Effects of Therapeutic and Aerobic Exercise Programs on Pain, Neuromuscular Activation, and Bite Force in Patients with Temporomandibular Disorders.
Pain in masticatory muscles is one of the most frequent symptoms in patients with temporomandibular disorders (TMD) and can lead to changes in the patterns of neuromuscular activity of masticatory muscles and decrease in bite force. This study assesses the effects of three eight-week exercise programs on pain intensity, neuromuscular activation, and bite force of masticatory muscles in patients with TMD. Forty-five patients were divided into three groups: a therapeutic exercise program (G1), a therapeutic and aerobic exercise program (G2), and an aerobic exercise program (G3). The masticatory muscles' pain was evaluated using the numeric pain rating scale (NPRS), surface electromyographic (sEMG) activity of the masseter was recorded during maximum voluntary contraction and at rest, and bite force was evaluated using a dynamometer. These parameters were evaluated twice at baseline (A01/A02), at the end of the eight-week intervention period (A1), and 8-12 weeks after the end of the intervention (A2). After intervention, G2 showed the best results, with a significantly decrease in masticatory muscles' pain and increase in bite force. These results suggest that interventions to reduce pain in patients with TMD should be multimodal.


The immunogenic and pathogenic potential of short poly(C) tract Mengo viruses.
We have shown previously that genetically engineered Mengo viruses with artificial deletions in their 5' noncoding polyribocytidylic acid (poly(C)) tracts are highly attenuated for the natural murine host and also for other animals such as baboons, macaques, and domestic pigs. The present report further characterizes select short poly(C) tract Mengo viruses in the natural murine host. A positive correlation was found between the length of the poly(C) tract and murine virulence, as measured by virus brain titers and brain lesion scores after infection. Histological examination of brain tissue collected from infected animals clearly showed that the short poly(C) tract viruses did not induce the devastating pathological effects characteristic of animals inoculated with wild-type virus. Instead, the short-tract Mengo viruses proved excellent immunological agents. A dose of only 100 plaque-forming units of vMC24 (poly(C) tract: C13UC10), injected subcutaneously, protected 80% of recipient animals against a normally lethal dose of encephalomyocarditis virus. The protection was long-lived, and animals similarly immunized with vMCo virus (poly(C) tract: Co) still had protective neutralizing antibody titers up to 16 months after inoculation. In addition, the short-tract viruses proved genetically stable, in that the vMC24 virus did not yield detectable pathogenic revertants even after multiple, forced passages in 4-week-old mice. These studies suggest that Mengo viruses containing deletions in their poly(C) tracts are biologically safe and potent immunogens and imply that they may have uses as cardiovirus vaccines.


Hemozoin and the human monocyte--a brief review of their interactions.
In vitro, human monocytes avidly ingest hemozoin (HZ) that modifies a number of monocyte functions. Inhibitory effects: inhibition of: PMA-elicited respiratory burst, ability to killing and repeat phagocytosis, activity of NADPH-oxidase and PKC, expression of ICAM-1, integrin-CD11c, MHC-class-II (IFN-gamma-mediated), differentiation to functional, antigen-presenting dendritic cells. Stimulatory effects: increase in phagocytosis-related respiratory burst and accumulation of lipoperoxidation products; induction of metalloproteinase-9 and pro-inflammatory cytokines and chemokines. Mechanism of action: HZ generates by nonenzymatic catalysis large amounts of lipoperoxidation products, such as monohydroxy derivatives of arachidonic (HETE) and linoleic (HODE) acid, and 4-hydroxynonenal (HNE). Several HZ effects were reproduced by supplementation with plausible concentrations of HETE or HNE, the first most likely via interaction with PPAR-receptors, the second via adduct or crosslinks formation with critical targets.


[Fetal echocardiography in Iceland 2003-2007; indications and outcomes].
The aim of the study was to evaluate the indications and outcomes of fetal echo (FE) and determine which indication has the highest detection rate for congenital heart disease (CHD). The referral indications and results of FE performed in Iceland during 2003-2007 were reviewed. Information regarding gestational age at diagnosis, nuchal translucency, pregnancy outcome, autopsy results and postnatal diagnosis were obtained from medical records. During the five year period 1187 FE were performed. Structural heart defect was diagnosed in 73 fetuses. The most common referral indication was family history of CHD (631;53.2%) which led to diagnosis of 18 heart defects prenatally (2.9%). The second most common referral indication was increased nuchal translucency (159) and abnormal cardiac findings were present in 16 cases (10.1%). A total of 30 women were referred for FE because of abnormal four chamber view (AFCV) which resulted in the diagnosis of 22 (73.3%) major heart defects, either incompatible with life or requiring immediate intervention after birth. Other indications led mostly to the diagnoses of minor defects. AFCV is the most important predictor for diagnosis of structural heart defects. 2,5% were referred for FE due to AFCV which led to diagnosis of 30% of all heart defects, all of which were major. Key words: fetal echocardiography, indications, congenital heart disease.


Recognizing the musculoskeletal manifestations of vitamin D deficiency.
A disruption in any part of the vitamin D physiological pathway can result in vitamin D deficiency, which may lead to bone pain, muscle weakness, falls, low bone mass, and fractures. Recognizing the signs and symptoms helps physicians make a proper diagnosis and prescribe appropriate treatment. Physicians should suspect osteomalacia in patients who have prolonged vitamin D deficiency, a low serum calcium level, or a low serum phosphorus level. Patients with cystic fibrosis are at increased risk for deficiencies in fat-soluble vitamins, including vitamin D. Secondary hyperparathyroidism can develop in patients with chronic kidney disease as a result of low 25-hydroxyvitamin D levels or impaired conversion to 1,25-dihydroxyvitamin D. Patients may experience abnormal vitamin D metabolism as a result of taking anticonvulsants and other medications.


A Novel Molecular Target in EGFR-mutant Lung Cancer Treated With the Combination of Osimertinib and Pemetrexed.
Synergistic effects of epidermal growth factor receptor tyrosine kinase inhibitors and chemotherapy have been reported. Here, we evaluated the therapeutic potential of combining osimertinib with pemetrexed and investigated the molecular mechanisms. We analyzed the antitumor effects of osimertinib± pemetrexed in PC-9 and H1975 cells. Gene expression on exposure to osimertinib±pemetrexed was assessed in these cultured cells. Cell lines resistant to osimertinib±pemetrexed were established to explore mechanisms of resistance. Osimertinib+pemetrexed treatment delayed the emergence of resistance relative to monotherapy in vitro and in vivo. Expression of the anti-apoptotic gene PLK1 was down-regulated in PC-9 and H1975 exposed to osimertinib+ pemetrexed, whereas it was up-regulated in resistant cells. Furthermore, inhibition of PLK1 induced apoptosis and inhibited proliferation of resistant cells. Blocking PLK1 contributes to mediating the synergistic anti-proliferative effect of osimertinib+pemetrexed. PLK1 over-expression may be a critical mechanism for acquired resistance to osimertinib+pemetrexed.


Nurse-led telephone follow-up after total knee arthroplasty--content and the patients' views.
To generate information on how telephone follow-up consultations, structured by nursing status according to the VIPS-model, functioned after total knee arthroplasty. The objectives were to unfold the content of the telephone follow-ups according to the structure for nursing status and to explore the patients' views of the telephone follow-ups. The length of stay in hospital following total knee arthroplasty has fallen markedly, and patients now have to be responsible for their recovery from a very early stage. After discharge, patients may experience a variety of health problems. A clinical trial was conducted to evaluate the effect of telephone follow-up, and information on how the telephone follow-ups functioned is relevant for implementation into clinical practice. A qualitative design was used. One hundred and four case reports from telephone follow-up consultations and individual interviews with 10 patients formed the data material. Content analysis was used for the analysis. The content of the telephone follow-ups included dialogues relating to all key subjects for nursing status except 'culture/spirituality'. The structured Telephone follow-up was valued by total knee arthroplasties patients as representing a holistic approach and providing adequate information, counselling and support after discharge to home. Three categories were identified with regard to the patients' views: 'A means for reflection and provision of adequate information and counselling', 'Supportive' and 'Not the only resource for support and counselling'. Nursing status according to the VIPS model is a comprehensive structure to identify the need for counselling, information and support after total knee arthroplasty. The structured telephone follow-ups were valued for representing a holistic approach and providing adequate information, counselling and support after discharge to home. Conducting telephone follow-up with a holistic approach demands specialised and broad nursing experience. Postdischarge follow-up is important.


A comprehensive simulation framework for imaging single particles and biomolecules at the European X-ray Free-Electron Laser.
The advent of newer, brighter, and more coherent X-ray sources, such as X-ray Free-Electron Lasers (XFELs), represents a tremendous growth in the potential to apply coherent X-rays to determine the structure of materials from the micron-scale down to the Angstrom-scale. There is a significant need for a multi-physics simulation framework to perform source-to-detector simulations for a single particle imaging experiment, including (i) the multidimensional simulation of the X-ray source; (ii) simulation of the wave-optics propagation of the coherent XFEL beams; (iii) atomistic modelling of photon-material interactions; (iv) simulation of the time-dependent diffraction process, including incoherent scattering; (v) assembling noisy and incomplete diffraction intensities into a three-dimensional data set using the Expansion-Maximisation-Compression (EMC) algorithm and (vi) phase retrieval to obtain structural information. We demonstrate the framework by simulating a single-particle experiment for a nitrogenase iron protein using parameters of the SPB/SFX instrument of the European XFEL. This exercise demonstrably yields interpretable consequences for structure determination that are crucial yet currently unavailable for experiment design.


Reversal of a dense, persistent, holohemispheric neurological deficit after an endarterectomy of the carotid artery: case report.
The role and timing of a carotid endarterectomy in the setting of an acute ischemic stroke-in-evolution remain controversial. Although computed tomographic (CT) scans typically show no abnormalities in the acute stage, it is generally agreed that a dense neurological deficit (hemiplegia) and/or multiple modality neurological disturbance (involving motor, sensory, gaze, and visual field impairment) represent contraindications to surgical intervention. We present a case of an acute right holohemispheric neurological deficit including dense hemiplegia, hemisensory loss, gaze disturbance, hemineglect, and impaired level of consciousness. This persisted for 4 days while serial CT scans showed no evidence of infarction. Angiography revealed pre-occlusive stenosis of the right internal carotid artery with sluggish antegrade flow. The anterior collaterals of the circle of Willis were impaired, and the right middle cerebral artery territory filled via the posterior communicating artery. Despite the dense neurological deficit persisting for 4 days, a carotid endarterectomy was performed. Gradual neurological improvement was noted within hours of the operation, and all neurological deficits resolved within the subsequent 3 days. This case is consistent with prolonged holohemispheric hemodynamic compromise below the threshold of neurological dysfunction, but above the threshold of tissue infarction ("idling neurons"). Features assisting in the recognition of this unusual scenario and the indications and risks of revascularization in this setting are discussed.


