Treatment of myocardial infarction in the United States (1990 to 1993). Observations from the National Registry of Myocardial Infarction.
Multiple clinical trials have provided guidelines for the treatment of myocardial infarction, but there is little documentation as to how consistently their recommendations are being implemented in clinical practice. Demographic, procedural, and outcome data from patients with acute myocardial infarction were collected at 1073 US hospitals collaborating in the National Registry of Myocardial Infarction during 1990 through 1993. Registry hospitals composed 14.4% of all US hospitals and were more likely to have a coronary care unit and invasive cardiac facilities than nonregistry US hospitals. Among 240,989 patients with myocardial infarction enrolled, 84,477 (35.1%) received thrombolytic therapy. Thrombolytic recipients were younger, more likely to be male, presented sooner after onset of symptoms, and were more likely to have localizing ECG changes. Among the 60,430 patients treated with recombinant tissue-type plasminogen activator (rTPA), 23.2% received it in the coronary care unit rather than in the emergency department. Elapsed time from hospital presentation to starting rTPA averaged 99 minutes (median, 57 minutes). Among patients receiving thrombolytic therapy, concomitant pharmacotherapy included intravenous heparin (96.9%), aspirin (84.0%), intravenous nitroglycerin (76.0%), oral beta-blockers (36.3%), calcium channel blockers (29.5%), and intravenous beta-blockers (17.4%). Invasive procedures in thrombolytic recipients included coronary arteriography (70.7%), angioplasty (30.3%), and bypass surgery (13.3%). Trend analyses from 1990 to 1993 suggest that the time from hospital evaluation to initiating thrombolytic therapy is shortening, usage of aspirin and beta-blockers is increasing, and usage of calcium channel blockers is decreasing. This large registry experience suggests that management of myocardial infarction in the United States does not yet conform to many of the recent clinical trial recommendations. Thrombolytic therapy is underused, particularly in the elderly and late presenters. Although emerging trends toward more appropriate treatment are evident, hospital delay time in initiating thrombolytic therapy remains long, aspirin and beta-blockers appear to be underused, and calcium channel blockers and invasive procedures appear to be overused.


Multimode waveguide crossing based on a square Maxwell's fisheye lens.
Mode-division multiplexing (MDM) is an emerging large-capacity data communication technology utilizing orthogonal guiding modes as independent data streams. One of the challenges of multimode waveguide routing in MDM systems is decreasing the mode leakage of waveguide crossings. In this article, a square Maxwell's fish-eye lens as a waveguide crossing medium based on quasiconformal transformation optics is designed and implemented on a silicon-on-insulator platform. Two approaches were taken to realize the designed lens: graded photonic crystal and varying the thickness of the silicon slab waveguide. Three-dimensional numerical simulations show that the designed multimode waveguide crossing has an ultrawide bandwidth from 1260 to 1675 nm with a compact footprint of only 3.77×3.77 μm2. For the first three transverse electric modes (TE0, TE1, and TE2), the designed waveguide crossing exhibits an average insertion loss of 0.24, 0.55, and 0.45 dB; a crosstalk of less than -72, -61, and -27 dB; and a maximum return loss of 54, 53, and 30 dB, respectively. The designed waveguide crossing supports low-distortion pulse transmission with a high fidelity factor of 0.9857. Furthermore, the proposed method can be expanded to design waveguide crossings with an even higher number of supporting modes by increasing the size of the lens.


Involvement of Sub-Bandgap States in Subpicosecond Exciton and Biexciton Dynamics of Ternary AgInS2 Nanocrystals.
We have synthesized three AgxInS2 (AIS) ternary nanocrystals (NCs), where x varies from 0.25 to 1, and reported their biexcitonic feature which depends on the stoichiometry ratio of Ag/In. The broadening of absorption band and dual photoluminescence in different AIS NCs indicates the existence of Ag-related sub-bandgap (S-states) and antisite states. Ultrafast charge carrier dynamics in AIS NCs that involve multiple states like higher excited state, band-edge, Ag-related sub-bandgap, and antisite states have been carried out by employing femtosecond transient absorption spectroscopy, which strongly depends on Ag/In ratio. The probe-induced biexcitonic feature that originated from antisite state has been observed in these AIS NCs even at low pump fluency (<N> = ∼0.2). The enhancement of binding energy of biexciton and slow down of electron cooling dynamics has been demonstrated by gradual increment of pump fluence as well as with different stoichiometry of Ag and In.


Liquid imidazole-borane complex.
Physical properties of liquid imidazole-borane complex were investigated to demonstrate their utility as aprotic polar solvents or liquid electrolytes appropriate for selective ion transport.


Enantioselective Synthesis of Pyrrolopyrimidine Scaffolds through Cation-Directed Nucleophilic Aromatic Substitution.
The catalytic enantioselective synthesis of 3-aryl-substituted pyrrolopyrimidines (PPYs), a common motif in drug discovery, is achieved through a kinetic resolution via quaternary ammonium salt-catalyzed nucleophilic aromatic substitution (SNAr). Both enantioenriched products and starting materials can be functionalized with no observed racemization to give enantiodivergent access to diverse chiral analogues of an important class of kinase inhibitor. One of the compounds was found to be a potent and selective inhibitor of breast tumor kinase.


DNA double strand break (DSB) induction and cell survival in iodine-enhanced computed tomography (CT).
A multi-scale Monte Carlo model is proposed to assess the dosimetric and biological impact of iodine-based contrast agents commonly used in computed tomography. As presented, the model integrates the general purpose MCNP6 code system for larger-scale radiation transport and dose assessment with the Monte Carlo damage simulation to determine the sub-cellular characteristics and spatial distribution of initial DNA damage. The repair-misrepair-fixation model is then used to relate DNA double strand break (DSB) induction to reproductive cell death. Comparisons of measured and modeled changes in reproductive cell survival for ultrasoft characteristic k-shell x-rays (0.25-4.55 keV) up to orthovoltage (200-500 kVp) x-rays indicate that the relative biological effectiveness (RBE) for DSB induction is within a few percent of the RBE for cell survival. Because of the very short range of secondary electrons produced by low energy x-ray interactions with contrast agents, the concentration and subcellular distribution of iodine within and near cellular targets have a significant impact on the estimated absorbed dose and number of DSB produced in the cell nucleus. For some plausible models of the cell-level distribution of contrast agent, the model predicts an increase in RBE-weighted dose (RWD) for the endpoint of DSB induction of 1.22-1.40 for a 5-10 mg ml-1 iodine concentration in blood compared to an RWD increase of 1.07 ± 0.19 from a recent clinical trial. The modeled RWD of 2.58 ± 0.03 is also in good agreement with the measured RWD of 2.3 ± 0.5 for an iodine concentration of 50 mg ml-1 relative to no iodine. The good agreement between modeled and measured DSB and cell survival estimates provides some confidence that the presented model can be used to accurately assess biological dose for other concentrations of the same or different contrast agents.


Novel Dimethylacetamide-Containing Formulation Improves Infraorbital Anaesthesia Efficacy in Rats with Periodontitis.
To evaluate acute toxicity and local anaesthetic activity of a formulation containing a novel dimethylacetamide derivative, antioxidant, and vasoconstrictor in rats with chronic periodontitis. Novel anaesthetic dimethylacetamide-containing formulation LHT-15-32 was studied as 2% water solution. Its acute intravenous and subcutaneous toxicity was determined in mice. Pain sensitivity threshold of the upper second molar was determined in rats with experimental periodontitis. Oxidative stress activity and total antioxidant capacity were determined in rats' gingival mucosa by induced chemiluminescence. Local changes were evaluated in periodontal tissue by morphological examination. Tissue IL-1β, IL-10, and TNF-α concentration was quantitatively assessed by an enzyme-linked immunosorbent assay. LHT-15-31 Na-blocking activity was studied on isolated neurons of Limnaea stagnalis' parapharyngeal ganglion. Isolated sciatic nerve of Rana radibunda was perfused with different concentrations of LHT-15-32 to assess its conductivity. Statistical analysis was used, and continuous variables were presented as mean ± square deviation. The normality of distribution was determined using ANOVA. Newman-Keuls parametric criterion was used for intergroup comparison. LD50 indexes were calculated by probit analysis. LHT-15-32 acute intravenous and subcutaneous toxicity was lower than that of its active substance. The formulation by infraorbital administration induced deep dental anaesthesia which lasted over 70 min and activated the local antioxidant defense system and decreased IL-1β level in gingival tissue. LHT-15-32 triggered tissue reparation around the impacted upper molar in rats assessed five days after administration. At 10-6 to 10-3 M concentration, LHT-15-32 inhibited sciatic nerve conductivity and blocked Na+ channels of isolated neurons in a dose-dependent manner. The formulation may be considered as an effective and safe approach to anaesthetize upper molars with periodontitis.


Aerosol gene delivery using viral vectors and cationic carriers for in vivo lung cancer therapy.
Lung cancer has the highest mortality rate among all cancers in both men and women. Aerosol delivery is a noninvasive method for gene delivery to the lungs, although efficient and biocompatible vectors need to be developed for lung cancer therapy. This review summarizes recent advances in airway gene delivery for lung cancer treatment in animal models using viral vectors or cationic polymers. Viral vectors including lentiviruses and adenoviruses have been used for airway gene delivery because of their high transfection efficiency. Cationic polymers have also been developed for aerosol gene therapy owing to their biocompatibility and ease of modification. Efficient delivery and specific promoters are needed for lung cancer therapy. Capsid engineering or PEGylation can lower immunogenicity. Moreover, immunotherapy and oncolytic viruses need to be tested with aerosol delivery for lung cancer therapy. Meanwhile, naturally existing cationic materials may allow the development of novel and biocompatible carriers. In combination with various technologies for aerosol delivery, novel and specific carriers could be developed for lung cancer therapy in the future. Finally, standardized protocols for quantifying and manufacturing viral vectors and cationic polymers need to be developed in order to ensure biosafety.


