Steroid hormonal regulation of proliferative, p53 tumor suppressor, and apoptotic responses of sheep ovarian surface epithelial cells.
Ovarian surface epithelial cells have been implicated in the genesis of common ovarian cancers. The integrity of DNA of ovarian surface epithelial cells contiguous with the ovulatory stigma becomes compromised during the rupture process; most cells degenerate by apoptosis, however some, bearing sublethal lesions, persist along the margins of ovulated follicles. Clonal expansion of a genetically-damaged surface epithelial cell (i.e. with unrepaired DNA, but not committed to death) can presumably give rise to ovarian carcinoma. It was hypothesized that estradiol and progesterone regulate ovarian surface epithelial cell-cycle dynamics associated with folliculo-luteal transitions and ovulatory wound repair/remodeling. Progesterone up-regulated the tumor suppressor p53 and inhibited baseline and estradiol-stimulated proliferation of cultured sheep ovarian surface epithelial cells. Anti/mitotic responses to steroid hormones were transcriptionally- and receptor-dependent. Rates of apoptosis (DNA fragmentation) were unaffected by progesterone. High concentrations of estradiol, via a nongenomic (perhaps antioxidant) mechanism, suppressed basal and H(2)O(2)-induced apoptosis. We suggest that, progesterone serves to inhibit proliferation of ovarian surface epithelial cells throughout the luteal phase--providing the time (growth arrest) required to correct any metabolic disturbances to DNA that are perpetrated as an inevitable by-product of the ovulatory process. With luteolysis and dominance of an estrogenic preovulatory follicle the ovarian surface epithelium is then regenerated. Thus, it is conceivable that perturbations to the steroid hormonal milieu of ovarian cycles could be a predisposing factor for cancerous transformation of an ovarian surface epithelial cell.


Laparoendoscopic single site live donor nephrectomy: initial experience.
We present our initial experience in 40 patients undergoing laparoendoscopic single site donor nephrectomy. We prospectively collected data on 40 consecutive patients. A single access GelPOINT™ device was inserted into the abdomen through a 4 to 5 cm periumbilical incision. We used a bariatric camera with a right angle attachment for the light cord to maximize triangulation. Parameters analyzed included warm ischemia time, operative time, estimated blood loss, visual analog pain score, time to recipient creatinine less than 3 mg/dl, and recipient creatinine at discharge home, and 3 and 6 months. A total of 38 left and 2 right donor nephrectomies were performed. Complete laparoendoscopic single site donor nephrectomy was successful in 38 cases. One left and 1 right case were converted to a hand assisted approach. Average ± SD body mass index was 26.1 ± 5.2 kg/m(2). Mean operative time to allograft extraction was 93.5 ± 27.5 minutes and mean total operative time was 166.7 ± 33.8 minutes. Average estimated blood loss was 106.7 ± 93.5 cc. Mean warm ischemia time was 3.96 ± 0.72 minutes. Mean hospital stay was 1.77 ± 0.43 days and median time to recipient creatinine less than 3.0 mg/dl was 54.2 ± 110.3 hours. Mean recipient creatinine at discharge home, and at 3 and 6 months was 1.48 ± 0.67, 1.29 ± 0.38 and 1.19 ± 0.34 mg/dl, respectively. Complications included hyponatremia in 1 patient, wound infection in 1, and a grade III laceration in an allograft that was sustained during extraction. Our initial experience with laparoendoscopic single site donor nephrectomy is encouraging. This approach to kidney donation without an extra-umbilical incision could become particularly relevant to minimize morbidity in young, healthy organ donors.


Experiences of a High-Risk Population with Prenatal Hemoglobinopathy Carrier Screening in a Primary Care Setting: a Qualitative Study.
Carrier screening for hemoglobinopathies (HbPs; sickle cell disease and thalassemia) aims to facilitate autonomous reproductive decision-making. In the absence of a Dutch national HbP carrier screening program, some primary care midwives offer screening on an ad hoc basis. This qualitative descriptive study explores how pregnant women perceive an offer of HbP carrier screening by their midwife. Semi-structured interviews (n = 26) were conducted with pregnant women at risk of being a HbP carrier, and whom were offered screening at their booking appointment in one of two midwifery practices in Amsterdam. The results showed that half of the respondents were familiar with HbPs. Generally, women perceived the offer of HbP carrier screening as positive, and most women (n = 19) accepted screening. Seven declined, of whom two already knew their carrier status. Important reasons to accept screening were to obtain knowledge about their own carrier status and health of their unborn child, and the ease of the procedure. A multistep process of decision-making was observed, as many women did not give follow-up testing (e.g. partner, invasive diagnostics) much consideration while deciding on accepting or declining HbP screening. Women experienced information overload, and preferred receiving the information at a different moment (e.g. before the intake by a leaflet, or preconceptionally). In conclusion, while prenatal HbP carrier screening is perceived as positive, informed decision-making seems to be suboptimal, and both the content and timing of the information provided needs improvement.


Isolation and identification of a megalocytivirus strain (SKIV-TJ) from cultured spotted knifejaw (Oplegnathus punctatus) in China and its pathogenicity analysis.
The spotted knifejaw (Oplegnathus punctatus) has recently emerged as a highly economically significant farmed fish in China. However, due to increasing environmental pollution and breeding density, a range of infectious diseases, including the iridovirus pathogen, have begun to spread widely. In this study, we isolated and identified a strain of Megalocytivirus, SKIV-TJ, from cultured spotted knifejaw in Tianjin, China. We observed significant cytopathic effects (CPE) in SKIV-TJ-infected spotted knifejaw brain (SKB) cells, and electron microscopy showed numerous virus particles in the cytoplasm of SKB cells 6 days post-infection. The annotated complete genome of SKIV-TJ (GenBank accession number ON075463) contained 112,489 bp and 132 open reading frames. Based on the multigene association evolutionary tree using 26 iridovirus core genes, SKIV-TJ was found to be most closely related to Rock bream iridovirus (RBIV). Cumulative mortality of spotted knifejaw infected with SKIV-TJ reached 100% by day 9. A transcriptomic analysis were conducted and a total of 5517 differentially expressed genes were identified, including 2757 upregulated genes and 2760 downregulated genes. The upregulated genes were associated with viral infection and immune signaling pathways. Our findings provide a valuable genetic resource and a deeper understanding of the immune response to SKIV infection in spotted knifejaw.


Columbin inhibits cholesterol uptake in bloodstream forms of Trypanosoma brucei-A possible trypanocidal mechanism.
The diterpenoid furanolactone (columbin) from Aristolochia albida inhibited growth of culture forms of Trypanosoma brucei. In vitro analysis of the compound at 5-250 microg/ml showed complete lysis of the parasites within 10-20 minutes post incubation. At 50 microg/ml, columbin killed about 50% of the parasites which initially appeared swollen under phase contrast microscopy. Also the total amount of cholesterol diminished dose-dependently in the presence of 10-100 microg/ml of columbin after a 3-day incubation period. In vivo analysis of the compound in T. brucei-infected mice revealed that 25 mg/kg administered for 3 consecutive days, completely cleared the parasites from the peripheral circulation. However, columbin could not clear parasites in the cerebrospinal fluid.


Neuropeptide Y activates phosphorylation of ERK and STAT3 in stromal vascular cells from brown adipose tissue, but fails to affect thermogenic function of brown adipocytes.
The thermogenic function of brown adipose tissue (BAT) is increased by norepinephrine (NE) released from sympathetic nerve endings, but the roles of NPY released along with NE are poorly elucidated. Here, we examined effect of NPY on basal and NE-enhanced thermogenesis in isolated brown adipocytes that express Y1 and Y5 receptor mRNA. Treatment of cells with NPY did not influence the basal and NE-enhanced rates of oxygen consumption and cAMP accumulation. Treatment with NPY also failed to induce ERK (Thr202/Tyr204) phosphorylation in the brown adipocytes. In contrast, treatment with NPY increased ERK phosphorylation in cultured stromal vascular cells from the BAT that express Y1 receptor mRNA. In the latter treatment with NPY also increased STAT3 (Ser727) phosphorylation. These results suggest that NPY mainly acts on stromal vascular cells in BAT and plays roles in the regulation of their gene transcription through ERK and STAT3 pathways, while NPY does not affect the thermogenic function of brown adipocytes.


Possible mediators of the writhing response induced by acetic acid or phenylbenzoquinone in mice.
1. Despite widespread use of the writhing response to phenylbenzoquinone or acetic acid injection in mice as a screen for analgesic activity, possible mediators of this response remain unidentified. 2. In the present experiments both in vivo and in vitro techniques have been used in an attempt to identify these mediators. 3. Acetic acid-induced writhing was unaffected by pretreatment with mepyramine, methysergide, disodium cromoglycate or cimetidine. 4. Phenylbenzoquinone-induced writhing was partially blocked by pretreatment with mepyramine or other antihistamines. 5. Using guinea-pig isolated ileum and rat fundus preparations as in vitro assay systems, no significant differences were detected in histamine, serotonin, or prostaglandin content of peritoneal fluid from writhing and control mice. 6. Acetylcholine levels were at the limit of detection in these samples, and there was no evidence of kinin release. 7. Thus the mediators involved in the writhing response remain undefined.


Clinicians poorly assess health literacy-related readiness for transition to adult care in adolescents with inflammatory bowel disease.
To prepare for the transition from pediatric to adult-oriented health care systems, adolescents must develop the ability to obtain, process, and understand basic health information; make appropriate health decisions; and interact effectively with health care professionals. However, physicians use subjective methods to determine patients' readiness for this transition. We investigated health care literacy-related readiness for transition of children and adolescents with inflammatory bowel disease (IBD) to identify determinants and compare actual levels with clinicians' opinions. The study included 74 pediatric patients with IBD ≥10 years old who were recruited from a pediatric hospital-based clinic. We evaluated their functional and interactive health literacy and recorded clinicians' perceptions of literacy and readiness for transition among pediatric patients. Relationships between health literacy measures, demographic variables, and clinician perceptions were determined. Health literacy-related readiness for transition was observed in 11% of the patients analyzed. However, clinicians found 47% of the cohort ready for the transition, on the basis of literacy standards. Health literacy-related readiness for transition was associated with older age (P < .01), white race (P = .03), and low income (P < .02). Agreement was poor between measures-defined and clinician-defined levels of health literacy-related readiness for transition (P = .18). Clinicians inadequately judge the health literacy-related readiness for transition to adult care of pediatric IBD patients. Improved awareness of health literacy issues among adolescents with IBD is needed among health care providers and health care systems.


