Willingness to donate eyes and its associated factors among adults in Gondar town, North West Ethiopia.
In Ethiopia, there is a substantial mismatch between need and supply of corneal transplant. Although corneal transplantation service is affected by various factors, willingness to donate eyes is an essential indicator of its availability, accessibility, and acceptability. Therefore, this study aimed to determine the magnitude of willingness to donate eyes and its associated factors, which help to develop appropriate strategies that can address this undersupply and unmet need. A community-based cross-sectional survey was conducted on 774 adults who were selected using multistage random sampling in Gondar town, North West, Ethiopia. The data were collected through interviews. In this survey, 774 adults with a median age of 30 ± 14.33 years participated. The proportion of willing to donate eyes was 37.6% [95% CI: 34.3%-41.3%]. It was positively associated with the religious belief of Christianity [AOR = 1.73, 95% CI: 1.08-2.75], having awareness about eye donation [AOR = 1.38, 95% CI: 1.01-1.92], educational level of high school [AOR = 2.90, 95% CI: 1.72-4.90], and College/University [AOR = 2.23, 95% CI: 1.28-3.87]. The magnitude of willingness to donate eyes was moderate and positively associated with the higher educational level and awareness. It is, therefore, strategic to plan awareness creation programs to mobilize the community.


[Microphonic potentials in guinea pigs with liver damages].
In guinea pigs we produced certain histological liver damage. By 16 guic results of 16 guinea pigs without liver damage. The microphonic potentials of liverdamage animals was lower about 3.4 dB than potentials of healthy animals. Experimence in animals confirmed the hearingloss of inner ear and also pathological adaption by patients with chronic liver parenchym damage.


The neuropeptide TRH has a minor effect on the enzymatic activity of acetylcholinesterase in vitro.
The neuropeptide thyrotropin-releasing hormone (TRH) elicits a variety of physiological effects of which some are due to cholinergic mechanisms. TRH modulates in vivo the effects of compounds affecting acetylcholinesterase (AChE). In the present study the in vitro effects of TRH on the activity of AChE were explored. TRH has no effect at physiologically relevant concentrations. At unphysiologically high concentrations (>5 mM) a slight inhibition was found. This was noticed also when the enzyme was exposed to the amide-free tripeptide analog p-Glu-His-Pro. We conclude that any cholinergic effect of TRH observed in vivo is unlikely to be due to a direct interaction of the peptide with AChE.


Plasminogen activation by single-chain urokinase in functional isolation. A kinetic study.
The kinetics of the activation of Glu- and Lys-plasminogen by single-chain urokinase (sc urokinase) derived from the transformed human kidney cell line TCL-598 have been studied and compared with two-chain urokinase (tc urokinase). Plasminogen activation was determined by the increase in fluorescence polarization of fluorescein-labeled aprotinin, a high affinity inhibitor of plasmin. This methodology allows plasmin generation by sc urokinase to be measured in functional isolation, with no interfering generation of tc urokinase, sc urokinase was found to activate plasminogen to plasmin with apparent Michaelis-Menten-type kinetics. The Km for Glu-plasminogen activation was 47.7 microM, with a catalytic constant of 2.91 min-1. Lys-plasminogen activation by sc urokinase was characterized by a Km of 11.7 microM and a kcat of 5.60 min-1. The Km values for the activation of Glu- and Lys-plasminogen by tc urokinase were found to be similar to those for activation by sc urokinase (36.8 and 9.0 microM, respectively), but the catalytic constants were higher at 36.0 and 118 min-1, respectively. Therefore, on the basis of the catalytic efficiency kcat/Km, sc urokinase seems to have 16-27-fold lower activity than tc urokinase. This activity of sc urokinase is in contrast to its lack of activity against a low molecular weight peptide substrate (less than 0.2% of the activity of sc urokinase). The activation of sc urokinase to tc urokinase by plasmin was also characterized (Km = 3.0 microM, kcat = 105 min-1). Using these data, it was possible to calculate the theoretical rate of plasminogen activation by sc urokinase in the absence of aprotinin, when tc urokinase is generated by the action of plasmin. The calculated rate was in good agreement with that determined experimentally using the chromogenic substrate D-Val-Leu-Lys-p-nitroanilide. These data demonstrate that sc urokinase has properties which distinguish it from conventional serine protease zymogens. The lack of activity against low molecular weight peptide substrates demonstrates the inaccessibility of the substrate-binding pocket. However, there is a moderate activity against plasminogen, suggesting that plasminogen may be acting as both an effector and a substrate for sc urokinase.


Diaphragm function and lung involvement in systemic lupus erythematosus.
Lung involvement was assessed in 30 consecutive patients with systemic lupus erythematosus (SLE), not selected by respiratory symptoms. Pulmonary function tests revealed a higher rate of abnormality than either clinical history or radiography. The single breath carbon monoxide diffusing capacity was below 80 per cent of the predicted value in 24 patients (80 per cent), and a reduced total lung capacity was present in 13 (43 per cent). There was a weak correlation between the severity of the functional defect and disease activity, assessed antinuclear factor and DNA binding. No correlation was found with serum complement of Clq precipitation. Since pulmonary fibrosis in SLE is uncommon it cannot account for the high frequency of abnormal findings, and the pathogenesis of the functional changes is probably multifactorial. In seven of the patients with the smallest lung volumes, measurements of static pressure volume curves and of maximum respiratory pressures indicated extrapulmonary volume restriction. In five of these patients, diaphragm function was specifically assessed and found to be grossly abnormal in four. The inability of the diaphragm to generate normal pressure may be due to either severe weakness or immobility following extensive pleural adhesions. The well recognized syndrome of "shrinking lungs" and high "sluggish" diaphragms with clear lung fields on radiography is probably due to dysfunction of the diaphragm rather than to primary intrapulmonary pathology.


Transcranial sonography of brainstem structures in panic disorder.
Panic disorder has been associated with altered serotonin metabolism in the brainstem raphe. The aim of study was to evaluate the BR echogenicity on transcranial sonography (TCS) in panic disorder. A total of 96 healthy volunteers were enrolled in the "derivation" cohort, and 26 healthy volunteers and 26 panic disorder patients were enrolled in the "validation" cohort. TCS echogenicity of brainstem raphe and substantia nigra was assessed on anonymized images visually and by means of digitized image analysis. Significantly reduced brainstem raphe echogenicity was detected more frequently in panic disorder patients than in controls using both visual (68% vs. 31%) and digitized image analysis (52% vs. 12%). The optimal cut-off value of digitized brainstem raphe echogenicity indicated the diagnosis of panic disorder with a sensitivity of 64% and a specificity of 73%, and corresponded to the 30th percentile in the derivation cohort. Reduced brainstem raphe echogenicity was associated with shorter treatment duration, and, by trend, lower severity of anxiety. No relationship was found between echogenicity of brainstem raphe or substantia nigra and age, gender, severity of panic disorder, or severity of depression. Patients with panic disorder exhibit changes of brainstem raphe on TCS suggesting an alteration of the central serotonergic system.


Cavernous sinus syndrome from self-inflicted gunshot wound: case report and neuroanatomical correlation.
A case of total ophthalmoplegia is presented secondary to attempted suicide by firearm. The case demonstrates classic intermediate cavernous sinus syndrome signs. The neuroanatomy of the region, along with common parasellar syndromes, is reviewed.


Increase in DNA methylation downregulates conceptus interferon-tau gene expression.
Expression of ovine interferon-tau (oIFNtau) genes, essential for the maternal recognition of pregnancy in ruminant ungulates, is restricted to the trophoblast and is not detected in any other cell types or tissues. Substantial secretion of oIFNtau starts on day 12-13 of pregnancy (day 0 = day of estrus), reaches the highest on day 16-17, and then declines rapidly. Ovine IFNtau mRNA, on the other hand, reaches the highest level on day 14 of pregnancy, 2-3 days before peak production of the protein. In this study, day 14 and 17 conceptuses treated with 5-aza-2'-deoxycytidine, an inhibitor of DNA methylation, were cultured in vitro and only day 17, not day 14, conceptuses resulted in upregulation of oIFNtau gene expression. To gain insight into the molecular mechanism of oIFNtau gene downregulation, the methylation status within 1 kb of the 5'-flanking region of oIFNtau-o10 gene was investigated: CpG dinucleotides of this gene in day 14 ovine conceptuses were hypomethylated compared to day 20 conceptuses or other tissues. In vitro methylation of oIFNtau-o10-reporter constructs caused suppression of reporter activity in transient transfections. Cotransfection of methyl-CpG-binding protein (MeCP2) with the reporter construct elicited further suppression of the reporter activity. In electrophoretic mobility shift assay (EMSA), patterns of shifted bands did not show much difference between methylated and unmethylated probes in distal regions, but exhibited differences in the proximal region of upstream sequences of the oIFNtau gene. These results provide evidence that changes in the degree of DNA methylation could be one of the major mechanisms leading to downregulation of the oIFNtau-o10 gene during early gestation, and possibly its silencing in nonconceptus tissues.


An immunogold cell labelling method for rat T lymphocytes.
A method using monoclonal antibodies in conjunction with an immunogold procedure was adapted for labelling T lymphocytes in blood samples obtained from male Wistar rats. The monoclonal antibodies W3/25, MRC/OX8 and W3/13 were used. Changes in the percentages of positively labelled cells were observed in rats dosed with the immunosuppressant cyclosporin.


Absorption of different amino acids by an intestinal preparation from normal rats and from rats exposed to supralethal X-irradiation.
Absorption of different amino acids [lysine, alpha-amino isobutyrate (AIB), methionine, alanine, glycine] was studied in an intestinal in vivo preparation from normal and X-irradiated rats (1 and 3 days after 2000 R). Absorption of amino acids under loading and in presence of other amino acids was also followed. Lysine and AIB absorption follow a saturation kinetics with a maximal velocity of 35 and 85.6 micronmoles/min and a Kt of 10 and 67 micronmoles for lysine and AIB respectively. Interference in absorption exists not only between amino acids of the same class, but also by lysine on neutral amino acids. One day after irradiation, absorption is normal or even enhanced, although active transport appears impaired as indicated by the increase in Kt. Three days after exposure absorption, particularly the active one, is severely depressed. This is indicated by the low Vm and high Kt as well as by the fact that loading has little influence on absorption.


