Modulation of microglial metabolism facilitates regeneration in demyelination.
Microglia exhibit diverse phenotypes in various central nervous system disorders and metabolic pathways exert crucial effects on microglial activation and effector functions. Here, we discovered two novel distinct microglial clusters, functionally associated with enhanced phagocytosis (PEMs) and myelination (MAMs) respectively, in human patients with multiple sclerosis by integrating public snRNA-seq data. Microglia adopt a PEMs phenotype during the early phase of demyelinated lesions, predominated in pro-inflammatory responses and aggravated glycolysis, while MAMs mainly emerged during the later phase, with regenerative signatures and enhanced oxidative phosphorylation. In addition, microglial triggering receptor expressed on myeloid cells 2 (Trem2) was greatly involved in the phenotype transition in demyelination, but not indispensable for microglia transition toward PEMs. Rosiglitazone could promote microglial phenotype conversion from PEMs to MAMs, thus favoring myelin repair. Taken together, these findings provide insights into therapeutic interventions targeting immunometabolism to switch microglial phenotypes and facilitate regenerative capacity in demyelination.


Is it possible to optimise the labour and time intensity of diatom analyses for determination of the Polish Diatom Indices (IO, IOJ)?
Diatom-based indices are a recommended approach in the assessment of the ecological status of lakes and rivers, required by the EU Water Framework Directive. To optimise the time-consuming microscopic analyses, we determined the lowest number of diatom valves needed to be identified ('counted') in a sample to arrive at a reliable ecological status assessment based on the Polish multimetric diatom indices (diatom index, IO for rivers, and diatom index for lakes, IOJ). We compared the indices calculated with different valve counts. The dataset consisted of diatom counts in 55 samples collected in the rivers Ina and Drawa (Western Pomerania, NW, Poland) and their lakes. Following the method used by the Polish Chief Inspectorate for Environmental Protection (ChIEP), periphyton samples were collected from macrophytes growing in the rivers and lakes, and diatom slides were prepared. Originally, the ecological status was determined based on identifying 400 valves per slide. In the subsequent simulation, 50, 100, 150, 200, 250, 300, 350 and 400 valves per slide were randomly drawn 20 times for each sample and each simulation, and the indices were calculated again. In 87% of our simulations, the ecological status turned out to be identical, regardless of the number of valves identified. However, the standard deviation of the index values was at its highest (> 0.05) with 50 valves, and decreased systematically (below 0.05) for 100 and more valves. Simulated datasets showed logarithmic trend of changes where the compilation and standard deviation was stable above 200 valves identified. Therefore, we recommend simplified methodology for Polish multimetric diatom indices. Reduction of identified valve quantity in a sample to 200 valves would result in over 95% of compliance with classification obtained when 400 valves were identified.


Evaluation of urinary and faecal continent stomas.
To evaluate the outcome and complications of urinary and faecal continent catheterizable stomas. Retrospective record review of all patients operated on in our institution within the last 6 years. Fifty-five children received 63 stomas. The mean age at operation was 9.2 years and the mean follow-up period was 2.8 years. The diagnoses were: neurogenic bladder (n=22), bladder or cloacal exstrophy (n=20), anorectal malformation (n=6), persistent cloaca (n=3), Hirschsprung's disease (n=2), posterior urethral valves (n=1) and prune belly syndrome (n=1). There were 35 urinary stomas and 28 faecal stomas. Eight patients received both stomas. Both the appendix and a transverse tubularized intestinal segment (Yang-Monti technique) were used; in some cases a caecal flap was created. In three patients the appendix was divided and used to construct two stomas. The implantation of urinary stomas was into the native bladder in 24 patients and into the intestinal segment of an augmented bladder in 11 cases. The location of the stoma was umbilical in 20 cases, right lower quadrant of the abdomen in 35, neo-umbilicus in five and left lower quadrant in three. When an extra-umbilical location was chosen skin flaps were used. Excellent cosmetic and functional results were achieved in 53 (84.2%) of the 63 stomas, which are continent and easy to catheterize. Two had acceptable results with minor problems. There were eight re-operations (12.6% of stomas, 14.5% of patients). The reasons for the re-operations were difficult catheterization in two, incontinence in three, and mucosal prolapse in three patients in whom skin flaps were not used. Of the eight re-operations, seven were in urinary stomas and one in a faecal stoma. Urinary incontinence was attributed to shortening of the intravesical tunnel. No difference in results was observed between the different techniques used, with the exception that cutaneous anastomosis without skin flaps had to be revised because of prolapse, and two out of three incontinent channels had been constructed with tubularized ileum. Catheterizable continent urinary and faecal stomas achieve the objectives of urinary and faecal continence and independence in most patients with a low complication rate.


Phenolic compounds with pancreatic lipase inhibitory activity from Korean yam (Dioscorea opposita).
Abstract Twenty-three phenolic compounds were isolated from Dioscorea opposita by bioactivity-guided method and their inhibitory effect against pancreatic lipase was evaluated. A total of 15 isolates reduced lipase activity at IC50 values of less than 50 µM and 3,3',5-trihydroxy-2'-methoxybibenzyl showed the highest inhibition with an IC50 value of 8.8 µM. This study is a first to reveal the pancreatic lipase inhibitory activity by both D. opposita and its isolated compounds.


Epidemiological survey on Escherichia coli O157 in Chongqing and Three-Gorge Reservoir Areas of China.
Prevalence, presence of virulence and adherence associated genes, genetic diversity, biochemical characteristics, and antibiotic susceptibility were determined for Escherichia coli O157 isolated over 4 months in Chongqing city and Three-Gorge Reservoir Areas. 11 isolates of E. coli O157 were isolated from 1504 samples and 7 of them are O157:H7 and 4 are O157:H? All O157:H7 isolates had eaeA, ehxA, EspA and Tccp genes, but did not have stx1 and stx2. All O157:H? isolates did not have stx1, stx2, eaeA, ehxA, EspA and Tccp genes except for the isolate obtained from Yunyang county which had stx1. When eaeA and ehxA presented in isolates were digested by restriction enzymes, the numbers and the sizes of the segments were the same as the control E. coli O157 strains. This suggests that eaeA and ehxA exhibit poor polymorphism. Most E. coli O157 isolates showed identical biochemical activities to the standard strains for sorbitol and rhamnose, and all E. coli O157:H7 obtained from feces at the same dairy cattle farm had similar biochemical characteristics. Antibiotic susceptibility demonstrated resistance of the isolates to penicillin, ampicillin, bacitracin, cefuroxime, erythromycin, gentamycin and tetracycline, indicating the isolates obtained in this study had a multi-drug resistance.


Dual-wavelength UV-visible metalens for multispectral photoacoustic microscopy: A simulation study.
Photoacoustic microscopy is advancing with research on utilizing ultraviolet and visible light. Dual-wavelength approaches are sought for observing DNA/RNA- and vascular-related disorders. However, the availability of high numerical aperture lenses covering both ultraviolet and visible wavelengths is severely limited due to challenges such as chromatic aberration in the optics. Herein, we present a groundbreaking proposal as a pioneering simulation study for incorporating multilayer metalenses into ultraviolet-visible photoacoustic microscopy. The proposed metalens has a thickness of 1.4 µm and high numerical aperture of 0.8. By arranging cylindrical hafnium oxide nanopillars, we design an achromatic transmissive lens for 266 and 532 nm wavelengths. The metalens achieves a diffraction-limited focal spot, surpassing commercially available objective lenses. Through three-dimensional photoacoustic simulation, we demonstrate high-resolution imaging with superior endogenous contrast of targets with ultraviolet and visible optical absorption bands. This metalens will open new possibilities for downsized multispectral photoacoustic microscopy in clinical and preclinical applications.


Ovarian survival after pelvic radiation: transposition until the age of 35 years.
To evaluate the effectiveness of ovarian transposition (OT) prior to radiation therapy (RT) and to evaluate the effect of age on ovarian survival (OS) after OT. We performed a retrospective control study, with women (aged < 45 years) who underwent OT prior to pelvic radiation, versus women diagnosed with cervical cancer and treated with hysterectomy/trachelectomy and radiation therapy. All women were treated between 1989 and 2010. The 5 years OS rate was calculated, with a sub-analysis for age (25-30; 31-35 and 36-40 years). Ovarian failure was defined as climacteric complaints (with or without starting hormone replacement therapy) and/or laboratory measurements (FSH > 40 IU/L and/or estradiol < 100 pmol/L), or bilateral salpingo oophorectomy. Women were censored at recurrence. Twenty-seven women after OT and 29 controls were included. The radiation dose was 44.8 Gy (25.0-63.0 Gy) and 46.3 Gy (45.0-50.0 Gy), respectively. The 5-year ovarian survival rate was 60.3% versus controls 0% (p < 0.001 95% CI 3.48-11.50). Despite the decrease in ovarian survival after OT with increasing age, in all age groups (25-30, 30-35 and 35-40) ovarian survival after OT was significantly better compared to women without OT (p = 0.001; p = 0.004 and p = 0.000, respectively). Neither intra-vaginal radiation therapy of concomitant chemotherapy in addition to pelvic radiation significantly altered ovarian survival. Our data shows that ovarian transposition prior to pelvic radiation is effective in women until the age of 35 years and needs to be discussed in patients aged 36-40 years.


Individual and contextual level enablers and barriers determining electronic community health information system implementation in northwest Ethiopia.
The government of Ethiopia has envisioned digitalizing primary healthcare units through the electronic community health information system (eCHIS) program as a re-engineering strategy aiming to improve healthcare data quality, use, and service provision. The eCHIS is intended as a community-wide initiative to integrate lower health structure with higher administrative health and service delivery unit with the ultimate goal of improving community health. However, the success or failure of the program depends on the level of identifying enablers and barriers of the implementation. Therefore, this study aimed to explore individual and contextual-level enablers and barriers determining eCHIS implementation. We conducted an exploratory study to determine the enablers and barriers to successfully implementing eCHIS in rural Wogera district, northwest Ethiopia. In-depth interviews and key informant interviews were applied at participants from multiple sites. A thematic content analysis was conducted based on the key themes reported. We applied the five components of consolidated framework for implementation research to interpret the findings. First, based on the intervention's characteristics, implementers valued the eCHIS program. However, its implementation was impacted by the heavy workload, limited or absent network and electricity. Outer-setting challenges were staff turnover, presence of competing projects, and lack of incentive mechanisms. In terms of the inner setting, lack of institutionalization and ownership were mentioned as barriers to the implementation. Resource allocation, community mobilization, leaders' engagement, and availability of help desk need emphasis for a better achievement. With regard to characteristics of the individuals, limited digital literacy, older age, lack of peer-to-peer support, and limited self-expectancy posed challenges to the implementation. Finally, the importance of mentoring and engaging community and religious leaders, volunteers, having defined plan and regular meetings were identified elements of the implementation process and need emphasis. The findings underlined the potential enablers and barriers of eCHIS program for quality health data generation, use, and service provision and highlighted areas that require emphasis for further scale-up. The success and sustainability of the eCHIS require ongoing government commitment, sufficient resource allocation, institutionalization, capacity building, communication, planning, monitoring, and evaluation.