Diameter of the cochlear nerve in endolymphatic hydrops: implications for the etiology of hearing loss in Ménière's disease.
Endolymphatic hydrops (ELH) is an important histopathological hallmark of Ménière's disease. Experimental data from human temporal bones as well as animal models of the disorder have generally failed to determine the mechanism by which ELH or related pathology causes hearing loss. Hair cell and spiral ganglion cell counts in both human and animal case studies have not, for the most part, shown severe enough deterioration to explain associated severe sensorineural hearing loss. However a limited number of detailed ultrastructural studies have demonstrated significant reductions in dendritic innervation densities, raising the possibility that neurotoxicity plays an important role in the pathology of Ménière's disease (MD) as well as experimental endolymphatic hydrops (ELH). This study tests the hypothesis that neurotoxicity is an important primary mediator of injury to the hydropic ear and is reflected in measurable deterioration of the cochlear nerve in the animal model of ELH. This study also explores the previously presented hypothesis that cochlear injury in ELH is mediated through the actions of nitric oxide (NO) by evaluating whether hearing loss or various measures of cochlear damage can be ameliorated by administration of an agent that limits excess production of NO. Part one of the project involves the surgical induction of endolymphatic hydrops and correlation of long term hearing loss with histological parameters of ELH severity as well as cochlear nerve and eighth cranial nerve diameter measurements. In part two, aminoguanidine is administered orally to a separate set of hydropic animals in an attempt to limit cochlear injury presumably mediated by NO. Guinea pigs are subjected to surgical induction of unilateral endolymphatic hydrops after establishing baseline ABR thresholds at 2, 4, 8, 16, and 32 kHz. Threshold shifts are established prior to sacrifice at 4 to 6 months and temporal bones processed for light microscopy. Measurements of cochlear nerve and eighth cranial nerve maximal diameters as well as average maximal diameters are carried out and correlated to hearing loss and a semi-quantitative measure of hydrops severity. The identical experiments are carried out in animals treated with aminoguanidine, an inhibitor of inducible nitric oxide synthase. : The mean maximal diameter (n = 14) of the hydropic cochlear nerve was significantly reduced (432.14 +/- 43.18 vs. 479.28 +/- 49.22 microns, P = .0025) as compared to the control nerve. This was also seen in measures of the eighth cranial nerve (855.71 +/- 108.82 vs. 929 +/- 81.53 microns, P = 0.0003). Correlation studies failed to show correlation between hydrops severity and a cochlear nerve deterioration index (r = -0.0614, P = .8348). Similarly, hearing loss severity failed to correlate with cochlear nerve deterioration (r = 0.1300, P = .6577). There was a significant correlation between hearing loss and hydrops severity (r = 0.6148, P = .0193). Aminoguanidine treated animals (n = 5) also sustained nerve deterioration to the same degree as non-treated animals and there appeared to be no protective effect (at the dosage administered) against ELH related hearing loss, hydrops formation, or nerve deterioration. ELH results in significant deterioration of cochlear nerve and eighth cranial nerve maximal diameters in the guinea pig model. These findings are in accord with previous studies which detected ultrastructural evidence of dendritic damage and indicate that neural injury is of sufficient severity to result in light microscopic evidence of cochlear nerve and eighth cranial nerve deterioration. These data support the concept that the principle pathological insult in ELH is a form of neurotoxicity, especially in light of previous studies which indicate relative preservation of hair cells at similar points in time. The lack of correlation between the severity of hydrops and nerve deterioration suggests that nerve deterioration is independent of hydrops severity.


[The effect of emotional stress on the hormonal status indices, the level of cyclic nucleotides and the content of beta 2-microglobulin in the blood and thymic tissue during the use of a synthetic analog of thyroliberin].
After experiencing a conflict situation once or daily for 5 days, rats were divided into a group resistant to stress and a group predisposed to stress according to the post-stress involution of the thymus. Changes in biochemical values were revealed in emotional stress. Significant drop in the blood insulin level, a high cAMP/cGMP ratio level, and reduction of the beta 2-microglobulin level and the level of circulating immune complexes were found. The preparation PR-546 caused an increase of the insulin level in intact and experimental rats, which, however, did not lead to diminution of the stress reaction.


Active travel to work and cardiovascular risk factors in the United Kingdom.
Increasing active travel (walking, cycling, public transport) is increasingly seen as integral to strategies to raise physical activity levels. This study examined (1) sociodemographic correlates of active travel to work and (2) associations between active travel and cardiovascular risk factors in the United Kingdom (UK). Data come from Understanding Society, a nationally representative survey of UK residents in 2009/2011, analyzed in 2012. Multinomial logistic regression assessed associations between sociodemographic factors and mode of transport to work. Linear and logistic regression was used to examine associations between mode of travel and overweight/obesity, and having hypertension or diabetes. A total of 69% of participants traveled to work using private transport, with public transport, walking, and cycling used by 16%, 12%, and 3%, respectively. Use of any active travel was more likely in participants living in London. Black participants were more likely to walk (AOR=1.41, 95% CI=1.08, 1.84) or take public transport (AOR=2.34, 95% CI=1.88, 2.90) to work than whites. Using public transport, walking, or cycling to work was associated with a lower likelihood of being overweight (AOR=0.80, 95% CI=0.54, 0.88 for walking). Walking or cycling was associated with a lower likelihood of having diabetes, and walking was associated with a lower likelihood of having hypertension than private transport (AOR=0.83, 95% CI=0.71, 0.97). There are wide variations in the mode of travel to work across regions and sociodemographic groups in the UK. The protective association between active travel and cardiovascular risk demonstrated in this nationally representative study adds to growing evidence that concerted policy focus in this area may benefit population health.


DNA Repair and Chromosomal Translocations.
The balance between DNA damage, especially double strand breaks, and DNA damage repair is a critical determinant of chromosomal translocation frequency. The non-homologous end-joining repair (NHEJ) pathways seem to play the major role in the generation of chromosomal translocations. The "landscape" of chromosomal translocation identified in malignancies is largely due to selection processes which operate on the growth advantages conveyed to the cells by the functional consequences of chromosomal translocations (i.e., oncogenic fusion proteins and overexpression of oncogenes, both compromising tumor suppressor gene functions). Newer studies have shown that there is an abundance of local rearrangements in many tumors, like small deletions and inversions. A better understanding of the interplay between DNA repair mechanisms and the generation of tumorigenic translocations will, among many other things, depend on an improved understanding of DNA repair mechanisms and their interplay with chromatin and the 3D organization of the interphase nucleus.


Fluorescence kinetics study of twice laser irradiation based HpD-PDT for nonmelanoma skin cancer.
Hematoporphyrine injection (HpD)-based photodynamic therapy (HpD-PDT) has emerged as a promising cancer therapy. However, its tumor-targeting ability and metabolokinetics in nonmelanoma skin cancer (NMSC) have not been well explored. Importantly, photodynamic diagnosis is widely used for cancer lesion assessment and positioning to ensure effective therapy, while the photosensitizer metabolic kinetics study is utilized for biosafety assessment and light-protection instruction. These are particularly important for the optimization of therapeutic parameters. In the present study, NMSC patients were subjected to twice laser irradiation-based HpD-PDT strategy. Broadly, the study aimed to assess long-term variations in fluorescence (FL) intensity in vivo in NMSC patients after intravenous (i.v.) administration of HpD, and thus obtain information regarding metabolism, biosafety, and light-protection instruction for HpD during the therapy. In vitro experiments were used for the evaluation of absorption and fluorescent characterization of HpD in aqueous solution and cutaneous squamous cell carcinoma (SCC) cells. For in vivo assessment, 20 patients with NMSC, including SCC, basal cell carcinoma (BCC), Bowen disease (BD), extramammary Paget's disease (EMPD), and malignant proliferating tricholemmoma (APT), were recruited, and treated with HpD-PDT. To evaluate the selectivity and pharmacokinetics of HpD in vivo, relative changes in FL intensity for lesional, perilesional, and nonlesional skin of nonmelanoma skin cancer patients, before and after HpD injection, were semiquantitatively analyzed for 1 month, using the FL detection system and Wood's lamp. The absorption and FL spectra were detected and semiquantitatively analyzed in HpD diluted solution and SCC cells after coincubation with HpD. After i.v. administration of HpD in EMPD patients, FL was detected in the skin lesions at 24 hours, and it was characterized by clear edges. Importantly, FL intensity in the skin lesions increased significantly at 48 and 72 hours postinjection, which was suitable for HpD-PDT. After 72 h, it decreased gradually and reached close to the baseline value at 4 weeks postinjection. No severe side effects were observed during HpD injection and the therapy. Urinary tract infection was recorded in one patient (with a previous history of recurrent urinary tract infections) after HpD-PDT, and the patient was cured afterward. Transient light was observed in two patients after HpD-PDT and they soon recovered after therapy. The present study reported a significant increase in FL intensities at 48 and 72 hours after i.v. administration of HpD in patients with nonmelanoma skin cancers, which indicated accumulation of HpD at the cancer site. Importantly, HpD was found to be safe for NMSC patients. After therapy, FL intensities decreased, which indicated expending and metabolization of HpD. Thus, the results of the present study highlighted the suitability of a twice red-light laser irradiation strategy for the application of HpD-PDT in nonmelanoma skin cancer treatment.


Time series prediction of COVID-19 by mutation rate analysis using recurrent neural network-based LSTM model.
SARS-CoV-2, a novel coronavirus mostly known as COVID-19 has created a global pandemic. The world is now immobilized by this infectious RNA virus. As of June 15, already more than 7.9 million people have been infected and 432k people died. This RNA virus has the ability to do the mutation in the human body. Accurate determination of mutation rates is essential to comprehend the evolution of this virus and to determine the risk of emergent infectious disease. This study explores the mutation rate of the whole genomic sequence gathered from the patient's dataset of different countries. The collected dataset is processed to determine the nucleotide mutation and codon mutation separately. Furthermore, based on the size of the dataset, the determined mutation rate is categorized for four different regions: China, Australia, the United States, and the rest of the World. It has been found that a huge amount of Thymine (T) and Adenine (A) are mutated to other nucleotides for all regions, but codons are not frequently mutating like nucleotides. A recurrent neural network-based Long Short Term Memory (LSTM) model has been applied to predict the future mutation rate of this virus. The LSTM model gives Root Mean Square Error (RMSE) of 0.06 in testing and 0.04 in training, which is an optimized value. Using this train and testing process, the nucleotide mutation rate of 400th patient in future time has been predicted. About 0.1% increment in mutation rate is found for mutating of nucleotides from T to C and G, C to G and G to T. While a decrement of 0.1% is seen for mutating of T to A, and A to C. It is found that this model can be used to predict day basis mutation rates if more patient data is available in updated time.


