Considerations for minimally invasive gynecologic surgery in obese patients.
The purpose is to review the key anatomical and physiological changes in obese patients and their effects on preoperative, intraoperative, and postoperative care and to highlight the best practices to safely extend minimally invasive approaches to obese patients and provide optimal surgical outcomes in this high-risk population. Minimally invasive surgery is safe, feasible, and cost-effective for obese patients. Obesity is associated with anatomical and physiological changes in almost all organ systems, which necessitates a multimodal approach and an experienced, multidisciplinary team. Preoperative counseling, evaluation, and optimization of medical comorbidities are critical. The optimal minimally invasive approach is primarily determined by the patient's anatomy and pathology. Specific intraoperative techniques and modifications exist to maximize surgical exposure and panniculus management. Postoperatively, comprehensive medical management can help prevent common complications in obese patients, including hypoxemia, venous thromboembolism, acute kidney injury, hyperglycemia, and prolonged hospitalization. Given significantly improved patient outcomes, minimally invasive approaches to gynecological surgery should be considered for all obese patients with particular attention given to specific perioperative considerations and appropriate referral to an experienced minimally invasive surgeon.


Congenital osteolipoma associated with cleft palate: a case report.
Congenital tumors of the oral cavity are uncommon. Teratoid tumors account for most of the reported cases and are infrequently associated with a cleft of the soft palate. Of the remaining tumors associated with pediatric cleft palate, congenital lipoma is rare. Lipomas of the oral cavity may show cartilaginous or osseous changes. These changes have not been reported in lipoma associated with cleft palate. A rare case of congenital osteolipoma associated with cleft palate and showing osseous change is presented here. The pathogenesis of the lesion and the osseous metaplasia are described. The present case is the second case of congenital lipoma associated with cleft palate in the literature.


A metropolitan experience with infrainguinal revascularization. Operative risk and late results in northeastern Ohio.
Despite being of fundamental importance, the late results of major arterial reconstruction rarely have been documented throughout a large metropolitan area. In this study of 932 patients entered into the computer registry of the Cleveland Vascular Society, 19 surgeons representing 13 community hospitals and referral centers in Cleveland and Akron report the intermediate-term outcome during a mean interval of 35 months after infrainguinal lower extremity revascularization performed in northeastern Ohio from 1978 through 1982. Operative risk (5%), the early amputation rate (7%), and actuarial 5-year survival (48% to 55%) for patients with rest pain or tissue necrosis were significantly worse (p less than 0.05) than comparable figures (0.6%, 0%, and 77%, respectively) for others who underwent procedures for disabling claudication. Although both materials had similar success above the knee, the cumulative 3-year patency rate of autogenous vein bypass to the distal popliteal (69% to 88%; p less than 0.05) and tibioperoneal arteries (43%; 0.05 less than p less than 0.1) was superior to the results of polytetrafluoroethylene grafts (32% to 50% and 19%, respectively). Moreover, polytetrafluoroethylene grafts required reoperations at three times the rate of vein grafts to maintain limb salvage.


Synthesis and properties of 5-cyano-substituted nucleoside analog with a donor-donor-acceptor hydrogen-bonding pattern.
6-Aminopyridin-2-ones form Watson-Crick pairs with complementary purine analogues to add a third nucleobase pair to DNA and RNA, if an electron-withdrawing group at position 5 slows oxidation and epimerization. In previous work with a nucleoside analogue trivially named dZ, the electron withdrawing unit was a nitro group. Here, we describe an analogue of dZ (cyano-dZ) having a cyano group instead of a nitro group, including its synthesis, pK(a), rates of acid-catalyzed epimerization, and enzymatic incorporation.


TLR-TRIF pathway enhances the expression of KSHV replication and transcription activator.
Kaposi's sarcoma-associated herpesvirus (KSHV) is a human γ-herpesvirus. KSHV replication and transcription activator (RTA) is necessary and sufficient for KSHV reactivation from latency. Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns, act through adaptors, and initiate innate and adaptive immune responses against pathogens. Toll/interleukin-1-receptor domain containing adaptor protein inducing interferon-β (TRIF) is an adaptor associated with TLR3 and TLR4 signaling, and is closely related to antiviral signaling to activate type I interferon (IFN) production. We previously found that KSHV RTA degrades TRIF indirectly and blocks TLR3 pathways. In this report, we find that TRIF, as well as TLR3 activation, enhances KSHV RTA protein expression. The C-terminal region of the RTA is involved in the responding TRIF-mediated enhancement. The degradation of TRIF and the enhancement of RTA expression are using two different pathways. The enhancement by TLR-TRIF is at least partially via promoting translational efficiency of RTA mRNA. Finally, the receptor-interacting protein 1 (RIP1) may be involved in TRIF-mediated enhancement of RTA expression, but not in the RTA-mediated degradation of TRIF. Therefore, the activation of TLR-TRIF pathway enhances KSHV RTA protein expression, and KSHV RTA in turn degrades TRIF to block innate immunity. The putative KSHV-TLR-adaptor-interacting loop may be a critical element to evade and usurp host innate immunity in KSHV life-cycle.


Structural evidence for ammonia tunneling across the (beta alpha)(8) barrel of the imidazole glycerol phosphate synthase bienzyme complex.
Since reactive ammonia is not available under physiological conditions, glutamine is used as a source for the incorporation of nitrogen in a number of metabolic pathway intermediates. The heterodimeric ImGP synthase that links histidine and purine biosynthesis belongs to the family of glutamine amidotransferases in which the glutaminase activity is coupled with a subsequent synthase activity specific for each member of the enzyme family. Its X-ray structure from the hyperthermophile Thermotoga maritima shows that the glutaminase subunit is associated with the N-terminal face of the (beta alpha)(8) barrel cyclase subunit. The complex reveals a putative tunnel for the transfer of ammonia over a distance of 25 A. Although ammonia tunneling has been reported for glutamine amidotransferases, the ImGP synthase has evolved a novel mechanism, which extends the known functional properties of the versatile (beta alpha)(8) barrel fold.


Light microscopic visualization of peroxisomes and plasmalogens in first trimester chorionic villi.
Peroxisomes and their metabolites the plasmalogens were visualized in chorionic villi by quick and simple procedures. Villi were stained and mounted in toto, and can also be embedded. These methods may contribute to early prenatal diagnosis of peroxisomal disorders (Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum's disease a.o.).


Collagen II-pulsed antigen-presenting cells genetically modified to secrete IL-4 down-regulate collagen-induced arthritis.
We explored the possibility that pulsed antigen-presenting cells (APC) provide a model vector system for site-specific delivery of immunosuppressive proteins during collagen-induced arthritis (CIA), an animal model for rheumatoid arthritis. Thus, mice were treated with either B cells or macrophages engineered to secrete IL-4 and loaded (or not) with type II collagen (CII). Systemic injection of an IL-4-producing B cell hybridoma resulted in a reduction of arthritis severity which was further improved when APC were incubated with CII before their transfer. Unmanipulated B cells loaded with CII also exerted a potent suppressive effect. Likely, clinical amelioration was observed in mice given at priming syngeneic bone marrow-derived macrophages producing IL-4 and pulsed with CII in comparison to the other groups. When the same dose of cells was transferred at disease onset, a moderate beneficial effect was observed. Whatever the APC inoculated, the beneficial effect did not rely upon an IL-4-driven shift towards Th2 phenotype. Systemic administration of fluorescent dye labeled macrophages to arthritic mice has shown that some of these cells rapidly migrate to joints. Moreover, IL-4 transfected macrophages retained their potent capacity to present CII peptides to T cells. These findings validate the use of CII peptide-loaded engineered APC as therapeutic vector cells in CIA and allow consideration of this strategy for the administration of various anti-inflammatory proteins.


Characteristics and outcome of 90 cases of fetal omphalocele.
The aim of this study was to describe the outcome of a case series of fetuses with omphalocele. Ninety fetuses with omphalocele at the National Center for Fetal Medicine (NCFM) between January 1985 and January 2004 were followed from the time of prenatal diagnosis. Follow-up times ranged from 6 months to 17 years. Omphaloceles were subdivided into epigastric, central and hypogastric types based on their location on the abdominal wall. There were 58 central and 32 epigastric omphaloceles. Abnormal karyotype was found in 40/58 (69%) of the central and in 4/32 (12.5%) of the epigastric omphaloceles. Trisomy 18 was the most frequent abnormality associated with omphalocele. Among the fetuses with normal karyotype, 89% of the central and 71% of the epigastric cases had other anomalies. 38 (66%) of the fetuses with central omphalocele were terminated and 12 (21%) died during pregnancy or after delivery. 11 (34%) of the fetuses with epigastric omphalocele were terminated and eight (25%) died during pregnancy or after delivery. Of the 90 cases followed from the time of diagnosis there were 21 (23%) survivals. Of eight survivals with central omphalocele, only two were considered healthy while six had other anomalies and/or substantially impaired development. Of 13 survivals with epigastric omphalocele, six were considered healthy and seven had other anomalies and/or substantial impairment. Fetal central and epigastric omphaloceles may be different entities: central omphaloceles are more strongly associated with abnormal karyotype (69%) than are epigastric omphaloceles (12.5%). The outcome of fetuses with omphalocele is poor irrespective of the type of omphalocele, with only eight of the 90 (9%) being alive and healthy at present. The results emphasize the importance of identifying both those fetuses with a potentially good prognosis and favorable outcome and those which are likely to have a fatal outcome.


Distribution and stability of [111In]bleomycin and its fractions in tumor-bearing mice.
The tissue distributions in glioma-bearing mice given injections of [111In]bleomycin (BLM) indicated that tumor concentrations and ratios of tumor to blood, muscle and brain for [111In]BLM-B2 and -A2 were higher than those for unfractionated [111In]BLM. Autoradiographs of electrophoretic gels of urine containing [111In]BLM or one of its fractions differed from those containing 111InCl3. [111In]BLM and its fractions (A2 and B2) were found to be stable in vivo. The fractions may be more useful in the clinic than [111In]BLM.


