Overview and implementation of an intervention to prevent adherence failure among HIV-infected adults initiating antiretroviral therapy: lessons learned from Project HEART.
Project HEART, an acronym for Helping Enhance Adherence to Retroviral Therapy, was a prospective, controlled study to develop, implement, and evaluate a clinic-based behavioural intervention to prevent adherence failure among HIV-infected adults beginning their first highly active antiretroviral therapy (HAART) regimen (N = 227). In this paper, we describe the conceptualisation of the Project HEART adherence intervention, characteristics of the participants, and lessons learned implementing HEART in an inner-city clinic setting. A multi-component intervention, HEART combined enhanced education, reminders, adherence feedback, social support and adherence-focused problem solving in an integrated manner to address common cognitive, motivational, and social barriers to adherence. Unique components of the intervention included use of participant-identified adherence support partners and a standardized adherence barriers assessment to develop and implement individualised adherence plans. Lessons learned regarding the feasibility of using participant-identified support partners were as follows. Few participants eligible for the study had trouble identifying a support partner. Over 90% of support partners attended at least one intervention visit. Support partners were most available and amenable to participate early in the initiation of therapy. Participants' experiences as the 'supported' partner were generally positive. Though many participants faced barriers not easily addressed by this intervention (for example, housing instability), formally integrating support partners into the intervention helped to address many other common adherence barriers. Family and friends are an under-utilised resource in HIV medication adherence. Enlisting the help of support partners is a practical and economical approach to adherence counselling.


Neuropeptides with immunoregulatory functions: current status of investigations.
Neuropeptides (NP) from the central nervous system and the peripheral nervous system play a modulating role in the immune system. In principle, all immunological functions are influenced by NP either in terms of nonspecific immunity or cellular immunity. In the present review, some aspects of this interaction are summarized, namely the existence of receptors for NP on immune cells and the production of NP by leukocytes. Finally, the pathogenetic role of NP in diseases and the future perspectives of neuroimmunology are outlined.


Microsurgical and angiographic anatomy of middle cerebral artery aneurysms: prevalence and significance of early branch aneurysms.
To determine the prevalence of early branch aneurysms, characterize these lesions angiographically and anatomically, and determine their clinical significance. The authors conducted a retrospective review of 125 consecutive patients with a diagnosis of middle cerebral artery (MCA) aneurysm. Eighty-four patients harboring 100 MCA aneurysms were studied; 41 patients were excluded for lack of adequate imaging or for fusiform morphology of the aneurysm. Demographic characteristics including age, side, sex, subarachnoid hemorrhage, intracerebral hematoma, multiple aneurysms, and type of treatment were obtained. The average patient age was 57.3 years (range, 29-79 yr); 69 were women and 15 were men. Fifty-eight were right MCA aneurysms and 42 were left aneurysms. Fourteen patients had multiple MCA aneurysms. Thirty-nine of 100 aneurysms were associated with subarachnoid hemorrhage. Twelve of 100 aneurysms were associated with an intracerebral hematoma. The average aneurysm sizes were 9.1 mm overall (range, 2.0-27.0 mm), 12.3 mm for ruptured aneurysms, and 7.5 mm for unruptured. There were 36 M1 bifurcation aneurysms, 39 early frontal branch aneurysms, 18 early temporal branch aneurysms, four lenticulostriate artery aneurysms, and three trifurcation aneurysms. In our retrospective review, the majority of MCA aneurysms arose along the M1 segment proximal to the M1 bifurcation. Early frontal branch aneurysms were more common than typical M1 segment bifurcation aneurysms. M1 segment aneurysms arising from early frontal and early temporal branches have distinct anatomic features that impact surgical management and outcome. Understanding the relationship between the recurrent lenticulostriate arteries arising from the proximal segments of these early branches and the aneurysm neck should allow surgeons to avoid many postoperative ischemic complications when dealing with these challenging lesions.


A 120-kDa alkaline peptidase from Trypanosoma cruzi is involved in the generation of a novel Ca(2+)-signaling factor for mammalian cells.
Trypomastigotes, the infective stages of the intracellular parasite Trypanosoma cruzi, induce rapid and repetitive cytosolic free Ca2+ transients in fibroblasts. Buffering or depletion of intracellular free Ca2+ inhibits cell entry by trypomastigotes, indicating a role for this signaling event in invasion. We show here that the majority of the Ca(2+)-signaling activity is associated with the soluble fraction of parasites disrupted by sonication. Distinct cell types from different species are responsive to this soluble factor, and intracellular free Ca2+ transients occur rapidly and reach concentrations comparable to responses induced by thrombin and bombesin. The Ca(2+)-signaling activity does not bind concanavalin A and is strongly inhibited by a specific subset of protease inhibitors. The only detectable protease in the fractions with Ca(2+)-signaling activity is an unusual alkaline peptidase of 120 kDa, to which no function had been previously assigned. The activity of the protease and cell invasion by trypomastigotes are blocked by the same specific inhibitors that impair Ca(2+)-signaling, suggesting that the enzyme is required for generating the response leading to infection. We demonstrate that the 120-kDa peptidase is not sufficient for triggering Ca(2+)-signaling, possibly being involved in the processing of precursors present only in infective trypomastigotes. These findings indicate a biological function for a previously identified unusual protozoan protease and provide the first example of a proteolytically generated parasite factor with characteristics of a mammalian hormone.


Spectrum of hepatitis E virus infection in India.
A solid phase enzyme linked immunosorbent assay (ELISA) that detects IgM and IgG to hepatitis E virus (HEV) was used to study seroepidemiology in 40 healthy subjects and 227 consecutive patients with liver diseases in an endemic area. Fifty-two of the liver diseases patients (22.9 percent) had acute hepatitis E. In contrast, none of the 40 healthy subjects were positive for IgM anti-HEV, validating the ELISA assay. Twenty-three of 25 (92%) patients with epidemic non-A, non-B hepatitis were confirmed as having acute hepatitis E. Only 1 of the 10 patients with sporadic, fulminant hepatic failure of non-A, non-B, non-C etiology was positive for IgM anti-HEV. Five (31.2%) of the 16 patients with acute hepatitis in HBsAg carriers were positive for IgM anti-HEV. One patient with acute hepatitis B was coinfected with acute hepatitis E. Acute hepatitis was a disease of the adult population, with peak attack rates in the second and third decades of life. This disease was seen in only 4 (16%) of the 25 patients with acute viral hepatitis occurring below 14 years of age. Cholestasis was predominant in 25% of patients, enzyme elevation was monophasic, and all patients had clinical and biochemical recovery from the disease. The data suggest that the majority of patients with acute sporadic non-A, non-B, non-C hepatitis in India have hepatitis E. However, fulminant hepatic failure to sporadic nature is rarely from hepatitis E.


Automated Deformation-Based Analysis of 3D Optical Coherence Tomography in Diabetic Retinopathy.
Diabetic retinopathy (DR) is a significant microvascular complication of diabetes mellitus and a leading cause of vision impairment in working age adults. Optical coherence tomography (OCT) is a routinely used clinical tool to observe retinal structural and thickness alterations in DR. Pathological changes that alter the normal anatomy of the retina, such as intraretinal edema, pose great challenges for conventional layer-based analysis of OCT images. We present an alternative approach for the automated analysis of OCT volumes in DR research based on nonlinear registration. In this paper, we first obtain an anatomically consistent volume of interest (VOI) in different OCT images via carefully designed masking and affine registration. After that, efficient B-spline transformations are computed using stochastic gradient descent optimization. Using the OCT volumes of normal controls, for which layer-based segmentation works well, we demonstrate the accuracy of our registration-based analysis in aligning layer boundaries. By nonlinearly registering the OCT volumes of DR subjects to an atlas constructed from normal controls and measuring the Jacobian determinant of the deformation, we can simultaneously visualize tissue contraction and expansion due to DR pathology. Tensor-based morphometry (TBM) can also be performed for quantitative analysis of local structural changes. In our experimental results, we apply our method to a dataset of 105 subjects and demonstrate that volumetric OCT registration and TBM analysis can successfully detect local retinal structural alterations due to DR.


Analyses of the cellular clock gene expression in peripheral tissue, caudal fin, in the Japanese flounder, Paralichthys olivaceus.
Understanding the systems for maintaining the circadian rhythms that give organisms the flexibility to adapt to environmental changes is important in both aquaculture and fish chronobiology, because nursery lighting conditions can affect the survival and growth rates of larvae. We previously demonstrated that in flounder, the suprachiasmatic nucleus (SCN) exhibits daily rhythm in per2 expression, in sharp contrast to zebrafish, in which the SCN does not exhibit clear per2 expression rhythm. To examine whether a hierarchy exists in systems that maintain the expression rhythm of peripheral clock genes in flounder, in the present study we analyzed the in vivo and in vitro expression of three clock genes, per2, per1, and cry1, in the caudal fin and the effects of cortisol and melatonin administration on the expression of each clock gene. In vivo, the fin maintained a daily expression rhythm of all three genes, even in 24-h darkness (DD) when shifted from 12-h light:12-h dark (LD) conditions, but fin explants lost the expression rhythm after a short time of tissue culture, even under LD conditions. Cortisol, but not melatonin, significantly upregulated the expression of the three clock genes in fin both in vitro and in vivo. Therefore, we hypothesize that the SCN-pituitary-adrenal cortex pathway plays a role in the oscillation of the peripheral clock in flounder. However, in vivo, peak expression of per2 and cry1 was shifted 2-4h earlier under DD conditions, and their expression was upregulated in response to short exposures to light when larvae were kept under DD conditions. Therefore, we also hypothesize that in addition to the SCN, a light-responsive coordinating factor also functions in photo-entrainment of the peripheral clock in flounder.


Detection of IgG in supernatants of pokeweed mitogen-stimulated human lymphocyte cultures by one step solid-phase radioimmunoassay (SPRIA).
A one step solid phase radioimmunoassay is used as a simple and reproducible method of detection and quantitation of IgG produced by human PBL after stimulation with PWM. Modifications of culture conditions are necessary to make culture supernatants suitable for this assay. Pulsing with PWM must be performed in serum-supplemented culture medium for 4-5 days. After thorough washing, medium is then replaced with serum-free medium. Under these conditions, synthesis and secretion of IgG continues for at least 9 days. The amount of IgG produced by 10(6) normal adult PBL as detected in this system is 0.77 +/- 0.47 micrograms. No close correlation between cell proliferation and IgG synthesis was observed.


