Plasma antibodies against heat shock protein 70 correlate with the incidence and severity of asthma in a Chinese population.
The heat shock proteins (Hsps) are induced by stresses such as allergic factors and inflammatory responses in bronchi epithelial cells and therefore may be detectable in patients with asthma. However, the etiologic link between anti-Hsps and asthma (its severity and related inflammatory responses such as interleukin-4 and immunoglobulin E) has not been established. We determined whether antibodies against Hsp60 and Hsp70 were present in patients with asthma and evaluated their associations with risk and severity of asthma. We determined the levels of anti-Hsp60 and anti-Hsp70 by immunoblot and their associations with risk and symptom severity of asthma in 95 patients with asthma and 99 matched non-symptomatic controls using multivariate logistic regression analysis. Compared to the controls, asthma patients were more likely to have detectable anti-Hsp60 (17.2% vs 5.1%) and anti-Hsp70 (33.7% vs 8.1%) (p < or = 0.001). In particular, the presence of anti-Hsp70 was associated with a greater than 2 fold risk for asthma (adjusted OR = 2.21; 95% CI = 1.35 approximately 3.59). Furthermore, both anti-Hsp60 and anti-Hsp70 levels were positively correlated with symptom severity (p < 0.05) as well as interleukin-4 and immunoglobulin E (p < 0.05). Individuals with antibodies against anti-Hsp60 and anti-Hsp70 were more likely to have a family history of asthma (p < 0.001) and higher plasma concentrations of total immunoglobulin E (p = 0.001) and interleukin-4 (p < 0.05) than those without antibodies. These data suggest that anti-Hsp60 and especially anti-Hsp70 correlate with the attacks and severity of asthma. The underlying molecular mechanisms linking antibodies to heat shock proteins and asthma remain to be investigated.


Investigation of Prognostic Features in Primary Cutaneous and Soft Tissue Angiosarcoma After Surgical Resection: A Retrospective Study.
Primary cutaneous and soft tissue angiosarcoma is a rare but highly aggressive malignancy. To date, surgical resection is the mainstay of treatment, but poor prognosis is expected. To investigate whether there are factors associated with poor prognosis after surgical resection and to develop a treatment guideline for current therapy, we retrospectively collected data on 28 patients who underwent surgery as initial treatment and reviewed patient demographics, tumor characteristics, disease courses, and prognoses from September 1996 to May 2013. Of these 28 patients, 17 (60.7%) were men and the mean age at first diagnosis was 66.57 ± 18.57 years. Anatomically, 17 (60.7%) tumors were in the scalp and 11 (39.3%) were in other sites of the body. Of the 28 patients, 23 (82.1%) had achieved negative surgical margins, 24 (85.7%) received adjuvant radiation therapy, and 17 (60.7%) received adjuvant chemotherapy. Twenty-one patients (75%) died during a mean follow-up time of 35.86 ± 28.91 months, and all deaths were caused by angiosarcoma. The 5-year overall survival rate was 17.86%. Sixteen (57.1%) patients had locoregional tumor recurrence, and 20 (71.4%) had distant metastases, with a median of 9.17 (range, 1.9-98.07) months to recurrence or metastasis. Possible predictors of poor prognosis (P < 0.05) in terms of disease-free survival after surgical resection were male sex, cardiovascular disease, smoking, and scalp angiosarcomas, those in terms of overall survival were older than 70 years, male sex, cardiovascular disease, smoking, scalp angiosarcomas, distant metastases, and not receiving adjuvant chemotherapy. In conclusion, although multimodal treatments are used, the overall prognosis after surgical resection is still poor, especially for patients with the above predictive factors. An early diagnosis and complete resection of the primary tumor with or without adjuvant radiotherapy and chemotherapy are suggested for a potential better outcome. For those who have a diffuse lesion pattern with the involvement of vital structures, recurrence, or metastasis, palliative resection could be an alternative treatment choice.


Nutrient utilization in lambs fed diets high in sodium or potassium.
Twenty-four wether lambs averaging 47 kg were used to study the effects of dietary K and Na additions on metabolism of lambs. Lambs were randomly allotted to four treatments and fed 900 g/d of the following: control diet consisting of 50% ground tall fescue hay and 50% concentrate; K diet calculated to contain 4% K with K added as KCl; Na diet calculated to contain 4% Na with Na added as NaCl, and K-Na diet containing 2% K and 2% Na with K and Na added from the same sources as in the K and Na diets. Water intake and urine excretion were highest for lambs fed the Na diet. Dry matter (DM) and crude protein (CP) digestibilities were similar among treatments. The K-Na diet resulted in decreased (P less than .05) acid detergent fiber (ADF) digestibility compared with lambs fed the Na diet. Nitrogen (N) retention was highest (P less than .05) in lambs fed the K diet and lowest in those fed the Na diet. Rumen NH3-N was lower (P less than .05) in lambs fed the Na diet compared with controls. Rumen K at 2 and 6 h postfeeding was highest (P less than .05) and rumen Na at 6 h lowest (P less than .05) for lambs fed the K diet. Plasma K values at both sampling times were highest (P less than .05) in lambs fed the K diet. At 6 h postfeeding, plasma Mg was higher in control lambs compared with those fed the K-Na diet.(ABSTRACT TRUNCATED AT 250 WORDS)


Functional mapping of quantitative trait loci that interact with the hg mutation to regulate growth trajectories in mice.
The high growth (hg) mutation increases body size in mice by 30-50%. Given the complexity of the genetic regulation of animal growth, it is likely that the effect of this major locus is mediated by other quantitative trait loci (QTL) with smaller effects within a web of gene interactions. In this article, we extend our functional mapping model to characterize modifier QTL that interact with the hg locus during ontogenetic growth. Our model is derived within the maximum-likelihood context, incorporated by mathematical aspects of growth laws and implemented with the EM algorithm. In an F2 population founded by a congenic high growth (HG) line and non-HG line, a highly additive effect due to the hg gene was detected on growth trajectories. Three QTL located on chromosomes 2 and X were identified to trigger significant additive and/or dominant effects on the process of growth. The most significant finding made from our model is that these QTL interact with the hg locus to affect the shapes of the growth process. Our model provides a powerful means for understanding the genetic architecture and regulation of growth rate and body size in mammals.


Radioembolization of liver tumors with yttrium-90 microspheres.
Radioembolization (RE), also termed selective internal radiation therapy (SIRT), has been gradually introduced to the clinical arsenal of cytoreductive modalities in recent years. There is growing evidence for efficiency in liver tumors of various entities, with the most prominent ones being hepatocellular carcinoma, colorectal cancer, and neuroendocrine tumors. Hepatic metastases of numerous other tumor entities including breast cancer, cholangiocarcinoma, and pancreatic cancer are treatment-sensitive, even when being refractory to other treatment modalities such as bland-embolization, regional, or systemic chemotherapy. The antitumor effect of SIRT is related to radiation rather than embolization, with extraordinary high local radiation doses obtained selectively at the site of viable tumor and little affection of the surrounding normal liver tissue. Morphologic changes after RE may pose difficulties for interpretation in conventional restaging with regard to tumor viability and true response to treatment. Therefore, functional imaging, that is, metabolic imaging with (18)F fluorodeoxyglucose positron emission tomography (computed tomography) in the majority of treated tumors, is regarded the gold standard in this respect and should be included for pre- and post-SIRT assessment. To prevent serious toxicity to be associated with the potent antitumor efficacy, meticulous pretreatment evaluation is of particular importance. Improvements in predicting dosimetry will help optimize treatment and patient selection. Nuclear medicine procedures are essential for planning, performing, and monitoring of RE. However, the interdisciplinary aspect of patient management has to be emphasized for this particular treatment form. As SIRT is moving forward from the salvage setting indication to the use in earlier stages of hepatic tumor disease and with the advent of new treatment protocols and targeted therapies, embedding SIRT into a multidisciplinary approach will become even more important. This article focuses on procedural and technical aspects for selection, preparation, and performance of treatment as well as post-therapeutic monitoring and response assessment.


How imputation can mitigate SNP ascertainment Bias.
Population genetic studies based on genotyped single nucleotide polymorphisms (SNPs) are influenced by a non-random selection of the SNPs included in the used genotyping arrays. The resulting bias in the estimation of allele frequency spectra and population genetics parameters like heterozygosity and genetic distances relative to whole genome sequencing (WGS) data is known as SNP ascertainment bias. Full correction for this bias requires detailed knowledge of the array design process, which is often not available in practice. This study suggests an alternative approach to mitigate ascertainment bias of a large set of genotyped individuals by using information of a small set of sequenced individuals via imputation without the need for prior knowledge on the array design. The strategy was first tested by simulating additional ascertainment bias with a set of 1566 chickens from 74 populations that were genotyped for the positions of the Affymetrix Axiom™ 580 k Genome-Wide Chicken Array. Imputation accuracy was shown to be consistently higher for populations used for SNP discovery during the simulated array design process. Reference sets of at least one individual per population in the study set led to a strong correction of ascertainment bias for estimates of expected and observed heterozygosity, Wright's Fixation Index and Nei's Standard Genetic Distance. In contrast, unbalanced reference sets (overrepresentation of populations compared to the study set) introduced a new bias towards the reference populations. Finally, the array genotypes were imputed to WGS by utilization of reference sets of 74 individuals (one per population) to 98 individuals (additional commercial chickens) and compared with a mixture of individually and pooled sequenced populations. The imputation reduced the slope between heterozygosity estimates of array data and WGS data from 1.94 to 1.26 when using the smaller balanced reference panel and to 1.44 when using the larger but unbalanced reference panel. This generally supported the results from simulation but was less favorable, advocating for a larger reference panel when imputing to WGS. The results highlight the potential of using imputation for mitigation of SNP ascertainment bias but also underline the need for unbiased reference sets.


General field isolation and the cementation of indirect restorations: Part I.
This article, the first of two parts, has re-introduced the concept of general field isolation. The disadvantages were discussed and recorded as being related to the retention of the slit rubber dam. Innovative techniques which allow for an upgrading of the isolation are introduced through a pictorial essay of five case studies. Further innovations utilising absorbent wafers and cyanoacrylate tissue adhesive are reported in a further five case studies in part 2 of this article scheduled for the August issue.


