Seizure activity following cochlear implantation: is it the implant?
Cochlear implantation is a successful method of auditory rehabilitation. This procedure has been associated with facial nerve and vestibular end-organ stimulation suggesting potential for extra-cochlear stimulation. The objectives of this study were to investigate the potential relationship between cochlear implantation and seizure activity in the pediatric implant population. Local Research Ethics Board approval was obtained. The Hospital for Sick Children's Cochlear Implant Database from 1998 to 2011 was retrospectively reviewed. Based on a multidisciplinary team, patients who received a diagnosis of seizure disorder or had been investigated for seizure-like activity were identified and reviewed. Fifteen children from a group of 816 pediatric cochlear implant users were identified as having suspected seizure-like activity. Eventually 10 children were found to have seizures based on an evaluation by a pediatric neurologist and an electroencephalogram. Of these 10, only 3 children had new onset of seizures after cochlear implantation and 2 of these 3 suffered from global developmental delay and other medical comorbidities. No definite temporal connection was found between cochlear implant use and seizure activity. Cochlear implantation in the pediatric population continues to be a reliable and safe intervention for children. Overall the prevalence of post implantation seizure disorders in our population (0.37%) is lower than that of the overall population (0.5-1%). The presence of new-onset seizure activity following cochlear implantation is unusual and while there are theoretic possibilities of how a cochlear implant could be implicated in initiating seizures we were unable to find evidence to support this association.


Discovery and biosynthetic assessment of 'Streptomyces ortus' sp. nov. isolated from a deep-sea sponge.
The deep sea is known to host novel bacteria with the potential to produce a diverse array of undiscovered natural products. Thus, understanding these bacteria is of broad interest in ecology and could also underpin applied drug discovery, specifically in the area of antimicrobials. Here, we isolate a new strain of Streptomyces from the tissue of the deep-sea sponge Polymastia corticata collected at a depth of 1869 m from the Gramberg Seamount in the Atlantic Ocean. This strain, which was given the initial designation A15ISP2-DRY2T, has a genome size of 9.29 Mb with a G+C content of 70.83 mol%. Phylogenomics determined that A15ISP2-DRY2T represents a novel species within the genus Streptomyces as part of the Streptomyces aurantiacus clade. The biosynthetic potential of A15ISP2-DRY2T was assessed relative to other members of the S. aurantiacus clade via comparative gene cluster family (GCF) analysis. This revealed a clear congruent relationship between phylogeny and GCF content. A15ISP2-DRY2T contains six unique GCFs absent elsewhere in the clade. Culture-based assays were used to demonstrate the antibacterial activity of A15ISP2-DRY2T against two drug-resistant human pathogens. Thus, we determine A15ISP2-DRY2T to be a novel bacterial species with considerable biosynthetic potential and propose the systematic name 'Streptomyces ortus' sp. nov.


Modulation of the expression of the VIP receptor by serum factors on the human melanoma cell line IGR39.
IGR39 cells, isolated from a human superficial melanoma, display at their surface high and low affinity receptors for the vasoactive intestinal peptide (VIP). When grown in DME medium supplemented with 10% fetal calf serum, cells display 1.6 x 10(5) high affinity (Kd 0.74 nM) and 5.6 x 10(5) low affinity (Kd 55 nM) VIP binding sites per cell. When cultured in a chemically defined medium containing EGF, transferrin, and selenium, IGR39 cells display many neurite-like extensions. Following these morphological changes, the specific [125I]VIP binding is increased four- to fivefold after 6 days in culture. This phenomenon is reversible and is the result of an increased number of VIP binding sites available at the cell surface, without modification of their affinities. The molecular mass of the binding sites is also unchanged whatever cell culture conditions. Increase in [125I]VIP binding is inversely correlated to the serum concentration in the culture medium. When added to the chemically defined medium, sera from various origins as well as some serum substitutes reduce [125I]VIP binding to the same extent as that of the serum. The total cAMP production by VIP-stimulated IGR39 cells is enhanced by a factor of six to seven when cells are cultured in serum-free medium, in good correlation with the increase of VIP binding capacity. These data suggest that factor(s) present in fetal calf serum inhibit(s) the expression of VIP receptor, thus demonstrating the importance of a strict control of cell culture conditions for in vitro studies.


Meningococcal vaccines and protein-energy undernutrition in children in the African meningitis belt.
Vaccines to prevent meningococcal meningitis in the African meningitis belt include PsACWY, a polysaccharide-only vaccine; and PsA-TT, a polysaccharide-protein conjugate vaccine. Protein-energy undernutrition, a condition where children do not receive enough macro- or micronutrients, is related to increased risk of infectious diseases and poor immune function. Reduced immune function could affect vaccine immunogenicity. We investigated connections between protein-energy undernutrition and vaccine immunogenicity and antibody waning to PsACWY and PsA-TT in children in the African meningitis belt. This is a secondary analysis of data collected as part of four clinical trials testing the safety and efficacy of PsA-TT in children in Mali, Ghana, and Senegal. We identified whether anthropometric growth indices (low height-for-age, weight-for-height, or weight-for-age Z-score categories) were related to reduced vaccine-elicited antibody (measured with rabbit complement) from pre- to 1 month post-vaccination, in linear regression models. We also identified whether these growth indices were related to increased waning for vaccine-elicited antibody over time, in linear regression models. A total of 697 children were included in our analysis, of which 350 (50.2%) were female; the mean (SD) age was 1.0 (1.1) years, and 578 (83.0%) received PsA-TT. In linear regression models, no consistent statistical relationship was seen between pre-vaccination anthropometric Z-score categories and vaccine immunogenicity, or decline in antibody over time, for either vaccine, although children with low weight-for-height had a greater decline in antibody from 1 to 6 months post-vaccination. Our analysis did not find protein-energy undernutrition to be associated with immunogenicity or waning of PsACWY- or PsA-TT-elicited antibody in children living in the African meningitis belt. Future studies should consider measuring antibody titers at additional time points post-vaccination, and for longer periods of time, to determine if the rate of antibody waning over a period of several years is associated with protein-energy undernutrition.


Salivary excretion of amobarbital in man.
The concentrations of amobarbital in saliva and serum were determined in 5 normal adults following ingestion of 120 mg of sodium amobarbital. There was excellent linear relationship between amobarbital concentrations in saliva and serum (r = 0.993); salivary levels were 36.1% of serum levels. Since the pH of saliva was generally lower than that of blood in man, the degree of ionization of amobarbital in serum and saliva had to be taken into consideration. Estimation of the protein binding of amobarbital in serum from concentrations of amobarbital in saliva and serum was in good agreement with the in vitro data of equilibrium dialysis.


A double-blind randomized controlled trial to compare the safety and efficacy of dexmedetomidine alone and in combination with ketamine in uncooperative and anxious paediatric dental patients requiring pulpectomy.
To compare the sedation regimen Dexmedetomidine alone and its combination with low dose Ketamine through intravenous route in terms of safety, efficacy and recovery profile in uncooperative paediatric dental patients requiring pulpectomy. Thirty anxious and uncooperative 2-6-year-old children requiring pulpectomy in at least one primary molar were enrolled. Propofol was used as an induction agent. Drugs were administered through the intravenous route as per group assignment, i.e., Dexmedetomidine (1 µg/kg) with ketamine (0.5 mg/kg) administered over 10 min followed by a maintenance dose of Dexmedetomidine (0.2-0.8 µg/kg/h) in group A and Dexmedetomidine (1 µg/kg) administered over 10 min followed by a maintenance dose in group B. The sedation was titrated to achieve Houpt's overall behavior score of 4/5. The primary outcome measure was the successful completion of treatment. Secondary outcome measures were vital signs, quality of sedation, time need for the procedure, recovery time, intra-operative and post-operative adverse sequelae. Results showed that both of the regimens were similar in efficacy, safety and recovery profile. Also, the required dose of dexmedetomidine and the need for rescue boluses was similar in both of the study groups. Dexmedetomidine either alone or in combination with ketamine proved to be a safe and efficacious agent for paediatric dental sedation. No beneficial evidence of adding ketamine was observed.


Quiet standing postural control variables in subacute stroke: associations with gait and balance, falls prediction and responsiveness.
To examine the construct validity, predictive validity and responsiveness of standing centre of pressure variables in subacute stroke. Seventy-nine ambulatory individuals were assessed before inpatient rehabilitation discharge and three months later. Measures were: gait speed (6-metre walk), dynamic balance (step test), and quiet standing (Wii Balance Board). Centre of pressure speed, amplitude, standard deviation, root mean square, wavelet decomposition, and detrended fluctuation analysis were examined. Falls data were collected over a 12-month period post-discharge. Moderate strength correlations (r = -0.505 to -0.548) with gait speed and step test scores were shown for 3/26 centre of pressure variables (mediolateral speed, low and moderate frequency wavelet). Twenty-two participants fell and the prediction was significant for gait speed and step test (IQR-odds ratio (OR) = 4.00 & 3.21) and 3/26 centre of pressure variables (mediolateral low-frequency wavelet: IQR-OR = 2.71; mediolateral detrended fluctuation analysis: IQR-OR = 3.06; anteroposterior detrended fluctuation analysis: IQR-OR = 2.71). Significant changes over time occurred for gait speed and step test scores and 20/26 centre of pressure variables. Standing centre of pressure variables have limited validity to reflect dynamic balance and falls risk after stroke. Frequency and complexity measures warrant further exploration.Implications for rehabilitationOur findings indicate that quiet standing centre of pressure variables have limited validity to reflect dynamic balance tasks and predict falls after stroke.The mediolateral and higher frequency variables may be more strongly recommended than the commonly used total centre of pressure speed measure.Measures of signal frequency and complexity may provide insight into postural control mechanisms and how these change over time following stroke.


B7-H4, a promising target for immunotherapy.
The coinhibitory molecule B7-H4, an important member of the B7 family, is abnormally expressed in tumors, inflammation and autoimmune diseases. B7-H4 negatively regulates T cell immune response and promotes immune escape by inhibiting the proliferation, cytokine secretion, and cell cycle of T cells. Moreover, B7-H4 plays an extremely important role in tumorigenesis and tumor development including cell proliferation, invasion, metastasis, anti-apoptosis, etc. In addition, B7-H4 has the other biological functions, such as protection against type 1 diabetes (T1D) and islet cell transplantation. Therefore, B7-H4 has been identified as a novel marker or a therapeutic target for the treatment of tumors, inflammation, autoimmune diseases, and organ transplantation. Here, we summarized the expression profiles, physiological and pathological functions, and regulatory mechanisms of B7-H4, the signaling pathways involved, as well as B7-H4-based immunotherapy.