Rectal cancer: incidence of pulmonary metastases on thoracic CT and correlation with T staging.
The aim of the study was to evaluate the incidence of pulmonary metastases detected on thoracic computed tomography in patients with rectal cancer and assess the association between the incidence of pulmonary metastases and the stage of the rectal tumor. Fifty-six consecutive patients who were diagnosed with rectal cancer over a 22-month period were included in the study. These patients had local tumor staging with a pelvic magnetic resonance imaging and staging computed tomographic scan of the chest and upper abdomen immediately after the magnetic resonance imaging. Two radiologists retrospectively reviewed all the thoracic imaging performed on these patients for the presence of metastases. The presence of a parenchymal lung nodule (greater than or equal to 1 cm if single and 0.5 cm if multiple) with a soft tissue component without calcification on lung and mediastinal window settings was considered positive for the presence of metastasis. All other patients were considered as not having any lung metastases. Of the 56 patients, 10 (17.9%) had evidence of pulmonary metastases on computed tomography. Of the 56 patients, there were 3 patients with stage T1, 24 with T2, 26 with T3, and 3 with stage T4 tumors. Of these 10 patients, 1 had a stage T2 tumor, 7 had T3, and 2 had stage T4 tumors. Statistical analysis using exact logistic regression showed the odds of getting lung metastases is an increasing function of tumor grade. There is a high incidence of lung metastases in patients with rectal cancer, and thoracic computed tomographic scanning should be performed as part of a staging protocol in all patients before any form of treatment is planned. There is a higher incidence of lung metastases with higher T stage.


Functions and regulation of the MRX complex at DNA double-strand breaks.
DNA double-strand breaks (DSBs) pose a serious threat to genome stability and cell survival. Cells possess mechanisms that recognize DSBs and promote their repair through either homologous recombination (HR) or non-homologous end joining (NHEJ). The evolutionarily conserved Mre11-Rad50-Xrs2 (MRX) complex plays a central role in the cellular response to DSBs, as it is implicated in controlling end resection and in maintaining the DSB ends tethered to each other. Furthermore, it is responsible for DSB signaling by activating the checkpoint kinase Tel1 that, in turn, supports MRX function in a positive feedback loop. The present review focuses mainly on recent works in the budding yeast Saccharomyces cerevisiae to highlight structure and regulation of MRX as well as its interplays with Tel1.


Modification of an ecotoxicological rating to bioassess small acid mine drainage-impacted watersheds exclusive of benthic macroinvertebrate analysis.
The modified ecotoxicological rating (METR) approach to synthesizing integrative bioassessment data into a single number ranging from 0 to 100 was found to differentiate between multiple levels of impacts from acid mine drainage (AMD). Our objective was to develop a more cost-effective and time-efficient bioassessment technique than previously used in other large scale ecotoxicological ratings (ETRs) by minimizing the number of parameters required to rank stations to only those most descriptive of the benthic macroinvertebrate community responses to AMD. Nineteen physical, chemical, toxicological, and ecological measurements were made at 38 stations in two adjacent watersheds. The most descriptive parameters were selected through multiple linear regression analysis, bivariate correlation analysis, and one-way analysis of variance. We found that habitat assessment, 30-d in situ Asian clam survival, mean conductivity, and mean total water column concentration of aluminum and manganese were the most descriptive parameters. The METR constructed from these parameters was equally effective at differentiating stations as were two previous published ETRs that incorporated up to 10 parameters, including benthic macroinvertebrate indices. When the METR was applied to a new watershed, the scores were significantly correlated with benthic macroinvertebrate indices for those stations.


Immunohistopathology of papillary cystadenoma lymphomatosum (Warthin's tumor).
A retrospective study of various benign salivary gland neoplasms was designed to study the frequency distribution and density of immunoglobulins (Igs) located within their various tissue compartments. Buffered-formalin fixed, paraffin embedded sections of Warthin's tumor, cystadenoma, oncocytoma, autoimmune thyroiditis, normal salivary gland, and reactive peripheral lymph node were obtained and processed via the peroxidase-antiperoxidase method following trypsinization to re-expose antigenic sites. The subepithelial and parafollicular zones of Warthin's tumor show an Ig density distribution (IgA greater than or equal to IgG) much greater than IgM, but the relative densities in the germinal center are (IgG = IgM) much greater than IgA. In contrast, the normal salivary gland displays almost exclusively IgA positive cells with only an occasional IgG or IgM positive cell. In general, the three salivary gland neoplasms considered all display a relatively similar frequency distribution with (IgA greater than or equal to IgG) much greater than IgM and much greater densities of all Igs than encountered in the normal salivary gland; however, the densities of IgA and IgG positive cells are greatest in Warthin's tumor. A similar frequency distribution of immunocytes in the parafollicular zone of autoimmune thyroiditis and Warthin's tumor is noted with an increased density of all Igs occurring in autoimmune thyroiditis. A significant increase in the density of IgA immunocytes is noted in the germinal centers of autoimmune thyroiditis. A comparison of Warthin's tumor with a reactive peripheral lymph node shows a marked increase in the density and frequency of IgA in the parafollicular zone in the former lesion, and significant elevations of IgG and IgM in the latter process both in the parafollicular zone and in the germinal centers. No data generated by this study support an autoimmune etiology of Warthin's tumor. Histopathologically, the oncocytoma appears to represent a pathologic entity distinctly different from papillary cystadenoma lymphomatosum. Our data tend to support the hypothesis that Warthin's tumor arises within ectopic salivary gland elements trapped within paraparotid or intraparotid lymph nodes during embryogenesis. The cystadenoma appears to represent a similar pathologic process arising in salivary gland elements independent of lymphoid tissue.


Efficacy and safety of low dose aspirin plus clopidogrel in the treatment of elderly patients with symptomatic intracranial artery stenosis.
As one of the most common causes of stroke, symptomatic intracranial artery stenosis (sICAS) is a great threat to public health, and its financial burden is substantial, with annual direct high medical costs particularly in China. Currently, the long-term use of conventional dual antiplatelet therapy (DAPT) as the primary modality of treatment for sICAS decreases the risk of stroke recurrence but increases the risk of bleeding. We aimed to evaluate the efficacy and safety of low dose aspirin plus clopidogrel for the treatment of sICAS in the elderly population. This randomized, controlled study included 181 older patients with transient ischemic attack (TIA) or ischemic stroke (IS) attributed to sICAS, who were recruited between April 2015 and November 2020. The 90 patients assigned to the low dose therapy group included aspirin, 75 mg, plus clopidogrel, 50 mg, daily for 90 and 91 patients assigned to the conventional group included aspirin, 100 mg, plus clopidogrel, 75 mg, daily for 90 days (aspirin or clopidogrel alone daily thereafter) were included in this intention-to-treat analysis. Efficacy and safety analyses were done in this trial. One hundred eighty-one eligible elderly patients with sICAS were enrolled in this trial. The median age was 70 years ranged 60-83 years. Seventy-five participants were with TIA and 106 with IS. The median time of follow-up was 30 months ranged 1-36 months. Ninety patients were assigned randomly to the low dose group and 91 patients to the conventional group. The rate of primary, secondary and composite efficacy were not significantly different between the low dose and conventional group (P > 0.05). The rate of composite safety outcome was 7.8% (7/90) in the low dose group, which was lower than 17.6% (16/91) in the conventional group (χ2 = 3.921, P = 0.048). At the time of last follow-up, 17 (9.4%) of 181 patients developed GI injuries, which occurred in four (4.4%) of 90 patients in the low dose group and in 13 (14.3%) of 91 patients in the conventional group (χ2 = 4.058, P = 0.044). The primary efficacy outcome occurred in six (18.2%) of 33 patients with severe sICAS and in 22 (38.6%) of 57 patients with moderate sICAS (χ2 = 4.064, P = 0.044) in the low dose group. In this study, the safety of low dose aspirin combined with clopidogrel proved to be equally efficient and significantly safer than those of conventional dose within 24 months in elderly patients with sICAS. However, the small size of this study limits the validity of the results. Further larger longitudinal and randomized controlled trials are necessary to evaluate the role of low dose DAPT in the patients with sICAS.


Phase I trial design for solid tumor studies of targeted, non-cytotoxic agents: theory and practice.
New targeted, non-cytotoxic anticancer agents, such as small-molecule kinase inhibitors, pose challenges to the current phase I paradigm of dose selection based on toxicity. Moreover, increasing the drug dose to toxicity may be unnecessary for drug effect, making the use of maximum tolerated dose as a surrogate of effective dose inappropriate in the phase I setting. Because little is known about the optimal methods of recommended phase II dose selection of targeted, non-cytotoxic therapies, we reviewed the strategies that were used in completed phase I studies of these drugs. We retrieved 60 publications of phase I studies involving 31 single agents representative of the most common targets of interest in the oncology literature. For each publication, we abstracted data regarding patient population, starting dose, methods of dose escalation and determination of recommended phase II dose, and inclusion of correlative studies in study conduct. Of the 60 completed phase I studies, 36 used toxicity and eight used pharmacokinetic data as endpoints for selection of the recommended phase II dose. Nontraditional endpoints, such as measures of molecular drug effects in tumor or surrogate tissue or functional imaging studies, were not routinely incorporated into the study design and rarely formed the primary basis for dose selection. To date, phase I studies of targeted anticancer agents have generally used traditional endpoints for selection of the recommended phase II dose. More research is needed to define suitable molecular measures of drug effect and the means to incorporate them in the early drug development process.


Bacterial Contamination on Latrine Surfaces in Community and Household Latrines in Kathmandu, Nepal.
A lack of sanitation infrastructure is a major contributor to the global burden of diarrheal disease, particularly in low-income countries. Access to basic sanitation was identified as part of the 2015 United Nations Sustainable Development Goals. However, current definitions of "basic" sanitation infrastructure exclude community or shared sanitation, due to concerns around safety, equity, and cleanliness. The purpose of this study was to measure and compare bacterial contamination on community and household latrine surfaces in Kathmandu, Nepal. One hundred and nineteen swab samples were collected from two community and five household latrines sites. Community latrine samples were taken before and after daily cleaning, while household samples were collected at midday, to reflect normal conditions. Concentrations of total coliforms and Escherichia coli were measured using membrane filtration methods. Results found almost no differences between bacterial contamination on latrine surfaces in community and household latrines, with the exception of latrine slabs/seats that were more contaminated in the community latrines under dirty conditions. The study also identified surfaces with higher levels of contamination. Findings demonstrated that well-maintained community latrines may be as clean, or cleaner, than household latrines and support the use of community latrines for improving access to sanitation infrastructure in a low-income country setting.


