Muscle Activity Pattern Dysfunction During Sit to Stand and Stand to Sit in the Movement System Impairment Subgroups of Low Back Pain.
To investigate impairment in the activity pattern of some muscles involved in sit to stand (STD) and stand to sit (STS) among 2 low back pain (LBP) subgroups of the Movement System Impairment (MSI) model. Case-control study. A university medical center. Fifteen women without chronic LBP and 22 women with chronic LBP (N=37) in 2 subgroups (15 into the lumbar extension rotation (LER) and 7 into lumbar flexion rotation [LFR]) voluntarily participated in this study. Participants were asked to perform STD and STS at a preferred speed. Surface electromyography (EMG) were measured bilaterally from the internal oblique (IO), lumbar erector spine (ES), medial hamstring (MH), and lateral hamstring (LH) muscles. Changes in mean and maximum amplitude, time to peak amplitude, duration of muscle activity, and bilateral asymmetry of these variables. During STD, bilateral asymmetry in mean amplitude of MH in the LER subgroup (P=.031) and bilateral asymmetry in duration of LH in the LFR subgroup (P=.026) were exhibited. Also, in this task reduced time to peak left MH activation were found in the LFR subgroup than 2 other groups (control; P=.028/LER; P=.004). During STS, increased left ES maximum amplitude were observed in the LFR subgroup than LER subgroup (P=.029). Also, reduced time to peak right ES (P=.035) and left LH (P=.038) activation in the LER subgroup than control subjects and reduced time to peak left LH activation in LFR subgroup than control subjects (P=.041) were observed during STS. The differences between the 2 LBP subgroups may be a result of impairment in the activity pattern of some muscles during functional activity.


Monte Carlo simulations of a scintillation camera using GATE: validation and application modelling.
Geant4 application for tomographic emission (GATE) is a recently developed simulation platform based on Geant4, specifically designed for PET and SPECT studies. In this paper we present validation results of GATE based on the comparison of simulations against experimental data, acquired with a standard SPECT camera. The most important components of the scintillation camera were modelled. The photoelectric effect. Compton and Rayleigh scatter are included in the gamma transport process. Special attention was paid to the processes involved in the collimator: scatter, penetration and lead fluorescence. A LEHR and a MEGP collimator were modelled as closely as possible to their shape and dimensions. In the validation study, we compared the simulated and measured energy spectra of different isotopes: 99mTc, 22Na, 57Co and 67Ga. The sensitivity was evaluated by using sources at varying distances from the detector surface. Scatter component analysis was performed in different energy windows at different distances from the detector and for different attenuation geometries. Spatial resolution was evaluated using a 99mTc source at various distances. Overall results showed very good agreement between the acquisitions and the simulations. The clinical usefulness of GATE depends on its ability to use voxelized datasets. Therefore, a clinical extension was written so that digital patient data can be read in by the simulator as a source distribution or as an attenuating geometry. Following this validation we modelled two additional camera designs: the Beacon transmission device for attenuation correction and the Solstice scanner prototype with a rotating collimator. For the first setup a scatter analysis was performed and for the latter design. the simulated sensitivity results were compared against theoretical predictions. Both case studies demonstrated the flexibility and accuracy of GATE and exemplified its potential benefits in protocol optimization and in system design.


Current trend of pneumococcal serotypes distribution and antibiotic susceptibility pattern in Malaysian hospitals.
From January 2008 to December 2009, 433 Streptococcus pneumoniae strains were examined to determine the serotype distribution and susceptibility to selected antibiotics. About 50% of them were invasive isolates. The strains were isolated from patients of all age groups and 33.55% were isolated from children below 5 years. The majority was isolated from blood (48.53%) and other sterile specimens (6.30%). Community acquired pneumonia (41.70%) is the most common diagnosis followed by sepsis (9.54%). Serotyping was done using Pneumotest Plus-Kit and antibiotic susceptibility pattern was determined by modified Kirby-Bauer disk diffusion method and measurement of minimum inhibitory concentration (MIC) using E-test strip. Ten most common serotypes were 19F (15.02%), 6B (10.62%), 19A (6.93%), 14 (6.70%), 1 (5.08%), 6A (5.08%), 23F (4.85%), 18C (3.93%), 3 (2.08%) and 5 (1.85%). Penicillin MIC ranged between ≤ 0.012-4 μg/ml with MIC₉₀ of 1 μg/ml. Penicillin resistant rate is 31.78%. The majority of penicillin less-susceptible strains belonged to serotype 19F followed by 19A and 6B. Based on the serotypes distribution 22 (44.00%), 28 (56.00%) and 39 (78.00%) of the invasive isolates from children ≤ 2 years were belonged to serotypes included in the PCV7, PCV10 and PCV13, respectively.


Molecular design and preparation of bis-isophthalate electrochromic systems having controllable color and bistability.
New electrochromic systems based on bis-isophthalates were designed and prepared. They showed electrochromism behavior by two-electron reduction. The displayed colors showed greatly enhanced bistability and were dependent on the length of the conjugated bridge between the two isophthalate groups. We believe that the connection of two electrochromic systems with a conjugated bridge is a good basic strategy to obtain new bistable electrochromic systems.


Hepatic insulin gene therapy normalizes diurnal fluctuation of oxidative metabolism in diabetic BB/Wor rats.
Previous studies of hepatic insulin gene therapy (HIGT) focused on glycemic effects of insulin produced from hepatocytes. In this study, we extend the observations of glycemic control with metabolically regulated HIGT to include systemic responses and whole-body metabolism. An insulin transgene was administered with an adenoviral vector [Ad/(GlRE)(3)BP1-2xfur] to livers of BB/Wor rats made diabetic with polyinosinic polycytidilic acid (poly-I:C) (HIGT group), and results compared with nondiabetic controls (non-DM), and diabetic rats receiving different doses of continuous-release insulin implants (DM-low BG and DM-high BG). Blood glucose and growth normalized in HIGT, with lower systemic insulin levels, elevated glucagon, and increased heat production compared with non-DM. Minimal regulation of systemic insulin levels were observed with HIGT, yet the animals maintained normal switching from carbohydrate to lipid metabolism determined by respiratory quotients (RQs), and tolerated 24-hour fasts without severe hypoglycemia. HIGT did not restore serum lipids as we observed increased triglycerides (TGs) and increased free fatty acids, but reduced weight of visceral fat pads despite normal total body fat content and retroperitoneal fat depots. HIGT favorably affects blood glucose, normalizes metabolic switching in diabetic rats, and reduces intra-abdominal fat deposition.


Ligand exclusion on acetylcholinesterase.
This paper examines covalent reactivity of AchE with respect to cationic and uncharged methylphosphonates and substrates in the absence and presence of cationic ligands selective for the active center and the peripheral anionic site. The organophosphorus inhibitors are enantiomeric alkyl methylphosphonothioates (1-5) containing cycloheptyl and isopropyl phosphono ester groups and S-methyl, S-n-pentyl, and S-[beta-(trimethylammonio)ethyl] leaving groups; these agents differ in their configuration about phosphorus and their steric, hydrophobic, and electrostatic characteristics. The synthetic substrates examined are acetylthiocholine, p-nitrophenyl acetate, and 7-acetoxy-4-methylcoumarin (7AMC). Antagonism of the methylphosphonothioate reaction by cationic ligands is strongly dependent on the nature of both the cation and the methylphosphonate but independent of the configuration about phosphorus. While all cations cause linear mixed inhibition of acetylthiocholine hydrolysis, there are observed a variety of inhibition patterns of 7AMC and p-nitrophenyl acetate hydrolysis that are distinctly nonlinear, as well as patterns in which the reciprocal plots intersect in the upper right quadrant. Strong antagonism of cationic (methylphosphonyl)thiocholines correlates very well with linear inhibition of acetylthiocholine. Ligands that cause only negligible antagonism of the uncharged methylphosphonates display nonlinear inhibition of uncharged substrates. These relationships, since they are most pronounced for peripheral site ligands and are strongly dependent on the charge carried by the reactant, suggest that the peripheral anionic site alters enzyme reactivity through an electrostatic interaction with the net negative active center. Such behavior indicates a potential role for the peripheral anionic site in conserving AchE catalytic efficiency within a narrow range of values.


Motor neurons and motor columns of the anterior spinal cord of salamanders: posthatching development and phylogenetic distribution.
The posthatching development of rostral (1st-4th) spinal motor neurons was studied in ten species of salamanders, using horseradish peroxidase and cobaltic lysine tracing techniques. Development of spinal motor neurons differs among species in association with differences in life history and general developmental patterns (i.e., between species with aquatic larvae versus those with direct development, with or without ontogenetic repatterning). In the plesiomorphic state, represented by species with aquatic larvae, five types of motor neurons are present: (1) large, multipolar neurons, believed to be primary motor neurons; (2) medial, pear-shaped neurons; (3) larger, spindle-shaped neurons, which increase in number during posthatching development; (4) cone-shaped neurons, and (5) bilaterally arborizing neurons (found only at the rostral pole of the first spinal nucleus). Direct-developing desmognathine salamanders have the plesiomorphic set of motor neurons, but appear to lack Mauthner neurons. Direct-developing plethodontine salamanders have cone-shaped, pear-shaped, and spindle-shaped neurons, but lack primary motor neurons and Mauthner neurons. Direct-developing bolitoglossine salamanders, which exhibit both pedomorphosis and ontogenetic repatterning, have only medial, pear-shaped neurons, and lack primary motor neurons, spindle-shaped neurons, cone-shaped and bilaterally arborizing neurons. At all developmental stages in all species studied, pear-shaped neurons are always found in medial positions and spindle-shaped neurons are always found in lateral positions. Spindle-shaped neurons are found more laterally as development proceeds. The medial and lateral motor columns of salamanders and amniotes differ in their connections with peripheral targets (i.e., axial muscles vs. limbs). This implies a lack of homology of neuron types in salamanders and amniotes, which has been obscured by the current terminology.


