Synthesis and Identification of Key Biosynthetic Intermediates for the Formation of the Tricyclic Skeleton of Saxitoxin.
Saxitoxin (STX) and its analogues are potent voltage-gated sodium channel blockers biosynthesized by freshwater cyanobacteria and marine dinoflagellates. We previously identified genetically predicted biosynthetic intermediates of STX at early stages, Int-A' and Int-C'2, in these microorganisms. However, the mechanism to form the tricyclic skeleton of STX was unknown. To solve this problem, we screened for unidentified intermediates by analyzing the results from previous incorporation experiments with 15 N-labeled Int-C'2. The presence of monohydroxy-Int-C'2 and possibly Int-E' was suggested, and 11-hydroxy-Int-C'2 and Int-E' were identified from synthesized standards and LC-MS. Furthermore, we observed that the hydroxy group at C11 of 11-hydroxy-Int-C'2 was slowly replaced by CD3 O in CD3 OD. Based on this characteristic reactivity, we propose a possible mechanism to form the tricyclic skeleton of STX via a bicyclic intermediate from 11-hydroxy-Int-C'2.


The addition of O2 to the CO2 does not prevent the systemic effects of the CO2 pneumoperitoneum in a rabbit model.
CO2 pneumoperitoneum used in endoscopic surgery induces systemic effects by CO2 absorption. It was claimed that a reduction in CO2 pneumoperitoneum-induced metabolic hypoxemia was achieved by the addition of small amounts of O2 to the CO2 in a rabbit ventilated model. We reevaluated the effects of the addition of O2 to the CO2 pneumoperitoneum upon CO2 absorption in a rabbit model. The effects of a pneumoperitoneum using 100% CO2, 90% CO2 + 10% O2, 95% CO2 + 5% O2, or 100% O2 on arterial blood gases, acid base and O2 homeostasis were evaluated in nonintubated rabbits. A pneumoperitoneum pressure of 10 cm H2O (approximately 7.35 mm Hg) was used. CO2 pneumoperitoneum of 120 minutes affected blood gases and acid base homeostasis. Whereas partial pressure of CO2 and HCO3 increased (P < 0.001) during pneumoperitoneum, pH and partial pressure of O2 decreased (P < 0.001). Similar results were obtained in O2-CO2 pneumoperitoneum (P > 0.05). CO2 pneumoperitoneum profoundly affected blood gases and acid base homeostasis, resulting in metabolic hypoxemia. The addition of O2 to the CO2 did not prevent the systemic effects of CO2 pneumoperitoneum in nonintubated animals.


Genome analysis of Phytophthora cactorum strains associated with crown- and leather-rot in strawberry.
Phytophthora cactorum has two distinct pathotypes that cause crown rot and leather rot in strawberry (Fragaria × ananassa). Strains of the crown rot pathotype can infect both the rhizome (crown) and fruit tissues, while strains of the leather rot pathotype can only infect the fruits of strawberry. The genome of a highly virulent crown rot strain, a low virulent crown rot strain, and three leather rot strains were sequenced using PacBio high fidelity (HiFi) long read sequencing. The reads were de novo assembled to 66.4-67.6 megabases genomes in 178-204 contigs, with N50 values ranging from 892 to 1,036 kilobases. The total number of predicted complete genes in the five P. cactorum genomes ranged from 17,286 to 17,398. Orthology analysis identified a core secretome of 8,238 genes. Comparative genomic analysis revealed differences in the composition of potential virulence effectors, such as putative RxLR and Crinklers, between the crown rot and the leather rot pathotypes. Insertions, deletions, and amino acid substitutions were detected in genes encoding putative elicitors such as beta elicitin and cellulose-binding domain proteins from the leather rot strains compared to the highly virulent crown rot strain, suggesting a potential mechanism for the crown rot strain to escape host recognition during compatible interaction with strawberry. The results presented here highlight several effectors that may facilitate the tissue-specific colonization of P. cactorum in strawberry.


On the use of the quasi-Gaussian entropy theory in the study of simulated dilute solutions.
In a recent paper [M. D'Alessandro, M. D'Abramo, G. Brancato, A. Di Nola, and A. Amadei, J. Phys. Chem. B 106, 11843 (2002)] we showed how to combine molecular dynamics simulations with the quasi-Gaussian entropy theory, in order to model the statistical mechanics and thermodynamics of ionic (water) solutions. In this paper we extend the method to treat nonspherical solutes, describe more thoroughly its theoretical basis and apply it to a set of more complex solute molecules in water (i.e., water, methane, ethane, methanol, and ethanol). Results show that this approach can really provide an excellent theoretical description of solute-solvent systems over a wide range of temperatures.


Translational isomerizations in [2]catenanes with unsymmetrically substituted resorcinol-based tethers.
The translational isomerizations of nine [2]catenanes (2-10) containing an electron-rich dibenzo-34-crown-10 ether (BPP34C10) interlocked with rings containing an unsymmetric 4-substituted (chloro, ethyl, or hexyl) resorcinol-based tether linking two electron-deficient dipyridyl groups have been studied by variable temperature (VT) 1H NMR spectroscopy. The second symmetric tether between the dipyridyl groups was a large 5-(4-tert-butylphenyl)-1,3-xylyl (catenanes 2-4), a narrower 1,3-xylyl (catenanes 5-7), or a narrow 1,4-xylyl (catenanes 8-10) group. The presence of the unsymmetrically placed substituent on the resorcinol tether substantially affected the binding energy of the BPP34C10 ring when pi-stacked over either of the dipyridyl groups; the equilibrium constant between the bistable states was found to range from 1.5 to 3.5. The origin of these energy differences is postulated to stem from an unsymmetric twisting of the resorcinol tether to minimize interaction between the 4-substituent and the ethoxy group at the 3-position. The activation barriers for passage over the 4-substituted resorcinol-based tether were 12.5, 13, and 15 kcal/mol for the chloro, ethyl, and hexyl substituents, respectively.


Care and cultural context of Lebanese Muslim immigrants: using Leininger's theory.
The purpose of this ethnonursing study was to describe and analyze the meanings and experiences of care for Lebanese Muslims as influenced by cultural context in selected natural and community settings. Leininger's theory of Cultural Care Diversity and Universality served as the conceptualizing frame-work for the study. Research questions focused on discovering the meanings and experiences of care as influenced by world view, social structure, and cultural context in the hospital, clinic, and home. Ethno-nursing research methods were used with key and general informants in an urban US community. The majority of informants were new immigrants living less than 10 years in the US. Universal themes of care that were similar in the three contexts reflected care as a religious obligation in Islam, care as equal but different gender role responsibilities, and care as individual and collective meanings of honor. This article also presents findings related to gender role responsibilities. Nursing decisions and actions using Leininger's three modes were identified to achieve culturally congruent nursing care.


Misdiagnosis of HIV treatment failure based on clinical and immunological criteria in Eastern and Central Kenya.
Routine laboratory monitoring is part of the basic care package offered to people living with the Human Immunodeficiency Virus (PLHIV). This paper aims to identify the proportion of PLHIVs with clinical and immunological failure who are virologically suppressed and risk being misclassified as treatment failures. A retrospective analysis of patient viral load data collected between January 2013 and June 2014 was conducted. Of the patients classified as experiencing either clinical or immunological failure, we evaluated the proportion of true (virological) failure, and estimated the sensitivity and specificity of the immunological and clinical criteria in diagnosing true treatment failure. Of the 27,418 PLHIVs aged 2-80 years on ART in the study period, 6.8% (n = 1859) were suspected of treatment failure and their viral loads analysed. 40% (n = 737) demonstrated viral suppression (VL < 1000 copies/ml). The median viral load (VL) was 3317 copies/ml (IQR 0-47,547). Among the 799 (2.9%) PLHIVs on ART classified as having clinical failure, 41.1% (n = 328) of them had confirmed viral suppression. Of the 463 (1.7%) classified as having immunological failure, 36.9% (n = 171) had confirmed viral suppression. The sensitivity of the clinical criteria in diagnosing true failure was 61% (CI 58%-65%) while that of the immunological criteria 38% (CI 35%-42%). The specificity of the clinical criteria was 34% (CI 30%-39%) while that of the immunological criteria 66% (61%-70%). Age below 20 years was associated with a high viral load (p < .001). Sex and ART regimen were not associated with the viral load. Clinical and immunological criteria alone are not sufficient to identify true treatment failure. There is need for accurate treatment failure diagnosis through viral load testing to avoid incorrect early or delayed switching of patients to second-line regimens. This study recommends increased viral load testing in line with the Kenya's ART guidelines.


Dual-Recognition Förster Resonance Energy Transfer Based Platform for One-Step Sensitive Detection of Pathogenic Bacteria Using Fluorescent Vancomycin-Gold Nanoclusters and Aptamer-Gold Nanoparticles.
The effective monitoring, identification, and quantification of pathogenic bacteria is essential for addressing serious public health issues. In this study, we present a universal and facile one-step strategy for sensitive and selective detection of pathogenic bacteria using a dual-molecular affinity-based Förster (fluorescence) resonance energy transfer (FRET) platform based on the recognition of bacterial cell walls by antibiotic and aptamer molecules, respectively. As a proof of concept, Vancomycin (Van) and a nucleic acid aptamer were employed in a model dual-recognition scheme for detecting Staphylococcus aureus (Staph. aureus). Within 30 min, by using Van-functionalized gold nanoclusters and aptamer-modified gold nanoparticles as the energy donor and acceptor, respectively, the FRET signal shows a linear variation with the concentration of Staph. aureus in the range from 20 to 108 cfu/mL with a detection limit of 10 cfu/mL. Other nontarget bacteria showed negative results, demonstrating the good specificity of the approach. When employed to assay Staph. aureus in real samples, the dual-recognition FRET strategy showed recoveries from 99.00% to the 109.75% with relative standard derivations (RSDs) less than 4%. This establishes a universal detection platform for sensitive, specific, and simple pathogenic bacteria detection, which could have great impact in the fields of food/public safety monitoring and infectious disease diagnosis.


Has prolactin an intermedin-like activity on the integument of the Axolotl?
Skin explants of the neotenic form of Ambystoma tigrinum (Axolotl) have been kept in culture during several days. When alpha-MSH or prolactin are added to the medium, a dispersion of melanin in melanosomes is observed. The reaction is reversible in the case of prolactin when the explants are transferred in the medium without hormones. Furthermore with prolactin, expansion of melanin in dermal melanophores is a more permanent and highly reproducible phenomenon, compared with the action of alpha-MSH in the same conditions. The type of action of prolactin could be different of the one of alpha-MSH.