Histopathologic evaluation of the internal limiting membrane surgically excised from eyes with diabetic maculopathy.
To histopathologically evaluate the internal limiting membrane (ILM) in diabetic eyes with macular edema as compared to nondiabetic controls. The authors ultrastructurally and immunohistochemically studied ILM specimens that were intentionally peeled from five eyes with diabetic maculopathy, comprising four with diffuse diabetic macular edema and one with macular hole accompanying diabetic retinopathy (DM group), and five with nondiabetic idiopathic macular hole (MH group). They compared ultrastructural and immunohistochemical findings between the two groups. A larger amount of cellular elements was observed on the vitreous side of the ILM in the DM group. The thickness of the ILM in the DM group was significantly increased (mean 4.8 +/- 1.6 microm) compared with that in the MH group (1.8 +/- 0.6 microm) (P < 0.0001). Immunoreactions for heparan sulfate proteoglycan in the ILM were more abundant in the DM group than in the MH group. The ILM thickening and cell abundance on the vitreous surface might contribute to the course and the pathogenesis of diabetic maculopathy.


Developments in radiation sterilisation.
This article outlines significant recent developments in radiation sterilisation and some of the initiatives currently underway. These include work on a method for sterilising combination products and revisions to several sterilisation guidelines, including those for selecting appropriate sterility assurance levels.


Indicators for nursing practice: the use of research findings.
Until recently discussion about nursing research centred on the need to get it carried out. Attention is now being focused on how to get nursing research used, since so far, such research findings has not, on the whole, been assimilated into practice. Until this occurs the practice of nursing will not and cannot be research-based in any meaningful way. It is postulated that nursing research findings provide nurses with indicators for practice. This assumes that such findings are available and that the main barrier to their use is the poor communication of this research, (in a form they can understand) to nurse practitioners. However recent research into the use of research findings casts doubt on this assumption and it can be argued that such a view is too simplistic. In this paper therefore, three questions are asked: (1) Are relevant nursing research findings available which provide indicators for practice? (2) What indicators do such findings provide? (3) Are such findings used by nurse-practitioners? Using specific examples from nursing research, ideas and suggestions are put forward which provide a basis for possible answers. Finally the paper discusses the interdependence of research and practice and the need for them to develop together.


Two-dimensional Ising model on random lattices with constant coordination number.
We study the two-dimensional Ising model on networks with quenched topological (connectivity) disorder. In particular, we construct random lattices of constant coordination number and perform large-scale Monte Carlo simulations in order to obtain critical exponents using finite-size scaling relations. We find disorder-dependent effective critical exponents, similar to diluted models, showing thus no clear universal behavior. Considering the very recent results for the two-dimensional Ising model on proximity graphs and the coordination number correlation analysis suggested by Barghathi and Vojta [Phys. Rev. Lett. 113, 120602 (2014)PRLTAO0031-900710.1103/PhysRevLett.113.120602], our results indicate that the planarity and connectedness of the lattice play an important role on deciding whether the phase transition is stable against quenched topological disorder.


Proton Intercalation/De-intercalation Chemistry in Phenazine-based Anode for Hydronium-ion Batteries.
Hydronium-ion batteries have received significant attention owing to the merits of extraordinary sustainability and excellent rate abilities. However, achieving high-performance hydronium-ion batteries remains a challenge due to the inferior properties of anode materials in strong acid electrolyte. Herein, a hydronium-ion battery is constructed which is based on a diquinoxalino [2,3-a:2',3'-c] phenazine (HATN) anode and a MnO2 @graphite felt cathode in a hybrid acidic electrolyte. The fast kinetics of hydronium-ion insertion/extraction into HATN electrode endows the HATN//MnO2 @GF battery with enhanced electrochemical performance. This battery exhibits an excellent rate performance (266 mAh g-1 at 0.5 A g-1 , 97 mAh g-1 at 50 A g-1 ), attractive energy density (182.1 Wh kg-1 ) and power density (31.2 kW kg-1 ), along with long-term cycle stability. These results shed light on the development of advanced hydronium-ion batteries.


Spatial distribution of the human development index, HIV infection and AIDS-Tuberculosis comorbidity: Brazil, 1982-2007.
AIDS epidemic has given visibility to the incidence of tuberculosis, for being the most frequent opportunistic infection. It is known that individuals who are socially vulnerable are more susceptible to HIV transmission and tuberculosis as well. This study aims to conduct a geoepidemiological study on HIV/AIDS, AIDS-Tuberculosis co-infection and social vulnerability. This is an ecological study using incidence rates and the human development index to produce thematic maps and a descriptive analysis of epidemiology. The records of reported cases of HIV/AIDS from 1982 to 2007 were used, considering as cases of AIDS-Tuberculosis those records that were positively diagnosed with tuberculosis and those records with unknown diagnosis of tuberculosis, but showing compatible signs and symptoms with tuberculosis (fever, cough, cachexia and asthenia). The maps allowed the identification of areas with social differences and different patterns of incidence of HIV/AIDS and AIDS-Tuberculosis; regional differences were similar to those found by Josué de Castro, in 1940; regions with higher human development index values also showed higher incidence HIV/AIDS and AIDS-Tuberculosis. The prevention of HIV infection must be geographically specific, given socioeconomic and cultural differences. Although official records show decline in AIDS-TB co-infection, treatment of cases of HIV/AIDS should observe the occurrence of opportunistic diseases, which should be notified and/or updated.


Characterization of the cDNA and amino acid sequences of Xenopus Metaxin 3, and relationship to Xenopus Metaxins 1 and 2.
The cDNA and protein structures of Xenopus metaxin 3, along with those of Xenopus metaxins 1 and 2, have been characterized. A protein of 309 amino acid residues is encoded by X. laevis metaxin 3 (XMTX3) cDNA. In comparison, the cDNA of X. laevis metaxin 1 (XMTX1) specifies a protein of 320 residues, while the metaxin 2 cDNAs of X. laevis (XMTX2) and X. tropicalis (SMTX2) both specify proteins of 274 amino acids. Aligning the amino acid sequences of XMTX3 and XMTX1 showed 39% identities; 22% identities were found for XMTX3 and XMTX2. However, 55% amino acid identities were revealed in aligning the XMTX3 and zebrafish metaxin 3 sequences. The construction of a phylogenetic tree gave further evidence for the existence of three distinct groups of metaxin genes and their common ancestry. Two conserved protein domains are present in each of the Xenopus metaxins: a glutathione S-transferase (GST) domain and a thioredoxin-like domain. The protein secondary structure predicted for the Xenopus metaxins is dominated by regions of alpha helix which alternate with regions that are neither alpha helix nor beta strand.


SAR131675 Receptor Tyrosine Kinase Inhibitor Induces Apoptosis through Bcl- 2/Bax/Cyto c Mitochondrial Pathway in Human Umbilical Vein Endothelial Cells.
Tyrosine Kinase Inhibitors (TKIs) can be used to inhibit cancer cell proliferation by targeting the vascular endothelial growth factor receptor (VEGFR) family. SAR131675 is a highly selective receptor tyrosine kinase inhibitor to VEGFR3 that reveals the inhibitory effect on proliferation in human lymphatic endothelial cells. However, the molecular mechanisms underlying this process are generally unclear. This study was performed to investigate the possible involvement of the Bcl-2/Bax/Cyto c apoptosis pathway in Human Umbilical Vein Endothelial Cells (HUVECs). In addition, the role of Reactive Oxygen Species (ROS) and mitochondrial membrane potential was evaluated. The effect of SAR131675 on HUVEC cell viability was evaluated by MTT assay. The activity of SAR131675 in inducing apoptosis was carried out through the detection of Annexin V-FITC/PI signal by flow cytometry. To determine the mechanisms underlying SAR131675 induced apoptosis, the mitochondrial membrane potential, ROS generation, the activity of caspase-3, and expression of apoptosis-related proteins such as Bcl-2, Bax, and cytochrome c were evaluated in HUVECs. SAR131675 significantly inhibited cell viability and induced apoptosis in HUVECs in a dose-dependent manner. Moreover, SAR131675 induced mitochondrial dysfunction, ROS generation, Bcl-2 down-regulation, Bax upregulation, cytochrome c release, and caspase-3 activation, which displays features of mitochondria-dependent apoptosis signaling pathway. Our present data demonstrated that SAR131675-induced cytotoxicity in HUVECs associated with the mitochondria apoptotic pathway. These results suggest that further studies are required to fully elucidate the role of TKIs in these cellular processes.


Monitoring of the comatose patient.
Monitoring of comatose patients involves a close followup of clinical findings and a number of various techniques. These techniques may be differentiated in invasive and non invasive techniques. The benefit of these techniques is controversial as to their effect on the actual therapy of the comatose patient. The benefit of sedation beyond the point of what is required for adequate sedation is questioned, as it makes clinical observation useless. Since there is no evidence that any technical monitoring is as sensitive and reliable as clinical monitoring, the reliance on only technical monitoring needs to be discussed.


The multiple meanings of masochism in psychoanalytic discourse.
The term masochism was originally used in a narrow, specifically sexual sense (referring to perversions ), but has come to encompass for many analysts an exceedingly broad and variably determined range of clinical phenomena that bear no consistent relation to sexual excitement. In addition, these expanding clinical perspectives have long been entangled with Freud's shifting metapsychological constructions designed to ground masochism in instinctual theory. As a result, the term is used with little consistency and at varied levels of abstraction: loosely descriptive, dynamic, theoretical. It is not always explicit which meaning is intended or what inferences, if any, are meant to be drawn from the term. When used in its broadest sense, masochism may falsely suggest dynamic similarity between diverse phenomena, and is often ambiguous with respect to the presence or absence of underlying erotic or perverse excitement. In the clinical situation, the categorization of material as masochistic may evoke an associated set of genetic, dynamic, or theoretical ideas which may alter the perception, ordering, and interpretation of clinical data. Particularly conducive to this subtle steering process are the enduring influence of the early concept of feminine masochism and the related concept of sadistic and masochistic paired opposite component sexual instincts--a theoretical, physicalistic , linear concept incompatible with the clinical model of overdetermination and multiple function. This paper includes a review of the terminological and conceptual history of masochism, briefly touches on the parallel history of sadism , and offers some provisional definitional solutions.


