Staged surgically created type B aortic dissection model with endovascular reintervention for different morphological features.
Understanding morphology and how this relates to treatment strategy is critical for achieving remodelling in aortic dissection. A controllable and reproducible large animal model is required for investigating new therapeutic devices and interventions. Our experimental protocol involved the development of surgically created type B aortic dissection (TBAD) and endovascular reintervention-induced TBAD porcine models. The sample was randomly divided into 2 groups: 1 underwent a secondary tear creation (STC) procedure and the other underwent a false lumen extension (FLE) procedure. Anatomical features were observed at 1 and 3 months, and 2 animals in each group were euthanized at 3 months after the procedures. The aorta and main branches were harvested en bloc, cross-sectioned and prepared for histological examination. All surgically created TBAD models were successfully generated, and no unintended complications occurred. The endovascular reintervention-induced TBAD model was successfully created in 11 of 12 animals, with 6 in the STC group and 5 in the FLE group. In the STC group, the intraoperative mean diameter of the new secondary tear was 7.23 mm, and a slight increase was observed at first 30 days (P = 0.0026). In the FLE group, the intraoperative new propagation length was (235.80 ± 84.94) mm. The FL propagation length at the 1-month follow-up was significantly longer than that measured intraoperatively (P = 0.0362). Histological evaluation demonstrated that the elastic fibres in the media layer of the aortic wall were disrupted and appeared to be significantly stretched on the adventitial side of the false lumen. Our endovascular reintervention is a reliable, minimally invasive approach for producing specific TBAD models with different morphologies.


[Corrigendum] Knockdown of eukaryotic translation initiation factor 4E suppresses cell growth and invasion, and induces apoptosis and cell cycle arrest in a human lung adenocarcinoma cell line.
Mol Med Rep 12:[Related article:] 7971–7978, 2015; DOI: 10.3892/mmr.2015.4468 Following the publication of this article, an interested reader drew to our attention an anomaly associated with the presentation of Fig. 3A. The images selected for the '72 h Blank' and the '72 h Mock' panels were inadvertently selected from the same original photograph. This error arose during the editing process of our paper with a professional English Editing Service, and our failure to notice the mismatching of the images during the final proofreading of the manuscript prior to submission. A corrected version of Fig. 3 is presented here (right), which includes the corrected images for the 72 h Blank' and the '72 h Mock' panels. This error did not affect the overall conclusions reported in the present study. We sincerely apologize for this mistake, and thank the reader of our article who drew this matter to our attention. Furthermore, we regret any inconvenience this mistake has caused.


Effects of a human plasma fraction on leucocyte migration into inflammatory exudates.
A fraction prepared from normal human plasma inhibits the migration of polymorphonuclear and mononuclear leucocytes into inflammatory exudates produced by the intrapleural injection of carrageeman or turpentine by the subcutaneous implantation of polyvinyl sponges in the rat. The mechanism of the effect does not involve complement depletion.


Novel functions of grass carp three p40 isoforms as modulators of Th17 signature cytokine expression in head kidney leukocytes.
Interleukin (IL)-12p40, a component of IL-12 and IL-23, can be secreted as monomer and homodimer in mammals. Our previous study has proved the existence of natural three p40 isoforms and their proinflammatory properties in grass carp. In the present study, we unexpectedly found that recombinant grass carp p40a/b/c (rgcp40a, rgcp40b and rgcp40c) were able to enhance the mRNA levels of grass carp il-17a/f1 (gcil-17a/f1) in a dose- and time-dependent manner in head kidney leukocytes (HKLs). In agreement with these findings, the enzyme-linked immunosorbent assay (ELISA) showed that rgcp40a, rgcp40b and rgcp40c markedly stimulated gcIl-17a/f1 secretion from the HKLs. Together with their stimulatory effects on grass carp gcil-22 and gcil-26 expression, our data suggested their potential to mediate Th17-like response in grass carp. To support this notion, we investigated the underlying mechanisms for the regulation of rgcp40 isoforms on gcil-17a/f1 expression, and found that three rgcp40 isoforms significantly induced the activation of Erk, Jnk and Stat3 pathways in a time-dependent oscillation in the same cell model. Moreover, three rgcp40 isoforms-induced gcil-17a/f1 mRNA expression was suppressed by the inhibition on Erk, Jnk and Stat3 pathways, suggesting the signaling pathways in the p40 isoforms-mediating il-17a/f1 transcription. These studies for the first time proved the involvement of three gcp40 isoforms in mediating Th17 signature cytokine expression in fish immune cells, therefore providing new insights into the roles of p40 in teleost immunity.


New antifungals selected by molecular topology.
Molecular topology has been applied to find the new lead antimycotic compounds. Among the selected compounds stands out 3,3'-(4,4'-Biphenylene)bis(2,5-diphenyl-2H-tetrazolium chloride), Benztropine mesylate and Dicyclopentamethylenethiuram disulphide, with minimum inhibitory concentrations between 1.6 and 2 micrograms/mL.


Severe Cholestasis and Bile Acid Nephropathy From Anabolic Steroids Successfully Treated With Plasmapheresis.
Severe cholestasis with anabolic androgenic steroids is well-known to cause acute liver injury. Treatment is usually supportive after withdrawal of the offending agent. Acute kidney injury (AKI) frequently occurs in acute liver injury and may complicate management and prognosis. We highlight the use of plasmapheresis resulting in rapid improvement in cholestatic jaundice with resolution of AKI. Plasmapheresis should be considered in special cases in which there is progressive clinical decline despite supportive care.


Meeting information needs in health policy and public health: priorities for the National Library of Medicine and The National Network of Libraries of Medicine.
Those seeking information in health policy and public health are not as well served as those seeking clinical information. Problems inhibiting access to health policy and public health information include the heterogeneity of professionals seeking the information, the distribution of relevant information across disciplines and information sources, scarcity of synthesized information useful to practitioners, lack of awareness of available services or training in their use, and lack of access to information technology or to knowledgeable librarians and information specialists. Since 1990, the National Library of Medicine and the National Network of Libraries of Medicine have been working to enhance information services in health policy and public health through expanding the coverage of the NLM collection, building new databases, and engaging in targeted outreach and training initiatives directed toward segments of the health policy and public health communities. Progress has been made, but more remains to be done. Recommendations arising from the meeting, Accessing Useful Information: Challenges in Health Policy and Public Health, will help NLM and the National Network of Libraries of Medicine to establish priorities and action plans for the next several years.


Chemoimmunotherapy of canine lymphoma with adjuvant canine monoclonal antibody 231.
Chemoimmunotherapy with adjuvant CL/MAb 231 offers an alternative treatment approach for canine lymphoma. Results of treatment and prognostic factors are discussed and compared with previously published chemotherapy results.


Death certification in fractured neck of femur.
Fracture of the neck of the femur is a major public health problem within the elderly population of most industrialised countries whose health services are increasingly being taken up with its management. Moreover, within Britain, there is evidence of a real increase in its incidence even allowing for the ageing of the population. A condition whose aetiology is still far from clear (and where no strategy for prevention can therefore be formulated), and which is of such importance to the planning and provision of services demands detailed investigation and careful monitoring. Mortality data are an important part of epidemiological studies of disease problems and, in Britain, in resource allocation through the Resource Allocation Working Party (RAWP) formula. In this study, a cohort of 2,631 elderly patients, resident in the largest health district in the country, and admitted to hospitals over a seven year period with the diagnosis of fractured neck of femur, was assembled. Hospital records were linked to national mortality data to determine whether patients had died and, where this was so, to record underlying cause of death. A total of 930 deaths occurred within the study cohort but only 52 were certified as dying from fractured neck of femur; even amongst those who died in the hospital to which they were admitted with the fracture, less than a fifth of deaths were attributed to the fracture as underlying cause. Diseases of the circulatory system accounted for almost half of all underlying causes of death and bronchopneumonia a further 20%. These findings suggest a gross undercertification of fractured neck of femur as a cause of death in the elderly and are consistent with other studies. They may be explained by a failure of junior hospital doctors to understand the importance of accurate certification of cause of death and a misguided attempt to reduce the burden to coroners of having to consider each death from this cause.(ABSTRACT TRUNCATED AT 250 WORDS)


An additional bolus of rapid-acting insulin to normalise postprandial cardiovascular risk factors following a high-carbohydrate high-fat meal in patients with type 1 diabetes: A randomised controlled trial.
To evaluate an additional rapid-acting insulin bolus on postprandial lipaemia, inflammation and pro-coagulation following high-carbohydrate high-fat feeding in people with type 1 diabetes. A total of 10 males with type 1 diabetes [HbA1c 52.5 ± 5.9 mmol/mol (7.0% ± 0.5%)] underwent three conditions: (1) a low-fat (LF) meal with normal bolus insulin, (2), a high-fat (HF) meal with normal bolus insulin and (3) a high-fat meal with normal bolus insulin with an additional 30% insulin bolus administered 3-h post-meal (HFA). Meals had identical carbohydrate and protein content and bolus insulin dose determined by carbohydrate-counting. Blood was sampled periodically for 6-h post-meal and analysed for triglyceride, non-esterified-fatty acids, apolipoprotein B48, glucagon, tumour necrosis factor alpha, fibrinogen, human tissue factor activity and plasminogen activator inhibitor-1. Continuous glucose monitoring captured interstitial glucose responses. Triglyceride concentrations following LF remained similar to baseline, whereas triglyceride levels following HF were significantly greater throughout the 6-h observation period. The additional insulin bolus (HFA) normalised triglyceride similarly to low fat 3-6 h following the meal. HF was associated with late postprandial elevations in tumour necrosis factor alpha, whereas LF and HFA was not. Fibrinogen, plasminogen activator inhibitor-1 and tissue factor pathway levels were similar between conditions. Additional bolus insulin 3 h following a high-carbohydrate high-fat meal prevents late rises in postprandial triglycerides and tumour necrosis factor alpha, thus improving cardiovascular risk profile.


Acute respiratory distress syndrome following administration of gadolinium contrast agent: a case report.
Gadolinium-based contrast agents are used extensively in magnetic resonance imaging to assist diagnosis of medical conditions. Despite their documented safety profile, severe adverse events do occur, and their documentation may serve to raise the awareness of the medical community. We report the case of a 15-year-old white Latin American female patient admitted to the intensive care unit for acute respiratory distress syndrome following administration of gadolinium. She did not have rash or tongue swelling but developed hypotension responsive to fluid administration and severe hypoxemia. Chest computed tomography revealed bilateral pulmonary compromise with multiple confluent consolidations. She received methylprednisolone and noninvasive ventilatory support including bilevel positive airway pressure ventilation and high-flow nasal cannula, and underwent a rapid recovery. Gadolinium-based contrast agent-induced acute respiratory distress syndrome, albeit rare, should be included in the differential diagnosis of respiratory failure shortly after magnetic resonance imaging, which is nowadays a frequent diagnostic procedure, potentially increasing the awareness of this serious complication.


