Implication of 4E-BP1 protein dephosphorylation and accumulation in pancreatic cancer cell death induced by combined gemcitabine and TRAIL.
Pancreatic cancer cells show varying sensitivity to the anticancer effects of gemcitabine. However, as a chemotherapeutic agent, gemcitabine can cause intolerably high levels of toxicity and patients often develop resistance to the beneficial effects of this drug. Combination studies show that use of gemcitabine with the pro-apoptotic cytokine TRAIL can enhance the inhibition of survival and induction of apoptosis of pancreatic cancer cells. Additionally, following combination treatment there is a dramatic increase in the level of the hypophosphorylated form of the tumour suppressor protein 4E-BP1. This is associated with inhibition of mTOR activity, resulting from caspase-mediated cleavage of the Raptor and Rictor components of mTOR. Use of the pan-caspase inhibitor Z-VAD-FMK indicates that the increase in level of 4E-BP1 is also caspase-mediated. ShRNA-silencing of 4E-BP1 expression renders cells more resistant to cell death induced by the combination treatment. Since the levels of 4E-BP1 are relatively low in untreated pancreatic cancer cells these results suggest that combined therapy with gemcitabine and TRAIL could improve the responsiveness of tumours to treatment by elevating the expression of 4E-BP1.


The Effects of Statins on Neurotransmission and Their Neuroprotective Role in Neurological and Psychiatric Disorders.
Statins are among the most widely used drug classes in the world. Apart from their basic mechanism of action, which is lowering cholesterol levels, many pleiotropic effects have been described so far, such as anti-inflammatory and antiatherosclerotic effects. A growing number of scientific reports have proven that these drugs have a beneficial effect on the functioning of the nervous system. The first reports proving that lipid-lowering therapy can influence the development of neurological and psychiatric diseases appeared in the 1990s. Despite numerous studies about the mechanisms by which statins may affect the functioning of the central nervous system (CNS), there are still no clear data explaining this effect. Most studies have focused on the metabolic effects of this group of drugs, however authors have also described the pleiotropic effects of statins, pointing to their probable impact on the neurotransmitter system and neuroprotective effects. The aim of this paper was to review the literature describing the impacts of statins on dopamine, serotonin, acetylcholine, and glutamate neurotransmission, as well as their neuroprotective role. This paper focuses on the mechanisms by which statins affect neurotransmission, as well as on their impacts on neurological and psychiatric diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), vascular dementia (VD), stroke, and depression. The pleiotropic effects of statin usage could potentially open floodgates for research in these treatment domains, catching the attention of researchers and clinicians across the globe.


Is the duty of candour under threat?
Emeritus Professor Alan Glasper, University of Southampton, dissects the case of paediatrician Dr Hadiza Bawa-Garba and registered nurse Isabel Amaro, and how their convictions might affect the duty of candour legislation.


Emergency management of pelvic fractures.
Pelvic fractures are relatively uncommon, accounting for 1-3% of all fracture. Around 60% occur in men. This article discusses the multidisciplinary management of pelvic ring disruptions resulting from high energy transfer.


Allergic skin diseases.
The skin is one of the largest immunologic organs and is affected by both external and internal factors, as well as innate and adaptive immune responses. Many skin disorders, such as atopic dermatitis, contact dermatitis, urticaria, angioedema, psoriasis, and autoimmune blistering disorders, are immune mediated. Most of these diseases are chronic, inflammatory, and proliferative, in which both genetic and environmental factors play important roles. These immunologic mechanisms might have implications for potential targets of future therapeutic interventions.


Aneuploidy screening: what test should I use?
Screening for the risk of fetal aneuploidy can be effectively performed in either the first or second trimester. When obtained independently, the interpretation of those data is straightforward. However, the effectiveness of screening can be enhanced by combining studies performed in each trimester in a variety of ways. In this commentary we will define and discuss both the advantages and disadvantages of using integrated, stepwise, sequential or contingency screening for risk assessment of fetal aneuploidy.


Biomarkers of opiate use.
The interpretation of toxicological findings is critical for the thorough investigation of the use and abuse of psychoactive substances. A positive analytical result for a sample taken could usually result in criminal proceedings and a punitive outcome for the defendant whose sample was analysed. The detection of markers of illicit opiate misuse is important both in the management of substance misuse and in the postmortem identification of illicit opiate use. The aim of this study was to emphasise the role of opiate biomarkers available at the laboratory and in the clinical environment. Urine remains the biological tool of choice for qualitative detection of illicit drug use in a clinical setting, while quantitative accuracy remains strictly the domain of blood. Accurate interpretation of the screening tests within a clinical setting alongside other relevant information remains the key to the usefulness of any test. Moreover, the finding of a morphine/codeine concentration ratio in blood exceeding unity is a strong evidence that the person had used heroin, as opposed to having taken a prescription analgesic drug containing codeine.


Provider chart audits and outreach to parents: impact in improving childhood immunization coverage and immunization information system completeness.
Examine impact of provider chart audits and parental outreach in improving immunization coverage among children not up-to-date (NUTD) for immunizations in Philadelphia's immunization information system (IIS). We identified 10-month-old children NUTD for age-appropriate immunizations using Philadelphia's IIS. Immunization rates at 10, 13, and 19 months were compared before and after contact with providers and parents. Of 5 610 children NUTD in the IIS at 10 months and living in areas with populations at risk for underimmunization, provider chart audits indicated that 3 612 (64%) were actually up-to-date (UTD); the majority of these (2 203) received additional age-appropriate immunizations and were also UTD at 19 months. Of 1 998 children truly NUTD at 10 months, half received overdue immunizations by 13 months following contact with parents via telephone, postcards, and home visits, but only 23 percent were UTD for age-appropriate vaccines at 19 months. Provider chart audits improved IIS data completeness, indicating that providers need to submit more complete and timely data to the IIS. Outreach to parents likely contributed to half of the children NUTD at 10 months receiving overdue immunizations by 13 months. However, most were again NUTD at 19 months, indicating that outreach efforts should be continued through 19 months or until children are brought UTD. Furthermore, in spite of outreach, about half of the NUTD children were not brought UTD by 13 or 19 months. New strategies should be developed to ensure that these children receive recommended vaccinations.


Mathematical modeling of stem cell proliferation.
The mathematical models prevalently used to represent stem cell proliferation do not have the level of accuracy that might be desired. The hyperbolastic growth models promise a greater degree of precision in representing data of stem cell proliferation. The hyperbolastic growth model H3 is applied to experimental data in both embryonic stem cells and adult mesenchymal stem cells. In the embryonic stem cells the results are compared with other popular models, including the Deasy model, which is used prevalently for stem cell growth. In the case of modelling adult mesenchymal stem cells, H3 is also successfully applied to describe the proliferative index. We demonstrated that H3 can accurately represent the dynamics of stem cell proliferation for both embryonic and adult mesenchymal stem cells. We also recognize the importance of additional factors, such as cytokines, in determining the rate of growth. We propose the question of how to extend H3 to a multivariable model that can include the influence of growth factors.


Stroke awareness among Georgia adults: epidemiology and considerations regarding measurement.
To design and evaluate interventions for reducing the impact of stroke in Georgia, we assessed knowledge of signs, risk factors, and burden of stroke. Adults in Georgia were studied with a random digit dial telephone survey. Answering an unaided question, 39% of 602 respondents named > or =1 stroke warning sign. Awareness was considerably greater when assessed with prompted questions. Most respondents (70%) said they would call 911 if someone had a stroke; almost all (95%) considered stroke an emergency. Risk factor awareness ranged from 97% (previous stroke) to 69% (diabetes). Altogether, 6% reported having had a stroke; 48% reported a stroke in their family. Georgia adults have low awareness of stroke warning signs. Our findings underscore the importance of conducting an effective educational campaign. Furthermore, a need exists for questions on stroke awareness that approximate more closely the situation in which a person must identify a potential stroke.


An isokinetic investigation of contractile mode's effect on the elbow flexors.
Healthy, sedentary, college-age subjects (n = 16) performed concentric or eccentric maximal unilateral isokinetic (1.08 rad s(-1)) elbow flexor contractions (4 sets of 12 repetitions) to fatigue as physiological data were concurrently collected. Net caloric expenditure was determined using indirect calorimetry, whereas the electromyogram examined root mean square (RMS) and mean power frequency (MPF) values for the biceps brachii, brachioradialis, and palmaris longus. Eccentric exercise resulted in significantly greater (p < 0.05) absolute (total work per kilocalorie) and relative (total work per kilocalorie per kilogram) exercise efficiency values. Concentric biceps brachii and brachioradialis RMS values were significantly (p < 0.05) greater than corresponding eccentric values, suggesting greater motor unit recruitment. Concentric MPF values, a measure of motor unit fatigue, showed significantly (p < 0.05) greater before and after decrements following exercise for the biceps brachii and brachioradialis. Greater exercise efficiency with less motor unit recruitment and fatigue results from eccentric exercise.


Temporal Trends in the Unmet Health Care Needs of Canadian Stroke Survivors.
Stroke survivors have higher unmet health care needs than the general population. However, it is unclear whether such needs have changed over time, and whether these have been affected by the introduction of integrated systems of stroke care. We used data from the Canadian Community Health Surveys between 2000 and 2014. We developed multivariable log-binomial generalized estimating equations to obtain adjusted risk ratios (aRRs) of unmet health care needs in stroke survivors compared to the general population, and over time. We conducted a difference in differences analysis to determine the association between the implementation of integrated systems of stroke care and unmet health care needs. Data from 350,084 respondents were included in the study; 8072 (2.3%) were stroke survivors. Compared to the general population, stroke survivors were more likely to report unmet health care needs (aRR 1.27; 95% CI, 1.22-1.32). The unmet health care needs reported by stroke survivors were lower after compared to before 2006 (15.8% vs. 31.9%, P < 0.001). After accounting for temporal trends, there was no association between the implementation of integrated systems of stroke care and change in unmet health care needs of stroke survivors. However, this requires cautious interpretation due to limitations in the data available for this study. Unmet health care needs of stroke survivors have reduced over time but remain higher than the general population. Future research should focus on identifying stroke- and policy-related factors to mitigate disparities in health care access for stroke survivors.