Loss of DNA minor groove interactions by exonuclease-deficient Klenow polymerase inhibits O6-methylguanine and abasic site translesion synthesis.
The importance of DNA polymerase-DNA minor groove interactions on translesion synthesis (TLS) was examined in vitro using variants of exonuclease-deficient Klenow polymerase and site-specifically modified DNA oligonucleotides. Polymerase variant R668A lacks primer strand interactions, while variant Q849A lacks template strand interactions. O(6)-Methylguanine (m6G) and abasic site TLS was examined in three stages: dNTP insertion opposite the lesion, extension from a terminal lesion-containing base pair, and the dissociation equilibrium of the polymerase from the lesion-containing template. Less than 5% TLS was observed at the insertion step for either variant on the lesion-containing templates. While extensive TLS was observed for WT polymerase on the m6G template, only incorporation opposite the lesion was observed for the R668A variant. Loss of the template strand interaction, Q849A, resulted in the inability to insert dNTPs opposite either the m6G or abasic lesion. For both variants, extension of purine-containing m6G primer-templates was increased relative to WT polymerase. We observed similar extension efficiencies for all variants, relative to WT, using abasic template-primers. Polymerase dissociation/reassociation was studied through the use of a competitor primer/template complex. Dissociation for WT polymerase increased 2-fold and 3-fold, respectively, for m6G and abasic lesion-containing templates, relative to the natural template. Variants lacking DNA minor groove interactions displayed increased dissociation from DNA templates, relative to WT polymerase, but do not display an increased level of lesion-induced polymerase dissociation. Our results indicate that the primer and template strand interactions of the Klenow polymerase with the DNA minor groove are critical for maintaining the DNA-polymerase complex during translesion synthesis.


Ticarcillin/clavulanate in severe infections in patients with varying renal function.
The therapeutic efficacy of ticarcillin/clavulanate was assessed in 71 patients with severe infections: 38 acute pyelonephritis, 16 septicaemia and 19 miscellaneous infections. The patients were classified according to their renal function in: Group A, normal (16 cases); B, mild renal impairment (RI) with creatinine clearance (Clcr) between 80 and 40 ml/min (18 cases); C, moderate RI with Clcr between 40 and 15 ml/min (12 cases); D, severe RI with (Clcr) between 15 and 5 ml/min (13 cases) and E, terminal with (Clcr) less than 5 ml/min (12 cases). A total of 105 microorganisms (48.6% resistant to ticarcillin): 31 Pseudomonas aeruginosa, 18 Escherichia coli, 21 other Enterobacteriaceae, 2 Haemophilus influenzae, 10 Bacteroides spp., 14 enterococci, 8 staphylococci and 1 streptococcus, were isolated. All except six Ps. aeruginosa were sensitive to ticarcillin/clavulanate, using 75:10 microgram discs. Bacteriological eradication was obtained in 97% of the cases on the third day and at the end of treatment, and in 82% of the cases after one month. In all the assessable cases, the clinical symptoms disappeared on the third day except in one patient who developed a resistant strain (Klebsiella oxytoca). The wide range of bacteria assessed and the clinical-bacteriological success rates demonstrated that the ticarcillin/clavulanate combination had an efficacy/safety profile that could be considered excellent. Tolerance was good and side effects were not observed. This study confirms the practical efficacy of the recommended dosages derived from our previous kinetic studies in RI.


Molecular dynamics study of small PNA molecules in lipid-water system.
We present the results of molecular dynamics simulations of small peptide nucleic acid (PNA) molecules, synthetic analogs of DNA, at a lipid bilayer in water. At neutral pH, without any salt, and in the NP(n)gammaT ensemble, two similar PNA molecules (6-mers) with the same nucleic base sequence and different terminal groups are investigated at the interface between water and a 1-palmitoyl-2-oleoylphosphatidylcholine lipid bilayer. The results of our simulations suggest that at low ionic strength of the solution, both PNA molecules adsorb at the lipid-water interface. In the case where the PNA molecule has charged terminal groups, the main driving force of adsorption is the electrostatic attraction between the charged groups of PNA and the lipid heads. The main driving force of adsorption of the PNA molecule with neutral terminal groups is the hydrophobic interaction of the nonpolar groups. Our simulations suggest that the system free energy change associated with PNA adsorption at the lipid-water interface is on the order of several tens of kT per PNA molecule in both cases.


Sensitization of multidrug-resistant mouse ascites HD33 and Chinese hamster ovary CHRC5S3 cells by a photoreactive vinblastine derivative, NAPAVIN.
We have synthesized a new photoreactive vinblastine derivative, 3-[[[2-amino(4-azido-2-nitrophenyl)ethyl]amino] carbonyl]-O4-deacetyl-3-de-(methoxycarbonyl)-vincaleukoblastine (NAPAVIN), which absorbs light at around 450 nm. We report here its effects in vitro on multidrug-resistant mouse HD33 Ehrlich-Lettré ascites cells, on Chinese hamster ovary CHRC5S3 cells, on the corresponding drug-sensitive cells, on chemosensitive rat TMA1 mammary carcinoma, and on human SW48 colon carcinoma cells. Cells were incubated with the drug prior to activation by laser light at 457 nm. In Vinca alkaloid-sensitive cells, the short-term effects (30 to 72 h after treatment) of NAPAVIN with and without irradiation on cell proliferation are comparable to those of vinblastine. In drug-resistant cells, NAPAVIN without irradiation reduces the 50% inhibitory concentration 2- to 9-fold, compared with vinblastine. Upon irradiation with an argon laser at 457 nm, the concentration causing 50% inhibition of cell proliferation is further decreased to a total of 9- to 33-fold. Long-term effects (up to 6 wk after treatment) are seen in both sensitive and resistant cells. A single dose of the photoactivated drug causes a 6- to 9-fold larger delay (5 wk) in proliferation, compared with an equal dose of vinblastine.


Urodynamic impact of acute urinary retention in patients with benign prostatic hyperplasia: a 2-year follow-up after transurethral resection of the prostate.
Benign prostatic hyperplasia (BPH) may ultimately result in acute urinary retention (AUR). This study was performed to assess the impact of transurethral resection of the prostate (TURP) on urodynamic parameters in patients with BPH using pre- and postoperative pressure-flow studies (PFS) and compare those between patients with and without preoperative AUR. 78 patients underwent TURP because of symptoms due to BPH and were evaluated preoperatively and at follow-up after a mean ± SD of 27 ± 11.5 months by the International Prostate Symptom Score and PFS. 32% of patients were admitted with AUR. The clinical and principal urodynamic parameters exhibited statistically significant improvement reaching normal values after TURP in most patients. Comparing patients with and without AUR, the bladder compliance significantly increased (p = 0.0013) from the preoperative period to follow-up only in patients with preoperative AUR. The minimal opening pressure decreased significantly more (p = 0.0077) from the preoperative period to follow-up in the non-AUR group. Patients older than 80 years and younger patients showed comparable results. TURP leads to a sustained and age-independent improvement of clinically relevant PFS parameters in patients with BPH. Patients with preoperative AUR had comparable symptomatic, but an impaired urodynamic outcome compared to patients without AUR.


Genetic variability and population structure of the Montezuma quail (Cyrtonyx montezumae) in the northern limit of its distribution.
Restricted movement among populations decreases genetic variation, which may be the case for the Montezuma quail (Cyrtonyx montezumae), a small game bird that rarely flies long distances. In the northern limit of its distribution, it inhabits oak-juniper-pine savannas of Arizona, New Mexico, and Texas. Understanding genetic structure can provide information about the demographic history of populations that is also important for conservation and management. The objective of this study was to determine patterns of genetic variation in Montezuma quail populations using nine DNA microsatellite loci. We genotyped 119 individuals from four study populations: Arizona, Western New Mexico, Central New Mexico, and West Texas. Compared to other quail, heterozygosity was low (H¯0 = 0.22 ± 0.04) and there were fewer alleles per locus (Ā = 2.41 ± 0.27). The global population genetic differentiation index RST = 0.045 suggests little genetic structure, even though a Bayesian allocation analysis suggested three genetic clusters (K = 3). This analysis also suggested admixture between clusters. Nevertheless, an isolation-by-distance analysis indicates a strong correlation (r = 0.937) and moderate evidence (P = 0.032) of non-independence between geographical and genetic distances. Climate change projections indicate an increase in aridity for this region, especially in temperate ecosystems where the species occurs. In this scenario, corridors between the populations may disappear, thus causing their complete isolation.


The fan effect in fMRI: left hemisphere specialization in verbal working memory.
We studied the fan effect of verbal working memory using functional magnetic resonance imaging (fMRI). Participants were presented with a sentence-pair matching task that described semantic relationships (e.g. classroom-school). Working memory load and semantic processing were manipulated by increasing the number of sentences to be remembered and varying whether they matched expectation. Increased working memory load elicited activation in left dorsal frontal and left inferior parietal regions, and also delayed the hemodynamic responses. Convergent results from semantic matches occurred in the left parietal lobe, whereas, left ventral frontal activation from mismatches diverged from working memory results. The findings were consistent with behavioural and electrophysiological evidence, with the fan effect in fMRI providing novel insight into the spatiotemporal nature of verbal working memory in the left hemisphere.


Relationship between increased airway responsiveness and asthma severity in the childhood asthma management program.
The relationship between increased airway responsiveness and asthma severity in children is unclear. The Childhood Asthma Management Program (CAMP) with 1,041 children with mild to moderate asthma offers an opportunity to relate the concentration of methacholine that causes a 20% fall in FEV(1) (PC(20)) to level of lung function, occurrence of respiratory symptoms, duration of disease, and assessment of severity by clinical staff. Decreasing PC(20) was found to be associated with lower levels of lung function (prebronchodilator percent predicted FEV(1): r = 0.29, beta = 3.5, p < 0.001), the occurrence of chronic asthma symptoms, persistent wheezing (odds ratio [OR] = 1.66, p < 0.001), subjective clinical staff assessment of asthma severity (p < 0.001), and longer duration of asthma (r = -0.11, beta = -0.20, p < 0.002). These data provide evidence that the degree of airway responsiveness is linked to disease severity in children with mild to moderate asthma.


