Sublingual vs. intranasal dexmedetomidine sedation for flexible fiberoptic bronchoscopy procedure: a retrospective comparative study.
Flexible fiberoptic bronchoscopy (FOB) is an often-employed invasive method in diagnosing, staging, and treating lung diseases. Conventional sedative agents facilitate this process. Dexmedetomidine (DM) has low side effects and is easy to administer for trans-mucosal absorption. This study aimed to investigate trans-mucosal DM used with local anesthesia during the FOB procedure. Fifty-nine cases were retrospectively analyzed who had undergone diagnostic flexible fiberoptic bronchoscopy (FOB) in our clinic between September 2016 and September 2019. The two methods (Group 1: Sublingual, and Group 2: Intranasal) employed during the FOB procedure for the local anesthesia were compared. Fifty-nine patients were included in the study, wherein forty-six were males (77.9%), and thirteen (22.1%) females had a mean age of 58.02±8.7 years (range: 39-72 years). Thirty-three patients were in Group 1 (Sublingual) and 26 in Group 2 (Intranasal). No significant differences were there between groups regarding age, gender, body mass index, or ASA physical status. Modified Aldrete Score >9 was significant to reach with time as a correlation between operator and patient satisfaction. Sedation scores for groups at 1st, 9th, 12th, and 15th min were similar. Excessive coughing was observed in two (7.7%) patients of Group 2 but in none of Group 1 (p=0.105). Patients in both groups had no complaints of swallowing, excessive body movement, or lower oxygen saturation during examination (p>0.05). There were no complications (hypotension, bradycardia, respiratory depression, allergy, permanent amnesia, nausea, and vomiting) observed in patients. Our study results revealed that easily administered trans-mucosal dexmedetomidine sedation is safely applied during flexible fiberoptic bronchoscopy for adequate sedation, high satisfaction, and low complication rates with no significant difference in sublingual or intranasal administration.


Alternative approaches to external chest compression.
The finding that blood flow during external chest compression may be due to increased intrathoracic pressure, and the subsequent reporting of increased carotid blood flow with simultaneous ventilation and chest compression or with abdominal binding during CPR ignited a flurry of investigations into alternative approaches to CPR. A number of alterations of the conventional CPR technique were proposed, many resulting in improved hemodynamics when compared with standard CPR techniques in the same subject. However, some of the proposed methods increased cerebral blood flow but decreased myocardial perfusion. Others improved systolic pressures but decreased vital organ blood flow. More importantly, most studies with survival as an end point failed to show a benefit when alternative approaches to CPR were used. Therefore, it is unlikely that there will be significant changes in the recommendations for the use of adjuncts during CPR. Not all studies support the conclusion that blood flow during closed-chest compression is secondary to increased intrathoracic pressure. It is probable that in man there is a spectrum. In some individuals the predominant mechanism of blood flow during CPR may be cardiac and/or vascular compression, and in others flow may be secondary to an increased intrathoracic pressure.


Multivisceral Resection for Locally Advanced Rectal Cancer: Prognostic Factors Influencing Outcome.
To assess outcome in patients with locally advanced rectal cancer undergoing multivisceral resection. Retrospective study of 30 consecutive patients (mean age 67.8 years) with primary locally advanced rectal cancer undergoing en bloc multivisceral resection of the organs involved with curative intent between 1998 and 2010. Overall survival, local and distal recurrence, and disease-free survival were analyzed by the Kaplan-Meier method. Risk factors for clinical outcome were obtained using a Cox multivariate model. Postoperative complications occurred in 76.7% of patients and the in-hospital mortality rate was 10%. The median follow-up was 28.8 months. A total of 19 patients died at follow-up. Of the 11 patients who were alive, 7 were free of disease. In the multivariate analysis, lymph node involvement, stage II, and lymph vascular invasion were significantly associated with survival, and stage III showed a strong trend towards significance. Suture dehiscence (peritonitis and intra-abdominal abscess) showed a significant trend towards a higher local recurrence. Lymph vascular invasion was associated with a higher distant recurrence. Lymph node involvement was associated with worse survival, whereas stage II and absence of lymph vascular invasion were associated with a better survival. Lymph vascular invasion was associated with a higher distant recurrence.


Identification of PDL-1 as a novel biomarker of sensitizer exposure in dendritic-like cells.
The development of novel in vitro methods to assess risks of allergic sensitization are essential in reducing animal testing whilst maintaining consumer safety. The main research objectives of this study were to identify novel biomarkers to assess the sensitization predictability of chemicals. Phenotypic and cytokine responses of moDCs and MUTZ-3 cells were investigated following application of contact sensitizers; dinitrochlorobenzene (DNCB), cinnamaldehyde (Cin), eugenol (E), isoeugenol (IE), P-phenylenediamine (PPD) and non-sensitizers; salicyclic acid (SA) and sodium lauryl sulphate (SLS). CD86 was up-regulated on MUTZ-3 cells in response to DNCB, Cin and PPD, however, moDCs only modulated CD86 in response to DNCB and E. PDL-1 (Programmed death receptor ligand-1) proved a promising sensitization biomarker in MUTZ-3 cells where up-regulation occurred in response to DNCB, Cin, IE and PPD. Additionally, moDC-expressed PDL-1 was modulated in response to Cin, IE and E thus demonstrating improved sensitizer predictability when compared with CD86. MCP-1 and RANTES were identified as biomarkers of DNCB exposure but MCP-1 did not show any change in expression above controls for the other sensitizers investigated. However, RANTES was increased in MUTZ-3 cells by both DNCB and Cin. Our findings highlight novel biomarkers which, in MUTZ-3 cells, could be taken forward within a multiple biomarker in vitro assay ensuring strong and reliable predictability.


The Spontaneous Counterfactual Inference Task: Misremembering What Might Have Been.
Counterfactuals, thoughts about "what might have been," play an important role in causal judgment, emotion, and motivation, and spontaneously arise during daily life. However, current methods to measure spontaneous counterfactual thinking are cumbersome and subjective. The current research adapts a paradigm from the Spontaneous Trait Inference literature to develop the Spontaneous Counterfactual Inference measure (SCFI), which uses false recognition of counterfactual statements as a measure of spontaneous counterfactual thought. Studies 1a and 1b demonstrate that the SCFI is sensitive to precursors of counterfactual thinking: norm violation and counterfactual closeness. Study 2 demonstrates that the SCFI converges with the generation of counterfactual statements in an open-ended writing task. The SCFI also predicts two important consequences of counterfactual thought, blame (Study 3), and intention endorsement (Study 4). The SCFI thus offers a new tool for researchers interested in counterfactual thinking.


Lumbosacral disc protrusion: a case report.
A negative myelogram but a positive CT for an L5 disc protrusion is presented. Five months of medical care preceded chiropractic care; the insurance company involvement in a case where treatment mode is changed from usual orthodox medical procedures of epidural steroid injection and physical therapy to chiropractic distraction manipulation is detailed. Finally the clinical outcome of the case is provided.


Massive post-infarction ventricular septal rupture complicaing cardiogenic shock with long term veno-arterial extracorporeal membrane oxygenation support.
Ventricular septal rupture (VSR) following acute myocardial infarction (AMI) is a rare but serious complication often causing cardiogenic shock (CS). The timing of surgery is a difficult problem for surgeons because of high mortality and surgical complexity. We present a case of successful use of extracorporeal membrane oxygenation (ECMO) for maintaining haemodynamic stability preoperative and delaying surgical repair of VSR patient in severe CS. A 57-year-old man with AMI complicated by severe CS due to an massive VSR. Emergency surgery was considered a too high mortality risk. The patient was implanted with a percutaneous veno-arterial ECMO (VA-ECMO) system as a bridge to surgery for stabilizing general condition. On the 31th day after ECMO implantation, the ventricular septal defect was successfully repaired and weaning from the ECMO. This case study illustrates that it may be considered to use long term ECMO preoperative to delayed surgery which leads to higher survival in cases of massive VSR patient after AMI in hemodynamically compromised patients. Still the optimal duration of mechanical circulatory support and the optimal timing for surgery need more research to define. This case indicates the feasibility of preoperative using of a long term VA-ECMO as a bridge to surgical repair of VSR patient after AMI in severe CS. The optimal duration of mechanical circulatory support and the optimal timing for surgery still require further investigation.


Praziquantel and the benzodiazepine Ro 11-3128 do not compete for the same binding sites in schistosomes.
The benzodiazepine Ro 11-3128 (methyl-clonazepam) presents several similarities with praziquantel with regard to its anti-schistosomal mode of action, since both drugs cause spastic paralysis, calcium influx and tegumental disruption in the parasites. In order to know whether the two compounds share the same binding sites in the schistosomes, we performed in vivo and in vitro competition experiments. We took advantage of the fact that Ro 11-3128 is active against immature Schistosoma mansoni (whereas praziquantel is inactive), and praziquantel is active against S. japonicum (which is insensitive to Ro 11-3128). An excess of praziquantel did not inhibit the activity of Ro 11-3128 against immature S. mansoni and an excess of Ro 11-3128 did not inhibit the activity of praziquantel against S. japonicum, suggesting that the schistosome binding sites of the two drugs are different. On the other hand, cytochalasin D, an agent known to perturb--among other things--calcium channel function, was capable of inhibiting the schistosomicidal activity of both praziquantel and Ro 11-3128, thus adding another element of similarity between the two anti-schistosomal agents. A similar, albeit partial, inhibition of the schistosomicidal activity of the two drugs was exerted by some of the classical calcium channel blockers. Taken together, these results suggest that praziquantel and Ro 11-3128, although binding to different schistosome receptor sites, may use the same basic anti-schistosomal effector mechanisms.


Communication and complexity in a GRN-based multicellular system for graph colouring.
Artificial Genetic Regulatory Networks (GRNs) are interesting control models through their simplicity and versatility. They can be easily implemented, evolved and modified, and their similarity to their biological counterparts makes them interesting for simulations of life-like systems as well. These aspects suggest they may be perfect control systems for distributed computing in diverse situations, but to be usable for such applications the computational power and evolvability of GRNs need to be studied. In this research we propose a simple distributed system implementing GRNs to solve the well known NP-complete graph colouring problem. Every node (cell) of the graph to be coloured is controlled by an instance of the same GRN. All the cells communicate directly with their immediate neighbours in the graph so as to set up a good colouring. The quality of this colouring directs the evolution of the GRNs using a genetic algorithm. We then observe the quality of the colouring for two different graphs according to different communication protocols and the number of different proteins in the cell (a measure for the possible complexity of a GRN). Those two points, being the main scalability issues that any computational paradigm raises, will then be discussed.


