Evaluating herbal medicine for the management of Herpes zoster in human immunodeficiency virus-infected patients in Kampala, Uganda.
This study was carried out to evaluate the potential effectiveness of herbal treatments used for herpes zoster (HZ) by a great number of people living with acquired immunodeficiency syndrome (PLWAs) in Uganda. Kampala, Uganda. Clinics of indigenous traditional healers, at the Department of Medicine of Mulago Hospital, Makerere University, and at The AIDS Support Organization (TASO) Clinic, providing primary care to people living with HIV and AIDS. DESIGN, PATIENTS, AND PARTICIPANTS: Nonrandomized, nonplacebo controlled, observational study in two phases. Inclusion criteria included HIV seropositivity and a recent HZ attack. In phase 1, 52 patients were enrolled, treated, and followed for up to 3 months at three healers' clinics, and compared to 52 TASO Clinic controls receiving ambulatory care. Phase 2 was similar in design to phase 1, but lasted longer (6-month follow-up) and involved 154 hospital outpatients treated with herbal medicine and 55 TASO controls. In both phases, healer patients were given herbal treatment according to healers' prescriptions, while controls received either symptomatic treatment or acyclovir. Healer patients and controls experienced similar rates of resolution of their HZ attacks. Fewer healer patients than controls experienced superinfection in phase 1 (18% versus 42%, p < 0.02) and fewer healer patients showed keloid formation in either phase. This difference was not statistically significant. In both phases, zoster-associated pain resolved substantially faster among healer patients with a higher degree of significance in phase 2 where the progression of pain over time could be seen because of the longer follow-up (phase 1: maximum p value (pmax) < pmax < 0.02 at 1 month, pmax < 0.005 at 2 months, pmax < 0.0001 at 3 months). Herbal treatment is an important local and affordable primary care alternative for the management of HZ in HIV-infected patients in Uganda and similar settings.


Detecting stable adsorbates of (1S)-camphor on Cu(111) with Bayesian optimization.
Identifying the atomic structure of organic-inorganic interfaces is challenging with current research tools. Interpreting the structure of complex molecular adsorbates from microscopy images can be difficult, and using atomistic simulations to find the most stable structures is limited to partial exploration of the potential energy surface due to the high-dimensional phase space. In this study, we present the recently developed Bayesian Optimization Structure Search (BOSS) method as an efficient solution for identifying the structure of non-planar adsorbates. We apply BOSS with density-functional theory simulations to detect the stable adsorbate structures of (1S)-camphor on the Cu(111) surface. We identify the optimal structure among eight unique types of stable adsorbates, in which camphor chemisorbs via oxygen (global minimum) or physisorbs via hydrocarbons to the Cu(111) surface. This study demonstrates that new cross-disciplinary tools, such as BOSS, facilitate the description of complex surface structures and their properties, and ultimately allow us to tune the functionality of advanced materials.


[A clinical study on composite transplantation of meshed split-thickness autograft and heterologous dermal matrix].
To investigate the feasibility of the composite transplantation of 1:3 meshed split-thickness autograft and acellular heterologous (porcine) dermal matrix. 9 inpatients with full thickness skin burn or hypertrophic scar were selected in this study. After the eschar or scar was excised, the wound was covered with acellular heterologous dermal matrix. Then the meshed (1:3) split-thickness autologous skin sheet was grafted on the dermal matrix. Before dressing up, the radiated pigskin was placed on the composite transplants. The composite transplantation was successfully used in 9 cases. The meshed split-thickness autograft was expanded 3 times and covered the dermal matrix tightly. The clinical results of the composite transplantation were similar to that of intermediate split thickness skin graft or full thickness skin graft. The composite transplantation of meshed (1:3) split-thickness autograft and acellular heterologous (porcine) dermal matrix allowed the expansion of the autologous skin sheet to 3 times. The clinical results were similar to that of intermediate split thickness skin graft or full thickness skin graft.


Quality assessment and assurance in clinical hyperthermia: requirements and procedures.
The ultimate goal of quality assessment and quality assurance in clinical hyperthermia must be the delivery of satisfactorily similar thermotherapy to all patients entered into a given treatment protocol. Therefore, in addition to dealing with performance evaluation and calibration of equipment for heating and thermometry, hyperthermia quality assurance must also address specification, planning, administration, documentation, evaluation, and reconstruction of the clinical treatments themselves.


Biogeochemical and molecular signatures of anaerobic methane oxidation in a marine sediment.
Anaerobic methane oxidation was investigated in 6-m-long cores of marine sediment from Aarhus Bay, Denmark. Measured concentration profiles for methane and sulfate, as well as in situ rates determined with isotope tracers, indicated that there was a narrow zone of anaerobic methane oxidation about 150 cm below the sediment surface. Methane could account for 52% of the electron donor requirement for the peak sulfate reduction rate detected in the sulfate-methane transition zone. Molecular signatures of organisms present in the transition zone were detected by using selective PCR primers for sulfate-reducing bacteria and for Archaea. One primer pair amplified the dissimilatory sulfite reductase (DSR) gene of sulfate-reducing bacteria, whereas another primer (ANME) was designed to amplify archaeal sequences found in a recent study of sediments from the Eel River Basin, as these bacteria have been suggested to be anaerobic methane oxidizers (K. U. Hinrichs, J. M. Hayes, S. P. Sylva, P. G. Brewer, and E. F. DeLong, Nature 398:802-805, 1999). Amplification with the primer pairs produced more amplificate of both target genes with samples from the sulfate-methane transition zone than with samples from the surrounding sediment. Phylogenetic analysis of the DSR gene sequences retrieved from the transition zone revealed that they all belonged to a novel deeply branching lineage of diverse DSR gene sequences not related to any previously described DSR gene sequence. In contrast, DSR gene sequences found in the top sediment were related to environmental sequences from other estuarine sediments and to sequences of members of the genera Desulfonema, Desulfococcus, and Desulfosarcina. Phylogenetic analysis of 16S rRNA sequences obtained with the primers targeting the archaeal group of possible anaerobic methane oxidizers revealed two clusters of ANME sequences, both of which were affiliated with sequences from the Eel River Basin.


Laparoscopic versus open colectomy for locally advanced T4 colonic cancer: meta-analysis of clinical and oncological outcomes.
The aim of this study was to review the early postoperative and oncological outcomes after laparoscopic colectomy for T4 cancer compared with open surgery. MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched for any relevant clinical study comparing laparoscopic and open colectomy as treatment for T4 colonic cancer. The risk ratio (RR) with 95 per cent c.i. was calculated for dichotomous variables, and the mean difference (m.d.) with 95 per cent confidence interval for continuous variables. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was implemented for assessing quality of evidence (QoE). Twenty-four observational studies (21 retrospective and 3 prospective cohort studies) were included, analysing a total of 18 123 patients: 9024 received laparoscopic colectomy and 9099 underwent open surgery. Laparoscopic colectomy was associated with lower rates of mortality (RR 0.48, 95 per cent c.i. 0.41 to 0.56; P < 0.001; I2 = 0 per cent, fixed-effect model; QoE moderate) and complications (RR 0.61, 0.49 to 0.76; P < 0.001; I2 = 20 per cent, random-effects model; QoE very low) compared with an open procedure. No differences in R0 resection rate (RR 1.01, 1.00 to 1.03; P = 0.12; I2 = 37 per cent, random-effects model; QoE very low) and recurrence rate (RR 0.98, 0.84 to 1.14; P = 0.81; I2 = 0 per cent, fixed-effect model; QoE very low) were found. Laparoscopic colectomy for T4 colonic cancer is safe, and is associated with better clinical outcomes than open surgery and similar oncological outcomes.


Meckel's diverticulum manifested by a subcutaneous abscess.
This case report describes an extremely rare complication of a Meckel's diverticulum: enterocutaneous fistula of the diverticulum. The presence of Meckel's diverticulum is a well known entity, but subcutaneous perforation of the diverticulum is very rare. Here we report the case of a patient with the complaint of a right lower quadrant abscess, preoperatively diagnosed as enterocutaneous fistula, which was determined intraoperatively to be a fistula resulting from Meckel's diverticulum.


[Chronic periaortitis].
Chronic periaortitis is a rare fibroinflammatory disorder which affects the abdominal aorta and may spread into the retroperitoneum, often encasing the ureters. An aneurysma of the abdominal aorta and vasculitis of the thoracic aorta and of supra-aortic vessels may also coexist. Chronic periaortitis can be idiopathic or secondary to different triggers such as drugs, tumors and infections. Abdominal and/or low back pain is the hallmark symptom. Laboratory markers of inflammation are usually increased. The diagnosis rests on computerized tomography or magnetic resonance imaging, which typically show a retroperitoneal mass displacing the aorta anteriorly and the ureters medially. Positron-emission tomography may assist in defining disease activity and extension. Chronic periaortitis should be differentiated from other fibrosing disorders of various origins. Histology is required in atypical cases to secure the diagnosis. Treatment is based on high-dose steroids with a tapering scheme combined with immunosuppressive agents in refractory or relapsing disease. In case of ureter obstruction early DJ-catheter placement is required. Operative interventions to relieve ureter obstruction are rarely necessary provided immunosuppressive treatment is timely instituted.


Characterization of anionic amino acid transport systems in mouse mammary gland.
L-glutamate was transported into mammary tissue via Na(+)-dependent system XAG- that strongly interacted with both D- and L-isomers of aspartate but only with L-isomer of glutamate. Replacement of Cl- by gluconate from the extracellular medium did not affect the uptake of L-glutamate. Although neutral amino acids weakly inhibited the uptake of L-glutamate, there was no evidence for the heterogeneity of anionic amino acid transport system. The XAG- system was inhibited by sulfhydryl group blocking reagent N-ethylmalemide. Low pH (6) partially inhibited the uptake by L-glutamate by mammary tissue. Prior loading of mammary tissue with L-glutamate slightly down regulated its uptake. Culturing pregnant mouse mammary tissue explants in vitro in the presence of lactogenic hormones (insulin plus cortisol plus prolactin) did not affect appreciably the uptake of L-glutamate.


A case of penetrating neck trauma in a child.
Penetrating injuries to the neck are potentially devastating, and recommendations concerning their evaluation have generated extensive discussion over the years. In this article, we present the case of a 9-year-old girl who narrowly missed a serious vascular injury when she fell on a pencil. We also discuss the most current recommendations concerning management of zone II injuries to the neck of a pediatric patient.


