Superwarfarin and glass ingestion with prolonged coagulopathy requiring high-dose vitamin K1 therapy.
A 23-year-old man was brought to the emergency department after eating four boxes of brodifacoum-containing rodenticide over a 4-day interval and pieces from approximately two bottles of glass over the previous 2 weeks. He was asymptomatic but his prothrombin time was markedly elevated with an international normalized ratio (INR) of 37.8. A plain abdominal film showed diffuse radiopaque foreign bodies, presumably glass, in the large and distal small intestines. Treatment for ingested glass consisted of stool softeners and bulk-forming laxatives. The patient developed mild gingival bleeding and received fresh frozen plasma (FFP) infusions and vitamin K1 orally. At a vitamin K1 dosage of 300 mg/day, the INR corrected to less than 2.0 and the patient was discharged taking that dosage. He returned 26 days later with hematuria and flank pain, and his INR was 189. He was administered FFP and packed red blood cells, and his vitamin K1 dosage was increased to 800 mg/day; his INR returned to baseline. Compliance with taking the vitamin K1, which required ingestion of 60-160 tablets/day, was a serious problem, requiring numerous follow-up calls and visits to the patient at home and work. At 5-month follow he was doing well. Compliance with large daily doses of vitamin K1 for treatment of "superwarfarin" ingestion may be poor because of the duration of treatment and large number of pills required. A more concentrated formulation may be advantageous for management of patients with brodifacoum poisoning.


Generation and Research of Online English Course Learning Evaluation Model Based on Genetic Algorithm Improved Neural Set Network.
The rationality and timeliness of the comprehensive results of English course learning quality are increasingly important in the process of modern education. There are some problems in the scientific evaluation of English course learning quality and teachers' own English course learning, such as the need for proper adjustment and improvement. Based on the improved network theory of genetic algorithm, this paper takes an online English course learning quality evaluation model and uses MATLAB 7.0 to write the graphical user interface of the neural set network English course learning quality prediction model. The model uses the genetic algorithm of adaptive mutation to optimize the initial weights and values of the neural set network and solves the problems of prediction accuracy and convergence speed of English course learning quality evaluation results. Simulation experiments show that the neural set network has a strong dependence on the initial weights and thresholds. Using the improved genetic algorithm to optimize the initial weights and thresholds of the neural set network reduced the time for the neural set network to find the weights and thresholds that meet the training termination conditions, the prediction accuracy was increased to 0.897, the prediction accuracy was 78.85%, and the level prediction accuracy was 84.62%, which effectively promoted the development of online English course learning in colleges and the continuous improvement of teachers' English course learning level.


Association of free testosterone and sex hormone binding globulin with metabolic syndrome and subclinical atherosclerosis but not blood pressure in hypertensive perimenopausal women.
Data on the role of androgens as potential mediators of increasing cardiovascular risk in women at midlife are controversial. The aim of the study was to analyze the relationship of free testosterone (FT) and sex hormone binding globulin (SHBG) with blood pressure and subclinical organ damage and metabolic syndrome (MS) in middle aged hypertensive women. One hundred and fifty-two women with newly diagnosed arterial hypertension were included in the study. In all subjects blood pressure measurements were performed as well as echocardiographic examination with left ventricular structure and function assessment (GE Vivid 7.0), carotid ultrasound with measurement of intima-media thickness (IMT), and carotid-femoral pulse wave velocity (PWV) measurement (Sphygmocor). A fasting blood sample was taken to measure glucose and lipid concentrations. Serum testosterone and SHBG were measured. Free testosterone was calculated according to the Vermeulen formula. Metabolic syndrome was defined following the International Diabetes Federation (IDF) recommendations. Free testosterone was significantly higher and SHBG lower in women with MS independently of menopausal status. The odds ratio of MS per quartile increment in FT after adjustment for covariates was 2.06 (95% CI: 1.16-3.65). There was no correlation between FT, SHBG and blood pressure. Free testosterone was associated with decreased left ventricular diastolic function (E/A ratio β = -0.19, p = 0.05) and subclinical atherosclerosis (IMT β = 0.34, p = 0.009), but not arterial stiffness. Free testosterone and SHBG independently of menopause status are related to MS. Free testosterone is associated with worse metabolic profile, subclinical atherosclerosis and impaired diastolic function of the left ventricle.


The valsalva maneuver revisited: the influence of voluntary breathing on isometric muscle strength.
We assessed the effects of 4 voluntary breathing conditions on maximal voluntary isometric force of large muscle groups. Ten subjects performed maximum voluntary isometric contractions (MVICs) of knee flexion and extension, shoulder abduction and adduction, and elbow flexion and extension under all breathing conditions: normal breathing, forced inhalation, forced exhalation, and the Valsalva maneuver (VM). Forced exhalation significantly increased peak force during shoulder adduction, elbow extension, and knee extension MVIC tasks (p = 0.001, 0.024, and 0.002, respectively); the peak force during the Valsalva maneuver was not different from forced exhalation for all tested muscle groups. No voluntary breathing condition seemed to influence the peak force during the knee flexion, elbow flexion, and shoulder abduction MVIC tasks. The results demonstrate that voluntary breathing imposes a significant impact on isometric muscle strength. Given the increased cardiovascular risks associated with the Valsalva maneuver, it is highly recommended that forced exhalation be used during exercise at maximal levels, especially in repetitive repetitions.


Role of ginsenoside Rd in inhibiting 26S proteasome activity.
Drugs targeting 26S proteasome as antitumor agents are considered to be important for cancer therapy. Although the active components are yet to be identified, for more than 1000 years, the low-toxicity Panax ginseng has been used in traditional herbal medicine for either treating or preventing cancer. Ginsenosides Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1 are distinct components that can be isolated from P. ginseng C.A. Meyer. In this study 26S proteasome was purified from pig red blood cells, and the activity of the seven isolated ginsenosides was analyzed by proteolysis assay. It was found that ginsenoside Rd inhibited 52.9% the chymotrypsin-like activity of 26S proteasome with an IC(50) value of 107.5 microM when Suc-LLVY-AMC was used as a substrate. Ginsenoside Rd displayed a mixed type inhibition of 26S proteasome when analyzed by Lineweaver-Burk plots of the inhibition kinetics. Unlike ginsenoside Rd, the other ginsenosides showed low inhibitory effect of the chymotrypsin-like activity of 26S proteasome. Seven ginsenosides did not inhibit the trypsin-like and caspase-like activities of 26S when Ac-RLR-AMC or Z-LLE-AMC was used as substrate. These results suggest that ginsenoside Rd is a potential drug for cancer prevention due to its specific 26S proteasome inhibitory effect and known low toxicity. Furthermore, both 3-O-Glc(2)-Glc and 20-O-beta-Glc positions of the ginsenoside may play a role in the inhibitory property of the chymotrypsin-like activity in 26S proteasome.


Dynamic control of mode modulation and spatial multiplexing using hybrid metasurfaces.
Designing reconfigurable metasurfaces that can dynamically control scattered electromagnetic waves and work in the near-infrared (NIR) and optical regimes remains a challenging task, which is hindered by the static material property and fixed structures. Phase change materials (PCMs) can provide high contrast optical refractive indexes at high frequencies between amorphous and crystal states, therefore are promising as feasible materials for reconfigurable metasurfaces. Here, we propose a hybrid metasurface that can arbitrarily modulate the complex amplitude of incident light with uniform amplitude and full 2π phase coverage by utilizing composite concentric rings (CCRs) with different ratios of gold and PCMs. Our designed metasurface possesses a bi-functionality that is capable of splitting beams or generating vortex beams by thermal switching between metal and semiconductor states of vanadium oxide (VO2), respectively. It can be easily integrated into low loss photonic circuits with an ultra-small footprint. Our metadevice serves as a novel paradigm for active control of beams, which may open new opportunities for signal processing, memory storage, holography, and anti-counterfeiting.


Dendrimer-based BH3 conjugate that targets human carcinoma cells.
Our previous studies have demonstrated the efficacy of generation 5 poly(amidoamine) dendrimers (G5-PAMAM) as a platform for the targeted delivery of chemotherapeutics. However, anticancer therapy can be subverted by anti-apoptotic changes in cancer cells. Bcl-2 and several of its peptides are commonly overexpressed in a number of cancers. A means to reverse this anti-apoptotic mechanism is to expose the cells to BH3 peptide, which has a homology to the anti-apoptotic Bcl-2 protein. This cannot be done indiscriminately because it can induce apoptosis in normal cells. In order to specifically target BH3 peptides to cancer cells, we synthesized a trifunctional, G5-PAMAM-based nanodevice to which folic acid was conjugated as a targeting agent, along with fluorescein isothiocyanate as the reporter agent and BH3 peptides that were used to induce apoptosis. The results show, for the first time, the therapeutic potential of targeted BH3 peptides as a means of inducing apoptosis by interfering with anti-apoptotic proteins within specific cells.


Improved HSV-1 amplicon packaging using virion host shutoff mutants lacking mRNAse activity.
Given their generous transgene capacity and inherent neurotropism, herpes simplex virus (HSV-1)-based viral vectors are promising tools for gene delivery to the central nervous system. Despite their widespread pre-clinical use, vector toxicity remains a concern with regard to the use of herpes vectors in humans. One potential source of toxicity stems from the tegument-associated virion host shutoff protein (vhs), which induces translational arrest in the host cell through non-specific mRNAse activity. In the current study we utilized a series of HSV-1 viruses containing a deletion in the U(L)41 open reading frame to investigate: (1) the requirement of intact vhs function in amplicon packaging and (2) whether vhs influences the post-transduction survival of dissociated cortical neurons. Our results demonstrate that while amplicon yield was reduced an order of magnitude, U(L)41 deletion was associated with reduced vector toxicity. Furthermore, partial reconstitution of vhs function using mRNAse-inactive point mutants improved amplicon titers without imparting the toxicity observed with wild-type controls. These findings offer a novel approach to improving the titer and toxicity profiles of HSV-based viral vectors.


