Bath salts in the emergency department: a survey of emergency clinicians' experience with bath salts-intoxicated patients.
Several novel synthetic amphetamines have been marketed worldwide as "bath salts." The use of bath salts is associated with severe medical consequences resulting in a US federal ban over the last 3 years on the more common substances found in this group. Bath salts intoxication has a relatively nonspecific presentation, and urine toxicology confirmation in emergency departments (EDs) is impractical because the turnaround time is several days. Emergency clinicians must therefore rely heavily on patients' self-reports to verify the diagnosis. We performed an online survey of emergency clinicians to determine their degree of exposure to bath salts-intoxicated patients, the clinically relevant features of such patients, and the typical emergency management. We invited 124 physicians and physician assistants in 7 Cleveland Clinic EDs to participate in an online survey. From a total of 43 of the 124 respondents, 77% did not specifically ask patients about bath salts use. Sixty percent had encountered a bath salts-intoxicated individual. Most respondents reported that the majority of patients were male, were between 19 and 29 years old, and used other drugs in addition to bath salts. Agitation, aggression/violence, and hallucinations were reported to be the most common presentations, and intravenous/intramuscular tranquilization was reported as the most often used management. Most patients were discharged home from the ED. Despite the lack of toxicology screening in EDs, about two thirds of the surveyed emergency clinicians encountered bath salts-intoxicated individuals. Our study demonstrates the need for increased screening of bath salts intoxication in EDs, especially in agitated patients.


Cognitive-behavioral psychotherapy for anxiety and depressive disorders in children and adolescents: an evidence-based medicine review.
To review the literature on the cognitive-behavioral treatment of children and adolescents with anxiety and depressive disorders within the conceptual framework of evidence-based medicine. The psychiatric and psychological literature was systematically searched for controlled trials applying cognitive-behavioral treatment to pediatric anxiety and depressive disorders. For both anxiety and depression, substantial evidence supports the efficacy of problem-specific cognitive-behavioral interventions. Comparisons with wait-list, inactive control, and active control conditions suggest medium to large effects for symptom reduction in primary outcome domains. From an evidence-based perspective, cognitive-behavioral therapy is currently the treatment of choice for anxiety and depressive disorders in children and adolescents. Future research in this area will need to focus on comparing cognitive-behavioral psychotherapy with other treatments, component analyses, and the application of exportable protocol-driven treatments to divergent settings and patient populations.


Smaller species but larger stages: Warming effects on inter- and intraspecific community size structure.
Global warming can alter size distributions of animal communities, but the contribution of size shifts within versus between species to such changes remains unknown. In particular, it is unclear if expected body size shrinkage in response to warming, observed at the interspecific level, can be used to infer similar size shifts within species. In this study, we compare warming effects on interspecific (relative species abundance) versus intraspecific (relative stage abundance) size structure of competing consumers by analyzing stage-structured bioenergetic food web models consisting of one or two consumer species and two resources, parameterized for pelagic plankton. Varying composition and temperature and body size dependencies in these models, we predicted interspecific versus intraspecific size structure across temperature. We found that warming shifted community size structure toward dominance of smaller species, in line with empirical evidence summarized in our review of 136 literature studies. However, this result emerged only given a size-temperature interaction favoring small over large individuals in warm environments. In contrast, the same mechanism caused an intraspecific shift toward dominance of larger (adult) stages, reconciling disparate observations of size responses within and across zooplankton species in the literature. As the empirical evidence for warming-driven stage shifts is scarce and equivocal, we call for more experimental studies on intraspecific size changes with warming. Understanding the global warming impacts on animal communities requires that we consider and quantify the relative importance of mechanisms concurrently shaping size distributions within and among species.


Draft Genome Sequence of Blood Disease Bacterium A2 HR-MARDI, a Pathogen Causing Banana Bacterial Wilt.
Blood disease bacterium A2 HR-MARDI was isolated from banana plants infected with banana blood disease and which were planted in Kuala Kangsar, Malaysia. Here, we report a draft genome sequence of blood disease bacterium A2 HR-MARDI, which could provide important information on the virulence mechanism of this pathogen.


Isolation and characterization of chitinolytic bacterium, Escherichia fergusonii AMC01 from insectivorous bat, Taphozous melanopogon.
Chitinases are capable of hydrolyzing insoluble chitin into its oligo and monomeric parts and have received increased consideration because of their wide scope of biotechnological applications. The commercial application of microbial chitinase is appealing due to the relative ease of enormous production and to meet the current world demands. This study aimed at isolation and characterization of chitin degrading bacteria from the gut of Indian tropical insectivorous black-bearded tomb bat, Taphozous melanopogon. The isolated bacterial strains were characterized through biochemical analysis and nucleic acid-based approaches by 16S ribosomal RNA amplification and sequencing. The BLAST (Basic Local Alignment Search Tool) and phylogenetic analysis showed that the bacterial strain exhibited a close resemblance with Escherichia fergusonii. The chitinolytic activity of the E. fergusonii AMC01 was identified using supplemented colloidal chitin with agar medium. Compiling all, these findings would facilitate in constructing a database and presumably promote the use of E. fergusonii AMC01 as an efficient strain for the chitinase production.


p,p'-Methoxyl-diphenyl diselenide-loaded polymeric nanocapsules are chemically stable and do not induce toxicity in mice.
Organoselenium compounds have been targeted to new therapeutic tools development due to their pharmacological actions. However, some toxicity issues and physicochemical limitations delay the clinical application of these compounds. The incorporation of organoselenium molecules into nanostructured systems arises as a promising alternative to overcome such restrictions. The current study proposed the characterization of the polymeric nanocapsules of p,p'-methoxyl-diphenyl diselenide [(OMePhSe)2] as well as the evaluation of the in vivo toxicity and biodistribution profile. The nanocapsules, which were composed by medium-chain triglycerides as the oil core and poly(ε-caprolactone) as the polymeric wall, showed nanometric size (236±4), low polydispersity (<0.2), negative zeta potential (-5.4±0.06), neutral pH values (7.2±0.08) and a high encapsulation efficiency (98%). Besides, the nanoencapsulation process increased the (OMePhSe)2 stability. The repeated intragastric administration of (OMePhSe)2 nanoencapsulated (25mg/kg/day during 7days) did not cause any alteration in the oxidative status, hematological parameters, and plasma biochemical markers of cellular damage. Moreover, the (OMePhSe)2 incorporation into nanocapsules increased the selenium concentrations in the tissues (kidneys, liver and plasma) suggesting an improvement in its oral bioavailability.


Movement disturbances in the differential diagnosis of Creutzfeldt-Jakob disease.
Movement disturbances are common in dementia disorders and are a central feature of the clinical classification criteria of Creutzfeldt-Jakob disease (CJD). Polymorphism at codon 129 of the prion protein gene is known to determine the clinical picture of CJD. The frequency and characteristics of movement disturbances in other dementing disorders, such as Alzheimer's disease (AD), is barely known and leads to misdiagnoses. We investigated the occurrence and characteristics of movement disturbances in 143 patients neuropathologically confirmed with CJD (n = 100), AD (n = 29), dementia with Lewy bodies (DLB) (n = 7), or other diagnoses (n = 7). All patients had been referred with the differential diagnosis of prion disease. Ataxia and dysmetria were significantly more frequent in CJD than in AD or DLB patients, whereas hypokinesia was up to five times more frequent in AD or DLB (P < 0.05). Using an ordered logistic regression to identify constellations of movement disturbances, the diagnosis of CJD was likely in patients presenting ataxia but not hypokinesia. The reverse situation was statistically associated with AD. Ataxia and cogwheel rigidity were associated with valine-homozygosity and akinesia with methionine-homozygosity in the CJD patients. Our results indicate that the careful assessment of movement disturbances may be helpful in the differential diagnosis of Creutzfeldt-Jakob disease.


Cloning and characterization of cyclophilin C-associated protein: a candidate natural cellular ligand for cyclophilin C.
We report the protein purification and the cloning and characterization of a cDNA encoding the proteins that bind with high affinity to cyclophilin C (Cyp-C) in the absence of cyclosporin A. Transfection of this cDNA into COS cells directs the production of a glycoprotein of 77 kDa that binds to Cyp-C in the absence, but not the presence, of cyclosporin A. Homology comparisons reveal that this protein and gene, termed CyCAP for Cyp-C-associated protein, possess a cysteine-rich domain (scavenger receptor cysteine-rich domain) found in a variety of cell-surface molecules; the rest of the sequence is apparently specific. This result raises the possibility that Cyp-C serves as a mediator or regulator of an as-yet-unidentified signal or cellular process initiated via the Cyp-C-associated protein.


The diagnosis of the middle interhemispheric variant of holoprosencephaly with fetal MRI.
Congenital anomalies of the central nervous system comprise a wide spectrum of malformations associated with a wide variety of genetic syndromes and chromosomal anomalies, and they are among the principal causes of morbidity and mortality in infants. Among these anomalies, holoprosencephaly arises from the complete or partial failure of the brain to divide into the cerebral hemispheres. Imaging tests are fundamental for the prenatal diagnosis of holoprosencephaly; the diagnostic process usually starts with sonography and then the findings are refined with fetal MRI. Radiologists need to be familiar with the possible findings because the prognosis varies.


Temporal-frequency tuning of cross-orientation suppression in the cat striate cortex.
A sinusoidal mask grating oriented orthogonally to and superimposed onto an optimally oriented base grating reduces a cortical neuron's response amplitude. The spatial selectivity of cross-orientation suppression (XOR) has been described, so for this paper we investigated the temporal properties of XOR. We recorded from single striate cortical neurons (n = 72) in anesthetized and paralyzed cats. After quantifying the spatial and temporal characteristics of each cell's excitatory response to a base grating, we measured the temporal-frequency tuning of XOR by systematically varying the temporal frequency of a mask grating placed at a null orientation outside of the cell's excitatory orientation domain. The average preferred temporal frequency of the excitatory response of the neurons in our sample was 3.8 (+/- 1.5 S.D.) Hz. The average cutoff frequency for the sample was 16.3 (+/- 1.7) Hz. The average preferred temporal frequency (7.0 +/- 2.6 Hz) and cutoff frequency (20.4 +/- 6.9 Hz) of the XOR were significantly higher. The differences averaged 1.1 (+/- 0.6) octaves for the peaks and 0.3 (+/- 0.4) octaves for the cutoffs. The XOR mechanism's preference for high temporal frequencies suggests a possible extrastriate origin for the effect and could help explain the low-pass temporal-frequency response profile displayed by most striate cortical neurons.