Correlation between localization of supratentorial glioma to the precentral gyrus and difficulty in identification of the motor area during awake craniotomy.
Identification of the motor area during awake craniotomy is crucial for preservation of motor function when resecting gliomas located within or close to the motor area or the pyramidal tract. Nevertheless, sometimes the surgeon cannot identify the motor area during awake craniotomy. However, the factors that influence failure to identify the motor area have not been elucidated. The aim of this study was to assess whether tumor localization was correlated with a negative cortical response in motor mapping during awake craniotomy in patients with gliomas located within or close to the motor area or pyramidal tract. Between April 2000 and May 2019 at Tokyo Women's Medical University, awake craniotomy was performed to preserve motor function in 137 patients with supratentorial glioma. Ninety-one of these patients underwent intraoperative cortical motor mapping for a primary glioma located within or close to the motor area or pyramidal tract and were enrolled in the study. MRI was used to evaluate whether or not the tumors were localized to or involved the precentral gyrus. The authors performed motor functional mapping with electrical stimulation during awake craniotomy and evaluated the correlation between identification of the motor area and various clinical characteristics, including localization to the precentral gyrus. Thirty-four of the 91 patients had tumors that were localized to the precentral gyrus. The mean extent of resection was 89.4%. Univariate analyses revealed that identification of the motor area correlated significantly with age and localization to the precentral gyrus. Multivariate analyses showed that older age (≥ 45 years), larger tumor volume (> 35.5 cm3), and localization to the precentral gyrus were significantly correlated with failure to identify the motor area (p = 0.0021, 0.0484, and 0.0015, respectively). Localization to the precentral gyrus showed the highest odds ratio (14.135) of all regressors. Identification of the motor area can be difficult when a supratentorial glioma is localized to the precentral gyrus. The authors' findings are important when performing awake craniotomy for glioma located within or close to the motor area or the pyramidal tract. A combination of transcortical motor evoked potential monitoring and awake craniotomy including subcortical motor mapping may be needed for removal of gliomas showing negative responses in the motor area to preserve the motor-related subcortical fibers.


Connections of the parabrachial nucleus with the nucleus of the solitary tract and the medullary reticular formation in the rat.
We examined the subnuclear organization of projections to the parabrachial nucleus (PB) from the nucleus of the solitary tract (NTS), area postrema, and medullary reticular formation in the rat by using the anterograde and retrograde transport of wheat germ agglutinin-horseradish peroxidase conjugate and anterograde tracing with Phaseolus vulgaris-leucoagglutinin. Different functional regions of the NTS/area postrema complex and medullary reticular formation were found to innervate largely nonoverlapping zones in the PB. The general visceral part of the NTS, including the medial, parvicellular, intermediate, and commissural NTS subnuclei and the core of the area postrema, projects to restricted terminal zones in the inner portion of the external lateral PB, the central and dorsal lateral PB subnuclei, and the "waist" area. The dorsomedial NTS subnucleus and the rim of the area postrema specifically innervate the outer portion of the external lateral PB subnucleus. In addition, the medial NTS innervates the caudal lateral part of the external medial PB subnucleus. The respiratory part of the NTS, comprising the ventrolateral, intermediate, and caudal commissural subnuclei, is reciprocally connected with the Kölliker-Fuse nucleus, and with the far lateral parts of the dorsal and central lateral PB subnuclei. There is also a patchy projection to the caudal lateral part of the external medial PB subnucleus from the ventrolateral NTS. The rostral, gustatory part of the NTS projects mainly to the caudal medial parts of the PB complex, including the "waist" area, as well as more rostrally to parts of the medial, external medial, ventral, and central lateral PB subnuclei. The connections of different portions of the medullary reticular formation with the PB complex reflect the same patterns of organization, but are reciprocal. The periambiguus region is reciprocally connected with the same PB subnuclei as the ventrolateral NTS; the rostral ventrolateral reticular nucleus with the same PB subnuclei as both the ventrolateral (respiratory) and medial (general visceral) NTS; and the parvicellular reticular area, adjacent to the rostral NTS, with parts of the central and ventral lateral and the medial PB subnuclei that also receive rostral (gustatory) NTS input. In addition, the rostral ventrolateral reticular nucleus and the parvicellular reticular formation have more extensive connections with parts of the rostral PB and the subjacent reticular formation that receive little if any NTS input. The PB contains a series of topographically complex terminal domains reflecting the functional organization of its afferent sources in the NTS and medullary reticular formation.


Targeted Degradation of Androgen Receptor for the Potential Treatment of Prostate Cancer.
Prostate cancer (PCa) is the fourth most commonly diagnosed cancer in the world. Antiandrogens treatments have eventually mostly induced resistant mutations in patients, and when higher dosages are administered, they might cause adverse effects, such as fatigue, back pain, and constipation. The present Patent Highlight provides PROTACs that degrade or inhibit the androgen receptor at low concentrations in a subject in need of treatment.


Utility of Y-STR haplotype and mtDNA sequence in personal identification of human remains.
The utility of Y-STR haplotype and mtDNA sequence in personal identification from human remains is demonstrated. In five cases, severely damaged human remains were identified by Y-chromosomal short tandem repeat (STR) (Y-STR) haplotyping and mitochondrial DNA (mtDNA) sequencing. DNA was extracted from highly adipoceratous tissues using the phenol-chloroform method and polymerase chain reaction amplified for Y-STR haplotyping and sequencing of two hypervariable regions, HV1 and HV2, of the mtDNA. The authors also profiled the Y-STR haplotype and mtDNA sequence of a blood sample that was obtained from the presumptive brother of the decedent. Y-STR haplotyping and mtDNA sequencing results were compared with one another and with the Anderson sequence. It was concluded from these data that the lower part of the body (Case 1), the human head (Case 2), the upper part of the body (Case 3), and the right arm (Case 4) were from the same individual, whereas another lower part of a body (Case 5) was from a relative of the presumptive brother. A novel descriptive way of a statistical characteristic, gene or haplotype diversity, is shown.


[Disseminated actinomycosis].
We report the case of a patient suffering from disseminated actinomycosis. A fifty-two year old man, who was both a heavy smoker and an alcoholic, was admitted to hospital with confusion associated with a pseudo-tumoral right upper lobe pneumonia. Brain computed tomography was normal on the day of admission but when repeated fifteen days later four lesions were seen with appearances suspicious of metastatic malignant disease. The isolation of Actinomyces odontolyticus in the bronchoalveolar lavage culture and the absence of evidence for neoplastic disease despite extensive investigation led to a diagnosis of disseminated actinomycosis with pulmonary and cerebral involvement. The patient's clinical condition improved with antibiotic therapy. The disseminated form of this infection as well as presentation with multifocal brain abscesses is rare. The diagnosis of actinomycosis is problematic because it is an uncommon infection and microbiological identification is often difficult and delayed. It should be considered when clinical presentation suggests malignant disease but there is no histological confirmation.


High-dose radiotherapy plus prolonged hormone therapy in CT2-3 prostatic carcinoma: is it useful?
Clinical studies published in the last decade have shown the possible improvement in prognosis of patients with prostatic carcinoma undergoing radiation therapy with dose escalation or in combination with hormone therapy. However, in studies on hormone therapy, moderate doses of radiation therapy have been used, whereas in studies with high-dose radiotherapy, hormone therapy usually was not administered. Therefore, it is not clear whether the concomitant use of high doses and prolonged hormone therapy could determine an additional beneficial effect. The aim of the present study was therefore to evaluate the relative prognostic role of different dose levels (< 70 versus > or = 70 Gy) of external beam radiotherapy and of different hormone therapies (neoadjuvant only versus neoadjuvant + adjuvant). A total of 426 patients (median age, 71 yrs; range, 51-87 yrs) underwent external beam radiotherapy (70 Gy median dose to prostate volume +/- 45 Gy to pelvic lymph nodes) and neoadjuvant hormone therapy (bicalutamide for 30 days; goserelin, 3.6 mg every 28 days starting two months before radiotherapy and for its entire duration). Dose to the prostate was < 70 Gy in 44.8% of patients and > or = 70 Gy in 55.2%. A total of 244 patients received adjuvant hormonal therapy. The distribution according to the clinical stage was 48.1% T2 and 51.9% T3. The distribution according to the Gleason score was 14.3% grades 2-4, 66.7% grades 5-7 and 19.0% grades 8-10. The distribution according to pretreatment prostate-specific antigen levels (in ng/mL) was 7.0% for 0-4, 29.3% for 4-10, 30.3% for 10-20, and 33.3% for > 20. With a median follow-up of 35 months (range, 1-151), 81 patients (19.0%) showed biochemical recurrence, 17 patients (4.0%) showed local disease progression, and 12 patients (2.8%) showed distant metastases. Overall, 23 patients (5.4%) showed disease progression. Four patients (0.9%) died. At the time of this writing, no patient has died from prostatic carcinoma. At univariate analysis, the radiation dose delivered to the tumor and the administration of adjuvant hormone therapy were shown to be significantly correlated with biochemical disease-free survival. At multivariate analysis, the single parameter significantly correlated with biochemical disease-free survival was the radiation dose delivered to the tumor. In the subset of patients not treated with adjuvant hormone therapy, there was a significant correlation between radiation dose and biochemical disease-free survival at univariate and multivariate analysis. A similar correlation between adjuvant hormone therapy and biochemical disease-free survival was observed in the subset of stage cT3 patients at univariate and multivariate analysis. In patients undergoing combined treatment without adjuvant hormone therapy, a significant correlation was observed between clinical stage and biochemical disease-free survival, at univariate and at multivariate analysis. The results of the study confirmed the positive impact of radiotherapy doses > 70 Gy and of adjuvant hormone therapy in patients with locally advanced prostatic carcinoma. Owing to the lack of evidence of a correlation between radiation dose and biochemical outcome in patients undergoing prolonged hormone therapy, the role of further dose escalation in patients undergoing combined hormone and radiation therapy is still unclear.


