Factors that influence perforator vein closure rates using radiofrequency ablation, laser ablation, or foam sclerotherapy.
Perforator vein closure for the treatment of advanced chronic venous insufficiency has been shown to be effective using radiofrequency ablation (RFA), endovenous laser ablation (EVLA), or ultrasound-guided foam sclerotherapy (UGFS). The objective of the study was to compare these three modalities and attempt to identify factors that might predict treatment failure. A retrospective review of a prospectively managed database of perforator vein treatments performed at a three centers within a single institution from February 2013 to July 2014. The modality for perforator closure was left to the discretion of the treating physician. A Duplex scan was performed at 2 weeks after the procedure. Standard statistical methods were used to compare subgroup characteristics. Univariate and multivariate analyses were performed using SAS v9.3. We performed 296 perforator ablations on 112 patients. Superficial venous reflux was appropriately treated before perforator ablation. Of the 296 procedures, 62 (21%) underwent EVLA, 93 (31%) RFA, and 141 (48%) UGFS. The indications for intervention in most patients were C5 and C6 disease (67%). At 2 weeks, closure rates were significantly lower for UGFS (57%) compared with RFA (73%; P = .05) but failed to reach significance compared with EVLA (61%; P = .09). When patients were first treated with UGFS and closure failed, thermal ablation was then successful in 85% (P = .03) of EVLA and 89% (P = .003) of RFAs as a secondary procedure, compared with initial closure rates. Systemic anticoagulation, perforator size, and presence of deep vein reflux did not affect closure rates for any modality. Factors that were predictive of failure were body mass index >50 with closure rates of only 37% for all modalities. There were five postprocedure deep venous thromboses found (5%). One patient had an isolated gastrocnemius thrombus after undergoing UGFS and the other four had focal tibial vein thrombosis without extension into the popliteal vein. In this study we compared EVLA, RFA, and UGFS for the treatment of incompetent perforating veins. RFA was found to be the most reliable means of perforator closure and was significantly better than UGFS. Morbid obesity (body mass index >50) predicted failure of perforator closure in all groups. Failure of UGFS as an initial treatment led to increased perforator closure when thermal ablation was used as a secondary technique.


[Structural studies on tubulin in flat sheets formed in the presence of zinc].
Structure of the tubulin molecule was determined from microtubule images by methods of three dimensional reconstruction. We detected two types of zinc-induced sheets with different space latticies. Using the model of the tubulin molecule obtained by three dimensional reconstruction, the relationship of its projections was established by the method of optical filtration. Structural peculiarities in tubulin polymorphism are considered.


Antioxidant and immunoregulatory activity of Ganoderma lucidum polysaccharide (GLP).
Four polysaccharides (GLP-I, GLP-II, GLP-III and GLP-IV) were obtained from fermented soybean curd residue by Ganoderma lucidum, and then purified using anion-exchange DEAE Sephadex A-50. Their structural characterization was conducted by Fourier transform infrared spectroscopy (FTIR), and their monosaccharide compositions were determined. The results demonstrated that the basic structural characterization of four polysaccharides were similar, however, monosaccharide compositions of four kinds of polysaccharides were significant difference. GLP-III and GLP-IV were composed of six kinds of monosaccharide. Nevertheless, GLP-II was composed of three kinds of monosaccharide. Moreover, their antioxidant activities were investigated on the basis of hydroxyl radical, reducing power, DPPH free radical, chelating activity, ABTS radical-scavenging and SOD-like activity. The results showed that four polysaccharides exhibited antioxidant activities in a concentration-dependent manner. Among four polysaccharides, GLP-III and GLP-IV exhibited the higher scavenging effects on hydroxyl radicals, ABTS radical, DPPH free radical, and stronger reducing power and SOD-like activity than GLP-I and GLP-II. In addition, treatment with 40 μg/mL of GLP showed significant stimulation to the macrophage proliferation and higher nitric oxide production. Overall, GLP from fermented SCR could have potential applications in the medical and food industries.


Death in a country area and its effect on the health of relatives.
The histories of the persons dying in a country district during 1973 were examined. The number of visits to the doctors, and also the days spent in hospital by their close relatives in the two years before 1973 were compared with those in the two years that followed. A control group was also examined. There were significant differences in these figures. Analysis suggests that ill health in those aged 50 and over increases after the death of a close relative. A group which is "at risk" after bereavement appears to have been identified.


A Population-Based Cohort Study Examining the Long-term Risk of Repeated Surgery in Non-Helicobacter pylori-Infected PPU Patients Who Underwent Simple Closure.
The management of perforated peptic ulcer (PPU) has shifted from vagotomy/drainage to simple closure, followed by postoperative proton pump inhibitors (PPIs) and Helicobacter pylori (HP) eradication. Few studies have focused on the long-term impacts of this trend shift. We hypothesize that simple closure with PPIs is sufficient and does not carry an elevated rate of repeated surgery in non-HP-infected PPU patients. Hospitalized PPU patients who underwent simple closure or truncal vagotomy/pyloroplasty (TVP) in the National Health Insurance Research Database (NHIRD) from 2000 to 2008 were collected. The index date was defined as the date of ulcer admission. Patients who underwent other ulcer surgeries (e.g., gastrectomy, highly or selective vagotomy), who had a history of HP infection, or who were < 18 or > 100 years old were excluded. Additionally, the distributions of postoperative nonsteroidal anti-inflammatory drug (NSAID) and PPI use were calculated using the Longitudinal Health Insurance Database (LHID). After exclusion, a total of 66,413 patients were enrolled. There were 7232 (10.9%) patients who underwent TVP and 59,181 (89.1%) patients who underwent simple closure. The incidences of repeated ulcer-associated surgery were 5.10 and 23.05 versus 5.11 and 15.77 per 1000 person-years in the TVP cohort vs. the simple closure cohort before and after propensity score matching, respectively. When adjusted for age, sex, comorbidity, and Charlson comorbidity index score, the TVP cohort had a 68% (HR) and 66% (sHR) decreased risk compared with the simple closure cohort before propensity score matching, with a 67% decreased risk after propensity score matching in Cox proportional subdistribution hazard analysis and a 66% decreased risk in Fine-Gray proportional subdistribution hazard analysis. The LHID analysis showed a lower rate of postoperative NSAID use and a higher rate of postoperative PPI use in simple closure patients. Our findings suggest that in the Asian population, simple closure increases the risk of repeated ulcer-associated surgery in non-HP-infected PPU patients compared with TVP patients. However, further studies are warranted.


Preterm labor and bacterial intraamniotic infection: arachidonic acid liberation by phospholipase A2 of Fusobacterium nucleatum.
The studies presented in this report were undertaken to evaluate whether Fusobacterium nucleatum, a common anaerobic isolate in intrauterine infection, stimulates arachidonic acid metabolism, a rate-limiting step for prostaglandin synthesis, in the human uterine endometrium. Effects of F nucleatum on arachidonic acid liberation from human uterine endometrial cells and of F nucleatum extract on lysophosphatidylcholine production in human uterine endometrial cells were investigated. When human uterine endometrial cells labeled with tritiated arachidonic acid to an isotopically steady state were exposed to an extract of F nucleatum, arachidonic acid liberation was stimulated, accompanied by lysophospholipid formation. Similar stimulatory effects on phospholipid degradation were also observed in the experiment with bacterially conditioned media. These results suggest that F nucleatum stimulates endometrial phospholipid metabolism, related to activity of phospholipase A2, which might induce the onset of labor associated with intraamniotic infection.


Polyubiquitin recognition by AtSAP5, an A20-type zinc finger containing protein from Arabidopsis thaliana.
Stress associated proteins (SAPs) in plants contain A20-type zinc finger (A20_ZF) domains and are involved with abiotic stress response. A20-type zinc finger domains in animals reportedly recognize ubiquitin as a regulatory signal in cell. However, it remains unclear whether A20_ZF domains in plants perform similar roles. AtSAP5, a SAP from Arabidopsis thaliana, exhibits a unique sequence feature among 10 AtSAPs harboring A20_ZF domains. The highly conserved diaromatic patch is replaced by the dialipathic patch. Here we investigated whether AtSAP5 recognizes ubiquitin and the roles of the dialipathic patch in ubiquitin binding in vitro. GST pulldown assay reveals that AtSAP5 binds polyubiquitin rather than monoubiquitin. AtSAP5 shows preferences for linear and K63-linked polyubiquitin chains to K48-linked one. The A20_ZF domain of AtSAP5 is sufficient for linkage-specific polyubiquitin recognition. The dialipathic patch in AtSAP5 plays an important role in K48-linked polyubiquitin recognition. Taken together, our results suggest that AtSAP5 participates in polyubiquitin recognition in plants and that the dialipathic patch in AtSAP5 is critical in binding K48-linked polyubiquitn chains.


Atomic force microscopy to characterize the molecular size of prion protein.
The conformational transition of alpha-helix-rich cellular prion protein (PrP(C)) to an isomer with high beta-sheet content is associated with transmissible spongiform encephalopathies. With the ultimate long-term goal of using imaging techniques to study PrP aggregation, we report the results of initial experiments to determine whether PrP molecules could be visualized as single molecules, and if the observed size corresponded to the calculated size for PrP. The investigation of single molecules, and not those embedded into larger aggregates, was the key in our experimental approach. Using atomic force microscopy (AFM) as an imaging method, the immobilization of recombinant histidine (His)10-tagged PrP on mica was performed in the presence of different heavy metal ions. The addition of Cu2+ resulted in an enhanced PrP immobilization, whereas Ni2+ reduced coverage of the surface by PrP. High-resolution data from dried PrP preparations provided a first approximation to geometrical parameters of PrP precipitates, which indicated that the volume of a single PrP molecule was 30 nm3. Molecular dynamics simulations performed to complement the structural aspects of the AFM investigation yielded a calculated molecular volume of 33 nm3 for PrP. These experimentally observed and theoretically expected values provide basic knowledge for further studies on the size and composition of larger amyloidal PrP aggregates, PrP isoforms or mutants such as PrP molecules without octarepeats.