Oxidative stress on land snail Helix aspersa as a sentinel organism for ecotoxicological effects of urban pollution with heavy metals.
The oxidative stress in the digestive gland of the land snail Helix aspersa was considered as a bioindicator for atmospheric pollution with heavy metals from several industries and vehicular traffic in Kafr El-Zayat city. Regional means of heavy metals concentration of all sites were 0.71, 7.09, 0.71, 2.68, 41.44 and 18.01 mg kg(-1) wet mass for Cd, Mn, Ni, Pb, Zn and Cu, respectively. In addition, the highest values of Cd concentrations were found 1.22 and 1.73 mg kg(-1) wet mass in S1 (Potato International Center) and S4 (The Nile bank), respectively. Lactate dehydrogenase (D-LDH(and recorded lipid peroxidation (LPO) levels were significantly high in S1 and S2 (Traffic station). On the other hand, the highest activity of catalase (CAT) was found in S2 (194.04% of control), while the activity of glutathione peroxidase (GPx) reached the highest significant value in S1. As a matter of fact, glutathione-S-transferase (GST) and glutathione reductase (GR) activities were significantly higher in polluted sites than in reference zone. In contrast, the glutathione (GSH) concentration of exposed animals showed significant decrease in all sites, with the lowest value in S1 (57.61% of control). However, metallothioneins concentration (MT) showed no significant difference in all sites except in S1 which accounted for 127.81% of control. Therefore, the overall results of this study showed the importance of H. aspersa as a sentinel organism for biomonitoring the biologic impact of atmospheric pollution in urban areas.


Identification of diacetylmorphine metabolites in humans.
With the techniques of column chromatography, TLC, and GLC, morphine, 6-acetylmorphine, normorphine, morphine 3-glucuronide, 6-acetylmorphine 3-glucuronide, and normorphine glucuronide were identified as metabolites of diacetylmorphine (heroin) in the urine of humans administered 10 mg iv/70 kg body weight.


Immunohistochemical detection of proliferating tumor cells in cervical cancer using monoclonal antibody Ki-67.
Monoclonal antibody Ki-67 identifies cells in G1, S, G2, and M phases of the cell cycle. In this cytokinetic study, Ki-67 was used to characterize tumor cells in human cervical cancer specimen. This immunohistochemical study showed that Ki-67 staining gave a brown nuclear reactivity dispersed heterogeneously in a tumor cell population and correlated well with the mitotic activities of tumor cells. The finding suggested that Ki-67 staining provides an easily countable index for the study of proliferating cell populations in cervical cancer.


Acute appendicitis after diaphragmatic hernia after pediatric liver transplant.
Multiple complications in liver transplant have been described in the literature. However, appendicitis and diaphragmatic hernia have rarely been reported after solid-organ transplant. The clinical presentation of appendicitis is similar to that of nontransplant patients, but complications are more frequent, because the majority of the patients do not have leukocytosis. Diaphragmatic hernia can present with a variety of atypical clinical symptoms. In this report, 1 patient who developed a diaphragmatic hernia and appendicitis after liver transplant is presented. A 2-year-old boy with end-stage liver cirrhosis owing to progressive familial intrahepatic cholestasis type-2 received a living-donor liver transplant. The posttransplant course was complicated. The diagnosis of diaphragmatic hernia was confirmed by thoracoabdominal computed tomography, and we decided to proceed with surgical repair. The patient had evidence of perforation, and the appendix was removed. After repositioning the intestine in the abdomen, a chest tube was placed, and the defect repaired with interrupted polypropylene sutures. The patient recovered after surgery without untoward sequelae.


Valley density profile for highly efficient x-ray lasers with good beam quality.
A plasma with a valley density profile at the required electron density for high-gain operation of an x-ray laser could be obtained using a normally incident 300 ps laser pulse followed by a grazing-incident 300 ps laser pulse. Sudden heating of the valley plasma region by another grazing-incident 300 fs laser pulse would then yield a highly efficient x-ray laser beam with a deflecting angle of 2 mrad and a divergence angle of 4 mrad. Saturation operation of the x-ray laser beam at 32.6 nm could be achieved with a total pump energy of less than 100 mJ.


Adenosine as a Multi-Signalling Guardian Angel in Human Diseases: When, Where and How Does it Exert its Protective Effects?
The importance of adenosine for human health cannot be overstated. Indeed, this ubiquitous nucleoside is an integral component of ATP, and regulates the function of every tissue and organ in the body. Acting via receptor-dependent and -independent mechanisms [the former mediated via four G-protein-coupled receptors (GPCRs), A1, A2A, A2B, and A3,], it has a significant role in protecting against cell damage in areas of increased tissue metabolism, and combating organ dysfunction in numerous pathological states. Accordingly, raised levels of adenosine have been demonstrated in epilepsy, ischaemia, pain, inflammation, and cancer, in which its behaviour can be likened to that of a guardian angel, even though there are instances in which overproduction of adenosine is pathological. In this review, we condense the current body of knowledge on the issue, highlighting when, where, and how adenosine exerts its protective effects in both the brain and the periphery.


Intersecting Health Policy and the Social Determinants of Health in Pediatric Type 1 Diabetes Management and Care.
Type 1 diabetes health technologies are evolving. This is an expensive chronic condition to manage, hence a combination of public and private healthcare funding sources, as well as out-of-pocket payments support disease management. The aim of this paper is to describe two conceptual underpinnings, which can appropriately position the health policy and clinical context of pediatric type 1 diabetes management and care. PHENOMENA ADDRESSED: "The Main Determinants of Health" framework is used to position pediatric T1D management and care within the model's four interconnected layers: the structural environment, social and material conditions, support systems and individual health behaviors. A health policy in Ontario, Canada, the Assistive Devices Program for insulin pump therapy is also discussed relative to the model's outermost layer: the structural environment. Four dimensions of control, which characterize the "street-level bureaucrat" role including "distributing benefits and sanctions; structuring the context; teaching the client role; and, psychological benefits and sanctions" then position the policy context of the diabetes nurse educator role relative to the Assistive Devices Program policy. These conceptual underpinnings could extend beyond the pediatric T1D landscape to position global research in other nursing practice areas, as well as with other patient populations and professional disciplines such as social work and medicine.


Application of diffusion kurtosis imaging to odontogenic lesions: Analysis of the cystic component.
To assess the feasibility of applying diffusion kurtosis imaging (DKI) to common odontogenic lesions and to compare its diagnostic ability versus that of the apparent diffusion coefficient (ADC) for differentiating keratocystic odontogenic tumors (KCOTs) from odontogenic cysts. Altogether, 35 odontogenic lesions were studied: 24 odontogenic cysts, six KCOTs, and five ameloblastomas. The diffusion coefficient (D) and excessive kurtosis (K) were obtained from diffusion-weighted images at b-values of 0, 500, 1000, and 1500 s/mm2 on 3T magnetic resonance imaging (MRI). The combination of D and K values showing the maximum density of the probable density function was estimated. The ADC was obtained (0 and 1000 s/mm2 ). Values for odontogenic cysts, KCOTs, and ameloblastomas were compared. Multivariate logistic regression modeling was performed to assess the combination of D and K model versus ADC for differentiating KCOTs from odontogenic cysts. The mean D and ADC were significantly higher for ameloblastomas than for odontogenic cysts or KCOTs (P < 0.05). The mean K was significantly lower for ameloblastomas than for odontogenic cysts or KCOTs (P < 0.05). The mean values of all parameters for odontogenic cysts and KCOTs showed no significant differences (P = 0.369 for ADC, 0.133 for D, and 0.874 for K). The accuracy of the combination of D and K model (76.7%) was superior to that of ADC (66.7%). Use of DKI may be feasible for common odontogenic lesions. A combination of DKI parameters can be expected to increase the accuracy of its diagnostic ability compared with ADC. J. Magn. Reson. Imaging 2016;44:1565-1571.


Controlled Folding of Single Crystal Graphene.
Folded graphene in which two layers are stacked with a twist angle between them has been predicted to exhibit unique electronic, thermal, and magnetic properties. We report the folding of a single crystal monolayer graphene film grown on a Cu(111) substrate by using a tailored substrate having a hydrophobic region and a hydrophilic region. Controlled film delamination from the hydrophilic region was used to prepare macroscopic folded graphene with good uniformity on the millimeter scale. This process was used to create many folded sheets each with a defined twist angle between the two sheets. By identifying the original lattice orientation of the monolayer graphene on Cu foil, or establishing the relation between the fold angle and twist angle, this folding technique allows for the preparation of twisted bilayer graphene films with defined stacking orientations and may also be extended to create folded structures of other two-dimensional nanomaterials.


Delay in the Diagnosis of APECED: A Case Report and Review of Literature from Iran.
Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) syndrome is a rare monogenic autosomal recessive disorder caused by biallelic mutations in the AIRE (autoimmune regulator) gene. Patients with APECED present with heterogeneous endocrine and non-endocrine manifestations. In this study, we report an Iranian patient who presented with Addison disease, chronic mucocutaneous candidiasis, alopecia totalis, keratopathy and asplenia treated as an isolated endocrinopathy for 25 years. In the adulthood, the diagnosis of APECED was made by genetic analysis which demonstrated homozygous nonsense p.R257* (c.769C>T) mutation of AIRE. APECED has been shown to be frequent in some ethnicities including Iranian Jews. Therefore, we reviewed 39 Iranian APECED patients published in the literature. We found that most of the Iranian patients were of Jewish ethnic background and presented hypoparathyroidism, adrenal insufficiency, and candidiasis as the main clinical manifestation.


Intestinal absorption of lysozyme, an egg-white allergen, in rats: kinetics and effect of NSAIDs.
The absorption pathway(s) of a representative food allergen, lysozyme, and the mechanisms of lysozyme absorption facilitated by non-steroidal anti-inflammatory drugs were examined by intestinal closed-loop and re-circulating perfusion methods in rats. The absorption rate of fluorescein isothiocyanate (FITC)-labeled lysozyme in the proximal intestine was higher than that for a marker of non-specific absorption, FD-10, and was suppressed by colchicine (endocytosis inhibitor). Aspirin increased the absorption of FITC-lysozyme in the proximal intestine with no effects on tissue accumulation. Diclofenac facilitated FITC-lysozyme absorption, but meloxicam and loxoprofen exerted no effects on absorption. Co-administration of misoprostol (synthetic prostaglandin-E1 analog) with aspirin significantly ameliorated the aspirin-facilitated absorption of FITC-lysozyme to the same level as that seen with controls. Thus, lysozyme absorption was mediated by endocytic and paracellular pathways in the proximal intestine, and was facilitated by aspirin and diclofenac after impairment of the paracellular pathway. Misoprostol may suppress the allergen absorption facilitated by aspirin.


An improved and simplified method for combined light and scanning electron microscopy in human urinary cytology.
Human bladder-washing and voided urine specimens from normal cases and inflammatory and malignant lesions were examined by the combined use of light microscopy (LM) and scanning electron microscopy (SEM). A newly-designed mesh, which consisted of a piece of gelatin-covered, osmium-impregnated and poly-L-lysine-coated glass slide, 0.85 mm in thickness and containing 42 compartments of 25 sq mm in size, was used in this study. This mesh permitted a direct correlation of LM and SEM images, thus shortening the time of observation of specimens under SEM. With SEM, the diagnosis of malignant exfoliated urothelial cells depended on the presence or absence of pleomorphic microvilli. The technique has enhanced the accuracy of diagnosis over conventional methods, especially for noninvasive, low-grade, papillary tumors of the urinary bladder.