Mortality associated with respiratory function and symptoms in advanced age. The Framingham Study.
Pulmonary function, cigarette smoking, and respiratory symptoms were determined in 3,133 men and women at the 13th examination of the Framingham Study (1972 to 1976). Deaths in the subsequent 10-yr period were identified. Forced expiratory volume in one second and forced vital capacity were standardized for body size by dividing by the square of the height (FEV1/ht2, FVC/ht2). As expected, mean values of these pulmonary function measures were lower in women compared to those in men, older participants compared to younger, smokers compared to nonsmokers, and those with respiratory symptoms compared to those without. In men and women under 70 yr of age and women over 70 yr of age, FEV1/ht2 was inversely related to mortality after adjustment for age, smoking, and respiratory symptoms. In older men, FEV1/ht2 was not related to mortality, but symptoms of dyspnea were associated with increased risk of death.


Compact, single-frequency all-fiber Q-switched laser at 1 microm.
We demonstrate a unique, all-fiber, actively Q-switched laser operating in the 1 microm region. The laser is compact, single mode, single frequency, highly polarized, and exhibits high peak power. The laser cavity is constructed without external coupling, utilizing fiber Bragg gratings that permit feedback at only a single polarization. By using a piezoelectric to press the fiber and modulate the fiber birefringence, the cavity is switched between high and low loss states, permitting Q-switching. We demonstrate this Q-switching at repetition rates up to 700 KHz.


Development of On-Demand Antiviral Electrostatic Precipitators with Electrothermal-Based Antiviral Surfaces against Airborne Virus Particles.
Particulate matter, including airborne pathogens, is of particular concern because it can cause the spread of diseases through aerosol transmission. In this study, a new concept is proposed: on-demand antiviral electrostatic precipitators (ESPs) with electrothermal-based antiviral surfaces. We applied electrothermal-based antiviral surfaces to air-purifying applications and demonstrated that the proposed method is effective with regard to collecting airborne virus particles on collection plates in a two-stage ESP. With alternating current power, MS2 bacteriophage and H1N1 viruses were completely deactivated after exposure to 50 °C for 30 min. This remarkable antiviral performance via electrothermal effects indicates that on-demand platforms for self-antiviral surfaces can perform sterilization immediately without generating secondary pollutants, thus effectively preventing the spread of infectious microorganisms in public places. We believe that the results of this study can provide useful guidelines for the design and realization of practical and wearable devices for antiviral air-purifying applications.


[A retrospective analysis of 147 cases of orbital exenteration].
Objective: To investigate the main indications and prognosis of patients undergoing orbital exenteration (OE). Methods: It was a retrospective case series study. The medical records were collected of patients who underwent OE surgery at Beijing Tongren Hospital from January 2007 to December 2021, and their general information, tumor characteristics, lymph node metastasis, diagnosis and treatment, specific surgical techniques, pathological diagnosis and prognosis were analyzed. Kaplan-Meier survival curves were used to evaluate overall survival and recurrence-free survival. Results: A total of 147 patients were included, with a median age of 58 (48, 68) years. Among them, 82 patients (55.8%) were male and 65 (44.2%) were female, and all underwent unilateral OE. Five patients (3.4%) had benign lesions. Among the 142 patients with malignant tumors, conjunctival malignancies (37.3%) were the most common, followed by eyelid (29.6%), orbital (19.0%), and ocular (14.1%) malignancies. Among the 53 patients with conjunctival tumors, 38 (71.7%) had conjunctival melanoma and 14 (26.4%) had squamous cell carcinoma. Among the 42 patients with eyelid malignancies, 19 (45.2%) had sebaceous gland carcinoma and 16 (38.1%) had basal cell carcinoma. Among the 20 patients with ocular malignancies, 10 (50.0%) had choroidal melanoma and 9 (45.0%) had retinoblastoma. The most common pathological types among the 142 patients with malignant tumors were melanoma (51 cases, 35.9%), squamous cell carcinoma (20 cases, 14.1%), sebaceous gland carcinoma (19 cases, 13.4%), and basal cell carcinoma (16 cases, 11.3%). Of the 135 patients included in the survival analysis, all 5 patients with benign lesions were alive at the last follow-up. The median follow-up time for the 130 patients with malignant tumors was 6.9 (2.5, 6.9) years, ranging from 0.2 to 14.0 years. The overall survival rates at 1, 3, and 5 years after surgery were 90.9% (95%CI: 85.8%-96.0%), 68.4% (95%CI: 59.6%-77.2%), and 60.1% (95%CI: 50.5%-69.7%), respectively. The recurrence-free survival rates of patients with and without lymph node metastasis before surgery were 57.6% and 56.7%, respectively (OR=1.062, 95% CI: 0.525-2.148, P=0.864), and the overall survival rates were 61.5% and 57.7%, respectively (OR=1.019, 95% CI: 0.512-2.033, P=0.957), with no significant differences both. The recurrence-free survival rates of patients with melanoma (47 cases) and non-melanoma (83 cases) were 40.4% and 67.5%, respectively (OR=2.576, 95% CI: 1.390-4.775, P<0.001), and the overall survival rates were 42.6% and 67.5%, respectively (OR=2.845, 95% CI: 1.549-5.225, P<0.001), with significant differences both. Conclusions: The primary indications for OE are malignant tumors of the conjunctiva and eyelids, with melanoma being the most common malignant tumor of the conjunctiva. Melanoma patients who undergo OE have a lower survival rate compared to other types of malignant tumors. Nevertheless, even in the presence of tumor lymph node metastasis, patients can achieve a relatively good prognosis through OE.


[Malignant degeneration in testicular feminization. Apropos of a case].
The authors describe the main therapeutic features found in a case of testicular feminisation that became malignant. Bilateral gonadal ablation should be carried out after puberty for fear of malignancy. When cancer occurs treatment is best decided on the grounds of extension to the lymph nodes and the histological findings in the tumour. Where there is no extension to the lymph nodes, surgery should be carried out on the gonads with radiotherapy to the lymph nodes. If the tumour is not clearly a seminoma the lymph nodes should be removed before radiotherapy is started.


Effect of a mobile-based educational app on blood pressure of patients with hypertension.
Hypertension is known as one of the most important non-communicable pervasive diseases. The purpose of the present study was to determine the effect of a mobile-based educational app on the blood pressure (BP) of patients with hypertension. This clinical trial was conducted on 66 military personnel who were definitively diagnosed with hypertension by a physician, and then assigned randomly into two groups as intervention (receiving mobile-based educational app) and control (receiving standard medical management but no app). Before the intervention, BP levels of both groups were measured with a calibrated sphygmomanometer. After 6 weeks, the BPs of both groups were remeasured using the same sphygmomanometer. Thereafter, descriptive and inferential statistics, including paired t-test, Mann-Whitney, Chi-square and Wilcoxon tests, were used. The data obtained were analysed using SPSS-21 software at a significance level of p<0.05. Comparison of the intervention and control groups showed no statistically significant difference between the groups in systolic BP (p=0.479) and diastolic BP (p=0.851) in the pre-intervention phase, but after the intervention, systolic and diastolic BP levels were significantly lower in the intervention group than in the control group (p=0.0001). The results suggested that the mobile-based educational app had a significant effect on reducing BP in patients with hypertension. Therefore, using this app is recommended for those military personnel with hypertension.


Dynamic regulation of brain aromatase and isotocin receptor gene expression depends on parenting status.
Fathering behavior is critical for offspring survival in many species across diverse taxa, but our understanding of the neuroendocrine mechanisms regulating paternal care is limited in part because of the few primarily paternal species among the common animal models. However, many teleosts display primarily paternal care, and among the teleosts, anemonefish species are particularly well suited for isolating molecular mechanisms of fathering as they perform parental care in isolation of many other typically competing behaviors such as territorial defense and nest building. The goal of this study was to determine the extent to which whole brain gene expression levels of isotocin receptors, arginine vasotocin receptors, and aromatase as well as circulating levels of the bioactive sex steroid hormones estradiol (E2) and 11-ketotestosterone (11KT) vary in association with parenting behavior in Amphiprion ocellaris. Brain aromatase and IT receptor gene expression were higher in both males and females that were parenting versus not. IT receptor expression was overall higher in males than females, which we interpret is a reflection of the greater parental effort that males display. Aromatase was overall higher in females than males, which we conclude is related to the higher circulating E2, which crosses into the brain and increases aromatase transcription. Results suggest both aromatase and IT receptors are dynamically upregulated in the brains of A. ocellaris males and females to support high levels of parental effort.


A quantitative theory of neural computation.
We show how a general quantitative theory of neural computation can be used to explain two recent experimental findings in neuroscience. The first of these findings is that in human medial temporal lobe there exist neurons that correspond to identifiable concepts, such as a particular actress. Further, even when such concepts are preselected by the experimenter, such neurons can be found with paradoxical ease, after examining relatively few neurons. We offer a quantitative computational explanation of this phenomenon, where apparently none existed before. Second, for the locust olfactory system estimates of the four parameters of neuron numbers, synapse numbers, synapse strengths, and the numbers of neurons that represent an odor are now available. We show here that these numbers are related as predicted by the general theory. More generally, we identify two useful regimes for neural computation with distinct ranges of these quantitative parameters.


Intrapsychic and Interpersonal Realms in Patients with Multiple Sclerosis and Their Comparison with Normal Individuals: A Look at Object Relations and Anger Management.
Objective: This study was designed to compare object relations and anger control between MS patients and normal individuals. Method : The present study was a cross-sectional case-control study with two groups: the case group (patients with MS) and the control group (normal controls without MS). 80 patients and 80 healthy individuals were selected according to the inclusion and exclusion criteria using a simple random sampling method. The research's data collection tool was a three-part questionnaire consisting of demographic information, the Bell Object Relations and the Reality Testing Inventory (BORRTI) and the State-Trait Anger Expression Inventory 2 (STAXI-2). The data were analyzed by the SPSS software version 26 using descriptive and analytical statistics (stepwise regression). Results: The results showed that in terms of object relations, there was no significant difference between the two groups except in alienation of relations (P = 0.035). The results also showed that in general, there was no statistically significant difference between the anger index of the group of MS patients and the normal controls. However, 12.8% of MS patients were significantly different in state of anger, trait anger and anger control compared to normal individuals. This difference was especially higher in angry temperament (P = 0.025) and the anger expression-in (P = 0.04). Conclusion: Although patients with MS were not significantly different from healthy individuals in terms of intrapsychic and interpersonal functions in the context of object relations and anger management, it seems that more complex and multifaceted explanations lie in the results that need further research.


