A Model Medical Student-Led Interprofessional QI Project on Lab Monitoring.
Teaching quality improvement (QI) in undergraduate medical education to meet entrustable professional activities (EPA) requirements is a challenge. We describe a model where first-year medical students learn QI methods using online modules and then apply their knowledge by leading an interprofessional project in a clinical setting. This model project, set in an outpatient family medicine clinic, sought to improve patient compliance with the preventive care metric of annual serum potassium and creatinine monitoring for patients taking a diuretic, angiotensin-converting enzyme inhibitor (ACEI), or angiotensin receptor blocker (ARB) medication. A first-year medical student joined an interprofessional team of one primary care physician and three pharmacy residents. The student led the team in reviewing patient charts to identify root causes and implementing a multifaceted strategy to improve patient outreach and refill policies. The effects of these interventions were monitored weekly using an electronic health record population health tool (Epic's Healthy Planet) over the course of 10 months. At baseline, 76.7% (477/622) of patients taking a diuretic and 79.4% (752/947) taking an ACEI or ARB were compliant with monitoring, approximately 10% below the Healthcare Effectiveness Data and Information Set (HEDIS) recommendations. Within 6 months, interventions resulted in both patient cohorts meeting the HEDIS metric with sustained success for the study duration of 10 months. This report demonstrates that a first-year medical student can make meaningful contributions to preventive care while gaining clinically relevant QI experience. Further evaluation is needed to determine generalizability and scalability of this model.


The application of ultraviolet germicidal irradiation to control transmission of airborne disease: bioterrorism countermeasure.
Bioterrorism is an area of increasing public health concern. The intent of this article is to review the air cleansing technologies available to protect building occupants from the intentional release of bioterror agents into congregate spaces (such as offices, schools, auditoriums, and transportation centers), as well as through outside air intakes and by way of recirculation air ducts. Current available technologies include increased ventilation, filtration, and ultraviolet germicidal irradiation (UVGI) UVGI is a common tool in laboratories and health care facilities, but is not familiar to the public, or to some heating, ventilation, and air conditioning engineers. Interest in UVGI is increasing as concern about a possible malicious release of bioterror agents mounts. Recent applications of UVGI have focused on control of tuberculosis transmission, but a wide range of airborne respiratory pathogens are susceptible to deactivation by UVGI. In this article, the authors provide an overview of air disinfection technologies, and an in-depth analysis of UVGI-its history, applications, and effectiveness.


Immune response in pigs vaccinated with plasmid DNA encoding ORF5 of porcine reproductive and respiratory syndrome virus.
The ORF5-encoded major envelope glycoprotein (GP5) of porcine reproductive and respiratory syndrome virus (PRRSV) is one of the three major structural proteins of this virus. While some porcine convalescent sera and monoclonal antibodies directed against GP4 and GP5 have the capacity to neutralize the virus in vitro, the protein specificity of porcine neutralizing sera has not yet been established. DNA immunization with a plasmid encoding GP5 of PRRSV, under the control of a human cytomegalovirus promoter, induced anti-GP5-specific neutralizing antibodies in pigs and BALB/c mice. The GP5 protein specificity of neutralizing sera was confirmed by immunoblotting and ELISA. Peripheral blood mononuclear cells obtained from DNA-vaccinated pigs underwent blastogenic transformation in the presence of E. coli-expressed recombinant ORF5-encoded protein, indicating the specificity of the cellular immune response to GP5. Following a massive intratracheal challenge with the virulent IAF-Klop strain of PRRSV, DNA-vaccinated pigs were protected from generalized viraemia and the development of typical macroscopic lung lesions that were observed in unvaccinated, virus-challenged controls, as well as in pigs that were immunized with E. coli-expressed GST-ORF5 recombinant fusion protein. Interstitial pneumonitis and broncho-alveolitis were remarkably milder in DNA-vaccinated animals. These results suggest that the GP5 of PRRSV is a good candidate for a subunit recombinant-type vaccine.


Hypoactive-hypoalert behaviour and thalamic hypometabolism due to intracranial hypotension.
A 47-year-old man presented with a 9-year history of a hypoalert hypoactive behaviour syndrome, caused by the deep brain swelling variant of spontaneous intracranial hypotension. Along with apathy with retained cognition, he had stable ataxia, impaired upgaze and episodes of central apnoea. MRI brain showed a sagging brainstem, pointed ventricles and reduced angle between the vein of Galen and the straight sinus, but no meningeal enhancement or subdural collections. A dopamine transporter scan showed preganglionic dopamine receptor deficiency; a fluorodeoxy glucose positron emission tomography scan showed bilateral hypothalamic hypometabolism. This variant of spontaneous intracranial hypotension may alter deep brain functioning within the basal ganglia and thalamus, causing the hypoactive-hypoalert behaviour phenotype.


Post-infarction inflammation and left ventricular remodeling: a double-edged sword.
After myocardial infarction (MI), inflammatory cells such as neutrophils, followed by monocytes and macrophages, infiltrate and phagocytose the necrotic tissues, as well as secreting a variety of inflammatory cytokines. The vulnerable myocardium, which consists of necrotic tissue and inflammatory cells, is susceptible to wall stress, resulting in infarct expansion. Subacute cardiac rupture is an extreme form of infarct expansion, whereas ventricular aneurysm is its chronic form and a trigger for subsequent left ventricular (LV) remodeling. Although post-infarction inflammation is essential for the healing process, excessive inflammation could play an important role in the development of LV remodeling. Increase in the C-reactive protein level, which reflects myocardial inflammation, is reported to be a useful predictive marker for cardiac rupture, ventricular aneurysm and LV remodeling. In addition, an increase in peripheral monocyte count is associated with a poor outcome after MI, and an animal study has demonstrated that granulocyte/macrophage-colony stimulating factor induction causes excessive macrophage infiltration in the infarcted area and worsening of LV remodeling. Recently, it was also found that dendritic cells play an important role in controlling excessive inflammation caused by monocytes/macrophages. Thus, inflammation that develops after MI is a double-edged sword, and how to control inflammation to suppress pathological remodeling is an important issue to be considered in developing new treatment for heart failure.


Isolation and characterization of an aspartic protease from Salpichroa origanifolia fruits.
This report describes the purification of an aspartic protease (salpichroin) from ripe fruits of Salpichroa origanifolia (Solanaceae) starting with precipitation using organic solvents and anionexchange chromatography with 32.1% recovery and 13.4-fold purification. SDS-PAGE and zymograms of this enzyme showed a single band corresponding to an apparent molecular mass of approximately 32 kDa. The biochemical and kinetic characterization of the pure enzyme showed an acidic behavior with an optimal pH value around 3.0-4.5 with hemoglobin and 5.5-6.0 with casein. Salpichroin activity was inhibited by pepstatin but not by phenylmethylsulfonyl fluoride, E-64, EDTA or 1,10-phenanthroline, thus suggesting an aspartic protease behavior. Salpichroin hydrolyzed natural substrates, such as casein and hemoglobin, with high specific activity. Kinetic studies conducted with the synthetic peptide H-Pro- Thr-Glu-Phe-p-(NO2)-Phe-Arg-Leu-OH showed lower affinity (Km 494 µM) than other representative aspartic proteases. By investigating the cleavage of oxidized insulin β-chain to establish the hydrolytic specificity of salpichroin, we found six cleavage sites on the substrate of peptide bonds similar to those of chymosin. MALDI-TOF/TOF-MS of the tryptic ingel digest of salpichroin showed that the isolated protease shared homologous sequences with other plant proteases of the A1 aspartic protease family. This is the first report concerning the isolation and biochemical characterization of an aspartic protease isolated from Salpichroa origanifolia fruits.


The association between evidence of a predator threat and responsiveness to alarm calls in Western Australian magpies (Cracticus tibicen dorsalis).
Alarm calls are a widespread form of antipredator defence and being alerted to the presence of predators by the alarm calls of conspecifics is considered one of the benefits of group living. However, while social information can allow an individual to gain additional information, it can also at times be inaccurate or irrelevant. Such variation in the accuracy of social information is predicted to select for receivers to discriminate between sources of social information. In this study, we used playback experiments to determine whether Western Australian magpies (Cracticus tibicen dorsalis) respond to the predator information associated with alarm calls. Magpies were exposed to the alarm calls of two group members that differed in the threat associated with the alarm call: one call was played in the presence of a predator model while the other was not-in order to establish differences in the predator information provided by each caller. We then played back the alarm calls of the same group members in the absence of the predator model to determine whether magpies responded differently to signallers in response to the previous association between the alarm call and a predator threat. We found that receivers showed significantly greater levels of responsiveness to signallers that previously gave alarm calls in the appropriate context. Thus, the accuracy of threat-based information influenced subsequent receiver response.


Duration of Heightened Ischemic Stroke Risk After Acute Myocardial Infarction.
Background The duration of heightened stroke risk after acute myocardial infarction ( MI ) remains uncertain. Methods and Results We performed a retrospective cohort study using claims between 2008 and 2015 from a nationally representative 5% sample of Medicare beneficiaries aged ≥66 years. Both acute MI and ischemic stroke were ascertained using previously validated International Classification of Diseases, Ninth Revision, Clinical Modification ( ICD-9-CM), diagnosis codes. To exclude periprocedural strokes from percutaneous coronary intervention, we did not count strokes occurring during an acute MI hospitalization. Patients were censored at the time of ischemic stroke, death, end of Medicare coverage, or September 30, 2015. We fit Cox regression models separately for the groups with and without acute MI to examine its association with ischemic stroke after adjustment for demographics, stroke risk factors, and Charlson comorbidities. We used the corresponding survival probabilities to compute the hazard ratio in each 4-week interval after discharge. Confidence intervals were computed using the nonparametric bootstrap method. Among 1 746 476 eligible beneficiaries, 46 182 were hospitalized for acute MI and 80 466 for ischemic stroke. After adjustment for demographics, stroke risk factors, and Charlson comorbidities, the risk of ischemic stroke was highest in the first 4 weeks after discharge from the MI hospitalization (hazard ratio: 2.7; 95% confidence interval, 2.3-3.2), remained elevated during weeks 5 to 8 (hazard ratio: 2.0; 95% confidence interval, 1.6-2.4) and weeks 9 to 12 (hazard ratio: 1.6; 95% confidence interval, 1.3-2.0), and was no longer significantly elevated afterward. Conclusions Acute MI is associated with an elevated risk of ischemic stroke that appears to extend beyond the 1-month window that is currently considered the at-risk period.


