Air pollution and daily hospital admissions in metropolitan Los Angeles.
We used daily time-series analysis to evaluate associations between ambient carbon monoxide, nitrogen dioxide, particulate matter [less than and equal to] 10 microm in aerodynamic diameter (PM(10)), or ozone concentrations, and hospital admissions for cardiopulmonary illnesses in metropolitan Los Angeles during 1992-1995. We performed Poisson regressions for the entire patient population and for subgroups defined by season, region, or personal characteristics, allowing for effects of temporal variation, weather, and autocorrelation. CO showed the most consistently significant (p<0.05) relationships to cardiovascular admissions. A wintertime 25th-75th percentile increase in CO (1.1-2.2 ppm) predicted an increase of 4% in cardiovascular admissions. NO(2), and, to a lesser extent, PM(10) tracked CO and showed similar associations with cardiovascular disease, but O(3) was negatively or nonsignificantly associated. No significant demographic differences were found, although increased cardiovascular effects were suggested in diabetics, in whites and blacks (relative to Hispanics and Asians), and in persons older than 65 years of age. Pulmonary disease admissions associated more with NO(2) and PM(10) than with CO. Pulmonary effects were generally smaller than cardiovascular effects and were more sensitive to the choice of model. We conclude that in Los Angeles, atmospheric stagnation with high primary (CO/NO(2)/PM(10)) pollution, most common in autumn/winter, increases the risk of hospitalization for cardiopulmonary illness. Summer photochemical pollution (high O(3)) apparently presents less risk.


Spectrotemporal receptive field properties of single units in the primary, dorsocaudal and ventrorostral auditory cortex of the guinea pig.
We report the spectrotemporal response properties of single units in the primary (A1) and dorsocaudal (DC) fields, and the ventrorostral belt of the urethane-anaesthetised guinea pig auditory cortex. Using reverse correlation analysis, spectrotemporal receptive fields (STRFs) were constructed and subsequently classified according to a novel qualitative scheme that was based on the duration and bandwidth of excitatory and inhibitory regions within the STRF. The STRFs of units in both A1 and DC showed either broad-band (> or = 1 octave) or narrow-band (< 1 octave) excitatory and inhibitory regions occurring either alone or together. The excitatory regions were of short duration (lasting for <50 ms) or more sustained (up to about 100 ms) and inhibitory areas either followed excitation or were located as inhibitory sidebands along the high- and low-frequency edges of the excitatory regions. Inhibitory areas that followed excitatory regions were found to be either short lasting (10-20 ms) or longer lasting (up to 200 ms or more). The STRFs recorded from each cortical area indicated temporal response properties consistent with those shown by traditional peristimulus time histogram analysis. Overall, fields A1 and DC showed no significant differences in the distribution of STRF types. Thus, it appears that both fields display similar spectrotemporal sensitivities to auditory stimuli and therefore, appear to process such stimuli in a parallel fashion. Single units recorded in the ventrorostral belt area showed STRF types similar to those recorded in A1 and DC. However, the proportions of STRF types were significantly different, suggesting a difference in spectrotemporal processing between the ventrorostral belt and the core areas.


Design and evaluation of statistical control procedures: applications of a computer "quality control simulator" program.
A computer simulation program has been developed to aid in designing and evaluating statistical control procedures. This "QC stimulator" (quality control) program permits the user to study the effects of different factors on the performance of quality-control procedures. These factors may be properties of the analytical procedure, characteristics of the instrument system, or conditions for the quality-control procedure. The performance of a control procedure is characterized by its probability for rejection, as estimated at several different magnitudes of random and systematic error. These performance characteristics are presented graphically by power functions-plots of the probability for rejection vs the size of the analytical errors. The utility of this stimulation tool is illustrated by application to multi-rule single-value procedures, mean and range procedures, and a trend analysis procedure. Careful choice of control rules is necessary to minimize false rejections and to optimize error detection with multi-rule procedures. Control limits must be carefully calculated for optimum performance of mean and range procedures. The level of significance for testing control must be carefully selected for the trend analysis procedure.


Detection of COVID-19 and its pulmonary stage using Bayesian hyperparameter optimization and deep feature selection methods.
Since the first case of COVID-19 was reported in December 2019, many studies have been carried out on artificial intelligence for the rapid diagnosis of the disease to support health services. Therefore, in this study, we present a powerful approach to detect COVID-19 and COVID-19 findings from computed tomography images using pre-trained models using two different datasets. COVID-19, influenza A (H1N1) pneumonia, bacterial pneumonia and healthy lung image classes were used in the first dataset. Consolidation, crazy-paving pattern, ground-glass opacity, ground-glass opacity and consolidation, ground-glass opacity and nodule classes were used in the second dataset. The study consists of four steps. In the first two steps, distinctive features were extracted from the final layers of the pre-trained ShuffleNet, GoogLeNet and MobileNetV2 models trained with the datasets. In the next steps, the most relevant features were selected from the models using the Sine-Cosine optimization algorithm. Then, the hyperparameters of the Support Vector Machines were optimized with the Bayesian optimization algorithm and used to reclassify the feature subset that achieved the highest accuracy in the third step. The overall accuracy obtained for the first and second datasets is 99.46% and 99.82%, respectively. Finally, the performance of the results visualized with Occlusion Sensitivity Maps was compared with Gradient-weighted class activation mapping. The approach proposed in this paper outperformed other methods in detecting COVID-19 from multiclass viral pneumonia. Moreover, detecting the stages of COVID-19 in the lungs was an innovative and successful approach.


Multidisciplinary approach including receptor radionuclide therapy with 90Y-DOTATOC ([90Y-DOTA0, Tyr3]-octreotide) and 177Lu-DOTATATE ([177Lu-DOTA0, Tyr3]-octreotate) in ectopic cushing syndrome from a metastatic gastrinoma: a promising proposal.
To present a case of a young woman with Cushing syndrome caused by ectopic production of adrenocorticotropic hormone from a metastatic pancreatic gastrin-secreting endocrine carcinoma, who had a good response to combination peptide receptor radionuclide therapy. We review the history, physical examination, laboratory investigations, and radiographic findings in this unusual patient. Moreover, the multimodal interventions are described and discussed. In a 38-year-old woman with typical signs of cortisol excess, laboratory studies revealed diabetes mellitus, hypokalemia, and high levels of adrenocorticotropic hormone, plasma cortisol, and urinary cortisol. Abdominal computed tomography showed a 4-cm pancreatic mass and multiple metastatic lesions in the liver, and ectopic Cushing syndrome was diagnosed. Treatment consisted of surgical debulking of the tumor, ketoconazole, somatostatin analogues, chemoembolization of the liver metastatic lesions, and peptide receptor radionuclide therapy with the radiolabeled somatostatin analogues 90Y-DOTATOC ([90Y-DOTA0, Tyr3]-octreotide) and 177Lu-DOTATATE ([177Lu-DOTA0, Tyr3]-octreotate). The 5 1/2-year follow-up showed positive results, which included complete regression of all clinical and hormonal evidence of the tumor and substantial decrease in the size and number of hepatic metastatic lesions. The patient achieved and still maintains an optimal quality of life. To the best of our knowledge, this is the first report of a multidisciplinary approach including peptide receptor radionuclide therapy with 90Y-DOTATOC and 177Lu-DOTATATE, which proved to be effective in improving clinical outcome in a case of metastatic endocrine carcinoma of the pancreas in conjunction with ectopic Cushing syndrome. In this unusual case, the patient has one of the longest durations of survival in this setting described in the literature.


Pharyngeal flap outcomes for velopharyngeal insufficiency: Evaluation of speech, obstructive sleep apnea, and velopharyngeal anatomy.
The purpose of this study was to evaluate the speech outcomes, reveal postoperative rates of obstructive sleep apnea, and characterize changes in the pharyngeal flap and velopharyngeal anatomy following pharyngeal flap surgery for velopharyngeal insufficiency. A retrospective chart was reviewed for patients with clefts who underwent pharyngeal flap surgery between November 2020 and November 2021. The data collected included age, gender, cleft palate type, age at pharyngeal flap surgery, postoperative complications, age and type of primary palatoplasty, preoperative and postoperative speech assessments, magnetic resonance imaging findings, and obstructive sleep apnea outcomes. The authors included 72 nonsyndromic patients who underwent pharyngeal flap surgery following cleft palate repair. The mean age at pharyngeal flap surgery was 10.6 ± 6.2 years. There was a significant improvement in the Pittsburgh Weighted Speech Score Hypernasality Component and the nasalance scores of oral syllables (p < 0.001). The obstructive sleep apnea rate after pharyngeal flap surgery was 6.9%. Compared to preoperatively, the velar angle was more acute (p < 0.001), the velar length was longer (p < 0.001), the distance of the velum tip to the posterior pharyngeal wall was shorter (p < 0.001), the size of velopharyngeal gap was narrower (p < 0.001), and the pharyngeal flap atrophied (p < 0.001) at 6 months postoperatively. The pharyngeal flap improved speech outcomes in patients with velopharyngeal insufficiency with a relatively low incidence of obstructive sleep apnea (6.9%). The velum is positioned more superiorly and posteriorly, and the size of the velopharyngeal gap is substantially reduced after pharyngeal flap surgery. In addition, the pharyngeal flap partially atrophied over time.


Social familiarity affects Diana monkey (Cercopithecus diana diana) alarm call responses in habitat-specific ways.
Male Diana monkeys produce loud and acoustically distinct alarm calls to leopards and eagles that propagate over long distances, much beyond the immediate group. Calling is often contagious, with neighbouring males responding to each other's calls, indicating that harem males communicate both to local group members and distant competitors. Here, we tested whether male Diana monkeys responding to each other's alarm calls discriminated familiar from unfamiliar callers in two populations in Taï Forest (Ivory Coast) and on Tiwai Island (Sierra Leone). At both sites, we found specific acoustic markers in male alarm call responses that discriminated familiar from unfamiliar callers, but response patterns were site-specific. On Tiwai Island, males responded to familiar males' eagle alarms with 'standard' eagle alarm calls, whereas unfamiliar males triggered acoustically atypical eagle alarms. The opposite was found in Taï Forest where males responded to unfamiliar males' eagle alarm calls with 'standard' eagle alarms, and with atypical eagle alarms to familiar males' calls. Moreover, only Taï, but not Tiwai, males also marked familiarity with the caller in their leopard-induced alarms. We concluded that male Diana monkeys encode not only predator type but also signaller familiarity in their alarm calls, although in population-specific ways. We explain these inter-site differences in vocal behaviour in terms of differences in predation pressure and population density. We discuss the adaptive function and implications of this behaviour for the origins of acoustic flexibility in primate communication.