Screening of Helicobacter pylori infection after gastrectomy for cancer or peptic ulcer: results of a cohort study.
Gastric cancer commonly follows a long-standing inflammation, mainly due to Helicobacter pylori (HP) infection. After resection, the stump develops precancerous alterations. Prospective study of patients undergoing endoscopy from April 1, 2000, through March 31, 2006. University departments of Surgery and Experimental Medicine and Pathology. One hundred eighty-seven patients receiving upper gastrointestinal tract endoscopy many years after surgery for duodenal ulcer or gastric cancer. Ten to 12 postoperative endoscopic biopsy samples were taken from the remnant stomach. The risk of gastric cancer precursor lesions associated with HP infection. The gastric cancer precursor lesions were more common in the entire HP-positive population (odds ratio [OR], 2.37; 95% confidence interval [CI], 1.25-4.49; P = .007). However, HP-positive patients undergoing resection for cancer had a higher risk of the precursor lesions compared with HP-negative patients in the same diagnostic group (OR, 4.20; 95% CI, 1.10-15.96) and all patients undergoing resection for duodenal ulcer (OR, 1.59; 95% CI, 0.44-5.73). The results of this investigation support the role of HP in gastric carcinogenesis and suggest that the HP eradication therapy might prevent the development of metachronous gastric cancer after gastric resection.


Multiple Procedure Payment Reduction: Health Policy Update.
Multiple Procedure Payment Reduction currently applies to multiple diagnostic imaging services administered to the same patient during the same day and entails a 50% decrease in the technical component and a 25% decrease in the professional component reimbursement. This might change with time due to further legislation, so it is important to be up-to-date on these health policy developments.


Implementation of a SVWP-based laser beam shaping technique for generation of 100-mJ-level picosecond pulses.
We present implementation of the energy-efficient and flexible laser beam shaping technique in a high-power and high-energy laser amplifier system. The beam shaping is based on a spatially variable wave plate (SVWP) fabricated by femtosecond laser nanostructuring of glass. We reshaped the initially Gaussian beam into a super-Gaussian (SG) of the 12th order with efficiency of about 50%. The 12th order of the SG beam provided the best compromise between large fill factor, low diffraction on the edges of the active media, and moderate intensity distribution modification during free-space propagation. We obtained 150 mJ pulses of 532 nm radiation. High-energy, pulse duration of 85 ps and the nearly flat-top spatial profile of the beam make it ideal for pumping optical parametric chirped pulse amplification systems.


Effects of long-term treatment with antipsychotics on serum leptin levels.
Abnormal regulation of the adipocyte-derived hormone leptin could play a role in body weight gain induced by antipsychotics. To study the effects of long-term antipsychotic treatment on leptin levels in patients with schizophrenia. Serum leptin levels were determined in 59 out-patients with chronic schizophrenia and in the same number of healthy subjects controlled by gender, age and body mass index. Leptin levels did not differ between patients and controls. Leptin levels in patients with schizophrenia correlated with weight gain, even after controlling for current weight, but did not show any association with clinical variables. Antipsychotic class tended to exert different effects over leptin levels (among atypicals, olanzapine induced a greater increase). Elevation of leptin levels induced by chronic antipsychotic treatment can be attributed to weight gain, but other mechanisms could be involved.


Clinical Complete Response of Recurrent Gastric Cancer after Third-line CPT-11 Chemotherapy.
A 75-year-old man underwent distal gastrectomy for advanced gastric cancer in September 2018. During the adjuvant chemotherapy, computed tomography (CT) revealed recurrence sites in the liver and para-aortic lymph nodes. Therefore, chemotherapy was initiated. After first-line (capecitabine with oxaliplatin) and second-line (paclitaxel with ramucirumab) treatments, nivolumab was used as third-line chemotherapy. This treatment showed a strong effect against the tumor. However, following an immune-related adverse effect (irAE) because of nivolumab, the therapy was halted. The irAE was diagnosed with central adrenal insufficiency that was controllable by oral intake of steroids. CPT-11 was started and showed a similarly strong effect to that observed for nivolumab. Eventually, the recurrent tumor lesions became too small to be detected by CT. We discontinued CPT-11 at the request of the patient. Even after discontinuation, no recurrent sites have been observed, allowing us to declare a case of clinical complete response (cCR). In conclusion, even if irAEs occur in a patient, continuing chemotherapy should be considered. However, if cCR is achieved, discontinuation of chemotherapy might be a strategic treatment option.


A pollen-specific polygalacturonase from lily is related to major grass pollen allergens.
A pollen-specific gene from lily (Lilium longiflorum Thunb. cv. Snow Queen), designated LLP-PG, was characterized. Southern blots of lily genomic DNA indicated that LLP-PG is a member of a small gene family. A thorough sequence analysis revealed that the LLP-PG gene is interrupted by two introns and encodes a protein of 413 amino acids, with a calculated molecular mass of 44 kDa, and a pI of 8.1. Evaluation of the hydropathy profile showed that the protein has a hydrophobic segment at the N-terminus, indicating the presence of a putative signal peptide. A sequence similarity search showed a significant homology of the encoded protein to pollen polygalacturonases (PGs) from various plant species and to an important group (group 13) of grass pollen allergens. The LLP-PG transcript is pollen-specific and it accumulates only at the latest stage during pollen development, in the mature pollen. In contrast to other "late genes" LLP-PG transcript can neither be induced by abscisic acid (ABA) nor by dehydration. Immunoblot analyses of pollen protein extracts from lily, timothy grass and tobacco with IgG antibodies directed against LLP-PG and against the timothy grass pollen allergen, Phl p 13, indicated that lily LLP-PG shares surface-exposed epitopes with pollen PGs from monocotyledonous and dicotyledonous plants. Enzyme-linked immunosorbent assay (ELISA) analyses and inhibition ELISA assays with patients' IgE demonstrated a very low IgE reactivity of lily rLLP-PG and a lack of cross-reactivity between rLLP-PG and the timothy grass pollen allergen, rPhl p 13. These data demonstrated that despite the significant sequence homology and the conserved surface-exposed epitopes LLP-PG represents a low-allergenic member of pollen PGs.


Administrator turnover and quality of care in nursing homes.
In this article, I examine the association between turnover of nursing home administrators and five important quality of care outcomes. The data came from a survey of 420 nursing facilities and the 1999 On-line Survey, Certification, and Reporting System. Using multivariate logistic regression analyses, I looked at the effects of turnover of administrators in nursing homes belonging to chain organizations and in nursing homes not belonging to chain organizations. I found the average annual turnover rate of administrators to be 43%. The multivariate logistic regression analyses show that in nursing homes belonging to chains, administrator turnover is associated with a higher than average proportion of residents who were catheterized, had pressure ulcers, and were given psychoactive drugs and with a higher than average number of quality-of-care deficiencies. In nursing homes not belonging to chains I found that turnover of administrators is associated with a higher than average proportion of residents who were restrained, were catheterized, had pressure ulcers, and were given psychoactive drugs. There is a need to improve understanding of how and why better outcomes are achieved in some nursing homes. This investigation serves to focus attention on nursing home administrators. I believe this study provides preliminary evidence that the turnover of administrators may have an important association with quality of care in nursing homes.


The changing phases of pandemic (H1N1) 2009 in Queensland: an overview of public health actions and epidemiology.
A graded public health response was implemented to control the pandemic (H1N1) 2009 outbreak in Queensland. Public health measures to contain the outbreak included border control, enhanced surveillance, management of cases and contacts with isolation or quarantine and antivirals, school closures and public education messages. The first confirmed case in Australia was notified on 8 May 2009, in a traveller returning to Queensland from the United States. In Queensland, 593 laboratory-confirmed cases were notified with a date of onset between 26 April and 22 June 2009, when the Protect phase of the Australian Health Management Plan for Pandemic Influenza was implemented; 16 hospitalisations and no deaths were reported during this time. The largest number of confirmed cases was reported in the 10-19-years age group (167, 28% of cases), followed by the 20-29-years age group (153, 26% of cases). With ongoing community transmission, the focus has shifted from public health to the clinical domain, with an emphasis on protecting vulnerable groups. Considerable resources have been invested to prevent and control the spread of disease in Indigenous communities in Far North Queensland. The capacity of clinical services to cope with increased admissions, the potential for widespread antiviral resistance, and rollout of mass vaccination campaigns remain future challenges.


[Determination of antibodies to Streptococcus group A polysaccharide by an immunodiffusion method in human sera in various pathological processes of streptococcal etiology].
A method for the assay of antibodies to the specific antigenic determinant of group A streptococcal polysaccharide (A-polysaccharide) in human sera was developed. The sera were tested in the precipitation test in agar gel with different doses of A-polysaccharide. The presence of a high level of the above-mentioned antibodies is indicative of infection caused by group A streptococcus, but not streptococci of other groups or by the L-forms of streptococci. In 87.5% of patients with primary rheumatism a high level of antibodies to the specific antigenic determinant of A-polysaccharide was detected during the first day of the disease, which confirms most convincingly the etiological role of group A streptococcus in rheumatism. Considerable differences in the level of antibodies to A-polysaccharide in the active and non-active phases of rheumatism have been established, which makes it possible to use the presence of a high level of these antibodies as an indicator of the rheumatic process activity. A considerable percentage of sera with a high level of antibodies to A-polysaccharide was also detected in erysipelas and acute glomerulonephritis patients.


Increased plasma concentrations of anterior gradient 2 protein are positively associated with ovarian cancer.
Ovarian cancer is often asymptomatic and is diagnosed at an advanced stage with poor survival rates, thus there is an urgent need to develop biomarkers for earlier detection of ovarian cancer. In the present study, we demonstrate for the first time that the previously reported metastasis-inducing protein AGR2 (anterior gradient protein 2) can be detected in the blood of ovarian cancer patients. Using a newly developed ELISA, we show significantly increased concentrations of AGR2 protein in plasma from cancer patients relative to normal controls. Plasma AGR2 concentrations were highest in stages II and III ovarian cancer patients and were similarly elevated in patients with both serous and non-serous tumours. The identification of elevated plasma concentrations of AGR2 may provide a useful biomarker to aid in the discrimination of normal and ovarian cancer patients particularly when used in combination with CA125.


