Pixantrone demonstrates significant in vitro activity against multiple myeloma and plasma cell leukemia.
Treatment results for multiple myeloma and plasma cell leukemia have considerably improved, but cure remains elusive and establishing new therapeutic approaches constitutes a major unmet clinical need. We analyzed the anti-myeloma properties of the aza-anthracenedione pixantrone which has been successfully used in a phase III study for the treatment of patients with aggressive non-Hodgkin's lymphoma as monotherapy as well as in combination regimes in vitro and in an adapted in vivo model (ex ovo chicken chorioallantoic membrane (CAM) assay). Pixantrone significantly inhibited proliferation and metabolic activity of all investigated myeloma cell lines. Importantly, anti-myeloma effects were more pronounced in tumor cell lines than in stromal cells, mesenchymal stem cells, and peripheral blood mononuclear cells of healthy controls. Apoptosis of myeloma cell lines was observed only after a 7-day incubation period, indicating a fast cytostatic and a slower cytotoxic effect of this drug. Pixantrone reduced the viability of primary plasma cells of patients and induced downregulation of myeloma-cell growth in the CAM assay. Additionally, we demonstrate in vitro synergism between pixantrone and the histone deacetylase inhibitor panobinostat with respect to its anti-proliferative features. From these data, we conclude that systematic investigations of the clinical usefulness of pixantrone in the framework of controlled clinical trials are clearly indicated (e.g., in penta-refractory patients).


Identification of three transcriptional regulatory elements in the rat mitochondrial benzodiazepine receptor-encoding gene.
The sequence upstream from the first exon in the rat mitochondrial benzodiazepine receptor-encoding gene (MBR) was analyzed for transcriptional promoter activity by three techniques: promoter deletion analysis in vectors containing the gene cat encoding chloramphenicol acetyltransferase, electrophoretic mobility shift analysis (EMSA) and DNase I protection assay. All three methods are in uniformity with the identification of at least three regulatory elements corresponding to locations -51/-33, -267/-249 and -555/-526. The most distal and proximal domains are positive-acting, whereas the element at -267/-249 acts in a negative manner. The positive-acting -51/-33 element contains the middle of three consensus Sp1-recognition sequences found in this region of the gene. Binding of Y1 cell nuclear protein to a DNA fragment corresponding to this region of the gene is competed by a synthetic oligodeoxyribonucleotide bearing the consensus Sp1-binding site sequence. These studies provide the first reported functional evidence localizing transcriptional elements of MBR.


Temperature effects on the structure of poly(dA).poly(dT): an X-ray fiber diffraction study.
X-ray fiber diffraction of poly(dA).poly(dT) subjected to variation in the relative humidity, has allowed us to demonstrate the effects of temperature on the conformation of the polynucleotide. When the temperature of the poly(dA).poly(dT) is greater than 30 degrees C and the relative humidity near 80%, a new diffraction pattern is obtained. We observe a transition between the classical alpha B' form of poly(dA).poly(dT) and a double helical structure, B*, which remains stable at a temperature up to 70 degrees C. This new conformation of poly(dA).poly(dT) is a right-handed double helix with 11.4 nucleotide pairs per turn and a pitch of 36.7 A.


Determination of the physical state of a drug in amorphous solid dispersions using artificial neural networks and ATR-FTIR spectroscopy.
The objective of the present study was to evaluate the use of artificial neural networks (ANNs) in the development of a new chemometric model that will be able to simultaneously distinguish and quantify the percentage of the crystalline and the neat amorphous drug located within the drug-rich amorphous zones formed in an amorphous solid dispersion (ASD) system. Attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy was used, while Rivaroxaban (RIV, drug) and Soluplus® (SOL, matrix-carrier) were selected for the preparation of a suitable ASD model system. Adequate calibration and test sets were prepared by spiking different percentages of the crystalline and the amorphous drug in the ASDs (prepared by the melting - quench cooling approach), while a 24 full factorial experimental design was employed for the screening of ANN's structure and training parameters as well as spectra region selection and data preprocessing. Results showed increased prediction performance, measured based on the root mean squared error of prediction (RMSEp) for the test sample, for both the crystalline (RMSEp (crystal) = 0.86) and the amorphous (RMSEp (amorphous) = 2.14) drug. Comparison with traditional regression techniques, such as partial least square and principle component regressions, revealed the superiority of ANNs, indicating that in cases of high structural similarity between the investigated compounds (i.e., the crystalline and the amorphous forms of the same compound) the implementation of more powerful/sophisticated regression techniques, such as ANNs, is mandatory.


Sociodemographic and disease-related determinants of return to work among women with breast cancer: a German longitudinal cohort study.
Return to work (RTW) is a key parameter of outcome quality that ensures social participation. Therefore, this study analyses the sociodemographic and disease-related determinants of RTW among newly diagnosed breast cancer patients. In a prospective, multicentre cohort study, breast cancer patients were surveyed three times: directly after surgery, after 10 weeks, and after 40 weeks. Logistic regression analysis was applied to estimate the association of RTW at 40 weeks following discharge with sociodemographic and disease-related characteristics (n = 577). The sociodemographic variables "entrance certificate at a university of applied science" compared to "university entrance certificate" (OR = 3.1, 95%-CI = 1.2-8.1), age group "55-59 years" compared to "18-44 years" (OR = 3.2, 95%-CI = 1.2-8.4) and "having children" (OR = 2.8, 95%-CI = 1.2-6.2) as well as the disease-related variables "rehabilitation" (OR = 0.5, 95%-CI = 0.3-0.9), self-rated health "good" and "excellent" compared to "bad" (OR = 2.7, 95%-CI = 1.4-5.5; OR = 11.6, 95%-CI = 4.2-31.8) and the UICC-classification "stage II" and "stage III/IV" in comparison to "stage 0/I" (OR = 0.5, 95%-CI = 0.3-0.8; OR = 0.2, 95%-CI = 0.1-0.5) significantly affect RTW among breast cancer patients (Nagelkerke's Pseudo-R2 = 0.275). The findings show that significant differences in RTW exist between patient groups and suggest that RTW issues must be addressed more effectively before, during and after treatment. For future research on RTW in Germany, longitudinal studies with a follow-up of several years are necessary. Information and support deficits should be tackled by social services or breast care nurses. Database Health Services Research, VfD_PIAT_12_001630 , registered 01.03.2012.


Phenothiazinium-based photobactericidal materials.
Photosensitisers based on the phenothiazinium chromophore have been reported to be bactericidal on illumination via a singlet oxygen-mediated mechanism. The current work reports on the immobilisation of the methylene blue analogue, new methylene blue, in polymer resins, and the preliminary development of photobactericidal materials. The resultant materials exhibited measurable levels of singlet oxygen and were photobactericidal against both Staphylococcus epidermidis and Escherichia coli. Such materials may be of use in surface disinfection/infection control in the healthcare milieu.


Elite athletes maintain peak performance after testing positive for SARS-CoV-2.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has to date resulted in more than 200 million cases and more than four million deaths. Following a few months of hiatus, as part of the initial response to the pandemic, professional sporting activities resumed throughout the world. To ensure a safe return-to-play, the effects of SARS-CoV-2 infections on elite athletes were carefully monitored. Several elite professional athletes tested positive for SARS-CoV-2. A few reports of persistent and residual symptoms of infections emerged. However, peak athletic performance in elite athletes did not seem to be affected, with some athletes recording historical performances both in the weeks following as well as several months after contracting the novel coronavirus. This manuscript presents these data along with a discussion on the potential protective mechanisms in athletes. These findings raise further awareness about the importance of performing regular physical activity and maintaining a favourable body composition and overall fitness, and emphasise the need for public health initiatives and actions to promote a healthy lifestyle on a population level. Given that SARS-CoV-2, with its mutations, will be a chronic public health issue, preventive medicine measures such as advocacy and incentives to lead a healthy lifestyle are warranted as another shield, along with vaccines, in the arsenal against SARS-CoV-2.


Corrigendum to "Remodeling tumor immunosuppressive microenvironment via a novel bioactive nanovaccines potentiates the efficacy of cancer immunotherapy" [Bioactive Mater. 16 107-119].
[This corrects the article DOI: 10.1016/j.bioactmat.2022.03.008.].


Absorption of flurbiprofen in the fed and fasted states.
The oral absorption of flurbiprofen, an antiinflammatory nonsteroidal compound, was compared in the fasted vs the fed state. When ingested as an aqueous solution of the sodium salt, absorption kinetics followed a monoexponential pattern in half of the subjects and a bimodal pattern with a lag time before the onset of the second phase of absorption in the other half of the subjects. When ingested in the free acid form as a tablet either with water (fasted state) or with water 15 min after 330 ml of apple juice (fed state), flurbiprofen absorption was always bimodal, and the lag time before the onset of the second phase was shown to be dependent on the gastric emptying time (r = 0.623, P less than 0.01). The gastric emptying times were significantly longer when the drug was administered in the fed state (average GET = 57 min in the fasted state and 102 min in the fed state; P less than 0.01). These results suggest that gastric emptying effects are one important way in which absorption of drugs can be affected by meal intake.


Transverse rectus abdominis myocutaneous flap for postpneumonectomy bronchopleural fistula: A case report.
Numerous types of flap coverage have been reported to prevent or to repair bronchopleural fistulas. Most of the flaps were harvested from chest area. However, these pedicled flaps might not be optimal for the patient who has undergone previous radiotherapy on pulmonary parenchyma because the pedicle artery of the flap might have been injured by irradiation. Therefore, an alternative flap outside of the chest area is necessary. A 61-year-old male was diagnosed of squamous cell carcinoma in right upper lobe lung (cT3N2M0, stage IIIa). After completing the neoadjuvant chemoradiotherapy, he underwent video-assisted thoracoscopic surgery with right side intrapericardial pneumonectomy. Persistent air leak due to postpneumonectomy bronchopleural fistula. Pedicled transverse rectus abdominis myocutaneous (TRAM) flap was used to repair the bronchial stump. The bronchial stump was repaired successfully, the bronchopleural fistula was obliterated, and the patient was free from air leak after following for 12 months. This case demonstrated that pedicled TRAM flap is a feasible alternative to repair bronchopleural fistula.