Z-palatoplasty and tongue radiofrequency for patients with small tonsils.
To explore the feasibility and efficacy of Z-palatoplasty for the management of severe obstructive sleep apnea-hypopnea syndrome in patients with tonsils. Case series and chart review. University hospital. Z-palatoplasty and coblation channeling of the tongue were performed in 36 patients with body mass index <40 kg/m(2) and size 1 or 2 tonsils. All patients' tonsils were preserved. Follow-up continued for at least 1 year. Success was defined as a postoperative apnea-hypopnea index <15 events per hour and at least 50% less than the preoperative value. The surgical success rate was 58.3% (21/36 patients). Furthermore, 66.7% (24/36 patients) had a ≥ 50% reduction in the apnea-hypopnea index to less than 20 episodes per hour. There were statistically significant differences in preoperative nadir oxygen saturation, percentage of time with oxygen saturation less than 90%, microarousal index, and Friedman tongue position between those who responded to surgery and those who did not. Six patients had temporary velopharyngeal insufficiency. After 3 months, all the patients had normal deglutition. No major perioperative complications occurred. Our findings suggest that Z-palatoplasty can improve disease-specific quality of life and sleep apnea symptoms in patients with obstructive sleep apnea-hypopnea syndrome and size 1 or 2 tonsils.


Cascaded optically injection-locked semiconductor laser, rate equations analysis, frequency response, and its application for complex optical signal generation.
In this paper, we introduce the concept of the cascaded optically injection-locked (OIL) semiconductor laser and present its novel rate equations. Then, the new locking range for this configuration has been obtained by mathematical demonstration. Subsequently, we modified a new adjustment for the detuning frequencies (Δ f i n j ) of the cascaded OIL system as well as the linewidth enhancement factors (α) values. Utilizing these tunings, improvements in the steady-state photon number and the phase modulation (PM) range become possible. Afterward, we define the generation of the complex optical signal area and extract the transfer function for investigating the frequency response of the cascaded system. The simulations have been performed once with identical α values and once with the various α values in the slave laser (SL) stages. We conclude that these novel proposed adjustments, combined with a strong injection ratio (Rinj) of 15 dB and a high bias current, can significantly broaden the bandwidth near 700 GHz while maintaining the fair gain available up to 180 GHz. Further, the generation of complex optical signal areas has been boosted for high-quality complex modulation applications. Eventually, we exhibit a novel approach for generating different α values in the SL stages by applying managed temperature variations in the experimental setup of the cascaded system, regardless of employing similar SLs.


Assessing and developing the evidence base of macro practice interventions with a community and neighborhood focus.
Assessing and developing the evidence base of macro practice with a community and neighborhood focus is challenging because of the lack of rigorous studies, difficulties posed by conducting research at the community level, and lack of evaluation capacity at multiple levels of practice. Current evidence on community interventions is summarized. Resources for assessing community interventions are presented, along with strategies for searching, appraising, and synthesizing the evidence. Challenges and potential solutions to developing the evidence base of community interventions are discussed, including defining and analyzing complex community interventions, developing rigorous research designs, and building the evaluation capacity of community-based organizations.


Safety Assessment of Food and Feed from GM Crops in Europe: Evaluating EFSA's Alternative Framework for the Rat 90-day Feeding Study.
Regulatory-compliant rodent subchronic feeding studies are compulsory regardless of a hypothesis to test, according to recent EU legislation for the safety assessment of whole food/feed produced from genetically modified (GM) crops containing a single genetic transformation event (European Union Commission Implementing Regulation No. 503/2013). The Implementing Regulation refers to guidelines set forth by the European Food Safety Authority (EFSA) for the design, conduct, and analysis of rodent subchronic feeding studies. The set of EFSA recommendations was rigorously applied to a 90-day feeding study in Sprague-Dawley rats. After study completion, the appropriateness and applicability of these recommendations were assessed using a battery of statistical analysis approaches including both retrospective and prospective statistical power analyses as well as variance-covariance decomposition. In the interest of animal welfare considerations, alternative experimental designs were investigated and evaluated in the context of informing the health risk assessment of food/feed from GM crops.


[Primary cardiac malignant fibrous histiocytoma in 47-year-old woman].
A case of pleomorphic malignant fibrous histiocytoma of the right atrium and right ventricle is presented. Primary cardiac malignant fibrous histiocytoma (MFH) is extremely rare and its etiology and clinical course are not precisely known. We treated a 47-year-old female patient with persistent fever and cough, shortness of breath and anasarca. The patient died after eight months with symptoms of cardiac shock. Autopsy revealed a big soft yellow tumor in the right heart. Microscopically, atypical fibroblast-like cells, pleomorphic and multinucleated giant tumor cells with eosinophilic cytoplasm were observed within the myxoid and fibrous stroma. Immunohistochemically, tumor cells were positive for alfa-1-antitrypsin and partially positive for CD68 and vimentin. According to histopathologic and immunohistochemical features we diagnosed pleomorphic MFH.


The Shackles of Fear: A Moderated Mediation Model of How Fear of Aging May Increase Older Adults' Vulnerability to Fraud.
Objectives: Older adults are disproportionately vulnerable to frauds of many kinds, and fear of aging has been conjectured to be a primary factor in older adults' vulnerability to fraud; however, no study has examined how and when fear of aging is associated with older adults' vulnerability to fraud.Methods: In this cross-sectional study, a sample of 251 Chinese older adults (M = 68.1, SD = 6.43) completed measures regarding fear of aging, intolerance of uncertainty, self-control, and vulnerability to fraud.Results: The results revealed that intolerance of uncertainty partially mediated the association between fear of aging and vulnerability to fraud. This indirect effect of fear of aging on vulnerability to fraud was only significant for older adults with lower levels of self-control.Conclusions: The association between fear of aging and older adults' vulnerability to fraud through intolerance of uncertainty varies as a function of self-control.Clinical implications: Clinicians may focus on reducing the fear of aging, decreasing intolerance of uncertainty, and enhancing self-control as promising pathways to develop effective interventions and outreach strategies aimed at protecting older adults from fraud.


Research on the applicability of an exercise rehabilitation app aiming to improve the mental and physical health of breast cancer patients in the post-operative period.
Breast cancer is one of the most common malignant cancers in women, seriously endangering the physical and mental health of patients. In this study, we developed an app for breast cancer patients undergoing radiotherapy or chemotherapy with a focus on exercise interventions, supplemented by nutritional and psychological interventions, to verify the applicability of the app for these patients and its impact on their quality of life, sleep, and psychological state. We also investigated the patients' experience and perceptions of the app. A total of 17 participants, aged 42-58 years, were recruited for this study using a mixed-methods design, including quantitative group pre-and post-test scores and qualitative interview results. The participants used the app for 8-18 weeks depending on their radiotherapy or chemotherapy cycle. During the radiotherapy or chemotherapy period, the participants used the "Yun Dong Ru Kang" exercise rehabilitation app to perform aerobic exercises twice a week, as well as rehabilitation exercises appropriate to their radiotherapy or chemotherapy stage, and used the app on their own the rest of the time. The primary results included their scores on the PSSUQ overall assessment usability questionnaire, the users' use of the app, and the results of the interviews; the secondary indicators were quality of life, sleep status, and anxiety and depression status. An overall score of 6.2 (out of 7 points) on the PSSUQ questionnaire indicates the high usability; the average use time per subject per week was 97.69 ± 11.82 min, which exceeds the minimum use time, but the average use time tended to decrease as the use time was postponed. Promoted articles on nutritional diets received the most hits. The results of the interviews were consistent with the questionnaire scores, with the majority of participants believing that the means of exercise should be enriched and the interface optimized, while the reduction in the length of use was related to the participants' own state of learning about calisthenics. In the results of the Breast Cancer-Specific Scale FACT-B, there was a significant increase (p < 0.05) in the Emotional Status dimension score and a significant decrease (p < 0.05) on the Additional Concerns dimension score. In the results of the Pittsburgh Sleep Quality Inventory PSQI, there was a non-significant improvement in all items except for a significant increase (p < 0.05) for the Hypnotic Medication item. In the Hospital Anxiety and Depression Scale (HADS), there was no significant improvement in any of the anxiety and depression factors. The "Yun Dong Ru Kang "app has certain applicability, and the use of the exercise rehabilitation app may effectively reduce the negative impact of chemotherapy side effects on the quality of life, sleep and depression of breast cancer patients in the chemotherapy or radiotherapy phase. Before it is put into use in the future, the app should be enriched with exercise tools, the interface should be optimized, and articles on nutrition and diet should be promoted.


Magnetic microwire probes for the magnetic rod interfacial stress rheometer.
The magnetic needle interfacial shear rheometer is a valuable tool for the study of the mechanical properties of thin fluid films or monolayers. However, it is difficult to differentiate the interfacial and subphase contributions to the drag on the needle. In principle, the problem can be addressed by decreasing the needle diameter, which decreases the bulk contribution while the interfacial contribution remains essentially the same. Here we show the results obtained when using a new type of needle, that of magnetic microwires with diameter approximately 10 times thinner than for commercial needles. We show that the lower inertia of the microwires calls for a new calibration procedure. We propose such a new calibration procedure based on the flow field solution around the needle introduced in refs 1 and 2. By measuring thin silicone oil films with well-controlled interfacial viscosities as well as eicosanol (C20) and pentadecanoic acid (PDA, C15) Langmuir monolayers, we show that the new calibration method works well for standard needles as well as for the microwire probes. Moreover, we show that the analysis of the force terms contributing to the force on the needle helps to ascertain whether the measurements obtained are reliable for given surface shear viscosity values. We also show that the microwire probes have at least a 10-fold-lower resolution limit, allowing one to measure interfacial viscosities as low as 10(-7) N·m/s.


[The concept of protein profile].
From their own experience of the simultaneous immunonephelometry of eight serum proteins, the authors propose a definition of protein profile from the point of view both of laboratory technique and interpretation. The assay should be performed quickly and the results expressed diagrammatically in normalised values, in such a way that the relative variation in protein levels can be easily visualised. A protein profile should thus comprise a minimum of proteins to be measured, chosen according to protein physiopathology and the type of abnormality under investigation. Interpretation is based on inter-protein correlations that may appear or disappear depending on the underlying physiopathology. This makes it possible to study inter-protein variation and thus avoid the probabilistic "interpretation" of single proteins taken in isolation. From this approach syndromes can be divided into two groups, elementary or complex. The authors provide examples of each, and propose an interpretation model based on this dichotomy.