Restless legs syndrome in patients infected with Helicobacter pylori.
Objective Although the etiology of restless legs syndrome (RLS) is yet to be discovered, some studies have mentioned the effect of infectious diseases in occurrence of RLS. This study aims to determine the association between common Helicobacter pylori (H. pylori) infection and occurrence of RLS. Methods In this descriptive analytical cross-sectional study, patients with RLS who were referred to the Internal Medicine Clinic of Fayazbakhsh Hospital in Tehran from September to December 2016 were evaluated. Patients with underlying diseases that would lead to secondary RLS were excluded from the study. The control group were matched with the patients group regarding their age and gender, but did not have RLS or diseases that would lead to secondary RLS. All participants underwent serologic tests for evaluating serum levels of IgA and IgG antibodies against H. pylori. Data were analyzed using Chi-Square test and Logistic Regression with SPSS Software Version 20. The significance level was ≤0.05. Results Fifty-seven RLS patients and 64 healthy controls were included in the study. In the RLS group, 36 participants (29.8%) had H. pylori infection. This number was 27 participants (22.3%) in the control group. Data analysis using logistic regression showed a significant relation between H. pylori and occurrence of RLS (p value ≤ 0.05). Conclusions Results of the present study indicated that infection with H. pylori is related with the occurrence of RLS. It seems that releasing inflammatory factors, iron deficiency, and small intestinal bacterial overgrowth are some of the involved mechanisms in this pathogenesis.


Induction of the pi class of glutathione S-transferase by carnosic acid in rat Clone 9 cells via the p38/Nrf2 pathway.
Induction of phase II enzymes is important in cancer chemoprevention. We compared the effect of rosemary diterpenes on the expression of the pi class of glutathione S-transferase (GSTP) in rat liver Clone 9 cells and the signaling pathways involved. Culturing cells with 1, 5, 10, or 20 μM carnosic acid (CA) or carnosol (CS) for 24 h in a dose-dependent manner increased the GSTP expression. CA was more potent than CS. The RNA level and the enzyme activity of GSTP were also enhanced by CA treatment. Treatment with 10 μM CA highly induced the reporter activity of the enhancer element GPEI. Furthermore, CA markedly increased the translocation of nuclear factor erythroid-2 related factor 2 (Nrf2) from the cytosol to the nucleus after 30 to 60 min. CA the stimulated the protein induction of p38, nuclear Nrf2, and GSTP was diminished in the presence of SB203580 (a p38 inhibitor). In addition, SB203580 pretreatment or silencing of Nrf2 by siRNA suppressed the CA-induced GPEI-DNA binding activity and GSTP protein expression. Knockdown of p38 or Nrf2 by siRNA abolished the activation of p38 and Nrf2 as well as the protein induction and enzyme activity of GSTP by CA. These results suggest that CA up-regulates the expression and enzyme activity of GSTP via the p38/Nrf2/GPEI pathway.


Natural fertility, infertility and the role of medically assisted reproduction: The knowledge amongst women of reproductive age in North Queensland.
The demand for medically assisted reproduction continues to increase, with more women encountering challenges with fertility. Due to misconceptions and gaps in knowledge, women are often unaware of the risks related to delayed childbearing. Lack of understanding of natural fertility, infertility and the role of medically assisted reproduction can lead to emotional suffering and changes in family plans. To assess the understanding and knowledge that women of reproductive age in North Queensland have regarding natural fertility, infertility and the role of medically assisted reproduction. Data were collected from 120 women (30 nurses, 30 teachers, 30 university students and 30 Technical and Further Education students) via the distribution of a structured questionnaire. Participants were surveyed in person about their personal plans and opinions, knowledge about natural fertility, infertility and medically assisted reproduction, and their preferred source of information. Participants demonstrated suboptimal knowledge levels throughout all sections of the questionnaire, in particular when asked about medically assisted reproduction. When asked to identify their main source of information, 'friends and family' was the most popular choice. Results from this North Queensland study add to the existing international literature, highlighting the widespread nature of the problem. Without adequate understanding of natural fertility, the risks of infertility, and the role and limitations of medically assisted reproduction, women make uninformed decisions. Development of local reproductive health education programs need to be instigated in response.


The conserved methionine residue of the metzincins: a site-directed mutagenesis study.
The metalloprotease clan of the metzincins derive their name from the presence of a conserved methionine residue that is located on the C-terminal side of the zinc-binding consensus sequence HEXXHXXGXXH. This methionine residue is located in a rather divergent part of the primary sequence but is structurally very well conserved. It is located under the pyramidal base of the three histidine residues that coordinate the catalytic zinc ion and is not involved in any direct contact with the metal nor the substrate. In order to clarify its role, this methionine residue (M226) of the protease C from Erwinia chrysanthemi has been mutated to various other amino acids. The mutants M226L, M226A, M226I were sufficiently stable to be isolated, while the mutants M226H, M226S and M226N could not be purified. The kinetic properties of these mutants were analysed. All mutants showed decreased activity, whereby increases in K(M) as well as decreases in k(cat) were observed. The M226L mutant and M226C-E189 K double mutant, which has the catalytic glutamic acid substituted as well, could be crystallised. The structure of the M226L mutant was determined to a resolution of 2.0 A and refined to R(free) of 0.20. The structure is isomorphous to the wild-type and does not show large differences, with the exception of a very small movement of the zinc-liganding histidine residues. The M226C-E189 K double mutant crystal structure has been refined to an R(free) of 0.20 at 2.1 A resolution. A small rearrangement of the zinc-liganding histidine residues can be detected, which leads to a slightly different zinc coordination and could explain the decrease in activity.


Antibody in cattle experimentally infected with contagious bovine pleuropneumonia.
Antibody responses in cattle experimentally infected with contagious bovine pleuropneumonia were assayed by the complement fixation (CF), plate agglutination (PA), and agar-gel diffusion precipitin (AGDP) tests. Sera were also fractionated by sucrose gradient centrifugation, by chromatography on diethylaminoethyl (DEAE)-cellulose columns, and by starch-block electrophoresis. Serum fractions were assayed for antibody by the CF and PA tests. Antibody was detected by the CF and PA tests from 7 days postinoculation (DPI) throughout the test period of 154 days. The AGDP test was the least sensitive and was negative after 28 DPI. By sucrose gradient centrifugal analysis, only 19S antibody could be detected in the 7 DPI sera, but 19 and 7S antibodies were found in the 14, 21, 28, 35, and 42 DPI sera. Only 7S antibody was found in sera subsequently collected until 154 DPI at the conclusion of the experiment. Results of chromatographic fractionation of sera on DEAE-cellulose columns showed that most of the CF antibody was adsorbed when 0.0175 m phosphate buffer (pH 6.3) was used for elution of proteins. Plate agglutination antibody activity was found in both immunoglobulin (Ig)G and IgM fractions from 7 to 42 DPI and only in the IgG fraction thereafter. By starch-block electrophoresis, the 14 DPI antibody was of beta mobility (IgM), whereas at 21 DPI the antibody mobility was gamma-beta. In the 28 and later DPI sera, CF antibody had gamma mobility.


The Association of Maternal Asthma and Early Pregnancy Vitamin D with Risk of Preeclampsia: An Observation From Vitamin D Antenatal Asthma Reduction Trial (VDAART).
Maternal asthma, uncontrolled asthma, and low vitamin D levels during pregnancy have been individually linked to increased risk of preeclampsia. To investigate the association of history of physician-diagnosed asthma and uncontrolled asthma status during pregnancy with the risk of preeclampsia and the effects of early pregnancy vitamin D concentrations on this relationship. A total of 816 subjects with available pregnancy outcome data and risk factors of interest were analyzed. A group of experienced obstetricians and gynecologists from 3 study centers validated the preeclampsia diagnoses. Vitamin D was measured using the DiaSorin method at 10 to 18 weeks of gestation. The Pregnancy-Asthma Control Test was used to assess asthma control during pregnancy. Criterion-based stepwise variable selection algorithm was applied to investigate the relationships of risk factors of interest (history of asthma diagnosis, uncontrolled asthma during pregnancy, and vitamin D) to preeclampsia. The incidence of preeclampsia was not related to the presence of asthma diagnosis (8.9% with vs 7.4% without). The adjusted odds of preeclampsia controlled for maternal serum 25-hydroxyvitamin D (25OHD) concentrations was higher for women with a higher proportion of uncontrolled asthma months per visit during pregnancy (adjusted odds ratio, 3.55; 95% CI, 1.15-13.0). Adjusting for asthma control status during pregnancy, an additional decrease in the associated preeclampsia risk by 7% was observed for a 10-unit (ng/mL) increase in early pregnancy 25OHD levels (adjusted odds ratio10-unit, 0.60; 95% CI, 0.43-0.82) as compared with the previous risk estimate of preeclampsia associated with low maternal 25OHD unadjusted for asthma control status. Uncontrolled asthma during pregnancy is associated with an increased risk of preeclampsia. Early pregnancy 25OHD contributes to the association of uncontrolled asthma status with preeclampsia.


Determination of pseudocholinesterase activity in the gingival crevicular fluid, saliva, and serum from patients with juvenile periodontitis and rapidly progressive periodontitis.
By use of a spectrophotometric method, pseudocholinesterase (PCE) activities were determined in gingival crevicular fluid (GCF), saliva, and serum from patients with juvenile periodontitis (JP) and rapidly progressive periodontitis (RPP) and from controls. The PCE activity in the GCF samples was 181 +/- 48 U/L in the JP group, 588 +/- 135 U/L in the RPP group, and 88.5 +/- 29.1 U/L in the control group. Saliva PCE activity levels were 9.1 +/- 1.7 U/L in the JP group, 21.8 +/- 4.5 U/L in the RPP group, and 12.7 +/- 0.8 U/L in the control group. GCF contained a higher PCE activity than saliva but a lower one than that of serum. The RPP group had a significantly higher PCE activity in both the GCF and saliva samples. No significant differences could be found regarding serum enzyme levels. Also, no significant correlations were present between biochemical values and the severity of periodontal disease. GCF may be an important source for the PCE content of saliva. It is suggested that the increased PCE activity seen in RPP patients might be caused by either the direct production of esterases by bacteria or the induction of esterases during periodontal destruction.


Spongy titanosilicate promotes the catalytic performance and reusability of WO3 in oxidative cleavage of methyl oleate.
A tungsten containing catalyst catalyzed oxidative cleavage of methyl oleate (MO) by employing H2O2 as an oxidant and is known as an efficient approach for preparing high value-added chemicals, however, the tungsten leaching problem remains unresolved. In this work, a binary catalyst consisting of tungsten oxide (WO3) and spongy titanosilicate (STS) zeolite is proposed for MO oxidative cleavage. The function of STS in this catalyst is investigated. On the one hand, STS converts MO to 9,10-epoxystearate (MES), which further forms nonyl aldehyde (NA) and methyl azelaaldehydate (MAA) with the catalysis of WO3. In this way, MO oxidation and hydrolysis that generates unwanted diol product 9,10-dihydroxystearate (MDS) decreases obviously. On the other hand, STS decomposes peroxide and promotes the conversion of soluble peroxotungstate to insoluble polytungstate. Meanwhile, these tungsten species are allowed to precipitate on its surface instead of remaining in the liquid phase owing to its relative large specific area. Therefore, tungsten leaching can be reduced from 37.0% to 1.2%. Due to the cooperation of WO3 and STS, 94.4% MO conversion and oxidative cleavage product selectivity of 63.1% are achieved, and the WO3-STS binary catalyst maintains excellent catalytic performance for 8 recycling reactions.


