The relationship between absolute lymphocyte count with PFS in patients with Hodgkin's lymphoma undergoing autologous hematopoietic cell transplant.
Previous reports in Hodgkin's lymphoma (HL) patients undergoing autologous hematopoietic cell transplantation (AHCT) have demonstrated a significant association between the absolute lymphocyte count at day 15 (ALC-15) with survival. To evaluate this finding further, we analyzed 146 patients with relapsed/refractory HL who underwent AHCT to evaluate the relationship between lymphocyte counts at apheresis and at two time points (days 15 and 90) after AHCT with PFS. We found no association between the ALC-15 and the ALC-90 with PFS. We found lymphocyte counts at apheresis and disease sensitive to salvage chemotherapy were predictive of PFS. In conclusion, our study does provide some support for the theory that the immune system may be important in disease control but further and more detailed studies in this area are required.


Skin cancer of the head and neck with perineural invasion: defining the clinical target volumes based on the pattern of failure.
To analyze patterns of failure in patients with head-and-neck cutaneous squamous cell carcinoma (HNCSCC) and clinical/radiologic evidence of perineural invasion (CPNI), in order to define neural clinical target volume (CTV) for treatment planning. Patients treated with three-dimensional (3D) conformal or intensity-modulated radiotherapy (IMRT) for HNCSCC with CPNI were included in the study. A retrospective review of the clinical charts, radiotherapy (RT) plans and radiologic studies has been conducted. Eleven consecutive patients with HNCSCCs with CPNI were treated from 2000 through 2007. Most patients underwent multiple surgical procedures and RT courses. The most prevalent failure pattern was along cranial nerves (CNs), and multiple CNs were ultimately involved in the majority of cases. In all cases the involved CNs at recurrence were the main nerves innervating the primary tumor sites, as well as their major communicating nerves. We have found several distinct patterns of disease spread along specific CNs depending on the skin regions harboring the primary tumors, including multiple branches of CN V and VII. These patterns and the pertinent anatomy are detailed in the this article. Predictable disease spread patterns along cranial nerves supplying the primary tumor sites were found in this study. Awareness of these patterns, as well as knowledge of the relevant cranial nerve anatomy, should be the basis for CTV definition and delineation for RT treatment planning.


The "ricochet effect" and prey capture in colonial spiders.
Increased prey capture efficiency in colonial spiders is a consequence of the "ricochet effect", as prey are captured after they bounce off several webs in succession. In this study, the prey capture of three species of colonial spiders in the genus Metepeira from Mexico are compared. These species, from different habitats, show varying levels of social organization (group size and withingroup spacing) that affect prey capture from ricochets. Metepeira sp. a (a presumed new species tentatively named atascadero) from desert grassland habitats, occur solitarily or in small groups, and gain little from prey ricochets: prey capture rates are low and variance in prey captured/spider is high. M. spinipes, from mesic agricultural sites, occur in groups of 10-150, and show a ricochet effect resulting in more and larger prey, and reduced variance in capture rate. M. incrassata, from tropical rainforest/agricultural sites, occur in large colonies of hundreds to thousands of individuals, and show a similar ricochet effect. The ricochet effect does not influence taxonomic composition of prey in either M. atascadero or M. spinipes, but does in tropical M. incrassata. This result, however, is primarily due to the capacity of certain taxa (eg., Lepidoptera), more common in the tropics, to escape more easily from spider webs. A comparison of prey capture efficiency of colonial M. incrassata with that of solitary M. atascadero shows that the ricochet effect provides an increase in efficiency across all size classes of prey.


Formation characteristics of bacteria and fungi in sewers: In terms of signal molecule generation.
Bio-metabolism of diverse communities is the main reason of water quality variation in sewers, and the signal molecule generation of communities is dementated to be the key regulation procedure for community metabolism. To reveal the mechanism of pollutant biotransformation in complex sewer environment, this study explored the formation of bacteria and fungi and the signal molecule transduction characteristics in a pilot sewer. In this study, several kinds of signal molecules that produced by bacteria and fungi (C4-HSL, C6-HSL, C8-HSL, farnesol and tyrosol) were detected along the formation process of sewer biofilms. The results showed that, in the early stage, bacterial AHLs signaling molecules are beneficial to the synthesis of EPS, providing a good material basis for the growth of bacterial flora. In addition, tyrosol stimulates the formation of embryonic tubes in yeast cells, further promoting the growth of hyphae. At the later stage, AHLs signaling molecules and tyrosol jointly promoted the growth of biofilms. In conclusion, it is precisely because of the coexistence of bacteria and fungi in the sewer system that the generated signal molecules can jointly promote the synthesis and growth of biofilms through different pathways, and have positive feedback on the biodegradation of various pollutants. Based on the exploration, the ecological patterns of bacterial-fungal communities in urban sewer system were proposed and it could improve the understanding on the pollutant transformation behaviors in sewers.


Impact of Preoperative Psychiatric Profile in Bariatric Surgery on Long-term Weight Outcome.
Conflicting results have been reported regarding the predictive value of preoperative psychological assessment and weight outcome after bariatric surgery. This might be attributed to different factors affecting early weight loss and long-term weight loss. Herein, we investigated whether preoperative psychiatric profile was associated with preoperative BMI and with both early (1 year) and long-term (5 years) weight loss after Roux-en-Y gastric bypass (RYGB). Prospective observational cohort study of patients undergoing RYGB between 2013 and 2019. Symptoms related to anxiety, depression, eating disorder, and alcohol use disorders were assessed by employing validated, specific psychometric tests (STAI-S/T, BDI-II, BITE, AUDIT-C) prior to surgery. Pre-operative BMI, early weight loss (1 year), and long-term weight evolution (up to 5 years) were registered. Two hundred thirty six patients (81% women) were included in the present study. Linear longitudinal mixed model showed a significant effect of preoperative high anxiety (STAI-S) on long-term weight outcome, after controlling for gender, age and type 2 diabetes. Patient with high preoperative anxiety score regained weight faster than those experiencing low anxiety (each year percent excess BMI loss (%EBMIL) - 4.02%, ± 1.72, p = 0.021). No other pre-operative psychiatric symptoms have been shown to have an impact on long-term weight loss. In addition, no significant association was found between any of the pre-operative psychiatric variables and pre-operative BMI, or early weight loss (%EBMIL) at 1-year post-RYGB. Herein we identified high anxiety score (STAI-S) as a predictor for long-term weight regain. Thus, long-term psychiatric surveillance of these patients and the development of tailored management tools could serve as a means to prevent weight regain.


Exosomal‑miR‑10a derived from colorectal cancer cells suppresses migration of human lung fibroblasts, and expression of IL‑6, IL‑8 and IL‑1β.
MicroRNAs (miRs) carried in exosomes serve an important role in the pre‑metastatic microenvironment and in intercellular interactions. However, the function of exosomal‑miR‑10a derived from primary colorectal cancer (CRC) cells on fibroblasts in the lung metastatic microenvironment of patients with CRC remains unclear. Reverse transcription‑quantitative PCR was performed using samples from patients with CRC, and demonstrated that the expression levels of miR‑10a were significantly lower in serum and cancer tissue samples from patients with CRC compared with in serum from healthy individuals and paired non‑cancerous tissues, respectively. In addition, the expression levels of miR‑10a were inversely associated with the invasion depth of CRC. Exosomal‑miR‑10a derived from CRC cells reduced the proliferative and migratory activities of primary normal human lung fibroblasts (NHLFs), and the expression levels of IL‑6, IL‑8 and IL‑1β in NHLFs. The present study provided insight into the phenotypic alterations of NHLFs induced by exosomal‑miR‑10a derived from CRC cells, which may aid understanding of the mechanism underlying the process of CRC lung metastasis.


Inhibition of the mevalonate pathway enhances carvacrol biosynthesis and DXR gene expression in shoot cultures of Satureja khuzistanica Jamzad.
Carvacrol is a major component of Satureja khuzistanica Jamzad (≤90%) that has significant antimicrobial and antioxidant properties. Considering the specific capabilities of S. khuzistanica to produce highly pure carvacrol, this plant is an important potential source of carvacrol that could address the abundant consumption and increasing demand for this monoterpene in current world markets. This research was performed to better understand the process of biosynthesis and accumulation of carvacrol in S. khuzistanica. Tests were performed on shoot cultures of S. khuzistanica in Linsmaier-Skoog (LS) medium treated with different concentrations of fosmidomycin (an inhibitor of the non-mevalonate pathway) and mevinolin (an inhibitor of the mevalonate pathway) for 21 days at the following concentrations: 0, 10, 25, 50, 75 and 100 μM. The present study demonstrated that the MEP pathway is the major pathway that provides IPP for the biosynthesis of carvacrol, and the expression and activity levels of the DXR enzyme have a critical effect on carvacrol biosynthesis. Surprisingly, Mevinolin at concentrations of 75 and 100 μM increased the carvacrol content and the DXR activity and gene expression in S. khuzistanica plantlets.


Rifampicin inhibits rotenone-induced microglial inflammation via enhancement of autophagy.
Mitochondrial and autophagic dysfunction, as well as neuroinflammation, are associated with the pathophysiology of Parkinson's disease (PD). Rotenone, an inhibitor of mitochondrial complex I, has been associated as an environmental neurotoxin related to PD. Our previous studies reported that rifampicin inhibited microglia activation and production of proinflammatory mediators induced by rotenone, but the precise mechanism has not been completely elucidated. BV2 cells were pretreated for 2h with rifampicin followed by 0.1μM rotenone, alone or in combination with chloroquine. Here, we demonstrate that rifampicin pretreatment alleviated rotenone induced release of IL-1β and IL-6, and its effects were suppressed when autophagy was inhibited by chloroquine. Moreover, preconditioning with 50μM rifampicin significantly increased viability of SH-SY5Y cells cocultured with rotenone-treated BV2 cells in the transwell coculture system. Chloroquine partially abolished the neuroprotective effects of rifampicin pretreatment. Rifampicin pretreatment significantly reversed rotenone-induced mitochondrial membrane potential reduction and reactive oxygen species accumulation. We suggest that the mechanism for rifampicin-mediated anti-inflammatory and antioxidant effects is the enhancement of autophagy. Indeed, the ratio of LC3-II/LC3-I in rifampicin-pretreated BV2 cells was significantly higher than that in cells without pretreatment. Fluorescence and electron microscopy analyses indicate an increase of lysosomes colocalized with mitochondria in cells pretreated with rifampicin, which confirms that the damaged mitochondria were cleared through autophagy (mitophagy). Taken together, the data provide further evidence that rifampicin exerts neuroprotection against rotenone-induced microglia inflammation, partially through the autophagy pathway. Modulation of autophagy by rifampicin is a novel therapeutic strategy for PD.


