The sulfurtransferase activity and structure of rhodanese are affected by site-directed replacement of Arg-186 or Lys-249.
Two mutants of the enzyme rhodanese that replace Arg-186 with Leu (R186L) or Lys-249 with Ala (K249A) were prepared to test suggestions that these residues are involved in catalysis and structure. The predominant effect with R186L was functional, and Km for the sulfur donor, thiosulfate, increased from 3.7 mM to 73 mM with a modest decrease in Vmax (672 IU/mg to 576 IU/mg). However, K249A was virtually inactive using thiosulfate, but it was active with thiosulfonates such as p-toluene-, 2-aminoethane-, or ethanethiosulfonate, and these compounds could be demonstrated to form persulfide-substituted rhodanese. Compared with wild type enzyme, K249A had (a) reduced stability, (b) comparable secondary structure, (c) more easily exposed hydrophobic surfaces, and (d) a core structure that denatured similarly to the wild type enzyme. Thus, Arg-186 and Lys-249 are important in rhodanese catalysis, and Lys-249 is particularly critical for substrate selectivity and protein stability. Finally, the results suggest that there can be active rhodanese species in vivo that will be undetected using thiosulfate as a sulfur donor.


Analytical solution of the ideal, nonlinear model of reaction chromatography for a reaction A-->B and a parabolic isotherm.
The analytical solution of the ideal, nonlinear model of reaction chromatography for the simplest possible chemical reaction, A-->B and with a parabolic isotherm for the reagent, is derived for two types of boundary conditions, the injection of a rectangular concentration pulse of finite width (elution) and that of an instantaneous concentration jump (Riemann problem or breakthrough curve). The areas of the profiles of the reagent and of the product of the reaction are calculated in both the ideal and the nonideal cases. The effects of the nonlinear behavior of the equilibrium isotherm and of axial dispersion on the reagent profile are discussed using analytical and numerical methods.


The role of 18F-FDG PET/CT in detecting colorectal cancer recurrence in patients with elevated CEA levels.
In this study we aimed to define the success of fluorine-18 (18F) fluorodeoxyglucose (FDG) PET/computed tomography (PET/CT) in detecting recurrent disease in our patient group with colorectal cancer (CRC) and elevated carcinoembryonic antigen (CEA) levels. Patients who had a previous diagnosis of CRC were searched retrospectively in our PET center database. Seventy-six 18F-FDG PET/CT studies between October 2006 and December 2010 of 69 patients (25 women, 44 men; mean age: 61.61 ± 4.1 years) with elevated CEA levels were evaluated. 18F-FDG PET/CT findings and concurrent abdominopelvic contrast-enhanced computed tomography (ceCT) findings were compared with histopathological findings and/or clinical follow-up data as the 'gold standard'. In the patient-based analysis, the sensitivity and specificity of 18F-FDG PET/CT in the detection of disease recurrence were calculated as 97 and 61%, respectively. A statistically significant difference was found in frequencies of positive and negative 18F-FDG PET/CT findings between patients with or without recurrent disease by gold standard (P<0.05). There was no correlation between patients' serum CEA levels and lesions' maximum standardized uptake values (P=0.85). The sensitivity and specificity of ceCT were computed as 51 and 60%, respectively. In the evaluation of separate patient groups, although the sensitivity and specificity of 18F-FDG PET/CT were calculated as 100 and 60% in the group whose CEA level elevation was less than two-fold (5-9.9 ng/ml), these were 100 and 75% in the group with CEA elevation less than three-fold (10-14.9 ng/ml) and 95 and 62% in the group with elevation more than three-fold (≥ 15 ng/ml). The sensitivity and specificity of 18F-FDG PET/CT were computed as 98 and 85% in the lesion-based evaluation. The sensitivity and specificity of ceCT were 73 and 86%, respectively. 18F-FDG PET/CT is a safe imaging method that can be used in the determination of CRC recurrence in patients with elevated CEA levels, regardless of the CEA level.


Development of a mapping function ("crosswalk") for the conversion of scores between the Oswestry Disability Index (ODI) and the Core Outcome Measures Index (COMI).
The Oswestry Disability Index (ODI) and the Core Outcome Measures Index (COMI) are two commonly used self-rating outcome instruments in patients with lumbar spinal disorders. No formal crosswalk between them exists that would otherwise allow the scores of one to be interpreted in terms of the other. We aimed to create such a mapping function. We performed a secondary analysis of ODI and COMI data previously collected from 3324 patients (57 ± 17y; 60.3% female) at baseline and 1y after surgical or conservative treatment. Correlations between scores and Cohen's kappa for agreement (κ) regarding achievement of the minimal clinically important change (MCIC) score on each instrument (ODI, 12.8 points; COMI, 2.2 points) were calculated, and regression models were built. The latter were tested for accuracy in an independent set of registry data from 634 patients (60 ± 15y; 56.8% female). All pairs of measures were significantly positively correlated (baseline, 0.73; 1y follow-up (FU), 0.84; change-scores, 0.73). MCIC for COMI was achieved in 53.9% patients and for ODI, in 52.4%, with 78% agreement on an individual basis (κ = 0.56). Standard errors for the regression slopes and intercepts were low, indicating excellent prediction at the group level, but root mean square residuals (reflecting individual error) were relatively high. ODI was predicted as COMI × 7.13-4.20 (at baseline), COMI × 6.34 + 2.67 (at FU) and COMI × 5.18 + 1.92 (for change-score); COMI was predicted as ODI × 0.075 + 3.64 (baseline), ODI × 0.113 + 0.96 (FU), and ODI × 0.102 + 1.10 (change-score). ICCs were 0.63-0.87 for derived versus actual scores. Predictions at the group level were very good and met standards justifying the pooling of data. However, we caution against using individual values for treatment decisions, e.g. attempting to monitor patients over time, first with one instrument and then with the other, due to the lower statistical precision at the individual level. The ability to convert scores via the developed mapping function should open up more centres/registries for collaboration and facilitate the combining of data in meta-analyses.


Molecules derived from tRNA and snoRNA: Entering the degradome pool.
Molecules built of RNA have been the subjects of numerous studies, which have made known new functions and structures that these molecules can create. In recent years, thanks to next-generation sequencing, it is possible to observe very small RNAs and the number of newly discovered RNA molecules is rapidly increasing. Among other small oligonucleotides, structures derived from tRNA and snoRNA molecules have been observed, and these molecules were determined to not be precursors of known RNA molecules. These structures have attracted the attention of researchers because the level of accumulation of tRNA or snoRNA fragments was relatively high. Additionally, other parts of the parent molecules were absent. Derivatives of well-known RNA molecules also have functions that are different from their parent molecules. They are mainly involved in regulating the expression of genetic information in a similar way to miRNA. In addition, some of the miRNAs that have been described are derivatives of tRNA or snoRNA. Most of the research on these newly discovered molecules is based on their detection and on the study of the macro effects that they exert, in the absence of a description of the molecular mechanism by which they arise and work.


Measurement of brachial plexus strain in arthroscopy of the shoulder.
The purpose of this study was to measure the strain on the brachial plexus that results from traction loads applied at various arm positions and to correlate this with visibility through the arthroscope. We mounted strain gauges to the upper trunk, lateral cord, median nerve, and radial nerve of five fresh human cadavers. Each cadaver was placed in a lateral decubitus position, with the head fixed in a neutral position, as for shoulder arthroscopy, and the strain on the plexus was measured as a function of arm position and traction load. A final cadaver was used to determine the accessibility and visibility in the arthroscope at each of the arm positions. At a given flexion angle, increasing abduction is associated with decreasing strain. At a given abduction angle, increasing flexion results in decreased strain. The minimum overall strain was noted at 90 degrees of flexion and 0 degree of abduction. Visibility at this position is limited. We conclude that the ideal arthroscopic position is a combination of two positions that would maximize visibility while minimizing strain to the nerves. These two positions are 45 degrees of forward flexion and 90 degrees of abduction in combination with 45 degrees of forward flexion and 0 degree of abduction.


IgG4 antibodies in patients with atopic dermatitis.
The role of IgG4 in atopic dermatitis was investigated by determining the total amounts of IgG4 and of IgG4 specific for ovalbumin (a food allergen), Dermatophagoides farinae mite antigen and house dust (inhalant allergens) and Candida. These were related to the amounts of total and antigen specific IgE in patients with atopic dermatitis and normal healthy controls. Most patients with atopic dermatitis had greater amounts of total IgG4 and of antigen-specific IgG4 than did normal control individuals. Patients who had received hyposensitization treatment injections had greater amounts of IgG4 than the atopic dermatitis patients not so treated. In patients treated by hyposensitization there was a large increase in the amount of blocking antibody detected by incubating the antigen with the serum overnight before injecting the mixture into the skin of a patient sensitive to the antigen. Blocking activity was also examined by partial inhibition by the serum of IgE-mediated mast cell degranulation and by injection of serum into the skin of sensitive patients before challenge with antigens. In all tests the blocking activity of the serum was related to the amount of antigen-specific IgG4 but not related to total IgG4. In patients with atopic dermatitis who were sensitive to mite antigen, severe cases had small amounts of specific IgG4 and large amounts of specific IgE but in mild cases there was an opposite trend with relatively large amounts of specific IgG4. Large amounts of IgG4 ovalbumin specific antibody were found in children and adults with atopic dermatitis and egg allergy but small amounts of IgE. In infants most of the anti-ovalbumin antibody was IgE with little or no IgG4. The work of others has confirmed that increased amounts of total and antigen-specific IgG4 occur in atopic dermatitis, and it is concluded that IgG4 is a blocking antibody for anaphylactic sensitization responses.


Snakebites and ethnobotany in the northwest region of Colombia: Part I: traditional use of plants.
In Antioquia and Chocó, traditional healers attend 60% of snakebites. With the aim to produce an inventory of the plants used by the healers to treat snakebites and to document the methods of preparation, administration, the dosage, number of patients treated throughout their years of practice with treatment results, 20 healers with experience in Bothrops, Porthidium and Bothriechis envenomations were interviewed between August, 1996 and November, 1998. They belong to nine black and three indigenous rural communities located near the towns of Bojayá, Vigía del Fuerte, Unguía (Atrato river valley), Nuquí and Bahía Solano (Pacific coast). Based on field interviews, 101 species of plants were identified as used to treat snakebites. The part used of each plant varies according to the species. Sixty plants are used in the form of drinks prepared by infusion, decoction or maceration; 78 as external baths on the affected extremity; 11 for steam application and 39 for poultices; the latter is used mainly when the bite is complicated by local necrosis. In mild and moderate envenomations, they generally use a mixture of three plants, while in severe cases they mix from five to 12, a handful of each one. Treatment is generally performed for 1-3 days, when the patient reacts positively. They reported to have treated 454 patients during their years of experience, 20 of them (4.4%) died. With the guidance of the healers, 77 species of plants were collected and photographed. These plants belong to 41 families, of which Piperaceae (13 species), Araceae (six species), Asteraceae (five species) and Gesneriaceae (three species) have the highest number of species.