Design of spread-out Bragg peaks in hadron therapy with oxygen ions.
Design of a numerical method for creating spread-out Bragg peak (SOBP) and evaluation of the best parameter in Bortfeld Model to this aim in oxygen ion therapy. In radiotherapy, oxygen ions have more biological benefits than light beams. Oxygen ions have a higher linear energy transfer (LET) and larger relative biological effectiveness (RBE) than lighter ones. For the design of the spread-out Bragg peak (SOBP) for oxygen beam, we designed a numerical method using the Geant4 Monte Carlo simulation code, along with matrix computations. The profiles of the Bragg Peak have been calculated for each section in the target area by the Geant4 tool. Then, in order to produce SOBP smoothly, a set of weighting factors for the intensity of oxygen ion radiation in each energy was extracted through a numerically designed method. This method was tested for producing SOBP at various widths and at different depths of a phantom. Also, weighting factors of intensity for producing a flat SOBP with oxygen ions were also obtained using the Bortfeld model in order to determine the best parameters. Then, the results of the Bortfeld model were compared with the outcomes of the method that was developed in this study. The results showed that while the SOBP designed by the Bortfeld model has a homogeneity of 92-97%, the SOBP designed by the numerical method in the present study is above 99%, which in some cases even closed to 100%.


One-stop-shop preoperative evaluation for living liver donors with gadoxetic acid disodium-enhanced magnetic resonance imaging: efficiency and additional benefit.
To explore the efficiency, cost, and time for examination of one-stop-shop gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in preoperative evaluation for parent donors by comparing with multidetector computer tomography combined with conventional MR cholangiopancreatography (MDCT-MRCP). Forty parent donors were evaluated with MDCT-MRCP, and the other 40 sex-, age-, and weight-matched donors with Gd-EOB-DTPA-enhanced MRI. Anatomical variations and graft volume determined by pre- and intra-operative findings, costs and time for imaging were recorded. Image quality was ranked on a 4-point scale and compared between both groups. Gd-EOB-DTPA-enhanced MRI provided better image quality than MDCT-MRCP for the depiction of portal veins and bile ducts by both reviewers (p < 0.05), hepatic veins by one reviewer (p < 0.05), rather hepatic arteries by both reviewers (p < 0.01). Sixty-nine living donors proceeded to liver donation with all anatomical findings accurately confirmed by intra-operative findings. The "in-room" time of Gd-EOB-DTPA-enhanced MRI was 12 min longer than MDCT-MRCP. Gd-EOB-DTPA-enhanced MRI was cheaper than MDCT-MRCP (US$519.72 vs. US$631.85). One-stop-shop Gd-EOB-DTPA-enhanced MRI has similar diagnostic accuracy as MDCT-MRCP and can provide additional benefit in terms of costs and convenience in preoperative evaluation for parent donors.


Synthesis of T-705-Ribonucleoside and T-705-Ribonucleotide and Studies of Chemical Stability.
T-705 (favipiravir) is a fluorinated hydroxypyrazine carboxamide that exhibits antiviral activities against a variety of RNA viruses. Given the lack of potent agents to combat these infections caused by a large number of high-impact pathogens, significant emphasis has been put on studies of the antiviral properties of T-705 and its mechanism of action. T-705 acts as a nucleobase analogue; it is therefore metabolized to the corresponding ribonucleoside triphosphate intracellularly. Herein we report a reliable synthesis of T-705-ribonucleoside as well as its 5'-monophosphate. Moreover, we disclose detailed studies on the remarkable lability of the heterocycle when attached to ribose under very mild conditions, as typically applied in biochemical studies.


Effects of prolactin on intracellular calcium concentration and cell proliferation in human glioma cells.
Prolactin (PRL) has several physiological effects on peripheral tissues and the brain. This hormone acts via its membrane receptor (PRL-R) to induce cell differentiation or proliferation. Using reverse transcription-polymerase chain reaction (RT-PCR) combined with Southern blot analysis, we detected PRL-R transcripts in a human glioma cell line (U87-MG) and in primary cultured human glioblastoma cells. These transcripts were deleted or not in their extracellular domains. We examined the effects of PRL on intracellular free Ca2+ concentration ([Ca2+](i)) in these cells in order to improve our understanding of the PRL transduction mechanism, which is still poorly documented. [Ca2+](i) was measured by microspectrofluorimetry using indo-1 as the Ca2+ fluorescent probe. Spatiotemporal aspects of PRL-induced Ca2+ signals were investigated using high-speed fluo-3 confocal imaging. We found that physiological concentrations (0.4-4 nM) of PRL-stimulated Ca2+ entry and intracellular Ca2+ mobilization via a tyrosine kinase-dependent mechanism. The two types of Ca2+ responses observed were distinguishable by their kinetics: one showing a slow (type I) and the other a fast (type II) increase in [Ca2+](i). The amplitude of PRL-induced Ca2+ increases may be sufficient to provoke several physiological responses, such as stimulating proliferation. Furthermore, PRL induced a dose-dependent increase in [3H]thymidine incorporation levels and in cellular growth and survival, detected by the MTT method. These data indicate that PRL induced mitogenesis of human glioma cells.


The extracellular matrix during neural crest formation and migration in rat embryos.
Changes in the distribution of extracellular matrix components have been investigated immunohistochemically during neural crest development in the rat. Inside the ectodermal epithelium basal lamina components are formed resulting in a separation of neurectoderm and epidermal ectoderm. Within the presumptive neural crest area fibronectin, hyaluronan and chondroitin sulphate become apparent. Upon subsequent neural crest migration the basal lamina becomes disrupted. As the neural crest cells take part in mesectoderm formation, fragments of the basal lamina remain attached to their surface, as is demonstrated with antibodies against laminin and collagen type IV. The extracellular matrix is therefore active both in the separation of neuroectoderm from epidermal ectoderm and in mesectoderm formation.


Chemical synthesis of amphiphilic glycoconjugates: Access to amino, fluorinated and sulfhydryl oleyl glucosides.
Amphiphilic glycoconjugates offer an important prospect for development as chemical biology tools and biosurfactants. The chemical synthesis of such materials is required to expedite such prospect, compounded by the example of oleyl glycosides. Herein, we report a mild and reliable glycosylation method to access oleyl glucosides, glycosidating oleyl alcohol with α-trichloroacetimidate donors. We demonstrate capability for this methodology, extending it to synthesise the first examples of pyranose-component fluorination and sulfhydryl modifications within glucosides and glucosamines of oleyl alcohol. These compounds provide an exciting series of tools to explore processes and materials that utilise oleyl glycosides, including as probes for glycosphingolipid metabolism.


Differential expression of genes involved in cGMP-dependent nitric oxide signaling in murine embryonic stem (ES) cells and ES cell-derived cardiomyocytes.
Nitric oxide (NO) performs multiple physiological roles as a biological signaling molecule. The role of NO and cGMP signaling in embryonic stem (ES) cell-derived cardiomyocytes (CM) has been investigated but many questions remain. In this study, we examined the expression of the NO signaling pathway components nitric oxide synthase (NOS-1, 2, 3), soluble guanylyl cyclase (sGCalpha(1) and beta(1)) and protein kinase G (PKG) genes and sGC activity in murine ES cells subjected to differentiation by embryoid body (EB) formation. We found that in undifferentiated ES cells, NOS-1, NOS-3, and sGCbeta(1) were detected while NOS-2, sGCalpha(1), and PKG were very low or undetectable. When ES cells were subjected to differentiation, NOS-1 abruptly decreased within one day, NOS-2 mRNA became detectable after several days, and NOS-3 increased after 7-10 days. Levels of sGCalpha(1), sGCbeta(1), and PKG all increased gradually over a several day time course of differentiation in EB outgrowths. Analysis of sGC activity in cell lysates derived from undifferentiated ES cells revealed that NO could not stimulate cGMP. However, lysates from differentiated EB outgrowths produced abundant cGMP levels after NO stimulation. Purification of ES-cell derived CM revealed that mRNA expression of all the NOS isoforms was very low to absent while sGCalpha(1) and beta(1) subunit mRNAs were abundant and sGC-mediated cGMP production was apparent in this population of cells. These data suggest that cGMP-mediated NO signaling may play a minor role, if any, in undifferentiated ES cells but could be involved in the early differentiation events or physiological processes of ES cells or ES cell-derived lineages.


Fluoride Varnish in Nursery Schools: A Randomised Controlled Trial - Protecting Teeth @3.
Studies suggest that fluoride varnish (FV) application can reduce dental caries in child populations. The multiple-component national child oral health improvement programme in Scotland (Childsmile) includes nursery-based universal supervised toothbrushing and deprivation-targeted FV applications, together with community and dental practice prevention interventions. This trial, a double-blind, two-arm randomised control trial, aimed to assess the effectiveness and cost-effectiveness of the nursery-based FV applications plus treatment-as-usual (TAU) Childsmile programme interventions, compared to TAU Childsmile interventions alone, in children not targeted to receive nursery FV as part of the programme. Participating children in the first year of nursery (aged three), with or without existing caries, were randomised to either FV or TAU and followed up for 24 months until the first year of primary school. Treatments were administered at six-monthly intervals. The primary endpoint was "worsening of d3mft" from baseline to 24 months. Secondary endpoints were worsening of d3mfs, d3t, mt, and ft. Individual record-linkage captured wider programme activities and tertiary endpoints. A total of 1,284 children were randomised, leading to 1,150 evaluable children (n = 577 FV, n = 573 TAU, 10% dropouts). Mean age was 3.5 years, 50% were female (n = 576), 17% had caries at baseline (n = 195), all balanced between the groups. Most children received three/four treatments. Overall, 26.9% (n = 155) had worsened d3mft in the FV group, and 31.6% (n = 181) in the TAU group, with an odds ratio (OR) of 0.80 (0.62-1.03), p = 0.078. The results for worsening of the secondary endpoints were: d3mfs 0.79 (0.61-1.01) p = 0.063, d3t 0.75 (0.57-0.99) p = 0.043, mt 1.34 (0.75-2.39) p = 0.319, and ft 0.77 (0.53-1.14) p = 0.191. We calculated a number needed to treat of 21 and a cost of GBP 686 to prevent a single worsening of d3mft. There was a modest non-significant reduction in the worsening of d3mft in the nursery FV group compared to TAU, suggesting that this intervention is unlikely to represent an effective or cost-effective addition to the population oral health improvement programme.