An HPLC chromatographic framework to analyze the β-cyclodextrin/solute complexation mechanism using a carbon nanotube stationary phase.
A carbon nanotube (CNT) stationary phase was used for the first time to study the β-cyclodextrin (β-CD) solute complexation mechanism using high performance liquid chromatography (HPLC). For this, the β-CD was added at various concentrations in the mobile phase and the effect of column temperature was studied on both the retention of a series of aniline and benzoic acid derivatives with the CNT stationary phase and their complexation mechanism with β-CD. A decrease in the solute retention factor was observed for all the studied molecules without change in the retention order. The apparent formation constant KF of the inclusion complex β-CD/solute was determined at various temperatures. Our results showed that the interaction of β-CD with both the mobile phase and the stationary phase interfered in the complex formation. The enthalpy and entropy of the complex formation (ΔHF and ΔSF) between the solute molecule and CD were determined using a thermodynamic approach. Negative enthalpies and entropies indicated that the inclusion process of the studied molecule in the CD cavity was enthalpically driven and that the hydrogen bonds between carboxylic or aniline groups and the functional groups on the β-CD rim play an important role in the complex formation.


The Identification of Three Cancer Stem Cell Subpopulations within Moderately Differentiated Lip Squamous Cell Carcinoma.
To identify and characterize cancer stem cells (CSCs) in moderately differentiated lip squamous cell carcinoma (MDLSCC). MDLSCC samples underwent 3,3-diaminobenzidine (DAB) immunohistochemical (IHC) staining for squamous cell carcinoma marker EMA, CSC marker CD44 and embryonic stem cell markers NANOG, octamer-binding transcription factor 4 (OCT4), spalt-like transcription factor 4 (SALL4), sex-determining region Y-box 2 (SOX2), and phosphorylated signal transducer and activator of transcription 3 (pSTAT3). Immunofluorescent IHC staining was performed on two MDLSCC samples. Western blotting (WB) was used to confirm the expression of the aforementioned proteins and their transcription activation was investigated using NanoString and RT-qPCR. IHC staining demonstrated the presence of (1) an EMA+/CD44+/SALL4+/NANOG+/pSTAT3+/SOX2+/OCT4- CSC subpopulation within the tumor nests (TNs); (2) a CD44+/SALL4+/NANOG+/pSTAT3+/SOX2+/OCT4- CSC subpopulation; and (3) a CD44+/SALL4+/NANOG+/pSTAT3+/SOX2+/OCT4+ CSC subpopulation within the stroma, between the TNs. NanoString and RT-qPCR confirmed the presence of mRNA for CD44, SALL4, STAT3, SOX2, and OCT4, and WB confirmed the presence of NANOG, pSTAT3, SOX2, and OCT4. This study demonstrates three putative CSC subpopulations within MDLSCC.


A protocol for tactile function assessment using JVP domes: Feasibility study and preliminary results.
Touch is a crucial sense for perceiving the spatial characteristics of objects. The JVP dome was developed to evaluate tactile spatial acuity using a grating orientation task. There were few studies depicting sequences and details for the entire task, including practice, training, and testing sessions. Therefore, we proposed and elaborated a protocol for the grating orientation task using the staircase method, which required fewer testing trials compared with the method of constant stimuli. Twenty-three healthy participants were enrolled in this experiment. The JVP domes with 11 different groove widths were used. Tactile discrimination thresholds were estimated using a two-down-one-up staircase method. The experiment comprised practice, training, and testing sessions, conducted by trained examiners who performed grating stimulation on participants' index fingerpads. All participants passed the required accuracy in the practice and training sessions. Eight transition points were obtained in the testing session for each participant. The tactile discrimination thresholds were determined from the last six transition points. We obtained the mean tactile discrimination threshold as 1.8 ± 0.75 mm (n = 23). The results demonstrated that the proposed protocol was successfully applied to assess tactile discrimination thresholds. The present study investigated the protocol of grating orientation tasks requiring a small number of testing trials with the assurance of the task quality. The feasibility study and preliminary results indicated the potentiality of this protocol for future clinical application.


Integrin-mediated invasion of Staphylococcus aureus into human cells requires Src family protein-tyrosine kinases.
Staphylococcus aureus, a common cause of nosocomial infections, is able to invade eukaryotic cells by indirectly engaging beta1 integrin-containing host receptors, whereas non-pathogenic Staphylococcus carnosus is not invasive. Here, we identify intracellular signals involved in integrin-initiated internalization of S. aureus. In particular, the host cell actin cytoskeleton and Src family protein-tyrosine kinases (PTKs) are essential to mediate S. aureus invasion. Src PTKs are activated in response to pathogenic S. aureus, but not S. carnosus. In addition, pharmacological and genetic interference with Src PTK function reduces bacterial internalization. Importantly, Src PTK-deficient cells are resistant to S. aureus invasion, demonstrating the essentiality of host Src PTKs in integrin-mediated uptake of this pathogen.


Mentorship in academic radiology: why it matters.
Mentorship plays a critical role in the success of academic radiologists. Faculty members with mentors have better career opportunities, publish more papers, receive more research grants, and have greater overall career satisfaction. However, with the increasing focus on clinical productivity, pressure on turn-around times, and the difficult funding climate, effective mentoring in academic radiology can be challenging. The high prevalence of "burnout" among radiologists makes mentorship even more important. This article reviews benefits and challenges of mentorship in academic radiology, discusses how to institute a faculty mentoring program, examines different types of mentoring, and reviews challenges related to diversity and inclusion.


Pathological Response in the Breast and Axillary Lymph Nodes after Neoadjuvant Systemic Treatment in Patients with Initially Node-Positive Breast Cancer Correlates with Disease Free Survival: An Exploratory Analysis of the GeparOcto Trial.
The conversion of initially histologically confirmed axillary lymph node-positive (pN+) to ypN0 after neoadjuvant systemic treatment (NAST) is an important prognostic factor in breast cancer (BC) patients and may influence surgical de-escalation strategies. We aimed to determine pCR rates in lymph nodes (pCR-LN), the breast (pCR-B), and both (tpCR) in women who present with pN+ BC, to assess predictors for response and the impact of pCR-LN, pCR-B, and tpCR on invasive disease-free survival (iDFS). Retrospective, exploratory analysis of 242 patients with pN+ at diagnosis from the multicentric, randomized GeparOcto trial. Of 242 patients with initially pN+ disease, 134 (55.4%) had a pCR-LN, and 109 (45.0%) a pCR-B. Of the 109 pCR-B patients, 9 (8.3%) patients had involved LN, and 100 (41.3%) patients had tpCR. Those with involved LN still had a bad prognosis. As expected, pCR-B and intrinsic subtypes (TNBC and HER2+) were identified as independent predictors of pCR-LN. pCR-LN (ypN0; hazard ratio 0.42; 95%, CI 0.23-0.75; p = 0.0028 for iDFS) was the strongest independent prognostic factor. In initially pN+ patients undergoing NAST, the conversion to ypN0 is of high prognostic value. Surgical axillary staging after NAST is still essential in these patients to offer tailored treatment.


Mass spectrometric detection of cross-linked fatty acids formed during radical-induced lesion of lipid membranes.
A mass spectrometric method is described for the quantitative determination of dimers of polyunsaturated fatty acids (PUFA) formed in the hepatic endoplasmic reticulum of rats upon inhalation of tetrachloromethane. The results show that dimers account for a considerable fraction of microsomal PUFA which disappear during CCl4 metabolism. Cross-linking of the membrane lipids of the endoplasmic reticulum seems to be a significant process with respect to cell toxicity.


Activation of the adenosine A1 receptor in the lumbosacral spinal cord improves bladder overactivity in rats with cystitis induced by cyclophosphamide.
To investigate the effect of intrathecal administration of CCPA, an adenosine A1 receptor agonist, on voiding function in rats with cystitis induced by cyclophosphamide (CYP). Thirty 8-week-old Sprague Dawley rats were randomly divided into a control group (n = 15) and a cystitis group (n = 15). Cystitis was induced by a single intraperitoneal injection of CYP (200 mg/kg, dissolved in physiological saline) in rats. Control rats were injected intraperitoneally with physiological saline. The PE10 catheter reached the level of L6-S1 spinal cord through L3-4 intervertebral space for intrathecal injection. Forty-eight hours after intraperitoneal injection, urodynamic tests were conducted to observe the effect of intrathecal administration of 10% dimethylsulfoxide (vehicle) and 1 nmol CCPA on micturition parameters, including basal pressure (BP), threshold pressure (TP), maximal voiding pressure (MVP), intercontraction interval (ICI), voided volume (VV), residual volume (RV), bladder capacity (BC), and voiding efficiency (VE). Histological changes of the bladder of cystitis rats were studied through hematoxylin-eosin staining (HE staining). Moreover, Western blot and immunofluorescence were used to study the expression of adenosine A1 receptor in the L6-S1 dorsal spinal cord in both groups of rats. HE staining revealed submucosal hemorrhage, edema, and inflammatory cell infiltration in the bladder wall of cystitis rats. The urodynamic test showed significant increase in BP, TP, MVP and RV in cystitis rats, while ICI, VV, BC and VE decreased significantly, indicating bladder overactivity. CCPA inhibited the micturition reflex in both control and cystitis rats, and significantly increased TP, ICI, VV, BC, and VE, but had no significant effect on BP, MVP and RV. Western blot and immunofluorescence showed that there was no significant difference in the expression of adenosine A1 receptor in the L6-S1 dorsal spinal cord between the control and cystitis rats. The findings of this study suggest that intrathecal administration of the adenosine A1 receptor agonist CCPA alleviates CYP-induced bladder overactivity. Furthermore, our results indicate that the adenosine A1 receptor in the lumbosacral spinal cord may be a promising target for treatment of bladder overactivity.


Antibody domain mutants demonstrate autonomy of the antigen binding site.
We have constructed derivatives of a lambda I light chain-bearing anti-(4-hydroxy,3-nitrophenyl)acetyl (NP) antibody which have the V regions exchanged between heavy chains and light chains of the kappa or lambda I type. These antibodies are assembled and secreted normally, and bind haptenic and macromolecular ligands like the wild-type; similar results are obtained for monovalent heterodimers of VHCL and lambda I light chains. The observed independence of the binding site from the constant region context argues against a role of longitudinal interactions between constant and variable domains in antigen recognition, and therefore against cooperativity between binding sites.


Who's the victim: women, control and consciousness.
It is contended that newspaper coverage of rape can be biased against women, so retarding the progress of rape law reform in America. The extent of coverage and the slant put on a particular case by a newspaper in Duluth, Minnesota, is closely examined in support of the thesis.