Characteristics of drowning deaths in an inner city river.
A study was undertaken of all drowning deaths that occurred over a 30-year period from 1988 to 2017 in the urban section of the River Torrens, Adelaide, South Australia, an augmented waterway that runs through the central business district. Autopsy records from Forensic Science South Australia (FSSA) were reviewed. There were 34 drownings (0-5 cases/yr) with 28 males and 6 females (M;F = 4.6:1), with an age range for males of 18-76yrs (mean 42.0; SD 18.0) and for females of 20-84yrs (mean 69.3; SD 24.5). There were 15 (44%) accidents, 11 (32%) suicides, 1 (3%) homicide and 7 (21%) undetermined. Of the 22 cases during or after 1994 with complete toxicology reports, 10 (45%) had a blood alcohol concentration (BAC) of greater than 0.05% (g/100 mL) with an illicit substance detected in 4 (18%) cases: (MDMA (3,4-methylenedioxymethamphetamine), methylamphetamine and THC (delta-9-tetrahydrocannabinol) acid). The presence of various therapeutic drugs was also detected in 10 cases (45%) including temazepam, fluoxetine, diazepam, olanzapine, amitriptyline, carbamazepine, codeine, citalopram and valproate. Although the numbers of cases were not high, the urban portion of the River Torrens had a much higher number of drowning events per kilometre compared to other inland waterways in South Australia such as the Murray River. This is most likely due to the vulnerability that exists for intoxicated individuals in the city from falls into the water and to the availability of the river as a means of suicide to members of the adjacent urban population.


The oral toxicity of 1-amino-3-chloro-propanol hydrochloride (CL 88236) in rats.
1-amino-3-chloro-2-propanol (CL 88236) was administered by oral gavage for 12 consecutive weeks to rats at dose levels of 50, 250 and 500 mg/kg/day. All levels gave rise to toxicological effects. Epididymal necrosis and/or atrophy of the seminiferous epithelium was found for some males with each dose of CL 88236. The kidney and liver weights of male and female rats given CL 88236 were higher than control values but no histological changes were found in these organs.


Function of alloproliferative T lymphocyte clones correlates better with their class II recognitive specificity than with their cell surface phenotype.
Alloproliferative primed lymphocyte typing (PLT) clones recognizing determinants associated with HLA-DR/Dw, SB, MB, or novel "SB-like" gene products were screened for their ability to suppress lymphoproliferative responses in primary and secondary mixed lymphocyte cultures (MLC), and for their surface marker phenotypes. Two nonsuppressive HLA-D specific PLT clones were OKT4-, OKT8+ whereas all others possessed an OKT4+, OKT8-, Leu-8- phenotype. All clones secreted interleukin 2 (IL2) after specific stimulation. The eight PLT clones specific for "SB-like" antigens strongly suppressed MLC, whereas only one of 35 DR/Dw-specific, and none of 20 SB-specific PLT clones did so. Suppressive activity of such PLT clones was not restricted by major histocompatibility complex products, was radioresistant (20 Gy), and was not caused by absorption of IL2 or by cytotoxicity of the cloned cells. Suppressive clones exerted their effects directly on proliferating T cells, as assessed by their ability to prevent growth of cloned PLT cells stimulated by B cell lines, and their ability to block primary MLC even when added 96 h after the start of the 144-h culture. Culture supernatants from suppressive, but not from nonsuppressive, PLT clones also strongly and nonspecifically inhibited lymphoproliferative responses. The suppressive factor(s) was not dialyzable, not sensitive to pH 2 or heat treatment and not cytotoxic. Thus, all T cell clones proliferating against novel "SB-like" but not SB antigens, as well as rare clones specific for D region determinants, possess powerful nonspecific suppressive activities dissociated from their "helper-related" OKT4+, OKT8-, Leu 8-, IL2-secreting phenotypes.


Structural and functional organization of the nuclear envelope.
The double-membrane nuclear envelope is punctuated by pores where the two membranes are joined. These pores are stabilized by the elaborate nuclear pore complex, which is anchored to the inner membrane by the nuclear lamina, as well as to other nuclear and cytoskeletal structures. Recent experiments have identified proteins involved in the stability of this organization as well as in the function of the nuclear pore complex, which we relate here to newer aspects of nuclear envelope structure.


Ultrasonic assisted extraction combined with titanium-plate based solid phase extraction for the analysis of PAHs in soil samples by HPLC-FLD.
In this work, ultrasonic assisted extraction combined with solid phase extraction (SPE) was applied in the analysis of polycyclic aromatic hydrocarbons (PAHs) in environment samples. A titania nanotubes/titanium plate was modified with n-octadecanethiol monolayer-protected Ag nanoparticles, and developed as the adsorbent in SPE of PAHs. Six different PAHs in soil samples were analyzed with high performance liquid chromatography-fluorescence detection. The experiment conditions including the deposition time of Ag nanoparticles, extraction solvent properties, the amount of extraction solvent, the amount of organic modifier, extraction time, and desorption solvent properties were optimized. Under the optimized conditions, good linearity and low limits of detection of 0.0015-0.4 ng g(-1) were obtained. The analysis of PAHs in real soil samples gave satisfactory recoveries ranging from 70.32% to 115.51% with 3.14%-13.56% intra-day relative standard deviations (RSD) and 4.92%-14.87% inter-day RSD.


Dialysis patient characteristics and outcomes: the complexity of social work practice with the end stage renal disease population.
This article describes a demonstration project designed to explore psychosocial risk and resiliency factors, social work interventions and health-related outcomes with dialysis patients. The study is unique in including an interdisciplinary research team to guide the process, using available data contained within the medical record and focusing on interventions and outcomes over time rather than at one or two points in patients' treatment histories. It demonstrates the complexity of practice with dialysis patients and the crucial role for social workers in enhancing patient outcomes. Secondary benefits of this methodology and implications for social work practice and research are discussed.


Application progress of ultrasonication in flour product processing: A review.
Flour products played a vital role in the global diet structure. With the increasing demand for dietary health and food standardization, the staple food of flour products made from coarse grains due to its unique flavor and rich nutrition has become a trend and is favored by consumers. However, the lack of gluten protein in the raw materials prevented the formation of a stable gluten network structure, leading to the deterioration of the quality of flour products. Ultrasonic treatment, as an innovative food processing technology, generated energy during the action of ultrasonic waves that had a positive impact on the texture, organizational structure, or flavor characteristics of food. That was of great significance for improving food production efficiency, improving food processing quality, and extending food shelf life. This article applied ultrasonic technology to the processing of flour products from the perspective of promoting fermentation and improving production efficiency of flour products. The cavitation effect of ultrasound promoted the formation of gluten network structure, improved the rheology properties of dough and the quality of flour products by promoting protein cross-linking, improving the foaming and emulsifying stability of gluten protein, and promoting the growth and reproduction of yeast. All reviewed studies indicate that ultrasound would be a promising technology for producing high-quality surface products under appropriate conditions.


Effect of graphene oxide on the uptake, translocation and toxicity of metal mixture to Lepidium sativum L. plants: Mitigation of metal phytotoxicity due to nanosorption.
Due to its unique structure and exceptional properties, graphene oxide (GO) is increasingly used in various fields of industry and therefore is inevitably released into the environment, where it interacts with different contaminants. However, the information relating to the ability of GO to affect the toxicity of contaminants is still limited. Therefore, the aim of our study was to synthesize GO, to examine the phytotoxicity of different concentrations of GO and its co-exposure with the metal mixture using garden cress (Lepidium sativum L.) as a test organism and to evaluate the potential of GO to affect toxicity of metals and their uptake by plants. The metal mixture (MIX) containing Ni (II), Zn (II), Cr (III) and Cu (II) was prepared in accordance with the maximum-permissible-concentrations (MPC) accepted for the inland waters in the EU. Additionally, the capacity of GO to adsorb metals was studied in specific conditions of the phytotoxicity test and assessed using adsorption isotherms. Our data indicate that in most cases the tested concentrations of MIX, GO and MIX + GO did not affect seed germination, root growth and biomass of roots and seedlings, however, they were found to alter photosynthesis processes, enhance production of carotenoids and H2O2 as well as to activate lipid peroxidation. Additionally, our study revealed that GO affects the accumulation of tested metals in roots and shoots of the MIX-exposed L. sativum. This is due to the capacity of GO to adsorb metals from the growth medium. Therefore, low concentrations of GO can be used for water decontamination.


Neurospecific proteins in the serum of patients with brain tumors.
Neurospecific proteins S-100 and GFAP were measured in the serum of 145 patients with neural tumors and 69 healthy individuals. In patients with glyoblastomas, the concentrations of S-100 and GFAP were significantly higher than in patients with anaplastic astrocytomas, benign meningiomas, and brain metastases and in healthy individuals. Serum S-100 concentrations in patients with anaplastic astrocytomas, benign meningiomas, and brain metastases were similar; significant difference from the control was found only for patients with cerebral metastases. A specific feature of GFAP was high incidence of its detection in patients with glioblastomas (83%) compared to other groups of patients with neural tumors and healthy volunteers who demonstrated practically zero level of this protein. These findings attest to the possibility of using S-100 as an additional biochemical criterion of brain involvement in tumor patients and GFAP as a glioblastoma marker.