Door-to-puncture: a practical metric for capturing and enhancing system processes associated with endovascular stroke care, preliminary results from the rapid reperfusion registry.
In 2011, the Brain Attack Coalition proposed door-to-treatment times of 2 hours as a benchmark for patients undergoing intra-arterial therapy (IAT). We designed the Rapid Reperfusion Registry to capture the percentage of stroke patients who meet the target and its impact on outcomes. This is a retrospective analysis of anterior circulation patients treated with IAT within 9 hours of symptom onset. Data was collected from December 31, 2011 to December 31, 2012 at 2 centers and from July 1, 2012 to December 31, 2012 at 7 centers. Short "Door-to-Puncture" (D2P) time was hypothesized to be associated with good patient outcomes. A total of 478 patients with a mean age of 68±14 years and median National Institutes of Health Stroke Scale (NIHSS) of 18 (IQR 14 to 21) were analyzed. The median times for IAT delivery were 234 minutes (IQR 163 to 304) for "last known normal-to-groin puncture" time (LKN-to-GP) and 112 minutes (IQR 68 to 176) for D2P time. The overall good outcome rate was 39.7% for the entire cohort. In a multivariable model adjusting for age, NIHSS, hypertension, diabetes, reperfusion status, and symptomatic hemorrhage, both short LKN-to-GP (OR 0.996; 95% CI [0.993 to 0.998]; P<0.001) and short D2P times (OR 0.993, 95% CI [0.990 to 0.996]; P<0.001) were associated with good outcomes. Only 52% of all patients in the registry achieved the targeted D2P time of 2 hours. The time interval of D2P presents a clinically relevant time frame by which system processes can be targeted to streamline the delivery of IAT care nationally. At present, there is much opportunity to enhance outcomes through reducing D2P.


Causes of variation among rice models in yield response to CO2 examined with Free-Air CO2 Enrichment and growth chamber experiments.
The CO2 fertilization effect is a major source of uncertainty in crop models for future yield forecasts, but coordinated efforts to determine the mechanisms of this uncertainty have been lacking. Here, we studied causes of uncertainty among 16 crop models in predicting rice yield in response to elevated [CO2] (E-[CO2]) by comparison to free-air CO2 enrichment (FACE) and chamber experiments. The model ensemble reproduced the experimental results well. However, yield prediction in response to E-[CO2] varied significantly among the rice models. The variation was not random: models that overestimated at one experiment simulated greater yield enhancements at the others. The variation was not associated with model structure or magnitude of photosynthetic response to E-[CO2] but was significantly associated with the predictions of leaf area. This suggests that modelled secondary effects of E-[CO2] on morphological development, primarily leaf area, are the sources of model uncertainty. Rice morphological development is conservative to carbon acquisition. Uncertainty will be reduced by incorporating this conservative nature of the morphological response to E-[CO2] into the models. Nitrogen levels, particularly under limited situations, make the prediction more uncertain. Improving models to account for [CO2] × N interactions is necessary to better evaluate management practices under climate change.


An Efficient Skin Cancer Diagnostic System Using Bendlet Transform and Support Vector Machine.
Skin is the outermost and largest organ of the human body that protects us from the external agents. Among the various types of diseases affecting the skin, melanoma (skin cancer) is the most dangerous and deadliest disease. Though it is one of the dangerous forms of cancer, it has a high survival rate if and only if it is diagnosed at the earliest. In this study, skin cancer classification (SCC) system is developed using dermoscopic images. It is considered as a classification problem with the help of Bendlet Transform (BT) as features and Support Vector Machine (SVM) as a classifier. First, the unwanted information's such as hair and noises are removed using median filtering approach. Then, directional representation based feature extraction system that precisely classifies curvature, location and orientation is employed. Finally, two SVM classifiers are designed for the classification. The performance of the SCC system based on Bendlet is superior to other image representation systems such as Wavelets, Curvelets, Contourlets and Shearlets.


Photoaffinity-labelling of the calcium-channel-associated 1,4-dihydropyridine and phenylalkylamine receptor in guinea-pig hippocampus. A 195 kDa polypeptide carries both drug receptors and has similarities to the alpha 1 subunit of the purified skeletal-muscle calcium channel.
This study identifies calcium-antagonist-receptor-carrying polypeptides of calcium channels in guinea-pig hippocampus membranes. The arylazide ligands (-)-[3H]azidopine and [N-methyl-3H]LU49888 [(-)-5-[(3-azidophenethyl) [N-methyl-3H]methylamino]-2-(3,4,5-trimethoxyphenyl-2- isopropylvaleronitrile] were used to selectively label 1,4-dihydropyridine and phenylalkylamine receptors respectively. In the absence of u.v. light, both ligands reversibly bound to a single class of high-affinity receptors with a calcium-channel-typical pharmacological profile. [N-methyl-3H]LU49888 bound to the extent of 849 +/- 188 fmol/mg of protein (mean +/- S.D., n = 3) with a dissociation constant (Kd) of 1.4 +/- 0.3 nM. Under identical assay conditions (-)-[3H]azidopine labelled to the extent of 562 +/- 132 fmol/mg of protein with a Kd of 0.096 +/- 0.024 nM. After u.v. irradiation of the [N-methyl-3H]LU49888- and (-)-[3H]azidopine-labelled membranes, both photo-affinity probes were found to be incorporated specifically into a 190-195 kDa band as shown by SDS/polyacrylamide-gel electrophoresis (SDS/PAGE). Photoincorporation occurred with a protection profile identical with that produced by reversible binding-inhibition. [N-methyl-3H]LU49888, but not (-)-[3H]-azidopine, specifically labelled an additional 265 kDa band. Both photolabelled bands had an identical electrophoretic mobility on SDS/PAGE, irrespective of pretreatment either with 10 mM-N-ethylmaleimide or 10 mM-dithiothreitol. The electrophoretic properties of the 195 kDa polypeptide and the lability of receptor-incorporated (-)-[3H]azidopine to nucleophilic agents resemble those of the previously described drug-receptor-carrying alpha 1 subunit of the purified skeletal-muscle calcium channel. The data suggest that this polypeptide carries both the high-affinity 1,4-dihydropyridine as well as the phenylalkylamine receptor of neuronal calcium channels in guinea-pig hippocampus and is a component of the L-type calcium channel.


High-fat feeding alters both basal and stress-induced hypothalamic-pituitary-adrenal activity in the rat.
High-fat feeding induces insulin resistance and increases the risk for the development of diabetes and coronary artery disease. Glucocorticoids exacerbate this hyperinsulinemic state, rendering an individual at further risk for chronic disease. The present studies were undertaken to determine whether dietary fat-induced increases in corticosterone (B) reflect alterations in the regulatory components of the hypothalamic-pituitary-adrenal (HPA) axis. Adult male rats were maintained on a high-fat (20%) or control (4%) diet for varying periods of time. Marked elevations in light-phase spontaneous basal B levels were evident as early as 7 days after fat diet onset, and B concentrations remained significantly elevated up to 21 days after fat diet onset compared with controls. In contrast, there were no significant effects on any parameters of spontaneous growth hormone secretory profiles, thus providing support for the specificity of the effects on the HPA axis. In a second study, all groups of rats fed the high-fat diet for 1, 9, or 12 wk exhibited significantly elevated levels of plasma adrenocorticotropic hormone, B, fatty acid, and glucose before, during, and/or at 20, 60, and/or 120 min after the termination of a restraint stress. Furthermore 12-wk fat-fed animals showed a significant resistance to insulin compared with normally fed controls. There were no differences in negative feedback efficacy in high-fat-fed rats vs. controls. Taken together, these results suggest that dietary fat intake acts as a background form of chronic stress, elevating basal B levels and enhancing HPA responses to stress.


Investigation of the Performance of TDoA-Based Localization Over LoRaWAN in Theory and Practice.
The paper deals with the localization in a low-power wide-area-network (LPWAN) operating long-range wide-area-network (LoRaWAN) technology. The LoRaWAN is, today, one of the most widely used connectivity-enabling technologies for the battery-powered smart devices employed in a broad range of applications. Many of these applications either require or can benefit from the availability of geolocation information. The use of global positioning system (GPS) technology is restrained by the bad propagation of the signal when the device is hidden indoors, and by energy consumption such a receiver would require. Therefore, this paper focuses on an alternative solution implying the use of the information readily available in the LoRaWAN network and application of the time difference of arrival (TDoA) method for the passive geolocation of end-devices in the network. First, the limits of geolocation services in networks that use narrow-band communication channels are discussed, as well as the relevant challenges faced by the TDoA approach. Then, we select five classic TDoA algorithms and evaluate their performance using simulation. Based on these results, we select the two providing the best accuracy (i.e., Chan's and Foy's). These algorithms were tested by the field measurements, using the specially designed low-cost gateways and test devices to estimate their real-life performance.


Chemical Modulation of Protein O-GlcNAcylation via OGT Inhibition Promotes Human Neural Cell Differentiation.
The enzymes that determine protein O-GlcNAcylation, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), act on key transcriptional and epigenetic regulators, and both are abundantly expressed in the brain. However, little is known about how alterations in O-GlcNAc cycling affect human embryonic stem cell (hESC) neural differentiation. Here, we studied the effects of perturbing O-GlcNAcylation during neural induction of hESCs using the metabolic inhibitor of OGT, peracetylated 5-thio-N-acetylglucosamine (Ac4-5SGlcNAc). Treatment of hESCs with Ac4-5SGlcNAc during induction limited protein O-GlcNAcylation and also caused a dramatic decrease in global levels of UDP-GlcNAc. Concomitantly, a subpopulation of neural progenitor cells (NPCs) acquired an immature neuronal morphology and expressed early neuronal markers such as β-III tubulin (TUJ1) and microtubule associated protein 2 (MAP2), phenotypes that took longer to manifest in the absence of OGT inhibition. These data suggest that chemical inhibition of OGT and perturbation of protein O-GlcNAcylation accelerate the differentiation of hESCs along the neuronal lineage, thus providing further insight into the dynamic molecular mechanisms involved in neuronal development.


