Secretory immunoglobulin deposits in renal glomeruli of children with extrahepatic biliary atresia: studies in a human counterpart of experimental ligation of the bile ducts.
Experimental ligation of the biliary tract often results in glomerular deposits of polymeric IgA commonly associated with secretory component. These studies offer evidence that, in animals, hepatobiliary transport of polymeric IgA, which is of mucosal origin, is crucial for its clearance from the serum. We studied a human counterpart of bile duct ligation--extrahepatic biliary atresia--for the presence of secretory or polymeric immunoglobulins in renal glomeruli. Kidney was available at autopsy as paraffin or frozen blocks from 24 patients with biliary atresia and age-matched controls (5 weeks to 5 years old). Several of the patients had undergone portoenterostomy (Kasai procedure) or liver transplantation. Immunohistologic studies showed glomerular (often mesangial) deposits of IgA in 10 of 24 and IgM in 16 of 24 specimens. The differences with controls were highly significant for IgA but not for IgM. In frozen sections, secretory component was positive in glomeruli in seven of 12 specimens. In vitro glomerular binding of purified secretory component to glomeruli was shown in four of 12 samples, including three with IgM only. This last observation suggests that IgM in some of these patients was polymeric and thus derived from a mucosal source. Our study shows that in humans with biliary atresia, secretory IgA, polymeric IgA, and possibly polymeric IgM are deposited in glomeruli. The study confirms the occurrence of renal immunopathologic findings in liver disease and supports the existence of an active hepatobiliary immunosecretory transport mechanism even at the early age of these patients.


Arthroscopic Stabilization of Unstable Os Subfibulare.
Os subfibulare is an ossicle at the tip of the lateral malleolus. The ossicle is sometimes symptomatic and presents with local pain or lateral ankle instability. The purpose of this Technical Note is to describe the details of arthroscopic stabilization of the os subfibulare. It is indicated for symptomatic mechanical lateral ankle instability resulting from an unstable os subfibulare. The technique has the advantages of minimally invasive surgery, evaluation and treatment of concomitant ankle pathology, and preservation of integrity of the anterior talofibular ligament.


Analysis of multimorbidity networks associated with different factors in Northeast China: a cross-sectional analysis.
This study aimed to identify and study the associations and co-occurrence of multimorbidity, and assessed the associations of diseases with sex, age and hospitalisation duration. Cross-sectional. 15 general hospitals in Jilin Province, China. A total of 431 295 inpatients were enrolled through a cross-sectional study in Jilin Province, China. The complex relationships of multimorbidity were presented as weighted networks. The distributions of the numbers of diseases differed significantly by sex, age and hospitalisation duration (p<0.001). Cerebrovascular diseases (CD), hypertensive diseases (HyD), ischaemic heart diseases (IHD) and other forms of heart disease (OFHD) showed the highest weights in the multimorbidity networks. The connections between different sexes or hospitalisation duration and diseases were similar, while those between different age groups and diseases were different. CD, HyD, IHD and OFHD were the central points of disease clusters and directly or indirectly related to other diseases or factors. Thus, effective interventions for these diseases should be adopted. Furthermore, different intervention strategies should be developed according to multimorbidity patterns in different age groups.


Beating heart mitral valve replacement in a patient with a previous Bentall operation.
Today, mitral valve replacement is performed under cardioplegic arrest with cross-clamping of the ascending aorta. In the case reported here, mitral valve replacement was performed with an on-pump beating heart technique without cross-clamping the aorta because of diffuse adhesion around the tube graft. A 36-year-old man had undergone a Bentall operation (aortic root replacement+coronary reimplantation) via median sternotomy because of type I aortic dissection 4 years previously in our cardiac center. He was admitted to the hospital complaining of palpitation and dyspnea on mild exertion. Transthoracic echocardiography study revealed third-degree mitral insufficiency. Mitral valve replacement was carried out through re-median sternotomy with an on-pump beating heart technique without crossclamping the aorta. On-pump beating heart mitral valve replacement without a cross-clamp offers a safe approach when excessive dissection is required to place a crossclamp on the ascending aorta.


Uncertainty analysis and sensitivity of scapulothoracic joint angles to kinematic model parameters.
The purposes of this study were to determine the influence of kinematic model parameter variability on scapulothoracic angle estimates, and to define which parameters of the kinematic model have the largest effect on scapulothoracic angle estimates. Nominal subject-specific kinematic models of nine participants were implemented. Fifteen parameters of the nominal models relative to the clavicle length, ellipsoid, sternoclavicular and acromioclavicular joint centers, and contact point location were altered from - 1 to 1 cm. Then, scapulothoracic angles were computed during four movements using multibody kinematic optimizations for nominal and altered models. The percentage of scapulothoracic angle variance explained by each parameter of the kinematic model was computed using Effective Algorithm for Computing Global Sensitivity Indices. When altering simultaneously the 15 parameters of the kinematic model, scapulothoracic angles varied up to 50°. For all movements and degrees of freedom, the clavicle length significantly explained the largest part of scapulothoracic angle variance (up to 25%, p < 0.01). In conclusion, kinematic model parameters need to be estimated accurately to avoid any bias in scapulothoracic angle estimates especially in a clinical context. The present sensitivity analysis may also be used as a benchmark for future works focusing on improving shoulder kinematic models. The curves represent mean scapulothoracic angles computed with the nominal model and their variability when kinematic model parameters are altered. The colormap graphs represent the percentage of scapulothoracic angle variance explained by each parameter of the kinematic model.


Evaluation of the potentials of humic acid removal in water by gas phase surface discharge plasma.
Degradation of humic acid (HA), a predominant type of natural organic matter in ground water and surface waters, was conducted using a gas phase surface discharge plasma system. HA standard and two surface waters (Wetland, and Weihe River) were selected as the targets. The experimental results showed that about 90.9% of standard HA was smoothly removed within 40 min's discharge plasma treatment at discharge voltage 23.0 kV, and the removal process fitted the first-order kinetic model. Roles of some active species in HA removal were studied by evaluating the effects of solution pH and OH radical scavenger; and the results presented that O3 and OH radical played significant roles in HA removal. Scanning electron microscope (SEM) and FTIR analysis showed that HA surface topography and molecular structure were changed during discharge plasma process. The mineralization of HA was analyzed by UV-Vis spectrum, dissolved organic carbon (DOC), specific UV absorbance (SUVA), UV absorption ratios, and excitation-emission matrix (EEM) fluorescence. The formation of disinfection by-products during HA sample chlorination was also identified, and CHCl3 was detected as the main disinfection by-product, but discharge plasma treatment could suppress its formation to a certain extent. In addition, approximately 82.3% and 67.9% of UV254 were removed for the Weihe River water and the Wetland water after 40 min of discharge plasma treatment.


Estimating extra length of stay and risk factors of mortality attributable to healthcare-associated infection at a Chinese university hospital: a multi-state model.
The current evidence of extra length of stay (LOS) attributable to healthcare-associated infection (HCAI) scarcely takes time-dependent bias into consideration. Plus, limited evidences were from developing countries. We aim to estimate the extra LOS and risk factors of mortality attributable to HCAI for inpatients. Multi-state model (MSM) was adopted to estimate the extra LOS attributable to HCAI of each type and subgroup. COX regression model was used to examine the risk of mortality. A total of 51,691 inpatients were included and 1709 (3.31%) among them developed HCAI. Lower respiratory tract infection and Acinetobacter baumannii were the most prevalent HCAI and causative pathogen in surveyed institute. Generally, the expected extra LOS attributable to HCAI was 2.56 days (95% confidence interval: 2.54-2.61). Patients below 65 had extra LOS attributable to HCAI longer about 2 days than those above. The extra LOS attributable to HCAI of male patients was 1.33 days longer than female. Meanwhile, age above 65 years old and HCAI were the risk factors of mortality for inpatients. HCAI contributes to an increase in extra LOS of inpatients in China. The effect of HCAI on extra LOS is different among subgroups, with the age below 65, male and medicine department more sensitive.


Ring currents as probes of the aromaticity of inorganic monocycles : P5-, As5-, S2N2, S3N3-, S4N3+, S4N42+, S5N5+, S42+ and Se42+.
Current-density maps were calculated by the ipsocentric CTOCD-DZ/6-311G** (CTOCD-DZ=continuous transformation of origin of current density-diamagnetic zero) approach for three sets of inorganic monocycles: S(4) (2+), Se(4) (2+), S(2)N(2), P(5) (-) and As(5) (-) with 6 pi electrons; S(3)N(3) (-), S(4)N(3) (+) and S(4)N(4) (2+) with 10 pi electrons; and S(5)N(5) (+) with 14 pi electrons. Ipsocentric orbital analysis was used to partition the currents into contributions from small groups of active electrons and to interpret the contributions in terms of symmetry- and energy-based selection rules. All nine systems were found to support diatropic pi currents, reinforced by sigma circulations in P(5) (-), As(5) (-), S(3)N(3) (-), S(4)N(3) (+), S(4)N(4) (2+) and S(5)N(5) (+), but opposed by them in S(4) (2+), Se(4) (2+) and S(2)N(2). The opposition of pi and sigma effects in the four-membered rings is compatible with height profiles of calculated NICS (nucleus-independent chemical shifts).


Direct measurement of middle ear pressure through the eustachian tube.
We report a method for measuring middle ear pressure through the eustachian tube. We used a 1-mm-diameter micro-tip catheter pressure transducer (Mikro-tip) and inserted this into the tympanic cavity through the eustachian tube. In preliminary studies, we measured four normal ears, two ears with tubal dysfunction, one ear with a dry perforation and 13 ears with otitis media with effusion (OME). Among those ears with OME, three showed negative middle ear pressure, three slight positive pressure and one normal pressure. These findings suggest that our transtubal method is reliable and useful for measuring middle ear pressure.


Development of a survival animal model for subglottic stenosis.
To develop a reproducible survival animal model for subglottic stenosis. Prospective study. We evaluated five methods of inducing airway injury in 30 New Zealand white rabbits to produce a subglottic stenosis model. Experimental groups comprised: group 1 (n = 5), which underwent 4-hour intubation; group 2 (n = 5), which underwent induced subglottic injury with a nylon brush; group 3 (n = 10), which underwent subglottic injury with a nylon brush, followed by 4-hour intubation; group 4 (n = 5), which underwent subglottic injury with Bugbee cautery in 50% of the subglottic circumference, followed by 4-hour intubation; and group 5 (n = 5), which underwent subglottic injury with Bugbee cautery in 75% of the subglottic circumference, followed by 4-hour intubation. Five animals were used as controls. Endoscopy of the airway and sacrifice of animals were planned at an interval of 14 days postinjury. Histologic measurements were analyzed. No animals in groups 1 or 2 developed stenosis. In group 3, 50% of animals developed symptomatic grade 3 subglottic and tracheal stenosis, necessitating early endoscopy and sacrifice in three animals. Four animals in group 4 developed grade 1 subglottic stenosis, and four in group 5 developed grade 2 subglottic stenosis. Histologic measurements of lumen areas within each of these two groups were similar; all animals survived the follow-up period. We successfully developed a reproducible survival model for induced subglottic stenosis using a combination of cautery-induced subglottic injury followed by 4-hour intubation. This model lays the foundation for future studies that evaluate endoscopic interventions for the management of subglottic stenosis. NA Laryngoscope, 129:989-994, 2019.


