[Analysis of Clostridium difficile associated diarrhea in pediatric patients with antibiotic-associated diarrhea].
To analyze the incidence and treatment of Clostridium difficile infection (CDI) in pediatric patients with antibiotic-associated diarrhea (AAD). Clinical data of totally 577 pediatric patients with AAD seen from January 2012 to January 2014 were collected; those children were divided according to age into 4 groups, 0.25 -1 year, >1 -4 years, >4 -12 years and >12 -18 years old groups, and 220 healthy children were enrolled as controls. CDI was tested by C. Diff Quik Chek Complete (QCC) and BD GeneOhm™ C. Diff Assay (BD-PCR) in all children, and the CDI incidence of four groups was added up. All pediatric patients with AAD were divided into mild, general and severe type according to different symptoms of diarrhea, and grading treatment, the general type and severe type of CDI children were treated with metronidazole and (or) vancomycin, afterwards, the results of grading treatment were analyzed. The number of pediatric patients with AAD were 178, 177, 132 and 90 in 0. 25 - 1 year, > 1 -4 years, > 4 - 12 years and > 12 - 18 years old group, respectively. The positive rate of CDI (22. 0% (39/177)) in > 1 -4 years old AAD patients was very significantly higher compared to the controls (4% (4/91), P < 0. 001), the rate of CDI (21. 2% (28/132)) in > 4 - 12 years old AAD pediatric patients was significantly higher compared to the controls (4% (2/53), P = 0. 004), the rates of CDI in 0. 25 - 1 year and > 12 - 18years old AAD groups were not significantly different from that of the controls (P >0. 05). There were 285 mild type AAD children (no CDI children), 176 general type AAD children (including 47 CDI children), and 116 severe type AAD children (including 81 CDI children). After grading and symptomatic treatment, there were 16 recurrent diarrhea in 128 CDI patients (severe type AAD), and the rest recovered. Two cases were transferred for referral treatment, 2 cases died, and the rest 12 recurrent diarrhea children fully recovered after administration of metronidazole, vancomycin, probiotics and symptomatic treatment. The > 1 -12 years old AAD children had higher CDI rate than healthy children; administration of metronidazole and (or) vancomycin was effective for CD infection.


Application of 18S rDNA Clone Library to Detect Diatom Population Diversity in Dianchi.
Objective To detect the diatom population diversity in Dianchi by constructing a 18S rDNA clone library. Methods DNA from diatoms in 6 water samples of Dianchi was amplified with diatom 18S rDNA specific primer.The 18S rDNA clone library was constructed, and clones were randomly selected for sequence. Sequence alignment was performed by BLAST. The diatom population distribution in Dianchi was analyzed and the phylogenetic tree of diatom 18S rDNA in Dianchi waters was established with the MEGA v7.0.14 software. Results Two hundred and forty clones were sequenced, with 167 diatom sequences obtained, including 11 diatom species such as Stephanodiscus, Diatoma, and Melosira. There were certain differences in diatom population distribution among the 6 samples. Conclusion The population distribution of diatom species in Dianchi shows unique features and the sequence analysis of diatom 18S rDNA has a certain reference value to the inference of forensic drowning sites.


Hepatic neutrophil infiltration in the pathogenesis of alcohol-induced liver injury.
ABSTRACT The histopathologic evidence of the presence of neutrophils within the liver parenchyma is a prominent feature of alcoholic hepatitis in both experimental animals and chronic human alcoholics. However, the precise mechanisms by which neutrophils infiltrate the liver and cause liver injury still remain to be fully elucidated. For neutrophils to infiltrate the liver, they have to undergo systemic activation (priming) by proinflammatory cytokines, chemokines, complement factors, and other biologically active molecules (e.g., platelet-activating factor). Neutrophils accumulated in the hepatic microvasculature (sinusoids and postsinusoidal venules) can extravasate (transmigrate) into the hepatic parenchyma if they receive appropriate signals from previously sensitized or distressed cells. Transmigration can be mediated by a chemokine gradient established toward the hepatic parenchyma and generally involves the interaction between adhesion molecules on neutrophils (beta(2) integrins) and on endothelial cells (intercellular adhesion molecules [ICAM-1]). Following transmigration, neutrophils adhere to sensitized hepatocytes through their beta(2) integrins and ICAM-1 expressed on hepatocytes and mediate killing of hepatocytes mostly by oxidant stress and proteases. These neutrophilic events during chronic alcohol ingestion, based mostly on experiments with rodent models, will be emphasized in this review.


Guanidinium and amide CEST mapping of human brain by high spectral resolution CEST at 3 T.
To extract guanidinium (Guan) and amide CEST on the human brain at 3 T MRI with the high spectral resolution (HSR) CEST combined with the polynomial Lorentzian line-shape fitting (PLOF). Continuous wave (cw) turbo spin-echo (TSE) CEST was implemented to obtain the optimum saturation parameters. Both Guan and amide CEST peaks were extracted and quantified using the PLOF method. The NMR spectra on the egg white phantoms were acquired to reveal the fitting range and the contributions to the amide and GuanCEST. Two types of CEST approaches, including cw gradient- and spin-echo (cwGRASE) and steady state EPI (ssEPI), were implemented to acquire multi-slice HSR-CEST. GuanCEST can be extracted with the PLOF method at 3 T, and the optimum B 1 = 0.6 μ T $$ {\mathrm{B}}_1=0.6\kern0.2em \upmu \mathrm{T} $$ was determined for GuanCEST in white matter (WM) and 1.0 μT in gray matter (GM). The optimum B1 = 0.8-1 μT was found for amideCEST. AmideCEST is lower in both WM and GM collected with ssEPI compared to those by cwGRASE (ssEPI = [1.27-1.63]%; cwGRASE = [2.19-2.25]%). The coefficients of variation (COV) of the amide and Guan CEST in both WM and GM for ssEPI (COV: 28.6-33.4%) are significantly higher than those of cwGRASE (COV: 8.6-18.8%). Completely different WM/GM contrasts for Guan and amide CEST were observed between ssEPI and cwGRASE. The amideCEST was found to have originated from the unstructured amide protons as suggested by the NMR spectrum of the unfolded proteins in egg white. Guan and amide CEST mapping can be achieved by the HSR-CEST at 3 T combing with the PLOF method.


Growth in cerebral palsy.
Cerebral palsy is often accompanied by abnormalities of growth and nutrition; children with severe motor impairments are most at risk. Nutrition, neurological, and endocrine factors all contribute to suboptimal growth. Poor growth and nutrition are associated with poor general health outcomes and reduced levels of participation, and therefore warrant careful evaluation and appropriate intervention. The lack of normative data combined with the complex interaction of nutrition and nonnutrition factors contributing to growth in this population present real difficulties in management. Particular care is needed to avoid overfeeding and the resultant increase in fat mass and associated morbidity.


Construction of Core-Cross-Linked Polymer Micelles with High Biocompatibility and Stability for pH/Reduction Controllable Drug Delivery.
Polymer micelles have been studied extensively in drug delivery systems (DDS), and their stability is well known to directly affect drug delivery. In this article, a series of amphiphilic copolymers LA-PDPAn-PVPm were synthesized to prepare core-cross-linked nanoparticles (CNP) applied to controllable and targeted anticancer drug delivery. The copolymers could self-assemble in aqueous solution and form homogeneous spherical micelles with particle sizes of between 100 and 150 nm. A comparison between un-cross-linked UCNP and CNP showed that the cross-linking of LA could significantly improve the stability and responsive ability of the nanoparticles. From the in vitro-simulated drug release experiments, CNP was found to have great drug blocking ability under normal physiological conditions and could achieve rapid and efficient drug release under acidic/reducing conditions. In addition, cell experiments showed that CNP had superior biocompatibility and could target tumor cells for drug release. In conclusion, a drug carrier based on copolymer LA-PDPA-PVP realized effective controlled drug release due to the cross-linking of LA. The results will provide guidance for the design strategy of polymer micelles for drug carriers.


Intracoronary beta radiation: state of the art.
This state-of-the-art review is intended to explore the development of beta radiation including catheter delivered and permanent implants from its inception to current practice. Specific focus will be given to the isotopes currently available, radiation physics of beta emitters, preclinical studies, clinical trials, beta radiation delivery systems, and implications for future practice. The encouraging results from the clinical trials have established vascular brachytherapy as a standard of care for patients with in-stent restenosis. Vascular brachytherapy requires additional "fine-tuning" to achieve full optimization.


Establishing the shelf life of flexible colonoscopes.
This study was designed to establish a shelf life for processed (peracetic acid) flexible colonoscopes and to demonstrate the adequacy of manual cleaning procedures. The study challenges current practice in Australia where endoscopes are routinely reprocessed prior to use if the endoscope has been sitting at least overnight. The design was a simulated study in the clinical environment and involved artificial contamination of a colonoscope, cleaning validation, and a time series analysis after processing with peracetic acid in a Steris System 1 processor and drying with 100% isopropyl alcohol. The main outcome measure was the presence of bacteria in the internal channels of the colonoscope after cleaning and at 24 and 168 hours after processing with peracetic acid. The findings suggest that colonoscopes may be left for up to 1 week before needing to be reprocessed before use, provided all channels are thoroughly reprocessed and dried, resulting in cost savings and reduced wear and tear on the instruments. The findings also demonstrate the impact of providing feedback to staff on a regular basis about the efficacy of their cleaning techniques.


Abnormal functional resting-state networks in ADHD: graph theory and pattern recognition analysis of fMRI data.
The framework of graph theory provides useful tools for investigating the neural substrates of neuropsychiatric disorders. Graph description measures may be useful as predictor variables in classification procedures. Here, we consider several centrality measures as predictor features in a classification algorithm to identify nodes of resting-state networks containing predictive information that can discriminate between typical developing children and patients with attention-deficit/hyperactivity disorder (ADHD). The prediction was based on a support vector machines classifier. The analyses were performed in a multisite and publicly available resting-state fMRI dataset of healthy children and ADHD patients: the ADHD-200 database. Network centrality measures contained little predictive information for the discrimination between ADHD patients and healthy subjects. However, the classification between inattentive and combined ADHD subtypes was more promising, achieving accuracies higher than 65% (balance between sensitivity and specificity) in some sites. Finally, brain regions were ranked according to the amount of discriminant information and the most relevant were mapped. As hypothesized, we found that brain regions in motor, frontoparietal, and default mode networks contained the most predictive information. We concluded that the functional connectivity estimations are strongly dependent on the sample characteristics. Thus different acquisition protocols and clinical heterogeneity decrease the predictive values of the graph descriptors.


