Automated segmentation by deep learning of loose connective tissue fibers to define safe dissection planes in robot-assisted gastrectomy.
The prediction of anatomical structures within the surgical field by artificial intelligence (AI) is expected to support surgeons' experience and cognitive skills. We aimed to develop a deep-learning model to automatically segment loose connective tissue fibers (LCTFs) that define a safe dissection plane. The annotation was performed on video frames capturing a robot-assisted gastrectomy performed by trained surgeons. A deep-learning model based on U-net was developed to output segmentation results. Twenty randomly sampled frames were provided to evaluate model performance by comparing Recall and F1/Dice scores with a ground truth and with a two-item questionnaire on sensitivity and misrecognition that was completed by 20 surgeons. The model produced high Recall scores (mean 0.606, maximum 0.861). Mean F1/Dice scores reached 0.549 (range 0.335-0.691), showing acceptable spatial overlap of the objects. Surgeon evaluators gave a mean sensitivity score of 3.52 (with 88.0% assigning the highest score of 4; range 2.45-3.95). The mean misrecognition score was a low 0.14 (range 0-0.7), indicating very few acknowledged over-detection failures. Thus, AI can be trained to predict fine, difficult-to-discern anatomical structures at a level convincing to expert surgeons. This technology may help reduce adverse events by determining safe dissection planes.


Application of solid-phase antibodies to radioimmunoassay. Improved performance of Dynospheres following affinity purification of antisera.
Affinity purification of antibody before covalent binding to pre-activated micro-particles (Dynospheres) was necessary to overcome the reduced coupling capacity evident with low titre antisera, particularly antihapten sera. Optimally prepared Dynospheres anti-thyroxine provided a radioimmunoassay with good performance and economical usage of microparticles. Assay sensitivity was less than 10 nmol/l while precision across the clinically relevant dose range (50-150 nmol/l) was 3% CV using 125 micrograms particles per assay tube.


"Acute myelogenous leukemia like" translocations in CML blast crisis: two new cases of inv(16)/t(16;16) and a review of the literature.
We describe two patients with CML blast crisis with clonal evolution affecting 16q22 (t(16;16)(p13;q22) and inv(16)(p13;q22), abnormalities of core binding factor, usually found in de novo acute myeloid leukemia (AML)). The bone marrow of both cases showed myelomonocytic (M4) differentiation and eosinophilia. Both patients had prominent extramedullary disease and had poor response to treatment. A literature search focused on patients with CML and additional chromosome changes more typical of AML, revealed that the morphology of the blasts correlated with the finding typical of the underlying "AML" cytogenetic abnormality and an overall very poor clinical outcome, even in the groups with "favorable" AML type translocations.


[6]-gingerol dampens hepatic steatosis and inflammation in experimental nonalcoholic steatohepatitis.
The aim of the study was to investigate the effects of [6]-gingerol ((S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone) in experimental models of non-alcoholic steatohepatitis. HepG2 cells were exposed to 500 µmol/l oleic acid (OA) for 24 h and preincubated for an additional 24 h with [6]-gingerol (25, 50 or 100 µmol/l). [6]-Gingerol (100 µmol/l) inhibited OA-induced triglyceride and inflammatory marker accumulation in HepG2 cells. After being fed a high-fat diet (HFD) for 2 weeks, male golden hamsters were dosed orally with [6]-gingerol (25, 50 or 100 mg/kg/day) once daily for 8 weeks while maintained on HFD. [6]-Gingerol (100 mg/kg/day) alleviated liver steatosis, inflammation, and reversed plasma markers of metabolic syndrome in HFD-fed hamsters. The expression of inflammatory cytokine genes and nuclear transcription factor-κB (NF-κB) were increased in the HFD group; these effects were attenuated by [6]-gingerol. The hepatic mRNA expression of lipogenic genes such as liver X receptor-α, sterol regulating element binding protein-1c and its target genes including acetyl-CoA carboxylase, fatty acid synthase, stearoyl-CoA desaturase 1, and acyl-CoA:diacylglycerol acyltransferase 2 in HFD-fed hamsters was also blocked by [6]-gingerol. [6]-Gingerol may attenuate HFD-induced steatohepatitis by downregulating NF-κB-mediated inflammatory responses and reducing hepatic lipogenic gene expression.


Assessment of element-specific homogeneity in reference materials using microanalytical techniques.
The IAEA established in 1994 a co-ordinated research programme (CRP) on "Reference Materials for Microanalytical Nuclear Techniques" as part of its efforts to promote and strengthen the use of nuclear analytical technologies in member states with the specific aim of improving the quality of analysis of nuclear, environmental, and biological materials. The objectives of this initiative were: to identify suitable biological reference materials which could serve the needs for quality control in microanalytical techniques; to evaluate existing CRMs for use in microanalytical investigations; to evaluate appropriate sample pretreatment procedures for materials being used for analysis with microanalytical techniques; to identify analytical techniques which can be used for characterisation of homogeneity determination, and to apply such techniques to the characterization of candidate reference materials for use with microanalytical techniques. The CRP lasted for 4 years and seven laboratories and the Agency's Laboratories in Seibersdorf participated. A number of materials including the candidate reference materials IAEA 338 (lichen) and IAEA 413 (single cell algae, elevated level) were evaluated for the distribution of elements such as Cl, K, Ca, Cr, Mn, Fe, Zn, As, Br, Rb, Cd, Hg, and Pb. The results obtained during this CRP suggest that: each element exhibits its characteristic distribution in a matrix described by the "Ingamels' sampling constant" or the "relative homogeneity factor" of Kurfuerst; both concepts are valid over a large range of sample mass used for analysis (from 0.1 microg to around 100 mg); and materials being characterised quantitatively for element homogeneity could be used for the experimental determination of total uncertainty of other analytical techniques. As far as we are aware this is the first time the concept of quantitative characterisation of homogeneity has been applied to potential reference materials and the first demonstration of the feasibility and usefulness of the concept with particular emphasis on enhancing quality control opportunities for microanalytical techniques.


Femoral head necrosis and osteopenia in stroke-prone spontaneously hypertensive rats (SHRSPs).
Necrosis of the femoral head and osteopenia were examined histopathologically in stroke-prone spontaneously hypertensive rats (SHRSPs) aged 6 to 36 weeks and compared with that of spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs). Avascular necrosis of the femoral head was frequently observed, mainly in the young SHRSPs and SHRs (about 8 to 15 weeks of age). SHRSPs had the highest incidence of femoral head necrosis among the three strains. This necrotic change in the femoral head was considered to be secondary ischemia induced by angiospasm or arteriosclerosis, similar to the disorders observed in the brain, kidney, and heart in SHRSPs. However, the complication occurred in spite of treatment with antihypertensive agents (ACE inhibitor: enalapril, spirapril) even though other ischemic disorders such as brain hemorrhage and renal infarction were prevented, indicating that the femoral head necrosis in SHRSPs was not due to hypertensive complications induced by angiospasm or arteriosclerosis. Bone mineral density (BMD) of the femoral bone was significantly lower in SHRSPs, and the femoral heads in this strain were the most easily deformed by loads applied during compression tests. Histopathologically, the infarctions were encountered on the lateral side of the epiphysis, but no thrombi were observed. The lateral side of the epiphysis is the anatomic site where the weight load is greatest and the site where the nutritive artery enters. Our results strongly suggest that the coexistence of vulnerable bone matrix and physical weight load to the nutritive artery plays a crucial role in the occurrence of femoral head necrosis in SHRSPs, whether based on generalized or localized osteopenia.


Q-T interval in congenital complete heart block.
The rate-corrected Q-T interval (Q-Tc) was measured in 273 children with congenital complete heart block. Fifty-nine had prolonged Q-Tc and 50 of these had symptoms. All 10 with isolated complete heart block, prolonged Q-Tc and bundle branch block had symptoms. The ventricular rate (VR) was significantly lower in patients with prolonged Q-Tc than in their age-matched controls. The outcome is worse for children with low VR and long Q-Tc than for those with low VR and normal Q-Tc. In 11 children a prolonged Q-Tc preceded symptoms by more than 1 month. This suggests that prolonged Q-Tc in children with congenital complete heart block can be of prognostic significance.


Exposure of council and forestry workers to 2,4,5-T.
The exposure of council and forestry workers to 2,4,5-T, a plant poison, has been monitored for a period of two years. It was found that the excessive urine levels of 2,4,5-T fell dramatically once the exposure was minimized. Therefore, the use of protective clothing and adoption of measures to prevent inhalation exposure are essential.


In vitro evidence for genetic predisposition in some human pancreatic adenocarcinoma.
A numerical alteration in chromosome complement in human dermal fibroblast cultures, hyperdiploidy with a normal occurrence of tetraploidy (IVH) has been reported to be associated with some hereditary single tumors, including pancreatic adenocarcinoma (PaCa). The incidence of IVH was compared in cultures derived from 34 PaCa patients and 39 clinically normal subjects without a family tumor history by three assay systems: (a) percentage of numerically altered metaphases in chromosome preparations (MA); (b) percentage of cells from high-density, stationary cultures with a DNA index (DI) greater than 1 (FCMs); (c) percentage of cells with a DI greater than 2 from cultures of cells undergoing division (FCMd). The last two measurements were obtained by flow cytometric measurement of propidium idodide (PI) stained cells. Concordance was observed between the three assays. There was a linear relationship between the percentage of hyperdiploid metaphases assayed in the chromosome preparation and the percentage of cells with a DI greater than 1 by FCMs and a DI greater than 2 by FCMd. IVH was considered to be present (IVH+) by the MA technique if the percentage of numerically altered metaphases was over 4% exclusive of tetraploids, by the FCMs technique if DI greater than 1 was greater than 10%, and by FCMd if DI greater than 2 was greater than 7%. The assayed group could be divided into two IVH groups on the basis of all three assays, individually or collectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Intravitreal bevacizumab for the treatment of retinopathy of prematurity: a case report.
We report the first case in Scotland of a premature infant treated for retinopathy of prematurity with bevacizumab. A case report and a review of the literature are presented. Retinopathy of prematurity is a leading worldwide cause of childhood blindness. Conventional laser treatment results in destruction of the peripheral retina and does not prevent all cases of vision loss, particularly in Zone I disease. We present the case of a baby born at 26(+3) weeks who developed stage 3+ disease located in Zone I of the retina. The patient was treated with bilateral bevacizumab injections and achieved complete resolution of his retinopathy. Bevacizumab therapy for the treatment of retinopathy of prematurity is an effective and inexpensive treatment that can readily and quickly be administered by a competent ophthalmologist without the need for specialist equipment.