Structural mechanism of R2D2 and Loqs-PD synergistic modulation on DmDcr-2 oligomers.
Small interference RNAs are the key components of RNA interference, a conserved RNA silencing or viral defense mechanism in many eukaryotes. In Drosophila melanogaster, Dicer-2 (DmDcr-2)-mediated RNAi pathway plays important roles in defending against viral infections and protecting genome integrity. During the maturation of siRNAs, two cofactors can regulate DmDcr-2's functions: Loqs-PD that is required for dsRNA processing, and R2D2 that is essential for the subsequent loading of siRNAs into effector Ago2 to form RISC complexes. However, due to the lack of structural information, it is still unclear whether R2D2 and Loqs-PD affect the functions of DmDcr-2 simultaneously. Here we present several cryo-EM structures of DmDcr-2/R2D2/Loqs-PD complex bound to dsRNAs with various lengths by the Helicase domain. These structures revealed that R2D2 and Loqs-PD can bind to different regions of DmDcr-2 without interfering with each other. Furthermore, the cryo-EM results demonstrate that these complexes can form large oligomers and assemble into fibers. The formation and depolymerization of these oligomers are associated with ATP hydrolysis. These findings provide insights into the structural mechanism of DmDcr-2 and its cofactors during siRNA processing.


Structural and functional investigation of the intermolecular interaction between NRPS adenylation and carrier protein domains.
Nonribosomal peptide synthetases (NRPSs) are modular proteins that produce peptide antibiotics and siderophores. These enzymes act as catalytic assembly lines where substrates, covalently bound to integrated carrier domains, are delivered to adjacent catalytic domains. The carrier domains are initially loaded by adenylation domains, which use two distinct conformations to catalyze sequentially the adenylation of the substrate and the thioesterification of the pantetheine cofactor. We have used a mechanism-based inhibitor to determine the crystal structure of an engineered adenylation-carrier domain protein illustrating the intermolecular interaction between the adenylation and carrier domains. This structure enabled directed mutations to improve the interaction between nonnative partner proteins. Comparison with prior NRPS adenylation domain structures provides insights into the assembly line dynamics of these modular enzymes.


Prenatal diagnosis of trisomy 21, 18 and 13 by quantitative pyrosequencing of segmental duplications.
Chromosomal aberration mostly occurs in chromosomes 21, 18 and 13, with an incidence approximately 1 out of 160 live births in humans, therefore making prenatal diagnosis necessary in clinics. Current methods have drawbacks such as time consuming, high cost, complicated operations and low sensitivity. In this paper, a novel method for rapid and accurate prenatal diagnosis of aneuploidy is proposed based on pyrosequencing, which quantitatively detects the peak height ratio (PHR) of different bases of segmental duplication. A direct polymerase chain reaction (PCR) approach was undertaken, where a small volume of amniotic fluid was used as the starting material without DNA extraction. Single-stranded DNA was prepared from PCR products and subsequently analyzed using pyrosequencing. The PHR between target and reference chromosome of 2.2 for euploid and 3:2 for a trisomy fetus were used as reference. The reference intervals and z scores were calculated for discrimination of aneuploidy. A total of 132 samples were collected, within trisomy 21 (n = 11), trisomy 18 (n = 3), trisomy 13 (n = 2), and unaffected controls (n = 116). A set of six segmental duplications were chosen for analysis. This method had consistent results with karyotyping analysis, a correct diagnosis with 100% sensitivity and 99.9% specificity.


Association between endometriosis and polymorphisms in insulin-like growth factor binding protein genes in Korean women.
Genetic factors are known to be associated with the development and progression of endometriosis, but the genes related to endometriosis have not been defined. Insulin-like growth factor binding proteins (IGFBPs) are believed to be involved in the proliferation and apoptosis of cells that play an important role in the pathophysiologic mechanism of endometriosis. This study aimed to determine the association between endometriosis and polymorphisms of the IGFBP genes in Korean women. In a case-control study, the rs1995051, rs1065780 and c.759A>G single nucleotide polymorphisms (SNPs) in the IGFBP1 gene and the -672A>G, -202A>C and c.95C>G SNPs in the IGFBP3 gene were analyzed in 128 women with endometriosis and 108 normal control women. The haplotype genotype composed of a combination of three IGFBP1 gene polymorphisms was not related to endometriosis, while the haplotype genotype of the IGFBP3 gene had a significant association with endometriosis. Women not carrying the AAG (-672A/-202A/c.95G) haplotype allele of three IGFBP3 gene polymorphisms have a 3.19-times higher risk of endometriosis compared with women with AAG homozygotes, and this trend was found in women with advanced endometriosis but not in women with early endometriosis. The AAG haplotype allele of the -672A>G, -202A>C and c.95C>G polymorphisms in the IGFBP3 gene may be associated with advanced endometriosis in Korean women.


Intercellular gap junctions in the developing retina and pigment epithelium of the chick.
Gap junctions are found in the pigment epithelium, between retina and pigment epithelium and in the retina of 5-14 day chick embryos, they are identified using block staining and extracellular tracer techniques. In the pigment epithelium gap junctions are found between cell bodies and interdigitating processes and many change their position during development. Gap junctions between retina and pigment epithelium are only made by undifferentiated retinal ventricular cells and may provide intercytoplasmic pathways important for photoreceptor differentiation. Retinal gap junctions are found in an outer zone next to the pigment epithelium and inner zone near the vitreous, they are only seen between ventricular cells but may provide pathways for ganglion cell specification. The role of gap junctions in the generation of retinal neurons is discussed.


Oxidative stress: The core pathogenesis and mechanism of Alzheimer's disease.
As the number of patients with Alzheimer's disease (AD) increases, it brings great suffering to their families and causes a heavy socioeconomic burden to society. A vast amount of funds and a mass of research have been devoted to elucidating the pathology of AD. However, the main pathogenesis is still elusive, and its mechanism is not completely clear. Research on the mechanisms of AD mainly focuses on the amyloid cascade, tau protein, neuroinflammation, metal ions, and oxidative stress hypotheses. Oxidative stress is as a bridge that connects the different hypotheses and mechanisms of AD. It is a process that causes neuronal damage and occurs in various pathways. Oxidative stress plays a critical role in AD and can even be considered a crucial central factor in the pathogenesis of AD. Previous reviews have also summarized the role of oxidative stress in AD, but these mainly review a specific signaling pathway. Taking oxidative stress as the central point, this review comprehensively expands on the roles of oxidative stress that are involved in the pathogenesis of AD. The vivid and easy-to-understand figures systematically clarify the connected roles of oxidative stress in AD and allow readers to further understand oxidative stress and AD.


A unified model for binocular fusion and depth perception.
We describe a new unified model to explain both binocular fusion and depth perception, over a broad range of depths. At each location, the model consists of an array of paired spatial frequency filters, with different relative horizontal shifts (position disparity) and interocular phase disparities of 0, 90, ±180, or -90°. The paired filters with different spatial profiles (non-zero phase disparity) compute interocular misalignment and provide phase-disparity energy (binocular fusion energy) to drive selection of the appropriate filters along the position disparity space until the misalignment is eliminated and sensory fusion is achieved locally. The paired filters with identical spatial profiles (0 phase disparity) compute the position-disparity energy. After sensory fusion, the combination of position and possible residual phase disparity energies is calculated for binocular depth perception. Binocular fusion occurs at multiple scales following a coarse-to-fine process. At a given location, the apparent depth is the weighted sum of fusion shifts combined with residual phase disparity in all spatial-frequency channels, and the weights depend on stimulus spatial frequency and stimulus contrast. To test the theory, we measured disparity minimum and maximum thresholds (Dmin and Dmax) at three spatial frequencies and with different intraocular contrast levels. The stimuli were Random-Gabor-Patch (RGP) stereograms consisting of Gabor patches with random positions and phases, but with a fixed spatial frequency. The two eyes viewed identical arrays of patches except that one eye's array could be shifted horizontally and could differ in contrast. Our experiments and modeling reveal two contrast normalization mechanisms: (1) Energy Normalization (EN): Binocular energy is normalized with monocular energy after the site of binocular combination. This predicts constant Dmin thresholds when varying stimulus contrast in the two eyes; (2) DSKL model Interocular interactions: Monocular contrasts are normalized before the binocular combination site through interocular contrast gain-control and gain-enhancement mechanisms. This predicts contrast dependent Dmax thresholds. We tested a range of models and found that a model consisting of a second-order pathway with DSKL interocular interactions and a first-order pathway with EN at each spatial-frequency band can account for both the Dmin and Dmax data very well. Simulations show that the model makes reasonable predictions of suprathreshold depth perception.


Analysis of the three Yersinia pestis CRISPR loci provides new tools for phylogenetic studies and possibly for the investigation of ancient DNA.
The precise nature of the pathogen having caused early plague pandemics is uncertain. Although Yersinia pestis is a likely candidate for all three plague pandemics, the very rare direct evidence that can be deduced from ancient DNA (aDNA) analysis is controversial. Moreover, which of the three biovars, Antiqua, Medievalis or Orientalis, was associated with these pandemics is still debated. There is a need for phylogenetic analysis performed on Y. pestis strains isolated from countries from which plague probably arose and is still endemic. In addition there exist technical difficulties inherent to aDNA investigations and a lack of appropriate genetic targets. The recently described CRISPRs (clustered regularly interspaced short palindromic repeats) may represent such a target. CRISPR loci consist of a succession of highly conserved regions separated by specific "spacers" usually of viral origin. To be of use, data describing the mechanisms of evolution and diversity of CRISPRs in Y. pestis, its closest neighbors, and other species which might contaminate ancient DNA, are necessary. The investigation of closely related Y. pestis isolates has revealed recent mutation events in which elements constituting CRISPRs were acquired or lost, providing essential insight on their evolution. Rules deduced represent the basis for subsequent interpretation. In the present study, the CRISPR loci from representative Y. pestis and Yersinia pseudotuberculosis strains were investigated by PCR amplification and sequence analysis. The investigation of this wider panel of strains, including other subspecies or ecotypes within Y. pestis and also Y. pseudotuberculosis strains provides a database of the existing CRISPR spacers and helps predict the expected CRISPR structure of the Y. pestis ancestor. This knowledge will open the way to the development of a spoligotyping assay, in which spacers can be amplified even from highly degraded DNA samples. The data obtained show that CRISPR analysis can provide a very powerful typing tool, adapted to the systematic, large-scale genotyping of Y. pestis isolates, and the creation of international typing databases. In addition, CRISPRs do constitute a very promising new tool and genetic target to investigate ancient DNA. The corresponding genetic targets are small (<70bp), present in multiple copies (usually more than 10), highly conserved and specific. In addition, the assay can be run in any laboratory. Interpretation of the data is not dependent on accurate sequence data.