Acute kidney injury during pregnancy.
Acute kidney injury complicates the care of a relatively small number of pregnant and postpartum women. Several pregnancy-related disorders such as preeclampsia and thrombotic microangiopathies may produce acute kidney injury. Prerenal azotemia is another common cause of acute kidney injury in pregnancy. This manuscript will review pregnancy-associated acute kidney injury from a renal functional perspective. Pathophysiology of acute kidney injury will be reviewed. Specific conditions causing acute kidney injury and treatments will be compared.


[The effect of lipoproteins on signal transduction in thrombocytes and vascular wall cells].
In recent decades, studies have shown that lipoproteid physiological role goes beyond just their part in lipid transport. Database is accumulating on connection of lipoproteid pathological effects upon cardiovascular system with their ability to interfere in the signal transmission processes necessary for normal control of the vascular homeostasis. There is some evidence that lipoproteids are capable of affecting vascular tonus, coagulation balance, and inflammatory processes in the vascular wall. These effects will be realized through activation of the blood cell and vascular wall signal systems and can accelerate development of atherosclerosis and prompt hypertension and arterial thrombophilia.


Dual fluoroscopy with live-image digital zooming significantly reduces patient and operating staff radiation during fenestrated-branched endovascular aortic aneurysm repair.
Fenestrated-branched endovascular aneurysm repair (F/B-EVAR) is a complex procedure that generates high radiation doses. Magnification aids in vessel cannulation but increases radiation. The aim of the study was to compare radiation doses to patients and operating room staff from two fluoroscopy techniques, standard magnification vs dual fluoroscopy with live-image digital zooming during F/B-EVAR. An observational, prospective, single-center study of F/B-EVAR procedures using Philips Allura XperFD20 equipment (Philips Healthcare, Amsterdam, The Netherlands) was performed during a 42-month period. Intravascular ultrasound, three-dimensional fusion, and extreme collimation were used in all procedures. Intraoperative live-image processing was performed with two imaging systems: standard magnification in 123 patients (81%) and dual fluoroscopy with live-image digital zooming in 28 patients (18%). In the latter, the live "processed" zoomed images are displayed on examination displays and live images are displayed on reference displays. The reference air kerma was collected for each case and represents patient dose. Operating staff personal dosimetry was collected using the DoseAware system (Philips Healthcare). Patient and staff radiation doses were compared using nonparametric tests. Mean age was 71.6 ± 11.4 years. The median body mass index was 27 kg/m2 (interquartile range [IQR], 24.4-30.6 kg/m2) and was the same for both groups. Procedures performed with dual fluoroscopy with digital zooming demonstrated significantly lower median patient (1382 mGy [IQR, 999-2045 mGy] vs 2458 mGy [IQR, 1706-3767 mGy]; P < .01) and primary operator radiation doses (101 μSv [IQR, 34-235 μSv] vs 266 μSv [IQR, 104-583 μSv]; P < .01) compared with standard magnification. Similar significantly reduced radiation doses were recorded for first assistant, scrub nurse, and anesthesia staff in procedures performed with dual fluoroscopy. According to device design, procedures performed with four-fenestration/branch devices generated higher operator radiation doses (262 μSv [IQR, 116.5-572 μSv] vs 171 μSv [IQR, 44-325 μSv]; P < .01) compared with procedures with three or fewer fenestration/branches. Among the most complex design (four-vessel), operator radiation dose was significantly lower with digital zooming compared with standard magnification (128.5 μSv [IQR, 70.5-296 μSv] vs 309 μSv [IQR, 150-611 μSv]; P = .01). Current radiation doses to patients and operating personnel are within acceptable limits; however, dual fluoroscopy with live-image digital zooming results in dramatically lower radiation doses compared with the standard image processing with dose-dependent magnification. Operator radiation doses were reduced in half during procedures performed with more complex device designs when digital zooming was used.


[Polymorphism of human HLA-DRB1 leukocyte antigen alleles and its association to juvenile rheumatoid arthritis in a sample of Colombian mestizo children].
Oligotypes of the human leukocyte antigen HLA Class II, DRB1 alleles were characterized at the molecular level in a group of Colombian children suffering juvenile rheumatoid arthritis (JRA). The distribution of these alleles was examined in a group of Colombian mestizo children (genetic admixture of Amerindians, Europeans and Africans) suffering from clinically distinct JRA subsets in order to detect HLA allele frequency differences in patients with different JRA subsets. A group of 65 patients with JRA and 65 controls were characterized for the subtypes of the HLA-DRB1 alleles using polymerase chain reaction with sequence-specific oligonucleotide probes (PCR-SSOP). The oligotyping protocol recommended by the 12th International Histocompatibility Workshop held in St. Malo, Paris, in 1996, was used. Subtype HLA-DRB1*1104 was the allele most strongly associated with susceptibility to JRA (Fisher's p = 0.013, odds ratio (OR) = 16.79, etiologic fraction (EF) = 0.93). HLA-DRB1*1602 was also associated with susceptibility to a lesser degree (Fisher's p = 0.016, OR = 8.98, EF = 0.88). HLA-DRB1 alleles participating in JRA protection were HLA-DRB1*1501 (preventive fraction (PF) = 0.466, p = 0.005) and HLA DRB1*1402 (PF = 0.49, p = 0.009). The relationship between some HLA-DRB1 alleles and clinical features was also compared. The presence of rheumatic factor was associated with the alleles HLA-DRB1*0407 (p = 0.05, OR = 11.2, EF = 0.45) and HLA-DRB1*1302 (p = 0.02, OR = 22.8, EF = 0.63). There was also an association between HLA-DRB1*0701 (p = 0.001, OR = 58, EF = 0.73) with expressing ANA +. We found that in the oligoarticular subset, the allele HLA-DRB1*1104 (p = 0.0034, OR = 41.53, EF = 0.97) was the one expressed most commonly. In the poliarticular group, the alleles most frequently expressed were HLA-DRB1*0404 (Fisher's p = 0.012, OR = 8.75, EF = 0.88). In patients with systemic JRA, the HLA-DRB1*1602 allele (p = 0.005, OR = 21.33, EF = 0.95) was most frequent. These results suggested that the MHC genes of mestizo children influence not only the clinical expression of the disease, but also the susceptibility to its development.


Autoantibody-mediated arthritis in the absence of C3 and activating Fcγ receptors: C5 is activated by the coagulation cascade.
The effector functions of immunoglobulin G (IgG) are mediated by interaction of its Fc region with Fc receptors (FcγRs) and/or the complement system. The three main pathways of complement activation converge at C3. However, C3-independent pathways can activate C5 and other downstream complement components during IgG-initiated inflammatory responses. These C3-independent pathways of C5 activation are triggered by activating FcγRs in some systems or can be activated by factors of the coagulation cascade such as thrombin. Here we studied the interplay of C3, C5, and activating FcγRs in a model of spontaneous autoantibody-driven arthritis. We utilized the K/BxN TCR transgenic mouse model of arthritis. We bred K/BxN mice bearing targeted or naturally-occurring mutations in one or more of the genes encoding complement components C3, C5, and FcRγ, the cytoplasmic signaling chain shared by the activating FcγRs. We measured arthritis development, the production of arthritogenic autoantibodies, T cell activation status and cytokine synthesis. In addition, we treated mice with anti-C5 monoclonal antibodies or with the thrombin inhibitor argatroban. We have previously shown that genetic deficiency of C5 protects K/BxN mice from the development of arthritis. We found here that C3-deficient K/BxN mice developed arthritis equivalent in severity to C3-sufficient animals. Arthritis also developed normally in K/BxN mice lacking both C3 and FcRγ, but could be ameliorated in these animals by treatment with anti-C5 monoclonal antibody or by treatment with argatroban. Production of arthritogenic autoantibodies, T cell activation, and T cell cytokine production were not affected by the absence of C3, C5, and/or FcRγ. In K/BxN mice, C5-dependent autoantibody-driven arthritis can occur in the genetic absence of both complement C3 and activating FcγRs. Our findings suggest that in this setting, thrombin activates C5 to provoke arthritis.


Hydroxyapatite growth induced by native extracellular matrix deposition on solid surfaces.
Biological systems have a remarkable capability to produce perfect fine structures such as seashells, pearls, bones, teeth and corals. These structures are composites of interacting inorganic (calcium phosphate or carbonate minerals) and organic counterparts. It is difficult to say with certainty which part has the primary role. For example, the growth of molluscan shell crystals is thought to be initiated from a solution by the extracellular organic matrix (ECM). According to this theory, the matrix induces nucleation of calcium containing crystals. Recently, an alternative theory has been put forward, stating that a class of granulocytic hemocytes would be directly involved in shell crystal production in oysters. In the work presented here the surface of AISI 316 stainless steel was modified by deposition of ECM proteins. The ability of the modified substrates to induce nucleation and growth of hydroxyapatite (HA) from simulated body fluid (SBF) was examined by a kinetic study using two methods: (1) a simple soaking process in SBF and (2) a laser-liquid-solid interaction (LLSI) process which allows interaction between a scanning laser beam and a solid substrate immersed in SBF. The deposited HA layers were investigated by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). It was found that a coating of stainless steel surface with native ECM proteins induced nucleation and growth of HA and facilitated its crystallization. By the process of simple soaking of the samples, irrespective of their horizontal or vertical position in the solution, HA layers were grown due to the reactive ECM-coated stainless steel surface. It was shown that the process occurring in the first stages of the growth was not only a result of the force of gravity. The application of the LLSI process strongly influenced HA formation on the ECM-modified substrates by promoting and enhancing the HA nucleation and growth through a synergistic effect of a few stimuli, i.e., the modified solid surface, the laser beam and the aqueous solution.


Differentiation of mild keratoconus from corneal warpage according to topographic inferior steepening based on corneal tomography data.
We report two cases of suspicious asymmetric bow tie and inferior steepening on topographic evaluations with reflection (Placido) and projection (Scheimpflug). Rotating Scheimpflug corneal and anterior segment tomography (Oculus Pentacam HR, Wetzlar, Germany)® was performed in the first case, with a maximal keratometric value (Kmax) of 43.2 D and an overall deviation value from the Belin/Ambrósio Enhanced Ectasia Display (BAD-D) of 1.76, which was observed in the study eye (OD). BAD-D was 6.59 in the fellow eye, which had clinical findings that were consistent with keratoconus stage 2. The second case presented with a Kmax of 45.3 D and BAD-D of 0.76 in OD and 1.01 in OS. This patient had discontinued wearing soft contact lens less than 1 day prior to examination. Corneal tomographic data enabled us to distinguish mild or forme fruste keratoconus from contact lens-induced corneal warpage, and similar findings were observed on curvature maps.


