Valve turning towards on-cycle in cobalt-catalyzed Negishi-type cross-coupling.
Ligands and additives are often utilized to stabilize low-valent catalytic metal species experimentally, while their role in suppressing metal deposition has been less studied. Herein, an on-cycle mechanism is reported for CoCl2bpy2 catalyzed Negishi-type cross-coupling. A full catalytic cycle of this kind of reaction was elucidated by multiple spectroscopic studies. The solvent and ligand were found to be essential for the generation of catalytic active Co(I) species, among which acetonitrile and bipyridine ligand are resistant to the disproportionation events of Co(I). Investigations, based on Quick-X-Ray Absorption Fine Structure (Q-XAFS) spectroscopy, Electron Paramagnetic Resonance (EPR), IR allied with DFT calculations, allow comprehensive mechanistic insights that establish the structural information of the catalytic active cobalt species along with the whole catalytic Co(I)/Co(III) cycle. Moreover, the acetonitrile and bipyridine system can be further extended to the acylation, allylation, and benzylation of aryl zinc reagents, which present a broad substrate scope with a catalytic amount of Co salt. Overall, this work provides a basic mechanistic perspective for designing cobalt-catalyzed cross-coupling reactions.


Comment on "Drosophila dosage compensation involves enhanced Pol II recruitment to male X-linked promoters".
Conrad et al. (Reports, 10 August 2012, p. 742) reported a doubling of RNA polymerase II (Pol II) occupancy at X-linked promoters to support 5' recruitment as the key mechanism for dosage compensation in Drosophila. However, they employed an erroneous data-processing step, overestimating Pol II differences. Reanalysis of the data fails to support the authors' model for dosage compensation.


Are GM Crops for Yield and Resilience Possible?
Crop yield improvements need to accelerate to avoid future food insecurity. Outside Europe, genetically modified (GM) crops for herbicide- and insect-resistance have been transformative in agriculture; other traits have also come to market. However, GM of yield potential and stress resilience has yet to impact on food security. Genes have been identified for yield such as grain number, size, leaf growth, resource allocation, and signaling for drought tolerance, but there is only one commercialized drought-tolerant GM variety. For GM and genome editing to impact on yield and resilience there is a need to understand yield-determining processes in a cell and developmental context combined with evaluation in the grower environment. We highlight a sugar signaling mechanism as a paradigm for this approach.


Utilization, benefits, and impact of an e-consultation service across diverse specialties and primary care providers.
Access to specialist advice remains a barrier for primary care providers (PCPs) and their patients. Virtual consultations have been used to expedite access. There are few studies demonstrating the utilization and impact of such services. We established a regional e-consultation service that was used across a wide range of specialty services and PCPs. We prospectively collected all e-consultations submitted from April 1, 2011 to June 30, 2012. Utilization data collected included number of e-consultations submitted, specialist response, and time required for the specialist to complete the e-consultation. Perceived benefit to the PCPs and their patients and the impact on care delivery were determined from a close-out survey. Fifty-nine PCPs submitted 406 e-consultations to 16 specialty services. The specialist provided an answer without requesting further information in 89% of cases, with >90% of cases taking <15 min for the specialist to complete. Seventy-five percent of cases were answered in <3 days. The service was perceived as highly beneficial to providers and patients in>90% of cases. In 43% of submitted cases a traditional referral was originally contemplated but was now avoided. We successfully implemented an e-consultation service across diverse PCPs and specialty services that was highly valued. Almost half of referrals submitted would have required a face-to-face consultation if the service had not been available. Thus e-consultation has tremendous potential for improving access to specialist advice in a much more timely manner than the traditional referral-consultation process.


Termites of a South African savanna : II. Densities and populations of smaller mounds, and seasonality of breeding.
The commonest epigeal termite mounds at Nylsvley Reserve, northern Transvaal, are constructed by Cubitermes pretorianus and shared by other termites and by ants. Two surveyed areas had the equivalents of 385 and 496 mounds ha-1 (328 and 432 ha-1 respectively with live Cubitermes). Counts of all termite species and stages in 13 mounds are given. Nests contained up to 15,000 Cubitermes workers (of which up to 0.7% were parasitised by nematodes). Egg-laying was seasonal, with a peak early in the wet season and few eggs in the nest in late autumn (and hence few larvae in winter). Soldier production showed two peaks per year, one at swarming and one in mid-dry season. Aganotermes workers sharing the mounds showed seasonal (over winter) abdominal storage of food reserves. Counts of populations and stored forage in two small Trinervitermes rhodesiensis mounds are also given.


Isolation and characterization of Patnopecten mid-gut gland endo-beta-xylosidase active on peptidochondroitin sulfate.
An endo-beta-xylosidase acting on the linkage region of peptidochondroitin sulfate was isolated from the mid-gut gland of the mollusc Patnopecten and purified about 375-fold, using a combination of ammonium sulfate fractionation, gel filtration on Sephacryl S-200, and DEAE-Sephacel chromatography. The pH optimum and the isoelectric point of this enzyme were 4.0 and 7.0, respectively. The molecular weight, estimated by gel filtration through Sephacryl S-200, was 78,000. The purified enzyme was completely free from protease, exoglycosidases, sulfatase, and phosphatase. This enzyme hydrolyzed the xylosyl serine linkage of the linkage region of various glycosaminoglycans, that is chondroitin sulfate, dermatan sulfate and heparan sulfate, all possessing a very small peptide segment, but not proteoglycans. It was concluded that this endo-beta-xylosidase was involved in the catabolism of proteoglycans.


Effect of (R)-salbutamol on the switch of phenotype and metabolic pattern in LPS-induced macrophage cells.
Evidence demonstrates that M1 macrophage polarization promotes inflammatory disease. Here, we discovered that (R)-salbutamol, a β2 receptor agonist, inhibits and reprograms the cellular metabolism of RAW264.7 macrophages. (R)-salbutamol significantly inhibited LPS-induced M1 macrophage polarization and downregulated expressions of typical M1 macrophage cytokines, including monocyte chemotactic protein-1 (MCP-1), interleukin-1β (IL-1β) and tumour necrosis factor α (TNF-α). Also, (R)-salbutamol significantly decreased the production of inducible nitric oxide synthase (iNOS), nitric oxide (NO) and reactive oxygen species (ROS), while increasing the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio. In contrast, (S)-salbutamol increased the production of NO and ROS. Bioenergetic profiles showed that (R)-salbutamol significantly reduced aerobic glycolysis and enhanced mitochondrial respiration. Untargeted metabolomics analysis demonstrated that (R)-salbutamol modulated metabolic pathways, of which three metabolic pathways, namely, (a) phenylalanine metabolism, (b) the pentose phosphate pathway and (c) glycerophospholipid metabolism were the most noticeably impacted pathways. The effects of (R)-salbutamol on M1 polarization were inhibited by a specific β2 receptor antagonist, ICI-118551. These findings demonstrated that (R)-salbutamol inhibits the M1 phenotype by downregulating aerobic glycolysis and glycerophospholipid metabolism, which may propose (R)-salbutamol as the major pharmacologically active component of racemic salbutamol for the treatment of inflammatory diseases and highlight the medicinal value of (R)-salbutamol.


Developing a Checklist: Consensus Via a Modified Delphi Technique.
To create a universal checklist of key preparatory steps to aid anesthesiologists in patient separation from cardiopulmonary bypass. Multistep, iterative survey with statistically guided refinement of survey items using a modified Delphi technique. Internet-based surveys. Ninety active members of the Society of Cardiovascular Anesthesiologists volunteered to participate, including geographically distributed private practice and academic physicians. A series of checklist items was created and distributed to 90 anesthesiologists, who assessed each item's importance in preparing for patient separation from cardiopulmonary bypass and added, deleted, or modified any items as they saw fit. Items meeting a threshold of greater than 90% group acceptance were carried forward to a second survey. These items then were evaluated using a 5-point Likert scale to grade relative importance and then compared with the group's responses, creating a third survey with refined checklist items. The results then were used to generate a final survey based on each item achieving certain predefined statistical criteria, which then were scored again by the participants, generating a final checklist via statistically guided consensus. An initial checklist containing 28 possible items was proposed to the participants. After the iterative process was completed, a final checklist of 10 items deemed essential to prepare for bypass separation was created. A checklist to aid in bypass separation was created with key steps derived from a statistically driven Delphi process. This technique of iterative consensus building may be useful in developing additional safety checklists.


Follow-up after polypectomy of colorectal adenomas. The importance of total colonoscopy.
Five hundred eighty-two patients with colorectal adenomas or early cancers were polypectomized from 1974 to 1985. In 100 patients, total colonoscopy was performed more than twice after the initial polypectomies. These patients were divided into three groups: group A patients underwent total colonoscopy at 1-year intervals; group B patients underwent total colonoscopy at 2-year intervals, group C patients underwent total colonoscopy at 3-year or more than 3-year intervals. The frequency and location of newly developed adenomas were investigated. The detection rate for new adenomas was 13% in group A and 50% in group B; thus, there was a significant difference between group A and group B (P less than 0.01). The transverse colon is the only segment where the topological proportion of newly developed adenomas increased in comparison with that of index adenomas (P less than 0.05). The detection rate for new adenomas was significantly higher in patients who had carcinoma in situ at the time of initial polypectomy (P less than 0.05). Questionnaires about colonoscopy and colonic adenomas were therefore mailed to the patients who were lost to follow-up after the polypectomy.


Combating relapsed and refractory Mantle cell lymphoma with novel therapeutic armamentarium: Recent advances and clinical prospects.
Mantle cell lymphoma (MCL) is a rare, aggressive subtype of non-Hodgkin's lymphoma (NHL), accounting for 5% of all cases. Due to its virulence factor, it is an incurable disease and keeps relapsing despite an intensive treatment regimen. Advancements in research and drug discovery have shifted the treatment strategy from conventional chemotherapy to targeted agents and immunotherapies. The establishment of the role of Bruton tyrosine kinase led to the development of ibrutinib, a first-generation BTK inhibitor, and its successors. A conditioning regimen based immunotherapeutic agent like ibritumumob, has also demonstrated a viable response with a favorable toxicity profile. Brexucabtagene Autoleucel, the only approved CAR T-cell therapy, has proven advantageous for relapsed/refractory MCL in both children and adults. This article reviews certain therapies that could help update the current approach and summarizes a few miscellaneous agents, which, seldom studied in trials, could alleviate the regression observed in traditional therapies. DATA AVAILABILITY: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.