Oxidative stress intensity-related effects of cadmium (Cd) and paraquat (PQ) on UV-damaged-DNA binding and excision repair activities in zebrafish (Danio rerio) embryos.
Our earlier studies showed the inhibitory effects of cadmium (Cd) and paraquat (PQ) on the gene expression of DNA mismatch recognition proteins in zebrafish (Danio rerio) embryos. This study explored the effects of Cd and PQ on nucleotide excision repair (NER) capacity in zebrafish embryos. Exposure of embryos at 1 h post fertilization (hpf) to 3-5 μM Cd or 30-100 μM PQ for 9 h induced a 2-3-fold increase of oxidative stress, while a 6.5-fold increase of oxidative stress was induced by 200 μM PQ. Real-time RT-PCR detected a down-regulated xeroderma pigmentosum C (XPC) and an up-regulated UV-DDB2 gene expression in mildly-stressed embryos, whereas 8-oxoguanine DNA glycosylase (OGG1) gene expression increased with PQ exposure levels. NER of UV-damaged DNA was enhanced in weakly oxidant-stressed embryos as shown by a transcription-based DNA repair assay, yet repair activities of both UV and cisplatin-damaged DNA were inhibited in embryos exposed to 200 μM PQ. Band shift assay showed a suppression of cyclobutane pyrimidine dimer (CPD) binding activity in all stressed embryos. In contrast, (6-4) photoproduct (6-4PP) recognition activity was weakly stimulated except in embryos exposed to 200 μM PQ, revealing a link of NER capacity to 6-4PP binding. Our results showed that Cd and PQ imposed similar inducing effects on UV-DDB2 gene expression, NER of UV-damaged DNA and 6-4PP binding activity in zebrafish embryo under low levels of oxidative stress and NER capacity could be inhibited if the intensity of oxidative stress increased to a critical level.


Diffuse ulcerations due to disseminated histoplasmosis in a patient with HIV.
Disseminated histoplasmosis is a serious disease that affects the skin, lungs, and internal organs. It is one of the diseases that characterize acquired immunodeficiency syndrome (AIDS), and in endemic areas is one of the more commonly observed infections in AIDS patients. The mortality rate in patients with AIDS and histoplasmosis is high if untreated. Disseminated histoplasmosis may have a variety of dermatological manifestations. In this article, we provide the first report of diffuse ulcerations due to disseminated histoplasmosis. These ulcers developed while the patient was on stavudine, lamivudine, and indinavir, and had a CD-4 count of 525 mm3. The patient's histoplasmosis resolved with itraconazole monotherapy. Histoplasmosis is a well-described opportunistic infection that accompanies human-immunodeficiency virus (HIV) infection. We report an unlikely victim of disseminated histoplasmosis who suffered this infection while on antiretroviral therapy and with a CD-4 count of 525/mm3. Notably, he had a normal chest x-ray and disseminated cutaneous ulcers. The diagnosis was made by skin biopsy, and his infection responded promptly to itraconazole therapy. This case serves as a reminder that the immunological derangements and cutaneous alterations wrought by HIV remain unpredictable in nature and extent.


Individuals with Alzheimer's learn to play a tile placement game: Results of a pilot study: Innovative practice.
With the ongoing need to determine effective memory interventions for persons with dementia and other memory impairments, the purpose of this study was to create a unique learning opportunity, where persons with early to moderate Alzheimer's engaged in game play activity. Six female participants, diagnosed with early to moderate dementia, were recruited from an adult day care center and participated in a 10-week study. The participants were placed in groups of three and were taught a tile placement game. Results indicate playing the game yielded inconsistent, but some significant, increases and eventual plateauing of knowing when it was their turn. The results also indicate the participant's maintained improvement in tile placement over the study period. Tile placement accuracy increased over rounds, which points to the importance of practice to maintain learned behavior. The game provided a platform for learning, social engagement, and occupied their time meaningfully.


Pediatric hereditary autoinflammatory syndromes.
To describe the most prevalent pediatric hereditary autoinflammatory syndromes. A review of the literature including relevant references from the PubMed and SciELO was carried out using the keywords autoinflammatory syndromes and child. The hereditary autoinflammatory syndromes are caused by monogenic defects of innate immunity and are classified as primary immunodeficiencies. These syndromes are characterized by recurrent or persistent systemic inflammatory symptoms and must be distinguished from infectious diseases, autoimmune diseases, and other primary immunodeficiencies. This review describes the epidemiological, clinical and laboratory features, prognosis, and treatment of the main autoinflammatory syndromes, namely: familial Mediterranean fever; TNF receptor associated periodic syndrome; the cryopyrinopathies; mevalonate kinase deficiency; pediatric granulomatous arthritis; pyogenic arthritis, pyoderma gangrenosum and acne syndrome; Majeed syndrome; and deficiency of interleukin 1 receptor antagonist. The cryopyrinopathies discussed include neonatal-onset multisystem inflammatory disease (also known as chronic infantile neurologic, cutaneous and articular syndrome), Muckle-Wells syndrome, and familial cold autoinflammatory syndrome. Pediatricians must recognize the clinical features of the most prevalent autoinflammatory syndromes. Early referral to a pediatric rheumatologist may allow early diagnosis and institution of treatment, with improvement in the quality of life of these patients.


Adverse childhood experiences, self-care, and compassion outcomes in mental health providers working with trauma.
This study examined the moderating effects of self-care on various compassion outcomes among mental health providers. Mental health providers (n = 371; 94.1% female; mean age = 47.12) were surveyed regarding their level of self-care, history of adverse childhood experiences, and the degree of burnout, secondary traumatic stress, and compassion satisfaction experienced. Results indicated that providers who endorsed a history of adverse childhood experiences (82.5%) also endorsed greater negative compassion outcomes than those who did not have such a history. Endorsement of self-care activities was a significant predictor of compassion satisfaction and burnout in the expected directions. Self-care served as a moderator between adverse childhood experiences and burnout. Self-care is an effective method for decreasing negative compassion outcomes among mental health providers who work with trauma. It is important to develop effective training programs that promote self-care in personal and professional settings.


Arachnia propionica pneumonia in hairy cell leukaemia.
Pulmonary infection caused by Arachnia propionica in a patient with hairy cell leukaemia is described. The organism is highly sensitive to penicillin but the patient succumbed to his illness despite treatment with penicillin and various other antibiotics. Various types of opportunist infections are common in patients with hairy cell leukaemia but we believe this to be the first report of infection by Arachnia propionica in such a patient.


Direct medical mental health care costs of schizophrenia in France, Germany and the United Kingdom - findings from the European Schizophrenia Cohort (EuroSC).
To quantify and compare the resource consumption and direct costs of medical mental health care of patients suffering from schizophrenia in France, Germany and the United Kingdom. In the European Cohort Study of Schizophrenia, a naturalistic two-year follow-up study, patients were recruited in France (N=288), Germany (N=618), and the United Kingdom (N=302). Data about the use of services and medication were collected. Unit cost data were obtained and transformed into United States Dollar Purchasing Power Parities (USD-PPP). Mean service use and costs were estimated using between-effects regression models. In the French/German/UK sample estimated means for a six-month period were respectively 5.7, 7.5 and 6.4 inpatient days, and 11.0, 1.3, and 0.7 day-clinic days. After controlling for age, sex, number of former hospitalizations and psychopathology (CGI score), mean costs were 3700/2815/3352 USD-PPP. Service use and estimated costs varied considerably between countries. The greatest differences were related to day-clinic use. The use of services was not consistently higher in one country than in the others. Estimated costs did not necessarily reflect the quantity of service use, since unit costs for individual types of service varied considerably between countries.


Inhibitors of proteases and amide hydrolases that employ an alpha-ketoheterocycle as a key enabling functionality.
This article reviews the scientific literature on the application of alpha-ketoheterocycles to the discovery of potent enzyme inhibitors. The alpha-ketoheterocycle functionality provides a moderately electrophilic ketone carbonyl with 'tunable' reactivity, as well as a structural template for introducing new interactions in the enzyme active-site cleft. This type of moiety has served an important role in the design of active-site-directed inhibitors of diverse serine and cysteine proteases, and of fatty acid amide hydrolase (FAAH). Potent inhibitors have been identified for, inter alia, elastase, thrombin, factor Xa, tryptase, chymase, cathepsin K, cathepsin S, and FAAH. For example, 6e is an orally active inhibitor of human neutrophil elastase that entered human clinical studies, 52h is an orally bioavailable inhibitor of human chymase, and 82m is a FAAH inhibitor with in vivo endocannabinoid-enhancing activity.


B-cell subsets and the mature preimmune repertoire. Marginal zone and B1 B cells as part of a "natural immune memory".
The rate of elimination of a pathogenic agent is of critical importance for the host and determines the extent and consequences of the infection. Antibody production, along with the activity of other cells of the immune system, plays an important role early and late in the response and contributes to all containment and elimination of the organism. B-cell clones reaching the mature long-lived pool are heterogeneous: some belong to the B1 B-cell subset, some are enriched in the CD21high compartment (mostly marginal zone (MZ)), whereas others recirculate primarily among the B-cell follicles (FO). This segregation is a T-independent, CD40L-independent but BCR/CD19-dependent process. Antigen encounter will recruit antigen-specific cells from the pool of mature B-lymphocytes and activate them to perform effector functions. CD21highCD23low B cells enriched in the MZ of the spleen initiate the early plasmablast wave during the first 3 days of an antibody response against particulate T-independent bacterial antigens. These findings indicate a functional heterogeneity within the mature B-lymphocyte population. MZ B cells and B1 B, in contrast to FO B cells, have the unique capacity to generate effector cells in early stages of the immune response against (particulate) antigens that are scavenged efficiently in these specialized anatomical sites.