Leach out of inorganic and trace elements at the time of etching.
The enamel is the hardest biological structure made up of inorganic ions, organic substances, trace elements and water and it covers the coronal part of dentin. Acid etching causes leaching out of inorganic and trace elements from the enamel surface. In the present study leach out pattern of 11 elements from the enamel surface during etching was studied.


NEO-PI profiles in PTSD as a function of trauma level.
One hundred Vietnam veterans with combat-related PTSD were administered the NEO Personality Inventory (NEO-PI) and the Combat Exposure Scale and were sorted into three groups based on trauma exposure level. Results indicate no significant differences among the personality profiles of the three trauma-exposed groups. A normative NEO-PI profile for persons diagnosed with combat-related PTSD is presented, characterized by an extremely high Neuroticism score (T > 75) and an extremely low Agreeableness score (T < 25).


Dysregulation of corticostriatal ascorbate release and glutamate uptake in transgenic models of Huntington's disease.
Dysregulation of cortical and striatal neuronal processing plays a critical role in Huntington's disease (HD), a dominantly inherited condition that includes a progressive deterioration of cognitive and motor control. Growing evidence indicates that ascorbate (AA), an antioxidant vitamin, is released into striatal extracellular fluid when glutamate is cleared after its release from cortical afferents. Both AA release and glutamate uptake are impaired in the striatum of transgenic mouse models of HD owing to a downregulation of glutamate transporter 1 (GLT1), the protein primarily found on astrocytes and responsible for removing most extracellular glutamate. Improved understanding of an AA-glutamate interaction could lead to new therapeutic strategies for HD. Increased expression of GLT1 following treatment with ceftriaxone, a beta-lactam antibiotic, increases striatal glutamate uptake and AA release and also improves the HD behavioral phenotype. In fact, treatment with AA alone restores striatal extracellular AA to wild-type levels in HD mice and not only improves behavior but also improves the firing pattern of neurons in HD striatum. Although evidence is growing for an AA-glutamate interaction, several key issues require clarification: the site of action of AA on striatal neurons; the precise role of GLT1 in striatal AA release; and the mechanism by which HD interferes with this role. Further assessment of how the HD mutation alters corticostriatal signaling is an important next step. A critical focus is the role of astrocytes, which express GLT1 and may be the primary source of extracellular AA.


Caenorhabditis elegans expresses three functional profilins in a tissue-specific manner.
Profilins are actin binding proteins, which also interact with polyphosphoinositides and proline-rich ligands. On the basis of the genome sequence, three diverse profilin homologues (PFN) are predicted to exist in Caenorhabditis elegans. We show that all three isoforms PFN-1, PFN-2, and PFN-3 are expressed in vivo and biochemical studies indicate they bind actin and influence actin dynamics in a similar manner. In addition, they bind poly(L-proline) and phosphatidylinositol 4,5-bisphosphate micelles. PFN-1 is essential whereas PFN-2 and PFN-3 are nonessential. Immunostainings revealed different expression patterns for the profilin isoforms. In embryos, PFN-1 localizes in the cytoplasm and to the cell-cell contacts at the early stages, and in the nerve ring during later stages. During late embryogenesis, expression of PFN-3 was specifically detected in body wall muscle cells. In adult worms, PFN-1 is expressed in the neurons, the vulva, and the somatic gonad, PFN-2 in the intestinal wall, the spermatheca, and the pharynx, and PFN-3 localizes in a striking dot-like fashion in body wall muscle. Thus the model organism Caenorhabditis elegans expresses three profilin isoforms and is the first invertebrate animal with tissue-specific profilin expression.


[Psychiatric rating scales in clinical work].
Psychiatric rating scales can be used to support disease screening and assessment of the severity of symptoms and effectiveness of treatment. In Finland, several rating scales suitable for both the general practitioner and the psychiatrist, are in use. The scales can be applied to mood disorders, anxiety disorders, eating disorders, substance use disorders and to the assessment of symptoms associated with psychoses. It is important not to make a psychiatric diagnosis merely on the basis of the score obtained. The use of appropriate rating scales makes the clinical work easier and quicker.


New rapid detection by using a constant temperature method for avian leukosis viruses.
The avian leukemia virus causes avian leukemia (AL), a severe immunosuppressive disease in chickens (ALV). Since the 1990s, the diversity of ALV subpopulations caused by ALV genome variation and recombination, and the complexity of the infection and transmission, with currently no effective commercial vaccine and therapeutic for ALV, has resulted in severe economic losses to the chicken business in various parts of the world. Therefore, as a key means of prevention and control, an effective, rapid, and accurate detection method is imperative. A new real-time reverse transcription recombinase-aided amplification (RT-RAA) assay for ALV with rapid, highly specific, low-cost, and simple operational characteristics have been developed in this study. Based on the amplification of 114 base pairs from the ALV P12 gene, real-time RT-RAA primers and a probe were designed for this study. The lowest detection line was 10 copies of ALV RNA molecules per response, which could be carried out at 39°C in as fastest as 5 min and completed in 30 min, with no cross-reactivity with Marek's disease virus, avian reticuloendothelial virus, Newcastle disease virus, infectious bronchitis virus, infectious bursal disease virus, infectious laryngotracheitis virus, and avian influenza virus. Furthermore, the kappa value of 0.91 (>0.81) was compared with reverse transcription-polymerase chain reaction (RT-PCR) for 44 clinical samples, and the coefficients of variation were within 5.18% of the repeated assays with three low-level concentration gradients. These results indicate that using a real-time RT-RAA assay to detect ALV could be a valuable method.


Human mitochondrial RNA polymerase primes lagging-strand DNA synthesis in vitro.
The mitochondrial transcription machinery synthesizes the RNA primers required for initiation of leading-strand DNA synthesis in mammalian mitochondria. RNA primers are also required for initiation of lagging-strand DNA synthesis, but the responsible enzyme has so far remained elusive. Here, we present a series of observations that suggests that mitochondrial RNA polymerase (POLRMT) can act as lagging-strand primase in mammalian cells. POLRMT is highly processive on double-stranded DNA, but synthesizes RNA primers with a length of 25 to 75 nt on a single-stranded template. The short RNA primers synthesized by POLRMT are used by the mitochondrial DNA polymerase gamma to initiate DNA synthesis in vitro. Addition of mitochondrial single-stranded DNA binding protein (mtSSB) reduces overall levels of primer synthesis, but stimulates primer-dependent DNA synthesis. Furthermore, when combined, POLRMT, DNA polymerase gamma, the DNA helicase TWINKLE, and mtSSB are capable of simultaneous leading- and lagging-strand DNA synthesis in vitro. Based on our observations, we suggest that POLRMT is the lagging-strand primase in mammalian mitochondria.


Differential impairment patterns of the corticospinal tract segments in alcohol dependence.
Background: Previous studies have reported inconsistent findings regarding corticospinal tract (CST) changes in alcohol dependence. Here, we aimed to clarify this issue by examining the micro-structural integrity differences of distinct CST segments between alcohol-dependent patients and healthy controls. Methods: Diffusion tensor imaging was performed in a total of 39 male individuals, including 19 alcohol-dependent patients and 20 age-matched healthy controls. CST was reconstructed using tractography and was divided into inferior and superior segments at the level of the lateral sulcus. Multiple diffusion measures of each segment were compared between two groups. Results: For the bilateral whole CSTs, no diffusion measures showed significant between-group differences. However, compared to healthy controls, alcohol-dependent patients exhibited decreased FA and increased RD in the left-superior segment, increased FA and decreased RD/MD in the left-inferior segment, increased AD/MD in the right-superior segment, decreased RD/MD in the right-inferior segment. Conclusions: These findings suggest that CST impairments may vary with the fibre arrangement patterns of its segments in alcohol dependence. Keypoints We reconstructed the CST using tractography based on DTI data and divided the CST into different segments in order to explore more detailed micro-structural integrity changes in alcoholisms. Alcohol-dependent patients showed decreased RD and MD for the bilateral inferior segments of the CSTs. The left-superior segment exhibited decreased FA and increased RD while the right one exhibited increased AD and MD. These findings suggest that CST impairments may vary with the fiber arrangement patterns of its segments in alcohol dependence. In future work, more elaborate segmentation schemes and lager samples should be used to test the reproducibility of our findings.


Perinatal iron deficiency combined with a high-fat diet causes obesity and cardiovascular dysregulation.
Consumption of a high-fat Western diet (WD) and the resultant obesity is linked to a number of chronic pathologies, including cardiovascular dysregulation. The purpose of the present study was to determine whether perinatal iron deficiency (PID) added to the consumption of a WD would precipitate an obese phenotype with exacerbated metabolic and cardiovascular outcomes in adult offspring. Female Sprague Dawley rats were fed either a control (225 mg/kg Fe) or an iron-restricted diet (3-10 mg/kg Fe) prior to and throughout gestation. At birth, all dams were fed an iron-replete diet. At weaning, offspring were fed a normal diet or WD for up to 21 wk. Hemodynamics and locomotor activity were assessed by radiotelemetry starting at 15 wk of age. Iron restriction during pregnancy caused severe anemia in dams and offspring, resulting in 15% lower birth weights in the offspring. PID offspring fed the WD had greater caloric intake and exhibited reduced locomotor activity compared with their normal diet-fed littermates; no such effects were observed in normal iron control offspring. Despite having a similar effect on serum lipid profiles, consumption of the WD had a greater impact on body weight in the PID group, and this weight gain was due largely to visceral adipose tissue accumulation. A significant correlation between visceral adipose tissue weight and mean arterial pressure was observed in the PID offspring but not in controls. These observations demonstrate that PID predisposes offspring to an enhanced response to WD characterized by increased fat accumulation and cardiovascular dysregulation.