Calcium-phospholipid interactions in secretory cells: a new perspective on stimulus-secretion coupling.
Recent evidence suggests that stimuli delivered to the cell surface may alter Ca availability by promotion membrane phospholipid turnover. Due to the importance of Ca in stimulus-secretion coupling, the study of membrane phospholipid turnover could provide valuable information on the cellular mechanisms of evoked secretion. In the adrenal cortex, Ca is an obligatory requirement for adrenocorticotropin (ACTH)-induced steroid production and release, and recent findings revealed the presence of a Ca-dependent phospholipase A2 localized to the surface of isolated feline adrenocortical cells. This phospholipase is activated by ACTH to promote the release of arachidonic acid from phospholipids and thereby stimulate prostaglandin formation. Further investigations into the fate of radiolabeled arachidonic acid described a rapid and specific turnover of arachidonic acid within a phosphatidylinositol (PI) pool that is independent of changes in de novo synthesis and is characterized as a Ca-dependent hydrolysis of PI, followed by a rapid, selective reacylation of lysoPI. A similar deacylation-reacylation reaction involving arachidonyl PI is also found in the rabbit neutrophil when challenged with the formyl-methionyl peptide, F-Met-Leu-Phe, or the Ca-selective ionophore A23187. The relevance of this reaction to secretory phenomena is indicated by its requirement for Ca, its rapid onset, and dose-response curves that paralleled those of the secretory response. The Ca-dependent activation of arachidonyl PI turnover triggered by the activation of membranous phospholipase A2 occupies a critical position in the train of events associated with the activation of the secretory process, and one or another of the products of this reaction-prostaglandins, arachidonic acid, and/or lysophospholipids-may participate in the cellular processes that accompany the discharge of secretory product.


[Sonography of the kidneys and urinary tract in infancy].
Sonography is the imaging method of choice in all diseases of the kidneys and urinary tract in infancy. The most important indications are all malformation syndromes, especially malformations of the urinary tract, urinary tract infections, space occupying lesions of the kidney, renal insufficiency, hematuria, arterial hypertension, abdominal pain and inherited kidney diseases.


Connexin32-containing gap junctions in Schwann cells at the internodal zone of partial myelin compaction and in Schmidt-Lanterman incisures.
In vertebrate peripheral nerves, the insulating myelin sheath is formed by Schwann cells, which generate flattened membrane processes that spiral around axons and form compact myelin by extrusion of cytoplasm and adhesion of apposed intracellular and extracellular membrane surfaces. Cytoplasm remains within the innermost and outermost tongues, in the paranodal loops bordering nodes of Ranvier and in Schmidt-Lanterman incisures. By immunocytochemistry, connexin32 (Cx32) protein has been demonstrated at paranodal loops and Schmidt-Lanterman incisures, and it is widely assumed that gap junctions are present in these locations, thereby providing a direct radial route for transport of ions and metabolites between cytoplasmic myelin layers. This study used freeze-fracture replica immunogold labeling to detect Cx32 in ultrastructurally defined gap junctions in Schmidt-Lanterman incisures, as well as in a novel location, between the outer two layers of internodal myelin, approximately every micrometer along the entire length of myelin, at the zone between compact myelin and noncompact myelin. Thus, these gap junctions link the partially compacted second layer of myelin to the noncompact outer tongue. Although these gap junctions are unusually small (average, 11 connexon channels), their relative abundance and regular distribution along the zone that is structurally intermediate between compact and noncompact myelin demonstrates the existence of multiple sites for unidirectional or bidirectional transport of water, ions, and small molecules between these two distinct cytoplasmic compartments, possibly to regulate or facilitate myelin compaction or to maintain the transition zone between noncompact and compact myelin.


Unicondylar Knee Arthroplasty in the U.S. Patient Population: Prevalence and Epidemiology.
Publications on the prevalence of unicompartmental knee arthroplasty in the United States using a single database may have underestimated the "true" number of cases performed, given that several unicondylar knee arthroplasty (UKA) patients are <65 years and have private insurance. The prevalence of UKA in elderly (≥65 years) and younger (<65 years) populations was evaluated using the 2002 to 2011 5% sample of the Medicare data (Part B) and the 2004 to June 2012 MarketScan Commercial and Medicare Supplemental databases, respectively. The prevalence of UKA was stratified by age, gender, census region, Charlson comorbidity index, Medicare buy-in status, and diagnosis. The annual rate of change in the UKA rate was examined using Poisson regression to evaluate temporal changes considering year as a covariate. A total of 5235 and 23,310 UKA procedures were identified from the 5% Medicare and MarketScan databases, respectively. The rates of UKA generally increased until 2008, after which there was a decline. In both cohorts, gender and year of operation were found to be significantly associated with UKA rate. Analysis of data obtained over the past few years revealed that males 55 to 64 years, 65 to 69 years, and 70 to 74 years were the only age-gender groups whose UKA rates appeared to be trending upward. From 2002 to 2011, the rate of UKAs performed in the United States has increased, and a significant proportion of the surgeries were performed in younger (<65 years) patients.


Psychedelics as anti-inflammatory agents.
Serotonin (5-hydroxytryptamine, 5-HT)2A receptor agonists have recently emerged as promising new treatment options for a variety of disorders. The recent success of these agonists, also known as psychedelics, like psilocybin for the treatment of anxiety, depression, obsessive-compulsive disorder (OCD), and addiction, has ushered in a renaissance in the way these compounds are perceived in the medical community and populace at large. One emerging therapeutic area that holds significant promise is their use as anti-inflammatory agents. Activation of 5-HT2A receptors produces potent anti-inflammatory effects in animal models of human inflammatory disorders at sub-behavioural levels. This review discusses the role of the 5-HT2A receptor in the inflammatory response, as well as highlight studies using the 5-HT2A agonist (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI] to treat inflammation in cellular and animal models. It also examines potential mechanisms by which 5-HT2A agonists produce their therapeutic effects. Overall, psychedelics regulate inflammatory pathways via novel mechanisms, and may represent a new and exciting treatment strategy for several inflammatory disorders.


Oral Trichogranuloma in an Asian 12-Year-Old Female With Trichotillomania.
Pilonidal sinus is an acquired chronic inflammatory condition associated with the penetration of hair fragments into the skin. In the pathogenesis of most of these cases, a traumatic event initiates the process allowing the introduction of the hairs into the skin. We report an unusual case of acquired pilonidal sinus as a consequence of the unconscious habit of chewing on the hairs in a 12-year-old girl. Although most commonly located in the gluteal cleft, it has been reported in several areas of the body (including face), but to the best of our knowledge, this is the first report in the oral cavity. Our case presented as a palatal and vestibular fistula in a patient who suffered from an undiagnosed peculiar form of hair pulling disorder that involved hair chewing but not trichophagia.


Major liver trauma.
Data are presented on nine patients in whom hepatic resection was performed for liver injury associated with multiple trauma. Perioperative hemodynamic homeostasis requires the support of the department of hematology, for supply of coagulation factors and platelet transfusions. Supplementary support in the postoperative period requires replacement of materials normally produced by the liver until normal liver function returns. Infection requires close attention for its successful management. Finally, with due regard to the attendant hematologic problems, we must still be prepared to perform extensive hepatic resection, if necessary.


Normal-law quantile phase filters for mode conversion in single-mode fibers applied to wavelength blockers.
We propose the definition of a new family of complex-amplitude filters. These filters are optimal for mode conversion in single-mode fibers and give rise to a large variety of spatial designs. Among them, we focus on a few that are easy to manufacture and implement, in particular, in an array shape, and present some technical advantages such as tolerance to positioning. In the second part, we discuss their implementations by using various technologies and the effect of some technical constraints on filter shape and phase distribution. Finally, we illustrate their uses in the case of a dynamic wavelength blocker within the frame of wavelength-division-multiplexing network systems.


Development and Use of Health-Related Technologies in Indigenous Communities: Critical Review.
Older Indigenous adults encounter multiple challenges as their age intersects with health inequities. Research suggests that a majority of older Indigenous adults prefer to age in place, and they will need culturally safe assistive technologies to do so. The aim of this critical review was to examine literature concerning use, adaptation, and development of assistive technologies for health purposes by Indigenous peoples. Working within Indigenous research methodologies and from a decolonizing approach, searches of peer-reviewed academic and gray literature dated to February 2016 were conducted using keywords related to assistive technology and Indigenous peoples. Sources were reviewed and coded thematically. Of the 34 sources captured, only 2 concerned technology specifically for older Indigenous adults. Studies detailing technology with Indigenous populations of all ages originated primarily from Canada (n=12), Australia (n=10), and the United States (n=9) and were coded to four themes: meaningful user involvement and community-based processes in development, the digital divide, Indigenous innovation in technology, and health technology needs as holistic and interdependent. A key finding is the necessity of meaningful user involvement in technology development, especially in communities struggling with the digital divide. In spite of, or perhaps because of this divide, Indigenous communities are enthusiastically adapting mobile technologies to suit their needs in creative, culturally specific ways. This enthusiasm and creativity, coupled with the extensive experience many Indigenous communities have with telehealth technologies, presents opportunity for meaningful, culturally safe development processes.


Open versus laparoscopic retroperitoneal lymph node dissection: assessing adequacy of dissection in a porcine model.
Laparoscopic retroperitoneal lymph node dissection (L-RPLND) is emerging as a viable alternative to traditional open retroperitoneal lymph node dissection (O-RPLND). Despite numerous reports confirming clinical oncologic equivalency between the two approaches, however, concerns still remain over the adequacy of laparoscopic dissection. We therefore sought to compare the completeness of dissection between O-RPLND and L-RPLND in a porcine model. Fourteen domestic swine were divided into two equivalent groups. Both groups underwent bilateral retroperitoneal lymph node dissection, approximating templates used in human dissection. In one group, the procedure was performed through an open midline incision, while the other group underwent completely laparoscopic dissection. Tissue was independently analyzed by a pathologist, who recorded lymph node yield based on microscopic evaluation. All animals in the L-RPLND group underwent successful procedures, without the need for conversion. Two open procedures were aborted because of hemorrhage. Mean lymph node yield from O-RPLND was 32, while the mean yield for L-RPLND was 29. This difference was not statistically significant (P=0.65). In the porcine model, L-RPLND is capable of providing a quality of dissection equivalent to that of O-RPLND, in terms of absolute lymph node yield on microscopic examination. The applicability of this data to human patients, however, may be limited by significant anatomic differences between the human and the pig. Further prospective comparison in human patients is critically needed.