The Significance of Systemic Inflammation Markers in Intrahepatic Recurrence of Early-Stage Hepatocellular Carcinoma after Curative Treatment.
Systemic inflammatory markers (SIMs) are known to be associated with carcinogenesis and prognosis of hepatocellular carcinoma (HCC). We evaluated the significance of SIMs in intrahepatic recurrence (IHR) of early-stage HCC after curative treatment. This study was performed using prospectively collected registry data of newly diagnosed, previously untreated HCC between 2005 and 2017 at a single institution. Inclusion criteria were patients with Barcelona Clinic Liver Cancer stage 0 or A, who underwent curative treatment. Pre-treatment and post-treatment values of platelet, neutrophil, lymphocyte, monocyte, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and lymphocyte/monocyte ratio (LMR) were analyzed with previously well-known risk factors of HCC to identify factors associated with IHR-free survival (IHRFS), early IHR, and late IHR. Of 4076 patients, 2142 patients (52.6%) experienced IHR, with early IHR in 1018 patients (25.0%) and late IHR in 1124 patients (27.6%). Pre-treatment platelet count and PLR and post-treatment worsening of NLR, PLR, and LMR were independently associated with IHRFS. Pre-treatment platelet count and post-treatment worsening of NLR, PLR, and LMR were significantly related to both early and late IHR. Pre-treatment values and post-treatment changes in SIMs were significant factors of IHR in early-stage HCC, independent of previously well-known risk factors of HCC.


Successful aortic surgery after renal transplantation without protection of the transplanted kidney.
When renal transplant recipients undergo aortic surgery, blood supply to the renal graft is interrupted while the aorta is clamped. Several innovative ways of using shunts have been described to preserve blood flow to the transplanted kidney during such surgery on the assumption that temporary warm ischemia of the renal transplant is poorly tolerated. We have performed aortic surgery in four renal transplant recipients without the use of any form of graft protection. One patient underwent urgent operation to treat an expanding aortic aneurysm and the other three had elective surgery for aortoiliac occlusive disease. Ischemic times ranged from 30 to 45 minutes. Two of the four patients had a temporary rise in serum creatinine levels. No patient required hemodialysis. We conclude that in selected renal transplant recipients, aortic surgery can be safely undertaken without graft protection.


Changes in surface hardness of conventional restorative glass ionomer cements.
The effect of a contact with an aqueous solution on the surface hardness of glass ionomers has been investigated in a few studies and for a limited number of formulations. As there is no information on the long-term changes of the surface hardness in this respect, the aim of this study was to determine these long-term changes in 10 conventionally setting glass ionomer formulations after storage in water as compared to maturation in a humid atmosphere (85% RH). After setting for 15 min different series of glass ionomer specimens were stored at 37 degrees C in both experimental media for 1, 7, 28 and 140 days. At the end of the specific maturation times, the mean surface hardness was determined on the basis of Knoop Hardness (KHN). Data were analyzed using ANOVA. In a humid atmosphere the surface hardness generally increases rapidly initially, followed after 1 day by a more gradual increase. In contact with water, the hardness also increases up to one day but not to the same extent. The surface hardness then remains constant or slightly decreases. Evidence of a detrimental softening of the surface ascribed previously to the loss of matrix forming ions was not found. A surface erosion is not likely to occur.


Periodontal Diseases and Traumatic Dental Injuries in the Pediatric Population.
This article provides an overview of periodontal diseases and traumatic dental injuries (TDIs) in children and adolescents, which are serious public health problems worldwide. Periodontal diseases, including gingivitis and periodontitis, commonly affect the oral soft tissues and teeth and often co-occur with other chronic diseases. TDIs are prevalent from an early age and carry high treatment costs. Behavioral and environmental factors contribute to both TDIs and periodontal diseases, but their etiology varies according to population characteristics and case definition. Both conditions may lead to pain, function impairment, esthetic problems, and psychosocial effects, with major consequences on quality of life.


Patterns of change and stability in caregiver burden and life satisfaction from 1 to 2 years after severe traumatic brain injury: A Norwegian longitudinal study.
To assess burden and life satisfaction in family members of patients with severe traumatic brain injury (sTBI) at 1 and 2 years post-injury, examine if change in burden can be predicted by family member and patient demographics, patient's functional status, family members social network or level of burden at 1 year. Prospective national multicenter study. Self-report from family members, patient data collected from a national cohort study on patients with sTBI. 80 family members participated. The Caregiver Burden Scale (CBS), life satisfaction. Total burden increased between years 1 and 2 post-injury (P = 0.04). Thirty percent of the family members reported an increased burden, 55% were stable, and 15% had a decrease in burden between the two follow-up times. Logistic regression analyses revealed that experiencing loneliness was an independent predictor of increased burden from 1 to 2 years post-injury (OR = 4.35, P < 0.05). Life Satisfaction was lower at the 2 year follow-up than at 1 year (p = 0.03). The results demonstrate a need for long-term follow-up of patients and family members that focuses on professional support to relieve burden and risk of loneliness or social isolation. This group may benefit from additional follow-up interventions tailored to their needs.


Myogenesis and contraction in the early embryonic heart of the rainbow trout. An electron microscopic study.
Myogenesis in the embryonic heart of the rainbow trout, Salmo gairdneri (Rich.), was investigated electron microscopically from the 29th to the 41st somite stage. Thick and thin myofilaments are formed simultaneously as well as precursors of Z-lines, to which the thin filaments are attached. The genesis of filaments takes place in the region around the intracellular yolk droplets. The first myofibrils appear by the 33rd somite stage, probably formed by a mechanism of self-assembly in which the binding sites of actin and myosin participate. A- and I-bands do not develop before the 38th osmite stage. The contraction already begins during the 33rd somite stage in the middle of the tubular heart. Gradually, the peristaltic waves spread increasingly to other parts of the heart. In the 41st somite stage the entire heart is contractile and all myocytes contain myofibrils.


Gender stereotyping in medical interaction: A Membership Categorization Analysis.
Gender can be a valuable resource in communication but also a problem, perpetuating gender stereotypes. So far, there has been little attention for how healthcare professionals and patients make gender relevant in medical interactions. The approach of Membership Categorization Analysis (MCA) is particularly pertinent to meticulously analyze gender in medical communication. Applying MCA, this study analyzes how activity descriptions implicitly associated with gender stereotypes, e.g., "carrying a laundry basket up the stairs", feature in the course of GPs' explanations of a question or diagnosis. The aim is to provide a new perspective on the relationship between gender and medical interaction, and to increase our understanding of how gender stereotypes are reproduced in the medical setting. Two cases of GPs using gendered explanations in Dutch general practice interactions are analyzed turn-by-turn using MCA. The findings show how GPs' descriptions of gendered activities serve the exemplification of technical terms, designed for the specific patient, while also casting the patient in a traditional gender role. Invoking gender in medical interaction may serve a communicative goal while also perpetuating stereotypes. Insight in the subtleties of gender construction in medical interactions could enhance gender awareness and sensitivity in healthcare.


Evaluation of Gelatin Microparticles as Adherent-Substrates for Mesenchymal Stem Cells in a Hydrogel Composite.
Due to the lack of cell-adhesive moieties in traditional synthetic hydrogels, the present work investigated the use of degradable gelatin microparticles (GMPs) as temporary adherent substrates for anchorage-dependent mesenchymal stem cells (MSCs). MSCs were seeded onto GMPs of varying crosslinking densities and sizes to investigate their role on influencing MSC differentiation and aggregation. The MSC-seeded GMPs were then encapsulated in poly(ethylene glycol)-based hydrogels and cultured in serum-free, growth factor-free osteochondral medium. Non-seeded MSCs co-encapsulated with GMPs in the hydrogels were used as a control for comparison. Over the course of 35 days, MSCs seeded on GMPs exhibited more cell-cell contacts, greater chondrogenic potential, and a down-regulation of osteogenic markers compared to the controls. Although the factors of GMP crosslinking and size had nominal influence on MSC differentiation and aggregation, GMPs demonstrate potential as an adherent-substrate for improving cell delivery from hydrogel scaffolds by facilitating cell-cell contacts and improving MSC differentiation.


Acute supraglottitis in adults: what's the optimal airway intervention?
To validate the Friedman stage and define the proper timing for airway intervention in adult cases of acute supraglottitis, we evaluated the clinical courses and management of adult patients. 202 adult patients with acute supraglottitis were included in this study. The diagnosis of supraglottitis was established by flexible nasolaryngoscopic examination. Friedman stages were classified in each patient. In this study, the first three days of serial nasolaryngoscopic findings for each patient were evaluated. All patients were treated successfully with only conservative methods. There were no significant differences between patients with Friedman stages I or II/III. Among the patients that had serial nasolaryngoscopic findings, only one patient presented with progressive swelling of the epiglottis, and there were no cases of persistent swelling. The airway intervention threshold should be raised from Friedman stages II-III. And, airway intervention should not be needed if patients are tolerant of their respiratory discomfort.


ATM function and telomere stability.
Accumulation of DNA damage has been associated with the onset of senescence and predisposition to cancer. The gene responsible for ataxia telangiectasia (A-T) is ATM (ataxia-telangiectasia mutant), a master controller of cellular pathways and networks, orchestrating the responses to a specific type of DNA damage: the double strand break. Based on the homology of the human ATM gene to the TEL1, MEC1 and rad3 genes of yeast, it has now been demonstrated that mutations in ATM lead to defective telomere maintenance in mammalian cells. While ATM has both nuclear and cytoplasmic functions, this review will focus on its roles in telomere metabolism and how ATM and telomeres serve as controllers of cellular responses to DNA damage.


Prospective comparison of double contrast barium enema plus flexible sigmoidoscopy v colonoscopy in rectal bleeding: barium enema v colonoscopy in rectal bleeding.
Rectal bleeding often heralds serious colonic disease. The literature suggests that colonoscopy is superior to barium enema plus sigmoidoscopy, although no good comparative studies exist. Seventy one patients with overt rectal bleeding had prospectively flexible sigmoidoscopy, double contrast barium enema and colonoscopy completed independently. Against the gold standard, the sensitivity and specificity of colonoscopy were 0.69 and 0.78 respectively for a spectrum of colonic lesions, while for combined flexible sigmoidoscopy and double contrast barium enema these values were 0.80 and 0.56, respectively. When assessing adenoma or carcinoma, colonoscopy was more sensitive at 0.82 v 0.73, while flexible sigmoidoscopy plus double contrast barium enema was superior for detecting diverticular disease. The positive predictive value for colonoscopy was 0.87 against 0.81 for flexible sigmoidoscopy and double contrast barium enema. This study confirms that colonoscopy should be a first line investigation in subjects likely to require biopsy or therapeutic intervention.