Palladium(II)-catalyzed enantioselective synthesis of α-(trifluoromethyl)arylmethylamines.
Trifluoromethylacetaldimines, generated in situ from the corresponding N,O-acetals, undergo 1,2-addition of arylboroxines under palladium(II) catalysis to generate a variety of α-(trifluoromethyl)arylmethylamines with good to high enantioselectivity (up to 97% ee). The pyridine-oxazolidine (PyOX) class of ligands was found to be particularly suitable for this transformation, which proceeds without exclusion of ambient air and moisture.


CD80 (B7-1) and CD86 (B7-2) are functionally equivalent in the initiation and maintenance of CD4+ T-cell proliferation after activation with suboptimal doses of PHA.
Effective activation of T cells requires engagement of two separate T-cell receptors. The antigen-specific T-cell receptor (TCR) binds foreign peptide antigen-MHC complexes, and the CD28 receptor binds to the B7 (CD80/CD86) costimulatory molecules expressed on the surface of antigen-presenting cells (APC). The simultaneous triggering of these T-cell surface receptors with their specific ligands results in an activation of this cell. In contrast, CTLA-4 (CD152) is a distinct T-cell receptor that, upon binding to B7 molecules, sends an inhibitory signal to T cell activation. Many in vitro and in vivo studies demonstrated that both CD80 and CD86 ligands have an identical role in the activation of T cells. Recently, functions of B7 costimulatory molecules in vivo have been investigated in B7-1 and/or B7-2 knockout mice, and the authors concluded that CD86 could be more important for initiating T-cell responses, while CD80 could be more significant for maintaining these immune responses. In this study, we directly compared the role of CD80 and CD86 in initiating and maintaining proliferation of resting CD4(+) T cells in an in vitro mode system that allowed to provide the first signal-to-effector cells through the use of suboptimal doses of PHA and the second costimulatory signal through cells expressing CD80 or CD86, but not any other costimulatory molecules. Using this experimental system we demonstrate that the CD80 and CD86 molecules can substitute for each other in the initial activation of resting CD4(+) T cells and in the maintenance of their proliferative response.


Putative Silicon Transporters and Effect of Temperature Stresses and Silicon Supplementation on Their Expressions and Tissue Silicon Content in Poinsettia.
Silicon (Si) is a beneficial element for plants. To understand Si uptake and accumulation in poinsettia, the Si transporters and their expression patterns were investigated. Nodulin 26-like intrinsic membrane proteins (NIPs) act as transporters of water and small solutes, including silicic acid. In this study, one NIP member, designated EpLsi1, was identified. Additionally, a protein from the citrate transporter family, designated EpLsi2, was identified. Sequence analyses indicated that EpLsi1 belonged to the NIP-I subgroup, which has a low Si uptake capacity. Consistently, the measured tissue Si content in the poinsettia was less than 1.73 ± 0.17 mg·g-1 dry weight, which was very low when compared to that in high Si accumulators. The expressions of EpLsi1 and EpLsi2 in poinsettia cuttings treated with 0 mg·L-1 Si decreased under temperature stresses. A short-term Si supplementation decreased the expressions of both EpLsi1 and EpLsi2 in the roots and leaves, while a long-term Si supplementation increased the expression of EpLsi1 in the leaves, bracts, and cyathia, and increased the expression of EpLsi2 in the roots and leaves. Tissue Si content increased in the roots of cuttings treated with 75 mg·L-1 Si at both 4 and 40 °C, indicating that the transport activities of the EpLsi1 were enhanced under temperature stresses. A long-term Si supplementation increased the tissue Si content in the roots of poinsettia treated with 75 mg·L-1 Si. Overall, poinsettia was a low Si accumulator, the expressions of Si transporters were down-regulated, and the tissue Si content increased with temperature stresses and Si supplementation. These results may help the breeding and commercial production of poinsettia.


The extrinsic coagulation activity assay.
A chromogenic assay for the tissue factor-mediated thrombin generation was developed, the extrinsic coagulation activity assay: 50 microL citrated plasma is incubated with 5 microL tissue factor in 6% albumin and 250 mM CaCl2. After 1-minute (37 degrees C) coagulation reaction time, (extrinsic coagulation activity assay with 1-minute coagulation reaction time; generating normally about 1 IU/mL thrombin) 100 microL 2.5 M arginine is added to stop hemostasis activation. Generated thrombin is then chromogenically quantified. The normal extrinsic coagulation activity assay range is 100% +/- 20%. Extrinsic coagulation activity assay in plasma of patients on heparin or coumarines is about 10-fold lower. Advantages of extrinsic coagulation activity assay: normal range of extrinsic hemostasis is truly represented, patients prone to hyper-activated extrinsic pathway are detected, anticoagulants result in respective test inhibition, fibrinogen/fibrin concentration does not artefactually alters the test result, plasma matrix is not changed significantly in the assay, and assay results are IU/mL thrombin or % of normal, which can be measured by every normal photometer.


Modelling human skull growth: a validated computational model.
During the first year of life, the brain grows rapidly and the neurocranium increases to about 65% of its adult size. Our understanding of the relationship between the biomechanical forces, especially from the growing brain, the craniofacial soft tissue structures and the individual bone plates of the skull vault is still limited. This basic knowledge could help in the future planning of craniofacial surgical operations. The aim of this study was to develop a validated computational model of skull growth, based on the finite-element (FE) method, to help understand the biomechanics of skull growth. To do this, a two-step validation study was carried out. First, an in vitro physical three-dimensional printed model and an in silico FE model were created from the same micro-CT scan of an infant skull and loaded with forces from the growing brain from zero to two months of age. The results from the in vitro model validated the FE model before it was further developed to expand from 0 to 12 months of age. This second FE model was compared directly with in vivo clinical CT scans of infants without craniofacial conditions (n = 56). The various models were compared in terms of predicted skull width, length and circumference, while the overall shape was quantified using three-dimensional distance plots. Statistical analysis yielded no significant differences between the male skull models. All size measurements from the FE model versus the in vitro physical model were within 5%, with one exception showing a 7.6% difference. The FE model and in vivo data also correlated well, with the largest percentage difference in size being 8.3%. Overall, the FE model results matched well with both the in vitro and in vivo data. With further development and model refinement, this modelling method could be used to assist in preoperative planning of craniofacial surgery procedures and could help to reduce reoperation rates.


Retracted Nonfatal firearm injuries: Utilization and expenditures for children pre- and postinjury.
Firearm injuries are one of the leading preventable causes of morbidity and mortality among children. Limited information exists about the impact of nonfatal firearm injuries on utilization and expenditures. Our objective was to compare health care encounters and expenditures 1 year before and 1 year following a nonfatal firearm injury. This was a retrospective cohort study of children 0 to 18 years with ICD-9/ICD-10 diagnosis codes for firearm injury in the emergency department or inpatient setting from 2010 to 2016 in the Medicaid MarketScan claims database. Outcomes included 1) difference in health care encounters for 1 year before and 1 year after injury, 2) difference in health care expenditures, and 3) difference in complex chronic disease status. Descriptive statistics characterized patient demographics and health care utilization. Health expenditures were evaluated with Wilcoxon signed-rank tests. Among 3,296 children, there were 47,660 health care encounters before the injury and 61,660 after. Concomitantly, there was an overall increase of $18.5 million in health expenditures ($5,612 per patient). There was a 40% increase in children qualifying for complex chronic condition status after firearm injury. Children who experience nonfatal firearm injury have increased number of health care encounters, chronic disease classification, and health care expenditures in the year following the injury. Prevention of firearm injuries in this vulnerable age group may result in considerable reductions in morbidity and health care costs.


Acoustic waveform of continuous bubbling in a non-Newtonian fluid.
We study experimentally the acoustic signal associated with a continuous bubble bursting at the free surface of a non-Newtonian fluid. Due to the fluid rheological properties, the bubble shape is elongated, and, when bursting at the free surface, acts as a resonator. For a given fluid concentration, at constant flow rate, repetitive bubble bursting occurs at the surface. We report a modulation pattern of the acoustic waveform through time. Moreover, we point out the existence of a precursor acoustic signal, recorded on the microphone array, previous to each bursting. The time delay between this precursor and the bursting signal is well correlated with the bursting signal frequency content. Their joint modulation through time is driven by the fluid rheology, which strongly depends on the presence of small satellite bubbles trapped in the fluid due to the yield stress.


Compact and broadband data exchange for mode-division-multiplexed networks.
Recently, mode-division multiplexing (MDM) technology has been used to enable high-bandwidth data transmission. Information swapping or data exchange is an essential function in such high-capacity networks. This paper presents a small, broadband on-chip optical data exchange between two multiplexed modes on the silicon-on-insulator platform. The device consists of a three-waveguide coupler in which the middle waveguide has a hybrid plasmonic structure and the two other ones are silicon waveguides. The total length and the width of the proposed structure are 15.25 μm and 1.0885 μm, respectively. The 3D finite-difference-time-domain simulation results show that the insertion loss is less than 2 dB for a broad bandwidth of 100 nm, over which the crosstalk is lower than -14.7 dB and -21.9 dB for TM0 to TM1 and TM1 to TM0 conversion, respectively.


The control of globin and other eukaryotic genes.
The hypothesis is advanced that eukaryotes control different parts of their genomes by the selective use of origins of replication. Replication of a gene from an origin upstream of the gene is postulated to open it for transcription under appropriate circumstances; replication of a gene from an origin downstream of the gene closes it. The applicability of this hypothesis to the control of the human beta-globin cluster of genes is considered.


Micro-TESE surgery combined with ICSI regimen in the treatment of non-obstructive azoospermia patients and its effect analysis.
This study aimed to analyze the clinical effects of microdissection testicular sperm extraction (micro-TESE) surgery combined with an intracytoplasmic sperm injection (ICSI) regimen in the treatment of non-obstructive azoospermia (NOA) patients with different etiologies. In total, 128 NOA patients participated in this study, in which they received infertility treatment by micro-TESE surgery combined with an ICSI regimen, and all patients were divided into three groups [the Klinefelter syndrome (KS), the idiopathic and the secondary NOA groups]. In addition, the sperm retrieval rate (SRR), fertilization rate, embryo development status and clinical treatment effects were analyzed. Among the 128 NOA patients, the SRR of KS NOA patients was 48.65%, those of idiopathic and the secondary patients were 33.82% and 73.91%, respectively. Regardless of etiologies, there was no correlation with age, hormone value or testicular volume. Further analysis showed that the SRR of the KS group was positively related with testosterone (T) values, and the SRR of the secondary group had a positive relationship with follicle-stimulating hormone or luteinizing hormone values. In the subsequent clinical treatment, the retrieved sperm was subjected to ICSI and achieved good treatment effects, especially in the secondary group, and the implantation rate (55.56%) and clinical pregnancy rate (68.42%) were both higher than those of the idiopathic group (28.75% and 40.00%) and KS group (22.05% and 30.77%). Micro-TESE surgery combined with ICSI insemination is the most effective treatment regimen for NOA patients. The SRR of NOA patients with different etiologies are related to certain specific factors, and micro-TESE surgery seems to be the ideal and only way to have biological children.


