POLYPOIDAL CHOROIDAL VASCULOPATHY ASSOCIATED WITH SECTOR RETINITIS PIGMENTOSA.
To report a case of polypoidal choroidal vasculopathy associated with sector retinitis pigmentosa. Case report. A 63-years-old woman presented with complaints of having painless progressive reduction of vision in the left eye (LE) for the past 6 months. On examination, her best-corrected visual acuity was 20/20 in the right eye and 20/125 in the LE. Based on fundus examination and multimodal imaging findings, both eyes were diagnosed to have sector retinitis pigmentosa, and an associated active extramacular polypoidal choroidal vasculopathy was seen in the LE. Spectral-domain optical coherence tomography also revealed choroidal thinning in both eyes. Patient underwent bevacizumab injection in the LE. At 1-month posttreatment, her best-corrected visual acuity remained stable in the LE, and spectral-domain optical coherence tomography showed reduction in subretinal fluid and size of the polypoidal lesion. Polypoidal choroidal vasculopathy, a pachychoroid disease, could occur in association with retinitis pigmentosa, in the setting of thin choroids, and multimodal imaging is important to differentiate it from Type-1 macular neovascularization.


Establishment, characterization, and cryopreservation of cell lines derived from red-rumped agouti (Dasyprocta leporina Linnaeus, 1758) - A study in a wild rodent.
Somatic cells can be used for rescuing wild mammals of ecological and economic importance, such as red-rumped agouti, through their application in advanced technologies. Thus, appropriate cell isolation, culture, and storage through cryopreservation can ensure the future safe use of these cells. We aimed to establish and evaluate the effects of culture time (second, fifth, and eighth passages) and cryopreservation on the morphology, viability, metabolism, proliferative activity, reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔΨm), and apoptosis on somatic cells derived from red-rumped agouti skin. Initially, we identified six dermal fibroblast lines by morphology, immunophenotyping, and karyotyping assays. In vitro culture after the second, fifth, and eighth passages, as well as the cryopreservation conditions used did not affect the metabolism or level of apoptosis. Nevertheless, cells in the fifth passage featured a reduction in proliferative activity and an increase in ROS levels when compared to second and eighth passage cells. Moreover, cryopreservation resulted in reduced ΔΨm when compared to non-cryopreserved cells. Additionally, cryopreserved cells showed a reduction in viability immediately after thawing; nevertheless, the viability of these cells was re-established after 11 days of in vitro culture and was similar to that of non-cryopreserved cells. In conclusion, we have shown that viable fibroblasts can be obtained from red-rumped agouti skin, featuring minimal changes after eight passages in in vitro culture systems. Additionally, adjustments to the cryopreservation protocol are necessary to reduce cellular oxidative stress caused by low temperatures.


Inhibitory effects of treatment with an LHRH antagonist on the ovulatory cycle are reduced when administered during the late follicular phase.
To compare the effects of transitory suppression of pituitary gonadotropin secretion by an LHRH antagonist at the mid or late follicular phase of the menstrual cycle, adult macaques with normal menstrual cycles were treated with an LHRH antagonist (N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Trp3,D-hArg(Et2)6,D-Ala10 ]LHRH (detirelix) administered subcutaneously at a dose of 300 micrograms/kg, daily for 3 days beginning either during the mid or late follicular phase. In all eight animals treated during the mid follicular phase, serum concentrations of LH and FSH declined and remained suppressed for 4 days. This caused a fall in serum concentrations of estradiol and the expected ovulation failed to occur. During the recovery period a marked rise in serum FSH occurred followed by normal follicular development and ovulation 14.8 +/- 0.6 days after the last injection of antagonist. Of the 9 macaques given the same treatment during the late follicular phase, only in two was the expected rise in serum progesterone prevented. In 4 of the animals a transitory suppression in LH and estradiol was observed but this was followed by a recovery and occurrence of an LH surge and rise in serum progesterone indicating ovulation during the course of treatment. In the remaining 3 macaques treatment commenced on the day of the initiation of the LH surge and was associated with a progesterone rise of normal duration but lower than normal magnitude during the early luteal phase. These results show that LHRH antagonist treatment causes rapid inhibition of pituitary-ovarian function when administered up to the mid follicular phase of the cycle and is effective in blocking ovulation. The suppressive effects of the antagonist are reduced when administered during the late follicular phase. This may be due to decreased dependence of the pituitary gonadotrope on LHRH at this time and on decreased dependence of the dominant follicle on the gonadotropins.


Predictors of neonatal adiposity and associations by fetal sex in women with gestational diabetes mellitus and normal glucose-tolerant women.
To determine predictors of neonatal adiposity and differences in associations by fetal sex in women with gestational diabetes mellitus (GDM), normal-weight and overweight (BMI ≥ 25 kg/m2) normal glucose-tolerant women (NGT). Skinfold thickness was measured in 576 newborns, and cord blood leptin, c-peptide and lipids in 327 newborns in a multi-centric prospective cohort study. Compared to neonates of normal-weight NGT women (327), neonates of women with GDM (97) were more often large-for-gestational age (LGA) (16.5% vs 8.6%, p = 0.024) ,but the macrosomia rate (8.2% vs 5.8%, p = 0.388), sum of skinfolds (13.9 mm ± 2.9 vs 13.3 mm ± 2.6, p = 0.067), neonatal fat mass (1333.0 g ± 166.8 vs 1307.3 g ± 160.9, p = 0.356), and cord blood biomarkers were not significantly different. Compared to neonates of normal-weight NGT women, neonates of overweight NGT women (152) had higher rates of macrosomia (12.5% vs 5.8%, p = 0.012), LGA (17.1% vs 8.6%, p = 0.006), higher sum of skinfolds (14.3 mm ± 2.6 vs 13.2 mm ± 2.6, p < 0.001), neonatal fat mass (1386.0 g ± 168.6 vs 1307.3 g ± 160.9, p < 0.001), % neonatal fat mass > 90th percentile (15.2% vs 7.1%, p < 0.001), without significant differences in cord blood biomarkers. Maternal BMI, fasting glycemia, triglycerides, gestational weight gain, cord blood leptin ,and cord blood triglycerides were independent predictors for neonatal adiposity. Gestational weight gain was positively associated with adiposity in boys only. Compared to neonates of normal-weight NGT women, neonates of GDM women have higher LGA rates but similar adiposity, while neonates of overweight NGT women have increased adiposity. Limiting gestational weight gain might be especially important in the male fetus to reduce neonatal adiposity.


[The dynamic change of mercury concentration in urine after amalgam filled].
Through the regular examination of mercury concentration in urine this study was to observe the dynamic change of the mercury concentration in the patients with amalgam fillings so as to find out the effect of amalgam on health. Determine the mercury concentration of the patients in urine after amalgam filled regularly serving the mercury concentration of the patients in urine before amalgam filled as self control to observe the dynamic change of the mercury concentration in patients with amalgam fillings. It was found that mercury concentration in urine went up distinctly 1 day after amalgam filled dropped slightly 1 week after amalgam filled fell obviously and resumed almost to the baseline 2 weeks after amalgam filled set at the baseline 4 8 weeks and 1 year after amalgam filled. Amalgam don't have clear side effect on health based on the mercury concentration in urine.


An Appraisal on Prominent Industrial and Biotechnological Applications of Bacterial Lipases.
Microbial lipases expedite the hydrolysis and synthesis of long-chain acyl esters. They are highly significant commercial biocatalysts to biotechnologists and organic chemists. The market size of lipase is anticipated to reach $590 million by 2023. This is all owing to their versatility in properties, including stability in organic solvents, interfacial activation in micro-aqueous environments, high substrate specificity, and activity in even non-aqueous milieu. Lipases are omnipresent and synthesized by various living organisms, including animals, plants, and microorganisms. Microbial lipases are the preferred choice for industrial applications as they entail low production costs, higher yield independent of seasonal changes, easier purification practices, and are capable of being genetically modified. Microbial lipases are employed in several common industries, namely various food manufactories (dairy, bakery, flavor, and aroma enhancement, etc.), leather tanneries, paper and pulp, textiles, detergents, cosmetics, pharmaceuticals, biodiesel synthesis, bioremediation and waste treatment, and many more. In recent decades, circumspection toward eco-friendly and sustainable energy has led scientists to develop industrial mechanisms with lesser waste/effluent generation, minimal overall energy usage, and biocatalysts that can be synthesized using renewable, low-cost, and unconventional raw materials. However, there are still issues regarding the commercial use of lipases which make industrialists wary and sometimes even switch back to chemical catalysis. Industrially relevant lipase properties must be further optimized, analyzed, and explored to ensure their continuous successful utilization. This review comprehensively describes the general background, structural characteristics, classifications, thermostability, and various roles of bacterial lipases in important industries.


Green synthesis of chitooligosaccharide-PEGDA derivatives through aza-Michael reaction for biomedical applications.
Chitooligosaccharide (COS) as an emerging material carbohydrate polymer with huge potential in biomedical applications was prepared using a microwave-assisted process. The obtained COS exhibited reduced molecular weight (Mw) and higher water solubility in comparison to chitosan while preserving the main saccharide structure and same degree of deacetylation (DD). The optimized COS (13 kDa) was then used to synthesize a new family of COS-poly(ethylene glycol) diacrylate (PEGDA) derivatives based on aza-Michael addition of acrylate groups of PEGDA to the amine groups of COS in the absence of any exterior agents. The modulation of the reaction time, temperature, pH and NH2:acrylate molar ratio, had a strong influence on the Michael reaction progress. At higher degrees of conversion of acrylate groups, COS-PEGDA derivative formed gel with high biocompatibility towards human bone mesenchymal stem cells (hBMSCs). These COS-PEGDA hydrogels synthesized at mild conditions through a green chemistry are, therefore, an innovative system combining adequate biological performance, ease of preparation, and an environmentally friendly concept of production.


Removing noises caused by motion artefacts in microcirculation maps of human skin in vivo.
This paper presents a zero-padding and cross-correlation technique-based correlation mapping optical coherence tomography (ZPCC-cmOCT) to reconstruct microcirculation maps of human skin in vivo, which can remove the background decorrelation noise caused by motion artefacts. In conventional correlation mapping optical coherence tomography method, the correlation degree of static tissue may be lowered by the motion artefacts due to cardiac and respiratory motion, resulting in background decorrelation noise in microcirculation maps. In zero-padding and cross-correlation technique-based correlation mapping optical coherence tomography method, structural images are first obtained by performing Fourier transform on zero-padded interference fringes, and then cross-correlation-based image registration is utilized to align local areas in two adjacent structural images. Finally, correlation mapping optical coherence tomography method is performed to generate microcirculation maps. Both phantom experiments and in vivo experiments were implemented and the results demonstrate that the proposed method is capable of providing microcirculation maps with the background decorrelation noise removed.