Histoplasma capsulatum yeast phase-specific protein Yps3p induces Toll-like receptor 2 signaling.
Histoplasma capsulatum is a common cause of fungal infection in certain geographic areas, and although most infections are asymptomatic, it is capable of causing histoplasmosis, a disseminated, life-threatening disease, especially in immunocompromised individuals. A deeper understanding of this host-pathogen interaction is needed to develop novel therapeutic strategies to counter lethal infection. Although several lines of evidence suggest that this fungus is neurotropic in HIV patients, little is known about the immunobiology of Histoplasma infection in the central nervous system [CNS]. The goal of the present study was to understand the innate neuroimmune mechanisms that recognize H. capsulatum during the initial stages of infection. Using a 293T stable cell line expressing murine Toll-like receptor 2 [TLR2], we show here that TLR2 recognizes H. capsulatum cell wall protein Yps3p and induces the activation of NF-kappaB. In further experiments, we tested the ability of Yps3p to induce signaling from TLR2 in primary microglial cells, the resident brain macrophages of the CNS. Our data show that H. capsulatum Yps3p induced TLR2 signaling in wild-type microglia, but not in microglia isolated from TLR2 KO mice, confirming that Yps3p is a ligand for TLR2. Furthermore, Yps3p-induced TLR2 signaling was suppressed by vaccinia virus-encoded TLR inhibitors. This is the first demonstration of a fungal protein serving as a TLR ligand and mediating signaling in primary brain cells.


Adverse effects of antituberculosis drugs causing changes in treatment.
The adverse effects of drugs which caused changes in therapeutic regimens have been studied in 511 patients with pulmonary tuberculosis, at the Pavilion Koch of Buenos Aires University. In 384 patients who had not received any treatment before, the frequency of such modifications was 6.5%, and in 127 retreated patients it was 15.0%. The characteristics of the adverse effects and the measures aimed at reducing them were studied.


Three-Electron Transfer-Based High-Capacity Organic Lithium-Iodine (Chlorine) Batteries.
Conversion-type batteries apply the principle that more charge transfer is preferable. The underutilized electron transfer mode within two undermines the electrochemical performance of halogen batteries. Here, we realised a three-electron transfer lithium-halogen battery based on I- /I+ and Cl- /Cl0 couples by using a common commercial electrolyte saturated with Cl- anions. The resulting Li||tetrabutylammonium triiodide (TBAI3 ) cell exhibits three distinct discharging plateaus at 2.97, 3.40, and 3.85 V. Moreover, it has a high capacity of 631 mAh g-1 I (265 mAh g-1 electrode , based on entire mass loading) and record-high energy density of up to 2013 Wh kg-1 I (845 Wh kg-1 electrode ). To support these findings, experimental characterisations and density functional theory calculations were conducted to elucidate the redox chemistry involved in this novel interhalogen strategy. We believe our paradigm presented here has a foreseeable inspiring effect on other halogen batteries for high-energy-density pursuit.


Comparison of motion restriction and trunk stiffness provided by three thoracolumbosacral orthoses (TLSOs).
The amounts of thoracic and lumbar spine motion restriction and passive trunk stiffness provided by three thoracolumbosacral orthoses (TLSOs) (Aspen TLSO, Boston Body Jacket, and CAMP TLSO) were compared. Ten subjects executed maximum trunk flexion, extension, and lateral bending motions. The spine motion was measured noninvasively with a thin strain gauge device (Flexducer), and passive trunk stiffness around the neutral posture was estimated from an electromyography-assisted biomechanical model. No significant differences in either the restriction of motion or the amount of added passive trunk stiffness were found between the three orthoses. The subjects also did not perceive any difference in the restriction of motion but rated the Aspen TLSO significantly more comfortable than the other two orthoses. The rigid custom orthosis design may not be important for restricting the spine motion and providing passive trunk stiffness, or there may be other measures that reflect better the function of orthoses.


Systematic reviews of pharmacy practice research: methodologic issues in searching, evaluating, interpreting, and disseminating results.
Although there has been a large number of trials on pharmacist care, often demonstrating clinically significant benefits, the trials generally have not changed practice or healthcare policy. What is needed are focused evidence syntheses, such as a systematic review. A systematic review is defined as a summary that addresses a focused clinical question, using methods to reduce the likelihood of bias. These reviews, which are the highest level of evidence, can help to impact policy by bringing together results of various trials. However, systematic reviews of practice research pose some unique methodologic challenges, including issues with searching, interpreting, and evaluating the available research. Well-conducted systematic reviews of pharmacist interventions could go a long way toward changing pharmacy practice and healthcare policy to recognize the important impact that pharmacists could have in the healthcare system.


Surveillance of postoperative infections in thoracic surgery.
Postoperative infections (PIs) are serious complications of thoracic surgery. To gain insight into the nature and the scope of the problem, an 18-month prospective surveillance was conducted at the department of thoracic surgery of the University Hospital Rotterdam, Dijkzigt. PI were classified according to CDC criteria. One hundred and ninety-four out of 983 patients (19.7%) developed one or more PIs and in these 194 patients, 268 PIs were diagnosed. The incidence of PI was 2.0 per 100 days of postoperative stay. The mean postoperative length of stay (LOS) of the 194 patients with PI was 14.1 days longer than those without PI. Deep surgical wound infections (DSWIs) were associated with the longest prolongation of the median postoperative LOS in the hospital (30 days longer). Although lower than DSWIs, incisional surgical wound infections also had a significant prolongation of stay (median 10 days longer). Staphylococcus aureus was the most important pathogen associated with surgical wound infections (SWIs). Phage typing of 29 strains causing SWI showed only two identical pairs, so only a minority of infections could be explained by cross-infection. Older age, and more complicated procedures (e.g. cardiac valve operations) were independent, statistically significant, risk factors for the development of PI. Since there is a progressive trend towards operating on older patients and performing more complicated procedures, the incidence of PI is expected to increase. Therefore it will become increasingly important to develop new strategies to prevent these serious complications.


Alert override as a habitual behavior - a new perspective on a persistent problem.
Quantifying alert override has been the focus of much research in health informatics, with override rate traditionally viewed as a surrogate inverse indicator for alert effectiveness. However, relying on alert override to assess computerized alerts assumes that alerts are being read and determined to be irrelevant by users. Our research suggests that this is unlikely to be the case when users are experiencing alert overload. We propose that over time, alert override becomes habitual. The override response is activated by environmental cues and repeated automatically, with limited conscious intention. In this paper we outline this new perspective on understanding alert override. We present evidence consistent with the notion of alert override as a habitual behavior and discuss implications of this novel perspective for future research on alert override, a common and persistent problem accompanying decision support system implementation.


Prevention and handling of complications of renal focal therapies.
Small renal lesions often confer relatively low oncologic risk and, as such, dictate for treatment strategies with low morbidity. Minimally invasive ablative techniques have been developed and can deliver good outcomes where used judiciously. The potential risks of treatment relate to the method of ablation, the route by which it is delivered, together with patient and tumor factors. The complications associated with radiofrequency ablation and cryoablation, delivered via percutaneous and laparoscopic approaches, are considered in this review. Percutaneous ablation appears to be associated with lower rates of morbidity but higher rates of recurrence when compared with laparoscopic ablation. The ability to dissect the lesion away from surrounding structures is limited with the percutaneous approach, which can lead to poor outcomes when treating lesions close to the ureter or hilum. Hemorrhagic complications that are seen with laparoscopic cryoablation are most often associated with tumor fracture during the freeze-thaw cycle. This is encountered most frequently in larger, peripheral lesions but may be mitigated by slowing the freeze rate. Postablation inpatient stays are often short, and early signs of complication are often nonspecific. This combination can lead to significant delay in the recognition of postablative problems with a resultant increase in morbidity. A high index of suspicion together with appropriate use of imaging allows for earlier detection and management of complications.


Neural transdifferentiation of human bone marrow mesenchymal stem cells on hydrophobic polymer-modified surface and therapeutic effects in an animal model of ischemic stroke.
Human bone marrow-derived mesenchymal stem cells (MSCs) have multi-lineage differentiation potential and can become cells of mesodermal and neural lineages. These stem cells thus hold considerable clinical promise for the treatment of neurodegenerative diseases. For successful regeneration of damaged neural tissues, directed differentiation of neural or neuronal precursor cells from MSCs and integration of transplanted cells are pivotal factors. We induced MSCs into neurogenesis using a modified protocol. The therapeutic potency of the resulting neural progenitor cells in a rat model of ischemic stroke was analyzed. Using a highly hydrophobic diphenylamino-s-triazine-bridged p-phenylene (DTOPV)-coated surface and adopting a procedure for propagation of neural stem cells, we efficiently converted MSCs into neurosphere-like cellular aggregates (NS-MSCs). The spherical cells were subsequently induced to differentiate into neural cells expressing neuroectodermal markers. To determine whether these cells had neuronal fates and induced neuro-protective effects in vivo, NS-MSCs were intra-cerebrally administered to rats 48h after permanent middle cerebral artery occlusion (pMCAo). The results showed a remarkable attenuation of ischemic damage with significant functional recovery, although the cells were not fully incorporated into the damaged tissues on post-operative day 26. Improvement in the NS-MSC-transplanted rats was faster than in the MSC group and suppression of inflammation was likely the key factor. Thus, our culture system using the hydrophobic surface of a biocompatible DTOPV coating efficiently supported neural cell differentiation from MSCs. Neural-primed MSCs exhibited stronger therapeutic effects than MSCs in rat brains with pMCAo.


A randomized, double-blind, placebo-controlled study of oral coenzyme Q10 to relieve self-reported treatment-related fatigue in newly diagnosed patients with breast cancer.
Coenzyme Q10 (CoQ10) is a common antioxidant supplement with known cardioprotective effects and potential anticancer benefits. We performed a randomized, double-blind, placebo-controlled study of oral CoQ10 in female breast cancer patients with the primary objective of determining CoQ10's effects on self-reported fatigue, depression, and quality of life (QOL). Methods Eligible women with newly diagnosed breast cancer and planned adjuvant chemotherapy were randomized to oral supplements of 300 mg CoQ10 or placebo, each combined with 300 IU vitamin E, divided into 3 daily doses. Treatment was continued for 24 weeks. Blood tests, QOL measures, and levels of plasma CoQ10 and vitamin E were obtained at baseline and at 8, 16, and 24 weeks. Mixed-effects models were used to assess treatment differences in outcomes over time. Between September 2004 and March 2009, 236 women were enrolled. Treatment arms were well balanced with respect to age (range, 28-85 years), pathologic stage (stage 0, 91%; stage 1, 8%; stage II, 1%), ethnicity (white, 87%; black, 11%; Hispanic, 2%), and planned therapy. Baseline CoQ10 levels in the CoQ10 and placebo arms were 0.70 and 0.73 microg/mL, respectively; the 24-week CoQ10 levels were 1.83 and 0.79 microg/mL, respectively. There were no significant differences between the CoQ10 and placebo arms at 24 weeks for scores on the Profile of Mood States-Fatigue questionnaire (least squares means, 7.08 vs 8.24, P = .257), the Functional Assessment of Chronic Illness Therapy-Fatigue tool (37.6 vs 37.6, P = .965), the Functional Assessment of Cancer Therapy-Breast Cancer instrument (111.9 vs 110.4, P = .577), or the Center for Epidemiologic Studies-Depression scale (11.6 vs 12.3, P = .632). Supplementation with conventional doses of CoQ10 led to sustained increases in plasma CoQ10 levels but did not result in improved self-reported fatigue or QOL after 24 weeks of treatment.