US Regional Changes in Racial/Ethnic Disparities in HIV Diagnoses Among Women in the United States, 2012 and 2017.
Racial/ethnic and geographic disparities in HIV diagnosis rates exist among women in the United States. Black/African American women are disproportionately affected; rates are highest in the South and Northeast. Monitoring progress towards eliminating disparities in HIV diagnosis rates among women is a national HIV prevention goal. To illustrate the performance of different measures of disparities, we compared 2012 and 2017 HIV diagnosis rates among adult and adolescent females by race/ethnicity and geographic region. We used HIV surveillance data for diagnoses and five absolute and three relative measures of disparity. The absolute disparity decreased in each region; the relative disparity decreased with the exception of one measure in the Northeast and South. Despite progress, disparities in HIV diagnosis rates among women remain. Appropriate strategies to measure progress and contextualize findings are needed.


Use of MRI in the diagnosis and prognosis of acute necrotizing encephalopathy in a Chinese teenager: A case report.
Acute necrotizing encephalopathy (ANE) is a rapidly progressing disease associated with frequent neurologic sequelae and has poor prognosis. Currently, the diagnosis and treatment of ANE rely on neuroradiologic findings and offering supportive care. Here, we report the successful treatment of a teenager diagnosed with ANE using combination of high-dose methylprednisolone and oseltamivir. The patient, a 15-year-old female, presented with impaired consciousness and seizures secondary to acute upper respiratory tract infection. A series of brain magnetic resonance images (MRIs) were obtained toward establishing a possible diagnosis. Based on the history of presenting illness and subsequent brain MRI scans, the patient was diagnosed to be suffering from ANE. Following the diagnosis, the patient was placed on therapy comprising of high-dose methylprednisolone and oseltamivir. After treatment with methylprednisolone and oseltamivir for 15 days, the patient recovered nearly completely from ANE as confirmed by subsequent brain MRI scans. No complications or other emerging clinical symptoms were noted for the duration of follow-up that lasted 6 months. Contrary to common reports, ANE can occur beyond pediatric populations and its treatment should not be restricted to supportive care. Our case suggests that the use of high-dose corticosteroids and oseltamivir leads to promising prognosis.


Perfectly Encoding π-Conjugated Anions in the RE5 (C3 N3 O3 )(OH)12 (RE=Y, Yb, Lu) Family with Strong Second Harmonic Generation Response and Balanced Birefringence.
Nonlinear optical (NLO) crystal, which simultaneously exhibits strong second-harmonic-generation (SHG) response and desired optical anisotropy, is a core optical material accessible to the modern optoelectronics. Accompanied by strong SHG effect in a NLO crystal, a contradictory problem of overlarge birefringence is ignored, leading to low frequency doubling efficiency and poor beam quality. Herein, a series of rare earth cyanurates RE5 (C3 N3 O3 )(OH)12 (RE=Y, Yb, Lu) were successfully characterized by 3D electron diffraction technique. Based on a "three birds with one stone" strategy, they enable the simultaneous fulfillment of strong SHG responses (2.5-4.2× KH2 PO4 ), short UV cutoff (ca. 220 nm) and applicable birefringence (ca. 0.15 at 800 nm) by the introduction of rare earth coordination control of π-conjugated (C3 N3 O3 )3- anions. These findings provide high-performance short-wavelength NLO materials and highlight the exploration of cyanurates as a new research area.


Ultrasonically determined elasticity and cortical density in canine femora after hip arthroplasty.
Effects of canine hip replacement (with a porous-coated femoral component) on the material properties of surrounding cortical bone were evaluated. The hypotheses were: (1) after four months of implantation, mechanical properties of the cortex would change, and (2) a collared implant would be associated with smaller changes than a collarless design. Unilateral total hip arthroplasty was performed in 15 mixed-breed dogs. Nine received a collared and six received a collarless femoral component. Four months after implantation, longitudinal ultrasonic wave propagation velocities and bone mineral densities (from dual energy X-ray absorptiometry) were measured in harvested femora and used to calculate the axial elastic constitutive coefficients for the cortex surrounding the implants. Results showed no difference in bone elasticity or bone density between collared and collarless designs. Significant velocity decreases from control values (p < 0.0001) were noted in all implanted femora at four months. Bone mineral densities also displayed decreased values after four months of implantation (p < 0.0145). Elastic coefficients were consistently less after four months of implantation when compared to control values (p < 0.0001). This alteration in material properties would affect load transfer into the implanted femur via the increased disparity between implant and bone stiffnesses regardless of the component design. Significant differences in the elastic coefficients between implanted and control femora support hypothesis 1. However, no group differences were found between collared and collarless implantations; thus, the study does not support hypothesis 2.


Cultivation-based assessment of lysogeny among soil bacteria.
Lysogeny has long been proposed as an important long-term maintenance strategy for autochthonous soil bacteriophages (phages). Whole genome sequence data indicate that prophage-derived sequences pervade prokaryotic genomes, but the connection between inferred prophage sequence and an active temperate phage is tenuous. Thus, definitive evidence of phage production from lysogenic prokaryotes will be critical in determining the presence and extent of temperate phage diversity existing as prophage within bacterial genomes and within environmental contexts such as soils. This study optimized methods for systematic and definitive determination of lysogeny within a collection of autochthonous soil bacteria. Twenty bacterial isolates from a range of Delaware soil environments (five from each soil) were treated with the inducing agents mitomycin C (MC) or UV light. Six isolates (30%) carried inducible temperate phages as evidenced by an increase in virus direct counts. The magnitude of induction response was highly dependent upon specific induction conditions, and corresponding burst sizes ranged from 1 to 176. Treatment with MC for 30 min yielded the largest induction responses for three of the six lysogens. Morphological analysis revealed that four of the lysogens produced lambda-like Siphoviridae particles, whereas two produced Myoviridae particles. Additionally, pulsed-field gel electrophoresis data indicated that two of the six lysogens were polylysogens, producing more than one distinct type of phage particle. These results suggest that lysogeny is relatively common among soil bacteria.


Early Metabolic Improvement After Bariatric Surgery: The First Steps Toward Remission of Type 2 Diabetes.
The introduction of bariatric surgery into clinical practice in the 1980s was followed by a relatively long watch-and-wait period before the very rapid accumulation of scientific literature, over the past decade, concerning its clinical effectiveness and safety and its mechanisms of action in the treatment of obesity. These surgical procedures now emerge as the most effective therapeutic modality to induce long-term remission of type 2 diabetes. Recent research has shed light on the potential mechanisms leading to the profound improvement of glucose homeostasis following most bariatric surgery procedures. These mechanisms can be classified as weight loss dependent and independent, both playing sequential and then synergistic antidiabetes roles. Many groups, including our own, have contributed to our understanding of the relative roles of these mechanisms at differing time periods following these procedures. Here we summarize what we currently know about the mechanisms underlying the very rapid, weight loss-independent improvement in glucose homeostasis after bariatric surgery. Beyond its impact in the field of bariatric surgery, this new knowledge about the very rapid in vivo "reverse engineering" of type 2 diabetes actually provides unique insights into the intricate and complex mechanisms linking nutrition and obesity with the development of this disease.


Circ-SFMBT2 sponges miR-224-5p to induce ketamine-induced cystitis by up-regulating metadherin (MTDH).
There is increasing evidence that circular RNAs (circRNAs) play significant roles in various biological processes, yet few reports have examined their roles and molecular mechanisms in ketamine-induced cystitis (KIC). This study examines the possible molecular mechanisms underlying the circRNA-microRNA-mRNA regulatory network in the development of KIC. Transcriptome data were collected, and bioinformatics analysis was conducted to create a circRNA-miRNA-mRNA regulatory network (ceRNA network) associated with the occurrence of KIC. Human bladder epithelial cells (SV-HUC-1) were used in in vitro cell assays. The binding affinity among circ-SFMBT2, miR-224-5p, and Metadherin (MTDH) was identified. To investigate the effects of circ-SFMBT2/miR-224-5p/MTDH on bladder function, KIC mouse models were induced by intraperitoneal injection of ketamine, and gain- or loss-of-function experiments were conducted. Our results demonstrate that MTDH may be a key gene involved in the occurrence of KIC. Both bioinformatics analysis and in vitro cell assays verified that circ-SFMBT2 can competitively bind to miR-224-5p, and miR-224-5p can target and inhibit MTDH. In the bladder tissues of KIC mice, circ-SFMBT2 and MTDH were up-regulated, while miR-224-5p was down-regulated. Animal experiments further confirmed that circ-SFMBT2 can up-regulate MTDH expression by sponging miR-224-5p, thereby exacerbating bladder dysfunction in KIC mice. This study proved that circ-SFMBT2 up-regulates MTDH by competitively binding to miR-224-5p, thereby exacerbating the bladder dysfunction of KIC.


Understanding Market Size and Reporting Gaps for Paediatric TB in Indonesia, Nigeria and Pakistan: Supporting Improved Treatment of Childhood TB in the Advent of New Medicines.
We sought to understand gaps in reporting childhood TB cases among public and private sector health facilities (dubbed "non-NTP" facilities) outside the network of national TB control programmes, and the resulting impact of under-reporting on estimates of paediatric disease burden and market demand for new medicines. Exploratory assessments were carried out in Indonesia, Nigeria and Pakistan, reaching a range of facility types in two selected areas of each country. Record reviews and interviews of healthcare providers were carried out to assess numbers of unreported paediatric TB cases, diagnostic pathways followed and treatment regimens prescribed. A total of 985 unreported diagnosed paediatric TB cases were identified over a three month period in 2013 in Indonesia from 64 facilities, 463 in Pakistan from 35 facilities and 24 in Nigeria from 20 facilities. These represent an absolute additional annualised yield to 2013 notifications reported to WHO of 15% for Indonesia, 2% for Nigeria and 7% for Pakistan. Only 12% of all facilities provided age and sex-disaggregated data. Findings highlight the challenges of confirming childhood TB. Diagnosis patterns in Nigeria highlight a very low suspicion for childhood TB. Providers note the need for paediatric medicines aligned to WHO recommendations. This study emphasises the impact of incomplete reporting on the estimation of disease burden and potential market size of paediatric TB medicines. Further studies on "hubs" (facilities treating large numbers of childhood TB cases) will improve our understanding of the epidemic, support introduction efforts for new treatments and better measure markets for new paediatric medicines.