When to Pick the Nose: Out-of-Hospital and Emergency Department Intranasal Administration of Medications.
The intranasal route for medication administration is increasingly popular in the emergency department and out-of-hospital setting because such administration is simple and fast, and can be used for patients without intravenous access and in situations in which obtaining an intravenous line is difficult or time intensive (eg, for patients who are seizing or combative). Several small studies (mostly pediatric) have shown midazolam to be effective for procedural sedation, anxiolysis, and seizures. Intranasal fentanyl demonstrates both safety and efficacy for the management of acute pain. The intranasal route appears to be an effective alternative for naloxone in opioid overdose. The literature is less clear on roles for intranasal ketamine and dexmedetomidine.


Aflatoxin B1 binding to sorbents in bovine ruminal fluid.
A recent approach to the problem of contamination of agricultural products by aflatoxin B(1) (AFB(1)) is to add non-nutritional adsorbents to animal diets in order to sequester ingested aflatoxins. We conducted in vitro experiments to develop a rapid and cheap model using ruminal fluid to assess the ability of sorbent materials to bind AFB(1). Seven sorbents (hydrated sodium calcium aluminosilicate; clinoptilolite; zeolite; two types of bentonite; sepiolite; and PHIL 75), commonly added to bovine diets were incubated in water and ruminal fluid in the presence of AFB(1). Hydrated sodium calcium aluminosilicate, sepiolite and one of the bentonites bound 100% of the AFB(1) in the presence of both ruminal fluid and water; clinoptilolite bound about 80% of AFB(1) in both liquids; whereas the affinities for the mycotoxin of zeolite (50%) and the other sample of bentonite (60%) in water seem to be increased by about 40% in ruminal fluid incubations. PHIL 75 had the poorest binding ability: about 30% in water and 45% in ruminal fluid. In view of the differences in toxin binding in water and ruminal fluid, it is preferable to use the ruminal fluid model for the in vitro pre-screening of sorbent materials potentially useful as adjuvants to ruminant feeds.


Orthodontic treatment need of mentally handicapped children in Ibadan, Nigeria, according to the dental aesthetic index.
Proper well-organized orthodontic treatment planning for special needs patients quantifies such needs with a valid screening method to determine priority treatment. The aim of this study was to determine the orthodontic treatment needs of mentally handicapped children in Ibadan, Nigeria. The sample consisted of 124 mentally handicapped children, 68 boys and 56 girls who were 6 to 18 years old with mean age of 14.5 +/- 1.5 years, drawn from 7 special centers/schools in the city. Less than 42% had normal or minor malocclusions needing slight or no treatment; 17% had definite malocclusions with treatment elective; 9% had severe malocclusions and treatment highly desirable; 32% had very severe or handicapping malocclusions with treatment considered mandatory. Significant gender differences were found in the mean dental aesthetic index (DAI) scores (P < .05) and significant association noted (P < .05) between severe mental retardation and DAI scores deserving treatment. There were considerable orthodontic treatment needs among the study population with a reasonable percentage deserving treatment in publicly funded programs.


Intrathecal chemotherapy for hematologic malignancies: drugs and toxicities.
Intrathecal (IT) chemotherapy is an important component of the prophylaxis or treatment of hematologic malignancies in the central nervous system (CNS), especially in patients with acute lymphoblastic leukemia and aggressive lymphomas. Different regimens of IT chemotherapies have been formulated, often in conjunction with systemic high-dose chemotherapy leading to penetration of the drugs into the cerebrospinal fluid (CSF). The three commonest IT drugs are methotrexate, cytosine arabinoside (Ara-C), and corticosteroids. The CSF half-lives of methotrexate and Ara-C are much prolonged, a factor to be considered if these drugs are also administered systemically in high doses. Neurotoxicities attributed to IT chemotherapy have been reported, including spinal cord lesions, seizures, and encephalopathy. Spinal cord lesions, manifesting as tetraplegia, paraplegia, and cauda equina syndrome, are the commonest neurotoxicity. It is mostly related to combined IT methotrexate and Ara-C, or Ara-C as the sole IT agent when given at high doses or as a slow-release preparation. Cord lesions rarely recover and patients are left with motor deficits, bowel and urinary disabilities. Seizures and encephalopathy are reported in relatively fewer patients, with variable manifestations and prognosis. Knowledge of the pharmacokinetics, dosing schedules and potential toxicities of IT chemotherapeutic drugs is important in the design of CNS prophylaxis and treatment in hematologic malignancies.


Activation of early gene expression in T lymphocytes by Oct-1 and an inducible protein, OAP40.
After antigenic stimulation of T lymphocytes, genes essential for proliferation and immune function, such as the interleukin-2 (IL-2) gene, are transcriptionally activated. In both transient transfections and T lymphocyte-specific in vitro transcription, the homeodomain-containing protein Oct-1 participated in the inducible regulation of transcription of the IL-2 gene. Oct-1 functioned in this context with a 40-kilodalton protein called Oct-1-associated protein (OAP40). In addition to interacting specifically with DNA, OAP40 reduced the rate of dissociation of Oct-1 from its cognate DNA-binding site, suggesting that a direct interaction exists between Oct-1 and OAP40.


Preconditioning provides neuroprotection in models of CNS disease: paradigms and clinical significance.
Preconditioning is a phenomenon in which brief episodes of a sublethal insult induce robust protection against subsequent lethal injuries. Preconditioning has been observed in multiple organisms and can occur in the brain as well as other tissues. Extensive animal studies suggest that the brain can be preconditioned to resist acute injuries, such as ischemic stroke, neonatal hypoxia/ischemia, surgical brain injury, trauma, and agents that are used in models of neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. Effective preconditioning stimuli are numerous and diverse, ranging from transient ischemia, hypoxia, hyperbaric oxygen, hypothermia and hyperthermia, to exposure to neurotoxins and pharmacological agents. The phenomenon of "cross-tolerance," in which a sublethal stress protects against a different type of injury, suggests that different preconditioning stimuli may confer protection against a wide range of injuries. Research conducted over the past few decades indicates that brain preconditioning is complex, involving multiple effectors such as metabolic inhibition, activation of extra- and intracellular defense mechanisms, a shift in the neuronal excitatory/inhibitory balance, and reduction in inflammatory sequelae. An improved understanding of brain preconditioning should help us identify innovative therapeutic strategies that prevent or at least reduce neuronal damage in susceptible patients. In this review, we focus on the experimental evidence of preconditioning in the brain and systematically survey the models used to develop paradigms for neuroprotection, and then discuss the clinical potential of brain preconditioning.


Construction of COD simulation model for activated sludge process by fuzzy neural network.
Fuzzy neural network (FNN) was applied to construct a simulation model for estimating the effluent chemical oxygen demand (COD) value of an activated sludge process in a "U" plant, in which most of process variables were measured once an hour. The constructed FNN model could simulate periodic changes in COD with high accuracy. Comparing the simulation result obtained using the FNN model with that obtained using the multiple regression analysis (MRA) model, it was found that the FNN model had 3.7 times higher accuracy than the MRA model. The FNN models corresponding to each of the four seasons were also constructed. Analyzing the fuzzy rules acquired from the FNN models after learning, the operational characteristic of this plant could be elucidated. Construction of the simulation model for another plant "A", in which process variables were measured once a day, was also carried out. This FNN model also had a relatively high accuracy.


Composite Resin Dosimeters: A New Concept and Design for a Fibrous Color Dosimeter.
Polystyrene (PS)-based composite microfibers combined with a photochromic spiropyran dye, 1,3,3-trimethylindolino-6'-nitrobenzopyrylospiran (6-nitro BIPS), and a photostimulable phosphor, europium-doped barium fluorochloride (BaFCl:Eu2+), were developed for the detection of X-ray exposure doses on the order of approximately 1 Gy. To produce the PS-based composite microfibers, we employed a forcespinning method that embeds a high concentration of phosphor in PS in a safe, inexpensive, and simple procedure. On the basis of the optimization of the forcespinning process, fibrous color dosimeters with a high radiation dose sensitivity of 1.2-4.4 Gy were fabricated. The color of the dosimeters was found to transition from white to blue in response to X-ray exposure. The optimized fibrous color dosimeter, made from a solution having a PS/6-nitro BIPS/BaFCl:Eu2+/C2Cl4 ratio of 7.0/0.21/28.0/28.0 (wt %) and produced with a 290 mm distance between the needle and collectors, a 0.34 mm 23 G needle nozzle, and a spinneret rotational rate of 3000 rpm, exhibited sensitivity to a dose as low as 1.2 Gy. To realize practical applications, we manufactured the optimized fibrous color dosimeter into a clothlike color dosimeter. The clothlike color dosimeter was mounted on a stuffed bear, and its coloring behavior was demonstrated upon X-ray exposure. After exposure with X-ray, a blue colored and shaped in the form of the letter "[Formula: see text]" clearly appeared on the surface of the clothlike color dosimeter. The proposed fibrous color dosimeters having excellent workability will be an unprecedented dosimetry and contributed to all industries utilizing radiation dosimeters. This new fibrous "composite resin dosimeter" should be able to replace traditional, wearable, and individual radiation dose monitoring devices, such as film badges.


Huge pancreatic acinar cell carcinoma with high levels of AFP and fucosylated AFP (AFP-L3).
A 25-year-old Japanese woman with a large abdominal tumor (10 cm in diameter) and high level of serum alpha-fetoprotein (AFP, 1,222.4 ng/mL) was introduced and admitted to our hospital in January 2011. Pre-operative imaging modalities could not identify the tumor origin. There was no chronic hepatic viral disease, however, the elevated level of fucosylated AFP (87.8%) and connection with the left hepatic lobe led us to diagnose the tumor as a hepatocellular carcinoma. Surgical resection was performed in February. Histological findings revealed a pancreatic acinar cell carcinoma (ACC). Herein, we provide details of this difficulty to diagnose a case of ACC.


