Bilateral swelling of the salivary glands and sicca symptoms: an unusual differential diagnosis-Kimura's disease, a rare allergic condition with a high IgE serum level-a case report and review of the literature.
A 68-year-old woman presented with bilateral swelling of the salivary glands, sicca symptoms of eyes and mouth, itching, fatigue and weight gain of about 5 kg in the last 2-3 years. As part of a careful diagnostic work up including lab tests for antinuclear antibodies (ANA), antibodies to extractable nuclear antigens (ENA), anti-neutrophilic cytoplasmatic antiobodies (ANCA), immunoglobulin (Ig)G4, a whole body computed tomography (CT) and a parotid biopsy several rheumatic diseases such as Sjoegren's syndrome, IgG4-related disease and sarcoidosis were ruled out and, considering a very high titre of IgE, Kimura's disease was diagnosed. The case and a short review of the literature are presented.


Anti-apoptotic PTD-FNK protein suppresses lipopolysaccharide-induced acute lung injury in rats.
The present study was aimed at clarifying the effects of an anti-apoptotic protein for modulating symptoms in acute lung injury (ALI). From Bcl-x(L), a Bcl-2 family member, we constructed an artificial protein (FNK) and fused it with the protein transduction domain (PTD) of the HIV/Tat protein (PTD-FNK) to facilitate its permeation into cells. ALI was induced by intratracheal infusion of lipopolysaccharide (LPS) into Sprague-Dawley male rats. PTD-FNK was injected into the peritoneal cavity of the animals either 2 h before, or 3 h or 6 h after LPS challenge. All rats were sacrificed 24 h after the last treatment. Cell differential ratios and albumin concentration were estimated in bronchoalveolar lavage fluid. We examined histological change, myeloperoxidase activity, TUNEL assay, caspase-3/caspase-3-like activity and immunohistochemical reaction for caspase 3 (active form). In animals with PTD-FNK treatment, the albumin leakage was significantly attenuated with protection of tissue damage. Also, the apoptosis of alveolar wall cells was reduced by PTD-FNK treatment, while a total cell number and the neutrophil ratio were not changed. Human umbilical vein endothelial cells (HUVEC) and cells of an alveolar epithelial cell line (A549) were exposed to LPS or TNF-alpha with or without PTD-FNK treatment in vitro. Cell survival rates examined by trypan-blue exclusion assay were increased by PTD-FNK treatment in a concentration-dependent manner. Thus, PTD-FNK could play a protective role in ALI by suppressing apoptosis of alveolar epithelial cells and capillary endothelial cells despite of some effect on neutrophil activity.


Adenocarcinoma of the gastric pouch 26 years after loop gastric bypass.
A 61-year-old woman presented 29 years after loop gastric bypass with a cancer of the gastric pouch. The cancer was removed by en bloc resection of the pouch, residual stomach and involved transverse colon with Roux-en-Y esophago-jejunal reconstruction. Very few cases of gastric cancer have been reported following gastric bypass for obesity. This case represents the first reported gastric cancer arising in the gastric pouch following loop gastric bypass.


The efficacy of personalized audiovisual patient-education materials.
Patient education is considered an important component of primary care medicine. The traditional methods of patient education have been physician-patient dialogue and printed handouts. This study compares the relative efficacy of pamphlets, one-to-one dialogue, and audiovisual presentations. The results indicate that the slide and sound presentation was most effective in conveying patient information.


Differential expression of neuronal fos protein after cold water drowning and controlled rewarming.
Cardiopulmonary bypass has often been applied to revive victims of cold water drowning. The success of resuscitative efforts in patients who have sustained severe hypothermia is largely determined by neurologic outcomes. Measurement of Fos, the protein product of the immediate-early gene c-fos, is a marker of cerebral injury. Twenty-eight infant lambs were sedated and ventilated. Group 1 lambs were immersed in a cold water bath for 2 hours (17.3 +/- 2.7 degrees C). Group 2 lambs were placed on normothermic cardiopulmonary bypass for 2 hours (37.7 degrees +/- 0.7 degrees C). Group 3 lambs were immersed in a cold water bath for 2 hours (17.6 degrees +/- 2.4 degrees C), and then rewarmed for a period of 2 hours on cardiopulmonary bypass (37.0 degrees +/- 0.6 degrees C). The lambs were euthanized and immunohistochemical analysis for neuronal Fos was performed. There was significant induction of Fos-labeled nuclear profiles (cells/1130 microm(2)) in group 3 in the hippocampal regions and dentate gyrus compared with groups 1 and 2 (p < 0.001). Isolated exposure to either hypothermia or cardiopulmonary bypass results in minimal expression of neuronal Fos; the significant induction of Fos in the group 3 animals may represent an ischemic-reperfusion phenomenon. Modifications of rewarming techniques that minimize Fos expression may improve neurologic outcomes in victims of cold water drowning.


Semi-automated segmentation and classification of digital breast tomosynthesis reconstructed images.
Digital breast tomosynthesis (DBT) is a limited-angle tomographic x-ray imaging technique that reduces the effect of tissue superposition observed in planar mammography. An integrated imaging platform that combines DBT with near infrared spectroscopy (NIRS) to provide co-registered anatomical and functional imaging is under development. Incorporation of anatomic priors can benefit NIRS reconstruction. In this work, we provide a segmentation and classification method to extract potential lesions, as well as adipose, fibroglandular, muscle and skin tissue in reconstructed DBT images that serve as anatomic priors during NIRS reconstruction. The method may also be adaptable for estimating tumor volume, breast glandular content, and for extracting lesion features for potential application to computer aided detection and diagnosis.


A novel near-infrared fluorescent probe with hemicyanine scaffold for sensitive mitochondrial pH detection and mitophagy study.
Mitochondria, as an energy-producing powerhouse in live cells, is considered to be directly linked to cellular health. However, dysfunctional mitochondria and abnormal mitochondria pH would possibly activate mitophagy, cell apoptosis and intercellular acidification process. In this work, we synthesized a novel near infrared fluorescent probe (FNIR-pH) for measurement of mitochondrial pH based on the hemicyanine skeleton as a fluorophore. The FNIR-pH probe functioned as a mitochondrial pH substrate and exhibited quick and sensitive turn-on fluorescence responses to mitochondrial pH in basic solution due to the deprotonation of hydroxy group in the structure. From pH 3.0 to 10.0, the FNIR-pH exhibited almost 100-fold increase in fluorescence intensity at 766 nm wavelength. The FNIR-pH also displayed superior selectivity to various metal ions, excellent photostability, and low cytotoxicity, which facilitated further biological application. Owing to the proper pKa value of 7.2, the FNIR-pH paved the way for real-time monitoring of mitochondria pH changes in live cells and sensitive sensing of mitophagy. Moreover, the FNIR-pH probe was also implemented for fluorescent imaging of tumor-bearing mice to validate its potential application for in vivo imaging of bioanalytes and biomarkers.


Four characteristics of vascular echo suggesting arterial thromboembolism: differentiation from aggravation of atherosclerotic peripheral artery disease.
Arterial thromboembolism (ATE) leading to acute arterial occlusion can involve life-threatening complications, including limb loss and death, without prompt thrombectomy. Several ATEs are hard to differentiate from acute aggravation of atherosclerotic peripheral artery disease (PAD). We determined four characteristics of vascular echos suggesting ATE for the differentiation from PAD and validated their use. Twenty patients (11 men and 9 women; mean age, 74 years) with ATE confirmed by therapeutic findings and 19 patients with PAD including occlusive lesions (14 men and 5 women; mean age, 78 years) were enrolled. Four hallmarks of vascular echo suggesting ATE were defined as the manifestation of the intima-media complex next to the adventitia (M1), mild to moderate echolucency of the intravascular structure (M2), mobility of the intravascular structure (M3), and the pulsatile movement of the arterial wall (M4) in occlusive arterial lesions. In the ATE group, 6 patients had three positive items, and 14 patients had four positive items. In the PAD group, ten patients had no positive items, and nine patients had one positive item. Using a cutoff score of more than 3 for ATE, the sensitivity was 100%, the specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 100%. The presented characteristics of vascular echo suggesting ATE could be useful for making the differential diagnosis against PAD.


Age-related morphologic changes of the vertebral artery in the transverse process. Analysis by multidetector computed tomography angiography.
The V2 segment of the vertebral artery (VA) ascends and passes through the transverse foramen (TF) of the C6-C1 vertebrae. Atherosclerosis of the VA and degenerative changes in the cervical spine are likely to occur with aging, and subsequent morphologic changes may alter the normal anatomy. The aim was to determine the morphologic changes of TF and VA in relation to aging. This was a retrospective cross-sectional study. One hundred ten consecutive patients who had undergone computed tomography angiography were included. The subjects were then divided into three groups according to age: Group A, less than 45 years; Group B, from 45 to 65 years; and Group C, older than 65 years. Cases with stenosis and dissection of the VA were excluded from the quantitative analysis. The areas of the VA and TF were measured, and the VA/TF occupation ratio (OR) was calculated accordingly. The presence of VAs tortuosity within the TF was also noted. The TF was larger in the oldest group, but the difference was not statistically significant. There was also no significant statistical difference among the age groups in terms of the VA and VA/TF ORs (p>.05). In the Group C, the rate of overall tortuosity of the VA was 73%, and arterial tortuosity in the TF was 28.6%. In cases with tortuous VA, C6 and C4 TFs were found to be significantly larger. Tortuous VAs tend to be associated with enlargement of C6 and C4 TFs. Knowledge of such changes in the anatomy is crucial during instrumentation used for cervical spine surgeries, to prevent serious complications in patients aged older than 65 years.


Facial Injuries in Sports, Soft Tissue Injuries (Abrasions, Contusions, Lacerations).
This article reviews the diagnosis and treatment of facial soft tissue injuries in athletics. General diagnostic algorithms are presented, including initial assessment aligned with Advanced Trauma Life Support guidelines. Specific injury types are discussed along with possible collateral damage and adverse sequelae to limit morbidity. Treatment modalities are described using generally accepted principles refined to fit athlete patients. Return-to-play issues are outlined relative to level of participation, with the emphasis on safe return. Goals of treatment are defined, including prompt, accurate diagnosis; efficient, effective treatment; safe return; and optimum functional and esthetic outcome.