Increased expression of dihydrodiol dehydrogenase induces resistance to cisplatin in human ovarian carcinoma cells.
We employed cDNA microarrays to identify the differentially expressed genes in a cisplatin-sensitive parental (2008) human ovarian carcinoma cell line and its cisplatin-resistant variant (2008/C13*). Differential expression of five genes was found in the 2008/C13* cells, a result confirmed by semi-quantitative reverse transcription-PCR. The five genes were identified as fibroblast muscle-type tropomyosin and skeletal muscle-type tropomyosin, dihydrodiol dehydrogenase, apolipoprotein J and glucose-6-phosphate dehydrogenase variant-A. Treatment of the 2008 cells with cisplatin (at its IC(50) concentration of 2 microm) induced expression of these genes, as determined by semi-quantitative reverse transcription-PCR analysis using gene-specific primers. In contrast, treatment of the drug-resistant 2008/C13* cells with cisplatin (at its IC(50) concentration of 20 microm) did not lead to the induction of any of the aforementioned genes. Most importantly, constitutive overexpression of dihydrodiol dehydrogenase (but not the other genes) in the 2008 cells led to induction of cisplatin resistance, clearly indicating its role in the development of the resistance phenotype in the 2008/C13* cells. The development of cisplatin resistance in the transfected cells was associated with an increase in the dihydrodiol dehydrogenase enzyme activity. Although at present it is not clear how dihydrodiol dehydrogenase is involved in cisplatin resistance, the identification of this gene as a causal factor suggests the existence of a hitherto undefined pathway resulting in cisplatin resistance.


A paradox in the interaction of the gravitational and electromagnetic fields ?
The assumption that the extent of the interaction of the electromagnetic and gravitational fields is fundamentally dependent on the frequency of the electromagnetic field is consistent with data on the deflexion of radiation by massive bodies.


A novel apoptotic pathway as defined by lectin cellular initiation.
In this study of lectin-induced apoptosis we found that wheat germ agglutinin (WGA) initiated an accelerated type of programmed cell death developing after only 30 min of incubation with tumor cells. To analyze possible mechanisms, studies were focused using the WGA lectin whose carbohydrate specificity is well defined. We found that WGA could induce apoptosis by binding to either N-acetylneuraminic acid or N-acetylglucosamine (GlcNAc) on the cell surface of normal and malignant cells. We also showed that it is unlikely that WGA triggers apoptosis by binding to the carbohydrate portion of Fas. CrmA gene transfection did not inhibit WGA-mediated apoptosis of Jurkat cells. In addition, Jurkat-R cells selected for resistance to Fas signaled apoptosis manifested high sensitivity to WGA as did Fas-negative BL6 melanoma cells. WGA-induced apoptosis is also caspase-3-independent and was found to be triggered via a mitochondrial pathway. WGA induced a loss of transmembrane potential, disruption of the inner mitochondria membrane, and release of cytochrome c and caspase-9 activation after 30 min of cell interaction. Interestingly, Bcl-2 gene transfection did not affect sensitivity of Jurkat cells to WGA. The Jurkat-R subline that has been shown to be Bax and Bak deficient and resistant to various apoptotic signals was highly sensitive to WGA-induced apoptosis. In summary, WGA triggers a unique pattern of apoptosis that is extremely fast, Fas- and caspase-3-independent, and is mediated via a mitochondrial pathway. However, its mitochondrial component is unrestrained by the loss of Bax and Bak or the upregulation of Bcl-2 expression.


Does spinal fusion influence lateral oscillations in scoliosis patients? Unstable equilibrium analysis.
Patients with Idiopathic Scoliosis demonstrate vestibular and proprioceptive system perturbations. Scoliosis can be treated through spinal fusion. Does spinal fusion present significant effect of dynamic equilibrium in case of lateral oscillations? Using an unstable platform in frontal plane, dynamic equilibrium in patients with idiopathic scoliosis (before and one year after spinal fusion) was analyzed against a population of asymptomatic subjects. A significant group effect was observed on Center of Mass in case of Eyes Opened. In relation to sensory integration, spinal fusion coupled to rehabilitation program is associated to better dynamic equilibrium.


Dynamin recruitment by clathrin coats: a physical step?
Recent structural findings have shown that dynamin, a cytosol protein playing a key-role in clathrin-mediated endocytosis, inserts partly within the lipid bilayer and tends to self-assemble around lipid tubules. Taking into account these observations, we make the hypothesis that individual membrane-inserted dynamins imprint a local cylindrical curvature to the membrane. This imprint may give rise to long-range mechanical forces mediated by the elasticity of the membrane. Calculating the resulting many-body interaction between a collection of inserted dynamins and a membrane bud, we find a regime in which the dynamins are elastically recruited by the bud to form a collar around its neck, which is reminiscent of the actual process preempting vesicle scission. This physical mechanism might therefore be implied in the recruitment of dynamins by clathrin coats.


The effect of photoactivation time and light tip distance on the degree of conversion of light and dual-cured dentin adhesives.
The degree of conversion of dental adhesive is an important parameter since poor mechanical properties are related to low percentage of monomer-to-polymer conversion within resin-based materials. To evaluate the influence of polymerization time and light guide distance on the degree of conversion (DC) of three contemporary dental adhesives. The spectral data of ExciTE DSC, Single Bond ® , and Adper ® Prompt L-Pop were analyzed using FTIR spectroscopy after 20 s, 40 s, and 60 s of photoactivation times. Light tip distances were kept at 1, 3, and 6 mm during the exposures. Data were analyzed using ANOVA and Tukey's test (α = 0.05). Within groups, greater DC values were found using a tip distance of 1 mm or a 60-s curing time for Single Bond ® (59%) and Adper ® Prompt L-Pop (65%). No statistically significant difference (P > 0.05) was found using either 1 mm or 3 mm tip distances after 20 s, 40 s, and 60 s of light curing time for Single Bond ® . ExciTE ® DSC showed the greatest DC values with light tip distances of 1 mm (90%) and 3 mm (89%), using 60 s of light curing. The self-etch adhesive Adper ® Prompt L-Pop could be applied in shallow cavity preparations and must be light cured for at least 40 s. The light-cured total-etch adhesive ExciTE ® DSC could be applied in every restorative scenario if the curing time is extended up to 60 s or if the tip distance is extended up to 3 mm.


Ontogenetic development of the oral apparatus and oropharyngeal cavity in bullfrog tadpoles (Lithobates catesbeianus, Shaw 1802).
The present study aimed to describe the morphology of oral apparatus and oral cavity of bullfrog tadpoles during their development and metamorphosis. The oral apparatus and oropharyngeal cavity of tadpoles from hatching up to metamorphosis stage was dissected for further analysis. These structures were fixed in Karnovsky solution, afterwards in osmium tetroxide and metalized in palladium gold and electron-micrographed using the scanning electron microscope. The development of oral apparatus started with the formation and keratinization of the jaw sheaths and labial teeth followed by the formation of marginal and sub-marginal papillae. Degeneration of oral apparatus and formation of mouth was observed during metamorphosis. From stage-42 (metamorphic climax) to stage-43, the jaw sheath and labial tooth rows were disappeared progressively while the size and number of labial papillae were decreased. At stage-44, mouth formation started with the development of anterior and posterior labium though the labial papillae were still present. At stage-45 and 46, mouth was already formed, being very similar to the adult and characterized by the progressive increase in size. The sequence of events that happen during the development of oral apparatus of Lithobates catesbeianus Shaw, 1802 tadpoles follows the same pattern as occur in other anuran species but metamorphic atrophy of the oral apparatus follows the sequence of morphogenesis.


Protocol to isolate live single cells while retaining spatial information by combining cell photolabeling and FACS.
Single-cell techniques have revolutionized biology; however, the required sample processing inherently implies the loss of spatial localization. Here, using an approach called photoconversion of areas to dissect micro-environments (PADME), we detail steps to isolate live single cells from a primary breast tumor while retaining spatial information by combining cell photolabeling and FACS (fluorescence-activated cell sorting). These live cells can be subsequently used for myriad techniques, from flow cytometry to single-cell RNA sequencing or other single cell "omics" approach. For complete details on the use and execution of this protocol, please refer to Baldominos et al. (2022).


Testicular adrenal rest tumors develop independently of long-term disease control: a longitudinal analysis of 50 adult men with congenital adrenal hyperplasia due to classic 21-hydroxylase deficiency.
Testicular adrenal rest tumors (TARTs) and hypogonadotropic hypogonadism are the two most common causes for male infertility in classic 21-hydroxylase deficiency. Current hypotheses suggest the quality of disease control to be one of the main pathogenic factors for TART development. The aim was to study long-term predictors for TART development in a retrospective longitudinal study. Fifty men with classic 21-hydroxylase deficiency (31 salt wasting, 19 simple virilizing) were investigated. Testicular ultrasound at a median age at investigation of 27 years detected TARTs in 28 of 50 subjects (19 salt wasting, 9 simple virilizing). TART presence was correlated with long-term parameters of disease control during childhood and adolescence obtained from patients' charts: 24-hour urine pregnanetriol, serum 17-hydroxyprogesterone, onset and stage of pubic hair development, testicular growth, and bone age in relation to chronological age. There was no difference in pregnanetriol excretion over lifetime between patients with and without TARTs. Similarly, neither development of pubic hair and testicular volume (Tanner) nor bone age in relation to chronological age differed between the two groups. Furthermore, the two groups had the same body mass index and the same impairment of final height in relation to midparental target height. Our longitudinal analysis demonstrates no association between TART presence and parameters of disease control. These data, therefore, argue for other mechanisms more relevant for TART induction including those occurring during fetal development.


Testosterone Deficiency is Not Protective Against the Development of Adenocarcinoma of the Prostate in a Type 1 Diabetic Patient.
We present a case of prostate cancer (PC) developing in a hypogonadal patient with well-controlled type 1 diabetes. The purpose of reporting this case is to emphasize that regular prostate examinations and prostate-specific antigen (PSA) measurements should be preformed in the diabetic male, even though the incidence of PC is lower in this group of patients. In addition, these examinations and tests need to be preformed even in the hypogonadal patient with diabetes since the presence of a low serum testosterone (T) level does not preclude the development of PC. This is because the development of PC is not related to serum androgen levels but to the androgen levels within the prostate, and dihydrotestosterone (DHT) levels and not T levels within the prostate gland are responsible for the development of PC. In the hypogonadal male, intraprostatic DHT may be high since DHT can be formed from adrenal androgens, particularly androstenedione, through activation of 5α-reductase 2, which is the minority enzyme in the normal prostate but becomes the major enzyme in the formation and growth of PC.