New research in breast reconstruction: adipose tissue engineering.
In the human species, a major function of the breast is aesthetic. The soft-tissue volume within the breast displaces the overlying skin to create the protuberant contour of the female thorax, that is solidly associated with, and to some extent, definitive of, femininity in modern culture. Adipose tissue is the major contributor to the volume of the breast.


Reactivation of a silenced minimal Mutator transposable element system following low-energy nitrogen ion implantation in maize.
In maize, Mutator transposable elements are either active or silenced within the genome. In response to environmental stress, silenced Mutator elements could be reactivated, leading to changes in genome structure and gene function. However, there is no direct experimental evidence linking environmental stress and Mutator transposon reactivation. Using a maize line that contains a single inactive MuDR and a lone nonautonomous Mutator element, a Mu1 insertion in the recessive reporter allele a1-mum2 in an inactive Mutator background, we directly assessed Mutator reactivation following low-energy nitrogen ion implantation. We observed that N(+) implantation decreased cytosine methylation in MuDR terminal inverted repeats and increased expression of mudrA and mudrB. Both changes were associated with increased transpositional activity of MuDR through reactivation of the inactive minimal Mutator transposable element system. This study provides direct evidence linking environmental stress agents and Mutator transposon mobilization in maize. In addition, the observed changes to DNA methylation suggest a new mechanism for mutations by low-energy ion implantation.


Role of computerised tomography in management of intra-articular fractures of the os calcis.
This study aimed to look at the role played by the CT scan in decision making in the management of intra-articular fractures of the calcaneum. Twenty-four patients with intra-articular fractures of the calcaneum were included. Their initial radiographs and CT films were blinded and assessed by three independent observers. Based on this they were selected for operative or non-operative management. The actual management was also recorded. The data were then subjected to statistical analysis to look at the association between the decision from radiograph, that from the CT scan and the actual management undertaken. Non-parametric tests for related samples were performed to look at the association between the actual management and the decisions made by assessing the radiographs and the CT scans. For all three observers, there was no significant difference between the actual management and decisions made by assessing the plain radiographs or the CT scan. There was also no significant difference between the radiograph-based and the CT-based decisions. However, the Cochran Q test showed that there was significant variation among the three observers for the CT-based assessment. Our results, show that the CT scan should only be done when a definite decision is made to operate on a patient, based on plain radiographs. Calcaneal fractures which are selected for non-operative management, based on X rays, should not have a CT scan as a routine as it provides no valuable additional information affecting the management decision.


Conversion of RNA to DNA in mammals: Alu-like elements and pseudogenes.
Striking similarities between a subclass of mammalian pseudogenes and the Alu family of short repetitive DNA sequences which are dispersed throughout the mammalian genome, suggest that both are created by integration into the genome of DNA copies of RNA transcripts.


Enhanced hybridoma production by electrofusion in strongly hypo-osmolar solutions.
Electrofusion of mammalian cells in strongly hypo-osmolar media containing sorbitol, small amounts of divalent cations and albumin resulted in high yields of hybrids. The number of viable hybrids was higher than any value for chemically- or electrically-mediated fusion reported in the literature. Optimum clone numbers were obtained for fusion of osmotically-stable subclones of murine myeloma cells with DNP-Hy-stimulated lymphocytes provided that the osmolarity of the fusion medium was as low as 75 mosmol/l. Similar results were obtained for fusion of osmotically stable subclones of myeloma cells with the murine hybridoma cell line G8. Due to the dramatic increase in volume the field strength of the breakdown pulse (leading to fusion of the dielectrophoretically aligned cells) has to be reduced, as predicted by theory. The efficacy of hypo-osmolar electrofusion allowed the use of very few cells (about 10(5) lymphocytes or G8 cells per fusion chamber). This figure is considerably smaller than that reported in the literature for iso-osmolar electrofusion. It is significant that, in contrast to iso-osmolar conditions, the fusion yield in hypo-osmolar electrofusion was reproducible over long periods of time and less dependent of variations between cultures. At suspension densities of about 10(6) cells per fusion chamber (normally used in iso-osmolar electrofusion) hypo-osmolar electrofusion of homogeneous cell suspensions resulted in the formation of many giant cells when the appropriate field conditions were applied. Similar high or, at some field strengths, even higher numbers of clones at low cell suspension density were obtained when G8 and myeloma cells were first exposed during the washing procedure to strongly hypo-osmolar media, but then transferred to iso-osmolar solutions for electrofusion. Similar experiments with lymphocytes and myeloma cells failed because of destruction of many lymphocytes by the two osmotic shock steps in rapid succession. Volume distribution measurements of G8 and myeloma cells showed that after re-incubation of the osmotically pre-stressed cells the original volume distribution is largely, but not completely re-established. This and other results indicate that osmotic pressure gradients and associated tensions in the membrane do not play a primary role in the initiation of the electrofusion process. The experiments suggest that due to the osmotic (pre-) stress the membrane permeability is slightly and uniformly increased presumably due to the dissolution of membrane- and cell-skeleton proteins. Obviously, this facilitates electrofusion in hypo-osmolar or subsequently in iso-osmolar solutions.


Effectiveness of training stop-smoking advisers to deliver cessation support to the UK national proposed standard versus usual care in Malaysia: a two-arm cluster-randomized controlled trial.
To assess the effectiveness of training stop smoking services providers in Malaysia to deliver support for smoking cessation based on the UK National Centre for Smoking Cessation and Training (NCSCT) standard treatment programme compared with usual care. Two-arm cluster-randomized controlled effectiveness trial across 19 sites with follow-up at 4-week, 3-month, and 6-month. Stop smoking services operating in public hospitals in Malaysia. Five hundred and two smokers [mean ± standard deviation (SD), age 45.6 (13.4) years; 97.4% male] attending stop smoking services in hospital settings in Malaysia: 330 in 10 hospitals in the intervention condition and 172 in nine hospitals in the control condition. The intervention consisted of training stop-smoking practitioners to deliver support and follow-up according to the NCSCT Standard Treatment Programme. The comparator was usual care (brief support and follow-up). The primary outcome was continuous tobacco smoking abstinence up to 6 months in smokers who received smoking cessation treatment, verified by expired-air carbon monoxide (CO) concentration. Secondary outcomes were continuous CO-verified tobacco smoking abstinence up to 4 weeks and 3 months. Follow-up rates at 4 weeks, 3 months and 6 months were 80.0, 70.6 and 53.3%, respectively, in the intervention group and 48.8, 30.8 and 23.3%, respectively, in the control group. At 6-month follow-up, 93 participants in the intervention group and 19 participants in the control group were abstinent from smoking, representing 28.2 versus 11.0% in an intention-to-treat (ITT) analysis assuming that participants with missing data had resumed smoking, and 52.8 versus 47.5% in a follow-up-only (FUO) analysis. Unadjusted odds ratios (accounting for clustering) were 5.04, (95% confidence interval (CI) = 1.22-20.77, P = 0.025) and 1.70, (95% CI = 0.25-11.53, P = 0.589) in the ITT and FUO analyses, respectively. Abstinence rates at 4 week and 3 month follow-ups were significantly higher in the intervention versus control group in the ITT but not the FUO analysis. On an intention-to-treat analysis with missing-equals-smoking imputation, training Malaysian stop smoking service providers in the UK National Centre for Smoking Cessation and Training standard treatment programme appeared to increase 6 month continuous abstinence rates in smokers seeking help with stopping compared with usual care. However, the effect may have been due to increasing follow-up rates.


Multiple indicators of violence against female sex workers and its associated factors in Ghana: Evidence from the 2015 integrated bio-behavioral surveillance survey cross-sectional study.
Violence against female sex workers (FSWs) is a widespread phenomenon, especially in African nations like Ghana where sex work is outlawed primarily because of the pervasive worldview that sex work is a contravention of morality. Violence against FSWs deters them from accessing critical health services and heightens their risk of STIs including HIV infection. The study examined the prevalence and the associated factors of multiple indicators of violence against FSWs. The study utilized a cross-sectional secondary data from the 2015 Integrated Bio-Behavioral Surveillance Survey conducted among FSWs and their nonpaying partners by Ghana AIDS Commission. We analysed data on a total of 4279 participants. Bivariate, and multivariable logistic regression analyses were utilized to identify factors associated with physical and sexual violence against FSWs. Data were analysed using Stata version 15. Of the 4279 FSWs, 433 (10%) and 1059 (25%) suffered physical and sexual violence, respectively. The predictors of physical violence are being a seater (adjusted odds ratio [aOR] = 0.53, 95% confidence interval [CI]: 0.36-0.74), aged ≥40 (aOR = 0.23, 95% CI: 0.08-0.64), nonuse of drugs (aOR = 0.56, 95% CI: 0.44-0.70), not using alcohol before sex (aOR = 0.69, 95% CI: 0.56-0.86) and petty business (aOR = 1.39, 95% CI: 1.05-1.82). Sexual violence was predicted by those aged 31-40 (aOR = 0.68, 95% CI: 0.49-0.94) and age ≥40 (aOR = 0.38, 95% CI: 0.22-0.66), currently married (aOR = 0.42, 95% CI: 0.27-0.67), having no living children (aOR = 0.69, 95% CI: 0.51-0.94), nonuse of drugs (aOR = 0.80, 95% CI: 0.68-0.94), and not using alcohol before sex (aOR = 0.74, 95% CI: 0.63-0.86). Region was associated with both physical and sexual violence. Both physical and sexual violence had negative consequences on consistency of condom use and condom failure among FSWs. Physical and sexual violence against FSWs is pervasive, and a critical public health issue in Ghana. The identified associated factors could be considered as part of an overall strategy aimed at addressing the menace.