Analysis of incidence data in developmental toxicity studies: Statistical tests to account for litter effects in fetal defect data.
When analyzing fetal defect incidence in laboratory animal studies, correlation in responses within litters (i.e., litter effects) can lead to increased false-positive rates if litter effects are not incorporated into the analysis. Studies of fetal defects require analysis methods that are robust across a broad range of defect types, including those with zero or near-zero incidence rates in control groups. A simulation study compared power and false-positive rates for six approaches across a range of background defect rates and litter size distributions. Statistical methods evaluated included ignoring the litter effect as well as parametric and nonparametric approaches based on litter proportions, generalized linear mixed models (GLMMs), the Rao-Scott Cochran-Armitage (RSCA) trend test, and a modification to the RSCA (mRSCA) introduced here to improve estimation at low background rates. These methods were also applied to a common and a rare defect from two prenatal developmental toxicology studies conducted by the National Toxicology Program (NTP). At background defect rates of 1%, the mRSCA and parametric litter proportion methods provided gains in power over the nonparametric litter proportion method, the GLMM method, and the RSCA method. Simulations involving litter loss in high-dose groups showed loss of power for both litter proportion methods. The mRSCA test developed here compares favorably with other litter-based approaches and is robust across a range of background defect rates and litter size distributions, making it a practical choice for prenatal developmental toxicology studies involving both common and rare fetal defects.


Selective Acylation of Proteins at Gly and Lys in His Tags.
The chemical modification of proteins is of great importance in chemical biology, biotechnology, and for the production of modified biopharmaceuticals, as it enables introduction of fluorophores, biotin, half-life extending moieties, and more. We have developed two methods that use poly-His sequences to direct the highly selective acylation of proteins, either at the N-terminus or at a specific Lys residue. For the former, we used an N-terminal Gly-His6 segment (Gly-His tag) that directed acylation of the N-terminal Nα -amine with 4-methoxyphenyl esters, resulting in stable conjugates. Next, we developed the peptide sequences Hisn -Lys-Hism (Lys-His tags) that direct the acylation of the designated Lys Nϵ -amine under mild conditions and with high selectivity over native Lys residues. Both the Gly-His and Lys-His tags maintain the capacity for immobilized metal ion affinity chromatography. We have demonstrated the robustness of these methods by attaching different moieties such as azides, fluorophores, and biotin to different proteins, including antibodies.


[Paraneoplastic neurologic degeneration revealing ovarian cancer recurrence].
Paraneoplastic neurologic degeneration (PND) is characterized by acute and subacute onset neurological syndrome associated with active or with subclinical cancer. It is rare but early diagnosis can improve the neurological and carcinological prognosis. Among the PNDs it is possible to distinguish subacute cerebellar degeneration often associated with gynecological or breast cancer. We report the case of a 50-year old female patient on follow-up for ovarian adenocarcinoma treated with surgery and whose recurrence was detected due to anti-Yo antibody-positive subacute cerebellar degeneration.


Laurence-Moon-Biedl syndrome accompanied by congenital hepatic fibrosis.
A 33 year old woman with mental deficiency, retinitis pigmentosa, obesity, and parental consanguinity (heredity) was diagnosed as having Laurence-Moon-Biedl syndrome. She also had diabetes mellitus, slight hepatic dysfunction, and hepatomegaly. Liver biopsy showed perilobular fibrosis and bile duct proliferation with cystic dilatation; these findings are consistent with those of congenital hepatic fibrosis.


A possible mechanism for the peroxidation of lipids due to chronic ethanol ingestion.
The effects of chronic ethanol ingestion on NADPH-oxidase and on the NADPH-catalyzed peroxidation of lipids in rat liver microsomes have been studied. It was demonstrated that the rates of NADPH oxidation, of oxygen consumption, and of malondialdehyde formation increased significantly above control values after one month of ethanol ingestion. Further, the fatty acid composition of these microsomes revealed a decrease in arachidonate and in the C22 polyenes. Also, the energies of activation for the formation of malondialdehyde increased in the microsomes from the ethanol-treated animals. These results were interpreted to mean that ethanol ingestion had induced changes in the microsomal membranes such that additional or alternate, possibly abnormal, pathways for lipid peroxidation were functional. Finally, these data suggest a mechanism whereby chronic ethanol ingestion inhances the production of lipid peroxides via the microsomal-catalyzed oxidation of NADPH.


Scales and assessments of sexual dysfunction.
Sexual dysfunction is a very frequent non-motor symptom in Parkinson's disease (PD). However, patients are often reluctant to declare their sexual problems and many clinicians do not inquire about them during routine visits. The use of validated rating scales and questionnaires allows overcoming these difficulties, characterizing the nature and causes of the patient's sexual dysfunction, and helping to implement and monitor the most adequate interventions. There is a wide range of instruments available for assessing sexual dysfunction in PD, including generic and specific ones. In this chapter, we review the most used rating scales and questionnaires, with a description of its components, characteristics and psychometric attributes.


Cytological evidence of male heterogamety in sex determination of Telmatoscopus albipunctatus (Diptera: Psychodidae).
Telmatoscopus albipunctatus is polymorphic for several polytene chromosome bands. In examining the inheritance of a polymorphic heterochromatin-like band in chromosome IV we verified that it is inherited like a sex-linked factor. There are two types of chromosome IV in regard to this band: one bears a very thick heterochromatin-like band (H+), and the other bears a thinner corresponding band (H-). Three kinds of combinations are found in our stocks: H+H+, H+H- and H-H-. All three combinations can be found in females; however, in males, only the combinations H+H- and H-H- are found. Through specific crosses, it was concluded that the sex determining factor is located in chromosome IV in close vicinity to these bands.


Molecular detection and characterization of noroviruses in river water in Thailand.
Norovirus (NoV) generally exists as a mixture of multiple genotype variants in nature. However, there has been no published report monitoring NoV in natural settings in Thailand. To obtain information on mixed presence of the NoV RNA genome, we conducted viral genome analysis of 15 water specimens collected from five sites in a river near Bangkok between August 2013 and August 2014. The number of viral RNA copies per specimen declined progressively from the most upstream to the most downstream site. Following direct nucleotide sequencing of the PCR products, we obtained three partial genome sequences of the NoV GI strain and 13 partial genome sequences of the NoV GII strains. Phylogenetic analysis indicated the presence of four GII.4 variant groups pro-circulated after the Den Haag_2006b, New Orleans_2009 and Sydney_2012 outbreaks. On the other hand, only GI.4 was observed from the specimens collected on April, 2014. These results indicated that multiple genogroups and genotypes of noroviruses are present and are circulating in the natural environment in Thailand as in other countries. Our study provides comprehensive information on the occurrence of new variants. Our study is the first paper that multiple genogroups and genotypes of norovirus exist, and are circulating in the river water near Bangkok, Thailand. Phylogenetic analysis indicated the presence of four GII.4 variant groups pro-circulated after the Den Haag_2006b, New Orleans_2009 and Sydney_2012 that caused outbreaks in the world. Continued research will be essential for understanding the natural history of NoV and the control of future outbreaks.


["Biloma": its diagnosis and treatment by percutaneous echo-guided evacuation].
The term "biloma" describes an intra-abdominal bile collection secondary to traumatic or iatrogenic injury of the biliary tree. We present a case of biloma treated by guided percutaneous needle aspiration.


Production of bioactive gastrin from the non-endocrine cell lines CHO and COS-7.
We made a mutated progastrin cDNA construct that contains a cleavage site (-Arg(-4)-Arg(-3)-Lys(-2)-Arg-1) specific for the Kex2-like endoprotease furin, located ahead of the bioactive gastrin. For expressing the mutated progastrin cDNA, we used two non-endocrine cell lines, CHO and COS-7. CHO cells exhibit amidating enzyme activity and levels of amidation enzyme mRNA as high as those in the pituitary-derived endocrine cell line GH3, whereas COS-7 cells have far less amidating activity and lower amounts of mRNA. Mutant progastrin-expressing CHO cells produced mostly amidated gastrin. Gel filtration showed the size of this gastrin corresponded to that of the synthetic human gastrin-17. In contrast, COS-7 cells produced glycine-extended gastrin and only a small amount of amidated gastrin. The difference in the amount of amidated gastrin products produced by the two non-endocrine cell lines is due to differing amounts of the amidation enzyme contained in each cell line.


Distributed H∞ filtering of replay attacks over sensor networks.
A distributed H∞ filtering issue is addressed in this paper for discrete-time nonlinear systems in the face of replay attacks over sensor networks, where an indicator variable is introduced to describe whether a replay attack is launched by the adversaries. First, an interesting pattern dependent on three parameters including a time-varying one is established to account for the temporal behavior of malicious attacks. Then, taking advantage of such a model, the resulting filter dynamic is transformed into a switching system with a subsystem with time-varying delays. By means of the famous switching system theory, a sufficient condition guaranteeing the H∞ performance is derived to disclose the tolerant attack condition, that is, the attack-active duration and proportion. In addition, the applicable filter gains are achieved with the aid of the solutions of matrix inequalities. Finally, an example is purposively given to adequately illustrate the availability of the developed secure filtering strategy.


Enhanced acoustic startle responding in rats with radiation-induced hippocampal granule cell hypoplasia.
Irradiation of the neonatal rat hippocampus reduces the proliferation of granule cells in the dentate gyrus and results in locomotor hyperactivity, behavioral perseveration and deficits on some learned tasks. In order to address the role of changes in stimulus salience and behavioral inhibition in animals with this type of brain damage, irradiated and normal rats were compared in their startle reactions to an acoustic stimulus. A portion of the brain of 10 rats was exposed to a fractionated total dose of 13 Gy during the first 16 days post partum. This procedure produced selective hypoplasia (91% reduction) of the granule cells in the hippocampal dentate gyrus. Other rats (N = 10) were sham irradiated. Sudden tones were presented to each adult rat at a rate of 1 every 30 s (spaced trials) during an initial 10-min session and 1 every 15 s (massed trials) during a subsequent session. Irradiated rats startled with a consistently higher amplitude than controls and were more likely to exhibit startle responses. These animals with hippocampal damage also failed to habituate to the startle stimulus and, under certain circumstances, showed potentiated startle responses after many tone presentations.


Evaluation of the suitability of six host genes as internal control in real-time RT-PCR assays in chicken embryo cell cultures infected with infectious bursal disease virus.
Infectious bursal disease virus (IBDV) can cause disease in chickens characterized by immunosuppression and high mortality. Currently, real-time RT-PCR has been used to quantitate virus-specific RNA and to better understand host response to infection. However, normalization of quantitative real-time RT-PCR is needed to a suitable internal control. We thus investigated the expression pattern of six chicken genes, including beta-actin, 28S rRNA, 18S rRNA, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), TATA box-binding protein (TBP) and beta-2-microglobulin, in chicken embryo (CE) cell cultures following a 7-day IBDV infection. The CE cells were inoculated with various multiplicity of infection (MOI) of IBDV vaccine strain Bursine-2, the expression of genes was measured by quantitative real-time PCR-based on cDNA synthesized from either normalized (100 ng) or non-normalized (10 microl) total RNA. The results showed that beta-actin, 28S rRNA, 18S rRNA and GAPDH were the most constantly expressed genes, while TBP and beta-2-microglobulin were markedly induced during the infection course. Of these constant expressed genes, 28S rRNA and 18S rRNA are highly expressed; beta-actin intermediately expressed and GAPDH had a lower expression level in CE cell cultures. Also, beta-actin showed no significant variation in both normalized and non-normalized assays and virus dose-independent of inoculation, while other genes did. beta-Actin was further successfully used as an internal control to quantitate Bursine-2 virus-specific RNA load in CE cell cultures. Thus, beta-actin was suggested as a suitable internal control in studying gene expression as well as virus-specific RNA load in CE cell after IBDV infection.