[Analysis on the current situation and influencing factors of mental health among female employees].
Objective: To understand the mental health status of female workers in different industries in China, and to explore the influence of age, family per capita income, working hours and other factors on the mental health of female employees. Methods: From May to July 2016, a cluster sampling survey was conducted among female workers from 15 Provinces (autonomous regions and municipalities directly under the Central Government) in different industries. A total of 60230 questionnaires were distributed and 57777 valid questionnaires were recovered, with an effective rate of 95.9%. The survey included the basic information and Symptom Self-assessment Scale, etc. The measured data were in accordance with the normal distribution by normality test and were expressed as x±s. The rates of counting data were compared using the χ(2) test. And unconditioned logistic regression was used to analyze the influencing factors. Results: There were significant differences in the detection rates of mental health problems among female employees of different ages, marital status, education level, family per capita income, industry classification, working hours, and frequent night shifts (P<0.01) . The top 3 factors of positive mental health problems were obsessive-compulsive symptoms (23.7%) , depression (16.0%) and interpersonal sensitivity (15.4%) . The factors such as age, education level, family per capita income, industry classification, working hours and frequent night shifts had statistical significances on the risk of female employees' mental health problems (P<0.05) . Female employees aged 30-39, aged 40-49, with high school education to junior college, bachelor degree or above, engaged in tertiary industry, working time of 8-9 h/d, working time of 9-11 h/d, working time of more than 11 h/d and regular night shifts had higher risk of mental health problems (OR=1.199, 1.187, 1.296, 1.539, 1.236, 1.674, 1.601, 1.358, 1.393, P<0.05) . Conclusion: The mental health problems of female workers are still serious, we should pay attention to the illegal long-term work and night-shift work, and take effective health promotion measures to effectively improve the mental health level of female workers.


Neuropeptide Y damages the integrity of mitochondrial structure and disrupts energy metabolism in cultured neonatal rat cardiomyocytes.
Neuropeptide Y (NPY) plays an important role in cardiovascular diseases including stress cardiomyopathy, hypertrophic cardiomyopathy, heart failure, diabetic cardiomyopathy, hypertension, and so on. However, inconsistent results related to the role of NPY in the different types of cardiomyopathies make the exact involvement of the peptide elusive. Considering these effects are known to be involved in energy balance, as the hearts energy producer, the mitochondria, should be investigated, and not only mitochondrial structure but also its potential. Up to now, the impact of NPY on energy metabolism and mitochondria in cultured neonatal rat cardiomyocytes has not been reported. The main objective of our study was to test the role of NPY in cultured neonatal rat cardiomyocytes. After 24-h stimulation of NPY, the ATP content and activity of the cardiomyocytes were determined by Cell Counting Kit-8 and ATP-dependent bioluminescence assay kit, respectively. To further measure these effects, mitochondrial membrane potential was measured by JC-1 staining, the change of mitochondrial structure was detected by transmission electron microscopy, and the levels of PGC-1α (a marker of mitochondrial energy metabolism) mRNA and protein expression were determined by real-time PCR and Western blotting, respectively. The results showed that after 24-h stimulation of NPY, ATP content and activity in the cardiomyocytes were decreased. Moreover, cardiomyocyte mitochondria were changed in morphology. Further, a decline of mitochondrial membrane potential was induced in a dose-dependent manner and the levels of PGC-1α mRNA and protein expression were up-regulated after being treated by different dose of NPY. The results indicate that energy metabolism is suppressed, mitochondrial structure and membrane potential damaged, and PGC-α is changed in cultured neonatal rat cardiomyocytes after being treated by NPY.


Violence against girls during COVID-19 pandemic and associated factors in Gondar city, North West Ethiopia.
In Ethiopia, the magnitude of violence against girls during COVID-19 in the study area is not known. Therefore, this study aimed to assess the violence and associated factors during COVID-19 pandemic among Gondar city secondary school girls in North West Ethiopia. An institution-based cross-sectional study was conducted from January to February 2021. Data were collected from four public and two private Gondar city secondary schools. Investigators used stratified simple random sampling to select participants and the investigators used roster of the students at selected schools. Investigators collected the data using self-reported history of experiencing violence (victimisation). Investigators analysed data using descriptive statistics and multivariable logistic regression. Investigators invited a total of 371 sampled female students to complete self-administered questionnaires. The proportion of girls who experienced violence was 42.05% and psychological violence was the highest form of violence. Having a father who attended informal education (AOR = 1.95, 95% CI 1.08-3.51), ever use of social media 1.65 (AOR = 1.65, 95% CI 1.02-2.69), ever watching sexually explicit material (AOR = 2.04, 95% CI 1.24-3.36) and use of a substance (AOR = 1.92, 95% CI 1.17-3.15) were significantly associated variables with violence. Almost for every five girls, more than two of them experienced violence during the COVID-19 lockdown. The prevalence of violence might be under reported due to desirability bias. Therefore, it is better to create awareness towards violence among substance users, fathers with informal education and social media including user females.


Ischemic stroke injury is reduced in mice lacking a functional NADPH oxidase.
Free radicals account for a significant proportion of the brain damage that occurs during ischemic stroke. Using mutant mice (X-CGD) with a dysfunctional phagocytic NADPH oxidase, we investigated the role of this superoxide-generating enzyme as a mediator of the reperfusion injury in a mouse model of middle cerebral artery occlusion. Transient (2 hour) middle cerebral artery occlusion was performed in X-CGD or wild-type litter mates (8- to 10-week-old). After 22 hours of reperfusion, brains were harvested and infarct volume delineated using 2,3,5-triphenyl-tetrazolium chloride. To elucidate the origin of the damaging NADPH oxidase, transient ischemia was also performed in X-CGD or wild-type mice transplanted with wild-type C57 B1/6J or X-CGD bone marrow, respectively. The infarct volume induced by transient ischemia was significantly less in X-CGD mice (29.1 +/- 5.6 mm3; n = 13) than wild-type littermates (54.0 +/- 10.6 mm3; n = 10; P < .05). The elimination of a functional NADPH oxidase from either the circulation or the central nervous system, by performing the appropriate bone marrow transplant experiments, did not reduce the infarct size induced by transient ischemia. This suggests that in order to confer protection against transient ischemia and reperfusion, a putative neuronal and circulating NADPH oxidase need to be inactivated. Brain injury was reduced in mice lacking a functional NADPH oxidase in both the central nervous system and peripheral leukocytes, suggesting a pivotal role for the NADPH oxidase in the pathogenesis of ischemia-reperfusion injury in the brain.


Leukocyte adhesion and thrombosis.
The consequences of arterial thrombosis such as myocardial infarction, stroke and peripheral vascular occlusion are the leading causes of morbidity and mortality. A high leukocyte count and an elevation in inflammatory markers are identified as significant risk factors for thrombosis. Leukocytes form the front line in defense against infection and are the first cells arriving at the site of inflammation. This review summarizes the cellular and molecular mechanisms by which adherent leukocytes can induce a prothrombotic state. Circulating tissue factor has been recognized as a potential prothrombotic factor initiating thrombosis after vascular injury. The tissue factor is present on microvesicles originated from activated leukocytes. Leukocytes generate tissue factor containing microvesicles following stimulation with cytokines and following platelet adhesion via P-selectin. Additionally, activated leukocytes release several mediators, such as cathepsin G and elastase, which can activate both the coagulation cascade and platelets. Furthermore, new roles for leukocytes have been identified in vascular injury in sickle cell anemia, in vascular occlusion following the rupture of atherosclerotic plaque, and in thrombotic complications of myeloproliferative diseases. Leukocyte adhesion to endothelium and platelets plays an important role in the activation of the coagulation cascade. An excessive activation of leukocytes during the inflammatory process may induce a systemic procoagulant state. Elucidation of critical steps in activation of coagulation by leukocytes may offer a new therapeutic target for antithrombotic therapy based on blocking leukocyte adhesion.


Species-specific cell wall binding affinity of the S-layer proteins of mosquitocidal bacterium Bacillus sphaericus C3-41.
The binding affinities and specificities of six truncated S-layer homology domain (SLH) polypeptides of mosquitocidal Bacillus sphaericus strain C3-41 with the purified cell wall sacculi have been assayed. The results indicated that the SLH polypeptide comprised of amino acids 31 to 210 was responsible for anchoring the S-layer subunits to the rigid cell wall layer via a distinct type of secondary cell wall polymer and that a motif of the recombinant SLH polypeptide comprising amino acids 152 to 210 (rSLH(152-210)) was essential for the stable binding of the S-layer with the bacterial cell walls. The quantitative assays revealed that the K(D) (equilibrium dissociation constant) values of rSLH(152-210) and rSLH(31-210) with purified cell wall sacculi were 1.11 x 10(-6) M and 1.40 x 10(-6) M, respectively. The qualitative assays demonstrated that the SLH domain of strain C3-41 could bind only to the cell walls or the cells treated with 5 M guanidinium hydrochloride of both toxic and nontoxic B. sphaericus strains but not to those from other bacteria, indicating the species-specific binding of the SLH polypeptide of B. sphaericus with bacterial cell walls.


Telomere dysfunction in some pediatric congenital and growth-related diseases.
Telomere wear and dysfunction may lead to aging-related diseases. Moreover, increasing evidence show that the occurrence, development, and prognosis of some pediatric diseases are also related to telomere dysfunction. In this review, we systematically analyzed the relationship between telomere biology and some pediatric congenital and growth-related diseases and proposed new theoretical basis and therapeutic targets for the treatment of these diseases.


Frequency of the use of biological treatment of patients with rheumatoid arthritis and ankylosing spondylitis in Lower Silesia.
Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are chronic connective tissue diseases. Inadequate treatment of RA and AS results in health failure, disability and premature death. In recent years, development of immunology and genetic engineering techniques has started a new generation of drugs in the treatment of RA and AS, called biologic response modifiers or biologics. It is a very effective therapy of serious RA and AS. In many cases, they represent the only way to improve the quality of life, slowing or even arresting the development of these diseases. According to national statistics, the percentage of patients with rheumatic diseases treated with biologic treatment in Poland is less than 1.5%, and it is much lower than in Western European countries (20%). The aim of the study was to evaluate the use of biological treatment in Lower Silesia in patients with RA and AS in the years 2006-2015, based on data obtained from the Lower Silesian Branch of the Polish National Health Fund. In the last 10 years the frequency of biological treatment of RA or AS in Lower Silesia was estimated as 2.06% of patients (in 2011) to 6.03% of patients (during the first 8 months of 2015). Biological treatment is more often used in Lower Silesia in comparison to national statistics and ranks at a similar level as in other countries of Central and Eastern Europe.