Measurement of protein charge and ion binding using capillary electrophoresis.
A new technique is described for the rapid and accurate measurement of electrophoretic mobilities of proteins in different solution environments using capillary electrophoresis. Data were obtained at different pH using surface-modified capillaries to reduce nonspecific protein adsorption and using hydrodynamic mobilization to improve reproducibility and overall accuracy. The net protein charge and extent of anion binding were evaluated from the mobility data obtained in different pH and ionic environments for bovine serum albumin. The results were in good agreement with titration data obtained using ion-selective electrodes and mobility data obtained using free solution electrophoresis. The method requires extremely small amounts of protein (picogram quantities and nanoliter volumes) and is easily automated, making it very suitable for protein characterization and for initial screening of possible separation techniques.


Candida glabrata infection following total hip arthroplasty: A case report.
Candida glabrata infection following total hip arthroplasty is rare and, due to the insufficiency of standardized clinical and evidence-based guidelines, there is no appropriate therapeutic schedule. The present study reports the case of a 44-year-old patient with Candida glabrata infection following a total hip arthroplasty. The patient was successfully treated by administration of intravenous and oral voriconazole without removal of the prosthesis. This case illustrates the significance of postoperative follow-up, clinician experience and the choice of the correct antifungal agent. In this case, we found in the early stage of Candida glabrata infection, we were able to control the infection without surgery through thorough irrigation. This reduces patient suffering and economic burden.


Ethical considerations in medical genetics--the prenatal diagnosis of hemophilia B.
A couple is presented who underwent prenatal counseling and amniocentesis for sex determination because the wife was an obligate carrier of hemophilia B. Although the fetus was determined to be male, the parents elected not to have further testing to determine if he had hemophilia or not. The difficulties in the in utero diagnosis of hemophilia B are presented and discussed. In addition, the moral reasoning and decision-making process that this couple went through regarding the decision not to have further fetal testing and to continue the pregnancy is presented and analyzed. These moral decisions appear to be based on family and personal ties, and bonding to the fetus after perception of fetal movement. They combine considerations of the duties and rights involved in such situations, and attend to the anticipated consequences as well.


Cytochrome P450 1A2 is a hepatic autoantigen in autoimmune polyglandular syndrome type 1.
Autoantibodies directed against proteins of the adrenal cortex and the liver were studied in 88 subjects of Sardinian descent, namely six patients with autoimmune polyendocrine syndrome type 1 (APS1), 22 relatives of APS1 patients, 40 controls with other autoimmune diseases, and 20 healthy controls. Indirect immunofluorescence, using tissue sections of the adrenal cortex, revealed a cytoplasmatic staining pattern in 4 of 6 patients with APS1. Western blotting with adrenal mitochondria identified autoantigens of 54 kDa and 57 kDa, Western blotting with placental mitochondria revealed a 54-kDa autoantigen. The 54-kDa protein was recognized by 4 of 6 patients with APS1 both in placental and adrenal tissue, whereas the 57-kDa protein was detected only by one serum. Using recombinant preparations of cytochrome P450 proteins, the autoantigens were identified as P450 scc and P450 c17. One of six APS1 patients suffered from chronic hepatitis. In this patient, immunofluorescence revealed a centrolobular liver and a proximal renal tubule staining pattern. Western blots using microsomal preparations of human liver revealed a protein band of 52 kDa. The autoantigen was identified as cytochrome P450 1A2 by use of recombinant protein preparations. P450 1A2 represents the first hepatic autoantigen reported in APS1. P450 1A2 usually is not detected by sera of patients with isolated autoimmune liver disease and might be a hepatic marker autoantigen for patients with APS1.


Antibody and radionuclide characteristics and the enhancement of the effectiveness of radioimmunotherapy by selective dose delivery to radiosensitive areas of tumour.
Estimating the absorbed dose to tumour relative to normal tissues has often been used in the assessment of the therapeutic efficacy of radiolabelled antibodies for radioimmunotherapy. Typically, the calculations assume a uniform dose deposition and response throughout the tumour. However, the heterogeneity of the dose delivery and response within tumours can lead to a radiobiological effect inconsistent with dose estimates. The aim was to assess the influence of antibody and radionuclide characteristics on the heterogeneity of dose deposition. Quantitative images of the temporal and spatial heterogeneity of a range of antibodies in tumour were acquired using radioluminography. Subsequent registration with images of tumour morphology then allowed the delineation of viable and necrotic areas of tumour and the measurement of the antibody concentration in each area. A tumour dosimetry model then estimated the absorbed dose from 131I and 90Y in each area. Tumour-specific antibodies initially localized in the viable radiosensitive areas of tumour and then penetrated further into tumour with continued tumour accretion. Multivalent antibodies were retained longer and at higher concentrations in viable areas, while monovalent antibodies had greater mobility. In contrast, non-specific antibodies penetrated into necrotic regions regardless of their size. As a result, multivalent, specific antibodies delivered a significantly larger dose to viable cells compared with monovalent antibodies, while non-specific antibodies deposited most of the dose in necrotic areas. There was a significant difference in dose estimates when assuming a uniform dose deposition and accounting for heterogeneity. The dose to the viable and necrotic areas also depended on the properties of the radionuclide where antibodies labelled with 131I generally delivered a higher dose throughout the tumour even though the instantaneous dose-rate distribution for 90Y was more uniform. The extent of heterogeneity of dose deposition in tumour is highly dependent on the antibody characteristics and radionuclide properties, and can enhance therapeutic efficacy through the selective dose delivery to the radiosensitive areas of tumour.


Alteration of the Antitumor Immune Response by Cancer-Associated Fibroblasts.
Among cells present in the tumor microenvironment, activated fibroblasts termed cancer-associated fibroblasts (CAFs), play a critical role in the complex process of tumor-stroma interaction. CAFs, one of the prominent stromal cell populations in most types of human carcinomas, have been involved in tumor growth, angiogenesis, cancer stemness, extracellular matrix remodeling, tissue invasion, metastasis, and even chemoresistance. During the past decade, these activated tumor-associated fibroblasts have also been involved in the modulation of the anti-tumor immune response on various levels. In this review, we describe our current understanding of how CAFs accomplish this task as well as their potential therapeutic implications.


Phenomenology of photoinduced processes in the ionic sol-gel-based azobenzene materials.
Very recently, supramolecular azobenzene-containing materials have been demonstrated to be effective for holographic inscription of surface relief gratings. High efficiency of grating formation in these materials is advantageously combined with easy material preparation because of the supramolecular principle of building blocs combination, availability of chemical components, and good film-forming properties. The materials show great promise for wide optical applications. Here, one type of material formulation based on ionic complexes of poly(aminosiloxane) is experimentally investigated concerning the induction of birefringence, efficiency of relief formation, and thermal stability of surface structures. Properties of the material were changed on the molecular level by varying the azobenzene content and on the macro level by varying chemical processing conditions. The results are discussed in terms of cross-linking and plasticizing effects caused by residual solvent and the low-molecular-weight azobenzene component. An improvement of both the efficiency of grating formation and their thermal stability by these means has been demonstrated. The results can be adapted to other azobenzene-containing materials. In addition, a drastic change of films solubility has been observed upon irradiation.


Total pelvic exenteration with preservation of fecal continence.
Total pelvic exenteration may be required in the management of locally advanced or recurrent pelvic malignancy. Although prolonged survival may be achieved, the morbidity of this procedure is substantial. Many of the complications associated with total pelvic exenteration are related to the perineal wound, the necessity for two cutaneous stomas, and the creation of a empty pelvis that often has been previously irradiated. In selected cases, perineal preservation with restoration of coloanal continuity may significantly reduce postoperative morbidity. We report four cases of recurrent pelvic malignancy treated by total pelvic exenteration with preservation of fecal continence.


Gynecologic Risk Mitigation Considerations for Long-Duration Spaceflight.
INTRODUCTION: As NASA and its international partners, as well as the commercial spaceflight industry, prepare for missions of increasing duration and venturing outside of low-Earth orbit, mitigation of medical risk is of high priority. Gynecologic considerations constitute one facet of medical risk for female astronauts. This manuscript will review the preflight, in-flight, and postflight clinical evaluation, management, and prevention considerations for reducing gynecologic and reproductive risks in female astronauts.METHODS: Relevant gynecological articles from databases including Ovid, Medline, Web of Science, various medical libraries, and NASA archives were evaluated for this review. In particular, articles addressing preventive measures or management of conditions in resource-limited environments were evaluated for applicability to future long-duration exploration spaceflight.RESULTS: Topics including abnormal uterine bleeding, anemia, bone mineral density, ovarian cysts, venous thromboembolism, contraception, fertility, and health maintenance were reviewed. Prevention and treatment strategies are discussed with a focus on management options that consider limitations of onboard medical capabilities.DISCUSSION: Long-duration exploration spaceflight will introduce new challenges for maintenance of gynecological and reproductive health. The impact of the space environment outside of low-Earth orbit on gynecological concerns remains unknown, with factors such as increased particle radiation exposure adding complexity and potential risk. While the most effective means of minimizing the impact of gynecologic or reproductive pathology for female astronauts is screening and prevention, gynecological concerns can arise unpredictably as they do on Earth. Careful consideration of gynecological risks and potential adverse events during spaceflight is a critical component to risk analysis and preventive medicine for future exploration missions.Steller JG, Blue RS, Burns R, Bayuse TM, Antonsen EL, Jain V, Blackwell MM, Jennings RT. Gynecologic risk mitigation considerations for long-duration spaceflight. Aerosp Med Hum Perform. 2020; 91(7):543-564.


Ionic liquids: nondestructive, nonvolatile imaging fluids for submicrometer-scale monolayer patterns.
A method for visualizing submicrometer-scale patterns of approximately 1.0-nm-thick monolayers terminated with CF(3) and CH(3) groups using an ionic liquid (IL) is described. Bis(hydroxyethyl)dimethylammonium methanesulfonate (BHDAMS) was spin-cast onto the photolithographically patterned samples. The BHDAMS wetted the photodecomposed regions selectively. Pattern widths of the mask ranged from 500 nm to 10 microm, and the IL-replicated patterns were observed using optical and laser microscopy. The nonvolatile BHDAMS had sufficient contrast to image submicrometer-scale patterns of monolayers over large areas. We note that this imaging technique involves no damage and is compatible with readily available laboratory equipment.