The stability of markers in dried-blood spots for recommended newborn screening disorders in the United States.
We aimed to measure separately the contributions of heat and humidity to changes in levels of 34 markers of inborn disorders in dried-blood-spot (DBS) samples. We stored paired sets of DBSs at 37°C for predetermined intervals in low-humidity and high-humidity environments. Marker levels of all samples in each complete sample set were measured in a single analytic run. During the 30 ± 5 day studies, galactose-1-phosphate uridyltransferase and biotinidase lost almost 65% of initial activities in low-humidity storage; most of the degradation in 27 other markers was attributable to adverse effects of high-humidity storage; seven markers in DBSs stored at high humidity lost more than 90% of initial levels by the end of the study and 4 of the 7 lost more than 50% of initial levels within the first week of storage. Minimizing both humidity and temperature in DBS transportation and storage environments is essential to maintaining sample integrity.


Candida tropicalis induces NLRP3 inflammasome activation via glycogen metabolism-dependent glycolysis and JAK-STAT1 signaling pathway in myeloid-derived suppressor cells to promote colorectal carcinogenesis.
Our previous studies showed that Candida tropicalis promoted colorectal cancer (CRC) by activating the function of MDSCs. However, underlying molecular mechanisms remains to be further investigated. In the present study, we indicated that C. tropicalis induced NLRP3 inflammasome activation through Dectin-3 in myeloid-derived suppressor cells (MDSCs). Mechanistically, we identified that C. tropicalis significantly enhanced the levels of glycolysis dependent on glycogen metabolism in MDSCs, which was required for NLRP3 inflammasome activation. C. tropicalis-induced NLRP3 inflammasome activation of MDSCs required the first priming signal and the second activation signal. For one thing, C. tropicalis promoted transcription of Nlrp3, Pro-caspase-1 and IL-1β genes through activation of JAK-STAT1 signaling pathway. For another, mtROS as the second activation signal mediated C. tropicalis-induced activation of NLRP3 inflammasome. Pharmacological inhibition of NLRP3 inflammasome activation abolished the pro-tumorigenic effect of C. tropicalis in an AOM/DSS-induced CAC mice model and significantly reduced C. tropicalis-promoted infiltration of MDSCs in colon tumors. Finally, in human CRC samples, the expression of STAT1, p-STAT1 and NLRP3 was elevated in MDSCs infiltrated by CRC. Collectively, these findings shed light on a previously unidentified mechanism by which C. tropicalis induces NLRP3 inflammasome activation in MDSCs to contribute to the progression of CRC. And STAT1-NLRP3 axis might represent a prospective therapeutic target for the treatment of CRC.


Contrast-Enhanced Mammography Implementation, Performance, and Use for Supplemental Breast Cancer Screening.
Contrast-enhanced mammography (CEM) is an emerging breast imaging technology that provides recombined contrast-enhanced images of the breast in addition to low-energy images analogous to a 2-dimensional full-field digital mammogram. Because most breast imaging centers do not use CEM at this time, a detailed overview of CEM implementation and performance is presented. Thereafter, the potential use of CEM for supplemental screening is discussed in detail, given the importance of this topic for the future of the CEM community. Diagnostic performance, safety, and cost considerations of CEM for dense breast tissue supplemental screening are discussed.


Bioinformatic Analysis of B- and T-cell Epitopes from SARS-CoV-2 Structural Proteins and their Potential Cross-reactivity with Emerging Variants and other Human Coronaviruses.
The mutations in SARS-CoV-2 variants of concern (VOC) facilitate the virus' escape from the neutralizing antibodies induced by vaccines. However, the protection from hospitalization and death is not significantly diminished. Both vaccine boosters and infection improve immune responses and provide protection, suggesting that conserved and/or cross-reactive epitopes could be involved. While several important T- and B-cell epitopes have been identified, mainly in the S protein, the M and N proteins and their potential cross-reactive epitopes with other coronaviruses remain largely unexplored. To identify and map new potential B- and T-cell epitopes within the SARS-CoV-2 S, M and N proteins, as well as cross-reactive epitopes with human coronaviruses. Different bioinformatics tools were used to: i) Identify new and compile previously-reported B-and T-cell epitopes from SARS-CoV-2 S, M and N proteins; ii) Determine the mutations in S protein from VOC that affect B- and T-cell epitopes, and; iii) Identify cross-reactive epitopes with coronaviruses relevant to human health. New, potential B- and T-cell epitopes from S, M and N proteins as well as cross-reactive epitopes with other coronaviruses were found and mapped within the proteins' structures. Numerous potential B- and T-cell epitopes were found in S, M and N proteins, some of which are conserved between coronaviruses. VOCs present mutations within important epitopes in the S protein; however, a significant number of other epitopes remain unchanged. The epitopes identified here may contribute to augmenting the protective response to SARS-CoV-2 and its variants induced by infection and/or vaccination, and may also be used for the rational design of novel broad-spectrum coronavirus vaccines.


Growth hormone prevents Fas-induced apoptosis in lymphocytes through modulation of Bcl-2 and caspase-3.
Growth hormone (GH) has been reported to have a potent effect on the immune system. However, the detailed mechanism of the effect of GH on the immune system has not yet been clarified. This study was designed to investigate the nature of this mechanism. In the present study, we investigated the effects of GH on the susceptibility of both human CEM/C7 lymphocytes and human IM-9 lymphocytes to Fas-induced apoptosis. Both cell lines expressed GH receptor mRNA. GH rescued Fas-induced suppression of [(3)H]-thymidine incorporation into each cell line. GH prevented Fas-induced apoptosis in each cell line without changing Fas antigen expression. We next investigated the mechanisms of the prevention of Fas-induced apoptosis, by focusing on intracellular molecules related to the apoptotic signal. Bcl-2 expression was increased by GH treatment in both CEM/C7 and IM-9 lymphocytes. GH also downregulated caspase-3 expression and inhibited activation of caspase-3 in both cell lines. These findings suggest that GH regulates the human immune system through inhibition of Fas-induced apoptosis in activated T and B lymphocytes.


Laparoendoscopic single site (LESS) surgery in benign gynecology: perioperative and late complications of 515 cases.
To present 515 LESS surgeries and report the perioperative outcomes and late complications according to the Clavien-Dindo classification. We performed a prospective single-center study (Canadian Task Force classification II-2). One surgeon trained in minimally invasive surgery performed 515 cases of LESS surgery from May 2008 to September 2011. LESS gynecological surgery was performed on 515 patients (274 total hysterectomies; 26 subtotal hysterectomies; 87 adnexectomies including oophorectomy, salpingectomy, and salpingo-oophorectomy; 100 ovarian cystectomies; 17 myomectomies; 11 others). The median age and body mass index of the patients were 45 years and 22.6 kg/m², respectively. LESS surgery was successfully completed in 493 patients (95.7%) without the need for one or more ancillary ports or conversion to laparotomy. Twenty patients needed one or more additional ports and two cases were converted to laparotomy. One or more additional ports were required most frequently in ovarian cystectomy procedures (12/100, 12%). Thirty-six patients (7.0%) required intraoperative and/or postoperative transfusions. Each of these patients underwent hysterectomy (33/274, 12.0%) or subtotal hysterectomy (3/26, 11.5%). Perioperative complications (<30 postoperative days), excluding transfusions, occurred in 8 patients (1.6%) and included one case each of vault bleeding, vault abscess, stump watery discharge, rectal injury, and vesicovaginal fistula, and three cases of urinary tract injury. Late complications occurred in three patients (0.6%) and included two umbilical hernias and one vault evisceration. The overall complication rate, excluding transfusions, was 2.1% (11/515). The rate of late postoperative complications, including umbilical port site hernia and vault evisceration, was not increased in this study, as compared to previous reports of single-port and conventional laparoscopic surgeries.


Egg n-3 fatty acid composition modulates biomarkers of choline metabolism in free-living lacto-ovo-vegetarian women of reproductive age.
The lacto-ovo-vegetarian (LOV) dietary regimen allows eggs, which are a rich source of choline. Consumption of eggs by LOV women may be especially important during pregnancy and lactation when demand for choline is high. The aim of this single blind, randomized, crossover-feeding study was to determine how near-daily egg consumption influenced biomarkers of choline metabolism in healthy LOV women of reproductive age (n=15). Because long-chain n-3 fatty acids could influence choline metabolism, the effect of n-3-enriched vs nonenriched eggs on choline metabolites was also investigated. Three 8-week dietary treatments consisting of six n-3-enriched eggs per week, six nonenriched eggs per week, and an egg-free control phase were separated by 4-week washout periods. Choline metabolites were quantified in fasted plasma collected before and after each treatment and differences in posttreatment choline metabolite concentrations were determined with linear mixed models. The n-3-enriched and nonenriched egg treatments produced different choline metabolite profiles compared with the egg-free control; however, response to the eggs did not differ (P>0.1). Consumption of the n-3-enriched egg treatment yielded higher plasma free choline (P=0.02) and betaine (P<0.01) (vs egg-free control) concentrations, whereas consumption of the nonenriched egg treatment yielded borderline higher (P=0.06) plasma phosphatidylcholine (vs egg-free control) levels. Neither egg treatment increased levels of plasma trimethylamine oxide, a gut-flora-dependent oxidative choline metabolite implicated as a possible risk factor for cardiovascular disease. Overall these data suggest that egg fatty-acid composition modulates the metabolic use of choline.


Collision Cross Section Calculations Using HPCCS.
A technical overview of the High Performance Collision Cross Section (HPCCS) software for accurate and efficient calculations of collision cross sections for molecular ions ranging from small organic molecules to large protein complexes is presented. The program uses helium or nitrogen as buffer gas with considerable gains in computer time compared to publicly available codes under the Trajectory Method approximation. HPCCS is freely available under the Academic Use License at https://github.com/cepid-cces/hpccs .