Primary malignant lymphoma of the urinary bladder: report of three cases and review of the literature.
We report three cases of a primary malignant lymphoma of the urinary bladder. The radiological features revealed a sessile mass of the lateral wall for one case, a circumferential thickening in the second, and two separated masses of the bladder wall in the last case. Primary malignant lymphoma of the urinary bladder is extremely rare. From a review of the literature, the clinical and radiological findings are discussed. In this paper we report the first case of urinary bladder lymphoma presented on CTas multiple masses.


Barriers to access to clinical trial data: Obstruction of a RIAT reanalysis of the treatment for adolescents with depression study.
Public access to data has been a major step in attempting to reduce bias in scientific literature. Data to verify efficacy outcomes are now more accessible; however, little has been done to ensure public access to harms data from RCTs, which are equally important in ascertaining possible misreporting and protecting safety. The treatment for adolescents with depression study (TADS) has influenced most international practice guidelines for treating children and adolescents with depression, supporting first-line prescription of fluoxetine in combination with cognitive behavioural therapy (CBT). However, after over 30 publications by the TADS team, reporting on harms remains highly deficient and we aimed to redress this lack. In undertaking a restoring invisible and abandoned trials (RIAT) reanalysis of TADS' effectiveness and safety outcomes, we sought access to de-identified serious adverse events (SAE) data. This paper describes our unsuccessful efforts to obtain more detailed SAE data from TADS' data custodians, highlighting several problematic blocks to comprehensive safety reporting. Comprehensive access to clinical trial data is necessary to ensure safe and fully informed guidelines for treating children and adolescents with depression.


Bioaccessibility of curcumin encapsulated in yeast cells and yeast cell wall particles.
This study evaluates the role of intracellular composition and integrity of cell walls in modulating the release and bioaccessibility of phytochemicals during simulated gastrointestinal digestion of cell-based carriers. Native yeast and yeast cell wall particles (YCWPs) were used as model cell-based carriers with distinct intracellular composition and curcumin was a model encapsulated bioactive. The results highlight the essential role of gastric treatments and the presence of bile salts in the release and bioaccessibility of encapsulated compound from cell-based carriers. YCWPs with significantly reduced intracellular contents have a significantly faster intestinal release after gastric digestion. Multimodal imaging approaches confirm the release of encapsulated curcumin in intestinal compartment without any significant changes in the cellular structure including cell walls. Based on these results, the study proposes a model that illustrate the significance of gastric digestion in influencing the release of curcumin during gastrointestinal digestion.


Comparison of the touch-screen and traditional versions of the Corsi block-tapping test in patients with psychosis and healthy controls.
Working memory (WM) refers to the capacity system for temporary storage and processing of information, which is known to depend on the integrity of the prefrontal cortex. Impairment in working memory is a core cognitive deficit among individuals with psychotic disorders. The Corsi block-tapping test is a widely-used instrument to assess visuospatial working memory. The traditional version is composed of 9 square blocks positioned on a physical board. In recent years, the number of digital instruments has increased significantly; several advantages might derive from the use of a digital version of the Corsi test. This study aimed to compare the digital and traditional versions of the Corsi test in 45 patients with psychotic disorders and 45 healthy controls. Both groups completed a neuropsychological assessment involving attention and working memory divided into the two conditions. Results were consistent between the traditional and digital versions of the Corsi test. The digital version, as well as the traditional version, can discriminate between patients with psychosis and healthy controls. Overall, patients performed worse with respect to the healthy comparison group. The traditional Corsi test was positively related to intelligence and verbal working memory, probably due to a more significant effort to execute the test. The digital Corsi might be used to enhance clinical practice diagnosis and treatment.The digital version can be administered in a natural environment in real-time. Further, it is easy to administer while ensuring a standard procedure.


Effect of different drying methods on product quality, bioactive and toxic components of Ginkgo biloba L. seed.
Ginkgo biloba seeds are used as a functional food across Asia. However, the presence of toxic compounds has limited their application. In this study, freeze drying, infrared drying, hot-air drying and pulsed-vacuum drying were used to dry G. biloba seeds. A comprehensive analysis was performed on their product quality, antioxidant activities, bioactive and toxic components. Results showed that the drying methods had a significant influence on product quality with freeze drying being superior due to the minimal microstructural damage, followed by infrared drying and pulsed-vacuum drying. Infrared-dried product possessed the strongest antioxidant activities and higher bioactive compound content than hot-air-dried and pulsed-vacuum-dried product. Toxic compounds in fresh G. biloba seeds (ginkgotoxin, ginkgolic acid and cyanide) were reduced markedly by drying. Ginkgotoxin was reduced fourfold, and the contents of acrylamide, ginkgolic acid and cyanide in dried G. biloba seeds were reduced to the scope of safety. Amongst the four drying methods, infrared drying had the shortest drying time, and its product showed higher quality and bioactive compound content, and stronger antioxidant activities. These findings will offer salient information for selecting a drying method during the processing of ginkgo seeds. Infrared drying could be considered as a multiple-effect drying method in the processing of ginkgo seeds. © 2020 Society of Chemical Industry.


Trends in microextraction approaches for handling human hair extracts - A review.
The complementary role of hair in testing scenarios has expanded across the spectrum of toxicological and clinical monitoring investigations and, over the last 20 years, hair analysis has gained increasing attention and recognition. Moreover, a great deal of attention has been paid to the miniaturisation of extraction procedures, minimising/eliminating toxic organic solvents consumption, making them user-friendly and rapid, in addition to maximising extraction efficiency. The aim of this work is to provide a critical review of the advances observed over the last 5 years in the use of miniaturised approaches for sample clean-up and drug pre-concentration in hair analysis. There have been major improvements in some well-established microextraction approaches, such as liquid phase microextraction, mainly through the use of supramolecular and ionic liquids. In addition, new developments have also been reported in solid phase microextraction, driven by d-SPE applications. In the last 5 years, a total of 69 articles have been published using some type of microextraction technique for hair specimens, thus justifying the relevance of a critical review of innovations, improvements and trends related to these miniaturised approaches for sample preparation.


Left prefrontal transcranial magnetic stimulation for treatment-resistant depression in adolescents: a double-blind, randomized, sham-controlled trial.
Treatment-resistant depression (TRD) is prevalent and associated with a substantial psychosocial burden and mortality. There are few prior studies of interventions for TRD in adolescents. This was the largest study to date examining the feasibility, safety, and efficacy of 10-Hz transcranial magnetic stimulation (TMS) for adolescents with TRD. Adolescents with TRD (aged 12-21 years) were enrolled in a randomized, sham-controlled trial of TMS across 13 sites. Treatment resistance was defined as an antidepressant treatment record level of 1 to 4 in a current episode of depression. Intention-to-treat patients (n = 103) included those randomly assigned to active NeuroStar TMS monotherapy (n = 48) or sham TMS (n = 55) for 30 daily treatments over 6 weeks. The primary outcome measure was change in the Hamilton Depression Rating Scale (HAM-D-24) score. After 6 weeks of blinded treatment, improvement in the least-squares mean (SE) HAM-D-24 scores were similar between the active (-11.1 [2.03]) and sham groups (-10.6 [2.00]; P = 0.8; difference [95% CI], - 0.5 [-4.2 to 3.3]). Response rates were 41.7% in the active group and 36.4% in the sham group (P = 0.6). Remission rates were 29.2% in the active group and 29.0% in the sham group (P = 0.95). There were no new tolerability or safety signals in adolescents. Although TMS treatment produced a clinically meaningful change in depressive symptom severity, this did not differ from sham treatment. Future studies should focus on strategies to reduce the placebo response and examine the optimal dosing of TMS for adolescents with TRD.


[Therapeutic results achieved in 1366 patients with corpus uteri carcinomas treated between 1946 and 1972].
A report is given on 1366 patients with tumour of the uterine body. A computer was used for evaluation purposes. The 5-year survival rate relating to all stages of the disease was 62.37%. The best results were obtained when surgery was combined with irradiation therapy.


A new Otogelin ENU mouse model for autosomal-recessive nonsyndromic moderate hearing impairment.
Approximately 10 % of the population worldwide suffers from hearing loss (HL) and about 60 % of persons with early onset HL have hereditary hearing loss due to genetic mutations. Highly efficient mutagenesis in mice with the chemical mutagen, ethylnitrosourea (ENU), associated with relevant phenotypic tools represents a powerful approach in producing mouse models for hearing impairment. A benefit of this strategy is to generate alleles to form a series revealing the full spectrum of gene function in vivo. It can also mimic the range of human mutations and polymorphisms for HL. In the course of a genome ENU mutagenesis program, we selected a new mouse model for hearing defect based on a dysmorphological screen. We identified by gene mapping the mutation responsible for this phenotype and characterized it at the histological level of the inner ear and evaluated the vestibule by following the recommendations of the standard operating procedures, IMPReSS. We have identified and characterized a new recessive allele of the otogelin gene, Otog (vbd/vbd) , due to a homozygous one base pair substitution at the splice donor site of intron 29. This mutation leads to a frame-shift and a premature stop codon. We observed a decrease in the amount of sensory cells in the maculae of Otog (vbd/vbd) mice as well as an apparent drastically decreased density to almost absence of the otoconial membrane. Compared to Otog (tm1Prs) and twister, the two other existing otogelin alleles, the detailed analysis of Otog (vbd/vbd) revealed that these mice share some common behavioural characteristics either with Otog (tm1Prs) or twister whereas the fine vestibular phenotype and the hearing defect are different. Our results emphasize the importance of detecting and characterizing a new allele of a gene in order to get comprehensive information about the gene function.


