders. The role of social networks will be explored as potentially useful for community-based intervention development.


Effects of dietary supplementation in sport and exercise: a review of evidence on milk proteins and amino acids.
Dietary supplements, especially protein, are used by athletes to achieve the exercise and training daily demands, and have been receiving research focus on their role regarding recovery and performance. Protein supplements are preferred over traditional protein sources because of their ease of availability and use. In addition to consuming a complete protein supplement, such as whey protein, the ingestion of a supplement containing only amino acids has been of interest for promoting skeletal muscle anabolism and high-quality weight loss. The aim of this study was to review the existing evidence on the effects of protein and amino acid supplementation on exercise. The preponderance of evidence suggests that protein supplementation, especially milk proteins, potentiate muscle protein synthesis, lean mass and exercise recovery. Unlike proteins, amino acids supplementation (branched-chain amino acids, glutamine or leucine) results from research are equivocal and are not warranted.


Effect of SARs-CoV-2 pandemic on infection prevention behaviors and bacterial burden of high touch surfaces in a medical/surgical setting.
This study aimed to determine the longitudinal efficacy of ultraviolet germicidal disinfection (UV-C) in a non-terminal disinfection context. Moreover, factors influencing enhanced infection prevention behaviors during the SARS-CoV-2 pandemic were evaluated. Sixty nursing staff from three medical/surgical wards in a large military hospital were recruited for a survey and microbiological sampling of high-touch surfaces (stethoscope, personal electronic device, common access card, and hospital ID badge) and portable medical equipment (wheelchairs and mobile commodes). Surveys included hand hygiene estimates, frequency/method of cleaning items of interest, perception of UV-C, and factors influencing the use of enhanced disinfection tools. Surveys and microbiological samples were performed prior to and after the installation of a rapid, automated ultraviolet disinfection enclosure for staff use. Both time points preceded the SARS-CoV-2 pandemic in the United States. A final survey/sampling time point was carried out eight months after the declaration of the COVID-19 pandemic. Participants' hand hygiene frequency did not increase throughout the study, with > 80% reporting a minimum of 4 hand hygiene events per patient hour. The cleaning frequency of high-touch surfaces (non-clinical) but not portable medical equipment increased after installation of a UV-C disinfection tool and was sustained eight months into the COVID-19 pandemic. While a modest decrease in bacterial burden was observed after UV-C intervention, a more significant reduction was observed across all surfaces during pandemic time sampling, though no detectable decrease in pathogenic contamination was observed at either time point. Motivators of UV-C use included fear of SARS-CoV-2 contamination and transmission, ease of device use, and access to rapid, automated disinfection tools while deterrents reported included technical concerns, lack of time, and preference for other disinfection methods. Automated, rapid-cycle UV-C disinfection can be efficacious for high-touch surfaces not currently governed by infection prevention and control guidelines. The introduction of enhanced disinfection tools like UV-C can enhance the overall cleaning frequency and is correlated with mild decreases in bacterial burden of high-touch surfaces, this is enhanced during periods of heightened infection threat. Evidence from this study offers insights into the factors which prompt healthcare workers to internalize/dismiss enhanced infection prevention procedures.


Quantitative structure--activity correlations of rifamycins as inhibitors of viral RNA-directed DNA polymerase and mammalian alpha and beta DNA polymerases.
Twenty-two 3-substituted rifamycins were tested for inhibition of mammalian alpha and beta DNA polymerase and viral RNA-dependent DNA polymerase ("reverse transcriptase"). Quantitative structure--activity relationships (QSAR) were formulated for the three systems. Inhibition is linearly dependent on the partition coefficient and is highly favored by the presence of bulky hydrazones or oximes. None of these agents proved to be a selective or specific inhibitor of reverse transcriptase. A correlation in terms of log P and (log P)2 was obtained from data on a more closely related set of analogues from a published study. For murine reverse transcriptase, log P0 = 5.1.


Effects of space flight factors on Drosophila.
Drosophila melanogaster flies of strain D-32 were exposed aboard the Soyuz 10 spaceship. An insert with a nutritional medium and insects was placed in a small on-board thermostat (Biotherm II) providing a constant temperature (24 degrees C +/- 1 degree) for Drosophila development. The frequency of dominant lethals was determined in the females. Dominant, autosomal and sex-linked recessive lethals were estimated in hatching virgin males and females; the time of hatching was rigorously fixed. Sex-linked recessive lethals were related to certain stages of gametogenesis. The 1-5 oocyte stage showed an increased sensitivity to space-flight factors as regards the frequency of both dominant and recessive lethals.