New insights into the cellular, biochemical, and molecular basis of postmenopausal and senile osteoporosis: roles of IL-6 and gp130.
It is well established that osteoclasts, the cells responsible for bone resorption, are derived from hematopoietic progenitors (CFU-GM), whereas the bone-forming osteoblasts are of the same lineage as the mesenchymal stromal cells of the bone marrow. Moreover, it is widely accepted that osteoclast formation depends on cells of the stromal/osteoblastic lineage. The appreciation of the ontogeny of osteoclasts and osteoblasts, the interaction between them, and the role of local factors that regulate their development has led to the emergence of new insights into the pathophysiology of the osteopenias associated with estrogen deficiency and senescence. Consistent with histomorphometric data from humans, there is now evidence from studies in animal models suggesting that a critical cellular change caused by the loss of ovarian, as well as testicular, function is an increase in osteoclastogenesis. This change is apparently mediated by an increase in the production of the osteoclastogenic cytokine interleukin-6 by cells of the bone marrow, which follows the removal of an inhibiting control of estrogens or androgens on IL-6. The inhibiting effect of sex steroids on IL-6 production is mediated by their respective receptors and is exerted indirectly on the transcriptional activity of the proximal 225 bp sequence of the IL-6 gene promoter. Besides its effects on IL-6 production, loss of gonadal function may also cause an increase in the sensitivity of the osteoclastic precursors to the action of cytokines such as IL-6, due to an upregulation of the gp130 signal transduction pathway.(ABSTRACT TRUNCATED AT 250 WORDS)


Astrocyte differentiation selectively upregulates CCL2/monocyte chemoattractant protein-1 in cultured human brain-derived progenitor cells.
Chemokines (chemoattractant cytokines) and their receptors are present in the brain and may play roles in both neurodevelopment and neuropathology. Increased brain levels of monocyte chemoattractant protein-1 (MCP-1), also known as CCL2, are found in patients with human immunodeficiency virus type 1 (HIV-1)-associated dementia and other acute and chronic neurologic diseases. Although the function of CCL2 in the brain is unclear, it is believed that upregulation of this chemokine during neuropathologic or neuroinflammatory conditions leads to recruitment of activated monocytes into the brain, where they differentiate into macrophages producing neurotoxic and inflammatory molecules. We recently showed that human fetal brain-derived progenitor cells are susceptible to HIV-1 and JC virus infection, and that differentiation toward an astrocyte phenotype increased virus production from these cells. In the current study, we found that in the absence of infection, progenitors produced moderate levels of CCL2 (5.6 ng per million cells). Astrocyte differentiation over 3 weeks increased CCL2 protein levels 30-fold in a biphasic manner, whereas neuronal differentiation decreased production 20-fold. Electromobility shift assays (EMSAs) demonstrated increased nuclear NF-kappaB levels within 2 h of initiating astrocyte differentiation, and inhibitors of NF-kappaB activation partially blocked the CCL2 increase in differentiating astrocytes. Transfection of progenitors with mutated CCL2 promoter/CAT reporter constructs showed that the distal promoter region, containing NF-kappaB and NF-I binding sites, is important for differentiation-induced CCL2 upregulation. Together these results suggest that the transcription factor NF-kappaB, and possibly NF-I, contribute to the upregulation of CCL2 chemokine production during the differentiation of human progenitor cells toward an astrocyte phenotype.


Lessons learned and questions raised during and post-COVID-19 anthropopause period in relation to the environment and climate.
In the first part, this work reports that during the global "anthropopause" period, that was imposed in March and April 2020 for limiting the spread of COVID-19, the concentrations of basic air pollutants over Europe were reduced by up to 70%. During May and June, the gradual lift of the stringent measures resulted in the recovery of these reductions with pollution concentrations approaching the levels before the lockdown by the end of June 2020. In the second part, this work examines the alleged correlations between the reported cases of COVID-19 and temperature, humidity and particulate matter for March and April 2020 in Europe. It was found that decreasing temperatures and relative humidity with increasing concentrations of particulate matter are correlated with an increase in the number of reported cases during these 2 months. However, when these calculations were repeated for May and June, we found a remarkable drop in the significance of the correlations which leads us to question the generally accepted inverse relation between pandemics and air temperature at least during the warmer months. Such a relationship could not be supported in our study for SARS-CoV-2 virus and the question remains open. In the third and last part of this work, we examine the question referring to the origin of pandemics. In this context we have examined the hypothesis that the observed climate warming in Siberia and the Arctic and the thawing of permafrost could result to the release of trapped in the permafrost pathogens in the atmosphere. We find that although such relations cannot be directly justified, they present a possible horrifying mechanism for the origin of viruses in the future during the developing global warming of our planet in the decades to come. Overall the findings of our study indicate that: (1) the reduction of anthropogenic emissions in Europe during the "anthropopause" period of March and April 2020 was significant, but when the lockdown measures were raised the concentrations of atmospheric pollutants quickly recovered to pre-pandemic levels and therefore any possible climatic feedbacks were negligible; (2) no robust relationship between atmospheric parameters and the spread of COVID-19 cases can be justified in the warmer part of the year and (3) more research needs to be done regarding the possible links between climate change and the release of new pathogens from thawing of permafrost areas.


A new species of Myxozoa, Henneguya rondoni n. sp. (Myxozoa), from the peripheral nervous system of the Amazonian fish, Gymnorhamphichthys rondoni (Teleostei).
Henneguya rondoni n. sp. found in the peripheral lateral nerves located below the two lateral lines of the fish Gymnorhamphichthys rondoni (Teleostei, Rhamphichthyidae) from the Amazon river is described using light and electron microscopy. Spherical to ellipsoid cysts measuring up to 110 microm in length contained only immature and mature spores located in close contact with the myelin sheaths of the nervous fibres. Ellipsoidal spores measured 17.7 (16.9-18.1)-microm long, 3.6 (3.0-3.9)-microm wide, and 2.5 (2.2-2.8)-microm (n=25) thick. The spore body measuring 7.0 (6.8-7.3)-microm long was formed by two equal symmetric valves, each with an equal tapering tail 10.7 (10.3-11.0) microm in length. The tails were composed of an internal dense material surrounded by an external homogeneous sheath of hyaline substance. The valves surrounded two equal pyriform polar capsules measuring 2.5 (2.2-2.8)-microm long and 0.85 (0.79-0.88)-microm (n=25) wide and a binucleated sporoplasm cell containing globular sporoplasmosomes 0.38 (0.33-0.42) microm (n=25) in diam. with an internal eccentric dense structure with half-crescent section. Each polar capsule contains an anisofilar polar filament with 6-7 turns obliquely to the long axis. The matrix of the polar capsule was dense and the wall filled with a hyaline substance. The spores differed from those of previously described species. Based on the ultrastructural morphology of the spore and specificity to the host species, we propose a new species name H. rondoni n. sp.


Correction: Faria, A.V.S. et al., Targeting Tyrosine Phosphatases by 3-Bromopyruvate Overcomes Hyperactivation of Platelets from Gastrointestinal Cancer Patients. J. Clin. Med. 2019, 8, 936.
The authors wish to make the following correction to their paper [...].


Calcium modulates osmosensitive taurine efflux in HeLa cells.
The role of Ca2+ in the signaling transduction pathway involved in osmosensitive taurine efflux in HeLa cells was studied using radiotracer efflux techniques. Taurine efflux induced by extracellular hypotonicity was decreased by 85% by removal of extracellular Ca2+ and simultaneous depletion of intracellular Ca2+ stores with thapsigargin. Extracellular Ca2+ removal, thapsigargin treatment, or addition of Gd3+ all decreased taurine efflux by approximately 50%. To explore the putative signal transduction pathways involved in swelling-induced taurine efflux, HeLa cells were exposed to PP1, an inhibitor of the Src family of tyrosine kinases, the phospholipase C inhibitor U73122, the IP3 receptor antagonist 2-APB, and the generic protein kinase C inhibitor chelerythrine. All of these treatments caused approximately 50% inhibition of taurine release in Ca2+-rich extracellular medium and approximately 85%-90% in Ca2+-free conditions. The inhibitors of the conventional protein kinase C isoforms BIM-1 and Gö6976 reduced taurine efflux to a lesser extent. Acute (10-min) exposure to the phorbol ester tetradecanoyl phorbol acetate (TPA) increased taurine efflux in 25%, whilst overnight exposure had an inhibitory effect decreasing efflux by 22%. A working model for activation of osmosensitive taurine efflux in HeLa cells involving different Ca2+ signaling pathways is presented.


Antibiotic bonded nephrostomy catheters for percutaneous nephrostomies.
A prospective controlled trial of the effectiveness of a cefoxitin-bonded nephrostomy catheter was undertaken to determine the effectiveness of an antibiotic bonded catheter in decreasing the infectious complications of percutaneous nephrostomy. The study concludes that bonding of the antibiotic cefoxitin to percutaneous nephrostomy catheters did not influence the incidence of bacteriuria or urinary tract infection. In addition, observations on the overall incidence of complications from percutaneous nephrostomy are made.


Prediction of sudden cardiac death with automated high-throughput analysis of heterogeneity in standard resting 12-lead electrocardiograms.
Heterogeneity of depolarization and repolarization underlies the development of lethal arrhythmias. We investigated whether quantification of spatial depolarization and repolarization heterogeneity identifies individuals at risk for sudden cardiac death (SCD). Spatial R-, J-, and T-wave heterogeneity (RWH, JWH, and TWH, respectively) was analyzed using automated second central moment analysis of standard digital 12-lead electrocardiograms in 5618 adults (2588, 46% men; mean ± SEM age 50.9 ± 0.2 years), who took part in the epidemiological Health 2000 Survey as representative of the entire Finnish adult population. During the follow-up period of 7.7 ± 0.2 years, a total of 72 SCDs occurred (1.3%), with an average yearly incidence rate of 0.17% per year. Increased RWH, JWH, and TWH in left precordial leads (V4-V6) were univariately associated with SCD (P < .001 for each). When adjusted with standard clinical risk markers, JWH and TWH remained independent predictors of SCD. Increased TWH (≥102 µV) was associated with a 1.7-fold adjusted relative risk for SCD (95% confidence interval [CI] 1.0-2.9; P = .048) and increased JWH (≥123 µV) with a 2.0-fold adjusted relative risk for SCD (95% CI 1.2-3.3; P = .006). When both TWH and JWH were above the threshold, the adjusted relative risk for SCD was 2.9-fold (95% CI 1.5-5.7; P = .002). When RWH (≥470 µV), JWH, and TWH were all above the threshold, the adjusted relative risk for SCD was 3.2-fold (95% CI 1.4-7.1; P = .009). Second central moment analysis of standard resting 12-lead electrocardiographic morphology provides an ultrarapid means for the automated measurement of spatial RWH, JWH, and TWH, enabling analysis of high subject volumes and screening for SCD risk in the general population.