A randomized prospective study on the treatment of intra-articular distal radius fractures: open reduction and internal fixation with dorsal plating versus mini open reduction, percutaneous fixation, and external fixation.
To compare 2 methods of surgical treatment for displaced intra-articular fractures of the distal radius: open reduction and internal fixation with dorsal plating (Pi Plate; Synthes, Paoli, PA) versus mini open reduction with percutaneous K-wire and external fixation. Patients with AO type C intra-articular distal radius fractures were randomized into 2 groups: open reduction and internal fixation and dorsal plating or external fixation and K-wires and mini-open reduction. Patients over the age of 70 years with any associated soft-tissue or skeletal injury to the same limb and pre-existing wrist arthrosis or disability were excluded from the study. Objective, subjective, and radiographic outcomes were assessed at 2 weeks, 4 to 6 weeks, 10 to 12 weeks, 6 months, and 1- and 2-year intervals. The minimum follow-up period was 6 months; the average follow-up period was 18 months. The principal outcome analyzed was the Disabilities of the Arm, Shoulder, and Hand score. Secondary outcomes included grip strength, range of motion, surgical procedure time, complications, and radiographic parameters. The groups were equal with respect to age, gender, fracture subtype, and number of workers' compensation cases. No significant difference was found in the Disabilities of the Arm, Shoulder, and Hand scores, our primary outcome. The dorsal plate group, however, showed a higher complication rate when compared with the external fixator group. The plate group had significantly longer tourniquet times when compared with the external fixator group. The plate group also had higher levels of pain at 1 year when compared with the external fixator group; however, this equalized after hardware removal. The external fixator group showed an average grip strength of 97% compared with the normal side and 86% in the dorsal plate group. At midterm analysis the dorsal plate group showed a significantly higher complication rate compared with the external fixator group; therefore enrollment in the study was terminated. The dorsal plate group also showed statistically significant higher levels of pain, weaker grip strength, and longer surgical and tourniquet times. Based on these results we cannot recommend the use of dorsal plates in treating complex intra-articular fractures of the distal radius.


Antimicrobial and Antioxidant Activities of Endophytic Fungi Associated with Arrabidaea chica (Bignoniaceae).
The endophytic fungal community of the Amazonian medicinal plant Arrabidaea chica (Bignoniaceae) was evaluated based on the hypothesis that microbial communities associated with plant species in the Amazon region may produce metabolites with interesting bioactive properties. Therefore, the antimicrobial and antioxidant activities of the fungal extracts were investigated. A total of 107 endophytic fungi were grown in liquid medium and the metabolites were extracted with ethyl acetate. In the screening of fungal extracts for antimicrobial activity, the fungus identified as Botryosphaeria mamane CF2-13 was the most promising, with activity against E. coli, S. epidermidis, P. mirabilis, B. subtilis, S. marcescens, K. pneumoniae, S. enterica, A. brasiliensis, C. albicans, C. tropicalis and, especially, against S. aureus and C. parapsilosis (MIC = 0.312 mg/mL). Screening for antioxidant potential using the DPPH elimination assay showed that the Colletotrichum sp. CG1-7 endophyte extract exhibited potential activity with an EC50 of 11 µg/mL, which is equivalent to quercetin (8 µg/mL). The FRAP method confirmed the antioxidant potential of the fungal extracts. The presence of phenolic compounds and flavonoids in the active extracts was confirmed using TLC. These results indicate that two of the fungi isolated from A. chica exhibit significant antimicrobial and antioxidant potential.


An extensive field study reveals the circulation of new genetic variants of subtype 1a of bovine viral diarrhea virus in Uruguay.
Bovine viral diarrhea virus (BVDV) is a major pathogen worldwide, causing significant economic losses to the livestock sector. In Uruguay, BVDV seroprevalence at the farm level is >80%. In this work, 2546 serum, blood or tissue samples collected from animals suspected of being affected by BVD between 2015 and 2017 were analyzed by reverse transcription PCR and sequencing. Analysis of the BVDV genomic regions 5'UTR/Npro, Npro and E2 revealed that BVDV-1a, 1i and 2b circulate in the country, with BVDV-1a being the most prevalent subtype. Population dynamics studies revealed that BVDV-1a has been circulating in our herds since ~1990. This subtype began to spread and evolve, accumulating point mutations at a rate of 3.48 × 10-3 substitutions/site/year, acquiring specific genetic characteristics that gave rise to two local genetic lineages of BVDV-1a. These lineages are divergent from those circulating worldwide, as well as the vaccine strain currently used in Uruguay. The most notable differences between field and vaccine strains were found in the E2 glycoprotein, suggesting that the amino acid substitutions could result in failure of cross-protection/neutralization after vaccination. This is the first study that compares Uruguayan BVDV field and vaccine strains with other BVDV strains from throughout the world. The results obtained in this study will be very useful for developing a suitable immunization program for BVDV in Uruguay by identifying local field strains as candidates for vaccine development.


First detection of koi herpesvirus and carp oedema virus in Iraq associated with a mass mortality in common carp (Cyprinus carpio).
At the end of October 2018, a mass fish mortality occurred in Iraq, involving thousands of tons of cultured and wild common carp (Cyprinus carpio) along Euphrates and Tigris rivers. Fish were found dead or moribund along rivers coasts, showing lethargy, dyspnoea and flared gills. At necropsy, discoloration patches were noticed on the gills. Wet preparations showed rare metacercariae and Dactylogyrus spp. Samples were subjected to bacteriological tests and virological investigation through real-time PCR and nested PCR. Both were positive for koi herpesvirus (KHV) and carp oedema virus. Results obtained were confirmed by the OIE reference laboratory of KHV disease (KHVD) at Cefas (UK) and by sequence analysis. This is the first report on the detection of both viruses in Iraq.


Cholecalciferol (vitamin D 3) improves cognitive dysfunction and reduces inflammation in a rat fatty liver model of metabolic syndrome.
The aim of this study was to examine the effects of cholecalciferol on systemic inflammation and memory in the setting of fatty liver disease in rats. To induce the development of fatty liver disease, the rats were fed a 35% fructose solution over 8 weeks. Group I (n=6) was designated as the control group and fed with standard rat chow. Group II (n=6) was provided with, standard rat chow, and 0.3 μg/kg/day of oral cholecalciferol over a duration of 2 weeks. In addition to standard rat chow, group III (n=6) and group IV (n=6) were given 4 mL of the 35% fructose solution per day via oral gavage for 8 weeks. However, group IV was also given 0.3 μg/kg/day of oral cholecalciferol over 2 weeks. After the treatment period, passive avoidance tasks were performed by all groups. The liver and brain were harvested for subsequent biochemical and histopathologic analyses. The development of fatty liver extends the memory latency period of passively avoiding tasks after 1 trial. Moreover, there were increases in brain TNF-α and plasma MDA levels according to two-way analysis of variance. Cholecalciferol supplementation decreased the latency period of passively avoiding tasks in rats with hepatosteatosis, and also significantly reduced brain TNF-α and plasma MDA levels. Fatty liver may contribute to the development of systemic inflammation, which affects cognition and causes deficits in memory; however, the anti-inflammatory and antioxidant properties of vitamin D may improve the cognitive function of rats with hepatosteatosis.


Species Identification and Fungicide Sensitivity of Fungi Causing Alternaria Leaf Blight and Head Rot in Cole Crops in the Eastern United States.
Alternaria leaf blight and head rot is an important disease of broccoli and other cole crops. With no resistant host varieties, fungicides are utilized to manage this disease. However, anecdotal evidence suggests that, in southeastern U.S. broccoli-producing states, there is a loss of disease control through the use of quinone outside inhibitor (QoI) fungicides. To understand why there is a reduced sensitivity to QoI fungicides in these states, we isolated Alternaria spp. from symptomatic lesions on cole crops from Georgia and Virginia (two states with observations of loss of fungicide sensitivity) as well as New York (a state with no observations of loss of fungicide sensitivity). Using multilocus sequencing and phylogenetic analysis, we identified two species, Alternaria brassicicola and A. japonica. Whereas A. brassicicola was isolated in all states, A. japonica was only isolated in Georgia. Next, we wanted to determine the sensitivity of these isolates to azoxystrobin-an active ingredient in some QoI fungicides-by estimating the effective concentration at which only 50% of spores germinate (EC50). The EC50 of A. brassicicola ranged from 0.01 to 0.17 ppm, whereas that of A. japonica was 8.1 to 28.1 ppm. None of the known target-site mutations that confer resistance to QoI fungicides were identified during screening of either species. A. japonica was first reported on the east coast of the United States in 2020 in South Carolina. The substantially higher EC50 value suggests that its emergence in the southeastern United States may play at least a part in the observed loss of disease control. However, further in planta and field studies are needed to thoroughly test this hypothesis.


Associations between serum lipid levels and suicidal ideation among Korean older people.
There have been inconsistent reports on the relationships between lipids and suicidality, and studies conducted in older adults are rare. This study examined associations between serum lipid levels and suicidal ideation in an older population. This study used data obtained from a representative Korean sample of 4265 people age 65 years or older who completed a self-administered questionnaire about suicidal ideation over the last year. The fasting serum concentrations of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides were measured and categorized into lower, intermediate (reference), and upper quartiles. A complex sample logistic regression stratified by gender was performed to determine the associations between serum lipid levels and suicidal ideation after controlling for covariates including age, education, marital status, current smoking, alcohol drinking, body mass index, hypertension, diabetes, diagnosed depression, antidepressant use, and lipid-lowering therapies. In this study, the prevalence of suicidal ideation in an older Korean population was 22.9% (SE=0.9%). The prevalence was significantly higher in women than in men, 27.7% (1.2%) vs. 15.9% (1.1%) respectively. After adjusting for covariates, lower triglyceride levels were significantly associated with a decreased risk of suicidal ideation (OR=0.65; 95% CI=0.43-0.99) among men but no significant associations were observed among women. Additionally, there were no significant associations between any other measure of cholesterol levels and suicidal ideation in either men or women. Cross-sectional design cannot infer temporality or the effects of changes in variables. These results support the association between lower triglyceride levels and a reduced risk of suicidal ideation among Korean men over 65. Further studies are necessary to investigate gender difference and the biological mechanism.


Challenging diagnosis of Mycolicibacterium cosmeticum/canariasense infection: A case report and literature review.
We present the case of an immunocompromised child with Mycolicibacterium cosmeticum/ canariasense infection. Our case highlights the difficulty in adequate speciation. Most isolates described in the literature were identified using 16 s-rRNA PCR, which if performed on our sample would at best be inconclusive. Misidentifications could have a real impact on the body of evidence collected on these isolates thus far.


Using Response Times and Response Accuracy to Measure Fluency Within Cognitive Diagnosis Models.
The recent "Every Student Succeed Act" encourages schools to use an innovative assessment to provide feedback about students' mastery level of grade-level content standards. Mastery of a skill requires the ability to complete the task with not only accuracy but also fluency. This paper offers a new sight on using both response times and response accuracy to measure fluency with cognitive diagnosis model framework. Defining fluency as the highest level of a categorical latent attribute, a polytomous response accuracy model and two forms of response time models are proposed to infer fluency jointly. A Bayesian estimation approach is developed to calibrate the newly proposed models. These models were applied to analyze data collected from a spatial rotation test. Results demonstrate that compared with the traditional CDM that using response accuracy only, the proposed joint models were able to reveal more information regarding test takers' spatial skills. A set of simulation studies were conducted to evaluate the accuracy of model estimation algorithm and illustrate the various degrees of model complexities.