Preferential use of vein for above-knee femoropopliteal grafts.
Many centres preferentially use polytetrafluoroethylene (PTFE) for above-knee femoropopliteal bypass as surgery is simplified and patency rates are comparable to vein, which is preserved for subsequent revisions or for distal disease progression. In this Unit, vein remains first choice graft material. The aim of this study was to audit our results with respect to above-knee bypass to establish the demand for vein for secondary reconstruction and to document the ultimate fate of the limb. Between 1983 and 1992, 112 above-knee reconstructions were performed on 109 patients (89 vein and 23 PTFE grafts). PTFE was used where vein was absent or inadequate. Life table analysis of primary graft patency, limb salvage and patient survival up to 36 months follow-up concurs with previously reported series. Twenty-eight vein grafts (31%) and 11 PTFE grafts (48%) occluded during a median follow-up of 64 months (8-116 months). In only four cases was vein required for secondary procedures. The remainder were salvaged by thrombectomy and local procedures for technical problems. Amputation rates following graft occlusion were 12% in the vein group (20% of these being above-knee) as against 26% in the PTFE group (80% above knee). The demand for vein for secondary procedures is low. Amputation rates when vein grafts do occlude are half those of PTFE and amputation level is significantly influenced by graft type. We advocate preferential use of vein in above-knee femoropopliteal bypass.


Assessment of practices for suspended oral drugs by tablet crushing in pediatric units.
The aim of this study was to assess the impact of suspended drug by tablet crushing in our pediatric hospital in term of targeted dose and to identify parameters involved in the potential variability. Four usually crushed pediatric drug substances were selected: amiodarone, warfarin, hydrocortisone and captopril. Each tablet was crushed in a bag using a crusher device. Once crushed, a pre-determined volume of water was added using oral syringes before taking the necessary volume to obtain the targeted drug amount. For each drug, operators among pharmacy technicians and nurses investigated 2 targeted doses (high and low). Each suspension was assayed 3 times using the corresponding validated HPLC procedure. Statistical analysis was performed (GraphPad Prism®) to evaluate the impact of operators, the level of suction in bag, and actual drug doses. To investigate the impact of formulation change on syringe drug content, five generic drugs of amiodarone were selected. Syringes contents were compared using one-way ANOVA. Drug loss in syringe ranged from 8.1% to 54.1%. The drug loss represented 18.9% to 30.5% for amiodarone, 0.1% to 5.5% for captopril, 5.6% to 19.7% for warfarin and 5.0% to 30.7% for hydrocortisone. The comparison of level sampling of suspensions presented significant differences for amiodarone, hydrocortisone, and warfarin. Comparison of operators demonstrated significant difference between pharmacy technician and nurse (p = 0.0251). Finally, comparison of 5 generic drugs for amiodarone showed some statistical difference between the syringes content obtained when using the original medicine as compared to the generics. The physicochemical properties of each drug substance and the formulation of the drug product may both factor that should be considered. As a result, crushing tablets in water for oral administration needs a case by case assessment. Although appropriate pediatric formulations are lacking, suspend the crushed material in a given volume of water should be discouraged and not recommended because far from good practice.


How does brain MRI lesion volume change on serial scans in patients with multiple sclerosis?
Although lesion load changes on conventional T2-weighted brain magnetic resonance imaging (MRI) scans from patients with multiple sclerosis (MS) are used to monitor the effect of treatment, there is no clear definition of how lesion load changes over years according to the lesion load present at a baseline evaluation. In the present study, we evaluated the relationship between lesion load changes over time and lesion load at a baseline evaluation in a group of untreated patients with MS. We scanned nineteen patients on two separate occasions with a mean interval 16.4 months between the two examinations. In each scanning session, a scan with forty contiguous 3-mm-thick axial slices was acquired. We assessed MRI lesion loads using a semi-automated local thresholding technique. Both a linear (p < 0.0001) and a quadratic component (p = 0.0008) of the baseline volume were significant in describing the follow-up volume. The equation to model this finding was as follows: Vf = beta0 Vb + beta1 (Vb)2, where Vf is the lesion volume at follow-up, Vb is the lesion volume at baseline, beta0 = 0.834 (SE = 0.098), and beta1 = 0.014 (SE = 0.003) (mL)(-1). Our data indicate that lesion volume changes detectable on serial brain MRI studies from patients with MS are dependent on the extent of lesion burden present on the baseline MRI scans. This finding has to be considered when planning phase III trials.


High-density lipoprotein cholesterol efflux capacity in patients with obstructive sleep apnea and its relation with disease severity.
Obstructive sleep apnea (OSA) is linked to an accelerated risk of cardiovascular disease (CVD). Some key CVD risk factors are present in patients suffering from OSA such as hypertension, inflammation, oxidative stress, and dyslipidemia. High-density lipoprotein (HDL) cholesterol efflux capacity (CEC) is proposed as a reliable biomarker of HDL function and the present study aimed to quantify this biomarker in patients with OSA. ATP binding cassette subfamily A member 1 (ABCA1), non-ABCA1, and total CEC were determined in 69 polysomnographic-confirmed OSA patients and 23 controls. Moreover, paraoxonase (PON) activities, high-sensitivity C-reactive protein (hsCRP), apolipoprotein B (apo B), and apolipoprotein A-I (apo A-I) circulating levels were quantified in the studied population. All CEC measures were reduced in the OSA group compared to the control group. Strikingly, ABCA1 CEC was diminished in severe OSA in comparison with mild OSA. Furthermore, PON activities and apo A-I showed lower levels, while hsCRP and apo B were elevated in OSA patients compared to controls. Moreover, ABCA1 CEC showed an inverse association with hsCRP and a positive association with apo A-I, while non-ABCA1 CEC presented an association with HDL-C. These results suggest the presence of an impaired HDL function in OSA. In particular, ABCA1 CEC was associated with disease severity and inflammation which could be a factor increasing the risk of CVD.


Different pathways mediate virus inducibility of the human IFN-alpha 1 and IFN-beta genes.
Multimerization of GAAANN generates sequences frequent in virus-inducible promoters. We distinguished different types of (GAAANN)4 sequences mediating virus inducibility. Type I (NN = GT, GC, CT, or CC) responds to IFNs and to IRF-1 and causes silencing. Type II (NN = TG) and type III (NN = CG) neither silence nor respond to IRF-1 or IFN. Type III mediates constitutive transcription and binds the constitutive IEFga factor, whereas type II binds the novel "TG protein". IFN-beta and IFN-alpha 1 promoters contain different response elements: The former has a type I-like sequence (PRDI) and an NF-kappa B-binding sequence (PRDII); the latter has a type II-like "TG sequence" and possibly additional elements but does not bind NF-kappa B. Type I, type II, and NF-kappa B elements represent three distinct terminal pathways mediating virus induction.


Changes in border movement of the mandible in skeletal Class III before and after orthognathic surgery.
The purpose of this study was to examine the changes in border movement of the mandible before and after mandibular ramus osteotomy in patients with prognathism. The subjects were 73 patients with mandibular prognathism who underwent sagittal split ramus osteotomy (SSRO) with and without Le Fort I osteotomy. Border movement of the mandible was recorded with a mandibular movement measure system (K7) preoperatively and at 6 months postoperatively. Of the 73 patients, 21 had measurements taken at 1.5 years postoperative. Data were compared between the pre- and postoperative states, and the differences analyzed statistically. There was no significant difference between SSRO alone and SSRO with Le Fort I osteotomy in the time-course change. The values at 6 months postoperative were significantly lower than the preoperative values for maximum vertical opening (P=0.0066), maximum antero-posterior movement from the centric occlusion (P=0.0425), and centric occlusion to maximum opening (P=0.0300). However, there were no significant differences between the preoperative and 1.5 years postoperative measurements. This study suggests that a postoperative temporary reduction in the border movement of the mandible could recover by 1.5 years postoperative, and the additional procedure of a Le Fort I osteotomy does not affect the recovery of mandibular motion after SSRO.


Distribution patterns of torpedo maculopathy: Further evidence of a congenital retinal nerve fiber layer-driven etiology.
With fewer than 100 peer-reviewed cases reported in the world to date, the underlying etiology of torpedo maculopathy has remained elusive. In this literature review, we provide new evidence to better support, reject and unify claims regarding cause, diagnosis, and proper clinical management of this disease. We reviewed 44 case reports and case series, which included 77 patients (after exclusions). We additionally introduced 3 new cases from our clinical practice for a total of 80 cases. Ages at presentation ranged from 6 months old to 73 years old (mean: 24.2 years old). The nasal aspects of torpedo maculopathy lesions pointed toward the optic disc and localized to a kite-shaped region of the temporal macula, correlating with the anatomic junction of the superior arcuate, inferior arcuate, and papillomacular bundles of retinal nerve fiber layer distribution. No patterns were observed among the temporal aspects of the lesions. These findings support a congenital etiology of torpedo maculopathy and a possible influence of the retinal nerve fiber layer in the development of mature retinal pigment epithelium.


Effect of the association time of in vivo bound prolactin on the [125I]prolactin receptor assays of female rat livers.
Significantly (P less than 0.01) reduced 125I-labeled ovine prolactin binding (mean, --22%), as a result of an ether anesthesia-reduced rise in serum prolactin, was observed in plasma membrane preparations of liver samples of female rats taken after 5 min of etherization when compared to samples taken from the same animals during the first minute of etherization. This reduction in assayable receptors occurred after 1 h but not 2 h of assay incubation time. Significantly (P less than 0.05) reduced 125I-labeled ovine prolactin binding (mean, --16%) was also observed in liver samples exposed to a 30-min ether-induced rise in serum prolactin when compared to liver samples taken during the first minute of etherization. In contrast, this reduction was apparent at assay incubation times of 1, 2 and 4 h but not at 10 h. These results suggest that serum prolactin can bind to prolactin receptors in vivo and partially block subsequent 125I-labeled ovine prolactin receptor assay. In addition, these data provide evidence that a complex time-dependent binding of prolactin may occur in the plasma of the female rat liver.


Lordosis behavior in males of two inbred strains of guinea pig.
The lordosis behavior of male guinea pigs from inbred strains 2 and 13 was examined. Significantly more isolated gonadally intact males of strain 2 than strain 13 displayed lordosis. Castration did not decrease the display of lordosis. In castrated strain 2 males, those which showed lordosis did not have higher plasma androgen, estrone or estradiol levels than those which did not show lordosis. They also did not differ hormonally from ovariectomized strain 2 females even though strain 2 females never showed lordosis without hormone replacement. Although the lordosis shown by strain 2 males was not related to endogenous gonadal hormone levels, estradiol benzoate (EB) administration facilitated lordosis. EB had no clear effect on lordosis in strain 13 males. Progesterone after EB priming had no further facilitative effect in males of either strain. These results indicate that lordosis is more readily elicited from strain 2 than strain 13 males. Furthermore, lordosis in strain 2 males is not dependent upon gonadal hormones for its display although it is facilitated by EB (but not progesterone).