Association between emergency physician self-reported empathy and patient satisfaction.
Higher physician self-reported empathy has been associated with higher overall patient satisfaction. However, more evidence-based research is needed to determine such association in an emergent care setting. To evaluate the association between physician self-reported empathy and after-care instant patient-to-provider satisfaction among Emergency Department (ED) healthcare providers with varying years of medical practice experience. A prospective observational study conducted in a tertiary care hospital ED. Forty-one providers interacted with 1,308 patients across 1,572 encounters from July 1 through October 31, 2016. The Jefferson Scale of Empathy (JSE) was used to assess provider empathy. An after-care instant patient satisfaction survey, with questionnaires regarding patient-to-provider satisfaction specifically, was conducted prior to the patient moving out of the ED. The relation between physician empathy and patient satisfaction was estimated using risk ratios (RR) and their corresponding 95% confidence limits (CL) from log-binomial regression models. Emergency Medicine (EM) residents had the lowest JSE scores (median 111; interquartile range [IQR]: 107-122) and senior physicians had the highest scores (median 119.5; IQR: 111-129). Similarly, EM residents had the lowest percentage of "very satisfied" responses (65%) and senior physicians had the highest reported percentage of "very satisfied" responses (69%). There was a modest positive association between JSE and satisfaction (RR = 1.04; 95% CL: 1.00, 1.07). This study provides evidence of a positive association between ED provider self-reported empathy and after-care instant patient-to-provider satisfaction. Overall higher empathy scores were associated with higher patient satisfaction, though minor heterogeneity occurred between different provider characteristics.


Effects of short chain fatty acids on mucosal proliferation and inflammation of ileal pouches in patients with ulcerative colitis and familial polyposis.
To verify whether short chain fatty acids (SCFA) alter the proliferative and endoscopic pattern of the mucosa in ileal pouches of ulcerative colitis (UC) or familial adenomatous polyposis (FAP) patients. We studied patients after proctocolectomy carrying a pelvic ileal pouch for FAP or UC (noncanalized pouches in 10 UC and 4 FAP patients and canalized pouches in 6 UC and 5 FAP patients). Patients with noncanalized pouches were treated twice daily for one week with 30 ml of a SCFA solution (60 mM sodium acetate, 30 mM sodium propionate, 40 mM sodium butyrate, and 22 mM sodium chloride, pH 7); patients with canalized pouches were treated with the same solution twice daily for two weeks. Pouch mucosal biopsies were collected before and after SCFA. Mucosal proliferation was assessed by incorporation of [3H]thymidine in vitro and autoradiography. In UC patients proliferation did not vary in noncanalized pouches but was significantly reduced in canalized pouches after SCFA. In FAP patients SCFA did not alter proliferation. No significant effects of SCFA were observed on daily defecation frequency, endoscopic appearance, or histopathology of the pouches. SCFA do not control inflammation and clinical functions but reduce cell proliferation in UC patients. On the contrary, FAP patients are refractory to SCFA.


Disorders of consciousness: preliminary data supports added value of extended behavioural assessment.
The use of validated behavioural assessment scales in assessment of patients with Disorders of Consciousness (DOC) is well established. However, there is little evidence to guide decisions on total time spent in behavioural assessment. To assess whether brief behavioural assessment was as effective as extended behavioural assessment in detecting non-vegetative behaviours. Consecutive patients with suspected DOC were assessed with two standardized instruments: Coma Recovery Scale Revised (CRS-R) and Sensory Modality Assessment and Rehabilitation Technique (SMART). Assessors were blinded to results from the other scale at the point of assessment. Two administrations of CRS-R together took 50-60 minutes ('brief' assessment). One complete SMART assessment took 600 minutes ('extended' assessment). Patients were classified as being in a vegetative state (VS) or minimally conscious state (MCS)/emerged from minimally conscious state (EMCS), following brief and extended assessment. Ten patients were assessed. Brief and extended assessment yielded the same diagnostic category (VS or MCS) for six patients and different categories for four, with extended assessment detecting higher level behaviours. Brief behavioural assessment was not as effective as extended assessment in detecting non-vegetative behaviours. Total time spent in behavioural assessment is likely important. Further studies and clearer clinical guidance are needed.


H-reflex in abductor hallucis and postural performance between flexible flatfoot and normal foot.
Morphological changes of the abductor hallucis muscle (AbH) in flexible flatfoot (FF) individuals influence regulations of the medial longitudinal arch (MLA). Prolonged and repeated stretching of AbH in flexible flatfoot may cause changes in muscle reflex properties and further influence postural performance. However, AbH muscle reflex under different postural conditions have never been examined. The purpose of this study was to investigate differences in AbH H-reflex and postural performance between individuals with normal foot (NF) alignment and FF under prone, double-leg stance (DLS), and single-leg stance (SLS) conditions. Cross-sectional study. University laboratory. Individuals with FF (n = 12) and NF (n = 12). AbH H-reflex, AbH EMG and center of pressure (CoP) displacement. Under all postural conditions, AbH H-reflex was significantly lower in the FF group (P < .05). Under the SLS condition, AbH EMG was significantly higher in the FF group (P < .05), and CoP displacement for the medial-lateral and anterior-posterior directions were significantly higher in the FF group (P < .05). With increased postural demand, FF individuals maintained their postural stability by recruiting greater AbH activities than through automatic stretch reflex, but FF individuals still showed inferior posture stability.


Fentanyl increases catecholamine oxidation current measured by in vivo voltammetry in the rat striatum.
A proposed mechanism for fentanyl-induced muscular rigidity is the effect of opioids on dopaminergic transmission in the striatum. The objective of this study was to observe the effect of fentanyl on the rat striatal catechol oxidation current (CA.OC) which reflects extracellular DOPAC (3-4,dihydroxyphenylacetic acid) concentration (a major metabolite of dopamine), as measured by in vivo voltammetry. Male Sprague-Dawley rats, anaesthetized with halothane, were stereotaxically implanted with carbon fibre electrodes in the striatum and after an initial stabilization period of an hour were given a control saline IV injection followed 30 min later by fentanyl 10 micrograms.kg-1 IV over 10 min and at 70 min by the monoamine oxidase inhibitor pargyline 70 mg.kg-1 IP. Fentanyl produced a significant (P less than 0.05 Anova) increase in CA.OC in all animals. This reached a plateau 15 min following the administration of fentanyl and was at a maximum of 148 +/- 10.2 per cent of control 35 min after the administration of fentanyl. Pargyline produced a rapid decline in CA.OC peak height which went from 143 +/- 11.6 to 39 +/- 6.8 per cent of control over 30 min. There were no significant differences between the pH, PaO2 and PaCO2 during the saline and fentanyl injection periods and there was no significant variation of blood pressure throughout the experiment. This study shows that under stable physiological conditions, fentanyl produces a significant increase in CA.OC in the rat striatum.


Technology in Muslim Moral Philosophy.
The article explores the place, role and status of technology in Muslim moral philosophy. Invoking early Muslim encounters with technology the author makes the case why technology is already deeply embedded in contemporary Muslim bioethical thinking. Due to an absence of the philosophical grounding there remains some ambivalence as to why technology is essential to Muslim ethical thinking. Countering the techno-pessimists, the author makes a case in favor of compositional thinking, namely that our thinking itself is altered by our tools and our environment. Compositional thinking opposes the representational mode of thinking that creates a dichotomy between nature versus culture, and technology versus nature. One should, however, anticipate an environment in which technology would be beneficial and not be viewed as potentially harmful.


Analyses of HH and GHK equations with another perspective: Can ion adsorption also govern trans-membrane potential?
Two mathematically distinct physiological concepts, the Goldman-Hodgkin-Katz eq. (GHK eq.) and the Hodgkin-Huxley model (HH model) were successfully associated with each other in a prior work. The previous work was performed on the following premises (i) The membrane potential is generated by ion adsorption, as opposed to the classical ion transport mechanisms, (ii) The living cell is a thermodynamically real system rather than an ideal system, and (iii) The conductance employed in the HH model is replaced by the ion activity coefficient, which is weighted with the role of conductance. Consequently, the GHK eq. was mathematically associated with the HH model through the intermediary of Boltzmann ion distribution and mass action law. To verify if our theoretical formularization could afford a physiologically, physically and chemically viable model, we performed computational analysis using the formulae (quantitative correlations between various variables) we derived in the previous work. The computational results obtained through associating the GHK eq. with the HH model validated our model and its predictions. This outcome suggests that the current prevailing physiological concepts could be expanded further, to incorporate the newly proposed mechanisms. That is, GHK eq. and HH model could be interpreted via another set of founding principles that incorporate the ubiquitous phenomena of ion-adsorption.


The gut microbiome in epilepsy.
The close relationship between epilepsy and autoimmune diseases and the fact that the cause of epilepsy is idiopathic in 60% of cases suggest that intestinal microbiota may play a role in the etiology of epilepsy. In this study, we analyzed and compared the intestinal microbiota composition of patients with idiopathic focal epilepsy (n = 30) and healthy volunteer group (n = 10) by 16s ribosomal DNA sequencing. Proteobacteria phylum was found to be higher in patients with epilepsy (25.4%) than in healthy volunteers group (1.5%). The genera of Campylobacter, Delftia, Haemophilus, Lautropia, Neisseria among Proteobacteria phylum were found to be statistically significantly higher in patients with epilepsy than in healthy volunteers (p < 0.05). Fusobacteria phylum was detected in 10.6% of the patients with epilepsy but not in the healthy volunteer group. The genus of the Fusobacteria phylum was found as Leptotrichia and Fusobacterium. In our study, taxonomic drift and significant differences in the intestinal microbiota of patients with epilepsy according to healthy volunteer group showed that autoimmune mechanisms and inflammation may have a role in the etiology of epilepsy. Our data should be supported by other studies as to the role of the intestinal microbiome in the prevention and treatment of epilepsy.