Metabolic and genomic diversity of rhizobia isolated from field standing native and exotic woody legumes in southern Ethiopia.
Eighty-seven rhizobial strains isolated from root nodules of field standing native and exotic woody legumes in southern Ethiopia were characterized using the Biolog method and AFLP fingerprinting technique. Cluster analysis of the metabolic and genomic fingerprints revealed 18 and 25 groups, respectively, demonstrating considerable diversity in rhizobial population indigenous to Ethiopian soils. While 25 strains (29%) were linked to members of Agrobacterium, Bradyrhizobium, Mesorhizobium, Rhizobium or Sinorhizobium, the bulk of the strains formed several distinct groups in both methods and did not relate to reference species included in the study. In contrast to exotic species which formed symbiosis with strains of only one specific genomic group, indigenous host species nodulated by metabolically and genomically diverse groups. The results in this study support the view, that long-term association between the symbionts allows gradual differentiation and diversity in compatible rhizobial population resident in native soils. Lack of significant metabolic and genomic relatedness to the reference strains in our results suggested that test strains in our collection probably included 'unique' types, which belong to several yet undefined rhizobial species.


Hypersonic Poration: A New Versatile Cell Poration Method to Enhance Cellular Uptake Using a Piezoelectric Nano-Electromechanical Device.
Efficient delivery of genes and therapeutic agents to the interior of the cell is critical for modern biotechnology. Herein, a new type of chemical-free cell poration method-hypersonic poration-is developed to improve the cellular uptake, especially the nucleus uptake. The hypersound (≈GHz) is generated by a designed piezoelectric nano-electromechanical resonator, which directly induces normal/shear stress and "molecular bombardment" effects on the bilayer membranes, and creates reversible temporal nanopores improving the membrane permeability. Both theory analysis and cellular uptake experiments of exogenous compounds prove the high delivery efficiency of hypersonic poration. Since target molecules in cells are accumulated with the treatment, the delivered amount can be controlled by tuning the treatment time. Furthermore, owing to the intrinsic miniature of the resonator, localized drug delivery at a confined spatial location and tunable arrays of the resonators that are compatible with multiwell plate can be achieved. The hypersonic poration method shows great delivery efficacy combined with advantage of scalability, tunable throughput, and simplification in operation and provides a potentially powerful strategy in the field of molecule delivery, cell transfection, and gene therapy.


Predicting the postmortem submersion interval for human remains recovered from U.K. waterways.
This article aims to increase accuracy in estimating the postmortem submersion interval (PMSI) for bodies recovered from rivers in the United Kingdom. Data were collected from closed case files, crime scene reports, and autopsy files concerning bodies recovered over a 15-year period from the River Clyde, Scotland, and the River Mersey and canals in northwest England. One hundred and eighty-seven cases met the study criteria and were scored by quantifying the overall amount of decomposition observed in each case. Statistical analysis showed that the duration of a body's submergence in water and the temperatures to which it was exposed, as measured in accumulated degree days (ADD), had a significant effect on the decay process. Further analysis indicated that there were no significant differences in decomposition between the waterways. By combining the data from all study samples, it was possible to produce a single linear regression model for predicting ADD from observed decomposition.


Use of recombinant Epstein-Barr virus early antigen for detection of antibody in patients with nasopharyngeal carcinoma.
Nasopharyngeal carcinoma (NPC) is one of the most common cancers in southern China and Taiwan. Serological studies revealed the close-relationship between NPC and Epstein-Barr virus (EBV). Elevated serum and saliva levels of anti-EBV antibodies are detected in patients with NPC. Therefore, Development Center for Biotechnology prepared the EBV-early antigen (EA-D) by recombinant DNA technique for screening the serum and throat washing samples from patients with head and neck cancers. The BMRF1 gene for EBV early antigen (EA-D) was placed into the plasmid pDB18, then transformed into an Escherichia coli strain containing the lambda cI857 temperature-sensitive repressor. Heat treatment of the transformant, at exponential growth phase, inactivated the cI protein and induced an over-expression of the EA-D protein. Next, the EA-D was purified by chromatography and characterized as a protein of molecular weight 47 kDa, by sodium dodecyl sulfate-polyacry lamide gel electrophoresis (SDS-PAGE) and Western blot analysis using monoclonal anti-EA antibody and sera from patients with nasopharyngeal carcinoma (NPC). Enzyme-linked immunosorbent assay (ELISA) with the purified EA-D antigen was used to screen 129 serum and throat washing (TW) samples from patients with head and neck tumors, 24 from patients with a nonmalignant disease and 44 from normal donors. Experimental results indicated significantly higher positive rates of EA-D IgA (69%) and EA-D IgG (91%) in NPC sera than in the sera of patients with other head and neck tumors and normal controls. TW samples from patients with NPC also showed a higher positive rate (34%) than the other groups (7-20%). Results in this study demonstrate that the bacterially expressed EA-D antigen could be recognized by sera from patients with NPC and monoclonal anti-EA antibody. Thus, it has potential use in ELISA for screening EBV-related diseases such as NPC.


Achieving 20% External Quantum Efficiency for Fully Solution-Processed Organic Light-Emitting Diodes Based on Thermally Activated Delayed Fluorescence Dendrimers with Flexible Chains.
Actualizing high-efficiency thermally activated delayed fluorescent (TADF) organic light-emitting diodes (OLEDs) with fully wet processes is of great significance to the development of purely organic electroluminescence and the application of large-area OLED displays. Herein, new strategies are proposed to develop the TADF dendrimers with tunable colors by adjusting the way of linking branches to the core and the numbers of peripheral branches. Due to an energy gradient and efficient exciton utilization in the core-dendron system, the solution-processed OLEDs with the four dendrimers 5CzBN-O-Cz, 5CzBN-O-2Cz, 5CzBN-Cz, and 5CzBN-2Cz all give rise to low turn-on voltages and great device efficiency. Notably, 5CzBN-2Cz affords record-high fully solution-processed TADF OLEDs with external quantum efficiency of above 20%, which is significantly comparable to the efficiency of TADF OLEDs based on vacuum deposition. The work offers a guideline for designing solution-processable materials, paving the way toward practical applications of large-area fully solution-processed OLEDs.


Horizontal transfer of a plant transposon.
The majority of well-documented cases of horizontal transfer between higher eukaryotes involve the movement of transposable elements between animals. Surprisingly, although plant genomes often contain vast numbers of these mobile genetic elements, no evidence of horizontal transfer of a nuclear-encoded transposon between plant species has been detected to date. The most mutagenic known plant transposable element system is the Mutator system in maize. Mu-like elements (MULEs) are widespread among plants, and previous analysis has suggested that the distribution of various subgroups of MULEs is patchy, consistent with horizontal transfer. We have sequenced portions of MULE transposons from a number of species of the genus Setaria and compared them to each other and to publicly available databases. A subset of these elements is remarkably similar to a small family of MULEs in rice. A comparison of noncoding and synonymous sequences revealed that the observed similarity is not due to selection at the amino acid level. Given the amount of time separating Setaria and rice, the degree of similarity between these elements excludes the possibility of simple vertical transmission of this class of MULEs. This is the first well-documented example of horizontal transfer of any nuclear-encoded genes between higher plants.


Magnetic resonance imaging evaluation of cardiac masses.
Cardiac tumors are extremely rare; however, when there is clinical suspicion, proper diagnostic evaluation is necessary to plan the most appropriate treatment. In this context, cardiovascular magnetic resonance imaging (CMRI) plays an important role, allowing a comprehensive characterization of such lesions. To review cases referred to a CMRI Department for investigation of cardiac and paracardiac masses. To describe the positive case series with a brief review of the literature for each type of lesion and the role of cardiovascular magnetic resonance imaging in evaluation. Between August 2008 and December 2011, all cases referred for CMRI with suspicion of tumor involving the heart were reviewed. Cases with positive histopathological diagnosis, clinical evolution or therapeutic response compatible with the clinical suspicion and imaging findings were selected. Among the 13 cases included in our study, eight (62%) had histopathological confirmation. We describe five benign tumors (myxomas, rhabdomyoma and fibromas), five malignancies (sarcoma, lymphoma, Richter syndrome involving the heart and metastatic disease) and three non-neoplastic lesions (pericardial cyst, intracardiac thrombus and infectious vegetation). CMRI plays an important role in the evaluation of cardiac masses of non-neoplastic and neoplastic origin, contributing to a more accurate diagnosis in a noninvasive manner and assisting in treatment planning, allowing safe clinical follow-up with good reproducibility.


[Expression of connective tissue growth factor in pulmonary artery at the early-stage of pulmonary fibrosis].
To ascertain whether connective tissue growth factor (CTGF) participates in the remodeling of pulmonary artery at the early-stage of bleomycin (BLM)-induced pulmonary fibrosis, mean pulmonary arterial pressure, the expression of type I and type III collagens, and the expression and location of CTGF in pulmonary artery and arteriole were investigated in the present study. Sprague-Dawley rats received instillation of BLM [5 mg/kg body weight, in 0.5 mL of normal saline (NS)] or instillation of the same amount of NS as control. Mean pulmonary arterial pressure was detected via a catheter in the pulmonary artery. Type I and type III collagens were examined with Sirius red staining under polarized light. CTGF expression was investigated by using immunohistochemistry, and was represented as average optical density and percentage of positive area of CTGF. The mean pulmonary arterial pressure was higher in rats on day 14 after BLM instillation [(19.5+/-2.9) mmHg] than that in the control rats [(14.8+/-1.2) mmHg] (P<0.05). The type I and type III collagens were increased both in pulmonary artery and arteriole of rats on day 14 after BLM instillation, compared with those in the control rats (P<0.05, P<0.01, respectively). The ratio of type I/III collagens in pulmonary artery was also higher in BLM-treated rats than that in the control rats (P<0.05). The values of average optical density of positive CTGF staining were increased both in pulmonary artery (0.37+/-0.02) and arteriole (0.40+/-0.03) of rats on day 14 after BLM instillation, compared with those in the control rats (artery, 0.34+/-0.01; arteriole, 0.29+/-0.01) (both P<0.05). The percentages of positive area of CTGF were higher in pulmonary artery (8.40+/-1.13) and arteriole (12.4+/-2.0) of rats on day 14 after BLM instillation than those in the control rats (artery: 1.42+/-0.63; arteriole: 1.16+/-0.34), respectively (both P<0.05). The increased positive CTGF staining areas were mainly located in the endothelium and smooth muscle layer. It is therefore concluded that CTGF expression increases in the endothelium and smooth muscle layer of pulmonary artery and arterioles during high pulmonary arterial pressure and remodeling of pulmonary artery at the early-stage of BLM-induced pulmonary fibrosis, and that the increased CTGF might be one of the mechanisms of maintenance and development of pulmonary hypertension.