Disrupted functional connectivity of the pain network in fibromyalgia.
To investigate the impact of chronic pain on brain dynamics at rest. Functional connectivity was examined in patients with fibromyalgia (FM) (n = 9) and healthy controls (n = 11) by calculating partial correlations between low-frequency blood oxygen level-dependent fluctuations extracted from 15 brain regions. Patients with FM had more positive and negative correlations within the pain network than healthy controls. Patients with FM displayed enhanced functional connectivity of the anterior cingulate cortex (ACC) with the insula (INS) and basal ganglia (p values between .01 and .05), the secondary somatosensory area with the caudate (CAU) (p = .012), the primary motor cortex with the supplementary motor area (p = .007), the globus pallidus with the amygdala and superior temporal sulcus (both p values < .05), and the medial prefrontal cortex with the posterior cingulate cortex (PCC) and CAU (both p values < .05). Functional connectivity of the ACC with the amygdala and periaqueductal gray (PAG) matter (p values between .001 and .05), the thalamus with the INS and PAG (both p values < .01), the INS with the putamen (p = .038), the PAG with the CAU (p = .038), the secondary somatosensory area with the motor cortex and PCC (both p values < .05), and the PCC with the superior temporal sulcus (p = .002) was also reduced in FM. In addition, significant negative correlations were observed between depression and PAG connectivity strength with the thalamus (r = -0.64, p = .003) and ACC (r = -0.60, p = .004). These findings demonstrate that patients with FM display a substantial imbalance of the connectivity within the pain network during rest, suggesting that chronic pain may also lead to changes in brain activity during internally generated thought processes such as occur at rest.


Cyclobutane based "overbred intermediates" and their exploration in organic synthesis.
"Overbred intermediates" have been used in organic synthesis for a long time, but these intermediates are not categorized as such. This name was given recently in Hoffman's book Elements of Synthesis Planning. These intermediates are very useful to synthesize complex carbocyclic molecules. A number of powerful and efficient strategies have been developed by using overbred intermediates through innovative fragmentative transformations. This review is based on four-member overbred intermediates (cyclobutane based) that have been used in the total synthesis of natural products from 1968 to 2020. In the initial part, we have discussed synthetic methods (photochemical, metal-mediated, and other miscellaneous transformations) for the construction of cyclobutane overbred intermediates. In the later section, we have discussed how the overbred skeleton is cleaved through numerous fragmentation methods to access the desired target structure.


[Spatial variation in riparian soil properties and its response to environmental factors in typical reach of the middle and lower reaches of the Yellow River].
Soil and vegetation are the foundation of maintaining riparian ecosystem services, and their spatial distribution and variations can determine the effects of ecological functions. In the present study, selecting the typical reach of the middle and lower reaches of the Yellow River as the study area, the spatial distributions of riparian soil physicochemical properties and their response to environmental factors were analyzed by employing methods of field investigation, experimental analysis, and redundancy analysis (RDA). The results showed that soil particle was composed significantly of silt in the study area, with the increase of riparian buffer distance, soil bulk density increased initially and then decreased, whereas soil moisture showed the opposite pattern. Changes in total soil phosphorus (TP), available phosphorus (AP), total carbon (TC), total organic carbon (TOC), total nitrogen (TN); ammonium nitrogen (NH₄⁺-N) and nitrate nitrogen (NO₃⁻-N) contents under different riparian buffer distance showed no statistically significant differences. The spatial distribution of soil chemical properties was generally insignificantly different through changes between two vegetation types. Pearson correlation analysis showed that there was close relationship between soil physical and chemical properties, therein, TOC content in the study area was positively and significantly related to TN (P < 0.01), NO₃⁻-N (P < 0.01, and NH₄⁺-N (P < 0.05) contents, respectively. Both the TN and TOC contents were significantly negatively related to sand content (P < 0.01), while was significantly positively related to clay content (P < 0.01), indicating that high sand content cou ld pormote poro9sity and permeability of soil and then accelerate the degradation rate of organic matters in soils. In addition, the results of RDA indicated that TOC and NH₄⁺-N contents increased with increasing the height and coverage of the tree layer. Soil TP and NO₃⁻-N contents increased with increasing the plant diameter at breast height (DBH) of the tree layer and coverage of the herb layer. Meanwhile, with the increase of elevation gradient, the content of soil NH₄⁺-N presented an increasing trend, indicating that soil properties were significantly influenced by the effects of community structure and elevation gradient in the study area.


Transforming growth factor-beta 1 promotes re-elongation of injured axons of cultured rat hippocampal neurons.
Transforming growth factor-beta 1 (TGF-beta 1) is highly expressed in neural tissues following brain injuries. To determine a role of TGF-beta 1 in neural pathologies, axons of cultured rat hippocampal neurons were cut by local irradiation of laser beam, and the effect of TGF-beta 1 on neurite regeneration following axotomy was investigated. The axonal growth was stopped by laser irradiation, but addition of TGF-beta 1 remarkably promoted the axonal re-elongation from the injured site. The effect of TGF-beta 1 was concentration dependent and seen maximally at a concentration of 1 ng/ml. These results suggest that TGF-beta 1 has a capability of promoting axonal regeneration of brain neurons after lesioning.


Base and acid treatment of SWCNT-RNA transparent conductive films.
RNA was used to exfoliate single-walled carbon nanotubes (SWCNTs) in aqueous solution, and the ratio of it was optimized to obtain the best dispersion state. The obtained homogeneous SWCNT solution with small bundle size was used to prepare flexible transparent conductive films by filtration method. Sodium hydroxide treatment combining short-time acid treatment was used to remove the RNA molecules. After treatment, the sheet resistance of the films decreased significantly, while the change on the transmittance was negligible. Besides, the polyethylene terephthalate substrate would not turn brittle through this treatment process. Flexible films with outstanding performance (190 Omega/sq, 85%) and good stability were obtained after treatment. X-ray photoelectron spectroscopy and scanning electron microscope were used to analyze the role of base and acid treatment in detail.


Telehealth Screening for Diabetic Retinopathy: Economic Modeling Reveals Cost Savings.
Introduction: The use of telehealth screening (TS) for diabetic retinopathy (DR) consists of fundus photography in a primary care setting with remote interpretation of images. TS for DR is known to increase screening utilization and reduce vision loss compared with standard in-person conventional diabetic retinal exam (CDRE). Anti-vascular endothelial growth factor intravitreal injections have become standard of care for the treatment of DR, but they are expensive. We investigated whether TS for DR is cost-effective when DR management includes intravitreal injections using national data. Materials and Methods: We compared cost and effectiveness of TS and CDRE using decision-tree analysis and probabilistic sensitivity analysis with Monte Carlo simulation. We considered the disability weight (DW) of vision impairment and 1-year direct medical costs of managing patients based on Medicare allowable rates and clinical trial data. Primary outcomes include incremental costs and incremental effectiveness. Results: The average annual direct cost of eye care was $196 per person for TS and $275 for CDRE. On average, TS saves $78 (28%) compared with CDRE and was cost saving in 88.9% of simulations. The average DW outcome was equivalent in both groups. Discussion: Although this study was limited by a 1-year time horizon, it provides support that TS for DR can reduce costs of DR management despite expensive treatment with anti-VEGF agents. TS for DR is equally effective as CDRE at preserving vision. Conclusions: Annual TS for DR is cost saving and equally effective compared with CDRE given a 1-year time horizon.


Chromatin structural rearrangement during dedifferentiation of protoplasts of Cucumis sativus L.
This paper reports on the structural rearrangement of satellite DNA type I repeats and heterochromatin during the dedifferentiation and cell cycling of mesophyll protoplasts of cucumber (Cucumis sativus). These repeats were localized in the telomeric heterochromatin of cucumber chromosomes and in the chromocenters of interphase nuclei. The dramatic reduction of heterochromatin involves decondensation of subtelomeric repeats in freshly isolated protoplasts; however, there are not a great many remarkable changes in the expression profile. In spite of that, reformation of the chromocenters, occurring 48 h after protoplast isolation, is accompanied by recondensation of satellite DNA type I; however, only partial reassembly of these repeats was revealed. In this study, FISH and a flow cytometry assay show a correlation between the partial chromocenter and the repeats reassembly, and with the reentry of cultivated protoplasts into the cell cycle and first cell division. After that, divided cells displayed a higher variability in the expression profile than did leaves' mesophyll cells and protoplasts.


Successful Nonoperative Treatment of Osteochondritis Dissecans of the Humeral Capitellum in a Young Baseball Player with Advanced Skeletal Maturity.
Osteochondritis dissecans (OCD) of the humeral capitellum presents most typically in adolescent athletes who perform repetitive overhead activities. Earlier studies have demonstrated that conservative treatment of OCD is appropriate for patients with an open capitellar growth plate from the standpoint that spontaneous healing can be expected. A 12-year-old male baseball player with two years of experience with a local team participated in our medical check that included screening for capitellar OCD using ultrasonography. The subject experienced elbow pain when throwing, and ultrasonographic elbow examination indicated OCD of the capitellum, detected as irregularity of the subchondral bone of the capitellum. The initial radiograph, taken with the elbow at 45° of flexion, identified new bone formation in the lateral aspect of the OCD lesion; however the epiphyseal lines of the capitellum and lateral epicondyle were closed. We advised the patient to stop heavy use of the elbow, e.g., throwing and batting, and started conservative treatment in anticipation of spontaneous healing. Physiotherapy focusing on the shoulder girdle, core, and hip and lower limb stretches were performed to resolve general tightness. The OCD lesion had healed completely 12 months after the start of conservative treatment. Conservative treatment for young baseball players might be worth considering if lateral new bone formation within the OCD lesion is detected on radiographic findings, even if the epiphyseal lines of the capitellum and lateral epicondyle are closed.