A case of a resectable single hepatic epithelioid hemangioendothelioma with characteristic imaging by ADC map.
A 47-year-old woman with a single-nodule hepatic tumor was referred to our hospital. She had no symptoms. The tumor was located at the surface of the right lobe of the liver; it showed peripheral low signal intensity on a magnetic resonance imaging apparent diffusion coefficient (ADC) map, and an influx of blood flow into the peripheral area of the tumor at the early vascular phase on perflubutane microbubble (Sonazoid(®)) contrast-enhanced (CE) ultrasonography. Since we suspected a malignant tumor, the patient underwent surgical resection. The hepatic tumor was resected curatively. Pathological examination revealed that the tumor was composed of epithelioid cells with an epithelioid structure and/or cord-like structure. Immunohistochemical staining was positive for cluster of differentiation 34 and factor VIII-related antigen. Based on the above, a final diagnosis of hepatic epithelioid hemangioendothelioma (EHE) was made. Hepatic EHE is a rare hepatic tumor: only a few cases of hepatic EHE with curative resection have been reported. We were unable to reach a diagnosis of hepatic EHE by imaging studies; however, an ADC map was useful in showing the malignant potential of the tumor, and CE ultrasonography was useful in revealing the peripheral blood flow of the tumor. When an unusual hepatic mass is encountered, hepatic EHE should be kept in mind, and the mass should be inspected with more than one imaging modality, including an ADC map, in the process of differential diagnosis.


Inhibition of airway smooth muscle contraction and proliferation by LIM kinase inhibitor, LIMKi3.
Current medical treatment for asthma aims to inhibit airway smooth muscle (ASM) contraction and proliferation, however, the efficacy of available treatment options is unsatisfactory. Therefore, we explored the effect of LIM domain kinase (LIMK) inhibitor - LIMKi3, on ASM to improve the understanding of ASM contraction and proliferation mechanisms, and to investigate new therapeutic targets. Asthma model was induced in rats by intraperitoneal injection of ovalbumin. Using phospho-specific antibodies, we examined LIMK, phosphorylated LIMK, cofilin and phosphorylated cofilin. ASM contraction was studied in organ bath experiments. ASM cells proliferation was studied with cell counting kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays. Immunofluorescence indicated that LIMKs are expressed in ASM tissues. Western blot revealed that LIMK1 and phospho-cofilin were significantly elevated in asthma ASM tissues. The LIMK inhibitor, LIMKi3 (1 μM) could reduce cofilin phosphorylation and therefore inhibit contraction of ASM tissues, and induce actin filament breakdown as well as cell proliferation reduction in cultured human ASM cells. ASM contraction and proliferation in asthma may underlie the effects of LIMKs. Small molecule LIMK inhibitor, LIMKi3, might be a potential therapeutic strategy for asthma.


Interstimulus interval (ISI) discrimination of the conditioned eyeblink response in a rodent model of autism.
Rats exposed to valproic acid (VPA) on gestational day 12 (GD12) have been advanced as a rodent model of autism [Arndt TL, Stodgell, Rodier PM. The teratology of autism. Int J Dev Neurosci 2005;23: 189-99.]. These rats show cerebellar anomalies and alterations in eyeblink conditioning that are associated with autism. Autistic humans and VPA-exposed rats show normal responses to conditioned and unconditioned stimuli, but they show marked differences from comparison groups in acquisition, magnitude, and timing of the conditioned response (CR). This study examined VPA-induced eyeblink CR timing differences by training rats on an interstimulus interval (ISI) discrimination task, in which two distinct conditioned stimuli (CS; tone and light) are paired with the same unconditioned stimulus (US; periocular shock) at two distinct CS-US intervals. Previous findings suggest that this task would produce abnormally large and prematurely timed CRs for VPA-exposed rats relative to controls. Adult male Long-Evans rats that were exposed to either VPA or saline on GD 12.5 were trained on an ISI discrimination task [Brown KL, Pagani JH, Stanton ME. The ontogeny of interstimulus interval (ISI) discrimination of the conditioned eyeblink response in rats. Behav Neurosci 2006;120: 1057-70.]. In support of earlier findings, we observed early acquisition and enhanced magnitude of the CR in VPA rats compared with controls on long CS trials. VPA rats also showed prematurely timed CRs to long- CS trials, but not to short- CS trials. The ISI discrimination procedure used in the current study reveals differential timed responses in this animal model of autism not previously seen.


Enhanced antibiotic activity of ampicillin conjugated to gold nanoparticles on PEGylated rosette nanotubes.
This work presents the preparation of a nanocomposite of ampicillin-conjugated gold nanoparticles (AuNPs) and self-assembled rosette nanotubes (RNTs), and evaluates its antibacterial properties against two strains of drug-resistant bacteria (Staphylococcus aureus [S. aureus], methicillin-resistant S. aureus [MRSA]). Small, nearly monodisperse AuNPs (1.43±0.5 nm in diameter) nucleated on the surface of polyethylene glycol-functionalized RNTs in a one-pot reaction. Upon conjugation with ampicillin, their diameter increased to 1.86±0.32 nm. The antibacterial activity of the nanocomposite against S. aureus and MRSA was tested using different concentrations of ampicillin. The cytocompatibility of the nanocomposite was also tested against human dermal fibroblasts. Based on bacterial inhibition studies, the nanocomposite demonstrated enhanced antibiotic activity against both bacterial strains. The minimum inhibitory concentration (MIC) of the nanocomposite against S. aureus was found to be 0.58 μg/mL, which was 18% lower than ampicillin alone. The nanocomposite also exhibited a 20 hrs MIC of 4 μg/mL against MRSA, approximately 10-20 times lower than previously reported values for ampicillin alone. In addition, at concentrations of 4 μg/mL of ampicillin (70 μg/mL of AuNPs), the nanocomposite showed negligible cytotoxic effects. Our findings offer a new approach for the treatment of drug-resistant bacteria by potentiating inhibitory effects of existing antibiotics, and delivering them using a non-toxic formulation.


Percutaneous Radiologic Gastrostomy in Patients After Partial Gastrectomy: A Retrospective Study to Assess the Technical Feasibility of Postsurgical Remnant Stomach Access.
To evaluate the technical feasibility of percutaneous radiologic gastrostomy in patients after partial gastrectomy. This retrospective study included 15 consecutive gastrectomized patients with attempted percutaneous radiologic gastrostomy at our institution between April 2014 and March 2021. When the stomach was sufficiently insufflated to distend below the left anterior subcostal margin, percutaneous radiologic gastrostomy with gastropexy was conventionally performed by the Seldinger technique. When the stomach was still highly positioned and/or overlaid by the other organs, some adjunctive maneuvers, such as hydro-displacement, intragastric balloon support, or cephalad oblique puncture or left intercostal puncture, were employed as modified gastrostomy. Ultrasonography or x-ray or computed tomography fluoroscopy was used for imaging guidance during the gastric puncture. Adequate tube placement was defined as technical success. Technical details, clinical outcomes, and complications were reviewed. One patient underwent percutaneous radiologic jejunostomy instead of gastrostomy because safe gastric access could not be ensured. Seven patients underwent conventional gastrostomy; the other seven underwent modified gastrostomy with no gastropexy. The technical success rate was 100% (7/7) in the conventional group and 85.7% (6/7) in the modified group. The stomach was punctured under x-ray or computed tomography fluoroscopy for conventional gastrostomy. In contrast, the combination of various modalities was used for modified gastrostomy except for one failed case with unintentional transhepatic access. During a median follow-up of 108 days, no major complications occurred. The adequate combination of multimodal imaging guidance and technical modifications could secure radiological creation of gastrostomy for the postsurgical stomach. Level 4, Case Series.


Implementing high-dimensional propensity score principles to improve confounder adjustment in UK electronic health records.
Recent evidence from US claims data suggests use of high-dimensional propensity score (hd-PS) methods improve adjustment for confounding in non-randomised studies of interventions. However, it is unclear how best to apply hd-PS principles outside their original setting, given important differences between claims data and electronic health records (EHRs). We aimed to implement the hd-PS in the setting of United Kingdom (UK) EHRs. We studied the interaction between clopidogrel and proton pump inhibitors (PPIs). Whilst previous observational studies suggested an interaction (with reduced effect of clopidogrel), case-only, genetic and randomised trial approaches showed no interaction, strongly suggesting the original observational findings were subject to confounding. We derived a cohort of clopidogrel users from the UK Clinical Practice Research Datalink linked with the Myocardial Ischaemia National Audit Project. Analyses estimated the hazard ratio (HR) for myocardial infarction (MI) comparing PPI users with non-users using a Cox model adjusting for confounders. To reflect unique characteristics of UK EHRs, we varied the application of hd-PS principles including the level of grouping within coding systems and adapting the assessment of code recurrence. Results were compared with traditional analyses. Twenty-four thousand four hundred and seventy-one patients took clopidogrel, of whom 9111 were prescribed a PPI. Traditional PS approaches obtained a HR for the association between PPI use and MI of 1.17 (95% CI: 1.00-1.35). Applying hd-PS modifications resulted in estimates closer to the expected null (HR 1.00; 95% CI: 0.78-1.28). hd-PS provided improved adjustment for confounding compared with other approaches, suggesting hd-PS can be usefully applied in UK EHRs.


Neonatal rat surgery: avoiding maternal cannibalism.
A simple program of handling and care of pregnant rats before delivery makes it possible to carry out surgical procedures on newborn pups without resultant cannibalism or rejection of the operated animals by their mothers.


Bionic 3D spheroids biosensor chips for high-throughput and dynamic drug screening.
To perform the drug screening, planar cultured cell models are commonly applied to test efficacy and toxicity of drugs. However, planar cultured cells are different from the human 3D organs or tissues in vivo. To simulate the human 3D organs or tissues, 3D spheroids are developed by culturing a small aggregate of cells which reside around the extracellular matrix and interact with other cells in liquid media. Here we apply lung carcinoma cell lines to engineer the 3D lung cancer spheroid-based biosensor using the interdigitated electrodes for drug efficacy evaluation. The results show 3D spheroid had higher drug resistance than the planar cell model. The anticarcinogen inhibition on different 3D lung cancer spheroid models (A549, H1299, H460) can be quantitatively evaluated by electric impedance sensing. Besides, we delivered combination of anticarcinogens treatments to A549 spheroids which is commonly used in clinic treatment, and found the synergistic effect of cisplatin plus etoposide had higher drug response. To simultaneously test the drug efficacy and side effects on multi-organ model with circulatory system, a connected multiwell interdigitated electrode arraywas applied to culture different organoid spheroids. Overall, the organization of 3D cancer spheroids-based biosensor, which has higher predictive value for drug discovery and personalized medicine screening, is expected to be well applied in the area of pharmacy and clinical medicine.