Identification of the cpdA gene encoding cyclic 3',5'-adenosine monophosphate phosphodiesterase in Escherichia coli.
We have identified a gene, cpdA, located at 66.2 min of the chromosome of Escherichia coli that encodes cyclic 3',5'-adenosine monophosphate phosphodiesterase (cAMP phosphodiesterase, EC). The expression of beta-galactosidase, which is a product of the lacZ gene, was repressed in cells that harbored multiple copies of the plasmid carrying the cpdA gene. Northern blotting showed that the transcription of the lacZ gene was inhibited in these cells. Multiple copies of the cpdA gene decreased the intracellular concentration of cAMP, which is a positive regulator for transcription of the lacZ gene. We found that the purified CpdA protein repressed in vitro transcription from the lacP1 promoter by decreasing cAMP. In addition, we showed that the CpdA protein hydrolyzed cAMP to 5'-adenosine monophosphate and that its activity was activated by iron. Our results suggested that regulation of intracellular concentration of cAMP is dependent not only on synthesis of cAMP but also on hydrolysis of cAMP by cAMP phosphodiesterase.


Cooperation between microtubule- and actin-based motor proteins.
Organelle transport has been proposed to proceed in two steps: long-range transport along microtubules and local delivery via actin filaments. This model is supported by recent studies of pigment transport in several cell types and transport in neurons, and in several cases, class V myosin has been implicated as the actin-based motor. Mutations in mice (dilute) and yeast (myo2) have also implicated this class of myosin in organelle transport, and genetic interactions in yeast have indicated that a kinesin-related protein (Smy1p) plays a supporting role. This link between members of two different motor superfamilies has now taken a surprising turn: There is evidence for a physical interaction between class V myosins and kinesin or Smy1p in both mice and yeast.


Naloxone potentiation of effects of cholecystokinin and lithium chloride on oxytocin secretion, gastric motility and feeding.
Neurohypophyseal secretion of oxytocin (OT) in response to dehydration, hypovolemia, restraint, and parturition in rats is known to be potentiated by the opioid antagonist naloxone. The present studies demonstrated that stimulation of OT secretion by systemic injections of cholecystokinin (CCK) and lithium chloride (LiCl) likewise are potentiated by naloxone pretreatment. Moreover, the inhibitory effects of CCK and LiCl on gastric motility and feeding similarly were enhanced by naloxone. Because neurohypophyseal hormone secretion and inhibition of gastric motility are known to be mediated by oxytocinergic neurons projecting from the paraventricular nucleus of the hypothalamus, this parallel potentiation by naloxone of CCK- and LiCl-induced effects on OT secretion, gastric motility, and food intake suggests that one of the pathways involved in the central control of feeding behavior also may be oxytocinergic. These findings therefore provide evidence in support of an important role of endogenous opioid peptides in regulating OT secretion in a diffuse neuronal system that mediates an integrated neuroendocrine, autonomic, and behavioral response to CCK, LiCl, and perhaps other treatments that similarly affect ingestive behavior in rats.


Pharmacological exploitation of an off-target antibacterial effect of the cyclooxygenase-2 inhibitor celecoxib against Francisella tularensis.
Francisella tularensis, a bacterium which causes tularemia in humans, is classified as a CDC category A bioterrorism agent. In this study, we demonstrate that celecoxib, an anti-inflammatory cyclooxygenase-2 inhibitor in clinical use, exhibits activity against a type A strain of F. tularensis (Schu S4), the live vaccine strain of F. tularensis (a type B strain), and F. novicida ("F. tularensis subsp. novicida") directly in growth medium. This bacterial killing, however, was not noted with rofecoxib, despite its higher potency than that of celecoxib in inhibiting cyclooxygenase-2. The unique ability of celecoxib to inhibit the proliferation of F. tularensis could be pharmacologically exploited to develop novel anti-Francisella therapeutic agents, of which the proof of principle is demonstrated by compound 20, a celecoxib derivative identified through the screening of a celecoxib-based focused compound library. Compound 20 inhibited the intracellular proliferation of Francisella in macrophages without causing appreciable toxicity to these host cells. Together, these data support the translational potential of compound 20 for the further development of novel, potent anti-Francisella agents.


RE1-silencing Transcription Factor (REST) Is Required for Nuclear Reprogramming by Inhibiting Transforming Growth Factor β Signaling Pathway.
Differentiated cells can be reprogrammed by transcription factors, and these factors that are responsible for successful reprogramming need to be further identified. Here, we show that the neuronal repressor RE1-silencing transcription factor (REST) is rich in porcine oocytes and requires for nuclear transfer (NT)-mediated reprogramming through inhibiting TGFβ signaling pathway. REST was dramatically degraded after oocyte activation, but the residual REST was incorporated into the transferred donor nuclei during reprogramming in NT embryos. Inhibition of REST function in oocytes compromised the development of NT embryos but not that of IVF and PA embryos. Bioinformation analysis of putative targets of REST indicated that REST might function on reprogramming in NT embryos by inhibiting TGFβ pathway. Further results showed that the developmental failure of REST-inhibited NT embryos could be rescued by treatment of SB431542, an inhibitor of TGFβ pathway. Thus, REST is a newly discovered transcription factor that is required for NT-mediated nuclear reprogramming.


Intramolecular Hydroalkoxylation of Unactivated Alkenes Using Silane-Iodine Catalytic System.
A novel catalytic system using I2 and PhSiH3 for the intramolecular hydroalkoxylation of unactivated alkenes is described. NMR study indicated that in situ generated PhSiH2I is a possible active catalytic species. This catalytic system allows an efficient intramolecular hydroalkoxylation of phenyl-, trialkyl-, and 1,1-dialkyl-substituted alkenes as well as a variety of unactivated monoalkyl- and 1,2-dialkyl-substituted alkenes at room temperature. Mechanistic consideration based on significant experimental observations is also discussed.


[Identification of Host Factors Interacting with the Movement Protein of Apple Chlorotic Leaf Spot Virus by Yeast Two-Hybrid System].
In order to identify host factors which interact with the movement protein (MP) of Apple chlorotic leaf spot virus (ACLSV), ACLSV MP was cloned into the bait vector pGBKT7 and used to screen a cDNA library of Malus sylvestris cv. R12740-7A, which had previously been constructed by yeast two-hybrid sequencing transformation. The protein functions of the identified host factors were determined according to their gene annotations in GenBank. The result showed that the bait plasmid pGBKT7-MP showed no virulence or self-activating effect on yeast strain Y2H Gold. Sixty-nine interactor proteins were identified, which were divided into the following 10 classes according to their described functions: hydrolases; pathogenesis-related proteins; DNA binding proteins; phosphatases; ligases; proteins with catalytic activity; phenylalanine ammonialyases; peroxidases; NAD binding proteins; and proteins of unknown function. Bioinformatic analysis of gene homology suggested that phosphatases, pathogenesis-related proteins and glyceraldehyde-3-phosphate dehydrogenase A may play an important role in the interaction between virus and host. This study may provide a theoretical basis for the further study of viral pathogenesis and virus-host interaction mechanisms.


The zebrafish orthologue of the dyslexia candidate gene DYX1C1 is essential for cilia growth and function.
DYX1C1, a susceptibility gene for dyslexia, encodes a tetratricopeptide repeat domain containing protein that has been implicated in neuronal migration in rodent models. The developmental role of this gene remains unexplored. To understand the biological function(s) of zebrafish dyx1c1 during embryonic development, we cloned the zebrafish dyx1c1 and used morpholino-based knockdown strategy. Quantitative real-time PCR analysis revealed the presence of dyx1c1 transcripts in embryos, early larval stages and in a wide range of adult tissues. Using mRNA in situ hybridization, we show here that dyx1c1 is expressed in many ciliated tissues in zebrafish. Inhibition of dyx1c1 produced pleiotropic phenotypes characteristically associated with cilia defects such as body curvature, hydrocephalus, situs inversus and kidney cysts. We also demonstrate that in dyx1c1 morphants, cilia length is reduced in several organs including Kupffer's vesicle, pronephros, spinal canal and olfactory placode. Furthermore, electron microscopic analysis of cilia in dyx1c1 morphants revealed loss of both outer (ODA) and inner dynein arms (IDA) that have been shown to be required for cilia motility. Considering all these results, we propose an essential role for dyx1c1 in cilia growth and function.


Media, Trust in Government, and Risk Perception of COVID-19 in the Early Stage of Epidemic: An Analysis Based on Moderating Effect.
Previous research has revealed that environmental, social, and cultural factors affect people's risk perception of COVID-19, especially the influence of media and trust, while the dynamics of how they affect it is still not clear. Through the analysis of online survey data, this article shows that there are two opposed paths of action. Trust in the government will enhance people's confidence in controlling COVID-19. It then moderates and decreases the effects of people's level and frequency of concernon the risk perception (both cognition and worries) of COVID-19, on the contrary, obtaining information from unofficial channels also moderates and increases the effects of the people's level and frequency of concern on the second dimension (worries) of risk perception of COVID-19 rather than the first dimension (cognition). These conclusions have important policy implications for the control of the COVID-19 epidemic all over the world.


Tooth cracks detection and gingival sulcus depth measurement using optical coherence tomography.
The aims of this study were to develop an automatic detection technique for tooth cracks and to suggest quantitative methods for measuring gingival sulcus depth using swept-source optical coherence tomography (SS-OCT). We evaluated SS-OCT with wavelength centered at 1310 nm over a spectral bandwidth of 100 nm at a rate of 50 kHz as a new diagnostic tool for the detection of tooth cracks and gingival sulcus depth. The reliability of the SS-OCT images was verified by imaging the crack in extracted human teeth and gingival sulcus of porcine sample. The SS-OCT could automatically detect the position of various cracks and visualize the deep periodontal pockets. Therefore, the detection capability of SS-OCT images could be useful diagnostic tool for dental cracks and periodontal pockets.