Spectrum of Hybrid Cysts and Their Clinical Significance.
A hybrid cyst is a cutaneous cyst combining different types of keratinization of those seen in the folliculo-sebaceous-apocrine unit. Previous reports found that it may be occasionally associated with Gardner syndrome. This study aimed to clarify the pathologic findings and clinical significance of hybrid cyst based on case series observations. We retrospectively reviewed patients who fulfilled the pathological criteria of hybrid cyst from 2001 to 2015. The patient profiles, clinical presentations, pathological findings, and associated diseases were analyzed by reviewing the medical records and slides. A total of 71 hybrid cysts were confirmed over the study period. There were 12 pathologic variants. The most frequent variant was combined infundibular cyst and tricholemmal cyst (22 in 71 cases, 30%), followed by infundibular cyst and pilomatricoma (14 in 71 cases, 19%). There was no significant association between sex, age, or site and the pathological type of hybrid cyst. Neither extra-intestinal manifestation nor a family history of Gardner syndrome was found in any case. Hybrid cysts could contain a variety of combinations of components from the folliculo-sebaceous-apocrine unit. No clinical significance was found between demographics and the type of hybrid cyst. No association with Gardner syndrome was identified in this case series.


[Modern technologies in rehabilitation program for children with the lympho-glottal ring pathology with recurrent respiratory diseases].
A method of laser therapy is proposed as a stage of rehabilitation for children (220 preschool 3-6-year-olds) with chronic adenoiditis frequently ill with acute respiratory viral infection. Magnetolaser therapy (Rikta-01 unit) was given for 10 days twice a year. The efficacy of the treatment was assessed by activity of lysozyme, concentration of slgA of nasal secretion, nasocytogram. A 12-month follow-up confirmed a positive effect of laser therapy on immunity of the respiratory tract and clinical symptoms with reduction in the size of hypertrophic palatine tonsil.


Successful immunization of infants with and without maternal antibody by aerosolized measles vaccine. II. Vaccine comparisons and evidence for multiple antibody response.
In 4- and 5-month-old infants in whom the undiluted chick embryo fibroblast (CEF) Schwarz strain measles vaccine had a poor immunogenic effect, there was an increase in immunogenicity when the high sugar concentration was diminished without reference to added albumin. The human diploid cell (HDC) measles vaccine was still superior in this age group even in a lower concentration of the Ikić, Edmonston-Zagreb strain of virus. More aerosolized, HDC Ikić strain virus was required for high seroconversion rates in 4- and 5-month-old infants who had higher titers of prevaccination plaque-neutralizing (PN) antibodies. Some of these infants had a delayed immune response that was absent at six weeks but present at three months after vaccination. The data provided evidence that the PN and enzyme-linked immunosorbent assay techniques measured different antibodies that develop and persist in different ways in 4- to 5-month-old infants. The HDC lyophilized measles vaccine yielded unexpectedly high seroconversion rates after subcutaneous injection of 5,000 plaque-forming units (PFUs) in 4-, 5-, and 6-month-old infants: 69%, 89%, and 100% respectively, at 14 weeks. In 12- to 23-month-old infants there was seroconversion of 92% and 100% at six weeks after inhalation of an estimated 175 PFUs of the CEF vaccine and 375 PFUs of the HDC vaccine, respectively. Within six weeks after vaccination, the PN antibody titers were significantly higher with the CEF vaccine (geometric mean titer of 2,275) than with the HDC vaccine (geometric mean titer of 343).


Evaluation of focal choroidal excavation in the macula using swept-source optical coherence tomography.
To evaluate imaging findings of patients with focal choroidal excavation (FCE) in the macula using swept-source optical coherence tomography (SS-OCT) and correlate it clinically. Prospective observational case series. Eleven consecutive patients (12 eyes) with FCE were described. Data on demographics and clinical presentation were collected and imaging findings (including color photography, fundus autofluorescence imaging, fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and SS-OCT) were analyzed. The primary diagnosis was epiretinal membrane (two eyes), choroidal neovascularization (one eye), polypoidal choroidal vasculopathy (three eyes), central serous chorioretinopathy (one eye), and dry age-related macular degeneration (two eyes). Eleven out of 12 of the lesions were conforming. One presented with a non-conforming lesion that progressed to a conforming lesion. One eye had multiFCE and two had two overlapping choroidal excavations. Using the SS-OCT, we found the choroid to be thinned out at the area of FCE but sclera remained normal. The choroidal tissue beneath the FCE was abnormal, with high internal reflectivity and poor visualization of choroidal vessels. There was loss of contour of the outer choroidal boundary that appeared to be pulled inward by this abnormal choroidal tissue. A suprachoroidal space was noted beneath this choroidal tissue and the choroidal-scleral interface was smooth. Repeat SS-OCT 6 months after presentation showed the area of excavation to be stable in size. FCE can be associated with epiretinal membrane, central serous chorioretinopathy, and age-related macular degeneration. The choroid was thinned out in the area of FCE.


ICTV Virus Taxonomy Profile: Leishbuviridae 2023.
Leishbuviridae is a family of negative-sense RNA viruses with genomes of about 8.0 kb that have been found in protists. The leishbuvirid genome consists of three monocistronic RNA segments with open reading frames (ORFs) that encode a nucleoprotein (NP), a glycoprotein (GP), and a large (L) protein containing an RNA-directed RNA polymerase (RdRP) domain. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Leishbuviridae, which is available at ictv.global/report/leishbuviridae.


Is colour duplex sonography-guided temporal artery biopsy useful in the diagnosis of giant cell arteritis? A randomized study.
The aim of this study was to assess the usefulness of colour duplex sonography (CDS)-guided temporal artery biopsy (TAB) for the diagnosis of GCA in patients with suspected GCA. From September 2009 through December 2012, 112 consecutive patients with suspected GCA were randomized to undergo CDS-guided TAB or standard TAB. All patients underwent temporal artery physical examination and temporal artery CDS prior to TAB. CDS of the temporal artery was performed by the same ultrasonographer, who was unaware of the patient's clinical data, and all TABs were evaluated by the same pathologist. Seven patients in whom biopsy failed to sample temporal artery tissue were excluded from the analysis. Fifty patients were randomized to undergo CDS-guided TAB and 55 patients to standard TAB. Except for a younger age in patients who underwent standard TAB (P = 0.026), no significant differences were observed between the two groups. There were no significant differences in the frequencies of positive TAB for classic transmural inflammation (28% vs 18.2%) or for periadventitial small vessel vasculitis and/or vasa vasorum vasculitis (6% vs 14.5%) between the two groups. No significant differences in the frequency of positive TAB in the two groups were observed when we excluded the patients treated with glucocorticoids and when we stratified the patients of the two groups for the presence or absence of the halo sign. Our study showed that CDS-guided TAB did not improve the sensitivity of TAB for diagnosing GCA.


Diaphragm Muscle Thinning in Subjects Receiving Mechanical Ventilation and Its Effect on Extubation.
Diaphragm muscle weakness and atrophy are consequences of prolonged mechanical ventilation. Our purpose was to determine whether thickness of the diaphragm (TDI) changes over time after intubation and whether the degree of change affects clinical outcome. For this prospective, longitudinal observational study, we identified subjects who required mechanical ventilation and measured their TDI by ultrasonography. TDI was measured at baseline and repeated 72 h later and then weekly until the subject was either liberated from mechanical ventilation, was referred for tracheostomy, or died. The analysis was designed to determine whether baseline TDI and change in TDI affect extubation outcome. Of the 57 subjects who underwent both diaphragm measurements at 72 h, 16 died, 33 were extubated, and 8 underwent tracheostomy. Only 14 subjects received mechanical ventilation for 1 week, and 2 subjects received mechanical ventilation for 2 and 3 weeks. Females had significantly thinner baseline TDI (P = .008). At 72 h, TDI had decreased in 84% of subjects. We found no significant association between the rate of thinning and sex (P = .68), diagnosis of COPD (P = .36), current smoking (P = .85), or pleural effusion (P = .83). Lower baseline TDI was associated with higher likelihood of extubation: 12.5% higher for every 0.01-cm decrease in TDI (hazard ratio 0.875, 95% CI 0.80-0.96, P = .003). For every 0.01-cm decrease in TDI at 72 h, the likelihood of extubation increased by 17% (hazard ratio 0.83, 95% CI 0.70-0.99, P = .041). Although most of the subjects showed evidence of diaphragm thinning, we were unable to find a correlation with outcome of extubation failure. In fact, the thinner the diaphragm at baseline and the greater the extent of diaphragm thinning at 72 h, the greater the likelihood of extubation. Thickening ratio or other measurement may be a more reliable indicator of diaphragm dysfunction and should be explored.


Nonlinearity-induced synchronization enhancement in micromechanical oscillators.
An autonomous oscillator synchronizes to an external harmonic force only when the forcing frequency lies within a certain interval-known as the synchronization range-around the oscillator's natural frequency. Under ordinary conditions, the width of the synchronization range decreases when the oscillation amplitude grows, which constrains synchronized motion of micro- and nanomechanical resonators to narrow frequency and amplitude bounds. Here, we show that nonlinearity in the oscillator can be exploited to manifest a regime where the synchronization range increases with increasing oscillation amplitude. Experimental data are provided for self-sustained micromechanical oscillators operating in this regime, and analytical results show that nonlinearities are the key determinants of this effect. Our results provide a new strategy to enhance the synchronization of micromechanical oscillators by capitalizing on their intrinsic nonlinear dynamics.