Prognostic value of Lynch syndrome, BRAFV600E , and RAS mutational status in dMMR/MSI-H metastatic colorectal cancer in a pooled analysis of Dutch and French cohorts.
Current knowledge on prognostic biomarkers (especially BRAFV600E /RAS mutations) in metastatic colorectal cancer (mCRC) is mainly based on mCRC patients with proficient mismatch repair (pMMR) tumors. It is uncertain whether these biomarkers have the same prognostic value in mCRC patients with deficient mismatch repair (dMMR) tumors. This observational cohort study combined a population-based Dutch cohort (2014-2019) and a large French multicenter cohort (2007-2017). All mCRC patients with a histologically proven dMMR tumor were included. In our real-world data cohort of 707 dMMR mCRC patients, 438 patients were treated with first-line palliative systemic chemotherapy. Mean age of first-line treated patients was 61.9 years, 49% were male, and 40% had Lynch syndrome. BRAFV600E mutation was present in 47% of tumors and 30% harbored a RAS mutation. Multivariable regression analysis on OS showed significant hazard rates (HR) for known prognostic factors as age and performance status, however showed no significance for Lynch syndrome (HR: 1.07, 95% CI: 0.66-1.72), BRAFV600E mutational status (HR: 1.02, 95% CI: 0.67-1.54), and RAS mutational status (HR: 1.01, 95% CI: 0.64-1.59), with similar results for PFS. BRAFV600E and RAS mutational status are not associated with prognosis in dMMR mCRC patients, in contrast to pMMR mCRC patients. Lynch syndrome is also not an independent prognostic factor for survival. These findings underline that prognostic factors of patients with dMMR mCRC are different of those with pMMR, which could be taken into consideration when prognosis is used for clinical decision-making in dMMR mCRC patients and underline the complex heterogeneity of mCRC.


Structural characterization and lipid composition of acquired cholesteatoma: a comparative study with normal skin.
The goal of this work is to characterize the morphology and lipid composition of acquired cholesteatoma. We hypothesize that constitutive lipid membranes are present in the cholesteatoma and resemble those found in human skin stratum corneum. We performed a comparative noninvasive structural and lipid compositional study of acquired cholesteatoma and control human skin using multiphoton excitation fluorescence microscopy-related techniques and high-performance thin-layer chromatography. The structural arrangement of the cholesteatoma is morphologically invariant along a depth of more than 200 μm and resembles the stratum corneum of hyperorthokeratotic skin. Lipid compositional analyses of the cholesteatoma show the presence of all major lipid classes found in normal skin stratum corneum (ceramides, long chain fatty acids, and cholesterol). Consistent with this, evaluation of Nile red and LAURDAN generalized polarization function images of the cholesteatoma show intercellular regions similar to normal skin stratum corneum in terms of lipid membrane packing and local water content. The investigations show the presence of an extremely thickened stratum corneum within the cholesteatoma. The lipid composition and extracellular membranes similar to those of normal skin stratum corneum are present, indicating that a defensive/permeability barrier is present in the cholesteatoma. Finally, it is demonstrated that multiphoton excitation fluorescence microscopy is a suitable noninvasive tool for investigating the morphology and intrinsic physical properties of acquired cholesteatoma.


Severe hypoglycaemia in adults presenting to a hospital emergency department: Clinical characteristics, comorbidities, and mortality outcomes.
To determine the clinical characteristics, risk factors and mortality outcomes associated with severe hypoglycaemia (SH) treated at a hospital emergency department. Adult patients presenting with SH to the Northern General Hospital, Sheffield, UK over a 44-month period were assessed for clinical characteristics, coexisting comorbidities and mortality outcomes, including cause of death, and analysed by age of diabetes onset, below and above age 40 years. Factors that predicted mortality were determined. A total of 619 episodes of SH occurred in 506 individuals. Most had type 1 (T1D; n = 172 [34.0%]) or type 2 diabetes (T2D; n = 216 [42.7%]), but several attendees did not have diabetes (non-DM; n = 110 [21.7%]). Irrespective of age of diabetes onset, patients with T2D had more socioeconomic deprivation and comorbidities (P < 0.005). SH was uncommon in those with young-onset T2D, who constituted 7.2% of all episodes in diabetes. Hospital admission was high (60%-75%). The T2D cohort had the longest inpatient stay (median 5 days, vs. 2 and 3 days for the T1D and non-DM cohorts, respectively). Survival after the index SH episode was lower and mortality was higher in the non-DM (39.1%) and T2D (38.0%) cohorts than the T1D cohort (13.3%; all P < 0.05), with a median time to death of 13, 113 and 465 days, respectively. Most deaths (78%-86%) were from non-cardiovascular causes. Charlson index predicted mortality and poor survival in T1D and T2D (both P < 0.05). Severe hypoglycaemia requiring emergency hospital treatment is associated with non-cardiovascular deaths and exerts a disproportionately greater impact on mortality in people with T2D and those without diabetes. Multimorbidity is an important risk factor for SH and increases mortality risk.


Inhibition of lysine-specific demethylase 1A suppresses neointimal hyperplasia by targeting bone morphogenetic protein 2 and mediating vascular smooth muscle cell phenotype.
Vascular disorders are associated with phenotypical switching of vascular smooth muscle cells (VSMCs). We investigated the effect of bone morphogenetic protein (BMP)-2 in controlling VSMC phenotype and vascular disorder progression. Lysine (K)-specific demethylase 1A (KDM1A) has been identified to target BMP-2 and is employed as a therapeutic means of regulating BMP-2 expression in VSMCs. VSMCs were stimulated with angiotensin II, and the expression of KDM1A and BMP-2 was detected. VSMC proliferation, apoptosis, and phenotype were evaluated. An in vivo aortic injury model was established, and VSMC behaviour was evaluated by the expression of key markers. The activation of BMP-2-associated signalling pathways was examined. We confirmed the inhibitory effect of KDM1A on BMP-2 activity and demonstrated that KDM1A inhibition prevented VSMC transformation from a contractile to synthetic phenotype. In angiotensin II-treated VSMCs, KDM1A inhibition triggered a decrease in cell proliferation and inflammatory response. In vivo, KDM1A inhibition alleviated post-surgery neointimal formation and collagen deposition, preventing VSMCs from switching into a synthetic phenotype and suppressing disease onset. These processes were mediated by BMP-2 through canonical small mothers against decapentaplegic signalling, which was associated with the activation of BMP receptors 1A and 1B. The regulatory correlation between KDM1A and BMP-2 offers insights into vascular remodelling and VSMC phenotypic modulation. The reported findings contribute to the development of innovative strategies against vascular disorders.


An intercellular adhesion molecule-3 (ICAM-3) -grabbing nonintegrin (DC-SIGN) efficiently blocks HIV viral budding.
Efficient inhibition of the HIV infection life cycle at the stages of viral infection, reverse transcription, and post-translational processing has been extensively studied. However, efficient inhibition of HIV assembly and budding has not been reported. Here, we report that dendritic cell-specific intercellular adhesion molecule-3 (ICAM-3) -grabbing nonintegrin (DC-SIGN) and its related protein, DC-SIGNR, effectively block HIV budding from infected cells. Cotransfection of DC-SIGN or DC-SIGNR with HIV demonstrated 95-99.5% inhibition of viral production from host cells. DC-SIGN or DC-SIGNR can also effectively inhibit 90-95% of HIV generation from infected cells. DC-SIGN efficiently reduces the amount of gp120 present on the cell plasma membrane, and completely strips off gp120 from the virions produced by the host cells, suggesting that blockage of HIV budding is due to internalization of gp120 by DC-SIGN.


Molecular steps of cell suicide: an insight into immune senescence.
The cellular and molecular basis of immune senescence is unclear. A number of mechanisms have been proposed. In this issue of the Journal of Clinical Immunology, some of the mechanisms for various immunologic abnormalities in aging are presented. In this article, various molecular steps of both death receptor and mitochondrial pathways of apoptosis in general are reviewed. In particular, the role of apoptosis in T-cell immune senescence is discussed.


Structural organization of the transfer RNA operon I of Vibrio cholerae: differences between classical and El Tor strains.
Nine major transfer RNA (tRNA) gene clusters were analysed in various Vibrio cholerae strains. Of these, only the tRNA operon I was found to differ significantly in V. cholerae classical (sixth pandemic) and El Tor (seventh pandemic) strains. Amongst the sixteen tRNA genes contained in this operon, genes for tRNA Gln3 (CAA) and tRNA Leu6 (CUA) were absent in classical strains as compared to El Tor strains. The observation strongly supported the view that the above two pandemic strains constitute two different clones.


[Novelty and sophistication in palliative care].
The author describes a seven-bed unit set up to care for terminally-ill patients. She discusses the hopes of care team members, and the need for creativity and flexibility in their interventions. Examples of interventions are included.


Management of tracheal wall resection for thyroid carcinoma by tracheocutaneous fenestration and delayed closure using auricular cartilage.
In the case of advanced thyroid carcinoma invading the trachea, surgical procedures for tracheal resection are selected in relation to the degree of invasion. We created a tracheocutaneous fenestration that was later closed with a free auricular cartilage autograft. We present a simple and effective method for permanent closure of tracheostoma. The surgical procedure for delayed closure consists of three steps: (1) preparing the hinge flap with additional undermining of the subcutaneous layer and the strap muscles; (2) removing a portion of the conchal cartilage from the auricle, which is easily performed with a semicircular skin incision along the anthelix of the ear; and (3) placing the conchal cartilage with its convex surface upward just over the sutured hinge flap layer. Under local anesthesia, we successfully employed this reconstructive procedure for 5 patients. Unfortunately, however, in one patient, we had to reopen the closed tracheocutaneous fenestration on the second postoperative day because of an acute problem that was independent of the closure surgery. Four patients remain in satisfactory condition for more than 2 years since the closure of tracheostoma. The auricular cartilage free graft is a relatively simple procedure which supplies tracheal wall skeletal support for the permanent closure of the tracheocutaneous fenestration.


Creating hierarchical models of protein families based on Expressed Sequence Tags: the "Sprockets" analysis pipeline.
We have created an analysis pipeline called Sprockets, which can be used to classify proteins into various hierarchical "families", and build searchable models of these families. The construction of these families is based on data from Expressed Sequence Tags (ESTs) and Coding DNA Sequences (CDSs), making Sprockets clusters especially suitable for studying gene families in organisms for which the completely sequenced genome does not (yet) exist. The pipeline consists of two main parts: pair-wise analysis and grouping of sequences with Z-score statistics, followed by hierarchical splitting of clusters into alignable protein families. Various computational and statistical techniques applied in Sprockets allow it to act like a massive and selective multiple sequence alignment engine for combining individual sequence collections and related public sequences. The end result is a database of gene Hidden Markov Models, each related to the other by three levels of similarity: secondary structure, function and evolutionary origin. For a sample 20,000 EST set from Lactuca spp., Sprockets provided a 9% improvement in mapping of function to unknown sequences over traditional pair-wise search methods and InterPro mapping.