Malignant phaeochromocytoma with high circulating DOPA, and clonidine-suppressible noradrenaline.
Phaeochromocytoma, "perhaps the most fascinating of all tumors" [1], can present with a broad range of clinical manifestations [2]. Once suspected, the biochemical diagnosis is straightforward in most patients since plasma and urinary levels of noradrenaline and/or adrenaline, and urinary metabolites are well above those encountered in healthy subjects or patients with essential hypertension [3,4]. Exceptions to this general rule are well known, however, hence suppression tests have found favour, particularly in cases where catecholamine levels are within, or close to, the normal range [5-7]. We present a unique patient with malignant phaeochromocytoma whose plasma noradrenaline levels were in the high-normal range, and suppressed normally with clonidine administration. He had extremely high circulating levels of dihydroxyphenylalanine (dopa) which were not affected by clonidine, and different patterns of catecholamine concentrations in tumour tissue and plasma.


[Difficulties in differential diagnosis of sagittal synostosis (scaphocephaly)].
Craniosynostosis is characterized by congenital absence or premature closure of skull sutures. The most common form of craniosynostosis is synostosis of sagittal suture followed by scaphocephaly. There are some head deformities similar to scaphocephaly such as positional and constitutional dolichocephaly, etc. These patients have no sagittal suture synostosis. However, there are difficulties in differential diagnosis between these deformities and scaphocephaly. To develop differential diagnostic criteria between dolichocephalic head deformities and true scaphocephaly following sagittal synostosis. The study included 33 patients with dolichocephaly (25 (75.8%) boys and 8 (24.2%) girls) between December 2013 and August 2022. The inclusion criterion was available CT or ultrasound data confirming or excluding sagittal synostosis. Age of patients was 8.62±7.71 (1.77-36) months. We analyzed anamnestic, clinical and radiological data. Radiological data was compared with diagnostic findings in 20 patients with scaphocephaly. Both groups were comparable in age, gender and cranial index. We present clinical and radiological signs, as well as algorithm for differential diagnosis between scaphocephaly and dolichocephaly. There are objective difficulties in differential diagnosis between scaphocephaly following sagittal synostosis and dolichocephalic head deformities. In most cases, we cannot establish the cause of congenital forms of dolichocephaly. The most likely causes may be pre- and postnatal compressive and positional effects. Ultrasound of skull sutures is preferable for differential diagnosis between these abnormalities. Correction of dolichocephaly can be carried out according to aesthetic indications with individual cranial orthoses.


Spatiotemporal expression profile of embryonic and adult ankyrin repeat and EF-hand domain containing protein 1-encoding genes ankef1a and ankef1b in zebrafish.
Recent human next-generation sequencing (NGS) studies indicate a correlation between ANKEF1 (ankyrin repeat and EF-hand domain containing protein 1) expression and cilia formation or function. Additionally, a single study conducted in the African clawed frog (Xenopus laevis) showed ankef1 is down-regulated after pharmacological fibroblast growth factor (FGF) inhibition and plays a role in protocadherin-mediated cell protrusion and adhesion. That study also revealed a critical role for ankef1 in the embryonic development of the frog, with morphants exhibiting phenotypes including spina bifida and a shortened body axis. Interestingly, while little is known about ANKEF1 function in other vertebrate systems, recent proteomic data has shown ANKEF1 enriched in ciliated cells. Likewise, publicly available EST profile databases imply ANKEF1 expression in multiple human tissues, including high levels in the testes. Together, these previous studies suggest an important role for ANKEF1 in ciliated tissues and during embryonic development. Here, we report cloning of zebrafish (Danio rerio) ankef1a, as well as its paralog, ankef1b, and expression analyses by whole-mount in situ hybridization (WISH) and quantitative polymerase chain reaction (qPCR) during embryonic development and in adult tissues. WISH shows both forms are ubiquitously expressed early in development, with more discrete expression of both transcripts in embryonic tissues known to precede or possess motile cilia, including dorsal forerunner cells (DFC) and the otic vesicles, respectively. Additionally, both transcripts are enriched in the developing pharynx and swim bladder. Our qPCR results indicate enhanced expression in the testes, along with increased expression in brain. Certainly, our experiments in the zebrafish model system with ankef1a and ankef1b provide a solid foundation for future studies to uncover the molecular pathways through which Ankef1 acts in both healthy and disease states.


Influence of Aqueous Arginine Solution on Regulating Conformational Stability and Hydration Properties of the Secondary Structural Segments of a Protein at Elevated Temperatures: A Molecular Dynamics Study.
The effects of aqueous arginine solution on the conformational stability of the secondary structural segments of a globular protein, ubiquitin, and the structure and dynamics of the surrounding water and arginine were examined by performing atomistic molecular dynamics (MD) simulations. Attempts have been made to identify the osmolytic efficacy of arginine solution, and its influence in guiding the hydration properties of the protein at an elevated temperature of 450 K. The similar properties of the protein in pure water at elevated temperatures were computed and compared. Replica exchange MD simulation was performed to explore the arginine solution's sensitivity in stabilizing the protein conformations for a wide range of temperatures (300-450 K). It was observed that although all the helices and strands of the protein undergo unfolding at elevated temperature in pure water, they exhibited native-like conformational dynamics in the presence of arginine at both ambient and elevated temperatures. We find that the higher free energy barrier between the folded native and unfolded states of the protein primarily arises from the structural transformation of α-helix, relative to the strands. Our study revealed that the water structure around the secondary segments depends on the nature of amino acid compositions of the helices and strands. The reorientation of water dipoles around the helices and strands was found hindered due to the presence of arginine in the solution; such hindrance reduces the possibility of exchange of hydrogen bonds that formed between the secondary segments of protein and water (PW), and as a result, PW hydrogen bonds take longer time to relax than in pure water. On the other hand, the origin of slow relaxation of protein-arginine (PA) hydrogen bonds was identified to be due to the presence of different types of protein-bound arginine molecules, where arginine interacts with the secondary structural segments of the protein through multiple/bifurcated hydrogen bonds. These protein-bound arginine formed different kinds of bridged PA hydrogen bonds between amino acid residues of the same secondary segments or among multiple bonds and helped protein to conserve its native folded form firmly.


Hydraulic Extrusion of the Spinal Cord and Isolation of Dorsal Root Ganglia in Rodents.
Traditionally, the spinal cord is isolated by laminectomy, i.e. by breaking open the spinal vertebrae one at a time. This is both time consuming and may result in damage to the spinal cord caused by the dissection process. Here, we show how the spinal cord can be extruded using hydraulic pressure. Handling time is significantly reduced to only a few minutes, likely decreasing protein damage. The low risk of damage to the spinal cord tissue improves subsequent immunohistochemical analysis. By performing hydraulic spinal cord extrusion instead of traditional laminectomy, the rodents can further be used for DRG isolation, thereby lowering the number of animals and allowing analysis across tissues from the same rodent. We demonstrate a consistent method to identify and isolate the DRGs according to their localization relative to the costae. It is, however, important to adjust this method to the particular animal used, as the number of spinal cord segments, both thoracic and lumbar, may vary according to animal type and strain. In addition, we illustrate further processing examples of the isolated tissues.


Accurate measurement of domain wall velocity in amorphous microwires, submicron wires, and nanowires.
A new method for measuring the domain wall velocity in a single, ultrathin ferromagnetic amorphous wire with the diameter down to 100 nm is presented. The method has been developed in order to increase the sensitivity in studying the domain wall propagation in bistable magnetic wires in a wide range of field amplitudes, with much larger values of the applied field as compared to those employed when studying the wall propagation in typical amorphous microwires. The large fields required to propagate the domain walls in ultrathin wires are able to nucleate new domain walls in the samples and, therefore, they can affect the accuracy of the entire measurement. The proposed experimental setup prevents such situations by using a number of complex pick-up coils, which allow the detection of the direction of the wall propagation along with the precise measurement of the domain wall velocity. The newly developed method is especially important now, when large effort is devoted to the development of domain wall logic devices based on ultrathin magnetic wires and nanowires.


CCAAT/enhancer binding protein and nuclear factor-Y regulate adiponectin gene expression in adipose tissue.
Adiponectin is one of the adipokines secreted by adipocytes and regulates energy homeostasis associated with insulin sensitivity, suggesting a possibility of nutritional regulation of adiponectin gene expression. In this study, we showed that the transcription of adiponectin gene was induced 4-6 h after refeeding of mice. Also, differentiated 3T3-L1 adipocytes that were treated with high glucose expressed significantly increased adiponectin mRNA. Promoter analysis using nuclear extracts from white adipose tissue revealed that CCAAT/enhancer binding protein (C/EBP) and nuclear factor-Y (NF-Y) bound on the -117/-73 region of the adiponectin promoter. This region was critical for the activity of the adiponectin promoter as the deletion or mutation of this region markedly diminished the promoter activity to a basal level. Furthermore, the C/EBP binding increased in both refed animal and high glucose-treated 3T3-L1 adipocytes in an electrophoretic mobility shift assay, suggesting that C/EBP is responsible for the dietary response of the adiponectin gene expression. Chromatin immunoprecipitation studies demonstrated the binding of C/EBP and NF-Y in both mouse and differentiated 3T3-L1 adipocytes and also that C/EBP binding increased in response to high glucose. These findings demonstrated that C/EBP and NF-Y are critical for the regulation of the adiponectin expression in response to nutrients and in the course of adipocyte differentiation.


A biometric authentication model using hand gesture images.
A novel hand biometric authentication method based on measurements of the user's stationary hand gesture of hand sign language is proposed. The measurement of hand gestures could be sequentially acquired by a low-cost video camera. There could possibly be another level of contextual information, associated with these hand signs to be used in biometric authentication. As an analogue, instead of typing a password 'iloveu' in text which is relatively vulnerable over a communication network, a signer can encode a biometric password using a sequence of hand signs, 'i' , 'l' , 'o' , 'v' , 'e' , and 'u'. Subsequently the features from the hand gesture images are extracted which are integrally fuzzy in nature, to be recognized by a classification model for telling if this signer is who he claimed himself to be, by examining over his hand shape and the postures in doing those signs. It is believed that everybody has certain slight but unique behavioral characteristics in sign language, so are the different hand shape compositions. Simple and efficient image processing algorithms are used in hand sign recognition, including intensity profiling, color histogram and dimensionality analysis, coupled with several popular machine learning algorithms. Computer simulation is conducted for investigating the efficacy of this novel biometric authentication model which shows up to 93.75% recognition accuracy.


