Quantum-Classical Protocol for Efficient Characterization of Absorption Lineshape and Fluorescence Quenching upon Aggregation: The Case of Zinc Phthalocyanine Dyes.
A quantum-classical protocol that incorporates Jahn-Teller vibronic coupling effects and cluster analysis of molecular dynamics simulations is reported, providing a tool for simulations of absorption spectra and ultrafast nonadiabatic dynamics in large molecular photosystems undergoing aggregation in solution. Employing zinc phthalocyanine dyes as target systems, we demonstrated that the proposed protocol provided fundamental information on vibronic, electronic couplings and thermal dynamical effects that mostly contribute to the absorption spectra lineshape and the fluorescence quenching processes upon dye aggregation. Decomposing the various effects arising upon dimer formation, the structure-property relations associated with their optical responses have been deciphered at atomistic resolution.


Psychology and the economics of invention.
Invention is an investment in which the costs of the Research and Development (R&D) project balance future returns. Those returns depend on objective factors like wage and capital costs but also on subjective factors because they are future projections. The more optimistic the inventor, the higher are the projected returns. Baumard uses Life History Theory (LHT) to relate optimism to the affluence of inventors and their societies.


Methylated tetra-amide derivatives of paramagnetic complexes for magnetic resonance biosensing with both BIRDS and CEST.
Paramagnetic agents that utilize two mechanisms to provide physiological information by magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI) are described. MRI with chemical exchange saturation transfer (CEST) takes advantage of the agent's exchangeable protons (e.g., -OH or -NHx , where 2 ≥ x ≥ 1) to create pH contrast. The agent's incorporation of non-exchangeable protons (e.g., -CHy , where 3 ≥ y ≥ 1) makes it possible to map tissue temperature and/or pH using an MRSI method called biosensor imaging of redundant deviation in shifts (BIRDS). Hybrid probes based upon 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate chelate (DOTA4- ) and its methylated analog (1,4,7,10-tetraazacyclododecane-α, α', α″, α‴-tetramethyl-1,4,7,10-tetraacetate, DOTMA4- ) were synthesized, and modified to create new tetra-amide chelates. Addition of several methyl groups per pendent arm of the symmetrical chelates, positioned proximally and distally to thulium ions (Tm3+ ), gave rise to favorable BIRDS properties (i.e., high signal-to-noise ratio (SNR) from non-exchangeable methyl proton peaks) and CEST responsiveness (i.e., from amide exchangeable protons). Structures of the Tm3+ probes elucidate the influence of methyl group placement on sensor performance. An eight-coordinate geometry with high symmetry was observed for the complexes: Tm-L1 was based on DOTA4- , whereas Tm-L2 and Tm-L3 were based on DOTMA4- , where the latter contained an additional carboxylate at the distal end of each arm. The distance of Tm3+ from terminal methyl carbons is a key determinant for sustaining BIRDS temperature sensitivity without compromising CEST pH contrast; however, water solubility was influenced by introduction of hydrophobic methyl groups and hydrophilic carboxylate. Combined BIRDS and CEST detection of Tm-L2, which features two high-SNR methyl peaks and a strong amide CEST peak, should enable simultaneous temperature and pH measurements for high-resolution molecular imaging in vivo.


Stimulus context and motor preparation in attention-deficit/hyperactivity disorder.
To investigate (1) whether and how local stimulus context variation may modify behavioural and preparatory motor processes in children, and (2) if these effects differ between healthy children and children with attention-deficit/hyperactivity disorder (ADHD) aged 9-12 years. Behavioural parameters and contingent negative variation (CNV) at cortical motor electrodes were recorded during a cued continuous performance task (AX-CPT) in three stimulus context conditions (Go, NoGo, neutral). Stimulus context was varied on the basis of stimulus types preceding the cue letter A. In all children, responses were slowed in both the NoGo- and Go-conditions relative to the neutral condition. Stimulus context affected preparatory motor processes in both groups but differentially. ADHD children showed smaller CNV potentials and a functionally irrelevant over-activation of the ipsilateral motor area. Local stimulus context may modify behavioural and preparatory motor processes in children. In ADHD, local context variations may disrupt behaviour due to inefficient regulation of supervisory higher control systems.


An insight into the electro-chemical properties of halogen (F, Cl and Br) doped BP and BN nanocages as anodes in metal-ion batteries.
Here, electro-chemical properties of BN and BP nanocages as anodes in metal-ion batteries are examined. The effect of halogens adoption of BN and BP-NCs on electro-chemical properties of M-IBs are investigated. Results showed that the BP nanocages as anode electrode in M-IBs has higher efficiency than BN nanocages and the K-IB has higher cell voltage than N-IBs. Results indicated that the halogens adoption of BN and BP-NCs are improved the cell voltage of M-IBs. Results proved that the F-doped M-IBs have higher cell voltage than M-IBs. Finally, F-B17P18 as anodes in K-IB is proposed as suitable electrodes.


Hyperinsulinemia Influences the Short-Term Efficiency of Laparoscopic Sleeve Gastrectomy for Patients with Obesity and Insulin Resistance.
The effect of hyperinsulinemia on short-term outcomes after laparoscopic sleeve gastrectomy (LSG) in patients with obesity combined with insulin resistance is unclear. This was a retrospective analysis of patients who underwent LSG at our center between January 1, 2020, and December 31, 2021. Patients were divided into hyperinsulinemia (HINS) and nonhyperinsulinemia (NHINS) groups based on fasting insulin levels. The primary endpoint was weight change. Metabolic disease outcomes, postoperative complications, and quality of life score changes were secondary endpoints. A total of 92 patients were included in this study, with 59 in the HINS group and 33 in the NHINS group. At 6 months postoperatively, the median (P25, P75) %EWL was 76.01 (64.40, 86.99)% in the HINS group and 92.02 (86.78, 100.88)% in the NHINS group (P<0.001). The mean %TWL (SD) was 23.26 (7.14)% in the HINS group and 26.80 (6.55)% in the NHINS group (P=0.021). The remission of dyslipidemia and hypertension in the NHINS group and the HINS group were not significantly different (P>0.05 for all). The differences in QOL between groups were not statistically significant (P=0.788). In terms of postoperative complications, there was no statistically significant difference between the groups (P>0.05 for all). HINS negatively influences weight change in patients with obesity and insulin resistance, and the NHINS group had better postoperative weight loss. In terms of hypertension, dyslipidemia, and postoperative complications, there was no significant effect of HINS.


Comparative authentication of Semiliquidambar cathayensis and its substituted species via macroscopic and microscopic features.
Ban Fenghe recorded in the Quality Standard of Yao Medicine of Guangxi Zhuang Autonomous Region (Volume 1) is derived from the dried stems and leaves of Semiliquidambar cathayensis. It is usually confused with medicinal herbs from Pterospermum heterophyllum and Dendropanax dentiger. However, they are very different in chemical composition, and should not be used as the same drug. To ensure their safety and efficacy, a method based on macroscopic and microscopic characteristics was developed to distinguish them. A total of 14 batches of Ban Fenghe samples from three species were collected from different producing areas in China. The macroscopic characteristics were examined by observing external traits. The tissue structures of transverse sections of stems and leaves, the leaf epidermis, and the powder were observed microscopically. The branchlets and leaf surfaces of S. cathayensis and P. heterophyllum were hairy, especially the lower leaf surfaces of P. heterophyllum were densely covered with hairs, but those of D. dentiger were hairless. The pericyclic fibers of S. cathayensis stems were intermittently distributed in a circular shape and accompanied by stone cells, whereas those of P. heterophyllum and D. dentiger were bundled without stone cells. So stone cells and hairs were present in S. cathayensis powder, stone cells were not found in P. heterophyllum and D. dentiger powder, and hairs were not present in D. dentiger powder. The distribution sites, sizes and types of secretory tissues of these three species were also different in transverse sections of stems and leaves. Stomata on the lower epidermis of S. cathayensis leaves were paracytic, whereas those of P. heterophyllum and D. dentiger were anomocytic. Ban Fenghe drugs derived from S. cathayensis could readily be distinguished from those of P. heterophyllum and D. dentiger by macroscopic and microscopic features.


In vitro effects of low intensity direct current generated silver on eukaryotic cells.
An examination of the effects of low intensity direct current generated silver, (LIDC Ag) on several types of eukaryotic microorganisms and cell culture lines suggests that LIDC Ag has an appropriate selective toxicity for prokaryotic cells. It appears that levels of this agent could be obtained clinically that would have marked bacteriostatic activity and yet have little or no effect on mammalian cells.


Targeting CK2 in cancer: a valuable strategy or a waste of time?
CK2 is a protein kinase involved in several human diseases (ranging from neurological and cardiovascular diseases to autoimmune disorders, diabetes, and infections, including COVID-19), but its best-known implications are in cancer, where it is considered a pharmacological target. Several CK2 inhibitors are available and clinical trials are underway in different cancer types. Recently, the suitability of CK2 as a broad anticancer target has been questioned by the finding that a newly developed compound, named SGC-CK2-1, which is more selective than any other known CK2 inhibitor, is poorly effective in reducing cell growth in different cancer lines, prompting the conclusion that the anticancer efficacy of CX-4945, the commonly used clinical-grade CK2 inhibitor, is to be attributed to its off-target effects. Here we perform a detailed scrutiny of published studies on CK2 targeting and a more in-depth analysis of the available data on SGC-CK2-1 vs. CX-4945 efficacy, providing a different perspective about the actual reliance of cancer cells on CK2. Collectively taken, our arguments would indicate that the pretended dispensability of CK2 in cancer is far from having been proved and warn against premature conclusions, which could discourage ongoing investigations on a potentially valuable drug target.


Hazard assessment of commonly used agricultural antibiotics on aquatic ecosystems.
In this study, eleven commonly used antibiotics including sulfonamides, tetracyclines, aminoglycosides, fluoroquinolones, and beta-lactams were evaluated for their acute and chronic aquatic toxicities using standard test organisms e.g., Vibrio fischeri, Daphnia magna, Moina macrocopa, and Oryzias latipes. Among the antibiotics tested for acute toxicity, neomycin was most toxic followed by trimethoprim, sulfamethoxazole and enrofloxacin. Sulfamethazine, oxytetracycline, chlortetracycline, sulfadimethoxine and sulfathiazole were of intermediate toxicity, while ampicillin and amoxicillin were least toxic to the test organisms. There were no trends in sensitivity among test organisms or among different classes of the antibiotics. Only the beta-lactam class was the least toxic. In chronic toxicity test, neomycin affected reproduction and adult survival of D. magna and M. macrocopa with low mg/l levels exposure. Predicted no effect concentrations (PNECs) were derived from the acute and chronic toxicity information gleaned from this study and from literature. When the PNECs were compared with measured environmental concentrations (MECs) reported elsewhere for the test compounds, hazard quotients for sulfamethoxazole, sulfathiazole, chlortetracycline, oxytetracycline, and amoxicillin exceeded unity, which suggests potential ecological implication. Therefore, further studies including monitoring and detailed toxicological studies are required to assess potential ecological risk of these frequently used veterinary antibiotics.


