Comparing Cortical Plasticity Induced by Conventional and High-Definition 4 × 1 Ring tDCS: A Neurophysiological Study

BackgroundTranscranial direct current stimulation (tDCS) induces long-lasting NMDA receptor-dependent cortical plasticity via persistent subthreshold polarization of neuronal membranes. Conventional bipolar tDCS is applied with two large (35 cm²) rectangular electrodes, resulting in directional modulation of neuronal excitability. Recently a newly designed 4 × 1 high-definition (HD) tDCS protocol was proposed for more focal stimulation according to the results of computational modeling. HD tDCS utilizes small disc electrodes deployed in 4 × 1 ring configuration whereby the physiological effects of the induced electric field are thought to be grossly constrained to the cortical area circumscribed by the ring.ObjectiveWe aim to compare the physiological effects of both tDCS electrode arrangements on motor cortex excitability.MethodstDCS was applied with 2 mA for 10 min. Fourteen healthy subjects participated, and motor cortex excitability was monitored by transcranial magnetic stimulation (TMS) before and after tDCS.ResultsExcitability enhancement following anodal and a respective reduction after cathodal stimulation occurred in both, conventional and HD tDCS. However, the plastic changes showed a more delayed peak at 30 min and longer lasting after-effects for more than 2 h after HD tDCS for both polarities, as compared to conventional tDCS.ConclusionThe results show that this new electrode arrangement is efficient for the induction of neuroplasticity in the primary motor cortex. The pattern of aftereffects might be compatible with the concept of GABA-mediated surround inhibition, which should be explored in future studies directly.     

Human Mannose-Binding Protein Inhibits Infection of HeLa Cells by Chlamydia trachomatis

The role that collectin (mannose-binding protein) may play in the host’s defense against chlamydial infection was investigated. Recombinant human mannose-binding protein was used in the inhibition of cell culture infection by Chlamydia trachomatis (C/TW-3/OT, E/UW-5/Cx, and L₂/434/Bu), Chlamydia pneumoniae (AR-39), and Chlamydia psittaci (6BC). Mannose-binding protein (MBP) inhibited infection of all chlamydial strains by at least 50% at 0.098 μg/ml for TW-3 and UW-5, and at 6.25 μg/ml for 434, AR-39, and 6BC. The ability of MBP to inhibit infection with strain L₂ was not affected by supplementation with complement or addition of an L₂-specific neutralizing monoclonal antibody. Enzyme-linked immunosorbent assay and dot blot analyses showed MBP bound to the surface of the organism to exert inhibition, which appeared to block the attachment of radiolabeled organisms to HeLa cells. Immunoblotting and affinity chromatography indicated that MBP binds to the 40-kDa glycoprotein (the major outer membrane protein) on the outer surface of the chlamydial elementary body. Hapten inhibition assays with monosaccharides and defined oligosaccharides showed that the inhibitory effects of MBP were abrogated by mannose or high-mannose type oligomannose-oligosaccharide. The latter carbohydrate is the ligand of the 40-kDa glycoprotein of C. trachomatis L₂, which is known to mediate attachment, suggesting that the MBP binds to high mannose moieties on the surface of chlamydial organisms. These results suggest that MBP plays a role in first-line host defense against chlamydial infection in humans.     

High‐Heteronucleobase‐Content Polystyrene Copolymers Prepared Using Click Chemistry Form Supramolecular Structures With Melamine Through Complementary Multiple Hydrogen‐Bonding Interactions

Free‐radical copolymerization is used to synthesize poly[styrene‐co‐(4‐vinylbenzyl azide)] (PS‐co‐PVBN₃), followed by click chemistry to react it with propargyl thymine (PT) to obtain a series of high‐performance polystyrene derivatives, poly[styrene‐co‐(4‐vinylbenzyltriazolylmethylmethylthymine)] (PS‐co‐PVBT). The presence of the thymine units on the side chains of the PS copolymers allows specific intermolecular association through self‐complementary T–T interactions. In addition, the thermal and dynamic rheological properties of PS‐co‐PVBT increase significantly when it is blended with melamine (M) because of the strong, complementary, multiple hydrogen‐bonding interactions that occur between the T units and this low‐molecular‐weight compound (M).     