Effect of pulmonary hypertension on survival in patients with idiopathic pulmonary fibrosis after lung transplantation: an analysis of the United Network of Organ Sharing registry.
Pulmonary hypertension (PH) is a comorbidity associated with idiopathic pulmonary fibrosis (IPF). There is limited research regarding the effect on survival after lung transplantation (LTx). To assess the effect of PH on survival in patients with IPF who received LTx, the United Network for Organ Sharing was queried for eligible patients with recorded mean (PAmean) and systolic (PAsystolic) pulmonary artery pressure. The analysis was restricted to the post-lung allocation scoring system starting May 1, 2005, to provide a cohort receiving present-day therapies and management. The last update of the data set was July 6, 2012, so a cutoff date of July 6, 2011, was chosen to allow for the possibility of at least 1 year of follow-up. Thresholds of ≥25 and ≥35 mm Hg were chosen for PAmean and PAsystolic, respectively, as indicators of PH. Of 23,951 LTxs in the UNOS data set, 2,542 met inclusion criteria, 1,234 (49%) with PAmean ≥ 25 mm Hg and 1,680 (66%) with PAsystolic ≥ 35 mm Hg. PAmean and PAsystolic were highly correlated, with an estimated correlation coefficient ρ = 0.93 (p < 0.001). Patients with PH (PAmean ≥ 25 mm Hg or PAsystolic ≥ 35 mm Hg) tended to have higher ischemic times, lung allocation score values, forced vital capacity percentage predicted at LTx, and supplemental oxygen requirement at rest values. In addition, a larger proportion of patients with PH was African American, male, had diabetes, and received bilateral LTx compared with single LTx. Comparing PAmean < 25 vs ≥ 25 mm Hg and PAsystolic < 35 vs ≥ 35 mm Hg, median survival in months was 60.4 (95% confidence interval [CI], 55.2-80.4) vs 61.4 (95% CI, 56.9-66.9; log-rank p = 0.876) and 57.6 (95% CI, 50.9-68.0) vs 64.3 (95% CI, 57.5-71.3; log-rank p = 0. 247), respectively. Hazard ratios for both definitions of PH from univariable and multivariable Cox proportional hazard models were close to 1 and none were statistically significant. On the basis of our models and despite PH being prevalent, there is no strong evidence suggesting that PH significantly alters the risk of death in IPF patients after LTx.


Implementation and use of mHealth home telemonitoring in adults with acute COVID-19 infection: a scoping review protocol.
mHealth refers to digital technologies that, via smartphones, mobile apps and specialised digital sensors, yield real-time assessments of patient's health status. In the context of the COVID-19 pandemic, these technologies enable remote patient monitoring, with the benefit of timely recognition of disease progression to convalescence, deterioration or postacute sequelae. This should enable appropriate medical interventions and facilitate recovery. Various barriers, both at patient and technology levels, have been reported, hindering implementation and use of mHealth telemonitoring. As systematised and synthesised evidence in this area is lacking, we developed this protocol for a scoping review on mHealth home telemonitoring of acute COVID-19. We compiled a search strategy following the PICO (Population, Intervention, Comparator, Outcome) and PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendation for Scoping Reviews) guidelines. MEDLINE, Embase and Web of Science will be searched from 1 March 2020 to 31 August 2021. Following the title and abstract screening, we will identify, systematise and synthesise the available knowledge. Based on pilot searches, we preview three themes for descriptive evidence synthesis. The first theme relates to implementation and use of mHealth telemonitoring, including reported barriers. The second theme covers the interactions of the telemonitoring team within and between different levels of the healthcare system. The third theme addresses how this telemonitoring warrants the continuity of care, also during disease transition into deterioration or postacute sequelae. The studied evidence is in the public domain, therefore, no specific ethics approval is required. Evidence dissemination will be via peer-reviewed publications, conference presentations and reports to the policy makers.


Mt-fura-2, a Ratiometric Mitochondria-Targeted Ca2+ Sensor. Determination of Spectroscopic Properties and Ca2+ Imaging Assays.
Ca2+ handling by mitochondria is implicated in energy production, shaping of cytosolic Ca2+ rises, and determination of cell fate. It is therefore of crucial interest for researchers to directly measure mitochondrial Ca2+ concentration [Ca2+] in living cells. Synthetic fluorescent Ca2+ indicators, providing a straightforward loading technique, represents a tempting strategy. Recently, we developed a new highly selective mitochondria-targeted Ca2+ indicator named mt-fura-2 , obtained by coupling two triphenylphosphonium cation-containing groups to the molecular backbone of the cytosolic ratiometric Ca2+ indicator fura-2 .The protocols we describe here cover all the significant steps that are necessary to characterize the probe and apply it to biologically relevant contexts. The procedures reported are referred to mt-fura-2 but could in principle be applied to characterize other mitochondria-targeted Ca2+ probes . More in general, with the due modifications, this chapter can be considered as a handbook for the characterization and/or application of mitochondria-targeted chemical Ca2+ probes .


Treatment parameters of desensitization to capsaicin.
Desensitization of sensory afferents with topical capsaicin has been employed to treat a variety of neuropathic disorders in humans, however, few studies have been undertaken to systematically evaluate treatment parameters to determine the optimal dose and frequency of treatment needed to achieve and maintain desensitization. The effects of several treatment parameters, including dose, number of exposures, interval between exposures and duration of exposure, on the development, magnitude and duration of desensitization following local treatment with capsaicin and related compounds are described.


Risk factors for residual back pain following percutaneous vertebral augmentation: the importance of paraspinal muscle fatty degeneration.
Residual back pain (RBP) after percutaneous vertebral augmentation (PVA) still exists considerable, and it even affects daily life due to moderate or severe back pain. A variety of risk factors have been previously identified for developing residual back pain. However, there are conflicting reports regarding the association between sarcopenia and residual back pain. As such, the aim of this study was to investigate whether paraspinal muscle fatty degeneration is a predictor of residual back pain. We retrospectively reviewed the medical records of patients with single-segment OVCF who underwent PVA from January 2016 to January 2022. Patients were divided into RBP group (86 patients) and control group (790 patients) according to whether the visual analog scale (VAS) score ≥ 4. The clinical and radiological data were analyzed. Paraspinal musculature fatty degeneration was measured using the Goutallier classification system (GCS) at the L4 - 5 intervertebral disc level. Univariate and multivariate logistic regression analyses were performed to identify risk factors. The results of multivariate logistical regression analysis revealed that posterior fascia injury (odds ratio (OR) = 5.23; 95% confidence interval (CI) 3.12-5.50; P < 0.001), as regards paraspinal muscle fatty degeneration, including Goutallier grading (OR = 12.23; 95% CI 7.81-23.41; P < 0.001), fCSA (OR = 3.06; 95% CI 1.63-6.84; P = 0.002), fCSA/CSA (%) (OR = 14.38; 95% CI 8.80-26.29; P < 0.001), and facet joint violation (OR = 8.54; 95% CI 6.35-15.71; P < 0.001) were identified as independent risk factors for RBP. Posterior fascia injury, paraspinal muscle fatty degeneration, and facet joint violation were identified as independent risk factors for RBP, with paraspinal muscle fatty degeneration playing an important role.


The predatory behaviour of a tramp ant species in its native range.
Workers of the pest ant Paratrechina longicornis participate in a type of group hunting. Each individual forages with its long antennae wide open and moves quickly (6.3 cm/s) along an erratic path surrounded by nestmates behaving in the same way and within range of a recruiting pheromone. They detect prey by contact with successful workers singly capturing and retrieving small prey and seizing larger ones by an appendage. Then they recruit nestmates at short-range; all together they spread-eagle the prey and retrieve them whole.


Transplantation of R-GSIK scaffold with mesenchymal stem cells improves neuroinflammation in a traumatic brain injury model.
Neural tissue engineering has been introduced as a novel therapeutic strategy for traumatic brain injury (TBI). Transplantation of mesenchymal stem cells (MSCs) has been demonstrated to improve functional outcome of brain injury, and RADA4GGSIKVAV (R-GSIK), a self-assembling nano-peptide scaffold, has been suggested to promote the behavior of stem cells. This study was designed to determine the ability of the R-GSIK scaffold in supporting the effects of MSCs on motor function activity and inflammatory responses in an experimental TBI model. A significant recovery of motor function was observed in rats that received MSCs+R-GSIK compared with the control groups. Further analysis showed a reduction in the number of reactive astrocytes and microglial cells in the MSCs and MSCs+R-GSIK groups compared with the control groups. Furthermore, western blot analysis indicated a significant reduction in pro-inflammatory cytokines, such as TLR4, TNF, and IL6, in the MSCs and MSCs+R-GSIK groups compared with the TBI, vehicle, and R-GSIK groups. Overall, this study strengthens the idea that the co-transplantation of MSCs with R-GSIK can increase functional outcomes by preparing a beneficial environment. This improvement may be explained by the immunomodulatory effects of MSCs and the self-assembling nano-scaffold peptide.


Fed-batch cultivation of Desmodesmus sp. in anaerobic digestion wastewater for improved nutrient removal and biodiesel production.
Desmodesmus sp. was used in anaerobically digested wastewater (ADW) for nutrients removal and the biodiesel production was measured and compared using fed-batch cultivation was investigated and compared with batch cultivation. The Desmodesmus sp. was able to remove 236.143, 268.238 and 6.427 mg/L of TN, NH4-N and PO4-P respectively after 40 d of fed-batch cultivation, while in batch cultivation the quantities of TN, NH4-N and PO4-P removed were 33.331, 37.227 and 1.323 mg/L. Biomass production of Desmodesmus sp. was also enhanced in fed-batch cultivation, when ADW loading was carried out every 2 days; the biomass concentration peaked at 1.039 g/L, which was three times higher than that obtained in batch cultivation (0.385 g/L). The highest lipid production (261.8 mg/L) was also recorded in fed-batch cultivation as compared to batch cultivation (83.3 mg/L). Fed-batch cultivation of Desmodesmus sp. could provide effective control of nutrients limitation and/or ammonia inhibition on microalgae cultivation.


Condom usage by a population of delinquent southern male adolescents.
Of sexually active delinquent male adolescents admitted to a detention facility over a 6-month period from 1987 to 1988, 69% reported condom usage. Review of the medical records of a similar group of detainees from the same facility in 1984 revealed a 44% reported condom usage rate, suggesting a marked increase in utilization. Stated reasons for condom use in 1987-1988 included prevention of sexually transmitted diseases (63%) and pregnancy (33%). More than one reason was given by 20%.


