Considerations in spontaneous quadriceps tendon rupture repair in end-stage renal disease patients: A case report.
Spontaneous quadriceps tendon rupture (SQTR) is a rare injury to the knee extensor mechanism that is usually associated with systemic diseases such as end stage renal diseases (ESRD) and it is more prevalent in the elderly. Due to the underlying pathology, quadriceps tendon rupture warrants special considerations and management in its repair. We present two cases of quadriceps tendon rupture in end-stage renal disease (ESRD) patients. The first case; a 57 years old female who had bilateral SQTR and is undergoing hemodialysis. The second patient, a 26 years old male had unilateral quadriceps tendon rupture caused by minimal trauma. The first patient had a trans-osseous repair by direct suturing the quadriceps tendon stump to the proximal pole patella. The second patient was repaired with a modified Bunnel suture and anchor placement on the proximal pole patella. The first case had a re-rupture of the right quadriceps tendon and the second case has recovered with improved outcomes. Spontaneous quadriceps tendon rupture is usually underlined by degenerative changes of the tendons. Special care is needed to address the pathologic tendon underlying SQTR. The current surgical literature still lacks the statistical data that shows which surgical approach is most optimal for SQTR in ESRD patients. SQTR rupture is generally an injury of brittle tendons caused by underlying diseases. A multidisciplinary and comprehensive approach including a proper surgical approach and postoperative managements are crucial for good functional outcomes of the extensor mechanism.


The effect of mechanical loading on the MyHC synthesis rate and composition in rat plantaris muscle.
The aim of this study was to investigate the response of protein synthesis rate, particularly myosin heavy chain (MyHC) isoforms synthesis and the magnitude of its isoform transformation in fast-twitch plantaris muscle, to different modes of prolonged mechanical loading. Different protocols of mechanical loading were used: resistance training (RT), compensatory hypertrophy (CH) of m. plantaris after tenotomy of m. gastrocnemius and a combination of the two previous loadings (RT + CH). During the different modes of loading, plantaris muscle hypertrophy in RT group was approximately 10 %, CH approximately 40 % and CH + RT approximately 44 %. MyHC I and IID isoform synthesis rate increased in all experimental groups, as well as their relative content. MyHC IIA relative content decreased during RT and RT + CH and increased during CH. MHC IIB isoform relative content decreased in all experimental groups, but compared with CH in CH + RT MyHC IIB isoform content increased in plantaris muscle. These results demonstrate that different modes of mechanical loading resulted in the selective up- and down-regulation of MyHC isoforms in fast-twitch skeletal muscle. The synthesis rate and relative content of the two fastest isoforms of MyHC IIB and IID are regulated to different directions during mechanical loading.


3D QSAR analysis of 2-(substituted aryl)-thiazolidine-4-carboxamides as potent antitubercular agents.
Thiazolidine-4-carboxylic acid derivatives were recognized recently for their potent antitubercular activity. A total of sixty four thiazolidine derivatives published in the recent times were collected and 3D QSAR models were developed, using CoMFA and COMSIA with high predictability. Later, we selected three new molecules, recently synthesized in our lab and evaluated them using the developed QSAR models. The in vitro antitubercular activity (MIC) obtained for these new molecules is in agreement with the predicted values (pMIC).


Thyroid eye disease (TED)--a current understanding.
Thyroid Eye Disease (TED) provides a clinical meeting place for physician, ophthalmologist and immunologist. Some past difficulties in understanding this disease may have reflected too narrow specialization. In this presentation only three eponymous terms will be used --Graves' Disease, Plummer's Disease and Hashimoto's Disease.


Dental amalgam stabilization by selective interfacial amalgamation.
The purpose of this investigation was to explore the feasibility of enhancing the electrochemical stability of dental amalgam restorations by a process of "selective interfacial amalgamation." If dental amalgam restorations can be selectively alloyed at the tooth-amalgam interface, to a minor thickness as compared with the dimensions of the bulk amalgam, so as to present a more electrochemically stable phase than psi2 to the oral environment, corrosion will be reduced and desirable qualities of existing amalgams can be utilized. It was found that selective interfacial amalgamation was indeed possible and that it could be readily accomplished using a silver suspension as a cavity liner. By then placing a conventional silver-tin amalgam according to ordinary dental techniques, mercury expressed during hand condensing reacted with the silver in the liner resulting in the formation of an integral amalgam restoration with the more noble psi1 phase adjacent to tooth structure. In vitro corrosion tests of samples so prepared exhibited corrosion resistance far superior to unlined control samples.


[Spontaneous variability of ventricular arrhythmias in follow-up of anti-arrhythmia therapy].
The question of the reliability of ambulatory Holter monitoring for assessment of antiarrhythmic treatment has not been adequately resolved. Even though treatment efficacy had been individually assessed with Holter monitoring in the CAST study, during long-term treatment with class IC antiarrhythmic drugs, there were more deaths among patients receiving active drug than in those in the placebo group. Basic biostatistical considerations: Due to the spontaneous variability of frequency and complexity of ventricular arrhythmias, parametric models were developed with the aid of which normal ranges for spontaneous variability of singular ventricular premature complexes (VPC), couplets and salvos can be calculated. We designed a model which enables rapid visual analysis of the results: spontaneous variability = log (EE Day 2 + 0.01/EE Day 1 + 0.01) where EE is the number of ectopic events. For both days, the mean values per hour are applied. The use of parametric models prerequisites normal distribution of the data which can be achieved with logarithmic transformation. A constant is added to all mean values to preclude the mathematically-inadmissible form of log 0. The magnitude of the constant results in some degree of underestimation of the spontaneous variability. We chose the smallest constant, c = 0.01, consistent with a normal distribution of data. Figure 1 shows the normal range of the variability quotients for VPC in patients with cardiac disease and complex ventricular arrhythmias. The contiguous regions above and below the normal range designate active areas indicative of reduction or aggravation. Determinants of spontaneous variability: Frequency of arrhythmias: The number of VPC per unit of time exerts considerable influence on the spontaneous variability. The more infrequent an arrhythmia, the greater is the fluctuation to be anticipated. The differences in the variability of VPC, couplets and salvos are almost exclusively due to their differing frequencies since, in the presence of comparable frequency, they cannot be distinguished statistically from each other (Figure 2). Type and extent of underlying cardiac disease: In our patient population, there were no differences in spontaneous variability of arrhythmias between patients with coronary artery disease and those with dilated cardiomyopathy (Figure 3). Although in patients with coronary artery disease, as compared to those with noncoronary disease, a higher degree of spontaneous variability has been reported for VPC but, due to the inhomogeneity of the latter group, valid comparison is encumbered. The ejection fraction, the left ventricular filling pressure and the end-diastolic volume do not exert meaningful influence on the spontaneous variability (Figures 4 to 6).(ABSTRACT TRUNCATED AT 400 WORDS)


Recent advances in permeable polymersomes: fabrication, responsiveness, and applications.
Polymersomes are vesicular nanostructures enclosed by a bilayer-membrane self-assembled from amphiphilic block copolymers, which exhibit higher stability compared with their biological analogues (e.g. liposomes). Due to their versatility, polymersomes have found various applications in different research fields such as drug delivery, nanomedicine, biological nanoreactors, and artificial cells. However, polymersomes prepared with high molecular weight components typically display low permeability to molecules and ions. It hence remains a major challenge to balance the opposing features of robustness and permeability of polymersomes. In this review, we focus on the design and strategies for fabricating permeable polymersomes, including polymersomes with intrinsic permeability, the formation of nanopores in the membrane bilayers by protein insertion, and the construction of stimuli-responsive polymersomes. Then, we highlight the applications of permeable polymersomes in the fields of biomimetic nanoreactors, artificial cells and organelles, and nanomedicine, to underline the challenges in the development of polymersomes as soft matter with biomedical utilities.


The effects of surface adsorption on the thermal stability of proteins.
The effect of surface adsorption on the structure and stability of proteins is a matter of increasing interest in biotechnology. Therefore, we have examined the effect of adsorption to silica on the thermal stability of 7 proteins employing differential scanning calorimetry (DSC) and front surface fluorescence (FSF) spectroscopy. In general, it was found that surface adsorption decreased the thermal stability of the bound protein. Using lysozyme for further studies, DSC, FSF, and FTIR spectroscopies, as well as enzymatic activity measurements, were used to explore the effect of decreasing surface apolarity on stability. It was observed that increasing surface apolarity produced decreasing stability and increasing structural alteration of the adsorbed protein.


Experimental investigation of the onset of instability in a radial Hele-Shaw cell.
The initial stage of interface instability upon radial displacement of a fluid in a Hele-Shaw cell is investigated. An air-silicone oil system is analyzed. The critical radii of stability relative to long-wave perturbations are determined. It is found that, in the investigated range of parameters, instability most often begins by a translational mechanism. It is ascertained that in the overwhelming majority of cases the critical radii of instability are smaller than the values predicted by the linear stability theory and external effects make this difference even greater. The obtained results are discussed and compared with the existing theories.


Chronic Renal Failure Secondary to Unrecognized Neurogenic Bladder in A Child with Myelodysplasia.
Myelodysplasia includes a group of developmental anomalies resulting from defects that occur during neural tube closure. Urological morbidity in patients with myelodysplasia is significant and if not treated appropriately in a timely manner can potentially lead to progressive renal failure, requiring dialysis or transplantation. We report the case of a 13-year old girl with neurogenic bladder who presented chronic renal failure secondary to lipomyelomeningocele with retethering of cord. She was managed with urinary indwelling catheterization until optimization of renal function and then underwent detethering of cord with excision and repair of residual lipomeningomyelocele. Her renal parameters improved gradually over weeks and then were managed on self clean intermittent catheterization. The case emphasizes the need for considering retethering of spinal cord in children with myelodysplasia where symptoms of neurogenic bladder and recurrent urinary tract infections occur.


Synthesis and characterization of coinage metal aluminum sulfur species.
The synthesis of heterobimetallic cluster with the Al-S-M (M = Cu and Ag) structural unit has been realized for the first time by the reaction of aluminum-dithiol LAl(SH)2 (L = HC[C(Me)N(Ar)]2, Ar = 2,6-iPr2C6H3) with (MesCu)4 and (MesAg)4 (Mes = 2,4,6-Me3C6H2), respectively. The isolated clusters exhibit core structures of Al2Cu4S4 and Al4Ag8S8, respectively. During the formation of the [LAl(SAg)2]4, a side product of LAlS6 is formed. However, the reaction of LAl(SH)2 with excess of sulfur and (MesAg)4 resulted in the formation of LAlS4 as the only product soluble in organic solvents. Both of them represent rare examples of aluminum polysulfides. All compounds were characterized by spectroscopic methods and single crystal X-ray diffraction studies.