Evaluation of smears obtained by cervical scraping and an endocervical swab in the diagnosis of neoplastic disease of the uterine cervix.
A study of the supplementary value of an endocervical swab smear in addition to cervical scraping in the cytological diagnosis of cervical neoplasias is presented. The two sampling techniques were applied to a population with a high prevalence of neoplastic cervical disease. The endocervical swab smear was a useful adjunct in the detection of mild and moderate dysplasia, and a combination of the two sampling methods decreased the false negative rate in the diagnosis of intraepithelial, as well as invasive neoplasia. In the sphere of specific cytological diagnosis cervical scraping was found to be the more accurate method for diagnosing severe dysplasia and carcinoma in situ, while endocervical swab smears were more useful in diagnosing mild and moderate dysplasia. Differences between the results obtained in our study and comparable studies are discussed. It is concluded that the endocervical swab smear is a valuable adjunct to cervical scraping in the diagnosis of malignant cervical disease. It should not, however, be used as the only sampling method as it produces a higher proportion of unsatisfactory smears, and also because the severity of the epithelial lesion is more likely to be underestimated.


Smartphone aiding in analysis of Hamman's sign.
Hamman's sign refers to an unusual click that occurs in synchrony with heart sounds, and is pathognomonic for left-sided pneumothorax and spontaneous mediastinum. In this case, a 17-year-old man living in a rural area used his smartphone to record an audible clicking sound emanating from his thorax. This occurred following coughing episodes secondary to an upper respiratory tract infection. Initially, this prompted a request for an echocardiogram to exclude structural cardiac anomalies; however, Hamman's sign was also considered. This facilitated the timely diagnosis of pneumothorax to be made via a simple chest radiograph, one of the only imaging modalities available at the patient's rural health service. To promote awareness of this rare clinical phenomenon, this report also presents the patient's own sound recording of Hamman's sign and corresponding chest radiographs.


Rescue of volume-regulated anion current by bestrophin mutants with altered charge selectivity.
Mutations in human bestrophin-1 are linked to various kinds of retinal degeneration. Although it has been proposed that bestrophins are Ca(2+)-activated Cl(-) channels, definitive proof is lacking partly because mice with the bestrophin-1 gene deleted have normal Ca(2+)-activated Cl(-) currents. Here, we provide compelling evidence to support the idea that bestrophin-1 is the pore-forming subunit of a cell volume-regulated anion channel (VRAC) in Drosophila S2 cells. VRAC was abolished by treatment with RNAi to Drosophila bestrophin-1. VRAC was rescued by overexpressing bestrophin-1 mutants with altered biophysical properties and responsiveness to sulfhydryl reagents. In particular, the ionic selectivity of the F81C mutant changed from anionic to cationic when the channel was treated with the sulfhydryl reagent, sodium (2-sulfonatoethyl) methanethiosulfonate (MTSES(-)) (P(Cs)/P(Cl) = 0.25 for native and 2.38 for F81C). The F81E mutant was 1.3 times more permeable to Cs(+) than Cl(-). The finding that VRAC was rescued by F81C and F81E mutants with different biophysical properties shows that bestrophin-1 is a VRAC in S2 cells and not simply a regulator or an auxiliary subunit. F81C overexpressed in HEK293 cells also exhibits a shift of ionic selectivity after MTSES(-) treatment, although the effect is quantitatively smaller than in S2 cells. To test whether bestrophins are VRACs in mammalian cells, we compared VRACs in peritoneal macrophages from wild-type mice and mice with both bestrophin-1 and bestrophin-2 disrupted (best1(-/-)/best2(-/-)). VRACs were identical in wild-type and best1(-/-)/best2(-/-) mice, showing that bestrophins are unlikely to be the classical VRAC in mammalian cells.


Predictors of pain medication selection among patients diagnosed with fibromyalgia.
Several pharmacologic therapies have been recommended for managing fibromyalgia. However, the factors associated with each treatment initiation have not been well established. This study assessed factors that were associated with the use of duloxetine vs. other pain medications among patients with fibromyalgia. Administrative claims from a large, U.S. commercially insured population were analyzed using a retrospective cohort design. Patients with fibromyalgia who were 18 to 64 years old and initiated duloxetine vs. selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), venlafaxine, gabapentin, pregabalin, tramadol, or nontramadol opioids between January 1, 2007 and December 12, 2008 were selected. Treatment initiation was defined as no access to the same medication over the previous 90 days, with the most recent initiation date as the index date. All patients selected had at least one fibromyalgia diagnosis (ICD-9-CM: 729.1) in the 12 months prior to initiation of each study medication. Multiple logistic regression models were estimated to assess the predictors of initiating duloxetine vs. each of the other medications. The study included 117,305 patients with fibromyalgia (48 years of age on average; 76% women) who initiated duloxetine (n = 5,827), SSRIs (n = 8,620), TCAs (n = 5,424), venlafaxine (n = 2,038), gabapentin (n = 5,733), pregabalin (n = 11,152), tramadol (n = 7,312), or nontramadol opioids (n = 71,199). Common fibromyalgia-related comorbidities were low back pain (31% to 49%), osteoarthritis (14% to 21%), and sleep disturbance (10% to 15%). Controlling for demographic and clinical characteristics, patients who received pregabalin in the prior 12-month period were more likely to initiate duloxetine. Patients from other treatment cohorts, except for those in the pregabalin and nontramadol opioid cohorts, were more likely to re-initiate the same prior medication than to begin treatment with duloxetine. Other predictors of duloxetine initiation included history of rheumatoid and sleep disturbance. The presence of select comorbidities and prior use of certain medications were associated with the duloxetine initiation among working-age, commercially insured patients with fibromyalgia.


Interleukin-6 and leptin mediate lipopolysaccharide-induced fever and sickness behavior.
Pro-inflammatory cytokines, interleukin (IL)-1beta, IL-6 and tumor necrosis factor-alpha (TNF-alpha) synthesized by activated macrophages and monocytes in response to administration of lipopolysaccharide (LPS), are considered important mediators of fever and sickness behavior. We administered rat-specific antisera for TNF-alpha, IL-1beta, IL-6 and leptin, to determine the involvement of peripherally released cytokines in LPS-induced fever and sickness behavior, measured as suppression of voluntary wheel-running and food intake. Male Sprague-Dawley rats (approximately 200 g) selected for their predisposition to spontaneously run on running wheels were anaesthetized with a combination of ketamine hydrochloride (80 mg/kg i.m.) and xylazine (4 mg/kg i.m.) and implanted intra-abdominally with temperature-sensitive radiotelemeters. Rats were injected intraperitoneally with anti-rat sera to one of the following, TNF-alpha, IL-1beta, IL-6 or leptin or with pre-immune sheep serum, followed by a subcutaneous injection of either LPS (250 microg/kg) or sterile saline. Lipopolysaccharide administration induced a approximately 1.3 (0.2) degrees C fever lasting approximately 10 h and reduced voluntary running by 93 (8.6)% and food intake by 51 (21.3)% compared to the saline response (ANOVA, P<0.05). Injection of anti-IL-6 serum or anti-leptin serum abolished the LPS-induced fever, anti-TNF-alpha serum affected only the early phase of fever and anti-IL-1beta serum had no effect on fever (ANOVA, P<0.05). LPS-induced suppression of voluntary running and food intake were attenuated in rats receiving anti-IL-6 serum, while the decrease in food intake was totally abolished in rats receiving anti-leptin serum (ANOVA, P<0.05). Injection of anti-TNF-alpha or anti-IL-1beta serum had no effect on LPS-induced sickness behavior. Peripherally released IL-6 and leptin therefore appear to be important in regulating LPS-induced fever and sickness behavior.


Exploring the immunomodulatory role of depot medroxyprogesterones acetate and endogenous progesterone levels in HIV infected and uninfected women.
The aim of this proof of concept study was to determine the effect of depot medroxyprogesterone acetate on host and viral factors in HIV infected and uninfected women. In this study, the gene expression levels for CCL5, CCR5 and CXCR4 was significantly higher in HIV positive women when compared to HIV negative women (p < 0.05). An upregulation of CCR5 and CXCR4 was evident in less than 20% of the HIV infected women and none of the HIV uninfected women. The mean fold change for CCL3 was much higher in HIV uninfected when compared to infected women with a borderline significance (p = 0.062). In HIV uninfected women, the mean fold change in CCL3, CCL4, and CCL5 gene expression was not statistically different between women on DMPA versus women not on hormonal contraception. The proportion of women with an upregulation of CCL4 and CCR5 was higher in HIV infected women on DMPA. There was no association between endogenous progesterone level and chemokines and the HIV-1 receptors. The gene expression levels in the chemokine receptors CCR5 and CXCR4 were significantly higher in the HIV infected women when compared to the women who remained HIV uninfected.


Sympathetic iris function in amyotrophic lateral sclerosis.
Autonomic fibres are generally regarded as being spared in amyotrophic lateral sclerosis. Anatomical studies have cast some doubt upon this hypothesis. The present study describes the pupillary responses to tyramine, a norepinephrine releaser, and to phenylephrine, a directly acting sympathomimetic, in 11 patients with ALS and matched controls. Patients and controls showed a similar sensitivity to sympathomimetic agents, and our results lend some support to the hypothesis that sympathetic functions are not involved in ALS.


Field evaluation of a microgel droplet formulation of Bacillus sphaericus 1593M (Biocide-S) against Anopheles culicifacies and Anopheles subpictus in south India.
A microgel droplet formulation of Bacillus sphaericus 1593M (Biocide-S) was field tested at two different doses viz, 0.22 and 0.43 g/m2 in casuarina pits against a malarial vector Anopheles (Cellia) culicifacies Giles, and An. (Cel.) subpictus Grassi in coconut garden pits in the coastal areas of South India. Both doses significantly reduced the abundance of late instars and pupae of An. culicifacies for 3 and 5 weeks respectively. A significant reduction was recorded in the abundance of late instars and pupae of An. subpictus for 2 and 3 weeks respectively.


Optimization of Productivity and Worker Well-Being by Using a Multi-Objective Optimization Framework.
OCCUPATIONAL APPLICATIONSWorker well-being and overall system performance are important elements in the design of production lines. However, studies of industry practice show that current design tools are unable to consider concurrently both productivity aspects (e.g., line balancing and cycle time) and worker well-being related aspects (e.g., the risk of musculoskeletal disorders). Current practice also fails to account for anthropometric diversity in the workforce and does not use the potential of multi-objective simulation-based optimization techniques. Accordingly, a framework consisting of a workflow and a digital tool was designed to assist in the proactive design of workstations to accommodate worker well-being and productivity. This framework uses state-of-the-art optimization techniques to make it easier and quicker for designers to find successful workplace design solutions. A case study to demonstrate the framework is provided.