Effect of magnesium ions on the structure of DNA thin films: an infrared spectroscopy study.
Utilizing Fourier transform infrared spectroscopy we have investigated the vibrational spectrum of thin dsDNA films in order to track the structural changes upon addition of magnesium ions. In the range of low magnesium concentration ([magnesium]/[phosphate] = [Mg]/[P] < 0.5), both the red shift and the intensity of asymmetric PO2 stretching band decrease, indicating an increase of magnesium-phosphate binding in the backbone region. Vibration characteristics of the A conformation of the dsDNA vanish, whereas those characterizing the B conformation become fully stabilized. In the crossover range with comparable Mg and intrinsic Na DNA ions ([Mg]/[P] ≈ 1) B conformation remains stable; vibrational spectra show moderate intensity changes and a prominent blue shift, indicating a reinforcement of the bonds and binding in both the phosphate and the base regions. The obtained results reflect the modified screening and local charge neutralization of the dsDNA backbone charge, thus consistently demonstrating that the added Mg ions interact with DNA via long-range electrostatic forces. At high Mg contents ([Mg]/[P] > 10), the vibrational spectra broaden and show a striking intensity rise, while the base stacking remains unaffected. We argue that at these extreme conditions, where a charge compensation by vicinal counterions reaches 92-94%, DNA may undergo a structural transition into a more compact form.


Salivary biomarker C-reactive protein levels in children with sleep problems and Class II malocclusion before and after twin-block therapy.
Disturbances in sleep affects the overall quality of a child's life, with several short- and long-lasting consequences. Hence, early diagnosis and monitoring is crucial in the management of sleep disorders in children. The aim of this study was to evaluate salivary C-reactive protein (CRP) levels in a group of children with Class II malocclusion and sleep problems before and after twin-block appliance therapy. The study was a prospective clinical study with a 9-month follow-up period. Eleven children aged 8-12 years with skeletal Class II malocclusion and at least one sleep disorder were enrolled in the study. All children were subjected to a recording of their sleep history and a clinical as well as radiographic examination. Pretreatment levels of salivary CRP were recorded. A twin-block appliance was custom made and delivered to every child. At the end of 9-month follow-up, all children were recalled for a re-evaluation of salivary biomarker levels. Pretreatment and posttreatment changes in biomarker levels were assessed statistically using the students paired t-test. Levels of salivary biomarker CRP were significantly decreased in children following myofunctional therapy using a twin-block appliance (P < 0.001). There was a considerable improvement in the clinical symptoms such as a decrease in snoring and noisy breathing in most children post-twin-block therapy. The measurement of salivary biomarker CRP could be used as an alternative and noninvasive method to evaluate prognosis of oral myofunctional therapy for children with sleep disordered breathing.


Exit interaction effect on nascent product state distribution of O(1D)+N2O-->NO+NO.
We have determined the rotational state distributions of NO(v'=0,1,2) products produced from the reaction O(1D)+N2O. This is the first full characterization of the product rotational distribution of this reaction. The main part of each rotational distribution (up to j' approximately 80) has rotational temperature approximately 20,000 K and all these distributions are quite near to those predicted by the phase space theory (PST). This observation and previously reported vibrational distribution indicate that the most part of the energy partitioning of the reaction products is at least apparently statistical although the intermediate of this reaction is not so stable as to ensure the long lifetime. On the other hand, the distributions in the high rotational levels (j'=80-100) are found to decrease more sharply as j' increases than the PST predictions. The origin of the observed decrease of the distribution is discussed with quasiclassical trajectory (QCT) calculations on a five-dimensional ab initio potential energy surface (PES). The observed near-statistical distribution and the sharp decrease in the high-j' levels are well reproduced by a "half-collision" QCT calculation, where statistical distribution at the reaction intermediate is assumed. This agreement shows the rotation-translation interaction in the exit region has an effect of yielding small high-j' populations. However, a little bias of the calculated distribution toward lower rotational excitation than the observed one indicates that the combination of the statistical intermediate and the exit interaction on the current PES does not completely describe the real system. It is suggested that the reaction intermediate is generated with the distribution which is close to statistical but a little biased toward yielding high-j' products, and that the interaction in the exit region of the PES results in the sharp decrease in the high-j' levels.


Hyperfine Structure of Rotation-Inversion Levels in the Excited nu2 State of Ammonia
Hyperfine structures of the rotation-inversion transitions with J = 3 <-- 2, s <-- a, and K = 0, 1, 2, and with J = 0 <-- 1, a <-- s, and K = 0 in the excited nu2 vibrational state have been resolved and measured by sub-Doppler saturation spectroscopy using the Cologne terahertz spectrometer with an accuracy of about 1 kHz. The line frequencies of the hyperfine structures of the rotation inversion transitions (at 466, 769, 742, and 763 GHz) have been simultaneously analyzed with the previously published J = 2 <-- 1, s <-- a, K = 1, nu2 transition in terms of effective nuclear quadrupole and spin-rotation parameters. The corresponding pure rotation-inversion frequencies, deperturbed from the hyperfine effects, have also been derived. Copyright 1998 Academic Press.


ZnO hierarchical nanostructures: simple solvothermal synthesis and growth mechanism.
Hierarchical nano/micro structures of ZnO have been fabricated by solvothermal approach on sol-gel derived ZnO thin films. Paintbrush like nano/micro rod assembly, double-sided brush and windmill type architectures of ZnO are obtained when the ZnO thin film coated substrates were treated solvothermally in water at pH 10. Aligned nanorods are obtained at pH approximately 13.5 in water. In ethylenediamine-water solvent divergent micro/nanorod assemblies such as hemispherical dandelion, rice plant type bush of ZnO are obtained. Increase in the percentage of ethyelendiamine resulted in the formation of smaller assemblies of relatively thin nanorods. Initial slow reaction caused by the slow increase of the temperature inside the reaction medium and the different growth kinetics of the ZnO crystals are supposed to be the reason behind the architectural assemblies of the ZnO crystals.


Localization of metallothionein-I and -II in hypertrophic astrocytes in brain lesions of dogs.
To study the neurophysiological functions of metallothioneins (MTs), localization of MT-I and -II was examined immunohistochemically in a variety of brain lesions in dogs, including infarct, laminar cortical necrosis, hemorrhage, invasive growth of tumour, inflammatory lesions in granulomatous meningoencephalitis and distemper encephalitis. MT-I and -II were demonstrated in both nucleus and cytoplasm of hypertrophic astrocytes in most brain lesions examined regardless of the type, size, localization and duration of the lesions. In addition, MT expression was stronger in a population of hypertrophic astrocytes localizing inside of the surviving brain tissue rather than those localizing at the boundary between the surviving brain tissue and necrotic area, where severe inflammatory changes were developing. These results suggest that MT-I and -II may play roles not only in protection of neurons from metals and free radicals ubiquitous in the inflammatory lesions but also in repair of injured neural tissues.


Use of an image intensifier to remove a challenging foreign body in a segmental bronchiole.
Aspiration of foreign bodies into the tracheobronchial tree is a common presentation in children, but less so in adults. Successful extraction depends on the type of foreign body aspirated, location of the foreign body in the tracheobronchial tree, the experience of the operator and the instrumentation available. We report on our management of a patient who presented with an aspirated foreign body.


Colon penetration by a femoral prosthesis: a case report.
We report of a 57-year-old female patient who underwent a hemipelvectomy with a hemipelvic replacement in 1992. In 2013 the implanted material had to be partially removed due to a periprothetic infection. At that time a palacos spacer was implanted which penetrated two years later into the colon cavity.


Interrelationship between venous and arterial thrombosis.
In the past, arterial and venous thrombosis have been accepted as two completely different diseases. Recently, the thesis of two separate pathogenetic mechanisms of venous and arterial thrombosis has been challenged by accumulation of evidence which suggest that patients with atherothrombosis are at increased risk for venous thrombosis. Pathophysiological studies indicated that etiopathogenetic mechanisms of both diseases are similar and that coagulation and platelet activation participate in both venous and arterial thrombogenesis. Inflammation most probably represents the basic etiopathogenetic mechanism of arterial as well as venous thromboembolic disease, being a common mechanism through which different risk factors trigger thrombus formation in both veins and arteries. Atherothrombosis is accepted as a chronic inflammatory disease and the association between circulating inflammatory markers and venous thromboembolism also indicates an involvement of the inflammatory process in venous thrombosis. During inflammation, there is an increase in the production of procoagulant factors, a down-regulation of the anticoagulant mechanisms and an inhibition of the endogenic fibrinolytic activity. In line with the arguments which support the link between arterial and venous thrombosis is also the recognition that different risk factors are common in both diseases, such as age, metabolic syndrome, hypercholesterolemia and thrombophilia. A relation was also found between subjects with preclinical or clinical atherosclerotic disease and venous thromboembolism. These findings indicate close interrelationship between arterial atherothrombotic and venous thromboembolic disease. It could mean that atherosclerosis may induce venous thrombosis or that these two diseases have common risk factors which promote the development of both diseases.


Periodontitis and edentulism as risk indicators for mortality: Results from a prospective cohort study with 20 years of follow-up.
To investigate the association between periodontitis and edentulism with cardiovascular disease (CVD) and all-cause mortality. Baseline data of 506 subjects including 256 angiographically verified coronary artery disease patients and 250 matched participants in cardiovascular health from the Kuopio Oral Health and Heart study were collected from 1995-1996. Mortality data were accrued until May 31, 2015, and related to baseline periodontal health and edentulism, assessed as exposure and collected by means of clinical and radiographic examination by a single examiner. Cox proportional hazards regression models were fit using covariates such as age, gender, smoking, BMI, and education. The final sample size for the periodontitis models ranged from 358 to 376, while the edentate models included 413 to 503 subjects for CVD and all-cause mortality, respectively with no missing values in the predictor, confounders, and outcome. The strongest association was found between edentulism and CVD and all-cause mortality (HR: 1.9 CVD , HR: 1.6all-cause ; p < .01). Edentulism considered as a poor oral health marker was associated strongly with CVD mortality while periodontitis was not.


Generation and trapping reaction of an efficient 1,2-dehydrocarborane precursor, phenyl[o-(trimethylsilyl)carboranyl]iodonium acetate.
An efficient 1,2-dehydrocarborane precursor, phenyl[o-(trimethylsilyl)carboranyl]iodonium acetate, was readily prepared by reaction of [o-(trimethylsilyl)carboranyl]lithium and IPh(OAc)2. The facile 2+4 cycloaddition of with dienes such as anthracene, naphthalene, norborna-2,5-diene and 2,5-dimethylfuran gave high yields of the 1,2-dehydrocarborane adducts in the presence of a desilylating agent. The reaction of with a cyclic alkene and strained cycloalkynes afforded the adducts formed by the ene reaction and the 2+2 cycloaddition reaction. The reaction of with a bicyclopalladacycle yielded the cyclization product. The structures of compounds and were determined by single-crystal X-ray crystallography.