Gender differences in cardiac rehabilitation patients.
Gender differences in anxiety, self-efficacy, activity tolerance, and adherence were assessed in 101 patients (80 males, 21 females) with coronary artery disease consecutively admitted to three phase II cardiac rehabilitation centers. The percentage of women in rehabilitation is 20% lower than anticipated based on coronary morbidity data. On admission to rehabilitation, men were significantly better able to tolerate physical activity, were less anxious, and perceived themselves as having greater efficacy in enduring exercise and activities of daily living than women. During the first month of rehabilitation, 24% of males and 33% of females missed 1 week or more of scheduled sessions. There were no significant differences in demographic or diagnostic characteristics between sexes.


Furanones and Anthranilic Acid Derivatives from the Endophytic Fungus Dendrothyrium variisporum.
Extracts from an endophytic fungus isolated from the roots of the Algerian plant Globularia alypum showed prominent antimicrobial activity in a screening for novel antibiotics. The producer organism was identified as Dendrothyrium variisporum by means of morphological studies and molecular phylogenetic methods. Studies on the secondary metabolite production of this strain in various culture media revealed that the major components from shake flasks were massarilactones D (1) and H (2) as well as two new furanone derivatives for which we propose the trivial names (5S)-cis-gregatin B (3) and graminin D (4). Scale-up of the fermentation in a 10 L bioreactor yielded massarilactone D and several further metabolites. Among those were three new anthranilic acid derivatives (5-7), two known anthranilic acid analogues (8 and 9) and three cyclopeptides (10-12). Their structures were elucidated on the basis of extensive spectroscopic analysis (1D- and 2D-NMR), high-resolution mass spectrometry (HRESIMS), and the application of the modified Mosher's method. The isolated metabolites were tested for antimicrobial and cytotoxic activities against various bacteria, fungi, and two mammalian cell lines. The new Metabolite 5 and Compound 9 exhibited antimicrobial activity while Compound 9 showed cytotoxicity activity against KB3.1 cells.


The Role of High-Content Complex Dietary Fiber in Medical Nutrition Therapy for Gestational Diabetes Mellitus.
Objectives: A controlled open clinical study was conducted to evaluate the role of Ricnoat, a high-content complex dietary fiber powder produced by Zhuhai Aimed Biotechnology Co. Ltd., in medical nutrition therapy (MNT) to treat gestational diabetes mellitus (GDM). The study aimed to investigate glycemic control, lipid control, weight control, and pregnancy outcomes (neonatal weight) in patients with GDM, as well as evaluate the clinical safety of Ricnoat. Methods: A total of 120 patients with GDM who were admitted to three hospitals in Shanghai between January 2019 and January 2020 were enrolled. Ricnoat was used for intervention for patients in the experimental group. Using a χ2 test and t-test, respectively, comparisons were conducted between the measurement data and countable data of the demographics and baseline disease characteristics of the experimental group and control group. Results: Fasting blood glucose, 2-h postprandial blood glucose, glycated hemoglobin, total cholesterol, triglycerides, low-density lipoprotein, maternal gestational weight gain, neonatal weight, serum creatinine, glutamate transaminase, and aspartate aminotransferase were lower in the experimental group than in the control group, whereas high-density lipoprotein was higher in the experimental group than in the control group. Ricnoat intervention resulted in satiety higher than the expected 80% and more common occurrence of type 4 (smooth and soft, like salami or a snake) and type 5 (a soft mass with clear edges) stools. Conclusion: Ricnoat intervention had a significant effect on glycemic control, lipid control, weight control, and pregnancy outcomes (neonatal weight) in patients with GDM by enhancing maternal satiety and improving the stool features of pregnant women. It was also found to be safe for application during pregnancy.


Treatment of severe infections caused by Staphylococcus aureus: a change in the vancomycin paradigm?
Staphylococcus aureus is a frequent agent of serious intensive care unit infections with high associated mortality rates. Resistance to methicillin is frequent, exceeding 50% in many countries, and for these strains, vancomycin is the agent of choice. Resistance to this drug is now frequent for Enterococcus, but low rates are reported for S. aureus. Nonetheless, treatment failures with vancomycin for infections caused by strains considered susceptible have been reported during recent years. This article aims to review the possible explanations for this phenomenon, which is challenging the old paradigm of S. aureus infections and vancomycin use.


A long-term open-label extension study assessing cognition and behavior, tolerability, safety, and efficacy of adjunctive levetiracetam in children aged 4 to 16 years with partial-onset seizures.
The objective of this study was to assess cognition and behavior in children (4-16 years; n = 103) with partial-onset seizures using the Leiter-R International Performance Scale and Achenbach Child Behavior Checklist. The study was a multicenter, open-label, noncomparative 48-week extension study (NCT00152516) of adjunctive levetiracetam (20-100 mg/kg/d, mean 50.2 mg/kg/d). Improvement from baseline in Leiter-R Memory Screen composite score at weeks 24 and 48 (mean [SD] change, +4.8 [12.6] and +4.5 [15.3]) was similar to changes observed with levetiracetam and placebo in a prior study. Child Behavior Checklist Syndrome scores improved from baseline at weeks 24 and 48 (total problems mean [SD] change, -9.3 [22.2] and -10.4 [23.4]). Adjunctive levetiracetam was well tolerated (most frequently reported central nervous system-related treatment-emergent adverse events: headache [24.3%], aggression [7.8%], irritability [7.8%]). Of the patients, 4.9% discontinued because of treatment-emergent adverse events. Levetiracetam provided good and sustained seizure control (median percentage reduction from baseline in partial-onset seizure frequency/wk during maintenance: 86.4%); 24.7% of patients had continuous seizure freedom from all seizure types for ≥40 weeks. In children, adjunctive levetiracetam was associated with long-term stability in cognitive functioning and improvement in emotional/behavioral functioning over time.


Interaction between perceived and imagined rotation.
In Experiment 1, subjects performed a mental-rotation task in which they were timed as they decided whether rotated letters were normal or backwards. Between presentations of the letters, they watched a rotating textured disk that induced an aftereffect of rotary movement on the letters. The function relating reaction times to orientation was influenced asymmetrically by the aftereffect, suggesting that perceived movement interacts with imagined movement. Experiment 2 showed that the aftereffect produced a negligible influence on perceived orientation, suggesting that the influence of the aftereffect on mental rotation was not caused by changes in the perceived orientations of the letters. Detailed analysis of the mental-rotation functions suggested that the aftereffect may sometimes have induced subjects to rotate letters through the larger rather than the smaller angle back to the upright where the aftereffect was in the appropriate direction.


Design and Application of A Bioluminescent Biosensor for Detection Of Toxicity Using Huh7-CMV-Luc Cell Line.
Cell-based biosensors (CBBs) are becoming important tools for biosecurity a lications and rapid diagnostics in food microbiology for their unique capability of detecting hazardous materials. Pollutants, such as heavy metals and chemicals, are now considered as a global threat and are associated with detrimental health outcomes. Fast and accurate detection of pollutants is essential to reduce these threats. In this study, the enhancer sequence of human cytomegalovirus (hCMV) IE genes cloned upstream of luc gene in PGL4.26 plasmid, in order to increase basal luciferase activity. This recombinant vector was transfected into Huh7 cell line and after 21 days of treatment with Hygromycin B selectable marker, stable cell line was generated. After several passages, cells containing this vector showed high luciferase activity in normal conditions without any induction following to overexpression of luc gene. Huh7-CMV-luc cell line was able to detect the slightest changes in ATP level, due to the effect of different toxins on the cell which disrupt cellular respiration and ATP production processes. In order to investigate the sensitivity of the cell line, the cells were incubated with 0.1-10 μM of chemical toxins affecting ATP production. These toxins affect luciferase activity in a dose dependent manner, with maximal sensitivity approximately about 0.2 μM to toxin concentrations. Additionally, this biosensor provided a rapid detection as early as 4 h in response to the toxicants. Whole cell biosensors like huh7-CMV-luc cell line can be considered as a powerful tool for the sensitive and efficient monitoring of general toxins, drugs, and environmental pollutants.


Pharmacokinetics and pharmacodynamics of L-Dopa after acute and 6-week tolcapone administration in patients with Parkinson's disease.
Tolcapone, a central and peripheral catechol O-methyltransferase (COMT) inhibitor, reduces the conversion of L-Dopa into 3-O-methyl-Dopa (3-OMD), thus leading to more stable and sustained L-Dopa plasma levels. This study was designed to evaluate the effects of acute and 6-week tolcapone administration on L-Dopa pharmacokinetics and pharmacodynamics in Parkinson's disease (PD) patients with predictable motor fluctuations. Tapping test, walking time, and tremor, as well as L-Dopa and 3-OMD plasma levels, were assessed before and for 5 hours after the administration of a single L-Dopa dose, alone or in combination with 200 mg tolcapone, in seven patients with PD. This clinical and pharmacokinetic study was repeated after 6 weeks of tolcapone therapy (200 mg three times daily). It was observed that tolcapone, after both acute and chronic administration, prolonged the motor improvement induced by L-Dopa. As a result, at week 6 of tolcapone therapy, the daily hours spent "off" were significantly decreased. Tolcapone significantly increased the area under the curve of L-Dopa plasma levels by slowing down the elimination of L-Dopa from plasma, whereas the maximal concentration of L-Dopa was not modified. 3-OMD levels decreased significantly after acute tolcapone administration, and after 6 weeks of tolcapone therapy, they were approximately one sixth of pre-tolcapone values. The data confirm that tolcapone decreases L-Dopa clearance and prolongs motor response in PD patients with motor fluctuations, and that this effect is maintained after 6 weeks of tolcapone therapy.


Geographically indirect immigration to Canada: description and analysis.
"This article is concerned with geographically indirect immigration to Canada over the period 1968-1988. A geographically indirect immigrant is an individual legally admitted to Canada whose country of last permanent residence differs from country of birth. Records maintained by Employment and Immigration Canada on every immigrant legally admitted over the period were used in the study. Relative to geographically direct immigrants, geographically indirect immigrants tend to be older, more educated, and more highly skilled. Moreover, if they were not born in an English or French speaking country, indirect immigrants are more likely to speak English and/or French capably than direct migrants born in such countries. The study also contains bivariate logit estimates of a model of geographically indirect Canadian immigration. This model suggests that indirect migrants tend to be influenced by personal characteristics (age, sex, marital status, occupation, language ability), as well as by various characteristics of the country of birth (distance from Canada, income level, political conditions)."