When Painlevé-Gullstrand coordinates fail.
Painlevé-Gullstrand coordinates, a very useful tool in spherical horizon thermodynamics, fail in anti-de Sitter space and in the inner region of Reissner-Nordström. We predict this breakdown to occur in any region containing negative Misner-Sharp-Hernandez quasilocal mass because of repulsive gravity stopping the motion of PG observers, which are in radial free fall with zero initial velocity. PG coordinates break down also in the static Einstein universe for completely different reasons. The more general Martel-Poisson family of charts, which normally has PG coordinates as a limit, is reported for static cosmologies (de Sitter, anti-de Sitter and the static Einstein universe).


Continuous cisplatin (24-hour) and 5-fluorouracil (120-hour) infusion in recurrent head and neck squamous cell carcinoma.
Cisplatin and 5-fluorouracil (5-FU) has been reported to be one of the most active chemotherapeutic regimens in recurrent head and neck squamous cell carcinoma. In this study, 21 patients with recurrent head and neck squamous cell carcinoma received a combination of cisplatin given as a 100 mg/m2 continuous infusion over 24 hours and 5-FU given as a 1000 mg/m2 24-hour continuous infusion for 120 hours. Toxicity was evaluated in all patients, and response and survival were evaluated 20 patients. There were two complete remissions (10%) and three partial remissions (15%) for a major response of 25%. Overall survival for the complete responders was 79+ and 61+ weeks, respectively. Median survival for all patients was 36 weeks. Toxicity consisted of moderate to severe nausea and vomiting in 14 patients (66%), mucositis in 14 patients (66%), granulocytopenia of less than 1000/microliter in 11 patients (52%), objective peripheral neuropathy in one patient (4.7%), and nephrotoxocity in one patient (4.7%). We conclude that the efficacy of 24-hour cisplatin infusion and 120-hour 5-FU infusion in the treatment of recurrent head and neck squamous carcinoma is not superior to the efficacy of single agent trials reported in the literature.


Objective specification of tritanopic confusion lines using visual evoked potentials.
The minimum distinct border (MDB) between different isoluminant hues of a bipartite field was set subjectively by adjustment and then according to a 3-point rating allowing determination of the S-cone specific (tritanopic) axis. This rating was compared with visual evoked potentials (VEPs) generated by coarse, isoluminant gratings, modulated along the same chromatic axes. Psychophysically determined tritanopic gratings elicited monophasic onset VEPs with the longest latency for each subject. Departure from this axis produced additional earlier negative components (reflecting additional response mechanisms). Colour-selective VEPs can, therefore, objectively specify tritanopic confusion lines with a comparable degree of accuracy to MDB judgements.


TOX and ADIPOQ Gene Polymorphisms Are Associated with Antipsychotic-Induced Weight Gain in Han Chinese.
To find the genetic markers related to the antipsychotic-induced weight gain (AIWG), we analyzed associations among candidate gene single-nucleotide polymorphisms (SNPs) and quantitative traits of weight changes and lipid profiles in a Chinese Han population. A total of 339 schizophrenic patients, including 86 first-episode patients (FEPs), meeting the entry criteria were collected. All patients received atypical antipsychotic drug monotherapy and hospitalization and were followed for 12 weeks. Forty-three SNPs in 23 candidate genes were calculated for quantitative genetic association with AIWG, performed by PLINK. The TOX gene SNP rs11777927 (P = 0.009) and the ADIPOQ gene SNP rs182052 (P = 0.019) were associated with AIWG (in body mass index, BMI). In addition, the BDNF SNP rs6265 (P = 0.002), BDAF SNP rs11030104 SNP (P = 0.001), and ADIPOQ SNPs rs822396 (P = 0.003) were significantly associated with the change of waist-to-hip ratio (WHR) induced by atypical antipsychotics. These results were still significant after age and gender adjustments. These findings provide preliminary evidence supporting the role of TOX, ADIPOQ and BDNF in weight and WHR gain induced by atypical antipsychotics.


Chromosome banding study of the Cornelia De Lange syndrome.
Chromosome studies were performed on 13 patients with the Cornelia de Lange syndrome. With the technique of chromosome banding analysis, no chromosomal abnormalities were found.


Differentiating thymic epithelial tumors from mediastinal lymphomas: preoperative nomograms based on PET/CT radiomic features to minimize unnecessary anterior mediastinal surgery.
Clinical feasibility nomograms were developed to facilitate the differentiation between thymic epithelial tumors (TETs) and mediastinal lymphomas (MLs), aiming to minimize the occurrence of non-therapeutic thymectomy. A total of 255 patients diagnosed with TETs or MLs underwent pre-treatment 18F-FDG PET/CT. Comprehensive clinical and imaging data were collected, including age, gender, lactate dehydrogenase (LDH) level, pathological results, presence of myasthenia gravis symptoms, B symptoms, mass size, location, morphology, margins, density, and metabolic parameters derived from PET/CT. Radiomic features were extracted from the region of interest (ROI) of the primary lesion. Feature selection techniques were employed to identify the most discriminative subset of features. Machine learning methods were utilized to build candidate models, which were subsequently evaluated based on their area under the curve (AUC). Finally, nomograms were constructed using the optimal model to provide a clinical tool for improved diagnostic accuracy. The performance of the radiomic models was evaluated by their calibration, discrimination, and clinical utility. Several independent risk factors were identified for distinguishing TETs from MLs, including average standardized uptake value (SUVavg), LDH, age, mass size, and radiomic score (rad-score). Significance was observed in differentiating the two types of tumors based on these factors. The best clinical efficacy was demonstrated by the combined model, with an impressive AUC of 0.954. Decision curve analysis and calibration curves indicated that the combined model was clinically advantageous for discriminating TETs from MLs. Besides, the results of external validation showed a sensitivity of 0.8 and a specificity of 0.78. Preoperatively, the differentiation of TETs from MLs can be facilitated by the utilization of the combined clinical information and radiomics model. This approach holds promise in minimizing the occurrence of unnecessary anterior mediastinal surgeries.


Defining the role of proton therapy in the optimal management of paediatric patients in Australia and New Zealand.
Optimal management of paediatric patients with tumours may include radiation therapy. Proton therapy, in theory, should achieve superior outcomes. For children referred overseas, multiple factors are taken into consideration. The purpose of this article is to provide context to current decision making. The MEDLINE, EMBASE and PubMed databases were searched for relevant literature. The delivery of proton therapy is in evolution. Tissue homogeneity, movement and anatomical changes all present a greater challenge for proton therapy compared with photon therapy. Many dosimetry studies are relying on historical data for cost-benefit analyses that do not accurately reflect contemporary photon therapy. The low dose regions generally do not create significant toxicity, whereas moderate dose regions can be reduced by different techniques such as stereotactic radiotherapy and brachytherapy. Neuro-cognitive and neuro-endocrine toxicities are associated with the greatest health cost, so the greatest gain is for tumours within or abutting the central nervous system. Proton therapy does not eliminate the risk of second malignancy. The benefits of proton therapy must be weighed against not just the estimated impact of low and moderate radiation doses on the developing child but the disruptions to the child, and family life. Relative contraindications to proton therapy include when the relevant late toxicities relate to the high radiation dose region, when the tumour volumes encompass whole body sections and when the target is imprecise. Children with base of skull tumours or an inherited risk of cancer (e.g. those with p53 or Rb1 genes) should be considered for proton therapy.


Epiglottitis and pulmonary oedema in children.
We have presented three patients with epiglottitis who developed pulmonary oedema during the course of treatment with nasotracheal intubation and antibiotics. The exact mechanism for the development of pulmonary oedema in these patients is not known. Possible mechnisms are changed in the physical factors controlling the movement of fluids across the capillary-alveolar membrane, transitory bacteraemia and endotoxinaemia, or myocardial depression by the antibiotics and the anaesthetic agent. The pulmonary oedema had a benign course and responded to mechanical ventilation and increased airway pressure.


Tf2 O-Catalyzed Tandem Cyclization/Trifluoromethylselenolation of Alkynes for Synthesis of CF3 Se-Containing Heterocycles.
Herein, the tandem synthesis of various CF3 Se-containing heterocyclic compounds has been developed, using Tf2 O as the catalyst and trifluoromethyl selenoxides as the electrophilic trifluoromethylselenolation reagents. This process is characterized by its mild conditions, ease of operation, and good functional group compatibility. A variety of alkynes could be transferred into CF3 Se-containing indoles, benzofurans, benzothiophenes, isoquinolines and chromenes in good yields. A key step involving the formation of the electrophilic CF3 Se species was proposed.


Superior Capsular Reconstruction with Fascia Lata Allograft for Irreparable Supraspinatus Tendon Tears.
Superior capsular reconstruction is a recently described procedure for the treatment of irreparable supraspinatus tendon tears. Graft options that have been previously described include autogenous fascia lata and decellularized dermal graft. No studies were published with the use of fascia lata allograft. The purpose of this technical note is to describe the surgical technique of superior capsular reconstruction using fascia lata allograft. The procedure is performed by arthroscopic visualization, with the patient positioned in the lateral decubitus position. The authors describe a technique based on the use of a double-pulley knot in the glenoid and greater tuberosity, facilitating the procedure and allowing the graft to be brought into the subacromial space in the definitive position, with the appropriate tension. The allografts are available from this institution's tissue bank, cryopreserved and submitted to microbiological and histopathological evaluation. Superior capsular reconstruction is a promising surgery. The technique described in the present technical note shows a viable arthroscopic alternative, with a smaller number of anchors when compared with other techniques.