The effect of Irisin on antioxidant system in liver.
Nonalcoholic fatty liver disease (NAFLD) is a global health problem and lead to subacute liver failure, cirrhosis and/or hepatocellular carcinoma. An increased generation of reactive oxygen species (ROS) and antioxidant depletion is found in the liver of obese patients with NAFLD. Irisin is a recently identified exercise-induced myokine. It increases total energy consumption, reduces body weight, and insulin resistance. It was shown that irisin levels were significantly lower in patients with NAFLD. The aim of the present study was to investigate the effect of irisin on prooxidant-antioxidant balance in liver. In the first phase; AML12 liver cells were divided into 4 groups: control, hydrogen peroxide (H2O2)-treated, 10nM irisin-treated and 50nM irisin-treated groups. ROS accumulation in these groups was analyzed by FACS. In the second phase; to see if there is any protective role of irisin on ROS production in the liver, AML12 liver cells were divided into 4 groups: control, H2O2 -treated, H2O2+10nM irisin-treated and H2O2+50nM-irisin treated groups. After measuring ROS accumulation again in these groups, the levels of enzymes related with prooxidant-antioxidant balance via oxidative stress in liver were measured by western blotting. In H2O2 treatment groups, ROS production was increased in AML12 liver cells, on the other hand in irisin treatment groups ROS production was slightly changed. Irisin might be a potential target for metabolic diseases like NAFLD.


Ultrastructure of lateral line organs in aneurogenic amphibian larvae (Ambystoma).
An ultrastructural study was performed to determine the ability of presumptive lateral line tissue in A. maculatum embryos to migrate and differentiate in the absence of all sensory innervation. In experimental animals, all presumptive neural tissue was surgically removed at Harrison's stage 24, leaving only the posterior portion of the post-auditory placode. At later stages, completely differentiated aneural lateral line organs were found in the midbody region of the larvae. These were morphologically similar to those of control larvae. No signs of atrophy or degeneration of the neuromasts were seen even after several weeks of nerve-free conditions.


Structural effects of the active site mutation cysteine to serine in Bacillus cereus zinc-beta-lactamase.
Beta-lactamases are involved in bacterial resistance. Members of the metallo-enzyme class are now found in many pathogenic bacteria and are becoming thus of major clinical importance. Despite the availability of Zn-beta-lactamase X-ray structures their mechanism of action is still unclear. One puzzling observation is the presence of one or two zincs in the active site. To aid in assessing the role of zinc content in beta-lactam hydrolysis, the replacement by Ser of the zinc-liganding residue Cys168 in the Zn-beta-lactamase from Bacillus cereus strain 569/H/9 was carried out: the mutant enzyme (C168S) is inactive in the mono-Zn form, but active in the di-Zn form. The structure of the mono-Zn form of the C168S mutant has been determined at 1.85 A resolution. Ser168 occupies the same position as Cys168 in the wild-type enzyme. The protein residues mostly affected by the mutation are Asp90-Arg91 and His210. A critical factor for the activity of the mono-Zn species is the distance between Asp90 and the Zn ion, which is controlled by Arg91: a slight movement of Asp90 impairs catalysis. The evolution of a large superfamily including Zn-beta-lactamases suggests that they may not all share the same mechanism.


Familial occurrence of blind-ending bifid and duplicated ureters.
Blind-ending bifid ureter in a girl with urinary tract infection, and a blind-ending duplicated ureter in her younger sister are described. The embryology of this rare anomaly is briefly reviewed.


Intravenous acetaminophen reduces the length of intubation and rescue analgesics in intensive care unit patients after cardiovascular surgery in Japan: A retrospective analysis.
After cardiovascular surgery, analgesic and sedative management in the intensive care unit (ICU) significantly affects short- and long-term outcomes of patients. This study aimed to clarify the impact of opioid reduction after acetaminophen administration on the length of intubation and rescue analgesic use after cardiovascular surgery. This was a case-control study. This study was conducted in the ICU of a cardiovascular hospital. Datasets of 556 post-cardiac surgery participants were collected; for final analyses, 266 participants were selected by propensity score matching. Equality between the intervention and comparison groups was ensured by calculating the standardized difference and difference test. The intervention group was treated with the multimodal analgesic sedation protocol. The primary outcomes were the length of intubation and use of rescue analgesics. The intervention group demonstrated a decreased total opioid consumption (460.0 vs 580.0 mcg, effect size [ES] = -0.178), opioid administration time (1,130.0 vs 2,070.0 minutes, ES = -0.306), and sedative administration time (955.0 vs 1,577.0 minutes, ES = -0.354). Moreover, the protocol resulted in decreased duration of ventilation (990.0 vs 1,057.5 minutes, ES = -0.140) and reduced need for rescue analgesics, including flurbiprofen axetil (3.5 vs 34.5 percent, ES = -0.392) and loxoprofen sodium (19.5 vs 48.1 percent, ES = -0.284). This study suggested that acetaminophen reduces opioid use and improves patient outcomes after cardiovascular surgery. Moreover, this research provides essential information for developing analgesic management strategies to reduce opioid consumption in patients after cardiovascular surgery.


Deep understanding of structure-solubility relationship for a diverse set of organic compounds using matched molecular pairs.
Aqueous solubility is an important biopharmaceutical property in drug discovery and development. Although it has been studied for decades, the impact on solubility by the substructures (or fragments) of compounds are still not fully understood and characterized. This study aims to obtain fragment-solubility relationships using matched molecular pairs, and to provide further insight and suggestions for chemists on structural modifications to improve solubility profiles of drug-like molecules. A set of 2794 compounds with measured intrinsic aqueous solubility (logS) was fragmented into rings, linkers, and R groups using a controlled hierarchical fragmentation method. Then matched molecular pairs that differ by only one chemical transformation (i.e., addition or substitution of fragments) were identified and analyzed. The difference in solubility for each matched molecular pair was calculated, and the impact of the corresponding chemical transformation on solubility was investigated. The final product of this study was a fragment-solubility knowledgebase containing relative contributions to solubility of various medicinal chemistry design elements (R-groups, linkers, and rings). Structural modifications that might improve solubility profiles, that is, addition/deletion/substitution of fragments, could be derived from this knowledgebase. This knowledgebase could be used as an expert tool in lead optimization to improve solubility profiles of compounds, and the analysis method could be applied to study other biological and ADMET properties of organic compounds.


Intraoperative identification of parathyroid glands with methylene blue infusion.
Intraoperative staining of parathyroid glands with methylene blue was used in 120 cervical explorations for hyperparathyroidism. The dye clearly stained 66 of 67 adenomas (98%) and 194 of 198 hyperplastic glands (98%). No recurrences were observed in 66 patients undergoing surgery for an adenoma. Six of 48 patients (12%) had recurrences of hyperplasia of the parathyroid glands. We found methylene blue to be an effective, safe, and easy applicable method to quickly identify abnormal parathyroid glands, thereby considerably shortening the operating time.


Image guided oral implantology and its application in the placement of zygoma implants.
The application of zygoma implants proposes a successful treatment for functional reconstruction of maxillary defects. However, the placement of zygoma implants is not without risk due to anatomically complex operation sites. Aiming at minimizing the risks and improving the precision of the surgery, an image guided oral implantology system (IGOIS) is presented in this study to transfer the preoperative plan accurately to the operating theatre. The principle of IGOIS is introduced in detail, including the framework, 3D-reconstruction, preoperative planning, registration, and the motion tracking algorithm. The phantom experiment shows that fiducial registration error (FRE) and TRE (target registration error) of IGOIS are, respectively, 1.12mm and 1.35mm. With respect to the overall accuracy, the average distance deviations at the coronal and apical point of the implant are, respectively, 1.36+/-0.59mm and 1.57+/-0.59mm, while average angle deviation between the axes of the planned and the actual implant is 4.1 degrees +/-0.9 degrees . A clinical report for a patient with a severely atrophic maxilla demonstrates that the major advantage of this computer-aided navigation technology lies in its accuracy, reliability, and flexibility.


Cadherin-16 (CDH16) immunohistochemistry: a useful diagnostic tool for renal cell carcinoma and papillary carcinomas of the thyroid.
Cadherin-16 (CDH16) plays a role in the embryonal development in kidney and thyroid. Downregulation of CDH16 RNA was found in papillary carcinomas of the thyroid. To determine the expression of CDH16 in tumors and to assess the diagnostic utility a tissue microarray containing 15,584 samples from 152 different tumor types as well as 608 samples of 76 different normal tissue types was analyzed. A membranous CDH16 immunostaining was predominantly seen in thyroid, kidney, cauda epididymis, and mesonephric remnants. In the thyroid, CDH16 staining was seen in 100% of normal samples, 86% of follicular adenomas, 60% of follicular carcinomas, but only 7% of papillary carcinomas (p < 0.0001). CDH16 positivity was frequent in nephrogenic adenomas (100%), oncocytomas (98%), chromophobe (97%), clear cell (85%), and papillary (76%) renal cell carcinomas (RCCs), various subtypes of carcinoma of the ovary (16-56%), various subtyped of carcinomas of the uterus (18-40%), as well as in various subtypes of neuroendocrine neoplasms (4-26%). Nineteen further tumor entities showed a weak to moderate CDH16 staining in up to 8% of cases. Our data suggest CDH16 as a potential diagnostic marker-as a part of a panel-for the identification of papillary carcinomas of the thyroid, nephrogenic adenomas, and the distinction of renal cell tumors from other neoplasms.


Assessment of the reliability of MSI status and dMMR proteins deficiency screening on endoscopic biopsy material in esophagus and gastric adenocarcinoma.
Microsatellite instability (MSI) is a negative predictive factor for neoadjuvant chemotherapy in resectable oesogastric adenocarcinoma and a crucial determinant for immunotherapy. We aimed to evaluate reliability of dMMR/MSI status screening performed on preoperative endoscopic biopsies. Paired pathological samples from biopsies and surgical specimen of oesogastric adenocarcinoma were retrospectively collected between 2009 and 2019. We compared dMMR status obtained by immunohistochemistry (IHC) and MSI status by PCR. dMMR/MSI status on surgical specimen was considered as reference. PCR and IHC were conclusive on biopsies respectively for 53 (96.4%) and 47 (85.5%) of the 55 patients enrolled. IHC was not contributive for 1 surgical specimen. A third reading of IHC was carried out for 3 biopsies. MSI status was observed in 7 (12.5%) surgical specimens. When analyses were contributive, sensitivity and specificity of biopsies for dMMR/MSI were respectively 85% and 98% for PCR vs. 86% and 98% for IHC. Concordance rate between biopsies and surgical specimen was 96.2% for PCR and 97.8% for IHC. Endoscopic biopsies are a suitable source of tissue for dMMR/MSI status determination in oesogastric adenocarcinoma which should be routinely performed at diagnosis to better adapt neoadjuvant treatment. By comparison of dMMR phenotype obtained by immunohistochemistry and MSI status by PCR between match-paired samples of oesogastric cancer's endoscopic biopsies and surgical specimen, we observed that biopsies are a suitable source of tissue for dMMR/MSI status determination.