The aggresome pathway as a target for therapy in hematologic malignancies.
Misfolded or unfolded proteins are often refolded with the help of chaperones or degraded by the 26S proteasome. An alternative fate of these proteins is the aggresome pathway. The microtubule-organizing center (MTOC) transports unfolded proteins to lysosomes and are degraded through autophagy. Histone deacetylase 6 (HDAC6) deacetylates alpha-tubulin, which is thought to be a component of the MTOC. Recently, two small molecule inhibitors of the aggresome pathway and HDAC6 have been described. One inhibitor, tubacin, prevents deacetylation of alpha-tubulin and produces accumulation of polyubiquitinated proteins and apoptosis. Tubacin acts synergistically with the proteasome inhibitor, bortezomib, to induce cytotoxicity in one type of hematologic malignancy, multiple myeloma. The other, LBH589, is a pan HDAC inhibitor and hydroxamic acid derivative that induces apoptosis of multiple myeloma cells resistant to conventional therapies. In this review, we summarize recent reports on targeting the aggresome pathway and HDAC6 in hematologic malignancies.


Interocular suppression in adults and infants using anaglyphic stimuli: visually evoked potential measures.
Interocular suppression, assessed by monocular VEP amplitude reduction, was investigated in 3 infants, average age of 3 months, and 8 adults. A dichoptic simultaneous masking paradigm was employed, the two eyes being disassociated by red and green filters which transmitted non-overlapping wave lengths of light (anaglyphic method). One eye was continuously presented with either darkness, a diffuse green light, or two green dot patterns, containing either 20' or 80' dots. The other eye was flashed with either red diffuse light, a red 20' dot pattern, or a red 80' dot pattern. In both adults and infants, monocular VEP amplitude was reduced as the size of the continuously presented dots increased (pattern suppression) and a smaller amplitude response occurred when dots of equal size were presented than when data of different size were presented (size-specific suppression). The relative and absolute magnitudes of interocular pattern suppression were similar for adults and infants. However, the relative and absolute magnitudes of size-specific suppression were larger for adults than for infants. Pattern interocular suppression was inferred to be relatively more mature in 3 month olds than size-specific suppression. The relative lack of size-specific suppression suggests a relative immaturity of binocular spatial frequency or size channels.


Synthesis and cytotoxicity of a biotinylated CC-1065 analogue.
BACKGROUND: The use of pretargeting technology for cancer imaging and treatment has made significant progress in the last few years. This approach takes advantage of the fact that biotin binds strongly to proteins avidin and streptavidin. Thus, a non-toxic tumor cell specific antibody is conjugated with avidin/streptavidin, and is administered to patients. After the antibody binds to tumor cells (usually 24--48 h); a clearing agent is given to remove the residual circulating antibodies in blood. Lastly, a toxic biotin-radioisotope conjugate is administered. Due to the small size of the biotin-radioisotope molecule and tight binding between biotin and avidin/streptavidin, the biotin-radioisotope rapidly binds to tumor cells with high specificity. CC-1065 (1) is one of a few classes of extremely potent antitumor agents, and a biotinalyted CBI-bearing CC-1065 analogue is a promising candidate to be used in the pretargeting technology to treat cancer. RESULTS: A biotinalyted CBI-bearing CC-1065 analogue, 6, was synthesized. The IC50 of 6 was 0.7 nM against U937 cells. Compound 6 caused apototsis of U937 cells. CONCLUSIONS: For the first time, a biotinalyted CBI-bearing CC-1065 analogue, 6, was synthesized. The biotinylated 6 can serve as a model compound to explore the usefulness of non-radioactive small molecule anticancer drugs in the pretargeting strategy for cancer imaging and therapy.


Could prevention of infantile spasms have been possible in a historical cohort of 31 tuberous sclerosis patients?
Efforts to prevent epilepsy in infants with tuberous sclerosis complex (TSC) has been the focus of EPISTOP. The present study was carried out to evaluate whether prevention could have been realistic. A retrospective analysis by hospital chart review of 31 patients with TSC and infantile spasms (practically all patients) admitted to two tertiary hospitals, Children's Hospital, University of Helsinki and Kuopio in 1980-2000. Clinical history, early cognitive development, early clinical signs of TSC, clinical signs of suspicious seizures, first seizures and EEG, response to adrenocorticotropic hormone (ACTH) therapy, EEG and brain imaging were evaluated. Early development prior the spasms was apparently normal in 25 (80%). The first EEG ever performed for a child showed hypsarrhythmia in 16 (51%) or modified hypsarrhythmia in 10 (32%). Treatment lag was short (0-4, mean 2 weeks) and the primary response to ACTH favorable in 19 (64%). Etiological diagnostic workup of IS revealed TSC. In one single case (3%) the diagnosis of TSC could be made at birth due to a congenital cardiac rhabdomyoma. Three other rhabomyomas were diagnosed later. In brain imaging, subependymal periventricular calcifications or hypodense areas were seen in every patient at onset of IS. Other organ manifestations of TSC were retinal phakomas (6), polycystic kidneys (2), and renal angiolipomatosis (1). Preventive treatment of epileptic discharges could have been possible in a single case of neonatal rhabdomyoma suggesting that preventive treatment is challenging in everyday practice. The main obstacle is the delay of TSC diagnosis.


Serum-dependent expression of promyelocytic leukemia protein suppresses propagation of influenza virus.
The rate of propagation of influenza virus in human adenocarcinoma Caco-2 cells was found to negatively correlate with the concentration of fetal bovine serum (FBS) in the culture medium. Virus replicated more rapidly at lower FBS concentrations (0 or 2%) than at higher concentrations (10 or 20%) during an early stage of infection. Basal and interferon (IFN)-induced levels of typical IFN-inducible anti-viral proteins, such as 2',5'-oligoadenylate synthetase, dsRNA-activated protein kinase and MxA, were unaffected by variation in FBS concentrations. But promyelocytic leukemia protein (PML) was expressed in a serum-dependent manner. In particular, the 65 to 70 kDa isoform of PML was markedly upregulated following the addition of serum. In contrast, other isoforms were induced by IFN treatment, and weakly induced by FBS concentrations. Immunofluorescence microscopy indicated that PML was mainly formed nuclear bodies in Caco-2 cells at various FBS concentrations, and the levels of the PML-nuclear bodies were upregulated by FBS. Overexpression of PML isoform consisting of 560 or 633 amino acid residues by transfection of expression plasmid results in significantly delayed viral replication rate in Caco-2 cells. On the other hand, downregulation of PML expression by RNAi enhanced viral replication. These results indicate that PML isoforms which are expressed in a serum-dependent manner suppress the propagation of influenza virus at an early stage of infection.


Consequences of the DYT1 mutation on torsinA oligomerization and degradation.
DYT1 is the most common inherited dystonia, a neurological syndrome that causes disabling involuntary muscle contractions. This autosomal dominant disease is caused by a glutamic acid deletion near the carboxy-terminus in the protein torsinA. Cell- and animal-based studies have shown how the DYT1 mutation causes mutant torsinA to redistribute from the endoplasmic reticulum to the nuclear envelope, acting through a dominant negative effect over the wild type protein. As a result, the wild type:mutant torsinA expression ratio would be important for disease pathogenesis, and events that influence it, such as a differential degradation process for each protein, might modulate DYT1 pathobiology. The DYT1 mutation also triggers the formation of abnormal intermolecular disulfide bonds in torsinA, although the significance of this finding is unclear. How the protein quality control machinery handles torsinA, and whether this process is affected by its abnormal oligomerization remain unknown. Here, we first explored how the disease-linked mutation influences the catabolic process of human torsinA, demonstrating that the differences in subcellular localization between both forms of torsinA lead to divergences in their degradation pathways and, whereas torsinA is normally recycled through autophagy, the proteasome is also required for the efficient clearance of the mutated form. Subsequently, we determined that the abnormal disulfide bond-dependent oligomerization of mutant torsinA is not a result of its redistribution to the nuclear envelope, but a direct consequence of the mutation. Finally, we established that the presence of disulfide links in mutant torsinA oligomers interfere with their degradation by the proteasome, thus relying on autophagy as the main pathway for clearance. In conclusion, the abnormal subcellular localization and oligomerization of DYT1-linked torsinA influences its catabolic process, opening the door to the modulation of the wild type:mutant torsinA ratio through pharmacological manipulation of protein degradation pathways.


Differential expression of CD44 in canine melanocytic tumours.
CD44, the main cell surface receptor for hyaluronan (HA), is often overexpressed in tumour cells, and its presence has been related to cell proliferation and migration. Many of the functions of CD44 are mediated through its interaction with hyaluronan. This study investigated the expression of CD44 in CML-1 and CML-10c2 canine melanoma cell lines and melanoma biopsies, and the production of hyaluronan and versican by the canine melanoma cell lines. Versican is an extracellular proteoglycan that binds hyaluronan, forming a tridimensional pericellular coat surrounding the cells. Both canine melanoma cell lines expressed CD44 and produced HA, but only CML-1 produced versican. Cells expressing all three components (CD44, HA and versican) formed abundant extracellular matrices as demonstrated by a particle exclusion assay. CD44 was present within benign and malignant melanomas, but its expression was more intense in malignant melanomas (P < 0.01). In high CD44-expressing tumours, CD44 tended to be present in the periphery of malignant melanomas, whereas its expression was homogeneous in benign melanomas.


Laparoscopic management of congenital seminal vesicle cysts associated with ipsilateral renal agenesis.
Congenital cysts of the seminal vesicles associated with ipsilateral renal abnormalities are rare. When they are symptomatic, open surgical excision has been the treatment of choice. We present our experience with laparoscopic management and provide a detailed literature review of this entity. Since 1985, 3 patients with symptomatic seminal vesicle cysts and ipsilateral renal agenesis have been treated at our center. Open surgical excision was performed in 1 patient and laparoscopic management was performed in the other 2. Mean patient age was 35.7 years (range 30 to 42). Presenting symptoms were perineal pain in all 3 cases, dysuria in 2, irritable voiding in 2 and testicular pain in 1. Mean laparoscopic operative time was 195 minutes and mean estimated blood loss was 325 cc. Transabdominal or transrectal ultrasound was performed in 2 cases and computerized tomography was performed in all 3. Seminal vesicle cysts associated with ipsilateral renal agenesis are rare but they should be considered in men with otherwise inexplicable irritable voiding symptoms, perineal discomfort or other genitourinary complaint of unclear etiology. Evaluation should include digital rectal examination, transrectal and transabdominal ultrasound, computerized tomography and cystoscopy. Laparoscopy provides excellent intraoperative access and visualization with minimal postoperative morbidity. It is likely to become the treatment of choice for this rare developmental anomaly.


