Allergens of Schistosoma mansoni. II. Fractionation and characterization of S. mansoni egg allergens.
The interaction of Schistosoma mansoni crude soluble egg antigen (SEA) with IgE antibodies in sera from S. mansoni-infected mice, rats and humans has been studied by the radioallergosorbent test (RAST) and the Prausnitz-Küstner (PK) technique. IgE antibodies recognizing egg antigens were present as early as day 21 after the infection in the mouse sera and day 28 in rat sera. IgE in sera of infected humans reacted with antigenic components in the Mr range 70,000-150,000 and focusing as a broad peak in the pH range 4.5-6.5 as measured by RAST. SDS-PAGE followed by western blotting showed the presence of major components at molecular weights of 117,000 and 35,000-43,000. In the PK test, using mouse sera, components focusing in the alkaline pH range also gave a positive reaction. Most of the allergenic activity was bound by concanavalin A-Sepharose and by wheat germ agglutinin-Ultrogel. IgE in serum from an infected non-permissive host (the Fischer rat) apparently recognized egg-stage-specific allergen as indicated by differences in the time course of the IgE response to egg allergens compared to the adult material. When analyzed by SDS-PAGE and western blotting with day 45-infected rat serum, SEA showed some qualitative and quantitative differences to adult worm antigen. Molecules at molecular weights between 25,000 and 30,000 and at about 43,000 in SEA reacted with rat serum IgE and were absent from adult worm antigen. The allergenic similarities between egg and adult worm are discussed.


Effect of chondroitin sulphate on material properties and bone remodelling around hydroxyapatite/collagen composites.
Chondroitin sulphate (CS) has an anti-inflammatory effect and increases the regeneration ability of injured bone. The goal of this study was to characterize the material properties and osteoconductive potency of calcium phosphate bone cements modified with CS. The early interface reaction of cancellous bone to a nanokristalline hydroxyapatite cement containing type I collagen (HA/Coll) without and with CS (HA/Coll/CS) in a rat tibia model was evaluated. Cylindrical implants were inserted press-fit into defect of the tibial head. Six specimens per group were analyzed at 2, 4, 7, 14, and 28 days. HA/Coll/CS composite cylinders showed a 15% increase in compressive strength and by investigations with powder X-ray diffraction more nontransformed cement precursor was found. The microstructures of both types of implants were similar. A significantly higher average number of TRAP positive osteoclasts and ED1 positive mononuclear cells were observed in the interface around HA/Coll/CS implants on day 4 and 7 (p < 0.05). At 28 days the direct bone contact and the percentage of newly formed bone were significantly higher around HA/Coll/CS implants (p < 0.05). The addition of CS appears to enhance bone remodelling and new bone formation around HA/Coll composites in the early stages of bone healing. Possible mechanisms are discussed.


Measurement of the conductance of a hydrogen molecule.
Recent years have shown steady progress towards molecular electronics, in which molecules form basic components such as switches, diodes and electronic mixers. Often, a scanning tunnelling microscope is used to address an individual molecule, although this arrangement does not provide long-term stability. Therefore, metal-molecule-metal links using break-junction devices have also been explored; however, it is difficult to establish unambiguously that a single molecule forms the contact. Here we show that a single hydrogen molecule can form a stable bridge between platinum electrodes. In contrast to results for organic molecules, the bridge has a nearly perfect conductance of one quantum unit, carried by a single channel. The hydrogen bridge represents a simple test system in which to understand fundamental transport properties of single-molecule devices.


[Prognostic value of S-100B protein plasma measurement after cardiac arrest].
S-100B protein is selectively synthesized by glial cells, and is released in biological fluids after acute brain damage. We analyzed initial levels and evolution of plasma S-100B protein concentrations after resuscitated cardiopulmonary arrest (CPA). S-100B levels were determined in 27 subjects at the time of CPA (H0) then 12, 24 and 48 h after resuscitation. Initial levels of S-100B and kinetics revealed that: 1) 95% the of subjects with a concentration of protein S-100B greater than 0.80 microg/L at H0 did not survive; 2) 62% of subjects with a concentration of protein S-100B lower than 0.80 microg/L at H0 survived; 3) 100% of subjects with a protein S-100B level lower than 0.80 microg/L at H0 and whose evolution kinetics of S-100B levels showed a decrease survived; 4) 100% of the subjects whose S-100B levels increased from H12 died. In summary, this study suggests that the threshold of 0.80 microg/L for S-100B plasma levels at H0 could be predictive for the outcome of the CPA, when associated with the kinetic study of S-100B plasma concentration.


o-Alkylselenenylated benzoic acid accesses several sites in serum albumin according to fluorescence studies, Raman spectroscopy and theoretical simulations.
In the circulatory system, serum albumin (SA) is an important transporter of the majority of molecules with biological activity. We focused the current study on the anti-inflammatory compound, o-alkylselenenylated benzoic acid (ALKSEBEA), to determine its ability to access SA. Herein, we employed experimental procedures (fluorescence studies, Raman spectroscopy) and docking study on SA obtained from the Protein Data Bank and key conformers obtained from molecular dynamics simulations. The results show that ALKSEBEA accesses SA using a cooperative behavior according to fluorescence studies. In addition, the Raman results indicate that the ligand binding affects the backbone constituents. These results were confirmed by docking simulations tested on several SA conformers, which showed that ALKSEBEA bound on several sites on SA via π-π or π-cation interactions and that the ligand reaches other binding sites, where aromatic and basic residues as well as the backbone residues are involved.


[The influence of electromagnetic fields on flora and fauna].
This paper presents the influence of natural and artificial electromagnetic fields (EMF) on fauna and flora. The mechanisms of Earth's magnetic field detection and the use of this skill by migratory animals to faultlessly reach the destination of their travel are discussed, as well as the positive effects of electric and magnetic fields on plants relative to their physiology, yielding and health. EMF influence on social insects and animal organisms, including possible DNA damages and DNA repair systems, is presented. The influence of high frequency electromagnetic fields on birds nesting is also discussed.


Management of the eye after iatrogenic facial paralysis.
The aesthetic and functional morbidity associated with facial palsy is significant. Fortunately, corneal exposure and ulceration with the potential for the loss of visual acuity can be minimized by eyelid procedures such as gold weight implantation and horizontal eyelid shortening. Although primarily designed for restoration of eyelid function, these procedures also improve ocular cosmesis. However, uncertainty remains regarding the indications for eyelid surgery: When should surgery be performed, in whom, and which procedure(s)? On the basis of our series of 60 patients evaluated for facial paralysis, guidelines for the management of the paralyzed eyelids after iatrogenic injury to the facial nerve are proposed.


Amphotericin B: from derivatives to covalent targeted conjugates.
This mini-review summarizes the development of the derivatives and conjugates of Amphotericin B (AMB) which have not been clinically applied so far but are therapeutically promising. Effects of chemical modifications of AMB upon biological activities of the resulting derivatives are discussed. The examples presented include variation of functional groups in AMB, covalent conjugates with other molecules, poly(ethylene glycols) and polysaccharides. Possibilities of targeted delivery of AMB are discussed.


Undetectable pregnancy-associated plasma protein-A in antenatal serum Down's syndrome screening: a case of assay interference.
Serum pregnancy-associated plasma protein-A (PAPP-A) is measured in Down's syndrome screening, routinely offered to women in pregnancy. We present the case of an undetectable pregnancy-associated plasma protein-A concentration on the PerkinElmer AutoDELFIA system where immunoassay interference was suspected. Investigations performed, including dilution and recovery studies and antibody-blocking tube incubations, all yielded serum pregnancy-associated plasma protein-A concentrations of <25 mU/L. Pregnancy-associated plasma protein-A was also undetectable on two alternative pregnancy-associated plasma protein-A assays. An experimental manual Delfia procedure suggested the site of interference was between the secondary antibody and the pregnancy-associated plasma protein-A molecule. This case of negative interference in the PerkinElmer pregnancy-associated plasma protein-A assay produced a falsely high Down's syndrome risk that might have led to an unnecessary invasive procedure with the potential for fetal loss. This highlights the need for Down's syndrome screening laboratories to be vigilant to immunoassay interference due to the significant impact of the results on patient decision outcome.


Talin immunogold density increases in sciatic nerve of diabetic rats after nerve growth factor treatment.
Diabetic neuropathy is a debilitating disorder whose causation is poorly understood. Recent studies have shown significant reduction in the activity of nerve growth factor (NGF) and in the amount of talin cytoskeleton protein immunoreactivity in the perineurium in patients with diabetic neuropathy. Since talin is involved in transmembrane connections between extracellular matrix and cytoskeleton, this study investigates the subcellular pattern of talin immunoreactivity and the effect of NGF treatment of diabetic rats on the distribution of talin in the sciatic nerve. Post-embedding immunogold electron microscopy using monoclonal antibody against talin in combination with quantitative procedures was employed to localize talin-like immunoreactivity in the sciatic nerve of normal, diabetic and NGF treated diabetic rats. We found the highest densities of gold particles in the Schwann cells (139.6+/-5.6 particles/microm2) and in the fibroblasts (127.4+/-4.1 particles/microm2). A moderate amount of immunoreactivity was also present in the endothelial cells of vasa nervosa (32.3+/-9.1 particles/microm2). The myelinated and unmyelinated nerve fibers and the extracellular matrix profiles were not labeled (8.7+/-2.1 particles/microm2, 4.2+/-2.2 particles/microm2, 6.1+/-3.2 particles/microm2, 9.5+/-5.3 particles/microm2, respectively). The immunogold localization of talin in diabetic rats was significantly (p<0.001) reduced in Schwann cells (66.3+/-6.5 particles/microm2) and perineurial and epineurial fibroblasts (56.8+/-3.9 particles/microm2). Diabetic rats treated with NGF for 12 weeks showed significant (p<0.005) increase in talin-like immunogold density in Schwann cells and fibroblasts. Talin immunogold density in Schwann cells and fibroblasts increased approximately 68% and 58%, respectively, after NGF treatment. The endothelial cells of endoneurial and epineurial vessel walls showed no significant change in the talin-like immunogold particle density among control, diabetic and NGF treated diabetic animals. These results have shown that the administration of exogenous NGF may be essential for inducing functionally significant regenerative mechanisms in diabetic neuropathy through maintaining the permeability of the barrier properties of the peripheral nerve.