Switching terahertz wave with grating-coupled Kretschmann configuration.
We present a terahertz wave switch utilizing Kretschmann configuration which consists of high-refractive-index prism-liquid crystal-periodically grooved metal grating. The switching mechanism of the terahertz switch is based on spoof surface plasmon polariton (SSPP) excitation in the attenuated total reflection regime by changing the liquid crystal refractive index. The results highlighted the fact that the feasibility to "tune" the attenuated total reflection terahertz wave intensity by using the external applied bias voltage. The extinction ratio of the terahertz switch reaches 31.48dB. The terahertz switch has good control ability and flexibility, and can be used in potential terahertz free space device systems.


Idiopathic necrotizing fasciitis following fracture fixation: A case report.
Idiopathic necrotizing fasciitis (NF) is an infrequent, highly lethal skin infection that spreads rapidly, marked by fascia and subcutaneous tissue necrosis. It occurs in the absence of a known causative factor. Its emergence after sterile orthopedic fixation with unexpected spread to the abdomen may turn to be challenging both as a medical and surgical emergency. A 56-year-old diabetic female presented with multiple fractures. After open reduction and internal fixation (ORIF) with iliac crest grafting of hip fracture, she developed incisional NF which later spread to the abdomen. Post-ORIF of hip fracture complicated with idiopathic NF and abdominal spread. She underwent emergency débridements with negative pressure wound therapy and broad-spectrum intravenous antibiotic therapy. After granulation, the wounds were closed with skin flaps and grafts with antibiotic beads. When the NF spread to the abdomen, additional débridements during abdominal explorations were performed. The patient was initially stable with promising healings of the wounds. Later, the patient suddenly developed a high fever and severe abdominal pain. Ultrasound revealed that NF emerged unexpectedly in the right lower abdomen. The causative agent of the NF remained undetected. Despite all the extensive treatments, the patient's condition deteriorated rapidly. She died of septic shock and multiple organ failure. The idiopathic NF may still potentially occur after a clean ORIF of the hip region. The implementation of intensive guideline-based treatments may show improvements, but the risk of unexpected NF spread to the abdomen should be anticipated, which may increase the mortality rates in diabetic or immunocompromised patients.


Effect of an elastin growth substrate on cholesteryl ester synthesis and foam cell formation by cultured aortic smooth muscle cells.
Exposure of smooth muscle cells cultured on plastic or glass to hyperlipidemic serum did not result in the formation of foam cells. Since elastin binds serum lipids, and vascular smooth muscle cells are normally closely associated with elastin, we investigated the effects of an elastin substrate on lipid metabolism and on the accumulation of lipid vacuoles by rabbit aortic smooth muscle cells in culture. When cells were grown in plastic petri dishes, cholesteryl ester synthesis, as measured by [14C]oleate incorporation into cholesteryl esters, was 3 times greater in rabbit hyperlipidemic serum (HLS) than in normolipemic serum (NLS) (P less than 0.001). For cells of the same subculture grown on the elastin substrate, the synthetic rate was 6-fold greater in HLS compared to NLS (P less than 0.005). The cells grown on the elastin membranes in the presence of HLS contained large numbers of Oil red O stainable lipid vacuoles and resembled foam cells, while those grown in petri dishes and exposed to HLS showed only an occasional cell containing a few vacuoles. Pre-incubation in lipoprotein-deficient serum markedly enhanced the stimulatory effect of HLS on cholesteryl ester synthesis for cells growing in plastic petric dishes but had much less stimulatory effect on the cells growing on elastin membranes. These studies indicate that close association with elastin modulates the response of smooth muscle cells to hyperlipidemia and suggest a role for elastin in the formation of foam cells of smooth muscle origin during atherogenesis.


Characterization of infectious salmon anemia virus, an orthomyxo-like virus isolated from Atlantic salmon (Salmo salar L.).
Infectious salmon anemia (ISA) virus is the cause of infectious salmon anemia in farmed Atlantic salmon. The virus has been shown to contain RNA with structural characteristics similar to those of accepted members of the Orthomyxoviridae. Further biochemical, physiochemical, and morphological characterization of ISA virus was undertaken to clarify its taxonomic position. The virus was found to be sensitive to chloroform, heat, and low pH and agglutinated erythrocytes from fish. Erythrocytes from mammals or birds were not agglutinated. Receptor-destroying enzyme activity was detected, and the nature of this enzyme was suggested to be an acetylesterase. The buoyant density of the virus was 1.18 g/ml in sucrose and CsCl gradients. The maximum rate of virus replication was observed at 15 degrees C, while no virus was produced at 25 degrees C. Actinomycin D inhibited viral replication, and viral antigen was detected in nuclei by immunofluorescence. The addition of trypsin to the culture medium during virus replication had a beneficial effect on virus replication. ISA virus contains four major polypeptides with estimated molecular sizes of 71, 53, 43, and 24 kDa. Electron microscopy revealed structures closely resembling the nucleocapsids of influenza virus. Mushroom-shaped surface projections were a distinctive morphological feature, which differed from the rod-shaped hemagglutinin projections of the influenza viruses. The data reported here support the relationship of ISA virus to the Orthomyxoviridae, although ISA virus differs from influenza viruses in some morphological characteristics and in showing restricted hemagglutination, in different specificity of the receptor-destroying enzyme, in different polypeptide profile, in being unable to replicate at temperatures above 25 degrees C, and in host range.


Advanced stage of oral myiasis in children: a clinical case report.
Human myiasis is characterized by larval infestation of body tissues or cavities of live individuals. Although most frequently observed in underdeveloped and tropical countries, reports of human myiasis have been encountered throughout the world. Conventional treatment is the mechanical removal of the larvae, one by one, which is painful and embarrassing and repugnant to both health professional and patient. Even though human myiasis is not considered rare, most dental professionals have very little knowledge of the diagnosis and treatment of this pathology. The purpose of this article, therefore, is to report a case of advanced-stage oral myiasis in a 9-year-old patient treated at a health and dentistry clinic. Diagnosis was based on visual observation of Cochliomyia hominivorax larvae, a dipterous fly of the Calliphoridae family, which were between the second and third stages of development. Predisposition factors include lack of information, malnutrition, poor oral hygiene, preexistence of oral lesions, and severe halitosis, which decisively influence the appearance and development of oral myiasis. A brief review of the literature is also included, in which the importance of early clinical diagnosis, myiasis etiology, and possible associations with other pathologies and different types of treatment are discussed.


Patient Experiences With Outpatient Parenteral Antibiotic Therapy: Results of a Patient Survey Comparing Skilled Nursing Facilities and Home Infusion.
This work compares overall patient satisfaction with outpatient parenteral antibiotic therarpy (OPAT) care across the skilled nursing facility (SNF) and home healthcare company (HHC) settings; identifies barriers to patient satisfaction in OPAT; and develops a model for OPAT patient satisfaction that can help programs improve the patient experience across both sites of care. We developed and administered a patient experience survey to 100 patients returning to a single clinic for follow up. The survey consisted of 15 items (Likert scale, multiple choice, and free text responses). Patient characteristics and responses to the survey for patients who received care at home and at SNFs were analyzed and compared. Of the 100 patients surveyed, 98 completed the survey. Overall, HHC patients were satisfied more with their care than patients in SNFs, with a greater proportion stating they would recommend the site to others (71.7% for HHC and 32.7% for SNFs, P < .01). Patients in SNFs had a larger number of complaints about lapses in medical care, infection prevention, and the physical environment than HHC patients. Patient satisfaction in OPAT is higher for home infusion than SNFs. In order to improve the patient experience, OPAT programs need to engage stakeholders in HHCs and SNFs to improve communication and care delivery.


Accuracy of digital image enhancement in detection of vertical and horizontal root fracture.
Two-dimensional intraoral radiography is the most common tool for recognizing root fractures. Improving the quality of images by means of enhancement tools can increase the recognition power of them. The aim of this study is to evaluate the effect of digital image enhancement on vertical and horizontal root fractures (HRFs) diagnostic accuracy. In this in vitro study, 100 human extracted teeth, involving 50 mandibular premolars and 50 maxillary incisors, were investigated. In total, 25 premolar teeth were vertically fractured and other 25 sound teeth served as testing group. According to the verified methods, 25 incisor teeth were fractured and other 25 teeth of this group served as testing ones. Following, by using the charge-coupled device sensor, preapical digital images were recorded. The original images were altered using reverse-contrast and colorization enhancement tools. Two different observers independently investigated all of the images. Receiver operating characteristic analysis was used to calculate the area under the curve (AUC) and sensitivity and specificity of all images. Data analyzde using receiver operating characteristic (ROC) analysis. Two-ways variance analysis was used to assess differences in the values (P = 0.05 ). AUC and sensitivity and specificity related to the original, reverse-contrast, and colorized images were calculated (0.84, 0.64, 0.99), (0.84, 0.64, 0.96), and (0.82, 0.64, 0.92) respectively, for vertically root fractured images. AUC and sensitivity and specificity related to the original, reverse-contrast, and colorized images were calculated (0.49, 0.44, 0.56), (0.50, 0.44, 0.60), and (0.48, 0.48, 0.48), respectively, for horizontally root-fractured images. The results of the present study revealed that reverse-contrast and colorized enhancement filters cannot be used as critical methods in detecting in vitro vertical and HRF.


The congenital disorders of glycosylation: a multifaceted group of syndromes.
The congenital disorders of glycosylation (CDG) are a rapidly expanding group of metabolic syndromes with a wide symptomatology and severity. They all stem from deficient N-glycosylation of proteins. To date the group contains 18 different subtypes: 12 of Type I (disrupted synthesis of the lipid-linked oligosaccharide precursor) and 6 of Type II (malfunctioning trimming/processing of the protein-bound oligosaccharide). Main features of CDG involve psychomotor retardation; ataxia; seizures; retinopathy; liver fibrosis; coagulopathies; failure to thrive; dysmorphic features, including inverted nipples and subcutaneous fat pads; and strabismus. No treatment currently is available for the vast majority of these syndromes (CDG-Ib and CDG-IIc are exceptions), even though attempts to synthesize drugs for the most common subtype, CDG-Ia, have been made. In this review we will discuss the individual syndromes, with focus on their neuronal involvement, available and possible treatments, and future directions.