The effects of alpha-latrotoxin of black widow spider venom on synaptosome ultrastructure. A morphometric analysis correlating its effects on transmitter release.
The morphological effects of alpha-latrotoxin, the major component of black widow spider venom, were studied quantitatively in a crude synaptosome fraction (prepared from rat brain cortices) which was incubated at 37 degrees C for 10 min in Ringer solutions. Two toxin concentrations were employed, one causing a very large stimulation of transmitter release (approximately 65% and approximately 43% release of [3H]noradrenaline from preloaded synaptosomes, with and without Ca2+ in the incubation buffer), the other 50-60% as active. Incubated synaptosomes, fixed in suspension with aldehydes, were evenly dispersed in agarose before embedding, to assure randomized sampling in the subsequent morphometric analysis. In all the experimental conditions investigated, alpha-latrotoxin treatment caused a significant decrease in the density (number/unit area) of synaptic vesicles in synaptosome profiles. Such an effect was dose-dependent and partially Ca2+-dependent, in good agreement with the data on transmitter release. At high toxin concentration a moderate increase of synaptosome volume and surface area was observed, both with and without Ca2+. Mitochondrial swelling appeared only in synaptosomes treated in Ca2+ containing medium. These effects of alpha-latrotoxin are similar to those described previously at the neuromuscular junction. Thus, the toxin might be a tool of general use for studying vertebrate synapses.


Ovine submaxillary mucin. Primary structure and peptide substrates of UDP-N-acetylgalactosamine:mucin transferase.
Tryptic digests of ovine submaxillary apomucin were fractionated by gel filtration and ion exchange chromatography to give 14 peptide fractions. Three purified tryptic peptides, representing 106 of the 650 residues in apomucin, were submitted to automated sequence analysis. The NH2-terminal 50 of the 74 residues in one peptide and the entire sequence of the other two hexadecapeptides were established. These studies suggest that purified ovine submaxillary, mucin is chemically homogeneous, containing a unique primary structure without substantial repeating sequences in its polypeptide chain. The sequences adjacent to 28 known O-glycosidically substituted seryl and threonyl residues were compared. No homologies were apparent around the glycosylated seryl and threonyl residues which might define the specificity of the UDP-N-acetylgalactosaminyl:mucin polypeptide transferase that incorporates N-acetylgalactosamine into O-glycosidic linkage in glycoproteins. However, there appears to be a minimum size requirement for glycosylation, because the transferase catalyzes glycosylation of tryptic peptides efficiently, while chymotryptic and thermolytic peptides were much poorer substrates for the transferase.


Challenges, limitations, and solutions for orthodontists during the coronavirus pandemic: A review.
Orthodontic patients worldwide missed appointments during the early months of the coronavirus disease 2019 (COVID-19) pandemic. A significant problem with this virus is its high transmission power. Asymptomatic patients can transmit the virus. The aim of this review is to examine orthodontic emergencies and the necessary strategies and measures for emergency and nonemergency treatment during the coronavirus pandemic. The following databases were comprehensively searched: PubMed, MEDLINE, Scopus, and Google Scholar. Up-to-date data released by major health organizations such as the World Health Organization and major orthodontic associations involved in the pandemic were also evaluated. Few studies were conducted on managing orthodontic offices or clinics during the pandemic, and most are not of high quality. Appropriate communication is the most important issue in managing orthodontic patients, particularly virtual counseling. Many orthodontic emergencies can be managed in this way by patients themselves. Most studies recommend using the filtering facepiece 2 masks, equivalent to N95 masks for non-COVID-19 patients undergoing aerosol-generating procedures and all suspected or confirmed COVID-19 patients in orthodontic visits. At this time, there are no definitive clinical protocols supported by robust evidence for orthodontic practice during the COVID-19 pandemic. Orthodontists should not rush to return to routine orthodontic work and should follow state guidelines. Nonemergency orthodontic visits should be suspended during the severe acute respiratory syndrome coronavirus 2 pandemic in high-risk areas. Resuming orthodontic procedures during the pandemic requires paying special attention to screening, performing maximum efforts to reduce aerosol generation, using appropriate personal protective equipment, having proper ventilation, and fully adhering to sterilization and disinfection principles.


Interstitial lung disease in children.
Children's interstitial lung disease (ILD) includes a wide range of rare respiratory disorders associated with high morbidity and mortality. Genetic factors, systemic disease processes, nonspecific inflammatory or fibrotic patterns of repair seen in a number of clinical settings are involved in the ILD pathogenesis. Specific disorders more prevalent in young children include diffuse developmental disorders, alveolar growth abnormalities, genetic surfactant disorders, pulmonary interstitial glycogenosis and neuroendocrine cell hyperplasia of infancy. It may be difficult to recognize these entities and this can lead to delayed treatment. The diagnostic approach is based on a combination of history/physical examinations, imaging studies, pulmonary function testing, genetic testing, bronchoalveolar lavage (BAL) and in most cases an open lung biopsy. Although some disease types overlap with those seen in adults, in this review emphasis is placed on entities unique to the pediatric population focusing on clinical characteristics, histologic definitions, radiologic-pathologic correlation and therapeutic strategies.


Predictors of herbal medicine use among cancer patients.
Moroccan studies have shown a high frequency of use of traditional and complementary medicines (T&CM). No survey has investigated the predictive factors of the use of traditional herbal medicine. This study aims to assess the prevalence, the determinants, and the predictors of this use. At the regional oncology center of Beni Mellal, we conducted a descriptive and analytical cross-sectional study with 530 adult cancer patients chosen by quota sampling. A 54-item questionnaire was used to perform the face-to-face survey. The Complementary and Alternative Medicine (CAM) healthcare model was used to create this instrument. The prevalence of traditional herbal medicine use was 36.6%. Several variables of the conceptual model were associated with the use of herbal medicine (gender, attitude, and belief towards T&CM, financial resources, and clinical characteristics of patients) (p < 0.05). Predictors of traditional herbal medicine use were female gender (OR = 4.687; p < 0.000), social impact of cancer (OR = 2.314; p < 0.05), emotional impact of cancer (OR = 2.314; p < 0. 05), expected benefits of T&CM use (OR = 3.453; p < 0.000), perceived scientific barriers (OR = 0.580; p < 0.000), perceived socioeconomic barriers (OR = 0.657; p < 0.005), and social norms of relatives (OR = 3.238; p < 0.000). The use of herbal medicine is quite frequent. The profile of users is represented by women who experience pain and the psychosocial impact of cancer and who have positive beliefs about TCMs, are influenced by their relatives and who did not perceive the barriers of this use.


Effects of systemic and regional chemotherapy after hepatic resection for colorectal metastases.
Although the survival benefit of hepatic resection for colorectal metastasis has been established, some controversy remains regarding the significance of adjuvant chemotherapy after hepatic resection. One hundred thirty-two consecutive patients who had liver resection for colorectal metastasis at our hospital between 1980 and 1997 were studied. After curative hepatic resection, 37 patients underwent systemic chemotherapy, administered orally or intravenously, and 38 patients underwent regional chemotherapy, given intra-arterially or intraportally. Forty patients had no adjuvant chemotherapy. The chemotherapeutic agents used for oral administration were uracil and Tegafur or Tegafur alone. Mitomycin C (MMC) or 5-FU was used for IV chemotherapy. Combinations of 5-FU/leucovorin or MMC/5-FU (doxorubicin) were used for regional chemotherapy. Univariate and multivariate analyses were applied to test the significance of adjuvant chemotherapy for patient survival or disease-free survival. Overall 5-year survival was 42.2% (95% CL: 31.2%, 53.2%). Among the possible prognostic factors studied, univariate analysis showed a significant difference in survival based on the number of tumors and lymph node metastases in the hepatic hilum. There was a significant difference in disease-free survival based on adjuvant chemotherapy and lymph node metastasis. The multivariate analysis for patient survival selected four prognostic factors (P < .05), including adjuvant chemotherapy, lymph node metastasis, disease-free interval, and tumor size. The multivariate analysis for disease-free survival selected adjuvant chemotherapy, lymph node metastasis, and disease-free interval as significant factors. The most common recurrence site was remnant liver, regardless of adjuvant chemotherapy. Adjuvant chemotherapy significantly improved survival and disease-free survival after hepatic resection for colorectal metastases. It did not decrease recurrence rate in the remnant liver.


Central 5-HT3 receptor-induced hypothermia is associated with reduced metabolic rate and increased heat loss.
Activation of central 5-HT(3) receptors by the selective agonist m-CPBG (1-(3-chlorophenyl)biguanide hydrochloride, 40 nM i.c.v.) produced stronger hypothermic effect in mice than activation of 5-HT(1A) receptors by their agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propilamino)tetralin) injected by the same route at an equimolar dose. The hypothermic effect of m-CPBG was realized by influence on both the heat production and the heat loss: oxygen consumption and CO(2) expiration were decreased; heat dissipation determined by the tail skin temperature was increased. The heat loss effect of 5-HT(3) receptors was significantly shorter than the decrease in metabolism indicating the prevalent role of heat production decrease in 5-HT(3) receptor-induced deep and long-lasing hypothermia. In addition, the decrease in the respiratory exchange ratio (RER) was shown suggesting that the activation of the 5-HT(3) receptors switched metabolism to prevalent use of lipids as the main energetic substrate. 5-HT(1A) receptor agonist 8-OH-DPAT (40 nM i.c.v.) produced less depressing effect on general metabolism: a decrease in oxygen consumption and CO(2) excretion began later and was not so deep as after m-CPBG administration. Heat-loss effect of 5-HT(1A) receptors activation was not observed. In contrast to m-CPBG effect, RER after 5-HT(1A) receptors activation raised immediately after injection and then gradually decreased to the values observed in m-CPBG-treated mice. Obtained results show that activation of central 5-HT(3) receptors are more effective in hypothermia induction due to marked decrease in thermogenesis and increase in heat loss.


Estimation of amino acid contents in maize leaves based on hyperspectral imaging.
Estimation of the amino acid content in maize leaves is helpful for improving maize yield estimation and nitrogen use efficiency. Hyperspectral imaging can be used to obtain the physiological and biochemical parameters of maize leaves with the advantages of being rapid, non-destructive, and high throughput. This study aims to estimate the multiple amino acid contents in maize leaves using hyperspectral imaging data. Two nitrogen (N) fertilizer experiments were carried out to obtain the hyperspectral images of fresh maize leaves. The partial least squares regression (PLSR) method was used to build the estimation models of various amino acid contents by using the reflectance of all bands, sensitive band range, and sensitive bands. The models were then validated with the independent dataset. The results showed that (1) the spectral reflectance of most amino acids was more sensitive in the range of 400-717.08 nm than other bands. The estimation accuracy was better by using the reflectance of the sensitive band range than that of all bands; (2) the sensitive bands of most amino acids were in the ranges of 505.39-605 nm and 651-714 nm; and (3) among the 24 amino acids, the estimation models of the β-aminobutyric acid, ornithine, citrulline, methionine, and histidine achieved higher accuracy than those of other amino acids, with the R 2, relative root mean square error (RE), and relative percent deviation (RPD) of the measured and estimated value of testing samples in the range of 0.84-0.96, 8.79%-19.77%, and 2.58-5.18, respectively. This study can provide a non-destructive and rapid diagnostic method for genetic sensitive analysis and variety improvement of maize.