Influence of COVID-19 outbreak on emergency department Press Ganey scores of emergency physicians.
The authors investigate whether there is a difference in Press Ganey (PG; patient satisfaction scores) scores for the emergency physicians before and during the coronavirus disease 2019 (COVID-19) outbreak at a regional group of emergency departments in the southeastern United States. The authors hypothesize that decreases in emergency department volume, less emergency department boarding of admissions, reduced use of hallway beds, and favorable attitudes toward emergency physicians during the COVID-19 outbreak may influence patient satisfaction scores measured in the Press Ganey surveys. The authors performed a retrospective review of PG scores obtained over the prior 7 months at 8 larger teaching hospitals in the Southeast region (Florida, Georgia, and South Carolina). Averaged physician PG Scores and their 4 components-courtesy, time to listen, informative regarding treatment, concern for comfort-were collected. The authors evaluated the overall physician PG ratings for March through May 2020 (COVID outbreak) vs the prior 4 months. Overall emergency physician scores, using top box methodology of percent highest response, were averaged from 4 questions regarding the emergency physician's care. There were 6272 patient satisfaction surveys returned in the 7-month study period; 4003 responses during the pre-COVID months (November 2019-February 2020) and 2296 during the COVID months (March through May 2020). Results showed that in the "pre-COVID time" the PG surveys scored in the 17% of all PGs in the country (63.9% "top-box" or highest rating score) as compared to scoring in the 34% of all PGs (68.1% "top-box") during "COVID time." These data were statistically significant using a chi-square analysis with P < 0.001. Emergency physician patient satisfaction scores, as represented by the PG score, were significantly higher during the COVID months, in comparison to the pre-COVID months, for 8 teaching hospitals in the Southeast region of the United States.


Evaluation of Multimodality Management of Adenoid Cystic Carcinoma of the Head and Neck.
Adenoid cystic carcinoma is a relatively rare tumour arising from salivary glands of head and neck region. Surgery and radiotherapy form standard treatment modalities in the management of this tumor. In this analysis we present results of multimodality treatment in our cohort of patient. This retrospective analysis evaluated results of treatment in forty patients diagnosed with adenoid cystic carcinoma of the head and neck. Evaluation was done to identify prognostic factors affecting the disease free survival. A median disease free survival of 34 ± 2.42 (Median ± SE) versus 10 ± 5.45 months was seen in patients undergoing surgery followed by post operative radiotherapy versus radiotherapy alone (P = 0.01). A radiotherapy dose more than 60 Gy was associated with a better disease free survival compared with patients receiving less than 60 Gy (P = 0.01). Positive surgical margins and perineural invasion were associated with a poor treatment outcome (P = 0.02) Patients with c-kit positive status showed a poor local control rate (P = 0.05).


Gold-conductive polymer nanoparticles: a hybrid material with enhanced photonic reactivity to environmental stimuli.
We have designed a simple synthetic procedure to encapsulate colloidal gold nanoparticles by electrostatic adsorption with water-soluble poly(aniline-2-carboxylic acid). The composite nanoparticles are stable in aqueous buffer and retain the respective optical reactivity of the gold colloid to refractive index increases, and of the conductive polymer to pH changes and oxidoreduction. The new composite displays, however, significant enhancements in photonic performance when compared to the individual components, which seem to result from electronic interplay between the two materials in the hybrid structure. The enhanced photonic reactivity of the composite structure offers new opportunities for biosensing application.


Use of a synthetic hybrid-scale fiber matrix in the management of chronic and complex wounds: a retrospective case series.
Chronic and complex wounds are often recalcitrant to treatment, regardless of etiology. These wounds are a burden to both the patient and the health care system. Advanced treatment options are needed to improve patient outcomes. An SHSFM has shown positive results in the management of complex and chronic wounds. In this retrospective case series, patients with chronic and complex wounds of various etiologies were treated with the SHSFM to assess its utility in the management of these wound types. A retrospective review of the charts of 18 patients with a total of 28 wounds was conducted. Healing was monitored at follow-up visits, and the SHSFM was reapplied as clinically indicated. The average patient age was 59 years, and average initial wound surface area was 43.4 cm2. Wound types included ulcers, surgical and traumatic wounds, necrotic infections, and others. Complete healing was achieved in 89% of wounds. The average time to healing was 196 days ± 146.7 standard deviation, and the number of applications per wound ranged from 1 to 11. This case series demonstrates the unique versatility of the SHSFM in achieving appropriate clinical outcomes depending on wound and patient factors.


Associations With Severe Desaturation Events Among Children Receiving Noninvasive Respiratory Support at Time of Intubation.
Endotracheal intubation is a common procedure associated with adverse events, including severe desaturation. Many patients receive noninvasive respiratory support to reduce the need for intubation. There are minimal data about the association between noninvasive respiratory support and the risk of a severe desaturation event during intubation. We aim to differentiate patients based on the level of noninvasive respiratory support, analyze the severe desaturation event by groups, and identify modifiable risk factors. Oral intubations, excluding tube exchanges or re-intubation after unplanned extubation, from October 2018 through July 2020, at the study site were reviewed. A severe desaturation event was defined as [Formula: see text] < 70% or a >15% decrease from baseline in cyanotic heart disease. We analyzed outcomes by 4 groups: room air/nasal cannula (≤0.5 L/kg/min), high-flow nasal cannula (HFNC) (0.5-2 L/kg/min), high HFNC (≥2 L/kg/min), and noninvasive ventilation (NIV). Of 243 subjects who were intubated, 31% were receiving room air/nasal cannula, 25% were receiving HFNC, 18% were receiving high HFNC, and 26% were receiving NIV. Twelve percent of all the subjects had a severe desaturation event. In a univariate analysis, the incidence of a severe desaturation event was similar among all levels of respiratory support (P = .14). A severe desaturation event was more likely in those subjects who were receiving [Formula: see text] ≥ 0.6 at the time of the decision to intubate (19.6%) versus [Formula: see text] < 0.6 (8.1%) (P = .02). The duration of noninvasive respiratory support was longer (5 vs 1 h; P = .02) among those with a severe desaturation event. In a regression analysis, when adjusting for ≥2 intubation attempts pre-intubation, NIV use was independently associated with increased odds of severe desaturation events (odds ratio 3.14, CI 1.08-10.5). Results of our study suggest that [Formula: see text] > 0.60, the duration of noninvasive respiratory support, and exposure to NIV before an intubation are risk factors of severe desaturation events during intubation.


Loss of p53 and altered miR15-a/16-1MCL-1 pathway in CLL: insights from TCL1-Tg:p53(-/-) mouse model and primary human leukemia cells.
Chronic lymphocytic leukemia (CLL) patients with deletion of chromosome 17p, where the p53 gene is located, often develop more aggressive disease with poor clinical outcomes. To investigate the underlying mechanisms for the highly malignant phenotype of 17p- CLL and to facilitate in vivo evaluation of potential drugs against CLL with p53 deletion, we have generated a mouse model with TCL1-Tg:p53(-/-) genotype. These mice develop B-cell leukemia at an early age with an early appearance of CD5+ / IgM+ B cells in the peritoneal cavity and spleen, and exhibit an aggressive path of disease development and drug resistance phenotype similar to human CLL with 17p deletion. The TCL1-Tg:p53(-/-) leukemia cells exhibit higher survival capacity and are more drug resistant than the leukemia cells from TCL1-Tg:p53wt mice. Analysis of microRNA expression reveals that p53 deletion resulted in a decrease of miR-15a and miR-16-1, leading to an elevated expression of Mcl-1. Primary leukemia cells from CLL patients with 17p deletion also show a decrease in miR-15a/miR-16-1 and an increase in Mcl-1. Our study suggests that the p53/miR15a/16-1/Mcl-1 axis may be an important pathway that regulates Mcl-1 expression and contributes to drug resistance and aggressive phenotype in CLL cells with loss of p53.


Preparation of Mitotic Chromosomes with the Squash Technique.
Plant chromosomes are usually obtained from meristematic tissue of active root tips through the conventional squash method. Nevertheless, cytogenetic work usually implies a great effort and some modifications of standard procedures need to be evaluated. In this chapter, we describe our outline for handling chromosomes using the squash method. By using these protocols, high-quality chromosome spreads are obtained, which allow chromosome counting, building karyotypes, and assessing chromosomal landmarks, and enable genome mapping by fluorochrome banding and in situ hybridization techniques.


Novel milrinone analogs of pyridine-3-carbonitrile derivatives as promising cardiotonic agents.
In an attempt to design new inotropic drugs for congestive heart failure (CHF) with less proarrhythmic potential, three series of compounds analogous to milrinone were prepared, namely, 4-aryl-6-(4-pyridyl)-2-oxo-1,2-dihydropyridine-3-carbonitriles 2a-g, 4-aryl-6-(4-pyridyl)-2-thioxo-1,2-dihydropyridine-3-carbonitriles 3a-g and 2-amino-4-aryl-6-(4-pyridyl)-pyridine-3-carbonitriles 4a-g. The first series was prepared by reacting 4-acetyl pyridine with the appropriate aldehyde, ethyl cyanoacetate and ammonium acetate in ethanol. Reaction of 2a-g with phosphorus pentasulfide afforded the second series 3a-g. The third target compounds 4a-g were prepared applying the same procedure used to synthesize 2a-g using malononitrile instead of ethyl cyanoacetate. All the newly synthesized compounds were evaluated for their cardiotonic activity and their in vivo cardiovascular effects. In addition, their oral and parenteral acute toxicity were determined. Compounds 2a, 2b, 2c, 4c and 4f proved to exert cardiotonic activity comparable to that of milrinone using spontaneously beating atria model from reserpine-treated guinea pigs. In addition these compounds proved to be non-toxic and well tolerated by mice up to 250 mg kg(-1) orally and up to 125 mg kg(-1) through parenteral route.


Radiation-induced volatile hydrocarbon production in platelets.
Generation of volatile hydrocarbons (ethane, pentane) as a measure of lipid peroxidation was followed in preparations from platelet-rich plasma irradiated in vitro. The hydrocarbons in the headspace of sealed vials containing irradiated and nonirradiated washed platelets, platelet-rich plasma, or platelet-poor plasma increased with time. The major hydrocarbon, pentane, increased linearly and significantly with increasing log radiation dose, suggesting that reactive oxygen species induced by ionizing radiation result in lipid peroxidation. Measurements of lipid peroxidation products may give an indication of suboptimal quality of stored and/or irradiated platelets.