Integrated care in Germany-a stony but necessary road!
German healthcare provides a very comprehensive benefits catalogue, high quality standards, low access barriers and in particular healthcare which is independent from one's income. But at the same time it is one of the most expensive systems in the world. Reasons for the high costs of care are mainly due to the separation of the outpatient, inpatient and rehabilitation sectors, the poor information flow between the service providers and insufficient competition in healthcare provision. In the last 15 years the German government has introduced various reform acts and in doing so has followed a continual path of development: more competition for care concepts between health insurances, more options for the insured and more leeway for players in the various sectors of healthcare. The following article gives an overview of new forms of contracting that have been introduced and provides recommendations for the further development of integrated care in the German healthcare system.


[Stress echocardiography--an evaluation of current status].
Exercise echocardiography, a versatile, noninvasive diagnostic test of left ventricular wall motion performed at rest and under induced stress, enables the cardiologist to detect and assess coronary artery disease. Stress-induced ischemia is thereby expressed as left ventricular regional wall motion abnormality. By using various physical (bicycle or treadmill exercise) and pharmacological (dipyridamole, dobutamine, adenosine) stress inducers, the test provides information about the localization and extent of coronary artery disease in addition to detecting stress-induced coronary insufficiency. As regards diagnostic accuracy in detecting coronary artery disease, stress echocardiography is superior to exercise electrocardiography and, according to the available data, it is comparable to perfusion scintigraphic testing. Studies have demonstrated the clinical value of stress echocardiography in detecting residual stenosis after angioplasty, for diagnosing bypass dysfunction after heart surgery, for preoperative risk assessment in noncardiac surgeries, and for obtaining prognostic information, e.g., after myocardial infarction. Preliminary studies have shown that pharmacological exercise echocardiography is able to identify viable myocardium in the early phases after acute myocardial infarction. Furthermore, it is able to predict the functional success of revascularization in chronic regional left ventricular dysfunction. In addition to the wide range of diagnostic possibilities in coronary artery disease, other notable applications include stress testing for assessment of global left ventricular pump function in patients with aortic regurgitation or cardiomyopathy.


Self-reported psychological distress during the COVID-19 outbreak in Nepal: findings from an online survey.
A lower respiratory tract infection caused by novel coronavirus termed as Corona Virus Disease (COVID-19) was first identified in China and subsequently took the form of pandemic. Studies on disease outbreak in the past and recent COVID-19 outbreak have demonstrated increased psychological distress and adverse impacts on mental health and psychological wellbeing of people. However, the impact of COVID-19 on psychological wellbeing of people in Nepal hasn't been studied adequately. So, this paper aims to report the findings from a social media survey on psychological impacts of COVID-19 in Nepal. Data were collected through social media from 2082 Nepalese respondents between 23rd April, 2020 and 3rd May, 2020. A total of 2014 respondents who were currently residing in Nepal were included in the analysis. The study suggested that half of the respondents suffered from at least one symptom of psychological distress whereas 32% suffered from two or more symptoms of psychological distress such as restlessness, fearfulness, anxiety and worry and sadness in the past 2 weeks preceding the survey date. The findings further suggested that respondents having lower family income, residing in rented room, and participants from province 2 were more likely to suffer from both single and multiple symptoms of psychological distress. The study has shown high prevalence of psychological distress amongst the Nepalese respondents following COVID-19 outbreak. Appropriate mental health and psychosocial support response needs to be instituted to adequately respond to psychological impacts of the epidemic.


Theory and practical application of blood-based renal replacement therapy.
The term renal replacement therapy incorporates three modalities that control or correct biochemical and fluid disturbances of renal failure. Peritoneal dialysis and renal transplantation are two forms of renal replacement therapy that are outside the remit of this article. This review focuses upon the third group which are blood-based and involve direct treatment of a patient's blood in a closed, extracorporeal circuit. They provide renal replacement for end-stage renal failure and during periods of severe acute kidney injury, and also for non-renal indications such as the management of drug overdoses. Blood-based renal replacement therapies are often loosely referred to as 'haemodialysis', although this is only one of a range of treatments. This article outlines the theory and practical applications of these treatments.


An MHV-68 Mutator Phenotype Mutant Virus, Confirmed by CRISPR/Cas9-Mediated Gene Editing of the Viral DNA Polymerase Gene, Shows Reduced Viral Fitness.
Drug resistance studies on human γ-herpesviruses are hampered by the absence of an in vitro system that allows efficient lytic viral replication. Therefore, we employed murine γ-herpesvirus-68 (MHV-68) that efficiently replicates in vitro as a model to study the antiviral resistance of γ-herpesviruses. In this study, we investigated the mechanism of resistance to nucleoside (ganciclovir (GCV)), nucleotide (cidofovir (CDV), HPMP-5azaC, HPMPO-DAPy) and pyrophosphate (foscarnet (PFA)) analogues and the impact of these drug resistance mutations on viral fitness. Viral fitness was determined by dual infection competition assays, where MHV-68 drug-resistant viral clones competed with the wild-type virus in the absence and presence of antivirals. Using next-generation sequencing, the composition of the viral populations was determined at the time of infection and after 5 days of growth. Antiviral drug resistance selection resulted in clones harboring mutations in the viral DNA polymerase (DP), denoted Y383SGCV, Q827RHPMP-5azaC, G302WPFA, K442TPFA, G302W+K442TPFA, C297WHPMPO-DAPy and C981YCDV. Without antiviral pressure, viral clones Q827RHPMP-5azaC, G302WPFA, K442TPFA and G302W+K442TPFA grew equal to the wild-type virus. However, in the presence of antivirals, these mutants had a growth advantage over the wild-type virus that was moderately to very strongly correlated with antiviral resistance. The Y383SGCV mutant was more fit than the wild-type virus with and without antivirals, except in the presence of brivudin. The C297W and C981Y changes were associated with a mutator phenotype and had a severely impaired viral fitness in the absence and presence of antivirals. The mutator phenotype caused by C297W in MHV-68 DP was validated by using a CRISPR/Cas9 genome editing approach.


Social Status and Arginine Vasotocin Neuronal Phenotypes in a Cichlid Fish.
The nonapeptide arginine vasotocin (AVT) and its mammalian homologue arginine vasopressin play a key role in the regulation of social behaviour across vertebrates. In teleost fishes, three AVT neuronal populations have been described in the preoptic area (POA): the parvocellular (pPOA), the magnocellular (mPOA) and the gigantocellular (gPOA). Neurons from each of these areas project both to the pituitary and to other brain regions, where AVT is supposed to regulate neural circuits underlying social behaviour. However, in the fish species studied so far, there is considerable variation in which AVT neuronal populations are involved in behavioural modulation and in the direction of the effect. In this study, the association between AVT neuronal phenotypes and social status was investigated in the Mozambique tilapia (Oreochromis mossambicus). This species is an African female mouth-brooding cichlid fish in which males form breeding aggregations in which dominant males establish territories and subordinate males to act as floaters. With respect to sex differences in AVT neuronal phenotypes, females have a larger number of AVT neurons in the pPOA and mPOA. Within males, AVT appeared associated with social subordination, as indicated by the larger cell body areas of AVT neurons in mPOA and gPOA nuclei of non-territorial males. There were also positive correlations between submissive behaviour and the soma size of AVT cells in all three nuclei and AVT cell number in the mPOA. In summary, the results provide evidence for an involvement of AVT in the modulation of social behaviour in tilapia, but it was not possible to identify specific roles for specific AVT neuronal populations. The results presented here also contrast with those previously published for another cichlid species with a similar mating system, which highlights the species-specific nature of the pattern of association between AVT and social behaviour even within the same taxonomic family.


What criteria do patients use when judging the effectiveness of psoriasis management?
Judgements on the effectiveness of psoriasis management are based on clinical criteria employed by dermatologists, and how they take account of patients' experiences in the process of history taking. In this study the aim was to gain the in-depth patients' perspective and investigate the criteria that they employ when making judgements about the effectiveness of their therapy. These findings were then compared with the clinical and research literature on the clinical effectiveness of psoriasis treatments. The study design is exploratory-descriptive, using a qualitative ethnographic approach. In-depth interviews were undertaken in an outpatient department dermatology clinic. A purposive sample of 20 adult patients currently attending represented the following types of psoriasis: guttate, chronic plaque and scalp. A key comparable finding between the literature and the interview data is that dermatologists emphasize observable criteria of effectiveness, such as clearance of the lesion, whereas patients emphasis focuses on the subjective concerns, such as suppleness, softness and alleviation of itch. This discrepancy needs to be considered during history taking, in relation to its impact on therapy concordance and in the use and development of outcome measures used for clinical assessment and evaluations of psoriasis therapy.


Tetrahydrogestrinone is a potent but unselective binding steroid and affects glucocorticoid signalling in the liver.
Tetrahydrogestrinone (THG) is a steroid recently identified to be misused as doping agent. However, the knowledge on functions of this substance in humans or animal models is rather limited. Therefore, it was our aim to further characterize the pharmacological profile of THG and identify potential adverse side effects. THG was synthesized, the purity was confirmed and its biological activity was tested. The potency of THG to transactivate AR dependent reporter gene expression was two orders of magnitude lower compared to dihydrotestosterone. THG binds with high affinity but unselective to the androgen (AR), progesterone (PR), glucocorticoid (GR) and mineralocorticoid (MR) receptor. Treatment of orchiectomised rats with THG resulted in a stimulation of prostate, seminal vesicle and levator ani muscle, indicating androgenic and anabolic properties. In the liver THG, in contrast to testosteronepropionate (TP), down regulates the expression of the GR dependent tyrosine aminotransferase gene (TAT). In summary, our results demonstrate that THG is not a specific AR agonist. THG exhibits a high binding affinity to all tested steroid hormone receptors and binds with highest affinity to the GR. Our in vivo data are indicative of an anabolic and androgenic potency of THG, but the repression of TAT demonstrates that THG also interferes with the glucocorticoid hormone system. Therefore, it is conceivable that an intake will result in adverse side effects.


Polyphenols and Their Nanoformulations: Protective Effects against Human Diseases.
Polyphenols are the secondary metabolites synthesized by the plants as a part of defense machinery. Owing to their antioxidant, anti-inflammatory, anticancerous, antineoplastic, and immunomodulatory effects, natural polyphenols have been used for a long time to prevent and treat a variety of diseases. As a result, these phytochemicals may be able to act as therapeutic agents in treating cancer and cardiovascular and neurological disorders. The limited bioavailability of polyphenolic molecules is one issue with their utilization. For the purpose of increasing the bioavailability of these chemicals, many formulation forms have been developed, with nanonization standing out among them. The present review outlines the biological potential of nanoformulated plant polyphenolic compounds. It also summarizes the employability of various polyphenols as nanoformulations for cancer and neurological and cardiovascular disease treatment. Nanoencapsulated polyphenols, singular or in combinations, effective both in vitro and in vivo, need more investigation.