Binary classification of chalcone derivatives with LDA or KNN based on their antileishmanial activity and molecular descriptors selected using the Successive Projections Algorithm feature-selection technique.
Chalcones are naturally occurring aromatic ketones, which consist of an α-, β-unsaturated carbonyl system joining two aryl rings. These compounds are reported to exhibit several pharmacological activities, including antiparasitic, antibacterial, antifungal, anticancer, immunomodulatory, nitric oxide inhibition and anti-inflammatory effects. In the present work, a Quantitative Structure-Activity Relationship (QSAR) study is carried out to classify chalcone derivatives with respect to their antileishmanial activity (active/inactive) on the basis of molecular descriptors. For this purpose, two techniques to select descriptors are employed, the Successive Projections Algorithm (SPA) and the Genetic Algorithm (GA). The selected descriptors are initially employed to build Linear Discriminant Analysis (LDA) models. An additional investigation is then carried out to determine whether the results can be improved by using a non-parametric classification technique (One Nearest Neighbour, 1NN). In a case study involving 100 chalcone derivatives, the 1NN models were found to provide better rates of correct classification than LDA, both in the training and test sets. The best result was achieved by a SPA-1NN model with six molecular descriptors, which provided correct classification rates of 97% and 84% for the training and test sets, respectively.


Protective effect of apocynin against gentamicin-induced nephrotoxicity in rats.
Gentamicin (GNT) is an aminoglycoside antibiotic used for treatment of serious infections, and the nephrotoxic adverse effect is one of the main therapeutic limitations. This study aimed to investigate the possible protective effect of apocynin (APO) on nephrotoxicity induced by GNT in rats. Twenty-four rats were allocated into three groups: control, GNT (100 mg/kg, intraperitoneally (i.p.)), and GNT plus APO (10 mg/kg, i.p.). All rats were killed at the end of the experiment, and then the blood, urine, and kidneys samples were taken. GNT-induced nephrotoxicity was manifested by a significant ( p < 0.05) increase in the weight of kidney, 24-h urine volume, renal somatic index (RSI), protein in urine, serum lactate dehydrogenase (LDH), creatinine (Cr), blood urea nitrogen (BUN), renal Fas ligand (CD95), nitric oxide (NO), and malondialdehyde (MDA). Furthermore, a significant reduction in body weight, creatinine clearance (CCr), serum albumin, renal superoxide dismutase (SOD), and glutathione activities were detected when compared with the control rats. APO ameliorated the nephrotoxic effect and oxidative damage caused by GNT by improving tissue morphology and significantly decreasing 24-h urine volume, RSI, serum Cr, LDH and BUN, protein in urine, and renal content of MDA, CD95, and NO. Additionally, APO caused a significant elevation in renal SOD activity and CCr when compared with the GNT group. These results confirm that APO by its anti-inflammatory, antiapoptotic, and antioxidant effects can ameliorate GNT-induced nephrotoxicity.


Images: A Case of EEG Artifact By Proxy.
In this manuscript we describe a case of electroencephalography artifact during polysomnography that occurred in the context of mother co-sleeping with her child. The potential interference from a co-sleeping parent's electrocardiography, as illustrated in this case, may be an under-recognized source of electroencephalography artifact in pediatric patients. Li A, Matthews CK, Plante DT. A case of EEG artifact by proxy. J Clin Sleep Med. 2019;15(9):1385-1387.


Reduced nitric oxide synthase in the brainstem contributes to enhanced sympathetic drive in rats with heart failure.
Recent studies have suggested that central nervous mechanisms are involved in the enhanced sympathetic drive observed in heart failure (HF). Nitric oxide (NO) in the brainstem has been shown to reduce sympathetic nerve activity. The aim of this study was to determine whether the expression of neuronal nitric oxide synthase (nNOS) in the brainstem is reduced in rats with HF. Heart failure was produced by myocardial infarction in Wistar-Kyoto rats (HF group). Hemodynamic and echocardiographic examinations were performed. Western blot analysis for nNOS in the nucleus tractus solitarii (NTS) and the rostral ventrolateral medulla (RVLM) in the brainstem were performed to determine the expression of the nNOS gene in the HF group or sham-operated (control) group. We also performed in situ hybridization for nNOS mRNA and distribution in the brainstem. The expression of nNOS protein in the NTS and the RVLM were reduced in the HF group compared to the control group. The expression of nNOS mRNA in the brainstem was also reduced in the HF group, particularly in the NTS, compared to the control group. Intracisternal injection of NG-monomethyl-L-arginine elicited a smaller pressor response in the HF group than in the control group. These results suggest that reduced nNOS expression in the NTS and the RVLM, and the resulting reduced NO production of these sites, contribute to the enhanced sympathetic drive in HF.


Species richness in natural and disturbed habitats: Asteraceae and Flower-head insects (Tephritidae: Diptera).
Anthropogenic changes in the landscape result in an environmental mosaic with serious consequences for biodiversity. The aim of the present study was to assess the effects of the anthropogenic changes on Asteraceae richness and abundance, and to evaluate the consequences for the richness of Tephritidae assemblages in five sampling sites, with three sampled habitats in each: cerrado (Brazilian savanna), eucalyptus stands and pasture. Sampling was carried out in 15 random transects (cerrados and one pasture) and in 30 transects (eucalyptus stands and the remaining pastures). Composition, species richness and insect abundance in each habitat type was estimated by sampling the flower heads for each species of host plant, collected by four people for 1h. Differences in mean abundance of plant population between habitats and sites were tested by two-way ANOVA. Differences in plant species richness between habitats and sites and effects of habitat, site and host plant richness on insect richness were tested using a generalized linear model with Poisson errors. Within each sampling site, cerrados showed higher species richness of Asteraceae than pastures and eucalyptus stands. There were also significant differences in plant richness among sites. Mean population abundance values were significantly different among habitats, but not among sites. Increased host plant richness led to significant insect species richness. There were no additional significant effects of habitat on insect richness. Therefore, anthropogenic alterations in landscape determined the impoverishment of plant assemblages and therefore of insect assemblages, because of the positive relationship between host plant richness and insect richness.


Experimental evidence of an x-ray laser.
A three-stage neodymium:glass laser has been used to produce collimated x-radiation from an aqueous copper(II) sulfate gel. The 1.06-mum Q-switch pulse from the neodymium laser was focused by a cylindrical lens to a horizontal line traversing a microscope slide sandwich that contained a thin film of gel. The emission from the gel was detected as a 0.2-mm spot on shielded, standard x-ray photographic film at distances that varied from 30 to 110 cm from the sandwich. Spot size did not increase with distance, suggesting coherence of the x-rays.


Managing health disasters and Civil-Military Cooperation: A case of COVID-19 in Pakistan.
As an institution, the Pakistan Army has been playing a significant role in dealing with emergencies and disasters facing the nation. The novel coronavirus disease, Severe Acute Respiratory Syndrome (SARS) COVID-19, was wreaking havoc around the world. The pandemic is a threat to health and has caused severe damage across most aspects of the society. The situation forced the formation of a unique series of civil-military inter-agency relationships to be formed, in order to curb the spread of the pandemic. The Pakistan Army that was neither trained nor equipped to undertake any such health disaster management operation played a significant role in preventing disease and overcoming the disaster. Civil-military cooperation (CIMIC) was the key to the successful response of Pakistan towards COVID-19. The research was based on qualitative interviews that analysed the phenomenon of COVID-19 pandemic, that is, 'health disaster', to elucidate the disaster management practices performed through the framework of CIMIC in Pakistan. With regard to this, the article argued that formulating a comprehensive guideline or framework was necessary to maintain an effective and cooperative relationship between civil and military components. It further demonstrated the need to recognise the constitutive factors that influenced the functionalisation and institutionalisation of CIMIC to manage the highly complex health-related emergencies.


[Iron in pre-operative stage and transfusion in patients undergoing hysterectomy].
The correction of preoperative anemia is part of the patient blood management program, in order to improve the patient's clinical results by reducing the number of transfusions in surgery. Uterine fibroids can cause anemia, so the application of iron before hysterectomy could reduce transfusion. To evaluate the impact of iron treatment in the preoperative stage on the need for transfusion in patients with anemia secondary to myomatosis in the trans and postoperative stage of hysterectomy. Patients with uterine myomatosis who presented with microcytic anemia in the preoperative stage were included; clinical records were reviewed, the clinical characteristics of the population were obtained; The patients were distributed into two study groups according to whether or not they had received iron treatment; the outcome variable was the transfusion of packed erythrocytes in the first 7 days after surgery. 134 patients were included, with a median fibroid size of 4 cm. 21 (15.6%) patients used iron. Patients who used iron had a relative risk (RR): 0.36 (95%CI: 0.12-1.07). Delta hemoglobin < 1 g/dL, RR: 1.59 (95%CI: 0.94-2.67). Uterine fibroid size > 5cm had a RR of 1.96 (95%CI: 1.25-3.05). Treatment with iron in the pre-surgical stage showed a tendency to protect transfusions in the trans and post-surgical stage. The main factor related to transfusion was fibroid size > 5 cm.


Extracellular ATP a New Player in Cancer Metabolism: NSCLC Cells Internalize ATP In Vitro and In Vivo Using Multiple Endocytic Mechanisms.
Intratumoral extracellular ATP concentrations are 1000 times higher than those in normal tissues of the same cell origin. However, whether or not cancer cells use the abundant extracellular ATP was unknown until we recently reported that cancer cells internalize ATP. The internalized ATP was found to substantially increase intracellular ATP concentration and promote cell proliferation and drug resistance in cancer cells. Here, using a nonhydrolyzable fluorescent ATP (NHF-ATP), radioactive and regular ATP, coupled with high and low molecular weight dextrans as endocytosis tracers and fluorescence microscopy and ATP assays, cultured human NSCLC A549 and H1299 cells as well as A549 tumor xenografts were found to internalize extracellular ATP at concentrations within the reported intratumoral extracellular ATP concentration range. In addition to macropinocytosis, both clathrin- and caveolae-mediated endocytosis significantly contribute to the ATP internalization, which led to an approximately 30% (within 45 minutes) or more than 50% (within 4 hours) increase in intracellular ATP levels after ATP incubation. This increase could not be accounted for by either purinergic receptor signaling or increased intracellular ATP synthesis rates in the ATP-treated cancer cells. These new findings significantly deepen our understanding of the Warburg effect by shedding light on how cancer cells in tumors, which are heterogeneous for oxygen and nutrition supplies, take up extracellular ATP and use the internalized ATP to perform multiple previously unrecognized functions of biological importance. They strongly suggest the existence of ATP sharing among cancer and stromal cells in tumors and simultaneously identify multiple new anticancer targets. Extracellular ATP is taken up by human lung cancer cells and tumors via macropinocytosis and other endocytic processes to supplement their extra energy needs for cancer growth, survival, and drug resistance, thus providing novel targets for future cancer therapy. Mol Cancer Res; 14(11); 1087-96. ©2016 AACR.