Pregnancy in women with diabetes--after the CEMACH report, what now?
The second of three studies being undertaken by the Confidential Enquiry into Maternal and Child Health (CEMACH) has recently reported its findings and recommendations. The standards of diabetes and maternal care and the outcomes of 3808 pregnancies in England, Wales and Northern Ireland are described. Pre-pregnancy planning and care before conception is poor. Stillbirth rate (26.8 per thousand) and perinatal mortality (41.8 per thousand) were 4-5 times higher than the background population, and congenital anomaly (41.8 per thousand) double the background rate. Type 2 diabetes now represents 27.3% of pre-gestational diabetes and more often of ethnic minority and deprived background than Type 1 diabetes. The ideals of the Diabetes National Service Framework and the target of the Saint Vincent declaration are far from being achieved. Much can be done to improve the outcomes of pregnancy within existing resources with better systems and organization of care. However, if significant progress is to be made, it is incumbent upon health-care professionals and health-care commissioners to direct resources specifically at improving pre-pregnancy and maternity services. Research is needed firstly to analyse in greater detail the wealth of data collected in the CEMACH survey and consider the implications of health-care costs. Further research to discover ways of reducing the adverse outcomes is urgently required. The need to educate, motivate and bring about improved pre-pregnancy care in women with diabetes is a priority.


Mitochondrial D-loop mutations and polymorphisms are connected with canine malignant cancers.
Abstract The aim of the conducted investigations was to identify differences in the D-loop nucleotide sequence between neoplastic tissue, normal tissue, and blood and to determine their correlation with the type of cancer in dogs. In 62.5% of the analyzed tumors of epithelial origin and 25% tumors of mesenchymal origin, substitution was detected within the D-loop sequence between the neoplastic tissue, normal tissue, and blood. Two mutations occurring in the carcinogenic process in position T15620C have been identified in epithelioma glandulae sebacei and carcinoma planoepithelialae keratodes. Blood and cancer heteroplasmy was diagnosed for carcinoma planoepithelialae keratodes and "Comedo" carcinoma. The results of the study indicate that polymorphic changes in the D-loop sequence promote carcinogenesis in dogs. Heteroplasmy diagnosed in blood and tumor cells and absence thereof in normal tissue may imply mtDNA recombination. High prevalence of mtDNA mutations in canine tumors may suggest mtDNA genetic instability, which is likely to play a role in carcinogenesis.


Human sulfatase 1 exerts anti-tumor activity by inhibiting the AKT/ CDK4 signaling pathway in melanoma.
Human sulfatase 1 (hSulf-1) has aryl sulfatase activity. It can reduce the sulfation of cell surface heparan sulfate proteoglycan (HSPG) and inhibit various growth factor receptor-mediated signaling pathways. In most cancers, hSulf-1 is inactivated, which endows cancer cells with increasesed cell proliferation and metastatic activities, inhibition of apoptosis, and decreased sensitivity to radio- and chemotherapy. In this study, we found that hSulf-1 overexpression in melanoma cells can inhibit cell proliferation and induce cell cycle arrest and apoptosis by decreasing the protein kinase B (AKT) phosphorylation and limiting CDK4 nuclear import. We further confirmed that hSulf-1 overexpression can inhibit AKT phosphorylation and CDK4 nuclear localization and retard the growth of melanoma xenograft tumors in nude mice. Overall, hSulf-1 function in melanoma cells provides an ideal molecular treatment target. An important anti-tumor mechanism of hSulf-1 operates by decreasing downstream AKT signaling pathway activity and inhibiting the nuclear import of CDK4.


Acute volume expansion enhances baroreceptor discharge in dogs.
By recording single-unit discharge from the carotid sinus nerve of normal dogs in the control and in the volume-expanded state, both with the sinus open to the circulation and with it isolated, the effects of acute volume expansion on baroreceptor discharge sensitivity were investigated. The carotid sinus was vascularly isolated except for the common carotid and external carotid arteries. Inflation of hydraulic occluders on these vessels completely isolated the sinus from the systemic circulation. Flow and diameter changes of the carotid sinus were measured. Plasma volume was expanded with isotonic, isoncotic dextran in normal saline until the left ventricular end-diastolic pressure reached a value of 20-25 mmHg. In the group with the sinus open to the circulation, volume expansion did not depress baroreceptor discharge sensitivity; in fact, it augmented baroreceptor activity (peak discharge = 39.2 +/- 1.6 vs. 49.9 +/- 3.3 spikes/s, P less than 0.05). There was no such effect in the group with the sinus isolated from the circulation during volume expansion. In the group with the sinus open to the circulation, volume expansion significantly increased flow through the common carotid artery and shifted the carotid sinus pressure-diameter curves upward without a change in compliance. These data suggest that acute volume expansion augments baroreceptor discharge, and this phenomenon may be mediated either by some circulating substance(s) or by an increase in flow through the carotid sinus during volume expansion.


So much to learn, so little time: educational priorities for the future of emergency nursing.
The purpose of this study was to examine how and to what extent current societal and healthcare trends impact the educational needs of the emergency nurse. In addition, this study sought to draw upon that information to facilitate the development of expert consensus about the major educational priorities for emergency nurses during the time period from 2008 to 2018. A mixed methodology, qualitative-then-quantitative study design using a Delphi method was employed for this research. The 3-round Delphi study engaged a total of 50 emergency nursing experts with prior experience in emergency nursing practice and education to identify societal and healthcare trends and major educational priorities of relevance to emergency nurses. In this study, 3 rounds of questioning resulted in a total of 42 societal and healthcare priorities and 63 educational priorities with moderate to high consensus achieved in all categories. Societal and healthcare trends that were ranked as having the most significant impact on emergency nursing included emergency department overcrowding, increasing patient complexity and acuity, access to healthcare, mental and behavioral health needs, and an aging population. Educational themes or topics that were ranked as being an extremely high priority for emergency nursing included critical thinking, core emergency nursing competencies, triage, pediatric patient care, medication and patient safety, and individualized orientation programs for emergency nurses. An analysis of the highest priority educational themes indicates that emergency nursing experts are concerned with not only the content of educational programs but also the pedagogy used to provide educational opportunities to current and future emergency nurses.


[Spatio-temporal variations of functional diversity of fish communities in Haizhou Bay.]
As the link among species, ecological environment, and ecosystem function, functional diversity can help us to better understand the relationship between biodiversity and ecosystem function. We analyzed functional diversity with thirteen functional traits reflecting the characteristics of food acquisition, locomotion, ecological adaptation, reproduction and population dynamics of fish species. The seasonal, interannual and spatial variations of functional diversity of fish communities were examined using functional richness index (FRic), functional evenness index (FEve), functional divergence index (FDiv) and community weighted mean index (CWM) based on the data from the bottom trawl surveys in spring and autumn from 2011 to 2017 (except 2012) in Haizhou Bay. The results showed that functional diversity indices were significantly different in spring and autumn, with FRic was significantly higher in autumn than that in spring and FDiv was significantly higher in spring than that in autumn. Migration might be the main reason for the seasonal change of functional diversity indices. CWM analysis showed that dominant fish species were cold-temperate or warm-temperate species, with higher trophic level, strong motion ability, and relatively high growth coefficient, resilience and vulnerability in spring. In autumn, the dominant species showed the opposite traits. In both spring and autumn, fish species with pelagic eggs dominated the fish communities. Inter-annual variations in functional diversity indices were observed in spring and autumn. The functional diversity indices showed an annual fluctuation during the study period in both spring and autumn, indicating the low stability of fish community in Haizhou Bay. Significant spatial changes in functional diversity of fish assemblages were observed, with FDiv being higher in the offshore coastal waters (>20 m) than that in the shallow waters (<20 m). The functional diversity showed obvious spatio-temporal variation. The ecological niches and resource utilization of fish species varied with season, year and space in Haizhou Bay.


Comparison of the effects of albumin 5%, hydroxyethyl starch 130/0.4 6%, and Ringer's lactate on blood loss and coagulation after cardiac surgery.
Infusion of 5% human albumin (HA) and 6% hydroxyethyl starch 130/0.4 (HES) during cardiac surgery expand circulating volume to a greater extent than crystalloids and would be suitable for a restrictive fluid therapy regimen. However, HA and HES may affect blood coagulation and could contribute to increased transfusion requirements. We randomly assigned 240 patients undergoing elective cardiac surgery to receive up to 50 ml kg(-1) day(-1) of either HA, HES, or Ringer's lactate (RL) as the main infusion fluid perioperatively. Study solutions were supplied in identical bottles dressed in opaque covers. The primary outcome was chest tube drainage over 24 h. Blood transfusions, thromboelastometry variables, perioperative fluid balance, renal function, mortality, intensive care unit, and hospital stay were also assessed. The median cumulative blood loss was not different between the groups (HA: 835, HES: 700, and RL: 670 ml). However, 35% of RL patients required blood products, compared with 62% (HA) and 64% (HES group; P=0.0003). Significantly, more study solution had to be administered in the RL group compared with the colloid groups. Total perioperative fluid balance was least positive in the HA group [6.2 (2.5) litre] compared with the HES [7.4 (3.0) litre] and RL [8.3 (2.8) litre] groups (P<0.0001). Both colloids affected clot formation and clot strength and caused slight increases in serum creatinine. Despite equal blood loss from chest drains, both colloids interfered with blood coagulation and produced greater haemodilution, which was associated with more transfusion of blood products compared with crystalloid use only.


GFAP-expressing cells in the postnatal subventricular zone display a unique glial phenotype intermediate between radial glia and astrocytes.
Neural stem cells in the adult subventricular zone (SVZ) derive from radial glia and express the astroglial marker glial fibrillary acidic protein (GFAP). Thus, they have been termed astrocytes. However, it remains unknown whether these GFAP-expressing cells express the functional features common to astrocytes. Using immunostaining and patch clamp recordings in acute slices from transgenic mice expressing green fluorescent protein (GFP) driven by the promoter of human GFAP, we show that GFAP-expressing cells in the postnatal SVZ display typical glial properties shared by astrocytes and prenatal radial glia such as lack of action potentials, hyperpolarized resting potentials, gap junction coupling, connexin 43 expression, hemichannels, a passive current profile, and functional glutamate transporters. GFAP-expressing cells express both GLAST and GLT-1 glutamate transporters but lack AMPA-type glutamate receptors as reported for dye-coupled astrocytes. However, they lack 100 microM Ba2+-sensitive inwardly rectifying K+ (K(IR)) currents expressed by astrocytes, but display delayed rectifying K+ currents and 1 mM Ba2+-sensitive K+ currents. These currents contribute to K+ transport at rest and maintain hyperpolarized resting potentials. GFAP-expressing cells stained positive for both K(IR)2.1 and K(IR)4.1 channels, two major K(IR) channels in astrocytes. Ependymal cells, which also derive from radial glia and express GFAP, display typical glial properties and K(IR) currents consistent with their postmitotic nature. Our results suggest that GFAP-expressing cells in concert with ependymal cells can perform typical astrocytic functions such as K+ and glutamate buffering in the postnatal SVZ but display a unique set of functional characteristics intermediate between astrocytes and radial glia.