Radiological abnormalities associated with anomalies of the ninth chromosome.
The clinical and radiological features of Trisomy of the short arm of the ninth chromosome and of the Nail Patella Syndrome, both of which conditions are related to abnormalities of the ninth chromosome, are compared. Dislocation of the head of radius is seen in both conditions, as is a diminished patello condylar ratio. Several of the features described as being sporadic anomalies in the Nail Patella Syndrome are also seen in some patients with Trisomy of the Ninth Chromosome. The Trisomy 9 group also have several anomalies which are shared with Trisomy 21, Trisomy 17/18, Trisomy 13/15 and Trisomy 4, suggesting that some of these changes are a non-specific result of chromosome abnormality rather than being specific to the Trisomy 9.


SCRaMbLE-in: A Fast and Efficient Method to Diversify and Improve the Yields of Heterologous Pathways in Synthetic Yeast.
The synthetic chromosome rearrangement and modification by LoxP-mediated evolution (SCRaMbLE) system is a key component of the synthetic yeast genome (Sc2.0) project, an international effort to construct an entire synthetic genome in yeast. SCRaMbLE involves the introduction of thousands of symmetrical LoxP (LoxPsym) recombination sites downstream of every nonessential gene in all 16 chromosomes, enabling numerous genome rearrangements in the form of deletions, inversions, duplications, and translocations by the Cre-LoxPsym recombination system. We highlight a two-step protocol for SCRaMbLE-in (Liu, Nat Commun 9(1):1936, 2018), a recombinase-based combinatorial method to expedite genetic engineering and exogenous pathway optimization, using a synthetic β-carotene pathway as an example. First, an in vitro phase uses a recombinase toolkit to diversify gene expression by integrating various regulatory elements into the target pathway. This combinatorial pathway library can be transformed directly into yeast for traditional screening. Once an optimized pathway which is flanked by LoxPsym sites is identified, it is transformed into Sc2.0 yeast for the in vivo SCRaMbLE phase, where LoxPsym sites in the synthetic yeast genome and Cre recombinase catalyze massive genome rearrangements. We describe all the conditions necessary to perform SCRaMbLE and post-SCRaMbLE experiments including screening, spot test analysis, and PCRTag analysis to elucidate genotype-phenotype relationships.


[Slow transit constipation treated by surgery: analysis of 17 cases].
To explore the operative indications, prognosis, and possible pathogenic factors of slow transit constipation (STC). 17 cases with STC who had undergone colectomy were analysed. Bowel movement frequency was once per 4 to 14 days in all of the patients, who had had long-term laxative abuse. Delayed colonic transit was demonstrated in all patients, 82.4% of them were accompanied by outlet obstructive constipation (OOC) and 50% showed abnormal sex hormones. Reduced numbers of argyrophilic neurons and vacuolar degeneration of axons were demonstrated at the myenteric plexus pathologically. Three patients had adhesive ileus postoperatively and one patient suffered from difficult evacuation again 5 years after the operation. Colectomy is highly effective in alleviating symptoms in patients with STC, and pelvic floor disorder of OOC should be treated simultaneously.


Mitoepigenetics: An intriguing regulatory layer in aging and metabolic-related diseases.
As a key organelle in eukaryotic cells, mitochondria play a central role in maintaining normal cellular functions. Mitochondrial dysfunction is reported to be closely related with aging and various diseases. Epigenetic modifications in nuclear genome provide a substantial layer for the modulation of nuclear-encoded gene expression. However, whether mitochondria could also be subjected to such similar epigenetic alterations and the involved mechanisms remain largely obscure and controversial. Recently, accumulating evidence has suggested that mitochondrial epigenetics, also known as mitoepigenetics may serve as an intriguing regulatory layer in mitochondrial DNA (mtDNA)-encoded gene expression. Given the potential regulatory role of mitoepigenetics, mitochondrial dysfunction derived from mitoepigenetics-induced abnormal gene expression could also be closely associated with aging and disease development. In this review, we summarized the recent advances in mitoepigenetics, with a special focus on mtDNA methylation in aging and metabolic-related diseases as well as the new methods and technologies for the study of mitoepigenetics. Uncovering the regulatory role of mitoepigenetics will help to understand the underlying mechanisms of mitochondrial dysfunction and provide novel strategies for delaying aging and preventing metabolic-related diseases.


Computed tomography detection of transplant renal artery pseudoaneurysm.
Clinically unsuspected pseudoaneurysm formation of the arterial anastomosis in a patient with a renal transplant was initially diagnosed by computed tomography. This rare but serious complication can also be detected by ultrasound or radionuclide flow study, as shown in our patient. An awareness of this lesion and familiarity with its appearance can permit its early detection before exsanguinating hemorrhage occurs.


Nutrient regeneration in coastal seas by Noctiluca scintillans, a red tide-causing dinoflagellate.
Ammonium nitrogen, phosphate, and silicate contents in Noctiluca scintillans cell fluid were estimated at 2470, 183, and 54 pmol per individual, respectively. Ammonium nitrogen and phosphate concentrations at the surface layer of the water column seemed to be related to cell abundance of N. scintillans at the sampling location. Patches of N. scintillans provided 16 and 25 times greater concentrations of ammonium nitrogen and phosphate in the uppermost layer (0-10 cm depth) of the water column than those in the ambient seawater, respectively. Silicate concentration within patches, however, was close to that in surrounding water. The morphology of fecal pellets of N. scintillans fed on the diatom, Thalassiosira sp., was examined with a scanning electron microscope. The fecal pellet was composed entirely of visible structural diatom cells. It could be inferred that N. scintillans excretes silica from the diatom undigested in its fecal pellets and thus no remarkably high silicate concentration within red tide patches was observed.


Composite tissue (limb) allografts in rats. II. Indefinite survival using low-dose cyclosporine.
Cyclosporine has reawakened interest in transplantation of peripheral composite tissue allografts (CTA) of skin, muscle, bone, vessel, and nerves. The purpose of this study was to examine whether cyclosporine could produce indefinite survival of CTA. Two groups of LEW recipients of LBN limb transplants were given different long-term treatments of cyclosporine. Tolerance was achieved in many of the animals. Several possibilities for the mechanism of this tolerance are discussed.


Posterior urethral trauma and strictures: an attempt to solve a controversy.
Three cases of traumatic partial or complete posterior urethral rupture and subsequent stricture are reported. Treatment consisted of early suprapubic cystostomy, with/or without concomitant primary realignment of the urethra over a catheter, followed by urethral dilations and internal urethrotomy when indicated. Followup of 4 or more years showed excellent results.


ZnCl2 modified biochar derived from aerobic granular sludge for developed microporosity and enhanced adsorption to tetracycline.
In this study, biochar derived from aerobic granular sludge was modified by ZnCl2 (Zn-BC) to improve the adsorption performance of tetracycline (TC). The surface area, pores, and functional groups of Zn-BC were characterized by scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) surface area, Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) and the effects of initial pH, TC concentration, and temperature on TC adsorption performance were analyzed. At the same time, the adsorption kinetics, isotherms, thermodynamics and diffusion models were studied. The results showed that the BET surface area and micropore volume of Zn-BC were 852.41 m2·g-1 and 0.086 cm3·g-1, respectively. The maximum adsorption performance of TC was 93.44 mg·g-1, and it was less influenced by pH. The adsorption of TC on Zn-BC agreed well with the pseudo-second-order model and the Langmuir isotherm. The thermodynamic parameters indicated that the adsorption process was a spontaneously endothermic reaction.


Loss of doctor-to-doctor communication: lessons from the reconfiguration of mental health services in England.
To explore the tensions across the primary-secondary interface when referral from primary care is to a team and to inform service developments in other specialties. A nested qualitative study within a randomized controlled trial of primary care and Community Mental Health Teams (CMHTs) in Croydon and Manchester, UK. For the qualitative study, interviews were carried out with general practitioners (GPs), psychiatrists and managers or clinical leads of the CMHTs. GPs described the need for access to specialist knowledge, which they perceived to lie with the psychiatrist, and referral to a team was not perceived to allow this access. A personal threshold was identified by GPs after which they referred the patient to secondary care. CMHTs and psychiatrists recognized that this personal threshold differed between GPs, but their criteria for accepting referrals did not seem to allow for a flexible response to referral requests, leading to the referral being labelled as 'inappropriate'. The lack of direct doctor-to-doctor communication was perceived by respondents to contribute to a fragmentation of patient care. Strategies were described whereby the system was bypassed to achieve doctor-to-doctor communication, which undermined the team. Development of intermediate or 'Tier 2' services beyond the mental health services, where the GP refers to a team rather than to a specialist (hospital consultant) could benefit from reflecting on experiences with mental health services. There is a danger that new community services for the physically ill will engender the same level of confusion and discontent described by GPs and other health professionals in this study who are concerned with mental health care. Flexibility is needed within care pathways, including the provision of direct doctor-to-doctor communication together with approaches to minimize the marginalization of non-medical professionals.


Targeting angiopoietin-2 signaling in cancer therapy.
Over the past decade, several anti-angiogenic strategies have been devised to target a wide spectrum of malignancies. The most widely utilized approach involves abrogation of vascular endothelial growth factor receptor signaling through either consumption of ligand (i.e., with the monoclonal antibody bevacizumab) or through direct inhibition of the receptor tyrosine kinase domain (i.e., with small molecules such as sunitinib or sorafenib). While these agents do appear to delay cancer progression in the clinic, they are not curative approaches. A novel anti-angiogenic strategy involves inhibition of signaling along the Ang/Tie-2 axis, a pathway critical for mediating endothelial and perivascular cell interactions. While several agents (i.e., AMG-386 and regorafenib) have reached late stages of clinical development, others (i.e., ARRY614 and CEP-11981) are in their relative infancy. Herein, we will outline the clinical trajectory of wide spectrum Ang/Tie-2 inhibitors, with attention to data evaluating combinations with cytotoxic therapy or other targeted agents. Provided that these approaches to not drastically augment toxicity, they may represent the ideal path for further development of this class of agents.