Regioselective synthesis of beta-N1- and beta-N3-alloxazine nucleosides
[structures: see text] A regio- and stereoselective glycosylation of ribose tetraester with persilylated alloxazine to give either beta-N1 or beta-N3 nucleosides is described. The N3 product is potentially of interest as a fluorescent nucleoside and is predicted to have the hydrogen-bonding characteristics of thymidine.


Limit laws for the asymmetric inclusion process.
The Asymmetric Inclusion Process (ASIP) is a unidirectional lattice-gas flow model which was recently introduced as an exactly solvable 'Bosonic' counterpart of the 'Fermionic' asymmetric exclusion process. An iterative algorithm that allows the computation of the probability generating function (PGF) of the ASIP's steady state exists but practical considerations limit its applicability to small ASIP lattices. Large lattices, on the other hand, have been studied primarily via Monte Carlo simulations and were shown to display a wide spectrum of intriguing statistical phenomena. In this paper we bypass the need for direct computation of the PGF and explore the ASIP's asymptotic statistical behavior. We consider three different limiting regimes: heavy-traffic regime, large-system regime, and balanced-system regime. In each of these regimes we obtain-analytically and in closed form-stochastic limit laws for five key ASIP observables: traversal time, overall load, busy period, first occupied site, and draining time. The results obtained yield a detailed limit-laws perspective of the ASIP, numerical simulations demonstrate the applicability of these laws as useful approximations.


Generative Adversarial Networks and Conditional Random Fields for Hyperspectral Image Classification.
In this paper, we address the hyperspectral image (HSI) classification task with a generative adversarial network and conditional random field (GAN-CRF)-based framework, which integrates a semisupervised deep learning and a probabilistic graphical model, and make three contributions. First, we design four types of convolutional and transposed convolutional layers that consider the characteristics of HSIs to help with extracting discriminative features from limited numbers of labeled HSI samples. Second, we construct semisupervised generative adversarial networks (GANs) to alleviate the shortage of training samples by adding labels to them and implicitly reconstructing real HSI data distribution through adversarial training. Third, we build dense conditional random fields (CRFs) on top of the random variables that are initialized to the softmax predictions of the trained GANs and are conditioned on HSIs to refine classification maps. This semisupervised framework leverages the merits of discriminative and generative models through a game-theoretical approach. Moreover, even though we used very small numbers of labeled training HSI samples from the two most challenging and extensively studied datasets, the experimental results demonstrated that spectral-spatial GAN-CRF (SS-GAN-CRF) models achieved top-ranking accuracy for semisupervised HSI classification.


SCAN: A Scalable Model of Attentional Selection.
This paper describes the SCAN (Signal Channelling Attentional Network) model, a scalable neural network model for attentional scanning. The building block of SCAN is a gating lattice, a sparsely-connected neural network defined as a special case of the Ising lattice from statistical mechanics. The process of spatial selection through covert attention is interpreted as a biological solution to the problem of translation-invariant pattern processing. In SCAN, a sequence of pattern translations combines active selection with translation-invariant processing. Selected patterns are channelled through a gating network, formed by a hierarchical fractal structure of gating lattices, and mapped onto an output window. We show how the incorporation of an expectation-generating classifier network (e.g. Carpenter and Grossberg's ART network) into SCAN allows attentional selection to be driven by expectation. Simulation studies show the SCAN model to be capable of attending and identifying object patterns that are part of a realistically sized natural image. Copyright 1997 Elsevier Science Ltd.


Ultraviolet irradiation induces CYR61/CCN1, a mediator of collagen homeostasis, through activation of transcription factor AP-1 in human skin fibroblasts.
UV irradiation from the sun elevates the production of collagen-degrading matrix metalloproteinases (MMPs) and reduces the production of new collagen. This imbalance of collagen homeostasis impairs the structure and function of the dermal collagenous extracellular matrix (ECM), thereby promoting premature skin aging (photoaging). We report here that aberrant dermal collagen homeostasis in UV-irradiated human skin is mediated in part by a CCN-family member, cysteine-rich protein-61 (CYR61/CCN1). CYR61 is significantly elevated in acutely UV-irradiated human skin in vivo, and UV-irradiated human skin fibroblasts. Knockdown of CYR61 significantly attenuates UV irradiation-induced inhibition of type-I procollagen and upregulation of MMP-1. Determination of CYR61 mRNA and protein indicates that the primary mechanism of CYR61 induction by UV irradiation is transcriptional. Analysis of CYR61 proximal promoter showed that a sequence conforming to the consensus binding site for transcription factor activator protein-1 (AP-1) is required for promoter activity. UV irradiation increased the binding of AP-1-family members c-Jun and c-Fos to this AP-1 site. Furthermore, functional blockade of c-Jun or knockdown of c-Jun significantly reduced the UV irradiation-induced activation of CYR61 promoter and CYR61 gene expression. These data show that CYR61 is transcriptionally regulated by UV irradiation through transcription factor AP-1, and mediates altered collagen homeostasis that occurs in response to UV irradiation in human skin fibroblasts.


Role of angiotensin-converting enzyme in Bacille Calmette-Guérin-induced granulomatous inflammation. Increased angiotensin-converting enzyme levels in lung lavage and suppression of inflammation with captopril.
Lung lavage levels of angiotensin-converting enzyme (ACE)-like activity were increased in C57BL/6 mice with Bacille Calmette-Guérin (BCG)-induced chronic granulomatous pulmonary inflammation and splenomegaly. Contrariwise, ACE activity was not increased in lung lavage fluids of CBA mice that developed only minimal pulmonary inflammation in response to BCG. ACE-like activity correlated with the intensity of inflammation and Captopril, a specific competitive inhibitor of ACE activity, markedly suppressed the induction and maintenance of the BCG-induced inflammatory response in both lungs and spleen. It was necessary, however, to provide sustained treatment with large doses of Captopril in order to reduce the inflammatory response. After a single intraperitoneal injection of Captopril, ACE levels in lung lavage of BCG-injected mice were reduced but returned to preinjection levels or greater within 24 h. The highest dose of Captopril was more effective in reducing the lung fluid level of ACE in BCG-inflamed lungs. This suggests that sustained daily injections of Captopril were necessary to maintain reduced ACE levels. In vitro studies indicated that high concentrations of Captopril did not affect macrophage mobility or chemotactic activity for macrophages. Thus, ACE may act as a molecular mediator of BCG-induced granulomatous inflammation in the lung.


Sixth Cranial Nerve Palsy as the Presenting Sign of Metastatic Cholangiocarcinoma.
Cholangiocarcinoma is a locally invasive, poorly treatable malignancy of the biliary tract that uncommonly metastasizes to the brain and rarely causes neuro-ophthalmologic complications. A 34-year-old woman with an isolated sixth cranial nerve palsy underwent brain neuroimaging and was found to have a large sellar/suprasellar mass invading the cavernous sinus. Gross total resection was performed with improvement in the sixth cranial nerve nerve palsy. Next-generation sequencing and histology studies revealed an adenocarcinoma with a fibroblast growth factor receptor (FGFR)2-BICC1 gene mutation. Positron emission tomography/computed tomography scan demonstrated a large hypermetabolic partially necrotic hepatic mass with local invasion, and liver biopsy confirmed a diagnosis of cholangiocarcinoma. At three weeks after resection, the brain lesion recurred and the patient developed worsening diplopia. The patient then received stereotactic radiotherapy applied to the brain lesion and began treatment with gemcitabine and cisplatin. The patient was transitioned to FGFR-targeted therapy with pemigatinib, and the patient was alive at last follow-up, 49 weeks after diagnosis. To our knowledge, this is the first report of cholangiocarcinoma presenting as a neuro-ophthalmologic finding, consisting of an isolated sixth cranial nerve palsy, which was the harbinger of a brain metastatic sellar/suprasellar mass. The case highlights the importance of prompt neuroimaging in isolated cranial nerve palsies, particularly in younger patients, and consideration of rare aggressive metastasis to the sellar region, where prompt surgery and pathology are critical in identifying the primary carcinoma and to instituting expedited therapy.


Identifying structural and dynamic changes during the Biliverdin Reductase B catalytic cycle.
Biliverdin Reductase B (BLVRB) is an NADPH-dependent reductase that catalyzes the reduction of multiple substrates and is therefore considered a critical cellular redox regulator. In this study, we sought to address whether both structural and dynamics changes occur between different intermediates of the catalytic cycle and whether these were relegated to just the active site or the entirety of the enzyme. Through X-ray crystallography, we determined the apo BLVRB structure for the first time, revealing subtle global changes compared to the holo structure and identifying the loss of a critical hydrogen bond that "clamps" the R78-loop over the coenzyme. Amide and Cα chemical shift perturbations were used to identify environmental and secondary structural changes between intermediates, with more distant global changes observed upon coenzyme binding compared to substrate interactions. NMR relaxation rate measurements provided insights into the dynamic behavior of BLVRB during the catalytic cycle. Specifically, the inherently dynamic R78-loop that becomes ordered upon coenzyme binding persists through the catalytic cycle while similar regions experience dynamic exchange. However, the dynamic exchange processes were found to differ through the catalytic cycle with several groups of residues exhibiting similar dynamic responses. Finally, both local and distal structural and dynamic changes occur within BLVRB that are dependent solely on the oxidative state of the coenzyme. Thus, through a comprehensive analysis here, this study revealed structural and dynamic alterations in BLVRB through its catalytic cycle that are not simply relegated to the active site, but instead, are allosterically coupled throughout the enzyme.