Topical tacrolimus in the treatment of inverse psoriasis in children.
Inverse psoriasis is a chronic disease frequently treated with topical corticosteroids. This retrospective case study evaluated the efficacy of tacrolimus 0.1% ointment to treat inverse psoriasis in children. Twelve of 13 patients had complete clearance of their psoriatic lesions within 2 weeks after initiating treatment with topical tacrolimus 0.1%.


Genomic organization and functional analysis of the gene encoding the Krüppel-like transcription factor KLF6.
The Krüppel-like transcription Factor 6 (KLF6) is regulated during cell proliferation and differentiation events like mammalian development and tissue regeneration, while its aberrant expression is associated with tumor formation. To investigate KLF6 transcriptional control, the genomic organization of human KLF6 together with its cis-regulatory region was analyzed. A high sequence homology of KLF6 regulatory regions was found in mammals, which in turn predicts a high degree of evolutionary conserved transcriptional mechanisms. A transcription start site was identified at the first nucleotide downstream of a potential initiator element. Also, the role of KLF6 regulatory regions was determined by transfection experiments. A minimal promoter region lacking a TATA-box yet containing an Initiator was identified and found to be active in all cells analyzed. In addition, two strong activating sequences were located between positions -407/-344 and -307/-207, where the latter contained Sp1 and CAAT-box sites. Furthermore, ectopic expression of Sp1 increased the transcriptional activity of the KLF6 promoter. In conclusion, our data revealed that KLF6 gene transcription is under control of a TATA-box independent initiation mechanism together with an evolutionary conserved array of positive cis-acting elements.


The effect of bleaching on shear bond strength of brackets bonded with a resin-modified glass ionomer.
This study assessed the effect of a 35% hydrogen peroxide bleaching gel on the shear bond strength and bond failure site of a resin-modified glass ionomer (Fuji Ortho LC, GC Europe, Leuven, Belgium). Forty-five bovine mandibular permanent incisors were randomly divided into 3 groups; each group contained 15 teeth. Bleaching treatment was performed at 2 different times before the bonding procedure. Forty-five stainless steel brackets were bonded with the resin-modified glass ionomer. After bonding, all samples were stored in distilled water for 24 hours and then tested in shear mode on a testing machine. Group 1 (no bleaching) showed significantly higher shear bond strength values than groups 2 (bleaching immediately before bonding) and 3 (bleaching 1 week before bonding). No significant differences were found between groups 2 and 3. Moreover, no significant differences in debond locations were found among the 3 groups. Bleaching treatment before bonding significantly lowered the bond strength values of Fuji Ortho LC.


Imaging Alzheimer's disease.
Prior reviews on the topic of imaging and Alzheimer's disease have focused predominately on the technical features of imaging modalities or have summarized the results of epidemiologic studies. As brain scientists and brain practitioners, our main focus should be on the neurobiologic correlates of imaging, so we can intertwine this knowledge with our understanding of disease pathophysiology. A focus on these two features--the neurobiologic correlates of imaging and the pathophysiology of Alzheimer's disease--has provided the organizing principle of this review.


Effective and fast binarization method for combined degradation on ancient documents.
Document image binarization is a challenging task because of combined degradation in a document. In this study, a new binarization method is proposed for binarizing an ancient document with combined degradation. The proposed method comprises the following four stages: histogram analysis, contrast enhancement, local adaptive thresholding, and artifact removal. In histogram analysis, a new approach is applied to establish a uniform background. Next, the image contrast is enhanced using a new contrast enhancement, and then the document is binarized using a novel local adaptive thresholding. Artifacts from the binarization process are removed in the artifact removal stage. Finally, an experiment is conducted using one private and four public datasets and by simulating the proposed method with and without contrast enhancement. The results showed that the proposed method is faster and more effective compared to other state-of-the-art procedures for binarizing ancient documents.


Parenteral calcitriol for treatment of severe renal osteodystrophy in children with chronic renal insufficiency.
Renal osteodystrophy is a common and incapacitating complication of chronic renal failure in children. Standard therapy with oral calcium supplements, phosphate binders, and vitamin D preparations is often inadequate to control progressive bone disease. We report the use of parenteral calcitriol therapy in two children, aged 2 and 15 years, respectively, with chronic renal failure. This treatment effectively suppressed secondary hyperparathyroidism in both patients, causing a nearly 50% reduction in circulating parathyroid hormone level and a parallel decline in serum alkaline phosphatase activity. In the younger patient, therapy was associated with healing of subperiosteal bone resorption and accelerated growth velocity. These findings indicate that parenteral administration of calcitriol may be an effective treatment option in some patients with refractory renal osteodystrophy and secondary hyperparathyroidism.


Gay and Bisexual Men's Recommendations for Effective Digital Social Marketing Campaigns to Enhance HIV Prevention and Care Continuity.
Because use of geosocial-networking smartphone applications ('apps') is ubiquitous among men who have sex with men (MSM), online-to-offline service models that include advertisements on these apps may improve engagement with effective HIV prevention and treatment services. Through our formative qualitative study, we conducted individual in-depth interviews (n = 30) and focus group discussions (n = 18) with MSM in Rhode Island to develop a digital social marketing campaign aimed at increasing HIV testing, including how best to reach men by advertising on apps. Qualitative data analysis revealed that participants were frequently exposed to pop-up advertisements on apps. These advertisements are viewed as invasive and, as such, many expressed a preference for other formats (e.g., direct messages, banner advertisements). Men expressed a preference for provocative images and phrases to catch their attention followed with fact-driven messaging to motivate them to engage with services offline. Findings from this study offer several practical recommendations for developing a social marketing campaign that uses advertisements on apps to increase HIV testing among MSM, including using formats other than pop-up advertisements and pairing fact-driven messaging with eye-catching images to direct them to trusted local clinical services.


Erratum: Management Guidelines for Metal-on-metal Hip Resurfacing Arthroplasty: A Strategy on Followup.
[This corrects the article on p. 414 in vol. 51, PMID: 28790470.].


An economical electrocoagulation process of a hazardous anionic azo dye wastewater with the combination of recycled electrodes and solar energy.
The energy and electrode costs are the restrictions of applying electrocoagulation (EC) in wastewater treatment and many attempts have been made to decrease these costs. In this study, an economical EC was investigated to treat a hazardous anionic azo dye wastewater (DW) that threatens the environment and human health. Firstly, an electrode for EC process was produced from recycled aluminum cans (RACs) by remelting in an induction melting furnace. The performance of the RAC electrodes in the EC was evaluated for COD, color removal, and the EC operating parameters such as initial pH, current density (CD), and electrolysis time. Response surface methodology which is based on central composite design (RSM-CCD) was used for the optimization of the process parameters which were found to be pH 3.96, CD 15 mA/cm2, and electrolysis time 45 min. The maximum COD and color removal values were determined as 98.87% and 99.07%, respectively. The characterization of electrodes and the EC sludge was conducted by XRD, SEM, and EDS analyses for the optimum variables. In addition, the corrosion test was conducted to determine the theoretical lifetime of the electrodes. The results showed that the RAC electrodes show an extended lifetime as compared to their counterparts. Secondly, the energy cost required to treat DW in the EC was aimed to decrease by using solar panels (PV), and the optimum number of PV for the EC was determined by the MATLAB/Simulink. Consequently, the EC with low treatment cost was proposed for the treatment of DW. An economical and efficient EC process for waste management and energy policies was investigated in the present study which will be instrumental in the emergence of new understandings.


The effects of hormonal contraceptive use on sleep in women: A systematic review and meta-analysis.
Hormonal contraceptives are some of the most widely used medications worldwide, but studies on their effects on sleep are contradictory, with some reporting a sleep-promoting effect, while others a sleep-inhibiting effect. Our objective was, therefore, to undertake a systematic review and meta-analysis of the literature on this subject to try to clarify their effects. A search was conducted in three databases (PubMed, Scopus and Web of Science). Only studies evaluating hormonal contraception use were considered eligible, and both objective and subjective sleep-related outcomes were considered. Individual effect size was calculated for each article, and meta-analyses were performed using a DerSimonian and Laird random effects method. The initial search identified 2076 articles, of which 13 met the criteria for the study after full text evaluation. A total of 33 meta-analyses were performed, three of them related to subjective measures and 30 considering data from polysomnography. The only statistically significant result between contraceptive users and non-contraceptive users was observed in respect of wake after sleep onset, which was 7 min shorter among contraceptive users (-7.12 [-12.80; -1.44]; I2 = 65%; p = 0.01). In conclusion, hormonal contraceptives are not associated with clinically relevant changes in sleep patterns in women.


Auricular enlargement: an atypical presentation of old world cutaneous leishmaniasis.
The auricle is an extremely rare site for cutaneous leishmaniasis (CL) in Old World, which tends to be a benign disease with self-healing small nodules such as the "oriental sore". However, in the New World, there is a type of CL of the ear, named as "chiclero's ulcer" which is caused by Leishmania mexicana. Herein, we describe a case of massive auricular enlargement due to Old World CL.


Induction of tolerance to islet xenografts in a concordant rat-to-mouse model.
Induction of tolerance to concordant rat islet xenografts (150 Wistar-Furth [WF] islets) in streptozocin-induced (STZ) diabetic mice (C57BL/6) was determined at three different sites for islet implantation (thymus, kidney capsule, and liver). Islets transplanted into the thymus or kidney capsule were either fresh or cultured at 24 degrees C for 7 days, and the mice received a single injection of either anti-mouse lymphocyte serum (MALS) alone or anti-rat lymphocyte serum (RALS) and MALS. Islets transplanted into the liver via the portal vein were cultured at 24 degrees C for 7 days, and the mice received a single injection of MALS and RALS. To document the induction of tolerance, recipients with islet xenografts surviving > 100 days were made diabetic again by STZ (thymus and liver) or nephrectomy (kidney capsule) and received a second transplant of 150 fresh WF islets in the kidney capsule. Kidney capsule placement of fresh or cultured islets with MALS alone or MALS and RALS did not induce tolerance in a significant number of recipients. The intrathymic transplantation of fresh or cultured islets with MALS alone resulted in prolonged WF islet xenograft survival (mean survival time of 39.7 +/- 7.9 days) but did not result in tolerance, whereas the administration of MALS and RALS with the intrathymic placement of fresh or cultured islets induced tolerance in approximately 50% of the mice. Intrahepatic transplantation of cultured islets with MALS and RALS resulted in tolerance to donor islets in 90% of the recipients. Donor specificity was evaluated by a third major histocompatibility complex-disparate fresh Lewis islet xenograft.(ABSTRACT TRUNCATED AT 250 WORDS)


Composite learning sliding mode synchronization of chaotic fractional-order neural networks.
In this work, a sliding mode control (SMC) method and a composite learning SMC (CLSMC) method are proposed to solve the synchronization problem of chaotic fractional-order neural networks (FONNs). A sliding mode surface and an adaptive law are constructed to update parameter estimation. The SMC ensures that the synchronization error asymptotically tends to zero under a strict permanent excitation (PE) condition. To reduce its rigor, online recording data together with instantaneous data is used to define a prediction error about the uncertain parameter. Both synchronization error and prediction error are used to construct a composite learning law. The proposed CLSMC method can ensure that the synchronization error asymptotically approaches zero, and it can accurately estimate the uncertain parameter. The above results obtained in the CLSMC method only requires an interval-excitation (IE) condition which can be easily satisfied. Finally, comparative results reveal the control effects of the two proposed methods.