Emergence, Reduction and the Identity and Individuation of Powers.
One recently popular way to characterise strong emergence is to say that emergent entities possess novel causal powers. However, there is little agreement concerning the nature of powers. One controversy involves whether powers are single- or multi-track; that is, whether each power has only one manifestation type, or whether a single power can be directed towards a number of distinct manifestations. Another concerns how powers operate: whether a lone power manifests when triggered by the presence of a suitable stimulus, or whether powers operate mutually such that several powers must 'work together' to bring about a particular manifestation. This paper examines how these distinctions-which can be cross-combined to frame four distinct accounts of the nature of powers-bear on the debate between emergentists and reductionists.


Passively acquired antibody directed at human erythrocytes seen during therapy with Minnesota antilymphoblast globulin.
6 renal transplant patients, seen at the Mayo Clinic between July 1982 and April 1983, received Minnesota antilymphoblast globulin (MALG) for treatment of allograft rejection and demonstrated warm-acting 'auto'-antibodies during such therapy. These antibodies represented xenogeneic reactivity in equine MALG, rather than the products of patient-derived immune responses, since they were not detected before or after the period of therapy with this immunosuppressive agent in any of the 6 cases. They interfered with crossmatch procedures for red cell transfusion, and were only variably removed by autoabsorption techniques. Heat treatment of sera containing MALG-related red cell antibodies was ineffective in abrogating their reactivity and also compromised the reactivity of some red cell alloantibodies which were tested as controls. Transfusion of 'least-incompatible' red blood cells had no adverse effects in 2 cases where it was necessitated by clinical circumstances, despite an inability to obtain suitable serological samples for crossmatching.


In vivo confocal laser microscopy of morphologic changes after small incision lenticule extraction with accelerated cross-linking (SMILE Xtra) in patients with thin corneas and high myopia.
To evaluate the microstructural modifications and safety of small incision lenticule extraction combined with accelerated cross-linking (SMILE Xtra) in high myopia and thin corneas by means of in vivo confocal microscopy (IVCM) and 3D-OCT after a 6-month follow-up. Forty-three eyes with high myopia and thin corneas were enrolled. All eyes underwent SMILE procedure. After the lenticule was extracted, 0.25% riboflavin was injected into the interface and allowed to diffuse for 60 s. The eye was irradiated with UVA radiation of 30 mW/cm2 for 90 s through the cap. The total energy delivered was 2.7 J/cm2. Morphologic modifications of corneal architecture were evaluated prior to SMILE Xtra and 7 days, 1, 3, and 6 months after SMILE by in vivo confocal microscopy (IVCM) and 3D-OCT. The corneal epithelial cells showed slight damage until 3 months postoperatively. The subepithelial nerve plexus decreased but no absence within the treatment zone at the first week after treatment, recolonized at 3 months postoperatively, and had mostly recovered at the 6 months postoperative but remained less than its normal baseline state. Keratocytes were absent in the surgical interface area, and the presence of strong reflective particles and cicatricial reaction in the anterior stroma were observed during the entire 6-month examination period. Increased hyperreflectivity was observed from the cap side at a depth of 60 µm to stroma bed at a depth of 388 µm through 6 months. The depth of the demarcation line in 40 eyes (93.0%) was at a mean depth of 296.12 ± 47.86 μm (range, 211-388 μm). No particular change between preoperative and postoperative corneal endothelium was observed. Confocal microscopy showed increased hyperreflectivity in the SMILE Xtra eyes, and no changes in corneal endothelium. We confirmed the safety of the SMILE Xtra but recognize that larger and longer-term studies of SMILE Xtra are necessary.


Normative reference values and regression equations to predict the 6-minute walk distance in the Asian adult population aged 21-80 years.
The 6-min walk test (6MWT) is a widely used field walking test. This study reports the normative reference values (NRV) of distance walked during 6MWT (6MWD) in healthy Singaporeans (aged 21-80) and updates the 6MWD reference equations. This information may facilitate the interpretation of the 6MWD in clinical populations. The Singapore Institute of Technology-Institutional Review Board (SIT-IRB Project Number: 2019099) approved this study to be carried out from June 2019 to January 2021. All participants gave written informed consent before data collection began. The six-minute walk test (6MWT) is a widely adopted submaximal field-walking test to evaluate functional exercise capacity. This validated test is a reliable, safe, inexpensive, and straightforward assessment tool commonly used as an outcome measure, using the distance walked (6MWD) as the primary outcome. An earlier study has established the normative reference values (NRV) and equation in healthy Singaporeans - however, the small sample size and narrow age range curb adequate representation of the adult population profile. This study aims to update the NRV and reference equations to predict the distance walked during 6MWT (6MWD) for healthy Singaporeans aged 21-80. This cross-sectional study recruited community-dwelling healthy subjects aged 21-80 via convenience sampling. Each subject completed two trials of 6MWT according to the standard protocol. Primary outcome measures included 6MWD, pre-and post-test heart rate (HR), oxygen saturation, and blood pressure (BP). 172 healthy Singaporeans (females=90, males=82) participated. The overall mean 6MWD was 578.00±75.38 metres. The age-stratified mean 6MWD ranged from 601.3±71.79 metres (aged 21-39) to 519.02±55.42 metres (aged 60-80). Age, gender, and percentage maximum HR predicted (%PredHRmax) were the most significant variables (p<0.001). 6MWD reference equation=288.282(height,m)+27.463×Gender (male=1;female=0)+4.349(%predHRmax)+1.191 (HR reserve, bpm) -185.431-1.343(age,years)-1.614 (weight, kg), R2=58%. Applying equations from other studies to the Singaporean population resulted in an overestimation of the 6MWD. This study updated the NRV and reference equations of 6MWD for healthy Singaporeans aged between 21-80 years. This update revises the local benchmarks of 6MWD in Singapore, a widely adopted outcome measure.


Results of a comparative in vitro study of Duromedics and Björk-Shiley monostrut mitral heart valve prostheses.
Two different mechanical heart valves with annulus diameters 21-29 mm, (five Björk-Shiley monostrut tilting disc valves and five Duromedics bileaflet valves) have been tested in pulsatile flow in the mitral position of a mock circulation. Reflux, pressure, and orifice area have been measured while cardiac output was varied between 2 and 6 1 min-1. Insufficiency, mean orifice area, discharge coefficient, and performance and efficiency indices have been calculated. Mean values of insufficiency for the Björk-Shiley monostrut valves varied between 4.8 and 17.2% while the corresponding values for the Duromedics valves were in the range 6.1-17.3%. Mean values for orifice areas of the Björk-Shiley monostrut valves increased with the larger valve sizes from 101.1 to 210.2 mm2; for the Duromedics valves the area range was 134.5-262.9 mm2. Because of the larger orifice areas the values of discharge coefficient and performance index for the Duromedic valves were higher than those for the Björk-Shiley monostrut valves. As the insufficiency of the two mechanical valves was similar, and the orifice area of the bileaflet valves was greater than that of the tilting disc valves, Duromedics valves gave higher valves for the efficiency index, which varied between 0.31 and 0.39; for Björk-Shiley monostrut valves the index varied between 0.24 and 0.28 under the same test conditions. This hydrodynamic in vitro comparison of mechanical heart valves showed that the Duromedics bileaflet valves were superior to the Björk-Shiley tilting disc valves.


Survey of possible insecticide resistance in body lice.
WHO inaugurated in 1953 a global survey of the susceptibility of the body lice to insecticides. The test used consisted, essentially, of treating a balbriggan type of cloth with dusting powder, placing the lice upon it, and assessing the mortality 24 hours later. The present paper describes the results of tests carried out in 37 countries. A significant resistance to DDT has been found to be present in many countries, and there are indications of several instances of BHC-resistance.


Preventability of venous thromboembolism in hospitalised patients.
Hospital-acquired venous thromboembolism (VTE) is a major cause of morbidity and mortality. To determine the proportion of patients with hospital-acquired VTE that are preventable. This was a retrospective study of patients in two tertiary care hospitals in Sydney, Australia. Data were collected for patients with hospital-acquired VTE based on International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Australian Modification (ICD-10-AM) coding from January 2018 to May 2020. Patients were classified as low, moderate or high risk of developing a VTE during hospitalisation based on demographic and clinical factors. A hospital-acquired VTE was considered to be potentially preventable if there was suboptimal prophylaxis in the absence of contraindications. Suboptimal therapy included at least one of the following related to VTE prophylaxis: low dose, missed dose (prior to developing a VTE), suboptimal drug and delayed start (>24 h from admission). There were 229 patients identified with VTE based on ICD-10-AM coding. A subset of 135 patients were determined to have actual hospital-acquired VTE. Of these, there were no patients at low risk, 64% (87/135) at moderate risk and 44% (48/135) at high risk of developing a VTE. Most (65%; n = 88/135) patients had one or more contraindications to receive recommended prophylaxis. Overall, the proportion of patients who received suboptimal prophylaxis was 11% (15/135). Approximately one out of 10 hospital-acquired VTE are preventable. Hospitals should focus on measuring and reporting VTE that are preventable to provide a more accurate measure of the burden of VTE that can be reduced by improving care.


A novel approach for the development of edible oleofoams using double network oleogelation systems.
Whipped oleogels (oleofoams) are commonly stabilized by crystalline particles. Still, external factors like temperature fluctuations could change the state of the crystals (phase transitions), leading to the destabilization and disruption of oleofoams. Herein, a double network oleogelation system comprised of a primary crystalline network (using glycerol monostearate) and a secondary colloidal network (stabilized by soy protein isolate-anionic polysaccharides Mailard conjugates) is proposed as a novel strategy to overcome these challenges. It was observed that the incorporation of the secondary network resulted in a lower over-run, but a higher melting point, elasticity, foam stability, and more uniform bubble size distribution. This was explained by the strong interfacial stabilization provided by the colloidal network that can protect the crystalline particle against coarsening and oil drainage. These double network oleofoams, which could retain 41-48 % air (oleogel-based), display great potential for utilization in low-calorie lipid-based products.


Transverse closure of mesenterico-portal vein after vein resection in pancreatoduodenectomy.
Resection of the involved mesenteric-portal vein (MPV) is increasingly performed in pancreatoduodenectomy. The primary aim of this study is to assess the rate of R0 resection in transverse closure (TC) versus segmental resection with end-to-end (EE) closure and the secondary aims are to assess the short-term morbidity and long-term survival of TC versus EE. Patients undergoing pancreatoduodenectomy with MPV resection were identified from a prospectively database. The reconstruction technique were examined and categorized. Clinical, pathological, short-term and long-term survival outcomes were compared between groups. 110 patients underwent PD with MPV resection of which reconstruction was performed with an end-to-end technique in 92 patients (84%) and transverse closure technique in 18 patients (16%). Patients undergoing transverse closure tended to have had a shorter segment of vein resected (≤2 cm) compared to the end-to-end (83% vs. 43%; P = 0.004) with no difference in R0 rate. Short-term morbidity was similar. The median and 5-year survival was 30.0 months and 18% respectively for patients undergoing transverse closure and 28.6 months and 7% respectively for patients undergoing end-to-end reconstruction (P = 0.766). Without compromising the R0 rate, transverse closure to reconstruct the mesenteric-portal vein is shown to be feasible and safe in the setting when a short segment of vein resection is required during pancreatoduodenectomy. Synopsis - We describe a vein closure technique, transverse closure, which avoids the need for a graft, or re-implantation of the splenic vein when resection of the mesenteric-portal vein confluence is required during pancreatoduodenectomy.


