[The clinical characteristics of pulmonary benign metastasizing leiomyoma].
Objective: Pulmonary benign metastasizing leiomyoma (PBML) is a rare entity that leiomyoma of uterus metastasized to the lung. The clinical characteristics of this rare disease were analyzed in this article. Methods: The detailed clinical records of 7 patients diagnosed as PBML at Peking Union Medical College Hospital between January 2001 and June 2015 were reviewed. Results: All patients were women with median age of 44 years (range 28-62). Symptoms included dyspnea (2/7), chest pain (1/7), cyanosis (1/7), cough (1/7) and bloody sputum (1/7), while 4/7 cases were asymptomatic. Six patients had the past-history of leiomyoma of uterus 20 months to 14 years ago among whom 5 patients received hysterectomy. Chest CT showed bilateral, random-distributed multiple round solid nodules, or diffuse-distributed miliary nodules, or single solid nodule, even some small cavities. Extra-pulmonary metastasis was found in left superclavicular lymph node (1 case) and right heart (1 case). Histological tissues were obtained by video-assisted thoracic surgery lung biopsy (4/7), mass resection on tricuspid valve (1/7), transbronchil lung biopsy (1/7), and CT-guided percutaneous lung biopsy (1/7). Pathology showed an interlacing pattern by spindle cells having elongated nuclei without cellular atypia. Ki-67 index was less than 1%. Molecules such as smooth muscle antibody, estrogen receptor (ER) and progestrone receptor (PR) were positive in immunohistochemistry staining. Neither letrozole nor zoladex was effective. Two patients responded to bilateral adnexectomy, presenting as shrunk nodules. No relapsed disease was seen in one patient with single nodule after resection. There was only one patient with disease-related mortality, whose chest CT showed milliary nodules. Conclusion: Although CT findings of PBML are similar to malignancies, the clinical outcome is good. Despite the positive expression of ER and PR, the effectiveness of hormone related treatment is limited. And periodical follow up is suggested even to those uneventful patients.


Draft genome sequence of the human pathogen Streptomyces somaliensis, a significant cause of actinomycetoma.
We report the draft genome sequence of the human pathogen Streptomyces somaliensis (DSM 40738), a pathogen within a genus of largely saprophytic organisms. S. somaliensis causes severe and debilitating deep tissue and bone infections. The genome sequence is deposited in DDBJ/EMBL/GenBank with the accession number AJJM01000000.


Supercritical processed starch nanosponge as a carrier for enhancement of dissolution and pharmacological efficacy of fenofibrate.
In current study, supercritical processed starch nanosponge (SSNS) used as a carrier for poorly water soluble drug (fenofibrate) to enhance its in-vitro and in-vivo performance. SSNS was prepared by using sol- gel method and effective supercritical drying technique. Fenofibrate was loaded into the SSNS by using solvent immersion method with selected and optimized organic solvent. BET surface area of SSNS was evaluated by nitrogen adsorption/desorption analysis. SSNS and drug loaded SSNS were characterized by DSC, XRPD, FTIR, SEM, Contact angle study and evaluated for in-vitro, in-vivo studies. The results revealed that the formed SSNS material has high surface area (180m2/gm) with pore size (40 nm to 200nm). The DSC and XRPD study revealed the amorphization of drug within a SSNS. SEM study showed the continuous porous structure with differ nanosized pores of SSNS. Contact angle study showed improvement in aqueous wetting property of drug within a SSNS. In-vitro drug release study showed remarkable dissolution enhancement of SSNS formulation as compared to plain drug. In vivo pharmacodynamic study (hyperlipidaemia model) showed SNSS based formulation significantly improved the bioavailability of drug. Thus SSNS carrier system has good potential to be explored as a delivery system for poorly water soluble drugs.


Risk of relapse to non-opioid addictive substances among opioid dependent patients treated with an opioid receptor antagonist or a partial agonist: A randomized clinical trial.
First study to assess any compensatory increase in use of non-opioid illicit substances and alcohol in opioid dependent patients randomized to treatment with extended-release naltrexone (XR-NTX) or buprenorphine-naloxone (BP-NLX) and in longer term treatment with extended-release naltrexone. A multicenter, outpatient, open-label randomized clinical trial where patients received intramuscular extended-release naltrexone hydrochloride, 380 mg/month, or daily sublingual buprenorphine-naloxone 8-24/2-6 mg for 12 weeks, and an option to continue with extended-release naltrexone for an additional 36 week follow-up. The study was conducted at five urban addiction clinics and detoxification units in Norway between November 2012, and July 2016. Among the 143 patients, 106 men and 37 women, there were no significant differences between those randomized to XR-NTX or BP-NLX in the risk of first relapse to alcohol (HR 1.31; 0.68-2.53), amphetamines (HR 0.88; 0.43-1.80), benzodiazepines (HR 1.24; 0.74-2.09) or cannabis (HR 1.55; 0.83-2.89). Also in the 36-week (12-48 weeks) follow-up period we found no significant differences between patients continuing with XR-NTX compared to those switching to XR-NTX after the randomized period in risk of first relapse to any non-opioid substance. In both study periods, the mean time in the study were longer among those relapsing to non-opioid addictive substances than those who did not. There was no significant association between first relapse to illicit opioids and first relapse to non-opioid addictive substances. There was no increase in the risk of relapse to non-opioid addictive substances neither in short term nor longer-term treatment with extended-release naltrexone. Trial registrationclinicaltrials.gov Identifier: NCT01717963.


Technical advances in global DNA methylation analysis in human cancers.
Prototypical abnormalities of genome-wide DNA methylation constitute the most widely investigated epigenetic mechanism in human cancers. Errors in the cellular machinery to faithfully replicate the global 5-methylcytosine (5mC) patterns, commonly observed during tumorigenesis, give rise to misregulated biological pathways beneficial to the rapidly propagating tumor mass but deleterious to the healthy tissues of the affected individual. A growing body of evidence suggests that the global DNA methylation levels could serve as utilitarian biomarkers in certain cancer types. Important breakthroughs in the recent years have uncovered further oxidized derivatives of 5mC - 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), thereby expanding our understanding of the DNA methylation dynamics. While the biological roles of these epigenetic derivatives are being extensively characterized, this review presents a perspective on the opportunity of innovation in the global methylation analysis platforms. While multiple methods for global analysis of 5mC in clinical samples exist and have been reviewed elsewhere, two of the established methods - Liquid Chromatography coupled with mass spectrometry (LC-MS/MS) and Immunoquantification have successfully evolved to include the quantitation of 5hmC, 5fC and 5caC. Although the analytical performance of LC-MS/MS is superior, the simplicity afforded by the experimental procedure of immunoquantitation ensures it's near ubiquity in clinical applications. Recent developments in spectroscopy, nanotechnology and sequencing also provide immense promise for future evaluations and are discussed briefly. Finally, we provide a perspective on the current scenario of global DNA methylation analysis tools and present suggestions to develop the next generation toolset.


Effect of the semen extract of Thuja orientalis on inflammatory responses in transient focal cerebral ischemia rat model and LPS-stimulated BV-2 microglia.
In the central nervous system inflammation is dependent upon the synthesis of various inflammatory mediators by local neurons, astrocytes and especially microglia. In this study, we investigated the anti-inflammatory activities of the semen extract of Thuja orientalis (Thujae Orientalis Semen; TOS) on transient middle cerebral artery occlusion (tMCAO)-induced ischemia in rats and the production of inflammatory mediators such as nitric oxide (NO), prostaglandin E(2) (PGE(2)) and proinflammatory cytokine, interleukin (IL)-1β in lipopolysaccharide (LPS)-stimulated BV-2 mouse microglia. TOS extract significantly decreased the infarction volumes of ischemic brains and also inhibited microglia activation and neuronal death. In addition, TOS extract significantly decreased the production of NO, PGE(2) and IL-1β in LPS-stimulated BV-2 microglia. TOS extract also attenuated the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and IL-1β mRNAs and proteins in activated microglia. Furthermore, TOS extract significantly suppressed the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAPK, and the nuclear translocation of NF-κB p65 in activated microglia. Our results indicate that TOS extract is capable of inhibiting microglia activation in an ischemic brain through the down-regulation of inflammatory responses, suggesting that the TOS extract may have therapeutic potential as an anti-inflammatory drug for ischemic stroke.


Expertise and advocacy in animal-welfare decision making: considerations for a veterinary curriculum in animal welfare.
An animal-welfare curriculum for veterinary students should provide learning opportunities in the application of veterinary expertise to patient management and animal-welfare policy. Real-life and hypothetical cases are presented that can allow students to develop their personal-values statement about animal welfare, explore the interaction of facts and values in deciding on a course of action, and understand the unique obligations and authority they will have as veterinarians.


[Prognostic value of changes of peripheral blood T cell subsets after thermoradiotherapy for nasopharyngeal carcinoma].
To assess the prognostic value of changes of peripheral blood T cell subsets after thermoradiotherapy for nasopharyngeal carcinoma (NPC). Peripheral blood T cell subsets in 20 normal subjects (control group), 30 NPC patients undergoing thermoradiotherapy, and 20 NPC patients undergoing radiotherapy were detected by flow cytometry. The percentages of CD3+CD4+ and CD8+CD28+ cells were decreased and the percentages of CD3+CD8+ and CD8+CD28- cells increased as compared with the measurements in normal persons. One month after thermoradiotherapy, the percentages of CD3+CD4+ and CD8+CD28+ cells further decreased and the percentages of CD3+CD8+ and CD8+CD28- cells further increased, which continued to worsen 3 months after the treatment and appeared to be related to the survival of the patients. T cell subsets of NPC patients are abnormal and their immune functions depressed in NPC patients within a long period after thermoradiotherapy. CD8+CD28+ and CD8+CD28- T cell subsets can be significant for prognostic assessment in these patients after thermoradiotherapy.