A chimeric SERM-histone deacetylase inhibitor approach to breast cancer therapy.
Breast cancer remains a significant cause of death in women, and few therapeutic options exist for estrogen receptor negative (ER (-)) cancers. Epigenetic reactivation of target genes using histone deacetylase (HDAC) inhibitors has been proposed in ER (-) cancers to resensitize to therapy using selective estrogen receptor modulators (SERMs) that are effective in ER (+) cancer treatment. Based upon preliminary studies in ER (+) and ER (-) breast cancer cells treated with combinations of HDAC inhibitors and SERMs, hybrid drugs, termed SERMostats, were designed with computational guidance. Assay for inhibition of four type I HDAC isoforms and antagonism of estrogenic activity in two cell lines yielded a SERMostat with 1-3 μM potency across all targets. The superior hybrid caused significant cell death in ER (-) human breast cancer cells and elicited cell death at the same concentration as the parent SERM in combination treatment and at an earlier time point.


Optimized Microscale Protein Aggregation Suppression Assay: A Method for Evaluating the Holdase Activity of Chaperones.
Many molecular chaperones act as holdases by binding hydrophobic regions of substrates to prevent aggregation. Therefore, measuring holdase activity is an amenable method to determine chaperone activity. The holdase function is reliably and easily achieved by monitoring the suppression of heat-induced aggregation of well-characterized model protein substrates. However, the standard assay format requires large amounts of protein and hence is not applicable to all proteins. Using DnaK from Escherichia coli and heat-induced aggregation of malate dehydrogenase, we describe a protocol for absorbance and fluorescence-based miniaturized versions of the standard aggregation suppression assay that are affordable and have wide application for low abundance holdases. The assay can be used for both fundamental characterization of holdase function in proteins and screening of inhibitors of holdase activity.


Kinetic studies of the reduction of yeast glutathione reductase by reduced nicotinamide hypoxanthine dinucleotide phosphate.
The reduction of yeast glutathione reductase by reduced nicotinamide hypoxanthine dinucleotide phosphate (NHxDPH) has been examined by stopped-flow kinetic methods. Like reduced glutathione or NADPH, this pyridine nucleotide generates the catalytically active two-electron reduced form of the enzyme. This reductive half-reaction with NHxDPH has only one detectable kinetic step which shows saturation kinetics (Kd = 76 microM), and has a limiting rate constant of 56 s-1. Comparison of stopped-flow and steady-state turnover data indicates that the reductive half-reaction is rate-limiting in the overall catalytic reaction. No evidence was found for a preequilibrium charge-transfer complex between NHxDPH and the active site FAD, like that seen when NADPH is the electron donor.


Angiotensin receptors: a new role in cancer?
There is increasing evidence that Angiotensin II (AngII), a major regulator of blood pressure and cardiovascular homeostasis, is involved in the regulation of cell proliferation, angiogenesis, inflammation and tissue remodeling, which suggests that this peptide might also play a role in cancer. This review focuses on the expression and function of Angiotensin I-converting enzyme (ACE) and AngII receptors in various aspects of cancer. Recent experimental data suggests that ACE inhibitors and AngII type 1 receptor (AT1R) antagonists have beneficial effects on tumor progression, vascularization and metastasis, and that the AngII type 2 receptor (AT2R) subtype has a potential role in cancer. An overview of the major intracellular signaling pathways associated with AT1R and AT2R activation in cancer cells, as well as in endothelial and inflammatory cells, is presented here.


Corrigendum: In a zebrafish biomedical model of human Allan-Herndon-Dudley syndrome impaired MTH signaling leads to decreased neural cell diversity.
[This corrects the article DOI: 10.3389/fendo.2023.1157685.].


Social support following bereavement: The role of beliefs, expectations, and support intentions.
Social support is one of the strongest determinants of bereavement outcomes, yet little is understood about the community's recognition of grief and intentions to provide social support to grieving persons. A total of 476 adults responded to an online vignette and questionnaire measuring grief norms and supportive intentions. Respondent gender, age, and bereavement status all had some association with expectations of grief, intentions to support, perceived helpfulness of support attempts, and opinions toward the diagnostic classification of grief. Given that most bereavement support is informal, this study informs the development of community capacity to provide constructive, timely bereavement support.


[Clinical study on effect of tuihuan decoction rectoclysis in hyperbilirubinemia of newborn].
To study the therapeutic effect and feasibility of rectoclysis with Tuihuang decoction (RTD) in treating hyperbilirubinemia of newborns. One hundred and seventy-five newborns with hyperbilirubinemia were randomly divided into the treated group and the control group. They were treated with western medicine plus double faced blue treatment while the treated group were given RTD additionally. Blood bilirubin was detected by micro-bilirubin detector daily during the treatment course. The time of jaundice regression, the speed of blood bilirubin reducing, liver function, and condition of rebounding were observed. The 7-day curative rate of jaundice in the treated group was superior to that in the control group, showing significant difference (P < 0.05). The average speed of blood bilirubin reducing daily in the treated group was quicker than that in the control group (P < 0.01). The improvement of liver function, such as AST, ALT and gamma-GT in the treated group was superior to that in the control group (P < 0.01). Rebound rate of blood bilirubin in the control group was significantly higher than that in the treated group (P < 0.05). RTD is an ideal therapy for treatment of hyperbilirubinemia of newborn, it shows obvious clinical efficacy and can effectively prevent the rebound of blood bilirubin.


e-Cigarette Use Among Youth in the United States, 2019.
The prevalence of e-cigarette use among US youth increased from 2011 to 2018. Continued monitoring of the prevalence of e-cigarette and other tobacco product use among youth is important to inform public health policy, planning, and regulatory efforts. To estimate the prevalence of e-cigarette use among US high school and middle school students in 2019 including frequency of use, brands used, and use of flavored products. Cross-sectional analyses of a school-based nationally representative sample of 19 018 US students in grades 6 to 12 participating in the 2019 National Youth Tobacco Survey. The survey was conducted from February 15, 2019, to May 24, 2019. Self-reported current (past 30-day) e-cigarette use estimates among high school and middle school students; frequent use (≥20 days in the past 30 days) and usual e-cigarette brand among current e-cigarette users; and use of flavored e-cigarettes and flavor types among current exclusive e-cigarette users (no use of other tobacco products) by school level and usual brand. Prevalence estimates were weighted to account for the complex sampling design. The survey included 10 097 high school students (mean [SD] age, 16.1 [3.0] years; 47.5% female) and 8837 middle school students (mean [SD] age, 12.7 [2.8] years; 48.7% female). The response rate was 66.3%. An estimated 27.5% (95% CI, 25.3%-29.7%) of high school students and 10.5% (95% CI, 9.4%-11.8%) of middle school students reported current e-cigarette use. Among current e-cigarette users, an estimated 34.2% (95% CI, 31.2%-37.3%) of high school students and 18.0% (95% CI, 15.2%-21.2%) of middle school students reported frequent use, and an estimated 63.6% (95% CI, 59.3%-67.8%) of high school students and 65.4% (95% CI, 60.6%-69.9%) of middle school students reported exclusive use of e-cigarettes. Among current e-cigarette users, an estimated 59.1% (95% CI, 54.8%-63.2%) of high school students and 54.1% (95% CI, 49.1%-59.0%) of middle school students reported JUUL as their usual e-cigarette brand in the past 30 days; among current e-cigarette users, 13.8% (95% CI, 12.0%-15.9%) of high school students and 16.8% (95% CI, 13.6%-20.7%) of middle school students reported not having a usual e-cigarette brand. Among current exclusive e-cigarette users, an estimated 72.2% (95% CI, 69.1%-75.1%) of high school students and 59.2% (95% CI, 54.8%-63.4%) of middle school students used flavored e-cigarettes, with fruit, menthol or mint, and candy, desserts, or other sweets being the most commonly reported flavors. In 2019, the prevalence of self-reported e-cigarette use was high among high school and middle school students, with many current e-cigarette users reporting frequent use and most of the exclusive e-cigarette users reporting use of flavored e-cigarettes.


[The primary diagnostic significance of the epworth sleepiness scale in patients with obstructive sleep apnea syndrome].
To evaluate the diagnostic usefulness of epworth sleepiness scale (ESS) in patients with OSAS. The questionnaire of the epworth sleepiness scale was used to evaluate 189 patients with OSAS and 42 patients with snoring. The results were compared to those of polysomnography. Significant differences in ESS-SP, AHI and sleep structure were found between patients with OSAS and patients with scoring. A significant correlation was found between ESS-SP score and AHI (r = 0.44, P < 0.01). The patients with OSAS had significantly higher scores than those without OSAS. The specificity of this method was 83% (snoring), 90% (mild OSAS), 79% (moderate OSAS) and 82% (severe OSAS). ESS-SP is consistent with clinical diagnosis and could be used as a primary diagnostic method in patients with OSAS, especially in primary-care hospitals.


Relationship between prostaglandins and cyclic-AMP in the process of implantation in rats.
The effect of alloxan, a known inhibitor of adenylate cyclase, on the levels of prostaglandins E and F was investigated in pregnant rats. Animals were treated intraluminally with alloxan in normal saline or alloxan plus cyclic-AMP in normal saline or normal saline alone on day 4 of pregnancy. The uteri were collected on days 5 and 6 of pregnancy and the prostaglandins E and F were extracted and measured by a radioimmunoassay technique. In the alloxan treated rats, a significant reduction in PGE and PGF levels was found on days 5 and 6 of pregnancy as compared to untreated control group, whereas in the alloxan plus cyclic-AMP treated group the levels of PGE and PGF were comparable to those of the untreated control group. These findings suggest a possible relationship between prostaglandins and cyclic-AMP in the process of implantation in rats.


Malignant melanoma of the choroid associated with spontaneous expulsive choroidal hemorrhage.
A 79-year-old man initially had a perforated corneal ulcer of his blind right eye. The next day a spontaneous expulsive choroidal hemorrhage occurred just before scheduled enucleation. Histopathologic examination of the enucleated eye revealed a severe necrosis of several posterior ciliary arteries in the expulsive choroidal hemorrhage, as well as a large occult spindle B malignant melanoma of the choroid. The necrosis of the posterior ciliary arteries may have been the cause of the choroidal hemorrhage. The finding of an occult malignant melanoma may be more than a chance occurrence of two unrelated events, inasmuch as both are associated with necrosis of the posterior ciliary arteries.