Effect of CP55,940 on mechanosensory spinal neurons following chronic inflammation.
Cannabinoid receptor agonists have previously been shown to produce antinociceptive effects in rodent models of inflammatory pain. In the present study, we characterized responses of spinal dorsal horn neurons receiving sensory input from the hind paw in rats that had received intraplantar injection of complete Freund's adjuvant (CFA), and examined effects of the nonselective CB1/2 receptor agonist CP55,940 on spinal neuron responses. Systemic (i.v.) administration of CP55,940 failed to attenuate responses of dorsal horn neurons to noxious mechanical stimulation in naïve rats, but significantly reduced responses in CFA-inflamed rats to 25.78+/-13.7% of vehicle control at a cumulative dose of 0.8 mg/kg (ID50=0.28+/-0.02 mg/kg). Additionally, local administration of CP55,940 (10 microM) to the spinal cord reduced responses of mechanosensory dorsal horn neurons in CFA-inflamed rats to 67.15+/-7.1% of vehicle control. The inhibitory action of CP55,940 on spinal dorsal horn neurons in CFA-inflamed rats was mediated by CB1 receptors since local pretreatment with the CB1 receptor antagonist AM251 (10 microM) blocked this effect, while the CB2 receptor antagonist AM630 (10 microM) was ineffective. Our results suggest that following inflammation, the inhibition of spinal nociceptive transmission by CP55,940 is mediated in part by spinal CB1 receptors, and not spinal CB2 receptors.


Gonadal shield.
A secondary gonadal shield for use in the pelvic irradiation of males was designed and built using material and apparatus available with the Cerrobend blocking system. The gonadal dose was reduced to approximately 1.5 to 2.5% of the given dose.


Tyrosine Detoxification Is an Essential Trait in the Life History of Blood-Feeding Arthropods.
Blood-feeding arthropods are vectors of infectious diseases such as dengue, Zika, Chagas disease, and malaria [1], and vector control is essential to limiting disease spread. Because these arthropods ingest very large amounts of blood, a protein-rich meal, huge amounts of amino acids are produced during digestion. Previous work on Rhodnius prolixus, a vector of Chagas disease, showed that, among all amino acids, only tyrosine degradation enzymes were overexpressed in the midgut compared to other tissues [2]. Here we demonstrate that tyrosine detoxification is an essential trait in the life history of blood-sucking arthropods. We found that silencing Rhodnius tyrosine aminotransferase (TAT) and 4-hydroxyphenylpyruvate dioxygenase (HPPD), the first two enzymes of the phenylalanine/tyrosine degradation pathway, caused the death of insects after a blood meal. This was confirmed by using the HPPD inhibitor mesotrione, which selectively killed hematophagous arthropods but did not affect non-hematophagous insects. In addition, mosquitoes and kissing bugs died after feeding on mice that had previously received a therapeutic effective oral dose (1 mg/kg) of nitisinone, another HPPD inhibitor used in humans for the treatment of tyrosinemia type I [3]. These findings indicate that HPPD (and TAT) can be a target for the selective control of blood-sucking disease vector populations. Because HPPD inhibitors are extensively used as herbicides and in medicine, these compounds may provide an alternative less toxic to humans and more environmentally friendly than the conventional neurotoxic insecticides that are currently used, with the ability to affect only hematophagous arthropods.


Metabolic "Sense Relay" in Stem Cells: A Short But Impactful Life of PAS Kinase Balancing Stem Cell Fates.
Tissue regeneration is a complex molecular and biochemical symphony. Signaling pathways establish the rhythmic proliferation and differentiation cadence of participating cells to repair the damaged tissues and repopulate the tissue-resident stem cells. Sensory proteins form a critical bridge between the environment and cellular response machinery, enabling precise spatiotemporal control of stem cell fate. Of many sensory modules found in proteins from prokaryotes to mammals, Per-Arnt-Sim (PAS) domains are one of the most ancient and found in the most diverse physiological context. In metazoa, PAS domains are found in many transcription factors and ion channels; however, PAS domain-containing Kinase (PASK) is the only metazoan kinase where the PAS sensory domain is connected to a signaling kinase domain. PASK is predominantly expressed in undifferentiated, self-renewing embryonic and adult stem cells, and its expression is rapidly lost upon differentiation, resulting in its nearly complete absence from the adult mammalian tissues. Thus, PASK is expressed within a narrow but critical temporal window when stem cell fate is established. In this review, we discuss the emerging insight into the sensory and signaling functions of PASK as an integrator of metabolic and nutrient signaling information that serves to balance self-renewal and differentiation programs during mammalian tissue regeneration.


A novel ultra-performance liquid chromatography hyphenated with quadrupole time of flight mass spectrometry method for rapid estimation of total toxic retronecine-type of pyrrolizidine alkaloids in herbs without requiring corresponding standards.
Nearly 50% of naturally-occurring pyrrolizidine alkaloids (PAs) are hepatotoxic, and the majority of hepatotoxic PAs are retronecine-type PAs (RET-PAs). However, quantitative measurement of PAs in herbs/foodstuffs is often difficult because most of reference PAs are unavailable. In this study, a rapid, selective, and sensitive UHPLC-QTOF-MS method was developed for the estimation of RET-PAs in herbs without requiring corresponding standards. This method is based on our previously established characteristic and diagnostic mass fragmentation patterns and the use of retrorsine for calibration. The use of a single RET-PA (i.e. retrorsine) for construction of calibration was based on high similarities with no significant differences demonstrated by the calibration curves constructed by peak areas of extract ion chromatograms of fragment ion at m/z 120.0813 or 138.0919 versus concentrations of five representative RET-PAs. The developed method was successfully applied to measure a total content of toxic RET-PAs of diversified structures in fifteen potential PA-containing herbs.


Induction of plasminogen activator secretion in macrophages by electrochemical stimulation of the hexose monophosphate shunt with methylene blue.
Resident peritoneal macrophages were obtained from untreated mice and were cultured in medium 199 with or without 5% acid-treated fetal bovine serum. Three hours after harvesting, redox compounds--i.e., methylene blue, methyl viologen, or nitro blue tetrazolium--were added to the cultures of adherent cells. After 1 hr, the cells were washed and culturing was continued in the absence of redox compounds. The effects of the redox compounds were tested by assaying for hexose monophosphate (HMP) shunt activity and for plasminogen activator secretion, and the results were compared with the effects induced by phagocytic stimuli. Methylene blue caused a concentration-dependent stimulation of the HMP shunt, whereas methyl viologen and nitro blue tetrazolium were ineffective. Shunt stimulation by methylene blue was followed, after a lag of 2-4 days, by plasminogen activator secretion. The rate of secretion was dependent on the methylene blue concentration used. Methyl viologen and nitro blue tetrazolium were again ineffective, whereas phagocytosis of zymosan or sheep erythrocytes, which stimulates the HMP shunt, induced plasminogen activator secretion at rates similar to those induced by methylene blue. These results add further evidence to our hypothesis that the HMP shunt-dependent metabolic burst is involved in macrophage activation. Because methylene blue mimics the action of zymosan it appears that shunt stimulation by itself initiates the activation process independently of phagocytosis.


RACK1 regulates mesenchymal cell recruitment during sexual and asexual reproduction of budding tunicates.
A homolog of receptor for activated protein kinase C1 (RACK1) was cloned from the budding tunicate Polyandrocarpa misakiensis. By RT-PCR and in situ hybridization analyses, PmRACK1 showed biphasic gene expression during asexual and sexual reproduction. In developing buds, the signal was exclusively observed in the multipotent atrial epithelium and undifferentiated mesenchymal cells that contributed to morphogenesis by the mesenchymal-epithelial transition (MET). In juvenile zooids, the signal was first observable in germline precursor cells that arose as mesenchymal cell aggregated in the ventral hemocoel. In mature zooids, the germinal epithelium in the ovary and the pharynx were the most heavily stained parts. GFP reporter assay indicated that the ovarian expression of PmRACK1 was constitutive from germline precursor cells to oocytes. To elucidate the in vivo function of PmRACK1, RNA interference was challenged. When growing buds were incubated with 5 nmol/mL siRNA, most mesenchymal cells remained round and appeared to have no interactions with the extracellular matrix (ECM), causing lower activity of MET without any apparent effects on cell proliferation. The resultant zooids became growth-deficient. The dwarf zooids did not form buds or mature gonads. Prior to RNAi, buds were treated with human BMP4 that could induce PmRACK1 expression, which resulted in MET activity. We conclude that in P. misakiensis, PmRACK1 plays roles in mesenchymal cell recruitment during formation of somatic and gonad tissues, which contributes to zooidal growth and sexual and asexual reproduction.


Feasibility and characteristics of arterial stiffness measurement in preschool children.
Background Arterial stiffness is an important predictor of cardiovascular risk in adult life. Increased arterial stiffness can also be present in children and may be associated with several other cardiovascular risk factors. Until now, however, we know little about measuring arterial stiffness in preschool children. In this study, we assessed the feasibility of measuring arterial stiffness in preschool children and explored possible determinants related to arterial stiffness at this age. Methods We studied 168 healthy children, aged 3.3-4.1 years, who were recruited from a prospective birth cohort. We measured arterial stiffness, expressed in aortic pulse wave velocity and augmentation index, using a non-invasive oscillometric device (Arteriograph). We measured anthropometry and recorded other determinants using a questionnaire. Results In 100 children (59.5%) at least one valid arterial stiffness measurement was obtained. Of these infants, 89 had at least two valid measurements and 73 infants had at least three valid measurements. The mean aortic pulse wave velocity was 5.56 m/s (SD 0.77), and the mean augmentation index of the aorta was 19.7 m/s (SD 7.0). The augmentation index was significantly inversely associated with body height, with a regression coefficient of -0.78 (m/s)/cm (95% confidence interval -1.13 to -0.42). The augmentation index was not significantly associated with age, sex or (birth) weight. Conclusion The feasibility of measuring arterial stiffness in preschool children using the Arteriograph is moderate. We identified height as the most important determinant of the augmentation index in preschool children.