Second Opinion Assessment in Diagnostic Mammography at a Breast Cancer Centre.
Purpose: The aim of this retrospective study was to evaluate the importance of second opinion assessment for diagnostic mammography and sonography in a breast cancer centre. Material and Method: We analysed a total of 374 diagnostic mammographies and sonographies. All patients had previously undergone mammography and sonography examination in different external clinics, and the findings had been classified according to the BI-RADS system. All patients underwent additional sonography investigation in the outpatient department of our university clinic with additional mammography where necessary. The final diagnosis (histological clarification in 316 cases, follow-up in 58 cases) was compared with the BI-RADS classification made by the external clinics and by the university clinic, and the correlation between their findings and the final diagnosis was analysed. Results: The final diagnosis yielded 146 benign lesions and 228 cancers. In 74 % of cases (277/374), the BI-RADS classification of the first assessment corresponded to that of the second assessment. 26/55 lesions (47 %) were upgraded at the second assessment from BI-RADS 3 to BI-RADS 4, and 71/186 findings (38 %) were downgraded at the second assessment from BI-RADS 4 to BI-RADS 3. The correlation between the initial diagnosis made in the external facilities and the final diagnosis was low (kappa: 0.263), but the correlation between the second opinion assessment and the final diagnosis was significantly (p < 0.001) higher (kappa: 0.765). The second assessment increased the sensitivity from 91 % (208/228) to 99 % (225/228) and the specificity from 32 % (46/146) to 74 % (108/146). 20 additional malignant lesions were only detected at the second assessment; however the second assessment also resulted in 3 additional false-negative findings. Surgical biopsy was prevented in 49 women after the second assessment. Conclusion: An independent second diagnostic evaluation can significantly improve the correlation between BI-RADS classification and the final diagnosis, resulting in a benefit for the patient.


Activating transcription factor 4 is critical for proliferation and survival in primary bone marrow stromal cells and calvarial osteoblasts.
Activating transcription factor 4 (ATF4) is essential for bone formation. However, the mechanism of its actions in bone is poorly understood. The present study examined the role for ATF4 in the regulation of proliferation and survival of primary mouse bone marrow stromal cells (BMSCs) and osteoblasts. Results showed that Atf4(-/-) cells display a severe proliferative defect as measured by multiple cell proliferation assays. Cell cycle progression of Atf4(-/-) BMSCs was largely delayed with significant G1 arrest. Expression of cyclin D1 was decreased both at the mRNA and protein level. A similar proliferation defect was observed in Atf4(-/-) calvarial periosteal osteoblasts when compared with wt control. Knocking down Atf4 mRNA by small interfering RNA in MC3T3-E1 subclone 4 preosteoblasts markedly reduced expression of cyclin D1 and cell proliferation. In contrast, overexpression of ATF4 increased cyclin D1 expression as well as cell proliferation in Atf4(-/-) BMSCs. In addition, apoptosis was significantly increased in Atf4(-/-) BMSCs and calvarial periosteal osteoblasts relative to wt controls. Taken together, these results for the first time demonstrate that ATF4 is a critical regulator of proliferation and survival in BMSCs and osteoblasts in vitro and in vivo.


Generation and validation of a zebrafish model of EAST (epilepsy, ataxia, sensorineural deafness and tubulopathy) syndrome.
Recessive mutations in KCNJ10, which encodes an inwardly rectifying potassium channel, were recently identified as the cause of EAST syndrome, a severe and disabling multi-organ disorder consisting of epilepsy, ataxia, sensorineural deafness and tubulopathy that becomes clinically apparent with seizures in infancy. A Kcnj10 knockout mouse shows postnatal mortality and is therefore not suitable for drug discovery. Because zebrafish are ideal for in vivo screening for potential therapeutics, we tested whether kcnj10 knockdown in zebrafish would fill this need. We cloned zebrafish kcnj10 and demonstrated that its function is equivalent to that of human KCNJ10. We next injected splice- and translation-blocking kcnj10 antisense morpholino oligonucleotides and reproduced the cardinal symptoms of EAST syndrome - ataxia, epilepsy and renal tubular defects. Several of these phenotypes could be assayed in an automated manner. We could rescue the morphant phenotype with complementary RNA (cRNA) encoding human wild-type KCNJ10, but not with cRNA encoding a KCNJ10 mutation identified in individuals with EAST syndrome. Our results suggest that zebrafish will be a valuable tool to screen for compounds that are potentially therapeutic for EAST syndrome or its individual symptoms. Knockdown of kcnj10 represents the first zebrafish model of a salt-losing tubulopathy, which has relevance for blood pressure control.


Miller Fisher syndrome and Guillain-Barré syndrome: dual intervention rehabilitation of a complex patient case.
Purpose: Guillain-Barré syndrome (GBS) presents with acute peripheral neuropathy leading to ascending motor and sensory deficits. Miller Fisher syndrome (MFS), a GBS variant, is characterized by ophthalmoplegia, ataxia, and areflexia. In unusual cases, MFS and GBS overlap. The purpose of this case report is to illustrate the effects of an aquatic and land-based physiotherapy (PT) intervention on a patient with MFS-GBS.Case Description: A 57-year-old male physician was diagnosed with complex regional pain syndrome following a quadriceps muscle tear. Within 1 month, the patient experienced evolving motor, sensory, autonomic, and cranial nerve dysfunction and was diagnosed with MFS-GBS.Interventions: Five months post-onset, a 7-week intensive PT program was initiated including aquatic and land-based interventions.Outcomes: Following completion, functional improvements were demonstrated on the 6 Minute Walk Test, Timed-Up-and-Go, 10 Meter Walk Test and Short Form-36. However, 6 weeks after program completion, the patient had a recurrence.Conclusion: PT intervention demonstrated improvement in functional outcomes for a patient with a diagnosis of MFS-GBS. Complex patients lacking recovery within 6 months may benefit from continued rehabilitation. Other intervention approaches may need to be considered, including aquatic therapy.


Associations of Dietary Intake on Biological Markers of Inflammation in Children and Adolescents: A Systematic Review.
In children and adolescents, chronic low-grade inflammation has been implicated in the pathogenesis of co- and multi-morbid conditions to mental health disorders. Diet quality is a potential mechanism of action that can exacerbate or ameliorate low-grade inflammation; however, the exact way dietary intake can regulate the immune response in children and adolescents is still to be fully understood. Studies that measured dietary intake (patterns of diet, indices, food groups, nutrients) and any inflammatory biomarkers in children and adolescents aged 2 to19 years and published until November 2020 were included in this systematic review, and were selected in line with PRISMA guidelines through the following databases: Academic Search Complete, CINAHL, Global Health, Medline COMPLETE and Web of Science-Core Collection. A total of 53 articles were identified. Results show that adequate adherence to healthful dietary patterns such as the Mediterranean diet, or food groups such as vegetables and fruit, or macro/micro nutrients such as fibre or vitamin C and E, are associated with decreased levels of pro-inflammatory biomarkers, mainly c-reactive protein (CRP), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α), whereas adherence to a Western dietary pattern, as well as intake of food groups such as added sugars, macro-nutrients such as saturated fatty acids or ultra-processed foods, is associated with higher levels of the same pro-inflammatory biomarkers. This is the first systematic review examining dietary intake and biological markers of inflammation in both children and adolescents. A good quality diet, high in vegetable and fruit intake, wholegrains, fibre and healthy fats ameliorates low-grade inflammation, and therefore represents a promising therapeutic approach, as well as an important element for disease prevention in both children and adolescents.


Physiological role of dietary energy in the sexual maturity: clues of body size, gonad development, and serum biochemical parameters of Chinese indigenous chicken.
Sexual maturity is a crucial factor in the formation and development of poultry reproductive capacity. The nutritional status has been confirmed to play an important role in the regulation of sexual maturity. To investigate the effect of dietary energy levels on sexual maturity in chicken, diets with 3 energy levels (group L: 2,573 kcal/kg, group C: 2,836 kcal/kg, group H: 3,122 kcal/kg) were implemented to feed Guangyuan Gray chickens. During this trial, body weight, body size, organ development, sexual maturity, reproductive performance and blood biochemical parameters were monitored. The earlier sexual maturity was observed in group H, as well as a heavier first egg weight, larger interpubic distance and higher total cholesterol (T-CHO) content at sexual maturity. The dietary energy levels had no significant effect on body weight at first egg and egg production at 300 d of age. Although dietary energy levels had a significant effect on body weight, comb length, tibia length and girth, abdominal fat weight, oviduct weight and length, T-CHO, triglyceride (TG) content and estradiol (E2) level during the rearing period. No significant difference of gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH) level among 3 groups was observed during the trial. The dietary energy levels had effects on mRNA expression of GnRH, estrogen receptor 1 (ESR1), estrogen receptor 2 (ESR2) in hypothalamus, gonadotropin inhibitory hormone receptor (GnIHR) in pituitary and luteinizing hormone receptor (LHR), ESR2 in ovary. The GnIHR/GnRHR ratio in pituitary was higher before sexual maturity and decreased at sexual maturity. The results of correlations analysis found that all the body size, carcass traits, serum biochemical parameters negatively correlated with age at first egg except for interpubic distance and serum blood glucose content. Collectively, dietary energy levels had effects on sexual maturity of chicken, which may be achieved by affecting body weight, gonad development, endocrine and the mRNA expression of genes related to hypothalamus-pituitary-gonad axis. These results further set our understanding of how dietary energy regulates sexual maturity.


The Effects of a 6-Week Strength Training on Critical Velocity, Anaerobic Running Distance, 30-M Sprint and Yo-Yo Intermittent Running Test Performances in Male Soccer Players.
The objectives of this study were to examine the effects of a moderate intensity strength training on changes in critical velocity (CV), anaerobic running distance (D'), sprint performance and Yo-Yo intermittent running test (Yo-Yo IR1) performances. two recreational soccer teams were divided in a soccer training only group (SO; n = 13) and a strength and soccer training group (ST; n = 13). Both groups were tested for values of CV, D', Yo-Yo IR1 distance and 30-m sprint time on two separate occasions (pre and post intervention). The ST group performed a concurrent 6-week upper and lower body strength and soccer training, whilst the SO group performed a soccer only training. after the re-test of all variables, the ST demonstrated significant improvements for both, YoYo IR1 distance (p = 0.002) and CV values (p<0.001) with no significant changes in the SO group. 30-m sprint performance were slightly improved in the ST group with significantly decreased performance times identified in the SO group (p<0.001). Values for D' were slightly reduced in both groups (ST -44.5 m, 95% CI = -90.6 to 1.6; SO -42.6 m, 95% CI = -88.7 to 3.5). combining a 6-week moderate strength training with soccer training significantly improves CV, Yo-Yo IR1 whilst moderately improving 30-m sprint performances in non-previously resistance trained male soccer players. Critical Velocity can be recommended to coaches as an additional valid testing tool in soccer.