Determinants of caregiving burden and quality of life in caregivers of stroke patients.
A large proportion of disabled stroke survivors live at home and are supported by informal caregivers. Identification of determinants of caregiver burden will help to target caregiver interventions. Data on patient, caregiver, and health and social support characteristics were collected prospectively over 1 year in 232 stroke survivors in a randomized trial of caregiver training. The contribution of these variables to caregiver burden score (CBS) and quality of life (QOL) measures at 3 months and 1 year was analyzed using regression models. Stroke patients had a mean age of 74+/-11 years, and 120 (52%) were men. The mean age of caregivers was 65.7+/-12.5 years, 149 (64%) were females, and 116 (50%) had received caregiver training. The mean CBS was 48+/-13 and 38+/-11 (score range of bad to good 88 to 22) and QOL score was 75+/-16 and 75+/-15 (score range of bad to good 0 to 100) at 3 months and 1 year, respectively. CBS and QOL correlated with each other and with patient (age, dependency, and mood), caregiver (age, gender, mood, and training), and support (social services and family networks) variables. Of these, only patient and caregiver emotional status, caregiver age and gender, and participation in caregiver training were independent predictors of either outcome at 3 months. Patient dependency and family support were additional independent predictors at 1 year. Social services support predicted institutionalization but not caregiver outcomes. Advancing age and anxiety in patients and caregivers, high dependency, and poor family support identify caregivers at risk of adverse outcomes, which may be reduced by caregiver training.


A systematic review of literature examining mediators and mechanisms of change in empirically supported treatments for posttraumatic stress disorder.
Despite the availability of empirically supported treatments (ESTs) for posttraumatic stress disorder (PTSD), relatively little is known regarding these treatments' mechanisms of change. This systematic review moves beyond previous reviews by summarizing the findings and reviewing the methodological quality of literature that specifically examined mediators/mechanisms of change in ESTs for PTSD. Studies were included if they were written in English, empirical, peer-reviewed, claimed to study mediators/mechanisms of a recommended PTSD treatment, measured the mediator/mechanism during or before and after treatment, and included a posttreatment PTSD or global outcome (e.g., functioning). PsycINFO and PubMed were searched on October 7, 2022. Two coders screened and coded studies. Sixty-two eligible studies were identified. The most consistent mediator/mechanism was reduction in negative posttraumatic cognitions, followed by between-session extinction and decreased depression. Only 47% of studies measured the mediator/mechanism before the outcome and measured the mediator/mechanism and outcome at least three times, and 32% also used growth curve modeling to establish temporal precedence of change in the mediator/mechanism and outcome. Many of the mediators/mechanisms examined had weak or no empirical support. Results highlight the need for improved methodological rigor in treatment mediator and mechanism research. Implications for clinical care and research are discussed. PROSPERO ID: 248088.


Variations among cultured cells in glutathione peroxidase activity in response to selenite supplementation.
The aim of this study was to devise conditions for manipulation of the activity of selenium-dependent glutathione peroxidase in cell lines by means of variation in culture medium contents of selenite and fetal calf serum. Nine different cell lines were studied. A low glutathione peroxidase activity was, in most cases, obtained by the use of a medium with a low (2%) serum content. Selenite induced in most of the cell lines an increase in glutathione peroxidase activity, with a plateau ranging from 10 nM to 300-1000 nM. Growth-retarding effects of selenite became apparent at 300-2000 nM, showing a large cell line variation. Supplementation with 50-100 nM selenite for 1 week should generally be suitable for maximal glutathione peroxidase induction. The selenium contents of serum batches were highly variable, pointing to the importance of using only one well-defined, preferably low-selenium, batch. The glutathione peroxidase activities varied considerably between cell lines and the selenite-induced increases ranged from negligible to more than 10-fold. The availability of cell lines with such variable responses should be valuable for experiments aimed at evaluating the importance of glutathione peroxidase and selenium compounds independently of glutathione peroxidase for the protection against oxidative insult.


Inhibition of mitogen-activated protein kinase (MAPK) and cyclin-dependent kinase 2 (Cdk2) by platinum(II) phenanthroline complexes.
Inhibition of protein kinases in the fight against disease remains a constant challenge for medicinal chemists, who have screened multitudes of predominantly planar organic scaffolds, natural and synthetic, to identify potent-albeit not always selective-kinase inhibitors. Herein, in an effort to investigate the potential biological utility of metal-based compounds as inhibitors against the cancer-relevant targets mitogen-activated protein kinase and cyclin-dependent kinase 2, we explore various parameters in planar platinum(II) complexes with substituted phenanthroline ligands and aliphatic diamine chelate co-ligands, to identify combinations that yield promising inhibitory activity. The individual ligands' steric requirements as well as their pattern of hydrogen bond donors/acceptors appear to alter inhibitory potency when modulated. The online version of this article (doi:10.1007/s12154-011-0059-5) contains supplementary material, which is available to authorized users.


Pseudocholinesterase-activity reduction during cardiopulmonary bypass: the role of dilutional processes and pharmacological agents.
1. Pseudocholinesterase (ChE) activity is a determinant of the elimination kinetics of several drugs used in anesthesia. The time course of ChE activity was investigated in 16 patients undergoing cardiosurgery for a cardiopulmonary bypass (CPB) in normothermia or hypothermia. 2. The onset of the CPB was accompanied by a decrease in ChE activity (-37%) (P<0.05) and protein concentration (-24%) (P<0.05). The quotient ChE activity/protein concentration was numerically reduced to a smaller extent (-15%) (P>0.05). After the CPB was finished, ChE activity and the protein concentration remained low for the remaining operation time. 3. There was no difference in ChE activity, measured in vitro at 37 degrees C, between the normothermic and hypothermic group (P>0.05). 4. There was no correlation between heparin concentration in serum and reduction of ChE activity in vitro (P>0.05). In vitro, the ChE activity was not affected by either heparin in doses as high as 10,000 U/ml or aprotinin in doses as high as 10,000 U/ml (P>0.05). 5. (1) ChE activity is reduced by CPB mainly by hemodilution and (2) the pharmacological agents used in the present anesthetic technique (heparin, aprotinin, midazolam, fentanyl, propofol and mivacurium) do not inhibit ChE activity at therapeutic serum concentrations.


Intensity of Left Atrial Spontaneous Echo Contrast as a Correlate for Stroke Risk Stratification in Patients with Nonvalvular Atrial Fibrillation.
The intensity of left atrial spontaneous echo contrast (LASEC) by transesophageal echocardiography (TEE) has been proposed as an important variable in the stratification of thromboembolic risk, particularly in patients with nonvalvular atrial fibrillation (NVAF). We hypothesized that the quantification of LASEC by ultrasound will improve its utility in predicting subsequent stroke events in patients with NVAF. Patients (n = 206) with definite NVAF receiving TEE were included for this prospective cohort study. Baseline clinical risk factors of stroke, CHADS2 score and CHA2DS2-Vasc, left atrial thrombus (LAT), the five-grades of LASEC and video intensity (VI) value of LASEC were measured. During 2 years follow-up, 20 patients (9.7%) developed stroke. VI value of LASEC in the patients with stroke was higher compared to patients without stroke (25.30 ± 3.61 vs. 8.65 ± 0.81, p < 0.001). On logistic regression analysis, LAT, qualitative LASEC, graded LASEC, VI value of LASEC and CHADS2 and CHA2DS2-Vasc score were independent predictors of stroke. Among them, the highest area under the curve of receiver operating characteristic (ROC) in predicting stroke was VI value of LASEC (p < 0.05). These results show that quantification of LASEC by VI value is the most favorable predictor of stroke in patients with NVAF, and calls for improving the utility of LASEC in predicting subsequent stroke events.


Astragaloside II enhanced sensitivity of ovarian cancer cells to cisplatin via triggering apoptosis and autophagy.
Cisplatin (DDP) based chemotherapy occurs a reduced therapeutic effect on the later treatment of ovarian cancer (OC) due to DDP resistance. Astragaloside II (ASII), a natural product extracted from Radix Astragali, has shown promising anticancer effects. However, the effects of ASII on OC have not been clarified. In this study, we found that ASII inhibited cell growth and promoted cell apoptosis of DDP-resistant OC cells in vitro and in vivo. Further study showed that ASII downregulated multidrug resistance-related protein MDR1 and cell cycle-related protein Cyclin D1 and PCNA, and also upregulated apoptosis-related protein leaved PRAP and cleaved caspase-3. In addition, ASII induced autophagy, characterized by upregulation of LC3II expression, downregulation of p62 expression, and elevation of LC3 punctuation, may be associated with inhibition of the AKT/mTOR signaling pathway. Moreover, the messenger RNA-sequencing was used to identify potential molecules regulated by ASII. In conclusion, these findings indicated that ASII increased sensitivity of DDP in the treatment of OC.


Estimation of systematic errors of discrete line approximation by triangular tessellation and marching squares algorithm.
This paper presents methods to calculate the length overestimation errors which are being made when approximating a discrete line by edges of triangular tessellation and marching squares algorithm. The maximum error and its average value are 15.47 % and 10.27 % for the triangular tessellation, while for the marching squares approach they are 8.24 % and 5.49 %, respectively. Mathematical calculations were compared with experimental results obtained by the Electron Backscatter Diffraction technique showing their usefulness as correction coefficients to obtain more accurate boundary length estimates.


Molecular-beam study of the water-helium system: features of the isotropic component of the intermolecular interaction and a critical test for the available potential-energy surfaces.
We report molecular-beam measurements of the total integral cross sections for the scattering of water molecules by helium atoms. A combined analysis of the new experimental data together with available differential cross section results has allowed an accurate determination of the isotropic component of the interaction potential for this prototypical system. The potential well shows a depth of 0.265 +/- 0.010 kJ/mol at a distance between He and the center of mass of the water molecule of 0.345 +/- 0.02 nm. An effective isotropic long-range attraction constant C(LR) = (6.3+/-0.3) x 10(-4) kJ mol(-1) nm(-6), including both dispersion and induction contributions, has also been determined. The most recent and accurate ab initio potential-energy surfaces have been tested against these new experimental results.


Allergy in asthma. II. The highly atopic infant and chronic asthma.
The relationship between allergy and asthma in infants and preschool children was investigated. One hundred nine children, median age 2 1/2 years, were examined immunologically by quantitation of serum IgE, RAST testing to 13 allergens, and culture of peripheral blood lymphocytes for spontaneous IgE formation. We examined a cross-section of infants and toddlers to determine whether the severity of asthma is associated with allergy as has been reported in older children with asthma. We identified a group of highly atopic infants and preschool children who have serum IgE at least 10 times the mean + 1 SE for age, multiple positive RASTs with early formation of IgE to inhalant antigens, and circulating B cells that spontaneously form IgE when these are cultured in vitro. Such highly atopic infants and preschool children were statistically more likely to have chronic asthma requiring multiple continuous medication compared to the rest of the population (p less than 0.01).