Visual processing of looming and time to contact throughout the visual field.
We measured discrimination threshold for time to contact with a simulated approaching object at 20 locations between 0 and 32 deg eccentricity in the left, right, upper, and lower visual fields. We also measured discrimination threshold for rate of expansion at the same 20 locations. At 0 deg eccentricity, discrimination of trial-to-trial variations in time to contact was virtually unaffected by simultaneous trial-to-trial variations of both rate of expansion and starting size, discrimination of trial-to-trial variations in rate of expansion was virtually unaffected by simultaneous trial-to-trial variations of both time to contact and starting size, and discrimination of trial-to-trial variations in starting size was virtually unaffected by simultaneous trial-to-trial variations of both time to contact and rate of expansion. We conclude that, in foveal vision, time to contact, rate of expansion and size can be processed simultaneously, independently and in parallel. Our main finding was that this independence progressively decreased as eccentricity increased. For example, in peripheral, but not in foveal vision, variations in rate of expansion produced illusory variations in time to contact. A secondary finding was that the effect of eccentricity on discrimination threshold for the task-relevant variable (whether time to contact or rate of expansion) was considerably less than the effect of eccentricity on visual acuity and on several other aspects of visual performance. We suggest that visual processing of time to contact is developed by exposure to optic flow patterns created by self-locomotion.


Humanities, criticality and transparency: global health histories and the foundations of inter-sectoral partnerships for the democratisation of knowledge.
Historians of medicine have been influential actors in a broader movement to highlight the social, institutional and administrative benefits of historical research, and its relevance for national and international policy intended to extend and improve contemporary healthcare. Historical perspectives are fundamentally useful to health policy actors because questions about what it is to be healthy, to suffer disease or disability, and the presentation and acceptance of solutions are interwoven in culturally and historically complex webs of meaning. Historians, as they have examined the social and cultural social determinants of health, have also used their work as public engagement, educational and policy resource tools, demonstrating that history is an effective way of making key issues in science, medicine and well-being more administratively responsive and accessible to lay audiences. This article explores such issues through the case study of the long-running World Health Organization (WHO) Global Health Histories project. Established in late 2004, the project's enduring rationale has been that understanding the history of health helps the global public health community to respond to the challenges of today and help shape a healthier future. It has sought to do this by bringing together researchers and policy-makers into honest and democratic conversations and exchanges of ideas. The aim has been to stimulate a fusion between historical evidence and current policy approaches to many of the most urgent health issues. This article discusses the challenges and opportunities in bringing health history and policy together, and explores the importance of explaining historical method and the need to convince policy partners how history is evidence-based, that it can access and provide useful strategic information from archives of major institutions, and, therefore, a useful contributor to making policy initiatives adaptable and acceptable within complex polities and societies.


Prevalence and influencing factors of the high nil-control spot count in T-SPOT.TB: A matched case-control study.
T-SPOT.TB may yield indeterminate results, including high nil responses and insufficient mitogen responses. We explored the incidence and risk factors of high nil responses. A 1:1 matched case-control study of patients who underwent T-SPOT.TB tests in Peking Union Medical College Hospital from Jan 1, 2015 to Apr 30, 2017 was conducted. High nil responses were defined as >10 spots in negative control wells. Cases and controls were matched based on when the tests were performed. Demographic, clinical and laboratory data were obtained from the Medical Record System. A total of 644 out of 36,316 (1.76%, 95% CI: 1.63%-1.90%) patients presented with high nil responses (280 cases and 280 controls were enrolled). Multivariate analysis revealed that male (OR = 1.882, 95% CI: 1.222-2.899), Behcet's disease (OR = 7.764, 95% CI: 1.714-35.167), heavy use of corticosteroids within a month (OR = 0.357, 95% CI: 0.138-0.921, for >1000 mg group) and hypoalbuminemia (OR = 0.385, 95% CI: 0.241-0.615) are significantly associated with high nil responses. High nil responses in T-SPOT.TB assays are quite rare. Male gender and Behcet's disease are suggested as independent risk factors, while recent excessive use of corticosteroids and hypoalbuminemia seem to be independent protective factors.


A 2019 reproductive update from the Midwest Reproductive Symposium International.
"Mystery, Medicine, and the Magnificent Mile," the theme for the annual Midwest Reproductive Symposium International (MRSi) in Chicago, IL, captured the attention of reproductive professionals all over the world. Each year, the conference agenda encompasses emerging technologies in assisted reproduction, updates in the management of reproductive diseases, and common challenges encountered in clinical practice. The structure of the meeting, offering a mixture of lectures, panel discussions, and interactive workshops, creates a collaborative environment for physicians, geneticists, embryologists, nurses, mental health professionals, basic scientists, business administrative professionals, reproductive endocrinology and infertility fellows, and obstetrics and gynecology residents. The goal of the MRSi meeting is to provide all reproductive professionals the opportunity to exchange ideas, foster relationships, and deliver quality patient care. As the field continues to evolve, MRSi provides an exciting venue to uncover the mysteries of reproductive medicine with enthusiasm and collaboration.


P2X7 receptor: the regulator of glioma tumor development and survival.
P2X7 is an ionotropic nucleotide receptor, forming the cation channel upon ATP stimulation. It can also function as a large membrane pore as well as transmit ATP-dependent signal without forming a channel at all. P2X7 activity in somatic cells is well-known, but remains poorly studied in glioma tumors. The current paper presents the comprehensive study of P2X7 activity in C6 and glioma cell line showing the wide range of effects the receptor has on glioma biology. We observed that P2X7 stimulation boosts glioma cell proliferation and increases cell viability. P2X7 activation promoted cell adhesion, mitochondria depolarization, and reactive oxygen species overproduction in C6 cells. P2X7 receptor also influenced glioma tumor growth in vivo via activation of pro-survival signaling pathways and ATP release. Treatment with Brilliant Blue G, a selective P2X7 antagonist, effectively inhibited glioma tumor development; decreased the expression of negative prognostic cancer markers pro-survival and epithelial-mesenchymal transition (EMT)-related proteins; and modulated the immune response toward glioma tumor in vivo. Finally, pathway-specific enrichment analysis of the microarray data from human patients also showed an upregulation of P2X7 receptor in gliomas from grades I to III. The presented results shed more light on the role of P2X7 receptor in the biology of this disease.


Incidence of squamous cell carcinoma in oral lichen planus: a 25-year population-based study.
Oral lichen planus (OLP) is a chronic inflammatory condition of the oral mucosa. Multiple studies have shown that approximately 1% of patients with OLP will develop oral squamous cell carcinoma (OSCC), however, no study has taken a population-based multicenter approach to demonstrate this association. Our main objective was to determine the incidence of OSCC in OLP in a specific population and secondarily to assist physicians regarding appropriate long-term monitoring of patients with OLP. We conducted a population-based retrospective cohort study. Patients with OLP from 1986 through 2010 were identified using the Rochester Epidemiology Project (REP) for Olmsted County, Minnesota. For each OLP case (n = 303), we randomly selected two age- and gender-matched referents (n = 606). OLP diagnosis was established based on the World Health Organization (WHO) criteria. Medical records were reviewed for development of OSCCafter the OLP diagnosis (index date). The association between OLP and development of OSCC was assessed. In total, 303 patients with incident OLP were identified; the overall incidence of OLP per 100,000 person-years was 11.4 (95% CI, 10.1-12.7). Among the OLP cohort, 7 had OSCC (incidence of OSCC, 3.1%; 95% CI, 0.6-6.4%) at 20 years after OLP diagnosis. Three OSCC cases were identified among the referents. Patients with OLP were 4.8 times more likely to have OSCC than the matched referents. The median time to OSCC development was 14.7 years earlier for the OLP cohort. Patients with OLP, particularly the erosive type, have an increased incidence of OSCC development and should be monitored closely.


Soft Tissue Injury in Preparation for Implants.
Diagnosis and treatment planning are critical in preparation for implant placement. Adequate evaluation, preoperative imaging, and surgical planning minimize early and late-stage soft tissue injuries. Correct placement of dental implants can be challenging with several contributing factors such as lack of proper preoperative soft tissue evaluation and surgical experience in dealing with soft tissue incisions and flap reflection, resulting in injury and complications involving the soft tissues.


Good responders to catheter ablation for long-standing persistent atrial fibrillation: Clinical and genetic characteristics.
Radiofrequency catheter ablation (RFCA) for long-standing persistent atrial fibrillation (L-PeAF) is challenging and has a relatively high recurrence rate. We explored clinical and genetic characteristics associated with being good responders (no early or clinical recurrence within 12 months in the absence of anti-arrhythmic drugs) to RFCA among patients with L-PeAF. Of 1319 patients in the Yonsei AF Ablation Cohort, this study included 141 consecutive patients with L-PeAF (80.9% male, age 57.8±9.7 years) who were followed >12 months after RFCA. During 25 (19-35) months follow-up, the recurrence rate was 39%, and 38 patients (27%) were categorized as good responders, those had a shorter AF duration (p=0.010), and smaller left atrial (LA) size (p=0.033) than others. The rs2106216 (16q22/ZFHX3) genetic polymorphism was independently associated with being a good responder in multivariate analysis (adjusted OR=2.70, 95% CI 1.41-5.14, p=0.003), after adjusting for LA size and AF duration. The rs2106261 had predictive value for clinical recurrence of AF after RFCA among patients with an AF duration 12-65 months (log rank, p=0.025). Despite a relatively high recurrence rate after RFCA for L-PeAF, patients with a shorter AF duration and smaller LA size showed a more favorable outcome. The rs2106216 polymorphism (ZFHX3) was independently associated with being good responders to RFCA for L-PeAF, especially with AF duration 12-65 months.