Augmented reality in intracranial meningioma surgery: report of a case and systematic review.
Augmented reality (AR) is as a useful and reliable tool in cranial surgery. We report the case of a left fronto-temporal meningioma in contact with the left Sylvian bifurcation, managed surgically with the aid of AR. We complete the picture with a systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Preoperatively, a careful segmentation of the tumor and the neighboring vessels was performed using our AR navigation software. A left fronto-temporal craniotomy was performed. Using the augmented optics technology, AR images injected into the microscope binocular during the surgery, allowed easy identification of the MCA branches and bifurcation. A systematic review of the literature was performed according to the PRISMA-P guidelines. A Simpson I resection was obtained, with no new neurological deficit and an uneventful recovery after surgery. The literature review identified eight separate articles published between 1998-2019, totaling 20 meningiomas surgically managed with the use of AR. Different AR systems are described in neurosurgery, with their respective advantages and disadvantages. Augmented optics allow the surgeon to focus on the procedure. No systematic data on postoperative radiological and clinical outcome were reported. The use of AR in meningioma surgery might help surgeons when confronted to lesions surrounded by complex structures. However, little data is available so far to support its routine use.


Thyroid hormones, catecholamine and cortisol concentrations after upper abdominal surgery.
Serum and plasma concentrations of thyroid hormones, catecholamines and cortisol as well as oxygen consumption were measured simultaneously in twenty patients in connection with cholecystectomy. Arterial blood samples were taken before surgery and at 2, 24, 48, 72 and 96 h after skin incision. A marked and prolonged decrease in T3 and free T3 concentrations was seen. A minor decrease in T4 was also observed but free T4 remained unchanged. TSH concentration was increased 2 h after skin incision, but at no other occasion. A marked increase in adrenaline and noradrenaline concentrations was observed 2 h after the start of surgery. This increase lasted 24 h for noradrenaline. There was a marked and prolonged rise in plasma cortisol after surgery. The oxygen uptake was higher than the preoperative value during the entire postoperative period. No correlations between thyroid hormones and catecholamines or cortisol or oxygen uptake were found. It is concluded that the most pronounced changes in thyroid hormones and TSH after upper abdominal surgery occur about 24 h postoperatively but catecholamines demonstrate their maximal increase immediately after surgery. The inverse correlation between T3 and catecholamines previously reported in burned patients, with their severe hypermetabolism, it is not present during the moderate hypermetabolism after abdominal surgery.


[The use of hemostatic agent Tachosil in surgical treatment of kidney cancer infiltrating liver--case report].
The right kidney cancer very rarely locally invades the liver as compared with blood metastasis which occur more frequent. In these cases, the only extensive surgical resection of part of the liver gives the opportunity to improve survival dependent on kidney cancer. In the intra-and postoperative bleeding and leakage of bile from the liver cut surface is a complication that it depends on the success of the treatment. A valuable complement to traditional ways of obtaining hemostasis is sealed section of liver collagen patches of horse, which are covered with tissue adhesive supplemented human fibrinogen and thrombin (Tachosil). The aim of this study is to present the case of 38-year-old woman with a tumor of the upper pole of the right kidney invasive by the continuity of the right lobe of liver, in which the classic methods of obtaining hemostasis supplemented using Tachosil postoperative course and a comparison with data from the literature. We demonstrated the usefulness of the application Tachosil sealing vascular suture in the vein cava inferior and obtain hemostasis and tissue sealing the right liver lobe cross-section area of about 250 cm2. After treatment, a patient had drainage from the site of the kidney comparable with data from the literature. Patient was discharged home on postoperative day 7 in good condition. Tachosil in major surgery because of locally advanced kidney cancer that invades the liver is a valuable complement to conventional surgical methods allowing for atraumatic stop bleeding and seal parenchymal liver tissue. Doing so helps to avoid early and late complications and reduce the cost of treating these complications.


Calculations to determine sample size.
Evidence-based care is currently being promoted in the NHS. The implications of this strategy are that nursing practice should be based on evidence rather than opinion or tradition. It is generally accepted that the strongest evidence is provided by a randomised controlled trial. In a randomised controlled trial two groups are involved, one of which receives a new treatment and one of which, the control group, receives a standard or alternative treatment. Ideally, tables of random numbers are used to allocate individual patients to the new treatment and the alternative treatment. In this context, treatment may include not only medication but also an educational or other therapeutic intervention. 'The method is thus widely applicable to nursing research.


Retinal vein occlusion and macular edema - critical evaluation of the clinical value of ranibizumab.
Retinal vein occlusions (RVOs) constitute the second most common cause of retinal vascular disease after diabetic retinopathy, with a prevalence of between 1% and 2% in persons older than 40 years of age. Despite the existence of numerous potential therapeutic options, none is entirely satisfactory, and many patients with RVO suffer irreversible visual loss. Fortunately however, the recent introduction of antivascular endothelial growth factor (VEGF) agents, such as ranibizumab (Lucentis(®), Genentech, South San Francisco, CA) and bevacizumab (Avastin(®), Genentech), offers a potentially new treatment approach for clinicians managing this disorder. The results of the BRAVO and CRUISE trials have provided the first definitive evidence for the efficacy and safety of ranibizumab in the treatment of RVO. As a result, ranibizumab has recently been approved by the US Food and Drug Administration for the treatment of RVO-associated macular edema. In this review, we provide a critical evaluation of clinical trial data for the safety and efficacy of ranibizumab, and address unresolved issues in the management of this disorder.


Testing the compatibility of a combination of tiamulin/chlortetracycline 1:3 premix (Tetramutin-Novartis) given in feed at different levels with salinomycin in chickens.
The compatibility of salinomycin (SA) (60 mg/kg feed) and Tetramutin (TM), a combination of tiamulin (TI) and chlortetracycline (CTC) in a 1:3 ratio, included in varying concentrations, was tested in broiler chickens. Assessment was based on clinical signs, body weight gain, feed conversion efficiency, gross pathological lesions and histological lesions in liver, heart and pectoral muscles, as well as analysis of blood for lactate dehydrogenase (LDH), aspartate dehydrogenase (AST) and creatine phosphokinase (CPK) activity. It was shown that chickens can be safely treated in feed for 7 days with TM containing TI concentrations of 33 or 55mg/kg feed together with SA at 60mg/kg. However, higher levels of TI (100 and 150 mg/kg feed) caused some adverse effects. There was no mortality but there was mild depression, 'leg weakness' accompanied by specific histological lesions in pectoral muscles (obliteration of cross-striation and swelling of muscle fibres, nuclei of muscle cells, hyalinization and destruction of sarcoplasm), a mild increase of AST activity, and a significant increase of CPK and LDH activity in blood. These latter two parameters can be used as an early indication of TI and SA incompatibility.


Familial non-Hodgkin lymphoma: histologic diversity and relation to other cancers.
Familial non-Hodgkin lymphoma (NHL) cases were classified according to the histologic criteria (modified) of Rappaport, to determine the extent of morphologic similarities of the tumors. In four families affected members had different tumor histologies that may be observed in an individual patient as the lymphoma progresses. In two families, the affected relatives had tumors of seemingly discordant histology. These tumors may nonetheless be etiologically related as indicated by the pattern of laboratory abnormalities, especially immunologic, in affected as well as unaffected members. The 20 cases had a reversal of the sex ratio (M/F) usually seen in NHL: 0.5 instead of 1.3. Other tumors observed in these families included primary hepatocellular carcinoma, pulmonary adenocarcinoma, Hodgkin disease, and acute lymphocytic leukemia - all of which have been associated with inborn or acquired immunodeficiency states.


A randomized, double-blind, placebo-controlled pilot trial of triiodothyronine in neonatal heart surgery.
This study was undertaken to evaluate the effect of triiodothyronine replacement on the early postoperative course of neonates undergoing aortic arch reconstruction. We performed a randomized, double-blind, placebo-controlled trial of triiodothyronine supplementation in neonates undergoing either a Norwood procedure or two-ventricle repair of interrupted aortic arch and ventricular septal defect. Patients were assigned to receive a continuous infusion of triiodothyronine (0.05 micro/kg/h) or placebo for 72 hours after cardiopulmonary bypass. Primary end points were a composite clinical outcome score and cardiac index at 48 postoperative hours. We enrolled 42 patients (triiodothyronine n = 22, placebo n = 20). Baseline characteristics were similar in the treatment groups. Study drug was discontinued prematurely because of hypertension (n = 1) and ectopic atrial tachycardia (n = 1), both cases in the triiodothyronine group. Free and total triiodothyronine levels were higher in the triiodothyronine group than in the placebo group at 24, 48, and 72 postoperative hours (P < .001). The median clinical outcome scores were 2.0 (range 0-4) with triiodothyronine and 2.0 (range 0-7) with placebo (P = .046). Compared with those in the placebo group, neonates assigned to triiodothyronine had shorter median time to negative fluid balance (2.0 vs 2.5 days, P = .027). Cardiac index values were 2.11 +/- 0.64 L/min x m2 with triiodothyronine and 2.05 +/- 0.72 L/min x m2 with placebo (P = .81). Heart rate and diastolic blood pressure were not influenced by triiodothyronine supplementation, but systolic blood pressure was higher in the triiodothyronine group (P < .001). No serious adverse events were attributed to triiodothyronine administration. Triiodothyronine supplementation was safe and resulted in more rapid achievement of negative fluid balance after aortic arch reconstruction. Cardiac index at 48 hours was not significantly improved.


[Anesthetic Management of Peritonectomy and Extended Operation for Peritoneal Pseudomyxoma Combined with Massive Ascites].
We report successful anesthetic management of extended operation for peritoneal pseudomyxoma combined with massive ascites (16.5 l). A 66-year-old man (weight 76 kg) who could not keep a supine position due to massive ascites associated with peritoneal pseudomyxoma was scheduled for elective peritonectomy and extended surgery. With the patient in the semisitting position, we administered 3% sevoflurane to induce loss of consciousness while preserving spontaneous ventilation. We then performed crush induction with propofol and rocuronium after topical anesthesia to the tongue base. Tracheal intubation with the Macintosh laryngoscope was successful. During the operation, we aspirated about 16.5 l of ascites over 20 l normal saline irrigation. To maintain the body temperature, we performed both active and passive extracorporeal warming. The operation included not only total peritonectomy but also distal gastrectomy, right colon resection, splenectomy, and cholecystectomy. To perform effective postoperative analgesia, we placed two epidural catheters from the upper and lower thoracic epidural spaces. The patient was extubated 3 days after operation, and discharged uneventfully on the 18th postoperative day.