Orally administered δ opioid agonist peptide rubiscolin-6 stimulates food intake in aged mice with ghrelin resistance.
It is known that a decline in food intake occurs with aging. In this study, we investigated changes in parameters associated with food intake in response to aging, and whether orexigenic peptides stimulated food intake after peripheral administration even in aged mice. Food intake and body weight of 27-month-old male C57BL/6N mice were lower than those of 15-month-old mice. Epididymal and mesenteric fat mass, blood glucose, triglyceride, and leptin levels were also decreased. Meanwhile, the hypothalamic mRNA expression of endogenous orexigenic peptides such as neuropeptide Y (NPY) and agouti-related protein, also called agouti-related peptide, was increased. Next, we tested responsiveness to exogenously administered orexigenic peptides coupled to NPY in aged as well as young mice. Orally administered rubiscolin-6, a δ opioid agonist hexapeptide derived from a major green leaf protein Rubisco, stimulated food intake in 27-month-old mice. In contrast, ghrelin was ineffective after intraperitoneal administration to aged mice, suggesting that the NPY system downstream of ghrelin but not δ opioid receptors might be impaired in aged mice. Orally administered rubiscolin-6 stimulates food intake in aged mice with ghrelin resistance.


Influence of lifelong cumulative HIV viremia on long-term recovery of CD4+ cell count and CD4+/CD8+ ratio among patients on combination antiretroviral therapy.
We explored the impact of lifelong cumulative HIV viremia on immunological recovery during antiretroviral therapy, according to the timing of treatment initiation. We estimated lifelong cumulative HIV viremia in patients followed in the ANRS PRIMO cohort since primary infection, including 244 patients who started treatment during PHI and had at least one treatment interruption, and 218 patients who started treatment later but with no interruptions. The impact of cumulative viremia on current immunological status was analysed using linear and logistic regression models. At the last visit on treatment, median CD4 cell count was 645 cells/μl in the early/intermittent treatment group (median time from infection 9.5 years, 4.8 years of continuous treatment since last resumption), and 654 cells/μl in the deferred/continuous treatment group (median time from infection 6.1 years, 3.0 years of continuous treatment). Only 36.1 and 39.8% of patients achieved a CD4/CD8 ratio of more than 1, respectively. Current CD4 cell count was not associated with cumulative HIV viremia in either group. In contrast, patients with high cumulative HIV viremia (>66th percentile vs. <33rd percentile) were less likely to achieve a CD4/CD8 ratio of more than 1 (26.8 vs. 43.3%, P = 0.003), even after controlling for the baseline CD4/CD8 ratio, treatment duration, sex and age. Much higher CD4 cell count and CD4/CD8 ratio were reached in early/continuous treatment, that is low viremia exposure group. Our results underline the critical need in early-treated patients to maintain adherence, in order to limit cumulative HIV viremia and optimize immunological recovery, notably the CD4/CD8 ratio.


[Quantitative determination of elements in plant samples by laser ablation inductively coupled plasma mass spectrometry].
The 193 nm excimer laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was used for the quantification of 13 elements (Li, B, Na, Mg, Al, K, Ca, Cr, Mn, Fe, Ni, Cu and Ba) in the plant samples (GBW070602, GBW070605 and GBW08514). Indium standard solution with known concentration was mixed into samples and used as an internal standard. Afterwards the samples were ground again and pressed to disks. NIST SRM 610 glass material reference standard was used as the external standard in the LA-ICP-MS measurements. In contrast to longer wavelength ablation techniques, in this experiment a round crater with low deposits could be achieved during ablation. And another study was done on the effect of homogenization over the powder disk It was clearly shown that the analytical results under the condition of 193 nm LA-ICP-MS, using NIST SRM 610 as the external standard for analysis of pressed disk of plant sample, are in good agreement with certified values.


Temporoporal metabolic abnormalities in temporal lobe epilepsies.
Positron emission tomography (PET) may be used to map regional cerebral glucose metabolism using 18F-deoxyglucose-PET in patients with partial epilepsy. An area of reduced glucose metabolism, that is commonly more extensive than the underlying anatomical abnormality, is reported in most of the patients with medically refractory partial epilepsy. These functional changes are useful in the delineation of the epileptogenic focus prior to surgery. Nevertheless, in patients with mesial temporal lobe epilepsy (MTLE) without mass lesion, the hypometabolism involves a large area of the temporal lobe, including the mesial structures, the temporal pole and part of the lateral temporal cortex. In such patients with MTLE, subcortical structures and extratemporal lobe areas are also often hypometabolic. The reasons for this large hypometabolism remain debated. In MTLE patients, the most severe hypometabolism is found in the temporo-polar region. The clinical significance of this temporo-polar hypometabolism is unknown. The pathophysiology of interictal hypometabolism probably involves several mechanisms, such as neuronal loss, deafferentation, postictal depression, and others epilepsy-related phenomena. The relationship between interictal temporo-polar hypometabolism and seizure onset or seizure spread remain speculative.


Stability, electronic and magnetic properties of embedded triangular graphene nanoflakes.
Stability, electronic and magnetic properties of triangular graphene nanoflakes embedded in graphane (graphane-embedded TGNFs) are investigated by density functional theory. It is found that the interface between the embedded TGNF and graphane is stable since the diffusion of H atoms from the graphane region to the embedded TGNF is energetically unfavorable with high energy barriers. The electronic and magnetic properties of the system completely depend on the embedded TGNF. The band gaps of graphane-embedded ATGNFs (armchair-edged TGNFs) arise due to the quantum confinement, while the special characteristics of nonbonding states of graphane-embedded ZTGNFs (zigzag-edged TGNFs) play an important role in their electronic properties. As the edge sizes increase, the differences of band gaps between graphane-embedded TGNFs and the isolated ones decrease. Furthermore, owing to the partially paired p(z) orbitals of edge C atoms, graphane-embedded ZTGNFs exhibit a ferrimagnetic ground state with size-dependant total spin being consistent with Lieb's theorem. Our work provides a possible way to obtain TGNFs without physical cutting.


Improvement of pain therapy in laboratory mice.
Pain of minor grades is difficult to detect in laboratory mice, because mice hide signs of injury and suffering. Low-grade post-operative pain was detected by continuous measurements of heart beat rate and variability, as well as nesting behaviours. Pain relief regimens with non-steroidal anti inflammatory drugs were shown to be effective.


Effects of two oral contraceptives, containing 30 or 20 microg of ethinyl estradiol in combination with gestodene, on blood coagulation and fibrinolysis in Brazilian women.
Blood coagulation and fibrinolytic variables were evaluated in 46 Brazilian women treated with either of two monophasic oral contraceptives (OC), containing 30 or 20 microg of ethinyl estradiol, and 75 microg of gestodene. The effects on procoagulants, anticoagulants, pro-fibrinolytics and antifibrinolytics and fibrin turnover were evaluated after treatment for six consecutive cycles, the impact of reduction of ethinyl estradiol dosage on these effects being assessed. The OC containing 30 microg of ethinyl estradiol significantly increased the activities of factors VIII and X, whereas the one containing 20 microg of ethinyl estradiol caused no changes in clotting factors. Neither treatment altered fibrinogen levels or factor VII, IX or XII activity. There were no changes in antithrombin levels, but treatment with 30 microg ethinyl estradiol increased protein C levels and treatment with 20 microg decreased total protein S levels. Concerning the fibrinolytic parameters, both OCs increased plasminogen activity, whereas no changes in PAI-1, t-PA, alpha-2-antiplasmin or fibrin degradation products were observed. The reduction in ethinyl estradiol dosage from 30 microg to 20 microg eliminated the effects on factors VIII and X. The results show that the OC studied did not cause sufficient changes to indicate that there may be a correlation between these laboratory alterations and clinical results. The lack of reports concerning the hemostatic effects of OCs on Brazilian women hinders comparison of the present data with those obtained for other ethnic groups, at different geographical locations, and emphasizes the importance of such a study for future epidemiological investigation of the prothrombotic effects of OCs in Brazilian women.


[Sanitary and epidemiological supply for the Russian Army during the First World War (1914-1918)].
At the beginning of the First World War the most typical diseases in the Russian Army were typhoid, typhus, diphtheria, cholera, smallpox and other infectious diseases. At the beginning of the First World War the level of infectious morbidity was significantly low, but further increased and pandemic risk arose. Servicemen were mostly ill with typhus, relapsing fever, flux, cholera, smallpox and typhoid. The highest mortality rate was registered in patients with cholera, typhus and typhoid. According the prewar deployment program of the Russian Army anti-epidemiologic facilities were established. By the end of war were established 110 sanitary-and-hygienic and 90 disinfection units. However, organization of anti-epidemiologic security was unsatisfactory. Due to lack of specialists and equipment anti-epidemiologic facilities of units were under strength. Commanders of sanitary units and sanitary service had not enough resources for operational service in the Forces and facilities of rear area.


A case of Pneumocystis jiroveci pneumonia in X-linked agammaglobulinaemia treated with immunosuppressive therapy: a lesson for immunologists.
The case of a 20-year-old patient, affected by X-linked agammaglobulinaemia (XLA), who developed severe pneumonia from Pneumocystis jiroveci (formerly Pneumocystis carinii) (PCP), is reported. This infection usually affects patients with AIDS, children affected by severe combined immunodeficiency or hypogammaglobulinaemia with hyperimmunoglobulin M, or patients undergoing severe immunosuppression. The XLA patient developed PCP during therapy with steroids and cyclosporine A, carried out for several months, due to an extended skin vasculitis, accompanied by general symptoms. The pneumonia had a severe clinical course, requiring a long hospitalization. At the diagnosis of PCP, immunosuppressive therapy was suspended and the patient recovered after a long-term trimethoprim/sulfamethoxazole therapy. Immunological studies revealed an unexpected normal number of CD4+ and CD8+ T cells. The two subsets had an exclusive naïve phenotype (95% CD4+CD45RA+CD62L+ and 89% CD8+CD45RA+CD62L+ cells), with an absence of primed cells. Lymphoproliferative responses to P. carinii and recall antigens as well as to mitogens were extremely deficient. During the follow-up, memory cells appeared with recovery of the lymphoproliferative response to mitogens and maintained defective responses to antigens. This is one of the few reported XLA cases experiencing severe PCP. In this patient, the infection became clinically evident during immunosuppressive therapy. We believe that the absence of functional activities, despite a normal level of T lymphocyte counts, sustained this long-lasting infection. Thus, the CD4+ and CD8+ T cell count evaluation, without functional studies, may not be per se sufficient for predicting the risk of a severe clinical course of PCP in patients undergoing immunosuppression.