Cardiac device infection: Review based in the experience of a single center.
The incidence of cardiac implantable electronic device infections has increased significantly over the years and they are associated with significant morbidity and mortality. The epidemiology in the Central region of Portugal is not known. To characterize cardiac implantable electronic device infections through a retrospective study of 3158 patients admitted to our center between January 2008 and September 2014 and to review the subject in the light of the current state of the art. The infection rate was 1.48% (pacemakers 1.21%, cardiac defibrillator/resynchronization devices 5.40%). The study population consisted of 47 patients with a mean age of 65±19 years, predominantly male (72.3%). Infections were mainly of pacemakers, the main device implanted in our population (n=2954), and most occurred late after first implantation. Clinically, most patients presented with fever and local inflammation. Blood cultures identified mainly Gram-positive microorganisms. Empiric antibiotic therapy with vancomycin was instituted in all patients, associated with gentamicin in 57%. The device was extracted in the majority of cases (72%). During follow-up (32±22 months) eight patients died (17%), seven of cardiovascular cause (15%), and seven were readmitted with device infection (15%). Our rate of infection was low, similar to other published series, with a higher rate in cardiac defibrillator/resynchronization devices. After standard treatment with antibiotic therapy and device extraction, the prognosis was good.


High-throughput imaging method for direct assessment of GM1 ganglioside levels in mammalian cells.
GM1-gangliosidosis is an inherited autosomal recessive disorder caused by mutations in the gene GLB1, which encodes acid β-galactosidase (β-gal). The lack of activity in this lysosomal enzyme leads to accumulation of GM1 gangliosides (GM1) in cells. We have developed a high-content-imaging method to assess GM1 levels in fibroblasts that can be used to evaluate substrate reduction in treated GLB1(-/-) cells [1]. This assay allows fluorescent quantification in a multi-well system which generates unbiased and statistically significant data. Fluorescently labeled Cholera Toxin B subunit (CTXB), which specifically binds to GM1 gangliosides, was used to detect in situ GM1 levels in a fixed monolayer of fibroblasts. This sensitive, rapid, and inexpensive method facilitates in vitro drug screening in a format that allows a high number of replicates using low working volumes.


The presbyopic add. II. Age-related trend and a gender difference.
New transverse clinical data are presented which confirm and extend earlier results to be found in the literature describing the time course of presbyopia-as indicated by the magnitude of the binocular spectacle add--in normally sighted male and and female Caucasian subjects. An initial steep increase in add requirement beginning in the early forties becomes relatively slower but still of significance beyond the mid-fifties. This observation is correlated with the age-related progressive decline in the amplitude of accommodation, itself a consequence of physiological changes in the crystalline lens and capsule. The continuing need for an increase, albeit at a reduced rate, in the positive near supplement beyond the mid-to-late fifties-by which time little or no useful accommodation is available-is now attributed to the visually disruptive effects within the high spatial frequency domain of progressive age-related lenticular changes. The magnification afforded by the positive add increases spatial grain and thereby enhances visibility of detail in an ageing visual system free of any gross senile visual pathology. A small but consistent gender difference is revealed in presbyopic corrections: physiological and physical bases are suggested for the observation that females require an add of greater magnitude than their age-matched male counterparts.


Linkage of Charcot-Marie-Tooth neuropathy type 1a to chromosome 17.
Charcot-Marie-Tooth disease Type 1 (CMT) is an inherited neuropathy with known genetic heterogeneity, with at least one autosomal dominant form (CMT Type 1b) linked to the Duffy region of chromosome 1. Autosomal dominant families not demonstrating linkage to the Duffy blood group marker have been designated CMT Type 1a. We report linkage of six CMT Type 1a families to the chromosome 17 markers EW301 (D17S58) and pA10-41 (D17S71) with maximum LOD scores of zeta = 10.49 at theta (maximum recombination fraction) = 0.05 and zeta = 7.36 at theta = 0.06, respectively.


Degradation behavior of 2D auxetic structure with biodegradable polymer under mechanical stress.
Coronary heart disease is serious harm to human health. Vascular scaffold implantation is the main treatment. Biodegradable polymers are widely used in vascular scaffolds for good biodegradability and biocompatibility. However, whether the mechanical properties and radial expansion ability can successfully implant the scaffold without acute elastic retraction remains to be further studied. Because of the unique deformation mechanism, shear resistance, and resilience, auxetic structures can effectively avoid the restenosis of degraded vascular scaffolds. Firstly, the plane isotropic and plane anisotropic auxetic structural scaffolds were designed. The control structures (traditional structures) scaffolds were taken as the contrast. PCL was used to prepare the vascular auxetic by 3D printing. The printing parameters of fused deposition 3D printing, such as printing temperature, printing speed, and printing pressure, were studied to determine the optimal printing parameters of PCL. A self-assembled cyclic tensile stress loading device was used to investigate the degradation behavior of different scaffolds under different sizes of cyclic tensile stress, such as surface morphology, pH changes, mass loss rate, and mechanical properties. The increase of stress, surface roughness, and mass loss rate of the scaffolds all showed an increasing trend. pH gradually decreased from the fifth week, and the decrease was proportional to the stress. A large level of stress loading intensifies the decline of elastic modulus and the ultimate strength of the scaffold. In conclusion, the increase of periodic tensile stress will accelerate the degradation of scaffolds, and the degradation behavior of scaffolds with different configurations is different. The degradation rate of dilatant scaffolds was higher than that of control scaffolds, and the degradation rate of anisotropic auxetic scaffolds was higher than that of isotropic auxetic scaffolds, which provides a theoretical reference for the application of auxetic structure in the degradation of vascular scaffolds.


The ability of older people to overcome adversity: a review of the resilience concept.
Resilience has been recognized as the ability to bounce back from adversity and regain health. This review seeks to explore the validity of the current understanding of resilience as it applies to older people and its application as guide for interventions. One mixed method, 19 qualitative and 22 quantitative papers were located through a systematic search of nine databases. Results confirmed a number of themes of personal resources. Older people who have the ability to use personal resources and see the world beyond their own concerns are more likely to be resilient. In addition a number of environmental factors were identified including social support from community, family and professionals as well as access to care, availability of resources and the influence of social policy and societal responses. Nurses can facilitate resilience of older people by maintaining or enhancing social support and facilitating access to care and resources.


Association of Epidural Analgesia in Women in Labor With Neonatal and Childhood Outcomes in a Population Cohort.
Although use of epidural analgesia during labor is safe, detailed information about its association with neonatal and child outcomes is limited. To investigate the association of labor epidural analgesia with neonatal outcomes and childhood development during the first 1000 days of life. This population-based cohort study used Scottish National Health Service hospital administrative data of all 435 281 singleton live births in Scotland between January 1, 2007, and December 31, 2016, with follow-up over the first 1000 days of life. All 435 281 mother-infant pairs delivering between 24 weeks 0 days and 43 weeks 6 days' gestation who were in active labor with cephalic presentation and who delivered vaginally or via unplanned cesarean delivery were included. Stillbirths and infants with known congenital anomalies were excluded. Data were analyzed between August 1, 2020, and July 23, 2021. Epidural analgesia in labor. Neonatal outcomes included resuscitation, Apgar score less than 7 at 5 minutes, and neonatal unit admission. Childhood development measures (gross and fine motor function, communication, and social functioning) were obtained from standardized national childhood surveillance assessments performed at 2 years. This study included a total of 435 281 live births with cephalic presentation in labor (median gestational age at delivery, 40 weeks [IQR, 39-41 weeks]; 221 153 male infants [50.8%]), of which 94 323 (21.7%) had labor epidural. Epidural analgesia was associated with a reduction in spontaneous vaginal deliveries (confounder-adjusted [Cadj] relative risk [RR], 0.46; 95% CI, 0.42-0.50), an increased risk of neonatal resuscitation (Cadj RR, 1.07; 95% CI, 1.03-1.11), and an increased risk of neonatal unit admission (Cadj RR, 1.14; 95% CI, 1.11-1.17). With additional analysis for mediation by mode of delivery (CMadj), these associations were reversed (CMadj RR, 0.83; 95% CI, 0.79-0.86 for neonatal resuscitation and CMadj RR, 0.94; 95% CI, 0.91-0.97 for neonatal unit admission). Epidural analgesia was associated with a reduced risk of an Apgar score less than 7 at 5 minutes in both confounder and confounder/mediation analyses. Epidural analgesia was associated with a reduced risk of having developmental concern in any domain at 2 years in confounder and confounder/mediation analyses (CMadj RR, 0.96; 95% CI, 0.93-0.98), with specifically fewer concerns regarding communication (CMadj RR, 0.96; 95% CI, 0.93-0.99) and fine motor skills (CMadj RR, 0.89; 95% CI, 0.82-0.97). The results of this cohort study suggest that labor epidural analgesia is not independently associated with adverse neonatal or childhood development outcomes. Associations with neonatal resuscitation and admission were likely mediated by mode of delivery.


Botulinum Toxin Type A Injection for Mammoplasty and Abdominoplasty Scar Management: A Split-Scar Double-Blinded Randomized Controlled Study.
Scars are inevitable results of surgical procedures, and prevention of them is still a major problem in the field of cosmetic surgery. Although various studies have been performed on botulinum toxin-A (BoNT-A) injection for the prevention of hypertrophic scars, the exact mechanism remains unclear. This prospective, double-blinded, randomized study was performed on 19 patients who underwent mammoplasty and abdominoplasty surgery in Razi Hospital from October 2018 to December 2019. Single session of treatment was performed, where XEOMIN was allocated to one half of the scar and 0.9% saline to the control half. 3 and 6 months later, scars were assessed using the modified Stony Brook Scar Evaluation Scale (SBSES). In total, 19 patients who completed the study were analyzed. mSBSES at the third month (P value < 0.001; 3.34 ± 1.59 vs 1.5 ± 1.36) and the sixth month (P value < 0.001; 4.89 ± 1.83 vs 2.39 ± 1.82) showed a significant difference between the treatment and control groups. In the subset analysis, there was significant difference between BoNT-A and control in all four items including width, height, color, and scar visibility at months 3 and 6, and the BoNT-A-treated sides had higher scores in all items. BoNT-A has a significant effect on scar prevention due to mammoplasty and abdominoplasty compared to placebo and results in decreased erythema, height, width and reduces incision line visibility. Moreover, its effect increases significantly over time from months 3 to 6. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Cancer-specific calcium nanoregulator suppressing the generation and circulation of circulating tumor cell clusters for enhanced anti-metastasis combinational chemotherapy.
Tumor metastasis is responsible for chemotherapeutic failure and cancer-related death. Moreover, circulating tumor cell (CTC) clusters play a pivotal role in tumor metastasis. Herein, we develop cancer-specific calcium nanoregulators to suppress the generation and circulation of CTC clusters by cancer membrane-coated digoxin (DIG) and doxorubicin (DOX) co-encapsulated PLGA nanoparticles (CPDDs). CPDDs could precisely target the homologous primary tumor cells and CTC clusters in blood and lymphatic circulation. Intriguingly, CPDDs induce the accumulation of intracellular Ca2+ by inhibiting Na+/K+-ATPase, which help restrain cell-cell junctions to disaggregate CTC clusters. Meanwhile, CPDDs suppress the epithelial-mesenchymal transition (EMT) process, resulting in inhibiting tumor cells escape from the primary site. Moreover, the combination of DOX and DIG at a mass ratio of 5:1 synergistically induces the apoptosis of tumor cells. In vitro and in vivo results demonstrate that CPDDs not only effectively inhibit the generation and circulation of CTC clusters, but also precisely target and eliminate primary tumors. Our findings present a novel approach for anti-metastasis combinational chemotherapy.


