Factors influencing the selection of general internal medicine fellowship programs: a national survey.
Although criteria are available to guide the selection of general internal medicine (GIM) fellowship programs, the factors actually used in this process are unclear. Using a survey of current GIM fellows, we determined that most received information from their residency advisors, and many viewed them as the most important source of fellowship information. Program location was the top selection factor for fellows, followed by research opportunities, availability of a mentor, and the reputation of the program. This information may be useful to both fellowship candidates as an additional selection guide and to program directors seeking to best structure and market their fellowships.


Recent Advances in Biosensing With Photonic Crystal Surfaces: A Review.
Photonic crystal surfaces that are designed to function as wavelength-selective optical resonators have become a widely adopted platform for label-free biosensing, and for enhancement of the output of photon-emitting tags used throughout life science research and in vitro diagnostics. While some applications, such as analysis of drug-protein interactions, require extremely high resolution and the ability to accurately correct for measurement artifacts, others require sensitivity that is high enough for detection of disease biomarkers in serum with concentrations less than 1 pg/ml. As the analysis of cells becomes increasingly important for studying the behavior of stem cells, cancer cells, and biofilms under a variety of conditions, approaches that enable high resolution imaging of live cells without cytotoxic stains or photobleachable fluorescent dyes are providing new tools to biologists who seek to observe individual cells over extended time periods. This paper will review several recent advances in photonic crystal biosensor detection instrumentation and device structures that are being applied towards direct detection of small molecules in the context of high throughput drug screening, photonic crystal fluorescence enhancement as utilized for high sensitivity multiplexed cancer biomarker detection, and label-free high resolution imaging of cells and individual nanoparticles as a new tool for life science research and single-molecule diagnostics.


The Formal Language and Design Principles of Autonomous DNA Walker Circuits.
Simple computation can be performed using the interactions between single-stranded molecules of DNA. These interactions are typically toehold-mediated strand displacement reactions in a well-mixed solution. We demonstrate that a DNA circuit with tethered reactants is a distributed system and show how it can be described as a stochastic Petri net. The system can be verified by mapping the Petri net onto a continuous-time Markov chain, which can also be used to find an optimal design for the circuit. This theoretical machinery can be applied to create software that automatically designs a DNA circuit, linking an abstract propositional formula to a physical DNA computation system that is capable of evaluating it. We conclude by introducing example mechanisms that can implement such circuits experimentally and discuss their individual strengths and weaknesses.


The catecholamine carrier of bovine chromaffin granules. Form of the bound amine.
The binding of [2-3H]dihydrotetrabenazine (2-hydroxy-3-isobutyl-9, 10-dimethoxy-1,2,3,-4,6,7-hexahydro-11bH-benzo [a]quinolizine), a tetrabenazine derivative which binds to the catecholamine carrier of chromaffin granule membranes, has been studied as a function of the pH. The number of binding sites was constant from pH 6.5 to pH 9.0, whereas the KD decreased to a minimal plateau value, obtained at pH values higher than 7.5, the drug pKa. The pH dependency of the displacement of [3H]dihydrotetrabenazine by noradrenaline was also investigated. Noradrenaline KD values derived from displacement experiments decreased logarithmically when the pH increased from 6.5 to 8.5, i.e., for pH values lower than the pKa of noradrenaline. These pharmacological data support our previous hypothesis based on kinetic data [Scherman and Henry, Eur. J. Biochem. 116:535-539 (1981)] that the monoamine carrier of the chromaffin granule membrane binds and transports neutral amines, a form of low abundancy at physiological pH but for which it has a high affinity.


Berberine accelerated wound healing by restoring TrxR1/JNK in diabetes.
The high disability, mortality and morbidity of diabetic ulcers make it urgent to explore effective strategies for diabetic wound repair. TrxR1 plays a vital role in regulating redox homeostasis in various pathologies. In the present study, the effect of berberine (BBR) on diabetic wounds was investigated in streptozotocin (STZ)-induced diabetic rats and a high glucose (HG)-induced cell model, and the mechanism of BBR on TrxR1 was elucidated. BBR treatment remarkably accelerated wound healing and enhanced extracellular matrix (ECM) synthesis and significantly inhibited HG-induced HaCaT cell damage. Further analysis indicated that BBR activated TrxR1, suppressed its downstream JNK signaling, thereby inhibiting oxidative stress and apoptosis, promoted cell proliferation, down-regulated matrix metalloproteinase (MMP) 9 (MMP9) and up-regulated transforming growth factor-β1 (TGF-β1) and tissue inhibitors of MMP 1 (TIMP1), resulting in accelerated wound healing. Importantly, the enhancement of BBR on wound repair was further abolished by TrxR1 inhibitor. Moreover, in diabetic wounds induced by a combination of STZ injection and high-fat diet, BBR significantly increased wound closure rate and TrxR1 expression, and this was reversed by TrxR1 inhibitor. These data indicated that topical BBR treatment accelerated diabetic wound healing by activating TrxR1. Targeting TrxR1 may be a novel, effective strategy for restoring redox homeostasis and promoting diabetic wound healing.


In vitro evaluation of the marginal degradation of dental composites under simulated occlusal loading.
Our objective was to use an in vitro oral wear simulator to compare the susceptibility to marginal breakdown of different classes of dental composites. Two microfill composites (Silux Plus, 3M and Heliomolar, Vivadent), two minifills (Z100, 3M and Herculite, Kerr) and two midifills (Fulfil, Caulk and Clearfil, Kuraray) were placed in two increments (40 s cure) into class I cavities (5 x 3.5 x 2 mm3 deep) cut into the facial enamel surfaces of bovine incisors treated with an adhesive (Scotchbond MP, 3M). The restored teeth were aged 1 day in water, mounted in the OHSU oral wear simulator, covered with a slurry of poppy seeds/PMMA beads and subjected to 50 K cycles of wear against an enamel stylus [J.R. Condon, J.L. Ferracane, Evaluation of composite wear with a new multi-mode oral wear simulator, Dent. Mater. 12 (1996) 218-226). The specimens (n = 10) were positioned to produce abrasive wear (load = 20 N] across one margin and attrition wear (load = 70 N) across the second margin. Volume loss of material (mm3 x 1000) was estimated from 10 profilometric tracings perpendicular to the attrition margin, and then differentiated into composite and enamel degradation. Fracture toughness of the composites was measured in bending with the single-edge notch technique. Results were compared with ANOVA and Tukey's test at p < 0.05. Significant wear of the composite was produced at the attrition margin. Enamel degradation at the margin paralleled the composite results. The microfills, and to a lesser extent the minifills, showed more marginal breakdown than the midifill composites. Marginal breakdown shows an excellent inverse correlation with fracture toughness for these composites. These results are in general agreement with clinical studies showing greater marginal degradation for microfill composites and suggest that the OHSU oral wear simulator may be a useful adjunct for the study of the marginal degradation of dental composites.


Improved flow cytometric detection of HLA alloantibodies using pronase: potential implications in renal transplantation.
Flow cytomeric crossmatch (FCXM) has grown in popularity and has become the "standard of practice" in many programs. Although FCXM is the most sensitive method for detecting alloantibody, the B cell FCXM has been problematic. Difficulties with the B cell FCXMs have been centered around high nonspecific fluorescence background owing to Fc-receptors present on the B cells and autoantibodies. To improve the specificity and sensitivity of the B cell FCXM, we utilized the proteolytic enzyme pronase to remove Fc receptors from lymphocytes before their use in FCXM. Lymphocytes isolated from peripheral blood, spleen, or lymph nodes were treated with pronase and then used in a three-color FCXM. A total of 167 T- and B cell FCXMs using pronase-treated and untreated cells were performed. Testing used serial dilutions of HLA allosera (22 class I and 6 class II), with the titer of each antibody at one dilution past the titer at which the complement-mediated cytotoxicity anti-human globulin crossmatch became negative. After pronase treatment, the actual channel values of the negative control in both T cell and B cell FCXMs declined from 78+/-10 to 57+/-4 (P<0.05) and 107+/-11 to 49+/-3 (P<0.00001), respectively. Pronase treatment resulted in improved sensitivity of the T and B cell FCXM in detecting class I antibody by 20% and 80%, respectively. In no instance was a false-positive reaction observed. In this study, pronase treatment improved the specificity of B cell FCXM for detecting class II antibodies from 75% to 100% (P=0.03). In no instance was a false-negative reaction recorded. Lastly, on the basis of these observations we re-evaluated three primary transplant recipients who lost their allografts because of accelerated rejection. One of the patients was transplanted across negative T and B cell FCXM, whereas the other two patients were transplanted across a positive T cell, but negative B cell, FCXM. After pronase treatment, T and B cell FCXMs of each patient became strongly positive, and donor-specific anti-HLA class I antibody was identi. fied in each case. Utilization of pronase-treated lymphocytes improves both the sensitivity and specificity of the FCXM.


Carbon allocation under light and nitrogen resource gradients in two model marine phytoplankton(1).
Marine phytoplankton have conserved elemental stoichiometry, but there can be significant deviations from this Redfield ratio. Moreover, phytoplankton allocate reduced carbon (C) to different biochemical pools based on nutritional status and light availability, adding complexity to this relationship. This allocation influences physiology, ecology, and biogeochemistry. Here, we present results on the physiological and biochemical properties of two evolutionarily distinct model marine phytoplankton, a diatom (cf. Staurosira sp. Ehrenberg) and a chlorophyte (Chlorella sp. M. Beijerinck) grown under light and nitrogen resource gradients to characterize how carbon is allocated under different energy and substrate conditions. We found that nitrogen (N)-replete growth rate increased monotonically with light until it reached a threshold intensity (~200 μmol photons · m(-2) · s(-1) ). For Chlorella sp., the nitrogen quota (pg · μm(-3) ) was greatest below this threshold, beyond which it was reduced by the effect of N-stress, while for Staurosira sp. there was no trend. Both species maintained constant maximum quantum yield of photosynthesis (mol C · mol photons(-1) ) over the range of light and N-gradients studied (although each species used different photophysiological strategies). In both species, C:chl a (g · g(-1) ) increased as a function of light and N-stress, while C:N (mol · mol(-1) ) and relative neutral lipid:C (rel. lipid · g(-1) ) were most strongly influenced by N-stress above the threshold light intensity. These results demonstrated that the interaction of substrate (N-availability) and energy gradients influenced C-allocation, and that general patterns of biochemical responses may be conserved among phytoplankton; they provided a framework for predicting phytoplankton biochemical composition in ecological, biogeochemical, or biotechnological applications.