Signal termination in bacterial chemotaxis: CheZ mediates dephosphorylation of free rather than switch-bound CheY.
Chemotaxis in bacteria is controlled by regulating the direction of flagellar rotation. The regulation is carried out by the chemotaxis protein CheY. When phosphorylated, CheY binds to FliM, which is one of the proteins that constitute the "gear box" (or "switch") of the flagellar motor. Consequently, the motor shifts from the default direction of rotation, counterclockwise, to clockwise rotation. This biased rotation is terminated when CheY is dephosphorylated either spontaneously or, faster, by a specific phosphatase, CheZ. Logically, one might expect CheZ to act directly on FliM-bound CheY. However, here we provide direct biochemical evidence that, in contrast to this expectation, phosphorylated CheY (CheY approximately P), bound to FliM, is protected from dephosphorylation by CheZ. The complex between CheY approximately P and FliM was trapped by cross-linking with dimethylsuberimidate, and its susceptibility to CheZ was measured. CheY approximately P complexed with FliM, unlike free CheY approximately P, was not dephosphorylated by CheZ. However, it did undergo spontaneous dephosphorylation. Nonspecific cross-linked CheY dimers, measured as a control, were dephosphorylated by CheZ. No significant binding between CheZ and any of the switch proteins was detected. It is concluded that, in the termination mechanism of signal transduction in bacterial chemotaxis, CheZ acts only on free CheY approximately P. We suggest that CheZ affects switch-bound CheY approximately P by shifting the equilibrium between bound and free CheY approximately P.


Impetigo.
Impetigo is a common superficial bacterial infection of the skin, with a global disease burden of greater than 140 million. Children are more affected than adults and incidence decreases with age. Principal pathogens implicated include Staphylococcus aureus and Streptococcus pyogenes. There are two common variants of impetigo: nonbullous (70%) and bullous (30%). Nonbullous impetigo is caused by S. aureus and S. pyogenes whereas bullous impetigo is caused by S. aureus. The classic appearance of distinctive honey-colored, crusted legions aids in diagnosis, which is most often based on clinical presentation. The disease is generally mild and felt to be self-limited; however, antimicrobial treatment is often initiated to reduce spread and shorten clinical course. Treatment for limited impetigo is topical whereas oral therapy is recommended for extensive cases. Rising rates of bacterial resistance to standard treatment regimens should inform treatment decisions. Complications, while rare, can occur.


Endonuclear lipids in liver cells.
Lipids are not only components of cell nucleus membranes, but are also found in the membrane-depleted nuclei where they fulfill special functions. We have investigated the lipid composition of membrane-depleted rat liver nuclei obtained by incubation with low Triton X-100 concentrations of 0.04% and 0.08%, which rendered them unaltered or hardly altered. Under these conditions, 26% of proteins and 22% of phospholipids were recovered. The main phospholipids were phosphatidylcholine > phosphatidylethanolamine > phosphatidylinositol = or > phosphatidylserine and sphingomyelin (in decreasing concentrations). The fatty acid components of total lipids and phosphatidylcholine were mainly unsaturated. Over 40% belonged to the n-6 series (arachidonic > or = 25% and linoleic 15%); approximately 40% corresponded to saturated acids and <10% were monoenoic. Endonuclear phosphatidylcholine was built up by 16 molecular species, the most abundant being 18:0-20:4 (32%), 16:0-20:4 (19%), 16:0-18:2 (13%), and 18:0-18:2 (11%). The fatty acid composition and phosphatidylcholine molecular species distribution in the membrane-depleted nucleus of rat liver showed patterns similar to the whole nucleus, mitochondria, microsomes, and homogenate of the parent liver cells, suggesting that endonuclear lipid pool composition is mainly determined by a liver organ profile.


Characterization of a 60-kDa Thermally Stable Antigenic Protein as a Marker for the Immunodetection of Bovine Plasma-Derived Food Ingredients.
A sandwich enzyme-linked immunosorbent assay (sELISA) based on 2 monoclonal antibodies (Bb3D6 and Bb6G12) that recognize a 60-kDa antigenic protein in bovine blood was previously developed for detecting bovine blood in animal feed for the prevention of mad cow disease. This study sought to establish the identity of this 60-kDa antigenic protein and consequently determine the suitability of the sELISA for detecting bovine plasma-derived food ingredients (BPFIs), which are widely used in dietary products without explicit labeling. Results from western blot confirmed the 60-kDa protein to be present in the plasma fraction of bovine blood. Further proteomic analyses involving 2-dimensional gel electrophoresis (2-D GE) and amino acid sequencing revealed the 60-kDa protein to be bovine serum albumin (BSA). The sELISA proved capable of detecting BPFIs in all the commercial dietary supplements tested, including those that were formulated with hydrolyzed BPFIs. The assay could also detect 0.01% and 0.5% of different BPFIs in spiked raw and cooked ground beef, respectively. This assay based on the detection of BSA therefore has the potential to become a valuable analytical tool to protect consumers who avoid consuming BPFIs for religious, health, or ethical reasons.


Variability of breathlessness measurement in patients with chronic obstructive pulmonary disease.
The purpose of our study was to evaluate the reproducibility of a Borg rating of dyspnea in patients with COPD. We examined nine patients with COPD who performed a SST on four separate days within a ten-day period. The patients walked on a treadmill for 6 min. At the end of each minute, patients matched a Borg rating to the intensity of their breathlessness. We measured the HR, VE, VO2, VT and f at the end of each minute. While the mean VO2, VE, HR, VT and f stabilized after one or two attempts, the Borg ratings decreased with successive tests. We conclude that the Borg scale for measuring breathlessness shows progressive decreases with repetition whereas VO2, VE, HR, VT and f stabilize after one or two practice attempts. This suggests that desensitization to dyspnea may play a role in the improvement of patients after exercise.


S-Adenosyl Methionine in the Therapy of Depression and Other Psychiatric Disorders.
Preclinical Research S-adenosyl methionine (SAM) is a major methyl donor and as such exerts its influence on CNS function through methylation reactions, such as methylation of several catecholamine moiety-containing neurotransmitters, epigenetic changes through methylation of DNA, RNA, RNA-binding proteins and histones, and phospholipid methylation. Based on available evidence, SAM is currently recommended as a next-step (second-line) treatment option following inadequate treatment response to a first-line antidepressant. It shows significant promise in the treatment of pediatric and perinatal depression, as well as Alzheimer's disease, but to make this a recommendation further clinical trials are needed. SAM is safe to use in most patients, but is contraindicated in those with bipolar disorder. Concerns considering the possible increase of homocysteine levels (and cardiovascular complications) due to long-term SAM therapy need to be further addressed in clinical trials taking into account individual`s ability to metabolize homocysteine and his/her folate status. Drug Dev Res 77 : 336-346, 2016. © 2016 Wiley Periodicals, Inc.


A modified digitonin-precipitation radioassay for 3 beta-hydroxy-delta 5-steroid dehydrogenase.
An improved digitonin-precipitation radioassay for 3 beta-hydroxy-delta 5-steroid dehydrogenase is presented. It is linear for enzyme protein concentrations up to 0.6 mg and for 37 degrees C incubation times up to 10 min. Sensitivity and reproducibility are improved nine- and sevenfold, respectively, over the method of Philpott and Peron. There is a good correlation with the Philpott and Peron assay (r = 0.958) and with a thin-layer chromatography method (r = 0.997). Beyond being faster, simpler, and more sensitive than other analyses, this radioassay uses one-tenth the quantity of [3H]pregnenolone substrate and is, therefore, a safer and less expensive procedure.


Small-angle diffusing screens for photolithographic camera illumination systems.
A method is described for producing transmitting screens that diffuse light into small angles. With these screens, the amount of small-angle diffusion can be controlled while light loss from large-angle scattering is kept to a minimum. The diffusers are fabricated from two glass substrates that are ground, etched, and cemented together. There is a controlled mismatch between the optical index of the cement and that of the substrates. The screens were primarily designed for photolithographic camera illumination systems that involve a tradeoff between luminance and uniformity.


Monitoring cyclosporine in liver-transplant recipients: effects of clinical status on the performance of two monoclonal antibody-based methods.
The characteristics of the Abbott selective fluorescence polarization immunoassay for cyclosporine in whole blood (TDXSP) were compared with the Incstar radioimmunoassay by using kit standards (INCSP) or TDXSP standards (INCTDX) with samples from adult (48) and pediatric (24) liver-transplant recipients and a further 32 control specimens. The TDXSP assay was faster, less labor intensive, and more precise at higher concentrations; it gave results a median of 5 micrograms/L lower than INCSP values, irrespective of biliary T-tube status, patient's age, or severity of cholestasis in nine patients, comparisons being made for serum bilirubin more than eight times normal or less than 50 mumol/L. However, both assays overestimated INCTDX values by approximately 10%. There was a progressive increase in the ratio of TDXSP to both INCSP and INCTDX results in 57 samples stratified in relation to serum bilirubin concentrations. Cross-reactivity of TDXSP with cyclosporine metabolites M1 (23%) or M17 (12%) was greater than for INCSP (15% and 5%, respectively) or INCTDX (22% and 4%, respectively), but the converse was true with M21 (2% for TDXSP vs 4% and 8%, respectively). Some overestimation of cyclosporine whole-blood concentrations (relative to INCTDX results) may be detected with either the TDXSP (because of cross-reactivity with metabolites) or the INCSP assays (probably because of matrix effects). The similar magnitude of these overestimations suggests that alternative factors such as speed, precision, and cost may influence which method one selects for use in routine monitoring.