Paradigm shift in the treatment of tuberous sclerosis: Effectiveness of everolimus.
Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterised by abnormal cell proliferation and differentiation that affects multiple organs and can lead to the growth of hamartomas. Tuberous sclerosis complex is caused by the disinhibition of the protein mTOR (mammalian target of rapamycin). In the past, various therapeutic approaches, even if only symptomatic, have been attempted to improve the clinical effects of this disease. While all of these therapeutic strategies are useful and are still used and indicated, they are symptomatic therapies based on the individual symptoms of the disease and therefore not fully effective in modifying long-term outcomes. A new therapeutic approach is the introduction of allosteric inhibitors of mTORC1, which allow restoration of metabolic homeostasis in mutant cells, potentially eliminating most of the clinical manifestations associated with Tuberous sclerosis complex. Everolimus, a mammalian target of the rapamycin inhibitor, is able to reduce hamartomas, correcting the specific molecular defect that causes Tuberous sclerosis complex. In this review, we report the findings from the literature on the use of everolimus as an effective and safe drug in the treatment of TSC manifestations affecting various organs, from the central nervous system to the heart.


Cloning and characterization of a novel G protein beta-subunit of pearl oyster (Pinctada fucata), and its interaction sites with calmodulin.
A cDNA clone encoding a novel G protein beta subunit of beta1 subclass, pfGbeta1 was isolated from the pearl oyster (Pinctada fucata). The deduced amino acid sequence of pfGbeta1 (341 amino acids) shares high homology to northern European squid (Loligo pealei) and great pond snail (Lymnaea stagnalis) pfGbeta1, while it has diverged from bovine (Bos taurus) and human. The well-conserved amino acid domains in G protein beta subunit, seven WD repeats, were founded in the deduced amino acid sequence. Alignment analysis showed that the beginning amino acid residues in variable fragment of the seventh WD motif are different from any other Gbeta. The prediction of 3D structure of pfGbeta showed that pfGbeta belongs to beta-propeller family proteins whose members contain 4-8 antiparallel beta-sheets resembling the blades of a propeller. In situ hybridization and Northern blotting analysis revealed that the pfGbeta mRNA hybridization signals were widely expressed in various tissues except muscle, with abundantly in epithelia of gill, gonad and outer fold of mantle. We also investigated the interactions between Gbetagamma and calmodulin (CaM), and specific amino acid residues that may be critical for the binding of Gbetagamma to CaM were also identified. Furthermore, the functional studies of the interaction showed that the binding of CaM and Gbetagamma increases the alkaline phosphatase (ALP) activity, an indicator for mineralization in MC3T3-E1 cells. The ALP activity of the mutants of pfGbetagamma that impaired the interactions of Gbetagamma with CaM is higher than the Control group; however, it is lower than the WTC group. Together, these results suggest that the Gbetagamma might interact with CaM and point to the important physiological function in modulating cellular functions.


Concomitant brachiocephalic and coronary artery disease: outcome and decision analysis.
In patients with coronary artery disease, concomitant brachiocephalic disease may affect outcome and influence decision making regarding operative staging, technique, and choice of conduit. Eighty consecutive patients (mean age, 59.3 years; 60.0% male) with concomitant brachiocephalic and coronary artery disease were identified either before (group A, n = 48) or after (group B, n = 32) coronary artery bypass grafting. Patients who had symptomatic brachiocephalic and coronary artery disease before surgery underwent concomitant brachiocephalic reconstruction and coronary artery bypass grafting using either all-vein coronary conduits (n = 41) or vein-and-internal mammary artery conduits (n = 7). Patients who had coronary-subclavian steal syndrome after coronary artery bypass (group B, n = 32) underwent either surgical (n = 5) or endovascular (n = 27) brachiocephalic reconstruction only. All patients were asymptomatic after intervention. Operative mortality was 4.2% for group A and 3.1% for group B. The perioperative stroke rate was 2.1% for group A and 0% for group B. Actuarial 10-year freedom from specific events for group A was as follows: death 59.9 +/- 12.8%, brachiocephalic restenosis 100%, coronary-subclavian steal syndrome 100%, myocardial infarction 83.5 +/- 10.5%, stroke 82.1 +/- 9.9%, redo coronary artery bypass grafting 95.8 +/- 4.1%, other vascular operation 82.2 +/- 8.9%, and adverse cardiac outcome (death, redo coronary artery bypass grafting, or myocardial infarction) 52.9% +/- 13.2% (for patients with all-vein conduits) or 100% (for patients with vein-and-internal mammary artery conduits). At midterm follow-up (mean, 2.92 years), both the surgical and the endovascular treatment subgroups of group B had 100% brachiocephalic patency. Long-term results in a limited population support continued evaluation of concomitant brachiocephalic reconstruction and coronary artery bypass grafting with use of the internal mammary artery conduit in an attempt to improve late survival in patients with concomitant disease. The excellent midterm brachiocephalic patency after either surgical or endovascular treatment of patients with coronary-subclavian steal syndrome supports continued evaluation of both methods.


Antimicrobial and antiproliferative activities of novel synthesized 6-(quinolin-2-ylthio) pyridine derivatives with molecular docking study as multi-targeted JAK2/STAT3 inhibitors.
Quinoline derivatives are attracting considerable interest due to their biological importance. In this paper, several 2-amino-4-aryl-6-(quinolin-2-ylthio)pyridine-3,5-dicarbonitrile derivatives are synthesized by adopting a one-pot reaction of quinoline-2-thione, aromatic aldehydes, and malononitrile in the presence of sodium hydroxide in absolute ethanol. The structures of these newly synthesized compounds were determined using different spectroscopic techniques, including elemental analyses, IR, 1 H NMR, and MS. The synthesized derivatives were screened for their antimicrobial and cytotoxic activities. Compounds 4a, 4b, 4d, and 4e exhibited promising antimicrobial activity compared to antibacterial and antifungal standard drugs. Additionally, 4f, 4d, and 4g showed potent cytotoxic activity against both MCF-7 and A549 cells with IC50 values (6.39-9.3 μM). Our molecular docking results of compound 4f prove good binding affinity toward the three tested proteins as Jak2/STATA3 inhibition and are in accordance with the RT-PCR mRNA expressions of the compound against MCF-7 cells which downregulated the Jak2 and STAT3 genes, and this may be the proposed mode of action for anti-breast cancer activity.


Goal-directed grasping: the dimensional properties of an object influence the nature of the visual information mediating aperture shaping.
An issue of continued debate in the visuomotor control literature surrounds whether a 2D object serves as a representative proxy for a 3D object in understanding the nature of the visual information supporting grasping control. In an effort to reconcile this issue, we examined the extent to which aperture profiles for grasping 2D and 3D objects adheres to, or violates, the psychophysical properties of Weber's law. Specifically, participants grasped differently sized 2D and 3D objects (20, 30, 40, and 50mm of width) and we computed the just-noticeable-difference scores associated with aperture profiles at decile increments of normalized grasping time. The aperture profiles for 2D objects showed an early through late (i.e., 10% through 90%) adherence to Weber's law, whereas the late stages of grasping 3D objects (i.e., >50% of grasping time) produced a fundamental violation of the law's principles. As such, results suggest that grasping a 2D object is a top-down and cognitive task mediated via relative visual information. In contrast, the enriched shape information provided by a 3D object (i.e., stereoscopic vergence and disparity cues) allows for later aperture specification via absolute (Euclidean) visual information. Most notably, our results establish that the dimensional properties of an object influence the visual information mediating motor output, and further indicate that 2D and 3D objects are not representative proxies for one another in understanding the visual control of grasping.


[Laser ablation. Do we still need it?].
Laser ablation (LA) is momentarily the only invasive ablation procedure besides radiofrequency ablation (RFA) which can be performed entirely under magnetic resonance imaging (MRI) guidance. The long-term outcome and morbidity profiles are broadly identical for both modalities, excluding the RFA-specific prevalence for skin burns. The technical and logistic disadvantages of LA have been overcome since the introduction of miniaturized two-component applicators. The main advantage of LA is its superior MRI compatibility. Interference-free imaging during LA allows MR thermometric real-time therapy control without the need for RF filters. High-resolution thermometry in the target zone only makes sense without the extinction artifact of a metal probe and this condition is met only by the glass fibers of LA. An independent therapy monitoring is crucial in modern scenarios of oncologic quality management.


Influence of a polymeric formulation of ketoprofen on its diffusion into cerebrospinal fluid in rats.
Poly(D,L)lactide nanocapsules (NCs) have been proposed as an alternative carrier for many drugs. We investigated the influence of this formulation on the pharmacokinetics of ketoprofen in the plasma and cerebrospinal fluid (CSF). Male Wistar rats were given intraperitoneal dose of ketoprofen (5 mg/kg) in a suspension of NCs or in a carboxymethylcellulose (CMC) solution (reference preparation). Blood and CSF samples were collected at different times up to 24 h after dosing. The unbound fraction of ketoprofen in plasma (f(u)) was determined using ultrafiltration. The total (C(T)) and free (C(F)) concentrations of ketoprofen in plasma and the simultaneous CSF concentrations (C(CSF)) were measured by a HPLC method and the areas under the curve (AUC(T), AUC(F), AUC(CSF)) were calculated. AUC(T) of ketoprofen-loaded NCs in plasma was similar to that of the reference solution, while AUC(F) of the former (5.41 mg/l x h) was higher than that produced by the latter (4.03 mg/l x h). Accordingly, the unbound fraction (f(u)) was higher after administration of NCs than that of the solution (2.5 and 1.8%, respectively). Finally, AUC(CSF) were identical for both formulations. These findings suggest that the binding of ketoprofen to plasma proteins is not the major factor that governs its blood-to-CSF exchanges.


The effects of ablation of visual cortex in neonatal rabbits on the organization of retinothalamic and retinopretectal projections.
Primary visual cortex was ablated unilaterally in neonatal rabbits. Following a survival of 2-4 months, retrograde degeneration of the dorsal lateral geniculate nucleus (LGd) was assessed, and reorganization of retinofugal pathways was studied using methods of anretrograde transport of [3H]proline or of horseradish peroxidase. A complete lesion of primary visual cortex resulted in complete retrograde degeneration of the LGd with no sparing of any class of neurons. The terminations of retinofugal axons in the pretectum and thalamus were compared with those observed in normal animals. No major reorganization of ipsilateral retinofugal projections was observed in either the thalamus and pretectum ipsilateral to the ablated cortex, or in the thalamus and pretectum contralateral to the ablated cortex. However, contralateral retinofugal projections to the thalamus and to the pretectum ipsilateral to the ablated cortex were significantly different from normal. In the thalamus, the projections to the lateral posterior nucleus were expanded in area and increased in density. In the pretectum, the projections to the rostral pretectal areas were greatly increased in area, especially in the region of the olivary pretectal nucleus and posterior pretectal nucleus. However, the density of these projections was not increased relative to normal. Consideration of these results in relation to other published data on the anatomical consequences of neonatal visual cortex lesions, both in mammals which show behavioral sparing following neonatal visual cortex lesions and in mammals which, like the rabbit, show no behavioral sparing, suggests that: (1) behavioral sparing may correlate with patterns of survival or death of neurons in the thalamus and retina; and (2) reorganization of retinofugal pathways is not necessarily associated with behavioral sparing.