Application of Zinpyr-1 for the investigation of zinc signals in Escherichia coli.
Changes of the pico- to nanomolar concentration of free intracellular Zn(2+) are part of the signal transduction in mammalian cells. These zinc signals regulate the enzymatic activity of target proteins such as protein tyrosine phosphatases. For Escherichia coli, previous studies have reported diverging concentrations from femto- to picomolar, raising the question if Zn(2+) could also have a function in bacterial signaling. This manuscript explores the use of the low molecular weight fluorescent probe Zinpyr-1 in E. coli. The probe detects free Zn(2+) in these bacteria. Comparable to mammalian cells, other metal ions, especially Hg(2+) and Cd(2+), interfere with the detection of Zn(2+). Moreover, experiments in E. coli were particularly prone to artifacts based on cellular autofluorescence, necessitating corrections that are not required in mammalian cells. Based on measurements in lysates of E. coli and the mammalian cell line Jurkat, similar values between 0.1 and 0.2 nM free Zn(2+) were found. For E. coli, this corresponds to less than one free zinc ion per cell. Moreover, phosphatase inhibition by Zn(2+) was only observed in Jurkat, but not E. coli. This excludes a function for zinc signals as a regulator of bacterial phosphatases. Still, changes in the free Zn(2+) concentration were observed in response to elevated extracellular Zn(2+) and pH, or to addition of the detergent NP-40, suggesting that other processes could be controlled by the free intracellular Zn(2+) concentration.


Shrinking the Supply Chain for Implantable Coronary Stent Devices.
Stenting treatments for the management of disease in the heart, arterial and venous systems, biliary ducts, urethras, ureters, oesophageal tract and prostate have made enormous technical advances since their introduction into clinical use. The progression from metallic to polymer based bio-absorbable stents, coupled with the advances in additive manufacturing techniques, present a unique opportunity to completely re-envision the design, manufacture, and supply chain of stents. This paper looks at current stenting trends and proposes a future where the stent supply chain is condensed from ~150 days to ~20 min. The Cardiologist therefore has the opportunity to become a designer, manufacturer and user with patients receiving custom stents specific to their unique pathology that will be generated, delivered and deployed in the Cath-lab. The paper will outline this potentially revolutionary development and consider the technical challenges that will need to be overcome in order to achieve these ambitious goals. A high level overview of the generating eluting stents in situ program-GENESIS-is outlined including some early experimental work.


Carbonic anhydrase IX (CAIX) is not an independent predictor of outcome in patients with clear cell renal cell carcinoma (ccRCC) after long-term follow-up.
To evaluate carbonic anhydrase IX (CAIX) expression as an independent prognostic marker for clear cell renal cell carcinoma (ccRCC). With recent smaller studies showing conflicting results, we aimed to update our initial analysis in 2007 with an additional 5-year follow-up. We provided long-term follow-up of the same cohort used in our 2007 study (730 patients with unilateral, sporadic ccRCC treated surgically between 1990 and 1999). Associations of CAIX expression with RCC death and distant metastases were evaluated using Cox proportional hazards regression models. CAIX was expressed in 708 (97.0%) of the specimens; 163 tumours (22.3%) had low (≤85%) expression and 567 (77.7%) high (>85%) expression. There were 483 deaths and 265 RCC-specific deaths. The median follow-up for the 247 patients still under observation was 13.8 years. Univariately, low CAIX expression was associated with an increased risk of RCC death vs high expression (hazard ratio 1.62; P < 0.001). Low CAIX expression was not statistically significantly associated with RCC death or distant metastases after adjusting for nuclear grade or coagulative tumour necrosis. After additional long-term follow-up of our large cohort, our results continue to suggest that CAIX is not an independent prognostic marker for ccRCC.


Standardization of a preparative ultracentrifuge method for quantitative determination or protein binding of seven antibiotics.
A preparative ultracentrifuge method was standardized for determination of quantitative binding of cephalothin, cefamandole, cefazolin, cefaclor, erythromycin, gentamicin, and chloramphenicol to human serum proteins. At achievable in vivo concentrations, serum binding was 78.5% for cephalothin, 79.9% for cefamandole, 88.5% for cefazolin, 23.5% for cefaclor, 41.9% for erythromycin, 22.7% for gentamicin, and 59.5% for chloramphenicol. Techniques that use semipermeable cellophane or diaflow membranes, cross-linked dextran, inhibition of bacterial growth, protein precipitation, or liquid partitioning all have inherent problems with either the ligand or the antibiotic adversely interacting with the experimental apparatus. Ultracentrifugation provides a rapid, reproducible technique for protein-binding determinations of the classes of antibiotics described.


Banting Lecture: glucose turnover. A key to understanding the pathogenesis of diabetes (indirect effects of insulin).
This article is divided into two parts. A retrospective overview summarizes some of the work that provided the framework and tools of the more recent studies. The five novel areas of research are related to the indirect effects of insulin. Regulation of plasma glucose is of central importance in health and diabetes. Understanding this precise regulation requires sensitive isotope dilution methods that can measure the rates at which glucose is produced by the liver and used by the tissues on a minute-to-minute basis. Validation studies indicated that the non-steady-state tracer method yields reasonable results when the specific activity of plasma glucose does not change abruptly. During hyperinsulinemic glucose clamps, the decrease in specific activity of glucose can be prevented by the MSTI. During exercise, the decrease of specific activity can be only in part ameliorated by step-tracer infusion. Depancreatized dogs are used extensively as a model of selective insulin deficiency, because dog stomach secretes physiological amounts of glucagon. This strategy can avoid injections of somatostatin, which can have other affects in addition to the suppression of insulin and glucagon. In human diabetes, in addition to an increase of glucose production, there is also an increase in glucose cycling in the liver. In animal models of diabetes, mild NIDDM, and in glucose intolerance, the percentage of increments of glucose cycling are much larger than those of glucose production. We hypothesize, therefore, that measurements of glucose cycling can be used as an early marker of glucose intolerance. Application of different tracer strategies and use of the depancreatized dog as a model of diabetes, we investigated the importance of the indirect effects of insulin in the pathogenesis of diabetes. 1) Because, in the treatment of IDDM, insulin is administered by the peripheral routes we compared the relative importance of hepatic and peripheral effects of insulin in regulating the rate of glucose production. Experiments were performed in depancreatized dogs that were initially maintained at moderate hyperglycemia (10 mM) with subbasal portal insulin infusion. During the experimental period, insulin was infused either peripherally or portally at 0.9 mU.kg-1.min-1. In addition, peripheral infusions were also given at 0.45 mU.kg-1.min-1. We concluded that when suprabasal insulin levels are provided to moderately hyperglycemic depancreatized dogs, the suppression of glucose production is more dependent on peripheral than portal insulin concentrations. This indirect effect of insulin may be mediated by limitation of the flow of precursors and energy substrates for gluconeogenesis and/or by suppressive effect of insulin on glucagon secretion.(ABSTRACT TRUNCATED AT 400 WORDS)


Health status of the Neolithic population of Alepotrypa Cave, Greece.
During the Neolithic, human health and lifestyle changed following the adoption of domesticated plants and animals and sedentism. This paper presents a study on human osteological remains from Alepotrypa Cave, an important and very well-preserved Late and Final Greek Neolithic site occupied from 5000-3200 BC. The Alepotrypa sample comes from primary and secondary burials as well as scattered bone, and consists of a minimum number of 161 individuals. It includes equal proportions of adults and subadults and males and females, is characterized by high child mortality, and falls within the range of other Neolithic sites in terms of age profiles and stature. The most frequent pathological conditions observed in this population are: 1) anemic conditions (cribra orbitalia and porotic hyperostosis), mild or healed in manifestation, most probably of nutritional origin, resulting from a poor diet focused on terrestrial resources such as domesticated cereals; 2) osteoarthritis and musculoskeletal stress markers, indicative of increased physical activity and heavy workloads; and 3) elevated prevalence of healed, depressed cranial fractures, serving as evidence of violent, nonlethal confrontations. Teeth exhibit a low prevalence of dental carries and linear enamel hypoplasia. The overall demographic, pathological, and behavioral results are consistent with observations of Neolithic populations elsewhere in Greece and the Mediterranean.


[Professionalism of physicians from the point of view of physicians and students].
Professionalism should be included as a fundamental component in the curriculum of undergraduate as well as graduate students of Medicine. Future physicians should be aware of the attributes that a professional should possess. To analyze the ideal medical doctor attributes from the point of view of physicians and students of Medicine. One hundred four physicians (MD) and 47 students answered a free association test on the attributes they would assign to a good physician. The test was applied via Internet to professionals, and students were tested in group dynamics at the beginning of the class on Bioethics and Professionalism. Data were processed according to the Lexical Availability Model (LAM) which provides quantitative as well as qualitative evaluations. The attributes with higher scores among MD's were honesty (0.379), regular academic updating (0.373), ability (0.325) and empathy (0.241). Among students, the selected attributes were excellence (0.625), empathy (0.511), responsibility (0.280) and ability (0.209). A general agreement was found among physicians and students, excepts by the fact that MD's consider continuing academic updating as the most important attribute. The attributes that physicians and medical students evaluate as essential in professionalism were identified using the LAM approach. At the beginning of the career, students have a definite humanistic approach to their future profession.


Laboratory experiments for inter-comparison of three volume scattering meters to measure angular scattering properties of hydrosols.
Measurements of the volume scattering function (VSF) of hydrosols is of primary importance to investigate the interaction of light with hydrosols and to further interpret in situ and remote sensing data of ocean color. In this paper, a laboratory inter-comparison experiment of three recently developed VSF meters that are able to measure the scattered light for a wide range of scattering angle at 515 nm wavelength is performed using phytoplankton cultures and mineral-like hydrosols. A rigorous measurement protocol was employed to ensure good quality data. In particular, the protocol enabled removing the influence of bacteria on the hydrosols within the sample. The differences in the VSF measurements between the instruments vary from 10 to 25% depending on the composition of the hydrosols. The analysis of the angular features of the VSF revealed a sharp increase of the VSF beyond the scattering angle of 150° for some phytoplankton species. Such behavior is observed for two of the three VSF meters, thus suggesting that it is not due to instrumental artifacts but more likely to phytoplankton optical properties themselves. Moreover, comparisons with currently used theoretical phase functions show that the models are not able to reproduce satisfactorily the directional patterns in the backscattering region. This study suggests that a better modelling of the VSF shape of phytoplankton at high scattering angles is required to correctly represent the angular shape of the VSF in the backscattering hemisphere. Tabulated values of the measured phase functions are provided for scattering angles from 0.1 to 175°.


[Metabolism of glycolipids in the rat brain during acute and chronic ethanol administration].
Increase in content of sulfatides I and II and a decrease in cerebrosides was found in brain of rats after acute alcoholization with 25% ethanol, 4 g/kg, intragastric administration. In this case incorporation of 1,2-14C-ethanol into cerebrosides II and III was decreased. Content of sulfatides I was increased, while specific radioactivity of cerebrosides III--decreased as a result of chronic alcohol intoxication (25% ethanol, intragastric administration, 7 g/kg daily within 21 days).