Clinical Presentation of Small Intestinal Bacterial Overgrowth from Aerodigestive Tract Bacteria Versus Colonic-Type Bacteria: A Comparison Study.
Small Intestinal Bacterial Overgrowth (SIBO) is a heterogenous syndrome from excessive bacteria in the small intestine lumen. It is unknown if differences in type of bacterial overgrowth lead to differences in symptoms. Patients with suspected SIBO were recruited prospectively. Exclusion criteria were probiotics, antibiotics, or bowel prep in preceding 30 days. Clinical characteristics, risk factors, and labs were collected. Proximal jejunal aspiration via upper enteroscopy was performed. Aerodigestive tract (ADT) SIBO was defined as > 105 CFU/mL of oropharyngeal and respiratory bacteria. Colonic-type SIBO was defined as > 104 CFU/mL of distal small bowel and colon bacteria. Aims were to compare symptom profiles, clinical complications, labs, and underlying risk factors between ADT and colonic-type SIBO. We consented 166 subjects. Aspiration was not obtained in 22 and SIBO was found in 69 (49%) of 144 subjects. Daily abdominal distention trended towards more prevalent in ADT SIBO versus colonic-type SIBO (65.2% vs 39.1%, p = 0.09). Patient symptom scores were similar. Iron deficiency was more prevalent in ADT SIBO (33.3% vs 10.3%, p = 0.04). Subjects with colonic-type SIBO were more likely to have a risk factor for colonic bacteria colonization (60.9% vs 17.4%, p = 0.0006). Subjects with ADT SIBO were more likely to have a risk factor for diminished gastric acid (91.3% vs 67.4%, p = 0.02). We found differences in iron deficiency and underlying risk factors between ADT and colonic-type SIBO. However, distinct clinical profiles remained elusive. Future research is needed to develop validated symptom assessment tools and distinguish cause from correlation.


A modified Langmuir-Freundlich isotherm model for simulating pH-dependent adsorption effects.
Analytical isotherm equations such as Langmuir and Freundlich isotherms are widely used for modeling adsorption data. However, these isotherms are primarily useful for simulating data collected at a fixed pH value and cannot be easily adapted to simulate pH-dependent adsorption effects. Therefore, most adsorption studies currently use numerical surface-complexation models (SCMs), which are more complex and time consuming than traditional analytical isotherm models. In this work, we propose a new analytical isotherm model, identified as the modified Langmuir-Freundlich (MLF) isotherm, which can be used to simulate pH-dependent adsorption. The MLF isotherm uses a linear correlation between pH and affinity coefficient values. We validated the proposed MLF isotherm by predicting arsenic adsorption onto two different types of sorbents: pure goethite and goethite-coated sand. The MLF model gave good predictions for both experimental and surface complexation-model predicted datasets for these two sorbents. The proposed analytical isotherm framework can help reduce modeling complexity, model development time, and computational efforts. One of the limitations of the proposed method is that it is currently valid only for single-component systems. Furthermore, the model requires a system-specific pH. vs. affinity coefficient relation. Despite these limitations, the approach provides a promising analytical framework for simulating pH-dependent adsorption effects.


Head and neck cancer organoids as a promising tool for personalized cancer therapy: A literature review.
Chemotherapy and targeted therapy are used in treating head and neck cancers (HNCs) either alone or in combination with surgery, especially in advanced tumors but these treatments have resulted in variable outcomes in different patients. This, along with the introduction of new therapies to improve the survival of patients makes it necessary to search for models that can predict the response to treatment among different patients. Organoids, as three-dimensional culture models, have been studied more widely in non-HNCs and to a lesser extent in HNCs as tools to predict treatment outcomes. We aimed to conduct a review to validate the use of organoids as a preclinical tool for the treatment of HNCs patients. A comprehensive literature search was separately performed by both authors in PubMed and google scholar databases, using the following keywords: "organoid," "head and neck cancer," "personalized medicine," "chemotherapy," and "targeted therapy." The articles published up to September 2021 were included in this review and selected according to a quality appraisal method. Examination of HNC-derived organoids made in various studies showed that these organoids had the ability to recapitulate original tumor features, including histopathological properties, functional characteristics, and expression of molecular markers in almost all of the studies. Differential sensitivity to chemotherapy drugs similar to in vivo was observed in sensitivity testing. Epidermal growth factor receptor (EGFR) expression levels were different between organoids from different patients and EGFR expression level was found to correlate with the response to anti-EGFR targeted therapy. A similar result was reported for organoids derived from salivary adenoid cystic carcinoma. Since HNC-derived organoids seem to recapitulate characteristics of original tumors and to show differential responses to different chemotherapy and targeted therapy agents, these organoids might have the potential to be used as preclinical prediction tools for the treatment of HNC patients.


Evidence for intracellular association of the glucocorticoid receptor with the 90-kDa heat shock protein.
We have investigated the association of the glucocorticoid receptor in S49 mouse lymphoma cells with the 90-kDa heat shock protein, HSP 90. Proteins were synthetically labeled by culturing cells with [35S]methionine and immunoadsorbed to protein A-Sepharose using monoclonal antireceptor antibody (BuGR-2). HSP 90 coimmunoadsorbed with the receptor when cytosol was incubated with antireceptor antibody for 1 h in the absence of molybdate, indicating that molybdate is not required for either formation or recovery of HSP 90-receptor complexes. Molybdate stabilized HSP 90-receptor complexes during prolonged incubation in vitro and rendered the complexes resistant to dissociation by 500 mM NaCl. In pulse-chase experiments, cells were incubated with [35S]methionine for 30 min (pulse label) and then cultured with excess unlabeled methionine (chase). At different times in the chase, cytosol was prepared from cells, and labeled proteins were immunoadsorbed by antireceptor antibody. The amount of labeled receptor recovered from cytosol decreased during the chase with a half-life of about 4 h. Labeled HSP 90 coimmunoadsorbed with the receptor at 4 h into the chase but not at the beginning of the chase or at 2 h into the chase, indicating that newly synthesized HSP 90 associated with the receptor in a time-dependent manner during the chase. Labeled HSP 90 did not associate with the receptor when dexamethasone was added to cells at the beginning of the chase. These findings support the hypothesis that HSP 90 associates with the glucocorticoid receptor in intact cells rather than in cytosol and indicates that dexamethasone promotes dissociation of HSP 90-receptor complexes in vivo.


Histone H4 LRS mutations can attenuate UV mutagenesis without affecting PCNA ubiquitination or sumoylation.
UV is a significant environmental agent that damages DNA. Translesion synthesis (TLS) is a DNA damage tolerance pathway that utilizes specialized DNA polymerases to replicate through the damaged DNA, often leading to mutagenesis. In eukaryotic cells, genomic DNA is organized into chromatin that is composed of nucleosomes. To date, if and/or how TLS is regulated by a specific nucleosome feature has been undocumented. We found that mutations of multiple histone H4 residues mostly or entirely embedded in the nucleosomal LRS (loss of ribosomal DNA-silencing) domain attenuate UV mutagenesis in Saccharomyces cerevisiae. The attenuation is not caused by an alteration of ubiquitination or sumoylation of PCNA (proliferating cell nuclear antigen), the modifications well-known to regulate TLS. Also, the attenuation is not caused by decreased chromatin accessibility, or by alterations of methylation of histone H3 K79, which is at the center of the LRS surface. The attenuation may result from compromised TLS by both DNA polymerases ζ and η, in which Rad6 and Rad5 are but Rad18 is not implicated. We propose that a feature of the LRS is recognized or accessed by the TLS machineries either during/after a nucleosome is disassembled in front of a lesion-stalled replication fork, or during/before a nucleosome is reassembled behind a lesion-stalled replication fork.


A distinct asymmetrical pattern of cortical malformation: large unilateral malformation of cortical development with contralateral periventricular nodular heterotopia in three pediatric cases.
To describe a distinct asymmetrical pattern of cortical malformation with large focal malformations of cortical development (MCDs) and contralateral periventricular nodular heterotopia (PNH). We identified three patients with epilepsy and focal EEG abnormalities. Each patient underwent 1.5-Tesla magnetic resonance imaging (MRI) to obtain sagittal T1-weighted, axial fluid-attenuated inversion recovery (FLAIR), fast spin-echo (FSE) T2-weighted, and coronal fast spin-echo inversion recovery (FSEIR) T2-weighted images; coronal spoiled gradient recalled (SPGR) T1-weighted images were obtained in two cases. Patient 1, an 18-year-old right-handed man, had a 4-year history of intractable seizures. MRI revealed a right frontal subcortical heterotopia (SH) and a single left anterior PNH. Patient 2, a 10-year-old left-handed boy, had a 4-year history of epilepsy. MRI revealed a large region of SH in the left temporal, parietal, and occipital lobes and three right-sided PNH. Patient 3, a 16-month-old girl, had medically refractory infantile spasms. MRI revealed a large MCD in the left parietal lobe with contiguous underlying periventricular heterotopia as well as a small contralateral PNH. These cases together illustrate a distinct asymmetrical pattern of a large focal MCD with small contralateral PNH. The asymmetrical involvement of the two hemispheres suggests that the stage of maximal disruption of cortical development may differ between the two hemispheres. Further study into the mechanisms underlying such asymmetrical patterns of cortical malformation should enhance our understanding of cortical development as well as hemispheric lateralization.


Alleviation of side effects induced by irinotecan hydrochloride (CPT-11) in rats by intravenous infusion.
Irinotecan hydrochloride (CPT-11) is a potent topoisomerase I inhibitor and is established and used widely as an antitumor agent. However, it sometimes causes severe side effects such as myelosuppression and diarrhea. These dose-limiting toxicities prevent the adoption of CPT-11 in aggressive chemotherapy. Thus we sought to determine in a rat model whether extending the period of infusion of CPT-11 would ameliorate the adverse reactions. CPT-11 was administered intravenously (i.v.) to rats at a dose of 60 mg/kg per day for four consecutive days as a bolus injection or as 3-, 8- or 24-h infusions, and then blood cell counts and the incidence of acute and delayed-onset diarrhea were monitored. Serious acute and delayed-onset diarrhea and marked decreases in the number of neutrophils and lymphocytes were observed in the bolus injection group. These symptoms were alleviated in the infusion groups with the degree of alleviation dependent on infusion time. In the bolus injection group, mucosal impairment of the cecal epithelium including wall thickening, edema, a decrease in the number and size of crypts, and the formation of a pseudomembrane-like substance was observed, whereas these changes were less severe in the infusion groups. Areas under the plasma concentration-time curves (AUCpla) of CPT-11 and its metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), differed little among the bolus injection group, and the 3-h and 8-h infusion groups. However, the AUCpla values of CPT-11 and SN-38 were significantly decreased and increased, respectively, in the 24-h infusion group. The maximum plasma concentrations (Cmax) of CPT-11 decreased with increasing infusion time, but those of SN-38 did not. It was confirmed that the side effects of CPT-11 were alleviated by extending the infusion time. The pharmacokinetic parameters suggested that the Cmax of CPT-11 is closely related to the incidence and severity of adverse reactions such as myelosuppression and acute and delayed-onset diarrhea.