Effects of dietary restriction on metabolic and cognitive health.
Life expectancy in most developed countries has been rising over the past century. In the UK alone, there are about 12 million people over 65 years old and centenarians have increased by 85% in the past 15 years. As a result of the ageing population, which is due mainly to improvements in medical treatments, public health, improved housing and lifestyle choices, there is an associated increase in the prevalence of pathological conditions, such as metabolic disorders, type 2 diabetes, cardiovascular and neurodegenerative diseases, many types of cancer and others. Statistics suggest that nearly 54% of elderly people in the UK live with at least two chronic conditions, revealing the urgency for identifying interventions that can prevent and/or treat such disorders. Non-pharmacological, dietary interventions such as energetic restriction (ER) and methionine restriction (MR) have revealed promising outcomes in increasing longevity and preventing and/or reversing the development of ageing-associated disorders. In this review, we discuss the evidence and mechanisms that are involved in these processes. Fibroblast growth factor 1 and hydrogen sulphide are important molecules involved in the effects of ER and MR in the extension of life span. Their role is also associated with the prevention of metabolic and cognitive disorders, highlighting these interventions as promising modulators for improvement of health span.


Freewheel training alters mouse hippocampal cytokines.
The effects of 16 weeks of voluntary wheel running in healthy female mice on hippocampal expression of pro-(TNF-α, IL-1β, IL-12) and anti-(IL-10, IL-1ra) inflammatory and pleiotropic (IL-6) cytokines and apoptotic status of specific cell subsets (CD45+, CD11b+) were studied. Mice were assigned to wheel running (WR; n=20) or a control condition (No WR; n=22) and sacrificed after the 16 weeks. Data collected included measures of training status (running volume, body weight, run-to-exhaustion time, and skeletal muscle cytochrome c oxidase activity), flow cytometric analysis of cell phenotypes and apoptosis (CD45+, CD11b+, Annexin+, Annexin+/PI+, PI+), and cytokine concentrations in cell lysates. WR mice had measurable training effects and significantly lower TNF-α (p<0.05) and higher IL-6 (p<0.05), IL-1ra (p<0.05) and IL-12 (p<0.05) expression in the hippocampus compared to controls. IL-1β, IL-10, and the percent of apoptotic and dead cells did not change due to training. Taken together, and in relation to the complex interactions between cytokines, the results suggest a possible mechanism whereby exercise training may buffer from dementia and cognitive decline through changes in the central cytokine milieu in the hippocampus.


A Large Lumbar Adnexal Neoplasm Presenting Characteristics of Eccrine Poroma and Poroid Hidradenoma.
Poroma is a rare benign neoplasm that derives from eccrine sweat glands epithelium. Its histological subtypes, with respect to its position within skin layers, are eccrine poroma, hidroacanthoma simplex, poroid hidradenoma, and dermal duct tumor. Poromas commonly exhibit benign clinical behavior as they are usually small and asymptomatic and do not exhibit malignant behavior. Although their histological subtypes share similar histological characteristics, they rarely coexist in the same tumor. In this report we present the case of an unusual poroma in terms of histological and clinical behavior as it was large and presented histological characteristic of both eccrine poroma and poroid hidradenoma. Coexistence of different histologic subtypes in the same tumor indicates simultaneous tumorigenesis, differentiation from one cell type to another, or parallel differentiation from a common progenitor cell. Implications in treatment remain unknown partly due to the rarity of such cases.


Quality control assessment of polyherbal formulation based on a quantitative determination multimarker approach by ultra high performance liquid chromatography with tandem mass spectrometry using polarity switching combined with multivariate analysis.
An ultra high performance liquid chromatography with electrospray ionization tandem mass spectrometry method has been developed and validated for the simultaneous quantification of 28 major bioactive compounds in Mentat tablet, a complex Indian herbal medicine used in the treatment of neurological disorder and improvement of mental health. Multiple-reaction monitoring scanning was employed for quantification in positive and negative ion switching mode. The analysis was accomplished on Waters ACQUITY UPLC BEH C18 column with linear gradient elution of water/formic acid (0.1%) and acetonitrile/formic acid (0.1%) at a flow rate of 0.3 mL/min. The proposed method was validated with acceptable linearity (r2 , 0.9984-0.9999), precision (RSD, 0.22-2.11%), stability (RSD, 0.16-1.78%), and recovery (RSD ≤ 3.74%), under optimum conditions. The limits of quantitation ranged from 0.28 to 3.88 ng/mL. The method was successfully applied for simultaneous determination of 28 compounds in 20 batches of Mentat tablet. Hierarchical cluster analysis and principal component analysis were performed to evaluate the similarity and variation of the 20 samples based on the characteristics of 28 bioactive compounds. Results indicated that this method is rapid, sensitive, and reliable to show the quality of the Mentat tablet's composition, hence may be used for quality control of polyherbal formulations having similar markers/raw herbs.


Tongue muscle strength affects posterior pharyngeal wall advancement during swallowing: A cross-sectional study of outpatients with dysphagia.
Tongue muscle strength is important for swallowing but decreases with age, in association with reduced skeletal muscle mass. However, the relationships between pharyngeal dynamics and both skeletal muscle mass and tongue muscle strength are unknown. To investigate the effect of reductions in tongue muscle strength on pharyngeal movement during swallowing in patients with dysphagia. Subjects were selected from male outpatients ≥65 years old who were examined for the main complaint of dysphagia. Patients with history of neurodegenerative disease affecting tongue movement, cerebrovascular disease or oral cancer were excluded. As a result, 82 men (mean age, 80.6 ± 6.8 years) participated. Skeletal muscle mass index (SMI) as physical parameters and maximum tongue pressure (MTP) as tongue muscles strength were measured. Status and dynamics of the pharyngeal organs, including change in posterior pharyngeal wall advancement (PPWA) when swallowing 3.0 mL of moderately thick liquid, were measured by analysing videofluoroscopic images. Simple bivariate correlation and multiple regression analysis were used to statistically analyse correlations between parameters. MTP showed a significant positive correlation with SMI (r = .43, P < .01). PPWA showed a significant negative correlation with MTP (r = -0.30, P < .01), but no association with SMI. While tongue muscle strength is affected by skeletal muscle mass, posterior pharyngeal wall advancement is not readily affected by decreases in skeletal muscle mass. Posterior pharyngeal wall advancement may increase to compensate for swallowing function among individuals with reduced tongue muscle strength.


A cerebroprotective dose of intravenous citrate/sorbitol-stabilized dehydroascorbic acid is correlated with increased cerebral ascorbic acid and inhibited lipid peroxidation after murine reperfused stroke.
Oxidative damage has been implicated in the pathogenesis of cerebral ischemia. We previously demonstrated that exogenously supplied dehydroascorbic acid (DHA), an oxidized, blood-brain barrier transportable form of the antioxidant ascorbic acid (AA), improves outcome after experimental stroke. To investigate the neuroprotective effect of DHA therapy, we measured cerebral AA levels using a novel assay, quantified markers of lipid peroxidation, and evaluated infarct volume after reperfused stroke in a murine model. All experiments were performed using a new citrate/sorbitol-stabilized DHA formulation to improve the stability of the compound. Intraparenchymal AA levels declined after cerebral ischemia/reperfusion and were repleted in a dose-dependent fashion by postischemic administration of intravenous DHA (P < 0.01). Repletion of these levels was associated with reductions in cerebral malondialdehyde levels (P < 0.05), which were also elevated after reperfused stroke. DHA repletion of interstitial AA levels and reduction in cerebral lipid peroxidation was associated with dose-dependent reductions in infarct volume (P < 0.05). Together, these results indicate that an intravenous cerebroprotective dose of citrate/sorbitol-stabilized DHA is correlated with increased brain ascorbate levels and a suppression of excessive oxidative metabolism.


Unravelling the epigenomic interactions between parental inbreds resulting in an altered hybrid methylome in pigeonpea.
DNA methylation is an important heritable landmark conferring epigenetic changes in hybrids and has fascinated biologists and plant-breeders over the years. Although epigenetic changes have been documented in rice and maize hybrids, such investigations have not been reported in pigeonpea. Here, we report genome-wide methylation profiles of pigeonpea sterile and fertile inbred lines and their fertile F1 hybrid at single base resolution. We found that pigeonpea genome is relatively enriched in CG methylation. Identification of differentially methylated regions (DMRs) in the sterile and fertile parent revealed remarkable differences between their methylation patterns. Investigation of methylation status of parental DMRs in hybrid revealed non-additive methylation patterns resulting from trans-chromosomal methylation and trans-chromosomal demethylation events. Furthermore, we discovered several DMRs negatively associated with gene expression in the hybrid and fertile parent. Interestingly, many of those DMRs belonged to transposable elements and genes encoding pentatricopeptide repeats associated proteins, which may mediate a role in modulating the genes impacting pollen fertility. Overall, our findings provide an understanding of two parental epigenomes interacting to give rise to an altered methylome in pigeonpea hybrids, from genome-wide point of view.


Highly activated T-cell receptor AV2S3(+) CD4(+) lung T-cell expansions in pulmonary sarcoidosis.
Sarcoidosis is a systemic disorder of unknown origin, primarily affecting the lungs. The granulomatous inflammation is driven by the interplay between various molecules and cells, including T cells. Previously, our group reported a close correlation between lung-restricted T-cell receptor (TCR) AV2S3 CD4-positive T-cell expansions and HLA-DR17 in active sarcoidosis. The aim of this study was to characterize phenotypically such AV2S3 lung T cells, to obtain more information about the state of activation of this intriguing T-cell subset. Bronchoalveolar lavage (BAL) was performed on sarcoidosis patients with active disease and on healthy control subjects (HC). The expression of activation and subset markers was evaluated and compared between BAL AV2S3-positive and AV2S3-negative T cells of patients with lung-restricted AV2S3 T-cell expansions, and between BAL and peripheral blood lymphocytes (PBL) of patients and HC. The frequency of cells expressing activation markers CD26, CD28, CD69, and HLA-DR was enhanced in AV2S3-positive versus AV2S3-negative BAL CD4(+) T-cell subsets. In contrast, CD25 (Il-2R) and CD27 were expressed at lower levels by the AV2S3-positive CD4(+) lung T cells. Our data confirm a substantial activation of BAL CD4(+) T cells of patients with sarcoidosis. Furthermore, the AV2S3 CD4-positive lung cells display a pattern of activation markers, suggesting that they are significantly more activated compared with lung CD4(+) T cells expressing other TCR V gene segments as well as compared with BAL CD4(+) T cells of HC. These results support our hypothesis of an ongoing and selective stimulation of AV2S3 T cells by a specific antigen and the participation of this subset in the inflammatory process in the lungs of patients with sarcoidosis.