Multifunctional Vesicles from a Self-assembled Cluster-Containing Diblock Copolymer.
We describe a new diblock copolymer composed of two segments with complementary functionalities. One block contains pendent photo-cross-linkable cinnamoyl groups, and the other contains molecular clusters, Co6Se8, capable of multielectron redox processes. This multifunctional macromolecule is synthesized by sequential ring-opening metathesis polymerization of monomers constructed using norbornene moieties. Remarkably, the tethered molecular cluster gives access to three different charge states in N, N-dimethylformamide: neutral, +1, and +2. In tetrahydrofuran, by contrast, the charged copolymer self-assembles into vesicles that inhibit the redox reactions. The wall of these vesicles can be cross-linked by exploiting the photoinduced 2 + 2 cycloaddition of the cinnamoyls to form cyclobutane dimers. Moreover, these vesicles can be loaded with molecular cargo and used as cross-linkable containers; we demonstrate this feature by encapsulating the molecular dye methylene blue into the capsules. Our work is the first report of a well-defined block copolymer containing a metal chalcogenide molecular cluster; more generally, it opens the door to new applications of metal-containing polymers.


How to differentiate skin rash in covid, mononucleosis, chickenpox, sixth disease and measles.
Skin rashes seen during COVID-19 usually feature maculopapular or vesicular morphology, thus mimicking cutaneous eruptions occurring in other common infectious dermatoses, such as mononucleosis, chickenpox, sixth disease and measles, with possible diagnostic mistakes. In this review article, we sought to provide a practical overview about clinical appearance of skin rashes related to SARS-CoV-2 infection. The study summarizes literature evidence on clinical patterns of COVID-19-associated maculopapular or vesicular rash, with a particular emphasis on the principal points of differentiation with possible mimickers. Several differences do exist between rashes due to SARS-CoV-2 infection and other viral eruptions, mainly including lesions morphology, spreading pattern, symptoms and mucosal involvement. The increase of awareness of such features among clinicians may help promptly recognize COVID-19-related exanthemas in order to take proper action to manage the infection.


Interferon-associated retinopathy in a uniform regimen of natural interferon-alpha therapy for chronic hepatitis C.
The development of retinal lesions induced by a uniform regimen of interferon-alpha therapy for chronic hepatitis C was prospectively investigated. Eighty-one patients received 6 mega units of natural interferon-alpha intramuscularly daily for 2 weeks and then 3 times a week for 22 weeks. The total dose of interferon-alpha administered was uniformly 478 mega units per patient. Two expert ophthalmologists prospectively examined the patients for retinal lesions before, during and after the therapy. Retinopathy was not found in comparison groups or any of the patients before treatment. In total 34.6% (28/81) of the patients showed cotton-wool spots or minor retinal hemorrhage, or both lesions, during therapy, but these lesions were reversed during or after interferon therapy. The occurrence rates of cotton-wool spots alone, retinal hemorrhage alone and both lesions were 13.6% (11/81), 6.2% (5/81), and 14.8% (12/81), respectively. The appearance of retinopathy did not correlate with patients' background including viral loads and response to the therapy, but was more frequently found in older patients and patients with hypertension and/or diabetes mellitus; disappearance of retinopathy was more prolonged than in patients without these complications. Almost all the lesions appeared 2-4 months after the start of the therapy, and the severity of the lesions did not differ between patients with and without hypertension and/or diabetes mellitus. Although it is not clear if interferon-associated retinopathy occurs in a dose-dependent manner, the present study shows a standard pattern of the occurrence of retinopathy in patients with chronic hepatitis C receiving a uniform dosage of natural interferon-alpha.


Inheritance of organelle DNA markers in a pea cross associated with nuclear-cytoplasmic incompatibility.
An unusual biparental mode of plastid inheritance was found in pea, in a cross associated with nuclear-cytoplasmic incompatibility manifested as deficiency of chlorophyll pigmentation. Plastid DNA marker trnK and mitochondrial DNA marker cox1 were analyzed in F1 progeny that received cytoplasm from an accession of a wild subspecies Pisum sativum ssp. elatius. Plants with sectors of green tissue on leaves and seed cotyledons with green patches on an otherwise chlorotic background were found to carry paternally inherited plastid DNA, suggesting that photosynthetic function was affected by nuclear-cytoplasmic conflict and required proliferation of paternally inherited plastids for normal performance. The paternally inherited plastid DNA marker was also observed in the roots. The presence of the paternal marker in cotyledons, roots and leaves was independent of each other. Inheritance of the mitochondrial DNA marker cox1 appeared to be of the maternal type.


Graphene composite structure based optical absorption pressure sensor.
In this paper, a graphene composite structure based optical absorption pressure sensor is proposed. First, a composite structure which is composed of PDMS micro-pyramid structure, graphene film, and waveguide is introduced. The sensitive mechanism and dynamic working state of the pressure sensor are analyzed continuously. Second, the mapping between the pressure on PDMS and its contact area with the graphene film is deeply analyzed, as well as the optical transmission properties of graphene combined with waveguides, followed by a series of simulations about the optical power output performance facing different pressure conditions. Finally, the designed sensor samples are prepared and a series of performance verification experiments were carried out. The experimental results show that the range of the pressure sensor is 0-870kPa. The sensitivity in the pressure range of 0-100kPa is 2.83×10-1µW/kPa. The experimental results effectively prove that the designed graphene composite structure based optical absorption pressure sensor has high sensitivity and good repeatability, which further verifies the feasibility of the design and analysis method.


Design, semi-synthesis and examination of new gypsogenin derivatives against leukemia via Abl tyrosine kinase inhibition and apoptosis induction.
Chronic myelogenous leukemia (CML) is characterized by Philadelphia translocation arising from Bcr-Abl fusion gene, which encodes abnormal oncoprotein showing tyrosine kinase (TK) function. Certain mutations in kinase domain, off-target effects and resistance problems of current TK inhibitors require the discovery of novel Abl TK inhibitors. For this purpose, herein, we synthesized new gypsogenin derivatives (6a-l) and evaluated their anticancer effects towards CML cells along with healthy cell line and different leukemic cells. Among these compounds, compound 6l was found as the most active anti-leukemic agent against K562 CML cells compared to imatinib exerting less cytotoxicity towards PBMCs (healthy). This compound also revealed significant anti-leukemic effects against Jurkat cell line. Besides, compound 6l enhanced apoptosis in CML cells with 52.4 % when compared with imatinib (61.8 %) and inhibited Abl TK significantly with an IC50 value of 13.04 ± 2.48 μM in a large panel of kinases accentuating Abl TK-mediated apoptosis of compound 6l in CML cells. Molecular docking outcomes showed that compound 6l formed mainly crucial interactions in the ATP-binding cleft of Abl TK similar to that of imatinib. Ultimately, in silico pharmacokinetic evaluation of compound 6l indicated that this compound was endowed with anti-leukemic drug candidate features.


High performance asymmetric supercapacitors based on Ti3C2T x MXene and electrodeposited spinel NiCo2S4 nanostructures.
Spinel metal sulfides have been investigated for a wide range of applications mostly in electrochemical energy storage owing to their better electronic conductivity and high reversible redox activity. Herein, we report a facile fabrication approach for the binder-free supercapacitor electrodes based on spinel NiCo2S4 (NCS) on various substrates such as Cu-foil (CF), Ni-foam (NF), and vertical graphene nanosheets grown on carbon tape (VG) via a single step-controlled electrodeposition technique. The obtained electrodeposited NiCo2S4 grown on Cu-foil (denoted as CF-NCS) in symmetric assembly shows a high specific capacitance of 167.28 F g-1 compared to NCS grown on Ni-foam and VG substrates, whereas, symmetric NiCo2S4 grown on a VG substrate device exhibits better cycling performance (81% for 3000 cycles) compared to CF-NCS and NF-NCS. Furthermore, an asymmetric supercapacitor was assembled in combination with MXene (Ti3C2T x ) as a negative electrode (denoted as TCX). As a result, the CF-NCS//TCX device exhibits a high areal capacitance of 48.6 mF cm-2 at 2 mA cm-2 of current density. We also report good specific capacitance of 54.57 F g-1 at 2 A g-1; in addition, the CF-NCS//TCX assembly delivers maximum areal and gravimetric energy density of 14.86 mWh cm-2 and 14.86 Wh kg-1 respectively. In contrast, the VG-NCS//TCX device showed improved cycling stability with 85% of capacitance retention over 5000 cycles owing to its highly porous structure and multiple conductive networks in the VG substrate and provides structural stability to NCS with fast ion diffusion. This experiment favors 2D MXene as a capacitive electrode that provides a replacement for carbon-based electrodes in asymmetric assembly with superior electrochemical performance. Hence, the hierarchical NCS structure grown on the various substrates in combination with MXene serve as a promising material for energy storage application.


Fabrication of highly uniform nanoparticles from recombinant silk-elastin-like protein polymers for therapeutic agent delivery.
Here we generate silk-elastin-like protein (SELP) polymeric nanoparticles and demonstrate precise control over their dimensions using an electrospray differential mobility analyzer (ES-DMA). Electrospray produces droplets encompassing several polymer strands. Evaporation ensues, leading polymer strands to accumulate at the droplet interface, forming a hollow nanoparticle. The resulting nanoparticle size distributions, which govern particle yield, depend on buffer concentration to the -1/3 power, polymer concentration to the 1/3 power, and ratio of silk-to-elastin blocks. Three recombinantly tuned ratios of 8:16, 4:8, and 4:16, respectively named SELP-815K, SELP-47K, and SELP-415K, are employed, with the latter ratio resulting in a thinner shell and larger diameter for the nanoparticles than the former. The DMA narrows the size distribution by electrostatically classifying the aerosolized nanoparticles. These highly uniform nanoparticles have variations of 1.2 and 1.4 nm for 24.0 and 36.0 nm particles, respectively. Transmission electron microscopy reveals the nanoparticles to be faceted, as a buckling instability releases compression energy arising from evaporation after the shell has formed by bending it. A thermodynamic equilibrium exists between compression and bending energies, where the facet length is half the particle diameter, in agreement with experiments. Rod-like particles also formed from polymer-stabilized filaments when the viscous length exceeds the jet radius at higher solution viscosities. The unusual uniformity in composition and dimension indicates the potential of these nanoparticles to deliver bioactive and imaging agents.