Assessment of local management practices on the population ecology of some medicinal plants in the coniferous forest of Northern Parts of Pakistan.
A study on the assessment of local management practices on the population of three medicinal plants viz.: Persicaria amplexicaule. D. Don., Valeriana jatamansi Jones and Viola serpens Wall ex Roxb was conducted during 2002-2004 in the coniferous forest of Northern Parts of Pakistan. The objective of the study was to know the impact of current management practices on the population size of targeted plants. The study showed that the involvement of locals in the gathering of targeted plants varied with the change in elevation. Among the targeted plants V. serpens was collected by large majorities of people (83.3%) at 2700 m followed by 72% at 2300 m and 37% at 1900 m. V. jatamansi was harvested by a small number of people (18.1%) at 1900 and 2300 m each, followed by 8.3% at 2700 m. While P. amplexicaule was harvested by a few collectors (9.1%) at 1900 m and 9.6% at 2300 m followed by 8.3% at 2700 m. The study concluded that these species have been extracted so heavily in the past that they are found now sparsely in some sites of the study area. Secondly, due to loss of its habitat by deforestation and encroachment of land for cultivation its population is on the decline towards extinction. Therefore, the current study recommends the conservation of the remaining populations of targeted plants through active participation of local communities.


Digital breast tomosynthesis versus digital mammography: integration of image modalities enhances deep learning-based breast mass classification.
To evaluate the impact of utilizing digital breast tomosynthesis (DBT) or/and full-field digital mammography (FFDM), and different transfer learning strategies on deep convolutional neural network (DCNN)-based mass classification for breast cancer. We retrospectively collected 441 patients with both DBT and FFDM on which regions of interest (ROIs) covering the malignant, benign and normal tissues were extracted for DCNN training and validation. Experiments were conducted for tasks in distinguishing malignant/benign/normal: (1) classification capabilities of DBT vs FFDM and the role of transfer learning were validated on 2D-DCNN; (2) different strategies of combining DBT and FFDM and the associated impacts on classification were explored; (3) 2D-DCNN and 3D-DCNN trained from scratch with volumetric DBT were compared. 2D-DCNN with transfer learning outperformed that without for DBT in distinguishing malignant (ΔAUC = 0.059 ± 0.009, p < 0.001), benign (ΔAUC = 0.095 ± 0.010, p < 0.001) and normal tissue (ΔAUC = 0.042 ± 0.004, p < 0.001) (paired samples t test). 2D-DCNN trained on DBT (with transfer learning) achieved higher accuracy than those on FFDM (malignant: ΔAUC = 0.014 ± 0.014, p = 0.037; benign: ΔAUC = 0.031 ± 0.006, p < 0.001; normal: ΔAUC = 0.017 ± 0.004, p < 0.001) (independent samples t test). The 2D-DCNN employing both DBT and FFDM for training achieved better performances in benign (FFDM: ΔAUC = 0.010 ± 0.008, p < 0.001; DBT: ΔAUC = 0.009 ± 0.005, p < 0.001) and normal (FFDM: ΔAUC = 0.005 ± 0.003, p < 0.001; DBT: ΔAUC = 0.002 ± 0.002, p < 0.001) (related samples Friedman test). The 3D-DCNN and 2D-DCNN trained from scratch with DBT only produced moderate classification. Transfer learning facilitates mass classification for both DBT and FFDM, and DBT outperforms FFDM when equipped with transfer learning. Integrating DBT and FFDM in DCNN training enhances mass classification accuracy for breast cancer. • Transfer learning facilitates mass classification for both DBT and FFDM, and the DBT-based DCNN outperforms the FFDM-based DCNN when equipped with transfer learning. • Integrating DBT and FFDM in DCNN training enhances breast mass classification accuracy. • 3D-DCNN/2D-DCNN trained from scratch with volumetric DBT but without transfer learning only produce moderate mass classification result.


Choice based on exclusion in pigeons.
When humans acquire a conditional discrimination and are given a novel-sample-comparison choice, they often reject a comparison known to be associated with a different sample and choose the alternative comparison by default (or by exclusion). In Experiment 1, we found that if, following matching training, we replaced both of the samples, acquisition took five times longer than if we replaced only one of the samples. Apparently, the opportunity to reject one of the comparisons facilitated the association of the other sample with the remaining comparison. In Experiment 2, we first trained pigeons to treat two samples differently (to associate Sample A with Comparison 1 and Sample B with Comparison 2) and then trained them to associate one of those samples with a new comparison (e.g., Sample A with Comparison 3) and to associate a novel sample (Sample C) with a different, new comparison (Comparison 4). When Sample B then replaced Sample C, the pigeons showed a significant tendency to choose Comparison 4 over Comparison 3. Thus, when given the opportunity, pigeons will choose by exclusion.


Effect of lesion of the nucleus basalis of rat on acetylcholine release in cerebral cortex: time course of compensatory events.
Excitotoxin lesion of the nucleus basalis of the rat causes a substantial reduction in the K+-evoked release of [3H]acetylcholine (ACh) from tissue slices of ipsilateral frontal and parietal cortex. Decreases in the K+-evoked release of [3H]ACh (nCi/mg protein) of 71% and 47% are seen 21 days after lesion in the frontal and parietal cortex respectively. However, in later periods a considerable reversal of this deficit occurred which was complete in parietal cortex at 102 days, when the K+-evoked release of [3H]ACh was not significantly different from the controls. In the frontal cortex where a greater decrease in acetylcholinesterase (AChE) is obtained, a similar but attenuated reversal occurred, the K+-evoked release of [3H]ACh reaching 75% of the control value at 128 days after lesion. The compensatory changes in [3H]ACh release were paralleled by changes in AChE in both regions. Despite the reduced level of release following lesion, the K+-evoked release of [3H]ACh was responsive to the inhibitory effect of the cholinergic agonist, oxotremorine. Lesions outside the nucleus basalis produced no changes in the release of [3H]ACh from frontal or parietal cortex. All lesions were verified histologically. The compensatory changes reported are discussed in terms of the growth of 'sprouts' from the spared cholinergic axons. This study clearly demonstrates that compensatory changes in complex systems such as transmitter release which markedly affect cholinergic function do occur in response to lesion in common with other presynaptic parameters.


Binding characteristics and apparent molecular size of detergent solubilized nerve growth factor receptor of sympathetic ganglia.
Nerve growth factor (NGF), a hormone-like regulator of sympathetic neuron ontogeny and metabolism affects its target cells initially by associating with specific plasma membrane receptors. We have solubilized the NGF receptor of adult rabbit superior cervical ganglia (SCG) with the nonionic detergent Triton X-100. The high-affinity equilibrium binding constant of the detergent-extracted receptor is 2-8 x 10(-10) M. Gel chromatography of the receptor or the 125I-labeled NGF receptor complex on a column of Sepharose 6B indicated, in both cases, a single component of an apparent hydrodynamic radius of 71 +/- 5 A. In parallel investigations, we have confirmed the similarity between the hydrodynamic size of the NGF receptor of rabbit SCG and that of the insulin receptor of IM-9 lymphocytes evaluated by similar methods.


Reviewing hypothetical migraine studies using funding criteria from the Patient-Centered Outcomes Research Institute.
What role can rigorous observational comparative effectiveness studies play in guiding clinical decision making? What criteria should be used in determining whether the results of such studies should be communicated to clinicians and to patients? We address these questions by considering two hypothetical observational studies in patients with migraine against the backdrop of the review criteria drawn up by the Patient-Centered Outcomes Research Institute (PCORI). These criteria emphasize that patient-centered comparative effectiveness research should exhibit relevance to patients, have great potential to affect practice and improve outcomes, and be conducted using rigorous analytic methods. We conclude that these hypothetical studies would be unlikely to have been funded or communicated by PCORI, and we offer suggestions for improving their relevance and analytic approaches. We also conclude that high-quality observational studies can effectively complement findings from randomized trials, and that communicating their results to patients and clinicians is warranted.


[Effects of Panax notoginseng saponins on rat cardiomyocytes apoptosis induced by angiotengin II in vitro].
To study the protective effects of Panax notoginseng saponins (PNS) on angiotensin II (Ang II)-induced rat cardiomyocyte apoptosis in vitro and the probable mechanism. Cultured cardiomyocytes from neonatal rats were stimulated with Ang II. Cell viability was measured by MTT. Apoptosis was evaluated using Acridine Orange (AO) fluorescent dye staining and flow cytometry; Fluo-3 AM was used to test the change of intracellular free calcium. It was found that incubating with Ang II (10(-7) mol x L(-1)) for 48 h increased cardiomyocyte apoptosis, PNS (25, 100 mg x mL(-1)) increased myocyte viability. PNS (50 mg x mL(-1)) significantly decreased this Ang II-induced rat cardiomyocyte apoptosis (P < 0.05) and decreased fluorescent intensity of intracellular calcium. PNS has a significant effect on Ang II-induced rat cardiomyocytes apoptosis in vitro by alleviating intracellular calcium overload.


Gene-independent therapeutic interventions to maintain and restore light sensitivity in degenerating photoreceptors.
Neurodegenerative retinal diseases are a prime cause of blindness in industrialized countries. In many cases, there are no therapeutic treatments, although they are essential to improve patients' quality of life. A set of disease-causing genes, which primarily affect photoreceptors, has already been identified and is of major interest for developing gene therapies. Nevertheless, depending on the nature and the state of the disease, gene-independent strategies are needed. Various strategies to halt disease progression or maintain function of the retina are under research. These therapeutic interventions include neuroprotection, direct reprogramming of affected photoreceptors, the application of non-coding RNAs, the generation of artificial photoreceptors by optogenetics and cell replacement strategies. During recent years, major breakthroughs have been made such as the first optogenetic application to a blind patient whose visual function partially recovered by targeting retinal ganglion cells. Also, RPE cell transplantation therapies are under clinical investigation and show great promise to improve visual function in blind patients. These cells are generated from human stem cells. Similar therapies for replacing photoreceptors are extensively tested in pre-clinical models. This marks just the start of promising new cures taking advantage of developments in the areas of genetic engineering, optogenetics, and stem-cell research. In this review, we present the recent therapeutic advances of gene-independent approaches that are currently under clinical evaluation. Our main focus is on photoreceptors as these sensory cells are highly vulnerable to degenerative diseases, and are crucial for light detection.


