Development and psychometric testing of the Antenatal Care Scale within the context of the Theory of Planned Behaviour.
To develop an instrument based on the Theory of Planned Behaviour (TPB) to determine the attitudes and intentions of women towards receiving antenatal care. This methodological study was carried out at health centres in Isparta, Turkey. 266 pregnant women who were able to communicate, did not have a systemic disease, and who volunteered to participate were included in this study. They were chosen by a random sampling method. A Likert-type scale composed of six subfactors and 26 items was used. Cronbach's α for the Antenatal Care Scale (ANCS) was 0.96, and values for the six subfactors were between 0.88 and 0.94. The ANCS was found to be a valid and reliable instrument to determine the attitudes and intentions of women towards receiving antenatal care.


Skin surface lipids of the mole Scalopus aquaticus.
Skin surface lipids of the mole Scalopus aquaticus were found to consist principally of squalene (70%), wax esters (15%), and sterol esters (5%), together with small amounts of triglycerides, free fatty acids, free fatty alcohols, and free sterols. Analysis of the fatty acids occurring free and as wax esters and sterol esters showed these to consist of approximately equal amounts of saturated and monounsaturated compounds. The saturated fatty acids consisted predominantly of odd-carbon anteiso and even-carbon straight-chain compounds, with minor amounts of even-carbon iso-branched chains. The unsaturated fatty acids had double bond positions that would have been produced by delta 9-desaturation of C14, C16 and C18 straight chain saturated precursors. Both the free and the esterified fatty alcohols had chain structures corresponding with those of the fatty acids but of somewhat greater average chain length. Discovery of a major proportion of squalene in the sebum of this animal extends the number of non-human species that have this characteristic to four, all of which inhabit a damp environment, suggesting that squalene conveys some biological advantage under these conditions.


Regulatory T cells in graft-versus-host disease.
Alloreactive T cells present in a bone marrow transplant are responsible for graft-vs-host disease, but their depletion is associated with impaired engraftment, immunosuppression, and loss of the graft-vs-leukemia effect. The subpopulation of CD4(+)CD25(+) immunoregulatory T cells was first identified based on its crucial role in the control of autoimmune processes, but they also play a role in alloreactive responses. Moreover, these cells could be used to develop innovative strategies in the field of transplantation and particularly to prevent graft-vs-host disease. Indeed, high numbers of CD4(+)CD25(+) immunoregulatory T cells can modulate graft-vs-host disease if administered at the same time as allogeneic hematopoietic stem cell transplantation in mice. This review discusses various important issues regarding the possible use of CD4(+)CD25(+) immunoregulatory T cells to modulate alloreactivity in hematopoietic stem cell transplantation.


Radiomics: extracting more information from medical images using advanced feature analysis.
Solid cancers are spatially and temporally heterogeneous. This limits the use of invasive biopsy based molecular assays but gives huge potential for medical imaging, which has the ability to capture intra-tumoural heterogeneity in a non-invasive way. During the past decades, medical imaging innovations with new hardware, new imaging agents and standardised protocols, allows the field to move towards quantitative imaging. Therefore, also the development of automated and reproducible analysis methodologies to extract more information from image-based features is a requirement. Radiomics--the high-throughput extraction of large amounts of image features from radiographic images--addresses this problem and is one of the approaches that hold great promises but need further validation in multi-centric settings and in the laboratory.


[Interdisciplinary treatment of a 3 1/2-year-old child with extensive ameloblastic fibro-odontoma. Case report and follow-up documentation over 21 1/2 years].
This report deals with a 3 1/2 year old patient with an ameloblastic fibro-odontoma of the frontal part and left corpus of the mandible. The tumor had become symptomatic 2 months prior to admittance by a local, painless swelling of the bone and the mobility of teeth. The initial findings and the progress of the disease led to the preliminary diagnosis of a malignant mesenchymal tumor. Its extent and aggressive growth prompted a continuity resection of the mandible and immediate reconstruction with a costal autograft. The definitive histological diagnosis was an ameloblastic fibro-odontoma. The patient was followed up over a period of 21 1/2 years. Further treatment included an iliac crest onlay graft, followed by autotransplantation of three third molars into both transplants. Two of the wisdom teeth had to be replaced by dental implants because of ankylosis and infra-occlusal positioning. The prosthetic rehabilitation was carried out by a bar attachment and a partial cover denture. This report supports the concept of the interdisciplinary treatment of patients with tumors that occur during the growth phase.


Selective synthesis of DC carbon arc-generated carbon nanotube and layered-graphene and the associated mechanism.
Herein we report how an anode is eroded and the eroded mass is deposited on the cathode surface at different arc currents ([Formula: see text]) in a DC carbon arc discharge using roughly oriented graphite (ROG) as electrodes. It was found that the nature of anode erosion critically depends on [Formula: see text] and has profound effects on the morphology of the as-synthesized cathode deposits (CDs), the conversion efficiency of the system to form the CDs and their compositions. By characterizing the as-synthesized CDs in their totality by transmission electron microscopy, Raman spectroscopy, and x-ray diffraction it was found that there exists a critical value of [Formula: see text] below which the arc remains constricted, and above which the arc becomes intense. It was further found that the system can selectively generate both carbon nanotubes (CNTs) and layered-graphene sheets (LGs) when the carbon arc runs in constricted and intense modes, respectively. By the suitable adjustment of [Formula: see text] it is possible to switchover between the aforementioned arc-modes. Based on the experimental results, a semi-empirical model encompassing the plausible effects of rapid and random movement of the anode spot on the used ROG anode surface was developed to provide new insights into the growth mechanism of arc-generated CNTs and LGs. The state-of-the-art presented in this paper could facilitate the carbon arc discharge route for the tailored synthesis of highly crystalline CNTs and LGs.


Creation of a COVID-19 Based Educational Curriculum: A Blueprint for Redesigning Surgical Education During Times of National Crisis.
To create a COVID-19 based educational curriculum for surgical residents. The COVID-19 pandemic has resulted in disruptions to operative volume and clinical education for surgery residents. This has placed a greater importance on didactic education. However, in the face of pandemic-related uncertainty, focusing on a traditional educational curriculum may be a challenge for surgical residents. A dedicated resident educational team was created. This team identified specific surgical resident needs, evaluated institutional resources, created a curriculum and timeline, determined a feasible implementation format, and assessed resident opinions on the impact of the curriculum via anonymous survey. A 1-month long COVID-19 based curriculum was developed, which covered (1) advanced critical care and resuscitation techniques pertinent to patients with COVID-19, (2) institutional physician experience in the COVID-units, (3) ethical dilemmas in resource management, (4) triaging of operative cases during the pandemic, and (5) published and ongoing COVID-19-related surgical research. In the postimplementation survey, a majority of residents reported that the curriculum helped improve their ability to take care of patients during the pandemic, provided an opportunity for questions, alleviated anxieties and concerns, and that they preferred the COVID-19 curriculum over traditional surgical topics. In the midst of national crisis and significant clinical disruption, real-time adjustments to surgical education can and should occur to address resident needs. The results of our study may serve as a blueprint for implementing rapid change to resident education in the future.


Clinical characteristics and the associated risk factors of the development of bilateral breast cancers: A case-control study.
The clinical impacts of bilateralism on prognosis and clinical decision-making remain contradictory particularly in areas with low incidence and delayed diagnosis of primary breast cancer. Identification of women at risk of bilateral breast cancer is required to improve patient management and to design the appropriate surveillance. A total of 1083 women were enrolled and analyzed for the presence of synchronous and metachronous bilateral breast cancer as cases and unilateral breast cancer as controls during the median follow-up of 4.8 years. The incidence of bilateral breast cancer was 7.5% (81 of 1083). In comparison with unilateral breast cancers, bilateral cases were significantly diagnosed in younger women (P = 0.037, mean age was 35.6 years) who had a larger tumor size (P = 0.012, mean tumor size was 8 cm in diameter). Histological type of lobular cancer was identified as one of the risk factors for the development of contralateral breast cancer (OR 5.564, 95% CI: 3.219-9.620) and synchronous bilateral breast cancer (OR 2.561, 95% CI: 1.182-5.550). Bilateral breast cancer had significantly shorter progression-free survival (Mean survival was 26.6 vs 52.5 months for bilateral and unilateral breast cancers, respectively; P = 0.001) and shorter time to develop distant metastasis (Mean survival was 41.7 vs 104 months for bilateral and unilateral breast cancers, respectively; P = 0.001). Patients with first primary breast tumors with lobular histological type and advanced stages were observed to have higher risks for the development of contralateral breast cancers.


Central cholinergic activation induces greater thermoregulatory and cardiovascular responses in spontaneously hypertensive than in normotensive rats.
There is evidence that central cholinergic stimulation increases heat dissipation in normotensive rats besides causing changes on the cardiovascular system via modulation of baroreceptors activity. However, the contribution of the central cholinergic system on thermoregulatory responses and its relationship with cardiovascular adjustments in spontaneously hypertensive rats (SHRs), an animal model of reduced baroreceptor sensitivity and thermoregulatory deficit, has not been completely clarified. Therefore, the aim of this study was to verify the involvement of the central cholinergic system in cardiovascular and thermoregulatory adjustments in SHRs. Male Wistar rats (n = 17) and SHRs (n = 17) were implanted with an intracerebroventricular cannula for injections of 2 µL of physostigmine (phy) or saline solution. Tail temperature (Ttail), internal body temperature (Tint), systolic arterial pressure (SAP), heart rate (HR) and metabolic rate were registered during 60 min while the animals remained at rest after randomly receiving the injections. The variability of the SAP and the HR was estimated by the fast Fourier transform. Phy treatment began a succession of cardiovascular and thermoregulatory responses that resulted in increased SAP, reduced HR and increased Ttail in both Wistar and SHRs groups. The magnitude of these effects seems to be more intense in SHRs, since the improvement of heat dissipation reflected in Tint. Taken together, these results provide evidence that hypertensive rats present greater cardiovascular and thermoregulatory responses than normotensive rats after central cholinergic stimulation.


Hypercalcemia and elevated 1,25(OH)2D3 levels in a dialysis patient with disseminated tuberculosis.
A 37-year-old diabetic patient with end-stage renal disease on maintenance dialysis developed widely disseminated tuberculosis. Tuberculosis was associated with hypercalcemia, inappropriately elevated serum levels of 1,25(OH)2D3, and consistently suppressed serum levels of iPTH. This case provides additional evidence that in granulomatous diseases extrarenal synthesis of 1,25(OH)2D3 may occur.