Knockdown of splicing factor SRp20 causes apoptosis in ovarian cancer cells and its expression is associated with malignancy of epithelial ovarian cancer.
Our previous study revealed that two splicing factors, polypyrimidine tract-binding protein (PTB) and SRp20, were upregulated in epithelial ovarian cancer (EOC) and knockdown of PTB expression inhibited ovarian tumor cell growth and transformation properties. In this report, we show that knockdown of SRp20 expression in ovarian cancer cells also causes substantial inhibition of tumor cell growth and colony formation in soft agar and the extent of such inhibition appeared to correlate with the extent of suppression of SRp20. Massive knockdown of SRp20 expression triggered remarkable apoptosis in these cells. These results suggest that overexpression of SRp20 is required for ovarian tumor cell growth and survival. Immunohistochemical staining for PTB and SRp20 of two specialized tissue microarrays, one containing benign ovarian tumors, borderline/low malignant potential (LMP) ovarian tumors as well as invasive EOC and the other containing invasive EOC ranging from stage I to stage IV disease, reveals that PTB and SRp20 are both expressed differentially between benign tumors and invasive EOC, and between borderline/LMP tumors and invasive EOC. There were more all-negative or mixed staining cases (at least two evaluable section cores per case) in benign tumors than in invasive EOC, whereas there were more all-positive staining cases in invasive EOC than in the other two disease classifications. Among invasive EOC, the majority of cases were stained all positive for both PTB and SRp20, and there were no significant differences in average staining or frequency of positive cancer cells between any of the tumor stages. Therefore, the expression of PTB and SRp20 is associated with malignancy of ovarian tumors but not with stage of invasive EOC.


Absence of aluminium compromises root integrity, reduces leaf hydration and Rubisco performance in Qualea grandiflora, an Al-accumulating species.
Aluminium (Al) is toxic to most plants. Nevertheless, some species accumulate Al without showing toxicity symptoms. Previous studies have evidenced Al in chloroplasts of Al-accumulating species from the Cerrado vegetation in South America. We ask whether Al increases carbon assimilation through enhanced apparent efficiency of Rubisco. Seedlings of the Al-accumulator Qualea grandiflora (Vochysiaceae) were grown in nutrient solution with 0, 740, and 1480 μm Al. Growth parameters, relative leaf water content, Al concentration in organs, gas exchange and apparent carboxylation efficiency (measured from A/Ci curves) were evaluated for 60 days. Plants without Al showed no root growth, necrotic roots, low gas exchange rates, and decreased apparent carboxylation efficiency. Al-treated plants, however, showed new white roots and increased root biomass leading to higher leaf hydration, and apparent carboxylation efficiency was higher in these plants. Increased Al available in the nutrient solution increased Al accumulation in plant organs. Absence of Al compromised root integrity in Q. grandiflora, thus limiting leaf hydration. No positive direct effect of Al on Rubisco was evidenced in Al-treated plants.


A review of ultrasonic sensing and machine learning methods to monitor industrial processes.
Supervised machine learning techniques are increasingly being combined with ultrasonic sensor measurements owing to their strong performance. These techniques also offer advantages over calibration procedures of more complex fitting, improved generalisation, reduced development time, ability for continuous retraining, and the correlation of sensor data to important process information. However, their implementation requires expertise to extract and select appropriate features from the sensor measurements as model inputs, select the type of machine learning algorithm to use, and find a suitable set of model hyperparameters. The aim of this article is to facilitate implementation of machine learning techniques in combination with ultrasonic measurements for in-line and on-line monitoring of industrial processes and other similar applications. The article first reviews the use of ultrasonic sensors for monitoring processes, before reviewing the combination of ultrasonic measurements and machine learning. We include literature from other sectors such as structural health monitoring. This review covers feature extraction, feature selection, algorithm choice, hyperparameter selection, data augmentation, domain adaptation, semi-supervised learning and machine learning interpretability. Finally, recommendations for applying machine learning to the reviewed processes are made.


The impact of lifestyle guidance intervention on health outcomes among Japanese middle-aged population with metabolic syndrome: A regression discontinuity study.
Metabolic syndrome (MetS) prevalence has increased globally with considerable morbidity and economic burden at both individual and national levels. Japan is the first and only country that has introduced a nationwide lifestyle guidance intervention program to manage and control MetS. We conducted a quasi-experiment approach-regression discontinuity design-to evaluate the impact of this intervention on health outcomes at the population level. We retrospectively collected data of adults aged ≥35 years who participated in health checkups in 2015. Age in 2015 was used as the assignment variable, and an age of 40 years old was the threshold because those with MetS aged ≥40 were required to receive lifestyle guidance intervention. Among 26,772 MetS adults, those who received the intervention had significant reductions in obesity measurements (bodyweight, waist circumference, and body mass index [BMI]) after 1 year of this intervention. Blood pressure was also significantly reduced in men after 1 year of undertaking the intervention. The results were similar when including demographic, socioeconomic, and behavioral covariates and using alternative functional forms to estimate the impact, or when bandwidths around intervention thresholds were changed. Our results showed that lifestyle guidance intervention for MetS has an important impact on weight loss and blood pressure reduction at the population level. This intervention could address the high burden of obesity and cardiovascular diseases in Japan and other countries with an unmet need for MetS prevention and management.


Pseudocohnilembus persalinus genome database - the first genome database of facultative scuticociliatosis pathogens.
Pseudocohnilembus persalinus, a unicellular ciliated protozoan, is one of commonest facultative pathogens. We sequenced the macronuclear genome of P. persalinus in 2015, which provided new insights into its pathogenicity. Here, we present the P. persalinus genome database (PPGD) ( http://ciliates.ihb.ac.cn/database/home/#pp ), the first genome database for the scuticociliatosis pathogens. PPGD integrates P. persalinus macronuclear genomic and transcriptomic data, including genome sequence, transcript, gene expression data, and gene annotation, as well as relevant information on its biology, morphology and taxonomy. The database also provides functions for visualizing, analyzing, and downloading the data. PPGD is a useful resource for studying scuticociliates or scuticociliatosis. We will continue to update the PPGD by integrating more data and aim to integrate the PPGD with other ciliate databases to build a comprehensive ciliate genome database.


Scapular renal cell carcinoma metastasis as a cause of high-output heart failure: a case report.
High-output heart failure is a rare condition that occurs when the heart is unable to respond to a sustained increase in blood demand. On echocardiography, a cardiac index of > 4 L/min/m2 (or 6 L/min) is a clear indicator of this disorder. The causes of high-output heart failure vary, but they all involve peripheral vasodilation or arteriovenous shunting. Renal cell carcinoma is well known for producing high levels of angiogenic growth factors that induce arteriovenous shunts. The decrease in peripheral arterial resistance and the increase in venous return result in a permanent high cardiac output, followed by congestive heart failure. Single bone metastases of renal clear cell carcinoma tumours causing high cardiac output and heart failure symptoms have been reported less than ten times in the medical literature. Before a right-shoulder painful lump with a murmur when auscultated, magnetic resonance imaging revealed a large scapular mass, which was biopsied and found to be a bone metastasis of renal cell carcinoma. Two months later, the patient developed heart failure for the first time. There was no evidence of cardiac disease on echocardiography. The cardiac output was 9.8 L/min and the cardiac index was 5.1 L/min/m2. Doppler ultrasound revealed numerous arteriovenous shunts in the large scapular metastasis and a right axillary artery flow of 24% of cardiac output. Sustained lower cardiac output was obtained following lesion-focused radiotherapy and systemic antiangiogenic treatment with axitinib and pembrolizumab. Herein, we present a unique case of high-output heart failure in a 70-year-old man diagnosed by echocardiography and upper-limb Doppler ultrasound in the context of metastatic renal cell carcinoma without pre-existing cardiac disease. We stress the potentially life-threatening hemodynamic consequences of hypervascularity associated with arteriovenous shunts within a single metastatic renal cell carcinoma implant, the importance of auscultating any progressing bone mass, and the utility of non-invasive Doppler ultrasound assessment in this setting.


Abnormal regional homogeneity as potential imaging biomarker for psychosis risk syndrome: a resting-state fMRI study and support vector machine analysis.
Subjects with psychosis risk syndrome (PRS) have structural and functional abnormalities in several brain regions. However, regional functional synchronization of PRS has not been clarified. We recruited 34 PRS subjects and 37 healthy controls. Regional homogeneity (ReHo) of resting-state functional magnetic resonance scans was employed to analyze regional functional synchronization in these participants. Receiver operating characteristic curves and support vector machines were used to detect whether abnormal regional functional synchronization could be utilized to separate PRS subjects from healthy controls. We observed that PRS subjects showed significant ReHo decreases in the left inferior temporal gyrus and increases in the right inferior frontal gyrus and right putamen compared with the controls. No correlations between abnormal regional functional synchronization in these brain regions and clinical characteristics existed. A combination of the ReHo values in the three brain regions showed sensitivity, specificity, and accuracy of 88.24%, 91.89%, and 90.14%, respectively, for discriminating PRS subjects from healthy controls. We inferred that abnormal regional functional synchronization exists in the cerebrum of PRS subjects, and a combination of ReHo values in these abnormal regions could be applied as potential image biomarker to identify PRS subjects from healthy controls.


Food restriction enhances peak corticosterone levels, cocaine-induced locomotor activity, and DeltaFosB expression in the nucleus accumbens of the rat.
Chronic stress has been known to potentiate addictive behaviours in both human addicts and experimental animals. In the present study, chronic mild food restriction was used as a stressor to investigate its effect on the locomotor simulant effects of cocaine as well as FosB expression in the nucleus accumbens and caudate putamen. Chronic mild food restriction enhanced the locomotor response to the first cocaine injection, such that chronically food restricted animals showed a significant increase in activity upon an initial administration of 15 mg/kg of cocaine, an effect which only became apparent in control animals after repeated injections. Food restriction also increased expression of the 35-37 kDa isoforms of DeltaFosB compared to free-fed rats. DeltaFosB proteins have been previously implicated in the rewarding effects of drugs of abuse and therefore their upregulation by the prolonged stress of food restriction suggests a possible mechanism for the enhancement of addictive behaviours by stress.