Orthopaedic manifestations of neurofibromatosis type 1: A case report.
Neurofibromatosis type 1 (NF1) or von Recklinghausen disease is one of the most common autosomal dominant genetic diseases. It is characterized by 'café-au-lait' spots and multiple tumors starting from the central and peripheric nervous system. The diagnosis is determined on two out of seven criteria: i) A total of 6 or more light brown spots larger than 5 mm in diameter (pre-puberty) or 15 mm in diameter (post-puberty); ii) a total of 2 or more neurofibromas or one plexiform neurofibroma; iii) axillary or inguinal freckling; iv) optic glioma; v) a total of 2 or more Lisch nodules; vi) bone abnormalities: tibia pseudarthrosis or dysplasia of the sphenoid wing; and vii) a relative of first degree having an NF1 diagnosis. A total of ~50% of patients have significant musculoskeletal manifestation, with scoliosis and congenital pseudarthrosis of tibia most common. Management of the orthopaedic manifestations of NF1 is often difficult. Due to NF1 influencing multiple organ systems, patients are likely to benefit most from a multidisciplinary treatment strategy.


Analysis of risk factors for 90-day mortality after surgery in elderly patients with intertrochanteric fractures and a history of cardiovascular disease.
This study explored the risk factors for all-cause mortality 90 days after surgery in elderly patients with intertrochanteric fractures and a history of cardiovascular disease. We retrospectively analyzed the clinical data of 166 elderly patients with intertrochanteric fractures who were admitted to the Department of Orthopedics of Sichuan Provincial People's Hospital (Eastern Hospital) between January 1, 2010 and December 31, 2014. Kaplan-Meier survival curve analysis and the logrank test were used to compare all-cause mortality in the 90-day postoperative period for elderly patients with intertrochanteric fractures and a history of cardiovascular disease. In addition, we used the Cox proportional hazards model to explore related risk factors and their relative hazard rate (HR). A multivariate Cox regression model was established for elderly patients with intertrochanteric fractures and a history of cardiovascular disease and all-cause mortality within 90 days after surgery. The risk factors suggested by the model were length of hospital stay (HR =1.07, Z=4.26, P<0.001), N-terminal pro brain natriuretic peptide (NT-proBNP) (HR =1.01, Z=4.61, P<0.001), and high-density lipoprotein (HDL) (HR =0.41, Z=2.05, P=0.042). The area under the working curve (AUC) of the Cox regression model was 0.91. The Kaplan-Meier survival curves grouped by length of stay, NT-proBNP, and HDL risk factors were significantly different (P<0.05). As the length of hospital stay increased, abnormally elevated NT-proBNP significantly increased all-cause mortality within 90 days after surgery, while elevated HDL significantly reduced patient mortality. The results of our study suggested that the combination of these 3 indicators could be used as a sensitive predictor for prognosis in elderly patients with intertrochanteric fracture surgery and a history of cardiovascular disease.


Production of scaffold-free cell-based meat using cell sheet technology.
In the production of cell-based meat, it is desirable to reduce animal-derived materials as much as possible to meet the challenges of sustainability. Here, we demonstrate the "cell sheet-based meat": scaffold-free cell-based meat using cell sheet technology and characterize its texture and nutrients. Bovine myoblast cell sheets were prepared using temperature-responsive culture dishes (TRCDs) and 10 stacked cell sheets to fabricate three-dimensional tissue of 1.3-2.7 mm thickness. Hardness was increased by incubation on the TRCD and was further increased by boiling as is characteristic of natural meat. The wet weight percentage of total protein in the cell sheet was about half that of beef. In this method, large-sized items of cell sheet-based meat were also created by simply scaling up the TRCD. This method promises an environment-friendly food product.


Enhancing embryo yield in superovulated holstein heifers by immunization against inhibin.
Eight heifers, aged 16-17 months and showing normal oestrous cycles, were immunized against a recombinant porcine inhibin alpha subunit immunogen, together with another 10 heifers of the same age as controls and treated with placebo immunogen. Primary (1 mg immunogen) and two booster (0.5 mg immunogen each) immunizations were administered at 28-day intervals. Ten days after the second booster immunization, both groups of heifers underwent a superovulation treatment. Each animal was given an intravaginal progesterone releasing sponge, which was withdrawn 7 days following an i.m. injection of 0.5 mg cloprostenol. Heifers were treated with FSH for 4 days and artificially inseminated after oestrus occurred. The embryos were flushed and evaluated 7 days after insemination. Immunization significantly (p < 0.01) increased blood antibody titres against recombinant porcine inhibin alpha subunit, from pre-immunizaion and control values of approximately 0.06 of ELISA 450 nm reading to 0.6 to 0.7 after two or three immunizations. The immunized heifers produced on average 15.8 +/- 2.8 embryos, significantly (p < 0.05) higher than the yield of 8.3 +/- 1.5 in the controls. The number of transferable embryos were non-significantly higher in immunized than in control heifers (9.6 +/- 3.1 vs 5.8 +/- 1.6, p > 0.05). The peak plasma oestradiol concentrations were significantly higher in immunized than in control heifers, both immediately after FSH treatment and 20 days thereafter. Plasma P4 concentrations after superovulation were in the range of 20 ng / ml in the immunized heifers, significantly (p < 0.05) higher than the values approximately 15 ng / ml in control heifers. These results indicated that prior immunization against inhibin alpha subunit stimulated production of antibodies against inhibin, which enhanced follicular developmental response to superovulation and lead to higher yield of total and transferable embryos. Therefore immunization combined with the conventional superovulatory gonadotrophin treatment, can be a simple and efficient method to produce low cost bovine embryos.


Osteopathic Manipulative Treatment for a Recognizable Pattern of Somatic Dysfunction Following Laparoscopic Cholecystectomy.
Previous literature has demonstrated the prevalence and socioeconomic impact of postoperative pain in surgery patients. Somatic dysfunction has been demonstrated as a cause, but literature documenting osteopathic manipulative treatment (OMT) in surgery patients is lacking. To describe typical patterns of and common treatments for somatic dysfunction in patients following laparoscopic cholecystectomy. The authors retrospectively reviewed the billing records of all patients over 18 years of age who underwent laparoscopic cholecystectomy by a single surgeon and had postoperative outpatient OMT for right-side pain linked to somatic dysfunction between 2006 and 2018 at a community hospital in Grand Rapids, Michigan. Patients who underwent open cholecystectomy, who did not have documented somatic dysfunction, or had somatic dysfunction unrelated to their biliary disease were excluded. Nine patients were selected for inclusion in this retrospective case series. All patients in the study demonstrated anterior right lower rib pain corresponding to posterior lower rib dysfunctions and rotated right and side-bent left thoracic spine dysfunctions between T5 and T11. Pain was successfully managed with muscle energy, high-velocity, low-amplitude, or soft tissue OMT. Postoperative pain following laparoscopic cholecystectomy can be related to right-sided thoracic and rib dysfunctions. This is important for early diagnosis of surgical patients with somatic dysfunction and initiation of appropriate OMT to decrease morbidity related to pain, functional status, and quality of life.


Antimitochondrial autoantibodies in pemphigus vulgaris: a missing link in disease pathophysiology.
A loss of epidermal cohesion in pemphigus vulgaris (PV) results from autoantibody action on keratinocytes (KCs) activating the signaling kinases and executioner caspases that damage KCs, causing their shrinkage, detachment from neighboring cells, and rounding up (apoptolysis). In this study, we found that PV antibody binding leads to activation of epidermal growth factor receptor kinase, Src, p38 MAPK, and JNK in KCs with time pattern variations from patient to patient. Both extrinsic and intrinsic apoptotic pathways were also activated. Although Fas ligand neutralizing antibody could inhibit the former pathway, the mechanism of activation of the latter remained unknown. PV antibodies increased cytochrome c release, suggesting damage to mitochondria. The immunoblotting experiments revealed penetration of PVIgG into the subcellular mitochondrial fraction. The antimitochondrial antibodies from different PV patients recognized distinct combinations of antigens with apparent molecular sizes of 25, 30, 35, 57, 60, and 100 kDa. Antimitochondrial antibodies were pathogenic because their absorption abolished the ability of PVIgG to cause keratinocyte detachment both in vitro and in vivo. The downstream signaling of antimitochondrial antibodies involved JNK and late p38 MAPK activation, whereas the signaling of anti-desmoglein 3 (Dsg3) antibody involved JNK and biphasic p38 MAPK activation. Using KCs grown from Dsg3(-/-) mice, we determined that Dsg3 did not serve as a surrogate antigen allowing antimitochondrial antibodies to enter KCs. The PVIgG-induced activation of epidermal growth factor receptor and Src was affected neither in Dsg3(-/-) KCs nor due to absorption of antimitochondrial antibodies. These results demonstrated that apoptolysis in PV is a complex process initiated by at least three classes of autoantibodies directed against desmosomal, mitochondrial, and other keratinocyte self-antigens. These autoantibodies synergize with the proapoptotic serum and tissue factors to trigger both extrinsic and intrinsic pathways of cell death and break the epidermal cohesion, leading to blisters. Further elucidation of the primary signaling events downstream of PV autoantigens will be crucial for the development of a more successful therapy for PV patients.


Impact of Medicare's prospective payment system and the farm crisis on the health care of the elderly: a case study.
The spectrum of health care for the rural elderly has been negatively affected by recent changes in Medicare reimbursement policies and by the farm crisis. This case study examined the effects of these changes on the ability of rural hospitals, the aging network, and care-givers to provide adequate and continuous care to the elderly. In this case study, three gaps in services were found: a lack of programs designed to meet the needs of terminally ill patients and their families; a lack of education during the crucial transitional period between hospital discharge and home; and a lack of services and programs for the chronically-ill older adult. More studies are needed to determine if similar service gaps will be found in other rural communities. If so, public attention should be focused on possible solutions.