Inhibition of NLRP3 Inflammasome Pathway by Butyrate Improves Corneal Wound Healing in Corneal Alkali Burn.
Epithelial cells are involved in the regulation of innate and adaptive immunity in response to different stresses. The purpose of this study was to investigate if alkali-injured corneal epithelia activate innate immunity through the nucleotide-binding oligomerization domain-containing protein (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway. A unilateral alkali burn (AB) was created in the central cornea of C57BL/6 mice. Mice received either no topical treatment or topical treatment with sodium butyrate (NaB), β-hydroxybutyric acid (HBA), dexamethasone (Dex), or vehicle (balanced salt solution, BSS) quater in die (QID) for two or five days (d). We evaluated the expression of inflammasome components including NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1, as well as the downstream cytokine interleukin (IL)-1β. We found elevation of NLRP3 and IL-1β messenger RNA (mRNA) transcripts, as well as levels of inflammasome component proteins in the alkali-injured corneas compared to naïve corneas. Treatment with NLRP3 inhibitors using NaB and HBA preserved corneal clarity and decreased NLRP3, caspase-1, and IL-1β mRNA transcripts, as well as NLRP3 protein expression on post-injury compared to BSS-treated corneas. These findings identified a novel innate immune signaling pathway activated by AB. Blocking the NLRP3 pathway in AB mouse model decreases inflammation, resulting in greater corneal clarity. These results provide a mechanistic basis for optimizing therapeutic intervention in alkali injured eyes.


Noninvasive estimation of cardiac systolic function using continuous-wave Doppler echocardiography in dogs with experimental mitral regurgitation.
To evaluate the feasibility of noninvasive estimation of cardiac systolic function using transthoracic continuous-wave Doppler echocardiography in dogs with mitral regurgitation. Seven mongrel dogs with experimental mitral regurgitation were used. Left ventriculography and measurement of pulmonary capillary wedge pressure were performed under inhalational anaesthesia. A micromanometer-tipped catheter was placed into the left ventricle and transthoracic echocardiography was carried out. The peak rate of left ventricular pressure rise (peak dP/dt) was derived simultaneously by continuous-wave Doppler and manometer measurements. The Doppler-derived dP/dt was compared with the catheter-measured peak dP/dt in the dogs. Classification of the severity of mitral regurgitation in the dogs was as follows: 1+, 2 dogs; 2+, 1 dog; 3+, 2 dogs; 4+, 1 dog; and not examined, 1 dog. We were able to derive dP/dt from the transthoracic continuous-wave Doppler echocardiography in all dogs. Doppler-derived dP/dt had a significant correlation with the catheter-measured peak dP/dt (r = 0.90, P < 0.0001). It was demonstrated that transthoracic continuous-wave Doppler echocardiography is a feasible method of noninvasive estimation of cardiac systolic function in dogs with experimental mitral regurgitation and may have clinical usefulness in canine patients with spontaneous mitral regurgitation.


HCV IRES interacts with the 18S rRNA to activate the 40S ribosome for subsequent steps of translation initiation.
Previous analyses of complexes of 40S ribosomal subunits with the hepatitis C virus (HCV) internal ribosome entry site (IRES) have revealed contacts made by the IRES with ribosomal proteins. Here, using chemical probing, we show that the HCV IRES also contacts the backbone and bases of the CCC triplet in the 18S ribosomal RNA (rRNA) expansion segment 7. These contacts presumably provide interplay between IRES domain II and the AUG codon close to ribosomal protein S5, which causes a rearrangement of 18S rRNA structure in the vicinity of the universally conserved nucleotide G1639. As a result, G1639 becomes exposed and the corresponding site of the 40S subunit implicated in transfer RNA discrimination can select . These data are the first demonstration at nucleotide resolution of direct IRES-rRNA interactions and how they induce conformational transition in the 40S subunit allowing the HCV IRES to function without AUG recognition initiation factors.


The seroepidemiology of human immunodeficiency virus in the United States household population: NHANES III, 1988-1991.
To provide an estimate of the seroprevalence of human immunodeficiency virus (HIV) in a representative sample of the U.S. household population, serum samples from participants in the third National Health and Nutrition Examination Survey (NHANES III) were tested for HIV antibody. The testing was performed anonymously on 5,430 individuals 18-59 years old from phase 1 of NHANES III conducted from 1988 to 1991. Twenty-nine individuals were HIV positive. The total weighted prevalence was 0.39%. The population estimate of infected individuals was 547,000, with a 95% confidence interval of 299,000-1,020,000 infected persons. Black participants were four times more likely to be HIV positive than white/other individuals and three times more likely than Mexican Americans. Men were three times more likely to be infected than women. Higher nonresponse to the survey and to phlebotomy was observed in young white men; therefore these data provide a conservative estimate of HIV infection in the general household population. This estimate does not include individuals who do not live in households and who may be at higher risk of infection, such as persons in penal institutions, the homeless, or certain hospitalized patients.


A multicentric study on the newly developed reconstruction locking plate for midshaft clavicular fracture.
Objectives: To examine the efficacy and clinical and radiological outcomes of the use of a streamlined clavicle plate® (MEIRA, Aichi, Japan) for midshaft clavicular fractures. Methods: This was a retrospective cohort study of 155 patients with displaced midshaft clavicular fractures treated using a streamlined clavicle plate between 2015 and 2019 in 18 hospitals across Japan. A questionnaire regarding bone union and postoperative complications was used, and 136 cases were followed up for one year or until bone union. Plate fitting was evaluated retrospectively using surgical records, radiographic findings, and surgeon's opinion. Results: During surgery, plate bending was needed in 19 cases (12.3%), poor fitting was observed in 8 cases (5.2%), and bone union was achieved in 133 cases (97.8%). Total implantation failure, including plate breakage and screw loosening, occurred in 10 cases (6.5%) from the intraoperative to postoperative period. Subjective complications were observed in 26 cases (16.8%): incongruity around the surgical scar or in the anterior chest in 23, and contracture of the shoulder in three. Plate removal was performed in 66 cases (48.5%) per patient's request. Conclusion: The use of a streamlined clavicle plate is effective for midshaft fractures of the clavicle, and the success rates of bone union and implantation using this approach are comparable to those of other existing plates.


[Obesity or overweight and metabolic syndrome in Mexico City teenagers].
aim: To know the metabolic syndrome and its components prevalence in Mexico City adolescents sample. A cross-sectional survey was conducted in 772 men and 1078 women, 12 to 16 years old, from 8 randomly selected public junior high schools in Mexico City. Anthropometric variables, lipids, lipoproteins, Apo AI and B, glucose and insulin were determined. Prevalence of metabolic syndrome was 12.5%, 11.15% in men and 13.5% en women (p ns). The most frequently metabolic syndrome component found in México City adolescents was low HDL-C levels (38%), followed by hypertriglyceridemia (25.5%), hypertension (19.2%), central obesity (11.8%) and elevated fasting glucose (1.7). Except by the hypertriglyceridemia, higher in woman than in men, 28.2% vs. 21.6%, p < 0.001, the prevalence of metabolic syndrome components was similar between males and females. The high prevalence of biochemical and physiological factors of metabolic syndrome, associated with overweight and obesity in Mexico City adolescents, increases the risk of premature development of coronary atherosclerosis and diabetes mellitus in this population.


On-demand multiplexed vortex beams for terahertz polarization detection based on metasurfaces.
The manipulation of polarization states is crucial for tailoring light-matter interactions and has great applications in fundamental science. Nevertheless, conventional polarization measurement approaches are extremely challenging to determine the polarization state of incident terahertz (THz) beams. The combination of metasurfaces and inhomogeneous vector vortex beams (VVBs) provides a new solution for integrated polarization-related functional devices. Herein, a general design strategy for spin-multiplexing all-silicon metasurfaces is presented and demonstrated in THz polarization detection. The employment of basic building blocks with a high aspect ratio (AR) imparts a greater degree of freedom for generating vector beams, and those basic blocks are subsequently utilized to explore the visualized polarization state. With the assistance of a THz near-field scanning system, we evaluate the capability of reconstructing the incident polarization state from the longitudinal polarization component multiplexed by vortex beams with tight focusing characteristics. Not only that, we also utilize the polarization with dynamically varying behavior as the illumination method to elucidate the evolution trend of the polarization state under a single snapshot and establish a visualized parametric model. This work paves the way to realize ultra-compact THz polarization detection-related devices for future applications in remote sensing, high-resolution imaging, and communications.


Biologic and molecular characterization of two newly isolated ras-containing murine leukemia viruses.
A murine sarcoma virus (MSV) was recovered from an (NFS X NS.C58v-1) F1 mouse which developed splenic sarcoma and erythroleukemia 6 months after inoculation with a mink cell focus-inducing murine leukemia virus (MuLV) isolated from an NFS mouse infected with a wild mouse ecotropic MuLV. The MSV, designated NS.C58 MSV-1, induced foci of transformation in mouse and rat fibroblasts, and inoculation of mice of various strains 2 weeks of age or younger resulted in erythroleukemia and sarcomatous lesions in spleen, lymph node, and brain. The MSV provirus was molecularly cloned from a genomic library prepared from transformed non-producer rat cells. The 8.8-kilobase proviral DNA contained a 1.0-kilobase p21 ras coding segment which replaced most of the gp70-encoding portion of an MuLV, most likely the endogenous C58v-1 ecotropic virus. The ras oncogene is closely related to v-Ha-ras by hybridization, expression of p21 protein, and nucleotide sequence. It is nearly identical in sequence to v-bas, the only previously described transduced, activated mouse c-ras. At position 12 in the p21 coding region, arginine is substituted for the naturally occurring glycine present in c-ras. A second MSV isolate is described which is similar to NS.C58 MSV-1 except for a 100- to 200-base-pair deletion in the noncoding region of the ras-containing insert.


Bronchogenic carcinoma a review and study.
The preceding review of bronchogenic carcinoma and our own experience with lung cancer patients, indicate that long-term survival of these patients has only minimally improved. Advanced lung cancer does not significantly respond to the current treatment armamentarium, but present research and clinical trials of such new treatments as immunotherapy and interferon therapy may give hope for the future. At present our biggest weapon against lung cancer is still the elimination of cigarette smoking. Until we achieve this unlikely goal or greatly improve our success in treating the disease, we will need to continue our commitment to assist the patient with lung cancer in achieving the highest quality of life.


Correct calculation of nitrogen charge state passing through highly ionized carbon plasmas.
In the present work, we reanalyze the energy loss experimental data from Cayzac et al. [Nat. Commun. 8, 15693 (2017)10.1038/ncomms15693] using our successful ion charge state theoretical model. We predict lower nitrogen charge values, from 3.5+ to 5.0+, than the ones calculated by Cayzac et al., fitting better to their data. For energy loss estimations, we use the same stopping model, so our predictions agree better with the experimental data only due to our charge state model. Different projectile electron loss and capture processes are taken into account to estimate the projectile charge state. The projectile electron loss, or ionization, with plasma ions and free electrons are considered. On the other hand, the projectile electron capture, or recombination, with plasma free or bound electrons are also considered. The projectile ionization with plasma ions is shown as the main factor that modifies the mean charge of the projectile. Here, the new Kaganovich fitting formula for this projectile ionization is used because it seems to be more accurate than Gryzinsky's fitting in the low energy range. Our charge state model fits better with experimental data than any other model in the bibliography. Thus, it should be considered in any charge state and any energy loss estimation to obtain reliable results in future work.