Detection of Behavioral Anomalies in Medication Adherence Patterns Among Patients With Serious Mental Illness Engaged With a Digital Medicine System.
Adherence to medication is often represented in the form of a success percentage over a period of time. Although noticeable changes to aggregate adherence levels may be indicative of unstable medication behavior, a lack of noticeable changes in aggregate levels over time does not necessarily indicate stability. The ability to detect developing changes in medication-taking behavior under such conditions in real time would allow patients and care teams to make more timely and informed decisions. This study aims to develop a method capable of identifying shifts in behavioral (medication) patterns at the individual level and subsequently assess the presence of such shifts in retrospective clinical trial data from patients with serious mental illness. We defined the term adherence volatility as "the degree to which medication ingestion behavior fits expected behavior based on historically observed data" and defined a contextual anomaly system around this concept, leveraging the empirical entropy rate of a stochastic process as the basis for formulating anomaly detection. For the presented methodology, each patient's evolving behavior is used to dynamically construct the expectation bounds for each future interval, eliminating the need to rely on model training or a static reference sequence. Simulations demonstrated that the presented methodology identifies anomalous behavior patterns even when aggregate adherence levels remain constant and highlight the temporal dependence inherent in these anomalies. Although a given sequence of events may present as anomalous during one period, that sequence should subsequently contribute to future expectations and may not be considered anomalous at a later period-this feature was demonstrated in retrospective clinical trial data. In the same clinical trial data, anomalous behavioral shifts were identified at both high- and low-adherence levels and were spread across the whole treatment regimen, with 77.1% (81/105) of the population demonstrating at least one behavioral anomaly at some point in their treatment. Digital medicine systems offer new opportunities to inform treatment decisions and provide complementary information about medication adherence. This paper introduces the concept of adherence volatility and develops a new type of contextual anomaly detection, which does not require an a priori definition of normal and allows expectations to evolve with shifting behavior, removing the need to rely on training data or static reference sequences. Retrospective analysis from clinical trial data highlights that such an approach could provide new opportunities to meaningfully engage patients about potential shifts in their ingestion behavior; however, this framework is not intended to replace clinical judgment, rather to highlight elements of data that warrant attention. The evidence provided here identifies new areas for research and seems to justify additional explorations in this area.


The prognostic significance of the air volume in the middle ear for the tendency to recurrence of secretory middle ear condition.
The incidence of recurrence of secretory middle ear conditions (SMEC) in the course of the first 3 months after extrusion of a grommet was evaluated in 172 tubulated patients in relation to a number of background variables in a stepwise logistic regression analysis. The background variables were: treatment period, 3-month period (season) of extrusion, sex, age, air volume in the middle ear, diagnosis (unilateral/bilateral, suppurative/non-suppurative and consequently antibiotics), other treatment apart from a grommet (paracentesis and/or adenoidectomy), and a history of allergy. There was a definite correlation between the incidence of recurrence and the air volume in the middle ear, as determined by physical volume test, after correction for age, recurrences being most common in ears with a small middle ear volume. In addition, there was a relationship, but not as marked, between the incidence of recurrence and age after correction for the middle ear volume, recurrences being less common in older patients. None of the other background variables played a statistically significant role when correction was made for age and middle ear volume. It is recommended to practise an expectant therapeutic strategy in SMEC in order to eliminate cases with spontaneous remission. In the event of recurrence, a more liberal reinsertion of grommets is recommended for patients with small middle ear volumes, while in those with larger volumes a different aetiology should possibly be considered.


Long-term study on wastewater SARS-CoV-2 surveillance across United Arab Emirates.
Wastewater-based epidemiology (WBE) demonstrates an efficient tool to monitor and predict SARS-CoV-2 community distribution. Many countries across the world have adopted the technique, however, most of these studies were conducted for a short duration with a limited sampling size. In this study, long-term reliability and quantification of wastewater SARS-CoV-2 surveillance is reported via analyzing 16,858 samples collected from 453 different locations across the United Arab Emirates (UAE) from May 2020 to June 2022. The collected composite samples were first incubated at 60 °C followed by filtration, concentration, and then RNA extraction using commercially available kits. The extracted RNA was then analyzed by one-step RT-qPCR and RT-ddPCR, and the data was compared to the reported clinical cases. The average positivity rate in the wastewater samples was found to be 60.61 % (8.41-96.77 %), however, the positivity rate obtained from the RT-ddPCR was significantly higher than the RT-qPCR suggesting higher sensitivity of RT-ddPCR. Time-lagged correlation analysis indicated an increase in positive cases in the wastewater samples when the clinical positive cases declined suggesting that wastewater data are highly affected by the unreported asymptomatic, pre-symptomatic and recovering individuals. The weekly SARS-CoV-2 viral count in the wastewater samples are positively correlated with the diagnosed new clinical cases throughout the studied period and the studied locations. Viral count in wastewater peaked approximately one to two weeks prior to the peaks appearing in active clinical cases indicating that wastewater viral concentrations are effective in predicting clinical cases. Overall, this study further confirms the long-term sensitivity and robust approach of WBE to detect trends in SARS-CoV-2 spread and helps contribute to pandemic management.


The association of denture stomatitis and partial removable dental prostheses: a systematic review.
The aim of this systematic review was to analyze the evidence on the occurrence of denture stomatitis (DS) and potential risk factors in patients wearing partial removable dental prostheses (RDPs). MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews were searched and complemented by manual searching. Outcome measures were the presence of DS in patients wearing partial RDPs and an assessment of associated risk factors. All types of experimental and observational studies investigating an association between DS and the wearing of partial RDPs were included. Methodologic quality and level of evidence were assessed using valid scales. Two authors performed study selection, data extraction, and quality assessment independently. A total of eight studies met the inclusion criteria. The prevalence of DS in partial RDP wearers ranged from 1.1% to 36.7%. Data on the potential risk factors were not consistent. Despite the heterogeneity and methodologic quality of included studies, an association between DS and the wearing of partial RDPs was found. There is some evidence that the presence of DS is associated with the wearing of partial RDPs. However, because of methodologic limitations and cross-sectional designs of research studies, no cause-effect relationship could be inferred. Future research should provide higher levels of evidence to confirm the etiology of DS in partial RDP wearers.


Contemporary Patterns of Medicare and Medicaid Utilization and Associated Spending on Sacubitril/Valsartan and Ivabradine in Heart Failure.
In 2015, the US Food and Drug Administration approved 2 new medications for treatment of heart failure with reduced ejection fraction, sacubitril/valsartan and ivabradine. However, few national data are available examining their contemporary use and associated costs. To evaluate national patterns of use of sacubitril/valsartan and ivabradine and associated therapeutic spending in Medicare Part D and Medicaid. In this US nationwide claims-based study, we analyzed data from the Medicare Part D Prescription Drug Event and Medicaid Utilization and Spending data sets to compare national patterns of use of sacubitril/valsartan and ivabradine between 2016 and 2017. Changes in total spending, per-beneficiary/claim spending, number of beneficiaries, and number of claims between 2016 and 2017 for sacubitril/valsartan and ivabradine. The number of Medicare beneficiaries prescribed sacubitril/valsartan increased from 35 423 to 90 606 (156% increase from 2016 to 2017). Medicare beneficiaries prescribed ivabradine increased from 15 856 to 23 213 (46% increase). In 2017, Medicare Part D spent $227 million and $7.3 million on sacubitril/valsartan and ivabradine, respectively. This represented increases of 241% and 59% compared with 2016 spending, respectively. The annual Medicare per-beneficiary spending on sacubitril/valsartan and ivabradine was $2512 and $2400. Parallel trends in use patterns and spending were observed among Medicaid beneficiaries. Although initial experiences suggested slow uptake after regulatory approval, these national data demonstrate an increase in use of sacubitril/valsartan and, to a lesser degree, ivabradine in the United States. Current annual per-beneficiary expenditures remain less than spending thresholds that have been reported to be cost-effective. Ongoing efforts are needed to promote high-value care while improving affordability and access to established and emerging heart failure therapies.


[Incidence of reopening and variables that influence reopening after macular hole surgery].
To evaluate the incidence and variables of reopening of macular holes after macular hole surgery. Our study included 467 eyes in which maculor holes were successfully closed after surgery. Surgical techniques consisted of conventional methods (358 eyes) and scalping methods (109 eyes) with retinal pigment scalping of the macular hole basis added in such cases: reoperation, hole size (more than 0.4 disc diameter), duration of symptoms (more than 2 years). Long term incidence of reopening was predicted by life table method. After we compared reopened cases with non-reopened cases, the variables of gender, stage, biocular occurrence, age, duration of symptoms, hole size, preoperative visual acuity, refraction axial length ratio, and intraoperative retinal tears were used for the multiple regression. Reopening was found in 20 eyes (5.6%) treated by conventional methods and in 10 eyes (9.2%) treated by scalping methods. Survival ratio was 87% for the conventional methods in 6 years and 79% for the scalping methods in 5 years. The variables influencing reopening were as follows: conventional methods: gender (r = 0.065, p = 0.19), biocular occurrence (r = 0.12, p = 0.026), and refraction axial length ratio (r = -0.11, p = 0.045); scalping methods: hole size (r = 0.14, p = 0.25). Incidence of reopening in scalping methods was high. The variables that influenced reopening after macular hole surgery were biocular occurrence and refraction axial length ratio in conventional methods. The shape of the eye may be related to reopening.


Breast Cancer Risk in Women from Ghana Carrying Rare Germline Pathogenic Mutations.
Risk estimates for women carrying germline mutations in breast cancer susceptibility genes are mainly based on studies of European ancestry women. We investigated associations between pathogenic variants (PV) in 34 genes with breast cancer risk in 871 cases [307 estrogen receptor (ER)-positive, 321 ER-negative, and 243 ER-unknown] and 1,563 controls in the Ghana Breast Health Study (GBHS), and estimated lifetime risk for carriers. We compared results with those for European, Asian, and African American ancestry women. The frequency of PV in GBHS for nine breast cancer genes was 8.38% in cases and 1.22% in controls. Relative risk estimates for overall breast cancer were: (OR, 13.70; 95% confidence interval (CI), 4.03-46.51) for BRCA1, (OR, 7.02; 95% CI, 3.17-15.54) for BRCA2, (OR, 17.25; 95% CI, 2.15-138.13) for PALB2, 5 cases and no controls carried TP53 PVs, and 2.10, (0.72-6.14) for moderate-risk genes combined (ATM, BARD1, CHEK2, RAD51C, RAD52D). These estimates were similar to those previously reported in other populations and were modified by ER status. No other genes evaluated had mutations associated at P < 0.05 with overall risk. The estimated lifetime risks for mutation carriers in BRCA1, BRCA2, and PALB2 and moderate-risk genes were 18.4%, 9.8%, 22.4%, and 3.1%, respectively, markedly lower than in Western populations with higher baseline risks. We confirmed associations between PV and breast cancer risk in Ghanaian women and provide absolute risk estimates that could inform counseling in Ghana and other West African countries. These findings have direct relevance for breast cancer genetic counseling for women in West Africa.