The biochemical characteristics of Campylobacter-like organisms from cattle and pigs.
Examination of catalase-positive Campylobacter-like organisms from cattle and pig abortions, indicated the existence of two distinct biochemical groups. The group 1 strains, predominantly of intestinal origin, were identified as C fetus subspecies intestinalis whereas the group 2 strains appeared similar but not identical to C fetus subspecies venerealis. This second group of organisms was recovered from fetal and placental tissue of animals which aborted, however, the majority of strains were isolated only at 30 degrees C in media not generally employed for Campylobacter isolation. All of the strains from group 2 became aerotolerant on subculture.


Patient safety education - a description and evaluation of an international, interdisciplinary e-learning programme.
Patient safety is a priority within healthcare across the globe. Delivering safer healthcare demands a system wide approach and educators have a responsibility to play a full role. This article describes how e-learning can be a means of engaging and educating an international group of critical care professionals studying at Masters level. Using online tools such as blogs, wikis and discussion boards students are introduced to quality and safety subjects and tools to help them improve care at a local level. Working together as a collaborative of different professionals has engaged the student group helping them understand their role in reducing harm and has resulted in improvements to care.


Late mortality after severe traumatic brain injury in New South Wales: a multicentre study.
To determine the long-term mortality pattern of adults with severe traumatic brain injury (TBI), and to identify the risk factors associated with death in this group. Inception cohort study of 2545 adults consecutively discharged from one of three metropolitan tertiary, post-acute inpatient rehabilitation services of the New South Wales Brain Injury Rehabilitation Program from 1 January 1990 to 1 October 2007 after inpatient rehabilitation for primary TBI. Survival status at 1 October 2009. 258 deaths were recorded in this sample, yielding a standardised mortality ratio of 3.19 (95% CI, 2.80-3.60). Risk of death remained elevated above societal norms for at least 8 years after discharge from rehabilitation. Mortality risk was increased by: functional dependence at discharge; age at injury; pre-injury drug and alcohol misuse; pre-injury epilepsy; and discharge to an aged care facility. The risk of death from external causes, and respiratory system and nervous system disorders was six to seven times higher, and the risk of death from disorders of the digestive system, and mental and behavioural disorders was five times higher in adults with severe TBI than in the general population. People who survive to discharge from inpatient rehabilitation following a severe TBI were found to have a sustained increase in risk of death for eight years post discharge. Various demographic and injury-related variables selectively increase mortality risk and may be modifiable in order to reduce the observed increase in mortality.


Retroperitoneal seminoma presenting with inferior vena caval obstruction.
A retroperitoneal seminoma in the presence of clinically normal testes can present a considerable diagnostic problem and therapeutic dilemma. We report on a patient with low back pain and inferior vena caval obstruction in whom no primary neoplasm could be detected by surgical exploration of the testes.


Hypoglossal nerve trunk stimulation: electromyography findings during drug-induced sleep endoscopy: a case report.
Literature has demonstrated hypoglossal nerve stimulation to be a safe and effective treatment for patients with obstructive sleep apnea nonadherent to positive airway pressure therapy. However, the recommended criteria for patient selection are still unable to identify all the unresponsive patients, highlighting the need for improved understanding about hypoglossal nerve stimulation for obstructive sleep apnea. A 48-year-old Caucasian male patient with obstructive sleep apnea had been successfully treated with electrical stimulation of the hypoglossal nerve trunk, documented by level 1 polysomnography data. However, due to snoring complaints, he underwent postoperation drug-induced sleep endoscopy for evaluation of electrode activation during upper airway collapse, aiming to improve electrostimulation parameters. Concurrent surface electromyography of the suprahyoid muscles and masseter was obtained. Activation of electrodes 2, 3, and 6 promoted upper airway opening most strongly at the velopharynx and tongue base during drug-induced sleep endoscopy. The same channels also significantly increased the electrical activity on suprahyoid muscles bilaterally, but predominantly on the stimulated side (right). The masseters also presented a considerable asymmetry in electrical potential on the right side (> 55%). Beyond the genioglossus muscle, our findings demonstrate recruitment of other muscles during hypoglossal nerve stimulation, which may be attributed to the electrical stimulation of the nerve trunk. This data provides new insights on how stimulation of the hypoglossal nerve trunk may contribute to obstructive sleep apnea treatment.


Patterning stem cell differentiation.
Regulation of cell differentiation and assembly remains a fundamental question in developmental biology. Now, a report from the Chen laboratory (Ruiz and Chen, 2008) describes an approach that represents a major step toward a more profound understanding of the geometric-force control of stem cell differentiation.


ABO identical and washed blood transfusions as candidate strategies to reduce early mortality in acute promyelocytic leukemia.
Despite dramatically improved long term outcomes seen with all-trans retinoic acid therapy, and now arsenic trioxide, in acute promyelocytic leukemia (APL), early mortality remains a substantial challenge. Recent data from a single center study and the Surveillance, Epidemiology and End Results (SEER) registry report 30day mortality rates of 26% (n=18 of 70) and 17% (n=238 of 1400), respectively. Early deaths are predominately due to hemorrhage. Patients with APL invariably have abnormal laboratory hemostasis tests. The standard of practice is to prophylactically transfuse platelets, plasma and cryoprecipitate to mitigate abnormal platelet counts, PT/PTT and fibrinogen levels. Standard blood bank practice is to transfuse platelets, plasma and cryoprecipitate largely without regard to ABO blood group (platelets, cryoprecipitate), and, in some centers, transfusing ABO non-identical universal donor group AB plasma. Evidence from observational studies suggests that use of ABO non-identical blood components may be associated with increased bleeding. We hypothesized that use of ABO identical blood components and saline washed transfusions (red cells and platelets) would be associated with reduced early mortality in APL by avoidance of transfusion induced hemostatic dysfunction. This is a single center cohort study of APL patients treated in an 800 bed university community and referral hospital. Novel approaches to transfusion support, based upon randomized trials, include implementation of ABO identical platelet transfusions for all patients with acute leukemia in 1990, use of only ABO identical cryoprecipitate in 2005, and washed transfusions of red cells and platelets for all patients with acute leukemia <50years of age beginning in 2006. Plasma transfusion has always been ABO identical. Two comparison populations were recent literature reports and the New York State Cancer Registry. We characterized 30 day mortality in APL patients seen in our institution since 2000 as a convenience sample comparable to literature reports, beginning approxcimately when ATRA therapy became uniform for induction therapy. Only patients receiving their induction therapy in our hospital were included. Of 41 patients there were 2 early (30 day) deaths (5%; a 71-81% reduction from expected). Early mortality at 100 days was 7% (n=3). The 30 day mortality in the younger cohort <50years of age (n=16) receiving washed transfusions was 0%. Restricting the analysis to patients treated since 2006 (ABO identical transfusions, mostly washed) (n=27; mean age 43 years; median 41 years; range 12-79), the early mortality rate at 30days was 3.7%. Long-term survival (5 years) of our APL patients was similar to New York State Cancer Registry and literature reports (80-83%). APL patients supported with transfusion regimens including ABO identical blood components, with or without washing, experienced early mortality at 30 days that was strikingly improved (71% to 86% lower) compared with that reported in the recent literature (3.7% to 5% vs. 17% to 26%). If these observed low rates of early mortality are related to transfusion practices, avoidance of ABO immune complex formation, and subsequent interference with hemostasis, is a plausible contributing mechanism. These favorable results provide a rationale for randomized trials of relatively simple and inexpensive approaches to reducing early hemorrhagic mortality in APL: use of ABO identical transfusions and washing to remove supernatant plasma.


Disturbance of oxidation/antioxidant status and histopathological damage in tsinling lenok trout under acute thermal stress.
The tsinling lenok trout (Brachymystax Lenok tsinlingensis) is a typical land-locked cold salmon. In this study, through the acute high temperature stress (16, 24, and 26°C), samples were taken at multiple temperature points to analyze the dynamic changes of serum non-specific immune indexes and histopathological changes of tissues of tsinling lenok trout. The histopathological investigation of different studied tissues revealed an increase of histological lesions' frequency and severity with increasing water temperature. The activity of T-SOD, GSH-Px, CAT, ACP, and LZM and MDA concentration are all impacted by high temperature stress. The activities of T-SOD, GSH-Px, and ACP are significantly lower in temperatures higher than 16°C (P<0.05). However, with the increase of water temperature, MDA content increased significantly. The activities of CAT and LZM were the highest at 24°C, which were significantly higher than those at 26°C (P<0.05). The above results indicate that 24°C is a "critical high temperature point" for tsinling lenok trout under heat stress, and this temperature point may be the critical point for tsinling lenok trout to enter "damaged" from adaptive adjustment. Our results can provide a theoretical basis for the development of genetic breeding, improvement, and control measures of heat stress in tsinling lenok trout in the future.


Immunocytochemical demonstration of the transport of myelin proteolipids through the Golgi apparatus.
Purified antibodies directed against myelin proteolipids were isolated by affinity chromatography of whole serum obtained from rabbits inoculated with myelin. These antibodies were specific for light, medium and dark oligodendrocytes. Astrocytes, neurons and their processes were not reactive. Immunocytochemical investigations showed that the membranes of the Golgi complex are highly labeled by these antibodies. Diffuse cytoplasmic labeling was only observed on the light and medium oligodendrocytes and was absent from the dark types. Vesicles possessing a punctate staining were detected in the vicinity of the Golgi complex and the oligodendroglial membrane. A discontinuous labeling of the plasmalemma appears to be characteristic of the actively myelinating light and medium oligodendrocytes. In compact myelin sheaths positive immunostaining was only detected at the dense line. The immunocytochemical localization of the myelin proteolipids in the oligodendrocytes is in accordance with previously published biochemical data.


Something's gotta give at the centromeric chromatin foundation of the kinetochore.
Structures of the reconstituted human inner kinetochore complex by Pesenti et al. (2022) and Yatskevich et al. (2022) raise the question of whether it is the CENP-A nucleosome or the CCAN complex itself that provides the foundation for kinetochore assembly.


Metabolic activity of cultured rat brainstem, hippocampal and spinal cord slices.
The use of cultured brain slices has become an accepted technique for the ex vivo analysis of neural mechanisms, yet the viability of this preparation is not routinely measured. The tetrazolium dye 3-(4, 5-dimethlythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) is reduced by active mitochondria to an insoluble purple precipitate which accumulates within living cells and is easily visualized with bright field or phase contrast microscopy. In this study, the MTT assay was used to assess the viability of cultured brainstem, hippocampal and spinal cord slices (150-300 micrometer) from 0 to 22 day-old neonatal rats at post-explant time points ranging from 2 to 29 days. After 2 weeks, 180-300 micrometer cultured slices from 4-13 day old rats remained 90-100% viable. Those from 0-1 day old rats had similar viability but displayed peripheral tissue outgrowth. Slices from older 18-22 day rats were no longer viable after 10-14 days. After 4 weeks, the thicker (300 micrometer) slices of hippocampus and spinal cord retained 75-89% viability, in contrast to the 50-74% viability of the brainstem. Thinner brainstem and hippocampal slices (150-220 micrometer) slices were less than 50% viable at 4 weeks. Morphologic characteristics of the brain regions gradually degenerated over the 4-week culture period. Slice viability was markedly influenced by tissue thickness, donor age and brain region. Use of the MTT assay provides an inexpensive and expeditious means to assess a significant functional parameter of regional slice viability under variable conditions and enhances the feasibility of this preparation for functional studies, such as those concerned with genetic and protein expression within circumscribed areas of the brain.