Evaluating the potential of fluorinated tyrosines as spectroscopic probes of local protein environments: a UV resonance Raman study.
Ultraviolet resonance Raman (UVRR) studies designed to test the utility of fluorinated tyrosines as spectroscopic probes of the local environment are presented. Specifically, resonance Raman spectra of 2-fluoro-L-tyrosine and 3-fluoro-L-tyrosine (3-Y(f)) obtained with 229 nm excitation are reported. In contrast to the modest environmental dependence of the tyrosine resonance Raman spectrum, the spectrum of 3-Y(f) is found to be extremely dependent on the hydrogen bonding strength of the surrounding environment. Preliminary ab initio studies suggest that this behavior is due to normal modes having dominant contributions from the C-OH and C-F internal coordinates. Hydrogen bonding to the solvent perturbs the internal coordinate energetics and/or couplings, thereby altering the character of the normal modes and the corresponding transition frequencies and/or intensities. In addition to the solvent studies, 3-Y(f) is site specifically incorporated into the influenza hemagglutinin (HA) 100-107 peptide which binds to the Fv fragment of the 17/9 anti-HA(98-108) peptide antibody. These studies demonstrate that the spectrum of 3-Y(f) can be monitored in the presence of native tyrosine. In summary, the studies presented here demonstrate that 3-Y(f) holds exceptional promise as a probe of the protein environment.


Gastroretentive drug delivery systems.
A controlled drug delivery system with prolonged residence time in the stomach is of particular interest for drugs that i) are locally active in the stomach, ii) have an absorption window in the stomach or in the upper small intestine, iii) are unstable in the intestinal or colonic environment, or iv) exhibit low solubility at high pH values. This article gives an overview of the parameters affecting gastric emptying in humans as well as on the main concepts used to design pharmaceutical dosage forms with prolonged gastric residence times. In particular, bioadhesive, size-increasing and floating drug delivery systems are presented and their major advantages and shortcomings are discussed. Both single- and multiple-unit dosage forms are reviewed and, if available, results from in vivo trials are reported.


Neisseria meningitidis in the anal canal of homosexual men.
Cultures were obtained from the oropharynx, urethra, and anal canal of 157 homosexual men. Neisseria gonorrhoeae was identified in 30 men (19.1%), Neisseria meningitidis in 32 men (20.4%), and Neisseria lactamicus and Branhamella catarrhalis in one man each. N. gonorrhoeae was isolated from the anal canal of three men (1.9%), and N. meninititidis was identified in the anal canal of seven men (4.5%). These findings suggest that confirmatory tests are indicated for homosexual males with rectal isolates presumptively identified as N. gonorrhoeae.


Cutaneous and medullar gnathostomiasis in travelers to Mexico and Thailand.
Gnathostomiasis is a rare nematode disease acquired by travelers to endemic areas. The most common clinical presentations are cutaneous forms; however, neurologic involvement can also occur. We present two cases of gnathostomiasis, one of them with severe neurologic complications, in Spanish travelers to Thailand and Mexico, who consumed local food and became infected.


Specificity of the weak binding between the phage SPO1 transcription-inhibitory protein, TF1, and SPO1 DNA.
The interaction of the phage SPO1 protein transcription factor 1 (TF1), with DNA has been analyzed by membrane filter binding and by sedimentation methods. Substantially specific binding of TF1 to helical SPO1 DNA can be demonstrated by nitrocellulose filter-binding assays at relatively low ionic strength (0.08). However, TF1-DNA complexes dissociate and reequilibrate relatively rapidly and this makes filter-binding assays unsuitable for quantitative measurements of binding equilibra. Accordingly, the sedimentation properties of TF1-DNA complexes have been explored and a short-column centrifugation assay has been elaborated for quantitative measurements. Preferential binding of TF1 to the hydroxymethyluracil-containing SPO1 DNA has also been demonstrated by short-column centrifugation. TF1 binds relatively weakly and somewhat cooperatively to SPO1 DNA at many sites; TF1-DNA complexes dissociate and reequilibrate rapidly. At 20 degrees C in 0.01 M phosphate, pH 7.5, 0.15 KC1, one molecule of TF1 can bind to approximately every 60 nucleotide pairs of SPO1 DNA.


Quantifying the phenotype in autism spectrum disorders.
Twin and family studies suggest that familial transmission in autism extends to a spectrum of social and behavioral deficits that characterize individuals who have significant impairments within the autism spectrum, but do not meet formal criteria for autistic disorder. Standardized diagnostic instruments, including the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS-WPS Edition), offer the opportunity to quantify deficits across the autism spectrum, controlling effects of language and cognitive delay, in individuals with significant impairments. It is suggested that quantitative measures of social reciprocity and repetitive behaviors and interests, with separate quantification of expressive language level and nonverbal intelligence, most accurately reflect the range of behavioral phenotypes in autism spectrum disorders.


Estimating skills level in recreational skiing: Development and validation of a practical multidimensional instrument.
Skiing and snowboarding are both popular recreational alpine sports, with substantial injury risk of variable severity. Although skills level has repeatedly been associated with injury risk, a validated measure to accurately estimate the actual skills level without objective assessment is missing. This study aimed to develop a practical validated instrument, to better estimate the actual skills level of recreational skiers, based on the criteria of the Dutch Skiing Federation (DSF), and covering five different skill domains. A sample of Dutch recreational skiers (n = 84) was asked to fill in a questionnaire reflecting seven, a priori chosen predictors by expert opinion, to ski downhill and to be objectively evaluated by expert assessors. The instrument was developed to have a multidimensional character and was validated according to the TRIPOD guideline (Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis). The sample reported an overall incorrect self-reported estimation of their skills, compared with the observed skill score. The instrument showed good calibration and underwent multiple validation methods. The estimated skills score showed to be closer to the observed scores, than self-reportage. Our study provides a practical, multidimensional, and validated instrument to estimate the actual skills level. It proved to better reflect the actual skills levels compared with self-reportage among recreational skiers.


RNA-Seq analysis of global transcriptomic changes suggests a roles for the MAPK pathway and carbon metabolism in cell wall maintenance in a Saccharomyces cerevisiae FKS1 mutant.
FKS1 encodes a β-1,3-glucan synthase, which is a key player in cell wall assembly in Saccharomyces cerevisiae. Here we analyzed the global transcriptomic changes in the FKS1 mutant to establish a correlation between the changes in the cell wall of the FKS1 mutant and the molecular mechanism of cell wall maintenance. These transcriptomic profiles showed that there are 1151 differentially expressed genes (DEGs) in the FKS1 mutant. Through KEGG pathway analysis of the DEGs, the MAPK pathway and seven pathways involved in carbon metabolism were significantly enriched. We found that the MAPK pathway is activated for FKS1 mutant survival and the synthesis of cell wall components are reinforced in the FKS1 mutant. Our results confirm that the FKS1 mutant has a β-1,3-glucan defect that affects the cell wall and partly elucidate the molecular mechanism responsible for cell wall synthesis. Our greater understanding of these mechanisms helps to explain how the FKS1 mutant survives, has useful implications for the study of similar pathways in other fungi, and increases the theoretical foundation for the regulation of the cell wall in S. cerevisiae.


Analysis of the interaction between hPFTAIRE1 and PLZF in a yeast two-hybrid system.
hPFTAIRE1 is a Cdc2-related kinase family member. To search its substrates and regulatory proteins, hPFTAIRE1 was fused to LexA and used as a bait to screen a human brain LexA two-hybrid library. In this screening, seven hPFTAIRE1 interacting proteins, including promyelocytic leukemia zinc finger (PLZF), were obtained. The interaction between PLZF and hPFTAIRE1 was confirmed by beta-galactosidase assay and Leu growth activity. PLZF encodes a transcription factor belonging to the POZ/BTB domain and Krüpel zinc finger (POK) family. The highly conserved POZ/BTB domain plays a critical role in protein-protein interaction. We deleted the POZ/BTB and Krüpel zinc finger domains, respectively, and observed the interaction between hPFTAIRE1 and truncated PLZFs by liquid beta-galactosidase activity assay. A weak interaction was detected between hPFTAIRE1 and PLZF. We also observed the interaction between PLZF and another Cdc2-related kinase, PCTAIRE1. A similar result was observed. The interaction between PLZF and hPFTAIRE1 or PCTAIRE1 was confirmed by co-immunoprecipitation assay in a yeast system. PLZF is a phosphoprotein and plays multiple roles during cell growth. Our results suggest that hPFTAIRE1 and PCTAIRE1 may play important roles in the functional regulation of PLZF.


A Dry Powder Platform for Nose-to-Brain Delivery of Dexamethasone: Formulation Development and Nasal Deposition Studies.
Nasal route of administration offers a unique opportunity of brain targeted drug delivery via olfactory and trigeminal pathway, providing effective CNS concentrations at lower doses and lower risk for adverse reactions compared to systemic drug administration. Therefore, it has been recently proposed as a route of choice for glucocorticoids to control neuroinflammation processes in patients with severe Covid-19. However, appropriate delivery systems tailored to enhance their efficacy yet need to emerge. In this work we present the development of sprayable brain targeting powder delivery platform of dexamethasone sodium phosphate (DSP). DSP-loaded microspheres, optimised employing Quality-by-Design approach, were blended with soluble inert carriers (mannitol or lactose monohydrate). Powder blends were characterized in terms of homogeneity, flow properties, sprayability, in vitro biocompatibility, permeability and mucoadhesion. Nasal deposition studies were performed using 3D printed nasal cavity model. Mannitol provided better powder blend flow properties compared to lactose. Microspheres blended with mannitol retained or enlarged their mucoadhesive properties and enhanced DSP permeability across epithelial model barrier. DSP dose fraction deposited in the olfactory region reached 17.0% revealing the potential of developed powder platform for targeted olfactory delivery. The observed impact of nasal cavity asymmetry highlighted the importance of individual approach when aiming olfactory region.