Chiropractic management of migraine without aura. A case study.
To assess the response of a patient with chronic migraines to a short program of chiropractic care (diversified technique). The study was run over a 13 week period with chiropractic spinal manipulative therapy (CSMT) on a once weekly schedule for 5 weeks, followed by an 8 week re-evaluation. To measure the effect of treatment, a previously reported diary system was used which noted the intensity of a range of symptoms that are recorded following each migraine episode. The results attained showed there was a marked improvement in the migraine symptoms following the chiropractic care. The patient reported an improvement in frequency, intensity, duration and use of medication. These findings appear to also confirm other evidence which documented similar changes following a large randomised controlled trial of chiropractic treatment of migraine. The case is presented as further support for CSMT in the treatment of migraine. The outcome of this case is also discussed in relation to recent research that concludes that CSMT is a very effective treatment for some people with non-neuromusculoskeletal conditions. It now appears clear that chiropractic care may be used to assist patients with migraine. Research is currently being undertaken to investigate the potential mechanisms of chiropractic in the treatment of migraine. This research should also assess what (if any) prognostic signs can be identified to assist practitioners making a more informed decision on the treatment of choice for migraine.


Pre-medical majors in the humanities and social sciences: impact on communication skills and specialty choice.
Medical school admissions committees use a variety of criteria to determine which candidates to admit to their programmes. Effective communication is increasingly considered a key requisite to the practice of effective medicine. Medical students with pre-medical backgrounds in the humanities and social sciences may be more likely to acquire skills relevant to patient-centred communication, either prior to or during medical school. The purpose of this study was to investigate the relationship between pre-medical backgrounds in the humanities and social sciences and outcomes in medical school, including in communication and interpersonal skills (CIS), licensure examination results and postgraduate specialty choice (primary care versus non-primary care specialties). The American Medical College Application Service database was used to identify pre-medical college majors, demographic characteristics, Medical College Admission Test scores and college grade point averages for medical students at a large, midwestern medical school. Data were obtained for 465 medical students across three cohorts (classes of 2014-2016). Correlation and regression analyses were used to examine relationships between pre-medical background, performance on graduation competency examination standardised patient encounter CIS scores and on United States Medical Licensing Examination (USMLE) Step 1 and Step 2 Clinical Knowledge scores, and postgraduate specialty choice. Graduating medical students with pre-medical humanities or social sciences majors performed significantly better in terms of CIS than those with natural science majors (Cohen's d = 0.28, p = 0.011). There were no significant associations between pre-medical majors and USMLE Step 1 and Step 2 Clinical Knowledge scores or postgraduate specialty choice. These results suggest that considering humanistic factors as part of admissions criteria may promote the selection and training of physicians with good communication skills.


Cultured muscle cells display defects of mitochondrial myopathy ameliorated by anti-oxidants.
The mitochondrial DNA A3243G mutation causes neuromuscular disease. To investigate the muscle-specific pathophysiology of mitochondrial disease, rhabdomyosarcoma transmitochondrial hybrid cells (cybrids) were generated that retain the capacity to differentiate to myotubes. In some cases, striated muscle-like fibres were formed after innervation with rat embryonic spinal cord. Myotubes carrying A3243G mtDNA produced more reactive oxygen species than controls, and had altered glutathione homeostasis. Moreover, A3243G mutant myotubes showed evidence of abnormal mitochondrial distribution, which was associated with down-regulation of three genes involved in mitochondrial morphology, Mfn1, Mfn2 and DRP1. Electron microscopy revealed mitochondria with ultrastructural abnormalities and paracrystalline inclusions. All these features were ameliorated by anti-oxidant treatment, with the exception of the paracrystalline inclusions. These data suggest that rhabdomyosarcoma cybrids are a valid cellular model for studying muscle-specific features of mitochondrial disease and that excess reactive oxygen species production is a significant contributor to mitochondrial dysfunction, which is amenable to anti-oxidant therapy.


Microplastics and their environmental effects.
Microplastics (MPs) are acknowledged as emerging contaminants that pose a substantial threat to the environment. The adverse impacts of MP pollution extend across marine, freshwater, and terrestrial ecosystems, covering regions from the Tropics to the Poles. Although our comprehension of MP behavior has progressed in recent years, it is still difficult to predict exposure hotspots or exposure scenarios. Despite a noteworthy increase in data concerning MP occurrence in different environmental compartments and species, there is a noticeable scarcity of experimental data on MP uptake, accumulation, and effects. This Virtual Special Issue (VSI) received a total of 19 contributions from 11 countries, with a significant majority originating from Italy, India, Spain, and China. These contributions were categorized into three main themes: the occurrence and effects of MPs on aquatic and terrestrial organisms, the presence of chemical additives in plastics, and review articles summarizing previously published research on MPs.


Atmosphere-surface interactions on Mars: delta 17O measurements of carbonate from ALH 84001.
Oxygen isotope measurements of carbonate from martian meteorite ALH 84001 (delta18O = 18.3 +/- 0.4 per mil, delta17O = 10.3 +/- 0.2 per mil, and Delta17O = 0.8 +/- 0.05 per mil) are fractionated with respect to those of silicate minerals. These measurements support the existence of two oxygen isotope reservoirs (the atmosphere and the silicate planet) on Mars at the time of carbonate growth. The cause of the atmospheric oxygen isotope anomaly may be exchange between CO2 and O(1D) produced by the photodecomposition of ozone. Atmospheric oxygen isotope compositions may be transferred to carbonate minerals by CO2-H2O exchange and mineral growth. A sink of 17O-depleted oxygen, as required by mass balance, may exist in the planetary regolith.


Imaging experimental osteomyelitis using radiolabeled liposomes.
We evaluated radiolabeled liposomes (liposomes labeled both with 99mTc and 111In) for the early detection of osteomyelitis in an experimental model. Liposomes, containing 5% polyethylene glycol-distearoyl phosphatidylethanolamine with encapsulated glutathione and deferoxamine, were prepared and labeled with 99mTc and 111In by a previously described method. Acute osteomyelitis was induced in male New Zealand rabbits by intramedullary injection of sodium-morrhuate and Staphylococcus aureus in the tibial bone marrow. Serial imaging studies, consisting of radiolabeled liposome imaging (2-4 mCi 99mTc and 75-125 microCi 111In), 99mTc-methylene diphosphonate (MDP) (3-5 mCi) and 67Ga-citrate (500 microCi), were performed starting at the third day after injection. Each radionuclide study was separated by at least 2 days. The animals also underwent radiography of the lower extremities. The animals were then killed and the infected tibia was excised for histopathology. For interpreting relative efficacy of individual radiopharmaceuticals, only animals showing positive histopathological findings (n = 9) were considered. Radiographs (Days 12, 13) were conclusive for osteomyelitis in only 3 rabbits. Radiolabeled liposome imaging (Days 4-6) showed positivity in 8 cases and was equivocal in 1. Though the lesion could be delineated as early as 8 hr postinjection in the 99MTc window, the best target-to-nontarget ratio (T/NT) of 1.86 +/- 0.19 was obtained at 48 hr in the 111In window. Three-phase 99mTc-MDP scan (Day 7) was positive in only 5 rabbits with 3 hr T/NT of 1.6 +/- 0.23. Galium-67-citrate images (Days 9-11) were positive in 8 cases and equivocal in 1, the mean 48 hr T/NT being 1.74 +/- 0.24. These results show liposomes are better than 99mTc-MDP for imaging bone infection. Given the early localization and better quality of the images, radiolabeled liposomes also exhibited advantages over 67Ga-citrate for detection of acute osteomyelitis.


[Neurophysiological bases of vestibular training].
Occupation-oriented vestibular selection is based on the two principles: selection of vestibular-resistant subjects, and increase of vestibular tolerance through training. The latter implies inherited ability of the central nervous system to attenuate vestibular reactions. The review surveys experimental data concerning attenuation (habituation) of vestibular reactions as a result of prolonged or reiterative excitation of labyrinthine receptors. The review discusses peculiar features of the development, stability and transfer of habituation. It gives data on disturbed habituation as a result of an exposure to stress-effects (hypokinesia, hypoxia, hypothermia) and certain drugs. The phenomenon of vestibular habituation is interpreted in terms of Sokolov's concept of the stimulus nervous model.


Effect of 3 Euthanasia Methods on Serum Yield and Serum Cortisol Concentration in Zebrafish (Danio rerio).
Zebrafish are an important model in neuroscience and developmental biology and are also an emerging model in hematology and immunology. Little information is available for zebrafish regarding the physiologic impact of different euthanasia methods and whether a chosen method of euthanasia can impact serum yield. These parameters could impact the choice of euthanasia method for a study. To that end, the current study compared 3 methods of adult zebrafish euthanasia and their effects on 3 distinct criteria; time to loss of opercular movement, volume of serum obtained, and serum cortisol concentration. Blood was collected using a postmortem tail amputation and centrifugation blood collection technique. Time to loss of opercular movement differed significantly among euthanasia methods, with animals undergoing rapid chilling displaying the shortest time (mean Rapid Chilling: 40 s; Benzocaine: 86 s; MS222: 96 s). All methods of euthanasia resulted in a comparable average serum yield (Rapid Chilling = 7.5 μL; Benzocaine = 8.5 μL; MS222 = 7.5 μL per fish). None of the euthanasia methods tested resulted in average cortisol concentrations above the reported physiologic range. Although no significant differences were observed in serum yield or serum cortisol concentration, rapid chilling remains the preferred method for painless, humane euthanasia.


Effects of LHRH, FSH and activin A on follistatin secretion from cultured rat anterior pituitary cells.
We demonstrated the release of follistatin, an activin-binding protein, from cultured rat anterior pituitary cells by measuring immunoreactive (ir-) follistatin in a specific immunoradiometric assay. Ir-follistatin release gradually increased in cultures over 1-18 days and reached its maximal level at 12-15 days of incubation. The basal ir-follistatin levels in the culture media increased about 3- (P < 0.01) and 5-fold (P < 0.001) in 2 and 10% fetal calf serum for 6 days, respectively. LHRH and activin A caused an approximately 2.0- (P < 0.05) and 1.8-fold (P < 0.05) rise in ir-follistatin release, respectively, in contrast to the lack of significant FSH effects. The culture medium condensed on sulfate-cellulofine gel was resolved by polyacrylamide gel electrophoresis and blotted with anti-follistatin polyclonal antibody, resulting in at least three protein bands ranging from 35 to 50 kDa under non-reducing conditions. These results indicated that follistatin is produced in anterior pituitary cells and that its secretion is regulated at least in part by LHRH and activin, implying an autocrine/paracrine role of activin and follistatin in the pituitary.