[Immunomorphological features of chronic tonsillitis].
The objective of the present work was to overview current concepts of immunology and pathological morphology of chronic tonsillitis. Morphological aspects of embryological development of palatine tonsils are discussed in conjunction with their participation in the formation of the immune response. Morphological and immunological peculiarities of the pathological process in chronic tonsillitis are described. It is concluded that otorhinolaryngologists must in due time identify indications for radical surgical sanitation of the pockets of chronic infection by means of bilateral tonsillectomy.


Dynamics in the isomerization of intramolecular DNA triplexes in supercoiled plasmids.
We report here kinetic and thermodynamic studies on differential isomerization of intramolecular Pyr*Pur.Pyr triplexes in supercoiled plasmids. Two structural isomers of the triplex exist: one with the 3'-half of the Pyr strand as the third strand (H-y3 form) and the other with the 5'-half as the third strand (H-y5 form). The relative populations of the two triplex isomers was determined using the chemical probe with diethyl pryrocarbonate as a function of incubation time. The results demonstrated that triplexes were formed rapidly after a pH change from pH 8.0 to 5.0 and that the initial population of the two isomers exponentially changed with incubation time to reach true thermodynamic equilibrium with a time constant of 0.6-10 h, depending on temperature and the presence of Mg2+. The results clearly demonstrated that interconversion occurs between the two isomers and that the presence of Mg2+ generally retarded the interconversion rates. Kinetic and thermodynamic analyses of the relative populations of the two isomers revealed that the apparent energy barrier for transition from duplex to the H-y3 form is higher than that to the H-y5 form, but H-y3 is more stable in enthalpy terms than H-y5. Therefore, H-y3 is kinetically inferior but thermodynamically favored at higher supercoil levels in plasmids. The presence of Mg2+ resulted in both a kinetic and a thermodynamic preference for H-y5 formation, relative to the H-y3 form.


Closing the Gaps: competing estimates of Indigenous Australian life expectancy in the scientific literature.
Closing the gap in life expectancy between Indigenous and other Australians within a generation is central to national Indigenous reform policy (Closing the Gap). Over time, various methods of estimating Indigenous life expectancy and with that, the life expectancy gap, have been adopted with differing, albeit non-comparable results. We present data on the extent of the gap and elucidate the pattern of use and interpretations of the different estimates of the gap, between 2007 and 2012. An extensive search was conducted for all peer-reviewed health publications citing estimates of and/or discussing the life expectancy of Indigenous Australians, for the period 2007-2012. Five predominant patterns of citation of the gap estimates were identified: 20 years, 17 years, 15-20 years, 13 years, and 11.5 years for males and 9.7 years for females. Some authors misinterpret the most recent estimates as reflecting improvement from the 17-year figure, rather than the result of different methods of estimation. Support for the direct methods used to calculate Indigenous life expectancy is indicated. A specific estimate of the life expectancy gap has not been established among stakeholders in Indigenous health. Agreement on the magnitude of the gap is arguably needed in order to evaluate strategies aimed at improving health outcomes for Indigenous Australians. Moreover, measuring progress towards 'closing the gap' depends on the availability of comparable estimates, using the same techniques of measurement to assess changes over time.


The role of physiotherapy in fibromyalgia: Current and future perspectives.
Fibromyalgia is a chronic pain condition characterized by generalized musculoskeletal pain, hyperalgesia and allodynia, commonly associated with other symptoms such as fatigue, poor sleep quality, anxiety and depression. The clinical manifestations of this rheumatic disease have significant psychosocial and economic repercussions, with a substantial impact on health status, quality of life and social activities. Currently, recommendations for the management of fibromyalgia include patient education and non-pharmacological interventions, and among the indicated treatments, clinical guidelines include several physiotherapeutic resources, essential for individuals affected by this syndrome. Research in the physiotherapy field has demonstrated its effectiveness, but there is a need to update the literature. This study aims to identify the effectiveness of physiotherapy in the treatment of individuals with fibromyalgia. We performed a literature review looking for articles dated from March 2012 to March 2022 using the terms "fibromyalgia", "physiotherapy", "physical therapy", "rehabilitation" in different languages in various databases and their main information was read and collected and presented in a descriptive way. The effects of physiotherapy interventions are summarized in order to provide a reference for future research and clinical application. Research on non-pharmacological physiotherapy-oriented treatments has grown in recent years as an alternative for fibromyalgia treatment. This review allows fibromyalgia patients to receive appropriate physical therapy interventions to promote their health.


The effect of women's labor force participation on the distribution of income in the United States.
The effect of women's labor force participation on income distribution in the United States is reviewed. "Because the wives of highly paid men participate less in the labor force, the earnings of working wives make the distribution of pretax, money income more equal for families than it might otherwise be. Although there is considerable speculation that future developments in women's labor force participation may foster greater inequality, the empirical results are mixed." The factors that need to be considered in future research are outlined.


Incidence, density and direction of hair on the dorsum of phalanges of the hands in Malays.
In this study 200 Malay subjects (100 males and 100 females) were randomly selected from patients attending outpatient clinics of Hospital USM, Kelantan, Malaysia, to find out the incidence, density and direction of hair on the dorsum of phalanges of the hand. These features have not been studied so far in females nor has such a study been conducted in Malays. The probability of density of hair distribution among the digits of both hands showed significant correlation on proximal phalanges (p < 0.05) in both sexes. Significant correlation was not observed, however, in the middle phalangeal hair (MPH) of the hands. The direction of proximal phalangeal hair, from little finger to the thumb, showed significant changes from ulnar to radial in both sexes (p < 0.05). Identification of isolated digits, which is of medicolegal importance, would be more accurate if the direction and the density of hair on the digits are both considered together. MPH was present in 48% of males and in 33% of females studied. Comparisons with presence of MPH in other populations show that Malays are ethnically similar to other Asiatic populations.


Intensive, very short-term chemotherapy for advanced Burkitt's lymphoma in children.
To improve the 63% event-free survival (EFS) achieved before 1986 in Murphy's stage III to IV Burkitt's lymphoma (BL), both chemotherapy and supportive care were intensified. From May 1987 to February 2001, 60 children, median age 9 years (range, 2.1 to 17 years), with advanced BL were enrolled onto two sequential institutional studies. From 1987 to 1992, 30 patients were stratified according to the absence (regimen IA, n = 19) or presence (regimen IB, n = 11) of bone marrow (BM) or CNS involvement. After 5-week cytoreductive chemotherapy consisting of vincristine, cyclophosphamide, doxorubicin, high-dose (HD) methotrexate (MTX), and intrathecal MTX or cytarabine, HD cytarabine and cisplatin were provided as a 4-day continuous infusion. Regimen IB was intensified by adding etoposide and HD ifosfamide and escalating MTX doses. Since 1992, regardless of BM or CNS status, 30 patients have been placed on regimen II, which is identical to IB but without ifosfamide. The scheduled duration of regimen II was 45 days. EFS and disease-free survival at 5 years are 81% +/- 5% and 87% +/- 5%, respectively, for 59 assessable patients (73% +/- 8% and 85% +/- 7% for regimen IA + IB, 89% +/- 6%, EFS and disease-free survival, for regimen II; median follow-up, 6.7 years; range, 0.6 to 13.5 years). Six patients, two of whom were receiving regimen II, died as a result of initial treatment failure or relapse, and five patients, none receiving regimen II, died as a result of treatment-related complications. This 45-day intensive chemotherapy program is the shortest schedule for disseminated BL and overcomes previously recognized risk factors such as BM and CNS infiltration.


Fractional statistics and quantum scaling properties of the Hubbard chain with bond-charge interaction.
We present a detailed study of the ground state and low-temperature properties of the integrable Hubbard model with bond-charge interaction, including its conducting properties and scaling behavior near the U-driven quantum phase transitions. Remarkably, the model displays fractional statistical properties, which enlighten the nature of various physical properties, such as the fractional elementary excitations, and give rise to a disordered condensate and phase separation in k space, as well as to a topological change in the generalized Fermi surface at half filling.


Effects of four antihypertensive monotherapies on cardiac mass and function in hypertensive patients with left ventricular hypertrophy: randomized prospective study.
To compare the effects of four antihypertensive drugs, which have reportedly different effectiveness in reducing myocardial mass. A randomized, double-blind, prospective study included 80 hypertensive patients with left ventricular (LV) hypertrophy confirmed both electrocardiographically and echocardiographically. We investigated the effects of indapamide, nicardipine, propranolol, and chlorthalidone on arterial blood pressure and LV mass and function. Sixty-four patients (34 men and 30 women) completed the 6-month study. No significant differences in antihypertensive effects of the four medications were found. The average decrease in systolic and diastolic blood pressure was 12.8% and 10.4%, respectively. All four antihypertensive medications caused pronounced reduction in LV mass, between 7.9% in the propranolol group and 10.1% in the nicardipine group, with no significant difference between the groups. In patients receiving diuretics, predominant decrease was observed in LV mass and LV mass index. In patients treated with propranolol, the thickness of both the LV wall and interventricular septum was reduced, whereas the reduction in LV mass, LV wall and interventricular septum thickness was found in patients treated with nicardipine. There was no significant correlation between the changes in LV mass and other variables (blood pressure, and systolic and diastolic function). Systolic function did not improve with the reversion of LV hypertrophy in any group of patients, but improvement was observed in some indices of diastolic function. The early and late LV filling velocity and their ratio did not improve significantly, either. Clinically relevant side effects were not observed. All four antihypertensive monotherapies achieved a comparable control of hypertension and reduction in LV hypertrophy.


Vitamin E and levocarnitine as prophylaxis against doxorubicin-induced cardio toxicity in the adult cancer patient: A review.
Doxorubicin, a component of the anthracycline group, is a highly effective in the treatment of hematologic and solid malignancies. Because of the cardiotoxic adverse effects, use is limited. Antioxidants may negate this anthracycline-induced cardiotoxicity, although the literature is not conclusive with regards to the cardioprotective benefits of antioxidants. This review assessed and mapped evidence of the efficacy of vitamin E and levocarnitine against doxorubicin-induced cardiotoxicity in adult cancer patients. This review was based on the Arksey and O'Malley methodology. Potentially relevant literature in English published between January 1960 and April 2021 was identified through a database search. Oxford Quality Scoring System and AMSTR2 were used to assess the quality of trials and systematic reviews respectively, as well as the risks of potential bias. Nineteen of the 10 268 (0.2%) articles from the initial search were included in the final analysis (12 clinical trials and 7 systematic reviews). Vitamin E was included in seven prospective clinical trials. Levocarnitine was included in five clinical trials as an individual agent and a single trial as a combination treatment. No trials could be found investigating the combination of vitamin E and levocarnitine in humans. This review found that levocarnitine trials showed some cardioprotective effects but the results from vitamin E trials were controversial and inconclusive. Most of the trials reviewed had some shortcomings. Further investigations are therefore needed to determine the efficacy of vitamin E and levocarnitine in preventing doxorubicin-induced cardiotoxicity in adult cancer patients.