Structural basis for viral 5'-PPP-RNA recognition by human IFIT proteins.
Interferon-induced proteins with tetratricopeptide repeats (IFITs) are innate immune effector molecules that are thought to confer antiviral defence through disruption of protein-protein interactions in the host translation-initiation machinery. However, it was recently discovered that IFITs can directly recognize viral RNA bearing a 5'-triphosphate group (PPP-RNA), which is a molecular signature that distinguishes it from host RNA. Here we report crystal structures of human IFIT5, its complex with PPP-RNAs, and an amino-terminal fragment of IFIT1. The structures reveal a new helical domain that houses a positively charged cavity designed to specifically engage only single-stranded PPP-RNA, thus distinguishing it from the canonical cytosolic sensor of double-stranded viral PPP-RNA, retinoic acid-inducible gene I (RIG-I, also known as DDX58). Mutational analysis, proteolysis and gel-shift assays reveal that PPP-RNA is bound in a non-sequence-specific manner and requires a 5'-overhang of approximately three nucleotides. Abrogation of PPP-RNA binding in IFIT1 and IFIT5 was found to cause a defect in the antiviral response by human embryonic kidney cells. These results demonstrate the mechanism by which IFIT proteins selectively recognize viral RNA, and lend insight into their downstream effector function.


[Effect of the delta sleep peptide on epileptic activity in the cerebral cortex of rats and cats].
In free behaviour experiments on rats it has been shown that the intraperitoneal injection of delta sleep-inducing peptide (DSIP) (100 micrograms/kg) suppressed penicillin-induced relatively moderate epileptic foci which generated spike potentials as well as severe foci with ictal epileptic discharges. In the experiments on cats it was shown that intravenous DSIP injection (100 micrograms/kg) suppressed strychnine-induced epileptic focus and complexes of epileptic foci.


Multiple roles of HOX proteins in Metastasis: Let me count the ways.
Knowledge of the role of HOX proteins in cancer has been steadily accumulating in the last 25 years. They are encoded by 39 HOX genes arranged in 4 distinct clusters, and have unique and redundant function in all types of cancers. Many HOX genes behave as oncogenic transcriptional factors regulating multiple pathways that are critical to malignant progression in a variety of tumors. Some HOX proteins have dual roles that are tumor-site specific, displaying both oncogenic and tumor suppressor function. The focus of this review is on how HOX proteins contribute to growth or suppression of metastasis. The review will cover HOX protein function in the critical aspects of epithelial-mesenchymal transition, in cancer stem cell sustenance and in therapy resistance, manifested as distant metastasis. The emerging role of adiposity in both initiation and progression of metastasis is described. Defining the role of HOX genes in the metastatic process has identified candidates for targeted cancer therapies that may combat the metastatic process. We will discuss potential therapeutic opportunities, particularly in pathways influenced by HOX proteins.


Human immunodeficiency virus-related gastrointestinal pathology: a southern Africa perspective with review of the literature (part 1: infections).
Human immunodeficiency virus infection is rife in sub-Saharan Africa and in southern Africa in particular. Despite the increasing availability of antiretroviral therapy in this region, opportunistic infections remain common and frequently involve the gastrointestinal tract. To review the histopathologic findings and distinguishing features of human immunodeficiency virus-associated gastrointestinal infections in southern Africa and relate those findings to the documented international literature. The available literature on this topic was reviewed and supplemented with personal experience in a private histopathology practice in South Africa. In southern Africa, the range of gastrointestinal, opportunistic infectious pathology in human immunodeficiency virus afflicted patients is diverse and includes viral, bacterial, fungal, and parasitic infections. This infectious pathology is sometimes a manifestation of systemic disease. In profoundly immunocompromised patients, unusual histologic features, involvement of uncommon gastrointestinal tract sites, and more than one pathogen may be seen.


Insect antifeedant activity and hot taste for humans of selected natural and synthetic 1,4-dialdehydes.
The antifeedant activity towards larvae of Leptinotarsa decemlineata and Spodoptera littoralis and the hot taste for the human tongue have been determined for natural and synthetic 1,4-dialdehydes. Among the bicyclic dialdehydes the biological activity has been found to be dependent on the distance between the two aldehyde groups; tricyclic and pentacyclic dialdehydes are inactive in both tests. A short synthetic route to (-)- and (+)-polygodial is reported.


Lansoprazole for secondary prevention of gastric or duodenal ulcers associated with long-term non-steroidal anti-inflammatory drug (NSAID) therapy: results of a prospective, multicenter, double-blind, randomized, double-dummy, active-controlled trial.
Low-dose lansoprazole has not been intensively evaluated for its efficacy in the prevention of recurrent gastric or duodenal ulcers in patients receiving long-term non-steroidal anti-inflammatory drug (NSAID) therapy for pain relief in such diseases as rheumatoid arthritis, osteoarthritis, and low back pain. This multi-center, prospective, double-blind, randomized, active-controlled study involving 99 sites in Japan was designed to compare the efficacy of lansoprazole (15 mg daily) with gefarnate (50 mg twice daily). Patients with a history of gastric or duodenal ulcers who required long-term NSAID therapy were randomized to receive lansoprazole 15 mg daily (n = 185) or gefarnate 50 mg twice daily (n = 181) and followed up for 12 months or longer prospectively. The cumulative incidence of gastric or duodenal ulcer at days 91, 181, and 361 from the start of the study was calculated by the Kaplan-Meier method as 3.3, 5.9, and 12.7%, respectively, in the lansoprazole group versus 18.7, 28.5, and 36.9%, respectively, in the gefarnate group. The risk for ulcer development was significantly (log-rank test, P < 0.0001) lower in the lansoprazole group than in the gefarnate group, with the hazard ratio being 0.2510 (95% CI 0.1400-0.4499). A long-term follow-up study showed an acceptable safety profile for low-dose lansoprazole therapy, with diarrhea as the most frequent adverse event. Lansoprazole was superior to gefarnate in reducing the risk of gastric or duodenal ulcer recurrence in patients with a definite history of gastric or duodenal ulcers who required long-term NSAID therapy.


Interaction between municipal solid waste leachate and Bauru aquifer system: a study case in Brazil.
Leachate contamination is a chronic and urgent problem present in municipal solid waste (MSW) landfill. Geochemical mathematical models in this work was suitable to study the dynamics of the leachate from an MSW landfill located in the Midwest of Sao Paulo, Brazil, a region with high precipitation and temperature and rich in chalcophile compounds and lithophile compounds, despite contamination with nitrogenous compounds. After 13 years of local aquifer monitoring, some groundwater samplings in Feb. 2004, Aug. 2007, Nov. 2009, and Feb. 2014 were chosen to be simulated. The hydrolysis is the main process at the landfill, together with absorption, adsorption, complexation, dilution, cation exchange, and oxidation, besides nitrification, reoxidation, and reduction.


MiR-144-3p inhibits the proliferation and metastasis of lung cancer A549 cells via targeting HGF.
MicroRNAs have been confirmed as vital regulators in gene expression, which could affect multiple cancer cell biological behaviors. This study aims to elucidate the molecular mechanism of miR-144-3p in lung cancer cellular proliferation and metastasis. MiR-144-3p expression in lung cancer tissues and cell lines was detected by qRT-PCR. HGF was predicted as the target gene of miR-144-3p using TargetScan and dual luciferase reporter assay. Immunohistochemistry and qRT-PCR were used to explore the impacts of HCF on lung cancer tissues and cell lines. Impacts of miR-144-3p and HGF on cancer cellular proliferation, migration and invasion were elucidated by CCK-8, Flow cytometry, Transwell invasion and Wound-healing assay. Moreover, nude mouse xenograft model was established to evaluate the effects of miR-144-3p on lung cancer cells. MiR-144-3p exhibited a reduction in both lung cancer tissues and cell lines. HGF was a direct target of miR-144-3p. In contrast to the miR-144-3p expression level, HGF showed a higher level in lung cancer tissues and cell lines. Overexpression miR-144-3p suppressed A549 and NCI-H1299 cell proliferation and metastasis, whereas this was reversed by HGF. MiR-144-3p exhibited an inhibitory effect on A549 cell-induced tumor growth of nude mice. This study reveals miR-144-3p/HGF axis may be involved in the suppression of lung cancer cellular proliferation and development, and miR-144-3p may function as a potential therapeutic target in lung cancer treatment in the future.


Enhanced YB1/EphA2 axis signaling promotes acquired resistance to sunitinib and metastatic potential in renal cell carcinoma.
VHL mutations are the most common tumorigenic lesions in clear cell renal cell carcinoma (ccRCC) and result in continued activation of the HIF/VEGF pathway and uncontrolled cancer progression. Receptor tyrosine kinase (RTK) inhibitors such as sunitinib have been demonstrated to target tumorigenic signaling pathways, delay tumor progression, and improve patient prognosis in metastatic renal cell carcinoma (mRCC). Although several mechanisms of sunitinib resistance have been reported, the solutions to overcome this resistance remain unclear. In our study, we found that increased expression of Y-box binding protein 1 (YB1, a multidrug resistance associated protein) and EphA2 (a member of the erythropoietin-producing hepatocellular (Eph) receptor family, belonging to the RTK family) mediated sunitinib resistance and mRCC exhibited a large phenotypic dependence on YB1 and EphA2. In addition, our findings confirm that YB1 promotes the invasion, metastasis and sunitinib resistance of ccRCC by regulating the EphA2 signaling pathway. Furthermore, pharmacological inhibition of EphA2 through the small molecule inhibitor ALW-II-41-27 reduced the proliferation of sunitinib-resistant tumor cells, suppressed tumor growth in vivo, and restored the sensitivity of sunitinib-resistant tumor cells to sunitinib in vitro and in vivo. Mechanistically, YB1 increases the protein levels of EphA2 by maintaining the protein stability of EphA2 through inhibition of the proteasomal degradation pathway. Collectively, our findings provide the theoretical rationale that ccRCC metastasis and RTK-directed therapeutic resistance could be prospectively and purposefully targeted.