High Serum AST/ALT Ratio and Low Serum INS*PA Product Are Risk Factors and Can Diagnose Sarcopenia in Middle-Aged and Older Adults.
Sarcopenia is an age-related clinical condition and associated with an increased risk of adverse outcomes. However, to date, there is no global standard for the diagnosis of sarcopenia, and fewer serum biomarkers have been suggested for the diagnosis of sarcopenia. It is, thus, important that sarcopenia-related serological diagnostic markers be explored. The present study was based on the Asian Working Group on Sarcopenia 2019 (AWGS 2019) criteria to assess whether aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio and fasting insulin*prealbumin (INS*PA) product are diagnostic markers associated with sarcopenia in various ethnic groups in western China. This cross-sectional study included 4,099 adults (1,471 men and 2,628 women) from the West China Health and Aging Trend (WCHAT) study. The value of serum biomarkers was based on laboratory data. The accompanying metabolic disorders and the associated parameters were evaluated. Logistic regression analysis was used to explore the association between markers and sarcopenia. Receiver operating characteristic curve (ROC) analysis was used to evaluate the diagnostic efficacy of the test in differentiating sarcopenia. Binary regression analysis showed that high serum AST/ALT (OR = 2.247) and adrenal cortisol (PTC, OR = 1.511), low serum INS*PA (OR = 2.970), free triiodothyronine (FT3, OR = 1.313), 25-OH-VitD (VitD, in male participants, OR = 1.817), and diastolic blood pressure (DBP, in female subjects, OR = 1.250) were independent risk factors for sarcopenia (P < 0.05). AST/ALT and INS*PA were not affected by metabolic factors and had better diagnostic efficacy for sarcopenia. The AUC of the INS*PA was the highest (0.705, 0.706, and 0.701, respectively, P < 0.05), followed by that of the AST/ALT (0.680, 0.675, and 0.695, respectively, P < 0.05). The AUC of the AST/ALT/(INS*PA)*10,000 used to diagnose sarcopenia was 0.727. Among middle-aged and older adults of multiple ethnicities in western China, we found that higher AST/ALT and lower INS*PA levels are associated with an increased prevalence of sarcopenia. Since these serum biomarkers are inexpensive and can be obtained easily from biochemical routine, regular follow-up of AST/ALT and INS*PA may be an effective strategy in sarcopenia screening and management.


Association Between the Mental Health of Patients With Psoriasis and Their Satisfaction With Physicians.
How patients' mental health is associated with their satisfaction with physicians is rarely studied among adults with skin conditions. To examine the association between mental health comorbidities in patients with psoriasis and their satisfaction with physicians. This retrospective survey analysis used 14 years of nationally representative longitudinal data on adults in the United States with psoriasis from the 2004-2017 Medical Expenditure Panel Survey. Statistical analysis was performed from October 1, 2018, to December 1, 2019. Mental health comorbidities were measured by performance on the Kessler 6-Item Psychological Distress Scale (score range, 0-24, where a score ≥13 is considered an indicator of a serious mental illness and significant psychological distress) and the Patient Health Questionnaire 2 (score range, 0-6, where a score ≥3 is considered a positive screening result for a depressive disorder). Patient satisfaction with physician, measured by the patient-physician communication composite score. A weighted total of 8 876 767 US adults with psoriasis (unweighted total, 652 patients) (weighted; 54% women; mean [SEM] age, 52.1 [0.7] years) were analyzed; 27% of adults had moderate or severe symptoms of psychological distress, and 21% had moderate or severe symptoms of depression. Patients with moderate or severe psychological distress symptoms were less satisfied with their clinicians compared with those with no or mild psychological distress symptoms (mean Kessler 6-Item Psychological Distress Scale scores for no or mild symptoms, 14.3 [95% CI, 14.2-14.4]; moderate symptoms, 13.2 [95% CI, 13.0-13.4]; and severe symptoms, 13.1 [95% CI, 12.5-13.7]; P < .001). In addition, compared with patients with no or mild psychological distress symptoms, patients with moderate psychological distress symptoms were 2.8 times more likely to report low patient satisfaction (adjusted odds ratio, 2.8 [95% CI, 1.5-4.9]; P = .001), and patients with severe psychological distress symptoms were 2.3 times more likely to report low patient satisfaction (adjusted odds ratio, 2.3 [95% CI, 1.1-4.7]; P = .03). Furthermore, patients with moderate or severe depression symptoms were less satisfied with their clinicians compared with those with no or mild depression symptoms (mean Patient Health Questionnaire 2 scores for no or mild symptoms, 14.3 [95% CI, 14.2-14.4]; moderate symptoms, 13.2 [95% CI, 12.9-13.6]; and severe symptoms, 13.0 [95% CI, 12.6-13.4]; P = .002). In addition, compared with patients with no or mild depression symptoms, patients with moderate depression symptoms were 4.6 times more likely to report low patient satisfaction (adjusted odds ratio, 4.6 [95% CI, 2.1-10.0]; P < .001). This study suggests that patients with greater psychological distress and depression report lower satisfaction with their clinicians than those without such mental health symptoms. Clinicians need to be adaptable and supportive when communicating with patients with mental health comorbidities. Evaluating clinician performance solely based on patient satisfaction can be problematic and incomplete.


Liver Resection versus Radiofrequency Ablation plus Transcatheter Arterial Chemoembolization in Cirrhotic Patients with Solitary Large Hepatocellular Carcinoma.
To compare liver resection (LR) with single-step, balloon-occluded radiofrequency (RF) ablation plus drug-eluting embolics transarterial chemoembolization in cirrhotic patients with single hepatocellular carcinoma (HCC) ≥ 3 cm. From 2010 to 2014, 25 patients with compensated cirrhosis and single HCC ≥ 3 cm (median size 4.5 cm; range, 3.0-6.8 cm) not suitable for LR or liver transplantation were treated with RF ablation plus transarterial chemoembolization in a prospective observational single-center pilot study; all patients had complete tumor necrosis after treatment. A retrospective control group included 29 patients (median HCC size 4.0 cm; range, 3.0-7.4 cm) who underwent LR. RF ablation plus transarterial chemoembolization group included more patients with severe portal hypertension (65.5% vs 35.0%, P = .017). Primary endpoints were overall survival (OS) and tumor recurrence (TR) rates. One death and 1 major complication (4%) were observed in LR group. No major complications were reported in RF ablation plus transarterial chemoembolization group (P = .463). OS rates at 1 and 3 years were 91.8% and 79.3% in LR group and 89.4% and 48.2% in RF ablation plus transarterial chemoembolization group (P = 0.117). TR rates at 1 and 3 years were 29.5% and 45.0% in LR group and 42.4% and 76.0% in RF ablation plus transarterial chemoembolization group (P = .034). Local tumor progression (LTP) rates at 3 years were significantly lower in LR group (21.8% vs 58.1%, P = .005). Similar results were found in patients with HCC ≤ 5 cm (TR rates 35.4% vs 75.1%, P = .016; LTP 16.0% vs 55.7%, P = .013). LR achieved lower TR and LTP rates than RF ablation plus transarterial chemoembolization, but 3-years OS rates were not statistically different between the 2 groups. RF ablation plus transarterial chemoembolization is an effective treatment option in patients with compensated cirrhosis and solitary HCC ≥ 3 cm unsuitable for LR.


Construction and initial characterization of a luminescent Synechococcus sp. PCC 7942 Fe-dependent bioreporter.
A Synechococcus sp. PCC 7942 bioreporter strain capable of sensing bioavailable Fe was constructed by fusing the Fe-responsive isiAB promoter to the Vibrio harveyi luxAB genes. Monitoring luxAB-dependent luminescence through the growth curve demonstrated that in Fe-replete media, transcription from the isiAB promoter was induced transiently in the mid-exponential phase of growth. The initiation of transcription was the functional response to a 10-fold depletion of intracellular Fe to approximately 12 amol Fe per cell. Constitutive isiAB-dependent transcription was observed in Fe-depleted growth media. A dose-response relationship of the bioreporter was generated using trace metal-buffered Fraquil medium and was best represented by a sigmoidal curve having a linear component extending between pFe 21.1 (Fe3+=10(-21.1) M) and pFe 20.6 (Fe3+)=10(-20.6) M). Initial field trials conducted using water sampled from Lake Erie demonstrate that the bioreporter can serve as a quantitative tool to assess Fe deficiency in natural freshwater environments.


Enhanced secretion and uptake of beta-glucuronidase improves adeno-associated viral-mediated gene therapy of mucopolysaccharidosis type VII mice.
Previous treatment of mucopolysaccharidosis type VII mice (Sly syndrome) with AAV vectors has resulted in increased levels of beta-glucuronidase (GUS) enzyme in some tissues with reduction of glycosaminoglycan storage granules and improved health. By adding coding sequences for secretion (Igkappa) and uptake (HIV-1 TAT) signals to the GUS gene delivered by AAV, and treating mice both intrathecally and intravenously as newborns, we have increased the GUS enzyme levels in more tissues and have improved the health of the mice so much that they are able to breed. The levels of GUS in the serum were above normal in some mice, which caused reduction of storage in the spleen, a nontransduced tissue. The heart and aorta showed therapeutic levels of GUS enzyme. AAV GUS DNA was found in brain and liver, which showed no storage. Phenotypically the treated mice were more active and showed less stunted skeletal growth. The pups born to these mice were not affected by the gene therapy, as shown by mutant levels of GUS enzyme in their tissues and the absence of AAV GUS DNA. However, they were resistant to intravenous treatment with AAV GUS due to the mother's antibodies, but not to intrathecal treatment.


Targeting glutamine metabolism and the focal adhesion kinase additively inhibits the mammalian target of the rapamycin pathway in spheroid cancer stem-like properties of ovarian clear cell carcinoma in vitro.
Ovarian cancer is one of the leading causes of death in the world, which is linked to its resistance to chemotherapy. Strategies to overcome chemoresistance have been keenly investigated. Culturing cancer cells in suspension, which results in formation of spheroids, is a more accurate reflection of clinical cancer behavior in vitro than conventional adherent cultures. By performing RNA-seq analysis, we found that the focal adhesion pathway was essential in spheroids. The phosphorylation of focal adhesion kinase (FAK) was increased in spheroids compared to adherent cells, and inhibition of FAK in spheroids resulted in inhibition of the downstream mammalian target of the rapamycin (mTOR) pathway in ovarian clear cell carcinomas. This result also suggested that only using a FAK inhibitor might have limitations because the phosphorylation level of FAK could not be reduced to the level in adherent cells, and it appeared that some combination therapies might be necessary. We previously reported that glutamine and glutamate concentrations were higher in spheroids than adherent cells, and we investigated a synergistic effect targeting glutamine metabolism with FAK inhibition on the mTOR pathway. The combination of AOA, a pan-transaminase inhibitor, and PF 573228, a FAK inhibitor, additively inhibited the mTOR pathway in spheroids from ovarian clear cell carcinomas. Our in vitro study proposed a rationale for the positive and negative effects of using FAK inhibitors in ovarian clear cell carcinomas and suggested that targeting glutamine metabolism could overcome the limitation of FAK inhibitors by additively inhibiting the mTOR pathway.