Efficacy of high-dose methylprednisolone as a first-line therapy in adult patients with idiopathic thrombocytopenic purpura.
Fifty-seven adult patients with idiopathic thrombocytopenic purpura (ITP) were treated with either conventional-dose prednisolone (CDP) (1 mg/kg/d, 36 patients) or high-dose methylprednisolone (HDP) (30 mg/kg/d, 21 patients), as first-line treatment. Patients in the HDP arm responded more rapidly (4.7 v 8.4 d), with a higher response rate (80% v 52.7%), and without severe side-effects. One quarter of the patients (3/12) who were non-responsive to CDP achieved complete remission when they were treated with HDP. The findings suggest that HDP may be a more effective first-line treatment than CDP for adult ITP, and it may also be preferred for life-threatening cases of ITP. However, these results must be confirmed by a randomized study prior to any change in the current practice of employing CDP as first-line treatment for adult ITP.


Ursodeoxycholic acid stabilizes the bile salt export pump in the apical membrane in MDCK II cells.
Ursodeoxycholic acid (UDCA) partly exerts choleretic effects by modifying the function of the bile salt export pump (Bsep, ABCB11). UDCA induces insertion of Bsep into the canalicular membrane of hepatocytes; however, underlying mechanisms remain unknown. We aimed to elucidate molecular mechanisms behind UDCA-induced Bsep activation. We established MDCK II cells stably expressing both Bsep and Na(+)-taurocholate cotransporting polypeptide, and investigated the effect of UDCA on activity and protein expression of Bsep using these cells. We performed inhibitor study to know the molecules involved in UDCA-induced Bsep activation, and also tested the influence of UDCA on Bsep having a disease-associated mutation. UDCA activated Bsep in a dose-dependent manner. UDCA did not affect Bsep protein expression in whole cell lysates but increased its apical surface expression by extending the half-life from 2.4 to 5.0 h. This effect was specific to Bsep because UDCA did not affect other apical and basolateral proteins, and was independent of protein kinase A, adenylate cyclase, p38(MAPK), phosphatidylinositide 3-kinase, Ca(2+), and microtubules. NorUDCA activated Bsep similar to UDCA; however, cholic acid, taurocholic acid, and tauroUDCA had no effect. UDCA significantly increased the activity of Bsep with a benign recurrent intrahepatic cholestasis 2 mutation (A570T) but did not affect Bsep with a progressive familial intrahepatic cholestasis 2 mutation (G982R or D482G). We demonstrated that UDCA stabilizes Bsep protein in the apical membrane and increases its activity in MDCK II cells, presumably by retarding the endocytotic process.


Intermediate results of the anatomic repair for congenitally corrected transposition.
Anatomic repair of congenitally corrected transposition of the great arteries has several advantages over the traditional approach but lacks long-term evaluation. The data on 12 patients who had the procedure between January 1989 and June 2000 were retrospectively reviewed. Associated lesions included ventricular septal defect in 12 patients, pulmonary stenosis in 10 patients, and moderate to severe tricuspid valve regurgitation in 4 patients. Mean age at operation was 9+/-3.6 months. All patients had venous switch Mustard procedure. Tunneling of the morphologic left ventricle through the ventricular septal defect to the aorta with insertion of right ventricular to pulmonary artery conduit was performed in 10 patients, and arterial switch operation in 2. Concomitant tricuspid valvuloplasty was done in 2 patients and ventricular septal defect enlargement in 1. There was one hospital death (9%) in the patient who needed ventricular septal defect enlargement. Complications included atrioventricular block requiring pacemaker insertion in 1 patient (9%) and superior vena caval obstruction in 1 patient (9%). Follow-up is available on all patients 0.5 to 10 years (mean, 7.6+/-3.1 years). All patients are asymptomatic. Exercise test results on the three oldest patients were normal. Bradytachyarrhythmias developed in 4 patients (36%). Right ventricular to pulmonary artery conduit replacement was needed in 5 patients 2.2 to 7.1 years (mean 5.2+/-3.6 years) postoperatively. Mild to moderate tricuspid valve regurgitation persisted in 2 patients. Systemic left ventricular fractional shortening was 36% to 47% (mean, 39%+/-4.6%), and ejection fraction was 49% to 70% (mean, 60.8%+/-7.9%). The double switch operation can be performed safely with minimal intermediate and long-term complications.


Analysis of factors that determine the diagnostic yield of temporal artery biopsy.
To analyse the diagnostic yield of temporal artery biopsy in the diagnosis of giant cell arteritis, and to correlate these results with the clinical and laboratory features which indicate it, in an attempt to increase the efficiency of this technique and try to "save biopsies". A retrospective cohort study including suspected giant cell arteritis cases in which a temporal artery biopsy was performed. The data recorded included demographic, clinical and laboratory information. A total of 38 patients were analysed. The biopsy was positive in 68.42% of cases. Multivariate analysis revealed visual symptoms and a high C-reactive protein as parameters with a high diagnostic efficiency. Our study supports the fact that temporal artery biopsy should be undertaken when there is strong clinical suspicion. Visual symptoms and high C-reactive protein are considered as a high efficiency indicators to biopsy.


[Effectiveness of a patient-centered psychosomatic consultation service. Report of a catamnestic study].
After a short review of the latest scientific publications on psychosomatic consultation activity the results of an empirical study of the consultant service in the Department of Psychotherapy and Psychosomatic Medicine at the Frankfurt University Medical Center are presented. Patient documentations and data from a retrospective investigation were analysed in order to trace the effectivity of psychosomatic consultation activities. To document the various dimensions of the consultative process and their interdependence different groups of patients were derived by means of cluster analysis. The results are in many aspects encouraging for psychosomatic consultative practice, as they show that even few consultations can have an important influence on the patient's further development.


Enhanced bodily states of fear facilitates bias perception of fearful faces.
We investigated whether enhanced interoceptive bodily states of fear would facilitate recognition of the fearful faces. Participants performed an emotional judgment task after a bodily imagery task inside a functional magnetic resonance imaging scanner. In the bodily imagery task, participants were instructed to imagine feeling the bodily sensations of two specific somatotopic patterns: a fear-associated bodily sensation (FBS) or a disgust-associated bodily sensation (DBS). They were shown faces expressing various levels of fearfulness and disgust and instructed to classify the facial expression as fear or disgust. We found a stronger bias favoring the "fearful face" under the congruent FBS condition than under the incongruent DBS condition. The brain response to fearful versus intermediate faces increased in the fronto-insular-temporal network under the FBS condition, but not the DBS condition. The fearful face elicited activity in the anterior cingulate cortex and extrastriate body area under the FBS condition relative to the DBS condition. Furthermore, functional connectivity between the anterior cingulate cortex/extrastriate body area and the fronto-insular-temporal network was modulated according to the specific bodily sensation. Our findings suggest that somatotopic patterns of bodily sensation provide informative access to the collective visceral state in the fear processing via the fronto-insular-temporal network.


Carpal tunnel syndrome in postmenopausal women.
Hormonal changes that accompany menopause have a significant impact on the nervous and other physiological systems. Our objective was to evaluate the relationship between carpal tunnel syndrome (CTS) and the clinical features of menopause in postmenopausal women, in comparison to age-matched healthy controls. Overall, 6230 women were seen during the study period. Of these, 5587 were not eligible because they were premenopausal or perimenopausal. 537 women did not meet the criteria used in the study for a diagnosis of idiopathic CTS and were excluded. Finally, one hundred and six patients with CTS and 115 controls were examined. The presence of CTS was confirmed both clinically and electrophysiologically. Socio-demographic variables and reproductive histories were evaluated via a structured interview. In comparison to healthy controls, patients with CTS showed a significantly greater number of pregnancies and an earlier age at menopause. Regarding the type of menopause, patients and controls showed similar frequencies for natural versus surgical menopause. The frequency of natural menopause was significantly higher than that of surgical menopause in both groups. Our results suggest that age at menopause may be a significant factor in the development of CTS. Pregnancy-related hormonal changes may have long-term effects that increase the incidence of CTS in postmenopausal women.


Serum total and free testosterone level of Japanese men: a population-based study.
There has never been a large scale population-based study of serum levels of total testosterone (TT) and free testosterone (FT) in Japanese men. We determined serum levels of TT and FT of 1120 Japanese men aged 40-79 years using radioimmunoassay (RIA), as a part of a population-based longitudinal study of aging. Of these, sex hormone binding protein (SHBG) was also measured by RIA in 471 men. For the latter group, the calculated free testosterone (cFT) was determined by a formula using serum level of albumin, TT and SHBG. The mean +/- 2 SD of TT, FT and cFT were 513 +/- 326 ng/dL (187-839 ng/dL), 13.2 +/- 7.8) pg/mL (5.4-21.0 pg/mL) and 77.0 +/- 43.4 pg/mL (33.6-120.4 pg/mL), respectively. While TT did not relate to age, FT and cFT decreased with age. FT in the 40-49 years age group was 15.1 +/- 8.4 pg/mL (6.7-23.5 pg/mL), in the 50-59 years age group was 13.9 +/- 6.8 pg/mL (7.1-20.7 pg/mL), in the 60-69 years age group was 12.0 +/- 6.6 pg/mL (5.4-18.6 pg/mL) and in the 70-79 years age group was 11.5 +/- 7.0 pg/mL (4.5-18.5 pg/mL). FT significantly correlated with cFT (Spearman's r = 0.803). The correspondence rates were 92.3% at the mean -1 SD and 98.7% at the mean -2 SD level. We determined the mean and standard deviation of TT, FT and cFT in Japanese men aged 40 years or older. It is supposed that FT determined by RIA would be useful for diagnosing partial androgen deficiency of aging males.