The normal angiographic sylvian point on the lateral cerebral angiogram.
The angiographic sylvian point (ASP) is one of the most useful landmarks on cerebral angiograms for detecting retrosylvian masses. Although it is suggested to be the halfway point on the clinoparietal line (CPL), its exact normal position has not been defined. The lateral carotid angiograms of 100 consecutive patients from 22 to 65 years of age were used to study the normal ASP in relation to the CPL. Patients with severe neurological deficits or angiographic evidence of hydrocephalus, severe vascular disease or mass lesions were eliminated from this study. In our 100 normals, the normal ASP was within 8 mm above and below the CPL, and in the majority (82%) it was located behind the midpoint of the CPL. It was not situated more than 14.4 mm posterior and never more than 3.1 mm anterior to the midpoint. Application of these normal relationships facilitates detection of small, deep retrosylvian masses occupying the medial portions of the parietal, occipital and temporal lobes.


Errant central line placement.
Clinicians use several tests to confirm proper placement of catheters in central veins. This report describes errant insertion of a catheter intended for the central venous circulation, despite the reassuring results of initial tests to evaluate the insertion procedure.


Alpha7 nicotinic receptor mediated protection against ethanol-induced cytotoxicity in PC12 cells.
Ethanol caused a concentration-dependent loss of PC12 cells over a 24 h interval, accompanied by an increase in intracellular calcium. The specific alpha7 nicotinic receptor partial agonist DMXB attenuated both of these ethanol-induced actions at a concentration (3 microM) found previously to protect against apoptotic and necrotic cell loss. The alpha7 nicotinic receptor antagonist methylylaconitine blocked the neuroprotective action of DMXB when applied with but not 30 min after the agonist. These results indicate that activation of alpha7 nicotinic receptors may be therapeutically useful in preventing ethanol-neurotoxicity.


Systemic infection drives urgent care needs and outcome in adults with long-term neurological conditions.
It is estimated that 1 in 6 people are living with a long-term neurological condition (LTNC). Although it is likely that systemic infections are a common trigger for urgent tertiary care needs in LTNCs, there is a lack of data. Yet this is important since systemic infections are a modifiable risk factor, and hence the motivation for a formal evaluation. We undertook case note review of 155 consecutive unselected adult patients with LTNC receiving urgent care at a tertiary hospital between November and December 2019. Data were collected on presenting symptoms, diagnosis, length of stay, complications, and change in social needs. The most common LTNCs were neurocognitive disorders (n = 68, 44%), cerebrovascular disorders (n = 65, 42%), and epilepsy (n = 19, 12%). Respiratory infections were most common (n = 40, 62.5%), followed by urinary (n = 16, 25%), skin (n = 4, 6%), gastrointestinal (n = 3, 5%) and bone (n = 1, 1.5%). Systemic infection was the trigger for urgent care in 41.3% of patients and in multivariable regression was associated with an increased likelihood of admission (p < 10-5, OR = 7.8, Nagelkerke R2 = 0.37), longer length of stay (p = 0.03, β = 5.91, R2 = 0.06), and death (p = 0.045, OR = 4.3, Nagelkerke R2 = 0.22). Altered mental status was the presenting symptom most frequently associated with infection (p < 10-8, χ2 test). In conclusion, systemic infections are a major trigger of acute tertiary care needs in adults with LTNCs, and play a role in determining clinical outcome. Since systemic infections are preventable or can be treated if identified early, they may represent a modifiable target to improve quality of life, clinical outcomes and health service efficiency.


Letting a Good Crisis Go to Waste.
The widespread implementation of electronic health records (EHRs) was predicated on hopes that they would rapidly improve care, but initial experiences have been disappointing and thought to be a key part of physician dissatisfaction and burnout. The crisis created by EHR implementation is only in part due to EHRs themselves, and might also be viewed as a crisis that has served to surface longstanding problems in healthcare-ones that if grappled with, will lead to more rapidly effective digital transformation.


[Poikilodermic parapsoriasis. Case report and discussion of nomenclature].
A case of a 59 year-old patient with premycotic parapsoriasis lichenoides of a special poikilodermic type is presented. In addition, the formation of multiple bowenoid actinic keratoses and even squamous cell carcinomas on both forearms was apparently favored by the poikilodermic change. An attempt is made to summarize the nomenclature of the parapsoriasis-poikiloderma group of dermatoses.


Printing Ink Wastewater Treatment Using Hydrodynamic Cavitation and Coagulants/Flocculants.
Raw printing ink wastewater (PIW) was treated with various inorganic coagulants and organic flocculants (anionic and cationic polyacrylamides). These processes were also examined as post treatment step following hydrodynamic cavitation. Treatment effectiveness was assessed through color, chemical oxygen demand (COD) and total suspended solids (TSS) removal. The addition of 4500 mg L-1 polyaluminum chloride coagulant in undiluted PIW (COD: 17000 mg L-1) resulted in 99% color removal, 96% COD and TSS removal, after settling for 2 h. The addition of 10 mg L-1 of anionic polyacrylamides in the sample reduced settling time to only 5 min, with concomitant 96-98% removal efficiency. The addition of a 4 min hydrodynamic cavitation pretreatment step reduced coagulant addition by 33%, for the treatment of undiluted PIW (with 10 mg L-1 anionic polyacrylamide), while removals were ranged between 96 and 98%. Economic analysis for the undiluted PIW showed that costs were reduced by ca. 20% with the hydrodynamic cavitation pretreatment step. Moreover, sludge characterization showed the presence of maghemite, aluminum chloride and potassium aluminum silicate. Finally, toxicity tests revealed a significant attenuation of the toxic potential of undiluted PIW, thus indicating the enhanced efficiency of the proposed combined process (hydrodynamic cavitation and coagulation/flocculation).


The protective effect of intratympanic dexamethasone on cisplatin-induced ototoxicity in guinea pigs.
The purpose of this study was to investigate the effectiveness of intratympanic dexamethasone injection as a protection agent against cisplatin-induced ototoxicity. The four groups of guinea pigs were injected as follows: 1) cisplatin, 2) intratympanic dexamethasone, 3) cisplatin following intratympanic dexamethasone, and 4) cisplatin after intratympanic saline. Before and 3 days following injections, the ototoxic effect was measured with distortion product otoacoustic emissions (DPOAEs). The DPOAEs amplitudes and signal-to-noise ratio (SNR) values at 1 to 6 kHz frequencies for group 1 animals after injections significantly decreased over those before injections (P < 0.05). In group 2, there were no significant differences in DPOAE amplitude and SNR values between before and after intratympanic dexamethasone injections (P > 0.05). Considering group 3, there were also no significant differences in DPOAEs amplitudes and SNR values before and after of dexamethasone and cisplatin injections (P > 0.05). Intratympanic dexamethasone injection did not cause any ototoxic effect; in contrast, it might have a significant protective effect after cisplatin injection.


Active pixel sensor matrix based on monolayer MoS2 phototransistor array.
In-sensor processing, which can reduce the energy and hardware burden for many machine vision applications, is currently lacking in state-of-the-art active pixel sensor (APS) technology. Photosensitive and semiconducting two-dimensional (2D) materials can bridge this technology gap by integrating image capture (sense) and image processing (compute) capabilities in a single device. Here, we introduce a 2D APS technology based on a monolayer MoS2 phototransistor array, where each pixel uses a single programmable phototransistor, leading to a substantial reduction in footprint (900 pixels in ∼0.09 cm2) and energy consumption (100s of fJ per pixel). By exploiting gate-tunable persistent photoconductivity, we achieve a responsivity of ∼3.6 × 107 A W-1, specific detectivity of ∼5.6 × 1013 Jones, spectral uniformity, a high dynamic range of ∼80 dB and in-sensor de-noising capabilities. Further, we demonstrate near-ideal yield and uniformity in photoresponse across the 2D APS array.


Insular-limbic dissociation to intra-epidermal electrical Aδ activation: A comparative study with thermo-nociceptive laser stimulation.
Intra-epidermal electrical stimulation (IEES) has been shown to activate selectively Aδ fibers subserving spinothalamic-mediated sensations. Owing to electrically induced highly synchronous afferent volleys, IEES induces Aδ-mediated evoked potentials at nonpainful intensities, contrasting with thermo-nociceptive laser pulses which entail painful pricking sensations. Here, we recorded intracortical responses from sensory and limbic-cognitive regions of human subjects in response to IEE and laser stimuli, in order to test the hypothesis that IEES could dissociate the sensory from nonsensory networks of nociceptive processing. Intracortical evoked potentials were obtained in 11 epileptic patients with stereotactically implanted electrodes in sensory regions receiving spinothalamic afferents (posterior insula), limbic regions receiving spino-parabrachial input (amygdalar nucleus), and high-order affective-cognitive regions (anteromedial frontal cortex, including perigenual anterior cingulate and rostromedial prefrontal areas). Responses in the sensory posterior insula were of similar amplitude and latency to IEE and laser stimuli (after accounting for heat-transduction time of laser), and consistent in both cases with spinothalamic activation. However, responses to IEES in the amygdala and the anteromedial frontal regions were inconsistent and significantly smaller compared to those evoked to the laser stimulation. Thus, IEES can effectively activate the spinothalamic-sensory system with little recruitment of affective-motivational networks, including those triggered by spino-parabrachio-amygdalar projections. The fact that identical sensory responses were associated to either painful or nonpainful percepts underscores that subjective pain perception is not solely dependent on the sensory recruitment, but rather on the combined activation of sensory, limbic and cognitive areas with precise spatiotemporal relations.


[Changes in the relative number of bipolar-like cells in the retina of Pleurodeles waltl as a function of age and as a result of light exposure].
The study of the population of bipolar-like cells (displaced bipolars) was continued in order to establish their role in development and regeneration of the retina in lower vertebrates. The size of the population of these cells was estimated on serial semithin sections in the retina of normal eyes in adult and young newt Pleurodeles waltl, as well as in adult newts subjected to long-term bright illumination. The population of displaced bipolars was significantly increased with reference to all cells of the outer nuclear layer. In young and illuminated animals, their numbers were approximately 1.3 and 1.4 times that in the adult animals not exposed to constant light. The results obtained favor the earlier suggestion of the involvement of the displaced bipolars in growth and restoration of the outer nuclear layer in the retina of newts during development and after trauma.