Review and inventory of 911 Good Samaritan Law Provisions in the United States.
911 Good Samaritan Laws (GSLs) confer limited legal immunity to bystanders in possession of controlled substances who report emergency overdoses. While these laws may decrease opioid overdose mortality, current literature reduces GSLs to a small number of variables, overlooking substantial differences in implementation and statutory context which dramatically alter their applicability. We identified all state GSLs and their legislative history, characterizing features into four categories using a novel framework: breadth of protected activities, burden placed on Good Samaritans, strength of protection, and exemption in coverage. When protections depended on the nature of the controlled substance, heroin served as a common point of comparison. GSLs vary substantially across states and time. Protections depend on the quantity of substances involved and may extend to the person experiencing the overdose or persons reporting their own overdose. Protected offenses range from possession of controlled substances to drug-induced homicide. In some states, Good Samaritans must complete substance use treatment or administer naloxone to retain protections. Immunity ranges from protection from arrest to merely procedural protections at trial, and may even exclude persons in possession of opioids. Exemptions target persons engaging in chronic substance use, such as persons invoking protection multiple times or previously reporting an overdose. States offer Good Samaritans substantially different protections even when the statutes confer nominally comparable immunities. Accommodating this heterogeneity will enhance the validity of future studies into these laws and their efficacy.


Progression of Pachychoroid Neovasculopathy into Aneurysmal Type 1 Choroidal Neovascularization or Polypoidal Choroidal Vasculopathy.
To describe the progression of pachychoroid neovasculopathy (PNV) into pachychoroid aneurysmal type 1 choroidal neovascularization (PAT1)/polypoidal choroidal vasculopathy (PCV). Retrospective longitudinal cohort study. Patients diagnosed with PNV with a follow-up of ≥2 years. Multimodal imaging, including OCT and fluorescein and indocyanine green angiography, was reviewed for the presence of choroidal neovascularization (CNV), aneurysms within/at the margins of the CNV, and subfoveal choroidal thickness (SFCT). Rate of PNV to PAT1/PCV conversion and risk factors thereof. In total, 37 eyes of 32 patients with PNV with a mean follow-up of 3.3 ± 1.1 years (range, 2.0-5.2) were included in the study. At PNV diagnosis, the mean age was 59.7 ± 8.7 years (range, 38.5-78.0 years) and mean SFCT was 357 ± 92 μm (185-589). During the follow-up, 5 (13.5%) eyes developed aneurysms after a mean 3.4 ± 0.8 years (2.3-4.2), defining PAT1/PCV. The risk of PAT1/PCV conversion was 7.4% at year 3, 13.6% at year 4, and 30.7% at year 5. A mean of 5.2 ± 4.0 to 7.9 ± 3.6 intravitreal anti-VEGF injections were given per year, resulting in a significant reduction of SFCT to 317 ± 104 μm (122-589) (P = 0.0007). The age at diagnosis of PNV was significantly lower in eyes that later went on to develop PAT1/PCV (54.0 ± 5.6 [45.9-60.5] vs. 61.2 ± 8.4 [38.5-78.0] years; P = 0.025). At the end of the follow-up, SFCT had on average decreased by -14.0% ± 17.6% (-55.9% to 23.1%) in the PNV group, whereas it had increased by mean 6.9% ± 4.4% (0.00%-10.8%) in the PAT1/PCV conversion group (P = 0.0025). PNV can develop aneurysms within its type 1 CNV, defining the conversion to PAT1/PCV. In this study, the conversion to PAT1/PCV was seen in 13.5% of eyes, resulting in Kaplan-Meier estimates of risk for conversion of 7.4% at year 3, 13.6% at year 4, and 30.7% at year 5. Younger age at diagnosis of PNV and sustained choroidal thickening despite anti-VEGF therapy might be risk factors for PNV to progress into PAT1/PCV.


Is Dietary Nonadherence Unique to Obesity and Weight Loss? Results From a Randomized Clinical Trial.
Weight stigma is associated with poor dietary adherence, yet adherence is essential for weight loss and maintenance. This study aimed to determine differences in dietary adherence and perceived hunger between lean individuals and two groups of individuals with obesity. In a 6-week outpatient dietary intervention (23 males; aged 48 [SD 14] years), lean participants (n = 23; BMI 23 [SD 2] kg/m2 ) received a weight-maintaining energy needs (WMEN) diet, and participants with obesity (BMI 36 [SD 7]) were randomized to either WMEN (n = 18) or a 35% calorie-reduced (CR) diet (n = 19). All food was provided, and multiple adherence and hunger ratings were assessed daily and weekly on an outpatient basis and in person at twice-weekly visits (e.g., 24-hour recall, diaries). Weight decreased more in the group of CR individuals with obesity (β = -0.301 kg/wk, P = 0.02) compared with the group of lean individuals and the group of WMEN individuals with obesity. However, total percent adherence did not differ between groups (P = 0.60), and hunger scores did not change across groups over time (P = 0.08). Results indicate that there are no differences in dietary adherence between lean individuals and individuals with obesity and adherence is not associated with adiposity or hunger. Thus, the belief that nonadherence (e.g., lack of willpower) is unique to obesity is untrue and may perpetuate weight bias and stigma.


Intracoronary Administration of Thrombolysis for Severe Coronary Artery Ectasia Presenting as an Acute Inferior ST-Segment Elevation Myocardial Infarction.
We present a 75-year-old male with acute inferior ST-elevation myocardial infarction, severe coronary artery ectasia, and large thrombus burden in the right coronary artery to support the use of intracoronary thrombolysis as a second-line therapy for a large thrombus burden in primary percutaneous coronary intervention.


[Neo-natal chylothorax: antenatal echographic diagnosis and favourable outcome].
A case of right chylothorax in a male neonate is reported. A sonographic diagnosis was made during the 35th week of pregnancy. A complete recovery was obtained with appropriate dietetic therapy.


Montreal Cognitive Assessment Performance in HIV/AIDS: Impact of Systemic Factors.
A large proportion of people living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) suffer from neurocognitive impairment (NCI). The causes of the NCI are multifold in HIV infection although a subset of HIV/AIDS patients are affected by the spectrum syndrome, HIV-associated neurocognitive disorder (HAND). We investigated the Montreal Cognitive Assessment (MoCA) in relation to clinical, demographic and laboratory findings as well as its ability to predict symptomatic HAND (sHAND) among patients with HIV/AIDS. All subjects were receiving regular HIV care including CD4+ T cell counts, plasma viral load measurements, clinical evaluations and antiretroviral therapy. The diagnosis of sHAND was based upon clinical, neuroimaging, and neuropsychological assessments. Among HIV-1 seropositive subjects (n=125), ethnicity, education and employment were positively correlated with their MoCA scores (p<0.05). In contrast, polypharmacy, central nervous system penetration-effectiveness (CPE) score, antiretroviral drug exposure, substance use and nucleoside/nucleotide reverse transcriptase inhibitor side effects were negatively correlated with MoCA scores (p<0.05). Of note, MoCA scores were not associated with CD4 T cell nadir levels, age, peak viral load, or veterans aging cohort study index. In subjects with or without sHAND, mean MoCA scores differed (sHAND, 22.8±3.51; non-HAND 25.2±2.64) (p<0.05) with a receiver operating characteristic curve showing an area under curve of 0.71 and an optimal MoCA cut-off value of 23.5 when compared to the established diagnostic paradigm. MoCA scores were generally lower in this HIV/AIDS population compared to reported scores in the general population. MoCA performance was associated with multiple clinical variables but displayed limited predictive utility in detecting sHAND.


Psychometric Properties of The Five-Item Victimization of Exploitation (FIVE) Scale: A Measure of Financial Abuse of Older Adults.
Elder mistreatment affects at least 1 in 10 older adults. Financial abuse, or exploitation, of older adults is among the most commonly reported forms of abuse. Few validated measures exist to measure this construct. We aim to present a new psychometrically validated measure of financial abuse of older adults. Classical test theory and item response theory (IRT) methodologies were used to examine a five-item measure of financial abuse of older adults, administered as part of the New York State Elder Mistreatment Survey. Factor analysis revealed a single factor best fits the data, which we labeled as financial abuse. Moreover, IRT analyses revealed that these items discriminated well between abused and nonabused persons and provided information at high levels of the latent trait θ, as is expected in cases of abuse. The Five-Item Victimization of Exploitation Scale has acceptable psychometric properties and has been used successfully in large-scale survey research. We recommend this measure as an indicator of financial abuse in elder abuse, or mistreatment prevalence research studies.


Acute handling stress downregulates benzodiazepine receptors: reversal by diazepam.
In rats naive to handling, the effects of an acute handling stress led to lower [3H]flunitrazepam binding in the frontal cortex, compared with animals previously habituated to handling for 2 or 21 days. This decreased binding was due to reductions in the number of receptors, not to change in affinity. Pre-incubation with diazepam (0.3, 3.0 or 30 microM) of frontal cortex homogenates taken from naive rats exposed to acute handling stress (followed by extensive washing to remove residual diazepam and endogenous modulators) led to a concentration-dependent increase in the number benzodiazepine receptors, without any change in KD. Acute in vivo administration of diazepam (4 mg/kg) prior to the handling stress was without significant effect in handling-habituated animals, but increased [3H]flunitrazepam binding in handling naive rats. Thus, handling habituation and diazepam treatment have similar actions on benzodiazepine binding and represent two ways of adapting to the stress of handling by increasing the number of benzodiazepine receptors.


Imipramine for the treatment of fibrositis: a therapeutic trial.
Twenty fibrositic patients were treated with imipramine 50-75 mg/day. Only two patients responded favourably. Nineteen patients stopped therapy during the initial three-month period: 14 of them due to lack of response, while two of these concomitantly disclosed side effects. The additional five patients stopped therapy mainly due to side effects, while only one of them improved with therapy. One patient, only, improved and adhered to therapy for more than three months.