Association of Epsilon-Aminocaproic Acid With Blood Loss and Risk of Transfusion After Periacetabular Osteotomy: A Retrospective Cohort Study.
Periacetabular osteotomy (PAO) reorients the acetabular cartilage through a complex series of pelvic osteotomies, which risks significant blood loss often necessitating blood transfusion. Therefore, it is important to identify effective strategies to manage blood loss and decrease morbidity after PAO. The purpose of this study was to determine the association of epsilon-aminocaproic acid (EACA), an antifibrinolytic agent, with blood loss from PAO. Ninety-three patients out of 110 consecutive patients that underwent unilateral PAO for acetabular dysplasia met inclusion criteria. Fifty patients received EACA intraoperatively. Demographics, autologous blood predonation, anesthetic type, intraoperative estimated blood loss (EBL), cell-saver utilization, and transfusions were recorded. Total blood loss was calculated. Two-sample t-test and chi-square or Fisher's exact test were used as appropriate. The associations between EACA administration and calculated EBL, cell-saver utilization, intraoperative EBL, and maximum difference in postoperative hemoglobin were assessed via multiple regression, adjusting for confounders. Post hoc power analysis demonstrated sufficient power to detect a 250-mL difference in calculated EBL between groups. Alpha level was 0.05 for all tests. No demographic differences existed between groups. Mean blood loss and allogeneic transfusion rates were not statistically significant between groups (P = .093 and .170, respectively). There were no differences in cell-saver utilization, intraoperative EBL, and/or postoperative hemoglobin. There was a higher rate of autologous blood utilization in the group not receiving EACA because of a clinical practice change. EACA administration was not associated with a statistically significant reduction in blood loss or allogeneic transfusion in patients undergoing PAO.


Students' knowledge of and attitudes towards primary health care.
The aims of this study were to assess nursing students' knowledge of and attitudes towards primary health care using a newly developed Canadian instrument, the Primary Health Care Questionnaire (PHCQ). The instrument was refined for use in the UK prior to collecting data from 427 students in degree, Project 2000, health visitor and district nursing courses. Findings indicate that students in all programmes surveyed have been exposed to the concepts of primary health care. Students have acquired knowledge about primary health care and, generally, positive attitudes to the concepts. Significant differences were found between several student groups on both the knowledge and attitude measures. Although further psychometric evaluation of this new measure is recommended, the PHCQ shows promise as a valuable measure for use in assessing the move toward an increased emphasis on primary health care concepts in nursing education.


Retrograde tracing and toe spreading after experimental autologous nerve transplantation and crush injury of the sciatic nerve: a descriptive methodological study.
Evaluation of functional and structural recovery after peripheral nerve injury is crucial to determine the therapeutic effect of a nerve repair strategy. In the present study, we examined the relationship between the structural evaluation of regeneration by means of retrograde tracing and the functional analysis of toe spreading. Two standardized rat sciatic nerve injury models were used to address this relationship. As such, animals received either a 2 cm sciatic nerve defect (neurotmesis) followed by autologous nerve transplantation (ANT animals) or a crush injury with spontaneous recovery (axonotmesis; CI animals). Functional recovery of toe spreading was observed over an observation period of 84 days. In contrast to CI animals, ANT animals did not reach pre-surgical levels of toe spreading. After the observation period, the lipophilic dye DiI was applied to label sensory and motor neurons in dorsal root ganglia (DRG; sensory neurons) and spinal cord (motor neurons), respectively. No statistical difference in motor or sensory neuron counts could be detected between ANT and CI animals.In the present study we could indicate that there was no direct relationship between functional recovery (toe spreading) measured by SSI and the number of labelled (motor and sensory) neurons evaluated by retrograde tracing. The present findings demonstrate that a multimodal approach with a variety of independent evaluation tools is essential to understand and estimate the therapeutic benefit of a nerve repair strategy.


Volatiles of two chemotypes of Majorana syriaca L. (Labiatae) as olfactory cues for the honeybee.
A study of olfactory discrimination by honeybee has been set up in order to understand the role of volatiles of the aromatic plant Majorana syriaca in attracting pollinating insects. The honeybee's response to volatiles from leaves and inflorescences of two M. syriaca chemotypes, which differ in the thymol carvacrol ratio of their volatiles, was tested using a bioessay method based on associative conditioning and recruitement techniques. Behavioural data show that a honeybee identifies and reacts selectively to olfactory signals from leaves and from inflorescences of the two chemotypes. Such data suggest that the volatiles from all parts of the aromatic plant M. syriaca may have a role in attracting pollinators. The vegetative parts produce a volatile emission which attracts the pollinators from a distance towards the whole plant. At close range these are directed by the flower signal which is amplified by the volatiles of bracts and leaves in the inflorescence.


Double Heterozygous Mutations (Cys247Tyr and 252delAsn) Cause Factor XII Deficiency in a Chinese Family.
To study the molecular basis of human coagulation factor XII (FXII) deficiency in a Chinese family. Routine blood coagulation indexes were detected by a one-stage clotting method, whereas FXII antigen was detected by enzyme linked immunosorbent assay. DNA sequencing was applied to find mutations in the F12 gene. Bioinformatics and conservative analyses were performed to analyze possible effects of the mutation. The proband had significantly prolonged activated partial thromboplastin time (141.9 seconds), and her FXII clotting activity was decreased to 5%. Genetic analysis revealed that the propositus carried a heterozygous missense mutation c.797G > A in exon 8 resulting in Cys247Tyr and deletion mutation c.809_811delACA in exon 9 resulting in 252delAsn. Bioinformatics results indicated that the mutation had affected the function of the protein. The c.797G > A heterozygous missense variation and the c.809_811delACA heterozygous deletion variation are associated with decreased FXII levels in this family, of which c.797G > A is first reported in the world.


The brown adipocyte protein CIDEA promotes lipid droplet fusion via a phosphatidic acid-binding amphipathic helix.
Maintenance of energy homeostasis depends on the highly regulated storage and release of triacylglycerol primarily in adipose tissue, and excessive storage is a feature of common metabolic disorders. CIDEA is a lipid droplet (LD)-protein enriched in brown adipocytes promoting the enlargement of LDs, which are dynamic, ubiquitous organelles specialized for storing neutral lipids. We demonstrate an essential role in this process for an amphipathic helix in CIDEA, which facilitates embedding in the LD phospholipid monolayer and binds phosphatidic acid (PA). LD pairs are docked by CIDEA trans-complexes through contributions of the N-terminal domain and a C-terminal dimerization region. These complexes, enriched at the LD-LD contact site, interact with the cone-shaped phospholipid PA and likely increase phospholipid barrier permeability, promoting LD fusion by transference of lipids. This physiological process is essential in adipocyte differentiation as well as serving to facilitate the tight coupling of lipolysis and lipogenesis in activated brown fat.


Atomic-scale visualization of chiral charge density wave superlattices and their reversible switching.
Chirality is essential for various phenomena in life and matter. However, chirality and its switching in electronic superlattices, such as charge density wave (CDW) superlattices, remain elusive. In this study, we characterize the chirality switching with atom-resolution imaging in a single-layer NbSe2 CDW superlattice by the technique of scanning tunneling microscopy. The atomic arrangement of the CDW superlattice is found continuous and intact although its chirality is switched. Several intermediate states are tracked by time-resolved imaging, revealing the fast and dynamic chirality transition. Importantly, the switching is reversibly realized with an external electric field. Our findings unveil the delicate switching process of chiral CDW superlattice in a two-dimensional (2D) crystal down to the atomic scale.


Two novel oleanolic acid saponins having a sialyl Lewis X mimetic structure from Achyranthes fauriei root.
Two novel triterpene glycosides, achyranthosides E and F, were isolated as methyl esters from the root of Achyranthes fauriei, an antiinflammatory medicinal plant. Their structures were characterized as oleanolic acid glucuronides having unique substituents composed of C6H9O5 and C9H15O7, respectively, at the C-3 position of glucuronic acid. These compounds are active components which can inhibit the excess recruiting of neutrophiles to injured tissues 1,000 times more potently than sialyl Lewis X.


The recovery cycle of the pattern visual evoked potential in normal subjects and patients with multiple sclerosis.
The recovery cycle of amplitude and latency of the P100 of the chequerboard pattern reversal visual evoked response was studied in 16 normal subjects and 20 patients with multiple sclerosis. There was no clear-cut pattern of recovery with respect to amplitude but at interstimulus intervals of less than 40 msec the latency of the test response P100 tended to be significantly delayed, the magnitude of this delay being virtually constant at intervals of 20 msec or less. Only 8 of 40 eyes from the 20 multiple sclerosis patients showed a pattern of recovery of latency significantly different from the normal subjects. Possible mechanisms for these observations are discussed with particular reference to current concepts of the pathophysiology of multiple sclerosis.


A systematic review of patient surveillance after curative gastrectomy for gastric cancer: a brief review.
Complete resection of a gastric cancer and adjacent lymph nodes offers the only chance for cure of the disease. However, disease recurrence occurs in 22-51% of cases, and its prognosis is very poor. Many clinicians perform post-operative follow-up for these patients, although there is no consensus on the regimen, frequency of visits, mode of testing, or the rationale of a follow-up program. The objective of this systematic review was to identify the evidence for surveillance in patients with resected gastric cancer, specifically examining the interval of follow-up and the modalities utilized. Electronic literature searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from January 1st 1998 to December 1st 2009. All search titles and abstracts were independently rated for relevance by a minimum of two reviewers. Five articles were selected. A total of 810 patients underwent post-operative follow-up. History and physical examination, hematological and chemistry profile, endoscopy (esophagogastroduodenoscopy [EGD]), and computed tomography (CT) were the most frequently employed modalities. CT detected the majority of recurrences in the included studies. The survival post-recurrence was significantly higher in the asymptomatic group compared with symptomatic group in three studies, but this may simply reflect lead-time bias. No differences in overall survival (OS) were found. The included studies failed to show an improvement in OS with more intense surveillance. Further prospective studies are required to determine whether a subgroup of patients may benefit from more intensive follow-up.