[Impact of aortic stiffness on central hemodynamics and cardiovascular system].
Arterial stiffness increases as a result of degenerative processes accelerated by aging and many risk factors, namely arterial hypertension. Basic clinical examination reveals increased pulse pressure as its hemodynamic manifestation. The most serious consequence of increased vascular stiffness, which cannot be revealed by clinical examination, is a change of central hemodynamics leading to increased load of left ventricle, left ventricular hypertrophy, diastolic dysfunction and to overall increase of cardiovascular risk. This review aimed to point at some patophysiological mechanisms taking part in the development of vascular stiffness, vascular remodeling and hemodynamic consequences of these changes. This work also gives an overview of noninvasive examination methods and their characteristics enabling to evaluate the local, regional and systemic arterial stiffness and central pulse wave analysis and their meaning for central hemodynamics and heart workload.


Protein structure prediction and structural genomics.
Genome sequencing projects are producing linear amino acid sequences, but full understanding of the biological role of these proteins will require knowledge of their structure and function. Although experimental structure determination methods are providing high-resolution structure information about a subset of the proteins, computational structure prediction methods will provide valuable information for the large fraction of sequences whose structures will not be determined experimentally. The first class of protein structure prediction methods, including threading and comparative modeling, rely on detectable similarity spanning most of the modeled sequence and at least one known structure. The second class of methods, de novo or ab initio methods, predict the structure from sequence alone, without relying on similarity at the fold level between the modeled sequence and any of the known structures. In this Viewpoint, we begin by describing the essential features of the methods, the accuracy of the models, and their application to the prediction and understanding of protein function, both for single proteins and on the scale of whole genomes. We then discuss the important role that protein structure prediction methods play in the growing worldwide effort in structural genomics.


[An epidemiological survey of Clonorchiasis sinensis of 17 counties/cities of Hubei Province Research Institute for Parasitic Diseases].
An epidemiological survey was made on Clonorchiasis sinensis for the first time in 17 counties/cities of Hubei Province in 1988. The pathogen of clonorchiasis sinensis was found in 14 of the 17 counties/cities. Individual examination of some population was carried out and in 7 counties/cities, all the people were found to be infected. The infection rate was more than 10% in some of the places surveyed. Most of the cases were youngsters. The chief mode of infection was the habit of eating undercooked fish or holding fish in the mouth. These results showed that Clonorchiasis sinensis infection has been widespread in Hubei Province and in some areas the infection was serious attention should therefore be paid to its control without delay.


Paecilomyces lilacinus infection in a liver transplant patient: case report and review of the literature.
A 56-year-old male who was 12 months status post liver transplant presented with a 2-month history of painful, erythematous nodules over the right knee. Several biopsies yielded a mold initially phenotypically identified as a Penicillium species, but molecular sequence analysis ultimately determined the identity as Paecilomyces lilacinus. Several courses of oral voriconazole were required for resolution of the infection. A review of the literature revealed that Paecilomyces species are an infrequent cause of disease in transplant patients, with skin and soft tissue infections being the most common presentation. It is important to accurately identify these infections, and polymerase chain reaction assay using universal fungal primers offers a rapid and precise diagnostic approach. Treatment of Paecilomyces infections may require multiple courses of antifungal therapy, often with surgical debridement. We suggest that voriconazole may be a useful treatment alternative to the more traditional therapy with amphotericin B-based agents.


Links between hepatic fibrosis, ductular reaction, and progenitor cell expansion.
Interactions between cells and their extracellular matrix have been shown to be crucial in a wide range of biological processes, including the proliferation and differentiation of stem cells. Ductular reactions containing both hepatic progenitor cells and extracellular matrix are seen in response to acute severe and chronic liver injury. Understanding the molecular mechanisms whereby cell-matrix interactions regulate liver regeneration may allow novel strategies to enhance this process. Both the ductular reaction in humans and hepatic progenitor cells in rodent models are closely associated with collagen and laminin, although there is still debate about cause and effect. Recent studies have shown a requirement for matrix remodeling by matrix metalloproteinases for the proliferation of hepatic progenitor cells and suggested defined roles for specific matrix components. Understanding the interactions between progenitor cells and matrix is critical for the development of novel regenerative and antifibrotic therapies.


[Changes in serum levels of folic acid after total gastrectomy].
The Authors, in consideration that Folic Acid is assimilated in the upper alimentary tract, effected a comparative study between its seric levels in normal patients and in patients submitted to gastrectomy for gastric cancer, at different times from the operation. In the patients of the first group, Folic Acid levels were not correlated with sex, but to age, decreasing with the increasing of it. In gastrectomized patients, serum levels, also if acceptable, were always lower than in control cases, and gradually decreasing with the increasing of the age. The Authors conclude that, obviously, intestinal assimilation and endogenous reserves are able to counterbalance for enough long time the insufficient alimentary absorption.


Reproducibility of dual-energy X-ray absorptiometry in the upper extremities in stroke patients.
Bone mineral loss after stroke in affected extremities can increase the prevalence of fractures that interrupt the rehabilitation programme and lower the level of activity. In stroke rehabilitation, precise bone mineral measurement is needed in order to assess the risk of fractures. We defined five regions-of-interest of the upper extremity (proximal humerus, distal forearm, distal radius, distal ulna and hand) consistently, so that the position was comfortable for hemiplegic patients to maintain during the measurement. The aim of this study was to determine whether our method using dual-energy X-ray absorptiometry is useful in hemiplegic patients. Ten normal subjects and 15 hemiplegic patients were studied. In normal subjects the reproducibility of our method was evaluated by repeated measurements of both the right and left sides. In hemiplegic patients the reproducibility was evaluated by repeated measurements of the affected side. The coefficient of variation (CV) values were obtained for BMD (0.7-1.7%) and BMC (0.7-2.3%) in normal subjects, and BMD (1.3-2.1%) and BMC (1.7-5.4%) in hemiplegic patients. The CV for the side-to-side BMD and BMC ratios in the normal subjects ranged from 1.1% to 2.2% and from 1.8% to 3.1%, respectively. Our study shows that the reproducibility of our method is sufficient for application to hemiplegic patients.


Cysticercosis surveillance: locally acquired and travel-related infections and detection of intestinal tapeworm carriers in Los Angeles County.
A surveillance system for cysticercosis was initiated in January 1988 in Los Angeles County to measure the incidence of the disease, to more accurately assess the level of locally acquired and travel-related infection, and to evaluate household contacts for intestinal tapeworm infection. In three years of surveillance (1988-1990), 138 incident cases were reported for an average crude annual incidence rate of 0.6 per 100,000 population. The highest rates were among Hispanics (1.6/100,000), most of whom were Mexican immigrants. Eight (5.8%) cases were fatal. Nine (6.5%) probable travel-associated cases occurred among persons born in the United States who had traveled to Mexico. Ten (7.2%) autochthonous cases of cysticercosis were documented. Taenia eggs were recovered more commonly in specimens from contacts with cysticercosis cases (1.1%) than in specimens from noncontact patients (0.2%). At least one Taenia tapeworm carrier was found among contacts of five (6.9%) of 72 cysticercosis patients. Carriers were more likely to be found among contacts of patients born in the United States (22.2%) than among those of foreign-born (4.8%) patients (odds ratio = 5.4) Cysticercosis causes appreciable morbidity and mortality in Los Angeles County, principally among Hispanic immigrants. However, these results indicate that both travel-acquired and locally acquired cysticercosis may be more common than previously recognized. Public health followup of cysticercosis cases, including screening of household contacts, can identify tapeworm carriers, who can be treated and removed as potential sources of further infection.


Immunological Characteristics of Colitis Associated with Anti-CTLA-4 Antibody Therapy.
Anti-CTL4-A therapy is associated with development of colitis. We characterized ipilimumab-associated colitis in nine melanoma patients (6 male, mean age: 55.3-yrs). Median value for diarrhea grade was 2, number of ipilimumab doses 2, and interval since last administration 3-wks. Endoscopic characteristics resembled inflammatory bowel disease and histology revealed predominance of plasmacytes or CD4+ T-cells. We observed significant upregulation of Th1 and Th17 effector pathways (>10-fold increase for IFN-γmRNA, >5-fold for IL-17A, p < 0.01 vs. controls). Significant elevation of FoxP3 was also detected. In conclusion, ipilimumab administration results in elevations of effector lymphocytes and pro-inflammatory mediators in the gut lamina propria.


A prospective cohort study of injury incidence and risk factors in North Carolina high school competitive cheerleaders.
Cheerleaders suffer nearly half of catastrophic injuries observed in female scholastic athletes in the United States. However, incidence of noncatastrophic injury in this population has not been described. Coach, athlete, and injury circumstance variables may predict the injury rate among cheerleaders. Prospective cohort. The authors investigated injury incidence in a sample of North Carolina female cheerleaders who competed inter-scholastically from 1996 to 1999. Injury, exposure, and demographic data were collected from squads that participated in the North Carolina High School Athletic Injury Study. Cheerleaders suffered 133 injuries during 1701 athlete seasons. More than 21% of the injuries were ankle sprains. The injury rate was 8.7; the 95% confidence interval (CI) was 6.5 to 11.7 per 10,000 athlete exposures. In a multivariate Poisson regression model, cheerleaders supervised by coaches with the most education, qualifications, and training (coach EQT) had a nearly 50% reduction in injury risk (rate ratio [RR], 0.5; 95% CI, 0.3-0.9), and cheerleaders supervised by coaches with medium coach EQT had a nearly 40% reduction in injury risk (RR = 0.6; 95% CI, 0.3-1.2) compared to cheerleaders supervised by coaches with low coach EQT.


Cognitive impairment in the elderly diabetics.
In the elderly patients, cognitive impairment is often associated with diabetes, especially with memory loss. The underlying mechanism of this phenomenon have not been cleared up. Metabolic changes can play an important role, because either low or high blood sugar levels can affect the cognitive performance. Here we report our preliminary data from an ongoing study on cerebrovascular deficits in diabetic elderly patients.


Gas chromatographic-mass spectrometric quantitation of urinary buprenorphine and norbuprenorphine after derivatization by direct extractive alkylation.
A gas chromatographic-mass spectrometric procedure for the quantitation of buprenorphine and norbuprenorphine has been developed in which the analytes were converted, after enzyme hydrolysis, to their methyl derivatives by direct extractive alkylation using tetrahexylammonium hydrogen sulphate phase transfer reagent and iodomethane dissolved in tert.-butylmethyl ether. The procedure utilised a sample volume of 2 ml and gave a detection limit of 0.2 ng ml(-1) for buprenorphine and norbuprenorphine. The buprenorphine and norbuprenorphine standard curves were linear in the concentration range of 1-100 ng ml(-1) with r=0.999. The coefficients of variation for the intra-run precision were 1.3% for buprenorphine and 8.8% for norbuprenorphine (n=10). The coefficients of variation for the inter-run precision were 7.7% for buprenorphine and 10.1% for norbuprenorphine (n=5). The method recovery was 92% (C.V.=3.3%) for buprenorphine and 104% (C.V.=2.9%) for norbuprenorphine (n=10).