Bacteriocin production by spray-dried lactic acid bacteria.
Cell survival and antagonistic activity against Listeria innocua, Listeria monocytogenes and Staphylococcus aureus were investigated after spray-drying three bacteriocin-producing strains of lactic acid bacteria: Carnobacterium divergens, Lactobacillus salivarius and Lactobacillus sakei. Bacterial cell concentrates were spray-dried and stored at 4 degrees C and 18 degrees C and 0.3% ERH (equilibrium relative humidity). Enumeration and antagonistic activity were evaluated before and after spray-drying and at regular intervals during storage. A higher survival rate was obtained when survival was performed at 4 degrees C. With the exception of Carnobacterium divergens which lost the inhibitory activity against Staph. aureus after drying, antagonistic production was not affected by the process nor by the storage. Of the three species studied, Lact. salivarius showed the highest resistance to the spray-drying and storage processes. Spray-drying is a potentially useful process for large scale production of dried powders containing viable organisms with antagonistic activity against pathogens.


A highly sensitive assay for spectrofluorimetric determination of reduced glutathione using organic nano-probes.
In this study, the new nanometer-sized fluorescent particles (1-pyrenemethylamine nanoparticles) have been prepared by reprecipitation method under ultrasonic radiation. These nanoparticles have the potential to overcome problems encountered by organic small molecules by combining the advantages of high photobleaching threshold, high quantum yield, long fluorescence lifetime, good chemical stability, and wide excitation spectral properties. These nanoparticles will be able to be directly used as fluorescent nanoparticles probe without modification. A new fluorimetric method for the determination of reduced glutathione (GSH) has been developed with these nanoparticles. Under optimal conditions, the organic nanoparticles reacted with GSH and o-phthalaldehyde (OPA) to give a highly fluorescent derivative in Na2CO3-HCl buffer (pH=9.0). The fluorescence excitation and emission wavelengths of fluorescent derivative were located at 345 and 400 nm, respectively. The relative fluorescence intensity (RF) was linear in the range of the GSH concentration from 8.0x10(-7) to 1.1x10(-4)moll(-1). Limit of detection of 7.1x10(-8)moll(-1) was achieved for the reduced glutathione. The method was validated and applied to the analysis of three synthetic samples containing reduced glutathione.


Synthesis and anticancer activity of novel spiro-isoxazoline and spiro-isoxazolidine derivatives of α-santonin.
In the present study, novel spiro derivatives of α-santonin were prepared and tested for their anticancer activity against a panel of six human cancer cell lines. Spiro-isoxazoline and spiro-isoxazolidine derivatives have been generated on C-ring of α-santonin (α-methylene-γ-butyrolactone) by the 1,3-dipolar cycloaddition of α-santonin derivative 6 with nitrile oxides 7 and nitrones 9 respectively. Among all, compound 10b″ had shown IC50 of 0.01, 0.5 and 0.3 μM against PC-3, THP-1 and MCF-7 cell lines respectively. Further, flow cytometry studies showed that PC-3 cells treated with the spiro-isoxazolidine derivative 10b″ were arrested in the sub G1 phase of the cell cycle in a concentration dependent manner. The spiro-isoxazolidine derivative 10b″ also showed concentration dependent inhibitory activity against NF-κB, p65 with 57% inhibition in 24 h at 10 μM.


Screening, brief interventions, referral to treatment (SBIRT) for illicit drug and alcohol use at multiple healthcare sites: comparison at intake and 6 months later.
Alcohol screening and brief interventions in medical settings can significantly reduce alcohol use. Corresponding data for illicit drug use is sparse. A Federally funded screening, brief interventions, referral to treatment (SBIRT) service program, the largest of its kind to date, was initiated by the Substance Abuse and Mental Health Services Administration (SAMHSA) in a wide variety of medical settings. We compared illicit drug use at intake and 6 months after drug screening and interventions were administered. SBIRT services were implemented in a range of medical settings across six states. A diverse patient population (Alaska Natives, American Indians, African-Americans, Caucasians, Hispanics), was screened and offered score-based progressive levels of intervention (brief intervention, brief treatment, referral to specialty treatment). In this secondary analysis of the SBIRT service program, drug use data was compared at intake and at a 6-month follow-up, in a sample of a randomly selected population (10%) that screened positive at baseline. Of 459,599 patients screened, 22.7% screened positive for a spectrum of use (risky/problematic, abuse/addiction). The majority were recommended for a brief intervention (15.9%), with a smaller percentage recommended for brief treatment (3.2%) or referral to specialty treatment (3.7%). Among those reporting baseline illicit drug use, rates of drug use at 6-month follow-up (4 of 6 sites), were 67.7% lower (p<0.001) and heavy alcohol use was 38.6% lower (p<0.001), with comparable findings across sites, gender, race/ethnic, age subgroups. Among persons recommended for brief treatment or referral to specialty treatment, self-reported improvements in general health (p<0.001), mental health (p<0.001), employment (p<0.001), housing status (p<0.001), and criminal behavior (p<0.001) were found. SBIRT was feasible to implement and the self-reported patient status at 6 months indicated significant improvements over baseline, for illicit drug use and heavy alcohol use, with functional domains improved, across a range of health care settings and a range of patients.


Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine.
The host response to biomaterials has been studied for decades. Largely, the interaction of host immune cells, macrophages in particular, with implanted materials has been considered to be a precursor to granulation tissue formation, the classic foreign body reaction, and eventual encapsulation with associated negative impacts upon device functionality. However, more recently, it has been shown that macrophages, depending upon context dependent polarization profiles, are capable of affecting both detrimental and beneficial outcomes in a number of disease processes and in tissue remodeling following injury. Herein, the diverse roles played by macrophages in these processes are discussed in addition to the potential manipulation of macrophage effector mechanisms as a strategy for promoting site-appropriate and constructive tissue remodeling as opposed to deleterious persistent inflammation and scar tissue formation.


Neurodegenerative diseases-Caps: a capsule network based early screening system for the classification of neurodegenerative diseases.
The two most generally diagnosed Neurodegenerative diseases are the Alzheimer and Parkinson diseases. So this paper presents a fully automated early screening system based on the Capsule network for the classification of these two Neurodegenerative diseases. In this study, we hypothesized that the Neurodegenerative diseases-Caps system based on the Capsule network architecture accurately performs the multiclass i.e. three class classification into either the Alzheimer class or Parkinson class or Healthy control and delivers better results in comparison other deep transfer learning models. The real motivation behind choosing the capsule network architecture is its more resilient nature towards the affine transformations as well as rotational & translational invariance, which commonly persists in the medical image datasets. Apart from this, the capsule networks overcomes the pooling layers related deficiencies from which conventional CNNs are mostly affected and unable to delivers accurate results especially in the tasks related to image classification. The various Computer aided systems based on machine learning for the classification of brain tumors and other types of cancers are already available. Whereas for the classification of Neurodegenerative diseases, the amount of research done is very limited and the number of persons suffering from this type of diseases are increasing especially in developing countries like India, China etc. So there is a need to develop an early screening system for the correct multiclass classification into Alzheimer's, Parkinson's and Normal or Healthy control cases. The Alzheimer disease and Parkinson progression (ADPP) dataset is used in this research study for the training of the proposed Neurodegenerative diseases-Caps system. This ADPP dataset is developed with the aid of both the Parkinson's Progression Markers Initiative (PPMI) and Alzheimer's disease Neuroimaging Initiative (ADNI) databases. There is no such early screening system exist yet, which can perform the accurate classification of these two Neurodegenerative diseases. For the sake of genuine comparison, other popular deep transfer learning models like VGG19, VGG16, ResNet50 and InceptionV3 are implemented and also trained over the same ADPP dataset. The proposed Neurodegenerative diseases-Caps system deliver accuracies of 97.81, 98, 96.81% for the Alzheimer, Parkinson and Healthy control or Normal cases with 70/30 (training/validation split) and performs way better as compare to the other popular Deep transfer learning models. The online version contains supplementary material available at 10.1007/s11571-022-09787-1.


The datasets of factors influencing adoption of electric Cars in Malaysia: A structural equation modelling (SEM) analysis.
The datasets designated in this article were obtained as a result of 10 months of data collection, carried out between august 2017 and May 2018 in Kuala Lumpur, Malaysia. The aim of study was to evaluate the factors Influencing adoption of battery electric vehicles (BEVs) in Malaysia. The data were collected from University Technology Malaysia (Kuala Lumpur campus) and five different companies in Kuala Lumpur. A total of 500 questionnaires were distributed and 322 questionnaires were obtained. After data screening, 312 datasets were analysed. Respondents of the study were postgraduate students, university lecturers and top to low level managers.


Transient cardiac failure due to Takotsubo cardiomyopathy after surgical reduction of nasal fracture.
Takotsubo syndrome, also known as ampulla cardiomyopathy, broken heart syndrome, idiopathic apical ballooning syndrome, and stress-induced myocardial stunning, has been first described by Japanese authors in 1996 and subsequently specified in 2001; it derives from the resemblance between the ancient round-bottomed, narrow-necked Japanese fishing pots used to trap octopus in Asia and the end-systolic appearance of the left ventricle on ventriculography. We introduce the case of a woman who was involved in a traffic car crash and, subsequently, was admitted to the Maxillo-Facial Unit of the Novara Major Hospital with a diagnosis of nasal fracture. She underwent general anesthesia for the reduction of the fracture; after surgery, she developed acute chest pain, elevated cardiac biomarkers, ischemic electrocardiogram changes, and transient akinesis of the left ventricle without significant epicardial coronary artery disease. A diagnosis of takotsubo syndrome was made. This syndrome, which presents the same clinical features of a ventricular failure, is probably underdiagnosed, but after the introduction of sophisticated cardiac imaging and coronary intervention, more cases are identified and an unnecessary thrombolytic therapy can be spared. This reversible condition, which is, to our knowledge, never mentioned after a craniomaxillofacial surgical procedure, should be considered in the diagnostic algorithm for all patients presenting with acute onset of chest pain, elevated cardiac biomarkers, and ischemic changes on the electrocardiogram after a general anesthesia.


Spatio-temporal evolution of eutrophication and water quality in the Turawa dam reservoir, Poland.
The objectives of the article are: to assess spatio-temporal evolution of eutrophication and water quality of the Turawa dam reservoir, located in south-western Poland on the Mała Panew River; to identify location and relationship between potential sources of physicochemical pollution related to the progressing process of eutrophication; and to determine trophic status and water quality indices of the selected research object. The analysis (Mann-Whitney U test, PCA, HCA, Spearman correlation matrix) showed a high susceptibility of the reservoir to eutrophication processes, especially due to the influence of dangerous loads of compounds emerging from areas with high tourist intensity and pollutants flowing from the Mała Panew River. The parameters deteriorating the ecological status were TP, DO, BOD5, and COD. Considering the cumulative results of water quality indices for the period 1998-2020, the average water quality was in classes II or III. A noticeable deterioration appeared in water quality for the years 2016-2020, which proves the progressing eutrophication in the Turawa reservoir. In 1998-2020, the reservoir was classified as eutrophic or mesoeutrophic based on the calculated three trophic status indices. This article would help in developing a strategy for dealing with water blooms, a reliable system for monitoring pressures causing eutrophication, and optimal technologies for the reconstruction of multifunctional reservoirs.