Predictive Risk Factors Associated With Increased Opioid Use Among Patients Undergoing Elective Spine Surgery.
Opioids are commonly used for postoperative pain management in spine surgery. However, few guidelines exist for appropriate prescribing in the acute postoperative phase of care. We identify risk factors for inpatient (IP) opioid use and examine relationships between IP requirements and discharge (DC) opioid prescriptions. Retrospective review of elective spine surgeries between January 2014 and May 2018 identified cases of lumbar decompression (LD), LD with fusion (LDF), and cervical decompression with fusion (CDF) at our high-volume spine center. Multiple regression examining potential risk factors for opioid use was performed. Opioid use was normalized into daily morphine milligram equivalents (MME). A total of 2281 patients who underwent 1251 LD, 384 LDF, and 648 CDF procedures were identified (54.1% male, mean age = 57.9 years, mean body mass index = 30.3 kg/m2, median American Society of Anesthesiologists [ASA] score = 2). Mean IP opioid use was 44.4 MME/day and average DC prescriptions totaled 496.5 MME. Multiple regression models identified younger age and increased ASA score as predictive of increased daily IP opioid consumption (βAGE = -0.36, P < .001, βASA = 10.1, P < .001; R 2 = 0.308) and increased DC opioid amounts (βAGE = -4.62, P < .001, βASA = 72.1, P < .001; R 2 = 0.097). Highest IP and DC opioid use was observed among LDF followed by CDF and LD patients. Significant positive correlations were found between IP opioid usage and DC opioid prescriptions by IP opioid quartiles (r = 0.99 LD, 0.98 LDF, 0.96 CDF). Younger patients and higher ASA scores correlated with increased IP opioid use and DC opioid prescriptions. DC prescriptions appropriately reflect IP use. 3. Adequate pain management is an integral component to successful outcomes in spine surgery. Awareness of candidates likely to require higher levels of opioid analgesia will be beneficial in guiding surgeon prescribing practices.


Petrogenesis of isotopically enriched Quaternary magma with adakitic affinity associated with subduction of old lithosphere beneath central Myanmar.
We present a model for the petrogenesis of magma with adakitic affinity in an old subduction zone, which does not involve slab melting and is constrained by new geochronological and geochemical data for Mt. Popa, the largest of three Quaternary volcanoes in central Myanmar (Popa, Monywa and Singu). The edifice is composed of Popa Plateau (0.8-0.6 Ma) with high-K rocks and a stratovolcano (< 0.33 Ma) predominantly composed of medium-K rocks with adakitic affinity (Mg# 45-63, Sr/Y > 40). The distinct K contents indicate that the adakitic magmas cannot be derived from Popa high-K rocks, but they share trace-element signatures and Sr-Nd isotope ratios with medium-K basalts from Monywa volcano. Our estimation of water contents in Popa magma reveals that primary magma for medium-K basalts was generated by partial melting of wedge mantle with normal potential temperature (TP 1330-1340 °C) under wet conditions (H2O 0.25-0.54 wt%). Its melting was probably induced by asthenospheric upwelling that is recognized by tomographic images. Mafic adakitic magma (Mg# ~ 63, Sr/Y ~ 64) was derived from the medium-K basaltic magma in fractional crystallization of a garnet-bearing assemblage at high pressure, and felsic adakitic rocks (Mg# ~ 45, Sr/Y ~ 50) were produced by assimilation-fractional crystallization processes at mid-crustal depths.


Lithiation and Sodiation of Hydrogenated Silicene: A Density Functional Theory Investigation.
The next-generation renewable energy machineries necessitate the electrodes with appropriate electrochemical performance. Here, the anodic properties of silicane for Li- and Na-ion batteries were scrutinized employing first-principle calculations. The projected single-layer hydrogen-functionalized Si (Si2 H2 ) structure was energetically, mechanically, dynamically, and thermally stable based on theoretical simulations, confirming its experimental feasibility. The electronic properties revealed the semiconducting nature of silicane on the basis of PBE and HSE06 schemes with an indirect bandgap. As anode material for Li- and Na-ion batteries, hydrogenated silicene showed promising electrochemical performance because of the proper adsorption strength between Si2 H2 and the adsorbed Li and Na. The average open circuit voltages for Li2x Si2 H2 and Na2x Si2 H2 were as low as 0.42 and 0. 64 V, while its specific capacity was as high as 921 and 1842 mAh g-1 for Li and Na, respectively. It also showed ultra-fast diffusion channels for Li and Na ions. The diffusion barriers for Li and Na migrations were as low as 0.18 and 0.14 eV, respectively, which revealed rapid charge/discharge processes using hydrogenated silicene as anode. These important features facilitate silicane as favorable anode material for Li/Na-ion batteries.


Ethical Issues in Research: Perceptions of Researchers, Research Ethics Board Members and Research Ethics Experts.
In the context of academic research, a diversity of ethical issues, conditioned by the different roles of members within these institutions, arise. Previous studies on this topic addressed mainly the perceptions of researchers. However, to our knowledge, no studies have explored the transversal ethical issues from a wider spectrum, including other members of academic institutions as the research ethics board (REB) members, and the research ethics experts. The present study used a descriptive phenomenological approach to document the ethical issues experienced by a heterogeneous group of Canadian researchers, REB members, and research ethics experts. Data collection involved socio-demographic questionnaires and individual semi-structured interviews. Following the triangulation of different perspectives (researchers, REB members and ethics experts), emerging ethical issues were synthesized in ten units of meaning: (1) research integrity, (2) conflicts of interest, (3) respect for research participants, (4) lack of supervision and power imbalances, (5) individualism and performance, (6) inadequate ethical guidance, (7) social injustices, (8) distributive injustices, (9) epistemic injustices, and (10) ethical distress. This study highlighted several problematic elements that can support the identification of future solutions to resolve transversal ethical issues in research that affect the heterogeneous members of the academic community.


Comprehensive toxicology screening in the emergency department: an aid to clinical diagnosis.
An audit of 2,641 toxicology requests from the Georgetown University Hospital Emergency Department from 1981 through 1984 was conducted to assess the contribution of toxicology laboratory results to the clinical evaluation of the intoxicated patient. Positive findings were obtained in 80% of the patients tested. Ethanol was the most common intoxicant, accounting for 48% of all positive results and an average serum concentration of 250 mg/dl. Multiple drug use was documented in 28% of the patients with positive results; some ingested as many as six substances. Women were more likely than men to be polydrug users. A comparison of laboratory findings with diagnosis based on history and examination for 76 patients revealed that the laboratory provided additional information on the nature of the intoxication two-thirds of the time. Our conclusion is that the toxicology laboratory offering a broadly based screening service when properly utilized by the emergency department staff can aid in establishing an accurate diagnosis and provide a guide to therapy in the intoxicated patient.


Burden of falls among elderly persons in India: A systematic review and meta-analysis.
. Falls are one of the leading causes of death and disability among elderly persons. In India, there is paucity of data on the prevalence of falls, particularly among community-dwelling elderly persons. To estimate healthcare costs related to falls and formulation of fall prevention strategies, there is a need of reliable estimates of magnitude of falls. We aimed to provide a community-based pooled estimate of the burden of falls among elderly persons in India. . A systematic literature search was done manually as well as electronically through PubMed, Google Scholar, Cochrane library, IndMed, Embase and WHO databases. Community-based original studies conducted in India were included. No restriction for the date was used. Meta-analysis was done using the random effects model. . Sixteen studies were included in the review and meta-analysis. These studies included a total of 14 844 elderly persons, of which 2707 reported falling. The pooled prevalence of falls was found to be 31% (95% CI 23%-39%). There was significant heterogeneity between the studies (I2 = 98.08%, p<0.01). . There is a high prevalence of falls among elderly persons in India. However, the available studies have considerable methodological variations and are of limited quality. Realistic estimates are required for designing programmes for prevention of falls and for rehabilitation.


What the salamander eye has been telling the vision scientist's brain.
Salamanders have been habitual residents of research laboratories for more than a century, and their history in science is tightly interwoven with vision research. Nevertheless, many vision scientists - even those working with salamanders - may be unaware of how much our knowledge about vision, and particularly the retina, has been shaped by studying salamanders. In this review, we take a tour through the salamander history in vision science, highlighting the main contributions of salamanders to our understanding of the vertebrate retina. We further point out specificities of the salamander visual system and discuss the perspectives of this animal system for future vision research.


Sitagliptin more effectively achieves a composite endpoint for A1C reduction, lack of hypoglycemia and no body weight gain compared with glipizide.
Sitagliptin and glipizide added to metformin provided similar degrees of glycemic efficacy in patients with type 2 diabetes with inadequate glycemic control on metformin monotherapy at 1 year; however, significantly more patients in the sitagliptin group achieved an A1C reduction of >0.5% without hypoglycemia and without an increase in body weight.


Guanosine Assembly Enabled Gold Nanorods with Dual Thermo- and Photoswitchable Plasmonic Chiroptical Activity.
Noble metal nanostructures with plasmonic circular dichroism (PCD) have attracted interest, and a modulation of PCD is of great importance for their potential applications. Herein, we propose a supramolecular strategy for achieving dual thermal and photoswitchable PCD. When guanosine (G), deoxyguanosine (dG), and boric acid modified achiral gold nanorods (GNRs) were coassembled into a hydrogel, hybrid nanofibers with PCD were produced. When the hydrogel was heated, the nanofiber was disassembled and the PCD disappeared. As the hydrogel was thermally reversible, a thermo-controlled PCD could be realized. The hybrid hydrogel also showed photoswitchable PCD. When the gel was irradiated with an IR laser, the PCD disappeared. It can be restored by being placed at room temperature. Moreover, the hybrid gel was selectively responsive to the circularly polarized light (CPL). For (G/dG)-GNR hybrid assemblies, the R-CPL irradiation showed photothermal efficiency higher than that of L-CPL, which made it useful for an IR-irradiation-controlled release of drug molecules.


[Diagnosis of varices in liver cirrhosis: duplex ultrasound versus gastroscopy].
This study assesses the usefulness of duplex sonography in the diagnosis of oesophageal varices. 32 patients with liver cirrhosis were studied by endoscopy and duplex sonography. There was an excellent correlation in the case of the medium-sized and large-sized varices. Only small varices could not be detected by duplex sonography. On the other hand, 3 large-sized paraoesophageal varices, which were not identified by endoscopy, were easily seen by duplex sonography. The sensitivity of duplex sonography was between 0.8 and 0.9, the accuracy between 0.93 and 0.96.