Correlation between electrophysiological phenomena and transport of macromolecules in intestinal epithelium.
This review discuss some recent findings in the study of the regulation of the permeability of the intestinal epithelial layer. Comparison of electrical phenomena and transport of macromolecules suggests that secretory activity and increased transepithelial transport of macromolecules are related when secretion is mediated by the Ca2+ and PKC dependent pathways. The transport of the macromolecules is via the transcellular and via the paracellular route. The barrier function of the intestinal epithelium may be diminished during nervous (acetylcholine)- and immuno-(histamine) mediated secretion. It is hypothesised that some bacterial toxins may also induce Ca2+ and PKC dependent secretion and thereby can reduce the epithelial barrier. The cAMP and cGMP mediated secretion, which can be recognised by their long-lasting transepithelial potential changes, are not coupled to increased transepithelial transport of macromolecules. Some forms of secretory diarrhea may therefore be related to the development of food-allergy or inflammation.


Treatment of male pattern baldness and postoperative temporal baldness in men.
The use of plastic surgery techniques such as flaps and reductions has resulted in dramatic progress in the treatment of baldness. The operative indications are difficult because of the variety of baldness and the multiple techniques available. Surgeons place themselves at a disadvantage by refusing a specific technique, and this may harm the patient. Surgeons should establish a careful plan before undertaking the treatment of a patient, to make maximum use of the techniques that are available. We prefer flaps and reductions to grafts because of the decrease in the number of operations and time required to obtain a good result. We have described our personal classification, which takes into account the distribution of the hair, the density in each region, and the position of the frontal and temporal hairlines. This enables us to be more precise as to the indications and limitations of surgery. Different modern techniques have been described, concentrating on major reductions or scalp lifts as described by the author, which results in advancement of the crown 6 cm posteriorly and between 2 and 3 cm laterally. Dramatic results can be obtained if one or two vertical flaps are raised during the same operation. Vertical flaps provide a better result than horizontal flaps because they provide a deep android recession and natural forward hair growth. These techniques have the advantage of providing a rapid and aesthetic result after each operation as compared with punch grafts, which require long periods of time before obtaining a reasonable result. Finally, we propose a rapid, easy, two-stage procedure for extensive baldness that combines a one-stage preauricular flap with a scalp lift. The aesthetic result is good and may be completed by another reduction or by punch grafts.


Echinococcus granulosus equinus: an ultrastructural study of murine tissue response to hydatid cysts.
Peritoneal hydatids of Echinococcus granulosus equinus of 9 months standing in BALB/c mice occurred as free cysts or cysts within cyst masses. Both showed wide variation in size and in host tissue response, and all had a well-developed laminated layer separating the host tissue response from the germinal layer. In the smallest cyst-mass cysts the host tissue response was present as remnants of the initial cellular attack involving eosinophils. Slightly larger cyst-mass cysts possessed a primary macrophage invasion which phagocytosed the remnants of the initial attack and also, though to little effect, the laminated layer material. In the largest cyst-mass cysts a second macrophage invasion, of monocyte origin, had commenced and transformation stages of these cells to macrophages were observed. No fibroblasts surrounded individual cyst-mass cysts but they were present around the cyst mass, encapsulating it and possibly preventing further host cell invasion. Thus, the host tissue response around individual cyst-mass cysts remained 'preserved' at an early stage such as existed at the time of encapsulation. Small free cysts showed a primary macrophage invasion and transformation stages of cells of a secondary infiltration of peritoneal origin. Peripheral to the macrophages were fibroblasts demonstrating limited fibrinogenesis, and each cyst was surrounded by a layer of mesothelial cells. Large free cysts, also delimited by a mesothelial layer, possessed peripheral connective tissue, a deep fibrous layer and a monolayer of very compressed macrophages lying adjacent to the laminated layer. It is emphasized that an understanding of the host tissue response in cysts of different sizes and from different locations is an essential pre-requisite for the design of experimental studies.


Cyanoacrylate adhesive with conjunctival resection and superficial keratectomy in Mooren's ulcer.
Seventeen eyes of thirteen patients with Mooren's ulcer were treated with a combination therapy of local and systemic steroids, conjunctival resection, superficial keratectomy and application of cyanoacrylate tissue adhesive. The pathology was classified as acute, subacute and chronic. Ulcers were graded based on the extent of corneal thinning, degree and extent of ulceration, and amount of inflammation. Fourteen eyes (82.4%) healed completely with formation of a vascularised scars, while three eyes (17.6%) failed to respond to treatment and either went into phthisis bulbi or healed with gross tissue distortion. Our study suggests an early intervention of this therapy with cyanoacrylate tissue adhesive application for effective control of Mooren's ulceration.


Prognostic implications of lymphadenectomy in esophageal cancer after neo-adjuvant therapy: a single center experience.
The objective of this study is to explore the prognostic implications of lymphadenectomy in esophageal cancer patients after neo-adjuvant therapy. Retrospective review of a prospectively maintained database identified esophageal cancer patients with locoregional disease who received neo-adjuvant therapy and surgery. Patients were grouped based on the number of nodes resected, pathological lymph node status, and percentage of positive nodes. Kaplan-Meier curves were used to analyze overall survival (OS) and disease-free survival (DFS). Log-rank test was used to compare survival between groups. Eighty-four patients formed the study group. Patients with ≥ 18 nodes resected had a significantly longer median OS than those with <18 nodes resected (68.6 vs. 29.6 months; p = 0.014). Lymph node-negative patients had significantly longer median OS (51.4 vs. 27.4 months; p = 0.025) and DFS (45.3 vs. 12.9 months; p = 0.03) when compared to lymph node-positive patients. Patients with a percentage of positive nodes <0.25 had a significantly longer median OS (31.1 vs. 17.8 months; p = 0.015) and DFS (21.7 vs. 8.9 months; p = 0.021) than patients with ≥ 0.25% positive. Extent of lymphadenectomy, percentage of positive nodes, and pathological lymph node status are significant prognostic markers in patients who undergo esophagectomy after neo-adjuvant therapy.


Scientific Meetings.
In the "Preliminary announcement of the seventh New York AAAS meeting," 25 May issue, page 949, the name "Society of Vertebrate Zoology" was mistakenly given as one of the cosponsors of the symposium on "Biotic communities in the past and today." The correct name of the society referred to is Society of Vertebrate Paleontology.


Prospective evaluation of carcinoembryonic antigen levels and alternating chemotherapeutic regimens in metastatic breast cancer.
Ninety-seven eligible and evaluable women with metastatic breast cancer were placed on a prospective clinical protocol to evaluate the use of continuous cyclic therapy with dibromodulcitol, doxorubicin, vincristine, tamoxifen, and fluoxymesterone (DAVTH) v DAVTH alternating with cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP); and the use of pretreatment and serial carcinoembryonic antigen (CEA) levels in these patients. Continuous DAVTH and DAVTH/CMFP were equivalent therapies with respect to response rates, time to treatment failure (TTF), and survival. Pretreatment CEA levels were elevated (greater than 5 ng/mL) in 42/97 patients and less than 5 ng/mL in the remaining patients. Patients with elevated pretreatment CEA levels were more likely to be estrogen receptor (ER) positive (P = .006), to have prolonged disease-free intervals (P = .017), to have hepatic (P = .004) and/or osseous (P = .01) metastases, and to have multiple sites of metastatic disease (P = .004). Pretreatment CEA levels did not significantly predict for overall response rates, TTF, or survival; nonetheless, those patients with low pretreatment CEA levels had more complete responses (CRs) (16/55 v 4/42; P = .02). Serial CEA levels during therapy revealed a number of interesting patterns. During the first 4 months of treatment, serial CEA levels in responding patients either (1) progressively declined (15/29 women with elevated pretreatment CEA levels), or (2) initially rose significantly (mean, 243% of pretreatment value) and then declined (14/29 women with elevated pretreatment CEA levels). Peak CEA levels in the latter patients were seen 27 to 135 days following initiation of cytotoxic therapy. In some patients the initial increase in the CEA level was incorrectly interpreted as evidence of impending disease progression. CEA levels frequently increased around the time of clinical disease progression. However, rising CEA levels rarely provided a clinically meaningful lead time before the appearance of other clinical evidence of disease progression. These data suggest that routine pretreatment and monthly serial CEA levels in metastatic breast cancer patients have minimal use in clinical practice. Two further noteworthy findings were observed in this prospective study. First, patients with an unknown ER status had a prolonged median survival when compared with patients with ER positive or negative tumors; this appeared to be related to prolonged disease-free intervals in ER unknown patients. Second, two case of secondary acute leukemia were seen in patients treated with continuous DAVTH therapy.


Liver Receptor Homolog-1 Regulates Organic Anion Transporter 2 and Docetaxel Pharmacokinetics.
Organic anion transporter 2 (OAT2/SLC22A7) is an uptake transporter that plays an important role in drug disposition. Here, we investigate a potential role of liver receptor homolog-1 (Lrh-1) in regulation of Oat2 and docetaxel pharmacokinetics. Hepatoma cells (Hepa1-6 and HepG2 cells) were transfected with Lrh-1/LRH-1 expression vector or siRNA. The relative mRNA and protein levels of Oat2/OAT2 in the cells or livers of Lrh-1hep-/- mice were determined by qPCR and Western blotting, respectively. Transcriptional regulation of Oat2/OAT2 by Lrh-1/LRH-1 was investigated using luciferase reporter, mobility shift, and chromatin immunoprecipitation (ChIP) assays. Pharmacokinetic studies were performed with wild-type (Lrh-1fl/fl) and Lrh-1hep-/- mice after intraperitoneal injection of docetaxel. Overexpression of Lrh-1 in Hepa1-6 cells led to significant increases in Oat2 mRNA and protein. Consistently, Lrh-1 knockdown caused decreases in Oat2 mRNA and protein, as well as reduced cellular uptake of PGE2, a prototypical substrate of Oat2. Similarly, an activation effect of LRH-1 on OAT2 expression was observed in HepG2 cells. In addition, the levels of Oat2 mRNA and protein were markedly reduced in Lrh-1hep-/- mice. Lrh-1/LRH-1 induced the transcription of Oat2/OAT2 in luciferase reporter assays. Truncation analysis revealed a potential Lrh-1 response element (-716- to -702-bp) in Oat2 promoter. Direct binding of Lrh-1 to this response element was confirmed by mobility shift and ChIP assays. Furthermore, systemic exposure of docetaxel was upregulated in Lrh-1hep-/- mice due to reduced hepatic uptake. In conclusion, Lrh-1 transcriptionally regulates Oat2, thereby impacting tissue uptake and pharmacokinetics of Oat2 substrates.