The effect of magnetisation transfer contrast on cerebrospinal fluid on motion artefacts on fluid-attenuated inversion-recovery images.
We assessed possible advantages of the use of fluid-attenuated inversion-recovery (FLAIR) sequences with magnetisation-transfer contrast (MTC) over conventional FLAIR images. We carried out cranial MRI at 1 tesla on 50 patients with both sequences. In nine patients with multiple sclerosis (MS) we performed a quantitative comparison of the two sequences, looking at the contrast-to-noise ratio between lesions and normal white matter and counting the number of lesions shown using each method. A qualitative comparison on all patients consisted of the analysis of the appearance of the normal parenchyma, of any lesions, and of artefacts, with particular reference to cerebrospinal fluid (CSF) motion artefacts. The quantitative analysis showed no meaningful difference between the two sequences. The cerebral parenchyma and lesions appeared substantially the same with both techniques. With FLAIR MTC there was a clear, and consistent reduction in CSF motion artefacts. FLAIR MTC sequences can usefully be used in place of the conventional sequence at 1 tesla.


Protective effect of misoprostol, a synthetic prostaglandin E1 analog, on cerulein-induced acute pancreatitis in rats.
This study was performed to assess the effects of misoprostol, a synthetic prostaglandin E1 analog, on cerulein-induced pancreatitis. Per group of 10 each, male Wistar rats received either cerulein (2.5 micrograms/kg/h subcutaneously), cerulein and misoprostol (500 micrograms/kg intraperitoneally at 0 and 4 h), or saline. Rats were killed 6 h after the first injection. Misoprostol treatment significantly reduced interstitial edema and acinar cell lesions induced by hyperstimulation. Pancreatic amylase and chymotrypsin contents were increased by cerulein and returned towards control levels in the misoprostol-treated group. The lysosomal volume density and the pancreatic beta-D-glucuronidase activity were significantly increased after hyperstimulation. The two parameters were significantly reduced by misoprostol. A protective effect of misoprostol against lesions induced by cerulein hyperstimulation would be a consequence of a lysosomal stabilizating effect.


Defining the target for radiotherapy of head and neck cancer.
The greatest challenge for radiation therapy is to attain the highest probability of cure with the least morbidity. Implementation of conformal radiotherapy techniques offers the possibility to target irregularly shaped volumes while optimally sparing the normal tissues. This implies however an accurate knowledge of the exact tumour extension. In order to perfectly delineate the primary tumour and to optimise the radiation dose administered to normal tissues, it is necessary for patients to undergo imaging studies. Both anatomical and functional imaging studies are currently being evaluated for treatment planning of head and neck cancer.


[Effects of preoperative parenteral nutritional support with chemotherapy on tumor cell kinetics in gastric cancer patients].
The purpose of this study is to elucidate the effect of preoperative parenteral nutritional support (PNS) plus chemotherapy on tumor cell kinetics. 19 advanced gastric cancer (AGC) patients were divided into the following groups: group A (n = 7): in addition to their oral intake, received a PNS for 5 days, which yielded 117 Kj.kg-1.d-1 of non-protein calories and 0.15g.kg-1.d-1 of nitrogen. Group B(n = 6): were infused with 5-Fu at 8-10mg.kg-1.d-1 for 5 days and mitomycin C at 6-8mg.d-1 on the first and fifth day. Group C (n = 6): received a PNS plus 5-Fu with MMC as group A and B did. Specimens of gastric cancer and normal gastric mucosa were taken endoscopically before and after PNS. All specimens were studied by flow cytometry for cell cycle analysis. The results showed that the frequency of cells in S and proliferative phases were significantly increased after PNS (P < 0.01, P < 0.001), but decreased after PNS+chemotherapy (P < 0.05, P < 0.025). No significant change after single chemotherapy was observed. In conclusion, PNS might enhance the effect of chemotherapy in AGC patients, probably, by stimulation of tumor cell kinetics.


Sample handling for mass spectrometric proteomic investigations of human urine.
Because of its non-invasive sample collection method, human urine is an attractive biological material both for discovering biomarkers and for use in future screening trials for different diseases. Before urine can be used for these applications, standardized protocols for sample handling that optimize protein stability are required. In this explorative study, we examine the influence of different urine collection methods, storage temperatures, storage times, and repetitive freeze-thaw procedures on the protein profiles obtained by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Prospectively collected urine samples from 11 women were collected as either morning or midday specimens. The effects of storage temperature, time to freezing, and freeze-thaw cycles were assessed by calculating the number, intensity, and reproducibility of peaks visualized by SELDI-TOF-MS. On the CM10 array, 122 peaks were detected and 28 peaks were found to be significantly different between urine types, storage temperature and time to freezing. On the IMAC-Cu array, 65 peaks were detected and 1 peak was found to be significantly different according to time to freezing. No significant differences were demonstrated for freeze-thaw cycles. Optimal handling and storage conditions are necessary in clinical urine proteomic investigations. Collection of urine with a single and consistently performed protocol is needed to reduce analytical bias. Collecting only one urine type, which is stored for a limited period at 4°C until freezing at -80°C prior to analysis will provide the most stable profiles.


Processing Effect on L-DOPA, In Vitro Protein and Starch Digestibility, Proximate Composition, and Biological Activities of Promising Legume: Mucuna macrocarpa.
Objective: In the present investigation, the effect of different cooking processes on L-DOPA level, phenolics contents, in vitro protein (IVPD) and starch digestibility (IVSD), and proximate composition with in vitro anti-inflammatory and antioxidant potential of Mucuna macrocarpa (MM) has been evaluated. Methods: The L-DOPA and major phenolics acids quantification of processed samples were done by a reverse-phase high-performance liquid chromatography (RP-HPLC) technique. Proximate composition, elemental quantification, and in vitro protein and starch digestibility of the samples were carried out by using spectrophotometric analysis. The anti-inflammatory activities of samples were evaluated by a human red blood cells (HRBCs) membrane stabilization test and bovine serum albumin (BSA) anti-denaturation assay. Antioxidant potential of processed beans was carried out by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and N,N-dimethyl-p-phenylendiamine (DMPD) assays and ferric reducing/antioxidant power (FRAP) assay. Results: The processed MM beans showed a significant reduction of L-DOPA (6.30%), phytic acid (25.78%), tannin (19.79%), and saponin (25.59%) in the boiling, autoclaving, and roasting processes. RP-HPLC quantification of major phenolics acids was also affected by the differential process as compare to the raw seed sample. The processed seeds also showed considerable improvement of in vitro protein (26.93%) and starch (20.30%) digestibility, whereas the anti-inflammatory potential and antioxidant potential of MM beans were decreased in the processed samples, indicating a reduction of antioxidant molecules. Conclusion: The differential process showed considerable changes in the proximate composition, in vitro digestibility, and biological potential. The present study recommends the utilization of MM beans after autoclaving and boiling for maximum nutritional potential with health benefits.


Comparison of percutaneous venous catheters and teflon catheters for intravenous therapy in neonates.
The purpose of this study was to compare the average duration of catheterization of percutaneous venous catheters (PVCs) with Teflon catheters placed in peripheral veins of neonates, and to describe the incidence of mechanical or infectious complications associated with their use. The sample consisted of twelve subjects with a total of 52 catheters--17 PVCs and 35 Teflon catheters. The results of the study indicated both a significant increase in the duration of catheterization (p = .001) and a significant reduction in the incidence of complications (p = .004) when PVCs were used. The mean duration of catheterization for PVCs was 178.6 hours and for Teflon catheters 41.9 hours. Although 80.8 percent of all the neonates studied suffered some complication leading to early catheter removal, such complications were observed most frequently with Teflon catheters (91 versus 59 percent of PVCs). However, the one subject who experienced the complication of catheter-related sepsis did have a PVC in situ for 313.5 hours. For this sample of neonates, the PVC was the most efficacious mode of IV therapy.


Changes in air pollution exposure after residential relocation and body mass index in children and adolescents: A natural experiment study.
Air pollution exposure may affect child weight gain, but observational studies provide inconsistent evidence. Residential relocation can be leveraged as a natural experiment by studying changes in health outcomes after a sudden change in exposure within an individual. We aimed to evaluate whether changes in air pollution exposure due to residential relocation are associated with changes in body mass index (BMI) in children and adolescents in a natural experiment study. This population-based study included children and adolescents, between 2 and 17 years, who moved during 2011-2018 and were registered in the primary healthcare in Catalonia, Spain (N = 46,644). Outdoor air pollutants (nitrogen dioxides (NO2), particulate matter <10 μm (PM10) and <2.5 μm (PM2.5)) were estimated at residential census tract level before and after relocation; tertile cut-offs were used to define changes in exposure. Routinely measured weight and height were used to calculate age-sex-specific BMI z-scores. A minimum of 180 days after moving was considered to observe zBMI changes according to changes in exposure using linear fixed effects regression. The majority of participants (60-67% depending on the pollutant) moved to areas with similar levels of air pollution, 15-49% to less polluted, and 14-31% to more polluted areas. Moving to areas with more air pollution was associated with zBMI increases for all air pollutants (β NO2 = 0.10(95%CI 0.09; 0.12), β PM2.5 0.06(0.04; 0.07), β PM10 0.08(0.06; 0.10)). Moving to similar air pollution areas was associated with decreases in zBMI for all pollutants. No associations were found for those moving to less polluted areas. Associations with moving to more polluted areas were stronger in preschool- and primary school-ages. Associations did not differ by area deprivation strata. This large, natural experiment study suggests that increases in outdoor air pollution may be associated with child weight gain, supporting ongoing efforts to lower air pollution levels.