Preparation and properties of plate-like titanate (PLT)/calcia-doped ceria (CDC) composites by sol-gel coating method.
In order to obtain UV-shielding materials with good comfort, higher safety and effective UV-shielding ability, lepidocrocite type plate-like titanate (K(0.8)Li(0.27)Ti(1.73)O(4), donated as: PLT)/calcia-doped ceria (donated as: CDC) composites were synthesized by a sol-gel method. After dissolving Ce(NO(3))(3).6H(2)O and Ca(NO(3))(2).4H(2)O into absolute ethanol at 40 degrees C, glacial acetic acid (HAc) and PLT particles dispersed into absolute ethanol were added. Then, the solution was heated at 60 degrees C to get gel-like substance. This gel was dried in a vacuum oven at 333 K for 5 h, and then, the product was collected and ground in an agate mortar followed by calcination at 1073 K for 2 h to form PLT/CDC composites. By optimization, 20 mass% of CDC was coated by one operation. PLT/CDC composites with higher CDC content were obtained by repeating the coating process. The morphology, catalytic activity for the oxidation of organic material, UV-shielding ability and dynamic friction coefficient of as-obtained PLT/CDC composites were characterized. As a result, broad-spectrum UV-shielding composite materials with good comfort and low oxidation catalytic activity were successfully synthesized.


Methods of recording and analysing cough sounds.
Efforts have been directed to evolve a computerized system for acquisition and multi-dimensional analysis of the cough sound. The system consists of a PC-AT486 computer with an ADC board having 12 bit resolution. The audio cough sound is acquired using a sensitive miniature microphone at a sampling rate of 8 kHz in the computer and simultaneously recorded in real time using a digital audio tape recorder which also serves as a back up. Analysis of the cough sound is done in time and frequency domains using the digitized data which provide numerical values for key parameters like cough counts, bouts, their intensity and latency. In addition, the duration of each event and cough patterns provide a unique tool which allows objective evaluation of antitussive and expectorant drugs. Both on-line and off-line checks ensure error-free performance over long periods of time. The entire system has been evaluated for sensitivity, accuracy, precision and reliability. Successful use of this system in clinical studies has established what perhaps is the first integrated approach for the objective evaluation of cough.


Caring for survivors of breast cancer: perspective of the primary care physician.
Increasing numbers of women are surviving breast cancer, and survivorship care is becoming more complex. Primary care physicians provide care for most survivors of breast cancer in the Canadian province of British Columbia. The present study offers insight into the confidence of primary care physicians in their abilities to provide such care. It also explores potential ways to assist those providers in enhancing this aspect of their practice. A questionnaire was mailed to 1000 primary care physicians caring for survivors of breast cancer. The questionnaire explored the perspectives of the responding physicians on their ability to manage various aspects of survivorship care for breast cancer patients, identified preferences for the content and format of communication from oncologists at the time of transition from active oncology treatment to survivorship, and determined the means most commonly used to obtain knowledge about breast cancer. This 1-page, 31-item checkbox and open-answer questionnaire assessed the perceptions of primary care physicians about the care of breast cancer survivors after completion of active treatment and their personal preferences for resources providing information about breast cancer. The questionnaire response rate was 59%. Primary care physicians reported being most confident in screening for recurrence and managing patient anxiety; they were least confident in managing lymphedema and providing psychosocial counselling. Compared with physicians following fewer survivors of breast cancer, those who followed more breast cancer survivors had higher confidence in managing the biomedical aspects of follow-up and in providing counselling about nutrition and exercise. Most physicians found discharge letters from oncologists to be useful. Point-form discharge information was preferred by 43%; detailed description, by 19%; and both formats, by 38%. The most useful information items identified for inclusion in a discharge letter were a diagnosis and treatment summary and the recommended surveillance and endocrine therapy. Continuing medical education events and online resources were the means most commonly used to obtain knowledge about breast cancer. Primary care physicians who provide follow-up for survivors of breast cancer report that they are confident in managing care and satisfied with discharge letters containing a diagnosis and treatment summary, and recommendations for surveillance and endocrine treatment. At the time of patient discharge, additional information about common medical and psychosocial issues in this patient population would be useful to primary care physicians. Preferred means to access current breast cancer information include continuing medical education events and online resources.


Isoniazid pharmacokinetic studies of the 1960s: considering a higher isoniazid dose in childhood tuberculosis.
Isoniazid (INH) is one of the most important drugs for the treatment of tuberculosis (TB). In the current international recommendations there is still disagreement on the optimal dosage of INH in childhood TB. This paper presents data from 2 studies, one performed in 1960 and the other in 1961, investigating INH serum levels in children of different age groups, not yet presented internationally. Doses were calculated according to bodyweight (BW) as well as according to body surface area (BSA). In the first study, INH serum levels at different time points in children of different age groups were determined after oral INH administration at 5 mg/kg BW. In the second study, INH serum levels were measured once, 4 h after subcutaneous application of 5 mg/kg BW and once, 4 h after subcutaneous application of INH 200 mg/m(2) BSA 1 week later. These data was compared to adult data on INH collected prior to these studies. After application of 5 mg/kg BW oral dose, INH serum levels were much lower in children than in adults at all time points, especially in children younger than 8 y. In contrast, after dosing according to 200 mg/m(2) BSA, similar serum levels were achieved in children and adults. Dose recommendations of INH 5 mg/kg BW in childhood TB lead to lower serum concentrations than those recommended for adults. In children, it appears to be more appropriate to calculate the INH dose on the basis of body surface area rather than bodyweight.


Adverse dermatological reactions in rheumatoid arthritis patients treated with etanercept, an anti-TNFalpha drug.
Etanercept is an anti-TNF drug with marked efficacy in inflammatory arthritis. This review addresses dermatological side effects that have been encountered in our 85 patients on the drug for rheumatoid arthritis, and reviews other reported cutaneous adverse events. Injection site reactions are common and usually self-limiting. We and others have encountered patients with recall site reactions where the four rotated injection sites simultaneously develop a hypersensitivity reaction. In all cases, the rash has responded to antihistamines and the etanercept was thereby continued. Other injection site reactions include discoid lupus and cutaneous vasculitis that respond to cessation of treatment and appropriate therapy. Skin reactions more distant from the injection site are also reviewed, with erythema nodosum, widespread lupus rashes, infections and skin tumours summarised. A patient who developed a purpuric rash at the site of last injection with a drug induced worsening of thrombocytopaenia is described. Although the therapeutic advantages of etanercept outweigh the side effects, clinicians need to be aware of the adverse reactions of these drugs with their increasing use.


[Techniques and principles of histological diagnosis in osteopathies. Review and report of personal experience].
Histological examination of bone samples from osteopathic patients with subsequent histomorphometric evaluations needs procedures a bit different from those of bioptic routine. They are introduced and summarized according to author's experience. A complete examination necessitates usage of technique for undecalcified samples after previous administering of tetracycline and of a sort of histomorphometric procedure. Routine diagnosis will manage even with decalcified samples supposing they were silver impregnated before decalcification; tetracycline as well as some metals (e.g. aluminium and iron) deposited in the bone will be eluted during decalcification. There are presented definitions and mean values of basic parameters evaluated in histomorphometric analysis.


Microsimulation of an educational attainment register to predict future record linkage quality.
Population wide educational attainment registers are necessary for educational planning and research. Regular linking of databases is needed to build and update such a register. Without availability of unique national identification numbers, record linkage must be based on quasi-identifiers such as name, date of birth and sex. However, the data protection principle of data minimization aims to minimize the set of identifiers in databases. Therefore, the German Federal Ministry of Research and Education commissioned a study to inform legislation on the minimum set of identifiers required for a national educational register. To justify our recommendations empirically, we implemented a microsimulation of about 20 million people. The simulated register accumulates changes and errors in identifiers due to migration, regional mobility, marriage, school career and mortality, thereby allowing the study of errors on longitudinal datasets. Updated records were linked yearly to the simulated register using several linkage methods. Clear-text methods as well as privacy-preserving (PPRL) methods were compared. The results indicate linkage bias if only the primary identifiers are available in the register. More detailed identifiers, including place of birth, are required to minimize linkage bias. The amount of information available to identify a person for matching is more critical for linkage quality than the record linkage method applied. Differences in linkage quality between the best procedures (probabilistic linkage and multiple matchkeys) are minor. Microsimulation is a valuable tool for designing record linkage procedures. By modelling the processes resulting in changes or errors in quasi-identifiers, predicting data quality to be expected after the implementation of a register seems possible.


Post Chikungunya Fever and Post COVID-19 Bilateral Pedal Edema: A Case Report.
An 86-year-old male presented with fever and joint pain for seven days. Clinical features were suggestive of chikungunya fever, but reverse transcription-polymerase chain reaction (RT-PCR) was negative. After ruling out the differentials, the patient was clinically diagnosed with chikungunya fever. Chikungunya IgG antibody was positive two months after the onset of symptoms. He had a history of asymptomatic coronavirus disease (COVID-19) infection two months ago. About 20 days after his first symptom, he developed bipedal edema, refractory to diuretics. All other causes of pedal edema, including heart failure, renal failure, and liver failure, were ruled out. The bipedal edema was managed conservatively with compression bandages. Only a few case reports and studies on limb edema as a symptom post chikungunya fever have been published up to this point. Furthermore, it is difficult to say whether his COVID-19 infection is linked to the edema.


Appearance of white blood cells in the cerebrospinal fluid of rats following intravenous injection of lipopolysaccharide.
Intravenous injection of lipopolysaccharides (LPS), even in very low amounts (5 micrograms), leads to the appearance of white blood cells (WBC) in rat cerebrospinal fluid (CSF). The number of WBC is dependent on either dose of LPS or time of injection. The population of WBC consists of monocytes, granulocytes and lymphocytes, while red blood cells are not detectable. These findings support the pathogenetic role which LPS may play in the course of bacterial meningitis mostly in terms of pleocytosis and raised protein content in the CSF.


Pak-India collaborations in health: insights and way forward.
Commonalities abound varied health challenges confronting Pakistan and India. Some of these warrant joint collaborative solutions. This study presents existing health collaborations by mapping out active connections between the countries, through a literature review and clinical and public health professionals' interviews. It reveals that a diversity of practices exist beyond the usual notions of 'collaboration' usually depicted in the literature. Outcomes from such initiatives included enhanced learning and exchanges of information and research across various communities and contexts. In various adoptions of the term, contextualisation within and between countries and amongst particular communities is cited as important. Travel and mobility restriction emerged as one key issue that hampers and discourages collaborations. Key lessons conveyed by the participants included an enabling environment, missing on both sides of the border. Opportunities and recommendations are presented to address the obstacles that discourage cross-border dialogue and to enhance collaborations between the two countries.