A nebulin ruler does not dictate thin filament lengths.
To generate force, striated muscle requires overlap between uniform-length actin and myosin filaments. The hypothesis that a nebulin ruler mechanism specifies thin filament lengths by targeting where tropomodulin (Tmod) caps the slow-growing, pointed end has not been rigorously tested. Using fluorescent microscopy and quantitative image analysis, we found that nebulin extended 1.01-1.03 mum from the Z-line, but Tmod localized 1.13-1.31 mum from the Z-line, in seven different rabbit skeletal muscles. Because nebulin does not extend to the thin filament pointed ends, it can neither target Tmod capping nor specify thin filament lengths. We found instead a strong correspondence between thin filament lengths and titin isoform sizes for each muscle. Our results suggest the existence of a mechanism whereby nebulin specifies the minimum thin filament length and sarcomere length regulates and coordinates pointed-end dynamics to maintain the relative overlap of the thin and thick filaments during myofibril assembly.


Multi-scale genetic dynamic modelling I : an algorithm to compute generators.
We present a new approach or framework to model dynamic regulatory genetic activity. The framework is using a multi-scale analysis based upon generic assumptions on the relative time scales attached to the different transitions of molecular states defining the genetic system. At micro-level such systems are regulated by the interaction of two kinds of molecular players: macro-molecules like DNA or polymerases, and smaller molecules acting as transcription factors. The proposed genetic model then represents the larger less abundant molecules with a finite discrete state space, for example describing different conformations of these molecules. This is in contrast to the representations of the transcription factors which are-like in classical reaction kinetics-represented by their particle number only. We illustrate the method by considering the genetic activity associated to certain configurations of interacting genes that are fundamental to modelling (synthetic) genetic clocks. A largely unknown question is how different molecular details incorporated via this more realistic modelling approach lead to different macroscopic regulatory genetic models which dynamical behaviour might-in general-be different for different model choices. The theory will be applied to a real synthetic clock in a second accompanying article (Kirkilioniset al., Theory Biosci, 2011).


Characterising switching behaviour in perceptual multi-stability.
When people experience an unchanging sensory input for a long period of time, their perception tends to switch stochastically and unavoidably between alternative interpretations of the sensation; a phenomenon known as perceptual bi-stability or multi-stability. The huge variability in the experimental data obtained in such paradigms makes it difficult to distinguish typical patterns of behaviour, or to identify differences between switching patterns. Here we propose a new approach to characterising switching behaviour based upon the extraction of transition matrices from the data, which provide a compact representation that is well-understood mathematically. On the basis of this representation we can characterise patterns of perceptual switching, visualise and simulate typical switching patterns, and calculate the likelihood of observing a particular switching pattern. The proposed method can support comparisons between different observers, experimental conditions and even experiments. We demonstrate the insights offered by this approach using examples from our experiments investigating multi-stability in auditory streaming. However, the methodology is generic and thus widely applicable in studies of multi-stability in any domain.


A new approach for evaluation of left ventricular diastolic function: spatial and temporal analysis of left ventricular filling flow propagation by color M-mode Doppler echocardiography.
To evaluate left ventricular diastolic function and differentiate the pseudonormalized transmitral flow pattern from the normal pattern, the propagation of left ventricular early filling flow was assessed quantitatively using color M-mode Doppler echocardiography. Because the propagation of left ventricular early filling flow is disturbed in the left ventricle with impaired relaxation, quantification of such alterations should provide useful indexes for the evaluation of left ventricular diastolic function. Study subjects were classified into three groups according to the ratio of early to late transmitral flow velocity (E/A ratio) and left ventricular ejection fraction: 29 subjects with an ejection fraction > or = 60% (control group); 34 with an ejection fraction < 60% and E/A ratio < 1 (group I); and 25 with ejection fraction < 60% and E/A ratio > or = 1 (group II). The propagation of peak early filling flow was visualized by changing the first aliasing limit of the color Doppler signals. The rate of propagation of peak early filling flow velocity was defined as the distance/time ratio between two sampling points: the point of the maximal velocity around the mitral orifice and the point in the mid-left ventricle at which the velocity decreased to 70% of its initial value. High fidelity manometer-tipped measurement was performed in 40 randomly selected subjects. The rate of propagation decreased in groups I and II compared with that in the control group (33.8 +/- 13.8 [mean +/- SD] and 30.0 +/- 8.6 vs. 74.3 +/- 17.4 cm/s, p < 0.001, respectively) and correlated inversely with the time constant of left ventricular isovolumetric relaxation and the minimal first derivative of left ventricular pressure (peak negative dP/dt) (r = 0.82 and r = 0.72, respectively). Spatial and temporal analysis of filling flow propagation by color M-mode Doppler echocardiography was free of pseudonormalization and correlated well with the invasive variables of left ventricular relaxation.


Systolic anterior motion of the mitral valve after mitral valve repair without a ring.
We report a case of systolic anterior motion of the mitral valve after mitral reconstruction without a semirigid mitral annular ring. A 56-year-old man with mitral regurgitation due to ruptured chordae tendineae underwent mitral valve reconstruction by replacement of chordae tendineae, leaflet excision, and suture annuloplasty without an annular ring. Postoperatively, left ventricular outflow tract obstruction developed and echocardiography revealed systolic anterior motion of the mitral valve. These findings disappeared after medication with a beta-blocking drug.


Nuclear magnetic resonance imaging in Marfan's syndrome.
Detection and evaluation of aortic root and other cardiovascular abnormalities in patients with Marfan's syndrome are important in determining appropriate therapy and preventing premature mortality. To evaluate the role of nuclear magnetic resonance imaging (NMR) in this syndrome, 10 patients were evaluated using a 0.35 tesla commercial nuclear magnetic resonance imaging system. Findings from these studies were compared with data from other noninvasive tests as well as surgical follow-up. Results from these examinations indicate that NMR-derived measurements of aortic root diameter agree closely with echocardiographic measurements. In addition, NMR provides more complete anatomic detail than does echocardiography and can be utilized to assess and follow up virtually all patients with this syndrome.


Neutron activation based gamma scintigraphic evaluation of enteric-coated capsules for local treatment in colon.
The fate of two colon-specific formulations developed in our previous study was investigated using a gamma scintigraphic imaging method. The formulations contained paracetamol and samarium oxide (Sm2O3) and either microcrystalline cellulose (MCC) or hypromellose (HPMC K4M) as diluent and were coated with Eudragit S polymer. The gamma scintigraphic evaluation proved that the products remained intact in the stomach and the upper gastrointestinal tract. The gastric residence time was less that 1h. Three to four hours after administration the formulations had reached the ileo-caecal junction, i.e. the small intestine transit time was approximately 3h. The capsules disintegrated in the ileo-caecal junction or in the ascending colon. The capsules containing MCC released the marker momentarily, the capsules containing HPMC K4M gradually spreading it to the whole colon. The gamma images also verified that the HPMC gel disintegrates completely in 12-14 h. While comparing the results to those previously obtained from the bioavailability studies it could be concluded that it is possible to develop colon specific drug products that begin releasing the drug in the ileo-caecal junction or at the beginning of the ascending colon and spread the drug dose to a larger surface area by using enteric coats and hydrophilic polymers.


Interfractional variability of respiration-induced esophageal tumor motion quantified using fiducial markers and four-dimensional cone-beam computed tomography.
To investigate the interfractional variability of respiration-induced esophageal tumor motion using fiducial markers and four-dimensional cone-beam computed tomography (4D-CBCT) and assess if a 4D-CT is sufficient for predicting the motion during the treatment. Twenty-four patients with 63 markers visible in the retrospectively reconstructed 4D-CBCTs were included. For each marker, we calculated the amplitude and trajectory of the respiration-induced motion. Possible time trends of the amplitude over the treatment course and the interfractional variability of amplitudes and trajectory shapes were assessed. Further, the amplitudes measured in the 4D-CT were compared to those in the 4D-CBCTs. The amplitude was largest in the cranial-caudal direction of the distal esophagus (mean: 7.1mm) and proximal stomach (mean: 7.8mm). No time trend was observed in the amplitude over the treatment course. The interfractional variability of amplitudes and trajectory shapes was limited (mean: ≤1.4mm). Moreover, small and insignificant deviation was found between the amplitudes quantified in the 4D-CT and in the 4D-CBCT (mean absolute difference: ≤1.0mm). The limited interfractional variability of amplitudes and trajectory shapes and small amplitude difference between 4D-CT-based and 4D-CBCT-based measurements imply that a single 4D-CT would be sufficient for predicting the respiration-induced esophageal tumor motion during the treatment course.


Cost and clinical outcomes of postoperative intensive care unit versus general floor management in head and neck free flap reconstructive surgery patients.
To compare clinical, surgical, and cost outcomes in patients undergoing head and neck free-flap reconstructive surgery in the setting of postoperative intensive care unit (ICU) against general floor management. Retrospective analysis of head and neck free-flap reconstructive surgery patients at a single tertiary academic medical center. Clinical data was obtained from medical records. Cost data was obtained via the Mayo Clinic Rochester Cost Data Warehouse, which assigns Medicare reimbursement rates to all professional billed services. A total of 502 patients were included, with 82 managed postoperatively in the ICU and 420 on the general floor. Major postoperative outcomes did not differ significantly between groups (Odds Ratio[OR] 1.54; p = 0.41). After covariate adjustments, patients managed in the ICU had a 3.29 day increased average length of hospital stay (Standard Error 0.71; p < 0.0001) and increased need for take-back surgery (OR 2.35; p = 0.02) when compared to the general floor. No significant differences were noted between groups in terms of early free-flap complications (OR 1.38;p = 0.35) or late free-flap complications (Hazard Ratio 0.81; p = 0.61). Short-term cost was $8772 higher in the ICU (range = $5640-$11,903; p < 0.01). Long-term cost did not differ significantly. Postoperative management of head and neck oncologic free-flap patients in the ICU does not significantly improve major postoperative outcomes or free-flap complications when compared to general floor care, but does increase short-term costs. General floor management may be appropriate when cardiopulmonary compromise is not present.