Correlation Between C3435T Locus of ABCB1 Gene and Poststroke Depression in China.
This study aims to investigate whether a relationship exists between the C3435T polymorphism of ABCB1 gene and poststroke depression (PSD). A total of 82 PSD patients and 115 nondepression patient (NPSD) controls were included in this study. All patients were evaluated using the Hamilton Rating Scale for Depression to determine the severity of depression and complete the packet. PSD patients were diagnosed in accordance with the DSM-V criteria. The C3435T polymorphism of ABCB1 was genotyped through fluorescence in situ hybridization and chromosome karyotype analysis system. The PSD (n = 82) and NPSD groups (n = 115) had a total prevalence rate of 41.6%. The prevalence of PSD in men was 58.5%, whereas that in women was 41.5%, and no statistically significant difference existed between the two groups (χ2 = 1.009; p = 0.315). The CC, CT, and TT frequencies of the PSD group were 26.8%, 47.6%, and 25.6%, respectively, whereas those of the NPSD group were 42.6%, 45.2%, and 12.2%, respectively. Based on the CC genotype, the relative risk of homozygous mutant TT was 3.341 (χ2 = 7.869; p = 0.005; OR = 3.341), and the T allele frequency in the PSD group was 49.4% higher than that in the NPSD group. The locus gene frequency was 34.8%, and the relative risk of allele T relative to allele C was 1.830 (χ2 = 8.381; p = 0.004; OR = 1.830). A certain correlation exists between the C3435T gene polymorphism and PSD in the Han population in South Anhui Province, China, and further studies are needed to confirm our findings.


Cross talk between keratinocytes and dendritic cells: impact on the prediction of sensitization.
Understanding the mechanistic aspects involved in sensitization by chemicals will help to develop relevant preventive strategies. Many potential sensitizers are not directly immunogenic but require activation outside or inside the skin by nonenzymatic oxidation (prehaptens) or metabolic transformation (prohaptens) prior to being able to induce an immune response. This necessary activation step has not yet been actively integrated into a cell line-based prediction approach. We cocultured HaCaT keratinocytes with THP-1 as dendritic cell-like cells allowing intercellular interactions. The sensitizing potential was determined by analyzing differences in the expression of CD86, CD40, and CD54 on cocultured THP-1 cells. This new assay setup allowed (1) to distinguish irritants from allergens without influencing cell viability and (2) to discriminate pre/prohaptens from haptens. Under coculture conditions, the prohaptens eugenol, 2-methoxy-4-methylphenol, and benzo[a]pyrene induced a significantly higher upregulation of CD86 expression on THP-1. In agreement with the hapten concept, responses to 2,4-dinitrochlorobenzene, Bandrowski's base, and the prehapten isoeugenol were not significantly modified. Inhibition of cytochrome P450 or NAD(P)H:quinone oxidoreductase (NQO1) activity reduced the prohapten-mediated upregulation of CD86 on cocultured THP-1 cells. This coculture assay allowing cross talk between HaCaT and THP-1 cells appears to be suitable for the detection of prohaptens, is reproducible, easy to perform, and avoids donor variations. In addition, this assay is a promising approach to understand the impact of cross talk on the prediction of sensitization and once established may be integrated in a future in vitro toolbox to detect potential skin sensitizers and may thus contribute to reduce animal testing.


Biomechanics and visual-motor control: how it has, is, and will be used to reveal the secrets of hitting a cricket ball.
Cricket batting is an incredibly complex task which requires the coordination of full-body movements to successfully hit a fast moving ball. Biomechanical studies on batting have helped to shed light on how this intricate skill may be performed, yet the many different techniques exhibited by batters make the systematic examination of batting difficult. This review seeks to critically evaluate the existing literature examining cricket batting, but doing so by exploring the strong but often neglected relationship between biomechanics and visual-motor control. In three separate sections, the paper seeks to address (i) the different theories of motor control which may help to explain how skilled batters can hit a ball, (ii) strategies used by batters to overcome the (at times excessive) temporal constraints, and (iii) an interpretation from a visual-motor perspective of the prevailing biomechanical data on batting.


Selective reduction of a PDZ protein, SAP-97, in the prefrontal cortex of patients with chronic schizophrenia.
Many postsynaptic density proteins carrying postsynaptic density-95/discs large/zone occludens-1 (PDZ) domain(s) interact with glutamate receptors to control receptor dynamics and synaptic plasticity. Here we examined the expression of PDZ proteins, synapse-associated protein (SAP) 97, postsynaptic density (PSD)-95, chapsyn-110, GRIP1 and SAP102, in post-mortem brains of schizophrenic patients and control subjects, and evaluated their contribution to schizophrenic pathology. Among these PDZ proteins, SAP97 exhibited the most marked change: SAP97 protein levels were decreased to less than half that of the control levels specifically in the prefrontal cortex of schizophrenic patients. In parallel, its binding partner, GluR1, similarly decreased in the same brain region. The correlation between SAP97 and GluR1 levels in control subjects was, however, altered in schizophrenic patients. SAP102 levels were also significantly reduced in the hippocampus of schizophrenic patients, but this reduction was correlated with sample storage time and post-mortem interval. There were no changes in the levels of the other PDZ proteins in any of the regions examined. In addition, neuroleptic treatment failed to mimic the SAP97 change. These findings suggest that a phenotypic loss of SAP97 is associated with the postsynaptic impairment in prefrontal excitatory circuits of schizophrenic patients.


Empirical lessons about occupational categorization from case studies of unemployment.
Scrutiny regarding the typological categorization of occupation (e.g., occupation as work, rest, or leisure) has prompted interest in experiential categories as a less exclusionary alternative. Empirical research can extend the dialogue about categorization by demonstrating how people in particular situations apply and generate occupational categories. This article explores how adults without work utilized typological and experiential categorizations when discussing their occupations. Data were generated via a secondary analysis of interview transcripts from three ethnographic case studies. Study consultants gravitated toward experiential rather than typological categorizations, emphasizing the social, chosen, purposeful, and temporal qualities of their occupational engagement. Occupational therapy practitioners and researchers must explicitly state how and why they categorize occupations with clients and research participants. Whereas typological categories can be used to initiate discussions about occupation, open questions paired with consultant-generated experiential categories may better capture occupational engagement and reveal potential injustices in situations like unemployment


Temporal relationship between the onset of oestrus, the preovulatory LH surge and ovulation in farmed fallow deer, Dama dama.
A study was conducted to determine the timing of ovulation relative to the onset of oestrus and the preovulatory LH surge in fallow deer. Mature fallow does were randomly allocated to two treatments (N = 10 per treatment) designed to synchronize oestrus on or about 17 May. Does assigned to Group 1 (prostaglandin-induced oestrus) each initially received single intravaginal CIDR [Controlled Internal Drug Release] devices for 13 days followed by an i.m. injection of 750 mg cloprostenol on Day 12 (15 May) of the subsequent luteal cycle. Does assigned to Group 2 (progesterone-induced oestrus) each received CIDR devices for 13 days, with withdrawal occurring on 15 May. All does were run with crayon-harnessed bucks (10:1 ratio) from the start of synchronization (18:00 h 15 May). Ten does (5 per group) were blood sampled via indwelling jugular cannulae every 2 h for 72 h from cloprostenol injection or CIDR device withdrawal and the plasma was analysed for concentrations of progesterone and LH by radioimmunoassay. Does within each treatment were randomly allocated to an ovarian examination time of 12, 16, 20 or 24 h after the onset of oestrus. Laparoscopy was repeated at 12-h intervals until ovulation was recorded. The ovaries of does failing to exhibit oestrus were examined 72 and 86 h after cloprostenol injection or CIDR device withdrawal. A total of 17 does were observed to exhibit oestrus at a mean (+/- s.e.m.) interval from treatment of 44.6 +/- 3.6 h for Group 1 (N = 9) and 34.1 +/- 2.5 h for Group 2 (N = 8).(ABSTRACT TRUNCATED AT 250 WORDS)


Fenretinide does not block visual pigment formation in the rat.
Abnormal retinal function has been reported in patients receiving the synthetic retinoid fenretinide. In this study, the vitamin A deprived rat was used as a model to test the possibility that fenretinide is interfering with the vitamin A transport system and/or blocking the normal uptake of 11-cis retinal into the visual pigment. Assessing retinal function by electroretinogram measurements and visual pigment formation by competition studies, our data demonstrate normal uptake of vitamin A and normal visual pigment formation in the rat after treatment with the drug.


Radionuclide Imaging of the Molecular Mechanisms Linking Heart and Brain in Ischemic Syndromes.
For the heart and the brain, clinical observations suggest that an acute ischemic event experienced by one organ is associated with an increased risk for future acute events and chronic dysfunction of the reciprocal organ. Beyond atherosclerosis as a common systemic disease, various molecular mechanisms are thought to be involved in this interaction. Molecular-targeted nuclear imaging may identify the contribution of factors, such as the neurohumoral, circulatory, or especially the immune system, by combining specific radiotracers with whole-body acquisition and global as well as regional multiorgan analysis. This may be integrated with complementary functional imaging markers and systemic biomarkers for comprehensive network interrogation. Such systems-based strategies go beyond the traditional organ-centered approach and provide novel mechanistic insights, information about temporal dynamics, and a foundation for future interventions aiming at optimal preservation of function of both organs.


Nickel-catalyzed decarboxylative cross-coupling of perfluorobenzoates with aryl halides and sulfonates.
A Ni-catalyzed method for the coupling of perfluorobenzoates with aryl halides and pseudohalides is described. Aryl iodides, bromides, chlorides, triflates, and tosylates participate in these transformations to afford the products in good yields. Penta-, tetra-, and trifluorinated biaryl compounds are obtained using these newly developed Ni-catalyzed decarboxylative cross-coupling reactions.


Modern splinting bandages.
We have assessed the current range of synthetic splinting bandages, using physical and mechanical tests and the subjective opinions of patients, volunteers and orthopaedic staff. Modern bandages have some better properties than standard plaster bandage but do not conform as well, are more expensive, and potentially more hazardous.


Mechanisms of ultraviolet-induced melasma formation: A review.
Melasma, a pigmentation disorder, commonly occurs in exposed skin areas and can be attributed to several factors. Ultraviolet radiation (UVR) is the primary factor that induces and aggravates melasma. Considering gene expression, exposed skin areas experience abnormal gene expression, involving melanin metabolism, oxidative stress, impaired skin barrier function, and abnormal composition of nerve factors. From a histological perspective, UVR can cause basement membrane collapse, melanocyte sinking, and disorders of skin lipid metabolism. Emerging therapies have focused on these pathological alterations in melasma, including platelet-rich plasma, mesotherapy, and phytochemicals. Understanding the role of UVR in the development of melasma can facilitate early prevention and highlight the future direction of melasma treatment.