Myelopoiesis and erythropoiesis of bone marrow cells cultured in vitro in patients recovered from aplastic anaemia.
Methylcellulose culture assay was used to detect committed haemopoietic stem cells, CFU-C and CFU-E, in aplastic anaemia patients with autologous haemopoietic reconstitution. Severe diminution of CFU-C was found in all the patients studied and the absence of a dose-response to colony stimulating factor (CSF) was demonstrated. A reduced number of CFU-E and lower erythropoietin (Ep) sensitivity of those progenitors was detected as well. Autologous serum added to the bone marrow cultures of these patients enhanced the growth of CFU-C but inhibited CFU-E growth. According to the results presented, some residual damage at the stem cell level is suggested.


TIGIT Expression on Activated NK Cells Correlates with Greater Anti-Tumor Activity but Promotes Functional Decline upon Lung Cancer Exposure: Implications for Adoptive Cell Therapy and TIGIT-Targeted Therapies.
Treatments targeting TIGIT have gained a lot of attention due to strong preclinical and early clinical results, particularly with anti-PD-(L)1 therapeutics. However, this combination has failed to meet progression-free survival endpoints in phase III trials. Most of our understanding of TIGIT comes from studies of T cell function. Yet, this inhibitory receptor is often upregulated to the same, or higher, extent on NK cells in cancers. Studies in murine models have demonstrated that TIGIT inhibits NK cells and promotes exhaustion, with its effects on tumor control also being dependent on NK cells. However, there are limited studies assessing the role of TIGIT on the function of human NK cells (hNK), particularly in lung cancer. Most studies used NK cell lines or tested TIGIT blockade to reactivate exhausted cells obtained from cancer patients. For therapeutic advancement, a better understanding of TIGIT in the context of activated hNK cells is crucial, which is different than exhausted NK cells, and critical in the context of adoptive NK cell therapeutics that may be combined with TIGIT blockade. In this study, the effect of TIGIT blockade on the anti-tumor activities of human ex vivo-expanded NK cells was evaluated in vitro in the context of lung cancer. TIGIT expression was higher on activated and/or expanded NK cells compared to resting NK cells. More TIGIT+ NK cells expressed major activating receptors and exerted anti-tumor response as compared to TIGIT- cells, indicating that NK cells with greater anti-tumor function express more TIGIT. However, long-term TIGIT engagement upon exposure to PVR+ tumors downregulated the cytotoxic function of expanded NK cells while the inclusion of TIGIT blockade increased cytotoxicity, restored the effector functions against PVR-positive targets, and upregulated immune inflammation-related gene sets. These combined results indicate that TIGIT blockade can preserve the activation state of NK cells during exposure to PVR+ tumors. These results support the notion that a functional NK cell compartment is critical for anti-tumor response and anti-TIGIT/adoptive NK cell combinations have the potential to improve outcomes.


Post-traumatic stress disorder and occupational characteristics of police officers in Republic of Korea: a cross-sectional study.
South Korean police officers have a greater workload compared to their counterparts in advanced countries. However, few studies have evaluated the occupational challenges that South Korean police officers face. Therefore, this study aimed to evaluate the police officer's job characteristics and risk of post-traumatic stress disorder (PTSD) among South Korean police officers. Cross-sectional study. Police officers in South Korea. 3817 police officers with a traumatic event over a 1-year period. Officers with a response to the Impact of Event Scale (revised Korean version) score of ≥ 26 were classified as high risk, and we evaluated their age, sex, department and rank, as well as the frequency and type of traumatic events that they experienced. Among the respondents, 41.11% were classified as having a high risk of PTSD. From the perspective of the rank, Inspector group (46.0%) and Assistant Inspector group (42.7%) show the highest frequencies of PTSD. From the perspective of their working division, Intelligence and National Security Division (43.6%) show the highest frequency, followed by the Police Precinct (43.5%) and the Traffic Affairs Management Department (43.3%). It is shown that working in different departments was associated with the prevalence of PTSD (p=0.004). The high-risk classification was observed in 41.11% of all officers who had experienced traumatic events, and this frequency is greater than that for other specialised occupations (eg, firefighters). Therefore, we conclude that groups with an elevated proportion of high-risk respondents should be a priority for PTSD treatment, which may help increase its therapeutic effect and improve the awareness of PTSD among South Korean police officers.


Cytotoxic effects of dexamethasone restricted to noncycling, early G1-phase cells of L1210 leukemia.
The cytostatic and cytolytic effects of dexamethasone were studied as functions of cell cycle position in mouse L1210 leukemia cells. To this end, the cells were separated according to size by sedimentation at unit gravity in a specially designed sedimentation chamber. The fractions were analyzed by radioautography and flow cytophotometry. The size-distributions obtained by 1g sedimentation coincided with cell-cycle age distribution. With increasing fraction number, samples highly enriched in G1, S, and G2/M cells, respectively were obtained: the smallest cells being in early G1 and the largest in mitosis. In the presence of dexamethasone (10(-6)-10(-5) M), growth slowed down after a few cell cycles and the cells accumulated in early G1 phase. Lytic cell kill by continued exposure to the drug was confined to the fractions containing the small, early G1-phase cells. These fractions were also enriched in noncycling cells that were not labeled by prolonged exposure to 3H-thymidine. After removal of dexamethasone, the cells in S and G2/M phase completed cell cycle traverse but were retarded again in the G1 and early S phase of the next division cycle. The data suggest a memory effect for previous drug exposure. It is concluded that the cytostatic and cytolytic effects of dexamethasone are separate, though not unrelated events. Cytolysis is confined to the noncycling cells that in untreated populations can exit from the dividing compartment during a transitional phase of about 60 minutes subsequent to mitotic division. The cytostatic effects potentiate cytolysis by accumulating the cells in the early G1 phase and thus increasing the probability of their transit to the G0 compartment, sensitive for drug-mediated cytolysis.


A large lipoma of the ascending aorta.
Ascending aortic tumors are extremely rare. We describe a patient with a large lipoma of the ascending aorta, which was discovered after opening the pericardium for a surgical procedure for mitral regurgitation due to prolapse.


Clinical and morphological diagnosis of cardiac AL amyloidosis: a review of findings and difficulties as illustrated in one case.
Primary amyloid light-chain (AL) amyloidosis results from plasma cell dyscrasia. Fibrillar deposits of monoclonal immunoglobulin light chains are present in various organs, especially in the heart. The patients suffer from fatal cardiac dysfunction. We report the case of a 54-year-old man with symptoms of cardiac arrhythmia which was refractory to conventional treatment and ablations. At a later stage of his disease, the diagnosis of AL amyloidosis associated with monoclonal gammapathy of uncertain significance was established. Echocardiography, electrocardiography, serum immunofixation studies, abdominal fat aspirate biopsy, and bone marrow biopsy indirectly confirmed the diagnosis of cardiac amyloidosis. The patient died. The diagnosis of AL cardiac amyloidosis is difficult, the prognosis always serious, the available therapy limited, and the mortality high.


CRF-5-HT interactions in the dorsal raphe nucleus and motivation for stress-induced opioid reinstatement.
The serotonin (5-hydroxytryptamine, 5-HT) system plays an important role in stress-related psychiatric disorders and substance abuse. Our previous data show that stressors can inhibit 5-HT neuronal activity and release by stimulating the release of the stress neurohormone corticotropin-releasing factor (CRF) within the serotonergic dorsal raphe nucleus (DRN). The inhibitory effects of CRF on 5-HT DRN neurons are indirect, mediated by CRF-R1 receptors located on GABAergic afferents. We tested the hypothesis that DRN CRF-R1 receptors contribute to stress-induced reinstatement of morphine-conditioned place preference (CPP). We also examined the role of this circuitry in stress-induced negative affective state with 22-kHz distress ultrasonic vocalizations (USVs), which are naturally emitted by rats in response to environmental challenges such as pain, stress, and drug withdrawal. First, we tested if activation of CRF-R1 receptors in the DRN with the CRF-R1-preferring agonist ovine CRF (oCRF) would reinstate morphine CPP and then if blockade of CRF-R1 receptors in the DRN with the CRF-R1 antagonist NBI 35965 would attenuate swim stress-induced reinstatement of morphine CPP. Second, we tested if intra-DRN pretreatment with NBI 35965 would attenuate foot shock stress-induced 22-kHz USVs. Intra-DRN injection of oCRF reinstated morphine CPP, while intra-DRN injection of NBI 35965 attenuated swim stress-induced reinstatement. Moreover, intra-DRN pretreatment with NBI 35965 significantly reduced 22-kHz distress calls induced by foot shock. These data provide evidence that stress-induced negative affective state is mediated by DRN CRF-R1 receptors and may contribute to reinstatement of morphine CPP.


Time-dependent analysis of incidence, risk factors and clinical significance of pneumothorax after percutaneous lung biopsy.
To evaluate the time-dependent incidence, risk factors and clinical significance of percutaneous lung biopsy (PLB)-related pneumothorax. From January 2012-November 2015, 3,251 patients underwent 3,354 cone-beam CT-guided PLBs for lung lesions. Cox, logistic and linear regression analyses were performed to identify time-dependent risk factors of PLB-related pneumothorax, risk factors of drainage catheter insertion and those of prolonged catheter placement, respectively. Pneumothorax occurred in 915/3,354 PLBs (27.3 %), with 230/915 (25.1 %) occurring during follow-ups. Risk factors for earlier occurrence of PLB-related pneumothorax include emphysema (HR=1.624), smaller target (HR=0.922), deeper location (HR=1.175) and longer puncture time (HR=1.036), while haemoptysis (HR=0.503) showed a protective effect against earlier development of pneumothorax. Seventy-five cases (8.2 %) underwent chest catheter placement. Mean duration of catheter placement was 3.2±2.0 days. Emphysema (odds ratio [OR]=2.400) and longer puncture time (OR=1.053) were assessed as significant risk factors for catheter insertion, and older age (parameter estimate=1.014) was a predictive factor for prolonged catheter placement. PLB-related pneumothorax occurred in 27.3 %, of which 25.1 % developed during follow-ups. Smaller target size, emphysema, deeply-located lesions were significant risk factors of PLB-related pneumothorax. Emphysema and older age were related to drainage catheter insertion and prolonged catheter placement, respectively. • One-fourth of percutaneous lung biopsy (PLB)-related pneumothorax occurs during follow-up. • Smaller, deeply-located target and emphysema lead to early occurrence of pneumothorax. • Emphysema is related to drainage catheter insertion for PLB-related pneumothorax. • Older age may lead to prolonged catheter placement for PLB-related pneumothorax. • Tailored management can be possible with time-dependent information of PLB-related pneumothorax.