Estimating temperature and current using a pair of transceivers in a harbor environment.
Obtaining the horizontal variation of temperature and current fields of a water column usually requires travel-time measurements of acoustic signals traveling along different paths between several horizontally distributed transceivers. This study explores the possibility of using a pair of transceivers deployed in a highly-reverberant harbor environment to extract spatial information of the water. Multipath acoustic propagation of two main arrival groups, i.e., direct arrivals and arrivals reflecting off the harbor side, was observed in the pulse responses measured in the harbor environment during the flood tide. Compared with the direct point measurements of temperature and current, the path-averaged measurements show a similar temporal variation during the experiment, demonstrating the possibility of estimating the spatial variation of the currents and temperatures using the multipath acoustic propagation.


Neural correlates of serial order effect in verbal divergent thinking.
During the course of divergent thinking (DT), the number of generated ideas decreases while the originality of ideas increases. This phenomenon is labeled as serial order effect in DT. The present study investigated whether different executive processes (i.e., updating, shifting, and inhibition) specifically contribute to the serial order effect in DT. Participants' executive functions were measured by corresponding experimental tasks outside of the EEG lab. They were required to generate original uses of conventional objects (alternative uses task) during EEG recording. The behavioral results revealed that the originality of ideas was higher in later stage of DT (i.e., Epoch 2) than in its earlier stage (i.e., Epoch 1) for higher-shifting individuals, but showed no difference between two epochs for lower-shifting individuals. The EEG results revealed that lower-inhibition individuals showed stronger upper alpha (10-13Hz) synchronization in left frontal areas during Epoch 1 compared to during Epoch 2. For higher-inhibition individuals, no changes in upper alpha activity from Epoch 1 to Epoch 2 were found. These findings indicated that shifting and inhibition contributed to create a serial order effect in DT, perhaps because individuals suppress interference from obvious ideas and switch to new idea categories during DT, thus more original ideas appear as time passes by.


Malpositioning of central venous cannula inserted through internal jugular vein after failed cannulation through ipsilateral subclavian vein.
The anesthesiologist is frequently involved in the task of achieving central venous access either for intraoperative uses or postoperative purposes or Intensive Care Unit care. We are usually aware of the common complications of subclavian approach, such as arterial puncture, bleeding, pneumothorax, misplacement in the ipsilateral internal jugular vein (IJV) or contralateral brachiocephalic or subclavian vein. In this case report, we highlight the possibility of malpositioning of central venous cannula inserted through IJV into the anterior extra pleural plane after failed subclavian cannulation attempts.


Statistical analysis of the human middle ear mechanical properties.
Many experimental data on the human middle ear (ME) mechanics and dynamics can be found in the literature. Nevertheless, discussions about the uncertainties of these data are scarce. The present study compiles experimental data on the mechanical properties of the human ME. The summary statistics of mean and standard deviation of the data were collected and the coefficients of variation were computed and pooled. Moreover, the linear correlation and distribution were assessed for the ossicles' mass. Results show that, generally, the uncertainties of the stiffness properties of the tympanic membrane, ligaments, and tendons are larger than the uncertainties of the ossicles' mass. In addition, the uncertainties of the ME response vary across frequency. The vibration measures, such as the stapes' velocity normalized by the sound pressure at the tympanic membrane, are more uncertain than ME input impedance and reflectance. It is expected that the results presented in this study will provide the basis for the development of probabilistic models of the human ME.


High performance liquid chromatography of folates: identification of poly-gamma-glutamate chain lengths of labeled and unlabeled folates.
A sensitive method is described for the identification of the polyglutamate chain lengths of labeled and unlabeled folates in biological extracts. Folates in bacterial or mammalian tissue extracts were quantitatively cleaved to rho-aminobenzoylpolyglutamates. The primary aromatic amines were converted to azo dyes of naphthylethylene diamine and were purified by chromatography on BioGel P2 polyacrylamide columns. The purified azo dyes were reductively reconverted to rho-aminobenzoylpolyglutamates, which were separated according to glutamate chain length by high performance liquid chromatography on a Partisil 10 SAX anionic exchanger. Unlabeled derivatives derived from tissue folates were detected and quantitated by their absorbance at 280 nm. Lactobacillus casei contained folates of glutamate chain length up to 11 with the octa- and nonaglutamates predominating, while tetraglutamates predominated in Streptococcus faecalis. Vitamin in rat liver was a mixture of pteroylmono- to heptaglutamate with the pentaglutamate predominating.