Tricuspid regurgitation in patients with acquired, chronic, pure mitral regurgitation. II. Nonoperative management, tricuspid valve annuloplasty, and tricuspid valve replacement.
The incidence, preoperative and intraoperative diagnosis, methods, and the clinical and hemodynamic features of patients with and without tricuspid regurgitation associated with chronic mitral regurgitation were presented in Part I. This study (Part II) compares the early and late results in patients with chronic, pure mitral regurgitation undergoing isolated mitral valve replacement, mitral replacement and tricuspid valve annuloplasty, and mitral and tricuspid valve replacement. The mean follow-up interval was 6 years. Those with the longest duration of symptoms (18 years) required tricuspid and mitral valve replacement (11 patients), whereas those with the shortest duration (8.1 years) had only mitral replacement (22 patients). Eight patients had minimal tricuspid regurgitation by digital palpitation, with no procedure performed, and six had tricuspid valve annuloplasty, only one of whom received a ring support. Operative mortality rate was similar in all groups (13% to 18%). All but two of the surviving patients improved by at least one New York Heart Association functional class, and no statistically significant differences were found between preoperative and postoperative hemodynamic data. There were no statistically significant differences in survival at 1, 5, or 8 years (85%, 70%, and 60%, respectively) for patients with or without TR. Only two of the surviving five patients who underwent tricuspid valve annuloplasty were alive 3 years after operation, whereas 70% to 80% of those with mitral replacement or mitral and tricuspid replacement were alive after the same time interval. It is not clear whether or not the pathogenesis of tricuspid regurgitation resulting from mitral regurgitation is different from that of tricuspid regurgitation resulting from mitral stenosis. It is our contention that whether tricuspid regurgitation arises because of anatomic destruction of the tricuspid valve or because of right ventricular dilatation with tricuspid annular enlargement, the underlying mitral valve lesion may determine the preoperative and postoperative courses of these patients. Therefore, when tricuspid valve disease is being evaluated, we urge that patients be categorized by the nature of their underlying mitral or aortic valve lesions.


Physical frailty and decline in general and specific cognitive abilities: the Lothian Birth Cohort 1936.
Physical frailty is associated with many adverse outcomes including disability, chronic disease, hospitalisation, institutionalisation and death. It is unclear what impact it might have on the rate of normal cognitive ageing. We investigated whether physical frailty was related to initial level of, and change in, cognitive abilities from age 70 to 79 years. Participants were 950 members of the Lothian Birth Cohort 1936. Physical frailty was assessed at age 70 years using the Fried criteria. Cognitive function was assessed at ages 70, 73, 76 and 79 years. We used linear regression to examine cross-sectional and prospective associations between physical frailty status at age 70 years and factor score estimates for baseline level of and change in four cognitive domains (visuospatial ability, memory, processing speed and crystallised ability) and in general cognitive ability. Physical frailty, but not prefrailty, was associated with lower baseline levels of visuospatial ability, memory, processing speed and general cognitive ability after control for age, sex, education, depressive symptoms, smoking and number of chronic illnesses. Physical frailty was associated with greater decline in each cognitive domain: age-adjusted and sex-adjusted standardised regression coefficients (95% CIs) were: -0.45 (-0.70 to -0.20) for visuospatial ability, -0.32 (-0.56 to -0.07) for memory, -0.47 (-0.72 to -0.22) for processing speed, -0.43 (-0.68 to -0.18) for crystallised ability and -0.45 (-0.70 to -0.21) for general cognitive ability. These associations were only slightly attenuated after additional control for other covariates. Physical frailty may be an important indicator of age-related decline across multiple cognitive domains.


Separation of human globin chains by micellar electrokinetic capillary chromatography.
A new separation method of human globin chains by micellar electrokinetic capillary chromatography (MECC) is described. In this method, a 25 mM phosphate buffer (pH 2.5) containing 7 M urea and 1% (w/v) reduced Triton X-100 buffer system was used. All experiments were performed in a 47 cmx50 microm I.D. uncoated fused-silica capillary. The separation voltage was set at 19 kV. Normal globin chains derived from normal adults and newborns, alpha, beta, delta, Ggamma and Agamma globin chains as well as common variant globin chains were successfully separated within 20 min. High reproducible migration times of globin chains (CVs of intra- and inter-assay were less than 1% and 2% respectively), and quantification of Ggamma and Agamma chains (CVs for intra- and inter-assay were less than 5% and 10%, respectively) were obtained. This new MECC method provides primary information on structural modification of globin chains. It can be an important diagnostic tool in clinical laboratory practice in the field of hemoglobinopathies.


Enrichment of bovine X-sperm using microfluidic dielectrophoretic chip: A proof-of- concept study.
The microfluidic dielectrophoretic (MF-DEP) chip is a new, economical and readily-available technology that might be used to enrich X-sperm for increasing female offspring in dairy farms. In this study, we sought to develop an MF-DEP chip to enrich X bovine sperm. The MF-DEP chip was composed of an electrode attached to a glass slide and a microchannel made from polydimethylsiloxane. Sex-sorted sperm from flow cytometry were used to identify optimal electric field conditions while unsorted sperm were later tested for sorting efficiency. The results show that during dielectrophoresis some sperm attached to the electrode (called positive DEP; pDEP) whereas other moved away from the electrode (called negative DEP; nDEP). X and Y-sperm responded to dielectrophoresis differently depending on various factors such as buffers, voltages, and frequencies. We found that the condition 4 V 1 MHz significantly reduced (P < 0.05) the percentage of Y-sperm to nearly 30 and therefore enriched X-sperm. The sorting efficiency was dependent on buffer, bull, sorting cycle, flow rate, electrical voltage, and frequency. Notably, the best sorting buffer found in this experiment was the conducting buffer, but this buffer significantly reduced sperm viability and motility. Other sperm-friendly buffers, TRIS and mHTF, were also used, but could not enrich X-sperm. In conclusion, this is a proof of concept that the MF-DEP chip can be effectively used to enrich bovine X-sperm. However, more research must be performed particularly to find the best sorting buffer to effectively sex-sort sperm while providing high motility and sperm viability.


Introduce an optimal method of ovarian stimulation in the polycystic ovarian syndrome affected: a randomized controlled trial.
Currently, optimal method of ovarian stimulation (OS) to in-vitro fertilization (IVF) in the patients with polycystic ovarian syndrome (PCOS) is unknown. The present research aims to study the efficiency of minimal-OS method in treatment of infertile patients with PCOS and also the effect of gonadotropin type (recombinant FSH (r-FSH) vs. urinary Human menopausal gonadotropin (u-HMG)) on treatment cycles with GnRH-antagonist. In this randomized controlled trial, a total of 120 eligible patients were randomly allocated into four groups of OS to IVF: minimal-OS with r-FSH, minimal-OS with u-HMG, mild-OS with r-FSH and mild-OS with u-HMG. IVF outcomes of groups were analyzed statically. The statistical analysis showed that there were significant differences among groups regarding stimulation duration (p < 0.0001), number of retrieved oocytes (p < 0.0001), number of obtained embryos (p < 0.0001). There were no statistically significant differences in fertilization rate (p = 0.289) and implantation rate (p = 0.757) among our participants. There were also significant differences among these four groups in terms of clinical pregnancy rate (/ET and /cycles) (p < 0.0001, p = 0.021, respectively) and live birth rate/cycles (p < 0.0001). Also cases of freeze all embryos due to prevention of ovarian hyper stimulation syndrome (OHSS) (p = 0.004). On the basis of present results the minimal-OS with u-HMG may be one of optimal methods of control OS in the patients with PCOS in respect to serum levels of estradiol on the day of triggering final oocyte maturation, total dose of prescribed gonadotropin, the optimal number of oocytes and embryos obtained, rate of clinical pregnancy and the incidence of OHSS risk. NCT, NCT03876145. Registered 15/03/2019. Retrospectively registered, http://www. gov/ NCT03876145.


Primary hyperparathyroidism: changes on biochemical and hormonal profile related to pregnancy.
A woman with mild asymptomatic hypercalcemia due to primary hyperparathyroidism became pregnant and her serum calcium normalized while her hypophosphatemia worsered. The PTH was low normal, but her urinary cAMP was elevated. In the second trimester of pregnancy a parathyroid adenoma was removed. After surgery, a transient hypocalcemia that normalized ten days later, a partial recovery of hypophosphatemia, and a 40% reduction of the elevated urinary cAMP excretion were observed. Pregnancy continued uneventful and a normal newborn was delivered. This case demonstrates the diagnostic difficulties posed by primary hyperparathyroidism during pregnancy, derived from inapparent changes in serum calcium and PTH. However, phosphorus and urinary cAMP deviations are significant constituting the basis for a correct diagnosis.


Juvenile stress leads to long-term immunological metaplasticity-like effects on inflammatory responses in adulthood.
Previous studies indicate that individuals exposed to stress in juvenility are more prone to suffer from stress-related psychopathologies in adulthood. Evidence suggests that exposure to enriched environment (EE) conditions alleviates juvenile stress (JVS) effects. Exposure to stress has been found to affect immune responses to challenges, but whether JVS has long-term effects on inflammatory processes remains unclear. Here, we examined the impact of JVS on inflammatory processes in adulthood, and the effects of exposure to EE conditions. Adult rats exposed to JVS showed elevated levels of blood monocytes after induction of peritoneal inflammation. This was associated with higher concentration of blood chemokine ligand type 2 (CCL2), but lower levels of its receptor, chemokine receptor type 2 (CCR2) on these monocytes, indicating reduced ability of these monocytes to be recruited to the inflammatory site. In accordance, JVS led to reduced levels of recruited macrophages at the peritoneal cavity, as well as a reduced activation ratio for the release of peritoneal interleukin-10 (IL-10) by lipopolysaccharide (LPS) activation. EE conditions, which fully reversed the anxiety-like behavior resulting from exposure to JVS, did not reverse JVS-induced alterations in blood concentration of monocytes or peritoneal macrophages, but affected IL-10 activation ratio. This effect was associated with a compensatory elevation of the peritoneal CCL2-CCR2 axis. Our results demonstrate long-term metaplasticity-like effects of JVS, which alter inflammatory processes in response to immune challenges in adulthood. Our results also raise the possibility that EE does not simply reverse the effects of JVS but rather indirectly modulates its impact.