Spontaneous reporting of hepatotoxicity associated with antiandrogens: data from the Spanish pharmacovigilance system.
To analyse the type and main features of the hepatotoxicity induced by steroidal and non-steroidal antiandrogens spontaneously reported by physicians, pharmacists and nurses. This analysis could increase the information related to these adverse reactions mainly available from the published isolated cases. Using the Spanish Pharmacovigilance database we searched for spontaneous reports recorded since the date of approval of each antiandrogen up to the present time. We analysed the frequency of liver disorders, the preferred terms coded, the presence of other hepatotoxic drugs, and the characteristics of cases of hepatitis. Liver disorders were the most common adverse reactions associated with flutamide and bicalutamide, but not with cyproterone acetate. 'Hepatitis' and 'cholestatic hepatitis' were the most frequent terms coded. In 38% of the reports related to cyproterone acetate, 18% of those related to flutamide and 33% of those related to bicalutamide the patient had simultaneously received other hepatotoxic drugs. The disproportionality analysis of hepatitis showed a strong association with flutamide and a weak association with bicalutamide and cyproterone acetate. Mean doses of flutamide and bicalutamide were very close to their defined daily dose (DDD) to treat prostate cancer, although in the case of cyproterone acetate it was slightly higher. The latency period of hepatitis was between 3 and 10 months for the three antiandrogens, and the recovery period was shorter (0.5-3 months). The majority of the reported cases of hepatitis evolved favourably. Our results highlight the hepatotoxic potential of flutamide compared to cyproterone acetate. The data related to bicalutamide should be cautiously considered due to the smaller number of reports.


Linezolid reduces length of stay and duration of intravenous treatment compared with vancomycin for complicated skin and soft tissue infections due to suspected or proven methicillin-resistant Staphylococcus aureus (MRSA).
We compared the health outcomes in patients treated with linezolid or vancomycin for complicated skin and soft tissue infections (cSSTIs). This analysis is part of a randomised, open-label, multinational trial involving 1200 adult patients hospitalised with cSSTIs due to suspected or proven methicillin-resistant Staphylococcus aureus (MRSA). Subjects received linezolid 600 mg intravenous (i.v.) or oral, or vancomycin 1g i.v. every 12 h. A test-of-cure was assessed at 7 days post therapy. Compared with vancomycin, linezolid treatment was associated with significantly shorter length of stay (all P < 0.01), decreased i.v. antibiotic treatment duration (all P < 0.0001) and higher discharge rates (all P < 0.05). Thus, linezolid has the potential to reduce medical resource use for the treatment of cSSTIs.


Ascending projections of the posterior nucleus of the hypothalamus: PHA-L analysis in the rat.
With the exception of a report by R.B. Veazey, D.G. Amaral, and W.M. Cowan (1982, J. Comp. Neurol. 207:135-156) that examined the projections of the posterior hypothalamic area in the monkey by using the autoradiographic technique, the ascending projections of the posterior nucleus (PH) of the hypothalamus have not been systematically examined in any species. The present report describes the ascending projections of PH in the rat by using the anterograde anatomical tracer, Phaseolus vulgaris-leucoagglutinin (PHA-L). The major ascending route for PH fibers is the medial forebrain bundle. PH fibers project densely to several subcortical and cortical sites. The subcortical sites are the subthalamus/hypothalamus (zona incerta, the supramammillary nucleus, lateral, perifornical, dorsal, and anterior nuclei/areas), the thalamus (lateroposterior, laterodorsal, parafascicular, reuniens, paraventricular, central medial, paracentral, central lateral and intermediodorsal nuclei), the amygdala (central, lateral, and medial nuclei), the septal area (bed nucleus of stria terminalis, medial and lateral septum), and the basal forebrain (horizontal/vertical limbs of diagonal band nuclei and lateral preoptic area). The cortical sites are the perirhinal, insular, frontal (lateral agranular), prelimbic, and infralimbic cortices. The diversity of PH projections to subcortical and cortical "limbic-related" sites and to several structures with direct input to the hippocampus (supramammillary nucleus, reuniens, paraventricular and laterodorsal nuclei of the thalamus, medial and lateral septum, and perirhinal cortex) suggest that the PH may serve a critical role in various components of emotional behavior, including mnemonic processes associated with significant emotional events.


Using deep-sea images to examine ecosystem services associated with methane seeps.
Deep-sea images are routinely collected during at-sea expeditions and represent a repository of under-utilized knowledge. We leveraged dive videos collected by the remotely-operated vehicle Hercules (deployed from E/V Nautilus, operated by the Ocean Exploration Trust), and adapted biological trait analysis, to develop an approach that characterizes ecosystem services. Specifically, fisheries and climate-regulating services related to carbon are assessed for three southern California methane seeps: Point Dume (∼725 m), Palos Verdes (∼506 m), and Del Mar (∼1023 m). Our results enable qualitative intra-site comparisons that suggest seep activity influences ecosystem services differentially among sites, and site-to-site comparisons that suggest the Del Mar site provides the highest relative contributions to fisheries and carbon services. This study represents a first step towards ecosystem services characterization and quantification using deep-sea images. The results presented herein are foundational, and continued development should help guide research and management priorities by identifying potential sources of ecosystem services.


Bacterial target-specific photocatalyst for the enhancement of antibacterial property to targets.
A bacterial target-specific titanium oxide (TiO2) photocatalyst was developed for the enhancement of selective inactivation of targeted bacteria. An antibacterial composition comprising TiO2 particles immobilized with a bacterial-specific antibody having affinity to bacteria of interest was prepared via a carbodiimide hydrochloride/N-hydroxysulfosuccinimide (EDC/NHS) coupling reaction between polyacrylic acid (PAA) coated TiO2 and an antibody. As a model case, an antibody to Escherichia coli was conjugated with the PAA-coated TiO2 (TiO2-AbE). We evaluated the enhancement of the antibacterial effect of TiO2-AbE against target E. coli, compared with its effect on other bacteria that lack affinity for the antibody used. The TiO2-AbE inactivated approximately 90% of the E. coli at 15 min, whereas the raw TiO2 inactivated approximately 20% of the E. coli after the same period of time under UV irradiation. The TiO2-AbE did not show an enhanced antibacterial effect against non-target bacteria. We infer that close contact between TiO2 particles and E. coli, as a result of the specificity of the antibody, can enhance the direct transfer of reactive oxygen species (ROS) generated by TiO2 particles to the cellular surface under UV irradiation and result in rapid and efficient inactivation of the targeted bacteria. The strategy presented here will facilitate the combination of other receptors and TiO2 particles for the preparation of highly selective and photocatalytic composites to prevent or remediate contamination by unwanted bacteria in a wide variety of natural and man-made systems.


Psoriasis without neutrophils.
Histologic studies suggest that polymorphonuclear leukocytes (polys) may initiate, enable, and/or enhance the development of psoriasis. A man with long-standing psoriasis developed acute myelogenous leukemia. His psoriasis disappeared after treatment with daunorubicin and cytosine arabinoside. Smears of his peripheral blood showed essentially zero polys from day 10 to day 22 after start of chemotherapy. His psoriasis began to reappear on day 14, became prominent by day 16, and persisted. Polys may not be requisite for the development and maintenance of psoriasis.


The Embodiment of an Older Avatar in a Virtual Reality Setting Impacts the Social Motivation of Young Adults.
Socio-emotional selectivity theory implies that an individual's motives change over their lifespan, starting with a focus on information seeking and shifting toward the motivation of maintaining emotionally meaningful social relationships in old age. The concept of future time perspective serves as an underlying mechanism for this phenomenon. This study aimed to capture how social motivation changes as a result of the manipulation of one's own visual appearance. Thus, the explicit age stereotypes of N = 74 participants were assessed, among other covariates. The following intervention consisted of a virtual reality (VR) scenario in which the experimental group embodied an old age avatar and the control group a young age avatar. Changes in social motivation were assessed using the concept of socio-emotional selectivity based on imagined situational preferences. Results with strong effect sizes indicate that changes in social motivation commonly connected with old age might be caused by visual cues when actively embodying a virtual avatar.


Association between maternal exposure to particulate matter (PM2.5) and adverse pregnancy outcomes in Lima, Peru.
The literature shows associations between maternal exposures to PM2.5 and adverse pregnancy outcomes. There are few data from Latin America. We have examined PM2.5 and pregnancy outcomes in Lima. The study included 123,034 births from 2012 to 2016, at three public hospitals. We used estimated daily PM2.5 from a newly created model developed using ground measurements, satellite data, and a chemical transport model. Exposure was assigned based on district of residence (n = 39). Linear and logistic regression analyzes were used to estimate the associations between air pollution exposure and pregnancy outcomes. Increased exposure to PM2.5 during the entire pregnancy and in the first trimester was inversely associated with birth weight. We found a decrease of 8.13 g (-14.0; -1.84) overall and 18.6 g (-24.4, -12.8) in the first trimester, for an interquartile range (IQR) increase (9.2 µg/m3) in PM2.5. PM2.5 exposure was positively associated with low birth weight at term (TLBW) during entire pregnancy (OR: 1.11; 95% CI: 1.03-1.20), and at the first (OR: 1.11; 95% CI: 1.03-1.20), second (OR: 1.09; 95% CI: 1.01-1.17), and third trimester (OR: 1.10; 95% CI: 1.02-1.18) per IQR (9.2 µg/m3) increase. Higher exposure to PM2.5 was also associated with increased risk of small for gestational age (SGA). There were no statistically significant associations between PM2.5 exposure and preterm births (PTB). Exposure to higher concentrations of PM2.5 in Lima may decrease birth weight and increase the frequency of TLBW and SGA. Our study was inconsistent with the literature in finding no associations with preterm birth.


Occurrence of deletion plasmids at high rates after conjugative transfer of the plasmids RP4 and RK2 from Escherichia coli to Alcaligenes eutrophus H16.
The broad host-range IncP-1 plasmids RP4 and RK2 were transferred by conjugation from Escherichia coli to Alcaligenes eutrophus H16. Among the transconjugants selected on media containing tetracycline, a considerable number did not express kanamycin resistance. By comparing restriction patterns of plasmids isolated from a large number of transconjugants a variety of different deletion derivatives were found. All of these possess more or less extended deletions always including parts of the tra 1-region. The plasmids RP4 and RK2, once established in A. eutrophus H16 showed a high stability and it can be concluded that deletion formation is connected with the conjugation process. Evidence is given that degradation of DNA entering an A. eutrophus recipient cell during the conjugative transfer process may be involved in deletion formation. Furthermore, the finding of a small deletion derivative of RP4 lacking the transacting replication function trfB and the entire kil-kor-system may allow the assumption that these gene functions are not essential for replication and maintenance of RP4 in A. eutrophus hosts.