Intestine Explants in Organ Culture: A Tool to Broaden the Regenerative Studies in Echinoderms.
The cellular events underlying intestine regrowth in the sea cucumber Holothuria glaberrima have been described by our group. Currently, the molecular and signaling mechanisms involved in this process are being explored. One of the limitations to our investigations has been the absence of suitable cell culture methodologies, required to advance the regeneration studies. An in vitro system, where regenerating intestine explants can be studied in organ culture, was established previously by our group. However, a detailed description of the histological properties of the cultured gut explants was lacking. Here, we used immunocytochemical techniques to study the potential effects of the culture conditions on the histological characteristics of explants, comparing them to the features observed during gut regeneration in our model in vivo. Additionally, the explant outgrowths were morphologically described by phase-contrast microscopy and SEM. Remarkably, intestine explants retain most of their original histoarchitecture for up to 10 days, with few changes as culture time increases. The most evident effects of the culture conditions on explants over culture time were the reduction in the proliferative rate, the loss of the polarity in the localization of proliferating cells, and the appearance of a subpopulation of putative spherulocytes. Finally, cells that migrated from the gut explants could form net-like monolayers, firmly attached to the culture substrate. Overall, regenerating explants in organ culture represent a powerful tool to perform short-term studies of processes associated with gut regeneration in H. glaberrima under controlled conditions.


Growth of HIV-exposed uninfected, compared with HIV-unexposed, Zambian children: a longitudinal analysis from infancy to school age.
Early growth of HIV-exposed, uninfected (HEU) children is poorer than that of their HIV-unexposed, uninfected (HUU) counterparts but there is little longitudinal or longer term information about the growth effects of early HIV exposure. We performed a longitudinal analysis to compare growth of HEU and HUU infants and children using data from two cohort studies in Lusaka, Zambia. Initially 207 HUU and 200 HEU infants from the Breastfeeding and Postpartum Health (BFPH) study and 580 HUU and 165 HEU from the Chilenje Infant Growth, Nutrition and Infection Study (CIGNIS) had anthropometric measurements taken during infancy and again when school-aged, at which time 66 BFPH children and 326 CIGNIS children were available. We analysed the data from the two cohorts separately using linear mixed models. Linear regression models were used as a secondary analysis at the later time points, adjusting for breastfeeding duration. We explored when the main group differences in growth emerged in order to estimate the largest 'effect periods'. After adjusting for socioeconomic status and maternal education, HEU children had lower weight-for-age, length-for-age and BMI-for-age Z-scores during early growth and these differences still existed when children were school-aged. Exposure group differences changed most between 1 and 6 weeks and between 18 months and ~7.5 years. HEU children have poorer early growth than HUU children which persists into later growth. Interventions to improve growth of HEU children need to target pregnant women and infants.


Separation and culture of ovine endometrial epithelial and stromal cells: evidence of morphological and functional polarity.
Epithelial and stromal cells from endometria of ovariectomized estradiol-treated Corriedale ewes were separated and purified after collagenase digestion. The separation method utilized differences in the speed and ease of detachment of cultured epithelial and stromal cells attached to plastic in response to brief trypsin exposure. Cells were characterized according to morphological, growth, and histochemical criteria. Contamination of each cell type with the other was less than 1%. Separated cells were grown on plastic or on Matrigel-coated Millicell inserts with nitrocellulose membranes. Transmission and scanning electron microscope analyses demonstrated the existence of tight junctions and prominent microvilli in the epithelial cultures on inserts but not on plastic. Asymmetrical secretion of prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E (PGE) by epithelial cells provided further evidence of polarization. Epithelial cell secretion of PGF2 alpha was greater than that by stromal cells whereas PGE secretion by stromal cells was greater than that by epithelial cells. Epithelial secretion in the basal direction was approximately 4 and 3 times that of apical secretion for PGF2 alpha and PGE, respectively. The separation protocol provides pure populations of ovine endometrial epithelial and stromal cells and the cultured epithelial cells exhibit characteristics of in vivo morphology and polarized function.


Palmar digital vein thromboses: their different expressions.
There have only been a few reports about thrombotic events in the volar digital veins. The observation of 2 such cases gives reason to discuss this rare symptomatology. Thrombosis of the digital veins can be categorised into three subtypes: the first shows clinical similarity to thrombotic events in veins or varicose veins of the limbs and may be related to a hypercoagulable state; the second group develops in a pre-existing normal vein or an acquired venous cavernoma and does not show clinical or histological signs of inflammation; the third category resembles Mondor's disease and may be named Mondor's phlebitis of the finger; histopathological examination has yet to be done. In any case of thrombosis of the volar digital veins, an inherited or acquired hypercoagulable state must be ruled out.


[Clinical features of obscure-overt gastrointestinal bleeding].
Obscure gastrointestinal bleeding (OGIB) is defined as recurrent acute or chronic bleeding for which no sources have been identified by routine endoscopic and contrast studies. The patients with OGIB are frequently difficult to manage and often undergo extensive investigation and even laparatomy without diagnosis. The aim of this study was to review our overall experiences of the investigation and treatment of OGIB. We reviewed, retrospectively, medical records of 41 cases with OGIB from June 1996 to July 2002. Of the 41 patients with OGIB, there were 21 men and 20 women and their mean age was 47.8 years (range, 18 to 81 years). Diagnosis was possible in 13 patients (31.7%) and no specific causes were identified in the remaining 28 patients (68.3%). The principal etiologies were gastrointestinal stromal tumor of the small bowel in 3 cases, duodenal diverticulum in 2 cases. Other causes are as follows: adenocarcinoma of the duodenal 3rd portion, duodenal varix at the 4th portion, splenic artery pseudoaneurysm, Crohn's disease, jejunal ulcer, ileal ulcer, ileal angiodysplasia, and anastomosis site bleeding after hemicolectomy. We conclude that further and logical diagnostic investigations such as small bowel enteroscopy and wireless capsule endoscopy will promise better results.


Avian Influenza A Viruses: Evolution and Zoonotic Infection.
Although efficient human-to-human transmission of avian influenza virus has yet to be seen, in the past two decades avian-to-human transmission of influenza A viruses has been reported. Influenza A/H5N1, in particular, has repeatedly caused human infections associated with high mortality, and since 1998 the virus has evolved into many clades of variants with significant antigenic diversity. In 2013, three (A/H7N9, A/H6N1, and A/H10N8) novel avian influenza viruses (AIVs) breached the animal-human host species barrier in Asia. In humans, roughly 35% of A/H7N9-infected patients succumbed to the zoonotic infection, and two of three A/H10N8 human infections were also lethal; however, neither of these viruses cause influenza-like symptoms in poultry. While most of these cases were associated with direct contact with infected poultry, some involved sustained human-to-human transmission. Thus, these events elicited concern regarding potential AIV pandemics. This article reviews the human incursions associated with AIV variants and the potential role of pigs as an intermediate host that may hasten AIV evolution. In addition, we discuss the known influenza A virus virulence and transmission factors and their evaluation in animal models. With the growing number of human AIV infections, constant vigilance for the emergence of novel viruses is of utmost importance. In addition, careful characterization and pathobiological assessment of these novel variants will help to identify strains of particular concern for future pandemics.


Gut microorganisms and cardiovascular disease: carnitine is the answer.
This short paper summarizes the current understanding regarding carnitine and gut bacteria which will provide new clues to uncover the background of multifactorial diseases such as cardiovascular disorders (CVD). Carnitine is a quaternary ammonium compound biosynthesized from phosphatidylcholine and the amino acids lysine and methionine (Fig. 3, Ref. 12).


Forced linear oscillations of microbubbles in blood capillaries.
A theoretical investigation of the forced linear oscillations of a gas microbubble in a blood capillary, whose radius is comparable in size to the bubble radius is presented. The natural frequency of oscillation, the thermal and viscous damping coefficients, the amplitude resonance, the energy resonance, as well as the average energy absorbed by the system, bubble plus vessel, have been computed for different kinds of gas microbubbles, containing air, octafluropropane, and perflurobutane as a function of the bubble radius and applied frequency. It has been found that the bubble behavior is isothermal at low frequencies and for small bubbles and between isothermal and adiabatic for larger bubbles and higher frequencies, with the viscous damping dominating over the thermal damping. Furthermore, the width of the energy resonance is strongly dependent on the bubble size and the natural frequency of oscillation is affected by the presence of the vessel wall and position of the bubble in the vessel. Therefore, the presence of the blood vessel affects the way in which the bubble absorbs energy from the ultrasonic field. The motivation of this study lies in the possibility of using gas microbubbles as an aid to therapeutic focused ultrasound treatments.


Nitric oxide and downstream second messenger cGMP and cAMP enhance adipogenesis in primary human preadipocytes.
Obesity is correlated with chronic low-grade inflammation. Thus the induction of inflammation could be used to stimulate adipose tissue formation in tissue-engineering approaches. As nitric oxide (NO) is a key regulator of inflammation, we investigated the effect of NO and its downstream signaling molecule guanosine 3',5'-cyclic monophosphate (cGMP) as well as adenosine 3',5'-cyclic monophosphate (cAMP) on preadipocytes in vitro. Preadipocytes were isolated from human subcutaneous adipose tissue, cultured until confluence, and differentiated. The NO donor diethylenetriamine (DETA)/NO (30-150 microm) was added during proliferation and differentiation. Additionally, cGMP/cAMP analogs 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP), 8-(4-chlorophenylthio)-guanosine 3',5'-cyclic monophosphate (8-pCPT-cGMP) and 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP), and the adenylyl cyclase activator forskolin, specific guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and adenylyl cyclase inhibitor 2'-5'-dideoxyadenosine (ddA), were applied. Proliferation and differentiation were evaluated. DETA/NO in combination with the standard differentiation procedure significantly enhanced maturation of precursor cells to adipocytes. Proliferation, in contrast, was inhibited in the presence of NO. The application of cGMP and cAMP, respectively, increased pre-adipocyte differentiation to an even higher extent than NO. Inhibitors of the underlying pathways caused a significant decrease in adipogenic conversion. Our results support the application of NO donors during transplantation of preadipocytes in a 3-dimensional setting to accelerate and optimize differentiation. The results suggest that, instead of the rather instable and reactive molecule NO, the application of cGMP and cAMP would be even more effective because these substances have a stronger adipogenic effect on preadipocytes and a longer half-life than NO. Also, by applying inhibitors of the underlying pathways, the induced inflammatory condition could be regulated to the desired level.