Drugs affecting the cholinergic system in the intact mammalian eye. I. Evaluation of the miotic activity of acetylcholine-like drugs in the mouse eye.
The effect of concentration and pH on the miotic activity of five acetylcholine-like drugs were studied in the intact mouse eye. The data suggests that it is mainly the nonionized form of the drug which contributes to its miotic activity. Acetylcholine-like drugs, degradable by cholinesterases, exert their miotic activity at higher concentrations than do those which are resistant to enzymatic hydrolysis. More active acetylcholine-like drugs appear to be less sensitive to concentration changes.


Drinking practices and cognitive functioning.
The relationships between drinking practices and cognitive functioning were examined in a non-patient sample. Neither the amount of alcohol consumed over a lifetime nor current frequency of drinking occasions was significantly (ps greater than .05) correlated with cognitive test scores. However, the quantity of alcohol consumed per drinking occasion was inversely related to performance on tests of abstraction, adaptive abilities and concept formation. The results suggest that social drinking may have deleterious effects on cognitive processes.


Harmful chemicals of heat not burn product and its induced oxidative stress of macrophages at air-liquid interface: Comparison with ultra-light cigarette.
Harmful and potential harmful chemicals (HPHCs) and oxidative stress of macrophages are major factors responsible for smoking-caused chronic respiratory diseases. However, comparisons of HPHCs among heat not burn (HnB) product and ultra-light cigarette and their induced oxidative stress of macrophages have not been investigated. The study detected HPHCs deliveries from HnB and ultra-light and measured their induced oxidative stress of macrophages cultured at air-liquid interface (ALI). Total particulate matter, tar and 28 chemicals delivered from HnB, ultra-light and 3R4F cigarettes were determined. Mouse mononuclear macrophages at ALI were exposed to the aerosol of three tobacco products. Cell viability was measured by MTT assay. Reduced glutathione was detected by colorimetry method. Reactive oxygen species (ROS) was determined by fluorescence method. The results showed levels of 26 common HPHCs from both HnB product and ultra-light cigarette were less than that from 3R4F cigarette. HnB product delivered formaldehyde, acetaldehyde, propanal, butyraldehyde and crotonaldehyde more than ultra-light cigarette. The levels of 21 HPHCs were lower in the HnB product compared to the ultra-light cigarette. At the same exposure dose and time, the order of cell viability induced by aerosol of that was HnB > ultra-light > 3R4F, the order of content of intracellular reduced glutathione induced by aerosol of that was HnB > ultra-light > 3R4F. It showed no significant difference of ROS level between ultra-light and HnB in each designed exposure dose. HnB induced more ROS than ultra-light cigarette in each designed exposure time. Conclusively, most HPHCs from HnB were lower than that from ultra-light, while certain harmful chemicals were higher than ultra-light, e.g., carbonyl compounds. HnB-induced oxidative stress of macrophages is less than ultra-light cigarette.


Oral delivery of bacteria: Basic principles and biomedical applications.
Bacterial therapy, which presents a smart platform for delivering and producing therapeutic agents, as monotherapy or in combination with other therapeutic modes, has provided a breakthrough for the treatment of a range of diseases. The integration of synthetic biology technology with bacteria enables their characteristics like chemotaxis and biomolecule secretion to outperform conventional diagnostics and therapeutics, thereby facilitating their clinical applications in a range of diseases. Compared to injection-administered bacteria, orally-delivered bacteria improve patient compliance while avoiding the risk of systemic infections. However, oral administration of microbes always leads to a substantial loss of viability due to the highly acidic environment in the stomach and bile salt in the intestine. Thus, the formulation of these bacteria into microcapsules using appropriate biomaterials is a promising approach for reducing cell death during gastrointestinal passage and controlling the release of these therapeutic cells across the intestinal tract. In this review, we reveal the basic principles of oral bacterial delivery, from internal genetic engineering approaches to external encapsulation and modification, and summarize the most recent biomedical applications. Finally, we discuss future trends in oral bacterial therapy as well as current challenges that need to be resolved to advance their clinical applications.


Pilon fractures: A new classification system based on CT-scan.
Actually, pilon fractures are classified according to AO and Ruedi Allgower classification systems based on X-rays. These classifications are less reproducible and do not provide necessary information for proper surgical planning. Aim of the study is to (1) propose a new classification system based on CT scan; (2) to check the prognostic value of this classification and (3) to evaluate its reliability and (4) reproducibility. We retrospectively reviewed 71 cases of pilon fracture. All fractures were classified according to AO, Ruedi Allgower and new proposed classification system by 5 surgeons. Clinical and radiographic evaluation were performed at a mean follow-up of 36 months. Cohen's K value was calculated in order to evaluate the interobserver and intraobserver agreement. Sixty-four of 71 fractures healed. Average AOFAS score was 91,7±7,8 in the Type I of new classification proposed, 87,7±7,8 in the Type II, 82±18,6 in type III, and 67,2±20,9 in type IV. Using the AO classification system the average K weighted value among the five reviewers was 0,51; using Ruedi Allgower classification it was 0,50 and using the new classification system it was 0,88 (p<0.0005). This study demonstrated that the new classification system is prognostic, reliable and reproducible. Moreover it provides a new treatment-oriented classification for this challenging fracture which affect the quality of life of the patients more than chronic diseases like diabetes and coronaropathy or pelvic fractures.


Adjuvant Therapy for High-Risk Melanoma: An In-Depth Examination of the State of the Field.
The consideration of systemic adjuvant therapy is recommended for patients with stage IIB-IV melanoma who have undergone surgical resection due to a heightened risk of experiencing melanoma relapse and mortality from melanoma. Adjuvant therapy options tested over the past three decades include high-dose interferon-α, immune checkpoint inhibitors (pembrolizumab, nivolumab), targeted therapy (dabrafenib-trametinib for BRAF mutant melanoma), radiotherapy and chemotherapy. Most of these therapies have been demonstrated to enhance relapse-free survival (RFS) but with limited to no impact on overall survival (OS), as reported in randomized trials. In contemporary clinical practice, the adjuvant treatment approach for surgically resected stage III-IV melanoma has undergone a notable shift towards the utilization of nivolumab, pembrolizumab, and BRAF-MEK inhibitors, such as dabrafenib plus trametinib (specifically for BRAF mutant melanoma) due to the significant enhancements in RFS observed with these treatments. Pembrolizumab has obtained regulatory approval in the United States to treat resected stage IIB-IIC melanoma, while nivolumab is currently under review for the same indication. This review comprehensively analyzes completed phase III adjuvant therapy trials in adjuvant therapy. Additionally, it provides a summary of ongoing trials and an overview of the main challenges and future directions with adjuvant therapy.


Is DNA repair controlled by a biological logic circuit?
The possible utilization of biological logic circuit(s) in the integration and regulation of DNA repair is discussed. The author believes this mode of regulation likely applies to many other areas of cell biology; however, there are currently more experimental data to support its involvement in the control of DNA repair. Sequential logic processes always require a clock to orchestrate the orderly processing of events. In the proposed hypothesis, the pulses in the expression of p53 serve this function. Given the many advantages of logic type control, one would expect that in the course of ~ 3 billion years of evolution, where single cell life forms were likely the only forms of life, a biological logic type control system would have evolved to control at least some biological processes. Several other required components in addition to the 'clock' have been identified, such as; a method to temporarily inactivate repair processes when they are not required (e.g. the reversible inactivation of MGMT, a suicide repair protein, by phosphorylation); this prevents complex DNA repair systems with potentially overlapping repair functions from interfering with each other.


Reduction in Diabetes-Related Major Amputation Rates After Implementation of a Multidisciplinary Model: An Evaluation in Alberta, Canada.
Diabetes-related lower limb amputations (LLAs) are a major complication that can be reduced by employing multidisciplinary center frameworks such as the Toe and Flow model (TFM). In this study, we investigate the LLAs reduction efficacy of the TFM compared to the standard of care (SOC) in the Canadian health-care system. We retrospectively reviewed the anonymized diabetes-related LLA reports (2007-2017) in Calgary and Edmonton metropolitan health zones in Alberta, Canada. Both zones have the same provincial health-care coverage and similar demographics; however, Calgary operates based on the TFM while Edmonton with the provincial SOC. LLAs were divided into minor and major amputation cohorts and evaluated using the chi-square test, linear regression. A lower major LLAs rate was denoted as a sign for higher efficacy of the system. Although LLAs numbers remained relatively comparable (Calgary: 2238 and Edmonton: 2410), the Calgary zone had both significantly lower major (45%) and higher minor (42%) amputation incidence rates compared to the Edmonton zone. The increasing trend in minor LLAs and decreasing major LLAs in the Calgary zone were negatively and significantly correlated (r = -0.730, p = 0.011), with no significant correlation in the Edmonton zone. Calgary's decreasing diabetes-related major LLAs and negative correlation in the minor-major LLAs rates compared to its sister zone Edmonton, provides support for the positive impact of the TFM. This investigation includes support for a modernization of the diabetes-related limb preservation practice in Canada by implementing TFMs across the country to combat major LLAs.


A case of Graves' disease associated with autoimmune haemolytic anaemia.
This report describes simultaneous autoimmune thyrotoxicosis and autoimmune haemolytic anaemia. Autoimmune haematological abnormalities should be excluded in patients with Graves' disease and thyroid function and thyroid antibody status should be evaluated in patients with autoimmune haemolytic anaemia.


Regulation of autophagy in human skeletal muscle: effects of exercise, exercise training and insulin stimulation.
Regulation of autophagy in human muscle in many aspects differs from the majority of previous reports based on studies in cell systems and rodent muscle. An acute bout of exercise and insulin stimulation reduce human muscle autophagosome content. An acute bout of exercise regulates autophagy by a local contraction-induced mechanism. Exercise training increases the capacity for formation of autophagosomes in human muscle. AMPK activation during exercise seems insufficient to regulate autophagosome content in muscle, while mTORC1 signalling via ULK1 probably mediates the autophagy-inhibiting effect of insulin. Studies in rodent muscle suggest that autophagy is regulated by acute exercise, exercise training and insulin stimulation. However, little is known about the regulation of autophagy in human skeletal muscle. Here we investigate the autophagic response to acute one-legged exercise, one-legged exercise training and subsequent insulin stimulation in exercised and non-exercised human muscle. Acute one-legged exercise decreased (P<0.01) lipidation of microtubule-associated protein 1A/1B-light chain 3 (LC3) (∼ 50%) and the LC3-II/LC3-I ratio (∼ 60%) indicating that content of autophagosomes decreases with exercise in human muscle. The decrease in LC3-II/LC3-I ratio did not correlate with activation of 5'AMP activated protein kinase (AMPK) trimer complexes in human muscle. Consistently, pharmacological AMPK activation with 5-aminoimidazole-4-carboxamide riboside (AICAR) in mouse muscle did not affect the LC3-II/LC3-I ratio. Four hours after exercise, insulin further reduced (P<0.01) the LC3-II/LC3-I ratio (∼ 80%) in muscle of the exercised and non-exercised leg in humans. This coincided with increased Ser-757 phosphorylation of Unc51 like kinase 1 (ULK1), which is suggested as a mammalian target of rapamycin complex 1 (mTORC1) target. Accordingly, inhibition of mTOR signalling in mouse muscle prevented the ability of insulin to reduce the LC3-II/LC3-I ratio. In response to 3 weeks of one-legged exercise training, the LC3-II/LC3-I ratio decreased (P<0.05) in both trained and untrained muscle and this change was largely driven by an increase in LC3-I content. Taken together, acute exercise and insulin stimulation reduce muscle autophagosome content, while exercise training may increase the capacity for formation of autophagosomes in muscle. Moreover, AMPK activation during exercise may not be sufficient to regulate autophagy in muscle, while mTORC1 signalling via ULK1 probably mediates the autophagy-inhibiting effect of insulin.