Glucose biosensor based on the immobilization of glucose oxidase on electrochemically synthesized polypyrrole-poly(vinyl sulphonate) composite film by cross-linking with glutaraldehyde.
In this study, a novel amperometric glucose biosensor was developed by immobilizing glucose oxidase (GOX) by cross-linking via glutaraldehyde on electrochemically polymerized polypyrrole-poly(vinyl sulphonate) (PPy-PVS) films on the surface of a platinum (Pt) electrode. Electropolymerization of pyrrole and poly(vinyl sulphonate) on the Pt surface was carried out with an electrochemical cell containing pyrrole and poly(vinyl sulphonate) by cyclic voltammetry between -1.0 and + 2.0 V (vs.Ag/AgCl) at a scan rate of 50 mV/s upon the Pt electrode. The amperometric determination was based on the electrochemical detection of H(2)O(2) generated in enzymatic reaction of glucose. Determination of glucose was carried out by the oxidation of enzymatically produced H(2)O(2) at 0.4 V vs. Ag/AgCl. The effects of pH and temperature were investigated and optimum parameters were found to be 7.5 and 65°C, respectively. The effect of working potential was investigated and optimum potential was determined to be 0.4 V. The operational stability of the enzyme electrode was also studied. The response of the PPy/PVS-GOX glucose biosensor exhibited good reproducibility with a relative standard deviation (RSD) of 2.48%. The glucose biosensor retained 63% of initial activity after 93 days when stored in 0.1 M phosphate buffer solution of pH 7.5 at 4°C. With the low operating potential, the biosensor demonstrated little interference from the possible interferants.


Immune modulation by mesenchymal stem cells.
Mesenchymal stem cells (MSCs) can be derived from various adult tissues with multipotent and self-renewal abilities. The characteristics of presenting no major ethical concerns, having low immunogenicity and possessing immune modulation functions make MSCs promising candidates for stem cell therapies. MSCs could promote inflammation when the immune system is underactivated and restrain inflammation when the immune system is overactivated to avoid self-overattack. These cells express many immune suppressors to switch them from a pro-inflammatory phenotype to an anti-inflammatory phenotype, resulting in immune effector cell suppression and immune suppressor cell activation. We would discuss the mechanisms governing the immune modulation function of these cells in this review, especially the immune-suppressive effects of MSCs.


Spontaneous resolution of unilateral vitreomacular traction.
Vitreomacular traction (VMT) caused visual symptoms in two healthy young adults but spontaneously resolved within four weeks without any sequelae. Optical coherence tomography (OCT) and fundus photographs proved vital in documenting the rare complete resolution of VMT. It is prudent to monitor for spontaneous resolution of VMT in young healthy adults.


DNA double-strand breaks induce H2Ax phosphorylation domains in a contact-dependent manner.
Efficient repair of DNA double-strand breaks (DSBs) requires a coordinated DNA Damage Response (DDR), which includes phosphorylation of histone H2Ax, forming γH2Ax. This histone modification spreads beyond the DSB into neighboring chromatin, generating a DDR platform that protects against end disassociation and degradation, minimizing chromosomal rearrangements. However, mechanisms that determine the breadth and intensity of γH2Ax domains remain unclear. Here, we show that chromosomal contacts of a DSB site are the primary determinants for γH2Ax landscapes. DSBs that disrupt a topological border permit extension of γH2Ax domains into both adjacent compartments. In contrast, DSBs near a border produce highly asymmetric DDR platforms, with γH2Ax nearly absent from one broken end. Collectively, our findings lend insights into a basic DNA repair mechanism and how the precise location of a DSB may influence genome integrity.


Changes in plasma lipoproteins and tissue lipoprotein lipase and salt-resistant lipase activities during spawning in the rainbow trout (Salmo gairdnerii R.).
1. Lipoprotein lipase and salt-resistant lipase activities increased in the ovaries but decreased in the adipose tissue of female trout in the months leading up to spawning. 2. The activity of the plasma cholesterol esterifying enzyme increased significantly immediately prior to spawning. 3. Plasma lipoprotein concentrations decreased during the approach to spawning. 4. These studies suggest that the developing ovaries in the trout receive their nutrients by lipolysis of plasma lipoproteins as well as by vitellogenin uptake; differentiation of the roles of the lipid stores in different tissues is proposed.


A practical, robust implementation and sustainability model (PRISM) for integrating research findings into practice.
Although numerous studies address the efficacy and effectiveness of health interventions, less research addresses successfully implementing and sustaining interventions. As long as efficacy and effectiveness trials are considered complete without considering implementation in nonresearch settings, the public health potential of the original investments will not be realized. A barrier to progress is the absence of a practical, robust model to help identify the factors that need to be considered and addressed and how to measure success. A conceptual framework for improving practice is needed to integrate the key features for successful program design, predictors of implementation and diffusion, and appropriate outcome measures. A comprehensive model for translating research into practice was developed using concepts from the areas of quality improvement, chronic care, the diffusion of innovations, and measures of the population-based effectiveness of translation. PRISM--the Practical, Robust Implementation and Sustainability Model--evaluates how the health care program or intervention interacts with the recipients to influence program adoption, implementation, maintenance, reach, and effectiveness. The PRISM model provides a new tool for researchers and health care decision makers that integrates existing concepts relevant to translating research into practice.


Monoclonal antibodies for specific cell labeling: considerations, preparations and preliminary evaluation.
Two types of monoclonal antibodies (MAb), B79.7 and B59.2 determined to be specific for human platelet glycoprotein III.a and III.a.II.b respectively, were labeled with 125I and 111In via diethylenetriaminepentaacetic acid (DTPA) bifunctional chelation technique and evaluated as agents for labeling platelets. Under the chemical conditions chosen one DTPA molecule was bound to one MAb molecule. The specific activities of 111In and 125I preparation averaged 5 and 2.5 Ci/mumol respectively. Both agents showed saturable binding to human platelets. Scatchard analysis showed that the Kd values for 111In-B79.7 and 125I-B79.7 were 83.3 X 10(-9) M and 113.3 X 10(-9) M respectively. The corresponding protein molecules bound per human platelet were 16.75 X 10(3) and 29.5 X 10(3). The Mab B59.2 also reacted with canine platelets and at 50% antigen saturation 49.5% of the added 111In-DTPA-B59.2 was bound to platelets. Using these platelets experimental thrombi were imaged. At 2 h post injection, the thrombi to blood ratios were 15.8. These radiolabeled MAbs are worthy of further evaluation.


Effects of steroids on behavior, electrophysiology, water content and intracranial pressure in cerebral cytotoxic edema.
The effect of therapy with methylprednisolone sodium succinate (5.33 mg/kg/day) and dexamethasone sodium phosphate (1 mg/kg/day) on grey matter of rabbits rendered edematous by a metabolic blocker, 6-aminonicotinamide, is presented. Methylprednisolone was observed to significantly reduce the water content of the grey matter (p less than 0.001), whereas dexamethasone had little effect. Both agents, however, were equally effective in reducing intracranial pressure (p less than 0.001) and improving intracranial elastance, when compared to untreated animals. However, in the dexamethasone-treated group, there was improved behavior and EEG findings in 50% of the animals when compared to the untreated controls, and similar improvement was present in less than 15% of the methylprednisolone group. The disparity between the effects on water content, behavior and EEG supports the thesis that in cerebral edema these agents have a metabolic effect out of proportion to their effect on tissue water.


Perturbation training improves knee kinematics and reduces muscle co-contraction after complete unilateral anterior cruciate ligament rupture.
Dynamic knee stabilization strategies of people who successfully compensate for the absence of an anterior cruciate ligament (ACL) ("copers") are different from those of people who do not compensate well for the injury ("noncopers"). Early after injury, certain patients ("potential copers") can increase the likelihood of successfully compensating for the injury by participating in 10 sessions of perturbation training. The purpose of this study was to determine how perturbation training alters muscle co-contraction and knee kinematics in potential copers. Seventeen individuals with acute, unilateral ACL rupture who were categorized as potential copers and 17 subjects without injuries who were matched by age, sex, and activity level were recruited for this study. Motion analysis and electromyographic data were collected as subjects walked across a stationary or moving platform (horizontal translation) before and after perturbation training. Before training, potential copers had higher co-contraction indexes and lower peak knee flexion angles than subjects without injuries. After training, potential copers' movement patterns more closely resembled those of subjects without injuries (ie, they showed reduced co-contraction indexes and increased peak knee flexion angles during stance). Perturbation training reduced quadriceps femoris-hamstring muscle and quadriceps femoris-gastrocnemius muscle co-contractions and normalized knee kinematics in individuals with ACL rupture who were classified as potential copers. Findings from this study provide evidence for a mechanism by which perturbation training acts as an effective intervention for promoting coordinated muscle activity in a select population of people with ACL rupture.


Acute arterial thrombosis in rabbits: reduced platelet accumulation after treatment with thromboxane synthetase inhibitor dazoxiben hydrochloride, (UK-37, 248-01).
Acute thrombosis was induced in the carotid arteries of anaesthetised rabbits by local electrical stimulation (1mA for 2 min) of the vessel wall. Histological findings confirmed the platelet-rich composition of the thrombus. Platelet accumulation at the stimulus site was quantitated with "'Indium-labelling of autologous platelets. In rabbits injected intravenously with either 2 mg/kg dazoxiben or 10 mg/kg aspirin, accumulation of labelled platelets was considerably reduced. Animals which received vehicle injection only, showed no such reduced thrombus formation. In separate experiments in anaesthetised rabbits, the levels of TxB2 and 6KPGF1 alpha in clotting blood were measured in blood samples taken from animals which had received the above drug treatments. Aspirin markedly reduced the production of both arachidonate metabolites. In contrast, dazoxiben almost totally inhibited TxB2 production but caused a 3.5 fold increase in the levels of 6KPGF1 alpha. These findings demonstrate an anti-thrombotic effect and confirm the mechanistic selectivity of a thromboxane synthetase inhibitor.