Ginsenoside-Rd Promotes Neurite Outgrowth of PC12 Cells through MAPK/ERK- and PI3K/AKT-Dependent Pathways.
Panax ginseng is a famous herbal medicine widely used in Asia. Ginsenosides have been identified as the principle active ingredients for Panax ginseng's biological activity, among which ginsenoside Rd (Rd) attracts extensive attention for its obvious neuroprotective activities. Here we investigated the effect of Rd on neurite outgrowth, a crucial process associated with neuronal repair. PC12 cells, which respond to nerve growth factor (NGF) and serve as a model for neuronal cells, were treated with different concentrations of Rd, and then their neurite outgrowth was evaluated. Our results showed that 10 μM Rd significantly increased the percentages of long neurite- and branching neurite-bearing cells, compared with respective controls. The length of the longest neurites and the total length of neurites in Rd-treated PC12 cells were much longer than that of respective controls. We also showed that Rd activated ERK1/2 and AKT but not PKC signalings, and inhibition of ERK1/2 by PD98059 or/and AKT by LY294002 effectively attenuated Rd-induced neurite outgrowth. Moreover, Rd upregulated the expression of GAP-43, a neuron-specific protein involved in neurite outgrowth, while PD98059 or/and LY294002 decreased Rd-induced increased GAP-43 expression. Taken together, our results provided the first evidence that Rd may promote the neurite outgrowth of PC12 cells by upregulating GAP-43 expression via ERK- and ARK-dependent signaling pathways.


[Care-Related intervention in Rehabilitative Pneumology: Pulmonary Rehabilitation in Chronic Obstructive Broncopneumopathies (COPD) can benefit from a multidisciplinary approach?]
Chronic Obstructive Pulmonary Disease (COPD) is a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation. Cardiovascular diseases, osteoporosis, depression/anxiety, musculoskeletal impairment and obstructive sleep apnea are frequent and important comorbidities in COPD, often under-diagnosed, and associated with poor health status and prognosis. Pulmonary rehabilitation improves symptoms, quality of life, pulmonary function, and health care in patients with chronic respiratory disease. By definition it is a comprehensive intervention based on a thorough patient assessment followed by patient-tailored therapies that include, but are not limited to, exercise training, education, and behavior change and designed to improve the physical and psychological condition of people with chronic respiratory disease and to promote the long-term adherence to health-enhancing behaviors. Exercise limitation in patients with COPD is multifactorial and includes ventilatory limitation, gas transfer abnormalities, pulmonary vascular and cardiac dysfunction, limb muscle dysfunction, and comorbid impairments. Overall, pulmonary rehabilitation aims to improve cardiorespiratory and skeletal muscle function improving respiratory symptoms and quality of life in daily life activities adding a synergic support to the pharmacologic inhaled therapy. COPD has a variable natural history, but most of the time chronic respiratory failure complicates disease progression. Supplemental oxygen and noninvasive mechanical ventilation have been proven to improve survival and reduce hospital admissions in COPD patients. Furthermore additional studies have shown that exercise performance benefit from supplemental oxygen and NIV used both during rehabilitation exercise programs and over the night. In conclusion, an overarching approach to diagnosis, assessment of severity of COPD and its frequent comorbidities should guide to a multidisciplinary and synergic approach in terms of pharmacological and nonpharmacological management of a systemic inflammatory syndrome.


Evaluating clinical information systems.
As members of organizational committees to evaluate and select clinical information systems, nurse executives must identify a system that not only has the core functionality to support necessary changes in workflow and optimize nurse productivity and patient safety but that also is embraced by the nursing staff. There are specific features that nurse executives must demand to help nurses at the bedside reap the greatest benefit from the technology.


Tissue localization of the copper chaperone ATOX1 and its potential role in disease.
ATOX1 is a cytoplasmic copper chaperone that interacts with the copper-binding domain of the membrane copper transporters ATP7A and ATP7B. ATOX1 has also been suggested to have a potential anti-oxidant activity. This study investigates the tissue-specific localization of the mouse homolog, Atox1, in mouse liver and kidney. Immunohistochemical studies in the liver localize the copper chaperone to hepatocytes surrounding both hepatic and central veins. In the kidney, Atox1 is localized to the cortex and the medulla. Cortex immunostaining is specific to glomeruli in both the juxtamedullary and cortical nephrons. Expression in the medulla appears to be associated with the loops of Henle. These data suggest that localized regions in the liver and kidney express Atox1 and have a role in copper homeostasis and/or anti-oxidant protection. Twenty-seven patients with Wilson disease-like phenotypes and two patients with Menkes disease-like phenotypes were screened for ATOX1 mutations with no alterations detected. The human phenotype resulting from mutations in ATOX1 remains unidentified.


Pseudomonas aeruginosa: Evaluation of Pathogen Burden and Drug-Resistance Trends in a Tertiary Care Hospital.
To evaluate the pathogen burden and antibiotic-resistance trends of Pseudomonas aeruginosa among hospitalised patients at a tertiary care hospital. Retrospective, hospital record-based, cross-sectional study. Microbiology Laboratory, Allama Iqbal Medical College/Jinnah Hospital, Lahore, from January 2014 to December 2016. A total of 5,960 samples were collected from clinically suspected cases of bacterial infections, admitted to the hospital. Microbial identification and antibiotic susceptibility pattern were carried out and analysed. Out of a total of 5,960 samples, Pseudomonas aeruginosa was isolated from 1,268 (21.2%) specimens. Department-wise isolation rate was n=600 (42.9%), n=268 (15.4%), n=201 (12.6%), and n=199 (16.0%) from intensive care unit (ICU), surgical units, medical units, and Gynae wards, respectively (p<0.0001). Sample-wise isolation rate was, wound swabs n=448 (35%), urine n=356 (28%), sputum n=187 (14 %), tracheal aspirate n=127 (10%), blood n=99 (7%), and broncho-alveolar lavage n=51 (4%) (p<0.0001). Drug-resistance pattern showed low rates for carbapenems(meropenem n=440 (35%), Imipenem n=436 (34%) and beta-lactam + beta-lactamase inhibitor combination (piperacillin+tazobactam n=437 (34%) while alarming rates were observed for cephalosporins (ceftazidime n=716 (56%), fluoroquinolones (ciprofloxacin n=690 (54%), cefoperazone+sulbactam n=685 (54%), aminoglycosides (gentamicin, n=669 (53%), amikacin n=608 (48%), and monobactams (aztreonam n=666 (52%). Decreasing trend was observed only for amikacin 63% to 37%, aztreonam showed similar pattern throughout, while there was an increasing trend of drug resistance in all groups of antibiotics. Emerging drug-resistant strains of Pseudomonas aeruginosa are probably linked to the injudicious use of antibiotics, leading to ineffective empirical therapy. Therefore, we suggest that culture and antimicrobial susceptibility testing should be done for targeted antimicrobial therapy against Pseudomonas aeruginosa.


Comparison of topical 0.3% ofloxacin with fortified tobramycin plus cefazolin in the treatment of bacterial keratitis.
Ofloxacin is a broad spectrum fluoroquinolone antibiotic with good ocular penetration. We compared ofloxacin 3% solution with a combination of fortified tobramycin sulphate and cefazolin sodium solutions in the treatment of culture-proven bacterial keratitis. Thirty eyes with culture-proven bacterial corneal ulcers were enrolled in a prospective randomised, controlled, double-masked study for comparison. The ofloxacin drop and saline were decanted into two identical-looking bottles to the tobramycin and cefazolin. The cases were randomly allocated into treatment with 0.3% ofloxacin solution or a combination of fortified antibiotics (1.5% tobramycin and 10% cefazolin solutions; control group) along with supportive cycloplegic, vitamins and anti-glaucoma therapy. Student's t-test was used to compare the results. Staphylococcus aureus and coagulase-negative staphylococci were the two most common organisms isolated. Resolution of the ulcer was achieved in 93% and 87% of cases in the ofloxacin and control groups respectively. The mean time required for symptomatic relief was 7.8 +/- 1.54 days and for epithelial healing 15.0 +/- 3.86 days in ofloxacin group, compared with 8.33 +/- 1.54 days for symptomatic relief and 15.46 +/- 3.86 days for epithelial healing in the control group. Post-resolution best corrected visual acuity of 20/200 or better was achieved in all but one eye in both groups. Ofloxacin and combined fortified tobramycin and cefazolin topical drops were comparable for treating cases of bacterial corneal ulcer. However, considering its easy availability and cost-effectiveness, monotherapy with ofloxacin is preferred over the combined fortified tobramycin and cefazolin therapy.


Efficiency of infiltration with bupivacain after modified radical mastectomy.
Pre-incisional infiltration of anaesthetic is proven to reduce postoperative pain in breast cancer surgery. However, studies of post-incisional infiltration for modified radical mastectomy are rare. The purpose of this study was to investigate whether post-incisional infiltration with bupivacaine provides improved postoperative pain relief and a cost-effective benefit. This is a retrospective study. Between January 2006 and May 2008, 139 patients who received modified radical mastectomy were recruited to participate in the study. Patients receiving local infiltration received bupivacaine (0.5% bupivacaine, 5 ml diluted to 10 ml with distilled water) injected into the dermis surrounding the incision after wound suture. Pain intensity was evaluated using a Visual Analogue Scale (VAS) score and measurement of the required doses of meperidine and acetaminophen. The pain score was recorded every eight hours for three days. All patients were female. Seventy-two patients received local infiltration with bupivacaine after wound suture and 67 patients did not. There were no significant differences between the two patient groups in age, body weight and height, length of general anaesthesia and operative time. Hospital stay was significantly shorter for patients receiving local infiltration of bupivacaine. The VAS score was higher up to 16 hours post-surgery for patients who did not receive local infiltration. Meperidine and acetaminophen consumption was less for patients who received local infiltration (P = 0.010). Post-incisional wound infiltration with bupivacaine can relieve pain during the first 16 hours after surgery and shorten hospital stay, and it provides a cost-effective benefit.