Moringa oleifera methanolic leaves extract induces apoptosis and G0/G1 cell cycle arrest via downregulation of Hedgehog Signaling Pathway in human prostate PC-3 cancer cells.
The inadequacy of effective treatment approaches for prostate cancer enlightens the crucial necessity for the search and emergence of novel and multitasking anticancer substances. Several experimental studies suggested the role of natural compounds in prostate cancer growth inhibition by Hedgehog signaling modulation. In the current study, we suggested the anticancer and apoptosis inducing effects of Moringa oleifera (M. oleifera) were linked to downregulation of Hedgehog pathway in PC-3 prostate cancer cells. We found that M. oleifera leaves methanolic extract exhibited significant anticancerous potential by inducing ROS-mediated apoptosis and activation of caspase-3 activity in prostate cancer. We also observed a dose-dependent G0/G1 cell cycle arrest as well as significant alteration in mRNA expression of apoptosis related and Hedgehog signaling pathway genes by M. oleifera extract treatment. Altogether, these experimental findings demonstrated that M. oleifera may exert antiproliferative apoptosis inducing effects by Hedgehog signaling pathway downregulation. PRACTICAL APPLICATIONS: Moringa oleifera plant, a rich nutrional source, has extensive range of pharmacological applications including antioxidant, anti-inflammatory, and anticancer activity. To best of our knowledge, this could be the first intensive report which presented the inhibitory potential of M. oleifera leaves extract against PC-3 prostate cancer cells via targeting key molecules of Hedgehog signaling. Decreased mRNA expression of GLI1 transcription factor and SMO protein of Hedgehog signaling pathway may be involved in antiproliferative effects of M. oleifera leaves extract against prostate cancer cells. Our study suggested that M. oleifera supplementation might be beneficial for the development and improvement of targeted therapeutic strategies in prostate cancer cells.


Analysis of the infinity-replica symmetry breaking solution of the Sherrington-Kirkpatrick model.
In this work we analyze the Parisi infinity-replica symmetry breaking solution of the Sherrington-Kirkpatrick model without external field using high order perturbative expansions. The predictions are compared with those obtained from the numerical solution of the infinity-replica symmetry breaking equations, which are solved using a pseudospectral code that allows for very accurate results. With these methods we are able to get more insight into the analytical properties of the solutions. We are also able to determine numerically the end point x(max) of the plateau of q(x) and find that lim(T-->0)x(max)(T)>0.5.


Thymosin alpha-1 as adjunct for conventional therapy of malignant tumors: a review.
T alpha 1, a 28-amino-acid peptide, is derived from PT alpha, which is an intracellular, nonsecretory protein of unknown function. Both T alpha 1 and PT alpha are found in the blood of normal individuals. Subcutaneous and intramuscular injections of T alpha 1 in doses up to 9.6 mg/m2 are tolerated without side effects, and 0.9 mg/m2 injections raise the serum level approximately 30-fold after 1 hr of administration, which slowly returns to baseline within 24 hr. In vitro, and perhaps in vivo, T alpha 1 restores normal T-cell function. It increases IL-2 production and IL-2 receptors in normal mitogen-stimulated T cells and stimulates IL-3 production in immunocompromised mice. The dose-response relationship for these effects is not linear and may be bimodal. T alpha 1 binds to VIP receptors and inhibits in vitro and xenograft growth of non-SCLC cell lines. In patients with nonbulky carcinomas who have received standard therapy, T alpha 1 is possibly effective in prolonging the time to relapse and in improving survival. At present there is a great need to clearly define the clinical role of T alpha 1 in cancer patients. A major problem encountered in studies with T alpha 1 will, however, be the present lack of knowledge with regard to its mechanism in effecting tumor growth. It is not at all clear whether its immunomodulatory functions, its interaction with VIP receptors, or none of these mechanisms are related to its antineoplastic activities. In addition, the apparent nonlinear dose-response relationship will make it difficult to choose a reasonable dosing schedule for clinical trials. This is particularly apparent in light of the experimental animal data summarized above where a tumor response was seen at doses of 4 micrograms/kg and 400 micrograms/kg but not at 0.4 microgram/kg and 40 micrograms/kg. This dose range could conceivably be given to humans since 9.6 mg/m2, the maximum dose given to humans without major side effects to date, is roughly equivalent to 250 micrograms/kg. At this time a reasonable clinical approach would be a well-designed risk factor stratified phase III clinical trial using 0.9 mg/m2 T alpha 1 subcutaneously twice a week compared to a control group to substantiate the data reported by Schulof et al. Before such data are available, T alpha 1 should not be used in clinical oncology.