Coping with coping strategies: how distributed teams and their members deal with the stress of distance, time zones and culture.
The changing world of work is increasing demands on workers through greater need for flexibility in global collaboration. This multiple-case study uses a qualitative research approach to study context-specific job stressors and coping in ten geographically distributed work teams. Results demonstrate the complex and dynamic nature of the stress-coping process and how coping strategies, adapted to manage stress-evoking uncertainty and ambiguity in distributed work, created secondary sources of psychological strain to individuals. The main strategies for managing the uncertainty and ambiguity in the studied teams were extensive emailing, travelling to face-to-face meetings and extending workdays to collaborate simultaneously across time zones. Continuously used, these coping strategies created work overload and strain. Experienced workers, who had good self-management skills, succeeded in coping with these secondary sources of strain by prioritizing and setting clear limits for workload. Less-experienced workers were overloaded and needed more social support from their leaders and teammates. The study proposes that distributed team members rely heavily on individual coping resources, because spatial and temporal distance hinders or even precludes the mobilization of social resources related to emotional, instrumental and informational social support.


[Differential diagnosis of hereditary and acquired progenic forms of bite].
The article deals with problems of differential diagnosis of acquired and inborn hereditary progenies. The frequency of progenies in aggravated families is 28.2% and in the familes without aggravation it is 10.9% (p less than 0.01). The dominant type of inheritance is determined according to the genealogical tree. Progenies of recessive hereditary nature should be differentiated from the dominant type of "slipping through" generation. From the point of view of prediction, hereditary progenies are more unfavourable than the acquired ones because of frequent relapses, and their treatment should be undertaken at an early stage.


Distinct memory CD4+ T-cell subsets mediate immune recognition of Epstein Barr virus nuclear antigen 1 in healthy virus carriers.
CD4+ T cells, specific for transforming latent infection with the Epstein Barr virus (EBV), consistently recognize the nuclear antigen 1 of EBV (EBNA1). EBNA1-specific effector CD4+ T cells are primarily T-helper 1 (TH1) polarized. Here we show that most healthy EBV carriers have such IFN-secreting EBNA1-specific CD4+ T cells at a frequency of 0.03% of circulating CD4+ T cells. In addition, healthy carriers have a large pool of CD4+ T cells that proliferated in response to EBNA1 and consisted of distinct memory-cell subsets. Despite continuous antigen presence due to persistent EBV infection, half of the proliferating EBNA1-specific CD4+ T cells belonged to the central-memory compartment (TCM). The remaining EBNA1-specific CD4+ T cells displayed an effector-memory phenotype (TEM), of which a minority rapidly secreted IFN upon stimulation with EBNA1. Based on chemokine receptor analysis, all EBNA1-specific TCM CD4+ T cells were TH1 committed. Our results suggest that protective immune control of chronic infections, like EBV, includes a substantial reservoir of TCM CD4+ TH1 precursors, which continuously fuels TH1-polarized effector cells.


In Vivo Effects of Tea Polyphenol Intake on Human Intestinal Microflora and Metabolism.
Effects of tea polyphenol intake (0.4 g/volunteer, 3 times per day, for four weeks) on fecal microflora, bacterial metabolites, and pH were investigated using eight healthy human volunteers. Counts for Clostridium perfringens and other Clostridium spp. were significantly decreased during the tea polyphenol intake periods. Percentage of volunteers having C. perfringens in their feces decreased significantly, but not for other Clostridium spp. Percentage of Bifidobacterium spp. (the acid forming bacteria) in total counts and the content of volatile fatty acids including acetic and propionic acids increased significantly, which might have reduced the fecal pH. However, the tea polyphenols had no effect on fecal enzyme activities, ammonia, or putrefactive products. Two weeks after discontinuing the intake, the microflora counts and their biological parameters appeared to have returned to normal.


Current outcomes in islet versus solid organ pancreas transplant for β-cell replacement in type 1 diabetes.
With continued optimization of islet isolation and immunosuppression protocols, the medium-term rates of insulin independence following islet transplantation have improved significantly. This review evaluates the most up-to-date outcomes data for both solid organ pancreas and islet transplantation to develop an algorithm for selection of β-cell replacement in type 1 diabetes patients. Solid organ pancreas and islet transplantation have both displayed improved rates of 5-year insulin independence, largely attributable to improvements in immunosuppressive regimens. The medium-term rates of insulin independence following islet transplantation in highly selected type 1 nonuremic diabetic recipients is beginning to approach the success rates observed following solitary pancreas transplantation. Although pancreas transplantation has historically been favored for β-cell replacement, current outcomes following islet transplantation justify the use of this minimally invasive therapy in carefully selected patients. Pancreas transplant remains the procedure of choice for β-cell replacement in uremic patients. Islet transplantation should be considered in nonuremic patients with low BMI and low insulin requirements, patients lacking the cardiovascular reserve to undergo open abdominal surgery, or patients who elect to forego the risks of a major operation in exchange for an increased risk of islet graft failure.


Effect of seaweed extracts on Streptococcus sobrinus adsorption to saliva-coated hydroxyapatite.
The inhibitory effect of the extracts of seaweeds on the adsorption of Streptococcus sobrinus B13 to the tooth surface was investigated in vitro. Using saliva-coated hydroxyapatite beads (S-HA) as experimental salivary pellicle, extracts from Gloiopeltis furcata and Gigartina teedii (Rhodopheceae) strongly inhibited the adsorption of S. sobrinus B13 to S-HA. The G. furcata extract, which strongly inhibited the adsorption of S. sobrinus B13 to S-HA, was a high molecular weight sulfated polysaccharide. The result of I.R. analysis indicated that the active component in this extract of G. furcata was funoran.


The relationship between Insulin-like Growth Factor 1, sex steroids and timing of the pubertal growth spurt.
Progress through puberty involves a complex hormonal cascade, but the individual contributions of hormones, particularly IGF-1, are unknown. We reanalysed Chard growth study data to explore the tempo of puberty based on changes in both height and hormone levels, using a novel method of growth curve analysis. Schoolboys (n = 54) and girls (n = 70) from Chard, Somerset, England, recruited in 1981 at age 8/9 and followed to age 16. Every 6 months, height and Tanner stages (genitalia, breast, pubic hair) were recorded, and in a subsample (24 boys, 27 girls), blood samples were taken. Serum IGF-1, testosterone (boys) and oestradiol (girls) were measured by radioimmunoassay. Individual growth curves for each outcome were analysed using variants of the super-imposition by translation and rotation (SITAR) method, which estimates a mean curve and subject-specific random effects corresponding to size, and age and magnitude of peak velocity. The SITAR models fitted the data well, explaining 99%, 65%, 86% and 47% of variance for height, IGF-1, testosterone and oestradiol, respectively, and 69-88% for the Tanner stages. During puberty, the variables all increased steeply in value in individuals, the ages at peak velocity for the different variables being highly correlated, particularly for IGF-1 vs height (r = 0·74 for girls, 0·92 for boys). IGF-1, like height, the sex steroids and Tanner stages, rises steeply in individuals during puberty, with the timings of the rises tightly synchronized within individuals. This suggests that IGF-1 may play an important role in determining the timing of puberty.


Supramolecular Nanosystem Based on Pillararene-Capped CuS Nanoparticles for Targeted Chemo-Photothermal Therapy.
A smart supramolecular nanosystem integrating targeting, chemotherapy, and photothermal therapy was constructed based on carboxylatopillar[5]arene (CP[5]A)-functionalized CuS nanoparticles (CuS@CP NPs). CuS@CP NPs with good monodispersibility and strong near-infrared absorption were synthesized in aqueous solution through a facile one-pot supramolecular capping method, followed by surface installation of a liver cancer-targeted galactose derivative through host-guest binding interaction. The resulting smart supramolecular nanosystem, namely, CuS@CPG, exhibited excellent photothermal ablation capability to HepG2 cells upon irradiation with laser at 808 nm. Chemotherapeutic drug, doxorubicin hydrochloride (DOX), was further loaded on CuS@CPG via electrostatic interactions between positively charged DOX and negatively charged CP[5]A to give CuS@CPG-DOX with a high drug-loading capacity up to 48.4%. The weakening of DOX-CP[5]A interactions in an acidic environment promoted the pH-responsive drug release from CuS@CPG-DOX. Significantly, this multifunctional supramolecular nanosystem showed a remarkably enhanced therapeutic effect through the combination of targeted chemotherapy and photothermal therapy upon in vitro cell study. Moreover, preliminary in vivo study demonstrated that CuS@CPG and CuS@CPG-DOX had good biocompatibility and excellent tumor inhibition effects upon near-infrared laser irradiation.


Prevalence of xylazine in overdose cases: An analysis of Miami-Dade County medical examiner case data.
Xylazine sedative, muscle relaxant, and analgesic used in a veterinary setting. Although xylazine was never approved for therapeutic use in humans, it has become popular in the street drug market as a cutting or bulking agent in the fentanyl and heroin supply. Recently, there has been a significant increase in the detection of xylazine in postmortem forensic toxicology casework. Xylazine can be identified during routine toxicology screening utilizing instrumentation such as gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. Using the Miami-Dade Medical Examiner's LIMS system, all cases received between 2015 and 2022 in which xylazine was reported were reviewed. The cases studied include accidental drug overdose deaths in Miami-Dade County as well as Collier County (Naples), Florida. In total, there are 170 cases; the majority are accidental polydrug overdoses involving White males between the ages of 25 and 44 years old. Of the 170 cases, 37% listed xylazine as the cause of death. 13% of cases contained only xylazine and fentanyl while the remaining 87% of deaths were attributed to polydrug toxicity involving two or more substances. The prevalence of xylazine can be attributed to its increasing popularity rather than an increase in caseload. In 2019, xylazine was present in only 4% of all accidental fentanyl overdoses. By 2021, this percentage has increased sixfold, with xylazine present in 24% of all accidental fentanyl overdoses. Despite a decrease in fentanyl overdoses in 2022, the percentage of xylazine detection remained the same.