Photoexcitation dynamics of coupled semiconducting carbon nanotube thin films.
Carbon nanotubes are a promising means of capturing photons for use in solar cell devices. We time-resolved the photoexcitation dynamics of coupled, bandgap-selected, semiconducting carbon nanotubes in thin films tailored for photovoltaics. Using transient absorption spectroscopy and anisotropy measurements, we found that the photoexcitation evolves by two mechanisms with a fast and long-range component followed by a slow and short-range component. Within 300 fs of optical excitation, 20% of nanotubes transfer their photoexcitation over 5-10 nm into nearby nanotube fibers. After 3 ps, 70% of the photoexcitation resides on the smallest bandgap nanotubes. After this ultrafast process, the photoexcitation continues to transfer on a ~10 ps time scale but to predominantly aligned tubes. Ultimately the photoexcitation hops twice on average between fibers. These results are important for understanding the flow of energy and charge in coupled nanotube materials and light-harvesting devices.


[The results of an investigation of the various factors influencing the late patency ratio of coronary bypass grafting].
The purpose of this communication was to find out the factors influencing the late patency ratio of coronary artery bypass grafts of 42 patients in our institution. The following results were obtained: 1. The size of the measured diameters of coronary arteries and the graft flow rates were correlated well to the late patency ratio (p less than 0.05). 2. The regular physical exercise trainings were significantly important to keep patent grafts (p less than 0.01). 3. In blood serum studies, serum uric acid levels were significantly lower (p less than 0.05), the average mean HDL cholesterol levels were much higher (p less than 0.001) and the ratio of total cholesterol to HDL cholesterol were significantly lower in the group with late patent grafts than with grafts occluded. Therefore, we found out the variables affecting graft patency ratio which were examined by a stepwise method were the diameter of the coronary artery, regular physical exercise training, the average of lower serum uric acid levels and higher HDL cholesterol levels. The multiple coefficient for these four variables was 0.562 (p less than 0.001) and the contribution was 31.6%. According to the base of this studies, we have concluded that postoperative regular physical exercise, low fat and restricted calorie intake were very important to keep the late patent grafts in long-term follow up period after coronary bypass surgery.


The impact of global warming on the signature virulence gene, thermolabile hemolysin, of Vibrio parahaemolyticus.
Global warming is increasing human exposure to pathogens and has already had an impact on human health. Vibrio parahaemolyticus, a major pathogen causing foodborne illness, accumulates in numerous aquatic organisms and can be affected by environmental stressors such as increased replication errors or DNA damage resulting in point mutations. This could lead to an elevation in the mutation rate, which influences the expansion of Vibrio spp. habitats and the spread of associated diseases. In this study, a total of 241 strains were isolated from aquatic products imported or exported through China Customs between 2005 and 2010. The whole genomes of those strains were sequenced, revealing a highly significant level of genetic diversity. Our analysis identified 27 new sequence types (STs) ranging from ST2950 to ST2976. The global temperature trend since 1950 affects the thermolabile hemolysin gene (tlh) found in all Vibrio parahaemolyticus leading to mutant sites exhibiting similar trends as temperatures rise; seven high-frequency mutation hotspots (A180G, T552G, G657T, T858C, C1062T, A1137G, and T1179C) were identified along with two clinically specific sites (T259C and A951T) that may indicate adaptation over time due to climate change, leading to increased virulence potential for this bacterial species. These results provide insight into the genetics of Vibrio parahaemolyticus and provide a reference for subsequent research, identification, and monitoring efforts related to its spread. IMPORTANCE In this study, Vibrio parahaemolyticus strains were collected from a large number of aquatic products globally and found that temperature has an impact on the virulence of these bacteria. As global temperatures rise, mutations in a gene marker called thermolabile hemolysin (tlh) also increase. This suggests that environmental isolates adapt to the warming environment and become more pathogenic. The findings can help in developing tools to analyze and monitor these bacteria as well as assess any link between climate change and vibrio-associated diseases, which could be used for forecasting outbreaks associated with them.


Therapeutic application of intravenous human natural immunoglobulin preparation.
Human natural immunoglobulin (HunIg) preparation for intravenous use has been used in various diseases. The most typical application of this preparation is agammaglobulinemia. Currently, however, this preparation is being used in the therapy of many other disorders. These include thrombocytopenia, Kawasaki disease, systemic vasculitis, several other disorders of autoimmune origin and systemic inflammation such as sepsis. In some diseases, the clinical improvement following use of HunIg has been dramatic, while in others its effect is not striking. Due to rarity of the side effects, the range of application of HunIg has been recently broadened. Such side effects include transmission of several diseases such as hepatitis and retroviral infections. Before it is recommended for use, however, and primarily due to expense, the efficacy of this drug should be carefully evaluated. The mechanism of action of HunIg is not fully understood. However, it has been suggested that its action may involve blockade of Fc-receptor, an anti-cytokine effect, or inhibition of complement activation. In this review, the mechanism of action of HunIgG and its application in human diseases are discussed.


Heterogeneity in readouts of canonical wnt pathway activity within intestinal crypts.
Canonical Wnt pathway signaling is necessary for maintaining the proliferative capacity of mammalian intestinal crypt base columnar stem cells (CBCs). Furthermore, dysregulation of the Wnt pathway is a major contributor to disease, including oncogenic transformation of the intestinal epithelium. Given the critical importance of this pathway, numerous tools have been used as proxy measures for Wnt pathway activity, yet the relationship between Wnt target gene expression and reporter allele activity within individual cells at the crypt base remains unclear. Here, we describe a novel Axin2-CreERT2-tdTomato allele that efficiently marks both Wnt(High) CBCs and radioresistant reserve intestinal stem cells. We analyze the molecular and functional identity of Axin2-CreERT2-tdTomato-marked cells using single cell gene expression profiling and tissue regeneration assays and find that Axin2 reporter activity does not necessarily correlate with expression of Wnt target genes and, furthermore, that Wnt target genes themselves vary in their expression patterns at the crypt base. Wnt target genes and reporter alleles can vary greatly in their cell-type specificity, demonstrating that these proxies cannot be used interchangeably. Furthermore, Axin2-CreERT2-tdTomato is a robust marker of both active and reserve intestinal stem cells and is thus useful for understanding the intestinal stem cell compartment. Developmental Dynamics 245:822-833, 2016. © 2016 Wiley Periodicals, Inc.


Return to dialysis after renal transplantation. Which would be the best way?
The exact moment to return to dialysis when a graft fails has not clearly been established. Furthermore, there is no agreement with respect to whether the guidelines accepted for patients entering dialysis for the first time are adequate for this subgroup of patients with advanced renal failure, due to the special characteristics of these patients, derived from the immunosuppressive medications they are taking among other accompanying factors. We reviewed a group of renal transplant patients who returned to dialysis and compared them with a group of patients entering dialysis for the first time. Patients with chronic renal failure due to graft failure had a poorer renal function at the time entering dialysis and a more profound anemia. Additionally, complications considered such as the number of hospital admissions during the first year after initiation of dialysis were considerably higher in the group of transplanted patients. We advocate for an earlier referral to the dialysis unit, a more aggressive erythropoietin therapy in the phase of advanced renal failure due to chronic allograft nephropathy, and in selected cases retransplantation before definitive graft loss.


Characterization of cell-associated and soluble forms of connective tissue growth factor (CTGF) produced by fibroblast cells in vitro.
Connective tissue growth factor (CTGF) is a mitogenic and chemotactic factor for cultured fibroblasts that has been implicated in wound healing, fibrotic disorders and uterine function. Although the primary translational products of the mouse, human and pig CTGF (mCTGF, hCTGF, pCTGF) genes are predicted to be secreted and of approximate M(r) 38,000, 10 kDa biologically active forms of pCTGF have recently been described. In this report, we show that human foreskin fibroblasts (HFFs) and mouse connective tissue fibroblasts contained 2.4 kb CTGF transcripts, stained positively with an anti-CTGF[81-94] peptide antiserum, and produced a 38 kDa protein that was immunoprecipitated by an anti-CTGF[247-260] peptide antiserum. While 38 kDa CTGF was readily detected in cell lysates, it was non- or barely detectable in conditioned medium. 38 kDa CTGF remained cell-associated for at least 5 days after synthesis and was not releasable by treatment of the cells with trypsin, heparin, 1 M NaCl or low pH. Purification of CTGF from human or mouse fibroblast conditioned medium resulted in the isolation of 10-12 kDa CTGF proteins that were heparin-binding, bioactive, and reactive with anti-CTGF[247-260] on Western blots. Whereas 10 kDa CTGF stimulated DNA synthesis in 3T3 cells to the same extent as platelet-derived growth factor (PDGF)-AA, -AB, or -BB, it did not compete with 125I-PDGF-BB for binding to alpha alpha, alpha beta or beta beta PDGF receptors (PDGF-R), did not stimulate tyrosine phosphorylation of PDGF-alpha-R or -beta-R, and was not antagonized by a neutralizing PDGF-R-alpha antiserum. These data show that, in cultured fibroblasts, 38 kDa CTGF is principally cell-associated whereas low mass forms of CTGF are soluble and biologically active. They further demonstrate that, contrary to the previously proposed properties of 38 kDa CTGF, 10 kDa CTGF does not bind to PDGF-R and stimulates Balb/c 3T3 cell mitosis via a PDGF-R-independent mechanism.


Study on the transfection efficiency of chitosan-based gene vectors modified with poly-l-arginine peptides.
Although in a series of studies, arginine peptides had shown the ability to promote the targeting delivery efficacy, the relationship between the transfection efficiency and the length of the poly-l-arginine chain had seldom been reported. This study was aimed to explore whether the chain length of poly-l-arginine grafted on chitosan had a great significance on the transfection efficiency of entering the cells. Herein, arginine and arginine peptide modified chitosan were synthesized as gene vectors (CS-Arg and CS-5Arg) and then the chemical structures were characterized by using 1 H NMR. The CS-Arg and CS-5Arg were combined with plasmids by electrostatic interactions to form stable particles. The morphology features, Zeta potentials, and buffering capacity of the complex particles were analyzed. Afterward, the combination ability with DNA and the protection ability to DNase I were studied, and the gene transfection efficiency and cellular uptake were investigated in vitro. The results showed that the gene transfection efficiency of the chitosan was significantly enhanced by arginine-graft modification. However, there were no significant differences between the CS-Arg and the CS-5Arg. The molecular simulation results indicated that the guanidine groups of grafted arginine were shielded by chitosan molecule and the guanidine groups contributed little to the gene transfection efficiency. The results demonstrated that the increased chain length of grafted arginine had no significantly enhanced effect on the transfection efficiency, which could provide convincing evidence for the construction and application of arginine and chitosan derivatives as gene vectors, and could promote the development of gene delivery system.