Endoscopic laser-assisted diverticulotomy versus open surgical approach in the treatment of Zenker's diverticulum.
This study aimed to evaluate the results of endoscopic laser-assisted diverticulotomy and the transcervical approach in treating Zenker's diverticulum. Retrospective clinical study. Results of 155 cases after endoscopic laser-assisted diverticulotomy and the transcervical approach were retrospectively compared. Primary treatment consisted of endoscopic laser-assisted diverticulotomy in 65.2%, and 34.8% were treated by a transcervical approach. Average follow-up time was 61.8 months. Surgical time, duration of hospitalization, and occurrence of minor complications were significantly lower after endoscopic approach. Recurrence rate showed a statistically significant difference in favor of open approach. Including the recurrences, 38.7% could be cured only by transcervical techniques. Patient perception of success was found to be similar for the compared treatment modalities. Endoscopic approach proved to be the treatment of first choice. However, the fact that open techniques were necessary in nearly 40% of our cases suggests that this operative technique retains a substantial role in treatment of this disease.


Comparison of pelvic complex kinematics during treadmill and overground walking.
To determine if there are changes in temporal gait parameters with a focus on pelvis when comparing overground and treadmill ambulation, and to assess the effect of sex. An observational study employing motion analysis techniques to evaluate pelvic movement during gait. University biomechanics laboratory. Men (n=8; 22.5±3.0 y) and women (n=6; 23.8±4.1 y). Not applicable. Cadence, stride time, stance phase percent, and pelvic tilt, obliquity, and rotation parameters throughout the gait cycle were assessed during overground and treadmill walking. Kinematic data were recorded using a passive full body marker based motion analysis system. While an independent sample t test was used to determine if differences in walking speed were evident between sexes, a 2-way, repeated-measures analysis of variance was performed to examine the effect of walking mode and sex on each dependent variable. Significant differences (P<.05) between overground and treadmill walking for the temporal parameters analyzed were evident for both sexes. A lower pelvic obliquity motion for treadmill walking when compared with overground walking was evident for both sexes, and the pelvic rotation movement pattern showed the greatest difference between walking modes. The majority of the significant differences between sexes were of a magnitude greater than the differences between overground and treadmill walking. The differences in temporal and angular kinematics identified in the present study should be considered when treadmills are used in a rehabilitation program.


Regulation of the RNA polymerase II pre-initiation complex by its associated coactivators.
The RNA polymerase II (Pol II) pre-initiation complex (PIC) is a critical node in eukaryotic transcription regulation, and its formation is the major rate-limiting step in transcriptional activation. Diverse cellular signals borne by transcriptional activators converge on this large, multiprotein assembly and are transduced via intermediary factors termed coactivators. Cryogenic electron microscopy, multi-omics and single-molecule approaches have recently offered unprecedented insights into both the structure and cellular functions of the PIC and two key PIC-associated coactivators, Mediator and TFIID. Here, we review advances in our understanding of how Mediator and TFIID interact with activators and affect PIC formation and function. We also discuss how their functions are influenced by their chromatin environment and selected cofactors. We consider how, through its multifarious interactions and functionalities, a Mediator-containing and TFIID-containing PIC can yield an integrated signal processing system with the flexibility to determine the unique temporal and spatial expression pattern of a given gene.


Suppressed Akt/GSK-3β/β-catenin signaling contributes to excessive adipogenesis of fibro-adipogenic progenitors after rotator cuff tears.
Muscular fatty infiltration is a common and troublesome pathology after rotator cuff tears (RCT), which mainly derives from fibro-adipogenic progenitors (FAPs). Compared to the RCT, fatty infiltration is not so severe in Achilles tendon tears (ATT). The knowledge of why fatty infiltration is more likely to occur after RCT is limited. In this study, more severe fatty infiltration was verified in supraspinatus than gastrocnemius muscles after tendon injury. Additionally, we revealed higher adipogenic differentiation ability of RCT-FAPs in vitro. Activation of Akt significantly stimulated GSK-3β/β-catenin signaling and thus decreased PPARγ expression and adipogenesis of RCT-FAPs, while the inhibition effect was attenuated by β-catenin inhibitor. Furthermore, Wnt signaling activator BML-284 limited adipogenesis of RCT-FAPs, alleviated muscular fatty infiltration, and improved parameters in gait analysis and treadmill test for RCT model. In conclusion, our study demonstrated that suppressed Akt/GSK-3β/β-catenin signaling increased PPARγ expression and thus contributed to excessive adipogenesis in RCT-FAPs. Modulation of Akt/GSK-3β/β-catenin signaling ameliorated excessive fatty infiltration of rotator cuff muscles and improved shoulder function after RCT.


High-dose preoperative fractionated radiotherapy does not affect the patency and healing of ePTFE vascular prosthesis after replacement of canine abdominal aorta and inferior vena cava.
Fractionated radiotherapy allows for the safe administration of larger doses without the development of immediate or late toxicity. The influence of preoperative fractionated radiotherapy on neointima formation for expanded polytetrafluoroethylene (ePTFE) graft has not been determined. Twenty mongrel dogs were randomly divided into radiotherapy group (a total dose of 35 Gy) or control group (no radiation). The infrarenal abdominal aorta and inferior vena cava were replaced by ePTFE grafts at 3 months after irradiation in the radiotherapy group. Grafts were explanted at 4 weeks after surgery. Histopathological techniques were undertaken to evaluate graft neointima formation. The control group was managed the same as the radiotherapy group except for not receiving irradiation. Four grafts implanted into inferior vena cava in the irradiated group and three in the control group were found to be completely occluded. None of the grafts implanted into abdominal aorta were obstructed. In the case of the inferior vena cava graft, the thickness of the graft neointima did not differ significantly between the irradiated and control groups. However, for the abdominal aorta graft, the neointima thickness in the irradiated groups was significantly thinner than that in the control group. Preoperative fractionated radiotherapy affects vascular healing via suppressing the development of neointima formation in the abdominal aorta graft.


Labyrinthine lesions in presumed inner ear hemorrhage-related sudden deafness.
Inner ear hemorrhage (IEH) is a rare cause of sudden sensorineural hearing loss (SSNHL). This study aimed to evaluate the lesional patterns in patients with presumed IEH from morphological and functional aspects. Seventeen patients with SSNHL and presumed IEH who completed audio-vestibular tests were included. The main outcome measures included clinical characteristics, radiology, and functional test results. The morphological findings and functional tests revealed differences in locations and lesional spectrums. The magnetic resonance imaging (MRI) hyperintensity was likely to involve the vestibule (88.2%), the cochlea (76.5%), and the posterior and lateral semicircular canals (76.5% and 70.6%, respectively). Furthermore, 70.6% of cases showed abnormality in the entire labyrinth, and abnormalities in the vestibule/semicircular canals were observed in 17.6% of cases. Meanwhile, dysfunction was sequentially detected in the cochlea (100%), semicircular canals (94.1%), and vestibule (70.6%); 64.7% of cases showed combined deficit in the entire labyrinth, and 29.4% of cases showed combined deficit in the cochlea/semicircular canals. Although lesions in the labyrinth were frequently detected, the results of the radiological and functional tests did not always match and significantly differed in either cochlear or superior semicircular canal damage detection (p < 0.05 each). In this cohort, IEH preferentially caused sudden audio-vestibular impairment, which was well demonstrated by a combination of MRI and functional tests. The specific lesional configurations revealed in this study may suggest a possible pathomechanism that could be further explored as a therapeutic target.


Cognitive dysfunction in severe chronic obstructive pulmonary disease (COPD) with or without Long-Term Oxygen Therapy (LTOT).
Chronic Obstructive Pulmonary Disease (COPD) is a progressive respiratory condition which can lead to comorbidities of variable severity, cognitive dysfunction included. The role of supplemental oxygen in preventing COPD-induced cognitive deterioration is still debated, but only episodically investigated. The aim of this study was to compare the cognitive pattern of hypoxemic COPD subjects treated with long-term oxygen (LTOT) to that of patients of comparable severity assuming oxygen on irregular basis, and to normal reference values. Lung function, arterial blood gases, health status, and cognitive function measured by means of four psychometric tests focusing different domains of cognition (such as: MMSE, Clock test; TMT-A; TMT-B) were assessed in 146 well matched hypoxemic COPD patients (males n = 96, 66%; mean age = 70.5 ± 12.9). Seventy-three patients were assuming long-term oxygen (LTOT), while the remaining seventy-three were only using oxygen as needed (AN). Regarding statistics, t test and ANOVA (Duncan test) were used to analyze data, assuming a p < 0.05 as the lowest limit of significance. Even though all COPD patients showed a poorer psychometric profile vs corresponding normal reference values, LTOT patients showed a lower prevalence of severe deterioration in cognition. Also the extent of impairment was significantly lower in these patients when assessed by TMT-A and TMT-B (p < 0.012 and 0.001, respectively), but not when measured by MMSE and Clock test (both p = ns). Several domains of cognition are variably affected by persistent hypoxemia in COPD patients. A panel of psychometric tools is needed for identifying the pattern of cognitive dysfunctions in these patients. Memory and attention (functions assessed by MMSE and Clock test) are only mildly-moderately affected, while visual processing, reproduction of numeric sequences, cognition flexibility, and shifting capacity (functions assessed by TMT-A and TMT-B) are much more deteriorated (p < 0.012 and p < 0.001, respectively). Only LTOT allows to preserve significantly (p < 0.022) cognitive functions from the COPD-induced deterioration. This assumption is of strategic value for COPD patients who are prescribed long-term oxygen because they frequently are not aware of the cognitive risks related to their condition.


Preclinical pharmacology of the antitumor agent O-6-methylguanine in CDF1 mice.
O-6-methylguanine (O6-mG), a guanine analog recently shown to be a potent inhibitor of alkylguanine-DNA alkyltransferase, has been found to potentiate the antitumor activity of nitrosoureas, in particular, carmustine (BCNU), in resistant cell lines (HT-29 mer+) and is targeted for development as a modulating agent with chloroethyl nitrosoureas. A high-performance liquid chromatography (HPLC) assay of O6-mG in plasma has been developed using a microC18 reverse-phase column. O6-mG and the internal standard deoxyguanosine (dGuo) were eluted with a linear gradient of from 15% to 35% methanol in 0.5 M ammonium acetate (pH 6.5) at a flow rate of 1 ml/min. The assay was linear over a 4-log concentration range with a detection limit of 0.1 microgram/ml. The within-run and between-run coefficients of variation (CV) were found to be 8.1% and 9.3%, respectively. The pharmacokinetics (PK) of O6-mG were investigated in healthy CDF1 mice following separate i.v. and i.p. administrations. At 20 mg/kg i.v., plasma O6-mG gave a biexponential profile with a terminal half-life (t1/2) of 24 min and a total clearance (CLT) of 23.7 ml min-1 kg-1. Higher doses (40-80 mg/kg) revealed a fluctuating third phase, probably due to enterohepatic cycling. Dose-dependent kinetics as measured by CLT and area under the plasma-concentration curve (AUC) values were also seen. Following i.p. dosing, O6-mG was completely absorbed and available to the circulation. No acute toxicity was observed in the animals, except for mild sedation, a possible side effect of the 10% ethanol used in the formulation. Studies on the cellular metabolism of highly purified [3H]-O6-mG have shown that the compound is not anabolized by a human lymphoblastoid cell line (CEM). Biochemistry studies have shown that the parent molecule is inactivating the alkylguanine-DNA alkyltransferase (AGT), thus exerting its pharmacological effect.