Effects of particle size and dry matter content of a total mixed ration on intraruminal equilibration and net portal flux of volatile fatty acids in lactating dairy cows.
Effects of physical changes in consistency of ruminal contents on intraruminal equilibration and net portal fluxes of volatile fatty acids (VFA) in dairy cows were studied. Four Danish Holstein cows (121+/-17 d in milk, 591+/-24 kg of body weight, mean+/-SD) surgically fitted with a ruminal cannula and permanent indwelling catheters in the major splanchnic blood vessels were used. The experimental design was a 4x4 Latin square with a 2x2 factorial design of treatments. Treatments differed in forage (grass hay) particle size (FPS; 3.0 and 30 mm) and feed dry matter (DM) content of the total mixed ration (44.3 and 53.8%). The feed DM did not affect chewing time, ruminal variables, or net portal flux of VFA. However, decreasing the FPS decreased the overall chewing and rumination times by 151+/-55 and 135+/-29 min/d, respectively. No effect of the reduced chewing time was observed on ruminal pH or milk fat percentage. Cows maintained average ventral ruminal pH of 6.65+/-0.02, medial ruminal pH of 5.95+/-0.04, and milk fat of 4.42+/-0.12% with chewing time of 28.0+/-2.1 min/kg of DM when fed short particles. The medial ruminal pool of wet particulate matter was decreased by 10.53+/-2.29 kg with decreasing FPS, thereby decreasing the medial pool of total VFA, acetate, propionate, butyrate, isobutyrate, and isovalerate by 1,143+/-333, 720+/-205, 228+/-69, 140+/-51, 8.0+/-2.3, and 25.2+/-5.6 mmol, respectively. Ventral pool variables were not affected by treatments. Relatively large intraruminal differences of VFA concentrations and pH between the ventral and medial pools were observed, VFA concentrations being largest and pH being the lowest medially. This indicates that the ruminal mat acts as a barrier retaining VFA. The effects of reduced FPS were limited to the VFA pool sizes of the mat, leaving ruminal pH, ruminal VFA concentrations, and net portal flux of VFA unaffected. Consequently reduced FPS affected the intraruminal equilibration of VFA between mat and ventral rumen with an estimated turnover rate of isobutyrate increasing from 66+/-3%/h with long particles to 81+/-3%/h [corrected] with short particles. The estimated ruminal fluid flow and therefore intraruminal VFA transport between medial and ventral phase was not affected by the FPS. In conclusion, the ruminal mat pool of VFA was proportional to the size of the mat and the only detected effects of decreasing FPS were decreasing the mat size and an increasing turnover of the mat pool of VFA.


Structured and unstructured viva voce assessment: A double-blind, randomized, comparative evaluation of medical students.
The proper assessment orients learning in the desired direction. The structuring of assessment tools helps in minimizing the examination bias. However, the structuring of viva voce (SVV) has not been tried much. Therefore, this study was conducted to comparatively evaluate the structured written theory examination (STE) outcome with structured and unstructured viva voce assessments in third semester MBBS students. Twenty uniform viva voce cards each containing eight structured questions with equitable, progressive cognitive levels were prepared. The random permutation (randomization) was done by shuffling the cards before the student picked up one card in a double-blind fashion. Of 135 students, 33-35 students per day were assessed for 4 continuous days through checklist-based evaluation by the same examiner following the STE. Parallel unstructured practical viva voce assessment was done for a major practical exercises held. The intragroup percentage coefficient of variance values progressively increased in order of unstructured practical viva assessment (UPA%, 18.25) < structured written theory examination (STE%, 47.26) < structured theory viva voce (SVV%, 63.91). Thus, SVV% is more discriminatory than UPA%. The students in appropriate categories were 72 (53%) in%vSTE-SVV, 18(13%) in %vSTE-UPA, and 20 (14%) in %vSVV-UPA, respectively. A very high statistically significant correlation (P = 0.001) is seen between STE% and SVV% and highest erroneous results are seen in %vSVV-UPA (110, 81%). The SVV provides uniform, equitable, unbiased, and reflective assessment of students. Thus, a comprehensive objective and meaningful assessment can be achieved by structuring of written theory, practical, and viva voce.


A stable aberrant immunophenotype characterizes nearly all cases of cutaneous T-cell lymphoma in blood and can be used to monitor response to therapy.
BACKGROUND: Abnormal variations in the expression level of some commonly expressed T-cell antigens are a feature of many T-cell malignancies. METHODS: We sought to assess the frequency of such abnormal antigen expression by flow cytometry in peripheral blood (PB) samples from patients with mycosis fungoides (MF) and Sézary syndrome (SS). We correlated presence of morphologically identifiable tumor cells on PB smear with the frequency of abnormalities in the level of expression of CD3, CD4, CD7, CD8 and CD26. We also examined the degree of stability of these abnormal findings in tumor cells over the course of disease. The flow cytometric findings in 100 PB samples from 44 patients, including 38 who had multiple sequential PB samples (2-8 samples each), were assessed. RESULTS: Abnormalities were seen in the expression level of one or more T-cell markers in 41 cases (93%) including CD3 in 34% of patients, CD4 in 54%, CD26 in 86% and CD 45 in 40% (10 cases tested). In all but 2 cases, the abnormal T-cell immunophenotype remained similar over the course of treatment and correlated with the relative numbers of tumor cells counted on PB smear. CONCLUSIONS: Using a standard T-cell panel, stable phenotypically aberrant T-cell populations representing the tumor are detected in the vast majority of involved PB samples in MF/SS and can be used to monitor response to therapy.


The NACI Registry: an instrument for the evaluation of new approaches to coronary intervention. The NACI Investigators.
The New Approaches to Coronary Intervention (NACI) Registry was developed to collect in-depth data about patients whose coronary artery lesions are being treated with new interventional techniques such as atherectomy, stents, and laser devices. The NACI Registry database distinguishes among several possible "modes" for device use, such as preparatory, planned definitive, and bailout use. Common definitions are used for data collection across all devices, and device-specific forms are used to record procedural details. NACI's unique modular form design facilitates thorough data collection, even for the most complex treatment scenarios. The database structure allows for data analysis at the patient, procedure, lesion, and device levels, as required to perform in-depth analyses of the immediate and long-term success of new devices. Once adequate knowledge of basic device performance has been collected, the Registry structure can also allow expeditious planning and performance of randomized trials comparing a new device to conventional PTCA.


Partial sequence analysis of the L1 gene of bovine papillomavirus type 1 detected by PCR with MY09/MY11 primers in equine sarcoids in Poland.
BPV-1 is now recognized as a main etiological agent of equine sarcoids. The etiopathogenesis of the equine sarcoids is equivocal and is not yet fully understood. The aim of the present study was to analyse a partial sequence of the L1 gene of BPV associated with equine sarcoids in Polish horses. After clinical diagnosis, 40 skin lesions obtained from 29 horses were collected. The amplicons of a fragment of BPV L1 DNA were detected using PCR with MY09/MY11 primers in 31 specimens. All of them were recognized as BPV-1. Phylogenetic analysis has allowed the amplicons of partial L1 gene to be divided into 3 phylogenetic groups (A, B, C) and one separate isolate (20c). Sequence variants from phylogenetic groups B, C and isolate 20c represented new genetic variants of BPV-1 L1. Sequence variants from groups B and C were submitted to GenBank NCBI.


Development and evaluation of a web site to improve recovery from hysterectomy.
Following surgery, information received upon discharge for recovery at home varies depending on the hospital, and the information is typically given to the patient all at once rather than timed to the recovery process. To address these information challenges, a Web site to help women recovering at home after hysterectomy was developed and evaluated. The Web site was designed to guide the hysterectomy patient through her postsurgical recovery by providing timely and relevant information tailored to the patient's stage of recovery. The Web site required patients to complete a checkup assessing 18 symptoms related to their recovery, and advice was given on how to deal with any symptom the patient had. The Web site also provided care tips specific to the patient's day of recovery along with general information regarding hysterectomy and recovery. Thirty-one women participated in the evaluation, which consisted of preoperative and postoperative surveys as well as a telephone interview. Results indicated that patients frequently used and were highly satisfied with the Web site. Patients reported that the Web site was easy to use and informative, helped to guide their recovery, reduced worry and anxiety, and helped to inform decisions of when and how to contact health professionals. Based on the findings, the Web site represents a potentially cost-effective means to aid women recovering from hysterectomy.


Predicting Thermal Adaptation by Looking Into Populations' Genomic Past.
Molecular evolution offers an insightful theory to interpret the genomic consequences of thermal adaptation to previous events of climate change beyond range shifts. However, disentangling often mixed footprints of selective and demographic processes from those due to lineage sorting, recombination rate variation, and genomic constrains is not trivial. Therefore, here we condense current and historical population genomic tools to study thermal adaptation and outline key developments (genomic prediction, machine learning) that might assist their utilization for improving forecasts of populations' responses to thermal variation. We start by summarizing how recent thermal-driven selective and demographic responses can be inferred by coalescent methods and in turn how quantitative genetic theory offers suitable multi-trait predictions over a few generations via the breeder's equation. We later assume that enough generations have passed as to display genomic signatures of divergent selection to thermal variation and describe how these footprints can be reconstructed using genome-wide association and selection scans or, alternatively, may be used for forward prediction over multiple generations under an infinitesimal genomic prediction model. Finally, we move deeper in time to comprehend the genomic consequences of thermal shifts at an evolutionary time scale by relying on phylogeographic approaches that allow for reticulate evolution and ecological parapatric speciation, and end by envisioning the potential of modern machine learning techniques to better inform long-term predictions. We conclude that foreseeing future thermal adaptive responses requires bridging the multiple spatial scales of historical and predictive environmental change research under modern cohesive approaches such as genomic prediction and machine learning frameworks.