Successful resuscitation of cardiac arrest caused by CO2 embolism with intra-aortic injection of epinephrine during off-pump coronary bypass surgery -a case report-.
Although compressed gas (CO2) blowers have been used safely to aid accurate grafting during off-pump coronary bypass surgery, hemodynamic collapse due to gas embolism into the right coronary artery may occur. Supportive measures to facilitate gas clearance by increasing the coronary perfusion pressure have been reported to be successful in restoring hemodynamic stability. However, right ventricular dysfunction and atrioventricular nodal ischemia may hinder effective systemic delivery of the vasoactive medications, even when performing resuscitative measures such as direct cardiac massage. We herein report a case of cardiac arrest that was caused by a right coronary gas embolism and that could not be restored by cardiac resuscitation. When supportive measures fail, direct aortic injection of epinephrine to increase the coronary perfusion pressure can be attempted before initiating cardiopulmonary bypass, and this approach may be life-saving in situations that limit systemic drug delivery from the venous side despite the performance of direct cardiac massage.


Dallas UtErus Transplant Study: Early Outcomes and Complications of Robot-assisted Hysterectomy for Living Uterus Donors.
Uterus transplantation is a treatment for absolute uterine infertility and can be performed with living and deceased donors. Given the safety and increased utilization of robotic assistance with other gynecologic and transplant donor operations, we adopted a robot-assisted approach to donor hysterectomy. This study compared early outcomes and morbidity of the robot-assisted approach to donor hysterectomy with the traditionally performed open approach and addressed whether the robot-assisted approach is safe and offers advantages for the donor. Our institution has performed 18 living donor hysterectomies for uterus transplantation. This retrospective review compared the last 5 cases utilizing a robot-assisted technique and vaginal extraction of the uterus graft with the first 13 cases performed with an open laparotomy technique. Demographic, intraoperative, and postoperative data were examined. There were no differences between the robot-assisted and the open living donor group with respect to age, body mass index, or gynecological history. Although the median operative time was shorter for the open approach (6.27 versus 10.46 h), the donors' median estimated blood loss, length of hospital stay, and length of sick leave were less with the robot-assisted approach. There was no conversion to open hysterectomy in the robot-assisted cases, and the incidence of complications was similar between the 2 groups. There was no difference in early graft function. These preliminary results show that robot-assisted living donor hysterectomy is feasible and safe for the donors; it allows a faster postoperative recovery and the same early graft function.


[Importance of a thymus dysfunction in the pathophysiology of type 1 diabetes].
The autoimmune nature of the diabetogenic process and the major contribution of T lymphocytes stand now beyond any doubt. However, despite the identification of the three major type 1-diabetes-related autoantigens (insulin, GAD65 and phosphatase IA-2), the origin of this immune dysregulation still remains unknown. More and more evidence supports a thymic dysfunction in the establishment of central self-tolerance to the insulin family as a crucial factor in the development of the autoimmune response selective of pancreatic insulin-secreting islet beta cells. All the genes of the insulin family (INS, IGF1 and IGF2) are expressed in the thymus network. However, IGF-2 is the dominant member of this family first encountered by T cells in the thymus, and only IGFs control early T-cell differentiation. IGF2 transcription is defective in the thymus in one animal model of type 1 diabetes, the Bio-Breeding (BB) rat. The sequence B9-23, one dominant autoantigen of insulin, and the homologous sequence B11-25 derived from IGF-2 exibit the same affinity and fully compete for binding to DQ8, one class-II major histocompatibility complex (MHC-II) conferring major genetic susceptibility to type 1 diabetes. Compared to insulin B9-23, the presentation of IGF-2 B11-25 to peripheral mononuclear cells (PBMCs) isolated from type 1 diabetic DQ8+ adolescents elicits a regulatory/tolerogenic cytokine profile (*IL-10, *IL-10/IFN-g, *IL-4). Thus, administration of IGF-2 derived self-antigen(s) might constitute a novel form of vaccine/immunotherapy combining both an antagonism for the site of presentation of a susceptible MHC allele, as well as a downstream tolerogenic/regulatory immune response.


[Operative treatment of hallux valgus].
A new method of operative treatment for hallux valgus consists in a derotational osteotomy of the first metatarsal bone and adductorotenotomy, that allows a correction of the deformity without an operation on the first metatarsophalangeal joint. A total of 67 patients were operated upon (81 operations). Late results were followed up in 48 patients (59 operations). Excellent and good results after the operation were noted in 47, satisfactory-in 10 and poor-in 2 observations. The operation is thought to be indicated in marked deformities.


Removal of pharmaceuticals from water: using liquid-core microcapsules as a novel approach.
In recent years ever-increasing amounts of pharmaceuticals are being detected in the aquatic environment and in some cases, they have even been discovered in drinking water. Their presence is attributed mainly to the inability of sewage treatment plants to adequately remove these compounds from the sewage influent. The aim of this study was to investigate the feasibility, kinetics and efficiency of using liquid-core microcapsules as a novel methodology, termed capsular perstraction, to remove seven pharmaceuticals commonly found in the environment, from water. The process involves the envelopment of pre-selected organic solvents within a porous hydrogel membrane to form liquid-core microcapsules, which can be used to extract a large range of compounds. Results indicate that this novel approach is capable of extracting the seven chosen compounds rapidly and with a variable efficiency. The simultaneous use of both dibutyl sebacate and oleic acid liquid-core microcapsules at a liquid volume ratio of only 4% (v/v) resulted in the following extractions within 50min of capsule addition to contaminated water: furosemide 15%; clofibric acid 19%; sulfamethoxazole 22%; carbamazepine 54%; warfarin 80%; metoprolol 90% and diclofenac 100%. The effects of different agitation rates, microcapsule size and membrane thickness on the rate of mass transfer of warfarin into the liquid-core (dibutyl sebacate) of microcapsules was also examined. Results showed that the main rate-limiting step to mass transfer was due to the stagnant organic film (microcapsule size) within the core of the microcapsules. A volumetric mass transfer coefficient of 2.28x10(-6)m/s was obtained for the smallest microcapsules, which was nearly 4-fold higher compared to the value (0.6x10(-6)m/s) obtained for the largest microcapsules used in this study. Even with this resistance liquid-core microcapsules are still capable of the rapid extraction of the tested compounds and may provide a platform for the safe disposal of the pharmaceuticals after removal.


Defining the short-term disease recurrence after loop electrosurgical excision procedure (LEEP).
The goal of cervical cancer screening is to identify dysplastic lesions for subsequent excision in order to prevent invasive disease. There is clinical equipoise, on how to best follow women for disease surveillance after treatment with some Canadian provinces exclusively performing colposcopy and some utilizing Human Papilloma Virus (HPV) testing in addition to cervical cytology. Loop Electrosurgical Excision Procedure (LEEP) is used to treat pre-invasive HPV-mediated disease and patients are typically followed for 12 months after disease excision. This study aims to quantify the prevalence of high-grade disease at the time of the second follow-up colposcopy visit, in a practice setting that utilizes laser ablation in addition to LEEP. In a retrospective cohort study, consecutive patient charts were accessed through the electronic medical record system, ARIA, at the Tom Baker Cancer Centre, in Calgary, Alberta, from January 2010 to December 2015. Data was extracted and a REDCap database was used to compile pertinent information from charts meeting inclusion criteria. Descriptive and analytic statistics were performed. Of the 303 patients identified, 221 patients met inclusion criteria. 86% of these patients met discharge criteria from colposcopy after the second follow up visit. 31 (14%) were seen in a subsequent visit for abnormal findings. Of these, 7 (3.2%) underwent further treatment for high-grade disease/Cervical Intraepithelial Neoplasia (CIN 2/3). Of the 31, 23 (10.6%) had a third - negative - visit, resulting in discharge from colposcopy. One patient had a repeat LEEP for persistent Low-Grade Squamous Intraepithelial Lesion (LSIL). In summary, our data demonstrates a prevalence of 3.2% of high-grade disease at the time of a second colposcopic follow up visit after treatment, in a setting which frequently utilizes laser ablation in combination with LEEP, for large lesions. This recurrence rate is consistent with most published literature on recurrence rates of CIN2/3.


From dichotic listening to the irrelevant sound effect: a behavioural and neuroimaging analysis of the processing of unattended speech.
The assumption that ignoring irrelevant sound in a serial recall situation is identical to ignoring a non-target channel in dichotic listening is challenged. Dichotic listening is open to moderating effects of working memory capacity (Conway et al., 2001) whereas irrelevant sound effects (ISE) are not (Beaman, 2004). A right ear processing bias is apparent in dichotic listening, whereas the bias is to the left ear in the ISE (Hadlington et al., 2004). Positron emission tomography (PET) imaging data (Scott et al., 2004, submitted) show bilateral activation of the superior temporal gyrus (STG) in the presence of intelligible, but ignored, background speech and right hemisphere activation of the STG in the presence of unintelligible background speech. It is suggested that the right STG may be involved in the ISE and a particularly strong left ear effect might occur because of the contralateral connections in audition. It is further suggested that left STG activity is associated with dichotic listening effects and may be influenced by working memory span capacity. The relationship of this functional and neuroanatomical model to known neural correlates of working memory is considered.


EPA guidance on the early intervention in clinical high risk states of psychoses.
This guidance paper from the European Psychiatric Association (EPA) aims to provide evidence-based recommendations on early intervention in clinical high risk (CHR) states of psychosis, assessed according to the EPA guidance on early detection. The recommendations were derived from a meta-analysis of current empirical evidence on the efficacy of psychological and pharmacological interventions in CHR samples. Eligible studies had to investigate conversion rate and/or functioning as a treatment outcome in CHR patients defined by the ultra-high risk and/or basic symptom criteria. Besides analyses on treatment effects on conversion rate and functional outcome, age and type of intervention were examined as potential moderators. Based on data from 15 studies (n=1394), early intervention generally produced significantly reduced conversion rates at 6- to 48-month follow-up compared to control conditions. However, early intervention failed to achieve significantly greater functional improvements because both early intervention and control conditions produced similar positive effects. With regard to the type of intervention, both psychological and pharmacological interventions produced significant effects on conversion rates, but not on functional outcome relative to the control conditions. Early intervention in youth samples was generally less effective than in predominantly adult samples. Seven evidence-based recommendations for early intervention in CHR samples could have been formulated, although more studies are needed to investigate the specificity of treatment effects and potential age effects in order to tailor interventions to the individual treatment needs and risk status.