Berberine derivatives as inhibitors of acetylcholinesterase: A systematic review.
Alzheimer's disease (AD) is a chronic age-related neurodegenerative brain disorder characterized by the impairment of memory accompanied by worsening of thinking ability of an individual. The exact pathophysiology of AD is not fully understood. However low level of the neurotransmitter named acetylcholine (ACh), aggregation of Aβ peptide into toxic Aβ plaque, hyperphosphorylation of tau, bio-metal imbalance, and oxidative stress are the main hallmarks of this disease. Due to the complex pathophysiology of AD, no specific treatment is available in the market, and treatment is only limited to the symptomatic relief. So, there is an urgent need for the development of new drug candidate, which can have disease-modifying effect and improve learning and memory in AD patient. Therefore, berberine-based multifunction compounds with potential cholinesterase inhibitory properties were reviewed in this article. Structure-activity relationship (SAR) and biological activity provide highlights on the new derivatives used for the management of AD.


Calculating critical loads for acidification for five forested catchments in China using an extended steady state function.
The critical load concept has become widely accepted as an important theoretical basis for establishing effective acid deposition control strategies. In the critical load calculations, the influence of variation in base cation (BC) deposition, which plays an important role in mitigating acidification, was seldom considered. In this manner, high uncertainty and over-estimation might be caused in those areas where current BC deposition is very high and of significant anthropogenic origin since anthropogenic deposition can change due to human activity. In this study, an extended sulfur(S)-nitrogen (N)-BC function based on the Steady State Mass Balance (SSMB) method is applied to calculate the critical loads for five sampled catchments in southern China under variable S, N, and BC deposition. The ceiling of S deposition (when N deposition is zero; CL(max)(S)) under current BC deposition varies from 4.5 to 10.8 keq ha(-1) yr(-1) among the five catchments, and the ceiling of N deposition (when S deposition is zero; CL(max)(N)) varies from 23.2 to 54.5 keq ha(-1) yr(-1). A 75% reduction in BC deposition is estimated to cause a 46%-86% decrease of CL(max)(S) and 45%-81% decrease of CL(max)(N). The critical loads for acidification are not exceeded in any of the five catchments under the current base cation deposition, despite extremely high S deposition in some places. However, if the BC deposition decreases to 25% of current while S remains unchanged, critical loads will be exceeded at all sites except one. A sensitivity analysis confirms that the long-term future BC deposition is among the most important parameters to the uncertainty of critical load, together with the dose-response relationship between ecosystem health and soil solution chemistry.


Effect of Leg Dominance on The Center-of-Mass Kinematics During an Inside-of-the-Foot Kick in Amateur Soccer Players.
Soccer kicking kinematics has received wide interest in literature. However, while the instep-kick has been broadly studied, only few researchers investigated the inside-of-the-foot kick, which is one of the most frequently performed techniques during games. In particular, little knowledge is available about differences in kinematics when kicking with the preferred and non-preferred leg. A motion analysis system recorded the three-dimensional coordinates of reflective markers placed upon the body of nine amateur soccer players (23.0 ± 2.1 years, BMI 22.2 ± 2.6 kg/m2), who performed 30 pass-kicks each, 15 with the preferred and 15 with the non-preferred leg. We investigated skill kinematics while maintaining a perspective on the complete picture of movement, looking for laterality related differences. The main focus was laid on: anatomical angles, contribution of upper limbs in kick biomechanics, kinematics of the body Center of Mass (CoM), which describes the whole body movement and is related to balance and stability. When kicking with the preferred leg, CoM displacement during the ground-support phase was 13% higher (p<0.001), normalized CoM height was 1.3% lower (p<0.001) and CoM velocity 10% higher (p<0.01); foot and shank velocities were about 5% higher (p<0.01); arms were more abducted (p<0.01); shoulders were rotated more towards the target (p<0.01, 6° mean orientation difference). We concluded that differences in motor control between preferred and non-preferred leg kicks exist, particularly in the movement velocity and upper body kinematics. Coaches can use these results to provide effective instructions to players in the learning process, moving their focus on kicking speed and upper body behavior.


Socioeconomic status and chronic kidney disease at presentation to a renal service in the United Kingdom.
Low socioeconomic status (SES) is associated with both development and progression of chronic kidney disease (CKD). The impact of SES on severity of CKD at presentation to a renal service is less well known. This study investigated the relationship between SES and severity of CKD in a retrospective, cross-sectional analysis involving 1657 patients at the Sheffield Kidney Institute (Sheffield, UK). SES was assigned to each patient according to electoral ward of residence by postcode and ranked according to the corresponding British Index of Multiple Deprivation score, which comprises five deprivation quintiles (Q1, least deprived; Q5, most deprived). National Kidney Foundation Kidney Disease Outcomes Quality Initiative classification of CKD was used for stratification and analysis. Binary logistic regression analysis was applied for the association of variables/risk factors with CKD (lower GFR) at presentation. The age-adjusted prevalence of diagnosed CKD at presentation by area of residence, across the five deprivation quintiles, per million population was Q1 = 1495, Q2 = 3530, Q3 = 3398, Q4 = 3989, and Q5 = 19,599. Logistic regression models showed that living in the lowest SES quintile area (Q5) as compared with the highest SES (Q1) was associated with a greater risk for presenting with a lower estimated GFR, after adjustment for sociodemographic, lifestyle, and clinical variables. Low SES is related to severity of CKD at presentation. Further studies are needed to examine this issue across the various SES categories in the United Kingdom.


Identification of alternative splicing and RNA-binding proteins involved in myocardial ischemia-reperfusion injury.
Alternative splicing (AS) and RNA-binding proteins (RBPs) have been implicated in various cardiovascular diseases. Yet, a comprehensive understanding of their role in myocardial ischemia-reperfusion injury (MIRI) remains elusive. We aimed to identify potential therapeutic targets for MIRI by studying genome-wide changes in AS events and RBPs. We analyzed RNA-seq data from ischemia-reperfusion mouse models and the control group from the GSE130217 data set using Splicing Site Usage Variation Analysis software. We identified 28 regulated alternative splicing events (RASEs) and 47 differentially expressed RBP (DE-RBP) genes in MIRI. Most variable splicing events were involved in cassette exon, alternative 5' splice, alternative 3' splice, and retained intron types. Gene Ontology and Kyoto Encyclopedia of Genes (KOBAS 2.0 server) and Genomes pathway enrichment analyses showed that the differentially expressed variable splicing and RBP genes were mainly enriched in pathways related to myocardial function. The RBP-RASE network demonstrated a common variance relationship between DE-RBPs and RASEs, indicating that RBPs regulate variable shear events in MIRI. This study systematically identified important alterations in RASEs and RBPs in MIRI, expanding our understanding of the underlying pathogenesis of MIRI.


EVOLUTION OF GREGARIOUSNESS IN APOSEMATIC BUTTERFLY LARVAE: A PHYLOGENETIC ANALYSIS.
Gregariousness ought to be disadvantageous for palatable organisms that live exposed and are relatively immobile and small in comparison to potential predators. Therefore, the idea that unpalatability generally evolves before egg clustering/larval gregariousness in butterflies was tested. Aposematic coloration in the larva was used as the criterion of unpalatability (it is argued that Batesian mimicry is rare in butterfly larvae), and the relative order of evolution of aposematism and gregariousness was inferred through phylogenetic analysis. Here, existing phylogenies were used, and the analysis was based on an assumption of a minimum number of evolutionary changes (parsimony). A total of 23 cases of independent evolution of gregariousness and 12 cases of independent evolution of aposematic coloration were found. In five cases, gregariousness evolved in cryptic species, the palatability of which is unknown. For lineages in which both unpalatability, as evidenced by aposematic coloration, and gregariousness were found and the two evolutionary events could be separated, unpalatability always preceded gregariousness: five cases of independent evolution of warning coloration were followed by a total of 15 cases of independent evolution of gregariousness. In no lineage did gregariousness evolve before warning coloration. It is thus concluded that unpalatability is an important predisposing factor for the evolution of egg clustering and larval gregariousness in butterflies. Insofar as kin selection is related to larval gregariousness, this study indicates that kin selection is of minor importance for the evolution of both unpalatability and warning coloration.


Bot fly larvae (Cephenemyia jellisoni) as a cause of neurologic signs in an elk.
In June 1993, a yearling female elk (Cervus elaphus) near John Day, Oregon (USA) was observed twice over a four week period with signs of neurologic disease including weakness, walking in circles with an uncoordinated gait and disorientation. The elk was shot, and the head and neck were examined grossly for parasites and lesions. Thirty-five second and third instar larvae of Cephenemyia jellisoni were recovered from an encapsulated space in the nasopharyngeal area dorsal to the soft palate. Larvae protruded into the caudodorsal end of the ventral nasal meatus, obliterating the opening of the left eustachian tube. Larvae were not recovered from their normal location in the retropharyngeal recesses. Thus the effects of several Cephenemyia jellisoni larvae in an aberrant location mimicked signs observed in meningeal worm infections.


[Cardiogenic Shock Complicating Myocardial Infarction].
In patients admitted with acute myocardial infarction, cardiogenic shock remains the most common cause of death. Multidisciplinary care in a specialized center and guideline-compliant treatment of cardiogenic shock are crucial for the survival and prognosis of affected patients. Hemodynamic monitoring and stabilization by volume expansion, vasopressors and inotropes represent initial steps in the management of patients with cardiogenic shock. Nevertheless, early revascularization of the culprit-lesion is proved to be the most important treatment modality. Although the use of active mechanical circulatory support appears to be a promising therapeutic concept to improve clinical outcome in patients with infarct-related cardiogenic shock, in the few previous randomized trials mechanical circulatory support failed to show beneficial effects on short-term and long-term survival.