Two cases of acute anterolateral compartment syndrome following inversion ankle injuries.
Compartment syndrome is a limb threatening, and sometimes life-threatening medical condition. It usually occurs in high energy lower extremity injuries, commonly in the younger patient with classic signs and symptoms. Pain out of proportion to exam is one of the key elements in diagnosis. A high vigilance for signs and symptoms of this condition should be present on most physicians' radars who treat emergency conditions, as this case report demonstrates, the mechanism and story are not always classic. Two cases of young, healthy adults who underwent fasciotomy for compartment release for compartment syndrome isolated to the anterolateral compartment, but who did not sustain a high energy trauma, but rather a twisting ankle injury. Compartment syndrome can occur in young, healthy, active patients with a lower energy twisting injury and without fracture. A high level of suspicion on the clinicians' part will prevent adverse outcomes to the patient.


Structurally- and dynamically-driven allostery of the chymotrypsin-like proteases of SARS, Dengue and Zika viruses.
Coronavirus 3C-like and Flavivirus NS2B-NS3 proteases utilize the chymotrypsin fold to harbor their catalytic machineries but also contain additional domains/co-factors. Over the past decade, we aimed to decipher how the extra domains/co-factors mediate the catalytic machineries of SARS 3C-like, Dengue and Zika NS2B-NS3 proteases by characterizing their folding, structures, dynamics and inhibition with NMR, X-ray crystallography and MD simulations, and the results revealed: 1) the chymotrypsin fold of the SARS 3C-like protease can independently fold, while, by contrast, those of Dengue and Zika proteases lack the intrinsic capacity to fold without co-factors. 2) Mutations on the extra domain of SARS 3C-like protease can transform the active catalytic machinery into the inactive collapsed state by structurally-driven allostery. 3) Amazingly, even without detectable structural changes, mutations on the extra domain are sufficient to either inactivate or enhance the catalytic machinery of SARS 3C-like protease by dynamically-driven allostery. 4) Global networks of correlated motions have been identified: for SARS 3C-like protease, N214A inactivates the catalytic machinery by decoupling the network, while STI/A and STIF/A enhance by altering the patterns of the network. The global networks of Dengue and Zika proteases are coordinated by their NS2B-cofactors. 5) Natural products were identified to allosterically inhibit Zika and Dengue proteases through binding a pocket on the back of the active site. Therefore, by introducing extra domains/cofactors, nature develops diverse strategies to regulate the catalytic machinery embedded on the chymotrypsin fold through folding, structurally- and dynamically-driven allostery, all of which might be exploited to develop antiviral drugs.


Usability Evaluation of An Electronic Medication Administration Record (eMAR) Application.
Electronic medication administration records (eMARs) have been widely used in recent years. However, formal usability evaluations are not yet available for these vendor applications, especially from the perspective of nurses, the largest group of eMAR users. To conduct a formal usability evaluation of an implemented eMAR. Four evaluators examined a commercial vendor eMAR using heuristic evaluation techniques. The evaluators defined seven tasks typical of eMAR use and independently evaluated the application. Consensus techniques were used to obtain 100% agreement of identified usability problems and severity ratings. Findings were reviewed with 5 clinical staff nurses and the Director of Clinical Informatics who verified findings with a small group of clinical nurses. Evaluators found 60 usability problems categorized into 233 heuristic violations. Match, Error, and Visibility heuristics were the most frequently violated. Administer Medication and Order and Modify Medications tasks had the highest number of heuristic violations and usability problems rated as major or catastrophic. The high number of usability problems could impact the effectiveness, efficiency and satisfaction of nurses' medication administration activities and may include concerns about patient safety. Usability is a joint responsibility between sites and vendors. We offer a call to action for usability evaluations at all sites and eMAR application redesign as necessary to improve the user experience and promote patient safety.


The effects of isoproterenol on intracellular calcium concentration.
beta-Adrenergic agonist, isoproterenol (ISO), is a potent relaxant of tracheal smooth muscle and inhibits carbachol-induced contraction. The effect of ISO on intracellular free Ca2+ concentration ([Ca2+]i) was examined in bovine tracheal smooth muscle strips, employing aequorin as Ca2+ indicator. Surprisingly, 10 microM ISO induces a 5-fold increase in [Ca2+]i which then gradually declines but still remains higher than basal after 1 h of stimulation. The ISO-induced increase in [Ca2+]i is dose-dependent, and the ED50 is approximately 50 nM. The ISO-induced increase in [Ca2+]i is inhibited by a beta-receptor blocker, propranolol, not by an alpha-blocker, phentolamine. The ISO-induced rise in [Ca2+]i is dependent on extracellular Ca2+. Forskolin, an adenylate cyclase activator, and vasoactive intestinal peptide, which is known to stimulate adenylate cyclase via a specific receptor in this tissue, have similar effects on [Ca2+]i, suggesting that a rise in cyclic AMP concentration mediates this effect of ISO on [Ca2+]i. Pretreatment of muscle with 10 microM ISO inhibits both the initial Ca2+ transient and the contractile response induced by 0.3 microM carbachol. Conversely, in carbachol-pretreated muscle strips, addition of ISO causes a fall rather than a rise in [Ca2+]i, and an inhibition of contraction. These results indicate that ISO has effects on cellular Ca2+ metabolism at more than a single site in bovine tracheal smooth muscle, that these effects are different in control and carbachol-pretreated muscle, and that the relaxing effect of ISO is not due solely to its effect on Ca2+ metabolism.


Changes in lipids and free fatty acid fractions in adult Haemonchus contortus during incubation in vitro.
Adult Haemonchus contortus (Rud., 1803) has been investigated for its ability to utilize lipids with regard to the total lipids, sterols, free fatty acids, acylglycerols and phospholipids produced during incubation in vitro. All these components exhibit extensive fluctuations, decreasing at some times and increasing at others, thus indicating both biosynthesis and utilization. Also, changes in fatty acid components of total lipids have been analyzed by gas liquid chromatography. These observations indicate that H. contortus is capable of utilizing 16:0, 18:0, 18:1, 18:2, 20:0, 20:un1, 20:un2, 21:0, 21:un1, 21:1, 21:un2, 22:un1, 22:3, 22:?, 22:un2 and 24:3 fatty acids. At the same time, because of large increases in 15:0, 16:0, 18:0, 18:?, 18:1, 18:2, 20:0, 20:un1, 20:un2, 21:0, 21:un1, 21:1 and 21:un2 acids, it is postulated that these acids are synthesized by adult H. contortus.


The use of CAM in a New Zealand-based general practice: a multiple case-study.
To explore the factors which underpin the healthcare consumers' decision-making to use CAM in the primary setting. An explorative, multiple case-study of seven convenience-sampled participants where in-depth, semi-structured interviews were employed. The findings showed that participants would continue to utilise CAM, even where CAM had no scientific evidence. The participants believed that CAM should be integrated into mainstream healthcare service delivery. There are few international studies that have reported on the utilisation and prevalence of CAM within the General Practice (GP) or clinic setting. The reasons why clients select specific CAM therapies, where they are offered in these settings, remain unclear. This study, however, casts further light on this matter.


[Granular cell tumor of the larynx: a case report].
Granular cell tumors are benign subcutaneous or submucosal lesions of neurogenic origin. They are quite commonly found in the head and neck region, particularly in the tongue. However, only about 200 cases of laryngeal granular cell tumors have been reported so far. Most laryngeal granular cell tumors are located in the posterior part of the vocal fold and in the posterior commissure. Differentiation from inflammatory as well as from malignant lesions is possible only by biopsy. The treatment of choice is complete excision. However, tumor extension and expected morbidity of the surgery will inevitably influence the extent of the resection. Recurrences after complete excision are rare.


Staged surgical repair for extensive cardiovascular damage by syphilis.
A 45-year-old man had aortic regurgitation with a syphilitic true aneurysm of the ascending to transverse arch aorta and a descending aortic aneurysm from chronic Stanford type B aortic dissection. After antibiotic therapy, two-staged surgical repair was performed and there has been no evidence of recurrence in 12 months since the second stage. We describe the successful management of extensive cardiovascular syphilitic damage.


Umbilical cord blood and peripheral blood-derived regulatory T cells therapy: Progress in type 1 diabetes.
Regulatory T cells (Tregs) are key regulators for the inflammatory response and play a role in maintaining the immune tolerance. Type 1 diabetes (T1D) is a relatively common autoimmune disease that results from the loss of immune tolerance to β-cell-associated antigens. Preclinical models have demonstrated the safety and efficacy of Tregs given in transplant rejection and autoimmune diseases such as T1D. Adoptive transfer of Tregs has been utilized in clinical trials for over a decade. However, the achievement of the adoptive transfer of Tregs therapy in clinical application remains challenging. In this review, we highlight the characterization of Tregs and compare the differences between umbilical cord blood and adult peripheral blood-derived Tregs. Additionally, we summarize conditional modifications in the expansion of Tregs in clinical trials, especially for the treatment of T1D. Finally, we discuss the existing technical challenges for Tregs in clinical trials for the treatment of T1D.


Microbiota in Rosacea.
Rosacea is a complex facial skin condition associated with abnormal inflammation and vascular dysfunction. Next to the known trigger factors, the role of microbiota in the development and aggravation of rosacea continues to raise interest. Demodex folliculorum mites, Helicobacter pylori, Staphylococcus epidermidis, Chlamydia pneumoniae, and the Demodex-associated bacterium, Bacillus oleronius are microbes that have been linked with rosacea. However, the results of studies which assessed their involvement in the disease have been inconsistent and inconclusive. Microbiological research in many different disciplines exploded in recent years as methods to analyze complex microbial communities at the taxonomic and phylogenetic levels became available. Here, we provide an update on the microorganisms implicated in rosacea and review the potential pathogenic role of microbes in the development of rosacea.


Arthroscopic debridement and drilling of osteochondral lesions of the talus.
Diagnosis of OLTs requires a high index of suspicion because these lesions are rare and the symptoms can be falsely attributed to acute or chronic ankle sprains. When no abnormality is present on plain radiographs, a bone scan or MRI can reliably identify the presence of an OLT. CT scanning can provide even better detail of the location and size of the fragment and help stage these lesions and guide treatment. Arthroscopic staging is believed to be the best method to determine treatment. In a patient without an obvious loose body, initial nonoperative treatment is warranted. When nonoperative therapy fails or when a high stage lesion is present, operative options should be explored. Arthroscopic techniques provide results that are equal to or better than management by arthrotomy and have the advantages of lower morbidity and quicker overall rehabilitation time. In most cases, arthroscopic treatment involves loose body removal and debridement and drilling of the underlying bone or drilling alone for intact lesions. Although it is unknown whether such treatment can reduce the incidence of late arthrosis in a patient who has an OLT, a recent study suggested that healing occurs and the MRI appearance of the talar dome normalizes in many patients postoperatively.