A novel rat model of blast-induced traumatic brain injury simulating different damage degree: implications for morphological, neurological, and biomarker changes.
In current military conflicts and civilian terrorism, blast-induced traumatic brain injury (bTBI) is the primary cause of neurotrauma. However, the effects and mechanisms of bTBI are poorly understood. Although previous researchers have made significant contributions to establishing animal models for the simulation of bTBI, the precision and controllability of blast-induced injury in animal models must be improved. Therefore, we established a novel rat model to simulate blast-wave injury to the brain. To simulate different extents of bTBI injury, the animals were divided into moderate and severe injury groups. The miniature spherical explosives (pentaerythritol tetranitrate) used in each group were of different sizes (2.5 mm diameter in the moderate injury group and 3.0 mm diameter in the severe injury group). A specially designed apparatus was able to precisely adjust the positions of the miniature explosives and create eight rats with bTBI simultaneously, using a single electric detonator. Neurological functions, gross pathologies, histopathological changes and the expression levels of various biomarkers were examined after the explosion. Compared with the moderate injury group, there were significantly more neurological dysfunctions, cortical contusions, intraparenchymal hemorrhages, cortical expression of S-100β, myelin basic protein, neuron-specific enolase, IL-8, IL-10, inducible nitric oxide synthase, and HIF-1α in the severe injury group. These results demonstrate that we have created a reliable and reproducible bTBI model in rats. This model will be helpful for studying the mechanisms of bTBI and developing strategies for clinical bTBI treatment.


An adaptive and generalizable closed-loop system for control of medically induced coma and other states of anesthesia.
Design of closed-loop anesthetic delivery (CLAD) systems is an important topic, particularly for medically induced coma, which needs to be maintained for long periods. Current CLADs for medically induced coma require a separate offline experiment for model parameter estimation, which causes interruption in treatment and is difficult to perform. Also, CLADs may exhibit bias due to inherent time-variation and non-stationarity, and may have large infusion rate variations at steady state. Finally, current CLADs lack theoretical performance guarantees. We develop the first adaptive CLAD for medically induced coma, which addresses these limitations. Further, we extend our adaptive system to be generalizable to other states of anesthesia. We designed general parametric pharmacodynamic, pharmacokinetic and neural observation models with associated guidelines, and derived a novel adaptive controller. We further penalized large steady-state drug infusion rate variations in the controller. We derived theoretical guarantees that the adaptive system has zero steady-state bias. Using simulations that resembled real time-varying and noisy environments, we tested the closed-loop system for control of two different anesthetic states, burst suppression in medically induced coma and unconsciousness in general anesthesia. In 1200 simulations, the adaptive system achieved precise control of both anesthetic states despite non-stationarity, time-variation, noise, and no initial parameter knowledge. In both cases, the adaptive system performed close to a baseline system that knew the parameters exactly. In contrast, a non-adaptive system resulted in large steady-state bias and error. The adaptive system also resulted in significantly smaller steady-state infusion rate variations compared to prior systems. These results have significant implications for clinically viable CLAD design for a wide range of anesthetic states, with potential cost-saving and therapeutic benefits.


Screening of candidate gene responses to cadmium stress by RNA sequencing in oilseed rape (Brassica napus L.).
Cadmium (Cd) stress is one of the most serious threats to agriculture in the world. Oilseed rape (Brassica napus L.) is an important oil crop; however, Cd can easily accumulate in rapeseed and thus harm human health through the food chain. In the first experiment, our purpose was to measure the Cd accumulation in mature B. napus plants and its influences on fatty acid composition. The results showed that most Cd was accumulated in the root, and the seed fatty acid content was considerably different at different Cd toxicity levels. In the second experiment, 7-day-old B. napus seedlings stressed by Cd (1 mM) for 0 h (CK-0h), 24 h (T-24h), or 72 h (T-72h) were submitted to physiological and biological analyses, RNA-Seq and qRT-PCR. In total, 5469 and 6769 differentially expressed genes (DEGs) were identified in the comparisons of "CK-0h vs T-24h" and "CK-0h vs T-72h", respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that the photosynthetic and glutathione (GSH) pathways were significantly enriched in response to Cd stress. Key factors in the response to Cd stress included BnPCS1, BnGSTU12, BnGSTU5, and BnHMAs. The transcription factors BnWRKY11 (BnaA03g51590D), BnWRKY28 (BnaA03g43640D), BnWRKY33 (BnaA03g17820D), and BnWRKY75 (BnaA03g04160D) were upregulated after Cd exposure. The present study revealed that upregulation of the genes encoding GST and PCS under Cd stress promoted the formation of low-molecular weight complexes (PC-Cd), and upregulation of heavy metal ATPase genes induced PC-Cd transfer to vacuoles. These findings may provide the basis for the molecular mechanism of the response of B. napus to Cd.


Implementation of a Stress Intervention with Latino Immigrants in a Non-traditional Migration City.
Stress negatively impacts health outcomes across all racial and ethnic groups, but the health disparities experienced by Latino immigrants in nontraditional migration cities are exacerbated by undeveloped infrastructure and weak social support networks. Immigrants in new migration cities can be difficult to engage in health interventions and are therefore underrepresented in the very research where their inclusion is most crucial. To effectively engage Latino immigrants, a team of academic and community researchers collaborated on a community-based participatory research project to design and implement a stress and coping intervention. Top stressors reported were family, children, and work, but health was most commonly identified as the primary stressor. Participants overwhelmingly chose physical activity goals for stress reduction. Pre- to post- intervention results revealed significant improvements in social support and stress management. Results demonstrate the effectiveness of a peer-led, community-partnered approach to implementing a stress intervention with Latino immigrants in a nontraditional migration city.


Synthesis and biological properties of 7alpha-cyano derivatives of the (17alpha,20E/Z)-[125I]iodovinyl- and 16alpha-[125I]iodo-estradiols.
The synthesis, receptor binding affinity, estrogenic potency and tissue distribution of the 7alpha-cyano derivatives of the (17alpha,20E/Z)-[125I]iodovinyl-(CIVE) and 16alpha-[125I]iodo-estradiols (CIE) are reported. The iodovinyl derivatives were prepared via the (17alpha,20E/Z)-tri-n-butylstannyl intermediates, derived from the addition of tri-n-butyl tin hydride to the 17alpha-ethynyl group of the 7alpha-cyano-17alpha-ethynylestradiol, using triethylborane as a catalyst. The no-carrier-added [125I]-CIVE isomers were prepared via the same stereospecific reaction. [125I]-CIE was prepared from 7alpha-cyano-16beta-bromoestradiol via halogen exchange with Na125I. Addition of the 7alpha-cyano group to 16alpha-iodoestradiol did not affect estrogen receptor binding affinity (RBA of CIE is 115). However the estrogenic potential of CIE, as measured by the capacity to stimulate the expression of the pS2 gene, was reduced to 1% as compared to that of estradiol. Addition of a 7alpha-cyano group to the (17alpha,20E/Z)-IVE isomers reduced the RBA to 21 and 36, respectively, while the estrogenic potential was reduced to 2-3% of that of estradiol. Uterus uptake in immature rats of the 125I-labeled CIVE 20E-isomer and the 16alpha-iodo CIE peaked at 0.5h post injection while the (17alpha,20Z)-CIVE isomer showed a maximum only past 5h post injection. Uptake of all three 125I-labeled 7alpha-cyanoestrogens was suppressed by the co-injection of non-radioactive estradiol confirming the role of estrogen receptors in the localization process. Uterus retention pattern differ substantially from those of the analogues 7alpha-methylestrogens, which were previously shown to give high maximum 125I-uptake values at 2h post injection. Overall our data indicate that addition of a 7alpha-cyano group to 123I-labeled estrogens does not improve their potential to serve as SPECT agents for the imaging of estrogen receptor densities in breast cancer.


The Expressions of TGF-β(1) and IL-10 in Cultured Fibroblasts after ALA-IPL Photodynamic Treatment.
Topical photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) was originally used for treating superficial skin tumors. The application of PDT to other inflammatory dermatoses like acne vulgaris, psoriasis, granuloma annulare, localized scleroderma and lichen sclerosus has recently been introduced. However, the underlying mechanisms are not well understood. We've previously reported the induction of tumor growth factor (TGF)-β(1) and interleukin (IL)-10 after PDT with ALA and intense pulsed light (IPL) in cultured HaCaT cells. The purpose of this study was to investigate the expressions of TGF-β(1) and IL-10 in cultured fibroblasts after PDT with using ALA and IPL. Cultured fibroblasts were treated with ALA-IPL PDT (1µmol/L of ALA; 0, 4, 8 and 12 J/cm(2) of IPL). The expressions of TGF-β(1) and IL-10 were investigated by reverse transcription-polymerase chain reaction and enzyme linked immunosorbent assay. TGF-β(1) mRNA and protein were reduced down to 0.52- and 0.63-fold, respectively, after PDT and the IL-10 protein was increased up to 2.74-fold after PDT. The reduction of TGF-β(1) was prominent after PDT and so an antisclerotic effect can be expected after PDT. The induction of IL-10 may contribute to the anti-inflammatory effect, which explains the therapeutic benefit of PDT for inflammatory dermatoses.


The pathology of Marburg virus disease.
A description of the postmortem pathological findings in a case of Marburg virus disease emphasizes the findings of focal necrosis in the liver, spleen and lymphoid tissue, disseminated intravascular coagulation and acute tubular necrosis. These features are compared and contrasted with those of other potentially fatal viral haemorrhagic fevers to help pathologists make an early diagnosis wherever possible.


Clinical and biochemical predictors of very preterm birth in twin-to-twin transfusion syndrome treated by fetoscopy.
To evaluate pre- and postoperative predictors of preterm birth in twin-to-twin transfusion syndrome treated with fetoscopic placental laser coagulation. Prospective cohort study (n = 166) assessing cervical length (pre and postoperatively), amniotic fluid interleukin-6, serum C-reactive protein and duration of surgery. Logistic regression was used to investigate associations with preterm delivery. Preterm delivery within 7 days, before 28.0 and 32.0 weeks occurred in 4.8%, 16.8%, and 28.9%, respectively. The only significant predictor of delivery within 7 days was postoperative cervical length (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.3-0.9). Concerning delivery before 32.0 weeks, preoperative cervical length (OR, 0.9; 95% CI, 0.8-1.0), and gestational age (OR, 0.8; 95% CI, 0.4-0.9) were independent risk factors but the association was weak. The presence of a single survivor after surgery was associated with a clear reduction of risk (OR, 0.3; 95% CI, 0.1-0.6). Inflammatory biomarkers and duration of surgery did not discriminate risk of prematurity. No strong preoperative predictive factor of preterm birth could be identified. A single survivor was a strong protective factor of very preterm birth.