The ontogenic appearance of tyrosine hydroxylase-, serotonin-, gamma-aminobutyric acid-, calcitonin gene-related peptide-, substance P-, and synaptophysin-immunoreactivity in rat pituitary gland.
The initial appearance of tyrosine hydroxylase (TH)-, serotonin (5-HT)-, gamma-aminobutyric acid (GABA)-, calcitonin gene-related peptide- (CGRP), substance P-, and synaptophysin-immunoreactivity in the rat pituitary gland, and in the related brain regions was investigated. Several groups of TH-immunoreactive neurons were first detected in the brain stem on day E17, and in the hypothalamus on day E18, followed by TH-immunoreactivity in the median eminence and infundibulum on E19-E20. TH-positive fibers appeared in the posterior lobe on day E20 and in the intermediate lobe on day P0. 5-HT-immunoreactivity was first detected on day E17 in neurons and nerve fibers in the brain stem and in the median eminence, respectively. On day E18, a few 5-HT-immunoreactive fibers were detected in the posterior lobe of the pituitary, although they were consistently seen in the infundibulum from day E19. In newborn rats, some 5-HT-immunoreactive fibers, but no neurons, were seen in the hypothalamus. GABA immunoreactivity appeared on day E17 in several nerve fibers of the infundibulum and the posterior lobe. Some neurons in the cortex and ventral hypothalamus transiently expressed GABA-immunoreactivity on day E17. In newborn rats, a plexus of GABA-immunoreactive fibers was detected for the first time in the intermediate lobe. No CGRP-immunoreactive fibers could be detected in the prenatal pituitary. On day P10, CGRP-immunoreactive fibers were first observed in the anterior lobe. Later their number considerably increased, while only sporadic fibers could be found in the intermediate or posterior lobes. No substance P-immunoreactivity could be detected in any of the lobes in the embryonic or developing postnatal rat pituitary, instead the adult anterior lobe occasionally showed some substance P-immunoreactive fibers. Synaptophysin-immunoreactivity was first detected in the posterior lobe on day E20, followed shortly by its expression in the intermediate lobe in newborn rats. The time course of GABA and 5-HT expression revealed in the present study suggests that these transmitters, which are initially expressed in the developing pituitary clearly before synaptic maturation, may act as trophic molecules during the prenatal period.


Manual therapy in the management of a patient with a symptomatic Morton's Neuroma: A case report.
Patients with Morton's neuroma are rarely referred to physical therapy. This case reports the resolution of pain, increase in local pressure pain thresholds, and improvement of scores on the Lower Extremity Functional Scale and Foot and Ankle Ability Measure following a course of joint based manual therapy for a patient who had failed standard conservative medical treatment.


A practical guide to determine the incision line in the treatment of septate uterus: "Süha-Levent's Sign".
To evaluate the significance of a new sign in the hysteroscopic incision process of the septate uterus. This is a prospective case control study. II-2. The study was performed in a research hospital. Fourty-seven consecutive cases were operated for septate uterus. Septum incision was performed in all cases with a hysteroscopic resectoscope under laparoscopic supervision. Methylene blue 0.25% was injected through a Rubin canula in all cases for the assessment of tubal patency. Following the methylene blue injection, hysteroscopic septum incision was performed. A line (blue line) on the top of the cavity has been observed in 33 of 47 (70.2%) cases. This line (blue line) can be used for determining the midline especially before hysteroscopic incision of uterine septum and can also shorten the operation time.


Three near-infrared and lysosome-targeting probes for photodynamic therapy (PDT).
Lysosome, an organelle which contains a number of hydrolases and hydrogen ions, plays a crucial role in cellular survival and apoptosis. If selectively destroy lysosomes membrane, inner hydrolases and hydrogen ions will leak and induce cell death. In this work, three lysosome-targeting fluorescent probes (HCL 1-3, heptamethine cyanine lysosomal-targeting probe) were designed, synthesized and developed for photodynamic therapy. Piperazine and N, N-dimethyl structures made HCL 1-3 have good lysosome targeting ability while Pearson's correlation coefficients reached 0.85, 0.87 and 0.78. It can be concluded from MTT test, HCL 1-3 have high photo cytotoxicity and low dark cytotoxicity from MTT test. Calcein/PI staining assays also supported cytotoxicity of HCL 1-3 under light conditions. In vivo experiments, HCL 2 accumulated in tumor and a strong fluorescence signal was observed at 12 h post injection. All results showed that our experiments provide help and new ideas for cyanine dyes in cancer treatment.


The measurement of Ca2+ effluxes from bone.
To facilitate the study of membrane function in the control of the flow of ions into and out of bone, it was desirable to develop a system for the direct quantitation of unidirectional effluxes of calcium and phosphate from bones. Based on a mathematical analysis of the problem, a specially designed Ussing chamber was developed which proved successful. Calvaria from 2-day-old rat pups, 3-day chicks and adult mice were evaluated. Calcium influxes which exceeded the corresponding effluxes were observed in the neonatal calvaria but not with those from adult mice. Also, an asymmetry in efflux was observed in rat calvaria, the inner side of the skull showed a higher efflux than did the external side. No such asymmetry was seen with calvaria from chicks or mice. This new technology should permit a further exploration of the role of the bone membrane in electrolyte homeostasis.


[Specific features of the protein fraction composition of seeds in plants of the subfamily Scilloideae].
The composition of protein complexes in seeds was studied in plants of the subfamily Scilloideae. Seed protein contents were compared in 59 species of 12 genera: Scilla L., Hyacinthus L., Bellevalia Lapeyr., Chionodoxa Boiss, Puschkinia Adam., Muscari Mill., Ornithogalum L., Eucomis L'Herit, Galtonia Desne, Velthemia Gleditsch., Hyacinthoides Linn., and Hyacinthella Schur. The results confirmed the heterogeneity of the subfamily: its constituent genera proved to differ in the composition of protein complexes and in the coefficient of evolutionary advancement. The group of salt-soluble proteins dominated by albumins prevailed in seeds of all species studied.


In situ synthesis of fluorescent membrane lipids (ceramides) using click chemistry.
Ceramide analogues containing azide groups either in the polar head or in the hydrocarbon chains are non-fluorescent. When incorporated into phospholipid bilayers, they can react in situ with a non-fluorescent 1,8-naphthalimide using click chemistry giving rise to fluorescent ceramide derivatives emitting at ≈440 nm. When incorporated into giant unilamellar vesicles, two-photon excitation at 760 nm allows visualization of the ceramide-containing bilayers. This kind of method may be of general applicability in the study of model and cell membranes.


Metabolic characterization of Kloeckera apiculata strains from star fruit fermentation.
A total of 37 strains of Kloeckera apiculata was isolated during the spontaneous fermentation of star fruit must. Each strain was differentiated from the others on the basis of its capacity to produce acetaldehyde, ethyl acetate, higher alcohols, acetoin and acetic acid. All the strains were characterized by the low production of higher alcohols and the high production of ethyl acetate, whereas consistent differences in the production of acetaldehyde, acetoin and acetic acid served to differentiate star fruit apiculate strains into six different phenotypes, present at different stages of the fermentation process. The metabolic strain diversity found can be interpreted as a natural consequence of environmental conditions, which influenced the frequency and selection of specific apiculate strains. From the biotechnological point of view the different metabolic biotypes represent an important source of strains for potential use as starter cultures for star fruit fermentation.


The cDNA of UL15, a highly conserved herpes simplex virus 1 gene, effectively replaces the two exons of the wild-type virus.
The UL15 gene of herpes simplex virus 1 (HSV-1) is encoded by two or more exons in all herpesvirus genomes sequenced to date. The UL15 coding region is highly conserved, and the intron invariably encodes other genes transcribed antisense to the UL15 coding region. Previously we reported that we deleted the intron domain encoding UL16 but were unable to delete UL15 (J. D. Baines and B. Roizman, J. Virol. 65:938-944, 1991). Here we report that we replaced exon I of UL15 with an unspliced cDNA copy of UL15 in HSV-1 DNA and deleted 58% of the carboxyl-terminal sequences of the natural copy of exon II, including the polyadenylation signal. The yields of infectious virus obtained upon infection with viruses containing the cDNA copy of UL15 were similar to those of an isogenic virus with a wild-type UL15 gene. We therefore conclude that the separation of the two exons of UL15 by an intron encoding two genes is not essential for the replication of HSV, at least in cell culture.


Luminescence behavior of Eu3+ doped LaF3 nanoparticles.
Europium-doped LaF3 nanoparticles have been prepared by the ionic reaction in the ethanol at 60 degrees C. From the XRD pattern of nanoparticles and the emission spectra of Eu3+ ions, it has been concluded that the Eu3+ ions could easily substitute the La3+ sites and the solid solution La(1-x)Eu(x)F3 can be synthesized. Due to very low phonon energies of LaF3 matrix, the 5D1 emission of Eu3+ ions in La(1-x)Eu(x)F3 nanoparticles can be observed at room temperature when doping concentration of Eu3+ ions is lower than 30 mol%. The quenching process of 5D1 emission can be attributed to cross-relaxation. Since clusters of Eu3+ ions and resonance energy transfer only occurs within one particle due to the hindrance by the particle boundary, the concentration quenching resulted from resonance energy transfer between neighboring Eu3+ ions occurs at higher Eu3+ concentrations in the Eu3+ doped LaF3 nanoparticles.


Studies on pharmacological activation of human immunoglobulin G by chemical modification and active subfragments. X. Effect of carboxamidemethylated Fc fragment (CM-Fc) from human immunoglobulin G on delayed type hypersensitivity.
The anti-allergic activity of the carboxyamidemethylated Fc fragment (CM-Fc) from human serum immunoglobulin G (IgG) was studied using sheep red blood cell-induced delayed type hypersensitivity in mice (SRBC-DTH). CM-Fc suppressed the DTH response when administered 30 min before, or 4 h after the SRBC challenge, but not when administered 8 h or more after the challenge. The Fc fragment showed no activity. CM-Fc administration 30 min before the challenge was unable to suppress the DTH response in the cyclophosphamide (CY)-treated mice. However, adoptive transfer of splenocytes from mice treated with CM-Fc to CY-pretreated mice caused suppression of the SRBC-DTH response. These results suggest that CM-Fc suppressed the DTH response by mediating the function of CY-susceptible cells.