A review of evidence for GABergic predominance/glutamatergic deficit as a common etiological factor in both schizophrenia and affective psychoses: more support for a continuum hypothesis of "functional" psychosis.
Virtually all antidepressant and antipsychotic drugs, including clozapine, rimcazole and lithium ion, are proconvulsants, and convulsive therapy, using metrazol, a known GABA-A antagonist, as well as electro-convulsive therapy, can be effective in treating both schizophrenia and affective psychoses. Many antidepressant and antipsychotic drugs, including clozapine, as well as some of their metabolites, reverse the inhibitory effect of GABA on 35S-TBPS binding, a reliable predictor of GABA-A receptor blockade. A review of relevant literature suggests that 1) "functional" psychoses constitute a continuum of disorders ranging from schizophrenia to affective psychoses with overlap of symptoms, heredity and treatments, 2) a weakening of GABergic inhibitory activity, or potentiation of counterbalancing glutamatergic neurotransmission, in the brain, may be involved in the therapeutic activities of both antidepressant and antipsychotic drugs, and 3) schizophrenia and the affective psychoses may be different expressions of the same underlying defect: GABergic preponderance/glutamatergic deficit. Schizophrenia and affective psychoses share the following: 1) several treatments are effective in both, 2) similar modes of inheritance, 3) congruent seasonal birth excesses, 4) enlarged cerebral ventricles and cerebellar vermian atrophy, 5) dexamethasone non-suppression. Both genetic and environmental factors are involved in both schizophrenia and affective psychoses, and several lines of evidence suggest that important environmental factors are neurotropic pathogens that selectively destroy glutamatergic neurons. One group of genes associated with psychoses may increase vulnerability to attack and destruction, by neurotropic pathogens, of excitatory glutamatergic neurons that counterbalance inhibitory GABergic neurons. A second group of genes may encode subunits of overactive GABA-A receptors, while a third group of genes may encode subunits of hypo-active glutamate receptors. Improved antipsychotic drugs may be found among selective blockers of GABA-A receptor subtypes and/or enhancers of glutamatergic neurotransmission. A mechanism similar to kindling, leading to long-lasting reduction of GABergic inhibition in the brain, may be involved in several treatments of psychoses.


Dynamics of field-driven population inversion in a confined colloidal mixture.
We study, using Langevin dynamics simulations, the change in composition of a binary colloidal mixture confined in a finite-length channel, induced by an external field. The field-induced transition from a near-bulk composition to an inverted population is studied as a function of time, for different field strengths and system parameters. For state points corresponding to reversible field cycles, the cyclic filling and emptying of the channel by the minority species are compared. Extrapolation of the physical relaxation times to the colloidal regime is performed through a series of simulations at increasing value of the damping parameter. For state points at which the mixture is unstable at zero field, reproducible irreversible cycles are illustrated. For reversible field cycles, the scaling with the particles size of the characteristic cycling time is discussed.


Novel prognostic marker PRMT1 regulates cell growth via downregulation of CDKN1A in HCC.
Hepatocellular carcinoma (HCC) is a major type of liver cancer caused by the hepatitis B and C viruses, alcohol and exposure to aflatoxin. For HCC treatment, anticancer drugs have been widely used, but drug resistance in advanced HCC is an important problem, resulting in a continuous need for novel therapeutic targets. Therefore, in this study, we established a screening pipeline based on RNA-seq to screen novel therapeutic/prognostic targets in HCC and identified PRMT1 (Protein Arginine Methyltransferase 1). In the prognostic analysis, the overexpression of PRMT1 was clearly associated with poor prognosis in a number of HCC patient cohorts. Moreover, after PRMT1 knockdown, HCC cell lines exhibited cell growth and spheroid formation suppression, an increase in Sub-G1 cells by FACS analysis, and enrichment of the cell cycle pathway via functional enrichment analysis. With these results, we demonstrated that PRMT1 could be a novel prognostic marker and therapeutic target for HCC therapy.


Bridging PNAs can bind preferentially to a deleted mitochondrial DNA template but replication by mitochondrial DNA polymerase gamma in vitro is not impaired.
Mutations in mitochondrial DNA (mtDNA) are an important cause of neurological and other human pathologies. In the vast majority of cases, supportive care only is available. Mutated and wild-type mtDNAs often coexist in the same cell. A strategy for treatment has been proposed whereby replication of mutated mtDNA is inhibited by selective hybridisation of a nucleic acid derivative, allowing propagation of the wild-type genome and correction of the associated respiratory chain defect. Peptide nucleic acid molecules (PNAs) can be designed to selectively target pathogenic mtDNA with single point mutations. Molecules harbouring deletions present a complex problem. Deletions often occur between two short repeat sequences (4-13 residues), one of which is retained in the deleted molecule. With the more common large repeats, it is therefore difficult to design an antigenomic molecule that will bind selectively under physiological conditions. Following limited success with antigenomic oligodeoxynucleotides (ODNs), we have repeated these studies with a series of bridging PNAs. Molecules complementary to the sequence flanking either side of the 13 bp 'common deletion' were synthesised. The PNAs demonstrated markedly greater affinity for the delete than to the wild-type template. In runoff assays using Klenow fragment, these PNAs selectively inhibited replication of the delete template. However, no selective inhibition was observed when a polymerase gamma-containing mitochondrial fraction was used.


Children's literature in the school health education program.
Children's literature covers a wide range of topics, themes and issues that can help children in the elementary school health education program develop an awareness of personal and public health. A model for selecting and evaluating fictional stories and informational books that deal with topics included in the health education curriculum, giving particular attention to book selections that treat nutrition and environmental issues, is presented in this paper.


Sugammadex facilitates early recovery after surgery even in the absence of neuromuscular monitoring in patients undergoing laryngeal microsurgery: a single-center retrospective study.
In many countries, routine clinical anaesthesia does not always involve neuromuscular monitoring. In these clinical settings, the efficacy and safety of sugammadex use has not yet been confirmed. We investigated the efficacy and safety of sugammadex in the absence of neuromuscular monitoring. One hundred and forty patients who underwent laryngeal microsurgery with the use of rocuronium as a neuromuscular blocking agent, without the use of a neuromuscular monitoring device, were retrospectively investigated. The patients were randomly chosen among all the patients who met the inclusion criteria at a tertiary university hospital between July 2013 and February 2015 and were allocated to group S (sugammadex group) or group P (pyridostigmine group) according to the neuromuscular reversal agent administered. Five patients were excluded from analysis and 135 patients completed the study. Primary outcome was extubation time. Secondary outcomes were anaesthesia time, the correlation between anaesthesia time and extubation time, the total amount of rocuronium, and postoperative adverse events in the post-anaesthesia care unit (PACU). Extubation time was significantly shorter in group S (6.3 ± 3.9 min) than in group P (9.0 ± 5.4 min). Anaesthesia time was also significantly shorter in group S (30.7 ± 10.3 min) than in group P (35.8 ± 12.6 min). In the patients with an anaesthesia time of 30 min or less, there was a positive correlation between anaesthesia time and extubation time in group P (r = 0.453), but there was no significant relationship in group S. The total amount of rocuronium used was higher in group S (0.62 ± 0.11 mg kg(-1)) than in group P (0.38 ± 0.14 mg kg(-1)). Postoperative adverse events in the PACU were comparable between the groups, except for tachycardia events: the incidence of tachycardia was significantly lower in group S (8.0 %) than in group P (17.3 %). Sugammadex could shorten anaesthesia and extubation times as well as recovery time in the PACU and reduce postoperative hemodynamic complications in a clinical setting in the absence of neuromuscular monitoring. This may enhance the patients' recovery in the operating room and PACU while improving the postoperative condition of patients. The trial was registered in the UMIN clinical trials registry ( www.umin.ac.jp/ctr/index/htm ; unique trial number: UMIN000016602; registration number: R000019266 ; principal investigator's name: Byung Gun Lim; date of registration: February 22, 2015).


Tissue-mediated selection of viral variants: correlation between glycoprotein mutation and growth in neuronal cells.
Viral variants with different biological properties predominate in the central nervous system (CNS) and lymphoid tissues of carrier mice infected at birth with the Armstrong strain of lymphocytic choriomeningitis virus. The CNS isolates have the same phenotype as the parental strain and cause acute infections in adult mice, while the spleen-derived isolates cause chronic infections associated with suppressed T-cell responses and susceptibility to opportunistic infections. Our previous studies have identified a single amino acid change in the viral glycoprotein, a phenylalanine-to-leucine (F-->L) mutation at residue 260, that correlates with the tissue-specific selection and the persistent and immunosuppressive phenotype of the spleen isolates (R. Ahmed, C.S. Hahn, T. Somasundaram, L. Villarete, M. Matloubian, and J. H. Strauss, J. Virol. 65:4242-4247, 1991). In this study, we screened viral isolates obtained from the spleen, liver, kidney, and brain of carrier mice for the presence of this mutation and determined the temporal selection of variants as they appear in these organs. We found that this F-->L amino acid change is common to > 90% of the spleen and liver isolates and is selected for rapidly by day 32 postinfection (p.i.). Although the kinetics observed in the kidney are relatively slower than in the spleen and liver, this F-->L mutation predominates in the kidney-derived isolates by 250 days p.i. In contrast, the majority of the CNS isolates retain the parental sequence up to 250 days p.i. In addition, most of the brain isolates replicated efficiently in a neuronal cell line, and this enhanced growth phenotype in neurons correlated with the parental F genotype. This linkage with neurotropism, along with our earlier finding that the F-->L mutation is necessary for enhanced infection of macrophages (M. Matloubian, S. R. Kolhekar, T. Somasundaram, and R. Ahmed, J. Virol. 67:7340-7349, 1993), provides a cellular basis for the molecular changes associated with tissue-specific selection. Taken together, these results suggest that tropism for macrophages is a critical determinant in selection of variants with the F-->L mutation in tissues such as spleen and liver, and tropism for neurons is important in retention of the F genotype in the CNS.


Impact of a pharmacy technician-centered medication reconciliation program on medication discrepancies and implementation of recommendations.
To evaluate the impact of a pharmacy-technician centered medication reconciliation (PTMR) program by identifying and quantifying medication discrepancies and outcomes of pharmacist medication reconciliation recommendations. A retrospective chart review was performed on two-hundred patients admitted to the internal medicine teaching services at Cooper University Hospital in Camden, NJ. Patients were selected using a stratified systematic sample approach and were included if they received a pharmacy technician medication history and a pharmacist medication reconciliation at any point during their hospital admission. Pharmacist identified medication discrepancies were analyzed using descriptive statistics, bivariate analyses. Potential risk factors were identified using multivariate analyses, such as logistic regression and CART. The priority level of significance was set at 0.05. Three-hundred and sixty-five medication discrepancies were identified out of the 200 included patients. The four most common discrepancies were omission (64.7%), non-formulary omission (16.2%), dose discrepancy (10.1%), and frequency discrepancy (4.1%). Twenty-two percent of pharmacist recommendations were implemented by the prescriber within 72 hours. A PTMR program with dedicated pharmacy technicians and pharmacists identifies many medication discrepancies at admission and provides opportunities for pharmacist reconciliation recommendations.