Social and emotional wellbeing in Indigenous Australians: identifying promising interventions.
To review the empirical evidence that exists to support the delivery of the range of psycho-social interventions that have been implemented to improve social and emotional wellbeing (SEWB) in Aboriginal and Torres Strait Islander individuals and communities. A systematic review of the available literature, with relevant evaluations classified using the Maryland Scientific Methods Scale. Despite a substantial literature on topics relevant to SEWB being identified, only a small number of program evaluations have been published that meet the criteria for inclusion in a systematic review, making it impossible to articulate what might be considered evidence-based practice in this area. Examples of those programs with the strongest empirical support are outlined. The results are discussed in terms of the need to develop key indicators of improvement in SEWB, such that more robust evidence about program outcomes can be gathered. The diversity of the identified programs further suggests the need to develop a broader and over-arching framework from which to approach low levels of SEWB, drawing on the concepts of 'grief and loss' and 'healing' and how high levels of social disadvantage have an impact on service utilisation and outcomes. From a public health perspective, the pressing need to implement programs that have positive impacts on low levels of social and emotional well-being in Aboriginal and Torres Strait Islander communities in Australia seems clear.


Single dose streptozotocin-induced diabetes: considerations for study design in islet transplantation models.
Streptozotocin (STZ)-induced diabetes mellitus (DM) offers a very cost-effective and expeditious technique that can be used in most strains of rodents, opening the field of DM research to an array of genotypic and phenotypic options that would otherwise be inaccessible. Despite widespread use of STZ in small animal models, the data available concerning drug preparation, dosing and administration, time to onset and severity of DM, and any resulting moribundity and mortality are often limited and inconsistent. Because of this, investigators inexperienced with STZ-induced diabetes may find it difficult to precisely design new studies with this potentially toxic chemical and account for the severity of DM it is capable of inducing. Until a better option becomes available, attempts need to be made to address shortcomings with current STZ-induced DM models. In this paper we review the literature and provide data from our pancreatic islet transplantation experiments using single high-dose STZ-induced DM in NCr athymic nude mice with hopes of providing clarification for study design, suggesting refinements to the process, and developing a more humane process of chemical diabetes induction.


Patterning enzymes inside microfluidic channels via photoattachment chemistry.
We have developed a general method for photopatterning well-defined patches of enzymes inside a microfluidic device at any location. First, a passivating protein layer was adsorbed to the walls and floor of a poly(dimethylsiloxane)/glass microchannel. The channel was then filled with an aqueous biotin-linked dye solution. Using an Ar+/Kr+ laser, the fluorophore moieties were bleached to create highly reactive species. These activated molecules subsequently attached themselves to the adsorbed proteins on the microchannel walls and floor via a singlet oxygen-dependent mechanism. Enzymes linked to streptavidin or avidin could then be immobilized via (strept)avidin/biotin binding. Using this process, we were able to pattern multiple patches of streptavidin-linked alkaline phosphatase inside a straight microfluidic channel without the use of valves under exclusively aqueous conditions. The density of alkaline phosphatase in the patches was calculated to be approximately 5% of the maximum possible density by comparison with known standards. Turnover was observed via fluorogenic substrate conversion and fluorescence microscopy. A more complex two-step enzyme reaction was also designed. In this case, avidin-linked glucose oxidase and streptavidin-linked horseradish peroxidase were sequentially patterned in separate patches inside straight microfluidic channels. Product formed at the glucose oxidase patch became the substrate for horseradish peroxidase, patterned downstream, where fluorogenic substrate turnover was recorded.


Measuring cardiac index with a focused cardiac ultrasound examination in the ED.
Noninvasive technology may assist the emergency department (ED) physician in determining the hemodynamic status in critically ill patients. The objective of our study was to show that ED physicians can accurately measure cardiac index (CI) by performing a bedside focused cardiac ultrasound examination. A convenience sample of adult subjects were prospectively enrolled. Cardiac index, left ventricular outflow tract (LVOT) diameter, velocity time integral (VTI), stroke volume index, and heart rate were obtained by trained ED physicians and a certified cardiac sonographer. The primary outcome was percent of optimal LVOT diameter and VTI measurements as verified by an expert cardiologist. One hundred patients were enrolled, with obtainable CI measurements in 97 patients. Cardiac index, LVOT diameter, VTI, stroke volume index, and heart rate measurements by ED physician were 2.42 ± 0.70 L min(-1) m(-2), 2.07 ± 0.22 cm, 18.30 ± 3.71 cm, 32.34 ± 7.92 mL beat(-1) m(-2), and 75.32 ± 13.45 beats/min, respectively. Measurements of LVOT diameter by ED physicians and sonographer were optimal in 90.0% (95% confidence interval, 82.6%-94.5) and 91.3% (73.2%-97.6%) of patients, respectively. Optimal VTI measurements were obtained in 78.4% (69.2%-85.4%) and 78.3% (58.1%-90.3%) of patients, respectively. In 23 patients, the correlation (r) for CI between ED physician and sonographer was 0.82 (0.60-0.92), with bias and limits of agreement of -0.11 (-1.06 to 0.83) L min(-1) m(-2) and percent difference of 12.4% ± 10.1%. Emergency department ED physicians can accurately measure CI using standard bedside ultrasound. A focused ultrasound cardiac examination to derive CI has potential use in the management of critical ill patients in the ED.


Direct introduction of nitrogen and oxygen functionality with spatial control using copper catalysis.
Synthetic chemists have spent considerable effort optimizing the synthesis of nitrogen and oxygen containing compounds through a number of methods; however, direct introduction of N- and O-functionality remains challenging. Presented herein is a general method to allow for the simultaneous installation of N- and O-functionality to construct unexplored N-O heterocyclic and amino-alcohol scaffolds. This transformation uses earth abundant copper salts to facilitate the formation of a carbon-centered radical and subsequent carbon-nitrogen bond formation. The intermediate aminoxyl radical is terminated by an intramolecularly appended carbon-centered radical. We have exploited this methodology to also access amino-alcohols with a range of aliphatic and aromatic linkers.


Intraoperative image-directed dye marking of tumor margins.
The incorporation of interactive image guidance during intracranial tumor surgery offers the possibilities of reduced operative trauma, shorter operation time, greater precision, and an increased understanding of complex anatomy and pathology. A basic weakness with these systems though is that they cannot account for movement of target points due to brain shift by draining of CSF or removal of pathology during the operative procedure. We have developed a stereotactic (frameless) guided injector probe for marking the tumor boundary with dye injection in conjunction with a neuronavigation system. The device consisted of a rigid blunt hollow probe (2 mm dia.) with 4 small side holes at the tip. The catheter is mounted in a holder equipped with 3 LEDs supplying guidance information for the neuronavigation system. A small manual aliquoting pump delivers a measured amount of dye in each track. Isotonic methylene blue was injected in 6 to 8 tracks around the periphery of the tumor as determined by the contract ring in MR scans. The dye was injected using image-directed guidance before resection of the tumor was started (often with the dura intact). Tumor tissue could then be resected until the dye became visible at the tumor boundary. Identification of the dye in the tissue was enhanced with the use of the operating microscope. The 3-dimensional position of the dye track could be determined at the end of tumor resection and compared with its initial position giving a good estimate of local brain shift. The method has proved especially helpful for the resection of large gliomas allowing for a more radical operative result.


National Health Care Expenditures Associated With Disability.
In 2003, national disability-associated health care expenditures (DAHE) were $398 billion. Updated estimates will improve our understanding of current DAHE. The objective of this study was to estimate national DAHE for the US adult population and analyze spending by insurance and service categories and to assess changes in spending over the past decade. Data from the 2013-2015 Medical Expenditure Panel Survey were used to estimate DAHE for noninstitutionalized adults. These estimates were reconciled with National Health Expenditure Accounts (NHEA) data and adjusted to 2017 medical prices. Expenditures for institutionalized adults were added from NHEA data. National DAHE in total, by insurance and service categories, and percentage of total expenditures associated with disability. DAHE in 2015 were $868 billion (at 2017 prices), representing 36% of total national health care spending (up from 27% in 2003). DAHE per person with disability increased from $13,395 in 2003 to $17,431 in 2015, whereas nondisability per-person spending remained constant (about $6700). Public insurers paid 69% of DAHE. Medicare paid the largest portion ($324.7 billion), and Medicaid DAHE were $277.2 billion. More than half (54%) of all Medicare expenditures and 72% of all Medicaid expenditures were associated with disability. The share of health care expenditures associated with disability has increased substantially over the past decade. The high proportion of DAHE paid by public insurers reinforces the importance of public programs designed to improve health care for people with disabilities and emphasizes the need for evaluating programs and health services available to this vulnerable population.


Results of analyses and bacterial cultures of urine specimens obtained from clinically normal cats by three methods.
Six urine specimens were obtained from each of 6 male and 6 female cats in a 3-week period. The first and last specimens from each cat were obtained by cystocentesis, 2 were obtained by urethral catheterization, and 2 were caught during voiding stimulated by manual bladder compression. Quantitative urine cultures did not reveal bacteriuria in specimens obtained by cystocentesis, and urinary tract infection did not develop during the study. Bacteria were found in 3 (25%) of 12 urine specimens obtained by catheterization of males and in 1 (8%) of 12 specimens obtained by catheterization of females. Magnitude of bacteriuria in specimens obtained by catheterization was 10 to 1,000 organisms/ml. Bacteria also were found in specimens obtained during voiding. Each of 11 (100%) cleanly caught specimens obtained from males and 7 (58%) of 12 voided specimens from females contained bacteria. Magnitude of bacteriuria in voided specimens was usually 100 to 10,000 organisms/ml, but 3 voided specimens contained greater than 10,000 organisms/ml. Many bacteriuric specimens contained more than 1 type of organism; however, bacteria that might be suspected of causing urinary tract infections in cats were found frequently. Urinalyses were performed on 66 specimens. Completeness of urinalyses depended on the volume of specimens available, but results were normal except for evidence of hematuria in a few specimens obtained by cystocentesis or catheterization. Hematuria was usually mild and was attributed to hemorrhage caused by minor urinary tract trauma during urine collection.