Discovery of a novel restriction endonuclease by genome comparison and application of a wheat-germ-based cell-free translation assay: PabI (5'-GTA/C) from the hyperthermophilic archaeon Pyrococcus abyssi.
To search for restriction endonucleases, we used a novel plant-based cell-free translation procedure that bypasses the toxicity of these enzymes. To identify candidate genes, the related genomes of the hyperthermophilic archaea Pyrococcus abyssi and Pyrococcus horikoshii were compared. In line with the selfish mobile gene hypothesis for restriction-modification systems, apparent genome rearrangement around putative restriction genes served as a selecting criterion. Several candidate restriction genes were identified and then amplified in such a way that they were removed from their own translation signal. During their cloning into a plasmid, the genes became connected with a plant translation signal. After in vitro transcription by T7 RNA polymerase, the mRNAs were separated from the template DNA and translated in a wheat-germ-based cell-free protein synthesis system. The resulting solution could be directly assayed for restriction activity. We identified two deoxyribonucleases. The novel enzyme was denoted as PabI, purified and found to recognize 5'-GTAC and leave a 3'-TA overhang (5'-GTA/C), a novel restriction enzyme-generated terminus. PabI is active up to 90 degrees C and optimally active at a pH of around 6 and in NaCl concentrations ranging from 100 to 200 mM. We predict that it has a novel 3D structure.


The dynamics of leaf extension in plants with diverse altitudinal ranges : II. Field studies in Poa species between 600 and 3200 m altitude.
The dynamics of leaf extension in five species of Poa were studied with electronic auxanometers (LVDTs) along an elevational gradient from 600 to 3200 m in the Austrian Alps. Extension rates peak at midday at all elevations and rates at 20°C are almost twice as high at low elevation as compared with those from the highest sites. The low temperature threshold for leaf extension drops by 7 K over this range of elevation, with plants from the highest sites showing some extension around freezing point. Thus, there is a substantial adaptive adjustment in response of leaf extension to declining mean temperatures with increasing altitude, which is not paralleled by known altitudinal trends of photosynthetic responses in herbaceous plants.


The utility of using Volunteered Geographic Information (VGI) for evaluating pluvial flood models.
Pluvial floods are increasingly threatening urban environments worldwide due to human-induced climate change. High-resolution, state-of-the-art pluvial flood models are urgently needed to inform climate change adaptation and disaster risk reduction measures but are generally not empirically tested because of the rarity of local high-intensity precipitation events and the lack of monitoring capabilities. Volunteered Geographic Information (VGI) collected by professionals, non-professionals and citizens and made available on the internet can be used to monitor the dynamic extent of a pluvial flood during and after an extreme rain event but is sometimes considered to be unreliable. In this paper, we explore the general utility of VGI to evaluate the performance of pluvial flood models and gain new insights to improve these models. As background for our research, we use the capital city of Budapest, which recently suffered three heavy rainfall events in just five years (2015, 2017 and 2020). For each pluvial flood event, we collected photographic evidence from different online media sources and estimated the associated water depths at various locations in the city from the image context. These were compared with the results of a 2D pluvial flood model that has been shown to provide comparable results to other state-of-the-art inundation models and is easily transferred to other urban areas due to its reliance on open data sources. We introduce a general methodology for comparing VGI with model data by probing different spatial resolutions. Our findings highlight untapped potential and fundamental challenges in using VGI for model evaluation. It is proposed that VGI may become an essential tool and improve the confidence in model-based risk assessments for climate change adaptation and disaster risk reduction.


Meta-Synthesis of the Needs of Women Cared for by Midwives During Childbirth in Hospitals.
To identify and meta-synthesize results of qualitative studies on the needs of women cared for by midwives during childbirth in hospitals. MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, and the Cochrane Library. We restricted the bibliographic search to articles published in English to July 31, 2020. The initial search yielded 6,407 articles, and after 2,504 duplicates were removed, we screened the titles and abstracts of 3,903 articles. We conducted a full-text review of 89 articles and included 13 qualitative studies about the needs of women who were hospitalized during childbirth and had midwives as their primary maternity care providers. We extracted data (e.g., authors, publication date, type of study, sample size, results, and quotes) from the full text of each article into a standardized table. Two authors reviewed all articles using the Critical Appraisal Skills Programme tool to assess study quality and to independently score each study. We analyzed the findings of each study and synthesized them to develop themes. We found 14 major themes that reflected the needs of women during hospitalization for childbirth: Nutrition, Hygiene, Privacy, Information, Bodily Respect, Respect for Social Role, Family Intimacy, Shelter, Pain Management, Partnership, Movement, Reassurance, Support, and Empowerment. We categorized these themes in Maslow's hierarchy of needs to better understand the phenomenon. We identified 14 needs that midwives and nurses can meet when they care for women in hospitals during childbirth. Standardized methods to assess these needs and to link them to specific interventions can be used by midwives and nurses, which will likely affect women's satisfaction with their experience and overall quality of care.


Constituents from leaves of Quillaja brasiliensis.
A new abietane diterpene, the 19-O-beta-D-glucopyranoside of 16-hydroxylambertic acid was isolated from the leaves of Quillaja brasiliensis together with a known prosapogenin (3-O-beta-D-glucuronopyranosyl-quillaic acid), quercetin, and rutin. The new compound was identified by chemical and spectroscopic methods.


PCR-fingerprinting for selection of HLA matched unrelated marrow donors. Collaborating Centres in the IMUST Study.
HLA typing contributes to the delays that occur in the search for HLA-matched unrelated marrow donors, and that result in poor patient survival. A new DNA technique for testing DR match between patient and unrelated marrow donors has been assessed. The technique is based on the formation of heteroduplexes between heterologous amplified coding and non-coding DNA sequences during the final annealing stage of the polymerase chain reaction (PCR), and different HLA-DR/Dw types give unique banding patterns ("PCR fingerprints") on non-denaturing polyacrylamide gel electrophoresis. HLA-DR matching is by visual comparison of patients' with donors' fingerprints. Identity can be confirmed by mixing donor and recipient DNA before the final stage of the PCR ("DNA crossmatching"). In an assessment of the technique in 53 unrelated HLA-A and HLA-B matched patient-donor pairs, 42 pairs gave the same results with PCR fingerprinting as with DNA-RFLP analysis. In the 11 other pairs DR/Dw mismatches were detected by PCR fingerprinting but not by the standard DNA-RFLP method; PCR-SSO typing with selected sequence-specific oligonucleotides (SSO) confirmed that mismatches were due to different subtypes of DR4. PCR fingerprinting might thus accelerate the selection of unrelated marrow donors by simplifying the logistics of the donor search.


Depression in medically ill patients.
In medically ill patients, given the many entities the phenotype of depression may represent, clinicians must be prepared to cast their diagnostic nets widely, not settling for the obvious but frequently incorrect choice of major depressive episode and throwing antidepressants at it willy nilly. Having chosen the correct diagnosis from among a broad differential of depression "look-alikes," clinicians can draw upon a broad swath of treatment modalities including medications, psychotherapy, social supports, and spiritual interventions. Working as a psychiatrist in the medical arena requires the curiosity and analytic skills of a detective and the breadth of knowledge of a polymath adapting therapeutic tools from across the biopsychosociospiritual spectrum to the specific needs of the patient.


The assembly of protein subunits and cofactors in photosystem I.
The recently determined crystal structures of photosystems I and II at 2.5 A and 3.8 A resolution, respectively, have improved the structural basis for understanding the processes of light trapping, exciton transfer and electron transfer occurring in the primary steps of oxygenic photosynthesis. Understanding the assembly of the 12 protein subunits and 128 cofactors in photosystem I allows us to study the possible functions of the individual players in this protein-cofactor complex.


Design, Synthesis and Biological Evaluation of Novel Substituted N,N'-Diaryl ureas as Potent p38 Inhibitors.
A novel series of substituted N,N'-diaryl ureas that act as p38α inhibitors have been designed and synthesized based on two key residues (Gly110 and Thr106) that are different in p38α MAPK than in other kinases. Preliminary biological evaluation indicated that most compounds possessed good p38α inhibitory potencies. Among these compounds, 9g appeared to be the most powerful and is the main compound that we will study in the future.


Monitoring of low dabigatran concentrations: diagnostic performance at clinically relevant decision thresholds.
The direct oral anticoagulant dabigatran does not require therapeutic drug monitoring, however emergency measurements are gaining importance. Current assays feature good performance at intermediate and high dabigatran concentrations but show limited accuracy at low concentrations. This area requires more attention as clinical decision threshold values currently lie at 30 and 50 ng/ml. The objective of the study was to evaluate and compare diagnostic performance of dabigatran assays at these thresholds. Dabigatran concentrations of 293 plasma samples taken from 50 patients were measured with the INNOVANCE direct thrombin inhibitor assay (DTI) from Siemens, the Biophen direct thrombin inhibitor assay (BDTI), the BDTI using a low range calibrator (BDTI-low), the Hemoclot direct thrombin inhibitor assay (HTI) and an ecarin clotting time assay (ECT). Assay results were compared to ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and test characteristics were calculated for thresholds of 30 and 50 ng/ml. DTI, BDTI-low and ECT showed very strong correlation and high agreement with UPLC-MS/MS and an improved determination of low dabigatran concentrations. ROC curve analyses revealed very high accuracy at the 30/50 ng/ml thresholds for DTI (AUC = 0.989/0.995), BDTI-low (AUC = 0.980/0.991) and ECT (AUC = 0.990/0.996) measurements. Sensitivity and specificity in detecting were calculated for DTI (98/92%), BDTI-low (87/95%), ECT (97/96%), BDTI (99/82%) and HTI (86/89%) measurements. Compared to the previously available HTI and BDTI, both novel assays, DTI and BDTI-low, reliably determine low dabigatran plasma concentrations around the clinical decision thresholds with very high sensitivity and specificity.


Electrotransfer of the epinecidin-1 gene into skeletal muscle enhances the antibacterial and immunomodulatory functions of a marine fish, grouper (Epinephelus coioides).
Electrotransfer of plasmid DNA into skeletal muscle is a common non-viral delivery system for the study of gene function and for gene therapy. However, the effects of epinecidin-1 (epi) on bacterial growth and immune system modulation following its electrotransfer into the muscle of grouper (Epinephelus coioides), a marine fish species, have not been addressed. In this study, pCMV-gfp-epi plasmid was electroporated into grouper muscle, and its effect on subsequent infection with Vibrio vulnificus was examined. Over-expression of epi efficiently reduced bacterial numbers at 24 and 48 h after infection, and augmented the expression of immune-related genes in muscle and liver, inducing a moderate innate immune response associated with pro-inflammatory infiltration. Furthermore, electroporation of pCMV-gfp-epi plasmid without V. vulnificus infection induced moderate expression of certain immune-related genes, particularly innate immune genes. These data suggest that electroporation-mediated gene transfer of epi into the muscle of grouper may hold potential as an antimicrobial therapy for pathogen infection in marine fish.