A fluid-structure interaction study using patient-specific ruptured and unruptured aneurysm: the effect of aneurysm morphology, hypertension and elasticity.
Fluid-structure interaction (FSI) simulations using five patient-specific aneurysm geometries are carried out to investigate the difference between ruptured and unruptured aneurysms. Two different blood pressure conditions (normal and hypertension, for all cases), and two different values of elastic modulus (1 and 2MPa, for two cases) are tested. Ruptured aneurysms (RA) generally displayed larger displacement at the dome, lower area-average WSS and higher von Mises stress than unruptured aneurysms (URA) regardless of elasticity or blood pressure condition. RAs had a longitudinal expansion whereas URAs had a radial expansion, which was the key difference between the two types. The difference in expansion pattern may be one of the keys to explaining aneurysm rupture, and further analysis is required in the future to confirm this theory.


The Marburg Museum Anatomicum and its unusual gynecological specimens: A brief history and ethical contextualisation.
The Marburg Museum Anatomicum displays a number of unique specimens related to obstetric problems. An ethically intensely disputed example is the bisected body of a pregnant woman and her fetus. Current information stemming from previous publications relates it to a fictional young woman who, who, having got pregnant by a student, committed suicide. This narrative was derived from a novel by the author Walter Bloem (1868-1951), orally transmitted without further proof of reliability. The present study attempts to uncover the true background beyond this narrative and to clarify the acquisition of the body by the anatomical collection and its personal background. Archival material as well as contemporary publications of professors of obstetrics and of anatomy along with data derived from civil and ecclesiastic registry offices were evaluated and compared with observations on the specimen. Comparison of data derived from the fictional description and observations on the specimen showed significant differences, excluding the narrative as a reliable source. Closer examination of the scientific output of former chairs of obstetrics showed that Professor Wilhelm Zangemeister (1871-1930), head of the clinics of gynecology and obstetrics between 1910 and 1925, published several studies on the clinical significance of narrow pelvis during delivery. In his textbook of obstetrics, published in 1927, he showed an illustration of a frozen section of a pregnant woman with kyphosis who had died from myocarditis. The drawing clearly represents the specimen, having been mounted in a large glass vessel in 1922 and included in the collection of the Anatomical Institute. The current narrative on the bisected body of a pregnant woman and her fetus preserved in the Marburg Museum Anatomicum has nothing to do with the specimen in the collection. In fact, the latter was prepared in 1922 by order of the former professor of obstetrics, Wilhelm Zangemeister, who later published the case in his textbook of obstetrics. The ethical consequences of the changing ontological status and origin of the specimen and its public display are discussed.


TCR expression and clonality analysis in pulmonary sarcoidosis.
Pulmonary sarcoidosis is a granulomatous disease characterized by the accumulation of activated T cells in the lower respiratory tract. To evaluate the hypothesis that sarcoidosis is characterized by a selective activation and expansion of a limited repertoire of T cell receptor (TCR)-specific T cells, we analyzed TCRAV and TCRBV gene expression in bronchoalveolar lavage (BAL) T cells from sarcoidosis patients and, for comparison, from patients with other pulmonary diseases where lymphocyte accumulation is not observed. Increased expression of TCRAV9 and TCRAV14 in BAL T cells was observed in sarcoidosis patients compared to these controls. To ascertain whether the accumulation of AV9 and AV14 expressing BAL T cells in sarcoidosis was the result of clonal expansion, the lengths of the CDR3 regions in AV9 and AV14 transcripts were determined. Some individual patient samples showed evidence of oligoclonality. However, in most cases, the data were consistent with the presence of many different clones. These data suggest that the bulk of BAL T cells in sarcoid patients are either nonspecifically recruited or are responding to a complex mixture of antigens.


Hydrophobic and porous carbon nanofiber membrane for high performance solar-driven interfacial evaporation with excellent salt resistance.
Interfacial evaporation has recently received great interest from both academia and industry to harvest fresh water from seawater, due to its low cost, sustainability and high efficiency. However, state-of-the-art solar absorbers usually face several issues such as weak corrosion resistance, salt accumulation and hence poor long-term evaporation stability. Herein, a hydrophobic and porous carbon nanofiber (HPCNF) is prepared by combination of the porogen sublimation and fluorination. The HPCNF possessing a macro/meso porous structure exhibits large contact angles (as high as 145°), strong light absorption and outstanding photo-thermal conversion performance. When the HPCNF is used as the solar absorber, the evaporation rate and efficiency can reach up to 1.43 kg m-2h-1 and 87.5% under one sunlight irradiation, respectively. More importantly, the outstanding water proof endows the absorber with superior corrosion resistance and salt rejection performance, and hence the interfacial evaporation can maintain a long-term stability and proceed in a variety of complex conditions. The HPCNFs based interfacial evaporation provides a new avenue to the high efficiency solar steam generation.


Major bleeding risk with non-vitamin K antagonist oral anticoagulant vs. aspirin in heart failure: network meta-analysis.
Relative bleeding risks of different antithrombotic agents in heart failure (HF) patients is an important consideration in treatment decision making, making detailed comparative analysis desirable. The aim of this study was to conduct a network meta-analysis to investigate the major bleeding risk for individual novel oral anticoagulants (NOACs) vs. aspirin among patients with HF. We searched Pubmed, EMBASE, Cochrane Collaboration Central Register of Controlled Clinical Trials, and Clinicaltrials.gov from 1966 to November 2019 to identify relevant randomized clinical trials. Studies comparing individual NOACs vs. aspirin were analysed using direct study-level meta-analysis. Studies comparing aspirin to warfarin and NOACs to warfarin were then additionally added using network (direct and indirect) study-level meta-analysis. Primary endpoint was major bleeding. Final analysis included nine trials with 34 367 participants, including one direct comparison trial (apixaban vs. aspirin) and eight indirect comparison trials against the shared warfarin comparator (four aspirin trials and one trial each of apixaban, dabigatran, rivaroxaban, and edoxaban). For apixaban, network meta-analysis combing direct and indirect comparison showed that major bleeding risk might not be different between apixaban and aspirin (odds ratio, 1.18 [95% confidence interval, 0.38 to 3.65]) in HF patients. In contrast, indirect-comparison meta-analysis showed dabigatran, rivaroxaban, and edoxaban compared with aspirin might be associated with a higher risk of major bleeding in HF patients. In network meta-analysis, apixaban might be associated with a comparable risk of major bleeding compared with aspirin in patients with HF, while other NOACs might be associated with a higher risk. However, such results were not strongly convincing because of lack of direct comparison in an original trial and small sample size of trials and participants. A clinical trial directly comparing apixaban vs. aspirin in patients with HF and sinus rhythm may be worth undertaking.


Onset polarity in bipolar disorder: A strong association between first depressive episode and suicide attempts.
The role of onset polarity (OP) in patients with bipolar disorder (BD) has been increasingly investigated over the last few years, for its clinical, prognostic, and therapeutic implications. The present study sought to assess whether OP was associated with specific correlates, in particular with a differential suicidal risk in BD patients. A sample of 362 recovered BD patients was dichotomized by OP: depressed (DO) or elevated onset (EO: hypomanic/manic/mixed). Socio-demographic and clinical variables were compared between the subgroups. Additionally, binary logistic regression was performed to assess features associated with OP. DO compared with EO patients had older current age and were more often female, but less often single and unemployed. Clinically, DO versus EO had a more than doubled rate of suicide attempts, as well as significantly higher rates of BD II diagnosis, lifetime stressful events, current psychotropics and antidepressants use, longer duration of the most recent episode (more often depressive), but lower rates of psychosis and involuntary commitments. Retrospective design limiting the accurate assessment of total number of prior episodes of each polarity. Our results support the influence of OP on BD course and outcome. Moreover, in light of the relationship between DO and a higher rate of suicide attempts, further investigation may help clinicians in identifying patients at higher risk of suicide attempts.


Biological effects of the dihydroorotate dehydrogenase inhibitor polyporic acid, a toxic constituent of the mushroom Hapalopilus rutilans, in rats and humans.
Inhibitors of dihydroorotate dehydrogenase (DHO-DH), such as brequinar or leflunomide, have been intensively tested for their antitumour and immunomodulating effects. Polyporic acid (PA) from the mushroom Hapalopilus rutilans (H. r.) also is a DHO-DH inhibitor (50% inhibitory concn., IC50, 10(-4)-10(-3) M). As three people had been poisoned following ingestion of H. r. we wanted to investigate the effects of PA in rats and in cell cultures. Rats given PA via probang (100-800 mg/ kg) within 24 h developed strongly reduced locomotor activity, depressed visual placing response and impaired wire manoeuvre. Laboratory investigation of blood revealed hepatorenal failure, metabolic acidosis as well as hypokalaemia and hypocalcaemia. All symptoms closely paralleled the effects seen in the poisoned people. Proliferation of cultured cells (including rat brain neurons and glia, fibroblasts, tumour cells) was depressed at 10(-4)-10(-3) M PA. We conclude that the intoxication of people poisoned with H. r. is due to the high content of the DHO-DH inhibitor PA.


Central Nervous System Vasculitis: Primary Angiitis of the Central Nervous System and Central Nervous System Manifestations of Systemic Vasculitis.
Central nervous system vasculitis (CNSV) is a group of disorders leading to inflammatory vasculopathy within the brain, spinal cord, and leptomeninges. CNSV is divided into primary angiitis of the central nervous system (PACNS) and secondary CNSV based on the underlying etiology. PACNS is a rare inflammatory disorder with poorly understood pathophysiology and heterogeneous and highly variable clinical features. The diagnosis depends on a combination of clinical and laboratory variables, multimodal imaging, and histopathological examination as well as exclusion of mimics. Several systemic vasculitides, infectious etiologies and connective tissue disorders have been shown to cause secondary CNSV and require prompt recognition.