Impact of Obesity on the Course of Management of Inflammatory Bowel Disease-A Review.
It is already well-known that visceral adipose tissue is inseparably related to the pathogenesis, activity, and general outcome of inflammatory bowel disease (IBD). We are getting closer and closer to the molecular background of this loop, finding certain relationships between activated mesenteric tissue and inflammation within the lumen of the gastrointestinal tract. Recently, relatively new data have been uncovered, indicating a direct impact of body fat on the pattern of pharmacological treatment in the course of IBD. On the other hand, ileal and colonic types of Crohn's disease and ulcerative colitis appear to be more diversified than it was thought in the past. However, the question arises whether at this stage we are able to translate this knowledge into the practical management of IBD patients or we are still exploring the scientific background of this pathology, having no specific tools to be used directly in patients. Our review explores IBD in the context of obesity and associated disorders, focusing on adipokines, creeping fat, and possible relationships between these disorders and the treatment of IBD patients.


Analysis of Risk Factors for Coronary Artery Lesion in Children with Kawasaki Disease.
To determine the frequency of coronary artery lesion (CAL) in children with Kawasaki disease (KD) and to analyse the related risk factors of CAL and the predictive value of risk factors for CAL. A descriptive study. Department of Pediatrics, People's Hospital of Linquan County, Anhui Province, China, from January 2019 to January 2022. Clinical data of 71 children with KD were retrospectively analysed, including 31 in the CAL group and 40 in the non-CAL group. The age, gender, days of fever, blood routine, plasma N-terminal B-type natriuretic peptide (NT-proBNP), and Kobayashi score were registered as independent variables of all the children, and the presence or absence of CAL was used as the dependent variable. All the independent variables were subjected to univariate analysis between the groups, and those with significance in univariate analysis were further subjected to unconditional binary logistic regression analysis. A receiver operating curve (ROC) was drawn to analyse the predictive power and optimal cut-off value of related risk factors for CAL. On univariate analysis, age, NT-proBNP and Kobayashi's score were closely related to CAL (all p<0.05). Multivariate analysis showed that NT-proBNP and Kobayashi scores were independent risk factors for CAL in children with KD. ROC curve analysis showed that the area under the curve (AUC) of NT-proBNP and Kobayashi scores were 0.771 and 0.732, respectively, at optimal critical values of 543.12 ng/L and 7.50 points, respectively. The frequency of CAL in children with KD is high. NT-proBNP and Kobayashi scores are independent risk factors for the occurrence of CAL in children with KD, and they have good predictive performance for the diagnosis of CAL. Kawasaki disease, Children, Coronary artery lesion, Risk factors, Kobayashi score, NT-pro BNP.


Effect of Sarcosine (a Glycine Transport 1 Inhibitor) and Risperidone (an Atypical antipsychotic Drug) on MK-801 Induced Learning and Memory Deficits in Rats.
The present study was carried out to evaluate whether the combined administration of sarcosine with risperidone possess any advantageous effects on dopaminergic and NMDA receptor-mediated glutamatergic neurotransmissions as compared to single drug administration in rats. The Wistar rats were divided into 7 groups each with different treatments. MK-801 (0.1 mg/kg, i.p.) was injected as single dose on 14th day for inducing learning and memory deficits in animals. Sarcosine (300 and 600 mg/kg, i.p.) and risperidone (0.2 mg/kg, i.p.) were administered daily for 14 days. Spatial habituation learning and hole board tests were performed on 14th day followed by measurement of GABA and 5-HT levels in brain tissues of rats. Pretreatment of sarcosine (600 mg/kg, i.p.) non-significantly improved learning and memory deficits induced by non-competitive NMDA receptor antagonist MK-801, significantly increased the GABA and decreased the 5-HT levels (p<0.05). Combined administration of sarcosine (300 mg/kg, i.p.) with risperidone (0.1 mg/kg, i.p.) synergistically improved cognitive deficits significantly, decreased % errors in hole board learning test, and increased centre time, corner time in spatial habituation learning test (p<0.05). The combined administration also potentiated the GABA and decreased 5-HT levels, indicating that the increased synaptic glycine concentrations may enhance NMDA receptor function which is directly linked with increased GABAergic transmission in striatum region and decreased 5-HT levels showed antagonistic action hence, enhancing the cognition. Our results suggest that combined administration of sarcosine with risperidone may strengthen glutamatergic tone in striatum. Thus, it may be a novel regime to improve psychotic symptoms and cognitive deficit in schizophrenia.


The Root Extract of Peucedanum praeruptorum Dunn Exerts Anticancer Effects in Human Non-Small-Cell Lung Cancer Cells with Different EGFR Mutation Statuses by Suppressing MET Activity.
The aim of this study was to investigate the anticancer effects of the root extract of Peucedanum praeruptorum Dunn (EPP) in human non-small-cell lung cancer (NSCLC) cells and explore the mechanisms of action. We used four types of human lung cancer cell lines, including H1299 (epidermal growth factor receptor (EGFR) wild-type), PC9 (EGFR Glu746-Ala750 deletion mutation in exon 19; EGFR tyrosine kinase inhibitor (TKI)-sensitive), H1975 (EGFR L858R/T790M double-mutant; EGFR TKI-resistant), and PC9/ER (erlotinib-resistant) cells. EPP suppressed cell growth and the colony formation of NSCLC cells in a concentration-dependent manner. EPP stimulated chromatin condensation, increased the percentage of sub-G1 phase cells, and enhanced the proportion of annexin V-positive cells, demonstrating that EPP triggered apoptosis in NSCLC cells regardless of the EGFR mutation and EGFR TKI resistance status. The phosphorylation level of the signal transducer and activator of transcription 3 (STAT3) and AKT was decreased by EPP. The expression of STAT3 target genes was also downregulated by EPP. EPP reversed hepatocyte growth factor (HGF)-induced MET phosphorylation and gefitinib resistance. Taken together, our results demonstrate that EPP exerted anticancer effects not only in EGFR TKI-sensitive NSCLC cells, but also in EGFR TKI-resistant NSCLC cells, by suppressing MET activity.


Simultaneous modelling of the thermal degradation kinetics of pectin methylesterase in lettuce (Lactuca sativa L.) and carrot (Daucus carota L.) extracts: analysis of seasonal variation and tissue type.
The thermal degradation kinetics of pectin methylesterase (PME) from carrot and lettuce were studied. Fresh extracts were exposed to temperatures from 55 to 70 degrees C until the enzyme was inactivated. A model based on the presence of two forms of the enzyme, one active and one non-active, is proposed. The natural variability of the PME activity was taken into the model in the form of normally distributed random effects. The common model parameters obtained (cleavage constant (0.0395+/-0.0062 s(-1)), degradation constant (0.556+/-0.112 s(-1)), cleavage energy of activation (469+/-23 kJ mol(-1)) and degradation energy of activation (488+/-18 kJ mol(-1))) show that the PME degradation kinetics of the two vegetables can be explained with a single set of parameters.


Quercetin protects against high glucose-induced damage in bone marrow-derived endothelial progenitor cells.
Endothelial progenitor cells (EPCs), a group of bone marrow-derived pro-angiogenic cells, contribute to vascular repair after damage. EPC dysfunction exists in diabetes and results in poor wound healing in diabetic patients with trauma or surgery. The aim of the present study was to determine the effect of quercetin, a natural flavonoid on high glucose‑induced damage in EPCs. Treatment with high glucose (40 mM) decreased cell viability and migration, and increased oxidant stress, as was evidenced by the elevated levels of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase in bone marrow-derived EPCs. Moreover, high glucose reduced the levels of endothelial nitric oxide synthase (eNOS) phosphorylation, nitric oxide (NO) production and intracellular cyclic guanosine monophosphate (cGMP). Quercetin supplement protected against high glucose‑induced impairment in cell viability, migration, oxidant stress, eNOS phosphorylation, NO production and cGMP levels. Quercetin also increased Sirt1 expression in EPCs. Inhibition of Sirt1 by a chemical antagonist sirtinol abolished the protective effect of quercetin on eNOS phosphorylation, NO production and cGMP levels following high glucose stress. To the best of our knowledge, the results provide the first evidence that quercetin protects against high glucose‑induced damage by inducing Sirt1-dependent eNOS upregulation in EPCs, and suggest that quercetin is a promising therapeutic agent for diabetic patients undergoing surgery or other invasive procedures.


X-ray photoelectron spectroscopy study of thin TiO2 films cosputtered with Al.
In this study, titanium dioxide (TiO(2)) films were fabricated by cosputtering of a titanium (Ti) target and an aluminum (Al) slice in a smaller area by an ion-beam sputtering deposition method. The sputtered films were postannealed at 450 degrees C. The x-ray photoelectron spectroscopy spectra were categorized by their oxygen bonding variations, which include high-binding-energy oxygen, (HBO), bridging oxygen, low-binding-energy oxygen, and shifts of the binding energies (BEs) of oxygen (O) and Ti signals. The enhancement of HBO and higher BE shifts of the O 1s spectra as a function of cosputtered Al in the film imply the formation of an Al-O-Ti linkage. Corresponding changes in the Ti 2p spectra further confirm the modification of properties of the cosputtered film that results from the variation of the chemical bonding environment. An observed correlation between the chemical structure and optical absorption of the Al cosputtered films can be used to modify the optical properties of the film.