Clinicopathological characteristics of placental chorioangioma: A clinicopathological study of 77 cases.
To explore clinicopathological characteristics, diagnosis, differential diagnoses, treatment, and prognoses of placental chorioangioma (PCA). Placenta of 77 cases of PCA firmly diagnosed by pathology from 2009 through 2019 were collected, and clinicopathological characteristics of the patients were retrospectively analyzed. Seventy-seven patients were 20-41 (mean age, 28.8) years old at onset. Thirty patients showed pregnancy comorbidity. In one patient with the largest tumor (diameter, 16 cm), intrauterine fetal demise occurred at 33 weeks of gestation. Tumors were macroscopically manifested. The placental fetal surface showed a raised dark red to a pale pink nodule, quasi-round, with a maximum diameter of 0.2-16 cm. Microscopically, the tumors had a lot of capillaries and some interstitial loose connective tissue. One case was of atypical cellular chorioangioma. Immunophenotypically, CD34 (+) and Ki-67 proliferation indexes were less than 10%. Large PCA often accompanies pregnancy comorbidity. Atypical cellular chorangioma is rare and may be misdiagnosed as a malignant tumor. Therefore, improvement of understanding of such tumors can provide a basis for clinical diagnosis and intervention.


Echocardiographic findings and abnormalities in HIV-infected patients: results from a large, prospective, multicenter HIV-heart study.
The aim of the current study was to assess cardiac structure and function as well as cardiac abnormalities in a large patient-population based multicenter study of HIV-infected subjects. We enrolled 803 HIV-positive adults (83.4% men, mean age: 44.2 ± 10.3 yrs) in this prospective, cross-sectional cohort study. The study protocol included a standardized documentation of patient history, medical treatment and clinical examination. All subjects underwent a standardized transthoracic echocardiographic examination protocol including Doppler and tissue Doppler imaging. Echocardiographic measurements revealed a structural dilatation of the left ventricle in 10.1% of all HIV-infected subjects. Interventricular septum and posterior wall thickness were increased in 18.0% and 11.1%, respectively, with elevated muscle mass in 14.3% male and 19.4% female patients. Of all participants 13.5% exhibited a pathologic contraction characteristic of one or more myocardial segments. Prevalence of systolic and diastolic dysfunction was 34.3% and 48.0%, respectively. However, severe forms of ventricular dysfunction were rare. In conclusion our results demonstrate the relevance of echocardiography in this patient-population in the era of antiretroviral therapy. Above all, left ventricular wall thickness and function should be controlled regularly in HIV-infected subjects. (ClinicalTrials.gov number, NCT01119729).


Differential effects of D-Ala2 analogues of enkephalins on substance P-induced analgesia in rodents.
The systemic administration of subanalgesic doses of [D-Ala2, D-Leu5]enkephalin significantly potentiated the analgesia elicited in rats or mice by intraventricular injection of substance P. On the contrary, systemic administration of low doses of [D-Ala2,Met5]enkephalinamide antagonized the substance P-induced analgesia. The results support the notion of different physiological functions for the enkephalins and suggest an integrated role for enkephalins and substance P in the control of pain at supraspinal levels.


Glucose inhibits myo-inositol uptake and reduces myo-inositol content in cultured rat glomerular mesangial cells.
Although activation of polyol pathway has been proposed as one of the etiologic factors of diabetic complications, precise mechanism of the effect of polyol accumulation is still unclear. In order to test the hypothesis that there is an association of polyol pathway with myo-inositol metabolism, we measured myo-inositol content in cultured rat glomerular mesangial cells. By exposing the cells to high concentrations of glucose, intracellular myo-inositol content was reduced from 12.39 +/- 0.64 nmol/mg protein at 0 mmol/L glucose to 6.54 +/- 0.38 nmol/mg protein at 27.5 mmol/L glucose and 4.88 +/- 0.43 nmol/mg protein at 55 mmol/L glucose. This decrease of myo-inositol content was partially prevented by co-incubation with aldose reductase inhibitor, sorbinil. To examine further the mechanism of myo-inositol depletion, myo-inositol uptake by mesangial cells was studied. Major myo-inositol uptake process was sodium-dependent, saturable, and ouabain sensitive with Vmax of 171 pmol/mg protein/20 min and Km of 33 mumol/L. Sodium-dependent myo-inositol uptake was significantly inhibited by glucose in a dose-dependent manner only when glucose was present during uptake experiment, and kinetic analysis revealed the inhibition was competitive. Aldose reductase inhibition failed to prevent inhibitory effect of glucose on myo-inositol uptake. These data suggest that myo-inositol content of glomerular mesangial cells, which is reduced by high concentrations of glucose, is maintained by two processes: a glucose-sensitive but sorbitol-insensitive process, sodium-dependent myo-inositol uptake; and a sorbitol (aldose reductase) sensitive process, myo-Inositol depletion under high glucose condition may induce dysfunction of mesangial cells seen in diabetes.


RHOA takes the RHOad less traveled to cancer.
RAS and RHO GTPases function as signaling nodes that regulate diverse cellular processes. Whereas RAS mutations were identified in human cancers nearly four decades ago, only recently have mutations in two RHO GTPases, RAC1 and RHOA, been identified in cancer. RAS mutations are found in a diverse spectrum of human cancer types. By contrast, RAC1 and RHOA mutations are associated with distinct and restricted cancer types. Despite a conservation of RAS and RAC1 residues that comprise mutational hotspots, RHOA mutations comprise highly divergent hotspots. Whereas RAS and RAC1 act as oncogenes, RHOA may act as both an oncogene and a tumor suppressor. Thus, while RAS and RHO each take different mutational paths, they arrive at the same biological destination as cancer drivers.


Mortality in very preterm and very low birth weight infants according to place of birth and level of care: results of a national collaborative survey of preterm and very low birth weight infants in The Netherlands.
As part of a collaborative project in the Netherlands in 1983, for which data were collected on 1,338 newborn infants (less than 32 weeks' gestation and/or less than 1,500 g birth weight), all infants were assigned to one of three levels of care according to hospital of birth. Considerable centralization was achieved by antenatal and neonatal transport. Although the uncorrected mortality rates were similar, the mortality odds (adjusted for four and 22 potential confounding perinatal factors, respectively) were significantly higher in level 1 and level 2 hospitals compared with level 3 hospitals (tertiary perinatal care centers). By extending the facilities for full perinatal intensive care in level 3 centers and thus providing optimal care for all such infants, the overall mortality rate is expected to decrease further.


Intracaval and intracardiac leiomyomatosis of uterine origin.
Intracaval leiomyomatosis of uterine origin is a rare disease. Extension to the right heart is exceptional. Based on the review of 11 cases reported in the literature and the case presented herein, which was treated successfully, the diagnostic and therapeutic problems are discussed. Diagnosis should be suggested when a female patient operated on previously for myofibroma of the uterus by hysterectomy, presents with a picture of cardiac myxoma. Diagnosis can be confirmed by iliocavogram and computerized tomography of the abdomen. Excision calls for a cardiac procedure under extracorporeal circulation and caval exploration which may be performed either simultaneously or as a two stage procedure.


Organic aciduria and butyryl CoA dehydrogenase deficiency in BALB/cByJ mice.
A metabolic screening program of inbred strains of mice has detected a marked organic aciduria in the BALB/cByJ strain. Gas chromatographic and mass spectrometric analysis identified large quantities of n-butyrylglycine plus lesser quantities of ethylmalonic acid. Crosses with the nonexcreting C57BL/6J strain indicate that this condition is inherited as an autosomal recessive trait. Independently from this screening a variant with no detectable enzyme activity of butyryl CoA dehydrogenase (BCD) in liver and kidney of the BALB/cByJ strain but not other BALB/c sublines was discovered. Data from a three-point cross indicated that the null variant maps to the structural locus for the enzyme, Bcd-1, on chromosome 5. The findings indicate that a mutation at or near Bcd-1 in the BALB/cByJ strain resulted in a biochemical abnormality manifest as the BCD deficiency. It is concluded that accumulation of butyryl CoA due to a block in the oxidation of short-chain fatty acids results in an overproduction of organic metabolites leading to the observed organic aciduria. The fact that other BALB/c substrains do not exhibit this abnormality further suggests that this disorder reflects subline divergence within the BALB/c family.


Hepatitis C and hepatitis B virus infection: epidemiology and risk factors in a large cohort of pregnant women in Lorestan, West of Iran.
There are little data on the prevalence of serological markers of hepatitis B and hepatitis C viruses in pregnant women in Iran. This study was designed to determine the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection among pregnant women in Lorestan, west of Iran. Serum samples of 827 pregnant women who lived in rural (36.8%) and urban areas (63.2%) of Lorestan were collected during 2007-2008. Data were obtained through questionnaires. Samples were first screened for anti-HCV and anti-HBc by ELISA. Those who were positive for anti-HBc were tested for HBsAg. Anti-HBc was found in 28 of 827 pregnant women (overall prevalence, 3.4%; 14 of 523 in urban areas, 2.7%; 14 of 304 in rural areas, 4.6%). Of the 28 positive samples, 6(0.7%) were positive for HBs-Ag. Only 2 samples (0.2%) were anti-HCV-positive. These results underscore the need for prenatal screening for HBV infection in pregnant women and treatment of newborns from HBsAg-positive mothers.More studies are needed to identify risk factors of HCV infection and highlight the importance of HCV screening and treatment programs.


Development of mathematical models for an in vitro-phagocytosis test system.
Phagocytosis tests have been carried out by many authors using different methods under different conditions. The results have been interpreted in different ways, as well sometimes with conflicting notations. In order to get to a more systematic data analysis and to separate intrinsic from methodic influences, the possibility to apply mathematical models to a phagocytosis test has been studied. In agreement with previous experiences that phagocytosis can well be represented by a mathematical treatment as Michaelis-Menten-type enzyme kinetics concerning its initial rate and by an exponential function under in vivo conditions, in vitro-phagocytosis was phenomenologically described as an analogon of an irreversible bimolecular chemical reaction. In this way, rate and capacity of phagocytosis may be quantified separately. On the basis of systematic deviations of the data from this model, modifications have been developed which could be connected with pertinent observations. The design of further experiments from preliminary results on the basis of our models is discussed.


Effect of intraatrial reentry on initiation of atrioventricular reentrant tachycardia.
We studied the effect of intraatrial reentry (IAR) on initiation of orthodromic reentrant tachycardia (ORT) in 150 patients with Wolff-Parkinson-White syndrome using His-bundle recording and the atrial extrastimulus technique. IAR was initiated by premature atrial stimulation in 44 patients (29%), and it was followed by ORT in 16 patients (11%). In 8 patients (5%), IAR promoted the initiation of ORT, whereas in 5 patients (3%), IAR inhibited the initiation of ORT. These findings suggest that ORT is frequently induced following IAR. IAR, which was frequently observed during electrophysiological studies, seems to play an important role in the initiation of ORT.