[Clinical assessment of chronic prostatitis based on infrared imaging technology].
To investigate the characteristic changes in the infrared thermogram of chronic prostatitis (CP) patients and find some evidence for the auxiliary diagnosis and therapeutic evaluation of the disease. Fifty CP patients and 20 healthy male volunteers were included in this clinical trial. The infrared thermograms of the subjects were compared between the two groups for characteristic changes. The values obtained were used for the auxiliary diagnosis and therapeutic evaluation of the disease. Compared with the healthy males in the same age group, the CP patients showed extremely significant abnormal changes in the average temperature value in the hypogastrium (H), pubis (P), scrotum (S), and groin (G) (P < 0.01). The average H temperature value of the CP patients was correlated negatively with the CP symptom index (CPSI) (P < 0.01, Pearsons correlation coefficient = -0.519), while the S temperature positively with CPSI (P < 0.01, Pearsons correlation coefficient = 0.446). In addition to the H value, the P, S, and G values were all correlated in different degrees with CPSI (P < 0.01), which the S value exhibited the most significantly negative correlation (Pearson's correlation coefficient = -0.898). There are some characteristic changes in the hypogastrium temperature of CP patients in the infrared thermogram, which has a potential application value for the auxiliary diagnosis, symptom assessment, and therapeutic evaluation of CP.


Intakes and sources of total and added sugars among 4 to 13-year-old children in China, Mexico and the United States.
Intakes of dietary sugars is a global concern, and many national and international organizations have set targets to limit consumption. However, it is unclear to what extent intakes of total and added sugars vary between geographies. The aim of this study was to assess the differences in intakes of total and added sugars in 4 to 13-year-old children in China, Mexico and the United States. The secondary aim was to identify main sources of total and added sugars in the diets of these children. Secondary data analysis was conducted using the 2011 China Health and Nutrition Survey, 2012 Mexican National Health and Nutrition Survey, and 2009-2012 US National Health and Nutrition Examination Surveys. Total and added sugar intakes were calculated using the US Food Patterns Equivalents Database. Mean intakes of total and added sugars were 26 and 9 g d-1 among Chinese children, 92 and 55 g d-1 among Mexican children, and 124 and 76 g d-1 among US children, respectively. The top food sources of total sugars were fruits among Chinese children, and sugar-sweetened beverages and milk-based beverages among Mexican and US children. These data highlight the heterogeneity of food patterns worldwide and the need for adapted country-specific public health recommendations on sugars.


Primary anetoderma: a cutaneous sign of antiphospholipid antibodies.
Although a few reports in recent years have suggested that patients with antiphospholipid antibodies (aPL) are prone to developing primary anetoderma (PA), it is still unclear how often aPL are detected in unselected PA patients. We studied nine consecutive PA patients for the presence of autoimmune antibodies and disorders in general and the presence of aPL in particular. Six of the nine patients had clinical evidence of associated autoimmune disorders (Graves'disease and autoimmune haemolysis in one, systemic scleroderma in one, Hashimoto's thyroiditis in one, alopecia areata in one) and/or signs of hypercoagulability (recurrent fetal loss in two, recurrent stokes in one, recurrent deep vein thrombosis in one). In four ofthese six patients the onset of PA preceded these signs. Positive aPL was found in all: anticardiolipin (aCL) in six, anti-beta2-glycoprotein-I (a(beta)2GPI) in six and lupus anticoagulant (LAC) in four. The most frequent isotype was IgA. Among other autoantibodies found the most frequently was antinuclear antibodies. Four ofthe nine patients fulfilled the criteria for antiphospholipid syndrome (APS). It is concluded that PA is an important cutaneous sign for autoimmune disorders in general and the presence of aPL in particular. Hence, the work-up of these patients should include testing for LAC as well as for all different isotypes ofaCL and a(beta)2GPI. We recommend that PA be added to the list of the cutaneous manifestations of APS.


Annotation of AMP-activated protein kinase genes and its comparative transcriptional analysis between high and low lipid producing strains of Mucor circinelloides.
AMP-activated protein kinase (AMPK) is an important regulator for lipid accumulation, potentially known to have an inhibitory role in lipid synthesis. It inactivates acetyl-CoA carboxylase (ACC), an important regulatory enzyme required for lipid synthesis. However, in Mucor circinelloides, AMPK and its association with lipid accumulation has not been studied yet. To identify AMPK genes in M. circinelloides and to compare their expression levels in high and low lipid-producing strains of M. circinelloides to predict the possible roles of AMPK in lipid metabolism and to select candidate genes for further studies to enhance lipid accumulation. Two genes for α-subunit, one for β-subunit and six for γ-subunit were identified and annotated. Bioinformatic analysis confirmed the presence of typical conserved domains in these genes. Furthermore, transcriptional profiling displayed marked differences in expression kinetics of subunits among the selected strains. The expression of AMPK genes decreased rapidly in WJ11, high lipid producer strain during the lipid accumulation phase while contrasting profile of expression was observed in CBS 277.49, low lipid producer strain. The present study has shown the association of AMPK genes with lipid metabolism at the transcriptional level. The involvement of Snf-α1, Snf-α2, Snf-β, Snf-γ1, Snf-γ4, Snf-γ5 subunits were shown to be more pronounced and could potentially be further explored in future studies.


Characterization of pure high-grade DCIS on magnetic resonance imaging using the evolving breast MR lexicon terminology: can it be differentiated from pure invasive disease?
Magnetic resonance imaging (MRI) is now a recognized method of imaging the breast. Unfortunately, there is lack of standardization in the MRI terminology used to characterize the appearance of breast lesions. Moreover, cases of mixed histologies are often imaged. We retrospectively identified cases of pure high-grade ductal carcinoma in situ (DCIS) using the recently introduced breast MRI lexicon and characterized the lesions in order to try and identify features that might distinguish high-grade DCIS from invasive disease. Five-year review of our institution's database revealed 637 patients underwent gadolinium-enhanced breast MRI examination. Twenty patients had histologically proven pure high-grade DCIS. After excluding patients with previous chemotherapy or inadequate MRI examination, 13 patients were analyzed and compared to the 13 most recent cases of pure invasive breast carcinoma. The morphological and dynamic features were then compared. High-grade DCIS cases were significantly more likely to show focal branching pattern (P=.03) and to have an irregular contour (P=.03), compared with invasive disease. Although of marginal statistical significance, DCIS lesions are more likely to have a lower morphological score than invasive carcinoma (P=.06), whilst the latter is more likely to show ring enhancement (P=.07). Use of breast MRI for staging at our institution shows that pure DCIS and pure invasive cancers are both rare entities. Despite the relatively limited numbers, we identified features that would help to differentiate high-grade DCIS from invasive carcinoma on MRI.


Evolutionary coexistence in a metacommunity: Competition-colonization trade-off, ownership effects, environmental fluctuations.
We study the adaptive dynamics of the colonization rate of species living in a patchy habitat when there is a trade-off with the competitive strength for individual patches. To that end, we formulate a continuous-time competition-colonization model that also includes ownership effects as well as random disturbance affecting the mortality rate. We find that intermediate disturbance (as measured by the fluctuation intensity of the mortality rate), a strong competition-colonization trade-off, and a weak ownership effect are necessary conditions for evolutionary branching and hence for the emergence of polymorphisms (i.e., coexistence) by small evolutionary steps. Specifically, concerning ownership we find that with low-intermediate disturbance, a weak ownership advantage favours evolutionary branching while ownership disadvantage does not. This asymmetry disappears at the higher-intermediate disturbance. Moreover, at a low-intermediate disturbance, the effect of the strength of the competition-colonization trade-off on evolutionary branching is non-monotonic disappears because the possibility of branching disappears again when the trade-off is too strong. We also find that there can be multiple evolutionary attractors for polymorphic populations, each with its own basin of attraction. With small but non-zero random evolutionary steps and depending on the initial polymorphic condition just after branching, a coevolutionary trajectory may come arbitrarily close to the shared boundary of two such basins and may even jump from one side to the other, which can lead to various kinds of long-term evolutionary dynamics, including evolutionary branching-extinction cycles.


Contributions of theoretical modeling to the understanding of neural map development.
Theoretical/computational models have played an important role in developing our understanding of the fundamental mechanisms involved in neural map formation. I review models based on both chemospecific and activity-dependent matching of inputs to targets, with a particular focus on map development in the optic tectum and primary visual cortex.


Overexpression of transglutaminase 4 and prostate cancer progression: a potential predictor of less favourable outcomes.
Transglutaminase 4 has been shown to enhance various biological properties of prostate cancer cells, e.g., cell-matrix adhesion, invasiveness and the epithelial-mesenchymal transition. The objectives of this study were to investigate the associations between transglutaminase 4 expression and the established features and biochemical recurrence of prostate cancer. Transglutaminase 4 immunostaining was performed on a tissue microarray. The expression of transglutaminase 4 was evaluated by a scoring method based on the intensity and extent of staining. The clinical and pathological information was obtained through a review of medical records. Follow-up data were obtained by consulting the hospital medical records and the prostate cancer database of our department and by contacting patients or family members. We then compared the transglutaminase 4 expression levels between the prostate cancer tissues and the paracarcinoma tissues and evaluated the correlation of transglutaminase 4 expression with the clinical parameters and biochemical recurrence of prostate cancer. Our results indicated that the transglutaminase 4 staining was significantly higher in tumour tissue than in paracarcinoma tissue (P<0.001) and was positively associated with higher Gleason score (P<0.001) and higher prostate-specific antigen level (P=0.005). Patients with transglutaminase 4 overexpression experienced shorter biochemical recurrence-free survival after surgery (P=0.042) in the univariate analysis but not in the multivariate analysis (P=0.139), which indicated that transglutaminase 4 may serve as a potential predictor of biochemical recurrence of prostate cancer.


The novel HLA-C*03:605 allele, identified using next-generation sequencing in a Chinese individual.
The HLA-C*03:605 allele differs from HLA-C*03:04:01:01 by a single nucleotide in exon 4, position 680.


Identification and quantification of multi-class veterinary drugs and their metabolites in beef using LC-MS/MS.
The practice of abusing antibiotics to improve livestock growth poses a threat to food safety. To prevent and regulate this, accurate monitoring of residual veterinary drugs (VDs) is required. A method based on QuEChERS with dispersive solid-phase extraction for the determination of multi-class VDs was investigated using selected product ions under optimized multiple reaction monitoring conditions. During the clean-up procedure, chitosan, octadecyl silica, primary-secondary amine, and enhanced matrix removal (EMR)-lipid were evaluated for simultaneous analysis of multi-class VDs in beef matrix. The EMR sorbent was most advantageous (113/115) compared to others, and showed a satisfactory recovery range (70.7-117.9%) except cefquinome (67.3%) and cefalonium (69.8%). This methodology can be used to detect oxolinic acid and ractopamine (27.4% and 88.0% of maximum residue limit, respectively) in real beef samples. We thus study propose a simple and fast analytical method for multi-class VDs for the future health of humans and animals.