Lay Health Workers Engaging Latino Fathers: A qualitative study.
Behavioral Parent Training programs (BPTs) are evidence-based interventions that have been shown to be effective when implemented in various contexts and with different racial/ethnic minority families. Despite evidence showing their effectiveness within the Latinx community, disparities in access to BPTs still persist. In addition, fathers continue to show low rates of attendance and engagement despite evidence suggesting positive outcomes for the youth and family when fathers are involved in BPT treatment. Lay health workers (LHWs), community members without specialized metal health training that often live in the communities they serve, have been identified as engagement specialists that are uniquely positioned to reduce racial/ethnic disparities in access to services. The current study utilized a qualitative approach to examine this workforce's perspectives on engaging Latino fathers in parenting services in children's mental health. Qualitative themes revealed that LHWs have generally positive attitudes towards engaging Latino fathers in parenting interventions (i.e., benefits to parent-child relationship) despite experiencing barriers to engagement (e.g., culturally defined gender roles, fathers being less likely to ask for help). Themes also elucidate various engagement strategies that LHWs use to engage fathers in treatment (e.g., adapting treatment setting). Considerations for future LHW trainings and workforce development are discussed with a focus on how to incorporate cultural values in the use of father-engagement strategies.


Genome-Wide Identification and Characterization of Melon bHLH Transcription Factors in Regulation of Fruit Development.
The basic helix-loop-helix (bHLH) transcription factor family is one of the largest transcription factor families in plants and plays crucial roles in plant development. Melon is an important horticultural plant as well as an attractive model plant for studying fruit ripening. However, the bHLH gene family of melon has not yet been identified, and its functions in fruit growth and ripening are seldom researched. In this study, 118 bHLH genes were identified in the melon genome. These CmbHLH genes were unevenly distributed on chromosomes 1 to 12, and five CmbHLHs were tandem repeat on chromosomes 4 and 8. There were 13 intron distribution patterns among the CmbHLH genes. Phylogenetic analysis illustrated that these CmbHLHs could be classified into 16 subfamilies. Expression patterns of the CmbHLH genes were studied using transcriptome data. Tissue specific expression of the CmbHLH32 gene was analysed by quantitative RT-PCR. The results showed that the CmbHLH32 gene was highly expressed in female flower and early developmental stage fruit. Transgenic melon lines overexpressing CmbHLH32 were generated, and overexpression of CmbHLH32 resulted in early fruit ripening compared to wild type. The CmbHLH transcription factor family was identified and analysed for the first time in melon, and overexpression of CmbHLH32 affected the ripening time of melon fruit. These findings laid a foundation for further study on the role of bHLH family members in the growth and development of melon.


Isolation of an inhibitor of actin polymerization from human polymorphonuclear leukocytes.
A large proportion of actin in extracts of human polymorphonuclear leukocytes is unpolymerized in the presence of 0.1 M KCl, a condition expected to promote maximal assembly of purified actin. Raising of the KCl concentration increases the extent of actin polymerization in leukocyte extracts, and, at KCl concentrations greater than or equal to 0.3 M, the polymer concentration is maximal and approaches that of purified muscle actin in 0.1 M KCl solution. After removal of the actin polymers from leukocyte extracts made 0.6 M in KCl, the supernatant fluid contains an activity which inhibits the extent of assembly of purified skeletal muscle actin in 0.1 M KCl solution. We have purified this activity by ion exchange and gel filtration chromatography. The purified inhibitor contains polypeptides of 65,000 and 62,000 daltons in a molar ratio of 1:2 as determined by polyacrylamide gel electrophoresis in dodecyl sulfate. The Stokes radius of 32 A, and S20,w of 4.8 of the native inhibitor suggest that the purified protein is a mixture of monomers of slightly different molecular weight. Substoichiometric concentrations of the inhibitor rapidly prevent the assembly of purified actin in 0.1 m KCl solution in a concentration-dependent manner, and the reduction in final viscosity remains constant over time. Raising the KCl concentration reverses the inhibition, as observed for actin polymerization in unfractionated extracts. The findings are consistent with the conclusion that this inhibitor protein is responsible for the large proportion of unpolymerized actin in extracts of polymorphonuclear leukocytes.


Patient response to temporomandibular joint arthroscopy: preliminary findings in 24 patients.
A group of 24 patients who underwent TMJ arthroscopy with lysis of adhesions and lavage of 28 joints were evaluated for changes in symptoms and mandibular opening. The mean follow-up period was 7.5 months. The results revealed a general improvement in pain, joint noise, and hypomobility following TMJ arthroscopy. Measurement of mandibular opening revealed a mean increase of 5.9 mm. These results suggest that TMJ arthroscopy appears to be an excellent modality for the palliation of symptoms of TMJ pain, joint noise, and hypomobility.


Colitis-Associated Colorectal Cancer Survival is Comparable to Sporadic Cases after Surgery: a Matched-Pair Analysis.
Inflammatory bowel disease (IBD) confers an increased lifetime risk of colorectal cancer (CRC). The pathogenesis of colitis-associated CRC is considered distinct from sporadic CRC, but existing is mixed on long-term oncologic outcomes. This study aims to compare clinicopathological characteristics and survival between colitis-associated and sporadic CRC. Data was retrospectively extracted and analyzed from a single institutional database of patients with surgically resected CRC between 2004 and 2015. Patients with IBD were identified as having colitis-associated CRC. The remainder were classified as sporadic CRC. Propensity score matching was performed. Univariate and survival analyses were carried out to estimate the differences between the two groups. Of 2275 patients included in this analysis, 65 carried a diagnosis of IBD (2.9%, 33 Crohn's disease, 29 ulcerative colitis, 3 indeterminate colitis). Average age at CRC diagnosis was 62 years for colitis-associated CRC and 65 for sporadic CRC. The final propensity score matched cohort consisted of 65 colitis-associated and 130 sporadic CRC cases. Patients with colitis-associated CRC were more likely to undergo total proctocolectomy (p < 0.01) and had higher incidence of locoregional recurrence (p = 0.026) compared to sporadic CRC patients. There were no significant differences in time to recurrence, tumor grade, extramural vascular invasion, perineural invasion, or rate of R0 resections. Overall survival and disease-free survival did not differ between groups. On multiple Cox regression, IBD diagnosis was not a significant predictor of survival. Patients with colitis-associated CRC who undergo surgical resection have comparable overall and disease-free survival to patients with sporadic CRC.


Regulation of T helper type-1 immunity in hapten-induced colitis by host pretreatment with granulocyte colony-stimulating factor.
Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is an immunoregulatory drug whose effects include modulation of antigen-presentation. We investigated the potential ameliorative effect of pretreatment with rhG-CSF in a hapten-induced colitis animal model. Sprague-Dawley rats were given rhG-CSF (125 microg/kg subcutaneously twice a day for 5 days) before a colonic instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) in 50% ethanol. Consequent colonic damage was evaluated pathologically, and cytokine mRNA expression levels in macroscopically inflamed sites were measured by real-time quantitative reverse transcription-polymerase chain reaction. Pretreatment with rhG-CSF remarkably attenuated both the loss of body weight and colonic wall thickening due to progressive transmural inflammation. In the control, treatment with TNBS led to a statistically significant (p < 0.05) upregulation of IFN-gamma mRNA expression in the inflammatory sites measured at post-treatment day 7. In the experimental group, pretreatment with rhG-CSF abrogated transcription of IFN-gamma (p < 0.05), but was not, however, associated with an upregulation of IL-4 or the regulatory cytokines TGF-beta and IL-10. Furthermore, transcription of IL-12p35 (a rate-limiting factor for the production of IL-12) was significantly (p < 0.05) downregulated by rhG-CSF at 24h post-TNBS instillation, whereas IL-12p40 was not affected. Pretreatment with rhG-CSF drastically attenuated the degree of TNBS-induced colitis through selective downregulation of Th1-associated cytokines.


A patient-specific computational model of fluid-structure interaction in abdominal aortic aneurysms.
It is generally believed that knowledge of the wall stress distribution could help to find better rupture risk predictors of abdominal aortic aneurysms (AAAs). Although AAA wall stress results from combined action between blood, wall and intraluminal thrombus, previously published models for patient-specific assessment of the wall stress predominantly did not include fluid-dynamic effects. In order to facilitate the incorporation of fluid-structure interaction in the assessment of AAA wall stress, in this paper, a method for generating patient-specific hexahedral finite element meshes of the AAA lumen and wall is presented. The applicability of the meshes is illustrated by simulations of the wall stress, blood velocity distribution and wall shear stress in a characteristic AAA. The presented method yields a flexible, semi-automated approach for generating patient-specific hexahedral meshes of the AAA lumen and wall with predefined element distributions. The combined fluid/solid mesh allows for simulations of AAA blood dynamics and AAA wall mechanics and the interaction between the two. The mechanical quantities computed in these simulations need to be validated in a clinical setting, after which they could be included in clinical trials in search of risk factors for AAA rupture.


In vivo efficacy of the diuretic agent ethacrynic acid against multiple myeloma.
It was recently confirmed that the diuretic agent ethacrynic acid (EA) inhibits Wnt/beta catenin signaling in myeloma. This study investigated the antitumor effect of EA in vivo in a murine myeloma model. In vivo, tumor growth was significantly reduced and overall survival significantly prolonged in mice treated with EA as compared to untreated mice. Interestingly, this effect was higher as compared to the effect by lenalidomide, a commonly used drug against myeloma. These results reveal a significant in vivo effect by EA against myeloma.