Correlation between immune and vascular activities of xanthenone acetic acid antitumor agents.
To determine whether xanthenone acetic acid (XAA) analogues of flavone acetic acid (FAA) have similar ischemic and nonischemic mechanisms of antitumor action to FAA, a series of such compounds was evaluated in vivo and in vitro. Necrotising activity and changes in tumor blood flow were measured in Colon 38 tumors, and morphological changes assessed in immune cell-infiltrated EMT6 tumor cell spheroids, after treatment with FAA, XAA and its derivatives (5-methyl XAA, 5,6-dimethyl XAA, 3-O-methyl XAA, 8-methyl XAA and xanthenone-4,5-diacetic acid). FAA, XAA and the 5-methyl and 5,6-dimethyl analogues of XAA were active in inducing tumor necrosis, falls in tumor perfusion and characteristic morphological changes in multicellular spheroids. The other XAA analogues lacked these activities. 5-methyl XAA and 5,6-dimethyl XAA were more potent than FAA or XAA. The results suggest that XAA and its analogues have the same mechanisms of action as FAA, and that both the vascular and the immune effects of these compounds are mediated via a common biochemical receptor.


Hephaestia mangrovi sp. nov., a novel endophytic bacterium isolated from Aegiceras corniculatum.
A Gram-stain-negative, aerobic, motile, rod-shaped bacterium, designated CMS5P-6T, was isolated from a surface-sterilized bark of Aegiceras corniculatum collected from Guangxi Zhuang Autonomous Region, PR China, and investigated by a polyphasic approach to determine its taxonomic position. Strain CMS5P-6T was found to grow optimally with 0-1 % (w/v) NaCl, at 30 °C and pH 6.0-7.0. Substrate mycelia and aerial mycelia were not formed, and no diffusible pigments were observed on the media tested. Phylogenetic analysis showed that strain CMS5P-6T showed high 16S rRNA gene sequence similarity of 96.7 % to Hephaestia caeni DSM 25527T and Sphingomonas colocasiea CC-MHH0539T. The average nucleotide identity, digital DNA-DNA hybridization and average amino acid identity values between strain CMS5P-6T and H. caeni DSM 25527T were 78.0, 21.7 and 70.8 %, respectively. The average nucleotide identity, digital DNA-DNA hybridization and average amino acid identity values between strain CMS5P-6T and S. colocasiea JCM 31229T were 74.0, 19.9 and 61.4 %, respectively. Phylogenomic analyses based on genome sequences showed that strain CMS5P-6T and H. caeni DSM 25527T formed a distinct cluster within the family Sphingomonadaceae and far away from S. colocasiea JCM 31229T. The DNA G+C content of strain CMS5P-6T was determined to be 65.6 mol%. The cell-wall peptidoglycan was found to contain meso-diaminopimelic acid as the diagnostic diamino acid and ubiquinone Q-10 was identified as the respiratory lipoquinone. The polar lipids were found to comprise diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, sphingoglycolipid and two unidentified aminolipids, and the major fatty acids were identified as C18 : 1 ω7c, C19 : 0 cycloω8c and C16 : 0. On the basis of phylogenetic, genomic, chemotaxonomic and phenotypic data, strain CMS5P-6T can be concluded to represent a novel species of the genus Hephaestia, for which the name Hephaestia mangrovi sp. nov. is proposed. The type strain is CMS5P-6T (=JCM 33125T=CGMCC 1.13868T).


Effects of enriched environment and fluid percussion injury on dendritic arborization within the cerebral cortex of the developing rat.
We have recently demonstrated that fluid percussion injury (FPI) sustained early in life prevents the neural plasticity response associated with rearing in an enriched environment (EE). In order to determine if this reduction in plasticity capacity is reflected in alterations in dendritic arborization, the present study examined dendritic changes in response to EE, FPI, and FPI followed by EE. Twenty postnatal day 19-20 rat pups were subjected to FPI or sham injury and were subsequently housed in EE (17 days) or standard conditions. Brains were processed according to the Golgi-Cox method and were analyzed using dendritic density (Sholl) and dendritic branching analyses in frontal, parietal, and occipital cortices. Rearing in EE induced an increase in dendritic density, primarily within the occipital cortex. FPI induced an increase in dendritic density, primarily in regions remote from the injury site, namely contralateral parietal cortex and ipsilateral and contralateral occipital cortex. In injured animals subsequently housed in EE, FPI appeared to inhibit the experience-dependent dendritic density effects of EE. However, an unexpected enhancement of dendritic density was seen in the ipsilateral occipital cortex, indicating a unique response of this region based on its distance-specific sensitivity to injury-induced plasticity and its region-specific sensitivity to experience-dependent plasticity. These results suggest that dendritic changes mediate the anatomical and behavioral changes characteristic of impaired developmental plasticity following FPI, and that these changes are dependent on location within the cerebral cortex.


Risk factors for recurrent melioidosis in northeast Thailand.
Recurrent melioidosis occurs in approximately 6% of patients in the first year following the initial presentation. A recent study revealed that 25% of patients with recurrence had reinfection rather than a relapse resulting from a failure to cure. The aim of this study was to reevaluate these 2 patient groups to define their individual risk factors. All adult patients who presented to Sappasithiprasong Hospital (Ubon Ratchathani, in northeast Thailand) with culture-confirmed melioidosis during the period 1986-2004 and who survived to receive oral antimicrobial therapy were observed until July 2005. Clinical factors and antimicrobial treatment of patients with recurrent disease due to relapse or reinfection, as confirmed by bacterial genotyping, were compared using a time-varying Cox proportional hazard model. Of 889 patients who survived and underwent follow-up, 86 patients (9.7%) presented with relapse, and 30 patients (3.4%) became reinfected. There was no difference in acute outcome between the relapse and reinfection groups. No risk factors for reinfection were identified. Multivariate analyses identified choice and duration of oral antimicrobial therapy as the most important determinants of relapse, followed by positive blood culture result (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.18-2.92) and multifocal distribution (HR, 1.95; 95% CI, 1.03-3.67). Patients treated with an appropriate oral antibiotic regimen for 12-16 weeks had a 90% decreased risk of relapse (HR, 0.10; 95% CI, 0.02-0.44), compared with patients who were treated for < or = 8 weeks. Trimethoprim-sulfamethoxazole plus doxycycline was an effective oral therapy. This study highlights clinical factors associated with an increased likelihood of relapse and provides evidence for optimal oral antimicrobial therapy.


The Pyruvate-Phosphate Dikinase (C4-SmPPDK) Gene From Suaeda monoica Enhances Photosynthesis, Carbon Assimilation, and Abiotic Stress Tolerance in a C3 Plant Under Elevated CO2 Conditions.
A pyruvate-phosphate dikinase (C4-PPDK) gene was cloned from Suaeda monoica, which had a single-cell C4 photosynthesis pathway without Kranz anatomy and was functionally validated in a C3 model plant under different abiotic stress conditions in an ambient and elevated CO2 environment. Overexpression of SmPPDK promoted growth of C3 transgenic plants, enhancing their photosynthesis (CO2 assimilation) by lowering photorespiration under stress conditions. Transgenic plants also showed an improved physiological status, with higher relative water content (RWC), membrane integrity, concentration of glycine betaine, total soluble sugars, free amino acids, polyphenols and antioxidant activity, and lower electrolyte leakage, lipid peroxidation, free radical accumulation, and generation of reactive oxygen species (ROS), compared to control plants. Moreover, SmPPDK transgenic plants exhibited earlier flowering and higher dry biomass compared to controls. These results suggested that the C4-PPDK gene was appropriate for improvement of carbon assimilation, and it also played an important role in adaption to salinity and severe drought-induced stress. More intriguingly, an elevated CO2 environment alleviated the adverse effects of abiotic stress, particularly caused by drought through coordination of osmoprotectants and antioxidant defense systems. The molecular, physiological, metabolic, and biochemical indicators ameliorated the overall performance of model C3 plants overexpressing the C4-PPDK gene in an elevated CO2 environment, by lowering photorespiration metabolic processes, however, further studies are needed to confirm its precise role in C3 plants as protection against future climate change.


Examining the word identification stages hypothesized by the E-Z Reader model.
A critical prediction of the E-Z Reader model is that experimental manipulations that disrupt early encoding of visual and orthographic features of the fixated word without affecting subsequent lexical processing should influence the processing difficulty of the fixated word without affecting the processing of the next word. We tested this prediction by monitoring participants' eye movements while they read sentences in which a target word was presented either normally or altered. In the critical condition, the contrast between the target word and the background was substantially reduced. Such a reduction in stimulus quality is typically assumed to have an impact that is largely confined to a very early stage of word recognition. Results were consistent with the E-Z Reader model: This faint presentation had a robust influence on the duration of fixations on the target word without substantially altering the processing of the next word.


Thermodynamic and structural analysis of peptide- and allele-dependent properties of two HLA-B27 subtypes exhibiting differential disease association.
Selected HLA-B27 subtypes are associated with spondyloarthropathies, but the underlying mechanism is not understood. To explain this association in molecular terms, a comparison of peptide-dependent dynamic and structural properties of the differentially disease-associated subtypes HLA-B*2705 and HLA-B*2709 was carried out. These molecules differ only by a single amino acid at the floor of the peptide binding groove. The thermostabilities of a series of HLA-B27 molecules complexed with nonameric and decameric peptides were determined and revealed substantial differences depending on the subtype as well as the residues at the termini of the peptides. In addition we present the crystal structure of the B*2709 subtype complexed with a decameric peptide. This structure provides an explanation for the preference of HLA-B27 for a peptide with an N-terminal arginine as secondary anchor and the lack of preference for tyrosine as peptide C terminus in B*2709. The data show that differences in thermodynamic properties between peptide-complexed HLA-B27 subtypes are correlated with a variety of structural properties.


[The study of the association between lung cancer screening and smoking behavior change].
The smoking cessation rate of 1 314 people at high risk of lung cancer in the area of lung cancer screening and early diagnosis and early treatment in Sichuan Province increased from 22.37% at baseline to 41.78% after screening (χ²=227.97, P<0.001), and the smoking amount of persistent smokers decreased from 20 cigarettes per day to 15 cigarettes per day (t=11.76, P<0.001). Those with positive results in lung cancer screening were more likely to quit smoking or continue to quit smoking. Male, younger age or lower education level would increase the risk of continuous smoking or relapse (P<0.05).