A new kind of paternalism in surrogate decision-making? The case of Barnsley Hospitals NHS Foundation Trust v MSP.
The modern legal and ethical movement against traditional welfare paternalism in medical decision-making extends to how decisions are made for patients lacking decisional capacity, prioritising surrogates' judgment about what patients would have decided over even their best interests. In England and Wales, the Mental Capacity Act 2005 follows this trend of prioritising the patient's prior wishes, values and beliefs but the dominant interpretation in life-sustaining treatment cases does so by in effect calling those values the 'best interests' of the patient and focusing nearly exclusively on the 'subjective' viewpoint of the patient. In this article, we examine the recent Court of Protection judgment in Barnsley Hospitals NHS Foundation Trust v MSP [2020] EWCOP 26, which adhered closely to this approach, to suggest that it could have unexpected negative consequences. These include insufficient information gathering about and attention to patients' objective medical interests, inadequacy of the evidentiary standard used for the substituted decision-making and, in some cases, even prioritising a surrogate's current substituted judgment over the potential for an actual judgment by the patient.


Reversal of alcohol's effects on neurite extension and on neuronal GAP43/B50, N-myc, and c-myc protein levels by retinoic acid.
Alcohol teratogenesis may be due in part to inhibition of neuronal differentiation by ethanol. We showed previously that alcohol decreased neuronal differentiation (neurite extension) and increased N-myc and c-myc neuronal protein levels. Since Growth-Associated Protein 43 (GAP43/B50) levels must increase for neurons to differentiate, alcohol may decrease GAP43/B50. Alcohol dose-dependently (0-0.5%) decreased GAP43/B50 protein levels by up to 92% in immature LA-N-5 cells. Five nM retinoic acid alone induced differentiation and increased GAP43/B50 levels to 230% of control. These retinoic acid-induced increases in GAP43/B50 and neurite outgrowth, and decreases in N-myc and c-myc, were reversed dose-dependently by alcohol (0-0.5%). Conversely, the adverse effects of 0.25% alcohol on neurite extension, GAP43/B50, N-myc, and c-myc were prevented by 15 and 45 nM retinoic acid. These results suggest that inhibition of neuronal differentiation by alcohol and prevention of such effects by retinoic acid are related to changes in GAP43/B50, N-myc and c-myc.


Morphology and response properties of single olivocochlear fibers in the guinea pig.
Cochlear efferent and afferent units were recorded from the spiral ganglion in anesthetized guinea pigs. Efferent units were identified by their regular discharge patterns and their long response latencies to tone bursts. In some cases these physiological criteria were confirmed by anatomical tracing of single axons labeled with horseradish peroxidase. Labeled efferent axons traveled in the vestibular nerve root and the intraganglionic spiral bundle, and crossed the tunnel to innervate up to 61 outer hair cells over longitudinal distances of 0.15 to 2.1 mm. Efferent units were subdivided into classes by their excitatory responses to monaural tone bursts. Fifty-seven percent responded only to ipsilateral-ear sound, 28% only to contralateral-ear sound, and 15% to sound in either ear. Tuning curves from efferent units were generally similar in shape to afferent units, often having equally low thresholds and equally high Q10s. Efferent Q10s were somewhat lower from preparations anesthetized with a Urethane/Innovar combination than from preparations anesthetized with a Nembutal/Innovar combination. Efferent units with spontaneous activity were uncommon at the start of the recording sessions but were more frequently encountered later in the experiments. Spontaneous activity could often be suppressed by tonal stimuli, even sometimes to the non-excitatory ear of Ipsi and Contra units.


Sebaceous gland carcinoma of the head and neck: the Princess Margaret Hospital experience.
The purpose of this study was to identify prognostic factors predicting outcomes in sebaceous gland carcinomas. We conducted a retrospective medical chart review of patients with sebaceous carcinomas of periorbital (n = 33) and extraorbital sites (n = 13). Patients with periorbital tumors had higher recurrence rates than did patients with extraorbital tumors (64% vs 23%; p = .032). Patients who were older than 60 years (p = .035) and had lower eyelid tumors (p < .0001) had a lower disease-free survival rate than did patients with upper eyelid tumors. Patients with sebaceous carcinomas had a high rate (60%) of occult lymph node metastases. Periorbital tumors are associated with poorer outcomes than are extraorbital tumors. Lower eyelid carcinomas have the worst prognosis and should be treated more aggressively. Our findings of a high incidence of occult neck disease and a high rate of regional recurrence in patients with sebaceous carcinomas support the consideration of prophylactic elective neck dissections for treating such patients.


Single-subject manual independent component analysis and resting state fMRI connectivity outcomes in patients with juvenile absence epilepsy.
The quality of fMRI data impacts functional connectivity measures and consequently, the decisions that clinicians and researchers make regarding functional connectivity interpretation. The present study used resting state fMRI to investigate resting state network connectivity in a sample of patients with Juvenile Absence Epilepsy. Single-subject manual independent component analysis was used in two levels, whereby all noise components were removed, and cerebrospinal fluid pulsation components only were isolated and removed. Improved temporal signal to noise ratios and functional connectivity metrics were observed in each of the cleaning levels for both epilepsy and control cohorts. Results showed full, single-subject manual independent component analysis reduced the number of functional connectivity correlations and increased the strength of these correlations. Similar effects were also observed for the cerebrospinal fluid pulsation only cleaned data relative to the uncleaned, and fully cleaned data. Single-subject manual independent component analysis coupled with short TR multiband acquisition can significantly improve the validity of findings derived from fMRI data sets.


Nebulin seen in DMD males including one patient with a large DNA deletion encompassing the DMD gene.
The presence of nebulin in a muscle specimen from a patient with Duchenne muscular dystrophy (DMD) due to a large deletion precludes the possibility that this protein is the DMD gene product.


Phenylalanine supply alleviates the drought stress in mustard (Brassica campestris) by modulating plant growth, photosynthesis, and antioxidant defense system.
Mustard (Brassica campestris L.) is a major oilseed crop that plays a crucial role in agriculture. Nevertheless, a number of abiotic factors, drought in particular, significantly reduce its production. Phenylalanine (PA) is a significant and efficacious amino acid in alleviating the adverse impacts of abiotic stressors, such as drought. Thus, the current experiment aimed to evaluate the effects of PA application (0 and 100 mg/L) on brassica varieties i.e., Faisal (V1) and Rachna (V2) under drought stress (50% field capacity). Drought stress reduced the shoot length (18 and 17%), root length (12.1 and 12.3%), total chlorophyll contents (47 and 45%), and biological yield (21 and 26%) of both varieties (V1 and V2), respectively. Foliar application of PA helped overcome drought-induced losses and enhanced shoot length (20 and 21%), total chlorophyll contents (46 and 58%), and biological yield (19 and 22%), whereas reducing the oxidative activities of H2O2 (18 and 19%), MDA concentration (21 and 24%), and electrolyte leakage (19 and 21%) in both varieties (V1 and V2). Antioxidant activities, i.e., CAT, SOD, and POD, were further enhanced under PA treatment by 25, 11, and 14% in V1 and 31, 17, and 24% in V2. Overall findings suggest that exogenous PA treatment reduced the drought-induced oxidative damage and improved the yield, and ionic contents of mustard plants grown in pots. It should be emphasized, however, that studies examining the impacts of PA on open-field-grown brassica crops are still in their early stages, thus more work is needed in this area.


[The effect of p-bromophenacylbromide, a phospholipase A inhibitor, in experimental acute pancreatitis in rats].
In this study the effect of p-bromophenacylbromide (p-BPAB), an inhibitor of phospholipase A, was studied in acute pancreatitis in an experimental rat model. Acute pancreatitis was produced by instillation of 0.4 ml bile into the pancreatic duct. p-BPAB was injected i.p. in a dosage of 0.25 micrograms/g b.wt. 30 min before, 30 min after, or 4h after the onset of pancreatitis. Prophylactic and early administration of p-BPAB inhibited severe morphological changes, such as necrosis and hemorrhages. Moreover, during administration of the inhibitor, decreased plasma concentrations of serum lipase and amylase (P less than 0.001) were monitored and compared with untreated animals. These therapeutic effects of p-BPAB were not seen in rats in which the inhibitor was injected 4 h after the onset of pancreatitis. As a result the phospholipase inhibitor, p-BPAB, reduces the clinical and morphological manifestations of acute pancreatitis. The effect of p-BPAB is dependent on the time of administration.


Simulation of macro EMG motor unit potentials.
Macro EMG motor unit potentials (MUPs) have been simulated. The effects on MUP parameters of number of fibres, fibre diameter, end-plate scatter, nerve branch delay, motor unit territory and electrode position have been studied. The MUP shape is sensitive to electrode position in the vicinity of the end-plates. It is mainly reflecting the end-plate scatter and the nerve delays. Away from the end-plates the wave shape is principally determined by the fibre diameter distribution. Total number of muscle fibres and their mean diameter act as gain factors at all recording positions. In the simulations the area of the signal appears to be a better measure of the strength of the motor unit than the amplitude. Macro EMG offers a much less selective recording than conventional EMG and single fibre EMG and therefore new aspects of the motor unit can be quantified. Preliminary results from simulations of neuromuscular disorders are consistent with actual findings.


A Rapid and Cost-Effective Method for DNA Extraction from Archival Herbarium Specimens.
Here we report a rapid and cost-effective method for the extraction of total DNA from herbarium specimens up to 50-90-year-old. The method takes about 2 h, uses AMPure XP magnetic beads diluted by PEG-8000- containing buffer, and does not require use of traditional volatile components like chloroform, phenol, and liquid nitrogen. It yields up to 4 µg of total nucleic acid with high purity from about 30 mg of dry material. The quality of the extracted DNA was tested by PCR amplification of 5S rRNA and rbcL genes (nuclear and chloroplast DNA markers) and compared against the traditional chloroform/isoamyl alcohol method. Our results demonstrate that the use of the magnetic beads is crucial for extraction of DNA suitable for subsequent PCR from herbarium samples due to the decreasing inhibitor concentrations, reducing short fragments of degraded DNA, and increasing median DNA fragment sizes.


Induced and constitutive heat shock protein expression in the olfactory system--a review, new findings, and some perspectives.
Heat shock, or stress, proteins (HSPs) are cellular proteins induced in response to conditions that cause protein denaturation, and their induction is essential for survival of such conditions. In the olfactory system we have found intense HSP expression occurs during normal processing of environmental odorants/inhalants as well as following hyperthermia and drug exposure. The HSPs involved include ubiquitin, HSP70, HSC70, and HSP25. Responses are both cell type- and stress-specific, occurring primarily in olfactory supporting cells and to some extent in Bowman's gland acinar cells. Responses to these stresses are not seen in olfactory sensory neurons. This article reviews those studies and the significance of their findings. It also discusses a distinct subpopulation of rat olfactory sensory neurons (OSNs), the 2A4(+)OSNs, found to be constitutively reactive with HSP70, the predominantly stress-inducible isoform of the 70 kD HSP family. Their high HSP70 expression appears to confer on the 2A4(+)OSNs an enhanced ability to survive damage-induced OSN turnover. New findings are also presented on HSP25-specific changes following olfactory bulbectomy. All data are discussed in the context of the overall olfactory and bioprotective functions of the olfactory mucosa.