PHA665752 inhibits the HGF-stimulated migration and invasion of cells by blocking PI3K/AKT pathway in uveal melanoma.
HGF/c-MET is frequently associated with tumor metastasis in many cancers, including uveal melanoma (UM). PHA665752, a selective c-MET inhibitor, exhibits anticancer activity through inhibiting cell motility in some cancers. In this study, we investigated the effects of PHA665752 on UM cell lines M17 and SP6.5. Our data show that HGF stimulated the motility of UM cells, and induced the activation of both c-MET and PI3K/AKT, but not ERK1/2. Moreover, consistent with the amount of c-MET within the nucleus, PHA665752 significantly inhibited HGF-promoted cell motility and suppressed the phosphorylation of c-MET and PI3K/AKT, but not ERK1/2 induced by HGF. Additionally, the effects of PHA665752 on both the inhibition of HGF-induced cell motility and the suppression of active AKT are similar to those of PI3K inhibitor LY294002. In xenograft models, PHA665752 significantly inhibited tumor growth in nude mice and similarly suppressed the phosphorylation of c-MET and PI3K/AKT. Our current findings, combined with previous results, demonstrate that PHA665752 inhibits HGF-induced motility via the inhibition of PI3K/AKT. This study suggests that targeting HGF/c-MET could be a promising therapeutic strategy for UM by preventing cell motility.


Isolated pontine infarction due to rhinocerebral mucormycosis.
We report a patient with rhinocerebral mucormycosis whose initial central nervous system involvement was isolated pontine infarction due to basilar arteritis caused by the fungus. The patient was diagnosed and followed by MRI and CT and basilar arteritis was demonstrated well on MRI studies. Involvement of the skull base was shown on CT in the later stage of the disease. The unusual initial presentation of the infection is discussed.


Variables influencing the ratings of importance and use of quality of life domains and indicators by Polish professionals.
Interest in the concept of quality of life (QOL) as a category guiding the development and provision of services for individuals with intellectual disabilities (ID) in Poland is increasingly being observed. Its presence in rehabilitation and care is strongly associated with the assessment of importance and use of QOL domains and indicators by Polish professionals. The present study examined the differences related to selected demographic variables in the assessment of importance and use of eight QOL domains made by professionals in Poland working with persons with ID. The evaluation of the importance and use of eight QOL domains and their indicators is related significantly to professionals' level of education, place of work, and total years of work. The perception of professionals cannot be overlooked when considering the development and provision of QOL-related services and supports.


Effects of chronic stress on hippocampal long-term potentiation.
Chronic stress causes atrophy of the apical dendrites of CA3 pyramidal neurons and deficits in spatial memory. We investigated the effects of chronic stress on hippocampal physiology and long-term potentiation (LTP) in the CA3 and dentate gyrus (DG). Rats were subjected to chronic (21 days, 6 h/day) restraint stress and tested for LTP 48 h following the last stress episode. Control animals were briefly handled each day, similar to the experimental group but without restraint. To eliminate acute stress effects, a second control group of rats was subjected to a single acute (6 h) restraint stress and tested for LTP 48 h later. Field potential recordings were made, under chloropent anesthesia, from the stratum lucidum of CA3, with stimulation of either the mossy fiber or commissural/associational pathways, or in the DG granule-cell layer, with stimulation of the medial perforant pathway. Chronic stress produced a suppression of LTP at 48 h compared to controls in a site-specific manner, namely, significantly lower LTP in the medial perforant input to the DG and also in the commissural/associational input to the CA3, but not in the mossy fiber input to CA3. The animals subjected to acute stress and tested 48 h later did not show a suppression in LTP. High-frequency stimulation (HFS) of the commissural/associational and mossy fiber inputs to CA3 produced epileptic afterdischarges in 56% of acutely stressed animals and in 29% of chronically stressed animals, whereas HFS caused afterdischarges in only 9% of nonstressed controls. No afterdischarges were seen in the medial perforant path input to DG. In order to explore the basis for these changes, we performed paired-pulse inhibition/facilitation (PPI/F) and current-source-density (CSD) analysis in stressed and control animals. For PPI/F, acute stress caused an overall significant enhancement of excitation in the commissural/associational input to CA3 and medial perforant path input to DG. In contrast, chronic stress did not produce significant changes in PPI/F. The CSD analysis revealed significant chronic stress-induced shifts in the current sources and sinks in the apical dendrites and pyramidal cell layers of the CA3 field but not in the DG. These results are consistent with the morphological findings for stress effects upon dendrites of CA3 neurons. Furthermore, they suggest that chronic stress produces changes in the input-output relationship in the hippocampal trisynaptic circuit which could affect information flow through this structure.


Na/K-ATPase Signaling and Salt Sensitivity: The Role of Oxidative Stress.
Other than genetic regulation of salt sensitivity of blood pressure, many factors have been shown to regulate renal sodium handling which contributes to long-term blood pressure regulation and have been extensively reviewed. Here we present our progress on the Na/K-ATPase signaling mediated sodium reabsorption in renal proximal tubules, from cardiotonic steroids-mediated to reactive oxygen species (ROS)-mediated Na/K-ATPase signaling that contributes to experimental salt sensitivity.


Validation of a sensitive LC/MS/MS method for simultaneous quantitation of flupentixol and melitracene in human plasma.
A sensitive method has been developed and validated, using LC/ESI-MS/MS, for simultaneous quantitation of flupentixol and melitracen--antidepressant drugs, in human plasma. The quantitation of the target compounds was determined in a positive ion mode and multiple reaction monitoring (MRM). The method involved a repeated liquid-liquid extraction with diethyl ether and analytes were chromatographed on a C(8) chromatographic column by elution with acetonitrile-water-formic acid (36:64:1, v/v/v) and analyzed by tandem mass spectrometry. The method was validated over the concentration ranges of 26.1-2090 pg/ml for flupentixol and 0.206-4120 ng/ml for melitracen. The correlation coefficients of both analyst were >0.998 for six sets of calibration curves. The recovery was 60.9-75.1% for flupentixol, melitracen and internal standard. The lower limit of quantitation (LLOQ) detection was 26.1 pg/ml for flupentixol and 0.206 ng/ml for melitracen. Intra- and inter-day precision of the assay at three concentrations were 2.15-5.92% with accuracy of 97.6-103.0% for flupentixol and 0.5-6.36% with accuracy of 98.7-101.7% for melitracen. Stability of compounds was established in a battery of stability studies, i.e., bench-top, autosampler and long-term storage stability as well as freeze/thaw cycles. The method proved to be suitable for bioequivalence study of flupentixol and melitracen in healthy human male volunteers.


Novel IMPG2 variant causing adult macular vitelliform dystrophy: A case report.
Adult-onset vitelliform macular dystrophy (AVMD) is an inherited maculopathy characterized by metamorphopsias and decrease in visual acuity occurring between the fourth and the sixth decade. It is characterized by an 'egg yolk' macular lesion eventually evolving towards foveal atrophy and fibrosis. It is usually an autosomal dominant inherited disorder with variable penetrance, mainly related to variants in BEST1, PRPH2, IMPG1, and IMPG2 genes. A 47-year-old woman complaining of "wavy" vision was referred to our clinic. Her past medical history and reported family history did not reveal any ocular disease. Complete ophthalmological evaluation was performed. Funduscopic examination and multimodal imaging revealed a round vitelliform lesion in both eyes, leading to a diagnosis of AVMD. Genetic analysis revealed a novel, likely pathogenetic, heterozygous c.478G > T (p.Glu160Ter), (NM_016247) variant in the IMPG2 gene. Our patient exhibits a novel pathogenetic variant in a gene associated with AVMD. Heterozygous variants in the IMPG2 gene have been reported in multiple individuals with vitelliform macular dystrophy, with an autosomal dominant mode of inheritance. Genetic screening is essential to characterize patients, to predict vision loss in patients with a positive family history and to characterize eligible patients for new potential emerging therapies. Genotype-phenotype correlation studies are needed to have a clearer picture of pathogenetic mechanisms. Our study characterizes the phenotype related to a novel IMPG2 pathogenic variant through multimodal imaging.


Inhibition of the p66/p51 form of human immunodeficiency virus reverse transcriptase by tRNA(Lys).
Human immunodeficiency virus (HIV) reverse transcriptase (RT) uses host tRNA(Lys) partially annealed to the primer binding site (PBS) as primer for the initiation of cDNA synthesis. When assaying cDNA synthesis with a template-primer complex formed by an RNA fragment carrying the PBS site and bovine tRNA(Lys) we noticed that an excess of primer tRNA inhibited strongly the DNA polymerase activity of a recombinant HIV RT (p66-p51 heterodimeric form) produced in transformed yeast cells. The same inhibitory effect was observed with animal DNA polymerase alpha, while avian retrovirus RT was neither affected by tRNA(Lys) nor by its specific primer tRNA(Trp). Although the strongest inhibition was observed with tRNA(Lys), other tRNas like tRNA(Phe) and tRNA(Trp) inhibited also the HIV RT, whereas tRNAs specific for valine, proline and glycine had no effect on enzyme activity. Digestion of tRNA(Lys) with pancreatic RNase abolished the inhibition; on the other hand T1 RNase digestion had no effect on the inhibition suggesting a role of the anticodon region in this effect. The 12- and 14-mers corresponding to the anticodon regions of the three bovine tRNA(Lys) isoacceptors inhibited RT activity, indicating that at least an important part of the inhibitory effect could be ascribed to this tRNA region. A strong stimulation of DNA polymerase activity was observed when the effect of tRNA(Lys) was assayed on a recombinant HIV reverse transcriptase produced in a protease deficient yeast strain, which leads to the production of an active p66 enzyme. The same tRNAs that inhibited strongly the heterodimeric form stimulated the p66 form of HIV reverse transcriptase. The results suggest that although both enzymatic forms are able to interact with tRNA(Lys) the topography, as well as the functional implications of the interaction between the precursor and the mature form of HIV reverse transcriptase with the tRNA(Lys) primer, are different.