Oral Health in the Population Assessment of Tobacco and Health Study.
Tobacco use is a well-established risk factor for multiple adverse oral conditions. Few nationally representative oral health data sets encompass the current diversity of tobacco and nicotine products. This investigation examines the validity of oral health measures in the Population Assessment of Tobacco and Health (PATH) Study to assess relationships between tobacco use and oral health. Cross-sectional data from PATH Study wave 4 (N = 33,643 US adults, collected 2016-2018) were used to obtain estimates for 6 self-reported oral conditions (e.g., bone loss around teeth, tooth extractions) and compared with analogous estimates from the National Health and Nutrition Examination Survey (NHANES) cycle 2017-2018 (N = 5,856). Within the PATH Study, associations were calculated between tobacco use status and lifetime and past 12-mo experience of adverse oral conditions using survey-weighted multivariable logistic regression. Nationally representative estimates of oral conditions between the PATH Study and NHANES were similar (e.g., ever-experience of bone loss around teeth: PATH Study 15.2%, 95% CI, 14.4%-15.9%; NHANES 16.6%, 95% CI, 14.9%-18.4%). In the PATH Study, combustible tobacco smoking was consistently associated with lifetime and past 12-mo experience of adverse oral health (e.g., exclusive cigarette smoking vs. never tobacco use, adjusted odds ratio [AOR] for loose teeth in past 12 mo: 2.02; 95% CI, 1.52-2.69). Exclusive smokeless tobacco use was associated with greater odds of loose teeth (AOR, 1.93; 95% CI, 1.15-3.26) and lifetime precancerous lesions (AOR, 3.85; 95% CI, 1.73-8.57). Use of other noncigarette products (e.g., pipes) was inconsistently associated with oral health outcomes. PATH Study oral health measures closely align with self-reported measures from NHANES and are internally concurrent. Observed associations with tobacco use and the ability to examine emerging tobacco products support application of PATH Study data in dental research, particularly to examine potential oral health effects of novel tobacco products and longitudinal changes in tobacco use behaviors.


Artificial intelligence in oncology.
Artificial intelligence (AI) has contributed substantially to the resolution of a variety of biomedical problems, including cancer, over the past decade. Deep learning, a subfield of AI that is highly flexible and supports automatic feature extraction, is increasingly being applied in various areas of both basic and clinical cancer research. In this review, we describe numerous recent examples of the application of AI in oncology, including cases in which deep learning has efficiently solved problems that were previously thought to be unsolvable, and we address obstacles that must be overcome before such application can become more widespread. We also highlight resources and datasets that can help harness the power of AI for cancer research. The development of innovative approaches to and applications of AI will yield important insights in oncology in the coming decade.


Audiological Outcomes of Type 1 Tympanoplasty Using Conchal Cartilage and Temporalis Fascia.
To compare the efficacy of conchal cartilage graft and temporalis fascia graft in Type 1 tympanoplasty in terms of graft uptake and hearing improvement. Descriptive study. Place and Duration of the Study: Department of Otolaryngology, Khyber Teaching Hospital, Peshawar, Pakistan, from January 2020 till December 2022. Using quota sampling, 2 groups were made i.e. conchal cartilage group (Group A) and temporalis fascia group (Group B). Total of 124 records were selected with 62 records from each group. Graft uptake rate and audiological outcomes were compared between the groups. Moreover, postoperative complication rate was also noted for each group. The graft uptake rates between Group A and B at 3rd month were compared postoperatively (98.39%, 93.55%, p=0.36). The difference between preoperative mean air-bone gap (ABG, 28.05 ± 2.19dB, 28.68 ± 2.38 dB, p=0.12) and postoperative mean ABG (13.35 ± 3.45, 14.47 ± 3.29, p=0.69) was also statistically not significant. However, the differences regarding audiological success rate between cartilage and fascia groups (96.77%, 82.25%, p=0.01) and average operating time (51.8 ± 2.1 vs. 43.5 ± 3.2 minutes, p=0.009) were significantly different. In chronic otitis media (COM) patients with subtotal perforations, endoscopic tympanoplasty using conchal cartilage or temporalis fascia as graft yielded comparable outcomes in terms of graft uptake, hearing improvement, and postoperative complications. However, using conchal cartilage, the procedure showed better audiological success rate. With temporalis fascia as graft, the procedure was performed in a shorter time. Chronic otitis media, Tympanoplasty, Temporalis fascia, Conchal cartilage, Subtotal perforation.


Multiple-Case Studies of Hand-on Breast Massage Techniques used by Breastfeeding Experts.
The aim of this study was to understand the hand-on breast massage techniques used by well-known experts in breastfeeding clinics. A qualitative multiple-case design was applied that involved a feasibility test. Four experts sampling qualitative data collected by observing participants and in individual interviews were analyzed by content analysis, linking data to the propositions, and cross-case pattern matching. This study explored differences within and between cases, and the possibilities of replicating findings across cases. Thirty-nine postpartum women participated voluntarily in the feasibility test, which investigated the usability of four massage techniques. The four techniques showed considerable similarities in terms of the application of stimulation to the breast base and increased flexibility of the wired flexible body, which was the core mechanism underlying the techniques. The breast management strategies were consistent with existing practice guidelines with the exception of using cold cabbage to control engorgement pain. There was insufficient scientific evidence for supporting the massage techniques used by the experts. All of the techniques showed 100% education completeness, but application rates were higher for self-control-oriented techniques. The massage techniques applied by experts in breastfeeding were based on hypotheses and self-control techniques are feasible to apply in practice.


A mechanistical model for the uptake of sulfonamides by bacteria.
The uptake of sulfonamides into bacterial cells was simulated by a dynamic model to estimate bioavailability and steady-state accumulation of sulfonamides in the cells. Uptake of sulfonamides is modeled as diffusion-like transport of the neutral molecule and the ionic species. Speciation outside and inside the cell depends on the extra- and intracellular pH and the pK(a)-value of the antibiotic active SO(2)NH moiety. The ratio between intra- and extracellular sulfonamide concentration is used as a measure for potential sulfonamide accumulation in bacterial cells. Simulated ratios are in good agreement with experimental data for various sulfonamides with pK(a2) values ranging from 5.0 up to 11.8. Sensitivity analyses indicate that intracellular sulfonamide concentration depend significantly on the degree of ionization in the cytoplasm and the surrounding medium. No accumulation in the cell occurs, if the external pH exceeds the intracellular pH. For sulfonamides with large pK(a)-values the internal activity equals the activity in the extracellular solution. Highest accumulation is reached if the pH gradient from inside to outside the cell is large, which depends on the bacterial pH-regulation mechanisms. The pH-dependent intracellular accumulation of various sulfonamides correlates well with their observed antibiotic effect on selected bacteria.


The Conformational Change of the L3 Loop Affects the Structural Changes in the Substrate Binding Pocket Entrance of β-Glucosidase.
β-glucosidase (Bgl) hydrolyzes cellobiose to glucose, thereby releasing non-reducing terminal glucosyl residues. Bgl is an essential enzyme belonging to the biomass-degrading enzyme family, which plays a vital role in enzymatic saccharification during biofuel production. The four loops above the Bgl substrate-binding pocket undergo a conformational change upon substrate recognition. However, the structural dynamism of this loop and how it is conserved among Bgl family members remain unknown. Herein, to better understand the four loops above the substrate-binding pocket of Bgl, four Bgl crystal structures in Thermoanaerobacterium saccharolyticum (TsaBgl) were determined at 1.5-2.1 Å. The L1, L2, and L4 loops of TsaBgl showed a rigid conformation stabilized by their neighboring residues via hydrogen bonds and hydrophobic interactions. The TsaBgl L3 loop showed relatively high flexibility and two different N-terminal region conformations. The conformational change in the TsaBgl L3 loop induced a change in charge and shaped at the substrate-binding pocket entrance. The amino acid sequences and structures of the TsaBgl L1-4 loops were compared with other 45 Bgl proteins, and a diversity of the L2 and L3 loops was observed. Differences in amino acids and lengths of Bgls L2-L3 loop induced differences in the conformation and structure of the Bgls substrate-binding pocket entrance. These findings expand our knowledge on the molecular function of the loops in the Bgl enzyme family.


Magnetic frustration, phase competition, and the magnetoelectric effect in NdFe3(BO3)4.
We present an element selective resonant magnetic x-ray scattering study of NdFe3(BO3)4 as a function of temperature and applied magnetic field. Our measurements show that the magnetic order of the Nd sublattice is induced by the Fe spin order. When a magnetic field is applied parallel to the hexagonal basal plane, the helicoidal spin order is suppressed and a collinear ordering, where the moments are forced to align in a direction perpendicular to the applied magnetic field, is stabilized. This result excludes a noncollinear spin order as the origin of the magnetically induced electric polarization in this compound. Instead our data imply that magnetic frustration results in a phase competition, which is the origin of the magnetoelectric response.


Exploring the outcomes and experiences of Black and White athletes following a sport-related concussion: a retrospective cohort study.
Young American athletes, at risk of sport-related concussion (SRC), represent many races; however, it is unknown how race may influence the experience and outcome of SRC. The authors' objective was to compare White and Black athletes' recovery and subjective experiences after SRC. A retrospective study was performed using the Vanderbilt Sports Concussion registry. Self-reported White and Black young athletes (ages 12-23 years) who had been treated for SRC between 2012 and 2015 were included. Athletes with learning disabilities or psychiatric conditions were excluded. Data were collected by electronic medical record review and phone calls to athletes and parents or guardians. The primary outcomes were as follows: 1) days to symptom resolution (SR), 2) days to return to school, and changes in 3) any daily activity (binary) and 4) sport behavior (binary). Secondary outcomes were changes (more, unchanged, or less) in specific activities such as sleep, schoolwork, and television time, as well as equipment (binary) or playing style (more reckless, unchanged, or less reckless) and whether the athlete retired from sport. Descriptive analyses, multivariable Cox proportional hazards models, and logistic regression were performed. The final cohort included 247 student-athletes (36 Black, 211 White). Black athletes were male (78% vs 58%) more often than White athletes, but both races were similar in age, sport, and medical/family histories. Black athletes more frequently had public insurance (33.3% vs 5.7%) and lived in areas with a low median income (41.2% vs 26.6%). After adjusting for age, sex, concussion history, insurance status, and zip code median income, Black athletes reached an asymptomatic status (HR 1.497, 95% CI 1.014-2.209, p = 0.042) and returned to school earlier (HR 1.522, 95% CI 1.020-2.270, p = 0.040). Black athletes were less likely to report a change in any daily activity than White athletes (OR 0.368, 95% CI 0.136-0.996, p = 0.049). Changes in sport behavior were comparable between the groups. Racial differences appear to exist in the outcomes and experience of SRC for young athletes, as Black athletes reached SR and return to school sooner than White athletes. Race should be considered as an important social determinant in SRC treatment.