Clinical epidemiology of pulmonary aspergillosis in hospitalized patients and contribution of Cyp51A, Yap1, and Cdr1B mutations to voriconazole resistance in etiologic Aspergillus species.
Pulmonary aspergillosis is a life-threatening fungal infection with worldwide distribution. In the present study, clinical epidemiology of pulmonary aspergillosis and antifungal susceptibility of etiologic Aspergillus species were evaluated in one-hundred fifty patients with special focus on the frequency of voriconazole resistance. All the cases were confirmed by the clinical pictures, laboratory findings, and isolation of etiologic Aspergillus species which belonged to two major species, i.e., A. flavus and A. fumigatus. Seventeen isolates displayed voriconazole MIC greater than or equal to the epidemiological cutoff value. Expression of cyp51A, Cdr1B, and Yap1 genes was analyzed in voriconazole-intermediate/resistant isolates. In A. flavus, Cyp51A protein sequencing showed the substitutions T335A and D282E. In the Yap1 gene, A78C replacement led to Q26H amino acid substitution that was not reported previously in A. flavus resistant to voriconazole. No mutations associated with voriconazole resistance were found in the three genes of A. fumigatus. The expression of Yap1 was higher than that of two other genes in both A. flavus and A. fumigatus. Overall, voriconazole-resistant strains of both A. fumigatus and A. flavus demonstrated overexpression of Cdr1B, Cyp51A, and Yap1 genes compared to voriconazole-susceptible strains. Although there are still ambiguous points about the mechanisms of azole resistance, our results showed that mutations were not present in majority of resistant and intermediate isolates, while all of these isolates showed overexpression in all three genes studied. As a conclusion, it seems that the main reason of the emergence of mutation in voriconazole-resistant isolates of A. flavus and A. fumigatus is previous or prolonged exposure to azoles.


The cell cycle dependence of c-sis gene expression: artifactual conclusions in cells prepared by chemical but not physical techniques.
The c-sis oncogene encoding the B-chain of platelet-derived growth factor (PDGF) may be involved in an autocrine growth stimulation of tumours expressing the PDGF receptor, such as glioblastomas and sarcomas. To investigate whether expression of c-sis RNA is regulated in a cell cycle dependent manner, human A172 glioblastoma cells were synchronized by either centrifugal elutriation or chemical blockage with the DNA synthesis inhibitors hydroxyurea or aphidicolin. In non-perturbed elutriated cells, c-sis RNA levels were lower in the S phase of the cell cycle than in the G1 phase. In contrast, the chemically synchronized cells revealed a transient rise in c-sis RNA shortly after drug release, in early S phase. The RNA changes occurring after release from drug inhibition represent cell recovery from drug induced metabolic disturbances rather than true cell cycle dependent effects.


Mortality in cancer patients with SARS-CoV-2 or seasonal influenza: an observational cohort study from a German-wide hospital network.
At the beginning of the COVID-19 pandemic, SARS-CoV-2 was often compared to seasonal influenza. We aimed to compare the outcome of hospitalized patients with cancer infected by SARS-CoV-2 or seasonal influenza including intensive care unit admission, mechanical ventilation and in-hospital mortality. We analyzed claims data of patients with a lab-confirmed SARS-CoV-2 or seasonal influenza infection admitted to one of 85 hospitals of a German-wide hospital network between January 2016 and August 2021. 29,284 patients with COVID-19 and 7442 patients with seasonal influenza were included. Of these, 360 patients with seasonal influenza and 1625 patients with COVID-19 had any kind of cancer. Cancer patients with COVID-19 were more likely to be admitted to the intensive care unit than cancer patients with seasonal influenza (29.4% vs 24.7%; OR 1.31, 95% CI 1.00-1.73 p < .05). No statistical significance was observed in the mechanical ventilation rate for cancer patients with COVID-19 compared to those with seasonal influenza (17.2% vs 13.6% OR 1.34, 95% CI 0.96-1.86 p = .09). 34.9% of cancer patients with COVID-19 and 17.9% with seasonal influenza died (OR 2.45, 95% CI 1.81-3.32 p < .01). Risk factors among cancer patients with COVID-19 or seasonal influenza for in-hospital mortality included the male gender, age, a higher Elixhauser comorbidity index and metastatic cancer. Among cancer patients, SARS-CoV-2 was associated with a higher risk for in-hospital mortality than seasonal influenza. These findings underline the need of protective measurements to prevent an infection with either COVID-19 or seasonal influenza, especially in this high-risk population.


Circ_0000442 functions as a tumor repressor in breast cancer by impacting miR-1229-3p and upregulating ZBTB1.
A variety of circular RNAs (circRNAs) have tumor-regulatory roles in breast cancer (BC). Circ_0000442 was reported to inhibit the progression of BC, and this study was designed to explore the novel functional mechanism of circ_0000442 in BC. The expression analysis for circ_0000442, microRNA-1229-3p (miR-1229-3p) and zinc finger and BTB domain containing 1 (ZBTB1) was performed using the quantitative real-time polymerase chain reaction (qRT-PCR). Dual-luciferase reporter assay was used to affirm the target interaction. Cell proliferation was examined using Edu assay and colony formation assay. Cell migration and invasion were assessed by transwell assay. Flow cytometry was applied for the detection of cell apoptosis. Glycolysis was analyzed using the detection kits to measure the glucose consumption and lactate production. The protein expression levels were determined by western blot. The role of circ_0000442 in BC in vivo was explored using tumor xenograft assay. Circ_0000442 expression was downregulated and miR-1229-3p expression was upregulated in BC tissues and cells. Circ_0000442 directly interacted with miR-1229-3p. Circ_0000442 repressed proliferation, migration, invasion and glycolysis but promoted apoptosis in BC cells. The anti-tumor role of circ_0000442 was attributed to the sponge effect on miR-1229-3p. ZBTB1 was a downstream target for miR-1229-3p. Downregulation of miR-1229-3p blocked the malignant behaviors in BC cells by elevating the expression of ZBTB1. Circ_0000442 regulated the ZBTB1 level by targeting miR-1229-3p, and it inhibited tumor growth of BC in vivo by mediating the miR-1229-3p/ZBTB1 axis. All evidence unraveled that circ_0000442 impeded the progression of BC by sponging miR-1229-3p to evoke the ZBTB1 expression upregulation.


Skin microcirculation and regional peripheral resistance in patients with chronic renal anaemia treated with recombinant human erythropoietin.
Skin microcirculation and regional peripheral resistance were studied in 14 patients with renal anaemia during therapy with recombinant human erythropoietin. Haematocrit was raised from 20.0 to 31.3% after 10-12 weeks of treatment and remained stable over another period of 12 weeks. Antihypertensive treatment had to be intensified in five patients. Regional calf blood flow decreased significantly; accordingly, calculated peripheral vascular resistance was increased by more than 100%. However, transcutaneous oxygen pressure (37 degrees C and 44 degrees C) increased significantly. The pathological vasoconstrictor response of skin capillaries was not influenced. There were no significant differences of any parameter between the patients requiring reinforced antihypertensive therapy and those with stable blood pressure. In conclusion skin oxygenation may be improved by erythropoietin treatment to a large extent despite an increase in calculated total limb vascular resistance.


Selective argon laser suturelysis versus needle suturelysis to treat induced corneal astigmatism after cataract surgery.
To compare the complications and subjective experience of patients having argon laser suturelysis (LS) with those of patients having needle suturelysis (NS) for corneal astigmatism after extracapsular cataract extraction (ECCE). Department of Ophthalmology, Tan Tock Seng Hospital, Singapore. This prospective study comprised 30 patients (30 eyes) with more than 3.00 diopters of with-the-rule astigmatism after ECCE. A minimum of 5 weeks after surgery, 2 sutures along the steepest meridian were lysed by the same surgeon, 1 by a needle and the other by laser using a Hoskins lens. Patients were randomized to receive NS first followed by LS or LS followed by NS. The complications were recorded. The patients subjectively graded their fear and discomfort/pain during suturelysis using a scale from 0 to 10. Patient preference for either procedure was also recorded. The complications of NS were conjunctival epithelial defect (17/30), subconjunctival hemorrhage (13/30), and corneal abrasion (4/30) and of LS, minor conjunctival burn (1/30) and conjunctival epithelial defect (1/30). The mean subjective fear and discomfort/pain scores in the NS group were significantly higher than in the LS group (P =.0010 and P =.0014, respectively). Nineteen patients preferred LS, 3 preferred NS, and 8 had no preference for either procedure. Argon laser suturelysis was associated with fewer complications than NS and was preferred by patients.


In-silico assessment of high-risk non-synonymous SNPs in ADAMTS3 gene associated with Hennekam syndrome and their impact on protein stability and function.
Hennekam Lymphangiectasia-Lymphedema Syndrome 3 (HKLLS3) is a rare genetical disorder caused by mutations in a few genes including ADAMTS3. It is characterized by lymphatic dysplasia, intestinal lymphangiectasia, severe lymphedema and distinctive facial appearance. Up till now, no extensive studies have been conducted to elucidate the mechanism of the disease caused by various mutations. As a preliminary investigation of HKLLS3, we sorted out the most deleterious nonsynonymous single nucleotide polymorphisms (nsSNPs) that might affect the structure and function of ADAMTS3 protein by using a variety of in silico tools. A total of 919 nsSNPs in the ADAMTS3 gene were identified. 50 nsSNPs were predicted to be deleterious by multiple computational tools. 5 nsSNPs (G298R, C567Y, A370T, C567R and G374S) were found to be the most dangerous and can be associated with the disease as predicted by different bioinformatics tools. Modelling of the protein shows it can be divided into segments 1, 2 and 3, which are connected by short loops. Segment 3 mainly consists of loops without substantial secondary structures. With prediction tools and molecular dynamics simulation, some SNPs were found to significantly destabilize the protein structure and disrupt the secondary structures, especially in segment 2. The deleterious effects of mutations in segment 1 are possibly not from destabilization but from other factors such as the change in phosphorylation as suggested by post-translational modification (PTM) studies. This is the first-ever study of ADAMTS3 gene polymorphism, and the predicted nsSNPs in ADAMST3, some of which have not been reported yet in patients, will serve for diagnostic purposes and further therapeutic implications in Hennekam syndrome, contributing to better diagnosis and treatment.