A survey of anesthesiologists' knowledge of American Heart Association Pediatric Advanced Life Support Resuscitation Guidelines.
Determine anesthesiologists' knowledge of the 2005 American Heart Association (AHA) Pediatric Advanced Life Support (PALS) recommendations. After obtaining institutional review board approval, a survey was sent in February 2007 to members of the Society for Pediatric Anesthesia via a web-based survey tool, and re-sent to nonresponders five times over the following 7 months. Overall response rate was 51% (389/768 members). Eighty-five percent of respondents had pediatric anesthesia fellowships, 71% provided anesthesia primarily to children, 71% had been in practice >10 years, 29% had PALS or APLS training during the previous year, and 37% had a patient requiring chest compressions in the previous year. Overall, 89% of respondents knew the correct initial dose of epinephrine (adrenaline) for asystole, 44% knew subsequent management for asystole if initial epinephrine dose was ineffective, 49% knew defibrillation sequence to treat pulseless ventricular tachycardia (VT), and 73% knew the medication sequence to treat pulseless VT. Only those respondents who reported to be in practice for >10 years scored significantly (p<0.0001) better on all resuscitation treatment questions. Respondents who had PALS or APLS training in the previous year or previous 2 years scored significantly better on the defibrillation sequence for pulseless VT (p=0.001 and p=0.045, respectively), and the medication sequence for pulseless VT (p=0.0005 and p=0.011, respectively) when compared with those who had no previous training. Deficiencies exist in the knowledge of current AHA PALS guidelines among anesthesiologists. Formal resuscitation training programs should be considered in ongoing continuing medical education.


Identification and characterization of Mycobacterium tuberculosis antigens in urine of patients with active pulmonary tuberculosis: an innovative and alternative approach of antigen discovery of useful microbial molecules.
Despite the clear need to control tuberculosis, the diagnosis and prevention of this serious disease are poorly developed and have remained fundamentally unchanged for more than 50 years. Here, we introduce an innovative approach to directly identify Mycobacterium tuberculosis antigens produced in vivo in humans with tuberculosis. We combined reversed phase high performance liquid chromatography and mass spectrometry and categorize four distinct M. tuberculosis proteins produced presumably in lung lesions and excreted in the urine of patients with pulmonary tuberculosis. The genes (MT_1721, MT_1694, MT_2462 and MT_3444) coding for these proteins were cloned and the recombinant molecules were produced in Escherichia coli. The proteins were recognized by immunoglobulin G antibodies from tuberculosis patients but not from non-diseased subjects. In addition, the recombinant proteins were recognized strongly by peripheral blood mononuclear cells from healthy purified protein derivative of tuberculin-positive individuals and to a lesser extent from patients with tuberculosis. These molecules are the only proteins reported to date that are derived directly from bodily fluids of tuberculosis patients, therefore are interesting candidate antigens for the development of vaccine and/or antigen detection assay for accurate diagnosis of active tuberculosis.


Expression of the two reovirus S1 gene products in transfected mammalian cells.
Reovirus genomic segment S1, which has been implicated in the viral inhibition of cellular DNA synthesis, is transcribed into a single mRNA that encodes two proteins, the approximately 49-kDa hemagglutinin, sigma 1, and the apparently nonstructural protein, p14. These two polypeptides have been expressed in mammalian cells, together or independently, in order to assess their role in the shutdown of host DNA replication. Results obtained with transient and stable expression systems demonstrate that production of serotype 3 sigma 1 and p14 together or individually is not sufficient to change the kinetics of DNA replication in uninfected cells. However, inhibition of DNA synthesis by reovirus type 1 infection was enhanced in cells producing type 3 sigma 1 and p14 but not sigma 1 by itself. In addition, expression of p14 alone led to increased cytopathic effects following infection by either type 1 or type 3 virus. The results suggest that interactions with other viral components are required to elicit the effects of the S1-specified polypeptides on cellular DNA synthesis.


High quality diet attenuated the positive association between polychlorinated biphenyls and premature mortality among middle-aged and older adults.
Polychlorinated biphenyls (PCBs) have been reported to be a risk factor for premature death, while a high diet quality is thought to lower mortality risk. We aimed to examine whether PCBs were associated with higher all-cause and cause-specific mortality risk and whether such associations could be modified by the diet quality among US middle-aged and older adults. Included were 1259 participants aged 40 years or older from the 1999-2004 National Health and Nutrition Examination surveys. Exposure to PCBs was assessed in non-fasting serum samples, and mortality status was ascertained through December 31, 2019 using the public-use, linked mortality files. Diet quality was assessed using the Healthy Eating Index-2015 based on 24-h dietary recalls. Cox proportional hazard regression was applied to assess the associations of different PCB congener groups with mortality and the modifying effect by the diet quality. During a median follow-up of 17.75 years, 419 deaths occurred, including 131 from cardiovascular disease (CVD) and 102 from cancer. Serum concentrations of dioxin-like PCBs and non-dioxin-like PCBs were significantly associated with all-cause mortality, with hazard ratios (HRs) of 1.84 (95% confidence interval [CI], 1.10, 2.99) and 1.82 (1.09, 3.03) for extreme-tertile comparisons. A significant interaction was noted between dioxin-like PCBs and diet quality (P for interaction: 0.012), with a substantially more pronounced association among participants with a low diet quality (HR, 3.47; 95% CI: 1.29, 9.32), compared to those with a high diet quality (HR, 0.98; 95% CI: 0.40, 2.43). A similar weaker association was observed for total PCBs in participants with a high diet quality (P for interaction: 0.032). However, effect modifications by diet quality were not noted for the associations between different PCB groups and CVD mortality. While our findings need to be validated in other populations and mechanistic studies, they may suggest that a high quality diet could potentially attenuate the harmful effects of chronic PCB exposure.


Use of antiviral drugs for seasonal influenza: Foundation document for practitioners-Update 2019.
This document updates the previous AMMI Canada Foundation Guidance (2013) on the use of antiviral therapy for influenza.


Evaluation and comparison of a CdTe based photon counting detector with an energy integrating detector for X-ray phase sensitive imaging of breast cancer.
To compare imaging performance of a cadmium telluride (CdTe) based photon counting detector (PCD) with a CMOS based energy integrating detector (EID) for potential phase sensitive imaging of breast cancer. A high energy inline phase sensitive imaging prototype consisting of a microfocus X-ray source with geometric magnification of 2 was employed. The pixel pitch of the PCD was 55μm, while 50μm for EID. The spatial resolution was quantitatively and qualitatively assessed through modulation transfer function (MTF) and bar pattern images. The edge enhancement visibility was assessed by measuring edge enhancement index (EEI) using the acrylic edge acquired images. A contrast detail (CD) phantom was utilized to compare detectability of simulated tumors, while an American College of Radiology (ACR) accredited phantom for mammography was used to compare detection of simulated calcification clusters. A custom-built phantom was employed to compare detection of fibrous structures. The PCD images were acquired at equal, and 30% less mean glandular dose (MGD) levels as of EID images. Observer studies along with contrast to noise ratio (CNR) and signal to noise ratio (SNR) analyses were performed for comparison of two detection systems. MTF curves and bar pattern images revealed an improvement of about 40% in the cutoff resolution with the PCD. The excellent spatial resolution offered by PCD system complemented superior detection of the diffraction fringes at boundaries of the acrylic edge and resulted in an EEI value of 3.64 as compared to 1.44 produced with EID image. At equal MGD levels (standard dose), observer studies along with CNR and SNR analyses revealed a substantial improvement of PCD acquired images in detection of simulated tumors, calcification clusters, and fibrous structures. At 30% less MGD, PCD images preserved image quality to yield equivalent (slightly better) detection as compared to the standard dose EID images. CdTe-based PCDs are technically feasible to image breast abnormalities (low/high contrast structures) at low radiation dose levels using the high energy inline phase sensitive imaging technique.


Trichloroethylene induced cutaneous irritation in BALB/c hairless mice: histopathological changes and oxidative damage.
Trichloroethylene (TCE), a colorless and volatile organic solvent, has long been a major chemical hazard during occupational exposure because of its extensive use in industry. Exposure to TCE can cause significant skin lesions, but the effect of TCE on skin irritation has received little attention. We therefore investigated the effect of TCE on skin irritation and oxidative stress using hairless mice. BALB/c hairless mice were subjected to acute and cumulative topical TCE treatment. Skin reactions were evaluated by visual inspection, histopathology examined by microscopy and oxidative stress assessed by measurement of malondialdehyde (MDA) levels, superoxide dismutase (SOD) activities and nitric oxide (NO) production. Under acute and cumulative TCE irritation, the skin developed erythema and edema, and the predominant histopathological features were hyperkeratosis, spongiosis and inflammatory cell infiltrates. In parallel to these morphological changes, acute TCE irritation also concentration-dependently increased MDA levels and inhibited SOD activities of the skin. However, in cumulative irritation, the MDA levels and SOD activities were initially elevated with increased TCE concentrations, but thereafter reduced with further concentration increments; the linear dose-response relationship was not preserved. TCE also concentration-dependently increased NO production both in acute and cumulative irritation. These results suggest that TCE is capable of producing skin irritation effect in vivo, with histopathological changes characterized by hyperkeratosis, spongiosis and inflammatory cell infiltrates. Moreover, oxidative stress may be associated with the clinical manifestations and histopathological abnormalities in TCE-induced skin irritation.


Desoxycorticosterone in normal pregnancy. I. Sequential studies of the secretory patterns of desoxycorticosterone, aldosterone, and cortisol.
Plasma concentrations of desoxycorticosterone (DOC) and aldosterone are markedly elevated in pregnancy. Although DOC secretion in nongravid women has been assumed to be dependent mainly on adrenocorticotropic hormone (ACTH), in a previous study of women in the third trimester of pregnancy it was found to be unresponsive to ACTH, dexamethasone, and variations in salt intake. In this study plasma DOC, aldosterone, and cortisol levels, as well as their responses to ACTH stimulation and overnight dexamethasone suppression, were observed sequentially in seven normal women during the course of pregnancy and at three months post partum. Plasma DOC, aldosterone, and cortisol levels rose substantially during gestation, but increments in DOC did not necessarily coincide with those of the other two. Responses of all three corticosteroids to ACTH were enhanced during the first two trimesters compared to the nongravid state; DOC became unresponsive in the third trimester, while aldosterone and cortisol rose to an even greater extent. Elevated maternal DOC was not decreased significantly by dexamethasone at any stage of pregnancy, while plasma cortisol was suppressed. Nonsuppressibility of DOC with dexamethasone and also the lack of correlation of the rise in DOC with the increase in cortisol during the course of pregnancy suggest that increased DOC secretion in pregnancy does not arise from ACTH-dependent pathways of the maternal adrenal. The loss of responsiveness of DOC to ACTH in the third trimester suggests that the maternal adrenals have undergone an alteration in their steroidogenic response to ACTH, but also may indicate that their output of DOC has reached a maximal rate.