Intraoperative ultrasound in gastrointestinal cancer. An analysis of 272 operated patients.
Diagnostic efficacy of the intraoperative ultrasound was compared with pre- and postoperative ultrasound, and with the intraoperative surgical examination. The prospective study of 272 patients with the cancer of esophagus, stomach, duodenum, colon and rectum was performed. In 103 patients (37.8%) intraoperative ultrasound identified oncological pathology in the liver, other parenchymal organs, lymph nodes or local invasion of the cancer. Sixty-nine liver metastases were found in 45 patients and in 21 patients (7.7%) only intraoperative sonography discovered these deposits. The diagnostic efficacy value of this method in detecting liver metastases is much higher than preoperative ultrasound and intraoperative palpation. Intraoperative ultrasonography, as the only method, has shown local tumor invasion in 13 patients (4.8%) and metastatic lymph nodes in 8 patients (2.9%). In 53 patients (19.5%) information gathered from intraoperative sonography, caused modification of the surgical procedure. These data show that intraoperative ultrasound is a simple, cheap and useful clinical technique, which can examine not only the liver, but also the tumor and lymph node areas. The method is also very effective in assessment of the completeness of the range of adequate primary tumor resection.


The inhibitory function of CTLA-4 does not require its tyrosine phosphorylation.
CTLA-4 is a negative regulator of T cell responses. Sequence analysis of this molecule reveals the presence of two cytoplasmic tyrosine residues at positions 165 and 182 that are potential Src homology (SH)-2 domain binding sites. The role of phosphorylation of these residues in CTLA-4-mediated signaling is unknown. Here, we show that sole TCR ligation induces zeta-associated protein (ZAP)-70-dependent tyrosine phosphorylation of CTLA-4 that is important for cell surface retention of this molecule. However, CTLA-4 tyrosine phosphorylation is not required for down-regulation of T cell activation following CD3-CTLA-4 coengagement. Specifically, inhibition of extracellular signal-regulated kinase (ERK) activation and of IL-2 production by CTLA-4-mediated signaling occurs in T cells expressing mutant CTLA-4 molecules lacking the cytoplasmic tyrosine residues, and in lck-deficient or ZAP-70-deficient T cells. Therefore, CTLA-4 function involves interplay between two different levels of regulation: phosphotyrosine-dependent cell surface retention and phosphotyrosine-independent association with signaling molecules.


MAP kinases and cell migration.
Recent studies have demonstrated that mitogen-activated protein kinases (MAPKs), including Jun N-terminus kinase (JNK), p38 and Erk, play crucial roles in cell migration. JNK, for example, regulates cell migration by phosphorylating paxillin, DCX, Jun and microtubule-associated proteins. Studies of p38 show that this MAPK modulates migration by phosphorylating MAPK-activated protein kinase 2/3 (MAPKAP 2/3), which appears to be important for directionality of migration. Erk governs cell movement by phosphorylating myosin light chain kinase (MLCK), calpain or FAK. Thus, the different kinases in the MAPK family all seem able to regulate cell migration but by distinct mechanisms.


Antithyroid drug regimens before and after 131I-therapy for hyperthyroidism: evidence-based?
In view of the new national guideline on thyroid dysfunction, the evidence base for current practice as well as the new guideline is assessed with regard to the use of antithyroid drugs (ATDs) before and after radioiodine (131I) therapy. In December 2006, we surveyed 16 hospitals by telephone about different aspects of their antithyroid drug regimen: all eight academic centres and eight nonacademic teaching hospitals. The literature was searched for an evidence-based answer to each question in the inquiry. 13 of 16 hospitals (81%) use antithyroid drugs for pretreatment before 131I. ATDs are discontinued on average four days before 131I or diagnostic scan. However, 27% stop only three days beforehand, which may diminish the effect of 131I. Propylthiouracil (PTU) is also withdrawn four days before 131I, although the literature shows that PTU diminishes the effect of 131I even if it is stopped 15 days beforehand. Resumption of ATDs after 131I to prevent thyrotoxicosis is common practice (81%). One hospital (6%) never restarts ATDs, two (13%) only by indication. Adjunctive treatment consists of combination therapy in 93%, is usually resumed within two days after 131I therapy, and then continued for two to six months. Routine adjunctive treatment is not evidence-based and may be limited to a high-risk subset, especially elderly patients (>70 years) and patients with cardiac comorbidity. Resumption of ATDs within five to seven days after 131I may diminish the effect of 131I. Antithyroid drug regimens in the Netherlands are heterogeneous. The evidence base of current practice and the new guideline are discussed.


Influence of resuspension on the fate of fecal indicator bacteria in large-scale flumes mimicking an oligotrophic river.
In this study, large-scale flume systems simulating an oligotrophic river were used to explore the fate and transport of the fecal indicator bacteria (FIB) Escherichia coli and enterococci following a combined sewer overflow (CSO). Specifically, the removal pattern of FIB from the water column was examined as well as deposition onto the flume bed. Finally, the impact that a sudden increase in bed shear stress has on FIB in the water column was investigated. The large-scale flumes utilized in this study proved extremely useful for our investigations as they very closely approximated conditions within the Isar River (Munich, Germany). By using both natural substratum and fresh river water, as well as a flow velocity of nearly 1 m s(-1) at a water depth of roughly 0.5 m, shear stresses typical of the Isar River (9 N m(-2)) were achieved. As a result, scaling effects were appreciably reduced. In our flume system, UV inactivation played only a minimal role in overall FIB removal. Therefore, we were able to more precisely investigate other mechanisms which result in FIB removal from the water column. From the two standard FIB removal experiments following a CSO, the removal rate coefficient (k) of 0.2 h(-1) was identified for both E. coli and enterococci in the water column. An increase in the bed shear stress led to more than a 150% rise in total suspended solid (TSS) levels in the water column. These elevated TSS levels (≈ 50 mg l(-1)) increased the persistence of suspended FIB in the water column by 20 h (k = 0.05 h(-1)). This indicates that higher TSS loads resulting from resuspended bed sediments can significantly expand the area that is impacted by a CSO event. At lower TSS loads (<20 mg l(-1)) deposition onto the flume bed did not contribute significantly to FIB removal from the water column. Any deposition which did occur did not result in a net accumulation of culturable FIB in the benthic biofilm.


The Ground-Based BIOMEX Experiment Verification Tests for Life Detection on Mars.
The success of an astrobiological search for life campaign on Mars, or other planetary bodies in the Solar System, relies on the detectability of past or present microbial life traces, namely, biosignatures. Spectroscopic methods require little or no sample preparation, can be repeated almost endlessly, and can be performed in contact or even remotely. Such methods are therefore ideally suited to use for the detection of biosignatures, which can be confirmed with supporting instrumentation. Here, we discuss the use of Raman and Fourier Transform Infrared (FT-IR) spectroscopies for the detection and characterization of biosignatures from colonies of the fungus Cryomyces antarcticus, grown on Martian analogues and exposed to increasing doses of UV irradiation under dried conditions. The results report significant UV-induced DNA damage, but the non-exceeding of thresholds for allowing DNA amplification and detection, while the spectral properties of the fungal melanin remained unaltered, and pigment detection and identification was achieved via complementary analytical techniques. Finally, this work found that fungal cell wall compounds, likely chitin, were not degraded, and were still detectable even after high UV irradiation doses. The implications for the preservation and detection of biosignatures in extraterrestrial environments are discussed.


Cytokinin-induced root growth involves actin filament reorganization.
Root architecture is developmentally plastic and affected by many intrinsic factors (e.g. plant hormones) and extrinsic factors (e.g. touch, gravity) in order to maximize nutrient and water acquisition. We have recently shown that asymmetrical exposure of cytokinin (CK) at the root tip causes root growth directional changes that is dependent on ethylene signaling and is potentiated by glucose signaling. Auxin homeostasis as maintained by auxin signaling and transport is also involved in CK-induced root cell elongation and differential growth. The signaling pathways eventually converge at actin filament organization since actin filament organization inhibitor latrunculin B (Lat B) can also induce similar growth. We, show that CK can actually alter actin filament organization as seen in actin binding protein 35S::GFP-ABD2-GFP transgenic lines as is also altered by auxin polar transport inhibitor 1-N-naphthylphthalamic acid (NPA) and Lat B in different manners.


Assessment of therapy in gestational diabetes by substrate and hormone responses to a standardized test meal.
Postprandial substrate and hormone responses to a standard mixed meal (400 kcal) was determined at two occasions, A and B, in 11 women with gestational diabetes (GDMs) and 11 normoglycaemic controls, matched for age, body mass index, and gestational age. Levels of circulating glucose, non-esterified fatty acids (NEFA), glycerol, 3-hydroxybutyrate (3-HBA), individual amino acids, insulin, and C-peptide were analysed. A was performed when GDMs were considered inadequately controlled with diet alone, B later during gestation following initiation of insulin therapy because of hyperglycaemia. Fasting glucose, glycerol, total and individual amino acids (alanine, valine, isoleucine, leucine), insulin, and C-peptide were not different from normal during A and B, neither were postprandial amino acid levels. During test A, GDMs had elevated fasting and postprandial 3-HBA (p < 0.001), greater postprandial rise of glucose (p < 0.001), elevated NEFA (p < 0.05), but normal and parallel decreases of NEFA and glycerol. Insulin and C-peptide responses were delayed and prolonged. During B, GDMs had higher glucose response (p < 0.005), higher fasting 3-HBA (p < 0.02) but similar and parallel decreases of NEFA, glycerol, and 3-HBA as controls. The C-peptide response was not significantly different from normal; insulin response was higher (p < 0.05). In conclusion, the relative insulin deficiency characterizing GDMs, also when treated with insulin, is associated with selected defects in insulin action; mainly affecting glucoregulation, whereas suppression of lipolysis and proteolysis remain normal.


Outpatient treatment for acute uncomplicated diverticulitis.
Traditionally, treatment of acute diverticulitis has mostly been based on inpatient care. The question arises whether these patients can be treated on an outpatient basis as the admissions for diverticular disease have been shown to be increasing every year. We studied whether outpatient treatment of acute uncomplicated diverticulitis is feasible and safe, and which patients could benefit from outpatient care. A retrospective cohort study was carried out in two teaching hospitals using hospital registry codes for diverticulitis. All patients diagnosed with acute uncomplicated diverticulitis between January 2004 and January 2012, confirmed by imaging or colonoscopy, were included. Exclusion criteria were patients with recurrent diverticulitis, complicated diverticulitis (Hinchey stages 2, 3, and 4), and right-sided diverticulitis. Inpatient care was compared with outpatient care. Primary outcome was admission for outpatient care and the complication rate in both groups. Multivariate analysis was carried out to identify potential factors for inpatient care. Of 627 patients with diverticulitis, a total of 312 consecutive patients were identified with primary uncomplicated diverticulitis of the sigmoid colon; 194 patients had been treated as inpatients and 118 patients primarily as outpatients. In this last group, 91.5% had been treated successfully without diverticulitis-related complications or the need for hospital admission during a mean follow-up period of 48 months. Despite inherent patient selection in a retrospective cohort, ambulatory treatment of patients presenting with uncomplicated acute diverticulitis seems feasible and safe. In mildly ill and younger patients, hospital admission can be avoided.