Music Therapy as a Nonpharmacological Intervention for Anxiety in Patients with a Thought Disorder.
Music therapy has been identified as a non-pharmacological adjunct therapy to treat anxiety. This QI project aimed to assess the effects of music therapy on anxiety in a sample of patients hospitalized with a thought disorder. Participants were assessed pre- and post-group using a visual analog scale for anxiety. The intervention significantly reduced VAS scores from 3.1 pre-intervention to .897 immediately post-intervention (p = 0.008). This data suggests that music therapy may be beneficial in the short term for this population and is a low risk intervention that provides positive outcomes without the risks associated with medications, seclusion, and restraint.


Comparison of male conflict behavior in chimpanzees (Pan troglodytes) and bonobos (Pan paniscus), with specific regard to coalition and post-conflict behavior.
Coalitions among males during within group conflicts have a strong influence on the competitive and social environment within social groups. To evaluate possible variation in the occurrence of such coalitions in our closest relatives, chimpanzees and bonobos, we compared male aggression and coalitionary behavior in two natural communities, one of each species, with a similar size and composition. Furthermore we compared affiliative behavior that might be related to coalition formation among males. We found higher frequencies of aggression and a greater likelihood to form coalitions during within-group conflicts among wild male chimpanzees at Taï compared to wild male bonobos at LuiKotale. The species differed in the predominant sex of the male coalition partners, with male bonobos forming coalitions more often with females, while male chimpanzees formed coalitions more often with other males. Compared to male bonobos, male chimpanzees showed higher rates of grooming and tended to reconcile more conflicts with other males. Overall our results showed lower frequencies of reconciliation among bonobos than those described in captivity and at artificial feeding sites. These findings add to the evidence that male cooperation and conflict resolution are potentially very different in bonobos and chimpanzees, despite the fact that these two species are closely related, live in multi-male, multi-female communities with a high degree of fission-fusion dynamics and have female-biased migration patterns. Given the correlation between aggressive, cooperative and some affiliative patterns within the species in our study, we hypothesize that the fitness benefits of male relationships are greater in chimpanzees compared to bonobos.


[Numerical study on inspiratory flows in two and three generation bronchi of human lung airways].
The main physiological function of respiratory system is exchange of oxygen and carbon dioxide between atmosphere and blood. Its physiological process is closely related with air flow and transport in respiratory airway. This paper studies numerically the inspiratory flows in a two generation and a three generation bronchial airway. The numerical results of the two generation bronchi show that the present computations fit the available experiments very well. For three generation bronchi, no separation appears within the whole airway under normal breathing rate, which is contrary to the occurrence of separation at even low Reynolds number by the previous two dimensional models. Strong secondary flow phenomenon, skew and m-shaped main flow velocity profiles are found in the airways due to geometrical curvature and bifurcation. These increase shear stress acting on the inner wall as well as on the anterior and posterior wall in the bifurcating airways. In the end bronchi of the three generation airway, the mass flow rates in medial and lateral bronchi are unequal, and the mass flow ratio between the medial and the lateral bronchi is 1.2 at the flow conditions considered.


Development and validation of an occupational health triage tool.
As work and health are closely interlinked, it is important to carefully monitor employees. However, limited resources restrict in-depth follow-up. This study was aimed to develop a low-cost screening instrument for employees' overall health status, that can be used across industries and that allows triaging workers to in-depth health surveillance in case of indications of health or functioning problems. We developed a new questionnaire-based algorithm built on multiple predictors to assess the need for further follow-up. We used a systematic review, Delphi panel (n = 9) and focus group (n = 5) to determine the predictors, tested for language pitfalls in a pilot study and evaluated the questionnaire's validity in two separate studies. Study 1 (n = 60) analysed the discriminatory power of the instrument by comparing it to the assessment of an occupational physician in a sample of employees from diverse occupational settings. Study 2 (n = 869) appraised the factor structure and internal consistency of the screening tool in a sample of employees from the hospital sector. Risk factors, current physical and mental health, functioning, absenteeism, job satisfaction and lifestyle were identified as the most relevant predictors. Study 1 showed the survey had good criterion validity (area under the curve = 0.72). Study 2 (N = 869, 28% response) demonstrated the internal consistency (Cronbach's α = 0.94), and a factor analysis confirmed a second-order factor structure with adequate model fit (comparative fit index = 0.96, root mean square error of approximation = 0.04 and standardized root mean square residual = 0.07). This questionnaire can be used to triage workers for occupational health follow-up and can, additionally, be useful to describe the epidemiology of work-related illness.