DNA methylation mediates the association between breastfeeding and early-life growth trajectories.
The role of breastfeeding in modulating epigenetic factors has been suggested as a possible mechanism conferring its benefits on child development but it lacks evidence. Using extensive DNA methylation data from the ALSPAC child cohort, we characterized the genome-wide landscape of DNA methylation variations associated with the duration of exclusive breastfeeding and assessed whether these variations mediate the association between exclusive breastfeeding and BMI over different epochs of child growth. Exclusive breastfeeding elicits more substantial DNA methylation variations during infancy than at other periods of child growth. At the genome-wide level, 13 CpG sites in girls (miR-21, SNAPC3, ATP6V0A1, DHX15/PPARGC1A, LINC00398/ALOX5AP, FAM238C, NATP/NAT2, CUX1, TRAPPC9, OSBPL1A, ZNF185, FAM84A, PDPK1) and 2 CpG sites in boys (IL16 and NREP), mediate the association between exclusive breastfeeding and longitudinal BMI. We found enrichment of CpG sites located within miRNAs and key pathways (AMPK signaling pathway, insulin signaling pathway, endocytosis). Overall DNA methylation variation corresponding to 3 to 5 months of exclusive breastfeeding was associated with slower BMI growth the first 6 years of life compared to no breastfeeding and in a dose-response manner with exclusive breastfeeding duration. Our study confirmed the early postnatal period as a critical developmental period associated with substantial DNA methylation variations, which in turn could mitigate the development of overweight and obesity from infancy to early childhood. Since an accelerated growth during these developmental periods has been linked to the development of sustained obesity later in life, exclusive breastfeeding could have a major role in preventing the risks of overweight/obesity and children and adults through DNA methylation mechanisms occurring early in life.


Long-term Spartina alterniflora invasion simplified soil seed bank and regenerated community in a coastal marsh wetland.
The coastal wetland is easily invaded by alien species due to locating in the land and sea transitional area. As a potential driving regeneration force, the soil seed bank is vital to the community restoration and species diversity protection. To reveal the long-term Spartina alterniflora invasion impact on the soil seed banks and regenerated communities, we investigated the seed banks under the different vegetation types (S. alterniflora, Phragmites australis, Scirpus mariqueter, ruderal and unvegetated site) and soil depths (0-5 and 5-10 cm) in the coastal salt marsh wetland, Chongming island, eastern China. The results showed that the soil seed bank richness and species density under different vegetation types were higher than the aboveground vegetation, and those of 0-5 cm seed banks were higher than 5-10 cm, except for the unvegetated site. The species richness and S. alterniflora seed proportion in the seed banks under S. alterniflora communities (S.AS) were lower and larger respectively than those of other sites. The species composition between S.AS and the aboveground communities showed high similarity with aggregation phylogenetic structures in two soil depths. The seed bank variations at 0-5 and 5-10 cm depths were interpreted 3.03% and 2.25% by the aboveground communities, while 4.92% and 5.55% were interpreted by the soil microbial biomass. The SEM model explained 98.1% and 91.8% of the seed banks richness at the 0-5 cm depth and 5-10 cm depth, respectively, and explained 98.8% and 46.1% of the seed banks species density at the 0-5 cm depth and 5-10 cm depth, respectively. The aboveground vegetation biomass and abundance directly affected the 0-5 cm seed banks richness and species density, while its height and biomass only affected the 5-10 cm seed banks species density. The 0-10 cm soil depth microbial biomass indirectly affected the 0-5 cm seed banks richness and species density, while affected the 5-10 cm seed banks richness. Soil physical and chemical properties only indirectly affected the 0-5 cm seed banks species density. The results provided a reference for the ecological evaluation of the impacts of S. alterniflora invasion into the coastal salt marsh wetland of eastern China, and guidance for the protection and restoration of the native plant communities.


Effect of protein environment on electronically excited and ionized states of the green fluorescent protein chromophore.
The effect of the protein environment on the electronic structure of the green fluorescent protein (GFP) chromophore is investigated by QM/MM (quantum mechanics/molecular mechanics) calculations. The protein has very small effect on the excitation energy of the bright absorbing and the lowest triplet states of the anionic GFP chromophore, deprotonated 4-hydroxybenzylidene-2,3-dimethylimidazolinone (HBDI) anion, however, it increases vertical detachment energy from 2.5 eV (gas-phase deprotonated HBDI anion) to 5.0 eV (solvated protein). We also investigated possible existence of the charge-transfer-to-solvent (CTTS) states associated with the GFP chromophore. Although precursors of such states appear in cluster calculations, a tightly packed structure of the protein prevents the formation of the CTTS states in this system. Motivated by a recently discovered new type of photoconversion, oxidative redding, we characterized the redox properties of GFP. The computed standard reduction potential of the anionic form of GFP is 0.47 V (for the GFP(•) + 1e → GFP(-) reaction), and the reduction potential at physiological conditions (pH 7, T = 25 °C) is 0.06 V.


Two classes of mutant mammary tumor virus-infected HTC cell with defects in glucocorticoid-regulated gene expression.
We have isolated mutant derivatives of M1.54 (a mammary tumor virus [MTV]-infected rat hepatoma [HTC] cell line containing multiple integrated proviruses) that fail to express hormone-inducible cell surface viral glycoproteins. In wild-type M1.54, the synthetic glucocorticoid dexamethasone selectively stimulates the rate of synthesis of MTV RNA. In addition, dexamethasone is essential for posttranslational maturation of three of the four cell surface viral glycoproteins processed from the MTV glycosylated precursor polyprotein; the fourth mature species is produced constitutively. Two mutant phenotypes are described; each contains glucocorticoid receptors that are indistinguishable from the wild-type receptor with respect to hormone affinity, intracellular concentration, nuclear translocation efficiency, DNA-cellulose chromatography, and sedimentation rate. In one class, represented by the mutant line CR1, dexamethasone fails to stimulate the low basal rate of MTV gene transcription; surprisingly, hormonal regulation of tyrosine aminotransferase activity is also defective in CR1, whereas several other cellular responses to dexamethasone are normal. In the second class of mutants, represented by CR4, dexamethasone stimulates synthesis of MTV transcripts indistinguishable from those produced in M1.54, but only the constitutive cell surface viral glycoprotein is expressed. Thus, these mutants define two distinct and novel aspects of glucocorticoid regulated gene expression in HTC cells: CR4 contains a defect in a hormone inducible protein maturation pathway that acts on specific viral (and presumably cellular) precursor polypeptides, whereas the lesion in CR1 appears to affect the expression of a subset of the gene products normally under glucocorticoid control in M1.54.


Anti-inflammatory therapy in atherosclerosis.
Cardiovascular disease (CVD) is the leading cause of death. Although once considered merely as a lipid storage disease, studies indicate the role of inflammation in initiation and progression of atherosclerotic CVD, as well as the development of thrombotic complications. Despite significant advances in treatment of atherosclerosis, there still exists a residual risk for CVD-related morbidity and mortality. Even with optimal treatment, the rate of a new event after an index acute coronary syndrome event, such as myocardial ischemia or infarction, in the first three years has been reported to be as high as 20%. In the last decades, inflammation due to apoB-lipoproteins and other traditional risk factors, such as hypertension, diabetes and smoking, is accepted as a new target for CVD prevention. Up to now, several anti-inflammatory drugs have been tested for use in atherosclerosis. This review focuses on the current status of anti-inflammatory drug therapy for atherosclerotic CVD in humans.


Superior temporal gyrus thickness correlates with cognitive performance in multiple sclerosis.
Decreased cortical thickness that signifies gray matter pathology and its impact on cognitive performance is a research field with growing interest in relapsing-remitting multiple sclerosis (RRMS) and needs to be further elucidated. Using high-field 3.0 T MRI, three-dimensional T1-FSPGR (voxel size 1 × 1 × 1 mm) cortical thickness was measured in 82 regions in the left hemisphere (LH) and right hemisphere (RH) in 20 RRMS patients with low disease activity and in 20 age-matched healthy subjects that in parallel underwent comprehensive cognitive evaluation. The correlation between local cortical atrophy and cognitive performance was examined. We identified seven regions with cortical tissue loss that differed between RRMS and age-matched healthy controls. These regions were mainly located in the frontal and temporal lobes, specifically within the gyrus rectus, inferior frontal sulcus, orbital gyrus, parahippocampal gyrus, and superior temporal gyrus, with preferential left asymmetry. Increased cortical thickness was identified in two visual sensory regions, the LH inferior occipital gyrus, and the RH cuneus, implicating adaptive plasticity. Correlation analysis demonstrated that only the LH superior temporal gyrus thickness was associated with cognitive performance and its thickness correlated with motor skills (r = 0.65, p = 0.003), attention (r = 0.45, p = 0.042), and information processing speed (r = 0.50, p = 0.025). Our findings show that restricted cortical thinning occurs in RRMS patients with mild disease and that LH superior temporal gyrus atrophy is associated with cognitive dysfunction.


Smoking habits in a cohort of U.K. adolescents.
Active smoking is an increasing problem amongst U.K. teenagers. The smoking habits of a cohort of 14-16-year-olds were determined and the association between regular active smoking and domestic and social factors investigated. Current smoking habits of a cohort of 2289 14-16-year-olds were assessed using a simple postal questionnaire. Data concerning potential factors associated with active smoking were collected from questionnaire completed by parents. Nine hundred and sixty-nine (44.8%) children admitted to having smoked at some time, with 562 (30.0%) having smoked in the previous 12 months. Three hundred and six (14.1%) children were regular smokers and 158 (51.6% of regular smokers, 7.3% of total cohort) smoked daily. Age, number of other children in the household, parental smoking, smoking sibling(s) and living in a single parent household were all independently associated with regular smoking. Regular smoking was a significant problem amongst this cohort of teenagers. Living with other smokers, age, household size and living with one parent all predicted a regular smoking habit.