Exploring National Surgical Quality Improvement Program respiratory comorbidities: developing a predictive understanding of postoperative respiratory occurrences, Clavien 4 complications, and death.
For preoperative risk stratification, little is known about the implications of respiratory comorbidities in relation to postoperative complications in the diverse population of surgical patients. We hypothesized that patients with preoperative respiratory comorbidities would be at increased risk of postoperative respiratory occurrences and death. Under the data use agreement and with the approval of the Henry Ford Health System Institutional Review Board (IRB #6830), we reviewed 5 y (2005-2009) of National Surgical Quality Improvement Program participant use files. Respiratory comorbidities were defined as current smoker, chronic obstructive pulmonary disease, dyspnea, and current pneumonia. Respiratory outcomes tracked in the National Surgical Quality Improvement Program included reintubation, postoperative pneumonia, and prolonged ventilation. We defined Clavien 4 and 5 outcomes to include postoperative septic shock, postoperative dialysis, pulmonary embolism, myocardial infarction, cardiac arrest, prolonged ventilatory requirements, need for reintubation, and death. Of 971,455 patients identified, 361,412 had respiratory comorbidities. As the number of respiratory comorbidities increased, we found a statistically significant increase in the occurrence of postoperative respiratory adverse events, including Clavien 4 and 5 complications. Multivariate regression analysis showed that respiratory comorbidities and age were independent predictors of mortality. All data reported here were significant at P < 0.001. This study showed a significant association between respiratory comorbidities and postoperative adverse events, including Clavien 4 complications and death. Further prospective studies are required to explore this association.


The anti-tumor agent sagopilone shows antiresorptive effects both in vitro and in vivo.
Sagopilone, a fully synthetic epothilone and very potent anti-tumor agent, has proved to be efficient in inhibiting bone destruction and tumor burden in a mouse model of breast cancer bone metastasis. In addition to its antiproliferative effects, this study shows direct effects of sagopilone on bone resorption and osteoclast activity. Sagopilone, a novel fully synthetic third-generation epothilone, has proved to be efficient in inhibiting bone destruction and tumor burden in a mouse model of breast cancer bone metastasis. The aim of this study was to investigate whether the effect was primarily due to sagopilone's antiproliferative effect and consequent inhibition of tumor cell growth, or if sagopilone exerts direct effects on bone resorption and osteoclast activity. Sagopilone was studied and compared to paclitaxel in vitro in human osteoclast differentiation and activity cultures. For studying the potential of sagopilone for inhibiting bone resorption in vivo, a mouse model of ovariectomy (ovx)-induced osteoporosis was utilized. Sagopilone inhibited osteoclast differentiation and activity more efficiently than paclitaxel and showed less cytotoxicity. Whereas sagopilone showed inhibitory effects on human osteoclast differentiation and activity already at 5 and 15 nM, respectively, paclitaxel started to show effects only at 20 and 100 nM concentrations, respectively. Sagopilone treatment increased BMD In the mouse ovx model even though a non-optimized dose was used which is effective in tumor-bearing mice. This is the first study to evaluate sagopilone's effects on bone resorption in non-cancerous situation. The evidence that sagopilone is beneficial for bone will strengthen the status of sagopilone as an anti-cancer compound compared to other microtubule stabilizing agents.


Increase in prostate stem cell antigen expression in prostatic hyperplasia induced by testosterone and 17β-estradiol in C57BL mice.
Estradiol (E2) is known to act synergistically with testosterone (T) for the development of prostatic hyperplasia in rats and dogs, but murine prostate is less responsive to hormonal stimulation. However, a recent study revealed that the combined administration of E2 and T induced prostatic hyperplasia with bladder outlet obstruction in C57BL mice. To understand the mechanisms underlying the hormonal induction of prostatic hyperplasia, the expression of growth factors and their receptors, androgen receptor, estrogen receptor (ER), and prostatic secretory proteins was investigated. Ten-week-old male C57BL mice were treated with T (30mg) or T+E2 (0.5mg) for 10 weeks, and prostatic lobes were dissected and subjected to quantitative RT-PCR and immunoblotting analysis. T administration appeared to induce glandular prostatic growth, while with T+E2 administration this growth was greater and accompanied by extreme bladder enlargement. The expression of prostate stem cell antigen (PSCA) mRNA and protein was increased in prostate tissue in the T group. The combined administration of E2 with T prominently enhanced PSCA expression, along with increased insulin growth factor 1 mRNA levels and decreased estrogen receptor β mRNA expression. The synergistic effect of E2 on the expression of PSCA suggests that this protein may play an important role in the hormone-induced development of prostatic hyperplasia.


Fatty acid composition of some medicinally useful seeds.
Fatty acid composition of seeds from the fruits of Butea monosperma, Jatropha glandulifera and Portulaca oleracea of three different families, namely Papilionaceae, Euphorbiaceae and Portulaceae were determined through Gas Liquid Chromatography to find novel natural sources of essential fatty acids for human health and of economic interest. Comparative studies were also performed to ascertain the utilization of each species for domestic as well as industrial purpose and the quality parameters developed can be utilized as marker characters for the aforesaid seeds used by the pharmaceutical industries.


Matrix metalloproteinase 7, soluble Fas and Fas ligand serum levels for predicting docetaxel resistance and survival in castration-resistant prostate cancer.
To assess the predictive value of pre-chemotherapy matrix metalloproteinase 7 (MMP-7), soluble Fas (sFas) and Fas ligand (FasL) serum levels, as well as their changes during therapy. Serum levels of MMP-7, Fas and FasL were determined by ELISA in 96 patients with castration-resistant prostate cancer (CRPC): 21 docetaxel-resistant patients who received one single series and 75 docetaxel-sensitive patients who received repeated series of docetaxel. In addition to the 96 pretreatment serum samples, 987 sera collected during chemotherapy were also analysed. Higher pretreatment serum MMP-7, sFas and prostate-specific antigen (PSA) levels were significantly associated with both docetaxel resistance (P = 0.007, P = 0.001, P < 0.001, respectively) and shorter cancer-specific survival (P < 0.001, P = 0.041, P < 0.001, respectively). High MMP-7 level remained an independent predictor of both docetaxel resistance (hazard ratio [HR] 2.298, 95% confidence interval [CI]: 1.354-3.899; P = 0.002) and poor cancer-specific survival (HR 2.11, 95% CI: 1.36-3.30; P = 0.001) in multivariable analyses. Greater increase in MMP-7 levels in the second treatment holiday and greater increase in PSA levels in the first and second treatment holidays were predictive of survival. Pretreatment serum MMP-7 levels may help to select patients with CRPC who are likely to benefit from docetaxel chemotherapy. Furthermore, MMP-7 levels alone or in combination with PSA levels could be used for therapy monitoring. Correlative studies embedded in clinical trials are necessary to validate these biomarkers for clinical decision-making.


The significance of in vitro rat skin absorption studies to human risk assessment.
The present paper reviews the comparative rates of skin penetration between rat and man for a total of 14 chemicals in in vitro absorption studies. The results showed that in vitro absorption assays are capable of demonstrating large differences in the rate of skin penetration. Saturation of absorption was also frequently observed at higher exposure levels. The highest absorption rates through rat and human epidermis were observed with compounds with a molecular weight of approximately 300, an aqueous solubility of approximately 1-6 mg/l, and a log10 (P(OCTANOL/WATER)) of approximately 3-4. When the absorption data for 3 compounds with a log10 (P(OCTANOL/WATER)) of 2.9-3.0 were compared, there appeared to be an inverse relationship between molecular weight/aqueous solubility and the rate of dermal absorption. Lipophilic compounds with low aqueous solubility (<4 mg/l) showed the highest penetration rates through rat skin, but this was not always the case for human skin. The human skin was invariably less permeable to all tested substances than rat skin, though no constant factor of difference could be identified. The factor of difference would not appear to be determined by molecular weight, lipophilicity, or aqueous solubility. The actual systemic exposure of humans may be significantly overestimated if risk assessment is based only on the results of an in vivo rat study. It would appear that dermal penetration through human skin should be based on the combined use of in vivo and in vitro data, using the following equation: %Human dermal penetration= [[% dermal penetration rat (in vivo)] x [rate dermal penetration human (in vitro)]] / [rate dermal penetration rat (in vitro)]


Nonoxovanadium(IV) and oxovanadium(V) complexes with mixed O, X, O-donor ligands (X = S, Se, P, or PO).
Ligating properties of four potentially tridentate bisphenol ligands containing [O, X, O] donor atoms (X = S 1, Se 2, P 3, or P=O 4) toward the vanadium ions in +IV or +V oxidation states have been studied. Each ligand with different heterodonor atoms yields as expected nonoxovanadium(IV) complexes, V(IV)L(2), whose structures have been determined by X-ray diffraction methods as having six-coordinate V(IV), VO(4)X(2), core. Compounds 1-4 have also been studied with electrochemical methods, variable-temperature (2-295 K) magnetic susceptibility measurements, X-band electron paramagnetic resonance (EPR) (2-60 K) spectroscopy, and magnetic circular dichroism (MCD) (5 K) measurements. Electrochemical results suggest metal-centered oxidations to V(V) (i.e., no formation of phenoxyl radicals from the coordinated phenolates). A combination of density functional theory calculations and experimental EPR investigations indicates a dramatic effect of the heteroatoms on the electronic structure of 1-4 with consequent reordering of the energy levels; 1 and 3 possess a trigonal ground state (d(z)()(2))(1), but 4 with the phosphoryl oxygen as the heterodonor atom in contrast exhibits a tetragonal ground state, (d(xy)())(1). On the basis of the intense electronic transitions in absorption spectra, all electronic transitions observed for 4 have been assigned to ligand-to-metal charge-transfer transitions, which have been confirmed by preliminary resonance Raman measurements and C/D ratios obtained from low-temperature MCD spectroscopy. Moreover, diamagnetic complexes 5 and 6 containing mononuclear and dinuclear oxovanadium(V) units have also been synthesized and structurally and spectroscopically ((51)V NMR) characterized.