Health@Home: the work of health information management in the household (HIMH): implications for consumer health informatics (CHI) innovations.
Contemporary health care places enormous health information management demands on laypeople. Insights into their skills and habits complements current developments in consumer health innovations, including personal health records. Using a five-element human factors model of work, health information management in the household (HIMH) is characterized by the tasks completed by individuals within household organizations, using certain tools and technologies in a given physical environment. We conducted a descriptive-exploratory study of the work of HIMH, involving 49 community-dwelling volunteers from a rural Midwestern community. During in-person interviews, we collected data using semistructured questionnaires and photographs of artifacts used for HIMH. The work of HIMH is largely the responsibility of a single individual, primarily engaged in the tasks of acquiring, managing, and organizing a diverse set of health information. Paper-based tools are most common, and residents develop strategies for storing information in the household environment aligned with anticipated use. Affiliative relationships, e.g., parent-child or spousal, within the household serve as the organization that gives rise to health information management practices. Synthesis of these findings led to identification of several storage strategies employed in HIMH. These strategies are labeled "just-in-time," "just-because," "just-in-case," and "just-at-hand," reflecting location of the artifacts of health information and anticipated urgency in the need to retrieve it. Laypeople develop and employ robust, complex strategies for managing health information in the home. Capitalizing on these strategies will complement and extend current consumer health innovations to provide functional support to people who face increasing demands to manage personal health information.


"In vivo" release of endogenous neurotransmitters in cat limbic regions: effect of chlorpromazine and of electrical stimulation.
The effect of chlorpromazine (10 mg/kg i.v.) on the spontaneous release of endogenous dopamine (DA), noradrenaline (NA) and acetylcholine (ACh) within limbic areas perfused by means of the push-pull cannula was investigated in the gallamine-immobilized cat. Chlorpromazine increased the liberation of DA and NA in the nucleus accumbens septi, indicating blockade of the amine receptors. However, the drug did not change the output of ACh from this nucleus nor from ventral and dorsal hippocampal formations which receive a cholinergic input from the septum as indicated by several published findings and by the increased liberation of ACh after electrical stimulation of the homolateral nucleus medialis septi. These results seem to exclude that cholinergic neurons of some limbic areas mediate the effect of the blockade of DA (and of NA) receptors which is possibly involved in the antipsychotic action of neuroleptic drugs.


Thyroid Nodules and Follicular Cell-Derived Thyroid Carcinomas in Children.
Although pediatric thyroid tumors have many similarities to those occurring in adults, significant differences are also recognized. For example, although thyroid nodules in children are much less common than in adults, a higher percentage is malignant. Moreover, while pediatric papillary thyroid carcinoma (PTC) is associated with more advanced disease, death due to disease in children and adolescents is very rare, even when distant metastases are present. Some subtypes of thyroid carcinoma, like diffuse sclerosing variant, are especially common in children and adolescents. Moreover, certain histologic findings, such as a tall cell morphology or increased mitotic activity, may not carry the same prognostic significance in children as in adults. Recent studies exploring the molecular underpinnings of pediatric thyroid carcinoma indicate that while driver alterations of thyroid tumorigenesis in children and adults are essentially the same, they occur at very different frequencies, with translocation-associated tumors (most commonly harboring RET and NTRK fusions) comprising a sizable and distinct group of pediatric PTC. DICER1 mutations, an infrequent mutation in adult thyroid tumors, are relatively frequent in pediatric encapsulated follicular-patterned thyroid tumors (with or without invasion or nuclear features of PTC). Additionally, tumor predisposition syndromes (most notably DICER1 syndrome and PTEN hamartoma tumor syndromes such as Cowden syndrome) should be considered in children with thyroid tumors, especially follicular-patterned thyroid tumors and poorly differentiated thyroid carcinoma. This review will explore the current state of knowledge of thyroid nodules and carcinomas in children and adolescents.


Outpatient Visits Before Ambulatory Care-Sensitive Hospitalization of Children Receiving Medicaid.
Hospitalizations for ambulatory care-sensitive conditions (ACSC) are measured to indicate health care system quality, with the premise that fewer hospitalizations would occur with better preceding outpatient care. Our objectives were to identify outpatient care received in the 7 days preceding acute pediatric hospitalizations and to compare receipt of outpatient care by hospitalization type (ACSC vs non-ACSC). This retrospective observational study used a 10-state database of Medicaid claims to identify outpatient visits within 7 days before acute unplanned hospitalization for children aged 0 to 17 years. We used logistic regression to assess the relationship between hospitalization type and occurrence of a preceding outpatient clinic visit, controlling for patient age, race/ethnicity, type of Medicaid, and complex chronic conditions. Of 254,902 hospitalizations, 28.6% had a preceding outpatient visit. Thirty-five percent of hospitalizations were for ACSC. A greater percentage of ACSC versus non-ACSC hospitalizations had a preceding outpatient visit (31.1% vs 27.3%, P < .001). In multivariable analysis, characteristics associated with a preceding outpatient visit were age <1 versus 13 to 17 years (adjusted odds ratio [aOR] 2.4; 95% confidence interval [CI] 2.3-2.5), ≥2 vs 0 complex chronic conditions (aOR 1.9; 95% CI 1.8-2.0), Medicaid managed care versus fee for service (aOR 1.2; 95% CI 1.2-1.3), and ACSC versus non-ACSC hospitalization (aOR 1.2; 95% CI 1.1-1.2). Although receipt of outpatient care was modestly higher in children hospitalized with an ACSC, most hospitalized children did not receive preceding outpatient care. Further investigation is needed to assess why such a large proportion of children do not receive outpatient care before acute unplanned hospitalization, especially for ACSC.


Prognostic impact of marginal resection for patients with solitary hepatocellular carcinoma: evidence from 570 hepatectomies.
During resection of a hepatocellular carcinoma, surgeons encounter occasionally a situation where marginal resection is inevitable because of a close association between the hepatocellular carcinoma and major vasculature and/or underlying impaired liver function. We investigated the impact of marginal resection on recurrence-free survival after a resection of a solitary hepatocellular carcinoma. The data of 570 patients who underwent macroscopically curative hepatectomy for a solitary hepatocellular carcinoma in our institution between 1990 and 2007 were analyzed. Marginal resection and non-marginal resection were defined as a cancer-negative surgical margin of ≤ 1 mm and a surgical margin of >1 mm, respectively. The macroscopic appearance of the hepatocellular carcinoma was classified as the simple nodular type or non-simple nodular type based on the classification of the Liver Cancer Study Group of Japan, and patients were categorized into 4 groups: group A, simple nodular type with cirrhosis; group B, simple nodular type without cirrhosis; group C, non-simple nodular type with cirrhosis; and group D, non-simple nodular type without cirrhosis. The surgical margins were diagnosed as cancer-positive in 31 patients, as marginal resection in 165 patients, and as non-marginal resection in 374 patients. The marginal resection group showed a better recurrence-free survival than the positive surgical margin group (P = .001), and also a worse recurrence-free survival than the non-marginal resection group (P = .003). In groups A, B, and C, the recurrence-free survival rates were similar between marginal resection and non-marginal resection patients (P = .458), while in group D, marginal resection was a significant poor prognostic factor of recurrence-free survival in both univariate and multivariate analyses. Marginal resection is acceptable in group A, B, and C patients, because it did not negatively affect postoperative recurrence-free survival.


Body temperature patterns in two syntopic elephant shrew species during winter.
We measured body temperature (T(b)) in free-ranging individuals of two species of elephant shrews, namely western rock elephant shrews (Elephantulus rupestris) and Cape rock elephant shrews (E. edwardii), during winter in a winter-rainfall region of western South Africa. These syntopic species have similar ecologies and morphologies and thus potential for large overlaps in diet and habitat use. Unexpectedly, they displayed different T(b) patterns. Western rock elephant shrews were heterothermic, with all individuals decreasing T(b) below 30°C on at least 34% of nights. The level of heterothermy expressed was similar to other species traditionally defined as daily heterotherms and was inversely related to T(a), as is commonly seen in small heterothermic endotherms. In contrast, Cape rock elephant shrews rarely allowed their T(b) to decrease below 30°C. The level of heterothermy was similar to species traditionally defined as homeotherms and there was no relationship between the level of heterothermy expressed and T(a). In both species, the minimum daily T(b) was recorded almost exclusively at night, often shortly before sunrise, although in some individuals minimum T(b) occasionally occurred during the day. The interspecific variation in T(b) patterns among Elephantulus species recorded to date reiterates the importance of ecological determinants of heterothermy that interact with factors such as body mass and phylogeny.


A case of late-onset right ventricular failure after implantation of a continuous-flow left ventricular assist device.
Postoperative right ventricular failure is usually apparent perioperatively or soon after left ventricular assist device insertion. Here, we report a case complicated by right ventricular failure that manifested 3 weeks after HeartMate II implantation. This case is also unique because the postoperative right ventricular failure was progressive over the years. We discuss how the smaller size of the left ventricle and untreated tricuspid regurgitation contributed to the development of right ventricular failure in this case.


Altered urinary excretion of human kininase activity in acute myocardial infarction.
This study concerns the determination of levels of human urinary kininase excretion in acute myocardial infarction (AMI). The results obtained by a biological method show that there is a significant reduction of the enzymatic activity in patients affected by AMI in comparison with normals (6.4 +/- 0.4 ng of destroyed bradykinin/min. versus 164.4 +/- 31.4 ng; P less than 0.001), while urinary kallikrein excretion was close to normal values.


Vitamin D Receptor Genetic Polymorphism Is Significantly Associated with Risk of Type 2 Diabetes Mellitus in Chinese Han Population.
We investigated the effect of vitamin D receptor (VDR) gene polymorphism on the risk of type 2 diabetes mellitus (T2DM) in a Chinese Han population. Three tagSNPs (rs11574129, rs2228570 and rs739837) were genotyped using TaqMan assays in a case-control study including 669 cases with T2DM, 1084 individuals with impaired fasting glucose (IFG) and 1,961 controls with normal fasting glucose. Multiple logistic regression was applied to analyze the association of SNPs and the risk of diabetes by adjusting for covariates including age, sex, body mass index (BMI) and smoking. General linear model (GLM) was applied to compare fasting blood glucose levels between genotypes and adjusted for confounding factors. The results showed that rs739837 was significantly associated with increased risk of T2DM in additive model (OR = 1.166, 95% CI 1.017-1.337, p = 0.028) and dominant (OR = 1.166, 95% CI 1.017-1.337, p = 0.002) model. Stratified analysis showed that rs739837 and rs2228570 were, respectively, correlated with T2DM in females and males. Significant associations were found between three SNPs and T2DM in the population <55 years of age. SNPs (rs739837, rs11574129) showed significant associations with T2DM in the smoking population. Quantitative trait analysis indicated that the CC group of rs2228570 has lower fasting glucose than TT/TC genotype group in controls. This study provides further evidence that rs739837 in the VDR gene is associated with increased risk of T2DM in a Chinese Han population.