Theatre personnel's perception of operating room resource allocation.
Operating rooms (OR) in hospitals represent big investments and must be utilized efficiently. Inaccurate scheduling of OR resources often results in delays of surgery or cancellations of procedures. These are costly to the patient, surgical team and hospital. Existing literatures in the OR management lack consensus on the method of evaluating management decisions from the perspectives of personnel or those affected by management decision-making processes. Eight key informant interviews were conducted. Also, 50 Operating Theatre Personnel (OTP), i.e., Surgeons, OR Nurses, Anaesthetists, and Executive Officers in the Nigeria's premier University Teaching Hospital were asked to complete a survey questionnaire concerning operating theatre resource allocation in the hospital. Five close-ended and 10 open-ended questions were used. (For example, how are the decisions to allocate OR resources in this hospital made?) Thematic analysis and descriptive statistics were done. The theoretical framework, accountability for reasonableness was applied. Forty-eight percent of the participants were ignorant of the framework guiding OR resource allocation. 54% of the respondents admitted the current mechanism for publicizing management decisions on OR resource allocation is ineffective. Another 50% of the respondents knew little about the mode of appealing against unfavourable allocation decisions. Participants' open ended responses revealed that hospital executives and a few consultant surgeons control the allocation of OR resources, with little recourse to OR personnel's concerns. If operating theatre stake holders are excluded in the planning, allocation and evaluation of OR resources, the efficiency required in surgical services would never be realized irrespective of the dexterity of the surgical team.


Expanding access to treatment for hepatitis C in resource-limited settings: lessons from HIV/AIDS.
The need to improve access to care and treatment for chronic hepatitis C virus (HCV) infection in resource-limited settings is receiving increasing attention. Key priorities for scaling up HCV treatment and care include reducing the cost of current and future treatment; simplifying the package of care; identifying opportunities to shift specific tasks to nonspecialists to overcome human resource constraints; service integration with human immunodeficiency virus (HIV) clinics, prison health services, and needle syringe and oral substitution therapy programs; improving surveillance, monitoring, and research; encouraging patient and community engagement; focusing specifically on the needs of vulnerable groups; and increasing financial and political commitment. Many of these obstacles have been addressed in rolling out treatment for human immunodeficiency virus during the last decade, and a number of lessons can be drawn to help improve access to HCV care.


Age-associated impact on presentation and outcome for penetrating thoracic trauma in the adult and pediatric patient populations.
Studies reporting on penetrating thoracic trauma in the pediatric population have been limited by small numbers and implied differences with the adult population. Our objectives were to report on a large cohort of pediatric patients presenting with penetrating thoracic trauma and to determine age-related impacts on management and outcome through comparison with an adult cohort. A Level I trauma center registry was queried between 2006 and 2012. All patients presenting with penetrating thoracic trauma were identified. Patient demographics, injury mechanism, injury severity, admission physiology, and outcome were recorded. Patients were compared, and outcomes were analyzed based on age at presentation, with patients 17 years or younger defining our pediatric cohort. A total of 1,423 patients with penetrating thoracic trauma were admitted during the study period. Two hundred twenty patients (15.5%) were pediatric, with 205 being adolescents (13-17 years) and 15 being children (≤ 12 years). In terms of management for the pediatric population, tube thoracostomy alone was needed in 32.7% (72 of 220), whereas operative thoracic exploration was performed in 20.0% (44 of 220). Overall mortality was 13.6% (30 of 220). There was no significant difference between the pediatric and adult population with regard to injury mechanism or severity, need for therapeutic intervention, operative approach, use of emergency department thoracotomy, or outcome. Stepwise logistic regression failed to identify age as a predictor for the need for either therapeutic intervention or mortality between the two age groups as a whole. However, subgroup analysis revealed that being 12 years or younger (odds ratio, 3.84; 95% confidence interval, 1.29-11.4) was an independent predictor of mortality. Management of traumatic penetrating thoracic injuries in terms of the need for therapeutic intervention and operative approach was similar between the adult and pediatric populations. Mortality from penetrating thoracic trauma can be predicted based on injury severity, the use of emergency department thoracotomy, and admission physiology for adolescents and adults. Children may be at increased risk for poor outcome independent of injury severity. Epidemiologic study, level III.


Report of an infant with noma (cancrum oris).
Noma (cancrum oris) is an infectious disease that destroys the oro-facial tissues and other neighboring structures in its fulminating course. The starting point of the disease is acute ulcero-necrotic gingivitis, which results in an extensive gangrenous plaque destroying all of the soft tissues of the face. It predominantly affects children aged 2-16 years and is primarily seen in areas where the socioeconomic standards are low and there is poor hygiene, as in developing countries. We discuss possible predisposing factors in cancrum oris such as malnutrition, infectious diseases, HIV infection, and immune compromise conditions. Poverty is the most important risk factor. We report the case of a 6-month-old child with noma and review the characteristic features of this disease.


Ionic mechanisms of the cardiac pacemaker potential.
The experimental evidence so far described in the literature is reviewed to explain the ionic mechanisms underlying the cardiac pacemaker potential in the sinoatrial node cell. Following gating mechanisms underlie the slow diastolic depolarization of the SA node cells. The delayed rectifier K+ channels (mainly the rapidly activated component of the delayed rectifier K+ currents, which is blocked by E-4031) activated during the preceding action potential are deactivated during diastole. The inactivation of the L-type Ca2+ channel is removed during the early diastolic period and results in an increasing inward current, provided that the amplitude of the window component is of significant amplitude. Because of its sustained nature, the removal of inactivation of the sustained inward current Ist, also generates inward current. The negative membrane potential near the maximum diastolic potential activates the hyperpolarization-activated non-selective cation current, I(f). Finally, the L-type Ca2+ channel is activated at the late phase of diastole depolarization, resulting in the maximum rate of rise of the action potential. These time- and voltage-dependent changes in membrane conductance occur in the presence of a significant background conductance. During the slow diastolic depolarization, Ist and IK may be the major component in the inward and outward currents, respectively.


Perioperative Management of Antithrombotic Medications: An Investigation into Current U. S. Ophthalmologic Recommendations.
To investigate the availability and content of educational statements or recommendations disseminated by U. S. ophthalmologic organizations regarding perioperative management of antithrombotic agents for ophthalmic and orbital surgery, given the highly variable management of these agents by U. S. ophthalmologists and limited consensus recommendations in the literature. National U. S. ophthalmic surgical organization websites were systematically examined for educational statements, which were reviewed for discussion of perioperative management of antithrombotic agents including antiplatelet and anticoagulant medications. A "statement" was defined as either: (a) a guideline directed toward ophthalmologists or (b) a surgical/clinical educational posting directed toward ophthalmologists or patients. Fourteen surgical organizations were identified, with eight of these publishing clinical/surgical educational statements. A total of 3408 organizational statements were identified, with 252 (7.4%) and 3156 (92.6%) statements directed toward physicians and patients, respectively. In total, 0.3% (9/3408) of statements discussed perioperative management of antithrombotics. These accounted for 0.8% (2/252) of ophthalmologist-directed statements and 0.2% (7/3156) of patient-directed statements. The majority of patient-directed statements (57.1%, 4/7) recommended that patients discuss antithrombotic cessation with their ophthalmologists, though ophthalmologist-directed information regarding these medications was scant or absent. Educational material from U. S. ophthalmologic organizations regarding perioperative management of antithrombotics is notably lacking despite the fact that ophthalmic and orbital surgeries carry unique vision-threatening hemorrhagic risks. Given these risks, as well as the medicolegal consequences of hemorrhagic complications in ophthalmic surgery, increased dissemination of educational material, and consensus statements by ophthalmic surgical organizations on the perioperative management of antithrombotics may be justified.


Survivorship in gynecologic cancer: enduring the treatment toward a new normal.
Women are living longer after a cancer diagnosis because of advances in early detection and treatment. However, although our ability to effectively treat gynecologic malignancies has improved, survivors of gynecologic cancer often face profound physical, emotional, sexual, and psychosocial challenges as a result of their cancer diagnosis and treatment. In this article, we discuss how patient comorbidities (i.e., obesity) and cancer treatment effects may adversely affect sexual health outcomes, gastrointestinal function, and general health among survivors of gynecologic cancer. The importance of a multidisciplinary, patient-centered approach to survivorship care is emphasized.


Lipoxygenase Activity Accelerates Programmed Spore Germination in Aspergillus fumigatus.
The opportunistic human pathogen Aspergillus fumigatus initiates invasive growth through a programmed germination process that progresses from dormant spore to swollen spore (SS) to germling (GL) and ultimately invasive hyphal growth. We find a lipoxygenase with considerable homology to human Alox5 and Alox15, LoxB, that impacts the transitions of programmed spore germination. Overexpression of loxB (OE::loxB) increases germination with rapid advance to the GL stage. However, deletion of loxB (ΔloxB) or its signal peptide only delays progression to the SS stage in the presence of arachidonic acid (AA); no delay is observed in minimal media. This delay is remediated by the addition of the oxygenated AA oxylipin 5-hydroxyeicosatetraenoic acid (5-HETE) that is a product of human Alox5. We propose that A. fumigatus acquisition of LoxB (found in few fungi) enhances germination rates in polyunsaturated fatty acid-rich environments.


[Community health services--more stressing for female than male physicians?].
A questionnaire was sent to all general practitioners at municipal health centres in Oslo in 1987. 74% of the doctors participated in the study, 38 women and 41 men. The results show that the major source of stress at work was high work load. The results also point to important gender differences. Compared with their male colleagues, the female general practitioners experienced higher job strain. They also found less opportunity to influence their working conditions. Female doctors more often experienced psychosomatic disorders and periods of sick leave. The results are discussed in relation to differences in patient selection, role strain and coping style.


The effect of the menstrual cycle on the sense of touch, grip strength and manual dexterity of dental students.
Objectives. This study aimed to evaluate through comparative tests the effect of the menstrual cycle on levels of depression, sleep quality and grip strength, fingertip touch and manual dexterity of students in the Dental Faculty. Methods. The study sample was formed from female students of the Dental Faculty. The total 70 participants comprised 31 from the first year and 39 from the final year. Evaluations were made in two different consecutive phases of the menstrual cycle. Data were collected using the Beck depression inventory (BDI), the Pittsburgh sleep quality index (PSQI), handgrip and lateral grip strength measurements, fingertip two-point discrimination sensory measurement, the Semmes-Weinstein monofilament test, the O'Connor tweezers skill test and the Purdue pegboard test. Results. A statistically significant difference was determined between the menstrual and ovulation phase measurements of the BDI, PSQI, Semmes-Weinstein monofilament test (right), the O'Connor tweezers skill test and Purdue pegboard test (right + left), and the Purdue Pegboard test (total and assembly) (p < 0.05). Conclusions. The menstrual cycle does not affect the sense of touch, grip strength and simple hand skills. However, task-focused skills requiring care and the manual dexterity needed for the use of instruments are affected.