Neurological visual fields.
Neurological visual field defects represent lesions to the visual pathway, some of which may be life-threatening. It is, therefore, crucial that optometrists understand how to diagnose these lesions, so they may know when, and to whom to refer the patient. The following cases illustrate the management of patients with lesions to the prechiasmal, chiasmal, and postchiasmal visual pathway.


ChemNetworks: a complex network analysis tool for chemical systems.
Many intermolecular chemical interactions persist across length and timescales and can be considered to form a "network" or "graph." Obvious examples include the hydrogen bond networks formed by polar solvents such as water or alcohols. In fact, there are many similarities between intermolecular chemical networks like those formed by hydrogen bonding and the complex and distributed networks found in computer science. Contemporary network analyses are able to dissect the complex local and global changes that occur within the network over multiple time and length scales. This work discusses the ChemNetworks software, whose purpose is to process Cartesian coordinates of chemical systems into a network/graph formalism and apply topological network analyses that include network neighborhood, the determination of geodesic paths, the degree census, direct structural searches, and the distribution of defect states of network. These properties can help to understand the network patterns and organization that may influence physical properties and chemical reactivity. The focus of ChemNetworks is to quantitatively describe intermolecular chemical networks of entire systems at both the local and global levels and as a function of time. The code is highly general, capable of converting a wide variety of systems into a chemical network formalism, including complex solutions, liquid interfaces, or even self-assemblies.


Making free public healthcare attractive: optimizing health equity funds in Cambodia.
Following the introduction of user fees in Cambodia, Health Equity Funds (HEF) were developed to enable poor people access to public health services by paying public health providers on their behalf, including non-medical costs for hospitalised beneficiaries (HEFB). The national scheme covers 3.1 million pre-identified HEFB. Uptake of benefits, however, has been mixed and a substantial proportion of poor people still initiate care at private facilities where they incur considerable out-of-pocket costs. We examine the benefits of additional interventions compared to existing stand-alone HEF scenarios in stimulating care seeking at public health facilities among eligible poor people. We report on three configurations of HEF and their ability to attract HEFB to initiate care at public health facilities and their degree of financial risk protection: HEF covering only hospital services (HoHEF), HEF covering health centre and hospital services (CHEF), and Integrated Social Health Protection Scheme (iSHPS) that allowed non-HEFB community members to enrol in HEF. The iSHPS also used vouchers for selected health services, pay-for-performance for quantity and quality of care, and interventions aimed at increasing health providers' degree of accountability. A cross sectional survey collected information from 1636 matched HEFB households in two health districts with iSHPS and two other health districts without iSHPS. Respondents were stratified according to the three HEF configurations for the descriptive analysis. The findings indicated that the proportion of HEFB who sought care first from public health providers in iSHPS areas was 55.7%, significantly higher than the 39.5% in the areas having HEF with health centres (CHEF) and 13.4% in the areas having HEF with hospital services only (HoHEF). The overall costs (out-of-pocket and transport) associated with the illness episode were lowest for cases residing within iSHPS sites, US$10.4, and highest in areas where health centres were not included in the package (HoHEF), US$20.7. Such costs were US$19.5 at HEF with health centres (CHEF). The findings suggest that HEF encompassing health centre and hospital services and complemented by additional interventions are better than stand-alone HEF in attracting sick HEFB to public health facilities and lowering out-of-pocket expenses associated with healthcare seeking.


Polycyclic aromatic hydrocarbon exposure, obesity and childhood asthma in an urban cohort.
Exposure to traffic-related air pollutants, including polycyclic aromatic hydrocarbons (PAHs) from traffic emissions and other combustion sources, and childhood obesity, have been implicated as risk factors for developing asthma. However, the interaction between these two on asthma among young urban children has not been studied previously. Exposure to early childhood PAHs was measured by two week residential indoor monitoring at age 5-6 years in the Columbia Center for Children's Environmental Health birth cohort (n=311). Semivolatile [e.g., methylphenanthrenes] and nonvolatile [e.g., benzo(a)pyrene] PAHs were monitored. Obesity at age 5 was defined as a body mass index (BMI) greater than or equal to the 95th percentile of the year 2000 age- and sex-specific growth charts (Center for Disease Control). Current asthma and recent wheeze at ages 5 and 7 were determined by validated questionnaires. Data were analyzed using a modified Poisson regression in generalized estimating equations (GEE) to estimate relative risks (RR), after adjusting for potential covariates. Neither PAH concentrations or obesity had a main effect on asthma or recent wheeze. In models stratified by presence/absence of obesity, a significant positive association was observed between an interquartile range (IQR) increase in natural log-transformed 1-methylphenanthrene (RR [95% CI]: 2.62 [1.17-5.88] with IQRln=0.76), and 9-methylphenanthrene (2.92 [1.09-7.82] with IQRln=0.73) concentrations and asthma in obese children (n=63). No association in non-obese (n=248) children was observed at age 5 (Pinteraction<0.03). Similar associations were observed for 3-methylphenanthrene, 9-methylphenanthrene, and 3,6-dimethylphenanthrene at age 7. Obese young children may be more likely to develop asthma in association with greater exposure to PAHs, and methylphenanthrenes in particular, than non-obese children.


Exploring Cytokine Networks in Resistant Hypertension.
Controlling high blood pressure (BP) continues to be a major concern because the associated complications can lead to an increased risk of heart, brain, and kidney disease. Those with hypertension, despite lifestyle and diet modifications and pharmacotherapy, defined as resistant hypertension, are at increased risk for further risk for morbidity and mortality. Understanding inflammation in this population may provide novel avenues for treatment. This study aimed to examine a broad range of cytokines in adults with cardiovascular disease and identify specific cytokines associated with resistant hypertension. A secondary data analysis was conducted. The parent study included 156 adults with a history of myocardial infarction within the past 3-7 years and with a multiplex plasma analysis yielding a cytokine panel. A network analysis with lasso penalization for sparsity was performed to explore associations between cytokines and BP. Associated network centrality measures by cytokine were produced, and a community graph was extracted. A sensitivity analysis BP was also performed. Cytokines with larger node strength measures were sTNFR2 and CX3. The graphical network highlighted six cytokines strongly associated with resistant hypertension. Cytokines IL-29 and CCL3 were found to be negatively associated with resistant hypertension, whereas CXCL12, MMP3, sCD163, and sIL6Rb were positively associated with resistant hypertension. Understanding the network of associations through exploring oxidative stress and vascular inflammation may provide insight into treatment approaches for resistant hypertension.


Bacteriophages in Food Applications: From Foe to Friend.
Bacteriophages (phages) have traditionally been considered troublesome in food fermentations, as they are an important cause of starter-culture failure and trigger significant financial losses. In addition, from an evolutionary perspective, phages have contributed to the pathogenicity of many bacteria through transduction of virulence genes. In contrast, phages have played an important positive role in molecular biology. Moreover, these agents are increasingly being recognized as a potential solution to the detection and biocontrol of various undesirable bacteria, which cause either spoilage of food materials, decreased microbiological safety of foods, or infectious diseases in food animals and crops. The documented successful applications of phages and various phage-derived molecules are discussed in this review, as are many promising new uses that are currently under development.


Drug plasma monitoring in CML and GIST: A case-based discussion.
Drug plasma monitoring has emerged as an important tool to obtain optimal levels of a particular drug among individual patients. Plasma monitoring of imatinib levels would appear to be practical in cases where there is lack of response, heightened toxicity, or evidence of poor adherence to therapy. However, the potential role of monitoring plasma drug concentrations in guiding treatment decisions and optimizing patient therapy has yet to be established. Currently, there are no clinical recommendations regarding how to incorporate imatinib drug plasma monitoring in patients with either chronic myeloid leukemia or gastrointestinal stromal tumors, indications for which imatinib is approved. Here, the latest research and evidence regarding imatinib drug plasma monitoring is discussed. Three cases are presented to illustrate the most common examples where monitoring imatinib plasma concentrations may help to guide treatment decisions. These cases include a suboptimal response to imatinib treatment, lack of patient adherence to imatinib, and imatinib-related toxicity. By understanding the potential role of monitoring plasma imatinib concentrations in patients with chronic myeloid leukemia or gastrointestinal stromal tumors, physicians can identify patients who may benefit from drug plasma monitoring and consider incorporating the data in order to improve patient outcomes.


Machine learning for the prediction of sepsis-related death: a systematic review and meta-analysis.
Sepsis is accompanied by a considerably high risk of mortality in the short term, despite the availability of recommended mortality risk assessment tools. However, these risk assessment tools seem to have limited predictive value. With the gradual integration of machine learning into clinical practice, some researchers have attempted to employ machine learning for early mortality risk prediction in sepsis patients. Nevertheless, there is a lack of comprehensive understanding regarding the construction of predictive variables using machine learning and the value of various machine learning methods. Thus, we carried out this systematic review and meta-analysis to explore the predictive value of machine learning for sepsis-related death at different time points. PubMed, Embase, Cochrane, and Web of Science databases were searched until August 9th, 2022. The risk of bias in predictive models was assessed using the Prediction model Risk of Bias Assessment Tool (PROBAST). We also performed subgroup analysis according to time of death and type of model and summarized current predictive variables used to construct models for sepsis death prediction. Fifty original studies were included, covering 104 models. The combined Concordance index (C-index), sensitivity, and specificity of machine learning models were 0.799, 0.81, and 0.80 in the training set, and 0.774, 0.71, and 0.68 in the validation set, respectively. Machine learning outperformed conventional clinical scoring tools and showed excellent C-index, sensitivity, and specificity in different subgroups. Random Forest (RF) and eXtreme Gradient Boosting (XGBoost) are the preferred machine learning models because they showed more favorable accuracy with similar modeling variables. This study found that lactate was the most frequent predictor but was seriously ignored by current clinical scoring tools. Machine learning methods demonstrate relatively favorable accuracy in predicting the mortality risk in sepsis patients. Given the limitations in accuracy and applicability of existing prediction scoring systems, there is an opportunity to explore updates based on existing machine learning approaches. Specifically, it is essential to develop or update more suitable mortality risk assessment tools based on the specific contexts of use, such as emergency departments, general wards, and intensive care units.