Use of Reverse Genetics for the Generation of Recombinant Influenza Viruses Carrying Nanoluciferase.
Influenza A (FLUAV) and influenza B (FLUBV) viruses are human and/or animal pathogens widely studied due to their importance to public health and animal production. Both FLUAV and FLUBV possess a genome composed of eight viral gene segments. For reverse genetics of influenza viruses, transcription of the mRNA for the viral proteins is typically done from a plasmid encoding an RNA polymerase II (pol II) promoter element upstream of cloned viral cDNA and expressed like host mRNA. On the other side, the synthesis of the negative-sense, single-stranded, uncapped vRNAs can be accomplished by the host's RNA polymerase I (pol I). The reverse genetics for influenza has allowed the manipulation of influenza genomes incorporating heterogeneous sequences into different segments of the influenza genome, such as reporter genes. In this chapter, we outline the protocol from the generation of reverse genetic plasmid that can be applied for the cloning of any of the segments of FLUAV or FLUBV. Furthermore, we describe a protocol for generating FLUAV or FLUBV recombinant viruses carrying Nanoluciferase (NLuc) in the PB1 gene using reverse genetics. Finally, we delineate a microneutralization protocol using FLUAV-NLuc or FLUBV-NLuc viruses optimized for the use of antibodies from different sources (mice, ferrets, avian, etc.), which provides a more sensitive, reliable, and avidity-independent method to assess the presence of neutralizing antibodies against FLUAV or FLUBV.


Circadian changes in the sweating-to-vasoconstriction interthreshold range.
Thermoregulatory defenses are characterized by thresholds, the core temperatures triggering each response. Core body temperature is normally maintained within the interthreshold range, temperatures between the sweating and vasoconstriction thresholds that do not trigger autonomic defenses. This range usually spans only some 0.2 degrees C, but it remains unknown whether similar precision is maintained during the circadian core temperature cycle of about 0.8 degrees C. Accordingly, we evaluated the interthreshold range at four times of the day. We studied ten male volunteers, each at 3 a.m., 8 a.m., 3 p.m., and 8 p.m. At least 12 h elapsed between tests, and the order was randomly assigned. At each study time, volunteers were warmed peripherally until sweating was observed. Skin temperature was subsequently kept constant while core temperature was decreased by central-venous infusion of ice-cold fluid until peripheral vasoconstriction was detected. The volunteers were not permitted to sleep during threshold determinations, although sleep was not otherwise controlled. The core temperature triggering an evaporative water loss of 40 g.m-2.h-1 identified the sweating threshold. Similarly, the vasoconstriction threshold was defined by the core temperature triggering the initial decreases in plethysmographic finger tip blood flow. The interthreshold range at 3 a.m. was twice that observed at the other study times (P<0.05). Our data suggest that autonomic control of body temperature is reduced at 3 a.m., even when sleep is denied. This result contradicts the general perception that circadian variation alters the thermoregulatory target temperature, but not precision of body temperature control.


A quality control method for detecting energy changes of medical accelerators.
A description is presented of a simple and sensitive method for detecting a change in the energy of the electrons bombarding the target of medical accelerators. This technique is useful for x-ray beams with end point energy in the range of 15.7 to 25 MeV. The method is based on the photoactivation of 160 and 14N in a small sample of ammonium nitrate. It was found that the ratio of the activity induced in the oxygen divided by that produced in the nitrogen can be used as a quality control technique to detect a change in the energy of the electrons that bombard the target of the accelerator. An electron energy change of the order of 0.2 MeV can be determined using this method.


Mechanisms of apoptosis induction and cell cycle regulation in irradiated leukemia U937 cells and enhancement by arsenic trioxide.
Apoptosis is a common mode of cell death after exposure of tumor cells to radiation and/or chemotherapy. The factors that determine the rate of induction of apoptosis are generally related to the functioning of cell cycle checkpoints. In the present study, we investigated the involvement of several genes in cell cycle redistribution and induction of apoptosis in U937 cells after low and high doses of radiation. Activation of CDC2 was observed after both low and high doses of radiation in U937 cells that underwent apoptosis. Expression of CDK2, CDC2 and cyclin A was induced rapidly in the process of radiation-induced apoptosis. In addition, we investigated the use of a clinically relevant dose of radiation to promote As2O3-induced apoptosis in U937 cells. We found that combining radiation and As2O3 may be a new and more effective means of cancer treatment.


Effect of diffusive and convective substrate transport on biofilm structure formation: a two-dimensional modeling study.
A two-dimensional model for quantitative evaluation of the effect of convective and diffusive substrate transport on biofilm heterogeneity was developed. The model includes flow computation around the irregular biofilm surface, substrate mass transfer by convection and diffusion, biomass growth, and biomass spreading. It was found that in the absence of detachment, biofilm heterogeneity is mainly determined by internal mass transfer rate of substrates and by the initial percentage of carrier-surface colonization. Model predictions show that biofilm structures with highly irregular surface develop in the mass transfer-limited regime. As the nutrient availability increases, there is a gradual shift toward compact and smooth biofilms. A smaller fraction of colonized carrier surface leads to a patchy biofilm. Biofilm surface irregularity and deep vertical channels are, in this case, caused by the inability of the colonies to spread over the whole substratum surface. The maximum substrate flux to the biofilm was greatly influenced by both internal and external mass transfer rates, but not affected by the inoculation density. In general, results of the present model were similar to those obtained by a simple diffusion-reaction-growth model.


Antioxidant properties of glutamine and its role in VEGF-Akt pathways in portal hypertension gastropathy.
To investigate the effects of glutamine on oxidative/nitrosative stress and the vascular endothelial growth factor (VEGF)-Akt-endothelial nitric oxide synthase (eNOS) signaling pathway in an experimental model of portal hypertension induced by partial portal vein ligation (PPVL). Portal hypertension was induced by PPVL. The PPVL model consists of a partial obstruction of the portal vein, performed using a 20 G blunt needle as a guide, which is gently removed after the procedure. PPVL model was performed for 14 d beginning treatment with glutamine on the seventh day. On the fifteenth day, the mesenteric vein pressure was checked and the stomach was removed to test immunoreactivity and oxidative stress markers. We evaluated the expression and the immunoreactivity of proteins involved in the VEGF-Akt-eNOS pathway by Western blotting and immunohistochemical analysis. Oxidative stress was measured by quantification of the cytosolic concentration of thiobarbituric acid reactive substances (TBARS) as well as the levels of total glutathione (GSH), superoxide dismutase (SOD) activity, nitric oxide (NO) production and nitrotyrosine immunoreactivity. All data are presented as the mean ± SE. The production of TBARS and NO was significantly increased in PPVL animals. A reduction of SOD activity was detected in PPVL + G group. In the immunohistochemical analyses of nitrotyrosine, Akt and eNOS, the PPVL group exhibited significant increases, whereas decreases were observed in the PPVL + G group, but no difference in VEGF was detected between these groups. Western blotting analysis detected increased expression of phosphatidylinositol-3-kinase (PI3K), P-Akt and eNOS in the PPVL group compared with the PPVL + G group, which was not observed for the expression of VEGF when comparing these groups. Glutamine administration markedly alleviated oxidative/nitrosative stress, normalized SOD activity, increased levels of total GSH and blocked NO overproduction as well as the formation of peroxynitrite. Glutamine treatment demonstrated to reduce oxidative damage but does not reduce angiogenesis induced by PH in gastric tissue, demonstrating a beneficial role for the PI3K-Akt-eNOS pathway.


Treatment and outcomes of UK and German patients with relapsed intracranial germ cell tumors following uniform first-line therapy.
We aimed to retrospectively assess treatments/outcomes, including the value of high-dose-chemotherapy and autologous-stem-cell-rescue (HDC + AuSCR) and re-irradiation, in a large, European patient-cohort with relapsed intracranial germ-cell-tumors (GCTs) receiving uniform first-line therapy, including radiotherapy as standard-of-care. Fifty-eight UK/German patients (48 male/10 female) with relapsed intracranial-GCTs [13 germinoma/45 non-germinomatous GCT (NGGCT)] treated 1996-2010 as per the SIOP-CNS-GCT-96 protocol were evaluated. For germinoma, six patients relapsed with germinoma and five with NGGCT (one palliative, one teratoma patient excluded). Five-year overall-survival (OS) for the whole-group (n = 11) was 55%. Four of six germinoma relapses and two of five relapsing with NGGCT were salvaged; patients were salvaged with either standard-dose-chemotherapy (SDC) and re-irradiation or HDC + AuSCR with/without re-irradiation. Of 45 relapsed NGGCT patients, 13 were excluded (three non-protocol adherence, five teratoma, five palliation). Five-year OS for the remaining 32 relapsed malignant NGGCT patients treated with curative intent was 9% (95%CI: 2-26%). By treatment received, 5-year OS for the 10 patients receiving SDC and 22 patients treated with intention for HDC + AuSCR was 0% (0-0%) and 14% (3-36%), respectively. The three relapsed NGGCT survivors had raised HCG markers alone; two received additional irradiation. Patients with relapsed germinoma had better 5-year OS than those with relapsed NGGCT (55 vs. 9%; p = 0.007). Patients with relapsed germinoma were salvaged both with SDC and re-irradiation or HDC + AuSCR with/without re-irradiation; both represent valid treatment options. Outcomes for malignant relapse following initial diagnosis of NGGCT were exceptionally poor; the few survivors received thiotepa-based HDC + AuSCR, which is a treatment option at first malignant relapse for such patients, with further surgery/irradiation where feasible.


Domain ontologies in software engineering: use of Protégé with the EON architecture.
Domain ontologies are formal descriptions of the classes of concepts and the relationships among those concepts that describe an application area. The Protégé software-engineering methodology provides a clear division between domain ontologies and domain-independent problem-solvers that, when mapped to domain ontologies, can solve application tasks. The Protégé approach allows domain ontologies to inform the total software-engineering process, and for ontologies to be shared among a variety of problem-solving components. We illustrate the approach by describing the development of EON, a set of middleware components that automate various aspects of protocol-directed therapy. Our work illustrates the organizing effect that domain ontologies can have on the software-development process. Ontologies, like all formal representations, have limitations in their ability to capture the semantics of application areas. Nevertheless, the capability of ontologies to encode clinical distinctions not usually captured by controlled medical terminologies provides significant advantages for developers and maintainers of clinical software applications.


Use of red blood cell fatty-acid profiles as biomarkers in cardiac disease.
The Omega-3 Index is defined as the percentage of eicosapentaenoic acid plus docosahexaenoic acid in red blood cell fatty acids, assessed by a standardized methodology. Better than fatty-acid compositions in other compartments, the Omega-3 Index represents a person's status in eicosapentaenoic acid plus docosahexaenoic acid. An Omega-3 Index less than 4% is associated with a tenfold risk for sudden cardiac death in comparison to an Omega-3 Index greater than 8%. Mechanisms of action are plausible and large-scale intervention studies in humans support causality. A low Omega-3 Index may also be a risk factor for coronary artery disease and for complications of congestive heart failure. Ongoing research will define the value of the Omega-3 Index as a risk factor and treatment parameter more precisely.