Impact of active antibody-mediated rejection treatment on donor-specific antibodies in pediatric kidney transplant recipients.
AMR is a major cause of graft loss after kidney transplantation. We evaluated a retrospective cohort of 13 pediatric kidney transplant patients diagnosed with active AMR. All 13 patients were treated with plasmapheresis (PP), IVIg, and rituximab. Anti-HLA DSAs were measured at the time of transplantation, AMR diagnosis, 30 days post-rejection treatment, 90 days post-rejection treatment, and 24 ± 12 months post-AMR. A total of 68 DSAs were identified from 13 patients at the time of active AMR diagnosis. The primary objective of this study was to differentiate treatment response rates between class I and class II anti-HLA DSA post-AMR treatment. Overall, DSAs were significantly reduced at 30 days, and the reduction was sustained at 90 days post-treatment, even for class II anti-HLA and strongly positive DSAs. A significant difference between class I and class II anti-HLA DSA was observed at 30 days; however, between class significance was lost at 90-day follow-up due to continued class II anti-HLA DSA treatment response. Low DSA strength was predictive of treatment response. eGFR demonstrated significant improvement 90 days after AMR diagnosis compared to the initial value at the time of AMR, and the effect was sustained for 12 months. These results suggest that the AMR treatment is effective in pediatric kidney transplant recipients with an early diagnosis of active AMR across both class I and class II anti-HLA DSAs.


Osteocalcin activates lipophagy via the ADPN-AMPK/PPARα-mTOR signaling pathway in chicken embryonic hepatocyte.
Fatty liver hemorrhage syndrome (FLHS) is the leading cause of noninfectious mortality in caged layers worldwide. Osteocalcin (OCN) is a protein secreted by osteoblasts, and its undercarboxylated form (ucOCN) acts as a multifunctional hormone that protects laying hens from FLHS. Lipophagy is a form of selective autophagy that breaks down lipid droplets (LDs) through lysosomes, and defective lipophagy is associated with FLHS. The aim of this study was to investigate the effects of ucOCN on the lipophagy of chicken embryonic hepatocytes and associated the function of the adiponectin (ADPN) signaling pathway. In this study, chicken embryonic hepatocytes were divided into 5 groups: control (CONT), fat emulsion (FE, 10% FE, v/v), FE with ucOCN at 1 ng/mL (FE-LOCN), 3 ng/mL (FE-MOCN), and 9 ng/mL (FE-HOCN). In addition, 4 μM AdipoRon, an adiponectin receptor agonist, was used to investigate the function of ADPN. The results showed that compared with CONT group, FE promoted the levels of phosphorylation of mammalian target of rapamycin (p-mTOR) (P < 0.05) and decreased the mRNA expression of ADNP receptors (AdipoR1 and AdipoR2). Compared with FE group, 3 and 9 ng/mL ucOCN inhibited the levels of autophagy adaptor p62 and p-mTOR (P < 0.05), increased the ratios of LC3-II/LC3-I (P < 0.05) and phosphorylated adenosine 5'-monophosphate-activated protein kinase (p-AMPK)/AMPK (P < 0.05), as well as the levels of peroxisome proliferator-activated receptor α (PPAR-α) and ADPN (P < 0.05). In addition, ucOCN at the tested concentrations increased the colocalization of LC3 and LDs in fatty hepatocytes. Administrated 4 μM AdipoRon activated AdipoR1 and AidpoR2 mRNA expression (P < 0.05), decreased the concentrations of triglyceride (P < 0.05), without effects on cell viability (P > 0.05). AdipoRon also increased the LC3-II/LC3-I ratio (P < 0.05) and the levels of p-AMPK/AMPK and PPAR-α (P < 0.05). In conclusion, the results reveal that ucOCN regulates lipid metabolism by activating lipophagy via the ADPN-AMPK/PPARα-mTOR signaling pathway in chicken embryonic hepatocytes. The results may provide new insights for controlling FLHS in laying hens.


[Biosynthesis and metabolism of prostaglandins in the small intestine of rats exposed to cholera enterotoxin].
The effect of cholera enterotoxin on biosynthesis and metabolism of prostaglandins in the rat small intestine was studied. It was shown that in the course of action of cholera enterotoxin maximal synthesis and metabolism of prostaglandins (PG) was observed within the first 30 minutes after enterotoxin administration into the isolated intestinal loop. It was found that cholera enterotoxin induced, on the one hand, the shift in the correlation of different types of prostaglandins synthetized in vitro and, on the other, differentially activated PG synthesis and metabolism after pretreatment with the PG-synthetase inhibitor indomethacin.


Relationship between lateral diffusion, collision frequency, and electron transfer of mitochondrial inner membrane oxidation-reduction components.
Fluorescence recovery after photobleaching was used to determine the diffusion coefficients of the oxidation-reduction (redox) components ubiquinone, complex III (cytochromes b-c1), cytochrome c, and complex IV (cytochrome oxidase) of the mitochondrial inner membrane. All redox components diffuse in two dimensions as common-pool electron carriers. Cytochrome c diffuses in two and three dimensions concomitantly, and its diffusion rate, unlike that of all other redox components, is modulated along with its activity by ionic strength. The diffusion coefficients established in this study reveal that the theoretical diffusion-controlled collision frequencies of all redox components are greater than their experimental maximum (uncoupled) turnover numbers. Since electron transport is slower than the theoretical limit set by the lateral diffusion of the redox components, ordered chains, assemblies, or aggregates of redox components are not necessary to account for electron transport. Rather, mitochondrial electron transport is diffusion coupled, consistent with a "random-collision model" for electron transport.


[Thermoregulatory parameters of normal and developmentally retarded newborn rat pups].
The millicalorimetry with simultaneous recording of the motor activity, temperature of the brown adipose tissue and rectal temperature revealed a dysfunction of the brown adipose tissue and motor activity as the sources of additional heat production in the drop of ambient temperature in underdeveloped newborn rats.


Crystal structure of Korean pine (Pinus koraiensis) 7S seed storage protein with copper ligands.
The prevalence of food allergy has increased in recent years, and Korean pine vicilin is a potential food allergen. We have previously reported the crystallization of Korean pine vicilin purified from raw pine nut. Here we report the isolation of vicilin mRNA and the crystal structure of Korean pine vicilin at 2.40 Å resolution. The overall structure of pine nut vicilin is similar to the structures of other 7S seed storage proteins and consists of an N-terminal domain and a C-terminal domain. Each assumes a cupin fold, and they are symmetrically related about a pseudodyad axis. Three vicilin molecules form a doughnut-shaped trimer through head-to-tail association. Structure characterization of Korean pine nut vicilin unexpectedly showed that, in its native trimeric state, the vicilin has three copper ligands. Sequence alignments suggested that the copper-coordinating residues were conserved in winter squash, sesame, tomato, and several tree nuts, while they were not conserved in a number of legumes, including peanut and soybean. Additional studies are needed to assess whether the copper-coordinating property of vicilins has a biological function in the relevant plants. The nutritional value of this copper-coordinating protein in tree nuts and other edible seeds may be worth further investigations.


An Integrated Metabolomic Study of Osteoporosis: Discovery and Quantification of Hyocholic Acids as Candidate Markers.
Osteoporosis is becoming a highly prevalent disease in a large proportion of the global aged population. Serum metabolite markers may be important for the treatment and early prevention of osteoporosis. Serum samples from 32 osteoporosis and 32 controls were analyzed by untargeted metabolomics and lipidomic approaches performed on an ultra-high performance liquid chromatography and high-resolution mass spectrometry (UHPLC-HRMS) system. To find systemic disturbance of osteoporosis, weighted gene correlation network analysis (WGCNA) and statistical methods were employed for data-mining. Then, an in-depth targeted method was utilized to determine potential markers from the family of key metabolites. As a result, 1,241 metabolites were identified from untargeted methods and WGCNA indicated that lipids metabolism is deregulated and glycerol phospholipids, sphingolipids, fatty acids, and bile acids (BA) are majorly affected. As key metabolites of lipids metabolism, 66 bile acids were scanned and 49 compounds were quantified by a targeted method. Interestingly, hyocholic acids (HCA) were found to play essential roles during the occurrence of osteoporosis and may be potential markers. These metabolites may be new therapeutic or diagnosis targets for the screening or treatment of osteoporosis. Quantified measurement of potential markers also enables the establishment of diagnostic models for the following translational research in the clinic.


Wnt5a regulates midbrain dopaminergic axon growth and guidance.
During development, precise temporal and spatial gradients are responsible for guiding axons to their appropriate targets. Within the developing ventral midbrain (VM) the cues that guide dopaminergic (DA) axons to their forebrain targets remain to be fully elucidated. Wnts are morphogens that have been identified as axon guidance molecules. Several Wnts are expressed in the VM where they regulate the birth of DA neurons. Here, we describe that a precise temporo-spatial expression of Wnt5a accompanies the development of nigrostriatal projections by VM DA neurons. In mice at E11.5, Wnt5a is expressed in the VM where it was found to promote DA neurite and axonal growth in VM primary cultures. By E14.5, when DA axons are approaching their striatal target, Wnt5a causes DA neurite retraction in primary cultures. Co-culture of VM explants with Wnt5a-overexpressing cell aggregates revealed that Wnt5a is capable of repelling DA neurites. Antagonism experiments revealed that the effects of Wnt5a are mediated by the Frizzled receptors and by the small GTPase, Rac1 (a component of the non-canonical Wnt planar cell polarity pathway). Moreover, the effects were specific as they could be blocked by Wnt5a antibody, sFRPs and RYK-Fc. The importance of Wnt5a in DA axon morphogenesis was further verified in Wnt5a-/- mice, where fasciculation of the medial forebrain bundle (MFB) as well as the density of DA neurites in the MFB and striatal terminals were disrupted. Thus, our results identify a novel role of Wnt5a in DA axon growth and guidance.