Tardive gait

Tardive dyskinesia (TD) is a hyperkinetic movement disorder induced by dopamine receptor blocking drugs (DRBDs). TD typically presents with stereotypy or dystonia, but may also cause akathisia, myoclonus, or tremor. However, no detailed reports of gait abnormalities have been documented. We report three patients exposed to DRBDs who developed "tardive gait" and conclude that gait dysfunction may be part of the TD spectrum.     

Bioisosteric replacement of the pyrazole 5-aryl moiety of N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A). A novel series of alkynylthiophenes as potent and selective cannabinoid-1 receptor antagonists

Replacing the conventional pyrazole 5-aryl substituent of 1 (SR141716A) with the 2-thienyl moiety appended with an appropriate alkynyl unit, a novel class of 5-(5-alkynyl-2-thienyl)pyrazole derivatives, behaving as highly potent CB1 receptor antagonists with good CB1/2 selectivity, was discovered, many of which, as typified by compound 18, showed significant weight reduction in diet-induced obese mouse model, thus pharmacologically validating that the bioisosteric replacement described above is viable. Also encouraging was the finding that a subtle structural modification of the newly developed series could result in a distinct difference in the intrinsic property, as demonstrated by compounds 12 (NA) and its methylated structural isomers 15 (PA) and 18 (IA). Moreover, current structure-activity relationship studies revealed that around the pyrazole 5-position of 1, a deep and flat crevice surrounded by a sequence of hydrophobic/aromatic residues as indicated by the CB1-receptor homology model might exist in the binding site.     

The role of surgery in the management of unusual complications of transcatheter arterial embolization for hepatocellular carcinoma

Transcatheter arterial embolization (TAE) is accepted to be an effective treatment in both resectable and nonresectable hepatoma, which is very prevalent in Taiwan. Two hundred and twenty-five embolizations of TAE were performed in 137 patients in a 3-year period. Postembolization syndrome developed in the majority of patients. We analyzed these patients to study the nature and incidence of unusual complications and the surgical role in their managment. In our series, unusual complications, which were rarely reported in the literature, included 13 cases (5.8%) of gastroduodenal bleeding, 2 cases (0.9%) of duodenal perforation, 9 cases (4.0%) of acute pancreatitis with 1 case of gangrenous change, 24 cases (10.7%) of gallbladder infarction with 1 case of perforation, 4 cases (1.8%) of delayed formation of gallstones, 3 cases (1.3%) of hyperuricemia, and 2 cases (0.9%) of hepatoma rupture. Ischemic necrosis of the organs may be attributed to the inadvertent blockade of the gastroduodenal artery, gastric artery, cystic artery, and important collaterals. Inadequate superselectivity, the size of the tumor, regurgitation of embolus, anatomical variations, injury of vessel intima, or pseudoaneurysm formation resulting from previous embolization attempts made the avoidance of complications difficult with this technique. Most of the unusual complications could be managed by conservative treatment, but urgent operation was indicated in the cases of organ perforation. Elective operation was also needed for the delayed formation of gallstones with prominent symptoms. Awareness of the occurrence of these untoward sequelae makes us more careful in the evaluation and long-term follow-up of patients following TAE. Surgical intervention plays a selective but important role in the management of these unusual complications.