L-Citrulline, but not L-arginine, prevents diabetes mellitus-induced glomerular hyperfiltration and proteinuria in rat.
Diabetes mellitus–induced oxidative stress causes increased renal oxygen consumption and intrarenal tissue hypoxia. Nitric oxide is an important determinant of renal oxygen consumption and electrolyte transport efficiency. The present study investigates whether l-arginine or l-citrulline to promote nitric oxide production prevents the diabetes mellitus–induced kidney dysfunction. Glomerular filtration rate, renal blood flow, in vivo oxygen consumption, tissue oxygen tension, and proteinuria were investigated in control and streptozotocin-diabetic rats with and without chronic l-arginine or l-citrulline treatment for 3 weeks. Untreated and l-arginine–treated diabetic rats displayed increased glomerular filtration rate (2600±162 versus 1599±127 and 2290±171 versus 1739±138 μL/min per kidney), whereas l-citrulline prevented the increase (1227±126 versus 1375±88 μL/min per kidney). Filtration fraction was increased in untreated diabetic rats because of the increase in glomerular filtration rate but not in l-arginine– or l-citrulline–treated diabetic rats. Urinary protein excretion was increased in untreated and l-arginine–treated diabetic rats (142±25 versus 75±7 and 128±7 versus 89±7 μg/min per kidney) but not in diabetic rats administered l-citrulline (67±7 versus 61±5 μg/min per kidney). The diabetes mellitus–induced tissue hypoxia, because of elevated oxygen consumption, was unaltered by any of the treatments. l-citrulline administered to diabetic rats increases plasma l-arginine concentration, which prevents the diabetes mellitus–induced glomerular hyperfiltration, filtration fraction, and proteinuria, possibly by a vascular effect.


Regulation of epinasty induced by 2,4-dichlorophenoxyacetic acid in pea and Arabidopsis plants.
The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) causes uncontrolled cell division and malformed growth in plants, giving rise to leaf epinasty and stem curvature. In this study, mechanisms involved in the regulation of leaf epinasty induced by 2,4-D were studied using different chemicals involved in reactive oxygen species (ROS) accumulation (diphenyleniodonium, butylated hydroxyanisole, EDTA, allopurinol), calcium channels (LaCl3), protein phosphorylation (cantharidin, wortmannin) and ethylene emission/perception (aminoethoxyvinyl glycine, AgNO3). The effect of these compounds on the epinasty induced by 2,4-D was analysed in shoots and leaf strips from pea plants. For further insight into the effect of 2,4-D, studies were also made in Arabidopsis mutants deficient in ROS production (rbohD, rbohF, xdh), ethylene (ein 3-1, ctr 1-1, etr 1-1), abscisic acid (aba 3.1), and jasmonic acid (coi 1.1, jar 1.1, opr 3) pathways. The results suggest that ROS production, mainly ·OH, is essential in the development of epinasty triggered by 2,4-D. Epinasty was also found to be regulated by Ca2+, protein phosphorylation and ethylene, although all these factors act downstream of ROS production. The use of Arabidopsis mutants appears to indicate that abscisic and jasmonic acid are not involved in regulating epinasty, although they could be involved in other symptoms induced by 2,4-D.


An energy-rich diet enhances expression of Na(+)/H(+) exchanger isoform 1 and 3 messenger RNA in rumen epithelium of goat.
Rumen epithelial Na(+)/H(+) exchanger (NHE) catalyzes the exchange of extracellular Na(+) for intracellular H(+). Thus, it is of importance in the maintenance of Na and pH homeostasis of rumen epithelial cells. We have tested the hypothesis that an increase in energy and protein intake induces alterations of NHE isoform 1, 2, and 3 (NHE1, NHE1, and NHE3, respectively) mRNA abundance in the rumen epithelium of goats. Goats (n = 26) were randomly allocated to 2 experiments (n = 16 in Exp. 1, and n = 10 in Exp. 2) and fed either peanut straw ad libitum [PNS, n = 8 in Exp. 1, and n = 5 in Exp. 2; 600 kJ of ME/(kg(0.75)·d)] or PNS + concentrate [CF, n = 8 in Exp. 1, and n = 5 in Exp. 2; 1,000 kJ of ME/(kg(0.75)·d)] for 42 d. Concentrate (400 g/d) was given daily (0800 to 1700 h) in 4 equal portions at 3-h intervals. In Exp. 1, the goats were euthanized 2 h after the last portion of concentrate was fed, and in Exp. 2, the goats were euthanized after a fasting period of 16 h. In Exp. 1, goats in the CF treatment exhibited a greater ruminal short-chain fatty acid (SCFA) concentration (140.6 ± 1.30 mM) compared with those in the PNS treatment (114.3 ± 3.11 mM; P < 0.001), and pH decreased from 6.9 ± 0.09 to 5.9 ± 0.04 (P < 0.001). Correspondingly, the mRNA expression of NHE1 and NHE3 in the rumen epithelium was greater by 20% (P = 0.041) and 25% (P = 0.043) for goats in the CF treatment than for those in the PNS treatment. However, in Exp. 2, 16 h of fasting abolished differences in ruminal SCFA concentration, pH, and NHE mRNA expression between goats in the CF and PNS treatments. In both Exp. 1 and 2, a positive correlation was observed between ruminal SCFA concentration and expression of mRNA in NHE1 and NHE3, whereas expression was negatively correlated with ruminal pH. In in vitro studies with isolated rumen epithelial cells from goats fed dried grass, exposure to pH of 6.8 or to 20 mM SCFA increased (P < 0.01) NHE1 and NHE3 mRNA expression, as compared with exposure to pH of 7.4 or the absence of SCFA. A combination of reduced pH (6.8) and SCFA (20 mM) further enhanced (P < 0.05) NHE1 and NHE3 mRNA expression, indicating synergism between an increased concentration of SCFA and low pH (P < 0.05). Messenger RNA expression of NHE2 did not vary in vitro with pH (6.8) or SCFA (20 mM) or in vivo in Exp. 1 and 2. Thus, diet-dependent rumen epithelial NHE1 and NHE3 expression is probably related to ruminal SCFA concentration and pH, but that is not the case with NHE2.


Recommendations on scuba diving in Birt-Hogg-Dubé syndrome.
Although very uncommon, severe injury and death can occur during scuba diving. One of the main causes of scuba diving fatalities is pulmonary barotrauma due to significant changes in ambient pressure. Pathology of the lung parenchyma, such as cystic lesions, might increase the risk of pulmonary barotrauma. Birt-Hogg-Dubé syndrome (BHD), caused by pathogenic variants in the FLCN gene, is characterized by skin fibrofolliculomas, an increased risk of renal cell carcinoma, multiple lung cysts and spontaneous pneumothorax. Given the pulmonary involvement, in some countries patients with BHD are generally recommended to avoid scuba diving, although evidence-based guidelines are lacking. We aim to provide recommendations on scuba diving for patients with BHD, based on a survey of literature on pulmonary cysts and pulmonary barotrauma in scuba diving. In our opinion, although the absolute risks are likely to be low, caution is warranted. Given the relative paucity of literature and the potential fatal outcome, patients with BHD with a strong desire for scuba diving should be informed of the potential risks in a personal assessment. If available a diving physician should be consulted, and a low radiation dose chest computed tomography (CT)-scan to assess pulmonary lesions could be considered.


Direct test of laser tunneling with electron momentum imaging.
Tunneling is often used to describe multiphoton ionization of rare gas atoms in infrared fields. We test the tunneling approximation and its nonadiabatic extension by measuring the unperturbed momentum distribution along the κ direction of a circularly polarized light pulse. We find substantial, but not total, agreement between our results and the predictions of the model. As predicted, the κ direction momentum distribution is Gaussian and its width increases with the square root of electric field strength. However, the width is 15% too large and we find no evidence of nonadiabatic effects as we approach the expected limits of the approximation.


Therapeutic alliance-not therapist competence or group cohesion-contributes to reduction of psychological distress in group-based mindfulness-based cognitive therapy for cancer patients.
Mindfulness-based cognitive therapy (MBCT) is an innovative evidence-based intervention in mental and somatic health care. Gaining knowledge of therapeutic factors associated with treatment outcome can improve MBCT. This study focused on predictors of treatment outcome of MBCT for cancer patients and examined whether group cohesion, therapeutic alliance, and therapist competence predicted reduction of psychological distress after MBCT for cancer patients. Moreover, it was examined whether therapist competence facilitated therapeutic alliance or group cohesion. Multilevel analyses were conducted on a subsample of patients collected in a larger randomized controlled trial on individual internet-based versus group-based MBCT versus treatment as usual in distressed cancer patients. The current analyses included the 84 patients who completed group-based MBCT out of 120 patients who were randomized to group-based MBCT. Group cohesion and therapist competence did not predict reduction in psychological distress, whereas therapeutic alliance did. In addition, therapist competence did not predict therapeutic alliance but was associated with reduced group cohesion. Our findings revealed that therapeutic alliance significantly contributed to reduction of psychological distress in MBCT for cancer patients. Elaborating the clinical implications of the predictive significance of therapeutic alliance might be of added value to enhance the potential effect of MBCT.


Tropical tropospheric ozone and biomass burning.
New methods for retrieving tropospheric ozone column depth and absorbing aerosol (smoke and dust) from the Earth Probe-Total Ozone Mapping Spectrometer (EP/TOMS) are used to follow pollution and to determine interannual variability and trends. During intense fires over Indonesia (August to November 1997), ozone plumes, decoupled from the smoke below, extended as far as India. This ozone overlay a regional ozone increase triggered by atmospheric responses to the El Niño and Indian Ocean Dipole. Tropospheric ozone and smoke aerosol measurements from the Nimbus 7 TOMS instrument show El Niño signals but no tropospheric ozone trend in the 1980s. Offsets between smoke and ozone seasonal maxima point to multiple factors determining tropical tropospheric ozone variability.


Propagation of ultrashort laser pulses through water.
In this paper, propagation of ultrashort pulses through a long 3.5 meter water channel was studied. Of particular interest was the attenuation of the beam at various lengths along the variable path length and to find an explanation of why the attenuation deviates from typical Beer Lambert law around 3 meters for ultrashort laser pulse transmission. Laser pulses of 10 fs at 75 MHz, 100 fs at 80 MHz and 300 fs at 1 KHz were employed to investigate the effects of pulse duration, spectrum and repetition rate on the attenuation after propagating through water up to 3 meters. Stretched pulse attenuation measurements produced from 10 fs at a frequency of 75 MHz were compared with the 10 fs attenuation measurements. Results indicate that the broad spectrum of the ultrashort pulse is the dominant reason for the observed decrease in attenuation after 3 meters of travel in a long water channel. The repetition rate is found not to play a significant role at least for the long pulse scenario in this reported attenuation studies.