Feminization of Male Mouse Liver by Persistent Growth Hormone Stimulation: Activation of Sex-Biased Transcriptional Networks and Dynamic Changes in Chromatin States.
Sex-dependent pituitary growth hormone (GH) secretory profiles-pulsatile in males and persistent in females-regulate the sex-biased, STAT5-dependent expression of hundreds of genes in mouse liver, imparting sex differences in hepatic drug/lipid metabolism and disease risk. Here, we examine transcriptional and epigenetic changes induced by continuous GH infusion (cGH) in male mice, which rapidly feminizes the temporal profile of liver STAT5 activity. cGH repressed 86% of male-biased genes and induced 68% of female-biased genes within 4 days; however, several highly female-specific genes showed weak or no feminization, even after 14 days of cGH treatment. Female-biased genes already in an active chromatin state in male liver generally showed early cGH responses; genes in an inactive chromatin state often responded late. Early cGH-responsive genes included those encoding two GH/STAT5-regulated transcriptional repressors: male-biased BCL6, which was repressed, and female-specific CUX2, which was induced. Male-biased genes activated by STAT5 and/or repressed by CUX2 were enriched for early cGH repression. Female-biased BCL6 targets were enriched for early cGH derepression. Changes in sex-specific chromatin accessibility and histone modifications accompanied these cGH-induced sex-biased gene expression changes. Thus, the temporal, sex-biased gene responses to persistent GH stimulation are dictated by GH/STAT5-regulated transcription factors arranged in a hierarchical network and by the dynamics of changes in sex-biased epigenetic states.


The fluoroquinolones exert a reduced rate of kill against Enterococcus faecalis.
The bactericidal activities of ciprofloxacin, ofloxacin and DR-3355 have been investigated against Enterococcus faecalis, Staphylococcus aureus and Staphylococcus epidermidis over 24 h. The three fluoroquinolones were found to be rapidly bactericidal against the staphylococci, killing over 99% of the bacteria during the first 3 h of exposure with a further reduction in viability of approximately one logarithm occurring over the next 21 h. In contrast, the fluoroquinolones displayed a much slower rate of kill against E. faecalis, as little or no bactericidal activity was detected over the first 3 h for both E. faecalis ATCC19433 and a clinical isolate. At 6 h all three of the drugs were bactericidal against the enterococci although the amount of kill was not as great as against the staphylococci. However, at 24 h the amount of kill obtained with all three drugs was similar to that obtained for staphylococci exposed to these drugs. Ciprofloxacin, ofloxacin and DR-3355 were not active against E. faecalis ATCC19433 in phosphate buffered saline and therefore require cell division for their bactericidal activity against this species.


Assessment of facial features with a range camera.
We describe a new method for the quantitative analysis of facial features using a range camera with a three-dimensional measuring program. The range camera consists of a video camera, a light projector, and a computer. The video camera captures a number of images of different light patterns projected on to the face. From these, a "range image" is computed. One fully illuminated intensity image of the face is also taken. By defining anatomical landmarks manually on the intensity image, three-dimensional measurements are automatically obtained from corresponding positions in the range image. The method is highly accurate and precise, and is a simple and reliable way of assessing facial features. We recommend that the system be adapted in clinical practice--for example, in diagnosing syndromes and planning plastic and reconstructive surgery.


Current oral agents for type 2 diabetes. Many options, but which to choose when?
Increasingly, type 2 diabetes takes a toll on public health and healthcare costs in the United States. Although the remedy for this growing problem is very complex, two critical components of its control are prevention and effective therapy. Progress in diabetes prevention is likely to take decades. But fortunately, growth in our understanding of what occurs in this chronic disease has led to advances in the pharmacologic options aimed at decreasing hyperglycemia, the main clinically measurable metabolic consequence of diabetes. In this article, Drs Ahmann and Riddle provide an overview of the oral agents now available for the treatment of diabetes and discuss the clinical factors that help determine when to use which medication and what outcome to expect.


irRECIST for the Evaluation of Candidate Biomarkers of Response to Nivolumab in Metastatic Clear Cell Renal Cell Carcinoma: Analysis of a Phase II Prospective Clinical Trial.
Immune-related RECIST (irRECIST) were designed to capture atypical responses seen with immunotherapy. We hypothesized that, in patients with metastatic clear cell renal cell carcinoma (mccRCC), candidate biomarkers for nivolumab response would show improved association with clinical endpoints capturing atypical responders (irRECIST) compared with standard clinical endpoints (RECISTv1.1). Endpoints based on RECISTv1.1 [objective response rate (ORR)/progression-free survival (PFS)] or irRECIST [immune-related ORR (irORR)/immune-related PFS (irPFS)] were compared in patients enrolled in the CheckMate-010 trial. Pretreatment tumors were analyzed by PD-L1 and PD-L2 IHC, and by multiplex immunofluorescence for CD8, PD-1, TIM-3, and LAG-3. T-cell activation signatures were assessed by RNA sequencing. Median irPFS was significantly longer than median PFS. irORR was not significantly different from ORR, but immune-related progressive disease (irPD) rate was significantly lower than progressive disease (PD) rate. Tumor cell (TC) PD-L1 expression was not associated with PFS or ORR, but patients with TC PD-L1 ≥1% had longer median irPFS and higher irORR. High percentage of CD8+ tumor-infiltrating cells (TIC) that are PD-1+TIM-3-LAG-3- (% CD8+PD-1+TIM-3-LAG-3- TIC) correlated with high levels of T-cell activation and was associated with longer median irPFS and higher irORR. Notably, combination of TC PD-L1 expression with % CD8+PD-1+TIM-3-LAG-3- TIC identified three groups of patients for which irPFS and irORR were significantly different. Atypical responders to nivolumab were identified in the CheckMate-010 trial. We observed improved association of candidate biomarkers for nivolumab response with endpoints defined by irRECIST compared with RECISTv1.1. TC PD-L1 expression in combination with PD-1 expression on CD8+ TIC may predict outcome on nivolumab in mccRCC.


A Comprehensive Review of the Main Lignan Components of Schisandra chinensis (North Wu Wei Zi) and Schisandra sphenanthera (South Wu Wei Zi) and the Lignan-Induced Drug-Drug Interactions Based on the Inhibition of Cytochrome P450 and P-Glycoprotein Activities.
Wu Wei Zi is the dried fruit of Schisandra chinensis (Turcz.) Baill. or Schisandra sphenanthera Rehd. et Wils. (family Magnoliaceae). As a homology of medicine and food, it has been widely used in China for thousands of years, to tonify the kidney, and ameliorate neurological, cardiovascular, liver, and gastrointestinal disorders. As its increasing health benefits and pharmacological value, many literatures have reported that the combination of Wu Wei Zi in patients has led to fluctuations in the blood level of the combined drug. Therefore, it is extremely important to evaluate its safety concern such as drug-drug interactions (DDIs) when patients are under the poly-therapeutic conditions. This review summarized the effects of Wu Wei Zi extract and its major lignan components on cytochrome P450 and P-glycoprotein activities, the change of which could induce metabolic DDIs. Our review also elaborated on the differences of the major lignan components of the two Schisandra species, as well as the absorption, distribution, metabolism, and elimination of the major lignans. In conclusion, these results would enhance our understanding of the DDI mechanisms involving Wu Wei Zi, and may potentially untangle some differing and conflicting results in the future.


Role of toxigenic and invasive bacteria in acute diarrhea of childhood.
The cause of pediatric diarrhea in Brazil was investigated with use of assays for toxigenic and invasive bacteria. Potential etiologic agents were identified in 31 of 40 consecutive children with diarrhea: toxigenic Escherichia coli or klebsiella in 20 patients (50 per cent); invasive Esch, coli or salmonella in four (10 per cent), and both toxigenic and invasive organisms in seven (18 per cent). Fecal leukocytes were present in nine of the 11 patients (82 per cent) with invasive pathogens. All 27 patients with toxigenic isolates had organisms that produced heat-labile cholera-like toxin; three patients had Esch. coli that also produced a heat-stable toxin. Among 20 controls without diarrhea there were no organisms that produced heat-labile toxin or tissue invasion, but there was one Esch. coli that produced only heat-stable toxin and one salmonella. In this pediatric population Esch. coli appears to cause most acute diarrheas due to toxigenic and invasive pathogenic mechanisms.


Candida dubliniensis fungemia and vascular access infection.
Candida dubliniensis is a newly recognized species of yeast, which may have been forrmerly identified as Candida albicans, that has been rarely isolated from invasive fungal infections among humans. The authors document a C. dubliniensis fungemia that occurred during the course of a vascular access infection in a 2-year-old who was undergoing active therapy for neuroblastoma. Presumptive C. albicans isolates from an 18-year period were reassessed, and it was found that C. dubliniensis is a rare cause of fungemia among pediatric patients (0.5% of all such isolates).


Understanding adaptive motor control of the paretic upper limb early poststroke: the EXPLICIT-stroke program.
During upper limb motor recovery after stroke, the greatest improvements occur typically in the first 5 weeks poststroke. It is unclear what patients learn during this early phase of recovery. To investigate the hypothesis that, early poststroke, patients learn to master the degrees of freedom in the paretic upper limb as reflected by dissociated shoulder and elbow movements during reach-to-grasp. Thirty-one patients with a first-ever ischemic stroke were included. Repeated 3-dimensional kinematic measurements were conducted at 14, 25, 38, 57, 92, and 189 days poststroke. Trunk, shoulder, elbow, and wrist rotations were measured during a reach-to-grasp task. Using principal component analysis the longitudinal changes in dissociated upper limb movements during reach-to-grasp were investigated. Twelve healthy subjects were included for comparison. The main coordination pattern during reach-to-grasp in patients with stroke and healthy subjects consisted mostly of horizontal shoulder adduction and elbow extension. The standard deviation of this main pattern increased over time, with the largest increase in the first 5 weeks poststroke (F = 5.5, P < .001), but remained smaller than in healthy individuals. The standard deviation increased by 0.46° per day between 14 and 38 days and tapered off to 0.05° per day between 38 and 189 days poststroke. Our results suggest that restitution of motor control by dissociation of shoulder and elbow movements occurs mainly early poststroke. However, compared with healthy adults, most patients did not achieve fully dissociated upper limb movements at 26 weeks poststroke, suggesting that upper limb motor control after stroke remains adaptive.


The structure of Escherichia coli signal recognition particle revealed by scanning transmission electron microscopy.
Structural studies on various domains of the ribonucleoprotein signal recognition particle (SRP) have not converged on a single complete structure of bacterial SRP consistent with the biochemistry of the particle. We obtained a three-dimensional structure for Escherichia coli SRP by cryoscanning transmission electron microscopy and mapped the internal RNA by electron spectroscopic imaging. Crystallographic data were fit into the SRP reconstruction, and although the resulting model differed from previous models, they could be rationalized by movement through an interdomain linker of Ffh, the protein component of SRP. Fluorescence resonance energy transfer experiments determined interdomain distances that were consistent with our model of SRP. Docking our model onto the bacterial ribosome suggests a mechanism for signal recognition involving interdomain movement of Ffh into and out of the nascent chain exit site and suggests how SRP could interact and/or compete with the ribosome-bound chaperone, trigger factor, for a nascent chain during translation.