Pathologic effects of antimetabolites on the hippocampus of diet controlled mice.
Marked histological changes are observed in the hippocampi of mice maintained on a niacin deficient diet following a single injection of 3-acetylpyridine (antimetabolite of nicatinamide). Extensive neuronal damage occurs in areas H2, H3 and to a lesser degree in the dentate gyrus. The neurons appear to be shrunken, deeply basophilic and exhibit a loss of intracellular architecture. The neuronal response in pyridoxine deficient mice treated with 4-methoxypyridoxine (antimetabolite of pyridoxine) is not remarkable.


Electron microscopic and immunocytochemical study of rapidly frozen, freeze-substituted neural lobes of rats.
Rapid freezing of freshly dissected or incubated neural lobes was explored as a means of obtaining ultrastructural preservation of the more natural state of this tissue. A quantitative assessment of the region of good fixation was made in order to determine the relative fractions occupied by axons, pituicytes and the extracellular space. The immunocytochemical distributions of neurophysins and the glycopeptide portion of the vasopressin precursor were evaluated using the immunogold technique in order to determine the relative numbers of oxytocin and vasopressin fibre types in the fixed region, and the subcellular localization of these antigens. The uncut surface of rat neural lobes was rapidly frozen against a highly polished copper plug and freeze-substituted in osmium-acetone either immediately after dissection (approximately 2 min), or after a 15 min incubation period in vitro in an oxygenated, balanced salt solution. Substituted neural lobes were prepared for either conventional electron microscopy, or for immunogold labelling of neurophysins and the glycopeptide precursor to vasopressin. Membranes, subcellular organelles and extracellular matrix were well preserved 10 microns deep to the contacted surface. The extracellular space accounted for approximately 30% of the cross-sectional area of the neuropil and could be divided into two domains: an extended perivascular space (28-29% of total area); and a narrow (approximately 24 nm; approximately 1% of total) space between closely apposed neurosecretory processes or between these processes and pituicytes. Pituicytes accounted for about 30% of the area and axons 20-25%. Pituicytes occupied close to 60% of the basal lamina at the neurohaemal contact zone, while axons occupied approximately 20%. There were no differences between neural lobes frozen immediately after dissection and those incubated for 15 min in any of these measures, suggesting minimal fluid redistribution. Gold particles were specifically localized over large (100-200 nm) dense core vesicles, and less frequently over multivesicular bodies and lysosomes. No etching of the plastic or reduction of osmium was necessary to achieve labelling. Specific labelling of one set of terminals and axons (about 80%) was observed with the monoclonal antibody previously shown to be specific for oxytocin-neurophysin, while in neighbouring sections the remaining 20% of the processes were labelled with the antiserum to the vasopressin precursor, or with non-specific antibodies to neurophysins. In conclusion, ultrarapid freezing preserves a large extracellular space in the neural lobe and provides for high resolution morphological and immunocytochemical studies of neurohypophysial structure.


Role of ion channels in ionizing radiation-induced cell death.
Neoadjuvant, adjuvant or definitive fractionated radiation therapy are implemented in first line anti-cancer treatment regimens of many tumor entities. Ionizing radiation kills the tumor cells mainly by causing double strand breaks of their DNA through formation of intermediate radicals. Survival of the tumor cells depends on both, their capacity of oxidative defense and their efficacy of DNA repair. By damaging the targeted cells, ionizing radiation triggers a plethora of stress responses. Among those is the modulation of ion channels such as Ca2+-activated K+ channels or Ca2+-permeable nonselective cation channels belonging to the super-family of transient receptor potential channels. Radiogenic activation of these channels may contribute to radiogenic cell death as well as to DNA repair, glucose fueling, radiogenic hypermigration or lowering of the oxidative stress burden. The present review article introduces these channels and summarizes our current knowledge on the mechanisms underlying radiogenic ion channel modulation. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.


Mediator lipidomics: search algorithms for eicosanoids, resolvins, and protectins.
Within the domain of lipidomics, lipid mediator lipidomics and informatics is an exciting area because of the important roles of lipid-derived mediators in health and disease. It is well-appreciated that arachidonic acid is a precursor to potent bioactive mediators, such as prostaglandins, leukotrienes, and lipoxins. Recent experiments employing a mediator-lipidomic approach have uncovered that other major essential polyunsaturated fatty acids, such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), serve as precursors for the production of potent bioactive mediator families, coined "resolvins" and "protectins." These omega-3 polyunsaturated fatty acids have long been noted to have beneficial effects in human systems; however, molecular evidence for their beneficial actions has been lacking and/or subject to debate. In this chapter, we review the databases and search algorithms used to identify these novel lipid mediators using liquid chromatography-ultraviolet-tandem mass spectrometry (LC-UV-MS/MS). Cognoscitive-contrast-angle algorithms and databases (COCAD) and systematic naming and empirical fragmentation rules useful in MS/MS ion identification were developed. Examples of identifying eicosanoids, resolvins, and protectins are given in human and murine tissues. The findings reviewed in this chapter demonstrate the advantages of COCAD in profiling and identification of bioactive lipid mediators and documenting activation of their biosynthetic pathways as well as in establishing relationships between lipid mediator pathways with agonists and antagonists present in the biological system.


Biology of human hair: know your hair to control it.
Hair can be engineered at different levels--its structure and surface--through modification of its constituent molecules, in particular proteins, but also the hair follicle (HF) can be genetically altered, in particular with the advent of siRNA-based applications. General aspects of hair biology are reviewed, as well as the most recent contributions to understanding hair pigmentation and the regulation of hair development. Focus will also be placed on the techniques developed specifically for delivering compounds of varying chemical nature to the HF, indicating methods for genetic/biochemical modulation of HF components for the treatment of hair diseases. Finally, hair fiber structure and chemical characteristics will be discussed as targets for keratin surface functionalization.


Biodegradation of petroleum hydrocarbons in an immobilized cell airlift bioreactor.
An "immobilized cell airlift bioreactor", was used for the aerobic bioremediation of simulated diesel fuel contaminated groundwater and tested with p-xylene and naphthalene in batch and continuous regimes. The innovative design of the experiments consists of two stages. At the first stage "immobilized soil bioreactor" (ISBR) was used to develop an efficient microbial consortium from the indigenous microorganisms, which exist in diesel fuel contaminated soil. The concept of ISBR relies on the entrapment of the soil particles into the pores of a semi-permeable membrane, which divides the bioreactor into two aerated and non-aerated portions. The second stage involves inoculating the "immobilized cell air lift bioreactor" with the cultivated microbial consortia of the first stage. Immobilized cell airlift bioreactor has the same configuration as ISBR except that in this bioreactor instead of soil, microorganisms were immobilized on the fibers of the membrane. The performance of a 0.83 L immobilized cell airlift bioreactor was investigated at various retention time (0.5-6 h) and concentrations of p-xylene (15, 40 and 77 mg/L) and naphthalene (8, 15 and 22 mg/L) in the continuous operation. In the batch regime, 0.9L bioreactor was operated at various biodegradation times (15-135 min) and concentrations of p-xylene (13.6, 44.9 and 67.5 mg/L) and naphthalene (1.5 and 3.8 mg/L). Under the conditions of the complete biodegradation of p-xylene and naphthalene, the obtained volumetric biodegradation rates at biomass density of 720 mg/L were 15 and 16 mg/L h, respectively.


Lotilaner Ophthalmic Solution, 0.25%, for the Treatment of Demodex Blepharitis: Results of a Prospective, Randomized, Vehicle-Controlled, Double-Masked, Pivotal Trial (Saturn-1).
The purpose of this study was to evaluate the safety and efficacy of lotilaner ophthalmic solution, 0.25%, compared with vehicle for the treatment of Demodex blepharitis. In this prospective, randomized, controlled, double-masked, phase 2b/3 clinical trial, 421 patients with Demodex blepharitis were randomly assigned in a 1:1 ratio to receive either lotilaner ophthalmic solution, 0.25% (study group), or vehicle without lotilaner (control group) bilaterally, twice daily for 43 days. Patients were evaluated at days 8, 15, 22, and 43. Outcome measures were complete collarette cure (collarette grade 0), clinically meaningful collarette cure (grade 0 or 1), mite eradication (0 mites/lash), erythema cure (grade 0), composite cure (grade 0 for collarettes/erythema), and drop comfort. Adverse events were also evaluated. At day 43, the study group achieved a statistically significantly higher proportion of patients with clinically meaningful collarette cure (81.3% vs. 23.0%; P < 0.0001), complete collarette cure (44.0% vs. 7.4%; P < 0.0001), mite eradication (67.9% vs. 17.6%; P < 0.0001), erythema cure (19.1% vs. 6.9%; P = 0.0001), and composite cure (13.9% vs. 1.0%; P < 0.0001) than the control group. Nearly 92.0% of patients rated the study drop as neutral to very comfortable. All ocular adverse events in the study group were mild, with the most common being instillation site pain. Twice-daily treatment with a novel lotilaner ophthalmic solution, 0.25% for 43 days, is safe and effective for the treatment of Demodex blepharitis compared with the vehicle control.


Histology-directed matrix-assisted laser desorption/ionization analysis reveals tissue origin and p53 status of primary liver cancers.
To date, protein profiles for hepatocellular carcinomas and cholangiocarcinomas have not been systematically evaluated and compared with each other in an unbiased way. Thirty-six hepatocellular carcinomas and adjacent normal tissue samples were analyzed using histology-directed, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS). Four cholangiocarcinomas and adjacent normal tissue samples were also evaluated. Tissue samples were sectioned at 10 µm, with 1-3 sections thaw-mounted on a conductive indium tin oxide-coated glass slide. Sinapinic acid was manually deposited on areas of each tissue section enriched by epithelial cells, either tumor or normal, and mass spectra were acquired using a MALDI-time of flight instrument. According to class prediction analysis, average prediction accuracy in test sets (composed of 18 hepatocellular carcinoma-normal pairs) ranged from 93.0 to 95.8%. Cholangiocarcinomas and hepatocellular carcinomas had different protein profiles, as evidenced by average prediction accuracy of >95% in the test set for all classifiers. Permutation P-values for 0.632 + bootstrap cross validated misclassification rates (at feature selection P < 0.001) were less than 0.05 for predicting p53 immunostaining status. We conclude that MALDI MS profiles may be useful in assisting with the diagnosis and the differential diagnosis of primary liver cancers.