Linking Community OPR and Communication Infrastructure During a Public Health Crisis: A Study of Community Engagement in Shanghai, China.
Engaging the public and community organizations in local health actions greatly assists disease prevention and control. However, it remains unclear how organization-public relationships (OPR) and communication networks within communities contribute to community health actions. To fill this gap, a survey was conducted among community members in Shanghai, China, who were challenged by the Omicron wave of the COVID-19 pandemic. Results revealed that integrated connectedness to a storytelling network (ICSN) was a significant predictor of residents' community engagement. Trust, control mutuality, commitment, and ICSN were positively associated with community engagement intentions through the sense of community and organizational efficacy. This study is a step toward understanding how organizations and members collectively respond to health crises at the community level.


Effect of dofetilide on QT dispersion and the prognostic implications of changes in QT dispersion for patients with congestive heart failure.
Drug-induced changes in QT dispersion may be a way of detecting harmful repolarisation abnormalities for patients receiving antiarrhythmic drugs affecting ventricular repolarisation. In 463 congestive heart failure (CHF) patients enrolled in the Danish Investigations Of Arrhythmia and Mortality On Dofetilide-CHF (DIAMOND-CHF) study, both pre-treatment and on-treatment day 2-6 QT dispersion was available from standard 12-lead ECGs. Patients were randomised in a double-blind manner to receive either placebo or dofetilide, a new class III antiarrhythmic drug. During a median follow-up of 19 months (minimum 1 year), 179 patients (39%) died (135 patients from cardiac causes). Changes in QT dispersion did not predict all-cause or cardiac mortality for patients treated with dofetilide in multivariate survival analysis (Risk ratio: 1.02, 95% confidence interval: 0.97-1.08, P>0.4). This finding was independent of pre-treatment QT dispersion. Dofetilide caused a small QT dispersion increment of 8 ms, not different from the changes seen in the placebo group (3 ms). For patients with CHF and reduced left ventricular systolic function, changes in QT dispersion following treatment with dofetilide do not predict all-cause or cardiac mortality. The dofetilide-induced QT dispersion changes are small and comparable to those seen in placebo treated patients.


Coexpression of glucagon-like peptide-1 (GLP-1) receptor, vasopressin, and oxytocin mRNAs in neurons of the rat hypothalamic supraoptic and paraventricular nuclei: effect of GLP-1(7-36)amide on vasopressin and oxytocin release.
This study was designed to gain better insight into the relationship between glucagon-like peptide-1 (GLP-1) (7-36) amide and vasopressin (AVP) and oxytocin (OX). In situ hybridization histochemistry revealed colocalization of the mRNAs for GLP-1 receptor, AVP, and OX in neurons of the hypothalamic supraoptic and paraventricular nuclei. To determine whether GLP-1(7-36)amide alters AVP and/or OX release, both in vivo and in vitro experimental study designs were used. In vivo, intravenous administration of 1 microg of GLP-1(7-36)amide into the jugular vein significantly decreased plasma AVP and OX concentrations. In vitro incubation of the neurohypophysis with either 0.1 or 1 microg of GLP-1(7-36)amide did not modify the release of AVP. However, addition of 1 microg of GLP-1(7-36)amide to the incubation medium increased slightly the secretion of OX. The coexpression of GLP-1 receptor and AVP mRNAs in hypothalamic supraoptic and paraventricular nuclei gives further support to the already reported central effects of GLP-1 (7-36)amide on AVP. Our findings also suggest a dual secretory response of AVP and OX to the effect of GLP-1 (7-36)amide, which most likely is related to the amount and/or the route of peptide administration.


Association of alcohol consumption with the incidence of proteinuria and chronic kidney disease: a retrospective cohort study in Japan.
The difference in the clinical impact of alcohol consumption on kidney function based on sex remains to be elucidated. This study aimed to assess the association between the dose of alcohol consumption and the incidence of proteinuria and chronic kidney disease stratified by sex. This retrospective cohort study included 26,788 workers (19,702 men and 7086 women) with normal renal function (estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2) at annual health examinations between January 2010 and March 2015 in Japan. The main exposure was alcohol consumption. The primary outcomes were the incidence of proteinuria (dipstick urinary protein ≥ 1) and incidence of low estimated glomerular filtration rate (eGFR; rate < 60 mL/min per 1.73 m2; decreased from the baseline eGFR by 25%). During a median observational period of 4 years (interquartile range: 2-6), 1993 (10.1%) men and 462 (6.5%) women developed proteinuria, whereas 667 (3.4%) men and 255 (3.6%) women developed low eGFR. After adjustment for clinically relevant factors using a Cox proportional hazards model, alcohol consumption of ≥ 46 g/day in females was significantly associated with the incidence of proteinuria (hazard ratio, 1.57; 95% confidence interval, 1.10-2.26) and low eGFR (hazard ratio, 1.62; 95% confidence interval, 1.04-2.53). However, no significant association between alcohol consumption and primary outcomes was observed in men. In conclusion, daily higher alcohol consumption was significantly associated with a higher incidence of proteinuria and low eGFR among women. Women might be prone to high alcohol consumption with kidney dysfunction.


Structure of polypoidal choroidal vasculopathy studied by colocalization between tomographic and angiographic lesions.
To investigate the structure of polypoidal choroidal vasculopathy (PCV) by tomographic localization of the branching vascular network and late geographic hyperfluorescence. Observational case series. We examined 34 eyes with PCV by simultaneous indocyanine green angiography (ICGA) and spectral-domain optical coherence tomography (OCT) imaging. The margin of the branching vascular network and the late geographic hyperfluorescence on ICGA was colocalized on OCT, in a point-to-point manner, using innate software. The large vessels within the branching vascular network were also colocalized on OCT. Late geographic hyperfluorescence on ICGA was noted in 30 eyes. The extent of late geographic hyperfluorescence was larger than that of branching vascular network in 12 eyes. In the remaining eyes, the extent was the same. A double-layer sign on OCT, which consisted of two hyper-reflective lines, representing the retinal pigment epithelium and Bruch membrane, was noted in 29 eyes. In all 28 eyes exhibiting both late geographic hyperfluorescence and the double-layer sign, the extent of late geographic hyperfluorescence matched exactly the extent of double-layer sign on OCT. In 7 of 34 eyes, the thickness of the subretinal pigment epithelial space over the Bruch membrane was too thin to accommodate the large vessels of the branching vascular network. Although the double-layer sign showed mild reduction in area after photodynamic therapy, its general configuration was maintained. Late geographic hyperfluorescence on ICGA corresponds with the double-layer sign on OCT in eyes with PCV. Our observations suggest that the double-layer sign consists mainly of fibrous tissue harbored by the branching vascular network, and late geographic hyperfluorescence may originate from the staining of tissue.


Cardiac papillary fibroelastoma of the mitral chorda.
We describe a case of cardiac papillary fibroelastoma in a 33-year-old man. The diagnosis was established by echocardiography. Computerised tomographic angiography gave no evidence of coronary stenosis, but illustrated a radiopaque filling defect in the left ventricle. The papillary fibroelastoma was removed together with the involved chorda, and an artificial chord was implanted under cardiopulmonary bypass. Histological study confirmed the diagnosis of papillary fibroelastoma. Due to the potentials of cerebral and coronary embolisation, surgical management to the patients with a papillary fibroelastoma is highly recommended.


Temperature and water relation patterns in subalpine understory plants.
The daily temperature and water relations of 7 perennial subalpine, understory species (1 shrub, 1 subshrub, 5 herbs) were compared in the Rocky Mountains of southeastern Wyoming with an emphasis on the effects of natural sun and shade exposure. Field measurements of rainfall; leaf, air, and soil temperatures; stomatal conductance to water vapor diffusion; and plant and soil water potentials were supplemented with leaf and root morphological measurements to evaluate potential adaptive patterns in understory species.Morphologically, all 7 species had relatively broad leaves that were hypostomous and bicolored with the abaxial leaf surface lighter than the abaxial surface. Root systems tended to be shallow (<20 cm), especially for the herbaceous species. Although soil water potentials from 4 to 40 cm depths remained relatively high throughout the summer (>-1.0 MPa), plant xylem water potentials for sunlit plants decreased to below-2.0 MPa during midday. During these sunlit periods, leaf temperatures and conductances increased substantially, leading to severe wilting for 4 of the 5 herbaceous species. Stomatal conductance and density for 6 of the 7 species monitored were much greater on abaxial compared to adaxial leaf sides and substantial stomatal closure occurred when either leaf side was oriented to receive direct sunlight. Moreover, stomatal opening on abaxial leaf sides corresponded to the amount of sunlight incident upon the adaxial rather than abaxial leaf surfaces. The 2 shrubby species did not wilt during these periods and were characterized by the highest leaf temperatures (>30°C). These 2 species also had consistantly lower xylem water potentials throughout the summer growth period. These results are discussed in terms of the possible adaptive significance of midday wilting, leaf hypostomy and bicoloration and stomatal behavior to the water and photosynthetic relations of understory species.


High-frequency switching in Candida albicans and its relations to vaginal candidiasis.
Candida albicans possesses the ability to switch reversibly and at high frequency between a number of heritable phenotypes distinguishable by colony morphology and in some cases cellular phenotype. In the original switching system identified in C. albicans, it was demonstrated that cells could switch at frequencies as high as 10(-2) among seven distinct colony phenotypes including smooth, star, ring, stipple, irregular wrinkle, hat, and fuzzy. In a second switching system first discovered in a systemic infection, cells switched at high frequency between a white and an opaque colony former. Recently, switching was discovered in isolates from patients with vaginal candidiasis and multiple switch phenotypes were cloned from an individual vagina. Switching may contribute to the pathogenesis of C. albicans by providing it with the capacity to invade diverse sites in the body, to change resistance to antifungal agents, or to change antigenicity. The molecular basis of switching is probably due to the reversible transposition or rearrangement of genomic elements, although a direct correlation between recently identified genomic rearrangements and phenotypic switching has not been made.