The association of Raynaud's syndrome with carpal tunnel syndrome: a meta-analysis.
Carpal tunnel syndrome (CTS) has traditionally been included among the diseases associated with Raynaud's syndrome (RS). The prevalence of RS in patients suffering from CTS is not well defined. The objective of this paper was to assess the prevalence of RS in patients with CTS-a meta-analysis of published data was performed. The PubMed database of the National Library of Medicine and ISI Web of Knowledge was used for studies dealing with RS and CTS. The studies provided sufficient data to estimate the prevalence of RS in patients of CTS. A forest plot was determined by the revealed prevalence. Statistical analysis was based on methods for a random effects meta-analysis and a finite mixture model for proportions. Publication bias was investigated with the linear regression test (Egger's method). A meta-regression was conducted by the year of publication. Eight eligible studies, contributing data on 675 subjects, were included in this meta-analysis. For CTS, a pooled prevalence of 15.5% and 95% CI (95% CI 0.043, 0.318) were obtained. Statistically publication bias was present (P value 0.143). A mixture model analysis found five latent classes. The meta-regression indicated that the estimated prevalence increased when the year of commencement increased, too. Within the decade (1957-1967), the odds ratio increased from 1 (95% CI 1.065, 1.112) to 2.340 (95% CI 1.886, 2.903). Despite some heterogeneity, there is a possible indication of an association between RS and patients with CTS.


Fasting in Ramadan of Muslim patients with diabetes Mellitus, and knowledge and practice in relation to diabetes control in Brunei.
To investigate the fasting pattern of patients with Diabetes Mellitus in Brunei Darussalam, specifically, their fasting activities, and knowledge and practice in relation to diabetes control during fasting in Ramadan. Cross-sectional study that included 18 years and older, Muslim patients with diabetes Mellitus who attended the main Diabetes Centre in Brunei. A self-administered questionnaire was designed, tested and used to collect the demographic information, fasting duration, knowledge and practice on diabetes control during fasting, and reasons of fasting as a Muslim. 183 participants with a mean age of 53.7 (SD 11.52) years were recruited. Prevalence of fasting during Ramadan was 93.4% with an average number of days of fasting was 24.1 days. Those with age 55 and above had significant higher prevalence of fasting than the younger group (p = 0.010). Only 49.1% of participants had consulted their healthcare professionals of their intentions to fast prior to the Ramadan, and only 38.1% of participants monitored blood glucose levels throughout the month. Diabetes education and early treatment adjustment especially before and during the month of Ramadan is essential to minimize hypoglycaemic risks and frequency of diabetes complications.


A yellow transient forms in the decomposition in acidic solution of the blue-violet nickel(II) complex of a trifurcated hexamine.
In the decomposition in acidic solution of the octahedral high-spin nickel(II) complex with the hexamine sen, a thermodynamically unstable, kinetically controlled, square-planar low-spin species forms, with a lifetime of 5 s.


Posterior segmentation of the Drosophila embryo in the absence of a maternal posterior organizer gene.
Maternal hunchback activity suppresses the genetic pathway for abdomen formation in the Drosophila embryo. The active component of the posterior group of maternal genes, nanos, acts as a specific repressor of hunchback in the posterior region. Absence of both repressors results in normal embryos, indicating that posterior segmentation may not directly require maternal determinants.


Preparation of magnetic core-mesoporous shell microspheres with C8-modified interior pore-walls and their application in selective enrichment and analysis of mouse brain peptidome.
In this paper, magnetic mesoporous silica microspheres with C8-modified interior pore-walls were prepared through a facile one-pot sol-gel coating strategy, and were successfully applied for selective enrichment of endogenous peptides in mouse brain for peptidome analysis. Through the one-pot sol-gel approach with surfactant (CTAB) as a template, tetraethyl orthosilicate (TEOS) and n-ctyltriethoxysilane (C8TEOS) as the precursors, C8-modified magnetic mesoporous microspheres (C8-Fe(3)O(4)@mSiO(2)) consisting magnetic core and mesoporous silica shell with C8-groups exposed in the mesopore channels were synthesized. The obtained microspheres possess highly open mesopores of 3.4 nm, high surface area (162.5 m(2)/g), large pore volume (0.17 cm(3)/g), excellent magnetic responsivity (56.3 emu/g) and good dispersibility in aqueous solution. Based on the abundant surface silanol groups, functional C8 groups and the strong magnetic responsivity of the core-shell C8-Fe(3) O(4) @mSiO(2) microspheres, efficient and fast enrichment of peptides was achieved. Additionally, the C8-Fe(3)O(4)@mSiO(2) microspheres exhibit excellent performance in selective enrichment of endogenous peptides from complex samples that are consist of peptides, large proteins and other compounds, including human serum and mouse brain followed by automated nano-LC-ESI-MS/MS analysis. These results indicate C8-Fe(3)O(4)@mSiO(2) microspheres would be a potential candidate for endogenous peptides enrichment and biomarkers discovery in peptidome analysis.


Transfusion-free complex cardiac surgery with cardiopulmonary bypass in a 3.55-kg Jehovah's Witness neonate.
Complex cardiac surgery using cardiopulmonary bypass normally requires the transfusion of autologous blood components, particularly in neonates. This is predominately caused by the relatively high priming volume of the circuit with subsequent extreme hemodilution and the often extended and complex perfusions leading to progressive consumption of platelets and coagulation factors. We report on a strategy to minimize the cardiopulmonary bypass circuit and adjust the perfusion technique that resulted in transfusion-free correction of tetralogy of Fallot with an absent pulmonary valve and an aneurysm of the left pulmonary artery in a 3.55 kg Jehovah's Witness neonate boy.


The current landscape of microRNAs (miRNAs) in bacterial pneumonia: opportunities and challenges.
MicroRNAs (miRNAs), which were initially discovered in Caenorhabditis elegans, can regulate gene expression by recognizing cognate sequences and interfering with the transcriptional or translational machinery. The application of bioinformatics tools for structural analysis and target prediction has largely driven the investigation of certain miRNAs. Notably, it has been found that certain miRNAs which are widely involved in the inflammatory response and immune regulation are closely associated with the occurrence, development, and outcome of bacterial pneumonia. It has been shown that certain miRNA techniques can be used to identify related targets and explore associated signal transduction pathways. This enhances the understanding of bacterial pneumonia, notably for "refractory" or drug-resistant bacterial pneumonia. Although these miRNA-based methods may provide a basis for the clinical diagnosis and treatment of this disease, they still face various challenges, such as low sensitivity, poor specificity, low silencing efficiency, off-target effects, and toxic reactions. The opportunities and challenges of these methods have been completely reviewed, notably in bacterial pneumonia. With the continuous improvement of the current technology, the miRNA-based methods may surmount the aforementioned limitations, providing promising support for the clinical diagnosis and treatment of "refractory" or drug-resistant bacterial pneumonia.


A Method for Measuring the Directional Response of Ultrasound Receivers in the Range 0.3-80 MHz Using a Laser-Generated Ultrasound Source.
A simple method for measuring the directivity of an ultrasound receiver is described. The method makes use of a custom-designed laser ultrasound source which generates a large diameter (>1 cm) broadband monopolar plane wave with a continuous frequency content extending from to . The plane wave is highly uniform in amplitude (±5% over >8 mm) and phase (equivalent to at 80 MHz over ). To measure directivity, the source is rotated around the receiver under test in a compact centimeter-scale setup. To demonstrate the method, it was used to measure the directivity of two broadband small aperture Fabry-Perot ultrasound sensors over an angular range of ±50° at frequencies up to 80 MHz. Measurements were found to be highly repeatable with an estimated typical repeatability <4% in the range of 0.5-25 MHz. Due to the broad bandwidth, large size, and adjustable nature of the source, the method is widely applicable and could aid the characterization of receivers used in medical ultrasound, ultrasonic nondestructive testing. and ultrasound metrology.


Evidence for anthropophily in five species of phlebotomine sand flies (Diptera: Psychodidae) from northern Colombia, revealed by molecular identification of bloodmeals.
Identification of the bloodmeal sources of phlebotomine sand flies is fundamental to determining which species are anthropophilic and understanding the transmission of Leishmania parasites in natural epidemiological settings. The objective of this study was to identify sand fly bloodmeals in the mixed leishmaniasis focus of the department of Sucre, northern Colombia. In all 141 engorged female sand flies were analyzed, after being captured in intradomiciliary, peridomiciliary and extradomiciliary habitats with Shannon and CDC traps and by active searching in diurnal resting sites. Bloodmeals were identified by sequencing and analysis of a 358bp fragment of the mitochondrial gene Cytochrome b (CYB) and a 330bp fragment of the nuclear gene prepronociceptin (PNOC). Using both genes 105 vertebrate bloodmeals were identified, with an efficiency of 72% for CYB but only 7% for PNOC. Ten species of vertebrates were identified as providing bloodmeal sources for 8 sand fly species: Homo sapiens (Lutzomyia evansi, Lutzomyia panamensis, Lutzomyia micropyga, Lutzomyia shannoni and Lutzomyia atroclavata), Equus caballus (L. evansi, L. panamensis and Lutzomyia cayennensis cayennensis), Equus asinus (L. evansi and L. panamensis), Bos taurus (L. evansi, L. panamensis and L. c. cayennensis), Tamandua mexicana (L. shannoni and Lutzomyia trinidadensis), Proechimys guyanensis (L. evansi, L. panamensis and L. c. cayennensis), Mabuya sp. (Lutzomyia micropyga), Anolissp. (L. micropyga), Sus scrofa (L. evansi and Lutzomyia gomezi) and Gallus gallus (L. evansi). Cattle, donkeys, humans and pigs were significantly more important than other animals (P=0.0001) as hosts of L. evansi, this being the most abundant sand fly species. The five Lutzomyia species in which blood samples of human origin were detected included L. micropyga and L. atroclavata, constituting the first evidence of anthropophily in both species.