Blunt trauma and operative care in microgravity: a review of microgravity physiology and surgical investigations with implications for critical care and operative treatment in space.
The assembly of the International Space Station in a low earth orbit will soon become a reality. The National Aeronautics and Space Administration envisions inhabited lunar bases and staffed missions to Mars in the future. Increasing numbers of astronauts, construction of high-mass structures, increased extra-vehicular activity, and prolonged if not prohibitive medical evacuation times to earth underscore the need to address requirements for trauma care in nonterrestrial environments. A search was carried out to review the relevant literature in the MEDLINE and SPACELINE databases. All related Technical, Corporate, and Flight Test Reports in the KRUG Life Sciences corporate library were also reviewed. Bibliographies of all articles were then reviewed from these papers to identify additional pertinent literature. Senior Russian investigators reviewed the Russian literature and translated Russian publications when appropriate. Personal communication and discussion with active microgravity investigators and ongoing microgravity research supplemented published reports. A large volume of data exist to document the multiple detrimental physiologic effects of microgravity exposure on human physiology. Organs systems such as cardiovascular, neurohumoral, immune, hematopoetic, and musculoskeletal systems may be particularly affected. These physiologic changes suggest an impaired ability to withstand major systemic trauma. Observational data also suggest adverse changes in numerous aspects of response to wounding and injury, and in areas such as the behavior of hemorrhage, microbiologic flora, and wound healing. In addition to an increased volume of ongoing and anticipated basic science research in microgravity physiology, preliminary studies of clinical diagnosis and therapy have been carried out in microgravity and microgravity laboratories. The feasibility of a wide range of ancillary critical care techniques has been verified in the parabolic flight model of microgravity. Although Russian investigators first performed laparotomies on rabbits in parabolic flight in 1967, only recently have American investigators demonstrated the reproducible feasibility of open and endoscopic surgical procedures under general anesthetic in animal models in a microgravity environment. With appropriate instrumentation and personnel, the majority of resuscitative and surgical interventions required to stabilize a severely injured astronaut are feasible in a microgravity environment. Onboard limitations in mass, volume, and power that are ever present in any spacecraft design will limit the realistic capabilities of the medical system. Standard proved and tested trauma and operative management protocols will constitute the basis for extra-terrestrial care. Surgeons should familiarize themselves with the microgravity environment and remain active in planning trauma care for the continued exploration of space.


General practitioners' reported application of DSM major depressive disorder criteria after removal of the bereavement exclusion criterion.
The removal of the bereavement exclusion criterion from major depressive disorder (MDD) in the 5th edition of Diagnostic and Statistical Manual of Mental Disorders generated concerns of over-diagnosing grief. Eight Australian General Practitioners (GPs) were interviewed to explore their application of MDD criteria to recently-bereaved individuals. Thematic analysis found GPs were unaware of the change and reluctant to apply MDD criteria two weeks post-bereavement. Depressive symptoms were viewed as natural grief, with diagnostic labels seen as unnecessary for patient-centered care. Our findings suggest new MDD criteria not being strictly applied by GPs, or no anticipated over-inflation of MDD diagnoses post-bereavement.


[Assessment of the economic savings and advantages of Productive Development Partnerships].
The policy for Productive Development Partnerships emerged in Brazil as a Federal Government strategy to strengthen the Health Economic-Industrial Complex. Although the first partnership dates back to 2009, the regulatory framework was only consolidated in 2014, when eight policy objectives were described. Of these, this article is intended to specifically evaluate the fourth objective: "to protect the interests of the Public Administration and society by seeking economic savings and advantage, considering prices, quality, technology, and social benefits". An assessment of the policy results was performed through a mixed methodological approach, by proposing four assessment indicators. The quantative analysis results confirmed a reduction in the purchase price for 37 of the 39 drugs assessed after the policy implementation, while there was an increase in the amounts purchased in 38 of the 39 drugs. On the other hand, the qualitative analysis revealed a lack of planning by public administrators and lack of compliance with the policy guidelines related to the principle of advantageousness. Approximately 40% of the drugs studied did not undergo a health technology assessment by the Brazilian National Commission for the Incorporation of Technologies in the Unified Health System, raising doubts with regards to the advantage for the Public Administration, which is measured by the cost-effectiveness of the drugs incorporated by the policy.


[Sickle cell disease: exotic disease or a Belgian public health problem?].
Sickle cell disease is a genetic disorder involving the haemoglobin designated as haemoglobin S, an autosomic recessive hereditary disease. It is the most frequent hereditary disease in sub-Saharan Africa, however epidemiological studies performed with a systematic neonatal screening in Brussels and Liège have proven that more than one neonate over 2.000 has a sickle cell disease. If this amount is significant, at the level of each physician the number of patient-contacts will be weak. Another aspect of the disease is the variability in its expression: some patients suffer from multiple and chronic organ alterations while other suffer also from acute events which might lead to death if not treated appropriately. The poor experience of each physician, the lack of the disease knowledge by the population, the symptoms complexity, and the socio-economical aspects of sickle cell disease explain that it can be considered as an "exotic" disease but also as a public health problem. A global and dedicated approach of the patient as a whole must be implemented. This is the reason for the existence of the "Réseau des Hémoglobinopathies": http://www.redcellnet.be/.


The potential of SiK® fertilization in the resilience of chestnut plants to drought - a biochemical study.
Silicon is an essential mineral nutrient, that plays a crucial role in the metabolic, biochemical, and functional mechanisms of many crops under environmental stress. In the current study, we evaluated the effect of SiK® fertilization on the biochemical defense response in plants exposed to water stress. Castanea sativa plants were fertilized with different concentrations of potassium silicate (0, 5, 7.5, and 10 mM of SiK®) and exposed to a non-irrigation phase and an irrigation phase. The results indicate that silicon promoted the synthesis of soluble proteins and decreased the proline content and the oxidative stress (reduced electrolyte leakage, lipid peroxidation, and hydrogen peroxide accumulation) in tissues, due to an increase in ascorbate peroxidase, catalase, and peroxidase activity, which was accompanied by the rise in total phenol compounds and the number of thiols under drought conditions. This study suggests that exogenous Si applications have a protective role in chestnut plants under water deficit by increasing their resilience to this abiotic stress.


[A bronchial mucous gland adenoma resected by endoscopic procedure].
Surgical resection is usually performed for the treatment of endobronchial tumors. This case describes the use of endoscopic resection as an initial treatment, allowing to spare lung parenchyma. A patient was admitted to the emergency unit with right lower lobe pneumonia. A thoracic CT-scan and subsequent bronchoscopy revealed an intrabronchial tumor between the right main and intermediate bronchus. Biopsies were non-diagnostic and a PET-scanner did not find any abnormalities. Surgical resection was initially proposed but would have required a right upper lobectomy. The patient had stage 2 (moderate) chronic obstructive pulmonary disease (GOLD classification). Because of this, we decided to perform an endoscopic resection to obtain further histology and hopefully achieve total removal. Under conscious sedation, the resection by argon plasma coagulation with a flexible bronchoscope was realized without any complication. The histological diagnosis was a bronchial mucous gland adenoma. This case emphasizes the role of multidisciplinary discussion when considering suitability of local resection of tumors by an endobronchial procedure rather than a surgical resection.


Source profiles of particulate organic matters emitted from cereal straw burnings.
Cereal straw is one of the most abundant biomass burned in China but its contribution to fine particulates is not adequately understood. In this study, three main kinds of cereal straws were collected from five grain producing areas in China. Fine particulate matters (PM2.5) from the cereal straws subjected to control burnings, both under smoldering and flaming status, were sampled by using a custom made dilution chamber and sampling system in the laboratory. Element carbon (EC) and organic carbon (OC) was analyzed. 141 compounds of organic matters were measured by gas chromatography-mass spectrum (GC-MS). Source profiles of particulate organic matters emitted from cereal straw burnings were obtained. The results indicated that organic matters contribute a large fraction in fine particulate matters. Levoglucosan had the highest contributions with averagely 4.5% in mass of fine particulates and can be considered as the tracer of biomass burnings. Methyloxylated phenols from lignin degradation also had high concentrations in PM2.5, and contained approximately equal amounts of guaiacyl and syringyl compounds. beta-Sitostrol also made up relatively a large fraction of PM2.5 compared with the other sterols (0.18%-0.63% of the total fine particle mass). Normal alkanes, PAHs, fatty acids, as well as normal alkanols had relatively lower concentrations compared with the compounds mentioned above. Carbon preference index (CPI) of normal alkanes and alkanoic acids showed characteristics of biogenic fuel burnings. Burning status significantly influenced the formations of EC and PAHs. The differences between the emission profiles of straw and wood combustions were displayed by the fingerprint compounds, which may be used to identify the contributions between wood and straw burnings in source apportionment researches.


Water and electrolyte replacement during repeated days of work in the heat.
In an attempt to determine the value of replacing sweat losses with and electrolyte solution, 12 subjects (2 women and 10 men) were dehydrated (minus 3% body weight) on 5 successive days. During one 5-d sequence, the subjects replaced fluid losses with a glucose-electrolyte solution, while water was the only fluid ingested during a second 5-d series. With the exception of the drink, daily ionic and caloric intakes were identical for the two 5-d conditions. Measurements of water and electrolyte losses in sweat and urine showed a positive balance in body Na+, K+, and Cl- during both the water (W) and electrolyte solution (ES) treatments. Subjects accumulated significantly more Na+ during the W experiments (392 mEq/5 d) than when the electrolyte solution was ingested (334 mEq/5 d). As a result, the extracellular fluid compartment, represented by plasma volume, increased 12.2 and 9.0% during the 5-d sequence of the W and ES trials, respectively. It was concluded that the addition of electrolytes to drinking water is of minimal value for subjects who dehydrated (-3%) on repeated days and are permitted to ingest food and drink libitum


Comparison of supine and prone craniospinal irradiation in children with medulloblastoma.
To compare port film rejection and treatment outcome according to craniospinal irradiation (CSI) position for medulloblastoma. We retrospectively searched for patients ≤19 years treated with CSI for medulloblastoma at 1 department. We collected the following data: age; sex; risk group; need for general anesthesia; radiation therapy (RT) dose and fractionation; and the acceptance or rejection of weekly port films during treatment. We also collected data on outcomes, including neuraxis recurrence and possible complications such as myelitis. Of 46 children identified, 23 were treated prone (median age, 8.1 years) and 23 supine (median age, 7.2 years). High-risk disease was seen in 26% of prone and 35% of supine patients (P = .25). There was no difference in use of general anesthesia between those treated prone versus supine (57% vs 61%). The rejection rate of cranial port films in the prone position was 35%, which was significantly higher than the rate of 8% in patients treated supine (P < .0001). The 5-year progression-free (P = .37) and overall survival (P = .18) rates were 62% and 67% for prone and 76% and 84% for supine patients. There were no isolated junctional failures or radiation myelitis in either CSI position. The supine position for CSI was found to have similar survival outcomes compared with the prone position. A higher proportion of rejected cranial port films was seen in children treated in the prone position.