Major adverse cardiovascular events associated with testosterone treatment: a pharmacovigilance study of the FAERS database.
Background and purpose: Testosterone is an essential sex hormone in maintaining masculine characteristics, which is prescribed for male hypogonadism as testosterone replacement treatment (TRT). Herein, we investigated long-standing controversies about the association between TRT and major adverse cardiovascular events (MACEs), based on real world adverse event (AE) reports, registered in the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: Publicly available FAERS data from 1 January 2004 to 31 December 2022 were retrieved from the Food and Drug Administration (FDA) website. The data mining protocol including the reporting odds ratio (ROR) and the Bayesian confidence propagation neural network (BCPNN) was applied to analyze overreporting caused by risk factors and MACEs, including TRT, morbidities, and ages. The ROR and the BCPNN were also applied to investigate the annually developing trend of pharmacovigilance (PV) signals in the real world, retrospectively. Results: A total of 3,057 cases referring to MACEs, with a median age of 57 years old (yo), were identified from 28,921 cases of testosterone users. MACEs related to PV signals have emerged since 2014, including cardiac death, non-fatal myocardial infarction, and non-fatal stroke. Myocardial infarction (MI) (ROR: 9.46; IC025: 3.08), acute myocardial infarction (AMI) (ROR: 16.20; IC025: 3.72), ischemic cardiomyopathy (ROR: 11.63; IC025: 2.20), and cardiomyopathy (ROR: 5.98; IC025: 1.96) were the most significant signals generated, and weaker signals included cardiac failure acute (ROR: 4.01; IC025: 0.71), cardiac arrest (ROR: 1.88; IC025: 0.56), and ventricular fibrillation (VF) (ROR: 2.38; IC025: 0.38). The time-to-onset (TTO) of MACEs was calculated with a median of 246 days for AMI. Conclusion: For myocardial infarction and cardiomyopathy, TRT statistically tended to increase the risk of MACEs, while for cardiac arrhythmia, cardiac failure, and stroke, TRT demonstrated beneficial effects among the population with morbidities, such as testosterone deficiency (TD), diabetes mellitus (DM), and hypertension. MACEs were rare but led to serious outcomes including significant increase in death and disability. Since 2018, and before 2014, reports referring to TRT associated with MACEs were relatively scarce, which indicated that there might be a considerable number of cases that went unrecorded, due to neglection. Health workers and testosterone users might pay more attention to testosterone-induced MACEs.


Triple Burden of Malnutrition among Children in India: Current Scenario and the Way Forward.
The triple burden of malnutrition (undernutrition, overnutrition and micronutrient deficiency) or TBM among under-five (U5) children is an increasingly recognised public health challenge. A literature search was conducted to identify studies published from 1976 to 2022, which had focused on information regarding different factors of child malnutrition. The findings were analysed and contextualised from policy and programmatic perspective. There is a high burden of various forms of malnutrition in India. Insufficient dietary intake and illnesses are immediate and most common causes of triple burden of malnutrition (TBM): (undernutrition, overnutrition and micronutrient deficiency). The other key factors associated with the TBM are lifestyle, nutritional practices, unsafe water, food insecurity, lack of sanitation & basic hygiene, unhealthy feeding & caring practices, inadequate health infrastructure, and suboptimal implementation of government nutrition schemes etc. There is scientific evidence that TBM has long term consequences on physical and mental development of children and has high cost to any society. The situation of TBM persists inspite of multiple ongoing government programs to tackle these challenges. The health service provision needs to move from the first 1,000 d to the first 3,000 d as well as focus on the interventions aimed at early childhood development. Multi-sectoral interventions through Anganwadi centres and schools (through education department) need to be conducted. The public health programs and primary healthcare services need to be realigned and health interventions should be implemented along with tackling social determinants of health and sustained community engagement and participation. Tackling TBM should be made a political priority. The life cycle approach for healthier children and society needs to be fully implemented.


Hybrid models identified a 12-gene signature for lung cancer prognosis and chemoresponse prediction.
Lung cancer remains the leading cause of cancer-related deaths worldwide. The recurrence rate ranges from 35-50% among early stage non-small cell lung cancer patients. To date, there is no fully-validated and clinically applied prognostic gene signature for personalized treatment. From genome-wide mRNA expression profiles generated on 256 lung adenocarcinoma patients, a 12-gene signature was identified using combinatorial gene selection methods, and a risk score algorithm was developed with Naïve Bayes. The 12-gene model generates significant patient stratification in the training cohort HLM & UM (n = 256; log-rank P = 6.96e-7) and two independent validation sets, MSK (n = 104; log-rank P = 9.88e-4) and DFCI (n = 82; log-rank P = 2.57e-4), using Kaplan-Meier analyses. This gene signature also stratifies stage I and IB lung adenocarcinoma patients into two distinct survival groups (log-rank P<0.04). The 12-gene risk score is more significant (hazard ratio = 4.19, 95% CI: [2.08, 8.46]) than other commonly used clinical factors except tumor stage (III vs. I) in multivariate Cox analyses. The 12-gene model is more accurate than previously published lung cancer gene signatures on the same datasets. Furthermore, this signature accurately predicts chemoresistance/chemosensitivity to Cisplatin, Carboplatin, Paclitaxel, Etoposide, Erlotinib, and Gefitinib in NCI-60 cancer cell lines (P<0.017). The identified 12 genes exhibit curated interactions with major lung cancer signaling hallmarks in functional pathway analysis. The expression patterns of the signature genes have been confirmed in RT-PCR analyses of independent tumor samples. The results demonstrate the clinical utility of the identified gene signature in prognostic categorization. With this 12-gene risk score algorithm, early stage patients at high risk for tumor recurrence could be identified for adjuvant chemotherapy; whereas stage I and II patients at low risk could be spared the toxic side effects of chemotherapeutic drugs.


E-cigarette puffing topography: The importance of assessing user behaviour to inform emissions testing.
Analysis of the chemical composition of e-cigarette emissions is an important step in determining whether e-cigarettes offer both individual and population-level harm reduction potential. Commonly, e-cigarette emissions for chemical analysis are collected when using e-cigarettes according to standardised puffing regimens, such as those recommended by the International Organization for Standardization (ISO) or the Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA). While the use of such standard puffing regimens affords a degree of uniformity between studies and are also recommended by regulatory authorities who require the submission of e-cigarette emissions data to make decisions regarding allowing a product to be commercially marketed, the standardised regimens do not necessarily reflect human puffing behaviour. This can lead to under- or over-estimating real-world emissions from e-cigarettes and inaccuracy in determining their harm reduction potential. In this review, we describe how human puffing behaviour (topography) information can be collected both in the clinical laboratory and in the real world using a variety of different methodologies. We further discuss how this information can be used to dictate e-cigarette puffing regimens for collecting emissions for chemical analyses and how this may lead to better predictions both of human yields of e-cigarette emissions constituents and of risk assessments to predict e-cigarette tobacco harm reduction potential.


Vecuronium infusion requirements in children during halothane-narcotic-nitrous oxide, isoflurane-narcotic-nitrous oxide, and narcotic-nitrous oxide anesthesia.
We were interested in determining the infusion rate of vecuronium required to maintain approximately 95% neuromuscular blockade in children during halothane-narcotic-nitrous oxide (0.8% end-tidal concentration), isoflurane-narcotic-nitrous oxide (1.0% end-tidal concentration), or narcotic-nitrous oxide anesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity (Datex NMT) of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10-s intervals. Effective vecuronium infusion requirements averaged 1.5 +/- 0.1 micrograms.kg-1.min-1 (mean +/- SEM) during isoflurane-narcotic-nitrous oxide anesthesia, 1.9 +/- 0.1 micrograms.kg-1.min-1 during halothane-narcotic-nitrous oxide anesthesia, and 2.4 +/- 0.3 micrograms.kg-1.min-1 during narcotic-nitrous oxide anesthesia. Infusion requirements significantly decreased after the first 30 min of infusion in the presence of both potent inhalation anesthetics, but did not change with time during narcotic-nitrous oxide anesthesia. There was no evidence of decreasing infusion requirements during prolonged vecuronium infusion (2.5 h). There was no difference in the rate of spontaneous or pharmacologically induced recovery between anesthetic groups. The mean recovery index (T25-75) after termination of the infusion was 13.7 min.


Early-phase thin-slice CT in the diagnosis of small insulinomas.
Insulinomas, which are generally smaller than 2 cm, may be difficult to detect by routine imaging modalities including abdominal ultrasonography, computed tomography, and magnetic resonance imaging. Although preoperative detection of insulinomas is essential for operative planning, it is often challenging due to their small size. While arterial stimulation and venous sampling has been used in patients with insulinomas it has been largely supplanted by early-phase thin-slice computed tomography. We report three patients with insulinomas, which were not detected by routine computed tomography scan, but were successfully imaged using early-phase thin-slice computed tomography. Enucleation was performed in all patients based on preoperative imaging. All three patients had an unremarkable postoperative course. Early-phase thin-slice computed tomography is recommended for the preoperative identification of insulinomas. This non-invasive imaging technique should be considered before performing arterial stimulation and venous sampling.


Molecular hydrogen: potential in mitigating oxidative-stress-induced radiation injury 1.
Uncontrolled production of oxygen and nitrogen radicals results in oxidative and nitrosative stresses that impair cellular functions and have been regarded as causative common denominators of many pathological processes. In this review, we report on the beneficial effects of molecular hydrogen in scavenging radicals in an artificial system of •OH formation. As a proof of principle, we also demonstrate that in rat hearts in vivo, administration of molecular hydrogen led to a significant increase in superoxide dismutase as well as pAKT, a cell survival signaling molecule. Irradiation of the rats caused a significant increase in lipid peroxidation, which was mitigated by pre-treatment of the animals with molecular hydrogen. The nuclear factor erythroid 2-related factor 2 is regarded as an important regulator of oxyradical homeostasis, as well as it supports the functional integrity of cells, particularly under conditions of oxidative stress. We suggest that the beneficial effects of molecular hydrogen may be through the activation of nuclear factor erythroid 2-related factor 2 pathway that promotes innate antioxidants and reduction of apoptosis, as well as inflammation.