An epidemiological assessment of choking-induced out-of-hospital cardiac arrest: A post hoc analysis of the SOS-KANTO 2012 study.
The aim of this study was to reveal the neurological outcomes of choking-induced out-of-hospital cardiac arrest (OHCA) and evaluate the presence of witnesses, cardiopulmonary resuscitation (CPR) performed by a witness (bystander-witnessed CPR), and the proportion of patients with favourable neurological outcomes by the time from CPR by emergency medical services (EMS) to the return of spontaneous circulation (ROSC) (CPR-ROSC time). We retrospectively analysed the SOS-KANTO 2012 database, which included data of 16,452 OHCAs in Japan. We selected choking-induced OHCA patients aged ≥ 20 years. We evaluated the neurological outcomes at 1 month with the Cerebral Performance Category (CPC). We defined favourable neurological outcomes (CPCs: 1-2) and present the outcomes with descriptive statistics. Of 1,045 choking-induced OHCA patients, 18 (1.7%) had a favourable neurological outcome. Of 1,045 OHCAs, 757 (72.6%) were witnessed, and 375 (36.0%) underwent bystander-witnessed CPR. Of the 18 OHCAs with favourable outcomes, 17 (94.4%) were witnessed, and 11 (61.1%) underwent bystander-witnessed CPR. With a CPR-ROSC time of 0-5 minutes, the proportion of patients with favourable neurological outcomes was 29.7%, ranging from 0% to 6% in the following time groups. The neurological outcome of choking-induced OHCA was poor. The neurological outcomes deteriorated rapidly from 5 minutes after the initiation of CPR by EMS. The presence of witnesses and bystander-witnessed CPR may be factors that contribute to improved outcomes, but the effects were not remarkable. As another approach to reduce deaths due to choking, citizen education for the prevention of choking may be effective.


Gestational diabetes mellitus and its impact on the mother-infant relationship: A cohort study in the postnatal period.
Women with gestational diabetes mellitus (GDM) are at increased risk of poor perinatal mental health outcomes. However, the association between GDM and the mother-infant relationship is unclear. This study aimed to examine whether GDM itself impacts the mother-infant relationship and maternal mental health using a cohort study design. We used data from the Cohort of Newborns in Emilia-Romagna (CoNER) study, which included 642 women recruited in Bologna, Italy. Psychological data were collected at 6 and 15 months postnatally using a purpose designed measure to examine the mother-infant relationship. We used linear fixed effects and mixed-effects models to assess the effect of GDM on relationship scores at 6 and 15 months postpartum. Women with GDM had significantly lower relationship scores at 15 months postpartum [β - 1.75 95% CrI (-3.31; -0.21)] but not at 6 months [β - 0.27 95% CrI (-1.37; 0.81)]. Mother-infant relationship scores were significantly lower overall at 15 months compared to 6 months postpartum [β - 0.29 95% CrI (-0.56; -0.02)]. Our findings suggest that there may be a delayed effect on the mother-infant relationship in response to the experience of GDM. Future research using large birth cohorts should investigate this further to confirm these findings, and whether women with GDM would benefit from early interventions to improve relationships taking into account length of time postpartum.


Influence of cell-model boundary conditions on the conductivity and electrophoretic mobility of concentrated suspensions.
In the last few years, different theoretical models and analytical approximations have been developed addressing the problem of the electrical conductivity of a concentrated colloidal suspension. Most of them are based on the cell model concept, and coincide in using Kuwabara's hydrodynamic boundary conditions, but there are different possible approaches to the electrostatic boundary conditions. We will call them Levine-Neale's (LN, they are Neumann type, that is they specify the gradient of the electrical potential at the boundary), and Shilov-Zharkikh's (SZ, Dirichlet type). The important point in our paper is that we show by direct numerical calculation that both approaches lead to identical evaluations of the conductivity of the suspensions if each of them is associated to its corresponding evaluation of the macroscopic electric field. The same agreement between the two calculations is reached for the case of electrophoretic mobility. Interestingly, there is no way to reach such identity if two possible choices are considered for the boundary conditions imposed to the field-induced perturbations in ionic concentrations on the cell boundary (r = b), deltan(i) (r = b). It is demonstrated that the conditions deltan(i)(b) = 0 lead to consistently larger conductivities and mobilities. A qualitative explanation is offered to this fact, based on the plausibility of counter-ion diffusion fluxes favoring both the electrical conduction and the motion of the particles.


Hemodynamic and metabolic responses to leukotriene C4 in isolated perfused rat liver.
Responses of isolated perfused rat liver to leukotriene C4 were studied in order to assess the mechanisms involved in leukotriene-mediated liver injury. Infusion of leukotriene C4 (11 and 44 pmoles per min per gm liver weight) into the portal vein resulted in a rise in portal pressure, a decrease in oxygen consumption, an increase in hepatic glucose and lactate efflux and lactate/pyruvate ratio in the perfusate and a small decrease in bile flow. Isoproterenol (1 microM) counteracted the effects of leukotriene C4 on respiration and portal pressure, whereas bile flow and glucose efflux were reversibly stimulated. The same changes were observed upon withdrawal of leukotriene C4. The release of glucose was correlated with the increase in oxygen consumption upon both isoproterenol addition and withdrawal of leukotriene C4. These results are indicative of leukotriene C4-induced microcirculatory redistribution of perfusate flow. Since, in the presence of nitroprusside (50 microM), both the effects of leukotriene C4 and their reversal by isoproterenol were diminished, a vascular site of action can be assumed. Accordingly, the accompanying metabolic responses can be explained by gradual changes in oxygen supply to parts of the liver. Reversibility of the leukotriene C4 effects and lack of short-term impairment of viability of the isolated liver suggest that leukotriene-mediated liver injury is a long-term effect related to events subsequent to microcirculatory changes.


Detrimental effects of a failed infection by a co-invasive parasite on a native congeneric parasite and its native host.
Biological invaders often are accompanied by co-invasive parasites that can alter ecosystem function and established native host-parasite relationships. When these co-invasive parasites establish in a community, they can affect native host fitness and native parasite infection intensity, prevalence, and success within the native host. The mosquito, Aedes triseriatus, is North American host to protozoan parasite, Ascogregarina barretti. In geographic regions invaded by the mosquito Aedes albopictus, A. triseriatus may also be infected by A. albopictus' co-invasive parasite, Ascogregarina taiwanensis. We tested the hypotheses that: 1) The presence of a co-invasive parasite will negatively affect native parasite fitness, yielding decreased infection intensity, prevalence, and infection success, which could be caused by immune induction of the host or inter-parasite competition, and 2) Coinfection with the native and co-invasive parasites will negatively affect host fitness, yielding increased larval development time and decreased survival and reproductive fitness, caused by increased costs of infection. In our coinfection experiments we find that any exposure to the co-invasive parasite resulted in decreased survivorship and increased development time of the host A. triseriatus, with or without coinfection by the native parasite. Exposure to both co-invasive and native parasites yielded reduced native parasite infection intensity in the host larva and reduced native parasite propagule production in the resulting male adults. Together, these results indicate not only the potential for the co-invasive parasite to alter the native host-parasite relationship, but to impact native host population dynamics.


A rare syndrome that can easily be missed: May-Hegglin anomaly.
May-Hegglin is a rare disease characterized by macrothrombocytopenia and presence of Döhle-like bodies in white cells. We present a patient treated with acute myeloid leukemia had pale-blue colored inclusion bodies assuming Döhle in his neutrophils.


[Defects in the prostaglandin system. I. Familial total plasma factor deficiency].
A case of a 38 year-old male is reported, in whom routine general investigation after myocardial infarction revealed a deficiency in the prostacyclin synthesis stimulating plasma factor. Examination of all available members of the family showed a congenital defect of as yet unknown pathogenetic significance.


[Ischemia-reperfusion injury during experimental heart transplantation. Evaluation of trimetazidine's cytoprotective effect].
The objectives of this study were to analyze the ischemia-reperfusion injury due to free radicals that occurs during heart transplantation and to determine the potential cytoprotective effect of trimetazidine. A total of 21 orthotopic heart transplantations were performed in pigs. We divided the experimental animals into 2 groups: in group A (n=11),standard myocardial protection was used; in group B (n=10), trimetazidine was added to the cardioplegic solution used to protect the donor heart and to the solution administered to the recipient prior to release of the aortic clamp (trimetazidine, 10(-5) mol/L), and recipients were pretreated with trimetazidine, 2.5 mg/kg. Blood samples were taken from the recipients coronary sinus at three times: at baseline, during ischemia, and during reperfusion. We measured the levels of malondialdehyde, a marker of lipid peroxidation, and of several antioxidants: glutathione peroxidase, glutathione reductase, superoxide dismutase, alpha-tocopherol, and retinol. The total antioxidant status was also determined. Malondialdehyde production and enzymatic antioxidant activity rose during ischemia and reperfusion, while the retinol level decreased. The increases in malondialdehyde level and glutathione peroxidase activity that occurred between baseline and reperfusion were significantly higher in group A. CONCLUSIONS. The degree of lipid peroxidation and the level of activity of intracellular antioxidant mechanisms increased progressively throughout transplantation. Trimetazidine had a cytoprotective effect. It ameliorated free radical-induced reperfusion injury and modified the response pattern of several defense mechanisms.


Relative contribution of food and water to 27 metals and metalloids accumulated by caged Hyalella azteca in two rivers affected by metal mining.
Hyalella were caged at three sites in each of the two rivers for 17 days. Food added to the cages consisted of plant and detrital material collected from the same, or other, sites. Concentrations of some metals in Hyalella (e.g., Cd and Cu), but not others (e.g., Se), appeared to reach steady-state within 5 days in one of the rivers. Metal accumulation was minimal by day 5 in the other river, possibly due to the very low temperatures in this river for the first part of the exposure period. Both analysis of variance and analysis of covariance, using site as a categorical variable and metal in food as either a categorical or continuous variable, indicated that Cd, Cu and Se were the only metals for which concentration in food had a significant effect on concentration in Hyalella. Nevertheless, water was still a major source for these metals as well. Other metals which varied by over fivefold in food but for which concentration in food had no effect on concentration in Hyalella included Ag, As, Bi, Sb, U and Zn. Concentrations of the remaining metals varied less than fourfold in food, making it difficult to determine if these were accumulated from food.


[Inhibition of cellular signal transduction cascades. A future anti-invasive therapeutic strategy for cancers of the head and neck region].
Squamous cell carcinomas of the head and neck are considered to be highly aggressive cancers. The 5-year survival rate of patients with this disease depends on whether a locoregional relapse occurs and if so, how early after the initial treatment. Disease was found to relapse more frequently in patients suffering from cancers with an invasive growth pattern. It was therefore concluded that cancer cell invasion influences the patient's survival. While considerable efforts are made to develop treatment regimens for relapsing disease, a novel approach consists of the prevention of the disease recurrence through the inhibition of cancer cell invasion. Literature search. We summarize in this article the mechanisms of tumor invasion, focusing on the regulation of tumor proteases, which are essential for cancer invasion, and provide an overview of preliminary results with novel anti-invasive treatment strategies. Novel anti-invasive treatment regimens based on an understanding of molecular cancer invasion mechanisms may be used in the future to treat patients with head and neck cancers.