Babesia vogeli in dogs in Chile.
We report the presence of Babesia vogeli in dogs in Chile. During two surveillance campaigns separated by a year, sixty-three blood samples from free-ranging rural dogs in Coquimbo, Chile, were analysed through conventional PCR screening of the 18S rRNA for Babesia species. Sequencing confirmed the presence of Babesia vogeli in 6.3% of the tested animals, with positive cases in both years. All the sequences showed 100% nucleotide sequence identity among them and 99.8% with other previously published sequences from dogs. No clinical signs or haematological abnormalities other than thrombocytopenia were found in the parasitized individuals. This is the first report of a canine piroplasmid in Chile.


The Nuclear Lamina.
Lamins interact with a host of nuclear membrane proteins, transcription factors, chromatin regulators, signaling molecules, splicing factors, and even chromatin itself to form a nuclear subcompartment, the nuclear lamina, that is involved in a variety of cellular processes such as the governance of nuclear integrity, nuclear positioning, mitosis, DNA repair, DNA replication, splicing, signaling, mechanotransduction and -sensation, transcriptional regulation, and genome organization. Lamins are the primary scaffold for this nuclear subcompartment, but interactions with lamin-associated peptides in the inner nuclear membrane are self-reinforcing and mutually required. Lamins also interact, directly and indirectly, with peripheral heterochromatin domains called lamina-associated domains (LADs) and help to regulate dynamic 3D genome organization and expression of developmentally regulated genes.


Evaluation of the effect of salts on chemical, structural, textural, sensory and heating properties of cheese: Contribution of conventional methods and spectral ones.
Chemical composition, sensory characteristics, textural and functional properties are among the most important characteristics, which directly relates to the global quality of cheese and to consumer acceptability. A number of factors including milk composition, processing conditions and salt content, influences these properties. The past decades many investigations were performed on the possibilities to reduce salt content of cheese due to its adverse health effects, the current lifestyle and the awareness of the consumers for nutrition quality products. Due to the multiple potential effects of reducing NaCl (simple reduction or substitution) on cheese attributes, it is of utmost importance to identify and understand those effects in order to control the global quality and safety of the final product. In the present review a collection of the different results and conclusions drawn after studying the effect of salts by conventional (e.g. wet chemistry) and instrumental (e.g. spectral) methods on chemical, structural, textural, sensory and heating properties of cheese are presented.


Continuous Indirect Calorimetry in Critically Injured Patients Reveals Significant Daily Variability and Delayed, Sustained Hypermetabolism.
Previous studies have used using Indirect Calorimetry (IC) with solitary or sparse measurements of resting energy expenditure (REE). This "snapshot" may not capture the dynamic nature of metabolic requirements. Using continuous IC, we describe the variation of REE during the first days in the intensive care unit. Injured adults (≥18 years) requiring mechanical ventilation from March 2018 to September 2018 were enrolled. IC was initiated within 4 days of admission and continuous REE recorded until 14 days, extubation, or death. Multiple 10-minute periods collected during steady state were used to calculate daily REE maximum, minimum, average, and variability [(REEmax - REEmin/2)/average REE]. We included 55 patients. Median age was 38 [27-58] years, 38 (69%) were male, body mass index was 28 [25-33] kg/m2 , and Acute Physiology and Chronic Health Evaluation II was 17 [14-24]. Mechanism of injury was: blunt (n = 38, 69%), penetrating (n = 9, 16%), and burn (n = 8, 15%). Average REE increased gradually from 1,663 kcal [1,435-2,143] to a maximum of 2,080 [1,701-2,336] on day 7, a relative 25% increase, which was sustained through day 14. REE variability ranged 8%-13% and was not reliably predicted by fever, tachycardia, elevated intracranial pressures, hypertension, or hypotension. In critically injured patients, steady-state REE measurements display fluctuations over a 24-hour period and demonstrate a gradual rise over the first few days after injury. Continuous REE, if available, is recommended for more precise matching of energy delivery to metabolic requirements.


Investigation of the Spatial Generation of Stimulated Raman Scattering Using Computer Simulation and Experimentation.
Stimulated Raman scattering is a phenomenon with potential use in providing real-time molecular information in three-dimensions (3D) of a sample using imaging. For precise imaging, the knowledge about the spatial generation of stimulated Raman scattering is essential. To investigate the spatial behavior in an idealized case, computer simulations and experiments were performed. For the computer simulations, diffraction theory was used for the beam propagation complemented with nonlinear phase modulation describing the interaction between the light and matter. For the experiments, a volume of ethanol was illuminated by an expanded light beam and a plane inside the volume was imaged in transmission. For generating stimulated Raman scattering, a pump beam was focused into this volume and led to a beam dump after passing the volume. The pulse duration of the two beams were 6 ns and the pump beam energy ranged from 1 to 27 mJ. The effect of increasing pump power on the spatial distribution of the Raman gain and the spatial growth of the signal at different interaction lengths between the beam and the sample was investigated. The spatial width of the region where the stimulated Raman scattering signal was generated for experiments and simulation was 0.21 and 0.09 mm, respectively. The experimental and simulation results showed that most of the stimulated Raman scattering is generated close to the pump beam focus and the maximum peak of the Stokes intensity spatially comes shortly after the peak of the pump intensity.


Trust and subjective knowledge influence perceived risk of lead exposure.
Lead exposure is a persistent environmental hazard that poses risks to human health. But motivating protective action is challenging with this low visibility hazard whose health effects are often subtle and chronic. Higher risk perception is generally associated with taking protective measures, so public health efforts prioritize risk messaging. Yet, little is known about perceptions of lead exposure risk among the U.S. public. Using cross-sectional data from a national survey of 1035 U.S. residents, we measured the role of trust in government management of lead and subjective knowledge about lead as predictors of perceived risk of lead exposure, controlling for demographic and environmental factors. We also assessed if subjective knowledge moderated the relationship between trust and perceived risk. Our results reveal positive relationships between trust in government management of lead, subjective knowledge about lead, and risk perception, which we attribute in part to the important role government agencies play in secondary prevention, or communicating the risks of environmental lead exposure. We also found that younger people and people living in a house built before lead paint regulations passed in 1978 perceived higher lead risks. Our findings suggest that general communication about lead risks should aim to increase people's subjective knowledge in a consistent and balanced way that improves trust in government messengers.


The erythrocyte sedimentation rate in general practice: clinical assessment based on case histories.
Thirteen case histories were mailed to 273 general practitioners to study the clinical assessment of the ESR. Participants were asked to state their reference limits for the ESR, as well as action values for the ESR in several clinical situations typical of primary care. The action value should represent the minimal ESR change from a given value necessary to initiate some kind of action towards the patient. The response rate was 76%. In most case histories, half the general practitioners reacted on an ESR change of 10 mm h-1 or less, which is usually due to analytical and biological variation, thus underlining the need for good analytical quality. In general the response was of the same magnitude irrespective of type of case history, i.e. whether the ESR was used in case finding, in diagnosis, or in follow-up. Estimation of the reference limit displayed considerable variation, and knowledge of a previous 'normal' ESR was of minor clinical importance. Furthermore, we found substantial variation regarding the change in ESR necessary to take action in different clinical situations. In principle, for many general practitioners the action value increased as the given ESR increased whereas others reacted on a constant change in ESR, or the change necessary to take action depended on the clinical situation. We conclude that both the different assessments as to the clinical significance of the ESR, and the unawareness of the significance of analytical and biological variation indicate that guidelines for rational use are needed.


Enteroinsular axis.
A physiological role for GIP as an insulinotropic hormone involved in the enteroinsular axis has been established and ingestion of glucose, fatty acids and certain amino acids will produce an increase in circulating IR-GIP levels. The insulinotropic action of GIP is glucose concentration dependent in normal animals. A role for GIP in NIDDM is equivocal although several studies have demonstrated elevated serum levels. Animal models have indicated a disturbance of GIP receptor function associated with hyperinsulinaemia, i.e. lowering of the minimum glucose concentration at which GIP is insulinotropic.


Contrast-induced acute kidney injury: A review of practical points.
Contrast-induced acute kidney injury (CI-AKI) is one of the most common causes of AKI in clinical practice. CI-AKI has been found to be strongly associated with morbidity and mortality of the patients. Furthermore, CI-AKI may not be always reversible and it may be associated with the development of chronic kidney disease. Pathophysiology of CI-AKI is not exactly understood and there is no consensus on the preventive strategies. CI-AKI is an active research area thus clinicians should be updated periodically about this topic. In this review, we aimed to discuss the indications of contrast-enhanced imaging, types of contrast media and their impact on nephrotoxicity, major pathophysiological mechanisms, risk factors and preventive strategies of CI-AKI and alternative non-contrast-enhanced imaging methods.


Structural and functional brain changes after glucocorticoid therapy in thyroid-associated ophthalmopathy.
To investigate the brain structural and functional alterations in patients with thyroid-associated ophthalmopathy (TAO) before and after glucocorticoid therapy, using voxel-based morphometry (VBM) as well as resting-state functional magnetic resonance imaging (MRI) with amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo). Between 2019 and 2022, 32 patients with TAO and 23 healthy controls were recruited to undergo pre-therapy MRI scans in Nanjing, China. Intravenous glucocorticoid therapy was administered to all patients. Twenty-six of the patients were available for rescanned MRI three months after the end of therapy. The VBM, ALFF and ReHo methods were used to evaluate the brain structural and functional differences. Before therapy, TAO patients showed significantly decreased gray matter volume in left orbital part of superior frontal gyrus (ORBsup) and medial superior frontal gyrus (SFGmed) than healthy controls. Patients had higher ALFF values in bilateral gyrus rectus and olfactory cortex as well as lower values in bilateral cuneus. Besides, the patients showed decreased ReHo values in bilateral lingual gyrus. After therapy, increased gray matter volume in left anterior cingulate gyrus and SFGmed, increased ALFF values in bilateral cuneus and superior occipital gyrus, as well as increased ReHo values in bilateral SFGmed were found in TAO patients compared to the pre-therapy cohort. Compared to controls, decreased gray matter volume in left ORBsup was observed in post-therapy TAO patients. Our results indicated that TAO might cause functional and structural deficits in the visual and emotional regions of the brain, with recovery in the former and partial restoration in the latter after effective glucocorticoid therapy. These findings may lead to a deeper understanding of the pathophysiological mechanism behind TAO.