Algorithms for optimizing drug therapy.
Drug therapy has become increasingly efficient, with more drugs available for treatment of an ever-growing number of conditions. Yet, drug use is reported to be sub optimal in several aspects, such as dosage, patient's adherence and outcome of therapy. The aim of the current study was to investigate the possibility to optimize drug therapy using computer programs, available on the Internet. One hundred and ten officially endorsed text documents, published between 1996 and 2004, containing guidelines for drug therapy in 246 disorders, were analyzed with regard to information about patient-, disease- and drug-related factors and relationships between these factors. This information was used to construct algorithms for identifying optimum treatment in each of the studied disorders. These algorithms were categorized in order to define as few models as possible that still could accommodate the identified factors and the relationships between them. The resulting program prototypes were implemented in HTML (user interface) and JavaScript (program logic). Three types of algorithms were sufficient for the intended purpose. The simplest type is a list of factors, each of which implies that the particular patient should or should not receive treatment. This is adequate in situations where only one treatment exists. The second type, a more elaborate model, is required when treatment can by provided using drugs from different pharmacological classes and the selection of drug class is dependent on patient characteristics. An easily implemented set of if-then statements was able to manage the identified information in such instances. The third type was needed in the few situations where the selection and dosage of drugs were depending on the degree to which one or more patient-specific factors were present. In these cases the implementation of an established decision model based on fuzzy sets was required. Computer programs based on one of these three models could be constructed regarding all but one of the studied disorders. The single exception was depression, where reliable relationships between patient characteristics, drug classes and outcome of therapy remain to be defined. Algorithms for optimizing drug therapy can, with presumably rare exceptions, be developed for any disorder, using standard Internet programming methods.


MANDATING DISCLOSURE OF CONSCIENCE-BASED LIMITATIONS ON MEDICAL PRACTICE.
Stakeholders in law, medicine, and religion are unable to reach consensus about how best to address conflicts between healthcare providers' conscientious objections to treatment and patients' rights to access medical care. Conscience laws that protect objecting providers and institutions from liability are criticized as too broad by patient advocates and as too narrow by defenders of religious freedom. This Article posits that some of the tension between these stakeholders could be mitigated by statutory recognition of a duty on the part of healthcare institutions or providers to disclose conscientiously motivated limitations on practice. While this solution would not guarantee a patient's access to treatment, referral, or information from any given provider, it would prevent some of the more egregious cases of denial of treatment--those where patients are not made aware that a legal and clinically defensible treatment option is excluded from a provider's or institution's scope of practice and so have no opportunity to seek care elsewhere.


The application of moist dressing in treating burn wound.
Basic experiments have demonstrated that the effect of wound healing in moist environments is better than that in dry environments; therefore, research on moist dressing is the focus of wound healing research. 42 burn patients receiving treatment in Jiangsu Provincial People's Hospital were selected as experimental cases. Wound surface is divided into treatment group and control group using a self-contrasted method. The treatment group received a moist dressing in the treatment of burn wounds and the control group adopted iodine gauze or Vaseline gauze coverage. Wound healing effect and the impact on the degree of pain of in the two different treatment methods were observed after treatment. The results of 42 patients were included in the analysis. The average healing time of patients' burn wounds in treatment group is (10.9 3.3) d, and the average healing time in control group is (13.8 3.6) d, so, the difference is significant (P<0.01). Wound pain in the treatment group is significantly lower than that in the control group (P<0.01). Using moist dressing (Mepitel and Mepilex, etc.) in the treatment of burn wounds, wound-healing time can be shortened and wound pain can be reduced significantly.


Influence of the Cation Adducts in the Analysis of Matrix-Assisted Laser Desorption Ionization Imaging Mass Spectrometry Data from Injury Models of Rat Spinal Cord.
Imaging mass spectrometry (IMS) is quickly becoming a technique of reference to visualize the lipid distribution in tissue sections. Still, many questions remain open, and data analysis has to be optimized to avoid interpretation pitfalls. Here we analyze how the variation on the [Na+]/[K+] relative abundance affects the detection of lipids between sections of spinal cord of (uninjured) control rats and of models of spinal cord demyelination and traumatic contusion injury. The [M + Na]+/[M + K]+ adducts ratio remained approximately constant along transversal and longitudinal sections of spinal cord from control animals, but it strongly changed depending on the type of lesion. A substantial increase in the abundance of [M + Na]+ adducts was observed in samples from spinal cord with demyelination, while the intensity of the [M + K]+ adducts was stronger in those sections from mechanically injured spinal cords. Such changes masked the modifications in the lipid profile due to the injury and only after summing the signal intensity of all adducts and corresponding monoprotonated molecular ions of each detected lipid in a single variable, it was possible to unveil the real changes in the lipid profile due to the lesion. Such lipids included glycerophospholipids (both diacyl and aryl-acyl), sphingolipids, and nonpolar lipids (diacyl and triacylglycerols), which are the main lipid classes detected in positive-ion mode. Furthermore, the results demonstrate the sensitivity of the technique toward modification in tissue homeostasis and that the [M + Na]+/[M + K]+ ratio may be used to detect alterations in such homeostasis.


Remote Robotic Surgery and Virtual Education Platforms: How Advanced Surgical Technologies Can Increase Access to Surgical Care in Resource-Limited Settings.
Advanced surgical technologies consist of remote and virtual platforms that facilitate surgical care and education. It also includes the infrastructure necessary to utilize these platforms (e.g., internet access, robotic systems, and simulators). Given that 5 billion people lack access to safe and timely surgical care, the appeal of these technologies to the field of global surgery lies primarily in its ability to eliminate geographical barriers and address surgeon shortages. This article discusses the use of virtual and remote technologies in resource-limited settings, the potential applications of these technologies, the possible barriers to their integration, and the impact these technologies may have on access to surgical care and education. Specifically, it will explore how robotic surgery, telesurgery, virtual education platforms, and simulations have the potential to be instrumental in enhancing worldwide access to safe surgical care.


Disseminated Mycobacterium scrofulaceum Infection in an Immunocompetent Host.
A 56-year-old woman, without any immunocompromising diseases, was referred to our hospital because of a recurrence of pyogenic spondylitis. Computed tomography revealed multiple osteolytic changes in the whole body. Vertebral magnetic resonance imaging revealed osteomyelitis and spondylitis. Mycobacterium scrofulaceum was detected in sputum cultures, in abscesses from the right knee, and in a subcutaneous forehead abscess. Therefore, the patient was diagnosed with disseminated Mycobacterium scrofulaceum infection. The patient was treated with rifampicin, ethambutol, and clarithromycin, which resulted in symptomatic relief and radiological improvement. We herein report a rare case of disseminated Mycobacterium scrofulaceum infection in an immunocompetent host.


Removal of Trace Uranium from Groundwaters Using Membrane Capacitive Deionization Desalination for Potable Supply in Remote Communities: Bench, Pilot, and Field Scale Investigations.
The performance of membrane capacitive deionization (MCDI) desalination was investigated at bench, pilot, and field scales for the removal of uranium from groundwater. It was found that up to 98.9% of the uranium can be removed using MCDI from a groundwater source containing 50 μg/L uranium, with the majority (94.5%) being retained on the anode. Uranium was found to physiochemically adsorb to the electrode without the application of a potential by displacing chloride ions, with 16.6% uranium removal at the bench scale via this non-electrochemical process. This displacement of chloride did not occur during the MCDI adsorption phase with the adsorption of all ions remaining constant during a time series analysis on the pilot unit. For the scenarios tested on the pilot unit, the flowrate of the product water ranged from 0.15 to 0.23 m3/h, electrode energy consumption from 0.28 to 0.51 kW h/m3, and water recovery from 69 to 86%. A portion (13-53% on the pilot unit) of the uranium was found to remain on the electrodes after the brine discharge phase with conventional cleaning techniques unable to release this retained uranium. MCDI was found to be a suitable means to remove uranium from groundwater systems though with the need to manage the accumulation of uranium on the electrodes over time.


Cost-Efficiency Analysis of the Improved Web-Based Planning, Budgeting, and Reporting System (PlanRep) in Tanzania.
Information systems offer unlimited potential for innovation and digitalization of management functions to facilitate citizen participation and improve accountability, transparency, and efficiency in government operations and service delivery. In line with this, for more than one decade, Tanzania implemented an integrated planning, budgeting, and reporting system (PlanRep) that was used to prepare plans and budgets at the local government authorities (LGAs) using a desktop application. In 2017, PlanRep was upgraded to a Web-based system to address several challenges, including poor coordination and high cost involved in the preparation of plans and budgets. However, operational evidence regarding the cost-efficiencies and benefits of shifting to Web-based PlanRep has not been explored. This study aims to address this gap by assessing efficiency gains (in terms of cost and time) of shifting to a Web-based PlanRep system as a tool for the preparation of LGA plans and budgets. The study applied a retrospective before-and-after study design whereby quantitative data was used to assess the amount of time and the cost incurred by LGAs when preparing their budget 1 year before the introduction of PlanRep and 1 year after. Parallelly, qualitative data were collected through key informant interviews with selected LGA officials, Regional Secretariats (RSs), President's Office Regional Administration and Local Government (PORALG), and system end-users such as heads of health facilities and schools (primary and secondary). Secondary data was analyzed by comparing time and cost used before and after Web-based PlanRep, while thematic analysis was employed for qualitative data. The analysis showed a 53% reduction (from USD 3.8 million in 2017/18 to USD 1.8 million in 2018/19) in the total costs LGAs incurred during planning and budgeting after introducing the Web-based PlanRep. The main efficiency gain was related to per diem costs. The analysis also showed significant time saving from an average of 87 days in 2017/18 to only 8 days in 2018/19. PlanRep system end-users also acknowledged that the introduction of Web-based PlanRep has significantly saved their time and costs in preparation of LGA plans and budget. The introduction of the Web-based planning, budgeting, and reporting systems has resulted in tremendous cost reduction, time savings, transparency, accountability, and workload reduction. The findings offer operational evidence to guide the implementation and scale up of similar systems in countries that share equivalent circumstances like Tanzania.