Metallic microneedles with interconnected porosity: A scalable platform for biosensing and drug delivery.
Metallic-based microneedles (MNs) offer a robust platform for minimally invasive drug delivery and biosensing applications due to their mechanical strength and proven tissue and drug compatibility. However, current designs suffer from limited functional surface area or challenges in manufacturing scalability. Here, porous 316L stainless steel MN patches are proposed. Fabricated through a scalable manufacturing process, they are suitable for storage and delivery of drugs and rapid absorption of fluids for biosensing. Fabrication of these MNs involves hot embossing a patch of stainless steel-based feedstock, sintering at 1100 °C and subsequent electropolishing. Optimisation of this manufacturing process yields devices that maintain mechanical integrity yet possess high surface area and associated porosity (36%) to maximise loading capacity. Similarly, a small pore size has been targeted (average diameter 2.22 μm, with 90% between 1.56 μm and 2.93 μm) to maximise capillarity and loading efficiency. This porous network has a theoretical wicking rate of 4.7 μl/s and can wick-up 27 ± 5 μl of fluid through capillary action which allows for absorption of pharmaceuticals for delivery. When inserted into a metabolite-loaded skin model, the MNs absorbed and recovered 17 ± 3 μl of the metabolite solution. The drug delivery performance of the porous metallic MNs (22.4 ± 4.9 µg/cm2) was found to be threefold higher than that of topical administration (7.1 ± 4.3 µg/cm2). The porous metallic MN patches have been shown to insert into porcine skin under a 19 N load. These results indicate the potential of design-for-manufacturing porous stainless steel MNs in biosensing and drug delivery applications. STATEMENT OF SIGNIFICANCE: Microneedles are micro-scale sharp protrusions used to bypass the stratum corneum, the skin's outer protective layer, and painlessly access dermal layers suitable for drug delivery and biosensing. Despite a depth of research in the area we have not yet seen large-scale clinical adoption of microneedle devices. Here we describe a device designed to address the potential barriers to adoption seen by other microneedles devices. We have developed a scalable, cost effective process to produce medical grade stainless steel microneedle patches which passively absorb and store drugs or interstitial fluid though a porous network and capillary action. This device, with low manufacturing and regulatory burdens may help the large-scale adoption of microneedles.


Endothelial dysfunction induced by postprandial lipemia is neutralized by addition of proteins to the fatty meal.
Postprandial lipemia is known to reduce endothelium-dependent flow-mediated vasodilation (FMD). Because postprandial lipemia can be acutely mitigated when proteins are added to the fatty meal, we investigated whether this mitigation could neutralize the lipemia-induced endothelial dysfunction. Sixteen healthy students (aged 19-23, eight males and eight females) received three different test meals at intervals of 1 week between successive tests. Each meal contained whipping cream alone or whipping cream together with either caseinate or soy protein. The whipping cream contained 33% fat, and 3 ml (= 1 g fat) was given per kg body weight. The proteins added were either 50 g sodium caseinate or 50 g soy protein. FMD was assessed by two-dimensional ultrasonography of the brachial artery in the fasting state and 1, 2, 3, 4, 5, 6, 7, and 8h after the fatty meal. Blood was withdrawn at the same time-points from the other arm. Triglycerides, free fatty acids, and insulin were determined using routine methods, and both L-arginine and asymmetric dimethylarginine (ADMA) were determined by LC-MS. Postprandial lipemia reduced FMD, the reduction reaching a maximum of 58% after 3 h. This impairment of endothelial function was not observed when either of the test proteins had been added to the fatty meal (p < 0.01 for caseinate and p < 0.001 for soy protein). The effects of the protein addition were decreases in triglycerides and free fatty acids, increased insulin concentrations at all time-points, and an increased arginine/ADMA ratio between 1 and 5h after the meal, particularly in the case of the soy protein. We suggest that the neutralization of the lipemia-induced endothelial dysfunction is caused by direct and indirect effects of the proteins insulinotropy and, secondly, by an increased supply of L-arginine.


Association of specific IgE to staphylococcal superantigens with the phenotype of chronic urticaria.
It has been well established that bacterial superantigens lead to the induction and aggravation of chronic inflammatory skin diseases. We investigated the clinical significance of serum specific immunoglobulin E (lgE) to the staphylococcal superantigens staphylococcal enterotoxin A (SEA), staphylococcal enterotoxin B (SEB), and toxic shock syndrome toxin (TSST)-1 in patients with chronic urticaria (CU), focusing on the differences in these prevalences between aspirin-intolerant CU (AICU) and aspirin-tolerant CU (ATCU) patients. Aspirin sensitivity was confirmed by oral aspirin provocation test. There were 66 patients AICU and 117 patients ATCU in the study. Serum IgE antibodies specific for SEA, SEB, and TSST-1 were measured by the ImmunoCAP test and the patients were compared with 93 normal controls (NC). The prevalences of serum specific IgE to staphylococcal superantigens were significantly higher in CU than in NC patients (IgE to SEA, 13.7% vs. 5.4%; IgE to SEB, 12.0% vs. 4.3%; IgE to TSST-1, 18.0% vs. 6.5%; p<0.05, respectively). The patients with specific IgE to SEA, SEB, and TSST-1 had higher serum total IgE levels and higher rates of atopy. Significant associations were noted between the prevalence of specific IgE to SEA and SEB and the HLA DQB1*0609 and DRB1*1302 alleles in the AICU group. We confirmed that a sub-population of patients with CU possesses serum IgE antibodies to SEA, SEB, and TSST- 1. Particularly, the IgE immune response to TSST-1 is associated with aspirin sensitivity in CU patients.


Trainee doctors' preparedness for clinical work in geriatric psychiatry: A survey on 18 preliminary entrustable professional activities.
Research concerning transitions from one rotation to another during medical specialist training is scarce. This study examined trainee doctors' perceived preparedness for core clinical activities, trainee doctors' preparedness levels, and general perceptions of medical specialist training in geriatric psychiatry. Swiss trainee doctors in geriatric psychiatry were surveyed about their perceived preparedness for 18 preliminary entrustable professional activities (EPAs), curricular support, and general perceptions of their medical specialist training. Closed questions were analysed using descriptive statistics, while open questions were subjected to content analysis. The participants comprised 48 trainee doctors (30.4% response rate) who differed in their educational experience (years of residency and specialism) and clinical subspecialisation goals. Trainee doctors felt adequately prepared for most EPAs but less prepared for some, including electroconvulsive therapy, psychotherapy, and treating older adults in the home environment or residential facilities. Despite the trainee doctors' diversity, they did not differ significantly in perceived preparedness for most EPAs. The most often offered suggestions for improving geriatric psychiatry training were intensified clinical supervision and a structured induction programme. Trainee doctors reported that they felt sufficiently prepared for most EPAs, regardless of their backgrounds and professional goals. However, several professional activities in geriatric psychiatry warrant further training. Our findings indicate the need for a higher intensity of clinical supervision (e.g. more direct observation and specific feedback), the introduction of structured induction programmes (e.g. orientation week), and specific teachings (e.g. on neurocognitive assessment).


Value of dual-energy CT angiography in patients with treated intracranial aneurysms.
To evaluate the ability of dual-energy CT angiography (DECTA) in metal artifact reduction in patients with treated intracranial aneurysms by comparing DECTA-based virtual monoenergetic extrapolations (VMEs) and mixed images (MI). Thirty-five patients underwent prospectively a dual-source DECTA (Somatom Force, Siemens Medical Solutions, Forchheim, Germany) after aneurysm repair. A total number of 40 aneurysms (23 treated by coil embolization and 17 treated by surgical clipping) were analyzed. Mixed images (equivalent to a conventional single-energy CT angiography) were compared to VMEs at 75, 95, and 115 keV. Artifact severity was assessed quantitatively by measuring the mean attenuation value and standard deviation within regions of interest placed in the most hypodense coil or clip artifact area. Artifact severity score and contrast vessel score were also assessed qualitatively by two independent blinded readers. In those aneurysms treated by surgical clipping, quantitative and qualitative analyses showed significant reduction of artifacts on VMEs compared to MI with the best compromise being obtained at 95 keV in order to keep an optimal vessel contrast in the adjacent vessel. In those aneurysms treated by coil embolization, there was no significant reduction of artifacts both on quantitative and qualitative analyses. Dual-source DECTA was helpful in order to reduce clip artifacts on VMEs with the optimal adjacent vessel visualization obtained at 95 keV, whereas this technique was not helpful in aneurysms treated by coiling.


Methotrexate-associated EBV-positive vasculitis in the skin: a report of two cases simulating rheumatoid vasculitis.
Rheumatoid vasculitis (RV) is one of the most serious extra-articular complications of rheumatoid arthritis (RA), generally treated with a high dose of immunosuppressive drugs. Recently, we encountered two cases of ulcerative vasculitis in methotrexate (MTX)-prescribed RA patients, which simulated RV; however, Epstein-Barr virus (EBV)-encoded RNA in situ hybridization on their skin biopsies revealed many EBV-positive lymphocytes (over 50 cells/high-power field) within the vessel walls and perivascular stroma, which led us to the diagnosis of EBV-related vasculitis instead of RV. Subsequently, both ulcers regressed after the discontinuation of MTX and no recurrence was noted during the follow-up period. To prevent unnecessary treatment, EBV-positive vasculitis should be added in the differential diagnosis of lymphocytic vasculitis observed in MTX-administered RA patients.


Actin-based motility of endosomes is linked to the polar tip growth of root hairs.
Plant tip growth has been recognized as an actin-based cellular process requiring targeted exocytosis and compensatory endocytosis to occur at the growth cone. However, the identity of subcellular compartments involved in polarized membrane trafficking pathways remains enigmatic in plants. Here we characterize endosomal compartments in tip-growing root hair cells. We demonstrate their presence at the growing tip and differential distribution upon cessation of tip growth. We also show that both the presence of endosomes as well as their rapid movements within the tip region depends on an intact actin cytoskeleton and involves actin polymerization. In conclusion, actin-propelled endosomal motility is tightly linked to the polar tip growth of root hairs.


Surgical treatment of unstable pelvic fracture in children: long term results.
Paediatric pelvic fractures are rare lesions. In the literature still controversy exists regarding the management of these injuries. The sequelae of these types of lesions has been described. We report the management and long term outcome of 8 patients with paediatric pelvic fractures treated in our institution. Associated injuries to the Risser's growth nuclei are described that has not been previously reported. Anatomical reduction of the displaced fracture should be considered to minimise the risk of long term functional impairment.