The absolute granulocyte count in ascites fluid. An aid to the diagnosis of spontaneous bacterial peritonitis.
The absolute granulocyte count of peritoneal fluid was determined for 98 consecutive patients with ascites in order to assess its value as an early indication of bacterial infection. The absolute granulocyte count was found to be more sensitive and specific than either the total leukocyte count or differential count alone. When the absolute granulocyte count in ascites fluid is greater than 250 per cu mm, then it is likely that infection is present.


A statistical procedure for the analysis of microbial communities based on phenotypic properties of isolates.
A novel statistical procedure for the analysis of microbial communities based on phenotypic properties of randomly collected isolates is presented and discussed. The procedure allows the representation of the microbial communities as a set of ellipses in a bidimensional graph. This representation is obtained by the following steps: (a) measurement of a set of binary phenotypic properties for n isolates belonging to k samples, each representing a different community; (b) repeated sampling by bootstrapping of the m samples, thus obtaining, for each community, i subsamples of j isolates; (c) calculation of the frequency of positive results for each test for each subsample; (d) calculation of the matrix of Euclidean distances between the k x i frequency vectors; (e) use of multidimensional scaling (MDS) to obtain a representation in two dimensions of the distance relationships between the frequency vectors; (f) plotting of the 95% confidence ellipses for the i frequency vectors of each of the k communities. By using both simple, synthetic microbial communities, and samples of lactic acid bacteria isolated from natural microbial communities (sourdoughs, compressed yeast, fermented sausages), it was demonstrated that the position and shape of the ellipses are clearly related to the composition of the community, while the relationship between the size of the ellipses and the phenotypical diversity of the community is less straightforward: while communities with very different diversity (measured with the Functional Evenness index and the mean taxonomic distance) had ellipses that were very different in size, there was no strict proportionality between the size of the ellipse and the diversity of the community. Nevertheless, the representation of microbial communities obtained by bootstrapping and multidimensional scaling appears to be superior to the more usual representation based on tabulation of the frequencies of isolates belonging to different clusters.


Structure determination of a monoclonal Fab fragment specific for histidine-containing protein of the phosphoenolpyruvate: sugar phosphotransferase system of Escherichia coli.
Jel 42 is a monoclonal antibody specific for histidine-containing protein, a small phosphocarrier protein required for sugar transport in Escherichia coli. Fab fragments prepared from this antibody by papain digestion consisted of three major isoelectric forms which were separated on a chromatofocusing column. Two of these forms produced large crystals in space group P21 and unit cell dimensions a = 117.48 A, b = 66.56 A, c = 67.31 A, and beta = 118.7 degrees, with two Fab fragments per asymmetric unit. Data were collected to 3.5-A resolution. The structure of Fab Jel 42 was solved by the Molecular Replacement method (least-squares refined to R = 0.282) using the known structure of Fab HED 10 (12) as the search model; the amino acid residues of the hypervariable and elbow regions of Fab HED 10 were omitted from the starting model. A Fourier map calculated at this stage revealed electron density which corresponded to the hypervariable loops forming the antigen-binding crevice and the elbow region of Fab Jel 42. The elbow angles for the two independent Fab molecules are 159 and 167 degrees, similar to that of the Fab HED 10 search model which has an elbow angle of 162 degrees. There is no local noncrystallographic axis of symmetry relating the two molecules in the asymmetric unit.


Clinical findings and adverse outcome in neonates with symptomatic congenital cytomegalovirus (SCCMV) infection.
Congenital cytomegalovirus (CCMV) infection is a common neonatal infection affecting 1% of all live births, 10% of which are symptomatic. Many of these infants have long-term sequelae. The objective is to document the clinical presentation of SCCMV infection in neonates, the frequency of sequelae and severity of adverse neurologic outcomes and risk factors. A review and analysis of all symptomatic infants diagnosed with SCCMV infection are given. SCCMV was defined as a diagnosis of CCMV infection in the first three weeks of life in the presence of any clinical manifestations. Outcome data from 2 years of age and later are analyzed. There were 104 patients identified as having SCCMV infection and of these 42 cases had definite infection. The common findings at presentation were hepatosplenomegaly 19/42 (45%), thrombocytopenia 21/42 (50%), elevated transaminases 21/42(50%), abnormal cranial US scan 24/41(56%), abnormal head CT scan 29/41(71%) and abnormal brain MRI 17/19(89%). The risk factors for an adverse outcome including death or deafness or blindness or moderate to severe neurological deficits included an abnormal cranial US scan (OR 8.5), abnormal head CT scan (OR 21) and abnormal brainstem auditory evoked responses (BAER) (OR 8.7). There was only three (7%) patients without any deficits and severely affected infants have been identified with a diverse clinical presentation, reinforcing the importance of CMV as a major public health problem.


Remote sensing of the xanthophyll cycle and chlorophyll fluorescence in sunflower leaves and canopies.
Sudden illumination of sunflower (Helianthus annuus L. cv. CGL 208) leaves and canopies led to excess absorbed PFD and induced apparent reflectance changes in the green, red and near-infrared detectable with a remote spectroradiometer. The green shift, centered near 531 nm, was caused by reflectance changes associated with the de-epoxidation of violaxanthin to zeaxanthin via antheraxanthin and with the chloroplast thylakoid pH gradient. The red (685 nm) and near-infrared (738 nm) signals were due to quenching of chlorophyll fluorescence. Remote sensing of shifts in these spectral regions provides non-destructive information on in situ photosynthetic performance and could lead to improved techniques for remote sensing of canopy photosynthesis.


Comparison of fetal and maternal tissue elasticity between euploid and aneuploid pregnancies by shear wave elastography.
B-mode ultrasonography utilized for fetal screening of common trisomies is referred to as a genetic sonogram and includes determining major abnormalities and soft markers such as hypoplastic nasal bone and increased thickness of the nuchal fold. Elastography is a novel ultrasound technique giving information about tissue stiffness used for diagnosing cancer, transplant rejection, and organ fibrosis. This study aimed to determine via shear wave elastography (SWE) whether euploid and aneuploid fetal soft marker tissues vary in stiffness. The participants were all singleton pregnancies between 19 and 23 weeks of gestation; 35 euploid and 14 aneuploid fetus pregnancies were enrolled. Fetal bowel, kidney, liver, nasal bone, nuchal fold, placenta, and myometrium were investigated with SWE using acoustic radiation impulse force. Images were analyzed with a novel software calibrated and written by us using MATLAB. Statistical analysis was completed with the SPSS Program. Shapiro-Wilk normality distribution analysis, Student's t-test, and Mann-Whitney U methods were used. The mean shear wave speed of fetal nasal bone was significantly lower in aneuploid fetuses. There was no difference between other tissues in mean shear wave velocity. Euploid and aneuploid fetuses have different elastic properties of the nasal bone and this may have a role in differentiating aneuploid fetuses noninvasively.


Medical student self-efficacy with family-centered care during bedside rounds.
Factors that support self-efficacy in family-centered care (FCC) must be understood in order to foster FCC in trainees. Using social cognitive theory, the authors examined (1) how three supportive experiences (observing role models, practicing for mastery, and receiving feedback) influence self-efficacy with FCC during rounds and (2) whether the influence of these supportive experiences was mediated by self-efficacy with three key FCC tasks (relationship building, information exchange, and decision making). Researchers surveyed third-year students during pediatric clerkship rotations during the 2008-2011 academic years. Surveys assessed supportive experiences and students' self-efficacy both with FCC during rounds and with key FCC tasks. Researchers constructed measurement models via exploratory and confirmatory factor analyses. Composite indicator structural equation models evaluated whether supportive experiences influenced self-efficacy with FCC during rounds and whether self-efficacy with key FCC tasks mediated any such influences. Of 184 eligible students, 172 (93%) completed preclerkship surveys. Observing role models and practicing for mastery supported self-efficacy with FCC during rounds (each P < .01), whereas receiving feedback did not. Self-efficacy with two specific FCC tasks-relationship building and decision making (each P < .05)-mediated the effects of these two supportive experiences on self-efficacy with FCC during rounds. Both observing role models and practicing for mastery foster students' self-efficacy with FCC during rounds, operating through self-efficacy with key FCC tasks. Results suggest the importance both of helping students gain self-efficacy in key FCC tasks before rounds and of helping educators implement supportive experiences during rounds.


Validating the anti-lymphoma pharmacodynamic actions of the endocannabinoids on canine non-Hodgkin lymphoma.
This study established the in vitro anti-lymphoma pharmacodynamic actions of the endocannabinoids (anandamide-AEA and 2-arachidonoylglycerol-2AG) on canine non-Hodgkin lymphoma (NHL) and human NHL cells. The expression of cannabinoid (CB1 and CB2) receptors in various canine NHL cells {1771, CLBL-1, CLL-1, peripheral blood mononuclear cells (PBMCs)} was studied using Quantitative real-time PCR (RT-qPCR). Anti-lymphoma cell viability assay was performed to assess the effect of endocannabinoids on various canine and human NHL cells (1771, CLBL-1, CLL-1, Ramos cells). The spectrophotometric and fluorometric procedures evaluated oxidative stress, inflammation, apoptosis, and mitochondrial function markers. SAS® and Prism-V La Jolla, CA, USA, were used for statistical analysis. The current study validated the presence of CB1 and CB2 receptors in the canine NHL cells. There was a significantly higher expression of CB1 and CB2 receptors in B-cell lymphoma (BCL) cells (1771, CLBL-1, Ramos) compared to canine T-cell lymphoma (TCL) cells (CL-1). AEA and 2AG dose and time-dependently exhibited significant but differential anti-lymphoma effects on canine and human NHL cells. Anti-lymphoma pharmacodynamic actions of the endocannabinoids in the canine 1771 NHL cells revealed a significant alteration in the markers of oxidative stress, inflammation, and a decrease in mitochondrial function without altering the apoptotic markers. Establishing the anti-lymphoma pharmacodynamic actions of endocannabinoids may provide new therapeutic interventions and expedite cannabinoid research.