Green Ether Electrolytes for Sustainable High-voltage Potassium Ion Batteries.
Ether-based electrolytes are promising for secondary batteries due to their good compatibility with alkali metal anodes and high ionic conductivity. However, they suffer from poor oxidative stability and high toxicity, leading to severe electrolyte decomposition at high voltage and biosafety/environmental concerns when electrolyte leakage occurs. Here, we report a green ether solvent through a rational design of carbon-chain regulation to elicit steric hindrance, such a structure significantly reducing the solvent's biotoxicity and tuning the solvation structure of electrolytes. Notably, our solvent design is versatile, and an anion-dominated solvation structure is favored, facilitating a stable interphase formation on both the anode and cathode in potassium-ion batteries. Remarkably, the green ether-based electrolyte demonstrates excellent compatibility with K metal and graphite anode and a 4.2 V high-voltage cathode (200 cycles with average Coulombic efficiency of 99.64 %). This work points to a promising path toward the molecular design of green ether-based electrolytes for practical high-voltage potassium-ion batteries and other rechargeable batteries.


Selection of an erythromycin for the treatment of pertussis.
Pertussis is one of the most communicable diseases of the respiratory tract and the incidence of this disease has increased substantially in recent years. Bordetella pertussis is the major pathogen implicated and erythromycin is considered the drug of choice. Because more studies have reported bacteriological and clinical relapses with ethylsuccinate and stearate formulations than with the estolate preparation, erythromycin estolate 50 mg/kg/d in divided doses over a 14-day period is recommended for the treatment of pertussis. None of the studies, however, have directly compared various forms of erythromycin in these patients to establish superiority of one form over the others. Treatment should be initiated as soon as possible and patients should be followed closely to achieve maximal efficacy and minimize the spread of the disease.


Inhibition of human DNA polymerase beta activity by the anticancer prodrug Cloretazine.
The antineoplastic prodrug Cloretazine exerts its cytotoxicity via a synergism between 2-chloroethylating and carbamoylating activities that are cogenerated upon activation in situ. Cloretazine is reported here to inhibit the nucleotidyl-transferase activity of purified human DNA polymerase beta (Pol beta), a principal enzyme of DNA base excision repair (BER). The 2-chloroethylating activity of Cloretazine alkylates DNA at the O(6) position of guanine bases resulting in 2-chloroethoxyguanine monoadducts, which further react to form cytotoxic interstrand DNA crosslinks. Alkylated DNA is often repaired via BER in vivo. Inhibition of the polymerase activity of Pol beta may account for some of the synergism between Cloretazine's two reactive subspecies in cytotoxicity assays. This inhibition was only observed using agents with carbamoylating activity. Furthermore, while therapeutically relevant concentrations of Cloretazine inhibited the polymerase activity of Pol beta, the enzyme's lyase activity, which may also participate in BER, was not significantly inhibited.


Interleukin-10 haplotype associated with increased mortality in critically ill patients with sepsis from pneumonia but not in patients with extrapulmonary sepsis.
To test the hypothesis that haplotypes of the interleukin (IL)-10 gene are associated with clinical outcomes, comparing critically ill patients with sepsis from pneumonia vs those with extrapulmonary sepsis. Genetic association study. Medical/surgical ICUs in a tertiary-care, university-affiliated teaching hospital. Of 550 white patients with sepsis, 158 had pneumonia as the principle cause of their sepsis and 392 had an extrapulmonary source of sepsis. Haplotypes of the IL-10 gene were defined by measurement of haplotype tag single-nucleotide polymorphisms (SNPs). Primary outcome was 28-day survival. Secondary outcomes were days alive and free of organ dysfunction. Three SNPs in the IL-10 gene (-592 C/A, +734 G/T, and +3367 G/A) identified four major haplotypes: CGG, AGG, CTA, and CTG. Patients with pneumonia who carried one or two copies of the CGG haplotype had greater 28-day mortality (51.4%) than patients who did not carry this haplotype (29.1%, p = 0.007). Carriers of CGG had significantly more cardiovascular dysfunction (and use of vasopressors), renal dysfunction (and requirement of dialysis), hepatic dysfunction, and hematologic dysfunction (p < 0.05 in each case). In contrast, in patients with an extrapulmonary source of infection there was no significant association of the CGG haplotype (or any measured IL-10 genotype) with 28-day mortality or organ dysfunction. The IL-10 haplotype - 592C/734G/3367G is associated with increased mortality and organ dysfunction in critically ill patients with pulmonary sepsis but not in similarly ill patients with extrapulmonary sepsis. Therefore, polymorphisms within the IL-10 gene may be predictors of outcome in patients with sepsis from pneumonia.


Osteogenic magnesium incorporated into PLGA/TCP porous scaffold by 3D printing for repairing challenging bone defect.
Bone defect repair is a challenging clinical problem in musculoskeletal system, especially in orthopaedic disorders such as steroid associated osteonecrosis (SAON). Magnesium (Mg) as a biodegradable metal with properly mechanical properties has been investigating for a long history. In this study, Mg powder, poly (lactide-co-glycolide) (PLGA), β-tricalcium phosphate (β-TCP) were the elements to formulate a novel porous PLGA/TCP/Mg (PTM) scaffolds using low temperature rapid prototyping (LT-RP) technology. The physical characterization of PTM scaffold and Mg ions release were analyzed in vitro. The osteogenic and angiogenic properties of PTM scaffolds, as well as the biosafety after implantation were assessed in an established SAON rabbit model. Our results showed that the PTM scaffold possessed well-designed bio-mimic structure and improved mechanical properties. Findings of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and micro-computed tomography (micro CT)-based angiography indicated that PTM scaffold could increase blood perfusion and promote new vessel ingrowth at 4 weeks after surgery, meanwhile, a plenty of newly formed vessels with well-architective structure were observed at 8 weeks. Correspondingly, at 12 weeks after surgery, micro-CT, histological and mechanical properties analysis showed that PTM could significant enhance new bone formation and strengthen newly formed bone mechanical properties. The mean bone volume in PTM group was 56.3% greater than that in PT group. Biosafety assessments from 0 to 12 weeks after implantation did not induce increase in serum Mg ions concentration, and immune response, liver and kidney function parameters were all at normal level. These findings suggested that the PTM scaffold had both osteogenic and angiogenic abilities which were synergistic effect in enhancing new bone formation and strengthen newly formed bone quality in SAON. In summary, PTM scaffolds are promising composite biomaterials for repairing challenging bone defect that would have great potential for its clinical translation.


[Exercise-referral to a specialist in adapted physical activity (APA) : a pilot project].
Family physicians have a key role in the promotion of physical activity, in particular in identifying and counseling persons who have a sedentary lifestyle. Some patients could benefit from intensive individual counseling. Physicians are often not aware of all physical activity promotion activities in the community that they could recommend their patients. In a pilot study, we have tested and adapted the referral of patients from family physicians to specialists in adapted physical activity (APAs). APAs are trained to assess and guide persons towards physical activities adapted to their needs and pathologies and thus towards an increase in physical activity. Pilot data suggest that, while few patients were oriented to the APAs in the pilot project, family physicians appreciate the possibility of collaborating with the APAs.


Pre‑existing renal insufficiency synchronous with high preoperative neutrophil‑to‑lymphocyte ratio as a risk factor of intravesical recurrence in patients with pure upper tract urothelial carcinoma after radical nephroureterectomy.
The present study aimed to evaluate the influence of pre-treatment neutrophil-to-lymphocyte ratio (NLR) on bladder recurrence in patients with impaired renal function following radical nephrouretectomy (RNU) to treat pure upper tract urothelial carcinoma (UTUC). Retrospective data of 362 patients with pure UTUC who underwent RNU between 2008 and 2019 were analyzed. Kaplan-Meier analyses were performed to evaluate the association of preoperative NLR and estimation of the glomerular filtration rate (eGFR) with intravesical recurrence-free survival (IVRF). Furthermore, multivariate analyses were conducted to determine independent factors for predicting IVRF. In the retrospective cohort study of 362 patients, 103 patients (28%) had intravesical recurrence in a median follow-up of 50.1 months; among those, 85 (83%) developed bladder recurrence within two years after RNU. The Kaplan-Meier analysis indicated that patients exhibiting lower eGFR and higher NLR showed significantly poor IVRF rates (P=0.044). The simultaneous presence of eGFR <45 and NLR >3.8 was an independent factor for the shorter IVRF time in multivariate analysis with Cox's proportional hazards model. Most intravesical recurrences occurred within two years after RNU, particularly in pre-existing poor eGFR patients with preoperative high NLR. Moreover, pre-existing moderate to severe CKD synchronous with pre-operative NLR >3.8 was demonstrated as an independent factor for subsequent bladder recurrence in patients with pure UTUC following RNU. Therefore, such high-risk patients ought to be provided with close bladder monitoring during the follow-up.


Inhibitors of protein kinase C block the alpha 1-adrenergic refractoriness induced by phorbol 12-myristate 13-acetate, vasopressin and angiotensin II.
Vasopressin and angiotensin II inhibited in a dose-dependent fashion the stimulation of ureagenesis induced by alpha 1-adrenergic activation in hepatocytes incubated in medium without calcium and containing 25 microM EGTA. Vasopressin was more potent than angiotensin II. The effect of different inhibitors of protein kinase C on the alpha 1-adrenergic blockade induced by the vasopressor peptides was tested. It was observed that N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7), 4-aminoethyl-1-[2,3-bis(n-decloxyl)-n-propyl]-4-phenylpiperadin e dihydrochloride (CP-46,665-1); 8-(N,N-diethylamino)octyl-3,4, 5-trimethoxybenzoate (TMB-8), polymyxin B and 1-(5-isoquinolynsulfonyl)-2-methylpiperazine (H-7) block this effect of the vasopressor peptides in a dose-dependent fashion. The active phorbol ester, phorbol 12-myristate 13-acetate (PMA), also inhibited the alpha 1-adrenergic stimulation of ureagenesis in these cells. The inhibitors of protein kinase also blocked the effect of phorbol esters but a preincubation with the inhibitors before the addition of PMA was required. alpha 1-Adrenergic activation of phosphatidylinositol labeling was also abolished by PMA; the inhibitors of protein kinase partially blocked this effect of PMA. In summary, our data indicate that inhibitors of protein kinase C can block the alpha 1-adrenergic refractoriness induced by active phorbol esters, vasopressin and angiotensin II. The data are consistent with an important role of protein kinase C in modulating the alpha 1-adrenergic responsiveness of hepatocytes.