Nuclear protrusions in malignant tumours with large abnormal chromosomes: observations on C-banded preparations.
The appearances are described in 4 human tumours having nuclear protrusions associated with large abnormal chromosomes. In C-banded preparations, chromocentres were seen in the protrusions only where interstitial C-bands were present on the long arm of the abnormal chromosome, providing evidence that the protrusions are indeed formed by the long arms.


A laterally π-expanded fluorone dye as an efficient near infrared fluorophore.
The synthesis and photophysical properties of new dibenzo[b,i]fluorone dye frameworks (BX and FBX) are described. Both BX and FBX display near-infrared sharp absorption and emission upon the addition of base due to the achievement of efficient π-conjugation based on the small bond alternation strategy.


Effects of running water on brainstem lateral line responses in trout, Oncorhynchus mykiss, to sinusoidal wave stimuli.
We investigated how single units in the medial octavolateralis nucleus of the rainbow trout, Oncorhynchus mykiss, respond to a 50-Hz vibrating sphere in still and running water. Four types of units were distinguished. Type MI units ( N=16) were flow-sensitive; their ongoing discharge rates either increased or decreased in running water, and as a consequence, responses of these units to the vibrating sphere were masked if the fish was exposed to water flow. Type MII units ( N=7) were not flow-sensitive; their ongoing discharge rates were comparable in still and running water, and thus their responses to the vibrating sphere were not masked. Type MIII units ( N=7) were also not flow-sensitive; nevertheless, their responses to the vibrating sphere were masked in running water. Type MIV units ( N=14) were flow-sensitive, but their responses to the vibrating sphere were not masked. Our data confirm previous findings in the goldfish, Carassius auratus, indicating that the organization of the peripheral lateral line is reflected to a large degree in the medial octavolateralis nucleus. We compare data from goldfish and trout and discuss differences with respect to lateral line morphology, lifestyle and habitat of these species.


A survey of combined epidural-propofol anesthesia with noninvasive positive pressure ventilation as a minimally invasive anesthetic protocol.
Combined epidural-propofol anesthesia with use of noninvasive positive pressure ventilation (NPPV) via the nose has been used routinely in our operating theaters. The purpose of this report was to present a survey of this anesthesia. 265 adult patients undergoing lower extremity or lower abdominal gynecological surgery during 1999 were examined. After epidural anesthesia, patients were given propofol infusion. NPPV was applied with an inspiratory/expiratory positive airway pressure of 14/8 cm H2O, a respiratory rate of 10 breaths/min, and oxygen delivery into the nasal mask resulting in a concentration of 40% or an inspiratory oxygen fraction of 0.35. Epidural anesthesia was continuously applied after surgery for postoperative pain relief. Various data related to the surgery or anesthesia were evaluated both on the day of surgery and on postoperative day 1. Of 265 patients, 3 patients could not receive our anesthetic protocol. Of the residual 262 patients, no patients showed serious clinical problems during anesthesia, excluding for hypotension, which was observed in 31-56% patients and was treated with ephedrine injection. Patients informed us of good analgesia (98%), feelings (78%) and dreams (47%). On postoperative day 1, postoperative analgesia and mood conditions were satisfactory. There were no patients complaining of intraoperative awareness. The principle of our anesthesia consists of epidural anesthesia, sole propofol infusion and noninvasive airway management, so as to provide an anesthetic technique with minimal invasiveness. Although airway maintenance by NPPV is not always suitable, our anesthesia is practicable for certain kinds of operations.


[Severe hyperthermia and neurological disorders following prostaglandin treatment for uterine atonia after caesarean section].
Uterine atony is the most frequent cause of post-partum haemorrhage. In France, the management is based on early administration of oxytocic agents and prostaglandin analogues (sulprostone-Nalador®). We report the case of a 30-year-old woman who presented soon after administration of sulprostone, a severe hyperthermia with neurological disorders. A complete reversibility was observed a few hours after discontinuation of sulprostone administration. Other causes were eliminated by biological and radiological findings.


Heme catabolism in human kidneys. Effect of various nephritides.
The role of the kidneys in heme metabolism was examined by determining heme oxygenase and biliverdin reductase activities in needle biopsy specimens from the kidneys of 11 female and 14 male patients with different renal diseases. The results show that both enzymes are present in human renal tissue. Our results indicate that heme oxygenase and biliverdin reductase increase slightly with age, but that there is no sex difference. A rising serum creatinine concentration is not reflected in the activity of heme degrading enzymes. Neither do the different types of nephritides, without detectable hemolysis, show significant differences in the renal activities of heme oxygenase and biliverdin reductase. This study thus outlines the basal physiological role of the human kidneys in heme degradation.


Association with mature plants protects seedlings from predation in an arid grassland shrub, Gutierrezia microcephala.
Survivorship of Gutierrezia microcephala (Compositae) seedlings was studied in an undisturbed arid grassland and in experimental plots where various components of the natural vegetation were removed following seed germination. The major causes of seedling mortality were herbivore damage from the specialist grasshopper, Hesperotettix viridis, and drought stress associated with competition from established plants. The relative intensity of these mortality factors varied strongly with seedling size. Large seedlings had higher overall survivorship but were most likely to be killed by defoliation; most small seedlings died of drought stress.In plots where all perennial grasses were removed (leaving established G. microcephala plants), seedling survivorship was 5 times greater than in undisturbed vegetation. Surviorship in plots where both grasses and mature G. microcephala were removed was slightly poorer than in undisturbed vegetation due to a large increase in mortality from defoliation. From May-August, when the herbivore H. viridis was abundant, seedling survivorship was better in the immediate vicinity of mature conspecific plants than in plots lacking mature G. microcephala, both in the presence and absence of perennial grasses. These results provide a counter example to theories predicting that the impact of specialist herbivores on seedling recruitment is greatest in the vicinity of parent plants.


Association of very low prostate-specific antigen levels with increased cancer-specific death in men with high-grade prostate cancer.
The objective of this study was to determine whether a very low presenting prostate-specific antigen (PSA) level was associated with greater prostate cancer-specific mortality (PCSM) among men with a Gleason score (GS) of 8 to 10. The Surveillance, Epidemiology, and End Results program was used to identify 328,904 men diagnosed with clinicalT1 (cT1)-4N0M0 prostate cancer between 2004 and 2010. A multivariate Fine-Gray competing risks regression analysis was used to determine PCSM as a function of the PSA level (≤ 2.5, 2.6-4, 4.1-10, 10.1-20, 20.1-40, or > 40 ng/mL) and GS (8-10 vs ≤ 7). The median follow-up was 38 months. Among men with GS 8-10 disease, with a PSA level of 4.1 to 10 ng/mL as the referent, the adjusted hazard ratio for PCSM for men was 2.15 with a PSA level ≤ 2.5 ng/mL (95% confidence interval [CI], 1.65-2.79; P < .001), 1.60 with a PSA level of 2.6 to 4 ng/mL (95% CI, 1.22-2.10; P = .001), 1.60 with a PSA level of 10.1 to 20 ng/mL (95% CI, 1.41-1.82; P < .001), 2.08 with a PSA level of 20.1 to 40 ng/mL (95% CI, 1.81-2.38; P < .001), and 3.23 with a PSA level > 40 ng/mL (95% CI, 2.85-3.65; P < .001). This suggested a U-shaped distribution. There was a significant interaction between the PSA level and GS (P(interaction) < .001) such that only a PSA level ≤ 2.5 ng/mL significantly predicted poorer PCSM among patients with GS 8-10 disease. Among patients with high-grade disease, patients with PSA levels ≤ 2.5 ng/mL or PSA levels of 2.6 to 4 ng/mL appear to have a higher risk for cancer-specific death in comparison with patients with PSA levels of 10.1 to 20 ng/mL, and this supports the notion that low PSA levels in GS 8-10 disease may be a sign of aggressive and very poorly differentiated or anaplastic low PSA-producing tumors. Patients with low-PSA, GS 8-10 disease should be considered for clinical trials studying the use of chemotherapy and other novel agents for very high-risk prostate cancers.


Central retinal vein occlusion associated with clomiphene-induced ovulation.
To report a case of central retinal vein occlusion associated with clomiphene citrate (CC). Case study. Ophthalmology clinic of an academic hospital. A 36-year-old woman referred from the infertility clinic for blurred vision. Ophthalmic examination after CC therapy. Central retinal vein occlusion after ovulation induction with CC. A 36-year-old Chinese woman developed central retinal vein occlusion after eight courses of CC. A search of the literature on the thromboembolic complications of CC does not include this severe ophthalmic complication, although mild visual disturbance after CC intake is not uncommon. This is the first reported case of central retinal vein occlusion after treatment with CC. Extra caution is warranted in treating infertility patients with CC, and patients should be well informed of this side effect before commencement of therapy.


Blood pressure variability, cardiac baroreflex sensitivity and organ damage in experimentally hypertensive rats.
1. The present study was designed to investigate the haemodynamic features and morphological changes in experimentally hypertensive rat models. 2. Sprague-Dawley rats were used to prepare the experimentally hypertensive models, including two-kidney, one-clip renovascular hypertensive (2K1C) rats, deoxycorticosterone acetate salt hypertensive (DOCA) rats and N(G)-nitro-l-arginine methyl ester-induced hypertensive (l-NAME) rats. Six weeks after the induction of hypertension, 24 h blood pressure was recorded and blood pressure variability (BPV) expressed by 24 h (or 12 h in the daytime and night-time study) standard deviation of the variables was calculated. Then, cardiac baroreflex sensitivity (BRS) was determined and four endogenous factors (tumour necrosis factor-alpha, interleukin-1beta, angiotensin II and endothelin-1) were measured. Finally, morphological changes were examined. 3. It was found that an increase in BPV and a decrease in BRS were accompanied by an elevation of blood pressure in all three hypertensive models. The DOCA rats had the highest BPV, whereas the l-NAME rats had the lowest BRS. 4. Morphological changes were similar in DOCA and l-NAME rats and the cardiac changes were relatively slight in 2K1C rats. Tumour necrosis factor-alpha was increased in all the three models, especially in DOCA rats. Endothelin-1 was higher in DOCA rats and angiotensin II was increased in 2K1C rats and decreased in DOCA rats. 5. In conclusion, increased BPV and decreased BRS accompanied the elevation of blood pressure in all three hypertensive models. The DOCA rats had the highest BPV and the l-NAME rats had the lowest BRS. Obvious organ damage was seen in all three hypertensive models 6 weeks after the induction of hypertension.