Involvement of AMPA receptor GluR2 subunits in stimulus-reward learning: evidence from glutamate receptor gria2 knock-out mice.
Presence of the glutamate receptor 2 (GluR2) subunit prevents calcium influx through AMPA-receptor complexes; deletion of this subunit results in enhanced hippocampal long-term potentiation. We investigated whether mice lacking the GluR2 subunit [gria2 knock-out (KO) mice] displayed impairments in learning stimulus-reward associations, and the subsequent ability of reward-paired cues to control motivated behavior. Both gria2 KO and wild-type (WT) mice learned to associate a light/tone stimulus with food delivery, as evidenced by approach toward the food magazine after the presentation of the cues (pavlovian conditioning). Subsequently, the cues also served to reinforce an operant response in both KO and WT mice (conditioned reinforcement), although response rates were greater in gria2 KOs. Responding for conditioned reinforcement was enhanced after 0.5 mg/kg amphetamine administration in WT mice, but not in KO mice. The ability of the cues to elicit approach behavior (conditioned approach) and to enhance responding for the reward (pavlovian-to-instrumental transfer; PIT) were also impaired in gria2 KO mice. This pattern of behavior resembles that seen after lesions of the central nucleus of the amygdala (CeA), an area rich in GluR2-containing AMPA receptors. Immunostaining revealed reduced GluR1 expression within both the basolateral amygdala and the CeA, suggesting that the behavioral deficits observed were unlikely to be caused by compensatory changes in GluR1. These results suggest that GluR2-containing AMPA receptors, possibly within the CeA, are critical for the formation of stimulus-reward associations necessary for PIT and conditioned approach, but are not involved in the plastic processes underlying the attribution of motivational value to the conditioned stimulus (CS).


Fatal right ventricular failure and pulmonary hypertension after protamine administration during cardiac transplantation.
Protamine sulfate is the only Food and Drug administration approved medication for reversal of intraoperative heparin-induced anticoagulation during cardiac and vascular surgeries. One of the rare side effects of protamine sulfate is an idiosyncratic reaction resulting in acute pulmonary hypertension (APH) and right ventricular (RV) failure occurring after protamine administration. These reactions are rare but catastrophic with high mortality. A 36-year-old female with severe congestive heart failure was undergoing cardiac transplant surgery. After successful implantation of the donor heart, the patient was weaned off cardiopulmonary bypass. Protamine was then administered to reverse the heparin anticoagulation. She immediately developed APH and RV failure immediately after protamine infusion. The patient required immediate administration of inotropic agents, nitric oxide (NO), and subsequently required a number of mechanical support devices including an RV assist device (RVAD) and ultimately full veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Despite heroic efforts, the patient developed refractory multi-organ failure in the Intensive Care Unit and died after family requested discontinuation of resuscitative efforts. This case probably represents the first reported occurrence of fatal protamine-induced APH and ventricular failure in the setting of cardiac transplantation surgery. A number of interventions including inhaled NO, systemic vasopressors, RVAD, and ultimately VA-ECMO failed to reverse the situation, and the patient died of multi-organ failure.


Clouds and rainbows on the HIPAA horizon.
In the planning phase for several years, the administrative simplification provisions of the Health Insurance Portability and Accountability Act of 1996 (HIPAA) finally appear ready for implementation. The Health Care Financing Administration (HCFA) expects that the major HIPAA measures will be released in late 1999. For group practices, it is expected that implementation of these provisions will be complicated and consume significant amounts of time and money. Still, the end result should justify the effort.


ERCC1/XPF protects short telomeres from homologous recombination in Arabidopsis thaliana.
Many repair and recombination proteins play essential roles in telomere function and chromosome stability, notwithstanding the role of telomeres in "hiding" chromosome ends from DNA repair and recombination. Among these are XPF and ERCC1, which form a structure-specific endonuclease known for its essential role in nucleotide excision repair and is the subject of considerable interest in studies of recombination. In contrast to observations in mammalian cells, we observe no enhancement of chromosomal instability in Arabidopsis plants mutated for either XPF (AtRAD1) or ERCC1 (AtERCC1) orthologs, which develop normally and show wild-type telomere length. However, in the absence of telomerase, mutation of either of these two genes induces a significantly earlier onset of chromosomal instability. This early appearance of telomere instability is not due to a general acceleration of telomeric repeat loss, but is associated with the presence of dicentric chromosome bridges and cytologically visible extrachromosomal DNA fragments in mitotic anaphase. Such extrachromosomal fragments are not observed in later-generation single-telomerase mutant plants presenting similar frequencies of anaphase bridges. Extensive FISH analyses show that these DNAs are broken chromosomes and correspond to two specific chromosome arms. Analysis of the Arabidopsis genome sequence identified two extensive blocks of degenerate telomeric repeats, which lie at the bases of these two arms. Our data thus indicate a protective role of ERCC1/XPF against 3' G-strand overhang invasion of interstitial telomeric repeats. The fact that the Atercc1 (and Atrad1) mutants dramatically potentiate levels of chromosome instability in Attert mutants, and the absence of such events in the presence of telomerase, have important implications for models of the roles of recombination at telomeres and is a striking illustration of the impact of genome structure on the outcomes of equivalent recombination processes in different organisms.


Medicare Advantage reforms: comparing House and Senate bills.
The Medicare Advantage (MA) program, which enables Medicare beneficiaries to enjoy private health plan coverage, is a major element of the current health care reform discussion on Capitol Hill--in large part because payments to MA plans in 2009 are expected to run at least $11 billion more than traditional Medicare would have cost. While the pending Senate and House bills both endeavor to reduce these extra MA payments, their approaches are different. The bills also differ on other aspects of reforming the MA program, such as plans' allowable geographic areas, their risk-adjustment systems and reporting requirements, their potential bonuses for achieving high-quality care and providing good management, and their beneficiary protections. This issue brief compares the above and other provisions in the House and Senate bills, which have a common overall goal to improve the value that Medicare obtains for the dollars it spends


Measurement errors resulted from misalignment errors of the retarder in a rotating-retarder complete Stokes polarimeter.
Rotatable retarder fixed polarizer (RRFP) Stokes polarimeters, which employ uniformly spaced angles over 180° or 360°, are most commonly used to detect the state of polarization (SOP) of an electromagnetic (EM) wave. The misalignment error of the retarder is one of the major error sources. We suppose that the misalignment errors of the retarder obey a uniform normal distribution and are independent of each other. Then, we derive analytically the covariance matrices of the measurement errors. Based on the covariance matrices derived, we can conclude that 1) the measurement errors are independent of the incident intensity s0, but seriously depend on the Stokes parameters (s1, s2, s3) and the retardance of the retarder δ; 2) for any mean incident SOP, the optimal initial angle and retardance to minimize the measurement error both can be achieved; 3) when N = 5, 10, 12, the initial orienting angle could be used as an added degree of freedom to strengthen the immunity of RRFP Stokes polarimeters to the misalignment error. Finally, a series of simulations are performed to verify these theoretical results.


Visible-Light-Driven Reductive Carboarylation of Styrenes with CO2 and Aryl Halides.
The first example of visible-light-driven reductive carboarylation of styrenes with CO2 and aryl halides in a regioselective manner has been achieved. A broad range of aryl iodides and bromides were compatible with this reaction. Moreover, pyridyl halides, alkyl halides, and even aryl chlorides were also viable with this method. These findings may stimulate the exploration of novel visible-light-driven Meerwein arylation-addition reactions with user-friendly aryl halides as the radical sources and the photocatalytic utilization of CO2.


Nitric oxide (no), citrulline - no cycle enzymes, glutamine synthetase and oxidative stress in anoxia (hypobaric hypoxia) and reperfusion in rat brain.
Nitric oxide is postulated to be involved in the pathophysiology of neurological disorders due to hypoxia/ anoxia in brain due to increased release of glutamate and activation of N-methyl-D-aspartate receptors. Reactive oxygen species have been implicated in pathophysiology of many neurological disorders and in brain function. To understand their role in anoxia (hypobaric hypoxia) and reperfusion (reoxygenation), the nitric oxide synthase, argininosuccinate synthetase, argininosuccinate lyase, glutamine synthetase and arginase activities along with the concentration of nitrate /nitrite, thiobarbituric acid reactive substances and total antioxidant status were estimated in cerebral cortex, cerebellum and brain stem of rats subjected to anoxia and reperfusion. The results of this study clearly demonstrated the increased production of nitric oxide by increased activity of nitric oxide synthase. The increased activities of argininosuccinate synthetase and argininosuccinate lyase suggest the increased and effective recycling of citrulline to arginine in anoxia, making nitric oxide production more effective and contributing to its toxic effects. The decreased activity of glutamine synthetase may favor the prolonged availability of glutamic acid causing excitotoxicity leading to neuronal damage in anoxia. The increased formation of thiobarbituric acid reactive substances and decreased total antioxidant status indicate the presence of oxidative stress in anoxia and reperfusion. The increased arginase and sustained decrease of GS activity in reperfusion group likely to be protective.


Effect of smoking reduction and cessation on the plasma levels of the oxidative stress biomarker glutathione--Post-hoc analysis of data from a smoking cessation trial.
Cigarette smoke contains high concentrations of free radical components that induce oxidative stress. Smoking-induced oxidative stress is thought to contribute to chronic obstructive pulmonary disease, cardiovascular disease and lung cancer through degenerative processes in the lung and other tissues. It is uncertain however whether smoking cessation lowers the burden of oxidative stress. We used data from a randomized controlled cessation trial of 434 current smokers for a post-hoc examination of the effects of smoking cessation on blood plasma levels of total glutathione (tGSH), the most abundant endogenous antioxidant in cells, and total cysteine (tCys), an amino acid and constituent of glutathione. Smoking status was validated based on serum cotinine levels. Multivariate linear mixed models were fitted to examine the association of smoking cessation and change in cigarette consumption with tGSH and tCys. After 12 months follow-up, quitters (n=55) had significantly increased levels of tGSH compared to subjects who continued to smoke (P<0.01). No significant change in tGSH was found for subjects who continued to smoke but reduced their intensity of smoking. No significant effect of smoking cessation or reduction was observed on levels of tCys. These results suggest that smoking cessation but not smoking reduction reduces levels of oxidative stress.


Approach to procedures in neonates.
Physical constraints and metabolic differences in neonates require that special attention is given to performing procedures in this patient group. Neonates have a thinner dermis and a greater surface-to-weight ratio, allowing for easier invasion through the skin barrier. The enzymes for metabolism of agents and defense against organisms inside the body are not fully developed in infants. Very premature neonates also have less circulating albumin, making the effective concentration of circulating agent even greater. The infant is prone to unanticipated movement during procedures, such as rolling on the procedure table. The neonatal period is the most common time period for malformations to become manifest on the skin, and invasion of some of these lesions can produce morbidity. These and other factors affect the choice of the type of procedure used, the timing for intervention, and the approach to intervention in this age group. This article reviews the important considerations for approaching procedures and offers suggestions for safe and effective methods of reliably producing the intended outcome.