Flexible microfabricated film sensors for the in situ quantum dot-based voltammetric detection of DNA hybridization in microwells.
A new flexible miniaturized integrated device was microfabricated for the in situ ultrasensitive voltammetric determination of DNA mutation in a microwell format, using quantum dots (QDs) labels. The integrated device consisted of thin Bi, Ag, and Pt films (serving as the working, reference, and counter electrode, respectively) deposited by sputtering on a flexible polyimide substrate. A DNA assay was employed in microwell format, where an immobilized complementary oligonucleotide probe hybridized with the biotinylated target oligonucleotide followed by reaction with streptavidin-conjugated PbS QDs. After the acidic dissolution of the QDs, the flexible sensor was rolled and inserted into the microwell and the Pb(II) released was determined in situ by anodic stripping voltammetry. Since the analysis took place directly in the microwell, the volume of the working solution was only 100 μL and the target DNA could be detected at a concentration down to 1.1 fmol L(-1). The proposed flexible microdevice addresses the restrictions of conventional rigid electrodes while it provides a low cost integrated transducer for the ultrasensitive detection of important biomolecules.


Fiberoptic oral intubation: the effect of model fidelity on training for transfer to patient care.
Previous studies have indicated that fiberoptic orotracheal intubation (FOI) skills can be learned outside the operating room. The purpose of this study was to determine which of two educational interventions allows learners to gain greater capacity for performing the procedure. Respiratory therapists were randomly assigned to a low-fidelity or high-fidelity training model group. The low-fidelity group was guided by experts, on a nonanatomic model designed to refine fiberoptic manipulation skills. The high-fidelity group practiced their skills on a computerized virtual reality bronchoscopy simulator. After training, subjects performed two consecutive FOIs on healthy, anesthetized patients with predicted "easy" intubations. Each subject's FOI was evaluated by blinded examiners, using a validated global rating scale and checklist. Success and time were also measured. Data were analyzed using a two-way mixed design analysis of variance. There was no significant difference between the low-fidelity (n = 14) and high-fidelity (n = 14) model groups when compared with the global rating scale, checklist, time, and success at achieving tracheal intubation (all P = not significant). Second attempts in both groups were significantly better than first attempts (P < 0.001), and there was no interaction between "fidelity of training model" and "first versus second attempt" scores. There was no added benefit from training on a costly virtual reality model with respect to transfer of FOI skills to intraoperative patient care. Second attempts in both groups were significantly better than first attempts. Low-fidelity models for FOI training outside the operating room are an alternative for programs with budgetary constraints.


Using ChatGPT to evaluate cancer myths and misconceptions: artificial intelligence and cancer information.
Data about the quality of cancer information that chatbots and other artificial intelligence systems provide are limited. Here, we evaluate the accuracy of cancer information on ChatGPT compared with the National Cancer Institute's (NCI's) answers by using the questions on the "Common Cancer Myths and Misconceptions" web page. The NCI's answers and ChatGPT answers to each question were blinded, and then evaluated for accuracy (accurate: yes vs no). Ratings were evaluated independently for each question, and then compared between the blinded NCI and ChatGPT answers. Additionally, word count and Flesch-Kincaid readability grade level for each individual response were evaluated. Following expert review, the percentage of overall agreement for accuracy was 100% for NCI answers and 96.9% for ChatGPT outputs for questions 1 through 13 (ĸ = ‒0.03, standard error = 0.08). There were few noticeable differences in the number of words or the readability of the answers from NCI or ChatGPT. Overall, the results suggest that ChatGPT provides accurate information about common cancer myths and misconceptions.


Common Adult Skin and Soft Tissue Lesions.
A strong foundational knowledge of dermatologic disease is crucial for a successful practice in plastic surgery. A plastic surgeon should be able to identify and appreciate common dermatologic diseases that may require medical and/or surgical evaluation and management. In this article, the authors describe epidermal/dermal, infectious, pigmented, and malignant cutaneous lesions that are commonly encountered in practice. Descriptions include the epidemiology, pathogenesis, clinical course, and management options for each type of lesion.


Anatomical organization of presubicular head-direction circuits.
Neurons coding for head-direction are crucial for spatial navigation. Here we explored the cellular basis of head-direction coding in the rat dorsal presubiculum (PreS). We found that layer2 is composed of two principal cell populations (calbindin-positive and calbindin-negative neurons) which targeted the contralateral PreS and retrosplenial cortex, respectively. Layer3 pyramidal neurons projected to the medial entorhinal cortex (MEC). By juxtacellularly recording PreS neurons in awake rats during passive-rotation, we found that head-direction responses were preferentially contributed by layer3 pyramidal cells, whose long-range axons branched within layer3 of the MEC. In contrast, layer2 neurons displayed distinct spike-shapes, were not modulated by head-direction but rhythmically-entrained by theta-oscillations. Fast-spiking interneurons showed only weak directionality and theta-rhythmicity, but were significantly modulated by angular velocity. Our data thus indicate that PreS neurons differentially contribute to head-direction coding, and point to a cell-type- and layer-specific routing of directional and non-directional information to downstream cortical targets.


Impact of the change of copay policy in Medicare Part D on zoster vaccine uptake among Medicare beneficiaries in a managed care organization.
Kaiser Permanente Southern California (KPSC) adopted the Medicare Part D Tier-6 with zero patient copay for zoster vaccination in 2012. We assessed the impact of the implementation on zoster vaccination rate (GSK study identifier: HO-13-14,182). Zoster vaccination rate was examined among an open cohort of ≥65-year-old Medicare Part D beneficiaries during 01/01/2008-06/30/2014, compared to ≥65-year-old commercial health plan members and 60-64-year-old members. The demographics, vaccination records, and insurance and benefit type were confirmed through KPSC electronic medical record databases. Person-time based vaccination rate was calculated for each observation interval (calendar month or year). The changes in annual rates in one year pre- (2011) and post- (2012) Tier-6 implementation were compared in a difference-in-difference analysis. Linear spline Poisson regression models were fitted to compare the secular trend of monthly rates during pre and post Tier-6 implementation (01/2012). Zoster vaccination rate increased in Medicare Part D beneficiaries after the implementation of zero copay. The increase in annual vaccination rate from 2011 to 2012 was marginally higher in Medicare Part D beneficiaries but not statistically significant (difference in rate ratio [RR] = 0.04, p > 0.05) compared to commercial health plan members. Among non-Hispanic white members, the difference of RR was 0.09 (p = 0.020) between Medicare Part D beneficiaries and ≥65-year-old commercial plan members, and it was 0.08 (p = 0.034) compared to 60-64-year-old commercial plan members. In secular trend analysis, we did not observe significant increase in overall and race stratified zoster vaccination rate attributable to the implementation of the Tier-6. The impact of Tier-6 on zoster vaccination was not substantial in elderly Medicare Part D beneficiaries in this population where a lower than average copay ($20 to $40) was applied prior to the Tier-6 implementation. Further research is necessary to explore the numerical relationship between vaccination and amount of copay. GSK study identifier: HO-13-14,182.


Temporal trends in stroke incidence in South Asian, Chinese and white patients: A population based analysis.
Little is known about potential ethnic differences in stroke incidence. We compared incidence and time trends of ischemic stroke and primary intracerebral hemorrhage in South Asian, Chinese and white persons in a population-based study. Population based census and administrative data analysis in the provinces of Ontario and British Columbia, Canada using validated ICD 9/ICD 10 coding for acute ischemic and hemorrhagic stroke (1997-2010). There were 3290 South Asians, 4444 Chinese and 160944 white patients with acute ischemic stroke and 535 South Asian, 1376 Chinese and 21842 white patients with intracerebral hemorrhage. South Asians were younger than whites at onset of stroke (70 vs. 74 years for ischemic and 67 vs. 71 years for hemorrhagic stroke). Age and sex adjusted ischemic stroke incidence in 2010 was 43% lower in Chinese and 63% lower in South Asian than in White patients. Age and sex adjusted intracerebral hemorrhage incidence was 18% higher in Chinese patients, and 66% lower in South Asian relative to white patients. Stroke incidence declined in all ethnic groups (relative reduction 69% in South Asians, 25% in Chinese, and 34% in white patients for ischemic stroke and for intracerebral hemorrhage, 79% for South Asians, 51% for Chinese and 30% in white patients). Although stroke rates declined across all ethnic groups, these rates differed significantly by ethnicity. Further study is needed to understand mechanisms underlying the higher ischemic stroke incidence in white patients and intracerebral hemorrhage in Chinese patients.


Effect of tumour promoters and non-genotoxic carcinogens on terminal differentiation and proliferation in mouse teratoma XB2 cells cultured in low calcium medium.
XB2 cells, a teratocarcinoma derived cell line of keratinocyte lineage, have been shown to proliferate and differentiate in low calcium medium (0.03 mM Ca2+) at a density of 500 cells/9.6 cm2 without the need for fibroblast feeder layers or conditioned medium. The degree of differentiation can be assessed by measurements of keratin production and stratification of colonies of cells. Both of these parameters, as well as the proliferative capacity of the cells, can be altered by treatment of the cultures with various promoting agents and non-genotoxic carcinogens. Treatment with teleocidin and 12-O-tetradecanoyl phorbol-13-acetate induced large increases in proliferation, stratification and keratinization; mezerein-treated cells showed increased stratification at higher doses; butylated hydroxyanisole treatment resulted in hyperkeratinization and hyperstratification to lower levels than that seen with the phorbol-ester-like promoters; butylated hydroxytoluene had purely hyperproliferative effects. We suggest that this culture system may provide a useful model for studies of the mechanism of promotion and non-genotoxic carcinogenesis in epithelial tissues.