Application of pH-zone refining hydrostatic countercurrent chromatography (hCCC) for the recovery of antioxidant phenolics and the isolation of alkaloids from Siberian barberry herb.
The development of a fast hCCC method tailored to recover phenolics of Siberian barberry (Berberis sibirica, Berberidaceae) responsible for the observed strong antioxidant activity was performed. Initially, the optimization of extraction procedure was evaluated based on the antiradical potential assessment (DPPH and Folin-Ciocalteu assays). 100 °C methanol ASE extract exhibited the highest antiradical activity (IC50=60 ± 4 μg/mL), and a significant TPC (159 ± 2 mgGAE/g). Thorough determination of phenolic content by UHPLC-DAD-ESI(-)HRMS revealed the presence of 10 phenolics as major constituents, and several groups of alkaloids. pH-zone refining hCCC was chosen as the most promising method for the extract's fractionation due to the ionizable character of its constituents. For this purpose a MtBE-H2O (1:1) system with 10mM TEA and HCl was applied leading to a phenolic fraction, free of alkaloids, with higher antioxidant capacity (IC50=25 μg/mL, TPC=178 mg GAE/g). Additionally, fractionation of alkaloids was achieved resulting isolation of pharmacologically important alkaloids: magnoflorine and berberine.


Persistent embryonic veins in the arteriovenous malformation of the diencephalon.
The diencephalic arteriovenous malformation is produced by the posterior cerebral, posterior choroidal, and anterior choroidal arteries. The abnormal arterialised vessels seen in these malformation represent dorsal and ventral diencephalic veins. The drainage of the shunted blood is primarily into the transverse sinus. This is later diverted medially into the great cerebral vein, with the formation of the basal vein. The medial drainage, in keeping with the normal developmental pattern, is seen frequently. The presence and locations of angiomas are very variable and do not follow any predictable pattern.


N-Propargyl Caffeamide (PACA) Ameliorates Dopaminergic Neuronal Loss and Motor Dysfunctions in MPTP Mouse Model of Parkinson's Disease and in MPP+-Induced Neurons via Promoting the Conversion of proNGF to NGF.
Insufficient production of nerve growth factor (NGF) is implicated in Parkinson's disease (PD). We recently discovered that caffeic acid derivative N-propargyl caffeamide (PACA) not only potentiated NGF-induced neurite outgrowth but also attenuated 6-hydroxydopamine neurotoxicity in neuronal culture. The aim of the present study was to investigate whether PACA could increase NGF levels against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) neurotoxicity in a mouse PD model. We induced parkinsonism in mice by intraperitoneal injection of MPTP for seven consecutive days. Animal motor functions were assessed by rotarod test and pole test. Our results showed that PACA ameliorated motor impairments in MPTP-challenged mice. Based on Western blot analysis and/or immunofluorescence staining of NGF and tyrosine hydroxylase (TH), PACA preserved TH levels in the midbrain substantia nigra pars compacta. PACA also increased NGF expression while it decreased proNGF accumulation. Interestingly, NGF was widely induced in the midbrains including astrocytes. To elucidate the mechanisms by which PACA induces NGF, we focused on the effects of PACA on two neurotrophic signaling pathways, the PI3K and MEK pathways. We found that PACA induced the phosphorylation of Akt, ERK, and CREB against MPTP-mediated alterations. Importantly, PACA increased NGF levels and subsequently induced TrkA activation in MPTP-treated mice. Consistently, PACA also increased NGF levels in dopaminergic PC12 cells and primary rat midbrain neurons against N-methyl-4-phenylpyridinium iodide (MPP+) toxicity. ERK and PI3K inhibitors attenuated the effects of PACA on NGF levels. Collectively, our results suggest that PACA may rescue NGF insufficiency via sequential activation of PI3K/Akt, ERK1/2, and CREB signaling pathways. Graphical Abstract .


Effect of tetrahydroisoquinoline (TIQ), one of endogenous substances inducing parkinsonism, on isolated rat vas deferens.
1. The effect of tetrahydroisoquinoline (TIQ) was examined on isolated rat vas deferens. 2. TIQ shifted the concentration-response curve for norepinephrine towards lower concentrations: the pD2-value of norepinephrine in the presence of TIQ was significantly greater than in its absence. 3. Tyramine-induced contraction in the presence of TIQ decreased by a significant 35% more than in the absence of TIQ. 4. These results indicate that the pharmacological effect of TIQ is due to the inhibition of the neuronal uptake of catecholamines.


Sulfitobacter albidus sp. nov., isolated from marine sediment of Jeju Island.
Strain JK7-1T isolated from marine sediment collected from Jeju Island of South Korea was strictly aerobic, Gram-stain-negative, catalase-positive, oxidase-positive, motile, and rod-shaped bacterium that is circular and convex with white pigment. Strain JK7-1T could grow at 10-30 °C and pH 6-9 with 1-6% (w/v) NaCl. Phylogenetic analysis based on its 16S rRNA gene sequence indicated that strain JK7-1T belonged to genus Sulfitobacter, sharing high sequence similarities with Sulfitobacter undariae W-BA2T (97.90%), Sulfitobacter donghicola KCTC 12864T (97.61%), and Sulfitobacter mediterraneus KCTC 32188T (97.47%). Strain JK7-1T possessed only ubiquinone-10 (Q-10) as a sole respiratory quinone and summed feature 8 as the major fatty acid (81.02%). A dominant polar lipid phosphatidylglycerol was identified in strain JK7-1T. Strain JK7-1T had a complete genome of 3,441,674 bp in length with a mean G + C content of 63.96%. Polyphasic and genomic analyses revealed that strain JK7-1T represented a novel species in the genus Sulfitobacter, for which a name of Sulfitobacter albidus sp. nov. was proposed. Its type strain is JK7-1T (= KCTC 72819T = NBRC 114632T = KMM 6821T).


[Karyotype in acute myeloid leukemia: importance and type of aberrations in 30 patients at diagnosis].
Cytogenetics in AML at diagnosis is a well defined prognostic tool. The authors analized karyotype (KT) and clinical data of newly diagnosed AML patients. Thirty patients were studied, 16 male and 14 female. Age ranged from 19 to 84 years. Diagnostic criteria were based on WHO classification, immunophenotyping and G banding cytogenetics. They were treated according to standard protocol (daunorrubicin and cytarabine - 3+7) and those who had Acute Promyelocytic Leukemia additionally received ATRA. KT success rate was 84%. According to KT patients were divided into 4 groups: favourable prognosis (FP) (6) (t(8;21), t(15;17)); intermediary prognosis (IP) (7)(four normal karyotypes, + 8, t(1;2) and del 18(q)); unfavourable prognosis (UP); and 3 secondary AML; two evolving from prior Mylelodysplastic Syndrome and one presenting as an initial blast crisis of chronic myeloid leukemia. The median age of FP was 23 years while UP was 60 years (p<0.003). In the FP, 5/6 (83%) achieved complete remission (CR) while only 1/7 (20%)in the IP and 1/8 (12,5%) in the UP. There was a tendency of higher leukocyte count in the unfavourable group. The rate of karyotype aberrations in AML was 80% and in accordance to literature data (65-95%). There was a clear difference in CR rates between favourable and unfavourable prognosis group.


Energy Conversion Processes with Perovskite-type Materials.
Mixed oxides derived from the perovskite structure by combination of A- and B-site elements and by partial substitution of oxygen provide an immense playground of physico-chemical properties. Here, we give an account of our own research conducted at the Paul Scherrer Institute on perovskite-type oxides and oxynitrides used in electrochemical, photo(electro)chemical and catalytic processes aimed at facing energy relevant issues.


Calculation of power for matched pair studies when randomization is by group.
A formula is given for the calculation of the statistical power of paired intervention trials in which the units of randomization are groups rather than individuals. Factors affecting the power of such trials are also investigated and an example is given where the power of group randomization is compared to that of individual randomization.


Triple-site pacing for cardiac resynchronization in permanent atrial fibrillation - Acute phase results from a prospective observational study.
Multi-site pacing is emerging as a new method for improving response to cardiac resynchronization therapy (CRT), but has been little studied, especially in patients with atrial fibrillation. We aimed to assess the effects of triple-site (Tri-V) vs. biventricular (Bi-V) pacing on hemodynamics and QRS duration. This was a prospective observational study of patients with permanent atrial fibrillation and ejection fraction <40% undergoing CRT implantation (n=40). One right ventricular (RV) lead was implanted in the apex and another in the right ventricular outflow tract (RVOT) septal wall. A left ventricular (LV) lead was implanted in a conventional venous epicardial position. Cardiac output (using the FloTrac™ Vigileo™ system), mean QRS and ejection fraction were calculated. Mean cardiac output was 4.81±0.97 l/min with Tri-V, 4.68±0.94 l/min with RVOT septal and LV pacing, and 4.68±0.94 l/min with RV apical and LV pacing (p<0.001 for Tri-V vs. both BiV). Mean pre-implantation QRS was 170±25 ms, 123±18 ms with Tri-V, 141±25 ms with RVOT septal pacing and LV pacing and 145±19 with RV apical and LV pacing (p<0.001 for Tri-V vs. both BiV and pre-implantation). Mean ejection fraction was significantly higher with Tri-V (30±11%) vs. Bi-V pacing (28±12% with RVOT septal and LV pacing and 28±11 with RV apical and LV pacing) and pre-implantation (25±8%). Tri-V pacing produced higher cardiac output and shorter QRS duration than Bi-V pacing. This may have a significant impact on the future of CRT.


Molecular and biochemical effects of the antifouling DCOIT in the mussel Perna perna.
Biological fouling is an unwanted phenomenon that results in economic losses to the shipping industry. To prevent fouling, antifouling paints are used. DCOIT (4,5- dichloro-2-n-octyl-4-isothiazolin-3-one) is a biocide present in many antifouling paint formulations, and is toxic to a wide range of organisms. The aim of the present study was to evaluate the effects of DCOIT on oxidative stress indicators of the brown mussel, Perna perna. Molecular (SOD-like, GSTO-like and MGST-like mRNA levels) and biochemical (activities of superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST), and levels of glutathione (GSH), reactive oxygen species (ROS) and protein carbonyls (PCO)) components were evaluated. Further, levels of biomarkers were assessed in the gills and digestive glands of mussels. Bivalves were exposed to DCOIT (control, 0.1 μg/L and 10 μg/L) for up to 96 h. DCOIT exposure decreased GSH content in gills. Moreover, exposure to DCOIT also decreased CAT activity in the gills and digestive glands of mussels. GST activity increased in digestive gland after exposure for 24 h to both concentrations of DCOIT tested. SOD activity, ROS levels and PCO content were not affected by exposure to the contaminant. Regarding the molecular biomarkers evaluated, DCOIT exposure altered mRNA levels of SOD-like in both tissues after 24 and 96 h of exposure, and decreased MGST-like mRNA levels in the digestive gland after 96 h of exposure to the chemical. These findings suggested that exposure to DCOIT may alter the biochemical and molecular functioning of P. perna, which may harm the species.