GoPro HERO 4 Black recording of scleral buckle placement during retinal detachment repair.
GoPro and Google Glass technology have previously been used to record procedures in ophthalmology and other medical fields. In this manuscript, GoPro's latest HERO 4 Black edition camera (GoPro Inc, San Mateo, Calif.) will be used to record the placement of a scleral buckle during retinal detachment surgery. GoPro HERO 4 Black edition camera, which records 4K-quality video with a resolution of 3840 (pixels) x 2160 (lines), was mounted on a head strap to record placement of a scleral buckle for a retinal detachment. Excellent video quality was achieved with the 4K SuperView setting. Bluetooth connection with an Apple iPad (Apple Inc, Cupertino, Calif.) provided live streaming and use of the GoPro App. Zoom, horizontal/vertical alignment, exposure, and contrast adjustments were made with postproduction editing on GoPro Studio software. Video recording with the GoPro HERO 4 Black edition camera is an excellent way to document extraocular procedures to improve medical education, self-training, or medicolegal documentation.


Treatment of partially accommodative esotropia in children using a medial rectus muscle fenestration technique.
To report the results of bilateral fenestration of the medial rectus muscle in cases of partially accommodative esotropia in pediatric patients. In this fenestration technique, two splitting incisions are made by blunt dissection parallel to the muscle fibers on the superior and inferior borders of the medial rectus muscle, leaving a thin strip of muscle fibers on each edge. The wide, central part of the muscle is excised from its insertion to a point 5-8 mm from the insertion, depending on the angle of the esotropia. Sutures are not used in this procedure. Children with partially accommodative esotropia and no high ratio of accommodative convergence to accommodation who underwent surgery from February 2018 to August 2019 were prospectively enrolled. The success rate was defined as alignment within 8 prism diopters of orthotropia at the last follow up. A total of 61 children were included. The procedure was well tolerated by patients and reduced the angle of esotropia for distance from 22.20Δ ± 4.22Δ to 2.72Δ ± 4.71Δ (P < 0.001) and caused no incomitance or distance-near disparity. Satisfactory horizontal alignment defined as alignment within 8Δ of orthotropia at distance was achieved in 88% of the cases at 3-6 months' follow-up. There were no overcorrections. In our study cohort, the fenestration technique reduced the angle of deviation in cases of partially accommodative esotropia.


Interacting role of thyroxine and growth hormone in the hepatic synthesis of alpha 2u-globulin and its messenger RNA.
Hypophysectomy completely abolishes and thyroidectomy results in a 90% reduction in the hepatic content of alpha 2u-globulin and its mRNA in the male rat. Thyroid hormone is also known to be required for the synthesis and secretion of pituitary growth hormone. In the hypothyroid rat either thyroxine or growth hormone was found to increase the activity and number of sequences of the mRNA for alpha 2u-globulin (measured by translational assay and hybridizational analysis with a cloned cDNA probe) to the euthyroid level. Treatment of hypophysectomized rats with a hormone combination containing growth hormone but not thyroxine increased the hepatic level of the mRNA for alpha 2u-globulin to that of normal animals. From these results we conclude that thyroxine indirectly influences the hepatic concentration of the mRNA for alpha 2u-globulin through its effect on pituitary growth hormone. Although administration of growth hormone to hypothyroid animals raised the hepatic concentration of alpha 2u-globulin mRNA to the euthyroid level, synthesis of alpha 2u-globulin remained low (50% of the normal). Complete recovery of alpha 2u-globulin synthesis required thyroxine. Therefore, in addition to an indirect effect on the hepatic level of alpha 2u-globulin mRNA, thyroxine also directly influences the synthesis of this protein. This direct effect of thyroxine on alpha 2u-globulin synthesis seems to be exerted at a step distal to the formation of mature mRNA.


Mechanical ventilation of patients with acute lung injury.
Ventilatory management of patients with acute lung injury (ALI), particularly its most severe subset, acute respiratory distress syndrome (ARDS), is complex. Newer lung protective strategies emphasize measures to enhance alveolar recruitment and avoid alveolar overdistention, thus minimizing the risk of ventilator-induced lung injury (VILI). Key components of such strategies include the use of smaller-than-conventional tidal volumes which maintain peak transpulmonary pressure below the pressure associated with overdistention, and titration of positive end-expiratory pressure to promote maximal alveolar recruitment. Novel techniques, including prone positioning, inverse ratio ventilation, tracheal gas insufflation, and high frequency ventilation, are considerations in severe ARDS. No single approach is best for all patients; adjustment of ventilatory parameters to individual characteristics, such as lung mechanics and gas exchange, is required.


Laparoscopic extirpation of a giant ovarian cyst.
The differential diagnosis of unilocular intraabdominal cysts includes ovarian, gastrointestinal, urological, and lymphatic processes. They occur at all ages and can be benign or malignant. We present a case of a 17-year-old female with asymptomatic abdominal distension. Ultrasonography (US) revealed a 20 x 21-cm unilocular cystic mass with smooth surface lining. Paracentesis was performed during diagnostic laparoscopy, recovering more than 7 L of clear fluid. The cyst and left adnex were completely removed laparoscopically and diagnosis of ovarian cystadenoma was made. The patient made a quick and uneventful recovery. In all cases of abdominal distension, US must be performed and a tumor marker profile consisting of AFP, LDH, testosterone, estradiol, and CA-125 must be established in order to differentiate between benign and malignant processes. When the latter is suspected, additional computerized tomographic scanning must be performed. In this case, a normal tumor marker profile and benign ultrasonographic appearance excluded the possibility of malignancy. Conventional treatment in these large cysts is laparotomy. We propose that complete laparoscopic drainage and extirpation should be the treatment of choice, regardless of cystic size.


A new graft material for myringoplasty: bacterial cellulose.
We aimed to determine the success rate of bacterial cellulose (BC) myringoplasty in tympanic membrane (TM) perforation. We reviewed the clinical records of 12 patients (16 ears) who underwent BC myringoplasty for long-standing TM perforations (>6 months) between March 2012 and January 2015. The mean duration of postoperative follow-up was 12.8 (range 6-24) months. In all patients, the perforation involved less than 50 % of the tympanic membrane, and the air-bone gap was ≤30 dB on the operative side. The age, gender, preoperative air average, bone average, air-bone gap, perforation size and location, and postoperative TM microscopic examinations of the patients were recorded. Following the BC myringoplasty, complete coverage of the perforation occurred in the first 6 months in 13 of 16 ears (81.3 %), although retraction occurred in two of these ears within 6 months. In three ears (18.8 %), the perforation persisted during the first postoperative month. The pre- and postoperative average air threshold was 19.56 (range 7-75) and 15.69 (range 5-75) dB, respectively. The pre- and postoperative average air-bone gap was 9.25 (range 0-25) and 5.63 (0-25) dB, respectively. Both the air threshold and air-bone gap improved postoperatively (both p = 0.008). No complications such as infection and granulation tissue formation were detected in any patient. BC is a safe graft material that is inexpensive, easy-to-use, and provides a high success rate in small tympanic membrane perforations. However, further studies of large tympanic membrane perforations with more samples and long-term follow-up are required.


Neurologic Complications of Solid Organ Transplantation.
Among patients receiving solid organ transplants, approximately one-third will develop neurologic symptoms. Most of these neurologic symptoms will occur within 30 days of their transplantation. These neurologic symptoms include neurotoxicity of immunosuppressive agents, seizures, encephalopathy, cerebrovascular events, opportunistic infections, posttransplant lymphoproliferative disorder, and central pontine myelinosis. Some neurologic complications are seen more frequently in specific organ transplant recipients. For example, ischemic stroke is seen more frequently in heart and kidney transplant patients compared with other solid organ transplant recipients. This article is a review of the main neurologic complications after solid organ transplantation.


Surface reactivity enhancement on a Pd/Bi2Te3 heterostructure through robust topological surface states.
We present a study of the surface reactivity of a Pd/Bi2Te3 thin film heterostructure. The topological surface states from Bi2Te3, being delocalized and robust owing to their topological natures, were found to act as an effective electron bath that significantly enhances the surface reactivity of palladium in the presence of two oxidizing agents, oxygen and tellurium respectively, which is consistent with a theoretical calculation. The surface reactivity of the adsorbed tellurium on this heterostructure is also intensified possibly benefitted from the effective transfer of the bath electrons. A partially inserted iron ferromagnetic layer at the interface of this heterostructure was found to play two competing roles arising from the higher-lying d-band center of the Pd/Fe bilayer and the interaction between the ferromagnetism and the surface spin texture of Bi2Te3 on the surface reactivity and their characteristics also demonstrate that the electron bath effect is long-lasting against accumulated thickness of adsorbates.


Does submucosal diathermy to the inferior turbinates reduce nasal resistance to airflow in the long term?
The operation of submucosal diathermy is commonly performed for the relief of nasal obstruction due to mucosal swelling. In this study the effect of the procedure on nasal resistance to airflow is assessed by rhinomanometry. The results show that although the operation is effective in the short term (two months), there is no significant difference between the nasal resistances prior to surgery and at 15 months after surgery.


Sp transcription factor family and its role in cancer.
Specificity protein 1 (Sp1) and other Sp and Krüppel-like factor (KLF) proteins are members of a family of transcription factors which bind GC/GT-rich promoter elements through three C(2)H(2)-type zinc fingers that are present at their C-terminal domains. Sp1-Sp4 proteins regulate expression of multiple genes in normal tissues and tumours. There is growing evidence that some Sp proteins play a critical role in the growth and metastasis of many tumour types by regulating expression of cell cycle genes and vascular endothelial growth factor. Sp/KLF proteins are also potential targets for cancer chemotherapy.


Content analysis: concepts, methods and applications.
Content analysis is much more than a naive technique that results in a simplistic description of data. It allows the researcher to test theoretical issues to enhance understanding of the data. Using applications from the nursing and health literature, this paper will explain key concepts and methodological issues, including strategies for data analysis.


Arthroscopic debridement for soft tissue ankle impingement.
To assess the response to treatment in patients with soft tissue impingement of the ankle managed with arthroscopic debridement. Forty-one ankle arthroscopies were performed for soft tissue impingement between April 2007 and April 2009. There were 26 men and 15 women and the mean age was 30.1 years. Arthroscopy was performed on an average of 21 months after injury. The Visual-Analogue-Scale Foot and Ankle (VASFA) score and Meislin's criteria were used to assess the response to treatment. The mean pre-operative VASFA score was 44.5. This increased to 78.3 postoperatively (p < 0.0001). According to Meislin's criteria, there were 34 good or excellent results, five fair and two poor results. Pre-operative magnetic resonance imaging was useful in detecting tears of the anterior talofibular ligament and excluding osteochondral defects; however, synovitis and soft tissue impingement was under-reported. Arthroscopy is an effective method for the diagnoses and treatment of soft tissue impingement of the ankle joint. This condition is under-reported on MRI.