Effects of perioperative glycemic indicators on outcomes of endovascular treatment for vertebrobasilar artery occlusion.
Endovascular treatment (EVT) is, to date, the most promising treatment of vertebrobasilar artery occlusion (VBAO). The study aimed to determine the influence of perioperative glucose levels on clinical outcomes in patients with acute VBAO treated with EVT. We retrospectively collected consecutive VBAO patients received EVT in 21 stroke centers in China. The associations between perioperative glycemic indicators (including fasting blood glucose[FBG], admission hyperglycemia, stress hyperglycemia ratio [SHR] and short-term glycemic variability [GV]) and various clinical outcomes were analyzed in all patients and subgroups stratified by diabetes mellitus (DM). A total of 569 patients were enrolled. Admission hyperglycemia significantly correlated with increased risk of symptomatic intracranial hemorrhage (sICH) (odds ratio [OR] 3.24, 95% confidence interval [CI]: 1.40-7.46), poor functional outcomes at 90 days (OR 1.91, 95%CI: 1.15-3.18) and 1 year (OR 1.96, 95%CI: 1.20-3.22). Similar significant correlations exist between FBG, SHR, GV and all the adverse outcomes except higher levels GV was not associated with increased risk of sICH (OR 1.04, 95% CI: 0.97-1.12). Subgroup analyses showed that admission hyperglycemia, FBG and SHR were significantly associated with adverse outcomes in non-diabetic patients, but not in DM patients. While, GV was associated with poor functional outcomes regardless of diabetes history. Admission hyperglycemia, FBG, SHR and short-term GV in VBAO patients treated with EVT were associated with adverse outcomes. The results suggested that comprehensive evaluation and appropriate management of perioperative glucose might be important for patients with VBAO and treatment with EVT.


Receptors involved in the positive inotropic action induced by dopamine on the ventricle of a 7-day-old chick embryo heart.
Earlier experiments only revealed involvement of sympathetic pre-synaptic dopaminergic receptors in dopamine induced inotropism in myocardium. We therefore used electrically stimulated (1 Hz) isolated 7-day-old chick embryo heart ventricles, thought to be devoid of functional sympathetic nerves, to re-investigate post-synaptic receptors involvement and particularly that of dopaminergic receptors in the positive inotropic effect of dopamine. The results showed that noradrenaline, isoprenaline and dopamine produced a positive inotropic effect with a similar efficacy and with an order of potency as follows: Isoprenaline = Noradrenaline > Dopamine. Tyramine induced no significant modification of the "initial tension" indicating that functional sympathetic innervation and/or releasable endogenous catecholamines were not demonstrable in the 7-day-old chick embryo heart ventricle. Propranolol (1 microM) competitively antagonized the positive inotropic response to isoprenaline, noradrenaline and dopamine, meanwhile phentolamine (3 microM) failed to significantly modify the effects of both noradrenaline and dopamine, indicating that these catecholamines induced their positive inotropic effects via stimulation of beta-adrenoceptors; involvement of alpha-adrenergic receptors stimulation was not demonstrable in these effects. Moreover, haloperidol (2 microM) antagonized the positive inotropic response to dopamine but had not any significant effect on the response to isoprenaline. The combined application of both propranolol and haloperidol antagonized the positive inotropic response to dopamine to a greater extent than when these two antagonists were given alone. Consequently, post-synaptic dopaminergic receptors were also involved in the positive inotropic effect of dopamine. Furthermore, in preparations in which sodium channels were inactivated by high potassium physiological salt solution, high concentrations of dopamine (0.1 mM to 1 mM) induced a slow developing electrical and positive inotropic responses which were also inhibited by propranolol and haloperidol, but not by phentolamine. These latter results indicated that like beta-adrenergic stimulation, the slow inward calcium current activated by stimulation of adenylate cyclase, was at least in part involved in the positive inotropic response to dopamine. In conclusion, dopamine induced its positive inotropism via stimulation of post-synaptic beta-adrenergic and dopaminergic receptors. The contribution of dopaminergic receptors in this positive inotropic effect might be of the DA-2 receptors since haloperidol used had been reported to be more DA-2 than DA-1 antagonist. These DA-2 receptors subtypes would mediate activation of adenylate cyclase.


[PROGRESS OF ALGINATE DERIVATIVES BASED ON BIOMEDICAL MATERIALS].
To summarize the current research status of alginate derivatives based on biomedical materials, and analyze several key points as novel clinical products. The general preparation and application methods of alginate derivatives based on biomedical materials at home and abroad were reviewed. The present status and problems were analyzed. The derivation methods to prepare alginate derivatives include crosslink, sulfation, biological factors derivatization, hydrophobic modification, and graft copolymerization. With excellent bionic performance of structure and properties, many alginate derivatives are available for tissue engineering scaffolds, artificial organs, and drug delivery systems etc. However, more systematic applied basic research data should be collected and statistically analyzed for risk managements. Alginate derivatives have good feasibility as novel medical products, meanwhile, systematic evaluation and verification should be executed for their safety, effectiveness, and suitability.


Equine bronchial epithelial cells are susceptible to cell entry with a SARS-CoV-2 pseudovirus but reveal low replication efficiency.
To examine the susceptibility of cultured primary equine bronchial epithelial cells (EBECs) to a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus relative to human bronchial epithelial cells (HBECs). Primary EBEC cultures established from healthy adult horses and commercially sourced human bronchial epithelial cells (HBECs) were used as a positive control. Angiotensin-converting enzyme 2 (ACE2) expression by EBECs was demonstrated using immunofluorescence, western immunoblot, and flow cytometry. EBECs were transduced with a lentivirus pseudotyped with the SARS-CoV-2 spike protein that binds to ACE2 and expresses the enhanced green fluorescent protein (eGFP) as a reporter. Cells were transduced with the pseudovirus at a multiplicity of infection of 0.1 for 6 hours, washed, and maintained in media for 96 hours. After 96 hours, eGFP expression in EBECs was assessed by fluorescence microscopy of cell cultures and quantitative PCR. ACE2 expression in EBECs detected by immunofluorescence, western immunoblotting, and flow cytometry was lower in EBECs than in HBECs. After 96 hours, eGFP expression in EBECs was demonstrated by fluorescence microscopy, and mean ΔCt values from quantitative PCR were significantly (P < .0001) higher in EBECs (8.78) than HBECs (3.24) indicating lower infectivity in EBECs. Equine respiratory tract cells were susceptible to cell entry with a SARS-CoV-2 pseudovirus. Lower replication efficiency in EBECs suggests that horses are unlikely to be an important zoonotic host of SARS-CoV-2, but viral mutations could render some strains more infective to horses. Serological and virological monitoring of horses in contact with persons shedding SARS-CoV-2 is warranted.


[The non-medicamentous methods for the prevention and treatment of the patients presenting with neurocirculatory asthenia and concomitant enhanced meteosensitivity].
The relevance of the problem stated in the title of this article comes from the significant increase in the prevalence of the functional cardiovascular disorders having been documented during the past years especially such as circulatory asthenia that most frequently affects the young people of the working age suffering from the systemic neurogenic imbalance in the organism and can be seriously aggravated by the influence of biotropic weather conditions and be responsible for enhanced meteosensitivity that has negative effect on the quality of life and impairs the effectiveness of the therapeutic interventions. The objective of the present study was to provide the scientifically sound substantiation of the feasibility of the application of the non-medicamentous methods (including the interval hypoxic training and «dry» carbonic baths) for the prevention and treatment of neurocirculatory asthenia complicated by enhanced meteosensitivity and evaluate the therapeutic effectiveness of these approach. A total of 50 patients with the verified diagnosis of neurocirculatory asthenia were recruited to participate in the study. All the patients were divided into two groups. 62% of them exhibited the well apparent meteosensitivity and were included in the study group 1. Group 2 was comprised of the remaining patients (38% of their total number) presenting with neurocirculatory asthenia who did not suffer appreciable changes in the general physical and mental state under the influence of varying weather conditions. The patients of both groups received the identical combined treatment consisting of interval hypoxic training and taking «dry» carbonic baths. Monitoring of the main meteorological parameters was carried out on a daily basis. It was combined with the assessment of the weather conditions from the medical perspective, the evaluation of the physical performance capability of the patients based on the results of the veloergometric testing, and the estimation of their functional state of the autonomous nervous system with the use of the data obtained in cardiointervalographic studies. In addition, the state of the microcirculatory system was evaluated by means of laser Doppler flowmetry and making use of a capillary blood flow analyzer. The psychological status of the patients was characterized using a computer-generated version of the abridged multifactorial questionnaire for the elucidation of the manifest personality-scale anxiety (Spielbeger's State-Trait Anxiety Inventory). All these studies were carried out both before and after the course of non-medicamentous therapy. After the course of the combined non-medicamentous treatment had been completed the health status of the patients comprising the two groups was found to be improved as appeared from the decrease of the number and severity of subjective autonomous manifestations, the positive changes in the functional state of the cardiovascular system and the autonomic nervous system as well as in the general psychological status. The most clinically significant result of the treatment included the reduction in the incidence of the severe meteopathic reactions in the patients of group 2 (from 14% before to 3% after therapy). The frequency of moderately expressed meteopathic reactions likewise decreased (from 31% before to 14% after the treatment). The study has demonstrated that under the environmental and climatic conditions of the of Moscow region formation of biotropic weather factors of the hypoxic type (39%) constitutes a serious risk factor contributing to the development of imbalance in the vegetative nervous system and its exacerbations in response to variations of weather parameters. The application of the non-medicamentous therapeutic modalities (including interval hypoxic training and «dry» carbonic baths) for the management of the meteosensitive patients presenting with neurocirculatory asthenia is pathogenetically justified, and they can be recommended for both the treatment and prevention of weather- dependent pathological processes and their exacerbations.


Universal critical power for nonlinear Schrödinger equations with a symmetric double well potential.
Here we consider stationary states for nonlinear Schrödinger equations in any spatial dimension n with symmetric double well potentials. These states may bifurcate as the strength of the nonlinear term increases and we observe two different pictures depending on the value of the nonlinearity power: a supercritical pitchfork bifurcation, and a subcritical pitchfork bifurcation with two asymmetric branches occurring as the result of saddle-node bifurcations. We show that in the semiclassical limit, or for a large barrier between the two wells, the first kind of bifurcation always occurs when the nonlinearity power is less than a critical value; in contrast, when the nonlinearity power is larger than such a critical value then we always observe the second scenario. The remarkable fact is that such a critical value is a universal constant in the sense that it does not depend on the shape of the double well potential and on the dimension n.