Network Meta-Analysis of Different Intravenous Glucocorticoid Regimes for the Treatment of Graves' Orbitopathy.
Background: Intravenous glucocorticoid (GC) has been proposed to treat moderately severe Graves' orbitopathy (GO); however, the optimal regime remains debatable. We therefore performed this network meta-analysis to objectively determine the comparative efficacy and safety of different intravenous GC regimes, including daily, weekly, or monthly intravenous regimes, for the treatment of GO. Methods: We electronically searched Medline (via PubMed), EMBASE (via OVID), and the Cochrane Central Register of Controlled Trials (CENTRAL) (via OVID) to retrieve randomized controlled trials (RCTs) investigating the comparative efficacy and safety of different intravenous GC regimes in GO patients from the inception of each database to March 2021. The latest search was updated in June 2021. The risk of bias of original studies was assessed using the Cochrane risk bias assessment tool. A random-effects Bayesian network meta-analysis was conducted using the Markov chain Monte Carlo (MCMC) simulation. Ranking probabilities of all regimes were calculated to rank all regimes. Statistical analysis was conducted using the ADDIS software. Results: A total of 10 studies involving 593 patients met the selection criteria. Network meta-analysis suggested that the weekly intravenous GC regime (WR) [response: odds ratio (OR), 4.27; 95% creditable interval (CrI); 1.82 to 11.02; clinical activity score change (CASC): standard mean difference (SMD), -0.59; 95% CrI; -1.19 to -0.03) and monthly intravenous regime (MR) (response: OR, 6.32; 95% CrI; 1.25 to 34.96; CASC: SMD, -1.17; 95% CrI; -2.32 to -0.01) were superior to the oral GC (OGC) regime in response and CASC. Meanwhile, pooled results also indicated that the WR was related to the decreased risk of AEs compared with the OGC regime (OR, 0.22; 95% CrI; 0.08-0.62) and daily intravenous GC regime (DR) (OR, 0.19; 95% CrI; 0.03-0.97). Ranking probabilities indicated that the MR and WR have a relatively higher probability of becoming the best option for response, proptosis, and AEs. Conclusion: Based on limited evidence, the WR or MR should be preferentially prescribed to treat patients with moderately severe GO. However, more studies with a large sample size should be conducted to further confirm our findings and compare the WR with the MR.


Adolescent deliveries in rural Cameroon: an 8-year trend, prevalence and adverse maternofoetal outcomes.
Adolescent deliveries remain a global public health concern especially in low- and middle-income countries where 95% of these deliveries occur. In Cameroon, adolescent pregnancies have a high disease burden due to their association with adverse pregnancy outcomes. We sought to evaluate the prevalence, trend and adverse maternofoetal outcomes of adolescent deliveries in a rural community in Cameroon. We carried out a retrospective register analysis of 1803 singleton deliveries in two health facilities located in the Oku sub-division over an 8-year period (2009 to 2016). We excluded: records without maternal age, babies born before arrival, birthweights less than 1000 g, multiple deliveries and deliveries before 28 weeks gestation. Data analysis was done using Epi info 18.104.22.168. The Fisher's exact test was used to compare categorical variables, while the chi-square test for trends was used to determine time trends. P-values below 5% were considered statistically significant. The 8-year prevalence of adolescent deliveries was 20.4% (95% CI = 18.6-22.4) with a significant, downward trend between 2009 and 2016 (P trend = 0.05). Second-fourth degree perineal tears were more likely to complicate adolescent (Age < 20 years) deliveries compared with their adult (Age ≥ 20 years) counterparts (OR = 2.9; 95% CI = 1.8-4.7; p < 0.001). Also, babies born to adolescent mothers were more likely to have a low birthweight (OR = 1.7; 95% CI = 1.1-2.6; p = 0.009) and be asphyxiated at the fifth minute of life (OR = 3.2; 95% CI = 1.9-5.5; p < 0.001). Over an eight-year period, the downward trend in the prevalence of adolescent deliveries was associated with a significant decrease in the trend of neonatal asphyxia at the fifth minute. Married adolescents and their babies were as likely to develop the complications of adolescent delivery such as second-fourth degree perineal tears (OR = 0.8; 95% CI = 0.4-1.6; p = 0.456), low birthweight (OR = 2.1; 95% CI = 0.9-4.7; p = 0.070) and fifth minute neonatal asphyxia (OR = 0.9; 95% CI = 0.4-2.0; p = 0.832) as single adolescents and their babies. The prevalence of adolescent deliveries in this rural community is high with one of every five babies born to an adolescent mother. Despite the downward trend indicating a decrease in adolescent deliveries, our study demonstrates the need to reinforce and effectively apply existing government-based public health programme to target key indicators of adolescent pregnancy in Cameroon.


Voice disorders in children.
The pediatric otolaryngologist has an especially important role in the differential diagnosis and treatment of two voice disorders; these are the voice quality problems (dysphony) and the resonance problems (rhinophony). The first step in the examination is to preclude the organic causes. The functional dysphonia is mostly related to voice abuse/misuse, but may be present on a psychosomatic basis; environmental factors can also play a role in the etiology and the personality structure has been found to be very relevant. The perceptual evaluation of voice is of obvious importance. Endoscopy with a transnasal flexible scope makes it possible, in practically all cases, to identify the morphodynamic changes. Stroboscopy and phonetography can be carried out only in older children, sometimes a 'trial treatment' is of valuable help. The therapy can be divided into five groups (counselling, voice re-education, drug treatment, psychotherapy, surgery), but should be always individual. An open question: how to choose the preferable treatment of vocal nodules: surgery, conservative or wait-and-see? According to a detailed survey in Kurume University Hospital the following can be stated: if the patient is in trouble due to hoarseness, and immediate improvement of his voice is necessary, surgery should be indicated; if they need the improvement but do not need it urgently, voice therapy is recommended; without motivation vocal hygiene is proposed. No matter what treatment patients receive, their voices improve in the majority after puberty, but 15% of the patients do not show any improvement. In cases of hoarseness due to long-term postintubational glottic lesions logopedic treatment is the only therapeutic possibility. The delay of speech development of tracheotomized children can and should be avoided by applying proper cannula technique and by logopedic training. The physiological nasality which depends upon the undisturbed activity of the velopharyngeal closure, can become pathologic in four forms: closed, open, mixed and alternating nasality (rhinophonolalia). In the diagnosis of hyperrhinophony due to VPI X-ray procedures, supplemented with nasendoscopy, proved to be the most informative methods, the etiology (neuromyogen processes) may be revealed by electrophysiological methods; the voice and speech can be assessed and visualized by nasometry, but the detailed speech evaluation is indispensable. The basic possibilities of treatment are as follows: speech therapy, surgery, speech bulb, electrotherapy and medicines. The basis of operative treatment is flap surgery. The anatomical result of 1000 (velo) pharyngoplasties carried out in Madarász and Heim Pál Children's Hospital (Budapest) is good in 98%, the hyperrhinophony ceased or became minimal in 90% after surgery. The ideal age for operation is 4.5 years.


Effects of leg muscle fatigue on gait in patients with Parkinson's disease and controls with high and low levels of daily physical activity.
Patients with Parkinson's disease (PD) are more susceptible to muscle fatigue, which can damage their gait. Physical activity can improve muscle condition, which is an important aspect during walking. The aim of this study was to analyze the effects of lower limb muscle fatigue on gait in patients with PD and healthy individuals, grouped according to physical activity level. Twenty Patients with PD (PD group) and 20 matched individuals (control group) were distributed according to physical activity level into four subgroups of ten individuals (active and inactive). Participants performed three walking trials before and after lower limb muscle fatigue, induced by a repeated sit-to-stand task on a chair. Kinematic (stride length, width, duration, velocity and percentage of time in double support) and kinetic (propulsive and breaking anterior-posterior and medio-lateral impulse) gait parameters were analyzed. In both groups, participants increased stride length and velocity and decreased stride duration and braking vertical impulse after lower limb muscle fatigue. The PD groups presented higher step width and percentage of double time support than the control groups before muscle fatigue. The control groups increased step width and decreased percentage of time in double support, while the PD groups did not change these parameters. For physical activity level, active individuals presented longer stride length, greater stride velocity, higher braking and propulsive anterior-posterior impulse and shorter step width than inactive individuals. Groups sought more balance and safety after lower limb muscle fatigue. Physical activity level does not appear to modify the effects of lower limb muscle fatigue during unobstructed walking in individuals with PD or controls.


Rapid antigen test to identify COVID-19 infected patients with and without symptoms admitted to the Emergency Department.
Early detection of SARS-CoV-2 patients is essential to contain the pandemic and keep the hospital secure. The rapid antigen test seems to be a quick and easy diagnostic test to identify patients infected with SARS-CoV-2. To assess the possible role of the antigen test in the Emergency Department (ED) assessment of potential SARS-CoV-2 infection in both symptomatic and asymptomatic patients. Between 1 July 2020 and 10 December 2020, all patients consecutively assessed in the ED for suspected COVID-19 symptoms or who required hospitalisation for a condition not associated with COVID-19 were subjected to a rapid antigen test and RT-PCR swab. The diagnostic accuracy of the antigen test was determined in comparison to the SARS-CoV-2 PCR test using contingency tables. The possible clinical benefit of the antigen test was globally evaluated through decision curve analysis (DCA). A total of 3899 patients were subjected to antigen tests and PCR swabs. The sensitivity, specificity and accuracy of the antigen test were 82.9%, 99.1% and 97.4% (Cohen's K = 0.854, 95% CI 0.826-0.882, p < 0.001), respectively. In symptomatic patients, sensitivity was found to be 89.8%, while in asymptomatic patients, sensitivity was 63.1%. DCA appears to confirm a net clinical benefit for the preliminary use of antigen tests. The antigen test performed in the ED, though not ideal, can improve the overall identification of infected patients. While it appears to perform well in symptomatic patients, in asymptomatic patients, although it improves their management, it seems not to be definitive.