Characterizing the Multidrug Resistance of non-O157 Shiga Toxin-Producing Escherichia coli Isolates from Cattle Farms and Abattoirs.
Non-O157 Shiga toxin-producing Escherichia coli (STECs) are not as well characterized as O157 STEC cases, despite their similar prevalence in many countries. Hence, the objective of this study was to investigate the phenotypic and genotypic basis of multidrug resistance (MDR) in non-O157 STEC farm- and abattoir-sourced isolates and assess the potential dissemination of these MDR profiles in vitro. Susceptibility testing to 20 antimicrobials was performed on 146 non-O157 STECs isolated from farm and abattoir environments. Eighty-seven percent of non-O157 STEC isolates were multidrug resistant to antimicrobials used during veterinary and agricultural practice. Antimicrobial resistance was significantly higher in abattoir isolates compared with the farm isolates (p < 0.05). Corresponding resistance determinants and integrons were investigated by polymerase chain reaction, with the predominant resistance determinants detected being floR, ampC, tet(A), blaTEM, and sul1. This is the first report of tet(G) in a non-O157 STEC isolate. Class 1 integrons were detected in 17 isolates. Resistance to ampicillin, cephalothin, chloramphenicol, kanamycin, neomycin, sulfonamides, trimethoprim, and tetracycline was associated with transferable plasmids belonging to incompatibility groups IncP, IncB/O, and IncFIB. Most MDR non-O157 STECs (90%) isolated in this study belong to phylogenetic groups A and B1. These findings suggest that MDR non-O157 STECs are emerging as a result of nonpathogenic E. coli acquiring virulence and resistance genes. This may convey a certain competitive advantage in the colonization of cattle when antimicrobial selective pressures are present, thereby leading to an increase in contamination of food with MDR non-O157 STECs.


AKR1B1 promotes basal-like breast cancer progression by a positive feedback loop that activates the EMT program.
Basal-like breast cancer (BLBC) is associated with high-grade, distant metastasis and poor prognosis. Elucidating the determinants of aggressiveness in BLBC may facilitate the development of novel interventions for this challenging disease. In this study, we show that aldo-keto reductase 1 member B1 (AKR1B1) overexpression highly correlates with BLBC and predicts poor prognosis in breast cancer patients. Mechanistically, Twist2 transcriptionally induces AKR1B1 expression, leading to nuclear factor κB (NF-κB) activation. In turn, NF-κB up-regulates Twist2 expression, thereby fulfilling a positive feedback loop that activates the epithelial-mesenchymal transition program and enhances cancer stem cell (CSC)-like properties in BLBC. AKR1B1 expression promotes, whereas AKR1B1 knockdown inhibits, tumorigenicity and metastasis. Importantly, epalrestat, an AKR1B1 inhibitor that has been approved for the treatment of diabetic complications, significantly suppresses CSC properties, tumorigenicity, and metastasis of BLBC cells. Together, our study identifies AKR1B1 as a key modulator of tumor aggressiveness and suggests that pharmacologic inhibition of AKR1B1 has the potential to become a valuable therapeutic strategy for BLBC.


Parent Ratings of the Strengths and Difficulties Questionnaire: What Is the Optimum Factor Model?
To date, at least 12 different models have been suggested for the Strengths and Difficulties Questionnaire (SDQ). The current study used confirmatory factor analysis to examine the relative support for these models. In all, 1,407 Malaysian parents completed SDQ ratings of their children (age range = 5-13 years). Although the findings showed some degree of support for all 12 models, there was most support for an oblique six-factor model that included the five SDQ domains (emotional problems, conduct problems, hyperactivity, peer problems, and low prosocial behavior) and a positive construal factor comprising all the 10 SDQ positive worded items. The original proposed five-factor oblique model also showed good fit. The implications of the findings for understanding the results of past studies of the structural models of the parent version of the SDQ, and for clinical and research practice involving the SDQ are discussed.


A 180 nm CMOS analog adaptive sampler for blood pressure feature extraction.
This paper presents an analogue feature detector for extraction and sampling of key-points on an arterial blood pressure signal in both humans and small mammals used as human physiological models. A CMOS integrated circuit was implemented in UMC 180nm technology, utilizing the proposed sampling method to greatly reduce the number of samples necessary for meaningful reconstruction of the low bandwidth signal. This circuit was interfaced with an external ADC to fully extract the feature points, and evaluate the system performance. Over the target heart rate range of 1 to 25 Hz, the system outperformed typical home measurement tools for systole and diastole extraction.


Ubiquitylation-dependent negative regulation of WASp is essential for actin cytoskeleton dynamics.
The Wiskott-Aldrich syndrome protein (WASp) is a key regulator of actin dynamics during cell motility and adhesion, and mutations in its gene are responsible for Wiskott-Aldrich syndrome (WAS). Here, we demonstrate that WASp is ubiquitylated following T-cell antigen receptor (TCR) activation. WASp phosphorylation at tyrosine 291 results in recruitment of the E3 ligase Cbl-b, which, together with c-Cbl, carries out WASp ubiquitylation. Lysine residues 76 and 81, located at the WASp WH1 domain, which contains the vast majority of WASp gene mutations, serve as the ubiquitylation sites. Disruption of WASp ubiquitylation causes WASp accumulation and alters actin dynamics and the formation of actin-dependent structures. Our data suggest that regulated degradation of activated WASp might be an efficient strategy by which the duration and localization of actin rearrangement and the intensity of T-cell activation are controlled.


Enzymatic functionalization of aromatic N-heterocycles: hydroxylation and carboxylation.
Aromatic N-heterocycles are common structural motifs and versatile building blocks for the synthesis of various biologically active compounds. The application of microbial catalysis is considerably advantageous for the synthesis of N-heterocycle derivatives. Recent progress in the microbial functionalization of aromatic N-heterocyclic compounds is reviewed, focusing on the regiospecific hydroxylation and the carboxylation of aromatic N-heterocycles.


The bi-loop, a new general four-stranded DNA motif.
The crystal structure of the cyclic octanucleotide d<pATTCATTC> contains two independent molecules that form a novel quadruplex by means of intermolecular Watson-Crick A.T pairs and base stacking. A virtually identical quadruplex composed of G.C pairs was found by earlier x-ray analysis of the linear heptamer d(GCATGCT), when the DNA was looped in the crystal. The close correspondence between these two structures of markedly dissimilar oligonucleotides suggests that they are both examples of a previously unrecognized motif. Their nucleotide sequences have little in common except for two separated 5'-purine-pyrimidine dinucleotides forming the quadruplex, and by implication these so-called "bi-loops" could occur widely in natural DNA. Such structures provide a mechanism for noncovalent linking of polynucleotides in vivo. Their capacity to associate by base stacking, demonstrated in the crystal structure of d(GCATGCT), creates a compact molecular framework made up of four DNA chains within which strand exchange could take place.


Application of indirect immunofluorescence to detection of Dientamoeba fragilis trophozoites in fecal specimens.
An indirect fluorescent-antibody (IFA) assay was carried out to examine for the presence of Dientamoeba fragilis trophozoites in preserved fecal specimens. Antiserum to D. fragilis trophozoites was raised in a rabbit with a dixenic culture of D. fragilis (ATCC 30948) from the American Type Culture Collection. After absorption with Klebsiella pneumoniae and Bacteroides vulgatus, the immune rabbit serum was used for examination by the IFA assay. A total of 155 clinical samples were tested; 42 with no parasites, 9 with D. fragilis, and 104 with other parasites. The IFA assay identified seven D. fragilis organisms. Two specimens with doubtful IFA assay readings showed very scanty amounts of D. fragilis trophozoites on stained smears. There were no false-positive IFA assay readings. The IFA assay appeared to be a promising method because of its speed in screening. The specificity of the IFA assay indicates that other diagnostic tests such as an enzyme-linked immunosorbent assay could be developed to identify D. fragilis antigens in fecal specimens.


Cytotoxic and radiosensitizing effects of hypoxic cell sensitizers on EMT6 mouse mammary tumour cells in vivo and in vitro.
The radiosensitizing activities and toxicities of misonidazole, metronidazole, 2-Methythio-3-nitropyrrole (3NPR), 2-amino-5-nitrothiazole (ANT) and 2,5-dinitroimidazole (KA121) were studied using EMT6 tumour cells and BALB/c KaRw mice. For 10(-4)M concentrations of the drugs, the DMF's for hypoxic cells were: Misonidazole, 1.6; 3NPR, 1.5, ANT, 1.5; KA121, 1.8. The OER was 3.2. In general, the drugs were toxic to hypoxic cells and were not toxic to aerobic cells at 10(-3)M for 24 h. The LD50's in BALB/c KaRw mice were: misonidazole, 1500 mg/kg; 3NPR, 350 mg/kg ANT, 420 mg/kg. In vivo, 1 mg/g misonidazole or metronidazole reduced the terminal slope of the tumour cell survival curve by a factor of 2.2 or 1.6 respectively.


Astrocytes Promote Oligodendrogenesis after White Matter Damage via Brain-Derived Neurotrophic Factor.
Oligodendrocyte precursor cells (OPCs) in the adult brain contribute to white matter homeostasis. After white matter damage, OPCs compensate for oligodendrocyte loss by differentiating into mature oligodendrocytes. However, the underlying mechanisms remain to be fully defined. Here, we test the hypothesis that, during endogenous recovery from white matter ischemic injury, astrocytes support the maturation of OPCs by secreting brain-derived neurotrophic factor (BDNF). For in vitro experiments, cultured primary OPCs and astrocytes were prepared from postnatal day 2 rat cortex. When OPCs were subjected to chemical hypoxic stress by exposing them to sublethal CoCl2 for 7 d, in vitro OPC differentiation into oligodendrocytes was significantly suppressed. Conditioned medium from astrocytes (astro-medium) restored the process of OPC maturation even under the stressed conditions. When astro-medium was filtered with TrkB-Fc to remove BDNF, the BDNF-deficient astro-medium no longer supported OPC maturation. For in vivo experiments, we analyzed a transgenic mouse line (GFAP(cre)/BDNF(wt/fl)) in which BDNF expression is downregulated specifically in GFAP(+) astrocytes. Both wild-type (GFAP(wt)/BDNF(wt/fl) mice) and transgenic mice were subjected to prolonged cerebral hypoperfusion by bilateral common carotid artery stenosis. As expected, compared with wild-type mice, the transgenic mice exhibited a lower number of newly generated oligodendrocytes and larger white matter damage. Together, these findings demonstrate that, during endogenous recovery from white matter damage, astrocytes may promote oligodendrogenesis by secreting BDNF. The repair of white matter after brain injury and neurodegeneration remains a tremendous hurdle for a wide spectrum of CNS disorders. One potentially important opportunity may reside in the response of residual oligodendrocyte precursor cells (OPCs). OPCs may serve as a back-up for generating mature oligodendrocytes in damaged white matter. However, the underlying mechanisms are still mostly unknown. Here, we use a combination of cell biology and an animal model to report a new pathway in which astrocyte-derived BDNF supports oligodendrogenesis and regeneration after white matter damage. These findings provide new mechanistic insight into white matter physiology and pathophysiology, which would be broadly and clinically applicable to CNS disease.