Evaluation of Standard E TB-Feron Enzyme-Linked Immunosorbent Assay for Diagnosis of Latent Tuberculosis Infection in Health Care Workers.
The laboratory diagnosis of latent tuberculosis infection (LTBI) is mainly performed with interferon gamma release assays (IGRAs). We compared the performance of a new enzyme-linked immunosorbent assay (ELISA)-based IGRA, the Standard E TB-Feron ELISA (TBF; SD Biosensor, Gyeonggi-do, Republic of Korea), with that of a widely used assay, the QuantiFERON-TB Gold In-Tube assay (QFT-GIT; Qiagen, Hilden, Germany), in a population of 425 health care workers (HCWs). All HCWs were screened by both assays per the manufacturers' protocols and in a cross-manner, where tube sets from one assay were used with the alternative ELISA. The results were compared both qualitatively and quantitatively. TBF and QFT-GIT identified 11.3% (48/425) and 12.9% (55/425) of the positive samples, respectively. TBF demonstrated 81.6% positive and 97.4% negative percent agreement with QFT-GIT, with a Cohen's kappa value of 0.78 (strong agreement). Discordant results were detected in 20 subjects (4.3%): 13 samples (65.0%) were TBF negative and QFT-GIT positive, 6 samples (30.0%) were TBF positive and QFT-GIT negative, and 1 sample provided TBF and QFT-GIT indeterminate/negative results. We observed a statistically significant degree of correlation between the interferon gamma reactivity between the two assays (Spearman's rho [rs ] value = 0.551, P < 0.01) and between standard assays and cross-manner tests (rs value range, 0.449 to 0.816; P < 0.01 for all combinations). Cross-manner tests also revealed that the ELISA kit of TBF provided higher values for the tube containing the tuberculosis (TB) antigen and the negative-control tube than the ELISA of QFT-GIT under the same conditions (P < 0.01), although these differences disappeared when the value for the negative-control tube was subtracted from that for the TB antigen tube. TBF showed a comparable and acceptable clinical performance in detecting LTBI compared to QFT-GIT. TBF represents a useful alternative tool as an ELISA-based IGRA, especially for large-scale screening for LTBI in HCWs.


Stretch-activated potassium channels in renal proximal tubule.
A short open-time potassium (K) channel that has previously been identified in the basolateral membrane of Necturus proximal tubule (17) is activated by membrane stretch. Application of between 12 and 20 cmH2O negative pressure to the patch pipette reversibly increases mean number of open basolateral K channels (NP0) by a factor of 5.3 +/- 2 in cell-attached patches (n = 4) and a factor of 13.7 +/- 5 in excised patches (n = 8). This stretch activation does not alter channel selectivity or conductance and depends on neither the direction of K current nor the orientation of the patch ("inside-out" vs. "outside-out"). The increase in NP0 occurs within seconds after applying negative pressure to the patch and is proportional to applied negative pressure. Stretch activation of the basolateral potassium channel may play an important role in proximal tubule cell volume regulation. For example, if swelling stretches the basolateral membrane, the resulting increase in NP0 could restore cell volume by loss of K (with an accompanying anion) followed by osmotic exit of water.


Attitudes and practices of complementary and alternative medicine among patients attending primary care center in Saudi Arabia: A prospective cross-sectional study.
Estimated complementary and alternative medicine (CAM) usage in Saudi Arabia is 70%. The Saudi Food and Drug Authority, National Center for Complementary and Alternative Medicine (NCCAM) regulates the license-based practices of various CAM modalities including procedures, herbs, and devices. As an aid to help primary care physicians for understanding CAM practices among general population, this study aimed to explore the prevalence of CAM along with its most common modality, and to understand attitude and practices among patients attending primary care center in Riyadh (Saudi Arabia). A prospective cross-sectional study was conducted among 403 literate patients aged more than 18 years, coming to the primary care center for regular check-up from 1st April 2019 to 1st April 2020 Saudi Arabia. Data was collected using self-administered questionnaire. Around 44.5% participants had practiced one method of alternative medicine in their life. Majority of participants who attended primary care centers belonged to the age group of 18-39 years (71.1%). The most common used method of alternative medicine was honey healing. More than half of the study participants had heard about the CAM from their family and friends. Nearly 45.7% had stated that the CAM cannot be used without consulting a medical professional. Nearly 3/4th population used it for treating up to 3 ailments. Use of alternative medicine was found to be prevalent in Riyadh. Family and friends were recognized as gatekeepers for propagating information about CAM usage in the society. Primary healthcare physicians need to be trained on prevalent practices of CAM to understand the societal needs.


Fetal Anatomic Imaging Between 11 and 14 Weeks Gestation.
Fetal imaging between 11 and 14 weeks is a standard component of prenatal risk assessment for aneuploidy. Evaluating the fetus during this gestational age window provides the opportunity to reliably examine anatomic structures. Using a defined imaging protocol, approximately 50% of major abnormalities can be detected. Some abnormalities should almost always be detected, some may be detected on occasion and others are not currently detectable. Imagers must be familiar with embryologic patterns of development and natural history of anomalies. Patients must be informed of the limitations of early anatomic evaluation. Currently, early anatomic evaluation does not replace the standard second trimester evaluation.


The role of the pharmacist in mental health: An investigation of the impact of pharmacist-led interventions on psychotropic medication adherence in patients with diabetes.
To evaluate the impact of targeted telepharmacist mental health adherence interventions for patients with type 2 diabetes. This retrospective review involved the analysis of a telepharmacist-led mental health intervention. The subjects included: patients aged 18 years or more with type 2 diabetes, enrolled in an adherence service and who had been prescribed psychotropics. Psychotropic medication adherence was measured using the proportion of days covered (PDC) 6 months before and after the telepharmacist-led medication intervention. A total of 8167 patients (67% women), with a mean age of 63 ± 11 years, were included in the study. Most alerts for psychotropics were for selective serotonin reuptake inhibitors (SSRIs) (53%, n = 4334), selective norepinephrine reuptake inhibitors (SNRIs) (22%, n = 1775), second-generation antipsychotics (11%, n = 909), and bupropion (10%, n = 782). Alerts with the greatest volume of PDCs (above 85%) at postintervention follow up included SSRIs (51%, n = 2228), SNRIs (50%, n = 884), and second-generation antipsychotics (47%, n = 424). Before the alert, the mean PDC was 66% ± 12% across all medications studied. Post intervention, the mean PDC rose to 79% ± 19. A paired t-test revealed statistically significant improvement in adherence overall, with the greatest change observed in these alert groups: SSRIs (P < 0.001), alpha-2 antagonist (P < 0.001), SNRIs (P < 0.001), and bupropion (P < 0.001). This retrospective review showed that pharmacist-led targeted, adherence interventions greatly improved psychotropic medication adherence in adult patients with type 2 diabetes. Future work is warranted to investigate the impact on type 2 diabetes medication adherence and health markers (e.g., HbA1c values) in larger and more diverse populations of patients with comorbid type 2 diabetes and a mental health condition.


[Micropapillary component in lung adenocarcinoma generated in emphysema].
We report a case of 72-year-old male of adenocarcinoma with micropapillary component of the lung. Though the hilar lymph node metastasis was eminent, primary site was difficult to identify by using computed tomography (CT). SUV max with positron emission (PET)-CT in the case suggested the lung cancer in the emphysematous lung and it became an operation. The pathology diagnosis of the excision lungs was T4 (pml) N1 (#10, 12u) M0 stage IIIB. It was generated in emphysema, and it seemed that an adenocarcinoma with micropapillary component that did typical progress.


Enrichment of canalicular membrane with cholesterol and sphingomyelin prevents bile salt-induced hepatic damage.
These studies were undertaken to characterize the role of plasma membrane cholesterol in canalicular secretory functions and hepatocyte integrity against intravenous taurocholate administration. Cholesterol and sphingomyelin concentrations and cholesterol/phospholipid ratios were significantly increased in canalicular membranes of diosgenin-fed rats, suggesting a more resistant structure against solubilization by taurocholate. During taurocholate infusion, control rats had significantly decreased bile flow, whereas diosgenin-fed animals maintained bile flow. Maximal cholesterol output increased by 176% in diosgenin-fed rats, suggesting an increased precursor pool of biliary cholesterol in these animals. Maximal phospholipid output only increased by 43% in diosgenin-fed rats, whereas bile salt output remained at control levels. The kinetics of glutamic oxalacetic transaminase, lactic dehydrogenase, and alkaline phosphatase activities in bile showed a significantly faster release in control than in diosgenin-fed rats. After 30 min of intravenous taurocholate infusion, necrotic hepatocytes were significantly increased in control animals. Preservation of bile secretory functions and hepatocellular cytoprotection by diosgenin against the intravenous infusion of toxic doses of taurocholate was associated with an increased concentration of cholesterol and sphingomyelin in the canalicular membrane. The increase of biliary cholesterol output induced by diosgenin was correlated to the enhanced concentration of cholesterol in the canalicular membrane.


Guillain-Barré syndrome following H1N1 immunization in a pediatric patient.
To report a case of Guillain-Barré syndrome (GBS) following a dose of influenza A (H1N1) vaccine (Arepanrix). An 11-year-old boy was admitted to the hospital after presenting with facial diplegia; abdominal, forehead, and thigh pain; and acute cervical pain. He had received the Arepanrix H1N1 subcutaneous vaccine 13 days before symptom onset. The neurologic examination also revealed a symmetric bilateral paralysis of the VIIth cranial nerve and intense pain, proximal weakness of the shoulder girdles and pelvis, and preserved deep tendon reflexes. Cerebrospinal fluid analysis revealed an albuminocytologic dissociation. Therefore, a diagnosis of atypical GBS following vaccination against HINI influenza was made. Based on the clinical evaluation, laboratory test results, neurologic features, and the exclusion of alternative diagnoses, the Naranjo probability scale revealed a probable relationship between the clinical manifestations of GBS and the vaccine against influenza A (H1N1) received by the patient. This is the first published case for the 2009 influenza pandemic in children. While recent studies have found inconclusive results on the association between influenza vaccine and GBS, all suspected cases should be published for further evaluation.