Preparation of stretchable and self-healable dual ionically cross-linked hydrogel based on chitosan/polyacrylic acid with anti-freezing property for multi-model flexible sensing and detection.
As a kind of promising material for flexible wearable electronics, conductive hydrogels have attracted extensive interests of researchers for their inherent merits such as superior mechanical properties, biocompatibility, and permeability. Herein, we constructed a new type of highly stretchable, anti-freezing, self-healable, and conductive hydrogel based on chitosan/polyacrylic acid. The large amount of ions inside the network had five functions for the proposed hydrogel, including excellent mechanical behaviors, high conductivity, self-recovery, self-healing and anti-freezing capability. Consequently, the proposed hydrogel possessed tunable stretchability (1190-1550%), tensile strength (0.96-2.56 MPa), toughness (5.7-14.7 MJ/m3), superior self-healing property (self-healing efficiency up to 83.7%), high conductivity (4.58-5.76 S/m), and excellent anti-freezing capability. To our knowledge, the self-healable hydrogel with balanced tensile strength, toughness, conductivity, and low-temperature tolerance can hardly be achieved till now. Furthermore, the conductive hydrogels exhibited high sensitivity (gauge factor up to 10.8) in a broad strain window (0-1000%) and could detect the conventional motion signals of human body such as bending of a knuckle, swallowing, and pressure signal at both room temperature and -20 °C. Moreover, the hydrogels could also be fabricated as flexible detectors to identify different temperatures, different kinds of solutions, and different concentrations of the solution.


Influences of experimental factors on spinal stretch reflex latency and amplitude in the human triceps surae.
The spinal stretch reflex (SSR) is commonly assessed via electromyographic (EMG) analysis of joint perturbations inducing changes in muscle length. Previous literature indicates that when large experimental changes in magnitude of agonist background EMG, perturbation velocity, and perturbation amplitude are employed, SSR latency and amplitude are significantly altered. The purpose of this investigation was to evaluate the relative dependence of SSR latency and amplitude on inherent variability in these experimental variables. Soleus SSR latency and amplitude were assessed in 40 healthy subjects following dorsiflexion perturbation under an active state ( approximately 14% MVC). Experimental variables displayed limited variability (means +/- SD): soleus background EMG (13.47 +/- 7.08% MVC), perturbation velocity (96.1 +/- 30 degrees /s), and perturbation amplitude (4 +/- 1 degrees ). SSR latency was not significantly related to soleus background EMG (r = 0.189), perturbation velocity (r = 0.213), or perturbation amplitude (r = 0.202). Similarly, SSR amplitude was not significantly related to soleus background EMG (r = 0.306), perturbation velocity (r = 0.053), or perturbation amplitude (r = 0.056). Variability in experimental variables was much smaller than what has been reported in the literature to significantly impact SSR characteristics. These results suggest that SSR latency and amplitude are independent of agonist background EMG, perturbation velocity, and perturbation amplitude when experimental variability is relatively limited.


The interns' learning assessment in obstetrics and gynecology department of Zahedan University of Medical Sciences.
One of the aims of management priorities in medical universities is the evaluation of learning in educational departments in order to prevent educational retardation and to improve the quality of education. The aim of this study was to evaluate the interns' learning in the obstetrics and gynecology (O&G) department at Zahedan University of Medical Sciences (ZUMS). The study was performed in ZUMS, Iran, in 2002-2003 on all interns at the O&G department, including 30 men and 40 women. For data collection, a questionnaire was used and included some questions regarding the common emergencies and diseases in O&G, together with different learning indicators such as reading, observation, hearing, management, and the capability of management. The data were analyzed using descriptive statistics, tables, t test, and chi-square test using the SPSS software. The mean percentages of learning indicators of observation, bedside teaching, supervised management, and personal management in the common emergencies and diseases of O&G in male interns were significantly lower than those in female interns. Also, the mean percentages of managing capabilities were 12% and 70.5% in common emergencies and 14.2% and 59.3% in common diseases for male and female interns, respectively. The chi-square test showed a significant difference between the mean percentages of the managing capabilities in male and female interns for the majority of the common emergencies and diseases. Also, the chi-square test revealed a significant relationship between the learning indicators and the interns' managing capabilities for common emergencies and diseases. Some learning indicators in the male interns were very low. This needs urgent improvement of the learning quality in the O&G department, especially for the male interns, particularly those who are supposed to work in the deprived areas of the country after graduation in the public service.


N-acetylgalactosamine (GalNAc) transfer to the common carbohydrate-protein linkage region of sulfated glycosaminoglycans. Identification of UDP-GalNAc:chondro-oligosaccharide alpha-N-acetylgalactosaminyltransferase in fetal bovine serum.
During the course of a study of elucidate the role of modification of the common polysaccharide-protein linkage structure, GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl beta 1-O-Ser, in biosynthetic sorting mechanisms of the different sulfated glycosaminoglycan chains, a novel N-acetylgalactosamine (GalNAc) transferase was discovered in fetal bovine serum. The enzyme catalyzed the transfer of [3H]GalNAc from UDP-[3H]GalNAc to linkage tetrasaccharide and hexasaccharide serines synthesized chemically and to various regular oligosaccharides containing terminal D-glucuronic acid (GlcA), which were prepared from chondroitin and chondroitin sulfate using testicular hyaluronidase digestion. The labeled products obtained with the linkage tetra- and hexasaccharide serines and with the tetrasaccharide (GlcA beta 1-3GalNAc)2 were resistant to digestion with chondroitinase AC-II and beta-N-acetylhexosaminidase but sensitive to alpha-N-acetylgalactosaminidase digestion, indicating that the enzyme is an alpha-N-acetylgalactosaminyltransferase. This finding is in contrast to that of Rohrmann et al. (Rohrmann, K., Niemann, R., and Buddecke, E. (1985) Eur. J. Biochem., 148, 463-469), who reported that a corresponding product was susceptible to digestion with beta-N-acetylhexosaminidase. The presence of a sulfate group at C4 of the penultimate GalNAc or Gal units markedly inhibited the transfer of GalNAc to the terminal GlcA, while a sulfate group at C6 of the GalNAc had little effect on the transfer. Moreover, a slight but significant transfer of [3H]GalNAc was observed to an oligosaccharide containing terminal 2-O-sulfated GlcA as acceptor, whereas no incorporation was detected into oligosaccharides containing terminal unsaturated or 3-O-sulfated GlcA units. These results suggest that this novel serum enzyme is a UDP-GalNAc:chondro-oligosaccharide alpha 1-3- or 1-4-N-acetylgalactosaminyltransferase. The possibility of involvement of this enzyme in glycosaminoglycan biosynthesis is discussed.


Neural stem cells injured by oxidative stress can be rejuvenated by GV1001, a novel peptide, through scavenging free radicals and enhancing survival signals.
Oxidative stress is a well-known pathogenic mechanism of a diverse array of neurological diseases, and thus, numerous studies have attempted to identify antioxidants that prevent neuronal cell death. GV1001 is a 16-amino-acid peptide derived from human telomerase reverse transcriptase (hTERT). Considering that hTERT has a strong antioxidant effect, whether GV1001 also has an antioxidant effect is a question of interest. In the present study, we aimed to investigate the effects of GV1001 against oxidative stress in neural stem cells (NSCs). Primary culture NSCs were treated with different concentrations of GV1001 and/or hydrogen peroxide (H2O2) for various time durations. The H2O2 decreased the viability of the NSCs in a concentration-dependent manner, with 200μM H2O2 significantly decreasing both proliferation and migration. However, treatment with GV1001 rescued the viability, proliferation and migration of H2O2-injured NSCs. Consistently, free radical levels were increased in rat NSCs treated with H2O2, while co-treatment with GV1001 significantly reduced these levels, especially the intracellular levels. In addition, GV1001 restored the expression of survival-related proteins and reduced the expression of death-associated ones in NSCs treated with H2O2. In conclusion, GV1001 has antioxidant and neuroprotective effects in NSCs following treatment with H2O2, which appear to be mediated by scavenging free radicals, increasing survival signals and decreasing death signals.


Pregnancy in homozygous familial hypercholesterolemia--Importance of LDL-apheresis.
Rare cases of pregnancy in women with homozygous familial hypercholesterolemia (HFH) have been reported. HFH might pose significant risks for the mother and her fetus. Statins, the most potent agents for low-density lipoprotein (LDL) cholesterol reduction, are contraindicated; thus lipoprotein apheresis remains the only effective treatment. We report on a 34-year-old pregnant woman with HFH who was treated throughout the entire pregnancy by lipoprotein apheresis (immunoadsorption method). Increasing levels of LDL-cholesterol were stabilized at 9-10 mmol/L by lipoprotein apheresis (performed every 10 days). No complications were observed during the treatment procedures. Monitoring of the fetus revealed no impairment of the umbilical cord and blood flow in the uterine arteries, as well as no intrauterine growth retardation. The delivery was spontaneous and the child was breastfed for two months. Intensive treatment by lipoprotein apheresis is an effective and safe therapeutic strategy during pregnancy, even in severe cases of HFH, as it can stabilize progressively increasing lipoprotein levels and prevent severe complications.


Immunopathological characterization of the delayed hypersensitivity skin reaction to carrier protein.
Characteristics of the allergic skin reaction to free carrier protein in sensitized guinea pig with hapten-carrier conjugate have been studied. The animals sensitized with a low dose (4 micrograms) of dinitrophenylated bovine gamma globulin with Freund's complete adjuvant demonstrated a dermatitis when challenged intradermally with a small dose (10 micrograms) of bovine gamma globulin on the 10th or 14th day. The dermatitis was grossly and histologically similar to the classical form of delayed-type hypersensitivity skin reaction except lesser induration and less abundant neutrophil infiltration in the former. This reaction was clearly different from cutaneous basophil hypersensitivity because of the long lasting time course and fewer basophil infiltration in the former. No humoral antibody to carrier protein was detected in the sera of the sensitized animals by passive cutaneous anaphylaxis or by immunodiffusion in agar plates, and the state of the hypersensitivity could be passively transferred with peritoneal exudate cells and spleen cells. These observations indicated that the skin reaction to carrier protein might be of primarily delayed-type hypersensitivity. The vascular permeability change at the reaction sites was observed as a single phase delayed response and preceded the maximum erythema by about ten hours.