Automated pericardial fat quantification from coronary magnetic resonance angiography: feasibility study.
Pericardial fat volume (PFV) is emerging as an important parameter for cardiovascular risk stratification. We propose a hybrid approach for automated PFV quantification from water/fat-resolved whole-heart noncontrast coronary magnetic resonance angiography (MRA). Ten coronary MRA datasets were acquired. Image reconstruction and phase-based water-fat separation were conducted offline. Our proposed algorithm first roughly segments the heart region on the original image using a simplified atlas-based segmentation with four cases in the atlas. To get exact boundaries of pericardial fat, a three-dimensional graph-based segmentation is used to generate fat and nonfat components on the fat-only image. The algorithm then selects the components that represent pericardial fat. We validated the quantification results on the remaining six subjects and compared them with manual quantifications by an expert reader. The PFV quantified by our algorithm was [Formula: see text], compared to [Formula: see text] by the expert reader, which were not significantly different ([Formula: see text]) and showed excellent correlation ([Formula: see text],[Formula: see text]). The mean absolute difference in PFV between the algorithm and the expert reader was [Formula: see text]. The mean value of the paired differences was [Formula: see text] (95% confidence interval: [Formula: see text] to 6.21). The mean Dice coefficient of pericardial fat voxels was [Formula: see text]. Our approach may potentially be applied in a clinical setting, allowing for accurate magnetic resonance imaging (MRI)-based PFV quantification without tedious manual tracing.


Cytochrome b of fish mitochondria is strongly resistant to funiculosin, a powerful inhibitor of respiration.
We report here some unusual properties of ubiquinol: cytochrome c reductase of eel and other fish mitochondria. The turnover rate of the reductase is clearly higher than in mammalian mitochondria and the binding constant for ubiquinone seems to be larger than in other vertebrates. Additionally, the reductase activity of fish mitochondria is resistant to some powerful inhibitors that bind to cytochrome b, in particular to funiculosin. After sequencing most of the gene of eel cytochrome b and comparing the deduced amino acid sequence with that of other fish and animals, we hypothesize that the decreased binding of funiculosin could be due to a few amino acid replacements in the third and fourth transmembrane helix of the protein. In particular, the presence of methionine instead of alanine at position 125 seems to be largely responsible for the strong resistance to funiculosin and also to the partial resistance to myxothiazol in all fish mitochondria. Correlations between some residue substitutions in cytochrome b and the different effects of funiculosin in different species are also considered.


Can various complete blood count parameters helpful in preoperative diagnosis of adnexal torsion?
Adnexal torsion is an important gynecological emergency due to nonfrequent but possible adverse reproductive outcomes. There is no specific laboratory marker to support the preoperative diagnosis or that can be used clinically. The aim of this study was to investigate the diagnostic values of platelet, neutrophil, lymphocyte, and red cell markers as an early indicator of ovarian torsion. This retrospective study included 28 female patients who were treated surgically for adnexal torsion between August 2010 and July 2020, and 29 control group women. The demographic data and routine hematological values of patients were compared for adnexal torsion prediction. There were no differences between the groups in terms of the platelet count, platelet distribution width, red cell distribution width, and mean platelet volume values, and there were no differences in the demographic data. Statistical differences were found among white blood cell, hemoglobin, hematocrit, neutrophil and lymphocyte counts, neutrophil/lymphocyte ratio, and platelet/lymphocyte ratio, and 81.5% sensitivity and 82.1% specificity were identified for neutrophil/lymphocyte ratio 2.45 (area under the curve AUC 0.892; 95%CI 0.808-0.975; p<0.001). Odds ratio for neutrophil/lymphocyte ratio was 2.62 (95%CI 0.861-7.940, p=0.029). According to the regression analysis, neutrophil/lymphocyte ratio was found to be the most beneficial among all blood count parameters for the pre-diagnosis of AT.


Therapeutic Effect of MK2 Inhibitor on Experimental Murine Dry Eye.
To investigate the role of mitogen-activated protein kinase-activated protein kinase-2 (MK2) in ocular surface damage of dry eye. MK2 inhibition was performed in mice subjected to desiccating stress (DS) by topical application of MK2 inhibitor (MK2i) or vehicle eye drops. The total and phosphorylated MK2 in conjunctiva were detected by Western blot. The phenol red cotton test was used to measure tear production, and Oregon green dextran staining was performed to assess corneal epithelial barrier function. PAS staining was used to quantify conjunctival goblet cells. Immunofluorescent staining and quantitative RT-PCR were used to assess the expression of matrix metalloproteinase (MMP)-3 and -9 in corneal epithelium. Apoptosis in ocular surface was assessed by TUNEL and immunofluorescent staining for activated caspase-3 and -8. Inflammation was evaluated by CD4+ T-cell infiltration and production of T helper (Th) cytokines, including IFN-γ, IL-13, and IL-17A in conjunctiva. DS promoted MK2 activation in conjunctiva. Compared with vehicle control mice, MK2i-treated mice showed increased tear production, decreased goblet cell loss, and improved corneal barrier function. Topical MK2 inhibition decreased the expression of MMP-3 and -9 in corneal epithelium, and suppressed cell apoptosis in ocular surface under DS. Topical MK2 inhibition decreased CD4+ T-cell infiltration, with decreased production of IFN-γ and IL-17A and increased production of IL-13 in conjunctiva. Topical MK2 inhibition effectively alleviated ocular surface damage via suppressing cell apoptosis and CD4+ T-cell-mediated inflammation in ocular surface of dry eye.


Helicobacter pylori infection and oncogene expressions in gastric carcinoma and its precursor lesions.
Although it is fairly well accepted that Helicobacter pylori infection plays a significant role in causing gastric cancer, the exact mechanisms involved in its pathogenesis are unclear. We have examined the relationship between H. pylori infection and oncogene expression in different stages of disease progression from precursor lesions to gastric carcinoma. We used Diff-Quik stain to diagnose H. pylori infection and immunohistochemical stains against c-erbB-2, p53, ras, c-myc, and bcl-2 to determine expression of oncogenes. H. pylori infection was found in all cases of chronic gastritis, atrophic gastritis, intestinal metaplasia, and early gastric carcinoma, and in 16 of 30 (53%) cases of advanced gastric carcinoma. Overexpression of c-erbB-2 was found in 2 (7%) cases of advanced gastric carcinoma, which were H. pylori negative. Suppressor gene, p53, was overexpressed in 3 (30%) cases of intestinal metaplasia, 2 (33%) cases of early gastric carcinoma, and 18 (60%) cases of advanced gastric carcinoma. Of these 18 p53-positive advanced gastric cancer cases, 11 (61%) were H. pylori positive. Expression of ras p21 was found in 4 (40%) cases of H. pylori-negative normal mucosa, 10 (100%) cases of chronic gastritis, 1 (10%) case of atrophic mucosa, 6 (60%) cases of intestinal metaplasia, 2 (33%) cases of nonneoplastic mucosa adjacent to early gastric carcinoma, and 7 (23%) nonneoplastic mucosa adjacent to advanced gastric carcinoma, all of which showed H. pylori. No evidence of expression of either c-myc or bcl-2 was detected in any of the above-mentioned samples. The data suggest that H. pylori infection may increase expression of ras p21 proteins and induce p53 suppressor gene mutation early in the process of gastric carcinogenesis.


Seek and you shall find: An assessment of the influence of the analytical methodologies on pesticide occurrences in honey bee-collected pollen with a systematic review.
Honey bee mortality and colony losses have been reported worldwide. Although this phenomenon is caused by a combination of factors, agrochemicals have received special attention due to their potential effects on bees. In agricultural and urban environments bees are exposed to several compounds that may interact in unexpected ways, but information on the extent of pesticide exposure remains unclear. Several monitoring studies have been conducted to evaluate the field-realistic exposure of bees to pesticides after their release on the market. However, their outputs are difficult to compare and harmonize due to differences in the analytical methodologies and the sampling protocols (e.g. number of screened compounds and analysed samples, and detection limits (LODs)). Here, we hypothesize that the analytical methodologies used in the monitoring studies may strongly affect the pesticide occurrences in pollen underestimating the real pesticide exposure. By mean of a systematic literature review, we have collected relevant information on pesticide contaminations in the honey bee-collected pollen. Our findings showed that the pesticide occurrences were associated with the analytical methodologies and the real pesticide exposure has likely been underestimated in some monitoring studies. For four highly toxic compounds, the LOD used in these monitoring studies exceeded the doses that cause toxic effects on honey bees. We recommend that, especially for the highly toxic compounds, the LODs used in the monitoring studies should be low enough to exclude lethal or sublethal effects on bees and avoid "false negative" samples.


Molecular characterization, expression pattern, and ligand-binding property of three odorant binding protein genes from Dendrolimus tabulaeformis.
Odorant binding proteins (OBPs) play important roles in insect olfactory processes. The Chinese pine caterpillar moth, Dendrolimus tabulaeformis (Lepidoptera, Lasiocampidae) is a serious economic pest in China, and the pheromones of this species have been identified to monitor their presence. However, the molecular mechanisms by which D. tabulaeformis perceive pheromones and host volatiles remain unknown. In this study, we identified and characterized three new OBPs, including one pheromone binding protein (PBP1) and two general odor binding proteins (GOBPs), from antennal cDNA of D. tabulaeformis. The deduced amino acid sequences of DtabPBP1, DtabGOBP1, and DtabGOBP2 revealed mature proteins of 140, 147, and 140 amino acids, respectively. Each has six cysteine residues in conserved positions relative to other known OBPs. Amino-acid alignments indicated that the two GOBPs are more conserved (DtabGOBP1 is 52.9-67.4 % identical to orthologs from other Lepidoptera, and DtabGOBP2 is 55.2-81.8 % identical) than the PBP (32.5-46.0 %). Real-time PCR indicated tissue- and sex-specific expression patterns of the three genes. DtabPBP1 was mainly expressed in the antennae of males, whereas female antennae had only 1.09 % the expression in male antennae. Both DtabGOBP1 and DtabGOBP2 were more highly expressed in antennae than in other tissues, while DtabGOBP1 was more abundant in male antennae and DtabGOBP2 in female antennae. In addition, the binding specificities of the three proteins were investigated, and all three OBPs exhibited high binding affinities for the pheromone component (5Z,7E)-5,7-dodecadien-1-yl propionate (Z5,E7-12:OPr). This suggests a role in binding pheromone for GOBPs, as well as PBP1, in D. tabulaeformis.