Fitness costs of induced resistance: emerging experimental support for a slippery concept.
Fitness costs can explain the evolution and maintenance of induced resistance in plants. However, the methods currently used to gather evidence for such costs do not allow decreases in fitness to be cleanly attributed to individual traits responsible for induced resistance, because the studies are plagued by multiple confounding responses. Reproductive performance provides an overview of physiological performance and is thus a useful currency to understand the function of induced responses. Integrated molecular, physiological and ecological studies are needed to identify the mechanisms responsible for the decrease in fitness and to evaluate fully the usefulness of the cost paradigm.


Hypothalamic- and pituitary-derived growth and reproductive hormones and the control of energy balance in fish.
Most endocrine systems in the body are influenced by the hypothalamic-pituitary axis. Within this axis, the hypothalamus delivers precise signals to the pituitary gland, which in turn releases hormones that directly affect target tissues including the liver, thyroid gland, adrenal glands and gonads. This action modulates the release of additional hormones from the sites of action, regulating key physiological processes, including growth, metabolism, stress and reproduction. Pituitary hormones are released by five distinct hormone-producing cell types: somatotropes (which produce growth hormone), thyrotropes (thyrotropin), corticotropes (adrenocorticotropin), lactotropes (prolactin) and gonadotropes (follicle stimulating hormone and luteinizing hormone), each modulated by specific hypothalamic signals. This careful and distinct organization of the hypothalamo-pituitary axis has been classically associated with the existence of many lineal axes (e.g., the hypothalamic-pituitary-gonadal axis) in charge of the control of the different physiological processes. While this traditional concept is valid, it is becoming apparent that hormones produced by the hypothalamo-pituitary axis have diverse effects. For instance, gonadotropin-releasing hormone II has been associated with a suppressive effect on food intake in fish. Likewise, growth hormone has been shown to influence appetite, swimming activity and aggressive behavior in fish. This review will focus on the hypothalamic and pituitary hormones classically involved in regulating growth and reproduction, and will attempt to provide a general overview of the current knowledge on their actions on energy balance and appetite in fish. It will also give a brief perspective of the role of some of these peptides in integrating feeding, metabolism, growth and reproduction.


Nucleosome "phasing" and cruciform structures in circular supercoiled pBR322 DNA.
Cruciform structures have been detected in pBR322 supercoiled DNA, both in its naked state and when complexed with histone octamer, using S1 endonuclease cleavage and EcoRI restriction. An inspection of the DNA sequence shows that the S1-hypersensitive sites are very near to AT-rich regions of pBR322 genome. A nucleosome "phasing" in these regions, as found on AT-rich regions of SV40 DNA (15), has been shown by restriction enzymes analysis. On the basis of these results it can be proposed that cruciform structures protrude on the nucleosome surface. This model explains the reason why these structures, which need high superhelical density, can exist in supercoiled DNA partially relaxed by nucleosome formation.


Taxes on sugar-sweetened beverages: results from a 2011 national public opinion survey.
Consumption of sugar-sweetened beverages including nondiet sodas, sport drinks, and energy drinks has been linked with obesity. Recent state and local efforts to tax these beverages have been unsuccessful. Enactment will be unlikely without public support, yet little research is available to assess how to effectively make the case for such taxes. The objectives were to assess public opinion about arguments used commonly in tax debates regarding sugar-sweetened beverages and to assess differences in public opinion by respondents' political party affiliation. A public opinion survey was fielded in January-March 2011 using a probability-based sample of respondents from a large, nationally representative online panel to examine public attitudes about nine pro- and eight anti-tax arguments. These data were analyzed in August 2011. Findings indicated greater public agreement with anti- than pro-tax arguments. The most popular anti-tax argument was that a tax on sugar-sweetened beverages is arbitrary because it does not affect consumption of other unhealthy foods (60%). A majority also agreed that such taxes were a quick way for politicians to fill budget holes (58%); an unacceptable intrusion of government into people's lives (53.8%); opposed by most Americans (53%); and harmful to the poor (51%). No pro-tax arguments were endorsed by a majority of the public. Respondents reported highest agreement with the argument that sugar-sweetened beverages were the single largest contributor to obesity (49%) and would raise revenue for obesity prevention (41%). Without bolstering public support for existing pro-tax messages or developing alternative pro-tax messages, enacting such policies will be difficult. Message-framing studies could be useful in identifying promising strategies for persuading Americans that taxes on sugar-sweetened beverages are warranted.


Usefulness of 16S rDNA sequencing for the diagnosis of infective endocarditis caused by Corynebacterium diphtheriae.
We report a rare case of infective endocarditis caused by Corynebacterium diphtheriae in an 8-year-old boy, 2 years after a right ventricular outflow tract reconstruction with a bovine Contegra valved conduit. The patient recovered well after an RV-PA conduit enblock explantation and replacement with an aortic homograft with antibiotic treatment. All bacteriological cultures of excised tissue and blood were negative. The aetiological agent was identified as C. diphtheriae subsp. gravis by 16s rDNA sequencing.


Characterization of the prephenate dehydrogenase-encoding gene, TYR1, from Saccharomyces cerevisiae.
TYR1, the gene from Saccharomyces cerevisiae, which encodes prephenate dehydrogenase, one of the tyrosine biosynthetic enzymes, has been cloned by complementing a yeast tyr1 mutant strain. The DNA fragment containing the gene is part of a 45-kb cosmid clone which represents a region of chromosome II covering the genetically mapped tyr1 locus. The nucleotide sequence of a 3.1-kb region carrying the TYR1 gene and adjacent regions has been determined. The open reading frame contains 441 codons, corresponding to about 52.2 kDa for the encoded protein. The canonical NAD-binding domain is located within the first 45 amino acids of the protein. By primer extension, we show that there is one transcription start point. Presumably, the expression of TYR1 is not under the general GCN4 control. Instead, we find a dependence on the presence or absence of phenylalanine. These data were obtained by analysing CAT activity in constructs containing promoter fragments of TYR1 and the cat reporter gene.


Effects of methionine and/or disaccharide injected in the amnion of geese on post-hatching pectoral muscle and small intestine development, glycogen reserves, jejunum morphology, and digestive enzymes activities.
This study was conducted to investigate the effects of in ovo injection of methionine (Met) and/or disaccharide (DS) on post-hatching pectoral muscle and small intestine development, glycogen reserves, jejunum morphology, and jejunum digestive enzymes activities. A total of 600 fertilized eggs containing live embryo from geese were randomly assigned into 4 groups with 6 replicates and 25 eggs per replicate in a completely randomized design employing a 2 × 2 factorial experiment. Factors in 4 groups included noninjection, Met injection (5 g/L Met + 7.5 g/L NaCl), DS injection (25 g/L maltose + 25 g/L sucrose + 7.5 g/L NaCl), or DS plus Met injection (25 g/L maltose + 25 g/L sucrose + 5 g/L Met + 7.5g/L NaCl), respectively. In ovo nutritional injections were performed at day 23 of incubation, and the experiment until d 21 post-hatching. We found that in ovo feeding of Met increased relative weight of pectoral muscle and small intestine, jejunum alkaline phosphatase activities, and jejunum villus height and surface area. DS injection improved the relative weight of pectoral muscle, pectoral and liver glycogen contents, jejunum villus height, width, and surface area, and jejunum sucrase, Na+/K+ATPase, and alkaline phosphatase activities. In addition, Met plus DS injection synergistically improved jejunum villus height and surface area. Therefore, Met plus DS injection is a suitable strategy for improving intestinal parameters in gosling during post-hatching periods.


Relation of activation-induced deaminase (AID) expression with antibody response to A(H1N1)pdm09 vaccination in HIV-1 infected patients.
The relevance of CD4+T-cells, viral load and age in the immunological response to influenza infection and vaccination in HIV-1 infected individuals has previously been pointed out. Our study aimed at assessing, in the setting of 2009 A(H1N1)pdm09 influenza vaccination, whether quantification of activation-induced deaminase (AID) expression in blood B-cells may provide additional indications for predicting antibody response to vaccination in HIV-1 infected patients with similar CD4+T-cell counts and age. Forty-seven healthy controls, 37 ART-treated and 17 treatment-naïve HIV-1 infected patients were enrolled in the study. Blood was collected prior to A(H1N1)pdm09 vaccination and at 1, 3 and 6 months after vaccination. Antibody titers to A(H1N1)pdm09 vaccine were measured by hemagglutination inhibition (HI) assay while the mRNA expression levels of AID were measured by quantitative real time PCR. Upon B-cell activation in vitro, AID increase correlated to antibody response to the A(H1N1)pdm09 vaccine at 1 month after vaccination in all individuals. In addition, the maximum expression levels of AID were significantly higher in those individuals who still carried protective levels of A(H1N1)pdm09 antibodies after 6 months from vaccination. No correlation was found between CD4+T-cell counts or age at vaccination or HIV-1 viral load and levels of A(H1N1)pdm09 antibodies. Assessing AID expression before vaccination may be an additional useful tool for defining a vaccination strategy in immune-compromised individuals at risk of immunization failure.


Modification of the metabolism and toxicity of styrene and styrene oxide in hepatic cytochrome P450 reductase deficient mice and CYP2F2 deficient mice.
Styrene causes toxicity in both the lung and the liver. The study of the relationship of this toxicity to the metabolism of styrene has been aided by the use of knockout mice for both bioactivation and detoxification pathways. It has been hypothesized that CYP2E1 is primarily responsible for styrene bioactivation in mouse liver and CYP2F2 in mouse lung. Two knockout strains were used in the current studies. Mice deficient in hepatic cytochrome P450 reductase had much less hepatic metabolism of styrene to styrene oxide. Styrene (600 mg/kg, i.p.) caused significant hepatotoxicity, as determined by serum sorbitol dehydrogenase and glutathione levels, in the wild-type but not in the knockout mice. It caused lung toxicity, as determined by protein levels, cell number, and lactate dehydrogenase activity in the bronchioalveolar lavage fluid of wild-type mice, but this effect was less in the knockout mice. In CYP2F2 knockout mice there was only a small decrease in the hepatic metabolism of styrene but a very large decrease in pulmonary metabolism. As expected the CYP2F2 knockout and wild-type mice were equally susceptible to styrene-induced hepatotoxicity, but the knockout mice were less susceptible to styrene-induced pneumotoxicity. Although the results are inconsistent with the simple hypothesis that styrene pneumotoxicity is due to the bioactivation of styrene to styrene oxide by CYYP2F2, they demonstrate the importance of both liver and lung in the metabolism of styrene, but additional pharmacokinetic studies are needed to help clarify the relationship between target organ metabolism and susceptibility.