Prenatal diagnosis of fetal gastroschisis using three-dimensional ultrasound: comparison between the 20th and 21st centuries.
In order to compare the trends and improvements of prenatal diagnosis of gastroschisis, we herein retrospectively reviewed our cases of fetal gastroschisis detected by three-dimensional ultrasound (3D US) between the two centuries. We reviewed our computer database of prenatal diagnosis on gastroschisis in National Cheng Kung University Hospital from October 1994 to November 2011. All the fetuses were initially scanned by two-dimensional (2D) US to locate the region of interest (ROI). Then, the 3D probe was used to scan all the ROI systematically and mechanically, and all the images were stored on laser discs for further 3D visualization and reconstruction. To compare the characteristics at prenatal diagnosis of gastroschisis between the 20th and 21st centuries in our hospital, the Chi-square test and Student t test were used. The p values less than 0.05 and 0.1 were considered statistically significant. In total, 26 fetuses with gastroschisis were depicted by 3D US in utero (10 cases were diagnosed in the 20th century and 16 cases in the 21st century). The ranges of gestational age at prenatal diagnosis of gastroschisis by 3D US in the 20th century were between 14 and 34 weeks (mean: 21.6 weeks) and between 14 and 33 weeks (mean: 21.9 weeks) in the 21st century. Moreover, seven cases (70%) were diagnosed before the third trimester in the 20th century, whereas 13 cases (81%) were diagnosed before the third trimester in the 21st century. Although without statistical significance, higher prenatal diagnosis rate before the third trimester in the 21st century was noted. The improvement of 3D US has remarkable advantages in adding novel visual depiction of a 3D lesion of a 3D fetus in 3D US after reconstruction and thus assists substantially in prenatal diagnosis, genetic consultation, and perinatal management of gastroschisis.


Skeletal muscle sodium glucose co-transporters in older adults with type 2 diabetes undergoing resistance training.
We examined the expression of the sodium-dependent glucose co-transporter system (hSGLT3) in skeletal muscle of Hispanic older adults with type 2 diabetes. Subjects (65+/-8 yr) were randomized to resistance training (3x/wk, n=13) or standard of care (controls, n=5) for 16 weeks. Skeletal muscle hSGLT3 and GLUT4 mRNA transcript levels were determined by real time RT-PCR. hSGLT3 transcripts increased by a factor of ten following resistance training compared to control subjects (0.10, P=0.03). There were no differences in GLUT4 mRNA expression levels between groups. Protein expression levels of these transporters were confirmed by immunohistochemistry and Western blotting. hSGLT3 after resistance exercise was found not to be co-localized with the nicotinic acetylcholine receptor. The change in hSGLT3 transcript levels in the vastus lateralis muscle was positively correlated with glucose uptake, as measured by the change in muscle glycogen stores (r=0.53, P=0.02); and with exercise intensity, as measured by the change in muscle strength (r=0.73, P=0.001). Group assignment was be the only independent predictor of hSGLT3 transcript levels, explaining 68% of its variability (P=0.01). Our data show that hSGLT3, but not GLTU4, expression was enhanced in skeletal muscle after 16 weeks of resistance training. This finding suggests that hSGLT3, an insulin-independent glucose transporter, is activated with exercise and it may play a significant role in glycemic control with muscle contraction. The hSGLT3 exact mechanism is not well understood and requires further investigation. However its functional significance regarding a reduction of glucose toxicity and improvement of insulin resistance is the subject of ongoing research.


Corruption kills: estimating the global impact of corruption on children deaths.
Information on the global risk factors of children mortality is crucial to guide global efforts to improve survival. Corruption has been previously shown to significantly impact on child mortality. However no recent quantification of its current impact is available. The impact of corruption was assessed through crude Pearson's correlation, univariate and multivariate linear models coupling national under-five mortality rates in 2008 to the national "perceived level of corruption" (CPI) and a large set of adjustment variables measured during the same period. The final multivariable model (adjusted R(2)= 0.89) included the following significant variables: percentage of people with improved sanitation (p.value<0.001), logarithm of total health expenditure (p.value = 0.006), Corruption Perception Index (p.value<0.001), presence of an arid climate on the national territory (p = 0.006), and the dependency ratio (p.value<0.001). A decrease in CPI of one point (i.e. a more important perceived corruption) was associated with an increase in the log of national under-five mortality rate of 0.0644. According to this result, it could be roughly hypothesized that more than 140000 annual children deaths could be indirectly attributed to corruption. Global response to children mortality must involve a necessary increase in funds available to develop water and sanitation access and purchase new methods for prevention, management, and treatment of major diseases drawing the global pattern of children deaths. However without paying regard to the anti-corruption mechanisms needed to ensure their proper use, it will also provide further opportunity for corruption. Policies and interventions supported by governments and donors must integrate initiatives that recognise how they are inter-related.


Pretreatment with recombinant human TSH changes the regional distribution of radioiodine on thyroid scintigrams of nodular goiters.
In a recent study, we demonstrated that pretreatment with a single, low dose of recombinant human TSH (rhTSH) doubles 24-h thyroid radioactive iodine uptake in patients with nodular goiter. The purpose of the present study was to investigate whether rhTSH pretreatment induces changes in the regional distribution of radioiodine as visualized on thyroid scintigrams in these patients. Anterior planar thyroid 123I scintigrams were obtained in 26 patients with a nodular goiter (23 women and 3 men; age, 62 +/- 9 yr, mean +/- SD; thyroid weight, 165 +/- 72 g) 24 h after administration of a diagnostic dose of radioiodine. All patients were studied twice: first, without rhTSH pretreatment (baseline study), and second, after an im injection of 0.01 mg (n = 10) or 0.03 mg rhTSH (n = 16), given 24 h before radioiodine administration (rhTSH study). For quantification of regional differences in radioiodine uptake, a region of interest method was used. Upon visual inspection, baseline scintigrams showed a heterogeneous uptake of radioiodine. In general, rhTSH scintigrams also showed heterogeneous radioiodine uptake. In some patients, the distribution of radioiodine in the rhTSH scintigram was considerably more homogeneous than in the baseline scintigram. In a few patients, originally "cold" areas had changed into "hot" ones, whereas originally hot areas had changed into cold ones. Quantification of regional radioiodine uptake showed that pretreatment with rhTSH caused a larger increase in radioiodine uptake in relatively cold areas and a smaller increase in radioiodine uptake in relatively hot areas, compared with the increase in radioiodine uptake in the entire thyroid. In patients with a baseline serum TSH level of 0.5 mU/liter or lower, the increase in radioiodine uptake in relatively cold areas was significantly larger than in patients with a baseline serum TSH level higher than 0.5 mU/liter. In conclusion, a single, low dose of rhTSH not only doubled 24-h radioactive iodine uptake but also caused a more homogeneous distribution of radioiodine within the thyroid gland in patients with a nodular goiter by stimulating radioiodine uptake in relatively cold areas more than in relatively hot areas. This was most marked in patients with a low baseline serum TSH level. Our data suggest that pretreatment with rhTSH may improve the efficacy of radioiodine treatment for volume reduction of nodular goiters, especially in patients with a low baseline serum TSH level.


[Antibodies against galectin-8 in patients with systemic lupus erythematosus].
The family of lectins known as galectins (galectins 1-14) are involved in the regulation of the immune system and in oncogenesis. During a search for antigens recognized by antibodies produced by a patient with systemic lupus erythematosus (SLE) we found reactivity against galectin-8, for which autoantibodies have not been previously described. To determine the frequency of autoantibodies against galectin-8 in lupus patients compared with healthy controls. Galectin-8 was purified from a bacterial expression system and used in immunoblot assays as antigen to screen the sera of 55 SLE patients and matched controls. Disease activity was evaluated using the Mexican Modification of the Systemic Lupus Erythematosus Disease Activity Index (MEX-SLEDAI). Reactivity against galectin-8 was detected in 30% of SLE patients, compared to 7% of controls (p=0.003). We could not detect any particular SLE manifestation associated to the presence of these autoantibodies. This is the first description of autoantibodies against galectin-8. Its higher frequency in patients with SLE suggests a pathogenic role. Further studies are needed to determine their clinical relevance.


Influencing Factors of Depression among Adolescent Asians in North America: A Systematic Review.
Asian American adolescents experience rates of depression comparable to or greater than those of other ethnic minorities. The purpose of this systematic review is to summarize psychosocial factors related to depressive symptoms of Asian American adolescents between the ages of 10 to 19. Various electronic databases were systematically searched to identify research articles published from 2000 to 2021, and the psychosocial factors influencing depression among Asian adolescents in North America were examined. A total of 81 studies were included in this systematic review. Consistent findings on relationships between depressive symptoms and influencing factors included (a) acculturative stress, (b) religious or spiritual significance for females, (c) parent-child cohesion, (d) harsh parenting style, (e) responsive parenting style, (f) racial or ethnic discrimination, (g) being bullied, (h) positive mentor presence, and (i) exposure to community violence. Collectively, the majority of included studies suggest that depressive symptoms were more likely found among Asian American adolescents who (a) are older, (b) are female, (c) have immigrant status, (d) exhibit coping behaviours, (e) face academic challenges, (f) face a poor socioeconomic situation, (g) perceive parent-child conflict, (h) perceive maternal disconnectedness, and (i) perceive negative peer relations. A number of conflictive findings also existed. This systematic review provides a summary of the various psychosocial factors on individual, familial, and social levels, which influenced the depressive symptoms of Asian American adolescents. Such findings offer a starting point to examine what factors should be necessarily included in related depression-preventive intervention design and evaluation. Culturally sensitive care, strengthened family-school-community collaboration, and targeted research efforts are needed to meet the needs of Asian adolescents experiencing a range of depressive symptoms.


Tutorial on use of intraclass correlation coefficients for assessing intertest reliability and its application in functional near-infrared spectroscopy-based brain imaging.
Test-retest reliability of neuroimaging measurements is an important concern in the investigation of cognitive functions in the human brain. To date, intraclass correlation coefficients (ICCs), originally used in interrater reliability studies in behavioral sciences, have become commonly used metrics in reliability studies on neuroimaging and functional near-infrared spectroscopy (fNIRS). However, as there are six popular forms of ICC, the adequateness of the comprehensive understanding of ICCs will affect how one may appropriately select, use, and interpret ICCs toward a reliability study. We first offer a brief review and tutorial on the statistical rationale of ICCs, including their underlying analysis of variance models and technical definitions, in the context of assessment on intertest reliability. Second, we provide general guidelines on the selection and interpretation of ICCs. Third, we illustrate the proposed approach by using an actual research study to assess interest reliability of fNIRS-based, volumetric diffuse optical tomography of brain activities stimulated by a risk decision-making protocol. Last, special issues that may arise in reliability assessment using ICCs are discussed and solutions are suggested.