Angiotensin converting enzyme inhibitor as an additive treatment after successful balloon dilation of a critical pulmonary valve stenosis.
A 2 days old, 2.7 kg heavy baby boy with critical pulmonary stenosis, underwent successful balloon dilation. After the uneventful procedure, he remained oxygen dependent. The baby was given oral angiotensin converting enzyme inhibitor (ACE inhibitor), instead of an infusion of alpha blocker. Within few hours, in the afternoon of the same day after administration of ACE Inhibitor, the baby could be weaned off oxygen, maintaining on room air, oxygen saturation between 87% and 92%. At follow-up, two months later, his saturation was 99% on room air. We believe that some neonates with critical pulmonary valve stenosis who remain oxygen dependent despite successful balloon dilation, could benefit from such management.


Engineered heterologous FPP synthases-mediated Z,E-FPP synthesis in E. coli.
Production of Z-type farnesyl diphosphate (FPP) has not been reported in Escherichia coli. Here we present the fusion enzyme (ILRv) of E. coli E,E-FPP synthase (IspA) and Mycobacterium tuberculosis Z,E-FPP synthase (Rv1086), which can produce primarily Z,E-FPP rather than E,E-FPP, the predominant stereoisomer found in most organisms. Z,E-farnesol (FOH) was produced from E. coli harboring the bottom portion of the MVA pathway and the fusion FPP synthase (ILRv) at a titer of 115.6 mg/L in 2YT medium containing 1% (v/v) glycerol as a carbon source and 5 mM mevalonate. The Z,E-FOH production was improved by 15-fold, compared with 7.7 mg/L obtained from the co-overexpression of separate IspA and Rv1086. The Z,E-FPP was not metabolized in native metabolic pathways of E. coli. It would be of interest to produce Z,E-FPP derived sesquiterpenes from recombinant E. coli due to no loss of Z,E-FPP substrate in endogenous metabolism of the host strain.


EZH2 deletion in early mesenchyme compromises postnatal bone microarchitecture and structural integrity and accelerates remodeling.
In this study, we examined the functional importance of EZH2 during skeletal development and homeostasis using the conditional deletion of Ezh2 (Ezh2fl/fl ) in early mesenchyme with the use of a Prrx-1-cre driver mouse (Ezh2+/+). Heterozygous (Ezh2+/-) newborn and 4-wk-old mice exhibited increased skeletal size, growth plate size, and weight when compared to the wild-type control (Ezh2+/+), whereas homozygous deletion of Ezh2 (Ezh2-/-) resulted in skeletal deformities and reduced skeletal size, growth plate size, and weight in newborn and 4-wk-old mice. Ezh2-/- mice exhibited enhanced trabecular patterning. Osteogenic cortical and trabecular bone formation was enhanced in Ezh2+/- and Ezh2-/- animals. Ezh2+/- and Ezh2-/- mice displayed thinner cortical bone and decreased mechanical strength compared to the wild-type control. Differences in cortical bone thickness were attributed to an increased number of osteoclasts, corresponding with elevated levels of the bone turnover markers cross-linked C-telopeptide-1 and tartrate-resistant acid phosphatase, detected within serum. Moreover, Ezh2+/- mice displayed increased osteoclastogenic potential coinciding with an upregulation of Rankl and M-csf expression by mesenchymal stem cells (MSCs). MSCs isolated from Ezh2+/- mice also exhibited increased trilineage potential compared with wild-type bone marrow stromal/stem cells (BMSCs). Gene expression studies confirmed the upregulation of known Ezh2 target genes in Ezh2-/- bone tissue, many of which are involved in Wnt/BMP signaling as promoters of osteogenesis and inhibitors of adipogenesis. In summary, EZH2 appears to be an important orchestrator of skeletal development, postnatal bone remodelling and BMSC fate determination in vitro and in vivo-Hemming, S., Cakouros, D., Codrington, J., Vandyke, K., Arthur, A., Zannettino, A., Gronthos, S. EZH2 deletion in early mesenchyme compromises postnatal bone microarchitecture and structural integrity and accelerates remodeling.


Spontaneously generated large adipose flaps in vivo tissue engineering chambers.
Previous experiments using our in vivo tissue engineering chamber (TEC) model demonstrated that adipose flap was spontaneously generated without the need for adipocyte or stem cell implantation. The purposes of the present study are to clarify 1) the reproducibility of this method to create adipose flaps, 2) the time-course of adipogenesis, and 3) the long-term stability of the adipose flap generated. The chambers that afforded a protected space for tissue growth were implanted into the groins of rabbits. A vascular pedicle as the vascular source of newly formed tissue, a collagen sponge as a scaffold, and platelet-rich plasma (PRP) and fibroblast growth factor (bFGF) as growth factors were contained within the chamber. There were three experimental groups according to the implantation period of the chamber; Group 4 w, Group 8 w, and Group 12 w (n = 5 in each group). The percent volumes of the combined adipose/pedicle tissue compared with the total volume of the generated tissue were 14.8% (0.437 cm3/2.96 cm3), 47% (0.87 cm3/1.85 cm3) and 80% (1.82 cm3/2.27 cm3) in Groups 4 w, 8 w, and 12 w, respectively. When a 12-week adipose flap was transferred outside the chamber on its vascular pedicle and retained for a further five months, it became more like mature adipose tissue and had increased fat density. Adipose flaps were spontaneously generated in vivo in TECs at 12 weeks with reproducibility and showed long-term stability outside the chamber following pedicle transfer. The tissue-engineered adipose flap will contribute to breast reconstruction and augmentation without donor-site morbidity.


Photosensitivity syndrome brings to light a new transcription-coupled DNA repair cofactor.
Three teams have applied whole-exome and proteome methods to identify a new cofactor of human RNA polymerase II that is required for the recovery of transcription on damaged templates. The identification of this new factor raises questions about the causal relationships between molecular mechanisms of transcription regulation and excision repair and developmental and neurological disease and nonmalignant skin photosensitivity.


Short-term toxicity of hexavalent-chromium to epipsammic diatoms of a microtidal estuary (Río de la Plata): responses from the individual cell to the community structure.
Diatoms are an integral and often dominant component of the benthic microalgal assemblage in estuarine and shallow coastal environments. Different toxic substances discharged into these ecosystems persist in the water, sediments, and biota for long periods. Among these pernicious agents, the toxicity in diatoms by metal is linked to different steps in the transmembrane and internal movements of the toxicant, causing perturbations in the normal structural and functional cellular components. These changes constitute an early, nontaxonomic warning signal that could potentially serve as an indicator of this type of pollution. The aim of this work was to study the environment-reflecting short-term responses at different levels of organization of epipsammic diatoms from the Río de la Plata estuary, Argentina that had been exposed to hexavalent chromium within experimental microcosms. To this end we monitored: (i) changes in the proportion of the diatoms in relation to other algal groups at the biofilm community level; (ii) shifts in species composition at the diatom-assemblage level; (iii) projected changes in the densities of the most representative species at the population level through comparison of relative growth rates and generation times; and (iv) the cytological changes at the cellular and subcellular levels as indicated by the appearance of teratological effects on individuals and nuclear alterations. The epipsammic biofilms were exposed for 96 h to chromium at a concentration similar to that measured in highly impacted sites along the coast (80 μg L⁻¹). Chromium pollution, at this concentration and short exposure time did not affect the algal biomass and density of these mature biofilms. The biofilm composition, however, did change, as reflected in a decline in cyanophytes and an increment in the proportions of diatoms and chlorophytes; with Hippodonta hungarica, Navicula novaesiberica, Nitzschia palea, and Sellaphora pupula being the most frequent and abundant species. The most notable shifts related to chromium exposure were a decrease in the relative abundance of H. hungarica and a significant increase in the proportion of N. palea. Moreover, the species analyzed in the treatment microcosms showed higher growth rates than in the controls--N. palea grew faster, while H. hungarica replicated more slowly. The total nuclear abnormalities--as recorded in Fallacia pygmaea and N. novaesiberica--were significantly higher in the treatment microcosms; whereas in N. palea, the dominant species in treatment microcosms, neither nuclear alterations nor abnormal frustules were observed.


Diatom-assisted biomicroreactor targeting the complete removal of perfluorinated compounds.
Persistent perfluorinated compounds (PFCs) have been recognized as a global environmental issue. Developing methods without leading to additional burden in nature will be essential for PFCs removal. Herein, we functionalized iron nanoparticles on living diatom (Dt) to efficiently enable the Fenton reaction and reactive oxygen species (ROS) production. Iron nanoparticles at the surface of living diatom act as promising catalytic agents to trigger OH radical generation from H2O2. Dt plays dual roles: i) as solid support for effective adsorption, and ii) it supplies oxygen and inherently produces ROS under stress conditions, which improves removal efficiency of PFCs. We also demonstrated its reusability by simple magnetic separation and 85% of decomposition efficiency could still be achieved. This newly developed diatom-assisted bioremediation strategy enables green and efficient PFC decomposition and shall be readily applicable to other persistent pollutants.


Metastatic melanoma of the nasal cavity in a patient with oculocutaneous albinism.
The nasal cavity is a rare location for primary malignant melanoma, borne out by the few cases reported in the literature since 1940. Rarest of all is nasal melanoma in a patient with oculocutaneous albinism. An albino subject, aged 33, was referred to us with this diagnosis. Because of the numerous metastases in the liver and left lung, we did not advise radical surgical intervention and, despite hyperfractionated high dose radiotherapy and chemo-immunotherapy, the advanced stage of disease caused the death of the patient within a year. We have reviewed the diagnostic, clinical and therapeutic aspects, and the literature on melanomas of the nasal cavity in albino subjects. We performed a Medline literature search, examining only 'extensive' papers and excluding abstracts or case reports presenting poor data.


Combined effects of increased O3 and reduced NO2 concentrations on short-term air pollution health risks in Hong Kong.
The reduction of NOx emissions in a VOC-limited region can lead to an increase of the local O3 concentration. An evaluation of the net health effects of such pollutant changes is therefore important to ascertain whether the emission control measures effectively improve the overall protection of public health. In this study, we use a short-term health risk (added health risk or AR) model developed for the multi-pollutant air quality health index (AQHI) in Hong Kong to examine the overall health impacts of these pollutant changes. We first investigate AR changes associated with NO2 and O3 changes, followed by those associated with changes in all four AQHI pollutants (NO2, O3, SO2, and particulate matter (PM)). Our results show that for the combined health effects of NO2 and O3 changes, there is a significant reduction in AR in urban areas with dense traffic, but no statistically significant changes in other less urbanized areas. The increase in estimated AR for higher O3 concentrations is offset by a decrease in the estimated AR for lower NO2 concentrations. In areas with dense traffic, the reduction in AR as a result of decreased NO2 is substantially larger than the increase in AR associated with increased O3. When additionally accounting for the change in ambient SO2 and PM, we found a statistically significant reduction in total AR everywhere in Hong Kong. Our results show that the emission control measures resulting in NO2, SO2, and PM reductions over the past decade have effectively reduced the AR over Hong Kong, even though these control measures may have partially contributed to an increase in O3 concentrations. Hence, efforts to reduce NOx, SO2, and PM should be continued.