Epstein-Barr virus-positive blastoid nasal T/natural killer-cell lymphoma in a caucasian.
T/natural killer (NK)-cell lymphoma is a subtype of non-Hodgkin's lymphoma, with frequent cutaneous involvement; it follows an aggressive course. Most cases are reported in Asia, and typically present with nasopharyngeal involvement. There is a distinct variant known as blastoid T/NK-cell lymphoma, which affects elderly, non-Asian patients, with absence of nasal involvement. We report a middle-aged caucasian man who had blastoid T/NK-cell lymphoma with nasal involvement.


Antisaccade performance is abnormal in schizophrenia patients but not in their biological relatives.
Numerous studies have replicated the finding that schizophrenia patients make an increased number of errors on an antisaccade task. Some studies have reported that relatives of schizophrenia patients also make an increased number of antisaccade errors, a finding that has been interpreted to support the usefulness of compromised antisaccade performance as an index of genetic liability for schizophrenia. We examined performance on an antisaccade task in schizophrenia patients, nonpsychiatric controls, first-degree relatives of schizophrenia patients and first-degree relatives of nonpsychiatric controls. Schizophrenia patients made significantly more errors than did nonpsychiatric controls, but relatives of schizophrenia patients did not differ from relatives of controls or from all controls. Increased antisaccade errors on the standard version of the antisaccade task are associated with schizophrenia, but do not seem to be a co-familial trait for schizophrenia.


Novel mutations in PAX6, OTX2 and NDP in anophthalmia, microphthalmia and coloboma.
Anophthalmia and microphthalmia (A/M) are developmental ocular malformations defined as the complete absence or reduction in size of the eye. A/M is a highly heterogeneous disorder with SOX2 and FOXE3 playing major roles in dominant and recessive pedigrees, respectively; however, the majority of cases lack a genetic etiology. We analyzed 28 probands affected with A/M spectrum (without mutations in SOX2/FOXE3) by whole-exome sequencing. Analysis of 83 known A/M factors identified pathogenic/likely pathogenic variants in PAX6, OTX2 and NDP in three patients. A novel heterozygous likely pathogenic variant in PAX6, c.767T>C, p.(Val256Ala), was identified in two brothers with bilateral microphthalmia, coloboma, primary aphakia, iris hypoplasia, sclerocornea and congenital glaucoma; the unaffected mother appears to be a mosaic carrier. While A/M has been reported as a rare feature, this is the first report of congenital primary aphakia in association with PAX6 and the identified allele represents the first variant in the PAX6 homeodomain to be associated with A/M. A novel pathogenic variant in OTX2, c.651delC, p.(Thr218Hisfs*76), in a patient with syndromic bilateral anophthalmia and a hemizygous pathogenic variant in NDP, c.293 C>T, p.(Pro98Leu), in two brothers with isolated bilateral microphthalmia and sclerocornea were also identified. Pathogenic/likely pathogenic variants were not discovered in the 25 remaining A/M cases. This study underscores the utility of whole-exome sequencing for identification of causative mutations in highly variable ocular phenotypes as well as the extreme genetic heterogeneity of A/M conditions.


Inhibition of endothelial/smooth muscle cell contact loss by the investigational angiopoietin-2 antibody MEDI3617.
A tumor's dependence on angiogenesis for survival and growth has led to the advancement of a variety of blood vessel directed anticancer treatment strategies. Overexpression of angiopoietin-2 (Ang-2) in tumor vasculature and its crucial role in angiogenesis, i.e. the destabilization of endothelial/peri-endothelial cell interactions, now raises the possibility of additional novel anti-angiogenic therapeutics. The present study utilized a co-culture sphere model to (i) demonstrate the destabilizing effect of Ang-2 on endothelial/smooth muscle cell contact and (ii) evaluate the impact of the investigational Ang-2 antibody MEDI3617 on endothelial/smooth muscle cell dissociation. Real time imaging of spheres showed both exogenous Ang-2 and PMA induced endogenous Ang-2 secretion resulted in sphere destabilization (loss of endothelial cells from smooth muscle cell core). The presence of MEDI3617 inhibited this process. To assess the anti-angiogenic potential of MEDI3617 in vivo, nude mice were injected intradermally with human renal cell carcinoma cells (Caki-1, Caki-2) and the number of blood vessels induced over a 3 day period was scored. MEDI3617 (2, 10, 20 mg/kg) significantly reduced the initiation of blood vessels for both tumor models at all doses investigated. These data indicate that MEDI3617 treatment significantly impairs the initiation of angiogenesis by inhibiting the Ang-2 mediated disruption of endothelial/muscle cell interaction associated with blood vessel destabilization and thereby reduces tumor cell induced angiogenesis. The results support the notion that targeting the angiopoietin/Tie2 axis may offer novel anti-angiogenic strategies for cancer treatment.


An integrated System Dynamics model for Closed Loop Supply Chains under disaster effects: The case of COVID-19.
For a Closed Loop Supply Chain (CLSC), disaster is a risk source of unknown-unknowns, which may result in production disruptions with significant consequences on -but not limited to-profitability. For this reason, we provide a System Dynamics (SD)-based analysis for disaster events on the operation of CLSCs in order to study the system response (production/collection/disassembly/remanufacturing/recycling rates, inventories, cost, profit). This response is examined through the dynamics at a manufacturer, parts producer, collector, and disassembly center level, by providing control mechanisms for resilient CLSCs under disaster effects. In this dynamic analysis, COVID-19 is treated as a disaster event. Five different business scenario settings are presented for the manufacturer, which are considered as alternative mitigation policies in responding to product demand. The extensive simulation results provide insights for policy-makers, which depend on the reduction in manufacturer's production, reduction in product demand and duration of recovery period which are considered as causal effects due to the COVID-19 outbreak. For all combinations, holding base stocks during the pre-disaster period is proposed as the best mitigation policy in terms of manufacturer's inventory. In terms of economic impact, holding base stocks or coordination with third party are revealed as the best choice depending on the combination, while remote inventory policy adoption as the worst choice.


Differential effects of stress stimuli on a JNK-inactivating phosphatase.
Stress signals elicit a wide variety of cellular responses, many of which converge on the phosphorylation of JNK and p38 kinases, the activation of which has been well-characterized. How these kinases are switched off by dephosphorylation is not well understood. Here we describe how diverse cellular stresses affect differently the stability and activity of a JNK-inactivating dual-specificity threonine-tyrosine phosphatase M3/6. Both anisomycin and arsenite activate the JNK pathway and, in addition, inactivate the M3/6 phosphatase. However, while anisomycin treatment of cells leads to M3/6 protein degradation, arsenite appears to inactivate M3/6 directly. These results might have implications for the mechanism of tumour promotion by arsenic.


Abdominal aortic aneurysm presenting as paraplegia: case report.
A 65-year-old man with a previously undiagnosed abdominal aortic aneurysm presented with acute paraplegia. Elective resection of the aneurysm was undertaken one week later. Following this, almost complete neurological recovery was regained by 11 months.


Primary care providers' knowledge, beliefs and treatment practices for gout: results of a physician questionnaire.
We sought to examine primary care providers' gout knowledge and reported treatment patterns in comparison with current treatment recommendations. We conducted a national survey of a random sample of US primary care physicians to assess their treatment of acute, intercritical and tophaceous gout using published European and American gout treatment recommendations and guidelines as a gold standard. There were 838 respondents (response rate of 41%), most of whom worked in private practice (63%) with >16 years experience (52%). Inappropriate dosing of medications in the setting of renal disease and lack of prophylaxis when initiating urate-lowering therapy (ULT) accounted for much of the lack of compliance with treatment recommendations. Specifically for acute podagra, 53% reported avoidance of anti-inflammatory drugs in the setting of renal insufficiency, use of colchicine at a dose of ≤2.4 mg/day and no initiation of a ULT during an acute attack. For intercritical gout in the setting of renal disease, 3% would provide care consistent with the recommendations, including initiating a ULT at the appropriate dose with dosing titration to a serum urate level of ≤6 mg/dl and providing prophylaxis. For tophaceous gout, 17% reported care consistent with the recommendations, including ULT use with dosing titration to a serum urate level of ≤6 mg/dl and prophylaxis. Only half of primary care providers reported optimal treatment practices for the management of acute gout and <20% for intercritical or tophaceous gout, suggesting that care deficiencies are common.


Effects of seed size on seedling size in Virola surinamensis; a within and between tree analysis.
We conducted a greenhouse study of the effects of initial seed mass on seedling characteristics in a Panamanian population of Virola surinamensis, a canopy tree in which mean seed mass of different individuals ranges from 1.34 to 4.04g. The system is of particular interest because birds preferentially eat fruits of small-seeded plants, leaving seedlings of large-seeded individuals under conditions of potentially severe sibling competition (Howe and Vande Kerckhove 1980).Effects of differences of mean seed mass between trees are explored using an analysis of variance, while effects of seed-mass variation within crops are demonstrated with a regression analysis. A two-way analysis of variance decisively shows effects of parental source and light condition on seedling height, leaf length, and dry shoot mass (all P<0.0001). A posteriori tests show that differences in seedling characteristics reflect differences in initial seed mass, with especially strong differences apparent in shoot mass. Regression of seedling characteristics on initial seed mass shows that variation of seed size within a crop is sufficient to influence shoot mass at 15 weeks (P<0.0001).Effects of size differences of seeds that land adjacent to each other, either under the parent or in monkey droppings, are documented with growth of pairs of seedlings in pots. Differences in shoot height and mass at 15 weeks are evident when seeds of average size differ by only 0.2 g, and dramatic differences are evident when paired seeds differ by an average of 1.5 g. Seedlings grow more when isolated than when planted with conspecifics.These experimental results offer indirect support for the hypothesis that small-seeded Virola parents secure an advantage in reproduction through differential dispersal, while large-seeded plants produce more competitive seedlings under their own crowns - an advantage most likely to be of importance when frugivores are scarce.