Transzygomatic Kirschner wire fixation for the treatment of blowout fracture.
Total orbital floor reconstruction with sheet-shape materials is available for the treatment of extensive and crushed-type blowout fractures. Simple blowout fractures, on the other hand, require only manual reduction without fixation. Although several types of blowout fractures do not require total reconstruction, some fixation is usually necessary. Eighteen cases of blowout fracture were treated with transzygomatic Kirschner wire fixation between 2002 and 2009. This technique was applied to simple fracture cases in which periorbital soft tissue re-herniated through the floor defect into the maxillary sinus after manual reduction, despite improvement of the extra-ocular muscle entrapment. The wire was used to directly support the fracture segment in five cases and used together with a maxillary sinus anterior wall bone graft in 13 cases. Mean follow-up was 12.5 months. Mild diplopia remained as a subjective symptom in one case. None of the cases developed major complications or conspicuous scars on the cheek. Transzygomatic Kirschner wire fixation for blowout fracture has the advantages of precise and rigid fixation of all parts of the inferior floor, minimal morbidity without requiring an orbital approach and long-term safety without artificial remnants. This technique can be applied for the treatment of simple blowout fractures.


Prenatal nicotine exposure and behavior.
Prenatal exposure to nicotine has been associated with changes in behavioral indices in offspring. Flank marking, a scent-marking behavior in golden hamsters, appears to be controlled by arginine vasopressin (AVP) neurons in the hypothalamus. The present study examines the effects of prenatal exposure to nicotine on the vasopressinergic system associated with flank marking behavior.


Access to hospital interpreter services for limited English proficient patients in New Jersey: a statewide evaluation.
We surveyed New Jersey (NJ) hospitals to assess current language services and identify policy recommendations on meeting limited English proficiency (LEP) patients' needs. Survey with 37 questions regarding hospital/patient features, interpreter services, and resources/policies needed to provide quality interpreter services. Sixty-seven hospitals responded (55% response rate). Most NJ hospitals have no interpreter services department, 80% provide no staff training on working with interpreters, 31% lack multilingual signs, and 19% offer no written translation services. Only 3% of hospitals have full-time interpreters, a ratio of 1 interpreter:240,748 LEP NJ residents. Most hospitals stated third-party reimbursement for interpreters would be beneficial, by reducing costs, adding interpreters, meeting population growth, and improving communication. Most NJ hospitals have no full-time interpreters, interpreter services department, or staff training on working with interpreters, and deficiencies exist in hospital signage and translation services. Most NJ hospitals stated third-party reimbursement for interpreter services would be beneficial.


Trametes versicolor ligninase: isozyme sequence homology and substrate specificity.
The substrate specificity of three ligninase isozymes from the white-rot fungus Trametes versicolor has been investigated using stereochemically defined synthetic dimeric models for lignin. The isozymes have been found to attack non-phenolic beta-O-4 as well as beta-1 lignin model compounds. This finding confirms the classification of the isozymes from T. versicolor as ligninases. The amino-terminal residues of the three isozymes from T. versicolor have been determined using Edman degradation. Minor differences found between the sequences suggest the existence of several structural genes for ligninase in T versicolor. Comparisons have been made with the sequences of three previously reported ligninases from Phanerocompaete chrysosporium, another lignin-degrading fungus. One of the sequences from P. chrysosporium is distinctly more similar to the T. versicolor isozymes than to the other two sequences from P. chrysosporium.


Modified red light 5-aminolevulinic acid photodynamic therapy versus low-dose isotretinoin therapy for moderate to severe acne vulgaris: A prospective, randomized, multicenter study.
Modified 5-aminolevulinic acid photodynamic therapy (M-PDT) and isotretinoin (ISO) are effective treatments for moderate to severe acne vulgaris. To evaluate the efficacy and adverse effects of M-PDT and ISO for moderate to severe acne vulgaris. A multicenter, randomized clinical trial was conducted with participants randomly assigned to the M-PDT group (up to 5 weekly sessions following manual comedone extraction) or the ISO group (oral ISO, 0.5 mg/kg/d for 6 months) and followed up to 6-months after therapy. A total of 152 patients were allocated. The overall effective rates in the M-PDT group were significantly higher than the ISO group at 1 month (67.74% vs 10.26%), whereas the opposite was the case 1 month after treatment (75.81% vs 97.44%). Time to achieve 50% lesion improvement in the M-PDT group was significantly less than the ISO group (1 vs 8 weeks). Overall, 70.67% of the ISO group patients experienced systemic side effects such as hepatotoxicity, whereas side effects were skin-limited in the M-PDT group. Limitations of this study included relatively low numbers of participants and high withdrawal rate. M-PDT offers a more rapid onset of improvement, comparable overall efficacy, good tolerability, and comparable durability of response compared with ISO.


Characterization of tyramine beta-hydroxylase in planarian Dugesia japonica: cloning and expression.
The planarian Dugesia japonica has a relatively well-organized central nervous system (CNS) consisting of a brain and ventral nerve cords (VNCs), and can completely regenerate it CNS utilizing pluripotent stem cells present in the mesenchymal space. This remarkable capacity has begun to be exploited for research on neural regeneration. Recently, several kinds of molecular markers for labeling of neural subtypes have been reported in planarians. These molecular markers are useful for visualizing the distinct neural populations in planarians. In this study, we isolated a cDNA encoding tyramine beta-hydroxylase (TBH), an octopamine (OA) biosynthetic enzyme, by degenerate PCR in the planarian D. japonica, and named it DjTBH (D. japonica tyramine beta-hydroxylase). In order to examine whether DjTBH contributes to OA biosynthesis, we measured the OA content in DjTBH-knockdown planarians created by RNA interference. In addition, to examine the specificity of DjTBH for OA biosynthesis, we measured not only OA content but also noradrenaline (NA) content, because NA is synthesized by a pathway similar to that for OA. According to high-performance liquid chromatography analysis, the amount of OA, but not NA, was significantly decreased in DjTBH-knockdown planarians. In addition, we produced anti-DjTBH antibody to visualize the octopaminergic neural network. As shown by immunofluorescence analysis using anti-DjTBH antibody, DjTBH-immunopositive neurons were mainly distributed in the head region, and elongated their dendrites and/or axons along the VNCs. In order to visualize octopaminergic and dopaminergic nervous systems (phenolamine/catecholamine nervous system) in the planarian CNS, double-immunofluorescence analysis was carried out using both anti-DjTBH antibody and anti-DjTH (a planarian tyrosine hydroxylase) antibody. DjTBH-immunopositive neurons and DjTH-immunopositive neurons mainly formed distinct neural networks in the head region. Here, we demonstrated that DjTBH clearly contributes to OA biosynthesis, and DjTBH antibody is a useful tool for detecting octopaminergic neurons in planarians.


Tracking of radiation exposure in pediatric stone patients: The time is now.
Despite the increasing incidence of pediatric nephrolithiasis, there is little data quantifying the radiation exposure associated with treatment of this disease. In this study, pediatric patients with nephrolithiasis who were managed at a single institution were identified, and the average fluoroscopy time and estimated radiation exposure associated with their procedures were reported. Stone procedures performed on pediatric patients between 2005 and 2012 were retrospectively identified. Procedures were classified as primary ureteroscopy (URS), stent placement prior to ureteroscopy (SURS), percutaneous nephrolithotomy (PCNL), and bilateral ureteroscopy (BLURS). Patient demographic information, stone size, stone location, number of radiographic images, and fluoroscopy times were analyzed. A total of 152 stone procedures were included in the final analysis (92 URS, 38 SURS, eight BLURS and 14 PCNL). Mean patient age at time of stone treatment was 15.94 ± 4.1 years. Median fluoroscopy times were 1.6 (IQR 0.8-2.4), 2.1 (IQR 1.6-3.0), 2.5 (IQR 2.0-2.9), and 11.7 (IQR 5.0-18.5) minutes for URS, SURS, BLURS and PCNL, respectively. There was a moderate correlation between stone size and fluoroscopy time (r = 0.33). When compared with ureteroscopic procedures, PCNL was associated with a significantly higher fluoroscopy time (11.7 vs 2.1 min, P < 0.001). The estimated median effective dose was 3 mSv for ureteroscopic procedures and 16.8 mSv for PCNL. In addition to radiation exposure during treatment, patients in this cohort were exposed to an average of one (IQR1-3) CT scan and three (IQR 1-8) abdominal X-rays. No new malignancies were identified during the limited follow-up period. Radiation exposure during treatment of pediatric stone disease is not trivial, and is significantly greater when PCNL is performed. Given the recommended maximum effective dose of 50 mSv in any one year, urologists should closely monitor the amount of fluoroscopy used, and consider the potential for radiation exposure when choosing the operative approach. Prospective studies are currently underway to elucidate precise dose measurements and localize sites of radiation exposure in children during stone treatment.


Kinetic analysis of the active site of an intracellular beta-glucosidase fromCellulomonas biazotea.
Purified beta-glucosidase fromCellulomonas biazotea had an apparentK (m) andV for 2-nitrophenyl beta-D: -glucopyranoside (oNPG) of 0.416 mmol/L and 0.22 U/mg protein, respectively. The activation energy for the hydrolysis of pNPG of beta-glucosidase was 65 kJ/mol. The inhibition by Mn(2+) vs. oNPG of parental beta-glucosidase was of mixed type with apparent inhibition constants of 0.19 and 0.60 micromol/L for the enzyme and enzyme-substrate complex, respectively. Ethanol at lower concentrations activated while at higher concentrations it inhibited the enzyme. The determination of apparent pK (a)'s at different temperatures and in the presence of 30 % dioxane indicated two carboxyl groups which control theV value. The thermal stability of beta-glucosidase decreased in the presence of 10 % ethanol. The half-life of beta-glucosidase in 1.75 mol/L urea at 35 degrees C was 145 min, as determined by 0-9 mol/L transverse urea gradient-PAGE.


QoL Following Dacryocystorhinostomy: Linguistic Adaptation of Italian Version of GBI.
The Glasgow Benefit Inventory (GBI) is a generic patient recorded outcome measure assessing the quality of life of patients undergoing ear nose and troth surgery. Although largely used in the clinical practice, it has never been adapted and validated in the Italian language. The aim of the study was to translate the original GBI from English to Italian and to examine its reliability for use in the Italian adult population of patients undergoing endonasal endoscopic dacryocystorhinostomy. After translation and back-translation of the original English we evaluated the reliability of GBI for use in 79 Italian adults undergoing dacryocystorhinostomies. Reliability of GBI-IT was examined by the internal consistency of the scale (using the Cronbach's alpha coefficient), and by the test-retest analysis. The GBI-IT showed adequate internal consistency (Cronbach's alpha = 0.85 for the total scale). The total GBI-IT score showed a strong correlation in retests (CCC 0.87). In conclusion, our study showed that the GBI-IT has satisfactory internal consistency and reliability and is equivalent to the original English version. In addition, it can be considered a valuable measure for both clinical and research uses.