Oxygen quenching of sensitized terbium luminescence in complexes of terbium with small organic ligands and proteins.
Oxygen does not quench the luminescence of either free Tb or of Tb bound to dipicolinate. However, sensitized Tb luminescence in complexes of that ion with elastase, thermolysin, and alpha-amylase is quenched by oxygen at rates that far exceed that with which the intrinsic fluorescence of the proteins is quenched. We infer that this more rapid quenching of Tb luminescence indicates a major role for energy transfer from tryptophan moieties in a triplet excited state.


The relationship between maternal dietary patterns during pregnancy in women with gestational diabetes mellitus and infant appetitive feeding behaviour at 6 months.
Early dietary exposure may influence infant appetitive feeding behaviour, and therefore their later health. Maternal diabetes in pregnancy is associated with an increased risk of obesity in the offspring. We, therefore, examined third-trimester dietary patterns of women with gestational diabetes, their offspring's appetitive feeding behaviour at 6 months of age, and relationships between these. We used data from a prospective cohort of women with gestational diabetes and assessed maternal dietary patterns at 36 weeks' gestation using principal component analysis; infant appetitive feeding behaviour at 6 months of age using the Baby Eating Behaviour Questionnaire; and relationships between these using general linear modelling and chi-square tests. In 325 mother-infant dyads, we identified three distinct maternal dietary patterns: 'Junk,' 'Mixed,' and 'Health-conscious.' The maternal 'Health-conscious' pattern was inversely associated with 'enjoyment of food' in their sons (β - 0.24, 95% CI - 0.36 to - 0.11, p = 0.0003), but not daughters (β - 0.02, 95% CI - 0.12 to 0.08, p = 0.70), and was positively associated with 'slowness in eating,' (β 0.13, 95% CI 0.02 to 0.24, p = 0.01). Third-trimester dietary patterns in women with gestational diabetes may have sex-specific effects on infant appetitive feeding behaviour at 6 months of age.


Potential MR pitfall in relying on lesion/liver intensity ratio in presence of hepatic hemochromatosis.
We present a case of hepatic metastasis studied by magnetic resonance imaging in which a spuriously high lesion/liver intensity ratio (suggestive of cavernous hemangioma) was obtained due to underlying hemochromatosis.


Hypofractionated Stereotactic Radiotherapy for Patients with Intracranial Meningiomas: impact of radiotherapy regimen on local control.
We evaluated efficacy and tolerance of hypofractionated stereotactic radiation treatment (hFSRT) in the management of intracranial meningiomas. Between December 2008 and June 2016, 126 patients with 136 intracranial meningiomas were treated with robotic hFSRT. hFSRT was performed as primary irradiation and as a salvage option for the local recurrence after prior radiotherapy. The median prescription dose was 25 Gy (12-40) with a median number of fractions of 5 (3-10). After a median follow-up of 20.3 months (range 1-77 months), the 24-months local control (LC) rate was 81% in the primary hFSRT group and 39% after hFSRT in the re-irradiation group (p=0.002). The clinical control rate of symptoms in the overall population was 95% (95% CI: 89-98%). Progression-free survival (PFS) in the overall population at 24 months was 70% (95% CI: 60%-79%). In the primary hFSRT group, PFS was significantly lower with the most hypofractionated schedules of 21-23 Gy in 3 fractions vs. 25-40 Gy in 5-10 fractions: 62% vs. 92% (p = 0.0006). The incidence of radionecrosis at 24 months was significantly lower in the primary hFSRT group, at 2% vs. 20% in the re-irradiation hFSRT group (p = 0.002).


Data on prognostic factors associated with 3-month and 1-year mortality from infective endocarditis.
This article describes supplementary tables and figures associated with the research paper entitled "Impact of referral bias on prognostic studies outcomes: insights from a population-based cohort study on infective endocarditis". The aforementioned paper is a secondary analysis of data from the EI 2008 cohort on infective endocarditis and aimed at characterising referral bias. A total of 497 patients diagnosed with definite infective endocarditis between January 1st and December 31st 2008 were included in EI 2008. Data were collected from hospital medical records by trained clinical research assistants. Patients were divided into three groups: admitted to a tertiary hospital (group T), admitted to a non-tertiary hospital and referred secondarily to a tertiary hospital (group NTT) or admitted to a non-tertiary hospital and not referred (group NT). The pooled (NTT+T) group mimicked studies recruiting patients in tertiary hospitals only. Two different starting points were considered for follow up: date of first hospital admission and date of first admission to a tertiary hospital if any (hereinafter referred to as "referral time"). Referral bias is a type of selection bias which can occur due to recruitment of patients in tertiary hospitals only (excluding those who are admitted to non-tertiary hospitals and not referred to tertiary hospitals). This bias may impact the description of patients' characteristics, survival estimates as well as prognostic factors identification. The six tables presented in this paper illustrate how patients' selection (population-based sample [pooled (NT+NTT+T) group] versus recruitment in tertiary hospitals only [pooled (NTT+T) group]) might impact Hazards Ratios values for prognostic factors. Crude and adjusted Cox regression analyses were first performed to identify prognostic factors associated with 3-month and 1-year mortality in the whole sample using inclusion as the starting point. Analyses were then performed in the pooled (NTT+T) group first using inclusion as the starting point and finally using referral time as the starting point. Figures 1 to 3 illustrate how HR increase with time for covariates that were considered as time-varying covariates (covariate*time interaction).


The Effect of Developmental Delay and Autism Spectrum Disorder on External Auditory Canal Foreign Body Extraction.
To determine the effect of developmental delay (DD) and autism spectrum disorder (ASD) on pediatric external auditory canal foreign body (EAC FB) retrieval outcomes. A retrospective chart review of children presenting with EAC FB at a tertiary children's hospital was performed between January 2018 and December 2019. Charts were reviewed for demographics, presence of otalgia, complications, number of EAC FB episodes, indications for operating room removal, DD, and ASD status. A total of 1467 patients underwent EAC FB removal. One hundred thirty-seven children (9.3%) had DD, and, of those with DD, 63 (46%) had ASD. Children with DD were 1.76 years older compared with children with non-DD (NDD) ( P < 0.0001) at the time of presentation, whereas children with ASD were 1.45 years older than children with NDD ( P = 0.0023). Children with DD and ASD were more likely to require removal of FB in the operating room (OR) compared with the NDD group (36.5% vs 16.7%, P = 0.0001). This was not true for children with DD without ASD. Patients with DD reported significantly less otalgia when compared with NDD patients (26.3% vs 37.4%, P = 0.0097). A similar trend, although not statistically significant, was observed when comparing children with ASD with NDD patients. The NDD patients (1.1) had fewer EAC FB episodes than patients with DD (1.6, P < 0.0001) and ASD (1.8, P < 0.0016). Hazard ratios for multiple episodes of FB were 4.5 (95% confidence interval, 2.9-6.8) for DD, and 5.6 for ASD (95% confidence interval, 3.2-9.9). The complication rate for all groups was low. Due to the different ways that children with DD and ASD present compared with NDD children, physicians should be vigilant when evaluating symptoms and conducting physical examinations for EAC FB in those patients. A lower threshold for referral to otolaryngologists may result in more favorable outcomes.


Blood coagulation abnormalities associated with envenoming by Trimeresurus albolabris in Hong Kong.
Snake bites in Hong Kong are most commonly due to Tr. albolabris (White-lipped pit viper, bamboo snake). We studied 21 cases of envenoming by Tr. albolabris prospectively in order to document the incidence and severity of associated coagulation abnormalities. Eighteen patients (86%) had increased blood concentrations of fibrin degradation products (FDP) ranging from 10-40 micrograms/l to greater than 200 micrograms/l (normal: less than 10 micrograms/l), the majority of whom also had detectable soluble fibrin monomers. Among these 21 patients, 10 had decreased blood concentrations of fibrinogen ranging from 0.3 kg/l to 1.9 g/l (normal: 2-4 gl/l). In 11 cases (52%), the euglobulin clot lysis time was shortened (less than 150 minutes) in association with elevated blood concentrations of FDP (n = 10) and decreased circulating fibrinogen levels (n = 8). Thrombocytopenia and/or prolongation of prothrombin time (PT), activated partial thromboplastin time (APTT) and/or thrombin time (TT) were present in 10 patients (28%). Increased blood concentrations of FDP and decreased circulating fibrinogen levels were present in most of these cases. Envenoming by Tr. albolabris is therefore frequently associated with a coagulopathy compatible with increased fibrin/fibrinogenolysis. Measurement of blood concentrations of FDP is the most sensitive test for detecting the coagulopathy. There is, however, little correlation between the patterns of clinical manifestations and coagulation abnormalities although more severe clinical features were usually associated with high circulating FDP levels. Only one patient developed systemic bleeding but no fatality was observed. The coagulation abnormalities are usually correctable by replacement therapy. Further studies are required to study the mechanisms of this coagulopathy and its relationship with venom antigenaemia.


Size for gestation in Aboriginal babies: a comparison of two papers.
Two recent papers examining low birthweight in Aboriginal infants came to different conclusions about the role of size for gestation and preterm delivery in influencing the low birthweight proportion. As the two studies used different methods to estimate the infants' gestational age and to analyse the data, the results cannot be compared directly. This analysis combines the methods of both earlier studies. Data collected in 6 Top End communities were analysed to calculate the proportion of infants who were small for gestational age. Despite the high overall prevalence of preterm delivery from the midwives' estimates, 31.4% of infants fell below the 10th centile of weight for gestational age and sex. The majority of these infants were not low birthweight. The earlier report from the Top End of high proportions of small-for-gestational age infants cannot be dismissed as an artefact due to the method of estimating gestational age. Intervention programs to improve birth weights in Aboriginal infants need to address both conditions--small size for gestational age and preterm delivery--and need to target the whole population rather than high risk pregnancies.


Zwitterionic capsular polysaccharides: the new MHCII-dependent antigens.
The immune system has evolved the ability for T cells to recognize nearly any biological polymer, including peptides, protein superantigens, and glycolipids through presentation by the major histocompatibility complex (MHC) proteins such as MHC class I (MHCI), MHC class II (MHCII), and CD1. A recent and unexpected addition to this list is the zwitterionic capsular polysaccharide (ZPS). These bacterial molecules utilize MHCII presentation to activate T cells via recognition by alphabeta T cell receptor (alphabetaTCR) proteins. In this review, we explore what is currently known about ZPS processing and presentation within antigen-presenting cells (APCs) and the immune response that follows.