The immediate effect of kinesiology taping on muscular imbalance for infants with congenital muscular torticollis.
To investigate the immediate effect of kinesiology taping (KT) on muscular imbalance in the lateral flexors of the neck. A retrospective study. Twenty-eight infants with congenital muscular torticollis and muscular imbalance in the lateral flexors of the neck were chosen consecutively. Data regarding the Muscle Function Scale (MFS) score before and after the first taping session were obtained from the records. A significant decrease in the difference between the MFS scores was found after KT was applied (P < .001). Significantly greater scores were noted on the unaffected side after KT (P = .02) and significantly lower scores were noted on the affected side after KT (P = .003). Multiple regression demonstrated that the MFS score on the unaffected side (P < .001) and use of the muscle-relaxing technique (P = .009) were significantly associated with a decrease in the difference between the MFS scores of the 2 sides. KT has an immediate effect on muscular imbalance in infants with congenital muscular torticollis.


A didactical note on the advantage of using two parameters in Hopf bifurcation studies.
In order to maximize the information that a linearized stability analysis provides, one should work with two free parameters rather than one. Moreover, it is recommended to first consider coefficients in the characteristic equation as parameters and in a second step (try to) invert the map that defines the coefficients in terms of the parameters as they occur in the original equation. Our aim is to substantiate these claims by way of a delay equation example taken from the literature.


Endometriosis and Risk of Cardiovascular Disease: Systematic Review and Meta-Analysis.
Background: Endometriosis is a common disease affecting 10% of reproductive-age women globally and is associated with chronic systemic inflammation. Some studies suggest that women with endometriosis have a higher risk of cardiovascular disease, whereas others have conflicting findings. This study aims to further investigate the association between endometriosis and cardiovascular disease. Methods: A systematic review was conducted using the EMBASE and MEDLINE databases from inception to October 2022. The search strategy comprised terms for "endometriosis" and "cardiovascular disease." Eligible studies had to include one group of patients with endometriosis and another group of individuals without endometriosis. The study must then compare the incidence or prevalence of cardiovascular disease (major adverse cardiovascular events [MACE], ischemic heart disease [IHD], cerebrovascular accident [CVA], or peripheral artery disease [PAD]). Results: A total of 5,401 articles were identified, and 9 studies were eligible for meta-analysis. Pooled analysis showed an increased prevalence of IHD (pooled odds ratio [OR]: 1.22; 95% confidence interval [95% CI]: 0.74-2.02), CVA (pooled OR: 1.28; 95% CI: 1.07-1.53), and PAD (pooled OR: 1.55; 95% CI: 1.35-1.78). Pooled analysis showed an increased incidence of MACE (pooled hazard ratio [HR]: 1.23; 95% CI: 1.14-1.33), IHD (pooled HR: 1.43; 95% CI: 1.28-1.59), and CVA (pooled HR: 1.20; 95% CI: 1.11-1.30). Conclusions: This systematic review and meta-analysis found a statistically significant association between endometriosis and increased risk of cardiovascular disease (MACE, IHD, CVA, PAD).


[Effect of histones on cell permeability, protein and RNA synthesis and RNA stability in Aerobacter cloaceae].
The histones of calf thymus were found to change the permeability of the cells of Aerobacter cloaceae, without producing any noticeable effect on their viability. Concomitant depolymerization of the cellular RNA indicates destruction of the ribosomes. The increased synthesis of RNA in interpreted as a manifestation of reparatory processes. Protein synthesis, virtually unaffected in the resting cells, was inhibited to some extent in the growing culture treated with histones. Some considerations concerning the mode of action of histones at the intracellular level are presented.