Identification of novel lncRNAs associated with sensitivity of HIV antiretroviral therapy: A two-stage matched case-control study.
To identify long non-coding RNAs (lncRNAs) that may be used as potential biomarkers of sensitivity to antiretroviral therapy (ART) against human immunodeficiency virus (HIV) infection. A two-stage matched case-control study was conducted. First, in the screening stage, peripheral blood lymphocytes (PBLs) of six subjects receiving lamivudine-based ART (3 ART-resistant and 3 ART-sensitive subjects with matching durations of ART) were subjected to comprehensive microarray expression profiling in order to screen out lncRNAs associated with ART sensitivity. Secondly, during the validation stage, promising lncRNAs were evaluated via a 1:4 matched case-control study using 50 subjects (10 ART-resistant and 40 ART-sensitive subjects with matching durations of ART). Seven lncRNAs were screened out (P < 1.06 × 10-3) in the first stage. Among these, two lncRNAs (n341598 and n407911) survived validation conducted at the second stage (n341598: P < 0.001; n407911: P = 0.007), while another lncRNA n406445 showed marginally significant (P = 0.049). All three showed higher expression in ART-resistant subjects compared to that in ART-sensitive subjects. The area under the ROC curve (AUC) for n341598 was 0.867 (95 % CI: 0.796-0.966; P < 0.001), which was better than that for n406445 (0.702) and n407911 (0.780). Meanwhile, the AUC for n341598 was better than that of any combination of the three lncRNAs. Our study identified three highly expressed lncRNAs in patients with HIV ART-resistant, among which the lncRNA n341598 may be utilized as an optimal biomarker to distinguish ART-resistant and ART-sensitive patients. Further studies aimed at revealing the molecular mechanisms underlying the regulation of ART sensitivity by n341598 are warranted to complement our findings.


[Metabolism of somatotropin in severe liver diseases. Influence of the therapeutic administration of a liver extract].
Metabolic Clearance Rate (MCR) and half life of 125I Human Growth Hormone (HGH) have been studied in hepatopathic patients. A clear reduction of MCR and a prolongation of HGH half life have been found in all patients examined. After a 30 day therapy with crude liver extract (F.U. VIII ed.) both MCR and HGH half life have shown a tendency towards normalization. These findings are in agreement with the marked improvement of the clinical state of the patients and with the normalization of the laboratory indexes.


Nitrous oxide concentrations in maternal and fetal blood during caesarean section.
There are little data on nitrous oxide (N2O) concentrations in neonatal blood at delivery. We investigated the effects of the time elapsing between the induction of anaesthesia and delivery (the I-D interval) on umbilical blood N2O concentrations. Maternal and neonatal blood N2O concentrations were measured in 27 patients undergoing Caesarean section under N2O 67% anaesthesia. The duration of N2O administration (range 2-50 min) was arbitrarily divided into three groups (each n = 9): short (2-9 min), medium (9.1-14 min) and long duration (14.1-50 min). Compared with a rapid increase in the maternal arterial N2O concentration (48.9 +/- 4.7%), the umbilical venous N2O concentration (17.9 +/- 8.3%) rose slowly in the short duration group, whereas the N2O concentrations became more similar (61.6 +/- 4.3 and 43.2 +/- 10.0%, respectively) in the long duration group. The ratio of umbilical vein to maternal artery N2O concentrations correlated with the duration of N2O anaesthesia (r = 0.739), resulting in ratios of 0.37 +/- 0.18, 0.61 +/- 012 and 0.70 +/- 0.13 for the short, medium and long duration groups, respectively. The Apgar score at 1 min correlated inversely with the duration of anaesthesia and with the umbilical vein N2O concentration (r = -0.457 and -0.423, respectively). The data suggest that placental N2O transfer during Caesarean section is time-dependent and slower compared with maternal N2O uptake. They also suggest that the Apgar score is less affected by N2O administration when the I-D interval is shorter.


In vitro studies on the metabolism of dibenzo[c,f]-[1,2]diazepine.
Dibenzo [c,f]-[1,2] diazepine is a new compound with a tricyclic structure and a double bond between two nitrogen atoms in positions 1 and 2 of the molecule. Its in vitro metabolism has been studied, incubating the compound with rat liver microsomes. Two metabolites have been identified: dibenzo [c,f] - [1,2]diazepine-1-N-oxide and a monohydroxyderivative in the aromatic ring.


Diffuse retinal dysfunction following immune reconstitution uveitis in patients with prior cytomegalovirus retinitis: a novel observation.
To report continuing diffuse retinal dysfunction following resolution of immune reconstitution uveitis (IRU) in patients with cytomegalovirus retinitis (CMVR). Retrospective case series describing two patients with IRU following CMVR who underwent serial fundus photography and macular optical coherence tomography. One patient had serial electrophysiology. Both patients had CMVR successfully treated with antiviral medication. The affected eyes later developed IRU that resolved with steroids. However, following resolution, chronic retinal damage was evidenced by ellipsoid line loss in one case and gradual optic disc cupping in the other. Electrophysiology in both cases revealed generalized retinal dysfunction worse in the eye with more severe IRU and demonstrated objectively the efficacy of treatment intervention in the patient with serial recordings. Patients with IRU following CMV retinitis may have continuing diffuse retinal dysfunction despite apparent recovery and normal visual acuity. An aggressive approach to inflammation control may be warranted in such patients.


European semi-anthropomorphic spine phantom for the calibration of bone densitometers: assessment of precision, stability and accuracy. The European Quantitation of Osteoporosis Study Group.
Up to now it has not been possible to reliably cross-calibrate dual-energy X-ray absorptiometry (DXA) densitometry equipment made by different manufacturers so that a measurement made on an individual subject can be expressed in the units used with a different type of machine. Manufacturers have adopted various procedures for edge detection and calibration, producing various normal ranges which are specific to each individual manufacturer's brand of machine. In this study we have used the recently described European Spine Phantom (ESP, prototype version), which contains three semi-anthropomorphic "vertebrae" of different densities made of stimulated cortical and trabecular bone, to calibrate a range of DXA densitometers and quantitative computed tomography (QCT) equipment used in the measurement of trabecular bone density of the lumbar vertebrae. Three brands of QCT equipment and three brands of DXA equipment were assessed. Repeat measurements were made to assess machine stability. With the large majority of machines which proved stable, mean values were obtained for the measured low, medium and high density vertebrae respectively. In the case of the QCT equipment these means were for the trabecular bone density, and in the case of the DXA equipment for vertebral body bone density in the posteroanterior projection. All DXA machines overestimated the projected area of the vertebral bodies by incorporating variable amounts of transverse process. In general, the QCT equipment gave measured values which were close to the specified values for trabecular density, but there were substantial differences from the specified values in the results provided by the three DXA brands. For the QCT and Norland DXA machines (posteroanterior view), the relationships between specified densities and observed densities were found to be linear, whereas for the other DXA equipment (posteroanterior view), slightly curvilinear, exponential fits were found to be necessary to fit the plots of observed versus specified densities. From these plots, individual calibration equations were derived for each machine studied. For optimal cross-calibration, it was found to be necessary to use an individual calibration equation for each machine. This study has shown that it is possible to cross-calibrate DXA as well as QCT equipment for the measurement of axial bone density. This will be of considerable benefit for large-scale epidemiological studies as well as for multi-site clinical studies depending on bone densitometry.


Use of gas liquid chromatography/mass spectrometry for triazine herbicide residues analysis in forage and milk.
Residual s-triazines were isolated from forage and milk samples by methanol/chloroform extraction followed by column purification. The evaporated extracts were dissolved in acetone and analysed by gas chromatography with NPD detection and mass spectrometry. The detection limits for both methods were found to be about 5 approximately 10 ng of each s-triazine. The selective ions of the 10 s-triazines investigated (simazine, atrazine, propazine, terbuthylazine, cyanazine, desmetryne, ametryne, prometryne, terbutryne and methoprotryne) were chosen on the basis of an electron impact mass spectrometry study of the s-triazine standards and the whole mass spectra are given. Special attention was paid to the fragmentation of cyanazine and the general cleavage pathways of the s-triazines under investigation.


Neurochemical and behavioral consequences of acute, uncontrollable stress: effects of dietary tyrosine.
Acute, uncontrollable stress increases norepinephrine (NE) turnover in the rat's brain (thereby depleting NE) and diminishes the animal's subsequent tendency to explore a novel environment. We determined whether supplemental dietary tyrosine could prevent some of these changes. Rats given a control diet or diets enriched with tyrosine or tyrosine plus valine were exposed to tail-shock stress or to no stress over a 60-min period. Exposure to the stress caused an increase in NE turnover, decreasing NE and increasing 3-methoxy-4-hydroxy-phenylethylene glycol sulfate (MHPG-SO4) concentrations within the locus coeruleus, hypothalamus and hippocampus. No changes were detected in serotonin (5-HT) levels or turnover. Behavioral deficits following the stress were observed using measures of locomotion and of exploration in a novel open-field environment: stressed animals displayed much less spontaneous motor activity, hole-poking or frequency of standing on their hind legs than control animals. Animals receiving the tyrosine-enriched diet displayed neither the stress-induced depletion of NE nor the behavioral depression. These preventive effects of tyrosine were abolished by co-administration of valine, a large neutral amino acid that competes with tyrosine for transport across the blood-brain barrier. Since tyrosine alone, in animals not subjected to stress, did not change NE turnover nor the behaviors studied, our observations affirm that catecholaminergic neurons respond to the precursor amino acid only when they are physiologically active. Supplementary tyrosine may be useful therapeutically in people exposed chronically to stress.


Potential for interactions between the carboxy- and amino-termini of Rubisco activase subunits.
The subunit interactions of Rubisco activase were investigated using mutants containing an introduced Cys near the N- and/or C-terminus. Chemical cross-linking of the C-terminal and double insertion mutant produced subunit dimers and dimers plus high ordered oligomers, respectively. Fluorescence measurements with N,N'-dimethyl-N-(iodoacetyl)-N'-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)ethylenediamine showed that the environment around the introduced Cys near the C-terminus becomes more hydrophilic upon nucleotide binding. The Cys insertion mutants catalyzed Rubisco activation and ATP hydrolysis even when the subunits of the C-terminal or double insertion mutants were completely cross-linked. The results indicate that the termini of adjacent activase subunits are in close proximity and can be modified and even joined without affecting enzyme function.