Trajectories of Perceived Workplace Age Discrimination and Long-Term Associations With Mental, Self-Rated, and Occupational Health.
This study addresses older employees' trajectories of perceived workplace age discrimination, and the long-term associations among perceived age discrimination and older workers' mental and self-rated health, job satisfaction, and likelihood of working past retirement age. We evaluate the strength and vulnerability integration (SAVI) model. Three waves of data from employed participants were drawn from the Health and Retirement Study (N = 3,957). Latent growth modeling was used to assess relationships between the slopes and the intercepts of the variables, thereby assessing longitudinal and cross-sectional associations. Perceived workplace age discrimination tends to increase with age, although notable variance exists. The initial status of perceived age discrimination relates to the baseline statuses of depression, self-rated health, job satisfaction, and likelihood of working past retirement age in the expected directions. Over time, perceived age discrimination predicts lower job satisfaction and self-rated health, as well as elevated depressive symptoms, but not likelihood of working past retirement age. This study provides empirical support for the SAVI model and uncovers the "wear and tear" effects of perceived workplace age discrimination on older workers' mental and overall health. We deliberate on social policies that may reduce age discrimination, thereby promoting older employees' health and ability to work longer.


[Prospects and possibilities of prophylactic washing of surgical wounds by pulsating spurs of liquid under pressure].
For bathing of surgical wounds as prophylaxis of wound infection, original apparatus which provides running of the liquid into the wound as impulse pulsating liquid spurts under pressure, is proposed. Washing of surgical wounds by pulsating spurs of liquid diminishes primary dissemination 1000 times and does not produce traumatic action on tissues, promotes washing out blood, fibrin and devitalized tissues from the wound which contributed to favourable healing. Prophylactic bathing of surgical wounds was used in clinic during 384 surgical interventions in abdominal cavity, which resulted in decrease of frequency of wound complications more than 5 times and reduction of hospitalization period after surgery.


Cyanobacterial community composition and their functional shifts associated with biocrust succession in the Gurbantunggut Desert.
Cyanobacteria, as key biocrust components, provide a variety of ecosystem functions in drylands. In this study, to identify whether a cyanobacterial community shift is involved in biocrust succession and whether this is linked to altered ecological functions, we investigated cyanobacterial composition, total carbon and nitrogen contents of biocrusts in the Gurbantunggut Desert. Our findings showed that the biocrust cyanobacteria in the Gurbantunggut desert were mostly filamentous, coexisting with abundant unicellular colonial Chroococcidiopsis. Heterocystous Nostoc, Scytonema and Tolypothrix always represented the majority of biocrust nitrogen-fixing organisms, comprising an average of 92% of the nifH gene reads. Community analysis showed a clear shift in prokaryotic community composition associated with biocrust succession from cyanobacteria- to lichen- and moss-dominated biocrusts, and filamentous non-nitrogen-fixing cyanobacteria-dominated communities were gradually replaced by nitrogen-fixing and unicellular colonial communities. Along the succession, there were concomitant reductions in cyanobacterial relative abundance, whereas Chl-a, total carbon and nitrogen contents increased. Concurrently, distinct carbon and nitrogen stores shifts occurred, implying that the main ecological contribution of cyanobacteria in biocrusts changes from carbon- to nitrogen-fixation along with the succession. Our results suggest that any activity that reverses biocrust succession will influence cyanobacterial community composition and eventually lead to large reductions in soil carbon and nitrogen stores.


The economic costs of asthma: a review and conceptual model.
There is a growing international concern about increasing asthma morbidity. While much is known about asthma morbidity, there are few available data on the economic burden of this condition, particularly in underdeveloped countries. In the absence of data on social costs, it is not possible to develop rational approaches to policies regarding resource allocation to reduce morbidity. The purpose of this article is to provide a review of the available literature on the social costs of illness for asthma. In light of this literature, we propose a conceptual model that links asthma morbidity to the social opportunity costs of the disease. We then delineate a framework, based on the proposed model, that can be used to conceptualise and evaluate the relative impact of alternative asthma intervention strategies. Based upon proposed analyses using this model, we believe that it would be possible to compare how various intervention strategies are likely to affect asthma costs and morbidity, thus providing a means for a more rational approach to healthcare policies regarding societal resource allocation for asthma.


Diffuse idiopathic neuroendocrine cell hyperplasia as a rare cause of chronic cough.
A 39-year-old Caucasian woman, who has never smoked, presented a 16-year-duration chronic dry cough. She was prescribed by her general physician with corticosteroid and long-acting β-agonist inhalers assuming it was asthma, with mild symptomatic improvement. When cough got more persistent and associated with exertional dyspnoea and wheezing, a chest CT scan was performed, which showed multiple bilateral micronodular formations and diffuse mosaic lung pattern with air trapping. She was sent to our Respiratory Department and performed a bronchoalveolar lavage and cryobiopsy that were inconclusive. She underwent surgical lung biopsy with pathology revealing multiple foci of neuroendocrine cell hyperplasia and tumourlets associated with constrictive bronchiolitis, a histological pattern suggestive of diffuse idiopathic neuroendocrine cell hyperplasia (DIPNECH). DIPNECH is a rare and preinvasive disease. Presenting symptoms can be cough and breathlessness. At the time of writing, the patient is on octreotide with symptomatic improvement.


A multistage, optimal active contour model.
Energy-minimizing active contour models or snakes can be used in many applications such as edge detection, motion tracking, image matching, computer vision, and three-dimensional (3-D) reconstruction. We present a novel snake that is superior both in accuracy and convergence speed over previous snake algorithms. High performance is achieved by using spline representation and dividing the energy-minimization process into multiple stages. The first stage is designed to optimize the convergence speed in order to allow the snake to quickly approach the minimum-energy state. The second stage is devoted to snake refinement and to local minimization of energy, thereby driving the snake to a quasiminimum-energy state. The third stage uses the Bellman (1957) optimality principle to fine-tune the snake to the global minimum-energy state. This three-stage scheme is optimized for both accuracy and speed.


Prevalence of Escherichia coli O157 and levels of aerobic bacteria and Enterobacteriaceae are reduced when hides are washed and treated with cetylpyridinium chloride at a commercial beef processing plant.
The objective of this experiment was to test the potential of a combined water wash and cetylpyridinium chloride (CPC) treatment as a hide intervention applied to cattle in the holding pens of a processing plant immediately before stunning. Over 2 processing days, 149 control and 139 treated cattle were tested. Control cattle were processed in the normal manner. The treatment group was prewashed with water the day before harvest. Immediately before stunning, these cattle were sprayed twice with 1% CPC, first for 3 min, then for 1 min. Hides and preevisceration carcasses were sampled to determine aerobic plate counts, Enterobacteriaceae counts (EBC), and Escherichia coli O157 prevalence. The treatment reduced the prevalence of E. coli O157 on hides from 56% to 34% and the prevalence on preevisceration carcasses from 23% to 3%. The treatment decreased aerobic plate counts from 4.9 log CFU/100 cm2 to 3.4 log CFU/100 cm2 and EBC from 3.1 log CFU/100 cm2 to 2.0 log CFU/100 cm2 on preevisceration carcasses. The treatment of hides did not result in any detectable CPC contamination of the chilled carcasses. These data indicated that a 1% CPC treatment preceded by a water wash was capable of reducing hide prevalence of E. coli O157 from as high as 80% to less than 50%, resulting in preevisceration carcass prevalence of 5% or less. We conclude that water washing followed by an antimicrobial treatment, such as CPC, has great potential as an effective hide intervention step and should be further evaluated for implementation as a processing step after stunning and before hide removal.


Direct delivery of bacterial avirulence proteins into resistant Arabidopsis protoplasts leads to hypersensitive cell death.
Many bacterial avirulence (Avr) proteins, including the Pseudomonas syringae proteins, AvrRpt2 and AvrB, appear to be recognized inside the host plant cell by resistance mechanisms mediated by the cognate resistance (R) genes. It is thought that Avr proteins are either delivered directly into the host cell via the bacterial type III secretion system (TTSS) or taken up by the plant cell following secretion into the apoplast through the TTSS. Recently, it was shown that the Xanthomonas campestris AvrBs2 protein can be delivered directly into the host plant cell by the TTSS. However, it is not known whether other type III effectors of phytopathogens behave similarly. Here, using a novel protein transfection method, we demonstrate that AvrRpt2 and AvrB must enter the plant cell to be recognized by R gene-mediated mechanisms. First, we established a hypersensitive cell death assay for protoplasts using the membrane-impermeable, nuclear-staining dye, YO-PRO-1, and transgenic Arabidopsis plants that carry an inducible avrRpt2 gene. Second, we transfected E. coli-produced AvrRpt2 or AvrB proteins into Arabidopsis protoplasts using a protein transfection kit based on the carrier peptide Pep-1, and demonstrated that hypersensitive cell death occurs in a gene-for-gene-specific manner. In contrast, these Avr proteins failed to elicit hypersensitive cell death when they were applied to protoplasts without the carrier peptide. We conclude that our preparations of E. coli-produced AvrRpt2 and AvrB are active, that AvrRpt2 and AvrB must be delivered into the plant cell to be recognized, and that a method based on a carrier peptide can be used to introduce proteins into plant cells.


Combined hepatocellular cholangiocarcinoma in hepatectomy specimens: A clinicopathologic analysis.
Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is an uncommon form of primary liver carcinoma. It is heterogenous in terms of morphology, immunohistochemistry, radiology, and clinical features; making it a challenging entity for diagnosis. The purpose of the present study was to evaluate clinicopathological characteristics of patients with cHCC-CCA. Retrospective observational study. The patients diagnosed with cHCC-CC were identified from hepatic surgical specimens and were evaluated. Survival was estimated as per Kaplan-Meier method. Out of six patients, five had undergone resection while one had liver transplant. Five were male and one was female and the mean age was 52 years. Tumor markers revealed raised serum alfa-fetoprotein and CA19.9 in four and three patients, respectively. Five of the liver specimens were cirrhotic. Diagnosis was predominantly based on tumor morphology. All cases were of Allen and Lisa type B and cHCC-CCA as per WHO (2019) classification. Stem cell features <5% were noted in two cases. Immunohistochemistry for programmed death 1/programmed death ligand 1 (PD1/PDL1) was negative in both the hepatocellular and cholangiocellular components in all six cases. Mismatch repair (MMR) protein expression was retained in two and deficient in four cases. The median follow-up after surgery was 21.3 months (range, 5-46.2 months). Five patients had intrahepatic and/or extrahepatic recurrence on follow-up after surgery. The median recurrence-free survival was estimated at 13.1 months (95% CI 5.67-20.6). Three patients had received salvage treatment. The median overall survival was estimated at 20 months (95% CI 0-45.3). The present study highlights the role of morphology in the diagnosis of cHCC-CCA. The choice of locoregional and/or systemic therapy after surgery may be individualized based on the clinicopathological characteristics.