Paralytic tremor (pt) rabbit: a sex-linked mutation affecting proteolipid protein-gene expression.
Paralytic tremor (pt) is a neurological sex-linked recessive mutation in rabbits which is characterized by a coarse body tremor and limb paresis. Morphological studies showed that this mutation affects CNS myelination. Although the number of oligodendrocytes is not reduced, myelination is slower, irregular and defective. We have made a biochemical and molecular analysis of 4-wk-old mutant and normal rabbits. The amount of myelin in the mutant represents only approximately 25% of the normal level. Radioimmunoassay for myelin basic protein showed a reduction to approximately 40% in pt whole-brain homogenate but the difference was not significant in purified myelin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of brain homogenates followed by immunoblotting showed that all major myelin proteins are affected by the pt mutation, although to different degrees. While most of the myelin proteins are reduced to approximately 60-80% of the normal level, an important reduction to approximately 30%, was measured for the proteolipid protein (PLP). In purified myelin, the difference in PLP concentration was significant while the other specific proteins were less affected. A similar reduction in myelin-protein gene expression was detected at the mRNA level. Sex-linked transmission, low concentrations of PLP and its specific mRNA in the CNS indicate that the pt mutation primarily affects the expression of the Plp gene.


Effect of continuous light and darkness on the testicular histology of toad (Bufo melanostictus).
Continuous darkness decreases spermatogenesis as well as Leydig cell function whereas continuous illumination suppresses spermatogenesis along with increased Leydig cell activity.


11-Cl-BBQ, a select modulator of AhR-regulated transcription, suppresses lung cancer cell growth via activation of p53 and p27Kip1.
Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and functions as a tumour suppressor in different cancer models. In the present study, we report detailed characterization of 11-chloro-7H-benzimidazo[2,1-a]benzo[de]iso-quinolin-7-one (11-Cl-BBQ) as a select modulator of AhR-regulated transcription (SMAhRT) with anti-cancer actions. Treatment of lung cancer cells with 11-Cl-BBQ induced potent and sustained AhR-dependent anti-proliferative effects by promoting G1 phase cell cycle arrest. Investigation of 11-Cl-BBQ-induced transcription in H460 cells with or without the AhR expression by RNA-sequencing revealed activation of p53 signalling. In addition, 11-Cl-BBQ suppressed multiple pathways involved in DNA replication and increased expression of cyclin-dependent kinase inhibitors, including p27Kip1 , in an AhR-dependent manner. CRISPR/Cas9 knockout of individual genes revealed the requirement for both p53 and p27Kip1 for the AhR-mediated anti-proliferative effects. Our results identify 11-Cl-BBQ as a potential lung cancer therapeutic, highlight the feasibility of targeting AhR and provide important mechanistic insights into AhR-mediated-anticancer actions.


Late Greenfield filter vena cava perforation causing a small bowel obstruction: case report.
This report describes a symptomatic case of vena caval perforation caused by a vena cava filter. Functional small bowel obstruction due to vascular compromise was caused by a prong of the filter.


CUL4B negatively regulates Toll-like receptor-triggered proinflammatory responses by repressing Pten transcription.
Toll-like receptors (TLRs) play critical roles in innate immunity and inflammation. The molecular mechanisms by which TLR signaling is fine-tuned remain to be completely elucidated. Cullin 4B (CUL4B), which assembles the CUL4B-RING E3 ligase complex (CRL4B), has been shown to regulate diverse developmental and physiological processes by catalyzing monoubiquitination for histone modification or polyubiquitination for proteasomal degradation. Here, we identified the role of CUL4B as an intrinsic negative regulator of the TLR-triggered inflammatory response. Deletion of CUL4B in macrophages increased the production of proinflammatory cytokines and decreased anti-inflammatory cytokine IL-10 production in response to pathogens that activate TLR3, TLR4, or TLR2. Myeloid cell-specific Cul4b knockout mice were more susceptible to septic shock when challenged with lipopolysaccharide, polyinosinic-polycytidylic acid or Salmonella typhimurium infection. We further demonstrated that enhanced TLR-induced inflammatory responses in the absence of CUL4B were mediated by increased GSK3β activity. Suppression of GSK3β activity efficiently blocked the TLR-triggered increase in proinflammatory cytokine production and attenuated TLR-triggered death in Cul4b mutant mice. Mechanistically, CUL4B was found to negatively regulate TLR-triggered signaling by epigenetically repressing the transcription of Pten, thus maintaining the anti-inflammatory PI3K-AKT-GSK3β pathway. The upregulation of PTEN caused by CUL4B deletion led to uncontrolled GSK3β activity and excessive inflammatory immune responses. Thus, our findings indicate that CUL4B functions to restrict TLR-triggered inflammatory responses through regulating the AKT-GSK3β pathway.


Deep ocean water alters the cholesterol and mineral metabolism of squid Todarodes pacificus and suppresses its weight loss.
This study is the first to demonstrate that deep ocean water (DOW) has physiological significant effects on squid. After 36 h of rearing squids, those reared with DOW had significantly higher total and free cholesterol levels and lower alanine transaminase activity in hemolymph as compared with those reared with surface sea water (SSW). SSW rearing also resulted in 6.95% weight loss, while DOW rearing caused only 2.5% weight loss, which might be due to liver metabolism suppression. Furthermore, both monovalent (sodium, chloride, and potassium ions) and divalent (calcium, inorganic phosphorus, and magnesium ions) ions in hemolymph were elevated when reared with DOW compared to those when reared with SSW. A study of genes expressed in the brain revealed that five genes were specifically remarked in DOW rearing. Most altered genes were neuropeptides, including those from vasopressin superfamily. These neuropeptides are involved in cholesterol and/or mineral metabolisms and physiological significant effects on squid. This study is the first report the effects of DOW on cholesterol and mineral metabolism of squid and will contribute to squid aquaculture using DOW.


Assessment of uterine involution in bitches using B-mode and Doppler ultrasonography.
The aim of this study was to measure the uterine diameter by B-mode and Doppler velocimetry patterns of uterine arteries in postpartum female dogs after normal delivery or cesarean section (c-section). Ten female dogs were assessed on weeks 0, 1, 2, 3 and 4 postpartum. Only at week 0, bitches submitted to c-section presented higher body diameters and uterine horns when compared to normal delivery. It was observed a reduction in uterine diameters over the weeks in both groups. In general, bitches submitted to c-section presented lower uterine perfusion. Each group presented distinct Doppler velocimetric characteristics. It was concluded that the B-mode ultrasound and Doppler are important tools for assessing puerperal uterine with distinct characteristics influenced by the type of delivery.


Identification and characterization of a novel calcyclin binding protein (CacyBP) gene from Apis cerana cerana.
Calcyclin binding protein (CacyBP), a homolog of Sgt1, was shown to interact with some S100 proteins, Skp1, tubulin, actin and ERK1/2 kinases. Studies have also shown that CacyBP is a neuronal protein in mammals. Limited information is available regarding the properties and functions of CacyBP in insects. Here, we cloned and characterized a novel CacyBP gene, named AccCacyBP, from honeybee (Apis cerana cerana). Bioinformatic analysis indicated that AccCacyBP was highly conserved and closely related to the CacyBP of other insects. Promoter analysis revealed a number of putative tissue, development and stress-related transcription factor-binding sites. RT-qPCR demonstrated that AccCacyBP was expressed at all of the stages of development, especially in the brains of honeybees. Moreover, immunohistochemistry analysis showed the presence of AccCacyBP in the brain. The transcript levels of AccCacyBP in the brains of honeybees were developmentally induced and upregulated by exposure to oxidative stresses, including UV-light, acetamiprid and HgCl(2). This study demonstrates that the CacyBP gene in honeybees may be a neuronal protein involved in the developmental regulation and the stress-response of the brain of honeybees.


Validity of different methods to prenatal screening for Down's syndrom during first and second trimester pregnancy of Chinese-women.
To identify and determine the optimal method to screening for fetal Down's syndrome (DS). Three large cohorts with 17 118, 39 903, 16 646 subjects were enrolled for the first trimester double marker (pregnancy-associated plasma protein A and free β-human chorionic gonadotropin) screening (FTDMS), second trimester double marker (α-fetoprotein and free β-human chorionic gonadotropin) screening (STDMS), and second trimester triple marker (α-fetoprotein, free β-human chorionic gonadotropin and unconjugated estriol 3) screening (STTMS), respectively. The sensitivity, specificity, false positive rate (FPR), false negative rate (FNR) and the areas under ROC curves (AUCs) were estimated in order to determine the optimal screening method in women under or above 35 years old. For women under 35 years old, STTMS was the best method with a detection rate of 68.8% and FPR of 4.3% followed by the STDMS with a detection rate (sensitivity) of 66.7% and FPR of 4.9%. The FTDMS had a lower detection rate of 61.1% and FPR of 6.3%. For women above 35 years old, the detection rate of all the methods was similar, but STTMS method had a lowest FPR of 15.9%. For women under 35 years old AUCs were 0.77 (95% CI, 0.64 to 0.91), 0.81 (95% CI, 0.71 to 0.91), and 0.82 (95% CI, 0.69 to 0.96) for FTDMS, STDMS, and STTMS methods, respectively; for those above 35 years old, AUCs were 0.70 (95% CI, 0.56 to 0.83), 0.70 (95% CI, 0.59 to 0.82), 0.78 (95% CI, 0.58 to 0.97) for FTDMS, STDMS and STTMS , respectively. Findings from our study revealed that STDMS is optimal for the detection of fetal DS in pregnant women aged under 35. For individual women, if economic condition permits, STTMS is the best choice, while for women aged above 35, STTMS is the best choice in this regard.


Aqueous Two Phase System Assisted Self-Assembled PLGA Microparticles.
Here, we produce poly(lactide-co-glycolide) (PLGA) based microparticles with varying morphologies, and temperature responsive properties utilizing a Pluronic F127/dextran aqueous two-phase system (ATPS) assisted self-assembly. The PLGA polymer, when emulsified in Pluronic F127/dextran ATPS, forms unique microparticle structures due to ATPS guided-self assembly. Depending on the PLGA concentration, the particles either formed a core-shell or a composite microparticle structure. The microparticles facilitate the simultaneous incorporation of both hydrophobic and hydrophilic molecules, due to their amphiphilic macromolecule composition. Further, due to the lower critical solution temperature (LCST) properties of Pluronic F127, the particles exhibit temperature responsiveness. The ATPS based microparticle formation demonstrated in this study, serves as a novel platform for PLGA/polymer based tunable micro/nano particle and polymersome development. The unique properties may be useful in applications such as theranostics, synthesis of complex structure particles, bioreaction/mineralization at the two-phase interface, and bioseparations.