Pity, modernity and the spectacle of suffering.
The concept of dignity is often invoked in relation to ideas about a "good" death and, indeed, a "good" life. In this article, I discuss the question of dignity in relation to the rights of the individual in the modern world. This world is one where the relationship of individuals to society is contested in the context of medicine, with all its technologies of treatment and uncertainties of prognosis. For patients who criticize or oppose medicine in order to recover their dignity, it is necessary to articulate or to portray their suffering. In this way, they are able to show not only that they live in spite of illness, but that they also live by virtue of it. From this perspective, dignity is shown to be part of a collective response to a medicalized world in which ideas about illness and health are also being transformed.


Role of the CpxAR two-component signal transduction system in control of fosfomycin resistance and carbon substrate uptake.
Although fosfomycin is an old antibiotic, it has resurfaced with particular interest. The antibiotic is still effective against many pathogens that are resistant to other commonly used antibiotics. We have found that fosfomycin resistance of enterohemorrhagic Escherichia coli (EHEC) O157:H7 is controlled by the bacterial two-component signal transduction system CpxAR. A cpxA mutant lacking its phosphatase activity results in constitutive activation of its cognate response regulator, CpxR, and fosfomycin resistance. We have shown that fosfomycin resistance requires CpxR because deletion of the cpxR gene in the cpxA mutant restores fosfomycin sensitivity. We have also shown that CpxR directly represses the expression of two genes, glpT and uhpT, which encode transporters that cotransport fosfomycin with their native substrates glycerol-3-phosphate and glucose-6-phosphate, and repression of these genes leads to a decrease in fosfomycin transport into the cpxA mutant. However, the cpxA mutant had an impaired growth phenotype when cultured with glycerol-3-phosphate or glucose-6-phosphate as a sole carbon substrate and was outcompeted by the parent strain, even in nutrient-rich medium. This suggests a trade-off between fosfomycin resistance and the biological fitness associated with carbon substrate uptake. We propose a role for the CpxAR system in the reversible control of fosfomycin resistance. This may be a beneficial strategy for bacteria to relieve the fitness burden that results from fosfomycin resistance in the absence of fosfomycin.


The perioperative patient on buprenorphine: a systematic review of perioperative management strategies and patient outcomes.
An increasing number of patients with opioid use disorder (OUD) are treated with opioid agonist-antagonists such as buprenorphine/naloxone. Perioperative management of patients on buprenorphine/naloxone is inconsistent and remains a controversial topic with mismanagement posing a significant risk to the long-term health of these patients. We performed a systematic literature search involving Medline, Medline In-Process, Embase, Cochrane Central, Cochrane Database of Systematic Reviews, PsycINFO, Web of Science (Clarivate), Scopus (Elsevier), CINAHL (EbscoHosst), and PubMed (NLM). Eighteen studies were included in the final sample, including one controlled study and four observational studies . Neither the controlled study nor the observational studies assessed addiction treatment retention, harm reduction, or long-term mortality rates as primary or secondary outcomes. Of the observational studies, authors showed equivalent peri- and postoperative pain control among buprenorphine continued patients. All but one authors described adequate analgesia among the case reports in which buprenorphine ≤ 16 mg sublingually (SL) daily was continued during the perioperative period. Long-term harm reduction was not reported with only three case reports including any long-term abstinence or relapse rates. The current understanding of the risks and benefits of continuing or stopping buprenorphine perioperatively is limited by a lack of high-quality evidence. Observational studies and case reports indicate no evidence against continuing buprenorphine perioperatively, especially when the dose is < 16 mg SL daily. In patients with significant potential for relapse, such as those with a recent history of OUD, the discontinuation of buprenorphine should have a strong rationale supported by patient and surgical preferences. Future studies require standardized reporting of median doses, details on the route of delivery, dosing schedules and any dosing changes, and rates of addiction relapse, including long-term morbidity and mortality where possible.


Virus-neutralizing antibodies to hepatitis C virus.
For a long time, the lack of an appropriate cell culture system has hampered the study of neutralizing antibody responses against hepatitis C virus (HCV). However, the last decade has seen the development of several model systems that have significantly advanced our understanding of viral entry and antibody neutralization. Studies of acutely infected patients suggest that a strong and early production of neutralizing antibodies may contribute to control the virus during the acute phase of HCV infection and facilitate viral elimination by cellular immune responses. It also emerges that the early antibody response mainly targets hypervariable region 1 (HVR1) of the envelope glycoprotein E2. This host response can lead to viral escape from neutralization by rapid amino acid changes in this hypervariable region. In contrast, cross-reactive neutralizing antibodies seem to appear later during HCV infection, and several mechanisms contribute to reduce their accessibility to their cognate epitopes. These include the masking of major conserved neutralizing epitopes by HVR1, specific N-linked glycans and the lipid moiety of the viral particle. Other potential mechanisms of evasion from the neutralizing antibody response include a modulation by high-density lipoproteins and interfering antibodies as well as the capacity of the virus to be transferred by cell-to-cell contacts. Finally, the recent identification of several highly conserved neutralizing epitopes provides some opportunities for the design and development of vaccine candidates that elicit a protective humoral immune response.


Spatio-temporal profile, phenotypic diversity, and fate of recruited monocytes into the post-ischemic brain.
A key feature of the inflammatory response after cerebral ischemia is the brain infiltration of blood monocytes. There are two main monocyte subsets in the mouse blood: CCR2+Ly6Chi "inflammatory" monocytes involved in acute inflammation, and CX3CR1+Ly6Clo "patrolling" monocytes, which may play a role in repair processes. We hypothesized that CCR2+Ly6Chi inflammatory monocytes are recruited in the early phase after ischemia and transdifferentiate into CX3CR1+Ly6Clo "repair" macrophages in the brain. CX3CR1GFP/+CCR2RFP/+ bone marrow (BM) chimeric mice underwent transient middle cerebral artery occlusion (MCAo). Mice were sacrificed from 1 to 28 days later to phenotype and map subsets of infiltrating monocytes/macrophages (Mo/MΦ) in the brain over time. Flow cytometry analysis 3 and 14 days after MCAo in CCR2-/- mice, which exhibit deficient monocyte recruitment after inflammation, and NR4A1-/- BM chimeric mice, which lack circulating CX3CR1+Ly6Clo monocytes, was also performed. Brain mapping of CX3CR1GFP/+ and CCR2RFP/+ cells 3 days after MCAo showed absence of CX3CR1GFP/+ Mo/MΦ but accumulation of CCR2RFP/+ Mo/MΦ throughout the ischemic territory. On the other hand, CX3CR1+ cells accumulated 14 days after MCAo at the border of the infarct core where CCR2RFP/+ accrued. Whereas the amoeboid morphology of CCR2RFP/+ Mo/MΦ remained unchanged over time, CX3CR1GFP/+ cells exhibited three distinct phenotypes: amoeboid cells with retracted processes, ramified cells, and perivascular elongated cells. CX3CR1GFP/+ cells were positive for the Mo/MΦ marker Iba1 and phenotypically distinct from endothelial cells, smooth muscle cells, pericytes, neurons, astrocytes, or oligodendrocytes. Because accumulation of CX3CR1+Ly6Clo Mo/MΦ was absent in the brains of CCR2 deficient mice, which exhibit deficiency in CCR2+Ly6Chi Mo/MΦ recruitment, but not in NR4A1-/- chimeric mice, which lack of circulating CX3CR1+Ly6Clo monocytes, our data suggest a local transition of CCR2+Ly6Chi Mo/MΦ into CX3CR1+Ly6Clo Mo/MΦ phenotype. CX3CR1+Ly6Clo arise in the brain parenchyma from CCR2+Ly6Chi Mo/MΦ rather than being de novo recruited from the blood. These findings provide new insights into the trafficking and phenotypic diversity of monocyte subtypes in the post-ischemic brain.


BAli-Phy: simultaneous Bayesian inference of alignment and phylogeny.
BAli-Phy is a Bayesian posterior sampler that employs Markov chain Monte Carlo to explore the joint space of alignment and phylogeny given molecular sequence data. Simultaneous estimation eliminates bias toward inaccurate alignment guide-trees, employs more sophisticated substitution models during alignment and automatically utilizes information in shared insertion/deletions to help infer phylogenies. Software is available for download at http://www.biomath.ucla.edu/msuchard/bali-phy.


End-inspiratory occlusion in the presence of intrinsic PEEP.
Typical modern mechanical ventilators offer the clinician the possibility of automatically performing end-inspiratory occlusion maneuvers. The static conditions induced by such maneuvers are indeed favorable to estimating patient's respiratory mechanics in terms of total resistance (R) and elastance (E). These are parameters of wide clinical interest. However, in the presence of intrinsic PEEP, the standard formula used to compute E via the occlusion maneuver is known to be inaccurate. In this paper we propose an alternative method for the estimation of E via the occlusion maneuver that eliminates the bias by leveraging concepts derived from physiological modeling of the respiratory system dynamics. The proposed method is also capable of accounting for respiratory efforts triggering the breath, and hence can be applied in both passive and spontaneously breathing conditions.


Teleconsulting: a practical account of pitfalls, problems and promise. Experience from the TEAM project group.
In Wales the Tele Education and Medicine (TEAM) project has given clinicians, in both the primary- and secondary-care sectors, practical experience in teleconsulting. From this project we have been able to identify the potential pitfalls and problems in developing and using this new technology. These problems include: using teleconsulting simply because it is fashionable; the failure to base it on the needs of the patients and the primary-care physicians; the failure to validate accuracy, acceptability and cost; the failure to adapt to new technical improvements; and the failure to scale up from a pilot project to a wider teleconsulting service. In our experience technical support is essential and is best facilitated by multisite cooperation, rather than small free-standing projects.


[Thrombosis of a coronary stent after discontinuing treatment with clopidogrel].
A drug-eluting stent was implanted in four patients, a man aged 67 and a woman aged 42 with acute myocardial infarction, a woman aged 41 with unstable angina pectoris and a man aged 41 with stable angina pectoris. All suffered stent thrombosis after discontinuation (in three cases prematurely) of clopidogrel therapy. Reasons for discontinuation included allergic reaction, a dental procedure and refusal of reimbursement by the insurer. In order to restore stent patency they were treated by percutaneous coronary intervention and all patients suffered irreversible myocardial damage. Combination therapy using acetylsalicylic acid and clopidogrel during and after angioplasty for the prevention of long- and short-term complications is necessary. Stent thrombosis after drug-eluting stent implantation usually occurs within 1-4 weeks following discontinuation ofantiplatelet medication. These cases stress the importance of antiplatelet therapy after stent implantation. Physicians, dentists and patients must be aware of the risk of the early discontinuation ofantiplatelet therapy.