Second canal in mesiobuccal root of maxillary molars is correlated with root third and patient age: a cone-beam computed tomographic study.
There is little evidence supporting the use of cone-beam computed tomographic (CBCT) scanning in root canal anatomy investigation. This study aimed to investigate the presence of second mesiobuccal canals (MB2) in different thirds of the mesiobuccal root of first and second maxillary molars using CBCT scanning and to correlate findings with patient sex and age. A total of 100 male and female adult patients with healthy, untreated, well-developed maxillary molars were enrolled. A total of 343 teeth were analyzed in vivo using CBCT scanning: 79 right and 79 left maxillary first molars (1MR and 1ML) and 94 right and 91 left maxillary second molars (2MR and 2ML). Teeth with 3 roots were identified, and the presence of MB2 canals in different thirds was correlated with patient sex and age. Maxillary molars with 3 roots showed a high percentage of MB2 canals: 1MR, 86.1%; 1ML, 91.0%; 2MR, 87.5%; and 2ML, 79.3%. MB2 canals were less prevalent in the middle and apical thirds than in the coronal third. There were no significant associations between the overall presence of MB2 canals and patient sex. Older age (ie, 51-70 years) was associated with fewer canals in 1ML and 2ML. All age groups showed fewer MB2 canals in the apical versus the coronal third. The prevalence of MB2 canals decreases as the root canal approaches the apical third and as age increases. No association with sex was observed. CBCT scanning proved effective in mapping MB2 canals present in different thirds of the root.


Determinants of Astrocytic Pathology in Stem Cell Models of Primary Tauopathies.
Astrocytic tau aggregates are seen in several primary and secondary tauopathies, including progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and chronic traumatic encephalopathy (CTE). In all cases, astrocytic tau consists exclusively of the longer (4R) tau isoform, even when adjacent neuronal aggregates consist of a mixture of 3- and 4R tau, as in CTE. The reasons for this and the mechanisms by which astrocytic tau aggregates form remain unclear. We used a combination of RNA in situ hybridization and immunofluorescence in post-mortem human brain tissue, as well as tau uptake studies in human stem cell-derived astrocytes, to determine the origins of astrocytic tau in 4R tauopathies. We found that astrocytes across tauopathies do not upregulate tau mRNA expression between diseases or between tau-positive and -negative astrocytes within PSP. We then found that stem cell-derived astrocytes preferentially take up long isoform (4R) labeled recombinant tau and that this uptake is impaired by induction of reactivity with inflammatory stimuli or nutritional stress. Astrocytes exposed to either 3R or 4R tau also showed downregulation of genes related to astrocyte differentiation. Our findings suggest that astrocytes preferentially take up neuronal 4R tau from the extracellular space, which potentially explains why astrocytic tau aggregates contain only 4R tau, and that tau uptake is impaired by decreased nutrient availability or neuroinflammation, both of which are common in the aging brain.


The obesity of middle age: a common variety of Cushing's syndrome due to a chronic increase in adrenocorticotrophin (ACTH) and beta-endorphin activity.
The common obesity of middle age presents a set of features that strongly resembles the cardinal symptoms of Cushing's syndrome: obesity of the face (moon face), upper back (buffalo hump) and trunk (pot belly) accompanied by signs of protein-wasting. In non-obese individuals who remain at a constant weight throughout life, the proportion of adipose tissue increases with age at the expense of lean tissue loss. Thus, a mild version of Cushing's syndrome may be part of the normal aging process. A more intense version of this process may occur in overweight adults. Excess and chronic activity of two pituitary hormones may contribute to this adiposity. Both hormones are produced in the same pituitary cell by cleavage from a common large precursor known as pro-opiocortin. One hormone is adrenocorticotrophin (ACTH), which stimulates the release of the glucocorticoid hormones. These hormones promote the conversion of bodily proteins to glucose (gluconeogenesis). The other pituitary hormone is beta-endorphin, a stimulant of appetite that causes the release of insulin. This pancreatic hormone promotes the conversion of glucose and fatty acids to triglycerides (lipogenesis). Three different etiologies are suggested for the excessive and chronic action of these two pituitary hormones: tumors that increase the number of cells that synthesize pro-opiocortin; mutant strains that produce excessive amounts of ACTH and beta-endorphin such as the genetically obese mouse (ob/ob) and rat (fa/fa); and an age-determined shift in the type of cleavage enzymes present in the pro-opiocortin cell that favors ACTH and beta-endorphin production.


Delayed carotid shunt occlusion detected by electroencephalographic monitoring.
Little has been recorded in the anesthesia literature concerning the changes in the electroencephalogram (EEG) that may occur during carotid endarterectomy many minutes after shunt placement and restoration of flow and that may be attributed to "delayed" shunt occlusion or cerebral emboli. We describe a patient in whom EEG changes indicative of cerebral ischemia occurred at the time of carotid clamping. The changes resolved promptly after placement of a carotid shunt but recurred 11 minutes later. Because of the EEG changes, the carotid shunt was evaluated and found to have become occluded. EEG monitoring was crucial to the detection of shunt occlusion in the absence of other systemic changes or surgical difficulties. The rapidity and magnitude of the changes in the EEG suggest that, if the occlusion had not been discovered and the patency of the shunt restored, the patient would have been at increased risk for neurologic injury.


Absence of AGPAT2 impairs brown adipogenesis, increases IFN stimulated gene expression and alters mitochondrial morphology.
Biallelic loss of function variants in AGPAT2, encoding 1-acylglycerol-3-phosphate O-acyltransferase 2, cause congenital generalized lipodystrophy type 1, a disease characterized by near total loss of white adipose tissue and metabolic complications. Agpat2 deficient (Agpat2-/-) mice completely lacks both white and interscapular brown adipose tissue (iBAT). The objective of the present study was to characterize the effects of AGPAT2 deficiency in brown adipocyte differentiation. Preadipocytes obtained from newborn (P0.5) Agpat2-/- and wild type mice iBAT were differentiated into brown adipocytes, compared by RNA microarray, RT-qPCR, High-Content Screening (HCS), western blotting and electron microscopy. 1) Differentiated Agpat2-/- brown adipocytes have fewer lipid-laden cells and lower abundance of Pparγ, Pparα, C/ebpα and Pgc1α, both at the mRNA and protein levels, compared those to wild type cells. Prmd16 levels were equivalent in both, Agpat2-/- and wild type, while Ucp1 was only induced in wild type cells, 2) These differences were not due to lower abundance of preadipocytes, 3) Differentiated Agpat2-/- brown adipocytes are enriched in the mRNA abundance of genes participating in interferon (IFN) type I response, whereas genes involved in mitochondrial homeostasis were decreased, 4) Mitochondria in differentiated Agpat2-/- brown adipocytes had altered morphology and lower mass and contacting sites with lipid droplets concomitant with lower levels of Mitofusin 2 and Perlipin 5. AGPAT2 is necessary for normal brown adipose differentiation. Its absence results in a lower proportion of lipid-laden cells, increased expression of interferon-stimulated genes (ISGs) and alterations in mitochondrial morphology, mass and fewer mitochondria to lipid droplets contacting sites in differentiated brown adipocytes.


Analysis of the Effectiveness of 3D Printed Patient-Specific Implants for Reconstruction of Maxillary Defect Secondary to Mucormycosis.
Patients affected with mucormycosis of maxilla have been increasing following Covid-19 infections. We followed the reconstruction of the maxilla using 3D manufactured patient-specific implants. The additive manufacturing technology is capable of fabricating custom-made titanium implants precisely for oral and maxillofacial reconstructions. To analyse the effectiveness of 3D manufactured patient-specific implants in the reconstruction of maxilla affected by mucormycosis secondary to Covid-19. Methodology: This study was conducted among 20 patients receiving patient-specific implants for surgical and prosthetic reconstruction of the maxilla. The parameters analysed at baseline, 3 months, 6 months, and 12 months were pain, implant exposure, infection, wound dehiscence, fit of implant, postoperative surgical rating scale, and patient experience evaluation rating scale. Inferential Statistics revealed a positive correlation. From the present data, it can be concluded that within the limitations of the study, patient-specific implant systems are an effective treatment strategy for the reconstruction of the maxilla affected by mucormycosis secondary to Covid-19. More studies with larger sample size and longer follow-up periods are required to substantiate the results from the present study. The online version contains supplementary material available at 10.1007/s12663-023-01922-7.


Up-regulated expression of ADAM17 in human colon carcinoma: co-expression with EGFR in neoplastic and endothelial cells.
The ADAM17 metalloproteinase (a disintegrin and metalloprotease 17) controls epidermal growth factor receptor (EGFR) activation through regulated shedding of EGFR ligands. With the advent of new therapeutic options targeting EGFR signalling in colon carcinoma, it was decided to determine ADAM17 status in relation to clinico-pathological parameters and EGFR status. To this end, a series of 39 colon carcinomas were analysed. Immunohistochemistry and immunofluorescence were used to localize ADAM17, EGFR, and the activated forms of EGFR. The activated form of ADAM17 was assessed in primary cancers and colon cell lines by immunoblotting. ADAM17 and EGFR mRNA levels were assessed by quantitative RT-PCR. Chromogenic in situ hybridization (CISH) was used to quantify the HER1 gene. ADAM17 was strongly expressed in all tumours, by both neoplastic and endothelial cells. It was expressed both as a pro- and as an active form in tumours and colonic cancer cell lines. ADAM17 mRNA was up-regulated in 90% of colon carcinomas relative to the paired normal mucosa, whatever the tumour grade or stage. When present, activated EGFR was co-expressed with ADAM17 by colon carcinomas, although at a variable level among tumour cells, and by endothelial cells. EGFR mRNA was overexpressed in 77% of colon carcinomas compared with the paired normal mucosa. One case showed high-level amplification of HER1. In conclusion, this study is the first demonstration that ADAM17 is overexpressed in human primary colon carcinoma, whatever the tumour stage and differentiation and whatever the level of EGFR expression. Its co-expression with EGFR, in both neoplastic and endothelial cells, suggests a role for ADAM17 in tumour growth and angiogenesis.