[Development of the iridocorneal angle and congenital glaucoma].
The trabecular meshwork originates from cells of the neural crest which migrate to the iridocorneal angle during embryonic and fetal development of the eye. Correct morphogenesis of trabecular outflow pathways requires the differentiation of the cells to a porous and lamellate meshwork as well as the ingrowth of Schlemm's canal and posterior movement of the iris root. A failure in these processes is responsible for primary congenital or infantile glaucoma which presents with increased resistance to aqueous humor outflow resulting in increased intraocular pressure. Most cases appear to be of a sporadic nature but hereditary cases are often caused by mutations in the CYP1B1 gene which encodes for the enzyme cytochrome P450 1B1. Mutations cause a reduction in enzymatic activity which probably leads to diminished turnover of an as yet unidentified metabolite taking part in the signaling processes essential for formation of the trabecular meshwork and Schlemm's canal. More rarely, mutations in latent transforming growth factor beta binding protein 2 (LTBP2) or in the transcription factor FOXC1 have been described as causative for primary congenital glaucoma.


Do carbon emissions impact the health of residents? Considering China's industrialization and urbanization.
Industrialization and urbanization have aggravated the contradiction between environmental protection and economic growth, leading to health issues. While there are considerable interests in understanding the health effects of carbon emissions in the context of climate change, little is observed at regional scale and by econometric methods. Applying regression analysis on 2002-2017 Chinese provincial-level panel data, this study explores the intermediary mechanisms and regional differences of carbon emissions on residents' health. The results indicate that: (1) Carbon emissions have a long-term adverse impact on residents' health-a 1% rise in carbon emission adds 0.298% more outpatients and 0.162% more inpatients; (2) The rise in carbon emissions impairs residents' health mainly by raising the temperature; (3) In areas with high levels of industrialization and urbanization, increased carbon emissions bring greater health risks; and (4) In terms of China's unique "leading industrialization and lagging urbanization" situation, only by upgrading industrial structure, improving urbanization quality, and promoting coordinated industrialization and urbanization can the harm of carbon emissions to residents' health be reduced. Therefore, the "one-size-fits-all" policy model is not suitable for China's current situation. To address global "climate change" issues, China must act according to local conditions by applying mitigating (adaptive) measures in economically developed (less developed) regions. Simultaneously, the authorities must focus on the interaction and synergy between industrialization and urbanization.


Islet-like cell aggregates generated from human adipose tissue derived stem cells ameliorate experimental diabetes in mice.
Type 1 Diabetes Mellitus is caused by auto immune destruction of insulin producing beta cells in the pancreas. Currently available treatments include transplantation of isolated islets from donor pancreas to the patient. However, this method is limited by inadequate means of immuno-suppression to prevent islet rejection and importantly, limited supply of islets for transplantation. Autologous adult stem cells are now considered for cell replacement therapy in diabetes as it has the potential to generate neo-islets which are genetically part of the treated individual. Adopting methods of islet encapsulation in immuno-isolatory devices would eliminate the need for immuno-suppressants. In the present study we explore the potential of human adipose tissue derived adult stem cells (h-ASCs) to differentiate into functional islet like cell aggregates (ICAs). Our stage specific differentiation protocol permit the conversion of mesodermic h-ASCs to definitive endoderm (Hnf3β, TCF2 and Sox17) and to PDX1, Ngn3, NeuroD, Pax4 positive pancreatic endoderm which further matures in vitro to secrete insulin. These ICAs are shown to produce human C-peptide in a glucose dependent manner exhibiting in-vitro functionality. Transplantation of mature ICAs, packed in immuno-isolatory biocompatible capsules to STZ induced diabetic mice restored near normoglycemia within 3-4 weeks. The detection of human C-peptide, 1155±165 pM in blood serum of experimental mice demonstrate the efficacy of our differentiation approach. h-ASC is an ideal population of personal stem cells for cell replacement therapy, given that they are abundant, easily available and autologous in origin. Our findings present evidence that h-ASCs could be induced to differentiate into physiologically competent functional islet like cell aggregates, which may provide as a source of alternative islets for cell replacement therapy in type 1 diabetes.


Analysis of factors affecting the implementation of green human resource management using a hybrid fuzzy AHP and type-2 fuzzy DEMATEL approach.
The topic of green human resource management has attracted considerable attention during this last decade. Despite this interest, little research has been conducted to explore the successful implementation of green human resource management to achieve environmental sustainability goals. Therefore, this study aims to identify the factors affecting the effective implementation of green human resource management in petrochemical companies in Bushehr City. This research is the first article that has evaluated green human resource management measures in petrochemical industries, and on the other hand, it can be stated that it is the first paper to perform green measures of human resource management using the combined method of fuzzy hierarchical analysis and type-2 fuzzy DEMATEL. The present study seeks to identify these factors and examine their relationships based on existing theoretical foundations and expert opinions. Based on results, factors affecting green human resource management implementation were divided into five categories: recruitment and employment, training and development, performance appraisal, service compensation and reward, and green organizational culture management. In other words, a total of five criteria and twenty green sub-criteria were identified for the implementation of green human resource management. Fuzzy AHP and type-2 fuzzy DEMATEL were applied to determine the weights of the criteria. The results showed that the process of green training and development is the most critical factor in the effective implementation of green human resource management. Also, training and development processes, service compensation, and green organizational culture management are affecting factors to achieve this critical issue. In order to implement green human resource management, this study has proposed the priority of green measures for petrochemical industry managers.


Intimal cell mass-derived atherosclerotic lesions in the abdominal aorta of hyperlipidemic swine. Part 2. Investigation of endothelial cell changes and leukocyte adherence associated with early smooth muscle cell proliferative activity.
We have investigated several aspects of endothelial cell (EC) behavior during the initiation and early development of intimal cell mass (ICM)-derived atherosclerotic lesions in the distal abdominal aortas of young swine fed hyperlipidemic (HL) diets for 0, 14, 49, or 90 days. By scanning electron microscopy no breaks in endothelial integrity or other abnormalities were observed even at 90 days on diet after lesions were well established. Also, counts of leukocytes adherent to the endothelium by both scanning and light microscopy revealed no greater numbers in HL than in mash control swine. Estimates of individual EC losses over ICM-lesions in the HL swine (based on calculations from tritiated thymidine labeling indices and EC growth rates determined by counts) suggested a loss of approximately one per 100 EC/day. This loss over ICM lesion was not significantly greater than that over ICM in mash controls, but was significantly greater than that of EC not over ICM lesions in the same HL animal. In any event, the estimated loss seems to be too trivial for the endothelial barrier to be compromised even transiently in a biologically significant fashion. A significant correlation was observed between tritiated thymidine labeling indices of cells within the ICM lesions and of those of the overlying EC that was not observed with the ICM in the controls. Possibly the positive correlation may be a result of the abluminal surface of the overlying EC being exposed to the abnormal milieu of the ICM lesion. It is emphasized that results reported here apply only to ICM-derived lesions at an early stage of development and that they do not contradict results obtained by others with other lesion types such as those derived from monocytes. Furthermore, in later stages of development of ICM-derived lesions in the same model we know that extensive endothelial cell damage can be demonstrated. Also, functional changes in endothelial permeability may have been present in early stages that would not have been detected with the methods used in this study.


Gap junction formation between normal and reaggregated endoderm cells ofXenopus laevis neurulae.
Using freeze-fracture electron microscopy and fluorescent dye injection we have analysed the contacts between cells of the deeper endoderm taken from neurulae ofXenopus laevis. Endodermal cells in situ have large 1.5 μm diameter gap junctions composed of 8 nm P-face particles and corresponding E-face pits. Beside gap junctions, particle aggregates typical of desmosomal plaques are present but there are no tight junctions. The dissociation of endoderm into single cells involves profound structural alterations in the surface membrane including the complete disappearance of junctional structures among them gap junctions. The reaggregation of endoderm cells leads to the restoration of the surface membrane IMP (Intra Membrane Particle) pattern and, after ca. 30 min, to the establishment of functional pathways allowing for the intercellular transfer of fluorescent dye. Concomitantly gap junctions reappear. The observation that the dissociation and reaggregation of endodermal cells involves IMP alterations which go beyond the cell junctions themselves is discussed as an adaptation of the plasma membrane to changing environmental conditions.


The prevalence of hypertension among Malaysian adults and its associated risk factors: data from Malaysian Community Salt Study (MyCoSS).
Hypertension is one of the most common risk factors for cardiovascular disease and leading cause of mortality globally. The aims of this study were to assess the prevalence of hypertension and its associated risk factors among Malaysian population using data from the Malaysian Community Salt Study (MyCoSS). This study was a cross-sectional study using multi-stage stratified sampling method. Data collection was carried out via face-to-face interview at the respondent's home from October 2017 until March 2018. A total of 1047 respondents aged 18 years and above completed the questionnaires and blood pressure measurement. A person who reported diagnosis of hypertension by a physician and had systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg on three readings was categorised as hypertensive. Risk factors of hypertension were analysed using multiple logistic regression. The prevalence of hypertension in the present study was 49.39% (95% CI 44.27-54.51). There was no statistically significant difference in gender. Age, household income, BMI, and diabetes were significantly associated with hypertension. Hypertension found had inverse association with the level of education. Age was the strongest predictor of hypertension (35-44 years old; OR=2.39, 95% CI=1.39-4.09, 45-54 years old; OR=5.50, 95% CI=3.23-9.38, 55-64 years old OR=13.56, 95% CI=7.77-23.64 and 65 years old and above; OR=25.28, 95% CI=13.33-48.66). Those who had higher BMI more likely to be hypertensive as compared to respondents with normal weight (overweight, OR=1.84; 95% CI=1.18-2.86; obese, OR=4.29% CI=2.56-7.29). The findings showed that hypertension is prevalent among adults in Malaysia. Those with older age, higher BMI, and diabetes are more likely to have hypertension. Efforts regarding lifestyle modification and education could be important in hypertension management and prevention.


Integrated phylogeny of the human brain and pathobiology of Alzheimer's disease: A unifying hypothesis.
The disproportionate evolutionary expansion of the human cerebral cortex with reinforcement of cholinergic innervations warranted a major rise in the functional and metabolic load of the conserved basal forebrain (BF) cholinergic system. Given that acetylcholine (ACh) regulates properties of the microtubule-associated protein (MAP) tau and promotes non-amyloidogenic processing of amyloid precursor protein (APP), growing neocortex predicts higher demands for ACh, while the emerging role of BF cholinergic projections in Aβ clearance infers greater exposure of source neurons and their innervation fields to amyloid pathology. The higher exposure of evolutionary most recent cortical areas to the amyloid pathology of Alzheimer's disease (AD) with synaptic impairments and atrophy, therefore, might involve attenuated homeostatic effects of BF cholinergic projections, in addition to fall-outs of inherent processes of expanding association areas. This unifying model, thus, views amyloid pathology and loss of cholinergic cells as a quid pro quo of the allometric evolution of the human brain, which in combination with increase in life expectancy overwhelm the fine homeostatic balance and trigger the disease process.