Effects of Concentric and Eccentric Strength Training on Fatigue Induced by Concentric and Eccentric Exercises.
To compare the concentric and eccentric training effects on fatigue induced by eccentric and concentric protocols. A total of 22 men and women (22 [3.6] y) were assigned to concentric (GCON, n = 11) or eccentric training (GECC, n = 11). The concentric (CON) and eccentric (ECC) protocols were composed of 4 sets of 20 knee-extension/flexion repetitions. Force losses were analyzed by comparing 10 repetitions' mean torques during the protocols and by verifying the maximal voluntary contraction and rate of torque development before and after the protocols. Muscle damage was assessed using echo intensity of the vastus lateralis 48 h after the protocols. Training consisted of 6 wk of isokinetic exercise at 60°/s (concentric or eccentric) twice weekly. Before training, both protocols resulted in dynamic and isometric force losses in GCON and GECC (P < .01), but the magnitude was greater after the CON protocol than after the ECC protocol (P < .001). After training, both GCON and GECC showed similar force decreases during the CON and ECC protocols (P < .01), and these changes were not different from the pretraining decreases. Regarding maximal voluntary contraction after training, GECC showed lower force decreases than GCON after ECC exercise (-13.7% vs -22.3%, respectively, P < .05), whereas GCON showed lower maximal voluntary contraction decreases after CON exercise compared with pretraining (-29.2%, P < .05). Losses in rate of torque development were similar after the protocols before and after the training regimens. No changes in echo intensity were observed after the protocols before and after training. Both interventions resulted in similar force decreases during fatigue protocols compared with those associated with pretraining.


Rhinogenous optic neuritis with full recovery of vision - The role of endoscopic optic nerve decompression and a review of literature.
Optic neuritis resulting from paranasal sinusitis is an infrequently described but clinically important and treatable entity. The role of optic nerve decompression has been well established in atraumatic optic neuropathies which are compressive in origin. However, its role in optic neuritis and other infective or inflammatory processes is lacking, and the role for early surgical intervention remains controversial. In this case report, we describe a patient who presented with sudden onset of right vision loss secondary to optic neuritis from pansinusitis. He was treated with systemic antibiotics and steroids along with an urgent endoscopic sinus surgery with optic nerve decompression. Full restoration of his vision was recorded within 24 h of surgical decompression. Optic neuritis secondary to paranasal sinusitis is a clinically important entity and timely diagnosis and decompression is key to vision restoration.


Diagnostic Value of the Second Lumbrical-Interosseous Distal Motor Latency Comparison Test in Severe Carpal Tunnel Syndrome.
To examine the usefulness of the second lumbrical-interosseous (2L-INT) distal motor latency (DML) comparison test in localizing median neuropathy to the wrist in patients with absent median sensory and motor response in routine nerve conduction studies. Electrodiagnostic results from 1,705 hands of patients with carpal tunnel syndrome (CTS) symptoms were reviewed retrospectively. All subjects were evaluated using routine nerve conduction studies: median sensory conduction recorded from digits 1 to 4, motor conduction from the abductor pollicis brevis muscle, and the 2L-INT DML comparison test. Four hundred and one hands from a total of 1,705 were classified as having severe CTS. Among the severe CTS group, 56 hands (14.0%) showed absent median sensory and motor response in a routine nerve conduction study, and, of those hands, 42 (75.0%) showed an abnormal 2L-INT response. The 2L-INT DML comparison test proved to be a valuable electrodiagnostic technique in localizing median mononeuropathy at the wrist, even in the most severe CTS patients.


Control of graft-versus-host disease with rabbit anti-thymocyte globulin, rituximab, and bortezomib in TCRαβ/CD19-depleted graft transplantation for leukemia in children: a single-center retrospective analysis of two GVHD-prophylaxis regimens.
Both acute GVHD and chronic GVHD remain the leading cause of morbidity and death after allogeneic HSCT. We conducted a retrospective analysis comparing two GVHD-prophylaxis regimens: 35 patients received "Regimen 1" (horse ATG, tacrolimus, and methotrexate) and 46 "Regimen 2" (rabbit ATG, rituximab, and peritransplant bortezomib). All 81 patients with a median age of 9 (0.6-23) years with ALL (n = 31) or AML (n = 50) in complete remission received TCRαβ/CD19-depleted transplants between May 2012 and October 2016, from 40 HLA-matched unrelated and 41 haploidentical donors. After a median follow-up of 3.9 years, the CI of acute GVHD II-IV was 15% (95% CI: 7-30) in the "Regimen 2" group and 34% (95% CI: -54) in the "Regimen 1" group, P = .05. "Regimen 2" was also more effective in the prevention of chronic GVHD; the CI at 1 year after HSCT was 7% (95% CI: 2-19) vs 31% (95% CI: 19-51), P = .005. The CI of relapse at 3 years adjusted for the GVHD-prophylaxis regimen groups 31% (95% CI: 19-51) for the "Regimen 1" vs 21% (95% CI: 11-37) for the "Regimen 2", P = .3. The retrospective observation suggests that the use of the rATG, rituximab, and bortezomib was associated with significantly lower rate of GVHD without the loss of anti-leukemic activity.


Maternal rehospitalization after singleton term vaginal delivery.
To determine risk factors for maternal rehospitalization after term vaginal delivery. The study group consisted of all women who were rehospitalized following singleton vaginal deliveries during 1996-1998 (n = 194). The control group consisted of 427 women who were not rehospitalized during the same period. The incidence of rehospitalization was 0.75% (194/25885). Maternal chronic diseases, preterm contractions and pre-eclampsia rates were significantly higher among the study group as compared to the controls (25.3% vs. 8.4%, p < 0.001; 6.7% vs. 2.8%, p = 0.022; 9.3% vs. 4.9%, p = 0.037, respectively). Duration of labor was significantly longer in the study group as opposed to the controls (379 +/- 406 min vs. 259 +/- 276 min, p < 0.001). The rates of postpartum hemorrhage, blood transfusion and antibiotic treatment during delivery hospitalization were significantly higher among the study group (1.5% vs. 0.2%, p = 0.021; 4.6% vs. 0.7%, p < 0.001; 26.8% vs. 14.1%, p < 0.001, respectively). Using a forward logistic regression analysis, prolonged labor and blood transfusion during labor were found as independent risk factors associated with rehospitalization (OR 1.001, 95% CI 1.001-1.002, p = 0.001; OR 4.751, 95% CI 1.698-13.292, p = 0.003). In contrast, vertex presentation had a protective effect against rehospitalization (p = 0.027, OR 0.084, 95% CI 0.009-0.758). Blood transfusion and prolonged labor are independent risk factors for rehospitalization after term vaginal delivery. Special attention should be given during the early postpartum period to patients receiving blood transfusions and those with prolonged deliveries, in order to reduce rehospitalization rates.


[Rational use of modern substances for the treatment of HIV-infection].
Treatment options for HIV-infection have been improved significantly. Drugs with new modes of action have been licensed (integrase inhibitor and CCR5-inhibitor) as well as drugs within the existing classes, but improved activity in case of resistance (e.g. darunavir, tipranavir, etravirin). The treatment goal today is complete and durable suppression of viral replication in treatment-naïve as well as pre-treated patients. The significance of new drugs in the clinical setting will be defined more precisely in the near future, as all new substances have been licensed for pre-treated patients only so far.


Evaluation of the antigenic variation within type-A foot and mouth disease virus isolates from Asia.
The serological interrelationships among 17 type A FMD virus strains from eight Asian countries were studied by the two-dimensional microneutralization test. Complex direct and indirect relationships were observed. Overall, however, the virus strains studied could be classified as belonging to the A22 group on the basis of r value differentiation at P less than 0.01.


Improved Prediction Model of Protein and Peptide Toxicity by Integrating Channel Attention into a Convolutional Neural Network and Gated Recurrent Units.
In recent times, the importance of peptides in the biomedical domain has received increasing concern in terms of their effect on multiple disease treatments. However, before successful large-scale implementation in the industry, accurate identification of peptide toxicity is a vital prerequisite. The existing computational methods have reached good results from toxicity prediction, and we present an improved model based on different deep learning architectures. The modification mainly focuses on two aspects: sequence encoding and variational information bottlenecks. Consequently, one of our modified plans shows an obvious increase in sensitivity, while the rest show good performance meanwhile adding novelty in the peptide toxicity prediction domain. In detail, our best model could achieve an accuracy of 97.38 and 95.03% in protein and peptide toxicity predictions, respectively. The performance was superior to previous predictors on the same datasets.


The PTW microSilicon diode: Performance in small 6 and 15 MV photon fields and utility of density compensation.
We have experimentally and computationally characterized the PTW microSilicon 60023-type diode's performance in 6 and 15 MV photon fields ≥5 × 5 mm2 projected to isocenter. We tested the detector on- and off-axis at 5 and 15 cm depths in water, and investigated whether its response could be improved by including within it a thin airgap. Experimentally, detector readings were taken in fields generated by a Varian TrueBeam linac and compared with doses-to-water measured using Gafchromic film and ionization chambers. An unmodified 60023-type diode was tested along with detectors modified to include 0.6, 0.8, and 1.0 mm thick airgaps. Computationally, doses absorbed by water and detectors' sensitive volumes were calculated using the EGSnrc/BEAMnrc Monte Carlo radiation transport code. Detector response was characterized using k Q c l i n , 4 cm f c l i n , 4 cm , a factor that corrects for differences in the ratio of dose-to-water to detector reading between small fields and the reference condition, in this study 5 cm deep on-axis in a 4 × 4 cm2 field. The greatest errors in measurements of small field doses made using uncorrected readings from the unmodified 60023-type detector were over-responses of 2.6% ± 0.5% and 5.3% ± 2.0% determined computationally and experimentally, relative to the reading-per-dose in the reference field. Corresponding largest errors for the earlier 60017-type detector were 11.9% ± 0.6% and 11.7% ± 1.4% over-responses. Adding even the thinnest, 0.6 mm, airgap to the 60023-type detector over-corrected it, leading to under-responses of up to 4.8% ± 0.6% and 5.0% ± 1.8% determined computationally and experimentally. Further, Monte Carlo calculations indicate that a detector with a 0.3 mm airgap would read correctly to within 1.3% on-axis. The ratio of doses at 15 and 5 cm depths in water in a 6 MV 4 × 4 cm2 field was measured more accurately using the unmodified 60023-type detector than using the 60017-type detector, and was within 0.3% of the ratio measured using an ion chamber. The 60023-type diode's sensitivity also varied negligibly as dose-rate was reduced from 13 to 4 Gy min-1 by decreasing the linac pulse repetition frequency, whereas the sensitivity of the 60017-type detector fell by 1.5%. The 60023-type detector performed well in small fields across a wide range of beam energies, field sizes, depths, and off-axis positions. Its response can potentially be further improved by adding a thin, 0.3 mm, airgap.