Comparison of frailty in patients with nontuberculous mycobacterial lung disease and bronchiectasis: a prospective cohort study.
The incidence of nontuberculous mycobacterial lung disease (NTM-LD) peaks in middle- and old age groups, coinciding with senescence; thus, chronic infectious diseases can accelerate frailty and worsen mental health in the elderly. In this study, we aimed to compare the prevalence of physical and psychiatric frailty between patients with NTM-LD and bronchiectasis (BE). The Kihon Checklist Questionnaire (KCQ) was used to assess physical and psychiatric frailties and identify those at risk of requiring care among patients with newly diagnosed NTM-LD and BE. Additionally, the Hospital Anxiety and Depression Scale (HADS) scores and chronic inflammatory biomarkers of the alveolar region (surfactant protein [SP]-A, SP-D, and human cationic antibacterial protein [hCAP]/LL-37) were assessed and compared between NTM-LD and BE patients. There were no significant differences in the background characteristics between the 33 NTM and 36 BE patients recruited. The KCQ revealed that the proportion of frail NTM patients at diagnosis was higher than that of frail BE patients (48.5% vs. 22.2%, p = 0.026). HADS scores were significantly higher in the NTM group than in the BE group (p < 0.01). Bronchoalveolar lavage fluid (BALF) hCAP/LL-37 and SP-D levels were significantly higher (p = 0.001), but serum hCAP/LL-37 levels were significantly lower in the NTM group than in the BE group (p = 0.023). However, there were no significant differences in the BALF and serum SP-D levels between the two groups. The number of frail NTM patients at diagnosis was significantly higher than that of frail BE patients. Biomarker analysis suggested that the former had more localized lung inflammation than the latter. This trial was prospectively registered in the Clinical Trials Registry (UMIN 000027652).


Surface anatomy of branchial food traps of tadpoles: A comparative study.
Branchial food traps are regions of specialized secretory tissue in the tadpole pharynx, where suspended food particles are trapped in mucus. Light and scanning electron microscopy were used to study branchial food traps from larvae of ten anuran families (36 species). Most anuran larvae from "advanced" (suborder Neobatrachia) families (e.g., Hylidae, Ranidae, Bufonidae) have distinct secretory pits at the posterior margins of the branchial food traps and secretory ridges elsewhere on these surfaces. The apices of columnar PAS-positive, secretory cells are exposed on the floors of the secretory pits or in rows at the tops of the secretory ridges (secretory zone). Tadpoles from most "archaic" (suborder Archaeobatrachia) families (Ascaphidae, Discoglossidae and Pelobatidae) either lack secretory pits, or have them poorly defined. They also lack secretory ridges but have columnar, mucus-secreting cells whose apices are exposed in a seemingly random fashion in the branchial food traps. Rhinophrynus (Archaeobatrachia: Rhinophrynidae) has secretory ridges, but the apices of secretory cells are not arranged in rows at the tops of the ridges; instead they erupt singly or in small clusters on the epithelial surface, in a pattern similar to that in Ascaphus, the discoglossids and the pelobatids. It is proposed that the generalized condition for the branchial food trap mucosa is one where the apices of secretory cells are exposed haphazardly on a flat epithelium and the derived condition is one where the surface is organized into ridges. The morphology of the branchial food traps in Rhinophrynus suggests that, phylogenetically, ridges preceded the coalescing of secretory cell apices into distinct rows. Pipidae and Microhylidae have unique patterns in the gross and microanatomy of their branchial food traps specific to their families. Branchial food trap morphology relates to diets of tadpoles as well as to taxonomy. Obligate macrophagous (e.g., carnivorous) tadpoles, irrespective of family, tend to have reduced branchial food traps, regularly lack secretory ridges and, in extreme cases, lack columnar mucus-secreting cells. Obligate microphagous forms (midwater suspension feeding of Xenopus, microhylids and Agalychnis), have straight parallel secretory ridges with narrow secretory zones and shallow troughs between the ridges. Secretory ridges may help to form mucus strands in which food particles are trapped, but they are not essential for planktonic entrapment. The hydrodynamic implications of the various topographic patterns remain unclear.


An emerging role for stress granules in neurodegenerative disease and hearing loss.
Stress granules (SGs) are membrane-less cytosolic assemblies that form in response to stress (e.g., heat, oxidative stress, hypoxia, viral infection and UV). Composed of mRNA, RNA binding proteins and signalling proteins, SGs minimise stress-related damage and promote cell survival. Recent research has shown that the stress granule response is vital to the cochlea's response to stress. However, emerging evidence suggests stress granule dysfunction plays a key role in the pathophysiology of multiple neurodegenerative diseases, several of which present with hearing loss as a symptom. Hearing loss has been identified as the largest potentially modifiable risk factor for dementia. The underlying reason for the link between hearing loss and dementia remains to be established. However, several possible mechanisms have been proposed including a common pathological mechanism. Here we will review the role of SGs in the pathophysiology of neurodegenerative diseases and explore possible links and emerging evidence that they may play an important role in maintenance of hearing and may be a common mechanism underlying age-related hearing loss and dementia.


Early prediction of neoadjuvant treatment outcome in locally advanced breast cancer using parametric response mapping and radial heterogeneity from breast MRI.
Early prediction of nonresponse is essential in order to avoid inefficient treatments. To evaluate if parametrical response mapping (PRM)-derived biomarkers could predict early morphological response (EMR) and pathological complete response (pCR) 24-72 hours after initiation of chemotherapy treatment and whether concentric analysis of nonresponding PRM regions could better predict response. This was a retrospective analysis of prospectively acquired cohort, nonrandomized, monocentric, diagnostic study. Sixty patients were initially recruited, with 39 women participating in the final cohort. A 1.5T scanner was used for MRI examinations. Dynamic contrast-enhanced (DCE)-MR images were acquired at baseline (timepoint 1, TP1), 24-72 hours after the first chemotherapy (TP2), and after the end of anthracycline treatment (TP3). PRM was performed after fusion of T1 subtraction images from TP1 and TP2 using an affine registration algorithm. Pixels with an increase of more than 10% of their value (PRMdce+) were corresponding nonresponding regions of the tumor. Patients with a decrease of maximum diameter (%dDmax) between TP1 and TP3 of more than 30% were defined as EMR responders. pCR patients achieved a residual cancer burden score of 0. T-test, receiver operating characteristic (ROC) curves, and logistic regression were used for the analysis. PRM showed a statistical difference between pCR response groups (P < 0.01) and AUC of 0.88 for the prediction of non-pCR. Logistic regression analysis demonstrated that PRMdce+ and Grade II were significant (P < 0.01) for non-pCR prediction (AUC = 0.94). Peripheral tumor region demonstrated higher performance for the prediction of non-pCR (AUC = 0.85) than intermediate and central zones; however, statistical comparison showed no significant difference. PRM could be predictive of non-pCR 24-72 hours after initiation of chemotherapy treatment. Moreover, the peripheral region showed increased AUC for non-pCR prediction and increased signal intensity during treatment for non-pCR tumors, information that could be used for optimal tissue sampling. 1 Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2020;51:1403-1411.


5-Fluorouracil infusions and fractionated doses of radiation: studies with a murine squamous cell carcinoma.
The present investigation describes the effects on a murine squamous cell tumor of combined treatment using radiation and 5-Fluorouracil (5FU), with emphasis on 5FU infusions. The tumor, SCC VII/To, was grown intramuscularly in the hind legs of C3H mice. Radiation was given locally with 100 kVp X rays either alone or in combination with 5FU by i.p. bolus injections or 4-14 day infusions using subcutaneously implanted mini-osmotic pumps. Studies with radiation alone indicated regrowth delay increased with total dose. This increase was less for fractionated than single doses. The effects of 5FU alone were compared using i.p. injections or 4, 7 or 14 day infusions. Tumor response to single i.p. bolus injections or 4 day infusions were not significantly different. Up to total drug doses of 200 mg/kg, 14 day infusions were least effective on regrowth delay, 4 day infusions were intermediate and 7 day infusions were most effective. Above total drug doses of 200 mg/kg, effects of 14 day infusions on regrowth delay increased rapidly. The LD50 for single i.p. bolus injections and 7 day infusions were similar, 230 and a total drug dose of 270 mg/kg, respectively. When a 7 day infusion of 5FU (133 mg/kg) was combined with increasing total radiation doses (1 or 5 fractions), the increase in regrowth delay was additive. Combining a fractionated dose of 5 Gy per day for 5 days (5/5 Gy) with increasing total drug doses of 5FU (single i.p. bolus injections or 4, 7 or 14 day infusions) resulted in regrowth delays that were dependent on the total dose of 5FU. Administering a 133 mg/kg dose of 5FU (via a single i.p. bolus injection or 7 day infusion) starting 2 days before, during, or immediately after 5/5 Gy gave the same regrowth delay, indicating no effect of drug sequencing. In conclusion, the above data indicate that (a) 5FU infusions (greater than 4 days) are more effective than 5FU injections on regrowth delay and (b) combinations of 5FU and radiation, produce an additive tumor response, which occurs independent of mode, schedule, and time of 5FU administration, and is dependent on 5FU total dose.


Exploring the bioactivity potential of Leonotis nepetifolia: phytochemical composition, antimicrobial and antileishmanial activities of extracts from different anatomical parts.
Leonotis nepetifolia (L.) Br. (Lamiaceae) is an African shrub popularly known as 'cordão-de-frade' in Brazil, traditionally used to treat infectious diseases, among other uses. This study aimed to investigate the phytochemical composition of hydroethanolic extracts from L. nepetifolia prepared from stems, leaves, roots and glomerulus, as well as their cytotoxicity, antileishmanial and antimicrobial activities. The chemical composition of the extracts was assessed by UPLC-ESI-MS/MS, whereas the antileishmanial activity was evaluated against promastigote and amastigote forms of Leishmania amazonensis. Cytotoxicity was tested on murine macrophages and the antimicrobial activity was investigated by a microdilution assay against several strains of fungi, Gram-positive and Gram-negative bacteria. The flavonoids apigenin, cirsiliol apigenin-7-O-glucoside, luteolin, luteolin-4'-O-glucoside, luteolin-4'-O- glucuronide and luteolin-7-O-glucoside were identified in all tested extracts. Extracts from leaves and roots showed more potent antileishmanial activity (IC50 32.90 µg mL-1 and 57.70 µg mL-1, respectively) against amastigotes forms in comparison to the other extracts. The leaf extract inhibited Bacillus cereus and Staphylococcus aureus growth (125 µg mL-1 and 100 µg mL-1, respectively), and also showed anti-Candida activity (10-125 µg mL-1). The biological effect can be related to the identified flavonoids. Our findings disclose the potential of L. nepetifolia as a source of bioactive compounds for the development of new therapeutic options for treating infectious diseases, especially flavonoids.