The effect of transportation of broilers during summer on the expression of heat shock protein 70, postmortem metabolism and meat quality.
The objective of this study was to determine the effects of different transport times on broilers during summer on stress, meat quality, and early postmortem muscle metabolites. Arbor Acres broiler chickens (n = 105) were randomly categorized into 5 treatments: unstressed control, 0.5 h, 1 h, 2 h, and 4 h transport. Each treatment consisted of 3 replicates with 7 birds each. All birds (except the control group) were transported according to a designed protocol. With the extension of transport time, the activities of plasma creatine kinase (CK) and lactate dehydrogenase (LDH) gradually increased. The content of heat shock protein 70 (Hsp70) did not change significantly during 0.5 h transport compared to the control group, but was significantly higher (P < 0.05) at 1 h or more of transport time. Also, transport times of 2 h or more resulted in a death rate of 20%-33% of broilers. We found that the breast meat in the 0.5 h transport group had significantly (P < 0.05) higher L* values, drip loss, cooking loss, AMP/ATP ratio, and phosphorylation of AMP-activated protein kinase (p-AMPK). In addition, pH24h was lower compared to the control group, increasing the likelihood of pale, soft, and exudative (PSE)-like meat. However, no significant variations were found in meat color, drip loss, or cooking loss in other transport groups compared to the control group under the condition of this study. Muscle glycogen content decreased with time of transportation. There were significant correlations among p-AMPK and meat quality (P < 0.05). These results indicate that preslaughter transport during summer may cause severe physiological and biochemical changes of broilers. Further investigations studying the deeper relationship between biological indicators and meat quality according to the similar transport conditions would provide a better understanding of the effect of transport duration on meat quality.


MAPKAPK2, a potential dynamic network biomarker of α-synuclein prior to its aggregation in PD patients.
One of the important pathological features of Parkinson's disease (PD) is the pathological aggregation of α-synuclein (α-Syn) in the substantia nigra. Preventing the aggregation of α-Syn has become a potential strategy for treating PD. However, the molecular mechanism of α-Syn aggregation is unclear. In this study, using the dynamic network biomarker (DNB) method, we first identified the critical time point when α-Syn undergoes pathological aggregation based on a SH-SY5Y cell model and found that DNB genes encode transcription factors that regulated target genes that were differentially expressed. Interestingly, we found that these DNB genes and their neighbouring genes were significantly enriched in the cellular senescence pathway and thus proposed that the DNB genes HSF1 and MAPKAPK2 regulate the expression of the neighbouring gene SERPINE1. Notably, in Gene Expression Omnibus (GEO) data obtained from substantia nigra, prefrontal cortex and peripheral blood samples, the expression level of MAPKAPK2 was significantly higher in PD patients than in healthy people, suggesting that MAPKAPK2 has potential as an early diagnostic biomarker of diseases related to pathological aggregation of α-Syn, such as PD. These findings provide new insights into the mechanisms underlying the pathological aggregation of α-Syn.


Awareness, use and perceptions about E-cigarettes among adult smokers in Karachi, Pakistan.
To estimate the prevalence of awareness, current use and intention to use of e-cigarettes among adult smokers. This cross-sectional survey was carried out at the Aga Khan University Hospital, Karachi, from July to August 2016, and comprised people aged above 18 years who had smoked more than 100 cigarettes in their lifetime. Convenience sampling method was used. A self-administered questionnaire was used to collect data. SPSS 22 was used for data analysis.. Of the 387 participants, 359(92.8%) were male. The overall mean age was 32.4±12.6 years. Moreover, 215(55.5%) respondents belonged to the middle socio-economic class. Besides, 249(64.3%) respondents were aware of e-cigarettes while 39(10.1%) used them, and 81(20.9%) wanted to use them. Socio-economic status was the best predictor for awareness about e-cigarettes (p<0.001), while gender (p=0.001), occupation<lt;0.001) and current smoking status (p=0.009) were significantly associated with the use of e-cigarettes. E-cigarettes were perceived as less harmful than tobacco cigarettes by 175(45.3%) respondents, helpful in quitting smoking by 138(35.6%), associated with chronic diseases by 158(40.9%), addictive 142(36.7%), and not safe during pregnancy by 197(50.8%) participants. The percentage of e-cigarette usage was low despite the higher than expected awareness among the subjects.


Recent advances in Philadelphia chromosome-positive malignancies: the potential role of arsenic trioxide.
Chronic myelogenous leukemia (CML) is characterized by the presence of the Bcr-Abl fusion gene, which encodes a constitutively active tyrosine kinase that has been strongly implicated as the sole oncogenic abnormality in early-stage CML. Treatment with the specific tyrosine kinase inhibitor imatinib mesylate has achieved excellent results in CML, at all stages of the disease. However, limitations to the successful use of imatinib mesylate as a single agent include the problem of resistance, seen chiefly in patients with advanced-phase disease. This review summarizes the clinical results to date with imatinib mesylate and briefly discusses the problem of resistance before describing potential strategies, including the use of combination therapy. In particular, the rationale for combination therapy with arsenic trioxide will be examined.


Treatment of a ruptured shallow trilobed cerebral aneurysm with the novel saccular endovascular aneurysm lattice (SEAL) device: A case report with one year follow-up.
Intrasaccular flow disruption is a viable alternative to other endovascular treatments for saccular or wide-necked bifurcation intracranial aneurysms; however, wide neck aneurysms with irregular shapes or shallow depth may not be amenable to treatment currently available intrasaccular devices. Here, we present the first ever case report of the novel Saccular Endovascular Aneurysm Lattice Embolization System (SEAL™). The versatile utility of the SEAL™ device is demonstrated in a patient with acute subarachnoid hemorrhage (SAH) from a ruptured, complex, left middle cerebral artery (MCA) trilobed shallow wide-necked bifurcation aneurysm. Deployment and implantation of the SEAL device were technically feasible, safe, and conformed well to the irregular shape of the complex, ruptured aneurysm. Immediate total aneurysm occlusion was observed after implantation. Importantly, 1-year angiographic follow-up demonstrated durable, complete occlusion with no safety concerns. The SEAL device is a promising new novel technology which has the potential to treat very shallow aneurysms with limited height and irregular, multilobulated aneurysms.


Preparation, physical-chemical characterisation and cytocompatibility of calcium carbonate cements.
The feasibility of calcium carbonate cements involving the recrystallisation of metastable calcium carbonate varieties has been demonstrated. Calcium carbonate cement compositions presented in this paper can be prepared straightforwardly by simply mixing water (liquid phase) with two calcium carbonate phases (solid phase) which can be easily obtained by precipitation. An original cement composition was obtained by mixing amorphous calcium carbonate and vaterite with an aqueous medium. The cement set and hardened within 2h at 37 degrees C in an atmosphere saturated with water and the final composition of the cement consisted mostly of aragonite. The hardened cement was microporous and showed poor mechanical properties. Cytotoxicity tests revealed excellent cytocompatibility of calcium carbonate cement compositions. Calcium carbonates with a higher solubility than the apatite formed for most of the marketed calcium phosphate cements might be of interest to increase biomedical cement resorption rates and to favour its replacement by bone tissue.


[Occupational tuberculosis in Slovakia and in the Czech Republic].
To conduct a retrospective 15-year study to monitor trends in the number of employees at risk for occupational tuberculosis (TB) (levels III and IV) in the Slovak Republic, and in particular in the sector of economic activities Q (health care and social assistance). Furthermore, to analyze reported cases of occupational TB and to compare the incidence and sex-specific and age-specific prevalence with the data reported in the Czech Republic. Data on the number of employees at risk of exposure to occupational TB were derived from the Automated Risk Classification System of the Slovak Republic. Data on cases of occupational TB were taken from health statistics (Institute of Health Information and Statistics/National Health Information Center in the Slovak Republic and the National Institute of Public Health in the Czech Republic). A retrospective analysis was conducted (for 1998-2012) of reported cases of occupational TB, selected from Article 24 of the List of occupational diseases (infectious and parasitic diseases except tropical infectious and parasitic diseases and diseases transmissible from animals to humans). The selection criterion was a TB diagnosis according to ICD-10. In the Czech Republic, the data were derived from Article 5.1.02 (tuberculosis), Chapter V. of the List of Occupational Diseases. The data obtained were analyzed by methods of descriptive statistics. The numbers of employees with a level III risk of exposure to occupational TB in the Slovak Republic declined by 30% over the 15 years of study and by 40% in category Q. In 2012, 2027 employees were classified in category III and 1442 of them belonged to group Q. Females accounted for 81-84% of employees at risk of exposure to occupational TB. Eighty-six and 181 cases of occupational TB were reported in the Slovak Republic and in the Czech Republic, respectively, in 1998-2012, with the incidence showing a downward trend in both countries. TB of the respiratory tract was reported most often (83.7% of the total of reported cases of occupational TB). As expected, more cases occurred in females than in males (1.9 times as many cases in females as in males in the Slovak Republic and three times as many cases in females as in males in the Czech Republic). The incidence of occupational TB was the highest in sector Q, with the highest absolute numbers reported in nurses. In 2012, the incidence rates of occupational TB were 0.22 cases per 100,000 sick benefit policy holders in the Slovak Republic and 0.13 cases per 100,000 sick benefit policy holders in the Czech Republic. The incidence of occupational TB has a downward trend in both countries, similarly to TB incidence in the general population. A negative aspect in both countries is the incidence of occupational TB at the middle productive age, in contrast to the population occupationally non-exposed to TB. Slovakia is surrounded by higher prevalence countries, with the exception of the Czech Republic. It cannot be ruled out that, in addition to the known factors influencing the prevalence of TB, including occupational TB, migration from eastern countries, including job search migration, can also play a role in increase in TB cases. It is vital to continue epidemiological surveillance and to reduce the risk of TB as much as possible also in healthcare settings by adhering to barrier nursing practices. Cases of active TB need early and adequately long, controlled treatment in order to reduce, among others, the incidence of multi-drug resistant TB.