Spinal epidural lipomatosis--a brief review.
Spinal epidural lipomatosis (SEL) is a rare disorder characterized by overgrowth of fat in the extradural space, causing compression of the neural elements. It is frequently associated with the administration of exogenous steroids or elevation of endogenous steroids. We present two patients, both with epidural lipamotosis of idiopathic origin. One was 53-year-old man with progressive mid-thoracic and lower limb pain with associated weakness and neurogenic claudication due to thoracic epidural lipomatosis. The second was a 68-year-old male with lumbar epidural lipomatosis. Co-morbidities for the first patient included diabetes and obesity; however, there was no history of steroid administration. An MRI scan revealed thoracic cord compression, with significant stenosis at T4-T9. The second patient complained of progression of longstanding lumbar pain and claudicant symptoms. There was no history of steroid intake. An MRI revealed stenosis at L4-S1 and diffuse anterior lipomatosis. A literature review revealed 49 cases of idiopathic SEL and 62 of secondary SEL. We aimed to delineate the differences between these two relatively distinct entities including their anatomical distribution, clinical presentation and prognostic implications.


Effects of pioglitazone and rosiglitazone on blood lipid levels and glycemic control in patients with type 2 diabetes mellitus: a retrospective review of randomly selected medical records.
The antihyperglycemic effects of pioglitazone hydrochloride and rosiglitazone maleate are well documented. The results of clinical trials and observational studies have suggested, however, that there are individual differences in the effects of these drugs on blood lipid levels. The present study evaluated the effects of pioglitazone and rosiglitazone on blood lipid levels and glycemic control in patients with type 2 diabetes mellitus. This was a retrospective review of randomly selected medical records from 605 primary care practices in the United States in which adults with type 2 diabetes received pioglitazone or rosiglitazone between August 1, 1999, and August 31, 2000. The outcome measures were mean changes in serum concentrations of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and glycosylated hemoglobin (HbA1c) values. Treatment with pioglitazone was associated with a reduction in mean TG of 55.17 mg/dL, a reduction in TC of 8.45 mg/dL, an increase in HDL-C of 2.65 mg/dL, and a reduction in LDL-C of 5.05 mg/dL. Treatment with rosiglitazone was associated with a reduction in mean TG of 13.34 mg/dL, an increase in TC of 4.81 mg/dL, a reduction in HDL-C of 0.12 mg/dL, and an increase in LDL-C of 3.56 mg/dL. With the exception of HDL-C, the differences in mean changes in lipid parameters between treatment groups were statistically significant (P < 0.001, pioglitazone vs rosiglitazone). Reductions in HbA1c were statistically equivalent between treatments (1.04% pioglitazone, 1.18% rosiglitazone). Treatment with pioglitazone was associated with greater beneficial effects on blood lipid levels than treatment with rosiglitazone, whereas glycemic control was equivalent between the 2 treatments.


Noncemented, porous ingrowth knee prosthesis: the 3- to 8-year results.
To determine the principal long-term problems encountered in noncemented total knee replacement. A cohort of 252 consecutive cases of total knee replacement with no exclusions. Follow-up ranged from 3 to 8 years. A university-affiliated institution specializing in orthopedic surgery. All 252 patients had arthritis of the knee, mainly osteoarthritis. All agreed preoperatively to prolonged postoperative follow-up. Noncemented total knee replacement with the Tricon M prosthesis, which has a metal-backed patella. The Hospital for Special Surgery rating system for clinical results and the radiologic results, including reasons for revision surgery. Thirty-five prostheses were revised: 11 prostheses because of patellar wear only; in 13 prostheses the tibial component (mainly a 6-mm unit) and patella were revised because of wear; 6 prostheses were revised for sepsis, 4 for reflex sympathetic dystrophy and 1 only for sinkage of the tibial component. Of the remaining 217 prostheses, 88% scored good or excellent, 6% fair and 6% poor. The single most common cause of failure was polyethylene wear. This was associated with the metal backing of the patella and the use of thin, polyethylene tibial components.


Oral Microbiota, Bacterial Infections, Antibiotic Prescriptions, and Antimicrobial Resistance in Children.
The oral cavity hosts the second most diverse microbial community, over 700 bacterial taxa, with the human gut having the widest diversity [...].


Out of our reach? Assessing the impact of introducing a critical care outreach service.
An outreach service was introduced in three surgical wards and the surgical high dependency unit in a large teaching hospital. A modified early warning score and callout algorithm were used to facilitate referrals to the team. Changes in unplanned admission rate to intensive care, length of stay, mortality rate and number of re-admissions following the introduction of outreach were sought. Following the introduction of the outreach service the emergency admission rate to intensive care fell from 58% to 43% (p = 0.05). These emergency patients had shorter lengths of stay (4.8 days vs. 7.4 days) and had a lower mortality (28.6% vs. 23.5%, p = 0.05). The re-admission rate also fell from 5.1% to 3.3% (p = 0.05). The outreach service had a significant impact on critical care utilisation.


Systems analysis of methylerythritol-phosphate pathway flux in E. coli: insights into the role of oxidative stress and the validity of lycopene as an isoprenoid reporter metabolite.
High-throughput screening methods assume that the output measured is representative of changes in metabolic flux toward the desired product and is not affected by secondary phenotypes. However, metabolic engineering can result in unintended phenotypes that may go unnoticed in initial screening. The red pigment lycopene, a carotenoid with antioxidant properties, has been used as a reporter of isoprenoid pathway flux in metabolic engineering for over a decade. Lycopene production is known to vary between wild-type Escherichia coli hosts, but the reasons behind this variation have never been fully elucidated. In an examination of six E. coli strains we observed that strains also differ in their capacity for increased lycopene production in response to metabolic engineering. A combination of genetic complementation, quantitative SWATH proteomics, and biochemical analysis in closely-related strains was used to examine the mechanistic reasons for variation in lycopene accumulation. This study revealed that rpoS, a gene previously identified in lycopene production association studies, exerts its effect on lycopene accumulation not through modulation of pathway flux, but through alteration of cellular oxidative status. Specifically, absence of rpoS results in increased accumulation of reactive oxygen species during late log and stationary phases. This change in cellular redox has no effect on isoprenoid pathway flux, despite the presence of oxygen-sensitive iron-sulphur cluster enzymes and the heavy redox requirements of the methylerythritol phosphate pathway. Instead, decreased cellular lycopene in the ΔrpoS strain is caused by degradation of lycopene in the presence of excess reactive oxygen species. Our results demonstrate that lycopene is not a reliable indicator of isoprenoid pathway flux in the presence of oxidative stress, and suggest that caution should be exercised when using lycopene as a screening tool in genome-wide metabolic engineering studies. More extensive use of systems biology for strain analysis will help elucidate such unpredictable side-effects in metabolic engineering projects.


Mesothelial Cells Participate in Endometriosis Fibrogenesis Through Platelet-Induced Mesothelial-Mesenchymal Transition.
While fibrosis in endometriosis has recently loomed prominently, the sources of myofibroblasts, the principal effector cell in fibrotic diseases, remain largely obscure. Mesothelial cells (MCs) can be converted into myofibroblasts through mesothelial-mesenchymal transition (MMT) in many fibrotic diseases and adhesion. To evaluate whether MCs contribute to the progression and fibrogenesis in endometriosis through MMT. Dual immunofluorescence staining and immunohistochemistry using antibodies against calretinin, Wilms' tumor-1 (WT-1), and α-smooth muscle actin (α-SMA) were performed on lesion samples from 30 patients each with ovarian endometrioma (OE) and deep endometriosis (DE), and 30 normal endometrial (NE) tissue samples. Human pleural and peritoneal MCs were co-cultured with activated platelets or control medium with and without neutralization of transforming growth factor β1 (TGF-β1) and/or platelet-derived growth factor receptor (PDGFR) and their morphology, proliferation, and expression levels of genes and proteins known to be involved in MMT were evaluated, along with their migratory and invasive propensity, contractility, and collagen production. The number of calretinin/WT-1 and α-SMA dual-positive fibroblasts in OE/DE lesions was significantly higher than NE samples. The extent of lesional fibrosis correlated positively with the lesional α-SMA staining levels. Human MCs co-cultured with activated platelets acquire a morphology suggestive of MMT, concomitant with increased proliferation, loss of calretinin expression, and marked increase in expression of mesenchymal markers. These changes coincided with functional differentiation as reflected by increased migratory and invasive capacity, contractility, and collagen production. Neutralization of TGF-β1 and PDGFR signaling abolished platelet-induced MMT in MCs. MCs contribute to lesional progression and fibrosis through platelet-induced MMT.


Association of internet use and depression among the spinal cord injury population.
To examine the relation between the frequency of Internet use and depression among people with spinal cord injury (SCI). Cross-sectional survey. SCI Model Systems. People with SCI (N=4618) who were interviewed between 2004 and 2010. Not applicable. The frequency of Internet use and the severity of depressive symptoms were measured simultaneously by interview. Internet use was reported as daily, weekly, monthly, or none. The depressive symptoms were measured by the Patient Health Questionnaire-9 (PHQ-9), with 2 published criteria being used to screen for depressive disorder. The diagnostic method places more weight on nonsomatic items (ie, items 1, 2, and 9), and the cut-off method that determines depression by a (PHQ-9) score ≥10 places more weight on somatic factors. The average scores of somatic and nonsomatic items represented the severity of somatic and nonsomatic symptoms, respectively. Our multivariate logistic regression model indicated that daily Internet users were less likely to have depressive symptoms (odds ratio=.77; 95% confidence interval, .64-.93), if the diagnostic method was used. The linear multivariate regression analysis indicated that daily and weekly Internet usage were associated with fewer nonsomatic symptoms; no significant association was observed between daily or weekly Internet usage and somatic symptoms. People with SCI who used the Internet daily were less likely to have depressive symptoms.