Production of penile veno-occlusive insufficiency by arterial occlusion in a canine model.
Angiographic evaluation of impotent men revealed a frequent association between penile arterial disease and veno-occlusive insufficiency of the corpora cavernosa. In order to evaluate a possible cause-and-effect relationship, we investigated the competence of the cavernosal veno-occlusive mechanism in a canine model at various intervals after onset of cavernosal ischemia. In most dogs, the veno-occlusive mechanism could no longer be activated by papaverine after about 30 minutes of ischemia. If ischemia was relieved shortly thereafter, veno-occlusive competence returned after a further delay of one or two hours. The evidence suggests that veno-occlusive failure is not simply a hemodynamic consequence of loss of arterial inflow, but instead secondary to some ischemic injury. We conclude that arterial insufficiency may be one of the causes of cavernosal veno-occlusive insufficiency in humans.


Neural mechanism of priming in visual search.
Selective attention affords scrutinizing items in our environment. However, attentional selection changes over time and across space. Empirically, repetition of visual search conditions changes attentional processing. Priming of pop-out is a vivid example. Repeatedly searching for the same pop-out search feature is accomplished with faster response times and fewer errors. We review the psychophysical background of priming of pop-out, focusing on the hypothesis that it arises through changes in visual selective attention. We also describe research done with macaque monkeys to understand the neural mechanisms supporting visual selective attention and priming of pop-out, and survey research on priming of pop-out using noninvasive brain measures with humans. We conclude by hypothesizing three alternative neural mechanisms and highlighting open questions.


New approach for assessing human perfluoroalkyl exposure via hair.
In the recent years hair has been increasingly used as alternative matrix in human biomonitoring (HBM) of environmental pollutants. Sampling advantages and time integration of exposure assessment seems the most attractive features of hair matrix. In the current study, a novel miniaturized method was developed and validated for measuring 15 perfluoroalkyl substances (PFAS), including perfluoro n-butanoic acid (PFBA), perfluoro n-pentanoic acid (PFPeA), perfluoro n-hexanoic acid (PFHxA), perfluoro n-heptanoic acid (PFHpA), perfluor n-octanoic acid (PFOA), perfluoro n-nonanoic acid (PFNA), perfluoro tetradecanoic acid (PFTeDA), perfluorobutane sulfonic acid (PFBS), perfluoro pentane sulfonic acid (PFPeS), perfluorohexane sulfonic acid (PFHxS), perfluoroheptane sulfonic acid (PFHpS), perfluorooctane sulfonic acid (PFOS), perfluorononane sulfonic acid (PFNS), perfluorodecane sulfonic acid (PFDS) and perfluorododecane sulfonic acid (PFDoS) in human hair by liquid chromatography tandem mass spectrometry (LC-MS/MS). After extraction using ethyl acetate, dispersive ENVI-Carb was used for clean-up. Good intra- and inter-day precision for low (LQ 5 ng/g hair) and high spike (HQ 15n g/g) levels were achieved (in general RSD <10%). The accuracy was assessed using recoveries (%), which ranged between 68-118% (LQ) and 70-121% (HQ). The instrumental limit of detection (LODi) and limit of quantification (LOQi) were between 1-4 pg/g hair and 3-13 pg/g hair, respectively. The method limit of quantification (LOQm) ranged between 6 and 301 pg/g hair. The PFAS levels were measured in 30 human hair samples indicating that the levels are low (14-1534 pg/g hair). Some PFAS were not present in any hair sample (e.g. PFHpA, PFTeDA, PFNA, PFPeS, PFHpS, PFOS and PFNS), while other PFAS were frequently detected (PFBA, PFPeA, PFHxA, PFOA, PFBS, PFHxS, PFOS, PFDS and PFDoS) in human hair. Although levels in general were low, there is evidence of higher human exposure to some analytes, such as PFBA, PFPeA, PFHxA, PFOA, PFBS, PFHxS, and PFDoS. The current study shows that hair is a suitable alternative non-invasive matrix for exposure assessment of PFAS.


The septo-hippocampal pathway in patients suffering from senile dementia of Alzheimer's type. Evidence for neuronal plasticity?
In 7 cases of senile dementia of Alzheimer's type (SDAT) and in 7 age-matched controls, nerve cells of the medial septal nuclei (area CH1) and of the vertical limb of the diagonal band of Broca (area CH2) of the right hemisphere were counted in Cresyl-fast-violet-stained serial sections. The granular cells of the ipsilateral fascia dentata were Golgi-stained and dendritic spine density was quantified in 10-micron segments. There was a significant loss of neurons in areas CH1 and CH2 in SDAT cases compared to controls. The spine density of the granular cell dendrites was significantly reduced in the distal parts of the dendrites. In the most proximal part, where cholinergic septal fibers form synapses, the spine density was not significantly different between the two groups. We assume that collateral sprouting of undamaged inputs occurs maintaining a constant number of spines in the proximal segments despite the loss of source neurons within CH1 and CH2.


Relationship of equol production between children aged 5-7 years and their mothers.
The factors responsible for the production of isoflavone metabolites have not yet been identified. We aimed to examine the relationships of equol production between mother and child in a birth cohort in Japan. Subjects were a part of the participants in a longitudinal study on pregnant women and their offspring. When children were 5-7 years old, mothers and children were asked to reply to a questionnaire on lifestyles and a 3-day child's dietary record. Mothers and children were given a bar-shaped soy snack (Soyjoy®) daily on two consecutive days (soy challenge). The snack contained 14 mg of overall soy isoflavones as the sum of aglycones and the glucosides for mothers and 7.5 mg for children. On the morning of day 0 and 3, they were asked to mail their first-void urines. Urinary isoflavone metabolites of 159 mother-child pairs were measured by a high-performance liquid chromatography method. Equol producers were 35.5 % among mothers and 13.8 % among children. Equol producer status of a child was neither associated with dietary intake nor with urinary levels of daidzein and genistein. After multiple adjustments for potential confounders, the estimated relative risk of equol producer was 2.75 (95 % confidence interval 1.00, 7.52) among children whose mother was an equol producer, compared with children whose mother was a non-producer. Child's equol production was associated with the mother's equol producer status. The effects of maternal factors on child's equol production should be studied further.


A systematic review of the effect of performance-based financing interventions on out-of-pocket expenses to improve access to, and the utilization of, maternal health services across health sectors in sub-Saharan Africa.
Performance-based financing (PBF) assumes that subsidizing user fees for maternal health services to reduce out-of-pocket expenses will expand coverage and reduce inequities in access to maternal health services. It is usually associated with process changes, and the idea that increasing a facility's resources from PBF interventions can improve the availability of equipment, drugs, and medical supplies at the facility, has an indirect effect on out-of-pocket expenses. Assessment of complex interventions such as PBF requires consideration of specific underlying assumption or theories of change. Such assessment will allow a better and broader understanding of the system's strengths and weaknesses, where the gaps lie, whether the theory of change is sound, and will inform policy design and implementation. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) checklist, we performed a systematic review and a critical appraisal of selected studies using the risk-of-bias criteria developed by the Cochrane Effective Practice and Organisation of Care. We used the Grading of Recommendation and Evaluation, Development and Assessment framework for assessing the overall strength of the evidence. After the abstract screening (n = 9873), we deemed 302 as relevant for full-text screening and assessed 85 studies for review eligibility. Finally, we included 17 studies in the review. We could not conduct a meta-analysis, so we report a narrative synthesis. As an add-on to an existing payment mechanism, PBF may facilitate the removal of operational barriers to enhance utilization of certain maternal health services in some contexts, especially in public facilities. PBF strategies may potentially decrease out-of-pocket expenses for specific maternal health services, especially in settings that have already instituted some form of user fee exemption policies on maternal health services. The implementation of PBF can be considered a potential access instrument in reducing out-of-pocket expenses to stimulate demand for maternal services. However, the implementation approaches employed will determine utilization, taking into consideration existing equitable and inequitable access characteristics which vary by context. PROSPERO CRD42020222893.


Surgical treatment of inflammatory bowel disease--a review of some current opinions and controversies.
There are many controversial issues regarding the treatment of patients with inflammatory bowel disease. From this review we have concluded that the longer surgery for Crohn's disease is delayed, the higher the rate is of pre- and postoperative complications. A plea is thus made for relatively early surgical intervention. For Crohn's disease, the general policy today is to perform resections, even if relatively limited ones, rather than to perform by-passes of the macroscopically involved intestine. Indeterminate colitis, as well as self-limiting colitis, are differential diagnoses that the surgeon must be aware of, especially when selecting the appropriate operative method. Due to the existent risk of cancer in ulcerative colitis, some authors advocate prophylactic colectomy after 10 to 15 years, but the most current policy seems to be one of close surveillance, with surgery only in the cases of severe dysplasia or if a so called dysplasia associated lesion or mass (DALM) is diagnosed. Coloproctectomy has been the standard procedure for patients with ulcerative colitis, however, good or even excellent results are often seen after ileorectal anastomosis and pelvic pouch operations. Although all patients cannot benefit from the latter operation it is likely that it will become the principal operation for patients with ulcerative colitis.


Memory for word location during reading: eye movements to previously read words are spatially selective but not precise.
In two experiments, readers' use of spatial memory was examined by asking them to determine whether an individually shown probe word had appeared in a previously read sentence (Experiment 1) or had occupied a right or left sentence location (Experiment 2). Under these conditions, eye movements during the classification task were generally directed toward the right, irrespective of the location of the relevant target in the previously read sentence. In two additional experiments, readers' knowledge of prior sentence content was examined either without (Experiment 3) or with (Experiment 4) an explicit instruction to move the eyes to a target word in that sentence. Although regressions into the prior sentence were generally directed toward the target, they rarely reached it. In the absence of accurate spatial memories, readers reached previously read target words in two distinct steps--one that moved the eyes in the general vicinity of the target, and one that homed in on it.


NKL-24: A novel antimicrobial peptide derived from zebrafish NK-lysin that inhibits bacterial growth and enhances resistance against Vibrio parahaemolyticus infection in Yesso scallop, Patinopecten yessoensis.
The extensive use of antibiotics in aquaculture has resulted in the prevalence of antibiotic-resistant bacteria and, consequently, new antibacterial strategies or drugs with clear modes of action are urgently needed. Antimicrobial peptides (AMPs) are currently widely considered as alternatives to antibiotics in the treatment of infections in aquatic animals. In this study, we aimed to evaluate the effects of NKL-24, a truncated peptide derived from zebrafish NK-lysin, against Yesso scallop (Patinopecten yessoensis) pathogen, Vibrio parahaemolyticus. The results showed that NKL-24 had a potent antibacterial effect against V. parahaemolyticus via a membrane active cell-killing mechanism. The in vitro study showed that sub-lethal levels of NKL-24 obviously reduced bacterial swimming ability and downregulated the transcription of the selected genes associated with V. parahaemolyticus virulence. Studies on NKL-24 biosafety in hemocytes and in Yesso scallop have shown no adverse effects from this peptide. Bacteria challenge test results demonstrated that NKL-24 significantly decreased the mortality and inhibited bacterial growth in the scallop infected with V. parahaemolyticus, while further in vivo examination revealed that NKL-24 could enhance non-specific immune parameters. Moreover, NKL-24 was capable of modulating a series of V. parahaemolyticus-responsive genes in the scallop. These results suggest the protective action of NKL-24 against V. parahaemolyticus and the potential of this peptide as a promising candidate for aquaculture applications.