The influence of phenobarbital overdose on aEEG recording.
Monitoring infants with amplitude integrated electroencephalography (aEEG) in neonatal units is becoming widespread. A case of a preterm infant who was monitored with aEEG due to suspected seizures is presented. The case emphasizes both the usefulness and drawback of aEEG. An erroneous diagnosis of seizure lead to phenobarbital overdose and the change of aEEG voltage and pattern assisted in a prompt diagnosis.


Genetic network analysis between Apis mellifera subspecies based on mtDNA argues the purity of specimens from North Africa, the Levant and Saudi Arabia.
This study aimed to analyze the genetic relationships between honey bee subspecies using reference specimens and recently collected specimens from different parts of the world. The purity of these specimens was discussed in light of the obtained results. The genetic networks were constructed between 21 subspecies of honey bees, Apis mellifera L.: 9 in Africa, 7 in Europe and 5 in Asia. The analysis was performed using the mtDNA of these subspecies and the Population Analysis with Reticulate Trees software. Some subspecies were represented by more than two specimens based on the available online sequences. The subspecies A. m. sahariensis from Africa showed unique characteristics and is genetically isolated than all other studied bee subspecies. Specimens collected from Saudi Arabia showed genetic relatedness to A. m. jemenitica, A. m. lamarckii, and some European subspecies, suggesting high degree of hybridization. The close genetic relationship between the Egyptian bees, A. m. lamarckii, and the Syrian bees, A. m. syriaca, were emphasized. The overall genetic network showed the presence of three distinct branches in relation to geographical locations. The high accurateness of the used analysis was confirmed by previous phylogenetic studies as well as the genetic relationships between hybrid bees of A. m. capensis and A. m. scutellata. The genetic networks showed the presence of bee subspecies from Africa in all branches including Europe and Asia. The study suggests the impurity of some specimens mostly due to the hybridization between subspecies. Specific recommendations for future conservation efforts of bees were presented in light of this study.


Photostabilization of an entomopathogenic fungus using composite clay matrices.
To provide photostabilization for entomopathogenic fungi by anionic dyes, composite matrices based on clay-biopolymer combinations were prepared. In the first step, the negative surface charge of various clays (montmorillonite, attapulgite, bentonite and kaolinite) was reversed to positive by adsorption to the polycationic biopolymer chitosan. The second step involved adsorption of the toxicologically safe anionic dyes fast green (FG) and naphthol yellow S (NYS) to the clay complexes. Compared with cytotoxic photoprotectants like berberine, palmatine and acriflavine, the anionic dyes have no adverse effects up to a concentration of 1 M. In assays using various clay-chitosan-dye matrices and UV irradiation from a lamp source, it was evident that both FG and NYS provided considerable photostabilization for conidia of the entomopathogenic fungus Aschersonia spp. that served as a model biocontrol agent. Apparently, because of the light-dispersing property, bentonite and attapulgite per se provided significant photoprotection. All clay matrices containing FG provided a substantial photostabilization effect.


Risk factors of renal involvement and significant proteinuria in Henoch-Schönlein purpura.
Risk factors of renal involvement and significant proteinuria in patients with Henoch-Schönlein purpura (HSP) were retrospectively evaluated by univariate and multivariate analyses. The analysis was performed in 134 patients with HSP. Renal involvement was found in 65 patients (49%) and 97% of the renal involvement was found within 3 months of disease onset. Moderate or severe proteinuria was recognised in 25 patients. A univariate analysis revealed that an age of more than 4 years at the onset, severe abdominal pain with gastrointestinal bleeding, persistent purpura over a month, coagulation factor XIII activity < 80%, and treatment with factor XIII concentrate were associated with developing renal involvement. A multivariate analysis showed that severe abdominal symptoms, an age of more than 4 years, and persistent purpura increased the risk of renal involvement. Risk factors of moderate or severe proteinuria were also examined. The risk factors in a univariate analysis were severe abdominal symptoms, persistent purpura, decreased factor XIII activity, treatment with steroids, and treatment with factor XIII concentrate. Of those, persistent purpura, treatment with factor XIII concentrate, and factor XIII activity < 80% were associated with significant proteinuria in a multivariate analysis. Among the patients with severe abdominal symptoms, factor XIII activity was significantly decreased in patients with significant proteinuria compared to other patients without significant proteinuria. Long-term prognosis of Henoch-Schönlein purpura is dependent on the severity of renal involvement. In those patients who have the risk factors of renal involvement, especially significant proteinuria, close attention should be paid to a urinalysis for at least 3 months from the onset of the disease.


Acrylamide content in French fries prepared in households: A pilot study in Spanish homes.
An observational cross-sectional pilot study in 73 Spanish households was conducted to evaluate the impact of consumer practices on the formation of acrylamide during the preparation of French fries from fresh potatoes applying one stage frying. 45.2% of samples presented acrylamide concentrations above the benchmark level for French fries (500 µg/kg). 6.9% of samples exceeded 2000 µg/kg and the 95th percentile was 2028 µg/kg. The median and average values were significantly higher than the EFSA report for this food category, suggesting that the total exposure to acrylamide by the population could be underestimated. In this randomised scenario of cooking practices, the content of reducing sugar and asparagine did not explain the acrylamide levels. However, the chromatic parameter a∗ of the fried potato was a powerful tool to classify the samples according to the acrylamide benchmark level regardless of the agronomical characteristics of the potato or the consumer practices.


Accuracy of an artificial neural network for detecting a regional abnormality in myocardial perfusion SPECT.
The patient-based diagnosis with an artificial neural network (ANN) has shown potential utility for the detection of coronary artery disease; however, the region-based accuracy of the detected regions has not been fully evaluated. The aim of this study was to demonstrate the accuracy of all detected regions compared with expert interpretation. A total of 109 abnormal regions including 33 regions with stress defects and 76 regions with ischemia were examined, which were derived from 21 patients who underwent myocardial perfusion SPECT within 45 days of coronary angiography. The gray and color scale images, a polar map of stress, rest and difference, and left ventricular function were displayed on the monitor to score the extent and severity of stress defect and ischemia. Two experienced nuclear medicine physicians (Observers A and B) scored the abnormality with a 4-point scale and draw abnormal regions on a polar map. The gold standard was determined by the final judgment of normal or abnormal by the consensus of two other independent expert nuclear cardiologists, and was compared with the stress defect and ischemia derived from ANN. The concordance rate of ANN to the gold standard was higher than that of two observers. Furthermore, the κ coefficient indicated moderate to substantial agreement for stress defect and slight to the fair agreement for ischemia. The area under the curve (AUC) of ANN was the highest for both stress defect and ischemia; in particular, the ANN of ischemia showed significantly higher AUC than Observer A (p = 0.005). The ANN of stress defect showed higher specificity compared with two observers, while the ANN of ischemia showed higher sensitivity. Consequently, the accuracy of ANN showed the highest in this study. The ANN-based regional diagnosis showed a high concordance rate with the gold standard and comparable or even higher than the interpretation by nuclear medicine physicians.


Distinctive clinicopathologic features associated with regressive primary CD30 positive cutaneous lymphomas: analysis of 6 cases.
A distinct group of cutaneous lymphomas has been described on the basis of CD30 antigen expression by at least 75% of the tumoral cells. When confined to the skin, these CD30 positive cutaneous lymphomas seem to be associated with a better prognosis than CD30 negative counterparts and spontaneous regression may even occur. We observed a spontaneously regressive evolution in 6 out of 9 CD30 positive primary cutaneous large cell-lymphomas diagnosed during a 5-year period. Clinicopathological data of regressive cases were analysed. The mean age of patients was 56.5 years. They were 3 males and 3 females. Skin lesions were solitary nodule or plaque measuring from 1.5 cm to 11 cm in diameter. Histologically, the lesions were classified as pleomorphic, medium and large cell (5 cases) or large cell anaplastic lymphoma (1 case) according to the updated Kiel classification. Delay for spontaneous regression varied from 1 to 6 months. Three of the 6 patients had cutaneous relapses, followed by a spontaneous regression. All patients remained disease-free with an overall median follow-up of 30 months. Histologically, some distinctive signs such as epidermal pseudo-epitheliomatous hyperplasia, epidermotropism, edema, dermal vascular hyperplasia, seemed to be more frequently associated with spontaneously regressive evolution.


Urodynamic Outcomes in Children after Single and Multiple Injections for Overactive and Low Compliance Neurogenic Bladder Treated with Abobotulinum Toxin A.
Intradetrusor botulinum toxin is an established part of the treatment pathway for pediatric patients with neurogenic bladder. We determined the urodynamic effect of single and multiple administrations of abobotulinum toxin A in pediatric patients with neurogenic bladder, and determined the urodynamic efficacy of abobotulinum toxin A in low compliance vs overactive bladders. We conducted a single center retrospective review of all pediatric patients with neurogenic bladder treated with abobotulinum toxin A. Videourodynamic data on cystometric capacity, maximum neurogenic detrusor overactivity pressure and compliance were gathered before and after the first abobotulinum toxin A administration and after the last administration. Patients were divided into low compliance and overactive bladder groups depending on initial videourodynamics findings. Paired t-test was used to compare videourodynamic outcomes before vs after abobotulinum toxin A injection. The Mann-Whitney U test was used to compare bladder groups. A total of 30 patients were included in the study. Of these patients 15 (50%) received multiple abobotulinum toxin A injections. There were 16 patients (53%) with overactive bladder. Abobotulinum toxin A administration significantly improved cystometric capacity (p <0.0001) and maximum neurogenic detrusor overactivity (p=0.0001). Overall, compliance did not change significantly (p=0.25). There was no significant difference in urodynamic parameters between first and last abobotulinum toxin A injections. Improvement in cystometric capacity (p=0.05) and maximum neurogenic detrusor overactivity (p=0.25) was similar between the low compliance and overactive bladder groups. Compliance significantly improved in the low compliance group vs the overactive bladder group (p=0.016). Intradetrusor abobotulinum toxin A improves cystometric capacity and maximum neurogenic detrusor overactivity in pediatric patients with neurogenic bladder. This effect is maintained over multiple injections. Compliance is significantly improved in patients with low compliance bladder vs overactive bladder.