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Resumen La embolización arterial por cateterismo (EAC) es aceptada como tratamiento efectivo tanto en los hepatomas resecables como en los no resecables, tumores de alta incidencia en Taiwan. Doscientos veinticinco embolizaciones por EAC fueron realizadas en 137 pacientes en un período de 3 años; el síndrome de postembolización se desarrolló en la mayoría de los pacientes. Hemos analizado estos pacientes para estudiar la naturaleza y la incidencia de las complicaciones poco usuales y el papel de la cirugía en su manejo. Las complicaciones poco usuales observadas en nuestra serie, las cuales son raramente informadas en la literatura, incluyen 13 casos (5.8%) de hemorragia gastroduodenal, 2 casos (0.9%) de perforación duodenal, 9 casos (4.0%) de pancreatitis aguda con 1 caso de necrosis gangrenosa, 24 casos (10.7%) de infarto de la vesícula biliar con 1 caso de perforación, 4 casos (1.8%) de formación tardía de cálculos, 3 casos (1.3%) de hiperuricemia, y 2 casos (0.9%) de ruptura del hepatoma. La necrosis isquémica de los órganos puede ser atribuida a la oclusión inadvertida de la arteria gastroduodenal, la arteria gástrica, la arteria cística, y colaterales importantes. Superselectividad inadecuada, tamaño del tumor, regurgitación del émbolo, variaciones anatómicas, lesión de la íntima de la pared vascular, o formación de pseudoaneurismas como consecuencia de intentos previos de embolización hicieron difícil evitar las complicaciones con esta técnica. La mayoría de estas complicaciones poco usuales pudieron ser manejadas con tratamiento conservador, pero la operación de urgencia fue necesaria en casos de perforación de un órgano. La operación electiva también fue necesaria en los casos con formación tardía de cálculos biliares y síntomas prominentes. La toma de conciencia sobre la posibilidad de este tipo de secuelas nos ha hecho aún más cuidadosos en la evaluación y el seguimiento a largo plazo de los pacientes sometidos a EAC. La intervención quirúrgica juega un papel selectivo pero importante en el manejo de estas complicaciones poco usuales.

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Résumé L'embolisation par cathétérisme artériel occupe à Taiwan une place fiable dans le traitement de l'hépatome opérable ou de l'hépatome inopérable. Au cours d'une période de 3 ans 225 embolisations intra-artérielle ont été pratiquées chez 137 malades. Dans la majorité des cas l'embolisation a entrainé des phénomènes secondaires anormaux. Les auteurs font état de complications inhabituelles qui ont été rarement relatées dans la littérature: 13 cas (5.8%) d'hémorragie gastro-duodénale, 2 cas (0.9%) de perforation duodénale, 9 cas (4.0%) de pancréatite aigue dont une avec altérations gangréneuses, 24 cas (10.7%) d'infarcissement de la vésicule dont un avec perforation, 4 cas (1.8%) de formation retardée de calculs vésiculaires, 3 cas (1.3%) d'hyperuricémie, 2 cas (0.9%) de rupture de l'hématome. La nécrose ischémique des organes peut être attribuée à l'obstruction imprévue de l'artère gastro-duodénale, de l'artère gastrique, de l'artère cystique, et d'importantes collatérales. De multiples facteurs peuvent être invoqués pour expliquer les complications indésirables de l'embolisation: cathétérisme hypersélectif inadéquat, volume de la tumeur, régurgitation de l'embolus, blessure de l'intima artérielle, formation pseudoanévrysmale résultant de tentatives antérieures de cathétérisme artériel. La majorité d'entre elles peuvent être traitées médicalement mais l'intervention d'urgence s'impose quand une perforation viscérale est en cause. Il convient également de procéder à la cholécystectomie lorsque la lithiase vésiculaire entraîne des troubles importants. Connaître l'existence possible de ces accidents fâcheux doit rendre circonspect dans l'évaluation exacte de la valeur et le suivi à long terme de l'embolisation. De toute façon l'intervention chirurgicale est indispensable pour traiter certaines complications de l'embolisation.

     

Trio‐whole‐exome sequencing and preimplantation genetic diagnosis for unexplained recurrent fetal malformations

Whole‐exome sequencing (WES) is widely used to detect genetic mutations that cause Mendelian diseases, and has been successfully applied in combination with preimplantation genetic diagnosis (PGD) to avoid the transmission of genetic defects. We investigated 40 nonconsanguineous families with unexplained, recurrent fetal malformations (two or more malformed fetuses) from May 2016 to December 2018. Using Trio‐WES, we identified 32 disease‐associated variants in 40 families (80% positive rate), which were subsequently verified. Known Mendelian diseases were identified in 12 families (30%), highly suspected Mendelian diseases in 12 families (30%), variants with uncertain significance in 8 families (20%), and no noticeable variants for 8 families (20%). Further analysis showed variants in 22 genes may cause fetal malformations. Four gene variants were detected in fetuses for the first time, which expanded the spectrum of the disease phenotype. Two novel candidate genes may be related to fetal malformations. Of 26 couples receiving PGD on disease‐associated genes, 3 healthy newborns were delivered, and 4 couples are undergoing pregnancies. We reported the fetal data and developed an optimized genetic testing strategy. Our finding strongly suggests the presence of single gene Mendelian disorders in 60% of those families, and PGD services for couples to have healthy babies.     