Tuning Interphase Chemistry to Stabilize High-Voltage LiCoO2 Cathode Material via Spinel Coating.
Cathode electrolyte interphases (CEIs) are critical to the cycling stability of high-voltage cathodes for batteries, yet their formation mechanism and properties remain elusive. Here we report that the compositions of CEIs are largely controlled by abundant species in the inner Helmholtz layer (IHL) and can be tuned from material aspects. The IHL of LiCoO2 (LCO) was found to alter after charging, with a solvent-rich environment that results in fragile organic-rich CEIs. By passivated spinel Li4 Mn5 O12 coating, we achieve an anion-rich IHL after charging, thus enabling robust LiF-rich CEIs. In situ microscopy reveals that LiF-rich CEIs maintain mechanical integrity at 500 °C, in sharp contrast to organic-rich CEIs which undergo severe expansion and subsequent voids/cracks in the cathode. As a result, the spinel-coated LCO exhibits a high specific capacity of 194 mAh g-1 at 0.05 C and a capacity retention of 83 % after 300 cycles at 0.5 C. Our work sheds new light on modulating CEIs for advanced lithium-ion batteries.


Correlation of clinical and magnetic resonance imaging findings in hips of elite female ballet dancers.
To understand why professional female ballet dancers often complain of inguinal pain and experience early hip osteoarthritis (OA). Goals were to examine clinical and advanced imaging findings in the hips of dancers compared with those in a matched cohort of nondancers and to assess the femoral head translation in the forward split position using magnetic resonance imaging (MRI). Twenty professional female ballet dancers and 14 active healthy female individuals matched for age (control group) completed a questionnaire on hip pain and underwent hip examination with impingement tests and measurement of passive hip range of motion (ROM). All had a pelvic 1.5 T MRI in the back-lying position to assess femoroacetabular morphologic features and lesions. For the dancers, additional MR images were acquired in the split position to evaluate femoroacetabular congruency. Twelve of 20 dancers complained of groin pain only while dancing; controls were asymptomatic. Dancers' passive hip ROM was normal. No differences in α neck angle, acetabular depth, acetabular version, and femoral neck anteversion were found between dancers and controls. MRI of dancers while performing splits showed a mean femoral head subluxation of 2.05 mm. MRI of dancers' hips showed labral tears, cartilage thinning, and herniation pits, located in superior and posterosuperior positions. Lesions were the same for symptomatic and asymptomatic dancers. Controls had proportionally the same number of labral lesions but in an anterosuperior position. They also had 2 to 3 times fewer cartilage lesions and pits than did dancers. The results of our study are consistent with our hypothesis that repetitive extreme movements can cause femoral head subluxations and femoroacetabular abutments in female ballet dancers with normal hip morphologic features, which could result in early OA. Pathologic changes seen on MRI were symptomatic in less than two thirds of the dancers. Level IV, therapeutic case series.


Characterization of hbzE-encoded gentisate 1,2-dioxygenase from Pseudomonas alcaligenes NCIMB 9867.
Pseudomonas alcaligenes NCIMB 9867 (strain P25X) is known to synthesize two isofunctional gentisate 1,2-dioxygenases (GDO; EC 184.108.40.206) as well as other enzymes involved in the degradation of xylenols and cresols via the gentisate pathway. The hbzE gene encoding what is possibly the strictly inducible gentisate 1,2-dioxygenase II (GDO-II) was cloned, overexpressed and purified as a hexahistidine fusion protein from Escherichia coli. Active recombinant GDO-II had an estimated molecular mass of 150kDa and is likely a tetrameric protein with a subunit mass of approximately 40kDa, similar to the previously characterized gentisate 1,2-dioxygenase I (GDO-I) encoded by xlnE. However, GDO-II was unable to utilize gentisate that is substituted at the carbon-4 position, unlike GDO-I which had broader substrate specificity. GDO-II also possessed different kinetic characteristics when compared to GDO-I. The hbzE-encoded GDO-II shared higher sequence identities (53%) with GDOs from Ralstonia sp. U2 and Polaromonas naphthalenivorans CJ2, compared with only 35% identity with the xlnE-encoded GDO-I. The hbzE gene was found to be part of a cluster of nine genes including the putative regulatory gene designated hbzR, which encodes an LysR-type regulator and is divergently transcribed from the other genes of the hbzHIJKLFED cluster.


Prediction Model for Job Retention According to the Type of Return to Work Among Industrially Injured Workers in Korea.
This study aimed to investigate how the type of return to work after an industrial accident affects job retention. Using data from the panel study of workers' compensation insurance first-third, and hazard ratios (HRs) and 95% confidence intervals were calculated for workers leaving their jobs. The HR leaving their jobs were higher in the "reemployed" compared with that in the "returned to original work," with HR of 2.69 (2.33-3.10). According workers' status, the HRs leaving their jobs were higher among the "reemployed" than among those who "returned to original work." Regular and daily workers' HRs were 1.70 (1.37-2.11) and 3.55 (2.96-4.26), respectively. The findings suggest that to increase job retention rate, protection policies for reemployed workers or support for employers who hire reemployed workers should be considered.


Comparison of acute toxicity and mortality after two different dosing regimens of high-dose interleukin-2 for patients with metastatic melanoma.
We compared acute toxicity, drug exposure, in-hospital mortality, and inpatient length of stay between two currently recommended dosing protocols (from the National Comprehensive Cancer Network Guidelines) of high-dose interleukin-2 (IL-2) treatment for patients with metastatic melanoma. Patients with metastatic melanoma who received high-dose IL-2 treatment between 2003 and 2010 were identified. Chemotherapy orders, electronic medical records, paper medical charts, and patient discharge summaries were reviewed retrospectively. We identified 13 patients who had received 600,000 units/kilogram (kg)/dose and 15 patients who had received 720,000 units/kg/dose. Patients in the 720,000 units/kg/dose group had a higher rate of grade 3 and 4 bilirubin elevations (34 vs. 12 %), weight gain (any grade, 96 vs. 89 %), and thrombocytopenia (any grade, 75 vs. 65 %). Patients receiving the higher dose also experienced more dose-limiting neurotoxicity (45 vs. 23 %), large-volume diarrhea (15 vs. 0 %), and hepatotoxicity (7 vs. 0 %). There was no in-hospital mortality during treatment in either group. The average length of stay was similar between both groups (5 days, SD = 1 for both groups), and the median cumulative IL-2 exposure was similar between both groups for the first course (10.1 vs.10.5 million units/kg) and for all courses (approximately 11-12 million units/kg). Both high-dose IL-2 protocols had comparable in-hospital mortality and cumulative IL-2 exposure. The 720,000 units/kg/dose dosing scheme did not shorten the length of stay but did lead to greater acute toxicity. Therefore, as a result, we recommend 600,000 units/kg/dose when deciding between the two regimens.


Overcoming the Data Gap for the Remote Diagnosis of Skin Cancer.
The use of AI algorithms for categorizing medical images has become very popular and critical in the diagnosis of various diseases. Current computer-aided diagnosis (CAD) systems are hugely dependent on good quality, well-annotated data captured by professional medical equipment. In many remote areas, a lack of medical equipment and medical specialists that are respectively necessary for producing good quality data and annotating data, have caused a data gap and has resulted in no possibility of using CAD systems in those areas. Here, I point out other sources of data by previewing a recently published dataset that could help resolve this worldwide issue.


The metalloproteolytic activity of the anthrax lethal factor is substrate-inhibited.
The anthrax lethal factor (LF) is a Zn2+ endopeptidase specific for mitogen-activated protein kinase kinases (MAPKKs), which are cleaved within their N termini. Here, the proteolytic activity of LF has been investigated using novel chromogenic MAPKK-derived peptide substrates, which allowed us to determine the kinetic parameters of the reaction. LF displayed maximal proteolytic activity at the pH and temperature values of the cell cytosol, which is its site of action. LF undergoes substrate inhibition, in keeping with the non-productive binding geometry of the MAPPK-2 N terminus to LF.


Endoscopic laser resection of atherosclerotic plaque in a live animal model. A preliminary report on some technical difficulties.
This study was designed to determine whether laser energy could be used effectively to resect atherosclerotic plaque through an endoscope in a live animal model. Twelve adult Yorkshire swine with infrarenal aortic atherosclerosis had a 2.5 mm and/or 3.2 mm diameter fiberscope passed into the aorta from the femoral artery after proximal aortic balloon occlusion. Endoscopic argon laser resection of the atherosclerotic plaque was then attempted in eight pigs with an argon laser fiber (60 to 400 microns). We were able to visualize the raised atherosclerotic plaque in all 12 pigs with the larger 3.2 mm diameter fiberscope, which was easily passed into the aortoiliac system from the 4 mm diameter femoral vessel. The articulating end feature enhanced maneuverability within the lumen and allowed laser fiber direction. The 2.5 mm endoscope did not allow adequate visualization in any pig since the vessel could not be cleared of blood. The 2.5 mm endoscope was also passed from the femoral artery distally into the hind limb and still did not allow adequate visualization of the vessel wall because of persistent luminal blood. The 3.2 mm endoscope enabled vessel wall visualization distal to the femoral artery when the proximal artery was occluded. No aortas were grossly perforated by the laser energy. In all pigs undergoing endoscopic laser resection, raised plaques were removed both grossly and histologically, although the plaque edges were carbonized and frayed as well as vaporized. With the small spot size of the argon fiber, channels were drilled through plaque, frequently with incomplete recanalization of the lumen.(ABSTRACT TRUNCATED AT 250 WORDS)


Therapy of basal cell carcinoma--treatment in 1980-81 compared with 1985-86 and advantages of shave excision for smaller tumours.
A survey of basal cell carcinoma treatments in two 12-month periods, 1980-81 and 1985-86, revealed that more tumours and an older age group of patients were presenting to the Lancaster dermatology department in the latter period. Whereas the most frequent surgical treatment in 1980-81 was curettage and cautery, shave excision and cautery was the treatment of choice in 1985-86. Shave excision is quick, easy to perform and gives good specimens for histological assessment. The method is suitable for smaller tumours but not for more difficult tumours or tumours in difficult sites.


Synthesis and release of gonadotropins and their subunits by long-term organ cultures of human fetal hypophyses.
From weeks 13 to 26 of fetal life human hypophyses disclosed a constant content of radioimmunoassayable FSH. Although present already before this period, LH content increased considerably at week 17, along with the appearance of free beta-LH. In long-term organ culture experiments such early differentiating pituitaries proved to be endowed with autonomous synthesis and release of FSH and of free alpha-subunit, while LH, beta-LH and TSH declined to very low levels within a few weeks. Supplementation of the medium with LH-RH (12 ng/ml) significantly increased FSH synthesis and release but was not sufficient to sustain production of beta-LH and LH. It is suggested that other factors than LH-RH are required for differentiation of beta-LH biosynthesis and thus for production of LH.