Value of complete full-length lower extremity sonography in patients undergoing computed tomographic pulmonary angiography.
To evaluate the diagnostic yield of complete lower extremity venous sonography for diagnosing deep venous thrombosis (DVT) in patients undergoing computed tomographic (CT) pulmonary angiography for suspected pulmonary embolism (PE). We retrospectively reviewed all cases of lower extremity venous sonography and CT pulmonary angiography performed within 1 day of each other (n = 147) in a tertiary care center. Indications for the studies performed, angiographic findings, sonographic findings, age, sex, inpatient/outpatient status, lower extremity symptoms, and treatment status were recorded. Prevalence rates and patient characteristics were compared by χ(2) and Fisher exact probability tests where appropriate. Multivariable logistic regression with acute PE as the outcome was performed for age, sex, interval between angiography and sonography, indication for angiography, inpatient/outpatient status, and venous sonographic findings. The prevalence of PE (23.8%) was similar to the prevalence of DVT (27.9%). Angiographic findings were not associated with the interval between angiography and sonography or inpatient/outpatient status. Acute DVT was more likely (P = .0009) when angiographic findings were positive (51.4%), but DVT prevalence was still substantial (20.5%) in patients with negative angiographic findings. Lower extremity symptoms were not associated with DVT in cases with negative angiographic findings (P = .48). Eighteen of the 23 patients with acute DVT and negative angiographic findings were treated. There is a high rate of DVT in a population undergoing CT pulmonary angiography for suspected PE even when PE is not diagnosed. Our data apply to a tertiary care institution, suggest a surveillance bias, and favor the utility of venous sonography in this population.


Pulsatile nature of luteinizing hormone release is maintained during luteinizing hormone-releasing hormone stimulation in normal male rats.
The plasma LH concentration is believed to be reasonably steady in normal male rats. We found that LH is released in a regular pulsatile fashion. The overall mean concentration of plasma LH in normal male rats was 46.6 +/- 4.4 (mean +/- SEM) ng/ml. The normal male rats showed periodic LH pulses: the mean pulse amplitude was 144.4 +/- 25.5 ng/ml and the inter-peak interval was 22.5 +/- 2.0 min. Each pulse lasted 9.7 +/- 0.8 min. When LH-RH (1 microgram/kg) was injected as a bolus, the peak concentration was attained in 10-30 min reaching a peak concentration of 279.4 +/- 39.6 ng/ml. Distinct pulsatile bursts of plasma LH were discernible during the period of elevated plasma LH concentration. When a higher dose of LH-RH (5 micrograms/kg) was administered, the LH concentration slowly increased to a peak concentration of 400.2 +/- 38.7 ng/ml in 20-40 min. The pulsatile nature of the LH concentration was recognizable with distinct bursts. We have observed that: (a) normal male rats release LH in a pulsatile fashion with an approximate 20-min inter-peak interval; (b) mean LH pulses last less than 10 min, and (c) the LH pulses are visible even with elevated LH and LH-RH concentrations in the general circulation.


[Advanced in solubilization methods of water-insoluble natural drugs].
With the development of natural products, the research activities on the solubilization methods of water-insoluble natural products have been carried out worldwide. Big molecular weight and poor solubility of most natural active ingredients lead to a very poor oral absorption and low bioavailability, which has extremely limited their development in pharmaceutical fields and clinical application. As a result, it is necessary to find out a suitable technique to improve the solubility and enhance the oral bioavailability of insoluble natural drugs. Based on the related references published in these years, this review introduced some new techniques to improve the solubility and bioavailability of natural drugs, including prodrugs, inclusion complex, solid dispersion, cocrystals, osmotic pump, liquisolid compacts, micronization, self-microemulsifying, nanosuspensions, lipsomes, polymeric micelles and so on, and summarized the theory, characteristics, application range, application examples, problems and development direction of each technique.


A conducting polymer film stronger than aluminum.
Polythiophene (Pth) was electrochemically deposited onto stainless steel substrate from freshly distilled boron fluoride-ethyl ether containing 10 millimoles of thiophene per liter. The free-standing Pth film obtained at an applied potential of 1.3 volts (versus Ag/AgCl) had a conductivity of 48.7 siemens per centimeter. Its tensile strength (1200 to 1300 kilograms per square centimeter) was greater than that of aluminium (1000 to 1100 kilograms per square centimeter). This Pth film behaves like a metal sheet and can be easily cut into various structures with a knife or a pair of scissors.


Effects of recombinant human granulocyte colony-stimulating factor on the hematologic recovery and survival of irradiated mice.
We studied the effects of intraperitoneal injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF) according to various administration schedules on the recovery of spleen colony-forming units (CFU-S) and peripheral blood counts, and on the survival of irradiated mice. The sooner and more frequently the mice were injected with rhG-CSF after irradiation, the more enhanced the recovery of CFU-S in bone marrow was obtained on day 7. Twice-daily injections of rhG-CSF from day 0 to day 2 significantly enhanced the recovery of platelets and hematocrit, but two injections of rhG-CSF on only day 0 did not. Twice-daily injections of rhG-CSF from day 0 to day 6 enhanced the recovery of platelets more effectively than twice-daily injections of rhG-CSF from day 1 to day 7, and increased the survival of irradiated mice more effectively than any other examined administration schedules. Twice-daily injections of rhG-CSF from day 0 to day 6 were significantly effective in enhancing the survival of mice irradiated with 8.5-, 9.0-, and 9.5-Gy x-rays, although not effective after irradiation of 10.5-Gy x-rays.


Hepatic schistosomiasis with massive splenomegaly: a case report and literature review.
Schistosomiasis is a parasitic disease caused by Schistosoma species. Intestinal and hepatic schistosomiases are the most common forms of chronic disease. We describe a case of a 26-year old patient from Eritrea who was referred to our hospital with abdominal pain and diarrhea. The diagnosis of hepatosplenic schistosomiasis was made by liver biopsy and the patient was treated with praziquantel. Hepatic schistosomiasis is characterised by deposition of schistosomal eggs in the liver which results in a host cell immune response and leads to granuloma formation and neoangiogenesis. This is hallmarked by different grades of periportal fibrosis with portal hypertension leading to splenomegaly. Normal liver architecture is preserved and periportal fibrosis can be reversible if treated adequately and timely. With a recent native schistosomiasis cluster report from France and the expected influx to Europe of persons from regions endemic for schistosomiasis, increased awareness of this disease in healthcare practitioners is needed. We review the epidemiology, pathogenesis, clinical presentation and treatment of schistosomiasis.


Prognostic significance of adrenal gland morphology at CT in patients with three common malignancies.
To determine whether minor alterations in adrenal gland morphology at baseline CT in three common cancers indicate early metastasis. 689 patients (237 with lung cancer, 228 with breast cancer, 224 with melanoma) underwent baseline and follow-up CTs that included the adrenals. Two readers independently scored each adrenal at baseline CT as normal, smoothly enlarged, nodular or mass-containing. Adrenals containing a mass >10 mm were excluded. The appearance of each adrenal on the latest available CT was assessed for change since baseline. Cox models were used to assess the association between adrenal morphology at initial CT and subsequent development of adrenal metastasis (defined as new mass >10 mm, corroborated by follow-up imaging). κ statistics were calculated to assess inter-reader agreement. Initial and follow-up CT evaluations were recorded for 1317 adrenals (median follow-up, 18.6 months). At initial CT, Readers 1 and 2 interpreted 1242 and 1230 adrenals as normal, 40 and 57 as smoothly enlarged, 29 and 25 as nodular, and 6 and 5 as containing masses ≤ 10 mm, respectively. κ-values were 0.52 (moderate) at initial CT and 0.70 (substantial) at follow-up. The hazard ratio for developing a metastasis at follow-up CT given an abnormal adrenal assessment at baseline was 0.7 [95% confidence interval (CI) 0.2-2.1; p = 0.47] for Reader 1, and 2.0 (95% CI 0.8-4.7; p = 0.12) for Reader 2. Minor morphological abnormalities of adrenals at initial CT did not represent early adrenal metastasis in most patients in this population.


CRISPR-Cas9: From a bacterial immune system to genome-edited human cells in clinical trials.
The adaptive bacterial immune system CRISPR-Cas is revolutionizing all fields of life science and has opened up new frontiers toward personalised medicine. Since the elucidation of the molecular mechanism of Cas9 from Streptococcus pyogenes in 2012 and its development as a genomic engineering tool, genetic modifications in more than 40 species have been performed, over 290 patents have been filed worldwide and the first clinical trials using CRISPR-Cas-modified T-cells have recently been started in China and in the US. In this review we summarise current design developments, novel Cas systems and their antagonists, present and potential future applications as well as the ongoing debate on ethical issues, which has arisen through the CRISPR-Cas technology.


Chemotaxonomy of the Oleaceae: iridoids as taxonomic markers.
The distribution and biosynthesis of iridoid glucosides in the Oleaceae is reviewed and five distinct biosynthetic pathways to iridoids have been identified in the family, deoxyloganic acid apparently being a common intermediate. Likewise, the distributions of caffeoyl phenylethanoid glycosides (CPGs), i.e. verbascoside and its analogues, as well as cornoside are listed. Iridoid glucoside data exist for 17 genera of Oleaceae and the occurrence of iridoids from the different biosynthetic pathways correlate extremely well with the phylogenetic classification inferred from recent chloroplast DNA sequence data. Thus the tribe Fontanesieae (Fontanesia) contains "normal" secoiridoids, Forsythieae (Abeliophyllum, Forsythia) contains cornoside and/or iridoids from the forsythide pathway, Myxopyreae (Myxopyrum, Nyctanthes) have iridoids from the myxopyroside pathway, and finally, the two tribes Jasmineae and Oleeae (the remaining genera) both contain iridoids from the oleoside pathway. Within Jasmineae, one group of Jasminum sp. is characterized by the presence of jasminin or similar compounds, while another group of Jasminum species and Menodora display derivatives of 10-hydroxyoleoside, compounds not present in the other group. CPGs are reported from about half of the species investigated. With regard to taxonomy at the order level, the chemical data might support a position within or close to Lamiales due to the common presence of CPGs, the iridoids being of less significance since they are of a type that are barely found elsewhere.