Octapeptide repeat alteration mutations of the prion protein gene in clinically diagnosed Alzheimer's disease and frontotemporal dementia.
Studies focusing on octapeptide repeat alteration mutations in PRNP in Alzheimer's disease (AD) and frontotemporal dementia (FTD) cohorts have been rare. We aim to screen sporadic AD and FTD patients with unknown etiology for the octapeptide repeat insertions and deletions in PRNP. Two hundred and six individuals were screened for alterations to the repeat region in the PRNP gene, including 146 sporadic AD and 60 sporadic FTD patients. Our study showed a 1.5% (3/206) occurrence of the octapeptide repeat alteration mutations in PRNP in a Chinese cohort of sporadic dementia. One late-onset FTD patient and one early-onset AD patient each had a two-octapeptide repeat deletion in PRNP, while one early-onset AD patient had a five-octapeptide repeat insertion mutation. PRNP octapeptide repeat alteration mutations are present in sporadic AD and FTD patients. The genetic investigation for PRNP octapeptide repeat alteration mutations in sporadic dementia patients should be carried out in future clinical studies.


[Post-transfusion hemolysis in premature infants. Apropos of 8 cases of post-transfusion hemolysis in premature infants].
Accidents related to blood transfusion have become rare in neonates, due to the application of very strict rules. The 8 reported cases of post-transfusion hemolysis occurred in prematures less than 32 weeks gestational age. Signs consisted of hemoglobinuria and/or severe jaundice. In some patients exchange-transfusion had to be performed. Immuno-hematologic, bacteriologic and technical investigations did not show the etiology of these accidents. No similar clinical reports were found in the literature. Some authors suggest a mechanical origin.


Chicken anemia virus strains with a mutated enhancer/promoter region share reduced virus spread and cytopathogenicity.
Plasmid pCAV/E contains an infectious cloned double-stranded CAV (chicken anemia virus) DNA genome (Noteborn et al., J. Virol. 65 (1991) 3131-3139). We have constructed mutated CAV genomes by introducing mutations into the CAV promoter/enhancer region of pCAV/E. Various mutated CAV strains were functional and had a smaller cytopathogenic effect in chicken T cells than wild-type CAV. In particular, mutations within the '12-bp insert' of the promoter/enhancer region had this effect. PCR and sequence analysis showed that the CAV mutants were stable under cell-culture conditions. Southern-blot analysis showed that all replication DNA intermediates were normally formed by the CAV mutants. All viable mutant CAV strains were able to produce a neutralizing conformational epitope, which implies that they can trigger the required protective immune response. These features make these mutant CAV strains potential candidates for the development of an attenuated CAV vaccine.


Family caregivers require mental health specialists for end-of-life psychosocial problems at home: a nationwide survey in Japan.
Psychological distress is problematic for patients and their family caregivers in the oncological setting. The level of stress is influenced by the health status of the patient and their family members as well as the support system for home care. However, it remains unclear how best to support distressed caregivers providing end-of-life care at home. The present study was performed as part of the Japan Hospice and Palliative Care Evaluation study among caregivers whose family members are provided home palliative care. The caregivers were asked whether they wished to receive psychological support from mental health specialists, and factors associated with the need for psychological support were analyzed. Of the 1052 caregivers, 628 completed the questionnaire. As a whole, 169 subjects [27%; 23-30% (95% confidence interval)] reported needing psychological support from a mental health specialist. According to a multiple regression analysis, factors associated with the need for psychological support included (1) emotional distress due to the need to adapt to rapid worsening of the patient's condition [adjusted odds ratio: 2.62 (95% CI 1.77-3.88), p < 0.001], (2) the poor health conditions of the caregivers [2.93 (1.61-5.36), p < 0.001], and (3) having someone else available to care for the patient in place of the caregiver [0.51 (0.34-0.78), p = 0.002]. Psychological support is required for caregivers tending to patients at home. Further studies are needed to construct a system to provide continuous support to caregivers. Copyright © 2015 John Wiley & Sons, Ltd.


Resection of the liver in a metastatic disease caused by renal carcinoma.
Two patients are presented who had their livers resected because of the metastasis of the kidney tumour. It is a contribution in the discussion on the possibility of treatment of a well-advanced cancer disease. The treatment chosen was possible because of the close co-operation between two different teams of surgeons.


Improved method of injecting local anesthetic solutions for breast operations.
An improved method of injecting local anesthetic solutions for gynecomastia operations and augmentation mammaplasties is described.


Exercise Promotes Tissue Regeneration: Mechanisms Involved and Therapeutic Scope.
Exercise has well-recognized beneficial effects on the whole body. Previous studies suggest that exercise could promote tissue regeneration and repair in various organs. In this review, we have summarized the major effects of exercise on tissue regeneration primarily mediated by stem cells and progenitor cells in skeletal muscle, nervous system, and vascular system. The protective function of exercise-induced stem cell activation under pathological conditions and aging in different organs have also been discussed in detail. Moreover, we have described the primary molecular mechanisms involved in exercise-induced tissue regeneration, including the roles of growth factors, signaling pathways, oxidative stress, metabolic factors, and non-coding RNAs. We have also summarized therapeutic approaches that target crucial signaling pathways and molecules responsible for exercise-induced tissue regeneration, such as IGF1, PI3K, and microRNAs. Collectively, the comprehensive understanding of exercise-induced tissue regeneration will facilitate the discovery of novel drug targets and therapeutic strategies.


Secondary tracheoesophageal puncture with a flexible transillumination device: a new technique and its outcomes.
This study aims to describe a new secondary tracheoesophageal puncture technique with voice prosthesis insertion under local anesthesia with a low-cost device and evaluate its outcome. With a transoral flexible transillumination device of aluminum of 2.3 mm with fiberoptic light, the esophagus's anterior wall is visualized through the tracheostomy. A tracheoesophageal fistula is made with a blade and passed through the fistula. Then a bent trocar is introduced into the lumen using the device as a guidewire. Once in the lumen, a thin guide wire is passed through up to the mouth. The voice prosthesis is positioned with retrograde insertion. Then, the patient is discharged without hospitalization. 15 patients submitted to this technique had a successful surgical outcome. There were no complications as pneumothorax, esophageal perforation, bleeding, or hospitalization. The new device is feasible under local anesthesia.


Long-term stable production of monocyte-colony inhibition factor (M-CIF) from CHO microcarrier perfusion cultures.
Monocyte-colony inhibition factor (M-CIF) was produced in microcarrier perfusion cultures from engineered Chinese hamster ovary (CHO) cells. Three and fifteen liter microcarrier perfusion bioreactors equipped with internal spin filters were operated for over two months. Approximately 60 L and 300 L of culture filtrate were harvested from the 3L and 15L microcarrier perfusion bioreactors respectively. During the perfusion operation, cell density reached 2-6 × 10(6) cells/ml. Importantly, stable expression of M-CIF from the CHO cells under non-selection condition was maintained at a level of 4-10 mg/L. Specific productivity was maintained at 1.8-3.4 mg/billion cells/day. The ability of the recombinant CHO cells to migrate from microcarrier to microcarrier under our proprietary HGS-CHO-3 medium greatly facilitated microcarrier culture scale-up and microcarrier replenishment. Future directions for microcarrier perfusion system scale-up and process development are highlighted.


Model-assisted Design of Experiments as a concept for knowledge-based bioprocess development.
Design of Experiments methods offer systematic tools for bioprocess development in Quality by Design, but their major drawback is the user-defined choice of factor boundary values. This can lead to several iterative rounds of time-consuming and costly experiments. In this study, a model-assisted Design of Experiments concept is introduced for the knowledge-based reduction of boundary values. First, the parameters of a mathematical process model are estimated. Second, the investigated factor combinations are simulated instead of experimentally derived and a constraint-based evaluation and optimization of the experimental space can be performed. The concept is discussed for the optimization of an antibody-producing Chinese hamster ovary batch and bolus fed-batch process. The same optimal process strategies were found if comparing the model-assisted Design of Experiments (4 experiments each) and traditional Design of Experiments (16 experiments for batch and 29 experiments for fed-batch). This approach significantly reduces the number of experiments needed for knowledge-based bioprocess development.


First transcriptome of the copepod Gladioferens pectinatus subjected to chronic contaminant exposures.
Contaminants are often at low concentrations in ecosystems and their effects on exposed organisms can occur over long periods of time and across multiple generations. Alterations to subcellular mechanistic pathways in response to exposure to contaminants can provide insights into mechanisms of toxicity that methods measuring higher levels of biological may miss. Analysis of the whole transcriptome can identify novel mechanisms of action leading to impacts in exposed biota. The aim of this study was to characterise how exposures to copper, benzophenone and diclofenac across multiple generations altered molecular expression pathways in the marine copepod Gladioferens pectinatus. Results of the study demonstrated differential gene expression was observed in cultures exposure to diclofenac (569), copper (449) and benzophenone (59). Pathways linked to stress, growth, cellular and metabolic processes were altered by exposure to all three contaminants with genes associated with oxidative stress and xenobiotic regulation also impacted. Protein kinase functioning, cytochrome P450, transcription, skeletal muscle contraction/relaxation, mitochondrial phosphate translocator, protein synthesis and mitochondrial methylation were all differentially expressed with all three chemicals. The results of the study also suggested that using dimethyl sulfoxide as a dispersant influenced the transcriptome and future research may want to investigate it's use in molecular studies. Data generated in this study provides a first look at transcriptomic response of G. pectinatus exposed to contaminants across multiple generations, future research is needed to validate the identified biomarkers and link these results to apical responses such as population growth to demonstrate the predictive capacity of molecular tools.


Hepatitis B virus infection in immigrants to the southern Brazilian Amazon.
To identify epidemiological patterns and risk factors associated with hepatitis B virus (HBV) infection in the southern Brazilian Amazon, a survey was performed in the county of Terra Nova do Norte in the northern part of the state of Mato Grosso. The population consists mainly of immigrants from the southern part of Brazil, where HBV prevalence is low. A random sample (n = 783) of the population was interviewed and tested for HBV markers. The overall prevalence of HBV infection was 54.7%. There were 31 hepatitis B surface antigen (HBsAg) carriers (3.9%), with a low rate of HBV e antigen positivity, and none with anti-hepatitis D virus. Subtypes ayw3 and ayw2 of HBsAg were predominant, suggesting that the immigrants carried HBV from their original region to the Amazon. Clustering of HBV infection within families was found. The association between HBV markers and having lived in a gold-miners' camp, even after adjusting for confounders, indicated that the gold-miners may play a role in HBV spread in areas of the Amazon where gold prospecting occurs.