Optical observation of cell sonoporation with low intensity ultrasound.
Sonoporation is a promising drug delivery technique with great potential in medicine. However, its applications have been limited mostly by the lack of understanding its underlying biophysical mechanism, partly due to the inadequacy of the existing models for coupling with highly sensitive imaging techniques to directly observe the actual precursor events of cell-microbubble interaction under low intensity ultrasound. Here, we introduce a new in vitro method utilizing capillary-microgripping system and micro-transducer to achieve maximum level of experimental flexibility for capturing real time highly magnified images of cell-microbubble interaction, hitherto unseen in this context. Insonation of isolated single cells and microbubbles parallel with high speed microphotography and fluorescence microscopy allowed us to identify dynamic responses of cell-membrane/microbubble in correlation with sonoporation. Our results showed that bubble motion and linear oscillation in close contact with the cell membrane can cause local deformation and transient porosity in the cell membrane without rupturing it. This method can also be used as an in situ gene/drug delivery system of targeted cells for non-invasive clinical applications.


Teaching Replication.
Replication is held as the gold standard for ensuring the reliability of published scientific literature. But conducting direct replications is expensive, time-consuming, and unrewarded under current publication practices. So who will do them? The authors argue that students in laboratory classes should replicate recent findings as part of their training in experimental methods. In their own courses, the authors have found that replicating cutting-edge results is exciting and fun; it gives students the opportunity to make real scientific contributions (provided supervision is appropriate); and it provides object lessons about the scientific process, the importance of reporting standards, and the value of openness.


Phenotypic plasticity and water flux rates of Citrus root orders under salinity.
Knowledge about the root system structure and the uptake efficiency of root orders is critical to understand the adaptive plasticity of plants towards salt stress. Thus, this study describes the phenological and physiological plasticity of Citrus volkameriana rootstocks under severe NaCl stress on the level of root orders. Phenotypic root traits known to influence uptake processes, for example frequency of root orders, specific root area, cortical thickness, and xylem traits, did not change homogeneously throughout the root system, but changes after 6 months under 90 mM NaCl stress were root order specific. Chloride accumulation significantly increased with decreasing root order, and the Cl(-) concentration in lower root orders exceeded those in leaves. Water flux densities of first-order roots decreased to <20% under salinity and did not recover after stress release. The water flux densities of higher root orders changed marginally under salinity and increased 2- to 6-fold in second and third root orders after short-term stress release. Changes in root order frequency, morphology, and anatomy indicate rapid and major modification of C. volkameriana root systems under salt stress. Reduced water uptake under salinity was related to changes of water flux densities among root orders and to reduced root surface areas. The importance of root orders for water uptake changed under salinity from root tips towards higher root orders. The root order-specific changes reflect differences in vulnerability (indicated by the salt accumulation) and ontogenetic status, and point to functional differences among root orders under high salinity.


[DNA papillomavirus detection in head and neck benign proliferative lesions].
In a retrospective study, human papillomavirus (HPV) (6/11, 16 and 18 types) were tested using polymerase chain reaction (PCR), in stored formalin-fixed, paraffin-embedded tissue sections, from 36 head and neck adult papillomata. The results, only 20 percent of positive cases, are non consistent with the role of the HPV infection in the etiology of head and neck papillomata in adult patients. However we detect HPV-18 positivity in papillomata with dysplasia.


Transfusion of Human Platelets Treated with Mirasol Pathogen Reduction Technology Does Not Induce Acute Lung Injury in Mice.
Pathogen reduction technology (PRT) has been developed in an effort to make the blood supply safer, but there is controversy as to whether it may induce structural or functional changes to platelets that could lead to acute lung injury after transfusion. In this study, we used a commercial PRT system to treat human platelets that were then transfused into immunodeficient mice, and the development of acute lung injury was determined. P-selectin expression was higher in the Mirasol PRT-treated platelets compared to control platelets on storage day 5, but not storage day 1. Transfusion of control vs. Mirasol PRT-treated platelets (day 5 of storage, 109 platelets per mouse) into NOD/SCID mice did not result in lung injury, however transfusion of storage day 5 platelets treated with thrombin receptor-activating peptide increased both extravascular lung water and lung vascular permeability. Transfusion of day 1 platelets did not produce lung injury in any group, and LPS priming 24 hours before transfusion had no effect on lung injury. In a model of transfusion-related acute lung injury, NOD/SCID mice were susceptible to acute lung injury when challenged with H-2Kd monoclonal antibody vs. isotype control antibody. Using lung intravital microscopy, we did not detect a difference in the dynamic retention of platelets in the lung circulation in control vs. Mirasol PRT-treated groups. In conclusion, Mirasol PRT produced an increase in P-selectin expression that is storage-dependent, but transfusion of human platelets treated with Mirasol PRT into immunodeficient mice did not result in greater platelet retention in the lungs or the development of acute lung injury.


Continuous Manufacturing and Molecular Modeling of Pharmaceutical Amorphous Solid Dispersions.
Amorphous solid dispersions enhance solubility and oral bioavailability of poorly water-soluble drugs. The escalating number of drugs with poor aqueous solubility, poor dissolution, and poor oral bioavailability is an unresolved problem that requires adequate interventions. This review article highlights recent solubility and bioavailability enhancement advances using amorphous solid dispersions (ASDs). The review also highlights the mechanism of enhanced dissolution and the challenges faced by ASD-based products, such as stability and scale-up. The role of process analytical technology (PAT) supporting continuous manufacturing is highlighted. Accurately predicting interactions between the drug and polymeric carrier requires long experimental screening methods, and this is a space where computational tools hold significant potential. Recent advancements in data science, computational tools, and easy access to high-end computation power are set to accelerate ASD-based research. Hence, particular emphasis has been given to molecular modeling techniques that can address some of the unsolved questions related to ASDs. With the advancement in PAT tools and artificial intelligence, there is an increasing interest in the continuous manufacturing of pharmaceuticals. ASDs are a suitable option for continuous manufacturing, as production of a drug product from an ASD by direct compression is a reality, where the addition of multiple excipients is easy to avoid. Significant attention is necessary for ongoing clinical studies based on ASDs, which is paving the way for the approval of many new ASDs and their introduction into the market.


Respiratory response to skin incision during anaesthesia with infusions of propofol and alfentanil.
The ventilatory response to skin incision during anaesthesia with enflurane is an increase in tidal volume without a change in frequency. As opioids affect respiratory frequency and also affect the processing of pain, we investigated if the breathing response to a painful stimulus could be different during anaesthesia using opioids. We studied 12 patients during anaesthesia with target-controlled infusions of propofol (plasma target concentration 4-6 microg ml(-1)) and alfentanil (plasma target concentration 40-60 ng ml(-1)), having varicose vein surgery. After the initial skin incision, tidal volume increased promptly by 17 (4, 81)% (median, quartile values) (P<0.01). Respiratory frequency changed variably with no significant change overall [median change 2 (-8, +50)%]. The duration of inspiration was virtually unaltered, and the duration of expiration decreased gradually by 5 (-7, 32)%. Patients who showed more response also showed more change in tidal volume, so that there was a significant relationship between increased inspiratory flow rate and reduced expiratory time (P<0.05). During opioid anaesthesia, the mechanism of ventilatory increase after stimulation involves changes in both drive and timing of breathing. This pattern of response does not resemble the changes seen during anaesthesia with potent volatile agents.


Chrysophiles versus chrysophobes: the white asbestos controversy, 1950s-2004.
In the first half of the twentieth century, asbestos was a controversial mineral because of its association with asbestosis and asbestos-related lung cancer. It has proved no less so since the 1960s, when another asbestos cancer, mesothelioma, was identified. Mesothelioma appeared to be more strongly linked with blue asbestos (crocidolite) than with the other asbestos varieties, brown (amosite) and white (chrysotile). This finding triggered a fierce debate between "chrysophiles" (those who declared chrysotile innocuous) and "chrysophobes" (those who believed it was a mortal hazard). This essay attempts the first history of the chrysotile controversy, which shows that a scientific consensus on the safety of white asbestos was very slow to emerge. This was only partly due to the complexities of scientific research. Political, economic, and social factors have militated against a speedy resolution of the debate, facilitating the continued production and use of asbestos in the developing world.


Comparative study of the conditions required to image live human epithelial and fibroblast cells using atomic force microscopy.
Successful imaging of living human cells using atomic force microscopy (AFM) is influenced by many variables including cell culture conditions, cell morphology, surface topography, scan parameters, and cantilever choice. In this study, these variables were investigated while imaging two morphologically distinct human cell lines, namely LL24 (fibroblasts) and NCI H727 (epithelial) cells. The cell types used in this study were found to require different parameter settings to produce images showing the greatest detail. In contact mode, optimal loading forces ranged between 2-2.8 x 10(-9) and 0.1-0.7 x 10(-9) (N) for LL24 and NCI H727 cells respectively. In tapping (AC) mode, images of LL24 cells were obtained using cantilevers with a spring constant of at least 0.32 N/m, while NCI H727 cells required a greater spring constant of at least 0.58 N/m. To obtain tapping mode images, cantilevers needed to be tuned to resonate at higher frequencies than their resonance frequencies to obtain images. For NCI H727 cells, contact mode imaging produced the clearest images. For LL24 cells, contact and tapping mode AFM produced images of comparable quality. Overall, this study shows that cells with different morphologies and surface topography require different scanning approaches and optimal conditions must be determined empirically to achieve images of high quality.


Direct temperature measurement.
Hyperthermia has little hope of progressing as a clinical modality without accurate assessment of the temperature distributions obtained. At the present time only direct, invasive temperature-measuring techniques are possible, posing severe limitations. Established techniques for clinical temperature measurement have developed over the past few years, and for both ultrasound and electromagnetic hyperthermia it is possible to get temperature-time profiles at a large number of spatial points. Position uncertainty, thermal conduction smearing, and artifactual heating limit the accuracy to about 0.2 degrees (electromagnetic) or 0.5 degrees (ultrasound), but this is probably less of a hindrance than the inadequate percentage of tumor and normal tissue volume for which achieved temperatures can be documented.