Incomplete epithelial-mesenchymal transition in p16-positive squamous cell carcinoma cells correlates with β-catenin expression.
The epithelial-mesenchymal transition (EMT) is suggested to be a crucial factor for the development of an invasive and metastatic cell phenotype, which is characterized by down-regulation of epithelial adhesive proteins (e.g. E-cadherin) and induction of mesenchymal proteins (e.g. vimentin). Therefore, there is a great clinical interest to specify this phenotype. Different growth factors induce EMT, such as epithelial growth factor (EGF) and transforming growth factor beta 1 (TGFβ1). The role of EMT in human papilloma virus (HPV)-positive squamous cell carcinoma (SCC) is still not understood. The aim of this study was to investigate the expression pattern in p16-positive and -negative SCC cells of vimentin, β-catenin and E-cadherin after stimulation with growth factors. We incubated the p16-positive CERV196 and p16-negative HNSCC22B SCC cell lines with EGF and EGF/TGFβ1 (10 ng/ml) and detected E-cadherin, vimentin and β-catenin by immunocytochemistry and enzyme-linked immunosorbent assay after 5, 24 and 96 h. We found a low expression of vimentin in all studied tumor cell lines. The negative control of HNSCC22B cells showed a higher intrinsic level of membranous E-cadherin and β-catenin. We found statistically significant EGF/TGFβ1-induced expression of vimentin dependent on incubation time in p16-negative HNSCC22B cells. Particularly in the presence of EGF, we detected an increase of β-catenin and vimentin expression in p16-positive SCC tumor cell lines in addition to induced cell scattering and unexpected expression of E-cadherin. In conclusion, E-cadherin, β-catenin and vimentin expression are important features to characterize EMT-like events. We were able to show incomplete EGF-induced EMT with β-catenin expression in p16-positive SCC. Extended studies are required to investigate the mechanistic role of EMT markers, especially in p16-positive SCC, in order to develop new anti-SCC therapies to block EMT progression.


[Enzymetic synthesis and characterization of a carnosine analogue in non-aqueous solvent].
Carnosine (beta-Ala-L-His) has high antioxidant activity, and it is widely used in biology, chemical engineering, medicine and other fields. Its analogue syntheised in non-aqueous solvent and catalyzed by enzymes is high-effective but low-price, so it has great prospect. Here, we synthesized a carnosine analogue imidazole 4(5)-alanylamide-5(4)-carboxylic acid with imidazole-4,5-dicarboxylic acid and L-Alanine as substrates, alpha-chymotrypsin as catalyst in tetrahydrofuran (THF) solvent. Based on the orthogonal experiments, the optimized synthetic conditions are 4,5-dicarboxylic acid: L-alanine = 1:3 (m/m), alpha-chymotrypsin: substrates (4,5-dicarboxyl acid and L-alanine) = 1:200 (m/m), pH 8 phosphate buffer:THF = 1.6:10 (V/V), reaction temperature 35 degrees C, time 1.5 h. We separated the product with silica gel G60 thin-layer chromatography (TLC), and a new spot appeared at Rf (ratio to front) = 0.81; then the new spot was purified and characterized with UV spectra, high performance liquid chromatogram (HPLC) and 13C NMR (13C nuclear magnetic resonance). The UV spectra shows a new absorption peak at 310 nm, and the peak in 253 nm is largely strengthened; HPLC reserve times are all 4.5 min at 253 nm, 310 nm, 330 nm; 13C NMR shows 8 carbons. Combing with the catalytic mechanism of alpha-chymotrypsin, structure of the analogue is confirmed, i.e., imidazole 4(5)-alanylamide-5(4)-carboxylic acid.


Axitinib in metastatic renal cell carcinoma: beyond the second-line setting.
Treatment options for advanced and metastatic renal cell carcinoma have advanced considerably in the past decade with the approval of several targeted agents, including axitinib. Axitinib is a potent and selective inhibitor of VEGFRs 1-3, and is well established as second-line treatment. This article summarizes factors to be considered when administering axitinib, such as individualized dose titration and axitinib-associated adverse events, in order to retain patients longer on treatment, which would likely lead to improved efficacy outcomes. In addition, potential clinical perspectives for axitinib beyond the second-line setting, including its role in the first-line setting, sequential therapy, neoadjuvant and adjuvant therapies, and combination therapy with immunotherapy, in particular, immune checkpoint inhibitors, are discussed.


Biological embedding of childhood adversity: from physiological mechanisms to clinical implications.
Adverse psychosocial exposures in early life, namely experiences such as child maltreatment, caregiver stress or depression, and domestic or community violence, have been associated in epidemiological studies with increased lifetime risk of adverse outcomes, including diabetes, heart disease, cancers, and psychiatric illnesses. Additional work has shed light on the potential molecular mechanisms by which early adversity becomes "biologically embedded" in altered physiology across body systems. This review surveys evidence on such mechanisms and calls on researchers, clinicians, policymakers, and other practitioners to act upon evidence. Childhood psychosocial adversity has wide-ranging effects on neural, endocrine, immune, and metabolic physiology. Molecular mechanisms broadly implicate disruption of central neural networks, neuroendocrine stress dysregulation, and chronic inflammation, among other changes. Physiological disruption predisposes individuals to common diseases across the life course. Reviewed evidence has important implications for clinical practice, biomedical research, and work across other sectors relevant to public health and child wellbeing. Warranted changes include increased clinical screening for exposures among children and adults, scale-up of effective interventions, policy advocacy, and ongoing research to develop new evidence-based response strategies.


Purification and properties of cinnamoyl-CoA reductase and cinnamyl alcohol dehydrogenase from poplar stems (Populus X euramericana).
Cinnamoyl-CoA reductase and cinnamyl alcohol dehydrogenase were purified to apparent homogeneity from poplar stems (Populus euramericana) and their main properties were studied. Only one form was identified for each enzyme. The reductase corresponded to one polypeptide of molecular weight 36 000 and the cinnamyl alcohol dehydrogenase was constituted of two identical subunits of molecular weight 40 000. These characteristics are in agreement with most of the data obtained for the same enzymes isolated from other plants. The two reductive enzymes are inhibited by thiol reagents and a metal chelator 1,10-phenanthroline. The isoelectric point of the reductase (pH 7.5) and of the dehydrogenase (pH 5.6) were determined by chromatofocusing. The cinnamoyl-CoA reductase exhibit a decreasing affinity towards feruloyl-CoA, sinapoyl-CoA and p-coumaroyl-CoA. The cinnamyl alcohol dehydrogenase, which catalyses the reduction of the three cinnamaldehydes, exhibits its highest efficiency towards coniferaldehyde. In spite of differences in the monomeric composition of lignins from xylem and sclerenchyma the reductive enzymes isolated from these two lignified tissues exhibit the same substrate specificity. Consequently, they do not play an important role in the qualitative control of lignins in poplar tissues.


Lymphoedema 3: the available treatments for lymphoedema.
The third article in this series describes the treatment available to sufferers of lymphoedema in the UK. Lymphoedema is a condition that cannot be cured and requires lifelong treatment to control symptoms that, if left untreated, would progressively worsen. The aim of treatment is to stabilize the oedema and empower the patient with the necessary skills to undertake self-care. Four components of treatment are used to achieve this goal: care of the skin, compression and support, lymphatic massage and exercise. The purpose of each treatment will be explained and supported with research findings. Examination of the literature reveals a weak evidence base supporting treatment practice in this country. The majority of evidence relates to vascular insufficiency and findings from abroad. A brief account will be made of the reasons for this and how the trend is changing.


Mass analyzed threshold ionization spectroscopy of p-fluorostyrene.
Adiabatic ionization energy (AIE) and two-color threshold ion vibrational spectra of p-fluorostyrene have been measured by mass analyzed threshold ionization (MATI) method via three different intermediate levels in the first excited state, vibrationless S1 origin, 42(1)41(1), and 23(1) vibronic levels. Features of the ion vibrational spectra indicates that the geometry of the molecular ion including the conformation of the vinyl chain in the ionic ground state (D0) is almost identical to that of its neutral ground state (S0), and ionization has very little effect on the vibrational potentials of the aromatic ring modes. Comparison of the AIE with the reported value of styrene shows that fluorination at the para position of the aromatic ring has little effect on energy of the electron ejected in ionization process from the styrene chromophore.


Effect of exogenous nitric oxide during cardiopulmonary bypass on lung postperfusion histology.
We tested the hypothesis that nitric oxide (NO) administered during cardiopulmonary bypass (CPB) would preserve platelets and prevent postperfusion lung changes. Ten anesthetized Yorkshire pigs were put on normothermic CPB (right atrium to aorta) with a roller pump and membrane oxygenator for 1 hour. In the study group (n = 5), NO was delivered in the oxygenator's gas inflow line with a MiniNO system at 5-10 ppm throughout CPB. In controls (n = 5), NO was not used. Crystalloid solution and norepinephrine were used to maintain blood pressure > or = 60 mm Hg. Fifteen minutes after CPB termination, all pigs were killed with intravenous potassium chloride and exsanguinated via the right atrium. Organ samples were put in formalin solution, processed in paraffin blocks, and stained with hematoxylin and eosin. We did not observe any thrombi in any perfusion system. There were no differences observed in platelet counts and aggregation ability to ADP and collagen, or in neutrophil counts between groups. Bleeding times were similar between groups before and after CPB. Also, there was no significant difference in factor XIIa and fibrinopeptide A levels between groups. Methemoglobin did not exceed normal levels. Lungs were devoid of neutrophils after perfusion in NO-treated pigs, whereas many neutrophils were present in the respiratory membrane of controls. Low-dose exogenous NO in the oxygenator's gas intake has no demonstrable effect on platelet number or function, but prevents neutrophil adhesion to lungs with a possible beneficial effect on postperfusion pulmonary morbidity.