Dementia families: Relinquishing home care to aged care services: Guilt, traumatic loss and growth.
Few studies explore both negative and positive perspectives of family members who relinquish home care of a family member with dementia for systemic aged care. This phenomenological study sought the 'lived' experience of relinquishing the role of home carer for a family member with mild to severe dementia to others within care home settings, by seeking to understand the impact of aged care on family members' psychological well-being. Using semi-structured interviews, positive and negative subjective interpretations from 17 families (27 individuals) provided data for analysis, following the protocols of interpretative phenomenological analysis. One superordinate theme, mistrust/integrity, overarched oscillation between mistrust of the aged care system and a struggle for personal integrity in caring for these participants. Two sub-themes emerged: intrinsic trauma and extrinsic trauma. Intrinsic trauma explained feelings of helplessness and guilt, and internally directed responses that triggered a retreat into submission ultimately reducing the participant's role in advocacy. Extrinsic trauma represented externally directed responses such as anger and frustration, where family members became more engaged and watchful and recognised a need for vigilance and advocacy. Paradoxically oscillating between these personal struggles, participants exhibited growth, a third theme that defined assertive/advocacy utilised to nurture hope, gratitude, courage and change. Family members experienced complex distress as they relinquished home care to others within systemic aged care for a member with dementia. By developing adaptive responses as appropriate, for example, advocating for their family member or accepting compliance with treatment, collaborative care between family and staff created better outcomes for the family member with dementia.


Linking self-reported childhood behavioral inhibition to adolescent social phobia.
Behavioral inhibition in children has been hypothesized to be a risk factor for the later development of social phobia. However, this hypothesis has yet to be demonstrated in a prospective study. The purpose of the study presented here is to test whether behavioral inhibition in childhood constitutes a risk factor for social phobia during adolescence. The sample consisted of 2,242 high school students assessed over a 4-year period. Assessments included self-report questionnaires, structured clinical interviews, and measurements of heart rate. Cox proportional hazards models were used to evaluate risk. Social avoidance, a component of behavioral inhibition, predicted onset of social phobia during high school. However, social avoidance was not related to depression in adolescence. Another component of behavioral inhibition, fearfulness, increased the risk for both social phobia and depression. Among subjects who were both socially avoidant and fearful, 22.3% developed social phobia--a risk more than four times greater than that for subjects with neither feature of behavioral inhibition. This prospective study demonstrates that behavioral inhibition in childhood increases the risk of social phobia in adolescence.


The demand for ascorbate recycling capacity rises as the ascorbate pool size increases in Arabidopsis plants.
Ascorbate recycling is required for high ascorbate accumulation. Hence, when the ascorbate pool size is small, does the demand for ascorbate recycling decrease? We herein investigate the impact of ascorbate recycling capacity on ascorbate pool size in an ascorbate-deficient background. Our findings demonstrate that a smaller ascorbate pool size lowers the need for ascorbate recycling capacity even under light stress.


Distinct Immune Gene Programs Associated with Host Tumor Immunity, Neoadjuvant Chemotherapy, and Chemoimmunotherapy in Resectable NSCLC.
Our understanding of the immunopathology of resectable non-small cell lung cancer (NSCLC) is still limited. Here, we explore immune programs that inform of tumor immunity and response to neoadjuvant chemotherapy and chemoimmunotherapy in localized NSCLC. Targeted immune gene sequencing using the HTG Precision Immuno-Oncology panel was performed in localized NSCLCs from three cohorts based on treatment: naïve (n = 190), neoadjuvant chemotherapy (n = 38), and neoadjuvant chemoimmunotherapy (n = 21). Tumor immune microenvironment (TIME) phenotypes were based on the location of CD8+ T cells (inflamed, cold, excluded), tumoral PD-L1 expression (<1% and ≥1%), and tumor-infiltrating lymphocytes (TIL). Immune programs and signatures were statistically analyzed on the basis of tumoral PD-L1 expression, immune phenotypes, and pathologic response and were cross-compared across the three cohorts. PD-L1-positive tumors exhibited increased signature scores for various lymphoid and myeloid cell subsets (P < 0.05). TIME phenotypes exhibited disparate frequencies by stage, PD-L1 expression, and mutational burden. Inflamed and PD-L1+/TILs+ NSCLCs displayed overall significantly heightened levels of immune signatures, with the excluded group representing an intermediate state. A cytotoxic T-cell signature was associated with favorable survival in neoadjuvant chemotherapy-treated NSCLCs (P < 0.05). Pathologic response to chemoimmunotherapy was positively associated with higher expression of genes involved in immune activation, chemotaxis, as well as T and natural killer cells (P < 0.05 for all). Among the three cohorts, chemoimmunotherapy-treated NSCLCs exhibited the highest scores for various immune cell subsets including T effector and B cells (P < 0.05). Our findings highlight immune gene programs that may underlie host tumor immunity and response to neoadjuvant chemotherapy and chemoimmunotherapy in resectable NSCLC.


Effects of estrogen and fimbria/fornix transection on p75NGFR and ChAT expression in the medial septum and diagonal band of Broca.
NGF receptor-expressing cells located in the basal forebrain have recently been shown to contain estrogen (E) receptors (Toran-Allerand and MacLusky. 1989. Soc. Neurosci. Abstr. 15: 954). In the present study, we have examined the effects of E-treatment on p75NGFR and choline acetyltransferase (ChAT) expression by neurons in the medial septum (MS) and the vertical (VDB) and horizontal (HDB) limbs of the diagonal band of Broca using immunocytochemical and in situ hybridization techniques. First, since E-treatment has been shown to affect neuronal survival and to stimulate synaptic reorganization and growth within various regions of the brain, we hypothesized that E-treatment might attenuate the loss of p75NGFR immunoreactivity (IR) which occurs in the MS and VDB following transection of the fimbria/fornix. Contrary to our hypothesis, E-treatment did not attenuate the effects of fimbria/fornix transection. In fact, E-treatment alone produced a significant decrease in the number of p75NGFR-IR cells detected in the MS. Subsequent experiments confirmed that chronic E-treatment produces a down-regulation of both p75NGFR-IR and p75NGFR mRNA in the MS and VDB. In the MS, estrogen appeared to affect a subpopulation of p75NGFR-expressing neurons which were also affected by fimbria/fornix transection since the effects of these two treatments were not additive. In addition, effects of E-treatment on p75NGFR-IR were sex-specific (observed in females but not in males) and were reversible in the MS after 2 weeks, but not after 4 weeks (allowing 2 weeks recovery), of E-treatment. A time-course analysis revealed that effects of E-treatment on p75NGFR-IR were not observed until after 16 days (MS) or 30 days (VDB) of E-treatment and were preceded by a significant and transient increase in ChAT expression in both the MS and VDB. The data are consistent with the possibility that continuous, long-term exposure to gonadal steroids may contribute to a loss of p75NGFR-expressing neurons with age. In addition, the data suggest that p75NGFR expression may play a role in regulating the functioning of specific basal forebrain cholinergic neurons. Different mechanisms by which E-treatment might influence ChAT and p75NGFR expression in brain are discussed.


Changes in unit structures and infanticide observed in Arsi geladas.
In 1989 a new gelada baboon ( Theropithecus gelada) population was found in Arsi, on the opposite side of the Rift Valley to that of the known gelada populations of Semien and Showa. Previous comparisons of units of the band at Gado Goro, Arsi, in the same season in consecutive years, indicated that unit structure is less stable among Arsi geladas as compared to the Semien population. Gelada units of the band at Gado-Goro were studied for 7 months in order to investigate the processes of social changes. Changes in unit structure were observed. Provisioning was carried out for 1.5 months at the beginning of the 7-month study period, in order to capture and obtain blood samples from the geladas. Following this, changes in male leadership of some units were observed, presumably as a consequence of the capture. However, natural changes also occurred. One change in unit structure occurred after a female gave birth, and changes in another unit occurred after the disappearance of the leader male. These changes involved female desertion of a unit, her subsequent transfer to a male unit, and culminated in the formation of a unit consisting of one female and one male. One successful and one attempted case of unification of units, and one case of change of a unit leader male are reported. These changes occurred among eight resident units in a period of 7 months (196 female months). Though the types of social changes were not much different from previous observations in Semien National Park, their frequencies seemed to be much higher. The characteristics of Arsi gelada social changes are proposed to be related to the small size of the units. We also describe a new confirmed case and one suspected case of infanticide, as well as one case of abortion at the time of male leader change.


Molecular analysis of a variant 18;22 translocation in a case of lymphocytic lymphoma.
We previously reported a 5' rearrangement of the BCL2 locus in a t(18;22) variant translocation found in a lymphocytic lymphoma. Primary structure analysis of both rearranged chromosomes confirmed the localization of the breakpoint in the so-called vcr region (for variant cluster region) that encompasses Z-DNA stretches 5' of the BCL2 locus, and in between J lambda 1 and C lambda 1 segments on the IGL locus. A 1,027 nucleotide segment from chromosome 22 was repeated on both derivative chromosomes 18q+ and 22q-. This segment contained an octanucleotide that was also present in the normal chromosome 18 close to the breakpoint. As a consequence of the translocation, a normal-sized BCL2 transcript was overexpressed in tumor cells.


In-situ Raman study on kinetics behaviors of hydrated bubble in thickening.
Natural gas leakage by means of bubbles in cold seep abundantly existed on the ocean floor, causing the change of ocean ecology and the increase of atmospheric temperature. Fortunately, hydrated bubbles as a way of methane sequestration can reduce the effect on the ocean ecology and the escape of gas bubbles from the ocean floor, and are getting attention. To know the growth mode and efficiency of gas hydrate sequestration on bubble, the thickening growth kinetics of hydrated bubble was studied in present work. In-situ Raman spectroscopy was used to analyze the evolution of gas pores and mass transfer channels in the sI CH4, sI CH4-C2H6 and sII CH4-C2H6 hydrate films on the hydrated bubble by the peak area ratio of Raman spectra. Three types of Raman spectra (a-, b-, and c-type), three texture structures of film (Large gas pore; Small gas pore; No gas pore) and two hydrate thickening patterns (filling of new hydrate within large gas pores; covering growth on the original hydrate lattice) were provided in the thickening of hydrated bubble. Results showed that the thickening of the hydrated bubble was a multi-stages growth, i.e., quick growth (stage I), slow growth (stage II), and no growth (stage III). The texture structures and the type and size of gas pore in hydrated bubble were critical for the kinetics growth rate of hydrated bubble in thickening. Especially, the theory of heterogeneous growth of hydrated bubble was proposed to apply the hydrate growth at the interface of two or multi- bubbles, accelerating the efficiency of carbon sequestration as the hydrated bubble. This study will provide a better theoretical basis for understanding the behaviors and efficiency of hydrated carbon sequestration on the surface of bubbles resulting from the gas leakage in the hydrate exploitation or the natural cold seep. SYNOPSIS: Hydrated bubble strongly modulates the emission of a potent greenhouse gas from the deep sea.