Stress breaks universal aging behavior in a metallic glass.
Numerous disordered materials display a monotonous slowing down in their internal dynamics with age. In the case of metallic glasses, this general behavior across different temperatures and alloys has been used to establish an empirical universal superposition principle of time, waiting time, and temperature. Here we demonstrate that the application of a mechanical stress within the elastic regime breaks this universality. Using in-situ x-ray photon correlation spectroscopy (XPCS) experiments, we show that strong fluctuations between slow and fast structural dynamics exist, and that these generally exhibit larger relaxation times than in the unstressed case. On average, relaxation times increase with stress magnitude, and even preloading times of several days do not exhaust the structural dynamics under load. A model Lennard-Jones glass under shear deformation replicates many of the features revealed with XPCS, indicating that local and heterogeneous microplastic events can cause the strongly non-monotonous spectrum of relaxation times.


Toward Minimum Standards for Certifying Patient Decision Aids: A Modified Delphi Consensus Process.
The IPDAS Collaboration has developed a checklist and an instrument (IPDASi v3.0) to assess the quality of patient decision aids (PDAs) in terms of their development process and shared decision-making design components. Certification of PDAs is of growing interest in the US and elsewhere. We report a modified Delphi consensus process to agree on IPDASi (v3.0) items that should be considered as minimum standards for PDA certification, for inclusion in the refined IPDASi (v4.0). A 2-stage Delphi voting process considered the inclusion of IPDASi (v3.0) items as minimum standards. Item scores and qualitative comments were analyzed, followed by expert group discussion. One hundred and one people voted in round 1; 87 in round 2. Forty-seven items were reduced to 44 items across 3 new categories: 1) qualifying criteria, which are required in order for an intervention to be considered a decision aid (6 items); 2) certification criteria, without which a decision aid is judged to have a high risk of harmful bias (10 items); and 3) quality criteria, believed to strengthen a decision aid but whose omission does not present a high risk of harmful bias (28 items). This study provides preliminary certification criteria for PDAs. Scoring and rating processes need to be tested and finalized. However, the process of appraising the quality of the clinical evidence reported by the PDA should be used to complement these criteria; the proposed standards are designed to rate the quality of the development process and shared decision-making design elements, not the quality of the PDA's clinical content.


Dejerine-Sottas syndrome associated with point mutation in the peripheral myelin protein 22 (PMP22) gene.
Dejerine-Sottas syndrome is a hypertrophic, demyelinating neuropathy which appears to demonstrate autosomal recessive inheritance in most pedigrees. Clinical symptoms are similar but more severe than Charcot-Marie-Tooth disease type 1 (CMT1), of which the major subtype, CMT1A, results either from duplication of a 1.5-megabase DNA region in chromosome 17p11.2-p12 containing the myelin gene PMP22, or from PMP22 point mutation. Mutational analysis of the PMP22 coding region in two unrelated Dejerine-Sottas patients identified individual missense point mutations present in the heterozygous state. These findings suggest that Dejerine-Sottas syndrome can result from dominant point mutation alleles of PMP22.


Atrial fibrillation following autologous stem cell transplantation in patients with multiple myeloma: incidence and risk factors.
Atrial fibrillation (AF) often develops in patients with multiple myeloma following autologous stem cell transplantation (ASCT), but the exact incidence of, and the risk factors for AF have not been described. In this study, we sought to determine the incidence of AF in patients with multiple myeloma undergoing ASCT. Patients who received ASCT for multiple myeloma between January 2000 and December 2009 were identified using the ICD-9 codes for multiple myeloma and ASCT, and formed the basis of this report. The study included 278 patients (mean age, 63 ± 9.5 years). A total of 75 (27%) patients developed AF at a mean duration of 14.8 days following ASCT. On multiple regression analysis, baseline renal dysfunction (odds ratio 15.2 [confidence interval 5.08-45.6]), left ventricular systolic dysfunction (9.55 [2.78-32.79]), dilated left atrium on echocardiogram (4.97 [1.8-13.78]), and hypertension (3.6 [1.36-9.52]) were significantly associated with the development of AF after ASCT. The presence of light-chain secretion (0.21 [0.07-0.6]) was associated with a lower incidence of AF. Age, gender, and race were not significantly associated with the development of AF after ASCT. AF is very frequent in patients with multiple myeloma when they receive ASCT. The presence of abnormal renal function, left ventricular systolic dysfunction, dilated left atrium, or hypertension at baseline identifies patients at high risk of developing AF following ASCT.


Epithelial-mesenchymal transition and mesenchymal-epithelial transition are essential for the acquisition of stem cell properties in hTERT-immortalised oral epithelial cells.
Evidence has shown that mesenchymal-epithelial transition (MET) and epithelial-mesenchymal transition (EMT) are linked to stem cell properties. We currently lack a model showing how the occurrence of MET and EMT in immortalised cells influences the maintenance of stem cell properties. Thus, we established a project aiming to investigate the roles of EMT and MET in the acquisition of stem cell properties in immortalised oral epithelial cells. In this study, a retroviral transfection vector (pLXSN-hTERT) was used to immortalise oral epithelial cells by insertion of the hTERT gene (hTERT(+)-oral mucosal epithelial cell line [OME]). The protein and RNA expression of EMT transcriptional factors (Snail, Slug and Twist), their downstream markers (E-cadherin and N-cadherin) and embryonic stem cell markers (OCT4, Nanog and Sox2) were studied by reverse transcription PCR and Western blots in these cells. Some EMT markers were detected at both mRNA and protein levels. Adipocytes and bone cells were noted in the multi-differentiation assay, showing that the immortal cells underwent EMT. The differentiation assay for hTERT(+)-OME cells revealed the recovery of epithelial phenotypes, implicating the presence of MET. The stem cell properties were confirmed by the detection of appropriate markers. Altered expression of α-tubulin and γ-tubulin in both two-dimensional-cultured (without serum) and three-dimensional-cultured hTERT(+)-OME spheroids indicated the re-programming of cytoskeleton proteins which is attributed to MET processes in hTERT(+)-OME cells. EMT and MET are essential for hTERT-immortalised cells to maintain their epithelial stem cell properties.


Regio- and stereocontrolled Diels-Alder reaction tethered by Asp-Thr dipeptide.
The Asp-Thr tethered Diels-Alder reaction of 1a was accomplished to provide 2a exclusively in a regio- and stereoselective manner.


Identification of key genes and regulators associated with carotenoid metabolism in apricot (Prunus armeniaca) fruit using weighted gene coexpression network analysis.
Carotenoids are a class of terpenoid pigments that contribute to the color and nutritional value of many fruits. Their biosynthetic pathways have been well established in a number of plant species; however, many details of the regulatory mechanism controlling carotenoid metabolism remain to be elucidated. Apricot is one of the most carotenoid-rich fruits, making it a valuable system for investigating carotenoid metabolism. The purpose of this study was to identify key genes and regulators associated with carotenoid metabolism in apricot fruit based on transcriptome sequencing. During fruit ripening in the apricot cultivar 'Luntaixiaobaixing' (LT), the total carotenoid content of the fruit decreased significantly, as did the levels of the carotenoids β-carotene, lutein and violaxanthin (p < 0.01). RNA sequencing (RNA-Seq) analysis of the fruit resulted in the identification of 44,754 unigenes and 6916 differentially expressed genes (DEGs) during ripening. Among these genes, 33,498 unigenes were annotated using public protein databases. Weighted gene coexpression network analysis (WGCNA) showed that two of the 13 identified modules ('blue' and 'turquoise') were highly correlated with carotenoid metabolism, and 33 structural genes from the carotenoid biosynthetic pathway were identified. Network visualization revealed 35 intramodular hub genes that putatively control carotenoid metabolism. The expression levels of these candidate genes were determined by quantitative real-time PCR analysis, which showed ripening-associated carotenoid accumulation. This analysis revealed that a range of genes (NCED1, CCD1/4, PIF3/4, HY5, ERF003/5/12, RAP2-12, AP2, AP2-like, BZR1, MADS14, NAC2/25, MYB1R1/44, GLK1/2 and WRKY6/31/69) potentially affect apricot carotenoid metabolism during ripening. Based on deciphering the molecular mechanism involved in ripening, a network model of carotenoid metabolism in apricot fruit was proposed. Overall, our work provides new insights into the carotenoid metabolism of apricot and other species, which will facilitate future apricot functional studies and quality breeding through molecular design.


Economic implications of bovine leukemia virus infection in mid-Atlantic dairy herds.
To determine the baseline costs of bovine leukemia virus (BLV) infection, including costs of clinical disease and subclinical infection, in a dairy herd representative of the mid-Atlantic region and compare these costs with the cost of a test-and-manage BLV control program. Stochastic spreadsheet model. A commercial Holstein dairy herd with 100 milking cows. A spreadsheet model was developed. The overall cost of infection included the cost of clinical disease (ie, lymphosarcoma [LS]) and the effects of subclinical infection on milk production and premature culling. Model input values and distributions were designed to reflect economic conditions in the mid-Atlantic region. Relative costs of infection and control were calculated for infection prevalences of 20, 50, and 80%. Estimated mean cost to the producer per case of LS was 412 dollars; for a herd with a 50% prevalence of BLV infection, annual incidence of LS was 0.66. Mean annual cost of subclinical infection at a 50% prevalence of infection was 6,406 dollars. Mean annual cost of a test-and-manage control program was 1,765 dollars. The cost of clinical disease and subclinical infection varied substantially with the prevalence of infection, whereas the cost of control varied with herd size. Results suggested that a basic BLV control program may be economically beneficial in herds in which the prevalence of BLV infection is > or = 12.5%. Farm-specific considerations may factor prominently when weighing the costs and benefits of an individual BLV control program.


On handling the layered structure of the skull in transcranial direct current stimulation models.
In a tDCS model study, the accuracy of isotropic and anisotropic single-layer approximations to the actual three-layered skull is evaluated. For both approximation models, the average difference in brain current density with respect to the layered skull model are shown to be small. We conclude that both approximations can be used to accurately compute the current density in the brain, provided that the radial conductivity in the model matches the effective radial conductivity of the three-layered skull.