Arquivos de Neuro-Psiquiatria: 75 years.
This year marks the 75th year of publication of Arquivos de Neuro-Psiquiatria (ANP), the official journal of the Brazilian Academy of Neurology and one of the most important neuroscience journals in Latin America. ANP was initially edited by Oswaldo Lange, its founder, and subsequently by Antonio Spina-França Netto and, in recent years, by José Antonio Livramento and Luís dos Ramos Machado.


Peripheral arteries in diabetic patients: standard bolus-chase and time-resolved MR angiography.
To prospectively determine the diagnostic performance of a combination of standard bolus-chase magnetic resonance (MR) angiography and MR angiography with time-resolved imaging of contrast kinetics (TRICKS) for depicting severity of peripheral vascular disease of the lower extremity, including the pedal arteries, in diabetic patients with digital subtraction angiography (DSA) as the reference standard. An ethical committee approved this study; written informed consent was obtained from patients. Standard three-station and TRICKS MR angiography of the calf and foot were performed in 31 consecutive diabetic patients (23 men, eight women; mean age, 67 years; range, 43-81 years). Two readers separately assessed images of arterial segments as diagnostic or nondiagnostic and graded stenosis. Results were compared with those at DSA when the corresponding arterial segments were considered diagnostic at DSA. Wilcoxon signed rank test was used to determine if a significant difference between imaging techniques existed, and kappa statistics were used to determine interobserver agreement. The difference between standard MR angiography and DSA regarding the number of diagnostic segments in the thigh was not significant (P = .50). A significantly higher number of calf and foot segments was considered diagnostic at TRICKS MR angiography than at standard MR angiography (P < .025). Sixteen of 26 segments in the foot that were considered nondiagnostic at DSA were considered diagnostic at TRICKS MR angiography. Average sensitivity of standard MR angiography for depicting hemodynamically significant arterial stenosis was 84% (reader 1) and 83% (reader 2) in the thigh and 78% (reader 1) and 80% (reader 2) in the calf. For both readers, average specificity was 97% in the thigh and 90% in the calf. Sensitivity and specificity of TRICKS MR angiography in the calf and foot were improved compared with those at standard MR angiography. TRICKS MR angiography of the distal calf and pedal vessels is superior to standard MR angiography regarding the number of diagnostic segments and assessment of the degree of luminal narrowing.


Pancreatic trauma.
The early diagnosis of pancreatic injuries depends on a high degree of clinical suspicion. During laparotomy, exploration of the pancreas and duodenum for suspected injury should be thorough and orderly. In managing these injuries, one should select the simplest procedure that will re-establish the integrity of the upper gastrointestinal tract and control the free escape of pancreatic juices into the surrounding tissue. In general, resection of the distal portion of the body and tail of the pancreas for severe injuries in that area and duodenal diverticularization for injuries involving the pancreatic head are the procedures of choice for preservation of functioning pancreatic tissue.


A new method of inhalation anesthesia with nasopharyngeal insufflation in rat experiment.
We have established a new method of anesthesia with nasopharyngeal insufflation for intraoral procedure in rodents. Twelve male Wistar rats weighing 330-390 g were used in this study. Insertion of a feeding tube 1.0 mm in diameter coated with 2% xylocaine jelly was inserted into the nasal cavity approximately 25 mm from the naris, and anesthetization with mixed gas of 100% oxygen with 3-4% enflurane at 0.25-0.5 l/min flow rate was achieved. Using this anesthetic method, a chronic experiment comprising 1-h/day experimental procedure was carried out for 14 days. This method enabled, 1) simple and safe operation of the induction, emergence and anesthetic depth, 2) experimental procedures on the dental/oral region, 3) avoidance of the dyspnea and tachypnea, and 4) avoidance of cumulative effects in daily anesthesia.


[Microsurgical modification of Allen's glaucoma operation].
The modified anti-glaucomatous operation, introduced its classical version by Allen, has been presented in this paper. The microsurgical version could be defined as micro-cyclodialysis with basal iridectomy, combined with the restoration of the anterior chamber. The surgery was performed in simple glaucoma and glaucoma in aphakic eyes. The details of the surgery and the illustrations of its respective phases have been presented. The results were based on clinical observation of 41 patients. The satisfactory results, up to 6 months, were obtained in 85.3% of the patients. Later the percentage decreases to 78%. For 10 aphakic eyes stabilization was obtained in 9 cases.


A nationwide evaluation study of the quality of care and respect of human rights in mental health facilities in Ghana: results from the World Health Organization QualityRights initiative.
In 2012, Ghana ratified the United Nations Convention on the Rights of Persons with Disabilities and enacted a Mental Health Act to improve the quality of mental health care and stop human rights violations against people with mental health conditions. In line with these objectives, Ghanaian stakeholders collected data on the quality of mental health services and respect for human rights in psychiatric facilities to identify challenges and gather useful information for the development of plans aimed to improve the quality of the services offered. This study aimed to assess psychiatric facilities from different Ghanaian regions and provide evidence on the quality of care and respect of human rights in mental health services. Assessments were conducted by independent visiting committees that collected data through observation, review of documentation, and interviews with service users, staff, and carers, and provided scores using the World Health Organization QualityRights Toolkit methodology. This study revealed significant key challenges in the implementation of the United Nations Convention on the Rights of Persons with Disabilities principles in Ghanaian psychiatric services. The rights to an adequate standard of living and enjoyment of the highest attainable standard of health were not fully promoted. Only initial steps had been taken to guarantee the right to exercise legal capacity and the right to personal liberty and security. Significant gaps in the promotion of the right to live independently and be included in the community were identified. This study identifies shortcomings and critical areas that the Ghanaian government and facilities need to target for implementing a human rights-based approach in mental health and improve the quality of mental health care throughout the country.


Myosteatosis in adolescents and young adults treated for acute lymphoblastic leukemia.
Myosteatosis refers to fat deposition within muscle and is linked to risk of cardiovascular disease and metabolic disorders. Though these comorbidities are common during and after therapy for acute lymphoblastic leukemia (ALL), little is known about tissue distribution, including myosteatosis, in this population. Using quantitative computed tomography, we assessed the impact of ALL therapy on bone, muscle, subcutaneous, and muscle-associated (MA) fat in 12 adolescents and young adults (AYA) treated for ALL as compared to a healthy control group without ALL (n = 116). AYA had a marked loss of muscle with a gain in MA fat between ALL diagnosis and end of induction. These changes persisted throughout intensive therapy. Lower bone and muscle and higher MA fat were also observed during and after treatment in comparison to controls. Altered lower extremity tissue distribution, specifically myosteatosis and sarcopenia, may contribute to functional declines and increased risk of metabolic disorders and cardiovascular diseases.


Bacille Calmette-Guérin vaccination is associated with lower prevalence of allergic diseases in Indian children.
Immunization with bacille Calmette-Guérin (BCG) has been shown to augment T helper (Th) 1 biased response and hence gives protection against developing allergies. However, results across the studies have been inconclusive and there is no Indian study verifying this association. We explored the link between BCG vaccination and prevalence of allergic diseases among school children of Chandigarh, North India. In a large cross-sectional study, children aged 7-14 years, with and without documentation and/or scar consistent with BCG vaccination, were examined over a period of 2 years and 5 months with the help of a questionnaire-based survey followed by skin-prick test (SPT). A total of 10,028 children were included. The mean age was 11.04 ± 2.8 years and M/F ratio was 1.1:1. Among them, 77.7% had documentation of BCG vaccination, 17% had a BCG-like scar but no documentation and 5.3% had no scar/documentation. SPT was performed on 1614 (16%) children. In the BCG group (vaccination and/or scar) 16.7% were atopic (positive SPT) compared with 21.3% in no BCG (no vaccination/scar). The prevalence of allergic diseases among BCG(+) subjects was 10.1%. Among these, asthma was the commonest one (6.1%), followed by rhinitis (3.5%) and eczema (0.5%). There was significant negative correlation between BCG positivity, atopy (p = 0.037), and allergic diseases as a whole (p = 0.028), but on independent analysis the negative correlation was strongest with allergic rhinitis (p = 0.011). BCG vaccination is associated with lower prevalence of allergic disorders in Indian children.


Hepatic basolateral sodium-dependent-bile acid transporter expression in two unusual cases of hypercholanemia and in extrahepatic biliary atresia.
The recent cloning of a human sodium-dependent bile acid transporter (NTCP) permits analysis of its expression in human liver disease and investigation of potential primary defects in its expression. NTCP from normal human liver (NHL) was first characterized in detail. Northern blotting of RNA from NHL revealed a 1.8-kb NTCP transcript. Western blotting of crude NHL plasma membranes using a carboxyterminal antipeptide antibody showed that NTCP is a 39-kd polypeptide that is N-glycosylated to a final molecular weight of 56 kd. Indirect immunofluorescent analysis of NHL sections indicated that the NTCP protein is expressed on the basolateral surface of hepatocytes. We hypothesized that the clinical phenotype of a defect in NTCP might be hypercholanemia in the relative absence of liver disease. Accordingly, the coding region of the NTCP gene of two children with this phenotype was sequenced after reverse transcription/polymerase chain reaction (RT/PCR) amplification. No primary defects in the deduced NTCP amino acid sequence were found. Despite the extremely high serum bile salt levels (235 and 126 micromol/L) in these two patients, NTCP messenger RNA (mRNA) and protein expression were quantitatively normal, in contrast to the published observations in a rat model of cholestasis secondary to common bile duct ligation. Hepatic steady-state NTCP mRNA levels in a group of 23 pre- and postportoenterostomy biliary atresia patients were inversely related to total bilirubin, indicating that extrahepatic bile duct obstruction leads to down-regulation of NTCP mRNA levels, similar to that observed in rat common bile duct ligation. Therefore the lack of down-regulation in the two patients with hypercholanemia indicates that elevated serum bile salts are not sufficient to down-regulate NTCP expression, these two patients have abnormal responses to hypercholanemia, or these two patients have a defect in a gene other than NTCP that influences hepatic clearance of bile salts.