Influence of livestock activities on residue antibiotic levels of rivers in Hong Kong.
Occurrence of 10 antibiotics in the Yuen Long (YLR), Kam Tin (KTR), and Shing Mun (SMR) rivers of Hong Kong and possible influence of livestock activities on the concentrations of antibiotics were investigated. Tetracycline (30-497 ng/L), sulfadiazine (2-80 ng/L), sulfamethoxazole (2-152 ng/L), ofloxacin (5-227 ng/L), and erythromycin (1-315 ng/L) were detected in all the three rivers; chlortetracycline (23-227 ng/L), oxytetracycline (7-104 ng/L), ciprofloxacin (12-68 ng/L), and roxithromycin (1-105 ng/L) were detected in YLR and KTR, whereas norfloxacin (3-34 ng/L) was detected in KTR only. Significant correlation between livestock population and antibiotic contamination was observed in YLR only, indicating the influences of other sources in KTR and SMR. Among the antibiotics, significant correlation was observed between tetracyclines and sulfonamides indicating the major influence of livestock farms, whereas tetracyclines/sulfonamides were negatively correlated with fluoroquinolones/macrolides implying the differential origin of the latter class of antibiotics. Water quality of KTR and YLR were highly influenced by the non-point source pollutions, while of SMR was relatively good. Particularly, Escherichia coli populations of the YLR and KTR were 3-4 logs higher than those of the SMR indicating the involvement of livestock farms and sewerages. Good correlation between tetracyclines (TCs)/sulfonamides (SAs) and number of livestock farms and a negative correlation between TCs/SAs and fluoroquinolones (FQs)/macrolides (MLs) could be used as an indicator to trace the possible source of pollution.


Characterizing the response of a scintillator-based detector to single electrons.
Here we report the response of a high angle annular dark field scintillator-based detector to single electrons. We demonstrate that care must be taken when determining the single electron intensity as significant discrepancies can occur when quantifying STEM images with different methods. To account for the detector response, we first image the detector using very low beam currents (∼8fA), and subsequently model the interval between consecutive single electrons events. We find that single electrons striking the detector present a wide distribution of intensities, which we show is not described by a simple function. Further, we present a method to accurately account for the electrons within the incident probe when conducting quantitative imaging. The role detector settings play on determining the single electron intensity is also explored. Finally, we extend our analysis to describe the response of the detector to multiple electron events within the dwell interval of each pixel.


In vivo and in vitro effects of cadmium on selected enzymes in different organs of the fish Barbus conchonius Ham. (rosy barb).
1. Enzyme modulation by cadmium in selected organs of the fish, Barbus conchonius (rosy barb), was investigated in vivo (48 hr exposure to 12.6 mg/l cadmium chloride) and in vitro (10(-6) M cadmium chloride). 2. The acetylcholinesterase (AchE) activity was depressed in the gills but stimulated in the skeletal muscles and brain in vivo. The hepatic, branchial, and renal acid phosphatase (AcP) activity decreased marginally in vivo but it was significantly increased in the gut and ovary. In vitro, except for the liver, the AcP activity was depressed in the selected organs. Collaterally, gut alkaline phosphatase (AlP) was significantly inhibited but a pronounced stimulation was noted in the kidneys and ovary in vivo. In vitro, the AlP activity was conspicuously elevated in the kidneys and gut, and moderately in the gills. 3. Cadmium inhibited the glutamate-oxaloacetate and glutamate-pyruvate transaminases (GOT and GPT) in the liver, gills and kidneys in vivo. In vitro, the GOT and GPT activities were decreased in the liver, gills and kidneys. The lactic dehydrogenase (LDH) was significantly stimulated by Cd in the heart in vivo but in vitro the metal inhibited the enzyme in the gills. 4. Enzymes in the liver, followed by those in the kidneys and gills seem to be most seriously affected by Cd poisoning in this fish.


Clinicopathologic features of scrotal leiomyosarcoma: single institutional experience of ten cases.
Scrotal leiomyosarcoma arises from the subcutaneous smooth muscle layer and is an exceptionally rare disease process, with only six patients in the largest reported case series. This rarity creates uncertainties regarding diagnosis, surgical management, and clinical outcomes. Our purpose was to retrospectively describe our institutional experience with scrotal leiomyosarcoma from 2010 to 2022. Slides were reviewed with case inclusion requiring both nuclear atypia and mitotic activity. Ten patients with scrotal leiomyosarcoma were identified. Clinical impression included scrotal cyst in nine cases. The median age at diagnosis was 52 years (range: 29-75 years). The mean tumor size was 1.6 cm (range: 0.4-3.7 cm). Margins were positive in three cases and close in one case, prompting four re-excisions. The mean mitotic rate was 2.3 per 10 high-power field (range: 1-11), with mean Ki67 of 4.6% (range: 1-15%). Nine of the tumors were grade 1, while 1 was grade 2. Four patients had disease-specific follow-up. The remaining six patients have not had disease-specific surveillance. None of the ten patients have shown evidence of recurrence (median follow-up: 75 months, range: 0-116 months). Our series demonstrates that scrotal leiomyosarcoma has a deceptive clinical presentation with a wide age range and small tumor size. With complete surgical resection, scrotal leiomyosarcoma has an excellent prognosis and rigorous follow-up or adjuvant treatment is not likely to be necessary. Cases with unusual clinical or pathologic findings, such as large tumor size or high mitotic rate, may merit more intensive disease-specific surveillance.


The tetramerization domain of the tree shrew p53 protein displays unique thermostability despite sharing high sequence identity with the human p53 protein.
The p53 protein plays a number of roles in protecting organisms from different genotoxic stresses and this includes DNA damage induced by acetaldehyde, a metabolite of alcohol. Since the common tree shrew ingests high levels of alcohol as part of its normal diet, this suggests that its p53 protein may possess unique properties. Using a combination of biophysical and modeling studies, we demonstrate that the tetramerization domain of the tree shrew p53 protein is considerably more stable than the corresponding domain from humans despite sharing almost 90% sequence identity. Based on modeling and mutagenesis studies, we determine that a glutamine to methionine substitution at position 354 plays a key role in this difference. Given the link between stability of the p53 tetramerization domain and its transcriptional activity, the results suggest that this enhanced stability could lead to important consequences at p53-regulated genes in the tree shrew.


Socio-cultural Adaptation and Validation of Ages and Stages Questionnaire (ASQ 3) in Indian Children Aged 2 to 24 Months.
To socio-culturally adapt and validate a Hindi language version of ASQ-3 in Indian children aged 2-24 months. This cross-sectional study was conducted at a tertiary-care center between March, 2017 and April, 2019. Children "at-risk" for developmental delay of either gender aged 2-24 months. Socio-cultural adaptation was done through interaction among 37 subject experts followed by validation. After piloting in 20 children, modified ASQ-3 was validated in 568 at-risk children (4 age-groups: 2-7, 7-13, 13-19 and 19-24 months). Validation was done against Development assessment scale for Indian infants (DASII). Results: After screening 654 children, 568 were enrolled. Among these, 420 had developmental delay on DASII while 18 failed to be identified on ASQ (4.3%). Overall sensitivity and specificity of Hindi language Indian-adaptation of ASQ-3 in detecting developmental delay were 95.9% (95%CI: 93.6%-97.5%) and 81.7% (95%CI: 74%-87.9%), respectively with a positive predictive value (PPV) of 94.6% (95%CI: 92%-96.5%) and negative predictive value (NPV) of 85.6% (95%CI: 78.2%-92.2%). The sensitivity and specificity for motor delay were 96.1% (93.8%-97.7%) and 92.4% (86.4%-96.3%) [PPV: 97.7% (95.8%-98.9%); NPV: 87.7% (81%-92.7%)]. Sensitivity and specificity for mental delay were 95.5% (93.1%-97.2%)and 95.3% (90.1%-98.3%) [PPV: 98.6% (97%-99.5%); NPV: 85.9% (79.1%-91.2%)]. The Hindi language Indian-adaptation of ASQ-3 had good psychometric properties with high sensitivity for developmental delay (95.9%), mental delay (95.5%), and motor delay (96.1%), suggesting it to be a good screening tool for neurodevelopmental delay.


Is arterial stiffness a contributing factor to atrial fibrillation in patients with hypertension? A preliminary investigation.
Atrial fibrillation (AF) is the most common tachyarrhythmia encountered by clinicians. When AF occurs in patients with structural disorders, hypertension is most common. Hypertension may provoke or enable AF to occur through several mechanisms. One could be the resultant effects of increased afterload on the left ventricle and consequent changes in the left atrium. The latter could be the direct linear effect of elevated diastolic atrial pressure and its proximate effect on atrial electrophysiology. Alternatively, it may be a more indirect and complex relationship involving chronic morphologic, electrophysiologic, and secretory consequences in the atrium consequent to a chronically reduced left ventricular (LV) compliance. To assess this relationship, the arterial stiffness index (ASI) was determined in 53 hypertensive patients (29 with AF, 24 without) and 17 nonhypertensive controls with AF and its relationship to ventricular hypertrophy and AF was determined. All except 5 patients with AF had paroxysmal AF (PAF); the other 5 were in sinus rhythm status after cardioversion of a persistent AF episode. The ASI was significantly higher in patients with hypertension, both with and without AF than in lone AF patients, but did not distinguish between hypertensives with and without AF. The ASI was higher in the presence of LV hypertrophy (LVH). The ASI and LVH cannot be used to predict the risk of AF in hypertensive patients and the development of AF in hypertensives is more complex than just that of the immediate effect of elevated ventricular pressure on atrial pressure and stretch. Rather, AF is linked through the chronic alterations that are consequent to atrial hypertension.