The exstrophy-epispadias complex in the duplicated lower urinary tract.
The exstrophy-epispadias complex in combination with a duplicated lower urinary tract is an extremely rare congenital malformation. We describe 2 cases of bladder exstrophy in association with a duplicated lower urinary tract. We analyzed the case histories of 2 patients. The first case had anteroposterior duplication of the bladder communicating through an isthmus and a duplicate urethra. The anterior system was exstrophic and epispadiac. The second case had a duplicate bladder without epispadias. There was a communication between the anterior exstrophic and posterior normal bladders. No other malformations were present. Both patients underwent excision of the duplicate exstrophic bladder in conjunction with primary closure of the abdominal wall. Postoperative continence was normal. Histological examination confirmed the diagnosed bladder duplication. Although duplication of the lower urinary tract in combination with the exstrophy-epispadias complex is extremely rare, all children presenting with an exstrophic bladder and a normal urethra alone or in association with an epispadiac anterior urethra should be evaluated for a bladder duplication with possible isthmic communication.


The relationship between CEA and CA 15-3 positivity and metabolic and volumetric 18F-FDG PET/CT parameters in preoperative evaluation of breast cancer.
We aimed to examine the relationship between tumor marker (Cancer Antigen 15-3 [CA15-3] and Carcinoembryonic Antigen [CEA]) positivity and metabolic (standardized uptake value [SUV]) and volume-based (metabolic tumor volume [MTV] and total lesion glycolysis [TLG]) 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) parameters of the primary tumor and lymph node. Our study group consisted of 91 female patients, who underwent PET/CT between January 2018 and December 2019 in our clinic with a diagnosis of breast cancer. These patients had no distant metastasis or supraclavicular and internal mammarian lymph node metastasis. MTV, TLG, and SUVmax values were obtained from the primary breast lesion and axillary lymph nodes. The mean age of the patients, who participated in the study, was 52,19±14,57, and the median values of the primary tumor MTV, TLG, and total MTV values were found to be statistically significantly higher in those who were CEA positive compared to those who were CEA negative. The median SUVmax value of the axillary lymph node was found to be statistically significantly higher in those who were CEA positive compared to those who were CEA negative (p: 0.004). There was no statistically significant difference between the other parameters. There was a statistically significant correlation between CEA positivity in preoperative primary breast cancer and primary tumor volume MTV, TLG, and total MTV values, which are volume-based PET parameters. CEA positivity evaluation may indicate increased tumor load in preoperative. Breast Cancer, CEA, CA 15-3, MTV, TLG, FDG PET/CT.


Losing a training analyst for ethical violations: a candidate's perspective.
The author presents her experience as the analysand of a training analyst who was investigated and expelled for ethical violations with another patient, including sexual-boundary violations, during her analytic training. While boundary violations by training analysts are not uncommon, the particular trauma experienced by 'bystanders' such as candidates and supervisees is not discussed in the literature, nor the response of institutes to the educational problems that are generated. The author illustrates the complications for candidates that arise from the dual roles of training analyst as educator and analyst when he or she faces investigation or censure, including isolation and secrecy, which promote various splits in the candidate, analytic dyad and group, as well as loyalty conflicts. The discussion covers three phases of the author's experience as a candidate-analysand, namely the period encompassing the institute's ethics investigation, the announcement of findings to her and to the institute as a group, and the ensuing individual and group dynamics generated by her analyst's expulsion from the institute and revocation of his medical license. Theoretical perspectives are utilized to understand the group regression, including contamination and contagion fears, which occurred in the wake of the training analyst's expulsion, and the impact of these processes on the candidate, including the pressure to function as a 'container' for projections of the group. Implications and recommendations for candidates and institutes are made for dealing helpfully with trainees who are affected by the process of dealing with a training analyst's ethical violations. Short-term and longer-term outcomes of the experience are considered.


A worldwide comparison of long-distance running training in 2019 and 2020: associated effects of the COVID-19 pandemic.
The goal of the present study was to investigate possible effects of the COVID-19 pandemic on long-distance running training. This is a retrospective study with a within-subject design. We analyzed 10,703,690 records of running training during 2019 and 2020, from 36,412 athletes from around the world. The records were obtained through web scraping of a large social network for athletes on the internet. A potential long-distance runner was defined as a user of the social network who had a record of running at least one of the six World Marathon Majors by 2019. In 2020, compared with 2019, in total there was a 3.6% decrease in the number of athletes running, a 7.5% decrease in the distance and 6.7% in the duration of running training. There were large variations in these variables throughout 2020, reaching 16% fewer athletes running weekly and 35% lower running distance (Cohen's d = 0.34, p < 0.001) and 33% lower running duration (Cohen's d = 0.30, p < 0.001) in September 2020. The beginning of the decrease in running training in the first quarter of 2020 coincides with the beginning of the adoption of measures to restrict the COVID-19 pandemic; but as of the second quarter of 2020, running training appears to have undergone variations unrelated to the preventive measures. Among the ten most represented countries in the dataset, running training in Brazil appears to have been the most affected by the COVID-19 pandemic and restriction measures. The wide variations in long-distance running training throughout 2020 are likely related to the COVID-19 pandemic. As for the total volume, the observed decreases of up to 7.5% in the outcome variables related to running training in 2020 could also be attributed to the COVID-19 pandemic, but other factors such as injury, illness or lack of interest, may also have contributed to these decreases.


Chronic inflammatory periapical diseases: a Brazilian multicenter study of 10,381 cases and literature review.
The aim of this study was to investigate the epidemiological and clinical characteristics of chronic inflammatory periapical diseases in different regions of Brazil and to compare with data from the literature. A multicenter study was carried out in four Brazilian referral centers in oral diagnosis. Histopathological records were reviewed, and all cases diagnosed microscopically as periapical granuloma, radicular cyst, and periapical abscess were included. Demographic and clinical data were collected. Descriptive statistics and Pearson's chi-square test were performed. A total of 10,381 cases of chronic inflammatory periapical diseases were found (13.8% of 74,931 archived specimens) over a period of 65 years. Radicular cysts were the most common lesion (59.9%). Women (56.1%) with a mean age of 37.01 years old (range 13 to 100 ± 14.42) and people of white skin color (59.2%) were the most affected individuals by chronic inflammatory periapical diseases. The lesions were generally asymptomatic (28.1%), located in the maxilla (60.1%), and posterior region (49.8%). The radicular cysts were larger when compared to periapical granulomas (p < 0.001). The disagreement between the clinical and histopathological diagnoses was higher when the final diagnosis was a periapical granuloma (p < 0.001). Chronic inflammatory periapical diseases continue to be common lesions affecting mainly adults. This should be a consequence of the burden of untreated caries in permanent teeth. Women are more affected and radicular cyst was the most common lesion.


Segmented retinal analysis in pituitary adenoma with chiasmal compression: A prospective comparative study.
The aim of this study was to determine the alteration in ganglion cell complex and its relationship with retinal nerve fiber layer (RNFL) thickness as measured by spectral-domain optical coherence tomography (OCT) in pituitary adenoma cases and also its correlation with visual field (VF). This is a prospective comparative study wherein detailed neuro-ophthalmic examination including perimetry, RNFL and ganglion cell layer inner plexiform layer (GCL-IPL) thickness were measured preoperatively in the cases of pituitary adenoma with chiasmal compression with visual symptoms and field changes who were planned for neuro-surgical intervention. These parameters were repeated 1 year after the surgery. GCL-IPL, RNFL parameters were compared with controls and were correlated with VF mean deviation (MD). The diagnostic power of GCL-IPL was tested using the receiver operating characteristic (ROC) curve. Healthy age and sex-matched controls without any ocular and systemic abnormality were taken for comparison. Twenty-four patients qualified the inclusion criteria. A significant thinning of GCL-IPL (P = 0.002) and RNFL (P = 0.039) was noticed in the pituitary adenoma group. GCL-IPL (r = 0.780 P < 0.001) and RNFL (r = 0.669, P < 0.001) were significantly correlated with the MD. The ROC curve values of GCL-IPL were 0.859 (95% confidence interval 0.744% to 0.973) and of RNFL were 0.731 (95% confidence interval 0.585-0.877). The diagnostic ability of GCL-IPL was more as compared to the RNFL analysis, although it was statistically insignificant (P = 0.122). GCL-IPL measurements on the OCT are a sensitive tool to detect early anterior visual pathway changes in chiasmal compression for pituitary adenoma patients.


Investigation of the effectiveness of the "Girls on the Go!" program for building self-esteem in young women: trial protocol.
Body Image is a major factor affecting health in a range of age groups, but has particular significance for adolescents. The aim of this research is to evaluate the efficacy of the "Girls on the Go!" program delivered outside of the school environment by health professionals to girls at risk of developing poor self-esteem on the outcomes of self-esteem, impairment induced by eating disorders, body satisfaction, self-efficacy, and dieting behaviour. A stepped wedge, cluster randomised controlled trial that was conducted in two phases on the basis of student population (Study 1 = secondary school age participants; Study 2 = primary school age participants). The waiting list for the "Girls on the Go!" program was used to generate the control periods. A total of 12 schools that requested the program were separated into study 1 or 2 on the basis of student population (Study 1 = secondary, Study 2 = primary). Schools were matched on the basis of number of students and were allocated to receiving the intervention immediately or having a waiting list period. Study 1 had one waiting list period of one school term, creating two steps in the stepped-wedge design (i.e. 3 schools were provided with "Girls on the Go!" each term over 2 terms). Study 2 had two waiting list periods of one and two school terms, creating three steps in the stepped-wedge design (i.e. 2 schools were provided with "Girls on the Go!" each term over 3 terms). Primary outcome measures were self-esteem and impairment inducted by eating disorders. There is a lack of preventative interventions currently available that address low self-esteem, low self-efficacy and body dissatisfaction in young women. This project will be the first group-based, professional-led, targeted program conducted outside the school environment amongst school age young women to be evaluated via a randomised control trial. These findings will indicate if the "Girls on the Go!" program may be successfully used and applied in a culturally diverse environment and with young women of all shapes and sizes. (ACTRN12610000513011).