Critical role of T cell migration in bacterial superantigen-mediated shock in mice.
Bacterial superantigens have been implicated in the pathogenesis of several human diseases. Among them, toxic shock syndrome (TSS) is a prototypic acute intoxication caused by the pyrogenic exotoxin family of superantigens. In this study, we investigated the pathophysiological mechanism of TSS using the Yersinia pseudotuberculosis-derived mitogen (YPM) and its point mutants. The results indicated that YPM could induce toxic shock in BALB/c mice but not in T cell-deficient SCID mice. We found that Vbeta8(+) T cells activated by YPM migrated from peripheral blood to liver as early as 1 h after injection of YPM and that serum level of IFN-gamma was significantly elevated 4 h after YPM injection. Co-administration of anti-IFN-gamma antibody or anti-YPM monoclonal antibody alleviated the liver injury and protected mice from YPM-induced death. Moreover, anti-YPM antibody also suppressed the early migration of Vbeta8(+) T cells from the peripheral circulation and the elevation of serum IFN-gamma level, indicating a pivotal role of T cells in inducing shock in our mouse model.


Impact of 3-year changes in fasting insulin and insulin resistance indices on incident hypertension: Tehran lipid and glucose study.
To examine the association between changes in fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and insulin-glucose ratio (IGR) levels, over approximately 3 years with incident hypertension. A total of 2814 Iranian participants (1123 men) without hypertension and known diabetes at baseline and the first examination were followed for a median of 6.32 years. The associations between quartiles of changes in fasting insulin and IR indices with incident hypertension were assessed using multivariate Cox proportional hazard regression analyses with first quartile as reference. The models were adjusted for baseline values of insulin or each IR index, and age, sex, smoking, physical activity, educational levels, marital status, history of cardiovascular diseases, baseline levels of systolic and diastolic blood pressures, estimated glomerular filtration rate, triglycerides, total cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose (only for insulin change) and both body mass index (BMI) per se, and its change. Akaike's information criteria (AIC) was applied as indicator for goodness of fit of each predictive model. The discrimination ability of models was calculated using the Harrell's C statistic. During the study, 594 incident cases of hypertension (253 men) were identified. The 4th quartile of changes in insulin, HOMA-IR, and IGR showed hazard ratios (95% confidence interval) of 1.31 (1.01-1.69), 1.18 (0.92-1.52), and 1.53 (1.18-1.98) for hypertension, respectively, in fully-adjusted models. Changes in fasting insulin levels and IR indices showed significant increasing trends for incident hypertension, moving from 1st to 4th quartiles (all P-values < 0.05). Focusing on model fitness, no superiority was found between changes in fasting insulin, HOMA-IR, and IGR to predict incident hypertension. The discriminatory powers of changes in fasting insulin and IR indices as assessed by C index were similar (i.e. about 80%). Changes in fasting insulin and IR indices were significantly associated with developing hypertension among normotensive population even after considering BMI changes.


Pneumoperitoneum occurring during double-contrast enema.
A case of pneumoperitoneum occurring during double-contrast barium enema is described. Cases reported to date indicate that colonic rupture during a double-contrast enema is likely to result in exit of air rather than barium from the colon. The diagnostic implicatons of this observation are considered. The potentially high pressure generated by bulb-type inflators is discussed, and caustion is advised against overdistending the colon during double-contrast enemas.


The FHA domain of PNKP is essential for its recruitment to DNA damage sites and maintenance of genome stability.
Polynucleotide kinase phosphatase (PNKP) has dual enzymatic activities as kinase and phosphatase for DNA ends, which are the prerequisite for the ligation, and thus is involved in base excision repair, single-strand break repair and non-homologous end joining for double-strand break (DSB) repair. In this study, we examined mechanisms for the recruitment of PNKP to DNA damage sites by laser micro-irradiation and live-cell imaging analysis using confocal microscope. We show that the forkhead-associated (FHA) domain of PNKP is essential for the recruitment of PNKP to DNA damage sites. Arg35 and Arg48 within the FHA domain are required for interactions with XRCC1 and XRCC4. PNKP R35A/R48A mutant failed to accumulate on the laser track and siRNA-mediated depletion of XRCC1 and/or XRCC4 reduced PNKP accumulation on the laser track, indicating that PNKP is recruited to DNA damage sites via the interactions between its FHA domain and XRCC1 or XRCC4. Furthermore, cells expressing PNKP R35A/R48A mutant exhibited increased sensitivity toward ionizing radiation in association with delayed SSB and DSB repair and genome instability, represented by micronuclei and chromosome bridges. Taken together, these findings revealed the importance of PNKP recruitment to DNA damage sites via its FHA domain for DNA repair and maintenance of genome stability.


Effects of Neostigmine and Sugammadex for Reversal of Neuromuscular Blockade on QT Dispersion Under Propofol Anesthesia: A Randomized Controlled Trial.
Reversal of non-depolarizing neuromuscular blocking agent neostigmine is associated with QT prolongation under general anesthesia. To clarify the effects of neostigmine and sugammadex on hemodynamic status, the QT interval and QT dispersion after reversal of neuromuscular blockade were evaluated with a 12-lead electrocardiogram. To exclude QT prolongation due to sevoflurane, the present study was performed under propofol anesthesia. After receiving approval from the ethics committee of Dokkyo Medical University Hospital, 40 patients with American Society of Anesthesiologists physical status I or II were randomly allocated to group N (n = 20) or group S (n = 20). Group N was administered neostigmine (40 μg/kg) and atropine (20 μg/kg), while Group S was administered sugammadex (4 mg/kg) for reversal of neuromuscular blockade after surgery. The changes in RR interval, QT interval (QT), corrected QT interval (QTc), QT dispersion (QTD), and corrected QT dispersion (QTcD) before and after administration of reversal agents were recorded using computerized measurements. Statistical analysis was performed using two-way analysis of variance. The RR interval significantly decreased after reversal of the neuromuscular blockade in group N, compared with group S (p < 0.05). Compared with group S, the QT decreased, whereas QTc and QTcD increased, in group N (p < 0.05). Sugammadex was not found to alter QT, QTc, QTD, or QTcD throughout the study. In the present study, a mixture of neostigmine and atropine, but not sugammadex, increased QTc and QTcD under propofol anesthesia. Thus, neostigmine may cause electrocardiogram abnormalities that could precede the development of fatal arrhythmias.


Hypofrontality and cognitive impairment in schizophrenia: dynamic single-photon tomography and neuropsychological assessment of schizophrenic brain function.
Regional cerebral blood flow (rCBF) was assessed in 40 chronic male schizophrenic patients (20 medicated, 20 unmedicated) and 31 matched normal controls with Dynamic Single-photon Emission Computed Tomography (D-SPECT). Blind analyses of normalized color-coded tomograms revealed significant bifrontal and bitemporal rCBF deficits in the patient group. Frontal flow deficits were most prominent in paranoid patients (n = 21) and right temporal deficits were most prominent in nonparanoid patients (n = 19). These relative regional declines were observed within the context of significantly elevated hemispheric blood flow in schizophrenics compared with controls. Reduced left frontal rCBF was associated with neuropsychological impairment on the Wisconsin Card Sorting Test and Luria-Nebraska Battery. Increased hemispheric CBF was correlated with the presence of positive schizophrenic symptoms. Medication status was unrelated to rCBF. These findings demonstrate that hypofrontality has important implications for cognitive function in some schizophrenic individuals.


Subtle presentations of post-traumatic stress disorder. Diagnostic issues.
The authors present a set of diagnostic procedures designed to detect subtle presentations of post-traumatic stress disorder (PTSD). Defined as a Type II diagnostic error (a false negative), the authors examine several sources of subtle presentations of PTSD. These include imperfect diagnostic instruments, high base rates, imperfect memory of critical events, imperfect reporting of signs and symptoms, imperfect interpretation of presented signs and symptoms, and diagnostic decisions based on informal clinical judgment. The authors believe that a multistage diagnostic procedure, using instruments with known psychometric properties while simultaneously looking for converging evidence is the best safeguard against missing an appropriate diagnosis of post-traumatic stress disorder.


Comparison of the priming effects of pulsatile and continuous insulin delivery on insulin action in man.
Insulin is normally secreted in man in regular pulses every 5 to 15 minutes. Disordered pulsation has been demonstrated in several insulin-resistant states and it is unclear whether this represents a primary beta-cell defect contributing to impairment of peripheral insulin action or rather is a consequence of insulin resistance. Basal or near basal insulin administration by pulsatile infusion augments hypoglycemic effect and improves insulin-mediated glucose uptake compared with insulin by continuous infusion. To date no study has examined whether normal basal insulin pulsatility is required to preserve subsequent insulin sensitivity during hyperinsulinemia. We studied the effect of overnight pulsatile versus continuous basal insulin on a subsequent hyperinsulinemic euglycemic clamp. Nineteen normal volunteers (male:female ratio, 17:2; mean age +/- SEM, 26.1 +/- 2.3 years) were studied on 2 occasions each. Endogenous insulin secretion was inhibited by octreotide (0.43 microg kg(-1). h(-1)) and replaced overnight at 5.4 mU kg(-1). h(-1) either by continuous infusion or in 2-minute pulses every 13 minutes (n = 10) or every 7 minutes (n = 9). Glucagon was replaced at physiological concentration by continuous infusion (30 ng. kg(-1). h(-1)). Venous plasma glucose overnight was not significantly different between the pulsatile and continuous protocols. After discontinuing the overnight insulin infusion, insulin action was assessed during a hyperinsulinemic euglycemic clamp (1 mU kg(-1). h(-1)). Glucose infusion rates at steady-state during the hyperinsulinemic clamp were similar between continuous and both frequencies of pulsatile infusion (continuous 44.6 +/- 4.3 micromol. kg(-1). min(-1) v 13-minute pulsatile 41.7 +/- 5.9 micromol. kg(-1). min(-1), P =.27; continuous 34.6 +/- 2.5 micromol. kg(-1) min(-1) v 7-minute pulsatile 41.4 +/- 3.2 micromol. kg(-1). min(-1), P =.08). We conclude that overnight pulsatile compared with continuous insulin administration has no different effect on subsequent peripheral insulin-mediated glucose uptake. A priming effect cannot therefore explain the previously demonstrated association between endogenous insulin pulse frequency and peripheral insulin action.