How do urodynamics findings influence the treatment of the typical patient with overactive bladder?
Overactive bladder (OAB) is a clinical symptom complex whose hallmark is the symptom of urinary urgency, usually accompanied by frequency and nocturia, with or without urgency incontinence. Historically, urodynamics (UDS) evaluation has not been recommended in the initial evaluation of OAB, since it is defined primarily by clinical symptoms. As the pathophysiology of the OAB complex has become more clearly elucidated from recent studies, the role of UDS has again become a topic of discussion as a tool that can provide objective data to reflect these new findings. The utility of UDS in the diagnosis and treatment of OAB is still evolving, but in certain clinical scenarios, especially when empiric treatment has failed, it can provide definitive information that can identify associated pathologies and/or alter the treatment course. Herein, we will discuss the current literature regarding use of UDS in OAB patients and offer our own opinions as to its use.


Emotion detection from EEG using transfer learning.
In this study, we employed transfer learning to overcome the challenge of limited data availability in EEG-based emotion detection. The base model used in this study was Resnet50. Additionally, we employed a novel feature combination in EEG-based emotion detection. The input to the model was in the form of an image matrix, which comprised Mean Phase Coherence (MPC) and Magnitude Squared Coherence (MSC) in the upper-triangular and lower-triangular matrices, respectively. We further improved the technique by incorporating features obtained from the Differential Entropy (DE) into the diagonal. The dataset used in this study, SEED EEG (62 channel EEG), comprises three classes (Positive, Neutral, and Negative). We calculated both subject-independent and subject-dependent accuracy. The subject-dependent accuracy was obtained using a 10-fold cross-validation method and was 93.1%, while the subject-independent classification was performed by employing the leave-one-subject-out (LOSO) strategy. The accuracy obtained in subject-independent classification was 71.6%. Both of these accuracies are at least twice better than the chance accuracy of classifying 3 classes. The study found the use of MSC and MPC in EEG-based emotion detection promising for emotion classification. The future scope of this work includes the use of data augmentation techniques, enhanced classifiers, and better features for emotion classification.


A radiological review of cervical spine injuries from an accident and emergency department: has the ATLS made a difference?
The importance of visualizing the entire cervical spine on radiological examination in patients with cervical trauma is well known. A review of the cervical films of 98 patients attending an accident and emergency (A&E) department was undertaken in order to assess the adequacy of imaging. It was found that 33.7% of the films were not sufficient to exclude fracture or dislocation of the cervical spine. The number of patients with inadequate views was significantly reduced when an advanced trauma life support trained senior doctor was involved.


Parkinson's Disease and Its Dermatological Associations: Is Your Skin Whispering You a Diagnosis?
Parkinson's disease (PD) is a neurodegenerative disease characterized clinically by the triad of resting tremor, rigidity, and bradykinesia. Although PD is primarily known for motor disturbance, 98.6% of patients experience one or more non-motor symptoms at all stages of the disease. Dermatological disorders are discussed as common non-motor associations of PD since the 20th century. Many studies have shown that patients of PD are predisposed to skin disorders. This article is a traditional review done to analyze the association between PD and its dermatological manifestations. We did a literature search using six keywords in the PubMed database and took the relevant articles published in the last 10 years. We reviewed more than 100 articles, which also included animal studies. On meticulous review, we observed an increased incidence of certain skin disorders like seborrheic dermatitis, bullous pemphigoid, rosacea, and melanoma in patients of PD. These disorders share either common risk factors or underlying mechanisms revolving around genetics, immunology, inflammation, and pathophysiology of PD, but the exact causation yet seems obscured. We believe that this opens a horizon for more research in the link between the skin and nervous system. We also emphasize that the dermatologists, neurologists and general physicians should address the cutaneous disorders in PD timely, educate their patients, help them lessen the psychosocial distress, and improve their quality of life.


Miltefosine suppresses inflammation in a mouse model of inflammatory bowel disease.
The repertoire of immunomodulators that can be used for the treatment of inflammatory bowel disease is limited. The use of these drugs is further restricted by the occurrence of side effects in a proportion of patients. Miltefosine (hexadecylphosphocholine) is a lipid drug developed in the 1980s for the treatment of cancer but is nowadays best known for its application in the oral treatment of leishmaniasis. Although the exact mechanism of action of miltefosine has yet to be elucidated, the drug has previously been shown to inhibit phospholipases and protein kinase C, both key components of proproliferative signal transduction in T cells. Stimulated peripheral blood lymphocyte were treated with miltefosine, and proliferation was measured. We use the CD45RB T-cell transfer colitis model to investigate the effect of miltefosine treatment on intestinal inflammation. Effects on the severity of colitis were studied by histochemical and immunohistochemical staining, and cytokine levels were determined using a cytokine bead array. Miltefosine inhibited T-cell proliferation in vitro. In the transfer model, miltefosine significantly ameliorated the severity of colitis as measured by clinical, (immuno)histochemical, and biochemical parameters. Miltefosine inhibits T-cell proliferation and effectively reduces inflammation in the T-cell transfer model. The drug may therefore be a candidate immunomodulator for inflammatory bowel disease.


[Immunoreactive disorders and their correction in patients with rhegmatogenous retinal detachment complicated by vitreoretinal proliferation].
Examination of the immunologic state of 73 patients with rhegmatogenous retinal detachment complicated by vitreoretinal proliferation has revealed correlation between the severity of the latter and disturbances in the immune state of the patient's body. 44% of patients with the stage C and 62% of patients with the stage D have immunodeficiency expressed by reduced level of T- and B-lymphocytes and their subpopulation. It is shown that disturbances in immunoreactivity can serve as an unfavourable sign for prognosis of effectiveness of surgical intervention in patients with rhegmatogenous retinal detachment. In 70% of the patients these disturbances lead to unfavourable outcome of the operation. For normalization of the revealed disturbances in the immune state, immunomodulator thymaline was used in a complex treatment of 17 patients. The preparation rose the effectiveness of the treatment in 78% of patients and reduced the number of postoperative complications. It is recommended to study the immunologic state of the patient with rhegmatogenous retinal detachment complicated by vitreoretinal proliferation for the purpose of its further correction and a higher effectiveness of surgical treatment of such patients.


Concurrence of limb girdle muscular dystrophy and myasthenia gravis.
We describe a case of limb girdle muscular dystrophy with associated myasthenia gravis. This association has not been previously noted in the literature. The unusual feature of the case was that symptoms coexisted for several years before a correct diagnosis was made. The diagnosis was based on the clinical picture and the results of the muscle biopsy and electrophysiologic testing. This case serves to illustrate the fact that a separate problem should be considered when the clinical picture is not compatible with the underlying diagnosis.


Evaluation of effect of charge and lipid coating on ability of 60-nm nanoparticles to cross an in vitro model of the blood-brain barrier.
A cell culture model of the blood-brain barrier (BBB) consisting of a coculture of bovine brain capillary endothelial cells and rat astrocytes has been used to examine the ability of 60-nm nanoparticles with different physicochemical characteristics to cross the BBB. Neutral, anionic, and cationic nanoparticles were made from crosslinked malto-dextrins derivatized or not (neutral) with phosphates (anionic), quaternary ammoniums (cationic) ligands. Then, these particles were coated or not with a lipid bilayer made of dipalmitoyl phosphatidyl choline and cholesterol. Lipid coating of ionically charged nanoparticles was able to increase BBB crossing 3- or 4-fold compared with uncoated particles, whereas coating of neutral particles did not significantly alter their permeation characteristics across the endothelial cell monolayer. Lipid-coated nanoparticles were nontoxic toward BBB integrity, and crossed the BBB by transcytosis without any degradation. Furthermore, a 27-fold increase in albumin transport was observed when albumin had previously been loaded in the cationic lipid-coated nanoparticles. The influence of red blood cells was studied; a marked inhibition of the transport was observed, probably due to strong interaction between nanoparticles and red blood cells.


Rare hereditary diseases with defects in DNA-repair.
The human genome is constantly exposed to various sources of DNA damage. Ineffective protection from this damage leads to genetic instability which can ultimately give rise to somatic disease, causing mutations. Therefore our organism commands a number of highly conserved and effective mechanisms responsible for DNA repair. If these repair mechanisms are defective due to germline mutations in relevant genes, rare diseases with DNA repair deficiencies can arise. Today, a limited number of rare hereditary diseases characterized by genetic defects of DNA repair mechanisms is known, comprising ataxia telangiectasia, Nijmegen breakage syndrome, Werner syndrome, Bloom Syndrome, Fanconi anemia, xeroderma pigmentosum, Cockayne syndrome, trichothiodystrophy. Although heterogeneous in respect to selected symptoms, these rare disorders share many clinical features such as growth retardation, neurological disorders, premature ageing, skin alterations including abnormal pigmentation, telangiectasia, xerosis cutis, pathological wound healing as well as an increased risk of developing different types of cancer. Based on the clinical similarities of symptoms as well as the predominant diagnostic technology available, many of these rare disorders were formerly classified as genodermatoses with cancer predisposition or chromosomal breakage symptoms. These pathological conditions not only severely impair patients with these rare genetic diseases but also represent symptoms affecting large parts of the general population.


Hepatic uptake of chylomicron remnants in WHHL rabbits: a mechanism genetically distinct from the low density lipoprotein receptor.
Homozygous Watanabe hereditary hyperlipidemic (WHHL) rabbits have a near-complete deficiency of low density lipoprotein (LDL) receptors in liver and other tissues. As a result, these rabbits clear LDL from plasma at an abnormally slow rate. In the current studies we show that WHHL rabbits clear chylomicrons from plasma at a normal rate. Chylomicrons are cleared by a two-step process: (i) hydrolysis of triglycerides in extrahepatic tissues to yield cholesteryl ester-rich remnant particles and (ii) rapid uptake of the remnants by liver. Normal and WHHL rabbits were given intravenous injections of rat chylomicrons labeled either in the lipid portion with [3H]cholesterol and [14C]palmitate or in the protein portion with [125]iodine. All radiolabeled components were removed from plasma at comparable rates in normal and WHHL rabbits. Comparable amounts of radioactivity accumulated in livers of animals from both genotypes. In vitro assays showed that liver membranes from WHHL rabbits were markedly deficient in the binding of 125I-labeled chylomicron remnants as well as 125I-labeled LDL, implying that chylomicron remnants can bind to the hepatic LDL receptor. We conclude that the rabbit liver normally has at least two genetically distinct lipoprotein uptake mechanisms, both of which recognize chylomicron remnants: (i) the LDL receptor and (ii) a specific chylomicron remnant uptake mechanism that is not measured adequately by current in vitro membrane binding assays. WHHL rabbits possess a normal chylomicron remnant uptake mechanism that allows them to clear chylomicrons from plasma at a rapid rate despite their genetic deficiency of LDL receptors.