Contemporary Systematic Review of Health-Related Quality of Life Outcomes in Locoregional Therapies for Hepatocellular Carcinoma.
Health-related quality of life has become an important aspect in oncologic decision making. Recent data suggest that Health-Related Quality of Life (HRQoL) measurements can play an important prognostic role in patients with hepatocellular carcinoma (HCC). Locoregional therapies (LRTs) such as radiofrequency ablation, transarterial chemoembolization, and radioembolization (TARE) are important parts of HCC management. Results demonstrated that radiofrequency ablation treatment results in improving HRQoL compared to surgery for up to 3 years after treatment. Between TARE and transarterial chemoembolization, TARE provides the most benefit in terms of HRQoL. This systematic review investigated contemporary data surrounding HRQoL in patients undergoing LRTs and its impact on clinical decision making.


Laparoscopic splenectomy in the elderly: a morbid procedure?
Laparoscopic splenectomy has emerged as the gold standard for elective splenectomy. Few reports have critically evaluated the results of laparoscopic splenectomy in elderly patients. All laparoscopic splenectomies performed between August 19, 1998 and June 8, 2004 were reviewed retrospectively. Of 235 splenectomies, 188 were performed for patients younger than age 65 years (group 1), and 45 were performed for patients 65 years of age or older (group 2). The groups were demographically similar, except for the average age and the American Society of Anesthesiology (ASA) classification. Operative characteristics were similar, but the average length of hospital stay differed: 2.2 days for group 1 and 3.9 days for group 2 (p < 0.03). Complications occurred for 8.5% of group 1 and 17.8% of group 2, but the percentages were similar by ASA class. Elderly patients have a higher rate of complications after laparoscopic splenectomy. The complications are similar when matched for ASA class, but a larger percentage of elderly patients fall into higher ASA class ratings.


Checking in on check-out: Survey of Learning Priorities in Primary Care Residency Teaching Clinics.
Despite focus on increasing the quality of ambulatory education training, few studies have examined residents' perceptions of learning during case discussions with their preceptors (i.e., "check-out"). The objective of this study was to assess the difference between residents' and preceptors' perceptions of behaviors that should occur during check-out discussions. We conducted a cross-sectional survey of categorical internal medicine and family medicine residents and preceptors. The survey was distributed electronically and assessed 20 components of the check-out discussion. Of 38 preceptors, 22 (61%) completed the survey. Of 172 residents, 82 (48%) completed the survey. For residents, we identified discrepancies in desired and perceived check-out behaviors. Specifically, utilizing a dependent sample t-test, residents felt that all 20 areas needed additional teaching during check-out (P < 0.05). Preceptors believed that demonstrating physical examination skills in the patient room during check-out was significantly more important than did residents (P = 0.01). Increasing years of preceptor experience did not statistically relate to their valuation of components important to residents. Our research highlighted a major deficiency in training in the check-out process, with residents desiring more patient management education in all components. Moreover, faculty and residents do not necessarily agree with what is an important focus in the "teachable moment." Our results serve as a training needs assessment for future faculty development seminars and highlight the need to consider resident learning needs in general.


Willingness to be tested for a secondary cause of hypertension: a survey of the Australian general community.
Primary aldosteronism (PA) represents the most common and potentially curable cause of secondary hypertension. However, PA is not commonly screened for, and up to 34% of patients who screen positive do not complete the full diagnostic process. This suggests that the diagnostic process may pose a barrier to patients and may contribute to the under-diagnosis of PA. To evaluate the willingness of the Australian general public to undergo testing for secondary causes of hypertension and identify enablers or barriers to testing from the patients' perspective. An online survey containing questions on knowledge and attitudes towards hypertension, willingness to be tested and enablers/barriers towards testing was distributed to the Australian community. Of 520 adult respondents (mean age 50.4 years, SD 27.3 years; 28.8% hypertensive; 56.0% female), the majority of non-hypertensive and hypertensive respondents (82.7% vs 70.0%; P = 0.03) were willing to undergo testing for a secondary cause of hypertension that involved blood and urine tests. Greater knowledge of hypertensive risk modification strategies and complications was predictive of willingness to be tested, whereas age, sex, education level, geographic location, socio-economic status and cardiovascular comorbidities were not. The top three barriers to testing included fear of a serious underlying condition, lack of belief in further testing and increased stress associated with further testing. A high proportion of patients are willing to engage in testing for a secondary cause of hypertension. Education about the risks associated with hypertension and the testing process may overcome several barriers to testing.


Systematic review of cross-cultural adaptations of hip-specific patient-reported outcome measures in Spanish.
The aim of this study was to conduct a systematic review of the quality of the transcultural adaptation procedure and the clinimetric properties of the self-administered hip-disability functional assessment questionnaires adapted for the Spanish population. We searched the MEDLINE, EMBASE, CINAHL and Web of Science databases (from inception until June 2016) to locate all the scales adapted to Spanish and to analyze the different phases of the adaptation process and its psychometric properties. Eight scales were identified, and were grouped into three sections, according to the type of diseases in which they can be used: a) lower limb: Lower Limb Functional Index (LLFI), Lower Extremity Functional Scale (LEFS) and Arthrosis of Membres Inférieurs et Qualité de vie (AMICAL); b) knee and/or hip: Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, Osteoarthritis Knee and Hip Quality of Life (OAKHQOL) and Hip and Knee Questionnaire (HKQ); and c) specific for hip: Hip Outcome Score (HOS) and International Hip Outcome Tool-33 (iHOT-33). The transcultural adaptation procedure was satisfactory in all cases, albeit somewhat less rigorous for the HKQ and LLFI than for the remaining questionnaires. No study evaluated all the psychometric properties. We currently have 8 hip-disability functional assessment questionnaires adapted to Spanish with satisfactory psychometric properties. We can measure the patient's perceived impact of his or her hip disease by selecting, among the different options, those alternatives that best fit our clinical or research objectives.


TiO2 nanorod/nanotube interface reconstruction and synergistic role of oxygen vacancies and gold in H-Au-TiO2 NR/NT for photoelectrochemical bacterial inactivation and water splitting.
Photoelectrochemical (PEC) water splitting by semiconductor photoanodes is limited by sluggish water oxidation kinetics coupled with serious charge recombinations. In this paper, an effective strategy of TiO2 nanorod/nanotube nanostructured interface reconstruction, oxygen vacancies and surface modification were employed for stability and efficient charge transport in the photoanodes. Successive anodization and hydrothermal routes were adopted for the TiO2 NR/NT photoanodes interface reconstruction, followed by Au nanoparticles/clusters (Au NP) loading and hydrogen treatment. This resulted in H-Au-TiO2 NR/NT photoanodes. A three-dimensional structure of TiO2 NR on TiO2 NT/Ti foil nanotubes achieved the highest photocurrent density (1.42 mA cm-2 at 0.3 V vs. Ag/AgCl). The optimal oxygen vacancies and Au NP loading on TiO2 NR/NT exhibited 1.62 mA cm-2 photocurrent density at 0.3 V vs. Ag/AgCl in H-Au-TiO2 NR/NT photoelectrode, which is eight times higher than the TiO2 NT/Ti foil. TRPL analyses confirm the hydrogen treatments to TiO2 exhibited the emission lifetime (46 ns) in the H-Au-TiO2 NR/NT photoanodes due to newly formed lower Ti3+-related trapped electron states and Au NP. The optimum H-Au (4)-TiO2 NR/NT photoanodes achieved 95% photoelectrochemical (PEC) bacterial inactivation and effective PEC water splitting with (278 and 135.4) μmol of hydrogen and oxygen generation, respectively. In this study, oxygen vacancies combined with gold particles and interface reconstruction provide an innovative way to design effective photoelectrodes.


Cohort study of 1241 patients to identify predictors of negative appendicectomy.
Acute Appendicitis is the most common surgical presentation within Australia. Despite the increasing use of radiological investigations to aid clinical diagnosis, many appendectomies result in a histologically normal appendix. This study examines the histological negative appendicectomy rate (NAR) in a metropolitan hospital and determine factors associated with a negative appendicectomy (NA). Patients who underwent emergency appendicectomy for suspected acute appendicitis at Logan Hospital, Australia, between February 2016 and March 2019 inclusive were included. Clinicopathologic and imaging variables were analysed for associations with NA. A total of 1241 patients underwent emergency appendicectomy of which 121 patients (9.8%) had a NA. The NAR for clinical diagnosis alone (no imaging) was 9.9%, 14.5% for ultrasonography alone and computed tomography scan alone was 4.9%. Univariate analysis revealed age <27 years (P < 0.001), absence of hypertension (P = 0.008), symptoms >48 hours (P < 0.001), absence of leucocytosis (P < 0.001), undergoing ultrasonography only (P < 0.001), undergoing computed tomography scan only (P < 0.001), macroscopically normal appendix (P < 0.001) and time to operation >24 hours (P < 0.001) were associated with NA. Multivariate analysis identified symptoms >48 h at presentation (odds ratio (OR) 1.98, 95% confidence interval (CI) 1.20-3.24; P = 0.007), absence of leucocytosis (OR 2.41, 95% CI 1.52-3.81; P < 0.001) and macroscopically normal appendix (OR 5.70, 95% CI 3.49-9.33; P < 0.001) to be associated with a NA. The NAR reported is lowest in an Australian institution. The identified predictors of NA will be useful in identifying patients who would truly benefit from an appendicectomy versus those would have a higher rate of NA who may be suitable to be treated non-operatively to be spared the unnecessary morbidity of surgery.


Ultrasonic particle volume fraction profiling: an evaluation of empirical approaches.
We discuss empirical techniques to extract quantitative particle volume fraction profiles in particle-laden flows using an ultrasound transducer. A key step involves probing several uniform suspensions with varying bulk volume fractions from which two key volume fraction dependent calibration parameters are identified: the peak backscatter amplitude (acoustic energy backscattered by the initial layer of the suspension) and the amplitude attenuation rate (rate at which the acoustic energy decays with depth owing to scattering losses). These properties can then be used to reconstruct spatially varying particle volume fraction profiles. Such an empirical approach allows circumventing detailed theoretical models which characterize the interaction between ultrasound and suspensions, which are not universally applicable. We assess the reconstruction techniques via synthetic volume fraction profiles and a known particle-laden suspension immobilized in a gel. While qualitative trends can be easily picked up, the following factors compromise the quantitative accuracy: (1) initial reconstruction errors made in the near-wall regions can propagate and grow along the reconstruction direction, (2) multiple scattering can create artefacts which may affect the reconstruction, and (3) the accuracy of the reconstruction is very sensitive to the goodness of the calibration. Despite these issues, application of the technique to particle-laden pipe flows shows the presence of a core with reduced particle volume fractions in laminar flows, whose prominence reduces as the flow becomes turbulent. This observation is associated with inertia-induced radial migration of particles away from the pipe axis and is observed in flows with bulk volume fractions as high as 0.08. Even transitional flows with low levels of intermittency are not devoid of this depleted core. In conclusion, ultrasonic particle volume fraction profiling can play a key complementary role to ultrasound-based velocimetry in studying the internal features of particle-laden flows.