Availability of Research Data in High-Impact Addiction Journals with Data Sharing Policies.
Although data sharing is one of the primary measures proposed to improve the integrity and quality of published research, studies show it remains the exception not the rule. The current study examines the availability of data in papers reporting the results of analyses of empirical data from original research in high-impact addiction journals. Thirteen high-impact journals with data sharing policies were selected from those included in the substance abuse category of the 2018 Clarivate Analytics' Journal Citation Report. The first 10 full or short original research reports that included empirical data in the most recent complete issue of each journal were electronically searched and reviewed for reference to where their data can be obtained and for a formal data sharing statement. Only eight of the 130 papers contained a data sharing statement in their text or supplementary online materials, and just one contained a direct link to the data analyzed. Data sharing was rare in the 13 high-impact addiction journals reviewed. The nature of the data reported in addiction journals might partly explain this. Currently, data sharing is not a procedure likely to improve the quality and integrity of published addiction research.


A key genetic factor governing arabinan utilization in the gut microbiome alleviates constipation.
Impaired gastrointestinal motility is associated with gut dysbiosis. Probiotics, such as Bifidobacteria, can improve this bowel disorder; however, efficacy is strain-dependent. We determine that a genetic factor, the abfA cluster governing arabinan utilization, in Bifidobacterium longum impacts treatment efficacy against functional constipation (FC). In mice with FC, B. longum, but not an abfA mutant, improved gastrointestinal transit time, an affect that was dependent upon dietary arabinan. abfA genes were identified in other commensal bacteria, whose effects in ameliorating murine FC were similarly abfA-dependent. In a double-blind, randomized, placebo-controlled clinical trial, supplementation with abfA-cluster-carrying B. longum, but not an abfA-deficient strain, enriched arabinan-utilization residents, increased beneficial metabolites, and improved FC symptoms. Across human cohorts, abfA-cluster abundance can predict FC, and transplantation of abfA cluster-enriched human microbiota to FC-induced germ-free mice improved gut motility. Collectively, these findings demonstrate a role for microbial abfA cluster in ameliorating FC, establishing principles for genomics-directed probiotic therapies.


Targeting c-Myc as a novel approach for hepatocellular carcinoma.
Hepatocelluar carcinoma (HCC) is the most lethal cancer in the world. Most HCC over-express c-Myc, which plays a critical role in regulating cellular growth, differentiation and apoptosis in both normal and neoplastic cells. c-Myc is among the most frequently overexpressed genes in human cancers. Overexpression of c-Myc in hepatic cells leads to development of hepatocellular carcinoma. Here, we review the current progress in understanding physiologic function and regulation of c-Myc as well as its role in hepatic carcinogenesis and discuss the association of c-Myc activation in chronic hepatitis B infection and the upregulation of HIF-1/VEGF. We also explore the possibility of treating HCC by inhibiting c-Myc and examine the pros and cons of such an approach. Although this strategy is currently not available in clinics, with recent advances in better drug design, pharmacokinetics and pharmacogenetics, inhibition of c-Myc might become a novel therapy for HCC in the future.


Timing of nutritional interventions in very-low-birth-weight infants: optimal neurodevelopment compared with the onset of the metabolic syndrome.
Recent nutritional research in very-low-birth-weight (VLBW) infants is focused on the prevention of protein malnutrition during the first postnatal weeks. At this early age, nutritional protein fortification depends on amino acid infusion via a central vein because of the immature gastrointestinal tract. In 2010 new guidelines on nutrition were proposed by the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition nutrition committee. In particular, the relative increase in the protein fraction in the nutrition of these infants aims to prevent early postnatal weight loss, to prevent morbidity, and to stimulate neurodevelopment. On the other hand, an increasing number of follow-up studies in VLBW infants indicate that, in particular, those infants who show rapid growth after preterm birth are at risk of metabolic consequences and cardiovascular disease later in life. In this review, we describe the quest to develop a customized diet that offers optimal nutrition at several time points of growth and development during the first year of life. This diet should prevent early malnutrition, enhance neurodevelopment, and limit the increase in total body fat during the first 6 mo. We question whether one type of early diet suffices for normal neurodevelopment with a normal body composition in later life or whether we need several types of diet at various stages of development.


Mechanical, thermal, and interfacial properties of green composites with ramie fiber and soy resins.
Fully biodegradable, green composites were fabricated with ramie fibers and modified soy flour (MSF) resin. Defatted soy flour (SF) was modified by a lab-scale filtration system to improve its mechanical, interfacial, and thermal properties through increasing the protein content. The protein content of SF was increased from 53.1 to 67.5% by filtering out soluble sugars using a microfiber-based filter. Tensile stress and Young's modulus of MSF resins were 35.5 and 1411.7 MPa, respectively, which were significantly higher than those (12.7 and 379.3 MPa) of SF resins. Interfacial shear strength of single ramie fibers with MSF resins ranged from 8.8 to 15.2 MPa, which were about 40-50% higher than those obtained with SF resins. Tensile stress and Young's modulus of ramie fiber-reinforced composites were 88.0 MPa and 2.94 GPa with SF resin and 103.8 MPa and 3.15 GPa with MSF resin.


An extreme codon preference strategy: codon reassignment.
We argue that in animal mitochondria codon reassignments, such as those for AGA and AGG from arginine to serine or of AUA from isoleucine to methionine, are the result of an interplay between biased mutational forces and selective ones. In particular, there is a marked tendency for animal mitochondria to have very small genomes and to minimize their investment in components required for gene expression. These tendencies are expressed as a reduction in the diversity of tRNA isoacceptor species. In our view, the pressure to simplify tRNA populations, together with mutational bias against certain codons, will account for the codon reassignments observed in animal mitochondria. A parallel to the major codon bias in microorganisms, which likewise tends to reduce the diversity of the tRNA isoacceptor populations under fast growth conditions, may be drawn. Therefore, we suggest that codon reassignments are usefully viewed as an extreme form of codon bias.


[Reconstructive model of organs of the embryonal retroperitoneal space].
Data on formation of organocomplexes in retroperitoneal space (gonadomesonephric, adreno-renal and pancreatoduodenal) and dynamics of their topographo-anatomic interrelations during human intrauterine development are presented.


Antiplatelet drugs may increase the risk for checkpoint inhibitor-related pneumonitis in advanced cancer patients.
Immune checkpoint inhibitors (ICIs) are indicated for various cancers and are the mainstay of cancer immunotherapy. They are often associated with ICI-related pneumonitis (CIP), however, hindering a favorable clinical course. Recently, non-oncology concomitant drugs have been reported to affect the efficacy and toxicity of ICIs; however, the association between these drugs and the risk for CIP is uncertain. The aim of this study was to assess the impact of baseline concomitant drugs on CIP incidence in ICI-treated advanced cancer patients. This was a single-center retrospective study that included a cohort of 511 patients with advanced cancer (melanoma and non-small-cell lung, head and neck, genitourinary, and other types of cancer) treated with ICIs. Univariable analysis was conducted to identify baseline co-medications associated with CIP incidence. A propensity score matching analysis was used to adjust for potential CIP risk factors, and multivariable analysis was carried out to assess the impact of the identified co-medications on CIP risk. Forty-seven (9.2%) patients developed CIP. In these patients, the organizing pneumonia pattern was the dominant radiological phenotype, and 42.6% had grade ≥3 CIP, including one patient with grade 5. Of the investigated baseline co-medications, the proportion of antiplatelet drugs (n = 50, 9.8%) was higher in patients with CIP (23.4% versus 8.4%). After propensity score matching, the CIP incidence was higher in patients with baseline antiplatelet drugs (22% versus 6%). Finally, baseline antiplatelet drug use was demonstrated to increase the risk for CIP incidence regardless of cancer type (hazard ratio, 3.46; 95% confidence interval 1.21-9.86). An association between concomitant antiplatelet drug use at baseline and an increased risk for CIP was seen in our database. This implies the importance of assessing concomitant medications for CIP risk management.


Pubic osteolysis simulating a malignant lesion. A case report with long-term follow-up.
Pubic osteolysis is a rare pathology characterized by a painful radiographic destructive changes in the pubic rami, pubis or pubic symphysis that often follows a post-traumatic event. The etiology is unclear but it is a benign lesion, frequently misinterpreted as malignant. We report a case of a 54-year-old woman with pubic osteolysis mimicking a malignant lesion, diagnosed after open bone biopsy, conservatively treated without any sequelae and followed-up 10 years after the end of treatment. Although in the majority of the reported cases, a previous trauma has been commonly referred, in our case the patient did not refer to any cause before the onset of clinical symptoms. Knowledge of this entity is important to avoid invasive diagnostic procedures, costly investigations or overtreatment.


Magnetic Resonance Imaging of Non-Puerperal Complete Uterine Inversion.
Uterine inversion is shortly described as the indentation and depression of the fundic area extending downwards up to the different levels of the birth canal till vaginal opening. Clinical diagnosis of uterine inversion is difficult due to its non-specific symptoms and physical examination. Ultrasonography is the most practical modality for radiological evaluation, but it is inadequate to determine the exact nature of this condition and making the differential diagnosis. In this case, we present the main MRI findings of non-puerperal complete uterine inversion caused by a giant leiomyoma.


Efficacy of an insole shoe wedge and augmented pressure sensor for gait training in individuals with stroke: a randomized controlled trial.
To determine whether external feedback to promote symmetrical weight distribution during standing and walking would improve gait performance and balance in people with stroke. Randomized, controlled, assessor-blinded trial. Rehabilitation unit and physical therapy department. Thirty-five individuals with stroke (mean (SD) age = 53.0 (9.3) years) were randomly assigned to an experimental (n = 17) or control group (n = 18). Time post stroke was less than six months for most subjects (n = 27, 77%). Subjects participated in 15 rehabilitation sessions including 30 minutes of gait retraining per session. During gait retraining, the experimental group used an insole shoe wedge and sensors set-up (I-ShoWS) while the control group received a conventional programme. The I-ShoWS set-up consisted of a wedge insole and a footswitch for the non-paretic leg and a pressure sensor on the paretic leg. Gait speed, step length and single support time asymmetry ratio, balance and amount of load on paretic leg during stance were evaluated twice: one day before and after training. The experimental group demonstrated significant increase in standing and gait symmetry compared with the control group (P < 0.05). They demonstrated 3 times greater improvement in gait speed than the control group (P = 0.02). Balance improvement was significantly greater for the experimental than for the control group (P < 0.05). Gait retraining using the I-ShoWS set-up was more effective in restoration of gait speed, standing and walking symmetry and balance than a conventional treatment programme. These results indicate the benefit of implementing feedback during gait retraining.