Operability of atrial septal defect with borderline pulmonary vascular resistance index: A study in developing country.
Pulmonary arterial hypertension secondary to atrial septal defect (ASD) is an important determinant of morbidity and mortality in defect closure. We aimed to compare perioperative outcome between preoperative borderline and low pulmonary vascular resistance index (≥4 WU.m2 and <4 WU.m2, respectively) in surgical closure of secundum atrial septal defect with concomitant pulmonary arterial hypertension. This was a single-center retrospective cohort study between January 2015 and January 2020. We classified patients with low and borderline PVRI who underwent ASD closure and recorded the perioperative outcomes. We analyzed a total of 183 patients with atrial septal defect and pulmonary arterial hypertension; 92 patients with borderline PVRI and 91 patients with low PVRI. Borderline pulmonary vascular resistance index was not associated with increased risk of postoperative mortality (p = 0.621; OR0.48, 95% CI 0.04-5.48), but associated with higher risk of overall morbidity in bivariate analysis (p = 0.002; OR3.28, 95% CI 1.5-6.72). Multivariate analysis showed positive association of borderline pulmonary vascular resistance index (p = 0.045; OR2.63, 95% CI 1.02-6.77) and preoperative tricuspid valve gradient ≥64 mmHg (p = 0.034; OR2.77, 95% CI 1.08-7.13) with overall morbidity. There is no difference in incidence of in-hospital mortality between preoperative borderline and low pulmonary vascular resistance index patients. However, preoperative borderline pulmonary vascular resistance index and tricuspid valve gradient ≥64 mmHg are associated with increased overall morbidity after surgical closure in secundum atrial septal defect patients with pulmonary arterial hypertension.


Respiratory failure and lethal hypotension due to blue-ringed octopus and tetrodotoxin envenomation observed and counteracted in animal models.
The effects of crude blue-ringed octopus venom gland extract and tetrodotoxin (TTX) on anaesthetised rats and rabbits were studied. Paralysis of the respiratory musculature causing anoxia and cyanosis was overcome with positive, artificial respiration. The second lethal mechanism of the toxins: rapid and severe hypotension, had to be counteracted peripherally, since neural transmission had been drastically reduced by the toxins. Noradrenaline, d-amphetamine, phenylephrine and methoxamine, agonists acting on vascular adrenergic a-receptors, were tested.


The immune system in traumatic brain injury.
Traumatic brain injury (TBI) is the major cause of death in children and young adults and one of the major reasons for long-term disability worldwide, however, no specific clinical treatment option could be established so far. This is surprising since it is well known that following the initial mechanical damage to the brain a plethora of delayed processes are activated which ultimately result in additional brain damage. Among these secondary mechanisms, acute and chronic activation of the innate and adaptive immune system is increasingly believed to play an important role for the pathogenesis of TBI. Understanding these processes may results in new, clinically applicable therapeutic options for TBI patients.


Treatment in combined medical psychiatry units: an integrative model.
Approximately 14 medical psychiatry units have opened over the last 15 years due to the recognition of the frequent concurrence of medical and psychiatric illnesses. This article discusses the clinical problems encountered when medical care and psychiatric care are integrated and their impact on medical and nursing staff. Group therapy programs on medical psychiatry units may enhance psychiatric treatment and help maintain a psychiatric focus by both patients and staff, despite the patients' significant medical problems. Medical psychiatric units must adopt an integrative model of care that includes all disciplines involved on the units if they are to meet their goal of providing effective medical and psychiatric care.


Cultivation and functional characterization of 79 planctomycetes uncovers their unique biology.
When it comes to the discovery and analysis of yet uncharted bacterial traits, pure cultures are essential as only these allow detailed morphological and physiological characterization as well as genetic manipulation. However, microbiologists are struggling to isolate and maintain the majority of bacterial strains, as mimicking their native environmental niches adequately can be a challenging task. Here, we report the diversity-driven cultivation, characterization and genome sequencing of 79 bacterial strains from all major taxonomic clades of the conspicuous bacterial phylum Planctomycetes. The samples were derived from different aquatic environments but close relatives could be isolated from geographically distinct regions and structurally diverse habitats, implying that 'everything is everywhere'. With the discovery of lateral budding in 'Kolteria novifilia' and the capability of the members of the Saltatorellus clade to divide by binary fission as well as budding, we identified previously unknown modes of bacterial cell division. Alongside unobserved aspects of cell signalling and small-molecule production, our findings demonstrate that exploration beyond the well-established model organisms has the potential to increase our knowledge of bacterial diversity. We illustrate how 'microbial dark matter' can be accessed by cultivation techniques, expanding the organismic background for small-molecule research and drug-target detection.


Biochar: A review of its impact on pesticide behavior in soil environments and its potential applications.
Biochar is produced from the pyrolysis of carbon-rich plant- and animal-residues under low oxygen and high temperature conditions and has been increasingly used for its positive role in soil compartmentalization through activities such as carbon sequestration and improving soil quality. Biochar is also considered a unique adsorbent due to its high specific surface area and highly carbonaceous nature. Therefore, soil amendments with small amounts of biochar could result in higher adsorption and, consequently, decrease the bioavailability of contaminants to microbial communities, plants, earthworms, and other organisms in the soil. However, the mechanisms affecting the environmental fate and behavior of organic contaminants, especially pesticides in biochar-amended soil, are not well understood. The purpose of this work is to review the role of biochar in primary processes, such as adsorption-desorption and leaching of pesticides. Biochar has demonstrable effects on the fate and effects of pesticides and has been shown to affect the degradation and bioavailability of pesticides for living organisms. Moreover, some key aspects of agricultural and environmental applications of biochar are highlighted.


Hip dysplasia in the New Zealand Huntaway and Heading dog.
To conduct a practice-based survey to obtain, for the first time, data on hip dysplasia in the New Zealand working dog breeds of Huntaway and Heading Dogs. A mailed request and personal approaches to farmer clients of Taihape and Waimarino Veterinary Services were used to recruit dog owners from the Taihape district in the North Island of New Zealand. Recruited dogs were radiographed under anaesthesia in a standard position with both hind limbs extended so that the femurs were parallel and rotated medially. The standard scoring system adopted by the New Zealand Veterinary Association (NZVA) Hip Dysplasia Scheme was used to score the hip radiographs of the dogs. Radiographs of the hips of 141 dogs (93 Huntaways; 48 Heading Dogs), were evaluated. The overall prevalence of hip dysplasia (defined as a combined score from both hips of 10) was 17.7%. Prevalences in Huntaways and Heading Dogs were 23.6% and 6.3%, respectively; in this sample of dogs, the odds ratio (and 95% confidence interval) for Huntaways having a score of 10 was 4.6 (1.316.0) that of Heading Dogs. The average scores were 10.8 for Huntaways and 5.9 for Heading Dogs. Huntaways were at the higher end of the breed average scores for dogs recorded in the NZVA Hip Dysplasia Scheme and Heading Dogs at the lower end. This preliminary study indicates that hip dysplasia may be a problem in the Huntaway breed. Investigation of the epidemiology of the condition in this breed is warranted and consideration should be given to removing high-risk Huntaways from the breeding pool.


Peripheral nerve repair using a poly(organo)phosphazene tubular prosthesis.
Nerve regeneration experiments were carried out using tubular nerve guides of poly[(ethylalanato)1.4(imidazolyl)0.6phosphazene] (PEIP). By means of in vivo tests, this polymer was found to be biodegradable and transformed into harmless products. The tubular nerve guides were prepared by deposition of the dissolved polymer on a glass capillary tube, followed by evaporation of the solvent (methylene dichloride). After transectioning, rat sciatic nerve stumps were immediately sutured into the ends of 10-mm-long polymer tubes. On removal of the prosthesis, after implantation for 45 d, a tissue cable was found bridging the nerve stumps in all cases. Histological analysis revealed that the tissue cable was essentially composed of a regenerated nerve fibre bundle. A parallel series of experiments was undertaken to compare the use of silicone tubes that are not biodegradable and are most frequently used for studies of nerve regeneration with tubulization techniques. The advantages of biodegradable PEIP tubular nerve guides used for peripheral nerve repair are discussed.


Genome-wide association study for four measures of epigenetic age acceleration and two epigenetic surrogate markers using DNA methylation data from Taiwan Biobank.
To highlight the genetic architecture for epigenetic aging, McCartney et al. recently identified 137 significant single-nucleotide polymorphisms based on genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and two epigenetic surrogate markers. However, none Asian ancestry studies have been included in this or previous meta-analyses. I performed a GWAS on blood DNA methylation (DNAm) levels of 2309 Taiwan Biobank (TWB) participants. Owing to the fact that the sample size of an individual GWAS of DNAm data is still not large, I adopted the 'prioritized subset analysis' (PSA) method to boost the power of a GWAS. The four epigenetic clocks and the two epigenetic surrogate markers were investigated, respectively. I replicated 21 out of the 137 aging-associated genetic loci by applying the PSA method to the TWB DNAm data. Moreover, I identified five novel loci, including rs117530284 that was associated with the 'epigenetic age acceleration' (EAA) according to Lu et al.'s GrimAge (called 'GrimEAA'). Considering 16 covariates (sex, BMI, smoking status, drinking status, regular exercise, educational attainment and the first 10 ancestry principal components), each 'A' allele of rs117530284 in the IBA57 gene was found to be associated with a 1.5943-year GrimEAA (95% confidence interval = [1.0748, 2.1138]). IBA57 is a protein coding gene and is associated with multiple mitochondrial dysfunctions syndromes. A decline in mitochondrial activity and quality is associated with aging and many age-related diseases. This is one of the first DNAm GWAS for individuals of Asian ancestry.