Evaluation of a patient with central retinal vein occlusion.
Patients suffering a central retinal vein occlusion should be evaluated for conditions that promote and/or contribute to the formation of a thrombosis in the central retinal vein. These conditions include alterations of blood flow, altered viscosity of the blood, abnormalities of coagulation, and abnormalities of vessel walls. Patients with either a partial or complete central retinal vein occlusion have similarities in the age of onset, associated systemic findings, and laboratory data. At the time of onset, 90% of patients are older than 50 years. Seventy-four percent of patients will have symptoms or signs of associated systemic vascular disease (ie, hypertension, arteriosclerotic heart disease, and diabetes mellitus.) The most common laboratory findings include elevated blood lipids, abnormalities of glucose tolerance testing, and abnormalities of protein chemistries. Evaluation should include both a complete ocular and medical examination with appropriate laboratory tests and special studies. Assessment of central retinal venous pressure may be helpful in identifying those patients who have a severe, complete thrombosis and are at significant risk to develop anterior segment neovascularization.


The Croonian Lecture 2004 risk: food, fact and fantasy.
We all take risks, but most of the time we do not notice them. We are generally bad at judging the risks we take, and in the end, for some of us, this will prove fatal. Eating, like everything else in life, is not risk free. Is that next mouthful pure pleasure, or will it give you food poisoning? Will it clog your arteries as well as filling your stomach? This lecture weaves together three strands-the public understanding of science, the perception of risk and the role of science in informing government policy-as it explains how food risks are assessed and managed by government and explores the boundaries between the responsibilities of the individual and the regulator. In doing so, it draws upon the science of risk assessment as well as our attitudes to risk in relation to issues such as bovine spongiform encephalopathy, dioxins in salmon and diet and obesity.


Radiotherapy management of paediatric cancers with synchronous metastasis.
Cancer in childhood represent 1% of all the new diagnosed cancers. About 30% of children with cancer receive radiation therapy, representing about 600 to 700 patients per year in France. As a consequence, paediatric cancers with synchronous metastasis is a very rare situation in oncology, with usually poor standard of care. However, considerable efforts are made by paediatric oncology scientific societies to offer trials or treatment consensus despite these rare situations. The article proposes to synthesize the radiotherapy management of both primary tumour and synchronous metastasis in the most "common" childhood or adolescent cancers.


Improvement of physical and psychological symptoms after breast reduction.
This study suggests that women who underwent breast reduction showed a significant improvement in both physical and psychological symptoms associated with macromastia and in their overall quality of life, 12 months postoperatively. Comparing pre- with postoperative scores obtained with the Body Dysmorphic Disorder Examination Self-Report (BDDE-SR23), the Short Form-36 Health Survey and the Symptom Inventory Questionnaire, the study objectively proves that breast reduction increases patient's satisfaction with their body image and improves their lives from both a psychological and relational point of view.


Temporal improvement in heart failure survival related to the use of a nurse-directed clinic and recommended pharmacological treatment.
The use of recommended drugs for chronic heart failure (CHF) has been discouragingly low in clinical practice. The aim of this study was to prospectively evaluate to which extent a nurse-directed heart failure clinic could accomplish drug titration with modern heart failure treatments, with focus on beta-blockers. Outcome of drug titration was evaluated for 418 patients referred to the nurse-run clinic from 1995 through 2001, using a prospective, open, non-randomised quality control protocol. Throughout the period, most of the patients were discharged on an ACE inhibitor (during 2001, 86%). The use of beta-blockers increased during the observation (from 43% to 88%). Patients started on an ACE-inhibitor treatment continued in 89% and in 95% when started on a beta-blocker. There was a significant decrease in mortality, relative risk per year 0.84 (95% CI, 0.75 to 0.94), P=0.002. Three-year mortality was reduced from 27% to 10%. In a multivariable analysis, survival was significantly associated with ejection fraction, renal function, the use of beta-blockers and ACE inhibitors, and negatively with digitalis treatment. The nurse-directed titration succeeded in introducing more patients on beta-blockers than on ACE-inhibitors. Mortality was reduced during the study period, associated with more use of documented therapy, beta-blockers in particular. These findings suggest that the observed signs of improvement in CHF prognosis are likely caused by more efficient medical treatment.


A neon-matrix isolation study of the reaction of non-energetic H-atoms with CO molecules at 3 K.
The efficiency of HCO formation stemming from non-energetic H-atoms and CO molecules is highlighted both in the condensed phase and within a neon matrix environment, which is half-way between the condensed-phase and gas-phase. Our experiments demonstrated that HCO production within the neon-matrix needed very little or no activation energy. The efficiency of HCO formation depended only on the capability of H-atoms to diffuse in the solid and to subsequently encounter CO molecules. The novelty of the presented matrix experiment sheds light on the debated question of whether activation energy is required in order to produce HCO, because of the use of non-energetic ground state H-atoms within the neon-matrix.


The anacardic 6-pentadecyl salicylic acid induces macrophage activation via the phosphorylation of ERK1/2, JNK, P38 kinases and NF-κB.
Amphipterygium adstringens is a plant traditionally used to treat gingivitis, gastric ulcer and even gastric cancer but the mechanism involved in the regulation of the immune response is not elucidated yet. The 6-pentadecylsalicylic acid (6SA) is the main anacardic acid found in A. adstringens. In order to evaluate the immune-modulatory abilities of 6SA, we used mouse splenocytes and determined the phosphorylation of the transcription factor NF-κB and MAP kinases ERK1/2, JNK and p38 in helper and cytotoxic T cells, natural killer (NK) cells and F4/80(+) macrophages. Treatment with 6SA was not cytotoxic as measured by both trypan blue exclusion and tetrazolium salts (MTT) tests. Additionally, 6SA did not alter the proportion of helper and cytotoxic T lymphocytes, NK cells or macrophages. Moreover, 6SA treatment significantly increased the phosphorylation of ERK1/2, JNK, P38 and NF-κB mainly in macrophages. In this cells (peritoneal macrophages), treatment with 6SA increased the secretion of nitric oxide (NO), interleukin (IL)-6 and tumour necrosis factor (TNF)-α and decreased the secretion of IL-4 and IL-10 depending on MAPK and NF-κB phosphorylation. In addition, 6SA increased the migration and phagocytic activity of macrophages also depending on the phosphorylation of different kinases. These data suggest that 6SA induces the classical activation pathway in macrophages via the phosphorylation of MAP kinases and NF-κB thus activating the adaptive immune system.


The Ovo/Shavenbaby transcription factor specifies actin remodelling during epidermal differentiation in Drosophila.
In Drosophila, differentiation of the epidermis results in a stereotyped array of cells with F-actin-based extensions at their apical face. We identified Ovo/Shavenbaby (Svb) as a transcription factor that governs changes in epidermal cell shape. Svb is required for the formation of apical extensions and cells deficient in svb differentiate a smooth surface. In both the embryo and the adult, we show that Svb is necessary and sufficient for the cells to grow extensions and that the tight regulation of ovo/svb activity is critical for morphogenesis to occur correctly. We establish that Svb triggers early F-actin redistribution and is able to initiate the entire process of cytoskeletal remodelling, thereby defining it as a major regulator of epidermal differentiation.


Weir Mitchell's 1859 demonstration of "a peculiar contraction" produced by a percussion hammer.
The 1875 publications of Erb and Westphal brought widespread attention to the percussion of muscle stretch reflexes. Although the maneuver may have been observed before 1875, there is little concrete evidence of this. To bring to light an early report of percussion eliciting the muscle stretch response. While studying the Weir Mitchell papers (Philadelphia College of Physicians), the author came across an early report of the maneuver. The 531-word 1859 report, published in the Proceedings of the Academy of Natural Sciences of Philadelphia, was written by a pro tem reporter who observed Mitchell's demonstration of the phenomenon. The other attendees, including Dr. William Hammond, were so well aware of the phenomena that Dr. Mitchell "did not consider it necessary to describe them more fully." Mitchell viewed the response as muscular in nature and the relationship between this response and disease was not explored in the report. This 1859 report preceded the Erb and Westphal publications by nearly two decades. It is perhaps the first concrete proof that neurologists were observing this phenomenon as early as the mid-1800s. Mitchell viewed the phenomenon as a local muscle response. While the concepts that later allowed Erb to correctly interpret the phenomenon as a reflex arc were already in place, Mitchell did not synthesize these concepts.


Association of ATP binding cassette transporter G8 rs4148217 SNP and serum lipid levels in Mulao and Han nationalities.
The association of ATP binding cassette transporter G8 gene (ABCG8) rs4148217 single nucleotide polymorphism (SNP) and serum lipid profiles is still controversial in diverse racial/ethnic groups. Mulao nationality is an isolated minority in China. The aim of this study was to evaluate the association of ABCG8 rs4148217 SNP and several environmental factors with serum lipid levels in the Guangxi Mulao and Han populations. A total of 634 subjects of Mulao nationality and 717 participants of Han nationality were randomly selected from our previous samples. Genotyping of the ABCG8 rs4148217 SNP was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. The genotypic and allelic frequencies of ABCG8 rs4148217 SNP were different between the two nationalities (P < 0.01 for each), the frequency of A allele was higher in Mulao than in Han. The A allele carriers in Han had lower high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (Apo) A1 levels than the A allele noncarriers (P < 0.05 for each), whereas the A allele carriers in Mulao had lower ApoA1 levels than the A allele noncarriers (P < 0.05). Subgroup analyses showed that the A allele carriers in Han had lower HDL-C and higher triglyceride (TG) levels in females but not in males than the A allele noncarriers (P < 0.05 for each), and the A allele carriers in Mulao had lower ApoA1 levels in females but not in males than the A allele noncarriers (P < 0.05). The levels of TG and HDL-C in Han, and ApoA1 in Mulao were associated with genotypes in females but not in males (P < 0.05-0.01). Serum lipid parameters were also correlated with several environmental factors (P < 0.05-0.001). The ABCG8 rs4148217 SNP is associated with serum TG, HDL-C and ApoA1 levels in our study populations, but this association is different between the Mulao and Han populations. There is a sex (female)-specific association in both ethnic groups.


Synergistic effects of combined immunosuppressive modulation. I. Unresponsiveness to dendritic cell-depleted renal allografts in dogs exposed to total-lymphoid irradiation.
Attenuation of the allogeneic stimulus provided by dendritic cells (DC) was achieved by irradiation of the donors, followed by their reconstitution with bone marrow from the prospective DLA-identical recipient. Following long-term (131-187 days) recovery free of graft-versus-host (GVH) disease, the chimeric kidneys were placed into the corresponding recipients; such allografts were rejected at 55, 55, and 60 days, respectively. Four other recipients were conditioned with 1750-1790 cgy of total lymphoid irradiation (TLI) and were then given a similar chimeric kidney from the corresponding partner. These allografts currently survive for 296, 295, 290, and 252 days, respectively. A third group of four dogs was exposed to TLI prior to transplantation of a normal DLA-identical kidney. These grafts were rejected at 20, 42, 46, and 242 days, respectively. Thirteen DLA-identical renal allografts transplanted into normal dogs survived for 13-38 days (mean survival time = 28.6 days). Depletion of allogeneic DC alone, or TLI alone, produced relative prolongations in allograft survival in canine recipients. Combined use of these two modalities, however, resulted in long-term allogeneic unresponsiveness in the recipients.