SIK1 suppresses colorectal cancer metastasis and chemoresistance via the TGF-β signaling pathway.
In the present study, we investigated the role of salt-induced kinase 1 (SIK1), a serine/threonine kinase protein, in colorectal cancer (CRC). Despite the reported association of SIK1 with tumor malignancy suppression in various cancers, limited research has been conducted on its function in CRC. Our findings revealed that SIK1 expression was low in CRC cells. The results of a KEGG pathway analysis showed a strong association between SIK1 and the TGF-β signaling pathway. In addition, a coimmunoprecipitation assay validated the interaction between SIK1 and Smad7. Our data indicate that SIK1 inhibited the phosphorylation of Smad2, a critical molecule in the Smad-related TGF-β pathway, and downstream target genes of the TGF-β pathway. Furthermore, SIK1 was found to inhibit indicators of epithelial-mesenchymal transition (EMT) and reverse oxaliplatin resistance in CRC. Additionally, SIK1 reduced cell migration and invasion. Our results suggest that the inhibitory effect of SIK1 on the TGF-β pathway contributes to the suppression of metastasis and oxaliplatin chemoresistance in CRC. However, this effect was reversed by galunisertib (LY2157299). In conclusion, our findings provide novel insights into the role of SIK1 in the regulation of the TGF-β pathway in CRC, suggesting its potential as a therapeutic target for the treatment of CRC. Further studies are required to fully characterize the mechanism underlying these observations and to validate these findings in animal models.


Exosomes transfer miRNAs from cell-to-cell to inhibit autophagy during infection with Crohn's disease-associated adherent-invasive E. coli.
Adherent-invasive E. coli (AIEC), which abnormally colonize the intestinal mucosa of Crohn's disease (CD) patients, are able to adhere to and invade intestinal epithelial cells (IECs), survive and replicate within macrophages and induce a pro-inflammatory response. AIEC infection of IECs induces secretion of exosomes that increase AIEC replication in exosome-receiving IECs and macrophages. Here, we investigated the mechanism underlying the increased AIEC replication in cells receiving exosomes from AIEC-infected cells. Exosomes released by uninfected human intestinal epithelial T84 cells (Exo-uninfected) or by T84 cells infected with the clinical AIEC LF82 strain (Exo-LF82), the nonpathogenic E. coli K12 strain (Exo-K12) or the commensal E. coli HS strain (Exo-HS) were purified and used to stimulate T84 cells. Stimulation of T84 cells with Exo-LF82 inhibited autophagy compared with Exo-uninfected, Exo-K12 and Exo-HS. qRT-PCR analysis revealed increased levels of miR-30c and miR-130a in Exo-LF82 compared to Exo-uninfected, Exo-K12 and Exo-HS. These miRNAs were transferred via exosomes to recipient cells, in which they targeted and inhibited ATG5 and ATG16L1 expression and thereby autophagy response, thus favoring AIEC intracellular replication. Inhibition of these miRNAs in exosome-donor cells infected with AIEC LF82 abolished the increase in miR-30c and miR-130a levels in the released Exo-LF82 and in Exo-LF82-receiving cells, thus suppressing the inhibitory effect of Exo-LF82 on ATG5 and ATG16L1 expression and on autophagy-mediated AIEC clearance in Exo-LF82-receiving cells. Our study shows that upon AIEC infection, IECs secrete exosomes that can transfer specific miRNAs to recipient IECs, inhibiting autophagy-mediated clearance of intracellular AIEC.


Evaluation of renal oxidative stress in the development of DOCA-salt induced hypertension and its renal damage.
To ascertain the onset of renal oxidative stress and its interrelation with the increase in blood pressure (BP) and kidney injury in rats subjected to Deoxycorticosterone (DOCA)-salt treatment, BP, renal antioxidants, renal damage indices, and histological changes were studied weekly. In the two other groups, 200 mg/kg/day vitamin E or C were co-administered with DOCA-salt for 4 weeks. Blood Pressure was increased at week one. Urinary N-acetyl-B-diglucosaminidase (NAG) and proteinuria increased and renal catalase decreased at 2nd week. Histological changes and decreased glothatione (GSH) and Ferric reducing antioxidant power (FRAP) were demonstrated at three week. Vitamin therapy increased renal antioxidants and decreased BP, NAG, proteinuria, and histological damage. Thus, elevation in BP precedes the onset of renal oxidative stress in DOCA-salt treated rats. Enhanced renal oxidative stress contributes to kidney damage. In this study, treatment with vitamin C or vitamin E preserved renal antioxidant levels, prevented renal damage, and partially inhibited elevation of BP in the DOCA-salt treatment.


A meta-analysis of prophylactic endoscopic sclerotherapy for esophageal varices.
A number of randomized clinical trials of prophylactic sclerotherapy have been carried out with different results. The main objective of this study was to determine if the literature provides evidence that prophylactic sclerotherapy increases the survival rate of patients with esophageal varices. Meta-analysis was used to evaluate the effect of prophylactic sclerotherapy on the survival of patients with esophageal varices. Only randomized controlled trials that compared prophylactic sclerotherapy to placebo were included. Fourteen fully published randomized controlled trials, as well as six trials published as abstracts, were identified in the English literature. Pooling of the 14 fully published trials yielded an odds ratio of death in the treatment group compared with the control group of 0.74 (95% confidence interval, 0.60-0.93) in favor of prophylactic sclerotherapy. There was statistically significant heterogeneity that resolved when the trials were pooled in subgroups based on the sclerosant used. Pooling of trials using polidocanol showed a highly significant benefit for prophylactic sclerotherapy in terms of overall mortality, particularly when those trials that selected subjects at high risk of bleeding were pooled, yielding an odds ratio of 0.51 (95% confidence interval, 0.36-0.73). When trials using sodium tetradecyl sulfate were pooled, a detrimental effect for prophylactic sclerotherapy was seen, with an odds ratio of 1.86 (95% confidence interval, 1.15-3.00). Subgroup analysis by Child's class showed no benefit for patients in Child's class A. These results suggest that prophylactic sclerotherapy with polidocanol is effective, particularly in high-risk patients.


Effect of the essential amino acid-nitrogen to total nitrogen ratio on lysine requirement for nitrogen retention in growing pigs.
Low protein diets supplemented with essential amino acids (EAA) fed to pigs reduce the excess supply of EAA and nitrogen (N). However, low protein diets may become limiting in non-essential amino acids (NEAA) and N, thus affecting the utilization of EAA for N retention. It has been suggested that the EAA-N:total N (E:T) ratio can give an indication of dietary N sufficiency. An N-balance study was conducted to determine the effect of E:T ratio on the Lys requirement for maximum N retention. A total of 80 growing barrows (19.3 ± 0.21 kg initial body weight) were randomly assigned to 1 of 10 diets (n = 8) in 8 blocks in a 2 × 5 factorial arrangement. Diets consisted of a low ratio (LR; E:T of 0.33) or a high ratio (HR; E:T of 0.36) with graded Lys content (0.82%, 0.92%, 1.02%, 1.12%, and 1.22% standardized ileal digestible [SID]). After a 7-d adaptation, a 4-d N-balance collection was conducted. Blood samples were obtained on d 2 of the collection period 2 h after the morning meal for plasma urea N (PUN) analysis. Data were analyzed using the MIXED model procedure with fixed effects of ratio (n = 2), Lys (n = 5), and their interactions. The experimental block (room) was included as a random effect (n = 8). The SID Lys requirement was estimated using PROC NLIN linear broken-line breakpoint model. There was a significant interaction between E:T ratio and Lys (P < 0.01), where LR diets had a higher N retention than HR diets, while increasing Lys linearly increased N retention (P = 0.01) in both HR and LR diets. The marginal efficiency of utilizing SID Lys (P < 0.01) reduced with increasing Lys content, while the efficiency of utilizing N (P < 0.05) increased as Lys increased. The SID Lys required to maximize N retention of pigs fed HR diets was estimated at 1.08% (R2 = 0.61) and LR diets at 1.21% (R2 = 0.80). The current results indicate that N may be limiting in diets with a high E:T ratio, limiting N retention. Supplying additional dietary N, as intact protein, can increase N retention, resulting in a greater Lys requirement.


Religious/spiritual struggles and psychological distress: A test of three models in a longitudinal study of adults with chronic health conditions.
This study tested three conceptual explanatory models that have been theorized to account for the linkages between religious/spiritual (R/S) struggles and psychological distress: the primary model (i.e., R/S struggles lead to psychological distress), the secondary model (i.e., psychological distress leads to R/S struggles), and the complex model (i.e., R/S struggles and psychological distress reciprocally exacerbate each other). Using prospective data from a sample of US adults living with chronic health conditions (n = 302), we performed a cross-lagged panel analysis with three timepoints to test for evidence of potential causal relations between R/S struggles and psychological distress. Consistent with the complex conceptual model of R/S struggles, we found evidence of positive reciprocal associations between R/S struggles and psychological distress. The findings highlight the importance of attending to the dynamic interplay between R/S struggles and psychological distress when working with adults who have chronic health conditions.


The pattern of intussusception in Kuwait. A review of 244 cases.
Two-hundred and thirty-three patients with 244 intussusceptions were treated in the Department of Paediatric Surgery, Ibn Sina Hospital, Kuwait, with only one death. Our incidence was around 25 per year. The age for idiopathic intussusception fits that reported in Western countries. Kuwaitis have a lower incidence of intussusception than other nationalities living in Kuwait. Diarrhea seems to precede intussusception in about 19.1% of cases; leading points were found in 8.2%, and recurrences in 4.5% of cases, most of them following barium reduction. Our complications were high, particularly in the operated group. Barium enema has become our first line of management and it has greatly reduced complications and shortened hospitalization times. Those who present early and late are more prone to operative treatment.


Non-invasive prenatal paternity testing using a standard forensic genetic massively parallel sequencing assay for amplification of human identification SNPs.
Prenatal paternity testing often relies on invasive procedures that cause risk to both the mother and the foetus. Non-invasive, prenatal paternity testing by investigating paternally inherited single nucleotide polymorphisms (SNPs) in cell-free foetal DNA (cffDNA) in maternal plasma was performed at consecutive time points during early gestation. Plasma from 15 pregnant women was investigated at consecutive time points from gestational weeks (GWs) 4-20. The Precision ID Identity Panel and an Ion S5 Sequencer was used to analyse the cffDNA. Paternally inherited foetal SNP alleles were detected from GW7. The median foetal fractions were 0%, 3.9%, 5.1%, 5.2%, and 4.7% at GWs 4, 7, 12, 16, and 20, respectively. The corresponding median numbers of detected paternally inherited foetal autosomal SNP alleles were 0, 3, 9, 10, and 12, respectively. The typical (i.e. geometric mean) paternity indices at GW12 and GW20 were 24 (range 0.0035-8389) and 199 (range 5.1-30,137), respectively. The method is very promising. However, the method can be improved by shortening the lengths of the PCR amplicons and increasing the number of SNPs. To our knowledge, this is the first study to successfully identify paternally inherited foetal SNP alleles at consecutive time points in early gestation independently of the foetal gender.