Nck2 promotes human melanoma cell proliferation, migration and invasion in vitro and primary melanoma-derived tumor growth in vivo.
Nck1 and Nck2 adaptor proteins are involved in signaling pathways mediating proliferation, cytoskeleton organization and integrated stress response. Overexpression of Nck1 in fibroblasts has been shown to be oncogenic. Through the years this concept has been challenged and the consensus is now that overexpression of either Nck cooperates with strong oncogenes to transform cells. Therefore, variations in Nck expression levels in transformed cells could endorse cancer progression. Expression of Nck1 and Nck2 proteins in various cancer cell lines at different stages of progression were analyzed by western blots. We created human primary melanoma cell lines overexpressing GFP-Nck2 and investigated their ability to proliferate along with metastatic characteristics such as migration and invasion. By western blot analysis, we compared levels of proteins phosphorylated on tyrosine as well as cadherins and integrins in human melanoma cells overexpressing or not Nck2. Finally, in mice we assessed tumor growth rate of human melanoma cells expressing increasing levels of Nck2. We found that expression of Nck2 is consistently increased in various metastatic cancer cell lines compared with primary counterparts. Particularly, we observed significant higher levels of Nck2 protein and mRNA, as opposed to no change in Nck1, in human metastatic melanoma cell lines compared with non-metastatic melanoma and normal melanocytes. We demonstrated the involvement of Nck2 in proliferation, migration and invasion in human melanoma cells. Moreover, we discovered that Nck2 overexpression in human primary melanoma cells correlates with higher levels of proteins phosphorylated on tyrosine residues, assembly of Nck2-dependent pY-proteins-containing molecular complexes and downregulation of cadherins and integrins. Importantly, we uncovered that injection of Nck2-overexpressing human primary melanoma cells into mice increases melanoma-derived tumor growth rate. Collectively, our data indicate that Nck2 effectively influences human melanoma phenotype progression. At the molecular level, we propose that Nck2 in human primary melanoma promotes the formation of molecular complexes regulating proliferation and actin cytoskeleton dynamics by modulating kinases or phosphatases activities that results in increased levels of proteins phosphorylated on tyrosine residues. This study provides new insights regarding cancer progression that could impact on the therapeutic strategies targeting cancer.


System Issues Leading to "Found-on-Floor" Incidents: A Multi-Incident Analysis.
Although attention to patient safety issues in the home care setting is growing, few studies have highlighted health system-level concerns that contribute to patient safety incidents in the home. Found-on-floor (FOF) incidents are a key patient safety issue that is unique to the home care setting and highlights a number of opportunities for system-level improvements to drive enhanced patient safety. We completed a multi-incident analysis of FOF incidents documented in the electronic record system of a home health care agency in Toronto, Canada, for the course of 1 year between January 2012 and February 2013. Length of stay (LOS) was identified as the cross-cutting theme, illustrating the following 3 key issues: (1) in the short LOS group, a lack of information continuity led to missed fall risk information by home care professionals; (2) in the medium LOS group, a lack of personal support worker/carer training in fall prevention led to inadequate fall prevention activity; and (3) in the long LOS group, a lack of accountability policy at a system level led to a lack of fall risk assessment follow-up. Our study suggests that considering LOS in the home care sector helps expose key system-level issues enabling safety incidents such as FOF to occur. Our multi-incident analysis identified a number of opportunities for system-level changes that might improve fall prevention practice and reduce the likelihood of FOF incidents in the home. Specifically, investment in electronic health records that are functional across the continuum of care, further research and understanding of the training and skills of personal support workers, and enhanced incentives or more punitive approaches (depending on the circumstances) to ensure accountability in home safety will strengthen the home care sector and help prevent FOF incidents among older people.


Consumption of sexual dialogue and content on television and adolescent sexual outcomes: multiethnic findings.
The purposes of this study were to examine group differences in sexual media consumption and to explore how well adolescents' sexual attitudes and behavior can be explained by viewing of sexually suggestive dialogue (SD) and explicit sexual content (SC) in television media. Participants were 473 male and female high school adolescents who were racially, economically, and age diverse. Television viewing was coded for SD and SC. Both length of time spent watching SD and SC and explicitness of the SD and SC to which adolescents were exposed were factored into the coding scheme. In this sample, SD and SC consumption varied by subgroup and explained variance in some sexual attitudes and behavior variables but not others, and in some demographic subgroups but not others.


Minority status, consumer outcomes, and service inputs in four States.
Data from the Center for Outcome Analysis were subjected to independent secondary analysis involving comparisons by ethnic group of eight indicators of service quality for users of adult developmental disability services in four states. Ethnic group membership had very limited or no association with the consumer outcomes and service inputs evaluated. Where significant ethnic group differences were found, they were small, and there was no consistent pattern of a particular ethnic group doing better. These findings may relate to the substantial influence of developmental disability services in the lives of service recipients and to the effect of disability itself, in that adaptive behavior was strongly related to most consumer outcomes.


Mental retardation in amaurosis congenita of Leber.
A group of 229 patients with Leber's congenital amaurosis (ACL) was investigated for associated defects. We especially looked for the occurrence of mental retardation because the literature gives varying frequencies for this association. A percentage of 19.8% was found. This finding has consequences for genetic counseling. Special attention was given to how frequently sibling pairs occurred in which one patient was mentally retarded whereas the other functioned normally. We found 11 sibling pairs that were discordant with regard to their mental state. This observation proves that mental retardation could be one variable expression of ACL.


Conducting-insulating transition in adiabatic memristive networks.
The development of neuromorphic systems based on memristive elements-resistors with memory-requires a fundamental understanding of their collective dynamics when organized in networks. Here, we study an experimentally inspired model of two-dimensional disordered memristive networks subject to a slowly ramped voltage and show that they undergo a discontinuous transition in the conductivity for sufficiently high values of memory, as quantified by the memristive ON-OFF ratio. We investigate the consequences of this transition for the memristive current-voltage characteristics both through simulation and theory, and demonstrate the role of current-voltage duality in relating forward and reverse switching processes. Our work sheds considerable light on the statistical properties of memristive networks that are presently studied both for unconventional computing and as models of neural networks.


Potential Chemopreventive Role of Boldine Against Hepatocellular Carcinoma via Modulation of Cell Cycle Proteins in Rat Model.
To evaluate the chemopreventive potential of boldine against diethylnitrosamine (DEN) induced hepatocellular carcinoma (HCC) in Wistar albino rats. Boldine is an alkaloid isolated from Peumus boldus. The primary active constituents of boldine exhibited several potential medicinal properties. The present study was evaluated to explore the chemopreventive agent of boldine on anti-proliferative efficacy against diethylnitrosamine (DEN) induced hepatocellular carcinoma (HCC) in Wistar albino rats. The effect of boldine on cellular proliferative markers, i.e., PCNA and Ki67on hepatocellular carcinoma rats was determined by immuno expression study. Liver marker enzymes, tumor biomarker, oxidative stress markers, antioxidant status, and xenobiotic phase I and II enzymes in HCC rats were analyzed. Moreover, cell cycle proteins, i.e., p21Cip1/Kip1and p27 Cip1/Kip1, Cyclin D1, CDK 4, Cyclin E1, and CDK 2 were investigated using immuno expression analysis. Treatment of boldine protected the liver against reactive oxygen species such as hydrogen peroxide, superoxide, protein carbonyl, and lipid peroxide during hepatocarcinogenesis by boosted antioxidants-superoxide dismutase (SOD), catalase (CAT). Boldine caused a substantial enhanced detoxification process by moderating phase I and II xenobiotic-metabolizing enzymes. Besides, the study found that boldine significantly inhibited the cellular proliferative markers like PCNA and Ki67 and regulated the specific cell cycle-associated proteins by up-regulated expression of p21Cip1/Kip1and p27 Cip1/Kip1 and down-regulated expression of Cyclin D1, CDK 4, Cyclin E1, and CDK 2. Our data manifests the anti-proliferative effect of boldine, which negatively modulates cellular proliferation and regulates cell cycle by protecting the cell from reactive oxygen species (ROS), suggesting that boldine establishes it as a chemopreventive agent in diethylnitrosamine-induced hepatocarcinogenesis in rats.


Autograft transfer from the ipsilateral femoral condyle in depressed tibial plateau fractures.
The rationale for operative treatment of depressed tibial plateau fractures is anatomic reduction, stable fixation and grafting. Grafting options include autogenous bone graft or bone substitutes. The autograft group included 18 patients with depressed tibial plateau fractures treated with autogenous bone grafting from the ipsilateral femoral condyle following open reduction and internal fixation. According to Schatzker classification, there were 9 type II, 4 type III, 2 type IV and 3 type V lesions. The average time to union and the hospital charges were compared with the bone substitute group. The latter included 17 patients who had an excellent outcome following treatment of split and/or depressed lateral plateau fractures, using a similar surgical technique but grafting with bone substitutes (allografts). Excellent clinical and radiological results were detected in the autograft group after an average follow-up of 28 months (range 12-37). The average time to union in the autograft group was 14 weeks (range 12-16), while in the bone substitute group it was 18 weeks (range 16-20). The mean total cost was 1276 Euros for the autograft group and 2978 Euros for the bone substitute group. The use of autogenous graft from the ipsilateral femoral condyle following open reduction and internal fixation of depressed tibial plateau fractures provided enough bone to maintain the height of the tibial plateau and was not associated with any donor site morbidity. Using this method, the surgical time was not significantly elongated and the rehabilitation was not affected. It also exhibited faster fracture healing without postoperative loss of reduction and it was less expensive than the use of bone substitutes.


Current use and opinions regarding human patient simulators in nursing education: an international survey.
The human patient simulator (HPS) has recently been introduced as an adjunct technology in nursing education. An international survey of nursing schools and simulation centers that collaborate with nursing schools and have purchased a Medical Education Technologies, Inc. (METI) HPS was undertaken in 2002. Thirty-four schools of nursing (18 based in universities and 16 based in community colleges) and six simulation centers participated in the survey. Information gathered from the survey and reported on in this article includes curricular use, faculty time and use, student opinions, evaluation, and other uses of the HPS, specifically in research and continuing education. The results provide a foundation for early use of the HPS in nursing education at all levels.