Structure and function of axo-axonic inhibition.
Inhibitory neurons in mammalian cortex exhibit diverse physiological, morphological, molecular, and connectivity signatures. While considerable work has measured the average connectivity of several interneuron classes, there remains a fundamental lack of understanding of the connectivity distribution of distinct inhibitory cell types with synaptic resolution, how it relates to properties of target cells, and how it affects function. Here, we used large-scale electron microscopy and functional imaging to address these questions for chandelier cells in layer 2/3 of the mouse visual cortex. With dense reconstructions from electron microscopy, we mapped the complete chandelier input onto 153 pyramidal neurons. We found that synapse number is highly variable across the population and is correlated with several structural features of the target neuron. This variability in the number of axo-axonic ChC synapses is higher than the variability seen in perisomatic inhibition. Biophysical simulations show that the observed pattern of axo-axonic inhibition is particularly effective in controlling excitatory output when excitation and inhibition are co-active. Finally, we measured chandelier cell activity in awake animals using a cell-type-specific calcium imaging approach and saw highly correlated activity across chandelier cells. In the same experiments, in vivo chandelier population activity correlated with pupil dilation, a proxy for arousal. Together, these results suggest that chandelier cells provide a circuit-wide signal whose strength is adjusted relative to the properties of target neurons.


Fatal late onset group B streptococcal meningitis following maternal postpartum sepsis.
Although maternal screening and the administration of prophylactic intrapartum antibiotics have decreased the incidence of early onset group B streptococcal (GBS) disease in neonates, there is still significant morbidity and mortality as a result of neonatal GBS disease.Maternal GBS infections are not uncommon, but with appropriate therapy there is almost a uniformly good outcome. Little is written about the appropriate management of well infants born to mothers with postpartum GBS sepsis.The question of whether well infants born to mothers with GBS puerperal sepsis should be treated empirically with antibiotics and the lack of literature concerning this issue became apparent when an untreated term infant died of late onset GBS meningitis following maternal puerperal GBS sepsis. We describe this event in the following case presentation.With the current paucity of literature regarding the management of well infants born to mothers with postpartum GBS sepsis, it seems prudent to treat such infants empirically with antibiotics (following a full septic work-up) until this matter has been investigated further.


Identification of secreted antigen 3 from Babesia gibsoni.
A cDNA expression library of Babesia gibsoni was screened with the serum collected from a dog experimentally infected with B. gibsoni. A novel antigen sharing homology with secreted antigen 1 of B. gibsoni was isolated. The genomic analysis indicated that the BgSA3 gene exists as multicopies in the genome of B. gibsoni. The putative peptide encoded by the BgSA3 gene showed some characteristics of secreted proteins. The serum raised in mice immunized with the recombinant BgSA3 expressed in Escherichia coli could recognize a native parasite protein with a molecular mass of 70 kDa. Moreover, a sandwich enzyme-linked immunosorbent assay with anti-BgSA3 antibodies could detect the circulating BgSA3 in the blood plasma of dogs experimentally infected with B. gibsoni. The identification of BgSA3 provided a useful target for the development of a diagnostic test for detecting specific antibodies and circulating antigens.


PROGNOSIS AND PREVENTION OF UTERUS BLEEDINGS IN EARLY POSTPARTUM PERIOD FOR WOMEN WITH IDIOPATHIC ARTERIAL HYPOTENSION.
The aim: To establish the effectiveness of thromboelastography (TEG) and tranexamic acid (TXA) for prognosis and prevention of early postpartum period bleedings (PPB) for postpartum women with idiopathic arterial hypotension (IAH). Materials and methods: Coagulogical research was conducted (coaugologram screening, dynamic function of platelets under the influence of adenosine diphosphate (ADP) (visual assessment), measurement of soluble fibrin-monomer complexes (FMC) and TEG of 36 in parturient women during the I chilbirth period with arterial hypotension. 14 parturient women with normal fibrinolysis were included into the first observation group; The second group includes 22 parturient women with TEG results which show signs of hyperfibrinolysis. Further, in cases when stronger fibrinolysis was detected during the late pushing phase of childbirth period, the TXA by amount of 1,0 g IV (bolus) was injected due to bleeding prevention. TEG was repeated during early postpartum period. Results: the inhibition of platelet aggregation activity with ADP was observed in every parturient woman with IAH in the first partum period. In 61,1% cases with TEG hyperfibrinolysis were shown, which was accompanied by significant increase in FMC levels in blood. The use of TXA as PPB prevention for parturient women with IAH and hyperfibrinolysis during TEG was fully oppressing the fibrinolytic activity and was not affecting the coagulation part of hemostasis. Conclusions: hemostasis testing during childbirth based on TEG gives the ability to prognose the hemorrhagic complications in parturient women with IAH and administer their prophylaxy using TXA.


[Trimethoprim in the therapy of symptomatic liver porphyria].
Administration of antimalaria drugs to patients with symptomatic hepatic porphyria (porphyria cutanea tarda) at the First Medical Clinic made it possible due to previous experimental studies, to influence the porphyrim metabolism of yeasts. The effect of trimetoprim was investigated in clinical work in 12 hitherto not treated patients with the manifest form of symptomatic hepatic porphyria. The group comprised 9 men, mean age 56.4 years, and 3 women mean age 43.6 years. During the two-year clinical study dermatological symptoms of the disease became milder or receded. Concurrently there was a significant regression of porphyrinuria. In the whole group porphyrinuria declined to 11% of the original values. The porphyrin content of hepatic tissue declined considerably after two years treatment. In the group as a whole to 40% of the original values. Trimetoprim is another drug which influences porphyrin metabolism. The authors did not detect any undesirable side-effects of trimetoprim treatment. The effect of trimetoprim on clinical and biochemical parameters of the disease is less marked than the effect of chloroquine. This new treatment can be used in patients resistant to chloroquine or in combination with other anti-malaria drugs.


Disarming batterers through restraining orders: the promise and the reality in California.
Laws that prohibit persons under a domestic violence restraining order from purchasing or possessing a firearm are a primary way to keep guns out of the hands of batterers. In July 2005, the California Attorney General's Task Force on the Local Criminal Justice Response to Domestic Violence issued a report called Keeping the Promise: Victim Safety and Batterer Accountability. The report focused, in part, on the extent to which California's domestic violence restraining order system succeeds in disarming batterers. Restraining orders are the principal means by which the criminal justice system can accomplish this objective. The Task Force found that criminal justice agencies and the courts performed poorly in this area. The report strongly recommended that a more strategic, collaborative use of laws already on the books could significantly improve performance, without much additional expense. What follows is a summary of those finding and recommendations.


Neurochemical features of idiopathic restless legs syndrome.
The most important traditional hypotheses of the pathogenesis of idiopathic restless legs syndrome (iRLS) involve dopaminergic dysfunction and iron deficiency. However, a possible role of other neurotransmitter or neuromodulators, mainly glutamate, gamma-hydroxybutyric acid (GABA), and adenosine have been suggested in recent reports. Moreover, iron deficiency in experimental models (which causes sensorimotor symptoms resembling those of RLS) is able to induce changes in dopaminergic, glutamatergic and adenosinergic neurotransmission, thus suggesting its crucial role in the pathogenesis of this disease. Relationship between iRLS and opiates, oxidative stress and nitric oxide, and with vitamin D deficiency has also been reported, although data regarding these variables should be considered as preliminary. In this review, we focus on studies relating to neurochemical findings in iRLS.


Effluent levels of thrombomodulin predict early graft function in clinical liver transplantation.
Thrombomodulin is a surface protein on vascular endothelial cells that serves as a binding site for thrombin and plays an important role as an anticoagulant factor. We correlated plasma thrombomodulin levels with early graft function after liver transplant in 58 recipients. Blood samples were collected at the following time points: before surgery, just before reperfusion, 30, 60, 120 min after reperfusion, and post-operative day 1. The first and last 20 cc of caval effluent were also collected. Plasma thrombomodulin levels were measured by a sandwich enzyme-binding assay in the blood samples; tissue expression was determined by immunohistochemistry. Poor early graft function was defined as peak aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2500 U/l during the first 3 post-operative days and prothrombin time >16 s on post-operative day 2. Thrombomodulin levels in the first 20 cc of caval effluent ranged from 1.33 to 91 FU/ml and showed a significant positive correlation with ischemic time, intra-operative blood transfusion requirement, and early graft function. In grafts with high effluent thrombomodulin (>20 FU/ml, n=12), the incidence of poor early graft function and primary nonfunction was 66.7% and 25.0%, respectively; in grafts with low effluent thrombomodulin (<20 FU/ml, n=46), graft function was not impaired. By immunohistochemistry, thrombomodulin was detected in large vessels of every donor liver. Sinusoidal cells, however, showed positive staining only in livers with poor early graft function. Effluent thrombomodulin levels reflect the extent of preservation injury and might be a useful marker for predicting graft function after liver transplantation.


Predicted critical environmental concentrations for 500 pharmaceuticals.
A growing number of pharmaceuticals are found in surface waters worldwide, raising concerns about their effects on aquatic organisms and it is a major challenge to develop a rational strategy for prioritizing drugs on which to focus the most extensive environmental research efforts. However, in contrast to most other chemicals, very good understanding of the human potency of pharmaceuticals has been obtained through efficacy and safety testing. Assuming that a drug acts primarily through the same target(s) also in a non-target species, it would be possible to predict the likelihood for pharmacological interactions in wildlife. Among aquatic organisms, fish most often share drug targets with humans. In this study, we have calculated the predicted critical environmental concentration (CECs), i.e. the surface water concentration expected to cause a pharmacological effect in fish, for 500 pharmaceuticals, assuming equivalent pharmacological activity. The CECs are based on literature data on human potencies together with a predicted bioconcentration factor in fish for each drug based on lipophilicity. We propose that CECs could be used as preliminary indicators of specific drugs' potential to cause adverse pharmacological effects at specific water concentrations, used when selecting pharmaceuticals to include in screening campaigns and for assessing relevant detection limits.