Selective Capacitive Removal of Heavy Metal Ions from Wastewater over Lewis Base Sites of S-Doped Fe-N-C Cathodes via an Electro-Adsorption Process.
The pollution of toxic heavy metals is becoming an increasingly important issue in environmental remediation because these metals are harmful to the ecological environment and human health. Highly efficient selective removal of heavy metal ions is a huge challenge for wastewater purification. Here, highly efficient selective capacitive removal (SCR) of heavy metal ions from complex wastewater over Lewis base sites of S-doped Fe-N-C cathodes was originally performed via an electro-adsorption process. The SCR efficiency of heavy metal ions can reach 99% in a binary mixed solution [NaCl (100 ppm) and metal nitrate (10 ppm)]. Even the SCR efficiency of heavy metal ions in a mixed solution containing NaCl (100 ppm) and multicomponent metal nitrates (10 ppm for each) can approach 99%. Meanwhile, the electrode also demonstrated excellent cycle performance. It has been demonstrated that the doping of S can not only enhance the activity of Fe-N sites and improve the removal ability of heavy metal ions but also combine with heavy metal ions by forming covalent bonds of S- clusters on Lewis bases. This work demonstrates a prospective way for the selective removal of heavy metal ions in wastewater.


Convergent evolution of integration site selection upstream of tRNA genes by yeast and amoeba retrotransposons.
Transposable elements amplify in genomes as selfish DNA elements and challenge host fitness because their intrinsic integration steps during mobilization can compromise genome integrity. In gene-dense genomes, transposable elements are notably under selection to avoid insertional mutagenesis of host protein-coding genes. We describe an example of convergent evolution in the distantly related amoebozoan Dictyostelium discoideum and the yeast Saccharomyces cerevisiae, in which the D. discoideum retrotransposon DGLT-A and the yeast Ty3 element developed different mechanisms to facilitate position-specific integration at similar sites upstream of tRNA genes. Transcription of tRNA genes by RNA polymerase III requires the transcription factor complexes TFIIIB and TFIIIC. Whereas Ty3 recognizes tRNA genes mainly through interactions of its integrase with TFIIIB subunits, the DGLT-A-encoded ribonuclease H contacts TFIIIC subunit Tfc4 at an interface that covers tetratricopeptide repeats (TPRs) 7 and 8. A major function of this interface is to connect TFIIIC subcomplexes τA and τB and to facilitate TFIIIB assembly. During the initiation of tRNA gene transcription τB is displaced from τA, which transiently exposes the TPR 7/8 surface of Tfc4 on τA. We propose that the DGLT-A intasome uses this binding site to obtain access to genomic DNA for integration during tRNA gene transcription.


Characterization of hormone-dependent suppressor cells in the uterus of mated and pseudopregnant mice.
The survival of the implanted "fetal allograft" has been attributed to the action of local decidua-associated suppressor cells. These suppressor cells are Fc-receptor positive small lymphocytic cells lacking T-cell markers which arise following implantation, are localized at the implantation site, and block the action of IL-2 that stimulates NK and T effector cells. Kinetic studies have demonstrated the occurrence of an earlier peak of suppressive activity occurring 2-3 days after mating prior to implantation. The cells associated with pre-implantation suppression differs significantly from post-implantation suppressor cells. Velocity sedimentation studies show that early suppression is associated with large cells sedimenting at a modal velocity of 6-7 mm/hr. Suppressive activity from cells of similar size is also present in the uterine lining of hormonally-treated, pseudopregnant mice. In addition, suppressor cells can be demonstrated in the non-pregnant uterus at the time of estrus. These observations suggest suppressor cell activity may be hormonally regulated. The suppressor cell(s) in pseudopregnant mice bears Lyt 2.1 and Thy 1.2 surface antigens and suppressor(s) present in the pregnant animals bears Lyt 2.1 and Lyt 1.1. Although the suppressor cell was large, it did not appear to be a macrophage because it was resistant to antibodies to Mac-1 and FcR cell surface markers but susceptible to anti-T cell reagents. Furthermore, suppression was not mediated by a soluble factor that has been associated with the small lymphocytic suppressor. Thus, the suppressor activity present in the pre-implantation uterine lining appears to differ significantly from the suppressor cell activity found after implantation. The possible role of a hormone-activated suppressor T cell in the success of the pregnancy is discussed.


Analysis and evaluation of the biofidelity of the human body finite element model in lateral impact simulations according to ISO-TR9790 procedures.
The biofidelity of the Ford Motor Company human body finite element (FE) model in side impact simulations was analyzed and evaluated following the procedures outlined in ISO technical report TR9790. This FE model, representing a 50th percentile adult male, was used to simulate the biomechanical impact tests described in ISO-TR9790. These laboratory tests were considered as suitable for assessing the lateral impact biofidelity of the head, neck, shoulder, thorax, abdomen, and pelvis of crash test dummies, subcomponent test devices, and math models that are used to represent a 50th percentile adult male. The simulated impact responses of the head, neck, shoulder, thorax, abdomen, and pelvis of the FE model were compared with the PMHS (Post Mortem Human Subject) data upon which the response requirements for side impact surrogates was based. An overall biofidelity rating of the human body FE model was determined using the ISO-TR9790 rating method. The resulting rating for the human body FE model was 8.5 on a 0 to 10 scale with 8.6-10 being excellent biofidelity. In addition, in order to explore whether there is a dependency of the impact responses of the FE model on different analysis codes, three commercially available analysis codes, namely, LS-DYNA, Pamcrash, and Radioss were used to run the human body FE model. Effects of these codes on biofidelity when compared with ISO-TR9790 data are discussed. Model robustness and numerical issues arising with three different code simulations are also discussed.


Self-Reported Cannabis Use Is Not Associated With Increased Opioid Use or Costs After Hip Arthroscopy.
Our purpose is to determine the difference in cost, opioid use, and complication rates following hip arthroscopy with or without perioperative cannabis use. Data were collected from a large commercial insurance database (PearlDiver) between the years 2010 and 2019. Patients who underwent hip arthroscopy with reported cannabis use were identified using Common Procedural Terminology codes and the appropriate International Classification of Diseases codes. This group was then matched by age, procedure, gender, Charleston Comorbidity Index, Elixhauser Comorbidity Index), obesity, tobacco use, diabetes to a group of similar patients without self-reported cannabis use. Opioid use over the episode of care, evaluated by morphine milligram equivalents (MME), and 30-day cost were compared between groups using unequal variance t-test. Of queried patients, 360 (.71%) had a diagnosis of preoperative cannabis use, abuse, or dependence within 5 years prior to their hip arthroscopy. A total of 300 patients (172 female, 128 male) were matched into each hip arthroscopy group, with and without cannabis. Of those patients, 171 without cannabis use and 174 with cannabis use had full financial and opioid use data for analysis. Prescription opioid use was not significantly different over the episode of care in patients with reported cannabis use (1,840 ± 2,743 MME) than those without reported cannabis use (2,129 ± 3,383 MME) (P = .3848). Additionally, episode of care reimbursement cost following hip arthroscopy did not differ significantly between patients with cannabis use ($2957 ± $4428) and those without reported cannabis use ($2,651 ± $3,762) (P = .3620). Following hip arthroscopy, patients with reported cannabis use do not appear to have significantly different postoperative opioid use or cost of hip arthroscopy episode of care compared with patients without reported cannabis use. III, cohort study.


Spinal reflex pattern to foot nociceptive stimulation in standing humans.
Ipsi- and contralateral patterns of lower limb nociceptive reflex responses were studied in 6 normal subjects in free standing position. Once the position was stabilized, only ankle extensor muscles showed consistent tonic activity while ankle flexors and knee extensors and flexors were virtually silent. Reflex responses, elicited by painful electrical stimuli to the skin of the plantar and dorsal aspect of the foot, were recorded from ipsi- and contralateral quadriceps (Q), biceps femoris (Bic), tibialis anterior (TA) and soleus (Sol) muscles. Plantar foot stimulation evoked a large excitatory response in the ipsilateral TA at about 80 ms and a smaller responses in Bic and Q at 70 ms and 110 ms, respectively. Ipsilateral excitatory effects after dorsal foot stimulation consisted of a Bic response at about 75 ms. In addition to excitatory effects, both plantar and dorsal foot stimulation evoked long-lasting suppression of ipsilateral Sol background activity starting at about 60 ms. Contralaterally, the only nociceptive effects after plantar or dorsal foot stimulation were a small excitatory response of Sol at about 85 ms. Evidence is provided that only excitatory responses were contingent upon nociceptive volley. The main mechanical effects seen after plantar stimulation were dorsiflexion of the foot without loss of heel contact with the floor; no withdrawal response of the foot followed nociceptive dorsal stimulation. Our main conclusion is that only reflex nociceptive responses serving to avoid the stimulus without conflicting with limb support function are expressed. The mechanisms reconciling nociceptive action and postural function of the lower limbs are discussed.


[Inhibition of phospholipase C gamma1 signaling pathway promotes apoptosis of human colorectal carcinoma cells].
To investigate the effects of inhibiting phospholipase C gamma1 signaling pathway on the apoptosis of human colorectal carcinoma cells. SW620 cells were treated with U73122 in vitro to inhibit the phospholipase C gamma1 signalling pathway and examined under light microscope and transmission electron microscope for analyzing changes in apoptotic behavior of the cells. MTT assay was used to evaluate the cell killing effects, and the percentage of apoptotic cells analyzed using flow cytometry. After inhibition of the phospholipase C gamma1 signaling pathway by U73122, SW620 cells exhibited obvious apoptotic morphology, the viable cells decreased dramatically, and the percentage of apoptotic cells rose to above 50%. Inhibition of phospholipase C gamma1 signaling pathway can induce apoptosis of human colorectal carcinoma cells.


[Immobilization of Penicillium vitale Pidopl. et Bilai catalase by inorganic carriers].
An efficient method is developed for P. vitale catalase immobilization through the oxidized carbohydrate enzyme component, using silochrome. The method provides the enzyme binding without losing its catalytic capacity in the immobilized preparation. When the enzyme is immobilized by high-dispersed silica containing isocyanate, aldehyde groups or active atoms of chlorine, 8, 15, and 20 mg of the enzyme is bounded per 1 g of the carrier, respectively, its catalytic capacity being completely retained. A dependence is established for the degree of catalase bonding and catalytic capacity of the immobilized enzyme of the enzyme carrier ratio in immobilization. The catalytic activity of the immobilized catalase preparations reaches 2 000 Becker units/l g. The preparations are stable in storage. Some of their properties are studied.