Analysis of fiducial markers used for on-line verification in the external-beam radiotherapy of patients with cranial tumours.
Evaluate the fiducial marker-based position verification in the external-beam radiotherapy of patients with cranial tumour. Thirteen patients with intracranial tumours were treated with external- beam radiotherapy using 3 gold markers implanted in the skull. Before each fraction the patient was positioned on the treatment table and 2 orthogonal portal images were performed to localise the 3 gold seeds and the target position was calculated using a commercialised computer program (ISOLOC software, MEDTEC). This program provides the couch movements required to move the target to the isocentre. When the set-up error was corrected using the coordinates of the 3 markers, the final movements were less than 2 mm in all cases: lateral, mean v., 1.21 mm; longitudinal, 1.23 mm; and anteroposterior, 1.18 mm. No serious complications related to the gold marker insertion were noted. The use of 3 implanted fiducial seeds is an optimal technique for precise set-up in patients with brain tumours treated with external radiotherapy. This commercial system is highly suitable for fractionated stereotactic irradiation.


New thermodynamic characterization and transition mechanism of DNA duplex formation.
A new transition mechanism of DNA duplex association was proposed and a segregated transition model (STM) was further derived. The experimental results in various molar ratios showed that the duplex association transition is imperfect and the thermodynamic properties and self-transition behavior of single strands exert a significant influence on DNA duplex formation.


Linkage of monogenic infantile hypertrophic pyloric stenosis to chromosome 16q24.
Infantile hypertrophic pyloric stenosis (IHPS) is the most common inherited form of gastrointestinal obstruction in infancy. The disease is considered a paradigm for the sex-modified model of multifactorial inheritance and affects males four times more frequently than females. However, extended pedigrees consistent with autosomal dominant inheritance have been documented. We have analysed data from an extended IHPS family including eight affected individuals (five males and three females) and mapped the disease locus to chromosome 16q24 (LOD score=3.7) through an SNP-based genome wide scan. Fourteen additional multiplex pedigrees did not show evidence of linkage to this region, indicating locus heterogeneity.


Effectiveness of implanting catheterizable channels into intestinal segments.
To assess the effectiveness of implanting continent catheterizable channels (CCCs) into bowel segments used for bladder augmentation or substitution. The records of patients operated on between 2000 and 2003 were reviewed. CCCs were created using the appendix or a transverse tubularized bowel, and were implanted either in the intestinal segment of an augmentation or into an intestinal continent reservoir. Implantation into the intestinal segment was preferred over the native bladder, when it allowed the stoma to be placed at the umbilicus, creating the shortest possible channel. Ease of catheterization and continence through the stoma were evaluated by clinic interviews or record review. Thirty-two patients (16 males) were 11.6 years old (mean) at the time of operation. Mean follow-up was 26 months. The CCCs were implanted in colon (24), ileum (six) and into a seromuscular colocystoplasty (two). At the last follow up all patients had satisfactory continence through the catheterizable stoma, but the continence rate after the initial procedure was 87.5% (28/32). Three patients required revision because of a short tunnel and became continent. One patient experiences occasional incontinent episodes when the bladder is full, but has not been re-operated on. Three patients experienced difficulties with catheterization attributed to a skin-level stenosis and have been revised. The overall revision rate was 18%. CCCs constructed with either appendix or transverse tubularized bowel implanted into intestinal segments had a success rate comparable to that reported by others when implanted in the native bladder. The umbilical location of the stoma had significant cosmetic advantages and no apparent disadvantages.


[Sperm DNA fragmentation index and the success rate of IVF/ICSI].
Sperm DNA fragmentation index (DFI) refers to the percentage of DNA strand breaks in the total sperm. Many studies suggest that elevated DFI can lead to male infertility and early spontaneous abortion. High-DFI patients are more likely to fail in assisted reproduction and preliminary treatment or prevention methods have been developed for this population. This review focuses on the impact of DFI on clinical pregnancy outcomes and progress in the studies of its treatment.


Reversal of developmental delays in iron-deficient anaemic infants treated with iron.
Iron-deficient anaemic infants perform worse in tests of mental and motor development than do iron-sufficient infants of a comparable age. A randomised, double-blind trial was done to monitor the effects of iron supplementation on performance in the Bayley scales of mental and motor development among 12-18-month-old infants in Indonesia. Iron-deficient anaemic infants (n = 50) were assigned randomly to receive dietary ferrous sulphate or placebo for 4 month. Similar treatment randomisation was done among nonanaemic iron-deficient (n = 29) and iron-sufficient (n = 47) infants. Before intervention, the mean mental and motor scores of the iron-deficient anaemic infants were significantly (p < 0.01) lower than those of the nonanaemic iron-deficient and iron-sufficient classes. After intervention, developmental delays were reversed among iron-deficient anaemic infants who had received iron but they remained the same among placebo-treated iron-deficient anaemic infants. Neither ferrous sulphate nor placebo had significant effects on the scores of the other two iron-status classes. The poor performance of 12-18-month-old iron-deficient anaemic infants in the Bayley scales of mental and motor development can be improved to the level of performance of iron-sufficient infants by treatment with ferrous sulphate.


[Periprosthetic fractures: basics, classification and treatment principles].
Periprosthetic fractures (PPFx) are becoming an increasingly important topic in orthopedics and trauma surgery due to the rising number of endoprosthetic joint replacements. The recently published unified classification system (UCS) has replaced numerous historical classification systems and can be applied to all PPFx regardless of the bone or joint involved. The treatment of PPFx requires individual therapeutic concepts taking patient-dependent and patient-independent factors into consideration. The conservative treatment of PPFx is only justified in exceptional situations. In contrast, the choice between operative treatment and deciding between osteosynthesis or revision arthroplasty is particularly based on the assessment of the implant stability. In order to achieve fracture consolidation and also a good functional outcome, knowledge of the basic biomechanical principles of operative (osteosynthesis or endoprosthesis) treatment of periprosthetic fractures is necessary.


Newborn screening: A complex system that requires a culture of safety.
As health care providers and organizations, we have a responsibility to examine our practices and systems for opportunities to improve quality and health outcomes. Today a critical opportunity exists in the newborn screening (NBS) system, which touches every one of the approximately 4 million babies born annually in the United States. This opportunity involves improving the quality of NBS by developing a culture of safety to prevent errors that in NBS represent missed babies and preventable morbidity and mortality. This commentary will explore the "culture of safety" for NBS, including the high reliability organization (HRO) paradigm and normal accident theory (NAT), which have been effective in reducing systems failures in other complex environments.


Antibody arrays in biomarker discovery.
All of life is regulated by complex and organized chemical reactions that help dictate when to grow, to move, to reproduce, and to die. When these processes go awry, or are interrupted by pathological agents, diseases such as cancer, autoimmunity, or infections can result. Cytokines, chemokines, growth factors, adipokines, and other chemical moieties make up a vast subset of these chemical reactions that are altered in disease states, and monitoring changes in these molecules could provide for the identification of disease biomarkers. From the first identification of carcinoembryonic antigen, to the discovery of prostate-specific antigen, to numerous others described within, biomarkers of disease are detectable in a plethora of sample types. The growing number of biomarkers for infection, autoimmunity, and cancer allow for increasingly early detection, to identification of novel drug targets, to prognostic indicators of disease outcome. However, more and more studies are finding that a single cytokine or growth factor is insufficient as a true disease biomarker and that a more global perspective is needed to understand true disease biology. Such a broad view requires a multiplexed platform for chemical detection, and antibody arrays meet and exceed this need by performing this detection in a high-throughput fashion. Herein, we will discuss how antibody arrays have evolved, and how they have helped direct new drug target design, helped identify therapeutic disease markers, and helped in earlier disease detection. From asthma to renal disease, and neurological dysfunction to immunologic disorders, antibody arrays afford a bright future for new biomarkers discovery.


Endocannabinoids and the regulation of body fat: the smoke is clearing.
Endocannabinoids, endogenous ligands of cannabinoid receptor type 1 (CB1), have emerged as novel and important regulators of energy homeostasis. A report in this issue demonstrates reduced body weight, fat mass, and appetite in CB1-/- mice. Examination of the underlying mechanisms reveals a dual role for endocannabinoids as they affect both appetite and peripheral lipolysis.


Sequential bacteriological observations in relation to cell-mediated and humoral antibody responses of cattle infected with Mycobacterium paratuberculosis and maintained on normal or high iron intake.
Twenty calves were orally infected with Mycobacterium paratuberculosis before weaning. Ten of these plus 4 non-infected controls were maintained on elevated dietary iron intake from 6 to 33 months of age. During this time, in which the majority of animals were bred, the influence of increased dietary iron upon tests of cellular and humoral immune responsiveness to antigens of the organism were monitored. Results were examined in relation to the organism's capacity to multiply and infect up to 7 portions of the intestinal tract. No significant differences were detected in the degree of intestinal disease or pattern of faecal excretion of M. paratuberculosis in iron supplemented and non-supplemented cattle. Cutaneous delayed-type hypersensitivity (DTH) to johnin PPD developed at 1 month and in-vitro lymphocyte and immunostimulatory activity (LS) to this antigen at 2 months after infection. LS indices were significantly reduced in magnitude in iron-supplemented cattle (p less than 0.01). Most ELISA antibody responses were positive 10 to 17 months after infection and preceded the fewer number of CF responses by several months. Neither of the antibody tests was affected by elevated iron intake. Generally, complete or partial resistance to paratuberculosis was associated with sustained positive monthly LS tests (index greater than or equal to 2.0), whereas antibody levels tended to be sustained only in the more severely affected cattle. Although neither test system was affected by pregnancy the ELISA failed to detect a significant proportion of cattle chronically shedding M. paratuberculosis in faeces.


Impact of glycemic control on oral health status in type 2 diabetes individuals and its association with salivary and plasma levels of chromogranin A.
To evaluate the effect of glycemic control status in type 2 diabetes mellitus (T2DM) individuals on clinical oral health indicators and to compare the concentrations of plasma and salivary chromogranin A (CHGA) among nondiabetic subjects and T2DM patients, exploring their associations. In this cross-sectional study, 32 patients with controlled T2DM, 31 with poorly controlled T2DM and 37 nondiabetic subjects underwent a clinical and periodontal examination. CHGA concentrations were determined in saliva and plasma with ELISA. Poorly controlled T2DM group exhibited significantly higher mean buffering capacity, plaque index and bleeding on probing than other groups (P<0.05). No difference was found to DMFT (decayed, missed and filled teeth) index between groups. Sites with clinical attachment loss (CAL) of 4 and 5-6mm were significantly higher in both diabetic groups compared to control group (P<0.05). Poorly controlled T2DM group had significantly higher sites with CAL ≥ 7 mm than other groups (P=0.001). Significantly higher plasma and salivary CHGA levels were found in T2DM groups (P<0.05). In both diabetic groups, probing depths 5-6mm and CAL 5-6mm were associated with higher salivary CHGA concentration (P<0.05). The findings revealed that T2DM patients were more prone to periodontal tissue damage than to caries risk. The results also provide some evidence that the degree of attachment loss deteriorates significantly with poor glycemic control in T2DM (CAL ≥ 7 mm). Moreover, the results suggest that high concentrations of salivary CHGA are associated with worse periodontal parameters and T2DM, and this could be related to the pathogenesis of both diseases.