On the origin, homologies and evolution of primate facial muscles, with a particular focus on hominoids and a suggested unifying nomenclature for the facial muscles of the Mammalia.
The mammalian facial muscles are a subgroup of hyoid muscles (i.e. muscles innervated by cranial nerve VII). They are usually attached to freely movable skin and are responsible for facial expressions. In this study we provide an account of the origin, homologies and evolution of the primate facial muscles, based on dissections of various primate and non-primate taxa and a review of the literature. We provide data not previously reported, including photographs showing in detail the facial muscles of primates such as gibbons and orangutans. We show that the facial muscles usually present in strepsirhines are basically the same muscles that are present in non-primate mammals such as tree-shrews. The exceptions are that strepsirhines often have a muscle that is usually not differentiated in tree-shrews, the depressor supercilii, and lack two muscles that are usually differentiated in these mammals, the zygomatico-orbicularis and sphincter colli superficialis. Monkeys such as macaques usually lack two muscles that are often present in strepsirhines, the sphincter colli profundus and mandibulo-auricularis, but have some muscles that are usually absent as distinct structures in non-anthropoid primates, e.g. the levator labii superioris alaeque nasi, levator labii superioris, nasalis, depressor septi nasi, depressor anguli oris and depressor labii inferioris. In turn, macaques typically lack a risorius, auricularis anterior and temporoparietalis, which are found in hominoids such as humans, but have muscles that are usually not differentiated in members of some hominoid taxa, e.g. the platysma cervicale (usually not differentiated in orangutans, panins and humans) and auricularis posterior (usually not differentiated in orangutans). Based on our observations, comparisons and review of the literature, we propose a unifying, coherent nomenclature for the facial muscles of the Mammalia as a whole and provide a list of more than 300 synonyms that have been used in the literature to designate the facial muscles of primates and other mammals. A main advantage of this nomenclature is that it combines, and thus creates a bridge between, those names used by human anatomists and the names often employed in the literature dealing with non-human primates and non-primate mammals.


Muscle-Inspired Highly Anisotropic, Strong, Ion-Conductive Hydrogels.
Biological tissues generally exhibit excellent anisotropic mechanical properties owing to their well-developed microstructures. Inspired by the aligned structure in muscles, a highly anisotropic, strong, and conductive wood hydrogel is developed by fully utilizing the high-tensile strength of natural wood, and the flexibility and high-water content of hydrogels. The wood hydrogel exhibits a high-tensile strength of 36 MPa along the longitudinal direction due to the strong bonding and cross-linking between the aligned cellulose nanofibers (CNFs) in wood and the polyacrylamide (PAM) polymer. The wood hydrogel is 5 times and 500 times stronger than the bacterial cellulose hydrogels (7.2 MPa) and the unmodified PAM hydrogel (0.072 MPa), respectively, representing one of the strongest hydrogels ever reported. Due to the negatively charged aligned CNF, the wood hydrogel is also an excellent nanofluidic conduit with an ionic conductivity of up to 5 × 10-4 S cm-1 at low concentrations for highly selective ion transport, akin to biological muscle tissue. The work offers a promising strategy to fabricate a wide variety of strong, anisotropic, flexible, and ionically conductive wood-based hydrogels for potential biomaterials and nanofluidic applications.


Family physicians' quality interventions and performance improvement through the ABFM diabetes performance in practice module.
Practice performance assessment is the fourth requirement of Maintenance of Certification for Family Physicians (MC-FP). American Board of Family Medicine (ABFM) diplomates have many options for completing Part 4 requirements, including Web-based Performance in Practice Modules (PPMs) developed by the ABFM. Our objective was to describe the actions and outcomes of family physicians who completed the ABFM diabetes PPM. We undertook a descriptive study of all diabetes PPMs completed by physicians in the 50 United States and Washington, DC, from 2005 to October 2012. Successful completion required quality measure abstraction from 10 patient charts before and after a plan-do-study-act cycle improvement effort. We used descriptive statistics to assess physician demographics and quality outcomes. Family physicians completed 7,924 diabetes qualitative improvement modules. Their mean age was 48.2 years, they had practiced a mean of 13.8 years, and three-fourths lived in urban areas (76.9%). Nearly one-half selected diabetic foot examination or eye examination as their quality improvement measure. Performance on all quality measures improved. Significant improvement was seen in rates of hemoglobin A1c control (<7.0%; 57.4% to 61.3%), blood pressure control (<130/90 mm Hg; 53.3% to 56.3%), foot examinations (68.0% to 85.8%); and retina examinations (55.5% to 71.1%). The most common interventions were standing orders (51.6%) and patient education (37.1%). Family physicians participating in MC-FP implemented improvement projects and showed quality improvements in caring for patients with diabetes. Emphasis on quality of care by payers will increasingly require physicians to embrace quality measurement and improvement.


Artificial light-harvesting n-type porphyrin for panchromatic organic photovoltaic devices.
A near-infrared-harvesting n-type porphyrin-based acceptor for organic photovoltaics (OPVs) was developed. The n-type acceptor, PDI-PZn-PDI, was designed by connecting a zinc porphyrin (PZn) core to two perylenediimide (PDI) wings through ethyne bridges. A narrow bandgap of 1.27 eV was achieved through the extended π-conjugation and intramolecular charge transfer between the strongly electron-donating PZn core and the electron-accepting PDI wings. A bulk heterojunction (BHJ) structured photovoltaic device fabricated from PDI-PZn-PDI with PTB7-Th exhibited panchromatic photon-to-current conversion from 350 to 900 nm. A power conversion efficiency of 5.25% with a remarkably low Eloss of 0.54 eV was achieved by optimizing the nanomorphology of the BHJ films by adding pyridine and by controlling the ZnO/BHJ interfacial properties.


Vaccinia virus protein C4 inhibits NF-κB activation and promotes virus virulence.
Vaccinia virus (VACV) strain Western Reserve protein C4 has been characterized and its function and contribution to virus virulence assessed. Bioinformatic analysis showed that C4 is conserved in six orthopoxvirus species and shares 43 % amino acid identity with VACV protein C16, a known virulence factor. A recombinant VACV expressing a C-terminally tagged version of C4 showed that, like C16, this 37 kDa protein is expressed early during infection and localizes to both the cytoplasm and the nucleus. Functional assays using a firefly luciferase reporter plasmid under the control of a nuclear factor kappa B (NF-κB)-dependent promoter demonstrated that C4 inhibits NF-κB activation at, or downstream of, the inhibitor of kappa kinase (IKK) complex. Consistent with this, C4 inhibited interleukin-1β-induced translocation of p65 into the nucleus. A VACV lacking the C4L gene (vΔC4) showed no significant differences from wild-type virus in growth kinetics or spread in cell culture, but had reduced virulence in a murine intranasal model of infection. vΔC4-infected mice exhibited fewer symptoms, lost less weight and recovered 7 days earlier than animals infected with control viruses expressing C4. Furthermore, bronchoalveolar lavage fluid from vΔC4-infected mice had increased cell numbers at day 5 post-infection, which correlated with reduced lung virus titres from this time onward. C4 represents the ninth VACV protein to inhibit NF-κB activation and remarkably, in every case examined, loss of each protein individually caused an alteration in virus virulence, despite the presence of other NF-κB inhibitors.


Occasion setting during a spatial-search task with pigeons.
A spatial task was used to investigate if a stimulus could set the occasion for responding to a landmark. Pigeons were trained with a positive occasion setter (OS; a colored background display) signaling the contingency between a landmark (LM; visual patterned stimulus) and the location of a rewarded response. The two most common tests of an OS (transfer tests and post-training extinction of the OS) were then conducted. In Experiment 1, two occasion setting pairs were trained (+←XA/YB→+/A-/B-) with unique spatial relationships to a reinforced goal location. Transfer tests (XB- and YA-) revealed more responding to a landmark when paired with the same OS from training (e.g., XA) than on transfer tests, which was greater still than landmark-only trials (A-). Three pigeons demonstrated good spatial control of responding by the LM on transfer tests. In Experiment 2, the contingency and spatial relationship (e.g., left or right) between LM A and the goal were signaled by the OS (+←XA/YA→+/+←ZB/C→+/A-/B-). LM C was trained without an OS to assess the role of training history during transfer. Transfer tests again indicated an OS could facilitate responding and the LM controlled the location of responding. Training history affected spatial control, but not facilitation, by LM C. Lastly, post-training extinction of X had no effect on facilitation or spatial control during subsequent XA trials. These experiments are the first to evaluate conditional control of spatial information by landmarks using both of the standard tests for occasion setting.


Effect of cutaneous stimulation on pain reduction in emergency department patients.
The problem of unrelieved pain in Emergency Department (ED) patients as well as contraindications to analgesics and narcotics due to masking of symptoms during the diagnostic period, presents itself as a unique opportunity for ED nurses to utilize non-pharmacological and non-invasive interventions such as cutaneous stimulation (CS) to relieve pain. To evaluate the effectiveness of a specific protocol of CS, developed by the researchers, in reducing pain levels in ED patients. Another objective was to determine the effect of CS on blood pressure and heart rate. Potential factors that could influence the dependent variables such as age, gender, educational level, location of pain, and site of CS were tested. A one group pre-test post-test experimental design measured variables before and after intervention in all subjects. After being screened for inclusion, 50 patients (38 adults, 12 children) were admitted to the study and were treated with CS to relieve pain. Following CS, subjects reported significantly reduced pain, and demonstrated reduced heart rate, and blood pressure readings. The location of pain significancy influenced heart rate and diastolic blood pressure but not pain level. The most effective site of CS was contralateral to the pain. Age, gender and educational level had no significant affect. The results of this study provide empirical evidence that CS effectively reduces pain, heart rate, and blood pressure in ED patients. The intervention of CS has solid utilization potential and could be easily incorporated into standard ED procedure. Further research is needed to identify threats to internal validity especially that of the caring presence of the nurse.