Stereopsis after implantation of intraocular lens in patients under 40 years old with unilateral cataract.
To investigate the stereopsis after single focus intraocular lens (SIOL) implantation in patients aged <40 years with unilateral cataract. In total, 36 patients (36 eyes) were divided into emmetropia and myopia groups. Twenty seven subjects with good uncorrected distance visual acuity (UCDVA) after surgery were enrolled in the emmetropia group. The myopia group consisted of 9 subjects whose one eye had mild myopia postoperatively and the other was emmetropic or myopic. Visual acuity, distance and near stereoacuity were measured post-operatively. In the emmetropia group, uncorrected near visual acuity (UCNVA) did not differ significantly between eyes (t=1.87, P>0.05). The LogMAR UCNVA of the operated and fellow eyes were (0.71±0.12) and (-0.05±0.07, t = 28.4, P<0.001) respectively. Distance stereoacuity was 60"; the near stereoacuity with uncorrected visual acuity and BCNVA in the operated eyes were 200" and 30" respectively (Z=-4.121, P<0.001). In the myopia group, the BCDVA did not differ significantly between the operated and fellow eyes (t =-0.636, P>0.05). The UCNVA of the operated eyes (0.18±0.12) was significantly better compared with that of the fellow eyes (-0.04±0.10, t = 4.2252, P<0.001). The distance stereoacuity with uncorrected visual acuity and BCDVA in the operated eyes were 200" and 60" respectively (Z =-2.371, P<0.05). The near stereoacuity with uncorrected visual acuity was 50". For patients with unilateral cataract aged <40 years, stereopsis is closely associated with refractive status after IOL implantation. Near stereoacuity in emmetropic eyes can be improved with refraction, and that in mildly myopic eyes can be enhanced by leaving myopia uncorrected.


Mitochondrial dynamics and peripheral neuropathy.
Peripheral neuropathy is perhaps the archetypal disease of axonal degeneration, characteristically involving degeneration of the longest axons in the body. Evidence from both inherited and acquired forms of peripheral neuropathy strongly supports that the primary pathology is in the axons themselves and points to disruption of axonal transport as an important disease mechanism. Recent studies in human genetics have further identified abnormalities in mitochondrial dynamics--the fusion, fission, and movement of mitochondria--as a player in the pathogenesis of inherited peripheral neuropathy. This review provides an update on the mechanisms of mitochondrial trafficking in axons and the emerging relationship between the disruption of mitochondrial dynamics and axonal degeneration. Evidence suggests mitochondria are a "critical cargo" whose transport is necessary for proper axonal and synaptic function. Importantly, understanding the regulation of mitochondrial movement and the consequences of decreased axonal mitochondrial function may define new paths for therapeutic agents in peripheral neuropathy and other neurodegenerative diseases.


Disease course after the first recurrence of head and neck squamous cell carcinoma following (chemo)radiation.
Recurrent head and neck squamous cell carcinoma (HNSCC) after chemoradiation is a challenging clinical problem. Salvage surgery (SS) is often extensive and mutilating. Oncological outcomes of SS are relatively well known, but little is published about the course of disease after the first recurrence, especially in patients without salvage possibilities. The aim of this study was to analyze the course of disease in patients with recurrent HNSCC after chemoradiation. We retrospectively analyzed and descriptively reported the disease course in 198 patients with recurrent HNSCC after chemoradiation in the time period after the first recurrence. We scored any type of event, salvage treatment, systemic treatment and overall survival (OS). Of the 198 patients with recurrent HNSCC, salvage surgery was attempted in 104 (53%). SS was more frequently given in patients with recurrent laryngeal cancer, isolated regional failure (p < 0.001) and HPV-positive disease (p = 0.09). The 2-year OS of the whole group was 31% and was significantly different by tumor site, type of failure and SS. HPV-positive disease and salvaged recurrences were significantly predictive for better survival. One third of that salvaged patients was still alive without second recurrence. Median survival in patients that received any palliative systemic treatment without surgery, compared to those were no treatment was given, was 6 and 3 months, respectively (p = 0.006). Main factors influencing the course of disease in recurrent HNSCC are the possibilities for SS and HPV-status. Therefore, SS should always be considered and discussed. In patients without possibilities for SS, overall survival is 3-6 months.


Climate Change Modulates Multitrophic Interactions Between Maize, A Root Herbivore, and Its Enemies.
How climate change will modify belowground tritrophic interactions is poorly understood, despite their importance for agricultural productivity. Here, we manipulated the three major abiotic factors associated with climate change (atmospheric CO2, temperature, and soil moisture) and investigated their individual and joint effects on the interaction between maize, the banded cucumber beetle (Diabrotica balteata), and the entomopathogenic nematode (EPN) Heterorhabditis bacteriophora. Changes in individual abiotic parameters had a strong influence on plant biomass, leaf wilting, sugar concentrations, protein levels, and benzoxazinoid contents. Yet, when combined to simulate a predicted climate scenario (Representative Concentration Pathway 8.5, RCP 8.5), their effects mostly counter-balanced each other. Only the sharp negative impact of drought on leaf wilting was not fully compensated. In both current and predicted scenarios, root damage resulted in increased leaf wilting, reduced root biomass, and reconfigured the plant sugar metabolism. Single climatic variables modulated the herbivore performance and survival in an additive manner, although slight interactions were also observed. Increased temperature and CO2 levels both enhanced the performance of the insect, but elevated temperature also decreased its survival. Elevated temperatures and CO2 further directly impeded the EPN infectivity potential, while lower moisture levels improved it through plant- and/or herbivore-mediated changes. In the RCP 8.5 scenario, temperature and CO2 showed interactive effects on EPN infectivity, which was overall decreased by 40%. We conclude that root pest problems may worsen with climate change due to increased herbivore performance and reduced top-down control by biological control agents.


The effectiveness of telemedicine interventions on women with postpartum depression: A systematic review and meta-analysis.
Postpartum depression (PPD) is a public health problem that has significant adverse effects on mothers, couple's relationships, newborn neurodevelopment, and child emotional and cognitive development. This study reviewed the effectiveness of telemedicine interventions in postparturient women with postpartum depression. To evaluate the effectiveness of telemedicine intervention in women with postpartum depression. Cochrane Library, PubMed, EMBASE, Web of Science, CINAHL, and PsycINFO were searched for relevant articles published between 2003 and March 2021. We also manually reviewed the reference lists of the retrieved articles. The present study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The risk of bias for individual studies was evaluated according to the Cochrane Handbook. RevMan 5.4 software was used to carry out the meta-analysis. The meta-analysis included 20 randomized controlled trials with a total of 3252 patients. The results demonstrated that telemedicine was an effective intervention for treating PPD and anxiety and for improving functional impairment in women during their postpartum period. This meta-analysis provided evidence that telemedicine was an effective intervention for treating PPD in women. Telemedicine also has significant effects on anxiety and improved functional impairment in women during their postpartum period. Our findings may provide accurate evidence-based guidance for postpartum women's mental health management. In the future, more high-quality studies are required for verifying these results.


Understanding and prevention of "therapy-" induced dyskinesias.
L-dopa is the most effective, currently available treatment for Parkinson's disease (PD), but it leads to the development of involuntary movements known as L-dopa-induced dyskinesia (LID) in the majority of patients after long-term use. Both gene and cell therapy approaches are the subject of multiple ongoing studies as potential ways of relieving symptoms of PD without the complication of dyskinesia. However, the spectre of dyskinesia in the absence of L-dopa, the so-called "off-phase" or graft-induced dyskinesia (GID), remains a major obstacle particularly in the further development of cell therapy in PD, but it is also a concern for proponents of gene therapy approaches. LID results from nonphysiological dopamine release, supersensitivity of dopamine receptors, and consequent abnormal signalling through mechanisms of synaptic plasticity. Restoration of physiological circuitry within the basal ganglia loops is ultimately the aim of all cell and gene therapy approaches but each using distinctive strategies and accompanied by risks of exacerbation of LID or development of "off-phase"/GID. In this paper we discuss the details of what is understood regarding the development of dyskinesias with relevance to cell and gene therapy and potential strategies to minimize their occurrence.


[Comparative morphology of the subphilum Conosa Cavalier-Smith 1998].
Comparative analysis of archamoebae and slime molds morphology revealed that this organisms have a marked similarity in organization of locomotive forms, structure of glycocalix and also in organization of nuclear and flagellar apparatus. A possible scheme of formation the modern diversity of Conosa group was proposed.


S100B and cardiac surgery: possibilities and limitations.
Serum determinations of the glial protein S100B has been found to correlate with brain damage after cardiac surgery. Forty-eight hours and later after surgery, increased S100B levels correlates with the presence of brain infarction, and the extent of infracted brain tissue. S100B at this time-point has been shown to predict long-term outcome, higher S100B levels correlated with decreased survival. Early levels (2-8 hours after surgery) of S100B have shown disparate results when trying to correlate it with postoperative cognitive decline. One reason for the lack of strong correlation could be the contamination of S100B from shed blood the first hours after surgery.


π VAE: a stochastic process prior for Bayesian deep learning with MCMC.
Stochastic processes provide a mathematically elegant way to model complex data. In theory, they provide flexible priors over function classes that can encode a wide range of interesting assumptions. However, in practice efficient inference by optimisation or marginalisation is difficult, a problem further exacerbated with big data and high dimensional input spaces. We propose a novel variational autoencoder (VAE) called the prior encoding variational autoencoder ( π VAE). π VAE is a new continuous stochastic process. We use π VAE to learn low dimensional embeddings of function classes by combining a trainable feature mapping with generative model using a VAE. We show that our framework can accurately learn expressive function classes such as Gaussian processes, but also properties of functions such as their integrals. For popular tasks, such as spatial interpolation, π VAE achieves state-of-the-art performance both in terms of accuracy and computational efficiency. Perhaps most usefully, we demonstrate an elegant and scalable means of performing fully Bayesian inference for stochastic processes within probabilistic programming languages such as Stan.


Imaging Atomic-Scale Clustering in III-V Semiconductor Alloys.
Quaternary alloys are essential for the development of high-performance optoelectronic devices. However, immiscibility of the constituent elements can make these materials vulnerable to phase segregation, which degrades the optical and electrical properties of the solid. High-efficiency III-V photovoltaic cells are particularly sensitive to this degradation. InAlAsSb lattice matched to InP is a promising candidate material for high-bandgap subcells of a multijunction photovoltaic device. However, previous studies of this material have identified characteristic signatures of compositional variation, including anomalous low-energy photoluminescence. In this work, atomic-scale clustering is observed in InAlAsSb via quantitative scanning transmission electron microscopy. Image quantification of atomic column intensity ratios enables the comparison with simulated images, confirming the presence of nonrandom compositional variation in this multispecies alloy.