Prenatal and childhood exposure to poly- and perfluoroalkyl substances (PFAS) and cognitive development in children at age 8 years.
Toxicological studies indicate that poly- and perfluoroalkyl substances (PFAS) may be neurotoxic, but human studies have yet to provide compelling evidence for PFAS' impact on cognitive abilities. To test whether prenatal and childhood PFAS are associated with cognitive abilities at 8 years and whether sex modifies these associations. We included 221 mother-child pairs from the Health Outcomes and Measures of the Environment (HOME) Study, a birth cohort in Cincinnati, OH (USA). We quantified PFAS in maternal serum at 16 ± 3 weeks gestation and in child serum at 3 and 8 years. We used the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) at age 8 years, assessing Full Scale IQ (FSIQ), verbal comprehension, perceptual reasoning, working memory, and processing speed. We used multiple informant models to estimate covariate-adjusted differences in WISC-IV scores by repeated ln-transformed PFAS. Prenatal and childhood perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were not associated with WISC-IV measures. We observed an increase of 4.1-points (95% CI 0.3, 8.0) and 5.7-points (95% CI 1.2, 10.2) in working memory with 1-ln unit increase in prenatal perfluorooctanoate (PFOA) and perfluorononanoate (PFNA), respectively. In addition, PFNA at 3 years was associated with better FSIQ and perceptual reasoning. Child sex modified the relationship between prenatal PFOA and FSIQ; the association was positive in females only. Sex also modified the association between concurrent PFOS and FSIQ, with males having higher scores. We did not observe adverse associations between prenatal and childhood PFAS and cognitive function at age 8 years.


Expanded carrier screening in Chinese patients seeking the help of assisted reproductive technology.
Expanded carrier screening (ECS) has emerged as an effective approach to identify at-risk couples (ARCs)-before they initiate attempts at reproduction-who possess a high probability of having a child affected by severe recessive diseases. The objective of this study was to evaluate the clinical utility of ECS in Chinese patients seeking the help of assisted reproductive technology (ART). An ECS test, which covers 201 genes implicated in 135 recessive (autosomal or X-linked) diseases, was routinely offered to all ART patients in a single genetics and in vitro fertilization clinic. Additional options for preimplantation or prenatal genetic diagnosis were discussed and offered to all ARCs. All ECS results were aggregated and the clinical decisions of the ARCs were surveyed. A total of 2,923 ART patients, representing 1,462 couples, were screened. Overall, 46.73% of the individuals were found to be the carriers for at least 1 of the 135 diseases. Of the tested couples, 2.26% (n = 33) were identified as ARCs. As of the completion of this study, 21 (63.6%) ARCs have decided to avert an affected pregnancy with the help of preimplantation genetic testing for monogenetic conditions. The cumulative carrier rate of the 187 autosomal recessive genes in the ECS panel for the 2,836 Han Chinese individuals without a family history was estimated to be 45.91%. The estimated at-risk couple rate indicates that the screening for only the top 31 genes with gene carrier rates >0.5% would identify more than 94% of the ARCs identified by screening all 187 genes. Our study demonstrates that ESC yields a significant clinical value for ART patients in China. In addition, by estimating the yields of the ECS panel, we identify genes that are appropriate for screening the Han population.


The impact of vacuum-assisted closure on long-term survival after post-sternotomy mediastinitis.
Post-sternotomy mediastinitis after coronary artery bypass grafting is reported to be a strong predictor for poor late survival when using conventional wound-healing therapies. The aim of this study was to compare the long-term survival after vacuum-assisted closure treated mediastinitis following coronary artery bypass grafting with that of patients without mediastinitis. Another objective was to identify risk factors for developing mediastinitis. Forty-six patients were treated for mediastinitis, with vacuum-assisted closure but without additional tissue flaps, after isolated coronary bypass grafting between January 1999 and September 2004. During this period, 4,781 patients underwent isolated coronary bypass grafting without mediastinitis. Actuarial survival was compared with the log-rank test. Univariate and multivariate analysis were used to identify risk factors for mediastinitis. There was no difference in early or late survival between the mediastinitis group treated with vacuum-assisted closure and the control group (p = not significant). The survival at 1, 3, and 5 years was 92.9% +/- 4.0%, 89.2% +/- 5.2%, and 89.2% +/- 5.2%, respectively, in the vacuum-assisted closure group; and 96.5% +/- 0.3%, 92.1% +/- 0.5%, and 86.9% +/- 0.8%, respectively, in the control group. Diabetes mellitus, low left ventricular ejection fraction, obesity, renal failure, and three-vessel disease were identified as risk factors for developing mediastinitis. This study suggests that patients with vacuum-assisted closure treated mediastinitis may have similar long-term survival as patients without mediastinitis after coronary artery bypass grafting. The independent risk factors identified were similar to those found in previous studies. Our data support that vacuum-assisted closure therapy minimizes the negative effects of mediastinitis on late survival after coronary artery bypass grafting.


Uptake and translocation of plutonium in two plant species using hydroponics.
This study presents determinations of the uptake and translocation of Pu in Indian mustard (Brassica juncea) and sunflower (Helianthus annuus) from Pu contaminated solution media. The initial activity levels of Pu were 18.50 and 37.00 Bq ml(-1), for Pu-nitrate [239Pu(NO3)4] and for Pu-citrate [239Pu(C6H5O7)+] in nutrient solution. Plutonium-diethylenetriaminepentaacetic acid (DTPA: [239Pu-C14H23O10N3] solution was prepared by adding 0, 5, 10, and 50 microg of DTPA ml(-1) with 239Pu(NO3)4 in nutrient solution. Concentration ratios (CR, Pu concentration in dry plant material/Pu concentration in nutrient solution) and transport indices (Tl, Pu content in the shoot/Pu content in the whole plant) were calculated to evaluate Pu uptake and translocation. All experiments were conducted in hydroponic solution in an environmental growth chamber. Plutonium concentration in the plant tissue was increased with increased Pu contamination. Plant tissue Pu concentration for Pu-nitrate and Pu-citrate application was not correlated and may be dependent on plant species. For plants receiving Pu-DTPA, the Pu concentration was increased in the shoots but decreased in the roots resulting in a negative correlation between the Pu concentrations in the plant shoots and roots. The Pu concentration in shoots of Indian mustard was increased for application rates up to 10 microg DTPA ml(-1) and up to 5 microg DTPA ml(-1) for sunflower. Similar trends were observed for the CR of plants compared to the Pu concentration in the shoots and roots, whereas the Tl was increased with increasing DTPA concentration. Plutonium in shoots of Indian mustard was up to 10 times higher than that in shoots of sunflower. The Pu concentration in the apparent free space (AFS) of plant root tissue of sunflower was more affected by concentration of DTPA than that of Indian mustard.


(23R,231 S,25S)-231,26-Ep-oxy-23-ethyl-furost-20(22)-en-3β-ol.
The title compound, C29H46O3, is a steroid synthesized through a rearrangement of a sarsasapogenin derivative in acidic medium. The newly formed ring F is a tetra-hydro-2H-pyran heterocycle substituted by two methyl groups placed in equatorial positions. This ring displays a chair conformation, while di-hydro-furan ring E, to which it is bonded, has an envelope conformation. The mol-ecules are associated by weak O-H⋯O hydrogen bonds to form chains running in the [101] direction in the crystal.


Role of Orthopantomogram in Unexplained Earache.
Earache is one of the most common symptom for a patient to visit ENT doctor. It poses difficulty to diagnose the root cause when ENT examination is normal and still the pain persists, hence many a times patients are presumed to have psychosomatic element. While evaluation of earache dental status is often overlooked. 93 such patients of persistent earache with normal ENT examination were evaluated. In 70 of these patients the earache was attributed to either absent, unerupted or obliquely positioned upper or lower last molars which was confirmed by Orthopantomogram.


Muscle-Specific Relation of Acetylcarnitine and Intramyocellular Lipids to Chronic Hyperglycemia: A Pilot 3-T 1H MRS Study.
Acetylcarnitine plays an important role in fat metabolism and can be detected in proton magnetic resonance spectra in skeletal muscle. An inverse relationship of acetylcarnitine to intramyocellular lipids and metabolic markers of chronic hyperglycemia has been suggested. This study aimed to compare the acetylcarnitine concentrations and intramyocellular lipids measured noninvasively by proton magnetic resonance spectroscopy (1H MRS) in the tibialis anterior and the soleus of three different groups of volunteers with a broad range of glycemic control. Acetylcarnitine and intramyocellular lipid concentrations were measured in 35 individuals stratified into three groups according to glucose tolerance and/or manifestation of type 2 diabetes mellitus. All MRS measurements were performed on a 3-T MR system. The differences in patient phenotype were mirrored by increased intramyocellular lipids in the tibialis anterior and decreased acetylcarnitine concentrations in the soleus muscle of type 2 diabetes patients when compared with normal glucose-tolerant individuals. Results suggest that intramyocellular lipids mirror whole-body glucose tolerance better in the tibialis anterior muscle, whereas acetylcarnitine is a better discriminator in the soleus muscle. This muscle-specific behavior of metabolites could represent different fiber compositions in the examined muscles and should be considered when planning future metabolic studies.


Systematic prevention of bubble formation and accumulation for long-term culture of pancreatic islet cells in microfluidic device.
Reliable long-term cell culture in microfluidic system is limited by air bubble formation and accumulation. In this study, we developed a bubble removal system capable of both trapping and discharging air bubbles in a consistent and reliable manner. Combined with PDMS (Polydimethylsiloxane) hydrophilic surface treatment and vacuum filling, a microfluidic perifusion system equipped with the bubble trap was successfully applied for long-term culture of mouse pancreatic islets with no bubble formation and no flow interruption. In addition to demonstrating normal cell viability and islet morphology, post-cultured islets exhibited normal insulin secretion kinetics, intracellular calcium signaling, and changes in mitochondrial potentials in response to glucose challenge. This design could be easily adapted by other microfluidic systems due to its simple design, ease of fabrication, and portability.


Constructing pH-Responsive and Tunable Azo-Phenol-Based o-Nitrobenzyl Photocages.
Multiple triggered-release strategies are widely utilized to control the release of caged target molecules. Among them, photocages with conditional triggers provide extra layers of control in photorelease. In this work, a series of pH-responsive photocages was designed that could be triggered under irradiation and specific intracellular pH values. pH-sensitive phenolic groups were conjugated with o-nitrobenzyl (oNB) to form azo-phenolic NPX photocages with tunable pKa. These azo-phenol-based oNB photocages showed differentiable photoreleasing profiles at pH 5.0, 7.2 and 9.0. By attaching fluorogenic cargos, it was shown that one of the photocages, NPdiCl, could be used to differentiate between acidic pH 5.0 and neutral pH 7.2 in cells under artificial pH conditions. Finally, NPdiCl was identified as a promising pH-responsive photocage for photoreleasing cargo inside acidic tumor cells.