Scanning electron microscopy of the human myocardium.
Owing to the impossibility of fixation, in the human being, by means of perfusion in vivo and the rare availability of fresh comparatively intact hearts resected at transplantation, the possibility was explored of using post-mortem material in instances where the autopsies were performed within 2 hours of demise of the patients. Four cases were examined: 2 normal adult hearts and 2 hearts of hypertensive patients in the stage of decompensation. The hearts were fixed by means of perfusion with 2.5% glutaraldehyde in phosphate buffer, pH 7.4. Contiguous blocks were taken for light microscopy (LM) and scanning electron microscopy (SEM) from the left ventricular free wall of all 4 cases and of the impulse conducting system of the heart in the 2 normal hearts. The SEM material was processed by the osmium-thiocarbohydrazide-osmium method (O-T-O). There was good correlation between the LM and SEM findings. The left ventricular blocks were sectioned in the transverse axis and SEM showed a step-wise transection of the myofibrils. Z and M bands, mitochondria and myofilaments were identified a ultrastructural magnifications. The difference in vascularity between normal and hypertensive myocardium and the presence of para-arterial fibrosis in the latter were demonstrated by SEM. The SEM study of the impulse conducting system of the heart included the sinoatrial (SA) and atrioventricular (AV) nodes and the penetrating portion of the atrioventricular (AV) bundle of His. Characteristic pacemaker or "P" cells were identified in the nodes.


Can an aircraft be piloted via sonification with an acceptable attentional cost? A comparison of blind and sighted pilots.
In the aeronautics field, some authors have suggested that an aircraft's attitude sonification could be used by pilots to cope with spatial disorientation situations. Such a system is currently used by blind pilots to control the attitude of their aircraft. However, given the suspected higher auditory attentional capacities of blind people, the possibility for sighted individuals to use this system remains an open question. For example, its introduction may overload the auditory channel, which may in turn alter the responsiveness of pilots to infrequent but critical auditory warnings. In this study, two groups of pilots (blind versus sighted) performed a simulated flight experiment consisting of successive aircraft maneuvers, on the sole basis of an aircraft sonification. Maneuver difficulty was varied while we assessed flight performance along with subjective and electroencephalographic (EEG) measures of workload. The results showed that both groups of participants reached target-attitudes with a good accuracy. However, more complex maneuvers increased subjective workload and impaired brain responsiveness toward unexpected auditory stimuli as demonstrated by lower N1 and P3 amplitudes. Despite that the EEG signal showed a clear reorganization of the brain in the blind participants (higher alpha power), the brain responsiveness to unexpected auditory stimuli was not significantly different between the two groups. The results suggest that an auditory display might provide useful additional information to spatially disoriented pilots with normal vision. However, its use should be restricted to critical situations and simple recovery or guidance maneuvers.


Characterization of the mutational profile of 11 diffuse large B-cell lymphoma cell lines.
Investigation of cancer cell lines is important for oncology research to characterize and understand mechanisms of cellular signaling and survival strategies in cancer. We analyzed the mutational profile of 11 diffuse large B-cell lymphoma (DLBCL) cell lines using a customized high throughput sequencing panel. We compared our data to previously published mutation data to better characterize these cell lines and establish consensus on the mutational status of some functionally relevant genes. With our targeted sequencing approach we detected 61 somatic mutations. The most frequently affected gene was TP53. MYD88 mutations were only seen in activated B-cell like cell lines. Overall comparison across different datasets revealed that just around 38% of mutations are reliable and can be validated by at least two independent observations whereas 24% of mutations could not be validated. Our analysis reveals considerable discrepancies regarding the mutational profile of some well-established cell lines.


A comparison of routine culture with polymerase chain reaction technology for the detection of Mycoplasma species in feline nasal samples.
Nasal flush samples were collected from 20 cats and submitted for Mycoplasma culture and polymerase chain reaction (PCR). Nasal biopsy samples were also obtained from each cat and simultaneously evaluated for Mycoplasma by standard culture and PCR. Concordance of the test results was determined through calculation of the kappa statistic. In 6 cats, nasal flush samples were culture positive for Mycoplasma. PCR was positive in each culture-positive cat and also positive in 1 flush sample that was culture negative. DNA sequencing of the PCR product from the culture negative flush sample identified the organism as Mycoplasma arginini. All other flush samples that were culture negative were also PCR negative (kappa = 0.89). Nasal biopsy samples from 7 cats were culture positive for Mycoplasma, and all were PCR positive. Biopsy samples that were culture negative for Mycoplasma were also PCR negative (kappa = 1.0). Results of culture and PCR for both nasal flush and biopsy were concordant in 19 of 20 cats, and PCR was able to identify an unusual Mycoplasma species that did not grow in culture. In most cats, organisms could be detected in either nasal flush or biopsy samples. In this study, PCR provided rapid and sensitive detection of Mycoplasma species in nasal samples from cats and detected 1 organism that did not grow in culture.


Medial instability of the elbow in throwing athletes. Treatment by repair or reconstruction of the ulnar collateral ligament.
From September 1974 to December 1987, seventy-one patients were operated on for valgus instability of the elbow. The average length of follow-up of sixty-eight patients (seventy operations) was 6.3 years (range, two to fifteen years). At the operation, a torn or incompetent ulnar collateral ligament was found. Fourteen patients had a direct repair of the ligament, and fifty-six had a reconstruction of the ligament using a free tendon graft. The result was excellent or good in ten patients in the repair group and in forty-five (80 per cent) in the reconstruction group. Seven of the fourteen patients who had a direct repair returned to the previous level of participation in their sport. Of the fifty-six who had a reconstruction, thirty-eight (68 per cent) returned to the previous level of participation. Twelve of the sixteen major-league baseball players who had a reconstruction as the primary operation (no previous operation on the elbow) were able to return to playing major-league baseball, and two of the seven major-league players who had a direct repair returned to playing major-league baseball. Previous operations on the elbow decreased the chance of returning to the previous level of sports participation (p = 0.04). Fifteen patients had postoperative ulnar neuropathy. This was transient in six patients, only one of whom was unable to return to the previous level of sport. The other nine patients had an additional operation for the neuropathy; four were able to return to the previous level of sport.


Association between language, serious adverse events, and length of stay among hospitalized children.
To evaluate the risk for serious/sentinel adverse events among hospitalized children according to race, ethnicity, and language and to evaluate factors affecting length of stay associated with serious/sentinel adverse events. We conducted a retrospective cohort study of all pediatric inpatients at a large children's hospital from October 2007 to October 2009. We evaluated the relationship between self-reported race, ethnicity, and primary language; with having a serious or sentinel adverse event, defined as an unexpected occurrence involving risk of death or serious injury; or a potentially harmful event resulting from nonstandard practice. We also examined length of stay. Clinical complexity was adjusted for by using Clinical Risk Groups. Of 33885 patients, 8% spoke Spanish and 4% spoke other languages. Serious and sentinel events were rare; however, among patients with such events, 14% spoke Spanish. Adjusting for potential confounders, Spanish speakers trended toward an elevated odds of adverse event (odds ratio: 1.83 [95% confidence interval: 0.98-3.39]). Controlling for age, language, and clinical complexity, having an adverse event was associated with a nearly fivefold increase in length of stay (95% confidence interval: 3.87-6.12). Spanish-speaking patients with an adverse event were hospitalized significantly longer than comparable English speakers (26 vs 12.7 days; P = .03 for interaction between language and adverse event). Hospitalized children from Spanish-speaking families had significantly longer hospital stays in association with an adverse event and may have increased odds of a serious or sentinel event. These findings suggest that an important component of patient safety may be to address communication barriers.


Biophysical and molecular characterization of a novel de novo KCNJ2 mutation associated with Andersen-Tawil syndrome and catecholaminergic polymorphic ventricular tachycardia mimicry.
Mutations in KCNJ2, the gene encoding the human inward rectifier potassium channel Kir2.1 (IK1 or IKir2.1), have been identified in Andersen-Tawil syndrome. Andersen-Tawil syndrome is a multisystem inherited disease exhibiting periodic paralysis, cardiac arrhythmias, and dysmorphic features at times mimicking catecholaminergic polymorphic ventricular tachycardia. Our proband displayed dysmorphic features including micrognathia, clinodactyly, and syndactyly and exhibited multiform extrasystoles and bidirectional ventricular tachycardia both at rest and during exercise testing. The patient's symptoms continued after administration of nadolol but subsided after treatment with flecainide. Molecular genetic screening revealed a novel heterozygous mutation (c.779G>C/p.R260P) in KCNJ2. Whole-cell patch-clamp studies conducted in TSA201 cells transfected with wild-type human KCNJ2 cDNA (WT-KCNJ2) yielded robust IKir2.1 but no measurable current in cells expressing the R260P mutant. Coexpression of WT and R260P-KCNJ2 (heterozygous expression) yielded a markedly reduced inward IKir2.1 compared with WT alone (-36.5±9.8 pA/pF versus -143.5±11.4 pA/pF, n=8 for both, P<0.001, respectively, at -90 mV), indicating a strong dominant negative effect of the mutant. The outward component of IKir2.1 measured at -50 mV was also markedly reduced with the heterozygous expression versus WT (0.52±5.5 pA/pF versus 23.4±6.7 pA/pF, n=8 for both, P<0.001, respectively). Immunocytochemical analysis indicates that impaired trafficking of R260P-KCNJ2 channels. We report a novel de novo KCNJ2 mutation associated with classic phenotypic features of Andersen-Tawil syndrome and catecholaminergic polymorphic ventricular tachycardia mimicry. The R260P mutation produces a strong dominant negative effect leading to marked suppression of IK1 secondary to a trafficking defect.