Childhood Sexual Abuse and HIV-Related Risks Among Men Who Have Sex with Men in Washington,DC

Childhood sexual abuse (CSA) has been reported to be disproportionately higher among men who have sex with men (MSM) than among heterosexual men; it has also been found to be significantly positively associated with HIV status and HIV risk factors, including unprotected anal intercourse. The purpose of this study was to assess the correlates of CSA in a sample of community-recruited MSM, investigate race as a potential effect modifier, and describe the independent association between CSA and HIV infection in Washington, DC. A total of 500 MSM were recruited by venue-based sampling in 2008 as part of the National HIV Behavioral Surveillance. More than one-half of MSM identified as White, while one-third identified as Black. CSA was reported by 17.5 % of the 451 MSM, with the first instance of abuse occurring at a median age of 8.3 (interquartile range = 5.0, 11.0). In multivariable analysis, HIV-positive men were significantly more likely to report a history of CSA compared to HIV-negative men after adjusting for intimate partner violence in the last 12 months, having been arrested in the last 12 months, and depressive symptoms. HIV-positive MSM had more than four times the odds of reporting CSA after controlling for other correlates (aOR = 4.19; 95 % CI 2.26, 7.75). Despite hypothesizing that race modified the effect of CSA on HIV infection we found this was not the case in this sample. More research is needed to investigate the potential pathway between a history of CSA and HIV infection, and how this contributes to driving the HIV epidemic among MSM in Washington, DC.     

Nosocomial postoperative endophthalmitis: a 14-year review

Background The objective of this study was to evaluate the incidence, predisposing surgery, management and final visual outcome of postoperative endophthalmitis over a 14-year period at one institute.Methods This retrospective study reviewed all intraocular operations performed between 1 January 1991 and 31 August 2004 at Chang Gung Memorial Hospital, Kaohsiung Medical Center, to determine the incidence of nosocomial postoperative endophthalmitis and the characteristics of patients who developed this condition.Results The overall incidence of postoperative endophthalmitis after intraocular surgery was 0.19% (56 out of 30,219). Postoperative endophthalmitis developed in 56 eyes in 56 patients during the study period. The condition developed after cataract surgery in 46 eyes, after penetrating keratoplasty in 6 eyes, after filtering surgery in 2 eyes, after secondary intraocular lens implant in 1 eye, and after vitrectomy in 1 eye. Postoperative endophthalmitis was culture-positive in 31 cases (55%). The most frequent organism isolated was coagulase-negative Staphylococcus. Factors associated with better visual acuity outcomes included low virulence of isolated pathogen, initial visual acuity of counting fingers or better, and history of cataract surgery compared with other intraocular surgery.Conclusion The overall incidence of endophthalmitis after intraocular surgery was 0.19%. The results of this 14-year review from a local medical center may serve as a source of comparison for other centers and future studies.No proprietary interests     

二至丸药理作用研究进展

二至丸由女贞子、墨旱莲两味药材组成,具有补益肝肾、滋阴止血的功效,在妇科疾病、肾病、肝病等领域均有广泛的临床应用基础。现代药理研究发现二至丸在保肝补肾、改善骨质疏松、围绝经期综合征、免疫调节、抗衰老、改善神经系统疾病等方面具有广泛的药理活性,并对二至丸保护肝脏、抗骨质疏松、抗衰老的作用机制与潜在通路开展了研究。对二至丸的药理作用研究进展进行综述,为进一步利用现代药理学手段阐明二至丸治疗肝肾阴虚证的机制、挖掘中药经典方“多成分、多靶点、多通路”的作用特点以及指导二至丸临床应用提供参考。