Synergistic activity of coriander oil and conventional antibiotics against Acinetobacter baumannii.
In this study we investigated the existence of synergistic antibacterial effect between coriander (Coriandrum sativum L.) essential oil and six different antibacterial drugs (cefoperazone, chloramphenicol, ciprofloxacin, gentamicin, tetracycline and piperacillin). The antibacterial activity of coriander oil was assessed using microdilution susceptibility testing and synergistic interaction by checkerboard assays. The association of coriander essential oil with chloramphenicol, ciprofloxacin, gentamicin and tetracycline against Acinetobacter baumannii showed in vitro effectiveness, which is an indicator of a possible synergistic interaction against two reference strains of A. baumannii (LMG 1025 and LMG 1041) (FIC index from 0.047 to 0.375). However, when tested the involvement between coriander essential oil and piperacillin or cefoperazone, the isobolograms and FIC index showed an additive interaction. The in vitro interaction could improve the antimicrobial effectiveness of ciprofloxacin, gentamicin and tetracycline and may contribute to resensitize A. baumannii to the action of chloramphenicol.


Comparing the Safety Action Feedback and Engagement (SAFE) Loop with an established incident reporting system: Study protocol for a pragmatic cluster randomized controlled trial.
Incident reporting is widely used in hospitals to improve patient safety, but current reporting systems do not function optimally. The utility of incident reports is limited because hospital staff may not know what to report, may fear retaliation, and may doubt whether administrators will review reports and respond effectively. This is a clustered randomized controlled trial of the Safety Action Feedback and Engagement (SAFE) Loop, an intervention designed to transform hospital incident reporting systems into effective tools for improving patient safety. The SAFE Loop has six key attributes: obtaining nurses' input about which safety problems to prioritize on their unit; focusing on learning about selected high-priority events; training nurses to write more informative event reports; prompting nurses to report high-priority events; integrating information about events from multiple sources; and providing feedback to nurses on findings and mitigation plans. The study will focus on medication errors and randomize 20 nursing units at a large academic/community hospital in Los Angeles. Outcomes include: (1) incident reporting practices (rates of high-priority reports, contributing factors described in reports), (2) nurses' attitudes toward incident reporting, and (3) rates of high-priority events. Quantitative analyses will compare changes in outcomes pre- and post-implementation between the intervention and control nursing units, and qualitative analyses will explore nurses' experiences with implementation. If effective, SAFE Loop will have several benefits: increasing nurses' engagement with reporting, producing more informative reports, enabling safety leaders to understand problems, designing system-based solutions more effectively, and lowering rates of high-priority patient safety events.


Spike detection based on a pattern recognition approach using a microcomputer.
A system for the detection of spikes and sharp waves (SSWs) in EEGs of epileptic patients is described. The system uses a pattern recognition technique and it is implemented in a hybrid microcomputer. It performs the on-line simultaneous analysis of 4 EEG channels and thus it is appropriate for long-term EEG recording. The performance of the system was considered satisfactory when compared with that of a panel of electroencephalographers.


Detrimental antidepressant drug-drug interactions: are they clinically relevant?
This paper takes the position that detrimental drug-drug interactions (DDIs) involving antidepressants are clinically relevant. In doing so, it begins with a definition of the terms: drug-drug interaction, detrimental, and clinical relevance. It then discusses the issues of proof and provides an overview of the clinically relevant DDIs involving antidepressants. It also gives examples involving drugs besides antidepressants based on the premise that the underlying principles are applicable regardless of the therapeutic classes of the drugs involved.


The production of english vowels by fluent early and late Italian-English bilinguals.
The primary aim of this study was to determine if fluent early bilinguals who are highly experienced in their second language (L2) can produce L2 vowels in a way that is indistinguishable from native speakers' vowels. The subjects were native speakers of Italian who began learning English when they immigrated to Canada as children or adults ('early' vs. 'late' bilinguals). The early bilinguals were subdivided into groups differing in amount of continued L1 use (early-low vs. early-high). In experiment 1, native English-speaking listeners rated 11 English vowels for goodness. As expected, the late bilinguals' vowels received significantly lower ratings than the early bilinguals' vowels did. Some of the early-high subjects' vowels received lower ratings than vowels spoken by a group of native English (NE) speakers, whereas none of the early-low subjects' vowels differed from the NE subjects' vowels. Most of the observed differences between the NE and early-high groups were for vowels spoken in a nonword condition. The results of experiment 2 suggested that some of these errors were due to the influence of orthography.


Eco-friendly phytofabrication of Ficus Benjamina L. based ZnO-doped g-C3N4 nanocomposites for remarkable photocatalysis and antibacterial applications.
The research reported here emphasizes the phytoextract route synthesized ZnO-doped g-C3N4 (GCN) for its photocatalytic activity, which helps to ensure a sustained & healthy environment. The leaf extract solution of Ficus Benjamina L. was used for the synthesis of ZnO nanoparticles, and GCN was prepared via urea using a thermal polymerization process. The flower extract functions as both stabilizers and capping agents during the process of synthesis of ZnO nanoparticles. The synthesized nanocomposites were then calcined at 400 °C and were further characterized with spectroscopy (UV-Vis), diffracted pattern (XRD), and infrared spectroscopy (FTIR). Further, the photocatalytic activity of auramine orange (AO) and methylene blue (MB) dye from phytoextract route synthesized pure ZnO NPs, GCN-Pure, and composites with varied millimolar concentrations of ZnO nanoparticles with GCN of the constant amount was checked. After the complete analysis, it was observed that the series that was prepared of ZnO-GCN nanocomposites showed notable enhancement in the degradation pattern of the methylene blue dye. Apparently, 1.5 mmol (mM) ZnO-GCN presented greater degradation patterns for Auramine orange and Methylene blue dye as compared to other nanocomposites that were synthesized. The observed increased photocatalytic activity has a conceivable explanation. The antibacterial activity studies of the prepared nanocomposites were also performed against the E. coli strain showing an enhanced zone of inhibition towards it.


Patient Utilization of Premium Intraocular Lenses Before and During the COVID-19 Pandemic.
To compare the choice of intraocular lens (IOL) and sociodemographic characteristics between patients who underwent elective cataract surgery before the COVID-19 pandemic and during the pandemic at the Wilmer Eye Institute. A retrospective chart review of patients who underwent cataract surgery before the COVID-19 pandemic (June 1 to November 30, 2019) and during the pandemic (June 1 to November 30, 2020) was conducted. Sociodemographic information, including age, sex, race, and insurance, and choice of IOL (premium or standard) were analyzed. The association between timing of surgery and choice of IOL was analyzed using multivariable logistic regression. The study included 2,877 patients (3,946 eyes) before COVID-19 and 2,564 patients (3,605 eyes) during COVID-19. However, 9.0% (357/3,946) of surgeries before COVID-19 used premium IOLs compared with 11.1% (399/3,605) during COVID-19 ( P =0.004). There was no difference in the racial characteristics of patients between before and during COVID-19. After adjusting for time of surgery and demographics, the odds of choosing premium IOLs for black patients was 0.32 times the odds for white patients ( P <0.001). There was an increase in private-insured patients but a decrease in Medicare-insured patients during COVID-19. After adjusting for time of surgery and demographics, private-insured patients had higher odds of choosing premium IOLs ( P <0.001), whereas Medicaid-insured patients had lower odds ( P =0.007) when compared with Medicare-insured patients. More patients chose premium IOLs during COVID-19 than before COVID-19, concurrent with change in insurance status. White patients were more likely to choose premium IOLs than black patients, as were private-insured patients compared with Medicare-insured patients.


[Diagnostic image (334). A man with a skin wound under the eye].
A 44-year-old man with a facial skin wound after working with a motor lawn mower had an orbital and ocular penetration by a 2.4 cm metal wire, with endophthalmitis caused by a Klebsiella ozaenae.


Increase in the number of fenestrae in mouse endothelial liver cells by altering the cytoskeleton with cytochalasin B.
Endothelial cells of the hepatic sinusoid isolated from mice livers and maintained in culture display typical fenestrae grouped in sieve plates. Treatment with cytochalasin B led to no significant change in the mean diameter of the fenestrae but to an increase in their number and in the porosity of the cells (percentage of the cellular surface opened by the fenestrae) which attained up to 300% of that of the controls. Scanning electron microscopic observations of Triton-extracted cells revealed that these modifications were related to an alteration of the cytoskeleton. The effect of cytochalasin B could be reversed; 3 hr after removal of the drug, the cells recovered their original aspect with sieve plates scattered over their surface. These observations demonstrate that endothelial fenestrae are inducible structures and that the cytoskeleton seems to be involved in their formation.


Value of antenatal corticosteroid therapy in preterm birth.
This prospective observational study was designed to evaluate the magnitude of the corticosteroid-related reduction in the risk of respiratory distress syndrome (RDS), intraventricular hemorrhage and neonatal death according to different etiologic subgroups of preterm delivery. Of 380 patients delivered before 35 weeks' gestation, 155 received a complete course of dexamethasone or betamethasone to promote fetal lung maturation. In logistic models, the steroid-related reduction of RDS was greater among patients with intact membranes as opposed to patients with premature rupture of membranes (excess risk = 0.31; 95% confidence interval (C.I.) = 0.13-0.73; P = 0.007) and in patients with spontaneous preterm labor as compared with other etiologic groups (excess risk = 0.33; 95% C.I. = 0.11-0.98, P = 0.04). On the other hand, the steroid-related reduction of severe (grade III-IV) intraventricular hemorrhage was more marked in growth retarded as opposed to well-grown fetuses (excess risk = 0.15; 95% C.I. = 0.03-0.96, P = 0.04), and in planned as compared with spontaneous preterm deliveries (excess risk = 0.15; 95% C.I. = 0.03-0.96, P = 0.04). Results show that the greatest benefit from antenatal steroids appears to be in preterm deliveries with intact membranes and in planned preterm deliveries.