Principal determinants of the length of remission of psoriasis vulgaris after topical, NB-UVB, and PUVA therapy: a follow-up study.
Periods of remission and of exacerbation of psoriatic lesions are common in psoriasis. We recently reported C-reactive protein (CRP) as a marker of psoriasis severity and that some patients still presented with a residual inflammation after treatment. We wondered if this residual inflammation could underlie an earlier exacerbation of psoriasis. The purpose of our study was to evaluate if there is a relationship between CRP levels, Psoriasis Area and Severity Index (PASI), and body mass index (BMI), at the end of psoriasis treatment, with the length of psoriasis remission. We followed 46 patients studied at the end of treatment, to record the length of remission; 9 of the patients were treated with topical agents, 17 with narrow-band UVB (NB-UVB), and 20 with psoralen plus UVA (PUVA). We found that the length of remission correlated with the values for PASI and CRP at the end of therapy. By performing a multiple linear regression analysis, CRP, PASI, and BMI were each significantly associated with length of remission. Patients with residual inflammation at the end of treatment presented with a significantly shorter length of remission. When considering patients grouped according to the used therapies, CRP and PASI also emerged as potential determinants of length of remission, especially in the case of patients treated with NB-UVB and topical therapy. Our data suggest that CRP and PASI are important determinants of length of psoriasis remission for patients treated with phototherapy or topical therapy. Further studies with larger groups of patients are warranted to test this hypothesis. Moreover, we propose that, by the end of the treatment, the evaluation of CRP and PASI could be important to decide, when possible, if the treatment should be continued to achieve lower CRP values and longer periods of remission.


Functional recovery of chronic complete idiopathic transverse myelitis after administration of neurotrophic factors.
Case report. To evaluate the functional recovery of chronic complete idiopathic transverse myelitis (ITM) after administration of acidic fibroblast growth factor (aFGF). A 28-year-old woman presented with a 4-year history of spastic paralysis, sensory level at T10, urinary retention and constipation due to ITM. In all, 20 microg aFGF bolus injection was applied via intradural lumbar puncture, which was repeated every 5 months for 15 months. At 3 weeks after first injection, the patient experienced vague sensation at approximately T12-L1 dermatomes. At 2 months after the second injection, muscle activities and gait pattern were recorded in bilateral gluteus and hip abductors as she ambulated with long leg brace and axillary crutches. Increased walking speeds, reduced pelvic tilting and reduced compensatory trunk rotation during the swing phase were also demonstrated as compared to the initial gait analysis. At 18 months after injection, motor evoked potentials were obtained in hip abductors of both legs. aFGF may increase the efficacy of spinal reactivation/regeneration and is a potential remedy for chronic transverse myelitis.


Relationship between sleep disorders and other non-motor symptoms in Parkinson's disease.
The association between sleep disorders and other non-motor symptoms (NMS) in Parkinson's disease (PD) has been scarcely investigated. To describe the prevalence of insomnia and hypersomnia in PD and analyze their relationship with other NMS. Cross-sectional, multicenter study including 388 PD patients evaluated with Hoehn and Yahr, Clinical Impression of Severity Index for PD, Scales for Outcomes in Parkinson's Disease (SCOPA)-Sleep(S), SCOPA-Cognition, SCOPA-Psychiatric Complications, SCOPA-Autonomic, Hospital Anxiety and Depression Scale, and fatigue and pain visual analogue scales. Spearman correlation coefficients, Mann-Whitney test and multiple linear regression analysis were applied. Mean age (54% male) was 65.9 ± 11.2 years old, with disease duration of 8.1 ± 6.0 years and median HY = 2 (range: 1-5). Mean SCOPA-S nocturnal sleep (NS) was 5.4 ± 4.0 (range: 0-15), daytime sleepiness (DS) was 3.76 ± 3.04 (range: 0-15). Most of the sample declared nocturnal or daytime sleep problems (87.4%). Weak-to-moderate correlations were found between sleep disturbances and other NMS (range: 0.14-0.37). SCOPA-S subscales showed higher scores with the presence of most other NMS such as psychiatric complications and autonomic dysfunctions (p < 0.05). Regression models showed that fatigue, depression, urinary, cardiovascular, and thermoregulatory dysfunctions were significant determinants of SCOPA-NS score (variance: 23%); cognitive impairment, urinary, cardiovascular, and pupillomotor disorders influenced SCOPA-DS score (variance: 14%). Insomnia and daytime sleepiness are extremely prevalent in PD. Depression, fatigue, cognitive impairment, cardiovascular, urinary and thermoregulatory dysfunctions may contribute to insomnia/hypersomnia. This is the first clinical study to relate cardiovascular and thermoregulatory dysfunctions with sleep in PD.


Combined DNA Damage Repair Interference and Ion Beam Therapy: Development, Benchmark, and Clinical Implications of a Mechanistic Biological Model.
Our purpose was to develop a mechanistic model that describes and predicts radiation response after combined DNA damage repair interference (DDRi) and particle radiation therapy. The heterogeneous dose distributions of protons and 4He ions were implemented into the "UNIfied and VERSatile bio-response Engine" (UNIVERSE). Predictions for monoenergetic and mixed fields over clinically relevant dose and linear energy transfer range were compared with experimental in vitro survival data measured in this work as well as data available in the literature, including different cell lines and DDR interferences. Ultimately, UNIVERSE predictions were investigated in a patient plan. UNIVERSE accurately predicts survival of cell lines with and without DDRi in clinical settings of ion beam therapy based only on 3 parameters derived from photon data. With increasing dose or linear energy transfer, the radiosensitizing effect of DDRi decreases, resulting in diminished relative biological effect of ion beam radiation for cells subjected to DDRi in comparison to cells that are not. Similar trends were observed in patient plan recalculations; however, this analysis also suggests that DDRi + particle radiation therapy may better preserve the therapeutic window in comparison to DDRi + photon radiation therapy. The presented framework represents the first mechanistic model of combined DDRi and particle radiation therapy comprehensively benchmarked in clinically relevant scenarios and a step toward more personalized treatment. It reveals potential differences between DDRi + photon radiation therapy versus DDRi + particle radiation therapy, which have not been described so far. UNIVERSE could aid in appraising the clinical viability of combined administration of radiosensitizing drugs and charged particle therapy, as well as the identification of patients with known DDR deficiencies in the tumor who might benefit from therapy with light ions, freeing limited space at heavy ion therapy centers.


SEM and chemical micro-analysis in a failed total knee prosthesis.
Authors performed SEM and EDS analyses in a cemented removed knee prosthesis demonstrating the average values of mineral elements in the bone surrounding the prosthesis. The composition of the metallic prosthesis surface in different microareas was also studied.


Bancroftian filariasis in coastal north Trinidad: the effects of mass chemotherapy using spaced doses of diethylcarbamazine citrate on human microfilaraemias and vector infection rates.
The effects of a mass chemotherapy programme using spaced doses of diethylcarbamazine citrate on Wuchereria bancrofti microfilaraemias and vector infection rates were studied in an isolated rural community of 650 people in north Trinidad where a microfilaria rate of 15% had previously been recorded. A single oral dose of 6 mg/kg body weight was given at monthly intervals for one year. After 6 months, 79% (52/66) of persons previously microfilaraemic had become negative. After 12 months the negative proportion had increased to 90% (63/70). The geometric mean microfilaria density of those still microfilaraemic was reduced from 19.7 to 4.6 per 100 mm3 of blood. Of 147 initially negative persons, none had become positive following treatment. Filarial infection rates in Culex quinquefasciatus from randomly sampled houses fell from 6.4% to zero; in houses where occupants with microfilaraemia had been identified before treatment, the rate was reduced from 15.8% to zero. In a supplementary study, however, weekly collections from one initially positive house showed a rapid decline in the vector infection rate from 43% to 2% after three months but an additional 3 months elapsed before the index reached zero. There was negligible microfilarial uptake by the vectors from residual low-density microfilaraemias (less than 10 microfilariae per 100 mm3 of blood) after chemotherapy.


[Pharmacological treatment of delirium in palliative care patients. A systematic literature review].
This systematic literature review aims to collect and analyse relevant clinical trials for the drug treatment of delirium in palliative care. The search was conducted including July 2012 in Medline (from 1966) and Embase (from 1974). The search retrieved 448 studies, of which 3 studies could be included in the analysis. Treatment with the antipsychotic drug haloperidol can be recommended, which is also true to a somewhat lower extent for the antipsychotics olanzapine and aripiprazole. Treatment with lorazepam only should be avoided. This literature analysis reflects the positive clinical experience, especially when using haloperidol. To confirm these recommendations, further substantial clinical studies are needed.The English full-text version of this article can be found at SpringerLink (under "Supplemental").


Maximum Value Measured by 2-D Shear Wave Elastography Helps in Differentiating Malignancy from Benign Focal Liver Lesions.
The goal of the work described here was to evaluate the diagnostic efficacy of 2-D shear wave elastography (2-D SWE) in differentiating malignancy from benign focal liver lesions (FLLs). The maxima, minima, means and the standard deviations of 2-D SWE measurements, expressed in kilopascals (Emax, Emin, Emean, ESD), were obtained for 221 patients with 229 FLLs. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic performance of 2-D SWE. The Mann-Whitney U-test was used to assess inter-group differences. Emax, Emin, Emean and ESD were significantly higher in the 164 malignant lesions than in the 65 benign lesions (p < 0.001). For identification of malignant FLLs, the areas under receiver operating characteristic curves for Emax, Emin, Emean and ESD were 0.920, 0.710, 0.879 and 0.915, respectively. Emax was 96.21 ± 35.40 for 19 intrahepatic cholangiocarcinomas and 90.32 ± 54.71 for 35 liver metastatic lesions, which were significantly higher than 61.83 ± 28.87 for 103 hepatocellular carcinomas (p < 0.0001 and p = 0.0237). Emax was 38.72 ± 18.65 for 15 focal nodular hyperplasias, which was significantly higher than 20.56 ± 10.74 for 37 hemangiomas (p = 0.0009). The Emax values for adjacent liver parenchyma of hepatocellular carcinomas and intrahepatic cholangiocarcinomas were significantly higher than those for the other three lesion types (p < 0.005). In conclusion, Emax values of FLLs and adjacent liver parenchyma could help in differentiating malignant from benign FLLs.