Effects of an organophosphate pesticide, quinalphos, on the hypothalamo-pituitary-gonadal axis in adult male rats.
The effects of chronic sub-lethal doses (7-14 mg kg-1 a day for 15 days) of quinalphos were evaluated in adult male rats for changes in testicular morphology, circulatory concentrations of hormones (LH, FSH, prolactin and testosterone), activities of acetylcholinesterase (AChE) and angiotensin converting enzyme (ACE) as well as metabolism of biogenic amines (dopamine, noradrenaline and 5-hydroxytryptamine (5-HT)) in the hypothalamus and pituitary. Hormones were assayed by radioimmunoassay or chemiluminescent immunoassay (testosterone). The enzymes were estimated after spectrophotometry and the biogenic amines by HPLC-electrochemistry. Sub-lethal chronic administration of quinalphos resulted in: decreased testicular mass and AChE activity in central as well as peripheral organs; increased serum LH, FSH, prolactin and testosterone concentrations; decreased pituitary or increased testicular ACE activity; severe disruption of spermatogenesis with increasing doses of pesticide; and no significant effects on dopamine, noradrenaline or 5-HT concentrations in the hypothalamus or pituitary. Administration of oestradiol (50 micrograms per rat a day) during pesticide treatment resulted in: a significant decrease in the mass of the testis and accessory sex organs; decreases in serum LH, FSH, testosterone concentrations; an increase in prolactin concentration; and a decrease in dopamine or an increase in noradrenaline and 5-HT in the hypothalamus or pituitary. Oestradiol had a marked effect: in pesticide-treated animals, the pesticide effects were significantly reversed. This indicates that in pesticide toxicity, the hypothalamo-pituitary-gonadal axis is operational. Since many of the observed pesticide effects could be inhibited by oestradiol, it is suggested that the pesticide acts directly on the gonadotrophins. In conclusion, quinalphos decreases fertility in adult male rats by affecting the pituitary gonadotrophins.


A changing culture in interpersonal and communication skills.
In summary it is essential that we improve our interpersonal and communication skills. We can learn and be taught better skills. We will be evaluated on these skills in the future, and it is important for us to establish ourselves as good role models for the future surgeons who will be entering our profession. It is of benefit to our patients and will give them a better understanding of their disease and elevate their level of healthcare. It is also important to us to help reduce our stress and to eliminate burnout. We can improve our interpersonal and communication skills in many ways. First we must be aware that there is a problem and recognize this as a problem that can be solved and that we do need to improve our current skills. This can be done through multiple educational tools such as lectures, videos, and self-assessments. The responsibility for this culture change ranges from top to bottom, but really begins at the bottom. It is important for all of us especially individuals such as myself, who is not only a practicing surgeon but also a surgeon in a leadership position, a surgeon who teaches medical students and residents, and a chairman who develops the careers of young faculty members. It is important for organizations such as the Southeastern Surgical Congress to recognize this need of our members and to conduct seminars, luncheons, and courses in helping us acquire better skills and also giving us some assessment of the current status of our skills. The American College of Surgeons has already addressed this issue by forming the Task Force on Communication and Educational Skills. Various examining boards have already incorporated this into requirements and expectations of future physicians and surgeons. We must establish ourselves as good role models. Being a good role model cannot be overemphasized. We are very fortunate in being good role models in medical knowledge and mastering phenomenal technical feats; however, this is not enough. It is also important that we also improve our interpersonal and communication skills. We must establish goals and outcomes for ourselves and work on ways of assessing these to ensure that we are effective in improving our skills. We must incorporate interpersonal and communication skills into our training programs, postgraduate courses, and all aspects of lifelong continuing education. Addressing the improvement of our interpersonal and communication skills will have many beneficial effects including improved patient outcomes, a better healthcare status for our patients, and a high level of confidence that patients have in us as physicians and surgeons. We do at times have a less than ideal collegial relationship with other disciplines in medicine. This faulty relationship needs to be rectified. We need to restore and maintain a high collegial relationship with everyone in medicine not only other physicians, but also nurses, paramedical personnel, and others. These changes will require a great deal of effort and will take some considerable time. Initially laparoscopic cholecystectomy and laparoscopic skills were not adequately learned but with recognition of its importance, education, and time, we became master surgeons. We are very fortunate to have residents and practitioners with superb laparoscopic skills that they acquired during their training and in structured postgraduate courses. Likewise it is important to incorporate interpersonal and communication skills into our training programs and our continuing medical educational programs. Finally, this is not just a touchy-feely issue, but it is one of surgical professionalism. It is critical for us to address this as an important issue since it will enhance the good qualities that we already possess. Let's start today. I have enjoyed this year being your President, and wish to thank you for the opportunity of addressing you this morning.


Endocrine treatment of aging transgender people.
High quality empirical data assessing morbidity and mortality and cancer incidence among transgender people are almost non-existent. Sex hormone treatment of conditions in older non-transgender people might as yet be taken as the best available analogy to hormone administration to aging transgender persons. Testosterone administration to transgender men carries little risk with regard to cardiovascular disease and cancer. A dose adaptation may be needed in men with a high hematocrit or cardiac insufficiency. In transgender men, even after breast ablation, breast cancer may occur in residual mammary tissue. Treatment with estrogens (specifically oral ethinylestradiol) of transgender women, particularly in combination with progestins, carries a significant relative risk of developing cardiovascular disease (almost a twofold incidence compared to the general population). The dose of estrogens may have to be reduced with aging. A change from oral to probably safer transdermal estrogens must be considered. Though rare, tumors of the breasts, prostate, meninges and pituitary have been encountered. Based upon the available expertise, initiation of cross-sex hormone treatment in elderly subjects is without disproportionate risks.


Multi-photon excitation of intrinsic protein fluorescence and its application to pharmaceutical drug screening.
The majority of proteins contain intrinsic fluorophores as natural sensors of molecular structures, dynamics, and interactions. The intrinsic protein fluorescence signal allows for the label-free and, hence, undisturbed and rapid study of protein-ligand interactions. Ultraviolet-based drug screening is hampered by the background, photobleaching, light scattering, inner filter effects, and interfering assay compounds. Such problems can be overcome by means of molecular three-photon excitation (3PE) with infrared femtosecond light pulses since longer excitation wavelengths result in less Raleigh scattering, and the subfemtoliter (confocal-like) 3PE volume minimizes out-of-focus photobleaching, background generation, and inner filter effects. We demonstrate the general feasibility of 3PE for protein spectroscopy and illustrate the technique's excellent potential for high-throughput screening. By using the intrinsic fluorescence intensity of a protein-substrate, we were able to discriminate between ligands of different affinities in binding assays.


In vivo mitotic spindle scaling can be modulated by changing the levels of a single protein: the microtubule polymerase XMAP215.
In many organisms, early embryonic development is characterized by a series of reductive cell divisions that result in rapid increases in cell number and concomitant decreases in cell size. Intracellular organelles, such as the nucleus and mitotic spindle, also become progressively smaller during this developmental window, but the molecular and mechanistic underpinnings of these scaling relationships are not fully understood. For the mitotic spindle, changes in cytoplasmic volume are sufficient to account for size scaling during early development in certain organisms. This observation is consistent with models that evoke a limiting component, whereby the smaller absolute number of spindle components in smaller cells limits spindle size. Here we investigate the role of a candidate factor for developmental spindle scaling, the microtubule polymerase XMAP215. Microinjection of additional XMAP215 protein into Xenopus laevis embryos was sufficient to induce the assembly of larger spindles during developmental stages 6.5, 7, and 8, whereas addition of a polymerase-incompetent XMAP215 mutant resulted in a downward shift in the in vivo spindle scaling curve. In sum, these results indicate that even small cells are able to produce larger spindles if microtubule growth rates are increased and suggest that structural components are not limiting.


The Not Underrepresented Minorities: Asian Americans, Diversity, and Admissions.
Several lawsuits have recently been filed against U.S. universities; the plaintiffs contend that considerations of race and ethnicity in admissions decisions discriminate against Asian Americans. In prior cases brought by non-Latino whites, the U.S. Supreme Court has upheld these considerations, arguing that they are crucial to a compelling interest to increase diversity. The dissenting opinion, however, concerns the possibility that such policies disadvantage Asian Americans, who are considered overrepresented in higher education. Here, the authors explain how a decision favoring the plaintiffs would affect U.S. medical schools. First, eliminating race and ethnicity in holistic review would undermine efforts to diversify the physician workforce. Second, the restrictions on considering race/ethnicity in admissions decisions would not remedy potential discrimination against Asian Americans that arise from implicit biases. Third, such restrictions would exacerbate the difficulty of addressing the diversity of experiences within Asian American subgroups, including recognizing those who are underrepresented in medicine. The authors propose that medical schools engage Asian Americans in diversity and inclusion efforts and recommend the following strategies: incorporate health equity into the institutional mission and admissions policies, disaggregate data to identify underrepresented Asian subgroups, include Asian Americans in diversity committees and support faculty who make diversity work part of their academic portfolio, and enhance the Asian American faculty pipeline through support and mentorship of students. Asian Americans will soon comprise one-fifth of the U.S. physician workforce and should be welcomed as part of the solution to advancing diversity and inclusion in medicine, not cast as the problem.


Economic modeling of the use of gonadotropin-releasing hormone at insemination to improve fertility in dairy cows.
Economic and sensitivity analysis methods were used to evaluate financial returns from use of gonadotropin-releasing hormone (GnRH) at the time of insemination to enhance fertility of dairy cows. A computer spread sheet was used to determine the best service(s) for GnRH treatment, the increase in conception rate required for economic benefit from treatment, and how profits from GnRH treatment are affected by drug cost, herd reproductive efficiency, and production costs. Financial returns increased from use of GnRH at insemination under most herd conditions. Herds with conception rates less than or equal to 45% benefited from GnRH treatment at any 1 or 2 inseminations. Herds with conception rates greater than or equal to 60% benefited from GnRH treatment only at second or later services. Selection of second and/or third insemination as the GnRH treatment service usually resulted in the greatest total return. The enhancement of fertility necessary to achieve the break-even point with GnRH treatment at third service was 2% for low- and 5% for high-conception-rate herds. Base-line herd conception rates, estrus detection efficiency, replacement costs, value of excess days not pregnant, and cost of treatment had the greatest effect on returns from treatment. Herds with high conception rates and low replacement costs were likely to realize the least benefit from GnRH treatment at insemination. On the basis of our findings, we concluded that GnRH treatment at insemination is a profitable procedure under most herd conditions. Optimal treatment regimens for specific herds may best be determined by using herd performance and management data for calculating returns.