Panic disorder and gastrointestinal symptoms: findings from the NIMH Epidemiologic Catchment Area project.
Clinical experience and recent reports suggest that there is a high prevalence of gastrointestinal symptoms in patients with panic disorder and that there is a high prevalence of panic disorder in patients with irritable bowel syndrome, a functional gastrointestinal disorder. To assess gastrointestinal symptoms in a nonpatient, community-based sample, the authors surveyed the prevalence of gastrointestinal symptoms in individuals with panic disorder and other or no psychiatric disorders obtained in a national community survey. Subjects were 13,537 respondents at four sites of the National Institute of Mental Health (NIMH) Epidemiological Catchment Area project. DSM-III diagnoses were determined by using the NIMH Diagnostic Interview Schedule (DIS). Gastrointestinal symptoms were assessed from the somatization disorder section of the DIS. Individuals with panic disorder had a significantly higher rate of endorsing gastrointestinal symptoms, including those typically associated with irritable bowel syndrome, than those with other or no psychiatric diagnosis. Findings suggest a diagnostic overlap between panic disorder and irritable bowel syndrome, with similar demographic and clinical characteristics of patients. Limitations of the study are discussed in terms of medical assessment and self-report inventories. Practical and theoretical implications are discussed.


A Group of Long Non-coding RNAs in Blood Acts as a Specific Biomarker of Alzheimer's Disease.
Long non-coding RNAs (lncRNAs) have been identified to be involved in the pathogenesis of Alzheimer's disease (AD). In this study, we evaluated whether lncRNAs can be used to discriminate AD patients from controls and patients with other dementias, such as vascular, Parkinson's disease, behavioral variant frontotemporal, and dementia with Lewy body. In this study, we used three datasets to measure the blood lncRNA levels. A pilot study (dataset 1, n = 40; controls, 20; AD, 20) was used to screen for differentially expressed lncRNAs. Dataset 2 (n = 174; controls, 86; AD, 88) was used to identify a lncRNA panel for the diagnostic model. Dataset 3 (n = 333; control, 60; AD, 54; vascular dementia, 53; Parkinson's disease dementia, 55; behavioral variant frontotemporal dementia, 56; and dementia with Lewy body, 55) was used to validate the diagnostic model. In dataset 1, 12 upregulated and 15 downregulated lncRNAs were identified. In dataset 2, a panel of seven lncRNAs was found to have the ability to differentiate AD patients from controls. Finally, this panel was applied to dataset 3 to successfully distinguish AD from other dementias. This study proposes a panel of seven lncRNAs as specific and promising biomarker for AD diagnosis.


Growth rates of selected Australian tropical rainforest tree species under controlled conditions.
Controlled environment treatments were applied to assess the effects of temperature on the seedling mortality and growth rates of Toona australis and Flindersia brayleyana, two tropical rainforest tree species from northeast Queensland, Australia. Past workers have assigned these two species to the same ecological niche in terms of their response to canopy disturbance and gap-phase regeneration; however, their geographic ranges are very different. The hypothesis was that the species confined to the warm tropics (F. brayleyana) would have higher seedling mortality and a slower growth rate at lower temperatures than the species that occurs over a wide latitudinal range from the warm tropics to cooler temperate environments (T. australis). Significant differences were found in the growth rates of these two species in the warm (29/22° C) and cool (22/10°C), but not the intermediate (24/16° C), day/night temperature regimes. Their growth rates both decreased with decreasing temperature, but the decrease was significantly less for F. brayleyana which had the faster growth rate and lower seedling mortality in the cool regime. These results led to the rejection of the hypothesis and a test of the assignment of these two species to the same ecological niche. The test involved monitoring their growth to sapling-size in the intermediate temperature regime together with four other co-occurring tropical rainforest tree species belonging to different ecological niches. The growth rates and proportions of above-ground biomass allocated to woody tissue distinguished T. australis and a fast-growing pioneer species from F. brayleyana and three primary forest species. The stem heights and aboveground biomass of T. australis and the pioneer species exceeded the other four species by factors ranging from two to five. It is concluded that T. australis does not belong to the same ecological niche as F. brayleyana, and it is recommended that more research be conducted on the ecotypic temperature responses of the taxon T. australis.


Arf1-dependent PLD1 is localized to oleic acid-induced lipid droplets in NIH3T3 cells.
Phospholipase D (PLD) is known to play a role in vesicle transport through the hydrolysis of phosphatidylcholine (PC) to produce the bioactive lipid, phosphatidic acid. Lipid droplets (LDs) are surrounded by a monolayer of phospholipids, including PC and its lyso derivative, and exhibit a number of signaling proteins. Our recent report suggests that the association of adipose differentiation-related protein (ADRP) to LDs is regulated by an ADP-ribosylation factor 1 (Arf1)-dependent mechanism. In the present study, we found an increase in PLD activity accompanied with LD formation in oleic acid-treated NIH3T3 cells. Brefeldin A, an inhibitor of ARF-GEFs, suppressed both PLD activation and LD formation in oleic acid-treated cells. PLD1, but not PLD2, was found to exist in LDs by immunocytochemical analysis. Furthermore, co-existence of PLD1, Arf1, and ADRP was observed in the LD-enriched subcellular fractions obtained from oleic acid-treated NIH3T3 cells by Western blot analysis. PLD1 activity in the LD-enriched fractions was stimulated by exogenously added Arf1. Although LDs were induced in either PLD1- or PLD2-overexpressing CHO cells by oleic acid treatment, the stimulation of PLD activity was observed only in PLD1-CHO cells. Taken together, the data suggest that the activation of Arf1-dependent PLD1 occurs in LDs and may be involved in their physiological function.


Influence of mobile phase composition on surface diffusion in reversed-phase liquid chromatography.
Influence of column temperature and mobile phase composition (phi) on surface diffusion was studied in reversed-phase liquid chromatography using a C(18)-silica gel column and methanol-water mixtures. The temperature dependence of surface diffusion coefficient (D(s)) was explained by considering that of the molecular diffusivity, suggesting the presence of a kind of correlation between surface and molecular diffusions. The influence of phi on D(s) was accounted for by considering the restriction energy (E(r)) for surface diffusion. Physical meanings of the linear correlation between E(r) and the enthalpy change due to sample retention are discussed in connection with the mechanism of surface diffusion.


Association between particulate matter (PM)2·5 air pollution and clinical antibiotic resistance: a global analysis.
Antibiotic resistance is an increasing global issue, causing millions of deaths worldwide every year. Particulate matter (PM)2·5 has diverse elements of antibiotic resistance that increase its spread after inhalation. However, understanding of the contribution of PM2·5 to global antibiotic resistance is poor. Through univariate and multivariable analysis, we aimed to present the first global estimates of antibiotic resistance and burden of premature deaths attributable to antibiotic resistance resulting from PM2·5 pollution. For this global analysis, data on multiple potential predictors (ie, air pollution, antibiotic use, sanitation services, economics, health expenditure, population, education, climate, year, and region) were collected in 116 countries from 2000 to 2018 to estimate the effect of PM2·5 on antibiotic resistance via univariate and multivariable analysis. Data were obtained from ResistanceMap, European Centre for Disease Prevention and Control Surveillance Atlas (antimicrobial-resistance sources), and PLISA Health Information Platform for the Americas. Future global aggregate antibiotic resistance and premature mortality trends derived from PM2·5 in different scenarios (eg, 50% reduced antibiotic use or PM2·5 controlled to 5 μg/m3) were projected until 2050. The final dataset included more than 11·5 million tested isolates. Raw antibiotic-resistance data included nine pathogens and 43 types of antibiotic agents. Significant correlations between PM2·5 and antibiotic resistance were consistent globally in most antibiotic-resistant bacteria (R2=0·42-0·76, p<0·0001), and correlations have strengthened over time. Antibiotic resistance derived from PM2·5 caused an estimated 0·48 (95% CI 0·34-0·60) million premature deaths and 18·2 (13·4-23·0) million years of life lost in 2018 worldwide, corresponding to an annual welfare loss of US$395 (290-500) billion due to premature deaths. The 5 μg/m3 target of concentration of PM2·5 in the air quality guidelines set by WHO, if reached in 2050, was estimated to reduce antibiotic resistance by 16·8% (95% CI 15·3-18·3) and avoid 23·4% (21·2-25·6) of premature deaths attributable to antibiotic resistance, equivalent to a saving of $640 (580-671) billion. This analysis is the first to describe the association between PM2·5 and clinical antibiotic resistance globally. Results provide new pathways for antibiotic-resistance control from an environmental perspective. National Natural Science Foundation of China, Fundamental Research Funds for the Central Universities, Zhejiang University Global Partnership Fund, and China Postdoctoral Science Foundation.


Correction to: Respiratory support in COPD patients after acute exacerbation with monitoring the quality of support (Rescue2-monitor): an open-label, prospective randomized, controlled, superiority clinical trial comparing hospital- versus home-based acute non-invasive ventilation for patients with hypercapnic chronic obstructive pulmonary disease.
An amendment to this paper has been published and can be accessed via the original article.


Retraction of bioprosthetic heart valve cusps: a cause of wide-open regurgitation in right-sided heart valves.
Most failures of bioprosthetic heart valves in children are due to stenosis secondary to thrombus, calcific deposits, or tissue ingrowth. Valve failures due to regurgitation typically involve cuspal detachment, tears, or perforations. We present four cases of prosthetic valve regurgitation in children caused by cuspal retraction without stenosis and describe the morphologic findings related to the valves at autopsy or explantation. A mononuclear cell and giant cell response to the cusps of the valve was a striking finding in one patient.


Phosphorus recovery from aqueous product of hydrothermal carbonization of cow manure.
The work studies the recovery of nutrients (phosphorus and nitrogen) from the process water of acid-assisted hydrothermal carbonization (HTC) of cow manure. Three organic acids (formic acid, oxalic acid, and citric acid) and sulfuric acid were evaluated as additives in HTC. Using 0.3 M sulfuric acid, more than 99% of phosphorus and 15.6% of nitrogen from manure are extracted and dissolved during HTC at 170 °C with 10 min reaction time in a batch reactor. Nutrients (mainly phosphorus) were recovered through precipitation from process water by raising the ionic strength of the solution by addition of salts of magnesium and ammonia, and by raising the pH to 9.5. Subsequently, phosphorus-rich solids were recovered containing almost all (greater than 95%) of the dissolved phosphorus in the sulfuric and formic acid assisted runs. Morphology and qualitative chemical analysis of the precipitates were determined. It is shown by XRD that the precipitate formed from process water generated by HTC with oxalic acid is crystalline, although the diffraction pattern could not be matched with any expected substance.