HOAc catalyzed three-component reaction for the synthesis of 3,3'-(arylmethylene)bis(1H-indoles).
An efficient HOAc catalyzed three-component reaction of 2-(arylethynyl)anilines with arylaldehydes has been achieved, which leads to the generation of 3,3'-(arylmethylene)bis(1H-indoles) with good to excellent yields and high regioselectivity under transition-metal-free conditions. Four new C-C and C-N bonds were effectively formed in a one-pot procedure. Subsequent research on the reaction mechanism indicated that the reaction likely involved the processes of intramolecular cyclization and cascade intermolecular dehydration condensation.


Effectiveness and Safety of Pulsed Radiofrequency Treatment Guided by Computed Tomography for Refractory Neuralgia of Infraorbital Nerve: A Pilot Study.
There is no truly optimal treatment to cure refractory neuralgia of the infraorbital nerve. Recently, nondestructive pulsed radiofrequency (PRF) has become one of the most attractive interventional techniques for painful disorders. However, use of the technique for infraorbital neuralgia has been seldom reported. The purpose of this prospective study is to observe the effectiveness and safety of PRF treatment for neuralgia of the infraorbital nerve. Prospective case series clinical outcome study. University Medical Center, Beijing, China. From January 2011 to November 2012, 36 consecutive patients, following ineffective conservative therapy, underwent PRF treatment and completed 2-year follow-up. Numeric rating scales (NRS), effective rate, additional carbamazepine dosage, and side effects were recorded at postoperative day one, week one, week 2, month one, month 3, month 6, year one, and year 2. Patients were divided into effective group and ineffective group based on postoperative one -month total pain relief or more than 50% reduction in NRS and patients were satisfied with the effect, and possible factors affecting efficacy were compared between the 2 groups. Effective rates were 69%, 69%, 64%, 50%, and 50% at postoperative month one, month 3, month 6, year one, and year 2, respectively. No serious side effects were observed, except that 9 patients felt short-term (one -month duration) mild numbness. Output voltage and tissue resistance in the effective group were significantly higher than the ineffective group (P < 0.01). Intraoperative output voltage was negatively correlated with postoperative one -month NRS (r = -0.332, P < 0.05). The non-controlled and single-centered design of the study. Results demonstrated PRF treatment under computed tomography (CT) guidance for infraorbital neuralgia is safe, effective, and is expected to become an alternative for patients experiencing ineffective conservative therapy. Increasing the output voltage of PRF could be the chosen method to improve the efficacy.


Droplet-microfluidics-assisted sequencing of HIV proviruses and their integration sites in cells from people on antiretroviral therapy.
The human immunodeficiency virus (HIV) integrates its genome into that of infected cells and may enter an inactive state of reversible latency that cannot be targeted using antiretroviral therapy. Sequencing such a provirus and the adjacent host junctions in individual cells may elucidate the mechanisms of the persistence of infected cells, but this is difficult owing to the 150-million-fold higher amount of background human DNA. Here we show that full-length proviruses connected to their contiguous HIV-host DNA junctions can be assembled via a high-throughput microfluidic assay where droplet-based whole-genome amplification of HIV DNA in its native context is followed by a polymerase chain reaction (PCR) to tag droplets containing proviruses for sequencing. We assayed infected cells from people with HIV receiving suppressive antiretroviral therapy, resulting in the detection and sequencing of paired proviral genomes and integration sites, 90% of which were not recovered by commonly used nested-PCR methods. The sequencing of individual proviral genomes with their integration sites could improve the genetic analysis of persistent HIV-infected cell reservoirs.


The role of the fecal stream in Crohn's disease: an historical and analytic review.
Since 1939, a series of clinical reports and laboratory investigations have suggested that the intestinal fecal stream may play a significant part in the pathogenesis of Crohn's disease (CD). The beneficial effect of exclusion of the stream by ileostomy was followed by improvement in patients with CD of the ileum and colon despite little change in the histopathology of the excluded loop, even to the point of allowing restoration of intestinal continuity in some patients. End ileostomy lowers the risk of recurrence of CD compared with anastomotic operations. Ileostomy effluent can reactivate the clinical activity of quiescent bypassed bowel and some of its biochemical processes, and may be related to an ultrafilterable constituent > 5 microns. Experimental models of inflammatory bowel disorders in immunologically altered rodents (transgenic, knockout, or spontaneous) require the presence of normal luminal bacteria, especially of the Bacteroides species, and respond to antibiotic (metronidazole) therapy. Thus, many but not all of the well-recognized clinical features of CD are compatible with a pathogenetic role of the fecal stream. Although difficult to quantitate, this concept opens the way to a variety of testable research lines, and allows some speculation regarding its clinical implications.


Development of a primary cell model derived from porcine dorsal soft palate for foot-and-mouth disease virus research and diagnosis.
Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals that has a significant socio-economic impact. One concern associated with this disease is the ability of its etiological agent, the FMD virus (FMDV), to persist in its hosts through underlying mechanisms that remain to be elucidated. While persistence has been described in cattle and small ruminants, it is unlikely to occur in pigs. One of the factors limiting the progress in understanding FMDV persistence and, in particular, differential persistence is the lack of suitable in vitro models. A primary bovine cell model derived from the dorsal soft palate, which is the primary site of replication and persistence of FMDV in cattle, has been developed, and it seemed relevant to develop a similar porcine model. Cells from two sites of FMDV replication in pigs, namely, the dorsal soft palate and the oropharyngeal tonsils, were isolated and cultured. The epithelial character of the cells from the dorsal soft palate was then assessed by immunofluorescence. The FMDV-sensitivity of these cells was assessed after monolayer infection with FMDV O/FRA/1/2001 Clone 2.2. These cells were also grown in multilayers at the air-liquid interface to mimic a stratified epithelium susceptible to FMDV infection. Consistent with what has been shown in vivo in pigs, our study showed no evidence of persistence of FMDV in either the monolayer or multilayer model, with no infectious virus detected 28 days after infection. The development of such a model opens up new possibilities for the study and diagnosis of FMDV in porcine cells.


DNA microarrays in herbal drug research.
Natural products are gaining increased applications in drug discovery and development. Being chemically diverse they are able to modulate several targets simultaneously in a complex system. Analysis of gene expression becomes necessary for better understanding of molecular mechanisms. Conventional strategies for expression profiling are optimized for single gene analysis. DNA microarrays serve as suitable high throughput tool for simultaneous analysis of multiple genes. Major practical applicability of DNA microarrays remains in DNA mutation and polymorphism analysis. This review highlights applications of DNA microarrays in pharmacodynamics, pharmacogenomics, toxicogenomics and quality control of herbal drugs and extracts.


Fly artifact documentation of Chrysomya megacephala (Fabricius) (Diptera: Calliphoridae) - a forensically important blowfly species in Malaysia.
Analysis on fly artifacts produced by forensically important blowfly, Chrysomya megacephala (Fabricius) (Diptera:Calliphoridae), revealed several unique patterns. They can be divided into fecal spots, regurgitation spots and swiping stains. The characteristics of fecal spots are round with three distinct levels of pigmentation; creamy, brownish and darkly pigmented. Matrix of the spots appears cloudy. The round spots are symmetrical and non-symmetrical, delineated by irregular and darker perimeter which only visible in fairly colored fecal spots. Diameter of these artifacts ranged from 0.5 mm to 4 mm. Vomit or regurgitation spots are determined by the presence of craters due to sucking activity of blowflies and surrounded by thickly raised and darker colored perimeter. The size of these specks ranged from 1 mm to 2 mm. Matrix of the spots displays irregular surface and reflective under auxiliary microscope light. Swiping stains due to defecation by flies consists of two distinguishable segments, the body and tail. It can be seen as a tear drop-like, sperm-like, snake-like and irregular tadpole-like stain. The direction of body and tail is inconsistent and length ranged between 4.8 mm to 9.2 mm. A finding that should be highlighted in this observation is the presence of crater on tadpole-like swiping stain which is apparent by its raised border characteristic and reflective under auxiliary microscope light. The directionality of this darkly brown stain is random. This unique mix of regurgitation and swiping stain has never been reported before. Highlighting the features of artifacts produced by flies would hopefully add our understanding in differentiating them from blood spatters produced from victims at crime scenes.


Interferon alpha induces protein kinase C-epsilon (PKC-epsilon) gene expression and a 4.7-kb PKC-epsilon-related transcript.
Protein kinases play key roles in the induction by human interferon alpha (IFN-alpha) of specific gene expression and biological activity in various human cell lines. We now report that IFN-alpha increased the 7-kb transcript for the epsilon isotype of protein kinase C (PKC-epsilon) and the cellular content of PKC-epsilon 24 and 48 hr after IFN-alpha addition (a 2-fold and 6-fold increase, respectively). Furthermore, IFN-alpha markedly induced a 4.7-kb transcript that hybridized to a PKC-epsilon-specific, but not to a PKC-eta-specific, cDNA probe. The induction of the 4.7-kb PKC-epsilon-related mRNA by IFN-alpha had the following properties reported for the classical IFN-alpha-stimulated genes: rapid kinetics of induction, high maintained levels in IFN-alpha-sensitive but not in IFN-alpha-resistant cell lines, protein synthesis-independent induction, and high sensitivity to inhibitors of protein tyrosine kinase activity. These results show that the regulation of gene expression by IFN-alpha include not only the classical IFN-alpha-stimulated genes but also the coordinated regulation of two PKC-epsilon-related transcripts that appeared to be highly relevant to the biological actions of IFN-alpha.


Mpox: Keep it on the differential.
In its current global outbreak, mpox has exhibited several novel clinical presentations that clinicians should be aware of so they can recognize it if they see it. Although the case rate has decreased, mpox could linger at a low rate or resurface in other populations and thus should remain in the differential diagnosis in patients presenting with potential infections after intimate encounters.