HIV-Infected Women Gain More Weight than HIV-Infected Men Following the Initiation of Antiretroviral Therapy.
Obesity is prevalent among HIV-infected individuals on antiretroviral therapy (ART). Cross-sectional studies have suggested that HIV-infected women are more likely to be overweight than men, but observational studies evaluating sex differences in body mass index (BMI) increases following ART initiation are conflicting. We pooled data from three randomized clinical trials of ART initiation in persons with HIV in the United States. BMIs were compared between 760 women and 3041 men to test whether BMI changes in the first 96 weeks following initiation of ART differed by sex at birth. Linear regression estimated the relationship between sex and change in BMI from pre-ART initiation to week 96. After 96 weeks, women gained an average of 1.91 kg/m2 (95% confidence interval [CI] 1.64-2.19), men gained an average of 1.39 kg/m2 (95% CI 1.30-1.48); p for sex difference <0.001; the sex difference persisted within each pre-ART initiation BMI subgroup. After adjusting for pre-ART initiation age, CD4+ count, HIV-1 viral load, race/ethnicity, study, and ART regimen, mean BMI change for women was 0.59 kg/m2 (95% CI 0.37-0.81) more than for men (p < 0.001). Statistical interactions were observed between sex and both pre-ART CD4+ count and HIV-1 viral load and suggest that for subgroups with higher viral load and lower CD4+ at baseline, the estimated BMI changes in women are even larger than the average estimated difference. HIV-1-infected women experienced a significantly greater increase in BMI following ART initiation than men. These differences are a problem of clinical significance to women living with HIV.


A novel approach to improve health status measurement in observational claims-based studies of cancer treatment and outcomes.
To develop and provide initial validation for amultivariate, claims-based prediction model for disability status (DS), a proxymeasure of performance status (PS), among older adults. The model was designed to augment information on health status at the point of cancer diagnosis in studies using insurance claims to examine cancer treatment and outcomes. We used data from the 2001–2005 Medicare Current Beneficiary Survey (MCBS), with observations randomly split into estimation and validation subsamples. We developed an algorithm linking self-reported functional status measures to a DS scale, a proxy for the Eastern Cooperative Oncology Group (ECOG) PS scale. The DS measure was dichotomized to focus on good [ECOG 0–2] versus poor [ECOG 3–4] PS. We identified potential claims-based predictors, and estimated multivariate logistic regression models, with poor DS as the dependent measure, using a stepwise approach to select the optimal model. Construct validity was tested by determining whether the predicted DS measure generated by the model was a significant predictor of survival within a validation sample from the MCBS. One-tenth of the beneficiaries met the definition for poor DS. The base model yielded high sensitivity (0.79) and specificity (0.92); positive predictive value=48.3% and negative predictive value=97.8%, c-statistic=0.92 and good model calibration. Adjusted poor claims-based DS was associated with an increased hazard of death (HR=3.53, 95% CI 3.18, 3.92). The ability to assess DS should improve covariate control and reduce indication bias in observational studies of cancer treatment and outcomes based on insurance claims.


Oesophageal mucosal blood flow changes after thoracic endovascular stent graft implantation using a novel sensor probe.
Secondary aorto-oesophageal fistula is a rare, lethal complication occurring after thoracic endovascular aneurysmal repair. The cause of secondary aorto-oesophageal fistula is unknown, but a reduction in local oesophageal mucosal blood flow (OMBF) may be a basis for such a devastating sequela. Our study aims to develop a novel blood flow sensor probe to detect changes in OMBF after thoracic stent graft implantation in an experimental swine model. A novel laser Doppler flowmetry sensor probe incorporating an optical fibre sensor within a nasogastric tube was developed using microelectromechanical system technology. OMBF was measured at various levels using this sensor probe, to test its feasibility before and after thoracic endovascular stent graft implantation covering Th4-Th8 vertebral levels in 6 swine. In the middle oesophagus (Th5-Th7), where the aorta was covered with a stent graft, the measured OMBFs were significantly decreased after thoracic endovascular stent graft implantation than those of baseline (8.6 ± 2.7 vs 18.4 ± 7.9 ml/min/100 g, P < 0.0001), followed by a plateau period for at least 2 h after stent grafting (8.7 ± 3.3 ml/min/100 g, P < 0.0001 vs baseline). OMBFs in the upper (Th1-Th3) and lower (Th9-Th11) oesophagus, where the aorta was not covered with a stent graft, were unaffected by thoracic endovascular stent grafting. The novel laser Doppler flowmetry sensor probe was useful to monitor precise changes of OMBF in a swine model, demonstrating a significant reduction in OMBF after thoracic endovascular stent graft implantation.


[Calculating lifetime risk of CVD and potential health benefits in young adults: a tricky business].
Ten-year risk estimates for cardiovascular disease (CVD) in younger adults (< 45 years old) are generally below thresholds for drug treatment, even in the presence of multiple risk factors. For this population group, European guidelines recommend using lifetime risk (LTR), which predicts the cumulative risk of CVD over the life span. LTR may prompt interventions long before conventional treatment thresholds are reached. LTR estimates were recently adjusted to take into account the potential impacts of therapeutic effects in order to quantify the potential number of CVD-free life years gained. However, assumptions on life-long risk exposure and achievable risk reduction lack evidence beyond what is observed in clinical trials. Furthermore, LTR thresholds above which interventions in young adults are cost effective are currently not known. Therefore, although LTR can be useful for raising awareness and stimulating healthy lifestyles, further research is warranted before it can be recommended for clinical use.


Migrations of young spotted seals (Phoca largha) from Peter the Great Bay, Sea of Japan/East Sea, and the pattern of their use of seasonal habitats.
We studied the migrations of young spotted seals during their annual cycle. In May 2017, we attached satellite tags (SPOT-293A) to three individuals (two underyearlings and one yearling) captured at their breeding ground in Peter the Great Bay, western Sea of Japan/East Sea. The operational time of the installed tags ranged from 207 to 333 days; a total of 27195 locations were uploaded. All three seals migrated east and further north along the coast of the mainland. The average daily migration speed of the seals ranged between 70 and 135 km/day. The yearling moved faster than the underyearlings. During early August, they arrived at their summer habitats, which were located in the northern part of the Tatar Strait (Sea of Japan/East Sea) for the underyearling seals and in Aniva Bay (Sea of Okhotsk) for the yearling seal. While moving from the place of tagging to the summer feeding grounds, the seals covered a distance of 2300 to 3100 km. From August to October, each seal permanently stayed within the same isolated area. The reverse migration of all three seals began in November. When the seals traveled south, they used the same routes by which they had moved north in the spring, but they moved at a faster speed. By December, two seals returned to their natal islands, where both stayed until their transmitters stopped sending signals (in March 2018).


Tracheotomy versus endotracheal intubation for airway management in deep neck space infections.
The aim of the present study was to compare costs and outcomes for patients with deep neck infections who were treated with either tracheotomy or endotracheal intubation. The charts of 85 patients with deep neck space infections were retrospectively studied. Requirements for inclusion in the study were incision and drainage in the operating room, involvement of more than 1 deep anatomic space, impending airway compromise, and maintenance of a postoperative artificial airway. The 85 patients were divided into 2 groups based on the type of airway used for treatment. Group 1 (n = 34) included patients who received a tracheotomy, and group 2 (n = 51) included patients whose airways were maintained with endotracheal intubation until the swelling had resolved sufficiently for extubation. Patients in group 1 had a shorter overall hospital stay (4.8 vs 5.9 days, NS) and spent less time in the intensive care unit (1.1 vs 3.1 days, P <.05). The overall incidence of complications was 6% for group 1 and 10% for group 2. The rate of complications secondary to loss of airway was 3% for group 1 and 6% for group 2. Average costs associated with intensive care resources were 5 times greater and overall hospital stay costs were 60% greater for group 2. Although both methods of airway control are useful and have a unique set of complications, the use of tracheotomy allowed earlier movement to a noncritical care unit and was associated with fewer intensive care costs and less overall cost of hospitalization. Tracheotomy may therefore provide better utilization of critical care resources in this group of patients.


[Diagnostic and prognostic value of electrophysiologic studies in patients with peripheral paralysis of the facial nerve].
An analysis of the period and degree of restitution of the functions of mimical muscles in peripheral paralysis of the facial nerve depending upon changes of the motor and reflectory responses of the orbicular muscle of the eye, the type of changes in the main curves of electroexcitation and the development of all these changes during the first 3 weeks of the disease served as a basis for the determination of an early diagnosis and the level of facial nerve lesions. The study revealed an increase of the latent period of motor and reflex responses of the orbicular eye muscles testifies to disturbances of the myeline structures of the facial nerve. The authors suggest that a low electroexcitability of the stem of the facial nerve is associated not so much with the axonal degeneration, as with the process of demyelinization.


Resting CD4+ T lymphocytes but not thymocytes provide a latent viral reservoir in a simian immunodeficiency virus-Macaca nemestrina model of human immunodeficiency virus type 1-infected patients on highly active antiretroviral therapy.
Despite suppression of viremia in patients on highly active antiretroviral therapy (HAART), human immunodeficiency virus type 1 persists in a latent reservoir in the resting memory CD4(+) T lymphocytes and possibly in other reservoirs. To better understand the mechanisms of viral persistence, we established a simian immunodeficiency virus (SIV)-macaque model to mimic the clinical situation of patients on suppressive HAART and developed assays to detect latently infected cells in the SIV-macaque system. In this model, treatment of SIV-infected pig-tailed macaques (Macaca nemestrina) with the combination of 9-R-(2-phosphonomethoxypropyl)adenine (PMPA; tenofovir) and beta-2',3'-dideoxy-3'-thia-5-fluorocytidine (FTC) suppressed the levels of plasma virus to below the limit of detection (100 copies of viral RNA per ml). In treated animals, levels of viremia remained close to or below the limit of detection for up to 6 months except for an isolated "blip" of detectable viremia in each animal. Latent virus was measured in blood, spleen, lymph nodes, and thymus by several different methods. Replication-competent virus was recovered after activation of a 99.5% pure population of resting CD4(+) T lymphocytes from a lymph node of a treated animal. Integrated SIV DNA was detected in resting CD4(+) T cells from spleen, peripheral blood, and various lymph nodes including those draining the gut, the head, and the limbs. In contrast to the wide distribution of latently infected cells in peripheral lymphoid tissues, neither replication-competent virus nor integrated SIV DNA was detected in thymocytes, suggesting that thymocytes are not a major reservoir for virus in pig-tailed macaques. The results provide the first evidence for a latent viral reservoir for SIV in macaques and the most extensive survey of the distribution of latently infected cells in the host.