Plant-water relations and the fibre saturation point.
This review is about the behaviour of water in cell walls. The aim is to introduce to biologists the concept of the fibre saturation point (FSP), and the related research of material scientists and engineers on the thermodynamics and chemistry of water in timber and wood. In the review, we first summarise what the FSP is, why it is important and how the FSP is routinely used by engineers and material scientists to estimate the volume fractions of solid, liquid and gas phases in bulk timber. We then show that the FSP can be intuitively understood using equilibrium thermodynamics. That analysis shows that the FSP is based on the concept that a certain (and repeatable) amount of water is chemically bound to cellulose and other substances in wood. That water, sometimes called bound water, exists in a water-cell wall mixture. The noted physical chemist and wood scientist, A. J. Stamm, called this mixture a 'solid solution'. In timber, the 'solid solution' is considered a separate phase from adjacent water in either a pure liquid phase or a vapour phase. Following that, we examine the FSP and wood-water dynamics at the molecular and cellular level. Despite differences between timber and living trees, we conclude that the FSP-based framework long used by material scientists and engineers is likely to be useful to biologists.


Hypercomplementemia at relapse in patients with anti-aquaporin-4 antibody.
Because Asian patients with opticospinal multiple sclerosis (OSMS) frequently have anti-aquaporin-4 (AQP4) antibody, complement-mediated disruption of astrocyte foot processes is proposed but not yet proven. We aimed to clarify whether complement consumption occurs at relapse in anti-AQP4 antibody-positive patients. We analyzed serum CH50, C3, C4, and C-reactive protein (CRP) levels and their relation to clinical phases in 118 MS patients with or without anti-AQP4 antibody. Serum CH50 levels were higher in 24 patients with anti-AQP4 antibody than in 39 OSMS and 54 conventional form of MS (CMS) patients without anti-AQP4 antibody at relapse (Pcorr<0.05) but not in remission. The frequency of hypercomplementemia at relapse was also higher in anti-AQP4 antibody-positive patients than in anti-AQP4 antibody-negative CMS patients (70.4% vs 29.0%, Pcorr<0.05). C3 and C4 levels did not differ significantly among the three groups at relapse. In patients with anti-AQP4 antibody, the coexistence of hypercomplementemia and high CRP values was more common at relapse than in the remission phase (36.0% vs 10.5%, P<0.05). In patients with extensive central nervous system lesions, hypercomplementemia was significantly more common in anti-AQP4 antibody-positive patients than anti-AQP4 antibody-negative ones (88.9% vs 16.7%, P<0.01). We consider that hypercomplementemia in anti-AQP4 antibody-positive patients may reflect a systemic inflammatory reaction at relapse.


Incremental mutual information: a new method for characterizing the strength and dynamics of connections in neuronal circuits.
Understanding the computations performed by neuronal circuits requires characterizing the strength and dynamics of the connections between individual neurons. This characterization is typically achieved by measuring the correlation in the activity of two neurons. We have developed a new measure for studying connectivity in neuronal circuits based on information theory, the incremental mutual information (IMI). By conditioning out the temporal dependencies in the responses of individual neurons before measuring the dependency between them, IMI improves on standard correlation-based measures in several important ways: 1) it has the potential to disambiguate statistical dependencies that reflect the connection between neurons from those caused by other sources (e.g. shared inputs or intrinsic cellular or network mechanisms) provided that the dependencies have appropriate timescales, 2) for the study of early sensory systems, it does not require responses to repeated trials of identical stimulation, and 3) it does not assume that the connection between neurons is linear. We describe the theory and implementation of IMI in detail and demonstrate its utility on experimental recordings from the primate visual system.


Nickel-Catalyzed Direct Cross-Coupling of Unactivated Aryl Fluorides with Aryl Bromides.
A nickel-catalyzed direct cross-coupling of unactivated aryl fluorides with aryl bromides is realized. The one-pot reaction, which avoids the use of preformed and sensitive organometallic reagents, proceeds effectively via C-F bond cleavage at room temperature in THF in the presence of the phosphine ligand and magnesium powder (with or without TMSCl) to produce the desired biaryls in modest to good yields.


A Ten-year Report of Drug and Poison Information Center in Mashhad, Iran 2007-2017.
The Mashhad drug and poison information center (MDPIC) was officially established in 2000 to provide up-to-date information on medications. The objective of this study is to provide an epidemiologic profile of drug inquiry and poisoning-related phone calls to MDPIC from 2007 to 2017. This article is a descriptive retrospective study in which all inquiries about drugs and poisoning cases received by MDPIC, from 1st January 2007 to 31st December 2017, were retrieved from its database for analysis. A total of 100997 cases were analyzed. The most frequent calls were from individuals in the age group of 18 to 60 years old (70.21%). The majority of callers were women (73.08%). The public made 95.11% of calls, and 4.89% were related to health care professionals. The queries were mainly related to therapeutic uses of drugs (24.03%), followed by adverse drug reactions (18.96%). Given that 99.23% of calls were related to drug information inquiries, the most common drugs questioned about were antimicrobial (12.3%) and vitamin and minerals (10.76%), whereas 0.77% of calls were about poisoning and the majority of them were due to drugs poisoning. Micromedex® was the most commonly used reference to answer the inquiries. This report shows an updated epidemiological evaluation on recorded calls in the drug and poison information center in Mashhad. Since there is no other similar report, this can provide valuable information on the trend of drug usage and may guide further strategies in giving proper information to public and health centers.


Body mass index and fat patterning of adults in rural Sarawak.
Body fatness distribution is a useful epidemiological and clinical marker of health risk among European and other populations. Prevalence of obesity among adults is rising in many parts of Malaysia, and it is important to understand the extent to which fat patterning is robust across different age groups and between the sexes. This analysis examines fatness and fat distribution in rural Sarawakian adults aged 20 to 80 years to determine the extent to which fat patterning varies by sex and age. Principal component analysis of five skinfolds (biceps, triceps, subscapular, suprailiac and medial calf) shows upper body-lower body fat distribution as contributing most to within-group variation in the sum of five skinfolds for both males and females. When divided into younger and older age groups, clear differences were identified. For the males, while absolute fatness does not change with age, there is a change in fat patterning, with a trunk-extremity component disappearing, and a trunk-lower body pattern persisting. Females experience a decline in subcutaneous fatness across age groups, and while the most important component of fat distribution, trunk to lower body subcutaneous fatness, the same for younger and older women, the second component is different, with upper limb-lower body distribution in the younger age group being replaced with upper to lower trunk distribution. The similarities in fat patterning among males and females suggest that the use of fat patterning indices in this Malaysian population need not be sex-specific, but age group- and sex-dependent differences in the second principal component indicate that they should be used with caution, since the relationships between fat patterning and mortality are still poorly understood among Malaysian populations.


Measuring scattering light distributions on high-absorptive surfaces for stray-light reduction in gravitational-wave detectors.
In order to establish scattering measurements in material investigations for gravitational-wave detectors, we have built-up devices for measuring the hemispherical scattering distribution of materials which are planned to be used in those detectors as suppressors of scattered light. The measurement benches we have built, a hemispherical goniometer and a direct back-scatterometer, have a maximum background noise of ∼10 -4sr -1 BRDF at 1.064 μm wavelength which is the wavelength of the laser-light for our large interferometer for detecting gravitational waves, KAGRA. With these instruments, we have characterized the surface scattering of, e.g., NiP platings, metals, and different carbonaceous coatings, which are supposed to minimize the amount of scattered light in interferometers. The three most important materials for KAGRA's construction (SiC, "Solblack", and "VantaBlack") are presented in this paper. Furthermore, we will try to explain the scattering distributions with the generalized Harvey-Shack model (smooth-surface approximation) which is a common method for surface-scattering calculations. At the end, we give also some valuations about the vacuum compatibility of the materials, which is important for instruments like KAGRA that work under ultra-high vacuum conditions.


Optimal Path of Internet of Things Service in Supply Chain Management Based on Machine Learning Algorithms.
With the development of global economic integration, the scale of supply chain network is becoming larger and larger. The research on the benefits of supply chain network under the Internet of Things technology is a new interdisciplinary research issue. Starting from the complexity and evolution of supply chain network, based on machine learning algorithms, this study analyses the service modes of the Internet of Things for supply chain enterprises, such as RFID technology, EDI technology, and enterprise resource planning ERP. Finally, by analyzing the degree of application of the Internet of Things in different industries, the manufacturing industry is selected for simulation. It is found that the introduction of the Internet of Things is conducive to speeding up the evolution of enterprise supply chain. Thus, the horizontal integration of the optimized path supply chain can effectively improve the overall profits of enterprises and provide theoretical support for the Internet of Things service supply chain.


Cellular and molecular characterisation of the ovine rectal mucosal environment.
Immunohistological characterisation of ovine rectal tissue has revealed the presence of lymphoid follicles, predominantly in the submucosa, that closely resemble those found in intestinal Peyer's patches (PPs). Distinct T (CD4+, CD8+, gammadelta-TCR+) and B (CD21+, CD45R+) lymphocyte staining patterns were observed within and around follicles of the rectal mucosa. In addition, IgA+ and IgE+ cells were also found at this tissue site, with both phenotypes commonly residing in the lamina propria. RT-PCR examination of the cytokines expressed in the rectal mucosal tissue revealed consistently high levels of TGFbeta and IL-8 mRNA, low levels of IL-2 mRNA and no detectable IL-4 mRNA. The presence of lymphoid follicles, IgA+ plasma cells and IgA-inducing cytokines in rectal tissue of sheep indicate that this may be a suitable route for delivering mucosal vaccines.


Aza-Henry Reactions on C-Alkyl Substituted Aldimines.
The reactivity of C-CH₃ substituted N-protected aldimines in aza-Henry addition reactions was compared with that of the analogous trifluoromethylated compounds. C-Alkyl aldimines easily reacted with nitro alkanes under solvent-free conditions and in the absence of catalyst, despite being worse electrophiles than C-CF₃ aldimines, they gave the aza-Henry addition only when ZrCl₄ was added. The presence of a bulky group on the imine carbon deeply influenced the reactivity.


Benefits of combined GPS/GLONASS with low-cost MEMS IMUs for vehicular urban navigation.
The integration of Global Navigation Satellite Systems (GNSS) with Inertial Navigation Systems (INS) has been very actively researched for many years due to the complementary nature of the two systems. In particular, during the last few years the integration with micro-electromechanical system (MEMS) inertial measurement units (IMUs) has been investigated. In fact, recent advances in MEMS technology have made possible the development of a new generation of low cost inertial sensors characterized by small size and light weight, which represents an attractive option for mass-market applications such as vehicular and pedestrian navigation. However, whereas there has been much interest in the integration of GPS with a MEMS-based INS, few research studies have been conducted on expanding this application to the revitalized GLONASS system. This paper looks at the benefits of adding GLONASS to existing GPS/INS(MEMS) systems using loose and tight integration strategies. The relative benefits of various constraints are also assessed. Results show that when satellite visibility is poor (approximately 50% solution availability) the benefits of GLONASS are only seen with tight integration algorithms. For more benign environments, a loosely coupled GPS/GLONASS/INS system offers performance comparable to that of a tightly coupled GPS/INS system, but with reduced complexity and development time.