Adults scan own- and other-race faces differently.
It is well established that individuals show an other-race effect (ORE) in face recognition: they recognize own-race faces better than other-race faces. The present study tested the hypothesis that individuals would also scan own- and other-race faces differently. We asked Chinese participants to remember Chinese and Caucasian faces and we tested their memory of the faces over five testing blocks. The participants' eye movements were recorded with the use of an eye tracker. The data were analyzed with an Area of Interest approach using the key AOIs of a face (eyes, nose, and mouth). Also, we used the iMap toolbox to analyze the raw data of participants' fixation on each pixel of the entire face. Results from both types of analyses strongly supported the hypothesis. When viewing target Chinese or Caucasian faces, Chinese participants spent a significantly greater proportion of fixation time on the eyes of other-race Caucasian faces than the eyes of own-race Chinese faces. In contrast, they spent a significantly greater proportion of fixation time on the nose and mouth of Chinese faces than the nose and mouth of Caucasian faces. This pattern of differential fixation, for own- and other-race eyes and nose in particular, was consistent even as participants became increasingly familiar with the target faces of both races. The results could not be explained by the perceptual salience of the Chinese nose or Caucasian eyes because these features were not differentially salient across the races. Our results are discussed in terms of the facial morphological differences between Chinese and Caucasian faces and the enculturation of mutual gaze norms in East Asian cultures.


Personalized Nutrition Advice: Preferred Ways of Receiving Information Related to Psychological Characteristics.
The primary goal of this study is to be able to discern specific types of consumers in terms of their psychosocial characteristics who may need different ways of receiving dietary advice. Knowing these types will enable a better fit of advice to consumers' psychosocial characteristics, hereby stimulating healthy eating as the probability of compliance to the advice can potentially increase. The study draws upon several psychological theories to distinguish unique underlying factors that can subsequently be used to personalize nutrition information for consumers. A number of general psychological scales (self-regulation, action and coping self-efficacy, social comparison, intrinsic motivation, health info processing, need for cognition and for affect, and regulatory focus) are filled out by 988 respondents, including their preferences for receiving personalized forms of nutrition advice. The set of joint items from various psychological constructs is analyzed using a Principal Component Analysis to find underlying psychological characteristics. The PCA produces four components (explaining 51% of variation), that could be interpreted as 'intrinsic interest and capabilities for healthy eating,' 'perceived difficulty to eat healthily,' 'self-worth insecurity,' and 'seeking positive challenges,' respectively. By means of a Logistic Regression these components are able to predict preferences for different forms of receiving nutrition advice. This first component shows that a mind set for maintaining a healthy diet goes together with an interest in receiving an advice on what do to and on how that will affect one's health. The second component predicts a preference for a fixed moment to receive information/advice. This may be a strategy of those that perceive difficulties to eat healthily, to help them control their healthy food intake. The insecurity that the third component models seems to lead to a wish for receiving specific advice about their health situation at fixed moments in time. The fourth component is a small component, therefore its prediction of a wish for an advice focussing on prevention of negative consequences is probably not a strong result. The study does point out that there appear different psychosocial types of consumers, that may benefit by being addressed according to their preference for receiving nutrition advice on specific moments, of a specific level of detail or pointing at the type of consequences the advice has. A better fit of the advice to the psychosocial characteristics of the recipient, captured in the identified components in the current study, may lead to an increase in compliance, although that will have to be further investigated in subsequent work.


[Influence of lesion of motor cortex on second somatosensory area emanating descending modulation on thalamic intralaminar nuclei].
The present study was undertaken to verify further the participation of motor cortex (MCtx) in the somatosensory area II(SII) emanating descending modulation of thalamic intralaminar nuclei (ILN). Neuronal responses in ILN to noxious stimulation of the superficial peroneal nerve were extracellularly recorded in 34 cats. The effects of electrical stimulating SII on nociceptive responses of neurons in ILN before and after lesion of MCtx were observed and compared. It was shown that electrical stimulation of SII obviously inhibited the nociceptive responses in the majority of neurons recorded (11/13) in ILN in the cats with MCtx intact (P < 0.05). After lesion of MCtx the inhibitory effect still remained (n = 10, P < 0.05), but weakened to a certain extent compared with that before lesion. In the animals with the lesion involving MCtx and the underlying subcortical structures electrical stimulating SII facilitated the nociceptive responses of ILN neurons (n = 7, P < 0.05). The results further support the idea that SII emanating descending modulation on ILN is in part fulfilled via MCtx.


Improving effect of Ginkgolide B on mitochondrial respiration of ischemic neuron after cerebral thrombosis in tree shrewa.
It has been known that platelet activating factor receptors (PAFR) may mediate many acute pathological responses and that PAFR antagonist Ginkgolide B (GB) possesses multiple effects, but the actions of GB on PAFR affinity and mitochondrial respiration in the ischemic neuron were unclear until now. This study explored the possible effects of GB on PAFR and the mitochondrial respiration of the neuron in the ischemic microenvironment. Thrombotic cerebral ischemia in tree shrews was induced by a photochemical reaction; changes in the regional cerebral blood flow (rCBF, using (99m)Tc tracer technique), the brain water content (specific gravimetric method), PAFR (3H-labelled PAF assay), the respiratory control rate (RCR), the phosphorus-oxygen (P/O) ratio of mitochondrial respiration (Clark oxygen electrode), mitochondrial permeability transition (MPT) pore, and the mitochondrial ultrastructure in the ischemic neurons were also observed. Data were compared between the two groups (the ischemia group vs the sham group, and the ischemia group vs the GB group). There were high affinity and low affinity sites for PAFR on the tree threws' brain cell membranes. The varying-affinity PAFR binding sites, the respiration state III, the state IV, RCR, the P/O ratio of the mitochondria, and the rCBF all decreased markedly (respectively, P < 0.01 and P < 0.05), but the water content increased (P < 0.01) in the ischemia group after the application of cerebral thrombosis. In tree shrews treated with GB (5 mg/kg i.v.) 6 hours after photochemical reaction, their PAFR binding sites and respiratory state increased markedly. The rCBF gradually increased and the brain edema ameliorated (P < 0.01) at 24h after cerebral ischemia. There were significant differences between the ischemia group and sham group (P < 0.01). In GB treated isolated neurons' mitochondria, with or without cerebral ischemia, the energy metabolism of the mitochondria had not been changed. The activation of the PAFR may play an important role in the inhibition of the mitochondrial respiration and the induction of neuronal damage after cerebral thrombosis; however, GB possesses neuroprotective effects by improving mitochondrial metabolism.


The regenerative therapies of the ankle degeneration: a focus on multipotential mesenchymal stromal cells.
The ankle degeneration ranging from focal osteochondral lesions to osteoarthritis can cause a total joint function loss. With rising life expectancy and activity of the patients, various regenerative therapies were introduced aiming to preserve the joint function via the induction of cartilage and bone repair. Here, biological events and mechanical changes of the ankle degeneration were discussed. The regenerative therapies were reviewed versus the standard surgical treatment. We especially focused on the use of mesenchymal (multipotential) stromal cells (MSCs) highlighting their dual functions of regeneration and cell modulation with an emphasis on the emerging MSC-based clinical studies. Being at an early step, more basic and clinical research is needed to optimize the applications of all ankle regenerative therapies including MSC-based methods.


Significant tracheal obstruction causing failure to wean in patients requiring prolonged mechanical ventilation: a forgotten complication of long-term mechanical ventilation.
Modern low-pressure, high-volume cuffed tracheotomy tubes have been shown to decrease tracheal injury. However, injury still occurs in patients requiring prolonged mechanical ventilation and prevents weaning, delays decannulation, prolongs hospitalization, and may totally obstruct the airway. We describe 37 patients, including the first reported case of failure to wean due to tracheal obstruction. Over a 3-year period, from September 1994 to August 1997, the hospital records of 37 patients requiring prolonged mechanical ventilation (> 4 weeks) and found to have tracheal obstruction were reviewed retrospectively. They were a subgroup of 756 patients admitted to hospitals during the same period. The average endotracheal/tracheostomy cannulation time was 3 weeks/12 weeks (range 2 to 4 weeks/8 to 14 weeks). Average age was 76 years (range, 34 to 81). Underlying diseases included COPD, postcoronary artery bypass graft surgery, postpneumonectomy, severe pneumonia, acute lung injury, and ischemic heart disease. All 37 patients who initially failed to wean had difficulty in breathing and developed intermittent high peak airway pressures either early or during the weaning process or just on being ventilated. The insertion of a longer tracheal tube bypassed the obstruction, reestablished the airway, decreased peak airway pressures, and allowed the patient to breathe more easily. The obstruction was confirmed on bronchoscopy. Treatment consisted of either placement of a longer tracheal tube (34 of 37 patients) or placement of a tracheal stent. All but two of the patients (5.4%) were able to be weaned within a week. The two patients who still failed to be weaned were subsequently diagnosed as having amyotrophic lateral sclerosis. Tracheal obstruction in patients requiring prolonged mechanical ventilation prevented weaning. Reestablishment of the airway with a longer tracheal tube or tracheal stent allowed most of the patients to be weaned.


Granulomatous Mastitis in a Transgender Patient.
Granulomatous mastitis is a rare and benign inflammatory condition of the breast most commonly affecting women of child-bearing age as well as patients on oral contraceptives. This condition is important to identify due to its diagnostic mimicry of malicious entities such as breast carcinoma. Clinical and radiological findings are nonspecific and may overlap with breast carcinomas, thus pathologic confirmation is often necessary for definitive diagnosis. Although cases of granulomatous mastitis have been described in cisgender females, there have been no reported cases in the transgender patient, a growing patient population with few imaging guidelines. Transgender patients are at risk of developing this breast entity due to the use of long-term hormone treatments or presence of residual breast tissue. A trial of antibiotics or steroids may be administered. However, surgical treatment is often necessary in recurrent or refractory cases.