Confounding of alternate respiration by lipoxygenase activity.
The initial burst of respiratory activity (Q(o) (2)) of imbibing soybean (Glycine max [L.] Merr. var. Wayne) seed tissue is cyanide-insensitive, and sensitive to salicylhydroxamate: presumptive evidence for the presence of alternate respiration. The initial O(2) consumption is also highly sensitive to propyl gallate. Soybean lipoxygenase exhibits similar characteristics of insensitivity to cyanide and sensitivity to salicylhydroxamate and to propyl gallate. The initial burst of respiration is enhanced by the addition of linoleic acid, a lipoxygenase substrate. These results indicate that the conventional tests for alternate respiration in plant tissues can be confounded by lipoxygenase; they also suggest that propyl gallate can be used to assess the possible participation of lipoxygenase in the O(2) uptake by plant tissues.


[Influence of initial admission department for coronary arteriography on choice of mode of coronary revascularization].
To investigate the influence of initial admission department for coronary arteriography on the choice of mode of coronary revascularization. From October 2003 to June 2004 2156 patients with coronary heart disease were admitted into the department of internal medicine (1667 cases) or department of surgery (489 cases) to undergo coronary arteriography (CAG) and coronary revascularization. The influence of the initial admission departments on the choice of mode of coronary revascularization for the patients with different clinical manifestations and angiographic characteristics, including one-vessel disease, two-vessel disease, three-vessel disease, and multi-vessel disease of different types was analyzed. 1336 (80.1), 326 (19.6%), and 5 (0.3%) of the 1667 patients initially admitted to the department of internal medicine, received percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), and CABG + PCI respectively with a complete revascularization rate of 63.3%. 52 (10.6%) and 437 (89.4%) of the 489 patients initially admitted to the department of surgery received PCI and CABG respectively with a complete revascularization rate of 75.5%. The CABG rates for the patients different types of lesion were all significantly higher in the patients initially admitted to the department of surgery than in the patients initially admitted in the department of internal medicine (all P < 0.05). The in-hospital death rate, new-onset myocardial infarction rate, and main adverse cardio-cerebral event rate of the patients admitted into the department of surgery were 3.9%, 1.8%, and 5.7% respectively, all significantly higher than those of the patients initially admitted in the department of internal medicine (1.2%, 0.5%, and 1.5% respectively, all P < 0.01). Logistic regression showed that initial admission into department of surgery, number of diseased vessels, left main trunk disease, proximal descending anterior branch disease, and chronic total occlusion rate were independent predictor for choice of CABG (all P < 0.01). Cardiologists are more likely to choose PCI and cardiac surgeons are more likely to choose CABG. It is imperative to collect more evidence-based data so as to develop guidelines for the choice of reasonable mode of revascularization.


Regulation of lens connexin 45.6 by apoptotic protease, caspase-3.
Gap junctions are important in maintaining lens homeostasis. Here we report that connexin 45.6 (Cx45.6) was partially truncated to a 46 kDa fragment during chicken lens development. This specific truncation initiated during embryonic days and the truncated fragment accumulated towards the later developmental stages. When membranes of the embryonic lens were subjected to caspase-3 treatment, the 46 kDa fragment of Cx45.6 was reproduced, suggesting apoptotic protease caspase-3 is a potential protease involved. The COOH-terminus of Cx45.6 in GST-fusion protein was also cleaved by caspase-3, confirming that Cx45.6 is a direct substrate of caspase-3. Induction of apoptosis in lens primary cultures regenerated the 46 kDa fragment and this cleavage was blocked by a caspase-3 inhibitor. Alteration of amino acid residue Asp364 or Glu367 to Ala prevented Cx45.6 from cleavage by caspase-3, suggesting that the cleavage site of Cx45.6 is likely to be between Glu367 and Gly361. Phosphorylation of Ser363, a known substrate for casein kinase II (CKII) in vivo, inhibited the cleavage of Cx45.6 by caspase-3. Thus, this study demonstrates that a lens connexin can be a direct target of caspase-3 and the cleavage by caspase-3 leads to the development-associated truncation of Cx45.6. Finally, caspase-3 mediated truncation can be modulated by the specific connexin phosphorylation.


Faecopneumothorax Caused by Perforated Diaphragmatic Hernia.
Incarcerated diaphragmatic hernias with intrathoracic perforation of the colon is a very rare but serious surgical emergency. A 78-year-old male patient presented to our emergency department with severe abdominal pain. A computer tomography (CT) scan revealed herniation of the left transverse colon and spleen into the thorax with colon perforation and fecal contents in the thoracic cavity. An emergent laparotomy confirmed the radiological diagnosis and showed a 6 cm dehiscence of the left diaphragm with strangulation of the left transverse colon as well as the spleen. A left-sided hemicolectomy with terminal transversostomy and splenectomy were performed. The diaphragm was closed with interrupted nonabsorbable sutures. We abstained from reinforcement of the suture line with a mesh because of the feculent contamination of the abdominal cavity. After extensive thoracoscopic lavage and insertion of two chest tubes, the patient was transferred to the intensive care unit. Diaphragmatic hernia even after a mild chest trauma can cause fatal complications. Diagnosis and treatment can be challenging and an interdisciplinary approach is recommended. Due to the associated comorbidity and long-lasting sequelae, we believe the awareness of this rare pathology as a differential diagnosis is important; both as an abdominal and thoracic emergency.


An Eye Toward Improving: A new training approach in ophthalmic anesthesia provides qualitative and quantitative feedback.
In ophthalmic anesthesia administration prior to surgeries for problems such as cataracts or glaucoma, the training of new doctors, as in other surgical specialties, is based on a model in which a student trains on a patient under the expert supervision of an experienced doctor. However, the traditional apprenticeship approach is problematic in eye surgery because ocular structures could potentially be damaged by those administering ophthalmic anesthesia for the first time. Apart from the obvious risk to patients, there is also the inability to quantify the performance of a trainee. One solution to these problems might be found in the development of a manikin-based ophthalmic anesthesia training system that can emulate the human ocular anatomy while providing real-time quantitative and qualitative feedback to the trainee during training.


The outcome of postoperative radiation therapy following plastic surgical resection of recurrent ear keloid: a single institution experience.
Ear keloids are abnormal continuously growing healing process following cutaneous injury. Surgical excision is the standard treatment strategy; however, 50-80% of cases develop recurrence. Adjuvant radiotherapy (RT) is commonly offered with a marked decrease in the recurrence rate. The variation in RT protocols used in different studies leads to a bias of results analysis. The aim is to present our experience of using surgical excision with postoperative radiotherapy for recurrent ear keloids. Also, studying different variables especially dose and keloid size that affects recurrence rate. Radiotherapy complications were reported and assessed. Keloids between 2006 and 2021 were retrospectively reviewed. Fifty-five ear keloids out of 83 cases who received RT after surgical excision were included in the study. Different dose regimens including 13 Gy/1fx, 8 Gy/1fx, 10 Gy/2fx, 15 Gy/3fx, and other fractionated regimens were used. The Median follow-up period was 35 months. Recurrence-free rate (RFR), side effects, and prognostic factors were assessed. The overall 2-year RFR was 88 ± 5%. The 2-year RFR was 83 ± 8% for dose regimens with biological effective dose (BED) ≤ 40 and 92 ± 5% for regimens with BED > 40 Gy with an insignificant p value. The 2-year RFR was 74 ± 10% compared to 97 ± 3% for keloids > 2 cm and keloids ≤ 2 cm respectively (p value 0.02). The higher dose used for keloids with > 2 cm size significantly improved RFR. The orthovoltage therapy showed marginally better 2-year RFR compared to electron beam therapy; however, statistically insignificant (p value 0.09). The side effects were minimal with no reported second malignancy or serious G3-4 complications. Excision followed by RT is a safe and effective treatment for recurrent ear keloids. Low and modest radiation doses are effective; however, a higher dose is recommended for keloids > 2 cm. We recommend a prospective larger-scale study to test the effect of dose and keloid size on the treatment results.


POSTOPERATIVE COMPLICATIONS WITH GLYCINE AND STERILE DISTILLED WATER AFTER TRANSURETHRAL RESECTION OF PROSTATE.
Transurethral resection of prostate (TURP) is considered the gold standard for the surgical treatment of BPH. Irrigant fluid absorption by the patient is a potentially serious complication of TURP and can lead to dilutional hyponatremia and TURP syndrome. Other common complications of TURP include urinary tract infection and secondary haemorrhage. The objective of this study was to compare the frequency of postoperative complications (Urinary Tract infection and dilutional hyponatremia) between 1.5% glycine and sterile distilled water used as irrigant in BPH patients after TURP. This randomized controlled trial was conducted in department of Urology, PIMS Islamabad, from August 2013 to February 2014. A total of 170 adult male patients between 50-80 years of age undergoing TURP with prostate volume more than 30cc on ultrasound. 85 patients each were randomly allocated to two groups. In group-A, glycine was used as irrigan,t solution during TURP while in group-B distilled water was used. Serum sodium levels were measured at 6th postoperative hour to look for dilutional hyponatremia. On the 15th postoperative day they were inquired about any clinical features of urinary tract infection. Also urine routine examination was performed to look for the presence of WBCs in the urine. Post-operative dilutional hyponatremia was observed in 13 (15.3%) patients in Group A and in 10 (11.8%) patients in group-B. The difference between both the groups being nonsignificant (p-value=0.501).Frequency of postoperative urinary tract infection on 15th postoperative day in group-A was 23(27.1%) while in group-B it was 16 (18.8%), the difference among both the groups being insignificant (p-value=0.202). Although the frequency of postoperative complications like UTI and dilutional hyponatremia was less with sterile distilled water, yet, the difference was statistically not significant.


Analysis of the cause of recurrent pregnancy loss in Vietnam: A cross-sectional study.
Recurrent pregnancy loss (RPL) is a physical and mental burden for women. In Vietnam, exploring the cause of miscarriages is still a challenge to clinical physicians. We aimed to investigate the etiology of RPL in the National Hospital of Obstetrics and Gynecology in Vietnam from 2012 to 2014. The cross-sectional study included 301 pregnant women with a history of RPL. The patients were examined and offered medical testing to determine the cause(s). Based on the testing, we determined causation for (11.29%) patients who had positive scores on an antiphospholipid antibody test and who were subsequently successfully treated for their problem.