Predicting the functional consequences of genetic variants in co-stimulatory ligand B7-1 using in-silico approaches.
The purpose of this research is to identify and characterize deleterious genetic variants in the co-stimulatory ligand B7-1, also known as the human cluster of differentiation CD80 marker. The B7-1 ligand and the major histocompatibility complex class II (MHC II) molecules are the main determinants that provide B-cells the required competency to act as antigen presenting cells. For this, participation of both MHC class II molecules and CD80 is required. The interaction of the CD80 ligand with CD28 on the surface 7 of TH cells plays a key role in the activation of TH cells and progression of B cells through the S phase, hence, leading to their proliferation in mitosis. A set of 2313 genetic variants in the B7-1 ligand have been mapped and retrieved from dbSNP database. Subsequently, 150 non-synonymous single nucleotide polymorphisms (nsSNPs) were mapped and subjected to the sequence and structural homology based predictions, which were further analyzed for protein stability and the disease phenotypes. Finally, we identified 7 potentially damaging nsSNPs in the B7-1 ligand that may affect its interaction with the cognitive receptor CD28, hence, may also interfere with TH cell activation and B cell proliferation. We propose that subsequent experimental analyses (stability, expression and interactions) on these proteins can provide a deep understanding about the effect of these variants on the structure and function of CD80.


A negative modulatory role for rho and rho-associated kinase signaling in delamination of neural crest cells.
Neural crest progenitors arise as epithelial cells and then undergo a process of epithelial to mesenchymal transition that precedes the generation of cellular motility and subsequent migration. We aim at understanding the underlying molecular network. Along this line, possible roles of Rho GTPases that act as molecular switches to control a variety of signal transduction pathways remain virtually unexplored, as are putative interactions between Rho proteins and additional known components of this cascade. We investigated the role of Rho/Rock signaling in neural crest delamination. Active RhoA and RhoB are expressed in the membrane of epithelial progenitors and are downregulated upon delamination. In vivo loss-of-function of RhoA or RhoB or of overall Rho signaling by C3 transferase enhanced and/or triggered premature crest delamination yet had no effect on cell specification. Consistently, treatment of explanted neural primordia with membrane-permeable C3 or with the Rock inhibitor Y27632 both accelerated and enhanced crest emigration without affecting cell proliferation. These treatments altered neural crest morphology by reducing stress fibers, focal adhesions and downregulating membrane-bound N-cadherin. Reciprocally, activation of endogenous Rho by lysophosphatidic acid inhibited emigration while enhancing the above. Since delamination is triggered by BMP and requires G1/S transition, we examined their relationship with Rho. Blocking Rho/Rock function rescued crest emigration upon treatment with noggin or with the G1/S inhibitor mimosine. In the latter condition, cells emigrated while arrested at G1. Conversely, BMP4 was unable to rescue cell emigration when endogenous Rho activity was enhanced by lysophosphatidic acid. Rho-GTPases, through Rock, act downstream of BMP and of G1/S transition to negatively regulate crest delamination by modifying cytoskeleton assembly and intercellular adhesion.


Four-week repeated exposure to tire-derived 6-PPD quinone causes multiple organ injury in male BALB/c mice.
N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6-PPDQ) is the ozonation product of tire antioxidant 6-PPD. 6-PPDQ can be detected in different environments, such as roadway runoff and dust. Although 6-PPDQ toxicity has been frequently assessed in aquatic organisms, the possible toxic effects of 6-PPDQ on mammals remain largely unclear. We here aimed to perform systematic assessment to evaluate 6-PPDQ toxicity on multiple organs in mice. Male BALB/c mice were intraperitoneally injected with 6-PPDQ for two exposure modes, single intraperitoneal injection and repeated intraperitoneal injection every four days for 28 days. Serum, liver, kidney, lung, spleen, testis, brain, and heart were collected for injury evaluation by organ index, histopathology analysis and biochemical parameters. In 0.4 and 4 mg/kg 6-PPDQ single injected mice, no significant changes in organ indexes and biochemical parameters were detected, and only moderate pathological changes were observed in organs of liver, kidney, lung, and brain. Very different from this, in 0.4 and 4 mg/kg 6-PPDQ repeated injected mice, we observed the obvious increase in organ indexes of liver, kidney, lung, testis, and brain, and the decrease in spleen index. Meanwhile, the significant pathological changes were formed in liver, kidney, lung, spleen, testis, and brain in 0.4 and 4 mg/kg 6-PPDQ repeated injected mice. Biochemical parameters of liver (alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP)) and kidney (urea and creatinine) were all significantly upregulated by repeated injection with 0.4 and 4 mg/kg 6-PPDQ. After repeated exposure, most of 6-PPDQ was accumulated in liver and lung of mice. Therefore, our results suggested the risk of repeated exposure to 6-PPDQ in inducing toxicity on multiple organs in mice.


A Case Study of Zoonotic Chlamydia abortus Infection: Diagnostic Challenges From Clinical and Microbiological Perspectives.
Chlamydia abortus is the most common causative agent of abortion in small ruminants, but it is poorly recognized as a human pathogen. In most published case studies, diagnosis remained difficult and often resulted in delayed initiation of therapy. In this case study of severe C abortus infection in a pregnant farmer from Switzerland, we highlight the clinical and microbiological diagnostic challenges and provide evidence of a zoonotic epidemiological link.


Paradoxical activation of transcription factor SREBP1c and de novo lipogenesis by hepatocyte-selective ATP-citrate lyase depletion in obese mice.
Hepatic steatosis associated with high-fat diet, obesity, and type 2 diabetes is thought to be the major driver of severe liver inflammation, fibrosis, and cirrhosis. Cytosolic acetyl CoA (AcCoA), a central metabolite and substrate for de novo lipogenesis (DNL), is produced from citrate by ATP-citrate lyase (ACLY) and from acetate through AcCoA synthase short chain family member 2 (ACSS2). However, the relative contributions of these two enzymes to hepatic AcCoA pools and DNL rates in response to high-fat feeding are unknown. We report here that hepatocyte-selective depletion of either ACSS2 or ACLY caused similar 50% decreases in liver AcCoA levels in obese mice, showing that both pathways contribute to the generation of this DNL substrate. Unexpectedly however, the hepatocyte ACLY depletion in obese mice paradoxically increased total DNL flux measured by D2O incorporation into palmitate, whereas in contrast, ACSS2 depletion had no effect. The increase in liver DNL upon ACLY depletion was associated with increased expression of nuclear sterol regulatory element-binding protein 1c and of its target DNL enzymes. This upregulated DNL enzyme expression explains the increased rate of palmitate synthesis in ACLY-depleted livers. Furthermore, this increased flux through DNL may also contribute to the observed depletion of AcCoA levels because of its increased conversion to malonyl CoA and palmitate. Together, these data indicate that in fat diet-fed obese mice, hepatic DNL is not limited by its immediate substrates AcCoA or malonyl CoA but rather by activities of DNL enzymes.


Trapping of reactive carbonyl species by fiber-bound polyphenols from whole grains under simulated physiological conditions.
The carbonyl trapping activity of bound-polyphenol rich insoluble dietary fiber (BP-IDF) from different whole grains and underlying mechanism of these BP-IDF actions were studied under simulated physiological conditions. We found that the black highland barley BP-IDF exhibited the most pronounced effect in scavenging carbonyls by trapping 88.7%, 72.2%, 95.7%, and 31.4% for methylglyoxal, glyoxal, acrolein, and malondialdehyde within 24 h, respectively. After vitro gastrointestinal digestion, the black highland barley BP-IDF still retained considerable trapping activity for carbonyls. The carbonyl scavenging capacity was reduced by up to 93% after removing bound polyphenols from the black highland barley BP-IDF, which was consistent with the reduction in its total phenolic content. Moreover, the formation of adducts between reactive carbonyl species (RCS) and polyphenols bound to insoluble dietary fiber (IDF) was also detected. Overall, these findings confirmed that IDF-bound polyphenols were still active to trap RCS, indicating the potential benefits of BP-IDF from whole grains as functional ingredients to limit carbonyl stress across the gastrointestinal tract.


Human immunodeficiency virus in breast milk.
As the acquired immunodeficiency syndrome (AIDS) epidemic spreads to the pediatric population, a recommendation is made for more research on mother-to-infant human immunodeficiency virus (HIV) transmission, in light of current policies, and the scientific community is challenged to re-evaluate its attitude to the pathogenesis of HIV transmission by breast milk.


The incidence and risk factors of osteoarthritis following osteochondritis dissecans of the knees: a systematic review and meta-analysis.
The current systematic review and meta-analysis aim to pool together the incidence and risk factors of osteoarthritis following osteochondritis dissecans of the knee. The systematic review was conducted according to PRISMA guidelines. A search was conducted using PubMed and Cochrane Library with the keywords being "knee" and "osteochondritis dissecans" or "osteochondral lesion". All original human studies that reported the incidence or risk factors of osteoarthritis following osteochondritis dissecans of the knee were included. Nine studies with 496 patients were included. The incidence of osteoarthritis following osteochondritis dissecans is 0.39 (95% CI 0.19-0.59). Patients with a body mass index greater than 25 kg/m2 had a significantly increased risk of osteoarthritis. Fragment excision had an increased relative risk of 1.89 (95% CI 1.19-3.01) of osteoarthritis as compared to fragment preservation. Significant heterogeneity was identified when comparing between juvenile and adult osteochondritis dissecans. The size of the lesions moderated the between-study heterogeneity with regards to the incidence of osteoarthritis, with the relative risk of osteoarthritis in lesions bigger than 4 cm2 being 2.29 (95% CI 1.24-4.23). No other risk factors, including gender of the patient, location of osteochondritis dissecans, stability of osteochondritis dissecans, and surgical versus non-surgical management were significant risk factors. Significant risk factors for osteoarthritis were increased body mass index and fragment excision. Probable but inconclusive risk factors were the age of the patients and the size of the osteochondritis dissecans. The gender of the patient, location of osteochondritis dissecans, the stability of osteochondritis dissecans, and surgical versus non-surgical management of osteochondritis dissecans when appropriate were not significant risk factors.


DNA methylation in the promoter region of the p16 (CDKN2/MTS-1/INK4A) gene in human breast tumours.
The p16 (CDKN2/MTS-1/INK4A) gene is one of several tumour-suppressor genes that have been shown to be inactivated by DNA methylation in various human cancers including breast tumours. We have used bisulphite genomic sequencing to examine the detailed sequence specificity of DNA methylation in the CpG island promoter/exon 1 region in the p16 gene in DNA from a series of human breast cancer specimens and normal human breast tissue (from reductive mammaplasty). The p16 region examined was unmethylated in the four normal human breast specimens and in four out of nine breast tumours. In the other five independent breast tumour specimens, a uniform pattern of DNA methylation was observed. Of the nine major sites of DNA methylation in the amplified region from these tumour DNAs, four were in non-CG sequences. This unusual concentration of non-CG methylation sites was not a general phenomenon present throughout the genome of these tumour cells because the methylated CpG island regions of interspersed L1 repeats had a pattern of (almost exclusively) CG methylation similar to that found in normal breast tissue DNA and in DNA from tumours with unmethylated p16 genes. These data suggest that DNA methylation of the p16 gene in some breast tumours could be the result of an active process that generates a discrete methylation pattern and, hence, could ultimately be amenable to therapeutic manipulation.