A new look at cognitive functioning in pediatric MS.
Cognitive involvement in pediatric multiple sclerosis (MS) relative to adult MS is less defined. This study advances our understanding by measuring cognitive performances in pediatric MS, adult MS, and pediatric healthy controls. Consecutive relapsing pediatric MS participants from the United States Network of Pediatric MS Centers were compared with pediatric healthy controls and adults with relapsing MS. Participants were compared on two screening batteries: the Brief International Cognitive Assessment for MS and the Cogstate Brief Battery. Results were transformed to age-normative z scores. The pediatric groups (MS vs. Healthy Controls) did not differ on either battery's composite mean score or individual test scores (ps > 0.32), nor in the proportions impaired on either battery, Brief International Cognitive Assessment for MS (26% vs. 24%, p = 0.83); Cogstate Brief Battery (26% vs. 32%, p = 0.41). The pediatric versus adult MS group even after controlling for differences in disease duration performed better on the Brief International Cognition Assessment for MS composite (p = 0.03), Symbol Digit Modalities Test (p = 0.02), Rey Auditory Verbal Learning Test (p = 0.01), and Cogstate choice reaction time (p < 0.001). Pediatric MS patients do not differ from healthy pediatric controls on cognitive screens but perform better than adults with MS.


Applying a Behavioral Model Framework for Disaster Recovery Research in Local Public Health Agencies: A Conceptual Approach.
The local public health agency (LPHA) workforce is at the center of the public health emergency preparedness system and is integral to locally driven disaster recovery efforts. Throughout the disaster recovery period, LPHAs have a primary responsibility for community health and are responsible for a large number of health services. In the face of decreasing preparedness funding and increasing frequency and severity of disasters, LPHAs continue to provide essential disaster life cycle services to their communities. However, little is known about the confidence that LPHA workers have in performing disaster recovery-related duties. To date, there is no widely used instrument to measure LPHA workers' sense of efficacy, nor is there an educational intervention designed specifically to bolster disaster recovery-phase efficacy perceptions. Here, we describe the important role of the LPHA workforce in disaster recovery and the operational- and efficacy-related research gaps inherent in today's disaster recovery practices. We then propose a behavioral framework that can be used to examine LPHA workers' disaster recovery perceptions and suggest a research agenda to enhance LPHA workforce disaster recovery efficacy through an evidence-informed educational intervention.


Outcome of patients with sarcoidosis refractory to TNF antagonists: a case series.
Background: Tumor necrosis factor (TNF) antagonists have been reported as an efficient third-line therapy for sarcoidosis but there is no data regarding patients who do not respond to this treatment. Objective: To report the characteristics, the outcome and the response to therapy of patients with sarcoidosis resistant to TNF antagonists. Methods: Patients from the French STAT (Sarcoidosis Treatment with Anti-TNF) registry who were classified as non-responders and who were followed-up for >1 year were included. The response to further therapies was classified as complete response, or partial response, and the others were classified as non-responders. Results: Among the 132 patients from the registry, 14 were considered as non-responders to anti-TNF. Nine patients (66% of women; mean age 48 years) were analyzed. The mean number of organs involved was 4.2. Seven patients were previously treated with more than 2 immunosuppressive treatments. The mean duration of the anti-TNF treatment was 9 months (range, 3-24). After a mean follow-up duration of 58 months (median, 35; range, 19-128) a complete response was observed in 2/9 cases, a partial response in 5/9 cases, and 2/9 cases were considered as non-responders. In all but one patient, the immunosuppressant that allowed the clinical response had previously been used. Furthermore, the dosage was not necessarily increased to gain efficacy. Non-responders were treated by corticosteroids only because of their comorbidities or noncompliance. Conclusion: In patients who do not respond to TNF antagonists, previously used immunosuppressants may be useful. Excluding a differential diagnosis, assessing compliance and testing for anti-drug antibodies should be systematic. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 371-375).


Obtaining an immunoaffinity monolithic material: poly(GMA-co-EDMA) functionalized with an HPV-derived peptide using a thiol-maleimide reaction.
Metabolites have great potential for the design of biomarkers, since their presence or absence provides valuable information about a biological system. In this context, polyclonal antibodies are important metabolites for diagnostic procedures, but in some pathologies, it has been found that these metabolites are present at low concentrations, so it could be difficult to detect them. In this investigation, an organic monolithic material of poly(GMA-co-EDMA) was functionalized with a peptide via Michael addition (thiol-maleimide) click chemistry. The peptide, covalently bound to the monolith, contains the SPINNTKPHEAR sequence derived from the human papilloma virus L1 protein. It was determined that the obtained monolithic support allows selectively isolating polyclonal antibodies against the SPINNTKPHEAR sequence, since they are retained on the chemical surface of the material by an immunoaffinity interaction. The monolithic material functionalization protocol reported here could be applied to incorporate any peptide with a terminal cysteine in order to recover a specific analyte. A new method was developed for isolating and pre-concentrating antibodies using monolithic materials, which could contribute to the improvement of disease detection strategies based on immunoaffinity interactions.


[Pathologic-anatomic reflections on portal hypertension (author's transl)].
Portal hypertension is defined as an increase of the portal venous pressure over 20 cm H2O or 7 mm Hg, respectively. It may be induced by different types of portal venous stenosis or obstruction, primarily by cirrhosis and fibrosis of the liver and, less frequent by posthepatic disorders such as the Budd-Chiari-syndrome or congestive heart failure. Portal hypertension is followed by ectasia and phlebosclerosis of the portal vein, by splenomegaly, ascites and by various types of collateral circulation. Among these, oesophageal varices, are most important since they often lead to acute upper gastrointestinal haemorrhage, the major complication of portal hypertension. Bleeding from oesophaeal varices is essentially based on atrophy of the squamous epithelium, caused by ischemia from local hypoxia and venous stasis. Portal hypertension and the frequently compromised blood clotting mechanism due to reduced synthesis of clotting factors in the liver aggravate the bleeding. Atrophy of the esophageal mucosa presents an area of decreased resistance likely to ulcerate with easy erosion of the varices--usually lying very superficially--; with mechanical irritation by food or peptic erosion from gastroesophageal reflux being frequent inducers of hemorrhage.


Diabetes and psychiatric illness in the total population of Stockholm.
Concomitant psychiatric disorders in people with diabetes affect morbidity and mortality. We aimed to study psychiatric morbidity in people with diabetes and the general population using administrative health care data in Stockholm County. The study population included all living persons who resided in Stockholm County, Sweden, on January 1, 2011 (N=2,058,408). Subjects with a diagnosis of diabetes were identified with data from all consultations in primary health care, specialist outpatient care and inpatient care during the time span 2009-2013. As outcome, information was obtained on all consultations due to any psychiatric diagnosis as well as, specifically, schizophrenia, bipolar disorders, depression, and anxiety disorders, in 2011-2013. Analyses were performed by age group and gender. Age-adjusted odds ratios (ORs) with 95% confidence intervals (95% CI) for women and men with diabetes, using individuals without diabetes as referents, were calculated. Age-adjusted OR for all psychiatric diagnoses among people with diabetes was 1.296 (95% CI 1.267-1.326) for women and 1.399 (95% CI 1.368-1.432) for men. The greatest excess risk was found for schizophrenia, with OR 3.439 (95% CI 3.057-3.868) in women and 2.787 (95% CI 2.514-3.089) in men, with ORs between 1.276 (95% CI 1.227-1.327) and 1.714 (95% CI 1.540-1.905) for the remaining diagnoses. The prevalence of psychiatric disorders is elevated in people with diabetes, which calls for preventive action to be taken to minimize suffering and costs to society.


Hyperammonemic coma after craniotomy: Hepatic encephalopathy from upper gastrointestinal hemorrhage or valproate side effect?: Case report and literature review.
Postoperative coma is not uncommon in patients after craniotomy. It generally presents as mental state changes and is usually caused by intracranial hematoma, brain edema, or swelling. Hyperammonemia can also result in postoperative coma; however, it is rarely recognized as a potential cause in coma patients. Hyperammonemic coma is determined through a complicated differential diagnosis, and although it can also be induced as a side effect of valproate (VPA), this cause is frequently unrecognized or confused with upper gastrointestinal hemorrhage (UGH)-induced hepatic encephalopathy. We herein present a case of valproate-induced hyperammonemic encephalopathy (VHE) to illustrate the rarity of such cases and emphasize the importance of correct diagnosis and proper treatment. A 61-year-old woman with meningioma was admitted into our hospital. Radical resection of the tumor was performed, and the patient recovered well as expected. After administration of valproate for 7 days, the patient was suddenly found in a deep coma, and her mental state deteriorated rapidly. The diagnoses of hepatic encephalopathy was confirmed. However, whether it origins from upper gastrointestinal hemorrhage or valproate side effect is uncertain. The patient's condition fluctuated without improvement during the subsequent 3 days under the treatment of reducing ammonia. With the discontinuation of valproate treatment, the patient regained complete consciousness within 48 hours, and her blood ammonia decreased to the normal range within 4 days. VHE is a rare but serious complication in patients after craniotomy and is diagnosed by mental state changes and elevated blood ammonia. Thus, the regular perioperative administration of VPA, which is frequently neglected as a cause of VHE, should be emphasized. In addition, excluding UGH prior to providing a diagnosis and immediately discontinuing VPA administration are recommended.


Cutting edge: expression of TNFR2 defines a maximally suppressive subset of mouse CD4+CD25+FoxP3+ T regulatory cells: applicability to tumor-infiltrating T regulatory cells.
TNFR2 is predominantly expressed by a subset of human and mouse CD4(+)CD25(+)FoxP3(+) T regulatory cells (Tregs). In this study, we characterized the phenotype and function of TNFR2(+) Tregs in peripheral lymphoid tissues of normal and tumor-bearing C57BL/6 mice. We found that TNFR2 was expressed on 30-40% of the Tregs of the peripheral activated/memory subset that were most highly suppressive. In contrast, TNFR2(-) Tregs exhibited the phenotype of naive cells and only had minimal suppressive activity. Although not typically considered to be Tregs, CD4(+)CD25(-)TNFR2(+) cells nevertheless possessed moderate suppressive activity. Strikingly, the suppressive activity of TNFR2(+) Tregs was considerably more potent than that of reportedly highly suppressive CD103(+) Tregs. In the Lewis lung carcinoma model, more highly suppressive TNFR2(+) Tregs accumulated intratumorally than in the periphery. Thus, TNFR2 identifies a unique subset of mouse Tregs with an activated/memory phenotype and maximal suppressive activity that may account for tumor-infiltrating lymphocyte-mediated immune evasion by tumors.