Parallel response selection disrupts sequence learning under dual-task conditions.
Some studies suggest that dual-task processing impairs sequence learning; others suggest it does not. The reason for this discrepancy remains obscure. It may have to do with the dual-task procedure often used. Many dual-task sequence learning studies pair the serial reaction time (SRT) task with a tone-counting secondary task. The tone-counting task, however, is not ideal for studying the cognitive processes involved in sequence learning. The present experiments sought to identify the nature of the interference responsible for disrupting sequence learning in dual-task situations using more tractable dual-task procedures. Experiments 1 and 2 showed that parallel-interfering central processing disrupts sequence learning. Experiment 3 used a novel combination of the SRT task as the secondary task in a psychological refractory period procedure. It showed that SRT task performance can be disrupted without disrupting sequence learning when that disruption involves a response-selection bottleneck rather than parallel response selection. Together, these results suggest that it is the overlap of central processes involved in successfully performing the 2 tasks concurrently that leads to learning deficits in dual-task sequence learning.


Anti-CD45RB and donor-specific spleen cells transfusion inhibition allograft skin rejection mediated by memory T cells.
Donor-reactive memory T (Tm)cells mediate accelerated rejection, which is known as a barrier to the survival of transplanted organs. Selective interference with the anti-CD45RB monoclonal antibody (α-CD45RB) reliably induces donor-specific tolerance. In this study, pre-sensitization to female C57BL/6 mice with the skin of female BLAB/c mice generated a large number of Tm cells and resulted in rapid rejection of the secondly transplanted allografts. α-CD45RB did induce the tolerance to skin allograft primarily transplanted but failed to induce tolerance in the pre-sensitized mice. Donor-specific spleen cell transfusion (DST) alone also failed to induce the tolerance in the pre-sensitized recipients. Interestingly, combination of α-CD45RB with DST inhibited the rejection induced by memory T cells in the pre-sensitized mice. CD25+ T-cell depletion in α-CD45RB combined with DST therapy recipients could prevent skin allograft tolerance from establishing. In addition, adoptive transfer of donor-primed memory T cells into the tolerant recipients markedly broke the established tolerance. Our findings indicate that α-CD45RB and DST can synergistically inhibit the accelerated rejection mediated by memory T cells and induce long-term skin allograft acceptance in mice.


Placental laser surgery for severe previable feto-fetal transfusion syndrome in triplet gestation.
Information on feto-fetal transfusion syndrome (FFTS) in higher-order multifetal gestation is limited. We report outcomes of 10 triplet pregnancies treated by fetoscopic laser occlusion of the chorioangiopagous vessels (FLOC). The study period was August 1992 to August 2008. Inclusion criteria were gestational age < or =25 weeks and ultrasound confirmation of monochorionicity in at least one twin set and FFTS. Treatment included FLOC, exit amnioreduction, and cerclage when indicated. Hospital records, placental pathology, neonatal course, and long term follow-up of the mother and infants were reviewed. There were eight triamnionic dichorionic and two triamnionic monochorionic triplets. Mean maternal age was 29.8 years, and five conceived following in vitro fertilization. FFTS stage at treatment was > or =II in all cases, at a mean gestational age 20.9 +/- 2.2 weeks. Two patients required immediate rescue cerclage, and all 10 had hypoproteinemia and anemia. Mean age at delivery was 31.2 +/- 3.4 weeks, with a mean birth weight 1568.4 +/- 498 g for the live-born fetuses. Twenty-three (77%) fetuses survived, with at least one fetus surviving in 9 (90%) cases. Cerebral ultrasound imaging and neurological examination were normal in all neonates, and clinical follow-up has remained normal at 67.5 +/- 56 months for the group. FLOC is feasible in dichorionic and monochorionic triplet pregnancy complicated by FFTS. Outcomes are comparable to our experience with twins, namely improved perinatal survival and neonatal morbidity when compared with alternative treatments.


The use of hydrogen peroxide to visualize tattoos obscured by decomposition and mummification.
Tattoos are distinctive, potentially important acquired identifying features that last for the life of the bearer, and persist into the postmortem period. However, the accumulation of decompositional pigments in the skin and subcutaneum will obscure tattoo designs. By treating the area with 3% hydrogen peroxide, the dark red-black decomposition products are temporarily removed, allowing underlying tattoos to be located, and photographed for identification purposes.


Species difference in the inhibitory potentials of non-steroidal anti-inflammatory drugs on the hepatic sulfation and glucuronidation of bioactive flavonoids: differential observations among common inhibition parameters.
1. This study elucidated the species differences between rats and humans in the inhibitory potential of drugs against sulfation and glucuronidation, and whether such differences depend on the inhibition parameter adopted. 2. With 14 non-steroidal anti-inflammatory drugs (NSAIDs) as model inhibitors and three flavanoids baicalein, wogonin and oroxylin A as model substrates, three common inhibition parameters percentage of control, IC50 and Ki were determined in rat liver cytosols (RLCs), human liver cytosols (HLCs), rat liver microsomes (RLMs) and human liver microsomes (HLMs). The closeness of the inhibition parameters from rat liver preparations to that from human liver preparations was analyzed by geometric mean fold error (GMFE) and statistical comparisons. 3. The percentage of control in RLC/RLM was not significantly different from that in HLC/HLM, with a GMFE of 0.85 (RLC-HLC) and 1.03 (RLM-HLM); whereas the IC50 and Ki in RLC/RLM were significantly different from that in HLC/HLM. The trend of difference was consistent between IC50 and Ki, where these parameters in RLC and RLM underestimated (GMFE <0.5) and overestimated (GMFE >2) that in HLC and HLM, respectively. 4. In conclusion, the inhibitory potentials of NSAIDs against sulfation and glucuronidation in rats and humans were different and depended on the adopted inhibition parameters.


Cells strongly expressing Ig(kappa) transgenes show clonal recruitment of hypermutation: a role for both MAR and the enhancers.
The V regions of immunoglobulin kappa transgenes are targets for hypermutation in germinal centre B cells. We show by use of modified transgenes that the recruitment of hypermutation is substantially impaired by deletion of the nuclear matrix attachment region (MAR) which flanks the intron-enhancer (Ei). Decreased mutation is also obtained if Ei, the core region of the kappa3'-enhancer (E3') or the E3'-flank are removed individually. A broad correlation between expression and mutation is indicated not only by the fact that the deletions affecting mutation also give reduced transgene expression, but especially by the finding that, within a single mouse, transgene mutation was considerably reduced in germinal centre B cells that poorly expressed the transgene as compared with strongly expressing cells. We also observed that the diminished mutation in transgenes carrying regulatory element deletions was manifested by an increased proportion of B cells in which the transgene had not been targeted at all for mutation rather than in the extent of mutation accumulation once targeted. Since mutations appear to be incorporated stepwise, the results point to a connection between transcription initiation and the clonal recruitment of hypermutation, with hypermutation being more fastidious than transcription in requiring the presence of a full complement of regulatory elements.


Mechanism of impaired beta-adrenoceptor responsiveness in atopic sensitized airway smooth muscle.
Decreased airway relaxation to beta-adrenoceptor stimulation has been hypothesized as a potential mechanism leading to enhanced bronchoconstrictor responsiveness in asthma. In addressing potential mechanisms underlying this phenomenon, the relative contributions of beta-adrenoceptor-coupled transmembrane signaling mechanisms were examined in isolated rabbit tracheal smooth muscle (TSM) passively sensitized with serum from atopic asthmatic patients and in TSM comparably exposed to non-atopic (control) human serum. During half-maximal isometric contraction of the tissues with acetylcholine, relative to control TSM, the sensitized tissues exhibited significant attenuation of both their maximal relaxation (Rmax) and sensitivity (i.e., -log 50% Rmax) to cumulative administration of isoproterenol (P < 0.001) or prostaglandin (PG)E2 (P < 0.001). In contrast, the relaxation responses to forskolin, a diterpene that directly activates adenylate cyclase, were similar in both tissue groups. Extended studies demonstrated that the attenuated relaxation to isoproterenol and PGE2 in sensitized TSM was 1) ablated by pretreatment with the muscarinic M2-receptor antagonists methoctramine (10(-6) M) or gallamine (10(-4) M); 2) also inhibited by pretreatment with pertussis toxin (100 ng/ml), which ADP ribosylates the inhibitory G protein (G(i)) negatively coupled to adenylate cyclase activation; and 3) associated with diminished adenosine 3',5'-cyclic monophosphate accumulation in response to isoproterenol administration. Moreover, based on Western immunoblot analysis, we found that G(i) protein expression was increased in membrane fractions from sensitized TSM, related to enhanced expression of the G(i) alpha 3 subunit. Collectively, these observations provide new evidence that the impaired beta-adrenoceptor-mediated relaxation in atopic sensitized airways is associated with increased muscarinic M2 receptor/G(i) protein-coupled expression and function.


Design of a hybrid ANN multi-objective whale algorithm for suspended sediment load prediction.
There is a need to develop an accurate and reliable model for predicting suspended sediment load (SSL) because of its complexity and difficulty in practice. This is due to the fact that sediment transportation is extremely nonlinear and is directed by numerous parameters such as rainfall, sediment supply, and strength of flow. Thus, this study examined two scenarios to investigate the effectiveness of the artificial neural network (ANN) models and determine the sensitivity of the predictive accuracy of the model to specific input parameters. The first scenario proposed three advanced optimisers-whale algorithm (WA), particle swarm optimization (PSO), and bat algorithm (BA)-for the optimisation of the performance of artificial neural network (ANN) in accurately predicting the suspended sediment load rate at the Goorganrood basin, Iran. In total, 5 different input combinations were examined in various lag days of up to 5 days to make a 1-day-ahead SSL prediction. Scenario 2 introduced a multi-objective (MO) optimisation algorithm that utilises the same inputs from scenario 1 as a way of determining the best combination of inputs. Results from scenario 1 revealed that high accuracy levels were achieved upon utilisation of a hybrid ANN-WA model over the ANN-BA with an RMSE value ranging from 1 to 6%. Furthermore, the ANN-WA model performed better than the ANN-PSO with an accuracy improvement value of 5-20%. Scenario 2 achieved the highest R2 when ANN-MOWA was introduced which shows that hybridisation of the multi-objective algorithm with WA and ANN model significantly improves the accuracy of ANN in predicting the daily suspended sediment load.