Characterization and quantitative analysis of phenolic derivatives in Longxuetongluo Capsule by HPLC-DAD-IT-TOF-MS.
Longxuetongluo Capsule (LTC), which is derived from the total phenolic extract of Chinese dragon's blood, has been proved to be safe as well as effective towards ischemic stroke. However, the effective material basis remains unclear. The present study thereby focused on the clarification of the qualitative and quantitative properties for the phenolic derivatives in LTC. Regarding homolog-focused chemical profiling, the mass fragmentation patterns of the primary subtypes of phenolic compounds such as homoisoflavanones, flavanes, chalcones, and flavonoid oligomers were summarized by assaying authentic references with hybrid ion trap time-of-flight mass spectrometry, and the chemical structures of 124 phenolic compounds, in total, were unambiguously or tentatively annotated in LTC by matching the accurate mass spectral profiles with the proposed mass cracking rules and those reference substances. Afterwards, simultaneous determination of 12 primary phenolic compounds was carried out in different batches of LTC using HPLC-DAD, after that the method was proved to be accurate, precise, and reproducible according to diverse method validation assays. The obtained findings are expected to be meaningful for clarifying the effective substances and quality assessment of LTC.


Change in aggregation state of insulin upon conjugation with 5-dimethylaminonaphthalene-1-sulfonyl group.
Change in aggregation state of insulin upon conjugation with 5-dimethylaminonaphthalene-1-sulfonyl (DNS) group was investigated at neutral pH. DNS group was introduced exclusively into B1 phenylalanine, the N-terminus of the B-chain of insulin. The association state of insulin shifted toward a more highly aggregated one upon conjugation, depending on the mole fraction (d) of DNS group to insulin monomer; at d equal 0.3 the equilibrium between dimer and hexamer was dominant over the range of 1-600 microM, while at d equal 1.0-1.5 DNS-insulin formed a larger aggregate (dodecamer) which is stable over the range of 67-600 microM. The dissociation constant of dimer-hexamer equilibrium at d=0.3 was evaluated to be 2.5 x 10(-10) M2 from the fluorescence anisotropy of the DNS group, which was about one order of magnitude smaller than that of the dimer-hexamer equilibrium in native insulin. Spectroscopic data and fluorescence decay analyses indicated that there exist at least two different environments surrounding the dye bound to B1 phenylalanine and that they are both relatively hydrophilic. It is considered that the major part of DNS group has excitation and emission maxima at longer wavelength with relatively low quantum yield, while the minor part has excitation and emission maxima at shorter wavelengths with relatively high quantum yield. The fluorescence lifetime of the dye was modified by the change in quaternary structure of DNS-lifetime of the dye was modified by the change in quaternary structure of DNS-insulin. Remarkable depolarization of DNS fluorescence was observed at d equal 1.0 and d equal 1.5 due to energy transfer between DNS groups conjugated to B1 phenylalanine in the hexamer or the dodecamer. Critical transfer distance for inter-DNS energy transfer was evaluated to be 15 A. From the molecular model of the insulin crystal, this energy transfer is ascribed to the close proximity, within about 15 A, between DNS groups in dimer units of the hexamer or the dodecamer.


Chromosome location of ISSR markers and genes controlling seed germination under drought stress in wheat-barley disomic addition lines.
Alien disomic addition lines are valuable genetic resources for breeding programs under wide hybridization. The present study was carried out to identify the chromosome location of ISSR markers and genes controlling seed germination under drought stress in wheat-barley disomic addition lines. Germination experiment was performed at 0, -4 bar and -8 bar levels in a completely randomized design with three replications. The Germination Index, Germination Percentage, Coefficient of Germination Velocity, Mean Germination Time, Mean Germination Daily, and Plantlet Growth Speed were measured. Based on karyotype analysis, the presence of addition chromosomes was confirmed. The IS10 (0.494) and IS15 (0.395) primers showed the greatest polymorphism among the addition lines. The primers amplified most parts of the chromosomes 2H, 3H, and 7H, indicating these ISSR primers are located on these chromosomes. It is also indicated that most of the genes responsible for the seed germination under drought stress are located on chromosomes 4H and 5H.


Psychological stress and pain in wound care, part 3: management.
There is increasing evidence to support a relationship between psychological stress and delayed wound healing. Management should therefore include interventions that minimise patient distress, which will include social support and coping skills.