Transcriptomic analysis of cumulus cells shows altered pathways in patients with minimal and mild endometriosis.
Endometriosis is a chronic inflammatory disorder that is highly associated with infertility. This association seems to be related to oocyte impairment, mainly in the initial stages of endometriosis (minimal and mild), where no distortions or adhesions are present. Nonetheless, invasive oocyte analyses are not routinely feasible; thus, indirect assessment of oocyte quality is highly desirable, and, in this context, cumulus cells (CCs) may be more suitable targets of analysis. CCs are crucial in oocyte development and could be used as an index of oocyte quality. Therefore, this prospective case-control study aimed to shed light on the infertility mechanisms of endometriosis I/II by analyzing the CCs' mRNA transcription profile (women with endometriosis I/II, n = 9) compared to controls (women with tubal abnormalities or male factor, n = 9). The transcriptomic analyses of CCs from patients with minimal and mild endometriosis revealed 26 differentially expressed genes compared to the controls. The enrichment analysis evidenced some altered molecular processes: Cytokine-cytokine receptor interactions, Chemokine signaling, TNF signaling, NOD-like receptor signaling, NF-kappa B signaling, and inflammatory response. With the exception of CXCL12, all enriched genes were downregulated in CCs from patients with endometriosis. These findings provide a significant achievement in the field of reproductive biology, directing future studies to discover biomarkers of oocyte quality in endometriosis.


The first reported case of canine subcutaneous Cryptococcus flavescens infection.
This report describes the first documented case of subcutaneous infection due to Cryptococcus flavescens in a dog. The chief symptoms of the patient dog were abscessed lesions on the dorsal muzzle, right eyelid, and lower jaw. Biopsy specimens from the lesions on the dorsal muzzle and lower jaw showed pyogranulomatous inflammation with numerous yeast cells. The patient dog was diagnosed with a subcutaneous fungal infection and orally received 5 mg/kg itraconazole once a day for 2 months, the abscesses disappeared. After 1 month at the end of treatment, the skin lesions did not redevelop. Isolates from the biopsy specimens were identified as C. flavescens by molecular analysis as well as morphologic and biochemical examination, indicating that C. flavescens is a potential canine pathogen.


Visceral fat might impact left ventricular remodeling through changes in arterial stiffness in type 2 diabetes: A cross-sectional study.
Visceral fat (VF) influences left ventricular (LV) structure and diastolic function in type 2 diabetes (T2DM). However, there are limited data on the association among them based on different BMI levels as well as accounting for arterial stiffness. This study investigated the association of fat distribution, arterial stiffness, left ventricular (LV) structure and diastolic function in T2DM patients. This cross-sectional study comprised 905 patients. VF area (VFA) and subcutaneous fat area (SFA) were assessed by a dual bioelectrical impedance analyzer. Brachial-ankle pulse wave velocity (baPWV) was measured by a volume-plethysmographic apparatus and LV structure and diastolic function were echocardiography. Patients were divided into three groups based on BMI levels. Linear and logistic regression analysis were used to investigate the association. In multivariate linear regression, relative wall thickness (RWT) was negatively correlated with E/A in obese patients (β = -0.203, p = 0.004). LV mass/height2.7 was positively correlated with E/E' in normal weight (β = 0.232, p = 0.002) and obese patients (β = 0.232, p = 0.008). In multivariate logistic regression, baPWV was an independent determinant of LV remodeling (LVRM) in normal weight (OR = 1.001; 95% CI, 1.000, 1.002; P = 0.006), overweight (OR = 1.001; 95% CI, 1.000, 1.002; P = 0.008) and obese groups (OR = 1.003; 95% CI, 1.001, 1.004; P = 0.001), while VFA was correlated with arterial stiffness in normal weight (OR = 1.032; 95% CI, 1.017, 1.047; P < 0.001) and overweight groups (OR = 1.011; 95% CI, 1.002, 1.021; P = 0.015). VF might impact LVRM through changes in baPWV in T2DM patients, thus influencing diastolic function.


Controlled gastric emptying. II. In vitro erosion and gastric residence times of an erodible device in beagle dogs.
An erodible gastric retention device fabricated from various polymeric blends was examined in vitro for its dissolution properties and in vivo in fasting dogs for assessment of its gastric retention potential. Dissolution studies were conducted with extruded rods of polymer blends to assess their potential as candidates for the erodible component of a gastrically retained device. Based on results from dissolution studies, rods of poly(ortho ester)/polyethylene blends (POE/PE) (45% erosion at pH 1.5 and 24 hr) were used to fabricate arms for tetrahedron-shaped devices. Corners for the tetrahedral device were fabricated from Silastic 382 loaded with 15% barium sulfate for X-ray visualization. Beagle dogs were dosed with tetrahedron-shaped test devices administered in gelatin capsules and gastric retention monitored by X ray over a 24-hr period. A comparison of in vitro erosion rates and in vivo performance of various polymer blends indicated a definite trend for increased gastric retention of devices made from the more slowly eroding blends. The results indicate that the blending of erodible and nonerodible polymers is a valid approach for obtaining materials that will provide the necessary structural properties to achieve gastric retention yet lose integrity within a desired time.


Robust alternative to the righting reflex to assess arousal in rodents.
The righting reflex (RR) is frequently used to assess level of arousal and applied to animal models of a range of neurological disorders. RR produces a binary result that, when positive, is used to infer restoration of consciousness, often without further behavioral corroboration. We find that RR is an unreliable metric for arousal/recovery of consciousness. Instead, cortical activity and motor behavior that accompany RR are a non-binary, superior criterion that accurately calibrates and establishes level of arousal in rodents.


Comparison of Surgical Outcomes Between Invasive Mucinous and Non-Mucinous Lung Adenocarcinoma.
Invasive mucinous adenocarcinoma (IMA) is a rare subtype of invasive lung adenocarcinoma. However, the clinical course and prognostic outcomes following IMA resection, particularly postoperative recurrence, remain unclear. We pathologically reevaluated 1362 lung adenocarcinoma resections performed at our institution, categorizing cases into the IMA group (72 cases) and non-IMA group (1290 cases). The IMA group was further classified into pneumonia and nodular types based on preoperative computed tomography. Overall, the IMA group had lower carcinoembryonic antigen levels (3 vs 8 ng/mL; P < .01), fewer lymph node metastasis (4% vs 24%; P < .01), and more KRAS mutations (56% vs 7%; P < .01) than the non-IMA group. Although postoperative recurrence rates did not differ between both groups (32% vs 27%; P = 0.35), lung recurrence occurred more frequently in the IMA group (83% vs 17%; P < .01). Propensity score-matched pair analysis showed that the IMA group had fewer lymph node metastasis (3% vs 35%; P < .01), more KRAS mutations (56% vs 9%; P < .01), and higher intrapulmonary recurrence rate (84% vs 31%; P < .01) than the non-IMA group. The 5-year overall survival rates did not differ between both groups (74% vs 81%; P = 0.26). However, among patients with intrapulmonary recurrence, those in the IMA group had significantly worse prognosis than those in the non-IMA group (35% vs 77%; P < .01). Intrapulmonary recurrence, which induced significantly worse prognosis, was more likely to occur in the IMA than non-IMA group.


[A study on the thermal expansion characteristics of Alumina-zirconia nano-composite infiltrated ceramic].
To study the characteristics of thermal expansion of the alumina-zirconia nano-composite infiltrated ceramic. The thermal expansion coefficients of alumina-zirconia composite matrix, infiltrating glass and infiltrated ceramic were determined by various methods, respectively. The coefficients of thermal expansion of composite matrix with 10 wt%, 20 wt% and 30 wt% zirconia were 7.607, 7.690 and 8.111 microns/(m. degree C) respectively. The thermal expansion coefficients of AZ-8 and AZ-10 infiltration glass were 6.867 and 7.333 microns/(m. degree C), respectively. The thermal expansion coefficient of infiltrated ceramic was 8.413 microns/(m. degree C). The thermal expansion coefficients of the glass and composite matrix matched well. The thermal expansion coefficients of the alumina-zirconia nano-composite infiltrated ceramic and several common veneering porcelains matched well, too.


[Deviation in cortisol metabolism induced by rifampicin. Therapeutic consequences in adrenal failure (author's transl)].
Deviation of cortisol metabolism in favour of its 6 beta-hydroxylated derivative was demonstrated in two patients with adrenal failure receiving substitution corticosteroid therapy and rifampicin. The existence of a frank increase in the metabolic clearance antipyrin was in favour of an hepatic enzyme induction. After rifampicin treatment was stopped, the 24 hour urinary excretion of 6 beta-OH-F returned to normal, demonstrating the responsability of the drug. This enzyme induction results in a need to increase the dose of hydrocortisone substitution therapy in patients with Addison's disease treated with rifampicin.


The life history of the toxic marine dinoflagellate Protoceratium reticulatum (Gonyaulacales) in culture.
Asexual and sexual life cycle events were studied in cultures of the toxic marine dinoflagellate Protoceratium reticulatum. Asexual division by desmoschisis was characterized morphologically and changes in DNA content were analyzed by flow cytometry. The results indicated that haploid cells with a C DNA content occurred only during the light period whereas a shift from a C to a 2C DNA content (indicative of S phase) took place only during darkness. The sexual life cycle was documented by examining the mating type as well as the morphology of the sexual stages and nuclei. Gamete fusion resulted in a planozygote with two longitudinal flagella, but longitudinally biflagellated cells arising from planozygote division were also observed, so one of the daughter cells retained two longitudinal flagella while the other daughter cell lacked them. Presumed planozygotes (identified by their longitudinally biflagellated form) followed two life-cycle routes: division and encystment (resting cyst formation). Both the division of longitudinally biflagellated cells and resting cyst formation are morphologically described herein. Resting cyst formation through sexual reproduction was observed in 6.1% of crosses and followed a complex heterothallic pattern. Clonal strains underwent sexuality (homothallism for planozygote formation and division) but without the production of resting cysts. Ornamental processes of resting cysts formed from the cyst wall under an outer balloon-shaped membrane and were fully developed in <1h. Obligatory dormancy period was of ∼4 months. Excystment resulted in a large, rounded, pigmented, longitudinally biflagellated but motionless, thecate germling that divided by desmoschisis. Like the planozygote, the first division of the germling yielded one longitudinally biflagellated daughter cell and another without longitudinal flagella. The longitudinal biflagellation state of both sexual stages and of the first division products of these cells is discussed.