[Modern trends in anti-VEGF therapy for age-related macular degeneration].
Age-related macular degeneration (AMD) develops in people aged 50 years and older, its pathogenesis involves progressive destruction of the retinal pigment epithelium and Bruch's membrane. There are eight currently known anti-VEGF drugs for treating the neovascular form of AMD, four of them have already been registered and are used in clinical practice. The first registered drug was pegaptanib, which selectively blocks VEGF165. Subsequently, a molecule with a similar mechanism of action was developed and named ranibizumab, which is a humanized monoclonal Fab fragment; it was specifically designed for ophthalmology. Its advantage over pegaptanib was neutralization of all active VEGF-A isoforms. Aflibercept and conbercept are recombinant fusion proteins that act as soluble decoy receptors for VEGF family proteins. Phase III data from the VIEW 1 and 2 studies showed that intraocular injections (IVI) of aflibercept every 1 or 2 months for a year resulted in comparable functional outcomes to monthly IVI of ranibizumab for one year. The next molecule for anti-VEGF therapy that showed effectiveness was brolucizumab - a single-chain fragment of a humanized antibody that binds with high affinity to various VEGF-A isoforms. Simultaneously with studying brolucizumab, another study was conducted involving Abicipar pegol, but that drug showed a high rate of complications. The latest drug registered for the treatment of neovascular AMD is faricimab. The molecule of this drug is a humanized immunoglobulin G antibody that acts on two key points of angiogenesis: VEGF-A and angiopoietin-2 (Ang-2). Thus, the strategy for advancing anti-VEGF therapy lies in the development of molecules with greater efficiency (better effect on newly formed vessels leading to resorption of exudate in the retina, under the neuroepithelium and under the retinal pigment epithelium), which allows not just to preserve vision, but to also significantly improve it when there is no macular atrophy.


Brain natriuretic peptide-like immunoreactive innervation of the cardiovascular and cerebrovascular systems in the rat.
Atrial natriuretic peptide is a potent dilator of aorta and renal and cerebral arteries and inhibits sympathetic tone in the heart in several mammalian species. We examined the possibility that a molecule related to porcine brain natriuretic peptide (pBNP), which acts at the same receptor sites as atrial natriuretic peptide, might provide an alternative source of natriuretic peptide to the cardiovascular system in the rat. An antiserum against pBNP demonstrated profuse immunoreactive innervation of the heart, cerebrovascular tree, and renal arteries. pBNP-like immunoreactive fibers ran in bundles along the surface of the heart, innervating the atria most heavily and penetrating the ventricular myocardium along the coronary arteries. There was greater density of innervation of the right side of the heart compared with the left, particularly in the ventricles, suggesting a parasympathetic origin. The entire cerebrovascular tree was innervated by immunoreactive pBNP fibers, with the densest concentration of immunoreactive fibers along the surface of the internal carotid, middle cerebral, posterior communicating, and anterior cerebral arteries. The proximal renal arteries were not innervated, but as they approached the kidney, they were invested by bundles of immunoreactive pBNP fibers. These axons followed the major branches of the renal artery into the kidney parenchyma, running along the surface of the arterioles up to their entrance into the renal glomeruli. No immunoreactive innervation of the aorta or proximal brachiocephalic, subclavian, or carotid arteries was seen. A substance related to pBNP may serve as a neuromodulator regulating cardiac output as well as blood flow in certain vascular beds.


Systemic administration of probiotics reduces the severity of apical periodontitis.
To evaluate the effect of systemic administration of probiotics on the severity of apical periodontitis (AP). Twenty-four male Wistar rats were used. AP was induced in the maxillary left/right first molars. The animals were arranged into groups: Control, Lactobacillus rhamnosus, and Lactobacillus acidophilus. Probiotics were administered orally for gavage (109 colony-forming units diluted in 5 mL of water for 30 days) during the development of AP. After 30 days, cardiac puncture was performed to analyse the complete blood count. Moreover, microbiological analysis of the root canal contents and saliva was performed. Then, the animals were euthanized and the jaw removed for histopathological and IL-10, IL-1β and IL-6 immunolabeling analyses. After the Shapiro-Wilk test of normality, the Kruskal-Wallis followed by Dunn's test was performed for nonparametric data, and analysis of variance followed by the Tukey test was performed for parametric data (P < 0.05). No significance difference was observed in the blood profiles and in the counts of microorganisms from the saliva samples among the groups (P > 0.05). Total microorganism counts in the root canal, the inflammatory infiltrate and the immunostaining for IL-1β and IL-6 in AP were significantly lower in the probiotic groups when compared with the control group (P < 0.05). IL-10 was significantly more immunolabled in the probiotic groups than in the control group (P < 0.05). Supplementation with probiotics (Lactobacillus rhamnosus and Lactobacillus acidophilus) had a significant effect on the severity of apical periodontitis in rats, demonstrating the anti-inflammatory effect of probiotics on the development of apical periodontitis.


cGMP-dependent protein kinase protects cGMP from hydrolysis by phosphodiesterase-5.
The physiological effects of cGMP are largely determined by the activities of intracellular receptors, including cGMP-dependent protein kinase (PKG) and cGMP-binding cyclic nucleotide phosphodiesterases (PDEs), and the distribution of cGMP among these receptors dictates activity of the signalling pathway. In the present study, the effects of PKG-Ialpha or PKG-Ibeta on the rate of cGMP hydrolysis by the isolated PDE5 catalytic domain were examined. PKG-Ialpha strongly inhibited cGMP hydrolysis with an IC(50) value of 217 nM, which is similar to the physiological concentration of PKG in pig coronary artery reported previously. By contrast, PKG-Ibeta, which has lower affinity for cGMP than does PKG-Ialpha, inhibited cGMP hydrolysis with an IC(50) of approx. 1 microM. Inhibition by PKG-Ialpha was more effective than that by PKG-Ibeta, consistent with their relative affinities for cGMP. Autophosphorylation of PKGs increased their cGMP-binding affinities and their inhibitory effects on PDE5 hydrolysis of cGMP. Autophosphorylation of PKG-Ibeta increased its inhibitory potency on PDE5 hydrolysis of cGMP by 10-fold compared with a 2-fold increase upon autophosphorylation of PKG-Ialpha. The results indicate that cGMP bound to allosteric cGMP-binding sites of PKG is protected from hydrolysis by PDE5 and that persistent protection of cGMP by either non-phosphorylated or autophosphorylated PKGs may be a positive-feedback control to sustain cGMP signalling.


Abnormal microvascular reactivity with hypercholesterolaemia in pregnancy.
Post-occlusive skin reactive hyperaemia (PORH) is a model used to assess microvascular reactivity. This study aims to compare PORH response among pregnant hypercholesterolaemic patients with age and gestational age-matched controls. This cross sectional study involved 17 hypercholesterolaemic, pregnant women and 20 pregnant controls entering their early third trimester. Laser Doppler fluximetry (LDF) was used to measure skin perfusion. The process of PORH was performed by occluding the upper arm with an occlusion cuff at 200 mmHg for 3 minutes. Skin perfusion was recorded before, during, and after occlusion release. Baseline perfusion, time to achieve peak perfusion (Tp), peak perfusion after occlusion release (PORH(peak)), and maximum change in perfusion due to occlusion (PORH(max)) were recorded. Serum total cholesterol (TC) was significantly different (P < 0.001) between the 2 groups: 7.25 (SEM 0.18) mmol/L for hypercholesterolaemic women and 5.54 (SEM 0.15) mmol/L for the control group. There were no significant differences in their baseline, PORH(peak), and PORH(max). However, Tp in the hypercholesterolaemic group was significantly increased (P = 0.024) compared with the controls at 14.9 (SEM 0.6) seconds and 13.1 (SEM 0.5) seconds, respectively. Pregnant hypercholesterolaemic patients showed an abnormal microvascular reactivity response. Tp with ischemia was significantly increased compared with normocholesterolaemic controls.


Chocolate and medicine: dangerous liaisons?
According to ancient Mayan texts, cocoa is of divine origin and is considered a gift from the gods. In the Classic period of Mayan civilization (250-900 a.d.), ground cocoa seeds were mixed with seasonings to make a bitter, spicy drink that was believed to be a health-promoting elixir. The Aztecs believed that cocoa pods symbolized life and fertility, and that eating the fruit of the cocoa tree allowed them to acquire wisdom and power. Cocoa was said to have nourishing, fortifying, and aphrodisiac qualities. Pre-Columbian societies were known to use chocolate as medicine, too. The appreciation and popularity of chocolate fluctuated over the centuries since its introduction to Europe from the New World. Now, recent evidence has begun to erase the poor reputation that chocolate had acquired in the past few decades and is restoring its former status. Chocolate is no longer deemed a guilty pleasure, and it may have positive health benefits when eaten in moderation as part of a balanced diet.


Metallization, Material Selection, and Bonding of Interconnections for Novel LTCC and HTCC Power Modules.
Ceramic baseplates are important elements in the power modules of electric drives. This paper presents low-temperature cofired ceramic (LTCC) and high-temperature cofired ceramic (HTCC) materials for the fabrication of three-dimensional power modules. The silver-based metallization and power module assembly are presented, together with aluminum-based power wire bonding and an industrial procedure to achieve high solderability and bondability. The results of the bond tests using different metallization materials, especially cost-effective ones, are presented, together with the assembly of the power modules. The best results were achieved with Ag metallization and 380 µm Al wire and with Ag-Pd metallization and 25 µm Al wire, both on an LTCC base. The paper concludes with a dual-pulse electrical test of the power modules, which proves the quality of metallization, the type of material selected, and the correctness of the wire bonding and assembly.


Interstitial fluid physiology as it relates to glucose monitoring technologies: symposium introduction.
Nearly all commercially available glucose sensors share the subcutaneous interstitial fluid (ISF) compartment as their preferred implantation site. However, ISF physiology as it relates to glucose sensors is not well understood. This special symposium titled "Interstitial Fluid Physiology as It Relates to Glucose Monitoring Technologies" is intended to help to bridge the gap in our understanding. This symposium is intended to foster a greater understanding of biological factors that impact the success of implantable glucose monitors and to inspire additional research in the area of ISF physiology as it relates to glucose sensing. Recognition that sensor designers need to have an intimate understanding of the biological environment in which their sensor will reside is emphasized. The symposium is published in two parts, with part I published in September 2010 and part II published in May 2011. All articles published in this symposium are summarized herein.