Glutamine and α-ketoglutarate as glutamate sources for glutathione synthesis in human erythrocytes.
Glutathione (GSH) is an intracellular antioxidant synthesized from glutamate, cysteine and glycine. The human erythrocyte (red blood cell, RBC) requires a continuous supply of glutamate to prevent the limitation of GSH synthesis in the presence of sufficient cysteine, but the RBC membrane is almost impermeable to glutamate. As optimal GSH synthesis is important in diseases associated with oxidative stress, we compared the rate of synthesis using two potential glutamate substrates, α-ketoglutarate and glutamine. Both substrates traverse the RBC membrane rapidly relative to many other metabolites. In whole RBCs partially depleted of intracellular GSH and glutamate, 10 mm extracellular α-ketoglutarate, but not 10 mm glutamine, significantly increased the rate of GSH synthesis (0.85 ± 0.09 and 0.61 ± 0.18 μmol·(L RBC)(-1) ·min(-1), respectively) compared with 0.52 ± 0.09 μmol·(L RBC)(-1) ·min(-1) for RBCs without an external glutamate source. Mathematical modelling of the situation with 0.8 mm extracellular glutamine returned a rate of glutamate production of 0.36 μmol·(L RBC)(-1) ·min(-1), while the initial rate for 0.8 mM α-ketoglutarate was 0.97 μmol·(L RBC)(-1) ·min(-1). However, with normal plasma concentrations, the calculated rate of GSH synthesis was higher with glutamine than with α-ketoglutarate (0.31 and 0.25 μmol·(L RBC)(-1) ·min(-1), respectively), due to the substantially higher plasma concentration of glutamine. Thus, a potential protocol to maximize the rate of GSH synthesis would be to administer a cysteine precursor plus a source of α-ketoglutarate and/or glutamine.


Challenges in natural health product research: The importance of standardization.
Before there can be acceptance of natural health products (NHPs) or "phytomedicines" by the Western medical community, questions related to active ingredients, mechanisms of action, toxicology, and drug interactions will need to be satisfactorily addressed. Since NHPs are generally manufactured from highly variable raw materials, identifying the therapeutically active ingredients can be challenging. Standardization according to all known bioactive components is critical to ensure consistent pharmacological and clinical results. CV Technologies, Inc. has made great strides in resolving these challenges through the patented technology, ChemBioPrint. During early ChemBioPrint product development, the optimal active components of a natural extract are identified and characterized chemically (chemical fingerprinting) and pharmacologically through a variety of activity assays (biological fingerprinting). Subsequent manufacturing steps ensure each batch is standardized accordingly and has consistent composition and efficacy. Case studies will be presented on two commercially available ChemBioPrint products: COLD-fX (an immune-modulator) and REMEMBER-fX (a neuro-modulator). Unique and important structure-function relationships exist between the major classes of bioactive molecules from the shared source material of these two products, Panax quinquefolius. Through numerous published and ongoing clinical trials and pharmacological studies, these ChemBioPrint products have been shown to be consistent, safe and effective. The future directions of NHP research will be discussed, including the requirements for accurate reporting of study results related to ingredient and standardization descriptions.


Percutaneous coronary intervention in a single coronary artery originating from the right sinus of Valsalva.
The origin of the left coronary artery (LCA) from the right sinus of Valsalva is a rare congenital anomaly that may be associated with myocardial infarction and sudden or exercise-related death. We report a rare case of a single coronary artery originating from the right coronary sinus and bifurcating into LCA and right coronary artery (RCA). The RCA was found to contain a significant flow-limiting lesion that was successfully treated with percutaneous coronary intervention. In this short report, we discuss the variations in anomalous LCA originating from the right coronary sinus and their clinical implications.


Chiral Monitoring Across Both Enantiomeric Excess and Concentration Space: Leveraging Quantum Cascade Lasers for Sensitive Vibrational Circular Dichroism Spectroscopy.
Recently, high-throughput quantum cascade laser-based vibrational circular dichroism (QCL-VCD) technology has reduced the measurement time for high-quality vibrational circular dichroism spectra from hours to a few minutes. This study evaluates QCL-VCD for chiral monitoring using flow-through measurement of a changing sample in a circulating loop. A balanced detection QCL-VCD system was applied to the enantiomeric pair R/S-1,1'-bi-2-naphthol in solution. Different mixtures of the two components were used to simulate a racemization process, collecting spectral data at a time resolution of 6 min, and over three concentration levels. The goal of this experimental setup was to evaluate QCL-VCD in terms of both molar and enantiomeric excess (EE) sensitivity at a time resolution relevant to chiral monitoring in chemical processes. Subsequent chemometric evaluation by partial least squares regression revealed a cross-validated prediction accuracy of 2.8% EE with a robust prediction also for the test data set (error = 3.5% EE). In addition, the data set was also treated with the least absolute shrinkage and selection operator (LASSO), which also achieved a robust prediction. Due to the operating principle of LASSO, the obtained coefficients constituted a few discrete spectral frequencies, which represent the most variance. This information can be used in the future for dedicated QCL-based instrument design, gaining a higher time resolution without sacrificing predictive capabilities.