Semantic interoperability: ontological unpacking of a viral conceptual model.
Genomics and virology are unquestionably important, but complex, domains being investigated by a large number of scientists. The need to facilitate and support work within these domains requires sharing of databases, although it is often difficult to do so because of the different ways in which data is represented across the databases. To foster semantic interoperability, models are needed that provide a deep understanding and interpretation of the concepts in a domain, so that the data can be consistently interpreted among researchers. In this research, we propose the use of conceptual models to support semantic interoperability among databases and assess their ontological clarity to support their effective use. This modeling effort is illustrated by its application to the Viral Conceptual Model (VCM) that captures and represents the sequencing of viruses, inspired by the need to understand the genomic aspects of the virus responsible for COVID-19. For achieving semantic clarity on the VCM, we leverage the "ontological unpacking" method, a process of ontological analysis that reveals the ontological foundation of the information that is represented in a conceptual model. This is accomplished by applying the stereotypes of the OntoUML ontology-driven conceptual modeling language.As a result, we propose a new OntoVCM, an ontologically grounded model, based on the initial VCM, but with guaranteed interoperability among the data sources that employ it. We propose and illustrate how the unpacking of the Viral Conceptual Model resolves several issues related to semantic interoperability, the importance of which is recognized by the "I" in FAIR principles. The research addresses conceptual uncertainty within the domain of SARS-CoV-2 data and knowledge.The method employed provides the basis for further analyses of complex models currently used in life science applications, but lacking ontological grounding, subsequently hindering the interoperability needed for scientists to progress their research.


Excess body weight is not independently associated with outcome in mechanically ventilated patients with acute lung injury.
Despite an epidemic of obesity among adults, the effect of excess body weight on outcome from critical illness is not well studied. To examine the association between excess body weight and outcome in mechanically ventilated patients with acute lung injury. Secondary analysis of participants in trials of therapy for acute lung injury. 10 U.S. medical centers that participate in the National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network. 902 mechanically ventilated patients who were enrolled in randomized, controlled trials of therapy for acute lung injury. Assignment to higher (12 mL/kg of predicted weight) or lower (6 mL/kg of predicted weight) tidal volume ventilation strategies with specified weaning protocols. Some patients also received ketoconazole, lisofylline, or placebo by factorial design. Mortality rate, rate of unassisted ventilation by day 28, and number of ventilator-free days. Indirect causes of lung injury, including trauma, were more common in obese patients. Overweight and obese patients had higher peak and plateau airway pressures before enrollment because of higher set tidal volumes. After risk adjustment, excess body weight was not associated with death, achievement of unassisted ventilation, or number of ventilator-free days. This lack of effect persisted with categorical or continuous measures of body mass index (BMI). We found no significant interaction between ventilator protocol assignment and BMI category. After risk adjustment, overweight and obese patients with acute lung injury have outcomes similar to those of patients with normal BMI. The lack of interaction between ventilator protocol assignment and BMI suggests that patients with normal, overweight, or obese BMI benefit from lower tidal volume ventilation for acute lung injury.


[Surgical therapy of gynecomastia].
Nowadays surgical intervention is an essential part of the treatment of idiopathic gynecomastia. Choosing the right method is crucial and is based on the current status in the clinical and histological evaluation. Before finalizing the process of choosing a specific method a prior interdisciplinary evaluation of the patient is necessary to ascertain clear indications for a surgical intervention. Liposuction is one of the methods which have become popular in recent years. The advantages are the possible combination with traditional techniques, such as subcutaneous mastectomy or periareolar mastopexy. The main indication is for gynecomastia stage IIa/b and is justifiable due to the reduction in surgical complications and scarring. Furthermore this technique provides an excellent aesthetical outcome for the patient. A total of 162 patients suffering from gynecomastia stages I-III (according to Simon) were surgically treated between 2000 and 2010 and these cases were retrospectively evaluated. The results showed a decline in the use of a T-shaped incision in combination with subcutaneous mastectomy with periareolar tightening compared to an increase in the use of subcutaneous mastectomy in combination with liposuction. The excised tissue should always be sent for histological examination to make sure no malignant cells were present.


Neonatal risk factors in preterm infants.
This paper highlights the research literature on neonatal risk factors and explores the paradox that these factors present. Clinical and retrospective studies indicate that children who have developmental problems have had birth complications. On the other hand, birth complications do not predict developmental problems. Data from a longitudinal study of preterm infants are presented. A group of 59 preterm infants from English Speaking homes was assessed repeatedly from birth to age 5. A significant percentage of the children performed within the normal range or above, at each assessment period. Obstetrical and postnatal complications were not significantly related to developmental performance at any assessment period yet sickness was not to be dismissed as a risk factor. At age five, all of the children who performed poorly had experienced complications in the neonatal period. Responsive caregiving appeared to be an important factor in modifying and supporting cognitive development.


Comparison of the Dermatology Life Quality Index and the Children's Dermatology Life Quality Index in assessment of quality of life in patients with psoriasis aged 16-17 years.
Dermatology Life Quality Index (DLQI) and Children's Dermatology Life Quality Index (CDLQI) are widely used to assess quality of life (QoL) in adults (≥ 16 years) and children (4-16 years) with psoriasis. In the age group 16-17 years, it is not known whether DLQI and CDLQI reflect QoL impairment in the same way. To compare DLQI and CDLQI scores in patients with psoriasis aged 16-17 years. Patients with psoriasis aged 16-17 years were asked to complete both the DLQI and CDLQI. Fifty-six patients were included. There was a high correlation between DLQI and CDLQI scores (r = 0·90, P < 0·001). The mean DLQI score (5·41 ± 5·20) was lower than the mean CDLQI (6·61 ± 5·74) (P < 0·001). The major part of this difference (∆0·61) was caused by the low score regarding sexual difficulties in the DLQI (0·11 ± 0·49) and the high score concerning sleep in the CDLQI (0·71 ± 0·93). In addition, the question related to sports scored 0·34 in the DLQI but 0·86 in the CDLQI (∆0·52). The question related to work/study in the DLQI scored lower than the question on school/holiday in the CDLQI (∆0·41). In patients with psoriasis aged 16-17 years, DLQI and CDLQI scores closely correlate, but the mean DLQI score was lower than the mean CDLQI score. This was caused primarily by differences in the answers to questions regarding sexual difficulties and sleep. As the QoL impacts experienced by people aged 16-17 may differ from those experienced by children or adults, QoL measures designed for use in this age range may have advantages over both child- and adult-specific measures.


LncRNA as potential biomarker and therapeutic target in glioma.
Glioma is the most frequent type of malignant tumor in the central nervous system, accounting for about 80% of primary malignant brain tumors, usually with a poor prognosis. A number of studies have been conducted on the molecular abnormalities in glioma to further understand its pathogenesis, and it has been found that lncRNAs (long non-coding RNA) play a key role in angiogenesis, tumor growth, infiltration and metastasis of glioma. Since specific lncRNAs have an aberrant expression in brain tissue, cerebrospinal fluid as well as peripheral circulation of glioma patients, they are considered to be potential biomarkers. This review focuses on the biological characteristics of lncRNA and its value as a biomarker for glioma diagnosis and prognosis. Moreover, in view of the role of lncRNAs in glioma proliferation and chemoradiotherapy resistance, we discussed the feasibility for lncRNAs as therapeutic targets. Finally, the persisting deficiencies and future prospects of using lncRNAs as clinical biomarkers and therapeutic targets were concluded.


Identification of the key excreted molecule by Lactobacillus fermentum related to host iron absorption.
We have taken a vital step towards understanding why probiotic bacteria increase iron absorption in the gastrointestinal tract. We show here that Lactobacillus fermentum, one of the main probiotics of the microbiota, exhibits an extraordinary ferric-reducing activity. This activity is predominantly due to an excreted molecule: p-hydroxyphenyllactic acid (HPLA). Reduction of Fe(III) to Fe(II) is essential for iron absorption in the gastrointestinal tract. By reducing Fe(III), HPLA boosts Fe(II) absorption through the DMT1 channels of enterocytes. An in vitro experiment tested and confirmed this hypothesis. This discovery opens new avenues for the treatment of iron deficiency in humans, one of the most common and widespread nutritional disorders in the world.


Thermodynamics of the interaction of Pd(dmen)(H₂O)₂²⁺ with bio-relevant ligands with reference to the deactivation of metal-based drug by thiol ligands.
Pd(dmen)Cl(2) complex was synthesized and characterized, where dmen=N,N-dimethylethylenediamine. Stoichiometry and stability constants of the complexes formed between [Pd(dmen)(H(2)O)(2)](2+) and various biologically relevant ligands such as amino acids, peptides and dicarboxylic acids are investigated at 25 °C and at constant 0.1M ionic strength. The concentration distribution diagrams of the various species formed are evaluated. The equilibrium constants for the displacement of coordinated ligands as inosine, glycine or methionine by cysteine are calculated. The results are expected to contribute to the chemistry of tumour therapy.


Gas-particle partition and size-segregated distribution of flame retardants in indoor and outdoor air: Reevaluation on the role of fine particles in human exposure.
In this study, we investigated the distribution of brominated and organophosphate flame retardants (BFRs and OPFRs) in the paired gaseous and nine size-segregated particulate samples collected from 8 typical indoor compartments and monthly outdoor in Xinxiang, China, respectively. For the indoor environments, total concentrations of FRs (Σ19FRs) in bulk air ranged from 3.9 ng/m3 to 37.5 ng/m3, with that in children recreation center (37.5 ng/m3) and furniture store (28.7 ng/m3) showing highest levels. In the outdoor air, Σ19FRs ranged from 3.1 ng/m3 to 13.6 ng/m3 among the 12 months, with that from late spring and summer being the highest. OPFRs had higher concentration than BFRs, with the total concentration of OPFRs accounting for 77%-99% of ∑19FRs. TCIPP (tris(chloroiso-propyl) phosphate), TCEP (tris(2-chloroethyl) phosphate), TEP (triethyl phosphate) and DBDPE (decabromodiphenyl ethane), BDE-209 (decabromodiphenyl ether) were the predominant analogs. Specifically, BFRs tended to enrich in gas phase indoors and coarse particles (aerodynamic diameters >3.3 μm) outdoors, but OPFRs mainly distributed in coarse particles both indoors and outdoors. The size distribution patterns varied among FRs, with the higher volatile FRs (e.g., TCEP, TCIPP) distributed more uniformly across particulate size. Although the distribution patterns of FRs in air were driven by multiple factors, organic carbon and element carbon in particulate matter had an influence to a certain extent. Health risks from exposure to FRs were characterized via the hazard quotient approaches. The total noncarcinogenic risks of ∑16FRs from inhalation were higher than that from air to skin transport, and the risks resulted from coarse particle-bound ∑16FRs (>3.3 μm) and gas phase were both significantly higher than that from fine fraction (<3.3 μm) in all scenarios, implying that FRs in coarse particles should not be underestimated.