Racial/Ethnic Residential Segregation, Neighborhood Health Care Provision, and Choice of Pediatric Health Care Provider Across the USA.
Much research has been conducted that demonstrates a link between racial/ethnic residential segregation and health care outcomes. We suggest that minority segregated neighborhoods may have diminished access to organizations and that this differential access may contribute to differences in health care outcomes across communities. We analyze this specifically using the case of pediatric health care provider choice. To examine this association, we estimate a series of multinomial logistic regression models using restricted data with ZIP code level geoidentifiers from the 2011-2012 National Survey of Children's Health (NSCH). We find that racial/ethnic residential segregation is related to a greater reliance on non-ideal forms of health care, such as clinics, and hospital outpatient departments, instead of pediatric physician's offices. This association is at least partially attenuated by the distribution of health care facilities in the local area, physician's offices, and health care practitioners in particular. Additionally, families express greater dissatisfaction with these other forms of care compared to physician's offices, demonstrating that the lack of adequate health care provision is meaningful for health care outcomes. This study expands the literature by examining how the siting of health organizations has consequences for individuals residing within these areas.


[The elbow joint - a diagnostic challenge : anatomy, biomechanics, and pathology].
The elbow is one of the most commonly injured joints in sports activities. In particular, weight lifters, golfers, tennis players, and pitchers are affected. Injuries in sports involving overhead throwing are commonly based on the pathophysiologic model of valgus extension overload syndrome. The injuries are commonly complex and demand a good knowledge of the symptoms, the exact anatomy, and the biomechanics to arrive at a precise radiologic diagnosis. The characteristic patterns of injury that occur in specific sports activities are related to a combination of increased varus or valgus and extension or flexion overload that results in tensile forces and/or compression and shear stress. Acute symptoms are frequently based on chronic degeneration of the tendons and ligamentous structures due to repetitive microtrauma from overuse syndrome.


Emerging functional roles of cathepsin E.
Cathepsin E is an intracellular aspartic protease of the endolysosomal pathway. It has been implicated in several physiological and pathological processes however, its exact functional role is yet to be elucidated. The present review gives an account of the major physiological functions that are associated to cathepsin E by various research groups and highlights the conditions developed in cathepsin E deficiency or the conditions where overexpression of cathepsin E is observed.


Internal defibrillation with minimal skeletal muscle activation: a new paradigm toward painless defibrillation.
Shock-induced pain produces substantial morbidity in recipients of implantable cardioverter-defibrillators (ICDs). This pain likely derives from activation of skeletal muscle and associated nerves in the chest and abdomen. In an effort to develop a painless defibrillation system, we designed an electrode arrangement that incorporates a conductive sock placed around the heart to confine the electric shock field to cardiac tissue. The purpose of this study was to test whether cardiac defibrillation could be achieved without skeletal muscle activation using a novel electrode system. Eight adult mongrel dogs were studied. Force of skeletal muscle contraction was measured by strain gauges attached to the forelimbs during delivery of internal shocks ranging in energy from 0.1 to 31 J. Biphasic shocks were delivered (1) between a right ventricular coil and a subcutaneous dummy can (standard configuration), and (2) between a left ventricular coil and an epicardial electrode sock. Internal and external defibrillation thresholds (DFTs) were determined for each electrode configuration. Shock-induced muscle contraction force was significantly lower using the sock electrode than with standard ICD electrodes at every shock energy level tested (P < .0001). Internal DFT was similar between electrode configurations (sock electrode: 8.6 +/- 4.2 J; standard: 11.0 +/- 6.3 J, P = .4), but muscle contraction force at DFT was greatly reduced with the new electrode system (1.8 +/- 2.0 kg vs 10.6 +/- 2.1 kg, P < .0001). The sock electrode rendered external defibrillation impossible, however, even at 360 J. Skeletal muscle activation induced by ICD shocks can be greatly reduced using an electrode system that confines the electric shock field to the heart. Refinement of this strategy may allow for delivery of painless shocks by ICDs. Further development is needed to overcome implant complexity and the higher external DFT with this type of electrode system.


Novel anti-inflammatory therapy for Parkinson's disease.
Parkinson's disease (PD) is a movement disorder that is characterized by progressive degeneration of the nigrostriatal dopamine system. Although dopamine replacement can alleviate symptoms of the disorder, there is no proven therapy to halt the underlying progressive degeneration of dopamine-containing neurons. Recently, increasing evidence from human and animal studies has suggested that neuroinflammation is an important contributor to the neuronal loss in PD. Moreover, the pro-inflammatory agent lipopolysaccharide itself can directly initiate degeneration of dopamine-containing neurons or combine with other environmental factor(s), such as the pesticide rotenone, to exacerbate such neurodegeneration. These effects provide strong support for the involvement of inflammation in the pathogenesis of PD. Furthermore, growing experimental evidence demonstrates that inhibition of the inflammatory response can, in part, prevent degeneration of nigrostriatal dopamine-containing neurons in several animal models of PD, suggesting that inhibition of inflammation might become a promising therapeutic intervention for PD.


Functional Anatomy of Muscle Mechanisms: Compensating Vertical Heterophoria.
Magnetic resonance imaging (MRI) of extraocular muscle function was used to evaluate the role of newly recognized mechanisms underlying compensation of large heterophoria by vertical fusional vergence (VFV). Prospective case series. At one academic center, 8 adults with large hyperphoria and supernormal VFV underwent MRI during monocular and binocular fixation of a centered, near target. Contractility of the rectus and superior oblique (SO) extraocular muscles in hypertropic and hypotropic eyes was determined from changes in posterior partial volume (PPV). Five of 8 patients could sustain binocular fusion in the scanner. In those patients, VFV corrected approximately 5-degree misalignment, approximately 5-fold greater than normal VFV. Vertical strabismus was compensated mainly by significant contractility of the lateral more than the medial compartment of the inferior rectus (IR) in both eyes (P < .005). The superior rectus (SR) and inferior oblique muscles had no significant contractile contribution, although the hypotropic SO relaxed significantly. The IR lateral compartment and SR medial compartment significantly co-relaxed when binocular fusion was attained from monocular target fixation (P < .01). Although VFV protects patients from small muscle imbalances over the lifespan, even enhanced VFV may be inadequate to avert diplopia. Compensation of hyperphoria by VFV is accomplished mainly by IR muscle relaxation in the hypotropic eye, principally in its selectively innervated lateral compartment, whereas the SO contributes little. Fusion involves compartmentally selective co-relaxation in hypotropic eye vertical rectus muscles. Taken together, these overall findings suggest a physiologic basis to prefer therapeutic surgical weakening of the medial IR in the hypotropic eye.


Starch and protein analysis of wheat bread enriched with phenolics-rich sprouted wheat flour.
Wheat flour in the bread formula was replaced with sprouted wheat flour (SF) characterized by enhanced nutraceutical properties, at 5%, 10%, 15% and 20% levels. The addition of SF slightly increased the total protein content; however, it decreased their digestibility. Some qualitative and quantitative changes in the electrophoretic pattern of proteins were also observed; especially, in the bands corresponding with 27kDa and 15-17kDa proteins. These results were also confirmed by SE-HPLC technique, where a significant increase in the content of proteins and peptides (molecular masses <20kDa) was determined for breads with 20% of SF. Bread enriched with sprouted wheat flour had more resistant starch, but less total starch, compared to control bread. The highest in vitro starch digestibility was determined for the control bread. The studied bread with lowered nutritional value but increased nutritional quality can be used for special groups of consumers (obese, diabetic).


Desire to work from home: Results of an Irish study.
Large levels of working from home (WfH) were induced by social distancing and viral control measures undertaken to mitigate the Covid-19 pandemic. Representing an unpredicted change in the way large amounts of people undertake their day to day work, it is expected that the legacy of this event, in terms of significant alterations to work and commuting patterns will have wide-ranging and long-lasting results. However, how persistent the current trends will be, remains an open question. Therefore, there is a need for a well-represented study of employees' preferences for the post-pandemic future and focus on white-collar workers and their well-established attitudes considering their flexibility in terms of workplace arrangements. This paper presents the results of a survey undertaken in Ireland in the summer of 2021 gauging the desire of office workers to WfH, the format that most appeals to them, the consideration of home relocation based on the ability to WfH, and the factors that may explain such preferences. Results indicate high levels of desire to WfH, either full time or partially, with increased desire to WfH positively correlated to pre-pandemic commute length, and to a perceived increase in work productivity and quality of non-work life as a result of time spent WfH. Additionally, a number of workers state that they may consider home relocation based upon the ability to WfH. These results should be interpreted as the desire to WfH or total addressable market that exists, rather than the likely levels of WfH that will be observed post-Covid.


Ligament, nerve, and blood vessel anatomy of the lateral zone of the lumbar intervertebral foramina.
To provide an anatomical basis for intrusive treatment using an approach through the lateral zones of the lumbar intervertebral foramina (LIF), especially for acupotomology lysis, percutaneous transforaminal endoscopy, and lumbar nerve root block. Blood vessels, ligaments, nerves, and adjacent structures of ten cadavers were exposed through the L1-2 to L5-S1 intervertebral foramina and examined. The lateral zones of the LIF were almost filled by ligaments, nerves, and blood vessels, which were separated into compartments by superior/inferior transforaminal ligaments and corporotransverse superior/inferior ligaments. Two zones relatively lacking in blood vessels and nerves (triangular working zones) were found beside the lamina of the vertebral arch and on the root of the transverse processus. Both the ascending lumbar vein and branches of the intervetebral vein were observed in 12 Kambin's triangles, and in only seven Kambin's triangles were without any veins. Nerves and blood vessels are fixed and protected by transforaminal ligaments and/or corporotransverse ligaments. It is necessary to distinguish the ligaments from nerves using transforaminal endoscopy so that the ligaments can be cut without damaging nerves. Care needs to be taken in intrusive operations because of the veins running through Kambin's triangle. We recommend injecting into the lamina of the vertebral arch and the midpoint between the adjacent roots of the transverse processus when administering nerve root block. Blind percutaneous incision and acupotomology lysis is dangerous in the lateral zones of the LIF, as they are filled with nerves and blood vessels.