Coverage and beliefs about temephos application for control of dengue vectors and impact of a community-based prevention intervention: secondary analysis from the Camino Verde trial in Mexico.
Temephos in domestic water containers remains a mainstay of Latin American government programmes for control of Aedes aegypti and associated illnesses, including dengue. There is little published evidence about coverage of routine temephos programmes. A cluster randomised controlled trial of community mobilisation in Mexico and Nicaragua reduced vector indices, dengue infection, and clinical dengue cases. Secondary analysis from the Mexican arm of the trial examined temephos coverage and beliefs, and the impact of the trial on these outcomes. The trial impact survey in December 2012, in 10,491 households in 45 intervention and 45 control clusters, asked about visits from the temephos programme, retention of applied temephos, and views about temephos and mosquito control. Fieldworkers noted if temephos was present in water containers. Some 42.4% of rural and 20.7% of urban households reported no temephos programme visits within the last 12 months. Overall, 42.0% reported they had temephos placed in their water containers less than 3 months previously. Fieldworkers observed temephos in at least one container in 21.1% of households. Recent temephos application and observed temephos were both significantly more common in urban households, when other household variables were taken into account; in rural areas, smaller households were more likely to have temephos present. Most households (74.4%) did not think bathing with water containing temephos carried any health risk. Half (51%) believed drinking or cooking with such water could be harmful and 17.6% were unsure. Significantly fewer households in intervention sites (16.5%) than in control sites (26.0%) (Risk Difference - 0.095, 95% confidence interval - 0.182 to -0.009) had temephos observed in their water; more households in intervention clusters (41.8%) than in control clusters (31.6%) removed the applied temephos quickly. Although fewer households in intervention sites (82.7%) compared with control sites (86.7%) (RD -0.04, 95% CI -0.067 to -0.013) agreed temephos and fumigation was the best way to avoid mosquitoes, the proportion believing this remained very high. Coverage with the government temephos programme was low, especially in rural areas. Despite an intervention encouraging non-chemical mosquito control, most households continued to believe that chemicals are the best control method. ISRCTN: 27581154 .


Morbidity after transsternal thymectomy for myasthenia gravis: a changing perspective?
A detailed assessment of recent changes in morbidity and mortality after transsternal thymectomy for myasthenia gravis is pending. To this end, a retrospective analysis was carried out of morbidity and mortality rates in 125 patients subjected to transsternal thymectomy for myasthenia gravis in the periods 1976-85 (1st decade) and 1986-95 (2nd decade). Composition of patients did not change much over time, except for more concomitant preoperative disease in the second decade (p = 0.001). None the less, complication rates were not higher, nor did the pattern of complications alter. Mortality was nil in both decades. There was no difference over the decades as to length of ventilation, intensive care treatment, or overall hospitalization. Most complications did not reveal a monocausal relationship, suggesting that a combination of risk factors was implicated. Further reductions in future morbidity rates after transsternal thymectomy for myasthenia gravis seem unlikely as patient preoperative state is unlikely to improve. In the light of the deteriorating preoperative patient condition, constant postoperative morbidity rates indicate that patient care has in fact improved.


TRPV1 is important for mechanical and heat sensitivity in uninjured animals and development of heat hypersensitivity after muscle inflammation.
Inflammatory thermal hyperalgesia is principally mediated through transient receptor potential vanilloid 1 (TRPV1) channels, as demonstrated by prior studies using models of cutaneous inflammation. Muscle pain is significantly different from cutaneous pain, and the involvement of TRPV1 in hyperalgesia induced by muscle inflammation is unknown. We tested whether TRPV1 contributes to the development of mechanical and heat hypersensitivity of the paw in TRPV1(-/-) mice after muscle inflammation. Because TRPV1(-/-) mice lack TRPV1 at the site of inflammation (muscle) and at the testing site (paw), we do not know whether TRPV1 is important as a mediator of nociceptor sensitization in the muscle or as a heat sensor in the paw. Using recombinant herpesviruses, we reexpressed TRPV1 in TRPV1(-/-) mice in primary afferents innervating skin, muscle, or both to determine which sites were important for the behavioral deficits. Responses to repeated application of noxious mechanical stimuli to the hind paw were enhanced in TRPV1(-/-) mice; this was restored by reexpression of TRPV1 into skin. Withdrawal latencies to noxious heat were increased in TRPV1(-/-) mice; normal latencies were restored by reexpression of TRPV1 in both skin and muscle. Heat hypersensitivity induced by muscle inflammation did not develop in TRPV1(-/-) mice; mechanical hypersensitivity was similar between TRPV1(-/-) and TRPV1(+/+) mice. Heat hypersensitivity induced by muscle inflammation was restored by reexpression of TRPV1 into both muscle and skin of TRPV1(-/-) mice. These results suggest that TRPV1 serves as both a mediator of nociceptor sensitization at the site of inflammation and as a heat sensor at the paw.


Elimination of mucosal cyathostome larvae by five daily treatments with fenbendazole.
The efficacy of five daily treatments with 7.5 mg fenbendazole/kg bodyweight against mucosal cyathostome larvae was evaluated in 20 12- and 24-month-old ponies with naturally acquired cyathostome infections. After three weeks communal grazing on infected pasture and six weeks indoors, one group of 10 ponies were treated. Six weeks later, both groups of ponies were humanely destroyed and their burdens of large intestinal cyathostome worms, including luminal parasites and mucosal larvae, were assessed. In the control animals approximately 7 per cent of the total worm burden was present in the gut lumen and 93 per cent was present as larvae in the large intestinal mucosa. The efficacy of fenbendazole against the luminal cyathostomes was 90.7 per cent (P < 0.01). The total numbers of mucosal larvae, recovered after digestion, were reduced by 95.3 per cent (P < 0.0005); mucosal late third and fourth stage larvae were reduced by 99.4 per cent (P < 0.0001), and early inhibited third stage larvae by 91.5 per cent (P < 0.005).


[Diagnostic and therapeutic approach to pregnant women suspect on antiphospholipid syndrome].
Antiphospholipid syndrome includes the presence of antiphospholipid antibodies, vascular thrombosis and reproductive function disturbances. The aim was to show our diagnostic and therapeutic experiences. 62 women were included in study, 32 with primary antiphospholipd syndrome (PAPS), and 30 with secondary antiphospholipid syndrome (SAPS). 36 were pregnant and studied prospectively throughout pregnancy and six weeks after the delivery. Lupus-anticoagulant (LA) was positive in 23 patients with PAPS (71.9%), and in 10 patients with SAPS (33.3%). In SAPS group anticardiolipin antibodies (aCL) was positive in 8 patients (26.6%) compared to PAPS group with 3 aCL positive patients (9.4%). Antibeta2glycoprotein1 (antibeta2GP1) was positive in 3 patients with PAPS. Complications in previous pregnancies were in 25 cases (69.4%) spontaneous abortion, in 7 cases (19.4%) preeclampsia with intrauterine growth restriction (IUGR) in 3 patients. In 4 cases the complication was fetal death in utero. Average pregnancy lasted 37.06+/-0.707 weeks. Therapy with low dose aspirin and low-molecular-weight heparin was successful in 97.2%.


Analysis of mother-to-infant transmission of hepatitis C virus: quasispecies nature and buoyant densities of maternal virus populations.
Mother-to-infant transmission of hepatitis C virus (HCV) was analyzed by sequencing of viral RNA and semiquantitative polymerase chain reaction following ultracentrifugation of maternal sera. In two mother-infant pairs, the hypervariable region 1 (HVR1) and carboxyl terminus of envelope 1 (E1) were sequenced. Both viral sequences in the infants were less diverse than those of their mothers. Although the E1 sequences were almost identical in each mother-infant pair, the HVR1 sequences of the infants were related, but not identical, to those of the mothers. Serial examinations of one infant revealed that the HVR1 nucleotide sequence did not change from 10 days to 3 months of age. In six mothers with uninfected infants, all of the dense fractions of sera contained significant amounts of HCV RNA, whereas in six mothers with infected infants, only two of those fractions contained significant amounts of HCV RNA. These results indicate that the strains of HCV detected in the infants were not dominant in the mothers, but were still transmissible to the infants. As dense fractions are known to contain antibody-bound HCV particles, maternal antibodies against HCV may inhibit viral transmission.


Why do people perceive ingroup homogeneity on ingroup traits and outgroup homogeneity on outgroup traits?
People tend to perceive ingroup homogeneity on ingroup stereotypical traits and outgroup homogeneity on outgroup stereotypical traits (e.g., Kelly, 1989; Simon, 1992a; Simon & Pettigrew, 1990). If it is assumed that people use homogeneity ratings to indicate the extent to which groups possess traits, then this stereotype effect may be interpreted as an expression of perceived trait possession (i.e., ingroups possess ingroup stereotypical traits and outgroups possess outgroup stereotypical traits). If it is further assumed that research participants abide by the conversational norm of appropriate quantity (e.g., Bless, Strack, & Schwarz, 1993), then this stereotype effect should be significantly reduced following prior expressions of perceived trait possession. A literature review and two minimal group experiments (Ns = 75, 104) supported this prediction. This evidence is discussed in relation to the outgroup homogeneity effect and self-categorization theory.


CB1 receptor affects cortical plasticity and response to physiotherapy in multiple sclerosis.
Therapeutic effects of physical therapy in neurologic disorders mostly rely on the promotion of use-dependent synaptic plasticity in damaged neuronal circuits. Genetic differences affecting the efficiency of synaptic plasticity mechanisms could explain why some patients do not respond adequately to the treatment. It is known that physical exercise activates the endocannabinoid system and that stimulation of cannabinoid CB1 receptors (CB1Rs) promotes synaptic plasticity in both rodents and humans. We thus tested whether CB1R genetic variants affect responsiveness to exercise therapy. We evaluated the effect of a genetic variant of the CB1R associated with reduced receptor expression (patients with long AAT trinucleotide short tandem repeats in the CNR1 gene) on long-term potentiation (LTP)-like cortical plasticity induced by transcranial magnetic theta burst stimulation (TBS) of the motor cortex and, in parallel, on clinical response to exercise therapy in patients with multiple sclerosis. We found that patients with long AAT CNR1 repeats do not express TBS-induced LTP-like cortical plasticity and show poor clinical benefit after exercise therapy. Our results provide the first evidence that genetic differences within the CB1R may influence clinical responses to exercise therapy, and they strengthen the hypothesis that CB1Rs are involved in the regulation of synaptic plasticity and in the control of spasticity in humans. This information might be of great relevance for patient stratification and personalized rehabilitation treatment programs.