Selective proliferation of lymphoid cells from lineage-c-Kit+ Sca-1+ cells by a clonal bone marrow stromal cell line.
To understand the regulatory mechanisms involved in the development of hematopoietic stem cells, we cultured lineage-negative, c-Kit+ Sca-1+ stem cells sorted from bone marrow cells by a fluorescence-activated cell sorter (FACS) on layers of bone marrow stromal cell lines established from SV40 T-antigen gene transgenic mice. We previously reported that the TBR59 stromal cell line induced two sequential cobblestone formations: the first formation committed to the myeloid and the second to the lymphoid lineage. After examination of many other bone marrow stromal cell lines, we found that TBR31-1 stromal cells supported only lymphoid development of the sorted stem cells. The sorted stem cells proliferated by forming cobblestones and the cells were released from the cobblestones. Most released cell populations were B220-positive lymphoid cells; cell production continued for 2 months. Addition of G-CSF or M-CSF produced only a slight effect on myeloid development. FACS analysis of the released cells showed that the B-lymphoid-committed progenitors developed into mature B-cells by expressing surface immunoglobulin M. These results indicate that TBR31-1 bone marrow stromal cells selectively support B-lymphoid development, whereas TBR59 cells support both myeloid and lymphoid development of stem cells.


New Jersey Pharmacists' Perceptions on Performing COVID-19 Testing in Community Pharmacy Practice Sites.
BackgroundPoint of care testing (POCT) for Coronavirus Disease 2019 (COVID-19) is a major source of its control. On May 13, 2020, NJ pharmacists were authorized to order and perform COVID-19 testing, expanding their role in the response to the COVID-19 pandemic. Objective: The purpose of this study was to evaluate NJ pharmacists' perceptions on the safety and potential consequences of performing COVID-19 testing within their community pharmacy practice sites. Methods: An electronic survey was distributed to NJ-registered pharmacists approximately 3 months after the administrative order was issued. Results: The survey was completed by 523 recipients (3.39% response rate) and responses from 311 NJ pharmacists practicing in community pharmacy were analyzed. The majority of respondents (83.8%) were not providing testing, while 16.2% were testing at the time of survey distribution. Most testing pharmacists were staff pharmacists with one to five years of experience, working in a pharmacy chain approximately 30-40 hours per week. Those not testing identified lack of a pharmacy drive-through, insufficient staff, and potential workflow disruption as reasons for not testing. Increased workload and fear of spreading the virus to others were concerns noted by both testers and non-testers. Conclusion: Overall, NJ pharmacists reported mixed perceptions regarding performing COVID-19 testing. Challenges and barriers to pharmacist COVID-19 testing, including inadequate staffing and space, and concerns about reimbursement and disruption to workflow were identified. Findings may serve as a guide to design and implement strategies to overcome barriers.


Traumatic brain injury elevates glycogen and induces tolerance to ischemia in rat brain.
Previous studies have demonstrated that traumatic brain injury (TBI) increases the vulnerability of the brain to an acute episode of hypoxia-ischemia. The objective of the present study was to determine whether TBI alters the vulnerability of the brain to a delayed episode of ischemia and, if so, to identify contributing mechanisms. Sprague-Dawley rats were subjected to lateral fluid-percussion (FP) brain injury (n = 14) of moderate severity (2.3-2.5 atm), or sham-injury (n = 12). After recovery for 24 h, all animals underwent an 8-min episode of forebrain ischemia, followed by survival for 6 days. Ischemic damage in the hippocampus and cerebral cortex of the FP-injured hemisphere was compared to that in the contralateral hemisphere and to that in sham-injured animals. Remarkably, the number of surviving CA(1) neurons in the middle and lateral segments of the hippocampus in the FP-injured hemisphere was significantly greater than that in the contralateral hemisphere and sham-injured animals (p < 0.05). Likewise, in the cerebral cortex the number of damaged neurons tended to be lower in the FP-injured hemisphere than in the contralateral hemisphere. These results suggest that TBI decreased the vulnerability of the brain to a delayed episode of ischemia. To determine whether TBI triggers protective metabolic alterations, glycogen levels were measured in cerebral cortex and hippocampus in additional animals 24 h after FP-injury (n = 13) or sham-injury (n = 7). Cortical glycogen levels in the ipsilateral hemisphere increased to 12.9 +/- 6.4 mmol/kg (mean +/- SD), compared to 6.4 +/- 1.8 mmol/kg in the opposite hemisphere and 5.7 +/- 1.3 mmol/kg in sham-injured animals (p < 0.001). Similarly, in the hippocampus glycogen levels in the FP-injured hemisphere increased to 13.4 +/- 4.9 mmol/kg, compared to 8.1 +/- 2.4 mmol/kg in the contralateral hemisphere (p < 0.004) and 6.2 +/- 1.5 mmol/kg in sham-injured animals (p < 0.001). These results demonstrate that TBI triggers a marked accumulation of glycogen that may protect the brain during ischemia by serving as an endogenous source of metabolic energy.


Comprehensive framework for visualizing and analyzing spatio-temporal dynamics of racial diversity in the entire United States.
The United States is increasingly becoming a multi-racial society. To understand multiple consequences of this overall trend to our neighborhoods we need a methodology capable of spatio-temporal analysis of racial diversity at the local level but also across the entire U.S. Furthermore, such methodology should be accessible to stakeholders ranging from analysts to decision makers. In this paper we present a comprehensive framework for visualizing and analyzing diversity data that fulfills such requirements. The first component of our framework is a U.S.-wide, multi-year database of race sub-population grids which is freely available for download. These 30 m resolution grids have being developed using dasymetric modeling and are available for 1990-2000-2010. We summarize numerous advantages of gridded population data over commonly used Census tract-aggregated data. Using these grids frees analysts from constructing their own and allows them to focus on diversity analysis. The second component of our framework is a set of U.S.-wide, multi-year diversity maps at 30 m resolution. A diversity map is our product that classifies the gridded population into 39 communities based on their degrees of diversity, dominant race, and population density. It provides spatial information on diversity in a single, easy-to-understand map that can be utilized by analysts and end users alike. Maps based on subsequent Censuses provide information about spatio-temporal dynamics of diversity. Diversity maps are accessible through the GeoWeb application SocScape (http://sil.uc.edu/webapps/socscape_usa/) for an immediate online exploration. The third component of our framework is a proposal to quantitatively analyze diversity maps using a set of landscape metrics. Because of its form, a grid-based diversity map could be thought of as a diversity "landscape" and analyzed quantitatively using landscape metrics. We give a brief summary of most pertinent metrics and demonstrate how they can be applied to diversity maps.


Fluid resuscitation in pre-hospital trauma care: a consensus view.
Fluid administration for trauma in the pre-hospital environment is a challenging and controversial area. The available evidence does not clearly support any single approach. Nevertheless, some provisional conclusions may be drawn. It was with this intention that the Faculty of Pre-Hospital Care (RCSEd) arranged to meet in August 2000 in an attempt to reach a working consensus. The following guidelines are the result of those discussions. It is intended that they will be modified as future research brings clarity to the area. When treating trauma victims in the pre-hospital arena cannulation should take place en route, where possible. Only two attempts at cannulation should be made. Transfer should not be delayed by attempts to obtain intravenous access. Entrapped patients require cannulation at the scene. Normal saline may be titrated in boluses of 250 ml against the presence or absence of a radial pulse (caveats; penetrating torso injury, head injury, infants).


The Assessment of the Diagnostic Delay in Japanese People with Parkinson's Disease Using a Web-based Survey of Patients and Physicians.
Objective Although diagnostic criteria of Parkinson's disease (PD) have been established, the details of the process by which patients notice symptoms, visit a physician, and receive a diagnosis of PD is unclear. We therefore explored factors influencing latency in diagnosing PD. Methods We performed an internet-based survey of patients with PD and their families as well as physicians treating patients with PD to identify any diagnostic latency and its determinants. Evaluated factors included motor and non-motor symptoms, the diagnosis history and symptoms, patients' feelings toward PD prior to the diagnosis, and physician-determined reasons for the diagnostic delay. Results Among the 186 eligible patient respondents (including 87 responses from family members of patients), 24% received a PD diagnosis >1 year after the onset of PD-related symptoms, 58.6% had mid- or late-stage PD at the diagnosis, and 29% of patients had initially thought their symptoms were common age-related phenomena. Tremor (42%) was the most frequent symptom that led patients to visit a medical institution, whereas gait disturbance (14%) was the least frequent. More patients diagnosed with early-stage PD than those diagnosed with mid- or late-stage PD consulted a neurologist at their first visit. Among the 331 eligible physicians, patients' misinterpretation of their symptoms as being age-related was deemed one of or the most common cause (s) of a diagnostic delay by 67% and 36%, respectively. Conclusion Patients' insufficient or misinterpreted information about PD may cause delays in accessing healthcare services, leading to diagnostic delay.


Visual disorders or "eye stroke"after heart surgery: can we prevent it?
The aim of the study was to elucidate the problem of visual disorders after heart surgery, focusing on aetiology, modes of prevention and treatment. Information from a literature search and the authors' personal experience are provide clues as to the modes of development and the means of avoidance and therapy of this category of postoperative, neurosensory complications. Multiple morbid situations, such as preoperative augmented ocular pressure, perioperative bleeding and hypotension, are shown to be predisposing and precipitating factors. Medical treatment seems to be less important than minimisation of risk factors. Prevention rather than treatment is more helpful for heart-operated patients, as far as postoperative visual disorders are concerned.


[New technique for intestinal lengthening -- from the idea to the clinical application].
In severe short bowel syndrome, as a result of the natural adaptation, the bowel becomes overdilated, this interferes with the persitalsis and may lead to stasis, bacterial translocation and sepsis. At present two techniques are used to improve peristalsis. The Bianchi procedure is technically challenging, the Serial Transverse Enteroplasty (STEP) is easy however it results in an aphysiological ultrastructure altering the orientation of the muscle fibres. Our aim was to develop an easy technique, which does not alter intestinal muscular ultrastructure dramatically. The idea, Spiral Intestinal Lengthening and Tailoring (SILT), is based on a spiral shape incision of the intestine and retubularisation in a longer but narrower fashion. The feasibility and the effect on the muscular ultrastructure were tested on bowelsimulator and porcine intestine. The intramural microcirculation was checked with intravital microscopy. The outcome was assessed on minipigs (n = 6) than clinical application was commenced. SILT was feasible, did not change the orientation of muscle fibres significantly, did not compromised microcirculation, no surgical complication was noted when tailoring did not exceed 75%. The first clinical application was successful. SILT is a safe and easy technique and not altering the intestinal musculature significantly.