Distinctive features of plant protein kinase CK2.
In plants, protein kinase CK2 is involved in different processes that control many aspects of metabolism and development. In mammals and yeast the enzyme is a heterotetramer composed of two types of subunits. During years the subunit composition of the maize protein kinase CK2 enzyme has been a source of controversy. We have recently characterized the maize holoenzyme subunits. Our results show that multiple catalytic and regulatory subunits are expressed in maize and are able to specifically interact with other alpha and beta subunits suggesting a high level of heterogeneity in the typical heterotetrameric structure. Here, we summarize data available on plant CK2 enzymes, in order to clarify the distinctive features and functions of plant protein kinase CK2.


Clinical and ultrasonographic findings of ovarian tumours in bitches: A retrospective study.
A retrospective study was carried out to investigate incidence, clinical signs and ultrasonographic findings of ovarian tumours in a population of dogs referred to the Veterinary Teaching Hospital of the University of Perugia (Italy) and Anicura Tyrus Veterinary Clinic (Terni, Italy). The period of study ranged from January 2005 to December 2021. A total of 1910 dogs were affected by neoplasia but only 35 of them (1.8%), of different breeds and ages, were found to have ovarian tumours. Ultrasound of the ovaries was performed based on clinical signs; the diagnosis was achieved after ultrasound findings prompted ovariohysterectomy and ovarian pathologic evaluation In our study, the age of bitches affected by ovarian neoplasia ranged from 3 to 20 years (mean 9.6 ± 3.8). The histopathological findings of ovarian masses identified 16 granulosa cell tumours (GCT) (46%), 7 adenomas (20%), 5 adenocarcinomas (14%), 2 teratomas (6%), 1 leiomyoma (3%), 1 luteoma (3%), 1 tecoma (3%), 1 dysgerminoma (3%), and 1 haemangiosarcoma (3%). In particular, with respect to clinical signs, 69% of bitches showed abnormalities of estrus cycle (short interestral interval, persistent estrus, prolonged interestral interval). The other main clinical signs included abdominal distention, palpable abdominal mass, vulvovaginal discharge, polyuria/polydipsia, mammary masses. When present, the laboratory abnormalities were slight anemia and leucocytosis with neutrophilia. The tumours were ultrasonographically classified as mainly solid: 12/35 (34%) (1 adenoma, 4 adenocarcinomas, 1 dysgerminoma, 1 haemangiosarcoma, 1 leyomioma, 1 luteoma, 1 GCT, 1 tecoma, 1 teratoma); solid with cystic component 13/35 (37%) (9 GCT, 2 Adenomas, 1 adenocarcinoma, 1 teratoma); and mainly cystic 10/35 (29%) (6 GCTs, 4 adenomas). In our study, the ultrasound examination allowed us to suspect ovarian neoplasia in asymptomatic subjects referred for breeding management or for preventive health check. On the basis of our data, we proposed to perform a complete periodic examination of the reproductive system once a year from 6 years. Nevertheless, the presence of ovarian neoplasms found in young subjects, during breeding management, suggest including routine ultrasound examination of the reproductive tract.


FABP5 controls macrophage alternative activation and allergic asthma by selectively programming long-chain unsaturated fatty acid metabolism.
Fatty acids (FAs) are widely involved in diverse biological functions. In mice with myeloid-specific deletion of fatty acid-binding protein 5 (FABP5), OVA-induced allergic airway inflammation (AAI) is significantly exacerbated by increasing alternatively activated macrophages (M2). Fabp5 deficiency increases IL-4-induced M2 in vitro. In macrophages, Fabp5 deletion causes significant accumulation of free long-chain unsaturated FAs, such as oleic acid, but does not cause detectable changes to other groups of FAs. Interestingly, excessive uptake of oleic acid aggravates AAI pathogenesis, with increased M2 polarization in bronchoalveolar lavage fluid. Informatics and mechanistic studies indicate that Fabp5 deficiency may reprogram metabolic pathways by enhancing FA β oxidation, tricarboxylic acid cycle, and oxidative phosphorylation, in addition to producing more ATP through activation of the PPARγ signaling pathway, reshaping macrophages in favor of M2 polarization. These results emphasize the importance of FABP5 and oleic acid in AAI, suggesting preventive and therapeutic strategies for allergic asthma.


[Congenital cataract linked to the Y chromosome].
A possible Y linked form of congenital cataract is reported, but an autosomal dominant mode of inheritance cannot be ruled out.


[Molecular and immunohistochemical diagnostics in melanoma].
To provide appropriate therapy and follow-up to patients with malignant melanoma, proper diagnostics are of critical importance. Targeted therapy of advanced melanoma is based on the molecular genetic analyses of tumor tissue. In addition, sequencing of genes and other genetic approaches can provide insight into the origin of melanocytic tumors and can aid in distinguishing benign from malignant lesions. In this regard, spizoid neoplasms remain a challenging entity. Aside from genetic analyses of tumor tissue, immunohistochemistry remains an essential tool in melanoma diagnostics and TNM classification. With new immunotherapies being approved for advanced melanoma, immunohistochemistry to determine PD-L1 expression has gained clinical interest. While PD-L1 expression is associated with response to PD-1 blockade, a substantial number of patients without PD-L1 expression can still experience tumor remission upon treatment. In this review, current and future developments in melanoma diagnostics with regard to molecular genetics and immunohistochemistry are summarized. The utilization of such analyses in clinical decision making is also discussed.


Magnetic oscillatory responses to lateralization changes of natural and artificial sounds in humans.
Oscillatory signals in human magnetoencephalogram were investigated as correlates of cortical network activity in response to sound lateralization changes. Previously, we found lateralized presentations of a monosyllabic word to elicit posterior temporo-parietal gamma-band activity, possibly reflecting synchronization of neuronal assemblies in putative auditory dorsal stream areas. In addition, beta activity was decreased over sensorimotor regions, suggesting the activation of motor networks involved in orientating. The present study investigated responses to lateralization changes of both a barking dog sound and a distorted noise to test whether beta desynchronization would depend on the sound's relevance for orientating. Eighteen adults listened passively to 900 samples of each sound in separate location mismatch paradigms with midline standards and both right- and left-lateralized deviants. Lateralized distorted noises were accompanied by enhanced spectral amplitude at 58-73 Hz over right temporo-parietal cortex. Left-lateralized barking dog sounds elicited right and right-lateralized sounds elicited bilateral temporo-parietal spectral amplitude increases at approximately 77 Hz. This replicated the involvement of posterior temporo-parietal areas in auditory spatial processing. Only barking dog sounds, but not distorted noises, gave rise to 30 Hz desynchronization over contralateral sensorimotor areas, parieto-frontal gamma coherence increases and beta coherence reductions between sensorimotor and prefrontal sensors. Apparently passive listening to lateralized natural sounds with a potential biological relevance led to an activation of motor networks involved in the automatic preparation for orientating. Parieto-frontal coherence increases may reflect enhanced coupling of networks involved in the integration of auditory spatial and motor processes.


Regulation of T cell survival through coronin-1-mediated generation of inositol-1,4,5-trisphosphate and calcium mobilization after T cell receptor triggering.
T cell homeostasis is essential for the functioning of the vertebrate immune system, but the intracellular signals required for T cell homeostasis are largely unknown. We here report that the WD-repeat protein family member coronin-1, encoded by the gene Coro1a, is essential in the mouse for T cell survival through its promotion of Ca2+ mobilization from intracellular stores. Upon T cell receptor triggering, coronin-1 was essential for the generation of inositol-1,4,5-trisphosphate from phosphatidylinositol-4,5-bisphosphate. The absence of coronin-1, although it did not affect T cell development, resulted in a profound defect in Ca2+ mobilization, interleukin-2 production, T cell proliferation and T cell survival. We conclude that coronin-1, through activation of Ca2+ release from intracellular stores, is an essential regulator of peripheral lymphocyte survival.


Deep Learning for the Detection, Localization, and Characterization of Focal Liver Lesions on Abdominal US Images.
To train and assess the performance of a deep learning-based network designed to detect, localize, and characterize focal liver lesions (FLLs) in the liver parenchyma on abdominal US images. In this retrospective, multicenter, institutional review board-approved study, two object detectors, Faster region-based convolutional neural network (Faster R-CNN) and Detection Transformer (DETR), were fine-tuned on a dataset of 1026 patients (n = 2551 B-mode abdominal US images obtained between 2014 and 2018). Performance of the networks was analyzed on a test set of 48 additional patients (n = 155 B-mode abdominal US images obtained in 2019) and compared with the performance of three caregivers (one nonexpert and two experts) blinded to the clinical history. The sign test was used to compare accuracy, specificity, sensitivity, and positive predictive value among all raters. DETR achieved a specificity of 90% (95% CI: 75, 100) and a sensitivity of 97% (95% CI: 97, 97) for the detection of FLLs. The performance of DETR met or exceeded that of the three caregivers for this task. DETR correctly localized 80% of the lesions, and it achieved a specificity of 81% (95% CI: 67, 91) and a sensitivity of 82% (95% CI: 62, 100) for FLL characterization (benign vs malignant) among lesions localized by all raters. The performance of DETR met or exceeded that of two experts and Faster R-CNN for these tasks. DETR demonstrated high specificity for detection, localization, and characterization of FLLs on abdominal US images. Supplemental material is available for this article. RSNA, 2022Keywords: Computer-aided Diagnosis (CAD), Ultrasound, Abdomen/GI, Liver, Tissue Characterization, Supervised Learning, Transfer Learning, Convolutional Neural Network (CNN).


Diurnal variation in the serotonin content and turnover in the pineal gland of the Syrian hamster.
Serotonin and 5-hydroxyindoleacetic acid were measured in the pineal gland of Syrian hamsters by high performance liquid chromatography over a period of 24 h. A distinct 24 h rhythm was detected for both indoles. Turnover studies revealed a higher rate of serotonin synthesis during the day than during the night. We therefore suggest that the serotonin content in the pineal gland of the Syrian hamster is regulated by changes in its synthesis rate, rather than by changes of serotonin catabolism, via N-acetyltransferase activity.


Tau protein is essential for stress-induced brain pathology.
Exposure to chronic stress is frequently accompanied by cognitive and affective disorders in association with neurostructural adaptations. Chronic stress was previously shown to trigger Alzheimer's-like neuropathology, which is characterized by Tau hyperphosphorylation and missorting into dendritic spines followed by memory deficits. Here, we demonstrate that stress-driven hippocampal deficits in wild-type mice are accompanied by synaptic missorting of Tau and enhanced Fyn/GluN2B-driven synaptic signaling. In contrast, mice lacking Tau [Tau knockout (Tau-KO) mice] do not exhibit stress-induced pathological behaviors and atrophy of hippocampal dendrites or deficits of hippocampal connectivity. These findings implicate Tau as an essential mediator of the adverse effects of stress on brain structure and function.