Prenatal phenotyping of fetal tubulinopathies: A multicenter retrospective case series.
Tubulinopathies refer to conditions caused by genetic variants in isotypes of tubulin resulting in defective neuronal migration. Historically, diagnosis was primarily via postnatal imaging. Our objective was to establish the prenatal phenotype/genotype correlations of tubulinopathies identified by fetal imaging. A large, multicenter retrospective case series was performed across nine institutions in the Fetal Sequencing Consortium. Demographics, fetal imaging reports, genetic screening and diagnostic testing results, delivery reports, and neonatal imaging reports were extracted for pregnancies with a confirmed molecular diagnosis of a tubulinopathy. Nineteen pregnancies with a fetal tubulinopathy were identified. The most common prenatal imaging findings were cerebral ventriculomegaly (15/19), cerebellar hypoplasia (13/19), absence of the cavum septum pellucidum (6/19), abnormalities of the corpus callosum (6/19), and microcephaly (3/19). Fetal MRI identified additional central nervous system features that were not appreciated on neurosonogram in eight cases. Single gene variants were reported in TUBA1A (13), TUBB (1), TUBB2A (1), TUBB2B (2), and TUBB3 (2). The presence of ventriculomegaly with cerebellar abnormalities in conjunction with additional prenatal neurosonographic findings warrants additional evaluation for a tubulinopathy. Conclusive diagnosis can be achieved by molecular sequencing, which may assist in coordination, prognostication, and reproductive planning.


Mechanism-based therapeutic approaches to cachexia.
Cachexia is a multifactorial syndrome characterized by body weight loss, depletion of adipose tissue and skeletal muscle mass, and marked alterations in the metabolic homeostasis. The occurrence of cachexia significantly impinges on patients' morbidity and mortality, and on quality of life. Inflammation, anorexia/malnutrition, alterations of protein and lipid metabolism are among the main mechanisms involved in the development of cachexia. While anorexia and malnutrition have long been known to be contributing factors, the mechanisms leading to inflammation and metabolic alterations were clarified much later. On these premises, several therapeutic approaches were proposed. Most of them are in the preclinical phase, but some have already reached the clinical experimentation stage. This review focuses on treatment options proposed on the basis of mechanistic alterations. In this regard, in addition to nutritional and anti-inflammatory strategies, approaches based on perturbation of specific signal transduction pathways are taken into consideration.


Correlation between lncRNA SNHG16 gene polymorphism and its interaction with environmental factors and susceptibility to colorectal cancer.
To study the relationship between long-chain non-coding RNA small nucleolar RNA host gene 16 (lncRNA SNHG16) polymorphisms and its interaction with environmental factors and susceptibility to colorectal cancer (CRC). Sanger sequencing was used to analyze genotypes of lncRNA SNHG16 gene rs7353, rs8038, and rs15278 sites. Multifactor dimensionality reduction was used to analyze interactions between lncRNA SNHG16 gene rs7353, rs8038, rs15278 sites, and environmental factors. Haploview 4.1 software was used to analyze linkage disequilibrium of lncRNA SNHG16 gene rs7353, rs8038, and rs15278 sites. Quantitative real-time polymerase chain reaction was used to analyze plasma lncRNA SNHG16 levels of CRC patients and control subjects. Variation of the lncRNA SNHG16 gene rs7353 site A>G variation was associated with decreased CRC susceptibility (Odds ratio [OR] = 0.50, 95% confidence interval [CI]: 0.40-0.62, P < .01). The rs8038 site G>A and rs15278 site A>G variation were associated with increased CRC susceptibility (OR = 1.87, 95% CI: 1.47-2.36, P < .01). The rs15278 site G>A variation was associated with increased CRC susceptibility (OR = 2.24, 95% CI: 1.61-3.11, P < .01). Interaction combinations featuring age, rs7353, rs8038, and rs15278 single nucleotide polymorphism are 13.53 times more susceptible to CRC than other interactions (95% CI: 9.43-19.41, P < .01). The rs15278, rs8038, and rs7353 site AGA haplotypes were significantly associated with a decreased CRC risk (OR = 0.65, 95% CI: 0.48-0.88, P = .01), AAG haplotypes were significantly associated with an increased CRC risk (OR = 2.00, 95% CI: 1.27-3.17, P < .01). High lncRNA SNHG16 expression was associated with tumor progression in CRC patients (χ = 8.85, P = .03). The rs7353 site A>G variation caused a significant decrease in plasma lncRNA SNHG16 level (P < .01), while the rs8038 site G>A variation and rs15278 site A>G variation resulted in increased plasma lncRNA SNHG16 levels. Polymorphisms of lncRNA SNHG16 gene rs7353, rs8038, rs15278 loci and their interaction with age are significantly associated with CRC susceptibility.


Synthesis and biological evaluation of 4β-sulphonamido and 4β-[(4'-sulphonamido)benzamide]podophyllotoxins as DNA topoisomerase-IIα and apoptosis inducing agents.
A series of new 4β-sulphonamido and 4β-[(4'-sulphonamido)benzamide] conjugates of podophyllotoxin (11a-j and 15a-g) were synthesized and evaluated for anticancer activity against six human cancer cell lines and found to be more potent than etoposide. Some of the compounds 11b, 11d and 11e that showed significant antiproliferative activity in Colo-205 cells, were superior to etoposide. The flow cytometric analysis indicates that these compounds (11b, 11d and 11e) showed G2/M cell cycle arrest and among them 11e is the most effective. It is observed that this compound (11e) caused both single-strand DNA breaks as observed by comet assay as well as double-strand DNA breaks as indicated by γ-H2AX. Further 11e showed inhibition of topo-IIα as observed from Western blot analysis and related studies. Compounds caused activation of ATM as well as Chk1 protein indicating that the compound caused effective DNA damage. Moreover activation of caspase-3, p21, p16, NF-kB and down regulation of Bcl-2 protein suggests that this compound (11e) has apoptotic cell death inducing ability, apart from acting as a topo-IIα inhibitor.


Design of an inductively decoupled microstrip array at 9.4 T.
By independent control of the phases and amplitudes of its elements, the microstrip transmission-line array can mitigate sample-induced RF non-uniformities, and has been widely used as the transceiver in parallel imaging applications. One major challenge in implementing the microstrip array is the reduction of mutual coupling among individual elements. The low-input impedance preamplifier is commonly used for the decoupling purpose. However, it is impractical in the transceiver array design. Although interconnecting capacitors can be utilized to reduce the mutual coupling, they only efficiently work for the neighbor elements. In addition, this approach is impractical at fields higher than 300 MHz, in which the required decoupling capacitance is commonly less than 0.5 pF. We propose a novel decoupling approach by using decoupling inductors in this study. Due to the fact that the decoupling inductance is independent of the resonant frequency, the microstrip arrays can be well decoupled at ultra-high fields. To verify the proposed approach, an eight-channel microstrip array is fabricated and tested at 9.4 T. For this prototype, couplings between elements are significantly reduced by using the interconnecting inductors. The phantom experiment shows that the inductively decoupled microstrip array has good parallel imaging performance.


Dispersal of Arbuscular Mycorrhizal Fungi: Evidence and Insights for Ecological Studies.
Dispersal is a critical ecological process that modulates gene flow and contributes to the maintenance of genetic and taxonomic diversity within ecosystems. Despite an increasing global understanding of the arbuscular mycorrhizal (AM) fungal diversity, distribution and prevalence in different biomes, we have largely ignored the main dispersal mechanisms of these organisms. To provide a geographical and scientific overview of the available data, we systematically searched for the direct evidence on the AM fungal dispersal agents (abiotic and biotic) and different propagule types (i.e. spores, extraradical hyphae or colonized root fragments). We show that the available data (37 articles) on AM fungal dispersal originates mostly from North America, from temperate ecosystems, from biotic dispersal agents (small mammals) and AM fungal spores as propagule type. Much lesser evidence exists from South American, Asian and African tropical systems and other dispersers such as large-bodied birds and mammals and non-spore propagule types. We did not find strong evidence that spore size varies across dispersal agents, but wind and large animals seem to be more efficient dispersers. However, the data is still too scarce to draw firm conclusions from this finding. We further discuss and propose critical research questions and potential approaches to advance the understanding of the ecology of AM fungi dispersal.


Haemaphysalis juxtakochi Cooley (Acari: ixodidae), a neotropical tick species, found in Ohio.
Haemaphysalis juxtakochi Cooley, 1946, an ectoparasite of deer and other large mammals from Mexico southward through Central and South America, was recovered from the ear of a white-tailed deer, Odocoileus virginanus Zimmermann, in Ohio. This represents the first record of H. juxtakochi from the United States.


Three new electrophoretically normal glucose-6-phosphate dehydrogenase variants associated with congenital nonspherocytic hemolytic anemia found in Japan: G6PD Ogikubo, Yokohama, and Akita.
Three new glucose-6-phosphate dehydrogenase (G6PD) variants, which showed electrophoretically normal mobility and were associated with chronic nonspherocytic hemolytic anemia, were found in Japan. G6PD Ogikubo, found in a 17-year-old male whose red cells contained 3% of normal enzyme activity, had normal Km G6P, normal Km NADP, normal utilization of deamino-NADP, decreased heat stability, and a normal pH curve. G6PD Yokohama, characterized from a 15-year-old male, had 1.9% of normal enzyme activity, normal Km G6P, normal Km NADP, low Ki NADPH, normal utilizations of both 2-deoxy-G6P and deamino-NADP, decreased heat stability, and normal pH curve. G6PD Akita, characterized from a 56-year-old male, had an undetectably low activity when hemolysate was examined, normal Km G6P, normal Km NADP, normal Ki NADPH, normal utilizations of both 2-deoxy-G6P and deamino-NADP, decreased heat stability, and normal pH curve. The degree of hemolytic anemia was moderate to mild in all three patients.


Building global models for fat and total protein content in raw milk based on historical spectroscopic data in the visible and short-wave near infrared range.
A large set of fresh cow milk samples collected from many suppliers over a large geographical area in Russia during a year has been analyzed by optical spectroscopy in the range 400-1100 nm in accordance with previously developed scatter-based technique. The global (i.e. resistant to seasonal, genetic, regional and other variations of the milk composition) models for fat and total protein content, which were built using partial least-squares (PLS) regression, exhibit satisfactory prediction performances enabling their practical application in the dairy. The root mean-square errors of prediction (RMSEP) were 0.09 and 0.10 for fat and total protein content, respectively. The issues of raw milk analysis and multivariate modelling based on the historical spectroscopic data have been considered and approaches to the creation of global models and their transfer between the instruments have been proposed. Availability of global models should significantly facilitate the dissemination of optical spectroscopic methods for the laboratory and in-line quantitative milk analysis.