Functional Disability Among Middle-Aged and Older Adults in China: The Intersecting Roles of Ethnicity, Social Class, and Urban/Rural Residency.
This study explores how ethnicity, family income, and education level differentiate patterns of functional limitations among urban and rural Chinese (aged 45 ≥ years). Based on the 2018 China Family Panel Studies (CFPS) (n = 16,589), this nationwide study employed binary/multinomial logistic regression analyses, stratified by urban/rural residency, to estimate the likelihood of instrumental activities of daily living (IADLs) disability (0/1-2/≥3 limitations) by social determinants of health (SDoH). The estimated overall prevalence of IADLs disability was 14.3%. The multivariable analyses did not find significant ethnic disparity in IADLs disability in urban China, while in rural China, ethnic minorities were 44% more likely to have IADLs disability than Han Chinese. Among rural residents, Mongolians, Tibetans, and Yi minority more than tripled the odds of having ≥3 limitations than Han Chinese; and the intersections of ethnicity and social class were associated with functional limitations. Long-term care and anti-poverty programs should target minority aging populations in rural China.


Public dental expenditures and dental visits among children in the U.S., 1996-2004.
Congress created the State Children's Health Insurance Program (SCHIP) in 1997 as an expansion of the Medicaid program to provide health insurance to children whose family income is above the Medicaid eligibility standards-generally up to 200% of the federal poverty level (FPL). This article examines changes in the utilization of dental services during a period of increasing public funding of dental services. Public dental expenditure estimates came from the Centers for Medicare & Medicaid Services (CMS), and a breakdown of these expenditures by patient age and income level was based on the Medical Expenditure Panel Survey (MEPS). According to CMS, funding for dental SCHIP and dental SCHIP expansion grew from $0 prior to 1998 to $517 million in 2004. According to the MEPS, between 1996 and 2004 there was an increase in the number and percent of children 2 to 20 years of age who reported a dental visit during the past year. These increases were most notable among children in the 100% to 200% FPL category. Approximately 900,000 more children in this income group visited a dentist in 2003-2004 than in 1996-1997. Children in this income group reported an increase in the amount of mean dental charges paid for by Medicaid and a real increase in mean dental charges per patient from $217 to $310. Recent increases in the public funding of dental services targeted to children in the 100% to 200% FPL category were related to increased utilization of dental services among these children from 1996 to 2004.


Chasing tics in the human brain: development of open, scheduled and closed loop responsive approaches to deep brain stimulation for tourette syndrome.
Tourette syndrome is a childhood-onset disorder characterized by a combination of motor and vocal tics, often associated with psychiatric comorbidities including attention deficit and hyperactivity disorder and obsessive-compulsive disorder. Despite an onset early in life, half of patients may present symptoms in adulthood, with variable degrees of severity. In select cases, the syndrome may lead to significant physical and social impairment, and a worrisome risk for self injury. Evolving research has provided evidence supporting the idea that the pathophysiology of Tourette syndrome is directly related to a disrupted circuit involving the cortex and subcortical structures, including the basal ganglia, nucleus accumbens, and the amygdala. There has also been a notion that a dysfunctional group of neurons in the putamen contributes to an abnormal facilitation of competing motor responses in basal ganglia structures ultimately underpinning the generation of tics. Surgical therapies for Tourette syndrome have been reserved for a small group of patients not responding to behavioral and pharmacological therapies, and these therapies have been directed at modulating the underlying pathophysiology. Lesion therapy as well as deep brain stimulation has been observed to suppress tics in at least some of these cases. In this article, we will review the clinical aspects of Tourette syndrome, as well as the evolution of surgical approaches and we will discuss the evidence and clinical responses to deep brain stimulation in various brain targets. We will also discuss ongoing research and future directions as well as approaches for open, scheduled and closed loop feedback-driven electrical stimulation for the treatment of Tourette syndrome.


In Vitro Evidence of Selective Pro-Apoptotic Action of the Pure Cannabidiol and Cannabidiol-Rich Extract.
Plant cannabinoids, secondary metabolites of species belonging to the Cannabis genus, can mimic the endocannabinoids' action and exert biological effects. Considering the contribution of the endocannabinoid system in cell cycle and apoptotic regulation, there is an interest in exploring the potential anti-cancer activities of natural and synthetic cannabinoids. Cannabidiol (CBD), an abundant plant cannabinoid, reveals a low affinity to cannabinoid receptors and, contrary to various cannabinoids, lacks psychoactive action. Here, we present the in vitro assessment of the pro-apoptototic potential of CBD-rich extracts of Cannabis sativa L. (eCBD) compared to purified CBD (pCBD). As demonstrated, both eCBD and pCBD decreased the viability of breast cancer cell line MDA-MB-231 and human prostate cancer cell line PC-3 in a concentration-dependent fashion. Endoplasmic reticulum stress-related apoptosis and morphological changes were induced only in low-serum conditions. Moreover, the effects of eCDB and pCDB were also assessed in non-malignant cell lines (MCF-10A and PNT2) with no alterations of viability noted, ultimately suggesting a selective action of CBD in tumor cells. The results suggest the possible involvement of reactive oxygen species in the response mechanism to eCBD and pCBD, but no clear pattern was observed. We also demonstrated significant changes in gene expression involved in apoptosis and cell cycle control upon extract treatment. Altogether, our study shows the potential of eCBD and pCBD as novel pro-apoptototic agents that can be considered promising in future preclinical and clinical testing.


Clinical Immunology - a Distinct Area of Immunology.
At academic institutions, clinical immunologists are developing training programs and continuing education programs to meet the needs of physician-immunologists and of organ-based specialists with an interest in immunology. Successful interaction between clinical immunology and organ-based subspecialties is important. Training in both the organ subspecialty and in clinical immunology is necessary for appropriate medical care of most immune-released diseases. Although individual countries differ in their approaches to training, examination and certification, there has been substantial progress toward establishing clinical immunology as a clinical subspecialty or as an area of special qualification.


Interdependence of two NarK domains in a fused nitrate/nitrite transporter.
Nitrate uptake is essential for various bacterial processes and combines with nitrite export to form the usual initial steps of denitrification, a process that reduces nitrate to dinitrogen gas. Although many bacterial species contain NarK-like transporters that are proposed to function as either nitrate/proton symporters or nitrate/nitrite antiporters based on sequence homology, these transporters remain, in general, poorly characterized. Several bacteria appear to contain a transporter that is a fusion of two NarK-like proteins, although the significance of this arrangement remains elusive. We demonstrate that NarK from Paracoccus denitrificans is expressed as a fusion of two NarK-like transporters. NarK1 and NarK2 are separately capable of supporting anaerobic denitrifying growth but with growth defects that are partially mitigated by coexpression of the two domains. NarK1 appears to be a nitrate/proton symporter with high affinity for nitrate and NarK2 a nitrate/nitrite antiporter with lower affinity for nitrate. Each transporter requires two conserved arginine residues for activity. A transporter consisting of inactivated NarK1 fused to active NarK2 has a dramatically increased affinity for nitrate compared with NarK2 alone, implying a functional interaction between the two domains. A potential model for nitrate and nitrite transport in P. denitrificans is proposed.


Characteristics of vestibular corrective saccades in patients with slow visual saccades, vestibular disorders and controls: A descriptive analysis.
Our aim was to determine whether overt catch up saccades (OS) provoked by vestibular stimuli, as observed in the video head impulse test (vHIT), have comparable metrics as visually triggered horizontal saccades (VS), indicating a common saccadic brainstem generator. Three groups of patients were studied: patients with neurological disorders causing slow saccades (group 1, n = 12), patients with peripheral vestibular lesions (group 2, n = 43), and normal controls (group 3, = 24). All patients underwent vHIT and Videooculographic testing. OS velocity, acceleration, amplitude and duration and VS velocity in this group was compared between the groups. There was significant reduction in the velocity of visually guided saccades in group 1, as expected from the patient selection constraints of this study. Group 1 also exhibited saccades which were longer in duration and of reduced acceleration when compared to subjects without saccadic slowing to visual targets (Group 2 and 3). There were significant positive correlations between OS acceleration and amplitude in both normal saccade groups (2 and 3) which was not observed in the slow saccade group (1). The metrics of overt saccades measured by the vHIT in patients with slow saccades and normal controls are similar to visually guided saccades. This supports the hypothesis that overt saccades associated with vestibular stimuli and visually triggered saccades share common circuitry that controls metrics.


Long-term stability of intraocular lenses: literature review, assessment, and testing protocol.
A critical review of the literature confirms the generally excellent, very long-term clinical stability and performance of polymethylmethacrylate (PMMA) in intraocular lenses. In contrast, only short-term, largely nonsystematic data are available on the performance of other, newer materials, such as soft silicones based on polydimethylsiloxane and copolymers of dimethyl- and diphenylsiloxane, hydrogels based on poly(2-hydroxyethylmethacrylate), and various "temporary" and "permanent" hydrophilic coatings. Some conflicting reports have been published on the long-term stability of isotactic polypropylene loop materials. However, the medical consensus seems to be that these are essentially stable to ultraviolet light energy reaching intraocular lenses during the expected service life in excess of 20 years. Uncertainty still surrounds the use of various ultraviolet-absorbing chromophores in the optics and/or haptics of intraocular lenses. Published reports indicate varying transmittance and effectiveness of ultraviolet-absorbing intraocular lenses. Furthermore, there is concern about the fate of the ultraviolet-absorbing chromophores during clinical conditions, especially with regard to degradation and leaching. Although a number of papers has been published on the effect of ultraviolet light energy on intraocular lenses, the experimental approaches differed substantively, so that intercomparative deductions must be made guardedly. A few papers have been published on the long-term biostability (hydrolytic, oxidative, and enzymatic) of intraocular lens materials. However, much of what has appeared in the literature is often illustrative of simplistic assumptions that largely ignore the environment of the eye. Clearly, the eventual success of newer materials must be based on performance characteristics that exceed those of the time-tested polymethylmethacrylate and the refined manufacturing technology designed to transform this polymer into intraocular lenses. The unquestioned clinical success of intraocular lenses rests on long historical data with PMMA that are unavailable with proposed newer materials. Thus, the entry of such new materials into the commercial market, meriting the acceptance of clinicians (and patients), must follow rather than precede thorough in vitro accelerated testing procedures under conditions that permit intercomparative conclusions and recommendations.