Stories of childhood sexual abuse (CSA) among older adults living with HIV (OALH) in South Carolina: a qualitative study.
ABSTRACTChildhood sexual abuse (CSA) devastatingly impacts an individual's behavioral, psychological, and social health. Childhood, a developmental stage directly influenced by the home or school environment, leaves a life-long imprint. Compared with the general population, CSA prevalence is doubled among people living with HIV. Thus, the study aimed to explore CSA circumstances among older adults living with HIV (OALH) in South Carolina (SC). We included 24 OALH aged 50 and above who reported CSA. The data were collected at an immunology center in SC. In-depth semi-structured interviews were conducted, audio-recorded, transcribed, and analyzed using a thematic analysis approach. The iterative analytic process included a discussion of initial thoughts and key concepts, identification, and reconciliation of codes, and naming of emergent themes. Six themes emerged: known perpetrators, re-victimization, "nobody believed me", "cannot live like others", lack of CSA disclosure, and interconnections with other adverse childhood experiences (ACEs). CSA experiences and non-disclosure were found to be linked with shame, embarrassment, fear, and trust issues. Hence, trauma-focused interventions are required to resolve these issues and improve the quality of life of OALH with past trauma. Counseling or therapy programs should incorporate psychological and behavioral theoretical models to best target OALH who are CSA survivors.


Tomato phytochemicals and prostate cancer risk.
Mounting evidence over the past decade suggests that the consumption of fresh and processed tomato products is associated with reduced risk of prostate cancer. The emerging hypothesis is that lycopene, the primary red carotenoid in tomatoes, may be the principle phytochemical responsible for this reduction in risk. A number of potential mechanisms by which lycopene may act have emerged, including serving as an important in vivo antioxidant, enhancing cell-to-cell communication via increasing gap junctions between cells, and modulating cell-cycle progression. Although the effect of lycopene is biologically relevant, the tomato is also an excellent source of nutrients, including folate, vitamin C, and various other carotenoids and phytochemicals, such as polyphenols, which also may be associated with lower cancer risk. Tomatoes also contain significant quantities of potassium, as well as some vitamin A and vitamin E. Our laboratory has been interested in identifying specific components or combination of components in tomatoes that are responsible for reducing prostate cancer risk. We carried out cell culture trials to evaluate the effects of tomato carotenoids and tomato polyphenols on growth of prostate cancer cells. We also evaluated the ability of freeze-dried whole-tomato powder or lycopene alone to reduce growth of prostate tumors in rats. This paper reviews the epidemiological evidence, evaluating the relationship between prostate cancer risk and tomato consumption, and presents experimental data from this and other laboratories that support the hypothesis that whole tomato and its phytochemical components reduce the risk of prostate cancer.


Outbreak of beri-beri in a prison in West Africa.
The International Committee of the Red Cross investigated an outbreak of beri-beri in a prison in West Africa. Twenty-five prisoners out of a total of 1020 died over a period of 11 weeks--exceeding the crude mortality rate of 1/10,000/day, a threshold for serious concern. Two hundred and eleven prisoners had clinical signs of beri-beri. An immediate response to treatment with thiamine was seen and no further deaths occurred. The triad of a positive squatting test, oedema and a diet consisting exclusively of white rice should lead to the diagnosis of beri-beri. The disease is more common than generally assumed, also in Africa and especially in prisons.


Modification of pulmonary oxygen toxicity by bleomycin treatment.
The purpose of this study was to determine whether pretreatment of rabbits with bleomycin would modify their response to 100% O2 and, if so, to identify the mechanism of this action. A single intratracheal injection of bleomycin (5 U/kg) resulted in a transient decrease of the arterial Po2, its mean value (+/- SE) 7 days postinjection being 59 +/- 3 Torr. All animals were either killed or exposed to 100% O2 35 days postinjection. At this time, arterial Po2 had returned to its control level. On the other hand, lung hydroxyproline content had doubled and static compliance and the total lung capacity had decreased by 22 and 31%, respectively, indicating the existence of significant lung fibrosis. Furthermore, activities of catalase and superoxide dismutase in lung homogenates were higher than control and were further augmented by exposure to 100% O2 for 64 h. These biochemical changes may account, at least in part, for the mitigation of the toxic effects of hyperoxia, as shown by the delayed appearance of arterial hypoxemia, and the 50% increase in survival time when bleomycin injected rabbits were exposed to 100% O2 35 days postinjection.


Appropriate experimental approaches for predicting abuse potential and addictive qualities in preclinical drug discovery.
Drug abuse is an increasing social and public health issue, putting the onus on drug developers and regulatory agencies to ensure that the abuse potential of novel drugs is adequately assessed prior to product launch. This review summarizes the core preclinical data that frequently contribute to building an understanding of abuse potential for a new molecular entity, in addition to highlighting models that can provide increased resolution regarding the level of risk. Second, an important distinction between abuse potential and addiction potential is drawn, with comments on how preclinical models can inform on each. While the currently adopted preclinical models possess strong predictive validity, there are areas for future refinement and research. These areas include a more refined use of self-administration models to assess relative reinforcement; and the need for open innovation in pursuing improvements. There is also the need for careful scientifically driven application of models rather than a standardization of methodologies, and the need to explore the opportunities that may exist for enhancing the value of physical dependence and withdrawal studies by focusing on withdrawal-induced drug seeking, rather than broad symptomology.


Designing heart performance by gene transfer.
The birth of molecular cardiology can be traced to the development and implementation of high-fidelity genetic approaches for manipulating the heart. Recombinant viral vector-based technology offers a highly effective approach to genetically engineer cardiac muscle in vitro and in vivo. This review highlights discoveries made in cardiac muscle physiology through the use of targeted viral-mediated genetic modification. Here the history of cardiac gene transfer technology and the strengths and limitations of viral and nonviral vectors for gene delivery are reviewed. A comprehensive account is given of the application of gene transfer technology for studying key cardiac muscle targets including Ca(2+) handling, the sarcomere, the cytoskeleton, and signaling molecules and their posttranslational modifications. The primary objective of this review is to provide a thorough analysis of gene transfer studies for understanding cardiac physiology in health and disease. By comparing results obtained from gene transfer with those obtained from transgenesis and biophysical and biochemical methodologies, this review provides a global view of cardiac structure-function with an eye towards future areas of research. The data presented here serve as a basis for discovery of new therapeutic targets for remediation of acquired and inherited cardiac diseases.


Cell budding from pre-invasive tumors: Intrinsic precursor of invasive breast lesions?
Our previous studies showed that in patients with ductal carcinoma in situ (DCIS) of the breast, the tumor cells that overlie focal myoepithelial cell layer disruptions (FMCLDs) are generally arranged as finger-like projections that bud into the stroma. These budding cells have significantly more genetic instability and invasion-related gene expression, and less estrogen receptor (ER) expression, than their epithelial cell counterparts. This study aimed to assess these cells for potential molecular markers that are uniquely associated with cell adhesion and motility. Seventeen ER-positive DCIS cases were screened by immunostaining for ER, and 7 cases which harbored FMCLD lesions were used to examine the expression of the potential markers. Two cases with both DCIS and invasive lesions were selected for comparing the differences in molecular expression between these lesion types. The results showed that expression levels of talin, E-cadherin and focal adhesion kinase (FAK) in tumor cells overlying FMCLDs were higher than those within the corresponding duct. Integrin β1 staining was detected only in a small number of the tumor cells overlying the FMCLDs. Vinculin staining was weak (18%) or not detected (82%), and no expression was found in the tumor cells within the corresponding duct or in the pure isolated DCIS. By contrast, the expression levels of talin, vinculin and integrin β1 in the invasive tumors were distinctly higher than those in DCIS, and the expression of FAK and E-cadherin was lower. Using electron microscopy, we found that the tight junctions between tumor cells overlying the FMCLDs were reduced compared to the adjacent tumor cells in the lumen. These results indicate that the tumor cells overlying FMCLDs are likely to represent the specific precursors of invasive breast lesions. Our findings may also facilitate the identification of specific targets for further molecular profiling, which will more completely characterize this important cell population.


Who declines from antenatal serum alpha-fetoprotein screening--and why?
One hundred women who declined a voluntary alpha-fetoprotein screening test during early pregnancy and one hundred women who accepted the test were investigated by means of semistructured interviews with particular reference to background factors which could have influenced upon the decision making. Those who declined were, as expected, overrepresented among those opposed to legal abortion and they often showed an ambivalent or negative attitude towards prenatal diagnosis as such. These women were also more frequently legally married and active members of various religious denominations. Otherwise there were no socioeconomic, psychologic or other background factors specially associated with women who declined. The paramount individual reason given for abstaining from the test was the feeling that the test was 'unreliable'. The personal ethical attitude, together with the current reputation of the test in society, seem to be major factors affecting the rate of participation in an AFP-screening program.


[Loosening of a Calcaneo-Stop Screw after Trampolining].
Flexible flatfoot is a common malalignment in the paediatric population. Arthroereisis with a calcaneo-stop screw is an effective surgical procedure for treating juvenile flexible flatfoot after conservative measures have been fully exploited. In the present report, we describe the case of a loosening of a calcaneo-stop screw in a 12-year-old youth after excessive trampolining.


Forazoline A: marine-derived polyketide with antifungal in vivo efficacy.
Forazoline A, a novel antifungal polyketide with in vivo efficacy against Candida albicans, was discovered using LCMS-based metabolomics to investigate marine-invertebrate-associated bacteria. Forazoline A had a highly unusual and unprecedented skeleton. Acquisition of (13)C-(13)C gCOSY and (13)C-(15)N HMQC NMR data provided the direct carbon-carbon and carbon-nitrogen connectivity, respectively. This approach represents the first example of determining direct (13)C-(15)N connectivity for a natural product. Using yeast chemical genomics, we propose that forazoline A operated through a new mechanism of action with a phenotypic outcome of disrupting membrane integrity.


Unclassified mycobacteria isolated from human suspect tuberculosis cases in New-foundland: preliminary studies on fifteen strains.
Unclassified mycobacteria were isolated from 36 of 35,555 clinical specimens cultured for M. tuberculosis. The majority of isolations were from patients suspected of having tuberculosis and from whom repeat attempts at culture failed to yield typical tubercle bacilli. Fifteen strains thus far studied were not capable of causing generalized tuberculosis in guinea pigs, and all were highly resistant to the commonly employed antituberculous therapeutic agents. Eleven of the 15 strains were resistant to 100 or more mug./ml. of streptomycin; 12 strains were resistant to 25 or more mug./ml. of para - aminosalicylic acid; and all 15 showed growth in the presence of 50 or more mug./ml. of isoniazid. All strains were niacin-negative and catalase-positive. In the absence of other cultural findings, isolation of anonymous mycobacteria poses a major problem, especially in those cases in which the clinical and radiographic findings are typically those of tuberculosis.