Accuracy of the API Campy system, the Vitek 2 Neisseria-Haemophilus card and matrix-assisted laser desorption ionization time-of-flight mass spectrometry for the identification of Campylobacter and related organisms.
Biochemical identification of Campylobacter and related organisms is not always specific, and may lead to diagnostic errors. The API Campy, the Vitek 2 system and matrix-assisted desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) are commercially available methods that are routinely used for the identification of these microorganisms. In the present study, we used 224 clinical isolates and ten reference strains previously identified by multiple PCR assays, whole cell protein profiling and either DNA-DNA hybridization or sequencing analysis to compare the reliability of these three methods for the identification of Campylobacter and related pathogens. The API Campy accurately identified 94.4% of Campylobacter jejuni ssp. jejuni and 73.8% of Campylobacter coli, but failed to correctly identify 52.3% of other Epsilobacteria. The Vitek 2 Neisseria-Haemophilus card correctly identified most C. jejuni ssp.jejuni (89.6%) and C. coli (87.7%) strains, which account for the majority of campylobacterioses reported in humans, but it failed in the identification of all of the other species. Despite a good identification rate for both C. jejuni ssp. jejuni and C. coli, both methods showed poor sensitivity in the identification of related organisms, and additional tests were frequently needed. In contrast to API Campy and Vitek, MALDI-TOF MS correctly identified 100% of C. coli and C. jejuni strains tested. With an overall sensitivity of 98.3% and a short response time, this technology appears to be a reliable and promising method for the routine identification of Campylobacter and other Epsilobacteria.


Xe133 elimination from human fat during negative- and positive-pressure breathing.
The elimination of Xe133 from a deposit in the subcutaneous adipose tissue outside the anterior tibial muscle was recorded by an external scintillation detector in 16 human subjects during normal breathing, negative-pressure breathing (-20 cm H2o), and positive-pressure breathing (+20 cm H2O). The ambient temperature was kept at 28.0 degrees C +/- 0.1 degrees, which can be considered a neutral temperature. The xenon clearance rate was increased during negative-pressure breathing by a mean of 68% and decreased during positive-pressure breathing by a mean of 73% when compared to normal breathing. The xenon-elimination rates during the different conditions may reflect corresponding changes in adipose-tissue blood flow. Because both negative- and positive-pressure breathing may occur during diving, the uptake and elimination of inert gases in adipose tissue of a diver may be influenced; thus, the risk of decompression sickness might also be affected. The results may therefore be of importance in diving routines and in the construction of breathing apparatus for divers.


CD11b+ lung dendritic cells at different stages of maturation induce Th17 or Th2 differentiation.
Dendritic cells (DC) in the lung that induce Th17 differentiation remain incompletely understood, in part because conventional CD11b+ DCs (cDC2) are heterogeneous. Here, we report a population of cDCs that rapidly accumulates in lungs of mice following house dust extract inhalation. These cells are Ly-6C+, are developmentally and phenotypically similar to cDC2, and strongly promote Th17 differentiation ex vivo. Single cell RNA-sequencing (scRNA-Seq) of lung cDC2 indicates 5 distinct clusters. Pseudotime analysis of scRNA-Seq data and adoptive transfer experiments with purified cDC2 subpopulations suggest stepwise developmental progression of immature Ly-6C+Ly-6A/E+ cDC2 to mature Ly-6C-CD301b+ lung resident cDC2 lacking Ccr7 expression, which then further mature into CD200+ migratory cDC2 expressing Ccr7. Partially mature Ly-6C+Ly-6A/E-CD301b- cDC2, which express Il1b, promote Th17 differentiation. By contrast, CD200+ mature cDC2 strongly induce Th2, but not Th17, differentiation. Thus, Th17 and Th2 differentiation are promoted by lung cDC2 at distinct stages of maturation.


Microbiologic evaluation of cutaneous cellulitis in adults.
Fifty patients with cellulitis were evaluated prospectively using cultures of aspirates from the advancing edge of cellulitis, skin biopsy specimens, and blood. Potential microbial pathogens were isolated in 13 patients. Biopsy specimen cultures were positive in ten patients, while aspirate and blood cultures were positive in five and two, respectively. Aspirate, biopsy, or blood cultures were more often positive in patients with apparent primary lesions than in patients without such lesions. Apparent primary sites of infection were identified and cultured in 24 patients. beta-Hemolytic streptococci were isolated from 17 primary lesions, and coagulase-positive staphylococci were present in 13. Both organisms were isolated from ten primary lesions. Among patients with positive aspirate, biopsy, and/or blood cultures, the same pathogens were also isolated from primary sites in ten of ten patients. Clinical features, including temperature, white blood cell count, and erythrocyte sedimentation rate, were not predictive of positive aspirate, biopsy, or blood cultures. These cultures provided no microbiologic information that was not obtainable from culture of primary lesions.


A physics-based analytical model of absorbed dose from primary, leakage, and scattered photons from megavoltage radiotherapy with MLCs.
A burgeoning population of cancer survivors is at risk of late health effects following radiation therapy including second cancers, with the majority of these cancers occurring outside of the treatment volume of the primary cancer. Commercial radiotherapy treatment planning systems underestimate the out-of-field dose. Previous analytical models of out-of-field dose have assumed radial symmetry and/or approximated the dimensions of collimators as semi-infinite planes. The purpose of this work was to develop a physics-based analytical model of total absorbed dose from primary, scattered, and leakage radiation for square fields from a 6 MV beam at any arbitrary point in a phantom, including in-plane, cross-plane, and out-of-plane locations. The model includes the essential physics of radiation transport through beam-limiting-devices including rounded edges of MLC leaves. The model agreed well with measurements and Monte Carlo simulations of absorbed dose in a water-box phantom and was validated for field-sizes ranging from 2 [Formula: see text] 2 to 20 [Formula: see text] 20 cm2. The signed and unsigned average percent differences were [Formula: see text] and 15.9%, respectively, for all points and field-sizes considered. An extended gamma index analysis reveals a 92% pass rate with criteria of 3 mm distance-to-agreement, 3% relative dose difference in-field, and 3 mGy Gy-1 absolute dose difference out-of-field. The average wall-clock time to calculate dose to one million points was 3.3 min. These results suggest that it is feasible to calculate absorbed dose from both therapeutic and stray radiation using physics-based analytical models with good accuracy, thus overcoming a major obstacle to routinely assessing exposures. Additionally, this work demonstrates the importance of relaxing certain simplifications such as assuming a radially symmetric stray-dose distribution. Because the model is physics-based and may be reconfigured according to the dimensions of beam-limiting-devices, adapting it to other treatment units should be straight forward. Uses for such a model include clinical and research applications, such as clinical trials and epidemiological studies.


Challenges of self-management when living with multiple chronic conditions: systematic review of the qualitative literature.
To explore the perspectives of patients who live with multiple chronic conditions as they relate to the challenges of self-management. On September 30, 2013, we searched MEDLINE, EMBASE, and CINAHL using relevant key words including chronic disease, comorbidity, multimorbidity, multiple chronic conditions, self-care, self-management, perspective, and perception. Three reviewers assessed and extracted the data from the included studies after study quality was rated. Qualitative thematic synthesis method was then used to identify common themes. Twenty-three articles met the inclusion criteria, with most coming from the United States. Important themes raised by people living with multiple chronic conditions related to their ability to self-manage included living with undesirable physical and emotional symptoms, with pain and depression highlighted. Issues with conflicting knowledge, access to care, and communication with health care providers were raised. The use of cognitive strategies, including reframing, prioritizing, and changing beliefs, was reported to improve people's ability to self-manage their multiple chronic conditions. This study provides a unique view into patients' perspectives of living with multiple chronic conditions, which are clearly linked to common functional challenges as opposed to specific diseases. Future policy and programming in self-management support should be better aligned with patients' perspectives on living with multiple chronic conditions. This might be achieved by ensuring a more patient-centred approach is adopted by providers and health service organizations.


High avidity cytotoxic T lymphocytes can be selected into the memory pool but they are exquisitely sensitive to functional impairment.
High avidity cytotoxic T lymphocytes (CTL) are important in viral clearance and anti-tumor immunity, however, mechanisms for their optimal generation and maintenance in vivo remain unclear. Immunizing mice with an antibody-DNA vaccine encoding a single CTL epitope, induces a 100 fold higher avidity response than peptide vaccination with the identical epitope. The high avidity response is retained into memory and can be efficiently reactivated with an antibody-DNA boost. In contrast, reactivation of high avidity CTL with peptide, stimulated responses with a significant drop in avidity, suggesting loss or conversion of the high avidity CTL to lower avidity. Similarly, high avidity T cells maintained ex vivo were exquisitely sensitive to signaling with low doses of peptide (1 ng/ml) giving optimal TCR stimulation and resulting in retained avidity, proliferation and ability to kill specific targets. In contrast, high avidity T cells maintained ex vivo with supraoptimal TCR stimulation (10 µg/ml peptide) resulted in reduced avidity and failure to kill tumor cells. They also failed to proliferate, showed a significant increase in apoptosis and expressed high levels of the exhaustion marker programmed death-1 (PD-1) and low levels of the lymphocyte-activation gene 3 (LAG-3). This suggests high avidity T cells are recruited to the memory pool but can be lost by supraoptimal stimulation in vitro and in vivo. This is characterized by loss of function and an increase in cell death. The remaining CTL, exhibit low functional avidity that is reflected in reduced anti-tumor activity. This could contribute to failure of the immune system to control the growth of tumors and has implications for vaccination strategies and adoptive transfer of T cells.


Biomimetic synthesis of gold nanocrystals using a reducing amphiphile.
The first synthesis of a chelating and reactive surfactant derived from citric acid and a short silicone as hydrophobic tail is described. Aqueous solutions of this reactive amphiphile spontaneously induce gold ion reduction, particle nucleation, and further direct crystal growth. The process, both pH and light dependent, occurs through lipid-directed assembly of metal ions, their reduction and subsequent lipid-directed growth to yield ultrathin (approximately 7 nm thick) quasi two-dimensional gold nanocrystals.