The timing of demise in fetuses with trisomy 21 and trisomy 18.
Women with chromosomally abnormal fetuses often choose to continue their pregnancy. However, though they may search for specific details whether their fetus will survive, not much information is available. We sought to determine if there was a pattern for timing of demise and to determine if demise was more likely to occur before viability in fetuses with amniocentesis confirmed trisomy 18 or 21. From the California Expanded AFP screening program, 1813 women were identified to have a fetus with trisomy 18 or 21. Of these, 392 women with trisomy 21 and 106 with trisomy 18 continued the pregnancy. Pregnancies ending in fetal demise were analyzed for gestational age at demise. Of the trisomy 21 fetuses, 40 (10.2%) demised and of the trisomy 18 fetuses, 34 (32.1%) demised. The mean gestational age at time of fetal demise was 28.9+/-1.3 weeks SE for trisomy 21 and 32.1+/-1.2 weeks SE for trisomy 18 (p=0.09). There was no clustering of losses as losses were uniformly distributed throughout gestation after 24 weeks. A slightly larger proportion of T-21 (37.1%) losses occurred before viability (24 weeks) compared to those with T-18 (14.8%) (p=0.05). It appears that after 24 weeks' gestation, there is no specific time for fetal demise in fetuses affected by trisomy 21 or 18. There may be an association between trisomy 21 and stillbirth prior to viability. This information may be helpful in counseling those patients found to have a chromosomally abnormal fetus who choose to continue their pregnancy.


Pig Cloning Using Somatic Cell Nuclear Transfer.
Porcine cloning technology can be used to produce progenies genetically identical to the donor cells from high-quality breeding pigs. In addition, genetically modified pigs have been produced by somatic cell nuclear transfer using genetically modified porcine fetal fibroblasts. The method of preparing genetically modified pigs is critical for establishing pig models for human diseases, and for generating donor animals for future xenotransplantation. This chapter describes detailed procedures for generating cloned pigs using fetal fibroblasts as nuclear donors.


Attenuation of social interaction-associated ultrasonic vocalizations and spatial working memory performance in rats exposed to chronic unpredictable stress.
Exposure to unpredictable chronic mild stress (CUS) is a commonly used protocol in rats that is reported to evoke antidepressant-reversible behaviors such as loss of preference for a sweetened water solution which is taken as an analog of the anhedonia seen in major depression. However, the induction of anhedonic-like behavior by chronic mild stress, gauged by an animal's preference for sucrose solution, is not fully reproducible and consistent across laboratories. In this study, we compared a widely used behavioral marker of anhedonia - the sucrose preference test, with another phenotypic marker of emotional valence, social interaction-associated ultrasonic vocalizations as well as a marker of an anxiety-like phenotype, novelty-suppressed feeding, and cognitive performance in the eight arm radial maze task in adult male Sprague-Dawley rats. Chronic four-week exposure to unpredictable mild stressors resulted in 1) attenuation of social interaction-associated ultrasonic vocalizations 2) attenuation of spatial memory performance on the radial arm maze 3) attenuation of body weight gain and 4) increased latency to feed in a novelty-suppressed feeding task. However, chronic exposure to CUS did not result in any significant change in sucrose preference at one-week and three-week intervals. Our results argue for the utility of ultrasonic vocalizations in a social interaction context as a comparable alternative or adjunct to the sucrose preference test in determining the efficacy of CUS to generate an anhedonic-like phenotypic state.


Enhancement of phytohemagglutinin and concanavalin A responses of splenic lymphocytes by adherent cell removal.
Removal of glass wool-adherent cells resulted in an enhancing effect on DNA synthesis as measured by increased [3H]-thymidine uptake by normal swine spleen cells stimulated with phytohemagglutinin or concanavalin A (Con A). Depletion of nylon-adherent cells caused decreased DNA synthesis in response to Con A, except at high doses of Con A, whereas similar cultures stimulated with phytohemagglutinin showed enhanced DNA synthesis throughout the dose range employed. Titration experiments revealed that enhancing effects of adherent cell removal are most pronounced at higher cell and mitogen concentrations. Glass wool was more efficient than nylon in the enhancement of mitogen-induced DNA synthesis.


Induction of retinochoroidal venous anastomosis in central retinal vein occlusion with macular edema via a full-thickness retinochoroidal incision.
To report the induction of retinochoroidal venous anastomosis (RCVA) in the treatment of nonischemic central retinal vein occlusion (CRVO) with macular edema via a full-thickness retinochoroidal incision. In nine eyes with nonischemic CRVO and intractable macular edema, one or two full-thickness incisions transacting a major retinal branch vein to the level of inner sclera were made in conjunction with vitrectomy. Fluorescein angiography was conducted to evaluate the formation of functional RCVA. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were compared before and after the surgery. The mean follow-up period +/- SD was 12.0 +/- 5.1 months. All nine eyes developed functional RCVA after the surgery. The mean BCVA +/- SD improved from 0.75 +/- 0.30 logMAR (logarithm of the minimal angle of resolution) to 0.55 +/- 0.26 logMAR (P = 0.018), and the mean CMT +/- SD was reduced from 686 +/- 265 microm to 251 +/- 150 microm (P = 0.011). Additional surgery was performed on one eye due to persistent vitreous hemorrhage. Full-thickness retinochoroidal incision appears to raise the rate of successful RCVA formation and may improve the outcome of CRVO with macular edema.


Is percutaneous computed tomography-guided biopsy sufficient to establish indolent lymphoma transformation?
The aim of the study was to retrospectively evaluate the technical features, efficacy, accuracy, and relevant complications of computed tomography-guided biopsies in various anatomical localizations when diagnosing indolent lymphoma transformations, relapses, duplicate malignant diseases or benign processes. From December 2007 to December 2017, 81 percutaneous biopsy procedures in 72 patients for tumors, sizes 17-232 mm in diameter (median length: 39 mm), were performed in patients with known indolent lymphomas in their clinical history. The patients were men in 41 cases and women in 31 cases, aged 36 to 86 years. In 79 cases (97.5%; 95% CI: 91.3-99.7) results were true positive or true negative; only 2 interventions (2.5%; 95% CI: 0.3-8.6) were histologically false negative. Transformation was verified in 29 cases (35.8%; 95% CI: 25.4-47.2), relapses in 30 cases (37%; 95% CI: 26.6-48.5), duplicate malignancy in 15 cases (18.5%; 95% CI: 10.8-28.7) and benign processes in 7 cases (8.7%; 95% CI: 3.5-17.0). Eight complications in total were revealed, 7 of which were in consequence of thoracic cavity biopsy. A statistically significant relationship between the complication incidence and anatomical localization in the thoracic cavity was identified (p = 0.0104). Percutaneous CT guided biopsy performed in patients with a history of indolent lymphoma had high accuracy in establishing the correct diagnosis regarding transformation, relapse, duplicate malignancy or a benign process. Simultaneously, the complication rate was low.


Intensity modulated radiotherapy and 3D conformal radiotherapy for whole breast irradiation: a comparative dosimetric study and introduction of a novel qualitative index for plan evaluation, the normal tissue index.
We report on a retrospective dosimetric study, comparing 3D conformal radiotherapy (3DCRT) and hybrid intensity modulated radiotherapy (hIMRT). We evaluated plans based on their planning target volume coverage, dose homogeneity, dose to organs at risk (OARs) and exposure of normal tissue to radiation. The Homogeneity Index (HI) was used to assess the dose homogeneity in the target region, and we describe a new index, the normal tissue index (NTI), to assess the dose in the normal tissue inside the tangent treatment portal. Plans were generated for 25 early-stage breast cancer patients, using a hIMRT technique. These were compared with the 3DCRT plans of the treatment previously received by the patients. Plan quality was evaluated using the HI, NTI and dose to OARs. The hIMRT technique was significantly more homogenous than the 3DCRT technique, while maintaining target coverage. The hIMRT technique was also superior at minimising the amount of tissue receiving D 105% and above (P < 0.0001). The ipsilateral lung and contralateral breast maximum were significantly lower in the hIMRT plans (P < 0.05 and P < 0.005), but the 3DCRT technique achieved a lower mean heart dose in left-sided breast cancer patients (P < 0.05). Hybrid intensity modulated radiotherapy plans achieved improved dose homogeneity compared to the 3DCRT plans and superior outcome with regard to dose to normal tissues. We propose that the addition of both HI and NTI in evaluating the quality of intensity modulated radiotherapy (IMRT) breast plans provides clinically relevant comparators which more accurately reflect the new paradigm of treatment goals and outcomes in the era of breast IMRT.


Periodontal ligament cells under intermittent tensile stress regulate mRNA expression of osteoprotegerin and tissue inhibitor of matrix metalloprotease-1 and -2.
We studied the mRNA expression of osteoprotegerin (OPG), receptor activator of NF-kappa B ligand (RANKL), tissue inhibitor of matrix metalloprotease (TIMP)-1 and -2, and matrix metalloprotease (MMP)-1 and -2 by human periodontal ligament (PDL) cells under intermittent tensile stress using a Flexercell Strain Unit. Analysis by reverse transcriptase-polymerase chain reaction showed that mechanical force upregulated OPG mRNA. We also demonstrated that the protein concentration of OPG in conditioned medium increased upon loading with tensile stress, as determined by enzyme-linked immunosorbent assay. TIMP-1 and -2 mRNA levels also increased, whereas levels of RANKL, MMP-1, and MMP-2 mRNA were barely affected. We further examined the effect of loading with tensile stress and addition of Salmonella abortus equi lipopolysaccharide (LPS) on the mRNA expression of PDL cells. The amount of OPG mRNA induced by mechanical strain was found to decrease with the addition of LPS to cultures. The induction of OPG mRNA expression by stretching was inhibited in the presence of indomethacin or genistein, whereas TIMP-1 mRNA expression induced by stretching was inhibited by the addition of cycloheximide, suggesting that tensile stress regulates cyclooxygenase activities, tyrosine phosphorylation, and de novo protein synthesis in PDL cells through the induction of OPG and TIMP-1 mRNA expression. These results provide evidence that the mechanical stimulus of stretching is responsible for the observed regulation of bone resorption and tissue degradation in PDL tissue.


Is the Problem Cultural Incompetence or Racism?
Clinical competence-including asking about and understanding the impact of a patient's culture-should be what we all expect when we seek treatment. Behavioral health organizations have opportunities to create culturally competent and responsive services. But we need to add another call to action-acknowledging and addressing the disparities caused by racism.