Prenatal marijuana exposure impacts executive functioning into young adulthood: An fMRI study.
Understanding the potentially harmful long term consequences of prenatal marijuana exposure is important given the increase in number of pregnant women smoking marijuana to relieve morning sickness. Altered executive functioning is one area of research that has suggested negative consequences of prenatal marijuana exposure into adolescence. Investigating if these findings continue into young adulthood and exploring the neural basis of these effects was the purpose of this research. Thirty one young adults (ages 18-22years) from the longitudinal Ottawa Prenatal Prospective Study (OPPS) underwent functional magnetic resonance imaging (fMRI) during four tasks; 1) Visuospatial 2-Back, 2) Go/NoGo, 3) Letter 2-Back and 4) Counting Stroop task. Sixteen participants were prenatally exposed to marijuana while 15 had no prenatal marijuana exposure. Task performance was similar for both groups but blood flow was significantly different between the groups. This paper presents the results for all 4 tasks, highlighting the consistently increased left posterior brain activity in the prenatally exposed group compared with the control group. These alterations in neurophysiological functioning of young adults prenatally exposed to marijuana emphasizes the importance of education for women in child bearing years, as well as for policy makers and physicians interested in the welfare of both the pregnant women and their offspring's future success.


[Myelodysplastic/myeloproliferative neoplasm: a histopathological review].
Myelodysplastic syndromes/myeloproliferative neoplasm (MDS/MPN) is a type of myeloid neoplasm where at least one hematopoietic lineage exhibiting cytopenia clinically coexists with other (s) exhibiting hypercytosis. There is ineffective erythropoiesis and bone marrow coexistence of at least one hematopoietic lineage morphologically characterized by dysplasia of blood cells and other (s) characterized by pronounced proliferation. At a molecular level, various abnormalities have been identified that overlap with related diseases, and a prerequisite for MDS/MPN diagnosis includes ruling out various hematopoietic tumors and reactive conditions. Therefore, a multilateral approach involving clinical findings, morphology, and molecular biology is needed. Herein, we introduce the pathological features of MDS/MPN and the relationship between molecular abnormalities and morphological characteristics.


Haemophagocytic lymphohistiocytosis in a preterm infant: A case report.
Haemophagocytic lymphohistiocytosis (HLH) is a rare disease with a sepsis-like progression that leads to multiple organ dysfunction syndrome, especially in preterm infants. We present herein a case of HLH in a premature infant presenting with disseminated intravascular coagulopathy (DIC) and liver failure. A male infant, with weight 810g and delivered at the gestational age of 25 weeks and 2 days, was misdiagnosed with tyrosinaemia for several weeks. He presented with anaemia, thrombocytopaenia, persistent DIC, and elevated liver enzymes despite continuous transfusion and broad-spectrum antibiotics. A bone marrow puncture biopsy revealed haemophagocytosis, leading to HLH diagnosis. It is important for paediatricians to consider the possibility of HLH when liver function test results are abnormal in such patients.


Serotypes, virulence genes and polymorphism of capsule gene cluster in Lactococcus garvieae isolated from diseased rainbow trout (Oncorhynchus mykiss) and mugger crocodile (Crocodylus palustris) in Iran.
Lactococcus garvieae causes lactococcosis in rainbow trout in many parts of the world. This study was conducted for the existence of the virulent factors and differentiation of the two serotypes in L. garvieae. Twenty-two strains of L. garvieae isolated from diseased rainbow trout from farms in different regions and mugger crocodile of Iran, were investigated. In order to rapidly detect the presence of the hly1, hly2, hly3, NADH oxidase, sod, pgm, adhPsaA, eno, LPxTG-3, adhCI, and adhCII virulence genes, two multiplex polymerase chain reaction (PCR) assays were developed. Also, simplex PCR method was used to identify the bacterial serotypes, CGC, LPxTG-2, Adhesion, and adhPav virulence genes using the specific primer. All varieties of L. garvieae contained the hly1, hly2, hly3, NADH oxidase, pgm, adhPav, LPxTG-3, sod, eno, adhPsaA, adhCI, and CGC virulence genes. Also, adhCII gene was present in all strains except one of the isolates originated from mugger crocodile. In addition, LPxTG-2 gene was only present in one of the isolates belonging to mugger crocodile. Adhesion gene was not present in all the strains. Interestingly, all the 22 strains originated from both hosts were identified as belonging to the serotype I. Based on the phylogenetic sequences of the capsule gene cluster, group all fish isolates into a cluster together with one isolate obtained from mugger crocodile. Further studies are recommended to investigate the role of virulence genes in L. garvieae and evaluate their pathogenicity to rainbow trout.


The Secret Life of Junior Pathologists.
Transition from pathology trainee to independent pathologist is stressful. No study has examined junior pathologists' challenges and concerns during this transition. To identify challenges and concerns of junior pathologists. Junior pathologists were defined as those who had been practicing independently for up to 5 years after completion of residency/fellowship. An institutional review board-approved electronic survey was created and distributed to recent pathology graduates of MD Anderson Cancer Center (Houston, Texas) and MedStar Georgetown University Hospital (Washington, District of Columbia). The survey was open from October 13, 2022, to January 31, 2023. The survey included 16 multiple-choice and free-text questions. Responses were received from 39 junior pathologists. Participants working in academic settings indicated independence, work-life balance, and professional identity formation as challenges; those in nonacademic settings indicated pathology reporting, efficiency, and administration as challenges. Areas where participants wished they received more guidance differed by practice setting: participants in academic settings more often chose effective time management and importance of turnaround time (35% [7 of 20] versus 0% [0 of 14], P = .03) and tumor board conference presentation skills (25% [5 of 20] versus 0% [0 of 14], P = .06), while those in nonacademic settings more often chose current procedural terminology (CPT) coding, billing, and cost-effective patient care (79% [11 of 14] versus (35% [7 of 20]; P = .02). More female than male participants indicated that they wished they had received more guidance in leadership and soft skills (79% [11 of 14] versus 28% [5 of 18]; P = .01). This study identified challenges experienced by junior pathologists. Collective efforts from training programs, experienced pathologists, and professional organizations can explore ways to improve the transition experience.


Sharing the burden: A neutral approach to socioecological theory.
The socioecological model (SEM) is a popular collection of controversial models purporting to explain mating systems in terms of ecological and social parameters. Despite its guise of objectivity, several of its hypotheses assume Victorian gender stereotypes of active, competing males heedlessly sowing their seeds, and cautious, passive females, imprisoned by greater costs of reproduction and their consequent resourceߚdependence. We enter this debate by taking a previously neglected explanatory approach borrowed from species theory. According to the Recognition Concept of sexual species, the unit of reproductive success/fitness is irreducible to fewer than two integrated subparts (minimally a male and a female). Phyletic changes in mating systems logically effect changes in fertilization systems, leading to reproductive isolation. We take our primary assumption of the average equivalence of female and male contributions to successful reproduction from the writings of the natural philosopher, Antoinette Blackwell. We revisit the SEM with its contradictions and extrapolations, and develop a genderߚneutral alternative hypothesis termed SpecificߚMate Contact (SMC), centered on two fundamental mating strategies: sexual animals may behave as synchronous mateߚattractors or asynchronous mateߚseekers, generating four possible mating system combinations (monogamy: two attractors; promiscuity: two seekers; polygyny: male attractor and female seeker; polyandry: female attractor and male seeker). Our approach predicts all known primate mating systems using a neutral (nonߚsexist) principle. The approach is also neutral in the sense that it does not invoke either competition or cooperation: fertilization success is considered a posteriori and males and females are coߚadapted to this end rather than cognitively cooperative.


Wide-field X-ray tube comparisons.
X-ray tubes having similar resolution capabilities along the central ray were compared for their wide-field characteristics. It has been suggested that focal spot size, and therefore resolution capability, along the cathode-anode axis may vary in a manner which is dependent upon the tube target angle. The authors show that differences beyond the effects of target angle occur, the extent of those differences varying from tube to tube. Although 2 different-sized focal spots may be adjusted to have equivalent central beam resolution capabilities, they can exhibit different imaging capabilities at wide-angle (off central axis) position. More than one parameter (equivalent focal spot size) is needed to characterize the behavior of a focal spot.


Is respiratory activity in the brain mitochondria responsive to thyroid hormone action?: a critical re-evaluation.
The effects of in vivo treatment with graded doses (0.5-1.5 micrograms/g body weight) of thyroid hormones, tri-iodothyronine (T3) and thyroxine (T4), for 4 consecutive days to euthyroid rats on the respiratory activity of isolated brain mitochondria were examined. T4 stimulated coupled State-3 respiration with glutamate, pyruvate + malate, ascorbate + tetramethyl-p-phenylenediamine and succinate, in a dose-dependent manner; T3 was effective only at the highest (1.5 micrograms) dose employed. T4 was more effective than T3 in stimulating respiratory activity. State-4 respiratory rates were in general not influenced except in the case of the ascorbate + tetramethyl-p-phenylenediamine system. Primary dehydrogenase activities, i.e. glutamate dehydrogenase, malate dehydrogenase and succinate dehydrogenase, were stimulated about 2-fold; interestingly mitochondrial but not cytosolic malate dehydrogenase activity was influenced under these conditions. The hormone treatments did not greatly influence the mitochondrial cytochrome content. The results therefore suggest that thyroid hormone treatment not only stimulates primary dehydrogenase activities but may also directly influence the process of mitochondrial electron transfer.


The treatment of infantile embryonal carcinoma (Yolk-Sac Tumour) of the testis in children.
The case histories of five patients with an infantile embryonal carcinoma are presented. Personal observations and data from the literature indicate that treatment of this tumour is dependent on the patient's age. Non-operative staging is possible under age 1 (alpha 1-foetoprotein and CT-scan). Staging should include a laparotomy in patients aged between 1 and 2 years. Under age 2, retroperitoneal lymph node dissection is indicated only if metastases are demonstrable. From age 2 on, retroperitoneal lymph node dissection should be performed if possible: unilaterally in the absence, and bilaterally in the presence of retroperitoneal metastases. Chemotherapy is required only in cases with metastases. Radiotherapy is not indicated in the treatment of infantile embryonal carcinoma.