Does nasal septal deviation influence adult posterior choanal size?
Despite the development of modern imaging techniques, no study has been carried out to establish the normal size (particularly the area) of the adult posterior choanae. In this study we present our findings of the normal anatomical sizes of the adult posterior choanae and its relationship to septal deviation, by analysing MRI images of 70 patients. Coronal sections through the sphenoid rostrum and axial sections through the nasal septum were used. There were 32 males and 38 female patients. The age ranged between 18 and 73 years (mean 35.6). Our results show that the posterior choanal dimensions were as follows: right area: 1.35-6.1 cm2 (mean 2.7 cm2); left area: 1.4-5.9 cm2 (mean 2.7 cm2); right width: 0.9-2.1 cm (mean 1.5 cm); left width: 0.9-2.2 cm (mean 1.5 cm); right height: 2.5-4.0 cm (mean 2.6 cm); and left height: 1.5-4.0 cm (mean 2.5 cm). Chi-square analysis showed no statistically significant differences between left- and right-sided measurements. Twenty-three patients had a deviated septum towards the left side, 22 patients towards the right side, and 25 patients had no septal deviation. Chi-square analysis showed no statistical correlation between deviation of the nasal septum and any of the three dimensions of the posterior choanae studied.


The biopsychosocial model of treatment the patients with inflammatory chronic bowel disease.
We present the organised psychological group interventions for persons with inflammatory bowel disease (ulcerose colitis, Morbus Crohn). The actual bio-psychosocial model of health and illness is used to explain the situation of chronically ill patient as stressful life position and their ways of coping with such, health-related problems. Considering that numerous psychological factors can lead to insufficient illness adaptation and (non) adherence to treatment--and all those--to much more complications and higher use of therapies, we try to develop for group of those patients effective model of treatment. The group of 15 gastroenterological patients from treatment in UKC Maribor was included in the psycho-diagnostic procedure (semi-structural interview, The Freiburg's Personal Inventory, The Coping Inventory for Stressful Situations, Health-related Questionnaire of Quality of Life). The data that we had been gathered were significant to the C-type of coping, found in some other group of chronically ill patients, too. For such persons is typically their low emotions expressiveness, especially negative emotions (sadness, anger). In interpersonal contacts they usually show extreme social agreement and low level of assertiveness. So we formed our therapeutic model and its therapeutic aims to the course of being able to express the emotions, to reach higher personal autonomy, better assertively and self image--which at the end have all greater influence on the human's quality of life. After therapeutic model and aims of treatment has been formed, patients with inflammatory bowel disease were treated in cognitive-behavioural group, where also C. Roger's conditions for successful psychotherapy were taken in account and were the part of hole, integrative form of treatment.


Women voicing their autonomy: the changing picture of women's health care.
In recent years women's health concerns have received considerable attention. Both women and the medical establishment have recognized how biases of the past have affected clinical decision making and research affecting women's health. This article explores potential responses to these deficiencies. It suggests that training for health professionals that helps them become more attentive to patient's concerns and respectful of their autonomy will benefit all patients, regardless of gender. In addition, research that focuses upon women's health will benefit all of society.


Cloning and functional characterization of Δ6 fatty acid desaturase (FADS2) in Eurasian perch (Perca fluviatilis).
The Eurasian perch (Perca fluviatilis) is a freshwater carnivorous species of high interest to diversify inland aquaculture. However, little is known about its ability to bioconvert polyunsaturated fatty acids (PUFAs) from plant oils into long chain polyunsaturated fatty acids (LC-PUFAs). In this study, special attention has been given to the fatty acid desaturase 2 (FADS2) which is commonly described to be a rate-limiting enzyme of the LC-PUFA biosynthesis. This work reports on the cloning, tissue expression and functional characterization of the Eurasian perch fads2, but also on the cloning of two alternative splicing transcripts named fads2-AS1 and fads2-AS2. The fads2 cDNA cloned is composed of an open reading frame (ORF) of 1338 nucleotides (nt) and encodes a protein of 445 amino acids. This deduced amino acid sequence displays the typical structure of microsomal FADS2 including two transmembrane domains and an N-terminal cytochrome b5 domain with the "HPGG" motif. Quantitative real-time PCR assay of fads2, fads2-AS1 and fads2-AS2 expressions revealed that the fads2 transcript was mainly expressed in the liver and intestine and exhibited a typical gene expression pattern of freshwater species while fads2-AS1 and fads2-AS2 genes were highly expressed in the brain, followed by the liver and intestine. Functional characterization of Eurasian perch FADS2 in transgenic yeast showed a fully functional Δ6 desaturation activity toward C18 PUFA substrates, without residual Δ5 and Δ8 desaturase activities.


Metabolic syndrome in normal and complicated pregnancies.
The aim of our study was to elucidate the association of the metabolic syndrome with the risk of unsuccessful pregnancy. This was a retrospective observational study conducted at Markusovszky Teaching Hospital, Szombathely, Hungary, a tertiary health care center. During the study period of 2007-2011 (5 years), 7373 pregnancies were followed. Pregnant women who were suffering from metabolic syndrome in the first trimester of gestation during the study period were compared to all other pregnant women without the syndrome. Retrospectively, 219 (2.9%) patients met the criteria of metabolic syndrome during the first trimester. Our goal was to evaluate the prevalence of the metabolic syndrome in normal pregnancies and in those complicated by either premature birth, or intrauterine growth retardation (IUGR), pregnancy-induced hypertension, and preeclampsia. The rate of preterm birth was 15.2% [32/219 in the metabolic syndrome group vs. 11.1% (p=0.051) in the control group]. Within the affected group, 40 pregnancies were complicated with IUGR (18.4%) versus 3.3%, in the unaffected group (p<0.001). In 58 cases, we observed preeclampsia during pregnancy [26.7% vs. 5.2% (p<0.001)] in the control group. Among the patients affected by the metabolic syndrome, 83 patients (38.2%) had more then one pregnancy complication during pregnancy, and only 59 cases (27.2%) had no adverse events during pregnancy and delivery (p<0.001). Our study demonstrated a higher rate of complicated pregnancies in association with metabolic syndrome compared to the control group.


Deep brain stimulation of the ventralis intermedius nucleus for the treatment of essential tremor.
A 59-year-old woman with a 30-year history of essential tremor refractory to medical therapy underwent staged deep brain stimulation of the ventralis intermedius nucleus of the thalamus (VIM). Left-sided lead placement was performed first. Once in the operating room, microelectrode recording (MER) was performed to confirm the appropriate trajectory and identify the VIM border with the ventralis caudalis nucleus. MER was repeated after repositioning 2 mm anteriorly to reduce the likelihood of stimulation-induced paresthesias. Physical examination prior to permanent lead placement demonstrated micro-lesion effect, suggesting optimal trajectory. After implantation of the permanent lead, physical examination showed excellent results. The video can be found here: https://youtu.be/nn3KRdmRCZ4 .


16 beta-[18F]fluoromoxestrol: a potent, metabolically stable positron emission tomography imaging agent for estrogen receptor positive human breast tumors.
16 beta-[18F]Fluoromoxestrol (beta FMOX, 1) is a highly selective, metabolically stable estrogen with potential as a receptor imaging agent. It demonstrates receptor-mediated uptake in the immature rat in the estrogen receptor-rich primary target tissues, uterus and ovaries, as well as, in receptor-poor secondary target tissues, muscle, thymus and kidneys; uptake in the uterus is nearly four times that of the clinically useful 16 alpha-[18F]fluoroestradiol (FES), most likely due to the extended lifetime of the labeled beta FMOX in the blood afforded by its relatively slow metabolism. In vivo and in vitro studies demonstrate a nearly four-fold decrease in metabolism rate between beta FMOX and FES. Dosimetry studies indicate radiation absorbed doses comparable to FES. beta FMOX possesses desirable imaging characteristics and may prove to be a clinically useful imaging agent.


Crystal structure of the human alkaline sphingomyelinase provides insights into substrate recognition.
Absorption of dietary sphingomyelin (SM) requires its initial degradation into ceramide, a process catalyzed by the intestinal enzyme alkaline sphingomyelinase (alk-SMase, NPP7, ENPP7). alk-SMase belongs to the nucleotide pyrophosphatase/phosphodiesterase (NPP) family, the members of which hydrolyze nucleoside phosphates, phospholipids, and other related molecules. NPP7 is the only paralog that can cleave SM, and its activity requires the presence of bile salts, a class of physiological anionic detergents. To elucidate the mechanism of substrate recognition, we determined the crystal structure of human alk-SMase in complex with phosphocholine, a reaction product. Although the overall fold and catalytic center are conserved relative to other NPPs, alk-SMase recognizes the choline moiety of its substrates via an NPP7-specific aromatic box composed of tyrosine residues. Mutational analysis and enzymatic activity assays identified features on the surface of the protein-a cationic patch and a unique hydrophobic loop-that are essential for accessing SM in bile salt micelles. These results shed new light on substrate specificity determinants within the NPP enzyme family.


Merging photoredox and nickel catalysis: decarboxylative cross-coupling of carboxylic acids with vinyl halides.
Decarboxylative cross-coupling of alkyl carboxylic acids with vinyl halides has been accomplished through the synergistic merger of photoredox and nickel catalysis. This new methodology has been successfully applied to a variety of α-oxy and α-amino acids, as well as simple hydrocarbon-substituted acids. Diverse vinyl iodides and bromides give rise to vinylation products in high efficiency under mild, operationally simple reaction conditions.


The argument from potential: a reappraisal.
Several criticisms of the argument from potential are reported. It is noted that such criticisms are inspired by two similarly wrong interpretations of potentiality, one confusing it with possibility and another with probability. A brief analysis of the original Aristotelian context in which the concept emerged shows that potentiality cannot be thought of as indicating the provision of some empirical facts in the future, but must rather be referred to the inherent ontological structure of the being in question. It is then argued that such an Aristotelian concept can be useful to express the dynamic structure of the person, as it must be understood according to contemporary phenomenological personalism. In the light of this philosophical tradition, the embryo can be viewed as a being already possessing the human nature and actively developing its potential for personhood: it also follows that human nature must not be understood as a static and predetermined essence, but rather as the principle of becoming and movement toward further achievements.