Expression of cell adhesion molecules and their beta1 and beta2 integrin ligands in human liver peliosis.
The expression of the following cell adhesion molecules and their beta1 and beta2 integrin ligands was investigated in the liver tissue from 3 patients with non-bacillar peliosis using light and electron microscope immunohistochemistry: intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, platelet endothelial cell adhesion molecule-1 (PECAM-1), leukocyte function-associated antigen-1 (LFA-1), macrophage antigen-1 (Mac-1), and very late antigen-4 (VLA-4). We found a parallel enhancement of the adhesion molecules expression in the dilated sinusoids and cavities in all 3 cases with peliosis. Mononuclear blood cells were detected in the sinusoids and sometimes perisinusoidally. These cells were mainly ICAM-1-, LFA-1-, and VLA-4-positive. At the ultrastructural level, ICAM-1-positive immune deposits were observed on the membrane of sinusoidal endothelial cells, Kupffer cells, and hepatocytes. The expression of cell adhesion molecules on liver sinusoids in peliosis is probably triggered by factors released from damaged endothelial cells and hepatocytes. The prevalence of the ICAM-1/LFA-1 and VCAM-1/VLA-4 patterns of mononuclear blood cell/sinusoidal cell interactions could support the macrophage-induced or lymphocyte-induced type of liver injury. PECAM-1 was also included in the non-specific immune response in peliosis. The presence of erythrostasis or thrombosis in liver sinusoids could participate in the induction of adhesion molecule expression in peliosis.


HPA system regulation and adult attachment anxiety: individual differences in reactive and awakening cortisol.
Early life experiences can influence hypothalamus-pituitary-adrenal (HPA) axis regulation in adulthood, in both animals and humans. In humans, they have also been shown to influence adult attachment styles. However, the relationship between adult attachment styles and HPA axis regulation is largely unexplored. The present study investigated the relationship among varying levels of attachment anxiety and avoidance with both the cortisol response to acute stress (CRS) and the cortisol response to awakening (CRA) in 48 adult women. Attachment-unrelated stress was induced by a laboratory stress task. Saliva for free cortisol assessment was sampled before and after the stress task in the laboratory and at home on 2 consecutive days in the morning after awakening. We found that attachment anxiety but not attachment avoidance was associated with cortisol measures. Attachment anxiety was positively correlated with CRS and negatively with CRA. Finally, the two cortisol parameters were negatively associated with one another. The results are discussed with respect to (1) recent findings suggesting that the HPA system and hippocampus are programmed during critical development periods, establishing a certain trajectory of physiological responsiveness throughout life, and (2) a model that links development of the hippocampus with self development.


Patient Reported vs Claims Based Measures of Health for Modeling Life Expectancy in Men with Prostate Cancer.
Life expectancy has become a core consideration in prostate cancer care. While multiple prediction tools exist to support decision making, their discriminative ability remains modest, which hampers usage and utility. We examined whether combining patient reported and claims based health measures into prediction models improves performance. Using SEER (Surveillance, Epidemiology, and End Results)-CAHPS (Consumer Assessment of Healthcare Providers and Systems) we identified men 65 years old or older diagnosed with prostate cancer from 2004 to 2013 and extracted 4 types of data, including demographics, cancer information, claims based health measures and patient reported health measures. Next, we compared the performance of 5 nested competing risk regression models for other cause mortality. Additionally, we assessed whether adding new health measures to established prediction models improved discriminative ability. Among 3,240 cases 246 (7.6%) died of prostate cancer while 631 (19.5%) died of other causes. The National Cancer Institute Comorbidity Index score was associated but weakly correlated with patient reported overall health (p <0.001, r=0.21). For predicting other cause mortality the 10-year area under the receiver operating characteristic curve improved from 0.721 (demographics only) to 0.755 with cancer information and to 0.777 and 0.812 when adding claims based and patient reported health measures, respectively. The full model generated the highest value of 0.820. Models based on existing tools also improved in their performance with the incorporation of new data types as predictor variables (p <0.001). Prediction models for life expectancy that combine patient reported and claims based health measures outperform models that incorporate these measures separately. However, given the modest degree of improvement, the implementation of life expectancy tools should balance model performance with data availability and fidelity.


Cost-effectiveness analysis in relation to budgetary constraints and reallocative restrictions.
Present cost-effectiveness analyses (CEAs) provide not all information necessary for decision-making. One of the factors that hamper decision-making is the difficulty in reallocating resources to new technologies. In a CEA, the incremental costs and incremental benefits of a new technology are calculated. In this article we focus on the incremental cost side. The underlying assumption in socio-economic evaluation is that resources from the substituted alternatives can be used to finance the new technology. In practice, however, not all resources are becoming available to introduce the alternative. The budgets in health care are rather fixed and shifting from one alternative to another or from one sector to another is often impossible. Even within a budget, the personnel and material resources are usually not entirely usable for the new technology, and sometimes not at all. Therefore, the present CEA outcomes might overestimate the cost-effectiveness in practice, which might influence implementation of a new technology. To optimise the usefulness of economic evaluation for health care decision-making by correcting the incremental costs of a new technology for the possible limitations in reallocating resources and adjusting budgets in health care. Case Research. Literature, data from two completed CEAs and interviews with decision makers in the hospital setting. Case 1: The combined outpatient and home-treatment of psoriasis--In a CEA it was calculated that the new technology lead to much lower cost, given the same effects. The direct costs of this technology comprise personnel, material and capacity costs. Personnel and capacity are inflexible with regard to reallocation, at least in the short term. Considering these reallocative restrictions results show that the cost-savings of the combined treatment are in the short run significantly smaller than in the long run: 694 versus 6.058, respectively. Therefore, the anticipated savings, estimated are not realistic for decision makers with a short time horizon. The short-term savings amount to only 11% of the anticipated savings in the long run. Nevertheless, the combined treatment remains a cost-effective treatment. Analysing the budgetary constraints resulted in the finding that the substitution of the in-hospital treatment by the combined treatment has taken place without negative financial consequences for the hospital. Case 2: The ground bound mobile medical team--Economic arguments to implement the ground bound mobile medical team (MMT) are undecided. With respect to the budgetary constraints we find that the budget for the trauma centre is conditional upon the deployment of the ground bound MMT. Moreover, the cost of the ground bound MMT is a relatively small part of the budget for the trauma centre and therefore no hurdle to implement. On the basis of these findings we conclude that limitations in reallocating resources and adjusting budgets in health care may hamper the usefulness of economic evaluation for decision-making. Researching the extent of these limitations provides, together with the CEA, better information on which the decision whether a new technology should be implemented and what the expected welfare gains from such an implementation might be can be made. For this a set of checklists is developed.


Human influences shape the first spatially explicit national estimate of urban unowned cat abundance.
Globally, unowned cats are a common element of urban landscapes, and the focus of diverse fields of study due to welfare, conservation and public health concerns. However, their abundance and distribution are poorly understood at large spatial scales. Here, we use an Integrated Abundance Model to counter biases that are inherent in public records of unowned cat sightings to assess important drivers of their abundance from 162 sites across five urban towns and cities in England. We demonstrate that deprivation indices and human population densities contribute to the number of unowned cats. We provide the first spatially explicit estimates of expected distributions and abundance of unowned cats across a national scale and estimate the total UK urban unowned cat population to be 247,429 (95% credible interval: 157,153 to 365,793). Our results provide a new baseline and approach for studies on unowned cats and links to the importance of human-mediated effects.


A case of a giant mucocoele of the appendiceal stump presented with a palpable mass in the right thigh: pre-operative diagnosis based on characteristic multidetector CT findings.
The pre-operative diagnosis of a mucocoele of the appendiceal stump (MAS) may be difficult owing to rarity and non-specific clinical presentation. However, a pre-operative diagnosis of a MAS is important to prevent widespread dissemination by inadvertent spillage of mucous contents. We describe a case of a MAS presenting with a palpable mass in the right thigh in which a pre-operative diagnosis was made by characteristic multidetector CT (MDCT) findings.


Dysgerminoma of the ovary: a report on 29 patients.
Twenty nine patients with pure dysgerminoma of the ovary were referred to the Institute of Radiology of the University of Florence between 1960 and 1983. Twenty six patients received radiation therapy after surgery; three cases, classified as Stage IA, were not submitted to postoperative radiation therapy. Five patients relapsed 2 to 16 months after initial surgery, and three of them died because of their tumours. Sites of relapse were found to be outside the treated volume in four out of these five patients. The overall survival rate for this series is 90%. The survival rate seems to depend not only on the stage of the disease, but also on initial accurate staging and appropriate therapy. Criteria for selecting patients from whom post-operative radiotherapy may be withheld are discussed.


Contractile properties of skinned preparations from ischaemic canine myocardium and coronary arteries.
The influence of prolonged ischaemia on the regulation of contraction in the myocardium and in the smooth muscle of coronary arteries was investigated. Chemically skinned preparations were used which enabled the contraction to be studied with the environment of the contractile filaments controlled. Myocardial ischaemia was produced in anesthetized adult beagle dogs by occlusion of the left anterior descending artery for 3 h and followed by 30 min reperfusion. Myocardial tissue and segments from coronary arteries were obtained from the ischaemic infarcted wall region ("in vivo ischaemic") and compared with control preparations from perfused coronary arteries and from the free wall of the left ventricle. Coronary and myocardial preparations were also obtained from the heart after a 3 h period in vitro under anoxic conditions at 37 degrees C ("in vitro ischaemic") simulating a state of extreme ischaemia. Control myocardial fibres were fully relaxed at pCa (-log-[Ca2+]) 9 and developed 24 +/- 5% (n = 7) of maximum force at intermediate calcium concentration (pCa 5.5). In contrast, the in vivo and in vitro ischaemic preparations produced force at pCa 9 (28 +/- 13 and 39 +/- 8%, respectively, n = 5 and 7) and showed an increased force development at pCa 5.5 (53 +/- 11 and 75 +/- 5%). The in vivo and in vitro ischaemic coronary arteries relaxed more slowly following calcium removal than control vessels. The in vitro ischaemic vascular preparations developed active force at pCa 9 and showed increased levels of myosin light chain phosphorylation and reduced phosphatase activity.(ABSTRACT TRUNCATED AT 250 WORDS)