[Mesenchymal stem cells and bone regeneration].
Mesenchymal stem cells (MSC) are a cell population present not only in the bone marrow, but also in a number of adult and fetal tissues. Their multilineage differentiation in vitro emphasizes their potential usefulness in the field of the regenerative medicine. New techniques of molecular biology and genetic manipulation of MSC are under investigation for cell therapy of several bone diseases.


A records retention primer.
Today's healthcare financial managers are faced with the challenge of controlling costs and providing quality care while maintaining the necessary records to comply with government requirements and observe sound business practices.


Effectiveness of physical activity promotion based in primary care: systematic review and meta-analysis of randomised controlled trials.
To determine whether trials of physical activity promotion based in primary care show sustained effects on physical activity or fitness in sedentary adults, and whether exercise referral interventions are more effective than other interventions. Systematic review and meta-analysis of randomised controlled trials. Medline, CINAHL, PsycINFO, EMBASE, SPORTDiscus, Centre for Reviews and Dissemination, the Cochrane Library, and article reference lists. Review of randomised controlled trials of physical activity promotion in sedentary adults recruited in primary care, with minimum follow-up of 12 months, reporting physical activity or fitness (or both) as outcomes, and using intention to treat analyses. Two reviewers independently assessed studies for inclusion, appraised risk of bias, and extracted data. Pooled effect sizes were calculated using a random effects model. We included 15 trials (n=8745). Most interventions took place in primary care, included health professionals in delivery, and involved advice or counselling given face to face or by phone (or both) on multiple occasions. Only three trials investigated exercise referral. In 13 trials presenting self reported physical activity, we saw small to medium positive intervention effects at 12 months (odds ratio 1.42, 95% confidence interval 1.17 to 1.73; standardised mean difference 0.25, 0.11 to 0.38). The number needed to treat with an intervention for one additional sedentary adult to meet internationally recommended levels of activity at 12 months was 12 (7 to 33). In four trials reporting cardiorespiratory fitness, a medium positive effect at 12 months was non-significant (standardised mean difference 0.51, -0.18 to 1.20). Three trials of exercise referral found small non-significant effects on self reported physical activity at 12 months (odds ratio 1.38; 0.98 to 1.95; standardised mean difference 0.20, -0.21 to 0.61). Promotion of physical activity to sedentary adults recruited in primary care significantly increases physical activity levels at 12 months, as measured by self report. We found insufficient evidence to recommend exercise referral schemes over advice or counselling interventions. Primary care commissioners should consider these findings while awaiting further trial evaluation of exercise referral schemes and other primary care interventions, with longer follow-up and use of objective measures of outcome.


Psychosocial needs of boys in secure care for serious or persistent offending.
The mental health of child offenders who are detained in secure settings is a matter of great public and professional concern but there has been little systematic longitudinal research on the outcomes of these problems once the young person has returned to the community. The aims of the present study were to describe the psychosocial outcomes of boys in secure care and to establish if these outcomes were correlated with criminal outcomes. Prospective cohort study of 97 boys whose average age was 14 years when they were admitted to secure units in the North West of England. The boys were followed up on average 2 years later, when outcome data were obtained on 81/97 (83%) cases. The main outcome measure was a standardised assessment of mental health, social and educational needs obtained by interview with the young person and corroborated in most cases by information from informants. All data were then reviewed by experienced clinicians who made best-estimate ratings of need 'blind' to the findings from the first phase of the study. The average number of needs requiring an intervention at follow-up (mean=3.4, sd=3.0) was much lower than before admission to secure care (mean=8.2, sd=2.5) (mean difference 4.9 needs, 95% CI 4.0 to 5.7). Educational and occupational needs were particularly well dealt with. However, many mental health problems persisted or worsened. For example, 31% had a need for treatment of substance abuse, a significant increase compared with when they were in secure care (percentage difference 21%, 95% CL 9.0% to 32.7%). No mental disorder predicted subsequent offending. Boys who have been in secure care continue to have a high rate of mental health problems. The mental health needs of this group are not, however, static but change over time and with changing circumstances. Services need to be designed to meet these changing needs.


[Long-term results after implantation of autologous cryopreserved parathyroid tissue].
Autologous cryopreserved parathyroid tissue was implanted into 25 patients (12 men and 12 women, median age 45 [24-75] years, and an 18-month-old child) who after a parathyroidectomy for primary or secondary hyperparathyroidism, had developed permanent postoperative hypoparathyroidism. In 12 of the patients it had developed after a second operation for persisting or recurrent hyperparathyroidism. In ten patients it had occurred after total parathyroidectomy and autologous transplantation of fresh parathyroid tissue, in two patients after subtotal parathyroidectomy and in one patient after excision of a solitary parathyroid adenoma following goitre resection. In 22 patients the state of the tissue to be implanted was examined histologically before implantation after defrosting and any necrosis made up by replacement with more than 20 tissue particles. Re-examination took place a median of 40 [3-120] months postoperatively. The high doses of calcium and vitamin D preparations required preoperatively were reduced stepwise in all patients, completely discontinued in 16. At the time of follow-up nine patients were still receiving low doses of calcium and/or vitamin D. Symptoms of hypocalcaemia disappeared in all patients. Thus implantation of autologous cryopreserved parathyroid tissue is a reliable method for the treatment of permanent postoperative hypoparathyroidism.


Catalytic and functional roles of conserved amino acids in the SET domain of the S. cerevisiae lysine methyltransferase Set1.
In S. cerevisiae, the lysine methyltransferase Set1 is a member of the multiprotein complex COMPASS. Set1 catalyzes mono-, di- and trimethylation of the fourth residue, lysine 4, of histone H3 using methyl groups from S-adenosylmethionine, and requires a subset of COMPASS proteins for this activity. The methylation activity of COMPASS regulates gene expression and chromosome segregation in vivo. To improve understanding of the catalytic mechanism of Set1, single amino acid substitutions were made within the SET domain. These Set1 mutants were evaluated in vivo by determining the levels of K4-methylated H3, assaying the strength of gene silencing at the rDNA and using a genetic assessment of kinetochore function as a proxy for defects in Dam1 methylation. The findings indicate that no single conserved active site base is required for H3K4 methylation by Set1. Instead, our data suggest that a number of aromatic residues in the SET domain contribute to the formation of an active site that facilitates substrate binding and dictates product specificity. Further, the results suggest that the attributes of Set1 required for trimethylation of histone H3 are those required for Pol II gene silencing at the rDNA and kinetochore function.


Genetic deletion of sphingosine kinase 1 suppresses mouse breast tumor development in an HER2 transgenic model.
Aberrant sphingolipid metabolism has been reported to promote breast cancer progression. Sphingosine kinase 1 (SphK1) is a key metabolic enzyme for the formation of pro-survival S1P from pro-apoptotic ceramide. The role of SphK1 in breast cancer has been well studied in estrogen receptor (ER)-positive breast cancer; however, its role in human epidermal growth factor 2 (HER2)-positive breast cancer remains unclear. Here, we show that genetic deletion of SphK1 significantly reduced mammary tumor development with reduced tumor incidence and multiplicity in the MMTV-neu transgenic mouse model. Gene expression analysis revealed significant reduction of claudin-2 (CLDN2) expression in tumors from SphK1 deficient mice, suggesting that CLDN2 may mediate SphK1's function. It is remarkable that SphK1 deficiency in HER2-positive breast cancer model inhibited tumor formation by the different mechanism from ER-positive breast cancer. In vitro experiments demonstrated that overexpression of SphK1 in ER-/PR-/HER2+ human breast cancer cells enhanced cell proliferation, colony formation, migration and invasion. Furthermore, immunostaining of SphK1 and CLDN2 in HER2-positive human breast tumors revealed a correlation in high-grade disease. Taken together, these findings suggest that SphK1 may play a pivotal role in HER2-positive breast carcinogenesis. Targeting SphK1 may represent a novel approach for HER2-positive breast cancer chemoprevention and/or treatment.


Lesions of the nasal radix in pediatric patients: diagnosis and management.
Lesions involving the nasal radix are not extremely uncommon in the pediatric population. Such lesions may represent inflammatory or infectious processes, neoplasia, traumatic sequelae, or developmental anomalies, but faulty embryogenesis is considered the most common cause. During my surgical experience, I have encountered nasal dermoids, nasal gliomas, and nasal encephaloceles resulting in lesions at the root of the nose. Each of these has unique features that will affect therapy.


[Antiviral activity of Ingavirin in experimental lethal influenza due to influenza virus B in albino mice].
The protective activity of Ingavirin against experimental infection caused by influenza B virus was studied on albino mice vs. Arbidol. Oral use of Ingavirin was shown to decrease the infectious titers of the virus in the animal lung tissue, to normalize the body weight dynamics, to lower the mortality and to increase the average lifespan vs. the placebo-treated animals. The activity of Ingavirin was higher than that of the reference drug. The results allowed to consider Ingavirin as a prospective agent for the treatment of influenza infection in humans.


Clinician barriers to initiating sexual health conversations with breast cancer survivors: The influence of assumptions and situational constraints.
Sexual health (SH) is an important dimension of physical, emotional, and social functioning after breast cancer (BC). Research suggests that survivors' SH concerns are not being adequately addressed in oncology or primary care settings. It is important to understand why these conversations are not taking place and what can be done to enhance care for women in this context. This research aims to identify when clinicians initiate SH conversations with survivors and to uncover factors that influence these decisions. Thirty-six clinicians from family medicine, internal medicine, oncology, and gynecology participated in semistructured interviews. Analysis uncovered themes that influence clinicians' decisions about initiating SH conversations with survivors. Attention was given to capturing the personal, professional, and system-level issues that inform clinicians' communication choices. Clinicians reported their decisions are based on (a) beliefs about patients, (b) inability to address survivors' concerns, (c) time constraints that affect the delivery of care, and (d) views of professional function in survivor health care. Clinician decisions are based on sometimes-erroneous assumptions and situational constraints. This suggests the need for medical education and support regarding SH care. Several practice points are outlined to facilitate clinicians' efforts to improve SH care for female BC survivors. (PsycINFO Database Record


The combined effect of signal decorrelation and random noise on the variance of time delay estimation.
Tissue motion and elasticity imaging techniques commonly use time delay estimation (TDE) for the assessment of tissue displacement. The performance of these techniques is limited because the signals are corrupted by various factors including electronic noise, quantization, and speckle decorrelation. Speckle decorrelation is caused by changes in the coherent interference among scatterers when the tissue moves relative to the ultrasound beam. In time delay estimation, the effect of noise is usually addressed through the signal-to-noise ratio (SNR) term. Decorrelation, often a significant source of error in medical ultrasound, is commonly described in terms of the correlation coefficient. A relationship between the correlation coefficient and the SNR was previously derived in the literature, for identical signals corrupted by uncorrelated random noise. In this paper, we derive the relationship between the peak of the correlation coefficient function and the SNR for two jointly stationary signals when a delay is present between the signals. Recently, an expression for the Cramer-Rao lower bound (CRLB) has been derived in the literature for partially decorrelated signals in terms of the SNR and the correlation coefficient. Since the applicability of the CRLB is determined not only by the SNR, but also by the correlation coefficient, it is important to unify the expression for the CRLB for partially correlated signals. In this paper, we derive an expression for the CRLB in term of an equivalent SNR converted from the correlation coefficient using an SNR-p relationship, and show this expression to be equivalent to the expression for CRLB. We also corroborate the validity of the SNR-p expression with a simulation. Using this formulation, correlation measurements can be converted to SNR to obtain a composite SNR. The use of this composite SNR in lieu of those in the CRLB expression in the literature allows the extension of the literature results to the solution of the common TDE problems that involve signal decorrelation.