Relationships between extraction and metabolism of glucose, blood flow, and tissue blood volume in regions of rat brain.
Studies were made on the relationships between the rate of glucose metabolism, the transport of glucose between plasma and brain, cerebral blood flow, and blood content. Conscious control rats were compared with rats with intense tremors induced with cismethrin. The influence of plasma glucose concentration was studied by fasting some animals overnight prior to the induction of tremors. Mean plasma glucose was 8.83 mM in controls, 12.57 mM in fed rats with tremors, and 4.94 mM in rats fasted overnight prior to induction of tremors. Of 12 brain regions studied, nine showed an increased rate of glucose utilization in both fed and fasted trembling rats. Cerebellum had the highest percentage increase (200%). Rates of unidirectional glucose influx in fed trembling rats were significantly greater than those in controls in eight regions. In fasted animals, rates were the same as in controls, except in cerebellum, where it was 1.6 times higher. These high rates of glucose influx at low plasma glucose concentrations were indicative of a change in kinetic parameters of glucose transport. Unidirectional glucose influx rates were transformed to estimates of maximal transport rates (Tmax), based on the Michaelis-Menten equation. Average plasma glucose concentrations in regional capillaries (c) were calculated and shown to be maintained at values close to arterial plasma glucose concentrations (Ca), in all brain regions of each group. In trembling rats, Tmax for each brain region was higher than that in controls. In fasted rats with tremors, Tmax was higher in several brain regions than in fed rats. Tmax in cerebellum was 3.37, 4.71, and 7.89 mumol g-1 min-1 in control, fed trembling, and fasted trembling rats, respectively. Blood flow increased significantly in all regions in rats with tremors and was higher in fasted than in fed animals. There was only a weak correlation between blood flow and Tmax. Blood content of several regions increased in rats with tremors, and there was a strong correlation between Tmax and tissue blood volume. Results are consistent with localized regulatory links between blood flow, capillary surface area, and glucose transport in response to metabolic demand and hypoglycaemia. These involve changes in the linear velocity of blood through capillaries and in the extent of capillary recruitment.


Lasers and Intense Pulsed Light Hidradenitis Suppurativa.
Lasers and intense pulsed light (IPL) treatment are useful for the treatment of hidradenitis suppurativa (HS). Carbon dioxide lasers are used for cutting or vaporization of the affected area. It is a effective therapy for the management of severe and recalcitrant HS with persistent sinus tract and scarring, and can be performed under local anesthesia. HS has a follicular pathogenesis. Lasers and IPL targeting the hair have been found useful in treating HS by reducing the numbers of hairs in areas with HS. The methods have few side effects, but the studies are preliminary and need to be repeated.


A new scoring system for gallbladder cancer (aiding treatment algorithm): an analysis of 335 patients.
There is currently no preoperative staging/scoring system available for gallbladder cancer. Unfortunately, in gallbladder cancer, patients manifest advanced stages of the disease. There is need for a methodology that can aid accurate preoperative staging and the subsequent treatment algorithm. We thus sought to validate a new scoring system, the Tata Memorial Hospital Staging System (TMHSS), for gallbladder cancer. TMHSS is based on the cumulative impact of specific features of computed tomographic scan, presence or absence of jaundice, and serum cancer antigen 19-9 levels. This scoring system was first proposed in 2004. Patients with gallbladder cancer were enrolled onto the testing sample for TMHSS to ascertain its validity. A total of 335 consecutive patients with gallbladder cancer who sought care at the Tata Memorial Hospital between May 1, 2005, and December 31, 2006, were studied. Treatment was suggested on the basis of current existing protocols. Each patient was assigned a TMHSS score, and the treatment decision taken was compared with the algorithm generated for each individual score. Concurrence of the decision taken with the score generated algorithm was tested by the Kendall tau-b test. Ordinal-by-ordinal analysis of the value of the test was .75, which showed excellent concurrence and a statistically significant P value (P < .0001). TMHSS provides an excellent correlative treatment plan for patients with gallbladder cancer. It has the potential to reduce unnecessary surgical explorations and to direct patients to the ideal treatment strategy, thereby offering a degree of prognostication.


Prevalence and risk factors for epiretinal membranes in a Japanese population: the Hisayama study.
To examine the prevalence and risk factors for epiretinal membranes (ERMs) in a sample Japanese population. In 1998 a cross-sectional community survey was conducted among residents of Hisayama. A total of 688 men and 1087 women living in Hisayama, Japan, aged 40 years or older consented to participate in the study. Each participant underwent a comprehensive physical examination that included an ophthalmic examination. The presence of ERMs was judged from grading based on fundus examination using indirect ophthalmoscopy, slit lamp examination, and color fundus photographs. This study used non-stereoscopic 45 degrees fundus photographs to grade ERMs, whereas the other population-based studies used 30 degrees stereoscopic fundus photographs, which might explain some differences in prevalence of ERMs. Multiple logistic regression analysis was performed on the cross-sectional data to determine the risk factors for ERMs. The following ten possible risk factors were used: age; gender; hypertension; diabetes; serum cholesterol; serum HDL cholesterol; serum triglycerides; smoking habits; alcohol intake; and body mass index. The prevalence of ERMs was 4.0%, and increased with age. The ERMs were more prevalent in women (4.3%) than in men (3.5%). Multiple logistic regression analysis showed that age and serum cholesterol significantly associated with ERMs. This study suggests that ERMs are less common in the Japanese population than in similar populations in Western countries, and that hypercholesterolemia is a relevant risk factor for ERMs.


Limited evidence for evolutionarily conserved targeting of long non-coding RNAs by microRNAs.
Long non-coding RNAs (lncRNAs) are emerging as important regulators of cell physiology, but it is yet unknown to what extent lncRNAs have evolved to be targeted by microRNAs. Comparative genomics has previously revealed widespread evolutionarily conserved microRNA targeting of protein-coding mRNAs, and here we applied a similar approach to lncRNAs. We used a map of putative microRNA target sites in lncRNAs where site conservation was evaluated based on 46 vertebrate species. We compared observed target site frequencies to those obtained with a random model, at variable prediction stringencies. While conserved sites were not present above random expectation in intergenic lncRNAs overall, we observed a marginal over-representation of highly conserved 8-mer sites in a small subset of cytoplasmic lncRNAs (12 sites in 8 lncRNAs at 56% false discovery rate, P = 0.10). Evolutionary conservation in lncRNAs is generally low but patch-wise high, and these patches could, in principle, harbor conserved target sites. However, while our analysis efficiently detected conserved targeting of mRNAs, it provided only limited and marginally significant support for conserved microRNA-lncRNA interactions. We conclude that conserved microRNA-lncRNA interactions could not be reliably detected with our methodology.


Pancreatic polypeptide: a possible role in the regulation of food intake in the mouse. Hypothesis.
Pancreatic polypeptide (PP) is a recently identified hormone produced by pancreatic endocrine cells. The islets of genetically obese mice (ob/ob, C57 BL/6J), which are suspected to lack a circulating satiety factor, contain relatively few of the PP-producing cells. Administration of bovine pancreatic polypeptide (bPP) reduces food intake and suppresses body weight gain in the hyperphagic obese mice. It is postulated that PP participates in the regulation of food intake in a manner as yet undefined.


Low-level exposure to air pollution and risk of adverse birth outcomes in Hillsborough County, Florida.
In this retrospective cohort (1998 to 2007), 145,445 singleton live births in Hillsborough, Florida, were analyzed to elucidate the relationship between fetal morbidity and prenatal exposure to six criteria air pollutants. This study was based on three linked databases: Florida Hospital Discharge, vital statistics records, and air pollution meteorological data from the Environmental Protection Agency. The primary outcomes of interest were low birth weight, preterm births, and small for gestational age. This study used structural equation modeling and trimester groupings to evaluate the relationship between air pollution and birth outcomes of pregnant residents. The latent variables of structural equation modeling yielded a significant B value of 0.35, indicating that exposure to the criteria pollutants in pregnancy may have a significant relationship to fetal morbidity. Exposure to criteria air pollutants in pregnancy is associated with fetal morbidity outcomes.


The subjective experience of using Ignatian meditation by male and female South African university students: an exploratory study.
This study is set out to examine the subjective experience of using the Ignatian method of meditation to reflect on and pray through Ruth 2. A group of male and female Theology students from the University of KwaZulu-Natal were invited to reflect upon/pray through Ruth 2 using Ignatian meditation. Following this exercise, participants were invited to participate in a focus group in which they shared their experience of this exercise, focusing particularly on some of the gendered aspects of the experience. The transcribed focus group material was subjected to a critical thematic analysis, in order to identify which core aspects of the experience of using this method of meditation and reflection were responsible for the reported subjective experiences. The analysis also included a comparison of the experience for men and women participating in this exercise, and the differential effect of various aspects of the exercise on men and women.


Biomarkers of DNA damage response improve in vitro micronucleus assays by revealing genotoxic mode of action and reducing the occurrence of irrelevant positive results.
We have previously described two flow cytometry-based in vitro genotoxicity tests: micronucleus (MN) scoring (MicroFlow®) and a multiplexed DNA damage response biomarker assay (MultiFlow®). Here, we describe a strategy for combining the assays in order to efficiently supplement MN analyses with a panel of biomarkers that comment on cytotoxicity (i.e. relative nuclei count, relative increased nuclei count, cleaved PARP-positive chromatin and ethidium monoazide-positive chromatin) and genotoxic mode of action (MoA; i.e. γH2AX, phospho-histone H3, p53 activation and polyploidy). For these experiments, human TK6 cells were exposed to each of 32 well-studied reference chemicals in 96-well plates for 24 continuous hours. The test chemicals were evaluated over a range of concentrations in the presence and absence of a rat liver S9-based metabolic activation system. MultiFlow assay data were acquired at 4 and 24 h, and micronuclei were scored at 24 h. Testing 32 chemicals in two metabolic activation arms translated into 64 a priori calls: 42 genotoxicants and 22 non-genotoxicants. The MN assay showed high sensitivity and moderate specificity (90% and 68%, respectively). When a genotoxic call required significant MN and MultiFlow responses, specificity increased to 95% without adversely affecting sensitivity. The dose-response data were analysed with PROAST Benchmark Dose (BMD) software in order to calculate potency metrics for each endpoint, and ToxPi software was used to synthesise the resulting lower and upper bound 90% confidence intervals into visual profiles. The BMD/ToxPi combination was found to represent a powerful strategy for synthesising multiple BMD confidence intervals, as the software output provided MoA information as well as insights into genotoxic potency.