Evidence for the contribution of the host species to the extent of antigenic variation of N1 influenza virus neuraminidase.
N1 influenza virus neuraminidases (NA) derived from avian, swine and human virus isolates, including the genetically related classic strains A/FPV/Rostock/34, A/Swine/1976/31, A/PR8/34 and A/FM1/47, were analysed serologically by neuraminidase inhibition (NI), inhibition of virus release (IVR) and competitive radio-immunoassays (competitive RIA). Comparing the three tests, competitive RIA appeared to be more reliable than NI and IVR for a quantitative assessment of antigenic relatedness. Together with evidence presented by others, these studies indicate that the host species contributes to the extent of antigenic variation of NAses. In contrast to NAses of human viruses where antigenic drift occurs readily, NAses of animal influenza viruses, from birds or mammalians, undergo far fewer antigen changes.


Intestinal adaptation following jejuno-ileal bypass.
The changes in functional and excluded loops were studied in two groups of patients at intervals up to 5 years after jejuno-ileal bypass. Macroscopic and histological observations confirmed that the compensatory increase of the absorbing surface of the functioning loop occurs, with an increase in length and width of the loop, hypertrophy of villi and microvilli, and increase in number and geometrical surface of the villous cells. In the excluded intestinal loop, atrophy occurs, evidenced by the reduction in number and size of microvilli, even if the height of villi may appear normal. The bacteriological studies of the functioning and excluded loops show bacterial colonization, which was not constant over the course of time.


Effects of cryptolepine on collagen-induced aggregation and on the mobilization and metabolism of arachidonic acid by rabbit platelets.
1. We examined the effect of cryptolepine on collagen-induced aggregation and on the mobilization, and metabolism of arachidonic acid in rabbit platelets. 2. Preincubation of platelets with cryptolepine (50-100 microM) did not affect the primary wave of aggregation but resulted in a dose-dependent, surmountable inhibition of the secondary wave of aggregation induced by collagen (5 micrograms/ml). The inhibition by cryptolepine was greater when cryptolepine was incubated with the platelets after the peak of the primary wave of aggregation. 3. Cryptolepine (50-100 microM) dose-dependently inhibited thrombin (1.5 U/ml) and A23187 (2.5 microM)-induced release of 14C[AA] from platelet membrane phospholipid pools. The percentage inhibition of A23187-induced 14C[AA] release was 31.3 +/- 4.3% (50 microM) and 79.3 +/- 5.4% (100 microM), while thrombin-induced release was inhibited by 39.2 +/- 2.4% (50 microM) and 68.2 +/- 3.6% (100 microM). 4. At near maximal concentration (100 microM) which significantly inhibited secondary aggregatory response and 14C[AA] release, cryptolepine had no effect on the platelet metabolism of 14C[AA] to thromboxane B2, HHT and 12 HETE. 5. The present findings suggest that cryptolepine inhibited collagen-induced secondary aggregation through a selective antiphospholipase-like activity. There was no effect on platelet cyclooxygenase and lipoxygenase activities of platelets.


Influence of Microbubbles on Free Radical Generation by Ultrasound in Aqueous Solution: Dependence of Ultrasound Frequency.
The influence of microbubbles on sonochemical efficiencies has been investigated under 28, 45, and 100 kHz ultrasound irradiation. For the 28 and 100 kHz ultrasound frequencies, microbubbles suppressed the I3(-) formation from KI solution as well as the 7-hydroxycoumarin formation from coumarin solution caused by the ultrasonic irradiation. On the other hand, for the 45 kHz ultrasound frequency, microbubbles enhanced the I3(-) formation from KI solution as well as 7-hydroxycoumarin formation from coumarin solution caused by the ultrasonic irradiation. Detection of H2O2 after the irradiation of ultrasound in the presence or absence of microbubbles was also performed, and it was found that H2O2 formation was enhanced only when microbubbles were introduced under the 45 kHz ultrasonic irradiation, which was in good agreement with the results of KI oxidation dosimetry measurements and of coumarin fluorescent probe measurements. Based on these present results, plausible mechanisms that explain the dependence of the ultrasound frequency on the enhancement and suppression of free radical formation in the presence of MBs were proposed.


lck suppresses gene expression from various promoters including human T-cell leukemia virus type I promoter.
The T-lymphocyte-specific tyrosine kinase gene, lck, is expressed in T-lymphocyte cell lines, except for several human T-cell leukemia virus type I(HTLV-I)-transformed T-lymphocyte cell lines, which produce HTLV-I. By introducing an lck-expression vector, we found that lck product suppresses gene expression from HTLV-I promoter in a transient assay. Moreover, various other promoters of cellular genes or viruses were found to have their transcriptional activity repressed by lck.


Atrialized right ventricular chamber as a source of ventricular tachycardia in Ebstein's anomaly. Analysis of two successful catheter ablation cases.
Ventricular tachycardia in Ebstein's anomaly patients is rare and increases the risk of sudden death up to 6 times. We present two cases of Ebstein's anomaly, the first of them with a history of Glenn surgery and biological prosthesis at tricuspid position and the second case without surgical repair. Both admitted to the emergency room due to ventricular tachycardia poorly tolerated. Detailed substrate characterization and pace mapping showed fragmented signals in the area of atrialized right ventricle and correlated were pace mapping reproduced morphology identical to the clinical VT, ablation at this sites were successful without recurrence during follow-up.


Double-well dynamics of noise-driven control activation in human intermittent control: the case of stick balancing.
When facing a task of balancing a dynamic system near an unstable equilibrium, humans often adopt intermittent control strategy: Instead of continuously controlling the system, they repeatedly switch the control on and off. Paradigmatic example of such a task is stick balancing. Despite the simplicity of the task itself, the complexity of human intermittent control dynamics in stick balancing still puzzles researchers in motor control. Here we attempt to model one of the key mechanisms of human intermittent control, control activation, using as an example the task of overdamped stick balancing. In doing so, we focus on the concept of noise-driven activation, a more general alternative to the conventional threshold-driven activation. We describe control activation as a random walk in an energy potential, which changes in response to the state of the controlled system. By way of numerical simulations, we show that the developed model captures the core properties of human control activation observed previously in the experiments on overdamped stick balancing. Our results demonstrate that the double-well potential model provides tractable mathematical description of human control activation at least in the considered task and suggest that the adopted approach can potentially aid in understanding human intermittent control in more complex processes.


Come with me if you want to live: sympatric parasites follow different transmission routes through aquatic host communities.
Community composition, including the relative density of each host species, plays a vital role in the transmission of parasites or disease in freshwater ecosystems. Whereas some host species can effectively transmit parasites, others can act as dead ends (non-viable transmission routes), accumulating large numbers of parasites throughout their life, thus becoming important sinks for parasite populations. Although population sinks have been identified in certain host-parasite systems, robust field estimates of the proportions of parasites that are lost to these hosts are lacking. Here, we quantified the distribution of encysted larval hairworms (phylum Nematomorpha), common parasites in lotic ecosystems, in two subalpine stream communities of New Zealand. With parasite and host population densities calculated per m2, we identified which host species most likely contributed to the transmission of three sympatric hairworm morphotypes identified in both streams, and which species acted as population sinks. We also tested for seasonal patterns and peaks in the abundance of each morphotype in the two communities over the sampling season. Finally, we tested whether hosts emerging from the streams had comparable abundances of hairworm morphotypes throughout the sampling period. For each morphotype, different key sets of host species harboured more hairworms on average (abundance) than others, depending on the stream. For one morphotype in particular, two species of hosts were found to be important population sinks that inhibited over a third of these parasites from completing their life cycle. We also observed a clear peak in abundance for another hairworm morphotype during summer. Our data suggest that hosts emerging from the streams matched their aquatic counterparts with respect to hairworm abundance, indicating no infection-dependent reduction in emergence success. Our findings suggest that, depending on relative community composition, sympatric parasites follow different host transmission pathways, some of which lead to dead ends that potentially impact overall infection dynamics. In turn, this information can help us understand the spread or emergence of disease in both freshwater and terrestrial environments, since hairworms infect terrestrial arthropods to complete their life cycle.


Antagonistic and synergistic effects of lead and selenium in Rattus norvegicus.
Female rats were administered intraperitoneal injections of solutions of lead acetate and sodium selenite. The salt solutions were given singly to 'control' animals and successively to the 'treated' animals in both chronic and acute treatments but with or without a time gap of 1 h in the latter treatment. In the chronic treatments the dosage of lead acetate was kept constant and that of sodium selenite varied while in the acute treatments the ratio of the two salts was kept constant. Degrees of protection afforded by sodium selenite against chromosomal damage caused by lead acetate were assessed.


Distinctive nail pattern following androgen replacement therapy.
A distinctive nail pattern in a patient undergoing androgen replacement therapy is presented hereby. A 47-year-old male patient noticed a peculiar "washboard-like" pattern on his fingernails. He had been undergoing androgen replacement therapy for late onset hypogonadism syndrome. The patient realized his nails were growing faster after his therapy was altered from a tri-weekly basis to a bi-weekly basis. This phenomenon is likely to be attributed to the androgen replacement therapy, as the spacing between the ridges were widening in concordance with the strengthening of the therapy.


CXCL10 as a shared specific marker in rheumatoid arthritis and inflammatory bowel disease and a clue involved in the mechanism of intestinal flora in rheumatoid arthritis.
This study aimed to identify shared specific genes associated with rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) through bioinformatic analysis and to examine the role of the gut microbiome in RA. The data were extracted from the 3 RA and 1 IBD gene expression datasets and 1 RA gut microbiome metagenomic dataset. Weighted correlation network analysis (WGCNA) and machine learnings was performed to identify candidate genes associated with RA and IBD. Differential analysis and two different machine learning algorithms were used to investigate RA's gut microbiome characteristics. Subsequently, the shared specific genes related to the gut microbiome in RA were identified, and an interaction network was constructed utilizing the gutMGene, STITCH, and STRING databases. We identified 15 candidates shared genes through a joint analysis of the WGCNA for RA and IBD. The candidate gene CXCL10 was identified as the shared hub gene by the interaction network analysis of the corresponding WGCNA module gene to each disease, and CXCL10 was further identified as the shared specific gene by two machine learning algorithms. Additionally, we identified 3 RA-associated characteristic intestinal flora (Prevotella, Ruminococcus, and Ruminococcus bromii) and built a network of interactions between the microbiomes, genes, and pathways. Finally, it was discovered that the gene CXCL10 shared between IBD and RA was associated with the three gut microbiomes mentioned above. This study demonstrates the relationship between RA and IBD and provides a reference for research into the role of the gut microbiome in RA.