Rapid evaluation of catalysts and MAO activators by kinetics: what controls polymer molecular weight and activity in metallocene/MAO catalysts?
The influence of methylaluminoxane (MAO) catalyst activators of different concentrations and preparative histories on the performance of 1-hexene polymerisations was investigated by kinetic methods, using rac-Me2Si(2-Me-Benz[e]Ind)2ZrCl2 as the standard catalyst precursor. Fast sampling and analysis allow the time dependence of monomer conversion and the growth of the number-average polymer molecular weight to be determined at a sufficiently short timescale to make this a feasible method for routine catalyst evaluation. Differences in productivity, polymer molecular weight and active species count are shown to be primarily a linear function of the trimethylaluminium concentration. The results in toluene and heptane as solvents are compared; the data show that the inferior performance in heptane is due to a substantially lower active species concentration.


Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation.
The active form of vitamin D3, 1alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] is key mediator of calcium homeostasis and is a component of the complex homeostatic system of the skin. 1,25-(OH)2D3 regulates cellular differentiation and proliferation and has broad potential as an anticancer agent. Oligonucleotide microarrays were used to assess profiles of target gene regulation at several points over a 48 h period by the low calcemic 1,25-(OH)2D3 analog EB1089 in human SCC25 head and neck squamous carcinoma cells. One hundred fifty-two targets were identified, composed of 89 up- and 63 down-regulated genes distributed in multiple profiles of regulation. Results are consistent with EB1089 driving SCC25 cells toward a less malignant phenotype, similar to that of basal keratinocytes. Targets identified control inter- and intra-cellular signaling, G protein-coupled receptor function, intracellular redox balance, cell adhesion, and extracellular matrix composition, cell cycle progression, steroid metabolism, and more than 20 genes modulating immune system function. The data indicate that EB1089 performs three key functions of a cancer chemoprevention agent; it is antiproliferative, it induces cellular differentiation, and has potential genoprotective effects. While no evidence was found for gene-specific differences in efficacy of 1,25-(OH)2D3 and EB1089, gene regulation by 1,25-(OH)2D3 was generally more transient. Treatment of cells with 1,25-(OH)2D3 and the cytochrome P450 inhibitor ketoconazole produced profiles of regulation essentially identical to those observed with EB1089 alone, indicating that the more sustained regulation by EB1089 was due to its resistance to inactivation by induced 24-hydroxylase activity. This suggests that differences in action of the two compounds arise more from their relative sensitivities to metabolism than from differing effects on VDR function.


[The electroporation effects of high power pulse microwave and electromagnetic pulse irradiation on the membranes of cardiomyocyte cells and the mechanism therein involved].
Though there is ongoing public concern on potential hazards and risk of electromagnetic radiation, the bioeffects mechanism of electromagnetic fields remains obscure. Heart is one of the organs susceptive to electromagnetic fields (EMF). This study was designed to assess the influence of high power pulse microwave and electromagnetic pulse irradiation on cardiomyocytes, to explore the critical mechanism of electromagnetic fields, and to explain the regular course of injury caused by exposure to pulse EMF. Cultured cardiomyocytes were irradiated by high power pulse microwave and electromagnetic pulse first, then a series of apparatus including atom force microscope, laser scanning confocal microscope and flow cytometer were used to examine the changes of cell membrane conformation, structure and function. After irradiation, the cardiomyocytes pulsated slower or stop, the cells conformation was abnormal, the cells viability declined, and the percentage of apoptosis and necrosis increased significantly (P< 0.01). The cell membrane had pores unequal in size, and lost its penetration character. The concentration of Na+, K+, Ca2+, Cl-, Mg2+, Ca2+ and P3+ in cell culture medium increased significantly (P< 0.01). and the concentration of Ca2+ in cells ([Ca2+]i) decreased significantly (P<0.01). The results indicated that cardiomyocytes are susceptible to non-ionizing radiation. Pulse electromagnetic field can induce cardiomyocytes electroporation, and can do great damage to cells conformation, structure and function. Electroporation is one of the most critical mechanisms to explain the athermal effects of electromagnetic radiation.