The Chédiak-Higashi syndrome: CT and MR findings.
Chédiak-Higashi syndrome (CHS) is a rare autosomal recessive disorder postulated to result from lack of regulation of fusion of the primary lysosomes. In this report we present the MR and CT features of the brain in a patient with known CHS. These findings include diffuse atrophy of the brain with diffuse periventricular decreased density identified with CT, as well as increased signal on the T2-weighted images and lack of enhancement on the T1-weighted images in the periventricular and corona radiata regions.


Non-equilibrium thermodynamics and degenerate disease.
Non-equilibrium thermodynamics, biochemistry and physiology can be associated to form a possible foundation for a theory of nutritional medicine. The theory predicts a new class of diseases. The relationship between this new class and cancer is discussed.


The role of echocardiography in diagnosis and management of isolated meningococcal pericarditis.
Although pericarditis may complicate the course of meningococcemia, it is distinctly unusual as a presenting sign. Herein we report a case of a previously healthy 16-year-old male with isolated meningococcal pericarditis, in which transthoracic echocardiography was of great importance for the initial diagnosis and for guiding the therapeutic approach during the hospitalization period. The patient presented with symptoms of chest pain and fever that deteriorated into cardiac tamponade. Pericardiocentesis was successful and Neisseria meningitidis was identified as the causative agent in the pericardial fluid. Because of failure of clinical resolution, echocardiogram was repeated and showed evidence of maintenance of large echo dense content in pericardial space. The presence of purulent content was confirmed during open-chest surgery. The role of echocardiography for the correct management of this rare form of pericarditis is discussed.


Clinical features and biological implications of different U2AF1 mutation types in myelodysplastic syndromes.
U2AF1 mutations (U2AF1MT) occur commonly in myelodysplastic syndromes (MDS) without ring sideroblasts. The aim of this study was to investigate the clinical and biological implications of different U2AF1 mutation types in MDS. We performed targeted gene sequencing in a cohort of 511 MDS patients. Eighty-six patients (17%) were found to have U2AF1MT, which occurred more common in younger patients (P = .001) and represented ancestral lesions in a substantial proportion (71%) of cases. ASXL1MT and isolated +8 were significantly enriched in U2AF1MT-positive cases, whereas TP53MT, SF3B1MT, and complex karyotypes were inversely associated with U2AF1MT. U2AFS34 subjects were enriched for isolated +8 and were inversely associated with complex karyotypes. U2AF1MT was significantly associated with anemia, thrombocytopenia, and poor survival in both lower-risk and higher-risk MDS. U2AF1S34 subjects had more frequently platelet levels of <50 × 109 /L (P = .043) and U2AF1Q157 /U2AF1R156 subjects had more frequently hemoglobin concentrations at <80 g/L (P = .008) and more often overt fibrosis (P = .049). In conclusion, our study indicates that U2AF1MT is one of the earliest genetic events in MDS patients and that different types of U2AF1MT have distinct clinical and biological characteristics.


Activation of the secretory pathway leads to a decrease in the intracellular amyloidogenic fragments generated from the amyloid protein precursor.
The activation of the secretory pathway for the amyloid protein precursor (APP) by phorbol 12-myristate 13-acetate in human glioblastoma A-172 cells leads to a decrease in intracellular beta-amyloidogenic fragments derived from APP. The result suggests that a metabolic switch of APP from the endosomal/lysosomal pathway to a secretion route occurs after PMA treatment.


Laparoscopic treatment of acute mesenteric torsion.
Acute torsion of the small bowel mesentery is a diagnostically challenging cause of acute abdominal pain, which most commonly afflicts pediatric patients with midgut malrotation. We describe a case of mesenteric torsion in an adult patient that had manifested as acute abdominal pain. The patient had a remote history of prior abdominal surgery, presenting on multiple occasions with undiagnosed acute intermittent abdominal pain. Diagnosis of mesenteric torsion was made by contrast enhanced CT and the ailment was successfully treated with laparoscopic surgery without recurrence.


[Modification of Derzhavin sphyncteroplasty and elimination of symphysis diastasis of the pubic bone in severe epispadia].
In 1990-2006 Tashkent Medical Academy Clinic admitted 71 patients (63 boys and 8 girls) with subtotal and total forms of epispadia which in some cases combined with extrophy of the bladder. Thirty-nine patients of this group were treated with conventional Derzhavin sphynctroplasty with suturing the borders of the pubic symphysis. Urinary incontinence was eliminated partially or completely in 72.3% cases, diastasis of pubic symphasis was not corrected. Thirty two patients were treated with modified Derzhavin sphyncteroplasty and an original technique of symphysis diastasis correction. Good and satisfactory results were obtained in 90.6% patients. X-ray detected no cases of divergence of symphysis 2 months after surgery.


Intraabdominal abscess related fungaemia caused by Rhodotorula glutinis in a non-neutropenic cancer patient.
Rhodotorula glutinis is a rare fungal infection that is especially observed in immune-compromised patients. It is common in the skin, faeces, nails, sputum, gastrointestinal system and adenoid tissue. However, the incidence of Rhodotorula glutinis is increased in both local and systemic infections in recent years. Presented here is a case of Rhodotorula glutinis fungaemia that isolated from subhepatic abscess formation and blood in a patient who was operated with Roux-en-Y technique due to gastric adenocarcinoma. Fungal sepsis is an important cause of fever resistant to antibiotic therapy that is often taken into marginal account. It should instead be particularly considered in patients with a history of intraabdominal surgery and non-neutropenic cancer patients. The case described illustrates an episode of systemic infection by Rhodotorula glutinis, correlated with the presence of intraabdominal abscess and without central venous catheters. This is the first case of fungaemia by Rhodotorula glutinis with an intraabdominal abscess source reported from Turkey.


Low prevalence of p.G352fsdelG mutation in phenylketonuria patients from Morocco.
Frameshift mutation p.G352fsdelG in the PAH gene was recently reported as the most common mutation in Moroccan patients with phenylketonuria (PKU). This result, if confirmed, would considerably facilitate genetic counseling and molecular diagnosis of the disease in Morocco. Given that the incidence of PKU in the Mediterranean region is estimated at between 1/4000 and 1/10,000, this mutation would be harbored by many Moroccans. We aimed to estimate the frequency of heterozygotes for the p.G352fsdelG mutation in Moroccan newborns. In this study, we used a reliable TaqMan(®) real-time polymerase chain reaction to detect the mutation p.G352fsdelG in the PAH gene in 250 unrelated Moroccan newborns. DNA was extracted from umbilical cord blood with maternal consent. The supposed recurrent mutation p.G352fsdelG was found in none of the 250 tested newborns. Therefore, the frequency of heterozygotes for this mutation would be less than 1/250, and the incidence of patients with PKU homozygous for this mutation would not exceed 1/100,000. The p.G352fsdelG mutation in the PAH gene does not appear to be prevalent in the Moroccan population and would be responsible for only few cases of PKU. The previous report of this anomaly as being responsible for 62.5% of PKU patients in Morocco could be explained by selection bias.


Variability, agreement and reliability of MRI knee landmarks.
Surface mesh reconstructions of bones are often required to define landmark-based coordinate systems, regions of interest and morphological features when studying the soft tissues of the knee from MRI scans. This study reports the variability, agreement and reliability of osseous landmarks to better understand their downstream effects. Fifteen landmarks were defined on the distal femur and twelve on the proximal tibia. Surface meshes were created from twenty right knee MRI scans with a mean subject age of 30.9 years. A single observer identified landmarks on all twenty knees, while three observers repeated the observations three times on a subset of eight knees. All observations were aligned to the Procrustes mean shapes. Principal component analysis was used to study inter-subject variability and two-way ANOVA for inter- and intra-observer agreement and reliability. Inter-subject landmark variation ranged from 0.6 to 5.26 mm, while inter- and intra-observer agreement were at most 5.1 and 5.69 mm respectively. Between-observer reliability ranged from 0.07 to 0.98 while within-observer values were between 0.51 and 0.98. Landmarks derived from fitted spheres or circles often performed well, while most others had their poorest agreement or greatest variation limited to only one or two cardinal directions.


Isolation of Burkholderia cepacia JB12 from lead- and cadmium-contaminated soil and its potential in promoting phytoremediation with tall fescue and red clover.
Phytoremediation combined with suitable microorganisms and biodegradable chelating agents can be a means of reclaiming lands contaminated by toxic heavy metals. We investigated the ability of a lead- and cadmium-resistant bacterial strain (JB12) and the biodegradable chelator ethylenediamine-N,N'-disuccinic acid (EDDS) to improve absorption of these metals from soil by tall fescue and red clover. Strain JB12 was isolated from contaminated soil samples, analysed for lead and cadmium resistance, and identified as Burkholderia cepacia. Tall fescue and red clover were grown in pots to which we added JB12, (S,S)-EDDS, combined JB12 and EDDS, or water only. Compared with untreated plants, the biomass of plants treated with JB12 was significantly increased. Concentrations of lead and cadmium in JB12-treated plants increased significantly, with few exceptions. Plants treated with EDDS responded variably, but in those treated with combined EDDS and JB12, heavy metal concentrations increased significantly in tall fescue and in the aboveground parts of red clover. We conclude that JB12 is resistant to lead and cadmium. Its application to the soil improved the net uptake of these heavy metals by experimental plants. The potential for viable phytoremediation of lead- and cadmium-polluted soils with tall fescue and red clover combined with JB12 was further enhanced by the addition of EDDS.


[Surgical treatment for cancer of the pancreatic head].
To explore and evaluate the therapeutic efficacy of surgical treatment for cancer of the pancreatic head. The clinical data of 96 patients with cancer of the pancreatic head admitted in our hospital from January 2002 to December 2009 were retrospectively analyzed. pancreatoduodenectomy was performed in 48 cases, extended pancreatoduodenectomy in 30 cases, and Roux-Y cholangiojejunostomy in 18 cases. The 1, 2 and 3-year survival rates were 59.2%, 41.8% and 13.2%, respectively, in the patients treated with pancreatoduodenectomy, and 73.2%, 58.2% and 24.1%, respectively, in the patients treated with extended pancreatoduodenectomy. The 1, 2 and 3-year survival rates were 36.8%, 15.8% and 5.3%, respectively, in the patients with unresectable tumor who received radiotherapy and (or) chemotherapy in Roux-Y cholangiojejunostomy. The postoperative morbidity was 29.2%, 30.0% and 27.8% in the patients treated with pancreatoduodenectomy, extended pancreatoduodenectomy and Roux-Y cholangiojejunostomy, respectively. Pancreatoduodenectomy is the most effective treatment. Extended pancreatoduodenectomy can improve the surgical resection rate, reduce the recurrence rate and improve the survival rate. Internal drainage is an important palliative measure.