Application of cold atmospheric microwave plasma as an adjunct therapy for wound healing in dogs and cats.
Cold atmospheric plasma is a novel innovative approach for wound care, and it is currently underrepresented in veterinary medicine. To investigate the efficacy and safety of using cold atmospheric microwave plasma (CAMP) as an adjunct therapy for wound healing in dogs and cats. Wound healing outcomes were retrospectively analyzed using clinical records of client-owned dogs and cats who were first managed through standard wound care alone (pre-CAMP period) and subsequently via CAMP therapy (CAMP period). The degree of wound healing was estimated based on wound size and a modified wound scoring system. Of the 27 acute and chronic wounds included in the analysis, 81.48% showed complete healing after the administration of CAMP as an adjunct therapy to standard care. Most wounds achieved complete healing in < 5 weeks. Compared with the pre-CAMP period, the rate of wound healing significantly increased every week in the CAMP period in terms of in wound size (first week, p < 0.001; second week, p = 0.012; third week, p < 0.001) and wound score (first week, p < 0.001; second week, p < 0.001; third week, p = 0.001). No adverse events were noted except for mild discomfort and transient erythema. CAMP is a well-tolerated therapeutic option with immense potential to support the treatment of wounds of diverse etiology in small animal practice. Further research is warranted to establish specific criteria for CAMP treatment according to wound characteristics.


Ionic channels in excitable membranes. Current problems and biophysical approaches.
Ionic channels are gated aqueous pores whose conformational changes are driven by the electric field in the membrane. Gating may be studied by three electrical methods: ionic current transients, ionic current fluctuations, and "gating current," and probably occurs through a series of conformational changes in the channel leading to an all-or-nothing opening of the pore. When the potential is held constant, the gating steps come to equilibrium rather than reaching an energy-dissipating, cyclic steady state. The kinetic models now in use eventually need to be changed to correct disagreements with several recent studies. Diffusion of ions through open channels is very fast but involves many interactions of ions, pore, and solvent that lead to ionic selectivity, saturation, block, and flux coupling. Our description of the ionic fluxes can be improved by abandoning continuum models in favor of more structured ones. Problems to be solved include determining how many ions occupy a channel at once and what to be solved include determining how many ions occupy a channel at once and what kind of energy barriers they must cross in traversing the membrane. Ultimately we will need to know the chemical structure of the whole system to understand how it functions.


Cochlear implant performance in geriatric patients.
To evaluate the hearing performance with cochlear implants (CIs) in patients who were 70 years or older at the time of implantation (geriatric patients) and compare it with the performance in younger adults. Individual, retrospective, cohort study. A cohort of 1,005 postlingually deafened adults was selected for this study. According to their age at the time of cochlear implantation, patients were divided into four age groups: group 1, 18 to 39 years; group 2, 40 to 59 years; group 3, 60 to 69 years; and group 4, 70 years and older). The test battery was composed of four standard German speech tests: Freiburger Monosyllabic Test, Speech Tracking Test, and Hochmair-Schulz-Moser (HSM) Sentence Test in quiet and in 10 dB noise. Geriatric patients showed a similar learning curve as the younger adults in the first 2 years after implantation. The direct comparison of speech perception in the Freiburger Monosyllabic Test, Speech Tracking Test, and HSM Test in quiet revealed no differences between the average performance of the geriatric patients and younger adults. However, in the HSM Test in noise, the performance of the geriatric group was significantly lower than the younger adults. Geriatric CI patients have a similar learning curve to younger adults, and in speech tests in quiet they show a comparable performance. However, their performance is significantly lower in noisy surroundings. This may be due to the central presbycusis in patients older than 70 years and should be taken into account in postoperative fitting of these patients. Further prospective studies are required to evaluate the role of special rehabilitation methods and cognitive training to improve the speech perception in noise in geriatric CI patients.


The antioxidative properties of carnosine, a natural histidine containing dipeptide.
The experimental results suggest that the antioxidative function of carnosine is one of the most important manifestations of its biological role. The ability of carnosine to interact directly with lipid peroxidation products was demonstrated. The effects of carnosine on partial restoration of lens transparency in dog eyes with senile cataract which is known to be caused by lipid peroxidation were demonstrated "in vitro" and "in vivo".


Changing prevalence of human microsporidiosis.
The frequency of publications about microsporidiosis, indexed in PubMed, was tracked on a yearly basis from 1980 to 2010. Search terms (individual and paired) of various degrees of restrictiveness were used (ranging from least restrictive: 'microsporidia', to most restrictive: 'microsporidiosis/HIV', 'microsporidiosis/AIDS'). The annual number of publications indexed under each search term(s) increased from the early 1980s until the mid 1990s. In subsequent years, there was a decline in numbers of publications retrievable via search terms emphasising human disease. This decline mirrors the declining prevalence of microsporidian infections in the HIV-infected population since the mid to late 1990s.


Thermochemical stabilities of giant fullerenes using density functional tight binding theory and isodesmic-type reactions.
We present a systematic assessment of the density functional tight binding (DFTB) method for calculating heats of formation of fullerenes with isodesmic-type reaction schemes. We show that DFTB3-D/3ob can accurately predict Δf H values of the 1812 structural isomers of C60 , reproduce subtle trends in Δf H values for 24 isolated pentagon rule (IPR) isomers of C84 , and predict Δf H values of giant fullerenes that are in effectively exact agreement with benchmark DSD-PBEP86/def2-QZVPP calculations. For fullerenes up to C320 , DFTB Δf H values are within 1.0 kJ mol-1 of DSD-PBEP86/def2-QZVPP values per carbon atom, and on a per carbon atom basis DFTB3-D/3ob yields exactly the same numerical trend of (Δf H [per carbon] = 722n-0.72 + 5.2 kJ mol-1 ). DFTB3-D/3ob is therefore an accurate replacement for high-level DHDFT and composite thermochemical methods in predicting of thermochemical stabilities of giant fullerenes and analogous nanocarbon architectures.


Globally consistent depth sorting of overlapping 2D surfaces in a model using local recurrent interactions.
The human visual system utilizes depth information as a major cue to group together visual items constituting an object and to segregate them from items belonging to other objects in the visual scene. Depth information can be inferred from a variety of different visual cues, such as disparity, occlusions and perspective. Many of these cues provide only local and relative information about the depth of objects. For example, at occlusions, T-junctions indicate the local relative depth precedence of surface patches. However, in order to obtain a globally consistent interpretation of the depth relations between the surfaces and objects in a visual scene, a mechanism is necessary that globally propagates such local and relative information. We present a computational framework in which depth information derived from T-junctions is propagated along surface contours using local recurrent interactions between neighboring neurons. We demonstrate that within this framework a globally consistent depth sorting of overlapping surfaces can be obtained on the basis of local interactions. Unlike previous approaches in which locally restricted cell interactions could merely distinguish between two depths (figure and ground), our model can also represent several intermediate depth positions. Our approach is an extension of a previous model of recurrent V1-V2 interaction for contour processing and illusory contour formation. Based on the contour representation created by this model, a recursive scheme of local interactions subsequently achieves a globally consistent depth sorting of several overlapping surfaces. Within this framework, the induction of illusory contours by the model of recurrent V1-V2 interaction gives rise to the figure-ground segmentation of illusory figures such as a Kanizsa square.


Adjusted degradation of BRD4 S and BRD4 L based on fine structural modifications of the pyrrolopyridone scaffold.
Novel pyrrolopyridone BET degraders were designed and synthesized based on the binding mode between the pyrrolopyridone BET inhibitor with the BRD4 protein. The potent degraders on MV-4-11 cells were discovered through structure-activity relationship study. Modification of warhead on pyrrolopyridone BET degraders significantly regulates BRD4 isoform (long and short) protein degradation, which induces differential cell cycle arrest and apoptosis on MV-4-11 cells. Docking study revealed that the fine structural modification of BET degraders may bind with the BD domain of BRD4 protein to engage various surface areas that bind with CRBN.


Diagnosis and misdiagnosis of necrotizing soft tissue infections: three case reports.
Today, gas gangrene is rare, but still many of the patients die, despite having received timely treatment. This report highlights the cases of three different patients, who were transferred to our surgical department in 2006. The first patient (Patient_A), with the suspected diagnosis "femoral hematoma", a second patient (Patient_B) because of an "acute abdomen" and the third patient (Patient_C) with suspected gas gangrene of the right leg. The first two cases demonstrate gas gangrene should always be kept in mind, especially in high-risk-patients. Though, the third case shows that severe consequences because of a precipitate diagnosis can be avoided by careful evaluation.


Frequency of Drug Induced Acute Kidney Injury in Pediatric Intensive Care Unit.
Acute kidney injury (AKI) is known to complicate one-third of cases in pediatric intensive care units (PICU), and almost one-fourth of these are due to nephrotoxic drugs (NTDs). Although stopping NTDs seems the most obvious option, it is not practically applicable. Many NTDs are the only existing option, and their potential benefits outweigh the risk of drug-induced AKI. To assess the proportion of children receiving NTDs in the PICU and highlight the children who developed AKI. A prospective observational study was conducted in the PICU of the National Institute of Child Health, Karachi. All children admitted to the PICU for at least 72 hours not diagnosed with any acute or chronic kidney disease were included. Serum creatinine (SCr) was done at admission and then after 72 hours. Data was entered and analyzed using IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp. Of 99 children, 53 (53.5%) were male. NTD exposure was positive in 97 (97.9%), and 72 (72.7%) had high exposure (≥3 NTDs). Drug-induced AKI was diagnosed in 46 (46.5%). It was significantly related to high SCr even at admission and high NTDs exposure. The mortality rate in the AKI group was 17% compared to 4% in the non-AKI (p=0.02). Almost half of all PICU admissions were infants. Almost all patients were exposed to NTDs, and three-fourth experienced high exposure. AKI developed in 46% of patients and may be predicted by raised creatinine at the time of admission. Children exposed to ≥3 NTDs had a higher chance of drug-induced AKI.