Contributions of Parietal Cortex to the Working Memory of an Obstacle Acquired Visually or Tactilely in the Locomoting Cat.
A working memory of obstacles is essential for navigating complex, cluttered terrain. In quadrupeds, it has been proposed that parietal cortical areas related to movement planning and working memory may be important for guiding the hindlegs over an obstacle previously cleared by the forelegs. To test this hypothesis, parietal areas 5 and 7 were reversibly deactivated in walking cats. The working memory of an obstacle was assessed in both a visually dependent and tactilely dependent paradigm. Reversible bilateral deactivation of area 5, but not area 7, altered hindleg stepping in a manner indicating that the animals did not recall the obstacle over which their forelegs had stepped. Similar deficits were observed when area 5 deactivation was restricted to the delay during which obstacle memory must be maintained. Furthermore, partial memory recovery observed when area 5 function was deactivated and restored within this maintenance period suggests that the deactivation may suppress, but not eliminate, the working memory of an obstacle. As area 5 deactivations incurred similar memory deficits in both visual and tactile obstacle working memory paradigms, parietal area 5 is critical for maintaining the working memory of an obstacle acquired via vision or touch that is used to modify stepping for avoidance.


[Insurgent physicians and surgeons].
The long way toward the Mexican Independence developed in various stages, each one characterized by the temperament of the leaders, the theater of war actions and the social instances. At the beginning of the movement, of popular and radical types, we find few physicians perhaps due to the small number of them in the cities and to their absence in the villages. The middle period shows a larger number of national and foreign physicians. They are present in a more important number during the last stage, of bourgeois and reformist characteristics. The comportment of these worthy members of the medical class, during the different stages of the national independence movement, is a clear example of the patriotism and honesty of the Mexican physicians.


Correlation of pharmacokinetic indices with therapeutic outcome in patients receiving aminoglycosides.
The influence of five pharmacokinetic indices on therapeutic response was retrospectively studied in 45 adult patients treated with aminoglycosides for bacterial infections. Subjects were treated for a minimum of five days, had culture and sensitivity reports, and had at least one set of steady-state peak and trough serum aminoglycoside concentrations. Serum drug concentrations were determined by enzyme-multiplied immunoassay or by fluorescence polarization assay. Minimum inhibitory concentrations (MICs) for the drugs were determined by microdilution assays. Cure was determined by negative cultures or absence of clinical evidence of infection. Values for five pharmacokinetic indices were determined for each patient: ratio of steady-state peak serum concentration to MIC (Cssmax/MIC); time that the serum concentration remained above the MIC during a 72-hour period (tsupra-MIC(72)); the intensity index for a 72-hour period (II(72)), which is related but not identical to the area under the curve (AUC), reflecting the contributions of Cssmax/MIC and tsupra-MIC(72); time that the serum concentration was greater than four times the MIC during a 72-hour period (tsupra-(4 X MIC)(72)), and the intensity index related but not identical to AUC greater than four times the MIC (II4 X MIC(72)), which reflects the contribution of Cssmax/(4 X MIC) and tsupra-(4 X MIC)(72). Statistical analysis revealed significant correlations between each of the five indices and the patients' therapeutic responses. The following index values were associated with cures: Cssmax/MIC greater than 4 (and ideally greater than 8); tsupra-MIC(72) of at least 40 hours; tsupra-(4 X MIC)(72) of at least 10 hours; (4) II(72) greater than 400; and II4 X MIC(72) greater than 50. All five pharmacokinetic indices were good predictors of patient outcome. The ratio of maximum steady-state serum aminoglycoside concentration to minimum inhibitory concentration is the index most easily monitored and interpreted.


Rapid Implementation of Video Visits in Neurology During COVID-19: Mixed Methods Evaluation.
Telemedicine has been used for decades. Despite its many advantages, its uptake and rigorous evaluation of feasibility across neurology's ambulatory subspecialties has been sparse. However, the COVID-19 pandemic prompted health care systems worldwide to reconsider traditional health care delivery. To safeguard health care workers and patients, many health care systems quickly transitioned to telemedicine, including across neurology subspecialties, providing a new opportunity to evaluate this modality of care. To evaluate the accelerated implementation of video visits in ambulatory neurology during the COVID-19 pandemic, we used mixed methods to assess adoption, acceptability, appropriateness, and perceptions of potential sustainability. Video visits were launched rapidly in ambulatory neurology clinics of a large academic medical center. To assess adoption, we analyzed clinician-level scheduling data collected between March 22 and May 16, 2020. We assessed acceptability, appropriateness, and sustainability via a clinician survey (n=48) and semistructured interviews with providers (n=30) completed between March and May 2020. Video visits were adopted rapidly; overall, 65 (98%) clinicians integrated video visits into their workflow within the first 6 implementation weeks and 92% of all visits were conducted via video. Video visits were largely considered acceptable by clinicians, although various technological issues impacted their satisfaction. Video visits were reported to be more convenient for patients, families, and caregivers than in-person visits; however, access to technology, the patient's technological capacity, and language difficulties were considered barriers. Many clinicians expressed optimism about future utilization of video visits in neurology. They believed that video visits promote continuity of care and can be incorporated into their practice long-term, although several insisted that they can never replace the in-person examination. Video visits are an important addition to clinical care in ambulatory neurology and are anticipated to remain a permanent supplement to in-person visits, promoting patient care continuity, and flexibility for patients and clinicians alike.


Change in and long-term investigation of neuro-otologic disorders in disaster-stricken Fukushima prefecture: retrospective cohort study before and after the Great East Japan Earthquake.
On March 11, 2011, Japan's northeast Pacific coast was hit by a gigantic earthquake and subsequent tsunami. Soma City in Fukushima Prefecture is situated approximately 44 km north of Fukushima Daiichi Nuclear Power Plant. Soma General Hospital is the only hospital in Soma City that provides full-time otolaryngological medical care. We investigated the changes in new patients from one year before to three years after the disaster. We investigated 18,167 new patients treated at our department during the four years from April 1, 2010 to March 31, 2014. Of the new patients, we categorized the diagnoses into Meniere's disease, acute low-tone sensorineural hearing loss, vertigo, sudden deafness, tinnitus, and facial palsy as neuro-otologic symptoms. We also investigated the changes in the numbers of patients whom we examined at that time concerning other otolaryngological disorders, including epistaxis, infectious diseases of the laryngopharynx, and allergic rhinitis. The total number of new patients did not change remarkably on a year-to-year basis. Conversely, cases of vertigo, Meniere's disease, and acute low-tone sensorineural hearing loss increased in number immediately after the disaster, reaching a plateau in the second year and slightly decreasing in the third year. Specifically, 4.8% of patients suffering from these neuro-otologic diseases had complications from depression and other mental diseases. With regard to new patients in our department, there was no apparent increase in the number of patients suffering from diseases other than neuro-otologic diseases, including epistaxis, and allergic rhinitis. Patients suffering from vertigo and/or dizziness increased during the first few years after the disaster. These results are attributed to the continuing stress and tension of the inhabitants. This investigation of those living in the disaster area highlights the need for long-term support.


Biographical disruption, adjustment and reconstruction of everyday occupations and work participation after mild traumatic brain injury. A focus group study.
To explore traumatic brain injury (TBI) as a biographical disruption and to study the reconstruction of everyday occupations and work participation among individuals with mild TBI. Seven focus groups were conducted with 12 women and 8 men (22-60 years) who had sustained mild TBI and participated in a return-to-work program. Interviews were analyzed using qualitative content analysis. Four interrelated themes emerged: disruption of occupational capacity and balance; changes in self-perceptions; experience of time; and occupational adjustment and reconstruction. The meaning of the impairments lies in their impact on the individual's everyday occupations. The abandonment of meaningful daily occupations and the feeling of not recognizing oneself were experienced as threats to the sense of self. Successful integration of the past, present and future was paramount to continuing life activities. The unpredictability of the future seemed to permeate the entire process of adjustment and reconstruction of daily life. Our findings show that the concept of time is important in understanding and supporting the reconstruction of daily life after TBI. The fundamental work of rehabilitation is to ameliorate the disruptions caused by the injury, restoring a sense of personal narrative and supporting the ability to move forward with life. Implications for Rehabilitation Individuals with a protracted recovery after a mild traumatic brain injury must reconstruct a new way of being and acting in the world to achieve biographical continuity. The perceived anxiety regarding changes in self and occupational identity, as well as loss of control over the future, can be attenuated through informational sessions during the hospital stay and at follow-up visits. The significant personal costs of returning to full-time employment too early indicate the need for early and ongoing vocational support in achieving a successful return to work.


[Guide for the prevention and treatment of coronavirus disease 2019].
In December 2019, a novel coronavirus was identified in Wuhan City, Hubei Province, China and later the disease was named coronavirus disease 2019 (COVID-19) . On March 11, 2020, the World Health Organization (WHO) officially announced that COVID-19 had reached global pandemic status. This article summarized the understanding of the etiology, pathogenesis, epidemiology, clinical characteristics, diagnosis, treatment, rehabilitation, and prevention and control measures of COVID-19 based on the available data and anti-epidemic experience in China.