Retention loss of reversed-phase chromatographic columns using 100% aqueous mobile phases from fundamental insights to best practice.
This work deals with experimental investigations pertaining to the impact of chemical (electrolyte concentration from 0 to 100 mM, dissolved nitrogen gas from 0 to 6.7 × 10-4 M in water; surface chemistry including hexylphenyl, polyphenyl, C30, C18, and C8; surface coverage in C18-bonded chains from 1.5 to 3.5 µmol/m2; presence of surface dopant), physical (hydrostatic pressure of water from 50 to 500 bar; temperature from 27 ∘C to 75 ∘C), and structural parameters (average pore size from 50 Å to 400 Å; pore connectivity) on the dewetting kinetics of water from the hydrophobic mesopores of particles packed in RPLC columns. The results are explained from physico-chemical viewpoints involving intrusion and extrusion Laplace pressures, advancing and receding contact angles, surface tension of water, vapor pressure of water, 3D reconstruction of the actual mesoporous structure, pore connectivity, and the hysteresis in nitrogen adsorption and desorption isotherm onto reversed-phase chromatographic materials. A model of water dewetting consistent with the observations and the physical interpretations is then proposed. Finally, the most relevant practical solutions (pressurizing the column in absence of flow, pore size enlargement, using phenyl-bonded phase, polar embedded or surface doped C18-bonded phases, reducing the C18 surface coverage, doping the silica surface, lengthening of the alkyl-bonded chains, applying low temperatures, purging and degassing the mobile phase with helium gas) are suggested in order to eliminate or at least minimize the retention loss of RPLC columns when using fully aqueous mobile phases.


Deepwater Horizon 2010: Subsea dispersants protected responders from VOC exposure.
Controversy remains on the use of Sub-Sea Dispersant Injection (SSDI) during the Deepwater Horizon (DWH) spill to minimize the exposure of responders on surface vessels to volatile organic compounds (VOC). Here, we use extensive evidence (>90,000 VOC measurements) collected near the oil well MC252 site during the DWH spill and demonstrate at a high level of statistical confidence that SSDI enhanced the safety and health conditions of the responders at the water surface through the reduction of airborne VOC concentrations in a dose-dependent manner. VOC levels on ships' decks were clearly diminished (p < 0.001) during subsea dispersant use, and incidents of peak concentrations (>50 ppm VOC) that could have been an immediate concern to worker health were reduced by a factor of ~6 to 19 when dispersants were delivered at the intended rate. SSDI thus played an important role in minimizing potential exposure to VOC, and should be embedded in guidelines and regulations for dispersant use.


Significant dose reduction using synchrotron radiation computed tomography: first clinical case and application to high resolution CT exams.
Since the invention of Computed Tomography (CT), many technological advances emerged to improve the image sensitivity and resolution. However, no new source types were developed for clinical use. In this study, for the first time, coherent monochromatic X-rays from a synchrotron radiation source were used to acquire 3D CTs on patients. The aim of this work was to evaluate the clinical potential of the images acquired using Synchrotron Radiation CT (SRCT). SRCTs were acquired using monochromatic X-rays tuned at 80 keV (0.350 × 0.350 × 2 mm3 voxel size). A quantitative image quality comparison study was carried out on phantoms between a state of the art clinical CT and SRCT images. Dedicated iterative algorithms were developed to optimize the image quality and further reduce the delivered dose by a factor of 12 while keeping a better image quality than the one obtained with a clinical CT scanner. We finally show in this paper the very first SRCT results of one patient who received Synchrotron Radiotherapy in an ongoing clinical trial. This demonstrates the potential of the technique in terms of image quality improvement at a reduced radiation dose for inner ear visualization.


The atopic dermatitis-like lesion and the associated MRSA infection and barrier dysfunction can be alleviated by 2,4-dimethoxy-6-methylbenzene-1,3-diol from Antrodia camphorata.
Atopic dermatitis (AD) is an inflammatory skin disease with an associated barrier dysfunction and Staphylococcus aureus infection. The mainstay steroid and calcineurin inhibitor therapy shows some adverse effects. 2,4-Dimethoxy-6-methylbenzene-1,3-diol (DMD) is a benzenoid isolated from Antrodia camphorata. We investigated the inhibitory effect of DMD on methicillin-resistant S. aureus (MRSA), the chemokine production in stimulated keratinocytes, and the AD-like lesion found in ovalbumin (OVA)-sensitized mice. The antimicrobial effect and cutaneous barrier function were evaluated using an in vitro culture model and an in vivo mouse model of AD-like skin. DMD exhibited a comparative minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against MRSA with nalidixic acid, a conventional antibiotic. The MIC and MBC for DMD was 78.1 and 156.3 μg/ml, respectively. DMD also showed the ability to eliminate the clinical bacteria isolates with resistance to methicillin and vancomycin. The DNA polymerase and gyrase inhibition evoked by DMD for bacterial lethality was proposed. In the activated keratinocytes, DMD stopped the upregulation of chemokines (CCL5 and CCL17) and increased the expression of differentiation proteins (filaggrin, involucrin, and integrin β-1). Topical application of DMD facilely penetrated into the skin, with AD-like skin displaying 2.5-fold greater permeation than healthy skin. The in vivo assessment using the mouse model with OVA sensitization and MRSA inoculation revealed a reduction of transepidermal water loss (TEWL) and bacterial burden by DMD by about 2- and 100-fold, respectively. Differentiation proteins were also restored after topical DMD delivery. Our data demonstrated an advanced concept of AD treatment by combined barrier repair and bacterial eradication with a sole agent for ameliorating the overall complications.


Effects of light-emitting diode spectra on the vertebrate ancient long opsin and gonadotropin hormone in the goldfish Carassius auratus.
We determined the molecular mechanism underlying the environmental (photoperiodic) regulation of sexual maturation in fish, we examined the expression of sexual maturation-related hormones and vertebrate ancient long opsin (VAL-opsin) in goldfish (Carassius auratus) exposed to different light spectra (red and green light-emitting diodes). We further evaluated the effect of exogenous gonadotropin hormone (GTH) on the expression of VAL-opsin under different light conditions. Our results demonstrated that the expression of GTHs was higher in the fish exposed to green light, and VAL-opsin levels were increased in the fish receiving GTH injection. Therefore, we have uncovered a molecular mechanism underlying the environmental (light)-induced trigger for sexual maturation: VAL-opsin is activated by green light and GTH, which promotes the expression of sexual maturation genes.


Dexamethasone enhances serum deprivation-induced necrotic death of rat C6 glioma cells through activation of glucocorticoid receptors.
Glucocorticoids have been shown to be neurotoxic and appear to play a role in neuronal cell loss during aging and following neuropathological insults. However, very little is known about the effects of these steroid hormones on glial cells. The effect of the synthetic glucocorticoid dexamethasone (DEX) on glial cell viability was therefore examined by measuring neutral red uptake into rat C6 glioma cells. Serum deprivation markedly reduced cell viability, and this effect was significantly enhanced by DEX. Electrophoretic analysis showed that the cell damage induced by either serum deprivation alone or in combination with DEX was not accompanied by the degradation of DNA into nucleosomic fragments. Electron microscopic studies confirmed that serum deprivation and glucocorticoid treatment caused necrotic cell death. Furthermore, the effect of DEX on cell viability could be mimicked by the glucocorticoid receptor agonist RU28362, and completely prevented by the glucocorticoid receptor antagonist RU38486. These results indicate that dexamethasone can enhance the necrotic death of glioma cells induced by serum deprivation, suggesting that glucocorticoids may be involved in the chronic alteration of brain function arising from neuropathological damage to glial cells.


Intermediate domain of receptor-interacting protein kinase 1 (RIPK1) determines switch between necroptosis and RIPK1 kinase-dependent apoptosis.
Receptor-interacting protein kinase 1 (RIPK1) is an important component of the tumor necrosis factor receptor 1 (TNFR1) signaling pathway. Depending on the cell type and conditions, RIPK1 mediates MAPK and NF-κB activation as well as cell death. Using a mutant form of RIPK1 (RIPK1ΔID) lacking the intermediate domain (ID), we confirm the requirement of this domain for activation of these signaling events. Moreover, expression of RIPK1ΔID resulted in enhanced recruitment of caspase-8 to the TNFR1 complex II component Fas-associated death domain (FADD), which allowed a shift from TNF-induced necroptosis to apoptosis in L929 cells. Addition of the RIPK1 kinase inhibitor necrostatin-1 strongly reduced recruitment of RIPK1 and caspase-8 to FADD and subsequent apoptosis, indicating a role for RIPK1 kinase activity in apoptotic complex formation. Our study shows that RIPK1 has an anti-apoptotic function residing in its ID and demonstrates a cellular system as an elegant genetic model for RIPK1 kinase-dependent apoptosis that, in contrast to the Smac mimetic model, does not rely on depletion of cellular inhibitor of apoptosis protein 1 and 2 (cIAP1/2).


Controversies in Osteoporosis Treatment of Nursing Home Residents.
Osteoporotic fractures are a common and serious health problem for older adults living in nursing homes (NHs). Risk of fracture increases with age and dementia status, yet gaps in evidence result in controversies around when to start and stop treatment for osteoporosis in NH residents, particularly those who have high fracture risk but have limited life expectancy. In this article, we discuss these areas of controversy. We provide an overview of current guidelines that explicitly address osteoporosis treatment strategies for NH residents, review the evidence for osteoporosis medications in NH residents, and use these sources to suggest practical recommendations for clinical practice and for research. Three published guidelines (from the United States, Canada, and Australia) and several studies provide the current basis for clinical decisions about osteoporosis treatment for NH residents. Practical approaches may include broad use of vitamin D and selective use of osteoporosis medication based on risks, benefits, and goals of care. Clinicians still lack strong evidence to guide treatment of NH residents with advanced dementia, multimorbidity, or severe mobility impairment. Future priorities for research include identifying optimal approaches to risk stratification and prevention strategies for NH residents and evaluating the risk-benefit profile of pharmacologic treatments for osteoporosis NH residents across key clinical strata. In the absence of such evidence, decisions for initiating and continuing treatment should reflect a patient-centered approach that incorporates life expectancy, goals of care, and the potential burden of treatment.