Incidence, risk factors, and outcome of portal vein thrombosis after laparoscopic-assisted splenectomy in β-thalassemia patients: a prospective exploratory study.
Portal vein system thrombosis (PVT) is an infrequent but potentially serious complication after laparoscopic splenectomy. Patients with β-thalassemia are at higher risk as they have splenomegaly and hypercoagulability. Forty-eight β-thalassemia patients who underwent hand-assisted laparoscopic splenectomy or laparoscopic splenectomy were studied prospectively with pre- and postoperative Doppler ultrasonography or computed tomography scanning. The incidence of PVT was 8.3% (95% confidence interval [CI] 0.2%-16.4%) (4 of 48 patients). Spleen weight was the only independent factor associated with the presence of PVT. The odds ratio for spleen weight (100 g increase) was 1.46 (95% CI 1.10-1.94, P=.010). Receiver operator characteristic curve analysis showed that the optimal cutoff of spleen weight to the prediction of PVT was 1543 g. Thrombosis resolution was observed after a median of 165 days. Patients with β-thalassemia who undergo laparoscopic-assisted splenectomy are at high risk of postoperative PVT. Close postoperative surveillance and aggressive coagulation prophylaxis are needed in these patients. Larger studies are required to confirm the present findings.


Demonstration of a neurotrophic factor for the maintenance of acetylcholinesterase and butyrylcholinesterase in the preganglionically denervated superior cervical ganglion of the cat.
Under sodium pentobarbital anesthesia, the superior cervical ganglia of cats were preganglionically denervated bilaterally. The following day cats were reanesthetized, the external carotid and lingual arteries were ligated bilaterally, and the right common carotid artery was infused for 24 hr with an extract prepared from cat brain, spinal cord, and sciatic nerves, with and without the incorporation of aprotinin, an inhibitor of proteases. They were sacrificed 48 hr after denervation, and the acetylcholinesterase (acetylcholine acetylhydrolase, EC 126.96.36.199) and butyrylcholinesterase (acylcholine acylhydrolase, EC 188.8.131.52) contents of the superior cervical ganglia were compared with those of similarly denervated control ganglia. Both types of extract produced a significant reduction in the loss of both enzymes from the superior cervical ganglia, as did infusions of aprotinin alone. These findings demonstrate the presence of an endogenous neurotrophic factor for the maintenance of ganglionic acetylcholinesterase and butyrylcholinesterase. Its possible mechanisms of action, and those of aprotinin, are discussed.


Exploration of Binding Affinities of a 3β,6β-Diacetoxy-5α-cholestan-5-ol with Human Serum Albumin: Insights from Synthesis, Characterization, Crystal Structure, Antioxidant and Molecular Docking.
The present study describes the synthesis, characterization, and in vitro molecular interactions of a steroid 3β,6β-diacetoxy-5α-cholestan-5-ol. Through conventional and solid-state methods, a cholestane derivative was successfully synthesized, and a variety of analytical techniques were employed to confirm its identity, including high-resolution mass spectrometry (HRMS), Fourier transforms infrared (FT-IR), nuclear magnetic resonance (NMR), elemental analysis, and X-ray single-crystal diffraction. Optimizing the geometry of the steroid was undertaken using density functional theory (DFT), and the results showed great concordance with the data from the experiments. Fluorescence spectral methods and ultraviolet-vis absorption titration were employed to study the in vitro molecular interaction of the steroid regarding human serum albumin (HSA). The Stern-Volmer, modified Stern-Volmer, and thermodynamic parameters' findings showed that steroids had a significant binding affinity to HSA and were further investigated by molecular docking studies to understand the participation of active amino acids in forming non-bonding interactions with steroids. Fluorescence studies have shown that compound 3 interacts with human serum albumin (HSA) through a static quenching mechanism. The binding affinity of compound 3 for HSA was found to be 3.18 × 104 mol-1, and the Gibbs free energy change (ΔG) for the binding reaction was -9.86 kcal mol-1 at 298 K. This indicates that the binding of compound 3 to HSA is thermodynamically favorable. The thermodynamic parameters as well as the binding score obtained from molecular docking at various Sudlow's sites was -8.2, -8.5, and -8.6 kcal/mol for Sites I, II, and III, respectively, supporting the system's spontaneity. Aside from its structural properties, the steroid demonstrated noteworthy antioxidant activity, as evidenced by its IC50 value of 58.5 μM, which is comparable to that of ascorbic acid. The findings presented here contribute to a better understanding of the pharmacodynamics of steroids.


Semi-quantitative duplex RT-PCR reveals the low occurrence of Porcine Pegivirus and Atypical Porcine Pestivirus in diagnostic samples from the United States.
Porcine Pegivirus (PPgV) and Atypical Porcine Pestivirus (APPV) are two recently identified porcine viruses. In this study, the identification of two viruses by metagenomic sequencing, and a duplex semi-quantitative RT-PCR was developed to detect these pathogens simultaneously. The PPgV strain Minnesota-1/2016 had a 95.5%-96.3% nucleotide identity and clustered with the recently identified US PPgV strains, which is a distant clade from the German PPgV strains. The APPV strain Minnesota-1/2016 shared an 87.3%-92.0% nucleotide identity with the other global APPV strains identity but only shared an 82.8%-83.0% nucleotide identity with clade II consisting of strain identified in China. Detection of both PPgV and APPV was 9.0% of the diagnostic cases. Co-infection of PPgV and APPV was identified in 7.5% of the diagnostic cases. The occurrence and genetic characterization of PPgV and APPV further enhance our knowledge regarding these new pathogens in the United States.


[Temperature dependent alterations of the surface-EMG and ECG: an investigation of the electrical transfer characteristics of the human skin (author's transl)].
The influence of local heating of the skin on the integrated EMG (registered with surface and subcutaneous electrodes), the amplitude of the ECG, the skin blood flow, the electrode impedance, the electrode-to-skin impedance, and the tissue impedance is investigated. Except for the increasing skin blood flow each of the variables exhibits a significant reduction with an increase in skin temperature. From these results the existence of two mechanisms is deduced mediating thermal influence on bioelectric signals picked up by surface electrodes: 1. An alteration of the signal source. 2. An alteration of the electric transfer characteristics of the tissue between signal source and electrode. Especially in quantitative surface electromyography the temperature dependence of the signal can be a source of error.


Strengthened erosion resistance of compacted bentonite by layered double hydroxide: A new electrostatic interaction-based approach.
For the geological repository of high-level radioactive waste (HLW) built in granitic host rock,the control of buffer material (compacted bentonite) erosion and subsequent loss caused by groundwater in granite fissures is an unresolved problem of major concern. We propose here new insight into enhancing the erosion resistance of compacted bentonite by means of its electrostatic interaction with oppositely-charged layered double hydroxide (LDH). The interaction between bentonite and LDH was studied by dropwise addition of colloidal LDH into colloidal bentonite suspension, during which the variation in electrical conductivity, zeta potential and particle size proved a strong interaction between these two materials. Interestingly, in addition to their aggregation, intercalated structures of LDH and montmorillonite were found in the composite (BEN@LDH) by a combined characterization of X-ray diffraction (XRD) and high resolution transmission electron microscopy (HR-TEM), and were confirmed by density functional theory (DFT) calculation. Colloid generation of compacted BEN@LDH under ultrasonic conditions is negligible comparing with that of compacted bentonite, indicating a significantly higher erosion resistance. Besides, a small amount of LDH by mechanically mixing with bentonite (mass ratio 1:99) can also effectively improve the erosion resistance of compacted bentonite. Moreover, BEN@LDH displayed stronger retention performance towards U(VI) and Se(IV) than bentonite under near-neutral/weakly alkaline conditions. Our results indicate that LDH is a promising additive in compacted bentonite, and this approach may be extended to common geotechnical structures built with clays and soils.


Anti-glioma effect and safety of docetaxel-loaded nanoemulsion.
Docetaxel, an inhibitor of microtubule depolymerization, has been used for many malignancies. Due to its toxicity and the non-selective distribution of its commercial formulation, Taxotere®, new formulations with less toxicity and tumor targeting need to be explored. For its safety and ease of factory scale production, nanoemulsion, was selected to encapsulate docetaxel. The particle size of docetaxel loaded nanoemulsion (DNE) was 72.3 nm, the average zeta potential was -6.38 mV, the encapsulation efficiency was 93.1% and the drug loading capacity was 2.87%. Although DNE presented similar antiproliferation effects on both U87 cells and bEnd.3 cells, its in vivo toxicity was significantly lower than Taxotere®. In vivo fluorescent imaging suggested nanoemulsions loaded with a fluorescent probe could distribute to the brain and accumulate at the glioma site. The pharmacological experiments also confirmed that the DNE could target glioma sites and prolong the median survival time of mice with gliomas. In conclusion, DNE is a new, less toxic, drug formulation that is effective for brain glioma therapy.


Brain Organoids: Expanding Our Understanding of Human Development and Disease.
Stem cell-derived brain organoids replicate important stages of the prenatal human brain development and combined with the induced pluripotent stem cell (iPSC) technology offer an unprecedented model for investigating human neurological diseases including autism and microcephaly. We describe the history and birth of organoids and their application, focusing on cerebral organoids derived from embryonic stem cells and iPSCs. We discuss new insights into organoid-based model of schizophrenia and shed light on challenges and future applications of organoid-based disease model system. This review also suggests hitherto unrevealed potential applications of organoids in combining with new technologies such as nanophotonics/optogenomics for controlling brain development and atomic force microscopy for studying mechanical forces that shape the developing brain.


In vitro and in vivo reactions of nucleic acids with reducing sugars.
Reducing sugars such as glucose and glucose 6-phosphate have been shown to nonenzymatically react with the amino groups of proteins. The modification of proteins by reducing sugars can alter both physical characteristics and biological functions. Analogous to the reaction observed with proteins, the amino groups of DNA bases are also able to react nonenzymatically with reducing sugars. The modifications of DNA by reducing sugars result in the time- and sugar-concentration-dependent changes in biological properties. In this communication we review data describing in vitro and in vivo models we have used to investigate the biological consequences of the nonenzymatic glycosylation of DNA.