Could incommensurability in sulfosalts be more common than thought? The case of meneghinite, CuPb13Sb7S24.
The structure of meneghinite (CuPb13Sb7S24), from the Bottino mine in the Apuan Alps (Italy), has been solved and refined as an incommensurate structure in four-dimensional superspace. The structure is orthorhombic, superspace group Pnma(0β0)00s, cell parameters a = 24.0549 (3), b = 4.1291 (6), c = 11.3361 (16) Å, modulation vector q = 0.5433 (4)b*. The structure was refined from 6604 reflections to a final R = 0.0479. The model includes modulation of both atomic positions and displacement parameters, as well as occupational waves. The driving forces stabilizing the modulated structure of meneghinite are linked to the occupation modulation of Cu and some of the Pb atoms. As a consequence of the Cu/[] and Pb/Sb modulations, three- to sevenfold coordinations of the M cations (Pb/Sb) occur in different parts of the structure. The almost bimodal distribution of the occupation of Cu/[] and Pb/Sb at M5 conforms with the coupled substitution Sb3+ + [] → Pb2+ + Cu+, thus corroborating the hypothesis deduced previously for the incorporation of copper in the meneghinite structure. The very small departure (∼0.54 versus 0.50) from the commensurate value of the modulation raises the question of whether other sulfosalts considered superstructures have been properly described, and, in this light, if incommensurate modulation in sulfosalts could be much more common than thought.


Blended Learning Educational Format for Third-Year Pediatrics Clinical Rotation.
Traditional medical education is shifting to incorporate learning technologies and online educational activities with traditional face-to-face clinical instruction to engage students, especially at remote clinical training sites. To describe and evaluate the effectiveness of the blended learning format (combining online and face-to-face instruction) for third-year osteopathic medical students during their pediatric rotation. Third-year medical students who completed the 4-week clerkship in pediatrics during the 2014-2015 academic year were divided into a standard learning group and a blended learning group with online activities (discussion boards, blogs, virtual patient encounters, narrated video presentations, and online training modules). Comprehensive Osteopathic Medical Achievement Test scores and final course grades were compared between the standard learning and blended learning groups. Students in the blended learning group completed a postsurvey regarding their experiences. Of 264 third-year students who completed the 4-week clerkship in pediatrics during the 2014-2015 academic year, 78 (29.5%) participated in the blended learning supplement with online activities. Of 53 students who completed the postsurvey in the blended learning group, 44 (83.0%) agreed or strongly agreed that "The integration of e-learning and face-to-face learning helped me learn pediatrics." Open-ended comments supported this overall satisfaction with the course format; however, 26 of 100 comments reflected a desire to increase the amount of clinical exposure and face-to-face time with patients. No statistical differences were seen between the standard learning (n=186) and blended learning (n=78) groups with regard to Comprehensive Osteopathic Medical Achievement Test scores (P=.321). Compared with the standard learning group, more students in the blended learning group received a final course grade of honors (P=.015). Results of this study support the use of blended learning in a clinical training environment. As more medical educators use blended learning, it is important to investigate the best balance between learning with technology and learning in a face-to-face setting. Online activities may enhance but should never fully replace face-to-face learning with real patients.


The functional role of integrins during intra- and extravasation within the metastatic cascade.
Formation of distant metastases is by far the most common cause of cancer-related deaths. The process of metastasis formation is complex, and within this complex process the formation of migratory cells, the so called epithelial mesenchymal transition (EMT), which enables cancer cells to break loose from the primary tumor mass and to enter the bloodstream, is of particular importance. To break loose from the primary cancer, cancer cells have to down-regulate the cell-to-cell adhesion molecuIes (CAMs) which keep them attached to neighboring cancer cells. In contrast to this downregulation of CAMS in the primary tumor, cancer cells up-regulate other types of CAMs, that enable them to attach to the endothelium in the organ of the future metastasis. During EMT, the expression of cell-to-cell and cell-to-matrix adhesion molecules and their down- and upregulation is therefore critical for metastasis formation. Tumor cells mimic leukocytes to enable transmigration of the endothelial barrier at the metastatic site. The attachment of leukocytes/cancer cells to the endothelium are mediated by several CAMs different from those at the site of the primary tumor. These CAMs and their ligands are organized in a sequential row, the leukocyte adhesion cascade. In this adhesion process, integrins and their ligands are centrally involved in the molecular interactions governing the transmigration. This review discusses the integrin expression patterns found on primary tumor cells and studies whether their expression correlates with tumor progression, metastatic capacity and prognosis. Simultaneously, further possible, but so far unclearly characterized, alternative adhesion molecules and/or ligands, will be considered and emerging therapeutic possibilities reviewed.


Mammary carcinoma. Comparison of nuclear DNA content from in situ and infiltrative components.
Twenty-eight mammary carcinomas were analyzed with respect to their nuclear DNA content. Ten of the carcinomas were entirely in situ (noninfiltrative) while 18 showed areas of both infiltrative and noninfiltrative growth. The DNA content of individual tumor cells was measured in sections from the original paraffin-embedded specimens. In the tumors that had noninfiltrative as well as infiltrative zones, DNA analyses were performed in both areas. Comparison between the DNA patterns obtained from these different areas of the same tumor showed very close agreement. Both groups of tumors (those with and those without areas of invasion) contained some cases that showed a euploid DNA pattern and some cases that showed an aneuploid pattern. Furthermore, analysis of the DNA content of regional lymph node metastases in seven of the invasive cases did not show an increased aneuploidy in the metastases. The results suggest that, in mammary carcinomas, invasive and noninvasive tumors cannot be distinguished by DNA analysis and that tumor progression does not seem to be associated with a significant alteration of the nuclear DNA content.


Gonadotropin-releasing hormone induces oscillatory membrane currents in rat gonadotropes.
Electrophysiological studies were performed to characterize membrane currents of rat gonadotropes under basal conditions and after exposure to secretagogues. Gonadotropes were identified in primary cultures of rat anterior pituitaries by a reverse hemolytic plaque assay. Giga-seal patch clamp recording with the cell-attached configuration was used to monitor membrane currents in these cells. Spontaneous spikes in basal current were seen. These were blocked by methoxyverapamil and probably reflect Ca2+-dependent action potentials. Brief GnRH stimulation induced slow oscillatory changes in membrane current that evolved into a series of large amplitude inward pulses after about 8 min. Treatment with TRH had no effect, and depolarization with K+ led to delayed inward currents without any oscillatory behavior. Under conditions of Ca2+ channel blockade, GnRH stimulation did not induce pulses of inward current, but did lead to oscillatory activation of a small conductance ion channel apparently selective for K+. Taken together these results suggest that GnRH induces oscillations in intracellular Ca2+ and that these oscillations are controlled by biochemical processes.


Machine Learning Reveals Synovial Fibroblast Genes Associated with Pain Affect Sensory Nerve Growth in Rheumatoid Arthritis.
It has been presumed that rheumatoid arthritis (RA) joint pain is related to inflammation in the synovium; however, recent studies reveal that pain scores in patients do not correlate with synovial inflammation. We identified a module of 815 genes associated with pain, using a novel machine learning approach, Graph-based Gene expression Module Identification (GbGMI), in samples from patients with longstanding RA, but limited synovial inflammation at arthroplasty, and validated this finding in an independent cohort of synovial biopsy samples from early, untreated RA patients. Single-cell RNA-seq analyses indicated these genes were most robustly expressed by lining layer fibroblasts and receptor-ligand interaction analysis predicted robust lining layer fibroblast crosstalk with pain sensitive CGRP+ dorsal root ganglion sensory neurons. Netrin-4, which is abundantly expressed by lining fibroblasts and associated with pain, significantly increased the branching of pain-sensitive CGRP+ neurons in vitro . We conclude GbGMI is a useful method for identifying a module of genes that associate with a clinical feature of interest. Using this approach, we find that Netrin-4 is produced by synovial fibroblasts in the absence of inflammation and can enhance the outgrowth of CGRP+ pain sensitive nerve fibers. Machine Learning reveals synovial fibroblast genes related to pain affect sensory nerve growth in Rheumatoid Arthritis addresses unmet clinical need.


Rounding of first order transitions in low-dimensional quantum systems with quenched disorder.
We prove that the addition of an arbitrarily small random perturbation to a quantum spin system rounds a first-order phase transition in the conjugate order parameter in d < or = 2 dimensions, or for cases involving the breaking of a continuous symmetry in d < or = 4. This establishes rigorously for quantum systems the existence of the Imry-Ma phenomenon which for classical systems was proven by Aizenman and Wehr.


Core diameter of bone marrow aspiration devices influences cell density of bone marrow aspirate in patients with severe peripheral artery disease.
Bone marrow (BM) transplantations are an accepted therapeutic strategy for hematologic conditions. In the past decades, interest for BM-derived cell therapy has extended toward the field of regenerative medicine. Irrespective of the treatment strategy, its success depends on the amount of cells available for transplantation. Both patient and procedural factors have been shown to influence the cell density of the BM aspirate. In the present study, the influence of core diameter of the BM aspiration device on cell density of the BM aspirate is studied. BM harvesting procedures performed in a clinical trial investigating the effect of BM cell therapy in patients with severe peripheral artery disease were retrospectively studied (clinicaltrials.gov NCT00371371). Patients underwent BM harvesting through the use of either a 15-gauge (n = 85) or an 8-gauge (n = 75) needle. The numbers of harvested white blood cells (WBC) and CD34(+) hematopoietic cells (HPC) were quantified. The amount of WBC per milliliter of BM aspirate was significantly higher when the 8-gauge needle (27.8 × 10(6) WBC/mL [95%CI 25.4-30.5 × 10(6)]) was used compared with the smaller 15-gauge core needle (20.1 × 10(6) WBC/mL [95% confidence interval (CI), 18.7-21.7 × 10(6)], P < 0.001). For the amount of CD34(+) HPC, a similar pattern was observed (185 × 10(3) HPC/mL [95% CI, 161-213 × 10(3)]; 114 × 10(3) HPC/mL [95% CI, 96-134 × 10(3)]; P < 0.001). The application of a BM aspiration device with a larger core diameter is associated with an increased cell density of the BM aspiration product in patients with severe peripheral artery disease.