Clarithromycin increases the release of heat shock protein B from Helicobacter pylori.
Clarithromycin (CAM) may have certain indirect effects on Helicobacter pylori (H. pylori) other than its inhibitory activity on bacterial growth, as indicated in other infections with Gram-negative micro-organisms. In the present study, we examined the effects of lower concentrations of CAM on the release of heat shock protein B (HspB), one of the major antigenic proteins from H. pylori cells, as well as the changes in humoral immune response and histological degree of antral gastritis in patients who received eradication therapy with CAM. The H. pylori strain 26695 and three CAM-resistant clinical isolates were cultured in broth with and without CAM (2-500 ng/mL). Expression of H. pylori proteins was examined by two-dimensional (2D)-electrophoresis followed by N-terminal amino acid sequencing. Changes in host immune response and histological degree of antral gastritis were monitored in patients with peptic ulcer disease who received H. pylori eradication therapy. 2D electrophoresis showed 26 spots in extracellularly released proteins with different profiles from those in cytoplasmic proteins. The release of HspB increased after incubation with CAM (30-500 ng/mL) in all three H. pylori clinical isolates tested. Patients with failed H. pylori eradication after triple therapy with CAM, but not those with failed eradication after dual therapy without CAM, showed an increase in serum IgG1 and IgG2 antibodies against HspB along with a decrease in the degree of neutrophil and H. pylori colonization density in tissue sections. CAM may induce a humoral immune response against H. pylori and a decrease in gastric mucosal inflammation through up-regulation of the release of HspB from the bacteria in infected patients.


Identification of histidine-119 as the target in the site-specific inactivation of ribonuclease A by ferrate ion.
Ferrate ion, a powerful oxidant which is an analog of orthophosphate ion, has previously shown some promise as a site-specific probe of enzymes which interact with phosphate compounds. In order to explore the general applicability of this reagent, it has been tested against ribonuclease A, an enzyme whose structure and active center have been well described. Treatment with a molar ratio of ferrate to enzyme of less than 20 leads to a loss of 87% of the activity. The known competitive inhibitors, 2'-cytidylic acid, inorganic pyrophosphate, and orthophosphate all protect the enzyme from inactivation. Inactivation is accompanied by a loss of the capacity to bind 2'-cytidylic acid. Ferrate inactivation at pH 5.0 is accompanied by the modification of only one amino acid. The amino acid which was identified by amino acid and sequence analyses of peptide fragments obtained by cyanogen bromide treatment and selective proteolysis proved to be histidine-119, whose essential role at the active center has long been established.


Nitric oxide participates in the induction of brain ischemic tolerance via activating ERK1/2 signaling pathways.
The present study was undertaken to observe in vivo changes of expression and phosphorylation of ERK1/2 proteins during brain ischemic preconditioning and effects of inhibiting generation of nitric oxide (NO) on the changes to determine the role of ERKs in the involvement of NO participating in the acquired tolerance. Fifty-five Wistar rats were used. Brain ischemic preconditioning was performed with four-vessel occlusion for 3 min. Total ERK1/2 proteins and phospho-ERK1/2 in the CA1 hippocampus were assayed with Western immunoblot. Total ERK1/2 proteins did not change in period from 5 min to 5 days of reperfusion after preconditioning stimulus. While the level of phospho-ERK1/2 increased obviously to 223, 237, 300, 385 and 254% of sham level at times of 5 min, 2 h, 1, 3 and 5 days after preconditioning stimulus, respectively (P < 0.01). Administration of L-NAME, an inhibitor of NO synthase, 30 min prior to preconditioning stimulus failed to induce change in total ERK1/2 proteins (P > 0.05). However, phospho-ERK1/2 increased only to 138 and 176% of sham level at 2 h and 3 days after preconditioning stimulus, respectively, when animals were pretreated with L-NAME. The magnitudes of the increase were obviously low compared with those (237 and 385%) in animals untreated with L-NAME at corresponding time points (P < 0.01), which indicated that phosphorylation of ERK1/2 normally induced by preconditioning stimulus was blocked apparently by administration of L-NAME. The results suggested that phosphorylation of ERK1/2, rather than synthesis of ERK1/2 proteins, was promoted in brain ischemic preconditioning, and that the promotion was partly mediated by NO signal pathway.


Elder suicide: a gate keeper strategy for home care.
Although home care and hospice patients are admitted with many primary and secondary diagnoses, the importance of identifying elders with the potential for suicide should still be uppermost in the professional's assessment and ongoing evaluation. This article has given many specific suggestions for professionals and organizations to consider and implement in addressing this important problem.


A glycoprotein B-neutralizing antibody structure at 2.8 Å uncovers a critical domain for herpesvirus fusion initiation.
Members of the Herpesviridae, including the medically important alphaherpesvirus varicella-zoster virus (VZV), induce fusion of the virion envelope with cell membranes during entry, and between cells to form polykaryocytes in infected tissues. The conserved glycoproteins, gB, gH and gL, are the core functional proteins of the herpesvirus fusion complex. gB serves as the primary fusogen via its fusion loops, but functions for the remaining gB domains remain unexplained. As a pathway for biological discovery of domain function, our approach used structure-based analysis of the viral fusogen together with a neutralizing antibody. We report here a 2.8 Å cryogenic-electron microscopy structure of native gB recovered from VZV-infected cells, in complex with a human monoclonal antibody, 93k. This high-resolution structure guided targeted mutagenesis at the gB-93k interface, providing compelling evidence that a domain spatially distant from the gB fusion loops is critical for herpesvirus fusion, revealing a potential new target for antiviral therapies.


Mechanism of transcriptional activation by FIS: role of core promoter structure and DNA topology.
The Escherichia coli DNA architectural protein FIS activates transcription from stable RNA promoters on entry into exponential growth and also reduces the level of negative supercoiling. Here we show that such a reduction decreases the activity of the tyrT promoter but that activation by FIS rescues tyrT transcription at non-optimal superhelical densities. Additionally we show that three different "up" mutations in the tyrT core promoter either abolish or reduce the dependence of tyrT transcription on both high negative superhelicity and FIS in vivo and infer that the specific sequence organisation of the core promoter couples the control of transcription initiation by negative superhelicity and FIS. In vitro all the mutations potentiate FIS-independent untwisting of the -10 region while at the wild-type promoter FIS facilitates this step. We propose that this untwisting is a crucial limiting step in the initiation of tyrT RNA synthesis. The tyrT core promoter structure is thus optimised to combine high transcriptional activity with acute sensitivity to at least three major independent regulatory inputs: negative superhelicity, FIS and ppGpp.


RNase E biomolecular condensates stimulate PNPase activity.
Bacterial Ribonucleoprotein bodies (BR-bodies) play an essential role in organizing RNA degradation via phase separation in the cytoplasm of bacteria. BR-bodies mediate multi-step mRNA decay through the concerted activity of the endoribonuclease RNase E coupled with the 3'-5' exoribonuclease Polynucleotide Phosphorylase (PNPase). In vivo, studies indicated that the loss of PNPase recruitment into BR-bodies led to a significant build-up of RNA decay intermediates in Caulobacter crescentus. However, it remained unclear whether this is due to a lack of colocalized PNPase and RNase E within BR-bodies or whether PNPase's activity is stimulated within the BR-body. We reconstituted RNase E's C-terminal domain with PNPase towards a minimal BR-body in vitro to distinguish these possibilities. We found that PNPase's catalytic activity is accelerated when colocalized within the RNase E biomolecular condensates, partly due to scaffolding and mass action effects. In contrast, disruption of the RNase E-PNPase protein-protein interaction led to a loss of PNPase recruitment into the RNase E condensates and a loss of ribonuclease rate enhancement. We also found that RNase E's unique biomolecular condensate environment tuned PNPase's substrate specificity for poly(A) over poly(U). Intriguingly, a critical PNPase reactant, phosphate, reduces RNase E phase separation both in vitro and in vivo. This regulatory feedback ensures that under limited phosphate resources, PNPase activity is enhanced by recruitment into RNase E's biomolecular condensates.


Comparison of primary and secondary closure with a buccal mucosal-advancement flap on postoperative course after mandibular impacted third molar surgery.
The purpose of this study was to compare primary and secondary wound closure with a buccal mucosal-advancement flap technique on the postoperative course after mandibular impacted third molar surgery. The study was conducted on 150 patients who required surgical removal of impacted mandibular third molars under local anesthesia. The study subjects were divided into three groups of 50 patients each, based on the type of closure over the third molar socket. Patients in group I underwent primary closure of the socket with hermetic suturing of the flap, including the vertical release. In group II, a secondary closure was performed, leaving the socket communicating with the oral cavity. In group III, a buccal mucosal-advancement flap technique was employed to achieve primary closure of the flap over the socket while leaving the anterior vertical release, generously patent. All the patients were assessed for pain using the visual analogue scale (VAS), swelling, and mouth opening at postoperative intervals of 2, 4, and 7 days. The wound healing was assessed on day 7. Patients in the buccal mucosal-advancement flap group had significantly less pain and swelling and increased mouth opening compared with primary and secondary closure. Wound dehiscence was seen in 18 patients and alveolar osteitis in 4 patients in primary closure. Delayed wound healing with food accumulation was seen in 6 patients in secondary closure. No complications of flap dehiscence or breakdown were observed in the buccal mucosal-advancement flap group. This study concludes that the buccal mucosal-advancement flap technique was a superior closure technique with less pain, swelling, trismus, and satisfactory wound healing compared with both primary and secondary closure after mandibular third molar surgery.


Transceive surface coil array for magnetic resonance imaging of the human brain at 4 T.
As the static magnetic field strength used in human magnetic resonance imaging increases, the wavelength of the corresponding radiofrequency field becomes comparable to the dimensions of the coil and volume of interest. The dielectric resonance effects that arise in this full wavelength regime may be partially compensated for through the use of surface coils. A novel high-field (4 T) transceive surface coil array is presented that allows arbitrary surface coil placement and size while maintaining the ability to independently transmit and/or receive through conventional 50-ohm power amplifiers and preamplifiers, respectively. A ninefold signal-to-noise ratio (SNR) increase is shown in close proximity to the transceive array and there is an overall 38% increase throughout the entire brain volume in comparison to the standard hybrid birdcage coil. Furthermore, the ability to independently transmit and receive through each surface coil within this array enables transmit and/or receive-only fast parallel imaging techniques to be employed while maintaining the increased SNR sensitivity inherent to surface coil designs.