Spectroscopic molecular-fingerprint profiling of saliva.
Saliva analysis has been gaining interest as a potential non-invasive source of disease indicative biomarkers due to being a complex biofluid correlating with blood-based constituents on a molecular level. For saliva to cement its usage for analytical applications, it is paramount to gain underpinning molecular knowledge and establish a 'baseline' of the salivary composition in healthy individuals as well as characterize how these factors are impacting its performance as potential analytical biofluid. Here, we have systematically studied the molecular spectral fingerprint of saliva, including the changes associated with gender, age, and time. Via hybrid artificial neural network algorithms and Raman spectroscopy, we have developed a non-destructive molecular profiling approach enabling the assessment of salivary spectral changes yielding the determination of gender and age of the biofluid source. Our classification algorithm successfully identified the gender and age from saliva with high classification accuracy. Discernible spectral molecular 'barcodes' were subsequently constructed for each class and found to primarily stem from amino acid, protein, and lipid changes in saliva. This unique combination of Raman spectroscopy and advanced machine learning techniques lays the platform for a variety of applications in forensics and biosensing.


Impact of polyvascular disease on clinical outcomes in patients undergoing coronary revascularization: an observation from the CREDO-Kyoto Registry Cohort-2.
Patients with coronary artery disease (CAD) often have prior stroke or concomitant extra-cardiac vascular disease (EVD) such as cerebral, aortic, or peripheral vascular disease. However, clinical outcomes after coronary revascularization in patients with polyvascular disease have not been fully elucidated. Among 15,263 patients undergoing first coronary revascularization enrolled in the CREDO-Kyoto registry Cohort-2 from January 2005 to December 2007, there were 1443 patients with prior stroke (stroke + CAD group), 974 patients with EVD (EVD + CAD group), 253 patients with both prior stroke and EVD (stroke/EVD/CAD group) and 12,593 patients with neither prior stroke nor EVD (CAD alone group [reference]). The cumulative incidence of major adverse cardiovascular events (MACE: composite of cardiovascular death, myocardial infarction and stroke) through 3 years was significantly higher in patients with polyvascular disease compared with reference patients (19.9% in the stroke + CAD group, 18.5% in the EVD + CAD group, 20.1% in the stroke/EVD/CAD group, and 11.2% in the CAD alone group, P < 0.0001). After adjusting confounders, the presence of EVD and/or stroke was independently associated with higher risk for MACE compared with the reference group (adjusted HR [95%CI]: 1.34 [1.17-1.54], P < 0.0001 in the stroke + CAD group, 1.56 [1.32-1.84], P < 0.0001 in the EVD + CAD group, and 1.66 [1.24-2.23], P = 0.0007 in the stroke/EVD/CAD group). However, the presence of EVD and/or stroke was not associated with higher risk for myocardial infarction. Clinical outcome after coronary revascularization was worse in patients with prior stroke and/or EVD, which was mainly driven by the increased risk for non-coronary cardiovascular events.


Case-control study of completed ischemic stroke in the Parsis of Bombay: a population-based study.
All eligible adult cases of completed ischemic stroke (N = 112) derived from a prevalence survey of the Parsi community in Bombay, India, served as the basis of a case-control study of risk factors. The stroke morbidity rate in this group was similar to that reported for North America. A control subject free of stroke was selected randomly from the same population and matched to each case by age and sex. Information was obtained on various risk factors. Hypertension, both by history (odds ratio = 10.8) and by examination (odds ratio = 2.1), had a statistically significant association with stroke (p less than 0.01). This is one of the first community-based case-control studies of stroke in a large developing country.


A High Performing Zn-Ion Battery Cathode Enabled by In Situ Transformation of V2 O5 Atomic Layers.
Developing high capacity and stable cathodes is a key to successful commercialization of aqueous Zn-ion batteries (ZIBs). Pure layered V2 O5 has a high theoretical capacity (585 mAh g-1 ), but it suffers severe capacity decay. Pre-inserting cations into V2 O5 can substantially stabilize the performance, but at an expense of lowered capacity. Here we show that an atomic layer deposition derived V2 O5 can be an excellent ZIB cathode with high capacity and exceptional cycle stability at once. We report a rapid in situ on-site transformation of V2 O5 atomic layers into Zn3 V2 O7 (OH)2 ⋅2 H2 O (ZVO) nanoflake clusters, also a known Zn-ion and proton intercalatable material. High concentration of reactive sites, strong bonding to the conductive substrate, nanosized thickness and binder-free composition facilitate ionic transport and promote the best utilization of the active material. We also provide new insights into the V2 O5 -dissolution mechanisms for different Zn-salt aqueous electrolytes and their implications to the cycle stability.


Traversing psychological distance.
Traversing psychological distance involves going beyond direct experience, and includes planning, perspective taking, and contemplating counterfactuals. Consistent with this view, temporal, spatial, and social distances as well as hypotheticality are associated, affect each other, and are inferred from one another. Moreover, traversing all distances involves the use of abstraction, which we define as forming a belief about the substitutability for a specific purpose of subjectively distinct objects. Indeed, across many instances of both abstraction and psychological distancing, more abstract constructs are used for more distal objects. Here, we describe the implications of this relation for prediction, choice, communication, negotiation, and self-control. We ask whether traversing distance is a general mental ability and whether distance should replace expectancy in expected-utility theories.


Efficient Naphthalene Imide-Based Interface Engineering Materials for Enhancing Perovskite Photovoltaic Performance and Stability.
The ways to overcome surface charge recombination and poor interface contact are still the central challenges for the development of inorganic-organic hybrid halide perovskite solar cells (PSCs). [6,6]-Phenyl C61 butyric acid methyl ester (PCBM) is commonly employed in PSCs, but it has some disadvantages including high charge recombination and poor surface coverage. Therefore, the addition of an interfacial engineering layer showing efficient surface passivation, electron extraction, and excellent interface contact can solve the above problems. Furthermore, by employing interface engineering with a spike structure of the energy levels, the reduced energy losses are beneficial to elevating the open-circuit voltage (Voc) in PSCs. Herein, the linear naphthalene imide dimer containing an indacenodithiophene unit (IDTT2NPI) has been developed as an excellent interface engineering material to strengthen the perovskite performance. The introduction of a spike interface on the top of a methylammonium lead triiodide (MAPbI3) film resulted in a high Voc of 1.12 V with the optimal efficiency reaching 20.2%. The efficiency enhancement can be traced to the efficient surface passivation and enhanced interface contact. The mechanism of IDTT2NPI as the interface engineering layer was investigated by both experiments and theoretical calculations. This work provides a promising naphthalene imide-based interfacial material for high-efficiency and stable PSCs.


Parkinson's disease GWAS-linked Park16 carriers show greater motor progression.
Data on the long-term motor outcomes of genome-wide association study (GWAS)-linked Parkinson disease (PD) carriers are useful for clinical management. To characterise the association between GWAS-linked PARK16 gene variant and disease progression in PD over a 9-year time frame. Over a 9-year period, carriers of PARK16 rs11240572 variant and non-carriers were followed up and evaluated using the modified Hoehn and Yahr (H&Y) staging scale and Unified Parkinson's Disease Rating Scale (UPDRS) part III. A longitudinal, linear mixed model was performed to compare the changes of H&Y staging scale, UPDRS motor score and UPDRS subscores between the two groups. A total of 156 patients (41 PARK16 carriers and 115 non-carriers) were evaluated and followed up for up to 9 years. Using longitudinal linear mixed model analysis, there was a greater rate of deterioration in the motor function as measured by the UPDRS scores compared with non-carriers after 5 years from the date of diagnosis (p=0.009). In addition, we demonstrated that PARK16 variant carriers had worse gait scores (p=0.043) and greater motor progression than non-carriers after 6 years based on the modified H&Y staging scale (p=0.040). In a 9-year longitudinal study, we demonstrated that PD PARK16 variant carriers exhibited greater motor progression after 5 years of disease compared with non-carriers, suggesting that GWAS-linked gene variants may influence disease progression over time. Closer monitoring and management of these higher risk patients can facilitate a better quality of life.


Widely tunable compact terahertz gas lasers.
The terahertz region of the electromagnetic spectrum has been the least utilized owing to inadequacies of available sources. We introduce a compact, widely frequency-tunable, extremely bright source of terahertz radiation: a gas-phase molecular laser based on rotational population inversions optically pumped by a quantum cascade laser. By identifying the essential parameters that determine the suitability of a molecule for a terahertz laser, almost any rotational transition of almost any molecular gas can be made to lase. Nitrous oxide is used to illustrate the broad tunability over 37 lines spanning 0.251 to 0.955 terahertz, each with kilohertz linewidths. Our analysis shows that laser lines spanning more than 1 terahertz with powers greater than 1 milliwatt are possible from many molecular gases pumped by quantum cascade lasers.


Nutrient consumption of individuals taking or not taking nutrient supplements.
Mean energy and nutrient intakes from food of 150 users or non-users of nutrient supplements were compared. Independent of supplement use, no significant differences in nutrient intakes between the two groups were observed. Some significant differences were noted in average nutrient intakes between men and women of the same age group. Fifty-three percent of the subjects reported the use of supplements, with multivitamins and ascorbic acid most often taken. Potentially toxic intakes of vitamins A, C, and E were observed for a few subjects. In general, nutrient intakes from food met the Recommended Dietary Allowances.


Determination of pulmonary capillary wedge pressure using pulsed wave Doppler echocardiography: clinical application of range ambiguity phenomenon.
To predict pulmonary capillary wedge pressure (PCWP) noninvasively, several Doppler combination indices have been developed. Recently, a fair correlation has been found between the time constant of isovolumic left ventricular (LV) relaxation (tau) and pulsed wave Doppler LV inflow propagation velocity (LVIPVpw) derived through the application of range ambiguity phenomenon. In the measurement of LVIPVpw, we can simultaneously measure the peak phantom E-wave velocity (Ep) from the same heartbeat. Hence, it is hypothesized that Ep/LVIPVpw is a useful index in predicting PCWP. In all, 29 patients who underwent elective cardiac catheterization for suggested coronary artery disease were included. Mean PCWP (mPCWP) obtained from right heart catheterization was compared with echocardiographic data before and 5 minutes after sublingual application of nitroglycerin (0.6 mg). Nitroglycerin caused a significant decrease in Ep and mPCWP, but not in LVIPVpw (P < .001, P < .001, and P = .687, respectively). By stepwise multiple linear regression analysis, only the Ep/LVIPVpw (beta = 0.832, P < .001) was the independent predictor of mPCWP. After nitroglycerin intake, the change in mPCWP was significantly correlated with the change in Ep/LVIPVpw (r = 0.455, P = .015). The sensitivity and specificity of Ep/LVIPVpw > 0.74 in predicting mPCWP > 15 mm Hg were 78% and 90%, respectively (area under curve 0.86). In conclusion, Ep/LVIPVpw derived from the same heartbeat provides a good estimate of mPCWP and can be used to rapidly track the change in mPCWP.