Are microplastics in aquaculture an undeniable driver in accelerating the spread of antibiotic resistance genes?
Aquaculture products have been a key source of protein in the human food supply. Contamination by microplastics and antibiotic resistance genes (ARGs) directly affects food quality and safety. Plastic fishing gear and the long-term misuse of antibiotics result in the persistent residue, migration, and spread of microplastics and ARGs in the aquaculture environment, causing in ecological imbalance and endangering human security. Microplastics can act as "petri dishes" for the reproduction, communication, and spread of ARGs, which adds an additional layer of complexity to the global issues surrounding microplastics and ARGs. Aquaculture has become an important source of microplastics and ARGs in natural waters. Accordingly, this paper mainly discusses the contribution of aquaculture to the presence of microplastics and ARGs in aquatic ecosystems. Microplastics and ARGs can (1) affect the production and quality of aquatic products; (2) influence the development and reproduction of aquatic organisms; and (3) accelerate the spread of resistant bacteria. How to eliminate microplastics and ARGs and block their transmission has become a worldwide problem. Actually, further research is required to understand the scale and scope of these effects.


The Impact of Radiation on the Tumor Microenvironment: Effect of Dose and Fractionation Schedules.
In addition to inducing lethal DNA damage in tumor and stromal cells, radiation can alter the interactions of tumor cells with their microenvironment. Recent technological advances in planning and delivery of external beam radiotherapy have allowed delivery of larger doses per fraction (hypofractionation) while minimizing dose to normal tissues with higher precision. The effects of radiation on the tumor microenvironment vary with dose and fractionation schedule. In this review, we summarize the effects of conventional and hypofractionated radiation regimens on the immune system and tumor stroma. We discuss how these interactions may provide therapeutic benefit in combination with targeted therapies. Understanding the differential effects of radiation dose and fractionation can have implications for choice of combination therapies.


A birth-weight questionnaire indicated that life style modifies the birth weight and metabolic syndrome relationship at age 36.
Investigating the relationship between birth weight and the metabolic syndrome and the modifying effects of lifestyle in adults (36.5 years). 273 subjects completed a birth-weight questionnaire; waist circumference, HDL and triglyceride concentrations, blood pressure and HbA1c, physical activity and fitness, smoking status and dietary intake were measured. Risks for the metabolic syndrome and for having at least two of the components of the metabolic syndrome were calculated and the modifying effect of lifestyle factors was assessed by comparing four groups based on birth weight and a lifestyle factor. Birth weight was not associated with the metabolic syndrome (odds ratio OR = 0.67, 95% confidence interval CI = 0.25-1.79). Birth weight lower than the median increased the risk for having at least two components (OR = 2.28, 95% CI = 1.15-4.50). Subjects who smoked and had a birth weight lower than the median had a 6.9 times increased risk. Modification by lifestyle measured at age 36 was not observed, although effect modification using lifestyle data from 32 years was found. Lower birth weight increased the risk for having at least two components of the metabolic syndrome. Smoking, being less physical active or fit, have an unfavorable diet at age 32 adds to this risk.


Relationship between polymorphisms in the proline dehydrogenase gene and schizophrenia risk.
Previous studies have suggested that an association exists between the proline dehydrogenase gene (PRODH) and increased schizophrenia risk. We examined the prevalence of the PRODH 757C/T (Arg185Trp), 1766A/G (Gly521Arg), and 1852G/A (intronic mutation) polymorphisms in 175 patients with schizophrenia and 185 control subjects. All subjects were of Iranian ancestry. The PRODH 757TT, 1852AA, and 1766GG genotypes were associated with an increased risk of schizophrenia (odds ratio = 1.38, 95% confidence interval: 0.88-2.16, P = 0.001, P = 0.001, respectively). The activity alleles in the PRODH genotype combinations were associated with an increased risk of schizophrenia (haplotype analysis, TAG genotype P = 0.007). Our findings support a major role for the PRODH 757TT, 1766GG, and 1852AA genotypes alone and in combination for schizophrenia susceptibility.


Comparative stability-indicating chromatographic methods for determination of 4-hexylresorcinol in pharmaceutical formulation and shrimps.
Three chromatographic stability-indicating methods were developed for determination of 4-hexylresorcinol in pure form and in a pharmaceutical formulation. Method A was based on a gradient elution liquid chromatographic HPLC determination of 4-hexylresorcinol, its related impurities and in presence of its degradation products. UPLC-MS/MS (Method B) was described for determination of the cited drug in presence of its degradation products. Method C was a thin- layer chromatography (TLC)-densitometry method for the separation and determination of the active ingredient, one of its related impurities and in presence of its degradation products. The mechanism of alkali, oxidative and photodegradation of 4-hexylresorcinol was studied according to ICH guidelines. The degradation products were characterized by the LC-MS/MS method. Methods A and B were applicable for determination of 4-hexylresorcinol residues in shrimp meat. The studied drug was easily degraded in alkali medium giving toxic compounds. The results obtained by the proposed methods were statistically analyzed and compared with those obtained by applying a reported method.


Chinese herbal medicine for the treatment of prehypertension.
Objectives. To assess the current clinical evidence of Chinese herbal medicine (CHM) for prehypertension. Search Strategy. Electronic databases were searched until May, 2013. Inclusion Criteria. We included randomized clinical trials testing CHM against life style intervention and no treatment, or combined with life style intervention against life style intervention. Data Extraction and Analyses. Study selection, data extraction, quality assessment, and data analyses were conducted according to Cochrane standards. Results. Five trials were included. Methodological quality of the trials was evaluated as generally low. Only 1 trial reported allocation sequence. No trial reported the allocation concealment, double blinding, placebo control, presample size estimation, intention to treat analysis, and drop-out. All the included trials were not multicenter and large scale. Although meta-analysis showed that CHM is superior to either life style intervention group or no treatment group in decreasing blood pressure, we are unable to draw a definite conclusion on the effect of CHM due to the poor research methods used in the reviewed trials. The safety of CHM is still uncertain. Conclusions. There is no evidence to show that CHM is effective and safe for prehypertension due to serious methodological flaw of the reviewed trials. Rigorously designed trials are warranted to confirm these results.


Superresolution and pulse-chase imaging reveal the role of vesicle transport in polar growth of fungal cells.
Polarized growth of filamentous fungi requires continuous transport of biomolecules to the hyphal tip. To this end, construction materials are packaged in vesicles and transported by motor proteins along microtubules and actin filaments. We have studied these processes with quantitative superresolution localization microscopy of live Aspergillus nidulans cells expressing the photoconvertible protein mEosFPthermo fused to the chitin synthase ChsB. ChsB is mainly located at the Spitzenkörper near the hyphal tip and produces chitin, a key component of the cell wall. We have visualized the pulsatory dynamics of the Spitzenkörper, reflecting vesicle accumulation before exocytosis and their subsequent fusion with the apical plasma membrane. Furthermore, high-speed pulse-chase imaging after photoconversion of mEosFPthermo in a tightly focused spot revealed that ChsB is transported with two different speeds from the cell body to the hyphal tip and vice versa. Comparative analysis using motor protein deletion mutants allowed us to assign the fast movements (7 to 10 μm s-1) to transport of secretory vesicles by kinesin-1, and the slower ones (2 to 7 μm s-1) to transport by kinesin-3 on early endosomes. Our results show how motor proteins ensure the supply of vesicles to the hyphal tip, where temporally regulated exocytosis results in stepwise tip extension.


[Are the indications and choice of labile blood products adapted? National survey on prescriber's knowledge].
There is little data available on current practice related to prescription of labile blood products (LBP) by French physicians. The aim of this study was to assess whether prescriptions were conform to Anaes (French Medicine's agency) guidelines, with regard not only to indications but also quality of the products, so as to define the improvements that could be made. Thirty-four clinical case reports, classified by specialties were sent to prescribing physicians working in the regional health centers, from 17 different blood banks, from October 1997 to February 1998. The prescribers were requested to answer only the questions that were specific to their particular field of experience. Each case description included multiple choice questions on the indication for transfusion of concentrated of red blood cells (RBC) and/or platelets (CP) and/or plasma, and the possible requirements for specification or modification of the guidelines applicable to these products. The primary end point of analysis was the adequation of the answers to the Anaes recommendations. Answers were obtained regarding 5092 clinical cases from 818 physicians. The participation rate was of 30%. The specialties were as follows: 34% anesthesiologists, 14% oncologists-haematologists, 13% internal medicine specialists, 11% emergency physicians, 10% paediatricians, 8% obstetricians, 7% geriatricians, and 3% transplantation surgeons. Eighty-two percent of the answers came from physicians working in the public health services. The adequation with the indication for transfusion was of 90.3% for RBC, 92.3% for platelets and 93.8% for plasma. The percentages of correct answers regarding the indications for specification or modification of the LBP were as follows: 90.3% were correct for irradiation (of either RBC or platelets); 68.8% and 53.2% respectively for leukocyte depletion from RBC and platelets; 64% for phenotyped RBC; 68.2% for compatibilized RBC; and 57.3% for apheresis platelet concentrates. There was no difference in results depending on the type of center, private or public, and the quality of LBP prescribed. The answers obtained from the anaesthesiologists' clinical cases were less accurate with regard to RBC but more accurate with regard to PC compared with other specialists. This study shows the correct management of the indications for transfusion by the prescribing physicians who participated in the study, but the lack of knowledge with regard to the indications for specifications and/or transformations of LBP. The respect of the indications for transfusion is the corner stone of safe transfusion and this phase should be optimized with improved dissemination of information on transfusion and training for the physicians and programs that would improve the quality.


[Neutrophilic granulocytes in of the ovarian cancer progression].
The studies determining phagocytic activity, the levels of myeloperoxidase (MPO) and cationic proteins (CP), and the results of the spontaneous and induced NST tests of peripheral neutrophilic granulocytes (NGC) revealed their functional changes in the course of tumor progression in patients with ovarian cancer. There was an increase in the total count of NGC with simultaneous reductions in the levels of CP, the activity of MPO and in the absorptive capacity of NGC at the late clinical stages of the disease. The results of the NST test did not change. The findings suggest that a growing tumor affects NGC reproduction.