Differential roles of WNK4 in regulation of NCC in vivo.
The Na+-Cl- cotransporter (NCC) in distal convoluted tubule (DCT) plays important roles in renal NaCl reabsorption. The current hypothesis for the mechanism of regulation of NCC focuses on WNK4 and intracellular Cl- concentration ([Cl-]i). WNK kinases bind Cl-, and Cl- binding decreases the catalytic activity. It is believed that hypokalemia under low K+ intake decreases [Cl-]i to activate WNK4, which thereby phosphorylates and stimulates NCC through activation of SPAK. However, increased NCC activity and apical NaCl entry would mitigate the fall in [Cl-]i. Whether [Cl-]i in DCT under low-K+ diet is sufficiently low to activate WNK4 is unknown. Furthermore, increased luminal NaCl delivery also stimulates NCC and causes upregulation of the transporter. Unlike low K+ intake, increased luminal NaCl delivery would tend to increase [Cl-]i. Thus we investigated the role of WNK4 and [Cl-]i in regulating NCC. We generated Wnk4-knockout mice and examined regulation of NCC by low K+ intake and by increased luminal NaCl delivery in knockout (KO) and wild-type mice. Wnk4-KO mice have marked reduction in the abundance, phosphorylation, and functional activity of NCC vs. wild type. Low K+ intake increases NCC phosphorylation and functional activity in wild-type mice, but not in Wnk4-KO mice. Increased luminal NaCl delivery similarly upregulates NCC, which, contrary to low K+ intake, is not abolished in Wnk4-KO mice. The results reveal that modulation of WNK4 activity by [Cl-]i is not the sole mechanism for regulating NCC. Increased luminal NaCl delivery upregulates NCC via yet unknown mechanism(s) that may override inhibition of WNK4 by high [Cl-]i.


The experimental validation of free fat grafts in thoracic surgery.
We evaluated the viability of free fat grafts in the thoracic cavity using 3-month old male swine (n = 2). After left caudal lobectomy, 1-3 g of subcutaneous fat tissue harvested via the thoracotomy site was implanted in the chest cavity. At re-thoracotomy 6 weeks after implantation, all of the implanted fat grafts (n = 15) were found to have closely adhered to the parietal pleura and visceral pleura. There was a significant decrease by ∼30% in the weight of the fat grafts after implantation. Regardless of the weight loss, the implanted fat graft showed normal structuring without scar formation in the central area. Our results may suggest that free fat pads, which weighed up to 3 g, were successfully cultured in the thoracic cavity until the implanted tissues integrated into the surrounding tissues. Therefore, the free fat pad can be used as a biomaterial for some purposes in thoracic surgery.


Rate of forearm bone loss is associated with an increased risk of fracture independently of bone mass in postmenopausal women: the OFELY study.
BMD is a major determinant of the risk of fragility fractures, but the role of the rate of postmenopausal bone loss is still unclear. In 671 postmenopausal women from the OFELY cohort, we found that the rate of bone loss was significantly associated with fracture risk independently of other well-known predictors including BMD and previous fractures. The level of BMD is a major determinant of the risk of fragility fractures, but the role of the rate of postmenopausal bone loss is still unclear. In the OFELY study, we analyzed the risk of fracture in 671 postmenopausal women (mean age, 62.2 +/- 9 years), according to the rate of bone loss. BMD was measured annually by DXA at the forearm, with a mean number of measurements of 10.3 +/- 2.6. Peripheral fractures, all confirmed by radiographs, were prospectively registered, and vertebral fractures were evaluated with spine radiographs every 4 years. During a median (interquartile range [IQ]) of 11.2 years (11-12.3 years) of follow-up, 183 incident fragility fractures including 53 vertebral and 130 nonvertebral fractures were recorded in 134 women. The annual median +/- IQ rate of bone loss, calculated from the slope, was -0.30 +/- 0.76% at the mid-radius, -0.55 +/- 0.79% at the distal radius, and -0.40 +/- 0.96% at the ultradistal radius. Women with incident fracture had a rate of bone loss (before fracture) higher by 38-53% than those without fracture (p = 0.0003-0.016). Using multivariate Cox regression models, we found that bone loss in the highest tertile at the mid-radius, distal radius, and ultradistal radius was associated with a significant increased risk of all fractures with an hazard ratio from 1.45 to 1.70 (p = 0.02 to p = 0.009 after adjusting for age, previous fractures, maternal history of fracture, physical activity, grip strength, falls, and baseline BMD). The rate of bone loss in postmenopausal women is significantly associated with fracture risk independently of other well-known predictors such as BMD and history of fractures.


Practitioners, postnatal depression, and translation: An investigation into the representation of Bangladeshi mothers in the East End.
This paper is based on research that investigated the personal, localised and institutional representations of the emotional experiences of Bangladeshi mothers in Tower Hamlets, London. The research was conducted during 2003 and 2004. Whilst the London borough of Tower Hamlets is not deprived by global standards, within the UK the borough ranks very low on certain socio-economic indicators. Simultaneously, the 'East End' can still conjure up images of heart-warming kinship and of a place that welcomes migrants. These, and other contradictory depictions, are used by the people who both live and work in the borough. Through the investigation of the narratives of those who work with Bangladeshi mothers, this paper explores the role of culture as presented in both self-conscious and implicit terms. Further to this, it examines what claims are based on these conceptions. This analysis demonstrates that institutions are not neutral spaces in which identities and representations of experience are produced, but in fact shape the very nature of these identities and representations. As focal points this paper chooses health and motherhood as loci where personal experience, social institutions and notions of 'culture' all intersect. To stress only that the experience of motherhood is undeniably a feature of shared humanity would be to ignore the fact that reproduction is also culturally mediated and reconstructed. Through discussions such as those concerning the nature of 'postnatal depression', depicted as having both universal and culturally specific elements, debates around ethnicity and class are also brought into sharper focus.


Review of the decontamination of aflatoxins by ammoniation: current status and regulation.
Ammoniation of corn, peanuts, cottonseed, and meals to alter the toxic and carcinogenic effects of aflatoxin contamination has been the subject of intense research effort by scientists in various government agencies and universities, both in the United States and abroad. Results of these studies have been well documented over the last 20 years. Engineers have devised workable systems of treatment of whole seeds, kernels, or meals; chemists have identified and characterized products formed from the reaction of aflatoxin B1 with ammonia with and without a meal matrix; biochemists have studied the biological effects of these compounds in model systems; and nutritionists have studied animal responses to rations containing ammoniated or non-ammoniated components. This review describes these studies. Results demonstrate overwhelming support for the efficacy and safety of ammoniation as a practical solution to aflatoxin detoxification in animal feeds.


Study on pathogenic genes of dwarfism disease by next-generation sequencing.
There are many factors that lead to dwarfism, and the mechanism has not yet been elucidated. Next-generation sequencing may identify candidate-related gene mutations, which may clarify the molecular cause. To analyze genetic variation by using a constructed panel related to dwarfism by utilizing next-generation sequencing platform sequencing analysis to screen candidate-related gene mutations. Physical and laboratory characteristics, including clinical examination, growth hormone drug challenge test, serum insulin-like growth factor-1 (IGF-1), IGF binding protein 3, other related tests, imaging examination, and chromosome karyotyping, were analyzed. Next-generation sequencing was performed to analyze pathogenicity variability. In the 39 dwarfism patients, 10 had pathogenicity variability. Gene variation was found in the OBSL1, SLC26A2, PTPN11, COL27AI, HDAC6, CUL7, FGFR3, DYNC2H1, GH1, and ATP7B genes. Of the 10 patients with pathogenicity variability, the related physical characteristics included double breast development and growth hormone deficiency, enuresis and indirect inguinal hernia on the left, two finger distance of 70.2 cm, head circumference of 49.2 cm, ischium/lower body length of 1.8 cm, weak limb muscles, and partial growth hormone deficiency. After 6 mo of growth hormone therapy, the concentrations of IGF-1 and IGF binding protein 3 increased from 215.2 ± 170.3 to 285.0 ± 166.0 and 3.9 ± 1.4 to 4.2 ± 1.1, respectively. OBSL1, SLC26A2, PTPN11, COL27AI, HDAC6, CUL7, FGFR3, DYNC2H1, GH1, and ATP7B genes may be related to the incidence of dwarfism, and more research needs to be performed to elucidate the mechanism.


The Violence Prevention Community Meeting: A Multi-Site Study.
The Violence Prevention Community Meeting (VPCM) is a specialized form of community meeting in which avoiding violence and promoting non-violent problem solving and interpersonal civility are focal points. A nationwide study to assess the VPCM as an effective intervention to reduce workplace violence was undertaken. Seven acute locked psychiatric units of the Veterans Health Administration (VHA) throughout the United States participated in the study. All patients and all staff on the seven in-patient locked psychiatry units participated in the intervention (VPCM) or as a control (treatment as usual). The study was 21weeks at each site. The three time periods were pre-treatment weeks 1-3, treatment weeks 4-18, and post-treatment weeks 19-21. The VPCM was conducted during the treatment weeks. Overall rates of aggression declined by 0.6% (95% CI: -5.6%, 6.5%; nonsignificant) per week in the intervention hospitals and by 5.1% (95% CI: 0.4%, 9.6%; significant) per week for the control hospitals. Aggression decreased for both the intervention and control hospitals which could be due to enrollment in a research study and thus being more aware of their ability to address workplace violence at their site.


The safety of a nitric oxide inhalation system with high frequency oscillatory ventilation.
Nitric oxide (NO) inhalation and high frequency oscillatory ventilation (HFOV) has been indicated in infants with severe respiratory failure. The purpose of the present study was to evaluate the safety of an NO inhalation system with HFOV in terms of nitrogen dioxide (NO2) production. The NO inhalation system consisted of a high frequency oscillatory ventilator, a neonatal circuit and a test lung. The NO concentration was changed from 0 to 19 p.p.m. At each level of NO, the oxygen (O2) concentration was changed from 21 to 100%. The NO and NO2 concentrations were measured with a chemiluminescence analyzer using a molybdenum converter. The NO2 concentration was increased when either the O2 or the NO concentration was increased. The interposition of the endotracheal tubes increased NO2 concentrations at 4 p.p.m. NO. The high stroke volume and high mean airway pressure produced a significant increase in NO2 production at 4 p.p.m. NO. The increase in NO2 production was prevented by placing a one-way valve at the joint of the NO gas line to the inspired limb. It was concluded that the NO inhalation system with HFOV can be safely used when a one-way valve is placed at the joint of the NO gas line to the inspired limb and when inhaled NO is at a relatively low concentration.