FLOR-ID: an interactive database of flowering-time gene networks in Arabidopsis thaliana.
Flowering is a hot topic in Plant Biology and important progress has been made in Arabidopsis thaliana toward unraveling the genetic networks involved. The increasing complexity and the explosion of literature however require development of new tools for information management and update. We therefore created an evolutive and interactive database of flowering time genes, named FLOR-ID (Flowering-Interactive Database), which is freely accessible at http://www.flor-id.org. The hand-curated database contains information on 306 genes and links to 1595 publications gathering the work of >4500 authors. Gene/protein functions and interactions within the flowering pathways were inferred from the analysis of related publications, included in the database and translated into interactive manually drawn snapshots.


[Anti TNF-α (infliximab) treatment for intravenous immunoglobulin (IVIG) resistance patients with acute Kawasaki disease the effects of anticytokine therapy].
Among the patients with acute Kawasaki disease treated with intravenous immunoglobulin (IVIG), 10-20 % demonstrate resistance or incomplete effects. Cardiac complication such as the coronary arterial aneurysm is frequent in these patients. For patients with IVIG-resistance, we have surveyed the efficacy and safety of anti-cytokine therapy with use of infliximab (Remicade), chimera type anti TNF-α agent, for children. After May, 2005, Remicade has been used in >500 pediatric patients in whom IVIG and intravenous methylprednisolone pulse therapy did not show significant effects. The efficacy and safety of Remicade on patients with IVIG-resistant Kawasaki disease has been observed but 10~20 % of patients was Remicade-resistant. Re-treatment with IVIG or steroids was also effective. The efficacy of Remicade for reducing the fever duration, CRP, WBC counts was promising, but reduction of the incidence of coronary aneurysm was not confirmed. Randomized clinical trial will be needed.


Adjuvant transarterial chemoembolization for patients after curative resection of hepatocellular carcinoma: a meta-analysis.
To evaluate the efficacy and safety of adjuvant transarterial chemoembolization (TACE) after curative hepatectomy in improving the survival of patients with primary hepatocellular carcinoma (HCC). MEDLINE, Embase and the Cochrane Library were searched for randomized or nonrandomized studies comparing postoperative adjuvant TACE with curative resection alone. Meta-analysis was performed after converting time-event data into a hazard ratio (HR), using an inverse diversity model. Eight randomized controlled trials (RCTs) and 12 retrospective studies matched the selection criteria, thereby including 3191 patients (779 in RCT, 2412 in observational studies) for the meta-analysis. The meta-analysis showed that receiving adjuvant TACE was associated with improved overall survival (OS, ln[HR] = 0.70, 95%CI: 0.63-0.78, p < .001) and recurrence-free survival (RFS, ln[HR] = 0.69, 95%CI: 0.63-0.76, p < .001) after curative hepatectomies. The results of observational studies were consistent with those of RCTs. Furthermore, meta-regression was utilized to detect study-level factors associated with treatment outcome. It revealed that overall survival was similar among patients treated with various combinations of chemotherapeutic drugs. Subgroup analyses demonstrated that repeated TACE interventions do not provide a higher survival benefit compared with a single course, and patients with a single tumor or tumor size ≥5cm might stand to benefit the most from adjuvant TACE therapy. This meta-analysis demonstrated that postoperative adjuvant TACE could achieve higher OS and RFS than surgical resection alone. However, these results need to be validated through further high-quality clinical studies.


Differential requirements for retinal degeneration slow intermolecular disulfide-linked oligomerization in rods versus cones.
It is commonly assumed that the ultrastructural organization of the rim region of outer segment (OS) discs in rods and lamellae in cones requires functional retinal degeneration slow/rod outer segment membrane protein 1 (Rds/Rom-1) complexes. Cysteine-150 (C150) in Rds has been implicated in intermolecular disulfide bonding essential for functional Rds complexes. Transgenic mice containing the Rds C150S mutation (C150S-Rds) failed to form higher-order Rds oligomers, although interactions between C150S-Rds and Rom-1 occurred in rods, but not in cones. C150S-Rds mice exhibited marked early-onset reductions in cone function and abnormal OS structure. In contrast, C150S-Rds expression in rods partly rescued the rds(+/-) phenotype. Although C150S-Rds was detected in the OSs in rods and cones, a substantial percentage of C150S-Rds and cone opsins were mislocalized to different cellular compartments in cones. The results of this study provide novel insights into the importance of C150 in Rds oligomerization and the differences in Rds requirements in rods versus cones. The apparent OS structural differences between rods and cones may cause cones to be more susceptible to the elimination of higher-order Rds/Rom-1 oligomers (e.g. as mediated by mutation of the Rds C150 residue).


Release and Reconstruction of a Postburn Deformed Breast in a Young Woman.
Burn injuries to the anterior chest wall in the young woman may cause disfiguration or lack of development of the breasts during puberty. Often the patients are referred after puberty with an apparent lack of breast development due to firm postburn scar tissue constricting the anterior chest wall. We report a case where a young female with a postburn disfiguration and apparent diminished breast development was reconstructed successfully with incision only through the restricting burn scar, a periareolar skin excision and split-thickness skin grafting of the subsequent outburst of constricted breast tissue.


Mosaicism in fragile X affected males.
Fragile X affected males have an expansion of a CGG repeat and a hypermethylated CpG island 5' to the FMR-1 gene. Mosaic males with both a premutation and full mutation have been noted among the affected individuals. Such mosaic males are most easily identified by the presence of a methylated restriction fragment characteristic of the full mutation and an additional unmethylated fragment in the premutation range in Southern analyses with EcoR I and the methylation-sensitive enzyme Eag I and a probe such as StB12.3. We analyzed a group of affected fragile X males by Southern blotting and found 41% (61/148) to be mosaic. The 148 individuals were divided between 36 pairs of brothers and 76 unrelated males. Little difference in the number of mosaics was seen between the brothers and the unrelated males nor was the expected distribution of mosaicism in brother pairs different from observed. Thus, these data do not suggest a familial basis for mosaicism. Our observation that 41% affected fragile X males were mosaic is significantly higher than previous reports. The difference is likely due to technical modifications which permitted the identification of faint premutation bands in some patients. The high percentage of affected males with mosaicism seen here suggests that the occurrence of such individuals may be a much more frequent event than presently recognized.


Practices around acute diarrheal illness diagnosis, counseling, and reporting: laboratory and health-care practitioners in North Carolina, 2004.
To describe foodborne disease surveillance in North Carolina, particularly diagnosis, counseling, and reporting of diagnoses from health-care practitioners (HCPs) and reporting of positive laboratory results from clinical diagnostic laboratories. A survey was administered on knowledge of diagnostic testing and reporting practices for foodborne disease among HCPs in western North Carolina. We also queried laboratories statewide about foodborne disease testing and reporting practices. HCPs in specialties likely to diagnose acute diarrheal illness (ADI) participated (319/1442, 22% response rate). Only 66% of HCPs were comfortable with their knowledge of foodborne illness, and 68% were comfortable diagnosing and treating foodborne illnesses. In the past 30 days, 29% of HCPs did not request a stool culture from their ADI patients. We estimate that, overall, 8% of ADI patients who sought care in this region have a diagnosis that is reported to the health department (HD). The laboratory response rate was 39% (42/108), and 70% gave timely foodborne diagnosis reports to the HD. In this cross-sectional study, causes of reporting behavior could not be explored. In addition, HCPs survey response rates were low. Many HCPs were not comfortable with their knowledge and did not adequately provide counseling on prevention of foodborne illnesses. HCPs in western North Carolina may benefit from provider training on foodborne illness counseling and reporting. Improvements in communication between laboratories, HCPs, and HDs may increase HCP confidence in diagnosing foodborne illnesses and increase counseling of patients on prevention. Increased requests for testing of stool specimens by HCPs could substantially impact foodborne disease reporting in North Carolina.


Four forms of tyrosine hydroxylase are present in human adrenal medulla.
Alternative splicing can result in up to four forms of human tyrosine hydroxylase (HTH) mRNA (mRNAHTH). In the adrenal gland, a major site of catecholamine biosynthesis, the presence of all four mRNAHTH forms is controversial. In the present study, postmortem human adrenal medullary tissue was analyzed for the presence of multiple forms of HTH protein by blot immunolabeling. Electrophoretic transfers were developed with affinity-purified rabbit anti-HTH antibodies raised against peptides that reproduced the unique amino acid sequences predicted by the four mRNAHTH forms. All four of the predicted HTH protein forms were present in the adrenal glands from a diverse sample population.


Changes in blood flow and oxygen metabolism during visual stimulation in carotid artery disease: effect of baseline perfusion and oxygen metabolism.
Severe atherosclerotic disease of the carotid arteries may affect perfusion in the posterior circulation according to the degree of collateral supply. The purpose of this study was to determine whether the responses of regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of oxygen (rCMRO2) during neural stimulation are affected by the baseline perfusion or oxygen metabolism. We used PET to measure rCBF, rCMRO2, and regional oxygen extraction fraction (rOEF) in 13 patients with carotid artery steno-occlusive lesions at baseline and during visual stimulation. We examined whether the changes in CBF, CMRO2, and OEF during visual stimulation were correlated with the baseline values of these parameters in the visual cortex. With visual stimulation, rCBF increased in all patients, whereas rCMRO2 showed variable changes. The baseline rCMRO2 value showed a positive relationship with the degree of rCBF increase and a negative relationship to the degree of rCMRO2 increase. rCMRO2 decreased in patients with relatively high baseline rCMRO2 values, resulting in dissociation of the rCMRO2 response from the rCBF response. The rCBF increase was large in the region with an increased baseline rOEF value. These variable changes in rCBF and rCMRO2 resulted in a significant correlation between the values of rCBF and rCMRO2 during visual stimulation in contrast to the lack of such a correlation at baseline. In patients with cerebrovascular disease, neural stimulation may induce variable changes in rCBF and rCMRO2 according to the baseline perfusion and oxygen metabolism.