Pre- and post-palatoplasty Eustachian tube function in infants with cleft palate.
One past study conducted in 1986 reported Eustachian tube dilation with swallowing during the forced response test (FRT) in a very high percentage (>80%) of cleft palate patients both before and after palatoplasty. The present study was designed to determine the reproducibility of those results. The FRT was used to evaluate Eustachian tube function in a cohort of cleft palate children before and after palatoplasty. Pre-palatoplasty FRT data were available for 25 ears and post-palatoplasty data were available for 31 ears; 14 ears had paired pre-post palatoplasty test data. The results for the FRT tests were compared between the pre- and post-palatoplasty groups for the cross-sectional data and for the paired subset of ears. The 3 passive function measures of the FRT, the opening pressure, closing pressure and passive resistance were not different before and after palatoplasty for either data set. Similarly, 2 of the 3 active function measures, active resistance and dilatory efficiency, were not different pre- and post-palatoplasty, but the percent of ears evidencing tubal dilation for the cross-sectional data was 39% and 62% (p=NS) and for the paired subset was 33% and 83% (p=0.04) at the pre- and post-palatoplasty tests. Palatoplasty had no effect on most measures of the FRT, but may have had a positive effect on the ability to dilate the Eustachian tube during swallowing. The high frequency of ears with tubal dilation before palatoplasty reported in the 1986 study was not reproduced but that frequency after palatoplasty was similar.


Association of visceral fat area with pre-frailty in Japanese community-dwelling older adults: a cross-sectional study.
Screening and intervention in pre-frailty can help prevent or delay frailty among older adults. Being overweight has shown associated with pre-frailty, and overweight is highly prevalent among community-dwelling older adults during COVID-19. However, the impact of visceral fat accumulation remains unclear. This study aimed to explore the association between visceral fat area and pre-frailty in community-dwelling older adults. The participants of this study included community-dwelling older adults from three elderly welfare centers. The frailty phenotype was assessed using the frailty screening index. The body composition was measured using bioelectrical impedance analysis. A total of 214 community-dwelling older adults completed the questionnaire and measurements. After excluding 16 frail participants, 149 (75.3%) were pre-frailty. The mean age of participants was 75.4 ± 5.4 years, and 69.7% (138) of participants were women. There were 54 (27.3%) participants with high visceral fat area. The multivariable model showed that participants with high visceral fat area were at increased risk for pre-frailty (adjusted OR, 3.15; 95% CI, 1.26 - 7.87; P = 0.014), even after adjusted for age, sex, health status, and impact of COVID-19 pandemic. This study suggests that the association between visceral fat accumulation and pre-frailty may help to identify a new target for prevention. Further longitudinal studies are needed to determine their mechanisms in older adults.


Aneurysmal bone cyst: its pathogenesis based on angiographic, immunohistochemical and electron microscopic studies.
Based on angiographic, immunohistochemical as well as electron microscopic findings, authors outline a hypothesis for the etiopathogenesis of aneurysmal bone cysts. No changes were found at the arterial site in 16 studied aneurysmal bone cysts, with no signs of an arteriovenous shunt. In certain cases, however, dilated and tortous efferent veins became visible in the late venous phase. Due to the impedance of venous flow, the intracystic pressure increases and the small veins become dilated causing formation of aneurysmal slits. This is supported by the immunohistochemical finding that S-actin shows concentric arrangement around the aneurysmal cavities. Endothelial lining and basal membrane remnants were detectable in places, though the aneurysmal slits were devoid of continuous endothelial lining and basal membrane. We suggested that the aneurysmal bone cyst corresponds to a hemodynamic disturbance and is due to primary or secondary venous malformation of the bones.


Schistosoma mansoni: differential cell death associated with in vitro culture and treatment with Astiban (Roche).
A simple technique for the maintenance in vitro of mature Schistosoma mansoni is described and critically assessed at the ultrastructural level. Females were cultured for 4--6 days with no apparent ultrastructural change, but after this period changes appeared in the cells of the ovary and vitelline gland. At a later stage (10--12 days) lipid bodies appeared in the parenchyma cells. These changes occurred in worms which were active, paired with males and were egg-laying. Thus the activity, pairing behaviour and egg-laying characteristics are not adequate to reveal the true morphological condition and presumably the physiological and biochemical status of cultured worms. This technique was used to study the effect of Astiban on females and the results were compared with worms treated in vivo. Astiban concentrations greater than 30 microgram/ml killed worms within 7--20 h and acted non-selectively. Astiban at low concentrations (10 microgram/ml) during short-term culture (1--3 h) resulted in a selective action of the drug on maturing vitelline cells. Thus, although the degree of cell damage caused by drug treatment was more severe and occurred earlier than the effects observed in worms cultured in vitro without drugs, both treatments resulted in differential cell death.


Development of single-molecule ubiquitination mediated fluorescence complementation to visualize protein ubiquitination dynamics in dendrites.
The ubiquitination/proteasome system is important for the spatiotemporal control of protein synthesis and degradation at synapses, while dysregulation may underlie autism spectrum disorders (ASDs). However, methods allowing direct visualization of the subcellular localization and temporal dynamics of protein ubiquitination are lacking. Here we report the development of Single-Molecule Ubiquitin Mediated Fluorescence Complementation (SM-UbFC) as a method to visualize and quantify the dynamics of protein ubiquitination in dendrites of live neurons in culture. Using SM-UbFC, we demonstrate that the rate of PSD-95 ubiquitination is elevated in dendrites of FMR1 KO neurons compared with wild-type controls. We further demonstrate the rapid ubiquitination of the fragile X messenger ribonucleoprotein, FMRP, and the AMPA receptor subunit, GluA1, which are known to be key events in the regulation of synaptic protein synthesis and plasticity. SM-UbFC will be useful for future studies on the regulation of synaptic protein homeostasis.


A comparative analysis of carer-employees in Canada over time: a cross-sectional analysis of Canada's General Social Survey, 2012 and 2018.
The aims of the study are to identify trends in the socio-demographic, health, and work profiles of Canadian carer-employees (CEs) over time, as well as the gender difference in the intensity of caring. Cross-sectional data from cycles 26 and 32, collected in 2012 and 2018 respectively, of the Canadian General Social Survey (GSS) were used. Logistic, multinomial logistic, and linear regressions were used to estimate how caregiving is associated with caregivers' health, well-being, and work in both cycles. Regressions from both cycles were then compared with chi-square tests for significant differences over time. The proportion of male CEs grew between 2012 and 2018, and women were no longer more likely to be a CE. The intensity of care for female CEs was significantly increased from 2012 to 2018 as compared with their male counterparts. General health (2018: OR = 0.25[0.11, 0.61] vs. 2012: OR = 0.33[0.15, 0.72]) and life satisfaction ([Formula: see text] = -0.42[0.54, -0.30] vs. [Formula: see text] = -0.22[-0.30, -0.14]) were significantly worsened with respect to the role of CEs from 2012 to 2018. Our study provides the evidence that CEs' health and well-being have worsened over time, especially for female CEs, indicating that the needs of CEs are growing at a faster rate than the supports available. The results are meaningful in informing and justifying the provision of CE supports at work in order to sustain CEs in the workplace, such as the carer-friendly workplace policies.


Dopamine-1-receptor stimulation and mucosal tissue oxygenation in the porcine jejunum.
To evaluate the effects of dopamine-1-receptor stimulation on intestinal mucosal tissue oxygenation. Prospective, experimental, controlled trial. Animal research laboratory. Anesthetized domestic pigs (30 to 45 kg). A small segment of the jejunal mucosa and serosa was exposed by midline laparotomy and antimesenteric incision. Fenoldopam, a selective dopamine-1-receptor agonist, was infused in steps, exponentially increasing from 0.6 to 9.6 micrograms/kg/min via a central venous catheter (n = 8, fenoldopam group), whereas a second group (n = 6, saline group) was only given the solvent. Systemic hemodynamics as well as systemic and jejunal acid base and blood gas variables were measured using an arterial catheter, a thermodilution pulmonary artery catheter, and a jejunal venous catheter. Jejunal mucosal and serosal tissue PO2 were measured by means of Clark-type surface oxygen electrodes. Oxygen saturation and relative concentration of mucosal microvascular hemoglobin were measured by means of tissue reflectance spectrophotometry. In the fenoldopam group, systemic oxygen delivery (12.5 +/- 0.8 mL/kg/min at baseline) increased by 56% (p < .001) above baseline values. Mean arterial pressure remained unchanged. Fenoldopam produced a 51% increase in mucosal PO2 (23.8 +/- 2.8 torr [3.2 +/- 0.4 kPa] at baseline; p < .001) and a 31% increase in mucosal hemoglobin oxygen saturation (55.4 +/- 8.3% at baseline; p < .001), but not change in serosal PO2 (58 +/- 4.8 torr [7.7 +/- 0.6 kPa] at baseline). Fenoldopam improves tissue oxygenation of the porcine jejunum in a dose-related manner. This effect is limited to the inner mucosal layer. Dopamine-1-receptor agonists should be evaluated in patients presenting with signs of intestinal mucosal ischemia.


Prospective screening increases the detection of potentially curable hepatocellular carcinoma: results in 8,900 high-risk patients.
Historically, only 10% of patients with hepatocellular carcinoma (HCC) are diagnosed with early-stage, potentially curable disease. In this study, chronic hepatitis virus-infected patients were prospectively screened to determine: (i) the proportion of patients diagnosed with potentially curable HCC, and (ii) survival following curative therapy. The study included 8900 chronic hepatitis virus-infected patients enrolled in a prospective screening programme, of whom 1335 (15.0%) were infected with hepatitis B virus (HBV), 7120 (80.0%) with hepatitis C virus (HCV), and 445 (5.0%) with both HBV and HCV. Screening was conducted every 6 months and included serum alpha-fetoprotein (AFP) measurement and ultrasonography. Curative treatments included liver transplantation, resection, radiofrequency ablation and/or ethanol injection. Hepatocellular carcinoma was diagnosed in 765 (8.6%) patients. Of 1602 patients with cirrhosis, 758 (47.3%) developed HCC. Curative treatment was possible in 523 (68.4%) of the 765 HCC patients. Two- and 5-year rates of overall survival in the curative treatment group were 65% and 28%, respectively, compared with 10% and 0% in the advanced disease group (P < 0.001). Prospective screening of patients at high risk for the development of HCC increases the proportion of patients diagnosed with potentially curable disease. This may result in an increase in the number of longterm survivors. Screening strategies should focus on patients with chronic HBV or HCV infection who have progressed to cirrhosis because more than 40% of these patients will develop HCC.