Control of Retrograde Signaling by Rapid Turnover of GENOMES UNCOUPLED1.
The exchange of signals between cellular compartments coordinates development and differentiation, modulates metabolic pathways, and triggers responses to environmental conditions. The proposed central regulator of plastid-to-nucleus retrograde signaling, GENOMES UNCOUPLED1 (GUN1), is present at very low levels, which has hampered the discovery of its precise molecular function. Here, we show that the Arabidopsis (Arabidopsis thaliana) GUN1 protein accumulates to detectable levels only at very early stages of leaf development, where it functions in the regulation of chloroplast biogenesis. GUN1 mRNA is present at high levels in all tissues, but GUN1 protein undergoes rapid degradation (with an estimated half-life of ∼4 h) in all tissues where chloroplast biogenesis has been completed. The rapid turnover of GUN1 is controlled mainly by the chaperone ClpC1, suggesting degradation of GUN1 by the Clp protease. Degradation of GUN1 slows under stress conditions that alter retrograde signaling, thus ensuring that the plant has sufficient GUN1 protein. We also find that the pentatricopeptide repeat motifs of GUN1 are important determinants of GUN1 stability. Moreover, overexpression of GUN1 causes an early flowering phenotype, suggesting a function of GUN1 in developmental phase transitions beyond chloroplast biogenesis. Taken together, our results provide new insight into the regulation of GUN1 by proteolytic degradation, uncover its function in early chloroplast biogenesis, and suggest a role in developmental phase transitions.


Engineering Ligninolytic Consortium for Bioconversion of Lignocelluloses to Ethanol and Chemicals.
Rising environmental concerns and recent global scenario of cleaner production and consumption are leading to the design of green industrial processes to produce alternative fuels and chemicals. Although bioethanol is one of the most promising and eco-friendly alternatives to fossil fuels yet its production from food and feed has received much negative criticism. The main objective of this study was to present the noteworthy potentialities of lignocellulosic biomass as an enormous and renewable biological resource. The particular focus was also given on engineering ligninolytic consortium for bioconversion of lignocelluloses to ethanol and chemicals on sustainable and environmentally basis. Herein, an effort has been made to extensively review, analyze and compile salient information related to the topic of interest. Several authentic bibliographic databases including PubMed, Scopus, Elsevier, Springer, Bentham Science and other scientific databases were searched with utmost care, and inclusion/ exclusion criterion was adopted to appraise the quality of retrieved peer-reviewed research literature. Bioethanol production from lignocellulosic biomass can largely satisfy the possible inconsistency of first-generation ethanol since it utilizes inedible lignocellulosic feedstocks, primarily sourced from agriculture and forestry wastes. Two major polysaccharides in lignocellulosic biomass namely, cellulose and hemicellulose constitute a complex lignocellulosic network by connecting with lignin, which is highly recalcitrant to depolymerization. Several attempts have been made to reduce the cost involved in the process through improving the pretreatment process. While, the ligninolytic enzymes of white rot fungi (WRF) including laccase, lignin peroxidase (LiP), and manganese peroxidase (MnP) have appeared as versatile biocatalysts for delignification of several lignocellulosic residues. The first part of the review is mainly focused on engineering ligninolytic consortium. In the second part, WRF and its unique ligninolytic enzyme-based bio-delignification of lignocellulosic biomass, enzymatic hydrolysis, and fermentation of hydrolyzed feedstock are discussed. The metabolic engineering, enzymatic engineering, synthetic biology aspects for ethanol production and platform chemicals production are comprehensively reviewed in the third part. Towards the end information is also given on futuristic viewpoints. In conclusion, given the present unpredicted scenario of energy and fuel crisis accompanied by global warming, lignocellulosic bioethanol holds great promise as an alternative to petroleum. Apart from bioethanol, the simultaneous production of other value-added products may improve the economics of lignocellulosic bioethanol bioconversion process.


Hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal malignancies using new hybrid CO2 system: preliminary experience in referral center.
The most frequent peritoneal surface malignancies originate principally by gastric cancer, colorectal cancer and ovarian cancer. Apart from the origin, peritoneal carcinosis (PC) is considered a negative prognostic factor. The hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal malignancies is considered an attractive method to deliver chemotherapy with enhanced effect directly at the tumor site. The use of such loco-regional approach has proved to improve prognosis of peritoneal carcinomatosis from different origins. Recently, new devices are suitable for loco-regional intraperitoneal chemotherapy as Peritoneal Recirculation System (PRS-1.0 Combat) with CO2 technology. This is a retrospective study with the aim to assess the perioperative outcomes using PRS. Seventeen patients were enrolled affected by colorectal or ovarian cancer. Complete cytoreduction (RT = 0) was achieved for all cases. Median operative time was 420 min (range: 335-665) and median drugs dose used for HIPEC was 137 mg/m2 (115-756). Median EBL was 200 ml (range 50-1000). Median post-operative hospital stay was 9 days (range: 4-24). Treatment-related early complications were recorded in 8 (47.0%) cases and were G1-G2 Major complications occurred in two (11.7%) cases. Considering our aim to test the PRS in different cases and in different pathologies, the results confirmed that the technique is feasible with good perioperative outcomes.


Hypoxia-induced downregulation of B-cell translocation gene 3 confers resistance to radiation therapy of colorectal cancer.
Colorectal cancer (CRC) is now a major human cancer, and B-cell translocation gene 3 (BTG3) has been reported as a tumor-suppressor in CRC, but its upstream regulator has not been identified. Endogenous expression levels of BTG3 were compared between normal colorectal cell line CCD-18Co and two CRC cell lines SW480 and HT29, as well as between CRC patient tumor and adjacent normal tissues. Analysis of BTG3 genomic region was performed which identified a putative hypoxia response element (HRE). Effects of hypoxia condition, BTG3 overexpression, and their combination on the radiation sensitivity of CRC cell lines were assessed. BTG3 was downregulated in CRC cell lines and patient tumor samples, via the HRE in its promoter region. Hypoxia and BTG3 overexpression could both induce radiation resistance in CRC cells. Combining hypoxia with BTG3 overexpression effectively rendered the resistance of CRC cells to radiation to a level lower than hypoxia alone and higher than normoxia alone, indicating the essential role of BTG3 in hypoxia-induced radiation resistance of CRC cells. We therefore propose a novel signaling cascade involving hypoxia/BTG3 to be a potential risk factor for CRC patients undergoing radiation therapy, which could possibly serve as therapeutic targets among CRC patients with acquired radiotherapy resistance.


Factors that affect nurse practitioners' implementation of evidence-based practice.
Evidence-based practice (EBP) is a key recommendation to improve patient care outcomes. Factors that influence nurse practitioners' (NPs) ability to implement EBP in the clinical setting have not been fully explored. The study sought to explore NPs' practice, professional, and personal variables with self-reported ability to implement EBP. The study was a correlational, cross-sectional design with a survey data collection methodology. A survey was mailed to 1200 randomly selected clinically practicing NPs, which included the Evidence-Based Education Questionnaire (EBEQ). A total of 480 surveys were returned, which represented a 40% response rate. Statistical analyses were performed to explore relationships between NPs' demographics and EBEQ scores. The DNP appears to have additive benefit for self-perceived ability to implement EBP in the clinical setting when compared to the master's degree educated NP. NPs' gender, age, and number of hours worked weekly also correlated to EBEQ scores. NPs' practice settings, such as Magnet status designation and employment at an academic center also significantly correlated to EBEQ scores. Other practice setting variables, such as where the practice is located, did not significantly correlate to EBEQ scores. The findings of this study provide foundational knowledge to enable increasing NPs' EBP in the clinical setting.


A Review of Treatment-Related Outcomes in Female Partners of Men With Peyronie's Disease-An Opportunity for Improved Assessment.
Peyronie's disease (PD) is a disorder of the penile tunica albuginea, causing penile deformity, shortening, pain, and sexual dysfunction. While studies have shown treatment efficacy for patients, research on treatment-related outcomes for sexual partners is lacking. We sought to review the literature on clinical characteristics and treatment-related outcomes from the perspective of female sexual partners of PD patients. We performed a comprehensive literature search of PubMed, Embase, and MEDLINE databases to identify all studies pertaining to PD and partner satisfaction through December 2019. 13 articles that discussed partner satisfaction with treatments of PD including oral, intralesional, and surgical therapy were found in the literature review. At baseline, female partners of men with PD report lower sexual satisfaction and dyspareunia. Results showed that intralesional injection of collagenase Clostridium histolyticum resulted in partner satisfaction in approximately 70% of patients based on differing definitions. Penile plication demonstrated variable partner satisfaction ranging from 34% to 88% whereas plaque incision or partial excision with grafting achieved rates ranging from 90% to 100%. Penile prosthesis implantation resulted in partner satisfaction rates ranging from 40% to 75%. PD has a negative impact on psychological and emotional well-being for both patients and their female partners. Surgical and non-surgical treatment for PD has the ability to improve sexual satisfaction of partners. Studies discussed focus on the various forms of treatment for men with PD; however, the available studies were notably limited by small sample sizes, inconsistent use of validated questionnaires, and lack of control groups. In addition, the topic of partner satisfaction discussed in the articles mainly examined the response of female partners and did not discuss effects of the disease on male partners. Clinicians should consider carefully screening PD partners for sexual dysfunction to optimize couple-focused therapy. Further studies are needed to evaluate effects on male sexual partners of PD patients. Parikh NN, Heslop DL, Bajic P, et al. A Review of Treatment-Related Outcomes in Female Partners of Men With Peyronie's Disease-An Opportunity for Improved Assessment. J Sex Med 2020;8:548-560.


[Marihuana psychoses].
Five chronic consumers of marihuana (through periods of 1 to 3 years) were studied and given a complete set of psychological tests (Rorschach, Wechsler, Phillipson, Psicodiagnóstico Miokinético). Brief case histories and tests results are presented for each subject. In all cases, marked depression, and anxiety, schizoid features, and poor control were detected. In four patients self-aggresion, inversion of sleep cycle, weakness of will and mental confusion were registered. In four subjects a definite psychotic profile was detected through Rorschach tests. Three patients suffered from visual hallucinations, and trends to sexual promiscuity. Memory failure and gaps were apparent in two cases. One patient developed a short-lasting paranoid delusion. Two patients showed no sign of abnormality in their E.E.G. The syndrome shows that marihuana abuse may lead to toxic psychosis similar to schizophrenia. The importance of a systematic use of complete sets of psychological tests is discussed, although their value for a differential diagnosis between toxic marihuana-psychosis and schizophrenia remains to be established. The need for careful search on marihuana abuse is emphasized. Regarding the physiopathology of marihuana-psychosis, some recent findings of neurochemistry are discussed, in particular those of biological theories of schizophrenia. This approach allows a parallel between both disorders. The possibility of both being accounted for by a common metabolic defect is suggested. Finally, the current contention that marihuana is harmless or innocuous is called to revision.