The feasibility study of the octane-enhancing process: isobutylene dimerization using C4 mixture.
The dimerization of isobutylene to diisobutylene in C4 mixture was evaluated using various catalysts such as nickel salts system, zeolite system and acidic ion exchange resin. There were shown that the strong acidic type ion exchange resin (Amberlyst 15) under 6 kg/cm2 and 60 degrees C gave rise to 90% conversion and more than 60% selectivity to diisobutylene with acceptable amounts of oligomer as a best catalyst. Therefore, Amberlyst 15 was employed to investigate the optimum reaction condition. In the batch reaction, since the catalyst activity was increased with the increasing reaction temperature, the reaction time should be shortened appropriately to prevent a high yield of oligomer. The reaction rate was increased by the increased amount of catalyst without much change in the product composition. The formation of oligomer was inhibited when a small amount of organic solvents (methyl tert-butyl ether) are attended. In the fixed-bed study, the results indicate that the increase in reaction temperature was accompanied by the increase in reaction rate, however, the selectivity to the dimer was affected. Higher WHSV will enhance the selectivity but reduce the conversion. Conclusively, the appropriate reaction condition was 45 degrees C with WHSV of 10.


Red sea floor origin: rare-Earth evidence.
Abundance patterns of rare earths of submarine tholeiitic basalts from the axial trough of the Red Sea resemble those of basalts from mid-ocean ridges but are distinct from shield or plateau basalts of tholeiitic composition. These results imply that à similar magmatic process, related to spreading of sea floors, operates beneath the axial trough of the Red Sea and the crest of mid-ocean ridges.


Fatty acids and lipid mediators in inflammatory bowel disease: from mechanism to treatment.
Inflammatory Bowel Disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract. Though the pathogenesis of IBD remains unclear, diet is increasingly recognized as a pivotal factor influencing its onset and progression. Fatty acids, essential components of dietary lipids, play diverse roles in IBD, ranging from anti-inflammatory and immune-regulatory functions to gut-microbiota modulation and barrier maintenance. Short-chain fatty acids (SCFAs), products of indigestible dietary fiber fermentation by gut microbiota, have strong anti-inflammatory properties and are seen as key protective factors against IBD. Among long-chain fatty acids, saturated fatty acids, trans fatty acids, and ω-6 polyunsaturated fatty acids exhibit pro-inflammatory effects, while oleic acid and ω-3 polyunsaturated fatty acids display anti-inflammatory actions. Lipid mediators derived from polyunsaturated fatty acids serve as bioactive molecules, influencing immune cell functions and offering both pro-inflammatory and anti-inflammatory benefits. Recent research has also highlighted the potential of medium- and very long-chain fatty acids in modulating inflammation, mucosal barriers, and gut microbiota in IBD. Given these insights, dietary intervention and supplementation with short-chain fatty acids are emerging as potential therapeutic strategies for IBD. This review elucidates the impact of various fatty acids and lipid mediators on IBD and delves into potential therapeutic avenues stemming from these compounds.


Internal validation of STRmix™ - A multi laboratory response to PCAST.
We report a large compilation of the internal validations of the probabilistic genotyping software STRmix™. Thirty one laboratories contributed data resulting in 2825 mixtures comprising three to six donors and a wide range of multiplex, equipment, mixture proportions and templates. Previously reported trends in the LR were confirmed including less discriminatory LRs occurring both for donors and non-donors at low template (for the donor in question) and at high contributor number. We were unable to isolate an effect of allelic sharing. Any apparent effect appears to be largely confounded with increased contributor number.


[AN ABSCESS OF CORPUS SPONGIOSUM CAUSED BY CANDIDURIA: A CASE REPORT].
An 88-year-old man was treated with a urethral bougie after balloon dilation for urethral stricture in 2019. In December 2020, the patient was referred to our hospital with a fever and voiding disturbance. The patient was diagnosed with a urinary tract infection at the time of admission and was treated with an antibacterial agent. Candia glabrata was detected in both the blood and urine cultures obtained on admission. However, antifungal therapy was not administered because the blood culture was negative on reexamination. Sixteen days after admission, magnetic resonance imaging revealed an abscess in the corpus spongiosum. Cystostomy and abscess drainage were performed because the corpus spongiosum abscess was worsening. Candia glabrata was detected in the abscess; therefore, we treated the patient with antifungal therapy. After 14 days of antifungal agent treatment, the corpus spongiosum abscess disappeared. An abscess of the corpus spongiosum caused by candiduria is exceedingly rare; this is the first reported case in Japan.


A Cationic Polymer That Shows High Antifungal Activity against Diverse Human Pathogens.
Invasive fungal diseases are generally difficult to treat and often fatal. The therapeutic agents available to treat fungi are limited, and there is a critical need for new agents to combat these deadly infections. Antifungal compound development has been hindered by the challenge of creating agents that are highly active against fungal pathogens but not toxic to the host. Host defense peptides (HDPs) are produced by eukaryotes as a component of the innate immune response to pathogens and have served as inspiration for the development of many new antibacterial compounds. HDP mimics, however, have largely failed to exhibit potent and selective antifungal activity. Here, we present an HDP-like nylon-3 copolymer that is effective against diverse fungi while displaying only mild to moderate toxicity toward mammalian cells. This polymer is active on its own and in synergy with existing antifungal drugs against multiple species of Candida and Cryptococcus, reaching levels of efficacy comparable to those of the clinical agents amphotericin B and fluconazole in some cases. In addition, the polymer acts synergistically with azoles against different species of Aspergillus, including some azole-resistant strains. These findings indicate that nylon-3 polymers are a promising lead for development of new antifungal therapeutic strategies.


Evaluation of Clinical Compendia Used for Medicare Part D Coverage Determinations for Off-label Prescribing in Dermatology.
When making coverage determinations for off-label prescribing, Medicare Part D recognizes 2 compendia: the American Hospital Formulary Service (AHFS) Drug Information and the DRUGDEX Information System. Deficiencies in the accuracy and completeness of these compendia could result in coverage denials for necessary, effective, evidence-based treatments. To evaluate these compendia for dermatologic conditions, with a focus on less common conditions that often require systemic treatment. This cross-sectional study was conducted from July 1, 2018, through September 30, 2018. To identify diseases for which dermatologists may often need access to off-label systemic treatments, a list of 22 chronic, noninfectious, nonneoplastic diseases with at least 4 systemic therapies (including 1 in the first-line therapies and less than 25% approved by the US Food and Drug Administration) were selected for evaluation. With use of Treatment of Skin Disease, 5th Edition, a list of first-, second-, and third-line medications was created, including the level of evidence for each disease. A search of AHFS and DRUGDEX compendia was performed to evaluate for inclusion of the evidence-based therapies. In addition, the references cited in the compendia to justify inclusion of the therapy were examined qualitatively. Percentage of treatment options included in each compendium, stratified by level of evidence and position on the therapeutic ladder. Concordance between the 2 compendia was assessed using Cohen κ. Overall, 73 of 238 treatments (30.7%) evaluated were included in either compendium. Among individual diseases, 10 of 22 (45%) had 1 or fewer treatments included in the DRUGDEX compendium and 15 of 22 (68%) had 1 or fewer treatments included in the AHFS compendium. Discrepancies in which a medication was included in one compendium but not in the other compendium occurred for 53 of the 238 medications (22.3%) evaluated. Literature use did not follow a discernible pattern and was often based on decades-old sources. The findings suggest that treatment options listed in these compendia are incomplete, outdated, idiosyncratic, and unpredictable. To ensure that patients can access treatments for their disease, it appears that policies to reduce the reliance on these compendia for coverage determinations should be developed.


The effects of RGD (Arg-Gly-Asp) peptides on glaucoma filtration surgery in rabbits.
Integrins are the main mediators of the interaction between fibroblasts and extracellular matrix (ECM) during scar formation. The adhesion motive RGD (Arg-Gly-Asp) is contained in the ECM and is recognized by the integrin receptor. Soluble peptides containing the RGD sequence can compete with -RGD- contained in the ECM for binding to the integrin receptor and thus prevent cell adhesion and scar formation. The peptides RGD (p602), GRGDSP (p603), GRGDSPCA (p604), and GGRGDSPCA (p605) were used in 25 glaucoma filtering surgeries in rabbits (five eyes per peptide and five with saline). Postoperative subconjunctival injections of peptides were given at days 0, 4, 8, 12, and 16. Bleb size, bleb survival, and signs of toxicity were examined. The GRGDSPCA and GGRGDSPCA showed an increase in bleb formation, size, and survival with no clinical signs of toxicity compared with controls (P < .008). Histopathologic evaluation confirmed inhibitory effects in scar formation with bleb formation, and transmission electron microscopy demonstrated that there was no toxicity to the ciliary body. These peptides were effective in controlling scar formation in glaucoma filtering surgery.


Prognostic factors in infiltrating lobular carcinoma.
Various prognostic factors viz. clinical details, histologic features including subtypes, elastosis, desmoplasia, in situ carcinoma, perineural and vascular invasion, Nottingham Prognostic Index (NPI), and menopausal status were evaluated in Infiltrating Lobular carcinoma (ILC) in the context of patient survival. 138 patients had presented with ILC over a period of 20 years. Histological subtypes of ILC and vascular invasion played a role in the biologic behaviour of the tumour. Interestingly premenopausal status protected against the risk for relapse, while being postmenopausal, increased the risk. NPI was demonstrated as an independent significant prognostic factor and was a good predictor for relapse. This study underlines the role of the pathologist in determination of the prognostic groups in Infiltrating lobular carcinoma.


Using genetic variation to optimize nutritional preemption.
One of the promises of nutritional genomics is a set of dietary recommendations that leverage our understanding of nutrient-gene interaction in the preemptive dietary management of complex chronic diseases. Whether nutritional genomics can deliver on this promise is a matter of debate and controversy. Although nutritional genomics is often viewed as an extension of pharmacogenomics, the pharmacogenomics paradigm is a disease-centric reductionistic model that overshadows both the complexities and opportunities to be leveraged in preemptive nutritional pharmacology. Moreover, the pharmacogenomics model tends to set clinical expectations that nutritional genomics may not be able to achieve. The biological boundaries of nutritional pharmacology are being tested in many areas of preventive medicine such as cardiovascular disease and cancer. In this regard, the lessons learned in one disease may be germane to the other. Recent results from the Vitamin Intervention for Stroke Prevention (VISP), the Norwegian Vitamin (NORVIT), and the Heart Outcomes Prevention Evaluation (HOPE) 2 trials underscore the incertitude of translating epidemiologic data into preemptive nutritional guidance. Moving ahead, the genetic determinism of the nutrigenomic model needs to take on a more holistic and phenotypic focus. To the extent this can be done, preemptive nutrition may one day become a safe and practical reality.